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Biomedical subjects

J M Leedom

Publications and source records attributed to J M Leedom.

At least 37 records · Page 2Linked to original sources

Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection.

PURPOSE: To determine the frequency with which the diagnosis of tuberculosis is delayed in patients with concomitant human immunodeficiency virus (HIV) infection, and to identify reasons for such delays. PATIENTS AND METHODS: We reviewed medical records of 52 consecutive HIV-infected patients with culture-proven tuberculosis seen at a 1,900-bed general hospital serving a predominantly indigent population in Los Angeles, where the prevalences of HIV infection and tuberculosis are high. The late-treatment (LT) group consisted of 25 patients in whom tuberculosis was untreated prior to death (n = 6) or treated more than 22 days after presentation (n = 19). The early-treatment (ET) group comprised 27 patients in whom antituberculous therapy was begun less than 16 days after presentation. RESULTS: Symptoms, physical and laboratory findings, chest roentgenographic abnormalities suggestive of tuberculosis (hilar adenopathy, pleural effusion, miliary pattern, cavitation, predominant upper lobe infiltrate), and frequencies of concomitant nontuberculous disease were similar in LT and ET groups. Delayed diagnosis of tuberculosis was attributable to errors in management in 21 (84%) of 25 LT group patients. The most common error was failure to obtain at least three sputum samples for acid-fast smear and mycobacterial culture in patients with clinical and chest roentgenographic findings compatible with tuberculosis (15 cases). Acid-fast sputum smears were positive in 25 (61%) of 41 cases of pulmonary tuberculosis. Acid-fast smears of stool were positive in eight (42%) of 19 cases. Blood cultures yielded Mycobacterium tuberculosis in 18 (38%) of 48 cases. CONCLUSIONS: Delayed therapy of tuberculosis in HIV-infected patients at our medical center was common and was not due to atypical manifestations of tuberculosis. In most cases, delays could have been avoided if adequate numbers of sputum samples for acid-fast smear and mycobacterial culture had been obtained, and if empiric antituberculous therapy had been given to symptomatic patients in whom chest roentgenographic findings were suggestive of mycobacterial disease.

Acquired Immunodeficiency Syndrome↗

Seronegative disseminated coccidioidomycosis in patients with HIV infection.

Serologic testing for complement-fixing antibodies to Coccidioides immitis is commonly employed to assist in the diagnosis and management of this infection, but its usefulness in an HIV-coinfected population is unknown. In this study we reviewed all the mycologically or histologically proven cases of disseminated C. immitis infection after 1982. Disseminated C. immitis and proven HIV infection were present in eight patients. We performed serum complement-fixing antibody titers on all eight patients, six of whom gave positive tests, while two patients (25%) gave repeatedly negative results despite widely disseminated disease. We conclude that histopathology and culture remain the most reliable methods for the diagnosis of disseminated coccidioidomycosis in the HIV-infected host.

Adult↗

A multicenter clinical trial of oral ribavirin in HIV-infected patients with lymphadenopathy. The Ribavirin-LAS Collaborative Group.

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin and placebo was conducted at four medical centers. One hundred sixty-four adult men with lymphadenopathy were enrolled over a 2-month period and randomized to receive ribavirin 800 mg (53 subjects), ribavirin 600 mg (55 subjects), or placebo (56 subjects). Active treatment was administered for 24 weeks followed by a 4-week washout period. Nine subjects receiving placebo, four receiving ribavirin 600 mg, and none in the 800 mg group developed AIDS during the 24 weeks of active treatment. One patient randomized to the 800 mg group had Kaposi's sarcoma at study entry and was included in the intent-to-treat analysis. An overall significant difference in progression to AIDS was observed among the three treatment groups (p = 0.028) with patients randomized to receive 800 mg having a significantly longer time to AIDS than placebo patients (p = 0.012; relative risk, 9.0; 95% confidence interval, 1.1 to 70.8). There was no significant difference between the 600 mg and placebo groups (p = 0.15; relative risk, 2.3; 95% confidence interval, 0.7 to 7.6). Baseline CD4 cell count and hematocrit made independent contributions and formed a multivariate prognostic set for these progression data. The significant treatment superiority of 800 mg compared to placebo remained after adjustment for these factors (p = 0.019). After deletion of patients with major protocol violations at entry, the difference between the 800 mg and placebo treatment remained significant (p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Cerebrospinal fluid cell counts and chemistries in bacterial meningitis.

