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The medical records of 600 consecutive women with a cesarean section will be reviewed.We will analyse the correlations between postcesarean section pain levels,analgesic consumption and; age,ethnic origin, parity,body habitus, smoking, breastfeeding, education,newborn in intensive care unit, primary/repeated operation,elective/emergency operation,junior/senior surgeon,type of anesthesia during operation.

The aim of this retrospective study is to find out if one or more of the following parameters has an impact on postcesarean section pain:age,ethnic origin, parity,body habitus, smoking, breastfeeding, education,newborn in intensive care unit, primary/repeated operation,elective/emergency operation,junior/senior surgeon,type of anesthesia during operation.

few studies has been done of serum levels Ca, P, PTH and vitamin D metabolites in patients receiving isotretinoin .In this study we measured serum levels Ca, P, PTH and vitamin D metabolites before and after treatment with isotretinoin for sever acne in 30 patients . the patients had no kown skeletal, endocrine ,renal and gastrointestinal disorders.

serum levels Ca, P, PTH and vitamin D metabolites before and after treatment with isotretinoin for sever acne

PROBLEM STATEMENT:~Current improvements of the design of the upper limb prosthesis include advanced technology in control systems and electronic circuitry that mimic human motion and improve function of the prosthesis. Often times these improvements require large amounts of power, circuitry and excess mass distally along the prosthesis that may require greater effort from the user. Poor function of an upper limb prosthesis may cause awkward compensatory motion. Aberrant movements, such as these compensatory movements are known to cause greater stress to remaining joints. Amputees are forced to decide if the extra function provided by the advanced electronics is worth carrying the extra mass which may cause fatigue, socket issues and greater stress on the remaining joints. An example is the wrist rotator component of an upper limb prosthesis which may allow greater function and reduce compensatory motion, but adds mass distally, potentially causing greater torques on remaining joints.~SYNOPSIS OF CURRENT LITERATURE:~Restricted motion and excess weight of an upper limb prosthesis have been documented as complaints among amputees [1], [2], [3], [4], [5], [6]. Through surveys Atkins et al. determined that amputees would like the wrist component of the prosthesis to perform more movements. This study also listed drinking from a glass and opening a door, top priorities among amputees [7]. This suggests that the wrist component on a prosthetic arm is important.~There are many examples throughout scientific literature showing how kinetic, kinematic and metabolic analyses of gait have lead to the improvement of lower limb prosthetic design criteria [8],[9]. In 2003, Twiste et al. conducted a literature review on rotation and translation of the anatomic joints during prosthetic gait. The abstract from this review mentions that more accurate kinematic gait analysis showing optimized gait patterns could help manufacturers design prosthetic components to mimic these patterns [9]. The effects of mass perturbations on lower limb amputees have been investigated to determine how inertial properties of a prosthesis should be evaluated [10].~There have also been studies involving upper limb motion, but the amount is limited. The range of motion of the upper limb of healthy and braced subjects performing activities of daily living have been recorded and analyzed [11],[12],[13]. These studies have looked at the effect of wrist position, but not on the mass of a wrist component.~GOALS OF THE STUDY:~There are two main goals of this study:~to determine the impact of an upper limb prosthesis without a wrist rotator on the compensatory motion and torques in the remaining joints during common tasks~to determine the impact of the location (distally or proximally) of a wrist rotator on a upper limb prosthesis on the compensatory motion during common tasks~HYPOTHESES:~There will be a statistically significant difference in range of motion of the upper limb joints between healthy subjects, braced subjects and upper limb amputees during four common tasks.~There will be a statistically significant difference in joint upper limb joint torques between healthy subjects, braced subjects and upper limb amputees during three common tasks.~There will be a statistically significant difference in upper limb angles and joint torques between mass added distally and mass added proximally during common tasks.~METHODS Participants Ten healthy adult volunteers with no history of upper limb injury will participate in this study. Five men and five women will participate. These ten subjects will make up the control group and then will be braced to simulate a below elbow prosthesis. Seven unilateral upper limb amputees will participate.~Testing Protocol An 8 camera infrared Vicon motion analysis system will be used for the collection and analysis of movement data. Nineteen spherical reflective markers will be placed on the boney landmarks of the upper limbs and torso of the subjects to describe segments or local coordinate systems.~A static trial will be collected for each subject to help determine the joint centers. Subject parameters such as body mass, height, and shoulder depth, wrist and hand thickness will be collected for use in calculations. Kinematic data will be collected at 120 Hz.~Subjects will be asked to complete four tasks:~Drinking from a cup~Opening a door~Lifting a 5 lb. box~Turning a steering wheel ( kinetic analysis of this task will be excluded)~The healthy subjects will complete each task during following interventions: (1) no intervention (2) braced restricting forearm and wrist motion, (3) braced with 96 g (mass of average prosthetic wrist rotator) added near the elbow, (4) braced with 96 g added near the wrist. The amputees will complete interventions (3) and (4) mentioned above without a wrist rotator but simulating the mass of one. Three trials will be collected for each experimental test condition and these trials will be averaged as a representative for each subject. The order of the tests will be randomly assigned for each subject.~Design of Experiment:~This study will look at the effects of the absence of wrist and forearm motion on shoulder, elbow and torso motion during four activities. This study will combine between-subject and within-subject analysis.~Independent factor (between subjects): restriction of wrist and forearm movement (simulating no wrist rotator component on prosthesis)~Levels:~Control group~Braced group - simulating a below elbow upper limb prosthesis~Prosthesis wearing group~Repeated factor (with-in subjects): added mass (simulating the mass of wrist rotator)~Levels:~No added mass of a wrist rotator~Mass of a wrist rotator added proximally (near elbow)~Mass of a wrist rotator added distally (near wrist)~A two-way analysis of variance with one repeated measure will be used to analyze the main effects and the interaction effects.~Data Processing~Shoulder, elbow and torso motions and torques will be computed using a program written in Vicon Bodybuilder language. The positions of the markers placed on the subject will be digitized and torso, upper arm, lower arm and hand segments will be determined. Euler angles will be computed. Inverse dynamics and anthropometrics will be used to compute forces and torques. The following outcome measures will be compared:~Shoulder abduction and flexion~Elbow flexion~Torso bending (L/R)~Shoulder joint force and torque~Elbow joint force and torque~The maximum, minimum and range of these outcome measures will be compared between subjects and with-in subjects.~PREDICTED RESULTS/DISCUSSION~Drinking from a cup:~Braced and prosthesis wearing groups will have greater shoulder abduction to compensate for the lack of forearm rotation and wrist extension.~Adding the mass (wrist rotator) distally will cause a greater force and torque at the elbow. This increase of forces at the elbow will be greatest in the amputee group due to possible injury to the brachialis at its insertion on the tuberosity of the ulna.~Opening a door:~Braced and prosthesis wearing groups will have greater shoulder abduction to compensate for the lack of forearm rotation and wrist extension. These groups may also compensate by the bending the trunk instead of increasing shoulder abduction.~Due to the increased shoulder range of motion in the coronal plane, the braced and prosthesis wearing group will have a greater torque at the shoulder joint. This increase of shoulder joint torque will increase when the mass (wrist rotator) is added distally due to the increase in the lever arm.~Lifting a 5 lb. box:~This task will require minimal wrist deviation, wrist flexion/extension and minimal forearm rotation. It is included in this study because it is a bilateral task~Braced and prosthesis wearing groups will greater shoulder abduction and lesser shoulder flexion due to the limitations of the forearm and wrist.~Shoulder and elbow joint forces and torques will be greater on the sound hand for the amputee group because they will used the prosthesis only as a guide to the task. However, the opposite could occur.~Turning a steering wheel:~Braced and prosthesis wearing groups will have greater shoulder abduction to compensate for the lack of wrist flexion and extension. However, compensation could also occur in trunk bending.~For this task the amputee subjects will first complete it with a sound arm and then the prosthesis to determine where compensation occurs.~CONTRIBUTIONS This work will provide many contributions to the biomechanics field and prosthetic design field. One important aspect of studying human maladies is to have a set of control data to use for comparison. Documenting kinematic data of the upper limb during four common tasks will allow for a comparison when studying many upper limb problems or injuries.~This work will help determine if location of new components should be considered in design, fitting and instruction of the upper limb prosthesis. It may also help to bridge the gap between the technological innovation of the engineering field and the clinical astuteness of the prosthetists that are in contact with the end users on a daily basis.~REFERENCES~S.C. Jacobsen, D.F. Knutti, R.T. Johnson and H.H. Sears, Development of the Utah artificial arm, IEEE Trans.Biomed.Eng., vol. 29, pp. 249-269, Apr. 1982.~J.E. Uellendahl, Upper extremity myoelectric prosthetics, Phys.Med.Rehabil.Clin.N.Am., vol. 11, pp. 639-652, Aug. 2000.~C.M. Light, P.H. Chappell, B. Hudgins and K. Engelhart, Intelligent multifunction myoelectric control of hand prostheses, J.Med.Eng.Technol., vol. 26, pp. 139-146, Jul-Aug. 2002.~P.J. Kyberd, D.J. Beard and J.D. Morrison, The population of users of upper limb prostheses attending the Oxford Limb Fitting Service, Prosthet.Orthot.Int., vol. 21, pp. 85-91, Aug. 1997.~W. Daly, Upper extremity socket design options, Phys.Med.Rehabil.Clin.N.Am., vol. 11, pp. 627-638, Aug. 2000.~H.H. Sears and J. Shaperman, Proportional myoelectric hand control: an evaluation, Am.J.Phys.Med.Rehabil., vol. 70, pp. 20-28, Feb. 1991.~D.J. Atkins, Heard D. and W.H. Donovan, Epidemiologic Overview of Individuals with Upper-Limb Loss and Their Reported Research Priorities, JPO, vol. 8, pp. 2-11, 1996. 1996.~J.S. Rietman, K. Postema and J.H. Geertzen, Gait analysis in prosthetics: opinions, ideas and conclusions, Prosthet.Orthot.Int., vol. 26, pp. 50-57, Apr. 2002.~M. Twiste and S. Rithalia, Transverse rotation and longitudinal translation during prosthetic gait--a literature review, J.Rehabil.Res.Dev., vol. 40, pp. 9-18, Jan-Feb. 2003.~R.W. Selles, J.B. Bussmand, L.M. Klip, B. Speet, A.J. Van Soest, H.J. Stam, Adaptations to Mass Perturbations in Transradial Amputees: Kinetic or Kinematic Invariance?, Arch. Phys. Med. Rehabil., vol. 85, pp. 2046-2052, Dec. 2004.~A. Murgia, P.J. Kyberd, P.H. Chappell and C.M. Light, Marker placement to describe the wrist movements during activities of daily living in cyclical tasks, Clin.Biomech.(Bristol, Avon), vol. 19, pp. 248-254, Mar. 2004.~R. Safaee-Rad, E. Shwedyk, A.O. Quanbury and J.E. Cooper, Normal functional range of motion of upper limb joints during performance of three feeding activities, Arch.Phys.Med.Rehabil., vol. 71, pp. 505-509, Jun. 1990.~J.S. Landry, Optimal Fixed Wrist Alignment For Below-Elbow, Powered , Prosthetic Hands, pp. 1-80, 2000. 2000.

Current improvements of the design of the upper limb prosthesis include advanced technology in control systems and electronic circuitry that mimic human motion and improve function of the prosthesis. Often times these improvements require large amounts of power, circuitry and excess mass distally along the prosthesis that may require greater effort from the user. Poor function of an upper limb prosthesis may cause awkward compensatory motion. Aberrant movements, such as these compensatory movements are known to cause greater stress to remaining joints. Amputees are forced to decide if the extra function provided by the advanced electronics is worth carrying the extra mass which may cause fatigue, socket issues and greater stress on the remaining joints. An example is the wrist rotator component of an upper limb prosthesis which may allow greater function and reduce compensatory motion, but adds mass distally, potentially causing greater torques on remaining joints.~GOALS OF THE STUDY:~There are two main goals of this study:~to determine the impact of an upper limb prosthesis without a wrist rotator on the compensatory motion and torques in the remaining joints during common tasks~to determine the impact of the location (distally or proximally) of a wrist rotator on a upper limb prosthesis on the compensatory motion during common tasks~HYPOTHESES:~There will be a statistically significant difference in range of motion of the upper limb joints between healthy subjects, braced subjects and upper limb amputees during four common tasks.~There will be a statistically significant difference in joint upper limb joint torques between healthy subjects, braced subjects and upper limb amputees during three common tasks.~There will be a statistically significant difference in upper limb angles and joint torques between mass added distally and mass added proximally during common tasks.

The MediventRTX portable lightweight respirator (MRTX) provides noninvasive respiratory support using biphasic extrathoracic ventilation via a cuirass fitted around the patient's chest. The aim of the study is to evaluate the efficacy of the MRTX during dental treatment under deep sedation in comparison with the conventional treatment where children are only under monitor and only intervention is done when required. Twenty healthy children (ASA1) will wear the cuirass. PO2 saturation and ETCO2 will be recorded as a baseline. Half of the children will be ventilated (with similar values to those of physiologic respiration) and the other half will not. The reason of the ventilation is to prevent apnea and high values of PCO2 due to superficial and not efficient breathing. An anesthesiologist is routinely present during treatment under deep sedation. After the child would be deep sedated, he/she will be connected to the cuirass that should be tightly fitted around the patient's chest. The cuirass consists of a clear, flexible plastic enclosure surrounding the chest and abdomen. Its borders are covered by a soft foam rubber, which creates an airtight seal around the patient. By choosing the appropriate cuirass size, the apparatus is capable of ventilating a wide range of different-sized subjects, from infants to the obese adult. The cuirass is connected to a computerized power unit by a wide-bore tube and the respiratory parameters are controlled by a feedback mechanism between the two. The power unit works by creating cyclic pressure changes inside the cuirass. The negative pressure (vacuum) creates chest expansion-inhalation. The positive pressure creates chest compression-exhalation. Thus, both inspiratory and expiratory phases are actively controlled, and the chest is oscillated around a variable negative baseline pressure. The system was found to be effective in a variety of clinical settings, with pressures of -25 to +15 cm H2O, inspiratory/expiratory (I/E) ratios of 1/1 to 1/3, and frequencies of 60 to 150 cpm~The study is blind, since the anesthesiologist and the dentist would not know if the cuirass of the child is connected to the MRTX or not:~Group 1- 10 children with the cuirass will be connected to the MRTX and artificially ventilated at pressures of (-12/+5) at a rate of 20 per minute, and PO2 and ETCO2 will be recorded every 5 minutes.~Group 2- 10 children with the cuirass will not be connected to the MRTX, but the machine will work at the same condition. Same records of PO2 and ETCO2 will be registered.

The MRTX portable lightweight respirator (MRTX) provides noninvasive respiratory support using biphasic extrathoracic ventilation via a cuirass fitted around the patient's chest.The aim of the study is to evaluate the efficacy of the MRTX during dental treatment under deep sedation in comparison with the conventional treatment where children are only under monitor and only intervention is done when required.Twenty healthy children (ASA1) will wear the cuirass. PO2 saturation and ETCO2 will be recorded as a baseline. Half of the children will be ventilated (with similar values to those of physiologic respiration) and the other half will notThe study is blind, since the anesthesiologist and the dentist would not know if the cuirass of the child is connected to the MRTX or not:~Group 1- 10 children with the cuirass will be connected to the MRTX and artificially ventilated at pressures of (-12/+5) at a rate of 20 per minute, and PO2 and ETCO2 will be recorded every 5 minutes.~Group 2- 10 children with the cuirass will not be connected to the MRTX, but the machine will work at the same condition. Same records of PO2 and ETCO2 will be registered.

The menopause implies the permanent cessation of menstrual bleeding. In western medicine, this is associated either with the spontaneous failure of normal ovarian function, or it may also result from surgical removal of the ovaries or as a consequence of chemotherapy or radiotherapy. In western medicine, the usual treatment of the menopause is the use of oestrogen replacement therapy. However, treatment with oestrogen may result in unwanted side effects such as breast soreness and nausea. In addition, the long-term safety of oestrogen treatment has not been established. Oestrogen is therefore a valuable treatment for the menopause, but it is not without side effects. It remains to be seen whether Chinese Medicine as described in this proposal can prove to be an effective, safe and well tolerated treatment for the menopause. Dang Gui (Radix Angelicae Sinensis) is one Chinese herb that is recommended for the treatment of menopausal symptoms. Huang Qi is also used in the treatment of the menopausal symptoms to tonify Qi. We have now shown a beneficial effect of Danggui Buxue Tang on vasomotor symptoms in postmenopausal Chinese women (Re: CREC Ref. No. CRE-2002.152-T). However, we could not show a difference in the reduction in severity of symptoms between Danggui Buxue Tang and placebo. We now wish to confirm our initial findings, and we hope to obtain more reliable data by (1) only including women who have never used any type of treatment for their menopause and (2) by recruiting women who have more severe symptoms of the menopause.~Chinese Herbal Medicines containing Dang Gui and Huang Qi have been used for many years to treat menopausal women. There are few data on possible adverse effects of treatment with Chinese Herbal Medicine containing Dang Gui as well as Huang Qi..~The objective of present study is to investigate the dose response relationship to assess an optimal dose suitable for clinical use. The trial will be designed as a multiple-dose escalation clinical trial to obtain accurate information on the efficacy and safety when used for menopausal women. Since previous study has already confirmed that the dose used was efficacious, the main purpose of the study is to look for an optimal dose for the treatment of menopausal symptoms.

Main purpose of the study is to look for an optimal dose for the treatment of menopausal symptoms with the Chinese Herbal Medicines containing Dang Gui and Huang Qi.

The primary objective of this study is to describe the effect of a single 30 mg/kg or 100 mg/kg intravenous (IV) dose of Motavizumab compared to placebo on study drug levels and viral load as measured by cultivatable virus and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in the upper respiratory tract in previously healthy children ≤12 months of age who are hospitalized with lower respiratory tract illness.

The primary objective of this study is to describe the effect of a single dose of medication compared to placebo in the upper respiratory tract in previously healthy children less than or equal to 12 months of age who are hospitalized with lower respiratory tract illness.

Cardiovascular disease is the commonest cause of morbidity and mortality in chronic dialysis patients, including those treated with CAPD (Continuous Ambulatory Peritoneal Dialysis) [1]. Uncontrolled arterial hypertension in ESRF leads to progression of LVH, which is a strong predictor for coronary events, CHF and mortality [2]. Fluid overload is a major factor in the pathogenesis of arterial hypertension in CAPD patients [3]. Therefore, interventions to optimize volume status, and hence blood pressure, are considered central in the management of such patients. Such therapies include restricting dietary sodium and water intake, use of diuretics in patients with residual renal function and optimization of peritoneal ultrafiltration with sodium and water removal [1]. As shown in the EAPOS Study, peritoneal ultrafiltration was important predictor of mortality [4].~Peritoneal fluid and salt removal can be increased by using a more hypertonic dialysis fluid using glucose as osmotic agent. Consistent use of hypertonic glucose solutions may damage peritoneal membrane and may also lead to increased systemic absorption of glucose with subsequent hyperglycemia, increased thirst and excessive water drinking. Concerns about the role of glucose in deterioration of peritoneal membrane function have been supported in recent studies [5]. Generally, the evolution of peritoneal membrane properties over time is characterized by a progressive increase in small solute transport, leading to higher glucose absorption rate from peritoneal fluid and loss of ultrafiltration capacity [6]. Such a high peritoneal transport status is associated with less peritoneal fluid removal, overhydration, hypertension and LVH. High peritoneal transport status is a risk factor of mortality in CAPD patients [7].~In recent years, there has been an increasing focus on association between inflammation, increased oxidative stress and high peritoneal transport rate and their relation to mortality in CAPD patients [8 ]. Inflammation has been shown to increase a peritoneal transport rate in CAPD patients [8]. Both inflammation and increased oxidative stress may impact to inadequate fluid removal. The exact mechanism of this phenomenon is not fully understood.~Several experimental and clinical studies showed that increased oxidative stress in dialysis patients may be due to inhibition of nitric oxide (NO) synthesis by ADMA (Asymmetric Dimethylarginine ), known to be endogenous inhibitor of NO synthetase [9]. ADMA may be significantly reduced by dialysis [10]. Metabolism of ADMA is primarily by the enzyme DDAH , which activity is decreased by inflammation, oxidative stress, diabetes mellitus and hypercholesterolemia [11]. It was proposed that circulating ADMA may be one mechanism accounting for the resistant hypertension and fluid overload in dialysis patients [11].~Based on current knowledge, treatment aimed at reducing oxidative stress should decrease ADMA levels [11], and it is logical to suggest that such a therapy might improve BP control and fluid status in CAPD patients. In our opinion, it is worth to check an ability of antioxidant therapy to produce a favorable effect on biological properties of peritoneal membrane. One preliminary study on effect of antioxidant Vitamin E showed a small beneficial effect on ADMA in chronic kidney disease [12].~N-Acetylcysteine (NAC) is an active antioxidant proved to be safe and beneficial in hemodialysis patents [13]. In our recent study, NAC effectively reduced the ototoxic effect of gentamicin in chronic hemodialysis patients [14].~The aim of our study is to investigate the effect of N-acetylcysteine on peritoneal small solute clearance and removal of salt and water in prevalent CAPD patients.

The aim of our study is to investigate the effect of N-acetylcysteine on peritoneal small solute clearance and removal of salt and water in prevalent CAPD patients.

Phase1 study of GSK1325760A~- A double blind, single center, randomised, placebo-controlled, partially crossover, single dose study to investigate the safety, tolerability, pharmacokinetics and to assess the effect of food on pharmacokinetics of ascending oral doses of GSK1325760A in healthy Japanese male subject -

To investigate the safety, tolerability, pharmacokinetics and the effect of food on pharmacokinetics after single oral administrations of GSK1325760A

Explorative, single-center, randomized, open label, 4-way crossover study to evaluate the pharmacokinetics and pharmacodynamics of different doses of spray-dried recombinant human insulin powder for inhalation administered via a dry powder uinhalation device compared with subcutaneously administered regular human insulin in healthy male volunteers under the conditions of a eugycemic clamp.

Evaluation of the pharmacokinetics and pharmacodynamics of different doses of spray-dried recombinant human insulin powder for inhalation administered via a dry powder uinhalation device compared with subcutaneously administered regular human insulin in healthy male volunteers under the conditions of a eugycemic clamp.

After renal transplantation, caused by ischemia or rejection, often renal transport processes are disturbed. These dysfunctions which are similar to the Fanconi syndrome as well as renal tubular acidosis occur in the early phase after transplantation. Irreversible injuries develop caused by nephrotoxicity of immunosuppressants and renal transplant artery stenoses. Although this has impact on clinical follow up and prognosis of the transplant, up to now, it still has to be clarified by which mechanisms the tubular transport processes are impaired.~In an animal model, we demonstrated first, that expression of membrane proteins is specifically modulated early after transplantation, indicating that changes in expression and function in these models are not due to general necrosis or apoptosis. Second, our results differ from data obtained after ischemia / reperfusion. Third, the regulatory pattern seems not to be the consequence of a systemic effect. We suppose that changes in expression of transporters and receptors after transplantation and rejection are continuously modulated, which may influence the prognosis of the graft. The data suggest that transplantation with acute rejection leads to ischemia-independent changes in the regulation of transporters along the nephron (Velic A, Gabriëls G, Hirsch JR, Schröter R, Edemir B, Paasche S, Schlatter E. Acute rejection after rat renal transplantation leads to downregulation of Na+ and water channels in the collecting duct. Am J Transplant. 2005, 5: 1276-85. Velic A, Hirsch JR, Bartel J, Thomas R, Schröter R, Stegemann H, Edemir B, August C, Schlatter E, Gabriëls G: Renal transplantation modulates expression and function of receptors and transporters of rat proximal tubules. J Am Soc Nephrol. 2004, 15: 967-77).~By means of microarray analysis we examined the expression of genes after renal transplantation in rats. Of the about 18.000 genes, in the model of acute rejection more than 55% of the genes were changed in their expression compared to controls, while transplantation without rejection only induced a change in expression of 30% of the genes. With rejection, about 50% of these genes were upregulated and about 50 % downregulated.~The regulated genes were classified in different groups. An essential part of the genes upregulated with rejection, as expected, point to a massive immune response. With rejection, a large amount of the genes coding for proteins with transport activity or proteins involved in metabolism are downregulated (e.g. amino acid transport, glucose transport, K+-, Ca++- and phosphate transport, transport of water, pH regulation). It was shown that, with rejection, signal transduction pathways involved in protein catabolism and immune response are upregulated.~By the present study in renal biopsies of about 200 transplanted individuals with acute rejection or chronic transplant nephropathy, we intend to examine the regulation of transport systems and regulatory factors during a period of two years. Our hypothesis is that the activity of transporters along the nephron is changed with renal transplantation, acute rejection reaction, or chronic transplant nephropathy. We intend to investigate underlying mechanisms in renal biopsy specimens obtained from patients because of acute rejection reaction or chronic transplant nephropathy.~The study has been designed to analyze whether the renal transport system factors we found to be differentially regulated in rats are regulated similarly with transplant rejection or transplant nephropathy in man.~The findings obtained by these studies also are indispensable regarding a plain comprehension of the development of tubule dysfunction after renal transplantation in man. The examination of the material serves to explore basic pathophysiological mechanisms with rejection and transplant nephropathy.~Details~Individuals with a renal transplant in whom a renal biopsy is indicated because of clinical reasons will be informed about aims and course of the study as well as potential risks and complications of the biopsy procedure. Then they will be asked to participate.~Should the patient decide for participation, he again will be made aware about potential risks and complications of the biopsy procedure using the official information sheet of the hospital on biopsy procedures and a special information sheet affiliated to the study documents. After reading the information sheets, the patients will be asked to sign the agreement. With the patients´ approval, two specimens of the renal transplant will be obtained. The Patient will be monitored for 24 hours clinically and by blood pressure measurements, urinalysis as well as by ultrasound scanning.~If there are no complaints and the controls are alright, the patient may check out of the hospital but is asked to return for a control examination one week later. At this presentation a physician familiar with the study will examine the patient clinically and by ultrasound. The levels of electrolytes, BUN and serum-creatinine will be detected and a venous blood gas analysis will be performed. In case that regarding the consequences of the biopsy everything is fine, the study is finished for this patient. He will be asked to present again, if new symptoms will arise.~While one part of the specimens obtained for diagnostics will be prepared for the study of gene expression immediately after the biopsy procedure, the other will be transported to the institute of pathology and worked up as usual.

