Asymmetric dimethylarginine blocks nitric oxide-mediated alcohol-stimulated cilia beating.

The airway epithelium is exposed to alcohol during drinking through direct exhalation of volatized ethanol from the bronchial circulation. Alcohol exposure leads to a rapid increase in the cilia beat frequency (CBF) of bronchial epithelial cells followed by a chronic desensitization of cilia stimulatory responses. This effect is governed in part by the nitric oxide regulation of cyclic guanosine and adenosine monophosphate-dependent protein kinases (PKG and PKA) and is not fully understood. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is implicated in the pathogenesis of several pulmonary disorders. We hypothesized that the inhibition of nitric oxide synthase by ADMA blocks alcohol-stimulated increases in CBF. To test this hypothesis, ciliated primary bovine bronchial epithelial cells (BBEC) were preincubated with ADMA (100 µM) and stimulated with 100 mM ethanol. CBF was measured and PKA assayed. By 1 hr, ethanol activated PKA, resulting in elevated CBF. Both alcohol-induced PKA activation and CBF were inhibited in the presence of ADMA. ADMA alone had no effect on PKA activity or CBF. Using a mouse model overexpressing the ADMA-degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH), we examined PKA and CBF in precision-cut mouse lung slices. Alcohol-stimulated increases in lung slice PKA and CBF were temporally enhanced in the DDAH mice versus control mice.

A systems analysis of a failure to test the effectiveness of waiting-list group therapy.

This nonexperimental effectiveness study attempted to evaluate the utility of a brief waiting-list group. The setting was a university clinic providing treatment for an inner-city population. Health delivery and staff dynamics made it difficult to conduct clinical research in this treatment-oriented setting. The nonrandom design allowed for patient choice, with few clients attending more than two group sessions, thus decreasing its impact. Managed-care pressures decreased staff cooperation with our research objectives, resulting in very low return rates in testing and follow-up data. A social systems analysis, highlighting staff and institutional ambivalence, is used to understand the failure to adequately test the effectiveness of waiting-list group therapy. Recommendations are offered to investigators who contemplate conducting clinical research with limited resources.

The waiting-list group.

This report describes a pilot study of a waiting-list group (preliminary process group [PPG]) that provided treatment for applicants to a university affiliated, urban mental health center. All individuals on the treatment waiting list were informed of the PPG. This semistructured group, meeting weekly, began with members presenting their problems, followed by free discussion, and ending with goal setting for the next week. Approximately one seventh (35 out of 262) of the clinic's applicants during a 4 1/2-month period chose to enter the PPG. They differed from those who chose not to participate (wait list) by being older and less educated. Approximately 80% of both wait-list and PPG participants subsequently entered therapy. Significantly more PPG patients than those on the wait list entered group treatment. The PPG served clinic needs by providing prompt service for self selected individuals and by supporting the group therapy program.

Correlation of in situ hybridization with histology and viral culture in patients with acquired immunodeficiency syndrome with cytomegalovirus colitis.

Endoscopic colonic biopsy specimens from 34 patients with acquired immunodeficiency syndrome and six patients without acquired immunodeficiency syndrome (3 were human immunodeficiency virus-seropositive and 3 were human immunodeficiency virus-seronegative) were examined by in situ hybridization for evidence of cytomegalovirus colitis and the results were compared with histologic examinations and viral cultures. In situ hybridization was positive in 22 of 25 patients with acquired immunodeficiency syndrome with histologic evidence of cytomegalovirus colitis. By our interpretation, 15 patients without cytomegalovirus colitis histologically all had negative hybridization studies. No correlation was found between in situ hybridization and viral culture results. In situ hybridization is a useful confirmatory test when the histologic changes are suspicious for cytomegalovirus but not considered diagnostic; it will only rarely demonstrate staining in a case considered negative histologically.

Dimensions of experiential learning at group relations conferences.

