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Background: The genetic characterization of obese individuals could clarify the molecular mechanisms underlying body weight regulation and lead to targeted therapy. Here we report variants of the proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) genes detected in severely obese adults living in southern Italy. Methods: A total of 196 unrelated nondiabetic severely obese individuals [111 females and 85 males; mean (SD) age, 32.2 (11.5) years; mean body mass index, 48.8 (8.1) kg/m2] and 100 normal-weight healthy volunteers (34 males and 66 females) entered the study. POMC and MC4R were genotyped by sequencing analysis. Leptin, insulin, glucose, and the lipid profile were measured in fasting serum samples. We used the protein truncation test to verify the stop-codon mutation. Anthropometric measurements, sitting blood pressure, and heart rate were also recorded. Results: Of the obese participants, 1.5% had mutations in POMC exon 3 (new mutations, P231L and E244X; known, R236G) and 2.5% had MC4R mutations (new mutations, W174C, Q43X, S19fsX51, and I317V; known, A175T). These mutations were not present in the controls. Gene polymorphisms were identified in similar percentages of severely obese and nonobese individuals, i.e., respectively, 52.5% and 51% (POMC) and 1% and 2% (MC4R). Conclusions: We detected 2 new POMC mutations and 4 new MC4R mutations in a large number of severely obese adults living in southern Italy. These mutations, not present in normal-weight individuals, are further evidence that defects in the melanocortin pathway are related to severe obesity.

The aim of the study was to evaluate the relationship between basal metabolic rate (BMR) and bioelectrical impedance analysis (BIA) in undernourished female patients with anorexia nervosa. Participants were 86 female patients with anorexia nervosa (age 20.8+/-4.7 years; weight 39.3+/-5.2 kg; body mass index 15.4+/-1.6 kg m-2). BMR was measured by indirect calorimetry and single-frequency BIA was determined at 50 kHz on the whole body. The BIA variables considered were resistance, reactance, phase angle and the bioimpedance index (height2/resistance). Fat-free mass was calculated from subcutaneous skin fold thickness. In the study group BMR was 3782+/-661 kJ d-1 while bioimpedance index varied between 27.6 and 49.9 cm2 Omega-1 and phase angle between 2.54 degrees and 6.49 degrees. BMR was significantly correlated with weight, height, body mass index and fat-free mass, and, among BIA variables, with reactance and phase angle. Multiple regression analysis indicated that phase angle was a predictor of BMR not only when solely BIA variables were considered, but also in combination with either weight and age or fat-free mass. In conclusion, phase angle emerged as a strong predictor of BMR in female patients with anorexia nervosa. Nevertheless, further studies are necessary to confirm this finding in other forms of protein energy malnutrition and justify the inclusion of BIA variables in the equations used to predict BMR in the clinical setting.

Protein energy malnutrition due to anorexia nervosa, either restrictive or bulimic, requires an integrated medical psychiatric intervention to be treated. The aim of this study was to evaluate the effectiveness of this integrated treatment in severely malnourished anorectic patients requiring to be hospitalized in Psychiatry Unit. Fifteen patients (14 females, 1 male, mean age 19.6 +/- 4.7 years, body mass index 14.0 +/- 1.9 kg/m2) 13 of whom affected by restrictive anorexia nervosa and 2 by bulimic anorexia nervosa, have been hospitalized in the Psychiatry Unit of the Federico II University Hospital, Naples from September 2000 to July 2003, always without requiring compulsory sanitary treatment. Hospitalization was due to failure of the outpatient treatment in all of them, complicated by uncontrolled weight loss in 7, hydroelectrolytic unbalance in 2, edema in 1 patient. All were hypotensive and 4 had marked bradycardia. Forced nutrition was never necessary. Enteral nutrition by nasogastric tube was prescribed in 4 patients, oral nutrition supplements with diet in 4 and only diet in the remaining 7. All patients received vitamin and mineral supplements, if necessary parenterally. A mild body weight increase and satisfactory normalization of biochemical parameters was obtained in all patients during hospitalization. Thereafter they were enrolled in an outpatient integrated medical/psychiatric protocol, including group therapy. Only in 1 case, a few months later, a second hospitalization was necessary. In conclusion, integrated medical psychiatric treatment represents an effective intervention also in severely malnourished anorectic patient requiring hospitalization.

