Administration of vitamin D and high dose of omega 3 to sustain remission of type 1 diabetes.

OBJECTIVE: Two cases of Type 1 Diabetes (T1D) in pediatric subjects treated with supplementation with high dose vitamin D and omega 3 are reported. A similar pattern of remission of the disease was observed, resulting in restoration and subsequent persistence of optimal metabolic control, one and two years after T1D onset. Minimal basal insulin administration (0.1 IU/kg/die) in a single evening injection was required. The immunomodulatory and anti-inflammatory properties of the supplements were likely contributing to the observed effect. Similarities in genotyping and autoantibody patterns in these two cases could be of assistance to identify which subjects with T1D could benefit from this supplemental therapy. High dose vitamin D and omega 3 could be of assistance in childhood T1D therapy, to prolong preservation of endogenous insulin secretion in the absence of side effects. We do not know how long the state of remission can last, but these initial results are promising and represented a significant benefit for the two pediatric subjects treated. Larger controlled studies will determine the long-term effect of this proposed supplementation and its possible cost-benefits, including reduction of hypoglycemic episodes and complications.

Can Type 1 diabetes progression be halted? Possible role of high dose vitamin D and omega 3 fatty acids.

In Type 1 Diabetes (T1D) in children, close to the onset the requirements of insulin are often reduced. This represents a transient recovery of endogenous insulin secretion named "honeymoon" because transient and followed by a progressive decline in C-peptide secretion. This case report describes the effect of administration of high dose vitamin D and Ω-3 fatty acids on T1D progression in a 8-year-old child. At today after one year and a half from the onset of T1D, the subject shows a near-normal blood glucose with the administration of 1.5-2 UI of insulin once a day. Thus this report may be of assistance to design additional studies to determine and validate the effect of administration of vitamin D and Ω-3 fatty acids on the progression of T1D.

Vitamin D status and type 1 diabetes in children: evaluation according to latitude and skin color.

AIM: We aim to investigate vitamin D (25OHD) levels in children with or without type 1 diabetes (T1D) according to latitude and skin color. METHODS: We compared 25OHD levels in children with T1D living in Piedmont, of Caucasian or Moroccan origin, with healthy control subjects matched for age and ethnicity. Data of resident children in Morocco, with and without T1D, were used for comparison. RESULTS: Caucasian (21.4±1.5 vs. 24.0±0.5 ng/mL, P<0.05) and Moroccan children with T1D (12.0±2.6 vs. 17.1±1.7 ng/mL, P<0.05) living in Piedmont had lower 25OHD levels than their counterparts without diabetes. Moroccan children living in Morocco with and without T1D had similar 25OHD levels. Vitamin D deficiency was associated with T1D in Caucasian and Moroccan children living in Piedmont (OR: 1.720, CI95% 1.034-2.860, P<0.03), CONCLUSION: Lower vitamin D levels were associated with T1D in Piedmont. Further studies are necessary to explain a possible relationship between vitamin D and T1D.

Lipid profile and nutritional intake in children and adolescents with Type 1 diabetes improve after a structured dietician training to a Mediterranean-style diet.

AIM: To evaluate if nutritional intakes and lipid profile fulfill international guidelines and recommendations before and after a structured dietician training to a Mediterranean- style diet in an Italian pediatric population with Type 1 diabetes. METHODS: A 6-month prospective cohort study. Baseline and after-intervention nutritional intakes, lipid profile, glycated hemoglobin (HbA(1c)), and clinical parameters of 96 children and adolescents with Type 1 diabetes were assessed. A comparative computerized system which was approved and validated by the Italian Diabetologist Association was used to define the amounts of nutrients. RESULTS: At baseline mean daily dietary intakes of carbohydrates, proteins, and lipids were respectively (mean ± SEM) 51.8 ± 0.5, 15.9 ± 0.2, 33.8 ± 0.6%, with a contribution of cholesterol of 248.7 ± 12.5 mg/day. Fiber assumption was 18.0 ± 0.4 g/day. The 64.5% and 29.1% (p<0.0001) of subjects had at least one lipid parameter higher than 75(th) and 95(th) percentiles, respectively, of selected cut points (American Diabetes Association guidelines for total and LDL-cholesterol and American Academy of Pediatrics standards for HDL-cholesterol and triglycerides). Six months after the dietician intervention, dietary lipids and cholesterol decreased (p<0.0001) while fibers (p<0.0001) increased. LDL-cholesterol, non-HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios significantly decreased (p<0.001) with a reduction of rate of subjects with at least one pathological lipid parameter (p<0.01) independently by weight and glucose control. CONCLUSIONS: Italian pediatric subjects with Type 1 diabetes present a balanced diet with exception of lipids intake and a suboptimal lipid profile. A structured dietician training to a Mediterranean-style diet improves the quality of nutrient intakes being followed by a reduction of LDL-cholesterol, non- HDL-cholesterol, and total cholesterol:HDL-cholesterol ratios.

