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Biomedical subjects

B L Cook

Publications and source records attributed to B L Cook.

At least 19 recordsLinked to original sources

The military environment: risk factors for women's non-fatal assaults.

Little is known regarding environmental exposures for non-fatal violence toward women in the workplace. We sought to identify factors associated with non-fatal physical assault occurring to women during military service. A cross-sectional telephone survey of a national sample of 558 women veterans who served in Vietnam and subsequent eras of military service was conducted; 537 women were interviewed. Twenty-three percent experienced non-fatal physical assault during military service. Rates of assault were consistent across eras of service. Military environmental exposures, including sexual harassment allowed by officers (P < 0.0001) and unwanted sexual advances while on duty (P < .0001) and in sleeping quarters (P < 0.0001), were independent risk factors for assault. Environmental factors in the military workplace, including leadership behavior, appeared to promote violence toward military women. Such occupational factors can be identified and should be eliminated.

Accidents, Occupational↗

E2F is required to prevent inappropriate S-phase entry of mammalian cells.

E2F is a family of transcription factors that regulates the cell cycle. It is widely accepted that E2F-mediated transactivation of a set of genes is the critical activity that governs cellular progression through G(1) into S phase. In contrast to this hypothesis, we demonstrate that E2F actually suppresses the onset of S phase in two cell types when the cells are arrested by gamma irradiation. Our findings indicate that in these cells, the critical event triggering progression from G(0)/G(1) arrest into S phase is the release of E2F-mediated transrepression of cell cycle genes, not transactivation by E2F. Furthermore, our data suggest that E2F-mediated transactivation is not necessary for the G(1)/S-phase transition in these cells.

Animals↗

Ethanol and natural killer cells. I. Activity and immunophenotype in alcoholic humans.

The human lymphocyte fraction with the greatest fresh killing activity against K562 targets is phenotypically the CD3-CD19-CD56+ subset. There have been reports of reduced natural killer (NK) activity in human alcoholics, but overall consistency is lacking and phenotypic monitoring has been inadequate to allow reliable estimates of changes in the active cell fractions. We have evaluated a range of cell surface markers and fresh NK activity in controls and alcoholics, and now report abnormalities in both phenotype and function in some alcoholics, but a normal profile in others. Patients without evidence of active liver disease (AWLDs) tend to have normal fresh basal activities and phenotypic profiles. Patients with alcoholic liver disease (ALDs) have fewer Lin- lymphocytes that are CD56+. Three of 14 ALDs assayed in the present work had absent NK activity, whereas others were activated. In normal controls and in AWLDs, the presence of monocytes in the lytic assay consistently inhibits lysis; but, in some patients with ALD, the presence of monocytes is stimulatory to NK activity. In alcoholics as one group, there is a statistically significant relative increase in a novel Lin- subset of unknown function; this subset has a phenotype of Lin-CD56-CD45RO+.

Adult↗

Loss of the CD5+ and CD45RAhi B cell subsets in alcoholics.

Chronic alcoholics are frequently immunodeficient, have polyclonal hypergammaglobulinaemia, and often have autoantibodies. Recent work in other diseases has shown that functional distinctions of possible relevance to autoimmunity and immunodeficiency can be found among the B cell subsets defined by differential expression of the surface markers CD5 and CD45RA. Therefore, we have evaluated the CD5, CD45RA B cell subsets of both chronic alcoholics without evidence of active liver disease (AWLD), and alcoholics admitted for acute alcoholic liver disease (ALD). Mean B cell numbers were normal in AWLD, but significantly reduced in ALD. Analysis of B cells by three-colour flow cytometry in 20 patients and 29 controls revealed a sharp decrease in the percentage of alcoholics' B cells which were CD5+, 37.6% versus 16.3%, P < 0.000 01; absolute CD5+ B cell numbers were similarly reduced (58.9 cells/microliters versus 20.9; P = 0.0012). In addition to the loss of CD5+ B cells, there was a reduction in the percentage of B cells which are CD5- CD45RAhi, leaving many patients with a B cell profile which was predominantly CD19+ CD5- CD45RAlo. This subset appears phenotypically similar to the IgM-producing CD5- CD45RAlo subset described by others, and may be enriched for autoantibody-producing cells. One outlier patient was an ALD with 61% of B cells which were CD5+, which also is a profile consistent with increased autoantibody production.

