Prevalence of wasting in men infected with human immunodeficiency virus seeking routine medical care in an outpatient clinic.
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Biomedical subjects
Publications and source records attributed to L Rabeneck.
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The purposes of this research were to determine whether microsporidian infection is accompanied by structural alterations of the duodenal mucosa and to characterize the clinical and morphological evolution of intestinal microsporidiosis. In a previous systematic electron microscopic evaluation of mucosal biopsy specimens from patients with human immunodeficiency virus infection, we detected Enterocytozoon bieneusi in the duodenal tissue of 31 men. This report concerns a follow-up study of these 31 men, who underwent repeated clinical and laboratory evaluations, including repeated duodenal biopsies. Eighteen men had chronic diarrhea at enrollment and 13 had no diarrhea. The CD4+ cell counts (per mm3) ranged from 10 to 660 and were normal for three men. E. bieneusi infection was accompanied by a wide spectrum of histopathology of duodenal tissue; over a mean follow-up of 15 months, no consistent change in duodenal mucosal morphology was observed, and diarrhea did not invariably develop. These observations indicate that diarrhea and severe villus injury do not invariably accompany infection. Further studies are needed to determine the relationship between E. bieneusi infection and clinical illness.
BACKGROUND: Oesophageal candidiasis is the most common cause of oesophageal symptoms in patients with AIDS. Antifungal therapy, given as a suspension, may be better tolerated than capsules or tablets in children or patients with oesophageal symptoms. We performed a prospective study of the safety and efficacy of fluconazole suspension. METHODS: Patients with HIV infection; odynophagia, dysphagia, or retrosternal pain; endoscopic evidence of white plaques or exudate in the oesophagus; and microscopic confirmation of fungal infection on biopsy or brushing specimens were eligible. Patients received fluconazole oral suspension (200 mg loading dose followed by 100 mg q.d.s.). Therapy was continued for 2 weeks after symptom resolution. Repeat endoscopy was performed after completion of therapy. RESULTS: Forty-two patients enrolled in the study: 40 were male, mean (+/- s.e.) age was 37 +/- 2 years and mean CD4 cell count was 67 +/- 14/mm3. One patient was not evaluable because he received amphotericin during the first week of therapy. Symptoms resolved in all 41 evaluable patients; 17 (41%) had resolution by 1 week, 37 (90%) by 2 weeks, and 40 (98%) by 3 weeks. Endoscopic resolution occurred in 35 (95%) of 37 patients who underwent repeat endoscopy. Adverse events (skin rash in 1, nausea/vomiting in 2, elevated liver tests in 2) led to early termination of therapy in 5 patients, all of whom had clinical and endoscopic cure. CONCLUSIONS: Symptoms resolved in 100% of patients with AIDS and oesophageal candidiasis receiving an oral suspension of fluconazole, and 90% of patients had symptom resolution within 2 weeks. Determining whether the more rapid clinical cure in this study, compared with a previous trial which employed capsules, is related to an additional topical antifungal effect of the suspension, will require further study.
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The term acquired immunodeficiency syndrome (AIDS) enteropathy was first used in 1984 to refer to changes in intestinal structure and function in human immunodeficiency virus (HIV)-infected patients. Since then, confusion has arisen regarding the meaning of the term. To identify the sources of this confusion we performed a methodologic critique of published clinical research on the topic. We carried out a literature search to identify clinical studies that included at least 20 subjects. Among the six cross-sectional studies we identified, no consensus exists regarding the term itself, to whom it applies, the elements on which it is based, and the criteria for its definition. Further, methodologic problems pertaining to the selection of cases and controls limited the conclusions that could be drawn from these studies. Alterations of mucosal structure and function occur in some HIV-infected patients. However, the nature of these alterations and their relationships to symptoms (diarrhea), immune function, and enteric pathogens remain unclear. Further research is needed to develop a taxonomy for AIDS enteropathy. In carrying out this research, attention to methodologic issues will be important.
