Biomedical subjects
Publications and source records attributed to D W Feigal.
Explore the source record for details and available documents.
Pneumocystis carinii pneumonia remains one of the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS). Treatment with either intravenous pentamidine or trimethoprim-sulfamethoxazole (TMP-SMX) is frequently complicated by serious adverse reactions. This study was a prospective, blinded comparison of 600 mg/d of pentamidine as an aerosol versus 15 mg/kg/d of trimethoprim plus 75 mg/kg/d of sulfamethoxazole for patients with mild or moderately severe P. carinii pneumonia (alveolar arterial oxygen difference of less than 55 mm Hg). Of 367 participants who were randomized to receive study therapies, 287 had proven and 16 had presumed Pneumocystis pneumonia. There were 29 deaths within 35 d of study initiation: 12 in the aerosolized pentamidine group and 17 in the TMP-SMX groups (log rank p = 0.28). The difference in mortality was 3.4% (95% CI = -3.5, 10.8%). Ninety-four patients treated with aerosolized pentamidine had to have their study therapy changed because of lack of efficacy, compared with 22 patients treated with TMP-SMX (p = 0.002). In addition PaO2 improved faster in patients treated with TMP-SMX. However, aerosolized pentamidine was discontinued less often than TMP-SMX because of toxicity (9.4 versus 40% p < 0.001). Rash (0.6 versus 14.9%), nausea and vomiting (1.7 versus 12.2%), and abnormalities of liver function tests (1.7 versus 12.2%) were the most common adverse effects necessitating treatment discontinuation. During 6-mo. follow-up there was no difference in mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To learn about the status of junior faculty in the specialty of pulmonary diseases and about their attitudes concerning their future in academic medicine. DESIGN: Mailed survey. PARTICIPANTS: A total of 209 junior pulmonary faculty were reported by the directors of the 106 US pulmonary training institutions with at least 3 fellow training positions; 157 (75 percent) responded to our questionnaire. RESULTS: Most respondents described themselves as happy and productive, and almost all planned to stay in academic medicine. However, some problems were evident that could interfere with their plans to remain: a lack of protected time for research (only 15 percent of assistant professors and instructors spent 75 percent or more of their time in research), a lack of understanding about the rules and procedures of promotion (only 31 percent said they understood), failure of communication with the Chiefs of the Division and of Medicine (less than half had had a meeting about promotion with the Chief of the Division, 16 percent with the Chairman of Medicine), and a concern about their financial security (73 percent were concerned). Although women, who represented only 13 percent of the respondents, reported similar work hours and publication rates, they were less optimistic about promotion than the men (40 percent of women considered their chance for promotion good to excellent vs 64 percent of men). The junior faculty reported that the greatest obstacles to their academic success were insufficient protected time for their research, maintaining research productivity, and inadequate and uncertain funding. CONCLUSIONS: The success of junior faculty is important to the success of academic medicine. More attention should be paid to ensuring protected continuous time for research, educating about promotion, and improving funding opportunities.
OBJECTIVE: To determine the reliability and validity of various physical diagnostic techniques (including three methods of palpation and three methods of percussion) in detecting ultrasonographically identified splenomegaly. DESIGN: Prospective, double-blind study. SETTING: University hospital. PATIENTS: Twenty-seven hospitalized male patients with suspected human immunodeficiency virus (HIV) infection. INTERVENTIONS: Three methods of palpation (bimanual, ballottement, and palpation from above) and three methods of percussion (as described by Nixon, Castell, and Barkun et al.) were performed on each patient by eight examiners. Splenic ultrasonography was performed within 96 hours of admission. MEASUREMENTS AND MAIN RESULTS: The prevalence of splenomegaly by ultrasonography (defined as a spleen > or = 13 cm on the longitudinal scan) in this population was 33.3%. The sensitivity and specificity of each method of palpation and percussion varied by examiner. The ranges of sensitivity across examiners for the three methods of palpation and the three methods of percussion were 0%-64.3% and 7.7%-75%, respectively. The ranges of specificity across examiners for the three methods of palpation and the three methods of percussion were 50%-100% and 60%-100%, respectively. Likelihood ratios pooled across observers revealed that for palpation, palpation from above, and percussion, Castell's method had the highest likelihood ratios [LR = 2.66 and 1.97, respectively; 95% CI = 1.52-4.64 and 1.22-3.19, respectively]. A combination of tests (either palpation or percussion) increased the diagnostic accuracy. CONCLUSION: Physical diagnostic techniques for the detection of splenomegaly are relatively insensitive but specific. In this study there was high interobserver variability, which did not appear to be associated to the level of experience. Combining tests increases diagnostic accuracy.
Explore the source record for details and available documents.
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.
This study sought to better characterize the natural history of AIDS-associated disseminated Mycobacterium avium complex (MAC) infection. Towards that end two retrospective studies were done: a case-control survival study and a MAC respiratory colonization study. Among 137 consecutive patients who had a sterile body site cultured for mycobacteria within 3 months of their first AIDS-defining episode of Pneumocystis carinii pneumonia, median survival was significantly shorter in those with disseminated MAC infection (107 days; 95% confidence interval [CI] 55-179) than those with negative cultures (275 days; 95% CI 230-318; P less than .01), even after controlling for age, absolute lymphocyte count, and hemoglobin concentration. Among 34 patients with AIDS and respiratory MAC colonization, 22 later developed disseminated infection (65% predictive value for subsequent MAC dissemination). Disseminated MAC infection was associated with significantly shorter survival for patients with AIDS, and the presence of MAC in respiratory specimens has substantial predictive value for subsequent disseminated infection.