We evaluated the records of 428 patients with bacterial meningitis to document initial cerebrospinal fluid (CSF) findings and detail their changes during therapy. Compared to patients with an initial polymorphonuclear cell predominance in the CSF, patients with initial CSF lymphocytosis had lower CSF leukocyte counts, milder CSF chemical abnormalities, and a lower frequency of positive CSF Gram stains and cultures. These findings suggest that CSF lymphocytosis may represent an early phase of infection. A low CSF leukocyte count was associated with a poor outcome, presumably reflecting an inadequate host response to infection. The CSF white cell count increased during the first 24 hours of therapy in 45% of cases. Morbidity and case fatality rates were not significantly increased in this group, suggesting that an initial rise in the CSF leukocyte count does not reflect a poor response to therapy.

Acute Disease↗

Predictors of short-term prognosis in patients with pulmonary tuberculosis.

We evaluated 191 consecutive adults with pulmonary tuberculosis in order to develop methods to determine which patients should be initially hospitalized. Using stepwise discriminant analysis, we found the six factors that were most strongly associated with an unfavorable short-term outcome (respiratory failure or death): lymphopenia, advanced age, concomitant smear-positive extrapulmonary tuberculosis, alcoholism, a high percentage of neutrophils on the differential white blood cell count, and lack of radiographic evidence of cavitation. We derived a scoring system incorporating these variables and separated patients into high- and low-risk groups. The system was prospectively validated by applying it to a separate group of 179 patients. Lymphocyte-transformation tests in 32 patients revealed an association between clinical markers of poor prognosis and minimal lymphocyte proliferation to a heat-killed strain of Mycobacterium tuberculosis.

Adolescent↗

Detection of cytomegalovirus DNA in peripheral blood of patients infected with human immunodeficiency virus.

Detection of cytomegalovirus (CMV) DNA can be facilitated by the polymerase chain reaction (PCR), an in vitro gene amplification technique. Twenty-eight CMV tissue culture isolates were examined by amplification of two separate CMV genes. All were found to contain CMV, although two of the isolates were positive for only one of the two genes. No detectable amplification occurred with human genomic or other viral DNA controls. The amplification products from as few as one CMV plaque-forming unit could be detected after the PCR. CMV DNA was detected in the blood of 14 of 27 patients with AIDS and one of six patients who were infected with human immunodeficiency virus but who did not have AIDS. Normal CMV-seropositive or -seronegative individuals did not have CMV DNA detected in their blood. The CMV PCR was more sensitive than the standard culture assay, can be completed in one to two days, uses only 20 microL of blood, and may be useful for rapidly detecting CMV in clinical specimens.

Acquired Immunodeficiency Syndrome↗

Chest roentgenogram in pulmonary tuberculosis. New data on an old test.

The utility of routine admission chest roentgenograms (CXRs) was evaluated in detecting pulmonary tuberculosis and the relationship between roentgenographic patterns and the likelihood of finding acid-fast bacilli (AFB) on sputum smear. Of 58 patients whose chief complaints were unrelated to pulmonary tuberculosis, the CXR suggested tuberculosis in 52 cases (90 percent). In 45 cases, the emergency room physician failed to elicit the patient's respiratory symptoms and did not consider tuberculosis as a diagnostic possibility. In 18 individuals, the diagnosis was missed in the emergency room because of failure to obtain a CXR. Among patients whose roentgenograms showed cavitation or extensive alveolar infiltrate, sputum smears showed AFB in 98 percent of cases. If alveolar infiltrate was absent, or if the roentgenographic pattern was not that of adult reactivation disease, sputum smears revealed AFB in only one half of the cases. We conclude that routine admission CXRs are useful in hospitals serving populations where tuberculosis is still common, and the probability of detecting AFB on sputum smear is greatly influenced by the roentgenographic findings.

Adolescent↗

Norfloxacin in the eradication of enteric infections in AIDS patients.

