bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcoronary Ablation of Septal Hypertrophy Does Not Alter ICD Intervention Rates in High Risk Patients with Hypertrophic Obstructive Cardiomyopathy
Authors: LAWRENZ THORSTEN , OBERGASSEL LUDGER , LIEDER FRANK , LEUNER CHRISTIAN , STRUNK‐MUELLER CLAUDIA , MEYER DOROTHEE , VILSENDORF ZU , BEER GERALD , KUHN HORST
Published: April 2005

Introduction: Transcoronary ablation of septal hypertrophy (TASH) is safe and effectively reduces the intraventricular gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM). To analyze the potential of anti‐ and proarrhythmic effects of TASH, we studied the discharge rates of implanted cardioverter defibrillators (ICD) in patients with HOCM who are at a high risk for sudden cardiac death.

Methods: ICD and TASH were performed in 15 patients. Indications for ICD‐implantation were secondary prevention in nine patients after resuscitation from cardiac arrest with documented ventricular fibrillation (n = 7) or sustained ventricular tachycardia (n = 2) and primary prevention in 6 patients with a family history of sudden deaths, nonsustained ventricular tachycardia, and/or syncope. All the patients had severe symptoms due to HOCM (NYHA functional class = 2.9).

Results: During a mean follow‐up time of 41 ± 22.7 months following the TASH procedure, 4 patients had episodes of appropriate discharges (8% per year). The discharge rate in the secondary prevention group was 10% per year and 5% in the group with primary prophylactic implants. Three patients died during follow‐up (one each of pulmonary embolism, stroke, and sudden death).

Conclusion: In conclusion, on the basis of ICD‐discharge rates in HOCM‐patients at high risk for sudden death, there is no evidence for an unfavorable arrhythmogenic effect of TASH. The efficacy of ICD treatment for the prevention of sudden cardiac death in HOCM could be confirmed, however, mortality is high in this cohort of hypertrophic cardiomyopathy patients.
Isotretinoin (13‐Cis‐Retinoic Acid) Associated Atrial Tachycardia
Authors: HASDEMIR CAN , SAGCAN ABDI , SEKURI CEVAT , ILDIZLI MUGE , ULUCAN CEM , CEYLAN CAN
Published: April 2005

We describe a 16‐year‐old boy who presented with palpitations for 1 week while being on isotretinoin treatment for nodulocystic facial acne for 3 months. Twenty four‐hour Holter monitoring showed frequent premature atrial beats and episodes of nonsustained atrial tachycardia. He never had any episodes of palpitations previously. His complaints almost disappeared within a week after stopping the treatment. He remained asymptomatic since the discontinuation of the drug. The temporal relationship between isotretinoin treatment and patient's symptoms in the presence of documented arrhythmia suggests a drug‐related cause. As a result, clinicians should be aware of the possible arrhythmogenic effect of isotretinoin.
Late Perforation of the Heart, Pericardium, and Diaphragm by an Active‐Fixation Ventricular Lead
Authors: AKYOL AHMET , AYDIN ALPER , ERDINLER IZZET , OGUZ ENIS
Published: April 2005

This case report describes a late perforation of right heart wall, pericardium, and diaphragm by an active‐fixation ventricular lead without development of pericardial effusion and cardiac tamponade even under oral warfarin treatment.
Introduction of Permanent Cardiac Stimulation/Defibrillation Leads Via the Retro‐Pectoral Veins
Authors: CAMOUS J.P. , RAYBAUD F. , LESTO I. , BENOIT P.H.
Published: April 2005

When the cephalic vein route is not easily accessible for the introduction of permanent stimulation/defibrillation leads, retro‐pectoral veins can be looked for, which are usually present and suitable in most patients. As with the cephalic vein route, it is a safer approach than direct subclavian vein puncture. Moreover, using a guidewire and a split introducer increases the rate of successful cannulation.
Electrophysiologic Study‐Guided Therapy with Sotalol for Life‐Threatening Ventricular Tachyarrhythmias
Authors: WATANABE HIROSHI , CHINUSHI MASAOMI , WASHIZUKA TAKASHI , SUGIURA HIROTAKA , HIRONO TAKASHI , KOMURA SATORU , HOSAKA YUKIO , TANABE YASUTAKA , FURUSHIMA HIROSHI , FUJITA SATOSHI , KATO KIMINORI , AIZAWA YOSHIFUSA
Published: April 2005

