Neurotrophic effects of GM1 ganglioside, NGF, and FGF2 on canine dorsal root ganglia neurons in vitro.

Dogs share many chronic morbidities with humans and thus represent a powerful model for translational research. In comparison to rodents, the canine ganglioside metabolism more closely resembles the human one. Gangliosides are components of the cell plasma membrane playing a role in neuronal development, intercellular communication and cellular differentiation. The present in vitro study aimed to characterize structural and functional changes induced by GM1 ganglioside (GM1) in canine dorsal root ganglia (DRG) neurons and interactions of GM1 with nerve growth factor (NGF) and fibroblast growth factor (FGF2) using immunofluorescence for several cellular proteins including neurofilaments, synaptophysin, and cleaved caspase 3, transmission electron microscopy, and electrophysiology. GM1 supplementation resulted in increased neurite outgrowth and neuronal survival. This was also observed in DRG neurons challenged with hypoxia mimicking neurodegenerative conditions due to disruptions of energy homeostasis. Immunofluorescence indicated an impact of GM1 on neurofilament phosphorylation, axonal transport, and synaptogenesis. An increased number of multivesicular bodies in GM1 treated neurons suggested metabolic changes. Electrophysiological changes induced by GM1 indicated an increased neuronal excitability. Summarized, GM1 has neurotrophic and neuroprotective effects on canine DRG neurons and induces functional changes. However, further studies are needed to clarify the therapeutic value of gangliosides in neurodegenerative diseases.

Drospirenone plus estradiol and the risk of serious cardiovascular events in postmenopausal women.

OBJECTIVES: To compare incidence rates of serious cardiovascular events, particularly arterial thromboembolic events (ATE), in users of hormone replacement therapy (HRT), particularly oral continuous combined preparations. METHODS: Prospective, controlled cohort study with four arms: women using (1) drospirenone (DRSP)/estradiol, (2) other oral continuous combined HRT (HRTcc), (3) all other oral HRTs, and (4) non-oral HRT. The study population consisted of women aged 40+ years in seven European countries who were new users of HRT at the time of inclusion. All patient-reported outcomes of interest were validated by the treating physicians. A multifaceted, four-level follow-up procedure ensured low loss to follow-up rates. The final analysis is based on Cox regression models comparing the cohorts. RESULTS: In total, 30 597 women were recruited by 1052 study centers. Follow-up reflects 101 715 woman-years of observation. Loss to follow-up was about 2.8%. Risk estimates for general serious adverse events were similar for all cohorts. Incidence rates for serious cardiovascular events were 98.4 (DRSP/estradiol) and 169.7 (HRTcc) per 10 000 woman-years. The corresponding incidence rates for ATE were 10.9 and 29.7 events per 10 000 woman-years with an adjusted hazard ratio of 0.5 (95% confidence interval 0.3-0.8). The initiation rate for antihypertensive treatment after start of HRT was substantially lower for women using DRSP/estradiol compared to the other cohorts. CONCLUSIONS: DRSP/estradiol is associated with general health risks similar to other oral and non-oral HRT but is probably associated with lower ATE risk. CLINICAL TRIAL REGISTRATION: NCT00214903, US National Library of Medicine.

Decreased IL-10(+) regulatory B cells (Bregs) in lupus nephritis patients.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell-dependent autoantibody production. Recently, a new B-cell subset was discovered that has a regulatory capacity. The aim of this study was to analyse regulatory B cells (Bregs) in SLE patients. METHOD: Peripheral mononuclear blood cells (PBMCs) of 34 SLE patients fulfilling the American College of Rheumatology (ACR) criteria for SLE and 21 healthy controls (HC) were included. PBMCs were stained for CD19, CD24, and CD38 and analysed by flow cytometry. In vitro stimulated PBMCs with CpG and restimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin were investigated for IL-10(+) Bregs . RESULTS: The percentages of circulating CD19(+)CD24(hi)CD38(hi) cells in HC were not different those in from SLE patients. The percentages of IL-10(+) Bregs were significantly decreased in SLE patients, in particular those with lupus nephritis (LN), compared to HC. The proportion was independent of disease activity. CONCLUSIONS: This is the first study to demonstrate a decrease in IL-10-producing B cells in LN patients compared to HC, reflecting an impaired regulatory function.

