Development of miotic cross-tolerance between pyridostigmine and sarin vapor.

The organophosphorous nerve agent sarin (GB) and the carbamate pyridostigmine bromide (PB) both inhibit acetylcholinesterase (AChE), leading to overstimulation of muscarinic receptors. Both GB and PB produce miosis through stimulation of ocular muscarinic receptors. This study investigated 2 hypotheses: (1) that the miotic response to PB would decrease following repeated injections; and (2) that repeated administration of PB would result in tolerance to the miotic effect of GB vapor. Rats were injected intramuscularly with saline, 0.04 mg/kg, 0.5 mg/kg, or 1.4 mg/kg of PB twice daily for 8 consecutive days. After day 3, animals injected with 1.4 mg/kg PB developed miotic tolerance. Twenty-four (24) h following the final PB injection, the rats were exposed to GB vapor (4.0 mg/m(3)). A similar magnitude of miosis was observed in all groups after GB exposure. However, the rate of recovery of pupil size in animals pretreated with 0.5 and 1.4 mg/kg PB was significantly increased. Twenty (20) h following exposure to GB vapor, the pupils of animals pretreated with 1.4 mg/kg PB had recovered to 77% +/- 4% of their pre-exposure baseline, whereas the saline-injected controls had recovered to only 52% +/- 2% of their pre-exposure baseline. The increased rate of recovery does not appear to be a result of protection of pupillary muscarinic receptors by the higher doses of PB, as there was no longer PB present in the animal at the time of GB exposure. These results demonstrate the development of tolerance to the miotic effect of PB following repeated exposures, and also suggest that cross-tolerance between PB and GB occurs. However, because the magnitude of the response was not reduced, the PB pretreatment and its associated miotic cross-tolerance does not appear to diminish the effectiveness of miosis as a biomarker of acute exposure to nerve agent vapor.     

Educating African American men about the prostate cancer screening dilemma: a randomized intervention.

BACKGROUND: Until there is a definitive demonstration that early diagnosis and treatment of prostate cancer reduces disease-related mortality, it is imperative to promote informed screening decisions by providing balanced information about the potential benefits and risks of prostate cancer screening. Within a community/academic collaboration, we conducted a randomized trial of a printed booklet and a videotape that were designed for African American (AA) men. The purpose of the trial was to determine the effect of the interventions on knowledge, decisional conflict, satisfaction with the screening decision, and self-reported screening. METHODS: Participants were 238 AA men, ages 40 to 70 years, who were members of the Prince Hall Masons in Washington, DC. Men were randomly assigned to the (a) video-based information study arm, (b) print-based information study arm, or (c) wait list control study arm. Intervention materials were mailed to men at home. Assessments were conducted at baseline, 1 month, and 12 months postintervention. Multivariate analyses, including ANCOVA and logistic regression, were used to analyze group differences. RESULTS: The booklet and video resulted in a significant improvement in knowledge and a reduction in decisional conflict about prostate cancer screening, relative to the wait list control. Satisfaction with the screening decision was not affected by the interventions. Self-reported screening rates increased between the baseline and the 1-year assessment, although screening was not differentially associated with either of the interventions. In exploratory analyses, prostate-specific antigen testing at 1 year was more likely among previously screened men and was associated with having low baseline decisional conflict. CONCLUSIONS: This study represents one of the first randomized intervention trials specifically designed to address AA men's informed decision making about prostate cancer screening. We have developed and evaluated culturally sensitive, balanced, and disseminable materials that improved knowledge and reduced decisional conflict about prostate cancer screening among AA men. Due to the high incidence and mortality rates among AA men, there is a need for targeted educational materials, particularly materials that are balanced in terms of the benefits and risks of screening.     

Evolution of the sperm aster after microinjection of isolated human sperm centrosomes into meiotically mature human oocytes

This study examined the feasibility of isolating and transferringthe centrosome-containing region of spermatozoa to mature humanoocytes. The findings demonstrate that individual sperm centrosomescan be transferred and are capable of nucleating maternal tubulinto form a well-developed sperm aster in the recipient oocyte.The results are discussed with respect to centrosome functionin early human development and applications in clinical in-vitrofertilization in the treatment of certain forms of male factorinfertility.     

FETAL SCALP BLOOD SAMPLING

Fetal scalp blood sampling (FSBS), in conjunction with fetal heart rate monitoring, is a method of fetal surveillance that may avoid cesarean delivery of the healthy fetus or indicate the need for immediate delivery of a compromised fetus. Some researchers have recently begun to question the efficacy of FSBS. In this article, three nurse-midwives discuss FSBS as a tool in assessing fetal well-being during labor and consider whether FSBS is a nurse-midwifery procedure.     

Deep venous thrombosis and pulmonary embolism

All surgical patients are at risk for the development of deep venous thrombosis and subsequent pulmonary embolism or postphlebitic syndrome. The evolution of ultrasonographic imaging has increased the awareness of prevention, diagnosis, and treatment of deep venous thrombosis. Duplex imaging and Doppler color flow imaging have made the diagnosis of deep venous thrombosis relatively simple, painless, inexpensive, and definitive. These procedures have gained acceptance by both patients and physicians. Several risk factors have been identified that increase the chance of the development of deep venous thrombosis. These factors include a history of deep venous thrombosis, presence of a malignant process, increasing age, cigarette smoking, obesity, prolonged bed rest, and general anesthesia. The greater the number of risk factors, the more aggressive prophylaxis should be. Means of prophylaxis have improved, and surgeons now generally agree that some form of prophylaxis is required. Heparin and intermittent compression devices appear to be equally effective in preventing deep venous thrombosis. The addition of venous monitoring in high-risk patients permits immediate identification of the presence of deep venous thrombosis. During the last decade, the treatment of patients with deep venous thrombosis has changed little. Heparin followed by warfarin remains the treatment of choice. A small group of patients receive fibrinolytic therapy for deep venous thrombosis. Although the incidence of postoperative deep venous thrombosis has decreased during the last decade, it remains a significant complication.     

The effect of age, sex, weight and height on the plasma concentrations in healthy subjects of the acidic metabolites of some biogenic monoamines involved in psychiatric and neurological disorders.

1. The plasma concentrations of unconjugated phenylacetic acid and m-hydroxyphenylacetic acid are lower in male than in female subjects. 2. The plasma concentrations of unconjugated phenylacetic acid and mandelic acid decrease with increasing weight and height for all subjects combined. The same relationships apply for both males and females but are significant only for males. 3. Homovanillic and vanillylmandelic acid concentrations in plasma increase with age. 4. The importance of using age, sex, weight and height matched groups in studies involving the plasma concentrations of some of the trace amine metabolites in psychiatric disorders has been demonstrated. This is particularly the case for phenylacetic acid, the major metabolite of phenylethylamine which is now thought to be a neuromodulator of catecholaminergic neurotransmission.