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Biomedical subjects

D Conte

Publications and source records attributed to D Conte.

At least 19 recordsLinked to original sources
PubMed2004

Gallstone disease and related risk factors in a large cohort of diabetic patients.

BACKGROUND AND AIM: The aim of this study of a large cohort of consecutive patients with diabetes mellitus was to investigate the still controversial questions concerning the prevalence and possible risk factors of gallstone disease in diabetics. PATIENTS AND METHODS: We enrolled 1337 consecutive patients (710 males aged 63 +/- 11 years and 627 females aged 65 +/- 11 years), of whom 1235 (92%) had type 2 and 102 (8%) had type 1 diabetes mellitus. The data were statistically analysed using multiple logistic regression analysis. RESULTS: The prevalence of gallstone disease was significantly higher in diabetics than in the general population with comparable characteristics (MICOL study) (332/1337 (24.8%) versus 4083/29684 (13.8%); z = 11.208, P = 0.0001) and this difference maintained its statistical significance even when only the North Italian centers involved in this nation-wide survey were considered (332/1337 (24.8%) versus 2469/18091 (13.6%); z = 11.225, P = 0.0001). A total of 332 diabetics (25%) had gallstone disease: 261 had stone(s) and 71 had previously undergone cholecystectomy for gallstone disease after a diagnosis of diabetes mellitus. The prevalence of gallstone disease was higher in the females (29% versus 22%, P = 0.003), and increased with age (13, 20 and 30% in patients aged < or = 40, 41-65 and > 65 years, respectively; P = 0.001), body mass index (24% in patients with a body mass index of < or = 30 and 30% in those with a body mass index of > 30 kg/m2; P = 0.001) and a positive family history of gallstone disease (31% versus 23%; P = 0.001). Gallstone disease was not significantly related to the type of diabetes, plasma total and HDL cholesterol and triglyceride levels, alcohol intake, smoking habits, physical activity, weight reduction in the last year, the use of oral contraceptives, parity or menopause. At multivariate analysis, increasing age, a higher body mass index and a positive family history maintained their statistical significance. CONCLUSIONS: In patients with type 1 or type 2 diabetes mellitus, the prevalence of gallstone disease was significantly related to age, body mass index and a family history of gallstone disease.

Age Factors↗
PubMed2004

Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly.

OBJECTIVE: Ghrelin, a gut-brain peptide involved in the control of energy homeostasis, affects antero-pituitary and gastro-entero-pancreatic (GEP) hormone secretion in healthy subjects. We aimed to verify whether such hormonal responses are retained in acromegaly, a disease characterized by high GH, subnormal ghrelin and abnormal GEP hormone levels. DESIGN AND METHODS: The effect of ghrelin (3.3 microg/kg given after overnight fasting as an i.v. bolus) on GH, prolactin (PRL), adrenocorticotropin (ACTH), cortisol, insulin, glucose, total somatostatin (SS) and pancreatic polypeptide (PP) circulating levels were evaluated in seven non-diabetic patients with newly diagnosed acromegaly and in nine healthy controls. RESULTS: Ghrelin elicited a prompt, marked increase of serum GH and PRL levels in all normal (from 1.6+/-0.6 to 52.9+/-7.8 and from 9.7+/-0.8 to 24.2+/-4.8 microg/l (means+/-S.E.M.), respectively) and acromegalic subjects (from 11.2+/-4.9 to 91.6+/-21.0 and from 42.9+/-26.1 to 113.8+/-79.0 microg/l, respectively). Both plasma ACTH and serum cortisol levels rose significantly in the controls, whereas the cortisol response was blunted in the acromegalic patients. Glucose levels rose earlier and insulin levels fell later in all subjects, with a significantly greater net insulin decrease in acromegalic than in healthy subjects (-80+/-21 vs -17+/-4 pmol/l, P<0.01). A prompt PP rise and a biphasic SS response occurred in all controls, whereas in the acromegalic group the PP response (from 26.1+/-5.0 to 92.2+/-39.0 pmol/l) and the SS response (from 11.9+/-3.0 to 19.7+/-4.0 ng/l) were quite variable. CONCLUSIONS: Ghrelin affects both pituitary and GEP hormones in acromegalic patients as in normal subjects. These findings suggest that ghrelin actions on the energy balance are mediated by complex interactive endocrine loops that involve also the gut and pancreas.

