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Abstract: An 80-year-old man had to be operated for cutaneous neoplasia. Local anaesthesia with sedation was required. Preoperative examination revealed a pronounced albeit asymptomatic bradycardia. Electrocardiogram showed a complete atrioventricular block. Use of a pacemaker was discussed. Finally, surgery was performed uneventfully after transient reversal of the anticholinesterasic effects of galantamine administered in Alzheimer''s disease control over several hours with atropine. [Copyright &y& Elsevier]

Purpose. – Multiple endocrine neoplasias (MEN) are autosomal dominant inherited syndromes characterized by the association of different glandular lesions in several members of the same kindred. The main clinical features of MEN 1 include primary hyperparathyroidism, pancreatic islet cell tumors and pituitary adenomas; less common features are adrenal adenomas, thymic and bronchial carcinoid tumors, lipomas and various cutaneous lesions. The MEN 2 syndromes (MEN 2A, MEN 2B and familial medullary thyroid carcinomas) are characterized by high penetrance of medullary thyroid carcinoma and differ in their variable expression of pheochromocytoma, hyperparathyroidism and other clinical features.Current knowledge and key points. – MEN 1 tumor suppressor gene encodes a nuclear protein, menin, which interacts with different regulation transcription factors. The MEN 2 syndromes are caused by germ-line mutations of the RET proto-oncogene, which encodes a transmembrane tyrosine kinase. Genetic testing for mutations in these 2 genes allows identification of individuals predisposed to the disease, early diagnosis, and clinical and therapeutic management.Future prospects and projects. – Fondamental approach will allow a best comprehension of physiopathogenic mechanisms of these disorders and the improvement of therapeutic management. [Copyright &y& Elsevier]

Objectives: The article aims to describe tobacco and e-cigarette use among pregnant women: estimate the prevalence, identify the determinants and motivations of these behaviours., Methods: Cross-sectional, multicentre, descriptive observational study using self-administered questionnaires for pregnant women who visited ELENA healthcare centers in May 2021., Results: Of 223 patients, 38% were smokers before pregnancy and 16% continued to smoke during pregnancy. Nearly all the smokers (98%) declared that they had reduced or stopped their tobacco use, mostly without help. Young age, lack of professional activity, an unfavourable reaction to the announcement of the pregnancy, heavy smoking before the pregnancy and the presence of a smoker spouse were associated with smoking during pregnancy. Our study identified 10% of vapers before pregnancy and 7.2% during pregnancy. Of those who vaped during pregnancy, 81% were smokers before pregnancy. Most of them used a nicotine containing liquid and 38% of vapers combined smoking and e-cigarettes during pregnancy. There was no association between vaping during pregnancy and smoking cessation. A minority of women had received information about smoking during pregnancy., Conclusions: The use of electronic cigarettes by pregnant women is a poorly-known reality in France, yet it concerns approximately 7% of the women in our sample. Prospective studies on larger numbers are needed to assess the prevalence of vaping among French pregnant women and its evolution during pregnancy., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction : Longitudinal studies make it possible to study the evolution of a class of individuals over time. However, they are rarely used in France to observe the same population of young adolescents according to their grade level over the course of several years.Purpose of research : Based on the longitudinal monitoring of repeated annual cross-sectional studies on young adolescents (from 15 to 18 years old) conducted at the Honoré d’Urfé public high school (Saint-Étienne, Loire, France) involving 336 10th grade pupils in 2018, 360 11th grade pupils in 2019 and 273 12th grade pupils in 2020, we observed and studied students’ smoking and vaping behavior over a period of three years.Results : Between the ages of 15 and 18 years, the prevalence of tobacco experimentation increased almost linearly (39.10%, 47.50%, and 53.11%), while the prevalence of ‘non-smoking’ decreased by 4.5%. In addition, the prevalence of e-cigarette experimentation was stable (46.38%, 49.44%, 47.62%), whereas the prevalence of daily vaping increased by 5.0%.Conclusions : The prevalence of tobacco experimentation tends to increase with age and to catch up with that of e-cigarette experimentation, which remains stable at this stage of adolescence. Introductions to these two products seem to be rather recreational, playful, and experimental in nature, and do not have a significant connection with the development of their daily use or propensity to addiction.

