Allergic reactions to carboplatin.
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Adult↗
Biomedical subjects
D Simmons
Publications and source records attributed to D Simmons.
Prevalence of diabetes in different regional and religious south Asian communities in Coventry.
The prevalence of Type 2 (non-insulin-dependent) diabetes in different South Asian (Asian) communities was compared during the Coventry Diabetes Study, a cross-sectional house to house screening programme for diabetes. Screening was by capillary whole blood glucose measurement with oral glucose tolerance tests when concentrations were greater than or equal to 6.0 mmol l-1 within 2 h of a meal or greater than or equal to 5.0 mmol l-1 2 h or more after a meal and a random 10% of others. Of the 4395 resident Asians, 94% were represented by five communities: Punjabi Sikhs, Punjabi Hindus, Gujerati Moslems, Gujerati Hindus, and Pakistani Moslems. Response to screening was 77-89% and to glucose tolerance test was 59-79%. Differences in anthropometry, socioeconomic circumstances, and migratory patterns were found, but all groups had a higher prevalence of Type 2 diabetes than Europeans. Gujerati Moslems had the highest age-adjusted prevalence (per 1000) of Type 2 diabetes (males: 160 (95% CI 107-228), females: 204 (95% CI 144-283)) when compared with the other Asian groups (males: Punjabi Sikhs 89(72-110), Pakistani Moslems 91(67-120), Gujerati Hindus 84(57-120), Punjabi Hindu 113(74-171); females: Punjabi Sikhs 75(60-94), Pakistani Moslems 103(78-133), Gujerati Hindus 88(62-122), Punjabi Hindu 116(77-174)). That all the Asian groups had a high prevalence of diabetes, in spite of their known dietary, cultural, and socioeconomic differences, suggests that the Asian predisposition to Type 2 diabetes is inherited although environmental factors may be necessary for this to be expressed.
Adult↗
Parity, ethnic group and the prevalence of type 2 diabetes: the Coventry Diabetes Study.
The prevalence of Type 2 (non-insulin-dependent diabetes) in relation to parity was compared among South Asian (Asian) and European women during a cross-sectional house-to-house screening programme for diabetes in Foleshill, Coventry, UK. The parity of female residents was ascertained in 8 of the 12 areas visited. These areas contained 2096 European (68 with diabetes diagnosed) and 1148 Asian women (95 with diabetes diagnosed). Crude prevalence of Type 2 diabetes was 3.2% and 14.7% in Europeans aged 30-64 years and > or = 65 years, respectively, and 10.9% and 36.5% in similarly aged Asians, respectively. In those aged 30-64 years, the age and body mass index adjusted prevalence of Type 2 diabetes was highest among nulliparous (Europeans 4.4%, Asians 16.3%) and grand multiparous (parity > or = 5: Europeans 6.3%, Asians 16.5%) women when compared with women who had had 1 or 2 deliveries (Europeans 0.9%, Asians 3.3%, p < 0.001, both ethnic groups). However, parity had no effect among women aged > or = 65 years.
Adult↗
Diabetes self help facilitated by local diabetes research: the Coventry Asian Diabetes Support Group.
Diabetic South Asians know less about the nature of diabetes than Europeans. In view of the difficulties in communicating with diabetic South Asians in a clinical environment, a 'self help group' was established. The group was initially resourced by the Coventry Diabetes Study, became independent after 2 years and has met monthly for 4 years. Meetings are led and organized by local diabetic South Asians and include invited speakers and discussions. All meetings are held in one of the South Asian languages, particularly Punjabi. Attendance has ranged from 15 to 50, almost exclusively from the surveyed diabetic population of one electoral ward. Those with a high glycated haemoglobin (HbA1 > 9.5%) were assessed 12 months after invitation to the group, 44% (22/51) of whom attended at least twice. Those living over 1 mile from the meeting place and those speaking a minority language were least likely to attend. Those who attended the group had a greater drop in HbA1 and increase in 'knowledge score' than those not attending (both p < 0.01). The continued existence of the group illustrates the ability of local health workers to facilitate and empower local communities to become more responsible for their own health.
