Treatment of American cutaneous leishmaniasis: a comparison between low dosage (5 mg/kg/day) and high dosage (20 mg/kg/day) antimony regimens

There is debate about the margin of normal tissue that should be included with excisions of melanocytic lesions of the skin, and about which lesions should be referred for specialist care. We describe the determinants of the margins of excised melanocytic skin lesions and of referral patterns from primary care. Copies of the pathology reports of melanocytic skin lesions excised from two cities in tropical Queensland were obtained; questionnaires about each lesion were administered to the excising doctor. Data about 3275 lesions (2914 naevi, 130 lentigos, 151 melanomas, 51 dysplastic naevi, 21 Hutchinson's melanotic freckles and eight other melanocytic lesions) were analysed. Twenty-one per cent of the treatment sessions involved the excision of more than one lesion; 5% involved three lesions or more. Most lesions were managed by one doctor. The overall mean margin of excision was 2.8 mm. It was greater for longer qualified doctors, surgeons and college-affiliated general practitioners, for lesions excised to address malignancy (3.0 mm) rather than cosmetic appearance (2.4 mm), for Hutchinson's melanotic freckles (5.9 mm) and melanomas (5.1 mm) compared with benign lesions (2.7 mm) (P < 0.001) and for older patients (2.6 mm for those < or = 15, 3.5 mm for those > 40 years) (P = 0.001). Wider excisions of skin melanocytic lesions are performed by older and more experienced doctors, on older patients, and for lesions in which malignancy is being addressed.     

Effect of high-dose oral ganciclovir on didanosine disposition in human immunodeficiency virus (HIV)-positive patients

This study was designed to investigate the interaction between high-dose oral ganciclovir (6,000 mg/day) and didanosine at steady state in patients who were seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) infection. The study was conducted as an open-label, randomized, three-period crossover study. Patients received (in random order) multiple oral doses of didanosine 200 mg every 12 hours alone, ganciclovir 2,000 mg every 8 hours alone, and ganciclovir 2,000 mg every 8 hours in combination with didanosine 200 mg every 12 hours. Blood and urine samples for determinations of drug concentrations were obtained on day 3 of each dose regimen. When ganciclovir was administered either before or 2 hours after didanosine, the mean increases in maximum concentration (Cmax), area under the concentration-time curve (AUC0-12), and percent excreted in urine of didanosine were 58.6% and 87.3%, 87.3% and 124%, and 100% and 153%, respectively. There were no statistically significant effects of didanosine on the steady-state pharmacokinetics of ganciclovir in the presence of didanosine, irrespective of sequence of administration. There were no significant changes in renal clearance of didanosine, suggesting that the mechanism for the interaction does not involve competition for active renal tubular secretion. The mechanism responsible for increased didanosine concentrations and percent excreted in urine during concurrent ganciclovir therapy may be a result of increased bioavailability of didanosine. However, the mechanism appears to be saturated at oral ganciclovir doses of 3 g/day.     

Effect of food on the bioavailability of stavudine in subjects with human immunodeficiency virus infection

A randomized, three-way crossover study was carried out to determine the effects of food ingestion on the pharmacokinetics of stavudine (d4T). Fifteen subjects with human immunodeficiency virus (HIV) infection and CD4(+) cell counts of >/=200/microliter received 70 mg of d4T in a fasting state or 1 h before or 5 min after a standardized high-fat breakfast. A 7- to 15-day washout period was included between treatments. Blood and urine were collected before and for 10 h after dosing, and plasma and urine d4T concentrations were determined with a validated radioimmunoassay. Plasma drug concentration-time data were analyzed with a noncompartmental model. The mean maximum plasma drug concentration (Cmax) and the time to Cmax (Tmax) for administration of d4T after a meal were significantly lower and longer (P = 0.0001 for both measures) than those observed in the fasting state, although the area under the concentration-time curve from time zero to infinity (AUC0-infinity) was not significantly different. Neither of these parameters was significantly altered when d4T was taken 1 h before a meal. The bioavailability of d4T taken after a meal was 95% of that observed in the fasting state, and it was 97% when d4T was administered before a meal (P > 0.05 for both comparisons with the fasting state). The results of this study indicate that (i) ingestion of food does not affect the bioavailability of d4T and that patients with HIV infection can take it without regard to meals, and (ii) absorption is essentially complete within 1 h when d4T is administered in the fasted state.     

