[Proximal myopathy and fulminant heart failure in a 57 year-old female patient with lupus erythematosus]. / Proximale Muskelschwäche und fulminante Herzinsuffizienz bei einer 57-jährigen Patientin mit Lupus erythematodes.

A case report is presented of fulminant hydroxychloroquine-induced cardiomyopathy in a 57 year-old female patient with a long history of systemic lupus erythematosus. Diagnosis was established based on clinical findings, imaging (echocardiography and cardiac magnetic resonance imaging) as well as endomyocardial biopsy. Despite immediate discontinuation of the medication, the patient died from heart failure within a few days. Since the rare adverse effect described here might be reversible, early diagnosis and discontinuation of hydroxychloroquine are crucial for the prognosis of these patients.

[Undergraduate Medical Students "On Call" to Assist in Theatre: Analysis of the Financial Aspects and a Mixed-Method Study Exploring Their Motives for Working]. / Studentische Hilfskräfte im "Operativen Rufdienst": Mixed-Method-Studie zur Analyse des finanziellen Aspekts und der Motive der Studierenden.

Background/Purpose: Surgical patient care has grown in complexity, as hospital workload has continuously increased. We therefore established a pool of "undergraduate medical students on call" to assist in the theatre outside working hours. We aimed to recruit talented students to reduce the burden on physicians and to motivate students into entering surgery. Methods: An exploratory mixed-method study was performed. In a qualitative study, guided interviews were conducted with five students about their reasons for working in the theatre and the results were used to construct an online questionnaire using EvaSys®. This was presented to 16 current and former students in a subsequent quantitative study. Furthermore, the cost of student employment was calculated and compared with physicians' salaries. Results: In 2013 and 2014, 8-9 students worked a total of 1063 and 1211 hours in the theatre, respectively. The difference in salaries between the students and surgical residents was € 28.37 per hour. We calculated that the annual savings were approximately € 60,000. When questioned on their motives during the interview, only a few students emphasised the financial aspects, whereas the majority emphasised the gain in experience. The analysis was based on comparison of the mean values (online survey) with a 4-point Likert scale (1 = high acceptance; 4 = no acceptance). We defined the motives with a mean ≤ 1.3 as primary. Based on this selection, gathering experience, fun/enjoyment, interest in surgery, and the change from studying were considered as distinct motives. In the interviews, students clearly pointed out that teaching and learning opportunities in the theatre were not commonly taken advantage of and that interaction with the surgeons should be improved. Conclusion: Students actively chose to work as assistants in the theatre, for a variety of motives. The financial aspects were subordinate. The concept of students assisting in the theatre is favourable for both employers and students. However, the results also reveal that there is room for improvement in the implementation of the concept.

[Recruiting and Personal Development in Surgical Departments of Large Referral Centers - Current Practice and Options for Improvement from Industry and Service Business]. / Personalgewinnung und -entwicklung in viszeralchirurgischen Kliniken von Großkrankenhäusern ­ derzeitiger Stand und Möglichkeiten der Optimierung aus Industrie und Dienstleistungsgewerbe.