Introduction: Use of a spacer device to optimize the delivery of fluticasone to infants with asthma is an important issue and clinicians require guidance around the choice of device. This in vitro study characterizes the particle size and the fluticasone delivery via 9 spacers., Methods: We used an in vitro infant nasal cast with two different inspiratory flow rates (50 and 100mL/s). Fluticasone particle size in the aerosol was evaluated by laser diffractometry and tracheal deposition by spectrophotometric assay., Results: Significant differences in particle size were observed between the 9 spacers (similar D50 but D90 from 5.65±0.65 to 8.80±1.35μm). A 75 % or higher respirable fraction was obtained for only 5 spacers. The 50mL/s flow rate lead to the best drug delivery. At this flow, OptiChamber ® (62±3 %) and Vortex ® (91±8.5 %) had a tracheal deposition over 50 % of the initial dose of fluticasone, although the 7 other spacers exhibited a fluticasone deposition less than 25 %., Discussion: This study shows a wide variation of drug delivery between the 9 spacers studied. We demonstrate that a low inspiratory flow and a spacer showing antistatic properties facilitate drug delivery., (Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Study: The aim of our study was to study therapeutic results after thyroidectomy in patients positive for predictive genetic analysis and with preoperative calcitonin (CT) response to pentagastlin (Pg) < 150 pg/ml., Material and Methods: 36 patients (13 F, 23 M) were selected: 13 F-MTC from 8 families, 22 MEN 2A from 15 families and 1 MEN 2B. They were positive for direct RET mutation analysis. CT was assayed by immunoradiometric method before and after Pg. Pg test results before and after thyroidectomy, age at operation and histologic results were analysed., Results: Mean preoperative peak CT was 82.5 +/- 34.0 pg/ml (22-133): among these 36 patients preoperative basal and peak CT were normal in 16 and 2 patients respectively. F-MTC and MEN 2A patients were different according to their preoperative peak CT levels (58.1 +/- 24.0 vs 97.6 +/- 31.3) pg/ml, p < 0.01) and age at thyroidectomy (20.4 +/- 10.5 vs 11.6 +/- 7.6 years, p < 0.01 by Mann-Whitney test). Total thyroidectomy was performed in all patients at a mean age of 14.8 +/- 9.8 years (2.5-41.7) and was associated with lymph node dissection in 30 cases. The 2 F-MTC patients with normal preoperative peak CT levels had bilateral C-cell hyperplasia (CCH) associated with uni or bilateral micro-MTC. Other patients had uni or bilateral micro MTC except 4 who had isolated CCH without carcinoma. The age of two MEN-2A and 1 MEN 2B patients with micro-MTC ranged from 2.5 to 4.7 yr. Micro MTC was present in 100% of MEN-2A cases after the age of 10 yr. There were no lymph nodes metastases. During postoperative survey, the last PG tests (n = 33) were performed 27.5 months (1-92) after thyroidectomy: peak CT values were always < 10 pg/ml., In Conclusion: Thyroidectomy should be performed at a very young age in RET mutation carriers, regardless of the plasma CT values. This choice is justified in NEM-2A and NEM-2B patients but must be discussed in F-MTC families with less aggressive forms of the disease.

Perfused non working isolated rat heart preparations have been used to study whether alanine (0,89 gl-1) could represent an energy source for the myocardium. Its influence on glucose and lactate metabolism in the heart was also studied. The use of 14C labelled compounds permitted the estimation of the oxidation rate of these three metabolites. The results show that: 1) Alanine was not utilized by the heart. 2) Alanine did not alter myocardial glucose metabolism or lactate oxidation. 3) Alanine lowered lactate uptake by the myocardium which may indicate that alanine influences lactate transport through the cell membranes. One may speculate that in vivo, alanine will not interfere with glucose or lactate metabolism by the heart as, even in acute physiological conditions (exercice, hypoxie, fasting) lactate is always present in blood at higher concentration than alanine.

The simultaneous utilization of carbohydrates and amino acids in the metabolic response to oxygen deprivation was studied i the isolated rat heart initially perfused according to Langendorff and submitted to periods of 2, 5, 10 and 15 min of complete ischemia. The results of the measurement of metabolite contents showed : (1) an immediate decrease of glycogen, pyruvate, alpha-ketoglutarate and aspartate; (2) a delayed decrease of citrate and glutamate; (3) an immediate and continuous increase of lactate and succinate; (4) a delayed increase of alanine; (5) a transient increase of malate + fumarate. The end products of anaerobic metabolism are lactate, which is an index of glycolytic activity, and alanine and succinate, which are indexes of amino acid fermentation. Succinate originates from aspartate, and alanine originates from glutamate. The amino acid pathway does not seem of importance in the production of ATP compared to glycolysis. However, its eventual role and the physiological implication of these reactions in the resistance of strict aerobic organisms to oxygen deprivation are discussed.

Blood alanine (Ala), an important glucose precursor, has been demonstrated to result mainly from the transamination of pyruvate derived from glucose in muscle [10]. A positive relationship between blood pyruvate and blood alanine was reported during muscular exercise and fasting. The alanine/pyruvate relationship in arterial blood has been studied in male fasted anesthetized rabbits before, during and after a short term hypoxic stress (50 minutes). Three groups of animals were studied : normoxic control (FIO2 = 0.28 ; n = 3) (C), hypoxic hypoxia (FIO2 = 0.10 ; n = 4) (HH) and hypoxia induced by respiring the animals with a carbon monoxide containing gas mixture (FIO2 = 0.28, FICO = 0.002 ; n = 6) (HCO). The hypoxic stress was of similar magnitude in HH and HCO groups. During the hypoxic periods an increase of [Ala] was observed along with hyperlactatemia and hyperpyruvatemia. Hyperalaninemia and hyperlactatemia was higher in HH than in HCO groups and hyperglycemia was observed only in HH group (adrenergic stimulation). In normoxic conditions [Ala] correlates positively with pyruvate. This relationship vanishes during the hypoxic and post hypoxic periods. The percentage increase of [Ala] during hypoxia was larger than that of pyruvate. These data, as well as recent reports in the literature, suggest that elevated [Ala] during hypoxia may result from increased muscular production from glycolytic pyruvate and other amino acids and decreased hepatic utilization (gluconeogenesis).

