Development of histoplasmosis in a human immunodeficiency virus-infected patient receiving fluconazole.
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Biomedical subjects
Publications and source records attributed to J C Pottage.
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We retrospectively analyzed data from 75 hospitalized patients with a first episode of Pneumocystis carinii pneumonia to compare the ability of four parameters, including admission serum albumin, serum lactate dehydrogenase (LDH), alveolar-arterial oxygen gradient, and the APACHE II score, to predict mortality and response to initial antipneumocystis therapy. The eight patients who died due to pneumocystosis and the 12 who failed initial antipneumocystis therapy had significantly higher admission mean APACHE II scores and serum LDH levels and lower mean serum albumin levels than did the 65 who survived and the 61 who responded to initial therapy (p less than 0.05 for each). Differences in mean alveolar-arterial oxygen gradients were not statistically significant with respect to survival or response to initial therapy. In a stepwise discriminant analysis of parameters associated with mortality, APACHE II score and LDH level were statistically significant (p less than 0.0001 for each). In a stepwise discriminant analysis of parameters associated with response to initial therapy, APACHE II score and LDH level were again statistically significant (p less than 0.0001, respectively). The addition of the alveolar-arterial oxygen gradient and serum albumin level did not further increase the predictive ability of the discriminant analyses. When analyzed alone, neither the alveolar-arterial oxygen gradient nor the serum albumin were statistically significant in each discriminant analysis. The APACHE II score combined with the serum LDH may be more useful than other parameters, singly or combined, to more closely match patients with regard to severity of illness due to first episode Pneumocystis carinii pneumonia when comparing experimental new therapies with standard agents.
Disease due to Mycobacterium avium complex (MAC) in patients with the acquired immunodeficiency syndrome (AIDS) typically occurs late in the course of AIDS and is usually disseminated with evidence of multiorgan involvement. Most patients are persistently bacteremic. Previously published studies have noted a poor response to antimycobacterial chemotherapy. We describe successful treatment of MAC disease in an AIDS patient with a multiple drug regimen, including amikacin, clofazimine, rifampin, ethambutol, and ciprofloxacin. This patient, whose presentation and MAC disease course distinctly differ from most published experience, remains clinically and microbiologically MAC-disease free 25 months after initiation of therapy. We describe four additional AIDS patients with MAC disease who had a favorable clinical and microbiological response to this regimen without developing serious adverse effects after periods ranging from 4 to 12 months. We suggest a prospective, controlled clinical trial using this regimen for treatment of MAC disease in patients with AIDS may be warranted.
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To improve isolation of human immunodeficiency virus (HIV) from purified monocytic cell populations, a differential culture technique was applied to blood from HIV-seropositive individuals, culture-negative for HIV by routine culture. When 206 individuals were grouped by percentage of CD4+ lymphocytes, increases in viral isolation rates were significantly associated with declines in percentage of CD4+ cells (P less than .0001). Of 158 asymptomatic individuals, 78% had greater than 400 CD4+ lymphocytes/mm3. Only 19% were culture-positive using routine methods. Separation of peripheral blood mononuclear cells (PBMC) into purified lymphocyte and monocyte subpopulations for 12 asymptomatic patients and subsequent HIV culture of each purified subpopulation using three different indicator cell lines resulted in 100% virus recovery from purified monocytes cultured in the U-937 promonocytic cell line. Culture of purified lymphocytes in U-937 cells did not increase the isolation rate, whereas culture of patient PBMC in U-937 indicator cells and in allogeneic monocytes resulted in a 50% increase in HIV isolation. A monocytic indicator cell line added to routine culture methods may improve virus recovery from asymptomatic individuals.
Fifty-eight AIDS patients who previously had Pneumocystis carinii pneumonia (PCP) were enrolled in an open trial of zidovudine therapy. We analyzed baseline clinical and laboratory parameters to identify predictors of outcome. Fifty-eight patients were followed for a mean of 26.5 weeks. There were 17 deaths; the probability of survival at 24 weeks was 0.81. Forty-one participants had unsuccessful outcomes, which included new opportunistic infections (24), progressive neurologic deterioration (2), and drug toxicity, excluding anemia, necessitating discontinuation of zidovudine (15). Only 24 subjects (41%) were receiving zidovudine at the end of the study period including 17 who had neither opportunistic infection nor toxicity. Low baseline hemoglobin level (p less than 0.001) and poor performance status as measured by the Karnofsky scale (p less than 0.01) independently predicted unsuccessful outcome and early death. Low hemoglobin (p = 0.001), low platelet count (p = 0.016), and increased time since PCP (p = 0.008) predicted development of drug toxicity. Neither CD4 lymphocyte count nor p24 antigenemia correlated with outcome.
