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Type 2 diabetes mellitus is a major metabolic disease in developed countries, and preferentially affects low-income groups and/or people from Southern extraction. Migrants are especially at risk. In Belgium, a large population of workers emigrated in the 50s and 60s, especially from rural areas of Southern Italy and Sicily. We tested the hypothesis that type 2 diabetes mellitus' phenotype in these Italian migrants could differ from that observed in autochthonous Belgian subjects. We retrospectively compared the clinical files of 485 patients with type 2 diabetes either of Belgian (n=445) or Italian origin (n=40). Italians were younger at diagnosis (46 +/- 14 vs. 52 +/- 13 years, P0.01), shorter, had a lower education and a stronger family record of diabetes (89 vs. 47%, P0.01). They had similar BMIs (31 +/- 6) and similar or slightly worse degree of sedentarity (75%). We further compared this Italian group to 115 Belgians subjects matched for age, sex, and education. Known duration of diabetes (16 years), smoking and drinking habits, use of oral hypoglycaemic, antihypertensive and hypolipaemic drugs, complications, CRP, estimated glomerular filtration rate, micro-albuminuria prevalence, blood pressure, insulin sensitivity/ beta-cell function estimated by HOMA modelling, as well as fat mass indirectly estimated by impedancemetry were not significantly different between the two populations. There was a non significant trend toward higher HbAlc (8.7 +/- 2 vs. 8.2 +/- 2%, NS) in Italian subjects whose LDL-cholesterol was however significantly lower (105 +/- 31 vs. 120 +/- 33 mg.dL-1, P0.01) as well as folic acid (5 + 1.7 vs. 6.7 +/- 4, P0.001). Insulin dose was higher (0.77 +/- 0.4 vs. 0.48 +/- 0.3 IU.day-1, P0.001) and abdominal obesity less prevalent in males (33 vs. 58%, P0.01) of this group. Thus, Italian diabetic subjects in Belgium exhibit higher insulin requirements despite similar/better BMI, known duration of diabetes, HOMA indices, use of oral antidiabetic drugs, abdominal obesity and slightly higher HbA1c. This points towards different dietary habits, as do the differences in folic acid and LDL-cholesterol; different patterns of exercise may also play a role. Higher family record of diabetes may be genetic, but may also be biased by tighter family structure in subjects of Italian extraction.

BACKGROUND: Plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), of their N-terminal pro-peptides, of endothelin-1 (ET-1), and big endothelin-1 (big ET-1) have diagnostic and prognostic significance in congestive heart failure (CHF). However, their respective values as a predictor of survival remain controversial and have never been directly compared in severe CHF. METHODS AND RESULTS: We analyzed, in 47 patients with severe CHF (New York Heart Association [NYHA] class III to IV; age 66 +/- 8 years, ejection fraction 20 +/- 6%), the prognostic performance of a panel of neurohormones and assays (N-terminal pro-ANP 1-25, 68-98 by radioimmunoassay [RIA], and 1-98 by enzyme-linked immunosorbent assay [ELISA], BNP by RIA and immunoradiometric assay [IRMA], N-terminal pro-BNP by Elisa, ET-1 by RIA, and big ET-1 by RIA and Elisa. Data were compared with 40 patients with mild to moderate CHF [NYHA I-II] and 30 healthy subjects. After a follow-up of 81 +/- 15 months, there were 34 deaths and 1 heart transplant. All neurohormones were significantly higher at baseline in patients with severe than in mild to moderate CHF or healthy subjects (all P < .001). Although all neurohormones but BNP IRMA were significant predictors of survival in univariate analysis, only big ET-1 RIA and ET-1 were independent predictors of survival (improvement chi(2): 7.5 and 4.6, P < .01 and P < .05). Using medians as cutpoints of big ET-1 RIA and ET-1, 2 severe CHF populations were defined with a different outcome (5-year survival: 55 versus 18%, P < .01). CONCLUSIONS: Big ET-1 and ET-1 are strong independent predictors of survival in patients with severe CHF and better for this purpose than natriuretic peptides or their pro-peptides. These markers allow easily to identify a population with a very high risk mortality eligible for more aggressive therapies.

