Adolescents and Substance Abuse Testing: Consideration of treatment models

Substance abuse testing and treatment programs for adolescents using drugs are receiving increased attention on high school campuses. Many policymakers question drug testing and the treatment models for adolescent substance abusers. This paper explores the impact of drug testing. Treatment models and approaches for substance abuse are presented. It is recommended that treatment counselors explore drug testing in relationship to treatment models for substance use. We advise counselors to consider comprehensive programs for adolescents based on their belief systems and values assigned to moral, medical and social models of treatment.     

An epidemiologic study of smoking and primary infertility in women.

OBJECTIVE: To determine the relationship between cigarette smoking and primary female infertility. DESIGN: Retrospective, case-control study. SETTING: Population-based and randomly selected from eight geographic areas in the United States. PARTICIPANTS: Women, 20 to 54 years of age, who were randomly selected to serve as the control group of the Cancer and Steroid Hormone Study were used for this study. Within this group, there were 483 women who were classified as having experienced primary infertility and 2,231 women eligible to serve as controls. Primary infertility, defined as 24 consecutive months of unprotected intercourse without conception, was documented from a calendar of each women's reproductive and contraceptive history. RESULTS: Smoking one pack of cigarettes per day (odds ratio = 1.36) and starting to smoke before 18 years of age (odds ratio = 1.30) were significantly associated with increased risk of infertility. Life table and proportional hazards analysis indicated that smoking did not significantly increase the time required to conceive among infertile women. CONCLUSIONS: Number of cigarettes smoked and age when the women began smoking contributed to infertility in this study. It is reasonable, therefore, to recommend that women stop smoking when they are attempting to become pregnant.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Effect of captopril on functional mitral regurgitation in dilated heart failure: a randomised double blind placebo controlled trial.

OBJECTIVE--To determine the efficacy and dose requirements of captopril to reduce functional mitral regurgitation in patients with dilated heart failure. DESIGN--A randomised double blind placebo controlled parallel arm trial. Incremental daily doses of 25 mg, 50 mg and 100 mg captopril used for a four week period each for a total of 12 weeks preceded by a two week placebo washout. Twenty eight ambulatory patients (mean age 72) New York Heart Association (NYHA) class II or III with apparently controlled ischaemic dilated heart failure (ejection fraction 29% (0.04%)) on digoxin, diuretics, and nitrates were randomised. All had at least grade 2/4 functional mitral regurgitation (> 5 cm2 regurgitant area on colour flow Doppler). RESULTS--Twenty three patients completed the study (13 on placebo and 10 on captopril). Significant improvements were confined to the captopril group. Compared with placebo the following improvements were noted in the captopril treated group: mitral regurgitant area decreased from a threshold at 50 mg/day (p < 0.05, mean (95% confidence interval (95% CI)) 3.1 (0.2 to 6.0) cm2), with a further decrease at 100 mg/day (p < 0.01, mean (95% CI) 5.3 (3.1 to 7.5) cm2). Significant improvements in all the other measurements were noted only after 100 mg/day. Stroke volume increased (p < 0.01, mean (95% CI) 11, (1.4 to 21) ml), systemic vascular resistance decreased (p < 0.05, mean (95% CI) 414 (35 to 793) dyn s cm5), left atrial area decreased (p < 0.05, mean (95% CI) 4.3 (0.03 to 8.6) cm2), and deceleration time increased (p < 0.01, mean (95% CI) 52 ms (7 to 98) ms). Left ventricular diameter decreased marginally (p = 0.06, mean (95% CI) 4 (-0.05 to 9 mm). Duke activity index score increased (p < 0.001, median (95% CI) 6.8 (4.5 to 12) points). Heart rate, mean arterial blood pressure, serum creatinine, and serum potassium did not change with either placebo or captopril. No patient was withdrawn directly due to the side effects of captopril. In an open phase nine placebo patients given captopril in rapid increments reaching 100 mg/day in the fourth week showed similar improvements. CONCLUSION--Captopril is efficacious in reducing functional mitral regurgitation in dilated heart failure. Patients require and must tolerate high doses (50-100 mg/day) for additive effects over supervised conventional treatment to occur.     

