A study of the relationship between mass and physical strength of keratin bars in vivo.

A study was undertaken of the changes in the mass and physical properties of keratin bars implanted subcutaneously in adult rats. A very gradual decrease occurred in vivo in the dry weight of the bars over the period of the study (up to 18 weeks). The elastic modulus of the bars decreased abruptly when present in vivo between 3 and 6 weeks. At the same time there was an increase in the number of cavitations and fissures at the surface of the bars, and an increase in a central internal region of the bars where there was a disorganisation in structure of the polymer. A biocompatible material showing such changes in vivo is likely to be suitable for a variety of medical and surgical applications in which it provides a framework for cell invasion.

Osseous regeneration in the presence of oxidized cellulose and collagen.

Oxidized cellulose and collagen are two absorbable hemostatic scaffolding materials that are used widely in surgery. A histomorphological study was undertaken to determine the tissue response and extent of healing brought about by intraosseously implanting these two materials in the femur and tibia of sheep. There was no major difference in the rate of repair of the bone defects brought about by these two materials, with the bone defects being completely repaired by lamellar bone at 6-8 weeks. Therefore, our results suggest that, in most instances where collagen is presently used in surgical applications, it could be substituted by oxidized cellulose.

Regulation of platelet-activating factor (PAF) activity in human diseases by phospholipase A2 inhibitors, PAF acetylhydrolases, PAF receptor antagonists and free radical scavengers.

The aim of this review is to present recent findings indicating the likely involvement of platelet-activating factor (PAF) in human diseases, and possible ways of alleviating its harmful effects. PAF is a potent proinflammatory mediator and promotes adhesive interactions between leukocytes and endothelial cells, leading to transendothelial migration of leukocytes, by a process of juxtacrine intercellular signalling. This process leads to activation of leukocytes and the release of reactive oxygen radicals, lipid mediators, cytokines and enzymes. These reaction products subsequently contribute to the pathological features of various inflammatory diseases. The reactive oxygen radicals cause low density lipoprotein (LDL) oxidation which mediates the development of atherosclerosis. Oxidized LDL may damage cellular and subcellular membranes, leading to tissue injury and cell death. Among the therapeutic approaches considered are agents that inhibit/degrade proinflammatory mediators and thereby have anti-inflammatory and/or anti-atherogenic potential. These include inhibitors of phospholipase A2 activity, PAF-acetylhydrolases, PAF antagonists and free radical scavengers/antioxidants, the latter protecting against oxidized LDL-induced cytotoxicity.

RU486 combined with PGE1 analog in voluntary termination of early pregnancy--a comparison of recent findings with gemeprost or misoprostol.

This paper addresses itself to comparing the findings from more recent studies on the termination of early pregnancy in women by a medical method involving a combination of RU486 and gemeprost (a PGE1 analog which is administered as a vaginal pessary) or RU486 and misoprostol (an orally active PGE1 analog). In particular, the data in these studies relating to (i) time to expulsion of the conceptus and (ii) duration of vaginal bleeding have been compared by statistical tests. It was shown that the shortest time to expulsion after PGE1 was when gemeprost was administered at 48hr following RU486. There was also an increased duration of bleeding with this treatment. These findings are discussed in relation to women's attitudes toward abortion methods especially in regard to preferring a decreased induction-abortion interval and a duration of bleeding of less than 14 days.

Identification of two different rate-limiting mechanisms controlling the release of NSAIDs from silastic polymeric devices, and possible implications.

Two different rate-limiting mechanisms have been found by examining the release characteristics of meclofenamic acid, BW755C.hydrochloride, and diclofenac sodium from silastic polymeric rods into phosphate (0.1 M, pH 7.3) at 37 degrees C. Experiments were performed using rods with initial drug concentrations of 3, 6 and 9% w/w and plots of Q-t and Q-t1/2 were made (Q, cumulative amount of drug released into solution; t, time). For each of the three loadings of meclofenamic acid, the Q-t1/2 plot was linear which indicated a matrix controlled release of the drug. With diclofenac sodium, each of the three loadings gave a Q-t plot that was linear thereby indicating a partition controlled release of this drug. For BW755C.HCl, the release of the drug from rods at the two lowest loadings was matrix controlled, but release from rods at the highest loading was partition controlled. The possible implications of these findings are discussed in regard to medicated vaginal devices or intracervical devices.

