Reducing glycaemic variability in type 1 diabetes self-management with a continuous glucose monitoring system based on wired enzyme technology.

AIMS/HYPOTHESIS: This study was designed to investigate the use and impact of a continuous glucose monitoring system (the FreeStyle Navigator) under home-use conditions in the self-management of type 1 diabetes. METHODS: A 20 day masked phase, when real-time data and alarms were not available, was compared with a subsequent 40 day unmasked phase for a number of specified measures of glycaemic variability. HbA(1c) (measured by DCA 2000) and a hypoglycaemia fear survey were recorded at the start and end of the study. RESULTS: The study included 48 patients with type 1 diabetes (mean age 35.7 +/- 10.9, range 18-61 years; diabetes duration 17.0 +/- 9.5 years). Two patients did not complete the study for personal reasons. Comparing masked (all 20 days) and unmasked (last 20 days) phases, the following reductions were seen: time outside euglycaemia from 11.0 to 9.5 h/day (p = 0.002); glucose SD from 3.5 to 3.2 mmol/l (p < 0.001); hyperglycaemic time (>10.0 mmol/l) from 10.3 to 8.9 h/day (p = 0.0035); mean amplitude of glycaemic excursions (peak to nadir) down by 10% (p < 0.001); high blood glucose index down by 18% (p = 0.0014); and glycaemic risk assessment diabetes equation score down by 12% (p = 0.0013). Hypoglycaemic time (<3.9 mmol/l) decreased from 0.70 to 0.64 h/day without statistical significance (p > 0.05). Mean HbA(1c) fell from 7.6 +/- 1.1% at baseline to 7.1 +/- 1.1% (p < 0.001). In the hypoglycaemia fear survey, the patients tended to take less snacks at night-time after wearing the sensor. CONCLUSIONS/INTERPRETATION: Home use of a continuous glucose monitoring system has a positive effect on the self-management of diabetes. Thus, continuous glucose monitoring may be a useful tool to decrease glycaemic variability.

A 17-year epidemiological study on changes in lung function in toluene diisocyanate foam workers.

OBJECTIVE: To determine whether longitudinal declines in ventilatory capacity and the occurrence of respiratory symptoms in workers manufacturing polyurethane foam were related to toluene diisocyanate (TDI) exposure. METHODS: A population of workers from 12 UK factories was studied between 1981 and 1986 [8]. A survivor cohort of 251, of whom 217 were in the 1981-1986 study, was examined again in 1997-1998. Modified British Medical Research Council respiratory questionnaires and lung function measurements were completed for each of the 251 subjects at the beginning and end of the 17-year study period. Mean TDI exposures for all jobs in which subjects were employed were assessed and related to their occupational histories. RESULTS: The annual declines in 1-second forced expiratory volume (FEV(1)) and forced vital capacity (FVC) were not related to TDI exposure, and were typical of those measured in other populations not exposed to TDI. Over the study period the cold-foam handling group ( n=26) showed an increase in breathlessness and a significant excess decline in FVC; the exposed group ( n=175) showed an increase in wheezing (mainly smokers), whilst the low-exposure group ( n=50) showed a decrease in chest illness. Smoking and an increase in body weight both caused excess declines in FEV(1). CONCLUSIONS: This study does not provide evidence that there was any TDI-related decline in FEV(1) or in FVC over a 17-year period in workers exposed to TDI at the levels prevailing in the UK factories that manufactured flexible polyurethane foam.

Isocyanate exposure and occupational asthma: a case-referent study.

OBJECTIVE: To examine the quantitative relation between exposure to isocyanates and occupational asthma, and to explore the role of atopy and smoking in occurrence of the disease. METHOD: A case-referent study was undertaken of cases from two manufacturing companies (A and B) from which referents without disease could be selected and reliable exposure measurements were available. In company A, 27 cases mainly attributed to toluene diisocyanate (TDI) were matched to 51 referents on work area, start and duration of employment, sex, and age. Exposures were estimated from existing measurements by job category. In company B there were seven cases attributed to 4,4'-diphenylmethane diisocyanate (MDI) in two areas of the plant; 12 non-cases from the same areas were used as referents. Personal exposure measurements were available for all cases and 11 referents. RESULTS: No difference in peak exposures between cases and referents was found in either plant; but in both, time weighted average (TWA) exposures at the time of onset of asthma were higher for cases. In A, the mean TWA exposure for cases was 1.5 (95% confidence interval (95% CI) 1.2 to 1.8) ppb compared with 1.2 (1.0 to 1.4) ppb for referents. From a matched analysis, the odds ratio (OR) associated with 8 hour TWA exposure to isocyanates greater than 1.125 ppb (the median concentration for the referent group) was 3.2 (95% CI 0.96 to 10.6; p=0.06). Occupational asthma was associated with a pre-employment history of atopic illness (OR 3. 5, p=0.04) and, less strongly, with smoking (OR 2.1, p=0.14). In B, small numbers limited analysis, but three of seven cases had at least one TWA exposure measurement greater than 5 ppb compared with one of 11 referents (OR 7.5, p=0.09). CONCLUSION: Asthma can occur at low concentrations of isocyanates, but even at low concentrations, the higher the exposure the greater the risk. By contrast with other studies, smoking and atopy seemed to increase the odds of occupational asthma due to isocyanates, but did not affect the estimate of risk associated with exposure.