Orthopaedic surgery in hemophilic patients with human immunodeficiency virus

Patients registered at the author's hemophilia center between 1982 and 1994 were studied to establish whether major orthopaedic surgical procedures accelerate the fall of CD4 lymphocyte counts of patients with hemophilia who are infected with the human immunodeficiency virus, and whether patients who had surgery had different rates of development of acquired immune deficiency syndrome or death when compared with patients who did not have surgery. The patients were divided into four groups: Group 1, 22 patients who were human immunodeficiency virus positive undergoing orthopaedic surgery; Group 2, 89 patients who were human immunodeficiency virus positive not undergoing orthopaedic surgery; Group 3, 18 patients who were human immunodeficiency virus negative undergoing orthopaedic surgery; and Group 4, 135 patients who were human immunodeficiency virus negative not undergoing orthopaedic surgery. There was no significant difference between the rates of decline of CD4 lymphocyte counts for patients who were human immunodeficiency virus positive who underwent surgery when compared with human immunodeficiency virus positive patients who did not undergo surgery, nor was there any significant difference between the two human immunodeficiency virus negative groups. There were no significant differences in the rate of development of acquired immune deficiency syndrome or mortality rates between patients who had surgery and those who did not.     

Musculoskeletal infections in patients with human immunodeficiency virus infection

Musculoskeletal infections constitute an unusual clinical manifestation in patients with human immunodeficiency virus (HIV) infection. Available information about patients' characteristics and their clinical course has been obtained mainly from case reports and small retrospective studies. Our retrospective study is the largest in the literature providing detailed information about the clinical and laboratory characteristics of HIV-infected patients with different musculoskeletal infections. We identified 30 patients with various infections of the musculoskeletal system during a 5-year period among a cohort of 3,000-4,000 HIV-infected patients, and we describe them along with all cases of musculoskeletal infections in patients with HIV reported in the literature since 1985. Septic arthritis was the most commonly reported infection of the musculoskeletal system. It usually affects young men with a median CD4 count of 241. The exact contribution of a previous history of intravenous drug abuse in the pathogenesis of septic arthritis is unclear from the present and previous studies. Staphylococcus aureus was the most commonly isolated agent (31.3%). Numerous atypical pathogens were also identified as causes of septic arthritis. Approximately 90% of patients recovered with appropriate antibiotic treatment. Osteomyelitis was a more serious infection which also affected young individuals but with lower CD4 counts (median, 41). Half the cases were due to atypical mycobacteria. The mortality rate in the previously reported cases and in our series was high (20%). Pyomyositis is an increasingly recognized infection of the striated muscles in HIV-infected patients. It affects almost exclusively males with advanced HIV infection (median CD4 count, 24). Most cases are due to Staphylococcus aureus (67%). Drainage of the involved muscle(s) accompanied by proper antibiotic treatment resulted in resolution of the infection in the majority of patients (90%). Although the incidence of musculoskeletal infections in patients with HIV from this and previous studies appears to be low (0.3%-3.5%), these infections add a significant morbidity and mortality in the affected individuals. Better understanding of their pathogenesis and clinical course would aid the proper diagnosis and management of these infections.     

Drug interactions in patients infected with human immunodeficiency virus

Patients with AIDS who are receiving optimal medical care, including combination therapy with antiretroviral agents and more effective prophylaxis and therapy for opportunistic infections and neoplasms, are surviving longer. However, the potential for drug interactions in these patients is increased because many of the currently used antibiotics and antiviral agents have profound effects on the hepatic cytochrome P-450 enzyme system, on renal tubular function, and on bone marrow function. In this AIDS Commentary, Dr. Piscitelli and colleagues have succinctly reviewed the current state of our knowledge regarding the potential for additive or synergistic drug interactions that can result in enhanced toxicity or, alternatively, augmented therapeutic benefit. Information on these interactions will become more important as more intensive and effective therapy becomes available for persons with far-advanced infection due to human immunodeficiency virus type 1.     