Background/Aims: In the absence of other causes, obesity increases the risk of liver disease. We evaluated the prevalence and degree of metabolic and hepatic abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type II–III obesity in a metropolitan area of South Italy. Methods: 187 (81 M, 106 F) young adult non-diabetic obese patients, age range 18–50 years (mean 31.9 ± 8.8), body mass index (BMI) ≧30 (mean 47.5 ± 9.6), consecutively admitted from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into the study. Patients were divided into two groups: (1) BMI 30.0–39.9, and (2) BMI≧40. Ultrasound detected liver steatosis was classified as: (I) mild; (II) moderate, and (III) severe. Results: All patients, except 4, showed a variable degree of steatosis: mild was more frequent among females, severe steatosis present only in grade III obesi ty, with higher prevalence in males than in females (p < 0.001). Mean serum transaminases, in particular alanine aminotrasferase (ALT), increased according to BMI and degree of steatosis. Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels increased with BMI, particularly in severe steatosis. In group 2, patients with BMI≧40 showed a positive correlation between ferritin, aspartate aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma-glutamyltransferase (γGT) (r = 0.51, p < 0.007), between serum triglycerides (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and ALT (r = 0.30, p < 0.03) and γGT (r = 0.35, p < 0.012). In group 2 patients with severe steatosis the prevalence of metabolic syndrome according to Adult Treatment Panel III (ATP III) was 40%. Conclusion: These data suggest that, in young adult non-diabetic grade III obese patients, fatty liver is always present and strictly related to insulin resistance which, in the presence of severe liver steatosis, is also related to serum ferritin.

PP181-SUN LOCK THERAPY WITH DAPTOMYCIN FOR THE TREATMENT OF METHICILLIN RESISTANT S. EPIDERMIDIS INFECTIONS IN PATIENTS ON LONG-TERM HOME PARENTERAL NUTRITION L. Santarpia1, M.C. Pagano1, A. Buonomo2, M. Foggia2, L. Alfonsi1, F. Contaldo1, F. Pasanisi1. 1Department of Clinical Medicine and Surgery, Internal Medicine and Clinical Nutrition, 2Department of Clinical Medicine and Surgery, Infectious Disease, Federico II University, Naples, Italy

Objective We worked to identify predictors of survival in patients with carcinomatosis on home parenteral nutrition (HPN). Methods Survival rate was evaluated in 152 terminal patients (45 men and 107 women) with peritoneal carcinosis on HPN. Selected anthropometric measurements (weight and body mass index), laboratory tests (serum albumin, cholesterol, cholinesterase [CHE], hemoglobin, and lymphocyte count) and clinical variables (ascites, pain, and vomiting) were recorded at baseline. A Karnofsky Performance Status (KPS) was also determined. Results Sites of primary cancer were the stomach in 31.6%, ovaries in 27.6%, colorectum in 19.7%, and other in 21.1%. At baseline patients had abnormally low values: 55.3% had a body mass index no greater than 20.0 kg/m 2 , 40.4% had a serum albumin level lower than 3.0 g/dL, 55.7% had a lymphocyte count no higher than 1200/mm 3 , 54.6% had a cholesterol level lower than 160 mg/dL, and 63.1% had a CHE level lower than 5400 U/L. Pain, ascites, vomiting, and a KPS score no higher than 40 were observed in 44.1%, 55.3%, 76.3%, and 51.3% of patients, respectively. Survival ranged from 6 to 1269 d (median 45 d). Patients with a KPS score no higher than 40 had shorter survival than did patients with a KPS score of at least 50 (median 28.5 versus 81, P = 0.0001). Multivariate analysis ( R 2 = 0.152 for the entire model) indicated that KPS ( P = 0.01) and CHE ( P = 0.034) were significant predictors of survival. Moreover, three different combinations of selected clinical and laboratory variables identified patients who survived fewer than 60 d (high specificity). Conclusions Time of survival widely varied among terminal cancer patients; identification of predictive factors could help to draw up guidelines to improve indications for HPN. In this study, traditional predictors (KPS, albumin, pain, and vomiting) and CHE level appeared to be a useful survival predictor index in incurable patients with peritoneal carcinosis on HPN.

