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Biomedical subjects

G Touati

Publications and source records attributed to G Touati.

At least 55 records · Page 3Linked to original sources
PubMed1998

Long-term treatment of persistent hyperinsulinaemic hypoglycaemia of infancy with diazoxide: a retrospective review of 77 cases and analysis of efficacy-predicting criteria.

UNLABELLED: Primary persistent hyperinsulinaemic hypoglycaemia of infancy is rare. Diazoxide treatment remains the mainstay of medical therapy in long-term management. We reviewed 77 cases of primary persistent hyperinsulinism in neonates and infants who were treated with diazoxide and studied criteria predictive of therapeutic efficacy. The only criterion identified was age at manifestation. All but 1 of the 31 neonatal cases were unresponsive to diazoxide. Responsiveness increased with age: 12 of 39 early-infantile cases, and all seven late-infantile cases were diazoxide-responsive. In responders, a diazoxide dose of 10-15 mg/kg per day was always effective, suggesting an "all or none" response. Diazoxide-resistant hyperinsulinism is characterized by its severity with higher plasma insulin levels. The analysis of 46 surgically treated patients showed that the efficacy of diazoxide is not related to the aetiology of the pancreatic lesions. In six cases, after many years of management, diazoxide treatment was stopped without recurrence of hypoglycaemia. CONCLUSION: Diazoxide is an efficient treatment in the long-term management of most persistent hyperinsulinaemic hypoglycaemia of infancy revealed in infants and children but is usually ineffective in neonatal forms. Drug efficacy does not correlate with anatomical lesions. Medical treatment can sometimes be stopped after many years of management without recurrence of disease manifestations.

Diazoxide↗
PubMed1998

[Persistent hyperinsulinemic hypoglycemia in the newborn and infants].

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.

Diazoxide↗
PubMed1998

Exploration of glucose homeostasis during fasting in growth hormone-deficient children.

In order to define more precisely the risk of hypoglycaemia in GH-deficient children and to clarify the role of growth hormone (GH) in glucose homeostasis, a 24-h fast was monitored in 10 GH-deficient children aged 1.1-6.5 y. Asymptomatic hypoglycaemia (blood glucose < or = 2.6 mmol/l) occurred in 9/10 children, 2 of whom prematurely interrupted the test. Blood glucose profile was not reproducible between children and had no correlation with age (p = 0.48). Gluconeogenesis was considered as non-altered as read from the normal plasma lactate and pyruvate concentrations throughout the test. Plasma ketone body concentrations increased during the test, but were lower than expected with respect to the decrease of blood glucose. This suggests insufficient ketogenesis which could exacerbate hypoglycaemia in GH-deficient children if brain glucose utilization were not alleviated by ketone body oxidization, as is normally the case. The positive glucose response after glucagon stimulation in 6/10 patients indicated normal hepatic glycogen content. However, these responses were unexpected following the prolonged fast and its concomitant hypoglycaemia, and would therefore tend to suggest a defect in glycogenolysis. These results confirm the tendency to hypoglycaemia, even after infancy, in GH-deficient children. These hypoglycaemias may occur by different types of malfunctioning, such as insufficient ketogenesis or a defect in glycogenolysis. These hypotheses require confirmation by a more systematic study of the metabolic and hormonal changes that occur during fasting in both GH-deficient and normal children.

Blood Glucose↗
PubMed1998

Beneficial effects of one-year growth hormone administration to children with juvenile chronic arthritis on chronic steroid therapy. I. Effects on growth velocity and body composition.

Severe growth retardation and profoundly altered body composition are observed in children with systemic forms of juvenile chronic arthritis receiving glucocorticoids. The purpose of this study was to assess the effects of recombinant human GH (rhGH) on growth velocity (GV) and body composition studied by dual-energy X-ray absorptiometry, during a 1-yr treatment course, together with potential adverse effects on glucose tolerance. Fourteen patients were treated with rhGH (1.4 U/kg per week) for 1 yr and were then studied for a 2nd yr off GH. Baseline GH secretion, GH binding protein (BP), insulin-like growth factor-I (IGF-I), and IGFBP3 levels were at the lower limit of normal. The rhGH treatment increased IGF-I and IGFBP3 plasma levels to above-normal values. All patients showed an increase in GV, and mean GV increased from 1.9-5.4 cm/yr (P < 0.001). Compared with the value on day 0, lean body mass increased by 12.2% (P < 0.01), and the fat mass excess fell by 19.5% (P < 0.01). Decreased glucose tolerance (as determined by oral glucose tolerance test) and increased glycosylated hemoglobin levels were observed during treatment. This effect may be attributed to insulin resistance, as reflected by induced hyperinsulinemia. Eleven children were monitored for 1 yr after the cessation of GH therapy. GV fell to pretreatment values, whereas height in SD score at the end of the 2nd yr was lower (P < 0.01) than before treatment. Weight and fat mass again increased markedly. Although long-term controlled studies are needed to assess the risks and benefits of GH therapy in this setting, our results suggest that rhGH may partially counteract the adverse effects of glucocorticoids on growth and metabolism in patients with chronic inflammatory disease.