Human immunodeficiency virus (HIV)-related thrombocytopenia has been well described and requires therapy in about one half of the patients. Conventional modes of therapy with prednisone, danazol, immunoglobulin, and/or splenectomy have not been uniformly successful. We have administered zidovudine to three patients with HIV-related thrombocytopenia. All three patients responded with a sustained increase in their platelet counts, despite discontinuation of conventional therapy. Interruption of zidovudine therapy was associated with a decrease in platelet count. Concomitant with the elevation in platelet count with zidovudine therapy, there was a reduction in the circulating p24 antigen levels. Whether the elevations in the platelet count in these patients with HIV-related thrombocytopenia is due to the antiviral effect of zidovudine is unknown. It is clear that further studies examining the prospective use of zidovudine in the treatment of HIV-related thrombocytopenia are indicated.
PURPOSE: Acyclovir and high doses of intramuscular leukocyte interferon have been shown to prevent dissemination of herpes zoster in cancer patients with localized herpes zoster. With the availability of recombinant interferon, we decided to conduct a multicenter, placebo-controlled, double-blind trial of intramuscular recombinant interferon alpha-2a to assess its efficacy and safety in the treatment of localized herpes zoster in immunosuppressed patients with cancer. PATIENTS AND METHODS: Immunosuppressed cancer patients with localized herpes zoster were randomly assigned to receive placebo, 36 X 10(6) units of recombinant interferon alpha-2a per day, or 68 X 10(6) units of recombinant interferon alpha-2a per day. Due to frequent adverse effects, the 68 X 10(6) unit dose of interferon was discontinued prior to conclusion of the trial. RESULTS: Dissemination of herpes zoster occurred in 14 of the 24 patients (58 percent) who received placebo but in only four of 24 recipients (17 percent) of 36 X 10(6) units of interferon per day (p = 0.003). Adverse effects (fever, chills, headaches, gastrointestinal irritability, fatigue, and myalgias) were more common or severe in interferon-treated patients. CONCLUSION: These results suggest that interferon modifies the severity of herpes zoster in immunosuppressed patients with cancer but is associated with frequent side effects.
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Sexually transmitted diseases (STDs) are diagnosed in 10 million patients per year in the United States. The infected individuals come from all walks of life and all age groups. They may present with either genital or nongenital signs and symptoms. Most individuals are treated as outpatients, but more than a quarter of a million hospital admissions for STDs are necessary each year. These numbers will rise precipitously as the number of AIDS cases increases. More than 10,000 deaths per year are caused by STDs, primarily because of AIDS, cervical carcinoma, and hepatitis B induced cirrhosis and hepatoma. Physicians must become highly skilled in the diagnosis and treatment of the common STDs caused by herpes simplex virus, Neisseria gonorrhoeae, and Chlamydia trachomatis. Simple office microscopic skills are needed for the diagnosis of vaginitis, cervicitis, and urethritis, and all physicians should be encouraged to develop these skills. Physicians will need to keep abreast of the rapidly evolving changes in the diagnosis and treatment of STDs.
All physicians share a responsibility for educating the public in the expanding risks of sexually transmitted diseases, and in the vital importance of safe sexual practices. Both the public health implications of undiagnosed STDs and the adverse social consequences of an incorrect diagnosis emphasize the need to comprehensively and precisely diagnose these diseases, despite the problems encountered in obtaining material for culture. Current interest in AIDS should not obscure the facts that genital herpes continues to increase in prevalence, and that syphilis no longer is declining. The many extragenital syndromes associated with STDs, such as perihepatitis, polyarthritis, and acute septic states make it necessary to evaluate all sexual contacts.