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, Kaposi's 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 (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status.
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.
To determine risk factors for early progression from oral hairy leukoplakia to AIDS, this case-control study compared 27 patients who had not progressed to AIDS within 1,000 days of diagnosis of hairy leukoplakia with 28 patients who progressed rapidly. The risk factors that proved most predictive fell into two categories: (a) those reflecting sexual practices that correlated with how early in the epidemic patients were likely to have been infected, and (b) those reflecting immune competence. Hepatitis B was associated with a fourfold risk for early progression and syphilis with a nearly threefold risk. Skin test anergy for Candida species was strikingly predictive: all of 17 tested in the early progression group were anergic, compared with only two of 12 tested in the late progression group. Although skin testing has been largely supplanted by assessment of T-cell subsets, Candida species skin testing may be of particular prognostic value in otherwise apparently healthy HIV-infected persons.
BACKGROUND AND METHODS: Pneumocystis carinii pneumonia (PCP) is the most frequent life-threatening opportunistic infection associated with human immunodeficiency virus (HIV) infection. To assess the possible value of aerosolized-pentamidine prophylaxis in different doses, a controlled clinical trial was begun in 1987 with 408 subjects at 12 treatment centers. The participants were randomly assigned to receive 30 mg of pentamidine every two weeks, 150 mg every two weeks, or 300 mg every four weeks. RESULTS: Eighteen months after randomization, the subjects in the 300-mg arm had had 8 confirmed episodes of PCP while receiving treatment, as compared with 22 in the 30-mg arm (P = 0.0008). The 150-mg arm had intermediate results but ones not significantly different from those of the 300-mg arm. Participants with previous episodes of PCP and CD4-cell counts less than 200 per cubic millimeter were at the highest risk for PCP. CONCLUSIONS: Aerosolized pentamidine was effective for prophylaxis against PCP in patients infected with HIV, according to the dose and schedule of administration. It and zidovudine were well tolerated together and had independent prophylactic benefits.
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.
To develop a model for predicting acquired immunodeficiency syndrome (AIDS) morbidity in San Francisco, Calif, through June 1993, we combined annual human immunodeficiency virus seroconversion rates for homosexual and bisexual men and for heterosexual intravenous drug users with estimates of the cumulative proportion of the population with AIDS by duration of human immunodeficiency virus infection and with estimates of the size of the at-risk populations. We projected AIDS mortality by applying Kaplan-Meier estimates of survival time following diagnosis to the projected number of cases. The median incubation period for AIDS among homosexual and bisexual men infected with the human immunodeficiency virus was estimated to be 11.0 years (mean, 11.8 years; 95% confidence interval, 10.6 to 13.0 years). The model projects 12,349 to 17,022 cumulative cases of AIDS in San Francisco through June 1993, with 9,966 to 12,767 cumulative deaths.
Explore the source record for details and available documents.
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.
Men and women with isolated systolic hypertension who were at least 60 years of age were treated for 1 year with chlorthalidone (25-50 mg daily) or matching placebo as the step I drug. Most patients reached goal blood pressure without requiring a step II drug. The blood pressure response was similar in all age, sex and race subgroups, with an overall difference between the randomised groups of 17 mm Hg for systolic blood pressure (p less than 0.001) and 6mm Hg for diastolic blood pressure (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum concentrations of potassium (0.5 mmol/L lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001), and creatinine (0.08 mg/dl higher, p = 0.02). Compliance was good, and more than 80% of participants were still taking the study medications at the end of the year.
Rheumatoid factors (RF) constitute the major autoantibodies in rheumatoid arthritis (RA). RF are directed against IgG Fc, are polyclonal, and are predominantly of the IgG and IgM classes. RF may participate in both synovial and extraarticular inflammation in RA, although the precise roles of serum IgG and IgM RF are unclear. The purpose of our study was to correlate serum IgG RF with serum IgM RF levels measured by radioimmunoassay and with clinical disease activity in 42 prospectively evaluated seropositive RA patients. IgM RF correlated with IgG RF levels and articular disease activity. IgG RF correlated with IgM RF but not with articular disease activity when adjusted for IgM RF.
Giant cell arteritis is a necrotizing granulomatous arteritis of large arteries, especially the aorta and its branches. Mononeuritis multiplex is a peripheral sensorimotor neuropathy usually producing foot or wrist drop, commonly associated with necrotizing arteritis of small and medium-sized arteries. Rheumatoid vasculitis is an example of the latter type of arteritis associated with high-titer 19S IgM rheumatoid factor typically occurring in patients with long-standing erosive rheumatoid arthritis. This report describes a 71-year-old man with biopsy-proved giant cell arteritis, mononeuritis (foot drop) multiplex, and high-titer complement-activating rheumatoid factor without rheumatoid arthritis. Possible pathogenic relationships are discussed.