Alcoholism↗

Diazepam versus alprazolam for the treatment of panic disorder.

BACKGROUND: Alprazolam has proven efficacy as a treatment for panic disorder, but the place of other benzodiazepines is less well established. METHOD: To compare the efficacy and tolerability of diazepam and alprazolam for the disorder, a placebo-controlled, double-blind trial was undertaken in two sites. Two hundred forty-one subjects with panic disorder or agoraphobia with panic attacks were randomly assigned to flexible doses of diazepam, alprazolam, or placebo for 8 weeks. RESULTS: At the end of the trial, over 60% of subjects taking either diazepam or alprazolam were at least moderately improved compared with less than 30% of those taking placebo. On all measures of efficacy, subjects taking diazepam and alprazolam showed an equally favorable response. Despite some sedation early in the trial, both drugs were tolerated well. More severely ill subjects responded less well to either benzodiazepine. CONCLUSION: The results indicate that diazepam is an effective alternative to alprazolam for the treatment of panic disorder.

Adult↗

Modulation of T-cell adhesion markers, and the CD45R and CD57 antigens in human alcoholics.

Direct and indirect evidence indicates that T cells are altered in alcoholics. The most commonly reported changes under direct examination have been consistent with an increased level of activation as reflected by shifts in the ratio of common leukocyte antigen isoforms expressed at the cell surface, by increases in the expression of class II antigen, or by alterations in the expression of various adhesion molecules. Functional evidence for T-cell abnormality includes loss of delayed hypersensitivity and a number of findings attributed to dysregulation of B cells by alcoholic T cells; these include the widely reported distrubances of immunoglobulin production in vivo and a range of abnormal responses when T and B cells are combined in vitro. Detailed flow cytometric examination of T cells from alcoholics with or without active liver disease reveals a significant loss of L-selectin CD8+ T cells, but not usually of CD4+ T cells. There is an inverse increase in the expression of CD11b on the CD8+ cells that have decreased L-selectin+ percentages. Both CD8+ and CD4+ T cells in alcoholics display a significant loss of the CD45RA isoform and a gain of cells exhibiting the CD45RO isoform. Other surface alterations include increased expression of CD57, a marker most commonly associated on T cells with conditions of chronic increased antigenic exposure. It is argued that these and other T-cell alterations in alcoholics are cytokine-driven in part and result in T-cell differentiation states that are functionally inappropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Delusional infestation. The interface of delusions and hallucinations.

Delusional infestation represents a unique subtype of the delusional disorder category. This article presents the phenomenology, etiology, and treatment of delusional infestation. This article also reviews historical and theoretical attempts to distinguish tactile sensory phenomena as either hallucinations or delusions.

Delusions↗

Fine T-cell subsets in alcoholics as determined by the expression of L-selectin, leukocyte common antigen, and beta-integrin.

Alcoholics admitted to the hospital solely for detoxication have been studied by flow cytometry to evaluate changes in the surface markers of peripheral blood leukocytes. As we have shown previously, such patients have an elevated percentage of CD8hi lymphocytes that are HLA DR+; we now demonstrate that they also have striking alterations in the quantitative relationships of the fine T-cell subsets. Both CD4+ and CD8hi lymphocytes have a sharply reduced percentage of the L-selectin+ CD45RA+ subset, increased percentages of the CD45RA- subsets, and several other fine subset alterations. The fine subset profile suggests, according to current correlations of phenotype and function, that both CD4+ suppressor inducer and CD4-dependent CD8+ suppressor effector cells are reduced, whereas other subsets, including CD8+ CTL or their precursors, are increased in relative percentages. Some of the phenotypic changes are reversible over the several days following withdrawal. In other results, the percentage of CD8hi lymphocytes epxressing CD11b (beta-integrin) is shown to be reciprocal with the percentage expressing L-selectin both in normals and alcoholics. However, the regression function of CD11b vs. L-selectin on CD8hi cells is different for the alcoholics than for the normals, indicating an abnormality in the regulation of the expression of these two adhesion markers. Taken together, this abnormality of adhesion molecules and the fine subset alterations previously described indicate widespread changes in the peripheral lymphocytes of currently drinking alcoholics. These changes suggest functional deficiencies that may include alterations of lymphocyte traffic and other adhesion-dependent functions, and a shift in the balance of regulatory interactions.