Absorptiometry, Photon↗
PubMed1997

Intrapericardial fibrinolysis: a useful treatment in the management of purulent pericarditis.

Since the introduction of antibiotics into clinical practice, purulent pericarditis has become a rare disease. The major complication of the standard management for this condition is constrictive pericarditis. We report two cases of purulent pericarditis in which intrapericardial fibrinolysis was performed in order to minimize this complication. The first case was a 38-year-old man admitted to our intensive care unit (ICU) for management of constrictive pericarditis complicating purulent pericarditis diagnosed 17 days previously. The patient was treated with four intrapericardial injections of streptokinase (250,000 IU each). Fluid drainage and cardiac output were improved. No change in clotting parameters was noted. Pericardiectomy and esophagectomy were then performed for a diagnosis of esophageal neoplasm. The postoperative course was uneventful. The second case was a 16-year-old boy admitted with loss of consciousness due to cardiac tamponade. Percutaneous pericardiocentesis drained 900 ml of cloudy fluid. Two intrapericardial injections were performed (day 1 and day 5) without any complication. Pericardial drainage was withdrawn on day 13 and the patient was discharged from ICU on the same day. Six months later, there was no evidence of constrictive pericarditis. Intrapericardial fibrinolysis appears to be safe and effective when prescribed rapidly in the course of purulent pericarditis.

Adolescent↗
PubMed1997

A thyroxine dosage of 8 micrograms/kg per day is appropriate for the initial treatment of the majority of infants with congenital hypothyroidism.

UNLABELLED: The adequate L-thyroxine dosage for the initial treatment of infants with congenital hypothyroidism is a subject of controversy. Some recommend higher dosages (> 10 micrograms/kg/day) to ensure adequate levels, while others advocate lower dosages to permit normalisation of thyroid status. The aim of this study was to evaluate the results of a treatment strategy using an initial dosage of 7.5-8.0 micrograms/kg per day, TSH measurements being taken at 15 and 30 days of treatment. Fifty one newborns infants with primary congenital hypothyroidism detected by neonatal screening were treated with the same therapeutic strategy. A mean L-thyroxine dosage of 7.9 micrograms/kg per day at the onset of treatment and 6.6 micrograms/kg/d at 2 months, normalised the FT4 and FT3 levels at 15 days in 100% and TSH levels at 2 months in 90% of cases. Many patients showed elevated levels of FT4 and a systematic higher initial dosage could expose many infants to a dangerous hyperthyroidism. Patients with abnormal TSH levels at 2 months already had higher TSH levels in the first 8 weeks of life and, despite higher L-thyroxine dosage, also exhibited lower FT4 and FT3 levels. These patients who needed an early increase in dosage had already shown a more profound ante and neonatal hypothyroidism. This subgroup of patients require a higher dosage of thyroxine and early assessment of FT4, FT3 and TSH levels are required for optimum dosage choice. CONCLUSION: Even though a subgroup of patients may require a higher dosage of L-thyroxine, an initial dosage of 7.5-8.0 micrograms/kg per day, with an early assessment of FT4, FT3, and TSH levels, is adequate for the treatment of the majority of infants with congenital hypothyroidism.

Congenital Hypothyroidism↗
PubMed1997

In vivo functional investigations of lactic acid in patients with respiratory chain disorders.

OBJECTIVE: To assess the prevalence of in vivo detectable abnormalities of lactate metabolism in mitochondrial disorders. DESIGN: Retrospective study in a metabolic investigation unit. PATIENTS: 28 patients with a respiratory chain disorder identified from biochemical or genetic analyses, or both, and 133 age matched controls. Controls were children in whom causes of secondary hyperlactataemia and/or disorders, affecting the energy pathways could be excluded. METHODS: Lactate and pyruvate were measured in blood, together with other intermediary metabolism indices, before and one hour after four meals each day. Lactate and creatinine in a 24 hour urine sample collected at the same time were analysed. When basal hyperlactataemia was not evident, an intravenous glucose or pyruvate loading test was performed as a provocative test. RESULTS: Abnormal lactate metabolism was found in 25 of 28 patients thus demonstrating the potential usefulness of these investigations in the diagnosis of mitochondrial disease. Moderate lactate accumulation was present in relatively mild disease, associated with a mitochondrial DNA mutation and combined respiratory complexes deficiency. By contrast, high lactate concentrations were observed in very young children, with severe disease, isolated complex deficiency, and no apparent mitochondrial DNA defect.