The osteopontin gene +1239A/C single nucleotide polymorphism is associated with type 1 diabetes mellitus in the Italian population.

Secreted phosphoprotein 1, also known as Osteopontin (Opn), is a proinflammatory cytokine involved in the TH1 response and is highly expressed in the islets and pancreatic lymph nodes of non-obese diabetic mice before the onset of diabetes. In humans, typing of the +1239A/C single nucleotide polymorphism (SNP) in the 3UTR of the Opn gene (SPP1) showed that +1239C carriers displayed higher Opn serum levels than +1239A homozygotes and a higher risk of developing autoimmune/lymphoproliferative syndrome, multiple sclerosis, and systemic lupus erythematosus. The aim of this work is to evaluate whether +1239A/C is also associated with type 1 diabetes mellitus (T1DM). We typed +1239A/C in an initial cohort of 184 T1DM patients and 361 controls, and confirmed our data in a second cohort of 513 patients and 857 controls. In both cohorts, +1239C carriers displayed a significantly higher risk of T1DM than +1239A homozygotes (combined cohorts: OR=1.63, 95 percent CI: 1.34-1.97). Clinical analysis did not detect any differences between patients carrying or not +1239C in terms of gender distribution and age at T1DM diagnosis. These data suggest that SPP1 variants marked by +1239C are associated with T1DM development in the Italian population. The predisposing effect may depend on its effect on Opn levels.

Transition process of patients with type 1 diabetes (T1DM) from paediatric to the adult health care service: a hospital-based approach.

INTRODUCTION: The outcomes of different types of transitions of young people with chronic diseases have been poorly investigated. OBJECTIVE: To evaluate and compare a structured transition from the paediatric diabetes services (PDS) into the adult diabetic services (ADS) with an unstructured one. DESIGN: We retrospectively investigated 62 adolescents and young adults with type 1 diabetes discharged from the PDS from 1 January 1994 to 31 December 2004. Thirty-two patients (group A) were transferred to the ADS of the same hospital with an unstructured method (letter) and 30 patients after a structured transfer planned with adult physicians (group B). We analysed the date of the first admission in ADS, the glycated haemoglobin (HbA1c), the clinic attendance rate in PDS and in the first year in ADS, and a phone questionnaire on the transition experience. RESULTS: The duration of the transfer was longer in A than in B with a lack of medical assistance during the unstructured transition (P < 0.001). At the first visit in ADS, before any medical intervention, HbA1c was improved in B compared to the last in PDS (P < 0.01), and had a trend in worsening in A. After 1 year in the ADS there was a better clinical attendance, and a lower HbA1c in B than in A (P < 0.05). All the subjects of group B reported a favourable opinion for the structured transition (P < 0.0001). CONCLUSION: The transition process plays an important role in diabetic care and a structured plan is mandatory to avoid to lose the patients and to get worse their health.

Telecare for teenagers with type 1 diabetes: a trial.