Summary Among the strategies suggested to face obesity epidemics there is also a mere reduction of only 100–200 kcal day, i.e. less mouthfuls of food and a little more walking every day. Are these proposals “simple and feasible” or, vice versa, “simplicistic and unrealistic” solutions? A possible source of such confusion comes firstly from dietary guidelines: the “food pyramid” may easily lead to misinterpretation as low-fat foods enriched in simple sugars produce similar metabolic abnormalities as saturated fat rich foods. Replacement of fruit derived fructose with other fructose-enriched beverages is not adequately considered. In total, 45–60 min of moderately intense physical activity, instead of “few steps”, daily appears a more realistic evaluation of the role of physical activity in energy balance but is still an unrealistic intervention strategy in many obese individuals requiring a long preliminary rehabilitation period. Another complaint is the current poor distinction between “preventive, population oriented” and “therapeutic, clinical” intervention strategies possibly due to the long duration of the latent “preclinical” phase of the disease and the scarcity of safe and effective drugs. Obesity may be considered a “culture-bound” disease and as such it requires a proper cultural, political and educational strategies. The number of obesity clinics worldwide is too limited; educational interventions in the crucial period of the developmental age are lacky. The social science content of medical school curricula, and teaching healthy behaviours, needs to be improved. In conclusion, a deeper reflection from Medical Societies on the relationship between the negative aspects of the “transition diet” and “globalization process” may help to produce really “simple” and more successful strategies against obesity epidemics and its complications.

C.A., a 23-year old male was admitted in the clinical nutrition medical ward for severe, complicated protein-energy malnutrition (PEM) [body mass index (BMI) 11.08 kg/m2; body weight kg 35.81 due to major eating disorders. C.A.'s personality was narcissistic, with a rigid psychic structure. During hospitalitation (lasted 72 days) two acute episodes (a possibly self-inflicted damage and a persecution feeling) occurred that we consider as part of the "crisis phase", the period in which the patient's restrictive behaviour is no longer able to keep his personality equilibrium stable. The patient was treated by an integrated medical and psychiatric approach, including periods of never forced parenteral nutrition, nutritional and intensive psychoterapeutic interventions. For a short period the patient received also a pharmacological support (aloperidol orally). Treatment was successful and the patient was discharged completely autonomous and followed up on an outpatient basis. After about one year follow-up he is still in good clinical condition and in sufficient psychological equilibrium.

To analyse the association of the UCP2 gene, alone or in combination with the PPARgamma2 gene, with obesity.Cross-sectional, case-control study.From a working population of 4500 Italian Caucasian employees of the Italian telephone company participating in a firm-sponsored health screening programme, we selected all those with obesity [n = 122; body mass index (BMI)or = 30 kg/m2]. For each case, three nonobese age- and sex-matched individuals were selected as controls from the same population (n = 374). Included in the study were also 76 severely obese (BMIor = 40 kg/m2) patients consecutively admitted to the obesity clinic of the department. Diabetic individuals were excluded.The -866G/A UCP2 and the Pro12Ala PPARgamma2 polymorphisms were determined on genomic DNA of the studied individuals. Several metabolic and anthropometric measures were also obtained, like plasma glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol and BMI.BMI, plasma glucose, insulin, triglycerides, total and HDL cholesterol were not significantly different in carriers and noncarriers of the -866G/A variant. No significant association was observed between the -866G/A UCP2 gene polymorphism and moderate or severe obesity. This was also observed when the UCP2 polymorphism was analysed in combination with the PPARgamma2 polymorphisms.The -866G/A variants of the UCP2 gene are not associated with either obesity or other features of the metabolic syndrome in the studied groups of the Italian population. This negative finding is not modified after a combined analysis of the UCP2 polymorphism and the Pro12Ala polymorphism of PPARgamma2.

