Survival of patients with advanced urothelial cancer treated with cisplatin-based chemotherapy

The aim of the present retrospective study was to assess long-term survival after cisplatin-based chemotherapy in 398 patients with advanced urothelial transitional cell carcinoma (TCC) treated at seven international oncological units. Various combinations of cisplatin, methotrexate, vinblastine (or vincristine) and doxorubicin were used. The complete response rate according to the WHO criteria was 17%. Partial responses were obtained in 42% of the patients. The overall cancer-related 2 year and 5 year survival rates were 21% and 11% respectively. Based on multivariate analyses, a good prognosis group could be identified comprising patients with a good performance status with disease confined to lymph nodes (14%) or patients with T4b disease only. These patients had a 28% 5 year survival rate, which, in part, has to be related to post-chemotherapy consolidation treatment in patients with pelvis-confined disease (radiotherapy, 26%; total cystectomy, 11%). Fifteen patients died of chemotherapy-related complications and in 16% of the patients toxicity led to discontinuation of treatment. Modern cisplatin-based chemotherapy leads to long-term survival and cure of selected patients with advanced urothelial transitional cancer. In routine clinical practice, chemotherapy should be offered to good prognosis patients; those presenting with a good performance status and a non-metastasising T4b tumour or with metastases confined to lymph nodes. Post-chemotherapy consolidation treatment by surgery or radiotherapy should always be considered. Such chemotherapy requires oncological expertise in order to avoid unnecessary toxicity.     

Acute myelomonocytic leukemia preceded by secondary amenorrhea and presenting with central diabetes insipidus: a case report

The antigenic components of Fasciola gigantica somatic extract were revealed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting technique using sera from patients with F. gigantica infection, patients with clinically diagnosed fascioliasis, patients with other infections/illness and healthy adults. By SDS-PAGE, it was found that the somatic product comprised more than 22 polypeptides. Immunoblotting analysis revealed at least 13 components which were strongly recognized by sera of patients with fascioliasis. These antigenic components had molecular weights ranging from less than 14.4 to more than 94 kDa. One antigenic component, i.e. 38 kDa was found to give a consistent reaction with sera of patients with fascioliasis (100% sensitivity and 96.7% specificity). The finding suggests that the 38 kDa components may be a potential diagnostic antigen for fascioliasis.     

Married couples' experiences at a human reproduction center

The present study was intended to understand the feeling demonstrated by married couples seeking a Human Reproduction Center for infertility evaluation. Intending to understand the way Assisted Reproduction is experienced from the couple's perspective, a phenomenological approach was adopted and the directing question was: "How do you feel using the Assisted Reproduction as a treatment?"     

Mutation of PTB binding sites causes misregulation of alternative 3' splice site selection in vivo

Alternative splicing of pre-mRNA is a commonly used mechanism to regulate gene expression in higher eukaryotes. However, with the exception of regulated cascades in Drosophila, the cis-acting elements and the trans-acting factors that control tissue- and/or developmentally regulated splicing remain largely unidentified. Cis-acting elements that control smooth muscle-specific repression of exon 3 of alpha-tropomyosin (alpha-TM) have been identified recently and consist of two regions that flank this exon. Deletion of either element causes misregulated splicing of alpha-TM in transfected smooth muscle cells. In experiments designed to characterize essential sequences within each element and the factors that interact with these sequences, we have identified two overlapping sequences within the downstream regulatory element (DRE) that are identical to binding sites for polypyrimidine tract binding protein (PTB) that were identified using iterative selection techniques. Mutation of these sites caused aberrant splicing regulation in transfected smooth muscle cells. In addition, sequences identical to high-affinity PTB binding sites were also detected upstream of exon 3 and mutation of these sites also resulted in misregulation of splicing in vivo, suggesting that PTB binding to specific sequences flanking exon 3 is responsible, in part, for the repression of exon 3. Consistent with this hypothesis, UV crosslinking and equilibrium binding assays confirm that the same mutations that cause misregulated splicing also disrupt PTB binding to RNA.     

Morphological observations on motor end-plates in rabbits with experimental myasthenia

The morphology of motor end-plates in rabbits immunized with Torpedo nicotinic acetylcholine receptor (nAChR) has been studied by light and electron microscopy. Rabbits were studied either after one period of paralysis, some in parallel with electrophysiological recordings of MEPPs and EPPs and of Naja naja alpha-neurotoxin binding properties or after recovery followed by a second paralysis. Changes in the sub-neural apparatus were noted after cholinesterase staining only in the latter group. Ultrastructurally, however, most end-plates in both groups contained a wide range of abnormalities. Many were similar in appearance to those observed in human myasthenia gravis (MG). This further supports the theory that immunized rabbits can be used as a model for myasthenia gravis. In the rabbits with 1 period of paralysis an acute stage of influence on the neuromuscular junction seemed to be present while simplified motor end-plates typical for human MG were mostly found in rabbits with 2 periods of paralysis. Short post-synaptic folds in conjugation with thickeneed membrane-bound vesicles at their tops, inside the basement membrane, were frequently observed. These were interpreted as if the crests of the folds containing nAChR had degenerated and had been budded off. If so, a large number of receptor sites had been lost which would be one possible explanation for the lowered capacity of the muscles to bind Naja naja alpha-neurotoxin. Membrane thickenings with projections and striations were interpreted as reflecting ACh receptors and were observed in the post-junctional membrane without proximity to the nerve terminal. The degeneration of the top of the post-synaptic folds and the occurrence of receptors at other locations within the motor end-plate will result in a widened distance between the nerve terminal and the receptors, which can explain previous interpretations of a presynaptic defect in MG.     

