Permanent diabetes mellitus in the first year of life

AIMS/HYPOTHESIS: The pathogenesis of permanent diabetes mellitus diagnosed early in life is heterogeneous and, in most cases, not known. We aimed at identifying markers differentiating between non-autoimmune and autoimmune diabetes. METHODS: The clinical, genetic and epidemiological features of 111 diabetic patients (62 males) who received insulin within 12 months of life were studied. RESULTS: The epidemic curve by age of diabetes onset revealed two subsets of patients at a cutoff of 180 days. In the group with diabetes onset before 180 days ("early onset" permanent diabetes) the analysis of HLA susceptibility heterodimers (available for 21 individuals) showed that 76% had a "protective" HLA genotype for Type I (insulin-dependent) diabetes mellitus as compared to 11.9% (5/42) of the later onset group. Accordingly, "early onset" children were less likely to have autoimmunity markers (4 out of 26 tested) than children with onset after 180 days (13 out 20 tested) (15.4% vs. 65.0%, p<0.01). Of note, 19 out of 20 (or the 95%) patients who were born on the island of Sardinia, an Italian region where the incidence of Type I diabetes is six times higher than continental Italy (33/100,000/year vs 5/100,000/year), were included in the later onset group (>180 days). Small-for-date birthweight, a possible sign of reduced foetal insulin secretion, was more common in the "early onset" group (OR=9.9, 95%-CI 2.6-38.6). CONCLUSION/INTERPRETATION: These results, obtained in the largest population-based cohort of diabetic infants hitherto reported, suggest that "early onset" permanent diabetes cases differ from later onset cases and that most of them do not have an autoimmune pathogenesis.     

Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm‐aging”

Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as “damage‐associated molecular pattern” (DAMP) agents and cause inflammation. As many elderly people are characterized by a low‐grade, chronic inflammatory status defined “inflamm‐aging,” we evaluated if circulating mtDNA can contribute to this phenomenon. Eight hundred and thirty‐one Caucasian subjects were enrolled in the study, including 429 siblings aged 90–104 (90+ siblings). mtDNA plasma levels increased gradually after the fifth decade of life. In 90+ subjects, mtDNA values of two members of the same sibling relationship were directly correlated, suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA. The subjects with the highest mtDNA plasma levels had the highest amounts of TNF‐α, IL‐6, RANTES, and IL‐1ra; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines. In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo resulted in an increased production of TNF‐α, suggesting that mtDNA can modulate the production of proinflammatory cytokines. Our findings therefore show that circulating mtDNA increases with age, and can significantly contribute to the maintenance of the low‐grade, chronic inflammation observed in elderly people.     

Acute promyelocytic leukaemia: epidemiology and risk factors. A report of the GIMEMA Italian archive of adult acute leukaemia

Abstract: Acute promyelocytic leukaemia (APL) exhibits peculiar epidemiological, clinical, cytogenetic and molecular features, compared to the other acute myeloid leukaemias (AML). Data on epidemiology and occupational risk factors for APL desumed from the GIMEMA archive are reported and compared with those of the other AML. An exploratory case-case study was designed on AML patients from 56 haematology centres in Italy. Overall, 4296 patients older than 15 yr with a new diagnosis of acute leukaemia were recorded between July 1992 and July 1997. Of these, 335 were classified as APL, and 2894 as other AML. The median age of APL patients was 43 compared to 59 yr for the other AML (p< 0.00001). In order to identify peculiar risk factors for APL development, different parameters were compared in the 2 groups. After adjusting by age no significant differences were observed with regard to education, lifetime prevalence of cancer among siblings and previous diseases in the patient's history. Occupational exposure as a possible risk factor for APL showed no increased risk compared to other AML among farmers, builders and leather workers. A significant association was found in electricians (OR = 4.4, 95% CI = 2.0–9.7) and a weak association was found in wood workers (OR = 3.2, 95% CI = 0.8–10.8). The proportion of APL with respect to other AML was significantly higher in the north east of Italy compared to the rest of the country (OR = 1.7, 95% CI = 1.3–2.2). These data confirm the younger age of APL patients compared to the other AML. A possible role of electromagnetic fields is suggested by the higher risk of APL in electrical workers and in the more industrialized areas of the country.     