Previous studies in animals revealed, that the activity of certain transporters along the nephron is changed with acute rejection after renal transplantation. We intend to investigate underlying mechanisms occurring in man in renal biopsy specimens obtained from patients because of acute rejection of the transplant or chronic transplant nephropathy.

The overall aim of CALERIE Phase 2 is to test the hypothesis that two years of sustained caloric restriction (CR), involving a reduction in energy intake to 75% of baseline (25% CR), in healthy, non-obese men aged 21-50 (inclusive) and women aged 21-47 (inclusive), will result in the same adaptive changes that were observed in a wide variety of animal studies. Particular emphasis is on the adaptive responses thought to be involved in slowing the aging process and protecting against age-related disease processes. Primary outcomes include core body temperature and resting metabolic rate. Secondary outcomes include risk factors for cardiovascular disease, inflammatory markers, immune function, psychological and physical function; oxidative changes in lipids, proteins, and DNA; and, risk factors for age-related conditions such as diabetes and body composition. An important secondary aim is to identify potential adverse effects of CR in humans.~The study will be conducted as a multi-center, parallel-group, randomized, controlled trial (RCT). A sample of 200 participants will be enrolled, and assigned to either the CR intervention or a control group. Control participants will be advised to simply continue their current diets. Participants in both treatment arms will be followed over a period of 24 months. A comprehensive set of evaluations will be performed prior to initiating the intervention, with follow-up evaluations at 1, 3, 6, 9, 12, 18 and 24 months afterwards.

The purpose of this study is to test the hypothesis that two years of sustained 25% caloric restriction (CR) in men age 21-50 (inclusive) and women age 21-47 (inclusive) will slow aging and protect against age-related disease processes.

Selenium is an essential nutrient. The Recommended Dietary Allowance (RDA) for selenium is considered to be the amount required to optimize plasma selenoproteins. There are two selenoproteins present in the plasma: selenoprotein P (Se-P) and glutathione peroxidase 3 (GPX-3). Although the amount of selenium required to optimize GPX-3 has been determined, the amount required to optimize Se-P in the plasma remains unknown. We aim to determine this amount by supplementing selenium deficient subjects with varying amounts of selenium as selenomethionine.~The study will take place in Mianning County, China, where selenium status is low. Approximately 150 people will be screened for eligibility to participate in this study. 98 subjects will be enrolled. Background information obtained from each participant will be: age, height, weight and smoking status.~Subjects will be randomized to a selenium supplement group. The selenium supplement will contain either 0, 20, 40, 60, 80, 100, or 120 µg of selenium as selenomethionine. A CDC worker will visit each participant daily to give them their selenium supplement. The CDC worker will watch them take their supplement and will ask if they have any unanticipated problems. Blood samples of 20 ml will be obtained at weeks 0, 4, 8, 12, 16, 20, 24, 32, and 40. Hair samples and 24-hr urine collections will be obtained at 0, 20 and 40 weeks. The total study duration is 40 weeks.

The purpose of this study is to determine the amount of selenium as selenomethionine that is required to optimize selenoprotein P in selenium-deficient Chinese subjects

HIV is a serious, life threatening illness that requires a lifetime of treatment and disease management. Studies have shown that it can be very difficult for infected mothers to decide whether and/or when to disclose their HIV serostatus to their uninfected children. HIV-infected parents struggle with the fear that their children will be forced to grow up too quickly, become worried or depressed, or be angry with their parents once they learn that their parents have HIV. Family-based intervention programs have been successful in helping facilitate the disclosure process. This study will develop and evaluate the effectiveness of an intervention designed to assist HIV-infected mothers of young children in determining whether and how to appropriately disclose their HIV serostatus to their children.~Participants in this study will be randomly assigned to either the intervention or a standard of care condition. The intervention will consist of three 75-minute sessions that will focus on exploring mothers' concerns, determining children's readiness to receive the news, planning for disclosure, and practicing disclosure. Participants will also receive one follow-up phone call from the therapist about 3 weeks after the last session. Sessions will be scheduled at times that are convenient for the participants and therapists. Follow-up visits will include both mothers and their children, and will be held at Months 3, 6, and 9 following the end of the intervention. Assessments will include readiness to disclose HIV serostatus, mental health indicators, and family functioning.

This study will develop and evaluate the effectiveness of an intervention designed to assist HIV-infected mothers of young children in determining whether and how to appropriately disclose their HIV serostatus to their children.

Objectives:~To determine the prevalence of nonadherence in our population~To assess possible causes of nonadherence and correlate those causes with demographic information and clinical findings~To assess for differences between adherence with immunosuppressive regime versus adherence with other medications (for hypertension, diabetes, hypercholesterolemia)~Methods:~A standardized interviewer-administered confidential survey exploring levels of adherence to transplant medications and other medications as well questionnaires on a variety of cognitive and other factors known to be associated with adherence~A brief review of demographics and pertinent laboratory information at the same encounter

Goal:~To define the causes and issues associated with nonadherence in our population~Hypothesis:~There is a difference in the rates and patterns of adherence to transplant medications versus other medications also taken by transplant patients~Methods:~A standardized interviewer-administered confidential survey exploring levels of adherence to transplant medications and other medications as well questionnaires on a variety of cognitive and other factors known to be associated with adherence.~A brief review of demographics and pertinent laboratory information at the same encounter

This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to determine the effect of a single 30 mg/kg IM dose of motavizumab on viral load in the upper respiratory tract of children who present with RSV illness but who do not require hospitalization. Participants were randomly assigned in a 1:1 ratio to 30 mg/kg motavizumab or placebo as soon as possible after a child's diagnosis of RSV and his/her eligibility for the study had been confirmed. Randomization was stratified by age (<6 months and greater than or equal to 6 to less than or equal to 12 months of age) and by site. Enrollment of an initial 100 children (50 per treatment group) will take place at multiple sites beginning in the 2006-2007 RSV season. The study was terminated early due to inability to enroll the planned number of participants.

This was a Phase 2, randomized, double-blind, placebo-controlled, multicenter study to determine the effect of a single 30 mg/kg intramuscular (IM) dose of motavizumab on viral load and motavizumab levels in the upper respiratory tract of children who present with RSV illness but who do not require hospitalization. Using 1:1 randomization, 30 mg/kg motavizumab or placebo will be administered as soon as possible after a child's diagnosis of RSV and his/her eligibility for the study has been confirmed.

The purpose of this study is to examine in stimulated cycles a) whether there is a difference in expression of steroid receptors in stroma and glands of endometrium between different days during the follicular phase b)whether there are secretory changes detected by endometrium histology before ovulation c)whether there is an association between expression of steroid receptors in endometrium and exposure to oestradiol and progesterone during the follicular phase.

Expression of steroid receptors in endometrium during ovarian stimulation.

We hypothesize that smoking cessation counseling improves with the implementation of a smoking status assessment data sheet in routine consults. This is a quality improvement study design to evaluate the impact of the implementation of a more formal smoking status evaluation in a resident/faculty driven outpatient clinic. This will be an observational study in which differences in quality measures will be compared between baseline and re-measurement periods. Population target: 900 patients screened before and after the implementation of the QI intervention. Primary outcome: smoking status evaluation. Secondary Outcome: number of patients advised to quit, plan implementation for smoking cessation, smoking cessation program referrals, number of NRT and bupropion prescription.

The researchers hypothesize that smoking cessation counseling improves with the implementation of a smoking status assessment data sheet in routine consults. This is a quality improvement study design to evaluate the impact of the implementation of a more formal smoking status evaluation in a resident/faculty driven outpatient clinic.

This study aims to reduce the duration of VRE intestinal carriage by the administration of Lactobacillus casei rhamnosus (strain Lcr 35 LC). Patients will be blindly randomized to be assigned to a 5 weeks regimen with the probiotic (10 9 lactobacillus bid) or to a 5 weeks regimen with placebo.A stool culture will be performed every week for 5 weeks (during the administration of treatment) then every two weeks until 3 consecutive negative stool culture for VRE.

This study aims to reduce the duration of VRE intestinal carriage by the administration of Lactobacillus casei rhamnosus (strain Lcr 35 LC). Patients will be blindly randomized to be assigned to a 5 weeks regimen with the probiotic (10 9 lactobacillus bid) or to a 5 weeks regimen with placebo.A stool culture will be performed every week for 5 weeks (during the administration of treatment) then every two weeks until 3 consecutive negative stool culture for VRE.

Recent studies have shown the encouraging effects of fitness training on human cognition, and brain structure and function. Such effects are of great interest both for what may they tell us about the nature of cognitive and brain aging and also for their public health implications. This study will test the hypotheses that: 1) improvements in aerobic fitness of older adults will lead to improved performance on a variety of cognitive processes, and especially those processes that are supported by frontal regions of the brain; 2) improvements in cognitive processes due to enhanced aerobic fitness will be visible on fMRI scans, and will be similar to those of young adults; 3) improvements in aerobic fitness, over the course of a 1 year intervention, will result in increases in gray and white matter volume.~One hundred forty sedentary older adults will be recruited for this study. Participants will be randomized to an aerobic exercise intervention group, or to a stretching and toning control group. Aerobic exercise sessions will be conducted three times a week for one year, beginning at a light to moderate intensity level over the first two months and progressing to a moderate to high level for the remainder of the year. The control group will meet on the same basis as the intervention group, and will participate in an organized program of stretching, limbering, and toning for the whole body that is specially designed for individuals 60 years of age and older.~During this time, participants will exercise, keep a daily exercise log detailing distance walked (routes will be measured and mapped for participants), time spent in aerobic activity, degree of intensity (rating of perceived exertion), general level of affect during exercise, resting and exercise heart rates. Participants will participate in the MRI/fMRI, physiological (cardiorespiratory) and psychosocial testing prior to the beginning of the fitness training intervention, following 6 months of fitness training, and at the conclusion of the 1 year of fitness training.

The purpose of this study is to examine the effect of aerobic fitness training on human cognition, brain structure, and brain function of older adults.

There are no FDA approved medications in the U.S. to augment lactation. Metoclopramide is used off-label but can have intolerable side effects. We examined the biological activity and safety of recombinant human prolactin (r-hPRL) as preliminary data for its use to augment lactation. Healthy, non-postpartum women (n=21) with regular menstrual cycles underwent a 7 day randomized, double-blind, placebo-controlled trial of r-hPRL. Galactorrhea, markers of bone turnover, calcium homeostasis and gonadal function were measured and side effects recorded.

Medications used to increase breast milk production increase prolactin secretion, the main hormone of lactation. There are no FDA approved medications used to improve breast feeding, but metoclopramide is used off-label and can have intolerable side effects. We examined the biological activity and safety of recombinant human prolactin (r-hPRL) as a potential medication to augment lactation. In this study, the effect of r-hPRL on breast milk production in women who did not recently deliver a baby and its effect on the bones and menstrual cycle were tested.

This project supports the post-third-grade assessment of 693 children and their families who were enrolled in a randomized trial of a program of prenatal and infancy home visitation by nurses that was epidemiologically and theoretically grounded. The sample enrolled was composed of low-income women who had no previous live births and who were largely African American (92%), unmarried (98%), and adolescent (67%) at the time of registration during pregnancy. In earlier phases of assessment, the program was found to improve the quality of care patients provided to their children, to reduce children's health-care encounters in which injuries were detected, to increase children's sequential processing skills as measured by the KABC, to reduce the number of dysregulated aggressive and violent themes expressed in their response to the MacArthur Story Stem Battery, and so to improve maternal life-course as reflected in fewer subsequent pregnancies, reduced use of welfare, and increases in the marriage and cohabitation with the biological father of the child. Many of the benefits in the area of parental care-giving and child functioning were concentrated in those children and their mothers who had few psychological resources (where psychological resources was defined as the absence of mental disorder symptoms, adequate intellectual functioning, and belief in their control over their life circumstances).~The project will determine whether the beneficial effects of the program on maternal, child, and family functioning extend through the early elementary school years, giving particular attention to maternal life-course and children's emerging antisocial behavior. Assessments of the children will be based on both mother and teacher reports. Teachers are independent, natural raters of the children's adaptation to an important social context. There are numerous reasons to expect that, from a developmental perspective, the effects of the program will increase as children experience the increased academic demands associated with entry into third grade. In addressing these questions, the current study will determine the extent to which this program of prenatal and infancy home visitation by nurses can produce enduring effects on maternal and child functioning (giving particular attention to the prevention of early-onset disruptive behavior disorders) in urban African Americans that are consistent with those achieved with whites in a central New York state county in a separate trial of this program conducted over the past 20 years.

This project supports the post-third-grade assessment of 693 children and their families who were enrolled in a randomized trial of a program of prenatal and infancy home visitation by nurses that was epidemiologically and theoretically grounded. The project will determine whether the beneficial effects of the program on maternal, child, and family functioning extend through the early elementary school years, giving particular attention to maternal life-course and children's emerging antisocial behavior. Assessments of the children will be based on both mother and teacher reports. Teachers are independent, natural raters of the children's adaptation to an important social context. There are numerous reasons to expect that, from a developmental perspective, the effects of the program will increase as children experience the increased academic demands associated with entry into third grade. In addressing these questions, the current study will determine the extent to which this program of prenatal and infancy home visitation by nurses can produce enduring effects on maternal and child functioning (giving particular attention to the prevention of early-onset disruptive behavior disorders) in urban African Americans that are consistent with those achieved with whites in a central New York state county in a separate trial of this program conducted over the past 20 years.

This project supports a 9-year follow-up of 650 children and their families who were enrolled in a randomized trial of prenatal and infancy home visiting by paraprofessionals and by nurses; participating families were assigned to control, paraprofessional-, or nurse-visited conditions. Earlier phases of assessment found significant benefits for nurse- and paraprofessional-visited families and children, although the nurse effects tended to be larger. The current phase of follow-up is designed to determine whether the effects of the nurse and paraprofessional programs endure and grow through the child age 9.5.~The project is organized around seven questions:~Do the programs of nurse and paraprofessional home-visiting produce enduring effects on: a) mothers' life-course; b) qualities of care parents provide to their children; c) children's early-onset behavior problems; d) children's incoherence and aggression/destruction in response to story stems; e) children's executive, language, and intellectual functioning and school achievement?~To what extent are the beneficial effects of the programs on parental care-giving and children's development concentrated on those born to mothers with few psychological resources?~To what extent are the benefits of the programs on mothers and children equivalent for Mexican- Americans and European-Americans?~To what extent are the effects of the programs on antisocial behavior concentrated on boys? 5. To what extent are program effects moderated by school and neighborhood contexts?~6. To what extent are the effects of the programs on children's development explained by impacts of the programs on women's prenatal smoking, maternal life-course, qualities of parental caregiving, and children's earlier language development, executive functioning, and emotional regulation? 7. To what extent are the initial costs of the programs recovered in reduced expenditures for other government services during the first nine years of the first child's life?

To examine the impact of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through 9.

Of all people diagnosed with cancer, 25% will have their cancer come back and spread to the bones. This often results in significant pain and suffering. Radiation treatment is often recommended as a safe and quick treatment that gives most people good relief from bone pain within a couple of weeks. However, some people can experience a short episode of increased pain called a flare a day or two after radiation treatment that lasts about a day. Studies suggest that around a third of all people who receive radiation treatment to help pain from cancer in the bones will have a pain flare. This study is being done because it would be helpful to prevent extra bone pain from happening to people after they receive radiation treatments. The purpose of this study is to find out if a medication called dexamethasone can help prevent pain flare as a result of radiation therapy.

Radiation treatment is often recommended as a safe and quick treatment that gives most people good relief from bone pain within a couple of weeks. However, some people can experience a short episode of increased pain (called a 'flare') a day or two after radiation treatment, that lasts about a day. The purpose of this sturdy is to find out if a medication called dexamethasone can help prevent pain flare as a result of radiation therapy.

The national recommendations of sedation concerning the intubation in emergency settings advise the use of a hypnotic, etomidate associated to succinylcholine. A national inquiry showed that more than 80% of prehospital intubations use a rapid sequence intubation as sedation. However, several recent studies throw into question the use of etomidate in this indication. Indeed, etomidate is a powerful inhibitor of the synthesis of cortisol. Adrenocortical hormone insufficiency is clearly associated to an increase in the morbidity-mortality of critically ill patients. Several authors advise therefore against the use of etomidate for such patients. Yet, to date, only indirect arguments associating the use of etomidate with excessive morbidity-mortality exist. A real causality link is not yet established. Another hypnotic that could constitute a therapeutic alternative to the use of etomidate exists: ketamine. The advantage of this molecule is that it does not inhibit the adrenocortical hormone axis.~Objectives: To evaluate sedation using ketamine versus etomidate in term of morbidity-mortality in critically ill patients intubated in the prehospital setting.~Experimental diagram: A prospective, multicentric, randomized, controlled, simple blind trial with independent analysis of the primary outcome.~The expected benefit is a reduction of the morbidity of patients admitted in the intensive care unit having received ketamine for intubation. The risks incurred for patients being suitable to this research are bound essentially to the adverse effects of ketamine. These include some psycho-dyslectic manifestations: nightmare, unpleasant awakening, and disruption of the visual, auditory sensations and mood, a sensation to float and sometimes depersonalization. These adverse effects are warned by a continuous administration of benzodiazepines.

The expected benefit is a reduction of the morbidity of patients admitted in the intensive care unit having received ketamine for intubation.

Postoperative pain is still a significant problem for surgical patients. Conventional use of narcotics for postoperative pain relief is not without serious side effects such as respiratory depression and sedation.There are other alternatives for postoperative analgesia as NSAIDs especially COX2-inhibitors. For some specific operation such as TURP which Foley's catheter needed to be retained for a few days,urinary anti spasmodics may help the patients to be more comfortable.~Comparison(s): There is a difference in postoperative morphine consumption in the first 24 hours after transurethral prostatectomy between patients who received etoricoxib or flavoxate or both and placebo.

The purpose of this study is to determine whether etoricoxib, flavoxate, both are effective in the treatment postoperative pain after TURP.~The research hypothesis:~There is a difference in postoperative morphine consumption in the first 24 hours after transurethral prostatectomy between patients who received etoricoxib or flavoxate or both and placebo.

To compare the Octopus 311 and the HFA 700 series to evaluate reliability, reproducibility, test duration, patient preference and technician preference.

To compare the Octopus 311 and the HFA 700 series

Primary: To compare the gastroprotective effects of a once-daily dose of PA 325 combination tablet combining 325 mg pH sensitive aspirin and 20 mg immediate release omeprazole versus a once-daily dose of 81 mg enteric coated (EC) aspirin utilizing Lanza scores from endoscopy findings in normal healthy volunteers.~Secondary: To evaluate the safety and gastrointestinal tolerability, including ulcerogenic potential, and the effect on gastric pH of PA 325.

To compare the gastroprotective effects of a once-daily dose of PA 325 combination tablet

This is a Phase 1, dose escalation study of EC0225 administered by intravenous bolus (IV) during weeks 1 and 3 of a 4-week cycle to patients with refractory or metastatic cancer who have exhausted standard therapeutic options. EC0225 is a drug that is specifically designed to enter cells via a folate vitamin receptor. Experimental evidence shows that the target receptor is over-expressed in many human cancers. There are no previous human studies of EC0225; however, lab research (research in test tubes or animals) using EC0225 has shown activity against tumors in animals. This activity in animal models suggests that EC0225 may be useful as chemotherapy against human cancers. The primary objective of this study is to determine the safety and maximum tolerated dose of EC0225 given by intravenous bolus. The efficacy of treatment will also be measured.

This is a Phase 1 clinical trial evaluating the safety and tolerability of escalating doses of EC0225 in patients with refractory or metastatic tumors who have exhausted standard therapeutic options.

PA 325 is proposed for the reduction in the risk of aspirin-associated gastrointestinal (GI) adverse events in patients requiring daily aspirin. This study is designed as a Proof of Concept study to evaluate the gastroprotective effects, pharmacokinetic profile, and safety of PA 325 in healthy volunteers.~To compare the gastroprotective effects of a once-daily dose of PA 325 combination tablet combining 325 mg pH-sensitive aspirin and 20 mg immediate release omeprazole versus a once-daily dose of 325 mg enteric coated aspirin utilizing Lanza scores from endoscopy findings in normal healthy volunteers.

Primary: To compare the gastroprotective effects of a once-daily dose of PA 325 combination tablet combining 325 mg pH sensitive aspirin and 20 mg immediate release omeprazole versus a once-daily dose of 325 mg enteric coated aspirin utilizing Lanza scores from endoscopy findings in normal healthy volunteers.

In the United States, labor inductions have increased from 11% of all pregnancies in 1989 to 21% in 2004. Although the indications for labor induction vary, labor inductions as an obstetrical practice are associated with an increased risk of Cesarean delivery. As such, the rise in labor inductions has been paralleled by a rise in the cesarean rate to an all time high of 30%. The risk of cesarean can be mitigated with the use of cervical ripening agents in the setting of an unfavorable cervix. Both pharmacological ripening agents and mechanical methods are currently available for cervical priming. Methods available for mechanical dilation include, but are not limited to transcervical foley catheter alone and transcervical foley catheter with an extra-amniotic saline infusion or EASI. The potential advantage of EASI to transcervical foley catheter alone is the promotion of endogenous prostaglandin release by membrane stripping and supplying additional mechanical force. It may be disadvantageous by increasing the risk of chorioamnionitis or by diluting the prostaglandins that are released by membrane stripping. There have been two randomized trials comparing foley alone to foley with EASI. Because the results of these two trials are conflicting, we chose to conduct a randomized clinical trial of foley catheter compared to foley catheter with an EASI for labor induction and cervical ripening in women with an unfavorable cervix.

The purpose of this study is to compare the efficacy of a transcervical Foley catheter with and without extra-amniotic saline infusion (EASI) for priming the cervix for labor.

Nearly half a million children are born each year to single, low-income mothers. Children born to socially disadvantaged mothers are more likely to experience chronic health problems, encounter child abuse and neglect, and receive insufficient health care. Home visitation by nurses during pregnancy and early childhood may prevent a wide range of health and developmental problems in children born to women who are either teenagers, unmarried, or of low economic status.~This study is associated with a home nurse visitation program that first began with 400 socially disadvantaged pregnant women between the years of 1977 and 1980 in an upstate New York semi-rural county. Participants in the original study were randomly assigned to participate in the home nurse visitation program or receive comparison services from pregnancy until the child's second birthday. Participants assigned to receive comparison services were provided with free transportation for prenatal and child care, as well as sensory and developmental screening for the child. Participants assigned to the home nurse visitation program were visited at home by a nurse 9 times during pregnancy and 23 times during the child's first 2 years of life. A follow-up study concluded that the home nurse visitation program reduced the number subsequent pregnancies, use of welfare, child abuse and neglect, and criminal behavior on the part of the socially disadvantaged mothers for up to 15 years after the birth of their first child.~This follow-up study will determine whether a home nurse visitation program has continued long-term effects on a child's health and development, 27 years later. Specifically, this study will evaluate whether the nurse-visited young adult offspring differ from the comparison group in their economic productivity; rates of child abuse and neglect; criminal behavior; mental health; abuse of substances; use of welfare, foster care, and healthcare in relation to government expenditures; and quality of their partnered relationships. Participants within the nurse-visited program group will be compared with each other to determine whether certain characteristics or factors, such as genetic vulnerabilities, environmental risks, or a history of child abuse, make someone less likely to benefit from a home nurse visitation program.

This study will evaluate the long-term effects of a prenatal and early childhood home nurse visitation program for socially disadvantaged women and their children.

Prior studies have demonstrated significant variability in platelet response to clopidogrel in patients with coronary artery disease (CAD). Up to 25% of patients have been shown to be non-responders to a conventional dose of clopidogrel. This phenomenon has been associated with higher incidence of recurrent cardiovascular (CVS) adverse events in patients with acute coronary syndrome (ACS), and higher incidence of peri-procedural myocardial damage, thrombotic complications, and ischemic events in patients undergoing elective percutaneous coronary intervention (PCI). Both the ex-vivo anti-platelet effect and the clinical benefit of clopidogrel are dose related. Moreover, in patients sustaining ACS while on maintenance clopidogrel treatment, reloading with 600 mg clopidogrel, resulted in further reduction in platelet aggregation, although the patients were not non-responders. Despite this, the effect of dose escalation has never been examined in patients resistant to clopidogrel. In the present study we wish to assess prospectively the effect of reloading with 600 mg clopidogrel, and double dose maintenance treatment (150 mg/day) for one month in acute myocardial infarction (AMI) patients who demonstrate non-respondese to clopidogrel.

Laboratory clopidogrel resistance is associated with adverse atherothrombotic events in patients with coronary artery disease. In the proposed study we wish to prospectively assess the effect of reloading with 600 mg clopidogrel, and administer maintenance treatment with clopidogrel 150 mg/day for one month in a group of acute myocardial infarction (AMI) patients who demonstrate non-responsiveness to clopidogrel.

Context. Increased blood glucose levels frequently occur in critically ill patients and its normalization by intensive insulin treatment markedly improves clinical outcome.~Objective and Design: Randomized controlled trial to compare blood glucose control by the model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RMP) in peri- and postoperative period in cardiac surgery patients.~Setting: Department of Cardiac Surgery, University Hospital. Patients. 60 cardiac surgery patients. Interventions. Elective cardiac surgery and treatment with continuous insulin infusion to maintain euglycemia (target range 4.4 - 6.1 mmol/l). 30 patients were randomized for eMPC and 30 for RMP treatment. Blood glucose was measured in 1-4 hour intervals depending on request of each algorithm during surgery and post-operation period for 24 hours.~Main Outcome Measures. Mean blood glucose, percentage of time in target range. Results. Mean blood glucose was 6.15 ± 1.11 mmol/l in eMPC vs. 7.21 ± 1.08 mmol/l in RMP group (p<0.05); percentage of time in target range was 60.4 ± 22.8% for eMPC vs. 27.5 ± 16.2% for RMP group (p<0.05). No severe hypoglycemia (blood glucose bellow 2.9 mmol/l) was observed during the study. Average insulin infusion rate was 4.67 ± 3.34 in eMPC vs. 2.57 ± 1.66 IU/h in RMP (p<0.05), average sampling interval was 1.46 ± 0.31 vs. 2.10 ± 0.22 hours (p<0.05).~Conclusions. eMPC algorithm was more effective and comparably safe as compared to RMP in maintaining euglycemia in cardiac surgery patients.

