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Biomedical subjects

M E McCaul

Publications and source records attributed to M E McCaul.

At least 19 recordsLinked to original sources
PubMed2006

Alcohol and drug use disorders, HIV status and drug resistance in a sample of Russian TB patients.

SETTING: Alcohol use, tuberculosis (TB) drug resistance and human immunodeficiency virus (HIV) risk behavior are of increasing concern in Russian TB patients. DESIGN: A prevalence study of alcohol use and HIV risk behavior was conducted in a sample of 200 adult men and women admitted to TB hospitals in St Petersburg and Ivanovo, Russia. RESULTS: Of the subjects, 72% were men. The mean age was 41. Active TB was diagnosed using a combination of chest X-ray, sputum smears and sputum cultures. Sixty-two per cent met DSM-IV criteria for current alcohol abuse or dependence. Drug use was uncommon, with only two patients reporting recent intravenous heroin use. There was one case of HIV infection. The mean total risk assessment battery score was 3.4. Depression was present in 60% of the sample, with 17% severely depressed. Alcohol abuse/dependence was associated with an eight-fold increase in drug resistance (OR 8.58; 95% CI 2.09-35.32). Patients with relapsing or chronic TB were more likely to meet the criteria for alcohol abuse/dependence (OR 2.56; 95% CI 1.0-6.54). CONCLUSION: Alcohol use disorders are common in patients being treated for active TB, and are associated with significant morbidity. Additional surveys are needed to examine the relationship between alcohol use disorders and anti-tuberculosis drug resistance.

Adult↗
PubMed2004

GABRA6 gene polymorphism and an attenuated stress response.

The glucocorticoid component of the stress response has been the subject of intense scientific scrutiny because of the wide ranging pathological consequences resulting from excess glucocorticoid exposure, including mood and anxiety disorders, and cognitive impairment. Exposure to stress activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic adrenomedullary system, which are regulated by neuronal pathways, including the inhibitory GABAergic (gamma-aminobutyric acid) system. Approximately 60% of the variance in glucocorticod levels may be attributable to genetic individual differences. In the present study, 56 healthy subjects underwent genotyping to determine the influence of the T1521C single nucleotide polymorphism (SNP) in the GABA(A)alpha6 receptor subunit gene (GABRA6) on the hormonal and autonomic responses to psychological stress induced by the Trier Social Stress Test (TSST). Adrenocorticotropin (ACTH), cortisol, diastolic blood pressure, and mean blood pressure responses to the TSST were significantly greater in subjects homozygous for the T allele or heterozygous compared to subjects homozygous for the C allele. Behavioral data was collected employing the Revised NEO Personality Inventory (NEO PI-R); subjects homozygous for the C allele scored significantly lower on the Extraversion factor compared to subjects homozygous for the T allele or heterozygous. These results suggest that the T1521C polymorphism in the GABRA6 gene is associated with specific personality characteristics as well as a marked attenuation in hormonal and blood pressure responses to psychological stress.

Adrenocorticotropic Hormone↗
PubMed2001

Predictors of outpatient treatment retention: patient versus substance use characteristics.

The present study examined predictors of participation and retention for patients treated at an urban, hospital-based outpatient substance abuse treatment clinic. All patients were interviewed using the Addiction Severity Index (ASI) at the time of admission. Based on lifetime diagnostic history of psychoactive substance abuse/dependence, patients (N=268) were classified as: alcohol-only, drug(s)-only, and alcohol+drug(s). Alcohol-only patients were significantly older, more likely to be Caucasian, married, have less than a high school education, and be employed than drug-only or alcohol/drug patients. Using multiple regression analysis, substance use status did not predict treatment participation and retention, whereas race, gender and employment composite score were significant predictors. Specifically, patients attended more sessions and remained in treatment longer if they were Caucasian, male and had a high employment composite score. These findings suggest that type of substance abuse may be overemphasized as a predictor of outpatient drug-free treatment retention, and that greater emphasis should be placed on tailoring treatment to patients' cultural, gender and vocational needs.

Adult↗
PubMed2001

Naltrexone dampens ethanol-induced cardiovascular and hypothalamic- pituitary-adrenal axis activation.

