Rapid restoration of normoglycaemia using intravenous insulin boluses.

The reduction of elevated fasting plasma glucose levels to near normal by repeated intravenous bolus insulin doses, given according to a simple algorithm, has been studied in 17 Type I and 23 Type II, healthy diabetic patients. Using a formula based on the patient's plasma glucose, height and bodyweight with insulin boluses given every 30 min if the plasma glucose remained above 6 mmol/1, plasma glucose levels were reduced to less than 7.5 mmol/1 in 28 (70%) patients by 60 min at which time the mean (+/- 1 SD) plasma glucose level in the Type I diabetic patients had reduced from 18.2 +/- 4.9 to 8.9 +/- 3.5 mmol/1 and in the Type II diabetic patients from 12.3 +/- 3.1 to 5.9 +/- 1.4 mmol/1. None of the patients had symptomatic hypoglycaemia although in one Type I patient the plasma glucose level fell to 2.2 mmol/1. The rate of fall of glucose in the less insulin sensitive patients was not increased by giving more insulin. The regimen allows a reproducible and prompt glycaemic reduction in fasting diabetic patients.

A visual assessment of a young multiply handicapped girl and an associated teaching programme.

An attempt to obtain a visual assessment of a five-year-old girl with severe learning difficulties using a picture test of visual acuity failed because the girl was unable to name or match any of the pictures. A teaching programme was then undertaken by the girl's class teacher, after which the girl was successfully retested some 4 months later.

Dependence of calcium permeability of sarcoplasmic reticulum vesicles on external and internal calcium ion concentrations.

The ability of sarcoplasmic reticulum vesicles to retain calcium following ATP-supported calcium uptake in the presence of the calcium-precipitating anions oxalate and phosphate depends on Cao (calcium ion concentration outside the vesicles) and Cai (calcium ion concentration within the vesicles). Calcium efflux rates at any level of Cai are accelerated when Cao is increased. Higher Cao at the time that calcium uptake reactions reach steady state is associated with a spontaneous calcium release that reflects this effect of increased Cao. Increasing Cai at any level of Cao causes little or no acceleration of calcium efflux rate so that calcium permeability coefficients, estimated by dividing calcium efflux rates by Cai, the "driving force", are inversely proportional to Cai. Calcium permability coefficients thus correlate, as a first approximation, with the ratio Cai/Cao, decreasing 1000-fold as this ratio increases over a 3000-fold range (Cao = 0.1 to 3.3 muM, Cai =4 to 750 muM). Oscillations in both the calcium content of the vesicles and Cao are seen as calcium uptake reactions approach steady state, suggesting that calcium permeability undergoes time-dependent variations. Sudden reduction of Cao to levels that markedly inhibit calcium influx via the calcium pump unmasks a calcium efflux that decreases slowly over 60 to 90 s. The maximal calcium permeability observed in the present study would allow the calcium efflux rate from the sarcoplasmic reticulum at a Cai of 100 muM to be approximately 10(-10) mol/cm2/s, which is about 1 order of magnitude less than that estimated for the sarcoplasmic reticulum of activated skeletal muscle in vivo. The release of most of the stored calcium in some experiments indicates that the observed permeability changes can occur over a large portion of the surface of the sarcoplasmic reticulum.

Substitution of phosphate for oxalate in the study of calcium accumulation and release by cardiac microsomal fractions.

Phosphate-supported calcium uptake by guinea pig cardiac sarcoplasmic reticulum has been shown to exhibit a pattern different from that of oxalate-supported calcium uptake. Ionophore-induced calcium release has been demonstrated following phosphate-supported calcium uptake. Rat cardiac sarcoplasmic reticulum has been shown to differ from the guinea pig in its sensitivity to ionophore.

A possible explanation for the peculiar contractile behavior displayed by rat heart muscle.

Because it is generally agreed that the sarcoplasmic reticulum plays an important role in regulating the intracellular availability of Ca2+, the ability of rat microsomal fractions to accumulate Ca2+ was compared with that of microsomal fractions similarly prepared from guinea pig heart muscle. Despite a relatively high level of basic ATPase enzyme activity (19.2 +/- 2.6 muM Pi/mg of microsomal protein/10 min) rat microsomal fractions consistently accumulated significantly (p less than 0.001) less Ca2+ than did the guinea pig preparations, irrespective of whether the incubation medium contained oxalate. The microsomal yield obtained from the rat hearts was not significantly different (p less than 0.8) from that obtained for guinea pig heart muscle. Rat mitochondria similarly accumulated significantly less Ca2+ than did the guinea pig mitochondria. These observations substantiate a general hypothesis that rat heart cells may possess a relatively high intracellular concentration of free Ca.