The aim of this study was to investigate the long‐term efficacy and safety of electrophysiologic study (EPS)‐guided sotalol administration combined with implantable cardioverter defibrillators (ICD) for ventricular tachyarrhythmias (VTA). This study enrolled 92 patients with both structural heart disease and sustained VTA. Sotalol was administered to 57 patients, and its efficacy was assessed by EPS. Long‐term treatment was continued in combination with ICD in 31 patients (57%) whose VTA was no longer inducible (responder group) and in 16 patients whose VTA remained inducible (nonresponder group). The long‐term outcomes were compared among the responder group, the nonresponder group, and 35 ICD recipients untreated with antiarrhythmic drugs (ICD‐only group). During a mean follow‐up of 44 ± 33 months, the recurrence of VTA was not significantly different between all patients treated with sotalol (30%) and patients in the ICD‐only group (46%). However, the recurrence of VTA was significantly lower in the responder (13%) than in the nonresponder (63%) or the ICD‐only groups (46%). There was no significant difference in VTA recurrence between the nonresponder and the ICD‐only groups. One patient each in the responder and the ICD‐only groups died suddenly, and all‐cause mortality was similar in the three groups. The incidence of inappropriate ICD discharges was less in the sotalol than in the ICD‐only groups. No patient had to discontinue long‐term sotalol treatment because of the adverse effects. In conclusion, sotalol reduced VTA recurrence in the responding patients and inappropriate ICD discharge. EPS may predict the efficacy of sotalol for VTA recurrence.
Cardiac Resynchronization Induces Favorable Neurohumoral Changes
Authors: EROL‐YILMAZ AYTEN , VERBERNE HEIN J. , SCHRAMA TIM A. , HRUDOVA JANA , DE WINTER ROBBERT J. , VAN ECK‐SMIT BERTHE L.F. , DE BRUIN RIANNE , BAX JEROEN J. , SCHALIJ MARTIN J. , WILDE ARTHUR A. , TUKKIE RAYMOND
Published: April 2005

Aim: The aim of this article is to examine whether cardiac resynchronization therapy (CRT) induces improvements in the neurohumoral system.

Methods and Results: Thirteen patients with HF (left ventricular (LV) ejection fraction <35%) were included. Before and after 6 months of CRT, myocardial 123I‐metaiodobenzylguanidine (123I‐MIBG) uptake indices, used as an index of neural norepinephrine reuptake and retention, and brain natriuretic peptide (BNP) levels, used as an index of LV end‐diastolic pressure, NYHA classification and echocardiographic indices were assessed. Six months of CRT resulted in significant improvement in (1) NYHA classification and reduction in QRS width (P < 0.001), (2) decrease of LV end‐diastolic diameter (P = 0.005), LV end‐systolic diameter (P = 0.005), septal to lateral delay (P = 0.01) and mitral regurgitation (MR, P = 0.04), (3) delayed 123I‐MIBG heart/mediastinum ratios improved (P = 0.03) and 123I‐MIBG washout decreased (P = 0.001), and (4) BNP levels decreased (P = 0.001).

Conclusions: Parallel to significant functional improvement and echocardiographic reverse remodeling and resynchronization, our data indicate that CRT induces favorable changes in the neurohumoral system.
Safe Performance of Magnetic Resonance Imaging on a Patient with an ICD
Authors: WOLLMANN CHRISTIAN , GRUDE MATTHIAS , TOMBACH BERND , KUGEL HARALD , HEINDEL WALTER , BREITHARDT GÜNTER , BÖCKER DIRK , VAHLHAUS CHRISTIAN
Published: April 2005

This is a report on a patient with an implanted cardioverter defibrillator (ICD) who intentionally underwent magnetic resonance imaging (MRI) of a malignant brain tumor. To avoid inadequate detection of ventricular tachycardia (VT) or ventricular fibrillation (VF), the ICD was inactivated by programming the VT‐detection and VT/VF‐therapy status off. The patient came through the protocol safely and without any difficulty or discomfort. There was no arrhythmic event. MRI affected neither programmed data nor the function of the ICD system.
Longitudinally Partitioned Coronary Sinus: An Unusual Anomaly of the Coronary Venous System
Authors: TADA HIROSHI , ITO SACHIKO , NAITO SHIGETO , OSHIMA SHIGERU , TANIGUCHI KOICHI
Published: April 2005

We report a case of a patient with advanced heart failure who had a longitudinally partitioned coronary sinus. With multidirectional fluoroscopic views and a careful approach to the target lumen, a left ventricular lead for biventricular pacing was placed successfully in the left marginal vein.
Infrequent Syncope in a Heavy Vehicle Driver
Authors: CHUA RODERICK , THOMAS STUART P.
Published: April 2005

We present a case study of a truck driver with sinus node dysfunction diagnosed with the help of an implantable loop recorder more than 18 months after implantation. This case emphasizes that cardiogenic syncope may be very infrequent and its diagnosis can be elusive despite extensive testing.
Rate‐Dependent AV Delay Optimization in Cardiac Resynchronization Therapy
Authors: SCHARF CHRISTOPH , LI PENG , MUNTWYLER JÖRG , CHUGH AMAN , ORAL HAKAN , PELOSI FRANK , MORADY FRED , ARMSTRONG WILLIAM F.
Published: April 2005

Background: During cardiac resynchronization therapy (CRT), cardiac performance is dependent on an optimized atrioventricular delay (AVD). However, the optimal AVD at different heart rates has not been defined yet during CRT.

Method: The effects of an increase in heart rate by pacing or physical exercise on optimal AVD were studied in 36 patients with biventricular pacemakers/defibrillators. The velocity time integral (VTI) in the left ventricular outflow tract (LVOT) was measured with pulsed Doppler either at three different paced heart rates in the supine position or in seated position before and after physical exercise.

Results: The baseline AVD was optimized to 99 ± 19 ms in the supine and 84 ± 22 ms in the seated position. When the heart rate was increased by DDD pacing, there was a positive linear relationship between an increase in heart rate, in AVD and in VTI (LVOT‐VTI + 0.047 cm/s per 10 beats per minute (bpm) heart rate increase per 20 ms increase in AVD, P = 0.007). A similar but more pronounced relationship was found after physical exercise in the seated position (LVOT‐VTI + 0.146 cm/s per 10 bpm heart rate increase per 20 ms increase of AVD, P = 0.013). This effect was observed in patients with and without AV block and mitral regurgitation.