Randomized controlled trial to compare blood glucose control by the model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RMP) in peri- and postoperative period in cardiac surgery patients.

Spinal fusion can be associated with significant blood loss requiring allogeneic blood transfusion (ABT). Ongoing concerns about the costs, risks, and availability of allogeneic blood have prompted the implementation of multiple techniques (preoperative erythropoetin, autologous pre-donation, intra-operative blood salvage, and induced hypotension) to reduce the necessity of ABT. However, 28% of patients undergoing spinal fusion at the Toronto Western Hospital still receive ABT. Also, none of these modalities (with the exception of induced hypotension) actually reduce the amount of blood shed from the surgical wound; thus the severity of anemia is largely unaffected. Consequently, many of these patients can suffer from adverse effects of anemia postoperatively as well as potential complications from blood transfusions.~The underlying assumption of the proposed study is that excessive fibrinolysis occurs during spinal fusion surgery. This can result in increased and recurrent blood loss, which can exacerbate the significant amount of bleeding already associated with major spine surgery.~Tranexamic acid - an antifibrinolytic drug blocks the dissolution of hemostatic fibrin, which stabilizes fibrin structures, and thus may decrease blood loss secondary to increased fibrinolysis.~This research proposal will test the following hypotheses:~Tranexamic acid reduces the estimated perioperative blood loss in adult patients undergoing elective spinal fusion.~Tranexamic acid reduces the need for blood transfusion in adult patients undergoing elective spinal fusion.~This multi-centered trial will be valuable for establishing the efficacy and safety of tranexamic acid for reducing blood loss and allogeneic blood transfusion in adults having elective spinal fusion. Tranexamic acid is easy to administer, is relatively inexpensive, and has not been associated with significant adverse effects. If it is shown to be efficacious, it can be incorporated into routine clinical practice as part of the multi-modal perioperative blood conservation techniques currently used to reduce perioperative blood loss, transfusion and the risk of allogeneic blood transfusion.

Spinal fusion surgery can be associated with significant blood loss requiring allogeneic blood transfusion. Tranexamic acid is a synthetic amino acid with antifibrinolytic action that has been shown to reduce perioperative blood loss in patients undergoing cardiopulmonary bypass for cardiac bypass surgery, knee replacement and liver transplantation surgeries. The efficacy of antifibrinolytics for reduction of blood loss in major spine surgery has not been well studied in adult patients. The objective of this study is to determine the efficacy of tranexamic acid in reducing perioperative blood loss and blood transfusion in adults undergoing elective spinal fusion in a larger, multi-centered, randomized, double-blinded, placebo controlled trial.

Patients commonly report that they have been dreaming when they emerge from anaesthesia. Data from observational studies and small randomised trials suggests that reports of dreaming are more commonly made after anaesthesia maintained with propofol than anaesthesia maintained with inhaled anaesthetic agents. We propose to randomise 300 healthy patients to receive a standardised general anaesthetic for surgery that includes either propofol or desflurane for maintenance. We will measure the raw and processed electroencephalogram during and after anaesthesia and interview patients about dreaming as soon as they emerge from anaesthesia.

We hypothesise that patients who receive propofol for maintenance of anaesthesia will report dreaming more often when they emerge from anaesthesia than patients who receive desflurane for maintenance of anaesthesia.

Assessment of Families Who Have Undergone the Traumatic Loss of a Child Study Protocol~The present study will focus on several objectives in the framework of the family perspective and systemic understanding of the mourning process:~Identification of the psychological, social and practical needs of families that have lost a child to terrorism.~Deepening and extending the knowledge of how families cope with the loss of a child in a violent incident of a security-related nature.~Identification of risk and resilience factors within the family structure, and the nature of the relationships within the family.~The University of Al-Quds in East Jerusalem will be conducting an identical study in conjunction with this one, examining Palestinian families who have lost a child in the conflict with Israel. Collaboration between these studies will allow a cross-cultural comparison of family coping with traumatic loss, and of the identification of resilience and risk factors among the families.~Method of the study Participants. The assessment process will include some twenty-five Israeli families who have lost a son or daughter below the age of 18 as a result of a terrorist incident, at least six months previously. All family members living at home will participate in the study. The study will not include single-parent families, or family members who suffer from mental retardation, disturbances because of addiction, or psychiatric disturbance from the psychotic or autistic spectra (schizophrenia, manic-depressive illness, psychotic disturbances, PDD).~Procedure. The recruitment of families will be done by the Kobi Mandel Foundation, which is involved in helping families that have been victims of terror. The Foundation will not approach families who fit the criteria of ineligibility for the study, as described in the previous paragraph. The parents will fill out a form of informed consent on their own behalf, and on behalf of their children who are under the age of 18, after they have received an explanation about the procedure of the study, and have been given an opportunity to ask questions about it. Teenagers over 14 years old will sign a form of informed consent, with parental permission. Family members over the age of 18, living at home, will fill out a form of informed consent on their own behalf.~To carry out this stage, each family will be assigned a professional by the Israel Center for the Treatment of Psychotrauma, who will be its liaison and responsible for the process of assessment. The completion of the questionnaires will be coordinated with the family members, and carried out in the presence of the liaison, who will assist in explaining the questionnaire, and provide support in the event of emotional difficulties arising.~Every member of the family will fill out the questionnaire separately; the liaison will focus on helping children who have difficulty doing so. The parents will fill out questionnaires for small children (under 10 years old). In order to preserve the privacy of the participants, each family member will receive a personal code to be written on the questionnaire. The liaison alone will have the key to identify each participant, which is important for the identification of needs within the family, and the ability to direct them for appropriate treatment.~Possible risks. The main risk for the participants relates to the possible uncomfortable feeling the questionnaire might raise by evoking memories of the deceased, and to personal distress. For this reason, the questionnaires will be given to the participants by a trained professional who will be able to provide support, identify distress and suggest seeking professional treatment if necessary.~Qualifications of the Principal Investigators. The work will be carried out under the supervision of Dr. Danny Brom, the founder and current director of the Israel Center for the Treatment of Psychotrauma.~Description of the research instruments Demographic and organizational details. The participants will relate to demographic details like age, sex, family status, place in the family, occupation and socio-economic status, as well as information about the death (circumstances and time of death, description of the loss).~McMaster Family Assessment Device (FAD): This questionnaire contains 60 self-reported items that assess six aspects of family functioning: Problem solving, Communication, Roles, Affective responsiveness, Affective involvement, Behavior control In addition, the questionnaire contains a component (12 items) of general functioning (Epstein, Baldwin and Bishop, 1983).~Couple adjustment: Dyadic Adjustment Scale (DAS) (Spanier, 1976). The quality of mutual adjustment in the marital system will be measured by the DAS questionnaire, which contains 32 items in four subscales: Dyadic Consensus, Dyadic Satisfaction, Dyadic Cohesiveness and Affectional Expression.~Adults Grief Response: Inventory of Complicated Grief - ICG (Prigerson and Jacobs, 2001). The questionnaire examines adjustment to grief. Its 33 items measure non-adaptive symptoms of response to loss. The items make up two primary distress scales - traumatic distress and separation distress - which represent a uni-dimensional construct. The participants are asked to grade the degree to which they experience each of the symptoms presented, on a Likert scale of 1 (never) to 5 (always).~Exposure to trauma and post-traumatic distress. The PDS questionnaire (Foa, Feske & Murdock, 1993) will examine the history of traumatic events, subjective trauma response, post-traumatic symptoms and functional impairment. The questionnaire includes yes/no questions for the parent to answer regarding possible traumas in his or her past. Four yes/no questions examine the subjective response to the event (criterion A2). The section that examines post-traumatic symptoms includes 17 items that relate to the appearance of different symptoms, according to DSM, within the last month: re-experiencing the event (criterion B), avoidance (C) and hyperarousal (D). The scale of responses runs from 0 (not relevant or happened only once) to 3 (almost all the time). A grade of 2 or more is regarded as verifying the existence of a symptom.~Beyond this, the questionnaire contains nine yes/no questions that relate to impaired functioning in different areas of life, like work, relations with family members, leisure time activity, and so on.~Depression: Beck Depression Inventory (BDI-II). This widely accepted questionnaire measures the severity of symptoms of depression. It was updated in 1996 in order to meet the criteria of the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition). The participants are asked to relate to 21 items that describe different depressive symptoms on a scale of 0-3. A general score on the questionnaire can therefore lie between 0 and 63 (a higher score indicates greater severity of depressive symptoms).~Adolescents Grief response: UCLA Trauma Psychiatry Service Grief Inventory (Layne et al, 1998). On this questionnaire, the participants are required to answer ten items that relate to loss response, from 0 (not at all) to 4 (very much) on a Likert scale.~Post-traumatic symptoms. UCLA PTSD Reaction Index Adolescent Version (RI-R) (Rodriguez, Steinberg, & Pynoos, 1999). The RI-R is a new version of the earlier UCLA Reaction Index (Frederick, Pynoos, & Nader,1992), which was based on the DSM-III. The RI-R includes 22 items for self-report. It measures the frequency of post-traumatic symptoms in the previous four weeks. Subject are asked to note the frequency of symptoms on a scale from 0 (never) to 4 (most of the time). The measure of the severity of post-traumatic symptoms will be computed by summarizing 20 items on the questionnaire, as per Rodriguez et al (1999).~Functional impairment. This will be measured by means of items on the Diagnostic Predictive Scale (DPS), which relates to significant impairment in different areas of functioning (APA, 2000), for example: functioning in school, social relations, family relations, activity outside school and dangerous behavior. The participants will be asked to grade, on a scale of 0 (not at all) to 5 (very much) the degree to which they have experienced impairment in functioning in these areas. The severity of functioning impairment will be computed as the sum of all the items.~Exposure to traumatic events. This self-report questionnaire is a translation of the questionnaire by Ford et al. (1997), and works on the same basis. The subjects will be asked to answer, yes or no, whether they were ever exposed to one or more of 17 different traumatic events .~Strengths and difficulties. The Strength and Difficulties Questionnaire (SDQ), self-reported or filled out by parents, contains 25 items which assess different aspects of adjustment among children and adolescents focusing on behavioral symptoms. The questionnaire is intended to be completed by parents (or teachers) for children aged 3-16. Adolescents aged 11-16 can fill out the questionnaire by themselves (Goodman, 1997). The participants are asked to relate to 25 positive and negative statements, and respond as to what degree each statement fits their children, on a Likert scale of 1 (not true) to 3 (certainly true). The questionnaire is made up of five main factors: emotional symptoms, behavioral problems, attentiveness and hyperactivity, relations with the peer group, and pro-social behavior.~Children (Grades 3-6) Depression. Children Depression Inventory (CDI) (Kovacz, 1992) is a self-report questionnaire that assesses cognitive, affective, somatic and behavioral aspects of depression in children and adolescents from age 6 to 17. The original version of the questionnaire has 27 items, each containing three sentences. The child needs to choose the sentence that best describes his feelings over the previous two weeks. The scoring of the questionnaire presents a general score and five sub-scores: negative mood, interpersonal problems, ineffectiveness, anhedonia and self-image.~Anxiety. The Screen for Child Anxiety Related Emotional Disorders (SCARED), (Birmaher et al, 1997) is a self-report questionnaire that assesses anxiety symptoms in children. A general anxiety measure (eight items) and a separation anxiety measure (seven items) will be computed from the questionnaire. The subjects will be asked to grade, on a scale from 0 (generally not true) to 2 (generally true), the degree to which the items describes their situation. The general score on the two scales will be computed as the sum of the items.~Small children The report on the distress of small children in the family will be divided into two. For children aged 2-11, the parents will answer SDQs. For children aged 2-5, the parents will answer the Post-traumatic Stress Questionnaire. Each parent will answer a separate questionnaire.~Post-traumatic stress. The questionnaire is based on a semi-structured interview with the parents with respect to post-traumatic symptoms in their little children (ages 2-5) (Scheeringa & Zeanah, 1994). The parents will be asked to mark, on a scale of 0 (never) to 3 (yes), whether each one of the symptoms were evident in their children within the previous month.

The present study will focus on several objectives in the framework of the family perspective and systemic understanding of the mourning process:~Identification of the psychological, social and practical needs of families that have lost a child to terrorism.~Deepening and extending the knowledge of how families cope with the loss of a child in a violent incident of a security-related nature.~Identification of risk and resilience factors within the family structure, and the nature of the relationships within the family.

Limb loss can result from a variety of etiologies including diabetes, trauma and cancer. Following limb loss, individuals are at elevated risk for activity limitations and participation restrictions with significant impact on health and quality of life. Intervention: Working with the Amputee Coalition of America we have developed, evaluated, and established the effectiveness of a self-management program (PALS) to improve health and outcomes following limb loss. Literature suggests that the access to, and effectiveness and utilization of, this class of interventions may be enhanced by the concerted use of early intervention, peer mentorship, motivational interviewing and provider training. Objectives: Our goal is to evaluate the effectiveness of an enhanced, early self-management intervention- PALS Plus. The specific aims are:1) evaluate the effectiveness of the PALS Plus intervention in improving outcomes for persons with limb loss; (2) evaluate the effectiveness of the PALS Plus intervention in maximizing utilization of self-management interventions for persons with limb loss. Study Design and Participants: The prospective clinical trial will use a two group, lagged-control design to evaluate the intervention at five health care facilities. A cohort of 200 patients will be enrolled prior to implementation of the intervention and will serve as the control group. Subsequently, a second cohort of 200 patients will be enrolled and receive the PALS Plus intervention and will serve as the intervention group. Assessment will be at baseline, treatment completion and six month follow-up. Outcomes: Primary outcome measures are: pain, depressed mood, and positive mood. Secondary outcome measures are: function, participation and bothersomeness of limitations. Improvements in primary and secondary outcomes will result through the impact on self efficacy, patient activation, catastrophizing and social support. The investigation will also provide unique and valuable information regarding patients' acceptance and use of peer visitation and self-management following limb loss. Relevance: By establishing the utility and effectiveness of the enhanced self-management intervention, there is the potential to improve the health, activity, participation and quality of life for individuals with disabilities. The intervention addresses the areas of activity and participation in such a way that it can be implemented in local health care facilities working in combination with a national consumer based organization - the Amputee Coalition of America.

Limb loss can result from a variety of etiologies including diabetes, trauma and cancer. Following limb loss, individuals are at elevated risk for activity limitations and participation restrictions with significant impact on health and quality of life. Intervention: Working with the Amputee Coalition of America we have developed, evaluated, and established the effectiveness of a self-management program (PALS) to improve health and outcomes following limb loss. Literature suggests that the access to, and effectiveness and utilization of, this class of interventions may be enhanced by the concerted use of early intervention, peer mentorship, motivational interviewing and provider training. Objectives: Our goal is to evaluate the effectiveness of an enhanced, early self-management intervention- PALS Plus. The specific aims are:1) evaluate the effectiveness of the PALS Plus intervention in improving outcomes for persons with limb loss; (2) evaluate the effectiveness of the PALS Plus intervention in maximizing utilization of self-management interventions for persons with limb loss. A cohort of 200 patients will be enrolled prior to implementation of the intervention and will serve as the control group. Subsequently, a second cohort of 200 patients will be enrolled and receive the PALS Plus intervention and will serve as the intervention group. Assessment will be at baseline, treatment completion and six month follow-up. Outcomes: Primary outcome measures are: pain, depressed mood, and positive mood. Secondary outcome measures are: function, participation and bothersomeness of limitations. The investigation will also provide unique and valuable information regarding patients' acceptance and use of peer visitation and self-management following limb loss. Relevance: By establishing the utility and effectiveness of the enhanced self-management intervention, there is the potential to improve the health, activity, participation and quality of life for individuals with disabilities. The intervention addresses the areas of activity and participation in such a way that it can be implemented in local health care facilities working in combination with a national consumer based organization - the Amputee Coalition of America.

Biliary duct stenoses are caused by intrinsic malignant disease of the common bile duct or by compression or infiltration of malignancies of the abdominal organs, i.e. pancreas, liver, stomach, duodenum, etc, or by iatrogenic reasons such as endoscopic biliary stone manipulations, biliary anastomoses or biliary duct reimplantation. In these diseases, a stent can be placed in the biliary duct canal to open it and relieve the obstruction. The Allium Biliary Stent is to be inserted into the biliary duct to allow free flow of biliary fluid from the liver to the duodenum by supporting the obstructed area of the biliary duct lumen, keep it open, and prevent its re-obstruction.

The purpose of this study is to evaluate the safety and efficacy of the Allium Biliary Stent in malignant obstructions of the common bile duct.

Experimental studies have revealed that tea catechin extracts induce preventive effects on oxidative stress, but there have been few clinical trials conducted to verify the effects. Also, there have been few clinical markers indicating oxidative damage, and therefore, more accurate and reliable markers have been expected. The study is designed for evaluating the effects of tea catechin extracts on the frequency changes of micronuclei in peripheral lymphocytes as the indicator of oxidative damage, compared with other oxidative stress markers in late middle aged healthy volunteers.

The purpose of this study is to clarify the effects of tea catechin extracts on the frequency changes of micronuclei in peripheral lymphocytes compared with other oxidative stress markers in late middle aged healthy volunteers

A pharmacokinetic study of insulin pump treatment using Insulin Aspart. The study consist of three different periods A, B and C where a constant the insulin infusion rate is given during the periods. Each period will last 12 hours and blood will be drawn to measure absorbed Insulin Aspart. During period A will a constant the infusion rate of insulin be given. In period B and C will there at the start of the constant infusion rate be given a bolus. The bolus in period C is calculated on the basis of the results in period B, therefore will all participants experience period C last where as period A and B is randomized cross-over. Period C is written in the protocol as optional and it is evaluated after period A and B if period C will be performed.~The hypothesis is that steady state of insulin will be obtained faster in period B and C than A.

A pharmacokinetic study of insulin pump treatment using Insulin Aspart. The study consist of three different periods A, B and C where a constant the insulin infusion rate is given during the periods. In period B and C will the infusion start with a bolus.~It will be investigated if a steady state of insulin will be obtained faster in period B and C then A.

Drug treatment in elderly is not yet optimal. 20 to 30% of admissions of elderly aged over 80 are related to drug problems, most of them being preventable. To decrease drug related hospitalizations need iatrogenic prevention, compliance improvement, and underuse decrease. A multifaceted intervention has been designed, included three dimensions : 1/ drug optimization 2/ patient and/or caregiver education and 3/ better coordination with home health professionals before discharge.~A randomized trial has been designed to determine if this complex intervention can significantly decrease the risk of unplanned readmissions in this very elderly population, compared with usual care.

A randomized trial has been designed to determine if this complex intervention can significantly decrease the risk of unplanned readmissions in this very elderly population, compared with usual care.

HZT-501 is a combination product including ibuprofen and the acid reducing agent famotidine. The study is designed to determine whether the combination product reduces the rate of ulcer development in subjects who require long-term daily use of ibuprofen.~Subjects will be assigned randomly, in approximately a 2:1 ratio, to treatment with either HZT-501 (ibuprofen 800 mg/famotidine 26.6 mg) or ibuprofen (800 mg) three times daily for a 24 week treatment period or until they develop either an endoscopically-diagnosed upper gastrointestinal ulcer and/or prohibitive toxicity. Subjects will visit the study center for Screening and at Weeks 4, 8, 16, and 24. Physical exams will be performed, and clinical laboratory measurements made, at selected times during the study. Endoscopic exams will be performed during Screening and at Weeks 8, 16, and 24. Subjects will be contacted four weeks following study completion.

The purpose of this study is to evaluate whether HZT-501 is effective in reducing the rate of development of ibuprofen-associated ulcers in patients who require long-term daily use of ibuprofen.

Venous thromboembolism (VTE) is a potentially fatal disease with an estimated incidence of 0.1%. One third of the VTE occur as pulmonal embolism with a mortality up to 25% (White RH. Circulation 107:2003)~Serum d-dimer levels are used as sensitive marker for the diagnosis of VTE (Kelly J et al. Arch Intern Med, 162: 2002). Because of its sensitivity, the determination of serum D-dimer levels is an accepted method to exclude VTE in the outpatient setting meaning that VTE may be excluded in case of normal D-dimer levels (Kelly J. Lancet 359: 2002). The specificity of the D-dimer testing, however, is low. This is true especially in the postoperative phase. The interpretation of elevated D-dimer levels in surgical patients remains elusive.~The natural kinetics of D-dimers after surgery is not known. The question to what extent D-dimer levels rise after surgery and how long it may take D-dimer levels to return to normal after surgery is not yet determined. This information is needed to be able to use D-dimer testing for VTE diagnosis in surgical patients.~In this study, D-dimer levels are measured in surgical patients immediately before (day 0) and repeatedly after surgery. D-dimer level measurement will be stopped after D-dimer levels returned to normal.

The purpose of this study is to investigate the natural kinetics of D-dimers that occur after abdominal surgery.

PURPOSE: To assess the impact of duration of topical steroid treatment on the incidence of endothelial graft rejection following normal-risk penetrating keratoplasty (PK). DESIGN: Prospective, institutional, longitudinal, randomized interventional trial including 406 eyes (age: 52 >= 19 years; follow-up: 42 >= 18 months). METHODS: Postoperative treatment started with prednisolone acetate 1% eye drops five times daily and was tapered over the first 6 months. Patients were then randomised into either short-term (stop topical steroid treatment) or long-term treatment (continue steroids once daily until 12 months). <=

PURPOSE: To assess the impact of duration of topical steroid treatment on the incidence of endothelial graft rejection following normal-risk penetrating keratoplasty (PK). DESIGN: Prospective, institutional, longitudinal, randomized interventional trial including 406 eyes (age: 52 >= 19 years; follow-up: 42 >= 18months). METHODS: Postoperative treatment started with prednisolone acetate 1% eye drops five times daily and was tapered over the first 6 months. Patients were then randomised into either short-term (stop topical steroid treatment) or long-term treatment (continue steroids once daily until 12 months).

Biomedical and biotechnology industry is internationally regarded as the most brilliant star performer of the future. The development of biomedical depends on a high quality academic research environment, while innovation and uniqueness should be emphasized for the development of biotechnology industry. The successful development of biotechnology industry will be impossible if the development is not based on extensive and in-depth research work and verification acquired from clinical implementation. Based on these concepts, the resources of research materials, especial of human being, are going to be essential. Thus, a programmable and systematic collection of clinical specimen would become one of the potential properties in hospital. This is a two-year pilot scheme, and was designed to start collecting specimen from Health Management Center in NTUH. This pilot scheme will address important issues of manpower, finances, and data merging for evaluation of biotechnological related specimen collection, such as cell or tissue bank, in the future.~There are 12471 persons who take the health examination in Health Management Center during 2004 Mar -2005 Dec. Subjects agree to be invovled in the study asre assigned as respondent. For those who disgree to be involved in the study are assigned as non-respondent. There are 6261 respondents and 6210 non-respondents in this study. 63% of respondents and 51% of non-respondents are males. There is a lower distribution in smoking, history of hypertension, and history of hyperlipidemia in respondents than in non-respondents. Respondents have lower level of triglyceride, HDL, LDL in blood than non-respondents do.

Biomedical and biotechnology industry is internationally regarded as the most brilliant star performer of the future. The development of biomedical depends on a high quality academic research environment, while innovation and uniqueness should be emphasized for the development of biotechnology industry. The successful development of biotechnology industry will be impossible if the development is not based on extensive and in-depth research work and verification acquired from clinical implementation. Based on these concepts, the resources of research materials, especial of human being, are going to be essential. Thus, a programmable and systematic collection of clinical specimen would become one of the potential properties in hospital. This is a two-year pilot scheme, and was designed to start collecting specimen from Health Management Center in NTUH. This pilot scheme will address important issues of manpower, finances, and data merging for evaluation of biotechnological related specimen collection, such as cell or tissue bank, in the future.

Recent research has revealed that children who are highly anxious prior to surgery experienced more problems post surgery. These problems included reporting of more pain and requested more pain medication during hospitalization and home follow up. Consumption of pain medication may not be the optimal pain management program. In contrast, numerous human-animal interaction studies have shown that animals tend to have a calming effect on people, reduce stress, and lesson anxiety. Therefore, the primary objective of this study is to examine the effect of pre surgery dog visits as compared to a costumed character or parents-only on the consumption of pain medication after surgery.

The objective of this study is to examine the effects of pre surgery dog visits as compared to a costumed character or parents-only on the consumption of pain medication after surgery. It is hypothesized that pre surgery dog visits will reduce post surgical stress and anxiety.