Recurrent episodes of salmonellosis, including recurrent life-threatening bacteremias, have been well-described in patients with AIDS. Because of the need to avoid sensitization to trimethoprim-sulfamethoxazole (TMP-SFX) in AIDS patients and the high frequency of ampicillin resistance of Salmonella isolates, alternative therapies must be sought. We report the treatment of nine AIDS patients, who had recurrent salmonellosis, with norfloxacin, a new oral fluoroquinolone which has excellent in vivo activity against Salmonella sp. Each patient had two to three prior distinct clinical episodes of salmonellosis which had failed to be eradicated with standard courses of ampicillin, TMP-SFX, ceftriaxone or cefotaxime. Microbiologic relapse had occurred in each patient within 2-4 weeks. Each of the enteric pathogens was susceptible in vitro to norfloxacin. Patients were treated with norfloxacin 400 mg bid orally for 30 days. Stool cultures were negative at 1 week in all patients. Nausea and headache were the only adverse reactions to norfloxacin noted. One patient had a clinical and microbiologic relapse of Salmonella 1 week after norfloxacin was stopped but responded to retreatment with norfloxacin. Norfloxacin appears effective in the treatment of enteric infections in AIDS patients and may be more useful than standard agents in eradicating the organism and preventing clinical and microbiologic relapse. Oral administration and twice daily dosing are significant advantages.

Acquired Immunodeficiency Syndrome↗

Rattlesnake capsule-associated Salmonella arizona infections.

Three Hispanic patients at our institution developed extragastrointestinal Salmonella arizona infection associated with the ingestion of rattlesnake capsules. All patients had underlying chronic medical illnesses, including the acquired immunodeficiency syndrome, systemic lupus erythematosus, and congestive heart failure. Rattlesnake capsules were obtained from both local pharmacies and patients. Salmonella arizona, as well as various other enteric organisms, was grown on cultures obtained from all capsules tested. Review of the literature disclosed three additional cases of extragastrointestinal S arizona infection linked to rattlesnake capsule ingestion, all associated with underlying medical illness. We postulate that rattlesnake capsules may be frequently ingested by chronically ill Hispanic individuals and serve as a vehicle for serious S arizona infection.

Adult↗

The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.

AIDS-Related Complex↗

The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial.

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

AIDS-Related Complex↗

Imipenem therapy for perforated and gangrenous appendicitis.

A matched patient control study of imipenem therapy of patients with perforated or gangrenous appendicitis was performed. Thirty-three patients treated with imipenem and cilastatin were compared with 66 control patients treated with clindamycin and gentamicin. Patients were matched for age and surgical pathologic factors. Twenty-five of the 33 imipenem treated patients had perforated (two with abscesses) and nine had gangrenous appendicitis. Anaerobes were recovered from 23 of 32 (72 per cent), anerobes from 31 of 32 (97 per cent) and Pseudomonas from six (26 per cent) of the 23 with perforated appendicitis. Only one isolate, a Fusobacterium species was resistant to imipenem. Enterococci were isolated only from three imipenem treated patients, all were susceptible and were not associated with failures. Frequency of other pathogens isolated was similar for the imipenem and clindamycin and gentamicin patients. One failure occurred in the imipenem treatment group. Failures and adverse reactions were not different for the two groups. The study would have detected as significant (p equals 0.03) a 9 per cent difference in failure rates. Mean days of fever of more than 38 degrees C and days of hospitalization were fewer (p less than 0.05) for imipenem treated patients even when only patients with perforated appendicitis were compared. Days to return of intestinal function were fewer for control patients. Imipenem and cliastatin appeared to be an effective antimicrobial agent used as an adjunct to surgical treatment for peritonitis associated with appendicitis even when caused by Bacteroides fragilis group organisms or Pseudomonas species, or both.

Adult↗

Comparative in vitro activities of norfloxacin (MK-0366) and six commonly used antimicrobial agents against 199 urinary isolates showing various degrees of antibiotic resistance.

The in vitro activity of norfloxacin (MK-0366), a new oral antimicrobial agent, was compared to that of ampicillin, tetracycline, cefazolin, nitrofurantoin, nalidixic acid, and trimethoprim against 199 gram-negative urinary isolates. Among these isolates were ampicillin-resistant Escherichia coli and gentamicin-resistant Pseudomonas aeruginosa and Serratia marcescens. Norfloxacin was the most active antimicrobial agent tested against all isolates studied; it was the only agent active against P. aeruginosa and S. marcescens.

Anti-Infective Agents, Urinary↗