Alcohol ingestion activates the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. This study examined naltrexone effects on alcohol-induced increases in physiological responses and their association with alcohol liking. Using a within-subjects design, heavy drinking men (N = 19) were maintained on each of three naltrexone doses (0, 50, and 100 mg, p.o.) over an 8-day inpatient stay. Within each naltrexone dose, subjects had three alcohol challenge sessions (none, moderate, high) in random order. Autonomic, subjective and endocrine measurements were collected regularly prior to and following alcohol administration. High-dose alcohol ingestion increased heart rate, diastolic blood pressure, skin temperature, ACTH, cortisol and liking of drink effects; responses following the moderate alcohol dose were less consistent. Naltrexone significantly dampened alcohol-induced increases in heart rate, diastolic blood pressure, hormone levels and subjective liking of drink effects. This dampening of cardiovascular and hormonal responses may contribute to the therapeutic effectiveness of naltrexone for reducing alcohol liking and decreasing relapse in alcohol-dependent persons.

Adult↗
PubMed2001

Confirmation that offspring from families with alcohol-dependent individuals have greater hypothalamic-pituitary-adrenal axis activation induced by naloxone compared with offspring without a family history of alcohol dependence.

BACKGROUND: This study was designed to confirm our previous findings that nonalcoholic offspring from families with alcohol-dependent individuals have greater hypothalamic-pituitary-adrenal axis activation induced by opioid blockade compared with nonalcoholic subjects without a family history of alcohol dependence. METHODS: Sixty-four nonalcoholic subjects aged 18 to 25 years were enrolled in the protocol. Twenty-seven subjects were offspring from families with alcohol dependence and were designated as family history-positive subjects (FHP). Thirty-seven subjects were biological offspring of non-alcohol-dependent parents and were designated as family history-negative subjects (FHN). Subjects received naloxone hydrochloride (0, 50, 125, 375, and 500 microg/kg) in double-blind, randomized order; adrenocorticotropin (ACTH) and cortisol were monitored over 120 min. RESULTS: No hormone differences at baseline or during placebo administration were identified between FHP and FHN subjects. FHP subjects had greater ACTH and cortisol response to opioid receptor blockade induced by naloxone hydrochloride compared with FHN subjects. CONCLUSIONS: These observations confirm previous findings that differences in ACTH and cortisol dynamics between FHP and FHN subjects can be unmasked by opioid receptor blockade.

Adolescent↗
PubMed2000

Plasma adrenocorticotropin responses to opioid blockade with naloxone: generating a dose-response curve in a single session.

We examined two methods of generating a dose-response curve to the opioid receptor antagonist naloxone. In 15 healthy male subjects (18-25 years) plasma adrenocorticotropin (ACTH) responses to five doses of naloxone studied over 5 separate days were compared to plasma ACTH responses to five incremental doses of naloxone studied within a single session. There was a statistically significant positive correlation in ACTH responses (area under the curve and peak) between dosing methods. Furthermore, the doses of naloxone that produced half-maximal and maximal ACTH response were similar. The comparability of ACTH responses between the two naloxone dosing techniques, combined with the safety and ease associated with the single-session methodology, underscores the usefulness of the single-session technique for future investigations.

Adolescent↗
PubMed2000

Naltrexone alters subjective and psychomotor responses to alcohol in heavy drinking subjects.

Preclinical studies support endogenous opioid system involvement in alcohol reinforcement and consumption; however, recent clinical trials and human laboratory studies have provided mixed findings of the effects of naltrexone (a non-selective opioid antagonist) on alcohol responses. This study used a within-subject design (n = 23) to investigate naltrexone effects (0, 50 and 100 mg qd) on subjective and psychomotor responses to alcohol (none, moderate, high) in heavy drinkers. Before alcohol administration, subjects reported decreased desire to drink alcohol when maintained on 50 mg compared with placebo naltrexone. Following alcohol administration, active naltrexone significantly increased subjective ratings of sedative, and unpleasant/sick effects and decreased ratings of liking, best effects and desire to drink. Naltrexone generally did not alter subjective or objective indicators of drunkenness. Finally, high doses of naltrexone and alcohol interacted to produce the greatest decreases in liking and best effects. Findings support the role of endogenous opioids as determinants of alcohol's effects and suggest that naltrexone may be particularly clinically useful in those treatment patients who continue to drink heavily.

