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Background and objectives : Rare diseases affect an estimated four million patients in Germany. Approximately 15% of the approximately 6000 to 8000 rare diseases known globally show manifestations in the dental, oral and maxillofacial regions. The present survey evaluated the knowledge and management of rare diseases and their orofacial alterations by dentists, dental specialists and oral and maxillofacial surgeons and dentists working at university hospitals for dentistry and/or oral and maxillofacial surgery. Materials and Methods: The study was designed as an anonymous cross-sectional study. Two anonymous online surveys were performed in all dentists in Germany using the open-source survey software limesurvey. The study cohorts were divided into dentists, dental specialists and oral and maxillofacial surgeons in practice, and dentists who worked in university dental and oral and maxillofacial surgery centers. The survey was performed between 1 October 2020 and 31 March 2021. Results: A total of 309 dentists and oral and maxillofacial surgeons in private practice and 18 dentists or oral and maxillofacial surgeons working at universities participated. A total of 209 (86.7%) study participants working in private practice indicated that the topic of rare diseases should be considered clinically relevant. University participants indicated that there was a lecture on rare diseases in only 7 (63.6%) cases. Only 2 (13.3%) participants reported active research on the topic in their department. Conclusions: The current knowledge on rare diseases is inadequate in suitable screening and therapy. Most of the participants believed that knowledge of rare diseases was very important for daily dental practice. The self-estimations showed that all of the participants estimated their knowledge as very good or inadequate, with a tendency in the direction of inadequate knowledge.

Many species rely on individual recognition (i.e., the use of individual signals to identify and remember a conspecific) to tune their social interactions. However, little is known about how the configuration of the sensory system may affect the perception of individual recognition signals over space. Utilizing a visual modeling approach, we quantified (1) the threshold distance between the receiver and the signaler at which individual recognition can no longer accurately occur, and (2) the regions of the head most likely to contain the individual recognition signals. We used chickens (Gallus gallus) as our study species, as they use visual individual recognition and additionally have a well-studied visual system. We took pictures of different individuals and followed a visual modeling approach considering color vision, visual acuity, and pattern processing of the receiver. We found that distance degrades the quality of information in potential individual recognition signals. We estimated that the neighbor distance at which a receiver may have difficulty recognizing a conspecific was between 0.25 and 0.30 m in chickens, which may be related to a decrease in available features of the potential signal. This signal perception threshold closely matches the recognition distance predicted by previous behavioral approaches. Additionally, we found that certain regions of the head (beak, cheek, comb, eye) may be good candidates for individual recognition signals. Overall, our findings support that recognition in chickens occurs at short distances due to constraints imposed by their visual system, which can affect the costs and benefits associated with social spacing in groups., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Motherhood is characterized by dramatic changes in brain and behavior, but less is known about fatherhood. Here we report that male sticklebacks-a small fish in which fathers provide care-experience dramatic changes in neurogenomic state as they become fathers. Some genes are unique to different stages of paternal care, some genes are shared across stages, and some genes are added to the previously acquired neurogenomic state. Comparative genomic analysis suggests that some of these neurogenomic dynamics resemble changes associated with pregnancy and reproduction in mammalian mothers. Moreover, gene regulatory analysis identifies transcription factors that are regulated in opposite directions in response to a territorial challenge versus during paternal care. Altogether these results show that some of the molecular mechanisms of parental care might be deeply conserved and might not be sex-specific, and suggest that tradeoffs between opposing social behaviors are managed at the gene regulatory level.

Parental care is critical for fitness, yet little is known about its genetic basis. Here, we estimate the heritability of parenting behaviour in a species famous for its diversity and its behavioural repertoire: three-spined stickleback ( Gasterosteus aculeatus ). Male three-spined stickleback are the sole providers of parental care that is necessary for offspring survival; therefore, this system offers the opportunity to study the inheritance of parental behaviour when selection is primarily acting on males. Fanning behaviour is a conspicuous parental behaviour that is readily quantified in this species. We show that the heritability of fanning behaviour is ≥0.9 and significantly different from zero within a freshwater population. Moreover, there was abundant genetic variation for fanning behaviour, indicating that it could readily evolve. These results suggest that parenting behaviour is tractable for further genetic dissection in this system., Competing Interests: We have no competing interests.

Background: Medical treatment in patients suffering from Parkinson's disease is very difficult as dose-finding is mainly based on selective and subjective impressions by the physician., Objectives: To allow for the objective evaluation of patients' symptoms required for optimal dosefinding, a telemonitoring system tracks the motion of patients in their surroundings. The system focuses on providing interoperability and usability in order to ensure high acceptance., Methods: Patients wear inertia sensors and perform standardized motor tasks. Data are recorded, processed and then presented to the physician in a 3D animated form. In addition, the same data is rated based on the UPDRS score. Interoperability is realized by developing the system in compliance with the recommendations of the Continua Health Alliance. Detailed requirements analysis and continuous collaboration with respective user groups help to achieve high usability., Results: A sensor platform was developed that is capable of measuring acceleration and angular rate of motions as well as the absolute orientation of the device itself through an included compass sensor. The system architecture was designed and required infrastructure, and essential parts of the communication between the system components were implemented following Continua guidelines. Moreover, preliminary data analysis based on three-dimensional acceleration and angular rate data could be established., Conclusion: A prototype system for the telemonitoring of Parkinson's disease patients was successfully developed. The developed sensor platform fully satisfies the needs of monitoring patients of Parkinson's disease and is comparable to other sensor platforms, although these sensor platforms have yet to be tested rigorously against each other. Suitable approaches to provide interoperability and usability were identified and realized and remain to be tested in the field.