The WHO has declared overweight and obesity as one of the top 10 risk conditions in the world and one of the top 5 in industrialized countries. Studies on twins, adopted children, family aggregation and ethnic groups confirm the contribution of genes to the development of obesity. Obesity-predisposing genes encode the molecular components of the physiological systems regulating energy balance, i.e. energy intake and expenditure, and consequently body composition (including fat stores). Studies of ethnic groups and in developing countries support the thrifty genotype hypothesis whereby genes, selected through the million-yearlong era of hunter–gatherers to afford a specific environmental pattern (including several hours of physical activity per day, continuously alternating of periods of feast with famine, etc.), are nowadays believed to predispose to obesity and diabetes. Actually this purported predisposing genetic pattern, developed to save energy, has produced an increasing prevalence of Overweight and Obesity in the agricultural (last 8–10,000 years) or recent industrialized (last 200 years) societies. The obesity epidemics actually exploded, as clearly appears in the US society, particularly in developing ages and in non caucasian populations, from the ‘‘80s onward, in less than one generation and not during the whole last century!’’ This is clearly confirmed by the massive epidemics of obesity and diabetes in aboriginal societies, very recently faced with westernized life styles. New, aggressive environmental and cultural factors have certainly played a role. As a matter of fact, food industry is currently able to manipulate the so called ‘‘food pyramid’’ by encouraging the consumption of low fat foods however enriched in simple sugars able to produce insulin-resistance and elevated post-prandial metabolic efficiency just as the harshly ‘‘banned’’ saturated fats do. This has led a tremendous confusion among the ‘‘consumers’’ and unspecialized physicians who have become ‘‘attracted’’ by irrational alternatives. Extreme but unrecognized sedentarism, in everyday work and leisure activities, and in the time spent to reach the working place, as well as the increase in elderly population have also reached their historical peak and do not tend to plateau. The whole process appears to be irreversible and spread all over the world! Nevertheless, overweight and obesity epidemics seem concomitant with another aspect of the very recent globalization process, the worldwide homogenization of the genetic and environmental, as well as socio-economic and cultural determinants. In other words, can the irreversible loss of the ethnic (biological and cultural) variety ‘‘per se’’, mostly due to progressive and massive urbanization and humanization of the territory, negatively affect our health? We ARTICLE IN PRESS

The Mediterranean diet is the lucky definition given by Ancel Keys of the food habits of some populations in the Mediterranean area. Dietary styles of this region may widely vary between coasts and inland. The total fat content of diets may vary from less than 30% in the traditional diet of Southern Italy to about 40% in the island of Crete. Carbohydrate and fibre rich foods also vary in terms of energy content, type and amount of sugars. Also proteinrich foods have large variations being mostly of vegetable origin rather than animal. Finally the original description of this diet also brings to mind the extensive physical activity, mainly related to work and outdoor leisure activities that prevailed in these populations until the sixties. Changes toward transition diet, the meaning of functional food and life style changes in the area at present are also discussed.

Objectives: Factors predicting clinical outcome in the short-term treatment of anorexia nervosa. Design: Longitudinal follow-up study. Setting: Department of Clinical and Experimental Medicine, “Federico II” University of Naples. Participants: Fifty-eight young anorectic women consecutively attending the outpatient Unit between January 1997 and December 2000. Main outcome measures: Body weight changes over six months’ follow-up. Results: Body weight changes in the short term was exclusively predicted by the prevalent underlying psychiatric disorder, being increased in the patients with prevalently depressive traits, decreased in those with psychotic features and unchanged in those with a prevalently narcissistic personality. Conclusions: The prevalent psychiatric disorder seems to predict clinical outcome in the short term. Body weight gain per se cannot always be the main target of medical intervention, at least in the early phase of the treatment of malnutrition secondary to major eating disorders.

The aim of this study was to compare how different diagnostic criteria can influence the estimation of obesity in children. Five hundred and eighty-seven children from Southern Italy were evaluated for the presence of obesity according to six different methods: two using Ideal Body Weight, according to Tanner and the National Center for Health Statistics, and four using Body Mass Index, according to Rolland-Cachera, Must, Cole (International Obesity Task Force) and the Centers for Disease Control and Prevention. Large discrepancies were found between old and new methods in identifying childhood obesity with respect to absolute prevalence, differences between the sexes, and age-related trends. The use of different weight-height indices, the employment of different cut-off points, the large differences between the reference populations, and the different time periods of data collection explain differences between methods. This should be always taken into consideration when data from different epidemiological or clinical studies are compared.

