Incorrectly sited PEEP valve.
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Biomedical subjects
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AIMS: To investigate whether prognosis in micropapillary urothelial carcinoma is related to the proportion of the micropapillary component (MPC), and to identify the immunohistochemical features of MPC. METHODS AND RESULTS: This study presents a clinicopathological analysis of 20 patients with micropapillary urothelial carcinoma of the bladder with cystectomy specimens for evaluation. Tumours were stratified on the extent of MPC: focal, <10%; moderate, 10-50%; extensive, >50%; and this was correlated with tumour stage and prognosis. Sixteen males and four females were aged 56-81 years (mean 69 years). All cases had high-grade morphology in the micropapillary carcinoma and typical urothelial carcinoma. All cases with extensive MPC (n = 4) were of a high pathological stage (pT3 or pT4) and died of disease (DOD) or other causes. Eighty percent with moderate MPC (eight of 10 cases) were pT3 or pT4 and 50% DOD or are alive with disease. Eighty-four percent with focal MPC (five of six cases) were pT1 or pTa. In high-stage cases, the most invasive component was MPC. High-stage cases had an 85% risk of being advanced at presentation with micropapillary carcinoma. All pT2 or lower stage cases had micropapillary carcinoma on prior transurethral resections of bladder tumour (TURB). High-stage carcinomas had 30% and 54%, respectively, of surface MPC and urothelial carcinoma in situ, in comparison with 85% and 28% in lower stage carcinomas. Immunohistochemical staining was similarly positive in MPC and typical urothelial carcinoma with cytokeratin (CK)7, CK20, epithelial membrane antigen, carcinoembryonic antigen and cytokeratin 34betaE12. CA125 staining was seen only in MPC in 43% of cases. CONCLUSIONS: Micropapillary urothelial carcinoma is a high-grade carcinoma in which the prognosis is related to the proportion and location of the MPC. Cases with moderate or extensive MPC are at high risk of being advanced at presentation. Cases with <10% MPC and surface MPC have a high chance of detection at an early stage. The morphology and immunohistochemical profile of the MPC suggest that it is a form of glandular differentiation in urothelial carcinoma.
UNLABELLED: BACKGROUND/PATIENTS AND METHODS: Thirty-two patients with recurrent head and neck cancer (HNC) following radiotherapy and/or surgery were treated with eniluracil (10 mg/m2) and 5-fluorouracil (5-FU) (1 mg/m2) (E5F) orally twice daily for 28 days followed by a seven-day treatment free period. Thirty-five-day cycles were repeated until disease progression, unacceptable toxicity or patient refusal. Doses were modified for toxicity. Standard toxicity and response criteria were used. RESULTS: Thirty-two patients were accrued; thirty-two and twenty-eight patients were evaluable for toxicity and response, respectively. Twelve patients received three or more cycles of E5F. Drug related toxicities were usually grade 1-2 intensity and included lethargy, nausea or diarrhea (> or = 25% of patients), and anorexia, rash or itch, stomatitis or vomiting (12%-24% of patients). Hematologic toxicity was generally mild; two patients experienced grade 3-5 leukopenia or thrombocytopenia. No significant biochemical toxicity was seen. One patient was withdrawn (severe nausea and vomiting) and one patient died because of drug related toxicity (thrombocytopenia). In the final analysis there were one complete and four partial responses for a 15.6% overall response. CONCLUSIONS: E5F demonstrates activity in chemotherapy naïve patients with advanced HNC cancer with acceptable toxicity profile. Further investigation of E5F with other active agents is warranted in HNC.