Spine deformity index in osteoporotic women: relations to forearm and vertebral bone mineral measurements and to iliac crest ash density

Bone densitometric measurements are widely used for monitoring therapeutic regimens for osteoporosis. However, it is a matter of debate which measurement site is most appropriate for prediction of individual fracture risk. The aim of this cross-sectional study was to investigate the relationship between bone mineral measurements at various sites and spine deformity index (SDI) in osteoporotic women. The SDI was determined in 37 osteoporotic women aged 56-87 years (mean 70.9 years). Peripheral (single-photon absorptiometry of the distal forearm, and iliac crest ash content) and axial (dual-photon absorptiometry of the lumbar spine) bone mass measurements were obtained. SDI increased with age (r = 0.34, p < 0.05), whereas forearm BMC (r = -0.52, p < 0.002) and forearm BMD (r = -0.62, p < 0.0001) decreased. No significant age-related changes were observed in lumbar BMC or iliac crest ash content in these osteoporotic women. A highly significant correlation was found between SDI and lumbar BMC (r = -0.60, p < 0.01). A significant, but less pronounced correlation was found between SDI and forearm BMC (r = -0.37, p < 0.05), whereas no relation was revealed between SDI and forearm BMD or iliac crest ash content. In a multiple regression model, the relationship between lumbar BMC and SDI remained significant after adjusting for the influence of age, whereas the relationship to forearm BMC disappeared. Furthermore, a multiple regression analysis was performed in order to evaluate the ability of all four bone mass measurements and age to predict variations in SDI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer

PURPOSE: To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients. PATIENTS AND METHODS: Thirty-five chemotherapy-naive patients with suboptimally debulked stage III (tumor masses > 3 cm) and stage IV ovarian cancer were entered onto this phase I trial in which paclitaxel was administered as a 3-hour intravenous (IV) infusion at dosages of 125 to 225 mg/m2 immediately followed by carboplatin over 30 minutes at dosages of 300 to 600 mg/m2. A total of six courses was planned, followed by a second-look laparoscopy/laparotomy. Patients with a response and/or minimal residual disease at second-look laparoscopy received three additional courses. Twenty-six patients participated in the pharmacokinetic part of the study. RESULTS: The most important hematologic toxicity encountered was neutropenia. Neutropenia was more pronounced for the higher dose levels (DLs) and was cumulative. Thrombocytopenia was mild in the first eight DLs, but increased during the treatment courses. Nonhematologic toxicities consisted mainly of vomiting, neuropathy, fatigue, rash, pruritus, myalgia, and arthralgia. Dose-limiting toxicities (DLTs) in this trial were neutropenic fever, thrombocytopenia that required platelet transfusions, and cumulative neuropathy. Of 33 patients assessable for response, 26 major responders (78%, 20 complete response [CR] and six partial response [PR]) were documented. The maximal concentration (Cmax) of paclitaxel and the area under the concentration-time curve (AUC) were not different from the historical data for paclitaxel as a single agent. Retrospective analysis using a modified Calvert formula showed that the measured carboplatin AUCs in plasma ultrafiltrate (pUF) were 30% +/- 3.4% less than the calculated carboplatin AUC. Neutropenia was more pronounced than could be expected on the basis of the historical times above a threshold concentration greater than 0.1 mumol/L (T > or = 0.1 mumol/L) or 0.05 mumol/L (T > or = 0.05 mumol/L), and thrombocytopenia was less than could be expected from historical sigmoidal Emax models. CONCLUSION: The combination of paclitaxel 200 mg/ m2 and carboplatin 550 mg/m2 every 4 weeks is a well-tolerated treatment modality. The paclitaxel-carboplatin combination is highly active in stage III (bulky) and stage IV ovarian cancer. No indications for a pharmacokinetic drug-drug interaction between carboplatin and paclitaxel were found.     

Use of a general surgical high dependency unit in a district general hospital: the first 10 years

The chemotherapy regimen of paclitaxel and carboplatin produces an objective response in 30%-60% of patients with non-small-cell lung cancer (NSCLC). In a prospective study, we administered paclitaxel 200 mg/m2 (by 1-3-hr infusion) and carboplatin at an area under the plasma concentration curve (AUC) of 5 (by the Calvert formula) every 3 weeks to 21 patients who had previously received predominantly platinum-based chemotherapy for NSCLC. We observed no objective responses. Patients received a median of 2 cycles before disease progression. Three of 5 patients who had received only single-agent treatment with a relatively inactive agent may have had modest clinical benefit. We conclude that the paclitaxel/carboplatin regimen has minimal activity in previously treated patients with NSCLC.