bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic Repair of Large Skull Base Defects after Powered Sinus Surgery
Authors: Church Christopher A. , Chiu Alexander G. , Vaughan Winston C.
Published: September 2003

OBJECTIVES

To evaluate the management of patients with large skull base defects (> 2 cm) and intracranial injury caused by powered endoscopic sinus surgery.

STUDY DESIGN AND SETTING

All patients treated for postendoscopic sinus surgery skull base injury over a 4‐year period were reviewed.

RESULTS

Three patients with skull base defects greater than 2 cm in size and associated intracranial injury from powered ESS were identified. All patients presented with active cerebrospinal fluid leaks. CT scans showed intracranial injury and pathology reports revealed brain tissue removal. Using image‐guided endoscopic techniques, all defects were addressed with multilayer repair. Closure was achieved in all patients on the first attempt, with an average follow‐up of 27 months.

CONCLUSIONS

The use of powered instrumentation along the skull base can be dangerous and can result in extensive skull base defects with associated loss of dura and gray matter. Large ethmoid roof defects and significant intracranial injury, however, are not absolute contraindications to endoscopic repair.
The Role of Leukotrienes in Nasal Allergy
Authors: Haberal Ilknur , Corey Jacquelynne P.
Published: September 2003

OBJECTIVE

This review focuses on the role of cysteinyl leukotrienes (cysLTs) in nasal allergy. The purpose was to provide knowledge of the role of cysLTs in the pathophysiology of nasal allergy and the role of antileukotrienes in the treatment of nasal allergies.

MATERIALS AND METHODS

We conducted a literature review.

RESULTS

The proinflammatory effects of cysLTs have been well described in asthma. Antileukotrienes have proved to be an effective anti‐inflammatory treatment for asthma patients. Similar to pathogenesis of asthma, cysLTs exert potent inflammatory effects in the upper airways and play a role in the pathogenesis of allergic rhinitis and other nasal allergies.

CONCLUSION

Antileukotriene treatment appears to be beneficial in nasal allergies. Allergic rhinitis is a complex, IgE‐mediated inflammatory disease of the upper airways. It is the most common allergic disease, occurring in 10% to 30% of adults and up to 30% of children. It may be perennial or seasonal. Sneezing, itching, watery rhinorrhea, and nasal obstruction are classic symptoms. It may impair cognition, school/work performance and productivity, behavior, mood, and quality of life. On physical examination, clear secretions, nasal congestion, pink‐bluish nasal mucosa, the allergic salute, and allergic shiners may be detected. Allergic rhinitis is a common comorbid condition with asthma, sinusitis, otitis media, nasal polyposis, and respiratory infections.
Posterior Cartilage Graft in Single‐Stage Laryngotracheal Reconstruction
Authors: Younis Ramzi T. , Lazar Rande H. , Astor Frank
Published: September 2003

PURPOSE

Single‐stage laryngotracheal reconstruction (LTR) has gained popularity during the past decade, but few reports discuss posterior grafting. We assessed the indications, treatment, complications, and outcomes for patients who underwent this procedure.

METHODS

We reviewed the charts of 120 pediatric patients who underwent LTR at LeBonheur Children's Medical Center or the University of Mississippi Medical Center between January 1992 and September 2000. We identified and evaluated those who had undergone single‐stage anterior plus posterior cartilage rib graft reconstruction during this period.

RESULTS

Of 120 patients, 56 had anterior graft procedures, and 46 had anterior plus posterior cartilage rib graft reconstruction. The 46 patients included 26 boys and 20 girls (age range, 18 months to 9 years; follow‐up periods, 3 months to 6 years). Twenty‐one of 46 had circumferential grade III stenosis, 14 had grade IV stenosis, 4 had bilateral vocal cord paralysis, 4 had posterior glottic and subglottic stenosis, and 3 had laryngeal cleft. Eleven of 46 patients had previous procedures and required revision LTR. All 46 patients underwent single‐stage reconstruction with temporary stenting using an endotracheal tube for 10 to 24 days; 4 failed required replacement of the tracheotomy tube, and 8 required reintubation after the first extubation. The overall decannulation success rate was 83% (38 of 46).

CONCLUSIONS

LTR is the procedure of choice for the surgical management of subglottic stenosis. Although use of a posterior rib graft is technically demanding and requires extensive experience, good results can be obtained when the guidelines are followed.
The Role of Positron Emission Tomography in the Evaluation of the N‐Positive Neck
Authors: Wax Mark K. , Myers Larry L. , Gona Jayakumari M. , Husain Syed S. , Nabi Hani A.
Published: September 2003

BACKGROUND

A major prognostic indicator in patients with squamous cell carcinoma of the upper aerodigestive tract is the presence or absence of cervical metastasis. Nodal involvement at different levels affects treatment. Thus identification of the degree of nodal involvement is important. Evaluation of the neck by conventional imaging modalities (computed tomography or magnetic resonance imaging) is not completely accurate. Positron emission tomography (PET) scanning as a dynamic functional assessment may allow detection of multiple metastatic nodes at different levels.

PURPOSE

We sought to compare the effectiveness of PET with pathologic examination for: presence, location, and number of cervical metastases in the clinically N‐positive neck.

SETTING

Tertiary care academic facility.

MATERIALS AND METHODS

From 1994 to 1997, 15 patients with clinically N‐positive necks who had preoperative PET scans underwent 23 neck dissections. PET scans were correlated with the pathologic findings of the neck dissections in determining the ability to correctly identify the number and level(s) of nodal disease.

