Treatment strategies of hamster-to-rat cardiac xenotransplantation.
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Animals↗
Biomedical subjects
B Nielsen
Publications and source records attributed to B Nielsen.
An ultrastructural analysis of concordant and discordant cardiac xenografts in unmodified recipients. A sequential study in rodents with special reference to endothelial cell changes in the microvascular system.
Ultrastructural changes in endothelial cells in a hamster-to-rat and guinea pig-to-rat heart transplantation model are described. In the hamster-to-rat model, changes were minimal with an increase in cytoplasmic vesicles 4-6 h after transplantation. 16-24 h after transplantation larger vesicles appeared and the basement and cell membranes were less well defined. 42-48 h after transplantation the changes had progressed with destruction of cell membranes and the appearance of extravasated changes had progressed with destruction of cell membranes and the appearance of extravasated erythrocytes. At the time of complete rejection, changes had further progressed with widespread endothelial cell destruction and infiltration of neutrophilic granulocytes and macrophages, and large amounts of fibrin were present. In the guinea pig-to-rat model, changes were characterized by the appearance of platelets in close contact with the endothelium of the capillaries 1-3 min after transplantation. 4-6 min after transplantation the basement membranes as well as the cell membranes were affected with indistinct borders and interruption. Occasionally fusion of platelets and endothelial cell membranes was demonstrated. In the grafts examined 7-9 min after transplantation, changes had further progressed. Massive aggregation of platelets now appeared in relation to remnants of endothelial cells. Signs of microvascular damage appeared in both models, but with different morphology. In hamster grafts, endothelial cell activation is indicated by gradual changes in the cell membranes resulting in vascular damage and infiltration of the grafts by macrophages and neutrophilic granulocytes. In the guinea pig grafts, activation of endothelial cells results in platelet aggregation, formation of microthrombi, and subsequent tissue damage. Even though antibody and complement are involved in both types of rejection the basic mechanisms are different.
Animals↗
Distribution of point defects in Si(100)/Si grown by low-temperature molecular-beam epitaxy and solid-phase epitaxy.
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Journal Article↗
[Educational requirements of younger psychiatrists].
In order to define the requirements junior medical staff in postgraduate psychiatric training would wish to make for future postgraduate training in adult psychiatry, a questionnaire with 66 questions was sent in June 1990 to postgraduate trainees at all departments of child psychiatry and adult psychiatry in the country. Response was anonymous. The article deals with the responses from 264 persons either intending to undergo specialist training in adult psychiatry or having already completed it. Sixty-four percent stated a need for better individual clinical guidance. The majority stated that eight hours every week should be earmarked for formal tuition and research (two hrs clinical tuition, two hrs theory, two hrs supervision in psychotherapy, and two hrs for research). On average, the trainees had used 4200 DKK of their own income and four free days on courses over the previous year. Twenty-four months was proposed as adequate for an introductory appointment. The majority held that appointments should be made on the basis of the traditional curriculum vitae (82%) and a personal interview (86%), while about 20% believed that written or oral references should also be a requirement. Sixty-nine percent believed that selection of applicants for teaching appointments should be made locally with central supervision. Twenty-six percent felt they had been passed over in appointment situations, and 68% claimed it was due to nepotism. Recommendations for modifications of the future postgraduate training according to the responses are proposed, and it is concluded that earmarked resources are necessary, if the intention in the educational reform now in progress is to be realized.
Adult↗
Erythropoietin and fibrinolysis effects on platelet activity.
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Blood Platelets↗
Anti-CD4 monoclonal antibody treatment combined with total lymphoid irradiation and cyclosporin A in hamster-to-rat cardiac transplantation. Analysis of lymphocyte subsets and anti-donor xenoantibodies.