Acromegaly↗
PubMed2003

A puzzling jaundice.

In an adult beta-thalassaemic patient admitted on account of the sudden onset of nausea, vomiting and biliary pain, the concomitant jaundice was considered "obstructive" on the basis of ultrasonographic evidence of cholecysto-choledocal stones. However, when the patient was re-evaluated it was found that concomitant Gilbert's disease, hepatitis C virus related cirrhosis and dilated cardiomyopathy had a detrimental effect on clinical and laboratory findings.

Aged↗
PubMed2003

Gallbladder motility in obesity, diabetes mellitus and coeliac disease.

We reviewed data on gallbladder motility in obesity, diabetes and coeliac disease. In obesity, a condition characterised by increased risk of gallstone(s), decreased gallbladder motility has heterogeneously been reported as a consequence of the different type of meals used to induce gallbladder contraction, characteristics of the population studied, technique used, and proportion of patients with hyperinsulinaemia. Moreover, recent studies have evaluated the effect of dietary restriction on gallbladder motility in obese patients. A two- to three-fold increase in the risk of cholesterol gallstone(s) has been reported in diabetic patients, mainly in relation to obesity and hypertriglyceridaemia. Furthermore, decreased gallbladder motility has been described and attributed to other factors, including underlying autonomic neuropathy, reduced gallbladder sensitivity to cholecystokinin and/or reduced number of cholecystokinin receptors on the gallbladder wall. Impaired gallbladder motility has been reported also in patients with coeliac disease in relation to reduced secretion of enteric hormones and/or decreased gallbladder sensitivity to them. In particular, untreated coeliacs, when compared to controls, showed low postprandial cholecystokinin and increased fasting somatostatin levels. Interestingly, the correlation between fasting somatostatin levels and gallbladder size has clearly been confirmed in patients affected by somatostatinoma or treated with somatostatin or its analogues. Gallbladder motility can be affected by various clinical conditions, such as obesity, diabetes mellitus and coeliac disease.

Celiac Disease↗
PubMed2003

Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1.

OBJECTIVE: As circulating chromogranin A (CgA) has been claimed to be the best general neuroendocrine marker so far available, we evaluated the usefulness of CgA determination in the clinical assessment of patients with sporadic gastro-entero-pancreatic neuroendocrine tumors (GEP NETs) or multiple endocrine neoplasia type 1 (MEN 1). DESIGN AND METHODS: Plasma CgA levels were measured using a commercial enzyme-linked immunosorbent assay in 61 patients with sporadic GEP NET and in 25 with MEN 1 including 16 with GEP NET. Controls were 50 healthy volunteers, 46 patients with pituitary adenoma and 35 patients with primary hyperparathyroidism. RESULTS: The cutoff value for CgA established in our healthy subjects (as mean+2 s.d.) was 20 U/l. CgA levels were above the normal range in 71/77 patients with sporadic or MEN 1-related GEP NETs (92%), in four out of nine MEN 1 patients without GEP NETs (44%), and only in 22/81 control patients with pituitary or parathyroid disease (27%). Furthermore, CgA levels of over 100 U/l occurred in 36/77 patients with GEP NETs (47%) and only in one patient with a non-functioning pituitary adenoma. In the patients with GEP NETs, both tumor burden and secretory activity affected CgA levels, and successful surgical resection was associated with markedly decreased CgA values. CONCLUSIONS: Plasma CgA was confirmed to be a reliable marker for GEP NETs. Moreover, in MEN 1 patients the finding of very high CgA levels strongly suggests the presence of a GEP NET, as both primary hyperparathyroidism and pituitary adenomas rarely cause marked CgA increases.

Adenoma↗
PubMed2002

High frequency of anti-endomysial reactivity in candidates to heart transplant.

