20 THz broadband generation using semi-insulating GaAs interdigitated photoconductive antennas.

We demonstrate broadband (20 THz), high electric field, terahertz generation using large area interdigitated antennas fabricated on semi-insulating GaAs. The bandwidth is characterized as a function of incident pulse duration (15-35 fs) and pump energy (2-30 nJ). Broadband spectroscopy of PTFE is shown. Numerical Drude-Lorentz simulations of the generated THz pulses are performed as a function of the excitation pulse duration, showing good agreement with the experimental data.

Coherent nonlinear optical response of graphene.

We investigate the nonlinear optical properties of graphene flakes using four-wave mixing. The corresponding third-order optical susceptibility is found to be remarkably large and only weakly dependent on the wavelength in the near-infrared frequency range. The magnitude of the response is in good agreement with our calculations based on the nonlinear quantum response theory.

Evaluation of a local optometric diabetic retinopathy screening service.

AIMS: To determine the sensitivity and specificity for sight-threatening eye disease (STED) of the diabetic retinopathy screening scheme for Stockport during the period 1 April 2000 to 31 March 2001. METHODS: A random sample of screen-negative patients was recalled for further assessment by consultant ophthalmologists. Screen-positive patients, who were referred, were tracked through the hospital system to determine the outcome. RESULTS: In a 12-month period, 3510 individuals with diabetes were screened, which is 1.2% of the district population. Sensitivity for STED was 75.8%[95% confidence interval (CI) 49.3, 99.99] and specificity for STED was 99.0% (95% CI 98.6, 99.3). CONCLUSIONS: The current screening arrangements in Stockport are satisfactory in terms of sensitivity and specificity. Population coverage was 1.2% over 12 months and 1.5% over 15 months and needs to be improved. An integrated computerized register requires further development.

Community development theory. Planning a community nursing center.

The authors describe the use of community development theory to assess the need for a community-based, nurse-managed primary care clinic. A community development model provided the framework for citizen participation in identifying collective health needs of public housing residents. The model facilitated the following: 1) planning for delivery of culturally appropriate primary care services that respond to health needs perceived by community residents; 2) ensuring acceptability and use of services; and 3) empowering residents to take responsibility for their own health. This article focuses on the assessment phase of the model and meeting the perceived needs of community residents.

Women's self-efficacy and sexually transmitted disease preventive behaviors.

Knowledge of sexually transmitted disease (STD) prevention, perceived risk for STDs, and self-efficacy for STD prevention were investigated as predictors of behavioral risk for STDs in 308 female college students. Perceived risk and self-efficacy predicted 19% of behavioral risk for STD; knowledge was not a predictor. Self-efficacy was highest for communicating about STD prevention and lowest for refusing sexual intercourse. Interventions that enhance both women's self-efficacy to prevent STDs and accurate risk appraisal are likely to be more effective than those that emphasize only knowledge of prevention techniques.

Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion.

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of monomeric insulin analogues of different receptor affinity.

The effects of two monomeric insulin analogues of differing receptor affinities (human insulin = 100%) B9Asp-B27Glu-insulin (18%) and B10Asp-insulin (327%) were each compared with human insulin in two groups of 10 normal men when infused at equimolar low doses (1.0 and 2.0 pmol kg-1 min-1). The metabolic clearance rate under steady state conditions was highest for the analogue with the highest receptor affinity, 26.8 +/- 0.8 (+/- SE) vs 19.8 +/- 0.7 ml kg-1 min-1 for insulin (p less than 0.001), and lowest for the analogue with the lowest receptor affinity, 13.3 +/- 0.8 vs 25.1 +/- 2.0 ml kg-1 min-1 for insulin (p less than 0.001). The apparent plasma half-life was prolonged for the low affinity analogue compared with human insulin (12.6 +/- 0.6 vs 1.9 +/- 0.2 min, p less than 0.001), and significantly shorter for the higher affinity analogue (1.6 +/- 0.1 vs 3.1 +/- 0.4 min, p less than 0.05). The three insulins gave similar falls in blood glucose, non-esterified fatty acids, glycerol, and total ketone bodies over the infusion period. Thirty minutes after the end of the infusion, the rise in blood glucose for the low affinity analogue was significantly less than for human insulin (0.5 +/- 0.2 vs 0.9 +/- 0.1 mmol l-1, p less than 0.05). Despite different receptor affinities, these analogues have similar in vivo effects in normal men, but the time-course of their actions may differ when they are infused intravenously.