Conclusions: In conclusion, the systolic performance of the dilated ventricle, which depends on an elevated preload, is critically affected by the appropriate timing of the AVD during exercise. In contrast to normal pacemaker patients, in CRT the relatively short baseline AVD should be prolonged at increased heart rates. Further studies with other means of measuring exercise cardiac performance are needed to confirm these unexpected findings.
A Comparative Study of the Action of Dexamethasone Sodium Phosphate and Dexamethasone Acetate in Steroid‐Eluting Pacemaker Leads
Authors: SINGARAYAR SURESH , KISTLER PETER M. , DE WINTER CHANTAL , MOND HARRY
Published: April 2005

Background: The aim of this study was to characterize acute and medium‐term pacemaker lead performance with the two most commonly used glucocorticosteroids: dexamethasone sodium phosphate and dexamethasone acetate.

Methods: Forty sets of atrial and ventricular passive‐fixation leads containing either dexamethasone sodium phosphate or dexamethasone acetate were implanted as dual chamber pacemakers. Randomization was equally distributed to both arms of the study. Stimulation thresholds, lead impedance, and sensing were measured on the day of implant, day 1, 1 month, 3 months, and 6 months following the implant.

Results: For the dexamethasone sodium phosphate arm, the atrial stimulation thresholds were 0.9 ± 0.1 V at implant and 0.8 ± 0.1 V at 6 months, and in the ventricle 0.5 ± 0.1 V at implant and 0.6 ± 0.1 V at 6 months. In the dexamethasone acetate arm, the atrial stimulation thresholds were 0.7 ± 0.1 V at implant and at 6 months, and in the ventricle 0.5 ± 0.1 V at implant and at 6 months. There were no significant differences between dexamethasone sodium phosphate or dexamethasone acetate leads for stimulation thresholds at any of the intervals of follow‐up. P‐ and R‐wave sensing were similarly maintained over the duration of follow‐up with no significant differences between groups at any of the intervals of follow‐up. Pacing lead impedance showed a trend towards lower values in the dexamethasone acetate arm, which only reached statistical significance at 3 months and beyond for ventricular leads.

Conclusions: Leads containing dexamethasone sodium phosphate and dexamethasone acetate demonstrate equivalent and excellent acute and medium‐term pacemaker lead performance characteristics.
Is Magnetic Resonance Imaging Safe in Cardiac Pacemaker Recipients?
Authors: DEL OJO J. LEAL , MOYA F. , VILLALBA J. , SANZ O. , PAVÓN R. , GARCIA D. , PASTOR L.
Published: April 2005

Magnetic resonance imaging (MRI) is currently contraindicated in cardiac pacemaker (PM) recipients. The objectives of this prospective study were to (1) reassess the risks of performing an MRI scan in patients with PM, (2) compared the pacing functions before and after the exposure to MRI, and (3) monitor the development of possible adverse effects. Thirteen patients implanted with an Affinity™ DR model 5330 PMs (St. Jude Medical) connected to a Tendril™ model 1388 leads (St. Jude Medical) underwent 2.0 T‐MRI for a variety of indications. All patients displayed a stable spontaneous rhythm at the time of the MRI scan and were not considered to be PM‐dependent. The sensing and pacing functions were analyzed and the impedance of both leads was measured before and after the scan. The MRI scan was performed with all PM programmed in DDD mode. The sensing configuration was bipolar. All patients were monitored utilizing a standard electrocardiographic monitor and direct verbal communication. PM Inhibition, asynchronous pacing, or inappropriately rapid pacing was not observed. No patient reported discomfort, heat, or motion sensation at the PM implant site. There were no significant differences in the sensing, stimulation, AutoCapture® threshold, and lead impedance measurements before and after MRI. The results of this study suggest that performing 2.0 T‐MRI scans in patients with Affinity™ DR model 5330 PM connected to a Tendril™ model 1388 lead is safe.
Is Lowest‐Low Fertility in Europe Explained by the Postponement of Childbearing?
Authors: Sobotka Tomáš
Published: April 2005

In 2001, more than half of Europe's population lived in countries with a total fertility rate (TFR) at or below 1.3. Use of the adjusted TFR proposed by Bongaarts and Feeney, which takes into account the effects of the ongoing fertility postponement, changes the European fertility map considerably. All 27 countries analyzed had adjusted TFRs in 1995–2000 above 1.4. Thus, the “lowest‐low” fertility in Europe may be interpreted as a temporary consequence of the increasing age at motherhood. However, substantial regional differences in fertility level across Europe persist even when the differential pace of fertility postponement is taken into account. The estimated adjusted TFRs in Europe (1.63) and in the 25‐member European Union (1.71) contrast with the TFR levels of 1.40 and 1.46, respectively. These seemingly small differences have vastly different implications in terms of the potential long‐term pace of population decline.
Contradictions in Nigeria's Fertility Transition: The Burdens and Benefits of Having People
Authors: Smith Daniel Jordan
Published: April 2005

