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Biomedical subjects

J Wheat

Publications and source records attributed to J Wheat.

33 records · Page 2Linked to original sources

Histoplasmosis and coccidioidomycosis in individuals with AIDS. A clinical review.

Histoplasmosis and coccidioidomycosis are serious opportunistic infections in patients with AIDS residing in endemic areas of the United States and Central and South America. Prompt diagnosis requires knowledge of the clinical syndromes and diagnostic tests as well as a high index of clinical suspicion. Histoplasmosis responds well to a variety of treatments but relapses without chronic suppressive antifungal therapy. Improvements in treatment are needed in coccidioidomycosis. Research is needed to identify preventive strategies in at risk patients. These may include use of prophylactic antifungal therapy or vaccination.

AIDS-Related Opportunistic Infections↗

Objective decision-making following a portal film: the results of a pilot study.

PURPOSE: To discriminate between random and systematic treatment setup errors using portal films. METHODS AND MATERIALS: A bi-dimensional analytic techniques using multiple analyses of variance based on Hotelling's T2 statistics to derive numerical and graphical measures of daily portal film accuracy and precision has been trialed using 88 daily portal films from seven patients' treatment. RESULTS: A demonstration is provided of how a reasonable approximation of random variation from the intended (Simulator) field center, and systematic displacement of the mean position of the portal film centers may be derived from a minimum number of portal films. If a random error as great as 10 mm exists, at least six or seven portal films are considered necessary to reliably detect and quantify the size of a systematic error. CONCLUSION: Our results suggest that a modest systematic error could go undetected until the end of a 5 or 6 week course of treatment if only one portal film is obtained each week. A greater number of portal films should be performed during the first week of treatment to reduce the frequency of such errors. Efforts to separate and quantify both random and systematic errors in setup are worthwhile and will lead to improvements in outcome at the individual patient level and at a departmental level in the development of quality assurance programs.

Humans↗

Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. SETTING: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). PATIENTS: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. INTERVENTIONS: Itraconazole, 200 mg given orally twice daily. MAIN OUTCOME MEASURES: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. RESULTS: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). CONCLUSIONS: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy.

AIDS-Related Opportunistic Infections↗

Chronic osteomyelitis caused by Staphylococcus aureus: controlled clinical trial of nafcillin therapy and nafcillin-rifampin therapy.

A controlled trial of treatment of chronic osteomyelitis caused by Staphylococcus aureus compared nafcillin alone with nafcillin plus rifampin for a six-week period. Treatment was well tolerated, the only adverse effect being mild neutropenia in four of 18 patients; no toxicity was observed from rifampin. Eight of ten patients in the combined treatment group had a favorable clinical response (with follow-up of two to four years) as compared to four of eight in the nafcillin group (P = .2). Despite the failure to show a statistically significant advantage of rifampin plus nafcillin, we conclude that the combination, along with appropriate surgery, should be considered for patients with chronic staphylococcal osteomyelitis.

Administration, Oral↗

Evaluation of cross-reactions in Histoplasma capsulatum serologic tests.

Cross-reactivity in Histoplasma serologic tests was evaluated by using sera from patients with histoplasmosis and other infections. Serum samples from 127 of 134 (95%) patients with histoplasmosis were judged positive by complement fixation tests, and 121 (90%) showed H bands, M bands, or both by immunodiffusion. Of these 134 patients, cross-reactions were seen to Blastomyces dermatitidis in 53 patients (40%), to Coccidioides immitis in 20 patients (16%), and to Aspergillus fumigatus in 3 patients (2%) by complement fixation. Serum samples from 5 of 99 patients (5%) with other fungal infections and from 5 of 46 patients (11%) with tuberculosis had M precipitin bands by the Histoplasma immunodiffusion test, whereas none of the 123 sera from patients with other bacterial, Mycoplasma, or viral infections showed H or M precipitin bands. In the complement fixation test, positive reactions were observed in 16 of 90 patients (18%) with other fungal infections, in 14 of 41 patients (34%) with tuberculosis, and in 18 of 105 patients (17%) with other bacterial, Mycoplasma, or viral infections. Positive reactions were seen by radioimmunoassay in 54 of 110 patients (49%) with other fungal infections, in 23 of 46 patients (50%) with tuberculosis, and in 35 of 123 patients (28%) with with other bacterial, Mycoplasma, or viral infections. These results demonstrate a wider range of cross-reactions in Histoplasma serology than has been previously recognized, and the cross-reactivity was greatest when observed by radioimmunoassay. Caution should be exercised in the interpretation of serologic data from patients with suspected fungal infections.