Incidence of enteropathogens in patients with human immunodeficiency virus infection

BACKGROUND: To establish the incidence of diarrhea and its evolution over time, the causal microorganisms, recurrence and associated mortality in patients with AIDS or severe immunologic alterations (CD4 lymphocytes lower than 0.5 x 10(9)/l). METHODS: A prospective longitudinal study was carried out from 1984 to 1992. The following patients were included in the study: 1) all those patients with diarrhea in whom a pathogenic microorganism was identified in the stools, and 2) patients with fever and positive blood cultures for enteropathogenic bacteria. The patients belonged to a series of 1,456 patients with infection by HIV. RESULTS: Of the 1,456 controlled patients, 253 (17%) had infection by enteropathogenic microorganisms. The incidence was greater in homosexual patients (26%) than in drug addicts (12%). The most frequent germs were Cryptosporidium, in 104 episodes and Salmonella sp. in 78 episodes (31 as isolated bacteria). The mortality in the 15 days following isolation was 2%, the referred microorganisms being the most frequent responsible for the deaths. The mean of CD4 lymphocytes in the patients with enteropathogens was 0.17 x 10(9)/l). SD 0.14 x 10(9)/l). In patients with infection by Cryptosporidium the CD4 lymphocyte count was lower than that observed in the cases of infection by Isospora belli. Prior to 1988, 21% of the patients had infection by enteropathogenic bacteria and 23% by parasites, those percentages being 3% and 6%, respectively in 1991. CONCLUSIONS: Infections by enteropathogenic microorganisms in patients with infection by the human immunodeficiency virus in an advanced stage are frequent, particularly, in homosexuals. The patients with enteritis by Cryptosporidium have a greater grade of immunosuppression (CD4 lymphocytes lower than 0.1 x 10(9)/l) than patients with infection by other enteropathogenic microorganisms. In the last few years, the incidence of enteropathogenic bacteria, especially Salmonella sp. and protozoa has decreased [corrected].     

Pleural effusion in patients infected with the human immunodeficiency virus

In order to analyze the etiology, cytological and biochemical characteristics, and outcome of pleural disease in patients infected with HIV, the medical records of 86 HIV-positive patients with pleural effusion were reviewed. Controls were 106 HIV-negative patients with parapneumonic or tuberculous effusion. Most HIV-positive patients were intravenous drug abusers (95.3%). Pleural effusions in HIV-positive patients were caused by infections in 76 (89.4%) cases. Parapneumonic effusion was diagnosed in 59 patients and tuberculous pleuritis in 15 patients. Staphylococcus aureus was the most frequently isolated bacteria. Parameters for differentiating complicated cases of parapneumonic exudate from uncomplicated cases, such as pleural fluid pH < 7.20 (sensitivity 80% vs. 84.3%), pleural fluid glucose < 35 mg/dl (sensitivity 45% vs. 56.25%) pleural fluid LDH > 1600 UI/l (sensitivity 85% vs. 62.50%), showed similar sensitivity in HIV-positive and HIV-negative patients. Monocytes in pleural fluid were significantly decreased in tuberculous pleuritis in HIV-positive patients (506 +/- 425 vs. 1014 +/- 1196 monocytes/ml, p < 0.05). No significant differences were detected in the outcome of HIV-positive and HIV-negative patients with pleural disease. It can be concluded that the pleural effusion was of predominantly infectious etiology in HIV-positive patients from populations with a high prevalence of intravenous drug abuse. Neither the biochemical parameters in pleural fluid nor the outcome differed significantly between HIV-positive and HIV-negative patients.     