Nigeria appears to be experiencing a transition to lower fertility. Based on ethnographic research, this article shows how Nigerians navigate a paradoxical political‐economic and cultural context, wherein they face powerful pressures both to limit their fertility and to have relatively large families. The main argument advanced here is that Nigerians' fertility behavior must be understood in the context of the ways that parenthood, children, family, and kinship are inextricably intertwined with how people survive in a political economy organized around patron‐clientism. Despite the fact that fertility transition is widely associated with broad processes of modernization and development, ordinary Nigerians experience the pressures to limit fertility in terms of a failed economy, development disappointments, and personal hardship–even while they see relatively smaller families as essential if they are to educate their children properly and adapt to a changing society.
Demographic Theory: A Long View
Authors: Caldwell John C.
Published: April 2005

This essay argues that demographic theory over the last half‐century has substituted short‐term explanations, often focusing on single demographic events, for long‐term theory. This means not only that the explanations cannot be employed to forecast the situation in the more distant future, but they are inadequate even for short‐term analysis. A basis for a longer‐term theory of fertility transition is proposed, employing the concept of social structure and demographic behavior adjusting, slowly and after a considerable lag, to each of three modes of production. The focus is on the transition from agricultural to industrial production, especially as this is occurring in the most advanced industrial societies. Three major conclusions are drawn. (1) Unanticipated fertility changes over the last 50 years can be incorporated within a single demographic transition theory. (2) Societal and demographic changes are still at an early stage of their transition to full adjustment to industrialization. (3) The trend, associated with women's participation in the work force, toward below‐replacement fertility will continue, but at some stage most governments will probably attempt to raise fertility to replacement level even if the effort is extremely expensive and slows economic growth.
Preventing Stroke in Atrial Fibrillation: The SPORTIF Programme
Authors: Lip Gregory Y.H.
Published: April 2005

Atrial fibrillation (AF) is the most common cardiac risk factor for stroke. Oral anticoagulants such as the vitamin K antagonist warfarin have been proven effective in reducing the risk of stroke in AF. Warfarin, however, has many disadvantages including the need for coagulation monitoring, a narrow therapeutic index, inter-/intra-patient variability and food–drug interactions. As a result, warfarin is underused in clinical practice and a viable alternative is needed. Ximelagatran, the first oral direct thrombin inhibitor, is given as a fixed dose, does not have a narrow therapeutic index, has low potential for drug interactions, has no significant food interactions and does not require coagulation monitoring. Ximelagatran has been evaluated in the Stroke Prevention using an ORal direct Thrombin Inhibitor in atrial Fibrillation (SPORTIF) trial programme, the largest clinical trials of antithrombotic therapy for stroke prevention in AF to date. The phase III trials, SPORTIF III and V, compared ximelagatran (36 mg twice daily) with well-controlled warfarin (international normalized ratio 2.0–3.0) in a combined population of more than 7,000 moderate- to high-risk AF patients. Data from SPORTIF III show an absolute reduction in stroke and systemic embolic events with ximelagatran compared with warfarin at 21 months (1.6 vs. 2.3% per year, respectively; p = 0.10). Preliminary data from SPORTIF V appear to further support non-inferiority between the two agents. On-treatment analysis of the rate of major bleeding events shows an absolute, nonsignificant reduction in the event rate per year with ximelagatran versus warfarin in both studies. The results of SPORTIF III and V demonstrate that a fixed oral dose of ximelagatran, without coagulation monitoring, is comparable to dose-adjusted warfarin in preventing stroke and other thromboembolic complications among moderate- to high-risk AF patients and has a lower rate of both major and minor bleeding. With its positive benefit-risk ratio, ximelagatran may increase the population of eligible patients for anticoagulation with AF and maximize the potential of anticoagulation in the prevention of stroke.
Case-Control Association Studies in Mixed Populations: Correcting Using Genomic Control
Authors: Shmulewitz Dvora , Zhang Junying , Greenberg David A.
Published: April 2005

Objective: Case-control association studies in mixed populations can result in spurious disease-marker associations if subpopulation disease prevalence and marker frequencies both differ. Genomic control (GC) uses neutral loci to correct for spurious association (due to population stratification), but how well this works remains undetermined. Methods: We simulated and mixed populations with different disease and marker frequencies but without marker-disease association. We generated case-control datasets, calculated the χ2 for disease association with each marker, and applied two GC procedures, dividing by the mean χ2 or median-χ2/0.456. Results: Corrections became conservative (false positive rate [FPR] <5%) with increasing subpopulation prevalence and marker differences. The mean correction resulted in FPRs close to 5% at average subpopulation allele frequency differences <0.26, but inclusion of just a few markers with large frequency differences resulted in conservative FPRs. FPRs from the median correction were mostly conservative but became anticonservative when a few markers with large frequency differences were included. Conclusion: GC can both lead to a notable loss of power to detect a true association (conservative) in many circumstances or may fail to eliminate the spurious associations (anticonservative). The mean correction factor is useful in certain situations to correct population stratification, but it is difficult to know when those situations exist.
Comparative Study of Multipoint Methods for Genotype Error Detection
Authors: Mukhopadhyay Nandita , Buxbaum Sarah G. , Weeks Daniel E.
Published: April 2005

