Renal gluconate excretion after 6-aminonicotinamide

Summary After application of 6-aminonicotinamide, an increasing amount of gluconate was found in the urine. No correlation with the renal excretion of electrolytes could be established.     

The Dartmouth COOP Charts: A simple,reliable, valid and responsive quality of life tool for chronic obstructive pulmonary disease

The negative impact of chronic obstructive pulmonary disease (COPD) on health-related quality of life (HRQL) is substantial. Measurement of HRQL is increasingly advocated in clinical practice; traditional outcome measures such as lung function are poorly responsive. However many HRQL tools are not user-friendly in the clinic setting. Hence HRQL is often neglected. The Dartmouth Cooperative Functional Assessment Charts (COOP) have the requisite attributes of a tool suitable for routine clinical practice: they are simple, reliable, quick and easy to perform and score and well accepted. We aimed to determine the reliability, validity and responsiveness of the COOP in patients with significant COPD. HRQL was assessed during a prospective, randomised, placebo-controlled, double-blind, 12 week cross-over interventional study of ambulatory oxygen in patients (n = 50) with COPD. Test–retest reliability of the COOP domains was only modest however it was measured over a 2 month period. Significant correlations ranging between 0.4 and 0.8 were observed between all comparable domains of the COOP and the Medical Outcomes Study 36-item Short-form Health Survey, Chronic Respiratory Questionnaire (CRQ) and Hospital Anxiety and Depression (HAD) scale. Following ambulatory oxygen significant improvements were noted in all CRQ and HAD domains. Several domains of the generic SF-36 (role emotional, social functioning, role-physical) showed significant improvements. Comparable domains of the COOP (social activities, feelings) also showed significant improvements. The COOP change in health domain improved very significantly. The COOP is a simple, reliable HRQL tool which proved valid and responsive in our study population of COPD patients and may have a valuable role in routine clinical practice.     

Serum antibodies against the hepatitis C virus E2 protein mediate antibody-dependent cellular cytotoxicity (ADCC)

BACKGROUND/AIMS: The role of antibody dependent cellular cytotoxicity (ADCC) in HCV infection is unclear at present. Antibodies mediating ADCC are usually directed against viral envelope proteins. As cell surface expression of the HCV envelope E2 protein has been shown, the HCV E2 protein is an especially promising candidate target for ADCC. METHODS: Sera from patients with acute (n=6), self-limited (n=11) and chronic (n=19) HCV infection were analyzed in this study. Sera reacting with cell-bound HCV antigens were examined in a flowcytometric cytotoxicity assay using antigen-coated JOK-1 cells as targets. RESULTS: We found that sera from all stages of HCV infection reacted with cells loaded with HCV E2. E2-specific ADCC was observed in patients with acute (n=3/6), self-limited (n=5/11) and chronic (n=13/19) hepatitis C and was closely related to fluorescence intensity in the E2-binding assay (r=0.67, P<0.001). CONCLUSIONS: We conclude that E2-antibodies from all stages of HCV infection can mediate ADCC. Thus, the role of this process in the pathogenesis of chronic hepatitis C should be further elucidated.     

Implant dentistry at the focus of liability lawsuits

PURPOSE: In recent years, the growing readiness on the part of dental patients to take legal action has resulted in an increasing number of medical liability lawsuits. The aim of this retrospective analysis was to highlight aspects of these lawsuits of special significance, to subject them to both qualitative and quantitative analysis, and to show how conflicts can be avoided. MATERIALS AND METHODS: Forty relevant court decisions from the year 1984 onwards were found in online databases and through direct inquiries at the courts. These were supplemented by 21 reports prepared by experts at the University of Muenster, Department of Dental Medicine, commissioned by courts in connection with ongoing lawsuits. Analysis was initially based on formal aspects of the cases and reports. It was later supplemented by differentiated assignment of the questions addressed by the courts to the expert consultants. The principles underlying the judgments as to the liability arising from the terms of the contract were also assigned to the expert consultants in a differentiated manner. RESULTS: The results revealed marked differences in the frequency of liability-prone aspects of treatment. While the majority of judgments referred to the obligation to take due care during the preparatory and treatment phases, infringement of the obligations to provide information and to keep records played more than a minor role. Moreover, 90% of all cases represented combined charges covering various aspects, including those related to consequential failings. DISCUSSION AND CONCLUSION: The detailed qualitative analysis of the grounds quoted and of the lines of reasoning can therefore be summed up in clearly defined recommendations aimed at helping the clinician avoid conflicts by observing the judicial requirements.     

Proteinase 3 sidesteps caspases and cleaves p21(Waf1/Cip1/Sdi1) to induce endothelial cell apoptosis

BACKGROUND: Emerging data raise possibilities of a complex and specific biologic role for leukocyte-derived proteases in substrate processing and in signaling pathways. Neutrophil proteinase 3 (PR3) is a caspase-like protease that enters endothelial cells, cleaves nuclear factor-kappaB (NF-kappaB), and induces sustained JNK activation, implying that the major cell cycle inhibitor p21 may be inactivated. Cleavage of p21 by caspase-3 is reported to be required for endothelial cell apoptosis. We hypothesized that PR3 may target p21. METHODS: Human umbilical vein endothelial cells (HUVEC) were treated with or without PR3 (5 microg/mL) from 0 hours or up to 8 hours, and analyzed for changes in cell cycle control proteins by immunoblotting, immunofluorescence and flow cytometry. RESULTS: PR3 exposure resulted in cleavage of p21 between Thr80 and Gly81, loss of nuclear p21 by cytoplasmic sequestration and depletion of p21 from cyclin/cyclin-dependent kinase (CDK) complexes. Examination of cyclins D and E, p53, Rb, and p27 revealed a largely nonproliferative expression profile. Cells arrested in G1 were more susceptible to PR3 effects. We examined inflamed human colonic tissue and found a fragment similar in size to that generated by PR3 in HUVEC. Granzyme B, a T-cell homologue of PR3 that cleaves caspase substrates, also cleaves p21 between Asp62 and Phe63. A reported substrate of granzyme B and caspases, Bid, is cleaved by PR3 signifying commonality of substrates among these proteases. CONCLUSION: A theme is developing that the granulocyte protease, PR3, is an exogenous caspase-like molecule that can sidestep intracellular caspase functions at sites of inflammation.     

Influence of orthopaedic-technical aid on the kinematics and kinetics of the knee joint of patients with neuro-orthopaedic diseases

In our gait laboratory, the gait pattern of 18 youths with neurogenic foot deformities as a result of spina bifida or cerebral palsy was examined. The influence of technical orthopaedic devices for the foot and ankle on kinematics and kinetics of the gait and especially of the knee joint were analyzed. Kinematic data were derived from 3D-video analysis, kinetic data from force plates and pressure distribution plates. Muscle activities were measured with eight-channel EMG. The data were examined to see if there were differences when using the technical devices. All patients had already been supported externally with the different devices like orthopaedic shoes, insoles, Nancy Hilton orthoses and orthoses for the lower leg extremity. The devices restricted to the foot and the ankle joint improved the feeling of gait stability of the patients. In this investigation, the different supports had various but little effects on the kinematics and kinetics of the knee joint, depending on the type of orthoses used and the kind of handicap of the youths. Because of the great expenditure, the data obtained in this study were taken from a small number of patients. Therefore, they are individual findings and are of restricted general significance.