Adolescent↗
Abnormal myoinositol influx in human leucocytes in diabetes but not specifically in diabetic neuropathy.
Abnormal myoinositol metabolism has been implicated as a contributor to the development of diabetic neuropathy. Furthermore, in vitro glucose inhibits animal and human myoinositol transporters. To investigate whether myoinositol transport is abnormal in diabetic subjects with and without neuropathy, we used a triple-isotope technique to measure [14C]myoinositol uptake in leucocytes from 23 insulin-dependent diabetic subjects and 13 matched nondiabetic subjects. All subjects with diabetes underwent neurophysiological studies, and subjects without neuropathy were compared with those with various degrees of neuropathy. The relationship between glycemia and flux was also studied. Diabetic subjects had similar intracellular and plasma myoinositol concentrations but had higher rates of uptake of myoinositol over the extracellular concentrations of myoinositol studied. Although the derived Km, Vmax, and passive components were not significantly different, the Vmax:Km ratio was significantly higher in diabetic subjects compared with nondiabetic subjects (0.25 [0.17-0.32] vs. 0.16 [0.13-0.19], respectively (P = 0.006). In diabetic subjects, the rate of myoinositol uptake correlated with HbA1c, particularly at 3 microM extracellular myoinositol where active uptake was a high proportion of the total influx (P less than 0.005). No difference in myoinositol uptake was found among diabetic subjects with various degrees of neuropathy. We conclude that although myoinositol transport is abnormal in diabetes, it is not specifically abnormal in diabetic neuropathy. Prolonged hyperglycemia is associated with higher myoinositol flux.
Biological Transport↗
Time to abolish the five hour glucose tolerance test?
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Adult↗
Serological response to measles revaccination in a highly immunized military dependent adolescent population.
In the spring of 1986, there was a measles outbreak in the city of El Paso, Texas, with 92 cases reported to the City-County Health Department. Of those 92 cases, 31 (32%) occurred within a public high school's student population of 2524. A mass measles vaccination program was undertaken at that high school in order to limit the outbreak. The student enrollment included a military dependent population of 368 students. Despite documented histories of prior measles immunizations in this military dependent subgroup, three individuals contracted the disease. Since this subgroup of students represented a highly immunized adolescent population, it was of interest to serologically determine their immune status prior to and following reimmunization with the expectation that such a study would provide information relating to the level of "protective" immunity. Prevaccination and postvaccination sera were obtained from 95 students. Results of measuring anti-measles antibody activity by ELISA indicate that 13 (14%) students responded to revaccination and experienced a fourfold or greater rise in IgG antibody levels. There were no detectable IgM responses. All of the students who responded to revaccination produced an anamnestic response (IgG boost only). Since most of these individuals had received first immunizations at 15 months of age or older, these findings suggest that secondary vaccine failure (waning immunity) was responsible for the putative "lowered" immunity in these individuals, instead of primary vaccine failure (maternal antibody suppression). These findings support current recommendations for measles booster revaccination of school-age children and adolescents.
Adolescent↗
The Coventry Diabetes Study: prevalence of diabetes and impaired glucose tolerance in Europids and Asians.
The Coventry Diabetes Study compared the prevalence of diabetes and impaired glucose tolerance in adult Asians and Europids in relation to age, sex and body mass index. The study involved a cross-sectional house to house screening for diabetes in the electoral ward of Foleshill, Coventry, a traditional area for migration into the city. Subjects with a high blood glucose and 10 per cent of others were referred for a 75 g oral glucose tolerance test. Of the 10,304 adult residents aged 20 years or above, 3529 (64 per cent) of 5508 Europids and 3692 (84 per cent) of 4395 Asians were either screened for diabetes or already diabetic and 719 (65 per cent) of 1114 Europids and 780 (72 per cent) of 1084 Asians invited to glucose tolerance test attended. Although the prevalence of insulin-dependent diabetes was similar, the age-adjusted prevalence of non-insulin-dependent diabetes was 3.2 per cent (95 per cent confidence interval (CI): 2.6-4.0) and 4.7 per cent (CI per cent 4.0-5.5) in Europid males and females but 12.4 per cent (CI 11.0-13.8) and 11.2 CI per cent (10.0-12.5) in Asian males and females giving prevalence ratios of 3.9 per cent (3.1-5.0) in males and 2.4 per cent (2.0-2.9) in females. These differences were not due to differences in body mass index. The prevalence of impaired glucose tolerance was also higher in Asians aged below 60 years, and in 65 per cent of Europids and 40 per cent of Asians non-insulin-dependent diabetes was previously undiagnosed. The non-insulin-dependent diabetes/impaired glucose tolerance ratio was significantly higher in Asians than Europids. Non-insulin-dependent diabetes in Asians differs from that in Europids. Besides the higher overall prevalence, there is a greater proportion of males, a lower proportion undiagnosed disease, a younger age at diagnosis and a greater proportion of abnormal glucose tolerance that is due to non-insulin-dependent diabetes.
