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Biomedical subjects

S Halimi

Publications and source records attributed to S Halimi.

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

[Benefits of blood glucose self-monitoring in the management of insulin-dependent (IDDM) and non-insulin-dependent diabetes (NIDDM). Analysis of the literature: mixed results].

Since the 1980s, self-monitoring of blood glucose (SMBG) has allowed easier and improved treatment of insulin-dependent diabetes mellitus (IDDM). SMBG has proved efficient in very selected patients and in conditions such as pregnancy, intensive insulin therapy (CSII and optimal bolus regimen), physical exercise and self-awareness of specific hypoglycaemic symptoms. Through the use of pen insulin injectors, SMBG should improve the autonomy, well-being and metabolic control of most IDDM patients. However, as SMBG is continuing to develop in France, costs are rising (estimated at $170 million per year in 1997), which has led some diabetologists to question its real benefit for all diabetic patients and its cost-effectiveness. Our study of published data indicates that SMBG often fails to be beneficial in non-selected IDDM patients, whether children adolescents or adults. However, educational sessions on SMBG and insulin dose adjustment have demonstrated that SMBG improves well-trained patients. Most authors recommend applying psychosocial scales and suitable educational tools to obtain positive results and justify the human and economic costs involved. In non-insulin-dependent diabetes mellitus (NIDDM), the use of SMBG is increasingly recommended by diabetologists and general practitioners. However, trials investigating the effects of SMBG in NIDDM patients have found no benefit for metabolic control or weight loss. We recommend a moderate use of SMBG in NIDDM patients and the development of clinical research strategies to study the benefit for NIDDM patients of a method which is increasing health costs appreciably.

Blood Glucose Self-Monitoring↗
PubMed1997

Standardization of procedure for efficient ex vivo gene transfer into porcine pancreatic islets with cationic liposomes.

BACKGROUND: New strategies to improve the outcome of encapsulated porcine islet transplantation may involve the transfer of gene sequences affecting islet viability. While adenoviral vectors appear as the most efficient gene transfer system so far established for islets, non-viral-based vectors are most likely to fulfill microbiological safety criteria and be retained in the clinical setting. Our aim was to standardize the procedures of gene transfer into adult porcine islets using cationic liposome DOTAP. METHODS: Porcine islets obtained by collagenase digestion and density gradient purification were lipofected with plasmids coding for luciferase or beta-galactosidase under the control of simian virus 40 or cytomegalovirus promoter. The following parameters were explored: exposure time to vector (1-48 hr), DNA amount (1-15 microg/500 islets), and DOTAP to DNA ratio (2-16). Reporter gene expression was determined 48-72 hr after lipofection. RESULTS: Efficiency and reproducibility of transfection were maximal with the following procedure: 3-hr exposure time followed by islet washing, 12 microg of DNA per 500 islets (150 microm equivalent), and DOTAP to DNA ratio of 12 microl/microg. Freshly isolated islets in large aliquots (n=4000 in 50-ml tubes) were efficiently transduced with this procedure, and distribution of gene expression was homogenous when islets were subsequently plated in 500-islet aliquots. Luciferase gene expression was detected for a minimum of 7 days after lipofection. Gene expression was also evident up to 4 weeks after islet transplantation beneath the kidney capsule of athymic mice. Transfection of islets using the beta-galactosidase vector yielded 25% positive islets. Islet viability was not adversely affected. CONCLUSIONS: This islet lipofection procedure may help achieve the local release of a bioactive peptide in the graft environment and have therapeutic applications in islet transplantation.

Animals↗
PubMed1997

Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.

Adult↗
PubMed1997

Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets.

The purpose of this study was to investigate the effects of vitamin E in rats fed a high fructose diet which leads to insulin resistance, on some components of the free radical defense system and on insulin sensitivity. The rats (postweaning, 50 g) were divided into three groups: the control group (C, n = 16), which received a purified diet containing 60 g/100 g carbohydrates, the high fructose-fed group (FT, n = 16),fed a diet in which 56.8% of the carbohydrate as fructose, and a high fructose and vitamin E-fed group (FVE, n = 16), fed the FT diet supplemented with 3.4 g vitamin E/kg diet (vs. 0.17 g/kg in C and FT groups). The duration of the treatment was 6 wk. Insulin sensitivity was determined in half of the rats in each group using the euglycemic hyperinsulinic glucose clamp technique. The remaining rats were investigated for plasma glucose, insulin, triglyceride and fructosamine concentrations and for components of the free radical defense system. The FT group had a significantly lower insulin sensitivity than the C group. Basal glycemia was not different among the groups. In comparison with the C group, the FT group had a greater lipid peroxidation, as indicated by the higher concentrations of plasma thiobarbituric acid reactive substances (TBARS) and blood disulfide glutathione (GSSG) and the lower Cu-Zn superoxide dismutase (Cu-Zn SOD) activity. These markers approached the values of the controls after addition of vitamin E. Moreover, the FVE group had a higher insulin sensitivity than the FT group, but it remained lower than in the C group. These results show that a high fructose diet in rats leads to insulin resistance and a defect in the free radical defense system. Vitamin E supplementation improves insulin sensitivity in fructose-fed rats.

