Electrical impedance measurements with the CI24M cochlear implant for a child with Mondini dysplasia.

Electrical impedance measurements can give useful information about the status of individual electrodes of a cochlear implant. Impedances within the normal range (when measured in the common ground mode of stimulation) suggest that current flow occurs in the tissue and fluid of the cochlea. Low impedance measurements may suggest that particular electrodes are short circuiting, whereas high impedances might be due to a broken electrode wire or an electrode only in contact with air. In the case discussed, low impedance measurements were recorded intra-operatively from a child with Mondini dysplasia on electrodes 1-13 of a Nucleus CI24M device. Post-operatively the impedances had returned to the expected range and were comparable with other patients implanted with the CI24M device. Possible reasons for this are discussed. It was thought that impedances were low intra-operatively due to a larger-than-normal proportion of fluid surrounding the electrode array, rather than short circuits occurring along the array, as suggested by the dps7 software.

Evaluation of an enzyme-linked immunosorbent assay that uses ferrous metal beads for determination of antihistoplasmal immunoglobulins G and M.

A rapid enzyme-linked immunosorbent assay (ELISA) for the detection of human class-specific antibodies to Histoplasma capsulatum (histoplasmal immunoglobulin M [HIgM] and histoplasmal IgG [HIgG]) was developed by using antigen adsorbed onto polycarbonate-coated ferrous beads. In the ELISA method all the reagents used were commercially available. In 135 specimens from patients with confirmed histoplasmosis, sensitivities were 76% for complement fixation (CF), 53% for immunodiffusion (ID), and 64% for the ELISA for HIgM and HIgG combined. The ELISA detected histoplasmal antibody in 36% of the specimens with negative antibody titers by CF and 46% of the specimens with negative antibody titers by ID. The ELISA detected histoplasmal antibody in 27% of specimens that were negative by both CF and ID. When limited to specimens collected within 4 months of the onset of histoplasmosis symptoms, sensitivities were 82% for CF, 63% for ID, and 86% for ELISA for HIgG and HIgM combined. Within this group, ELISA detected histoplasmal antibody in 90% of the specimens that were negative by CF, 76% that were negative by ID, and 100% that were negative by both CF and ID. The specificity of the ELISA could not be fully addressed since sera from patients with other fungal infections were not available.

Sarcoidlike manifestations of histoplasmosis.

We have evaluated 11 patients with sarcoidosis accompanied by laboratory evidence for histoplasmosis. Clinical findings were typical of those described in sarcoidosis. Eight patients were treated with corticosteroids and responded promptly without progression of histoplasmosis. One patient received a 35 mg/kg course of amphotericin B without clinical improvement, but responded appropriately to corticosteroid therapy. Another patient had positive sputum cultures for Histoplasma capsulatum 5 years after initial diagnosis of sarcoidosis, but showed no improvement in the pulmonary infiltrate after treatment with amphotericin B. Although histoplasmosis and sarcoidosis may be interrelated in several ways, we postulate that H capsulatum may have triggered a chronic inflammatory disease recognized as sarcoidosis in some of these patients, a hypothesis yet to be tested. Alternative explanations for the association of histoplasmosis and sarcoidosis include the coincidental occurrence of two separate illnesses in a "hyperendemic" area for histoplasmosis and false-positive serologic test results caused by the heightened humoral immune response observed in sarcoidosis.

Comparison of sandwich solid-phase radioimmunoassay and two enzyme-linked immunosorbent assays for detection of Histoplasma capsulatum polysaccharide antigen.

Detection of a Histoplasma capsulatum polysaccharide antigen (HPA) has proved a useful approach to diagnosis of histoplasmosis. Two sandwich enzyme-linked immunosorbent assays (ELISAs) using alkaline phosphatase (AP)-or horseradish peroxidase (HRP)-conjugated antibodies were compared with solid-phase radioimmunoassay (RIA) for detection of HPA. The AP-ELISA and HRP-ELISA were each positive in 17 (89.5%) of 19 urine specimens from patients with disseminated histoplasmosis, while the RIA was positive in 18 (94.7%) of 19. Specimens from patients with nondisseminated histoplasmosis were positive by AP-ELISA in 8 of 32, by HRP-ELISA in 4 of 25, and by RIA in 12 of 25. Of control specimens from patients with other fungal infections, the AP-ELISA was negative in 22 (91.7%) of 24, the HRP-ELISA in 23 (95.8%) of 24, and the RIA in 23 (95.8%) of 24. Reproducibilities AP-ELISA and HRP-ELISA were 95.1% and 95.1%, respectively. Thus, AP-ELISA and HRP-ELISA appear less sensitive than RIA and may be falsely negative in specimens containing low levels of HPA.