The compactEASIE is a feasible training model for endoscopic novices: a prospective randomised trial.

BACKGROUND: The objective benefit of a training using the compact Erlangen Active Simulator for Interventional Endoscopy-simulator was demonstrated in two prospective educational trials (New York, France). The present study analysed whether endoscopic novices are able to reach a comparable level of endoscopic skills as in the above-described projects. METHODS: Twenty-seven endoscopic novices (medical students, first year residents) were enrolled in this prospective, randomised trial. The compact Erlangen Active Simulator for Interventional Endoscopy-simulator with an upper GI-organ package and blood perfusion system was used as a training tool. Basic evaluation of endoscopic skills was performed after a practical and theoretical course in diagnostic upper GI endoscopy followed by a stratified randomisation according to the rating in endoscopic skills into intensive (n=14) and control group (n=13). The intensive group was trained 12 times every second week over 7 months in 4 endoscopic disciplines (manual skills, injection therapy, haemoclip, band ligation) by skilled endoscopist (three trainees/simulator). Assessment was performed (single steps/overall) using an analogue scale from 1 to 10 (1=worst, 10=optimal performance) by expert tutors. The control group was not trained. Blinded final evaluation of all participants was performed in January 2003. RESULTS: We observed in all techniques applied a significant improvement of endoscopic skills and of the performance time in the intensive group compared to the control group (p<0.001). The comparison with the previous projects showed that the intensively trained novices achieved comparable levels of performance to the GI fellows in the New York and France Project (at least 80% of the median score in three out of four techniques). CONCLUSION: Endoscopic novices acquired notable skills in interventional endoscopy in the simulator by an intensive, periodical training using the compactEASIE.

Can results of the Aging Males' Symptoms (AMS) scale predict those of screening scales for androgen deficiency?

INTRODUCTION: The Aging Male Symptoms' (AMS) scale was designed as a health-related quality of life (QoL) scale and standardized as a self-administered scale, first, to assess symptoms of aging (independent from those which are disease-related) between groups of males under different conditions, second, to evaluate the severity of symptoms/QoL over time, and, third, to measure changes pre- and post-androgen replacement therapy. The scale is in widespread use (17 languages currently available) and a recent review of methodological data documented good psychometric characteristics and ability as a clinical utility. This paper describes test characteristics of the AMS (positive and negative predictive values), taking two internationally established and published screening scales for androgen deficiency as the available standard. METHOD: A sample of 150 German males aged 40-69 years completed the AMS scale and two screening scales for androgen deficiency: the ADAM scale of Morley and colleagues and the screener of Smith and colleagues. The technique of a computer-assisted telephone interview was applied. RESULT: The comparison of the AMS with the two screening instruments for androgen deficiency showed sufficiently good compatibility despite conceptual differences. The AMS scale sufficiently predicted the results of the two screening instruments. A positive predictive value of 92% and a negative predictive value of 50% were found regarding the ADAM scale. The respective figures regarding Smith's screener were 65% and 49% for positive and negative predictive values, respectively. CONCLUSION: The AMS scale obviously measures a similar phenomenon as the two established and widely used screeners for androgen deficiency, although it was not developed as a screening instrument.

Liver transplantation for hepatic and neurological Wilson's disease.

Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.

[Reliability of the Menopause Rating Scale (MRS): Investigation in the German population]. / Reliabilität der Menopause-Rating-Skala (MRS) - Untersuchung für die deutsche Bevölkerung.

The Menopause Rating Scale (MRS) is a well accepted instrument to measure the severity of menopausal symptoms. As yet, however, investigations had not specifically been directed towards short-term test-retest reliability of the scale. The MRS was twice applied in a random sample of 45-65 years aged women of the German Cohort Study of Women's Health with a distance between the measurements of 14 days. The response rate in the sample was 70 %. The correlation coefficient (Pearson) of the sum-score of the two measurements was r = 0.82. The high repeatability of the test results confirms our clinical experience and emphasizes excellent practical applicability. The MRS can be recommended for the clinical practice as a reliable scale both for the measurement and long-term surveillance of menopausal complaint dynamics.