AIM: The aim of this paper was to test in teenagers with type 1 diabetes mellitus (T1DM) the Glucobeeb (Gb), a web based tool to support the diabetes care. METHODS: Gb transfers glucometer's data by phone and Internet to the PC of practitioner in files dedicated to each patient; the response returns to patient as 1-min vocal message. From outpatients paediatric clinic 28 teenagers (mean 14.8 years, range 10-20, male 14) with T1DM on multiple daily injections insulin therapy, with glicated haemoglobin (HbA1c) over 7% and >2 years' duration of the disease (9.1 years, range 2-15), were consequently randomized to telecare (glucometer transmission with feedback, group A) or control (standard communication by phone and face-to-face visits, group B). Glycaemia was tested four times per day and data transmitted every 2 weeks; clinician feedback returned within the following week. Two controls were excluded after randomization. Outcomes of 14 patients of A were compared with 12 of B. RESULTS: In intervention group average HbA1c% decreased from baseline at 3 and 6 months in comparison with controls (9.5, 9.0, 9.1, vs 9.1, 9.4, 9.4 respectively). Controls after 6 months were introduced to Gb, and similar trend of HbA1c was observed in the following examinations at 3 and 6 month (9.4, 8.9, 8.7). Then, in both groups HbA1c after 12 months of Gb increased, and after 18 reduced (A: 9.2, and 8.8, B 9.1 and 8.5 respectively). The enhancement of HbA1c from baseline to end was significant (P=0.01). CONCLUSION: The tool improves metabolic control in teenagers with T1DM.

Defective function of the Fas apoptotic pathway in type 1 diabetes mellitus correlates with age at onset.

The Fas death receptor triggers lymphocyte apoptosis through an extrinsic and an intrinsic pathway involving caspase-8 and -9 respectively. Inherited defects of Fas function are displayed by a proportion of patients with Type 1 diabetes mellitus (T1DM) especially those with a second autoimmunity (T1DM-p). This study assesses activation of both pathways in Fas-resistant (FasR) patients to localize the defect. 21/28 (75 percent) T1DM-p, 14/50 (38 percent) T1DM, and 7/150 (5 percent) controls were FasR. Analysis of the 35 FasR patients and 20 Fas-sensitive (FasS) controls showed that caspase-9 activity was lower in T1DM-p and T1DM than in controls, whereas caspase-8 activity was lower in T1DM-p than in T1DM and the controls. Single patient analysis showed that 16/35 patients displayed defective activity of one (FasR1), whereas 19 displayed normal activity of both caspases (FasR2). Ages at onset of diabetes mellitus in T1DM and the second autoimmune disease in T1DM-p were lower in FasR than in FasS patients. All FasR1 patients developed diabetes mellitus before the age of 9 years, whereas a later onset was displayed by 26% FasR2 and 53% FasS patients. These data show that defective Fas function may involve both the extrinsic and intrinsic pathway in T1DM and severity correlates with the precocity of the autoimmune attack and its tissue polyreactivity.

Transient chorea in a patient with type 1 diabetes may induce a reduction in insulin demand through increased spontaneous movements.

The importance of physical activity in the management of diabetes is well established. The effect of programmed exercise and measurable skeletal activities on diabetes has been variously studied. Chorea induces an increase in spontaneous movement. Its occurrence in a teenager with type 1 diabetes provides new insights into our knowledge of metabolic outcomes. In our patient, the reduction in daily insulin demand was linked to choreic movement: a 67% decrease in insulin supply was needed to avoid episodes of hypoglycaemia; moreover, improved metabolism (measured as glycated haemoglobin) was obtained. Since no dietary changes were made and clinical events (including fever, drugs, weight loss, voluntary physical activity, psychological opposition or refusal of treatment) interfering with metabolic control of diabetes occurred, it appeared that only increased physical movements due to chorea reduced the patient's insulin requirement. As spontaneous movements declined with healing, metabolic control was lost, requiring an increase in insulin dosage to restore it. This article sheds additional light on our current understanding of hypoglycaemia and the variability of exogenous insulin demand in childhood and adolescent diabetes, when there are spontaneous movements and play. This finding highlights the importance of movement in type 1 diabetes.

[Urinary tract infections: review of the case records of the 5-year-old population of Novara]. / Le infezioni delle vie urinarie. Revisione della casistica della popolazione novarese di cinque anni.