Several programs are currently available for the detection of genotyping error that may or may not be Mendelianly inconsistent. However, no systematic study exists that evaluates their performance under varying pedigree structures and sizes, marker spacing, and allele frequencies. Our simulation study compares four multipoint methods: Merlin, Mendel4, SimWalk2, and Sibmed. We look at empirical thresholds, power, and false-positive rates on 7 small pedigree structures that included sibships with and without genotyped parents, and a three-generation pedigree, using 11 microsatellite markers with 3 different map spacings. Simulated data includes 5,000 replicates of each pedigree structure and marker map, with random genotyping errors in about 4% of the middle marker’s genotypes. We found that the default thresholds used by these programs provide low power (47–72%). Power is improved more by adding genotyped siblings than by using more closely spaced markers. Some mistyping methods are sensitive to the frequencies of the observed alleles. Siblings of mistyped individuals have elevated false-positive rates, as do markers close to the mistyped marker. We conclude that thresholds should be decided based on the pedigree and marker data and that greater focus should be placed on modeling genotyping error when computing likelihoods, rather than on detecting and eliminating genotyping errors.
Cellular and Molecular Gateways to Urolithiasis: A New Insight
Authors: Dal Moro Fabrizio , Mancini Mariangela , Tavolini Ivan Matteo , De Marco Vincenzo , Bassi Pierfrancesco
Published: April 2005

Urolithiasis is a relevant clinical problem in everyday practice with a subsequent burden for the health system. Urolithiasis is classically explained as the derangement in the process of biomineralization involving the equilibrium between promoters and inhibitors of crystallization: a deficit of one or several inhibitors or an excess of one or several promoters plays a pivotal role in the stone formation. The revolutionary introduction of the molecular biology in medicine has given a new insight in urolithiasis too. Genetic factors have also been postulated to play an important role. A review of the current knowledge on urolithiasis based upon a molecular and genetic approach is reported.
Micturition Syncope due to Paraprostatic Pheochromocytoma
Authors: Padevit Christian , John Hubert , Gunz Anja , Wiesli Peter , Hauri Dieter , Schmid Christoph
Published: April 2005

Paraprostatic pheochromocytoma is a very rare localization of extra-adrenal pheochromocytoma. The clinical and anatomical features of a 41-year-old man are described.
‘Successful’ Chemo- and Radiotherapy prior to Radical Cystectomy Does Not Necessarily Correlate with Clinical Course in Small Cell Carcinoma of the Bladder
Authors: Sejima Takehiro , Miyagawa Ikuo
Published: April 2005

We report 2 cases in which chemo- and radiotherapy induced pathological remission prior to radical cystectomy in small cell carcinoma of the bladder. However, one of these cases suffered a local recurrence 8 months after surgery.
Influence of Various Cytokines on Adhesion and Migration of the Colorectal Adenocarcinoma Cell Line HRT-18
Authors: Köbel Martin , Budianto Daniel , Schmitt Wolfgang D. , Borsi Laura , Siri Annalisa , Hauptmann Steffen
Published: April 2005

The stroma of colorectal adenocarcinoma contains both abundant extracellular matrix (ECM) and an inflammatory cell infiltrate. The latter is the source of various cytokines, present in different concentrations in the tumor cell microenvironment. The aim of the present study was to investigate whether cytokines act as motility factors for HRT-18 rectal carcinoma cells and if this effect depends on the ECM. The main result of our study is that cytokines affect tumor cell motility in a matrix-dependent manner, and that stimulatory and inhibitory effects may depend on the composition of the ECM. Hepatocyte growth factor/scatter factor was the strongest migration factor for HRT-18 cells independent of the ECM. On the other hand, IL-6 was a strong migration stimulator for cells on Tenascin-C but was inhibitory on collagen type V. Therefore, different degrees of invasiveness at the tumor-host interface are not necessarily related to specific genetic alterations but might be related to different environmental conditions as well.
Surgical Outcome in Superficially Spreading Early Gastric Cancer
Authors: Kunisaki Chikara , Akiyama Hirotoshi , Nomura Masato , Matsuda Goro , Otsuka Yuichi , Ono Hidetaka , Shimada Hiroshi
Published: April 2005

Objectives: Superficially spreading early gastric cancer is characterized by wide horizontal extension without deep vertical invasion. This study aimed to clarify the clinicopathological characteristics and prognosis of this rare disease. Methods: We defined superficially spreading early gastric cancer as any tumor invading the submucosal layer that measured ≧60 mm in diameter. The clinicopathological characteristics and results of surgery were compared between 60 patients with superficially spreading tumors and 621 patients with the common type (<60 mm in diameter). Results: Forsuperficially spreading cancers,significantly higher numbers of female patients, undifferentiated and scirrhous types, infiltrating growth and lymph node metastases were seen. The number of metastatic lymph nodes was greater than in the common type. There was no significant difference in the distribution of metastatic lymph nodes between the two groups. For superficially spreading tumors, wide gastrectomy with extended lymph node dissection was frequently employed. Lymph node metastasis, but not tumor diameter, was a prognostic factor in uni- and multivariate analyses. Conclusions:Although superficially spreading early gastric cancer has histologically distinct properties, gastrectomy with lymph node dissection with sufficient surgical margin could be a suitable treatment.
High Efficacy and Low Toxicity of Weekly Docetaxel Given as First-Line Treatment for Metastatic Breast Cancer
Authors: Stemmler J. , Mair W. , Stauch M. , Papke J. , Deutsch G. , Abenhardt W. , Dorn B. , Kentenich C. , Malekmohammadi M. , Jackisch C. , Leinung S. , Brudler O. , Vehling-Kaiser U. , Stamp J. , Heinemann V.
Published: April 2005