BACKGROUND: A possible link between coeliac disease and dilated cardiomyopathy has recently been suggested. AIMS: . To assess the frequency of anti-endomysial antibodies, the marker for coeliac disease, in patients with different forms of heart failure, and to establish the clinical features of those endomysial antibody positive. SUBJECTS AND METHODS: . A total of 642 consecutive patients entering the waiting list for heart transplantation from 1995 through 1997 were studied. The prevalence of endomysial IgA antibodies, determined by indirect immunofluorescence, was compared to that observed in three surveys conducted in the Italian general population. RESULTS: Of the 642 patients, 12 (1.9%; 95% confidence interval 0.97-3.2) resulted endomysial antibody positive, versus 34/9,720 healthy controls (0.35%; 95% confidence interval, 0.23-0.47), accounting for a relative risk of 5.3 (95% confidence interval, 2.8-10.3). Anti-endomysial antibodies were found in 6/275 patients with dilated cardiomyopathy and 6/367 with other forms of heart failure (2.2% versus 1.6%; 95% confidence interval 0.8-4.7 and 0.6-3.5), with no statistical difference. The 12 endomysial antibody positive patients were leaner (body mass index, 22.0 +/- 1.9 vs 24.2 +/- 3. 1, p<0. 05) than 36 seronegative patients matched for baseline demographics and aetiology of cardiomyopathy No differences were observed as regards clinical, biochemical and echocardiographic features, mortality in waiting list and 2-year post-transplant survival. CONCLUSIONS: Patients with end-stage heart failure are at increased risk for coeliac disease as compared to the general population.

Adult↗
PubMed2001

Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases.

BACKGROUND: The reported prevalence of gallstone disease (GD), defined as current gallstones or previous cholecystectomy for gallstones, in patients with Crohn disease ranges from 13% to 34%. The aim of this study was to characterize the still undefined risk factors of this complication. METHODS: A total of 330 consecutive patients with Crohn disease (189 males and 141 females aged 17-82 years, mean +/- SD age, 41 +/- 14 years) underwent liver ultrasonography. RESULTS: A diagnosis of GD was made in 78 patients (24%), 54 with current gallstones and 24 who had undergone previous cholecystectomy. Its frequency was comparable in males and females (23% vs 25%), but was significantly associated with age (P =.001), being 13%, 36%, and 51% in patients aged 44 years and younger, 45 to 59 years, and 60 years and older, respectively (P =.001). Its prevalence significantly differed according to the site of the disease at diagnosis (P =.02) and was unrelated to disease duration. Gallstone disease was more frequent in patients who had undergone surgery (34% vs 14%; P =.001) and was significantly associated with the number (P =.001) and site of bowel resections (P =.001), increasing from 28% in the patients who had undergone 1 resection to 53% in those having had 2 or more resections (P =.005) and being significantly higher in patients with a resection involving the ileocecal region. Multivariate analysis showed that age; site of disease at diagnosis; and the presence, number, and site of bowel resections were significantly related to GD. CONCLUSIONS: In patients with Crohn disease, the frequency of GD is significantly higher than that reported in the general population with comparable characteristics (z = 5.04, P<.001). Age; site of disease at diagnosis; and the history, number, and site of bowel resections are independently associated with GD.

Adolescent↗
PubMed2001

Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing.

RNAi is a gene-silencing phenomenon triggered by double-stranded (ds) RNA and involves the generation of 21 to 26 nt RNA segments that guide mRNA destruction. In Caenorhabditis elegans, lin-4 and let-7 encode small temporal RNAs (stRNAs) of 22 nt that regulate stage-specific development. Here we show that inactivation of genes related to RNAi pathway genes, a homolog of Drosophila Dicer (dcr-1), and two homologs of rde-1 (alg-1 and alg-2), cause heterochronic phenotypes similar to lin-4 and let-7 mutations. Further we show that dcr-1, alg-1, and alg-2 are necessary for the maturation and activity of the lin-4 and let-7 stRNAs. Our findings suggest that a common processing machinery generates guide RNAs that mediate both RNAi and endogenous gene regulation.

Animals↗
PubMed2001

Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients.

