David Feigal

The prevalence of oral lesions in HIV-infected homosexual and bisexual men : three San Francisco epidemiological cohorts

To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposis sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CD 17.5–23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% Cl 4.1–7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposis sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P < 0.05). The prevalence of erythematous candidiasis and Kaposis sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.

Treatment of Toxoplasmic Encephalitis in Patients with AIDS: A Randomized Trial Comparing Pyrimethamine plus Clindamycin to Pyrimethamine plus Sulfadiazine

OBJECTIVE To compare pyrimethamine plus clindamycin (PC) to pyrimethamine plus sulfadiazine (PS) as a treatment for toxoplasmic encephalitis (TE) in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Randomized, unblinded phase II, multicenter trial with provision for crossover for failure or intolerance of the assigned regimen. SETTING University hospitals. PATIENTS Eighty-four patients with presumptive TE were entered. Thirteen were excluded when they were found to have another diagnosis, and 12 were excluded because they did not meet entry criteria. The baseline characteristics in the remaining 26 patients randomized to PC and 33 randomized to PS were comparable. INTERVENTIONS Patients were treated for 6 weeks with pyrimethamine and folinic acid plus either sulfadiazine or clindamycin. Clindamycin was given intravenously during the first 3 weeks. MEASUREMENTS AND MAIN RESULTS There was a trend toward greater survival in patients randomized to PS (hazard ratio, 3.25; 95% CI, 0.63 to 16.8; P = 0.13), but most study deaths were not directly related to TE. In contrast, patients randomized to PC appeared more likely to achieve complete clinical (odds ratio, 0.67; CI, 0.2 to 1.97; P greater than 0.2) and radiologic responses (odds ratio, 0.28; CI, 0.08 to 0.96; P = 0.02). Multivariate analysis revealed drug effects to be largely independent of other variables. Similar efficacy of the treatments was also suggested by a hazard analysis of resolution of abnormal mental status, fever, and headache. Skin rash was the most common adverse event in both treatment arms. Because of toxicity, six patients randomized to PC and 11 patients randomized to PS had to switch to the alternate treatment, but only three were unable to complete therapy after crossover. CONCLUSIONS The results of several end points of efficacy, taken together, suggest that the relative efficacy of PC approximately equals that of PS. PC appears to be an acceptable alternative in patients unable to tolerate PS.

Hypernatremia in Elderly Patients: A Heterogeneous, Morbid, and Iatrogenic Entity

The causes, therapy for, and consequences of hypernatremia in elderly patients are not well understood. We found that in 15,187 consecutive hospital admissions, 162 (1.1%) patients who were at least 60 years of age had serum sodium levels that measured greater than 148 meq/L. Of that 162, 57% had become hypernatremic in the hospital; the remaining 43% were hypernatremic at hospitalization. The mean peak serum sodium level was 154 meq/L (range, 149 to 182), and mean water deficit, 9% of total body water (range, 6% to 30%). The most frequent primary causes were complications of surgery (21%), febrile illness (20%), infirmity (11%), and diabetes mellitus (11%), with more than 40 causal factors identified. Depression of sensorium correlated with severity of hypernatremia (p less than 0.001). The mortality rate (42%) was seven times that of age-matched hospitalized patients, but was not predicted by severity of hypernatremia. Mortality increased with increasing rates of fluid replacement (p less than 0.008). Hypernatremia in elderly patients is usually iatrogenic and often a marker for severe associated systemic illness.

Estrogen replacement therapy and the risk of venous thrombosis

PURPOSE Estrogen replacement therapy is believed by many physicians to cause thrombophlebitis and to be contraindicated in women at risk for this disease. However, clinical data supporting this assumption are scant, and further investigation is required. PATIENTS AND METHODS We tested the estrogen-thrombophlebitis association in a case-control study. Charts of all consecutive women aged 45 years or older with a primary or secondary discharge diagnosis of thrombophlebitis, venous thrombosis, or pulmonary embolism were reviewed; 121 cases and 236 controls matched for age, year of admission, admitting service, and socioeconomic status were obtained. Hormone use and nonuse were validated in a subset of randomly selected women. RESULTS Cases and controls, whose average age was 65 years, did not differ significantly on matching variables or on current use of exogenous estrogen (5.1% of cases versus 6.3% of controls). Other analyses that variously excluded women with a past history of thrombosis, women less than 50 years of age, women with thrombosis occurring after admission, and women whose estrogen use was indeterminate also did not support an increased risk of thrombotic disease. Adjustment for the presence of independent thrombotic risk factors did not alter the odds ratio for estrogen use. CONCLUSION This case-control study of older women, unselected for other thrombotic risk factors, does not support the commonly held assumption that replacement estrogen increases the risk of venous thrombosis.

Progression to AIDS in HIV-infected homosexual and bisexual men with hairy leukoplakia and oral candidiasis.

