bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of intermittent compression of upper arm veins on forearm vessels in patients with end‐stage renal disease
Authors: Rus Rina R. , Ponikvar Rafael , Kenda Rajko B. , Buturovič‐Ponikvar Jadranka
Published: July 2005

Native arteriovenous fistula is the best vascular access for chronic hemodialysis. Primary and long‐term success depends, in part, on the state of arteries and veins at the time of the operation. The aim of our study was to investigate the effects of intermittent compression of upper arm veins on forearm vessels in patients with terminal renal disease. The study group was composed of 16 chronic hemodialysis patients who performed daily intermittent compression of the upper arm without vascular access by elastic band (Eschmarch). Ten chronic hemodialysis patients were included in the control group, which performed no specific activity. Forearm measurements were obtained at the beginning of the study and 4 and 8 weeks later during the course of intermittent compression of the upper arm veins. The forearm circumference and maximal handgrip strength were measured. The artery measures, including endothelium‐dependent vasodilatation and forearm vein variables, were obtained by ultrasonography measurements. The forearm circumference, maximal handgrip strength, and artery variables, including endothelium‐dependent vasodilatation, remained unchanged. The basal venous diameters (2.29 ± 0.19 mm at the beginning, 2.46 ± 0.19 mm after 4 weeks, and 2.53 ± 0.18 mm after 8 weeks) were significantly increased in the study group. The distensibility of veins was preserved in the study group. There were no significant changes in the control group. Our study demonstrated that daily intermittent compression of the upper arm veins increases the forearm vein diameter and preserves the distensibility of veins in patients with end‐stage renal failure.
Characteristics of heart rate variability entropy and blood pressure during hemodialysis in patients with end‐stage renal disease
Authors: Yamanaka Nozomu , Aoyama Togo , Ikeda Noriaki , Higashihara Masaaki , Kamata Kouju
Published: July 2005

Entropy (ENT) is a newly developed measure of the complexity of heart rate variability (HRV). The aim of this study was to characterize the complexity of HRV in patients with end‐stage renal disease (ESRD) and to find a possible clinical utility. Healthy subjects and patients with ESRD undergoing hemodialysis (HD) were recruited. The HD population consisted of patients with and without diabetes mellitus (DM). An electrocardiogram was recorded before HD, and blood pressure was measured during HD. The coefficients of variation of R‐R intervals, high‐ and low‐frequency components, and ratio of the low‐ to high‐frequency components were measured as variables of HRV. The ENT was used to describe the complexity of HRV. Forty‐six healthy subjects and 27 HD patients participated in this study. The ENT negatively correlated with the duration of DM (p = 0.001), systolic blood pressure (p = 0.003), and mean blood pressure (p = 0.004) before a HD session. ENT in HD patients was lower than that in healthy subjects (p < 0.01). ENT in HD patients with DM was lower than that in HD patients without DM (p < 0.01). The change in systolic blood pressure (ΔSBP) during a HD session showed high correlations to ENT and ultrafiltration rate (UFR) of the dialyzer. The following equation was obtained: ΔSBP = 2.25 × ENT − 2.28 × UFR − 21.27 (R2 = 0.805; p < 0.0001). ENT decreased with uremic and diabetic status. ENT also represents a possible prediction of hypotension during a HD session.
Beyond thrice‐weekly hemodialysis
Authors: Diaz‐Buxo Jose A.
Published: July 2005

The frequency, length, and dose of hemodialysis (HD) have empirically evolved during the past four decades. The relationships among these variables and their influence on clinical outcomes are complex. Despite the lack of controlled studies and the selection bias inherent to cohorts studied with enhanced or intensified HD prescriptions, this review explores the impact of frequency, length, and dose of HD on clinical outcomes. The experiences with frequent HD make a formidable case for frequent therapies. The data show that quotidian regimens are associated with the best biochemical profiles, volume and hypertension control, and nutritional status, but do not provide the evidence for superior survival when compared to long nocturnal thrice‐weekly or every‐other‐day conventional HD. The correlation between frequency and clinical outcomes seems evident, but not likely to be linear. Perhaps the greatest benefits are achieved from the simple avoidance of 48 hr without dialysis. Considering the additional cost and patient involvement with daily dialysis compared to every‐other‐day dialysis, it is logical to include the latter in future controlled studies on the benefits of frequent HD.
The Influence of β‐Adrenergic Agonists and Antagonists on T‐Wave Alternans in Patients with and Without Ventricular Tachyarrhythmia
Authors: KOMIYA NORIHIRO , SETO SINJI , NAKAO KOJIRO , YANO KATSUSUKE
Published: July 2005

Background: T‐wave alternans (TWA) is an important noninvasive measurement of ventricular tachyarrhythmia (VT) and is known to be influenced by the sympathetic nervous system. We examined the correlation between TWA measurement and the sympathetic nervous system in patients with and without VT.

Methods and Results: Thirty‐five patients (28 men, 7 women; mean age, 59 ± 15 years) with tachyarrhythmia were assigned to two groups: VT group (n = 15) and supraventricular tachyarrhythmia (SVT) group (n = 20). Alternans voltage in lead vector magnitude (eVM) was measured during atrial pacing (90, 110 beats/min (bpm)). After eVM was measured at baseline, propranolol was administered, and eVM was measured again. In a subset of 18 patients (10 with VT and 8 with SVT), isoproterenol was administered prior to propranolol infusion. After propranolol infusion, eVM of both the VT and the SVT groups decreased significantly compared to baseline. The changes in absolute value of eVM at 110 bpm after propranolol infusion were greater in the VT group than in the SVT group (−1.3 ± 0.8 μV vs −0.5 ± 0.8 μV, P < 0.05). The eVM values of both the VT and the SVT groups increased after administration of isoproterenol compared to the baseline value. The changes in absolute value and percentile of eVM after isoproterenol infusion were smaller in the VT group than in the SVT group (2.0 ± 1.8 μV vs 3.9 ± 3.5 μV, P < 0.05; 21 ± 18% vs 48 ± 36%, P < 0.05).