Adult↗
Monoclonal antibody-defined epitope map of expressed rubella virus protein domains.
An expanded library of murine monoclonal antibodies (MAbs) was generated by infecting BALB/C mice with the Therien strain of rubella virus (RV) and selecting secreting hybrids by enzyme-linked immunosorbent assay (ELISA) using purified virion targets. A panel of plasmids containing specified RV cDNA fragments was also constructed by using a variety of strategies with pGE374- and pGE374-derived expression vectors. Hybrid RecA-RV-beta-galactosidase (LacZ)- or RecA-RV-truncated LacZ-containing proteins collectively representing the entire open reading frame of the structural proteins of RV were overexpressed in Escherichia coli. Bacterial lysates were then probed by ELISA with selected MAbs and by immunoblot following separation by electrophoresis under denaturing conditions. With this approach, MAbs that appeared to react with linear determinants defined epitopes localized within the following domains: MAbs C-1, C-2, and C-8 bind epitopes within the predicted amino-terminal 21 amino acids of the capsid region C9 to C29; MAb C-9 binds to a domain bounded by C64 and C97; MAbs E2-1 through E2-6 bind to the E2 glycoprotein backbone region from E2(1) to E2(115); MAbs E1-18 and E1-20 bind to the E1 glycoprotein region from E1(202) to E1(283). MAb E1-18 neutralizes RV infectivity; MAb E1-20 neutralizes infectivity and modestly inhibits hemagglutination. Analyses with selected synthetic peptides have confirmed several of the molecular domains deduced with the expressed proteins. These plasmid constructions and peptides have proven useful in beginning to unravel the molecular organization of several antigenic sites of this human pathogen.
Animals↗
Use of an impedance meter for measuring airways responsiveness to histamine.
We compared spirometry (FEV1) and airway impedance (z) in the assessment of airway responsiveness to histamine. Airway impedance was measured by the oscillator technique during quiet breathing; both measurements were made twice after each increment of histamine during the challenge. Percentage change in impedance was related to percentage change in FEV1 according to: -delta z = 1.09-2.66 (delta FEV1), r = -0.73, p less than 0.01, ie, impedance increased on average 2.7 times as much as FEV1 fell. The cut-off point for the standard test is the histamine concentration giving a 20 percent fall of FEV1 (PC20(FEV1)). The corresponding cut-off value chosen for impedance was a 30 percent increase (PC30(z)). (PC30(z)) = 0.74 (PC20(FEV1))-0.48, rs = 0.88, where rs is the Spearman rank correlation coefficient. Thus, impedance is a more sensitive index than FEV1 because a smaller dose of histamine gave a diagnostic result. Impedance is a practical alternative to FEV1, being less arduous for the patient and requiring little cooperation.
Adult↗
Effect of protein kinase C modulators on the leucocyte Na+/H+ antiport in type 1 (insulin-dependent) diabetic subjects with albuminuria.
