Concetta Sferlazzas

Bone demineralization in cystic fibrosis : Evidence of imbalance between bone formation and degradation

Bone turnover, collagen metabolism, and bone mineral status were investigated in 59 patients with cystic fibrosis and in 72 sex- and age-matched control subjects. In all patients and control subjects serum concentrations of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen(PIIINP), and cross-linked carboxy-terminal telopeptide of type I collagen(ICTP), and urinary values of cross-linked N-telopeptides of type I collagen (NTX), as well as total body bone mineral content (TBBM) were measured. Higher ICTP (μg/L) and NTX (bone collagen equivalent/urinary creatinine (nmol/mmol) values were found in prepubertal, pubertal, and young adult patients than in control subjects (ICTP: 15.4 ± 2.1 and 13.2± 1.8, p < 0.001; 23.3 ± 5.3 and 20.1 ± 4.1,p < 0.02; 4.8 ± 1.1 and 4.0 ± 1.0, p < 0.05, respectively; NTX: 1047.5 ± 528.6 and 227.8 ± 71.8,p < 0.01; 997.8 ± 391.7 and 376.3 ± 91.0,p < 0.01; 993.2 ± 398.0 and 73.9 ± 28.5,p < 0.01, respectively). Lower OC and PICP levels (μg/L) were showed in pubertal patients in comparison with control subjects (OC: 20.2± 12.3 and 39.0 ± 15.1, p < 0.01; PICP: 305.8± 130.4 and 436.2 ± 110.1, p < 0.02, respectively). Lower OC and higher PIIINP levels (μg/L) were found in young adult patients than in control subjects (OC: 4.4 ± 3.0 and 7.0 ± 3.1,p < 0.05; PIIINP: 4.8 ± 1.1 and 3.1 ± 1.0,p < 0.001, respectively). TBBM (z score) was reduced in prepubertal, pubertal, and young adult patients (-0.8 ± 0.4, -1.0± 0.4, -1.1 ± 0.5, respectively). Patients with cystic fibrosis have bone demineralization and imbalance between bone formation and degradation.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Background: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. Methods: In 1996 an IBD register of disease onset was established on a national scale. Results: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohns disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996–2003 an increase of IBD incidence from 0.89 to 1.39/105 inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. Conclusions The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Factors affecting diabetes mellitus onset in cystic fibrosis: evidence from a 10-year follow-up study.

This study reports the results of genotype characterization and of a 10‐y prospective evaluation of clinical status, glucose tolerance and insulin secretion in 28 originally normoglycaemic patients with cystic fibrosis (CF). The aim of the study was to assess whether any genetic, clinical or metabolic parameters could identify in advance those patients at risk of developing diabetes mellitus over time. During the follow‐up 42.8% of patients became diabetic. Neither gender, age nor clinical parameters were significantly different at entry in the patients who eventually developed diabetes compared with those who did not. Insulin secretion during oral glucose tolerance tests (OGTT) deteriorated over time in both groups, whereas a progressive deterioration of glucose tolerance was only evident in the patients who developed diabetes and increased baseline glucose areas were the only predictive parameter of diabetes onset. Genotype analysis revealed significant differences between patients with and without diabetes: ΔF508 homozygosis was more frequent in the first group and N1303K mutation in the second group. In conclusion, in CF: (i) increased glucose areas during OGTT and deterioration of glucose tolerance over time can predict the evolution towards diabetes; and (ii) ΔF508 homozygosis may predispose to the risk of diabetes, whilst N1303K mutation seems to play a protective role.

Is intestinal biopsy always needed for diagnosis of celiac disease

OBJECTIVE:Intestinal biopsy is required for a diagnosis of celiac disease (CD). The aim of this study was to assess diagnostic accuracy of transglutaminase antibodies (TGA) in comparison and in association with that of antiemdomysial antibodies (AEA), calculating the post-test odds of having the disease, to verify whether some patients might avoid undergoing intestinal biopsy for a diagnosis of CD.METHODS:A total of 181 consecutive patients (131 < 18 yr), referred to our celiac clinic by primary care physicians for suspect CD. Overall diagnostic accuracy, negative predictive value, and likelihood ratio (LR) were calculated both for each serological test and for serial testing (TGA and after AEA, assuming the post-test probability of TGA as pretest probability of AEA). Both serological determination and histological evaluation were blindly performed. Histology of duodenal mucosa was considered the gold standard.RESULTS:The overall accuracy of TGA and of AEA were 92.8% (89.1–96.6) and 93.4% (89.7–97.0), respectively. The negative predictive value of TGA and AEA were 97.2% (91.9–102.6) and 87.2% (77.7–96.8), respectively. Positive likelihood ratios for TGA and AEA were 3.89 (3.40–4.38) and 7.48 (6.73–8.23), respectively. Serial testing, in groups of patients with prevalence of CD estimated higher than 75%, such as those with classic symptoms of CD, would provide a post-test probability of more than 99%.CONCLUSIONS:Our results suggest that serial testing with TGA and AEA might allow, in some cases, the avoidance of intestinal biopsy to confirm the diagnosis of CD.