Conclusions: The sympathetic nervous system has an influence over microvolt‐level TWA. Administration of a β‐adrenergic antagonist caused a significant decrease in TWA, particularly in the VT group. This may partially explain the mechanism by which adrenergic antagonists inhibit VTs.
Cardiac Resynchronization Through Selective His Bundle Pacing in a Patient with the So‐Called InfraHis Atrioventricular Block
Authors: MORIÑA‐VÁZQUEZ PABLO , BARBA‐PICHARDO RAFAEL , VENEGAS‐GAMERO JOSÉ , HERRERA‐CARRANZA MANUEL
Published: July 2005

We present a case of infraHis AV block in which selective His bundle pacing with His‐ventricular conduction through the conduction system was accomplished. While further investigations are developed, this approach may be an alternative for cardiac resynchronization in cases of difficult coronary sinus access.
“V‐H‐A Pattern” as a Criterion for the Differential Diagnosis of Atypical AV Nodal Reentrant Tachycardia from AV Reciprocating Tachycardia
Authors: OWADA SHINGEN , IWASA ATSUSHI , SASAKI SHINGO , HIGUMA TAKUMI , KIMURA MASAOMI , KOBAYASHI TAKAO , ASHIKAGA KEIICHI , OKUMURA KEN
Published: July 2005

Background: During ventricular extrastimulation, His bundle potential (H) following ventricular (V) and followed by atrial potentials (A), i.e., V‐H‐A, is observed in the His bundle electrogram when ventriculo‐atrial (VA) conduction occurs via the normal conduction system. We examined the diagnostic value of V‐H‐A for atypical form of atrioventricular nodal reentrant tachycardia (AVNRT), which showed the earliest atrial activation site at the posterior paraseptal region during the tachycardia.

Methods: We prospectively examined the response of VA conduction to ventricular extrastimulation during basic drive pacing performed during sinus rhythm in 16 patients with atypical AVNRT masquerading atrioventricular reciprocating tachycardia (AVRT) utilizing a posterior paraseptal accessory pathway and 21 with AVRT utilizing a posterior paraseptal accessory pathway. Long RP' tachycardia with RP'/RR > 0.5 was excluded. The incidences of V‐H‐A and dual AV nodal physiology (DP) were compared between atypical AVNRT and AVRT.

Results: V‐H‐A was demonstrated in all the 16 patients (100%) in atypical AVNRT and in only 1 of the 21 (5%) in AVRT (P < 0.001). DP was demonstrated in 10 patients (63%) in atypical AVNRT and in 4 (19%) in AVRT (P < 0.05). The sensitivity of V‐H‐A for atypical AVNRT was higher than that of DP (P < 0.05). Positive and negative predictive values were 94% and 100%, respectively, for V‐H‐A and 71% and 74%, respectively, for DP.

Conclusions: The appearance of V‐H‐A during ventricular extrastimulation is a simple criterion for differentiating atypical AVNRT masquerading AVRT from AVRT utilizing a posterior paraseptal accessory pathway.
Characteristics and Relevance of Clustering Ventricular Arrhythmias in Defibrillator Recipients
Authors: STUBER THOMAS , EIGENMANN CHRISTA , DELACRÉTAZ ETIENNE
Published: July 2005

Introduction: Studies of recurrent ventricular tachycardia and ventricular fibrillation (VT/VF) have been limited to “electrical storms,” where recurrent arrhythmias necessitate repeated external cardioversions or defibrillations. Patients with an implantable cardioverter‐defibrillator (ICD) may also suffer frequently recurrent arrhythmias. The aim of this study was to analyze the temporal pattern and the clinical relevance of clustering ventricular arrhythmias in ICD recipients.

Methods: The incidence and the type of arrhythmias were determined by reviewing stored electrograms. VT/VF clusters were defined as the occurrence of three or more adequate and successful ICD interventions within 2 weeks. Two hundred and fourteen consecutive ICD recipients were followed during an average of 3.3 ± 2.2 years (698 patient‐years).

Results: Fifty‐one patients (24%) suffered 98 VT/VF clusters 21 ± 22 months after ICD implantation, 93% of these clusters consisting of recurrent regular VT. Monomorphic VT as index event leading to ICD implantation was the only factor predicting VT/VF clusters. Kaplan‐Meier estimates of the combined end‐point of death or heart transplantation showed a 5‐year event‐free survival of 67% versus 87% in patients with and without clusters, respectively (P = 0.026). Adjusted hazard ratios for death or heart transplantation in the group with arrhythmia clusters was 3.5 (95% confidence interval 1.5–7.9 P = 0.003).

