Quarterly communicable disease review. July to September 1992. From the PHLS Communicable Disease Surveillance Centre.
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Biomedical subjects
Publications and source records attributed to W G Reeves.
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Subgingival restorative margins are associated with the development of plaque-related inflammatory periodontal disease, primarily because of a shift in the subgingival microflora from a profile associated with health to one associated with disease. The degree and extent of the marginal inflammation is influenced by four factors: failure to maintain proper emergence profile, inability to adequately finish and/or close subgingival margins, placement of subgingival margins in an area with minimum to no attached gingiva, and violation of the biologic width. Supragingival margin placement is the location of choice for all restorative margins to avoid iatrogenic periodontal disease. However, consideration of these four factors will help reduce the adverse impact of restorative margins that must be carried subgingivally.
We have developed an in vitro priming assay in which peripheral blood lymphocytes from normal subjects are primed with insulin for 14 days prior to challenge with insulin in conjunction with autologous antigen-presenting cells for a further 5 days. Sheep, beef and pork insulins possess, respectively, four, three and one amino acid differences from the human molecule (out of a total of 51 residues) and the magnitude of the response to priming correlates with the degree of sequence variation. Although human insulin produces little response, priming with heterologous insulins readily induces auto-immunization on secondary challenge. The response to porcine priming was enhanced if the secondary cultures were challenged with bovine or ovine insulin, i.e., a heteroclitic response was observed. Individual donors differ in their response to priming and high responders possess the HLA-DR7 glycoprotein more frequently than low responders. This is in keeping with previous studies on antibody production in vivo and probably relates to the ease with which individual class II glycoproteins complex with processed antigen and stimulate T cells. This method has considerable potential for screening novel insulin molecules and formulations and should facilitate the mapping of helper and suppressor epitopes as well as the identification of agretopes involved in the presentation of insulin to T cells.
The composition of plume produced during carbon dioxide laser endoscopic treatment for endometriosis was examined to determine whether it represented a hazard to the surgical staff. A total of 32 plume samples were collected from 17 women undergoing laser laparoscopic treatment for endometriosis and/or adhesions. The smoke was found to consist of particles having a median aerodynamic diameter of 0.31 micron with a range of 0.10-0.80 micron. The size range has two consequences: 1) using a human red blood cell as a model for all cells, it can be stated with greater than 99.9999% certainty that no cell-size particles, including cancer cells, are present in the plume; 2) particles in this size range are too small to be effectively filtered by currently available surgical masks.
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Neutrophil phagocytosis and killing of Candida albicans were examined using a radiometric assay in 25 patients with insulin-dependent diabetes and 17 controls under various in vitro metabolic conditions. Glucose was present at 5, 10 and 50 mM, beta-hydroxybutyrate at 1, 5 and 20 mM and glucose with beta-hydroxybutyrate in combinations of 10 with 5 and 50 with 20 mM, respectively. Phagocytosis occurred at similar levels in diabetics and controls at all the glucose and beta-hydroxybutyrate concentrations used. The ability to neutrophils from diabetics to kill candida was inhibited by increased concentrations of glucose and beta-hydroxybutyrate, both independently and in combination. Candida killing (mean +/- s.e.) was 20 +/- 2.4, 19 +/- 2.3 and 13 +/- 2.7% at glucose concentrations of 5, 10 and 50 mM; and 20 +/- 3.4, 20 +/- 3 and 13 +/- 3% at beta-hydroxybutyrate concentrations of 1, 5 and 20 mM, respectively, and in glucose and beta-hydroxybutyrate combinations of 10 with 5 and 50 with 20 mM was 20 +/- 2.8 and 10 +/- 2.8%, respectively. Inhibition was not observed with control neutrophils. These data indicate that although phagocytosis occurs at similar levels in diabetics and controls, killing of candida by the diabetic neutrophil is impaired under conditions of hyperglycaemia and ketosis. The biochemical basis for this effect is discussed.
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A new method for the measurement of phagocytosis of Candida albicans by human polymorphonuclear leucocytes (PMN) is described using a fluorescence activated cell sorter. We have used acridine orange to discriminate between PMN which have internalised yeast particles and those which have not. This method allows accurate measurement of particle phagocytosis as an event distinct from particle adherence. It also permits detailed examination of the kinetics of phagocytosis, the study of which is likely to be of value in the investigation of diseases where abnormalities of PMN function are suspected.
Twenty-six Type 1 diabetic patients previously treated for 10-20 months with twice daily conventional bovine isophane insulin (containing at least 1000 ppm proinsulin) were changed to highly purified (less than 1 ppm proinsulin) bovine isophane for 6 months (Switch group). Insulin antibody levels fell significantly from a geometric mean of 14.9 to 9.1 micrograms/l. Thirty-two patients with newly diagnosed Type 1 diabetes were treated with the same highly purified bovine isophane insulin twice daily for 6 months (Starter group). Their insulin antibody levels rose from a geometric mean of 1.9 to 8.2 micrograms/l in contrast to values of 1.4 rising to 16.3 micrograms/l in an age and sex matched historical control group treated from diagnosis only with twice daily conventional bovine isophane insulin. Lipoatrophy at injection sites developed in three (9%) in the Starter group treated with highly purified bovine isophane compared to 7 (22%) of those on conventional bovine isophane. Insulin dose and diabetic control did not differ between the groups. Starter and Switch groups were subsequently treated with semi-synthetic human isophane insulin for 6 months during which insulin antibody levels fell significantly from a geometric mean of 8.5 to 4.4 micrograms/l (p less than 0.001). We conclude that bovine insulin purified to less than 1 ppm proinsulin is significantly less immunogenic than its conventional proinsulin contaminated counterpart but even at this level of purity is still more immunogenic than human insulin of equivalent purity.
