Biomedical subjects
Publications and source records attributed to G Ward.
Increases in both the cost of providing quality diabetes care and in the number of people developing diabetes have led to a search for more cost effective models of care. This paper outlines a shared care scheme that has benefits for the patient, the outpatient clinic and the general practitioner.
Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To compare the magnitude and reproducibility of the FPIR measured during two different IVGTT protocols in nondiabetic subjects. RESEARCH DESIGN AND METHODS: Nine control subjects each had two pairs of IVGTTs with either a 4-min infusion of 0.5 g/kg glucose or a 1-min infusion of 0.3 g/kg glucose. Blood glucose and serum insulin were measured before and 1, 2, 3, 5, and 10 min after completion of the glucose infusion. The FPIR was measured with either 1 + 3-, 2 + 3 + 5-, or 1 + 3 + 5-min serum insulins, areas under the insulin curve (0-5 or 0-10 min), or the ratio of serum insulin to blood glucose area. RESULTS: The FPIR was higher in eight of nine subjects with the short-infusion test, but the within-subject variation of the two methods was identical. Reproducibility was not significantly improved with an integrated insulin area or insulin-to-glucose ratio measurement. CONCLUSIONS: Reproducibility of the FPIR measured during IVGTT is not significantly affected by the duration of the glucose infusion. However, the magnitude of the difference in FPIR observed between the two protocols highlights the need for standardization of the methodology if the IVGTT is to be used in studies of the preclinical stage of IDDM.
A 6-year-old girl with Carpenter's syndrome is reported who, in spite of a considerably distorted and small calvarium at birth, has normal mental development. Cranio-facial surgery was carried out in infancy, but its role in respect to mental development is difficult to assess since unoperated patients with normal intelligence and Carpenter's syndrome have been widely reported. Nevertheless, early cranio-facial surgery is recommended for cosmetic reasons.
STUDY OBJECTIVE: To determine the feasibility of managing patients with acute pyelonephritis as outpatients after initial treatment with IV antibiotics in an emergency department observation unit. DESIGN: Prospective and uncontrolled. SETTING: ED observation unit. TYPE OF PARTICIPANTS: Nonpregnant female patients 14 years old or older without immunocompromise or serious underlying disease and no evidence of septic shock. INTERVENTIONS: All patients received two IV doses of trimethoprim/sulfamethoxazole at a 12-hour dosing interval and promethazine and acetaminophen as needed for nausea and fever, respectively. Baseline laboratory data, urinalysis, and urine and blood cultures were obtained. MEASUREMENTS AND MAIN RESULTS: Patients were observed for signs of septic shock, nausea, vomiting, and the ability to tolerate an oral intake. At the end of the observation period, 43 of 44 patients were discharged on oral trimethoprim/sulfamethoxazole. One additional patient who was doing well clinically was recalled and admitted because of a positive blood culture. CONCLUSION: Patients with acute pyelonephritis, despite significant fever or nausea and vomiting, can be treated effectively as outpatients after a brief period of observation and IV antibiotics.
