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Biomedical subjects

R E Johnson

Publications and source records attributed to R E Johnson.

At least 19 recordsLinked to original sources
PubMed1992

A controlled trial of buprenorphine treatment for opioid dependence.

OBJECTIVE: To assess the efficacy of buprenorphine for short-term maintenance/detoxification. DESIGN: A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase. SETTING: Outpatient facilities at the Addiction Research Center, Baltimore, Md. PATIENTS: One hundred sixty-two volunteers seeking treatment for opioid dependence. INTERVENTION: In addition to the medication, counseling using a relapse prevention model was offered but not required. PRIMARY OUTCOME MEASURES: Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence. RESULTS: Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups. CONCLUSIONS: Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.

Adult↗
PubMed1992

Weighing up the pros and cons: help-seeking by drug misusers in Baltimore, USA.

Forty drug misusers receiving treatment in Baltimore completed questionnaires, originally administered to drug misusers in London, about their reasons for seeking help and their worries about the treatment. Seeking help was related to the experiences of addiction, loss of control over life and financial and family difficulties. The main fears were of failing treatment. These responses are similar to those obtained in the London group. There was little correlation between objective assessment and subjects' views of their problems. This study illustrates the complexities of coming for treatment and it emphasises the need for social and medical help.

Adult↗
PubMed1992

Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome.

rad5 (rev2) mutants of Saccharomyces cerevisiae are sensitive to UV light and other DNA-damaging agents, and RAD5 is in the RAD6 epistasis group of DNA repair genes. To unambiguously define the function of RAD5, we have cloned the RAD5 gene, determined the effects of the rad5 deletion mutation on DNA repair, DNA damage-induced mutagenesis, and other cellular processes, and analyzed the sequence of RAD5-encoded protein. Our genetic studies indicate that RAD5 functions primarily with RAD18 in error-free postreplication repair. We also show that RAD5 affects the rate of instability of poly(GT) repeat sequences. Genomic poly(GT) sequences normally change length at a rate of about 10(-4); this rate is approximately 10-fold lower in the rad5 deletion mutant than in the corresponding isogenic wild-type strain. RAD5 encodes a protein of 1,169 amino acids of M(r) 134,000, and it contains several interesting sequence motifs. All seven conserved domains found associated with DNA helicases are present in RAD5. RAD5 also contains a cysteine-rich sequence motif that resembles the corresponding sequences found in 11 other proteins, including those encoded by the DNA repair gene RAD18 and the RAG1 gene required for immunoglobin gene arrangement. A leucine zipper motif preceded by a basic region is also present in RAD5. The cysteine-rich region may coordinate the binding of zinc; this region and the basic segment might constitute distinct DNA-binding domains in RAD5. Possible roles of RAD5 putative ATPase/DNA helicase activity in DNA repair and in the maintenance of wild-type rates of instability of simple repetitive sequences are discussed.

Adenosine Triphosphatases↗
PubMed1992

Evaluation of the reliability and validity of a measure of anxiolytic drug-use intensity for pharmacoepidemiologic studies.

OBJECTIVE: To assess the reliability and validity of a proposed new standard of drug-use intensity, the minimum marketed dose (MMD), using anxiolytic drugs as models. DESIGN: Retrospective, cohort design. SETTING: Staff model, nonprofit health maintenance organization. PATIENTS/PARTICIPANTS: Eighty-five patients who obtained one or more prescriptions for an anxiolytic, antidepressant, or sedative-hypnotic drug during three consecutive one-year time periods. Fifty-nine patients had a prescription filled during the year before the study. RESULTS: For anxiolytic drugs, the magnitude of the average correlation for the MMD measure of drug-use intensity was greater than the total number of prescriptions and the total number of dosage units. Discriminant validity was demonstrated because the MMD was not correlated with measures in unrelated therapeutic categories. Summed MMD units were shown to significantly predict physical impairment (criterion validity). CONCLUSIONS: The MMD measure of drug-use intensity was reliable and valid for anxiolytic drugs. These findings suggest that information gathered from automated prescription records may be a useful indicator of drug-use intensity in pharmacoepidemiologic studies.