Antibodies, Fungal↗

Diagnostic strategies in osteomyelitis.

Technetium-99 (99Tc) pyrophosphate bone scanning often identifies patients with osteomyelitis before roentgenographic findings appear. However, recent studies have shown that 99Tc bone scanning often gives false-negative results, especially in neonates. The accuracy of computed tomographic scanning and indium-111 leukocyte scanning for diagnosis of early osteomyelitis has not been established. 99Tc bone scanning often gives false-positive results in patients with other conditions leading to bone injury and repair, such as trauma or recent surgery, further limiting the usefulness of this imaging procedure. Newer imaging techniques have not been adequately evaluated to establish their specificity. Because of their high cost and unproved accuracy, these new imaging procedures should not be routinely applied until their usefulness has been established. Bone biopsy remains the procedure of choice for establishing the diagnosis in patients suspected clinically to have osteomyelitis with negative findings on roentgenography and 99Tc bone scanning. Although Staphylococcus aureus is the leading cause of osteomyelitis, other pathogens cause 30 to 40 percent of cases. Aspiration or biopsy of the involved bone is usually required to choose appropriate antibiotic therapy. Bone biopsy is essential in chronic osteomyelitis, since cultures of sinus drainage are unreliable. Osteomyelitis in diabetics with foot infection and in association with decubitus ulcers presents special problems. Radionuclide scanning often give false-positive results in these patients. Proper diagnosis usually requires careful assessment of clinical and roentgenographic findings. Although bone biopsy seems useful in diagnosing osteomyelitis underlying decubitus ulcers, its role in diabetic patients with foot infections is not established. I do not recommend biopsy of foot bones in diabetic patients, since culture of bone biopsy specimens often give unreliable results in these situations because of contamination with ulcer organisms.

Acute Disease↗

Humoral and cellular immune response in ocular histoplasmosis.

We have compared several humoral and cellular immune responses in ocular and in acute histoplasmosis syndromes. T-lymphocyte subset analysis revealed elevated ratios of T-helper/T-suppressor lymphocytes in ten of 22 patients with ocular histoplasmosis, whereas ratios were depressed in 18 of 22 with acute histoplasmosis syndromes. Lymphocyte transformation responses to mitogens and to histoplasma antigens were similar in both acute and ocular histoplasmosis. However, histoplasma antibody levels as measured by immunodiffusion, complement fixation, and radioimmunoassay were elevated in only three of 22 patients with ocular histoplasmosis, compared with 18 of 22 with acute histoplasmosis. Natural killer cell cytotoxicity was depressed in ten of 20 patients with ocular histoplasmosis compared with none of 18 with acute histoplasmosis. These findings support the clinical observations that ocular histoplasmosis and acute histoplasmosis syndrome are seldom, if ever, seen in the same patient.

Antibodies, Fungal↗

Cerebrospinal fluid Histoplasma antibodies in central nervous system histoplasmosis.

We have evaluated the Histoplasma antibody response in the cerebrospinal fluid (CSF) in nine patients with central nervous system histoplasmosis and 98 controls. While the CSF Histoplasma antibody response identified eight of the nine patients, CSF cultures were positive in only two. Of controls with histoplasmosis but without meningitis (13 patients), or without histoplasmosis (85 patients), elevated CSF antibodies were detected by complement fixation in seven, by IgG radioimmunoassay in 17, and by IgM radioimmunoassay in five. Measurement of the CSF Histoplasma antibody response appears useful for identifying meningitis in patients with histoplasmosis, although cross-reactions occur in half of patients with other forms of chronic fungal meningitis. Patients with these other infections can usually be identified by tests for CSF Coccidioides antibodies, or cryptococcal antigens.

