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Biomedical subjects

J P Moulin

Publications and source records attributed to J P Moulin.

At least 19 recordsLinked to original sources

Modifiable automata self-modifying automata.

One of the most important features of living beings that seems universal is perhaps their ability to be modified in a functional way. In order to modelize this characteristic, we designed automata with a finite number of instantaneous internal descriptions, with input(s) and output(s) and which are able to be functionally modified. The rules which govern the evolution of these automata (and the initial conditions) are randomly chosen at the beginning and once and for all. When such an automaton is linked by its input and output to a deterministic process, it always stabilizes and it then has the property to rebuild itself. Thus it made a function which is inverse of the external function. We demonstrate the prevalence of p = 1 length period and of tau = 0 transient length for automata with m instantaneous internal descriptions.

Animals

[Self-modifying automata. Models allowing the understanding of the properties of self-programming of life and of the nervous system (some basic theorems)].

In an attempt to discover the properties of the nervous system, we imagined the conditions under which a machine would be able to construct its own program and from which emerged the model of Self Modifying Automata (SMA). We demonstrated the unicity of the SMA model, their convergence in a p-cycle and, in this case, the SELFREFERENCE of a stabilised SMA (it then generates its own program), their adaptability when connected to a deterministic world. The SMA reaches its p-cycle very quickly and the most probable length of the -cycle is 1.

Animals

[Treatment of solar urticaria: advantage of terfenadine].

Solar urticaria is a rare photodermatosis, but it is extremely incapacitating and therapy is usually ineffective. Three patients who took a daily dose of 240 mg terfenadine were able to be normally exposed to sunlight. This efficacy was confirmed by photobiological tests. The minimal dose necessary to induce urticaria was increased at least three times. These results confirming recently published ones. Terfenadine at 240 mg per day seems to be the treatment of choice for solar urticaria because of its efficacy and excellent tolerance-especially as there is no sedative effect.

Adult

Mechanism and significance of insulin resistance in myotonic dystrophy.

In order to elucidate the mechanism of the glucose intolerance frequently associated with myotonic dystrophy (MD), glucose metabolism of 10 patients and 10 controls was investigated using the following tests: successive intravenous stimulation of insulin secretion by glucose and tolbutamide, detection of serum islet cell antibodies, measure of the specific insulin binding on erythrocytes and evaluation in vivo of insulin sensitivity by the euglycaemic glucose clamp method. Glucose tolerance was decreased in MD patients (K value: 1.51 +/- 0.15 vs 2.4 +/- 0.2 X 10(-2)) in spite of a basal (26 +/- 4 vs 11 +/- 2 microU/ml) and post-stimulative hyperinsulinism (area of the plasma insulin curve after glucose IG: 642 +/- 120 vs 315 +/- 28 microU/ml/min and area after tolbutamide IT: 740 +/- 166 vs 335 +/- 35 microU/ml/min). No islet cell antibody was detected in the serum of MD patients. These results suggest that decrease of glucose tolerance is secondary to peripheral insulin resistance. Specific binding of insulin on erythrocytes was slightly but not significantly reduced in MD patients (specific binding: 8.21 +/- 0.9 vs 9.64 +/- 0.9%, receptor number: 23 +/- 2 receptors/cell, concentration of unlabelled insulin displacing 50% of the bound radioactivity: 7.2 +/- 0.56 vs 6.6 +/- 0.6 ng/ml). There was a loss of normal down regulation of insulin receptors in MD. The results of the euglycaemic glucose clamp confirmed the insulin resistance especially for the highest insulin infusion rates. These data show that the insulin resistance of MD is due to both receptor- and post receptor-defect but that the main abnormality is an unresponsiveness located after the insulin signal on the receptor.

Adult

[Initial remission period in insulin-dependent diabetes in the young subject].

Occurrence of a remission after initiation of insulin treatment in insulin dependent diabetes (type I) of recent onset is a well known phenomenon. It may be more or less complete up to insulin withdrawal. In newly diagnosed IDD requiring insulin for ketoacidosis or primary failure of oral agents and with a duration of symptoms of less than 6 months, initiation of optimized insulin therapy was followed by suppression of insulin (with or without the use of oral agents) in two thirds of cases for a mean period of 12 months while blood glucose and glycosylated haemoglobin remained normal. As therapeutic reversal of the etiopathological mechanism of IDD is foreseen it is relevant to define the characteristics of cases with remission induced by intensified insulin treatment, and the mechanisms by which they may be explained. Current knowledge on these questions will be analysed in this review. Furthermore it appears that withdrawing insulin for a mean period of 12 months does not hamper the subsequent control of diabetes.