Background Cut-throat competition, cost pressure, generation Y, shortage of qualified staff and feminisation influence human resources management in visceral surgery. The assessment of the current situation by chief surgeons (CS) as well as proof of transferability of strategies from industry and service business (ISB) have not yet been investigated. Material and Methods The CS of university hospitals and large referral centres (> 800 beds) were interviewed (n = 100) on the basis of a standardised questionnaire including 43 items. Closed questions were designed with a 5-point Likert scale and their analysis was presented as means (MW) and standard deviations (±). Ten human resources manager (HMR) of ISB were invited to participate in 45-minute telephone interviews. Results Thirty-seven CS participated in the survey, 15 of whom were full professors. Unsolicited applications (100%), job advertisements (78%) and direct approaches to final year students (78%) were the most common ways of recruitment. Only 17% of CS used a standardised form for preparation. Professional expertise (MW 2.2 ± 0.9), social skills (MW 1.9 ± 0.6) and excellent German language skills (MW 1.8 ± 0.8) were named as important qualifications for employment, while references and certificates were regarded as being less important (MW 3.2 ± 0.9). Personal development was regarded as important (MW 1.1 ± 0.2), but a defined period for residency was not guaranteed (MW 3.0 ± 1.5). Transparent selection criteria for career opportunities (MW 2.5 ± 1.1) and different career models (MW 2.7 ± 1.2) were only rarely available. Six HRM participated in the interviews. Active head-hunting (75%), Internet platforms (75%), presentations at conferences (75%), as well as hiring trainees (50%), job advertisements (50%) and social media (50%) were established options to find qualified employees. Professional and management careers were often separate career paths, while social expertise was regarded as being crucial for filling management positions. Conclusion In visceral surgery, unsolicited applications, job advertisements and direct approaches to final year students are the most common ways for recruitment. Diversified professional and management careers are not yet established. Recruiting strategies that are successful in ISB - such as active scouting and use of social media - should be evaluated for visceral surgery, as well as diversified career models.

Can We Use Blood Biomarkers as Entry Criteria and for Monitoring Drug Treatment Effects in Clinical Trials? A Report from the EU/US CTAD Task Force.

In randomized clinical trials (RCTs) for Alzheimer's Disease (AD), cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers are currently used for the detection and monitoring of AD pathological features. The use of less resource-intensive plasma biomarkers could decrease the burden to study volunteers and limit costs and time for study enrollment. Blood-based markers (BBMs) could thus play an important role in improving the design and the conduct of RCTs on AD. It remains to be determined if the data available on BBMs are strong enough to replace CSF and PET biomarkers as entry criteria and monitoring tools in RCTs.

Chromocolonoscopy detects more adenomas than white light colonoscopy or narrow band imaging colonoscopy in hereditary nonpolyposis colorectal cancer screening.

BACKGROUND AND STUDY AIMS: Individuals carrying germline mutations in one of the genes responsible for hereditary nonpolyposis colon cancer (HNPCC) have a lifetime risk of up to 80 % of developing colorectal cancer. As there is evidence for a higher incidence of flat adenomatous precursors and because an accelerated adenoma-carcinoma sequence has been postulated for these patients, early detection of these lesions is essential. It was the aim of the present study to assess the detection rate of polypoid lesions by comparing chromocolonoscopy with standard white light colonoscopy and narrow-band imaging (NBI) colonoscopy. PATIENTS AND METHODS: 109 patients were included (98 with a functionally relevant mutation in a mismatch repair gene, 11 fulfilling the strict Amsterdam criteria). In 47 patients, standard colonoscopy was followed by chromocolonoscopy with indigo carmine. In 62 patients, NBI was performed first followed by chromocolonoscopy. RESULTS: A total of 128 hyperplastic and 52 adenomatous lesions were detected. In the first series, 0.5 lesions/patient were identified by standard colonoscopy and 1.5 lesions/patient by chromocolonoscopy ( P < 0.001). In the second series, 0.7 lesions/patient were detected by NBI colonoscopy and 1.8 lesions/patient by chromocolonoscopy ( P = 0.01). At least one adenoma was detected in 15 % of patients by both standard and NBI colonoscopy compared with 28 % of patients by chromocolonoscopy. CONCLUSION: According to this study, chromocolonoscopy detects significantly more hyperplastic and, in particular, adenomatous lesions than standard white light colonoscopy or NBI.

Percutaneous endoscopic jejunostomy and jejunal extension tube through percutaneous endoscopic gastrostomy: a retrospective analysis of success, complications and outcome.