Host-guest interactions at self-assembled monolayers of cyclodextrins on gold

We have developed synthesis routes for the introduction of short and long dialkylsulfides onto the primary side of alpha-, beta-, and gamma-cyclodextrins. Monolayers of these cyclodextrin adsorbates were characterized by electrochemistry, wettability studies, X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (TOF-SIMS), and atomic force microscopy (AFM). The differences in thickness and polarity of the outerface of the monolayers were measured by electro-chemistry and wettability studies. On average about 70% of the sulfide moieties were used for binding to the gold, as measured by XPS. Tof-SIMS measurements showed that the cyclodextrin adsorbates adsorb without any bond breakage. AFM measurements revealed for beta-cyclodextrin monolayers a quasi-hexagonal lattice with a lattice constant of 20.6 A, which matches the geometrical size of the adsorbate. The alpha-cyclodextrin and gamma-cyclodextrin monolayers are less ordered. Interactions of the anionic guests 1-anilinonaphthalene-8-sulfonic acid (1,8-ANS) and 2-(p-toluidinyl)naphthalene-6-sulfonic acid (2,6-TNS) and the highly ordered monolayers of heptapodant beta-cyclodextrin adsorbates were studied by surface plasmon resonance (SPR) and electrochemical impedance spectroscopy. The SPR measurements clearly showed interactions between a beta-cyclodextrin monolayer and 1,8-ANS. Electrochemical impedance spectroscopy measurements gave high responses even at low guest concentrations (< or = 5 microM). The association constant for the binding of 1,8-ANS (K = 289,000 +/- 13,000M-1) is considerably higher than the corresponding value in solution. (Partial) methylation of the secondary side of the beta-cyclodextrin strongly decreases the binding.

The use of microdialysis to monitor rapid changes in glucose concentration.

As a result of the Diabetes Control and Complications Trial, there is increased emphasis on the importance of blood glucose concentration self-monitoring for people with diabetes. The current methods for this are not ideal, and there are many other possible techniques currently under investigation. One of these techniques is microdialysis, which can be used to analyse subcutaneous interstitial glucose concentrations. A system with high recovery has recently been used to monitor glucose concentrations with sampling over one- or two-hour periods. We have investigated whether this system can be used to monitor rapid changes in blood glucose concentration in healthy volunteers with collection intervals of only ten minutes. The results show that microdialysis can be used to monitor rapidly changing blood glucose concentration, but in some subjects, dialysate glucose lagged behind the whole blood and plasma glucose concentrations to a degree that would be clinically significant. It would therefore be necessary to assess the system, comparing dialysate with plasma glucose concentrations in each individual, prior to use in a clinical setting.

An epidemiology study of lung function changes of toluene diisocyanate foam workers in the United Kingdom.

OBJECTIVE: To determine whether longitudinal declines in ventilatory capacity and the occurrence of respiratory symptoms in workers manufacturing polyurethane foam were related to toluene diisocyanate (TDI) exposure. METHODS: A population of 780 workers in 12 United Kingdom factories was followed for 5 years. Modified United Kingdom Medical Research Council (MRC) respiratory questionnaires and three or more lung function measurements were completed for each subject. Mean TDI exposures for all jobs in which subjects were employed were assessed by personal monitoring (2294 measurements) and related to their occupational histories. RESULTS: The United Kingdom 8-h and 15-min maximum exposure limits for TDI were exceeded in 4.7% and 19.0% of the samples taken, respectively. There was some increase in reported respiratory symptoms amongst exposed workers, but the annual declines of 1-s forced expiratory volume (FEV1) and forced vital capacity (FVC) were not related to TDI exposure and were typical of those observed in other longitudinal populations. FEV1 declines were smoking-related. Evidence was found suggesting that a small excess decline in FEV1 and FVC occurred in the first few years of employment for workers not previously exposed to TDI. CONCLUSION: This study does not provide evidence that there is a TDI-related decline in FEV1 and FVC in workers exposed to less than the United Kingdom 8-h occupational exposure limit of 5.8 ppb.

Sternomastoid muscle fatigue and twitch maximum relaxation rate in patients with steroid dependent asthma.