Animals↗
PubMed1995

Effects of ritanserin, a specific serotonin-S2 receptor antagonist, on the release of anterior pituitary hormones during insulin-induced hypoglycemia in normal humans.

The role of serotonin in the insulin hypoglycemia (IH) stimulated secretion of prolactin (PRL), growth hormone (GH), adrenocorticotropin (ACTH) and cortisol (F) was studied in a group of 12 normal subjects during the control period after placebo and a consecutive six-day treatment with 20 mg ritanserin (RIT) per day. RIT failed to affect the baseline levels of all the four hormones as well as the PRL response to IH (p > 0.5). The serum GH response to IH was moderately diminished after RIT, the reduction of integrated trapezoidal area under hormone curves (nAUC) being 50.7% +/- 6.9% (p < 0.005). Furthermore, RIT was found to slightly decrease the plasma ACTH response to IH, the reduction of nAUC being 36.3% +/- 2.6% (p < 0.005). Decrease in the corresponding plasma F response to IH was accompanied by 29.1% +/- 2.4% reduction of nAUC (p < 0.005). According to our results, serotonin-S2 receptors appeared to be moderately involved in IH-induced release of GH, but slightly in that of ACTH, leaving unaffected that of PRL.

Adult↗
PubMed1995

Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: effects of an oral zinc supplementation.

DESIGN: Placebo for 3 months, followed by 30 mg/day zinc gluconate in identical capsules. SETTING: Diabetic out patients clinic at the University Hospital, Grenoble. SUBJECTS: Diabetic patients cared for type I diabetes mellitus. 22 patients began the study, 4 dropped out. 10 patients suffered of an early retinopathy, 8 patients had no retinopathy. INTERVENTIONS: In this order: T0 biological measurements, 3 months placebo treatment, T1 biological measurements, 3 months zinc gluconate treatment, T2 biological measurements. Plasma Zn, Cu, Se, thiobarbituric acid reactants and antioxidant enzymes were measured [plasma and red glutathione peroxidase (Se-GPx), red cell superoxide dismutase (Cu-Zn-SOD)]. RESULTS: Lower plasma zinc level in the two groups. An increase in zinc level was observed and was more important in diabetic patients with no retinopathy (P = 0.05). The thiobarbituric acid reactants were above the reference values in all the patients, and were decreased at T2 (P < 0.05). Increase of GPx activity after zinc supplementation in patients with retinopathy. CONCLUSIONS: Zinc deficiency in insulin-dependent diabetic patients is corrected by a zinc supplementation. Moreover this supplementation decreases lipid peroxidation. The effects of zinc are different in diabetic patients with or without retinopathy. The increase in Se-GPx activity observed in patients with retinopathy could be linked to the protective effect of zinc on the protein itself.

Adult↗
PubMed1995

[Leg ulcer and Klinefelter syndrome].

We report a case of 47 years old patient who was admitted to hospital because of bilateral leg ulcers for 6 years. Chromosome analysis revealed XXY karyotype, confirming the clinical diagnosis of Klinefelter's syndrome. Testosterone level was low and Plasminogen Activator Inhibitor (PAI-1) was elevated. The patient was given androgen therapy which resulted in a normalization of the PAI-1 activity. The frequency of leg ulcers in patients with Klinefelter syndrome is between 6 and 12% according to studies. Different causes would explain the tendency towards leg ulcers in Klinefelter's syndrome: conjunctive tissues abnormalities were revealed in some studies. A higher frequency of venous insufficiency is reported in patients with Klinefelter's syndrome, either due to the particular morphology (obesity, taller size) or due to an androgen deficiency. A few arterial dysplasias cases of arteries's legs were described in patients with leg ulcers and Klinefelter syndrome. Haemostasis disorders presented in this case and normalized after androgen therapy will contribute to the physiopathologic discussion.

Adult↗
PubMed1994

Zinc prevents the structural and functional properties of free radical treated-insulin.