BACKGROUND: Cardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice. METHODS: We studied the diagnostic and prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2-year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40). RESULTS: Plasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF displayed a significant and continuous increase from CTR to CAD, CHF I-II and III-IV. Receiver-operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2-year prognosis revealed that N-proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high-mortality group. CONCLUSION: Plasma N-proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N-proANF levels in this setting suggest an early humoral activation.

Dietary zinc-deficiency induces a striking reduction and a cyclic pattern of food intake in rodents. To elucidate the mechanisms for these effects, we studied the hypothalamic content, synthesis, and distribution of galanin (GAL) and neuropeptide Y (NPY) during zinc deficiency and refeeding in the rat. In Wistar rats, three weeks of zinc-deprivation consistently induced a reduction and a cyclic pattern of night- and day-time food intake, as well as of water intake. This was accompanied in zinc-deficient (ZD) rats, and to a lesser extent in pair-fed (PF) rats, by a decrease of hypothalamic GAL mRNA concentration (CTR: 100 +/- 8, ZD: 61 +/- 4, PF: 78 +/- 2 arbitrary densitometric units, ADU, P < 0.01) and an increase of hypothalamic NPY (CTR: 100 +/- 11, ZD: 154 +/- 10, PF: 126 +/- 4 ADU, P < 0.05), without peptide modification. The two neuropeptidergic systems were not affected by the cycles of feeding, with the exception of the NPY-immunoreactivity in the suprachiasmatic nuclei (geniculo-hypothalamic tract), that was inversely correlated to the food intake in both ZD and PF animals. In a second experiment, we showed that zinc-repletion for 4 days suppressed the behaviour induced by a two-week zinc-deprivation, and reversed the increase of NPY mRNA in ZD animals. We finally demonstrated that zinc-deficiency induced a similar behaviour in Zucker rats. However, in these rats whose synthesis of NPY is constitutively up-regulated, no change of NPY synthesis was observed in ZD rats, suggesting that the increase observed in Wistar is adaptative rather than instrumental to the abnormal food intake. In conclusion, we have further characterized the cyclic feeding behaviour of the zinc-deficient Wistar rats, and shown in these animals a decreased activity of the GAL system and an increased activity of the NPY system, likely corresponding to a compensatory response of the two neuropeptidergic systems, as observed in food-deprived animals. As spontaneous food intake of ZD rats does not increase, a resistance to NPY could also be present. These behavioural and neuropeptidergic changes were partially reversed by reintroduction of zinc in the diet. In Zucker rats, the same behaviour occurred despite an insensitivity of the NPY system to the zinc-deficiency. In addition, we describe a nutritional regulation of the NPY-immunoreactivity in the geniculo-hypothalamic tract, that could constitute the substrate of circadian rhythm modulation by timed feeding.

Transcription of the human growth hormone gene can start in vitro and in vivo 197 base pairs upstream from the cap site of growth hormone mRNA (Courtois, S. J., Lafontaine, D., and Rousseau, G. G. (1992) J. Biol. Chem. 267, 19736-19743). We have now characterized the mRNA that originates from this optional promoter and have found that it occurs in human hypophysis and placenta but not in 10 other tissues. This mRNA contains an open reading frame for a protein of 107 residues that shares sequence similarity with three domains of hepatic nuclear factor-1alpha. With antibodies directed against a peptide corresponding to the C terminus of this protein, immunoreactive material was detected in a subset of cells of the adenohypophysis. When fused to the DNA-binding domain of the yeast transcription factor GAL4, the protein stimulated transcription from a GAL4-sensitive reporter gene in transiently transfected pituitary and placental cells.