Adolescent↗
PubMed1996

Morphological studies of skeletal muscle in lactic acidosis.

This paper underscores the contribution of routine morphological examination of skeletal muscle in patients with lactic acidosis. Mitochondrial disorders are by far the most common causes of primary lactic acidosis, in which muscle biopsy analysis helps in diagnosis and in the search for the molecular anomalies. Thus, we focus our attention on one particular point: the contribution of the morphological study of muscle biopsy in primary lactic acidosis due to mitochondrial disorders, especially mitochondrial respiratory-chain diseases.

Acidosis, Lactic↗
PubMed1996

Clinical and molecular heterogeneity of cytochrome c oxidase deficiency in the newborn.

We report 8 cases of severe cytochrome c oxidase deficiency with onset in the neonatal period. Clinical symptoms were heterogeneous: antenatal cerebral malformations, neurological distress with ketoacidosis, severe myopathy, or isolated respiratory control failure. Lactic acid was elevated in blood and/or CSF in 7 cases. Muscle biopsy (7 patients), liver biopsy (4 patients), and cultured skin fibroblasts (7 patients) were used to assess the cytochrome c oxidase deficiency. Among the patients, the enzymatic defect differed in the level of residual activity, expression in different tissues and subunit composition in muscle (as analysed by immunohistochemistry). Southern blot analysis of the mitochondrial DNA was normal in 7 patients. The heterogeneity of cytochrome c oxidase deficiency was therefore demonstrated by these clinical presentations and by the biochemical assessment of the enzyme defect. This reflects, most probably, the diverse nature of the causal mutations.

Cytochrome-c Oxidase Deficiency↗
PubMed1996

[Lysinuric dibasic protein intolerance: characteristic aspects of bone marrow involvement].

BACKGROUND: The marrows of patients with lysinuric protein intolerance (LPI) are generally considered as normal, even though autoerythrophagocytosis has been observed in some of them. CASE REPORTS: Lysinuric protein intolerance was recognized in two 12 and 15-year-old brothers who had been diagnosed following an immuno-hematological investigation. Clinical history had been characterized by a neonatal macrophage activation syndrome (hepatosplenomegaly, pancytopenia, hypofibrinogenemia and hypertriglyceridemia). A putative diagnosis of familial lymphohistiocytosis had been ruled out because of unusual clinical and immunological course. Both brothers had displayed chronic aversion to high-protein foods, failure to thrive, osteoporosis and developmental delay. Metabolic investigations had revealed chronic hyperammonemia while cationic aminoaciduria (lysine, arginine and ornithine) was only present during L-citrulline supplementation. Bone marrow examinations had been performed during the neonatal period and during later metabolic investigations. They both displayed a peculiar red cell and granulocytes phagocytosis by histiocytes and granulocytes precursors. CONCLUSIONS: This aspect of bone marrow could be considered as a specific sign of LPI. This report suggests that appropriate metabolic investigations should be performed in any unexplained macrophage activation syndrome.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

Hyperinsulinism in children: diagnostic value of pancreatic venous sampling correlated with clinical, pathological and surgical outcome in 25 cases.

Neonatal hypoglycemia represents an emergency of heterogeneous etiology. The occurrence of persistent hypoglycemia caused by hyperinsulinism has not been well established. Some authors claim that it may be more common than previously suggested. The diagnostic goal is to distinguish hyperinsulinemia from other causes of hypoglycemia because management strategies differ. The diagnosis of persistent hypoglycemia attributable to hyperinsulinism is made when insulin secretion is excessive or inappropriate (> 10 microIU/ml). Medical management includes frequent feeding, high hydrocarbon intake, glucagon, diazoxide, somatostatin or steroid treatment. In case of resistance to medical intervention, surgery consisting of subtotal pancreatectomy is performed to avoid neurological sequelae. However, pediatric organic hypoglycemia secondary to hyperinsulinism can be caused by either diffuse or focal pancreatic lesions. Differentiation between these two types of lesion is necessary since partial pancreatectomy can prevent diabetes. In this prospective study, pancreatic venous sampling (PVS) was evaluated for the preoperative localization of lesions in 25 children with hyperinsulinism and correlated with surgical, pathological and clinical outcome. PVS is the most accurate preoperative technique for localizing focal lesions in children. Besides being safe and effective, it has the great advantage of detecting focal secretion, thus reducing the need for extensive surgery.

Adolescent↗
PubMed1995

Neonatal hyperammonemia caused by a defect of carnitine-acylcarnitine translocase.