RESULTS

When determining identification of the level of disease, PET demonstrated sensitivity of 81%; specificity, 99%; positive predictive value, 97%; negative predictive value, 90%; and accuracy, 92%. When evaluating the ability to correctly predict neck stage, PET demonstrated sensitivity of 86%, positive predictive value of 100%, and accuracy of 80% compared with clinical examination with sensitivity of 53% and accuracy of 53%.

CONCLUSION

PET accurately identified disease in the N‐positive neck. Its ability to identify multiple level disease may allow it to help predict the selectivity of neck dissection in the therapeutic protocol.
Reconstruction of Complex Parotidectomy Defects Using the Lateral Arm Free Tissue Transfer
Authors: Teknos Theodoros N. , Nussenbaum Brian , Bradford Carol R. , Prince Mark E. , El‐Kashlan Hussam , Chepeha Douglas B.
Published: September 2003

OBJECTIVES

The study goal was to show that the lateral arm flap is a viable reconstructive option for complex parotidectomy defects.

STUDY DESIGN AND SETTING

We studied a case series at a tertiary care medical center from March 1997 to March 2002. The lateral arm flap was used to reconstruct parotidectomy defects that included a composite resection of adjacent tissue in 30 patients. There were 19 men and 11 women (mean age, 62 years; mean follow‐up, 19 months). The mean flap area was 114 cm2, and the mean flap volume was 172 cm3. The posterior cutaneous nerve of the forearm (PCNF) was used as a facial nerve cable graft in 14 patients. Facial disability outcomes were measured using the Facial Clinimetric Evaluation scale.

RESULTS

The major and minor complication rates with use of this reconstructive approach were low: 16.7% (5 of 30) and 26.7% (8 of 30), respectively. Donor site morbidity was minimal, with no patient having a major donor site complication and 23.3% (7 of 30) having minor complications. Functional recovery of the facial nerve occurred in 6 of 8 evaluable patients who underwent facial nerve grafting using the PCNF. Controlling for degree of facial nerve paralysis, Facial Clinimetric Evaluation scale scores of our patients were not statistically different than those of a historic population with a facial paralysis and no surgical defect.

CONCLUSIONS

The lateral arm free flap effectively restores facial appearance when used for reconstruction of complex parotidectomy defects. The PCNF, a nerve harvested with the lateral arm flap, can be used as a facial nerve cable graft with a high rate of success.

SIGNIFICANCE

The lateral arm flap is successful as a single donor site for reconstructing facial contour and the facial nerve after major ablative defects in the parotid region.
Intra-Articular Fractures of the Distal Radius: A Prospective Randomised Controlled Trial Comparing Static Bridging and Dynamic Non-Bridging External Fixation
Authors: KRISHNAN J. , WIGG A. E. R. , WALKER R. W. , SLAVOTINEK J.
Published: September 2003

This prospective randomized trial compared a non-bridging external fixator with a bridging external fixator system for the treatment of severe comminuted intra-articular fractures of the distal radius. The results did not demonstrate a statistically significant difference in the radiological and clinical outcomes achieved with these two treatments.
Incidence of Osteoarthritis in the Scapho-Trapezial Joint After Herbert Screw Fixation of the Scaphoid
Authors: KEHOE N. J. S. , HACKNEY R. G. , BARTON N. J.
Published: September 2003

Twenty patients treated with a Herbert screw for scaphoid fractures (acute or non-union) were reviewed and X-rayed 5–10 years later to assess whether there were degenerative changes in the scapho-trapezial joint due to insertion of the screw. Six had some irregularity in the lateral part of that joint, three of which followed backing-out of the screw. Two others were described as showing irregularity all round the scaphoid but, apart from these, no radiological abnormalities were seen in the central or ulnar part of the scapho-trapezial joint, or on the proximal tip of the scaphoid.
Prevalence and Distribution of Hand Fractures
Authors: VAN ONSELEN E. B. H. , KARIM R. B. , HAGE J. JORIS , RITT M. J. P. F.
Published: September 2003

A retrospective survey of the medical charts of all 36,518 patients attending the Accident and Emergency Department of the VU University Medical Centre, in Amsterdam, from January 1 to December 31, 1996 was performed. Of these, 4303 sustained one or more fractures, and hand fractures accounted for 19% of all fractures. Patients with hand fractures were typically men aged between 15 and 35 years. The right hand was involved as often as the left. Most of the hand fractures involved the metacarpals but, as a group of bones, the combined phalanges were most commonly fractured. The little finger ray was most commonly injured of the hand. We found no seasonal variability in the incidence of hand fractures.
Coronal Fractures of the Proximal Scaphoid: The Proximal Ring Sign
Authors: HERZBERG G. , FORISSIER D. , FALAISE C.
Published: September 2003

We present two coronal fractures of the proximal scaphoid which were both missed in the acute stage as interpretation of initial radiographs was difficult. In both cases, recognition of the so-called “Proximal Ring Sign” on the PA ulnar deviation radiographs may have helped diagnosis. CT scans were necessary to fully demonstrate the fractures. Open reduction and internal fixation, performed 2 and 4 months after the injury, resulted in union in both cases.
Five-Year Results of a New Total Replacement Prosthesis for the Finger Metacarpo-phalangeal Joints
Authors: HARRIS D. , DIAS J. J.
Published: September 2003