Antibody Formation↗

Commercially available (ENDO-STAPH) assay for teichoic acid antibodies. Evaluation in patients with serious Staphylococcus aureus infections and in controls.

We have evaluated the clinical usefulness of a commercially available teichoic acid antibody assay (ENDO-STAPH). Teichoic acid antibody titers up to a 1:2 serum dilution were observed in 20% of normal subjects, thus, titers of 1:4 or more were considered positive. Of patients with Staphylococcus aureus infections, 16 of 23 with endocarditis, 12 of 20 with complicated bacteremia, three of 17 with uncomplicated bacteremia, and ten of 20 with nonbacteremic infections had positive titers. Only four of 70 controls had positive titers. Results agreed with those using our standard assay in 130 of 151 specimens. Results were reproducibly positive or negative in 17 of 18 specimens that were retested. Results were also reproducible in ten specimens retested using a different lot of standardized antigen. The ENDO-STAPH assay should broaden the clinical applications of assays for TAA.

Antibodies, Bacterial↗

Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks.

Clinical and laboratory features have been reviewed in 66 episodes of disseminated histoplasmosis that occurred during two large urban outbreaks in Indianapolis. Immunosuppression, age greater than 54 years, and presence of other serious underlying illnesses predisposed to the disseminated form of the disease; only 21% of patients lacked one of these risk factors. Central nervous system findings, splenomegaly, hepatomegaly, and lymphopenia suggested disseminated disease but were present in only about one-third of patients. Miliary or diffuse pulmonary infiltrates also suggested dissemination and were noted in about one-third of patients, while mediastinal lymphadenopathy was present in only 17%. Histoplasmal serologic tests, positive in 90% of patients, provided useful diagnostic clues. The diagnosis could be confirmed by culture in 88% of patients, and special stains were positive in about two-thirds. Although 10% of patients recovered without treatment, 11 patients (17%) died because of failure to suspect the diagnosis and initiate therapy promptly. Amphotericin B was effective in all patients receiving at least 500 mg, but relapse occurred if the total dose was less than 30 mg/kg. Ketoconazole appeared effective in non-immunosuppressed patients but not in those with underlying immunosuppression; however, a controlled trial comparing ketoconazole and amphotericin B is required to establish the role of this new fungistatic oral agent.

Adolescent↗

The diagnostic laboratory tests for histoplasmosis: analysis of experience in a large urban outbreak.

Of 495 patients reported in a large urban histoplasmosis outbreak, we studied 276 whose serologic tests were done in a single laboratory. Serologic test results were positive in 96% of these patients (compared with less than 5% of controls from an endemic area), cultures were positive in 22%, and special stains in 19%. The immunodiffusion test results were negative in 13% of patients who had positive findings by complement fixation, and 1% had positive results only by immunodiffusion. The complement fixation test was almost twice as sensitive as the immunodiffusion test in patients with subclinical infection. The serologic response differed significantly among the clinical syndromes with higher titers in cavitary and lower titers in disseminated disease. Factors associated with titers of 1:64 or greater to both antigens were black race and immunocompetence. High mycelial titers were also associated with more intense exposure, and high yeast titers were associated with age less than 36 years. No prognostic significance could be proved for fourfold titer rises or falls or persistence of precipitins.

Adolescent↗

Endocarditis caused by Actinobacillus actinomycetemcomitans.

A case of endocarditis caused by Actinobacillus actinomycetemcomitans is described and 18 cases are reviewed. Clinical features of endocarditis caused by A actinomycetemcomitans and antibiotic susceptibility are reviewed. Because of the relative resistance of A actinomycetemcomitans to penicillin and ampicillin, high doses of either penicillin or ampicillin should be combined with streptomycin or gentamicin for four to six weeks.

Actinobacillus↗