A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.     

Eye-tracking dysfunction in the affective psychoses and schizophrenia.

Smooth pursuit eye movements to a sinusoidally moving target were recorded using the electro-oculogram in 49 subjects with bipolar disorder, 19 with major depressive disorder and 61 with definite schizophrenia, and compared with 145 normal controls. The signals were analysed in the frequency domain to yield a signal to noise ratio that is known to relate to accuracy of smooth pursuit. Smooth pursuit was found to be significantly poorer in schizophrenics than in bipolars, major depressed or controls. Eye-tracking performance was independent of the effects of neuroleptics, tricyclic antidepressants or lithium, and was not altered by the severity of depression in the affective psychoses. There was a small, but significant worsening of smooth pursuit with age in controls and schizophrenics, but this did not account for the group differences. The results support the view that among the major psychoses eye-tracking dysfunction is specific to schizophrenia.     

Current clinical laboratory practice: investigation of plasma lipids--which tests and when?

Clinical interest in the lipoproteins stems mainly from the association between serum cholesterol concentrations and coronary heart disease. Investigations of lipoproteins should be performed in patients with premature coronary heart disease, with a strong family history of coronary heart disease, or with certain cutaneous stigmata of hyperlipoproteinaemia and when fasting serum samples are seen to be lipaemic. Family studies should be performed in appropriate cases to identify relatives at increased risk of developing coronary heart disease. Patients with conditions known to cause secondary hyperlipoproteinaemia should be investigated if they fall into one of these categories but only after treatment of the underlying condition. Non-specialist laboratories should be able to measure total cholesterol and triglyceride concentrations and high density lipoprotein cholesterol concentrations. Lipoprotein electrophoresis has a limited role in such laboratories and is not necessary as a routine procedure. Specialist laboratories should in addition be able to measure individual lipoproteins and identify apolipoprotein E phenotypes.     

An alternative approach to contrast-detail testing of X-ray image intensifier systems.

The difficulties of making the results of threshold contrast-detail diameter tests on X-ray image intensifier systems consistent with published performance standards are discussed. The current approach to contrast-detail testing is described and an alternative method intended to give greater consistency for all image intensifier input field diameters proposed. The current and alternative test conditions are compared on two image intensifier systems. The results obtained show that the contrast-detail curves for image intensifier systems with a wide range of input field diameters can be effectively normalized to be directly comparable to a common reference standard by applying the proposed alternative test conditions. The implications of this result on the interpretation of the contrast-detail test are discussed.     

Space time clustering of births in SIDS: do perinatal infections play a role?

The aetiology of sudden infant death syndrome (SIDS) remains uncertain; many causal pathways have been proposed. In this paper we have examined firstly the variation in the risk of SIDS with age, month of death and month of birth; and secondly the space time clustering of SIDS deaths, and, separately, space time clustering of their births. Data were obtained from the Office of Populations, Censuses and Surveys on all certified SIDS deaths in the period; children were assigned grid references for the address of birth and of death. Data on number of births were abstracted from published material. A log-linear modelling technique was used to investigate the separate effects of age, month of death and month of birth on the risk of SIDS. The Knox method was used to investigate space time clustering of deaths and of births of children who died of SIDS. Separate, statistically significant effects were found for age, month of death and month of birth. There was minor space time clustering of SIDS births and deaths at large time and space intervals, and a marked space time clustering of births in short space time intervals in the first quarter of the year. The finding of an effect of month of birth on the risk of SIDS, and of space time clustering of births suggest that a perinatal hazard--possibly of infectious origin--may play a role in the aetiology of SIDS.     

Increased limb salvage with intraoperative and postoperative ankle level urokinase infusion in acute lower extremity ischemia.

Over a 30-month period (May 1988 to November 1990) 143 acutely ischemic lower extremities (126 patients) were treated with an aggressive surgical approach that included ankle level tibial-peroneal artery thromboembolectomy. Twelve lower extremities in 10 patients that remained ischemic were further treated with adjuvant ankle level urokinase infusion. Sixteen ankle level arteries in 12 extremities were infused with an intraoperative bolus (1 to 2) of urokinase (50,000 to 100,000 units). Continuous postoperative urokinase (25,000 to 50,000 units per catheter per hour x 1 to 5 days) was infused through ankle level arteriotomies in 10 extremities (14 arteries) that did not improve with the initial intraoperative bolus. Concomitant bypass grafting was necessary in four extremities. With adequate inflow established, adjuvant ankle level urokinase salvaged all 12 extremities. The mean increase in ankle/brachial pressure index was 0.84. During continuous postoperative urokinase infusion, lower extremity bleeding requiring blood transfusion occurred in four patients (50%). No deaths occurred in the operative period. Although rhabdomyolysis occurred in 90% of patients, no patients had renal insufficiency. The addition of ankle level urokinase delivery increased the potential limb salvage from 90% of the entire 143 extremities treated during this period to an actual limb salvage of 98%. A mean follow up of 13 months (6 to 36 months) identified one late amputation. Despite the demanding postoperative management required in these patients and the frequent need for early reoperation, the limb salvage obtained justifies this aggressive adjuvant technique in the management of the acutely ischemic lower extremity.