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R Malcolm

Publications and source records attributed to R Malcolm.

At least 19 recordsLinked to original sources
PubMed2003

A protein interaction map of Drosophila melanogaster.

Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid-based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

Animals↗
PubMed2002

The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.

OBJECTIVE: Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. DESIGN: This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). SETTING: A university medical center substance abuse clinic in Charleston, SC. PATIENTS: One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. INTERVENTIONS: Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. MAIN OUTCOME MEASURES: The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. RESULTS: Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. CONCLUSIONS: Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Adult↗
PubMed2001

Hydrogeochemistry of groundwater in coastal wetlands: implications for coastal conservation in Scotland.

Groundwater in a shallow coastal aquifer in north east Scotland was monitored over the hydrological year October 1996-September 1997. Groundwater flow from inland areas sustained freshwater conditions in a dune-wetland complex of conservation importance. In particular, seasonal flooding of the coastal wetlands due to water table rise provided important roosting and breeding habitats for waterfowl. Hydrogeochemical analysis revealed that groundwater in the shallow sand aquifer was circum-neutral, and non-saline, despite being within 50 m of the sea and only 1 m above the mean high water mark. Calcium and HCO3 were the dominant cation and anion respectively, reflecting weathering processes in the aquifer. Use of the geochemical code NETPATH indicated that calcite weathering in shell fragments within the sand was the primary source of Ca and alkalinity generation. The concentrations of Na and Cl were also important, though these can be explained primarily by atmospheric inputs from precipitation. In detail, the spatial and temporal variation in groundwater chemistry was remarkably complex for what intuitively appeared a simple aquifer system. Temporal variations in groundwater chemistry mainly related to the seasonal event of groundwater recharge. Thus, the main period of rising groundwater levels resulted in a marked dilution of solutes in the aquifer, implying that water storage greatly increased in a relatively short period. A period of several weeks appeared to be required for dissolution processes to proceed to equilibrium. Spatial variation in groundwater chemistry appears to relate to the spatial distribution of geochemical processes in different hydrogeological units. Sulphate reduction, alkalinity generation and Fe precipitation appear to be locally important processes. The chemistry of groundwater maintains the wetland habitat by providing freshwater conditions that allow populations of various plant species to flourish. The potentially large recharge catchments of coastal wetlands, together with increasing pressures in the coastal zone, dictate that pollution can threaten the integrity of hydrochemical processes and requires careful monitoring if freshwater wetlands are to maintain their conservation importance.

Calcium↗
PubMed2001

New developments in the pharmacotherapy of alcohol dependence.

Neuroscientific underpinnings and pharmacotherapeutic treatments of substance use disorders are rapidly developing areas of study. In particular, there have been exciting new developments in our understanding of the involvement of excitatory amino acid neurotransmitter systems and the opiate and serotonin systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in subtypes of individuals with alcoholism. In this article, new developments in the pharmacotherapy of alcohol dependence will be reviewed. In particular, the use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes will be discussed. New data on opiate antagonists and acamprosate, an agent that exerts actions through excitatory amino acid systems in relapse prevention, will be reviewed. Finally, there will be a review of new data concerning the use of serotonin reuptake inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy.

Acamprosate↗
PubMed2001

Update on anticonvulsants for the treatment of alcohol withdrawal.

Some anticonvulsants have been shown to be as effective as some benzodiazepines for the treatment of alcohol withdrawal. Anticonvulsants may offer advantages over benzodiazepines in the outpatient treatment of alcohol withdrawal: they lack abuse potential, have minimal interactions with alcohol, and may be more effective in ameliorating psychiatric symptoms of alcohol withdrawal. Carbamazepine appears to be as effective as lorazepam and oxazepam in ameliorating the symptoms of alcohol withdrawal. In addition, a recent study indicates that carbamazepine may suppress post-withdrawal alcohol use. Divalproex may also reduce symptoms of alcohol withdrawal, based on several open-label studies. However, both carbamazepine and divalproex have limited usefulness in alcoholics with severe hepatic or hematologic complications. Newer anticonvulsants, such as gabapentin and vigabatrin, also appear to reduce alcohol withdrawal symptoms in preclinical and open-label clinical trials while lacking the toxicities of carbamazepine and divalproex. Controlled trials are underway exploring the efficacy and safety of newer anticonvulsants for the treatment of alcohol withdrawal.