Objectives~Noninvasive stimulation of the central and peripheral nervous system, including transcranial magnetic stimulation (TMS), transcranial direct and alternating current stimulation (tDCS and tACS, respectively) and cutaneous/peripheral nerve stimulation (C/PNS) alone or paired with TMS (paired associative stimulation, PAS), has been increasingly used in the investigation of cortical plasticity and as a possible adjuvant strategy in neurorehabilitation. It has been shown that TMS, tDCS, tACS and C/PNS can modulate motor function in healthy volunteers, as well as in patients with neurological disorders such as stroke.~One fundamental problem is that the optimal parameters of stimulation to modulate motor function by all of these techniques are not known. The purpose of this protocol has been to explore within safe guidelines, the effects of different stimulation parameters on motor cortical function, on oscillatory brain dynamics measured with magnetoencephalography (MEG) and electroencephalography (EEG), on eye movements, and on fMRI activation. In addition, this protocol was used to train new fellows coming to NINDS Human Cortical Physiology Section (HCPS) in the use of TMS, tDCS, tACS and C/PNS techniques.~We expected that information emerging from these studies would allow us to 1) optimize experimental protocols or stimulation parameters to collect pilot data in healthy volunteers for future patient-oriented hypothesis-driven protocols, 2) to collect pilot data for power analysis for future patient-oriented hypothesis driven protocols, and 3) to train new fellows in the use of these different methods.~As instructed, we had stopped recruitment under this protocol at the time we were informed by the NIH IRB that they determined this to be a thematic protocol (August 6, 2019). The four specific aims addressed under this protocol are:~Aim 1. To identify resting behavioral and physiological substrates for neuromodulation of motor behavior~Aim 2. To identify task-dependent behavioral and physiological substrates for neuromodulation of motor behavior~Aim 3. To understand variability, rigor or/and reproducibility of brain stimulation effects.~As instructed, the purpose of this amendment is to request authorization to proceed with data analysis and publication. No new experiments will be carried out under this protocol.~Study Population~Up to 1500 healthy volunteers, age 18 and older.~Design~No new experiments will be carried out under this protocol. Previously, healthy volunteers received one or more of the following types of stimulation alone or in combination: (1) single- and paired-pulse TMS with inter-stimulus intervals of greater than 1s and up to 20s and intensities of up to 100% of stimulator output; (2) 1 Hz TMS for up to 30mins and up to 115% of resting motor threshold (RMT) intensity; (3) tDCS applied at an intensity of up to 4 mA for a duration of up to 60mins, as long the total charge does not exceed 7.2 C; (4) tACS applied at a peak-to-peak intensity of up to 4 mA for a duration of up to 60 minutes, as long the total charge does not exceed 7.2 C; (5) C/PNS applied alone with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours, or intensities up to 300% of sensory threshold when C/PNS is paired with TMS. All of these parameters of stimulation and procedures have safely been used as previously reported in the literature. Sham stimulations were delivered for each modality as scientifically needed. Some sessions included recording of behavior or brain activity (such as behavioral testing, MRI, and MEG) if brain stimulation targets were unknown. This information was used to inform the design of brain stimulation protocols.~Each subject was able to participate in up to one experimental session per day, and up to 20 total sessions over a twenty year period under this protocol. A single session lasted no longer than 8 hours. Appropriate rest breaks and meal breaks occured during long sessions. CTDB was used to track the number of sessions per subject to ensure they did not exceed 20 sessions. Protocol AIs were responsible for entering the subjects/sessions into CTDB.~We previously tested the effects of different forms of stimulation on motor cortical excitability, cognitive and motor behavioral tasks, and brain state measures derived from neuroimaging data (i.e. - MRI, fMRI, MEG and EEG). Stimulation was be applied before, after, or during physiological (i.e. motor evoked potentials, M-wave, F-wave, or H-Reflexes), neuroimaging or behavioral measures.~Outcome Measures~No new outcome measures are proposed. Changes in motor cortical excitability were previously measured as the change in the average peak-to-peak amplitude of a motor evoked potential (MEP) as measured with EMG. Neuroimaging measures included changes in oscillatory brain activity power as measured with EEG or MEG, changes in BOLD fMRI activation or changes in functional connectivity (i.e. covarying fluctuations in BOLD or spectral power across the brain). Behavioral outcome measures focused on changes in performance as a function of learning, or as a function of applied brain stimulation.

Objectives~Noninvasive stimulation of the central and peripheral nervous system, including transcranial magnetic stimulation (TMS), transcranial direct and alternating current stimulation (tDCS and tACS, respectively) and cutaneous/peripheral nerve stimulation (C/PNS) alone or paired with TMS (paired associative stimulation, PAS), has been increasingly used in the investigation of cortical plasticity and as a possible adjuvant strategy in neurorehabilitation. It has been shown that TMS, tDCS, tACS and C/PNS can modulate motor function in healthy volunteers, as well as in patients with neurological disorders such as stroke.~One fundamental problem is that the optimal parameters of stimulation to modulate motor function by all of these techniques are not known. The purpose of this protocol is to explore within safe guidelines, the effects of different stimulation parameters on motor cortical function, on oscillatory brain dynamics measured with magnetoencephalography (MEG) and electroencephalography (EEG), on eye movements, and on fMRI activation. In addition, this protocol will be used to train new fellows coming to NINDS Human Cortical Physiology Section (HCPS) in the use of TMS, tDCS, tACS and C/PNS techniques.~We expect that information emerging from these studies will allow us to 1) optimize experimental protocols or stimulation parameters to collect pilot data in healthy volunteer for future patient-oriented hypothesis-driven protocols,2)to collect pilot data for power analysis for future patient-oriented hypothesis driven protocols, and 3) to train new fellows in the use of these different methods.~Study Population~Up to 1500 healthy volunteers, age 18 and older.~Design~Healthy volunteers will receive one or more of the following types of stimulation alone or in combination: (1) single- and paired-pulse TMS with inter-stimulus intervals of greater than 1s and up to 20s and intensities of up to 100% of stimulator output; (2) 1 Hz TMS for up to 30mins and up to 115% of resting motor threshold (RMT) intensity; (3) tDCS applied at an intensity of up to 4 mA for a duration of up to 60mins, as long the total charge does not exceed 7.2 C; (4) tACS applied at a peak-to-peak intensity of up to 4 mA for a duration of up to 60 minutes, minutes, as long the total charge does not exceed 7.2 C; (5) C/PNS applied alone with intensities below 130% of the peripherally-elicited-motor-threshold for up to 2 hours, or intensities up to 300% of sensory threshold when C/PNS is paired with TMS. All of these parameters of stimulation and procedures have safely been used as previously reported in the literature. Sham stimulations will be delivered for each modality as scientifically needed. Some substudies may involve recording of behavior or brain activity only (such as behavioral testing, MRI, and MEG) if brain stimulation targets are unknown. This information can help design future brain stimulation protocols.~Each subject may participate in up to 20 sessions. A single session may last no longer than 8 hours to allow for initial testing paradigm followed by retests or performing other components of the same substudy later in the day. Appropriate rest breaks and meal breaks will occur during long sessions. Subjects participate in one experimental session per day under this protocol. The 20 experimental sessions will be scheduled over a twenty-year period. CTDB is used to track the number of sessions per subject so it does not exceed 20 sessions. The AIs are responsible for entering the subjects/sessions into CTDB.~We will test the effects of these different forms of stimulation on motor cortical excitability, cognitive and motor behavioral tasks, and brain state measures derived from neuroimaging data (i.e. - MRI, fMRI, MEG and EEG). Stimulation may be applied before, after, or during physiological (i.e. motor evoked potentials, M-wave, F-wave, or H-Reflexes), neuroimaging or behavioral measures.~Under this protocol, we conduct:~Exploratory Sub-studies: These substudies are exploratory in nature and are conducted in order to develop information to generate better informed future hypotheses and/or power analyses. We have set an upper limit of 40 subjects per sub-study.~Hypothesis-Testing Sub-studies: Hypothesis-testing sub-studies are studies with specific hypotheses to be tested. These sub-studies undergo statistical and PIRC review after 6 subjects per group (e.g., after 12 subjects, 6 per arm, if two groups are studied), before additional subjects can be recruited. Together, the P.I. and PIRC will decide whether to continue the sub-study with more subjects without an amendment or whether an amendment or protocol would be necessary. A memo requesting a review of hypothesis-testing sub-studies for possible additional enrollment (beyond 6) will be sent to PIRC and the statistical reviewer.~This protocol is ...

Linear flow during cardiopulmonary bypass (CPB) frequently induces renal damage.~We will evaluate whether automatic intra-aortic balloon pump (IABP) induced pulsatile perfusion preserves renal function in patients undergoing myocardial revascularization at different risk for renal damage.~100 patients undergoing preoperative IABP will be stratified for renal function.~Intervention. The patients will be randomized to non-pulsatile CPB during cardioplegic arrest or automatic IABP induced pulsatile CPB.~Renal function, daily diuretics, complication rate, lactatemia and other biochemical indices will be compared in patients.~We will prospectively enrolle 100 patients undergoing isolated primary high-risk coronary artery bypass grafting for severe left main stem disease (70% narrowing) or left-main equivalent three-vessels coronary disease. On admission to our institution, the patients will be stratified for renal function according to KDOQI and randomly assigned to Group A or Group B. We will exclude from the study patients older than 75 years, and/or with kidney disease ≥ Stage 4 (GFR 15 - 29 ml/min/1.73 m2), and/or with other splanchnic organ comorbidities (liver or mesenteric impairment, abdominal aortic aneurysm, abdominal arteries vasculopathy), and/or severe autoimmune disease.~The patients randomized to Group A (n=50) will receive a preoperative IABP treatment before induction of anesthesia, with IABP turned off during cardioplegic arrest, and restarted with a 1:1 IABP mode immediately after cross-clamp removal (as is the traditionally adopted perioperative IABP support); the other 50 (Group B) will receive standard preoperative treatment with IABP, which will switche into an automatic 80 bpm mode during cross-clamp time, and switche again into a 1:1 IABP after cross-clamp removal, in order to achieve a pulsatile perfusion during the entire intra-operative time-course.~The patients will be stratified in 2 subgroups according to the preoperative renal function: a subgroup will include 64 patients (32 allocated in Group A and 32 in Group B) with stage 1 or 2 [Stage 1: GFR ≥90 ml/min/1.73 m2 - Stage 2: GFR 60 - 89 ml/min/1.73 m2] and therefore considere at lower-risk for post-CPB renal damage; the remaining 36 (18 for each group) with KDOQI Stage 3 of kidney disease (GFR 30 - 59 ml/min/1.73 m2) will be considered at higher-risk for perioperative renal complications [19].~The study protocol has been approved by the institution's Ethical Committee/Institutional Review Board, and informed consent will be obtained from each patient.~Anesthesia Anesthetic technique will be standardized: induction will consiste of i.v. propofol infusion (3 mg/kg) combined with fentanyl (0.10 mg/Kg). Neuromuscular blockade will be achieved by 4 mg/h pancuronium bromide, and lungs will be ventilated to normocapnia with air and oxygen (45-50%). Propofol infusion (150-200 μg/Kg per min) and isoflurane (0.5% inspired concentration) will maintaine anesthesia. Inotropes will be started immediately after aortic cross-clamp removal to maintain adequate mean systemic pressure, always starting with enoximone at a dosage of 5 μg/Kg/min. The need for further increase in inotropes will be record: inotropes will be defined as low-dose when enoximone will be administered at a dosage 5 μg/Kg/min, medium-dose when enoximone will be between 6 and 10 μg/Kg/min, or dobutamine will add at a dosage between 5 and 10 μg/Kg/min, and high-dose when enoximone or dobutamine will be >10 μg/Kg/min or epinephrine add at any dose.~Surgical technique and cardiopulmonary bypass According to our Institutional policy we will insert IABP (7.5 or 8 Fr, 34 or 40 ml according to the body surface area; balloon Datascope Corp., Fairfield, NJ, connected to a Datascope pump [Datascope Corp, Fairfield, NJ]) percutaneously with the sheetless technique, through the best femoral artery, before induction of anesthesia, in order to better support the perioperative hemodynamic of patients undergoing surgery for severe left main stem or 3-vessels left-main equivalent disease. The correct placement of IABP will be always assessed by postoperative chest X-ray or transesophageal echocardiography. Patients will receive anticoagulation with enoxaparin, with a target activated partial thromboplastin time >40 seconds, starting when the postoperative bleeding was controlled (usually within 6 hours). IABP will be withdrawn when hemodynamic stability will restore (i.e., a cardiac index 2.0 L/m2 per minute with only minimal pharmacologic inotropic support, dobutamine or enoximone at 5 µg/kg per minute). CPB and surgical techniques will be standardized and not changed during the study period. Heparin will be given at a dose of 300 IU/kg to achieve a target activated clotting time of 480 seconds or above. Blood recovery with an autotransfusion device (Autotrans Dideco, Mirandola, Modena, Italy) will be performed intraoperatively in all cases. A level of hemoglobin lower than 8 g/dl will be used as an indication for blood transfusion. Standard CPB circuit will be used. The extracorporeal circuit will be primed with 1000 ml of Ringer's Lactate solution and 40 mg of heparin. Systemic temperature will be kept between 32 and 34° C. Myocardial protection will be achieved with intermittent antegrade and retrograde hyperkalemic blood cardioplegia. Total CPB flow will be maintained at 2.6 L/min-1/m-2. In Group A patients, IABP will be turned off during cardioplegic arrest, maintaining a standard non-pulsatile CPB; Group B patients will undergo IABP-induced pulsatile CPB during cardioplegic arrest, with pulsatile flow maintained by an automatic 80 bpm mode until aortic declamping.~Endpoints The primary endpoint of this study is the evaluation of the renal function as assessed by measuring GFR in the perioperative period. In all patients will be evaluated perioperative renal function, in-hospital mortality and morbidity, and complications, in-hospital and intensive therapy unit (ITU) stay, IABP-related complications. Renal function is primarily evaluated by GFR calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) study equation, recommended by KDOQI as the preferred equation for the calculation of GFR in adults (taking into account serum creatinine, age, race, gender) [22] and, secondarily, by other indices, such as urine output, need for diuretics, blood urea nitrogen (BUN). Plasma lactate concentrations will be measured to indirectly assess the adequacy of tissue perfusion [20] Acute renal insufficiency (ARI) is defined as a decrease greater than 50% over preoperative value of calculated GFR. Acute renal failure (ARF) is defined as any postoperative renal insufficiency requiring first-time hemofiltration, dialysis or any other renal replacement therapy (RRT). In-hospital mortality is defined as any death occurring during hospital stay or in the first 30 postoperative days. Hospital morbidity is defined as any complication requiring specific therapy or causing a delay in hospital or ITU discharge. IABP-related complications is defined as any aortic dissection or perforation, limb or mesenteric ischemia, or infection or hemorrhage at the balloon entry point.~Biochemical analysis All patients will undergo pre- and perioperatively routine laboratory investigations, including standard hemogram, serum levels of creatinine, urea nitrogen, calcium, phosphate, glucose, albumin, electrolytes, albumin, transaminases, -glutamyl-transpeptidase, lactic acid dehydrogenase, bilirubin, acid-base parameters, troponin I and lactic acid. The determinations of the majority of these parameters will be conducted preoperatively before anesthetic induction, and at 12, 24, 48, and 72 hours postoperatively. In order to evaluate the adequacy of myocardial protection techniques, Troponin I will be measured on coronary sinus blood samples, obtained from the retrograde cardioplegic cannula, 10 minutes following completion of proximal anastomoses. The Troponin I assays will be carried out using diagnostic kits provided by Beckman Coulter (Fullerton, California; AccuTnITM Access Immunoassay System).~Statistical analysis Statistical analysis will be performed by the SPSS program for Windows, version 10.1 (SPSS Inc, Chicago, IL). Continuous variables will be presented as mean ± standard deviation, and categorical variables as absolute numbers and/or percentages. Data will be checked for normality before statistical analysis. Normally-distributed continuous variables will be compared using the unpaired t test, whereas the Mann-Whitney U test will be used for those variables that are not normally distributed. Categorical variables will be analyzed using either the chi-square test or Fischer's exact test. Comparison between and within groups will be made using two-way analysis of variance for repeated measures. Comparisons will be considered significant if p<0.05.

Linear flow during cardiopulmonary bypass (CPB) frequently induces renal damage.~We will evaluate whether automatic intra-aortic balloon pump (IABP) induce pulsatile perfusion preserves renal function in patients undergoing myocardial revascularization at different risk for renal damage.~100 patients undergoing preoperative IABP will be stratified for renal function.~Intervention. The patients will be randomized to non-pulsatile CPB during cardioplegic arrest or automatic IABP induced pulsatile CPB.~Renal function, daily diuretics, complication rate, lactatemia and other biochemical indices will be compared in patients.~We will prospectively enrolle 100 patients undergoing isolated primary high-risk coronary artery bypass grafting for severe left main stem disease (70% narrowing) or left-main equivalent three-vessels coronary disease. On admission to our institution, the patients will be stratified for renal function according to KDOQI and randomly assigned to Group A or Group B. We will exclude from the study patients older than 75 years, and/or with kidney disease ≥ Stage 4 (GFR 15 - 29 ml/min/1.73 m2), and/or with other splanchnic organ comorbidities (liver or mesenteric impairment, abdominal aortic aneurysm, abdominal arteries vasculopathy), and/or severe autoimmune disease.~The patients randomized to Group A (n=50) will receive a preoperative IABP treatment before induction of anesthesia, with IABP turned off during cardioplegic arrest, and restarted with a 1:1 IABP mode immediately after cross-clamp removal (as is the traditionally adopted perioperative IABP support); the other 50 (Group B) will receive standard preoperative treatment with IABP, which will switche into an automatic 80 bpm mode during cross-clamp time, and switche again into a 1:1 IABP after cross-clamp removal, in order to achieve a pulsatile perfusion during the entire intra-operative time-course.~The patients will be stratified in 2 subgroups according to the preoperative renal function: a subgroup will include 64 patients (32 allocated in Group A and 32 in Group B) with stage 1 or 2 [Stage 1: GFR ≥90 ml/min/1.73 m2 - Stage 2: GFR 60 - 89 ml/min/1.73 m2] and therefore considered at lower-risk for post-CPB renal damage; the remaining 36 (18 for each group) with KDOQI Stage 3 of kidney disease (GFR 30 - 59 ml/min/1.73 m2) will be considered at higher-risk for perioperative renal complications [19].

Since many individuals with mild cognitive impairment (MCI) appear to function normally, MCI may often be recognizable through testing in advance of any changes noticed by family members or caregivers. Early and frequent testing can therefore trigger an earlier diagnosis, which may increase the effectiveness of currently available medications used to delay onset of Alzheimer's symptoms. Primary care and geriatric physicians currently lack the necessary tools required for quick and accurate MCI screening in the doctor's office environment. The current industry-standard is a battery of pen & paper neuropsychological tests that require 1.5 hours in a quiet room with a neuropsychologist.~Comparison: virtual reality display device compared to the standard neuropsychological evaluation for detecting mild cognitive impairment (problems with memory, concentration, reaction time, etc.).

The purpose of this research study is to compare a virtual reality display device with the standard neuropsychological evaluation for detecting mild cognitive impairment (problems with memory, concentration, reaction time, etc.).

Total joint replacements are some of the most successful medical devices developed over the last fifty years. They enable millions of people to remain ambulatory and pain free, with minimal risk. In 2002, over 200,000 total hip replacements, 350,000 total knee replacements, and 25,000 total or partial shoulder replacements were performed in the United States (HCUP data). Future use will likely be even higher: it is estimated that by the year 2020, the population 65 and over in developed countries will increase by 71%. Existing studies do not provide adequate prospective data to evaluate long-term outcomes. Most health related quality of life studies in THA and TKA only report data up to twelve months post-operatively. In addition, most large studies of TKA and THA have been performed in Medicare patients. While these databases are important in providing population based data, Medicare studies do not permit any direct patient contact, and provide no information on patients under 65.~Existing studies have also investigated predictors of patient outcome at one and two years after joint arthroplasty. However, very little is known about predictors of prosthesis failure, and there are no validated clinical indicators for choosing one prosthesis model over another. Once a device is FDA approved, there is very little motivation on the part of the developer to perform complete post-marketing research, despite the importance of these data to the public health. Most existent studies are not powered to compare differences between models.~The purpose of this study is to establish a prospective cohort of HSS total knee arthroplasty.~The creation of large prospective joint arthroplasty cohorts responds directly to initiatives proposed in the NIH Consensus Development Conferences on Total Knee Replacement. This study will allow in depth analysis from the Provider and Health Care System Perspective, (one of the important research perspectives advocated by the NIH), including surgeon, surgical technique, type of prosthesis, implantation technique and perioperative care. We will be able to evaluate all patients who receive arthroplasty surgery at HSS, as opposed to a convenience sample, and we will be able to follow patients for the life of their joint replacement. We will also be able to asses patient-level factors affecting outcomes, including medical and socio-demographic characteristics, participation in rehabilitation services, the extent of social support, and the level of patients' physical activity.~The consensus conference emphasized the importance of evaluating the use of TJA in younger patients, as these patients are underrepresented in most existing studies. For example, in one of the most rigorous existing studies of TKA, patients were followed for two years after surgery. However, three centers were needed to recruit 860 TKA patients, whose mean age was 70. By contrast, HSS alone performed over 2,000 total knee replacement surgeries in 2004, of which 41% were in patients under 65 years of age, and 28% were in patients under 60 years.

Total joint replacements are some of the most successful medical devices developed over the last fifty years. They enable millions of people to remain ambulatory and pain free, with minimal risk. In 2002, over 200,000 total hip replacements, 350,000 total knee replacements, and 25,000 total or partial shoulder replacements were performed in the United States (HCUP data). Future use will likely be even higher: it is estimated that by the year 2020, the population 65 and over in developed countries will increase by 71%. Existing studies do not provide adequate prospective data to evaluate long-term outcomes. Most health related quality of life studies in THA and TKA only report data up to twelve months post-operatively. In addition, most large studies of TKA and THA have been performed in Medicare patients. While these databases are important in providing population based data, Medicare studies do not permit any direct patient contact, and provide no information on patients under 65.~Existing studies have also investigated predictors of patient outcome at one and two years after joint arthroplasty. However, very little is known about predictors of prosthesis failure, and there are no validated clinical indicators for choosing one prosthesis model over another. Once a device is FDA approved, there is very little motivation on the part of the developer to perform complete post-marketing research, despite the importance of these data to the public health. Most existent studies are not powered to compare differences between models.~The purpose of this study is to establish a prospective cohort of HSS total knee arthroplasty.

During and six months after treatment with peginterferon alpha and ribavirin strict use of birth control is recommended (the producers advice two reliable forms) for both men and women because ribavirin has teratogenic and/or embryo-lethal effects in animal studies.~In cases of pregnancies during paternal exposure to peginterferon alpha and ribavirin elective termination of the pregnancy is usually recommended. However three cases of births after paternal exposure are reported with no birth defects. Cases of abnormalities after paternal exposure to ribavirin are lacking.~Also studies on the influence of ribavirin on sperm in human are lacking.~The aim of this study is to study the effect of peginterferon alpha and ribavirin on spermatozoa in men using these medication.

The aim of this study is to study the effect of peginterferon alpha and ribavirin on spermatozoa.

The following opportunity is a reserach project at the American University Behavioral Pharmacology and Health Promotions Laboratory (BPHP). The study population is 11-17 year olds. The 30 minute online survey asks questions about behavior, sleep, and typical food consumption. The purpose of this survey is to better understand these habits in young people and the effects of these habits on behavior and sleep. This information will provide us with a better understanding of the daily habits in young people and guide the direction of future research projects.

Online survey for 11-17 year olds about behavior, sleep, and food consumption patterns. This survey can be completed on any computer that has internet access.

Amniotic fluid embolism is a rare devastating thromboembolic event, which is probably caused by the entrance of amniotic fluid (AF) to the maternal circulation. While AF contains coagulation activators, their role during pregnancy has not been elucidated. The current study aimed to evaluate coagulation parameters in AF during human pregnancy.

Amniotic fluid embolism is a rare devastating thromboembolic event, which is probably caused by the entrance of amniotic fluid (AF) to the maternal circulation. While AF contains coagulation activators, their role during pregnancy has not been elucidated. The current study aimed to evaluate coagulation parameters in AF during human pregnancy.

In a recent fMRI study (Makin TR. et al., J. Neurosci. 2007), we found extended cortical representation for a visual stimulus provided that it is presented close to the hand. It is therefore interesting to ask whether changes in the brain following limb amputation might induce changes in the amputees' perception of the body and consequently it's surrounding. In this study, we wish to find behavioral evidence for the question whether an amputation of the arm can lead to changes in visual perception or motor responses to objects in peripersonal space. We hypothesize that changes in the motor and somatosensory hand-related cortices following amputation might lead to changes in parietal hand-related areas. Consequently, we expect to find reduced perception/attention/responses to hand-related objects in the space ipsilateral to the amputation.~In this experiment we plan to employ a paradigm which is inspired by the affordance effect, originally introduced by Tucker and Elice (1998): we will present subjects with brief images of either manipulable or non manipulable objects in either the left or right visual field. The subjects will be required to determine whether the object contains a metal or not, by moving either their left or their right shoulder. We predict that while the control group of normal subjects would show a congruency effect (that is superior performance (faster and more accurate responses) when the responding shoulder is congruent with the position of the objects, the amputees will show spatial biases towards the non-amputated side. This effect should be more prominent for the manipulable objects.

In this study, we wish to find behavioral evidence for the question whether an amputation of the arm can lead to changes in visual perception or motor responses to objects in peripersonal space. We hypothesize that changes in the motor and somatosensory hand-related cortices following amputation might lead to changes in parietal hand-related areas. The consequence of these parietal changes should be reflected behaviorally in reduced perception/attention/responses to hand-related objects in the space ipsilateral to the amputation. We further hypothesize that the use of prosthetics may provide the necessary visual feedback to maintain an intact hand representation and therefore lead to lesser cortical reorganization in both visual and somatosensory cortical areas.

The study will be a double blind, randomized, placebo controlled trial conducted in men 19-65 years of age. Participants will receive daily zinc or placebo liquid supplements for 21 days. Supplemental zinc will be given as zinc sulfate; the lower dose zinc supplement will contain 10 mg/d elemental zinc, and the higher dose zinc supplement will contain 20 mg/d elemental zinc. The placebo will contain the same excipients expect for zinc sulfate.~Multiple blood draws will be performed throughout the course of the study, to determine the responsiveness of plasma zinc concentrations to zinc supplementation. Two baseline blood draws will occur prior to the start of supplementation (study days -7 and 0). Blood draws will be performed on days 1, 2, 5, 9, 14 and 21 of the 21 day supplementation period. Upon termination of supplementation (day 21), blood draws will be performed on days 1, 2, 5, 9, 14 and 21 post-supplementation (study days 22, 23, 26, 30, 35 and 42).~The major outcomes of interest are the magnitude and velocity of change in plasma zinc concentration. Other outcomes to be assessed are plasma concentrations of the acute phase proteins CRP and AGP, as well as reported morbidity, because of their potential roles as confounding variables. Anthropometric variables will be assessed at baseline.

This is a double-blind, randomized controlled trial conducted in men 19-65 years of age who will receive daily zinc supplements (10 or 20 mg zinc/d as zinc sulfate) or placebo for 21 days. Blood samples for plasma zinc and CRP concentrations will be drawn at baseline and days 1, 2, 5, 9, 14, and 21 during supplementation and days 1, 2, 5, 9, and 14 after discontinuation of supplementation.