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An important determinant of patient outcomes is illness severity, which must be classified to guide clinical decision making and evaluate the effectiveness of diagnostic and therapeutic interventions. Currently, no widely accepted framework for grading illness severity in human immunodeficiency virus-infected patients exists. The best known classification systems for human immunodeficiency virus infection (Centers for Disease Control and Prevention; Walter Reed) are not based on illness severity, and provide stages that are not all inclusive so that a large number of persons cannot be classified (Walter Reed). Although much previous research has focused on individual prognostic factors (oral thrush, CD4 cell count, serum beta 2-microglobulin), little attention has been given to incorporating these factors into illness severity scales that are easy to use in clinical settings. In addition, despite the progressive functional disability of human immunodeficiency virus-infected individuals, few of the existing approaches to illness severity classification have examined the contribution of functional status. We urge investigators to develop clinically sensible severity scales that are easy to use. Such scales will considerably improve existing approaches that tend to rely solely on the CD4 cell count and do not take into account the known prognostic effects of other variables.
OBJECTIVE: To determine whether infection with Microsporidia leads to diarrhea in patients with human immunodeficiency virus (HIV) infection. DESIGN: Case-control study. SETTING: Primary care outpatient HIV clinic at a Veterans Affairs medical center. PATIENTS: One hundred six HIV-infected men, 55 with and 51 without chronic diarrhea. MEASUREMENTS: Each patient underwent upper endoscopy and flexible sigmoidoscopy to obtain duodenal, rectal, and sigmoid colonic biopsy specimens. At the time of endoscopy, a fresh stool was obtained for culture, ova and parasite assessment, and Cryptosporidium examination. Biopsy tissue was examined using electron microscopy to detect Microsporidia. RESULTS: The microsporidian parasite Enterocytozoon bieneusi was detected in the duodenal biopsy specimens of 31 of 106 men (29%); 24 of 106 men (23%) had other enteric pathogens. No significant difference was observed in the occurrence of microsporidiosis in patients with (18 of 55 [33%]) and without (13 of 51 [25%]) chronic diarrhea (odds ratio, 1.42; 95% CI, 0.61 to 3.31). A similar nonsignificant difference was observed after controlling for CD4 count and other enteric pathogens (odds ratio, 1.66; 95% CI, 0.68 to 4.06). Among patients with microsporidiosis, no difference was observed in the intensity of infection (defined by the presence of few, moderate, or abundant organisms) among cases and controls (P > 0.2). CONCLUSIONS: This is the first report to document the presence of E. bieneusi in HIV-positive patients without gastrointestinal symptoms. No significant difference was observed in the occurrence of E. bieneusi infection in HIV-infected patients with or without chronic diarrhea. Thus, the association between microsporidiosis and diarrhea, if one exists, may not be as strong as is currently believed.
OBJECTIVE: To develop a simple clinical staging system based on CD4 count and clinical variables that predicts progression to AIDS in HIV-infected non-AIDS patients. DESIGN: Retrospective cohort study. SETTING: A primary care outpatient clinic for HIV-infected patients at a VA Medical Center. PATIENTS: One hundred seventy-six HIV-infected non-AIDS patients seen at the Houston VA Special Medicine Clinic between January 1986 and December 1990 and followed for a mean of 22 months. Fifty-four patients (31%) progressed to AIDS during follow-up. MEASUREMENTS: The medical records were reviewed, and data corresponding to the initial (baseline) clinic visit and subsequent six-month visits were extracted. MAIN RESULTS: "Predictive" baseline variables (i.e., those associated with progression to AIDS) were first identified and then examined in Cox proportional hazards modeling. In the final model, CD4 category, oral thrush, and night sweats made significant independent contributions. A three-stage prognostic system was constructed by assigning points to the three variables: CD4 > 500 cells/mm3 = 0; 500 > or = CD4 > or = 200 = 1; CD4 < 200 = 2; presence of oral thrush = 1; presence of night sweats = 1. Stages were assigned as follows: stage I = 0 points, stage II = 1-2 points, and stage III = 3-4 points. The proportions of patients who progressed to AIDS were: stage I, 6/39 (15%); stage II, 31/106 (29%); and stage III, 17/31 (55%). CONCLUSIONS: These results demonstrate that simple, clinically sensible prognostic staging systems that predict progression to AIDS can be constructed using CD4 count and clinical variables.