Postpartum thyroiditis. 31 cases. Between 1977 and 1986, 29 women consulted in three internal medicine and endocrinology departments for clinical disorders which could be ascribed to 31 episodes of thyroiditis developed within 9 months of giving birth. Thyroiditis was diagnosed clinically on the basis of acute diffuse (11 cases) or nodular (7 cases) goitre formation, signs of dysthyroidism (16 cases) revealed by menstrual disturbances and/or galactorrhoea (11 cases). A thyrotoxic episode was observed in 9 patients; it was either without sequelae (5 cases) of followed by transient hypothyroidism (4 cases). In other patients transient hypothyroidism was observed in 11 cases and permanent hypothyroidism in 5 cases. Six patients showed no sign of dysthyroidism, and the diagnosis was made by immunological, cytological and/or histological examination of the thyroid gland. Circulating anti-thyroid antibodies were present in two-thirds of the patients. The results of radioisotope scanning varied according to the stage of the disease. In these patients, only the absence of goitre was predictive, in 4 out of 5 cases, of subsequent permanent hypothyroidism; in all other patients the prognosis was highly favourable, even without specific treatment.

The study was designed to measure sequential changes in plasma renin activity, aldosterone, angiotensin-converting enzyme activity and ionograms, prior to, and after therapeutic plasma exchange. Each measurement was repeated before and after stimulation of renin activity induced by furosemide. The results showed that plasma exchange induces a syndrome of hyperreninemic hypoaldosteronism associated with a depletion in angiotensin-converting enzyme activity which might account for the dissociation between plasma renin activity and aldosterone.

The density of normal red blood cells increases during their 3-month life span. This characteristic has been used for many years to separate younger from older cells by centrifugation, allowing biochemical and physiological studies on the ageing process in red cells to be performed. The methods which have been proposed to date using discontinuous density gradients made of high density chemical compounds required high speed centrifugation of long duration. These gradients with pre-established density layers are well designed to separate red cells when their density varies over a small range as in blood from healthy donors. Pathological red cells such as found in sickle cell anaemia, thalassaemia syndromes or haemolytic anaemia of various origins display a wide and unpredictable range of densities which precludes the use of a standard discontinuous gradient. Because the fractionation of such pathological blood specimens is of great clinical and biochemical interest we report the details of a new method which combines two steps: firstly and analytical method performed with phthalate esters which allows estimation of the distribution of particular red cells, secondly a preparative method using Percoll solutions to prepare the discontinuous density gradient according to the histogram given by the first step. Two examples are described illustrating this interesting method which may possibly be applied to other blood disorders.

The increased tolerance to O2 deprivation of the myocardium after physical training was studied using the isolated working heart preparation and rats moderately trained by swimming. Glycolytic utilization of exogenous glucose and lactate production were determined under oxygenated conditions (Po2 # 500 Torr, 10 min), during severe hypoxia (P02 less than 50 Torr, 10 min) and during post-hypoxic perfusion (Po2 # 500 Torr, 15 min). The energetic state (CP, ATP, ADP, AMP) and glycogen store were determined at the end of the experimental procedure. The beneficial effect of training was evidenced by the restoration of aortic flow in the post-hypoxic period in hearts from trained animals (CE), whereas it did not return to the prehypoxic level in hearts from sedentary animals (CS). The increase in glycolytic utilization of exogenous glucose during hypoxia (x 2.5) was not very different in CE and CS, whereas lactate production was higher (+ 50%) and of longer duration in CE than in CS, This higher lactate production was the consequence of the larger glycogen store in CE than in CS. Moreover, glycogen resynthesis during the post-hypoxic period was higher in CE than in CS. Thus, a changed glycogen metabolism, and also higher CP and ATP contents in CE compared to CS, are examples of metabolic events implicated in the increased tolerance to O2 deprivation of the myocardium induced by physical training.

The purpose of the present report is to review current knowledge on amino-acid metabolism during hypoxia in vivo and in vivo, mainly in the myocardium. We have first considered biochemical events occurring in muscles during anoxia either in facultative anaerobic invertebrates or in aerobic vertebrates. In the invertebrate muscle, simultaneous utilization of carbohydrate and amino acids in anoxia leads to ATP formation and accumulation of CO2, alanine and succinate. In aerobic species, ATP production in anoxic conditions is mostly or totally derived from glycolysis, lactate being the end product. Recent studies from various authors have suggested that amino acid utilization may be present in aerobic species exposed to hypoxia and contribute to energy production under these conditions. Experiments using the isolated rat heart preparation have demonstrated the accumulation of alanine and succinate in addition to that of lactate during short period of hypoxia (Fig. 8). The relative importance of these biochemical events in term of energy production is discussed. It is also postulated that the accumulation of alanine and succinate in the myocardium during hypoxia may be involved in other physiological processes.