BACKGROUND: Percutaneous access to the jejunum is an important approach if gastrostomy feeding is not possible. OBJECTIVE: To analyze success, short- and long-term complications (STCs, LTCs) in patients with percutaneous endoscopic jejunostomy (PEJ) and jejunal access through percutaneous endoscopic gastrostomy (Jet-PEG). METHODS: A retrospective analysis of endoscopically placed PEJs and Jet-PEGs. Success rates, mortality, STCs and LTCs were investigated for risk factors comprising demographic data, underlying disease, previous surgery and experience of the endoscopist. RESULTS: 205 PEJ and 58 Jet-PEG placements were included in the study. PEJs and Jet-PEGs were successfully placed in 65.4 and 89.7%, respectively. Billroth II surgery predisposed in favor of a significantly higher success rate for PEJ placement (p = 0.014, OR = 2.27). Inexperienced examiners have a significantly (p = 0.040) lower success rate for tube insertion than examiners with a medium level of experience. STCs and LTCs occurred evenly in PEJ and Jet-PEG patients. Dislocation of the tube occurred significantly more frequently in Jet-PEG patients (33.3%, p = 0.005). Aspiration was most common for bedridden patients. CONCLUSION: PEJ has a significantly lower success rate for insertions, but fewer LTCs. The experience of the endoscopist correlates with the success rate of tube insertion.

Gender-based differences in drug prescription: relation to adverse drug reactions.

BACKGROUND/AIM: The female gender appears to suffer from more adverse drug reactions (ADRs) than the male gender. So far, there has been no epidemiologic study analyzing gender-based differences in drug prescribing and its ADR risks. The aim of the present study was to establish a drug risk stratification adjusted to age, number of prescriptions and drug classes with respect to gender differences based on intensive data acquisition methods. METHOD: A prospective multicenter study was conducted in several departments in Germany and Israel (pediatrics, medicine and geriatrics) enclosing 2,371 inpatients. RESULTS: A total of 25,532 drug prescriptions during hospitalization were evaluated. At least 1 ADR was found in 774 patients (32.6%). Drugs for the cardiovascular system, nervous system, alimentary tract and musculoskeletal system were prescribed most often in females. The following drug classes led significantly more often to ADRs in women as compared to men: alimentary tract (OR 0.5; p = 0.0002), cardiovascular system (OR 0.72; p = 0.0140), musculoskeletal system (OR 0.31; p = 0.0004) and nervous system (OR 0.62; p = 0.0023). After adjustment to age, total number of prescriptions and drug class, only anti-infectives (antibacterials) and musculoskeletal system (anti-inflammatory) drugs stand out as causing more ADRs in women. CONCLUSION: Antibacterials and anti-inflammatory agents cause more ADRs in females as compared to males.

Women encounter ADRs more often than do men.

BACKGROUND: Several publications indicate that the female gender experiences a higher incidence of adverse drug reactions (ADRs) than does the male gender. The reasons, however, remain unclear. Gender-specific differences in the pharmacokinetic and pharmacodynamic behaviour of drugs could not be identified as an explanation. The aim of this study was to analyse ADR risk with respect to gender, age and number of prescribed drugs. METHODS: A prospective multicenter study based on intensive pharmacovigilance was conducted. Information on patient characteristics and evaluated ADRs was stored in a pharmacovigilance database--KLASSE. RESULTS: In 2,371 patients (1,012 female subjects), 25,532 drugs were prescribed. In 782 patients, at least one ADR was found. A multivariate regression analysis adjusting for age, body mass index (BMI) and number of prescribed drugs showed a significant influence of female gender on the risk of encountering ADRs [odds ratio (OR) 1.596, confidence interval (CI) 1.31-1.94; p < 0.0001). Dose-related ADRs (51.8%) were the dominant type in female subjects. Comparing system organ classes of the World Health Organisation (SOC-WHO), cardiovascular (CV) ADRs were particularly frequent in female subjects (OR 1.92, CI 1.15-3.19; p = 0.012). CONCLUSION: Our data confirm the higher risk of ADRs among female subjects compared with a male cohort. Several explanations were investigated. No single risk factor could be identified.

Therapy of hepatocellular carcinoma with iodine-131-lipiodol. Results in a large German cohort.

