The effect of halothane on the recirculatory pharmacokinetics of physiologic markers

BACKGROUND: The cardiovascular effects of halothane are well recognized, but little is known of how this affects drug distribution. The effect of halothane anesthesia on physiologic factors that affect drug disposition from the moment of injection was investigated. METHODS: The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1%, 1.5%, and 2% halothane in a randomized order determined by a repeated measures Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on frequent early and less frequent later arterial blood samples. These models characterize the role of cardiac output and its distribution on drug disposition. RESULTS: Halothane caused a significant and dose-dependent decrease in cardiac output. The disposition of antipyrine was most profoundly affected by halothane anesthesia, which increased both nondistributive intercompartmental clearance and volume while decreasing fast and slow tissue clearances and elimination clearance in a halothane dose-dependent manner. CONCLUSIONS: Halothane-induced changes in blood flow to the compartments of the antipyrine recirculatory model were not proportional to changes in cardiac output. Halothane anesthesia significantly increased (to more than double) the area under the drug concentration versus time curve due to an increase in the apparent peripheral blood flow not involved in drug distribution, despite a dose-dependent cardiac output decrease. Recirculatory pharmacokinetic models include the best aspects of traditional compartmental and physiologic pharmacokinetic models while offering advantages over both.     

Sequences of the primate epsilon-globin gene: implications for systematics of the marmosets and other New World primates

Sequences of the epsilon-globin gene were determined for five species of marmosets, along with approximately 2 kb of 5' flanking sequence. An analysis of these data, compared with those of other primates strongly supports the classification of Callithrix jacchus and C. geoffroyi into the jacchus group, and C. argentata and C. mauesi into the argentata group. The pygmy marmoset, formerly identified as Cebuella pygmaea joined strongly to the argentata group, indicating that without the pygmy marmoset the genus Callithrix would be paraphyletic. Our data support recent studies which indicate that C. pygmaea should be included in the genus Callithrix. Relationships among other primates were as indicated by previous studies of epsilon-globin sequences. Divergence times were estimated according to a local molecular clock. These calculations indicated the divergence of C. mauesi and C. argentata to be approximately 1.6-1.9 Myr (million years ago), and the most recent common ancestor of the marmosets to be between 4.5 and 4.7 Myr. The latter estimate corresponds well to the date of 4.6 Myr calculated from an independent data set.     

Perinatal asphyxia and heart problems

New bisantrene analogues were synthesized, bearing one or two 4,5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1,4 or 9 of the anthracene ring system. A 10-azabioisostere was also prepared. The position of substituents in structurally isomeric drugs modulates topoisomerase II poisoning and specificity, along with cytotoxicity.     

Regional cerebral metabolism in female alcoholics of moderate severity does not differ from that of controls

It is generally believed that women are more vulnerable to alcohol's toxic effects than men. Studies in male alcoholics have consistently shown reductions in brain glucose metabolism. However, such studies have not been done in female alcoholics. The purpose of this study was to evaluate if similar or worse brain metabolic abnormalities occurred in female alcoholics. For this purpose, we measured regional brain metabolism with positron emission tomography and [18F]fluorodeoxyglucose in 10 recently detoxified female alcoholics and compared it with that in 12 age-matched female controls. There were no differences between alcoholics and control females in regional brain glucose metabolism whether we used regions of interest analysis or statistical parameter maps methods. These results do not support a higher toxicity for the effects of alcohol in the female brain, as assessed with regional brain glucose metabolism, because metabolic values in female alcoholics did not differ from those of controls, whereas metabolic values in male alcoholics are generally lower than those in controls. However, this study is confounded by the fact that the severity of alcohol use in these female alcoholics was less than that of the male alcoholics previously investigated in positron emission tomography studies. Future studies in male subjects with alcoholism of moderate severity are required to address gender differences in sensitivity to alcohol effects in brain metabolism.     

Clinical experience in Hurthle cell tumors

In the period 1987-1997 6 patients with Hürthle cell carcinomas and 4 patients with Hürthle cell adenomas underwent primary surgical treatment (8.1% of all thyroid carcinomas). The diagnosis of Hürthle cell tumor was based on the presence of more then 75% Hürthle cells and the malignity on capsular or/and vascular invasion. All the patients with Hürthle cell cancer underwent total thyroidectomy, in three cases with Hürthle cell adenoma thyroid lobectomy was performed and in one case total thyroidectomy. Follow-up time ranged from 1 to 8 years after surgery (mean 4.5 years). There was no death and no recurrence. The Authors have studied the nuclear DNA content in Hürthle cell tumors: 3 adenomas were euploid and 1 was aneuploid, 4 carcinomas were aneuploid and 2 were euploid. The results in Authors' study of the DNA content and nuclear DNA ploidy are not uniformly consistent enough to allow a distinction between benign and malignant neoplasms and to evaluate the prognosis, but the number of patients and the follow up are still too limited.     

Morphometric and immunocytochemical study of the fetal, infant, and adult human vas deferens

The human vas deferens (VD) is often considered simply as a conduit to transfer mature sperm from the epididymis to the ejaculatory duct. The cells that make up the epithelium of the VD, however, exhibit many characteristics of cells found in more complex epithelia, which are involved in absorption and/or secretion. In the present investigation, morphometry was utilized to characterize in detail the changes incurred by the human VD during its development, growth, and aging and to determine if these changes correlate with testicular maturation. In addition, the specific types of keratins present in the epithelial cells were defined, as well as desmin distribution in the muscular layers, during the various phases of the development, growth, and involution of the human VD. Results of the morphometric study are consistent with the interpretation that the development, growth, and aging of the VD are delayed, but parallel to, the identical phases exhibited by the human testis. Further, a differential expression of distinct keratin types was observed in the VD during the various phases examined in this study. Taken together, these two correlations may suggest that the VD is unlikely to function solely as a conduit for sperm. The rationale for this interpretation is as follows: 1) the complex developmental and maturational changes measured in the present investigation in the human VD are common to other absorptive and/or secretory epithelia; and 2) these changes parallel developmental changes observed in other androgen-dependent epithelia of the male reproductive tract, which also function to contribute components to seminal fluid as well as to provide a conduit for sperm.