[Risk of Stroke After Exacerbation of Ischemic Heart Disease: Data of 3­Years Follow-up].

PURPOSE: to analyze possible associations of clinical and genetic factors with development of ischemic stroke after exacerbation of ischemic heart disease (IHD). MATERIALS AND METHODS: The Russian multicenter study aimed at assessment of risk of unfavorable outcomes after exacerbation of IHD "Exacerbation of IHD: logical probabilistic ways to course prognostication for optimization of treatment" (meaning of Cyrillic acronym - oracle) was conducted in 16 centers of 7 cities in Russia. We included into the study 1 208 patients with unstable angina and ST-elevation or non-ST-elevation myocardial infarction (MI). Data on outcomes were known for 1 193 patients, 15 patients were lost for follow-up. RESULTS: Mean duration of follow-up was 644±14.45 (4-1 995) days. Shortest, longest, and mean time before development of stroke was 22, 1433 and 389±56.6 days after inclusion. Patients with strokes were older, more often had history of IHD prior to index hospitalization, arterial blood pressure level compatible with stage 3 arterial hypertension, less often were smokers, and more often had MI recurrences or repetitive episodes of severe ischemia during the index hospitalization. Patients also more often had documented atrial fibrillation during hospitalization, and lower level of glomerular filtration rate. Of studied genetic markers carriage of A allele of polymorphic marker G (-1082) A of interleukin-10 gene was significantly associated with risk of stroke development. Using linear regression analysis, we constructed a model of estimation of the stroke development risk. Comparison of diagnostic value of different scales for stroke risk assessment showed that area under the curve was 0.656, 0.686, and 0.756 for the GRACE, CHA2DS2­VASc, and ORACLE scores, respectively.

Inhibition of prostate cancer growth by estramustine and colchicine.

Hormone-refractory prostate cancer continues to be associated with a very poor prognosis. Agents that inhibit microtubule function have been found to be cytotoxic to prostate cancer cells in preclinical and clinical settings. It was the aim of this study to assess the activity of estramustine and colchicine, two microtubule inhibitors, in hormone-refractory prostate cancer. In clinically achievable concentrations, the combination of estramustine and colchicine was cytotoxic to both the Dunning rat prostate adenocarcinoma cell line MAT-LyLu (MLL) and human prostate cancer cells (PC-3). Microtubule function was assessed in vitro to evaluate possible mechanisms of action. In motility and cell cycle analysis assays, estramustine and colchicine inhibited cellular motility but not cell cycle transit. In vivo, these two agents both inhibited the growth of implanted Dunning rat prostate adenocarcinoma MLL cells but did not appear to have additive effects. The use of oral colchicine in the treatment of hormone-refractory prostate cancer requires further investigation.

Preclinical studies of gossypol in prostate carcinoma.

Hormone refractory prostate cancer remains an incurable disease and the discovery of newer agents with higher cytotoxic activity is required. Gossypol is a phenolic compound isolated from cottonseed oil which has been shown to have anti-spermatogenic effects. In in vitro studies, gossypol appears to inhibit the growth of rat prostate cancer cell line MAT-LyLu and human prostate adenocarcinoma cell lines PC-3, LNCaP and DU-145. In vive, gossypol appeared to inhibit tumor growth of subcutaneously implanted MAT-LyLu cells in Copenhagen rats. Gossypol may be an active agent for the treatment of hormone refractory metastatic prostate cancer.

An evaluation of lateral and medial transposition of the ovaries out of radiation fields.

