Ethical modifications of the Emergency Drug Release Program for AIDS: a proposal.
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Biomedical subjects
Publications and source records attributed to M J Gill.
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The presence of immunoreactivity to the neuronal phosphoprotein B-50 and the peptides bombesin, calcitonin gene-related peptide, galanin, neurotensin, neuropeptide Y, somatostatin, substance P, and vasoactive intestinal polypeptide was examined in biopsy specimens from the duodenum and rectum of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative male homosexual patients. The distribution of B-50 and the peptides was correlated with HIV serology, number of CD4+ lymphocytes, and the presence of HIV in biopsy culture. There was a very low incidence of enteric pathogens in both groups of patients. It was found that HIV-seropositive patients had a greater incidence of abnormal patterns of immunoreactivity (reduced intensity and/or density of innervation) in enteric nerves and enteroendocrine cells than HIV-seronegative patients. A reduction of substance P immunoreactivity was significantly correlated with reduced CD4+ lymphocyte count and HIV status; a similar trend was also seen for somatostatin and vasoactive intestinal polypeptide. Using B-50 as a marker, it was found that both groups of patients had altered patterns of immunoreactivity in rectal nerves. The findings of this study suggest that some of the clinical symptoms associated with HIV infection may be caused by a specific HIV enteropathy that influences enteric nerve and/or enteroendocrine cell function by altering the density of peptide immunoreactivity.
OBJECTIVE: To determine the prevalence of HIV in endoscopic biopsies from the esophagus, stomach, duodenum, and rectum of homosexual and bisexual men at various stages of HIV infection as part of a comprehensive study of gastrointestinal dysfunction in HIV infection. METHODS: After repeated washings and mechanical disruption, biopsies obtained from 58 volunteers were individually cocultured with pooled peripheral blood lymphocytes from healthy HIV-seronegative blood donors. RESULTS: HIV was isolated from at least one site in 40 out of 49 patients. Esophageal biopsies were most frequently found positive (46%), followed by duodenal biopsies (44%), rectal biopsies (43%), and gastric biopsies (27%). Recovery of HIV was not related to any gastrointestinal signs or symptoms. HIV was recovered in the biopsies both from asymptomatic patients with CD4 lymphocyte counts greater than 500 x 10(6)/l and also from patients with more advanced disease receiving zidovudine therapy. CONCLUSIONS: The entire gastrointestinal tract appears to be a target site throughout the course of HIV infection in homosexual and bisexual men.
Blood sampling on filter paper has many advantages for the detection of perinatal human immunodeficiency virus (HIV) infection by the polymerase chain reaction (PCR). However, if the method is to be widely used, an assessment of its performance under field conditions is required. To simulate conditions in the field, 50-microliters aliquots of whole blood containing low levels of HIV proviral DNA (4 to 1,024 copies per 100,000 nucleated cells) were spotted onto filter paper; dried; and subjected to heat, humidity, and prolonged storage at room temperature. After exposure, the DNA was recovered and amplified with primers to human leukocyte antigen DQ alpha- and HIV-specific sequences. Treatment at 37 degrees C and 60% humidity for 7 days, storage for 12 weeks at 22 degrees C, and freeze-thawing twice had no adverse effect on PCR reactivity when compared with the results obtained with reference spots stored at -20 degrees C. The lower limits of HIV detection in all tests ranged from 4 to 16 HIV copies per 100,000 cells. Fixation in 70% ethanol improved the amplification of low levels of HIV DNA and reduced biohazard risks. These findings suggest that dried blood spots will provide a powerful new resource for testing for HIV by PCR, especially in remote areas where refrigeration and immediate sample processing are unavailable.