Anti-Anxiety Agents↗
PubMed1992

Mycobacterium avium complex pulmonary disease presenting as an isolated lingular or middle lobe pattern. The Lady Windermere syndrome.

BACKGROUND: Pulmonary disease due to Mycobacterium avium complex (MAC-PD) radiographically resembles that due to tuberculosis; it preferentially affects elderly white men with predisposing pulmonary disorders (PDPD). METHODS: Twenty-nine patients with MAC-PD were identified from a community-based population, and the medical records and chest roentgenograms (CRs) of six with a previously undescribed pattern of MAC-PD were reviewed. The distinctive clinical and demographic features of these six patients were identified and summarized. RESULTS: All were women who tended to be elderly. None had clinically evident PDPD. The dependent portion of the lingula or its counterpart, the middle lobe, was initially affected. Hilar adenopathy, volume loss, and cavitary disease were uniformly absent. CONCLUSIONS: To account for the distinctive features of this syndrome, we offer the hypothesis that habitual voluntary suppression of cough may have led to the development of nonspecific inflammatory processes in these poorly draining lung regions, upon which MAC-PD engrafted. We offer the term, Lady Windermere's syndrome, to describe this pattern among elderly women and to suggest that their fastidiousness may be its root cause.

Aged↗
PubMed1992

Development of buprenorphine for the treatment of opioid dependence.

Data from these studies indicate that buprenorphine is efficacious in treating opioid dependence. It was possible to induct heroin addicts rapidly onto buprenorphine without precipitating an opioid withdrawal syndrome. A daily 8-mg SL dosage was sufficient to maintain individuals without producing reports of withdrawal symptoms. When buprenorphine was administered at the above dose every other day, however, mild withdrawal symptoms were reported, and responses to challenges with intravenously given hydromorphone appeared greater than when the challenges were given intramuscularly. From these results, the authors conclude that buprenorphine at this dose should be administered on a daily basis. These results are now being applied to a phase II outpatient clinical trial comparing buprenorphine with methadone.

Adult↗
PubMed1992

Background and design of a controlled clinical trial (ARC 090) for the treatment of opioid dependence.

This study represents the largest clinical trial reported to date that demonstrated the efficacy of buprenorphine for opioid dependence treatment (Johnson et al. 1992). Although the study design was adequate to demonstrate differences between treatment groups, there has not been a consensus regarding the most appropriate method for analyzing various outcome measures of this and similar studies. To present a comprehensive review of these methods, other chapters in this monograph focus on various analytical techniques for assessing one of these measures--urine toxicology screens--for illicit opioids.

Adult↗
PubMed1992

Nicotine chewing gum use in the outpatient care setting.

BACKGROUND: The purpose of this study was to assess nicotine gum use when prescribed in a nonresearch, routine outpatient setting. Special attention was given to comparing actual use patterns with established guidelines for use based on clinical research. METHODS: A randomly selected group of 612 patients who had received a prescription for nicotine gum during an 18-month period were surveyed regarding their smoking history and use of the gum. RESULTS: Most of the gum prescriptions (75%) were requested by patients rather than recommended by medical care providers. Less than one half of the users were heavy smokers. The reported amount of gum used was small, with more than one half reporting consumption of one box or less, and about one third reporting use of the gum for only 1 week or less. Larger amounts of gum use, however, were associated with abstinence from tobacco. Only one in 20 users attended a structured behavioral treatment program while using the gum. Over one half of the patients reported using nicotine gum to help them cut down on, rather than quit, smoking. CONCLUSIONS: Only a small percentage of the patients used the nicotine gum according to the established guidelines, and most of the patients used the gum in ways that have been shown to be ineffective for smoking cessation. Providers should educate their patients in the techniques that maximize the use and effectiveness of nicotine gum in smoking cessation.