Combined treatment with total lymphoid irradiation and cyclosporin A results in prolonged graft survival in concordant xenogeneic cardiac transplantation, but reproducible long-term graft acceptance has proved to be difficult. Anti-CD4 monoclonal antibody treatment has been successful in inhibiting heart graft rejection in allogeneic models. Used as monotherapy in a concordant xenogeneic model for pancreatic islet transplantation, prolonged graft survival has been reported; however, no beneficial effect on primarily vascularized heart grafts was noted. The object of this investigation was to combine these treatment strategies with respect to reproducible long-term hamster heart graft survival in rats, to monitor the effect on lymphocyte subpopulations, and to determine possible anti-donor antibody formation correlated to time of rejection. Graft survival after combined preoperative total lymphoid irradiation and postoperative cyclosporin A + anti-CD4 monoclonal antibody treatment was prolonged from 14 to > 100 days (compared to spontaneous graft survival of three to four days), with long-term graft function in four of 19 recipients. Total white blood counts in the postoperative course were characterized by an unproportional increase of Ig+ cells and an incomplete recovery of CD4+ cells. Flow-cytometric analysis of anti-donor antibodies showed low levels of preformed antibodies and increasing amounts of strain-, but not donor-specific antibodies, correlated to the time of rejection. Long-term survivors with functioning grafts at the time of sacrifice had an initially moderate antibody increase with subsequent decrease to baseline levels. Our results indicate that total lymphoid irradiation combined with cyclosporin A and anti-CD4 monoclonal antibodies can prolong graft survival significantly in concordant hamster-to-rat cardiac xenotransplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Expression and regulation of an interferon-alpha-inducible membrane protein p106 on human hematopoietic cells.
p106 is a human membrane protein of 106 kD previously shown to be inducible by interferon-alpha (IFN-alpha) on Daudi cells. To investigate the role of p106 further, its distribution and inducibility within hematopoietic cells was studied. Multiparameter flow cytometry (FCM) analysis showed that p106 expression was restricted to B cells and monocytes, and in both cell lineages acquired at a late stage of differentiation. Thus, p106 was found on mature B lymphocytes and monocytes in peripheral blood and on a variety of freshly isolated leukemic cells of B and myeloid origin as well as on a variety of cultured B-cell lines. In contrast, no expression was found on T lymphocytes, natural killer (NK) cells or granulocytes. p106 expression could be further induced by IFN-alpha on monocytes and Daudi cells, and this capacity was shown to be selective for IFN-alpha, since no other cytokines tested induced p106. Moreover, IFN-alpha therapy of chronic myeloid leukemia (CML) and hairy cell leukemia (HCL) patients lead to a clearcut induction of p106 on such malignant cells. The distribution of p106 could suggest that it represents an activation antigen. Further studies, including cloning of p106 cDNA, are needed to determine the function of p106.
Cytokines↗
Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2.
Fetal antigen 1 was purified from second trimester human amniotic fluid by immunospecific affinity chromatography followed by reversed-phase chromatography. Fetal antigen 1 is a single chain glycoprotein with a M(r) of 32-38 kDa. The amino acid composition revealed a high content of cysteines, prolines and amino acids (aa) with acidic side-chains indicating that fetal antigen 1 is a compactly folded, strongly hydrophilic molecule. The N-terminal amino acid sequence (37 aa) revealed no homology to other known protein sequences, implying that fetal antigen 1 is a 'novel' human protein. When the aa sequence was back-translated into the appropriate degenerate sequence of nucleic acids, fetal antigen 1 could be partially aligned to a 'human adrenal-specific mRNA, pG2'. The indirect immunoperoxidase technique demonstrated fetal antigen 1 in fetal hepatocytes, glandular cells of fetal pancreas and in fetal adrenal cortex, whereas fetal medullary cells were fetal antigen 1 negative. In adult specimens fetal antigen 1 was exclusively found within the beta cells of the islets of Langerhans and in the adrenals with pronounced staining in the cortex. Our observations suggest that fetal antigen 1 is encoded by the mRNA defined by the cDNA clone pG2, but definitive sequencing and expression studies of this mRNA have not been achieved.
Adrenal Glands↗
Impaired thermoregulation in adults with growth hormone deficiency during heat exposure and exercise.
OBJECTIVE: It has recently been shown that patients with growth hormone deficiency have a reduced sweating capacity. We hypothesize that reduced sweating might affect thermoregulation in growth hormone deficiency patients. In the present study we have examined thermoregulation in growth hormone deficiency patients. DESIGN AND PATIENTS: Six adult growth hormone deficiency patients and six matched controls were exposed to a 90-minute heat period (40 degrees C). On a second day the subjects exercised for 30 minutes under standardized conditions. MEASUREMENTS: On both occasions changes in GH secretion, sweating and temperature were registered. Heat storage and evaporation were calculated from these data. RESULTS: We found that during the moderate heat exposure, evaporation was less (56.7 vs 115.6 W, P = 0.0037) and heat storage greater (60.7 vs 37.0 W, P = 0.025) in growth hormone deficiency patients compared to their matched controls. Two of the six patients reacted with severe clinical symptoms of heat exhaustion, whereas the controls were unaffected. After exercise the patients reached significantly higher core temperatures than their matched controls (38.1 vs 37.8 degrees C, P = 0.0097). CONCLUSIONS: Thus, our findings are indicative of a reduced thermoregulatory function in some patients with GH deficiency.
