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Biomedical subjects

T Cleary

Publications and source records attributed to T Cleary.

At least 19 recordsLinked to original sources

Multidrug-resistant tuberculous meningitis in patients with AIDS.

We present clinical manifestations, bacteriologic characteristics, and outcomes for eight patients with multidrug-resistant (MDR) tuberculous meningitis and AIDS. All developed meningitis as a terminal complication of previously diagnosed MDR-TB despite anti-tuberculosis therapy. Seven patients presented with fever, five with headache, four with altered mentation, two with focal deficits and one with seizures. CSF examination revealed pleocytosis, hypoglychorrhachia and elevated protein. Mycobacterium tuberculosis resistant to at least isoniazid and rifampin was isolated from all patients. Intracerebral mass lesions were detected in three patients, hydrocephalus in three, meningeal enhancement in five, and infarcts in two. Seven patients died 1-16 weeks after the diagnosis of meningitis; the eighth was lost to follow-up. MDR tuberculous meningitis is a difficult-to-treat infection with a high fatality rate.

AIDS-Related Opportunistic Infections↗

Cerebral phaeohyphomycosis due to a novel species: report of a case and review of the literature.

Cerebral phaeohyphomycosis is a rare disease caused by dematiaceous (darkly pigmented) fungi. Cladophialophora species are highly neurotropic, and Cladophialophora bantiana (synonym=Xylohypha bantiana or C. trichoides) is the most commonly identified agent. Most reported cases of cerebral phaeohyphomycosis have occurred in immunocompetent patients; however, some case reports and experimental data have suggested that cellular immune deficiency is a risk factor. We report a case of pulmonary and cerebral phaeohyphomycosis in a cardiac transplant patient due to a newly identified species of Cladophialophora. Optimal management includes both antifungal therapy and surgery.

Adult↗

Rapid and specific detection of the Mycobacterium tuberculosis complex using fluorogenic probes andreal-time PCR.

A rapid and sensitive strategy for the specific identification of Mycobacterium tuberculosis (TB) was designed and evaluated using crude mycobacterial lysates. The speed of real-time polymerase chain reaction (PCR) was combined with the sensitivity of fluorogenic probes to confirm the presence of mycobacteria as well as specifically identify the presence of members of the mycobacteria tuberculosis complex (MTC) in a single-tube assay. Oligonucleotides were designed to amplify the internal transcribed spacer (ITS) from several mycobacterial species. Specific fluorogenic probes were included in the PCR reaction for the identification of TB as well as Mycobacterium bovia and Mycobacterium africanum in bacterial lysates. The combination of TB-specific fluorogenic probes with real-time PCR formed an approach determined to be fast (less than 40 min), sensitive (less than 800 copies of DNA) and reliable for the specific detection of the MTC. Our data demonstrate the use of real-time PCR and fluorogenic probes in a rapid and sensitive assay to distinguish members of the MTC from other mycobacterial species.

DNA Primers↗

Evaluation of the LiPA MYCOBACTERIA assay for identification of mycobacterial species from BACTEC 12B bottles.

The LiPA MYCOBACTERIA (Innogenetics NV, Ghent, Belgium) assay was used to identify mycobacterial isolates using culture fluid from positive BACTEC 12B bottles. The LiPA method involves reverse hybridization of a biotinylated mycobacterial PCR fragment, a 16 to 23S rRNA spacer region, to oligonucleotide probes arranged in lines on a membrane strip, with detection via biotin-streptavidin coupling by a colorimetric system. This system identifies Mycobacterium species and differentiates M. tuberculosis complex, M. avium-M. intracellulare complex, and the following mycobacterial species: M. avium, M. intracellulare, M. kansasii, M. chelonae group, M. gordonae, M. xenopi, and M. scrofulaceum. The mycobacteria were identified in the laboratory by a series of tests, including the Roche AMPLICOR Mycobacterium tuberculosis (MTB) test, the Gen-Probe ACCUPROBE, and a PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the 65-kDa heat shock protein gene. The LiPA MYCOBACTERIA assay detected 60 mycobacterium isolates from 59 patients. There was complete agreement between LiPA and the laboratory identification tests for 26 M. tuberculosis complex, 9 M. avium, 3 M. intracellulare complex, 3 M. kansasii, 4 M. gordonae, and 5 M. chelonae group (all were M. abscessus) isolates. Three patient samples were LiPA positive for M. avium-M. intracellulare complex, and all were identified as M. intracellulare by the PCR-RFLP analysis. Seven additional mycobacterial species were LiPA positive for Mycobacterium spp. (six were M. fortuitum, and one was M. szulgai). The LiPA MYCOBACTERIA assay was easy to perform, and the interpretation of the positive bands was clear-cut. Following PCR amplification and gel electrophoresis, the LiPA assay was completed within 3 h.