OBJECTIVE: We wished to assess the contributions of insulin secretion, insulin sensitivity and glucose-mediated glucose disposal to glucose tolerance in subjects exposed to chronic glucocorticoid excess. DESIGN: Patients with Cushing's disease were subjected to a frequently sampled intravenous glucose tolerance test before and at least 3 months after curative surgery and compared to a control group. PATIENTS: Seven patients with clinical and biochemically proven pituitary dependent Cushing's disease and 10 healthy control subjects were studied. MEASUREMENTS: Paired glucose and insulin plasma profiles were analysed by the Minimal Model method of Bergman, which provided simultaneous estimates of the glucose decay rate, insulin secretion, insulin sensitivity and glucose-mediated and non-insulin-mediated glucose disposal. Data were evaluated by non-parametric statistical analysis and reported as median and interquartile ranges. RESULTS: Basal glucose, insulin, C-peptide and glucagon levels were significantly raised preoperatively and fell towards normal post-operatively. Glucose tolerance assessed as glucose decay rate was reduced significantly preoperatively (pre: 1.3 (0.8-2.0) vs post: 1.6 (1.5-2.6) per min x 10(2), P less than 0.05). First phase insulin release was similar in the Cushing's disease and control subjects. In contrast, second phase insulin release was significantly greater preoperatively and remained high post-operatively compared to control subjects (pre: 18.8 (16.7-23.6) vs post: 16.7 (8.5-18.8) vs control 11.1 (4.5-15.4) mU/g/min2 x 10(-2), P less than 0.002). Median insulin sensitivity was reduced by 60% preoperatively in the Cushing's disease subjects compared to the post-operative Cushing's disease and control subjects (pre: 2.1 (1.3-4.2) vs post: 5.0 (3.2-7.3) vs control 5.1 (2.2-7.2) per min/mU/l x 10(4)). Median glucose-mediated glucose disposal was reduced by 40% in the pre and post-operative Cushing's disease subjects compared to the control group (pre: 1.1 (0.6-2.1) vs post: 1.1 (0.6-2.1) vs control 1.9 (1.4-2.6) per min x 10(2)), but this was not statistically significant. However, non-insulin-mediated glucose disposal was significantly reduced in the preoperative Cushing's disease subjects (pre: 0.55 (0.08-1.59) vs control 1.43 (0.94-2.27) per min x 10(2), P less than 0.05). In the Cushing's disease subjects, glucose tolerance correlated with both insulin sensitivity (rs = 0.84, P less than 0.01) and non-insulin-mediated glucose disposal (rs = 0.56, P less than 0.05). The fractional clearance rate of insulin was unaltered by Cushing's disease. CONCLUSIONS: Cushing's disease subjects are characterized by impaired glucose tolerance due to both reduced insulin sensitivity and non-insulin-mediated glucose disposal, in the presence of enhanced insulin secretion.
In 1983, The Methodist Hospital of Houston, Texas--the largest private nonprofit acute care hospital in the United States--revised its quality assurance (QA) program to integrate Joint Commission standards with the mission of the hospital. The revised QA program includes the medical staff, hospital departments, management, and a Caring Through Service Task Force, which evaluates services from the patient's perspective.
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Six prepubertal children with chronic renal failure (group 1), six prepubertal children with renal transplants (group 2), and six pubertal children with renal transplants (group 3) who were short (mean height SD score, -3.2, range -4.5 to -1.6) and growing poorly (mean (range) growth velocity (cm/year) over the year before treatment: group 1, 4.8 (3.5-5.8), group 2, 2.3 (0.9-4.7), and group 3, 3.2 (0.5-6.5] were treated with recombinant human growth hormone 30 units/m2/week in daily doses for a median of 0.98 years (range 0.25-0.99). Mean (range) growth velocity over the treatment period increased significantly in all groups (group 1, 10.7 (8.8-12.3), group 2, 6.1 (2.7-10.8), and group 3, 6.0 (4.6-6.8]. There was, however, no improvement in height SD score for bone age in any group. The renal function of two children deteriorated after starting treatment with growth hormone, but it was not possible to say whether the growth hormone was responsible for this. The long term effects of treatment and its influence on final height are not yet known.