AIM: A feverish high temperature is the symptom that most frequently leads families to take their children to a Pediatric First Aid unit. In the differential diagnosis of the causes of hyperpyrexia the presence of infections of the genito-urinary tract have to be excluded. Infections of the urinary ways are often the cause of high temperatures in infancy, particularly during the 1st year of life; early identification at the moment of examination at the Paediatric First Aid clinic of patients with infections of the urinary ways makes it possible to prevent the onset of renal complications. We carried out a retrospective study with the purpose of evaluating the incidence of infections of the urinary ways and their complications in paediatric patients who had come to the First Aid unit for hyperpirexia and were later hospitalised after examination of the urine revealed and infection of the urinary ways. METHODS: The study was carried out by consulting the registers listing arrivals at the First Aid unit and the subsequent discharge diagnosis. We then consulted the clinical records of patients who required admission to our Paediatrics Clinic arter the first aid examination. RESULTS: Re-reading the registers of examination carried out and the clinica records of hospitalised patients there emerged an increase in the observation of this pathology, diagnosed at the moment of the First Aid examination by means of rapid tests and thereafter assessed by haematochemical and radiological tests. CONCLUSIONS: In our opinion this increase could be attributed to the greater attention paid to diagnosing the causes of fever of apparently unknown origin.

Younger age at diagnosis of type 1 diabetes mellitus in children of immigrated families born in Italy.

The aim of this study was to evaluate the age of immigrants' children at diagnosis of Type 1 diabetes (T1DM) according to their country of birth. Immigration from developing countries to a westernised area causes rapid changes in the environmental conditions, and we investigated whether the location of birth, either inside or outside Italy, is associated with age at diagnosis of diabetes. Out of a prevalent hospital-based cohort of 5718 T1DM children cared for in 2002 in 47 Italian Pediatric Diabetes Units, we recruited 195 children (M: 97) of immigrants from developing countries--119 were born in Italy and 76 outside the European Union. Children with only one immigrant parent (no. 42) were also included. Age at diagnosis of T1DM, and other variables were compared with those of Italian children. Children of immigrated families born in Italy developed T1DM at a median age of 4.0 yr (IQR 2.2-6.9), whereas those born in developing countries and that had immigrated to Italy after birth developed T1DM at a median age of 7.9 yr (IQR 5.1-10.7, p < 0.001). Among the children born in Italy, 77 had parents who were both immigrants and the children's median age at diagnosis was 3.8 yr (IQR 2.1-6.3); 42 had only one immigrant parent and, when it was the father (no. = 23), median age was even younger (2.9 yr, IQR 2.0-8.2). Ten children had immigrated in their first yr of life and their median age was 9.1 yr (IQR 5.0-10.6). The median age of the Italian children was 6.6 yr (IQR 3.6-9.5). Results show that the outbreak of T1DM is earlier in immigrants' children born in Italy than in original countries.

Evolution of coinfection with human immunodeficiency virus and hepatitis C virus in patients treated with highly active antiretroviral therapy.

A retrospective analysis of data from a cohort of patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were treated with highly active antiretroviral therapy (HAART) at 3 infectious diseases units in northern Italy was performed. While the patients were receiving HAART, CD4(+) cell counts significantly increased and HIV RNA serum levels decreased. However, no significant overall changes in alanine aminotransferase (ALT) levels and HCV RNA serum levels were observed. Fifteen (4.6%) of 323 patients died within 3 years of follow-up; death was related to cirrhosis in 5 patients (1.6%). No significant difference was observed between cirrhosis-related mortality and mortality related to other causes. Patients with ALT levels >4 times the normal values at initiation of HAART showed a significant decrease in ALT levels, whereas patients with normal ALT levels at initiation of HAART showed a significant increase over time, suggesting that HAART may have long-term beneficial or detrimental effects, depending on patient characteristics.

Defective function of Fas in patients with type 1 diabetes associated with other autoimmune diseases.