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m2 weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles (3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses (median cumulative dose 339 mg/m2) was administered (range: 2–18). The overall response rate was 48.1% (95% CI: 34–61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months (intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status.
Increased Level of Granulocyte Elastase in Cervical Secretion Is an Independent Predictive Factor for Preterm Delivery
Authors: Nakai Akihito , Taniuchi Yoshinari , Miyake Hidehiko , Nakai Masako , Yokota Akishige , Takeshita Toshiyuki
Published: April 2005

Objective: The objective of this study was to explore whether increased levels of granulocyte elastase in cervical secretion is an independent predictive factor for preterm delivery before 34 weeks of gestation in the patient with preterm labor. Methods: One hundred and sixty-one women with preterm labor at 22–28 weeks of gestation were enrolled prospectively. The level of granulocyte elastase in cervical secretions was measured by immunoassay, vaginal secretions were collected for the microscopic evaluation of Gram-stained smears, and the uterine cervix was assessed by transvaginal ultrasonography. Results: Nineteen of 161 patients (12%) delivered before 34 weeks of gestation. Granulocyte elastase assessment had a sensitivity, specificity, positive predictive value, and negative predictive value for preterm delivery of 53, 75, 22 and 92%, respectively. A positive elastase assessment was associated with a relative risk for preterm delivery of 2.9 (95% CI 1.3–6.6), whereas a positive bacterial vaginosis assessment and shorter cervical length less than 25 mm demonstrated a relative risk of 1.9 (95% CI 0.8–4.6) and 1.5 (95% CI 0.6–5.0), respectively. Conclusion: The present study demonstrates that the risk of spontaneous preterm delivery before 34 weeks of gestation is increased in the women with preterm labor who are found to have an increased level of granulocyte elastase in cervical secretions.
In vitro Isolation and Cell Culture of Vestibular Inner Ear Melanocytes
Authors: Sanchez Hanke Marcos , Kief Sabine , Leuwer Rudolf , Koch Ulrich , Moll Ingrid , Brandner Johanna M.
Published: April 2005

Introduction: Melanocytes of the membranous labyrinth of the inner ear have been described morphologically in various contexts. Nature and functions of these cells are as yet not completely clear, even though several hypotheses exist regarding the same. The limited knowledge is due in part to a lack of methods regarding in vitro cell culture. The aim of this study was to describe conditions for the successful cell culture of vestibular inner ear melanocytes (VIEM), to compare their growth properties with those of epidermal melanocytes, and to characterize them immunohistochemically. Materials and Methods: Membranous labyrinth cells from freshly slaughtered sheep were isolated, and melanocytes and fibroblasts subsequently cultured. In addition, melanocytes from the skin of the same sheep were cultured. Antibodies specific to tyrosinase, tyrosinase-related protein 1 (TRP-1/Mel-5), and melanoma-specific antigen A (Melan A) were used to analyze the cultured cells. Results: The proliferation of VIEM was retarded in comparison to epidermal melanocytes. After 14 days, VIEM began to proliferate for the first time, whereas epidermal melanocytes proliferated already after 7 days. In contrast to epidermal melanocytes, the culturing process of VIEM seemed to be dependent on the presence of fibroblasts, and VIEM often accumulated in the vicinity of fibroblasts forming three-dimensional clusters. Moreover, VIEM showed a higher ratio of highly pigmented cells with a round cell shape and small dendrites in comparison to epidermal melanocytes. Immunohistochemical techniques proved the VIEM to be positive for Melan A, TRP-1 and, in the majority of cases, also for tyrosinase. Conclusion: We successfully cultured melanocytes of the inner ear vestibular labyrinth for the first time and demonstrated melanocytic characteristics of these cells. This accomplishment will provide the opportunity to investigate VIEM in more detail in future experiments.
Permanent Threshold Shift Caused by Acute Cochlear Mitochondrial Dysfunction Is Primarily Mediated by Degeneration of the Lateral Wall of the Cochlea
Authors: Okamoto Yasuhide , Hoya Noriyuki , Kamiya Kazusaku , Fujii Masato , Ogawa Kaoru , Matsunaga Tatsuo
Published: April 2005

Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model. Marked degeneration was detected in type 2 fibrocytes in the spiral prominence, type 4 fibrocytes in the spiral ligament, marginal cells and intermediate cells in the stria vascularis 3 h after 3-NP administration; these changes were progressive for at least 14 days. Less prominent degeneration was detected in type 1 and type 3 fibrocytes in the spiral ligament. These results indicate that permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by cellular degeneration in the lateral wall of the cochlea, and suggest that therapy of cochlear hearing loss due to acute energy failure may be achieved through protection and regeneration of the cochlear lateral wall.
Hypothalamic Resistin Immunoreactivity Is Reduced b y Obesity in the Mouse: Co-Localization with α-Melanostimulating Hormone
Authors: Wilkinson Michael , Wilkinson Diane , Wiesner Glen , Morash Barbara , Ur Ehud
Published: April 2005