Concentration of elements in serum of patients affected by multiple sclerosis with first demyelinating episode: a six-month longitudinal follow-up study

Twenty-six chemical elements and oxidative status were determined in serum of 12 patients with first demyelinating episode and brain magnetic resonance imaging compatible with the disease at different time points. Quantifications of Al, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Hg, Li, Mg, Mn, Mo, Ni, Pb, Sb, Si, Sn, Sr, V, Tl, W, Zn and Zr, as well as of serum oxidative status and antioxidant capacity were carried out. The results were compared with values obtained from healthy subjects living in the same geographic area. Concentration variability, expressed as coefficient of variation (CV), was evaluated over a six months longitudinal follow-up. The CV was higher for Li and Pb, while showed minimal variation for Ca, Cu, Mg and Zn--elements strictly body regulated. Significant difference (p < or = 0.05) in mean concentrations of Ba, Ca, Cd, Cr, Li, Mn, Mo, Ni, Sb, Si, Sn and Zr between patients at time 0 and controls was also found.     

Increasing hepatitis B vaccination coverage among healthcare workers in Italy 10 years apart

BACKGROUND: In Italy, vaccination against hepatitis B virus infection was strongly recommended for healthcare workers since 1985. Update findings on vaccination coverage are lacking. AIM: To assess current vaccination coverage against hepatitis B in this job category. METHODS: In 2006, 1,632 healthcare workers randomly selected in 15 Italian public hospitals completed a self-administered precoded questionnaire. RESULTS: The overall vaccination coverage was 85.3%, a figure higher than the 64.5% observed in 1996. Vaccine coverage showed a significant downtrend (p<0.01) from the Northern (93.1%) to the Southern (77.7%) areas. Logistic regression analysis showed that residence in the North (Odds ratio 4.2; 95% confidence interval 2.6-6.7) and youngest age (Odds ratio 4.5; 95% confidence interval 2.6-7.8), both were independent predictors of vaccine acceptance. CONCLUSIONS: Ten years apart, vaccine coverage has markedly increased, closely paralleling the downtrend in the incidence of acute B hepatitis among healthcare workers in Italy.     

The first large population based twin study of coeliac disease

BACKGROUND AND AIMS: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. METHODS: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. RESULTS: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1-134), independent of the DQ at risk genotype. CONCLUSION: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.     

High prevalence of hepatitis B virus infection in B-cell non-Hodgkin's lymphoma

In this hospital-based, multicenter case-control study we investigated the prevalence of hepatitis B virus (HBV)-related markers and HBV/hepatitis C virus (HCV) co-infection among B-cell non-Hodgkin's lymphoma (B-NHL) cases and controls. Four hundred newly diagnosed B-NHL cases and 392 controls from other departments of the same hospitals were studied. The prevalence of positivity for hepatitis B surface antigen (HBsAg) was 8.5% among B-NHL cases and 2.8% among controls (adjusted odds ratio, 3.67; 95% confidence interval, 1.75-7.66). HBV/HCV co-infection was found in four cases, but in no controls. The finding of a positive association between HBV infection and B-NHL raises the possibility that HBV may play an etiologic role in the induction of B-NHL.     

Serum transforming growth factor ��1 during diabetes development in non-obese diabetic mice and humans

Recent data show that regulatory cells with transforming growth factor (TGF)‐β1‐dependent activity are able to restore self‐tolerance in overtly diabetic non‐obese diabetic (NOD) mice. Thus, TGF‐β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF‐β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet‐related antibody. Serum TGF‐β1 (both total and active) was measured by enzyme‐linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow‐up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF‐β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF‐β1 (aTGF‐β1) serum levels. In mice, aTGF‐β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin‐positive cells. Our findings suggest that in NOD mice serum TGF‐β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF‐β1 in islet‐related antibody‐positive subjects may provide insights into the natural history of prediabetic phase of T1D.     

Concordance, disease progression, and heritability of coeliac disease in Italian twins

BACKGROUND AND AIMS: We adopted the twin method to disentangle the genetic and environmental components of susceptibility to coeliac disease (CD). We estimated disease concordance rate by zygosity and HLA genotypes, discordance times, progression rates to disease, and heritability. METHODS: We crosslinked the Italian Twin Registry with the membership lists of the Italian Coeliac Disease Association and recruited 23 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs with at least one affected member. Zygosity was assigned by DNA fingerprinting, and HLA-DQ and DR alleles were genotyped. Disease status was ascertained by antiendomysial, anti-human tissue transglutaminase antibodies, and bowel biopsy. RESULTS: Concordance was significantly higher in MZ (83.3% probandwise, 71.4% pairwise) than in DZ (16.7% probandwise, 9.1% pairwise) pairs. Concordance was not affected by sex or HLA genotype of the co-twin and being MZ was significantly associated with the occurrence of CD (Cox adjusted hazard ratio 14.3 (95% confidence interval 4.0-50.3)). In 90% of concordant pairs the discordance time was 相似文献