PubMed Health⌕ Search

Biomedical subjects

S K Teoh

Publications and source records attributed to S K Teoh.

At least 19 recordsLinked to original sources
PubMed1998

Cocaine tolerance: behavioral, cardiovascular, and neuroendocrine function in men.

Cocaine tolerance was assessed by comparing the acute effects of cocaine in drug-abstinent men who reported occasional cocaine use (n = 6) and in men who met DSM-III-R diagnostic criteria for dependence on both cocaine and opiates (n = 6). Peak plasma cocaine levels were equivalent in the two groups, and pharmacokinetic analyses revealed no significant differences in cocaine levels at any time. Cocaine induced a significantly greater increase in ACTH in the occasional cocaine users than in the cocaine dependent men (p < .01). Heart rate and systolic and diastolic blood pressure increases after cocaine were also significantly greater in the occasional cocaine users than in the cocaine-dependent men (p < .05). These neuroendocrine and physiologic differences were paralleled by significantly greater subjective reports of "high" and "euphoria" by the occasional cocaine users (p < .03 to .0001). These data are consistent with the conclusion that tolerance to cocaine's physiologic, neuroendocrine, and subjective effects may occur as a function of chronic use.

Adrenocorticotropic Hormone↗
PubMed1996

Effects of alcohol ingestion on estrogens in postmenopausal women.

OBJECTIVE: To determine if moderate alcohol drinking increases circulating estradiol levels in postmenopausal women who are taking estrogen replacement. DESIGN: Randomized, double-blind, placebo-controlled crossover study of the effects of alcohol ingestion on plasma estradiol and estrone. SETTING: Inpatient Clinical Research Center. PARTICIPANTS: Twelve healthy postmenopausal women receiving oral estrogen (estradiol, 1 mg/day) and progestin (medroxyprogesterone acetate) replacement therapy were compared with 12 postmenopausal women who were not using estrogen replacement therapy (ERT). INTERVENTION: Each group drank alcohol (0.7 g/kg) and an isoenergetic (isocaloric) placebo (randomized sequence) on consecutive days. Women who were taking ERT were studied during the estrogen-only portion of their replacement cycle, and estrogen was administered each evening at 2100 hours. MAIN OUTCOME MEASURE: The impact of alcohol ingestion on plasma estradiol and estrone levels. RESULTS: Alcohol ingestion lead to a 3-fold increase in circulating estradiol in women on ERT; however, alcohol did not change estradiol significantly in control women who were not on ERT. In women using ERT, estradiol levels increased from 297 to 973 pmol/L (81 to 265 pg/mL) within 50 minutes (P<.001) during the ascending limb of the blood alcohol curve and remained significantly above baseline for 5 hours (P<.001). No significant increase in circulating estrone was detected in either group. However, estrone levels decreased after alcohol and placebo in women on ERT (P<.05). Blood alcohol levels did not differ significantly in women who used ERT and those who did not. Peak blood alcohol levels of 21 mmol/L were attained in each of the 2 groups within 50 to 60 minutes after drinking began. Changes in estradiol were significantly correlated with changes in blood alcohol levels on both the ascending (P<.001) and descending (P<.001) limb of the blood alcohol curve. CONCLUSIONS: Acute alcohol ingestion may lead to significant and sustained elevations in circulating estradiol to levels 300% higher than those targeted in clinical use of ERT. Potential health risks and benefits of the interactions between acute alcohol ingestion and ERT should be further evaluated.

Alcohol Drinking↗
PubMed1996

Brain alcohol detectability increase with repeated administration in humans: a proton spectroscopy study.

Proton MRS was used to detect brain alcohol after repeated alcohol exposure in human subjects. MRS detectability measurements were made after administration of an alcoholic drink (0.6 g/kg alcohol) and after an identical drink administrated 6 h later. Between-drink differences in the methyl proton triplet resonance of ethyl alcohol were assessed at statistically equivalent and near-peak blood alcohol concentrations (reflecting brain alcohol concentrations) and statistically equivalent internal standard N-acetyl resonance areas after Drinks 1 and 2, respectively. Brain alcohol detectability was not altered in TE 30-ms spectra but was increased in all five subjects after Drink 2 by an average of 70% in TE 270-ms spectra (p < 0.01). This was accompanied by significant between-drink differences in subjective ratings of alcohol's effects, suggestive of induction of acute alcohol tolerance. These findings suggest increased brain alcohol detectability in TE 270-ms spectra after repeated alcohol exposure that may reflect acute alcohol tolerance.