Aims: The aim of the study was to evaluate the efficacy and clinical outcome of peritoneal dialysis (PD) treatment in patients with severe refractory heart failure (HF) and chronic kidney disease (CKD)., Methods and Results: The PD treatment was performed in 118 patients [49.2% New York Heart Association (NYHA) III and 50.8% NYHA IV] with a mean age of 73.2 ± 11.4 years as an in-centre-based and intermittent automated PD at least three times per week for 12 h per session and followed up for 1.11 ± 1.17 years. The functional status of those surviving for 6 months improved (P < 0.0001): 18 (32.1%) of all 60 patients with NYHA IV at baseline died within 6 months, 3 (5.4%) converted to NYHA III, 33 (58.9%) to NYHA II, and 2 (3.6%) to NYHA I. In all 58 patients with NYHA III at baseline, 14 (25.0%) died within 6 months, 27 (48.2%) converted to NYHA II, 12 (21.4%) to NYHA I, and 3 (5.4%) showed no improvement. In those surviving for 6 months, fluid overload was significantly reduced as body weight decreased, from 78.7 [95% confidence interval (CI) 75.8-81.7] to 74.7 (71.5-77.9) after 6 months after multiple imputation (P < 0.001). The overall survival rates after 3, 6, and 12 months were 77% (95% CI 70-85), 71% (95% CI 62-79), and 55% (95% CI 45-64). In the multivariate analyses, age, diabetes mellitus, serum urea, and brain natriuretic peptide were significantly associated with mortality. The incidence of peritonitis and catheter dysfunction was 0.053 (95% CI 0.014-0.093) and 0.084 (95% CI 0.034-0.133), respectively., Conclusion: The data suggest that PD is a safe, efficient, and well tolerated therapeutic tool for patients with refractory chronic HF and CKD.

Background: The impact of dialysis modality on outcome, especially on infection early in the course of dialysis, in unplanned acute dialysis initiation has not been well evaluated. The aim of the study was to compare the rates and causes of mortality and morbidity in incident dialysis patients started unplanned acute peritoneal dialysis (PD) or haemodialysis (HD)., Patients and Methods: In this observational cohort study, incident dialysis patients with initiation of unplanned and acute PD (n = 66) or HD (n = 57) at a single centre from March 2005 to June 2010 were included and followed up for 6 months (0-183 days, mean follow-up time 4.72 months). For PD, surgically placed Tenckhoff catheters were used. All HD patients were dialysed with a central venous catheter (non-tunnelled or tunnelled). There were no significant differences in terms of gender, age and prevalence of diabetes mellitus in either group. The prevalence of heart failure [New York Heart Association (NYHA) Stage III-IV] was significantly higher in the PD group (73 versus 46% in HD group, P < 0.01). The population was stratified to PD and HD comparing mortality, infection, bacteraemia and hospitalization., Results: Of the 123 patients who commenced acute and unplanned dialysis, n = 44 (35.8%) died during the follow-up period of 0-183 days. There were no significant difference in half-year mortality in n = 20 PD patients (30.3%) versus n = 24 HD patients (42.1%) (P = 0.19). The cardiovascular mortality in PD and HD patients were 9.1 and 10.5%, respectively (P = 1.00). Overall mortality due to infection was higher in the HD (17.5%) versus in the PD group (9.1%), however, not significant (P = 0.19). HD patients had significantly higher probability of bacteraemia in the first 183 days compared to PD patients (21.1 versus 3.0%, P < 0.01). Group comparison by Poisson regression analyses showed that the relative risk of bacteraemia in the PD group versus HD group was 0.16 (95% confidence interval, 0.05-0.57, P = 0.005). The significant difference was not affected by the confounder's patient age at time of dialysis, male sex, heart failure (NYHA III-IV), diabetes, malignancy and peripheral arterial occlusive disease Stage IV. There were high proportions of hospitalization after the initiation of dialysis in both groups (PD 75.0% and HD 67.3%, P = 0.40). Univariate and multiple regression analyses revealed only age at initiation of dialysis to be significantly associated with overall mortality (P < 0.05)., Conclusions: Dialysis modality (PD versus HD) in an acute unplanned dialysis setting showed, in our population, no significant influence on survival. HD patients had a significantly higher risk of bacteraemia, perhaps due to central venous dialysis catheter. PD seems to be a safe and efficient, at least comparable, alternative to HD in acute unplanned dialysis settings.