Anticonvulsants↗
PubMed2001

Adverse outcomes in a controlled trial of pergolide for cocaine dependence.

We conducted a double-blind, multiple dose comparison study of pergolide versus placebo for the treatment of cocaine dependence. In the present study, we examined patients who met criteria for cocaine dependence without comorbid alcohol dependence (N = 255). Study completion rates favored placebo (48.9%) over the low dose (33.3%) and high dose (21.5%) pergolide subjects (chi2(2) = 14.17, p < or = 0.001). Treatment effectiveness scores (TES) were significantly higher for the placebo group (31.7) than the low dose (25.2) and high dose (14.2) pergolide groups (F2,252 = 6.21, p = 0.002). There were no significant differences in side effect profiles after first dose of pergolide or placebo, or at study termination. Results of this study suggest that pergolide was not efficacious in the treatment of cocaine dependence due to reduced study participation. Caution regarding the outpatient use of pergolide in similar populations is warranted.

Adolescent↗
PubMed2001

Gabapentin in the treatment of cocaine dependence: a case series.

BACKGROUND: Although multiple medications have been studied for the treatment of cocaine dependence, no medication has been shown to have a robust effect on craving and use. This pilot project was designed to evaluate the safety and tolerability of gabapentin in subjects with cocaine dependence. METHOD: Thirty cocaine-dependent subjects (DSM-IV criteria) were enrolled in an 8-week, open-label trial of 1,200 mg/day of gabapentin in divided doses. Urine drug screens, subjective measures of craving, and cocaine use interviews were conducted at each weekly visit. RESULTS: Baseline rating of amount and frequency of craving decreased significantly by week 8 (78% vs. 25% for amount, p = .000; 74% vs. 23% for frequency, p = .004). Positive urine drug screens for cocaine decreased from 86% at baseline to 29% at weeks 4 and 8. There were no reports of significant side effects or adverse events. CONCLUSION: This pilot study indicates that gabapentin is safe and well tolerated and may be beneficial in the treatment of cocaine dependence. A placebo-controlled trial would be of interest.

Acetates↗
PubMed2000

A double-blind, placebo-controlled outpatient trial of pergolide for cocaine dependence.

Results of preclinical studies suggest that pergolide, a mixed D(1)/D(2) dopamine receptor agonist, may be useful in treating cocaine dependence. To empirically investigate this possibility, we conducted a 5-year, double-blind, placebo-controlled clinical trial of two doses of pergolide (0.05 and 0.25 mg bid) in subjects with cocaine dependence and combined cocaine/alcohol dependence. Data analysis was performed on an intent to treat population (N=358) and a per protocol population (N=108) with urine drug screens (UDS) used as the main outcome measure. There were no significant effects on UDS at either pergolide dose. Pergolide had no significant effect on alcohol use in the comorbid alcohol/cocaine dependence group. Pergolide does not appear to have clinical value in the treatment of cocaine dependence or in decreasing alcohol use in cocaine-dependent individuals at the presently studied doses.

Adolescent↗
PubMed2000

Multiple previous detoxifications are associated with less responsive treatment and heavier drinking during an index outpatient detoxification.

Investigators have found a relationship between the number of previous alcohol withdrawals (AWs) and severity of withdrawal. We evaluated patients with multiple previous AWs, as compared to those with 0-1 previous withdrawals, in an outpatient detoxification trial comparing lorazepam (LZ) to carbamazepine (CBZ). A mixed model analysis of covariance was used to analyze Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores as a function of detoxification history (0-1 vs. 2 or more), drug group (CBZ vs. LZ), assessment day, and hours since last drink. The mixed model analysis of covariance (ANCOVA) indicated a significant detoxification history by assessment day interaction (P< or =.03). Least square means associated with this interaction suggested that the CIWA-Ar scores for the multiple detox patients declined more slowly than those with 0-1 previous detoxifications. Patients with multiple detoxes were 150% more likely to experience a heavy drinking day during treatment (P< or =.03). The multiple detox group drank more each drinking day (P=.001) and a greater proportion of this group had early heavy drinking (P=.0002). In the present study, intensity of AW symptoms and early heavy drinking were independent of treatment medications and were more common in patients who had previously undergone multiple treatments for AW.