Adult↗
Mononuclear cells from peripheral blood of untreated hairy-cell leukaemia patients enhance the growth of BFU-e.
To further characterise the regulation of haematopoiesis in hairy-cell leukaemia (HCL), we investigated the effect of mononuclear cells from peripheral blood (PBMNC) of untreated HCL patients on the in vitro growth of BFU-e. The effect was tested in an autologous system employing post-treatment HCL PBMNC, and in an allogeneic system. A significant enhancing effect of the pre-treatment HCL PBMNC was seen. In contrast to studies by others, IFN-alpha consistently inhibited the growth of BFU-e from normal donors, from pre- and post-treatment HCL PBMNC, and mixtures thereof. Since PBMNC from patients with very high percentages of circulating hairy cells (HC) also had an enhancing effect, HC was a likely source of one or more enhancing factors. Thus, even though we cannot exclude a minor inhibitory activity of the HC by our assay, their net effect seems to be enhancing, and therefore it seems unlikely that the HC is directly responsible for the anaemia in HCL.
Adult↗
Evidence for a primarily humoral rejection mechanism in concordant xenogeneic heart transplantation. A sequential immunohistological study in a hamster-to-rat model.
Heterotopic heart transplantations in an unmodified hamster-to-rat model were studied sequentially by immunohistochemical analysis. Monoclonal mouse anti-rat antibodies against B cells, T cells, macrophages and neutrophilic granulocytes (MRC OX-19, MRC OX-38, MRC OX-8, MRC OX-22, MRC OX-33, MRC OX-41 and MRC OX-42) were used in an indirect immunoperoxidase technique and monoclonal mouse anti-rat IgM and IgG were used for immunofluorescence. In grafts investigated after 6 h (N = 8) minimal infiltration of macrophages was demonstrated with MRC OX-41+ and MRC OX-42+ cells. No T- or B cells were seen. In a few cases, deposition of IgG and IgM was seen related to the endothelium of larger vessels. In grafts examined 24 h after transplantation (N = 10) the number of MRC OX-41+ and MRC OX-42+ cells had increased and in half of the cases IgM and IgG were located in relation to endothelial cells of larger vessels. In grafts investigated 48 h after transplantation (N = 8) the infiltration with MRC OX-41+ and MRC OX-42+ cells had further increased and a few scattered MRC OX-19+ and MRC OX-8+ cells appeared. At this time all but one heart had deposition of IgG and IgM in the vessel walls. Upon complete rejection (N = 8) diffuse infiltration of MRC OX-41+ and MRC OX-42+ cells was seen, but still only a few scattered T cells could be demonstrated. At this time IgG an IgM deposition appeared in all vessels and was also located in relation to the capillaries. These results further support our hypothesis that acute xenograft rejection in this animal model is primarily of the humoral type.
Animals↗
Human circulatory and thermoregulatory adaptations with heat acclimation and exercise in a hot, dry environment.
1. Heat acclimation was induced in eight subjects by asking them to exercise until exhaustion at 60% of maximum oxygen consumption rate (VO2) for 9-12 consecutive days at an ambient temperature of 40 degrees C, with 10% relative humidity (RH). Five control subjects exercised similarly in a cool environment, 20 degrees C, for 90 min for 9-12 days; of these, three were exposed to exercise at 40 degrees C on the first and last day. 2. Acclimation had occurred as seen by the increased average endurance from 48 min to 80 min, the lower rate of rise in the heart rate (HR) and core temperature and the increased sweating. 3. Cardiac output increased significantly from the first to the final heat exposure from 19.6 to 21.4 l min-1; this was possibly due to an increased plasma volume and stroke volume. 4. The mechanism for the increased plasma volume may be an isosmotic volume expansion caused by influx of protein to the vascular compartment, and a sodium retention induced by a significant increase in aldosterone. 5. The exhaustion coincided with, or was elicited when, core temperature reached 39.7 +/- 0.15 degrees C; with progressing acclimation processes it took progressively longer to reach this level. However, at this point we found no reduction in cardiac output, muscle (leg) blood flow, no changes in substrate utilization or availability, and no recognized accumulated 'fatigue' substances. 6. It is concluded that the high core temperature per se, and not circulatory failure, is the critical factor for the exhaustion during exercise in heat stress.
