Na+/H+ exchange inhibition and antioxidants lack additive protective effects after reperfusion injury in the working heterotopic rat heart isograft.

BACKGROUND: The utility of combining strategies of myocardial protection was studied in intact rat hearts subjected to 1 hour of ischemia and 40 minutes blood reperfusion. METHODS: Lewis rats (n = 48) were divided into 4 transplant groups. Twenty-four hearts were arrested by coronary perfusion with hypothermic Celsior solution at 60 mm Hg. The aortic valve was punctured to introduce volume into the left ventricle (LV), and the hearts were abdominally isografted. Animals were either given both the antioxidant probucol (300 mg/kg) and the sodium-hydrogen exchange inhibitor cariporide (5 mg/kg) (CP; n = 6), just cariporide (CAR; n = 6), just probucol (PROB; n = 6), or neither drug (CON; n = 6). After 40 minutes of blood reperfusion, transplanted hearts were rearrested. The control recipients' native hearts (native; n = 6) were also arrested. Postmortem LV compliance relations and myocardial water content (MWC) were measured. RESULTS: Grafts protected by probucol were significantly more compliant than controls and significantly less compliant than grafts protected by cariporide alone and with both cariporide and probucol (p = 0.0001, analysis of variance). Compliance relations for CP overlapped those for CAR. All grafts were less compliant than natives. MWC was significantly greater in controls and PROB than in natives. CONCLUSIONS: Pretreatment with cariporide in the setting of ischemia-reperfusion injury provides greater protection against the development of diastolic abnormalities than probucol when Celsior solution is used for both arrest and preservation. In this model, there is no advantage to combining the drugs, supporting the hypothesis that there is an overlapping mechanism of protection.     

A novel 37-Kd adhesive membrane protein from cloned murine bone marrow stromal cells and cloned murine hematopoietic progenitor cells

The adhesion of hematopoietic progenitor cells to bone marrow stromal cells is critical to hematopoiesis and involves multiple effector molecules. Stromal cell molecules that participate in this interaction were sought by analyzing the detergent-soluble membrane proteins of GBI/6 stromal cells that could be adsorbed by intact FDCP-1 progenitor cells. A single-chain protein from GBI/6 cells having an apparent molecular weight of 37 Kd was selectively adsorbed by FDCP-1 cells. This protein, designated p37, could be surface-radiolabeled and thus appeared to be exposed on the cell membrane. An apparently identical 37- Kd protein was expressed by three stromal cell lines, by Swiss 3T3 fibroblastic cells, and by FDCP-1 and FDCP-2 progenitor cells. p37 was selectively adsorbed from membrane lysates by a variety of murine hematopoietic cells, including erythrocytes, but not by human erythrocytes. Binding of p37 to cells was calcium-dependent, and was not affected by inhibitors of the hematopoietic homing receptor or the cell-binding or heparin-binding functions of fibronectin. It is proposed that p37 may be a novel adhesive molecule expressed on the surface of a variety of hematopoietic cells that could participate in both homotypic and heterotypic interactions of stromal and progenitor cells.     

Participatory management at Boston's Beth Israel Hospital.

In the mid-1980s, the senior management of Boston's Beth Israel Hospital became concerned that continuous cost-cutting efforts could lower the quality of the hospital's services and the morale of its staff. This led them to investigate organizational approaches to "participatory management" to determine whether any of these might be of value to the hospital. They decided that an approach developed in the 1930s called the "Scanlon Plan" would be compatible with the workplace culture of Beth Israel, could help the hospital meet the ongoing problems of change, and could help the staff at all levels develop a sense that they owned the problems of quality, productivity, and efficiency, which would motivate them to address these problems constructively in the face of necessary budget constraints. This plan has two mechanisms to foster employees' positive participation: (1) a process to ensure that all members of the organization have the opportunity to improve productivity, primarily through an open suggestion system and a responsive committee structure, and (2) a means of providing equitable rewards for all members of the organization as productivity and quality improve. This essay describes in some detail the plan and why it was selected, explains how it was adapted, prepared for, and finally implemented in 1989, and reports its success, lessons learned, and future plans as of early 1992. The authors believe Beth Israel's experience with the Scanlon Plan is noteworthy as an example of a leading teaching hospital's taking a quality improvement program seriously and making it work.     