An unconstrained surface metacarpophalangeal joint replacement was developed with metal metacarpal and polyethylene phalangeal components, fixed by uncemented finned polyethylene plugs which allowed some metacarpal component motion. Clinical and radiological results in 13 joints in eight patients are presented after 5 years. One infection required revision at 3 months. There were no further complications. At final review there were no implant failures. Two of 13 joints showed lucency around the phalangeal component and one showed 2 mm subsidence of the metacarpal component. No other adverse radiological features were observed. Seven patients had no pain and one had minor discomfort. Joint movement had improved from an arc of 27° to 60° and disability, assessed using the P.E.M. questionnaire, had improved from 77% to 9%.
Embedded Cross-Stitch Suture: An Alternative to Current Cross-Stitch Peripheral Suture
Authors: WANG B. , TANG J. B.
Published: September 2003

The cross-stitch peripheral suture has good strength, but the large amount of exposed suture on the tendon surface has restricted its clinical usage. We report a method of embedded cross-stitch that incorporates cross-stitches into peripheral sutures and reduces the amount of exposed suture on the tendon surface. Thirty-three fresh pig flexor tendons were divided equally into three groups and repaired with cross-stitch, embedded cross-stitch, or modified Halsted sutures. The tendons were tested in an Instron tensile machine to assess the mechanical performance of these repairs. With an identical number of strands across the repair site, the gap formation and ultimate forces of the embedded cross-stitch method were statistically greater than those of the cross-stitch and modified Halsted methods. The embedded cross-stitch method also had significantly greater stiffness and energy to failure than the cross-stitch method. The embedded cross-stitch method, with little suture exposure on the tendon and sufficient strength, presents an alternative to the current cross-stitch peripheral repair.
Neurophysiological Recovery After Open Carpal Tunnel Decompression: Comparison of Simple Decompression and Decompression with Epineurotomy
Authors: BORISCH N. , HAUSSMANN P.
Published: September 2003

Two hundred and seventy-three patients with carpal tunnel syndrome without advanced neurophysiological changes (distal motor latency below 11 ms) were randomized to treatment by open carpal tunnel release with, or without, epineurotomy. Patients were examined clinically and by nerve conduction studies preoperatively and at 3, 6 and 12 months postoperatively. We found no statistically significant difference between simple decompression and decompression combined with epineurotomy with regard to either the clinical or the neurophysiological outcome.
Altered Cbfal expression and biomineralization in an osteosarcoma cell line
Authors: Perinpanayagam H. , Schneider G. , Holtman K. , Zaharias R. , Stanford C.
Published: September 2003

Osteoblast differentiation and expression are regulated by Cbfal transcription factors. Recent evidence suggests that Cbfal may also regulate bone mineralization. The purpose of this study was to characterize Cbfal expression in relation to mineralization in rat UMR106‐01 osteoblastic cell cultures. UMR106‐01 BSP cultures consistently form bone‐like mineral, whereas the UI subclone mineralize gradually. BSP and UI cultures were grown for 48 h and then treated with β‐glycerophosphate. BSP cultures had alizarin red stained calcifications and mineral‐like deposits within 24 h of phosphate. Atomic absorption spectroscopy measured significantly (P < 0.0001) more calcium in the phosphate‐treated BSP cultures than in the UI. Cbfal message was detected in the BSP and UI cultures, but the Cbfal N‐terminal isoform was deficient in UI and appeared to be up‐regulated in the phosphate‐treated BSP cultures. Cbfal protein levels were also reduced in the UI. DNA sequence from the RT‐PCR products was utilized to design Taqman Real‐time RT‐PCR reagents. Quantitative Real‐time RT‐PCR analysis showed that Cbfal mRNA levels relative to endogenous 18 s rRNA were lower in the slower mineralizing UI cultures. Furthermore, the Cbfal N‐terminal isoform mRNA levels were significantly (P < 0.001) lower in the slower mineralizing cultures. Transfection with Cbfal or isoform antisense caused a significant (P < 0.001) reduction in mineralization. Therefore, Cbfal expression may be associated with bone‐like mineral formation in rat UMR106‐01 osteoblastic cell cultures. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Spring–summer climatological circulation in the upper layer in the region of Cape St. Vincent, Southwest Portugal
Authors: Sánchez Ricardo F. , Relvas Paulo
Published: September 2003

Geostrophic transport and hydrographic measurements derived from a historical database (1900–1998) were used to study the spring–summer mean circulation in the upper layer south and west of Cape St. Vincent, Southwest (SW) Portugal. The larger-scale circulation scheme is forced by equatorward winds from May to September, when the Iberian coastal transition zone (CTZ) is dominated by a generalized upwelling of cold, low-salinity water. A partially separated surface jet intensified at the shelf break conveys ∼1 Sv of upwelled water equatorward parallel to the bathymetry, while offshore a poleward flow transports ∼0.4–0.6 Sv of upwelled water. Although alongshore transports dominate the circulation pattern of the upper layers, cross-shore transports are significant at the climatological scale. Anticyclonic circulation with an exchange of ∼0.5 Sv from the equatorward jet to the offshore poleward flow and the partial re-circulation further north, back into the equatorward flow are discussed. A coherent, cyclonic re-circulation pattern inshore of the upwelling jet is also speculated. From these results the shelf break is considered a climatological border at both sides of which two major re-circulation cells occur. The climatological equatorward flow has offshore protrusions, interpreted as recurrent episodes of major contortions of the upwelling flow. These features bring about considerable “cross-shelf flow” re-circulation reaching up to 50% of the main flow. The most significant exchanges are found to be associated with major changes of orientation of the coastline. Off Cape St. Vincent the upwelling front stretches to both west and south and contributes to the cross-shelf re-circulations. Additionally, convergence of the upwelling flow and a branch of the Azores current, with associated re-circulation is found diagonally from the cape. On the southern coast the upwelling jet is seen to meander offshore in the vicinity of Cape St. Maria. Individual synoptic cruise data showed agreement with the climatological circulation features. We conclude that these oceanographic features leave an imprint on the climatic circulation in spite of the “smoothing out” of recurrent events over the spring–summer period of the years of 1900–1998.
Bimodal regulatory effect of melittin and phospholipase A2‐activating protein on human type II secretory phospholipase A2
Authors: Koumanov K. , Momchilova A. , Wolf C.
Published: September 2003

