Biomedical subjects
Publications and source records attributed to A Knight.
Stress ulceration is common in patients receiving intensive care. Its cause is ill defined, life threatening complications are rare but the use of H2 antagonists and antacids in prophylaxis is widespread. The development of haemorrhage and perforation appears to be related to a group of risk factors of which sepsis may be the most important.
Astemizole, a new histamine H1 receptor blocker, was compared with placebo in an eight week, double-blind trial in the treatment of seasonal allergic rhinitis. Sixty-five patients of either sex were randomized to either astemizole (32 patients: 10 mg t.i.d. on day 1, 10 mg b.i.d. on day 2, 10 mg o.d. for the remainder of the study) or placebo (33 patients). Patients were seen bi-weekly and maintained a daily diary record of symptoms throughout the study. Significantly more patients in the placebo group (12) compared to the astemizole group (2) dropped out of the study due to treatment failure (p less than 0.05). Astemizole significantly reduced the frequency and severity of allergic symptoms. In subjective evaluations of each treatment by both the investigator and the patients, astemizole was judged good to excellent by 68% compared to 30% for placebo (p less than 0.05). One patient in each group experienced drowsiness. The only significant side effect of astemizole was weight gain (20 patients compared to 1 in the placebo group), although only one patient discontinued astemizole for this reason.
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The effects of a 48 h infusion of arginine vasopressin (AVP) were measured in five separate studies on four normal salt-restricted physicians, in whom fluid retention was prevented. The infusion was associated with an increase in renal sodium excretion which continued during the 24 h after the infusion had been discontinued. During the infusion plasma renin activity (PRA), plasma aldosterone and noradrenaline, and packed cell volume (PCV) fell; glomerular filtration rate, assessed by endogenous creatinine clearance, increased. The findings are best explained by a vasopressin-induced increase in plasma volume, which in the absence of fluid retention is likely to have been due to a redistribution of body water.
Some autoimmune diseases tend to cluster within families, patients with one such disease showing an increased tendency to develop certain other autoimmune diseases within the same group. We have investigated the possibility that this clustering arises because some patients produce autoantibodies which cross-react with antigenic determinants which are shared by diverse tissues. Our data indicate that this is not the case, at least so far as thyroid and gastric autoimmune diseases are concerned. This observation increases the likelihood that the real explanation for such clustering concerns sharing of idiotypic determinants by the different pathogenic clones involved or by their precursors.
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The question of whether autoimmune reactions result from abnormality of the autoantigen or of the autoantibody is fundamental. When reaction of the thyroid stimulating autoantibodies (TSaab) of Graves' disease with their autoantigen is measured in the mouse bioassay which has a very sensitive dose-response curve this provides a favourable system for detecting any influence of allotypic variation in the autoantigen on the affinity of the corresponding autoantibodies. Seven high potency long acting thyroid stimulator (LATS) sera were tested for degree of neutralization by soluble extracts from nine thyroids, using the mouse bioassay to measure changes in LATS activity. The thyroid extracts differed in neutralizing potency and the LATS sera differed in susceptibility to neutralization, but these variations were consistent enough to enable ranking and there were no significant exceptions from especially strong or weak reactions between any individual thyroid extract and any individual LATS serum. Even autologous reactants had no greater or lesser affinity than homologous ones. Five LATS protector (LATSP) sera, tested against six thyroid extracts, including their own, again showed no evidence of allotypic variation in the autoantigen, nor did 55 LATSP sera tested with one of four thyroid extracts. Altogether we have looked at over 200 individual reactions between soluble thyroid antigen and thyroid stimulating autoantibody (LATS and LATSP). We have not found a single significant instance of any exceptionally strong or weak affinities, even with autologous antigen. The findings are in accord with Burnet's theory that autoimmune reactions are due to the emergence of forbidden clones of lymphocytes, reactive with normal self antigens.
Thirty-five patients with perennial rhinitis were treated with beclomethasone dipropionate nasal aerosol three times daily for 48 weeks. There was no evidence at the end of the study of any adverse effects from the topical steroid as assessed by biopsy studies of the nasal mucus membrane and by negative nasal cultures for C. albicans.
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Percoll gradient centrifugation has been applied to Plasmodium falciparum- and P. yoelii-infected blood to allow rapid concentration of gametocytes. In the case of cultured P. falciparum, stage IV and V gametocytes were separated from immature stage II and III forms and concentrated from initial gametocytaemias of 1 to 3% to an average of greater than 80% and a maximum of 100% purity in a fraction which collected at the 1.064/1.083 g/ml interface; the rounded gametocytes of P. yoelii-infected mouse blood were also concentrated in this fraction. A much larger enrichment in microgametocyte concentration (average of 160-fold) was recorded in a fraction that collected at the 1.047/1.064 g/ml interface. The large increases in gametocyte concentration were paralleled by similarly large increases in exflagellation activity, thus confirming the viability of both preparations.
An extracorporeal dual perfusion system of the whole human placenta was developed using a technique of multiple blunt cannulations of the intervillous space. The system was evaluated according to various perfusion-dynamic, metabolic and morphological criteria. Angiographic and dye distribution studies showed 80 to 100 per cent perfusion of the placenta. The perfused organ consumed oxygen, utilized glucose and produced HCG. The flow rates and acid-base values were within acceptable limits. However, problems with high fetoplacental vascular resistance, tendency to metabolic acidosis and fetomaternal fluid transfer were encountered. Ultrastructural studies showed variations in the syncytiotrophoblast and the microvilli.
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Thyroid-stimulating autoantibodies (TSaab) react with the thyrotrophin receptor of the thyroid cells to cause the hyperthyroidism of Graves' disease. Studies using thyroid receptors from various animal species have demonstrated the existence of a fine variation in the specificity of TSaab from various patients. Such variation provides an explanation for the clinical variety seen in some autoimmune diseases and also for the occurrence of inconstant complications such as exophthalmos, chorea, diabetic retinopathy and diabetic nephropathy, which may be based on cross-tissue reactivity.
As part of a study of the effectiveness of beclomethasone dipropionate in perennial rhinitis five immunologically related parameters were measured. These included skin tests, total IgE, specific IgE, nasal and peripheral blood eosinophil counts. In addition, nasal biopsies were obtained in twenty out of sixty patients. It was apparent that patients with perennial rhinitis formed a heterogeneous group who could be divided into three groups based on the extent of immunological abnormality detected. Group 1 consisted of twenty patients who displayed no abnormality in any of the five parameters studied. Group 2 consisted of twenty-six patients in whom specific IgE was not detected but who had varying degrees of abnormal findings in the other laboratory parameters. The remaining fourteen patients formed a third group in whom specific IgE was detected in addition to abnormalities in other parameters. In general, patients with detectable specific IgE had a higher frequency of abnormal parameters, including abnormal histology of their nasal biopsy, than patients in whom no specific IgE was detected. The heterogeneous nature of perennial rhinitis is discussed. Despite the heterogeneous nature of the total patient group, the majority of patients (80%) treated with beclomethasone dipropionate improved compared to 20% improved in the placebo group. There was no difference in the drug effect between the three groups of patients.
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Three patients showing features of both lupus erythematosus and lichen planus are described together with their histological, immunofluorescence and other investigative findings. The similarities between lupus erythematosus and lichen planus are discussed and it is suggested that these may be the result of common pathophysiological pathways.