Showing papers by "John Radcliffe Hospital published in 1980"
TL;DR: Unlike many previous trials which had negative results, in this trial the drug was given intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.
308 citations
TL;DR: A speculative hypothesis for the mechanisms involved in the B-cell responses to glucose is out lined because the observed correlations between rates of metabolism and insulin release and biosynthesis are consistent with the substrate-site hypothesis.
Abstract: The models proposed for the means whereby the B-cell recognises glucose and related compounds as signals for insulin release and biosynthesis are discussed. The observed correlations between rates of metabolism and insulin release and biosynthesis are consistent with the substrate-site hypothesis. For glucose itself, the enzymes catalysing the phosphorylation of the sugar provide an explanation for the major characteristics of the islet responses, but for N-acetylglucosamine evidence is presented that the sugar transport system fulfils this discriminatory role. Possible mechanisms whereby sugar metabolism may be linked to changes in Ca2+-handling are considered and evidence is given supporting a role for the cytosolic NADPH/NADP+ ratio and the islet content of phosphoenolpyruvate. The nature of the targets for cyclic AMP and Ca2+ is discussed and some properties of islet cAMP-dependent protein kinase are summarised. Evidence is presented for the presence of calmodulin in islets and the possible involvement of calmodulin in stimulussecretion coupling. On the basis of these considerations a speculative hypothesis for the mechanisms involved in the B-cell responses to glucose is out lined.
244 citations
TL;DR: Patients in a transplant unit diagnosed in two patients having occupied the same postoperative cubicle shortly before onset of their illnesses had Legionnaires' disease, and water taken from the cubicle shower bath and from other showers in the unit was treated with chlorine.
232 citations
TL;DR: In 92 women complaining of heavy but regular periods for which no cause was found, the relation was studied between measured menstrual blood loss during two consecutive periods and the patient's subjective assessment of blood loss, the number of days of bleeding, and thenumber of sanitary pads and tampons used.
226 citations
TL;DR: The monoclonal antibody (F10–89–4) described in this study recognizes an antigen which by quantitative absorption analysis is absent from human brain, kidney, liver, heart, erythrocytes, platelets and normal serum, but is present on spleen, lymph node, chronic lymphatic leukemia cells, bone marrow, thymus and granulocytes.
Abstract: The monoclonal antibody (F10–89–4) described in this study recognizes an antigen which by quantitative absorption analysis is absent from human brain, kidney, liver, heart, erythrocytes, platelets and normal serum, but is present on spleen, lymph node, chronic lymphatic leukemia cells, bone marrow, thymus and granulocytes at a ratio of 1 : 1 : 0.8 : 0.3 : 0.3 : 0.1, respectively. Analysis with the fluorescence-activated cell sorter showed that 100% of thymocytes, lymph node lymphocytes, blood mononuclear cells and granulocytes carry the antigen, while 83% of bone marrow cells are positive. There was marked heterogeneity in the amount of labeling of thymocytes, with 3 major peaks. There was also heterogeneity of labeling of blood mononuclear cells and lymph node lymphocytes, with a weakly staining hump containing approximately 20% of the cells in the case of lymph node lymphocytes. Double labeling experiments demonstrated that the weakly staining cells of blood and lymph node were B lymphocytes, while frozen sections of thymus showed that the antigen was expressed most weakly in subcapsular cortical thymocytes, and most strongly on medullary thymocytes. Biochemical studies established that the antigen bound to lentil lectin columns, and sodium dodecyl sulfate polyacrylamide gel electrophoresis studies using NaB3 H4-labeled blood mononuclear cells established that the antigen was a major glycoprotein of lymphocytes, and that its molecular weight was in the region of 190 000 to 215 000.
213 citations
TL;DR: The monoclonal antibody (F10–44–2) described in this report recognizes an antigen which by quantitative absorption analysis is found predominantly on spleen, lymph node, bone marrow, thymus, granulocytes and brain, the amount of antigen on these tissues being approximately the same within a factor of 2 or 3.
Abstract: The monoclonal antibody (F 10-44-2) described in this report recognizes an antigen which by quantitative absorption analysis is found predominantly on spleen, lymph node, bone marrow, thymus, granulocytes and brain, the amount of antigen on these tissues being approximately the same within a factor of 2 or 3. Analysis with the fluorescence-activated cell sorter showed that 29% of thymus cells, 61% of bone marrow cells, 95% of blood mononuclear cells, 98% of lymph node lymphocytes and 100% of granulocytes carried the antigen. With blood mononuclear cells and lymph node lymphocytes, there were two distinct peaks, with one peak labeling very weakly. Double labeling experiments established that the weakly labeled peak contained the B lymphocytes. Studies on frozen sections of thymus established that positive thymocytes were found only in the medulla indicating that the antigen appears late in T lymphocyte maturation. The lymphatic nodules (B lymphocyte areas) of spleen and lymph node appeared virtually negative on frozen sections showing that there was too little antigen on the B lymphocyte surface for confident detection by fluorescence microscopy. Sodium dodecyl sulfate polyacrylamide gel eletrophoresis of NaB3H4-labeled blood mononuclear cells established that the antigen was a major glycoprotein of the leukocyte membrane and that its mol. wt. was 105000. This antigen shows a striking similarity in biochemistry and tissue distribution to the W 3/13 antigen of the rat and is likely to be the human homologue of this antigen.
179 citations
TL;DR: A Welsh family in which three members have five α-globin genes—three on one chromosome and two on the other and the additional α gene results in an increased α mRNA output and it may therefore produce the phenotype of mild β-thalassaemia.
Abstract: The human genome has two linked α-globin genes on chromosome 16. Deletion of one or more of them, as occurs in α-thalassaemia, leads to a reduced output of α-globin mRNA in proportion to the number of α-globin genes lost1. In some racial groups deletion of one of the pair of α-globin genes may result from unequal crossing over between the genes on homologous chromosomes2,3 by a mechanism resembling that postulated for the formation of the δβ fusion genes of the Lepore haemoglobins4. By analogy, the opposite chromosome in this cross-over should have three α-globin genes just as the ‘anti-Lepore’ chromosome has three non-α-chain genes. We describe here a Welsh family in which three members have five α-globin genes—three on one chromosome and two on the other. The additional α gene results in an increased α mRNA output and it may therefore produce the phenotype of mild β-thalassaemia.
126 citations
TL;DR: The results indicate that reticulocytes and young red cells are more susceptible to invasion by this parasite as compared with metabolically older cell populations, contrary to the current belief that red cells of all ages are invaded indiscriminately by P. falciparum.
Abstract: Summary The relationship between red cell age and susceptibility to invasion by the malarial parasite Plasmodium falciparum has been examined by several different methods including short-term cultures of parasitized human blood. The results indicate that reticulocytes and young red cells are more susceptible to invasion by this parasite as compared with metabolically older cell populations. This is contrary to the current belief that red cells of all ages are invaded indiscriminately by P. falciparum.
This observation has important theoretical, clinical and practical implications; its mechanism remains as yet unclear.
119 citations
[...]
98 citations
TL;DR: β-Hydroxysteroid dehydrogenase activity was studied in homogenates of placenta, fetal membranes and decidua obtained at term, using cortisol and cortisone as substrates to study the dependence of activity on pH, substrate and enzyme concentration and the inhibitory effect of other steroids.
96 citations
TL;DR: It is concluded that maternal hypertension is associated with slight developmental delay in early childhood and there are some indications that treatment with methyldopa may reduce this effect.
TL;DR: Haemoglobin E is studied and it is shown that the βE chain is inefficiently synthesized and produces the phenotype of a mild form of β thalassaemia; hence, when inherited together with α2β226GlU→Lys it causes a marked β-chain deficit.
Abstract: Haemoglobin E (alpha 2 beta 2(26)Glu leads to Lys) is one of the commonest haemoglobin variants. There are an estimated 30 million carriers of the beta E gene in South-East Asia, where they comprise more than 50% of the population in some areas; however, the reasons for this high frequency have never been adequately explained. Homozygotes for HbE may be midly anaemic, but they do not have any clinical disability. However, individuals heterozygous for both beta E and beta thalassaemia (HbE/beta thalassaemia) have a severe clinical disorder which in some cases may approach that seen in homozygous beta thalassaemia and which is by far the commonest form of symptomatic thalassaemia in the Indian subcontinent and South-East Asia. Haemoglobin E is the only common structural variant which interacts with beta thalassaemia to produce a severe disorder and the underlying mechanism of the interaction is not known. We have studied several homozygotes and heterozygotes for HbE and show here that the beta E chain is inefficiently synthesized and produces the phenotype of a mild form of beta thalassaemia; hence, when inherited together with beta thalassaemia it causes a marked beta-chain deficit. Furthermore, the mechanism for the defective production of beta E chains seems to be a reduction of beta E mRNA, a most unexpected finding in a disorder caused by a single amino acid substitution and presumably by a single nucleotide change in the DNA of the beta globin gene.
TL;DR: DR matching seems to improve graft survival even in patients who have never been transfused or not, and matching for the limited number of DR antigens mostly with a relatively high antigen frequency should simplify the matching procedure for selection of donor-recipient pairs in cadaveric transplantation.
TL;DR: The results suggest that islet phosphodiesterase-stimulating activity is similar to, although not necessarily identical with, calmodulin from skeletal muscle; that is let calmod insulin may play an important role in Ca(2+)-dependent stimulus-secretion coupling in the beta-cell; and that calmodoxin may exert part at least of its effect on secretion via phosphorylation of endogenous islet proteins.
Abstract: 1. The ability of a range of phenothiazines to inhibit activation of brain phosphodiesterase by purified calmodulin was studied. Trifluoperazine, prochlorperazine and 8-hydroxyprochlorperazine produced equipotent dose-dependent inhibition with half-maximum inhibition at 12mum. When tested at 10 or 50mum, 7-hydroxyprochlorperazine was a similarly potent inhibitor. However, trifluoperazine-5-oxide and N-methyl-2-(trifluoromethyl)phenothiazine were ineffective at concentrations up to 50mum, and produced only a modest inhibition at 100mum. 2. The same phenothiazines were tested for their ability to inhibit activation of brain phosphodiesterase by boiled extracts of rat islets of Langerhans. At a concentration of 20mum, 70-80% inhibition was observed with trifluoperazine, prochlorperazine, 7-hydroxyprochlorperazine or 8-hydroxyprochlorperazine, whereas trifluoperazine-5-oxide and N-methyl-2-(trifluoromethyl)phenothiazine were less effective. 3. The effect of these phenothiazines on insulin release from pancreatic islets was studied in batch-type incubations. Insulin release stimulated by glucose (20mm) was markedly inhibited by 10mum-trifluoperazine or -prochlorperazine and further inhibited at a concentration of 20mum. 8-Hydroxyprochlorperazine (20mum) was also a potent inhibitor but 7-hydroxyprochlorperazine (20mum) elicited only a modest inhibition of glucose-stimulated insulin release; no inhibition was observed with trifluoperazine-5-oxide or N-methyl-2-(trifluoromethyl)phenothiazine. 4. Trifluoperazine (20mum) markedly inhibited insulin release stimulated by leucine or 4-methyl-2-oxopentanoate in the absence of glucose, and both trifluoperazine and prochlorperazine (20mum) decreased insulin release stimulated by glibenclamide in the presence of 3.3mm-glucose. 5. None of the phenothiazines affected basal insulin release in the presence of 2mm-glucose. 6. Trifluoperazine (20mum) did not inhibit islet glucose utilization nor the incorporation of [(3)H]leucine into (pro)insulin or total islet protein. 7. Islet extracts catalysed the incorporation of (32)P from [gamma-(32)P]ATP into endogenous protein substrates. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis resolved several phosphorylated bands, but incorporation was slight. However, calmodulin in the presence of Ca(2+) greatly enhanced incorporation: the predominant phosphorylated band had an estimated mol.wt. of 55000. This enhanced incorporation was abolished by trifluoperazine, but not by cyclic AMP-dependent protein kinase inhibitor protein. 8. These results suggest that islet phosphodiesterase-stimulating activity is similar to, although not necessarily identical with, calmodulin from skeletal muscle; that islet calmodulin may play an important role in Ca(2+)-dependent stimulus-secretion coupling in the beta-cell; and that calmodulin may exert part at least of its effect on secretion via phosphorylation of endogenous islet proteins.