Melittin and phospholipase A2‐activating protein (PLAP) are known as efficient activators of secretory phospholipase A2(sPLA2) types I, II, and III when phospholipid liposomes are used as substrate. The present study demonstrates that both peptides can either inhibit or activate sPLA2depending on the peptide/phospholipid ratio when erythrocyte membranes serve as a biologically relevant substrate. Low concentrations of melittin and PLAP were observed to inhibit sPLA2–triggered release of fatty acids from erythrocyte membranes. The inhibition was reversed at melittin concentrations above 1 μM. PLAP‐induced inhibition of sPLA2persisted steadily throughout the used concentration range (0–150 nM). The two peptides induced a dose‐dependent activation of sPLA2at low concentrations, followed by inhibition when model membranes were used as substrate. This opposite modulatory effect on biological membranes and model membranes is discussed with respect to different mechanisms the interaction of the regulatory peptides with the enzyme molecules and the substrate vesicles.
Prophylactic tolperisone for post‐exercise muscle soreness causes reduced isometric force—adouble‐blind randomized crossover control study
Authors: Bajaj Prem , Arendt‐Nielsen Lars , Madeleine Pascal , Svensson Peter
Published: September 2003

The role of tolperisone hydrochloride, a centrally acting muscle relaxant in relieving painful muscle spasm is recently being discussed. The present study hypothesizes that the prophylactic use of tolperisone hydrochloride may effectively relieve post‐exercise muscle soreness, based on the spasm theory of exercise pain. Twenty male volunteers, aged 25.2±0.82 years (mean±SEM) participated in 10 sessions in which they received oral treatment with placebo or the centrally acting muscle relaxant tolperisone hydrochloride (150 mg) three times daily for 8 days, in randomized crossover double‐blind design. Time course assessments were made for pressure pain threshold, Likert's pain score (0–5), pain areas, range of abduction, isometric force, and electromyography (EMG) root mean square (RMS) during maximum voluntary isometric force on day 1 and 6, immediately after an eccentric exercise of first dorsal interosseous muscle, and 24 and 48 h after the exercise. Treatment with placebo or tolperisone hydrochloride was initiated immediately after the assessments on the first day baseline assessments. On the sixth day baseline investigations were repeated and then the subjects performed six bouts of standardized intense eccentric exercise of first dorsal interosseous muscle for provocation of post‐exercise muscle soreness (PEMS). Perceived intensity of warmth, tiredness, soreness and pain during the exercise bouts were recorded on a 10 cm visual analogue pain scale. VAS scores and pressure pain thresholds did not differ between tolperisone and placebo treatment. All VAS scores increased during the exercise bouts 2, 3, 4, 5 and 6 as compared to bout 1. Increased pain scores and pain areas were reported immediately after, 24 and 48 h after exercise. Pressure pain thresholds were reduced at 24 and 48 h after the exercise in the exercised hand. Range of abduction of the index finger was reduced immediately after the exercise and was still reduced at 24 h as compared to the non‐exercised hand. The EMG RMS amplitude was also reduced immediately after the exercise, but was increased at 24 and 48 h. Isometric force was reduced immediately after the exercise as compared to days 1, 6, and the 24 and 48 h post‐exercise assessments with a greater reduction following the tolperisone hydrochloride treatment and the reduction was more in tolperisone group as compared to the placebo group. The results suggest, that the prophylactic intake of tolperisone hydrochloride provides no relief to pain in course of post‐exercise muscle soreness but results in reduction in isometric force.
Measures of anxiety: is there a difference in their ability to predict functioning at three‐month follow‐up among pain patients?
Authors: Hadjistavropoulos Heather D , Asmundson Gordon J.G , Kowalyk Kristine M
Published: September 2003

Independent investigators have found that pain is related to health anxiety, trait anxiety, pain‐related anxiety, and anxiety sensitivity. To date, the relationship among these anxiety‐related constructs has not been studied directly and little is known about their relative ability to predict adjustment to pain over time. This paper presents longitudinal data from measures given to 227 musculoskeletal pain patients. Patients were asked at the time of their first visit (T1) to a physiotherapy clinic to complete a questionnaire package including measures of these different forms of anxiety as well as pain severity, disability, negative affect, and perceived control. Approximately 3 months later (T2), 50% of patients responded to these same questionnaires. Results showed that correlations among the anxiety measures at T1 ranged from 0.35 to 0.56. Using multiple regression analyses, measures of T1 anxiety were each examined for their ability to predict unique variance in disability, negative affect, and perceptions of control measured at T1 and T2. At T1, after controlling for pain severity and other measures of anxiety, pain‐related anxiety uniquely predicted both disability and negative affect, trait anxiety uniquely predicted negative affect and perceptions of control, and anxiety sensitivity uniquely predicted negative affect. At T2, after controlling for pain severity, other measures of anxiety and each respective measure of functioning at T1, health anxiety uniquely predicted disability and negative affect, although anxiety sensitivity also uniquely contributed to the prediction of negative affect. It is concluded that the importance of various forms of anxiety is dependent on the timeframe and outcome examined. Clinical implications of the findings as well as directions for future research are discussed.
Key role of the dorsal root ganglion in neuropathic tactile hypersensibility
Authors: Sukhotinsky Inna , Ben‐Dor Efrat , Raber Pnina , Devor Marshall
Published: September 2003