Adult↗
PubMed1995

Improved regional cerebral blood flow in chronic cocaine polydrug users treated with buprenorphine.

UNLABELLED: Chronic cocaine and polydrug abuse have been associated with regional abnormalities in cerebral perfusion. The authors have previously demonstrated that these abnormalities are partially reversible after drug addiction treatment with buprenorphine. This study was designed to separate the effect on cerebral perfusion of abstinence from drug use from that of buprenorphine directly. METHODS: Fifteen cocaine- and heroin-dependent men were studied with 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain SPECT. The men, all part of an inpatient drug abuse treatment research program, were randomly assigned after detoxification to receive placebo or either 6 or 12 mg daily buprenorphine treatment. SPECT studies were performed at baseline, after maximum dosage was reached and after tapering off the study drug. Studies were compared visually with regard to the number and location of perfusion defects by reviewers blinded to treatment assignment. RESULTS: Subjects receiving buprenorphine had a significant reduction in the number of defects per study between baseline and maximum buprenorphine dose as compared with those receiving placebo (decrease of 4 +/- 5.4 versus increase of 4.8 +/- 4.7, p = 0.006). These differences were dose-related. Improvement with buprenorphine was temporary, with return to baseline after tapering off. CONCLUSION: Buprenorphine treatment, and not abstinence from drug use alone, leads to improvement in regional cerebral perfusion abnormalities in chronic cocaine- and heroin-dependent men.

Adult↗
PubMed1994

In vivo proton magnetic resonance spectroscopy detection of human alcohol tolerance.

Alcohol tolerance was ascertained with in vivo proton magnetic resonance spectroscopy (MRS) in men who regularly consumed either large (10-20 drinks/week) or small (2-4 drinks/weeks) amounts of beverage alcohol. Brain ethanol concentrations were determined by MRS, and blood ethanol levels were measured by gas chromatography after controlled ethanol administration (0.8 g/kg). Brain-blood ethanol concentration ratios for heavy drinkers were significantly greater than ratios for occasional drinkers (P < 0.002). Inasmuch as ethanol tolerance covaries with the severity of dependence, MRS procedures may facilitate our understanding of alcohol tolerance and treatment of alcoholism.

Adult↗
PubMed1994

Divided attention task performance and subjective effects following alcohol and placebo: differences between women with and without a family history of alcoholism.

Women with (FHP) and without (FHN) family histories of alcoholism received either 0.56 g/kg alcohol or an isocaloric placebo in a repeated measures group design. Subjects performed a divided attention task and gave subjective ratings of 12 alcohol effects over a 3-h interval. After comparable doses of alcohol, 7 FHP and 10 FHN women had comparable ascending (blood alcohol levels) BALs. BALs peaked earlier for FHP women and then steadily declined. FHP women had a concomitant increase in visual search response times 30 min after alcohol. In contrast, scores on a simultaneously presented compensatory tracking task were virtually identical for the 7 FHP and 10 FHN women after alcohol and for the 8 FHP and 10 FHN women after placebo. After alcohol the FHP and FHN women had 7 out of 12 significantly different subjective ratings of alcohol responses. FHP women had lower subjective responses to alcohol and lower BALs, but their subjective responses were more strongly correlated with BALs. Our findings for women studied in a group design confirm the lower magnitude of subjective responses reported for pair-matched FHP men following comparable doses of alcohol in within-subjects and between-subjects designs in other laboratories.

Adult↗
PubMed1994

Effects of dopamine on prolactin: interactions with cocaine self-administration by female rhesus monkeys.