Catheter-related sepsis is a serious and common complication in patients receiving home parenteral nutrition (HPN). Prevention measures, prevalence of infections, types of agents and implanted central venous catheters (CVC), effectiveness of antibiotic therapy have been evaluated in 221 patients consecutively followed in our unit from January 1995 to December 2000. The clinical diagnosis of catheter-related infection was made using well-defined criteria. Patients were divided into two groups: A and B, receiving instructions with different modalities: standard (A) and detailed (B), respectively. Sixty CVC-related sepsis occurred in 32 (14%) patients. A multivariate analysis showed that the duration of HPN (P

Objective: To evaluate serum leptin levels in anorectic women, menstruating women with low body mass indexes (BMI) and normally menstruating women with normal BMI. Design: Prospective study. Setting: University clinics. Patient(s): Fourteen amenorrheic patients with anorexia nervosa (group A), 11 menstruating women with a BMI 2 (group B), and 20 normal controls. Main Outcome Measure(s): Determination of BMI, caloric intake, total fat mass, ovarian volume, and serum leptin, insulin-like growth factor I, FSH, LH, E 2 , PRL, and TSH levels. Intervention(s): None. Result(s): Mean BMI and fat mass were similar in groups A and B and significantly higher in controls. Mean caloric intake was significantly lower in group A than in group B and controls. Median serum leptin levels were significantly lower in group A than in group B and controls, and significantly lower in group B than in controls. Median serum insulin-like growth factor I levels were significantly lower in group A than in group B and controls. Binary segmentation analysis of groups A and B showed that LH was the most relevant variable in differentiating the two groups, followed by leptin. Conclusion(s): A threshold of leptin levels exist above which, even in the presence of low body mass indexes, the menstrual function is preserved.

OBJECTIVE: To assess body composition changes occurring in female anorectic patients after complete weight recovery. DESIGN: Longitudinal study. SUBJECTS: : Ten female patients with anorexia nervosa (age at baseline: 19.7+/-5.8 y) were studied both when undernourished (body mass index, BMI 14.8+/-1.3 kg/ m(2)) and after the achievement of a BMI >18.5 kg/m(2). The control group comprised 18 well-nourished women (age 20.1+/-4.4 y; BMI 19.0-23.0 kg/ m(2)). INTERVENTIONS: Fat mass and fat-free mass were determined by dual-energy X-ray absorptiometry. Skinfold thicknesses and circumferences were also measured. Arm muscle area and arm fat area were calculated by standard formulas. RESULTS: The undernourished patients had lower fat-free mass, fat mass, skinfold thicknesses and circumferences. After refeeding, fat mass represented 25-71%(mean 56%) of the mass regained, this percentage being directly related to the extent of weight gain. The increases in skinfolds and circumferences depended upon the site considered and were correlated to a various extent with those in weight or BMI. Skinfolds at biceps and abdominal sites and the waist-to-hip ratio remained significantly higher, whereas arm muscle circumference was significantly lower, in the refed group than in the control one. CONCLUSION: The percentage of fat in the weight regained by refed female anorectic patients was directly related to the extent of body mass increase. Refed anorectic patients appear to preferentially regain fat in the abdominal and triceps regions. Abnormalities in skinfolds (at biceps and abdominal sites), arm muscle area and waist-to-hip ratio still persist in refed anorectic patients in comparison to control healthy controls.

Despite current evidence suggesting that hemodynamic load is the fundamental stimulus to begin the sequence of biological events leading to the development of left ventricular hypertrophy, genotype, gender, body size, and less easily recognizable environmental factors may contribute to generate the cascade of molecular changes that eventually yield the increase in protein synthesis needed to increase left ventricular mass. However, even nonhemodynamic factors such as gender and body size eventually regulate the growth of left ventricular mass by at least in part influencing loading conditions. Consideration of measurable factors, such as gender, body size, and hemodynamic load, allows evaluation of individual echocardiographic left ventricular mass as the deviation from the level that would be required to face a gender-specific hemodynamic load at a given body size. Values of left ventricular mass that are inappropriately high for individual gender, body size, and hemodynamic load are associated with a high cardiovascular risk phenotype, even independent of the presence of arterial hypertension. Thus, the condition of inappropriately high left ventricular mass may be recognized as a more advanced stage of pathological structural changes initially induced by overload, going beyond the compensatory needs. The biological process that yields inappropriate left ventricular mass is probably linked to the protracted activity over time of biological mediators of left ventricular hypertrophy, such as proto-oncogenes and other growth factors, neurohormones, and cytokines, inducing structural modifications that initially compensate imposed overload but eventually change the structure of myocardial tissue and the composition of motor units.

