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Biomedical subjects

C M Marra

Publications and source records attributed to C M Marra.

33 records · Page 2Linked to original sources

Hearing loss and antiretroviral therapy in patients infected with HIV-1.

OBJECTIVE: To explore the association between hearing loss and antiretroviral therapy in human immunodeficiency virus type 1 (HIV-1)-infected persons. DESIGN: Case-control study. SETTING: University-based HIV clinic. PARTICIPANTS: Volunteer sample of 99 HIV-infected patients. INTERVENTIONS: Standardized interview focusing on risks for hearing loss, review of clinic pharmacy records, and hearing tests by portable audiometry. MAIN OUTCOME MEASURE: Hearing loss, defined as threshold of more than a 25-dB hearing level at 4000 Hz in 1 or both ears. RESULTS: Hearing loss was common, seen in 29 subjects (29%). It was significantly associated with age and history of ear infection and tended to be more common in subjects prescribed antiretroviral agents. An interaction existed between age and antiretroviral therapy; the association between hearing loss and antiretroviral therapy was significant for subjects aged 35 years or older, but not for subjects younger than 35 years. In subjects aged 35 years or older, this association remained significant using a multivariate model that included those variables found to have the greatest potential for confounding (odds ratio, 4.6; 95% confidence interval, 1.0-20.5; P = .05). CONCLUSIONS: Hearing loss is common among HIV-infected individuals and is associated with antiretroviral therapy in those aged 35 years or older.

Adult↗

Detection of Treponema pallidum by a sensitive reverse transcriptase PCR.

Syphilis is diagnosed by serologic testing or by identification of the causative agent, Treponema pallidum. The bacterium has historically been detected in clinical specimens by dark-field microscopy, immunostaining with polyclonal or monoclonal antibodies, or the rabbit inoculation test (RIT). RIT is considered to be very sensitive and specific, although it is available only in research settings and is not clinically useful due to the length of time required to obtain a result. In recent years, several PCR methods have been developed for the detection of T. pallidum, but none of these has shown a clear advantage in sensitivity over RIT. We have developed a specific and highly sensitive reverse transcriptase PCR (RT-PCR) that targets a 366 bp region of the 16S rRNA of T. pallidum. This RT-PCR can detect a single organism by Southern analysis when whole organisms are diluted and 10(-2) to 10(-3) T. pallidum organisms when RNA equivalents are used to make cDNA. The test was demonstrated to detect 10(-2) T. pallidum RNA equivalents in cerebrospinal fluid. Twenty different strains of T. pallidum, isolated from cerebrospinal fluids, aqueous humor, blood, and chancres, were shown to be detectable by this test. This efficient and sensitive technique could be more useful than existing methods for detecting very low numbers of organisms in clinical samples.

DNA, Bacterial↗

Progressive multifocal leukoencephalopathy presenting as human immunodeficiency virus type 1 (HIV)-associated dementia.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the CNS that usually causes hemiparesis or hemianopsia. Dementia occurs in combination with other neurologic abnormalities. We report a human immunodeficiency virus type 1 (HIV)-infected man whose only manifestation of proven PML was dementia that was clinically indistinguishable from HIV-associated dementia.

AIDS Dementia Complex↗

Diagnosis of neurosyphilis in patients infected with human immunodeficiency virus type 1.

Establishing the diagnosis of neurosyphilis may be particularly difficult in human immunodeficiency virus type 1 (HIV)-infected persons. Polymerase chain reaction (PCR) was used to detect Treponema pallidum DNA in cerebrospinal fluid (CSF) from 81 HIV-infected patients. On the basis of reactive serum and CSF-VDRL tests, 2 patients were diagnosed as having neurosyphilis. T. pallidum DNA was not consistently detected in any sample, even when the CSF-VDRL was reactive. CSF pleocytosis, elevated protein, or depressed glucose concentration was not significantly associated with a history of exposure to or infection with T. pallidum. On the basis of results of routine CSF measurements and T. pallidum PCR results, no evidence was found for undiagnosed neurosyphilis in HIV-infected patients. T. pallidum DNA PCR on CSF did not provide more information than conventional CSF analysis. Further study is needed to determine the utility of this test in the diagnosis and treatment of neurosyphilis.

DNA, Bacterial↗

Neurologic Manifestations of HIV Infection Without AIDS:Follow-UP of a Cohort of Homosexual and Bisexual Men.

To identify neurological abnormalities in HIV infection, 159 HIV-seropositive men without AIDS and 76 seronegative controls underwent standardized general and neurological examinations, lumbar puncture (LP), neuropsychological (NP) assessment, and brain magnetic resonance (MR) imaging. History, physical, and laboratory evaluations were repeated every six months. NP tests (all subjects) and MR imaging (seropositives only) was repeated every 6-12 months; LP (seropositives only) was repeated yearly. Mean follow-up was 24.6 months. Neurological abnormalities, most related to hearing, were seen in 60 (38.2%) of 157 seropositives and 23 (30.3%) of 76 controls at baseline (p = NS). During follow-up, 43 (31.6%) of 136 seropositives had persistent hearing abnormalities compared to 9 (14.1%) of 64 seronegatives (p = 0.008). Seven HIV-seropositives developed peripheral neuropathy; this was more common among those with hearing abnormalities (p = 0.03). HIV-seropositives performed less well on NP tests than controls, but overall performance did not decline. Worsening brain atrophy by MR imaging or cerebrospinal fluid abnormalities are more common in HIV-seropositives than seronegatives and may share a common mechanism with peripheral neuropathy. Further study is needed to determine whether these abnormalities portend more serious neurological disease.