Adult↗
PubMed2000

Pregnant, alcohol-abusing women.

BACKGROUND: This paper reviews the literature on the identification and treatment of pregnant, alcohol-abusing women, with special emphasis on poor women who have access to treatment through Medicaid. METHODS: The paper discusses the gaps and controversies in the literature and suggests five priorities for future research. RESULTS: Studies that attempt to identify pregnant women who drink conclude that heavier drinkers enter prenatal care later than other women, that many health care providers fail to recognize alcohol abuse by pregnant women, and that research on screening techniques is still in the early stages. Treatment research suggests that comprehensive, holistic treatment approaches, as well as brief interventions and case management, have been successful in reducing prenatal alcohol use. Debate continues over whether treatment should be voluntary. CONCLUSIONS: The five areas identified as priorities for future research include (1) developing reliable and valid measures to identify alcohol abuse in pregnant women, (2) creating training programs for providers, (3) generating programs to reduce barriers to care, (4) determining which treatment programs are most successful, and (5) estimating the costs and benefits of various treatment approaches.

Alcoholism↗
PubMed2000

Serum 6-beta-naltrexol levels are related to alcohol responses in heavy drinkers.

BACKGROUND: There is strong evidence for the role of the endogenous opioid system in alcohol reinforcement and consumption; however, recent human laboratory studies and clinical trials have reported mixed effects of naltrexone (a nonselective opioid antagonist) on alcohol-related behaviors. This paper reports a secondary data analysis of a human laboratory study that examines the relationship between serum levels of 6-beta-naltrexol, the major, biologically active metabolite of naltrexone, and subjective effects of alcohol. METHODS: The study used a within-subjects design to examine the effects of naltrexone (0, 50, and 100 mg/day) on subjective responses to alcohol (none, moderate, and high dose) in heavy drinkers (n = 23). Each subject received three doses of naltrexone in random order; each naltrexone dose was administered over an 8 day period on an inpatient unit, with a 1 week outpatient washout between doses. After stabilization at each of the naltrexone doses, subjects participated in three alcohol challenge sessions (none, moderate, and high dose) in random order; thus, each subject participated in a total of nine alcohol administration sessions. RESULTS: Doubling the naltrexone dose (50 vs. 100 mg/day) doubled the mean serum 6-beta-naltrexol levels. At each naltrexone dose, there was a 4-fold range in 6-beta-naltrexol levels across subjects. Before alcohol administration, higher 6-beta-naltrexol levels were associated with higher ratings of sedation. After high-dose alcohol administration, higher 6-beta-naltrexol levels were associated with significantly lower ratings of liking and best effects. CONCLUSIONS: These findings provide further evidence of the involvement of the opioid system in the modulation of alcohol effects and suggest that serum 6-beta-naltrexol concentrations may be important in predicting therapeutic response to naltrexone.

Adult↗
PubMed1998

Family history of alcoholism and hypothalamic opioidergic activity.

BACKGROUND: This study was designed to assess whether nonalcoholic offspring from families with a high density of alcohol-dependent individuals have altered endogenous central nervous system opioid activity. Naloxone hydrochloride stimulates plasma cortisol by blocking opioidergic input on the corticotropin-releasing factor neuron, thereby providing a noninvasive method for measuring hypothalamic opioid tone. METHODS: Forty-eight nonalcoholic subjects aged 18 to 25 years were enrolled in a protocol to measure endogenous opioid activity by inducing opioid receptor blockade with the receptor antagonist, naloxone. Twenty-six subjects were offspring from families with a high density of alcohol dependence and were designated as family history-positive subjects. Twenty-two subjects were biological offspring of nonalcohol-dependent parents and designated as family history-negative subjects. Subjects received naloxone hydrochloride (0, 125, and 375 microg/kg) in double-blind, randomized order. Serum cortisol levels were monitored. RESULTS: Family history-negative subjects had a graded cortisol response to each dose of naloxone. In contrast, family history-positive subjects achieved a maximal cortisol response to the 125-microg/kg dose of naloxone hydrochloride with no further increase in cortisol levels observed following the 375-microg/kg dose. Family history-negative subjects had a diminished cortisol response to the 125-microg/kg dose compared with the family history-positive subjects. Plasma naloxone concentrations did not differ between family history groups. CONCLUSIONS: Individuals from families with a high density of alcohol dependence are more sensitive to naloxone compared with offspring of nonalcohol-dependent parents. This implies that individuals with a family history of alcohol dependence have diminished endogenous hypothalamic opioid activity.

