Greater efficacy of pulsatile insulin in type I diabetics critically depends on plasma glucagon levels

The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic patients proven to have no residual insulin secretion were investigated. Endogenous glucagon secretion was inhibited by a continuous intravenous infusion of somatostatin (100 micrograms/h) and replaced by exogenous infusions of the hormone at three different rates (7.5, 4.5, and 2.5 micrograms/h), resulting in three different plasma glucagon steady-state levels (i.e., approximately equal to 200, approximately equal to 130, and approximately equal to 75 pg/ml, respectively). Each subject, in random order and on different days, was infused intravenously with regular human insulin either continuously (0.17 mU X kg-1 X min-1) or with the same amount of insulin infused in a pulsatile manner (0.85 mU X kg-1 X min-1 during 2 min followed by 8 min during which no insulin was infused). At plasma glucagon levels approximately equal to 200 pg/ml, blood glucose rose from approximately 10 to approximately 13 mM without any difference between the two modalities of insulin infusion. For plasma glucagon levels approximately equal to 130 pg/ml, plasma glucose remained steady throughout the experiments, but during the last 40 min, plasma glucose levels were significantly lower when insulin was administered intermittently. This greater blood glucose-lowering effect of pulsatile insulin occurred earlier and was more pronounced for plasma glucagon levels averaging 75 pg/ml. We conclude that the greater hypoglycemic effect of insulin administered intravenously in a pulsatile manner in type I diabetics critically depends on plasma glucagon circulating levels.     

An analysis of the paradoxical effect of morphine on runway speed and food consumption

A previously reported paradigm in which rats run down a runway for food reward followed by morphine injection was analyzed to assess the utility of the paradigm in studies of opiate reinforcement. One experiment replicated the original report that post-trial morphine caused both an increase in runway speed and a decrease in food consumption (taste aversion) over successive trials, and showed in addition that the increase in runway speed did not occur as a result of food deprivation alone, but required the animals to have consumed food in the goal box. A second study using the quaternary opiate antagonist methyl naltrexone to block the peripheral effects of morphine suggested that the increase in runway speed has a peripheral locus while the taste aversion has a central one. A third experiment in which morphine was microinjected into either the lateral ventricle or the ventral tegmental area supported these observations, in that intracranial morphine failed to result in an increased runway speed, but did produce taste aversion after microinjection into either site. These findings also suggest that the increase in runway speed caused by post-trial morphine in this experiment has a peripheral locus of effect, which is probably distinct from the central effect that supports morphine self-administration and conditioned place preference. Offprint requests to: W.A.CorrigallThe views expressed in this publication are those of the authors and do not necessarily reflect those of the Addiction Research Foundation     

What is the place of electroneuromyographic studies in the diagnosis and management of pudendal neuralgia related to entrapment syndrome?

Entrapment of the pudendal nerve may be at the origin of chronic perineal pain. This syndrome must be diagnosed because this can result in the indication of surgical decompression of the entrapped nerve for pain relief. Electroneuromyographic (ENMG) investigation is often performed in this context, based on needle electromyography and the study of sacral reflex and pudendal nerve motor latencies. The limits of ENMG investigation, owing to various pathophysiological and technical considerations, should be known. The employed techniques do not assess directly the pathophysiological mechanisms of pain but rather correlate to structural alterations of the pudendal nerve (demyelination or axonal loss). In addition, only direct or reflex motor innervation is investigated, whereas sensory nerve conduction studies should be more sensitive to detect nerve compression. Finally, ENMG cannot differentiate entrapment from other causes of pudendal nerve lesion (stretch induced by surgical procedures, obstetrical damage, chronic constipation...). Thus, perineal ENMG has a limited sensitivity and specificity in the diagnosis of pudendal nerve entrapment syndrome and does not give direct information about pain mechanisms. Pudendal neuralgia related to nerve entrapment is mainly suspected on specific clinical features and perineal ENMG examination provides additional, but no definitive clues, for the diagnosis or the localization of the site of compression. In fact, the main value of ENMG is to assess objectively pudendal motor innervation when a surgical decompression is considered. Perineal ENMG might predict the outcome of surgery but is of no value for intraoperative monitoring.     

Recommendations from a multi-study evaluation of proposed criteria for staging reproductive aging.