The effects of dopamine on regulation of prolactin secretion were studied in female rhesus monkeys before cocaine exposure and again after 2 months to 2.7 years of daily cocaine self-administration. During chronic cocaine exposure, basal prolactin levels increased by 227 to 350% above drug-free control levels (P < .05). On each endocrine study day, three successive 80-min dopamine infusions (10 micrograms/kg/min i.v.) were alternated with 20-min interruptions of dopamine infusions to assess the degree of prolactin suppression and the magnitude of postdopamine prolactin increases. Dopamine significantly reduced prolactin below base-line levels within 60 to 80 min under all conditions (P < .05-.01). In four drug-naive follicular phase females, postdopamine increases in prolactin never exceeded predopamine base-line levels of 6.2 (+/- 1.8) ng/ml. After an average of 74 days of cocaine self-administration [3.7 (+/- 0.11) mg/kg/day], the postdopamine prolactin increases were significantly higher than during drug-free control conditions (P < .01) and reached hyperprolactinemic levels of 57.6 ng/ml. After an average of 300 days of cocaine self-administration [6.5 (+/- 0.06) mg/kg/day], postdopamine prolactin increases peaked at 339% above predopamine basal prolactin levels. After an average of 433 days of cocaine self-administration [6.45 (+/- 0.08) mg/kg/day] postdopamine prolactin increases remained significantly higher (P < .01) than during drug-free conditions. A similar pattern of postdopamine prolactin increases to hyperprolactinemic levels (ranging from 44.5 to 141.2 ng/ml) also were measured in two other females studied after 19 to 20 months of cocaine self-administration [6.21 (+/- 0.11) and 7.49 (+/- 0.17) mg/kg/day]. After 2.7 years of cocaine self-administration, one monkey developed persistent hyperprolactinemia and basal prolactin levels averaged 326 ng/ml after 89 days of cocaine abstinence. These data suggest that the prolactin secretory response to dopamine perturbation may provide a sensitive index of changes in dopaminergic regulation of prolactin during chronic cocaine exposure.

Animals↗
PubMed1994

Cocaine effects on pulsatile secretion of ACTH in men.

The effects of cocaine on pulsatile secretion of adrenocorticotropic hormone (ACTH) in men were studied under controlled clinical research ward conditions. Eight men with a Diagnostic and Statistical Manual of the American Psychiatric Association Version III, revised, diagnosis of concurrent cocaine and opioid dependence provided their informed consent for participation in this study. After an overnight fast, a challenge dose of cocaine (30 mg i.v.) or placebo was administered under single-blind conditions in a randomized order on 2 study days. Blood samples were collected at 2-min intervals for 76 min during base line and for an additional 76 min after i.v. administration of the challenge dose. Peak plasma cocaine levels of 313.8 +/- 46.5 ng/ml were detected within 2 min after cocaine administration. The cluster analysis program originally described by Veldhuis and Johnson (1986) was used to characterize ACTH pulsatile secretion (Iranmanesh et al., 1990). Acute cocaine administration (30 mg i.v.) significantly increased ACTH mean peak amplitude (P < .05), mean percent increase in peak amplitude, (P < .05), mean peak area (P < .04), total peak area (P < .04) and incremental peak height (P < .04). Mean ACTH valley levels (P < .02) and mean valley nadir (P < .02) were also significantly increased after cocaine administration. We postulate that cocaine stimulates the release of corticotropin releasing factor and that the cocaine-induced secretion of corticotropin releasing factor increases the amplitude of ACTH pulses, because ACTH pulse frequency was not altered by cocaine.

Adrenocorticotropic Hormone↗
PubMed1994

Gender differences in cerebral perfusion in cocaine abuse: technetium-99m-HMPAO SPECT study of drug-abusing women.

UNLABELLED: Cocaine abuse continues to be a major public health concern, with a variety of medical and neurologic sequelae. Previous studies have demonstrated abnormalities in cerebral perfusion in chronic cocaine abusers and after acute administration of cocaine. Although women are becoming increasingly represented among drug abusers, few studies have included women. To the authors' knowledge, none has compared cerebral perfusion in asymptomatic women with that in men. METHODS: The cerebral perfusion of 13 cocaine-dependent women, 4 of whom were also heroin dependent, was studied with 99mTc hexamethylpropyleneamine oxime (HMPAO) SPECT. These women were compared with 13 cocaine-dependent men and 26 healthy control subjects. Structural brain lesions and neurologic abnormalities were excluded by MRI and neurologic evaluation. Perfusion studies were interpreted in a standardized fashion by reviewers blinded to clinical information. RESULTS: It was found that cocaine-dependent women were much less likely to have abnormal study findings than cocaine-dependent men (p = 0.003) and were indistinguishable from normal women (p = 1.0). However, the results in both women and men who concurrently used heroin plus cocaine were all abnormal. Perfusion abnormalities tended to be located in anterior brain structures, such as the frontal and temporal cortex and the basal ganglia. CONCLUSION: These data suggest that cocaine-dependent women have fewer abnormalities in cerebral perfusion than cocaine-dependent men, but that concurrent abuse of heroin and cocaine is associated with more perfusion abnormalities in both sexes.