ObjectiveThis study was designed to assess the significance of HIV-related oral lesions in predicting the rate of progression to AIDS. DesignCohorts were investigated prospectively, and oral examinations were performed by clinicians trained in the diagnosis of oral lesions.Setting: We studied three existing cohorts of homosexual and bisexual men in San Francisco, California, USA. ParticipantsOf the HIV-infected men who received standardized oral examinations (n = 791), 603 were eligible for analysis of baseline examinations and 448 for analysis of follow-up examinations. Main outcome measuresWe determined time from presence of oral lesion at baseline or follow-up examination, or from participant self-reported history of the lesion, to diagnosis of AIDS. ResultsUsing proportional hazard regression and stratifying by CD4 lymphocyte count at the time of baseline oral examination, we found that the rate of development of AIDS was increased among men with hairy leukoplakia [relative hazard, 1.8; 95% confidence interval (CD, 1.2–2.7], oral candidiasis (relative hazard, 7.3; 95% CI, 3.1–17.3), and both lesions (relative hazard, 3.1; 95% CI, 1.6–6.1) compared with men with normal findings. On follow-up examination, stratifying for CD4 count, the rate of progression to AIDS was similar for those with hairy leukoplakia compared with those with oral candidiasis. The progression rate from oral candidiasis to AIDS was faster from presence on baseline examination than from presence on follow-up examination or from self-reported history of the lesion. ConclusionThe presence of oral candidiasis and/or hairy leukoplakia on baseline examination confers independent prognostic information and should be incorporated into HIV-staging schemes.

Oral candidiasis in HIV infection: pseudomembranous and erythematous candidiasis show similar rates of progression to AIDS.

Candidiasis is the most common oral fungal infection seen in association with HIV infection. It may present in a number of clinical forms, including pseudomembranous and erythematous candidiasis. To determine whether erythematous candidiasis, like the pseudomembranous form, is predictive of the development of AIDS, we reviewed the records of 169 HIV-seropositive patients seen at clinic of the Oral AIDS Center, University of California, San Francisco who were diagnosed with pseudomembranous or erythematous (or both) forms of oral candidiasis at their first examination. Kaplan-Meier analysis showed a rapid rate of progression to AIDS (median, 25 months) and to death (median, 43.8 months) in all three groups. We conclude that erythematous candidiasis is as serious a prognostic indicator as pseudomembranous candidiasis. Because the erythematous form is more difficult to recognize and hence is underdiagnosed, efforts should be made to teach non-dental clinicians who care for HIV-infected patients to diagnose and treat this lesion.

PREVENTION OF PNEUMOCYSTIS CARINII PNEUMONIA BY INHALED PENTAMIDINE

The efficacy and toxicity of pentamidine inhaled once a month to prevent Pneumocystis carinii pneumonia (PCP) was investigated in 102 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). The cohort was compared with historical controls after a mean duration of prophylaxis of 6.38 months. 86% and 15% of the patients had AIDS or ARC, respectively. 50% of patients had had one previous episode of PCP, 9% had had two episodes, and 3% had had three. 11 patients acquired PCP. Among these 51 patients with one prior episode of PCP, the PCP-free survival after 3.03, 4.7, and 6.38 months of prophylaxis was 98%, 92%, and 82%, respectively. Compared with those for historical controls, the data suggest that inhaled pentamidine can delay relapse by 6 months and reduce the rate of relapse by 50%. PCP acquired while patients were inhaling pentamidine prophylactically was mild and had a case-fatality rate of only 9%. Further investigation of the prophylactic value of inhaled pentamidine is warranted.

Systolic hypertension in the elderly program (SHEP): the first three months

T he Systolic Hypertension in the Elderly Program (SHEP) addresses the question: Should elderly patients with isolated systolic hypertension (ISH) receive antihypertensive drug treatment? The population we are concerned with is men and women age 60 years and older who consistently have a systolic blood pressure exceeding 160 mmHg and a diastolic blood pressure less than 90 mmHg. The goal of this report is to present the findings from the first three months of a study to demonstrate the feasibility of a full-scale randomized clinical trial. Specifically, we will address the issues of recruitment, compliance, treatment efficacy, and adverse effects.

Recurrent aphthous ulcers in association with HIV infection: Description of ulcer types and analysis of T-lymphocyte subsets

This study was conducted to characterize the recurrent aphthous ulcers (RAU) found in association with human immunodeficiency virus (HIV) infection, to examine evidence for increased severity of the ulcers with HIV disease, and to determine whether increased severity is associated with abnormalities of peripheral blood lymphocyte subsets. Seventy-five HIV-seropositive patients with RAU were followed for up to 2 years, and lymphocyte subsets were analyzed in 42. Minor, herpetiform, and major ulcer types were seen, but unexpectedly, 66% of the patients had the usually uncommon herpetiform and major types. These types were temporally associated with symptomatic HIV disease. Patients with major RAU were significantly more immunosuppressed than those with minor or herpetiform RAU in that they had fewer CD4 and CD8 lymphocytes (p less than 0.05). The lesion of RAU is considered to represent a local breakdown in immunoregulation. The systemic immune imbalance seen with HIV disease may amplify the local defect and lead to more severe ulcers.

Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS: a randomized trial.

OBJECTIVE To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. INTERVENTIONS Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. MEASUREMENTS AND MAIN RESULTS The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. CONCLUSIONS The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma.