BACKGROUND The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma gene has been associated in some, but not all, studies with lower body mass index (BMI) and improved insulin sensitivity; how an altered transcriptional activity of PPARgamma2 could influence insulin sensitivity is currently unclear. The free fatty acids (FFAs) released from adipose tissue triglycerides via lipolysis are key mediators of impaired insulin sensitivity; however, no study has described the relationship of the Pro12Ala mutation with circulating levels of FFAs under physiological conditions.OBJECTIVE To investigate in a population-based sample of Caucasians the relation of the Pro12Ala polymorphism with plasma concentrations of FFAs and other markers of lipid and glucose metabolism described as components of the insulin resistance syndrome.SUBJECTS Four hundred and thirty-eight nondiabetic employees of the Italian Telephone Company, aged 35-65 years, randomly selected from a total population of 3900 participants in a company-sponsored health screening.MEASUREMENTS The Pro12Ala polymorphism of the PPARgamma was studied together with plasma FFAs, insulin, glucose, triglycerides, high density lipoprotein (HDL) cholesterol, blood pressure and anthropometry. The Homeostatic Model Assessment (HOMA) index was calculated as a measure of insulin resistance.RESULTS Carriers and noncarriers of the Pro12Ala polymorphism showed very similar circulating levels of FFA (0.46 +/- 0.2 vs. 0.47 +/- 0.2, NS); plasma glucose, triglycerides, HDL cholesterol and blood pressure were also similar in the two groups with or without the polymorphism. To allow for the possible confounding effect of obesity, a separate analysis was conducted in overweight (BMI greater than or equal to 25 kg/m(2)) and normal-weight people (BMI < 25 kg/m(2)). Circulating plasma FFA concentrations, as well as triglycerides, blood pressure and HOMA, were significantly higher in overweight than normal-weight, as expected, but no significant differences were detected between carriers and noncarriers of the Pro12Ala polymorphism within each BMI group (0.49 +/- 0.47 +/- 0.2, NS, in overweight and normal-weight, respectively). The Pro12Ala polymorphism was also analysed across increasing quartiles of FFA concentrations and no relationship was observed between the frequency of the polymorphism and FFA values (overall &chi;(2) = 0.48, NS).CONCLUSION This study does not show any relationship between the Pro12Ala polymorphism of the PPAR&gamma; gene and fasting FFAs in the general population. The possibility of a different handling of FFAs under different conditions (i.e. postprandial) cannot be excluded and remains to be explored.

OBJECTIVE: To explore the association of the Pro12Ala mutation in the peroxisome proliferator-activated receptor γ2 with severe obesity and the features of the metabolic syndrome in a population-based sample of Caucasians. PARTICIPANTS AND METHODS: The study is based on a case–control design: 95 non-diabetic severely obese (body mass index, BMI>35 kg/m 2 ) cases and 280 normal weight (BMI<25 kg/m 2 ), age- and sex-matched controls selected from the same population were studied. Height, weight, waist circumference, as well as blood pressure were measured according to a standard protocol. BMI at age 25 y was calculated on the basis of current height and reported weight at age 25 y Biochemical measurements included fasting glucose, triglycerides, high-density lipoprotein cholesterol and insulin. DNA analysis was conducted by PCR and gel electrophoresis. RESULTS: Age and gender distribution were similar in obese and normal weight participants. The percentage of people with the Pro12Ala mutation was not significantly different in obese or normal weight participants (20% and 15%, respectively; P =0.32). Conversely, in obese participants with obesity starting in early adulthood (ie with BMI at age 25 above 26.9 kg/m 2 which represents the median of the whole obese group), the Pro12Ala mutation was observed significantly more frequently than in the normal weight controls (29% vs 15%; chi square=4.5, P <0.05; odds ratio 2.4; 95% CI 1.03–5.36). No association of the Pro12Ala variant with any of the component of the metabolic syndrome measured in the study was observed in either obese, juvenile obese or normal weight participants. CONCLUSIONS: Results of this study indicate that the Pro12Ala mutation does not play a major role as a determinant of severe obesity and/or features of the metabolic syndrome in the general population. However, this mutation may be of greater importance as a contributor to early onset obesity.

Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by postnatal growth failure, mental retardation and otherwise clinically heterogeneous features which commonly include cutaneous photosensitivity. Cultured cells from sun-sensitive CS patients are hypersensitive to ultraviolet (UV) light and, following UV irradiation, are unable to restore RNA synthesis rates to normal levels. This has been attributed to a specific deficiency in CS cells in the ability to carry out preferential repair of damage in actively transcribed regions of DNA. We report here a cellular and molecular analysis of three Italian CS patients who were of particular interest because none of them was sun-sensitive, despite showing most of the features of the severe form of CS, including the characteristic cellular sensitivity to UV irradiation. They all were altered in the CSB gene. The genetically related patients CS1PV and CS3PV were homozygous for the C1436T transition resulting in the change Arg453opal. Patient CS2PV was a compound heterozygote for two new causative mutations, insertions of an A at position 1051 and of TGTC at 2053, leading to truncated proteins of 367 and 681 amino acids. These mutations result in severely truncated proteins, as do many of those that we previously identified in several sun-sensitive CS-B patients. These observations confirm that the CSB gene is not essential for viability and cell proliferation, an important issue to be considered in any speculation on the recently proposed additional function of the CSB protein in transcription. Our investigations provide data supporting the notion that other factors, besides the site of the mutation, influence the type and severity of the CS clinical features.

OBJECTIVE: To prospectively evaluate progression to diabetes in individuals with impaired glucose regulation as defined according to fasting glucose alone or an oral glucose tolerance test (OGTT) (i.e., both fasting and postload glucose) to compare the ability of these two screening methods to identify people at high risk of developing diabetes. RESEARCH DESIGN AND METHODS: A working population of 1,245 nondiabetic telephone company employees aged 40-59 years was studied by OGTT in 1980. Participants were classified according to baseline fasting glucose only (as encouraged by the American Diabetes Association [ADA]) or OGTT (as recommended by the 1998 World Health Organization [WHO] consultation). Progression to diabetes was evaluated 11.5 years later according to the 1997 ADA criteria of a fasting plasma glucose level > or =7.0 mmol/l. RESULTS: With the use of the OGTT, baseline prevalence of impaired glucose regulation was substantially higher than that with fasting glucose alone (7.2 vs. 3.2%); the two groups only overlap for 40.9% of the cases because a fairly large number of people with postload hyperglycemia (59.1%) have normal fasting glucose. Progression to diabetes in participants with normal fasting glucose and postload hyperglycemia is significantly more frequent than that of people with normoglycemia (32.5 vs. 7.2%; P < 0.001) and not significantly different from that of people with both fasting and postload hyperglycemia (i.e., 44.0%). However, the former are not identified as being at unusually high risk of diabetes unless an OGTT is performed. When the use of fasting glucose alone or OGTT was validated as a marker of progression to diabetes, sensitivity was substantially higher for the OGTT (33.3 vs. 9.0%) without major differences in specificity (92.6 vs. 97.0%). CONCLUSIONS: These data (the only data so far available in Caucasians) support the viewpoint that for the identification of people at high risk of diabetes, the use of the OGTT should be maintained.

The aim of our study was to evaluate, in patients with Type 2 diabetes mellitus (T2DM): 1) the metabolic response to a meal rich in resistant starch (RS); 2) the effects of consumption of RS on the metabolic response to the subsequent meal. The study was randomized and placebo-controlled. Sh men and 4 women with T2DM, age 50 +/- 2 yr (Mean +/- SE), BMI 27 +/- 0.9 kg/m(2), duration of diabetes 6 +/- 1 Yr; fasting plasma glucose 8.49 +/- 0.21 mmol/l, treated with diet alone or diet + sulphonylurea, participated in the study. After a 12-hour overnight fast, the patients consumed, on different days and in random order, two meals with similar composition (protein 15%, fat 30%, carbohydrate 55%, fiber 3 g, kcal 797) but different in RS content (16 vs 1 g). Four hours after the first meal? patients were given a second meal, which was the same, independently of the first meal (protein 15%, fat 30%, carbohydrate 55%, fiber 3 g, kcal 593). Blood samples were collected in the fasting state and every hour for 4 hr after each meal, for measurement of plasma glucose, insulin, triglycerides and NEFA. Blood glucose response was lower after the high RS than after the low RS meal (-32%, f = 5.00; p < 0.03). Also, the triglyceride response was lower after the RS-rich meal (-26%, f = 4.96; p < 0.03. Conversely plasma NEFA and insulin concentrations were similar after the two meals. Consumption of RS had no effect on the subsequent meal; in fact, there were no differences in plasma glucose, insulin, NEFA or triglyceride responses between the standard meals consumed 4 hours after either the high RS or the low RS meal. In conclusion, RS consumption improves the plasma glucose and triglyceride responses to a meal. (C) 1998, Editrice Kurtis.

We describe a case of congenital non-obstructive dilatation of the hepatic bile ducts (Caroli disease). The accuracy of ultrasound for the diagnosis of this syndrome is pointed out. Ultrasound scan can be carried out easily and with a remarkable imaging precision. The ultrasonographic patterns consist of both evident dilatation of the ducts and characteristic protrusions connecting the ductal walls to intraluminal portal branches (bridging). These sonographic findings confirm the etiopathogenetic hypothesis according to which Caroli disease is a result of the blockage of the bile ducts development. Moreover, we underline the efficacy of ursodeoxycholic acid in the treatment of the chronic cholestasis, always present in this disease.

