Intravenous drug use and HIV.
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Biomedical subjects
Publications and source records attributed to Robert G Newman.
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Untreated opiate addiction remains a major health care crisis in New York and in most other urban centers in America. Optimism for closing the gap between need and demand for treatment and its availability has greeted the recent approval of a new opiate medication for addiction, buprenorphine--which unlike methadone may be prescribed by independent, office-based practitioners. The likelihood of buprenorphine fulfilling its potential is assessed in the light of the massive expansion of methadone treatment more than 30 years earlier. It is concluded that the key, indispensable ingredient of success will be true commitment on the part of Government to provide care to all those who need it.
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OBJECTIVES: To describe and evaluate a pilot methadone maintenance program for heroin-dependent inmates of Las Malvinas men's prison in San Juan, Puerto Rico. METHODS: Data from self-report of inmates' drug use before and during incarceration, attitudes about drug treatment in general and methadone maintenance in particular, and expectations about behaviors upon release from prison and from testing inmates' urine were analyzed comparing program patients (n=20) and inmates selected at random from the prison population (n=40). Qualitative data obtained by interviewing program staff, the correctional officers and superintendent, and commonwealth officials responsible for establishing and operating the program were analyzed to identify attitudes about methadone and program effectiveness. RESULTS: Heroin use among prisoners not in treatment was common; 58% reported any use while incarcerated and 38% reported use in past 30 days. All patients in the treatment program had used heroin in prison in the 30 days prior to enrolling in treatment. While in treatment, the percentage of patients not using heroin was reduced, according to both self-report and urine testing, to one in 18 (94% reduction) and one in 20 (95% reduction), respectively. Participation in treatment was associated with an increased acceptance of methadone maintenance. Prison personnel and commonwealth officials were supportive of the program. CONCLUSIONS: The program appears to be a success, and prison officials have begun an expansion from the current ceiling of 24 inmates to treat 300 or more inmates.
This case report provides no basis for drawing any conclusions regarding possible adverse effects of use of Ecstasy.
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3-(4-Methylcoumarin-7-yloxy)methylindole-4,7-diones were synthesised as model prodrugs in order to investigate the correlation between rates of reductive elimination from the (indolyl-3-yl)methyl position with reductive metabolism by hypoxic tumor cells and NADPH: cytochrome P450. Rates of elimination of the chromophore/fluorophore (7-hydroxy-4-methylcoumarin) following one-electron reduction of indolequinones to their semiquinone radicals (Q*-) was measured by pulse radiolysis utilising spectrophotometric and fluorometric detection. Incorporation of a thienyl or methyl substituent at the (indol-3-yl)CHR-position (where R=thienyl or methyl adjacent to the phenolic ether linking bond) significantly shortened the half-life of reductive elimination from 87 to 6 and 2 ms, respectively. Elimination from the methyl substituted analogue can thus compete effectively with the reaction of the semiquinone radical with oxygen at levels typically present in tumours (half-life approximately 1.8 ms at 0.5% O2). Chemical kinetic predictions were confirmed by metabolism in breast tumour MCF-7 cells between 0-2.1% O2. Rates of reductive release of the fluorophore from the non-fluorescent parent indolequinones (R=H, Me, thienyl) were similar under anoxia ( approximately 1.7 nmol coumarinmin(-1)mg protein(-1)) reflecting the similarity in one-electron reduction potential. Whereas coumarin release from the indolequinone (R=H) was completely inhibited above 0.5% O2, the enhanced rate of reductive elimination when R=thienyl or Me increased the metabolic rate of release to approximately 0.35 and 0.7 nmol coumarinmin(-1)mg protein(-1), respectively at 0.5% O2; complete inhibition occurring by 2.1% O2. Similar 'oxygen profiles' of release were observed with NADPH: cytochrome P450 reductase. In conclusion, it is possible to modify rates of reductive elimination from indolequinones to control the release of drugs over a range of tumour hypoxia.
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