Adolescent↗
PubMed1991

Use of naloxone in the assessment of opiate dependence.

All subjects participating in an outpatient study comparing treatments for opiate dependence were given a naloxone challenge to document their level of dependence. Subjects were assessed at 0, 10, 20, and 30 minutes following the administration of intramuscular naloxone (0.4 mg) using an opiate withdrawal assessment scale and measurements of pupillary diameter. Subjects' self reports of daily dollar amounts of opiate use and time since last use were also examined for possible correlation with withdrawal scale scores and pupillary measurements. A significant negative correlation was obtained between pupil diameter and time since last reported use of an opiate. Results indicated that the scale was a reliable indicator of opiate dependence. Ways in which it might be improved are discussed.

Adult↗
PubMed1991

The partial opioid agonist, buprenorphine, protects against lethal effects of cocaine.

Buprenorphine (0.3-3.0 mg/kg) produced dose-dependent protection against the lethal effects of cocaine in mice. The (+)-enantiomer of buprenorphine did not protect up to doses over 100 times greater than the lowest effective dose of its (-)-enantiomer. The protective effects were also produced by the opioid agonists morphine and methadone, but not by the opioid antagonist, naltrexone. Low doses of naltrexone (0.3-1.0 mg/kg) blocked the protective effects of buprenorphine. Protection conferred by buprenorphine was not observed in CXBK mice, a recombinant inbred strain relatively devoid of mu-opioid receptors. Thus, buprenorphine appears to protect against the lethal effects of cocaine by a process mediated by mu-opioid receptors. The present results should provide some additional safety assurance in future clinical trials with buprenorphine, especially in outpatient trials where cocaine abuse may continue along with treatment.

Animals↗
PubMed1991

Human pharmacology and abuse potential of nalmefene.

Nalmefene hydrochloride was administered to six male volunteers with histories of opiate abuse using a double-blind, randomized, Latin square design to determine if it produced typical morphine-like effects. A comparison of physiologic and subject- and observer-reported effects was made between morphine, 15 and 30 mg given intramuscularly; nalmefene, 25, 50, and 100 mg given orally; and placebo. Drowsiness or sleepiness was the most common drug effect reported after the administration of each treatment. Only morphine produced miosis and increased subject-reported euphoria and "drug liking." Neither drug increased Addiction Research Inventory subscale scores measuring dysphoria or sedation or produced changes on the Profile of Mood States questionnaire. Adverse effects reported only after the administration of nalmefene included agitation/irritability and muscle tension; these did not appear to be dose related. The data indicated that nalmefene did not produce typical morphine-like effects and has no apparent abuse potential.

Adult↗
PubMed1991

Comparing sources of drug data about the elderly.

OBJECTIVE: This project assessed the extent of agreement between drug-taking data obtained from an in-home assessment and that obtained from an automated outpatient pharmacy system and from a mail questionnaire. DESIGN: The underlying assumption is that an in-home assessment provides the most complete information (criterion standard) about the prescription medications being taken. The drug data from the mail questionnaire and automated outpatient pharmacies were compared with that from the in-home assessment by use of t tests and measures of sensitivity, specificity, and positive predictive value. SETTING: Kaiser Permanente, Northwest Region, a prepaid group practice HMO. PARTICIPANTS: All elderly HMO members enrolled in the Social HMO demonstration project who had a comprehensive assessment within 30 days of returning a mail questionnaire between March 1986 and March 1988 (n = 83 frail elderly). MAIN OUTCOME MEASURES: The number of medications currently being taken and the number of different therapeutic classes of drugs being taken per elderly HMO member. MAIN RESULTS: The in-home assessment and the automated prescription system closely agreed on the number of different medications and the different therapeutic classes of prescription drugs being taken. The in-home assessment and mail questionnaire were in less agreement. Agreement was less for non-prescription drugs. CONCLUSIONS: An automated prescription system is an adequate source of information about the prescription drugs currently being taken by frail elderly HMO enrollees with a prepaid prescription drug benefit.