Clinical experience with cytomegalovirus isolation using conventional cell cultures and early antigen detection in centrifugation-enhanced shell vial cultures.

A total of 1,915 clinical samples was inoculated by low-speed centrifugation into shell vials (Bartels Immunodiagnostics, Bellvue, Wash.) containing cover slip monolayers of MRC-5 fibroblasts. At 1 and 2 days postinoculation, one cover slip was stained by an indirect immunofluorescence technique using a monoclonal antibody (Biotech Research Laboratories for Dupont, Billerica, Mass.) to cytomegalovirus (CMV) early antigen (EA). Clinical samples were also inoculated into three MRC-5 or MRHF cell cultures which were observed for 30 days for the appearance of a cytopathic effect (CPE). Of 157 CMV-positive samples, 92 (59%) were identified by centrifugation-enhanced EA (CE-EA) and 131 (83%) produced a CPE. CE-EA was less sensitive than CPE for all types of samples, although 17% of CMV-positive samples were detected by CE-EA alone. Evaluation of the CMV status of patients with CE-EA-positive-CPE-negative samples indicated that these samples likely represented true CMV-positive results. The average elapsed time between culture inoculation and identification of CMV decreased as follows when both CE-EA and CPE, rather than CPE alone, were used: urines, 15 to 7 days; buffy coats, 18 to 9 days; lung samples, 13 to 8 days; throat samples, 18 to 7 days. Although CE-EA was less sensitive than 30-day cell culture, both CE-EA and CPE were identified as valuable in CMV detection, and neither could be discontinued without a decrease in the CMV isolation rate or an increase in the turnaround time.

Significance of Histoplasma antigen in the cerebrospinal fluid of patients with meningitis.

A radioimmunoassay was previously developed for detection of Histoplasma capsulatum antigen in the blood and urine of patients with disseminated histoplasmosis. In this investigation, cerebrospinal fluid (CSF) specimens from 14 episodes of Histoplasma meningitis occurring in 12 patients were tested by radioimmunoassay. Histoplasma capsulatum antigen was detected in the CSF of five patients. Cerebrospinal fluid cultures were positive for H capsulatum in three of these five patients. Antibodies to H capsulatum were found in nine of the 13 CSF specimens tested. The radioimmunoassay for Histoplasma antigen was also positive in the CSF in one of 11 patients with coccidioidal meningitis but not in 17 patients with cryptococcal meningitis. It was concluded that Histoplasma antigen is present in the CSF of some patients with histoplasmosis and chronic meningitis, but cross-reactions may occur in patients with coccidioidal meningitis.

Evaluation of four methods for cytomegalovirus antibody detection for use by a bone marrow transplantation service.

Four methods, latex agglutination, indirect fluorescent antibody, enzyme immunoassay, and complement fixation, were compared for cytomegalovirus antibody screening and for pre- and posttransplant determinations on bone marrow transplant recipients. Latex agglutination was most sensitive (98%) and specific (97%) for screening and pretransplant determinations and was quickest and easiest to perform. In posttransplant sera from allogeneic bone marrow transplant recipients, all methods except complement fixation detected cytomegalovirus antibody from therapeutically administered globulin preparations; this made it difficult to determine the significance of changes in cytomegalovirus antibody titer.

Neurologic complications in oral polio vaccine recipients.

Between April 1982 and June 1983 four children 3 to 24 months of age were referred for evaluation of neurologic abnormalities found to be compatible with vaccine-related poliovirus infection, which had not been suspected by referring physicians. Patients were epidemiologically unrelated residents of Indiana, and none had prior symptoms suggestive of immunodeficiency. All had received poliovirus vaccine orally (first dose in three, fourth dose in one) and a diphtheria-tetanus-pertussis injection in the left anterior thigh within 30 days of symptoms. A vaccine-like strain of poliovirus was isolated from each patient, and each had symptoms (left leg paralysis in three; developmental regression, spasticity, and progressive fatal cerebral atrophy in one) persisting for at least 6 months. Immune function was normal in two with poliovirus type 3 infection, and abnormal (hypogammaglobulinemia, combined immunodeficiency) in two with type 1 and type 2 infection, respectively. The incidence of observed vaccine-related poliovirus infection in Indiana recipients of orally administered poliovirus vaccine was 0.058 per 100,000 per year, significantly greater (P less than 0.001) than predicted.