Basal intermediary metabolism in impaired glucose tolerance and morbid obesity.

The effects of impaired glucose tolerance and obesity, in isolation and in combination, on basal (postabsorptive) intermediary metabolism were examined in four groups of subjects (n = 10 for each) matched for age and gender: Group 1: Non-obese healthy controls with normal glucose tolerance (75 g); Group 2: Non-obese subjects with impaired glucose tolerance; Group 3: Morbidly obese subjects with normal glucose tolerance; Group 4: Morbidly obese subjects with impaired glucose tolerance. While there was no significant difference in fasting blood glucose concentrations between the four groups plasma immuno-reactive insulin concentrations were elevated (p < 0.01 or less) in the obese subjects relative to the non-obese subjects within each category of glucose tolerance. Basal immunoreactive insulin concentrations in non-obese subjects with impaired glucose tolerance were also elevated (p < 0.01) relative to the non-obese healthy controls. Concentrations of glycerol (p < 0.01), non-esterified fatty acids (p < 0.01), and total ketone bodies (p < 0.001) were significantly higher in the obese/normal glucose tolerance and obese/impaired glucose tolerance groups relative to their matched non-obese counterparts. Compared with the subjects with normal glucose tolerance, only lactate (p < 0.05) and pyruvate (p < 0.05) concentrations were elevated in the non-obese/impaired glucose tolerance and obese/impaired glucose tolerance groups, respectively. In conclusion, in addition to fasting hyperinsulinaemia the regulation of lipolysis and ketone body metabolism is abnormal in the basal state in morbid obesity. By contrast, despite normal fasting blood glucose concentrations, impaired glucose tolerance is associated with disturbances of other aspects of basal carbohydrate metabolism.

Metabolic effects of pharmacological adrenergic blockade in phaeochromocytoma.

Twelve-hour hormonal and metabolic profiles were performed in a 68-year-old woman with a benign adrenal phaeochromocytoma (a) prior to adrenergic blockade, (b) after the establishment of pharmacological alpha-blockade with phenoxybenzamine, (c) after combined alpha and beta-blockade with phenoxybenzamine and propranolol, and (d) after successful surgery and withdrawal of medication. Pretreatment, (a) vs (d), significant elevations (12-h mean +/- SD) were observed in the concentrations of noradrenaline (44.9 +/- 14.4 vs 2.3 +/- 0.7 nmol/l, P less than 0.01), glucose (6.9 +/- 1.9 vs 5.0 +/- 1.0 mmol/l, P less than 0.05), glycerol (0.22 +/- 0.02 vs 0.07 +/- 0.01 mmol/l, P less than 0.01), non-esterified fatty acids (0.71 +/- 0.28 vs 0.34 +/- 0.08 mmol/l, P less than 0.01), and total ketone bodies (0.08 +/- 0.03 vs 0.03 +/- 0.02 mmol/l, P less than 0.01). Alpha-blockade, (b) vs (a), was associated with an increase in noradrenaline levels (P less than 0.01) but not with any significant alterations in intermediary metabolite concentrations. Following the establishment of combined alpha and beta-blockade, (c) vs (b), plasma noradrenaline returned to its pretreatment level while the concentrations of glycerol, fatty acids and ketone bodies were normalized. A completely physiological 12-h blood glucose profile, however, was observed only post-operatively. No significant differences were observed in mean plasma insulin levels between the four studies. These results indicate impaired regulation of multiple aspects of carbohydrate, lipid and ketone body metabolism in our patient.(ABSTRACT TRUNCATED AT 250 WORDS)

The short-term effect of nicotinic acid on intermediary metabolism in insulin-dependent diabetes mellitus.