Adolescent

[Specific immunologic resistance to bovine insulin in an insulin-dependent diabetic].

A 60-year old male diabetic patient treated with insulin for 6 years developed ketosis whenever an attempt was made to replace porcine insulin by mixed bovine and porcine insulin. That this resistance was specific to bovine insulin and of immune origin was demonstrated by in vivo and in vitro studies. The in vivo study used a Biostator artificial pancreas: rapid decrease of plasma glucose concentrations was observed under insulin infusion at a constant rate of 200 mU/min with either porcine or semi-synthetic human insulin despite maximum glucose infusion rate (400 mg/min), but not with bovine insulin and a low glucose infusion rate (150 mg/min). In the in vitro study, high levels of anti-insulin antibodies (11.4 m U/ml, Christiansen method) were found in the plasma, and the curves of competitive binding of radiolabelled insulin to the patient's IgG in the presence of unlabelled porcine or bovine insulin showed a 50% decrease of total binding with 0.12 ng/ml of bovine insulin and 25 ng/ml of porcine insulin, suggesting that the affinity of these antibodies for the former was 200 times higher than for the latter.

Animals

[Evaluation of the acceptability of 2 methods for self monitoring of blood sugar by a group of insulin-dependent diabetic patients].

In order to evaluate the advantages and disadvantages of two methods of blood glucose self-monitoring (either direct semi-quantitative reading on Haemoglukotest 20-800 or quantitative reading of Dextrostix strips using a reflectance-meter, Glucometer) 20 insulin-dependent diabetics selected according to the quality of the management of their own diabetes were asked to try both methods for 3 months and then fill a questionnaire assessing their acceptance. Analysis of the responses shows that home blood glucose monitoring is well accepted even after one year by patients aware of the necessity of a good glycemic control. It is specially useful for the adaptation of insulin doses and less so for identification of hypoglycemic attacks. Haemoglukotest 20-800 is appreciated for its easy utilization specially during professional life and outside leisure. However, the reflectance-meter Glucometer is preferred by most patients because they feel it is more reliable and safe.

Adolescent

Overnight basal insulin requirements in insulin dependent diabetics.

Programming open loop insulin delivery systems makes necessary the knowledge of patients insulin needs. It is frequently postulated that insulin needs increase at the end of the night in relation to the rise in cortisol secretion. According to this hypothesis is it justified to speed up the insulin infusion rate in the early morning? This question was addressed by studying insulin infusion rate by an artificial pancreas during the night in 12 C. peptide negative insulin dependent diabetics. They were connected to the artificial pancreas from 8 a.m. to 10 a.m. the next morning while on their habitual diabetic diet and slept as usual from 11 p.m. to 7 a.m. approximately. From 11 p.m. to 7 a.m. mean insulin infusion rate was 21.5 +/- 3.3 mU/Kg/h representing 15.6 +/- 1.6% of the dose delivered in 24 hours. Blood glucose was stable around 85 mg/dl. No significant differences were observed in the hourly insulin infusion rate during the night period, in spite of a slight tendency to a rise (from 21.1 +/- 2.8 to 22.1 +/- 2.6 mU/kg/h) tendency to a rise (from 21.1 +/- 2.8 to 22.1 +/- 2.6 mU/kg/h) after 4 a.m. On the basis of these results obtained in patients sleeping as usual it does not appear useful to envisage a systematic acceleration of insulin infusion rate by continuous delivery systems in the early morning.

Adult

[The artificial pancreas in surgery. An attempt to simplify intra- and post-operative insulin therapy].

The insulin requirements of 10 insulin-dependent diabetic patients were evaluated during and after surgery (including 4 caesarian sections) by connecting the patients with an artificial pancreas. Considerable variations were observed in the intra-operative period. In contrast, the amounts of insulin released during the immediate post-operative period were more regular and reproducible (mean: 2.36 U/h for a glucose intake of 200-250 g/24 h). A satisfactory control of glycaemia was obtained with this dosage in 7 insulin-dependent post-operative patients without using an artificial pancreas. It would therefore seem that in most cases continuous insulin infusion combined with direct measurement of capillary glycaemia could replace an artificial pancreas and make the intra- and post-operative care of diabetic patients simpler and more effective.

Adult

Abnormalities of erythrocyte deformability and platelet aggregation in insulin-dependent diabetics corrected by insulin in vivo and in vitro.