Conclusions: VT/VF clusters are frequent late after ICD implantation particularly in patients who had VT as index‐event. As arrhythmias and recurrent ICD interventions are responsible for an important morbidity, there is a possible role for a prophylactic intervention. Furthermore, VT/VF clusters are an independent marker of increased risk of death or need for heart transplantation.
Validation of Dual‐Chamber Pacemaker Diagnostic Data Using Dual‐Channel Stored Electrograms
Authors: NOWAK BERND , McMEEKIN JAMES , KNOPS MARIE , WILLE BERND , SCHRÖDER EBERHARD , MORO CONCEPCION , OELHER MATTHIAS , CASTELLANOS EDUARDO , COUTU BENOIT , PETERSEN BEN , PFEIL WOLFGANG , KREUZER JOACHIM ,   on behalf of the Stored EGM in PulsarMax II and Discovery II Study Group
Published: July 2005

Background: Pacemaker diagnostic counters are used to guide device programming and patient management. However, these data are susceptible to inappropriate classification of events. The aim of this multicenter study was to evaluate pacemaker diagnostic data using stored intracardiac electrograms (EGMs).

Methods: The study included 351 patients (191 males, aged 71 ± 10 years) with standard indications for dual‐chamber pacemaker implantation. EGM triggers were atrial tachycardia (AT), ventricular tachycardia (VT), sudden bradycardia response (SBR), and pacemaker‐mediated tachycardia (PMT). For this study, the devices could store up to 5 EGMs of 8s each (with marker annotation and onset recording). After 3 months, the EGMs were analyzed and classified as “confirmed” if the EGM validated the trigger and as “false positive” if the EGM showed an event different from the trigger.

Results: Of the 1,003 EGMs available, the triggers were AT in 640 EGMs, VT in 76, SBR in 105, and PMT in 178 EGMs. Four EGMs were triggered by magnet application. The trigger was confirmed in 614 EGMs (62%): 62% of AT episodes, 18% of VT episodes, 100% of SBR episodes, and 54% of PMT episodes. In 385 cases (45%), the EGMs revealed false‐positive events due to far‐field sensing (39%), noise and myopotential sensing (26%), sinus tachycardias (21%), double counting (9%), exit block (4%), and undersensing (1%).

Conclusion: This large‐scale study of stored EGMs revealed their value in validating diagnostic counter data. Therapeutic decisions should not be based on diagnostic counters alone; they should be validated by sophisticated tools like stored EGMs.
Central Venous Occlusion Is Not an Obstacle to Device Upgrade with the Assistance of Laser Extraction
Authors: GULA LORNE J. , AMES ALYSON , WOODBURN ASHLEY , MATKINS JOHN , McCORMICK MICHAEL , BELL JEFFREY , SINK DEBORAH , McCONVILLE JAMES , EPSTEIN LAURENCE M.
Published: July 2005

Objective: To assess the efficacy and safety of laser‐assisted lead extraction for upgrade of existing pacemakers and defibrillators in patients with central venous obstruction.

Background: Implantable cardiac defibrillators and biventricular pacing have become the accepted therapeutic measures for patients with congestive heart failure. Many patients who are candidates for device therapy, however, already have existing right ventricular leads and the presence of central venous obstruction. Upgrade of existing devices in these patients is a dilemma, which is increasingly encountered by device‐implanting physicians. Laser‐assisted extraction of existing leads can facilitate access for device upgrade and provide an alternative to lead abandonment and contralateral implant.

Methods: We review our experience with laser‐assisted lead extraction in patients, referred for upgrade of existing devices, who were found to have, or known to have, ipsilateral subclavian vein occlusion.

Results: Over the past 3 years, 18 patients (13 men, 5 women; mean age 63.9 ± 16 years) with subclavian vein occlusion underwent successful laser‐assisted lead extraction (total 29 leads) and upgrade of existing leads to defibrillators and/or biventricular systems. Mean implant duration prior to extraction was 70.8 ± 43.5 (11–192) months. Cannulation of the coronary sinus and placement of a transvenous left ventricular lead were achieved in all 13 patients in whom it was attempted. No complications occurred.

Conclusions: Laser‐assisted lead extraction is a safe and effective approach, allowing for ipsilateral device upgrade in patients with existing devices and central venous obstruction.
Effect of Concomitant Antiarrhythmic Therapy on Survival in Patients with Implantable Cardioverter Defibrillators
Authors: HO ANDREW T. , PAI SUDHA M. , TIMOTHY PAM , PAI RAMDAS G.
Published: July 2005

Background: Application of implantable cardioverter defibrillator (ICD) therapy is expanding to include both primary and secondary prevention of sudden cardiac death and has been proven to be superior to conventional antiarrhythmic therapies. Concomitant antiarrhythmic drug therapy in patients with ICD is common. These drugs are potentially proarrhythmic, alter defibrillation thresholds, and may affect response to device therapy. However, the impact of concomitant antiarrhythmic drug therapy on survival in patients with ICD devices is unknown.

Methods: We investigated the effect of different antiarrhythmic drugs on survival when given concomitantly in 360 consecutive ICD patients from our university medical center. Mortality data were obtained from the national death index. Survival analysis was performed using the Kaplan‐Meier method. Corrections for significant covariates and group differences were made using the Cox regression model.

Results: Patients were followed up for 4.4 ± 3.7 years. There were 68 deaths over this period with a 5‐year survival of 80%. Patient characteristics were: age 62 ± 13 years, left ventricular (LV) ejection fraction (EF) 33 ± 17%, ischemic etiology of LV dysfunction 68%, diabetes mellitus 19%, hypertension 49%, atrial fibrillation 23%, digoxin 43%, β‐blocker 46%, amiodarone 28%, and sotalol 9%. The use of β‐blockers was associated with a better survival (P = 0.0005). This effect persisted after correcting for age, heart rate, EF, and ischemic etiology. The beneficial effect of β‐blocker was unrelated to its effect on heart rate. Digoxin use was associated with a lower survival only on univariate analysis (P = 0.006), but not after adjusting for other variables on a Cox regression model (P = 0.093). Amiodarone and sotalol were found to have a neutral effect on survival.