AIM: To evaluate the efficacy and tolerance of iodine-131-lipiodol ((131)I-lipiodol) for hepatocellular carcinoma (HCC) in German long term patients and comparison with medically treated controls. PATIENTS, METHODS: 38 courses of intra-arterial (131)I-lipiodol therapy with a total activity up to 6.7 GBq were performed in 18 patients with HCC (6 with portal vein thrombosis). Liver and tumour volume and lipiodol deposition were measured by computed tomography and (131)I activity by scintigraphy. Therapeutic efficacy was determined by tumour volume change and matched-pairs analysis in comparison to medically (i.e. tamoxifen or medical support) treated patients. RESULTS: Tumour volume decreased in 20/32 index nodules (63%) after the first course. Repeated therapy frequently resulted in further tumour reduction. Overall response to treatment was partial in 11 nodules, minor response in 4 nodules, and disease was stable in 12 and progressive in 5. Significant response was associated with pretherapeutic nodule volume up to 150 ml (diameter of 6.6 cm). Survival rate after 3, 6, 9, 12, 24 and 36 months was 78, 61, 50, 39, 17, and 6%. Matched-pairs analysis of survival revealed (131)I-lipiodol to be superior to medical treatment. The most important side effect was a pancreatitis-like syndrome whereas overall tolerance was good. CONCLUSION: The long term results confirm that HCC therapy with (131)I-lipiodol is effective and probably superior to medical treatment. Tumour nodules of up to 6 cm diameter are well suited for this therapy even in the presence of portal vein thrombosis.

The attributable risk in a multifactorial situation--evaluation of different methods of partitioning.

OBJECTIVES: Different approaches to partition the attributable risk into exposure-specific components are methodologically evaluated. METHODS: Two methods of partitioning the attributable risk in a multifactorial situation have been suggested. One is based on a solution adopted from game theory, the Shapley value, whereas the other recently suggested approach uses a heuristically motivated proportional weighting scheme. These two concepts are reviewed and compared in a situation with three exposure factors. A hypothetical numerical example is discussed illustrating differences in the case of complex interaction structures. RESULTS: The two methods are found to differ in two critical features that affect the outcome of partitioning: i) including or ignoring the full interaction structure between exposure factors involved in the partitioning, ii) using an equal or proportional weighting scheme for the marginal excess risks of the exposures. As a result, not only the individual partial attributable risks for the exposure factors may be quantitatively different between the methods, but also their ranking depends on the partitioning approach. CONCLUSIONS: The epidemiologic properties of the partitioning procedure based on the Shapley value are known and fit to the needs of epidemiologic applications. The alternative approach recently suggested can lead to considerably different results. As long as its epidemiologic properties are not fully understood, the traditional partitioning method should be given preference in practical applications.

Effect of ethanol on cyclic AMP levels in intact PC12 cells.

Two subclones of the rat pheochromocytoma cell line, PC12, were used to compare the effects of ethanol on adenylate cyclase activity in isolated membranes with its effects on cyclic AMP accumulation in intact cells. Consistent with previous reports, ethanol increased basal and 2-chloroadenosine-stimulated adenylate cyclase activity in isolated membrane preparations from both subclones. However, ethanol had opposite effects on agonist-stimulated cyclic AMP accumulation in intact cells of the two subclones, enhancing accumulation in one subclone, and inhibiting it in the other. The inhibition of cyclic AMP accumulation did not result from stimulation of phosphodiesterase activity, activation of the inhibitory guanyl nucleotide regulatory protein, Gi, or stimulation of protein kinase C. The results indicate that extrapolation of the effects of ethanol from one cell type to another, or from in vitro to in vivo systems, may be complicated by the interaction of ethanol with regulatory processes that influence second messenger systems, and can differ in various types of intact cells.

Mood and the use of scripts: does a happy mood really lead to mindlessness?

