Relationship between schistosomiasis and bladder cancer

Carcinoma of the urinary bladder is the most common malignancy in the Middle East and parts of Africa where schistosomiasis is a widespread problem. Much evidence supports the association between schistosomiasis and bladder cancer: this includes the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer, and extensive evidence in experimentally infected animals. Multiple factors have been suggested as causative agents in schistosome-associated bladder carcinogenesis. Of these, N-nitroso compounds appear to be of particular importance since they were found at high levels in the urine of patients with schistosomiasis-associated bladder cancer. Various strains of bacteria that can mediate nitrosation reactions leading to the formation of N-nitrosamines have been identified in the urine of subjects with schistosomiasis at higher intensities of infection than in normal subjects. In experimental schistosomiasis, the activities of carcinogen-metabolizing enzymes are increased soon after infection but are reduced again during the later chronic stages of the disease. Not only could this prolong the period of exposure to activated N-nitrosamines, but also inflammatory cells, stimulated as a result of the infection, may induce the endogenous synthesis of N-nitrosamines as well as generating oxygen radicals. Higher than normal levels of host cell DNA damage are therefore anticipated, and they have indeed been observed in the case of alkylation damage, together with an inefficiency in the capacity of relevant enzymes to repair this damaged DNA. In experimental schistosomiasis, it was also found that endogenous levels of host cell DNA damage were related to the intensity of infection. All of these factors could contribute to an increased risk of bladder cancer in patients with schistosomiasis, and in particular, the gene changes observed may have potential for use as biomarkers in the early detection of bladder cancer that may assist in alleviating the problem.     

Relevance of systemic lupus erythematosus nephritis animal models to human disease

Systemic lupus erythematosus (SLE) is characterized by spontaneous B and T cell autoreactivity and multiorgan immune injury including severe glomerulonephritis. This autoimmune syndrome results from a global derangement in immune regulation dependent on the interaction of complex genetic and environmental susceptibility factors. Animal models have provided a powerful tool to study disease mechanisms and novel therapeutic interventions under well-defined conditions, and bypass the barriers inherent in the study of human lupus. Classical models of spontaneous and investigator-induced murine lupus, their mutant variants, and novel transgenic and gene-targeted mutant lineages have been particularly useful. Extensive genome typing in inbred and recombinant lupus-prone strains permits mapping and characterization of multiple lupus susceptibility loci and genes and their contribution to various disease phenotypes. Murine models provide important insight into the identity of targeted self-antigens, the molecules and pathways that maintain tolerance, immune cell and cytokine interactions that promote autoimmunity, and mechanisms of renal localization and injury by immune effectors. These models reveal that multiple and independent mechanisms contribute to disease pathogenesis and provide a better understanding of the remarkable phenotypic and histopathologic heterogeneity that characterizes human SLE.     

4-Defect repair of grade 4 cystocele

PURPOSE: The 4-defect repair of grade 4 cystocele corrects discrete and severe deficiencies of vesicourethral support. We describe this technique used during pelvic reconstruction in 130 women. MATERIALS AND METHODS: During a 3-year period 130 patients (age range 35 to 96 years) underwent repair of grade 4 cystocele using the 4-defect repair technique. Cystocele repair had been performed in 60 patients (46%) and hysterectomy had been performed in 85 (65%). A "goalpost incision" is used in the vaginal wall to facilitate separation of the wall from underlying perivesical fascia, entry into the retropubic space, and exposure of the urethropelvic ligament, cardinal ligament and perivesical fascia. The 4 polypropylene sutures are used to provide an anterior vaginal wall sling which is modified to incorporate perivesical fascia and cardinal ligaments. Central defect repair is achieved by approximation of the cardinal ligaments and midline plication of the perivesical fascia over absorbable mesh. RESULTS: A total of 112 patients were available for followup which ranged from 6 to 42 months (mean 21). Repair of grade 4 cystocele was accompanied by other transvaginal repairs in 94 patients (83%), including rectocele repair in 81, hysterectomy in 22 and enterocele repair in 31. Of the patients 92% had excellent objective and subjective results for anatomical cystocele repair. Of the patients with preoperative stress urinary incontinence 90% had excellent or good subjective results. De novo urge incontinence was seen in 7% of patients. CONCLUSIONS: The 4-defect repair technique relies on anatomical restoration of 4 distinct deficiencies of pelvic support and is highly effective for relief of symptoms of grade 4 cystocele.     

Epicondylopathia humeri. The indication for, technic and clinical results of radiotherapy

BACKGROUND: The efficacy of radiotherapy for degenerative-inflammatory disorders is well known, but so far long-term observations and reliable assessment of symptoms according to objective criteria and scores for validation are still missing. PATIENTS AND METHOD: From 1986 to 1991, 104 patients with refractory epicondylopathia humeri were irradiated. 85 patients or 93 elbows (due to double-sided symptoms) were documented in long-term follow-up according to objective criteria. All patients had received intensive therapy. Pain symptoms were quantified in "categories" and "grades" prior to and 6 weeks after radiotherapy and at last follow-up. In addition, the elbow score of Morrey et al. [36] was used for long-term evaluation. The onset of pain symptoms was acute in 41 and chronic in 52 cases. The mean symptom duration prior to radiotherapy was 16 months. Pain was mostly triggered off during professional (46) or sportive activities (23) or spontaneously (11). Fifty-one patients were severely disabled in professional or sportive activities. The involved elbow(s) received 2 radiotherapy series of 6 x 1 Gy (total 12 Gy) with 3 fractions per week; the second radiotherapy series was started 6 weeks after the first series. Mean follow-up was 4 +/- 2 (1 to 8) years. RESULTS: Forty-three patients (50 elbows) achieved "complete pain relief (CR)" in all pain categories: 59% elbows with pain at strain had "complete pain relief", 79% with pain at night, 84% with permanent pain, 80% with pain at rest and 81% with pain at initiation or morning stiffness. Nineteen elbows gained "major pain relief (PR)", i.e. had minor symptoms (maximum grade 1) in all categories. Thus, a total of 69 (74%) elbows responded to radiotherapy. Seventeen patients (19 elbows) were operated because of persistent symptoms or dissatisfaction in long-term follow-up; 7 of those became completely free of symptoms. The Morrey-Score improved by a mean of 18 points from 78 prior to radiotherapy to 96 points at last follow-up. According to the Morrey-Score only 2 patients became worse in long-term follow-up. Two parameters indicated a negative prognosis in multivariate analysis: long symptom duration prior to radiotherapy and immobilisation with plaster (p < 0.05). CONCLUSIONS: Radiotherapy for refractory epicondylopathia humeri is highly effective. Long symptom duration and long-term immobilisation by plaster are negative prognostic factors for treatment outcome. Due to the low side effects and treatment costs, radiotherapy is a good therapeutic option in comparison to conventional treatment methods and surgery in the chronic stage of epicondylopathia humeri.     

Desensitizing GABAC receptors on carp retinal bipolar cells

Bicuculline- and baclofen-insensitive GABA receptors (GABAC receptors) on bipolar cells acutely dissociated from carp retina were investigated with using the whole-cell patch-clamp recording technique. The currents of these cells mediated by GABAC receptors showed striking desensitization, even at low concentrations of GABA. Both the time constant tau of the GABAC current decay and the extent of desensitization were significantly different from that of GABAC receptors previously observed in other retinas and elsewhere in the CNS, suggesting that the GABAC receptors of carp bipolar cells might be distinct in intracellular mechanisms and subunit composition.