Cutting spinal nerves just distal to the dorsal root ganglion (DRG) triggers, with rapid onset, massive spontaneous ectopic discharge in axotomized afferent A‐neurons, and at the same time induces tactile allodynia in the partially denervated hindlimb. We show that secondary transection of the dorsal root (rhizotomy) of the axotomized DRG, or suppression of the ectopia with topically applied local anesthetics, eliminates or attenuates the allodynia. Dorsal rhizotomy alone does not trigger allodynia. These observations support the hypothesis that ectopic firing in DRG A‐neurons induces central sensitization which leads to tactile allodynia. The question of how activity in afferent A‐neurons, which are not normally nociceptive, might induce allodynia is discussed in light of the current literature.
Peripheral effects of needle stimulation (acupuncture) on skin and muscle blood flow in fibromyalgia
Authors: Sandberg Margareta , Lindberg Lars‐Göran , Gerdle Björn
Published: September 2003

Acupuncture has become a widely used treatment modality in various musculoskeletal pain conditions. Acupuncture is also shown to enhance blood flow and recovery in surgical flaps. The mechanisms behind the effect on blood flow were suggested to rely on vasoactive substances, such as calcitonin gene‐related peptide, released from nociceptors by the needle stimulation. In a previous study on healthy subjects, one needle stimulation into the anterior tibial muscle was shown to increase both skin and muscle blood flow. The aim of this study was to examine the effect of needle stimulation on local blood flow in the anterior tibial muscle and overlying skin in patients suffering from a widespread chronic pain condition. Fifteen patients with fibromyalgia (FM) participated in the study. Two modes of needling, deep muscle stimulation and subcutaneous needle insertion were performed at the upper anterior aspect of the tibia, i.e., in an area without focal pathology or ongoing pain in these patients. Blood flow changes were assessed non‐invasively by photoplethysmography (PPG). The results of the present study were partly similar to those earlier found at a corresponding site in healthy female subjects, i.e., deep muscle stimulation resulted in larger increase in skin blood flow (mean (SE)): 62.4% (13.0) and muscle blood flow: 93.1% (18.6), compared to baseline, than did subcutaneous insertion (mean (SE) skin blood flow increase: 26.4% (6.2); muscle blood flow increase: 46.1% (10.2)). However, in FM patients subcutaneous needle insertion was followed by a significant increase in both skin and muscle blood flow, in contrast to findings in healthy subjects where no significant blood flow increase was found following the subcutaneous needling. The different results of subcutaneous needling between the groups (skin blood flow: p=0.008; muscle blood flow: p=0.027) may be related to a greater sensitivity to pain and other somatosensory input in FM.
Increased exercise ejection fraction and reversed remodeling after long‐term treatment with metoprolol in congestive heart failure: a randomized, stratified, double‐blind, placebo‐controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy
Authors: Waagstein F. , Strömblad O. , Andersson B. , Böhm M. , Darius M. , Delius W. , Goss F. , Osterziel K.J. , Sigmund M. , Trenkwalder S.‐P. , Wahlqvist I.
Published: September 2003

Background:

the effects of long‐term administration of β‐blockers on left ventricular (LV) function during exercise in patients with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM) are controversial.

Patients and methods:

patients with stable congestive heart failure (CHF) (New York heart association [NYHA] class II and III) and ejection fraction (EF) ≤0.40 were randomized to metoprolol, 50 mg t.i.d. or placebo for 6 months. Patients were divided into two groups: ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM). The mean EF was 0.29 in both groups and 92% were taking angiotensin‐converting enzyme (ACE) inhibitors. In the IHD group, 84% had suffered a myocardial infarction (MI) and 64% had undergone revascularization at least 6 months before the study. LV volumes were measured by equilibrium radionuclide angiography. Mitral regurgitation was assessed by Doppler echocardiography. All values are changes for metoprolol subtracted by changes for placebo.

Results:

metoprolol improved LV function markedly both at rest and during sub‐maximal exercise in both groups. The mean increase in EF was 0.069 at rest (P<0.001) and 0.078 during submaximal exercise (P<0.001). LV end‐diastolic volume decreased by 22 ml at rest (P=0.006) and by 15 ml during exercise (P=0.006). LV end‐systolic volume decreased by 23 ml both at rest (P=0.001) and during exercise (P=0.004). Exercise time increased by 39 s (P=0.08). In the metoprolol group, mitral regurgitation decreased (P=0.0026) and only one patient developed atrial fibrillation vs. eight in the placebo group (P=0.01).