We have previously reported that zinc deficiency could increase in vivo lipid peroxidation and decrease rat insulin sensitivity. In the present paper, we address the hypothesis of the role of zinc on insulin molecule in relation to free radical damage. From native recombinant human insulin, we prepared a zinc-depleted insulin. Both preparations were subjected to controlled free radical attack by incubation in the presence of 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). To obtain minimally oxidized insulin, the oxidation process was monitored by measuring the intrinsic fluorescence of the insulin preparations. For 2.5 mM of AAPH, the autofluorescence of zinc-depleted insulin markedly decreased as compared to that of native insulin. These data are in favor of conformational changes of the insulin molecule which were further studied by quenching of fluorescence by means of potassium iodide. Using the euglycaemic hyperinsulinic glucose clamp technique in rats, the in vivo activities of the different insulin preparations, showed that oxidized zinc-depleted insulin had a marked reduced activity as compared to oxidized native insulin. From our results, we suggest that structural modification of the insulin molecule took place after zinc depletion and free radical treatment. Moreover, zinc depletion appeared to increase the susceptibility of insulin to free radicals.

Animals↗
PubMed1994

Effects of ritanserin, a novel serotonin-S2 receptor antagonist, on the secretion of pituitary hormones in normal humans.

The availability of a new potent and selective serotonin-S2 antagonist, ritanserin (RIT), encouraged us to further investigate the effect of serotonin on the basal secretion of anterior pituitary hormones in normal humans. Administered in a single 30-mg dose to group 1 consisting of 10 normal women, RIT failed to affect the baseline LH, FSH, GH or TSH levels. In group 2 consisting of 20 normal subjects (ten males and ten females), the same dose of RIT decreased in parallel both ACTH and cortisol levels but only at 180 min. Group 3 consisting of 8 normal men was studied on three separate occasions seven days apart: each subject received graded doses of 10 mg, 20 mg and 30 mg RIT. The mean baseline PRL concentration at 180 min as well as the net integrated area under the hormone curve (nAUC) decreased only after the highest dose, while the baseline cortisol concentrations at 180 min as well as the corresponding nAUC values displayed a clear dose-dependent response. The findings indicated the serotonin-S2 receptors to be only partially involved in the basal secretion of ACTH in normal humans.

Adolescent↗
PubMed1994

Measurement of salivary insulin-like growth factor-I in acromegaly: comparison with serum insulin-like growth factor-I and growth hormone concentrations.

The aim of this study was to establish the concentration of insulin-like growth factor-I (IGF-I) in saliva of acromegalic patients, and to compare it with the basal levels of serum IGF-I and growth hormone. IGF-I was determined in extracted serum or neat saliva by a disequilibrium RIA using antibodies and iodinated ligand from Amersham and WHO 87/518 as standard. The detection limit of the assay was 0.5 microgram/l, and the intra- and interassay coefficients of variations were 7.9% and 15% respectively. Our study included 13 healthy adult individuals and 17 acromegalics. Compared with healthy adult subjects, acromegalics had significantly higher salivary IGF-I concentrations (mean +/- SEM 5.4 +/- 2.64 vs. 10.5 + -5.69 micrograms/l; p < 0.01), as well as serum IGF-I (176 +/- 42.9 vs. 520 +/- 98.8 micrograms/l; p < 0.0001) and somatotropin levels (1.2 +/- 1.02 vs. 15.4 +/- 9.89 micrograms/l; p < 0.0001). However, 47.1% patients (8 out of 17) with active acromegaly had salivary IGF-I concentrations within the normal range. Serum IGF-I and somatotropin concentrations were found to follow more closely the disease activity after adenomectomy, compared with the concentrations of salivary IGF-I. These results suggest that the IGF-I levels in serum and saliva are somatotropin-dependent. According to our results, measurement of IGF-I in saliva cannot be considered as an additional measure for evaluation of the disease activity in acromegaly, being less reliable than the determination of IGF-I and somatotropin in serum.

Acromegaly↗
PubMed1993

[Acute pyelonephritis in diabetic patients].

Urinary tract infections rank first among the infections of patients with diabetes mellitus. They are encouraged by chronic hyperglycaemia and occur more frequently in diabetic women aged over 50 who suffer from disorders of the autonomic nervous system responsible for disturbances of bladder voiding. Another facilitating factor in younger women is pregnancy. Acute pyelonephritis is more dangerous than in non-diabetic populations, being often painless and therefore neglected. An unexplained blood glucose imbalance may be the only manifestation of acute pyelonephritis. In these patients, pyelonephritis is more frequently complicated by pyonephritis or papillary necrosis, both capable of threatening the patient's life or renal function. Moreover, since the diabetic kidney is exposed to a specific glomerulopathy with nephroangiosclerosis and interstitial lesions, all infections may aggravate these lesions, and they must be treated vigorously. Antibiotics may be less effective due to reduction of their tissue levels, and relapses, more frequent and resistant to treatment, may call for prophylactic treatment in certain patients. This is why urinary tract infections must be detected systematically and with a frequency which depends on the presence or absence of facilitating factors: female sex, age, neuropathy, mechanical causes and pregnancy. Using dipsticks that detect urinary leucocytes and nitrates makes detection easier and less costly.

