Intraocular penetration kinetics of prednisolone after subconjunctival injection in rabbits

Prednisolone concentrations in cornea, aqueous humor, and vitreous humor and the residual amount in conjunctival tissue were assayed by high-performance liquid chromatography during a 14-hour period after subconjunctival injection of prednisolone sodium succinate in rabbits. Prednisolone was concentrated in the corneal epithelium and reached a peak within 5 min, whereas the peak level of prednisolone in stroma-endothelium was achieved 1 h after the injection. There was an apparent linear binding of prednisolone with the ocular tissue homogenates and fluids except for the vitreous humor. However, the protein binding of prednisolone with vitreous humor showed marked concentration dependency. A pharmacokinetic model involving a rapid conversion to prednisolone from its ester prodrug, first-order transfer to various tissues, and first-order elimination of unbound prednisolone from vitreous humor succeeded in predicting the observed concentration-time profiles of prednisolone in various ocular tissues and fluids after subconjunctival injection at three different doses: 0.1, 1.0, and 10.0 mg/kg. The present model predicted that absorption into precorneal area and epithelium and direct penetration into aqueous humor and vitreous humor are 1.7, 0.1, and 0.2% of the applied dose, respectively, and that almost the entire dose (98%) is absorbed into the systemic circulation, with a half-life of 38 min.     

Increasing evidence of the rise of cancer in workers exposed to vinylchloride.

The results of a cancer mortality study among workers employed in the production of vinylchloride and polyvinylchloride between 1939 and 1977 suggest a significant increase in deaths from malignancies of the lymphatic and haemopoietic tissues. Mortality for tumours of the digestive organs, respiratory system, bone and connective tissues, brain, and skin are also greater than in the general population. There were no registered cases of liver angiosarcoma in the study cohort during the follow up period. The risk of cancer was highest among the workers exposed to concentrations of VC of 300 mg/m3 and more who had worked at the plant for 15 to 19 years. The relatively high number of leukaemias and lymphomas in the study group and the absence of liver angiosarcomas probably reflects specific carcinogenic action of different doses of vinylchloride.     

Optimal Selection of Sib Pairs from Random Samples for Linkage Analysis of a QTL Using the EDAC Test

Percentages of extremely concordant and extremely discordant sib pairs are calculated that maximize the power to detect a quantitative trait locus (QTL) under a variety of circumstances using the EDAC test. We assume a large fixed number of randomly sampled sib pairs, such as one would hope to find in the large twin registries, and limited resources to genotype a certain number of selected sib pairs. Our aim is to investigate whether optimal selection can be achieved when prior knowledge concerning the QTL gene action, QTL allele frequency, QTL effect size, and background (residual) sib correlation is limited or absent. To this end we calculate the best selection percentages for a large number of models, which differ in QTL gene action allele frequency, background correlation, and QTL effect size. By averaging these percentages over gene action, over allele frequency, over gene action, and over allele frequencies, we arrive at general recommendations concerning selection percentages. The soundness of these recommendations is subsequently in a number of test cases.     

The use of perfluorinated emulsion for prolongation of the endurance period in lethal hypoxia

The apnea model with venovenous perfusion and blood oxygenation in a membrane oxygenator was used to study the gas transport characteristics of perfluorinated emulsion with the aim to prolong the endurance period in lethal hypoxia. The use of PFOS emulsion (40 ml/kg) as a hemodilution agent at relatively low rate of assisted perfusion (35 ml/kg×min) produced no improvement of oxygen supply during the critical period in comparison with conventional plasma substitutes. However, perfusion with oxygenated perfluorinated emulsion prolonged survival as compared with polyglucin perfusion, mainly due to the maintenance of the vitally important organs (heart and brain) and due to the improvement of microcirculation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 477–480, October, 1997     

Closed versus open mitral commissurotomy in pure noncalcific mitral stenosis: hemodynamic studies before and after operation

Controversy persists regarding whether the efficacy of closed instrumental mitral commissurotomy compares well enough with that of open commissurotomy to warrant its continued use. The purpose of this study was to compare the results of operation as determined by catheterization studies in 63 patients with pure, severe, and noncalcified mitral stenosis. The patients were randomly assigned to one of two groups: thirty-two patients were operated on by the closed technique (group I) and 31 by the open technique (group II). All patients underwent left-sided and right-sided catheterization before and 4 months after operation. Preoperatively the two groups were statistically similar with regard to major clinical data and hemodynamic findings. There were no deaths at operation or systemic embolism in the two groups. The prevalence of surgically induced mitral regurgitation was similar in the two groups (12.4% versus 12.9%). Pulmonary arterial pressure and arteriolar and total pulmonary vascular resistance decreased significantly in the two groups. Pulmonary capillary wedge pressure decreased from 23.3 +/- 8.5 to 15.8 +/- 7 mm Hg in group I (p less than 0.001) and from 23.7 +/- 6 to 14 +/- 5.8 mm Hg in group II (p less than 0.001). Cardiac index increased from 2.86 +/- 0.84 to 3.14 +/- 0.78 L/min/m2 in group I, but this increase did not reach statistical significance. In group II cardiac index increased from 2.89 +/- 0.6 to 3.6 +/- 0.6 L/min/m2 (p less than 0.005). The mean and end-diastolic transmitral pressure gradients decreased significantly in the two groups, but the decrease was statistically greater in the open mitral commissurotomy group (p less than 0.001). Mitral valve area increased from 0.82 +/- 0.18 to 1.4 +/- 0.40 cm2 in group I (p less than 0.01) and from 0.84 +/- 0.15 to 2.14 +/- 0.53 cm2 in group II (p less than 0.001). The mean increase in mitral valve area was 0.61 cm2 in group I and 1.34 cm2 in group II (p less than 0.001). At exercise, in patients with resting pulmonary capillary wedge pressures of 18 mm Hg or less, cardiac index increased by 36% in group I (23 patients) and 48% in group II (24 patients), because of a smaller mitral valve area in group I (1.61 +/- 0.39 cm2) than in group II (2.45 +/- 0.65 cm2). Thus open commissurotomy improved hemodynamic values to a greater extent than closed commissurotomy at both rest and exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Midazolam for rapid sequence induction

We compared midazolam 0.2 mg.kg-1 and fentanyl 50 micrograms with thiamylal 4 mg.kg-1 for rapid sequence induction. We could use midazolam safely in patients with bronchial asthma or drug allergy. There was no difference in time from the beginning of induction to intubation between midazolam treated group and thiamylal treated group. Changes in systolic as well as diastolic blood pressure and heart rate during 2 hours from intubation were smaller in midazolam treated group than in thiamylal treated group. In midazolam treated group, no arrhythmias were observed at the time of intubation. We could reduce the amount of anesthetics in midazolam treated group during 2 hours from intubation. From the results mentioned above, we conclude that midazolam is a useful agent for rapid sequence induction.