Carnitine-acylcarnitine translocase deficiency is a newly recognized inborn error of metabolism that involves transport of long-chain fatty acids into mitochondria, which in turn impairs mitochondrial beta-oxidation, and ketogenesis. We report a new familial example; the affected twins had neonatal distress, hyperammonemia, and transient intracardiac conduction defects. Clinical and biochemical analysis of both our patients and the two previously reported patients revealed that this inherited defect could be manifested during the neonatal period without any of the signs classically associated with fatty oxidation defects. In contrast, all four patients had sustained and "isolated" hyperammonemia, which could be misinterpreted as being caused by urea cycle defects. We conclude that carnitine-acylcarnitine translocase deficiency is a potential differential diagnosis in neonates with unexplained neonatal hyperammonemia. Cardiac and muscle involvement may represent further early pivotal symptoms.

Ammonia↗
PubMed1992

[Current role of reconstructive surgery in the treatment of acute mediastinitis after cardiac surgery].

Infected median sternotomy often requires wide debridement. A large thoracic defect usually results with subsequent exposition of heart, great vessels, aortocoronary bypass grafting, vascular prosthesis. Coverage with muscles transplantation was the standard procedure carried out in this series of 150 cases observed between 1983 and 1991. Details of technique are presented as well as a review of our reconstructive options. Rewarding results were observed even in the most challenging circumstances, suggesting that pursuing this aggressive approach was warranted.

Acute Disease↗
PubMed1990

[Coronary artery bypass with bovine internal mammary artery graft].

Ten of 1,025 patients undergoing coronary bypass surgery received one or two bovine internal mammary artery grafts. Surgery consisted in quadruple coronary bypass in 1 case, triple coronary bypass in 3 cases and double coronary bypass in 6 cases using 4 autologous saphenous vein grafts, 6 autologous internal mammary artery grafts and 13 bovine internal mammary artery grafts. It was necessary to use bovine internal mammary artery grafts because of total bilateral venous stripping in 5 patients, diffuse, bilateral varicose veins in 4 patients and because of the insufficient length of the vein in 1 patient. Short and medium-term (12 months) angiographic studies of the bovine grafts showed 5 occluded grafts, 2 proximal graft stenoses, and 1 patient graft up to the time of his death of extracardiac causes, with a maximum follow-up of 13 months. One of these 10 patients died in the early postoperative period of extracardiac causes with a patent bovine coronary graft. Another patient died in the 5th postoperative month during reoperation motivated by occlusion of the two implanted bovine coronary grafts. The other 8 patients are alive and stable from the coronary view point. Bovine internal mammary artery grafts may be used to manage an acute episode of coronary insufficiency by providing the time for the collateral circulation to develop but it does not provide a complete and durable method of revascularisation. Their use should therefore be reserved for exceptional cases.

Aged↗
PubMed1990

[Coronary artery bypass using bovine internal mammary artery].

Among 760 patients who underwent coronary artery bypass graft (CABG) 8 received one or two bovine internal mammary artery grafts. The surgical procedures were 4, 3 and 3 CABG respectively in 1, 3 and 4 cases with greater saphenous veins in 4 cases, internal mammary artery in 4 cases and bovine internal mammary artery in 11 cases. The 3 mm bioflow grafts were used to revascularize the left coronary artery in 6 cases (to the left anterior descending, circumflex artery) and the right coronary artery in 5 cases. The indications for the use of bovine mammary artery grafts were lack of suitable autologous vessels because of bilateral saphenous vein stripping in 4 cases, bilateral varicose veins in 3 cases and inadequate length of vein in 1 case. Post-operative angiographic studies of these bovine mammary grafts with a maximum follow-up of 11 months showed 5 occluded grafts, 2 grafts with proximal stenosis, one graft which remained patent until the patient died and 3 grafts still under evaluation. Bovine internal mammary artery grafts provide a solution for the acute stage of coronary disease, but do not achieve total and durable revascularization. Their use must remain exceptional.

Aged↗
PubMed1990

[Heart tumors in newborn infants and infants. Apropos of 5 cases].

Between February 1985 and March 1987, 5 children underwent resection of primary cardiac neoplasms, 3 of them in the first days of life and 2 before the age of 6 months. Routine echocardiographic follow-up of pregnancies allowed detection of cardiac tumors in 2 foetuses 30 and 36 weeks old. In 3 children the diagnosis was suspected by the discovery of cardiac murmur or congestive heart failure. The first case was an hemangioma, originating from outside of the left ventricular wall, which could be resected without cardiopulmonary bypass (CPBP). The other case was a pseudomyxoma, spreading extensively inside the right atrium. The third case was a rhabdomyoma arising from the pulmonary infundibulum with clinical manifestations of tuberous sclerosis. The last two patients had intraseptal lesions, just above the aortic valve; complete resection was therefore impossible, particularly in one patient with multiple tumors. There was one death related to congestive heart failure. The remaining four survivors were followed up for an average of 18.4 months (+/- 12.9) and all were in functional class I. Echocardiographic follow-up showed evidence of a residual subaortic lesion in one asymptomatic patient.

Age Factors↗