Kaiser Northern California considering out-of-network contracts.
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Biomedical subjects
Publications and source records attributed to D McGuire.
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We compared the pharmacokinetic and motor responses of Sinemet and Atamet (generic carbidopa/levodopa) in patients with Parkinson's disease. Thirty Parkinson's disease patients (10 previously untreated, 10 with early disease, and 10 with motor fluctuations/dyskinesia) participated in a single-dose double-blind study. Following administration of an equivalent oral dose of Sinemet and Atamet on two separate days, we compared the peak plasma concentration, time to peak plasma concentration, area under the curve, total motor score, tapping score, and walking time. The mean time to peak plasma concentrations was 49 min with Sinemet and 47 min with Atamet, the mean peak plasma concentration was 1,273 ng/ml with Sinemet and 1,153 ng/ml with Atamet, and the mean area under the curve was 2,295 micrograms/ml/h with Sinemet and 2,330 micrograms/ml/h with Atamet. Similarly, there was no significant difference between total motor score, tapping score, or walking time. In this single-dose study, there were no significant differences in pharmacokinetic and motor responses between Sinemet and Atamet.
OBJECTIVE: To determine whether or not soluble factors produced by peripheral blood mononuclear cells (PBMC) can predict AIDS dementia. DESIGN AND METHODS: PBMC were isolated from individuals with and without AIDS dementia complex (ADC) to determine if the levels of cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-6, or the production of a neurotoxic substance, were significantly different. PBMC were studied after determining that the numbers of monocyte-derived macrophages isolated by adherence were highly variable from patients with ADC compared with individuals without ADC. We prospectively studied 16 AIDS dementia patients, 13 healthy HIV-seropositive individuals, and eight sero-negative controls. Supernatants from PBMC were assayed for TNF-alpha, IL-6 and alone for neurotoxicity on human neural cells in vitro. RESULTS: We observed a trend towards worse cognitive and motor performance in patients suffering from ADC but who had no opportunistic infections ('pure dementia'; n = 8). Levels of PBMC IL-6 were significantly higher in 'pure dementia' patients. There was a trend towards lower levels of PBMC TNF-alpha in the group of patients who had both dementia and opportunistic infections compared with "pure dementia' patients. Supernatant from PBMC of ADC patients was significantly more neurotoxic than that from healthy HIV-seropositive individuals. CONCLUSIONS: Macrophage isolation from PBMC of patients with ADC was altered. Soluble factors produced from PBMC were significantly more neurotoxic than soluble factors from PBMC of healthy HIV-seropositive individuals. PBMC production of TNF-alpha and IL-6 was not a significant predictor of ADC.
We examined the effects of supplemental standard carbidopa/levodopa (Std-L) on early morning akinesia in patients with Parkinson's disease (PD) who were being treated with sustained-release carbidopa/levodopa (L-CR). We compared plasma dopa levels and clinical response in 15 PD patients after a dose of Std-L and L-CR (2 hours later) and after a dose of L-CR and placebo in a double-blind, placebo-controlled, crossover study. Plasma dopa levels, total motor score, walking time, and finger tapping time were assessed every 15 minutes for the first 2 hours and then every 30 minutes for the next 3 hours. The time of onset in clinical benefit was significantly earlier with Std-L (47 minutes, range 15 to 75 minutes) as the first dose as compared with L-CR (58 minutes, range 30 to 105 minutes). Similarly, there was a significant difference in the peak plasma dopa levels (Cmax) and the time to reach peak plasma dopa levels (Tmax) with administration of Std-L (Tmax 36 minutes; Cmax 1,501 micrograms/ml) as compared with L-CR (Tmax 111 minutes, Cmax 1,260 micrograms/ml). There was no significant difference in dyskinesias between the two treatment arms. An initial morning dose of Std-L alleviates the problem of delayed-onset clinical response that commonly occurs with L-CR.
The Tufts Quantitative Neuromuscular Exam (TQNE) is a standardized tool for measuring muscle strength and pulmonary function in patients with amyotrophic lateral sclerosis (ALS). We describe the relationship of TQNE scores to functional disability and health-related quality of life as measured by the Sickness Impact Profile (SIP) in 524 ALS patients. There was a significant relationship (p < 0.0001) between TQNE and SIP scores, both in cross section and over time. TQNE scores strongly relate to ALS patients' quality of life and ability to perform activities of daily living.