Conclusion: In patients with ICDs, β‐blockers had a favorable effect on survival. Sotalol and amiodarone had a neutral effect on survival. There was a trend toward a deleterious effect with digoxin use. These findings suggest a need for further investigation addressing survival effects of antiarrhythmic drugs when given concomitantly in patients with ICDs.
Clinical issues in perinatal mental health: new developments in the detection and treatment of perinatal mood and anxiety disorders
Authors: Austin M.‐P. , Priest S. R.
Published: July 2005

Objective:  This paper presents evidence of new developments in the detection and treatment of perinatal mood and anxiety disorders that have relevance for clinicians.

Method:  An electronic search was conducted in MEDLINE, CINAHL, PsychINFO and The Cochrane Library Database for the interval 1995–2005 for papers published in English.

Results:  New developments were identified as follows:  i) Broadening frames of reference within perinatal mental health.  ii) Impact of disorders upon offspring.  iii) Identifying women at risk of mental health problems.  iv) Prevention and early intervention strategies.  v) Treatments.

Conclusion:  Perinatal mental health is a rapidly expanding field that impacts upon the health and wellbeing of all members of families with infants and young children. An evidence base for best practice is slowly emerging but considerable work is still needed in relation to the identification of women at risk, standardisation of diagnostic procedures, reduction of adverse outcomes for women and infants, prevention, early intervention, and treatment of clinical disorders.
Adjunctive bright light in non‐seasonal major depression: results from clinician‐rated depression scales
Authors: Martiny K. , Lunde M. , Undén M. , Dam H. , Bech P.
Published: July 2005

Objective:  To investigate the use of bright light therapy as an adjunct treatment to sertraline in non‐seasonal major depression.

Method:  In a randomised double‐blind trial, 102 patients were treated for 5 weeks with either white bright light (10 000 lux, 1 h daily) or red dim light (50 lux, 30 min daily). All patients were treated with sertraline in a fixed dose of 50 mg daily. The clinician‐rated depression scales used were the Hamilton Depression Rating Scale (HAM‐D17), Hamilton six‐item subscale (HAM‐D6), Melancholia Scale (MES) and the seven ‘atypical’ items from the SIGH‐SAD.

Results:  One‐hundred and two patients were included in the study. Analyses showed that the reduction in depression scores in the bright light group was statistically significantly larger than in the dim light group on all scales. The scale most sensitive at endpoint was the HAM‐D6, which includes the core symptoms of depression.

Conclusion:  The study results support the use of bright light as an adjunct treatment to antidepressants in non‐seasonal depression.
One‐year outcome with antidepressant – treatment of bipolar depression
Authors: Joffe R. T. , MacQueen G. M. , Marriott M. , Young L. T.
Published: July 2005

Objective:  To examine the risk of relapse into mania or depression with varying duration of antidepressant treatment in a cohort of 59 patients with bipolar disorder.

Method:  An open naturalistic evaluation using life charting methods of patients with 1 year follow‐up, who responded to antidepressant treatment and who then less or more than 6 months of antidepressant treatment.

Results:  Patients who received more than 6 months of antidepressant treatment were less likely to relapse into depression at follow‐up of 1 year. There was no difference in relapse rates for mania in the different antidepressant treatment duration groups. Gender and bipolar subtype did not significantly affect relapse rates for depression or mania.

Conclusion:  Our data, taken with other studies, suggest that the duration of optimal antidepressant treatment in bipolar disorder must be further evaluated.
Palatine tonsils in smoker and non‐smoker patients: a pilot clinicopathological and ultrastructural study
Authors: Torre Valerio , Bucolo Sebastiano , Giordano Carlo , Cicciarello Rocco , Cavallari Vittorio , Garofalo Loredana , Beatrice Fabio
Published: July 2005

Background:  Tobacco smoke is a well‐known source of toxic, mutagenic and carcinogenic agents. The aim of the present preliminary study was to investigate the effects of cigarette smoking on lymphoid and non‐lymphoid tonsillar tissue.

Methods:  The study group consisted of 12 smoker and 10 non‐smoker patients complaining recurrent tonsillitis. Clinical data, histological findings and scanning electron microscopic analyses were considered. To the best of our knowledge, such an approach has not been previously adopted in a similar experimental model.

Results:  Smoker patients showed a longer history of recurrent tonsillitis, difficulties in clinical management and evident morphostructural changes than non‐smokers.

Conclusions:  These preliminary results suggest a possible interference of cigarette smoking with the therapy response as well as a possible role of tobacco smoke in impairment of inflammatory response. Results are critically analysed and discussed. Literature data on this subject are reviewed.
Recurrent herpes labialis: a pilot study of the efficacy of zinc therapy
Authors: Femiano F. , Gombos F. , Scully C.
Published: July 2005

Background:  The objective of this study was to investigate the effect of zinc on recurrent herpes labialis.

Materials/Methods:  Twenty patients (12 females; median age 26.6 years) with a history of recurrent herpes labialis >6 episodes each year were treated with systemic zinc sulphate 22.5 mg twice daily for the months of February, March, September and October. All patients were followed for 12 months.

Results:  Herpetic lesions reduced to <4 episodes (average 3) for the 12 months and the duration was <7 days for each episode (average 5.7).

