Biomedical subjects
Publications and source records attributed to Bruce A Cohen.
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Chronic meningitis is a syndrome commonly defined by the presence of continuously persistent meningeal inflammation for at least 4 weeks. Presenting neurologic features are often nonspecific, and the list of differential diagnoses is broad. Despite the development of modern molecular diagnostic methods, establishing a specific cause may challenge the acumen of the treating neurologist with clues to the diagnosis residing outside the nervous system and requiring focused investigation. This review discusses selected etiologies illustrating issues in diagnosis and etiologic categories to be considered in the evaluation of this challenging syndrome.
Diffusion tensor imaging (DTI) was used to derive in vivo tissue status measurements of subcortical brain regions that are vulnerable to injury in human immunodeficiency virus (HIV)-infected patients. Quantitative measurements, including the mean diffusivity (MD) and fractional anisotropy (FA), were determined in lateralized basal ganglia (caudate and putamen) and centrum semiovale in 11 well-characterized HIV patients and in 11 control subjects. DTI measurements were examined for patterns of relationship with markers of clinical and cognitive progression. DTI measures acquired in subcortical regions were significantly correlated with loss of function in specific cognitive domains. Significant relationships were identified between measures for putamen and verbal memory (MD), visual memory (FA), working memory (FA), and overall cognitive impairment (MD). Measures for caudate (FA) were significantly correlated with visual memory. Measures for centrum semiovale were significantly correlated with visual memory deficits (MD) and visuoconstruction (FA). Relationships between anisotropy measures and anemia (basal ganglia) and CD4 counts (centrum semiovale) were also observed. Findings from this investigation indicate that DTI is a sensitive tool for correlating neuroanatomic pathologic features with specific cognitive deficits in patients with HIV infection.
Treatment of patients with mitoxantrone for worsening multiple sclerosis (MS) requires careful monitoring for possible adverse events. Common side effects that are minor and easily managed include transient leukopenia and elevated liver enzymes, nausea, alopecia, bluish discoloration of urine, and urinary tract infections. Amenorrhea, severe infection, cardiac toxicity, and toxic leukemias are more serious adverse events associated with mitoxantrone treatment but occur infrequently. The potential for clinically significant heart failure is low and is dose-related. Subclinical reductions in left ventricular ejection fraction may occur with serial doses, underscoring the importance of careful monitoring before initiating and during treatment. The risk for chronic cardiomyopathy limits the approved cumulative dose of mitoxantrone for treatment of MS to 140 mg/m2. Dexrazoxane has a cardioprotective effect when used with anthracycline in the treatment of patients with neoplasms. Studies under way address whether concomitant administration of dexrazoxane with mitoxantrone might decrease the risk for cardiac toxicity in MS patients and perhaps increase the allowable cumulative dose of mitoxantrone. A phase IV clinical study of mitoxantrone (RENEW) is in progress to assess the long-term safety and tolerability of treatment. Careful laboratory and cardiac monitoring can reduce the possibility of adverse events and enhance patient safety.
Clinicians and researchers who use neuropsychological tests to track functioning over time are in need of a method to correct for the effects of practice. Drawing from a large database of healthy, male subjects, we present data that can be used to calculate predicted retest scores for eight widely used neuropsychological instruments either via simple regression or reliable change index (RCI) methods. These methods are useful for individuals assessed across a wide time interval, 4-24 months. Limitations are discussed regarding the applicability of the data. Those with a need to factor out the effects of practice, test-retest reliability and other statistical confounds will find the information within this article useful.
BACKGROUND AND PURPOSE: Quantitative MR imaging strategies may have considerable potential for in vivo assessment of neuropathologic changes associated with HIV. This investigation evaluated the prognostic significance of whole brain histogram-derived diffusion tensor imaging indices with respect to severity of cognitive impairment and measures of clinical status in cases of HIV. METHODS: Quantitative indices derived with diffusion tensor imaging, including whole brain fractional anisotropy and the apparent diffusion coefficient, were compared for six patients with HIV and eight control volunteers. Relationships between whole brain indices and specific measures of dementia severity and clinical status were examined. RESULTS: Whole brain fractional anisotropy was reduced in patients with HIV and was significantly associated with severity of dementia, as indicated by several widely used clinical and functional status measures. Summary fractional anisotropy measures were more prognostic of dementia status than were apparent diffusion coefficient measures. CONCLUSION: Findings from this investigation support the use of diffusion tensor imaging for noninvasive MR imaging measurement of neuropathologic changes in studies of HIV-associated cognitive impairment.
There were 21 patients with rapidly progressive multiple sclerosis (MS) treated on a phase 1/2 study of intense immune suppressive therapy and autologous hematopoietic stem cell (HSC) support with no 1-year mortality. Following transplantation, one patient had a confirmed acute attack of MS. Neurologic progression defined by the expanded disability status scale (EDSS) did not increase in disability by 1.0 or more steps in any of 9 patients with a pretransplantation EDSS of 6.0 or less. In 8 of 12 patients with high pretransplantation disability scores (EDSS > 6.0), progressive neurologic disability as defined by at least a 1-point increase in the EDSS has occurred and was manifested as gradual neurologic deterioration. There were 2 patients with a pretransplantation EDSS of 7.0 and 8.0 who died from complications of progressive disease at 13 and 18 months following treatment. Our experience suggests that intense immune suppression using a total body irradiation (TBI)-based regimen and hematopoietic stem cell transplantation (HSCT) are not effective for patients with progressive disease and high pretransplantation disability scores. Further studies are necessary to determine the role of intense immune suppressive therapy and HSC support in ambulatory patients with less accumulated disability and more inflammatory disease activity. Specifically, more patients and longer follow-up would be required in patients with an EDSS of 6.0 or less before drawing conclusions on this subgroup.