Bacterial Typing Techniques↗

Disseminated miliary tuberculosis of the skin in patients with AIDS: report of four cases.

We present clinical, bacteriologic, and pathological findings for four patients with AIDS and cutaneous miliary tuberculosis. All patients had generalized tuberculosis with hematogenous dissemination to multiple organs including the skin. Microscopic examination of the skin lesions revealed ill-formed or no granulomata, extensive necrosis, and numerous acid-fast bacilli. Mycobacterium tuberculosis was detected in the skin lesions by cultures for three patients and by polymerase chain reaction for one. Three of the isolates were resistant to at least isoniazid and rifampin, and one was susceptible to these drugs. The outcome was rapidly fatal for the three patients with multidrug-resistant tuberculosis. This report draws attention to the reappearance of a once-rare manifestation of disseminated tuberculosis which, in the setting of advanced human immunodeficiency virus disease, may offer the first indication of infection with multidrug-resistant M. tuberculosis and a poor prognosis.

Acquired Immunodeficiency Syndrome↗

Human T lymphocyte subpopulation and NK cell alterations in persons exposed to cocaine.

Immunophenotypic changes in peripheral blood mononuclear cells were analyzed by flow cytometry in several patient groups positive for cocaine in their urine. Single- and dual-color immunofluorescence staining was performed to examine total numbers of NK, T, and B cells, as well as the coexpression of surface molecules on T cells associated with memory function, helper/inducer capacity, and activation status. In addition, levels of several serum proteins (including immunoglobulins) and other demographic variables were evaluated. Our results show that cocaine-intoxicated patients display reductions in the total percentage of CD4+ T cells and increases in the number of NK cells. Dramatic shifts within certain T cell subpopulations were also observed. In particular, there appeared to be a preferential stimulation of "activated" T cells as indicated by increased levels of class II+ CD4 and CD8 T cells and IL2r+ CD4 T cells. "Memory" CD8+ T cell subpopulations (i.e., CD45RO+) were reduced in the cocaine-positive patients, whereas CD45R+/CD8+ T cells were accordingly increased in the same individuals. In some cases, direct correlation could be established between certain T cell percentages and cocaine levels. None of the serum protein levels measured appeared to be influenced by cocaine. These findings demonstrate that cocaine utilization is associated with variations in levels of certain T cell subpopulations and other immune cells. This may represent a disruption of particular immunologic cell networks which could ultimately influence host resistance to infection and malignancy.

Acute-Phase Proteins↗

The antimicrobial susceptibility patterns of the Bacteroides fragilis group in the United States, 1987.

A nationwide survey to monitor the susceptibility of the Bacteroides fragilis group, which began in 1981, was continued during 1987. In addition to the eleven drugs evaluated in 1986, sulbactam, a potent beta-lactamase inhibitor, was tested alone and in combination with ampicillin and cefoperazone. Imipenem, ampicillin/sulbactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid were the most active newer drugs tested, with less than 1% resistance rates. Chloramphenicol, metronidazole and clindamycin also had excellent activity with resistance rates of 0%, 0%, and 3% respectively. Resistance rates to cefoxitin remained stable at 8%. Ceftizoxime and cefotetan had resistance rates of 26% and 29%, respectively. Rates of resistance varied among different institutions and between the various species.

Anti-Bacterial Agents↗

Comparative activities of newer beta-lactam agents against members of the Bacteroides fragilis group.