Adaptation of a commercially available indirect fluorescent antibody slide test for measuring measles-specific immunoglobulins.

A commercially available indirect fluorescent antibody (IFA) test was evaluated for the determination of measles-specific immunoglobulins G and M (MIgG, MIgM). The IFA test detected fourfold rises of MIgG in 34 of 35 (97%) cases of measles confirmed by complement fixation or hemagglutination inhibition. In determining immune status, MIgG-IFA correlated with hemagglutination inhibition in 22 of 23 (96%) cases. The IFA test detected MIgM in only 11 of 34 acute-phase sera collected within 5 days of the reported onset of rash and in the convalescent specimens of another 13 of the 35 specimens. The IFA test is an effective method for the conventional diagnosis of measles and for determining immune status. This IFA test has a limited role as a rapid diagnostic test for measles when used to detect measles-specific MIgM in acute-phase sera obtained from patients with suspected measles.

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.

Cross-reactive urinary antigens among patients infected with Legionella pneumophila serogroups 1 and 4 and the Leiden 1 strain.

A solid-phase radioimmunoassay was developed to detect antigens of Legionella pneumophila serogroup 4. The assay detected antigen in urine from four of seven patients with pneumonia caused by L. pneumophila serogroup 4, two of two patients with L. pneumophila Leiden 1 strain (proposed new serogroup), and 26 of 55 patients with L. pneumophila serogroup 1 (proven by culture or direct fluorescent-antibody assay). The antigen of two patients with serogroup 4, one with Leiden 1 strain, and 49 with serogroup 1 infections could be detected in a previously described assay for antigens of L. pneumophila serogroup 1. Serogroup specificity of the assays could be demonstrated if serial dilutions of urine were tested. None of 347 urine specimens used as controls were positive in the radioimmunoassay. We conclude that antigens are excreted in the urine of at least some patients with Legionnaires' disease caused by serogroup 4 and Leiden 1 strain. The urinary antigens in patients with serogroup 4 and Leiden 1 strain infections, although different from those in patients with serogroup 1 infections, serologically contain cross-reactive components.

Women at risk for gonorrhea: comparison of rosaramicin and ampicillin plus probenecid in the eradication of Neisseria gonorrhoeae, Chlamydia trachomatis and genital mycoplasmas.

Rosaramicin is a macrolide antibiotic with activity against Neisseria gonorrhoeae, Chlamydia trachomatis, and the genital mycoplasmas Ureaplasma urealyticum and Mycoplasma hominis. Its efficacy in the treatment of genital infections was evaluated and compared with that of single-dose ampicillin plus probenecid in women with known, or suspected, uncomplicated gonococcal infection. Isolation rates for N. gonorrhoeae, C. trachomatis, U. urealyticum, and M. hominis were 72%, 44%, 95%, and 65%, respectively. Rosaramicin cured 24 (89%) of 27 gonococcal infections and 11 (92%) of 12 chlamydial infections. It transiently reduced the carriage of U. urealyticum but had little effect on carriage of M. hominis. Rosaramicin may be of value in the treatment of concurrent gonococcal and chlamydial infections when tetracycline is contraindicated.

Cavitary histoplasmosis occurring during two large urban outbreaks. Analysis of clinical, epidemiologic, roentgenographic, and laboratory features.

We have compared risk factors for cavitary histoplasmosis in 62 patients with that manifestation of the infection and in 679 patients with other forms of histoplasmosis, and we have evaluated the clinical and laboratory findings in 45 patients with cavitary histoplasmosis who were cared for at the Indiana University Medical Center hospitals during two large histoplasmosis outbreaks. Chronic obstructive lung disease and old age were the strongest risk factors for cavitary histoplasmosis but male sex, white race and immunosuppression were also important in certain patient groups. Fever, sweats, weight loss, productive cough, anemia, lymphopenia, and alkaline phosphatase elevation were common findings. The patients were occasionally incorrectly treated for presumed class 3 tuberculosis. Cultures were positive in 58% of patients, with sputum samples providing the highest yield (61%). Histoplasmal serologic tests provided useful clues to the diagnosis, positive in over 90% of cases. About one-third of patients recovered spontaneously while another 35% improved following treatment. About 4% developed chronic untreated cavitary histoplasmosis characterized by clinical and roentgenographic exacerbations and remissions. Of the deaths in four patients with untreated disease, one was caused by disseminated histoplasmosis while three died of other causes. Ketoconazole appeared effective in three of seven patients while its effect in three additional patients was uncertain. Toxicity precluded completion of ketoconazole therapy in one patient. Only amphotericin B has been proven to be effective therapy for cavitary histoplasmosis.