Patients with active Hodgkin's disease (HD) often demonstrate an impaired T-cell proliferative response to phytohemagglutinin (PHA). The present study examined if interleukin regulation of the PHA response was defective in HD. The Hodgkin's PHA response was impaired at all concentrations of PHA utilized. Indomethacin increased the proliferative response but did not bring it to control levels. Stimulation of the cells with both PHA and irradiated Ia+ B cells normalized proliferation despite identical PGE2 concentrations as in the PHA alone cultures. Hodgkin's monocytes produced normal amounts of interleukin 1 (IL-1). Interleukin 2 (IL-2) production by Hodgkin's T cells was decreased in the PHA stimulated cultures, but was normal in the PHA and Ia+ cell stimulated cultures. In response to PHA stimulation alone, Hodgkin's T cells expressed less IL-2 receptor than control cells. The data suggest the diminished PHA response in HD is due to impaired IL-2 production resulting in diminished IL-2 receptor expression. However, when an Ia+ cell source is added to PHA as an additional stimulator, both TCGF production and proliferation are normalized. Monocytes serve to modulate the magnitude of the PHA response through production of both interleukin 1 and PGE2. However, in the presence of sufficient IL-2 production the influence of monocytes is minimized.
A rise in blood glucose concentration at the end of the night, and consequent morning hyperglycaemia, are well recognized events in some diabetic patients. In 94 patients on twice daily insulin injections we have examined the prevalence and extent of morning hyperglycaemia, and its relation to control, insulin therapy, and insulin antibody levels. Blood glucose reached the highest level of the day before or after breakfast in 83% of patients, and in 50% this value was 2 mmol/l greater than any other time of day. Patients with higher fasting concentrations did not have worse blood glucose control over the rest of the day. No correlation was found between fasting blood glucose concentrations and the evening dose of intermediate acting insulin or the level of insulin antibodies. No consistent change in fasting blood glucose concentrations occurred with changes in antibody levels in patients switched between pork and beef insulin. Morning hyperglycaemia was as common with both insulin species. Pre- and post-breakfast hyperglycaemia is common and significant in insulin-treated diabetic patients. It is not directly related to diabetic control at other times of the day, and is independent of insulin species and insulin antibody levels.
We have evaluated the clinical and immunogenetic features of 100 consecutive patients presenting to an adult diabetic clinic who were judged clinically to need insulin therapy but were not sufficiently ill to be admitted to hospital. Over this same period 15 newly diagnosed patients (aged 13-70 years) were started on insulin as in-patients of whom ten were in ketoacidosis. The 100 out-patients, aged 11-75 years at the time of starting insulin, were followed for at least a year. Fifty-six had islet cell antibodies and/or were heterozygous for HLA DR3 and DR4 (Group A) whereas 44 had neither of these markers (Group B). Islet cell antibodies and/or DR3, DR4 heterozygosity were most common in the 70 patients diagnosed below the age of 40 years but were also found in older patients. Patients in Group A were significantly younger at diagnosis (29 vs. 43 years), had a shorter duration of symptoms (17 vs. 61 weeks), were more likely to have ketonuria, and had a lower random C-peptide level at diagnosis (0.2 vs. 0.31 nmol/l). The two groups could not be distinguished by weight, haemogloblin A1 or blood glucose at diagnosis or by diabetic control or insulin dose after one year. The National Diabetes Data Group (NDDG) definition of insulin dependence stresses the importance of HLA types and islet cell antibodies although we found their prevalence to be low in the 30 patients diagnosed over 40 years who clinically were indistinguishable from the younger patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Proliferation of normal human T cells in vitro requires activation of resting T cells by lectin or antigen. This stimulation initiates a series of events which includes elaboration of T cell growth factor (TCGF), expression of TCGF receptors, and, ultimately, cellular proliferation. We sought to determine if TCGF was required for expression of the TCGF receptor in phytohemagglutinin (PHA)-stimulated normal human T cells. Utilizing dexamethasone (DEX), a known inhibitor of TCGF production, reductions in T cell proliferation, TCGF production, and TCGF receptor expression, as measured by TCGF adsorption and Tac acquisition, were demonstrated after PHA stimulation. When exogenous partially purified TCGF was added to DEX-containing cultures, the DEX inhibition of proliferation and TCGF receptor expression was completely reversed. These experiments were reproduced utilizing both highly purified TCGF from the Jurkat cell line and purified TCGF synthesized by bacteria from cloned TCGF DNA. Short-term experiments showed TCGF to be capable of restoring Tac antigen expression after DEX inhibition in the absence of cellular proliferation. These results indicate that TCGF is required for optimal expression of Tac antigen-associated TCGF receptors in PHA-activated T cells.
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Two patients with myelomatosis leading to acute renal failure were found at autopsy to have extensive crystalline deposits of paraprotein within the capsular space of the glomeruli, renal tubules and renal blood vessels. In one case, crystalline deposits in the renal arteries had caused infarction of both kidneys. Both patients had extensive paraprotein deposits in the heart and in other tissues, leading to myocardial infarction in one case. This patient also had extensive pulmonary deposits of paraprotein without a local plasma cell infiltrate, an appearance which has not been described before. Crystalline deposition does not appear to be specifically associated with a single class of paraprotein. This type of disease, affecting many organs, may be more common than has generally been appreciated and should be considered as a cause of otherwise unexplained organ failure in patients with myelomatosis.
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