Clinical, anthropometric, hematologic, and biochemical variables, evaluated immediately before starting nutritional treatment, were related to survival in 76 terminal-cancer patients with irreversible bowel obstruction receiving home parenteral nutrition. At baseline, abnormally low values were observed in the following percentages of patients: 40.8% for body mass index, 59.2% for serum albumin, 84.2% for hemoglobin, 48.7% for lymphocyte count, and 60% for serum cholesterol. Survival on home parenteral nutrition ranged between 6 and 301 d, with a median of 74 d. Hemoglobin, serum albumin and serum cholesterol were lower in patients with a survival of less than 3 mo. With regard to Karnofsky performance status, median survival times were 63 d for a score below or equal to 50 and 128 d for a score between 60 and 70. Albumin and a Karnofsky score above 50 (but not age, weight, body mass index, lymphocyte count, or cholesterol) emerged (with a positive sign) as predictors of survival. In conclusion, terminal-cancer patients with irreversible bowel obstruction are often malnourished, showing a high prevalence of anemia and hypoalbuminemia. Survival differs widely and can be predicted only to a limited extent from initial values of serum albumin and Karnofsky performance status.

We report on a patient with protein-losing enteropathy due to primitive intestinal lymphangiectasia with an early reversal of clinical and biochemical signs and a stable late reversal of pathologic signs after treatment with a hypolipidic diet enriched with medium-chain triacylglycerols.

To analyze possible early abnormalities in bone resorption in type 1 diabetes mellitus the urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline was evaluated by immunoassay in 26 prepubertal diabetic patients (mean age 7.8 ± 1.6 years, mean duration 3.0 ± 1.1 years) and 46 healthy children (age 8.3 ± 1.3 years). Relationships with growth parameters (height-standard deviation score, body mass index and height velocity during the year preceding the study) and metabolic control were sought. Longitudinal and ponderal growth was normal in diabetic children. Urinary collagen crosslink excretion was 88.4 ± 25 nmol/mmol creatinine (median 86, range 44–146) in diabetic patients and 65.6 ± 19 nmol/mmol creatinine (median 61, range 32–108) in controls (p = 0.0002). It was positively influenced by diabetic status (beta = 20.5) and negatively by age (beta = –6.41), controlling by sex and BMI (p = 0.0001). A positive correlation was found between collagen crosslinks and blood glucose (r = 0.48, p = 0.01) or HbA1c levels (r = 0.44, p = 0.02) evaluated at the time of the study, while no significant correlation was found with the mean HbA1c values assessed in the last year or throughout the whole duration of diabetes. Collagen crosslink excretion was significantly increased in patients who presented worsening of their metabolic control in the last 3 months. No relationship was found with the duration of disease or growth parameters. In conclusion, the elevated urinary excretion of collagen crosslinks in diabetic children indicates that bone resorption may be disturbed. Poor metabolic control influences the increased rate of bone resorption and may expose growing diabetic patients to a risk of bone loss.

Obesity is a multifactorial disease due to the influence of both genetic and environmental factors. Parents of 886 obese patients (427 boys and 459 girls, aged 1-18 years) were investigated by means of a questionnaire in order to study the factors associated with the onset of obesity in children and the relationship to genetic background. At presentation obese patients had a very high mean ideal body weight percent (IBW%) (154 +/- 19%, median 152%, range 120-246). A significantly higher mean IBW% was found in children of obese parents (one obese parent: 158 +/- 21%, median 156%, range 120-246; two obese parents 160 +/- 18%, median 158%, range 123-226) in comparison to children of normal weight parents (150 +/- 18%; median 147%, range 120-235; p = 0.0001 for children of one or two obese parents versus children of normal weight parents). Parents of 414 subjects (46.7%) (Group A) answered that obesity had always been present. The remaining 472 parents (53.3%) (Group B) stated that obesity had had a beginning at a mean age of 5.3 +/- 2.6 years (median 5.0 years, range 1.0-17.0). No difference was found in age at presentation, sex distribution, birth weight and number of obese parents between the two groups. Parents in Group B recalled an event associated with obesity onset in 197 cases (health event: 119 answers, psycho-social event: 78 answers). Genetic background did not influence this pattern of feedback. In conclusion, parents of obese subjects seek medical advice when obesity is severe. Pediatricians should exert strict surveillance on weight from a very young age. The recall in 22% patients of health or psychosocial events at the onset of obesity emphasizes that medical counselling is important when the occurrence of particular events in life may cause erroneous eating habits.