In 2001, the Stages of Reproductive Aging Workshop (STRAW) proposed bleeding and endocrine criteria for defining the early and late menopausal transition stages. Based on expert consensus, STRAW recommended a shorter interval of amenorrhea than the commonly used 90-day amenorrhea criteria for late transition and a >7-day change in cycle length for early transition. The ReSTAGE collaboration used prospective menstrual calendar data from four cohorts (TREMIN, Melbourne Women's Midlife Health Project, Seattle Midlife Women's Health Study, and Study of Women's Health Across the Nation) to quantitatively evaluate STRAW's recommendations. This empirical assessment supported the STRAW recommendations that (1) > or =60 days of amenorrhea be used to define the late menopausal transition and (2) that early transition is consistent with a persistent 7 or more day difference in length of consecutive cycles. Serum follicle stimulating hormone (FSH) values > or =40 IU/l was an independent marker of the transition and, when occurring together with a bleeding marker, increased prediction of final menstrual period. Such a FSH criterion could be incorporated into the STRAW paradigm to facilitate prediction of proximity of the final menstrual period.     

Role of alpha and beta cells in the impaired glucose tolerance of thalassaemic subjects

Fifty healthy and 12 thalassaemic subjects underwent both an oral glucose tolerance test (OGTT) and arginine test in order to investigate their alpha and beta cell activity. While basal plasma levels were similar in both group of subjects (82 +/- 4 vs 74 +/- 4 mg/dl, p = NS), following glucose intake impaired glucose tolerance was observed in thalassaemic subjects. These subjects showed impaired insulin secretion either in steady-state conditions or after glucose intake. When an arginine test was performed in thalassaemic subjects, impaired insulin secretion with concomitant exaggeration of glucagon response was also observed. In the thalassaemic subjects no statistically significant correlations were found between impaired insulin secretion and iron overload. It is suggested that in thalassaemic subjects beta-cell dysfunction and alpha cell overactivity may lead to the development of diabetes mellitus.     

Medical treatments of hyperactive child]

Treatment of hyperactive child is multimodal, a combination of behaviour therapy and medication. Stimulant drugs are the most often prescribed medications. In France, we use methylphenidate (Ritaline); its efficacy was demonstrated with mild side effects. New formulations of methylphenidate with prolonged action, and non-psychostimulant treatment (atomoxetine) are available in some countries, but not yet in France.     

On the subject of the cyclic vomiting syndrome]

The cyclic vomiting syndrome is defined by episodes of vomiting lasting from hours to days with free intervals between episodes. Various symptoms can be associated with vomiting: nausea, abdominal pain, photophobia, fever, pallor, dehydratation, excess salivation, social withdrawal. Some factors often precipitate the crisis: infection, psychological stresses, menstruation. Excluding a medical condition, especially a gastro-intestinal or a neurological disease is compulsory for the diagnostic of cyclic vomiting syndrome. The cyclic vomiting syndrome shares many common features with migraine including treatment. Due to negative paraclinical testing, a psychiatric disease is often suspected in these children. Pathophysiology of cyclic vomiting syndrome is unknown. As for migraine, mitochondrial and ionic channels abnormalities are thought to play a role. Overactivation of hypothalamic-pituitary-adrenal axis and autonomic dysfunction seem to be involved too. Three clinical vignets will illustrate these aspects.     

Normal EEG of premature infants born between 24 and 30 weeks gestational age: terminology, definitions and maturation aspects.

This article presents normal EEG characteristics and their maturational pattern in premature infants of 24-30 weeks gestational age. Although the very premature infants with a normal outcome are not that numerous, their normal EEG pattern should be known, as EEG constitutes a basis for neurological prognosis. Background activity is first discontinuous but the discontinuity gradually decreases and the activity is completely continuous at 30 weeks of age, during active sleep. At the same time, interburst intervals become shorter so that the proportion of time without EEG activity decreases. Based on EEG activity and eyes movements, a rough sleep state differentiation appears as early as 25 weeks of gestational age and is complete at 30 weeks. The main EEG figures are high-voltage delta waves, whose frequency is slower and amplitude higher in younger infants. Temporal delta waves occur in sequences and are characteristic of the very premature infant; they progressively become smaller and less numerous and disappear around 27-28 weeks. In contrast, occipital delta waves remain numerous; they are of high voltage and usually bilaterally superimposed with fast rhythms. Both types of frontal delta waves that are seen in 24-27 weeks premature babies disappear with maturation. Bursts of synchronized delta waves, which are less numerous than localized delta waves, also disappear before 28 weeks of gestational age. Finally, diffuse theta bursts which are mainly recorded at 26-27 weeks, progressively focus on temporal areas with maturation. At 30 weeks, they are observed on temporal areas, mainly during slow-wave sleep.     

Necrotizing pneumonia and arthritis due to Staphylococcus aureus producing Panton and Valentine leukocidin in a 10-year-old boy]

Staphylococcal necrotizing pneumonia producing the Panton Valentine leukotoxin (PVL) has been described for many years. The french reference center for staphylococcal toxaemia defined it with precision in 1999. A 10-year-old child, died in 36 hours from respiratory distress and shock. Staphylococcal pneumonia was suspected then confirmed: S. Aureus producing PVL was isolated in lung, blood and articulations.