The short-term effect of the lipid lowering agent nicotinic acid on circulating concentrations of insulin, glucose, lactate, pyruvate, non-esterified fatty acids (NEFA), glycerol, total ketone bodies and triglycerides was examined in six insulin-dependent diabetic patients. On two occasions a week apart 24h metabolic profiles were performed. Three patients received nicotinic acid (800 mg/day) for 1 week prior to the first study and three patients between studies. Using this dose of nicotinic acid in patients with insulin-dependent diabetes no lipid lowering effect was demonstrated, nor did we observe an impairment of glycaemic control. During treatment with nicotinic acid circulating free insulin concentrations were higher and blood glucose concentrations were lower. Despite the higher insulin concentrations, circulating levels of NEFA, ketone bodies, and glycerol were all significantly elevated during treatment with nicotinic acid. These results suggest that any extrapolation of findings with regard to the use of nicotinic acid and its derivatives in non-insulin-dependent diabetes to insulin-dependent diabetes should be considered with caution.

Changing sex ratio in diabetic ketoacidosis.

An annual audit of diabetic ketoacidosis and hyperosmolar non-ketotic state was made in one hospital from 1971 to 1988. There were 846 episodes of ketoacidosis and 126 episodes of hyperosmolar state. A relative fall occurred in the number of episodes of ketoacidosis compared with hyperosmolar state over this time (p less than 0.05), and there was a change of female:male ratio for episodes of ketoacidosis occurring in established diabetes from 2.79 to 1.59 (p less than 0.01). In contrast the female:male ratio remained unchanged (mean 1.16) for episodes of hyperosmolar state and remained less than 1.0 for all episodes of ketoacidosis in previously undiagnosed diabetes mellitus. Among patients who suffered recurrent ketoacidosis there was a reduction in the number of episodes occurring in female patients and an increase in the number of episodes occurring in male patients in each successive 6-year period with consequent change in female:male ratio for this subgroup from 7.33 to 4.75 to 1.12 (p less than 0.001).

Intra-operative blood glucose and serum insulin concentrations in the surgical management of insulinoma.

The surgical management of insulinoma is frequently complicated by difficulty in pre- and intra-operative localization of the tumour. An early and reliable post-operative indicator of successful surgery would therefore be useful in the management of this condition. In a prospective, controlled study serial measurements of blood glucose and serum insulin concentrations were performed in 5 patients with insulinoma during surgical removal of the tumour. Results were compared with 5 patients, matched for age and body weight, undergoing abdominal surgery for non-malignant disease. Serum insulin (mean +/- s.e.m.) was significantly elevated in the insulinoma patients at the start of surgery (32.1 +/- 3.1 vs 6.1 +/- 2.2 mU/l; P less than 0.01). A significant fall (P less than 0.01) to levels comparable with the control patients (7.5 +/- 1.8 vs 10.0 +/- 3.3 mU/l) occurred following removal of the tumour. We conclude that serial intra-operative measurements of serum insulin concentration are technically simple to perform and provide useful retrospective corroboration of successful surgery in patients with insulinoma.

Xiaoke tea, a Chinese herbal treatment for diabetes mellitus.

Xiaoke tea, a traditional Chinese treatment for diabetes mellitus, lowered blood glucose concentrations in streptozotocin diabetic mice. To investigate Xiaoke clinically, a double-blind crossover study was undertaken in 12 non-insulin-treated diabetic patients. Xiaoke tea and ordinary tea (infusion of 2.72 g, 4 times daily) were consumed in random order for 4 weeks. A standard breakfast meal was taken before and after each treatment period. Xiaoke did not significantly affect glycosylated haemoglobin, basal or post-breakfast serum glucose and insulin concentrations, intermediary metabolite concentrations, triglyceride and cholesterol. No adverse side-effects of Xiaoke were evident.

Serum fructosamine in diabetic pregnancy.