Conclusion:

metoprolol improves EF both at rest and during submaximal exercise and prevents LV dilatation in mild to moderate CHF due to IHD or DCM.
Frequency adaptation efficiency of spread spectrum communications under narrowband interference
Authors: Goot R. E. , Gavan J.
Published: September 2003

We investigate a new possibility of frequency adaptation for spread spectrum communication systems. A special index is introduced to characterize the adaptation gain referring to the nonadaptive case. An existence of frequency band limit is developed for the allocated frequency band for possible frequency maneuver. The investigation method can be adapted both to direct sequence and frequency hopping spread spectrum techniques. In the paper only the narrowband interference case is treated
Application of stochastic simulation to CO2 flux from soil: Mapping and quantification of gas release
Authors: Cardellini C. , Chiodini G. , Frondini F.
Published: September 2003

Conditional sequential Gaussian simulations (sGs) have been applied for the first time to the study of soil diffuse degassing from different volcanic and nonvolcanic systems. The application regards five data sets of soil CO2 fluxes measured with the accumulation chamber methodology at the volcanic areas of Solfatara of Pozzuoli (Italy), Vesuvio cone (Italy), Nisyros (Greece), and Horseshoe Lake (California) and at the nonvolcanic degassing area of Poggio dell'Olivo (Italy). The sGs algorithm was used to generate 100 realizations of CO2 flux for each area. Probabilistic summaries of these simulations, together with the information given by probability plots, were used (1) to draw maps of the probability that CO2 fluxes exceed thresholds specific for a background flux, i.e., to define the probable extension of the degassing structures, (2) to calculate the total CO2 output, and (3) to quantify the uncertainty of the estimation. The results show that the sGs is a suitable tool to model soil diffuse degassing, producing realistic images of the distribution of the CO2 fluxes that honor the histogram and variogram of the original data. Moreover, the relation between the sample design and the uncertainty of estimation was investigated leading to an empirical relation between uncertainty and the sampling density that can be useful for the planning of future CO2 flux surveys.
Emission from international sea transportation and environmental impact
Authors: Endresen Øyvind , Sørgård Eirik , Sundet Jostein K. , Dalsøren Stig B. , Isaksen Ivar S. A. , Berglen Tore F. , Gravir Gjermund
Published: September 2003

Emission generated by the international merchant fleet has been suggested to represent a significant contribution to the global anthropogenic emissions. To analyze the impacts of these emissions, we present detailed model studies of the changes in atmospheric composition of pollutants and greenhouse compounds due to emissions from cargo and passenger ships in international trade. Global emission inventories of NOx, SO2, CO, CO2, and volatile organic compounds (VOC) are developed by a bottom‐up approach combining ship‐type specific engine emission modeling, oil cargo VOC vapor modeling, alternative global distribution methods, and ship operation data. Calculated bunker fuel consumption is found in agreement with international sales statistics. The Automated Mutual‐assistance Vessel Rescue system (AMVER) data set is found to best reflect the distributions of cargo ships in international trade. A method based on the relative reporting frequency weighted by the ship size for each vessel type is recommended. We have exploited this modeled ship emissions inventory to estimate perturbations of the global distribution of ozone, methane, sulfate, and nitrogen compounds using a global 3‐D chemical transport model with interactive ozone and sulfate chemistry. Ozone perturbations are highly nonlinear, being most efficient in regions of low background pollution. Different data sets (e.g., AMVER, The Comprehensive Ocean‐Atmosphere Data Set (COADS)) lead to highly different regional perturbations. A maximum ozone perturbation of approximately 12 ppbv is obtained in the North Atlantic and in the North Pacific during summer months. Global average sulfate loading increases with 2.9%, while the increase is significantly larger over parts of western Europe (up to 8%). In contrast to the AMVER data, the COADS data give particularly large enhancements over the North Atlantic. Ship emissions reduce methane lifetime by approximately 5%. CO2 and O3 give positive radiative forcing (RF), and CH4 and sulfate give negative forcing. The total RF is small (0.01–0.02 W/m2) and connected with large uncertainties. Increase in acidification is 3–10% in certain coastal areas. The approach presented here is clearly useful for characterizing the present impact of ship emission and will be valuable for assessing the potential effect of various emission‐control options.
Parallel analysis of transcript and metabolic profiles: a new approach in systems biology
Authors: Urbanczyk‐Wochniak Ewa , Luedemann Alexander , Kopka Joachim , Selbig Joachim , Roessner‐Tunali Ute , Willmitzer Lothar , Fernie Alisdair R
Published: September 2003

The past few years in the medical and biological sciences have been characterized by the advent of systems biology. However, despite the well‐known connectivity between the molecules described by transcriptomic, proteomic and metabolomic approaches, few studies have tried to correlate parameters across the various levels of systemic description. When comparing the discriminatory power of metabolic and RNA profiling to distinguish between different potato tuber systems, using the techniques described here suggests that metabolic profiling has a higher resolution than expression profiling. When applying pairwise transcript–metabolite correlation analyses, 571 of the 26,616 possible pairs showed significant correlation, most of which was novel and included several strong correlations to nutritionally important metabolites. We believe this approach to be of high potential value in the identification of candidate genes for modifying the metabolite content of biological systems.
Levofloxacin‐based triple therapy vs. quadruple therapy in second‐line Helicobacter pylori treatment: a randomized trial
Authors: Nista E. C. , Candelli M. , Cremonini F. , Cazzato I. A. , Di Caro S. , Gabrielli M. , Santarelli L. , Zocco M. A. , Ojetti V. , Carloni E. , Cammarota G. , Gasbarrini G. , Gasbarrini A.
Published: September 2003

Background : Levofloxacin has been shown to be effective in Helicobacter pylori eradication. Two 10‐day levofloxacin‐based triple therapies were compared with standard 7‐ and 14‐day quadruple regimens in second‐line treatment.