Adult↗

Identification of treatment-resistant depressives who respond favorably to carbamazepine.

Thirteen depressed patients with documented histories of failure to respond to tricyclic antidepressant medications who reported multiple partial seizure like symptoms were given open trials of carbamazepine. Eleven of the 13 showed moderate to substantial improvement in affective status that was accompanied by significant mean changes on the Beck or Hamilton depression scales. In addition, the mean number of reported partial seizure-like symptoms decreased significantly with treatment. Dichotic word listening performance was the only neuropsychological variable that was impaired at baseline and was also the only cognitive performance that improved following treatment. These preliminary observations suggest that there is likely to be a subgroup of treatment-resistant, carbamazepine-responsive depressives who can be identified by evaluating for the presence of multiple partial seizure-like symptoms.

Adult↗

Generalized anxiety disorder vs. panic disorder. Distinguishing characteristics and patterns of comorbidity.

In order to examine the validity of the distinction between generalized anxiety disorder (GAD) and panic disorder (PD) we compared 41 subjects with GAD and 71 subjects with PD. The GAD subjects had never had panic attacks. In contrast to the symptom profile in PD subjects suggestive of autonomic hyperactivity, GAD subjects had a symptom pattern indicative of central nervous system hyperarousal. Also, subjects with GAD had an earlier, more gradual onset of illness. In terms of coexisting syndromes, GAD subjects more often had simple phobias, whereas PD subjects more commonly reported depersonalization and agoraphobia. GAD subjects more frequently had first-degree relatives with GAD, whereas PD subjects more frequently had relatives with PD. A variety of measures indicated that our GAD subjects had a milder illness than those with PD. Also, fewer GAD subjects gave histories of major depression than did PD subjects. Among GAD subjects, coexisting major depression was associated with simple phobia and thyroid disorders and among PD subjects, comorbid depression was associated with social phobia and hypertension. Our findings indicate that the separation of GAD from PD is a valid one. They also indicate that, within disorders, unique patterns of comorbidity may exist that are important both clinically and theoretically.

Adult↗

Alcoholism and the D2 receptor gene.

The allelic association of the human dopamine D2 receptor gene and alcoholism was evaluated in 20 male alcoholics and 20 controls (sex, race, and geographic place of birth matched). This study further examines the issue of alcoholism severity and A1 allele frequency. No difference in A1 allele frequency was observed between these two groups. Similarly, no relationship between alcoholism severity and A1 frequency within the alcoholics was demonstrated.

Adult↗

Depression and previous alcoholism in the elderly.

A prospective study of male in-patients over 55 years old who met Feighner criteria for non-bipolar depression was performed to determine if a previous history of alcoholism significantly influenced treatment or response to treatment. Among 58 subjects with complete follow-up information, the 16 who had a history of alcoholism had a presentation at index which differed from that of the non-alcoholics, and on follow-up they clearly had more chronic illness. This elderly sample with alcoholism resembles 'neurotic-reactive' depressives described in younger samples, and supports a past history of alcoholism as being a risk factor for chronicity of depression on follow-up in the elderly population.

Aged↗

Anxiety and the menstrual cycle in panic disorder.

Nineteen females with panic disorder were studied using daily prospective home diary ratings of various general health related items, a short anxiety self-rating scale, a survey of late luteal phase dysphoric symptoms, as well as a record of the number and severity of panic attacks. The subjects collected information for 60 consecutive days, and information regarding 30 menstrual cycles was available for analysis. Overall, subjects retrospectively reported increases in their anxiety symptoms during premenstrual days, but this was not demonstrated consistently on daily prospective ratings.