Adolescent↗
PubMed1998

Substance abuse vulnerability in offspring of alcohol and drug abusers.

Epidemiological research has clearly demonstrated the importance of a family history as a determinant of future alcohol and, possibly, drug use in offspring of alcoholics. Laboratory studies have examined a wide range of potential markers both in the presence and absence of alcohol challenge, which may predict those subjects at high risk for the future development of alcoholism. While this body of research has yielded several replicable differences in FHP and FHN subjects, it also has been marked by many discrepancies in outcomes across studies. Future refinements in subject ascertainment and laboratory methodologies may help to bring greater procedural uniformity and consistency in study outcomes.

Alcoholism↗
PubMed1997

Cost-effectiveness of treatment for drug-abusing pregnant women.

Neonatal intensive care unit (NICU) and drug treatment costs were compared in two groups of pregnant drug abusing women: 100 admissions to a multidisciplinary treatment program and active in care at the time of delivery and 46 controls not entering drug treatment. Clinical measures included urine toxicology at delivery, infant birthweight. Apgar scores and need for and duration of NICU services. Cost measures included drug treatment and NICU costs. Treatment patients showed better clinical outcome at delivery, with less drug use and higher infant estimated gestational age, birthweight and Apgar scores. Infants of treatment patients were also less likely to require NICU services and, for those that did, had a shorter stay. When total cost was examined (including drug treatment), mean net savings for treatment subjects was $4644 per mother/infant pair. The study demonstrates the cost-effectiveness of treatment for pregnant drug abusing women, with savings in NICU costs exceeding costs of drug treatment.

Adult↗
PubMed1996

Detecting alcohol problems in drug-dependent women of childbearing age.

Alcohol problems frequently go undetected in drug-dependent individuals. In women of childbearing age, the consequences of unrecognized alcohol problems can be severe. Unfortunately, many drug treatment programs lack resources to conduct formal diagnostic interviews with all program admissions. Using the Structured Clinical Interview for DSM-III-R (SCID) as the "gold standard," the present study compared four clinical tools for assessing alcohol problems in a drug-dependent population. Rates of detecting alcohol problems varied widely (15-76%). The Addiction Severity Index (ASI) and the Family Alcohol and Drug Survey (FADS) yielded the highest sensitivities (96% and 83%, respectively) and specificities (94% and 92%, respectively). Since these instruments require less staff training and background education than the SCID, they offer cost-effective alternatives for efficient screening and assessment of alcohol problems in drug-dependent populations.

Adult↗
PubMed1994

Adrenocorticotropin responses following administration of ethanol and ovine corticotropin-releasing hormone in the sons of alcoholics and control subjects.

Alcoholism is a familial disorder with both genetic and environmental determinants. The sons of alcoholic fathers have been documented to have alterations in several neuroendocrine measures. We investigated the ACTH/cortisol response to ovine corticotropin-releasing hormone (oCRH) and ethanol in men with and without a family history of alcoholism. Men were defined as family history positive (FHP) (n = 7) if their father was alcoholic; as family history negative (FHN) (n = 16), if their father was nonalcoholic. Ethanol (0.75 g/kg) or placebo was ingested over 15 min, 1 microgram/kg oCRH was administered, and plasma ACTH/cortisol levels were determined at -20, 0, 15, 30, 60, and 90 min after oCRH. Following placebo, FHP men had lower peak ACTH response to oCRH than did FHN men (12 +/- 2 vs 20 +/- 2 pmol/liter, P = 0.04). In FHN men, plasma ACTH response to oCRH was blunted during the ethanol session compared to the placebo session (13 +/- 1 vs 20 +/- 2 pmol/liter; P = 0.006). In contrast, FHP men had similar ACTH responses to oCRH during ethanol and placebo sessions. Cortisol responses to oCRH were similar in both groups during both sessions. In summary, FHP and FHN nonalcoholic men had different plasma ACTH responses following the administration of oCRH.

