Lack of effect of the calcium antagonist isradipine on cyclosporine pharmacokinetics in renal transplant patients.

Hypertension has emerged as a frequent side effect in transplant recipients on effective doses of cyclosporine (CsA). To control hypertension in renal transplant patients, calcium channel blockers have been used; some of these, however, have been shown to cause significant increases in CsA levels. These findings point out that possible interactions of each calcium antagonist with CsA deserve investigation. We performed an open, placebo-controlled study in 12 stable renal transplant recipients to determine whether short-term isradipine influences CsA pharmacokinetics. All patients had mild to moderate hypertension and received triple immunosuppressive therapy with CsA, azathioprine, and prednisolone. Throughout a 4-week period of isradipine treatment, blood CsA levels (specific and nonspecific monoclonal antibodies) remained stable. The mean trough specific level was 121 +/- 14 micrograms/L following placebo, compared to 120 +/- 14 micrograms/L during isradipine. Corresponding non-specific values were 465 +/- 68 and 474 +/- 63 micrograms/L. Also, values for Cmax, AUC, and t1/2 were not significantly changed following 4 weeks of isradipine. Mean arterial pressure was significantly reduced at the end of the study. This study implies that isradipine does not influence CsA metabolism. Further studies should be carried out to determine its long-term effects on CsA pharmacokinetics and renal function in transplanted patients.     

Regulatory control of indoor Rn

Regulation of indoor Rn is explored in the context of cost-effectiveness of regulatory action. Evaluation of cost (i.e., mitigation expenses) and benefits (i.e., savings associated with medical expenses and lost productivity related to lung cancer) at various action levels indicate that regulatory programs would be economically inefficient and unreasonable if standards were established at or below the current EPA action guide (150 Bq m-3 or less). For the approximately 95% of U.S. homes with Rn levels near or below 150 Bq m-3, government programs should continue to focus on public information and consumer protection. For the small number of homes with high Rn levels, government programs should focus on identifying high risk homes and encouraging homeowners to reduce Rn levels. Because of the potential for substantial risk reduction, such efforts would be cost-effective in these homes.     

A general multiple-compartment model for the transport of trace elements through animals.

Multiple-compartment models employed in the analysis of trace element transport in animals are often based on linear differential equations which relate the rate of change of contaminant (or contaminant concentration) in each compartment to the amount of contaminant (or contaminant concentration) in every other compartment in the system. This has the serious disadvantage of mixing intrinsic physiological properties with the geometry of the animal. The basic equations on which the model presented here is developed are derived from the actual physical process under way and are capable of separating intrinsic physiological properties from geometry. It is thus expected that rate coefficients determined through this model will be applicable to a wider category of physiologically similar animals. A specific application of the model for the study of contamination of sheep--or indeed for any ruminant--is presented, and the temporal evolution of contaminant concentration in the various compartments of the animal is calculated. The application of this model to a system of compartments with changing geometry is also presented.     

Dioxin treatment of rats results in increased in vitro induction of sister chromatid exchanges by alpha-naphthoflavone: an animal model for human exposure to halogenated aromatics

Recent reports have shown that alpha-naphthoflavone (alpha-NF) in vivo enhances the sister chromatid exchange (SCE) frequency in lymphocytes from human populations exposed to cigarette smoke or polychlorinated biphenyls and dibenzofurans. In this study, female Sprague-Dawley rats (9-11 weeks old) were administered a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and killed 6 days after treatment. Blood cultures were established with or without alpha-NF. The baseline and alpha-NF-induced SCE frequencies were assessed in lymphocytes after a 72-hr culture period. No effect on the SCE baseline frequency (cultures without alpha-NF) was detected in rats exposed to 0-30 micrograms TCDD/kg. However, the SCE frequencies from cultures incubated in the presence of alpha-NF were significantly higher in lymphocytes from rats treated with TCDD. Moreover, delta SCE values (SCE alpha-NF minus SCE baseline) were significantly higher in lymphocytes from rats treated with TCDD than in controls. A dose-dependent increase in delta SCE values was observed between 0 and 3 micrograms TCDD/kg, followed by a plateau at higher doses. This induction pattern closely resembled the induction of the liver microsomal aryl hydrocarbon hydroxylase activity by TCDD. In contrast to TCDD, phenobarbital treatment of rats (75 mg/kg/day) had no effect on alpha-NF-induced SCE frequencies in lymphocytes. Liver microsomes from TCDD-treated rats metabolized alpha-NF at a rate much faster than that of control microsomes. These studies indicate that TCDD-exposed rats provide a useful model to investigate the mechanism of enhanced in vitro induction of SCE frequency in lymphocytes from humans exposed to toxic halogenated aromatics or cigarette smoke.     

