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Biomedical subjects

W Dubin

Publications and source records attributed to W Dubin.

13 recordsLinked to original sources

Bacterial endotoxin is an active component of cigarette smoke.

BACKGROUND: Chronic bronchitis in cigarette smokers shares many clinical and histologic features with environmental lung diseases attributed to bacterial endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhalation mimics many of the acute effects of cigarette smoke in the lower airway. Therefore, we reasoned that LPS may be a biologically active component of cigarette smoke. DESIGN: The Limulus amebocyte lysate (LAL) assay was used to measure LPS in the tobacco and filter tip components of unsmoked 1R4F experimental cigarettes and commercially available "light" cigarettes, as well as in mainstream (MS) and sidestream (SS) smoke particles generated with an automated smoking machine and collected on ventilator mainflow filters. SETTING AND PARTICIPANTS: Blood LPS activity and plasma cytokine concentrations were measured in groups of healthy smokers and nonsmokers who reported to the walk-in clinic at the Baltimore VA Medical Center for unrelated complaints. MEASUREMENTS: Blood LPS levels were measured by LAL assay and plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF receptors I and II (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay. RESULTS: Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8+/-1.0 microg/cigarette; light, 26.8+/-7.3 microg/cigarette [mean+/-SE]) and filter tips (1R4F, 0.67+/-0.55 microg/cigarette; light, 0.70+/-0.39 microg/cigarette) of cigarettes. Bioactive LPS was also detected in both MS (1R4F, 120+/-64 ng/cigarette; light: 45.3+/-16 ng/cigarette) and SS smoke (1R4F, 18+/-1.5 ng/cigarette; light: 75+/-49 ng/cigarette). Although systemic absorption of inhaled LPS may occur, we failed to detect any differences between nonsmokers and smokers in median blood LPS levels (median values, 66.75 and 72.1 pg/mL, respectively; p = 0.55) or plasma concentrations of TNF-alpha (0 vs 0 pg/mL, respectively; p = 0.71), sTNFR I(1,469 vs 1,576 pg/mL, respectively), sTNFR II (2,011 vs 3,110 pg/mL, respectively), or IL-6 (8.8 vs 0 pg/mL, respectively; p = 0.20). CONCLUSIONS: Smoking one pack of cigarettes per day delivers a dose of respirable LPS that is comparable to the levels of LPS associated with adverse health effects in cotton textile workers. Thus, we suggest that the bioactive LPS in cigarette smoke may contribute to the pathogenesis of chronic bronchitis that develops in susceptible cigarette smokers.

Bronchitis↗

Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study.

Rapid tranquilization is a routinely practiced method of calming agitated psychotic patients by use of neuroleptics, benzodiazepines, or both in combination. Although several studies have examined the efficacy of the three approaches, none have compared these treatments in a prospective, randomized, double-blind, multicenter trial. Ninety-eight psychotic, agitated, and aggressive patients (73 men and 25 women) were prospectively enrolled during an 18-month period in emergency departments in five university or general hospitals. Patients were randomly assigned to receive intramuscular injections of lorazepam (2 mg), haloperidol (5 mg), or both in combination. Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours, based on clinical need. They were evaluated hourly after the first injection until at least 12 hours after the last. Efficacy was assessed on the Agitated Behavior Scale (ABS), a modified Brief Psychiatric Rating Scale (MBPRS), Clinical Global impressions (CGI) scale, and an Alertness Scale. Effective symptom reduction was achieved in each treatment group with significant (P < .01) mean decreases from baseline at every hourly ABS evaluation. Significant (P < .05) mean differences on the ABS (hour 1) and MBPRS (hours 2 and 3) suggest that tranquilization was most rapid in patients receiving the combination treatment. Study event incidence (side effects) did not differ significantly between treatment groups, although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms. The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation.

Adolescent↗

Bronchoalveolar macrophage CD14 expression: shift between membrane-associated and soluble pools.

The bacterial endotoxin [lipopolysaccharide (LPS)]-binding protein CD14 modulates the host response to LPS, but membrane-associated and soluble forms of the molecule exert different biological effects. CD14 anchored to the mononuclear phagocyte membrane (mCD14) enhances response to LPS. Soluble CD14 (sCD14) may block LPS stimulation of CD14-bearing cells while supporting LPS presentation to non-CD14-bearing cells. We analyzed cell mCD14 and sCD14 expression in simultaneously collected human bronchoalveolar macrophages (BAM) and peripheral blood monocytes (PBM). Expression of mCD14 in freshly isolated BAM was only 9% as high as in PBM. Levels of sCD14 in 48 h in BAM culture supernatants were 19% as high as in PBM cultures. Interleukin (IL)-6 increased CD14 expression in both BAM and PBM but exerted different effects on CD14 distribution in these cell types. IL-6 increased only sCD14 release (2.5-fold) in BAM while increasing only mCD14 expression (2.5-fold) in PBM. IL-4 reduced both mCD14 (> 40%) and sCD14 (> 60%) expression in both cell types. We speculate that the balance between sCD14 and mCD14 expression influences the response to aspirated or inhaled LPS in the bronchoalveolar compartment. Cytokine expression and monocyte recruitment may influence this process by modulating CD14 expression.

Adult↗

Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment.

