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Contains fulltext : 125353.pdf (Publisher’s version ) (Open Access) BACKGROUND: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of beta-cell function and metabolic control was examined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve beta-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 microg calcitriol per day or placebo (1:1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P

Acute lymphoblastic leukemia (ALL) is the most common subtype of leukemia in children. Although ALL and type 1 diabetes appear to be biologically unrelated, there are common threads in both epidemiology and etiology. Rising incidence rates of both ALL (1) and type 1 diabetes (2) observed over recent decades in many Western countries seem to support common etiological factors (3). In the current study, we report on diabetes-related autoantibodies (Abs) in a group of patients with ALL. Thirty-four consecutive children (19 males and 15 females, mean age 6.2 ± 4.6 years) were referred to our institution in 2004 for newly diagnosed ALL. Patients were tested for Abs to islet and thyroid antigens. After the initial investigation and treatment, 31/34 (91%) patients (3 died in the mean time) were followedup for 6 years to evaluate the evolution of the autoimmune markers and progression toward type 1 diabetes. Glutamic acid decarboxylase (GAD) Abs by direct …

The main objective of this study is to assess the course of peroneal mononeuropathy (PM). The study design includes Clinical and Prospective study. The setting involves neurophysiological Service. From November 2002 to January 2004, we enroled 69 consecutive patients and prospectively followed up 49 patients with multiple measurements. Comparison was made between follow-up and baseline values, and baseline factors were used to predict the PM evolution in multiple regression analysis. At follow-up, we observed a significant improvement of all clinical, neurophysiological and disability measurements, and physical aspects of quality of life (QoL). Greater muscle strength of tibialis anterior and higher conduction velocity of peroneal nerve at baseline were seen to be positive prognostic factors. A better evolution of mental aspects of QoL was observed in the subacute group and in younger patients, while a better physical evolution in QoL was observed in women. Rehabilitation is ambiguously associated with a better Deambulation Index but lower ratings in mental aspects of QoL. In conclusion, PM shows a positive spontaneous course and rehabilitation seems to help the recovery of deambulation. Further studies on the effects of conventional rehabilitation are needed.

Background A number of recent studies underline the importance of vitamin D in the pathogenesis of Type 1 diabetes (T1D). Aims The aim of this study was to investigate whether supplementation with the active form of vitamin D (calcitriol) in subjects with recent-onset T1D protects residual pancreatic β-cell function and improves glycaemic control (HbA1c and insulin requirement). Methods In this open-label randomized trial, 70 subjects with recent-onset T1D, mean age 13.6 years ± 7.6 sd were randomized to calcitriol (0.25 µg on alternate days) or nicotinamide (25 mg/kg daily) and followed up for 1 year. Intensive insulin therapy was implemented with three daily injections of regular insulin + NPH insulin at bedtime. Results No significant differences were observed between calcitriol and nicotinamide groups in respect of baseline/stimulated C-peptide or HbA1c 1 year after diagnosis, but the insulin dose at 3 and 6 months was significantly reduced in the calcitriol group. Conclusions At the dosage used, calcitriol has a modest effect on residual pancreatic β-cell function and only temporarily reduces the insulin dose.

Four samples of patients (fulfilling at the index episode, respectively, Research Diagnostic Criteria for schizoaffective disorder manic type, schizoaffective disorder depressed type, manic disorder and major depressive disorder) were followed up for 3 years. At the end of the follow-up period, no significant difference with respect to the mean scores on the Disability Assessment Schedule (DAS) and on the Strauss-Carpenter Outcome Scale was observed between schizomanics and manics (although the global outcome was slightly poorer in the former group). In contrast, significant differences between schizodepressives and depressives were found both on some DAS subscales (the schizodepressives were more socially withdrawn, had less social contacts and poorer work performance) and on the Strauss-Carpenter Outcome Scale (the mean total score and the mean scores on the items "social contacts" and "employment" were significantly lower in schizodepressives). The most frequent pattern of course in patients diagnosed cross-sectionally as schizomanic was a bipolar one. Some patients had only recurrent schizomanic episodes and others more an alternance of schizomanic and schizophrenic episodes. In patients diagnosed cross-sectionally as schizodepressives, the most frequent pattern of course was that characterized by recurrent schizodepressive episodes. In some patients an alternance of schizodepressive and depressive or schizodepressive and schizophrenic episodes was observed. These data confirm that patients diagnosed cross-sectionally as schizoaffective represent a very heterogeneous group when they are studied longitudinally, and support the usefulness of a "multiaxial" approach to the classification of schizoaffective disorders, taking into account both cross-sectional symptomatology and clinical course.

Prophylactic use of Lithium salts in patient suffering from cluster headaches has been evaluated looking at the mean number of headache attacks in one critical period and the mean weekly duration of the period itself. These two elements have been compared to those observed on other drugs treatments. Plasma Lithium monitoring has been performed weekly during the trial. Authors discuss the results reported and the hypothetic basis of them.

A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis.We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis.In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years.Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.

Two brothers presented with late-onset cerebellar ataxia and severe dysphonia. Brain MRI showed vermian and hemispheric cerebellar atrophy. Laringofiberscopy revealed laryngeal abductor paralysis in both patients. Neurophysiologic studies showed a pure motor neuropathy. The combined findings and the molecular analysis suggest a new familial disorder. Inheritance is most likely autosomal recessive, but X-linked transmission is also possible.