It is uncertain why only one third of Type 1 (insulin-dependent) diabetic patients develop nephropathy. One suggestion is the inheritance of a predisposition to essential hypertension. We have previously found elevated Na+/H+ antiport activity and a raised intracellular pH in leucocytes from hypertensive and Type 1 diabetic subjects with albuminuria using a novel double ionophore fluorimetric technique. These changes are not found in Type 1 diabetic subjects without albuminuria. We wished to test the effect of a protein kinase C inhibitor staurosporine (100 nmol/l) on the elevated antiport activity, and the degree of stimulation achieved by exogenous diacyl glycerol. Raised leucocyte Na+/H+ antiport activity of Type 1 diabetic subjects with albuminuria (73.8 +/- 17.2 mmol.l-1.min-1) was restored to normal levels with staurosporine (54.9 +/- 17.9 mmol.l-1.min-1, p less than 0.001). The leucocyte Na+/H+ antiport activity of diabetic subjects without albuminuria fell significantly also with staurosporine but to a lesser extent (57.3 +/- 11.6 to 50.0 +/- 12.8 mmol/l, p less than 0.003). In contrast, leucocytes from normal control subjects showed no change in antiport activity with staurosporine (54.3 +/- 8.5 to 52.6 +/- 10.4 mmol.l-1.min-1). Dioctanoyl glycerol stimulated the leucocyte Na+/H+ antiport in normal subjects and diabetic patients without albuminuria, with significantly less stimulation in diabetic patients with albuminuria. We conclude that reversal by staurosporine of the elevated Na+/H+ antiport activity in Type 1 diabetic subjects with albuminuria could indicate a role for protein kinase C in activating the antiport. This hypothesis is supported by the reduced stimulation of the antiport by dioctanoyl glycerol in this group of patients.
Albuminuria↗
Leucocyte Na+/H+ antiport activity in type 1 (insulin-dependent) diabetic patients with nephropathy.
The development of proteinuria in Type 1 (insulin-dependent) diabetic patients may depend on predisposition to essential hypertension in addition to poor glycaemic control. Previous work has shown increased leucocyte Na+/H+ antiport activity in essential hypertension and increased erythrocyte Li+/Na+ exchange in Type 1 diabetic patients with proteinuria. To test whether susceptibility to nephropathy in Type 1 diabetes was linked to abnormalities of leucocyte Na+/H+ antiport activity, we measured the intracellular pH and kinetics of the Na+/H+ antiport in 19 Type 1 diabetic subjects with, and 15 diabetic subjects without albuminuria and compared them to 25 matched normal control subjects. Intracellular pH (mean +/- SD 7.59 +/- 0.14) and maximal transport capacity of the antiport (Vmax 87.7 +/- 24.9 mmol.1-1.min-1) were higher in diabetic subjects with albuminuria compared to normotensive control subjects (pH 7.44 +/- 0.09; Vmax 55.6 +/- 10.3 mmol.l-1.min-1; p less than 0.001 for both), similar to the defect described in essential hypertension. These differences were not seen in diabetic subjects with normal urinary albumin/creatinine ratios (pH 7.46 +/- 0.09; Vmax 61.0 +/- 13.6 mmol.l-1.min-1). Buffering characteristics of the leucocytes at different pH in the Type 1 diabetic subjects with albuminuria differed from normal control subjects and diabetic subjects with normal urinary albumin/creatinine ratios. We conclude that increased leucocyte Na+/H+ antiport activity, a known marker of essential hypertension, is usually associated with nephropathy in Type 1 diabetes.
Albuminuria↗
Leukocyte isotopically exchangeable intracellular sodium fractions in lean and overweight hypertensives.
Leukocyte intracellular sodium, as measured by flame photometry, is increased in essential hypertension, especially when associated with a body mass index greater than 27 kg.m-2. A triple isotope method for measuring the isotopically exchangeable pool of intracellular sodium was used to assess if this pool was increased in hypertension. No significant differences in the isotopically exchangeable intracellular sodium concentration were found between lean and overweight hypertensives compared with normotensive controls. Lean hypertensives with systolic blood pressures below the median had significantly lower exchangeable intracellular sodium concentrations than lean normotensives, whereas those with systolic blood pressures above the median had raised exchangeable intracellular sodium concentrations. The obese hypertensives did not show this trend. The exchangeable intracellular sodium concentration was correlated to systolic (r = .53, P less than .001) and diastolic (r = 0.39, P less than .01) blood pressure in hypertensives. We conclude that the increase in total cellular sodium content (as measured by flame photometry) in hypertensives described in previous studies is not associated with any increase in the isotopically exchangeable pool of intracellular Na+, except in those lean hypertensives with systolic blood pressures above the median. By implication, there may be an increased slowly exchangeable pool of intracellular Na+ in leukocytes from most hypertensives.