Conclusions:  Systemic zinc sulphate appeared to reduce both the number of episodes and the time to recovery of herpes labialis.
Immunohistochemical detection of β‐catenin and adenomatous polyposis coli in ameloblastomas
Authors: Kumamoto H. , Ooya K.
Published: July 2005

Background:  To clarify the roles of the Wnt signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, expression of β‐catenin and adenomatous polyposis coli (APC) was analyzed in ameloblastomas as well as in tooth germs.

Methods:  Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined immunohistochemically with the use of antibodies against β‐catenin and APC.

Results:  Immunohistochemical reactivity for β‐catenin was detected in the cell membrane and cytoplasm of most odontogenic epithelial cells in tooth germs and ameloblastomas. Nuclear β‐catenin expression was recognized in nine of 40 ameloblastomas and two of five malignant ameloblastomas, but not in tooth germs. APC was evidently expressed in odontogenic epithelial cells neighboring the basement membrane in tooth germs and ameloblastomas, and the reactivity was significantly lower in benign and malignant ameloblastomas than in tooth germs. Follicular ameloblastomas and acanthomatous ameloblastomas tended to show high nuclear β‐catenin expression and low APC reactivity, as compared with other ameloblastoma variants.

Conclusion:  Expression of β‐catenin and APC in tooth germs and ameloblastomas suggests that aberration of the Wnt signaling pathway might play a role in oncogenesis and cytodifferentiation of odontogenic epithelium via deregulation of cell proliferation.
Parotid mycobacteriosis is frequently caused by Mycobacterium tuberculosis in advanced AIDS
Authors: Rangel A. L. C. A. , Coletta R. D. , Almeida O. P. , Graner E. , Lucena A. , Saldiva P. H. N. , Vargas P. A.
Published: July 2005

Background:  Tuberculosis is one of the leading infectious diseases in the world, with more than 2 million new cases annually. It is one of the main causes of death of human immunodeficiency virus (HIV)‐positive patients, involving multiple organs and particularly the lungs. Nevertheless there are few consistent studies about tuberculosis involving the parotid of HIV patients. The objective of this work was to describe the histological and immunohistochemical characteristics of 10 cases of mycobacteriosis involving the parotid of autopsied patients with advanced acquired immunodeficiency syndrome (AIDS), including identification of the Mycobacterium species.

Methods:  Detection of ‘M. tuberculosis complex’ was performed by polymerase chain reaction (PCR) and ligase chain reaction (LCR) and Mycobacterium avium by PCR.

Results:  All cases showed involvement of intraparotid lymph nodes, but the glandular parenchyma was affected in only three cases. Most of the cases (80%) presented a chronic non‐caseating granulomatous inflammation, and in two cases predominated foamy macrophages, full of bacteria, and no granuloma formation. In areas of mycobacteriosis, macrophages predominated followed by TCD8, B and TCD4 lymphocytes. All cases were infected by Mycobacterium genus and ‘M. tuberculosis complex’ was detected in five cases by LCR and in eight by PCR, while M. avium was positive in one case only, which was also positive for M. tuberculosis.

Conclusions:  Parotid mycobacteriosis in advanced AIDS is characterized by intraparotid lymph node non‐caseating inflammatory granulomatous lesion, caused mainly by M. tuberculosis.
Contact dermatitis to quinoline, corticosteroids and antibiotics after short time treatment of delayed wound healing following malignant melanoma excision in a young woman
Authors: Praessler Jana , Bauer Andrea , Elsner Peter , Kaatz Martin
Published: July 2005

Background: We describe a 20‐year old woman with retarded healing after a melanoma excision. After short time application of several creams containing antiseptic, antibiotic and anti‐inflammatory ingredients she developed a severe contact dermatitis. Patch testing revealed sensitizations against corticosteroids, an antibiotic and quinoline.

Conclusion: In our case multiple relevant contact sensitizations appeared within a short period of two months after excision of a malignant tumour.
Non‐invasive preoperative assessment of basal cell carcinoma of nodular and superficial types
Authors: Kuzmina Natalia , Talme Toomas , Lapins Jan , Emtestam Lennart
Published: July 2005

Background/aims: Although various biophysical properties can be used to distinguish basal cell carcinoma (BCC) tissue from normal skin, none permits typing of the tumour. In this study, we assessed nodular (NBCC) and superficial (SBCC) types of BCC using three different non‐invasive instruments and placed special emphasis on their clinical value as diagnostic tools.

Methods: We included 35 patients with 35 tumours (15 NBCC and 20 SBCC), which had been diagnosed clinically. All lesions were evaluated preoperatively with an instrument measuring electrical impedance (IMP). Methods for determining transepidermal water loss (TEWL) and laser Doppler (LD) were also used. Measurements were also made in healthy skin on the contralateral side as reference. The diagnosis was confirmed by histological examination.

Results: We found clear differences between the lesions and their reference values, using all three bioengineering techniques for NBCC and SBCC. The biophysical parameters of all types vary with anatomical location. Since most of the NBCC were located on the face and most SBCC on the trunk, their baseline impedance characteristics (i.e., impedance indices magnitude index (MIX) and imaginary part index (IMIX)) differed significantly. We therefore compared delta (a difference between the reference and tumour) MIX and IMIX of NBCC and SBCC instead of the absolute figures. We found no significant differences in TEWL, blood flow and IMP between the two types of BCC and attribute this to biological variation and electromagnetic noise.