Students' written reports as an essential part of a case-based learning programme in anatomy.

This paper reports on second-year medical students' views and performance on the written reports for the cases that were studied in a case-based learning programme in anatomy at the University of Otago in 1988. The mean marks for the reports for the three main categories of student entry are presented. Differential performance on the written reports relative to the case-based component of the examination held at the end of the year has been determined for each student in the class and ranked in order. The proportions of students falling in the top and bottom quartiles for the class are given. The data taken together indicate that with an intensive programme of case-based learning in 1988, optimal performance in the written reports was reached at an early stage by the graduates whereas the two undergraduate categories improved their performance towards the end of the programme.

Prostaglandin E production by uteri of ovariectomized pregnant rats receiving antiprogesterone steroid or in which progesterone has been withdrawn.

Antiprogesterone steroid, ZK98299 (Schering, Germany) or RU38486 (Roussel Uclaf, France), has been administered to ovariectomized early pregnant rats receiving continuous steroid replacement. At 24 h later, uterine explants of rats treated with ZK98299 produced significantly greater amounts of prostaglandin E (PGE) than did controls or animals treated with RU38486. The PGE/PGF2 alpha production ratio for uteri of rats treated with ZK98299 or RU38486 was markedly lowered compared to controls, and a significant decrease occurred in the PGE/6-keto PGF1 alpha production ratio for rats treated with RU38486. For ovariectomized early pregnant rats in which progesterone has been withdrawn, a significant reduction in uterine PGE production occurred when compared to control animals. There was also a marked decrease in PGE/PGF2 alpha production ratio, and the PGE/6-keto PGF1 alpha production ratio tended to be lowered relative to controls. The stimulated production (as by ZK98299) or unchanged production of PGE (as by RU38486) indicates a selective action on uterine PGE synthesis among the antiprogesterone steroids, and these findings cannot be explained simply in terms of a blockage of progesterone receptors.

Uterine production of prostaglandins F2 alpha and 6-keto-F1 alpha by ovariectomized pregnant rats receiving antiprogesterone steroid or in which progesterone has been withdrawn.

Ovariectomized early pregnant rats given continuous steroid replacement therapy have been treated with antiprogesterone steroid, ZK98299 or RU38486. At 24 h following treatment, uterine explants in culture were found to produce significantly greater amounts of PGF2 alpha, but not of 6-keto-PGF1 alpha, when compared to controls. ZK98299 and RU38486 gave almost identical levels of uterine PG production. The 6-keto-PGF1 alpha/PGF2 alpha production ratio for uteri of treated rats was decreased by 45% relative to controls. Similar changes in uterine PGF2 alpha production and 6-keto-PGF1 alpha/PGF2 alpha ratio have been shown for ovariectomized early pregnant rats in which progesterone has been withdrawn when compared to control animals. It has been suggested that inhibiting or withdrawing progesterone in rat uteri exposed to estradiol and progesterone may lead to a stimulation of endoperoxide F-reductase and/or E2 9-ketoreductase activities. The presence of luminal fluid in the uteri was observed for animals treated with antiprogesterone steroid or in which progesterone had been withdrawn. This was associated with a decrease in % dry weight for the uteri of these animals.

Performance of medical students in case-based and essay components of written anatomy examinations.

This paper reports on second-year medical students' performance in the case-based and traditional essay components of the gross anatomy written examinations at the University of Otago held at the end of 1988 and 1989. The mean marks for these two components of the examinations are presented for the three main categories of student entry. Differential performance on the case-based component relative to the essay component has been determined for each student in the class and ranked in order. The proportions of students in the three entry categories falling in the various quartiles for the class are given. The data show that when an intensive programme of case-based learning was followed, as in 1988, all three categories performed similarly on the case-based component relative to the essay component. When a less intensive programme of case-based learning was used, as in 1989, the differential performance of the preferential undergraduate and graduate categories was different to each other. The findings suggest that the achievement of students in the case-based projects is dependent upon the organization of the programme and the extent to which students and staff become involved in the projects. The writing of reports on the cases by students for assessment in 1988 may have had an important influence on the outcome for this year.

