The systemic involvement in scleroderma

A survey was made of the systemic involvement in 38 patients with scleroderma: 33 with the acrosclerotic form (Type 1, 18, Type 2, 15) and five with the diffuse form. The study comprised inquiry about symptoms, physical examination, and the laboratory tests, such as radiological examination of chest and hands, barium swallow and meal X-ray examination, electrocardiography, pulmonary function tests, haematology tests, examination for autoantibodies, and a battery of biochemical tests. Evidence of some systemic involvement (that is, in addition to skin) was almost universal. Similar disturbances occurred both in the acrosclerotic and in diffuse forms. The most common clinical involvement was that of the joints and gastrointestinal tract. The most common confirmatory signs were a positive "neck test" (tethering of the skin of the root of the neck and upper part of the chest on extending the head) and telangiectasia. The most common abnormalities in test results were those found in X-ray films of the hands (about 80%), and in pulmonary function, and barium swallow and meal X-ray studies (each about 70%). The most frequent abnormalities in the biochemical scan were increased levels of immunoglobulin M (IgM), and decreased creatine clearance.     

Methods to improve diagnostic accuracy in a community mental health setting

OBJECTIVE: This study determined the extent to which adding structured procedures improved diagnostic accuracy for outpatients with severe mental illness in a community mental health setting. METHOD: The Structured Clinical Interview for DSM-III-R (SCID) was used to interview 200 psychiatric outpatients. A research nurse reviewed medical records and amended the SCID diagnoses accordingly. A research psychiatrist or psychologist reviewed the diagnostic data and interviewed each patient to verify or further modify the previous findings. Diagnostic outcomes at each step of the procedure were compared to determine whether adding additional data improved diagnostic accuracy. The additional time required for each element of the diagnostic procedure was also assessed. RESULTS: Kappa comparisons of the different diagnostic levels showed that adding additional data significantly improved accuracy. Diagnoses rendered by combining the SCID and review of the medical record were the most accurate, followed by the SCID alone, and then diagnoses made by psychiatrists during routine care. In addition, the SCID alone identified five times as many current and past secondary diagnoses as were documented routinely in patients' charts. CONCLUSIONS: Combining structured interviewing with a review of the medical record appears to produce more accurate primary diagnoses and to identify more secondary diagnoses than routine clinical methods. The patients' knowledge of their diagnoses was limited, suggesting a need for patient education in this setting. Whether use of structured interviewing in routine practice improves patient outcomes deserves further study.     

Chronic ophthalmoplegia with anti-GQ1b antibody

Anti-GQ1b antibodies are typically found in patients with the Miller Fisher syndrome, all of whom will have, by definition, acute ophthalmoplegia. The authors describe three patients with chronic ophthalmoplegia in the presence of persistently high titers of immunoglobulin G anti-GQ1b antibody detected in an ELISA, one of whom improved with immunotherapy. Anti-GQ1b antibodies may be associated with some cases of chronic ophthalmoplegia of unknown cause.     

Angiographically defined collateral circulation and risk of stroke in patients with severe carotid artery stenosis. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group

BACKGROUND AND PURPOSE: Blood supply through collateral pathways improves regional cerebral blood flow and may protect against ischemic events. The effect of collaterals on the risk of stroke and transient ischemic attack (TIA), in the presence of angiographic severe internal carotid artery (ICA) stenosis, was assessed. METHODS: Angiographic collateral filling through anterior communicating and posterior communicating arteries and retrograde filling through ophthalmic arteries were determined in all patients at entry into the North American Symptomatic Carotid Endarterectomy Trial. Kaplan-Meier event-free survival analyses were performed on 339 medically treated and 342 surgically treated patients. RESULTS: The presence of collaterals supplying the symptomatic ICA increased with severity of stenosis. Two-year risk of hemispheric stroke in medically treated patients with severe ICA stenosis was reduced in the presence of collaterals: 27.8% to 11.3% (P=0.005). Similar reductions were observed for hemispheric TIA (36.1% versus 19.1%; P=0.008) and disabling or fatal strokes (13.3% versus 6.3%; P=0.11). For surgically treated patients, the perioperative risk of hemispheric stroke was 1.1% in the presence of collaterals versus 4. 9% when absent. The 2-year stroke risks for surgical patients with and without collaterals were 5.9% versus 8.4%, respectively. Neither comparison in the surgical group was statistically significant. The observed reductions were independent of the degree of ICA stenosis and other vascular risk factors. CONCLUSIONS: Collaterals are associated with a lower risk of hemispheric stroke and TIA, both long term and perioperatively. Angiographic identification of collaterals assists in identifying patients with severe ICA stenosis at lower risk of stroke and TIA.     