Despite the use of laboratory markers in estimating HIV prognosis, significant variation in the natural history of HIV-1 infection remains unexplained. Recent studies suggest psychosocial risk factors have important prognostic significance in HIV disease. The objective of the present study was to examine the prognostic influence of age, general intellectual functioning, and emotional distress across the spectrum of HIV disease progression. The study sample was drawn from the Multicenter AIDS Cohort Study (MACS), a 13-year, prospective study of HIV-seropositive men recruited from four study centers across the country. The participants were 1,231 HIV-seropositive MACS participants, followed from baseline (median 8/15/87) to the end of the observation period (12/15/98). HIV disease progression was evaluated with respect to three outcome measures: (1) number of years from baseline testing to the first AIDS defining illness (progression to AIDS), (2) years from baseline to HIV-dementia (progression to dementia), and (3) years from baseline to death (survival). The influence of psychosocial risk factors on outcome measures was evaluated using survival analyses. General intellectual functioning, age, and somatic symptoms of depression, were found to be significant predictors of HIV disease progression and survival. Older age at baseline was associated with a more rapid progression to dementia and death. Lower Shipley IQ estimates were associated with a more rapid disease progression (AIDS and dementia) and shortened survival. Somatic symptoms of depression were associated with shortened survival. In addition, age, IQ, and somatic symptoms of depression, had an additive effect with an increase in the number of risk factors associated with accelerated disease progression and shortened time to death. These findings remained consistent, despite controlling for baseline CD4 and HIV medication use. Psychosocial cofactors are important in understanding HIV disease progression. Methods for estimating HIV prognosis may become more reliable if psychosocial factors are considered. Future research will clarify if psychosocial risk factors reflect central nervous system integrity, brain reserve capacity or mediate morbidity and mortality through social economic status, access to health care and other social correlates.
BACKGROUND: An essential element in planning for long-term space missions is prediction of the medical support required. Medical data for analogous populations serving in isolated and/or contained environments are useful in predicting health risks for astronauts. METHODS: This study evaluated the rates of health events that occurred among a highly screened, healthy military population during periods of isolation using a centralized database of medical encounter records from U.S. Navy submarines. The study population was composed of U.S. Navy officers and enlisted men deployed on 240 submarine patrols between 1 January 1997 and 30 September 2000. RESULTS: A total of 1389 officers and 11,952 enlisted crew members served aboard participating submarines for 215,086 and 1,955,521 person-days at sea, respectively, during the study period. Officers had 214 initial visits to medical staff with 79 re-visits for the same condition during these patrols, while enlisted men had 3345 initial visits and 1549 re-visits. Among officers, the most common category of medical events was respiratory illnesses (primarily upper respiratory infections), followed by injury, musculoskeletal conditions, infectious diseases, symptoms and ill-defined conditions, and skin problems. Among enlisted men, the most common category of medical events was injury, followed by respiratory illnesses (upper respiratory infections), skin problems, symptoms and ill-defined conditions, digestive disorders, infectious conditions, sensory organ problems (ear infections and eye problems), and musculoskeletal conditions. CONCLUSIONS: Potential mission-impacting medical events reported were rare, i.e., among a crew of seven officers, only one medical event would be expected to occur during a 6-mo mission and result in 3/4 d or less of limited or no duty. Among a crew of seven enlisted men, about two medical events would be expected during a 6-mo mission and result in about 1 d of limited or no duty per medical event.
OBJECTIVE: To assess the safety, tolerability and effect of cidofovir for HIV-1 associated progressive multifocal leukoencephalopathy. DESIGN: Prospective, open-label study in nine AIDS Clinical Trials Units. PATIENTS AND METHODS: Twenty-four HIV-1-infected individuals, with neuroimaging and clinical findings consistent with PML, and symptoms for 90 days or less, whose diagnosis was confirmed by the detection of JC virus DNA in the cerebrospinal fluid or brain biopsy, received cidofovir 5 mg/kg intravenously at baseline and 1 week, followed by infusions every 2 weeks with the dose adjusted for renal function. Follow-up continued to 24 weeks. The safety of cidofovir and changes in neurological examination scores between baseline and week 8 were assessed. RESULTS: Seventeen subjects were receiving potent antiretroviral agents. Survival at 12 weeks was 54%. The CD4 cell count at entry was significantly associated with survival (P = 0.02). Five subjects discontinued treatment because of toxicity: a 50% or greater decrease in intraocular pressure in either eye in four, and proteinuria in one. Overall, magnetic resonance imaging abnormalities and neurological examination scores worsened. Only two subjects experienced a 25% or greater improvement in neurological examination scores at week 8, which were significantly better in subjects with HIV-1-RNA levels of 500 copies/ml or less at entry compared with those with HIV-1-RNA levels over 500 copies/ml (P = 0.05). CONCLUSION: Cidofovir did not improve neurological examination scores at week 8. However, such scores were significantly better in subjects who entered with suppressed plasma HIV-1-RNA levels, which could be the result of control of HIV-1 infection itself or cidofovir.