Adult↗
PubMed2000

Recurrent detoxification may elevate alcohol craving as measured by the Obsessive Compulsive Drinking scale.

Research has demonstrated a relationship between the number of previous alcohol detoxifications and increased severity of the alcohol withdrawal syndrome (AWS) that is hypothesized to be similar to an electrophysiologic "kindling process." Application of a "kindling" model to AWS suggests that neuroadaptation of the central nervous system to repeated detoxifications may also cause neurobehavioral alterations that may affect "craving." This study examined craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS) in 67 adult outpatients meeting DSM-IV criteria (American Psychiatric Association, 1994) for alcohol dependence and AWS having either < 2 and > or = 2 previous detoxifications. Results of ANCOVA revealed that patients with > or = 2 previous detoxifications had higher scores on a scale that measures obsessive thoughts about alcohol, drinking urges and behaviors, and a composite of these scores after controlling for alcohol dependence severity, depressive symptoms and number of drinks 2 weeks prior to the study. Findings emphasize the need to address craving and other psychological variables with respect to treatment of AWS.

Adult↗
PubMed2000

Divalproex in the treatment of alcohol withdrawal.

The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group x CIWA-Ar score interaction [F(8,72) = 2.57, p < or = .01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p < or = .001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal.

Adult↗
PubMed1999

Carbohydrate-deficient transferrin and alcohol use in medical examiner cases.

Carbohydrate-deficient transferrin (CDT) has been studied as an index of heavy alcohol use. The present study evaluates the utility of CDT as a marker for chronic alcohol use in medical examiner cases. Over a 5-month period, serum specimens were collected in consecutive deaths that were referred to the medical examiner's office (N = 25). Manner of death was accidental in nine cases, homicide/suicide for eight cases, and natural causes for seven cases. Fifteen of the 17 cases having alcohol abuse had positive CDT levels above threshold, indicating chronic use (sensitivity 88%). Eight cases had no evidence of alcohol abuse but three of these cases had CDT levels also above threshold (specificity 63%). There was no correlation between serum CDT levels and the time of death to blood collection for the total sample, indicating that CDT is stable postmortem for at least 36 h. CDT appears to have value as a marker of ante-mortem alcohol use prior to time of death in medical examiner cases.

Adolescent↗
PubMed1997

Pergolide mesylate. Adverse events occurring in the treatment of cocaine dependence.

In this preliminary report from a placebo-controlled, double-blind, dose-response study on the use of pergolide mesylate for cocaine dependence in outpatients 8 out of 235 subjects noted adverse events requiring breaking of the blind. Events occurred at or within 7 days of receiving the first dose of medication and included side effects (four cardiovascular, one psychiatric); drug-drug interactions (one): and clinical exclusions (two pregnancies). Two anecdotes of illicit abuse are reported. Although efficacy is unestablished, pergolide appears to be safe in the early treatment of cocaine dependence except where there are relative contraindications.

Adult↗
PubMed1996

Alcohol treatment: measurement of effectiveness by global outcome.

Traditional methods of data analysis in alcohol studies focus only on alcohol consumption as dependent variables rather than considering a global, person-in-environment perspective. The purpose of this study was to evaluate treatment outcome in a clinical trial using dimensions of life functioning in addition to quantity-frequency measures of alcohol use. Subjects were male veterans suffering from high levels of anxiety in addition to alcohol dependence who were randomly assigned to treatment with a placebo or buspirone. Results show that global outcome measures did not reveal differences from standard treatment outcome measures in this study. All of those subjects who were drinking heavily, and most of those drinking moderately, were experiencing life problems. However, studies with other designs and with larger sample sizes are needed.

Adult↗