Aims: To estimate the impact of diabetes on the mortality of patients with incident renal replacement therapy (RRT)., Methods: We assessed the mortality of 544 incident RRT patients aged ≥ 30 years between 2002 and 2009 (57.9% men, mean age 70.3 years, 49.6% patients with diabetes) by analyzing the data of all dialysis centers covering a German region. We compared the estimated time-dependent hazard ratios of patients with and without diabetes by using the Cox proportional-hazards regression model., Results: Overall, 319 patients had died (158 diabetic), approximately 50% after 3 years. Up to about 3 years, the mortality rate was lower in diabetic than in nondiabetic patients. Thereafter, the survival curves crossed (interaction diabetes × time, p = 0.002; adjusted hazard ratios for diabetes: baseline, 0.66; year 1, 0.84; year 2, 1.05; year 3, 1.33; year 4, 1.68). The results were similar in men and women; however, the interaction of diabetes and time was significant only in men (p = 0.004). Further significant risk factors of mortality were age, sex, initial central venous catheter, cardiovascular disease, and malignancy., Conclusions: In this population-based study, the influence of diabetes was time-dependent, with a lower mortality in diabetic versus non-diabetic patients in the first three years but a higher mortality in these patients after 3 years. Results were similar in men and women., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: This study was conducted to estimate incidences of renal replacement therapy (RRT) in the diabetic and non-diabetic populations in Germany, as well as relative and attributable risks of RRT due to diabetes., Methods: Using the data of a regional dialysis centre (region population of 310 000), we assessed all incident RRT patients aged 30 years or older in 2002-08. We estimated sex- and age-specific and -standardized incidences of RRT in the diabetic and non-diabetic populations, which were estimated by applying diabetes prevalences from a population-based study, and relative and attributable risks due to diabetes., Results: Of all subjects with incident RRT (n = 544), 49.6% had diabetes. Fifty-eight percent were male, mean age (SD) was 70.3 years (11.4 years). Incidences per 100 000 person-years (standardized to the 2004 German population) in the diabetic and the non-diabetic populations were 213.7 [95% confidence interval (95% CI), 159.5-267.8] and 26.9 (95% CI, 22.5-31.3) in men and 130.2 (95% CI, 65.6-194.9) and 16.4 (95% CI, 13.5-19.3) in women, respectively. Standardized relative risks were 7.9 (5.9-10.8) in men and 8.0 (4.7-13.5) in women. There was a significant interaction between age and diabetes, with lower relative risks in higher ages. Attributable risks among diabetic individuals were 0.87 in men and women, and population-attributable risks were 0.41 and 0.35 in men and women, respectively., Conclusions: In this population-based study in a German region, we found the relative risk of RRT in the estimated adult diabetic population to be 8-fold increased compared with the non-diabetic population. A high proportion of the RRT risk can be attributed to diabetes in the diabetic as well as in the whole population.

Background: Population-based estimates of costs of renal replacement therapy are scarce in the literature. The aim of our study was to calculate the costs of long-term dialysis in 2006 on the basis of patient-specific data from a well-defined population in a region in western Germany (n = 310,757)., Methods: Cost estimation was performed from the perspective of the statutory health insurance. All dialysis patients from the study region (n = 344, 54% male, mean age (+/-SD) 69 +/- 13 years, 42% diabetic) were assessed for the costs of the dialysis procedures, dialysis-related hospital admissions, outpatient contacts outside of our dialysis center, dialysis-related medication, patient transportation and related costs (e.g. reimbursement fees on the basis of the German diagnosis-related group system, price scales). We estimated the cumulative cost per patient year in 2006 (in Euros), along with the 10th and 90th percentiles and the 95% confidence intervals (CI) by using bootstrapping procedures., Results: The mean total dialysis-related cost in 2006 was 54,777 Euros (95% CI, 51,445-65,705) per patient year. The largest part of the costs (55%) was caused by the dialysis procedures, followed by the costs of medication (22%), hospitalization (14%) and transportation (8%). The total cost increased significantly with increasing age. No significant association was found between total cost and sex, dialysis strategy, end-stage renal disease duration and diabetes., Conclusions: We present for the first time a cost estimation of dialysis in Germany on the basis of patient-level data in a population-based sample. Except age, patient characteristics were not significantly associated with costs. The largest part of the costs was caused by the dialysis procedures themselves; however, other dialysis-specific health care utilization also strongly contributed to the total cost.

Objective: Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores., Methods: Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months)., Results: There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores., Conclusion: In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

Aims: The B-type natriuretic peptide (BNP) has become increasingly important as a diagnostic and prognostic method for cardiovascular disease or death. To our knowledge no prospective studies exist to evaluate the value of baseline BNP and baseline heart failure as predictors of overall death in incident rather than prevalent hemodialysis patients with end-stage renal disease (ESRD)., Methods: 255 ESRD patients were included in our observational study with a median observation period of 1.11 years. A Kaplan-Meier survival curve was stratified by BNP concentration (< 340 pg/ml and > or = 340 pg/ml) to estimate the impact on the overall mortality rate. Univariate and multiple Cox regression models were fitted for a variety of covariables including severe heart failure (graded according to the New York Heart Association) to evaluate the independent predictors of death. Association between BNP and four explanatory variables was described in a multiple linear regression model., Results: Survival analysis demonstrated a significantly higher mortality rate in patients with higher BNP values at baseline. The independent predictive value of high BNP concentration at baseline could be statistically confirmed by multiple Cox regression analysis. However, when including the covariates hemoglobin and severe heart failure, significantly associated with BNP, in the same model, severe heart failure rather than BNP becomes a significant predictor of overall death., Conclusions: A higher BNP level at baseline may be confirmed as an independent predictor of death in the incident dialysis population. However, severe heart failure may affect the impact of BNP on the overall survival rate and thus be a stronger predictor of death than BNP.

A long-term female hemodialysis patient with end-stage renal disease due to Wegener's granulomatosis (WG) experienced a severe relapse when immunosuppressive therapy was switched from prednisone and cyclophosphamide to azathioprine maintenance therapy. Ten courses of protein A immunoadsorption therapy and switching immunosuppressive therapy to mycophenolate mofetil have proved to be very successful and free of side effects. The patient has fully recovered from all clinical WG symptoms and is still in remission ten months after the treatment.