In allergic asthma, inhalation of antigen provokes an early increase in microvascular permeability with protein extravasation and a delayed recruitment of inflammatory cells. We showed that similar concentrations of lipopolysaccharide (LPS) are present in bronchoalveolar lavage fluid (BALF) in 12 subjects without asthma (86.5 +/- 53.8 pg/ml) and 12 subjects with mild asthma (111 +/- 37.0 pg/ml). These LPS levels are insufficient to stimulate cytokine release without accessory molecules. BALF obtained 24 h after segmental ragweed antigen challenge in 11 asthmatics allergic to ragweed contained increased levels of two LPS accessory molecules compared with preantigen BALF, 158-fold more LPS-binding protein (LBP) 4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03) and 31.6-fold more soluble CD14 (sCD14) (3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02). Postantigen BALF enhanced binding of fluorescein-conjugated LPS to CD14-bearing THP-1 cells and supported LPS-induced non-CD14-bearing endothelial cell expression of intercellular adhesion molecule-1 and interleukin-6, indicating functional LBP and sCD14. We suggest that extravasation of LBP and sCD14 into the bronchoalveolar compartment after antigen inhalation may enhance the capacity of inhaled or aspirated LPS to activate an inflammatory cascade that may amplify the inflammatory response to inhaled antigen in some asthmatics.

Acute-Phase Proteins↗

Quantitative EEG in elderly depressives.

Thirty-one elderly depressive patients were evaluated with topographic, quantitative EEG using relative measures, absolute measures, and computations of interhemispheric asymmetry and interhemispheric coherence in four frequency bands: delta, theta, alpha and beta. Patients were found to have lower than normal delta, higher than normal theta, higher than normal alpha and lower than normal beta values. EEG values were greater over the left than the right hemisphere in theta, alpha and beta bands. Lower than normal anterior interhemispheric coherence was found in all four frequency bands.

Aged↗

Geriatric psychiatry in the emergency department, II: Evaluation and treatment of geriatric and nongeriatric admissions.

The records of a hospital psychiatric emergency department were reviewed for elderly and middle-aged patients who were diagnosed with organic brain syndrome (OBS) or psychiatric disorder. These records were then compared with those of elderly patients from the medical emergency department. While elderly medical patients received routine physical evaluations and laboratory testing, elderly psychiatric patients with behavioral symptoms were often referred to psychiatry before they received tests necessary to differentiate physical disorders from functional psychiatric disorders. When tests were administered to psychiatric patients, many abnormal results were apparent, indicating the possible presence of physical disease. It is recommended that all elderly patients with psychiatric symptoms undergo adequate medical evaluations to screen for physical causes of the psychiatric symptoms.

Aged↗

Geriatric psychiatry in the emergency department: characteristics of geriatric and non-geriatric admissions.

A study was made of the Emergency Department records of 49 elderly (65 years old or older) and 49 middle-aged (40-64 years old) patients seen in an urban hospital's psychiatric emergency service. The data were compared for demographic and admission information, psychiatric treatment history, presenting complaints, symptoms, diagnoses, and final disposition status. For the elderly patients, the referral was more likely to be their first contact with psychiatric treatment, and they were more likely to be referred (accompanied) by family or friends than to be self-referred. Among the middle-aged patients, "substance abuse" (e.g., drugs, alcohol) disorders and schizophrenic disorders were more common. The elderly, however, were much more likely to be regarded as having an organic brain syndrome of unspecified cause (34.7 per cent vs 0). Access to treatment was fairly consistent for both groups as measured by the hospital's priority code, total time spent in the emergency department, and final disposition. These results raise important issues concerning the unique psychosocial characteristics and psychiatric treatment needs of elderly patients. This applies particularly to the emergency-department medical clearance of elderly patients with symptoms of organic brain syndrome.

Adult↗

Acquisition and generalization of instruction following behavior in profoundly retarded individuals.

Four profoundly retarded male residents of a state institution learned to comply with the instructions "come here," "stay," and "sit." Acquisition occurred in a special therapy room and instructions were presented in a fixed sequence. All subjects learned to comply with the instructions in the training environment. Testing occurred in the subject's ward dayroom where instructions were presented in a random sequence. Despite dramatic changes in the stimulus conditions associated with the transfer to the testing situation the subjects performed close to their asymptotic level. Three experimentally naive subjects participated in a second experiment which was similar to the first, except that the number of acquisition sessions and the number of trials per session were reduced. The reduction in number of acquisition trials did not appear to affect performance in the testing environment. The possibility of terminating off-task behavior of institutionalized individuals by eliciting previously acquired instruction following behavior was discussed.

Adolescent↗

Huntington's Chorea and dimethylaminoethanol (deanol).

Huntington's Chorea has multiple neurologic and psychiatric manifestations, and its treatment has been the subject of much debate. It appears that no single agent is effective for all patients with Chorea. Furthermore, different biochemical substances may be lacking in various Huntington's patients, i.e., gamma aminobutyric acid (GABA) in some, or a deficiency of acetylcholine (ACH) receptors in others. We approach this disease as a possible "spectrum illness," characterized by a relative deficiency of one substance, or a relative excess of another. If patients do not respond to one family of drugs, they may still benefit from a trial with another drug group.

Acetylcholine↗

Relationship between pretreatment electroencephalographic coherence measures and subsequent response to electroconvulsive therapy: a preliminary study.

Quantitative analyses of EEG recordings taken prior to a course of ECT in elderly depressed patients showed that normal anterior interhemispheric coherence in the delta frequency band was associated with more favorable clinical response to ECT, whereas lower coherence values were associated with incomplete therapeutic response. Clinical implications of these findings are discussed.

Aged↗