PURPOSE: Bone scanning is the most common diagnostic imaging service requested by Australian rheumatologists, who order $50,000 (Australian) worth of bone scans annually. METHODS: To determine why rheumatologists request bone scans and how they affect their patient management, the authors administered a two-part prospective survey before and after every bone scan ordered by four rheumatologists during a 6-month period in 1996. RESULTS: A total of 136 bone scans were requested. The primary indications for scanning were to confirm a clinical diagnosis (38%), to exclude a diagnosis (34%), and to localize the site of pain (17%). The common diseases that rheumatologists were attempting to confirm or exclude with bone scanning were inflammatory arthritis, malignancy, and fracture. However, the most common provisional and final diagnosis was soft tissue rheumatism (18%), followed by inflammatory arthritis (15%) and osteoarthritis (11%). Bone scans were successful in excluding a diagnosis in 87% and confirming a diagnosis in 80%. In 32%, bone scans altered the clinical diagnosis, and in 43% they changed the course of disease management. Bone scan results prevented further investigations in 60%.
PURPOSE: This multicenter phase II trial investigated the efficacy and toxicity of a combination of the novel intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), and doxorubicin in patients with anthracycline-naïve metastatic breast cancer. Preclinical models and early single institutional studies suggested DPPE could potentiate the cytotoxicity of doxorubicin. PATIENTS AND METHODS: Forty-two women, 32 to 77 years old (median, 59 years), with anthracycline-naïve metastatic breast cancer were treated. Patients may have had one previous regimen of nonanthracycline chemotherapy, either in the adjuvant or metastatic disease treatment setting. DPPE (6 mg/kg) was administered as an 80 minute intravenous infusion with doxorubicin (60 mg/m(2)) given intravenously over the last 20 minutes of the DPPE infusion. Patients were premedicated with an antiemetic and sedating regimen. The DPPE/doxorubicin treatment was given every 21 days for a maximum of seven cycles. RESULTS: All 42 patients were assessable. Overall, toxicity was comparable to that expected with doxorubicin alone, with the exception of DPPE-related motion sickness, mild hallucinations, and cerebellar signs at the time of the infusion. These CNS side effects were manageable in an ambulatory care setting, improved with subsequent cycles of treatment, and did not usually require hospitalization. Four patients developed febrile neutropenia. Thirty-five patients received four or more cycles of chemotherapy. The overall response rate was 52.5% (95% confidence interval, 36% to 68%), with 9.5% complete responses (n = 4), 43% partial responses (n = 18), and 38% of patients with stable disease (n = 16). CONCLUSION: The antitumour effects of DPPE/doxorubicin the 52.5% response rate seems encouraging, particularly in consideration of the fact that a recently reported randomized National Cancer Institute of Canada Clinical Trials Group trial using single-agent doxorubicin 60 mg/m(2) in one of the treatment arms achieved a 31% response rate. Thus, a randomized phase III trial of doxorubicin versus doxorubicin plus DPPE is being conducted in this clinical setting.
Recently, we identified a novel putative nuclear receptor in colonic crypt cells distinct from both mineralocorticoid receptor and glucocorticoid receptor, with high affinity for 11-dehydrocorticosterone (11-DHB) (33). In the present study, competitive nuclear binding assays demonstrated that this site has a unique steroid binding specificity that distinguishes it from other steroid receptors. Western blot analysis showed the presence of 11beta-hydroxysteroid dehydrogenase-2 (11betaHSD2) but not 11betaHSD1 in colonic crypt cells and showed that 11betaHSD2 was present in the nuclear pellet. Differences in steroid specificity between the putative DHB receptor and inhibition of 11betaHSD activity indicate that binding is not to the enzyme. Furthermore, modified Chinese hamster ovary cells transfected with the 11betaHSD2 gene express nuclear 11betaHSD2 but not a nuclear DHB binding site. In conclusion, these data support the existence of a novel nuclear DHB receptor in rat colon that is distinct from the classic steroid receptors and from both 11betaHSD1 and 11betaHSD2.