Introduction: An increasing number of patients undergo surgery for degenerative spine disease, which is, however, related to a significant development of postoperative complications. Evidence has been gathered for other surgical procedures about improved outcome after early rehabilitation programs (fast track surgery), preoperative smoking and alcohol cessation programs, respectively. Hitherto, no studies have been published concerning a combined program of the preoperative prevention programs and fast track surgery.~Aim: The aim is to evaluate the outcome after spine surgery when using an integrated program that combined preoperative prevention and early postoperative rehabilitation compared to the routine procedures.~Outcome measurements: Postoperative hospital stay, complications, function, pain, and patient satisfaction.~Method: 60 patients scheduled for surgery for degenerative lumbar disease were computer-randomized to intervention. The control group followed the routines in the department. The intervention group followed the integrated program consisting of preoperative prevention, which began 2 months prior to the operation: an exercise program designed to strengthen the muscles of the spine, and optimization of the analgetic treatment. Smokers and harmful drinkers were offered cessation intervention. The day before surgery all had enteral protein supplement.~Early postoperative rehabilitation included balanced pain therapy, including self-administered epidural analgesia, intensified mobilization immediately after surgery and enteral protein supplement.

Aim: The aim is to evaluate the outcome after spine surgery when using an integrated program that combined preoperative prevention and early postoperative rehabilitation compared to the routine procedures.~Outcome measurements: Postoperative hospital stay, complications, function, pain, and patient satisfaction.~Method: 60 patients scheduled for surgery for degenerative lumbar disease. The control group followed the routines in the department. The intervention group followed the integrated program consisting of preoperative prevention.

Morbidity in the post operative phase of thoracotomies is characterised by pain, dyspnea, shoulder dysfunction and a loss of exercise tolerance may occur. There is literature about post-thoracotomy painsyndromes and postoperative quality of life has been investigated. However, data on post-thoracotomy rehabilitation and influence on morbidity and recovery are not available.~Aim of the study:~Primary: To evaluate the effects of an integrated multidisciplinary rehabilitation program on health related quality of life in the 12 months postoperative period in patients with an elective thoracotomy.~Secondary: To evaluate the effects of the program on general quality of life (SF-36), acute/chronic post-thoracotomy pain, impairment (changes in pulmonary function), disability (exercise capacity) and start to complete recovery (ECOG score of 0 or 1) 12 months postoperatively in patients with an elective thoracotomy.~Study design: prospective single-centre, open randomised trial. Eighty-eight elective thoracotomy patients with an age between the 18 and 80 years will be recruited during two years. The follow up for each patient will be one year. The exclusion criteria are chronic pain involvement, a previous thoracotomy, comorbidity limiting rehabilitation, psychiatric illness and non- compliance.~Patients will be asked for participation before thoracotomy by informed consent and will be randomised post-thoracotomy, before discharge into a rehabilitation or 'regular care' group. Randomisation will take place for rehabilitation or regular care by a minimisation program with special attendance to age (< 70 or ≥ 70 years), gender, the result of the 6 minute walk test (< 100 m or ≥ 100 m), the FEV (FEV1< 40% or ≥ FEV1 40 %) and type of surgery (pneumectomy vs other). During screening a spirometry and a 6 minute walk test will be performed. The first questionnaires (VAS, McGill pain questionnaire) will be given to the patients after enrolment and before thoracotomy. The post-thoracotomy pain management consists of the standard analgetic treatment; a thoracic epidural catheter which will be slowly replaced by paracetamol, opioids and NSAID's. The consumption of analgetics will also be documented in the follow up. Supplementary oxygen and lung inhalation is given when necessary. This will be scored too. Regular physical therapy will be started directly after thoracotomy as soon as possible.~The rehabilitation program will be initiated within a month after discharge. The degree of the rehabilitation program will be separately detected for each patient by a cycle test (heart rate) within 3 weeks post-thoracotomy. Patients in the pulmonary rehabilitation program will be guided by a multidisciplinary team of pulmonologist, physical therapist and social worker during 12 weeks. The program will last 3 x 2 hours weekly consisting of exercise training and education.~All patients will be followed up after discharge at 1 month, 3 months, 6 months and 12 months at the outpatient clinic of the pulmonology department and the pain clinic of the anaesthesia department. Before discharge and at these intervals (except for the SGRQ at 1 month), patients have to fill questionnaires about quality of life (SF-36 and SGRQ) and pain (McGill pain questionnaire and VAS). Exercise capacity by means of the 6 minutes walk test and spirometry will be measured after the accomplishment of the rehabilitation program at 3 months.~During follow up all the results between the experimental rehabilitation group and the regular care group will be compared. In the interpretation of these results start to complete recovery is defined as ECOG 0 and 1.~Randomisation, blinding and treatment allocation Randomisation will take place for rehabilitation or regular care by a minimisation program with special attendance to age (< 70 or ≥ 70 years), gender, the result of the 6 minute walk test (< 100 m or ≥ 100 m), the FEV1 (FEV1< 40% or ≥ FEV1 40 %), and type of surgery (pneumectomy vs other).~Study population:~Eighty-eight patients with an elective thoracotomy between the age of 18 and 80 years.~Intervention:~An early pulmonary rehabilitation program during 12 weeks initiated after discharge from the hospital.~Inclusion criteria:~elective, thoracotomy patients with a surgical intention to cure.~age between 18 and 80 years.~ECOG 0 - 2 post-thoracotomy.~Exclusion criteria:~patients with chronic pain.~a previous thoracotomy.~comorbidity limiting rehabilitation.~non-compliance.~Main study endpoints~1. health related quality of life (SGRQ score). Secondary study endpoints~general quality of life (SF-36).~acute / chronic post-thoracotomy pain (McGill and VAS).~impairment (changes in pulmonary function).~disability (exercise capacity; 6 Minute Walking Distance).~start to complete recovery (ECOG score of 0 or 1).~Statistical analysis: All analysis will be on an intention-to-treat basis. The primary analysis will be on an intention-to-treat basis. The mean change in the primary endpoint (SGRQ total score) after 6 months between the groups will be analysed using unpaired t-tests. These tests will also be used to analyse differences after 12 months in secondary endpoints (SF-36 scores, 6-minute walking difference, pain scores, and lung function values). Since some study endpoints (quality of life and pain scores) will be measured more than two times (repeatedly measured) the course of these scores in time will be tested using MANOVA-analysis. To test for differences in proportions (proportion of patients with an ECOG-score of 0 or 1 after rehabilitation) the Chi2 -test will be used.~Burden and risks associated with participation:~There are no adverse effects due to the rehabilitation program. Patients in the 'regular care' group will not be guided by the multidisciplinary rehabilitation team. The disadvantages are the following: Patients have to fill in quality of life questionnaires, pain questionnaires and have to evaluate painscales (SGRQ, SF-36; McGill Pain questionnaire and VAS) have to perform the 6 minutes walk-test and a spirometry twice. Finally, patients have to visit the pulmonologist and the pain clinic more frequently. The expected benefits are a better exercise tolerance, less pain and a better quality of life; a faster recovery.

The purpose of this study is to evaluate the effects of an integrated multidisciplinary rehabilitation program on health related quality of life in the 12 months postoperative period in patients with an elective thoracotomy and to evaluate the effects of the program on general quality of life (SF-36), acute/chronic post-thoracotomy pain, impairment (changes in pulmonary function), disability (exercise capacity) and start to complete recovery (ECOG score of 0 or 1) 12 months postoperatively in patients with an elective thoracotomy.

This is a multi-center, open-label (doctors and patients know which drug is being given), Phase IIIb clinical trial to evaluate the effectiveness, safety and tolerability of the combination of PREZISTA (darunavir)/ritonavir and TMC125 when substituted for enfuvirtide, current protease inhibitor(s) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI(s)) in antiretroviral resistant patients with viral suppression but who are intolerant of enfuvirtide. This study will be conducted in the U.S. at up to 5 sites where 40 patients will receive PREZISTA (darunavir) /ritonavir twice daily (600/100mg) and TMC125 (200 mg) twice daily over a 48-week treatment period.~The study will consist of a total of 11 patient visits. At the screening visit (Week -1 to -6) blood will be collected from patients to determine eligibility. Once all data are available to determine the eligibility of the patient, the baseline visit will be scheduled and trial treatment initiated at this visit. The Baseline Visit (Day 1) will be followed by a 48-week treatment period. The patient will be evaluated at Weeks 2, 4, 8, 12, 16, 24, 36, and 48. Patients will be asked to return for a 2-week follow up visit at Week 50.~Treatment will include PREZISTA (darunavir) /ritonavir and TMC125 plus continued nucleosides. The patient must continue all existing nucleosides in their background regimen for the duration of the study.~During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for efficacy and safety will be done at regular visits. Study patients will receive oral (by mouth) PREZISTA (darunavir) 600 mg and 100 mg of ritonavir twice a day in combination with TMC125 200mg orally twice a day for 48 weeks.

The purpose of this study is to examine the safety, tolerability, and effectiveness of darunavir/ritonavir combined with TMC125 when current protease inhibitor(s), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI(s)) and enfuvirtide are replaced by darunavir/ritonavir and TMC125 in HIV positive patients who can no longer tolerate enfuvirtide and are experiencing viral suppression. Other antiviral drugs in the regimen are to remain unchanged.

In the United States, racial and ethnic minorities suffer disproportionately from preventable diseases and conditions. Many of these problems result from health-related behaviors that are established during childhood and adolescence. Latino and African-American adolescents are at considerable risk for the negative health consequences of early, risky sexual activity. This study will focus on inner-city Latino and African-American adolescents in grades 6, 7, and 8. The primary aim will be to develop an intervention that parents can use to address the issue of sexual risk behavior with their children.~The intervention will take place in a primary health care clinic when mothers accompany their children for annual physical exams. Mothers will meet with a social worker for approximately 25 minutes while their children are being examined by the physician. During this time, mothers will receive information about the problem of premature adolescent sexual activity, support in preventing or reducing their children's sexual risk behavior, instruction about how to talk with their children about sexual risk behavior, and targeted homework activities. All parents will also receive three follow-up phone calls to increase the probability that the homework tasks will be completed.~Participants in this study will also be assigned to one of the following three groups: an experimental group; an active control group; or a passive control group. Participants in all groups will complete three questionnaires over the course of the study to assess outcomes. Participants in the experimental and active control groups will partake in an additional meeting with a clinic social worker. Parents in the experimental group will meet with the social worker to discuss effective parent-adolescent communication strategies. They will also receive take-home materials to help them communicate with and parent their adolescents to reduce sexual risk behavior. Parents in the active control group will meet with the social worker to discuss adolescent nutrition and receive informational brochures.~Three booster sessions will take place via telephone for parents in the experimental and active control groups. The first booster call will occur approximately 1 month after study entry, the second will occur 5 months after the intervention ends, and the third will occur 9 months post intervention. No such booster calls will be provided to parents in the passive control condition.

This study will evaluate the effectiveness of a parent-based intervention in reducing sexual risk behavior in high-risk Latino and African-American adolescents.

People are advised to engage in weight-bearing physical activity to help prevent the loss of bone and muscle mass that occurs with aging. There is evidence from studies of animals that non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, block some of the bone- and muscle-building effects of exercise. The aim of this study is to determine whether use of ibuprofen, either before or after exercise, blocks the benefits of exercise training on bone and skeletal muscle in older women and men. The hypothesis is that taking ibuprofen before exercise will block some of the effects of exercise training to increase bone density and muscle mass.~Women and men aged 60-75 years will complete a supervised, 9-month exercise training program designed to increase bone and muscle mass. The training will include weight lifting and weight-bearing exercises, such as jumping in place and treadmill walking, up to 5 days per week. Participants will be randomly assigned to take 1 of 3 study pill combinations before and after each exercise session. The combinations of study pills will be: placebo before/placebo after, placebo before/ibuprofen after, or ibuprofen before/placebo after. The dose of ibuprofen will be 400 mg. Bone density of the hip and spine, body composition (total body muscle and fat), and markers of bone turnover in the blood will be measured before and after 4.5 and 9 months of training. Muscle cross-sectional area of the thigh will be measured by CT before and after 9 months of training. A subset of participants will have biopsies of the thigh muscle before and after training to measure proteins and genes associated with muscle build-up and breakdown.~Volunteers who do not use ibuprofen, aspirin, or acetaminophen more than 3 days per month will be enrolled. People with intolerance to ibuprofen or related drugs, cardiovascular disease, or orthopedic problems that limit exercise will be excluded from the study.

The purpose of this study is to determine if the use of ibuprofen blocks the benefits of exercise to build bone and muscle mass.

A study of an electronic voting system as a learning aid during tutorials. This study was undertaken with clinical students over a one year period of observation

A study of an electronic voting system as a learning aid during tutorials

Background The small bowel has been a large blind spot for gastrointestinal (GI) endoscopy as, until recently, the small bowel was not accessible with conventional endosocopes.~Double-balloon enteroscopy (DBE) is a novel endoscopic procedure for visualising the entire small bowel. The method was first described by Yamamoto et al. and May et al in 2001 and 2003, respectively (1,2). Since then, DBE has spread to a rising number of centres around the world. Both endoscopic diagnosis (e.g. by biopsy) and treatment can be easily performed using DBE. The first larger series, recently published, demonstrate that DBE is feasible in scoping large parts of the small bowel, with total small intubation possible in about 30-40% of cases (3,4).~In any GI endoscopy procedure it is mandatory to insufflate gas into the bowel to secure good visualisation. All endoscopes used for GI endoscopy provide a gas insufflation unit. The gas is pumped on demand into the area examined by the endoscopist via a gas tube incorporated in the endoscope. Currently, air is used for this purpose in more than 90% of centres throughout the world. The use of air, however, is far from ideal to use for insufflation in GI endoscopy. After GI endoscopy, significant amounts of air are usually retained in the bowel segment inspected (5). This air has to pass the GI tract and exit physiologically through the rectum. Thus, abdominal pain and discomfort during and after the examination due to the retention of air has been shown to be very common during and after endoscopic procedures (5-9).~Carbon dioxide gas (CO2), unlike air, is rapidly absorbed from the bowel. Within minutes, several litres of CO2 can be absorbed from the GI tract. The use of CO2 has been shown to result in more comfortable examinations in both colonoscopy and flexible sigmoidoscopy in several randomised trials (6-9). In these studies, CO2 insufflation almost completely reduced procedure-related pain and discomfort.~To our knowledge, no research has been performed investigating the use of CO2 in DBE. DBE is a long-lasting procedure (mean examination time 75 minutes (4)). Large volumes of air are insufflated during the procedure, leading to significant distension of the small bowel during and after the examination.~One of the main technical difficulties in DBE is the formation of small bowel loops and scarp angels during deep intubation of the endoscope. These loops and angels are the major restriction to deep intubation of the endoscope. Loops and scarp angels are more pronounced in air-distended bowel segments.~The aim of the present study is to examine whether CO2 insufflation leads to a reduction of abdominal pain in DBE patients. Furthermore, we want to investigate if CO2 insufflation facilities a deeper intubation of the endoscope and thus a more complete examination of the small bowel mucosa.~Hypothesis~The use of CO2 in DBE leads to a reduction in abdominal pain for the patient when compared with the use of air.~The use of CO2 in DBE leads to deeper intubation when compared to air insufflation.~Methods Study design The study is designed as a two-centre randomised controlled trial. The participating centres are Rikshospitalet University Hospital, Oslo, Norway and University Hospital Muenster, Germany.~Randomisation to the two treatment groups (CO2 or air insufflation) is performed on basis of the individual participant. Equally large groups are randomised, using block randomisation (blocks of six patients) for each of the participating centres. Randomisation (using SPSS statistical software package) is performed by an independent researcher, who is not part of the DBE team.~Individuals eligible for inclusion are patients referred for DBE at the trial centres who do not fulfil one of the following exclusion criteria:~Age under 16 years~Inability to understand information for participation~Refusal of participation~All eligible individuals are informed about the nature of the study. All individuals provide written informed consent before entering the trial. Patients who do not wish to participate in the present trial are treated according to standard procedures (using air insufflation).~All procedures are performed by experienced endoscopists. Both patients and endoscopists are blinded with regard to type of gas used for any particular patient.~Sedation is performed according to current standards at the centres.~Double-balloon procedure DBE is performed using the DBE endoscope system (Fujinon Inc, Japan), as described in the literature (1-4). The DBE endoscope consist of a 200-cm long video endoscope with an outer diameter of 8.5 mm and a flexible overtube with a length of 145 cm and an outer diameter of 12 mm. Latex balloons are attached to both the endoscope and the overtube. These balloons are inflated and deflated during insertion, as described elsewhere in detail (1,2).~Gas insufflation CO2 is insufflated using Fujinons equipment (or other, to be specified) Air is insufflated using the ordinary air inlet system of the endoscope rack. The air inlet button is hidden from the view of the endoscopist to prevent unblinding (technical details to be specified in cooperation with company).~Evaluation of pain and discomfort A questionnaire is used to classify patient pain during and after the procedure. Visual analogue scales (100-mm) are used to quantify abdominal pain during the examination and at 1, 3, 6, and 24 hours after the procedure, as validated in recent studies (7,8). The questionnaire is given to every participant after the procedure, to be filled in the next day, and mailed back to the respective trial centre using prepaid envelopes.~Evaluation of ERCP examination parameters All procedure parameters of interest (e.g. duration, depth of insertion, use of sedatives) are registered by the endoscopist immediately after the examination using the existing GI lab databases.~Ethics The regional ethics committees of the participating centres will be asked for approval of the study protocol.~Power analysis A 15% reduction in mean pain score on VAS is considered to be clinically important to detect. There are no studies available regarding this outcome in DBE. Therefore, pilot study will be performed with 20 included patients in every group (air/CO2). The results of the pilot study will estimate the standard deviation needed to calculate power and thus size of the study.~Ownership Data are owned by the respective centres. Publication of the study results is planned in a peer-reviewed journal. Michael Bretthauer and Dirk Domagk will co-ordinate study design, data generation and analysis and a first manuscript draft. Michael Bretthauer and Dirk Domagk will be the first authors of the planned publication, the other members of the study groups will be co-authors.~Budget All procedures in the present study are performed in ordinary patients, with ordinary staff and endoscopists. Therefore, no extra costs occur for personal. For the purpose of the present study, however, some technical equipment has to be purchased (to be specified).~Financial funding is needed for meetings of the study group and prepaid envelopes.~References~Yamamoto, Sekine Y, Saito Y, et al. Total enteroscopy with a non-surgical steerable double-balloon method. Gatrointest Endosc 2001;53:216-20~May A, Nachbar L, Wardak A, et al. Double-balloon enteroscopy: preliminary experience in patients with obscure gastrointestinal bleeding or chronic abdominal pain. Endoscopy 2003;35:985-91~May A, Nachbar L, Ell C. Double-balloon enteroscopy (push-and-pull enteroscopy) of the small bowel: feasibility and diagnostic and therapeutic yield in patients with suspected small bowel disease. Gastrointest Endoc 2005;62:62-70~Ell C, May A, Nachbar L, et al. Push-and pull enteroscopy in the small bowel using the double-balloon technique: results of a prospective European multicenter study. Endoscopy 2005;37:613-6~Hussein AMJ. Carbon dioxide insufflation for more comfortable colonoscopy. Gastrointest Endosc 1984; 30:68-70~Stevensen GW et al. Pain following colonoscopy: elimination with carbon dioxide. Gastrointet Endosc 1992;38:564-567~Bretthauer M, Thiis-Evensen E, Hoff G, et al. A randomized controlled trial to assess the safety and efficacy of carbon dioxide insufflation in colonoscopy. Gut 2002; 50:604-607~Bretthauer M, Hoff G, Thiis-Evensen E, et al. Carbon dioxide insufflation reduces discomfort due to flexible sigmoidoscopy in colorectal cancer screening. Scand J Gastroenterol 2002, 37:1103-8~Sumanac K, Zealley I, Fox B , et al. Minimizing postcolonoscopy abdominal pain by using CO2 insufflation: a prospective, randomized, double blind, controlled trial evaluating a new commercially available CO2 delivery system. Gastrointest Endosc 2002;56:190-4~Information and consent Research study: Insuflation of carbon dioxide(CO2) in double balloon enteroscopy~Dear patient~You are hereby kindly invited to participate in a research study while undergoing your planned endoscopic investigation of the small bowel (DBE, double balloon enteroscopy)~During this examination, it is common practice to insufflate gas into the small bowel to provide the examiner with an adequate view. At the vast majority of hospitals around the world, ordinary room air is used for insufflation. However, the insufflated air can produce pain and abdominal discomfort for patients during and in the hours after the examination.~There is some evidence that the use of carbon dioxide gas (CO2) instead of air can reduce abdominal pain after examination. In this study, we would like to find out if this is true.~Study participants will be divided by random into a group that receives CO2 during the DBE examination and one group that receives air.~Both the endoscopist and you as a patient do not know which gas is being used. Only the endoscopy assistant knows the type of gas used during your examination. After the examination, you will receive a short questionnaire about any complaints or discomfort, which we would like to ask you to fill in at home and mail back to the hospital.~If you decide not to participate in the study, your examination will be performed with the use of air insufflation (standard method).~The present study has been approved by the ethics committee. All information will be treated strictly confidential and only for research purposes within this study. Participation is free of charge and not mandatory. You may decline your participation at any time.~Yours sincerely~Dr. med. Michael Bretthauer (tlf:)~Written informed consent I hereby declare my participation in the abovementioned research study. I am aware of that participation is voluntary.~Date Signature~Vedlegg C~Carbon dioxide versus air insufflation in double-balloon endoscopy~Patient questionnaire (Version 300606), Michael Bretthauer~This questionnaire is to be filled in the day after the procedure and to be mailed back to the GI lab.~Patient ID~Was the examination any painful??~Please score the degree of pain with a vertical dash on the scale below, between No pain (left margin) and very heavy pain (right margin).~No pain Very heavy pain~Did you have any abdominal pain or distension after the examination?~Please score the degree of pain with a vertical dash on the scale below, between No pain (left margin) and very heavy pain (right margin).~No pain Very heavy pain~1 hour after the exam~3 hours after the exam~6 hours after the exam~24 hours after the exam~Please use the back of the questionnaire for any comments

Double-balloon enteroscopy (DBE) is a novel endoscopic procedure for visualising the entire small bowel. In any GI endoscopy procedure it is mandatory to insufflate gas into the bowel to secure good visualisation. All endoscopes used for GI endoscopy provide a gas insufflation unit. Currently, air is used for this purpose in more than 90% of centres throughout the world. The use of air, however, is far from ideal to use for insufflation in GI endoscopy. After GI endoscopy, significant amounts of air are usually retained in the bowel segment inspected (5). This air has to pass the GI tract and exit physiologically through the rectum. Thus, abdominal pain and discomfort during and after the examination due to the retention of air has been shown to be very common during and after endoscopic procedures (5-9).~Carbon dioxide gas (CO2), unlike air, is rapidly absorbed from the bowel. Within minutes, several litres of CO2 can be absorbed from the GI tract. The use of CO2 has been shown to result in more comfortable examinations in both colonoscopy and flexible sigmoidoscopy in several randomised trials (6-9). In these studies, CO2 insufflation almost completely reduced procedure-related pain and discomfort.~To our knowledge, no research has been performed investigating the use of CO2 in DBE. DBE is a long-lasting procedure (mean examination time 75 minutes (4)). Large volumes of air are insufflated during the procedure, leading to significant distension of the small bowel during and after the examination.~One of the main technical difficulties in DBE is the formation of small bowel loops and scarp angels during deep intubation of the endoscope. These loops and angels are the major restriction to deep intubation of the endoscope. Loops and scarp angels are more pronounced in air-distended bowel segments.~The aim of the present study is to examine whether CO2 insufflation leads to a reduction of abdominal pain in DBE patients. Furthermore, we want to investigate if CO2 insufflation facilities a deeper intubation of the endoscope and thus a more complete examination of the small bowel mucosa.~The study is designed as a two-centre randomised controlled trial. Randomisation to the two treatment groups (CO2 or air insufflation) is performed on basis of the individual participant.

There is no data regarding success rates and incidence of carotid punctures during central venous cannulation (CVC) in pregnant patients. We hypothesize that because of the anatomical and physiological changes associated with pregnancy, these patients are at higher risk of procedure failure and carotid puncture than the general population. The purpose of our study is to determine the success rate and incidence of carotid punctures using an ultrasound-simulated procedure in pregnant and non-pregnant patients.~Pregnant patients and adult female volunteers (controls) were recruited. Subjects were placed supine with wedge under the right hip, and head turned 35 degrees to the left. Two different approaches for CVC, the central landmark and the palpatory approach were used. The ease of identification of the landmarks was noted. CVC was simulated using an ultrasound probe, on pre-marked points. Ultrasound images were obtained, within the same parasagittal plane, directed 30 degrees caudad, in a manner simulating how a syringe and needle would be placed for central venous cannulation. The investigator placing the probe was blinded to the image being generated. The vertical cursor of the ultrasound, which serves to delineate the path of a needle, was placed in the image. If the cursor intersects the vein, the attempt is considered successful. If the first attempt is not successful, the investigator placing the probe was asked to redirect the probe to the second and if necessary to the third marked point. This was done for each approach. If the cursor intersects the carotid artery, the attempt is considered an accident and no further attempts were made. In addition to determining the success rate and the incidence of carotid punctures, the relative position of vein and artery was studied in each patient. For each approach, the best image was recorded, and three experienced anesthesiologist scored the images for vein and artery degree of overlapping.

There is no data regarding success rates and incidence of carotid punctures during central venous cannulation (CVC) in the pregnant patients. We hypothesize that because of the anatomical and physiological changes associated with pregnancy, these patients are at higher risk of procedure failure and carotid puncture than the general population. The purpose of our study is to determine the success rate and incidence of carotid punctures using an ultrasound-simulated procedure in pregnant and non-pregnant patients.