Conclusions: As with LD and TEWL, definite differences in IMP were detected between healthy skin and BCC lesions. However, at this stage of development of the bioimpedance technique, we were unable to distinguish between the two types of BCC. An improved IMP device with semi‐ invasive probes or a more sophisticated type of data analysis may increase the diagnostic usefulness of the IMP method.
Effects of Different Doses of Adrenocorticotrophic Hormone on the Serum Lipoprotein Profile in Healthy Subjects
Authors: Rafnsson Arnar Thor , Johannsson Magnus , Olafsson Isleifur , Dallongeville Jean , Erfurth Eva‐Marie , Berg Anna‐Lena , Arnadottir Margret
Published: July 2005

Abstract: Adrenocorticotrophic hormone (ACTH) at pharmacological dosage has marked lipid‐lowering effects that may have therapeutic implications. The rationale behind the present investigation was the possible use of ACTH as a lipid‐lowering replacement for steroids. Thirty‐two healthy individuals were randomly divided into four groups of 8 each. Three ACTH groups received different doses of ACTH1–24 intramuscularly (0.1 mg, 0.5 mg and 1.0 mg daily for four days) and the control group received NaCl 0.9% 1 ml intramuscularly daily for four days. Moreover, 8 healthy subjects were given ACTH1–24 1.0 mg intramuscularly five times at an interval of four days. Blood and urine samples were collected at regular intervals. ACTH treatment at the dose of 1.0 mg daily lowered the serum concentrations of low density lipoprotein (LDL) cholesterol and apolipoprotein B by 28% and 22%, respectively, which is similar to previous observations. ACTH treatment at the doses of 0.5 mg and 0.1 mg gave smaller reductions (17% and 12%, and 9% and 8%, respectively) resulting in near linear dose‐response relationships. There were no changes in the control group. Only the ACTH dose of 1.0 mg resulted in significant changes when compared with the control group. During the ACTH administration at four‐days intervals, the serum concentrations of LDL cholesterol and apolipoprotein B reached the lowest values at 48 hr after an injection, remained there at 72 hr but were rising again at 96 hr. For effective lipid reduction, an ACTH dose of about 1 mg is needed and it should be given more often than every fourth day, probably every second or third day. With regard to the cortisol exposure, the results should be viewed in the light of calculations, presented in the paper, that 1 mg of ACTH is equivalent to 90 mg of cortisol administered parenterally.
Comparison of 3‐Hydroxy‐3‐methylglutaryl Coenzyme A (HMG‐CoA) Reductase Inhibitors (Statins) as Inhibitors of Cytochrome P450 2C8
Authors: Tornio Aleksi , Pasanen Marja K. , Laitila Jouko , Neuvonen Pertti J. , Backman Janne T.
Published: July 2005

Abstract: Statins are involved in different types of drug interactions. Our objective was to study the effect of statins on cytochrome P450 (CYP) 2C8‐mediated paclitaxel 6α‐hydroxylation by incubating paclitaxel and statins (0–100 μM) with pooled human liver microsomes. Simvastatin, lovastatin, atorvastatin and fluvastatin were the most potent inhibitors of CYP2C8 activity with Ki (IC50) values of 7.1 (9.6) μM, 8.4 (15) μM, 16 (38) μM and 19 (37) μM, respectively. Cerivastatin, simvastatin acid and lovastatin acid were less potent inhibitors with Ki (IC50) values ranging from 32 to 55 (30–67) μM. Rosuvastatin and pravastatin showed no appreciable effect on CYP2C8 activity even at 100 μM. In conclusion, all the statins tested, except rosuvastatin and pravastatin, had a significant inhibitory effect on the activity of CYP2C8 in vitro. Because many of the statins accumulate in the liver and because also their metabolites may inhibit CYP2C8 activity, in vivo studies are needed to investigate a possible interaction of simvastatin, lovastatin, atorvastatin and fluvastatin with CYP2C8 substrate drugs.
Porcine CYP2A Polymorphisms and Activity
Authors: Skaanild Mette T. , Friis Christian
Published: July 2005

Abstract: CYP2A6 in man catalyzes the oxidation of nicotine‐forming cotinine and 7‐hydroxylation of coumarin, which is used as test substrate for CYP2A6 in man. Large interindividual differences are found in man and some are due to genetic polymorphism. The 7‐hydroxylation of coumarin is present in pigs, and an inter‐individual variation has been found that might be due to polymorphisms. To enable the finding of polymorphism in pigs, the minipig cDNA was sequenced. Two cDNAs were found and translated to a 494 and a 487 amino acid long protein, both cDNAs were found in all but one pig. The 494 a.a. protein showed high homology to the human and 100% homology to the conventional pig CYP2A19 protein. In the wild type protein, all 6 substrate recognition sites were found, whereas the short protein only contained the first 5 substrate recognition sites. SSCP analysis revealed 3 polymorphisms. In order to study the effect of these polymorphisms on enzyme activity, microsomes were incubated with nicotine and coumarin. The polymorphisms appeared to have no effect on either enzyme activity as the specific enzyme activity towards nicotine and coumarin were approximately the same for all pigs. The specificity of pig CYP2A was investigated and it was found that the formation of cotinine correlated with the immunochemical level of CYP2A as did the coumarin hydroxylation. Anti‐human CYP2A inhibitory antibody inhibited coumarin 7‐hydroxylation by about 90% and formation of cotinine by 44–60% and 85–100% at substrate concentrations of 500 μM and 50 μM respectively, showing that coumarin and nicotine (50 μM) are very specific substrates for CYP2A in pigs, whereas the CYP2A only is responsible for about 50% of the cotinine formation at a 500 μM nicotine incubation concentration. These results show that the large interindividual differences in porcine CYP2A activity are not caused by polymorphisms but transcriptional regulation and the coumarin 7‐hydroxylation is as specific a reaction for porcine CYP2A as for human CYP2A6.
How Palatable Food Disrupts Appetite Regulation
Authors: Erlanson‐Albertsson Charlotte
Published: July 2005