Adrenocorticotropic Hormone↗
PubMed1994

Differential expression of guanosine triphosphate binding proteins in men at high and low risk for the future development of alcoholism.

We evaluated G-proteins that are components of adenylyl cyclase (AC) signal transduction in erythrocyte and lymphocyte membranes from 26 family history positive (FHP) non-alcoholic and 26 family history negative (FHN) nonalcoholic subjects. Subjects were classified as FHP if their father met criteria for alcohol dependence; as FHN, if there was no history of alcoholism in any first or second degree relatives. Immunoblot analysis indicated that levels of erythrocyte membrane Gs alpha from FHP subjects were greater than levels in FHN subjects (171 +/- 11 vs 100 +/- 6, P < 0.001). To confirm the results of the immunoblot analysis, Gs alpha was quantitated by cholera toxin-dependent [32P]ADP-ribosylation. Levels of erythrocyte [32P]ADP-ribose-Gs alpha from FHP subjects were greater than levels in FHN subjects (236 +/- 28 vs 100 +/- 14, P < 0.001). Gs alpha levels did not correlate with age or alcohol consumption. By contrast to differences in Gs alpha, immunoblot analysis showed similar levels of Gi(2)alpha and Gi(3)alpha in erythrocyte membranes of FHP and FHN subjects. Pertussis toxin-catalyzed [32P]ADP-ribosylation of Gi-like G-proteins confirmed the immunoblot observations. Lastly, compared to FHN subjects, FHP subjects had enhanced Gs alpha expression in lymphocyte membranes as well (138 +/- 11 vs 100 +/- 5.5; P < 0.02). In summary, compared to FHN nonalcoholic men, FHP nonalcoholic men had greater levels of the stimulatory G-protein, Gs alpha, in erythrocyte and lymphocyte membranes. Enhanced expression of Gs alpha may be a marker of increased risk for the future development of alcoholism.

Adenosine Diphosphate Ribose↗
PubMed1993

Prenatal care and drug use in pregnant women.

This case-control study tested the hypothesis that pregnant inner-city women with low utilization of prenatal care are likely to be frequent drug users. Cases registered consecutively for prenatal care at > or = 28 weeks gestation or had < 4 prenatal visits. Controls were matched to cases by date of delivery. 24/81 (30%) cases and 16/128 (12%) controls were frequent drug users (adjusted odds ratio = 2.5; 95% CI, 1.2-5.4). Drug use (P = 0.01) and socioeconomic status (P = 0.001) were significantly correlated with prenatal care utilization. Self-report alone failed to note as many drug users as toxicology screen alone. Both substance use history and toxicology screen are advisable in women with low utilization of prenatal care.

Adolescent↗
PubMed1993

Enhanced expression of the inhibitory protein Gi2 alpha and decreased activity of adenylyl cyclase in lymphocytes of abstinent alcoholics.

Ethanol exposure alters signal transduction through the adenylyl cyclase (AC) system. To elucidate the basis for this effect, we investigated the AC system in peripheral lymphocytes from abstinent alcoholic men (n = 22), actively drinking alcoholic men (n = 41), and nonalcoholic control men (n = 16). Immunoblot analysis of lymphocyte membranes from abstinent alcoholics demonstrated a 3.0-fold increase in the level of Gi2 alpha protein (p < 0.05) compared with controls. However, levels of Gs alpha protein were similar in both groups. Abstinent alcoholics had a 2.9-fold increase in Gi2 alpha mRNA (p < 0.001) and a 2.7-fold increase in Gs alpha mRNA (p < 0.03) compared with lymphocytes from control subjects. Actively drinking alcoholics, in contrast, had unaltered Gs alpha protein, Gi2 alpha protein, and Gi2 alpha mRNA levels compared with control subjects, but did have a 1.8-fold increase (p < 0.01) in Gs alpha mRNA. Consistent with enhanced Gi2 alpha expression, lymphocyte membranes from abstinent alcoholics had decreased basal, prostaglandin E1-, guanosine 5'-0-(3-thiotriphosphate)-gamma S-, and forskolin-stimulated AC activity compared with both controls and actively drinking alcoholics (p < 0.05). We conclude that lymphocyte AC is reduced during abstinence from alcohol and enhanced expression of the inhibitory G-protein, Gi2 alpha, may account for this change.

Adenylyl Cyclases↗