In order to evaluate simultaneously in thyrotoxic subjects the relative contributions of insulin secretion, insulin-sensitivity (SI) and glucose-mediated (SG) glucose disposal to overall glucose tolerance, seven non-obese patients with thyrotoxicosis were studied by the minimal model analysis of the frequently sampled intravenous glucose tolerance test, before and greater than 1 month after being rendered euthyroid, and compared with eight healthy control subjects. Basal glucose, C-peptide and glucagon levels were similar in all groups but, in the toxic and euthyroid states, basal insulin levels were significantly elevated compared to the control group (11.2 +/- 2.0 and 7.9 +/- 1.1 vs 5.1 +/- 0.6 microU/ml, mean +/- SE, P less than 0.02). FFA levels were raised in the thyrotoxic subjects prior to treatment (0.95 +/- 0.11 vs 0.68 +/- 0.08 and 0.54 +/- 0.08 mmol/l, P less than 0.02). Glucose tolerance (Kg) was reduced in the thyrotoxic subjects compared to the euthyroid state (1.16 +/- 0.12 vs 1.44 +/- 0.13 per min, P less than 0.025) and control group (1.44 +/- 1.0 per min, 0.05 less than P less than 0.1). First phase (phi 1) and second phase (phi 2) insulin release were both significantly elevated in the thyrotoxic and euthyroid states compared to the control group (phi 1 7.10 +/- 1.88 and 5.29 +/- 1.03 vs 1.72 +/- 0.17 microU/mg/min X 10(-2), P less than 0.01; phi 2 18.64 +/- 3.14 and 16.74 +/- 4.48 vs 9.23 +/- 0.74 microU/mg/min X 10(-2) respectively, P less than 0.02). SG was similar in all groups but SI was significantly reduced in the thyrotoxic subjects compared to the control group (2.24 +/- 0.62 vs 5.92 +/- 1.50/min/microU/ml X 10(4), P less than 0.02) and rose post-treatment in the euthyroid subjects (4.23 +/- 1.75/min/microU/ml X 10(4)). In the thyrotoxic subjects before and after treatment, log SI correlated negatively with basal FFA levels (r = -0.57, P less than 0.05) and with phi 2 (r = -0.58, P less than 0.05). The fractional clearance rate of insulin was unaltered by the thyrotoxic state. It is concluded that in thyrotoxicosis the impairment of Kg is due to reduced insulin sensitivity in the presence of enhanced insulin secretion, but glucose-mediated glucose disposal is unaltered by the toxic state.
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The safety and clinical efficacy of calcium carbonate therapy in children with chronic renal failure were assessed in 68 patients (average age 8.38 years) during a mean follow-up period of 19.9 months (range 1.2-49.4). Forty-seven episodes of hypercalcaemia occurred in 29 children (3.5 episodes per 100 patient-months). There were no significant differences in mean GFR or biochemical parameters between these patients at the start of calcium carbonate therapy and the group of children who never experienced hypercalcaemia. Good control of secondary hyperparathyroidism and a significant reduction in serum aluminum were achieved. Two of 23 hypercalcaemic patients showed nephrocalcinosis on ultrasonography. 99Tc pyrophosphate scanning failed to detect any other ectopic calcification. The incidence of hypercalcaemia increased significantly when the GFR was less than 15 ml/min per 1.73 m2 and was most frequent in children receiving dialysis (48 episodes per 100 patient-months). The decrease in GFR during therapy was significantly more in the hypercalcaemic group compared to the normocalcaemic group (P less than 0.01), despite no irreversible acute effects of hypercalcaemia being observed on the rate of decline of GFR. We believe that the reduced renal homeostatic reserve is a major factor predisposing to hypercalcaemia. Consequently calcium carbonate is safe to use in children with severe chronic renal failure with close biochemical monitoring; the benefits over aluminium phosphate binders far outweigh the risks of hypercalcaemia and ectopic calcification.
A postal questionnaire survey was conducted comparing the workload and remuneration of part-time women principals in group practices in the Northern and Oxford regions. Part time was defined as receiving less than a full profit share at parity. Of 501 women principals 308 (62%) responded of whom 146 (47%) were part-time. Respondents were asked to record aspects of workload over a four-week period for themselves and their full-time partner who did the most sessions within the practice. The results showed that although two-thirds of the part-timers had 50% or less of a full profit share, part-time principals overall did about 76% of the daytime clinical work (surgeries and home visits) done by their full-time partners, excluding specialized clinics. The lower the profit share the wider this discrepancy. Although 33% of the respondents did not out-of-hours work, the remainder did more than their profit share would indicate. Twenty per cent of the 116 principals with 40% or more of a full profit share and 57% of the 30 principals with less than 40% of a full profit share felt that their share was unfair. Lack of involvement in practice business and feeling that opinions did not carry equal weight were associated with feelings of unfairness.