Aged↗
PubMed1991

Mycobacterium avium complex pulmonary disease. Incidence, presentation, and response to therapy in a community setting.

The experience with pulmonary disease caused by Mycobacterium avium complex (MAC-PD) was examined over a 12-yr period in a nonreferral setting. The 29 patients with the disease constituted 30% of all pleuropulmonary mycobacterioses. The mean annual incidence rate was 1/100,000. Sixty-two percent of patients were female, the majority of whom had no discernible preexisting pulmonary disorder to account for their susceptibility. A short- and long-term favorable response to therapy was observed in more than 90% of the 16 patients treated with intent to cure. Suggested as plausible explanations for the favorable response rate compared with previous studies originating in referral settings were: absence of adverse selection as shown by a smaller proportion of patients with far-advanced cavitary disease or with previous treatment failure, and a larger proportion of female patients. A previously unreported pattern of MAC-PD was observed: disease limited to the lingula or middle lobe occurred in 21% of the patients, all female. A rarely identified pattern, primary disease in a 3-yr-old exposed to pet birds, is reported.

Adult↗
PubMed1991

Recombinant alpha-interferon and verruca plantaris. A review of the literature.

The authors review the literature and report the mechanisms of action, chemical properties, pharmacokinetics, adverse effects, and clinical studies of recombinant alpha-interferon. The authors believe that clinical trials should be performed with recombinant alpha-interferon therapy on verruca plantaris to prove or disprove the effectiveness of interferon as a potential treatment modality for these commonly encountered lesions.

Clinical Trials as Topic↗
PubMed1990

Safety and side-effects of buprenorphine in the clinical management of heroin addiction.

Sublingual buprenorphine (8 mg) was administered to heroin-dependent addicts daily for 18 days and continued from day 19-day 36 either daily or on alternate days. Final data are reported on 18 subjects. The number of self-reported symptoms reviewed as potential adverse drug reactions ranged from 1 to 88 per participant. None was considered to be related definitely to the study medication, and there were no reporting differences between the two dosing regimens. Forty-five reactions were considered probably related to buprenorphine: sedation/drowsiness (three reports) and constipation (42 reports). It was concluded that these were anticipated drug effects rather than adverse reactions. Although some participants showed increases in serum aminotransferase levels, those increases could not be directly attributed to buprenorphine. We conclude that buprenorphine was well tolerated, but further study is needed in this population to delineate the possible attributable risk of the drug to hepatic dysfunction in this population.

Administration, Sublingual↗
PubMed1990

Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal.

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours.

Adult↗
PubMed1990

Acyclovir use and its surveillance in a general population.

This study examined the extent and patterns of use of acyclovir in a health maintenance organization (HMO) population. The development and implementation of a system to survey acyclovir users for possible acute adverse effects is also described. Acyclovir users were members of Kaiser Permanente (KP), Northwest Region, who received one or more prescriptions for acyclovir from an automated outpatient prescription system over a two-year period (1986 and 1987). KP members with genital herpes were identified from the automated Outpatient Utilization System, which abstracts medical record data from a random sample of about two percent of KP members. Acyclovir users with hospital admissions were identified from the automated KP hospital discharge abstract system. During the two years, there were 2940 users who received a total of 6182 prescriptions for acyclovir; 47 percent used oral acyclovir and 56 percent of prescriptions were for the oral dosage form. Females received two-thirds of the prescriptions, and people 15 through 45 years of age received 80 percent of the prescriptions. The estimated incidence density of oral acyclovir usage was 2.3/1000 KP members. Most oral acyclovir prescriptions were for the treatment of genital herpes. More than 60 percent of the prescriptions appeared to be for first treatment, more than 30 percent for repeat treatment, and about 6 percent for continuing treatment. Hospitalizations of oral acyclovir users appeared to be unrelated to the use of the drug.

Acyclovir↗