Abstract: Appetite regulation is part of a feedback system that controls the energy balance, involving a complex interplay of hunger and satiety signals, produced in the hypothalamus as well as in peripheral organs. Hunger signals may be generated in peripheral organs (e.g. ghrelin) but most of them are expressed in the hypothalamus (neuropeptide Y, orexins, agouti‐related peptide, melanin concentrating hormone, endogenous opiates and dopamine) and are expressed during situations of energy deficiency. Some satiety signals, such as cholecystokinin, glucagon‐like peptide 1, peptide YY and enterostatin are released from the digestive tract in response to food intake. Others, such as leptin and insulin, are mobilized in response to perturbations in the nutritional state. Still others are generated in neurones of the hypothalamus (α‐melanocyte‐stimulating hormone and serotonin). Satiety signals act by inhibiting the expression of hunger signals and/or by blunting their effect. Palatable food, i.e. food rich in fat and sugar, up‐regulates the expression of hunger signals and satiety signals, at the same time blunting the response to satiety signals and activating the reward system. Hence, palatable food offsets normal appetite regulation, which may explain the increasing problem of obesity worldwide.
Activity of NADPH‐Cytochrome P‐450 Reductase of the Human Heart, Liver and Lungs in the Presence of (‐)‐Epigallocatechin Gallate, Quercetin and Resveratrol: An in vitro Study
Authors: Dudka Jaroslaw , Jodynis‐Liebert Jadwiga , Korobowicz Elzbieta , Burdan Franciszek , Korobowicz Agnieszka , Szumilo Justyna , Tokarska Edyta , Klepacz Robert , Murias Marek
Published: July 2005

Abstract: NADPH‐cytochrome P‐450 reductase (P‐450 reductase) plays a crucial role in the metabolism of many endogenic compounds and xenobiotics detoxication. The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P‐450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (‐)‐epigallocatechin gallate (EGCG), quercetin and resveratrol on P‐450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P‐450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P‐450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P‐450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P‐450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine.
Arachidonate‐regulated Ca2+‐selective (ARC) channel activity is modulated by phosphorylation and involves an A‐kinase anchoring protein
Authors: Mignen Olivier , Thompson Jill L. , Shuttleworth Trevor J.
Published: July 2005

In many non‐excitable cells, the predominant mode of agonist‐activated Ca2+ entry switches from the arachidonic acid‐regulated Ca2+ (ARC) channels at low agonist concentrations, to store‐operated channels at high concentrations. Underlying this process is the inhibition of the ARC channels by a calcineurin‐mediated dephosphorylation, which inhibits the ability of arachidonic acid to activate the channels. Following such a dephosphorylation, we found that restoration of the sensitivity of the ARC channels to arachidonic acid, as well as to low concentrations of carbachol, was specifically dependent on protein kinase A (PKA) activity. Inhibition of protein kinase C, protein kinase G or calmodulin‐activated kinase had no effect. This action of PKA was unaffected by prolonged intracellular dialysis, whilst disruption of the binding of PKA to A‐kinase anchoring proteins (AKAPs) inhibited currents through ARC channels, and blocked the PKA‐dependent effects. AKAP79, a protein which scaffolds both PKA and calcineurin, was shown to be present in the cells. These data illustrate the significance of PKA‐dependent phosphorylation and calcineurin‐dependent dephosphorylation in the overall regulation of ARC channel activity, and indicate the key role of an AKAP, possibly AKAP79, in the spatial organization these processes.
cAMP increases Ca2+‐dependent exocytosis through both PKA and Epac2 in mouse melanotrophs from pituitary tissue slices
Authors: Sedej Simon , Rose Tobias , Rupnik Marjan
Published: July 2005

Cyclic AMP regulates Ca2+‐dependent exocytosis through a classical protein kinase A (PKA)‐dependent and an alternative cAMP–guanine nucleotide exchange factor (GEF)/Epac‐dependent pathway in many secretory cells. Although increased cAMP is believed to double secretory output in isolated pituitary cells, the direct target(s) for cAMP action and a detailed and high‐time resolved analysis of the effect of intracellular cAMP levels on the secretory activity in melanotrophs are still lacking. We investigated the effect of 200 μm cAMP on the kinetics of secretory vesicle depletion in mouse melanotrophs from fresh pituitary tissue slices. The whole‐cell patch‐clamp technique was used to depolarize melanotrophs and increase the cytosolic Ca2+ concentration ([Ca2+]i). Exogenous cAMP elicited an about twofold increase in cumulative membrane capacitance change and ∼34% increase of high‐voltage activated Ca2+ channel amplitude. cAMP‐dependent mechanisms did not affect [Ca2+]i, since the application of forskolin failed to change [Ca2+]i in melanotrophs, a phenomenon readily observed in anterior lobe. Depolarization‐induced secretion resulted in two distinct kinetic components: a linear and a threshold component, both stimulated by cAMP. The linear component (ATP‐independent) probably represented the exocytosis of the release‐ready vesicles, whereas the threshold component was assigned to the exocytosis of secretory vesicles that required ATP‐dependent reaction(s) and > 800 nm[Ca2+]i. The linear component was modulated by 8‐pCPT‐2Me‐cAMP (Epac agonist), while either H‐89 (PKA inhibitor) or Rp‐cAMPS (the competitive antagonist of cAMP binding to PKA) completely prevented the action of cAMP on the threshold component. In line with this, 6‐Phe‐cAMP, (PKA agonist), increased the threshold component. From our study, we suggest that the stimulation of cAMP production by application of oestrogen, as found in pregnant mice, increases the efficacy of the hormonal output through both PKA and cAMP–GEFII/Epac2‐dependent mechanisms.
GRIP Deuterium Excess Reveals Rapid and Orbital-Scale Changes in Greenland Moisture Origin
Authors: Masson-Delmotte V. , Jouzel J. , Landais A. , Stievenard M. , Johnsen S. J. , White J. W. C. , Werner M. , Sveinbjornsdottir A. , Fuhrer K.
Published: July 2005

