Current Espghan Guidelines for Celiac Disease in Pediatric Age, Tertiary Care Center Experience: A Proposal for Further Simplification.

According to the 2012 ESPGHAN criteria for diagnosis of celiac disease (CD), duodenal biopsy (DB) can be avoided in children with a clear malabsorption syndrome, anti-tissue transglutaminase IgA (tTG2) ≥ 10x the cut-off, anti-endomysium IgA (EMA) and HLA DQ2/DQ8 genes. The aim of this study is to report our experience and evaluate the accuracy of the actual guidelines. PATIENTS AND METHODS: This is a retrospective study conducted on all patients diagnosed CD from 2012 to 2018 in our Center. For all patients enrolled were analyzed: data of family history, symptoms, serology, genetics, Marsh grade and follow-up. RESULTS: A total of 481 children [mean age 6,4 yrs; F:M= 1.8:1] were included in the study. The mean age of patients who were not subject to DB was lower (4.51 yrs) comparing with patients that received DB (6.48 yrs). Out of the 256 patients with anti-tTG2 ≥ 10 fold, 121 underwent DB because of mild symptoms (84/121) or no symptoms (37/121). In all cases Marsh type 3 was found and HLA haplotypes was compatible with CD diagnosis. CONCLUSIONS: Our study confirms that the serology has a primary importance to diagnose CD, regardless of the symptoms. These data suggest that biopsy and HLA haplotypes search, in presence of anti-tTG2 IgA ≥ 10x the cut-off, are wasteful and unhelpful for the patients.

Electric field controlled columnar and planar patterning of cholesteric colloids.

We study how dispersions of colloidal particles in a cholesteric liquid crystal behave under a time-dependent electric field. By controlling the amplitude and shape of the applied field wave, we show that the system can be reproducibly driven out of equilibrium through different kinetic pathways and navigated through a glassylike free energy landscape encompassing many competing metastable equilibria. Such states range from simple Saturn rings to complex structures featuring amorphous defect networks, or stacks of disclination loops. A nonequilibrium electric field can also trigger the alignment of particles into columnar arrays, through defect-mediated force impulses, or their repositioning within a plane. Our results are promising in terms of providing new avenues towards controlled patterning and self-assembly of soft colloid-liquid crystal composite materials.

[Collaborative study on peritoneal dialysis (PD) as first dialysis treatment in an Italian region: 1994-2000]. / Studio collaborativo sulla dialisi peritoneale (DP) come primo trattamento nel Lazio: 1994-2000.

BACKGROUND: In Lazio, only about 5% of uremic patients are on peritoneal dialysis (PD). The present study focuses on the parameters of PD selection, the treatment schedules, and the clinical outcomes of PD patients in the nine public facilities offering a PD program. A cohort of 249 first-time PD patients, from July 1, 1994 to December 31, 2000, was retrospectively considered. METHODS: For the enrollment of the patients, the Regional Dialysis Registry databank was consulted. On December 31, 2000, a systematic review of patient charts was performed to extract the reasons for the PD choice, details of PD schedule, peritonitis episodes, reasons for drop-out, and patient survival rates. In regard to technique success-defined as the probability of having a patient alive on PD-change of modality and death were considered as final events. In regard to patient survival, only death, even in the first 2 months after a shift to hemodialysis, was considered the end point. RESULT: The main PD selection reasons were patient and/or nephrologist preference in 90% of cases. One-hundred eighty-nine patients (76%) had been started on CAPD. During the follow-up, 38.2% dialysis schedules had been modified at least once. At the end of follow-up, 41.2% patients were on APD. The peritonitis rate was one episode per 30 patient-months (1 per 27 patient-months in CAPD; 1 per 37 patient-months in APD; p = 0.08). The technique success rate was 66.3% after 2 years and 49.8% after 3 years. The patient survival rate was 81.1% after 2 years and 68.7% after 3 years. CONCLUSIONS: Patients chose PD as a first dialysis treatment mainly because of reasons unrelated to their clinical status. The technique's success, patient mortality rates, and the peritonitis rate do not explain the low PD diffusion in the region. The peritonitis rate meets the target criteria for excellence recommended by the Italian Society of Nephrology. The observed outcomes may have been favored by the selection of motivated patients and by the increased use of APD.