Adult↗

A retrospective study of compliance with recommended hematologic monitoring of carbamazepine.

Early case reports of fatal hematologic effects associated with carbamazepine (CBZ) resulted in manufacturer recommendations for extensive laboratory monitoring. Several alternative monitoring protocols have been published, indicating disagreement with those recommendations. The manufacturer has removed specific monitoring guidelines allowing physicians to monitor CBZ during treatment based on their clinical judgment. This study was designed to determine the frequency of CBZ hematologic monitoring in one academic setting. Data on complete blood counts (CBCs) were retrospectively obtained and were compared with 1975-88 Physicians' Desk Reference recommendations for weekly CBCs during the first three months of treatment. Eighty-three patients were identified: 32 psychiatry, 37 neurology, and 14 from other clinics. Only one patient met guidelines for monitoring during the entire first three months of treatment. Comparisons between clinics demonstrated no statistically significant differences in monitoring rates. Prospective studies in academic and private practice settings are needed to provide more information on actual monitoring practices. Due to the removal of specific manufacturer recommendations, a standard approach is needed to establish consistent and adequate monitoring and to provide legal support to prescribers.

Adult↗

A review of carbamazepine's hematologic reactions and monitoring recommendations.

Early case reports of fatal hematologic effects attributed to carbamazepine (CBZ) resulted in extensive monitoring recommendations by the manufacturer. The rarity of blood dyscrasias led many authors to question the manufacturer's guidelines. Thus the manufacturer removed specific monitoring guidelines, allowing physicians to monitor CBZ using their clinical judgment. This article reviews case reports and studies of CBZ's hematologic effects. Due to their rapid onset, daily laboratory checks would be necessary to monitor for aplastic anemia, agranulocytosis, and thrombocytopenia. These adverse effects are best monitored by informing patients and physicians to carefully watch for signs and symptoms. Leukopenia develops more slowly, occurring in approximately 12 percent of children and 7 percent of adults. Its onset is typically within the first three months of treatment, with patients at risk having a low or low-normal pretreatment white blood cell (WBC) count. Leukopenia often reverses, even if CBZ is continued. Based upon our review of the literature, we recommend monitoring of those high-risk patients during the first three months of treatment with the frequency being determined by results of each laboratory value. WBC counts less than 3000/mm3 or neutrophil counts below 1000/mm3 warrant a decrease in dose with frequent monitoring or CBZ discontinuation, if necessary.

Adult↗

Perspectives on bipolar illness.

Based on evidence available at present, it appears that heterogeneity does exist within bipolar disorder. Persons with mania differ in family history of affective illness, their age at the onset of illness, sex, and organic cause and course of the illness. The question of how these variables influence an individual's response to treatment has never been systematically studied. Multicenter trials of the various antimanic agents need to be conducted to determine whether the various subgroups of manic patients have different pharmacological response profiles. At present, the clinical management of mania is best approached using lithium carbonate in a dosage adequate to achieve a 12-hour serum lithium level to 1.0 to 1.2 mEq/L. The time to response is usually 2 to 3 weeks, and during this period an antipsychotic or benzodiazepine agent may be added to help control symptoms such as agitation or sleeplessness. Prophylactic maintenance with 12-hour serum lithium levels between 0.8 and 1.0 mEq/L should be used for at least 6 to 12 months after resolution of the manic episode. In patients with more than one episode, lithium maintenance therapy may need to be continued indefinitely. In patients who are not responsive to lithium, the most prominent alternative therapies include anticonvulsants and calcium-channel blocking agents. Anticonvulsants (e.g., carbamazepine, valproic acid, clonazepam) are generally first used as alternative therapy (either alone, or in combination with lithium), followed by a calcium-channel blocker (e.g., verapamil). Clinical practice would generally suggest first using the alternative agent alone, then adding lithium if response is inadequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticonvulsants↗