Acute Disease↗
PubMed1993

Epidemiology, development and treatment of end-stage renal failure in type 2 (non-insulin-dependent) diabetes mellitus. The case of mainland France and of overseas French territories.

The prevalence of diabetes mellitus among patients treated for end-stage renal failure by dialysis in France was studied in two stages (UREMIDIAB Study). The first stage consisted of a questionnaire which was mailed to all dialysis centres in mainland France. The response rate was 80.8%, resulting in a study population of 12,903 patients. Of these patients 884 were declared diabetic (6.9%). Later 295 of them were interviewed by seven specially-trained physicians who checked the medical records together with the nephrologist in charge. Plasma C-peptide was measured in almost all of the patients. Effectively, 1.4% were found to have Type 1 diabetes and 5.5%, Type 2. Diabetic nephropathy was found to be the only primary renal diagnosis among 93.9% of Type 1 diabetic patients and 36.8% of Type 2. Of the latter 51.6% had a non-diabetic cause of renal failure. In the second stage a survey was later conducted in 13 of 14 dialysis centres located in the remote overseas French territories. Among 934 patients 1.04% were Type 1 diabetic and 19.67% Type 2 (22.9% altogether). Type 2 diabetic patients treated overseas were essentially non-Caucasians (92.6%). The sex ratio was 0.54 in the overseas territories vs 1.4 in the mainland. We conclude that the prevalence of diabetes among people on dialysis is low in mainland France. But there are striking differences in the prevalence of Type 2 diabetes among dialysis patients in mainland France and its overseas territories. These differences are not related to access to dialysis facilities.

Adult↗
PubMed1993

[Segmental arterial compliance of the radial artery: physiological role of age, hypertension and type I insulin-dependent-diabetes].

OBJECTIVE: To study the structural modifications of a muscular and medium-size radial artery as regards age, in normal subjects (NT) and HT and DTI. MATERIAL AND METHODS: Transverse study with 39 NT aged 48 +/- 16 years, were compared to 22 HT, aged 50 +/- 11 years, and to 22 DT aged 37 +/- 12 years. An echo-tracking system (NIUS 01, Asulabs, Neuchatel, Switzerland) were used to measure the systolic (Ds) and diastolic diameter (Dd) and derive three indices of compliance and storage capacity: systolo-diastolic variation of cross sectional area VSCA = tau [(Ds2/4)-(Dd2/4)] mm2, operative arterial compliance CA = tau Dd (Ds-Dd)/2 (PAS-PAD) in mm2/mmHg. RESULTS: 1. In NT, Ds and Dd increased significantly with age (p < 0.01), likewise the VSCA, and CA (p < 0.002). 2. In HT and DTI, when age was taken into account, the Ds and Dd were significantly greater than in control but VCSA and CA were higher in HT and lower in DT. CONCLUSION: Similar to ageing changes in NT, HT lead to increase in medium-size radial artery the diameter and storage capacity, while to decrease in DT. This suggests that opposite cardiovascular load induce opposite modifications in arterial wall structure leading to reduce the wall stress.

Adult↗
PubMed1993

[Cost of the diabetic foot].

Among the long term complications of diabetes, leg and foot problems frequently associated with chronic nonhealing wounds constitute a heavy economic cost previously evaluated in some countries. This specific cost has not yet been calculated in France. This study represents the first "estimation" of the frequency and cost of these complications in our country. Methodological obstacles must be considered related to a large variety of clinical situations all covered by the word "diabetic foot", neurotrophic or ischemic origin, and the heterogeneity of the therapeutical approach more or less expensive. We have estimated the incidence of leg and foot problems about 50,000 to 60,000 per years, 20,000 to 25,000 requiring an inpatient treatment for a neurotrophic complication and 10,000 to 15,000 for an ischemic problem (frequently followed by a limited or a large amputation). The annual total cost, direct plus indirect, calculated on this basis should be: 3,750 millions of francs/year (about 700 millions of US $). This value must be compared to the total cost of diabetes in France 12,000 to 18,000 millions of francs/year when considering 1 to 1.5 million diabetic patients. Thus leg and foot problems appear to constitute a prominent part of the economical cost of diabetes in our country as in others developed countries. Multidisciplinary and specialized structures for the care and prevention of such complications of diabetes must be developed as new therapeutical approaches to reduce this incidence, the duration of healing and the risk of relapse.

Amputation, Surgical↗