Methods : Two hundred and eighty consecutive patients who failed to respond to standard triple therapy (clarithromycin, amoxicillin, rabeprazole) were randomly assigned to four groups: (1) levofloxacin 500 mg o.d., amoxicillin 1 g b.d., rabeprazole 20 mg b.d. for 10 days (LAR, n = 70); (2) levofloxacin 500 mg o.d., tinidazole 500 mg b.d., rabeprazole 20 mg b.d. for 10 days (LTR, n = 70); (3) tetracycline 500 mg q.d.s., metronidazole 500 mg t.d.s., bismuth salt 120 mg q.d.s., rabeprazole 20 mg b.d. for 7 days (7TMBR, n = 70); and (4) for 14 days (14TMBR, n = 70). Helicobacter pylori status and side‐effects were assessed 6 weeks after treatment.

Results : The eradication rate was 94% in the LAR group and 90% in the LTR group in both intention‐to‐treat and per protocol analyses. Helicobacter pylori eradication was achieved in 63 and 69% of the 7TMBR group and in 69 and 80% of the 14TMBR group in intention‐to‐treat and per protocol analysis, respectively. Side‐effects were significantly lower in the LAR and LTR groups than in the 14TMBR group.

Conclusion : Ten‐day levofloxacin‐based therapies are better than standard quadruple regimens as second‐line option for H. pylori eradication.
Type 1 diabetes mellitus in patients with chronic hepatitis C before and after interferon therapy
Authors: Fabris P. , Floreani A. , Tositti G. , Vergani D. , De Lalla F. , Betterle C.
Published: September 2003

Type 1 diabetes mellitus is the result of an autoimmune process characterized by pancreatic beta cell destruction. It has been reported that chronic hepatitis C infection is associated with type 2 diabetes mellitus, but not with type 1. Although the prevalence of markers of pancreatic autoimmunity in hepatitis C virus‐positive patients is not significantly different to that reported in the general population, it increases during alpha‐interferon therapy from 3 to 7%, probably due to the immunostimulatory effects of this cytokine. To date, 31 case reports of type 1 diabetes mellitus related to interferon treatment have been published. Type 1 diabetes mellitus occurs more frequently in patients treated for chronic hepatitis C than for other conditions and is irreversible in most cases. In 50% of these patients, markers of pancreatic autoimmunity predated treatment, the majority of cases having a genetic predisposition. Thus, in predisposed individuals, alpha‐interferon can either induce or accelerate a diabetogenic process already underway. We suggest that islet cell autoantibodies and glutamic acid decarboxylase autoantibodies should be investigated before and during interferon treatment in order to identify subjects at high risk of developing type 1 diabetes mellitus.
Sarco‐endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitors identify a novel calcium pool in the central nervous system
Authors: Watson William D. , Facchina Stephen L. , Grimaldi Maurizio , Verma Ajay
Published: September 2003

Ca2+ uptake into the endoplasmic reticulum (ER) is mediated by Ca2+ ATPase isoforms, which are all selectively inhibited by nanomolar concentrations of thapsigargin. Using ATP/Mg2+‐dependent 45Ca2+ transport in rat brain microsomes, tissue sections, and permeabilized cells, as well as Ca2+ imaging in living cells we distinguish two ER Ca2+ pools in the rat CNS. Nanomolar levels of thapsigargin blocked one component of brain microsomal 45Ca2+ transport, which we designate as the thapsigargin‐sensitive pool (TG‐S). The remaining component was only inhibited by micromolar thapsigargin, and thus designated as thapsigargin resistant (TG‐R). Ca2+ ATPase and [32P]phosphoenzyme assays also distinguished activities with differential sensitivities to thapsigargin. The TG‐R Ca2+ uptake displayed unique anion permeabilities, was inhibited by vanadate, but was unaffected by sulfhydryl reduction. Ca2+ sequestered into the TG‐R pool could not be released by inositol‐1,4,5‐trisphosphate, caffeine, or cyclic ADP‐ribose. The TG‐R Ca2+ pool had a unique anatomical distribution in the brain, with selective enrichment in brainstem and spinal cord structures. Cell lines that expressed high levels of the TG‐R pool required micromolar concentrations of thapsigargin to effectively raise cytoplasmic Ca2+ levels. TG‐R Ca2+ accumulation represents a distinct Ca2+ buffering pool in specific CNS regions with unique pharmacological sensitivities and anatomical distributions.
SER‐7b, a constitutively active Gαs coupled 5‐HT7‐like receptor expressed in the Caenorhabditis elegans M4 pharyngeal motorneuron
Authors: Hobson Robert J. , Geng Jinming , Gray Anjali D. , Komuniecki Richard W.
Published: September 2003