To study the involvement of gonadotropin-releasing hormone (GnRH) in glycosylation of circulating gonadotropin isoforms in anorexia nervosa (AN), 14 amenorrhoic patients with AN, 14 age-matched volunteers in early follicular phase, and five normal-weight re-fed patients with AN were investigated under baseline conditions and after acute administration of GnRH. Plasma gonadotropins were assayed using IRMA before and after concanavalin A affinity chromatography. Baseline plasma gonadotropin levels were lower for both AN and re-fed AN patients than in controls (P

Sarcopenia is a progressive and generalized loss of skeletal muscle mass (SM) and function which can also be found in obese adults. The aim of the study was to evaluate the prevalence of sarcopenia in 1 245 obese women (18 – 67 years, weight 114.7±24.5 kg; BMI 44.1±9.2; fat mass 49.0±6.2%) from Southern Italy. Body composition was evaluated by bioimpedance analysis (BIA) and SM calculated by using Janssen's equation; therefore the sex-specific cut-off points of percentage skeletal muscle index were used. The whole population was divided in two age groups: A (18-40 years; n. 808; weight 115.4±23.5 kg; BMI 43.8±8.8 kg/m2) and B (41-67 years; n. 438; weight 113.4±26.3 kg; BMI 44.8±9.9 kg/m2). In all the sample there was 2.7% moderate and 0.6% severe sarcopenia; in group A, 1.9% moderate and 0.6% severe sarcopenia whilst in group B 4.3% moderate and 0.7% severe sarcopenia. The results of our study suggest that, based on a screening examination by BIA, moderate/severe sarcopenia can be detected in an unselected middle-aged obese population. Further studies are required to clarify the diagnosis with functional tests.

Tommaselli AP, Valentino R, Savastano S, Randazzo G, Scalfi L, Contaldo F, Dorato M, Lombardi G. Altered glycosylation of pituitary gonadotropins in anorexia nervosa: an alternative explanation for amenorrhea. Eur J Endocrinol 1995;132:450–5. ISSN 0804–4643 To investigate the relevance of glycoprotein polymorphism to gonadotropin bioactivity in vivo, plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH), 17β-estradiol (E2), testosterone and sex hormone binding globulin (SHBG) levels in 17 amenorrheic women affected with anorexia nervosa (14–29 years) and 10 age-matched normally cycling women were evaluated. Plasma FSH and LH levels were assayed using radioimmunoassay (RIA) and immunoradiometric assay (IRMA) methods, before and after concanavalin A–Sepharose (Con A) affinity chromatography. Significant RIA–IRMA differences in FSH and LH plasma values were present only in women with anorexia nervosa (p < 0.005). Moreover, in these patients both FSH and LH showed a reduced binding to the Con A, expressed as a percentage of unbound, suggesting altered glycosylation of these moieties. In conclusion, these findings hypothesize the involvement of glycosylation polymorphism in RIA-IRMA differences; support the usefulness of both RIA and IRMA methods in FSH and LH evaluation, before and after Con A chromatography; and suggest a new pathogenetic pathway to explain amenorrhea in anorexia nervosa. Antonio P Tommaselli, Chair of Endocrinology, University Federico II, via Pansini, 5, 80131-Naples, Italy

For quantitative assessment of cardiac autonomic control, time and frequency domain measures of heart period variability were calculated by 24 h Holter recording in 10 young obese women with early-onset familial obesity and in 10 control subjects. Ultra low frequency and very low frequency power were lower in obese subjects than in controls (P < 0.05). High frequency power, a pure measure of vagal tone, was comparable between the two groups. However, low frequency power, which analysed over a 24 h Holter recording reflects parasympathetic more than sympathetic activity, was slightly lower in obese subjects than in controls (P = 0.06). Body mass index showed an inverse correlation with total power (r =-0.62; P < 0.05) and separately with ultra low (r = -0.59; P < 0.01), very low (r= -0.64; P < 0.005), low (r = -0.61; P < 0.005) and high frequency power (r =-0.53; P < 0.05). These results demonstrate a parasympathetic withdrawal increasing body weight. The reduction of ultra low frequency and very low frequency power, which are associated with sudden death, may help to explain the higher cardiovascular risk in obesity.