Erythrocyte deformability is lower than normal in uncontrolled insulin-dependent diabetics and returns towards normal after 24 h treatment with a feedback-controlled insulin infusion. Deformability of normal erythrocytes is reduced by incubation in plasma from uncontrolled insulin-dependent diabetics but is normal in plasma from insulin-dependent diabetics controlled by 24 h insulin infusion, or in plasma from uncontrolled insulin-dependent diabetics with insulin added in vitro. Therefore, insulin has a direct action on erythrocyte deformability. Platelet aggregation measured in whole blood is raised in uncontrolled insulin-dependent diabetics and returns to normal after 24 h treatment with a feedback-controlled insulin infusion. Aggregation of normal platelets rises in the presence of erythrocytes from uncontrolled insulin-dependent diabetics, but not erythrocytes from the same patients after 24 h treatment with insulin. The effect of insulin on platelet aggregation therefore seems to be at least partly mediated by erythrocytes. The enhanced platelet aggregation seen in uncontrolled insulin-dependent diabetics can be explained either by a direct effect of erythrocyte rigidity or by an increased release of nucleotides (ADP) by the erythrocytes.

Diabetes Mellitus

The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycaemia.

In non insulin dependent diabetics (N.I.D.D.) of normal body weight, the acute insulin response to glucose is defective while that to pharmacologic agents such as tolbutamide is less impaired. This specific B-cell insensitivity to glucose results from unknown and perhaps multiple mechanisms. Hyperglycemia may be itself aggravate this phenomenon. To test this hypothesis acute insulin release (delta I: sum of increment at 2, 5, 10 min) after intravenous and tolbutamide injection was studied in 5 N.I.D.D. with fasting blood glucose averaging 12.1 mM/I (range 10.7-13.7) before and after 20 hours of glycemic normalization by an artificial pancreas. Intravenous injection of .3 g/k glucose did not elicit an acute insulin or C-peptide response, but following Tolbutamide (20 mg/kg) delta I was 44 +/- 21 microU/ml and delta C-peptide 0.84 +/- 0.37 nM/I. After 20 hr of normoglycemia a response to glucose was apparent (delta I 60 +/- 24 and delta CP 0.86 +/- 26) that to Tolbutamide was unchanged (delta I 58 +/- 26 and delta CP 0.97 +/- 0.27). These results suggest that 20 hr of normoglycemia improve significantly the "glucoreceptor" function of the B-cell in N.I.D.D.

Adult

[Plasma lipid fractions in insulin-dependent diabetic patients. Effects of short-term control of glycaemia (author's transl)].

In order to elicitate a possible influence of short-term control of glycaemia on circulating plasma lipid fractions, the authors have endeavoured to find out: (a) whether there was a correlation between these fractions and glycosyl-haemoglobin (Hb A1) which indicates previous glycaemic balance, and (b) whether the various lipid fractions were modified by absolute control of glycaemia during a 24-hour application of artificial pancreas. They found that HbA1 correlated positively with total cholesterol and VLDL + LDL cholesterol, but not with HDL cholesterol. After 24 hours on artificial pancreas there was a significant decrease in total blood cholesterol without changes in blood triglycerides. The decrease was homogenous and concerned cholesterol concentrations in both low and high density lipoproteins. The authors conclude that the increased risk of atherosclerosis in insulin-dependent patients is in-related to a decrease in HDL cholesterol.

Adult

Effects of insulin on erythrocyte deformability in diabetics--relationship between erythrocyte deformability and platelet aggregation.

Erythrocyte deformability was studied by the filtration technique of Reid & Dormandy using whole blood and washed erythrocytes from insulin-dependent diabetics (IDD) under insulin delivery by an artificial pancreas (AP). The same technique was employed to study deformability in vitro using normal erythrocytes incubated in the presence of insulin. Results of this study show that in IDD the initially poor erythrocyte deformability is improved within hours of insulin administration. Improved deformability was accompanied by increased levels of intra-erythrocyte ATP but without changes in levels of HbG and 23 DPG. Incubation of erythrocytes in medium containing glucose showed that deformability was significantly improved in the presence of insulin. These results indicate that insulin favourably affects erythrocyte deformability in IDD. Before and after 24 hours treatment by AP, platelet aggregation was studied in IDD by the technique of Born using platelet-rich plasma (PRP) and by a modified Breddin technique using PRP, whole blood or whole blood treated by chlorpromazine and mixtures of erythrocytes from IDD with normal PRP. Platelet hyperaggregation was only found in the presence of erythrocytes from untreated diabetics. Chlorpromazine, at a dose (10 mumole) which inhibits haemolysis without inducing platelet hyperaggregation, eliminated the above anomaly. In conclusion, it is conceivable that the insulin-induced correction of poor erythrocyte deformability eliminates excessive fragility of erythrocytes and their haemolysis wit release of ADP, thus avoiding platelet hyperaggregation.

2,3-Diphosphoglycerate