Background Endothelin-1, a vasoconstrictive peptide released by endothelium, may be involved in the pathophysiology of hypertension. The goal of the present study was to evaluate the role of endogenous endothelin-1 in renal hypertension in dogs. The model of hypertension consisted of silk tissue wrapping of the left kidney, which produced hypertension associated with perinephritis after 6 to 8 weeks. Methods and Results Thirty-two anesthetized open chest dogs were studied randomly: 8 dogs with perinephritic hypertension received the nonpeptidic ET A -ET B receptor antagonist bosentan (group 1); 8 other hypertensive dogs received the vehicle solution (group 2); 8 healthy dogs received bosentan (group 3); and 8 healthy dogs received the vehicle solution (group 4). Bosentan was injected as an intravenous bolus (3 mg/kg) followed by a 1-hour infusion at a rate of 7 mg · kg −1 · h −1 . In hypertensive dogs, bosentan produced a similar decrease ( P =.0001) of both left ventricular systolic and mean aortic pressures, which averaged 38 mm Hg (−22% and −24%, respectively). These parameters remained unchanged with the vehicle solution. Left ventricular end-diastolic and left atrial pressures also declined significantly with bosentan ( P =.0005 and P P =.004). Vehicle solution had no effect. Plasma endothelin-1 levels, similar under basal conditions in healthy and hypertensive dogs, increased 30-fold with bosentan ( P =.0001). Conclusions Specific endothelin-1 receptor antagonism markedly lowers blood pressure in experimental hypertension but is less effective on blood pressure of healthy animals. This suggests that endothelin-1 plays a role in the pathophysiology of hypertension but contributes to a lesser extent to the maintenance of normal blood pressure. This role of endothelin-1 is unrelated to its plasma levels. The increase of plasma endothelin-1 with bosentan, due either to a displacement of endothelin-1 from its receptor or to a feedback mechanism, does not prevent this blood pressure reduction.

To further investigate how sex steroids regulate galanin (GAL) in the rat pituitary and hypothalamus, we examined the effects of prepubertal gonadectomy (Gx) and long-term (9 weeks) replacement with estradiol (E2) or testosterone (T) on pituitary and hypothalamic GAL concentrations in Wistar rats (5-6/group). Sham-operated animals served as controls (CTR). Pituitary GAL concentration was markedly higher in random-cycling CTR-females than in CTR-males (1391 +/- 247 vs 39 +/- 5 pg/mg protein, P < 0.01) and decreased after Gx only in females (20 +/- 3 pg/mg protein, P < 0.01). E2 strongly increased pituitary GAL in Gx-females and Gx-males (4470 +/- 365 and 3853 +/- 347 pg/mg protein, P < 0.01), whereas T had no effect. Inversely, hypothalamic GAL was higher in CTR males than in CTR females (5.4 +/- 0.3 vs 4.0 +/- 0.5 ng/mg protein, P < 0.05), and decreased significantly after gonadectomy in males (3.7 +/- 0.2 ng/mg protein, P < 0.01). The only steroid treatment that significantly modified hypothalamic GAL in Gx animals was administration of E2 to females (5.7 +/- 0.4 ng/mg protein, P < 0.01 vs non-treated Gx). We also studied in hypophysectomized (Hx) rats (8/group) the effects of sex steroids on hypothalamic GAL concentration and distribution. The low hypothalamic GAL concentration observed in male and female Hx rats (1.0 +/- 0.1 ng/mg protein) was significantly increased by T in males and in females (respectively, by 40% and by 50%, P < 0.02) and by E2 in males (by 60%, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

We report a case of association between genetic haemochromatosis and mixed gonadal dysgenesis. To our knowledge, this case is the first reported in the literature. We discuss the mechanisms of hypogonadism observed in this patient.

The use of retroviral drugs in the treatment of infection by human immunodeficiency virus (HIV) is associated, especially for first generations, with side effects such as lipodystrophy, fatty liver and insulin resistance, which may trigger secondary diabetes or worsen existing diabetes. The use of Glucagon-Like Peptide-1 in obese patients with type 2 diabetes on HIV retroviral as an alternative to insulin therapy is not documented; we report the case of a 47-year-old treated with exenatide when insulin was discontinued. During the first year of treatment, exenatide, in combination with metformin and repaglinide, led to a weight loss of 14 kg and fat mass and waist circumference were respectively reduced from 31 to 25.5% and from 114 to 103 cm. Homeostatic model assessment (HOMA) was used to calculate β-cell secretion which increased from 50 to 78% and insulin sensitivity which increased from 28 to 51%, reflecting a decrease in HbA(1c) by 1.9%. Exenatide may be a new therapeutic option for HIV-infected type 2 diabetes patients undergoing retroviral therapy.