The Northern Hemisphere hydrological cycle is a key factor coupling ice sheets, ocean circulation, and polar amplification of climate change. Here we present a Northern Hemisphere deuterium excess profile covering one climatic cycle, constructed with the use of δ
18
O and δD Greenland Ice Core Project (GRIP) records. Past changes in Greenland source and site temperatures are quantified with precipitation seasonality taken into account. The imprint of obliquity is evidenced in the site-to-source temperature gradient at orbital scale. At the millennial time scale, GRIP source temperature changes reflect southward shifts of the geographical locations of moisture sources during cold events, and these rapid shifts are associated with large-scale changes in atmospheric circulation.
Cell-to-Cell Transfer of Bacterial Outer Membrane Lipoproteins
Authors: Nudleman Eric , Wall Daniel , Kaiser Dale
Published: July 2005

Myxococcus xanthus
cells can glide forward by retracting type IV pili. Tgl, an outer membrane lipoprotein, is necessary to assemble pili. Tgl mutants can be transiently “stimulated” if brought into end-to-end contact with
tgl
+
donor cells. By separating the stimulated recipient cells from donor cells, we found that Tgl protein was transferred from the donors to the rescued recipient cells. Mutants lacking CglB lipoprotein, which is part of a second gliding engine, could also be stimulated, and CglB protein was transferred from donor to recipient cells. The high transfer efficiency of Tgl and CglB proteins suggests that donor and recipient cells briefly fuse their outer membranes.
On-Wire Lithography
Authors: Qin Lidong , Park Sungho , Huang Ling , Mirkin Chad A.
Published: July 2005

We report a high-throughput procedure for lithographically processing one-dimensional nanowires. This procedure, termed on-wire lithography, combines advances in template-directed synthesis of nanowires with electrochemical deposition and wet-chemical etching and allows routine fabrication of face-to-face disk arrays and gap structures in the range of five to several hundred nanometers. We studied the transport properties of 13-nanometer gaps with and without nanoscopic amounts of conducting polymers deposited within by dip-pen nanolithography.
A Magnetic Nanoprobe Technology for Detecting Molecular Interactions in Live Cells
Authors: Won Jaejoon , Kim Mina , Yi Yong-Weon , Kim Young Ho , Jung Neoncheol , Kim Tae Kook
Published: July 2005

Technologies to assess the molecular targets of biomolecules in living cells are lacking. We have developed a technology called magnetism-based interaction capture (MAGIC) that identifies molecular targets on the basis of induced movement of superparamagnetic nanoparticles inside living cells. Efficient intracellular uptake of superparamagnetic nanoparticles (coated with a small molecule of interest) was mediated by a transducible fusogenic peptide. These nanoprobes captured the small molecule's labeled target protein and were translocated in a direction specified by the magnetic field. Use of MAGIC in genome-wide expression screening identified multiple protein targets of a drug. MAGIC was also used to monitor signal-dependent modification and multiple interactions of proteins.
The Many Trials of Galileo Galilei
Authors: Machamer Peter
Published: July 2005

Retrying Galileo 1633-1992
.
By Maurice Finocchiaro
. University of California Press, Berkeley, CA, 2005. 497 pp. $50, £32.50. ISBN 0-520-24261-0.

The author offers a finely documented account of the aftermath, repercussions, and reinterpretations of Galileo's trial from the 17th century into the 1990s.
Human Cytomegalovirus TRS1 and IRS1 Gene Products Block the Double-Stranded-RNA-Activated Host Protein Shutoff Response Induced by Herpes Simplex Virus Type 1 Infection
Authors: Cassady Kevin A.
Published: July 2005

Human cytomegalovirus (HCMV) attachment and entry stimulates the expression of cellular interferon-inducible genes, many of which target important cellular functions necessary for viral replication. Double-stranded RNA-dependent host protein kinase (PKR) is an interferon-inducible gene product that limits viral replication by inhibiting protein translation in the infected cell. It was anticipated that HCMV encodes gene products that facilitate the evasion of this PKR-mediated antiviral response. Using a Δγ
1
34.5 herpes simplex virus type 1 (HSV-1) recombinant that triggers PKR-mediated protein synthesis shutoff, experiments identified an HCMV gene product expressed in the initial hours of infection that allows continued protein synthesis in the infected cell. Recombinant HSV-1 viruses expressing either the HCMV TRS1 or IRS1 protein demonstrate that either of these HCMV gene products allows the Δγ
1
34.5 recombinant viruses to evade PKR-mediated protein shutoff and maintain late viral protein synthesis.