Relationship between in vivo first-order intestinal absorption rate constant and the membrane permeability clearance

An attempt was made to explore the quantitative relationship between the intestinal absorption data obtained from in vivo studies and in situ perfusion studies. The time course of the fraction remaining to be absorbed of L-glucose, erythritol, and urea in the small intestine following the intrajejunal administration to rats was described by a one-compartment model. Thus derived first-order intestinal absorption rate constants (ka) obtained from the in vivo studies in rats were compared with the membrane permeability clearances (CLa,m) estimated in a single-pass perfusion system. Not only were ka and CLa,m in the same increasing order of L-glucose less than erythritol less than urea, but also the operational luminal volumes given as CLa,m/ka were in agreement with the in vivo luminal volume of jejunum estimated by an inulin dilution method. This result suggests that the in vivo intestinal absorption rate (or ka) can be correlated with the intestinal membrane permeability (or CLa,m) by taking the in vivo luminal volume into account.     

Value of approach to the cervical spine by bilateral anterolateral route

The authors report their experience of anterolateral bilateral approach of cervical spine. They underline the advantages and inconvenience of this route and discuss the indications.     

Cancer risk after evaluation for infertility

To evaluate cancer risk by various causes of infertility, the authors conducted a retrospective cohort study among 2,335 women evaluated for infertility at the Mayo Clinic between 1935 and 1964. Most cancers occurred at expected frequencies, with the exception of cancers of the thyroid (standardized incidence ratio (SIR) = 2.6) and other endocrine glands (SIR = 6.7), although analyses were based on small numbers. Patients with progesterone deficiencies (31 per cent of the study subjects) had a 20 per cent higher cancer risk than did those with other causes of infertility, with excesses deriving primarily from cancers of the lung, cervix, ovary, and thyroid and from melanoma. Breast cancer risk, however, was not elevated in either patients with progesterone deficiencies (SIR = 0.9) or patients with other causes of infertility (SIR = 1.0). Examination of other parameters of infertility, including age at evaluation, type of infertility (primary vs. secondary), and years of attempted conception, showed no elevated risks of breast cancer in any subgroup. These results fail to support previous studies that have linked progesterone deficiencies among infertile women to elevated breast cancer risk. However, the data suggest a possible involvement of a progesterone deficiency in the etiology of other cancers, particularly thyroid cancer and melanoma.     

Orthotopic liver transplantation in children

Between 1-1-1982 and 1-1-1988 52 children with an end-stage liver disease were evaluated to determine whether orthotopic liver transplantation (OLT) would be appropriate. 24 children were accepted as candidates in the long term. Twelve were not accepted as potential recipients. The parents of 3 decided not to accept OLT as treatment for their children. Two children died before a suitable donor liver was available, so that OLT was carried out in 11 children. Two of these children needed a second transplant. In 3 children only a part of a donor liver was transplanted. Shortage of donor livers of small size is partly alleviated by using a part of a larger liver. The underlying diseases of the transplanted children were cryptogenic cirrhosis (1x), biliary atresia with a hepatoportoenterostomy (8x) and cirrhosis following neonatal hepatitis (2x). Ten children with OLT are clinically and physically well. Postoperatively a primary graft dysfunction occurred in one child. He was retransplanted. The median waiting time for a donor liver was 5 months. The timing for OLT has to take this in account. In treating children with end-stage liver disease (partial) OLT should be considered.     

Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.