A nationwide susceptibility survey of 557 isolates of the Bacteroides fragilis group was continued in 1986. The most active beta-lactam drugs were imipenem and ticarcillin-clavulanic acid, which had 0.2 and 1.7% resistance, respectively. The rank order of activity of beta-lactam drugs was imipenem, ticarcillin-clavulanic acid, cefoxitin, piperacillin, moxalactam, ceftizoxime, cefotetan, cefotaxime, cefoperazone, and ceftazadime.

Anti-Bacterial Agents↗

Detection of Epstein-Barr virus genomes in normal human lacrimal glands.

Epstein-Barr virus (EBV) has been implicated in several ocular diseases; however, detection of the EBV genome in ocular tissues has not been documented. We report the detection of amplified EBV genomic sequences in 11 of 26 normal lacrimal gland DNA samples by using the polymerase chain reaction. Serum was available for 19 of the lacrimal gland donors. All 19 were EBV seropositive, although of the 19 lacrimal gland-seropositive patients, EBV sequences were detected in only 10 of the samples. Further, amplified EBV sequences were not detected in circulating lymphocyte DNA from normal seropositive volunteers, most likely because of the low frequency of circulating EBV-infected B cells. Amplification of EBV from cadaver lacrimal gland DNA was possible with minute quantities of DNA, whereas peripheral blood mononuclear cell DNA from normal volunteers did not amplify EBV sequences. Interestingly, the peripheral blood mononuclear cell polymerase chain reactions contained approximately 100 times more DNA than the lacrimal gland polymerase chain reactions. We conclude that the lacrimal gland may be a site for EBV persistence and that positive EBV serology is not an indicator of which individuals may have EBV harbored within their lacrimal glands.

Base Sequence↗

Detection of herpes viral genomes in normal and diseased corneal epithelium.

Herpetic ocular disease is one of the major causes of corneal blindness. Clinical diagnosis of corneal disease is based principally on corneal appearance. However, abnormal morphology of the corneal epithelium (CE) is not an indicator for the presence of a herpes virus. Further, it has not been established if herpes viruses are present in normal corneal epithelial tissue. In these studies, the polymerase chain reaction was used to evaluate normal and diseased corneal epithelium for the presence of herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) genomic sequences. Thirty-two normal corneal epithelium specimens obtained from cadavers shortly after death were analyzed for HSV-1, EBV and CMV genomic sequences. Three of the 32 normal CE specimens were positive for amplified EBV DNA, 1 was positive for HSV-1 DNA, and none was positive for CMV DNA. We also tested eight herpetic dendritic lesions of which 3 were HSV-1 culture and PCR positive. The remaining five dendritic lesions were HSV-1 culture and PCR negative. Since these lesions were not evaluated for other herpesviruses, the etiology of these dendritic lesions is unknown. Six corneal epithelium samples from HIV-infected donors were negative for EBV, CMV and HSV-1 amplified sequences. Positive EBV, CMV and HSV-1 serology on all normal donors and on donors with clinically apparent disease did not correlate with positive PCR results. The results of these studies suggest that EBV and HSV-1 DNA can be amplified from a small percentage of apparently normal corneal epithelium.

Adult↗

Susceptibility of the Bacteroides fragilis group in the United States: analysis by site of isolation.

An ongoing survey of the susceptibility of the Bacteroides fragilis group of bacteria was continued at New England Medical Center in 1984 and 1985. A total of 1,229 strains were obtained from eight centers in the United States. These results were compared with those for 1,847 isolates tested in 1981 through 1983. The most active beta-lactam drugs were imipenem and ticarcillin-clavulanic acid (Timentin), which had a less than 1% resistance rate. No metronidazole- or chloramphenicol-resistant isolates were found during the 5 years of the study. Isolates obtained from blood, perinatal, and bone sites of infection were more resistant to a variety of antimicrobial agents. Susceptibility patterns of the members of the B. fragilis group varied at the eight hospitals and among species. These data indicate the need for determining the susceptibility patterns for the B. fragilis group of organisms at each hospital.

Anti-Bacterial Agents↗

Tuberculosis and nontuberculous mycobacteriosis in patients with AIDS.