We describe a case of congenital non-obstructive dilatation of the hepatic bile ducts (Caroli disease). The accuracy of ultrasound for the diagnosis of this syndrome is pointed out. Ultrasound scan can be carried out easily and with a remarkable imaging precision. The ultrasonographic patterns consist of both evident dilatation of the ducts and characteristic protrusions connecting the ductal walls to intraluminal portal branches (bridging). These sonographic findings confirm the etiopathogenetic hypothesis according to which Caroli disease is a result of the blockage of the bile ducts development. Moreover, we underline the efficacy of ursodeoxycholic acid in the treatment of the chronic cholestasis, always present in this disease.

The association between osteopetrosis and renal acidosis is not accidental, but represents a well-known syndrome with autosomal recessive transmission, due to carbonic anhydrase II(CA II) deficiency. The disease is extremely rare (only few reports in the literature). The diagnosis is confirmed by CA II erythrocyte assay. However, this finding is not essential when the clinical picture is complete, as in the case reported in this paper, which presents a patient with osteopetrosis, proximal tubular acidosis, intracranial calcifications, psychomotor retardation and short stature. Prenatal diagnosis will rely on the genetic study of DNA by molecular probes, since it is already well-known that the coding gene for CA II is on the long arm of chromosome 8 (8q22).

The authors describe a patient with stenosis of the renal artery undergoing bilateral kidney autotransplantation and reconstruction of the aorta with autologous saphena. This study also provides a general evaluation of renovascular hypertension incidence, etiopathogenesis, symptomatology, diagnostic criteria, therapy. The presence of a diastolic pressure > 110 mmHg, with normal creatinin levels and urinalysis results, is very significant and leads to invasive investigations. Site and size of the anatomic anomaly are evaluated by arteriography. Surgery is the treatment of choice.

We report two cases (F. 11 years, M. 7 years) with juvenile fibro-myalgic syndrome, diagnosed because of the presence of musculo-skeletal pain, tender points and associated symptoms, and after exclusion of any other known etiology. Both patients improved after treatment with antidepressant serotoninergic (amitriptyline, trazodone).

We present a case of two twins, admitted to our department at the age of 9 years and 9 months for poor stature-ponderal growth. Hematochemical tests showed hypokalemia, hypomagnesemia, metabolic alkalosis, renin increase, normal aldosterone values, hypocalciuria. Arterial pressure values were normal in both patients. Renal hypokalemia with metabolic alkalosis was hypothesized and therefore tubular functions during diuresis induced by intravenous 5% dextrose in water were evaluated and fractionated tubular resorption values of chlorides were identified. The two patients presented many characteristics typical of Bartter syndrome (suggestive facies, short stature, hypokalemia, metabolic alkalosis, renin increase, decreased chloride resorption) and of Gitelman syndrome (late onset, few symptoms, hypomagnesemia, hypocalciuria, normal renal concentration). The definition "Bartter-like syndrome" seems to be more suitable for these patients, since it can include all the clinical characteristics and biochemical anomalies observed.

It is common knowledge that the association of thrombocytopenia and radius aplasia, familiar as TAR syndrome, is not fortuitous, but genetically determined as autosomic recessive trait. However, other hypotheses of genetic transmission must be considered. The description of a new case gives us the cue for reviewing the literature and arguing about the pathogenesis, the incidence of the syndrome features, its prognosis and the therapeutic devices. In order to have a better diagnosis, the TAR syndrome is confronted with other pathologies causing limb malformations.

The association of de Toni-Debré-Fanconi syndrome with alteration of galactose metabolism and glycogen hepatic storage, before further clarification, is defined as Fanconi-Bickel syndrome. The Authors present a case in which the alterations in galactose metabolism typically do not affect the enzymes responsible for galactosemia. In such patients a recognised enzymatic defect glycogenosis is not involved and glycogen storage in the liver can be a secondary phenomenon, which can increase, differing according to each subject. Liver biopsy to detect storage can be avoided when all the other diagnostic criteria are observed.

The study assessed the value of anti-gliadin antibodies (AGA) as a diagnostic test for celiac disease (CD) by examining 219 children: 57 were affected by malabsorption syndrome and underwent the first duodenojejunal biopsy; 83 underwent a secondary diagnostic phase for CD; 44 underwent a challenge test; 35 controls. Duodenojejunal biopsy was performed in all subjects in the three stages of diagnosis for CD. By comparing AGA levels and on the basis of histological tests of duodenojejunal mucosa it is possible to confirm the reliability of the method as a screening test for use in subjects whose clinical symptoms suggest CD. AGA are however less reliable in the second and third stages, that is to say in the follow-up of CD, since they do not always reflect the conditions of intestinal mucosa.

Hereditary ataxias form a group of diseases hard to classify, the etiology of which has been determined only as regards some forms. The problem is also that, besides some "typical" and easily classifiable forms, threadbare, incomplete or "transitional" ones do exist, which are not easily classified. The observation of two brothers, both "atypical" in some respects, offered the opportunity to dwell upon the most well-known heredofamilial ataxias, pointing out their most characteristic traits. According to the Authors, the classifications suggested to date are certainly provisional and subject to notable changes as knowledge progresses. Maybe molecular genetics will be determining in this respect.