Platelet-activating factor (PAF) and its relation to prostaglandins, leukotrienes and other aspects of arachidonate metabolism.

This article summarizes some of the previously reported findings regarding a lipid mediator known as platelet-activating factor (PAF), and briefly describes its effects on cells and tissues. The effects of PAF have also been considered in relation to certain products of arachidonate metabolism released in response to PAF.

Self-directed learning in anatomy: incorporation of case-based studies into a conventional medical curriculum.

This paper reports an attempt to develop self-directed learning skills in second-year medical students by introducing case-based projects into the gross anatomy course at a long-established medical school. The programme and students' responses to a questionnaire completed at the end of the year are presented. Information on the various resources used by students to find information is given. The performance of students in the case-based components of the course has been evaluated and also in the more traditional end-of-year written examination. The data confirm that students have recognized that the projects were about obtaining a deeper understanding of the anatomy, and the programme appears to have promoted the use and study of library texts.

A method of removing gels from narrow-diameter glass tubes as part of a mini-two-dimensional electrophoresis procedure.

A glass chamber that facilitates the removal of polyacrylamide gels from narrow glass tubes after the completion of isoelectric focusing is described. The tube is firmly held at one end of the glass chamber and a syringe is connected to the other end. By slowly forcing water from the syringe into the glass chamber, sufficient pressure can be generated to cause the rod gel to move slowly out of the glass tube. The rod gel is then used for the second stage of a mini-two-dimensional electrophoresis technique. Rod gels of 1.7-mm diameter have been used most extensively and can be removed from the glass tubes with almost 100% success.

Prostaglandin synthesis by isolated cells of rat uterus: production rates, and effects of indomethacin and histamine.

Luminal epithelial and residual cells (mainly of the endometrial stromal tissue) of proestrous rat uteri have been isolated and cultured in defined medium. The prostaglandins produced during a short-term incubation (2 h) in the presence of 10 microM arachidonic acid (to optimize PG production) were determined by direct assay of the culture medium. For the epithelial cells, PGF2 alpha was produced in greatest amounts, followed by 6-keto PGF1 alpha and PGE, while low levels were synthesized by the residual cells. The synthesis of PGF2 alpha by the epithelial cells was inhibited by incorporating indomethacin into the medium and an IC50 value of 2.3 microM was obtained. Incubations performed with histamine in the absence of exogenous arachidonic acid indicated that the pathways for the production of individual prostaglandins were followed to different relative extents, with the production of 6-keto PGF1 alpha being enhanced for both groups of cells when compared to incubations with arachidonic acid.

Prostaglandin production by isolated cells of rat uterus incubated with or without progesterone.

The production of prostaglandins F2 alpha and 6-keto F1 alpha in vitro by the luminal epithelial and the residual (mainly stomal) cells isolated from the uteri of proestrous rats have been measured. The basic procedure involved culturing the cells overnight, washing, and then incubating for 2 h when the amounts of prostaglandins released into the medium were determined by radioimmunoassay. No significant change occurred when the epithelial cells were incubated in the combined presence of arachidonic acid and progesterone for the short-term culture compared to being incubated with arachidonic acid alone. However, when progesterone was incorporated into the medium for the overnight culture, a significant increase occurred in 6-keto PGF1 alpha production by the epithelial cells, without any change in PGF2 alpha, compared to when the cells were incubated overnight in the absence of progesterone. It is suggested that overnight treatment of the epithelial cells with progesterone increases the amount or activity of prostacyclin synthetase, responsible for converting PGH2 endoperoxide to PGI2. Very low levels of prostaglandin production were found for the residual cells.