Thirty-six patients with AIDS and culture-proven nontuberculous mycobacteriosis were compared to 20 patients with acquired immunodeficiency syndrome (AIDS) and tuberculosis with regard to clinical signs, symptoms, and diagnostic methods. Patients with nontuberculous mycobacteriosis were more often younger and homosexuals, while patients with tuberculosis were usually Haitian-American or users of intravenous drugs. A majority of patients with tuberculosis presented with fever and weight loss. These symptoms were seen in approximately 50 percent of the patients with nontuberculous mycobacteriosis. A distinct syndrome of dyspnea, chills, hemoptysis, and chest pain was seen in a significant minority of patients with nontuberculous mycobacteriosis. Lymphadenopathy was seen almost exclusively in patients with tuberculosis. Pulmonary sources (expectorated sputum or bronchoscopy specimens) were the most common source of diagnosis in both groups. Patients in both groups in whom the diagnosis was obtained from pulmonary sources frequently had negative chest x-ray films on presentation. Cavitary disease was absent from both groups.

Acquired Immunodeficiency Syndrome↗

Nationwide study of the susceptibility of the Bacteroides fragilis group in the United States.

A nationwide susceptibility survey of the Bacteroides fragilis group was continued at New England Medical Center in 1983. A total of 555 strains were obtained from eight centers in the United States. In addition to the nine antimicrobial agents studied in the two previous years, three other agents were added to the evaluation: cefamandole, cefuroxime, and cefonicid. The results for the strains tested with the original nine drugs in 1983 were compared with those for 1,292 isolates tested in 1981 and 1982. The most active beta-lactam drug was piperacillin, which had an 8% resistance rate. Cefoxitin resistance increased from 10% in 1982 to 16% in 1983. High rates of resistance to cefotaxime, cefoperazone, cefamandole, cefonicid, and cefuroxime were encountered. No metronidazole- or chloramphenicol-resistant isolates were found during the 3 years of the study. Susceptibility patterns varied at the eight hospitals: the outbreak of cefoxitin resistance reported in 1982 at New England Medical Center remitted, while a high clindamycin resistance rate was documented at one hospital in 1983. These data indicate the need for determining the susceptibility patterns for the B. fragilis group of organisms at each hospital.

Anti-Bacterial Agents↗

Antimicrobial susceptibilities of 1,292 isolates of the Bacteroides fragilis group in the United States: comparison of 1981 with 1982.

A susceptibility survey of 537 strains of the Bacteroides fragilis group from eight centers in the United States was continued at the Tufts New England Medical Center in 1982. The results were compared with those of 755 organisms analyzed in 1981. Nine antimicrobial agents were tested by an agar dilution method. The respective percentages of resistance for 1981 and 1982 were as follows (%): cefoxitin, 8 and 10; moxalactam, 22 and 12; cefotaxime, 54 and 48; cefoperazone, 57 and 54; piperacillin, 12 and 7; clindamycin, 6 and 3; metronidazole, 0 and 0; chloramphenicol, 0 and 0; and tetracycline, 63 and 59. Regional differences in resistance rates were found. Declines in resistance to moxalactam, piperacillin, and clindamycin were noted at the participating hospitals. An outbreak of cefoxitin resistance was noted at the Tufts New England Medical Center, where the rate increased from 14 to 30%. The various species of the B. fragilis group had differing patterns of resistance; B. fragilis was the most susceptible species. Significant cross resistance among the beta-lactam agents was found. These data indicate the need to determine the susceptibility patterns of the B. fragilis group organisms within each hospital.

Anti-Bacterial Agents↗

Surveillance study of pediatric patients receiving respiratory therapy, using the Bain circuit system.

The Bain circuit, which has been used previously for anesthesia, was adopted for long-term mechanical ventilation for infants and children in a pediatric intensive care unit. When this ventilation system is used, humidifier temperatures must be kept at temperatures significantly lower than the recommended 50 degrees C to avoid excessive airway temperatures and thermal injury. Routine infection control measures such as daily changing of respiratory therapy equipment and the use of sterile water in Cascade humidifiers were enforced. It was demonstrated that the use of the Bain circuit with a Cascade humidifier kept at a temperature of 36.9 degrees +/- 1.9 degrees C was not associated with nosocomial infection of the lower respiratory tract.

Acinetobacter↗