Resistin is a new adipokine expressed in mouse, rat and human adipose tissue. Resistin may be an important link between obesity and insulin resistance, though this controversial view is complicated by the discovery of multiple sites of resistin expression, including human macrophages, placenta and pancreas. In previous studies we demonstrated that the mouse hypothalamo-pituitary system was also a site of resistin production. Pituitary resistin is developmentally regulated, reduced in the ob/ob mouse and severely down-regulated by food deprivation (24 h). An unexpected finding was that hypothalamic resistin mRNA remained unaffected by fasting. The present experiments examined the localization and possible regulation of hypothalamic resistin protein. Using immunohistochemistry we observed a complex network of resistin+ fibres extending rostrally from the arcuate nucleus of the hypothalamus (ARC) to the preoptic area. Labelled cell bodies occurred only in the ARC and in a periventricular region of the dorsal hypothalamus. Hypothalamic resistin immunoreactivity (ir) was unaffected by fasting (48 h) or by a high fat diet, but the periventricular staining was greatly increased in the lactating mouse. Marked reductions in resistin+ fibres were seen in brain tissue from: (a) ob/ob mice, (b) young mice made underweight for their age by raising them in large litters (20 pups per litter) and (c) mice with hypothalamic lesions induced by monosodium glutamate (MSG) or gold thioglucose (GTG). We speculate that the resistin-ir deficit in genetically obese mice, and in severely underweight mice, could be due to low or absent leptin. In contrast, though MSG- and GTG-treated mice have high levels of circulating leptin, in the presence of excessive visceral fat deposits, we hypothesize that damage to the ARC destroys the resistin+ cell bodies. This latter supposition led us to an additional hypothesis, that resistin-ir would be contained in neurons expressing the proopiomelanocortin (POMC) gene. This proved to be correct. Double label immunofluorescence histochemistry revealed that α-MSH-ir, a marker for POMC neurons, was co-localized with resistin-ir. In conclusion, our data reveal a second example of an adipocytokine co-localized with a hypothalamic neuropeptide. We reported previously that leptin was co-localized with oxytocin and vasopressin. RT-PCR analysis confirmed that resistin mRNA is readily detectable in ARC, but further work is required to determine whether the resistin gene is expressed in POMC neurons or if resistin is specifically accumulated by these cells. Nonetheless, our data suggest that the hypothalamus is a target tissue for resistin.
Memory Performance and the Growth Hormone/Insulin-Like Growth Factor Axis in Elderly: A Positron Emission Tomography Study
Authors: Arwert Lucia I. , Veltman Dick J. , Deijen Jan Berend , Lammertsma Adriaan A. , Jonker Cees , Drent Madeleine L.
Published: April 2005

The relationship between the growth hormone/insulin-like growth factor (GH-IGF)-I status and memory performance is studied in 24 elderly males and females, aged 75–85 years. Positron emission tomography (PET) was used to measure differences in regional cerebral blood flow during the performance of a delayed-non-match-to-sample (DNMTS) working memory task. Quality and speed of performance on the DNMTS task were measured separately for the easy items (3, 4 and 5 letters) and difficult items (6, 7 and 8 letters). Results were analyzed in two different groups based on the IGF-I level of the subjects (low or high IGF-I). Error rates on the working memory task were not different, but the high IGF-I group had shorter reaction times on the easy items. The high IGF-I group showed a significantly greater increase in cerebral blood flow in the left premotor cortex (easy items) and left dorsolateral prefrontal cortex (difficult items) compared to the low IGF-I group. It is concluded that elderly with high IGF-I levels are capable of faster working memory performance and increased recruitment of task-associated prefrontal regions.
Pituitary Resistin Gene Expression Is Upregulated in vitro and in vivo by Dexamethasone but Is Unaffected by Rosiglitazone
Authors: Brown Russell , Wiesner Glen , Ur Ehud , Wilkinson Michael
Published: April 2005

A physiological role for the adipose-derived hormone, resistin, remains unsolved and its putative involvement in insulin resistance is largely controversial. Like leptin and other adipokines, we detected resistin in the rodent hypothalamic-pituitary system. In addition, the pituitary corticotrope cell line, AtT20, is also a source of resistin. These data suggested that resistin could be involved in diverse physiological processes in non-adipose tissue. Initial studies indicated that pituitary resistin gene expression was regulated in a nutritional (fed > fasted), age- (young > old) and gender-specific manner (male > female). In the present work we hypothesized that pituitary resistin expression should be regulated through signalling pathways similar to those reported for adipose tissue. For example, dexamethasone (DEX) potently stimulates production of resistin in murine adipose tissue, whereas thiazolidinediones such as rosiglitazone (ROSI), acting via peroxisome proliferator-activated receptor (PPAR)γ, reportedly inhibit or stimulate resistin expression. Using quantitative real-time RT-PCR we determined that injection of DEX (10 and 50 µg) yielded 7- and 9-fold increases in pituitary resistin gene expression in prepubertal, but not adult mice. In addition, adrenalectomy attenuated pituitary resistin gene expression, which was restored by DEX (10 µg). In AtT20 cells, exposure to corticosterone (10–7 and 10–6M; 24 h) and DEX (10–9–10–6M) stimulated resistin mRNA more than 65% (p < 0.05) and 115% (p < 0.0001), respectively. In contrast, ROSI, injected (5 and 20 mg/kg s.c. for 14 days) or given orally (3 mg/kg/day to 10 mg/kg/day for up to 7 weeks), failed to alter pituitary resistin gene expression in healthy male CD1 mice. Treatment of AtT20 cells with ROSI (10–5–10–10M; 24 h or 96 h) or the PPARγ agonist GW 1929 (10–9 and 10–5M; 24 h) had no effect on resistin mRNA. The PPARγ antagonist GW 9662 (10–6 and 10–5M) was also ineffective. In conclusion, pituitary resistin mRNA levels are robustly stimulated by corticosteroids, particularly at the time of puberty. This is consistent with our previous suggestion that resistin may be involved in maturation of the hypothalamic-pituitary axis. In contrast, pituitary resistin gene expression appears to be PPARγ-independent and therefore different from the situation in adipose tissue.
Insulin Affects the Neuronal Response in the Medial Temporal Lobe in Humans
Authors: Rotte Michael , Baerecke Christine , Pottag Gesine , Klose Silke , Kanneberg Edgar , Heinze Hans-Jochen , Lehnert Hendrik
Published: April 2005

