A method for transition smoothing of sleep--waking states.

A method was developed for sequential redistribution of short-duration sleep--waking states into the long-duration behavioral state(s) that surrounds these intervals. This methodological approach is useful in determination of general sleep--waking patterns such as state durations, interstate intervals, and sleep--waking cycles. The redistribution sequences had no effect on total amount of sleep or waking categories, but did decrease stage 1 with successive redistribution steps. Examination of the slope of the curve (number of occurrences or mean epoch duration divided by successive redistributions) can be used to determine the appropriate "smoothing" for electroencephalogram (EEG) state data via location of the breakpoint in the curve. The low-pass redistribution technique has been particularly useful for smoothing large volumes of EEG state data for subsequent analyses without significantly changing the various sleep-waking states.     

The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis

BACKGROUND: Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. METHODS: We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. RESULTS: At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. CONCLUSIONS: In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.     

Reactive fibrohistiocytic proliferation simulating fibrous histiocytoma

A pelvic nodule was excised at the time of reexploration of the abdomen in a 32-year-old women who had previously had a malignant germ cell tumor with a mixed histologic pattern of the right ovary. The 3-cm firm lesion from the right vaginal apex was composed predominantly of spindle cells with a prominent storiform pattern. Some findings, such as the presence of foamy histiocytes and a focal foreign body reaction with polarizable material, were atypical for a lesion otherwise quite acceptable histologically as a fibrous histiocytoma. Ultrastructural findings also tended to support the reactive rather than neoplastic nature of this mass. There is a similarity to the silica reaction described by Weiss and co-workers (Cancer 42:2738-2743, 1978).     

Coordinated multivesicular release at a mammalian ribbon synapse

Traditional models of synaptic transmission hold that release sites within an active zone operate independently. Although the release of multiple vesicles (multivesicular release; MVR) from single active zones occurs at some central synapses, MVR is not thought to require coordination among release sites. Ribbon synapses seem to be optimized to release many vesicles over an extended period, but the dynamics of MVR at ribbon synapses is unknown. We examined MVR at a ribbon synapse in a retinal slice preparation using paired recordings from presynaptic rod bipolar and postsynaptic AII amacrine cells. When evoked release was highly desynchronized, discrete postsynaptic events were larger than quantal miniature excitatory postsynaptic currents (mEPSCs) but had the same time course. The amplitude of these multiquantal mEPSCs, which seem to arise from the essentially simultaneous release of multiple vesicles, was reduced by lowering release probability. The release synchrony reflected in these multivesicular events suggests that release within an active zone is coordinated during MVR.     

Genomic screen for loci associated with alcohol dependence in Mission Indians.

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain elusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians.     

Carcinoma of the lung and coexistent active pulmonary tuberculosis: diverse morphologic and radiographic presentations

Five patients with coexistent carcinoma of the lung and active tuberculosis within the same pulmonary lesion were studied. These cases represent five distinctly varying radiographic presentations and point out the extreme diversity of the morphological pictures of this particular disease combination. Physicians who regularly deal with patients who might present with either entity alone are cautioned to be alert to the possibility that these two diseases may be present simultaneously within single, specific pulmonary lesions.     

Decreased intraocular pressure and aqueous humor turnover rate during longitudinal ocular studies in the rabbit

One group of 5 pigmented rabbits, during a period of 10 weeks, and two groups of 8 albino rabbits, during 16 weeks, showed a fall in aqueous turnover rate and outflow facility of about 30%. A fall in intraocular pressure also occurred of about 10 mm Hg. The biochemical correlative mechanism, systemic and/or local, is conjectural (reduction of "stress"; homeostasis). Empirically a parallel completely untreated control group should accompany any longitudinal study group in order to differentiate these temporal trends from experimental effects.     

Identifying men at high risk of heart attacks: strategy for use in general practice

A strategy was devised for identifying men at high risk of acute myocardial infarction or sudden ischaemic death. A risk score was devised using cigarette smoking, mean blood pressure, recall of ischaemic heart disease or diabetes mellitus diagnosed by a doctor, history of parental death from "heart trouble," and the presence of angina reported on a questionnaire. The top fifth of the score distribution identified 53% of ischaemic heart disease cases--that is, men who subsequently experienced major ischaemic heart disease over the next five years. The addition of serum total cholesterol concentration and electrocardiographic evidence only slightly improved prediction (to 59%) and would have considerably increased the cost and effort of screening. Using this risk score on an opportunistic basis could be particularly valuable in general practice. Management of this high risk group is regarded as appropriate medical care and is complementary to the population approach to preventing ischaemic heart disease. Such a strategy for reducing the incidence of and mortality from ischaemic heart disease in men at high risk would also increase professional and public awareness of the need for preventive action.     

Vegetable consumption and blood lead concentrations.

Women resident in an area heavily contaminated by spoil from old lead mining have blood lead concentrations that are about 50% higher (p less than 0.001) than those of women living in a "control" area some distance away. Blood lead concentrations were related to the consumption of home grown produce. Those with the highest consumptions had blood lead concentrations that were 28% higher (p less than 0.001) than those of women who consumed no locally grown vegetables. Nevertheless, in the total population in the area this effect seemed likely to account for only about 5% of the population mean blood lead concentration. The data suggested that an increase in soil lead of 1000 micrograms/g is associated with an increase in blood lead of about 0.20 microM/1 (4.2 micrograms/dl).