BACKGROUND: Transposition of the ovaries is practiced in young women before possible radiation to the pelvic fields. In patients with carcinoma of the uterine cervix (Ca cervix), the ovaries are transposed laterally (LOT), whereas in patients with Hodgkin's disease (HD), they are usually transposed medially (MOT). Nevertheless, not all transposed ovaries are successfully protected. METHODS: Computed tomography was performed in 16 patients (7 Ca cervix and 9 HD) after ovarian transposition. The location of all identified ovaries was depicted on diagrams of the respective radiation fields for evaluation of the efficacy of LOT or MOT in relocating the ovaries out of these fields. RESULTS: All 13 ovaries transposed laterally were easily identified by CT, as compared with only 13 of 18 ovaries transposed medially (P = 0.2). Eleven of the 13 ovaries that underwent lateral transposition (6 of 7 patients) were located outside the radiation field. In contrast, only 3 of 13 identified ovaries in the medially transposed group were completely outside the radiation field (P = 0.005). Of the remainder, six were completely within the radiation field, and four were at least partially within the radiation field. CONCLUSIONS: Although LOT achieves its purpose in patients with Ca cervix, the use of MOT in patients with HD should be revised to achieve better protection of the ovaries from the effects of radiation. The authors suggest that LOT is preferred over MOT also in patients with HD if radiation of the pelvic lymph nodes is planned.

Cytotoxic chemotherapy for advanced renal cell carcinoma.

This article reviews 72 cytotoxic chemotherapeutic agents used singly or in a limited number of two drug combinations. Results in 3502 adequately treated patients show objective response (complete and partial remissions) in only 197 or 5.6% (95% CI, 4.8% to 6.4%). Although some data suggest that a few drugs need further evaluation, at this time, renal cell carcinoma must be considered a chemotherapeutically resistant cancer.

Cytotoxic chemotherapy for advanced hormone-resistant prostate cancer.

BACKGROUND: Advanced adenocarcinoma of the prostate after hormonal manipulation has been noted to be a relatively chemotherapeutic nonresponsive tumor. Earlier reviews have reported objective responses, that is, complete and partial remissions in 6.5% of 3184 patients, and the current review examines the efficacy of new agents. METHODS: The current review consists of 26 new drug trials culled from papers and abstracts published between 1987-1991. RESULTS: Results of these 26 drug trials found a similar trend, 8.7% (95% confidence interval, 6.4-9.0%), indicating that hormone-resistant adenocarcinoma of the prostate still fails to respond to most cytotoxic agents. The most interesting of the new therapeutic agents is the combination of vinblastine plus estramustine. Only six agents had an objective response rate greater than 10%, such as vinblastine by continuous infusion, trimetrexate, mitoguazone, and estramustine. The recent introduction of radioactive-labeled monoclonal antibodies is intriguing and these will undoubtably be used as carriers for radiotherapeutic and cytotoxic compounds. CONCLUSIONS: Although multidrug resistance may explain the marginal efficacy of cytotoxic drugs, methods to overcome such resistance and, more importantly, new classes of agents must be developed. In addition, reliable disease markers must be found for osseous and visceral metastases to avoid the prevailing confusion in evaluating more precisely the destruction of prostate cancer cells.

Idiopathic preretinal macular gliosis: a retrospective study of 200 patients.

The charts of the last 200 patients with idiopathic preretinal macular gliosis (IPRMG) seen in the Retina Service of Montefiore Medical Center, Albert Einstein College of Medicine, were reviewed. We found that IPRMG is a disease of older people, tends to have a nonprogressive course, and rarely causes severe visual loss. In our series, 91.5% of the patients were older than 50 years of age, 80% of eyes lost less than two lines of vision, and only 4% of eyes had a visual acuity 20/200.

Synthesis of eicosanoids by circulating mononuclears in healthy people and in patients with liver cirrhosis.

The synthesis of some of the products of cycloxygenase and lipoxygenase metabolism of arachidonic acid (AA) in mononuclear cells (MNCs) in vitro was studied with [3H]AA in five healthy subjects and five patients with liver cirrhosis (LC). FGA, ionophor Ca A23187 and levamisole were investigated. The eicosanoid synthesis by non-stimulated MNCs of the patients was normal. Mitogens augmented the outcome of PGs, TXB2 and HETE and increased the outcome of LTB4 in comparison with the control group. In liver pathology prostanoid and LT synthesis differed. In patients, but not in healthy subjects, prednisone suppressed eicosanoid production stimulated by FGA and reduced LTB4 and HETE outcome in MNCs treated by ionophor. The role of LTB4 hyperproduction in the pathogenesis of LC and the possibility of prednisone-induced suppression of synthesis of lipoxygenase metabolites in MNCs are discussed.