We performed a systematic survey of original papers published in The Lancet throughout the years 1945, 1946, 1970 and 1995. The Lancet was chosen due to a conservative layout through these years, and the year 1946 added to the analysis to ponder for any war-induced bias. The general layout and structure of the journal were indeed maintained throughout these years. The number of authors per paper increased steadily (from 1.7±1.3 in 1945 to 6.4±3.4 in 1995), as well as the number of papers written on behalf of investigation groups (from 1 in 1945 to 37 in 1995). Major changes were observed in the area of origin of the papers, from an overwhelming British Isles' preponderance (87% of papers published in 1945) to a partake with Continental Europe, America and international groups (27, 33, 15 and 12%, respectively of the 1995 papers). The most often addressed fields of medicine shifted from war-, surgery- and microbiology-related subjects in 1945 towards cardiology-, oncology-, and virus-related works in 1995. The most impressive and enduring change was the increase in the use of statistical tools for data analysis and presentation (0.3% of papers in 1945 vs. 60% in 1995). As one of the leading medical journals with a maintained layout over the last decades, The Lancet reflects changes in medical thinking and publishing. Multiauthorship, internationalisation of research, and (over) confidence into statistical analysis are becoming leading characteristics, some rather positive others not, of the corporate feeling within medical edition.

Both endogenous and exogenous hypercorticisms are associated with a modest increase of the activity of serum lactate dehydrogenase. Considering both the wide use of this parameter and the frequent prescription of corticosteroids in clinical practice, awareness of this phenomenon is useful to avoid unnecessary investigations.

BACKGROUND: Endothelin-1 (ET-1) and cardiac natriuretic peptide plasma concentrations have prognostic significance in congestive heart failure (CHF). However, their respective prognostic values in this setting have never been directly compared. METHODS AND RESULTS: We studied the prognostic performances of ET-1, N-terminal proatrial natriuretic factor (N-proANF), and brain natriuretic peptide (BNP) to predict the long-term cardiac mortality in fully treated patients with CHF. Peripheral plasma concentrations of the 3 peptides were measured in 109 patients (left ventricular ejection fraction [LVEF] < 35%) in New York Heart Association (NYHA) functional classes II (n = 65) or III to IV (n = 44). The outcome of the patients was evaluated 3 years after the beginning of the study, and a Cox regression model was used to identify predictors of death. Plasma concentrations of the 3 peptides increased with the severity of heart failure. By univariate analysis, 6 parameters were significantly associated with death during follow-up: ET-1 level, NYHA classes III to IV, N-proANF level, BNP level, LVEF, and age (all P < .01). By multivariate analysis, only ET-1 level and, to a lesser extent, N-proANF level contributed significantly and independently to risk stratification (chi2 = 53.4 and 12.8; P < .0001 and P < .001, respectively). CONCLUSION: In a group of patients in whom the vast majority were administered angiotensin-converting enzyme inhibitor therapy, plasma ET-1 and N-proANF concentrations identify better than several clinical markers a very high-risk group, fairly amenable to heart transplantation or new therapies.

Lefebvre S, De Paepe L, Abs R, Rahier J, Selvais P, Maiter D. Subcutaneous octreotide treatment of a growth hormone-releasing hormone-secreting bronchial carcinoid: superiority of continuous versus intermittent administration to control hormonal secretion. Eur J Endocrinol 1995;133:320–4. ISSN 0804–4643 Diagnosis of ectopic acromegaly was made in a 21-year-old female patient who 3 years before had undergone a right pneumectomy for a disseminated bronchial carcinoid. Plasma growth hormonereleasing hormone (GHRH) concentrations were markedly elevated (6440 ng/l; normal value S Lefebvre, Division of Rheumatology, Clinique du Refuge, Rue du Couvent 39, B-7700 Mouscron, Belgium

Endothelin-1 (ET-1) is a major vasoconstrictor peptide, first found in endothelial cells, and later in many other tissues, including the thyroid gland. We analysed the expression of the ET-1 gene in the rat thyroid gland and changes in ET-1 mRNA and peptide levels in goiter development and involution, two circumstances characterised by vascular changes. Thyroid hyperplasia was induced in adult Wistar rats by feeding a low iodine diet (LID) supplemented with 0·25% thiouracil for 10 days, and LID alone for 2 further days (H.12 group). Involution was induced by injecting 100 μg iodide and refeeding a normal diet during 6 h, 12 h, and 24 h (I.6h, I.12h, 1.24 h groups). Rats fed a normal iodine diet were used as controls. A specific 488 bp cDNA corresponding to the known sequence of pre-pro ET-1 was found by RT-PCR from RNA extracts in all thyroid experimental groups, as well as in lung and kidney which were used as positive controls. RP-HPLC analysis showed that ET-1 immunoreactivity eluted similarly as mature ET-1 During hyperplasia, ET-1 mRNA and peptide levels were increased 3·5- and 5-fold respectively. The relative volume of the vascular bed was more than doubled. During iodide-induced involution, the glandular ET-1 mRNA level remained elevated. The concentration of ET-1 peptide increased and was significantly greater at 12 h involution than in the H.12 group. At this time, the capillary reticulum reverted to individual capillaries and the vascular bed was significantly reduced. These data demonstrate that the ET-1 gene is expressed in the rat thyroid gland and that the ET-1 mRNA and peptide levels are increased during thyroid hyperplasia and remain elevated during a phase of rapid iodide-induced involution. These data suggest that changes in ET-1 production may play a role in control of thyroid gland trophic regulation and vascularity. Journal of Endocrinology (1994) 143, 65–74

