Analysis of ET‐A and ET‐B receptors using an isolated perfused rat lung preparation

Aims and Methods: The pulmonary and vascular effects of endothelin‐1 receptor activation were studied in isolated perfused and ventilated lung preparations from rat. The responses to endothelin‐1 (ET‐1) and the endothelin B (ET_B) receptor agonist sarafotoxin 6c (S6c) were characterized using the endothelin A (ET_A)‐receptor antagonist FR 139317, the ET_B‐receptor antagonist BQ 788 and the combined ET_A/ET_B‐receptor antagonist Bosentan. The respiratory parameter airway conductance (G_aw) and the vascular parameter perfusion flow were analysed simultaneously. Results: Concentration–response curves for ET‐1 administered intra‐arterially revealed that its most potent effect was on the vascular side while S6c had a more potent effect on airway conductance. ET‐1, given as a bolus dose intra‐arterially (100 μL of 0.2 nm ), induced a strong‐ and long‐lasting contraction of the vasculature while only a less pronounced contraction was seen in the airways. Neither of the antagonists had a significant effect per se on G_aw or perfusion flow. FR 139317 reduced the effect of ET‐1 on perfusion flow by about 50%, while airway conductance was augmented. BQ 788 enhanced the decrease in perfusion flow by ET‐1 while G_aw was not influenced. The combined ET_A/ET_B antagonist Bosentan powerfully prevented the ET‐1‐induced decrease in G_aw but did not alter its reduction in perfusion flow. Conclusions: The potent effect of ET‐1 on the vascular side of the lung is mediated mainly through ET_A receptors, whereas both ET_A and ET_B receptors are involved in G_aw in the rat lung.     

Methylprednisolone treatment in acute spinal cord injury: the myth challenged through a structured analysis of published literature.

BACKGROUND CONTEXT: Methylprednisolone has evolved during the 1990s, through the results obtained from the National Acute Spinal Cord Injury Studies NASCIS II and III, as a standard treatment in acute spinal injury. PURPOSE: To evaluate the scientific basic for the use of methylprednisolone in acute spinal cord injury. STUDY DESIGN: Systematic review of the accumulated literature. METHODS: Critical evaluation of the data obtained in the NASCIS II and III studies plus other accumulated literature. RESULTS: Analyses have been made on subgroups of the study populations, and the results were based on statistical artefacts. Furthermore, improved functional recovery shown by these studies was not clinically significant. CONCLUSION: There is insufficient evidence to support the use of methylprednisolone as a standard treatment in acute spinal cord injury.     

Acute nonlymphatic leukemia among deck officers on coastal tankers: a report of two cases

Deck officers on coastal tankers may be exposed to high concentrations of cargo vapors during loading and tank-cleaning operations. Two cases of acute nonlymphatic leukemia are described. Both men had worked as chief officers on coastal tankers transporting benzene and other petroleum products.     

Endotoxins in cardiopulmonary bypass

Endotoxins are biologically active substances derived from the cell wall of degraded gram-negative bacteria. Since sterile water may also contain large amounts of endotoxins, these are easily introduced into the manufacturing processes of technical medical material, such as the extracorporeal components used in cardiopulmonary bypass. In hemodialysis, the presence of endotoxins has been related to untoward effects in patients. Using the limulus amebocyte lysate test, we determined the serum concentration of endotoxin in 42 patients undergoing coronary bypass operations. The values increased during cardiopulmonary bypass, exceeding the normal range of 0 to 20 ng/L in 10 patients with a maximum of 82 ng/L, which probably indicates endotoxin release from the extracorporeal equipment. We found no obvious relation to postoperative morbidity. The endotoxin levels of this study are considerably lower than those reported in two other studies of patients having cardiopulmonary bypass. This might be due to less intraoperative contamination but possibly also to differences in analytic methods.     

Cancer survival in Estonian migrants to Sweden.

OBJECTIVE: To quantify the eventual extra loss of life incurred to cancer patients in Estonia compared with those in Sweden that was possibly attributable to differences in society. DESIGN: Population based survival of cancer patients in Estonia was compared with that of Estonian immigrants to Sweden and that of all cancer patients in Sweden. The cancer sites studied were female breast and ovary, male lung and prostate, and male and female stomach and colon. SETTING: Data on incident cases of cancer were obtained from the population based Swedish and Estonian cancer registries. PARTICIPANTS: Data from Estonian patients in Sweden, Estonian patients in Estonia, and patients from the total Swedish population were included in the study. MAIN RESULTS: Differences in survival among the three populations, controlling for follow-up time and age at diagnosis, were observed in breast, colon, lung, ovarian, and prostate cancers. The survival rates of Estonians living in Sweden and the total population of Sweden were better than that of the Estonians living in Estonia. For cancers of the breast and prostate, the excess mortality in the older age group (75 and above) was much greater in Estonia than in the other populations. CONCLUSIONS: Most differences in cancer survival between Estonian and Swedish populations studied could be attributed to a longer delay in diagnosis, and also to inferior treatment (including access to treatment) in Estonia compared with Sweden. Estonia's lag in socioeconomic development, particularly in its public health organisation and funding, is probably the main source of the differences observed.     

Selective cytotoxic activity of cyclosporins against tumor cells from patients with B cell chronic lymphocytic leukemia.

A fluorometric microculture cytotoxicity assay was employed for the study of cyclosporin A induced cytotoxicity in tumor samples from patients with B type chronic lymphocytic leukemia (B-CLL). Tumor cells from patients with B-CLL were found to be significantly more sensitive to the cytotoxic actions of cyclosporin A than normal blood mononuclear cells and tumor cells obtained from patients with different types of acute leukemia and solid tumors. The effect of cyclosporin A on B-CLL samples could be reproduced by a non-immunosuppressive cyclosporin A analogue. One B-CLL patient treated with cyclosporin A responded with a significant decrease in tumor mass and alleviation of anemia and B symptoms. The results show that cyclosporin A and its non-immunosuppressive analogues appear selectively toxic to B-CLL cells, an observation which may have clinical implications.     

Corneal D.C. recordings of slow ocular potential changes such as the ERG c-wave and the light peak in clinical work

A set-up for D.C. recordings of slow ocular potentials such as the c-wave of the electroretinogram (ERG) as well as the fast oscillation (FO), the light peak (LP) and the dark trough (DT) in both clinical and experimental work is described. It includes matched calomel half-cells connected by saline-agar bridges to a corneal contact lens on the eye and a reference chamber on the forehead, a low-drift differential-input D.C. amplifier, an A/D converter, a computer, a thermoprinter, a flexible disc memory, a plotter, and a device for light stimulation controlled by the computer.Examples of the usefulness of the set-up in clinical work are shown in the form of D.C. c-wave ERGs of normal subjects as well as of patients with vitelliform macular degeneration, choriocapillaris atrophy, and retinitis pigmentosa. The direct corneal recording of the FO and LP is demonstrated as well. The different origins of the standing potential (SP) of the eye, the ERG c-wave, the FO and the LP are reviewed briefly.     

A European multicenter study of chronic graft-versus-host disease. The role of cytomegalovirus serology in recipients and donors--acute graft-versus-host disease, and splenectomy

A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed.