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Biomedical subjects

W G Reeves

Publications and source records attributed to W G Reeves.

At least 37 records · Page 2Linked to original sources
PubMed1984

Human ultralente insulin.

The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). There was no significant difference between human and bovine insulin in the rise in plasma glucose concentration from 0400 to 0700 after an injection the previous morning and no difference between patients receiving an adequate or insufficient dose of human ultralente insulin. Bovine insulin antibody binding was reduced with human insulin (p less than 0.002), which suggests that human insulin is less antigenic than beef insulin. Once daily human ultralente insulin provides a suitable formulation for the basal insulin requirement of diabetics.

Adult↗
PubMed1984

Factors governing the human immune response to injected insulin.

Seventy-nine patients were observed prospectively during their initial period of treatment with conventional bovine insulins. Insulin antibody levels 6 months after starting insulin therapy did not correlate with age, gender or beta cell function at onset of treatment. Patients who required soluble insulin in addition to isophane insulin developed higher levels of insulin antibody. Patients bearing the HLA-B8, DR3 and C4AQO alleles had lower levels of insulin antibody, whereas those bearing DR7 produced significantly higher levels. Other alleles at the C4A, C4B, C2, factor B or Gm loci did not appear to have a significant effect on insulin antibody production. The hyporesponsiveness of B8/DR3/ C4AQO -positive individuals probably reflects a non-specific abnormality of immunity whereas the enhanced responsiveness of those positive for DR7 suggests the presence of a specific immune response gene for insulin.

Adolescent↗
PubMed1984

A fifteen-month double-blind cross-over study of the efficacy and antigenicity of human and pork insulins.

The antigenicity and efficacy of semi-synthetic human and pancreatic pork insulins have been compared in a double-blind double cross-over study in 96 insulin-treated diabetic patients. Transfer from pork to human insulin was associated with a 1.2 +/- 0.5 mmol/l deterioration (p less than 0.05) in the fasting blood glucose level, while the opposite change caused a 1.1 +/- 0.5 mmol/l improvement (p less than 0.05). After 4 months treatment, glycosylated haemoglobin levels were lower on pork (11.1 +/- 0.3%) than on human (11.7 +/- 0.3% p less than 0.01) insulin. The incidence of hypoglycaemia was similar with the two insulins. IgG insulin antibody levels were identical after human insulin treatment (5.7 +/- 0.4 micrograms/l) compared to pork insulin treatment (5.9 +/- 0.5 micrograms/l). Patients with high levels of antibodies (greater than 10 micrograms/l) showed a similar reduction in level when switched to either species of highly purified insulin. The deterioration in fasting blood glucose control is consistent with similar reports for biosynthetic human insulin and suggests, in the absence of changes in insulin antibody levels, a small but clinically significant pharmacokinetic difference between human and pork insulin.

Adolescent↗
PubMed1984

Comparison of highly purified semi-synthetic insulin and highly purified porcine insulin in the treatment of type I diabetes: interim report of a multi-centre randomised single blind study.

This is an interim report of a long term single-blind study of the effects of changing diabetic patients treated with highly purified porcine insulin to semi-synthetic human insulins of identical formulation. Twenty four insulin dependent diabetics were randomly allocated to continue with porcine insulin (n = 11) or human insulin (n = 13). There were no significant changes within the groups nor differences between the groups in mean preprandial capillary blood glucose, glycosylated haemoglobin or insulin dose during the first 24 weeks of the study. Insulin antibody levels remained low and did not differ between the groups. No local or systemic adverse reactions were observed. In this group of patients conversion to human insulin did not result in a change in diabetic control or insulin dose.

Adolescent↗
PubMed1984

HLA phenotype and insulin antibody production.

HLA phenotypes have been determined in 79 patients as part of a prospective study of factors governing the immune response to injected insulin. IgG insulin antibody levels 6 months after starting treatment with bovine insulin were significantly higher in patients bearing HLA-DR7 and this in conjunction with the lack of a similar pattern in the IgG response to Helix pomatia haemocyanin, suggests the presence of an immune response gene for insulin. The hyporesponsiveness of HLA-B8/DR3/C4AQ0 positive individuals is more likely to reflect a non-specific abnormality of immunity.

Adolescent↗
PubMed1983

Human insulin and porcine insulin in the treatment of diabetic children: comparison of metabolic control and insulin antibody production.

Semisynthetic human insulin and highly purified porcine insulin were compared in a double blind crossover study in 21 diabetic children. Glycosylated haemoglobin values at the end of four month treatment periods were higher after treatment with human insulin than after treatment with porcine insulin (mean 15.7% (SD 2.3%) v 14.2% (2.3%); p less than 0.01). Higher fasting blood glucose concentrations occurred during treatment with human insulin than with porcine insulin (mean 12.0 (SD 2.1) v 11.0 (2.4) mmol/1; mean 216 (SD 38) v 198 (43) mg/100 ml; p less than 0.05), but there were no significant differences at other time points during the day. The incidence of hypoglycaemia was similar for both treatment groups. Concentrations of antibody reactive with porcine and human insulins were similar for the two treatment groups, although greater fluctuation was observed in the amount of antibody reactive with human insulin. Semisynthetic human insulin is safe and effective in diabetic children, although further work is needed to devise regimens which achieve optimal blood glucose control.

Adolescent↗
PubMed1983

Development of clinical immunology and allergy in the UK--common problems and solutions.

Despite major advances in immunological science there is comparatively little expertise in clinical immunology in British medical schools and the health service. There is no logical reason why clinical immunology and allergy should be considered separately and a joint approach toward the correction of these deficiencies is required. The most immediate service needs are for the appointment of more laboratory-based consultant immunologists to develop and coordinate clinical services in each centre in conjunction with organ-based specialists who should receive specific training in immunology. Key developments in the science and technology of immunology point toward novel ways of diagnosing, treating, and preventing immunological disorders. Academic units have an important role in exploiting these basic advances as speedily and effectively as possible and teaching contemporary immunology at undergraduate and postgraduate levels. A reduction in the morbidity of any of the common immunologically-mediated diseases would produce considerably savings for the health service.

Allergy and Immunology↗
PubMed1983

Effects of new insulins on insulin and C-peptide antibodies, insulin dose, and diabetic control.

24 diabetic patients stabilised on conventional bovine insulins and possessing insulin antibodies underwent a study of the immunological and clinical consequences of changes in both purity and species of their insulin preparations. After a 2-month run-in period patients were treated for 3 consecutive 4-month periods with (a) purified bovine insulin (20-40 ppm proinsulin), (b) highly purified porcine insulin, and (c) semisynthetic human insulin, without elective dose changes. Mean insulin antibody levels changed little on purified bovine insulin (22.2 leads to 23.4 micrograms/l) but fell on highly purified porcine (23.4 leads to 12.9 micrograms/l) and remained much the same on Semi-Synthetic human insulin. In contrast, C-peptide antibodies fell significantly and continuously throughout the study. The slower rate of fall in C-peptide antibody levels is likely to be due to the prolonged half-life of circulating exogenous proinsulin in the presence of insulin antibody. Although insulin dose remained constant the incidence of hypoglycaemic episodes did not increase and glycosylated haemoglobin levels rose significantly when patients were on porcine insulin. The deterioration in diabetic control may have been due to greater temporal mismatch between insulin needs and insulin availability with pork or human insulin than with beef insulins, and to reduced insulin antibody levels. The use of purer insulins which more closely resemble the human form can cause a significant reduction in levels of insulin and C-peptide antibodies. Although these changes may have other benefits they do not necessarily produce better diabetic control. Subcutaneous insulin regimens need to be tailored to the individual patient and, indirectly, to his antibody status.

Animals↗
PubMed1983

The stimulation of superoxide anion production in guinea-pig peritoneal macrophages and neutrophils by phorbol myristate acetate, opsonized zymosan and IgG2-containing soluble immune complexes.

The kinetics of superoxide anion production in guinea-pig peritoneal macrophages and neutrophils were determined following in vitro stimulation with phorbol myristate acetate (PMA), opsonized zymosan (OZ) and soluble immune complexes of guinea-pig IgG2 (SIC). Superoxide production was recorded as chemiluminescence (CL) arising from the reductive cleavage of lucigenin. With PMA, both macrophages and neutrophils displayed a two-phase response consisting of a rapid initial burst of CL, which preceded ligand ingestion, followed by a plateau in the CL response which persisted for more than 30 min. By contrast, OZ induced a slow progressive increase in CL in both phagocytes which was consistent with the development of an oxidative burst concomitant with ingestion. The phagocytes differed in their responses to SIC, the macrophages displaying CL kinetics similar to those observed with PMA, whereas the neutrophils responded in the manner observed with OZ. The relationship between disparity in the patterns of macrophage and neutrophil CL responses to SIC and differences in their expression of Fc receptors for IgG2 (Coupland & Leslie, 1983) is discussed.

Animals↗
PubMed1982

The effect of insulin antibodies on insulin dose and diabetic control.