Fas (CD95) triggers programmed cell death and is involved in cell-mediated cytotoxicity and in shutting off the immune response. Inherited loss-of-function mutations hitting the Fas system cause the autoimmune/lymphoproliferative syndrome (ALPS). We have recently shown that ALPS patients' families display increased frequency of common autoimmune diseases, including type 1 diabetes. This work evaluates Fas function in type 1 diabetic patients without typical ALPS. Cell death induced by anti-Fas monoclonal antibody was investigated in T-cells from 13 patients with type 1 diabetes alone and 19 patients with type 1 diabetes plus other autoimmune diseases (IDDM-P). Moreover, we analyzed 19 patients with thyroiditis alone (TYR), because most IDDM-P patients displayed thyroiditis. Frequency of resistance to Fas-induced cell death was significantly higher in patients with IDDM-P (73%) than in type 1 diabetic (23%) or TYR (16%) patients or in normal control subjects (3%). The defect was specific because resistance to methyl-prednisolone-induced cell death was not significantly increased in any group. Fas was always expressed at normal levels, and no Fas mutations were detected in four Fas-resistant IDDM-P patients. Analysis of the families of two Fas-resistant patients showing that several members were Fas-resistant suggests that the defect has a genetic component. Moreover, somatic fusion of T-cells from Fas-resistant subjects and the Fas-sensitive HUT78 cell line generates Fas-resistant hybrid cells, which suggests that the Fas resistance is due to molecules exerting a dominant-negative effect on a normal Fas system. These data suggest that Fas defects may be a genetic factor involved in the development of polyreactive type 1 diabetes.

Early onset of gastric carcinoma and constitutional deletion of 18p.

We report on the association of a gastric carcinoma and a constitutional deletion of the short arm of chromosome 18 in a 14-year-old patient. The phenotype of the patient, including microcephaly, ptosis, micrognathia, tetralogy of Fallot, and mental retardation, fits well with previously reported cases of del(18p); she also showed a positive serology against Helicobacter pylori. The comparison of the alleles of polymorphic loci located on the short arm of chromosome 18 between the patient and her parents showed a maternal origin of the abnormal chromosome. Loss of heterozygosity (LOH) for loci located in the long arm of chromosome 18 is a frequent event in gastric carcinomas; it was observed in the tumoral mass of our patient and again, the alleles lost were of maternal origin. We postulate that the constitutional chromosomal abnormality may have favored the loss of the abnormal chromosome in some cells and that the loss of the deleted chromosome 18 (demonstrated by LOH for this chromosome in the tumoral mass) has been an early step in the pathogenesis of the gastric carcinoma of our patient with Helicobacter pylori infection acting as a cofactor.

[24 Hour arterial pressure in insulin-dependent diabetics and non-insulin-dependent diabetics with preserved renal function]. / Pressione arteriosa/24 h in diabetici insulino-dipendenti e non insulino-dipendenti con conservata funzione renale.

BACKGROUND: The aim of the study was to value the behaviour of systolic (S) and diastolic (D) arterial pressure (AP)/24 hrs in a group of diabetic patients insulin-dependent (IDDM) and non insulin-dependent (NIDDM) with preserved renal function. METHODS: We examined 65 diabetic patients (aged 39.1 +/- 23.3), 33 IDDM (aged 18.2 +/- 7.5; years of diabetes: 5.8 +/- 4.9) and 32 NIDDM (aged 60.7 +/- 11.4; years of diabetes: 7.2 +/- 7.5). In all of them we computed BMI and determined creatinine clearance, glycosylated haemoglobin A, total and HDL-associated cholesterol, triglyceridemia, middle glycemia and microalbuminuria. AP measurement was performed by 24 hrs monitoring (periodicity 15') using a Takeda 2420 measurer. Chronobiological characteristics of AP were analysed by statistical method of cosinor according to Halberg, examining if there was or not a blood pressure circadian rhythm (PCR) (p < 0.05) and its characteristics represented by the mesor, the amplitude and the acrophase. Moreover the patients were subjected to a diet with fixed contents of sodium (130 mEq/day) and afterwards we drew (every 4 hours) renin (R), aldosterone (A1) and atrial natriuretic factor (ANF) which were analysed with cosinor's method. The purpose was not to compare the two populations, not homogeneous between them and not different only for the years of diabetes, but to study their blood pressure behaviour, the rhythm, the order of the indicated hormones for possible pathogenetic connections. RESULTS: NIDDM presented higher blood pressure values (PAS 134.2 +/- 3.5 and PAD 80.9 +/- 2 mmHg) than IDDM (PAS 116.6 +/- 1 and PAD 66.4 +/- 1.7 mmHg), still in limits of substantial normality. The acrophase was in the midday for NIDDM (PAS 11:25', PAD 12:06') and in the early afternoon for IDDM (PAS 14:15', PAD 14:06'). Analysing the trend of the AP in the single cases, PCR was present in 70% and absent in 30% of IDDM while it was persistent in 56% and disappeared in 44% of NIDDM. IDDM without PCR differed from those with it in years of diabetes (p < 0.001), body weight (p < 0.02), BMI (p < 0.01), triglyceridemia (p < 0.05), all more elevated, as well as in higher PAS and PAD (p < 0.001) and in higher concentration of ANF (p < 0.05). The same comparison was done in NIDDM. Patients without PCR were older (p < 0.025), had higher PAS (p < 0.025) and PAD (p < 0.001) and also a more activated ANF (p < 0.001). CONCLUSIONS: This hormonal anomaly may be ascribed to a lower excretion of sodium with consequent expansion of extracellular volume due to antinatriuretic action of insulin often found at high plasmatic levels particularly in NIDDM.