Body composition changes in patients with human immunodeficiency virus infection

Malnutrition characterized by weight loss and often extreme wasting generally develops when patients progress from infection with human immunodeficiency virus (HIV) to AIDS. There is evidence that before the development of AIDS, HIV-infected patients without weight loss show early signs of malnutrition, defined as an increase in the ratio of extracellular mass (ECM) to body cell mass (BCM). As part of a dietary intervention study, body composition measurement were obtained at baseline and after 6 wk in 18 patients with HIV infection and CD4 counts between 140 and 740 cells/mm3. Only one patient had a prior weight loss (3.7 kg); patients gained 2 pounds after 3 wk of dietary supplementation of 500 kcal daily. Bioelectrical impedance was used to measured body compartments. The average ECM/BCM ratio (0.77 +/- 0.13) was within the normal range (0.83 +/- 0.16) indicating the absence of malnutrition by this criterion. Most measurements of BCM (kg) approximated normal values, while several for BCM (kg) exceeded normal. BCM (kg) correlated poorly with the ECM/BCM ratio (r2 = 0.08; P = 0.11) in contrast to ECM (kg), which was well correlated (r2 = 0.82; P = 0.00). In addition, there was a significant correlation of body mass index (BMI) with the ECM/BCM ratio (r2 = 0.38; P = 0.00) and with ECM (r2 = 0.244; P = 0.003) indicating that overweight patients may be more likely to be considered malnourished than normal weight patients using this ratio. Without use of bioelectrical impedance, these subtle changes might be missed. Once significant weight loss has occurred coupled with decreases in BCM (kg), the ECM/BCM ratio may be more reflective of malnutrition. These conjectures will require prospective evaluation, but for now it seems reasonable to include bioelectrical impedance as a potentially useful tool in the evaluation of malnutrition in this population.     

Refractory mucosal candidiasis in patients with human immunodeficiency virus infection

Difficult-to-manage mucosal candidal infection has been a hallmark of individuals with advanced infection due to human immunodeficiency virus type 1. In this AIDS Commentary, Drs. Fichtenbaum and Powderly comprehensively review the literature and their experience with refractory candidiasis in such patients. Of interest is their delineation of resistance, a lack of susceptibility to an antifungal agent in vitro among patients with refractory or clinically unresponsive disease. These authors believe that the establishment of resistance should be based upon standards established by the National Committee on Clinical Laboratory Standards, which they propose to define as a failure to respond to systematic therapy with specific doses of itraconazole, fluconazole, or parenterally or orally administered amphotericin B within 14 days. There have been many definitions of "refractory candidiasis," and the one proposed by these authors will be debated; however, this definition has the advantage of establishing a standard by which to judge the efficacy of their proposed algorithm for the treatment of persistent or refractory oropharyngeal candidal infections. Drs. Fichtenbaum and Powderly have performed a useful service in their attempt to bring coherence to the management of this common and often vexing problem.     

Cavitary pulmonary lesions in patients infected with human immunodeficiency virus

The differential diagnosis of cavitary pulmonary lesions in individuals infected with human immunodeficiency virus (HIV) is broad, especially in patients with advanced disease. In patients with Pneumocystis carinii pneumonia, cavitation is an uncommon manifestation of a common disease. It is unusual in patients with pulmonary cryptococcosis, coccidioidomycosis, and histoplasmosis but occurs frequently in patients with invasive pulmonary aspergillosis. In patients with pulmonary tuberculosis, cavities are more common during earlier stages of HIV disease, when cellular immunity is relatively preserved. Mycobacterium avium complex is an uncommon cause of lung disease and infrequently produces cavities. However, Mycobacterium kansasii, is often associated with cavitation. Cavities can complicate any bacterial pneumonia and are especially common with pneumonia due to Pseudomonas aeruginosa, Nocardia asteroides, and Rhodococcus equi. Noninfectious causes of cavitary lesions are rare, but cavitary lesions caused by pulmonary Kaposi's sarcoma and non-Hodgkin's lymphoma have been reported. Because of the broad differential diagnosis and because most cavities are caused by treatable opportunistic infections, a definitive diagnosis is essential.     

