Biomedical subjects
J D Wright
Publications and source records attributed to J D Wright.
Knowledge and experience of young people regarding drug misuse, 1969-94.
OBJECTIVE: To monitor young people's knowledge and experience of illicit drugs between 1969 and 1994 at intervals of five years. DESIGN: The same anonymously completed questionnaire was used throughout. SETTING: Three Wolverhampton secondary schools representing three different socioeconomic groups. SUBJECTS: 392 pupils aged 14 to 15 completed the questionnaire in 1994. Previous sample sizes were 471 in 1969, 523 in 1974, 648 in 1979, 540 in 1984, and 380 in 1989. MAIN OUTCOME MEASURES: Self reported levels of knowledge and experience of illicit drugs. RESULTS: Over 25 years the proportion of pupils who knew someone taking drugs more than quadrupled from 15% (71/471) to 65% (254/392), and the proportion who had been offered drugs increased ninefold from 5% (24) to 45% (175). Both of these proportions more than doubled over the past five years. In 1994 the proportions of pupils mentioning "ecstasy" (methylenedioxymethamphetamine), amphetamines, and crack cocaine increased significantly (P < 0.01) and the proportion mentioning opiates decreased significantly (P < 0.01). "Poppers" (amyl nitrite) were mentioned for the first time. "To feel big, to show off, look grown up" has continued to be the main perceived reason for taking drugs. Television has continued to be the main source of information. CONCLUSIONS: In the past five years in particular young people's exposure to illicit drugs has increased dramatically. Despite more education about drugs, pupil's knowledge remains limited. Social pressures remain the first perceived reason for taking drugs. The media have a responsibility not to glamorise drugs.
Specific binding assay for biotin based on enzyme channelling with direct electron transfer electrochemical detection using horseradish peroxidase.
A model 'homogeneous' format enzyme channelling specific binding assay for biotin based on peroxide-sensitive horseradish peroxidase mediatorless enzyme electrodes is described. The procedure involved the immobilisation of avidin onto the surface of printed carbon horseradish peroxidase (HRP) enzyme electrodes and the competitive binding of biotin and biotinylated glucose oxidase. Upon addition of glucose, hydrogen peroxide was generated via the glucose oxidase label. Direct electron transfer between the electrodes and HRP resulted in the detection of H2O2 by electroenzymic reduction at +50 mV vs Ag/AgCl. The cathodic current response could be measured in the presence of excess biotinylated glucose oxidase by incorporation of catalase in homogeneous solution to scavenge H2O2 generated in the bulk before it diffused to the electrode surface. The assay showed greatest sensitivity over the range of biotin concentrations 0.07 to 2 micrograms ml-1 in the presence of 10 micrograms ml-1 excess biotinylated glucose oxidase in the bulk solution.
Pharmacokinetics of 1-(2-deoxy-2-fluoro-beta-L-arabinofuranosyl)-5-methyluracil (L-FMAU) in rats.
PURPOSE: The objective of this study was to characterize the pharmacokinetics of 1-(2-deoxy-2-fluoro-beta-L-arabinofuranosyl)-5-methyluracil (L-FMAU), a nucleoside analogue with potent activity against the hepatitis B virus and the Epstein-Barr virus, in rats. METHODS: Three doses of L-FMAU were administered intravenously (10, 25, and 50 mg/kg) to rats, and L-FMAU concentrations in plasma and urine were measured by HPLC. Pharmacokinetic parameters were generated by using area-moment analysis. RESULTS: There were no significant differences in the pharmacokinetic parameters between the three doses (alpha < 0.05). Thus, the disposition of L-FMAU was linear over the dosage of 10 to 50 mg/kg. Plasma concentrations of L-FMAU declined rapidly with a terminal phase half-life of 1.33 +/- 0.45 h (mean +/- SD). Total clearance of L-FMAU was moderate, averaging 1.15 +/- 0.28 L/h/kg. The fraction of compound excreted unchanged in urine was 0.59 +/- 0.13. No glucuronide metabolite was found in the urine. The steady-state volume of distribution was 1.12 +/- 0.26 L/kg indicating intracellular distribution of the compound. The fraction of L-FMAU bound to plasma proteins was approximately 15% and was independent of nucleoside concentration. CONCLUSIONS: The pharmacokinetics of L-FMAU in rats were independent of dose over the dosage range of 10 to 50 mg/kg.
Housing dynamics of the homeless: implications for a count.
Housing dynamics of homeless people limit all efforts to count them. Data on 60-day housing histories from a sample of homeless substance abusers in New Orleans show that homeless people spend relatively few nights in locations that would make them potentially countable, no matter how thorough the enumeration procedure.
The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the antimalarial biguanides.
The effects of the CYP2C19 substrates, mephenytoin, methsuximide and mephobarbitone on the metabolism of proguanil and chlorproguanil by human liver microsomes were studied. All of the CYP2C19 substrates significantly inhibited (P < 0.05) the formation of both cycloguanil and chlorcycloguanil from their parent compounds. In the presence of mephenytoin (50 and 100 microM) the extent of proguanil cyclisation was decreased by 66% and 67% whilst the cyclisation of chlorproguanil was decreased by 51% and 70%, respectively. Methsuximide (50 and 100 microM) inhibited cycloguanil formation by 68% and 77% and chlorcycloguanil formation by 43% and 58%, respectively. In the presence of mephobarbitone (50 and 100 microM) the cyclisation of proguanil and chlorproguanil to their active metabolites was reduced by 24% and 42% and 48% and 63%, respectively. In addition, proguanil and chlorproguanil were shown to be mutual competitive inhibitors of metabolism to their triazine metabolites. In the presence of proguanil (50 and 100 microM) the Km value for chlorcycloguanil production was increased by 118% and 200%, respectively, with little change in Vmax. Similarly, chorproguanil (50 microM) increased the Km for the in vitro cyclisation of proguanil by 50% with no alteration in Vmax. These data suggest that both chlorproguanil and proguanil are metabolised in vitro by mephenytoin hydroxylase, CYP2C19.