Adult↗
PubMed1994

Buprenorphine effects on morphine- and cocaine-induced subjective responses by drug-dependent men.

The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on reports of subjective effects after single intravenous doses of morphine (10 mg), cocaine (30 mg), and saline placebo were studied on an inpatient clinical research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III-R). Latency to detection and certainty of a drug effect, as well as drug quality (intensity, euphoria, and dysphoria), were studied before and after 10 to 12 days of buprenorphine maintenance. Saline was accurately identified by all 26 patients during the drugfree baseline and by 25 patients during buprenorphine maintenance conditions. All patients accurately identified morphine during the drugfree period before treatment with buprenorphine, but 18 (69%) of 26 patients were unable to detect morphine during buprenorphine maintenance and 2 misidentified morphine as cocaine. Six men (23%) accurately identified morphine and reported that the intensity and quality of morphine's effects were equivalent to drugfree conditions. Cocaine levels in plasma 5 minutes after intravenous cocaine injection were equivalent before and during buprenorphine treatment and averaged 282.8 +/- 43.6 and 295.2 +/- 28.8 ng/ml during 4 and 8 mg/day of buprenorphine maintenance, respectively. All patients accurately identified cocaine before and during buprenorphine maintenance, and there were no significant changes in latency to detection and certainty of a drug effect or reports of cocaine-induced intensity or euphoria during buprenorphine treatment. The concordance between responses to morphine and cocaine during inpatient buprenorphine maintenance and drug use during the first 4 weeks of outpatient buprenorphine treatment was also examined in 16 men. The effects of buprenorphine on individual responses to an acute intravenous dose of morphine or cocaine during the inpatient study did not reliably predict the frequency of heroin or cocaine self-administration during the first 4 weeks of daily outpatient buprenorphine maintenance.

Administration, Sublingual↗
PubMed1993

A nonferrous instrumental joystick device for recording behavioral responses during magnetic resonance imaging and spectroscopy.

A nonferrous joystick device was developed to permit subjects to continuously report ethanol-induced alterations in subjective mood states while undergoing a magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) procedure. The device utilizes air pressure (supplied by a small compressor) that is directed to a series of tubes that terminate in a hand-held unit. The hand-held unit easily fits inside the magnet and resembles a standard computer game joystick except that the ends of the air hoses replace the buttons. The control unit contains three pressure transducers, which are triggered when the tubes are occluded by the subject, activating different pens on an event marker located 6 m from the whole body imager. The unit is safe to use inside a 1.5-Tesla magnetic field and does not disrupt the MRI and MRS recording procedures. Subjective reports of ethanol-induced euphoria and intoxication paralleled the MRS detection of ethanol in the brain. This device could prove to be useful in numerous behavioral studies involving whole-body MRI and MRS.

Adult↗
PubMed1993

Pituitary volume in men with concurrent heroin and cocaine dependence.

Pituitary gland volume was measured in 16 men between the ages of 26-33 with magnetic resonance imaging. Eight male patients had a Diagnostic and Statistical Manual III-Revised, American Psychiatric Association Axis I diagnosis of concurrent opioid and cocaine dependence. The average duration of opioid and cocaine abuse was 7.8 +/- 2.0 and 6.9 +/- 1.4 yr, respectively. All patients were in good physical health as determined by physical examination, blood chemistry, hemogram and hormone analysis, and all tested negatively for the HIV antibody. No patient had any other Diagnostic and Statistical Manual III-Revised Axis I diagnosis or neurological disorder. Eight healthy males served as age-matched control subjects. None of the control subjects had any past or current history of substance abuse or any clinical indication for magnetic resonance imaging. Opioid and cocaine dependent men had significantly larger pituitary gland volumes (730.0 +/- 24.4 mm3) than control subjects (540.0 +/- 26.6 mm3) (P < 0.01). The significant increase in pituitary gland volume in men who abuse opiates and cocaine may be antecedent to detection of abnormal anterior pituitary hormone function.