In liver cirrhosis, the renin-angiotensin-aldosterone system is involved in the pathogenesis of portal hypertension. Its effector, angiotensin II, is generated by angiotensin-converting enzyme (ACE). Serum ACE levels are affected by I/D polymorphism of its gene, with alleles I and D being associated, respectively, with lesser and greater activity of the enzyme. In cirrhotic patients carrying the ACE I allele, an increased risk for gastro-oesophageal varices was observed.The aim of our study was to evaluate whether ACE I/D polymorphism influenced portal pressure.Fifty-one consecutive cirrhotic patients were divided based on ACE genotype (DD, ID, and II). Kidney and liver function tests, upper endoscopy, and hepatic venous pressure gradient measurement (HVPG) were performed in all patients.The presence of the ACE I allele was associated with a higher HVPG value (18.7±6.4 vs 10.3±6.3mmHg; P.001), higher frequency of large gastrooesophageal varices (59.3% vs 25.0%; P.05), and higher frequency of variceal bleeding (63.0% vs 29.2%; P.05). No significant differences were found between patients with and those without the ACE I allele regarding Child-Pugh score, MELD score, ascites, and hepatic encephalopathy.ACE I/D polymorphism seems to influence the severity of portal hypertension and the risk of variceal bleeding in liver cirrhosis, regardless of the severity of liver disease.

Objectives: To analyze a possible association between glutathione-S-transferase T1 (GSTM1) and/or glutathione-S-transferase M1 (GSTM1) polymorphisms and chronic or aggressive forms of periodontitis in a Caucasian ethnic group. Design and methods: Sixty-nine chronic, 14 aggressive periodontitis and 61 controls, deeply analyzed from a clinical point of view, were studied for their GSTM1 and GSTT1 polymorphisms by allelic specific PCR techniques. As a second control group, 64 blood donors were also included. Results: A significant association was found between GSTM1-null genotype and both chronic and aggressive periodontitis. The aggressive forms were associated with the double null GSTM1 and GSTT1 combination. These results were independent of the patients' age, gender, hygienic habits and smoke (evaluated as tobacco smoking yes/no, cigarettes/day and pack years) as confirmed by multivariate logistic regression analysis. Conclusions: The GSTM1-null variant is statistically associated with the two forms of periodontitis, while the aggressive one also presents a second null variant: GSTT1.

Introduction We evaluated the gene expression levels of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha in skeletal muscle samples of patients with gastric cancer and controls. Methods We studied 38 cancer patients and 12 controls who underwent surgery for gastric adenocarcinoma and benign abdominal diseases, respectively. A biopsy specimen was obtained from the rectus abdominis muscle from all participants. The relative gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha was determined by qRT-PCR analysis. Results Atrogin-1 and MuRF1 mRNA expression was similar between cancer patients and controls and was unaffected by the disease stage or the severity of body weight loss. Transcript levels of myostatin and follistatin did not differ between cases and controls and were similar across disease stages and categories of weight loss. Finally, no differences were detected in activin A and inhibin alpha gene expression between cancer patients and controls. Discussion In skeletal muscle, the gene expression of atrogin-1, MuRF1, myostatin, follistatin, activin A, and inhibin alpha is not affected by the presence of cancer. The expression of atrophy-related genes is unaffected by the disease stage and the degree of weight loss. © 2013 Wiley Periodicals, Inc.

Patency of the ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) development represent severe affections for premature newborns, therefore the research of early markers for these two conditions is really important. The aim of this study is to analyze epithelial lining fluid (ELF) Neutrophil-gelatinase-associated lipocalin (NGAL) levels for prediction of lung injury or possible involvement of this molecule in PDA. Only scarce and contrasting results have previously been published in this field. In contrast, this molecule, included in a large macromolecular complex together with matrix metalloproteinase-9 (MMP-9), is considered an acceptable marker of infectious/inflammatory processes, cancer monitoring and induction of apoptotic pathway. NGAL was detected in 28 pre-term newborns by means of a commercially available kit in bronchoalveolar lavage fluid (BALF). The results have been corrected to ELF levels, by the urea method, to eliminate bias due to BALF collection. ELF NGAL levels were found significantly increased both in infants developing BPD or in those affected by PDA. By means of multivariate logistic regression analysis the significances were confirmed after adjusting for possible interfering variables such as gestational age and concomitant presence of both PDA and BPD. Our results stress the involvement of NGAL in the mechanisms leading to BPD and also suggest a possible association with PDA, which is often linked to prematurity and BPD development, probably due to the involvement of inflammatory and angiogenetic processes in both pathologies.

Summary Background Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. Objectives The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. Methods One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. Results All cases and controls were in Hardy–Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0·02) along with Breslow thickness (P = 0·001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. Conclusions Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.

Background Even though the gene encoding for IGF-I is considered of most importance amongst blood pressure-regulating genes in mouse models, little and discordant data are available in literature for what concerns a possible relationship between blood pressure and serum free IGF-I values in humans. In addition, no information is available on type 1 diabetes patients. Aim: Our aim is to analyze the relationship between systolic and diastolic blood pressure and serum free IGF-I and IGFBP-3 levels in subjects suffering from type 1 diabetes. Results: A highly significant inverse correlation was observed between serum free IGF-I levels and both systolic and diastolic blood pressure in subjects affected with type 1 diabetes. Similar but less significant relationships were observed for IGFBP-3, whose levels were also significantly and directly correlated with those of free IGF-I. The correlation between systolic and diastolic blood pressures with free IGF-I and between systolic blood pressure and IGFBP-3 levels were confirmed after adjusting for age, gender, age at diagnosis, disease duration, familial history, HBA1c, and amount of insulin administered by multivariate logistic regression analysis. A decrease in free IGF-I and IGFBP-3 levels, along with increases in blood pressure, significantly influenced the presence of diabetic complications, confirming how these molecules may be considered as severity markers for patients with type 1 diabetes as well as risk factors for altered pressure control linked diseases.