To investigate whether pituitary-dependent hormones may regulate galanin (GAL) content, synthesis and distribution in the hypothalamus, female hypophysectomized Wistar rats were treated for 2 weeks with subcutaneous injections of thyroxine (T4, 2 x 1 microgram), bovine growth hormone (GH, 2 x 125 micrograms), cortisol (C, 50 micrograms), subcutaneous implants of beta-estradiol (E2, 5-mm implant, dilution 1:1), or with the combinations [T4+GH], [T4+GH+C+E2] or [T4+GH+C+E2 + rat PRL, 2 x 125 micrograms] (doses/100 g BW/day). Concentrations of GAL in the hypothalamus were measured by radioimmunoassay (RIA) and GAL mRNA abundance was quantified by Northern blot (6 rats/group); 2 rats/group were used for immunohistochemistry. Hypophysectomy caused decreases of hypothalamic GAL peptide and mRNA concentrations (by 70 and 50%, respectively; p < 0.05 vs. intact rats). GAL immunoreactivity disappeared in the median eminence (ME), but increased in the neurohypophyseal magnocellular neurons of hypophysectomized rats. Substitution with T4, GH, [T4+GH], C or E2 had no significant effect on total hypothalamic GAL peptide and GAL mRNA concentrations. A treatment combining [T4+GH+C+E2] increased hypothalamic GAL (1.9 +/- 0.1 vs. 1.2 +/- 0.1 ng/mg protein in untreated hypophysectomized rats; p < 0.01) and GAL mRNA concentrations (127 +/- 19 vs. 59 +/- 2 densitometric units in untreated rats, p < 0.001). Addition of PRL to this combined treatment had no further effect. Treatment with T4, GH, [T4+GH] or E2 enhanced GAL labeling in the ME of hypophysectomized rats. The effect of estrogens was restricted to the GnRH-rich lateral regions of the ME. The combined treatment with [T4+GH+C+E2] restored the ME GAL immunoreactivity to levels observed in intact rats. In contrast, the increased GAL labeling observed in magnocellular neurons after hypophysectomy was not influenced by any hormonal treatment. In conclusion, hypophysectomy leads to marked reductions of hypothalamic GAL and GAL mRNA concentrations, and of GAL immunoreactivity in the ME. These reductions are prevented in part by a combined hormonal treatment associating T4, GH, C and E2, but not by any hormone given alone. This suggests specific pituitary hormone-dependent regulation of the hypophysiotropic GAL neurons. In contrast, the increased GAL labeling in magnocellular neurons of hypophysectomized rats persists despite hormonal treatment and likely represents a lesional effect on the neurohypophyseal GAL system.