We evaluated whether the amount of circulating DNA in plasma could discriminate between lung cancer patients and healthy individuals and whether it is related to disease progression, and we analyzed the kinetics of plasma DNA in disease-free, surgically resected patients. Plasma DNA quantification and analysis of microsatellite alterations were performed in a consecutive series of 84 patients with non-small cell lung cancer, who were studied during follow-up, and 43 healthy controls. In patients, the mean values of plasma DNA concentration were higher than in controls even considering stage Ia patients. Sensitivity and specificity estimates were calculated as the area under the receiver operating characteristic curve (AUC-ROC) curve and showed a value of 0.844. Variations in DNA level and in microsatellite changes correlated with the clinical status of 38 patients monitored during follow-up. The data suggest that quantification and molecular characterization of plasma DNA in lung cancer patients are valuable noninvasive diagnostic tools for discriminating patients from unaffected individuals and for detecting early recurrence during follow-up.

Adult↗
PubMed2001

Thymocyte-targeted overexpression of xiap transgene disrupts T lymphoid apoptosis and maturation.

The X-linked inhibitor of apoptosis (XIAP) and other members of the inhibitor of apoptosis (IAP) family can suppress apoptosis induced by a diverse variety of triggers. Functional studies done to date have focused on tissue culture models and adenovirus overexpression of XIAP and other IAP proteins. Here we report the phenotype of an engineered transgenic mouse overexpressing a human IAP, as well as assessing the long-term consequence of IAP overexpression. We document the relative protein expression levels of the endogenous mouse homologue to XIAP, mouse inhibitor of apoptosis (MIAP 3), within thymocyte and T cell subpopulations. The consequence of lymphoid-targeted overexpression of XIAP in transgenic mice suggests a physiological role for the endogenous protein, MIAP3. Xiap-transgenic mice accumulated thymocytes and/or T cells in primary and secondary lymphoid tissue, T cell maturation was perturbed, and transgenic thymocytes resisted a variety of apoptotic triggers both in vitro and in vivo. These observations imply a possible key function for the intrinsic cellular inhibitor XIAP in maintaining the homeostasis of the immune system.

Animals↗
PubMed2001

"Hepatitic flare", asthenia, peripheral polyneuropathy and diffuse liver steatosis in a hepatitis C virus asymptomatic chronic carrier.

In July 2000, a 62-year-old female, with a ten-year history of chronic hepatitis C virus infection and persistently normal aspartate amino-transferase and alanine aminotransferase levels, presented with asthenia, weight loss, peripheral polyneuropathy and increased levels of aspartate aminotransferase (8 times upper normal limit), alanine aminotransferase (10 times upper normal limit) and gamma glutamyl-transferase (6 times upper normal limit). The ultrasound findings were consistent with massive liver steatosis. The patient had been previously diagnosed elsewhere as having hepatitis C virus-related "hepatitic flare" with neurological involvement related to concomitant mixed type-III cryoglobulinaemia. However intense exposure to trichloroethylene since April 2000 was revealed and liver histology was fully consistent with non-alcoholic steatohepatitis. The pathogenetic role of the solvent was definitely supported by the complete clinical and biochemical remission within six months of trichloroethylene withdrawal.

Asthenia↗
PubMed2001

Clinical course of pregnant women with chronic hepatitis C virus infection and risk of mother-to-child hepatitis C virus transmission.

As far as concerns chronic hepatitis C virus infection in pregnant women, different points remain to be elucidated, such as the clinical course, the rate of mother-to-child hepatitis C virus transmission and, in particular, its route and the possible risk factors. This review aimed to analyse current data on the prevalence of chronic hepatitis C virus infection in pregnant women and its relationship with risk factors, the rate of mother-to-child hepatitis C virus transmission and the factors possibly involved, particularly the maternal hepatitis C virus viral load and the human immunodeficiency virus coinfection, and the type of delivery and feeding. Finally, the appropriate timing for HCV-RNA testing in newborns has been reviewed.

Breast Feeding↗
PubMed2001

Identification of XAF1 as an antagonist of XIAP anti-Caspase activity.

