Kinetics of drug action in disease states. XXIX. Effect of experimental nephrotic syndrome on the pharmacodynamics of heptabarbital: implications of severe hypoalbuminemia

The purpose of this investigation was to determine the effect of nephrotic syndrome (NS) on the pharmacodynamics of a barbiturate. NS was induced in male rats by puromycin aminonucleoside; it caused hypoproteinemia, increased liver and kidney weight and elevated serum creatinine and urea nitrogen concentrations. Serum albumin concentration decreased from 3.5% in controls to 0.90% in NS animals. The rats were infused i.v. with heptabarbital, 1 mg/min, until they lost their righting reflex. The total dose (mean +/- S.D.) required by rats with NS, 40.2 +/- 4.2 mg/kg, was substantially lower than that required by normal animals (68.6 +/- 6.2 mg/kg, P less than .001). Serum protein binding of heptabarbital was reduced from 49% in controls to 26% in NS rats. However, the drug concentration in cerebrospinal fluid (CSF) at the pharmacologic endpoint was not significantly different in controls and NS rats (18.9 +/- 1.5 vs. 18.3 +/- 1.4 mg/l). Serum, CSF and the brain contained appreciable concentrations of a metabolite of heptabarbital. To determine if the metabolite contributes to the pharmacologic effect of the parent drug, rats received an i.v. injection of 46, 60 or 100 mg/kg of heptabarbital. Concentrations of heptabarbital in CSF at return of righting reflex (which occurred after 15, 25 and 50 min, respectively) were independent of dose whereas metabolite concentrations increased with increasing dose. Thus, the metabolite of heptabarbital in male rats is pharmacologically inactive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interalar width as a guide in denture tooth selection

This study was undertaken to determine the relationship of the IAW, measured between at the widest dimension of the alae of the nose, and two other measurements of maxillary anterior teeth. The other measurements, both of which are significant in the selection and arrangement of artificial teeth used in complete dentures, were the ICTW and the ARCD measured from the distal surface of the maxillary canine on one side of the arch to the distal surface of the canine on the opposite side of the arch. No distinction was made between either the sex or the age of the subjects. The mean ICTW of 35.35 mm was 3% greater than the mean IAW of 34.28 mm. The mean ARCD of 44.85 mm was 31% greater than the mean IAW of 34.28 mm. This mean ARCD compares favorably (less than 1 mm difference) with a constructed ARCD of 45.8 mm from a tooth dimension study by Shillingburg et al. The ARCD was 44.85 mm. This measurement had not been made in the previous study examining the relationship of interalar distance to ICTW. When the IAW was plotted against the intercanine cusp tip width, a fairly strong correlation coefficient of 0.413 was exhibited. A weaker but definite correlation coefficient of 0.217 was observed when the interalar width plotted against the circumferential arc distance from distal surface to distal surface of the maxillary canines.     

Comparison of Asymmetry in Cerebral Blood Flow Between Brain Hemispheres Using Digital Subtraction Angiography

BACKGROUND AND PURPOSE: Recently, endovascular techniques have gained significant therapeutic potential for both treatment and prevention of stroke. Cerebral angiography, which is an essential component of these procedures, has been used to provide morphological information regarding condition of blood vessels. In this study, we propose to determine the possibility of acquiring information regarding cerebral blood flow (CBF) in addition to morphologic information from data routinely available during angiography. METHODS: Digital subtraction angiography sequences were obtained for eight patients having occlusive disease in internal carotid artery (ICA) territories. Two regions-of-interest (ROIs) corresponding to the two brain hemispheres on AP view were delineated. For each image, the average pixel value within each ROI was calculated and used to generate time-density curves. Indices obtained from each curve were compared with each other and with the results obtained from the single photon emission computed tomography (SPECT) studies performed a pre- or postangiography procedure. RESULTS: Comparison between ICA stenosis and cerebral perfusion measurements revealed that cerebral perfusion deficit can be independent of arterial occlusive disease. The indices obtained from the time-density curves exhibit a correlating trend with the results from SPECT studies. However, lack of sufficient sample data prevented any meaningful statistical analysis to be conducted. CONCLUSIONS: We have developed a technique for utilizing the angiographic data for the important task of routinely and easily measuring CBF. Availability of CBF measurements during cerebral angiography may favorably impact upon the appropriate use of endovascular procedures and potentially contribute to the reduction of morbidity and mortality associated with stroke.     

Effect of ethanol on cyclic AMP levels in intact PC12 cells

Two subclones of the rat pheochromocytoma cell line, PC12, were used to compare the effects of ethanol on adenylate cyclase activity in isolated membranes with its effects on cyclic AMP accumulation in intact cells. Consistent with previous reports, ethanol increased basal and 2-chloroadenosine-stimulated adenylate cyclase activity in isolated membrane preparations from both subclones. However, ethanol had opposite effects on agonist-stimulated cyclic AMP accumulation in intact cells of the two subclones, enhancing accumulation in one subclone, and inhibiting it in the other. The inhibition of cyclic AMP accumulation did not result from stimulation of phosphodiesterase activity, activation of the inhibitory guanyl nucleotide regulatory protein, Gi, or stimulation of protein kinase C. The results indicate that extrapolation of the effects of ethanol from one cell type to another, or from in vitro to in vivo systems, may be complicated by the interaction of ethanol with regulatory processes that influence second messenger systems, and can differ in various types of intact cells.     

Further consideration of the clonal nature of Salmonella typhi: evaluation of molecular and clinical characteristics of strains from Indonesia and Peru.

We examined envelope protein profiles, chromosomal restriction endonuclease digest patterns, and immune responses to envelope proteins for collections of Salmonella typhi strains isolated in Peru and Indonesia. Only minor differences in envelope protein patterns were apparent among strains. Strains from 7 of 20 Indonesian patients had a distinct chromosomal digest pattern compared with patterns of Peruvian and other Indonesian strains. Strains with this pattern carried the gene for the j flagellar antigen (H1-j); differences in response to envelope proteins of j and d strains were noted on immunoblot analysis. Our data suggest that there are genotypic and phenotypic differences among S. typhi strains. The clinical importance of these differences remains to be fully evaluated; however, in this study it was not possible to show a clear correlation between strain characteristics and disease severity.     

In vitro histoculture of human tumors with fluorescent dye end-points measured by confocal microscopy: high correlation of in vitro and in vivo chemosensitivity.

Tumors from 40 patients and 7 established human xenograft tumor lines were grown in three-dimensional histoculture. A Viable-Cell-Index (VCI) based on fluorescent dyes and Growth Fraction Index (GFI) based on [3H]thymidine incorporation were measured by confocal microscopy and histological autoradiography, respectively, after treatment with cytotoxic agents. Chemosensitivity in vitro with the two methods was correlated with chemosensitivity of the same set of human xenografted tumor lines grown in nude mice. The percent accuracy of in vitro to in vivo correlation with VCI (73%) was higher than GFI (63%). The number of false positives with VCI was 12.1% (4/33), and with GFI was 31.3% (10/32). The results thus indicated that in vitro histoculture with fluorescent vital-dye end-points to measure cell viability is of potential use to determine tumor chemosensitivity.