Serotonin plays a key role in the regulation of pharyngeal pumping in nematodes. We have isolated a Caenorhabditis elegans cDNA (C09B7.1b, ser‐7b) with greatest identity to the 5‐HT7 receptor family. Membranes from COS‐7 cells expressing SER‐7b exhibit saturable [3H]‐LSD binding (Kd = 45 nm) that is inhibited by serotonin (5‐HT) and tryptamine, but not by other physiological biogenic amines. Expression of SER‐7b in COS‐7 cells results in dramatic increase in basal cAMP levels over untransfected cells that is dependent on expression level. 5‐HT further elevates cAMP levels in a dose‐dependent manner (pEC50 = 7.5 ± 0.5). Mammalian 5‐HT7 receptor inverse agonists reduce constitutive activity, with methiothepin the most potent (pIC50 = 7.8 ± 0.1). Ser‐7::GFP transcriptional fusions reveal that SER‐7b appears to be expressed solely in the M4 pharyngeal motorneuron after hatching. This is the first report of a Gαs coupled biogenic amine receptor in nematodes and the localization of SER‐7b in the M4 pharyngeal motorneuron suggests that SER‐7b may play a role in the regulation of pharyngeal pumping.
The hemicholinium‐3 sensitive high affinity choline transporter is internalized by clathrin‐mediated endocytosis and is present in endosomes and synaptic vesicles
Authors: Ribeiro F. M. , Alves‐Silva J. , Volknandt W. , Martins‐Silva C. , Mahmud H. , Wilhelm A. , Gomez M. V. , Rylett R. J. , Ferguson S. S. G. , Prado V. F. , Prado M. A. M.
Published: September 2003

Synthesis of acetylcholine depends on the plasma membrane uptake of choline by a high affinity choline transporter (CHT1). Choline uptake is regulated by nerve impulses and trafficking of an intracellular pool of CHT1 to the plasma membrane may be important for this regulation. We have generated a hemagglutinin (HA) epitope tagged CHT1 to investigate the organelles involved with intracellular trafficking of this protein. Expression of CHT1‐HA in HEK 293 cells establishes Na+‐dependent, hemicholinium‐3 sensitive high‐affinity choline transport activity. Confocal microscopy reveals that CHT1‐HA is found predominantly in intracellular organelles in three different cell lines. Importantly, CHT1‐HA seems to be continuously cycling between the plasma membrane and endocytic organelles via a constitutive clathrin‐mediated endocytic pathway. In a neuronal cell line, CHT1‐HA colocalizes with the early endocytic marker green fluorescent protein (GFP)‐Rab 5 and with two markers of synaptic‐like vesicles, VAMP‐myc and GFP‐VAChT, suggesting that in cultured cells CHT1 is present mainly in organelles of endocytic origin. Subcellular fractionation and immunoisolation of organelles from rat brain indicate that CHT1 is present in synaptic vesicles. We propose that intracellular CHT1 can be recruited during stimulation to increase choline uptake in nerve terminals.
The amyloid precursor protein protects PC12 cells against endoplasmic reticulum stress‐induced apoptosis
Authors: Kögel Donat , Schomburg Robert , Schürmann Tina , Reimertz Claus , König Hans‐Georg , Poppe Monika , Eckert Anne , Müller Walter E. , Prehn Jochen H. M.
Published: September 2003

Endoplasmic reticulum (ER) stress is believed to play an important role in neurodegenerative disorders such as Alzheimer's disease. In the present study, we investigated the effect of the human amyloid precursor protein (APP) on the ER stress response in PC12 cells. Tunicamycin, an inhibitor of N‐glycosylation, rapidly induced the expression of the ER‐resident chaperone Bip/grp78, a known target gene of the unfolded protein response. Prolonged treatment with tunicamycin (≥ 12 h) resulted in the activation of executioner caspases 3 and 7. Interestingly, PC12 cells overexpressing human wild‐type APP (APPwt) showed increased resistance to tunicamycin‐induced apoptosis compared with empty vector‐transfected controls. This neuroprotective effect was significantly diminished in cells expressing the Swedish mutation of APP (KM670/671NL). Similar effects were observed when ER stress was induced with brefeldin A, an inhibitor of ER‐to‐Golgi protein translocation. Of note, APP‐mediated neuroprotection was not associated with altered expression of Bip/grp78 or transcription factor C/EBP homologous protein‐10 (CHOP/GADD153), suggesting that APP acted either downstream or independently of ER‐to‐nucleus signaling. Our data indicate that APP plays an important physiological role in protecting neurons from the consequences of prolonged ER stress, and that APP mutations associated with familial Alzheimer's disease may impair this protective activity.
Sensitivity of binary liquid thermal convection to confinement
Authors: Millour E. , Labrosse G. , Tric E.
Published: September 2003

The stable axisymmetric convective states of a binary liquid enclosed in a vertical cylinder heated from below are exhaustively and accurately identified by pseudo-spectral numerical integration. In order to gain some insight on the influence that nearby boundaries can exert on flow dynamics, three aspect ratios (1/2, 1, and 2), as well as two types of lateral kinematic boundary conditions (either no-slip or free-slip) are investigated. The ranges over which stable quiescent, oscillatory and steady convective states extend and coexist are given. The bifurcations leading to transitions from one branch of solutions to another, as well as those that occur along the oscillatory branch, are analyzed. The most significant effect of varying boundary conditions and aspect ratio involves the route from oscillatory to steady convection. For a given configuration, that route consists of a period doubling cascade followed by chaos, or a subcritical generalized Hopf (or Neimark–Sacker) bifurcation, or a homoclinic bifurcation. The dynamics of thermal convection of enclosed binary mixtures is clearly very sensitive to both boundary conditions and aspect ratio.
Evidence of an inverted temperature gradient during evaporation/condensation of a Lennard-Jones fluid
Authors: Frezzotti Aldo , Grosfils Patrick , Toxvaerd Soeren
Published: September 2003

Molecular dynamics simulations of the Lennard-Jones fluid have been performed to study the vapor flow between two liquid slabs kept at slightly different temperatures. For the first time, direct evidence is found of the onset of inverted gradient temperature profiles in the vapor. The simulations results also show good agreement with a kinetic theory analysis of the vapor phase flow field.