Cell survival characteristics of a human colon adenocarcinoma cell line after photodynamic treatment: a comparison of Photofrin II and TPPS

A comparison has been made of the in vitro light-activated drug cytotoxicities of two different porphyrin compounds, Photofrin II and TPPS4. An early passage human colon adenocarcinoma cell line, WiDr, has been exposed to either drug for 24 h, the excess drug washed from the cells and the cells irradiated with light using quartz-tungsten-halogen lamps. Neither light nor drug alone under the experimental conditions employed was toxic to WiDr cells. Together, considerable cytotoxicity could be seen and the shapes of the cell survival curves following exposure to either drug then irradiation with light, were similar. For equal amounts of drug in the medium, Photofrin II was a more efficient photosensitizer of WiDr cells than TPPS4, and differences in cellular uptake could only partly explain this. When the experimental procedure was changed by reducing the temperature of irradiation, a reduction in photosensitizing efficiency could be demonstrated. This was more pronounced for Photofrin II, and was seen as a change in the slope of the final portion of the survival curve; and as a change in the shoulder for TPPS4. Two different batches of the two drugs were compared and shown to give slightly different results for Photofrin II (change in shoulder) but not to differ for TPPS4.     

Noncortical origins of the spinal motor evoked potential in rats

Motor evoked potentials (MEPs) were recorded from the spinal cord, sciatic nerve, or both during transcortical electrical stimulation in the rat. Four peaks could be consistently identified in the spinal MEP. The latency and amplitude of the peaks varied differentially with intensity and polarity of stimulation. Conduction velocity for Peak 1 of the MEP was 43 m/sec. Bilateral sciatic nerve MEPs were present after unilateral cortical stimulation. The spinal MEP was elicited by stimulation of areas outside the motor cortex, and the response persisted during subcortical stimulation and after motor cortex ablation. We present evidence suggesting that components of the spinal MEP in rats arise from pathways outside the motor cortex.     

Improved neuropsychological outcome in children with brain tumors diagnosed during infancy and treated without cranial irradiation.

Neuropsychological outcome of 28 patients with brain tumors diagnosed before the age of 36 months (mean, 19 months) was assessed using a comprehensive battery of tests. Elapsed time between diagnosis and testing averaged 6.2 years. Half the patients had received cranial radiation therapy and surgery, with and without chemotherapy, whereas the rest had received only surgery, with or without chemotherapy. Groups were comparable with respect to tumor diagnosis and location, age at diagnosis, race, and sex. Intellectual functioning was significantly lower in children whose treatment included cranial irradiation than in those treated without cranial irradiation, and this effect was more pronounced in nonverbal than in verbal intellectual abilities. Mean scores for the radiation group were lower than for the no-radiation group in all areas assessed and were significantly below age-based normative means in five of the eight cognitive areas: intellectual, memory, attention, motor, and visual-spatial skills. Mean scores for children in the no-radiation group were generally within the average range in all cognitive areas except visual-spatial skills, which were significantly below age-based normative means. Endocrine deficiencies and growth retardation were much more prevalent in patients treated with cranial irradiation. Because the immature brain is susceptible to treatment-related pathologic changes, infants are at greater risk than older children for significant, long-term neuropsychological, endocrine, and growth sequelae. In children treated without cranial irradiation, morbidity was minimized without an increased rate of mortality.     

Solid-phase extraction of drugs from biological tissues--a review.

Solid-phase extraction procedures are being used increasingly in all types of drug testing laboratories, including those which carry out forensic toxicology. The advantages of such procedures include decreased operator time, reduced solvent volumes, and increased extraction efficiency. The application of existing techniques, however, has not yet been applied to tissues that are widely available postmortem. Tissue analysis can make the task of interpretation of drug levels much easier, particularly where unstable drugs are involved (e.g., cocaine). This review article explores the possibilities of applying existing extraction procedures to human tissue samples. We also consider the reasons why forensic laboratories have been slow to investigate such possibilities. We hope to stimulate interest in alternative tissue extraction procedures by reviewing reported procedures that apply to both human and animal tissue.     

Development of a fetal circadian rhythm after disruption of the maternal circadian system

The role of maternal circadian rhythms in the development of the fetal circadian system was investigated in the rat. Pregnant females were subjected to procedures known to disrupt circadian function, ablation of the maternal suprachiasmatic nuclei (SCN) or housing in constant illumination, on gestational day 10. Circadian function was assessed in fetuses at gestational day 22 by analysis of glucose utilization in hypothalamic slices in vitro using the 2-deoxyglucose method. Fetuses from control females exhibit a robust rhythm in glucose utilization in the SCN. In contrast, the SCN of fetuses from females with SCN lesions, or housed in constant illumination, show no significant day-night difference in glucose utilization. Analysis of individual brains indicates, however, that this apparent disruption in the development of circadian rhythmicity in metabolism in the fetal SCN is due to a desynchronization of individual fetuses resulting from the loss of maternal entraining influences. Thus, the fetal SCN is capable of developing a circadian rhythm in glucose utilization independent of the maternal circadian system.