Clozapine for drug-induced psychosis in Parkinson's disease.
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Biomedical subjects
Publications and source records attributed to T M Brown.
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We surveyed human immunodeficiency virus (HIV) subtype distribution from peripheral blood mononuclear cells (PBMCs) collected in 1995 from 24 HIV-1-infected Kenyan residents (specimens from predominantly male truck drivers and female sex workers near Mombasa and Nairobi). Processed lysates from the PBMC samples were used for env amplification, directly sequenced, and analyzed by phylogenetic analysis. Envelope amplification products were also used for analysis in a polymerase chain reaction (PCR)-based assay, called the combinatorial melting assay (COMA). Results of the two tests were compared for assignment of subtype for this Kenyan cohort. The COMA, a PCR capture technique with colorimetric signal detection, was used with HIV reference subtype strains as well as regional (East Africa) HIV strains for subtype identification. Performance of the COMA was at 100% concordance (24 of 24) as compared with DNA sequencing analysis. Phylogenetic analysis showed 17 isolates to be subtype A, 3 subtype D, and 4 subtype C viruses. This may represent an increase in subtype C presence in Kenya compared with previously documented reports. The COMA can offer advantages for rapid HIV-1 subtype screening of large populations, with the use of previously identified regional strains to enhance the identification of local strains. When more detailed genetic information is desired, DNA sequencing and analysis may be required.
BACKGROUND: Using a disease specific questionnaire, the CLAU-S, we undertook a double blind, placebo controlled study in patients with intermittent claudication to determine whether the increase in the pain-free walking distance, previously demonstrated with naftidrofuryl, is reflected as an improvement in the patients' quality of life. PATIENTS AND METHODS: 287 patients, with stable intermittent claudication for at least 3 months were entered into the study. Following an initial one month placebo run-in, patients were randomised to either naftidrofuryl, at a dosage of 200 mg three times daily, or matching placebo, for 6 months. All patients completed the self-administered CLAU-S questionnaire which is divided into 6 dimensions, before the start of treatment, at 3 and 6 months. Statistical analysis was undertaken on an intention-to-treat (ITT) basis which included all patients know to have taken at least one dose of the drug and to have provided key data on at least one occasion after baseline. For each of the CLAU-S dimensions the two groups were compared with respect to difference between the initial and final values. RESULTS: 255 patients (133 naftidrofuryl, 122 placebo) were eligible for the ITT analysis. Significant improvements, in favour of the active medication, were seen for the dimensions "daily living", "pain", "disease specific anxiety" and "mood". A multivariate analysis of covariance, which took into account such factors as initial score, age and sex confirmed the global superiority of naftidrofuryl (p = 0.004). CONCLUSIONS: In this placebo controlled study, using a disease specific questionnaire, naftidrofuryl has been shown to significantly improve several aspects of the quality of life of patients with intermittent claudication.
A circular configuration of genomic DNA was observed in ascoviruses isolated from two species of insects of the family Noctuidae [fall armyworm (Spodoptera frugiperda) and cotton bollworm (Helicoverpa zea)] using restriction endonuclease (REN) digestion, conventional gel electrophoresis, pulsed-field gel electrophoresis and Southern hybridization analysis. This circular configuration of ascovirus genomic DNA was established based on the difference between linear and circular DNA in the numbers of fragments resolved on agarose gel electrophoresis after single and double REN digestion. Genomic DNA of ascoviruses was found to be sheared after purification.
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Genetic resistance to pyrethroid insecticides involves nervous system insensitivity linked to regulatory and structural genes of voltage-sensitive sodium channels. We examined the properties and relative density of sodium channels in central neurons of susceptible and pyrethroid-resistant (Pyr-R) insects that were homozygous for the amino acid substitution V421M in the I-S6 transmembrane segment. Pyr-R sodium channels show approximately 21-fold lower sensitivity to the synthetic pyrethroid permethrin and a approximately 2-fold increased sensitivity to the alpha-scorpion toxin LqhalphaIT. Pyr-R channels also exhibit altered gating properties, including a approximately 13 mV positive shift in voltage-dependent activation and approximately 7 mV positive shift in steady-state inactivation. Consistent with these changes in gating behavior, Pyr-R central neurons are less excitable, as evidenced by an approximately 11 mV elevation of action potential threshold. No differences in sodium channel density are evident. The altered properties of Pyr-R sodium channels provide a plausible molecular basis for nervous system insensitivity associated with pyrethroid resistance.