In recent years, clear evidence has accumulated that insulin affects central nervous functions. Besides controlling metabolic processes such as energy homeostasis by the regulation of food intake through hypothalamic receptors, the peptide hormone also appears to be capable of modulating cognitive functions. Experimental and clinical evidence for insulin supports effects on learning and memory. This study explores the impact of insulin on neuronal activity using a picture encoding task in a functional magnetic resonance imaging approach. Ten subjects performed two independent scanning sessions, each session divided into one part of four baseline runs and a second part of four runs during either insulin or saline was infused. A hyperinsulinemic- euglycemic clamp technique was applied to keep the blood glucose concentrations normal during insulin infusion. Contrast images between the two parts revealed identical activation patterns during baseline and saline conditions while during the insulin condition a higher level of activation was detected within the fusiform gyrus in both hemispheres. Shorter reaction times during the insulin condition underlined the cognitive benefit. For the first time, we were able to demonstrate that insulin enhances neuronal activity within the medio-temporal lobe and increased performance in humans under in-vivo conditions.
Cardiovascular Risk Profile and Type of Alcohol Beverage Consumption: A Population-Based Study
Authors: Schröder Helmut , Ferrández Olivia , Jimenez Conde Jordi , Sánchez-Font Albert , Marrugat Jaume
Published: April 2005

Aims: To determine the association between several cardiovascular risk factors with total alcohol and types of alcoholic beverage consumption. Methods: The subjects were Spanish men (n = 2,383) and women (n = 2,535) aged 25–74 years who were examined in 1994–1995 and 1999–2000, in two population-based cross-sectional surveys in the north-east of Spain (Gerona). Information of total amount and type of alcohol consumption, educational level, smoking, leisure-time physical, antihypertensive and hyperlipidemic drug treatment was obtained through structured questionnaires. The cardiovascular risk factors total cholesterol, HDL cholesterol, triglycerides, fasting glucose, fibrinogen, lipoprotein (a), heart rate and systolic and diastolic blood pressures were determined. Results: Men consumed significantly more alcohol than women (19.5 vs. 4.5 g/day, respectively) and the prevalence of elevated alcohol consumption (>2 glasses of wine/day) also was higher in men (35.3%) than women (3.5%). Total alcohol intake was significantly related with HDL cholesterol and fibrinogen improvements in both genders. In contrast, total cholesterol, triglycerides, heart rate, and systolic and diastolic blood pressures were directly and significantly (p < 0.05) associated with total alcohol consumption in men but not in women. Wine drinking, particularly in women, was associated with a healthy cardiovascular risk profile. Most of the observed significant associations between type of alcohol beverage and CHD risk factors disappeared after controlling for total alcohol consumption and other confounders. Conclusions: Alcohol consumption was favorably related to the cardiovascular risk profile in women but not in men. The relationship of alcohol beverages seems to be mediated by the total alcohol content rather than by the type of beverage itself.
Membrane Biocompatibility Does Not Affect Whole Body Protein Metabolism during Dialysis
Authors: Veeneman Jorden M. , Kingma Hermi A. , Stellaard Frans , de Jong Paul E. , Reijngoud Dirk-Jan , Huisman Roel M.
Published: April 2005

Background: Protein-calorie malnutrition is present in 30–50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to incompatibility of the dialyzer during the dialysis session. Methods: Five patients were dialyzed during 2 periods of 3 weeks (cross-over) with either a single-use low-flux polysulfone or cellulose triacetate (biocompatible) or a single-use cuprophan (bio-incompatible) membrane. As a measure of whole body protein metabolism, a primed constant infusion of L-[1-13C]-valine was used during a 4-hour dialysis session. Results: Cuprophan was a more powerful activator of the complement system than other membranes. Protein metabolism parameters during both study protocols were not different and resulted in the same protein balance during polysulfone/cellulose triacetate (–15 ± 3) and cuprophan (–13 ± 2 µmol/kg/h) dialysis. Conclusion: In stable hemodialysis patients with no apparent complications, protein metabolism during dialysis is not affected by the compatibility of the dialysis membrane.