Aims: To date, several different equations to predict the glomerular filtration rate (GFR) in patients with renal insufficiency have been developed for different patients groups. Our aim was to determine the prognostic factors of GFR in our homogenous patient group of obese, water-loaded patients with Type 2 diabetes and renal insufficiency, since we assumed that the endogenous creatinine clearance (ECC) alone may not be an accurate method to predict GFR., Method: We recruited 46 obese patients (37 men) with Type 2 diabetes and renal insufficiency in our nephrology center in Mettmann (Germany). However, two male patients were excluded from the analysis due to an outlying insulin level or low inulin clearance. The inulin clearance as a measure of renal function performed by the single shot method was compared with the GFR estimated by ECC, Cystatin C, and MDRD formula. Several multiple regression models were built to test the impact of the prognostic factors age, sex, body mass index (BMI), insulin resistance according to the homeostasis model assessment (HOMA), body water (TBW), brain natriuretic peptide (BNP), and proteinuria on the inulin clearance. In the main regression model to predict the inulin clearance by ECC, only the statistically significant prognostic factors of these models were selected, as well as the interaction between GFR predicted by ECC (GFR&#95;ECC) and BMI., Results: The prognostic factors GFR&#95;ECC, age, BMI, HOMA and proteinuria had a statistically significant impact on the inulin clearance (the gold standard of the GFR) in our patient population (p < 0.05). However, the interaction of GFR&#95;ECC and BMI was not significant (p = 0.06) in our model. The model was validated and considered well-fitted with a coefficient of determination (R2) of 0.69., Conclusions: The independent prognostic factors to determine GFR in obese, water-loaded diabetic patients are GFR&#95;ECC, age, BMI, HOMA and proteinuria. However, our model should be revalidated and tested in a larger sample size to probably detect an interaction between GFR&#95;ECC and BMI as an additional prognostic factor.

Aims: Infection is considered the second leading cause of death in dialysis patients with end-stage renal disease (ESRD). However, infection prevalence as primary cause of death still seems to be underreported in the literature. We investigated the role of C-reactive protein (CRP) levels shortly before death as predictor of dying from an infection as primary cause of death in this patient group., Method: Between January 1997 through March 2006, we defined the primary causes of death in 231 of the 481 incident patients in our single-center study, who died during this time and assessed the overall prevalence of infection at different predefined CRP cutpoints (between 2 and 300 mg/l). By means of an adjusted multiple logistic regression model, we calculated the odds ratio of (log) CRP for death in 346 survivors and non-survivors with available CRP levels within 5 days of death. In the 96 non-survivors (i.e. cases) of this group, the association of (log) CRP and causes of death was determined by the multiple linear regression model., Results: Infection as a primary cause of death was initially diagnosed in 42% of the 231 non-survivors by standard parameters and clinically. However, the rate of patients possibly dying from this disease increased accordingly when also including cases without any clinical infection signs but with CRP values higher than a given cutpoint (between 2 and 300 mg/l), e.g. when including all cases with CRP cutpoints higher than 100 mg/l, overall prevalence of infection as cause of death increases to 57% (95% CI = 51-64%). Infection was significantly associated with higher CRP levels compared with cardiac death (p < 0.001), with an odds ratio of log CRP for death of 5.4 (95% CI = 3.8-7.7)., Conclusions: Prevalence of infection as primary cause of death in ESRD patients may be even higher than currently stated in the literature. Therefore, to reduce mortality, infections should be further avoided and controlled in the future.

Background and Purpose: The appropriate medical approach to treat patients with end-stage renal disease (ESRD) and critical limb ischemia (CLI) is still controversial. The goal of this study was to investigate the survival rate of ESRD patients with foot ulcers who underwent femoropopliteal bypass surgery versus patients who did not receive any major surgical interventions., Patients and Methods: A 5-year Kaplan-Meier survival analysis of 99 ESRD subjects with foot ulcers, stage IV, recruited in the authors' single-center study between 1997 and 2005, was performed. 27 patients underwent bypass surgery because of meeting standard eligibility criteria for this procedure, and 72 patients received only conventional treatment due to their poorer vascular condition. Patients were censored upon major amputation during the observation period. Start of the observation was date of ulcer diagnosis., Results: Survival rate was 16.2% (standard error [SE], 0.08) in the bypass group versus 18.6% (SE, 0.06) in the non-bypass group (p = 0.92; log-rank test). Median time to bypass surgery was 0.36 years (range, 0-2.65 years) after ulcer diagnosis. Six patients of 27 (22.2%) were censored due to major amputation in the bypass group versus 25 patients of 72 (34.7%) in the non-bypass group., Conclusion: These results may suggest that bypass surgery in ESRD patients with foot ulcers as treatment of CLI is not the appropriate surgical approach, since this procedure does not seem to cause a better survival than in patients who could not undergo revascularization surgery because of their poorer overall vascular condition.

Background and Purpose: Diabetic subjects on hemodialysis have a poor survival. The authors performed a Kaplan-Meier survival analysis of diabetic versus nondiabetic subjects and investigated the value of diabetes as an independent predictor of death in these end-stage renal disease (ESRD) subjects., Patients and Methods: From 1997 to 2003, 135 ESRD subjects (41 diabetics) were enrolled in a survival study beginning at the start of dialysis. Inclusion criterion was onset of dialysis at least 6 months before study entry. Exclusion criteria comprised age < 45 years, coronary artery disease (CAD), critical limb ischemia (CLI), or malignancies at ESRD onset up to 6 months after study entry. Subjects with clinical signs of vascular disease were followed up by coronary or peripheral angiographies., Results: Baseline risk factors were similar between diabetic and nondiabetic subjects. The 5-year survival rate in nondiabetic subjects was 76.9% (95% confidence interval [CI] = 62-86%) versus 76.4% (95% CI = 53-89%) in diabetic patients (p = 0.402). Consistent with this finding, the Cox proportional hazards model revealed that diabetes does not significantly change the risk of death in ESRD subjects. De novo CAD developed in 35 and CLI in ten subjects, but both diseases were present more frequently in nonsurvivors (42% vs. 23%; p = 0.052) versus survivors (21% vs. 5%; p = 0.005)., Conclusion: Diabetes is not an independent predictor of death in the ESRD study group presented here. Prevention of CAD and CLI in diabetic subjects is most important to improve survival.