Endogenous sex hormones and prostate cancer risk: a case-control study nested within the Carotene and Retinol Efficacy Trial.

To examine whether endogenous androgens influence the occurrence of prostate cancer, we conducted a nested case-control study among participants enrolled in the Carotene and Retinol Efficacy Trial. We analyzed serum samples of 300 cases diagnosed between 1987 and 1998, and 300 matched controls. Higher concentrations of testosterone (T) were not associated with increased prostate cancer risk. Relative to men with levels in the lowest fourth of the distribution, men in the upper fourth of total T had a risk of 0.82 [95% confidence interval (CI), 0.52-1.29]. The corresponding relative risks for free T (0.72; 95% CI, 0.45-1.14), percentage of free T (0.74; 95% CI, 0.46-1.19), and total T:sex hormone binding globulin ratio (0.52; 95% CI, 0.32-0.83) similarly were not elevated. Higher concentrations of androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were weakly associated with risk. Relative risks associated with being in the highest fourth for androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were 1.20 (95% CI, 0.76-1.89), 1.38 (95% CI, 0.86-2.21), and 1.27 (95% CI, 0.80-2.00), respectively. Men in the upper fourth of total estradiol (E2), free E2 and percentage of free E2 had relative risks of 0.71 (95% CI, 0.42-1.13), 0.52 (95% CI, 0.33-0.82), and 0.65 (95% CI, 0.40-1.05), respectively. The inverse association between E2 and prostate cancer risk was largely restricted to men with blood collection within 3 years of diagnosis. Our results add to the evidence that serum testosterone is unrelated to prostate cancer incidence. The suggestions that intraprostatic androgen activity may increase risk and that serum estrogens may decrease risk, warrant additional study.     

Induction of apoptosis in multi-drug resistant (MDR) human glioblastoma cells by SN-38, a metabolite of the camptothecin derivative CPT-11

 The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumors. Recent studies demonstrate that SN-38, a metabolite of the camptothecin (CPT) derivative CPT-11, has antitumor effects on several tumors, but the mechanisms responsible for its cytotoxicity remain unclear. We therefore determined whether SN-38 has cytotoxic effects on MDR human glioblastoma GB-1 cells and non-MDR human glioblastoma U87-MG cells. Furthermore, we determined what role SN-38 plays in the induction of cytotoxicity in these tumor cells. In this study, we demonstrated that SN-38 had significantly stronger antitumor effects on GB-1 and U-87MG cells than did CPT (P<0.01 and P<0.05, respectively). In addition, findings obtained using a DNA fragmentation assay, Hoechst 33258 staining, in situ end-labeling and cell cycle analysis demonstrated that SN-38 induced apoptosis in these tumors. Our results suggest that SN-38 has a stronger antitumor effect on malignant glioma cells regardless of MDR expression than does CPT, and therefore can be considered a new chemotherapeutic agent potentially effective in the treatment of human primary or recurrent malignant gliomas resistant to chemotherapy. Received: 6 October 1995/Accepted 29 June 1996     

The role of prostate-specific antigen (PSA) testing patterns in the recent prostate cancer incidence declinein the United States

Objectives: Trends in first-time and later PSA procedure rates are ascertained using longitudinal data from a population-based cohort. These trends are compared to trends in prostate cancer incidence to determine the role of PSA in the recent decline in prostate cancer incidence.Methods: Medicare data were linked with tumor registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. A 5 percent random sample (n=39985) of Medicare beneficiaries from the SEER areas without a previous diagnosis of prostate cancer as of January 1, 1988 was followed through 1994. Trends in first-time PSA use were distinguished from those of second or later for men without diagnosed prostate cancer.Results: Trends in the rate of first-time PSA procedures track closely with trends in prostate cancer incidence rates, increasing until 1992 and decreasing thereafter. Similar patterns were observed by race and age group. Geographic variability in the dissemination of PSA screening was observed, yet the association between testing and incidence remained. Men in the cohort had a 4.7 percent chance of being diagnosed within three months of an initial PSA test, with the percentage falling for subsequent tests.Conclusions: It is informative to distinguish first from later tests when assessing the effect of the diffusion of a test in a population. Taking this approach was useful in illuminating the role of PSA testing in a reversal of a long-term increase in prostate cancer incidence rates.