[Sepsis caused by Haemophilus influenzae type B with septic arthritis in an infant]. / Sepsi da Haemophilus influenzae tipo b con artrite settica in un lattante.

Septic arthritis is a serious pyogenic infection that may lead to permanent orthopedic sequelae. Infants represent the most of the cases. It usually develops as a result of bacterial seeding into the capillary-rich synovium in the course of a bacteremic episode. Etiology changes according to different ages; in children after the neonatal period but younger than 24 months, Haemophilus influenzae is the most frequent causative organism. A case of sepsis due to Haemophilus influenzae type b (Hib) with septic arthritis in a patient 3 months old, is reported. The child was admitted to the hospital with a very high temperature (39 degrees C) for five days. His right wrist and ankle appeared swelling and hyperemic. He was affected by congenital cardiopathy from birth. He was not immunizated against Hib. The blood colture was positive for Hib. The leukocyte count was 21,400 cell/mm3 with 55% of polymorphonuclear cells. During the second day of recovery, the patient was transfused, because of the very low value of hemoglobin (5.2 g/dl). The child was treated with netilmycina and ceftriaxone for 15 days. The temperature fell in two days. The articular pathology resolved in nearly ten days. The case reported confirms the importance of septic arthritis as a pathology that necessarily requires an early diagnosis and treatment. The Haemophilus influenzae vaccine, is recommended especially in immunocompromised or cardiopathic subjects and before the age of 2 years.

Osteosintesis intramedular de la tibia a cielo cerrado / Closed intramedullary osteosyntesis of the tibia

Hey Groves, en 1918, fue el primero en introducir la fijacion intramedular para la fracturas de la diafisis femoral que, en 1940, fue popularizada por Kunstcher, por el metodo cerrado. Operamos 17 casos, en el hospital de la Caja Nacional de la Ciudad de Santa Cruz, con fractura de la diafisis tibial, fijado intramedularmente con clavos de Kunstcher a cielo cerrado, con uso de intensificador de imagenes. Detalles y resultados de la tecnica quirurgica fueron descritos con el uso de una incision minima sobre el tendon rotuliano , para facilitar morbilidad como fue descrito anteriormente por otros autores. La experiencia nos permite concluir, que esta tecnica es segura, con excelentes resultados y pocas complicaciones.

[Herpetic encephalitis with biphasic course. A case report and review of the literature]. / Encefalite erpetica a decorso bifasico. Descrizione di un caso e revisione della letteratura.

Encephalitis represents an important event in pediatric practice. Between the different causes Herpes Simplex Virus (HSV) seems to be the most significant etiological agent, not only for its frequency but chiefly for conditioning prognosis. The Authors report a new case of HSV encephalitis with biphasic course illustrating the most recent pathologic, diagnostic and therapeutic features in the attempt to individualize those factors, between clinical data, laboratory findings and imaging that allow early diagnosis and consequently precocious specific antiviral therapy.