TL;DR: The results suggest that 200 mg danazol daily is the most acceptable regimen clinically since it significantly reduced menstrual blood loss and was associated with a relatively low incidence of side effects.
TL;DR: In those patients who had clinical attacks of ulcerative colitis at the start of the study, symptomatic improvement was commoner in the group treated with Ac-5-ASA enemas than in those who received placebo therapy.
Abstract: In a double-blind controlled therapeutic trial, retention enemas of N-acetyl-5-aminosalicylic acid (Ac-5-ASA) were compared with dummy enemas in the treatment of active ulcerative colitis. Forty patients were studied, each patient taking one test enema twice a day for 2 weeks. Seventeen of the patients had a mild clinical attack of the disease; the 23 others had sigmoidoscopic evidence of active inflammation although they were in clinical remission. Histological and sigmoidoscopic improvement were significantly commoner in the patients receiving the active treatment than in those taking the dummy preparation. Pronounced histological improvement was only seen in patients taking the Ac-5-ASA enemas. In those patients who had clinical attacks of ulcerative colitis at the start of the study, symptomatic improvement was commoner in the group treated with Ac-5-ASA enemas than in those who received placebo therapy. Ac-5-ASA resembles 5-aminosalicylic acid in its effect on the inflamed mucosa in ulcerative colitis. Further studies into other substituted salicylates may lead to the development of an effective oral agent that does not carry the side effects associated with the sulphapyridine moiety of sulphasalazine.
TL;DR: Preparations incorporating 90 per cent ethanol are recommended as hand disinfectants with a broad virucidal activity, and Methanol and ethanol were the only alcohols of those tested that reduced the titres of the more resistant astrovirus and echovirus 11, and then only when used at high concentrations.
TL;DR: Human breast milk of high and low fat content was fed to babies aged 4-9 days from bottles and changes in fat content parallel to those found during the course of a breast-feed did not alter either milk intake rate or sucking patterns.
TL;DR: Fetal outcome in 98 patients with spontaneous antepartum late decelerations was studied by combining the data of two obstetric departments and the results were compared with those of oxytocin contraction stress tests.
TL;DR: Fetal haemoglobin (Hb F) synthesis has been studied in 22 cases of sickle cell anaemia from Saudi Arabia and compared with an equal number of cases of African origin, indicating that the selective survival of Hb F containing cells (F cells) was an important factor in determining the final H b F levels.
Abstract: Fetal haemoglobin (Hb F) synthesis has been studied in 22 cases of sickle cell anemia (SS) from Saudi Arabia and compared with an equal number of cases of African origin. Among the Saudi Arabs gamma chain synthesis ranged from 4.0% to 19.9% of the total non-alpha chain synthesis (mean 8.1%) while the corresponding range for the Negro cases was < 0.3% to 4.6% (mean 1.7%). In both groups the peripheral blood Hb F level was on average 3--4 times higher than the proportion synthesized, indicating that the selective survival of Hb F containing cells (F cells) was an important factor in determining the final Hb F levels. Among the Saudi Arab cases there was a significant negative correlation between the degree of F cell enrichment and either the Hb F level of the percentage gamma chain synthesis. No such correlation was observed among the Negro cases. A high proportion of the cases in both groups were carriers of alpha thalassaemia in addition to SS, but no effect of alpha thalassaemia on Hb F production was observed.
TL;DR: Islets of Langerhans were isolated by collagenase digestion from the pancreas of a 39 year-old female renal transplant donor and subjected to three consecutive periods of tissue culture, after each of which they were incubated in vitro with various agents whose effects on insulin release from islets of laboratory animals have previously been established.
Abstract: Islets of Langerhans were isolated by collagenase digestion from the pancreas of a 39 year-old female renal transplant donor. The islets were subjected to three consecutive periods of tissue culture, after each of which they were incubated in vitro with various agents whose effects on insulin release from islets of laboratory animals have previously been established. After the first culture period, the basal insulin secretion rate of 5.2 μU/islet/h seen with 2 mmol/l glucose was increased approx. 5-fold on raising the glucose concentration to 20 mmol/l. The islets retained the insulin-secretory response to 20 mmol/l glucose throughout the period of study. Insulin secretion was also stimulated by mannose, leucine, α-ketoisocaproate, dihydroxyacetone and 3-hydroxybutyrate, but not by fructose or N-acetyl-glucosamine. Fructose however increased insulin release in the presence of 4 mmol/l glucose. Caffeine elicited insulin release in the absence of glucose and enhanced insulin release in response to 10 mmol/l glucose. Glucose-stimulated insulin release was inhibited by trifluoperazine (25 μmol/l).