The article gives an overview on worldwide efforts to eliminate chemical weapons and facilities for their production in the context of the implementation of the 1997 Chemical Weapons Convention (CWC). It highlights the objectives of the Organisation for the Prohibition of Chemical Weapons (OPCW), the international agency set up in The Hague to implement the CWC, and provides an overview of the present status of implementation of the CWC requirements with respect to chemical weapons (CW) destruction under strict international verification. It addresses new requirements that result from an increased threat that terrorists might attempt to acquire or manufacture CW or related materials. The article provides an overview of risks associated with CW and their elimination, from storage or recovery to destruction. It differentiates between CW in stockpile and old/abandoned CW, and gives an overview on the factors and key processes that risk assessment, management, and communication need to address. This discussion is set in the overall context of the CWC that requires the completion of the destruction of all declared CW stockpiles by 2012 at the latest.

Fungal peritonitis (FP) and dialysate leakage have often been reported in association with continuous ambulatory peritoneal dialysis (CAPD), which has to be discontinued in many cases due to these complications. This report describes the first case of dialysate leakage into the urinary bladder of a 70-year-old male patient, after the area of the left ureteral ostium had been very deeply resected. The leakage probably led to severe fungal peritonitis developing 1 day after the ostium resection. The ostium resection was performed in November 2003 after detection of a carcinoma in situ (Cis) in this area and after previous bilateral nephroureterectomies due to multifocal urothelial carcinoma in the kidneys, ureters and bladder. In spite of prior fungal peritonitis and dialysate leakage, CAPD could be successfully initiated 41 days after biochemical manifestation of peritonitis and could be maintained in the patient because of the following reasons: early and effective treatment of FP with fluconazole and voriconazole, spontaneous occlusion of the slitted ostium area, allowance of enough healing time after 2 major abdominal surgeries, during which the patient was placed on extracorporal hemodialysis (which had been started 1 day after nephroureterectomy and ended after the antimycotic treatment) and thorough monitoring of the patient after starting CAPD. In January 2004, the patient could be placed on a cycler peritoneal dialysis and was fully rehabilitated 1 year later.

We describe the case of a 38-year-old woman with Guillain-Barré syndrome who was accidentally intoxicated with thimerosal, a column disinfectant containing ethyl mercury, during a protein A immunoadsorption treatment. The 1-time overdose caused by an equipment handling error led to a maximum blood serum mercury level of 2,250 microg/L, thus exceeding the normal blood reference range by a factor of approximately 200. Although the patient did not show short-or long-term clinical signs of mercury intoxication, she was treated with chelation therapy, and we replaced thimerosal with a commercially available mercury-free disinfectant, suggesting that thimerosal is no longer indicated for preservation of protein A columns.

Background: Patients with end-stage renal disease (ESRD) have a high overall mortality rate, particularly due to cardiovascular morbidity. In an era of decline in cardiovascular diseases and early cardiovascular intervention, non-cardiac diseases seem to have a larger impact on overall mortality., Methods: From 1997 to 2003, all incident haemodialysis patients in a single centre were enrolled in this prospective study. Those with clinical signs of vascular disease were examined by coronary or peripheral angiographies. Physicians took the patients' medical histories, examined them and followed them up until the end of the study or death. Causes of death were defined by the physicians., Results: In all, 322 patients were enrolled in the study, 38% of whom were diabetic. At the start of dialysis treatment, 38% had coronary artery disease (CAD), defined as >50% stenosis of at least one coronary artery or as definite myocardial infarction, and 14% had critical ischaemia of at least one limb (CLI). In all patients with foot lesions, CLI was defined angiographically, as evidenced by stenosis or rarefication of distal vessels in the legs. Patients who died (n = 121) [due to cardiac causes (n = 25), complications of CLI (n = 22), stroke (n = 10), cachexia following a long-standing, non-malignant disease (n = 6), malignancy (n = 24), infection not related to CLI (n = 18) and other causes (n = 16)] were older (71+/-10 vs 65+/-13 years), more often male [74/121 (61%)] and often diabetic [56/121 (46%)]. CAD was documented in 82/121 (68%). Five-year survivals in patients with no risk and diabetes without CAD or CLI, CAD and CLI were 74%, 73%, 50% and 10%, respectively. Age, CLI and smoking habits independently increased the risk of death (hazard ratios: 1.052, 4.921 and 2.292, respectively)., Conclusions: These results indicate that CLI with associated complications is not only an indicator of high mortality in patients with ESRD, but is also one of the main causes of death.

The development of the upper jaw during growth is influenced by the function and position of the tongue and perioral soft tissues, and the pressures exerted by them. Accurate determination of the forces exerted by the tongue would provide relevant information about this influence. To date, our ability to obtain continuous recordings of the tongue pressure during certain functions is limited. In this paper, an easy-to-employ and accurate telemetric system for such functional measurements is presented. The system, consisting of four piezoresistive pressure sensors, a microcontroller, a telemetric module and batteries, is integrated within a removable orthodontic plate and transmits the measured data out of the oral cavity to a receiver.