Chronic urticaria and associated coeliac disease in children: A case–control study

Celiac disease (CD) and chronic urticaria (CU) are both sustained by immune mechanisms, but there are so far few data on their clinical association. We performed a case–control study to determine the occurrence of CD in urticaria and matched control children, and to assess the clinical relevance of this association. Children and adolescents were diagnosed to have severe chronic idiopathic urticaria in the presence of hives for more than 6 wk poorly or not responsive to oral antihistamines. Other known causes of urticaria had to be excluded. A matched control group without urticaria was enrolled. In both groups, the presence of CD was searched by assaying antitransglutaminase and antiedomysial antibodies, and confirmed with endoscopic intestinal biopsy. Results. CD was diagnosed and confirmed in 4/79 (5.0%) of children with CU and in 17/2545 (0.67%) of the controls (p = 0.0003). In the four children with urticaria and CD the gluten free diet (GFD) lead to complete remission of urticaria within 5–10 wk, whereas the disappearance of serological markers occurred in longer times (5–9 months). Conclusions. The presence of CD in children with CU was significantly more frequent than in controls. GFD resulted in urticaria remission. CD may be regarded in such subjects as a cause of CU.

Increased Frequency of the Immunoglobulin Enhancer HS1,2 Allele 2 in Coeliac Disease

Background: Coeliac disease (CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3′ of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3′ to C alpha-1 in CD patients compared to a control population was analysed. Methods: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR). Results: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio (OR) showed that those with 2/2 and 2/4 (OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD (OR 0.52, P = 0.01). Conclusions: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis.

Reliability and usefulness of random fecal α1-antitrypsin concentration: further simplification of the method

The reliability of random fecal alpha 1-antitrypsin (FA-1-AT) concentration has been evaluated by comparing FA-1-AT values on random specimens and on concomitant 24-72 h fecal collections. In order to simplify the method, FA-1-AT data derived from lyophilized fecal samples were compared with those obtained from 37 degrees C heat-dried fecal samples. Random FA-1-AT concentration was assayed in 80 children with various gastrointestinal illnesses and 36 healthy age-matched controls. There was a close relationship between FA-1-AT values obtained from random samples and 1-day or 3-day collections. There was also a significant relationship between FA-1-AT values derived from the two different ways of drying the stools. Mean FA-1-AT values were statistically different when compared to the controls in the following groups of disorders: untreated and after-gluten-challenge celiac disease, post-enteritis syndrome, and cows milk intolerance. The possible meanings of the abnormal FA-1-AT concentration in the various disorders are discussed. We conclude that FA-1-AT is a simple and reliable test for enteric protein loss. The simplification of the method proposed by us should reduce the cost of the test and moreover make it feasible in all laboratories.

Thyroid function in children with cystic fibrosis

Serum concentrations of T4, T3, reverse T3 (rT3), TSH, Thyroxine binding globulin (TBG) and Thyroxine binding prealbumin (TBPA) were measured and a TRH-stimulation test was performed in 10 iodide untreated children affected by cystic fibrosis (CF) and in 84 controls.As compared to the controls, CF patients had lower T4 and rT3, similar T3 and TBG and increased T3:T4 ratios. They also had lower TBPA, but this could not account for the low T4. Finally they had higher basal and TRH-stimulated TSH. Our results indicate subclinical hypothyroidism in CF. The mechanisms responsible for this situation are not elucidated by our data.

Effects of a gluten-free diet on catch-up growth and height prognosis in coeliac children with growth retardation recognized after the age of 5 years

The effects of a gluten-free diet on catch-up growth and predicted height were evaluated in 12 children with coeliac disease diagnosed after the age of 5 years and followed for 2–5.5 years. In the majority of the patients, height and bone age were retarded at the time of diagnosis. Under a gluten-free diet growth velocity, age-related height, predicted height and relative bone age increased, height for bone age slightly decreased. In four patients the predicted height remained below the target height, indicating incomplete catch-up growth.

Redefining the intraepithelial lymphocytes threshold to diagnose gluten sensitivity in patients with architecturally normal duodenal histology

Aliment Pharmacol Ther 2011; 33: 697–706