Life, death and the radical moisture. A study of thematic pattern in medieval medical theory.
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Biomedical subjects
Publications and source records attributed to T S Hall.
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Influenza A and influenza B viruses were adapted to growth at 25 degrees C. When given to volunteer subjects, the viruses were attenuated but remained infective and antigenic. The minimum immunizing dose of an egg-adapted virus appeared to be 10(5.0) EID(50). Cloning by plaque selection at 25 degrees C gave seed cultures of relatively low infectivity titres. These titres were increased when necessary by passage at 33 degrees C. No reversion to virulence was observed.Viruses attenuated in the United Kingdom and the USA were compared in volunteer trials with vaccine strains that had already been used in the USSR for mass immunization. Results were broadly similar. Currently available methods of attenuation and work with temperature-sensitive mutants are reviewed.
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This study was done to determine whether core-cooling could provide extended cardiopulmonary preservation and if reimplantation could be simulated and evaluated in the ex vivo autoperfused working heart-lung model. Twenty calves were divided into four groups and placed on cardiopulmonary bypass and rapidly cooled to 15 degrees C. Control heart and lungs were harvested after administration of cardioplegia through the aortic root and were subsequently resuscitated in the autoperfused working heart-lung circuit (group 1) or were orthotopically allotransplanted (group 2). Preserved heart and lungs were similarly excised but stored in a normal saline solution bath at 4 degrees C for 4 hours and then were resuscitated in the autoperfusion circuit (group 3) or were orthotopically allotransplanted (group 4). All groups received isoproterenol during explantation and reperfusion and were studied for 4 hours. Myocardial function was assessed by sonomicrometric techniques, and pulmonary preservation was evaluated by measurements of extravascular lung water, arterial oxygen tension on 100% inspired oxygen, and pulmonary vascular resistance. Cardiorespiratory function after 4-hour static preservation was similar in all four groups except that the arterial oxygen tension in group 1 was lower compared with group 3. Core-cooling on cardiopulmonary bypass without pulmonary artery flushing results in cold ischemic heart-lung preservation, comparable to other currently used modalities. In addition, reperfusion in the ex vivo autoperfusion circuit provides a simplified model to assess the adequacy of cardiopulmonary preservation techniques.
With methylprednisolone as a chemical inhibitor of leukocytes, extended preservation was conducted with an isolated rabbit lung model. The heart-lung blocks of 39 New Zealand white rabbits were flushed in situ with 100 ml of Euro-Collins' solution, harvested, inflated (70%), and preserved at 4 degrees C. Lungs immediately reperfused with whole blood (control lungs, group 1) were compared with lungs preserved without methylprednisolone for 5, 12, and 24 hours (groups 2 to 4) and those preserved with methylprednisolone for 12 and 24 hours (groups 5 and 6, respectively). Methylprednisolone (30 mg/kg) was administered before harvest and was used as an additive to the flush and in the blood reperfusate. Hypothermia and Euro-Collins' flush alone provided adequate preservation for up to 5 hours; however, lung edema was evident by 12 hours of cold ischemia and became severe by 24 hours. By all measured parameters, the lungs in group 5 (treated with methylprednisolone) demonstrated values equal to or better than control lungs. By 24 hours of preservation the beneficial effects of the steroid treatment were no longer evident. Histologic evaluation revealed mild to moderate injury after 5 hours of cold ischemia; progressive edema and hemorrhage were found after 12 and 24 hours of preservation. This injury was significantly ameliorated by methylprednisolone treatment at 12 hours but not at 24 hours. This study suggests that static preservation for up to 5 hours is possible with hypothermia and a Euro-Collins' flush and that extended preservation to 12 hours is possible with pharmacologic dosages of methylprednisolone.(ABSTRACT TRUNCATED AT 250 WORDS)
A cervical heterotopic cardiac allograft model was used to compare noninvasive techniques with endocardial biopsy diagnosis of rejection. The transplant procedure was performed in eight dogs (12 to 16 kg), with a mean ischemic time of 83 minutes. Beginning on the day of the operation each allograft was evaluated daily by palpation, two-dimensional echocardiography, phosphorous nuclear magnetic resonance spectroscopy, and septal endocardial biopsy. At specific intervals after the operation, antimyosin monoclonal antibody (Fab fragment) with an indium-111 label was administered for subsequent gamma camera imaging. Rejection was clinically evident by 2 to 8 days with a mean of 3.5 days. Endocardial biopsy demonstrated moderate to severe rejection by 2 to 4 days. Two-dimensional echocardiography demonstrated early loss of wall thickening dynamics in all allografts. Although subtle changes were evident early in some transplants, these findings were not consistent. After recovery from hypothermic ischemia, evaluation of high energy phosphate metabolites with phosphorous nuclear magnetic resonance spectroscopy showed a progressive decrease in phosphocreatine during mild to moderate rejection, dropping to 30% to 40% of baseline levels with severe rejection. Antimyosin antibody uptake directly correlated with endocardial biopsy rejection scores (R2 = 0.97). With mild to moderate rejection, mean total counts and corrected counts were 222,704 and 112,648, respectively, and were significantly different (p less than 0.05) from baseline counts (135,537 and 58,530) without rejection. As a preliminary finding in untreated acute rejection, both antimyosin antibody and phosphorous nuclear magnetic spectroscopy detected changes consistent with mild to moderate rejection, which usually preceded echocardiographic evidence for injury.(ABSTRACT TRUNCATED AT 250 WORDS)
To examine the pathogenesis of unmodified heart xenograft and allograft rejection, a sequential morphologic analysis was undertaken. Heterotopic cardiac allografts and xenografts were performed by implanting donor hearts into the abdomen of Lewis rats. Xenograft donors were Golden Syrian hamsters and allograft donors were ACI rats. Both xenografts and allografts were excised and examined by light microscopy at specific postoperative intervals. Allograft rejection was found to be a cell-mediated process, beginning with interstitial infiltrates and perivascular cuffing, which progressed to focal myocyte necroses. Ultimately, complete replacement of the myocardium by mononuclear cells was noted in fully rejected hearts. Xenograft rejection was markedly different. Although xenograft rejection was characterized first by interstitial mononuclear cell infiltrates, unlike allografts there was only minimal progression of cellular rejection. Instead, subsequent rejection was characterized by marked interstitial edema and arteriolar vasculitis and thrombosis, leading to extensive infarcts and hemorrhage in fully rejected hearts. Fibrinoid arteriolar changes and the rapid development of edema in the absence of significant cellular infiltrate suggest that cytotoxic antibodies alter xenograft vascular permeability. These data suggest that humoral immunity is largely responsible for acute concordant xenograft rejection, whereas first-set allograft rejection is mainly a cell-mediated process.
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