We described a pressure sensor probe suitable for assessing dynamic rectal pressure profiles. It comprises 10 piezoresistive sensors mounted in low-temperature co-fired ceramic. To protect against corrosion, the sensors are coated with a biocompatible silicone elastomer. The ceramic measures 4.5 x 5.5 x 1.4 mm. The entire probe has a diameter of 9 mm and a length of 20 cm. A healthy test subject was submitted to rectal manometry. The experimental data and analysis of linearity, hysteresis errors, temperature dependence and reproducibility are discussed. The sensor probe extends classical anorectal manometry, in particular with regard to the diagnosis of rectal motility disorders.

Guards on machine tools are meant to protect operators from injuries caused by tools, workpieces, and fragments hurled out of the machine's working zone. This article presents the impact resistance requirements, which guards according to European safety standards for machine tools must satisfy. Based upon these standards the impact resistance of different guard materials was determined using cylindrical steel projectiles. Polycarbonate proves to be a suitable material for vision panels because of its high energy absorption capacity. The impact resistance of 8-mm thick polycarbonate is roughly equal to that of a 3-mm thick steel sheet Fe P01. The limited ageing stability, however, makes it necessary to protect polycarbonate against cooling lubricants by means of additional panes on both sides.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus simultaneously on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain. This part examines pharmacologic methods.

Low back pain is a leading cause of work-related disability and has important socioeconomic consequences. Although there is little evidence to determine the optimal treatment of chronic low back pain, treatment goals can be established. Primary care providers should focus on pain management, improvement of activity and functional level, and fostering a greater understanding of chronic low back pain. This two-part article summarizes consensus guidelines developed by practitioners with expertise in pain management, family medicine, internal medicine, physical therapy, rheumatology, and managed care, and provides direction for primary care providers on a multidisciplinary approach to the patient with chronic low back pain.

This 6-week, multicenter, double-masked, placebo-controlled study compared the efficacy, tolerability, and safety of the recommended starting dose of oxaprozin (1200 mg/d) and a 1500-mg/d dose of nabumetone in the treatment of patients with moderate-to-severe osteoarthritis (OA) of the knee. A total of 347 patients with a mean age of 61.1 years were randomized to receive oxaprozin (116 patients), nabumetone (115 patients), or placebo (116 patients). Adults of either sex who were older than 18 years of age were eligible for entry into the study, if they had had OA of the knee for at least 6 months. Efficacy variables included knee pain on weight bearing, knee pain on motion, patients' and physicians' global assessments of OA, pain intensity as measured on a visual analog scale, and time to walk 50 feet as quickly as possible. Efficacy variables were assessed at baseline and at weeks 1, 2, 4, and 6. Between-group differences in efficacy variables were evident by week 1. Mean improvements were significantly greater with oxaprozin than with placebo for all efficacy variables at all time periods, except knee pain on motion at weeks 2 and 4 and time to walk 50 feet at weeks 1, 2, and 4. Mean improvements were significantly greater with nabumetone than with placebo for all efficacy variables at all time periods, except the following: knee pain on weight bearing at weeks 2, 4 and 6; knee pain on motion at weeks 2 and 4; patients' global assessment at week 4; and pain intensity as measured on a visual analog scale at weeks 2 and 4. There were, however, no significant differences between oxaprozin and nabumetone in any of these efficacy variables. Adverse events were reported by 83 (71.6%) patients who took oxaprozin, by 80 (69.6%) patients who took nabumetone, and by 57 (49.1%) patients who took placebo. Adverse events were reported for significantly more patients taking oxaprozin or nabumetone than placebo. However, adverse events tended to be mild or moderate and rarely resulted in patients withdrawing from the study. Combined with the results of an earlier study, the results of this study showed that a 1500-mg/d dose of nabumetone, which is higher than the recommended starting dose of 1000 mg/d, is required for efficacy equivalent to that of the recommended starting dose of oxaprozin, 1200 mg/d, in relieving the symptoms of OA. Thus nabumetone may require dosage titration from the recommended starting dose. Oxaprozin and nabumetone were found to have similar tolerability profiles, as shown by adverse-event monitoring and withdrawal rates, as well as clinically similar safety profiles, as demonstrated by physical examinations, hematologic and biochemical laboratory testing, hemoccult testing, and adverse-event monitoring and symptom assessment.

In minimal invasive surgery high sensory palpation of the organs is largely lost. It is the purpose of this work to recover tactile sensing for the surgeon. To achieve this goal, a new tactile optical pressure sensor has been developed which allows to display 64 measuring points on a 0.64 cm2 surface area with a digital resolution of 12 bits. The sensor has been conceived for application in laparoscopic grasping forceps and can also be integrated into a sensing rod, both 15 mm in outside diameter. This optical sensor allows us to display graphically indurations spread in the tissue. Furthermore, the measured values serve to activate a vibrotactile display unit for tactile feedback onto the surgeon's fingertip. In order to obtain further information about the requirements for an analog tactile display, an actuatorarray with 144 pins on a 4 cm2 surface area was built. The array allows various test objects to be recognized in a true scale presentation by exploratory movements of the fingers.