[Trends of OC use 1980-1999 in a German cohort of women]. / Trend der OC-Nutzung in einer Deutschen Frauen-Kohorte 1980-1999 - Ergebnisse der Deutschen Kohortenstudie zur Frauengesundheit.

INTRODUCTION: There is no doubt, oral contraceptives are a safe, reversible and commonly used method of contraception. Ever use is about 80 % in developed countries and current use of OCs about 40 %. Almost all information about prevalence of OC use came from cross-sectional studies and did not distinguish between high- and low-dose OCs. This paper deals with the prevalence of OC use as it was observed during lifetime of a large cohort of German women by calendar year and estrogen content. METHODS: The prevalence of OC use between 1980 to 1999 was analysed on occasion of an interim analysis of the German cohort study on women's health. This analysis is based on more than 10 000 women with about 390 000 women-years of observation. RESULTS: The proportion of women under the age of 50, that ever used OCs, increased steeply from 1980, i. e. from 62 % (1980) to about 90 % from 1996 onward. The proportion of current users in a given calendar year rose from 44 % (1980) to 49 % (1991-95) and dropped after the "pill crisis 1995". The percentage of current users who used high-estrogen-dose OCs dropped from 32 % (1980) to 5 % (1999). In contrast, the percentage of users of low-dose OCs of the 2nd generation steeply increased as was the percentage of users of the 3rd generation pills, however the latter dropped after 1995. CONCLUSION: The high acceptance of oral contraceptives despite many "pill crises" underlines the continuously high appreciation of their efficacy on the one hand, but underscores also the high responsibility of physicians and industry concerning surveillance or reduction of discussed side effects.

Occupational exposure and liver cancer in women: results of the Multicentre International Liver Tumour Study (MILTS).

The association of occupational variables and hepatocellular cancer (HCC) is discussed with particular reference to women, as little research has been undertaken on their behalf. This paper reports the results of an international case-control study concerning women and involves 317 cases of HCC and 1789 controls. Working in the chemical industry was shown to have only a marginally significant risk associated with HCC: adjusted odds ratio (OR) and 95% confidence interval 2.37 (1.04-5.41). Other non-significantly elevated ORs were observed in the pharmaceutical, plastics, PVC-producing, farming and butchery industries. Little consistency was found among the risk estimates for HCC, based on three different analytical approaches. None of the analyses showed a linear trend of risk with increasing duration of exposure. However, the numbers of exposed cases and controls were small for many of the occupations and therefore the study power and precision were low. We failed to find important and consistent evidence for a relationship between HCC in women and occupational variables. However, even weak evidence of occupational risk warrants careful consideration in future studies.

Current development of the human and environmental contamination in the Bryansk-Gomel Spot after the Chernobyl accident.

Up to 1991, it was assumed that after the Chernobyl accident in 1986 the time development of radioactive contamination with regard to environment, foodstuff, and man would decrease due to migration processes in the soil, radioactive decay, and protective measures. This assumption was confirmed by all measurements in the first few years after the accident. Since 1991, however, a change in this development has been observed, as many measurements show stagnation or in some cases even an increase of foodstuff and human contamination. If normalised to an average local ground contamination, only a few groups of foodstuffs (e.g., potatoes) show a slight decrease in radioactivity. In this paper, the time development of radioactive contamination in the Bryansk-Gomel Spot on the basis of measurements since 1991 is presented. The consequences for long-term dose assessment are discussed.

Monitoring of radioiodine in nuclear medical therapy.

The composition of the radioiodine species that is released in a hospital by nuclear medical therapy is investigated. More than 90% are found to be organic iodine. This leads to a reduction of the calculated radiation exposure in the environment by more than a factor of ten with regard to pure elemental iodine releases. The organic iodine is not formed by chemical reactions in the air of the rooms butoriginates in patients, who are treated with 131I. Effective half-lives and release factors for exhalation were determined by monitoring the exhaled air of the patients.