Prognostic factors for survival of patients with advanced urothelial tumors treated with methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy.

Between February 1983 and February 1986, 132 patients with advanced urothelial tract tumors were treated with methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin (M-VAC) chemotherapy. Analysis of prognostic factors for survival of the first 92 patients was undertaken using the Cox proportional hazards model. Normal alkaline phosphatase and high Karnofsky performance status (KPS) were predominant for long survival. Patients 60 years or older at initiation of therapy were likely to survive longer than younger patients, perhaps indicating physician selectivity of older patients for this therapy, and those with initial hemoglobin in the normal range were also likely to survive longer. The additional 40 patients' data were used to validate the model. Clinical implications of the prognostic factors are discussed.

Experimental studies of chemosensitivity testing of urothelial cancer grown in nude mice.

The present study provides information relevant to a number of variables which may influence response to treatment of nude mouse-grown human urothelial cancer. A number of xenotransplanted tumors were exposed to selected treatments at different transplant generations, and at various dose levels and treatment schedules. It was observed that nude mouse-grown tumors were characterized by consistency, reproducibility and biological stability not affected by the transplant generation at which they were examined. Treatment related dose response curves were steep, the sharpness of the curves depending on the degree of tumor sensitivity. Best therapeutic results were obtained at the maximum tolerated dose of cytotoxic agents under study and of importance, a 20% to 40% dose reduction with the same treatment schedule resulted in little or no activity. In addition, treatment schedule, timing and sequence of treatments and to a certain degree, tumor grade were important variables which could influence tumor response. The nude mouse-human tumor system provides important preclinical guidelines on dose, schedule, sequence and timing of treatments and can assist in designing more efficient clinical trials.

Overview of systemic treatment of bladder cancer and results with M-VAC therapy.

Cytotoxic chemotherapy is playing an increasingly important role for advanced disease, and is being properly evaluated in prospective trials as neoadjuvant therapy. There has been no major undertaking to examine adjuvant treatment, and hopefully randomized studies will be started in the future. There is sparse data concerning the effectiveness of immunological agents for treatment of this tumor, and phase II efficacy studies are needed. Future studies will need to define more accurately the poor-risk group in whom new agents or regimens using a more intensive schedule, perhaps with G-CSF, can be explored as initial therapy.

Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse.

Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M-VAC regimen), significant tumor regression occurred in 72% +/- 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% +/- 9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2-year and 3-year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse at the time of progression. Three patients with non-TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T less than pathologic [P] restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 N3-4M0 patients who achieved CR versus 33% of 100 with N0-+M+ lesions. Toxicity was significant with 4 (3%) drug-related deaths, 25% incidence of nadir sepsis, 58% greater than or equal to 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens.

Schedule dependency of the combination methotrexate-vinblastine against human urothelial cancer grown in nude mice.

The combination of methotrexate (MTX) and vinblastine (VLB) was evaluated using different doses and treatment schedules in human transitional cell carcinoma line SW-1738, TCC-K1 and TR-49 grown in the nude mouse. Maximally tolerated weekly doses of MTX, 30 mg/kg, and VLB, 3 mg/kg, were given intraperitoneally for four consecutive weeks singly, concurrently, and separated by 24, 48 and 72 hour intervals. MTX-VLB drug sequence was not a factor in determining tumor regression or response rates when the second agent was administered 24 or 48 hours after the first agent. However, when VLB was administered 72 hours after MTX, a significant statistical difference (0.005 greater than p greater than 0.001) was observed for all tumor lines studied compared to either controls, simultaneous administration of both agents and/or VLB administered 24 or 48 hours after MTX. Additionally, dose reduction of either agent by 30% proved ineffective. Thus, tumor response to MTX-VLB combination was dependent both on schedule and dose. Application of this schedule dependency may be beneficial in management of urothelial tract tumors.