This multicenter, 6-week, double-blind, placebo-controlled, parallel-group study compared the efficacy and safety of oxaprozin 1200 mg once daily with that of nabumetone 1000 mg once daily in patients with moderate-to-severe osteoarthritis (OA) of the knee. To be eligible, patients had to experience a flare of OA within 2 weeks of discontinuing their usual OA medication (nonsteroidal anti-inflammatory drug or analgesic). Eligible patients were assessed at baseline and then randomized to receive oxaprozin (n = 109), nabumetone (n = 110), or placebo (n = 109). Efficacy assessments were performed at weeks 1, 2, 4, and 6. Primary efficacy variables included knee pain on weight bearing, knee pain on motion, and patient's and physician's global assessments of OA. Secondary efficacy variables included pain intensity, time to walk 50 feet, and duration of morning stiffness. Safety was evaluated by use of routine laboratory analyses; physical examination at screening, baseline, and week 6 (or study termination); assessment of symptoms at baseline and at each visit; and testing stools for occult blood at screening and between week 4 and the final visit. Adverse events were monitored throughout the study. Between-group differences in efficacy variables were evident by week 1. The mean change in improvement from baseline with oxaprozin compared with placebo was statistically significant in favor of oxaprozin at weeks 1, 2, 4, and 6 for all primary efficacy variables. The mean change in improvement from baseline with nabumetone compared with placebo, however, was statistically significant only at week 1 for knee pain on motion, patient's global assessment, and physician's global assessment. The mean change in improvement from baseline was statistically significant (P < or = 0.035) in favor of oxaprozin versus nabumetone at weeks 2 and 6 for all four primary efficacy variables and also at week 4 for knee pain on motion. The incidence of adverse clinical events between treatment groups was not statistically significant. However, nine oxaprozin-treated patients had asymptomatic liver enzyme elevations reported as adverse events. Four of these patients had reversible elevations of aspartate aminotransferase and alanine aminotransferase greater than three times the upper limit of normal range (P < 0.05); two of these patients were taking other medications known to induce liver enzyme abnormalities. The study showed that oxaprozin 1200 mg once daily was statistically significantly more efficacious than nabumetone 1000 mg once daily for the treatment of patients with moderate-to-severe OA of the knee. Both drugs were clinically well tolerated.

Precise cutting combined with reliable coagulation of the margins of the lesion is an important requirement for dissection techniques in endoscopic surgery. These requirements are met by the two most common ancillary energy sources applied for endoscopic dissection today, electrosurgery and "thermal lasers", mostly the Nd:YAG. For the comparison of the histological effects of monopolar and bipolar high frequency with the Nd:YAG laser an experimental in vitro and in vivo study has been performed. In order to evaluate the advantages of non thermal dissection for endoscopic procedures, a water jet cutting system was included in the in vitro study. In parenchymatous tissue the water jet was found to be the least traumatic technique, followed by bipolar high frequency, laser and monopolar high frequency. The water jet was not applicable for intestinal dissection since uncontrolled bloating of the rectal wall with uncontrolled disruption of the tissue layers occurred. A general disadvantage is that secure haemostasis in the line of incision is hard to achieve. In the microscopic comparison of the shape of the incision, the Nd:YAG laser produced the smoothest lesions with well-defined margins. The monopolar technique was more often associated with irregular and sometimes fissured margins. These results were confirmed in the in vivo part of the study (Transanal Endoscopic Microsurgery).

The article discusses handling problems in endoscopic surgery and concepts for the augmentation of instrument dexterity. The authors present a kinematic concept for improved surgical tool positioning and orientation. Using a trunk mechanism it is possible to assure augmented dexterity and stiffness for endoscopic handling. The paper addresses the use of steerable endoscopic instruments in a manipulator system for minimal invasive surgery.

The augmenting complexity of minimal invasive interventions requests a continuous improvement of technologies. Extended endoscopic procedures, e.g. laparoscopic-transanal sigmoidectomy or thoracoscopic esophagus dissection require difficult surgical manipulations like mobilisation, sceletonization as well as ligatures and sutures. They are difficult to perform with the present endo-surgical instruments. A major instrumental weakness is represented by the restricted steerability because of the rigid shaft axis and the resulting low degrees of freedom (DOF). Therefore a series of steerable flexible instruments has been developed in interdisciplinary cooperation between surgeons and engineers. The prototypes provide a multi-joint working as the instrument's elbow, which allows to incline the tip around +/- 280 degrees. The second additional DOF is the rotation of the surgical tool. The prototypes have been experimentally tested in laparoscopy and thoracoscopy, showing a clear improvement in the carrying out of complex operative manipulations. The further development is performed in modular conception, including electric drives.

A prospective study of 45 consecutive patients (27 men, 18 women, mean age 42 [22-64] years) who had undergone allogeneic renal transplantation was carried out to ascertain whether rejection of the graft can be detected by routine follow up with colour-coded Doppler ultrasonography even in the presence of acute renal failure requiring dialysis. Conventional diagnostic methods detected 44 episodes of rejection in 33 patients: 26 of these arose in 18 patients with acute renal failure requiring dialysis and 18 in 15 patients who did not require dialysis. Colour-coded Doppler ultrasonography was used to determine the "pulsatility index" (PI) at intervals of 3 to 6 days. 17 of the 18 episodes of rejection occurring in transplant patients with stable serum creatinine levels (3.41 +/- 1.48 mg/dl) were detected by colour-coded Doppler ultrasonography 3.8 +/- 5.6 days earlier than by conventional diagnostic methods, the indicator being the rise in PI (sensitivity 93.8%). 25 of the 26 rejection reactions which arose in patients with oligo-anuria due to post-operative renal failure were detected 2.0 +/- 2.7 days earlier (sensitivity 96%). The rise in PI was greater in episodes of vascular rejection than in purely interstitial rejection episodes (40.9 +/- 73.9% versus 10.0 +/- 8.8% per day). Colour-coded Doppler ultrasonography ia a new, highly sensitive, noninvasive method for the early detection of rejection reactions after renal transplantation. Acute postischaemic renal failure does not reduce its sensitivity.