A psychiatric examination was conducted on 144 patients at various stages of HIV infection and on 29 controls found to be seronegative. One-half of the control group had at least one DSM-III-R Axis I diagnosis, most commonly cannabis abuse, alcohol abuse, or adjustment disorder. Compared to this baseline, HIV-infected subjects had higher rates of adjustment disorder. AIDS patients were also more likely to suffer from organic mental disorder. The rate of unemployment increased as the disease progressed. Major depression was seen in only ten patients, and there were no differences between controls and HIV-infected subjects. Formal assessment of mood state and feelings of pessimism also showed no differences among the groups. The importance of helping improve the patient's lifestyle through the control of alcohol and drug abuse is underscored.
49 gay men confirmed to be infected with the human immunodeficiency virus (HIV) and 9 HIV seronegative gay men participated in a pilot study comparing clinical status and enteric parasite load with gastrointestinal structure, function and symptomatology. Cases included 16/49 (33%) men who were CDC stage II, 7/49 (14%) who were CDC stage III, and 26/49 (53%) who were CDC stage IV. The mean CD4-lymphocyte count was 476 +/- 199 (SD)/microliter. The prevalence of enteric parasitic flora was similar in HIV seropositive patients and controls. Seven cases had enteric infection with pathogenic agents including 3 patients with Entamoeba histolytica, and 4 patients with Giardia lamblia, one of whom also had cryptosporidiosis. Other cases were most frequently colonized with Blastocystis hominis (44%) and Endolimax nana (41%) regardless of the HIV clinical status. HIV seropositive patients with enteric parasitic colonization tended to have lower mean levels of serum IgA than cases without parasites. Duodenal morphometric mucosal changes demonstrated a significant decrease in the mean villous height (p < 0.01) with no elongation of the crypt depth in HIV-infected patients with and without diarrhea compared to controls. Despite gastrointestinal symptoms including diarrhea and weight loss being more prevalent in HIV infected individuals than controls, no correlations were found between the presence of particular enteric parasites, gastrointestinal symptomatology, the clinical HIV status of the CD4-lymphocyte count, the malabsorption of D-xylose or morphometric changes in the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)
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We describe a unique case of Pneumocystis carinii organisms within a peritoneal effusion of a patient with acquired immunodeficiency syndrome (AIDS). The patient, a 28-yr-old homosexual male with profound immunosuppression, presented with splenomegaly and ascites. A peritoneal tap was performed for diagnostic purposes. Cytologic examination of the cytospin specimen showed reactive mesothelial cells along with aggregates of debris reminiscent of the foamy exudates seen in the alveoli of lungs infected with the Pneumocystis carinii organism. A modified methanamine silver stain was performed and revealed the presence of scattered Pneumocystis carinii in the specimen. Extrapulmonary Pneumocystis carinii infection is occasionally seen in AIDS, but we could find no other reports of its detection in peritoneal fluid.
Mothers of 60 children with autism participated in this study to measure the effects of social support and hardiness on the women's responses to the stressful demands of raising a child with a disability. MANOVA analysis indicated a significant main effect for hardiness, Wilks' lambda = .859, approx. F(2, 55) = 4.494, p less than .02. There were no main effects for social support, or for the interaction of social support and hardiness. In regression analyses, the best combination of predictors of depressive symptoms were the Commitment dimension on the Hardiness Questionnaire and the total score on the Interpersonal Support Evaluation List social support inventory, mult. R = .783, p less than .001. The best predictor of somatic complaints was total Hardiness score, mult. R = .698, p less than .01. There was a significant correlation between hardiness and perceived social support, r(57) = -.67, p less than .001. Results are discussed in terms of the relationship between perceived social support and hardiness and the potential buffering effect of these dimensions.
This paper explored the extent to which the use of mild versus strong aversives in programs for clients with autism affected the degree of job stress reported by direct care staff on the Maslach Burnout Inventory. The subjects included 56 staff from programs using only mild aversives and 60 staff from programs using strong aversives. Subjects anonymously completed the inventory and mailed it directly back to the researchers. The most significant finding was that direct care staff in facilities which permitted the use of strong aversives reported more intense feelings of personal accomplishment on the inventory than did subjects whose programs were limited to the use of mild aversives. Furthermore, there was a significant relationship among the personal use of strong aversives, number of years in the field, and the intensity of Personal Accomplishment. These findings suggest that allowing staff to use a wide range of interventions including strong aversives may diminish job stress and enhance one's sense of personal efficacy.