Differentiation of lymphoma from histoplasmosis in children with mediastinal masses.

The differentiation of mediastinal masses caused by lymphoma from those caused by histoplasmosis may require thoracotomy. We reviewed the medical records of 37 children undergoing initial evaluation for anterior or middle mediastinal masses. Sixteen had biopsy-proved lymphoma, and 21 had histoplasmosis; seven with histoplasmosis underwent thoracotomy. Age, sex, fever, weight loss, duration of illness, anemia, erythrocyte sedimentation rate, nonspecific reactants, and lung infiltrates and calcifications were similar in both groups. Masses were in the middle mediastinum in all patients with histoplasmosis and in 69% with lymphoma. Masses were in the anterior mediastinum in one of 21 (5%) with histoplasmosis and 13 of 16 (81%) with lymphoma. Among patients with lymphoma, histoplasmal complement fixation antibody titers were less than 1:8 in 14 of 15 (93%); a single patient had a titer of 1:16. The CF titers were greater than or equal to 1:32 in 14 of 21 (67%) with histoplasmosis. In children with middle mediastinal masses, a histoplasmal CF yeast or mycelial titer greater than or equal to 1:32 is strongly suggestive of acute histoplasmosis and biopsy is not required. Children not fulfilling these criteria should undergo diagnostic biopsy.

Recurrent urban histoplasmosis, Indianapolis, Indiana, 1980-1981.

In January 1981, informal surveillance of acute histoplasmosis in Indianapolis, Indiana, revealed a marked increase in disease activity for the last quarter of 1980. Fifty-one patients with onset of acute histoplasmosis during this period were identified through review of hospital admissions, emergency room visits, and serologic records at Indianapolis hospitals and the Indiana State Board of Health. In a retrospective case-control study, the authors found a significant association between developing acute histoplasmosis during this period and working or attending classes in a 2 sq mi (5.2 sq km) area encompassing the Indiana University-Purdue University campus (p = 0.015, Fisher's exact test). A review of construction activities on or near the campus during the epidemic period suggested that the probable source of infection was excavation activity for a large new indoor swimming complex (natatorium). Skin tests and serosurveys of students on campus by a newly developed radioimmunoassay for histoplasmal immunoglobulin M antibodies supported the association of infection with exposure to this site (p less than 0.05).

Rapid diagnosis of measles using enzyme-linked immunosorbent assay for measles immunoglobulin M.

An enzyme-linked immunosorbent assay (ELISA) for measles-specific immunoglobulin M (MIgM) was developed for use as a rapid diagnostic test for acute measles. A titer greater than or equal to 1:20 in both the acute and convalescent sera was present in 100% of patients with measles and was diagnostic of acute measles infection in children. Interference by rheumatoid factor (RF) was avoided by pretesting sera for RF and absorption with aggregated gamma globulin. Ion exchange separation of IgM and IgG should eliminate RF interference. The ELISA MIgM assay can easily be used in any laboratory for the serologic confirmation of measles infection.

Immunoglobulin M and G histoplasmal antibody response in histoplasmosis.

Radioimmunoassays for IgM and IgG histoplasmal antibodies were developed and proved to be specific for their respective immunoglobulin classes, sensitive, and reproducible. Elevated IgM antibodies were detected in 59.8% of patients with histoplasmosis and 7.9% of control subjects. Elevated IgG antibodies occurred in 80.4% of patients with histoplasmosis but in only 12.9% of control subjects. Radioimmunoassay was nearly twice as sensitive as complement fixation for identifying patients with mild, presumably asymptomatic, infection. Of 13 patients with serologic follow-up at least 1 yr later, elevated IgM antibodies cleared, whereas IgG antibodies persisted in 7. In an epidemiologic investigation of a recurrent histoplasmosis outbreak, only the radioimmunoassay was able to prove the hypothesis that construction for a swimming complex was the source of exposure. These assays promise to be useful for clinical and epidemiologic investigations.