A comparison of 2 weeks of terbinafine 250 mg/day with 4 weeks of itraconazole 100 mg/day in plantar-type tinea pedis

This double-blind, parallel group study compared a 2-week course of terbinafine 250 mg/day with a 4-week course of itraconazole 100 mg/day. A total of 190 patients were enrolled, of whom 129 were evaluable for efficacy. At week 8, 69% of patients treated with terbinafine were classified as effectively treated (mycological cure, and clinical assessment total score < or = 2) vs. 67% in the itraconazole group. At week 16, however, the rating for effective treatment increased to 71% of the terbinafine group, but decreased to 55% of the itraconazole group. This difference was of borderline statistical significance (P = 0.06). The results of this study demonstrate that both drugs can be used safely, and that 2 weeks' treatment with terbinafine 250 mg daily is as effective as 4 weeks' treatment with itraconazole 100 mg daily, but with fewer long-term relapses.     

Thrombocytopenia in patients infected with human immunodeficiency virus: treatment update

Thrombocytopenia that is associated with infection due to human immunodeficiency virus (HIV) is an important and common hematologic abnormality. Although this condition is often asymptomatic, it may manifest clinically as a spectrum of bleeding problems including petechiae, ecchymoses, epistaxis, or menorrhagia or as hemorrhage of the gingivae, gastrointestinal tract, or CNS. Thrombocytopenia may be present in patients at any stage of immunodeficiency, and spontaneous remission can occur. We review the natural history of HIV-related thrombocytopenia and discuss treatment options.     

Adverse reactions to thalidomide in patients infected with human immunodeficiency virus

Thalidomide is emerging as a useful agent in the management of several complications of disease due to human immunodeficiency virus (HIV). We conducted three prospective studies of 56 HIV-infected patients who were treated with thalidomide for 14-21 days; 24 (43%) of these patients discontinued therapy owing to adverse reactions. Cutaneous and/or febrile reactions were the most frequent toxicities, arising in 20 (36%) of the patients. These reactions occurred after a mean interval (+/-SD) of 10 +/- 3 days and were associated with significantly lower CD4 T lymphocyte counts in reactors than in nonreactors (median count, 52.5/mm3 vs. 242 cells/mm3, respectively; P = .009). Four of four rechallenged patients experienced accelerated hypersensitivity; hypotension occurred in one case. Although sedation was an almost universal side effect among the patients, it was moderate or severe in only seven (13%); constipation was moderate or severe in five (9%) of the patients. Severe neuropathic symptoms and mood changes were each noted in two (4%) of the 56 patients. We conclude that the increasing use of thalidomide to treat HIV-infected patients must be accompanied by recognition of the drug's increased potential for toxicity in this population.     

Pulmonary toxoplasmosis in patients with human immunodeficiency virus infection. 21 cases

OBJECTIVES: Assess expression of pulmonary toxoplasmosis, the second most frequent localization after brain, in patients infected with the human immunodeficiency virus (HIV). METHODS: Twenty-one HIV-infected patients (18M, 3F) were admitted for pulmonary toxoplasmosis between September 1987 and February 1995. Mode of HIV transmission was unprotected homosexual sexual activity (n = 16), intravenous drug abuse (n = 3) and transfusion (n = 2). RESULTS: Isolated pulmonary toxoplasmosis was found in 11 patients. In 10 patients pulmonary toxoplasmosis was associated with cerebral (n = 4), bone marrow (n = 2), ocular (n = 1) and multifocal (n = 3) localizations. Seven patients were admitted for acute pulmonary distress. Fever (reported for 20 patients) and nonproductive cough (reported for 16 patients) were the most common clinical symptoms. Chest roentgenogram revealed bilateral pulmonary infiltrates in 16 (76%) patients. Mean absolute CD4 count was 25 +/- 57 (range 0-110). Serologic evidence of past infection was observed in 18 patients. Serology tests were not done for two patients and negative for one. Two patients presented co-infection with Pneumocystis carinii. Fourteen patients had elevated serum lactic dehydrogenase (LDH) concentration. Among those, 4 patients whose LDH concentration was elevated more than ten fold died of respiratory distress. Patients received pyrimethamine and sulfadiazine (n = 13) or clindamycin (n = 8). Seven patients died during the first month after diagnosis was made. For the other patients, mean survival was 8 months. No relapse of toxoplasmosis was observed. All the patients took a secondary prophylaxis. CONCLUSION: No difference between patient with isolated pulmonary toxoplasmosis and patients with associated extra-pulmonary localization was noted for clinical, biological, radiological presentations and outcome.