The authors tested whether happy moods increase, and sad moods decrease, reliance on general knowledge structures. Participants in happy, neutral, or sad moods listened to a "going-out-for-dinner" story. Happy participants made more intrusion errors in recognition than did sad participants, with neutral mood participants falling in between (Experiments 1 and 2). Happy participants outperformed sad ones when they performed a secondary task while listening to the story (Experiment 2), but only when the amount of script-inconsistent information was small (Experiment 3). This pattern of findings indicates higher reliance on general knowledge structures under happy rather than sad moods. It is incompatible with the assumption that happy moods decrease either cognitive capacity or processing motivation in general, which would predict impaired secondary-task performance.

Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma.

AIM: To conduct a cohort study of 101 patients with hepatocellular carcinoma (HCC) presenting to a tertiary care medical referral center in Germany between 1997 and 1999. METHODS AND RESULTS: Data were retrospectively analyzed by chart review. In 95 cases (72 males and 23 females) sufficient data were available for analysis. Twenty five (29%) of 85 patients were HBsAg or anti HBc positive, 21/85 (25%) were anti HCV positive, and 6/85 (7%) were positive for both HBV and HCV-markers. Age was significantly lower in HBV positive patients than in the other two groups. Thirty one (34%) of 90 patients had histories of alcohol abuse. In 79/94 (84%) patients, cirrhosis was diagnosed. Of these cirrhotic patients, 29/79 (37%) belonged to Child Pugh's group (CHILD) A, 32/79 (40%) to CHILD B, and 18/79 (23%) to CHILD C. AFP was elevated in 61/91 (67%) patients. A single tumor nodule was found in 38/94 (40%), more than one nodule in 31/94 (34%), and 25/94 (26%) had a diffusely infiltrating tumor, i.e. the tumor margins could not be seen on imaging procedures. Portal vein thrombosis was present in 19/94 (20%). Imaging data consistent with lymph node metastases were found in 10/92 (11%), while distant metastases were found in 8/93 (9%). According to Okuda 28/94 (30%) were grouped to stage I, 53/94 (56%) were grouped to stage II, and 13/94 (14%) were grouped to stage II. Survival data were available for 83 patients. The Kaplan-Meier estimate for median survival was 8 4 months. Factors influencing survival were the Okuda score, the presence of portal vein thrombosis, and the presence of ascites. The presence of non complicated liver cirrhosis by itself, distant metastases, or infection with hepatitis viruses did not influence survival. AFP positivity by itself did not influence survival, though patients with an AFP value greater than 100 microg/L did experience shortened survival. Treatment besides tamoxifen or supportive care was associated with prolonged survival. The influence of therapy on survival was most pronounced in Okuda stage II patients. There was longer survival in those Okuda stage II patients who were treated with percutaneous ethanol injection. CONCLUSION: Even in a low incidence area such as Germany, the majority of HCC is caused by viral hepatitis and therefore potentially preventable. Reflecting the high proportion of advanced stage tumors in our patients, the median survival was poor. Patients who received active therapy had a longer survival.

Ethanol and the NMDA receptor.

The actions of glutamate, the major excitatory amino acid in the CNS, are mediated by three receptor subtypes: kainate, quisqualate and N-methyl-D-aspartate (NMDA) receptors. Ethanol, in vitro, is a potent and selective inhibitor of the actions of agonists at the NMDA receptor. Following chronic ethanol ingestion, the number of NMDA receptor-ion channel complexes in certain brain areas is increased. This increase may contribute to the generation of ethanol withdrawal seizures, since administration of an NMDA receptor antagonist can reduce these seizures. The results suggest that certain acute behavioral effects of ethanol, such as effects on memory, as well as certain aspects of ethanol withdrawal, may involve the NMDA receptor.

Why do some apheresis donors donate blood just once?