The inhibitors of apoptosis (IAPs) suppress apoptosis through the inhibition of the caspase cascade and thus are key proteins in the control of cell death. Here we have isolated the protein XIAP-associated factor 1 (XAF1) on the basis of its ability to bind XIAP, a member of the IAP family. XIAP suppresses caspase activation and cell death in vitro, and XAF1 antagonizes these XIAP activities. Expression of XAF1 triggers a redistribution of XIAP from the cytosol to the nucleus. XAF1 is ubiquitously expressed in normal tissues, but is present at low or undetectable levels in many different cancer cell lines. Loss of control over apoptotic signalling is now recognized as a critical event in the development of cancer. Our results indicate that XAF1 may be important in mediating the apoptosis resistance of cancer cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Reduced serum ceruloplasmin levels in hereditary haemochromatosis.

As ceruloplasmin (Cp) seems to be involved in iron mobilization, serum Cp levels were measured in 35 patients with hereditary haemochromatosis (HH), 12 with acquired iron overload (AIO) and 36 healthy subjects. Cp was lower in HH patients than in controls (P < 0.001); no difference was found between untreated HH patients and those on a phlebotomy programme (P = 0.07) and between the HH patients carrying the normal and the mutated alleles of the HFE gene (P = 0.8). Cp levels in AIO subjects were significantly higher than in HH patients (P < 0.004) and similar to those of controls (P = 0.2). No differences in albumin, alpha1 acid glycoprotein and copper serum levels were observed in the three groups.

Adult↗
PubMed2001

Duodenal expression of a putative stimulator of Fe transport and transferrin receptor in anemia and hemochromatosis.

BACKGROUND & AIMS: Stimulator of Fe Transport (SFT) and transferrin receptor (TfR) are proteins involved in iron transport. This study evaluated iron metabolism protein expression in duodenal biopsy specimens from controls and patients with abnormal iron metabolism. METHODS: Twelve controls, 8 patients with iron deficiency anemia, 7 with HFE-related hemochromatosis, and 6 with non-HFE-related iron overload were studied. Immunohistochemistry was performed on duodenal biopsy specimens with anti-TfR and anti-SFT antibodies which recognize a putative stimulator of Fe transport of ~80 kilodaltons. RESULTS: In controls, the putative stimulator of Fe transport was expressed in the middle and distal part of the villi in the subapical cytoplasmatic region. Its expression increased in anemics and, to a lesser degree, in HFE-related hemochromatotics, whereas it was reduced in patients with non-HFE-related iron overload. TfR expression showed a crypt-to-tip gradient in controls, but not in anemics, in whom it was uniformly overexpressed. TfR expression was intermediate in HFE-related hemochromatotics and similar to controls in non-HFE-related iron overload. CONCLUSIONS: Expression of the putative stimulator of Fe transport and TfR increases in iron deficiency. Increased expression of both proteins is present only in HFE-related hemochromatotics suggesting that other factors may be involved in determining non-HFE-related iron overload phenotype.

Adult↗
PubMed2001

Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron-related chronic liver disease.

It has been suggested that excess iron may facilitate the occurrence of cancer. Patients with hereditary hemochromatosis (HH) are at high risk of developing liver cancer, and studies of limited series reported a high frequency of nonhepatic cancers. To verify whether patients with HH are at higher risk of liver cancer and other malignancies as compared with patients with non-iron-related chronic liver disease (CLD), we analyzed the occurrence of neoplasms in 230 patients with HH and 230 with non-iron-related CLD. The patients were matched by sex, age, duration of follow-up (+/-5 years), and severity of liver disease. On enrollment, the following variables were considered: hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol abuse, smoking, and a family history of cancer (first-degree relatives). The diagnosis of primary cancers was confirmed by histology. During the follow-up, hepatocellular carcinoma (HCC) developed in 49 and 29 patients (all cirrhotic patients) with HH and non-iron-related CLD, respectively, with a relative risk of 1.8 (95% confidence interval [CI] 1.1-2.9); nonhepatic cancers occurred in 20 and 11 patients, respectively, with a relative risk of 1.8 (95% CI 0.8-4). Four patients with HH and 1 with non-iron-related CLD developed 2 different primary cancers during follow-up. The risk of cancer after adjustment for alcohol abuse, smoking, and family history of cancer was 1.9 (95% CI 1.1-3.1) in the patients with HH. In conclusion, patients with HH are at high risk of both liver cancer and other malignancies, which should be carefully sought during follow-up.

Adult↗