Acclimatization↗
The hemodynamic and prognostic significance of echo-Doppler-proven mitral regurgitation in patients with dilated cardiomyopathy.
Data from cardiac catheterization at rest and during exercise in 57 patients with dilated cardiomyopathy (DCM) were analyzed to evaluate the bearing of mitral regurgitation (MR) detected by color Doppler echocardiography (CDE) on prognostically important invasive hemodynamic parameters and survival. The etiology of DCM was coronary artery disease in 21 patients and unproven ('idiopathic') in 36 patients. MR was detected by CDE in 34 patients (60%) with an agreement of 93% compared to left ventriculography. Mean age, etiology of DCM and duration of symptoms were similar in patients with and without MR, while patients with MR were in a higher NYHA class, had lower ejection fraction (LVEF) (25 +/- 13 vs. 35 +/- 17%; p < 0.02), larger left ventricular volumes (356 +/- 138 vs. 268 +/- 61 ml; p < 0.01) and higher left ventricular end-diastolic pressure (LVEDP) (21 +/- 9 vs. 13 +/- 7 mm Hg; p < 0.01). At rest, right-sided pressures were higher in patients with MR compared to patients without MR (pulmonary wedge pressure 20 +/- 9 vs. 10 +/- 3 mm Hg, mean pulmonary arterial pressure 30 +/- 11 vs. 20 +/- 8 mm Hg, mean right atrial pressure 9 +/- 4 vs. 4 +/- 2 mm Hg, all p < 0.001), but no significant differences were found in cardiac index (CI) or stroke index (SI).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Nasal reaction to changes in whole body temperature.
The changes in nasal patency following a 1.5 degrees C decrease or increase in whole body temperature were measured in 8 healthy young males, during and after 30 min of immersion in a 15 degrees C cold or a 40 degrees C warm bath, breathing air at the same temperature, in a cross-over experimental design. The nasal reactions were traced by consecutive measurements of changes in nasal cavity volumes by acoustic rhinometry. Swelling of the mucosa during cooling and an almost maximal shrinkage of the mucosa during heating were indicated by respectively a decrease and an increase in nasal cavity volumes. The reactions were determined predominantly by the whole body thermal balance, but were also influenced by the temperature of the inhaled air, either enhanced, reduced or temporarily reversed. The greatest change occurred in the nasal cavity, left or right, which differed most from the final state at the beginning of exposure due to the actual state of nasal cycle.
Adult↗
Nursing audit: measuring the quality of nursing care.
The quality assurance initiative was taken in 1984 in Papua New Guinea as a result of numerous public criticisms of the services and the care given and/or observed by patients and the community. The approach to quality assurance chosen for this nursing audit is a problem-oriented and patient-focused structure, process and outcome method based on World Health Organization principles and adapted from the Dynamic Standard Setting System.
Humans↗
Pain with mammography: fact or fiction?
This article presents an overview of current knowledge about mammography-related pain and discomfort. Possible causes of pain and discomfort are discussed along with the results of two pilot studies that investigated the prevalence and severity of pain and discomfort associated with film-screen mammograms in a mobile screening program. Based on these studies, the authors conclude that pain is a problem for a significant number of women from diverse ethnic and socioeconomic backgrounds. A nursing care plan is provided to assist nurses in reducing mammography-related pain and discomfort.
Female↗
Lifetime of reusable syringes and needles. A field study.
For planning of supplies and costs it is important for an immunization unit to know how many times reusable syringes and needles can be used. A field study found that BCG syringes, which had their rubber seals replaced once, could be used at least 150 times, and DPT syringes more than 200 times even when sterilized in tap water with a hardness of 88 mg calciumoxyde per liter. Needles could be used 100 times and when resharpened several times even more.
Calcium↗