PURPOSE: (1) To test the hypothesis that the clinical features of patients with acute pancreatitis could be used to construct a new prognostic staging system, and (2) to compare the new system with the results of the existing Ranson system based on age and laboratory data. PATIENTS AND METHODS: We obtained an inception cohort of 162 persons with 176 episodes of acute pancreatitis admitted to Yale-New Haven Hospital from January 1, 1987, to March 31, 1989. RESULTS: The main adverse outcome events, death and/or complications, occurred in 22% of episodes. Acute pancreatitis severity was classified in three stages, reflecting the presence of only primary features (no ileus or peritonitis), or the occurrence of secondary features that could be mild (mild ileus) or severe (severe ileus and/or peritonitis). In these 3 stages, the respective rates for outcome events were 13% (17 of 133), 43% (13 of 30), and 62% (8 of 13). The severity of comorbidity was classified according to Charlson's comorbidity index. For the 3 comorbidity stages, the outcome event rates were: minimal: 13% (12 of 92); intermediate: 22% (11 of 49); and severe: 43% (15 of 35). When the acute pancreatitis severity stages and comorbidity stages were conjoined to form the composite staging system, the corresponding outcome event rates were stage I: 8 of 107 (7%); stage II: 24 of 60 (40%); and stage III: 6 of 9 (67%). The composite staging system produced sharper gradients for the outcome events than Ranson's system, and was more readily applicable to all patients, particularly when the requisite special laboratory tests had not been ordered. CONCLUSIONS: The clinical and comorbid features of patients with acute pancreatitis can be used to construct a clinically "sensible" composite staging system. The stages are easy to use, require no additional or special laboratory tests, and predict more accurately than Ranson's system.
The intensity of diagnostic workup of patients with human immunodeficiency virus (HIV)-related chronic diarrhea is controversial. In the ideal setting in which an enteric pathogen is detected with minimal evaluation (stool tests) and in which specific treatment clears the diarrhea, eradicates the pathogen, and improves the patient's quality of life, the need for diagnostic workup is clear. However, problems frequently occur in the evaluation and treatment of patients that preclude such a straightforward approach. They are (a) failure to detect enteric pathogens; (b) detection of organisms of uncertain significance; (c) lack of effective treatment; (d) the presence of a severe coexisting illness that is the major determinant of the patient's outcome; and (e) lack of evidence that detecting enteric pathogens leads to improvement in broad patient outcomes, such as quality of life. I discuss these problems and examine the two opposing diagnostic workup strategies--minimal and intensive evaluation--that have been advocated. My main conclusion is that both approaches fall short, and that clinicians lack the information needed to guide clinical decision making. I urge investigators to analyze the full effects of alternative diagnostic interventions on broad patient outcomes so that clinical guidelines can be developed to assist the evaluation of patients.
This study was designed to assess the relative contributions of HIV transmission category and immunodeficiency to the risk of HIV-related diarrhea. We reviewed the medical records of 169 HIV-infected non-AIDS patients seen between 1986 and 1990 at the Houston VA Special Medicine Clinic. The prevalence of diarrhea at any given clinic visit ranged from 3% to 7%. Diarrhea was three times more common in homosexual/bisexual men [odds ratio = 3.0 (1.01-9.53)], and this pattern persisted when stratified by CD4 count. Previous studies have focused mainly on the detection of enteric organisms in patients with HIV-related diarrhea. Studies of the temporal relationships between sexual practices, enteric pathogens, diarrhea, and immunodeficiency are needed to clarify the pathogenesis of HIV-related diarrhea.