Many adolescents in the U.S., even very young adolescents, are engaging in sexual risk behaviors that put them at risk for sexually transmitted diseases (STDs) and unintended pregnancy. Studies show that parents can play a significant role in promoting healthy sexual development and risk reduction among adolescents. Parenting approaches such as engaging in open and responsive communication, providing appropriate levels of supervision, and keeping involved in children's lives are associated with better adolescent outcomes. However, many parents are uncertain about how to talk with their adolescents about sex. Worksites provide an untapped but promising setting in which to reach parents to help them develop parenting and communication skills.~The UCLA/RAND Center for Adolescent Health Promotion has developed a worksite-based parenting program for parents of adolescents (grades 6-10) to improve parent-adolescent communication and reduce adolescent sexual risk behaviors. Specifically, the Center has developed Talking Parents, Healthy Teens for parents with adolescent children to teach communication skills as well as basic facts about sex and other important adolescent issues. The program aims to help parents understand adolescent development and the changes in adolescents' thoughts and feelings about sexual issues and other risk behaviors. It helps parents develop skills for discussing sensitive but important topics with their adolescents, and for teaching their adolescents decision-making and problem-solving skills. The program also emphasizes the importance of parents knowing what is going on in their adolescents' lives (often called parental monitoring). Although parents feel a need for help on such issues, they often tend to be too busy to attend ongoing programs. Therefore, we bring the program to them at their worksite. The program involves groups of about 12-15 parents who meet for an hour at lunch-time once a week for eight consecutive weeks. We serve a free lunch during the sessions.~We are evaluating the effectiveness of the Talking Parents, Healthy Teens program primarily with confidential surveys of the participants before and after the program. We also ask participants' adolescents (who are not in the parenting program) to fill out surveys as well. Among parents who initially express interest in the program, we randomize parents after they complete their baseline survey into an intervention group that takes the parenting program and a control group that does not. Both of these groups fill out confidential surveys over the course of several years. After the study has been conducted at a number of worksites, the research team will statistically compare survey answers for the two groups to see how well the program works. The results of the evaluation will be submitted for publication in academic journals.

Many adolescents in the U.S., even very young adolescents, are engaging in sexual risk behaviors that put them at risk for sexually transmitted diseases (STDs) and unintended pregnancy. Studies show that parents can play a significant role in promoting healthy sexual development and risk reduction among adolescents. The UCLA/RAND Center for Adolescent Health Promotion has developed Talking Parents, Healthy Teens, a worksite-based parenting program for parents of adolescents (grades 6-10) to improve parent-adolescent communication and reduce adolescent sexual risk behaviors. We are evaluating the effectiveness of the program primarily with confidential surveys of the participants before and after the program.

Administration of bronchodilator drugs with metered-dose inhalers (MDIs) is difficult for some patients because the timing of the spray and the inhalation must be coordinated exactly. Use of spacers seems to improve delivery in these patients. It is not clear, however, if there is any advantage to a spacer for patients who are able to use an MDI with correct technique.~The purpose of the present study is to determine whether use of a small volume spacer is associated with better bronchodilatation in an unselected population of patients with documented reversible airflow limitations. The intervention in the first part of the study is use of an MDI with or without a spacer to deliver a bronchodilator (2 puffs, 0.4 mg of fenoterol). Spirometry is performed before and after the inhalation.~The second part of the study is conducted identically to the first with the same conditions and variables but with the addition of rinsing the mouth with 100 mL of water after inhaling the bronchodilator but before the second spirometry measurement.~The outcome to be measured is the increase in forced expiratory volume in 1 second (FEV1) and forced expiratory flow rate (FEF25-75%).

The purpose of the present study is to determine whether use of a small volume spacer is associated with better bronchodilatation in an unselected population of patients with documented reversible airflow limitations.

Fetal head engagement measured by ultrasound as a predictive factor of labor outcome in women with induced labor~T. EGGEBØ, L. K. GJESSING, I. ØKLAND, C. HEIEN, P. ROMUNDSTAD*, K. Å. SALVESEN** Department of Obstetrics and Gynaecology, Stavanger University Hospital, Norway * Department of Public Health, NTNU, Norway, St Olavs Hospital, Trondheim University Hospital~** National Center for Fetal Medicine, Department of Obstetrics and Gynaecology, Trondheim University Hospital (St. Olav's Hospital) and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology~KEYWORDS:~Ultrasound, induced labor, cervical length, engagement of fetal head, occiput posterior, Bishop score, outcome of labor~Objective The aim of the study is to evaluate any possible associations between engagement of the fetal head, the cervical status or occiput posterior position and the outcome of labor in women with induced labor, and to compare the value of ultrasound measurements with Bishop score in predicting operative deliveries.~Methods The ultrasound examinations will be carried out in 275 women immediately before induction of labor. A transabdominal scan will be performed to determine the position of the fetal occiput, a transperineal scan with transverse view to determine the degree of engagement and a transvaginal examination to evaluate the cervical length and the cervical angle.. The Bishop score will be performed by another examinator who is blinded to the results of the ultrasound examinations. The time from induction to delivery will be tested in a Cox regression analysis with fetal head engagement, cervical length and parity as possible predictive factors and maternal age, BMI, gestational age, birth weight and head circumference as possible confounders.~Inclusion and exclusion criteria:~Women were eligible for the study if they had a live singleton pregnancy with cephalic presentation and a gestational age of more than 37 completed pregnancy weeks according to a mid-trimester scan.~Statistical analysis Appropriate statistical tests for comparisons, such as Mann Whitney U test, chi-square test, Fisher's exact test, Pearson correlation, Kaplan Meier survival analysis and Cox regression analysis will be used. For receiver-operating characteristics (ROC) curves, the area under the curve will be used as discriminator. P-values < 0.05 will be considered significant.

The aim of the study was to evaluate any possible associations between engagement and position of the fetal head and the outcome of labor in women with induced labor, and to compare the value of ultrasound measurements in predicting the time from induction to delivery and operative deliveries.

Nutritional deficiencies are a major problem in school children in India and have a variety of adverse effects on their cognitive development and growth, and increase susceptibility to infections. There is strong evidence for beneficial effects of iodine, iron and protein-energy on cognitive development in children, while evidence for vitamin B6, vitamin B12, folate, zinc and, omega-3 fatty acids and in particular docosahexanoic acid (DHA) is limited and inconclusive. The present study will investigate the efficacy of foods fortified with omega-3 fatty acids including DHA and a micronutrient mix (iodine, iron, vitamin B2, vitamin B6, vitamin B12, folate, zinc, calcium, vitamin A, vitamin C and vitamin E) on improving cognitive development and performance in school children in India.~The study will follow a randomised, double-blind, placebo-controlled 2x2 factorial design in which children aged 7-9 years will be randomised to one of four treatment groups and prospectively followed for a period of twelve months to assess cognitive development and performance and other selected outcome variables such as growth, morbidity and immune response. Intervention will take place in primary schools, where children will receive three intervention products daily. The products will contain omega-3 fatty acids with micronutrients, or micronutrients only, or omega3 fatty acids only or a placebo. At baseline, 6 and 12 months cognitive tests will be administered and blood samples will be drawn to assess nutritional status and immune response to hepatitis B vaccination. Compliance will be measured daily and morbidity will be monitored weekly by means of a questionnaire. Anthropometric measurements will be carried out monthly.~It is expected that, after 12 months of intervention, children consuming products containing omega-3 fatty acids with micronutrients will have statistically significant higher scores and higher improvement in scores on cognitive tests, will grow taller and have a better immune response than children consuming control products.

Nutritional deficiencies are a major problem in school children in India and have a variety of adverse effects on their cognitive development and growth, and increase susceptibility to infections. There is strong evidence for beneficial effects of iodine, iron and protein-energy on cognitive development in children, while evidence for vitamin B6, vitamin B12, folate, zinc and, omega-3 fatty acids and in particular docosahexanoic acid (DHA) is limited and inconclusive. A randomised, double-blind, placebo-controlled 2x2 factorial design will be conducted to assess the effect of a micronutrient with or without omega-3 fatty acids on cognitive development and performance and other selected outcome variables such as growth, morbidity and immune response in children of 7-9 years of age in India.

Following a meal, gut-produced incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the circulation. GLP-1 and GIP, the two dominant incretin hormones, are part of a natural endogenous system involved in maintaining glucose homeostasis. In the presence of normal or elevated, but not low, glucose concentration, both GLP-1 and GIP increase insulin secretion from pancreatic islet beta-cells. GLP-1 also lowers glucagon secretion from pancreatic alpha-cells and delays nutrient delivery from the stomach by inhibiting gastric emptying. These combined effects improve glucose tolerance providing the rationale for a therapeutic potential of GLP-1 analogues in the treatment of diabetes mellitus.~A dominant gastrointestinal action of synthetic GLP-1 is the inhibition of gastroduodenal and stimulation of pyloric motility, resulting in a delay of gastric emptying and in decreased glycemic excursions. Postprandial glucose fluctuations have been demonstrated to be an important determinant of glycemic control as assessed by A1C. Moreover, emerging evidence shows a strong link between transient postprandial hyperglycemia and microvascular and macrovascular complications in diabetes mellitus. Deceleration of gastric emptying is now considered as mechanism to lower postprandial glycemia in patients with diabetes mellitus. It is part of the pharmacodynamic profile of new antidiabetic incretinomimetica. In contrast, inhibition of the enzyme dipeptidylpeptidase 4 (DPP-4) which is responsible for the rapid degradation of GLP-1 failed to show an effect on gastric emptying in human although plasma GLP-1 was increased by twofold. Most of our understanding of the effects of GLP-1 is based upon studies employing synthetic GLP-1 whereas only little is known about endogenously released GLP-1.~Using the specific GLP-1 receptor antagonist exendin(9-39) we were able to show that endogenous GLP-1 acts as an incretin hormone in human. Moreover, the inhibition of antroduodenal and the stimulation of pyloric motility during a duodenal glucose load were reversed by the GLP-1 receptor antagonist. In order to more completely evaluate the effects of GLP-1 as an enterogastrone, the present study examines the effects of exendin(9-39) on antropyloroduodenal and proximal gastric motility during a physiological meal. As cholinergic pathways are thought to be involved in inhibitory actions of GLP-1 we combine the GLP-1 receptor antagonist with the muscarinergic antagonist atropine. To ensure a comparable stimulation of GLP-1 under all experimental conditions we decide to perfuse the meal directly into the duodenum.~Comparisons: In ten healthy volunteers, an interdigestive period is followed by 70 min with duodenal perfusion of a mixed liquid meal (250 kcal). On four days and in random order, exendin(9-39) (300 pmol•kg-1•min-1), atropine (5 µg•kg-1•h-1), exendin(9-39) + atropine or saline are intravenously infused. Antro-pyloro-duodenal perfusion manometry and fundic motility (electronic barostat) are assessed in parallel. Isobaric distensions of the proximal stomach were performed determining compliance.

The purpose of this study in humans is to define the effects of the endogenous hormone GLP-1 on gastroduodenal motility and on endocrine pancreatic secretion by using the specific GLP-1 receptor antagonist exendin(9-39). To elucidate possible cholinergic pathways, we combined exendin(9-39) with the muscarinergic antagonist atropine.

Cardiopulmonary bypass (CPB) is associated with fluid overload and edema formation occasionally resulting in vital organ dysfunction affecting heart, respiratory system , gastrointestinal tract and brain. Hyperosmolar/hyperoncotic preparations (HSH/HSD) have been used in cardiac surgery essentially with the aim to mobilize fluid excess and improve postoperative cardiorespiratory function.Most studies dealing with the administration of HSD or HSH during and after CPB, have used protocols recommended for treatment of severe hypovolemia and shock, that is 4 mL/kg as a bolus, given within minutes.In animal experiments we have used HSD or HSH, 1 mL/kg/h to a total dose of 4 mL/kg during CPB. The use of HSH/HSD reduced the total fluid gain about 50 % and resulted in significantly lower content of tissue water in vital organs as heart and lungs. In the actual clinical trial we hypothesize that a continuous infusion of HSH will reduce fluid load and increase hemodynamic and respiratory functions monitored with the PiCCO system in patients undergoing coronary artery bypass with CPB.

Cardiopulmonary bypass(CPB) is associated with increased fluid extravasation and edema formation. A continuous infusion of a mixture of hypertonic saline/hydroxyethyl starch (HSH)during CPB reduced fluid extravasation and total fluid gain during bypass in an animal model. We hypothesize that a continuous infusion of HSH will reduce fluid load and increase hemodynamic and respiratory functions in patients undergoing coronary artery bypass with CPB.

Venepuncture is a painful procedure commonly performed in premature infants. Nonpharmacological intervention (oral sucrose solution) can reduce neonatal pain. EMLA cream is an oil in water emulsion of an eutectic mixture of prilocaine and lignocaine; it is an local anesthetic cream. Very few reports have looked at the efficacy of EMLA in preterm infants.~This randomized bicentric trial will investigate the efficacy of topical EMLA cream with oral sucrose solution compared to oral sucrose solution alone before venepuncture in preterm infants.

This randomized bicentric trial will investigate the efficacy of topical EMLA cream with oral sucrose solution compared to oral sucrose solution alone before venepuncture in preterm infants.

OBJECTIVES:~Primary~Compare the effect of acetylsalicylic acid (aspirin) vs placebo on mammographic density in healthy postmenopausal women with a moderate or high level of breast density.~Secondary~Determine whether there is a differential response in mammogram density to aspirin treatments in individual homozygous wild-type, heterozygous, and homozygous variant for several UGT gene polymorphisms.~Determine the effect of aspirin therapy on potential adverse events, including gastrointestinal symptoms and signs, bleeding events, blood pressure, and other major comorbidities and hospitalizations, as well as generalized symptoms, in these participants.~Determine the effects of aspirin therapy on putative biomarkers of breast and ovarian cancer that are currently being validated as part of ongoing Fred Hutchinson Cancer Research Center Ovarian SPORE activities.~Determine the effects of aspirin therapy on levels of serum estradiol, estrone and sex hormone binding globulin (SHBG) as measured by radioimmunoassay at baseline and 6 month timepoints~OUTLINE: This is a randomized, placebo-controlled, double-blind study. Participants are randomized to 1 of 2 treatment arms.~Arm I: Participants receive oral acetylsalicylic acid (aspirin) daily for 6 months.~Arm II: Participants receive oral placebo daily for 6 months. In both arms, participants undergo a repeat mammogram at 6 months.~Blood and urine samples are collected at baseline and at 6 months. Single-nucleotide polymorphisms in the UGT genes and variable number of tandem repeat-type polymorphisms are genotyped.~PROJECTED ACCRUAL: A total of 144 participants will be accrued for this study.

RATIONALE: Aspirin may be effective in reducing breast density in healthy postmenopausal women with a moderate or high level of breast density.~PURPOSE: This randomized clinical trial is studying the effect of aspirin on mammogram density compared with a placebo in healthy postmenopausal women with a moderate or high level of breast density.

Conventional hemodialysis requires transient systemic anticoagulation to prevent blot clotting after contact with the extracorporeal circuit. However, low molecular weight heparin (LMWH) or unfractioned heparin are contra-indicated in dialysis patients at risk for hemorrhagic complications. In this setting, several procedures theoretically allow dialysis without systemic heparinization, but randomized studies to compare them are lacking. The gold standard is the use of iterative rises of the extra corporeal circuit with isotonic saline ( rises ). Two emerging procedures are increasingly used : continuous pre-dilution of the arterial line ( pre-dilution ) and the use of a specific dialysis membrane (NEPHRAL 400 ST) coated with heparin immediately before use ( heparin adsorption ).~We propose a monocentric prospective randomized open study to compare rises , pre-dilution and heparin adsorption in chronic hemodialysis patients with contra-indication to the use of LMWH. Main criteria will be extra-corporeal circuit clotting, with dialysis efficiency and tolerance as secondary criteria. Comparison will be made on grounds of n-of-1 trial, i.e. series of randomized cross-over tests in individuals. We have planned to include 75 patients in this study, with 1050 LMWH-free dialysis sessions.~We hope to demonstrate chat by comparison wit rises, pre-dilution and heparin absorption techniques reduce the rate of extra-corporeal circuit by 30 and 50% respectively. We also hope to show that heparin adsorption (i) better preserves membrane integrity throughout the dialysis session, resulting in enhanced dialysis efficiency ; (ii) avoids extra fluid infusion and ultrafiltration, resulting in better dry weigh achievement and better clinical tolerance.

Conventional hemodialysis requires transient systemic anticoagulation to prevent blot clotting after contact with the extracorporeal circuit. However, low molecular weight heparin (LMWH) or unfractioned heparin are contra-indicated in dialysis patients at risk for hemorrhagic complications. In this setting, several procedures theoretically allow dialysis without systemic heparinization, but randomized studies to compare them are lacking. The gold standard is the use of iterative rises of the extra corporeal circuit with isotonic saline ( rises ). Two emerging procedures are increasingly used : continuous pre-dilution of the arterial line ( pre-dilution ) and the use of a specific dialysis membrane (NEPHRAL 400 ST) coated with heparin immediately before use ( heparin adsorption ).

The glycemic index (GI) is a ranking of carbohydrate containing foods according to the rate at which they raise blood glucose levels after eating. A recent meta-analysis of randomized clinical trials (RCT) suggests that choosing low GI foods has a small but clinically useful effect on medium-term glycemic control in patients with type 2 diabetes. However, in most of the reviewed RCTs, patients were fed experimental diets and therefore there is still controversy over the applicability of GI in the clinical setting for management of diabetes. In addition, there is no evidence that long-term consumption of a low GI diet will contribute to improved glycemic control in people with diabetes.~Our ultimate goal for a future larger RCT is to evaluate the long-term effects of using low GI diet in type 2 diabetics. The primary outcome variable of the future large trial will be glycosylated hemoglobin levels (HbA1c), a measure reflecting average glycemic level during the preceding 2-3 months. The proposed feasibility study will recruit 40 patients with type 2 diabetes and will randomly assign them to one of two groups: a low GI nutrition education group (low GI group) and a standard ADA dietary education group as the control group (ADA group) (20 patients in each group).~For both groups, the intervention phase will last 6 months and consist of an initial group session, an individual session, and then four group counseling sessions. The follow-up phase will be six months and consist of two group booster sessions, one at 8-months and another at 10-months. The low GI nutritional education will be primarily targeted at a low GI diet. The focus is not on decreasing total carbohydrate intake, but rather encouraging patients to substitute low GI foods for high GI foods. The dietary intervention will be based on a patient-centered counseling model which has been demonstrated to facilitate health behavior change. Data collection points coincide with two phases of the intervention. Assessments, including demographics, anthropometric measurements, diet and physical activity recalls, and clinical data, will be conducted at baseline, and at 6 and 12 months after randomization, with blood samples collected at each interval. We will track response to recruitment, adherence, and retention. Quantitative and qualitative methods will be used to assess acceptability of the intervention.~The aim of this proposed 2-year study is to gather pilot data on the feasibility of implementing a nutritionist-delivered low GI intervention to reduce dietary GI in patients with type 2 diabetes. Our outcomes are recruitment and retention rates, as well as physiological measures (HbA1c, blood pressure, and body mass index), dietary GI scores and acceptability of the intervention.~By improving glycemic control, many of the devastating complications of diabetes are to a large extent preventable. The use of a low GI diet to improve glycemic control is relatively new and untested. However, a low GI diet may be a cost-effective approach to preventing diabetes-related complications. Testing the feasibility of such a program and its potential impact would be an important step towards an RO1 application to the NIH.

By improving glycemic control, many of the devastating complications of diabetes are to a large extent preventable. The use of a low GI (glycemic index) diet to improve glycemic control is relatively new and untested. However, a low GI diet may be a cost-effective approach to preventing diabetes-related complications. The aim of this proposed 2-year study is to gather pilot data on the feasibility of implementing a nutritionist-delivered low GI intervention, to reduce dietary GI in patients with type 2 diabetes, and to compare it with a nutritionist-delivered standard American Diabetes Association (ADA) diet intervention. Our outcomes are recruitment and retention rates, as well as physiological measures (HbA1c, blood lipids, blood pressure, and body mass index), dietary GI scores and acceptability of the intervention.~Primary hypotheses:~1. Recruitment and retention rates for the low GI intervention will be satisfactory.~Secondary hypotheses:~Participants in the low GI intervention group will show more favorable changes in physiological measures than participants in the ADA diet group.~Participants in the low GI group will be successful in lowering the GI of their diet.~Participants will find the intervention acceptable.

This study is an open-label, three-treatment, six sequence, three-period, single center crossover study to evaluate the pharmacokinetics of intravenous diclofenac sodium DIC075V (18.75 mg and 37.5 mg) versus oral diclofenac potassium (Cataflam® 50 mg) in healthy adult volunteers following single- and multiple-dose administration. Each treatment sequence received 1 dose every 6 hours (for a total of 4 doses per treatment sequence) with a 48-hour washout period between treatment sequences.

The purpose of this study is to assess the pharmacokinetic parameters of intravenous diclofenac sodium (DIC075V) 18.75 mg and 37.5 mg following single- and multiple-dose administration, as compared to oral diclofenac potassium (Cataflam® 50 mg), the approved reference product.

Uric acid plays a role not only in the pathogenesis of gout but is also a predictor of cardiovascular disease, hypertension and renal disease in man. We have identified the human urate ion channel transporter (hUAT), located in the proximal convoluted tubule of the kidney that is involved in both the secretion and reabsorption of urate across the tubule. This channel has a unique lectin binding site that in in-vitro studies, has been found to be modulated by glucose, galactose and lactose. We have also identified a mutation (G/A polymorphism) in our laboratory, that in in-vitro studies has demonstrated diminished hUAT channel activity. Cross-sectional studies have earlier shown that uric acid levels vary with serum glucose levels. Studies have also reported that a low-fat dairy diet reduces the incidence of gout, while others have shown that this diet reduces blood pressure significantly when compared with a non-dairy diet. We hypothesize that the effect of blood glucose levels in lowering uric acid levels is through the regulation of hUAT channel activity. We also hypothesize that a low-fat dairy diet reduces serum uric acid levels through hUAT regulation leading to a decrease in the incidence of gout and a reduction in blood pressure levels. In our proposed randomized, controlled, cross-over trial in healthy adult volunteers, we aim to study the effect of a low-fat dairy diet and a non-dairy diet on serum uric acid levels, the renal fractional excretion of uric acid and blood pressure. We will also study the effect of an acute intravenous infusion of glucose on these parameters. DNA analysis for hUAT mutations of study subjects will be done to assess if there is a blunted response of hUAT activity in subjects with the polymorphism as compared to normal individuals.

The purpose of the study is to determine whether low fat dairy diet reduces serum uric acid levels.

The problem-solving approach is found in virtual patient designs concerned with teaching clinical reasoning and diagnosis. Generally the student has to collect a range of information, usually from menus of possible history questions, physical examination, and lab tests, and make diagnostic and therapeutic decisions based on their findings. The information is not cued - the student have to decide what is relevant. An introduction screen is shown to the student when the virtual patient is initiated. Case author have used it differently - some entered a complete chief complaint and part of anamnesis findings while other have not disclosed anything about the patient. There is a lack of evidence of the impact of the information provided in the introduction screen on the students diagnostic and therapeutic decisions. The reasoning pattern may also be altered if positive findings are provided to the student without an active request for it.~The results will be of importance when virtual patients are used for assessing students.

There is a lack of evidence of the impact of the information provided in the introduction screen on the students diagnostic and therapeutic decisions. The reasoning pattern may also be altered if positive findings are provided to the student without an active request for it.~The results will be of importance when virtual patients are used for assessing students.

The United States (US) has the highest unintended pregnancy rate of any developed country. Of the 6.4 million pregnancies in the US each year, almost half are unintended (49%). Roughly half of these (22% of all pregnancies) result in unintended births, while 20% of all pregnancies result in abortion. Postpartum women are particularly susceptible, with an unintended pregnancy rate of 10%-44% in the first year postpartum. These unintended pregnancies occur despite the recommendation that a contraceptive method be selected prior to hospital discharge.~Given the high rate of unintended pregnancy in the United States, particularly in postpartum women, there is a need for reliable, effective, long-term contraception such as the IUD in postpartum women. Postplacental insertion of intrauterine contraception would help to address this need. The IUD is a highly effective but underused method of postpartum contraception. Although the expulsion rate in postplacental insertion is higher than interval insertion, the benefits of highly effective contraception available immediately after delivery may outweigh the risks of expulsion.~To date, there have been no randomized trials of postplacental insertion of the LNG-IUD in the United States. One pilot study in the United States of 20 subjects who received an ultrasound-guided postplacental insertion of the LNG-IUD showed an acceptable expulsion rate of 10% and no infections over a 10-week follow-up, thus making postplacental insertion of LNG-IUD safe for further study.~This study is a randomized controlled trial comparing 6 month usage rates of the levonorgestrel-releasing intrauterine device (LNG-IUD) when inserted postplacentally after vaginal delivery or delayed placement at 6-8 weeks postpartum. One hundred sixty-eight women receiving prenatal care at Magee-Womens Hospital, Pittsburgh, PA, who are interested in using the LNG-IUD for contraception will be enrolled during their pregnancy. The IUD will be inserted within 10 minutes after delivery of the placenta in women randomized to immediate insertion. Delayed IUD insertion will be performed at the first postpartum visit in 6-8 weeks. All subjects will follow up in person at 6-8 weeks and 6 months after delivery. A telephone interview will occur at 3 months after delivery for all subjects.~Subjects who are not eligible for insertion due to post-randomization ineligibility criteria will be referred to their primary gynecologist or midwife for delayed IUD placement. They will be contacted by phone at 3 and 6 months to assess quality of life, contraceptive usage, and unintended pregnancy rates.

This study is a randomized controlled trial comparing 6 month usage rates of the levonorgestrel-releasing intrauterine device (LNG-IUD) when inserted postplacentally after vaginal delivery or delayed placement at 6-8 weeks postpartum. Given the high rate of unintended pregnancy in the United States, particularly in postpartum women, there is a need for reliable, effective, long-term contraception such as the IUD in postpartum women. Postplacental insertion of intrauterine contraception would help to address this need. The primary hypothesis of this study is that use of the LNG-IUD at 6 months after vaginal delivery will be higher in women who have immediate postplacental insertion as compared to delayed insertion 6-8 weeks following delivery.

For this study, you will be asked to complete a personal interview. During the interview, you will be asked questions about your demographics (age, sex, etc.), certain environmental exposures, your medical history, family history, your diet, and your smoking and alcohol use histories. It should take around 50 minutes to complete the interview.~You will also have around 2 ½ tablespoons of blood drawn for special tests. These tests will look for any biologic factors associated with certain cancers. The interview and blood draw will be scheduled at the time and place of your convenience. You will not be informed of the results of any of the testing done with your samples.~There is a possibility that you might be contacted in the future about if researchers need clarification on any of information already collected. You are free to refuse any further participation if you wish.~This is an investigational study. Up to 1,500 participants will take part in this study.

The goal of this research study is to identify biologic and lifestyle factors that may increase a person's risk of developing certain types of cancer.