Serum fructosamine was assessed in 41 previously diagnosed diabetic patients throughout pregnancy and compared with other standard measures of glycaemic control. Fructosamine was measured by a precise automated method using the reduction of nitro-blue tetrazolium at alkaline pH. Corrected serum fructosamine was calculated from serum fructosamine and serum protein concentrations in view of the falling protein concentrations during pregnancy. Serum fructosamine corrected for total serum protein was significantly lower at the end of pregnancy than at the initial visit. Clinic blood glucose, HbA1c and fructosamine corrected for serum albumin did not fall significantly. Fructosamine corrected for total protein concentration at all points through pregnancy showed positive correlations with birth weight ratio (r = 0.51-0.67). HbA1c did not show the same consistent pattern of results. The correlation of first and second trimester fructosamine values with birth weight ratio suggests that glucose control is a determinant of birth weight throughout pregnancy rather than just in the last trimester.

The effect of glucose and insulin infusion on the fall of ketone bodies during treatment of diabetic ketoacidosis.

During the treatment of diabetic ketoacidosis intravenous glucose is infused when blood glucose has fallen to around 14 mmol l-1. The use of hypertonic (10%) glucose has been recommended in order to hasten the clearance of blood ketone bodies. In a randomized controlled study 17 patients presenting with severe diabetic ketoacidosis were allocated to one of two regimens of intravenous glucose and insulin when blood glucose had fallen to less than 14 mmol l-1. Nine patients were given 5% glucose containing 10 U l-1 insulin and 8 patients received 10% glucose with 40 U l-1 insulin. Fluid was infused at a rate of 250 ml h-1 for 6 h. At the start of the infusions blood glucose had fallen from levels at presentation to 12.8 +/- 1.1 mmol l-1 (mean +/- SE) in the group which subsequently received the low infusion rate and to 13.7 +/- 0.9 mmol l-1 in the subsequent high infusion rate group. With glucose/insulin infusion blood glucose after 6 h was 11.5 +/- 0.9 mmol l-1 (low infusion rate group) and 15.7 +/- 1.3 mmol l-1 (high infusion rate group). This difference between groups at 6 h was significant (p less than 0.05). Over the 6 h of infusion the fall in blood total ketone bodies was significantly greater in the group receiving the higher rate of glucose/insulin infusion (7.34 +/- 0.57 vs 5.18 +/- 0.57 mmol l-1; p less than 0.05). Despite the greater fall in total ketone bodies in this group there was no difference in the improvement in capillary blood pH or bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic profiles in patients with insulinoma.

Twelve-hour metabolic profiles have been measured in six patients with insulinoma and results compared with normal subjects of similar age and weight. Fasting blood glucose was lower (mean +/- SEM 2.9 +/- 0.3 mmol/l vs 5.0 +/- 0.2 mmol/l) and plasma insulin higher (20.0 +/- 3.9 mU/l vs 7.2 +/- 1.6 mU/l) in insulinoma patients. Over the 12-h period blood glucose, pyruvate and glycerol were significantly lower, and plasma insulin, blood lactate, alanine and plasma non-esterified fatty acids (NEFA) significantly higher in insulinoma patients. Overall the concentration of blood total ketone bodies was significantly higher in insulinoma patients. Values were higher in the early part of the day but lower later in the day and did not show the marked pre-meal rise observed in the normal subjects. The raised NEFA and ketone bodies are of particular interest as they may be a source of fuel supply in the presence of relative glucose deficiency.

Following weight loss in massively obese patients correction of the insulin resistance of fat metabolism is delayed relative to the improvement in carbohydrate metabolism.

Intermediary metabolite and serum insulin concentrations have been measured during incremental intravenous low-dose insulin infusion in massively obese patients before, and 3 months and 12 months after gastroplasty. Fasting blood glucose was similar on the three occasions, but fasting serum insulin was significantly higher preoperatively and showed a progressive fall with weight loss. Significant negative linear correlations were found between serum insulin and blood glucose, plasma nonesterified fatty acids, blood glycerol and blood total ketone bodies concentrations. The insulin-glucose dose-response curve showed a significant left shift at 3 months with a further significant improvement at 12 months. No significant change in the responses for nonesterified fatty acids, glycerol, and ketone bodies was observed at 3 months, but all three showed a significant left shift at 12 months. Massively obese patients are resistant to the action of insulin on carbohydrate and fat metabolism. Weight loss following gastroplasty results in an improvement in sensitivity to insulin, which is evident earlier in carbohydrate metabolism than in fat metabolism.