BACKGROUND: Drug treatments for multiple sclerosis are expensive, may cause side effects, and do not have demonstrated efficacy for cognitive deficits associated with this disease. OBJECTIVE: To test the effectiveness of a multimodal cognitive therapy on cognitive and physical measures known to be affected in multiple sclerosis. DESIGN: Quasi-experimental wait-list control. SETTING: Alternative medicine clinic. PATIENTS: 27 persons with clinically definite multiple sclerosis. INTERVENTION: Multimodal cognitive therapy. MAIN OUTCOME MEASURES: Neuropsychological measures of verbal learning and memory, abstraction, vocabulary, and information processing speed; Beck Depression Inventory; tactile sensitivity of the hands; grip strength; and visual acuity. MAIN RESULTS: 12 of 14 patients in the therapy group and 10 of 13 patients in the control group completed 24 weeks of treatment and all assessments. Patients who received therapy showed significantly greater improvement in verbal learning, verbal abstraction, depression, and some measures of grip strength and tactile sensitivity than did patients in the untreated control group. The groups did not differ in the magnitude of change on vocabulary, information processing speed, or visual acuity. CONCLUSION: Cognitive therapy appears to be a promising treatment for ameliorating some symptoms of multiple sclerosis. A larger study with a randomized design and additional outcome measures is warranted.
Mice that are immune-suppressed by thymectomy and by sequential treatment with 1-beta-D-arabinofuranosylcytosine and whole body irradiation may be used as hosts for generation of human tumor xenografts. We have studied the effect of various additional methods of immune suppression on the formation of tumors after i.m. injection and on the formation of lung colonies after i.v. injection with the human MGH-U1 bladder cancer cell line. Success of transplantation was improved by treatment of immune-suppressed animals with either heterologous antilymphocyte serum or a monoclonal anti-Thy-1.2 antibody. Success of lung colony formation was also improved by antilymphocyte serum but not by monoclonal anti-Thy-1.2 antibody. Admixture of heavily irradiated cells (10(6)) to the viable inoculum of tumor cells in addition to antilymphocyte serum treatment improved the success of i.m. transplantation but not that of lung colony formation. Treatment with corticosteroids or treatment with carrageenan to suppress macrophage activity added toxicity and did not improve the success of xenografting. Immune suppression decreased the natural killer cell activity of normal mice and treatment with antiinterferon to further suppress natural killer cells may also enhance xenograft formation. Administration of cyclosporin A to normal mice allowed the growth of a single xenograft but was not a useful method for immunosuppression. The success of xenografting into immune-deprived mice was superior to that for two strains of nude mice maintained in our laboratory, and i.v. injection of tumor cells did not lead to lung colonies in these nude mice. Immune-deprived mice are a useful alternative to nude mice for the study of xenografts derived from human tumor cell lines and may allow the study of experimental lung metastases.
Fibroblast cell lines obtained from five patients with the early onset form of Tay Sachs disease (TSD) possess a species of beta-N-acetylhexosaminidase (Hex) which is more anionic than Hex B but which is stable to heating under conditions which completely inactivate Hex A. This species, which comprised between 3 and 20% of the total hexosaminidase activity in homozygous TSD fibroblasts, appeared to be unstable and upon isoelectric focussing produced a mixture of Hex B (pI = 7.2) and an isozyme with a pI of 6.2. This intermediate form of hexosaminidase was not seen in two normal fibroblast cell lines but was observed following anion exchange chromatography of extracts of fibroblast cell lines obtained from two obligate heterozygotes. A species of hexosaminidase with the same chromatographic properties, thermostability and isoelectric point as the intermediate form found in fibroblasts with the TSD genotypes can be recovered after anion exchange chromatography of a partially purified preparation of human liver Hex A that had been treated with merthiolate. We hypothesize that in TSD cells a form of the beta subunit which is usually incorporated into Hex A accumulates due to the absence of alpha subunits. This form of the beta subunit is more anionic than the beta subunit found in Hex B. In the absence of alpha subunits these anionic beta subunits form tetramers with a pI = 6.2. This form of the enzyme is unstable in the presence of cellular proteases and may be modified to Hexosaminidase B.