Acquired Immunodeficiency Syndrome↗

Cerebrospinal fluid treponemal antibodies in untreated early syphilis.

OBJECTIVE: Examine prevalence and diagnostic utility of cerebrospinal fluid (CSF) treponemal antibodies in early syphilis. DESIGN: Comparison study. SETTING: Sexually transmitted diseases clinic. PATIENTS: Forty patients with untreated early syphilis who underwent lumbar puncture. Fifteen were human immunodeficiency virus seropositive. MEASUREMENTS: Cerebrospinal fluid cell count, protein, VDRL test, and antibodies to Treponema pallidum by microhemagglutination test for T pallidum (MHA-TP) and fluorescent treponemal antibody absorption test (FTA-ABS); albumin ratio; and IgG index. RESULTS: Cerebrospinal fluid cell count was not available for one sample, and this patient was excluded from analysis. Of 39 patients, eight (21%) had reactive CSF-VDRL (definite neurosyphilis). Eleven (28%) had mildly elevated cell count or protein concentration, but nonreactive CSF-VDRL (possible neurosyphilis). Twenty had normal cell count and protein concentration, and non-reactive CSF-VDRL (normal). Cerebrospinal fluid MHA-TP and CSF FTA-ABS were reactive in all eight with neurosyphilis. Cerebrospinal fluid MHA-TP was reactive in seven (70%) of 10 with possible neurosyphilis and in six (32%) of 19 with normal CSF. Cerebrospinal fluid FTA-ABS was reactive in four (36%) of 11 with possible neurosyphilis and in five (28%) of 18 with normal CSF. A reactive CSF treponemal test was associated with higher mean CSF cell count and reactive CSF-VDRL. CONCLUSION: When criteria to define neurosyphilis depend on cell count or CSF-VDRL reactivity, the sensitivity of CSF treponemal antibodies is high. Nonreactive CSF treponemal tests may help to exclude a diagnosis of neurosyphilis in patients with early syphilis.

Antibodies, Bacterial↗

Neurologic complications of Bartonella henselae infection.

Bartonella henselae can cause cat scratch disease and bacillary angiomatosis, a multisystem disorder seen primarily in patients with the acquired immunodeficiency syndrome. Both of these diseases are associated with neurologic complications, particularly encephalopathy. B. henselae may also cause bacteremia and endocarditis, and has been associated with aseptic meningitis and with dementia in patients also infected with the human immunodeficiency virus. Recent advances in identification of this difficult-to-culture organism will lead to recognition of more neurologic complications.

AIDS Dementia Complex↗

The response of symptomatic neurosyphilis to high-dose intravenous penicillin G in patients with human immunodeficiency virus infection.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. METHODS: Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. RESULTS: In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. CONCLUSIONS: In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

Adult↗

Alterations in the course of experimental syphilis associated with concurrent simian immunodeficiency virus infection.

Case reports suggest that the course of syphilis is altered in patients infected with human immunodeficiency virus (HIV). To investigate this issue, a model of syphilis in rhesus macaques with and without simian immunodeficiency virus (SIV) was developed. After intradermal inoculation with Treponema pallidum, 2 SIV-infected monkeys had persistent ulcerative primary lesions and 1 developed secondary syphilis. Two SIV-uninfected controls developed transient nonulcerative primary lesions. Only the controls showed consistent VDRL antibody responses. In contrast, reciprocal antibody titers to T. pallidum detected by microhemagglutination were higher in SIV-infected animals (greater than or equal to 20,480) than controls (greater than or equal to 1280). All 4 animals developed a full range of T. pallidum antigen-specific antibodies shown by immunoblot and had similar peak lymphocyte proliferative responses to T. pallidum antigens. These results support the contention that retrovirus-induced immunodeficiency delays clearance of T. pallidum from sites of infection and may impair the humoral immune response to syphilis.

Animals↗

Resolution of serum and cerebrospinal fluid abnormalities after treatment of neurosyphilis. Influence of concomitant human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVES: Little is known about resolution of serum and cerebrospinal fluid abnormalities after neurosyphilis treatment, especially in patients infected with human immunodeficiency virus (HIV). GOAL: To examine the time course of resolution of these abnormalities. STUDY DESIGN: Case series of 22 patients with neurosyphilis (13 infected with HIV) with reactive cerebrospinal fluid Venereal Disease Research Laboratory test who underwent at least one lumbar puncture after treatment. RESULTS: Resolution of all serum and cerebrospinal fluid measures was slower in patients infected with HIV. Serum and cerebrospinal fluid abnormalities resolved in most patients not infected with HIV by 30 weeks, and all met Centers for Disease Control and Prevention criteria for cure. One patient infected with HIV failed therapy by Centers for Disease Control and Prevention criteria, and three others had persistent pleocytosis. CONCLUSIONS: HIV-infected patients with neurosyphilis have slower resolution of serum and cerebrospinal fluid abnormalities after therapy. This observation may suggest impaired clearance of Treponema pallidum from the central nervous system.

Antibodies, Bacterial↗