Four hundred and seventy-seven professionals attended thirteen group relations conferences. Conferences varied across three dimensions: context, including sponsorship and history: design, involving duration, intensity (residential setting) and complexity; and linkages, the social and authority ties between members and staff. Three month follow-up questionnaires were collected from sixty percent of participants. Significantly more self-assessed learning was reported by those who attended the residential than the non-residential conferences. The results, from a large diversified sample, suggest that a combination of training in a residential setting, strong institutional sponsorship and pre-existing authority and social linkages between members and staff resulted in the most reported learning. Group relations conferences provide unique learning opportunities for mental health professionals, (Correa et al. 1981) and have been increasingly used in the United States and Europe during the last twenty years. Despite this, there is little research evaluating the outcomes of such training in terms of member learning or the differential effectiveness of the alternative forms of conferences currently available. Conferences vary along three major dimensions: a) context, including the institutional sponsorship as well as the history of previous conferences held at the same site, b) design, including the duration, intensity and number of events which make up the conference, and c) linkages, the social and authority relations among members and staff. A review of the first decade of group relations work in the United States concluded that the characteristics of a conference, including the setting have an important impact on member learning, (Klein 1978).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of disseminated cytomegalovirus infection with 9-(1,3 dihydroxy-2-propoxymethyl)guanine: evidence of prolonged survival in patients with the acquired immunodeficiency syndrome.

Disseminated cytomegalovirus (CMV) infection is a common complication of the acquired immunodeficiency syndrome (AIDS) and contributes significantly to its morbidity and mortality. Dihydroxypropoxymethyl guanine, DHPG, is an antiviral agent that has been shown to inhibit CMV replication and to provide clinical benefit in patients with CMV infections, especially retinitis. In this study, the clinical characteristics, results of diagnostic evaluations, and survival were compared in 11 AIDS patients with disseminated CMV infections who were seen between August 1981 and October 1984 and were not treated with DHPG, and in 18 AIDS patients seen since that time who were treated with DHPG. The study groups were similar though the untreated group was somewhat more tissue depleted. Survival from diagnosis was significantly prolonged with DHPG therapy based upon life table analysis (p = 0.001). Therapy improved the quality of life, as 12 of 18 treated patients and only 2 of 11 untreated patients could be discharged from the hospital. Progression of CMV infection did not appear to play a role in the mortality of patients who died during DHPG therapy. We conclude that DHPG prolongs survival in patients with AIDS who have disseminated CMV infections.

Cytomegalovirus isolation from healthy homosexual men.

The acquired immune deficiency syndrome (AIDS) has focused renewed interest on cytomegalovirus (CMV) both as an infectious complication of the syndrome and as a potential etiologic agent in the pathogenesis of the immunosuppression. We studied 30 healthy homosexual men in New York City to determine the prevalence of virus excretion and its relationship to CMV-IgM antibodies and to T-lymphocyte subsets. Cytomegalovirus was detected in the urine and/or semen of 11 subjects. Eight of 11 CMV shedders were CMV-IgM positive, but CMV IgM was found in only one of 19 not shedding the virus. While homosexuals as a group had lower OKT4/OKT8 ratios (0.8 +/- 0.4, mean +/- SD) than heterosexual controls (1.8 +/- 0.4, mean +/- SD), there was no significant difference in ratios between homosexuals excreting virus and those not excreting virus. Cytomegalovirus excretion by homosexual men seems to be more prevalent than previously appreciated and may pose a significant risk for sexual transmission.

Enteropathy associated with the acquired immunodeficiency syndrome.

To explore the effect of the acquired immunodeficiency syndrome on gastrointestinal structure and absorption, the cases of 12 homosexual men with the syndrome and 11 homosexual controls were studied. Seven patients had diarrhea with weight loss. Bacterial or parasitic infections were not detected. All patients were malnourished; had significantly fewer T-lymphocyte helper and suppressor cells; and had significantly lower body weights, midarm circumferences, serum albumin concentrations, and iron binding capacities than homosexual controls. D-Xylose malabsorption and steatorrhea were present in patients, especially those with diarrhea. Jejunal and rectal biopsy samples were histologically abnormal in all patients with diarrhea. Jejunal abnormalities included partial villus atrophy with crypt hyperplasia and increased numbers of intraepithelial lymphocytes. Rectal abnormalities included intranuclear viral inclusions, mast cell infiltration in the lamina propria, and focal cell degeneration near the crypt base. The histologic findings suggest that a specific pathologic process occurs in the lamina propria of the small intestine and colon in some patients with the syndrome.