OBJECTIVE: To evaluate the sensitivity and specificity of an RNA detection assay for diagnosing perinatal HIV infection. METHODS: Plasma and serum specimens taken during the first 3 months of life from HIV-infected and uninfected children enrolled in a cohort study were assayed for HIV RNA using the qualitative nucleic acid sequence-based amplification (NASBA) kit. Sensitivity, specificity, and predictive values were calculated. NASBA results from infected children were compared with DNA PCR results from the same blood samples. Autoantibody patterns of suspected false-positive specimens were compared with those of subsequent specimens from the same child to exclude specimen labelling errors. RESULTS: Amongst 131 specimens from 105 HIV-infected children, the sensitivity of the qualitative NASBA assay was 13 out of 34 [38%; 95% confidence interval (CI), 22-56] at < 7 days, 56 out of 58 (97%; 95% CI, 88-100) at 7-41 days, and 37 out of 39 (95%; 95% CI, 83-99) at 42-93 days of life. Of 252 specimens from 206 uninfected children, six tested positive and one tested indeterminate by NASBA. Four of these positive specimens had discordant autoantibody patterns suggesting mislabelling; excluding these, the test specificity was 245 out of 248 (99%; 95% CI, 97-100). Amongst 128 paired specimens from infected children, NASBA results were more often positive than those from DNA PCR (103 versus 92; P=0.01). Amongst infants with specimens drawn in the first week of life, the proportion born after > 4 h of membrane rupture was greater amongst those testing negative (81%) than those testing positive (46%; P=0.05). CONCLUSIONS: The qualitative NASBA RNA assay is highly specific and more sensitive than DNA PCR. Qualitative RNA assays may be useful for diagnosing and excluding perinatal HIV infection in children after the first week of life for such purposes as initiating antiretroviral therapy and other treatment, resolving parental uncertainty, determining timing of transmission, and providing endpoints for intervention trials.
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Among a cohort of 152 infants perinatally infected with human immunodeficiency virus type 1, and their mothers, we correlated infant outcome with material CD4+ lymphocyte count and the presence of maternal acquired immunodeficiency syndrome near delivery. In a subset of 50 mother-infant pairs, we also correlated infant outcome with maternal quantitative viral burden as measured by the nucleic acid sequence based amplification system. We found that low maternal CD4+ cell count and high viral burden were associated with decreased time to category C disease or death in infants infected with human immunodeficiency virus type 1. In a multivariate analysis, high maternal viral load and maternal acquired immunodeficiency syndrome were independently associated with shorter time to category C disease or death in infants with human immunodeficiency virus type 1 infection. High viral load in pregnant women, independent of the presence of advanced maternal disease, appears to increase the risk of rapidly progressive disease in their infected offspring.
Early diagnosis of perinatally transmitted human immunodeficiency virus type 1 (HIV) infection can guide early interventions. HIV coculture and DNA polymerase chain reaction (DNA-PCR) detect few HIV-infected infants at birth and 90%-100% by age 3 months. Because extracellular HIV RNA may appear soon after infection, a plasma HIV RNA assay was compared with DNA-PCR for early detection of perinatally infected infants. Blood-draw specimens (108) obtained at the same time from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants <28 days of age (binomial test, P = .001). Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative. These results suggest that plasma HIV RNA was detectable earlier and more reliably than HIV DNA in perinatal infection.
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Twenty-five veterans suffering from combat-related posttraumatic stress disorder were studied for 1-4 nights with all-night polysomnography. All subjects had sleep complaints. Analysis reveals that nineteen (76%) of the patients were found to have clinically significant periodic limb movements of sleep (PLMs) by the second night of study. PLMs are associated with sleep complaints in normals. For this reason the common assumption that sleep complaints in posttraumatic stress disorder are related only to the psychiatric disorder itself are challenged.
Resistance to methyl parathion insecticide has evolved in the tobacco budworm, Heliothis virescens, and several biochemical mechanisms have been identified in various strains. Reduced sensitivity of acetylcholinesterase to inhibition by methyl paraoxon, the active metabolite of the insecticide, is controlled by a single autosomal locus, AceIn. We report that AceIn is genetically linked to methyl parathion resistance, which is expressed as a dominant gene. Methyl parathion-resistant and -susceptible strains were intercrossed and the resulting mixed colony was heterozygous at AceIn. Pair matings from the mixed colony were chosen, on the basis of AceIn genotype only, to establish strains Ace-S and Ace-R, homozygous for AceInSS and AceInRR, respectively. The Ace-R strain was 15.9-fold resistant compared to AceInSS, while hybrid progeny expressed 24.6-fold resistance, demonstrating dominant inheritance of resistance. When progeny of the backcross (Ace-S x Ace-R) to Ace-S were exposed to a discriminating dose of methyl parathion, 24.5% survived as predicted by the model of a single resistance gene. Survivors displayed only the AceInRS genotype, demonstrating a linkage disequilibrium which was highly significant. Assuming that no other resistance genes are linked closely to AceIn, it would appear that AceIn is a powerful gene for resistance, conferring a resistance proportional to the slower rate of inhibition in the resistant enzyme. The contribution of AceIn to resistance relative to detoxicative genes and the possible interaction of resistance genes are discussed.
Two hundred and forty new medical inpatients received Alcohol Use Disorders Identification Test (AUDIT), CAGE and brief Michigan Alcoholism Screening Test (brief MAST) questionnaires. Sensitivities when identifying weekly drinkers of > 14 units (women) or > 21 units (men) were 93, 79 and 35%, respectively (P < 0.001). Sensitivities to > 21 units (women) or > 28 units (men were 100%, 94% and 47%. Routine screening of medical admissions with the AUDIT (cut-off score 8) is recommended.
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