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.      

The right to an heir in the era of assisted reproduction

The latest remarkable technological advances in assisted reproduction, which enable cryopreservation of spermatozoa, embryos and ovarian tissue, raise difficult and debatable legal, social, ethical and moral issues concerning the right to posthumous reproduction. Furthermore, reports on the attitudes of the general public and of centres licensed for infertility treatment in the United Kingdom found that the majority of women and centres support the idea of posthumous reproduction. In this paper we review the data published on this issue, and after considering the various aspects, we conclude that each case should be discussed and authorized by a multidisciplinary committee that includes physicians, clergy, psychiatrists, psychologists, sociologists and other appropriate parties. In our opinion, the main principles that should guide this committee would allow posthumous reproduction in the context of marriage when a prior consent exists. For unmarried persons, post-mortem donation of gametes should be done only anonymously, if they are in agreement with existing laws concerning infertility treatments in every country and after appropriate consent and proper counselling. Moreover, any case which involves consanguinity or a possibility of incest should be forbidden, both for ethical and genetic reasons. In a case of pre-existing siblings, they should be consulted and their informed consent should be granted in advance so as to avoid legal problems in the inheritance of property.      

Blood supply of the olfactory nerve

Summary The authors report the results of a series of dissections and anatomic sections of the fronto-basal region of the brain and of the anterior cranial fossa in human cadavers. The constant presence of an arachnoidal cistern above the olfactory nerve was verified. The arachnoid separates from the pial membrane and forms a bridge with the ventral part of the olfactory bulb and tract, from the lateral edge of the olfactory sulcus to the medial edge of the gyrus rectus. The cistern is wide in its anterior portion, between the gyrus rectus and the olfactory bulb, and is reduced to a virtual slit in its posterior portion where the tract is lodged in the olfactory sulcus. The olfactory nerve can be separated without damaging fronto-basal arachnoidial adhesions over several centimeters. Dissection of this region after intravascular injection of colored media shows the constant presence of an artery destined to the olfactory bulb and tract. It originates either from the lateral surface of the anterior cerebral a. (segment A2), or from the medial fronto-basal a., and consistently provides terminal branches in front of the olfactory trigone in the medial olfactory sulcus. At their ventral extremity, the olfactory structures are therefore vascularised independently for several centimeters, from the lower face of the frontal lobe. The independent vascularisation of the olfactory nerve, the tenuous and easily detachable adhesions, and the actual presence of a true arachnoidal cistern all contribute to enabling surgical techniques which conserve olfactory function during anterior approaches.

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Vascularisation du nerf olfactif. Rapports méningés et applications chirurgicales

Résumé Les auteurs rapportent les résultats d'une série de dissections et de coupes de la région fronto-basale de l'encéphale et de la fosse crânienne antérieure sur sujets cadavériques. La présence constante d'une citerne arachnoïdienne au dessus du n. olfactif a été vérifiée. L'arachnoïde se sépare du feuillet pial et passe en pont à la partie ventrale du bulbe et du tractus olfactifs, du bord latéral du sillon olfactif au bord médial du gyrus rectus. La citerne est large dans sa portion antérieure, entre le gyrus rectus et le bulbe olfactif, se réduit à une fente virtuelle postérieure lorsque le tractus se loge dans le sillon olfactif. Le n. olfactif peut être séparé sans dommage des adhérences arachnoïdiennes fronto-basales sur quelques centimètres. La dissection de cette région, après injection intravasculaire de masses colorées montre, de façon originale, la présence constante d'une artère destinée au tractus et au bulbe olfactifs. Elle naît soit de la face latérale de l'a. cérébrale antérieure (segment A2), soit de l'a. fronto-basale médiale, pour donner ses branches terminales toujours en avant du trigone olfactif dans le sillon orbitaire médial. Sur quelques centimètres à leur extrémité ventrale, les structures olfactives ont donc une vascularisation indépendante de la face inférieure du lobe frontal. L'indépendance vasculaire du n. olfactif, des adhérences ténues, facilement détachables, et la réalité vérifiée d'une véritable citerne arachnoïdienne permettent d'imaginer des techniques conservatrices de la fonction olfactive utilisées dans plusieurs indications de la chirurgie de la fosse crânienne antérieure.