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. Many people suffer from this disease for years and die prematurely from it or its complications. COPD is the fourth leading cause of death in the world, and further increases in its prevalence and mortality can be predicted in the coming decades. COPD is characterized by a slowly progressing, irreversible airflow limitation caused by chronic inflammation in the bronchioles. It is diagnosed by performing spirometry. In the early stages, COPD can be asymptomatic, although episodes of coughing, often with sputum production, are not rare. In more advance stages, when there are also symptoms of shortness breath on exertion, a significant part of lung function may be reduced. The diagnosis of COPD is usually established in the later stages, and this diagnostic delay may either be due to the patient's gradual adaptation to a decreasing lung function or denial of the disease. In addition, because doctors are unaware of, or not responding to the symptoms of the patient. The main cause of COPD is smoking and it often manifests itself after someone has been smoking more than 20 cigarettes a day over 20 years (20 pack years). A smoker who is sensitive to cigarette smoke may therefore have spirometric changes between the ages of 40 to 45 years if they started smoking as a teenager or early 20th. It has been estimated that 15-20% of smokers develop COPD, but more recent research suggests that as many as 50% develop COPD if the smoker reaches a high age.~Treatment of COPD patients depends on the stage of the disease. First of all it is strongly recommended quit smoking, then bronchodilators drugs are added. In more advanced stages in inhaled corticosteroids and pulmonary rehabilitation are added. In hypoxemic patients a long term supplemental oxygen is advised.~The addition of sputum modifiers drugs is equivocal, since no objective improvement was documented.~N-Acetylcystein (NAC) is a drug known for its anti-oxidant and mucolytic activity. In animal models of disease it showed its beneficial activity , whereas in human such changes weren't demonstrated. In all the studies FEV1 was used to demonstrate the beneficial effect of the drug, although the disease changes are at the level of small airways which is almost not expressed by the measurement FEV1.~Purpose of the study~To estimate the damage severity at the small airways.~To estimate the change in quality of life.~To assess the pulmonary function changes at rest and following exercise, including parameters of air trapping (hyperinflation)~Methods & Materials Patients - Inclusion - 30 Moderate COPD (GOLD classification) , AGE 45-70, both sexes. Treated with inhaled steroids and long acting beta agonists.~Exclusion - Active ischemic heart disease, heart failure, orthopedic problems that preclude ergometric bicycle activity.~Questionnaire - The St. George questionnaire for quality of life will be used . Pulmonary function testing- Lung volumes and spirometry un including inspiratory capacity will be measured before and after exercise.~Study protocol - 2 weeks run in, for observation disease stability and drug adherence.~Patient will randomly separated in 2 groups . Group A - will receive 600-1200 mg N-acetyl cystein twice daily. Group B - will receive as control placebo . Following 4 weeks of treatment patient will clinically re-examined and PFT's performed as described. After 2 weeks of washout group A. will serve as control and group B. will be treated with NAC as described.

Treatment of COPD patients depends on the stage of the disease. First of all it is strongly recommended quit smoking, then bronchodilators drugs are added. In more advanced stages inhaled corticosteroids and pulmonary rehabilitation are added. In hypoxemic patients a long term supplemental oxygen is advised.~The addition of sputum modifiers drugs is equivocal, since no objective improvement was documented.~N-Acetylcystein (NAC) is a drug known for its anti-oxidant and mucolytic activity. In animal models of disease it showed its beneficial activity , whereas in human such changes weren't demonstrated. In all the studies FEV1 was used to demonstrate the beneficial effect of the drug, although the disease changes are at the level of small airways which is almost not expressed by the measurement FEV1.~Purpose of the study~To estimate the damage severity at the small airways.~To estimate the change in quality of life.~To assess the pulmonary function changes at rest and following exercise, including parameters of air trapping (hyperinflation)~Methods & Materials Patients - Inclusion - 30 Moderate COPD (GOLD classification) , AGE 45-70, both sexes. Treated with inhaled steroids and long acting beta agonists.~Exclusion - Active ischemic heart disease, heart failure, orthopedic problems that preclude ergometric bicycle activity.~Questionnaire - The St. George questionnaire for quality of life will be used . Pulmonary function testing- Lung volumes and spirometry un including inspiratory capacity will be measured before and after exercise.~Study protocol - 2 weeks run in, for observation disease stability and drug adherence.~Patient will randomly separated in 2 groups . Group A - will receive 600-1200 mg N-acetyl cystein twice daily. Group B - will receive as control placebo . Following 4 weeks of treatment patient will clinically re-examined and PFT's performed as described. After 2 weeks of washout group A. will serve as control and group B. will be treated with NAC as described.

This study will be performed in patients who were previously treated with SQV /r 1000/100mg twice daily or Lopinavir/r plus TDF/FTC once daily as part of the Gemini study. After 48 weeks of the study, the patients will be treated with SQV film coated tablet 1500/100mg once daily plus TDF/FTC300/200mg once daily with good CD4 and VL outcomes. In this study, we would like to evaluate the once-daily dosing of SQV using SQV- SQV film coated tablet 1500/ritonavir 100mg in combination with TDF/FTC300/200mg once daily. We believe that the PK parameters of SQV given at 1500mg daily will be equivalent to the 1000mg twice daily dosing when combined with RTV and TDF/FTC300/200mg OD, and that the once daily regimen will have better safety, tolerability profile than the twice daily regimen while maintaining good CD4 and VL outcome

Pharmacokinetic and long term efficacy of TDF SQV film coated tablet 1500/100mg once daily plus TDF/FTC300/200mg once daily.

The Bispectral Index (BIS) is an electroencephalogram-derived measure of anesthetic depth. We hypothesized that BIS can also indicate the adequacy of analgesia. Therefore we built a combined closed-loop anesthesia system using BIS as control variable and two proportional-differential control algorithms, a propofol and a remifentanil target-controlled infusion system. The effectiveness of such a closed-loop anesthesia system has been demonstrated in a prospective, randomized study.~Elimination of anesthetic agents, propofol in particular, is strongly reduced during liver transplantation. Closed-loop anesthesia could provide adequacy for requirements in respect to the various phases of transplantation. Two groups of patients are compared: one in which propofol and remifentanil are administered by the anesthesiologist, using target-controlled infusion systems, and one in which propofol and remifentanil are administered automatically by the combined closed-loop anesthesia system. In both groups the goal is to maintain BIS between 40 and 60, the range recommended by the manufacturer during anesthesia. We expect the combined closed-loop anesthesia system group to do better: i.e. diminished consumption of propofol (primary outcome measure).

To compare closed-loop anesthesia to manual administration of propofol and remifentanil during liver transplantation

The objective is to assess the safety of a monovalent vaccine of a new 6:2 influenza virus reassortant in healthy adults prior to the release of the trivalent vaccine (FluMist®) containing it.

To assess the safety of a vaccine in healthy adults prior to the release of the vaccine (FluMist®) containing it.

Prostate biopsy is usually conducted as an ambulatory transrectal needle aspiration, ultrasonography guided. The area is not sterile, with high concentration of gram-negative and anaerobic pathogens, infection can be induced during the procedure to the urinary tract, and even cause bacteremia.~Prior studies concluded that prophylaxis antibiotic against gram-negative bacteria decreased significantly the amount of infections and hence it is accepted to give prophylaxis antibiotics which will cover especially gram-negative bacteria. Other studies show decrease in infections percent in patients that received prophylaxis opposed to those who did not, from 5-30% to less than 1%. Yet, there was no significant difference between those who received one dose and those who were treated for 3-5 days. Quinolones are considered preferred treatment since they can be given orally, but there is already an increase in resistance rates. TMP-SMX can not be used empirically due to a high percent of resistant uropathogens. One of the options is aminoglycosides, especially gentamicin. Advantages: very low resistance rate in the community, high concentration is urinary tract, slow clearance, no resistance developed under treatment, chip and with very few side effects.

Prostate biopsy is usually conducted transrectal, ultrasonography guided. Since the area is not sterile, infection can be induced during the procedure.~Prophylaxis antibiotic against gram-negative bacteria decreased significantly the amount of infections. Quinolones are considered preferred treatment but there is already an increase in resistance rates. TMP-SMX can not be used empirically due to a high percent of resistant uropathogens. One of the options is aminoglycosides, especially gentamicin. Advantages: very low resistance rate in the community, high concentration is urinary tract, slow clearance, no resistance developed under treatment, chip and with very few side effects.

Background- Meatal stenosis requiring surgery occurs more often in circumcised than in uncircumcised boys, with an estimated rate of 7.3%. At our institute, meatotomy is usually performed under general anesthesia and penile block is routinely added after induction. Recently, several reports have described the performance of meatotomy as an office procedure under local anesthesia, with good patient tolerability and a considerable reduction in operative time and costs.~Purpose - The aim of the study is to prospectively investigate the feasibility, pain control, and outcome of meatotomy performed under sedation and local anaesthesia compared with general anaesthesia with and without patient block.~Materials and Methods- The study population will include 75 otherwise healthy boys aged 3 years to 15 years scheduled for meatotomy at our institute. Children with ASA grade >2 will be excluded. The children will be reexamined by a senior pediatric ulologist to confirm the need for surgery. All children and their parents will be given a detailed explanation of the procedure and of the anesthesia and pain control options available by a urology nurse, pediatric urologist, and anesthesist.~Prior to surgery, study participants will be randomly allocated to one of the following groups:~Group 1 will include 25 patients who will undergo meatotomy under sedation and local anesthesia. The penis will be topically treated with EMLA cream one hour before surgery and then covered with tegaderm. In children aged 3-5 years, sedation will consist of midazolam 0.5 mg/kg (up to 10 mgs) p.o., administered 20 minutes before surgery; children aged 5 years and older will receive nitrous oxide (up to 60%) with oxygen. All patients will be connected to a pulse oximeter and monitored by a sedation nurse or an anesthesist.~Group 2 will include 25 boys operated on under general anaesthesia. Anesthesia will be induced by Sevoflurane 8% or IV propofol 2 mg/kg and maintained with sevoflurane 3% or isoflurane 1% and nitrous oxide. Ropivacaine 0.2% 1 cc-5 cc will be administered for penile block following induction.~Group 3 will include 25 boys operated on under general anesthesia, like group 2, but without penile block.~All children in all groups will receive paracetamol 15 mg/kg (up 500 mg) as suppository or suspension after completion of the meatotomy, and will be monitored by a sedation nurse until they are fully recovered. They will be discharged from the hospital after a successful spontaneous void.~Prior to patient discharge, the parents will be asked to complete a form grading their child's current pain level and their general satisfaction with the procedure (Appendix I). Boys older than 5 years will be asked to complete their own pain scale as well.~Twenty-four hours after surgery, the parents will be asked, by telephone, to again grade their child's current pain; to report the type and doses of pain medications used within this time frame, to score their child's voiding quality; and to rate their general satisfaction (Appendix II).~All patients will be invited for a follow-up visit at the clinic one month after the procedure. At that time, a urologist will assess the meatal width and voiding quality (Appendix III).

The aim of the study is to prospectively investigate the feasibility, pain control, and outcome of meatotomy performed under sedation and local anaesthesia compared with general anaesthesia with and without patient block

In human breast milk, and in most infant formulas more than 98% of this milk fat is in the form of triglycerides, which contain saturated and unsaturated fatty acids esterified to glycerol. Fatty acids in human milk-fat have a highly specific positional distribution on the glycerol backbone and this specific configuration is known to have a major contribution to the efficacy of this nutrient absorption.~Palmitic acid (C16:0), the major saturated fatty acid, is predominantly esterified to the sn-2 (β) position of the triglyceride in human milk. In contrast, palmitic acid in standard infant formulas is esterified to the sn-1 and sn-3 positions.~Infants fed with high sn-2 palmitic acid formula had softer stools, less constipation and better calcium absorption as compared to standard infant formula.~InFat™ is structured triglyceride fat ingredient with high levels of palmitic acid at sn-2 position.~The primary objective of this trial is to demonstrate that feeding Chinese term infants, with formula having proportion of palmitate in the sn-2 position comparable to human milk, reduces calcium-soaps formation.

The purpose of this study is to demonstrate the efficacy of infant formula having proportion of palmitate in the sn-2 position comparable to human milk in Chinese term infants.

Percutaneous transluminal angioplasty (PTA) is a minimally invasive technique for treatment of superficial femoropopliteal artery (SFA) obstructions or occlusions in patients with intermittent claudication as well as critical limb ischemia. Initial technical success rates of above 95% can be achieved and acceptably low rates of complications are consistently reported in the literature. There is a direct relation between treated vessel length and patency rates. One year patency of lesions longer than 10cm has only been 22% at one-year follow up. This major drawback limits a widespread applicability of PTA, and the indication of PTA particularly in patients with intermittent claudication is discussed controversially.~With the introduction of endovascular stents, the problems of elastic recoil and residual stenoses due to arterial dissection could be resolved and initial reports of stenting for the treatment of occlusive atherosclerotic disease of the SFA showed promising results with primary and secondary patency rates of 87% to 90% after 18 months. However, subsequent studies demonstrated that exaggerated neo-intimal hyperplasia in the stented segment frequently leads to instent restenosis. This condition will be of greater importance with increasing number of stent implantation procedures during the last years. Repeated PTA of instent restenosis is performed for revascularisation in these patients, but the gold standard for treatment of instent restenosis is unknown and the rate of recurrence after repeat treatment of instent restenosis remains high. The concept of cutting balloon seems appealing for this indication, as the balloon-mounted microtomes guarantee smooth lumen gain within the stent, without the risk of vessel wall perforation (due to the protecting effect of the stent as the outer limit for the microtomes).~Initial reports of the use of the cutting balloon for the treatment of occlusive atherosclerotic disease of the SFA show promising results, indicating that the problems of elastic recoil and residual stenoses due to arterial dissection might be resolved. The cutting balloon has four tiny microtomes (< 0.1mm height) on the outside, which cut the fibrous plaque during expansion of the balloon. Consequently the problem of elastic recoil is ideally addressed, additionally less trauma is exercised on the vessel wall during dilatation of the balloon. This might be achieved by a reduction of vessel wall trauma, vessel wall inflammation and consequently reduced neointimal formation. The cutting balloon can be used for pre-dilatation with diameters slightly less than the target vessel diameter, but still cuts the fibrous plaque, the desired target vessel diameter is then achieved by final touch up dilatation with a standard angioplasty balloon. In the coronary arteries the cutting balloon has been used in randomized studies comparing CB-PTCA to PTCA, as well as in trials for the treatment of in-stent restenosis. All of these trials demonstrated the safety and efficacy of the cutting balloon, only larger randomized trials failed to proof superiority to conventional PTCA. Data in the peripheral arteries are at least scarce. Although the indications for CB-PTA in the SFA includes significant residual stenosis or in-stent restenosis, there are currently no published randomized controlled trials (RCT) comparing PTA vs. cutting balloon angioplasty (CB-PTA) for any specific condition. This lack of data led us to initiate a RCT comparing primary PTA vs. CB-PTA for treatment of in-stent restenoses in patients with intermittent claudication or critical limb ischemia with TASC category A-B in the femoropopliteal artery . The primary endpoint is the occurrence of restenosis as an ultrasonographic reduction of the vessel lumen diameter >50% within 6 months after endovascular treatment. In addition, the course of postintervention inflammation as indicated by serum levels of C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen will be assessed.~STUDY DESIGN, INCLUSION AND EXCLUSION CRITERIA. Patients with in-stent restenosis (ultrasonographic stenosis > 50% of the vessel lumen diameter) after prior PTA and Stent placement of the SFA will be enrolled to this single-center prospective RCT. The protocol has to be approved by the institutional ethics committee and all patients have to provide written informed consent before enrollment. Entry criteria include symptomatic peripheral artery disease with intermittent claudication (Fontaine stage IIa or b), or critical limb ischemia related to a recurrent stenosis in a previously stented segment of up to 20 cm length. Exclusion criteria history of intolerance of anti-platelet therapy, or adverse reaction to heparin, bleeding diathesis, creatinine >2.5 mg/dL, hemodialysis, active bacterial infection, and allergy to contrast media, pregnancy and disability to give informed consent.~FOLLOW-UP. ABI testing, treadmill exercise, and Duplex-sonography of the treated vessels will be performed in all patients at 1, 3, and 6 months after treatment. A peak systolic velocity of ≥ 2.4 was considered indicative of a >50% narrowing and was defined as indicative of a restenosis10. Reintervention or surgical bypass at the treated segment are also defined as a restenosis and loss of primary patency. An improvement of at least one Fontaine category above baseline is used to define clinical success in association with maintenance of at least a 0.15 increase in exercise ABI from the preprocedure level.~COMPLICATIONS are classified as either major or minor (as described in Appendix A). Major complications are e.g. bleedings at the puncture side with hematoma and a decrease of serum hemoglobin more than 2 g/dl, loss of stent in the artery , vessel rupture, amputation, macroembolisation with need for further revascularisation and life threatening bleeding complications.~STUDY ENDPOINTS. The primary study endpoint is the occurrence of a >50% restenosis at the treated segment at 6 months post-intervention as determined by duplex ultrasound (in-segment restenosis). Secondary objectives are primary technical success rates (residual stenosis <30% without need for secondary stent implantation, primary assisted and secondary patency, clinical patency, target vessel and target lesion revascularization, and cardiovascular adverse events at 1, 3, and 6 months after the procedure. Furthermore, the course of inflammatory parameters will be assessed.

Percutaneous transluminal angioplasty (PTA) is a minimally invasive technique for treatment of superficial femoropopliteal artery (SFA) obstructions or occlusions in patients with intermittent claudication as well as critical limb ischemia. Initial technical success rates of above 95% can be achieved and acceptably low rates of complications are consistently reported in the literature. There is a direct relation between treated vessel length and patency rates. One year patency of lesions longer than 10cm has only been 22% at one-year follow up. This major drawback limits a widespread applicability of PTA, and the indication of PTA particularly in patients with intermittent claudication is discussed controversially.With the introduction of endovascular stents, the problems of elastic recoil and residual stenoses due to arterial dissection could be resolved and initial reports of stenting for the treatment of occlusive atherosclerotic disease of the SFA showed promising results with primary and secondary patency rates of 87% to 90% after 18 months. However, subsequent studies demonstrated that exaggerated neo-intimal hyperplasia in the stented segment frequently leads to instent restenosis. This condition will be of greater importance with increasing number of stent implantation procedures during the last years. The concept of cutting balloon seems appealing for this indication, as the balloon-mounted microtomes guarantee smooth lumen gain within the stent, without the risk of vessel wall perforation. Initial reports of the use of the cutting balloon for the treatment of occlusive atherosclerotic disease of the SFA show promising results, indicating that the problems of elastic recoil and residual stenoses due to arterial dissection might be resolved. The cutting balloon has four tiny microtomes (< 0.1mm height) on the outside, which cut the fibrous plaque during expansion of the balloon. Consequently the problem of elastic recoil is ideally addressed, additionally less trauma is exercised on the vessel wall during dilatation of the balloon. This might be achieved by a reduction of vessel wall trauma, vessel wall inflammation and consequently reduced neointimal formation. Although the indications for CB-PTA in the SFA includes significant residual stenosis or in-stent restenosis, there are currently no published randomized controlled trials (RCT) comparing PTA vs. cutting balloon angioplasty (CB-PTA) for any specific condition. This lack of data led us to initiate a RCT comparing primary PTA vs. CB-PTA for treatment of in-stent restenoses in patients with intermittent claudication or critical limb ischemia with TASC category A-B in the femoropopliteal artery .

Blood sampling heel lance for neonatal screening is the most frequent painful manoeuvre in Neonatal Units in healthy neonates.~Some techniques showed efficacy evidence in reducing pain response: sucrose solutions, breastfeeding during blood sampling, topical local anaesthetics.~A Cochrane Review in 2004 recommends the administration of sucrose 0.24-0.48 g (1-2 ml of 24% sucrose solution). It reduces PIPP scale rate about 20%.~Our purpose is to compare the antinociceptive effect of 1 ml 30% sucrose solution administered 2 minutes before heel lancing vs blood sampling heel lance during breastfeeding.~PIPP scale is a validated 7-indicator scale for the assessment of procedural pain in preterm and term neonates.~Informant consent was asked parents during consultation by a Pediatrician of the Neonatal Unit of the Hospital in the last months of pregnancy.~After parent written consent was obtained, 100 three day old neonates were randomized for treatment A (breastfeeding) or B (sucrose solution administration). The nurse opened consecutively numbered envelopes.~Timing of operators: Group A Breastfeeding~The heel of neonate was warmed up by a glove full of water at 40° C for 2 minutes.~Monitoring of Oxygen Saturation and Heart Rate.~The neonate was breastfed by the mother till the nurse watched a continuous active suction.~Administration of first phase of PIPP scale (15 seconds before heel lance).~Digital Voice Record started~Heel Lance with an automated piercing device .~Squeezing for blood sampling till filling 4 catch basins for neonatal screening. If necessary a new heel lance was practiced.~Administration of the second phase of PIPP scale.~Record of duration of blood sampling and collateral effects~Stop Digital Voice Recording~Group B Sucrose administration~The neonate was laid on a baby-changing table.~The heel of neonate was warmed up by a gloves full of water a 40° C for 2 minutes.~Oral administration of 1 ml of 30% sucrose solution.~Monitoring of Oxygen Saturation and Heart Rate.~Administration of first phase of PIPP scale (15 seconds before heel lance).~Digital Voice Record starts~Heel Lance with an automated piercing device.~Squeezing for blood sampling till filling 4 catch basins for neonatal screening. If necessary a new heel lance was practiced.~Administration of the second phase of PIPP scale.Record of duration of blood sampling and collateral effects.~Stop Digital Voice Recording~Blood sampling was practiced by skilled pediatric nurses. Registration of data, PIPP scale, voice record was made by a second operator, blind to the pur pose of the study.~A third blind operator collected paper data and checked voice record (outcome cry behaviour).

The purpose of this study is to compare the antinociceptive effect of 1 ml of 30% sucrose solution vs breastfeeding on neonatal screening heel lance

This is a phase I, double-blind, stratified, parallel group, placebo-controlled repeat dose study in a minimum of 8 circumcised and 8 uncircumcised healthy male volunteers. Subjects will attend 2 study visits, of which 1 will be a Screening Visit (Visit 1) and the other, a consecutive 21-day treatment visit (Visit 2; Days 1-21) which commences no more than 14 days after the Screening visit. Subjects will reside in the phase I unit throughout the treatment period. The duration of each subject's participation in the study will be up to 5 weeks.~Subjects are stratified based on whether they are circumcised or uncircumcised and within each stratified group subjects are randomized to PSD502 (lidocaine prilocaine spray) or placebo in a 3:1 ratio.~Procedures during the 21 day treatment period include: visual examination of the glans penis, blood sample collection for pharmacokinetic analysis of lidocaine and prilocaine, swabbing of the glans penis for residual PSD502, vital signs and 12-lead ECG, adverse event enquiries and collection of concomitant medications. Subjects are discharged from the clinic on Day 21 following a safety evaluation.

The main objective of the study is to determine the safety and tolerability of repeated application of PSD502 to the glans penis in healthy male volunteers

Abdominal hot compresses are traditionally used by patients with liver diseases as self help. This study investigated the effect of abdominal hot compresses on hepatic blood flow measured by elimination of indocyanine green (ICG), a non-toxic green dye. It was presumed, that abdominal hot compresses increase hepatic blood flow either by local vasomotor-reflex or by decreasing the tone of the sympathetic nerve system.~In healthy volunteers ICG elimination was measured with and without hot compress at two investigations in a weekly interval. At each investigation ICG was injected as bolus after a rest period of 10 minutes. After the injection blood was taken in regular intervals for analysis of ICG concentration over a period of 40 minutes and half life was calculated.~The time interval between the investigations was 8 days, the sequence was randomly assigned.

We investigated, whether abdominal hot compresses effect hepatic blood flow. Our hypothesis was, that the hot compresses might either by local vasomotor-reflex or by decreasing the tone of the sympathetic nerve system increase hepatic blood flow.

The prevalence of diabetes mellitus and impaired glucose tolerance are nearing epidemic proportions in developed societies. For example in the USA >16 million individuals have diabetes and this number is predicted to double over the next two decades. Diabetes is a major risk factor for death and disability, primarily from cardiovascular disease (CVD).~The mechanisms of how diabetes increases the risk of developing CVD are not fully understood. It is evident from previous studies that diabetes has an adverse effect on both artery and heart function. What is emerging from recent studies is that it is likely that these proven dysfunctions in the arteries and heart interact to increase the risk of CVD.~Insulin-sensitizing agents, such as Pioglitazone, may have a beneficial effect on heart and artery function. This study aims to further our understanding of the effect of these agents on heart and artery using a novel, sensitive, non-invasive scanning technique to investigate the effects of this group of drugs on heart and artery function.~This is a prospective double-blind randomised crossover study comparing the insulin-sensitizing drug, Pioglitazone with a placebo in 24 volunteers. Following a >1 week run-in period subjects will be randomised double-blind to 1 of 2 treatment sequences. Subjects will either receive the active drug (Pioglitazone 45mg/day) for a 12 week period, followed by a 2 week washout and then the placebo drug for 12 weeks OR they will receive the placebo drug for 12 weeks, followed by the 2 week washout and 12 weeks of the active drug (Pioglitazone 45mg/day).~This design was chosen to test the null hypothesis that the active drug will have no effect on diastolic heart function. The use of a placebo is essential to ensure that any benefits found can be attributed to the active drug. The design also allows us to minimise the number of subjects needed and is the gold standard approach to avoid observer bias.

This study aims to use a novel, sensitive, non-invasive scanning technique to investigate the effects of insulin-sensitizing agent pioglitazone, on heart and artery function.

This study is for patients with breast, prostate, ovarian, non-small cell lung (NSCL) or bladder cancer who have failed potentially curative treatments or for whose disease a curative treatment does not exist.~OGX-427 is a second-generation ASO that inhibits expression of Hsp27. Hsp27 is one of the heat shock proteins. Hsp27 increases with cell stress, including cytotoxic chemotherapy, radiation therapy and hormone therapy and has been shown to inhibit cell death. Thus, decreasing Hsp27 as a cancer therapy is attractive as a therapy as it should result in down regulation of pathways implicated in cancer progression and development of resistance to treatment.~A number of in vitro and in vivo pharmacological studies have demonstrated that OGX-427 has single-agent activity in reducing Hsp27, inhibiting cell growth and inducing cell death in several human cancer cell lines. OGX-427 has also demonstrated chemosensitizing activity in studies using cell lines and animal models in combination with several cytotoxic drugs, including docetaxel.~Docetaxel (Taxotere®) has anticancer activity in breast, prostate, ovarian, non-small cell lung and bladder cancer. Docetaxel has been approved by Health Canada and the Food and Drug Administration for the treatment of patients with breast, prostate, ovarian and non-small cell lung cancer.