In plasma, 40% of the protein S is free and functions as a cofactor for the anticoagulant effects of activated protein C. The remaining 60% of protein S is complexed to C4b-binding protein and is functionally inactive. A family with hereditary C4b binding protein deficiency has been identified with C4b-binding protein levels in an affected father and daughter of 37 micrograms/mL and 23 micrograms/mL, respectively; these values are significantly below the normal range for this protein of 180 micrograms/mL +/- 44 micrograms/mL (mean +/- 2 SD). The total protein S (free + bound) is normal in these individuals (23.2 micrograms/mL and 17.8 micrograms/mL, respectively; normal 19.1 micrograms/mL +/- 6.0 micrograms/mL). The free protein S levels are markedly increased at 22.5 micrograms/mL and 17.4 micrograms/mL, respectively (normal 5.9 micrograms/mL +/- 2.4 micrograms/mL). This experiment of nature shows that total protein S levels in plasma are not affected by the absence of C4b-binding protein and that chronic elevation of free protein S is not associated with increased hemorrhagic tendencies.

The nailfold capillary pattern of 48 Type I diabetic patients with longstanding disease and of 15 normal controls was studied using the technique of widefield nailfold capillaroscopy. Twenty-six diabetic patients had documented vascular disease (retinopathy) and 27 had flexion contractures of the hand. No distinctive morphologic capillary lesions were observed in any diabetic patient, nor were any differences in capillary loop number or density found between the diabetic and control groups. While vascular disease is a prominent feature of diabetes, it is not reflected in the appearance of the nailfold capillary pattern.

Primary deficiency of the C4 binding protein (C4bp) was present in a patient with disease clinically resembling Behçet's disease. Her father and her sister were also deficient. This protein, as a cofactor for factor I, interferes with the assembly of, and accelerates the decay of, the classical C3 convertase. Thus, the deficiency favours C3 conversion by classical pathway activation. In addition to genital and oral ulceration, cutaneous vasculitis and synovitis, our patient had relapses complicated by angioedema, atypical for Behçet's disease. It is not clear whether her total disease, or only the complicating angioedema, was a consequence of the C4bp deficiency.

Results of clinical, serologic and histologic studies documenting an association between hereditary C6 deficiency and a connective tissue disease are provided. The propositus had systemic lupus erythematosus with prominent discoid features, Sjögren's syndrome and hyperthyroidism. Serum C6 was undetectable by radial immunodiffusion and hemolytic assays. Serologic and typing studies performed on 9 family members suggested an autosomal codominant transmission. No correlation with a specific HLA phenotype was established.

The 6-phosphofructo-1-kinase (PFK) subunits and isoenzymes were studied in human muscle, heart, brain, liver, platelets, fibroblasts, erythrocytes, placenta and umbilical cord. In each tissue, the subunit types in the native isoenzymes were characterized by immunological titration with subunit-specific antibodies and by column chromatography on QAE (quaternary aminoethyl)-Sephadex. Further, the subunits of the partially purified native isoenzymes were resolved by SDS/polyacrylamide-gel electrophoresis, identified by immunoblotting, and quantified by scanning gel densitometry of silver-stained gels and immunoblots. Depending on the type of tissue, one to three subunits were detected. The Mr values of the L, M and C subunits regardless of tissue were 76,700 +/- 1400, 82,500 +/- 1640 and 86,500 +/- 1620. Of the tissues studied, only the muscle PFK isoenzymes exhibited one subunit, which was the M-type subunit. Of the other tissues studied, the PFK isoenzymes contained various amounts of all three subunits. Considering the properties of the native PFK isoenzymes, it is clear that, in human tissues, they are not simply various combinations of two or three homotetrameric isoenzymes, but complex mixtures of homotetramers and heterotetramers. The kinetic/regulatory properties of the various isoenzyme pools were found to be dependent on subunit composition.

This report summarizes the course of a patient with asymptomatic chronic pancreatitis associated with hemorrhage into the pancreatic duct and metastatic fat necrosis. Retrograde cannulation of the pancreatic duct and superior mesenteric arteriography established the presence of a pseudocyst with a pancreatic duct-arteriovenous (DAV) fistula as the cause of the syndrome. Ligation of feeder vessels with external drainage of the cyst as the initial surgical procedure stopped the bleeding but failed to prevent recurrence of the pancreatic duct-venous fistula. A pancreaticoduodenectomy with resection of the cyst and fistula was required to arrest destruction of distant tissues. Although serum and urine amylase concentrations were markedly elevated, serum lipase levels were normal throughout the patient's course. Elevation of serum lipase does not seem to be a necessary condition for the development of the metastatic fat necrosis syndrome.

The SER allows the "deformability" of individual red blood cells to be quantitated by determining their passage time through a pore (d = 5.8 microns, 1 = 50 microns) under the shear stresses of 1.5 Pa-4 Pa. Using this system, we examined the influence of: 1. cytoplasmic viscosity, 2. membrane viscoelastic properties, 3. area to volume relationship. To change these determinants of RBC-deformability, the cells have been altered with 1. Acetylphenylhydrazine (0.016 mol/l), 2. diamide (0.5 mmol/l), 3. osmotic swelling (200 mosm/l) and osmotic shrinking (480 mosm/l) by suspending the cells in hypo- and hypertonic saline. The passage time has been found to be primarily influenced by changes in cytoplasmic viscosity. The same cells when tested in 4 other systems considered to measure RBC-deformability (filtrometer, packed cell viscometry, rheoscope and ektacytometry) behaved differently.