The effects of dexfenfluramine (dFE: 30 mg per os) on energy expenditure were evaluated in seven young obese male subjects (mean +/- s.d.: age 30.9 +/- 6.1 years; BMI 39.8 +/- 4.4 kg/m2). Each subject was submitted, on a double-blind protocol and by random order, to four tests in which dFE or placebo (Pla) were administered either in the fasting state or in combination with a mixed test meal. Energy expenditure was measured by indirect calorimetry for 60 min before (BMR) and from 90 to 330 min after dFE or Pla. In those cases where the protocol required it, a mixed test meal (5 MJ, 1200 kcal; percentage of protein, carbohydrate and fat: 15, 55, and 30 respectively) was eaten 120 min after dFE or Pla. In the fasting state resting metabolic rate increased after dFE (mean +/-s.d.: 0.49 +/- 0.20 kJ/min) but not after Pla (-0.04 +/- 0.16 kJ/min) in comparison to BMR, the difference between the two tests being highly significant (P < 0.01). Post-prandial thermogenesis (over 3h) was also significantly higher after dFE than after Pla (232 +/- 85 kJ vs. 181 +/- 73 kJ; P < 0.025). On the other hand, dFE did not affect respiratory quotient (RQ), either in the fasting state or in the fed state. These results show that in obese subjects dFE increases energy expenditure in the post-absorptive state, as well as after the ingestion of food.

Up until now, conflicting results have been reported on the association between serum cholesterol and risk of breast cancer in women.

Samples of 38-year-old women were randomly selected from five European centers: Ede (The Netherlands), Warsaw (Poland), Gothenburg (Sweden), Verona (northern Italy), and Afragola (Naples-southern Italy). In total, 452 healthy women were studied. Anthropometric measurements were taken by one operator in each country after common training of all operators and blood parameters of all women were determined in one laboratory. Body mass index (BMI) was different among centers, mainly due to the higher values in southern Italy. Women from southern Europe had more central fat distribution than women from north European centers. Fasting serum insulin was higher in women from Poland and The Netherlands than in the other three centers. After adjustment for BMI, fasting insulin was significantly related to subscapular skinfold, subscapular to triceps skinfold ratio, waist circumference, and waist to thigh circumference ratio, although the partial correlations varied somewhat between the centers. In the pooled data, waist circumference showed the highest correlations with fasting serum insulin when adjusted for BMI. Fasting serum insulin showed significant partial correlations, adjusted for BMI, with lipid profile and blood pressure only in women from the two Italian centers. In the pooled data, fasting serum insulin was significantly positively correlated with serum triglycerides and total cholesterol and negatively to high-density lipoprotein (HDL) cholesterol and HDL/total cholesterol, independently of BMI and waist circumference. While blood pressure was not related to insulin in the pooled women, when adjusted for BMI and waist circumference; here as well, there were some differences in relationships between the centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating concentrations of albumin and the labile proteins prealbumin (PA) and retinol-binding protein (RBP) were evaluated over 20 d in five groups of obese patients. The patients were given four types of very-low-calorie diets (VLCDs) (less than 500 kcal/d) that provided different amounts of protein or carbohydrate (CHO) plus protein and a conventional 1200-kcal/d hypocaloric diet. Serum albumin concentrations did not vary significantly during any of the diets whereas PA and RBP remained unchanged only during the conventional 1200-kcal/d diet. Similar and significant decreases of serum PA and RBP were observed during the VLCDs studied. The molar ratio of RBP to PA did not vary during dieting. Thus, when less than 500 kcal/d are given, changes of serum short-half-life visceral proteins are not affected by either the addition of CHO to protein or the changes in protein intake. Moreover, serum albumin concentration and RBP/PA do not vary during VLCDs.