Adult↗
PubMed1993

Acute interactions of buprenorphine with intravenous cocaine and morphine: an investigational new drug phase I safety evaluation.

Recent preclinical and clinical studies suggest that buprenorphine, an opioid mixed agonist-antagonist, may be useful for the treatment of dual dependence on cocaine and opiates. This report describes an inpatient clinical evaluation of the safety of buprenorphine alone and in combination with single doses of cocaine and morphine. Twenty subjects with a DSM-III-R diagnosis of concurrent cocaine and opioid dependence were randomly assigned to maintenance treatment with single daily doses of 4 or 8 mg of sublingual buprenorphine for 21 days. Side effects and vital signs were evaluated every day once every 8 hours and for 2 hours after daily buprenorphine administration. The physiologic effects of a single-blind challenge dose of cocaine (30 mg intravenously), morphine (10 mg intravenously), and intravenous saline placebo were measured before and during buprenorphine maintenance. Before buprenorphine maintenance, subjects underwent methadone detoxification followed by a 9-day drug-free period. Three baseline single-blind challenge dose studies were conducted on study days 7, 8, and 9 during the drug-free period. Cardiovascular responses to cocaine and to morphine were equivalent under drug-free and buprenorphine maintenance conditions. Respiration and temperature changes in response to cocaine were also equivalent before and during buprenorphine maintenance. Respiratory rates were slightly lower after morphine administration during maintenance on 8 mg of buprenorphine, but this was not statistically significant. Mild opioid agonist-like side effects were reported during buprenorphine induction and maintenance. These included headache, sedation, nasal discharge, abdominal discomfort, and anxiety. Most opioid agonist side effects decreased within 12 to 14 days. An electrocardiogram and blood chemistry measures were normal before and during buprenorphine maintenance. These data suggest that daily maintenance on buprenorphine is not associated with adverse side effects or toxic interactions with a single acute dose of intravenous cocaine or morphine.

Administration, Sublingual↗
PubMed1993

Regional cerebral blood flow improves with treatment in chronic cocaine polydrug users.

Brain perfusion is abnormal in chronic cocaine users. To determine whether these perfusion abnormalities are reversible following treatment, we studied 10 cocaine-dependent polydrug users with 99mTc-HMPAO SPECT 2 to 3 days after admission to an inpatient treatment facility and at 7 to 8 days and 17 to 29 days after abstinence from drugs. The patients also received buprenorphine, an opioid mixed agonist-antagonist, beginning 10 days after admission and continuing to the end of the study. Imaging began 10-15 min after injection of 99mTc-HMPAO (20 mCi) using an annular gamma camera system. MRI was performed during hospitalization using a 1.5 Tesla system. SPECT and MRI were merged and five axial SPECT slices centered at the level of the basal ganglia were selected for analysis. Activity ratios were derived for cortical regions relative to cerebellar activity and were corrected for linearity with respect to regional cerebral blood flow. The cortical regions were classified as abnormal (activity ratio < 0.6), borderline (0.6-0.72) and normal (> 0.72) based on the results of the first SPECT study. In abnormal zones, regional cerebral blood flow (rCBF) increased 11.0% +/- 9.0% at 7 to 8 days and 23.8% +/- 9.4% at 17 to 29 days after initiation of treatment. The increase in rCBF was 4.8% +/- 7.1% (7 to 8 days) and 11.1% +/- 8.0% (17 to 29 days) in borderline cortex and decreased 2.9% +/- 6.3% (7 to 8 days) and increased only 2.7% +/- 13.4% (17 to 29 days) in normal cortex. The increase in rCBF did not vary significantly by location. The perfusion defects observed in chronic cocaine polydrug users are partially reversible with short-term abstinence and buprenorphine treatment.

Adult↗