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Progressive multifocal leukoencephalopathy (PML) is a lytic infection of oligodendrocytes by the human papovavirus JC. Patients with defects in cell-mediated immunity are at risk for active disease: a usually lethal demyelination of the brain. PML develops in at least 4% of patients with the acquired immunodeficiency syndrome (AIDS). Definitive diagnosis currently requires brain biopsy. Previous attempts to detect JC virus DNA by polymerase chain reaction in cerebrospinal fluid of PML patients, particularly those with human immunodeficiency virus type 1 (HIV-1) infection, have been of low sensitivity. In the present study, cerebrospinal fluid was assayed by polymerase chain reaction from 26 HIV-1-positive patients with PML, 114 HIV-1-positive control subjects, and 16 control subjects who were HIV-1 negative or were without risk factors for HIV disease. Polymerase chain reaction conditions were optimized to detect a single copy of viral DNA in 50 microliters of cerebrospinal fluid. Specificity of the polymerase chain reaction product was confirmed by size on gel electrophoresis and Southern blot hybridization. JC virus DNA was detected in 24 of 26 samples from patients with PML: 8 of 8 with tissue diagnosis and 16 of 18 with strong clinical and magnetic resonance imaging evidence of PML. Among control subjects, 11 of 130 samples were positive for JC virus: 10 of 114 samples from HIV-infected patients and one from an HIV-negative patient with risk factors for PML and an unexplained hemiparesis. Overall sensitivity was 92% (24/26); specificity was, at minimum, 92% (119/130). Treatments for PML are now in clinical trials.(ABSTRACT TRUNCATED AT 250 WORDS)
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PURPOSE: This study was designed to describe the cerebrospinal fluid (CSF) findings and neurologic diagnoses observed in human immunodeficiency virus (HIV)-infected adults undergoing diagnostic lumbar puncture (LP) and to correlate the results of LP with indications and CD4 counts. DESIGN: Retrospective cross-sectional chart review study. SETTING: University hospital clinic for patients with HIV infection. PATIENTS: All patients of the University of California, San Francisco (UCSF) AIDS Clinic who underwent LP between mid-1987 and mid-1990 for headache, fever, altered mental status, or a combination of these indications. Sixty-seven percent had an AIDS diagnosis at the time of LP; the median CD4 count was 0.091 x 10(9)/L. RESULTS: A total of 138 LPs was analyzed. Elevation of CSF protein and leukocytes occurred in 33% and 27% of specimens, respectively. Seventy-two new neurologic diagnoses were established in 67 patients, but only 30 diagnoses were the result of CSF analysis. Of these 30 diagnoses, 18 were of aseptic meningitis attributed to HIV. None of the 12 treatable diagnoses established by LP occurred in patients known to have a CD4 count of 0.200 x 10(9)/L or greater. Patients undergoing LP because of headache had a lower incidence of new diagnoses than those with altered mental status (35% versus 72%), but LP revealed a higher proportion of diagnoses in the group with headache. CONCLUSIONS: CSF abnormalities were common at all stages of disease. LP was diagnostic in 22% of cases, but fewer than half of the diagnoses were of treatable secondary complications. Patients with a CD4 count higher than 0.200 x 10(9) have a very low incidence of opportunistic complications. The relatively low yield of LP in patients with altered mental status suggests that other testing modalities should be used prior to LP.
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The mechanism for AIDS dementia may involve the production of toxic cytokines. Since macrophage/microglia are the infected cells in the brain, we were interested in the production of some of the same cytokines by HIV-infected macrophages from patients with AIDS dementia. HIV-infected macrophages from 11 patients with AIDS dementia were cultured and evaluated for p24, cytomegalovirus (CMV) DNA, and the production of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF alpha) and other neurotoxic factors. The percentage of HIV macrophage infectivity did not correlate with the severity of dementia nor did the presence of CMV. The production of IL-6 and an unidentified neurotoxin did not correlate with HIV macrophage infectivity suggesting that these soluble factors are strain specific. Production of TNF alpha by HIV-infected macrophages was relatively low (< 1-35 pg/ml) and may not be a significant factor in toxicity.
In an effort to better support the adults with Down syndrome that it serves, parents from the National Association for Down Syndrome, a parent organization, worked with staff members from The Family Study and Service Program of the University Affiliated Program for Developmental Disabilities of the University of Illinois and the Department of Family Practice of Lutheran General Hospital to develop a clinic for adults with Down syndrome. The clinic was developed to provide comprehensive health care with an emphasis on preventative services. The multidisciplinary approach of the clinic has proved to be effective in the management of a variety of patient care needs. The most common health problems found were discussed.
A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis.
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