This study is for patients with cancer who have failed potentially curative treatments or for whose disease a curative treatment does not exist.~OGX-427 is an antisense product that inhibits expression of one of the heat shock proteins. Decreasing this heat shock protein (Hsp27) should result in down regulation of pathways implicated in cancer progression and development of resistance to treatment.

Dexamethasone decreases inflammation and also suppresses the immune system.~If you are found to be eligible for this study, you will be randomly assigned (as in the toss of a coin) to receive either dexamethasone or a placebo by mouth in the morning and at night with food every day for 14 days. A placebo is a substance that looks like the study drug but which has no active ingredients. You will have an equal chance of being placed in either of the 2 groups. You, the medical staff, and researchers will not know to which group you have been assigned.~Beginning on Day 15 [± 3 days], regardless of if you were assigned to the dexamethasone or placebo group during the first 14 days, you will begin receiving the dexamethasone. On Days 15-21, you will receive dexamethasone 2 times a day. On Days 22-28 you will continue to take dexamethasone 2 times a day, but it will be at a lower dose level.~If you develop intolerable side effects while on this study, the medication will be stopped and you will be removed from the study.~You will be asked to return to the outpatient clinic on Days 8 [± 3 days], 15 [± 3 days] , 22 [± 3 days], and 29 [± 3 days] to answer a questionnaire about your cancer diagnosis, the medication you are taking, and the symptoms you are having (for example, pain, fatigue, nausea, appetite problems, sleep problems, depression, and your overall sense of well-being). The questionnaire will take approximately 30 minutes to complete. Blood (about 1 tablespoon) will be drawn to measure protein levels and to check the iron level in your blood. If you are unable to return to the clinic on days 8, 15, 22, or 29; the assessments will be done by the research nurse by phone; the blood work will not be done.~You will be considered off-study on Day 29 [ ± 3 days]. All study patients will have a 2 week follow-up on day 43 [± 3 days] after study drug has been discontinued, for safety and toxicity assessments. If you are unable to return to the clinic on day 43, the research nurse will do the safety and toxicity assessment by phone.~This is an investigational study. Dexamethasone has been approved by the FDA and is a commercially available drug. It is FDA approved at this dose level. Its use in this study, for this purpose, is investigational. About 160 patients will take part in this study. Up to 110 will be enrolled at the University of Texas (UT) MD Anderson Cancer Center. The other sites participating in this study are Lyndon Baines Johnson [LBJ] breast oncology clinic Houston Texas, and Four Seasons Hospice in Flat Rock, North Carolina.

The goal of this clinical research study is to learn if dexamethasone can help to control symptoms such as fatigue, pain, nausea, weight loss, loss of appetite, sleep problems, and/or depression in patients with advanced cancer.

Neodajuvant chemotherapy with gemcitabine / cisplatin is applied to patients with resectable cancer of pancreatic head. Two cycles of chemotherapy are given on day 1 and 15 each. After restaging excludes disease progression, a standard Whipple procedure is performed.~Staging and restaging procedures include abdominal CT, diagnostic laparoscopy, PET/CT, tumor markers (CEA, CA 19-9) and assessment of the quality of life by the QLQ-30.~Trial with medicinal product

Neodajuvant chemotherapy with gemcitabine / cisplatin is applied to patients with resectable cancer of pancreatic head.

Cultivated autologous oral mucosal epithelial sheets on amniotic membrane have been reported to have good clinical results in treating patients with ocular surface disorders in both human or animal studies, and such technique has not been used in our hospital, the main purpose of this study is to use these cell sheets to treat patients with severe surface disorders, which include limbal insufficiency induced corneal surface problem, and symblepharon caused by severe conjunctival epithelial insufficiency. We will first choose patients who meet the surgical criteria, and these patients need to receive dental examination three months before surgery. Two weeks before transplantation, the oral mucosa tissue will be obtained by a dentist and the oral mucosal epithelial cell sheets will be cultivated on amniotic membrane until reaching confluency and stratification. During the transplantation surgery, the abnormal fibrovascular tissues on the ocular surface will be removed. The areas of symblepharon will also be released. The cultivated oral mucosal cell sheets will be transplanted on the denuded corneal surface or the scleral surface of the symblepharon area. Therapeutic contact lenses will be applied after surgery. After operation, the patients will be admitted for about two weeks. After discharge, the patients need to receive regular follow up weekly during the first two months, followed by biweekly follow up until postoperative 6 months. Afterward, the patients need to receive monthly follow up until postoperative 2 years. During the follow up, the data of the patients' visual acuity, intraocular pressure, slit lamp biomicroscopic findings, and in vivo confocal microscopic data will be obtained. The project plans to start from July 1st 2007 until June 30th 2010. We plan to enroll totally 20 patients.

Since cultivated autologous oral mucosal epithelial sheets on amniotic membrane have been reported to have good clinical results in treating patients with ocular surface disorders in both human or animal studies, and such technique has not been used in our hospital, the main purpose of this study is to use these cell sheets to treat patients with severe surface disorders, which include limbal insufficiency induced corneal surface problem, and symblepharon caused by severe conjunctival epithelial insufficiency. We will first choose patients who meet the surgical criteria, and these patients need to receive dental examination three months before surgery. Two weeks before transplantation, the oral mucosa tissue will be obtained by a dentist and the oral mucosal epithelial cell sheets will be cultivated on amniotic membrane until reaching confluency and stratification. During the transplantation surgery, the abnormal fibrovascular tissues on the ocular surface will be removed. The areas of symblepharon will also be released. The cultivated oral mucosal cell sheets will be transplanted on the denuded corneal surface or the scleral surface of the symblepharon area. Therapeutic contact lenses will be applied after surgery. After operation, the patients will be admitted for about two weeks. After discharge, the patients need to receive regular follow up weekly during the first two months, followed by biweekly follow up until postoperative 6 months. Afterward, the patients need to receive monthly follow up until postoperative 2 years. During the follow up, the data of the patients' visual acuity, intraocular pressure, slit lamp biomicroscopic findings, and in vivo confocal microscopic data will be obtained. The project plans to start from July 1st 2007 until June 30th 2010. We plan to enroll totally 20 patients.

Dark chocolate is one of the richest sources of polyphenols, for example, a standard 40g portion of dark chocolate contains 400-800 mg of polyphenols, compared to red wine (170 mg /100ml) or an apple (200 mg/piece). Cocoa polyphenols, most notably the catechins, can exist in both lipid and water-based environments (amphipathic), meaning they can spare both lipophillic and hydrophilic vitamins. There have been a number of human trials conducted using chocolate or cocoa and measuring various endpoints. Most have been conducted with dark chocolate. An article in Nature found that the bioavailability of epicatechin from milk chocolate was substantially reduced compared to dark, and even dark taken with a glass of milk (Serafini et al 2003). The hypothesis was that the milk proteins bind to polyphenols, making them unavailable. Subsequent studies have not been able to reproduce this, but none have been conducted using solid chocolate as the first study, all have been done using a drink matrix, which may completely alter the binding interactions of the polyphenols and protein. Previous bioavailability trials with dark chocolate have shown a 12 fold increase in plasma epicatechin 2 hours after consumption of 80g of chocolate containing 557 mg total polyphenols (137 mg epicatechin) (Rein et al 2000) with a concurrent increase in plasma total antioxidant capacity and a decrease in TBARS. Another study showed an increase in epicatechin 2 hours after administering 25g of chocolate chips containing 220 mg flavanols and procyanidins, with a concurrent increase in prostacyclin/leukotriene ratio and reduction in platelet-related hemostasis (Holt et al 2002).~This study is designed as a blinded, three arm crossover trial. The primary outcome measure is to compare plasma polyphenol levels after consumption of 3 chocolates (2 milk, 1 dark) while the secondary outcome measures are to characterise the time course of polyphenols in the blood and to investigate individual variation in Tmax and Cmax for use in future studies. All volunteers will try all chocolate types with a similar taste & appearance (though milk and dark are likely to still be distinguishable for the volunteer, not the investigator). Subjects will undergo medical screening, anthropometry, physical activity and dietary assessments before randomisation for the order of consumption. Bloods are to be taken as a time course for the next 24 hours, as is urine.

Dark chocolate is one of the richest sources of polyphenols though it has been hypothesised that the bioavailability of epicatechin from milk chocolate was reduced compared to dark. The primary outcome measure is to compare plasma polyphenol levels after consumption of 3 chocolates (2 milk, 1 dark) while the secondary outcome measures are to characterise the time course of polyphenols in the blood and to investigate individual variation in Tmax and Cmax for use in future studies.

Child physical abuse is a common public health problem that has been associated with significant psychosocial and physical health problems among children. Abuse-focused cognitive-behavioral therapy (AF-CBT) has been identified as an effective treatment strategy for dealing with child physical abuse. The main component of AF-CBT, cognitive behavioral therapy (CBT), is a type of psychotherapy in which everyday thoughts and behaviors are modified to improve mental health problems, such as depression or anxiety. AF-CBT uses CBT techniques to specifically focus on improving the mental health problems associated with physical abuse. In this study, AF-CBT will incorporate individual and family CBT and will be adapted by community practitioners to maximize its effectiveness in a community health care setting. This study will determine the effectiveness of AF-CBT, provided by a community health clinic, in addressing the behavioral and emotional health needs of children and adolescents whose parents have used physical disciplinary action.~Participants in this study will include practitioners, their supervisors, and their patients. Practitioners will be randomly assigned to provide either treatment as usual (TAU) or the AF-CBT intervention for 3 to 6 months. Patient participants will continue to see their regular practitioner, but will receive the type of treatment to which their practitioner has been assigned. Practitioners who are assigned to TAU will continue to attend training workshops or seminars as a part of their clinics' routine policies and their current personal practices. Practitioners who are assigned to AF-CBT will first receive training in the treatment method. The training curriculum will include a published treatment book, intensive training sessions, which will occur weekly for 8 hours over 4 weeks, handouts that illustrate key therapeutic information and exercises, and ongoing case consultation reviews for 5 months.~Parent and child participants will meet with practitioners at times to be decided based on individual patient needs. All parents and children will be asked to participate in interviews to assess symptoms and outcomes before attending any treatment sessions with the practitioner, 6 months, 12 months, 18 months,and 30 months after baseline. Parents and children will also complete questionnaires each time they meet with the practitioner. This study will also assess the ability of the practitioners and supervisors to carry out AF-CBT.

This study will determine the effectiveness of abuse-focused cognitive behavioral therapy that is provided by a community health clinic in addressing the behavioral and emotional health needs of children and adolescents whose parents have used physical disciplinary action.

Open abdomen treatment often results in difficulties in closing the abdomen. Highest closure rates are seen with the vacuum assisted wound closure (VAWC) technique. Failures with this technique is occasionally experienced, especially in cases with severe visceral swelling needing longer treatment periods with open abdomen. A novel combination of vacuum assisted wound closure and mesh mediated fascial traction for managing the open abdomen was therefore developed and initially tested in a small pilot-like study with encouraging results with late primary closure of the abdomens in all seven patients.~In this multicenter study we prospectively evaluate the technique.~Inclusion criteria:~All patients treated with open abdomen at the 4 participating hospitals are registered, and only those patients who have commenced therapy with VAWC and mesh mediated fascial traction will be included in the study in an intention to treat model.~Exclusion criteria:~Treatment of open abdomen with other techniques.~Method:~The first period of 2-5 days only the abdominal VAWC dressing is applied.~On day 3-10 a polypropylene mesh is sutured to the fascial edges, between the two layers of the VAWC system, and tightened.~The VAWC dressing is changed and the mesh tightened every 2-3 days, resulting in gradual approximation of the fascial edges.~Finally the mesh is removed and the fascia is closed.~At closure the wound to suture length is registered.~Primary endpoint:~Frequency of primary fascial closure.~Secondary endpoints:~study of factors associated with failure of fascial closure and in-hospital mortality,~abdominal pressure variation attributable to the use of the technique,~duration of treatment with open abdomen,~frequency of incisional hernia after one and five years.~Duration of the study:~3-5 years. Enrollment of open abdomen cases.~Follow-up schedule for patients:~Clinical evaluation at 1 and 5 years.~CT-examination at 1 year.

The purpose of this multicenter trial is to prospectively evaluate a novel combination of vacuum assisted wound closure (VAWC) and mesh mediated fascial traction for closure of open abdomens.

The incidence and mortality rates for invasive cervical cancer in minority, low-income, and less educated women exceeds that for white, higher income, and better educated women. In southern California the incidence and mortality rates for cervical cancer are nearly twice that of non-Latina white women. Our preliminary work supports and extends the extant literature, noting that quality of life can be significantly disrupted among cervical cancer survivors, with qualitative differences in how Latina women experience cancer survivorship. However, there is a paucity of literature on interventions designed to assist cervical cancer survivors manage illness-specific stress and improve health behaviors. Our current NIH-funded work suggests that a six session psychosocial telephone counseling (PTC) intervention can improve QOL and decrease psychological distress, with accompanying intervention-induced neuroendocrine and immune parameter modulations which may be related to disease endpoints. In primary support of these significant biobehavioral findings, the project herein proposes to accomplish the following Specific Aims:~Test the efficacy of PTC for cervical cancer survivors, compared to usual care.~Evaluate the longitudinal immune and neuroendocrine parameters in cervical cancer patients who have received PTC, compared to usual care.~Examine the longitudinal relationship between PTC associated modulations of QOL measures and biologic parameters (immune and neuroendocrine).~To achieve these aims the investigators will randomize patients ascertained through the two SEER cancer registries to PTC (N=125) or usual care (N=125), stratifying on English or Spanish language preference. Assessments will occur at baseline (9-20 months post diagnosis), and three and nine months post enrollment/baseline. Assessments will include evaluation of QOL (overall QOL, psychological distress, coping, social support, sexual functioning), health behaviors, neuroendocrine parameters dehydroepiandrosterone sulfate, growth hormone [DHEA-S, cortisol, GH] and immunologic parameters (natural killers [NK] cell activity, IL-5, interferon, human papillomavirus (HPV) E6/E7 peptides, IL-15, IL 10). This project has significant public health relevance for an important unstudied cancer survivor population, many of whom are poor and underserved. If effective, an intervention which could improve quality of life (QOL) and health behaviors, and enhance neuroendocrine and immune responses for women with cervical cancer could have significant implications toward disease recurrence or survival.

The purpose of the study is to:~Test the efficacy of psychosocial telephone counseling (PTC) for cervical cancer survivors, compared to usual care.~Evaluate the longitudinal immune and neuroendocrine parameters in cervical cancer patients who have received PTC, compared to usual care.~Examine the longitudinal relationship between PTC associated modulations of quality of life (QOL) measures and biologic parameters (immune and neuroendocrine).

Hypothesis:~Side-to-side stapled anastomosis will decrease anastomotic leak rate by 15% compared to hand sewn technique in cervical esophagogastric anastomosis~Background:~Following esophagectomy or esophageal bypass, restoration of continuity by gastric interposition with cervical esophagogastric anastomosis (CEGA) can be done either by a hand-sewn or stapled anastomosis. Regardless of the surgical approach, decreasing anastomotic complications is essential for minimizing early morbidity and improving long-term functional results and quality of life. Cervical esophagogastric anastomosis almost eliminates the risk of postoperative mediastinitis associated with anastomotic leaks. Further, 98% of CEGA leaks can be managed successfully with local wound care (1), and less than 2% are associated with serious complications such as gastric tip necrosis, cervical vertebral osteomyelitis, epidural abscess and tracheogastroesophageal fistula, etc (2). Though early complications of CEGA are less, the long-term sequelae such as anastomotic stricture occur in nearly half the patients with an anastomotic leak. The need for life long esophageal dilatation negates the benefit of an operation intended to relieve dysphagia. The cause of anastomotic dehiscence in CEGA is possibly multifactorial (3,4) with both local tissue and systemic factors are being implicated. As the esophagus has no serosa, its longitudinal muscles hold sutures poorly and the awkward surgical exposure, possibly contribute to the higher anastomotic leak rates. Surgical technique is thus likely to play an important role. The incidence of CEGA leakage with hand sewn has been reported from 15% to 25% (5). While the stapled anastomosis is considered to be more expedient, less traumatic to tissues, with lower leak rates and associated with less mortality and morbidity, they are criticized for increased cost and high stricture rates. Most reports prior to 2000 showed identical leak rates in patients having a hand-sewn or stapled anastomosis with higher stricture rate in the stapled group (6-8). With recent technical refinements the CEGA has been performed in side-to-side manner using the Auto-Suture Endo-GIA 30-3.5 stapler. Following side to side anastomosis the leak rates have been reported to be less than 5%, with lower incidence of anastomotic stricture after leak and improved satisfaction in swallowing compared to hand sewn technique (9). These studies were retrospective and demanded a randomized trial to confirm the results. We therefore planned a randomized trial comparing the anastomotic sequelae after hand-sewn anastomosis with mechanical stapled side-to-side anastomosis~Objective:~To compare the rates of anastomotic leaks and postoperative benign stricture after CEGA done by hand-sewn (end-to-side) technique or by linear stapled anastomosis (side-to-side) technique.~PATIENTS AND METHODS:~All the patients who attended outpatient department of GI Surgery with complaints of dysphagia will be evaluated for esophageal disorder. After confirming the diagnosis of esophageal cancer and decision of esophagectomy, patients will be included in our study.~Inclusion criteria i Any patient with resectable carcinoma of the mid or lower thoracic esophagus and gastro-esophageal junction. ii Benign esophageal lesion where esophageal resection was beneficial and feasible.~Exclusion criteria i Patients who had upper thoracic or cervical esophageal carcinoma ii Unresectable lesions (T4/M1) iii Prior gastric surgery iv Poor performance status (ECOG 3,4) Sample size calculation The number of patients to be included was calculated to be 87 patients in each group based on the assumption that anastomotic leak rate will be reduced to 5% using side-to-side stapled anastomosis. The sample size was calculated by the formula for a power of 80% and alpha error of 0.05.~They will be randomly divided into two groups using computer generated random numbers.~Group A Hand sewn anastomosis; Group B Stapled anastomosis Written informed consent will be obtained from each patient before entry into the study.~Diagnostic work up and preoperative preparation The diagnostic work-up will include barium swallow, upper gastrointestinal (UGI) endoscopy and biopsy (where malignancy was suspected), hypopharyngoscopy (for corrosive stricture of esophagus), as well as haemogram, serum chemistry, liver function tests, ECG, chest x-ray and pulmonary function tests. In the malignant group, preoperative imaging will also include computed tomography (CT) scan from the neck to the upper abdomen including the liver and celiac axis. Preoperative nutrition will be maintained and if required a ryle tube or feeding jejunostomy will be done. Incentive spirometry, steam inhalation, bronchodilators and antibiotics will be used to improve the pulmonary status as required.~At surgery, the operative procedures, time taken for anastomosis and total operating time will be recorded. After surgery, patients will be assessed for anastomotic leakage by a radiographic contrast (gastrografin) study to be performed on seventh postoperative day. Anastomotic leakage will be defined as a radiological defect at the anastomotic site or leakage of swallowed fluid out of the drain site or cervical wound. Other complications, including cardiopulmonary morbidity, septic complications, duration of hospital stay after surgery and operative mortality will also be studied. Operative mortality included all patients who will die within 30 days of the procedure or during the same hospital admission. Anastomotic stricture will be defined as failure to pass the esophagoscope through the anastomosis or anastomotic narrowing requiring dilatation to relieve dysphagia.~Surgical technique:~The surgical approach will be either transhiatal or transthoracic esophagectomy. The gastric conduit will be prepared based on the right gastric and right gastroepiploic vessels and pyloromyotomy and pyloroplasty will not performed except in patients with corrosive strictures. Finger dilatation of pylorus will be done when required. The conduit will be prepared using 75-mm linear cutter. The stomach will be brought up into the neck through either the retrosternal or posterior mediastinal route. The CEGA will be done by a side-to-side stapled or end-to-side hand-sewn method. Chest tubes (32F) will be inserted bilaterally to take care of any breach in the pleura. Feeding jejunostomy (Witzel's type) with 12F Malecot's catheter will be done in all patients. The neck wound will be closed loosely with interrupted 3-0 vicryl sutures over a 14F suction drain and the skin will be approximated with skin staplers.~Hand-sewn anastomosis: A proper site on the anterior wall of stomach away from the stapled line approximately 2 cm below the highest point of the gastric conduit will be anastamosed to esophagus Posterior interrupted seromuscular sutures will be taken with 3-0 silk. The stomach will then be opened transversely (2.5 to 3 cm long). Interrupted stitches with full thickness of the stomach and esophagus will be placed to achieve mucosa to mucosa approximation. A 16F nasogastric tube will then be placed across the anastomosis into the intrathoracic stomach. The anterior wall of the anastomosis will be completed in a manner similar to posterior wall.~Stapled anastomosis: At least 5 cm of the mobilized stomach will be placed in the neck. Three interrupted seromuscular sutures will be taken between the posterior wall of the esophagus and anterior wall of stomach well away from the gastric staple line. A 1.5 cm gastrotomy will be made. Two stay sutures will then be taken, one at the anterior corner of the esophagus and another between the posterior corner of esophagus and the middle of the gastrotomy. These stay sutures will be retracted downwards as the stapler device (using Endopath, EZ45 Endoscopic Linear Cutter) will be introduced, the thinner portion into the stomach and the thicker staple-bearing portion into the esophagus. The staple cartridge will then be rotated so that the posterior wall of the esophagus and the anterior wall of the stomach will align in a parallel manner, keeping the site of the anastomosis well away from the gastric staple suture line and fire the stapler. A 16F nasogastric tube will be placed across the anastomosis into the intrathoracic stomach, and the anterior edges of the gastrotomy and open esophagus will be approximated in two layers with interrupted 3-0 silk.~Postoperative management: The nasogastric tube will be removed on the 3rd postoperative day. Jejunostomy trial feed will be started intestinal activity will appear. If there is no obvious leak, bedside test feeding with water will be done on the 5th postoperative day. If bedside test feeding shows no leak, oral feeding will be started gradually with water, banana, curds and soft diet. A contrast study will be done on the 7th postoperative day unless there is an obvious anastomotic leak. The neck drain will be removed after the contrast study. If a leak is identified, the cervical wound will be opened to establish external drainage of any cervical abscess and anastomotic fistulae. Regular dressing with normal saline soaked gauze will be done. If there is no clinical leak but the contrast study shows a contained leak (type 1 leak), patients will be managed conservatively without opening the cervical wound.~Follow up:~All patients will be followed one week after discharge and at 3-month intervals for the first two years. Routine clinical examination, hemogram and liver function tests will be done in all patients. Dysphagia will be assessed with barium swallow and esophagoscopy. Anastomotic strictures will be dilated with endoscopic or by a Foley catheter balloon (This technique has been adapted for home based self dilatation) (10).~Statistical analysis:~Continuous variables will be reported as Mean with Standard Error of Mean (SEM). Categorical variables will be reported as proportions. Student's t test, Chi-square tests and Fisher's exact test where appropriate will be used for comparison between groups. A p value of 0.05 or less will be regarded as significant.~REFERENCES~Orringer MB, Lemmer JH. Early dilation in the treatment of esophageal disruption. Ann Thorac Surg 1986;42:536-9~Iannettoni MD, Whyte RI, Orringer MB. Catastrophic complications of the cervical esophagogastric anastomosis. J Thorac Cardiovasc Surg 1995;110:1493-1501~Dewar L, Gelfand G, Finley RJ, Evans K, Inculet R, Nelems B. Factors affecting cervical anastomotic leak and stricture formation following esophagogastrectomy and gastric tube interposition. Am J Surg 1992;163:484-9~Gupta NM, Gupta R, Rao MS, Gupta V. Minimizing cervical esophageal anastomotic complications by a modified technique. Am J Surg 2001;181:534-9~Orringer MB, Marshall B, Iannettoni MD. Transhiatal esophagectomy: clinical experience and refinements. Ann Surg 1999;230:392-403~Fok M, Ah-Chong AK, Cheng SW, Wong J. Comparison of a single layer continuous hand-sewn method and circular stapling in 580 oesophageal anastomosis. Br J Surg 1991;78:342-5~Law S, Fok M, Chu KM, Wong J. Comparison of hand-sewn and stapled esophagogastric anastomosis after esophageal resection for cancer: a prospective randomized controlled trial. Ann Surg 1997;226:169-73~Beitler AL, Urschel JD. Comparison of stapled and hand-sewn esophagogastric anastomoses. Am J Surg 1998;175:337-40~Orringer MB, Marshall B, Iannettoni MD. Eliminating the cervical esophagogastric anastomotic leak with a side-to-side stapled anastomosis. J Thorac Cardiovasc Surg 2000;119:277-88~Shad SK, Gupta S, Chattopadhyay T Self-dilatation of cervical oesophagogastric anastomotic stricture: a simple and effective technique. Br J Surg 1991;78:1254-5

Carcinoma esophagus is a common cause of dysphagia. Once dysphagia occurs, a majority of the tumours are advanced. Most of them would require some form of treatments for control of dysphagia and to improve the quality of life. Surgery is the only hope for cure. It requires complete removal of the esophagus. After removal of the esophagus, the stomach can be used as a substitute for the esophagus. Anastomosis can be done in the neck either by a hand-sewn or by a stapled anastomosis. The anastomotic leak rates reported in studies comparing hand-sewn with stapled anastomosis are variable. Many non-randomized studies have reported leak rate as low as 5% with stapled technique. However, the stricture rate is higher in the stapled group. There is no randomized study comparing hand-sewn anastomosis with side-to-side stapled anastomosis. Hence, the investigators planned a randomized trial comparing the anastomotic sequelae after hand-sewn anastomosis with stapled anastomosis in the neck.

early laryngeal cancer is a well known field with great controversy in treatment. two options are available in treatment of patients the first one is partial laryngectomy and the second one is radiotherapy.one of major concern of patients have been the quality of voice as part of quality of life ,so we design this clinical randomised trial to answer the priority of each options.

early laryngeal cancer is a well known field with great controversy in treatment. two options are available in treatment of patients the first one is partial laryngectomy and the second one is radiotherapy.one of major concern of patients have been the quality of voice ,so we design this trial to answer the priority of each options.