Non-prescribed drug use during methadone treatment by clinic- and community-based patients

We investigated the efficacy of methadone maintenance treatment in clinic-based (n= 10) and community-based (n= 10) patients by studying the relationships between dose, plasma concentrations of methadone and non-prescribed drug-use using logistic regression. We found that clinic-based patients had significantly reduced odds of having a urine sample test positive for illicit drugs when compared to community-based patients (OR = 0.20; 95% confidence interval 0.10–0.38: p < 0.001). There was no relationship between either methadone dose or plasma methadone concentration and testing positive for non-prescribed drugs (including cocaine, cannabis, amphetamine, ecstasy, benzodiazepines). We looked specifically at the misuse of opiate drugs. Location was again important and clinic-based patients had significantly reduced odds of having a urine sample test positive for opiate drugs (OR= 0.36, 95% confidence internal 0.13–0.71: p～0.004). Opiate drug use in our patients was also significantly related to plasma methadone concentration, increasing noticeably when the drug concentration < 0.48 nmol/L (p～0.04). We found no relationship between methadone dose and odds of having a positive urine drug test in either clinic- or community-based patients.     

FENTANYL-DROPERIDOL SUPPLEMENTATION OF RAPID SEQUENCE INDUCTION IN THE PRESENCE OF SEVERE PREGNANCY-INDUCED AND PREGNANCY-AGGRAVATED HYPERTENSION

Twenty-six patients manifesting severe pregnancy-induced (PIH)or pregnancy-aggravated (PAH) hypertension who presented foremergency Caesarean section under general anaesthesia were studied.All patients came from a previously identified high risk group—namely> 25 yr, multiparous and with diastolic arterial pressuressustained at > 120 mm Hg. Our standard accelerated inductiontechnique for the management of severely hypertensive motherswas modified to include the use of fentanyl and droperidol beforeinduction. This modification of the induction sequence produceda clinically significant amelioration of the reflex sympathetichypertensive response to laryngoscopy and intubation in mostmothers receiving antihypertensive therapy, without apparentdeleterious effect in the immediate postoperative period tothose neonates unaffected by intrauterine asphyxia. ^*Present addresses: Shackleton Department of Anaesthetics, LevelE, Centre Block, Southampton General Hospital, Southampton SO94XY. University Department of Anaesthesia, Queens Medical Centre,University of Nottingham, Nottingham.     

A Modified Spectrophotometric Method Appropriate for Measuring Cholinesterase Activity in Tissue from Carbaryl-Treated Animals

Inhibited cholinesterase in tissues of animals exposed to carbamatepesticides is known to reactivate readily, presenting considerableproblems in the accurate assessment of cholinesterase activityin these tissues. Decarbamylation of cholinesterase is favoredwhen the tissue samples are diluted and/or are incubated foran extended time. The present study was performed to identifymodifications of the commonly used spectrophotometric assayfor cholinesterase activity that would minimize spontaneousreactivation of enzyme activity. Those modifications includedpreincubation of concentrated tissue with concentrated chromogen(i.e., DTNB), dilution to final reaction volume immediatelybefore measurement, and measurement of cholinesterase over ashort period of time (5–10 min). The Ellman assay withand without modifications was performed using a microtiter platereader on tissues from carbaryl-treated rats: undiluted plasma,diluted erythrocytes (1:25), minimally diluted erythrocytes(1:2), diluted brain (1:100), or minimally diluted brain (1:2).The results were compared to cholinesterase activities obtainedusing a radiometnic method which employs minimally diluted tissueand short incubation times. The degree of cholinesterase inhibitionfor undiluted or minimally diluted tissue assayed by the modifiedmethod agreed with those obtained using the radiometric method.Even if the tissues were diluted immediately before assay, however,significant reactivation occurred by the time the first measurementswere made by the conventional method. Furthermore, significantspontaneous reactivation may still occur using the modifiedmethod if the assay is run for more than 10 min. Use of thismodified Ellman method will enable more accurate estimationof in vivo cholinesterase activity in animals treated with carbamates.     

Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells

Cytokine-induced killer (CIK) cells are non-major histocompatibility complex-restricted cytotoxic cells generated by incubation of peripheral blood lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1, and interferon-gamma. Cells with the greatest effector function in CIK cultures coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by MoAbs directed against the cell surface protein leukocyte function associated antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic cytotoxic granule contents to the extracellular space upon stimulation with anti-CD3 MoAbs or susceptible target cells. Maximal granule release was observed from the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are lytic to target cells. Treatment of the effector cells with a cell-permeable analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and target cell- induced degranulation and cytotoxicity of CIK cells. The immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3- mediated degranulation, but did not affect cytotoxicity of CIK cells against tumor target cells. In addition, degranulation induced by target cells was unaffected by CsA and FK506. Our results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP- sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be- identified target cell surface molecules.     

Interval between insulin injection and breakfast in diabetes

The relationship between the insulin-breakfast interval, postprandial increase in blood glucose, and glycaemic control was studied in 58 children with diabetes. Patients recorded insulin-breakfast intervals in a home diary over a seven day period, and during a 24 hour period at the weekend provided eight serial capillary dried blood spots for glucose analysis. The highest mean blood glucose value occurred two hours after breakfast and showed a significant correlation with fructosamine concentrations. Weekend insulin-breakfast intervals ranged from 2-30 minutes, with 70% reporting intervals of less than 15 minutes. There was a significant correlation between the weekend insulin-breakfast interval and the after breakfast increase in blood glucose with a mean increment of 0.4 mmol/l in the 30 minute group and 7.2 mmol/l in the 2 minute group. Over the whole study period, children with mean insulin-breakfast intervals of two to 12 minutes had a mean fructosamine concentration of 376 mumol/l compared with 341 mumol/l in those with intervals of 15-35 minutes. This study has shown that the interval between insulin injection and breakfast significantly influences the morning postprandial rise in blood glucose and consequently short term glycaemic control. It is therefore important that patients are encouraged to leave an interval of about 30 minutes between insulin injection and breakfast.     

The consistency of family and peer influences on the development of substance use in adolescence

Latent growth modeling (LGM) was used to analyse longitudinal data for adolescent substance use from five overlapping age cohorts (11, 12, 13, 14 and 15 years at first assessment) measured at four annual time points. An associative cohort-sequential model was tested for alcohol, cigarette and marijuana use with a sample of 345 adolescents (11–18 years old) from an urban area in the Pacific Northwestern region of the United Stales. Hypotheses concerning the shape of the growth curve, the extent of individual differences in the common trajectory over time, and the influence of family cohesion, peer encouragement and gender on initial substance use and shape of the growth curve were tested. Results indicated similarities between alcohol, cigarette and marijuana initial use and development, with peer encouragement and family cohesion predictive of initial levels of use, and changes in peer encouragement influencing the developmental trajectories of the three substances. Females were higher than males in initial status and developed less rapidly in their use of the substances than did males. Findings are discussed in terms of the similarities and differences in the developmental trajectories of the three substances and the importance of family and peer influences on these trends.