The effects of suramin, an antiparasitic agent, upon in vitro hepatitis B surface antigen production by the human hepatoma cell line PLC/PRF/5 and hepatitis B virus associated DNA polymerase activity in the serum of a chronically infected patient were examined. Treatment with suramin resulted in decreases in hepatitis B surface antigen production and hepatitis B-virus associated DNA polymerase activity. The decrease in hepatitis B surface antigen production was paralleled by a general decrease in hepatoma cell viability and cellular protein synthesis. Although the inhibitory effects of suramin for hepatitis B virus appear to be nonspecific as demonstrated in these two in vitro systems, the recently announced trial of suramin for the treatment of the acquired immunodeficiency syndrome should afford an unusual opportunity to evaluate the effectiveness of suramin in the treatment of chronic hepatitis B virus infection.
The effects of ketoconazole alone and in combination with acyclovir and adenine arabinoside upon the replication of herpes simplex virus types 1 and 2 (HSV-1 and -2) were investigated by using a yield reduction assay. Ketoconazole demonstrated antiviral activity against HSV-1 and -2 and synergistic antiviral activity when it was combined with acyclovir. Combinations of ketoconazole with adenine arabinoside resulted in either interference or indifference. The effects of ketoconazole upon the protein synthesis of HSV-2-infected cells were also determined in an effort to define the mechanism of action for the antiviral activity of ketoconazole. There was no reduction of HSV proteins when compared with acyclovir. These findings suggest that further investigations of the use of ketoconazole for the treatment of HSV infections are warranted.
Haemophilus influenzae meningitis in the presence of a cerebrospinal fluid shunt has been reported uncommonly. Staphylococcus aureus and Staphylococcus epidermidis, the most common etiological agents, are usually acquired by contiguous spread from an intraoperative or perioperative source. These infections usually occur within 2 months of shunt insertion and are rarely associated with bacteremia. Review of the literature shows that infection with H. influenzae typically occurs later than with the more common pathogens, is commonly associated with bacteremia, and frequently can be treated with antibiotics alone.
An 87-year-old woman with a known atherosclerotic thoracic aneurysm died suddenly from a massive esophageal hemorrhage. Prior to death, tuberculous esophagitis was diagnosed by biopsy. At autopsy, a fistulous tract was found extending from the esophagus to the aortic aneurysm; this fistula proved to be the site of fatal hemorrhage. The tract was surrounded by a granulomatous inflammatory reaction, in which acid-fast bacilli were found. To our knowledge, this is the first reported case of tuberculous esophagitis extending to an aortic aneurysm resulting in hemorrhage and death.
Patients with hospital-acquired lower respiratory infections pose both diagnostic and therapeutic challenges. Such infections are commonly seen in critically ill patients. When nosocomial pneumonia is suspected, treatment is generally initiated with broad-spectrum antibiotics before culture results become available. The usual therapeutic regimen includes an aminoglycoside with or without a beta-lactam agent. In a clinical efficacy study of a single agent, ceftazidime, in the treatment of 20 adults with hospital-acquired lower respiratory infection, 18 patients showed clinical improvement with ceftazidime therapy and pathogens were eradicated in 11. Therapeutic failures occurred in two patients who received empiric therapy prior to the isolation of pathogens resistant to ceftazidime. The median minimal inhibitory concentration of ceftazidime for the isolated pathogens was 0.78 micrograms/ml. Of the 15 patients infected with Pseudomonas aeruginosa, 14 showed a favorable clinical response. Therapy-limiting side effects occurred in two patients and bacillary resistance developed in one patient. The efficacy and safety of ceftazidime in the treatment of hospital-acquired pneumonias were comparable to results previously demonstrated for amikacin, cefotaxime, and imipenem in studies conducted at our institution. In studies reported in the literature, 44 of 51 patients (86 percent) with nosocomial pneumonia who were treated with ceftazidime had a favorable clinical response to therapy. The patients included in these studies were neither neutropenic nor commonly bacteremic, and none had cystic fibrosis. Ceftazidime appears to be a useful agent in the treatment of selected patients with nosocomial pneumonias, including those due to P. aeruginosa.
The effects of amphotericin B, ketoconazole, and adenine arabinoside on production of hepatitis B surface antigen (HBsAg) particles by the human hepatoma cell line PLC/PRF/5 were examined. In addition, the effects of these drugs on cellular protein synthesis were determined. These drugs caused a dose-dependent decrease in HBsAg production that was paralleled by a decrease in cellular protein synthesis. Ketoconazole was the most active of these drugs and the most specific, causing a 72% reduction in HBsAg production with only a 38% reduction in protein synthesis. These data suggest that further studies evaluating ketoconazole for the treatment of chronic hepatitis B virus infection in animals are warranted.
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