In a single blind randomised cross-over study, 40 patients were changed from ordinary bovine to highly purified porcine insulins for a period of 6 months. Half were later rechallenged with bovine insulin. Sequential determinations of IgG insulin binding capacity for bovine insulin were correlated with insulin dose and diabetic control. After changing to highly purified insulins the following correlations were observed between percentage change in insulin dose and change in insulin binding capacity: at 2 months r = 0.35 (p less than 0.05), at 4 months r = 0.38 (p less than 0.02) and at 6 months r = 0.37 (p less than 0.02). When the patients who showed substantial changes in HbA1 were removed from the analysis, the remaining 29 demonstrated a clearer relationship between these two variables (r = 0.56, p less than 0.01). Removal of patients with a low initial insulin binding capacity left 18 patients with stable diabetes, and changes in insulin binding capacity and insulin dose showed an even closer correlation for this group (r = 0.77, p less than 0.001). A similar degree of positive correlation was observed after rechallenge with bovine insulin. We conclude that the level of circulating insulin antibody affects the dose of insulin required to maintain stable diabetic control.

Adolescent↗
PubMed1982

Insulin antibodies induced by bovine insulin therapy.

Insulin antibodies are detectable in the sera of most patients within 3-4 months of starting treatment with conventional bovine insulins. Various factors determine the immunogenicity of insulin preparations including the genetic background of the recipient. This causes wide variation in response. Solid phase absorption studies as well as competitive binding in fluid phase indicate that the antibodies formed are almost always specific for determinants shared by the endogenous human molecule. This has important implications for the metabolic effect of insulin antibodies in vivo as well as for mechanisms of autoantibody production in man.

Animals↗
PubMed1982

C-peptide antibodies induced by bovine insulin therapy.

Antibodies reactive with the C-peptide portion of proinsulin can be detected in the sera of patients on conventional bovine insulin regimes which include the soluble form. Direct and competitive binding studies demonstrate that C-peptide antibodies show species specificity but do not recognize free homologous C-peptide. This is likely to be due to conformational change following cleavage of C-peptide from the proinsulin molecule. Examination of sera from a large group of patients established on a standard insulin regime shows that C-peptide and insulin antibody levels do not correlate with each other and are likely to show different patterns of genetic control.

Animals↗
PubMed1982

Human monocyte binding of homologous monomer and complexed IgG.

Human peripheral blood monocyte binding of homologous IgG has been studied using monomer and covalently cross-linked dimer and trimer. A competitive radioassay using enriched monocytes was employed to determine the association constant (Ka) and the number of receptor sites per cell. Monomer and dimer bound with very similar Ka values (7.15 X 10(7) and 7.14 X 10(7)LM-1) whereas a slightly higher figure was obtained with trimer (8.9 X 10(7)LM-1). The number of receptor sites for dimer and trimer (90.5 and 107.5 X 10(3)/cell, respectively) were much greater than for monomer (14.5 X 10(3)/cell). Inhibition of dimer and trimer binding by monomer gave heterogenous Scatchard plots, each with two components. These findings suggest that human peripheral blood monocytes possess two types of Fc receptor, one of high affinity binding monomer and complexes and one of low affinity which predominantly binds complexes.

Biopolymers↗
PubMed1982

Familial Hibernian fever.

An Irish family with an unusual periodic syndrome is described. Attacks consist of fever with localized myalgia and painful erythema. Other features include abdominal pain and pleurisy, with leucocytosis and a high ESR. The syndrome resembles classical familial Mediterranean fever (FMF) but differs from it in its prompt response to steroids and its autosomal dominant pattern of inheritance. The disease appears to have a benign course and no patient has developed amyloid.

Adult↗
PubMed1981

Neutrophil function in chronic liver disease.

Neutrophil locomotion, phagocytosis and killing of Candida albicans, and plasma opsonization of brewer's yeast were studied in 44 out-patients with chronic liver disease. There were four diagnostic groups: alcoholic liver disease (ALD), chronic active hepatitis (CAH), primary biliary cirrhosis (PBC) and cryptogenic cirrhosis (CC). Results were compared with a control group of patients with non-malignant disorders of the upper alimentary tract. Neutrophil locomotion induced by zymosan-activated autologous plasma was significantly depressed in patients with ALD and, to a lesser extent, in cryptogenic cirrhosis. With plasma from healthy donors, the patients' neutrophils showed normal locomotion. Plasma from patients with CAH gave slightly but significantly reduced phagocytosis of both Candida albicans and brewer's yeast, but the patients' cells had normal phagocytic and killing activity in the presence of normal plasma. Thus, no intrinsic abnormality in neutrophil function was found in these patients, but plasma defects, which differed in cirrhoses of different underlying aetiology, led to impaired neutrophil locomotion or phagocytosis. No correlations were found between these plasma defects and circulating levels of C3, C4, immune complexes or IgA.

Adolescent↗