BACKGROUND AND OBJECTIVES: More knowledge about the reasons for non-return of blood donors (BD) would enable blood donation services (BDS) to improve the efficacy of recruitment and retention programmes. We interviewed returning (RBD) and non-returning apheresis BDs (NRBD) of our university hospital-based BDS. MATERIALS AND METHODS: A questionnaire was sent to 1218 individuals who passed the initial health check with no more than one subsequent blood donation. A similar questionnaire was answered by 235 randomly incoming RBDs. We asked for age, sex, profession, education level, motives to donate blood and, if applicable, reasons for non-return. These data were compared between NRBDs and RBDs and were analysed in relationship to the reasons for non-return. RESULTS: We received 267 answered questionnaires (21.9%). As 32 individuals indicated that they had been permanently deferred and 47 BDs had donated blood elsewhere, 188 NRBDs remained for further analysis. We found more women than men among NRBDs. Medical professions were less likely to return than students and trainees. Individuals motivated by personal experience, remuneration or a free health check were more likely to return than others. Whereas logistic reasons were of highest relevance for non-return in general, women indicated anxiety of blood donation as reason for non-return more often than men. CONCLUSION: Reducing women's anxiety of blood donation, reminding medical professions more intensively on blood donation and appealing to personal experience or a free health check may be the most promising approaches to increase BDs' return rates.

Biliary metal stents and air embolism: a note of caution.

Metal stents are a valuable treatment modality for patients with biliary obstruction. However, we present here two patients whose cases may serve as a warning about an unusual complication associated with these stents. We encountered this complication after endoscopic retrograde cholangiography for obstructed metal biliary stents. The first patient, an 87-year-old man with a benign biliary stricture, failed to regain consciousness after clearing of his stent using a Dormia basket and balloon catheter. Cerebral air embolism was diagnosed on cerebral computed tomography, and transesophageal echocardiography revealed a patent foramen ovale as a precipitating factor for paradoxical air embolism. He survived and was discharged with a residual hemiparesis. In the second patient, a 54-year-old man who had a history of a Billroth II operation and chronic pancreatitis and who had a portal cavernoma with biliary obstruction due to collateral veins, electromechanical dissociation complicated the balloon-catheter stent revision. Echocardiography performed during cardiopulmonary resuscitation showed major air embolism to the right heart. The patient died. These cases demonstrate that air may gain access to the venous system during therapeutic endoscopic procedures of this type. It is likely that the large diameter of metal stents and the potential for these stents to lacerate venous structures facilitate the entry of air into the venous circulation, an event which may have life-threatening consequences.

Increased VEGF levels induced by anti-VEGF treatment are independent of tumor burden in colorectal carcinomas in mice.

Inhibition of vascular endothelial growth factor (VEGF) by gene transfer techniques was effectively applied to control experimental tumor growth, whereas effects on systemic VEGF levels had not been investigated. Therefore, we evaluated the effect of VEGF inhibition by adenoviral-mediated gene delivery of a dominant-negative soluble fragment of FLK-1 (sFlk-1) on systemic VEGF levels, organ-specific VEGF-RNA expression and antitumor efficacy in a murine colorectal cancer (CRC) tumor model. Vector function of AdsFlk-1 was shown by Western blot analysis and transgene expression was documented over a time period of 42 days in the serum of treated mice. Although cell supernatant of CT26 cells contained considerable levels of VEGF, systemic VEGF levels in the serum of tumor-bearing mice remained unaffected. Interestingly, mice that were systemically treated with AdsFlk-1 showed a strong upraise of circulating VEGF, whereas VEGF remained at background levels in the control. Vascular endothelial growth factor was increased not only in tumor bearing but also in healthy, tumor-free mice. Vascular endothelial growth factor determination in liver tissue homogenates showed a 16.5-fold upraise in AdsFlk-1-treated animals as compared to the AdLacZ control. Consecutively, systemic small interfering RNA injection targeted against VEGF reverted elevated VEGF levels almost back to normal levels. In spite of elevated VEGF levels, AdsFlk-1 administration showed significant antitumor effects in a subcutaneous metastatic CRC tumor model. There was no significant correlation between antitumour treatment response and VEGF levels in this model. Collectively, we conclude that the systemic administration of AdsFlk-1 had significant inhibitory effects on metastatic CRC tumor growth in spite of elevated systemic VEGF levels and that VEGF serum concentrations did not correlate to tumor burden and antitumor treatment response in this model.