OBJECTIVE: To carry out an audit of hepatitis B immunization practices in an outpatient HIV clinic. METHODS: We reviewed the medical records of all new HIV-infected patients seen between October 1, 1990 and December 31, 1991. RESULTS: The 125 patients were men with a mean age and CD4 count of 43 yr and 240 cells/mm3, respectively. Fourteen percent (14%) of men who showed a clear need for vaccine, having no HBV markers, were not vaccinated by the clinic staff. Further, 16% whose susceptibility to HBV infection was unclear, with anti-HBc as a sole HBV marker, were not evaluated with a booster dose of hepatitis B vaccine in an attempt to elicit an anamnestic response. CONCLUSIONS: In failing to vaccinate or evaluate the 30% of patients without HBsAg or anti-HBs, our providers are missing an important opportunity in preventive medicine. We urge others to examine their own hepatitis B screening and vaccination practices.
To achieve the goal of validity, the randomized clinical trial has emerged as the scientific "gold standard" for evaluating therapies in clinical medicine. Regardless of how well randomized clinical trials are designed, however, problems often occur during the conduct of the trials that give rise to methodologic challenges in the analysis of results. Primarily two types of problems, changes in intended treatment and the failure to ascertain the study outcomes, occur during the conduct of randomized clinical trials. We studied the current analytic strategies that are used to deal with these problems and how the use of these analytic strategies can change the focus of the research so that the trial no longer answers the relevant question. To ensure that the right question is answered, new methods of design and analysis are required that balance the goals of validity and clinical pertinence.
In this paper we describe the results of oral therapy of esophageal candidiasis with clotrimazole vaginal tablets in 25 homosexual men with AIDS, of whom 19 had oral candidiasis and 16 had esophageal symptoms. Therapy with clotrimazole vaginal tablets, 100 mg, taken by mouth cleared the esophageal symptoms, oral candidiasis, and esophageal lesions completely in all 25 men. Clotrimazole vaginal tablets are a useful alternative to other antifungal agents for the treatment of esophageal candidiasis in AIDS patients.
INTRODUCTION: Helicobacter pylori (HP) in the gastric antrum has been strongly associated with both duodenal ulcer (DU) and chronic active gastritis (CAG). The relationship between HP and DU has been interpreted as causal by many observers. An alternate hypothesis is that HP coincidently colonizes CAG, which is independently associated with DU by some yet-unknown mechanism. PURPOSE: To assess the extent to which a causal relationship between HP and DU has been demonstrated, we performed a methodologic critique of published clinical studies. We carried out a literature search to identify clinical studies that included at least 25 subjects. Of the eight studies we identified, six used a cross-sectional design and two used a prospective cohort design. We applied methodologic criteria to assess causation: strength of association, biologic gradient, temporality, and experiment. METHODS: A strong association between HP and DU was demonstrated in all eight studies. Biologic gradient and temporality were not assessed in any study. In the two experimental studies of therapy, loss of antral HP was associated with a decreased rate of DU relapse; however, we did not interpret this as sufficient to support causality because the effect may have been due to a direct mucosal action rather than eradication of HP. CONCLUSION: We conclude that published evidence does not establish HP as a cause of DU. One approach to address causality would be an observational cohort study of ulcer relapse to assess the temporal relationships between HP, CAG, and DU.
We describe an acute human immunodeficiency virus (HIV) infection in 16 homosexual men who presented with painful swallowing (odynophagia). Eleven men had a maculopapular rash and 3 had palatal ulcers. At esophagogastroduodenoscopy (endoscopy), multiple discrete esophageal ulcers measuring 0.3 to 1.5 cm in diameter were observed. Electron microscopy of biopsy specimens taken from the ulcer margins in 8 men revealed viral particles 120 to 160 nm in diameter whose morphologic characteristics were those of retroviruses. Human immunodeficiency virus seroconversion was documented in 15 men by Western blot analysis. In 3 men, HIV-1 was isolated from peripheral blood mononuclear cells, in 2 men HIV-1 was isolated from peripheral blood monocytes, and in 1 man HIV-1 was isolated from tissue taken from the margins of the esophageal ulcers. These observations extend our knowledge of the clinical spectrum of acute HIV infection syndromes and suggest that cells in the esophagus are a target for HIV-1 infection.