Monitoring of intracellular Ca2+ elevation in a single neural cell using a fluorescence microscope/video-camera system

For monitoring the changes in intracellular free Ca2+ concentration ([Ca2+]i), we developed a simple system combining a fluorescence microscope, an image intensifier, a video-camera, a cathode ray tube display and a photodiode, employing quin2 as a Ca2+ indicator. We recorded increases of the fluorescence intensity due to [Ca2+]i rises, when high K+ medium, neurotransmitter and Ca2+ ionophore were applied to the single cells of nervous system origin in culture. The present system is capable of simultaneous detection of the [Ca2+]i changes from multiple separate cells.     

Pharmacological properties of MO-8282, a novel antidepressant

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.     

The role of gender in an obstetrics and gynecology residency program

A brief historical review of the role of female medical students and female physicians in American medicine is presented. The 1985-1986 Council on Resident Education in Obstetrics and Gynecology Residency Data Bank was analyzed for gender distribution. Questionnaire studies were undertaken to study the possible effect of the increasing number of female residents in an obstetrics and gynecology residency program. Queries were sent to current and former residents, the attending staff, and the nursing and anesthesiology staffs. In order to evaluate the national scene, letters were mailed to directors of programs with 20 or more residents. The overall results indicated female residents have a positive effect on residency training.     

Endoscopic placement of feeding tubes in the critically ill patient

Placement of the nasojejunal feeding tube under direct visual guidance using endoscopy offers an alternative method to those currently used. We found it to be a safe method easily performed by house staff. It is less burdensome than other described endoscopic techniques and does not require patient transfer or fluoroscopic facilities.     

Rhinitis Symptom Utility Index (RSUI) in Chinese Subjects: A Multiattribute Patient-preference Approach

Background: The Rhinitis Symptom Utility Index (RSUI), originally developed in the United States, consists of a patient-preference weighting scheme and a 10-item questionnaire measuring the severity and frequency of rhinitis related symptoms over a 14-day period. This study aimed to determine whether the Chinese RSUI could adopt the US-based multi-attribute utility function (MAUF) in scoring rhinitis symptoms. Methods: In a Hong Kong study, 116 Chinese adults with allergic rhinitis completed the RSUI questionnaire and 36-item Short-Form Health Survey (SF-36) after they had been seen by two otorhinolaryngologists for disease-severity ratings. Respondents then completed computer-administered direct preference measures, i.e., visual analogue scale (VAS) and standard gamble (SG) assessments. The VAS and SG data were used to estimate a MAUF for the Chinese-based RSUI. Results: The derived MAUF was somewhat different than the one developed for the US RSUI. Test–retest reliability for the Chinese RSUI was satisfactory (ICC = 0.71, p<0.001). Scores differentiated among cases with mild, moderate, and severe symptoms (p<0.001); and between those who did and did not require medications to control symptoms (p = 0.031). Findings were significantly correlated with SF-36 domain scores (r = 0.19 to 0.37; p=0.041 to <0.001). When the US-based scoring function was applied to the Chinese subjects, the resulting mean RSUI score was significantly lower (p<0.001). Comparisons between directly measured VAS and SG scores between the US and Chinese samples, demonstrated significant differences (all p<0.05), with the US subjects consistently rating rhinitis symptoms as worse than Chinese subjects. Conclusions: The Chinese RSUI has good measurement properties that reflect patient preferences from the Chinese. Results suggest that there are differences in preference rating between US and Chinese subjects and that use of the US-based preference function for the RSUI would bias the measurement of rhinitis symptom outcomes in Chinese subjects.