Treatment for recurrent genital herpes using edoxudine 3% cream for 5 days was evaluated in 200 patients in a randomized, multicenter, double-blind, placebo-controlled, clinic-initiated trial. Lesion tenderness was predictive of and more sensitive and longer-lasting than the symptom of pain. Among patients receiving placebo, times to crusting (P = .043), cessation of investigator-observed signs (P = .005), lesion-associated signs (P = .02), and groin signs (P = .05) were longer in women. Edoxudine reduced viral shedding in men (mean 2.7 vs. 3.4 days, P = .009) and women (2.0 days vs. 3.5 days, P = .0001). Loss of investigator-observed signs (4.4 vs. 6.2 days, P = .002), investigator-observed lesion tenderness (P = .01), lesion signs (P = .02), groin adenopathy (P = .01), and tenderness (P = .01) occurred earlier in women taking edoxudine. Edoxudine was well-tolerated and reduced several signs of herpes in women. Its clinical role in recurrent genital herpes remains to be fully determined.
Acyclovir was evaluated as treatment of recurrent herpes simplex virus type 2 infection of the hand in a double-blind, placebo-controlled crossover study. In nine fully evaluable patients, oral acyclovir (2 g/day in three doses for 10 days) initiated during the earliest phase of a recurrence reduced the mean durations (+/- standard deviation) of clinical symptoms from 10.1 (+/- 3.6) to 3.7 (+/- 3.0) days (P = 0.008), signs from 11.1 (+/- 3.7) to 6.2 (+/- 3.3) days (P = 0.024), and viral positivity from 5.3 (+/- 3.8) to 0.6 (+/- 1.1) days (P = 0.011).
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Over the last 10 years Rhodococcus equi has been identified as an important, albeit very rare, opportunistic pathogen. As the number of patients immunocompromised from HIV infection grows, this microorganism will likely become of increasing clinical importance. Infection with R. equi is usually insidious, causing progressive pulmonary disease that is typically pleural based at the time of microbiological diagnosis. As in the case we present, the clinical and microbiological diagnoses may be significantly delayed, either by the common pitfalls encountered in the laboratory identification of R. equi, or by the failure to recognize the pathogenic potential of the isolate. R. equi infection should be suspected in immunocompromised patients with pneumonia, when a pure or predominant growth of aerobic, non-sporeforming gram-positive bacilli is found on cultures of bronchoalveolar lavage fluid and other pulmonary pathogens have been excluded.
We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy.
In subjects with normal renal function, acyclovir is rapidly removed from the body via the kidneys. In subjects with end-stage renal disease, the half-life is significantly prolonged. The half-life in subjects receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) is similarly prolonged (10.0 +/- 2.2 and 13.2 +/- 4.7 hours, respectively). After intravenous dosage, peritoneal clearance was 3.4 +/- 0.2 mL/min. Intraperitoneal dosing in subjects receiving CAPD resulted in a bioavailability of 61 +/- 10% and drug levels sufficient to inhibit herpes simplex virus (HSV) and varicella zoster virus (VZV). Intraperitoneal administration is an alternative route of administration in patients with poor vascular access.
The first episode of herpes simplex virus (HSV) infection of the hand can occur in association with infection at another site, such as primary HSV-1 gingivostomatitis. Autoinoculation is the likely route of transmission. The attacks are usually solitary and last about 14 days. A first episode that results from exogenous inoculation may be severely inflammatory and may last up to 28 days. The majority of cases are recurrent infections and most often occur in adults with HSV-2 infection.
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