Self-programming machines (II): Network of self-programming machines driving an Ashby homeostat.

The progress in artificial intelligence enables us to conceive adaptive systems whose characteristics are nearer and nearer to those of living beings. These characteristics though depend on ingenious choices by the designer of these systems: Initial conditions, parameters, optimisation functions, gradient and measure of fitness within the environment. Nevertheless, in living systems which are non-finalist, there are no programmers or designers to conceive of such ingenious choices. Our paper "Self-Programming Machines (I)" presents a non-finalist model since initial states and functions are randomly chosen at the beginning and once and for all. In spite of the fact that they are non-finalist, these machines always stabilise at fixed points when they are connected to an external process. This paper studies the dynamics of a mono-layered network of self-programming machines driving a real device. "the Ashby homeostat", and shows the striking properties of such networks. This system stabilises only at fixed points even if it is subjected to small perturbations or intentional breakdowns such as a reversal of power supply or disconnection of one or several motors. Real and simulated experiences are compared and theoretical results are demonstrated.

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.

[Self-modifying automata. Models allowing the understanding of the properties of self-programming of life and of the nervous system (some basic theorems)]. / Les automates automodificateurs. Modèle permettant la compréhension des propriétés d'autoprogrammation du vivant et du système nerveux (quelques thérorèmes de base).

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.

[Treatment of solar urticaria: advantage of terfenadine]. / A propos du traitement de l'urticaire solaire: intérêt de la terfénadine.

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.

[Attempt at quantification of the clinical picture of varices for epidemiologic, therapeutic and data-processing purposes]. / Essai d'une quantification clinique des varices pour l'épidémiologie, la thérapeutique et l'informatique.

The expression "presence of varices" does not mean it is possible to anticipate their importance. The use of qualifications such as large, average or small by no means solves the problems of their evaluation for they often take on a different meaning according to the interpretation of the observer. The authors suggest the use of a system of clinical evaluation whose chief characteristic is the measurement of the diameter of varices. In the field of epidemiological studies, quantification is subjected to the determination of a coefficient of maximal invasion (CMI). This is equal to the product of the maximal diameter (MD) of the varices present, by their total length (TL). CMI = MD X TL. The clinical quantification for therapeutics, that is, the quantification that can be used in daily practice, is more simple. It is achieved by the intermediary of three parameters the maximal diameter, the maximal number and height of the varices present in each area. The regular analysis of these three variables makes it possible to follow in figures, and therefore in a way which is readily transmissible, the mode of evolution of the varicose disease. Generally, this quantification completes the usual schemas, makes the teaching of sclerotherapy much easier, makes phlebology more accessible for computer data, with cartography as a basis for the anatomical reference points. The main interest in these two systems lies in the use of a simple language which can be easily understood by everyone, whatever their nationality, and this makes for a more exact appreciation of the work that has been carried out and results in much better communication.

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.

[Blood typing of a Hansen population in Guadeloupe (F.W.I.)]. / Etude hémotypologique d'une population hansénienne en Guadeloupe (F.W.I.).

The target of this survey carried out in Guadeloupe (F.W.I.) is to search for eventual relationship between leprosy forms and ethnic features--Made in people subjected to same environmental factors, such a study avoids usual bias of investigations on the epidemiological aspect of "racial" factors. The 1522 investigated patients have been divided into 2 categories: allergic paucibacillary (Mitsuda +), and anergic multibacillary (Mitsuda -) patients. -). Three parameters were studied: morphological type empirically determined according to cutaneous pigmentation; ABO blood groups; and Rhesus phenotype. The results bring to the fore: Significant linkage between clinical forms and morphotype: the dominant Caucasian morphological typed subjects, with integument poor in melanin, are more numerous among multibacillary patients. This might confirm high sensitiveness of Caucasians to leprosy. No significant linkage between clinical forms and ABO blood groups. Nevertheless, variations are found already reported in more homogeneous populations: predominance of A group in multibacillary patients, of B and O groups in paucibacillary patients. Significant linkage between clinical forms and Rhesus phenotype. But this link does not seem to be imputable to ethnic factors because clinical forms distribution is the same in ccDee sub-population (the most frequent in West Africa), and in ccddee subpopulation (quite frequent phenotype in West Europe). In fact, only the ccDEe phenotype sub-population is significantly different from all the others, because multibacillary forms are particularly frequent (49.3%) and strike evenly women and men in this sub-population.

Sustained initial remission induced by intensive insulin treatment in type I diabetes. Possible role of the genetic background.

A remission defined by the possibility of temporarily discontinuing insulin therapy while blood glucose remains normal is not infrequently observed after intensive insulin therapy in newly diagnosed acute type I diabetes in the South of France. In order to analyze possible factors of such a remission, 47 newly diagnosed ketotic diabetics under 35 years of age and of Caucasian origin were enrolled in a prospective study. They were given continuous s.c. insulin infusion for two weeks and oral agents were introduced on day 8. In 16 patients insulin could not be withdrawn. In 31 insulin was stopped for more than 3 months (mean 12.3, range 3-35) while blood glucose remained below 6 mmol/l fasting (mean 5.3) and 7.8 post-prandial (mean 5.1) and glycosylated Hb below 8.5% (mean 6). At presentation, diabetics who later went into remission and those who did not, showed no difference in age (22.3 vs 23.1 years), sex ratio, apparent duration of symptoms (1.4 vs 1.6 months), glycosylated hemoglobin (12.0 vs 13.1%) and basal or post-prandial C-peptide values or presence of islet cell antibodies. No differences were observed in the frequency of DR3 and DR4 antigens in the two groups but diabetics who developed a remission bore the A 19.2 antigen (9/31 vs 1/16) and the B18 one (11/31 vs 1/16) more frequently, A 19.2 and B18 being associated in 7 cases of this group. This increased frequency in the remission group of HLA antigens, more often observed in diabetics of Mediterranean origin, suggests that differences in the genetic background may be associated with a difference in the evolution of the disease.

[Initial remission period in insulin-dependent diabetes in the young subject]. / La phase de rémission initiale du diabète insulinodépendant du sujet jeune.

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.

[Specific immunologic resistance to bovine insulin in an insulin-dependent diabetic]. / Résistance d'origine immunologique spécifique à l'insuline bovine chez un diabétique insulino-dépendant.

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.

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.

[Evaluation of the acceptability of 2 methods for self monitoring of blood sugar by a group of insulin-dependent diabetic patients]. / Evaluation de l'acceptabilité de deux méthodes d'autosurveillance glycémique par un groupe de diabétiques insulinodépendants.

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.

[The artificial pancreas in surgery. An attempt to simplify intra- and post-operative insulin therapy]. / Le pancréas artificiel en chirurgie. Recherche d'une simplification de l'insulinothérapie per et post-opératoire.

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.

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.

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.