This study was undertaken to clarify the issue of whether feedback regulation of pancreatic enzyme secretion occurs in humans. A naturally occurring inhibitor of trypsin and chymotrypsin, the Bowman-Birk inhibitor of soybeans, was used to reduce the activities of these enzymes normally secreted by the pancreas into the duodenum. Pure pancreatic juice was collected by endoscopic retrograde cannulation of the pancreatic duct in a protocol consisting of three periods: period 1 (15 min), collections of juice without return to the duodenum ("washout phase"); period 2 (35 min), intraduodenal infusion of juice to which buffered saline or heat-inactivated Bowman-Birk inhibitor had been added; and period 3 (55 min), intraduodenal infusion of juice in which greater than 90% of the trypsin and chymotrypsin activities had been abolished by treatment with the active inhibitor. Control experiments were included in which untreated juice was infused in period 3 as well as period 2. Enzyme analyses (trypsin, chymotrypsin, elastase, and amylase) of samples of juice collected at 5-min intervals revealed a twofold to threefold increase in the output and concentration of all four enzymes in period 3 compared with period 2. These results thus confirm the existence of feedback control in humans.
It is not known whether circulating norepinephrine (NE) has a direct hormonal influence on glucose disposal. This study examines whether moderate elevation of NE alters the disposal of an acute intravenous (IV) glucose load, as analysed by the minimal model of Bergman. Eight healthy normal subjects were infused with either 25 ng/kg/min NE (plasma NE 1,284 +/- 259 pg/mL) or normal saline (plasma NE 314 +/- 86 pg/mL), 30 minutes prior to and during an IV glucose tolerance test (GTT). There was a small but significant rise (P less than .05) in basal blood glucose levels during the initial 30-minute NE infusion which was accompanied by a 40% increase (0.39 +/- .02 to 0.59 +/- .07 nmol/L, P less than .01) in nonesterified fatty acid levels (NEFA). Insulin, C-peptide, and glucagon levels did not change. NE impaired the rate of acute glucose disposal (Kg 1.74 +/- 0.24 v 2.10 +/- 0.23 (min-1, P less than .05). Minimal model analysis revealed a corresponding 35% decrease in insulin sensitivity (SI 4.85 +/- 1.51 v 7.28 +/- 1.16 min-1 microU-1 mL-1 x 10(4), P less than .05) but no significant differences between glucose-mediated glucose disposal or pancreatic B-cell responsiveness. The glucose disposition index (si* phi2), a direct measure of an individual's overall insulin- mediated glucose disposal, was reduced by 70% in the NE-infussed subjects (si* phi2 69 +/-22 v 223 +/- 76 mg-1 ml-1 min-3 x 10(2), p< .05).(ABSTRACT TRUNCATED AT 250 WORDS)
We estimated the event rates for stroke and transient cerebral ischemic attacks in a prospective community-based epidemiologic study in a representative segment of the city of Perth, Western Australia, during a 10-month period in 1986. Of 349 persons with an initial diagnosis of stroke or transient ischemic attack, 154 had suffered a first stroke, 75 a recurrent stroke, and 47 a transient ischemic attack; the remaining 73 persons were thought not to have had an episode of acute cerebrovascular disease. Annual event rates for first stroke (age-standardized to the "world" population) were 120 per 100,000 for males and 56 per 100,000 for females. The crude case-fatality ratio at 28 days after the index event for first stroke was 23% and varied from 0% for lacunar infarction to 57% for subarachnoid hemorrhage.
One hundred and twenty-nine patients notified to the Perth Community Stroke Study in whom the final diagnosis was cerebrovascular disease were matched with controls of the same sex and 5-year age group drawn from the records of the usual general practitioner of each index case. The control subjects were interviewed and examined briefly at home, following the same protocol as that used for assessment of cases. The significant risk factors for cerebrovascular disease to emerge in the case-control comparison were previous stroke (estimated relative risk 6.6), signs of peripheral vascular disease (3.6) and current smoking (2.6). Being married (0.6) and history of migraine (0.4) were significant protective factors. There was no association between a history of hypertension and cerebrovascular disease in this series.
A community-based register of cases of acute cerebrovascular disease in a representative segment of the city of Perth, Western Australia, has been developed. Stroke attack rates, pathological diagnoses and site of care of the cases, as revealed by the register, are analysed.