Adult↗
myo-inositol influx into human leucocytes: methods of measurement and the effect of glucose.
1. Low intracellular concentrations of myo-inositol in diabetic cells may contribute to the development of tissue damage. The cause of these low levels is unknown, but inhibition of a putative myo-inositol transporter by high concentrations of glucose has been proposed. We have developed a triple-isotope method for estimating myo-inositol influx into human leucocytes and so investigated both the kinetics of this uptake in normal volunteers and the effect of glucose upon it. 2. Uptake was composed of a passive component with a rate constant of 2.4 +/- 0.3 X 10(-2) min-1 and a saturable component with a Km of 61 +/- 23 mumol/l and Vmax of 11.3 +/- 4.5 X 10(-4) mmol min-1 l-1. Ouabain and low extracellular concentrations of sodium partly inhibited influx. Uptake was predominantly into the cytosolic fraction of the cell with 12% entering the membrane-associated fraction at both 5 and 10 min. 3. myo-Inositol influx was significantly inhibited by both D- and L-glucose but not by sucrose. Neither cytochalasin B nor ethyl isopropyl amiloride significantly inhibited uptake. 4. It is concluded that a myo-inositol transporter exists in human leucocytes which is similar to that found in other species and tissues. Our technique allows myo-inositol influx in diabetic subjects to be related to varying glycaemic control and tissue damage.
Adult↗
Chromosome 1 localization of the gene for CD34, a surface antigen of human stem cells.
CD34 is a surface antigen expressed on normal human hematopoietic stem cells, as well as on the blast cells of many patients with both lymphocytic and myelocytic leukemias. By Southern blot analysis of DNA from a panel of human x mouse somatic cell hybrids using a CD34 cDNA probe, we demonstrate that the gene for CD34 is located on human chromosome 1 in the 1q12----qter region.
Animals↗
Cellular sodium influx is low in type 1 (insulin dependent) diabetes.
Leucocyte sodium influx was studied in 29 type 1 (insulin dependent) diabetic subjects and compared to 24 non diabetic controls matched for age, body mass index and blood pressure. Total sodium influx from a low external concentration ((Na+) = 10 mmol/l) was reduced in type 1 diabetes (0.23 vs 0.31 mmol/l/min, p less than 0.05) as was amiloride insensitive sodium influx (0.09 vs 0.13 mmol/l/min, p less than 0.01). No difference was found in amiloride sensitive flux. No ionic flux was correlated with plasma glucose or insulin concentrations or with HbA1 levels. Intracellular sodium accumulation in type 1 diabetes is not due to an increase in total sodium influx, as judged from an external concentration of 10 mmol/l.
Adult↗
Prevalence of diabetes in a predominantly Asian community: preliminary findings of the Coventry diabetes study.
To assess the prevalence of both diagnosed and undiagnosed diabetes mellitus in an area of predominantly Asian population the Coventry diabetes study is carrying out house to house screening for diabetes in people aged 20 and over in Foleshill, Coventry. In the first five of 12 areas to be studied 2130 of 2283 Asian (93.3%) and 1242 of 1710 white subjects (72.6%) aged 20-79 agreed to be screened. The prevalence of diabetes adjusted to 1987 demographic estimates was 11.2% in Asian men and 8.9% in Asian women whereas it was 2.8% in white men and 4.3% in white women. The excess of diabetes in Asian subjects was predominantly of non-insulin-dependent diabetes, and no significant differences in body mass were found to account for the higher prevalence. Diabetes had not been diagnosed previously in at least 26% of the white and 30% of the Asian diabetics screened, and it is estimated that in this community the condition remains undiagnosed in 42% of white and 40% of Asian diabetics.
Adult↗
Limitations of capillary plasma immunoreactive insulin assay as an epidemiological tool.
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Capillaries↗