TL;DR: The radiological features of Crohn's disease of the small intestine are described in a report on 100 patients examined by a barium infusion method and a multiplicity of radiological signs were seen in the majority of the examinations.
TL;DR: The effect of a traditional (Mexican Hat) and of a new (Thin Latex) nipple shield on the sucking patterns and milk intake of 5-8-day-old babies was examined.
TL;DR: This review will concentrate on the restriction of human cytotoxic T lymphocyte (CTL) function by the HLA complex, concerned with the recognition, by T lymphocytes, of cell surfaces that differ slightly from self.
Abstract: The human major histocompatibility complex (MHC), the HLA system, has been extensively analysed because of its role in organ graft rejection, and the recent demonstration that many of its alleles contribute to disease susceptibility. The relationship with disease is unlikely to be accidental and probably relates to the biological function of this group of linked genes. The murine equivalent of HLA, the H2 system, has been shown to regulate immune responses by controlling immunocyte interactions [5, 44, 55, 57, 77]. It is pertinent, therefore, to determine whether the HLA system functions in this way. There is accumulating experimental evidence that this is so [7, 25, 34, 37, 65] and this review will concentrate on one aspect; the restriction of human cytotoxic T lymphocyte (CTL) function by the HLA complex. It is concerned with the recognition, by T lymphocytes, of cell surfaces that differ slightly from self. These differences can be minor transplantation antigens [34], changes consequent on chemical alteration [25, 68], or virus infection [34, 47, 50, 70]. These may all be models for changes in cells that could occur in human disease due to somatic mutation, toxins, or infection.
TL;DR: An indirect immunoperoxidase technique was used to demonstrate fibronectin in sections of routine formalin fixed paraffin embedded renal tissue to demonstrate antigenicity of fibronectionin previously masked by fixation and embedding procedures.
Abstract: An indirect immunoperoxidase technique was used to demonstrate fibronectin in sections of routine formalin fixed paraffin embedded renal tissue. Previous exposure of the sections to a solution of pepsin (4 mg/ml) in 0.01 N HCl for 2 h at 37° C was essential in order to demonstrate antigenicity of fibronectin previously masked by fixation and embedding procedures.
TL;DR: The specific treatment of hypertension in pregnancy is still a matter of dispute and some obstetricians never use antihypertensive treatment in the management of even severe preeclampsia, while in the United States peirenteral magnesium sulphate is the first line of treatment.
TL;DR: Captopril and frusemide controlled blood pressure in all 10 patients with severe refractory hypertension, without side effects in 9, and there was a significant rise in plasma-potassium in 9 patients, and hyperkalaemia developed in 3 patients despite coincident treatment with frusemides.
TL;DR: It is the opinion that single-stage proctocolectomy is the operation of choice in the great majority of patients with ulcerative colitis and in patients with long-standing disease in whom there are factors associated with a high risk of developing cancer of the large bowel.
Abstract: The majority of patients with ulcerative colitis can be managed satisfactorily throughout their lives by medical treatment, but a minority require colectomy. In severe attacks, emergency surgery is often required to save the patient's life. In chronic disease not responding well to medical treatment, elective colectomy will restore the patient to good health. Colectomy is also necessary for certain local complications, such as cancer, severe fistulas, and strictures. Prophylactic colectomy is indicated in patients with long-standing disease in whom there are factors associated with a high risk of developing cancer of the large bowel. For all these indications, it is our opinion that single-stage proctocolectomy is the operation of choice in the great majority of patients. Finally, we consider that the best results are obtained when the physician and the surgeon work together in the closest possible cooperation.
TL;DR: Here Andrew McMichael and Judy Bastin concentrate on the potential value of monoclonal antibodies in clinical medicine, surveying papers published up to June 1980, and a number of preprints and personal communications.