Complication after the use of a combination of lignocaine and xylazine for epidural anaesthesia in a mare.
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Angioplasty-induced pseudoaneurysm successfully treated with a Palmaz stent. A case report.
Pseudoaneurysm formation and vessel rupture are considered rare complications of percutaneous transluminal angioplasty (PTA), and few reported cases exist in the literature. The true incidence of pseudoaneurysm formation is unknown, for follow-up angiography is not routinely performed unless symptoms recur or persist. Currently, the only intervention widely accepted for angioplasty-induced pseudoaneurysm involves surgical excision or repair. The authors describe a case of successfully treated pseudoaneurysm with a noncovered stent.
Factors that interact with treatment to predict outcomes in substance abuse programs for the homeless.
This paper reviews the main treatment effects observed in the New Orleans Homeless Substance Abusers Project and then analyzes and discusses factors that appear to interact with treatment to produce successful treatment outcomes. Outcomes are assessed for alcohol and drug use, housing stability, and employment. Results show marginally significant positive effects for long-term treatment, but only for clients retained in treatment for more than about three months. Holding treatment variables constant, client characteristics that predict successful treatment outcomes include gender, education, age, psychiatric morbidity, drug of choice, attendance at AA/NA meetings, and prior treatment histories. Some of these same factors also predict success among controls. The significance, sign, and magnitude of these effects, however, varies depending on which specific outcome one analyzes. Thus, variation in treatment effectiveness is associated with entering conditions, as the literature suggests, but which entering conditions matter most depends on which specific outcome one examines.
Electrode potentials for bioreductive agents from neural networks.
The one-electron electrode potentials at pH 7 have been predicted to an average accuracy of about 70 mV for a number of nitrobenzenes, nitrofurans and nitroimidazoles using a neural network. The inputs were the heat of formation and the free energy of hydration of both the nitroarene and its radical anion. The heats of formation were calculated using semiempirical molecular orbital methods; the free energies of hydration were calculated using a modified Born equation with additional semiempirical terms. Since these inputs can be calculated quickly, the neural network promises to be very useful in the design of molecules such as bioreductive agents where the electrode potential is of crucial importance. The success of the neural network in this problem implies that the errors, primarily in the semiempirical heat of formation, are systematic, and offers the hope that these may be corrected in future generations of the semiempirical methods.
Controlling costs through "managed competition".
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Human IgG in immune complexes bound to human erythrocyte CR1 is recognized differently than human IgG bound to an erythrocyte surface antigen.
We have developed several methods, including a new use of magnetic cell separation techniques, to examine how human IgG bound to human erythrocytes can be recognized. We find that human IgG in complement-opsonized immune complexes bound to erythrocyte CR1 is less accessible to several probes than human IgG bound to the rhesus antigen on erythrocytes. These findings suggest that the mechanism by which immune complexes are removed and cleared from erythrocyte CR1 in the circulation is different from the mechanisms which lead to splenic clearance of IgG sensitized erythrocytes.
Health and social conditions of street children in Honduras.
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Homeless children. Two years later.
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Gun-related violence in and around inner-city schools.
OBJECTIVE: To assess the degree to which inner-city high school students are victimized by threat of or actual firearm attack. DESIGN: Cross-sectional survey. SETTING: Ten inner-city high schools in five cities in four states. PARTICIPANTS: A total of 1653 male and female inner-city high school students responding anonymously. SELECTION PROCEDURES: Volunteer, convenience sample. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Twenty-three percent of respondents were classified as victims. Major variables predicting victimization levels were gender, number of siblings, exposure to violence outside of school, and personal violence-related attributes. Only one in 10 victimizations appeared to be random (ie, not predicted by these variables). CONCLUSIONS: Violence in school is brought into, rather than generated by, the school. Victimized students have characteristics that put them at higher risk of victimization than other students. Given the large number of victimizations and the large number of respondents with risk characteristics, intervention at the individual level seems ineffective. Instead, alteration of community social structure and culture appears to be the appropriate, although difficult, avenue of change for gun-related victimization levels.
Children in and of the streets. Health, social policy, and the homeless young.
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Equine neural angiostrongylosis.
Verminous encephalomyelitis due to Angiostrongylus cantonensis larvae was diagnosed in 2 foals at necropsy. The principal clinical feature was tetraparesis, although history and neurological examination revealed progressive and multifocal neurological disease. At presentation, a tentative diagnosis of parasitic larval migration involving the central nervous system (CNS), presumably due to Strongylus vulgaris, was proposed. Dissection of the spinal cord in one case resulted in recovery of intact larvae of both sexes of A. cantonensis. In both foals, histopathology of the brain and spinal cord revealed nematode sections which were consistent with A. cantonensis larvae.