BACKGROUND: Long term oral corticosteroid treatment is a cause of myopathy of the skeletal muscles. The effect of long term treatment with oral corticosteroids on the respiratory muscles is uncertain. Respiratory muscle function and fatigue in sternomastoid muscle were investigated in a group of patients with chronic severe asthma who were taking oral corticosteroids. The results were compared with those from a group of patients with chronic airflow limitation who were not taking oral steroids. METHODS: Twelve patients with chronic severe asthma, taking a mean daily dosage of 8 mg of prednisolone for a mean (SD) of 16.8 (9.1) years, were compared with patients with chronic airflow limitation and individually matched for sex, age, and severity of airflow limitation. Lung function tests, maximal mouth pressures, and quadriceps and sternomastoid muscle strength were measured. The sternomastoid muscle was fatigued by maximal headlift exercise to 70% of initial headlift force and the endurance time noted. Sternomastoid fatigue was assessed by twitch maximum relaxation rate (TMRR) measured in the fresh state and for 30 minutes after exercise. RESULTS: There was no significant difference between the control group and the corticosteroid group for maximal mouth pressures, fresh state TMRR, and quadriceps and sternomastoid strength. The control group had a significantly longer mean (SD) endurance time than the corticosteroid group (121 (47) s v 86 (24) s), and also had significantly less slowing and faster recovery of the TMRR after exercise. The slowing and recovery of the TMRR in the corticosteroid group, however, was similar to that previously reported for normal subjects. CONCLUSION: Respiratory muscle weakness does not occur more often in patients taking oral corticosteroids. The corticosteroid group was more prone to fatigue than the control group, but was similar to normal subjects. This suggests that chronic airflow limitation may produce a training effect on the respiratory muscles that might be attenuated by long term oral corticosteroid treatment.

Value of pulse oximetry in screening for long-term oxygen therapy requirement.

Pulse oximetry, combined with spirometry, was evaluated as a method of selecting chronic obstructive pulmonary disease (COPD) out-patients requiring definitive arterial blood gas analysis for long-term oxygen therapy (LTOT) assessment. A relatively high screening arterial oxygen saturation by pulse oximetry (SaO2) level was set, in order to maximize sensitivity. All 113 COPD out-patients attending the hospital clinic over a 6 month period were screened. Sixty had a forced expiratory volume in one second < 1.5 l and 26 had an SaO2 < or = 92%. These 26 underwent arterial blood gas analysis. Nine had an arterial oxygen tension < 7.3 kPa all with an arterial carbon dioxide tension (PaCO2) > 6 kPa. A further eight had a PaO2 < 8 kPa. This produced a sensitivity of 100% and specificity of 69% for oximetry in the detection of PaO2 < 7.3 kPa determined by direct arterial puncture and 100% and 86% respectively for detecting a PaO2 < 8 kPa. Although the poor specificity of oximetry in the crucial PaO2 range makes it unsuitable, when used alone, for prescription of LTOT, it may prove valuable in selecting patients who require further definitive arterial blood gas analysis.

Effect of arterial oxygen desaturation on six minute walk distance, perceived effort, and perceived breathlessness in patients with airflow limitation.

BACKGROUND: The effect of exercise induced hypoxaemia in determining submaximal exercise capacity, perceived breathlessness, and perceived exertion is not known. The purpose of this study was to investigate the relation of these variables to the results of lung function tests and the degree of hypoxaemia during submaximal exercise in patients with airflow limitation. METHODS: Forty two patients with chronic obstructive airways disease and 28 patients with chronic severe asthma were studied. Spirometry was performed and gas transfer (TLCO) and lung volumes were measured. Submaximal exercise capacity was assessed with a standardised six minute walk test. Arterial oxygen desaturation during the walk test was monitored by a portable pulse oximeter. Patients rated their perceived degree of respiratory impairment on a Medical Research Council (MRC) breathlessness scale before the walk. Perceived breathlessness was measured by means of a linear visual analogue scale and exertion on the Borg scale after the walk. RESULTS: The six minute walk distance was strongly correlated (r value) with TLCO (0.68), peak expiratory flow (PEF: 0.55), forced expiratory volume in one second (FEV1: 0.53), transfer coefficient KCO: 0.49), age (-0.49), and forced vital capacity (FVC: 0.48) but not with oxygen desaturation during the walk. Walk distance was also correlated with the breathlessness rating on the MRC scale (-0.52), but less strongly with perceived breathlessness (-0.35) and perceived exertion (-0.30). The prediction equation for the six minute walk distance in metres (6MD) generated by multiple regression analysis was 6MD = 387 + 29.7 (TLCO) -3.1 (age) + 0.35 (PEF 1/min), which accounted for 50% of the total variance in walk distance. The mean level of saturation during the walk correlated most significantly with TLCO (0.55), FEV1/FVC (0.54), and PEF (0.48), but not with walk distance or with the rating on any of the analogue scales. The prediction equation produced by multiple regression analysis for the mean level of saturation during the walk was MEANSAT(%) = 1.3(TLCO) + 1.5 (base-line saturation) - 0.01 (6MD) - 54. CONCLUSIONS: Oxygen desaturation during the six minute walk is not related to walk distance, nor does it determine the degree of perceived exertion or perceived breathlessness in patients with airflow limitation. Patients who consider themselves the most disabled by breathlessness have the shortest six minute walk distance but do not necessarily have appreciable desaturation.

A within-patient comparison of debrisoquine and methyldopa in hypertension.

In a titrated dose cross-over trial of debrisoquine and methyldopa in 38 hypertensive patients neither drug was superior in lowering supine or standing diastolic pressure with a minimum of side effects. Methyldopa caused significantly greater reduction of supine (P<0.001) and standing (P<0.02) systolic pressure but caused intolerable side effects in two patients. Tiredness was the most characteristic and troublesome side effect with methyldopa and postural hypotension was prominent in patients while on debrisoquine.