To understand better the relationship between hypothalamic galaninergic neurons and the pituitary gland, we studied the effects of hypophysectomy on hypothalamic galanin (GAL) content and distribution by radioimmunoassay and immunohistochemistry, and on GAL mRNA by Northern blot analysis. Three weeks after hypophysectomy, performed at 5 or 8 weeks of age, the hypothalamic concentrations of GAL and GAL mRNA were reduced by 30-50% in both male and female rats, compared to age- and sex-matched controls. Similar reverse-phase HPLC retention times of hypothalamic GAL were observed in intact and hypophysectomized rats. The reduction of hypothalamic GAL concentration following hypophysectomy was time-dependent, as peptide levels were unaffected one week after surgery. Immunohistochemistry showed regional differences in the effect of hypophysectomy on galaninergic neurons. In the hypophysiotropic hypothalamus, the scarce GAL immunoreactivity normally observed in the arcuate nuclei was no longer detectable in hypophysectomized rats, and the intense GAL immunoreactivity of the external zone of the median eminence progressively decreased and completely disappeared 3 and 6 weeks after hypophysectomy. In contrast, in the neurohypophyseal system, there was an increase of GAL labelling of the perikarya and emerging axons in the supraoptic and lateral-paraventricular nuclei, 1 and 3 weeks after hypophysectomy, that disappeared 6 weeks after hypophysectomy. An increase of GAL immunoreactivity was also observed in the internal zone of the median eminence 1 week but not 3 weeks after hypophysectomy. We conclude that hypophysectomy reduces the content of GAL and GAL mRNA in the rat hypothalamus. These changes are time-dependent and clearly detected after 3 weeks. The neurohypophyseal and hypophysiotropic galaninergic systems respond differently to hypophysectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

But Un traitement par exenatide chez des patients diabetiques de type 2 est habituellement associe a une reduction de poids et a une amelioration de l’equilibre glycemique. L’objet de notre etude est d’analyser la relation entre cette perte ponderale et la diminution des taux d’HbA 1c chez des sujets diabetiques de type 2 obeses traites par exenatide pendant 3, 6 et 12 mois. Patients et Methodes 299 patients diabetiques de type 2 obeses (55 % sujets masculins) ont ete recrutes dans 14 hopitaux du Reseau hospitalier. L’exenatide (Byetta) a ete prescrit a la dose de 5 μg deux fois par jour puis, en cas de bonne tolerance, de 10 μg deux fois par jour en association avec une bitherapie par sulfamide et metformine a dose maximale. Nous disposons d’un suivi en terme de poids et d’HbA 1c a 3, 6 et 12 mois apres l’instauration du traitement chez respectivement 230 (âge : 58 ± 11 ans [moyenne ± 1DS], duree du diabete [DD] 10 ± 7 ans) [groupe 1], 160 (âge 59 ± 10; DD : 10 ± 6) [groupe 2] et 94 sujets (âge 59 ± 11 ; DD : 10 ± 6) [groupe 3]. Les correlations entre perte de poids et delta du taux d’HbA 1c ont ete analysees par le coefficient de correlation (r) de Pearson. Resultats Dans les groupes 1, 2 et 3, les poids ont baisse de 97 ± 20 a 94 ± 20 kg (3 mois), 97 ± 21 a 93 ± 21 kg (6 mois) et 98 ± 20 a 94 ± 22 kg (12 mois). Les taux d’HbA 1c dans les trois groupes ont diminue de 9,0 ± 1,3 a 7,8 ± 1,1 % (groupe 1), 9,1 ± 1,5 a 7,7 ± 1,4 % (groupe 2) et de 9,1 ± 1,4 a 7,5 ± 1,2 % (groupe 3). Il existait une correlation significative entre perte de poids et abaissement de l’HbA 1c a 3 mois (r = 0,213 ; p = 0,001), 6 mois (r = 0,213 ; p = 0,001) et 12 mois (r = 0,241 ; p = 0,019). Conclusion L’administration d’exenatide a des patients diabetiques de type 2 obeses est efficace en terme de perte ponderale et de controle glycemique des le 3 e mois de suivi. Cette amelioration est maintenue apres 12 mois. Il existe a tous les temps une relation significative entre la perte de poids et la diminution du taux de l’HbA 1c

Superiority of Big Endothelin-1 and Endothelin-1 over Natriuretic Peptides To Predict Survival in Severe Congestive Heart Failure Michel F. Rousseau,RonaldVanBeneden,OlivierGurne, PhilippeL. Selvais, Annie R. Robert, Sylvie A. Ahn, Hubert G. Pouleur, Jean Marie Ketelslegers2—Division of Cardiology, University of Louvain, Brussels, Belgium; Diabetes and Nutrition Unit, University of Louvain, Brussels, Belgium; School of Public Health, University of Louvain, Brussels, Belgium

A case of bilateral breast infiltration as the initial manifestation of FAB-L3 leukemia during pregnancy is reported. This rare presentation is usually associated with Burkitt's lymphoma or FAB-L3 leukemia. A high suspicion of the presence of hematologic malignancy and appropriate evaluation are indicated in the presence of this clinical manifestation.