Omeprazole-induced acute interstitial nephritis.

Omeprazole is a proton pump inhibitor widely used for the treatment of peptic ulcer disease. We report a patient presenting nonoliguric acute renal failure following omeprazole treatment. Both eosinophilia and eosinophiluria were observed, and the patient was diagnosed as having drug-induced acute interstitial nephritis. Renal failure spontaneously resolved when omeprazole was discontinued.

Hypergastrinemia in rats with azoxymethane-induced colon cancers.

Gastrin has been suggested to be involved in the promotion and progression of colon cancer. Mice colon cancers and colon-carcinoma cell lines are stimulated to grow by gastrin, and gastrin receptors have been found in the majority of human colon-tumor specimens. High serum gastrin levels have been reported in patients with colon polyps and cancers, together with increased ornithine decarboxylase (ODC) activity. Since gastrin stimulates ornithine decarboxylase in colon cancer cells in vitro it has been suggested that increased synthesis of intracellular polyamines is one of the mechanisms activated by the hormone. In order to confirm the presence of hypergastrinemia in colon cancer and to investigate the relationship between plasma gastrin and tumor growth, we used an animal model of colon carcinogenesis that minimizes the possible bias of human studies, related to varying diet, age and environmental factors. We evaluated blood gastrin levels in 35 rats with colon cancer induced by the carcinogen azoxymethane (AOM), and we correlated gastrinemia with tumor proliferation, assessed by thymidine-labeling index (TLI) and ODC activity; 6 animals constituted the control group. Gastrin levels in rats with AOM-induced tumors were significantly higher than in controls. Significantly higher TLI and ODC activity were found in the tumors of hypergastrinemic rats than in neoplasms of animals with normal gastrin levels. Our data provide additional evidence of a role for gastrin as trophic hormone for colon neoplastic cells.

Cell kinetics and polyamine enzymes in the intestinal mucosa of rats with azoxymethane induced tumours.

We studied the proliferative activity and the modifications in ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, in the apparently normal intestinal mucosae of rats with azoxymethane induced tumours. Fifty rats were treated with six weekly injections of 15 mg/kg body weight azoxymethane (AOM). Six rats died during the treatment. All the surviving rats developed intestinal tumours; tumour incidence was 93.1% (41/44) in the left colon, 40.9% (18/44) in the right colon and 45.4% (20/44) in the small bowel. In the normal-appearing mucosa close to intestinal tumours we found an extension of the normal proliferative compartment to the upper third of the crypts (stage I abnormality) and a shift of most of the DNA synthesizing cells from the basal region to the middle and upper third (stage II abnormality). Furthermore, the intestinal mucosa characterized by proliferative abnormalities showed an ODC activity significantly higher than the normal mucosa of control rats (small bowel: 1.01 +/- 0.26 vs 0.42 +/- 0.15, P < 0.01; right colon: 1.32 +/- 0.34 vs 0.25 +/- 0.02, P < 0.001; left colon: 1.93 +/- 0.35 vs 0.22 +/- 0.01, P < 0.01). We also detected a significant decrease of DAO activity in the mucosa of the small bowel and right colon of treated rats compared to controls (0.86 +/- 0.09 vs 4.39 +/- 0.85, P < 0.01; 1.04 +/- 0.43 vs 3.80 +/- 0.91, P < 0.01, respectively), while DAO activity in the left colon was unchanged. The lower incidence of tumours in the small bowel and right colon suggests the presence of factors protecting these segments from carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

[The attitude and vaccination practice of a sample of Campania pediatricians]. / Orientamento e pratica vaccinale di un campione di pediatri campani.

One hundred-twenty-six pediatricians were questioned about their attitudes concerning the practice of immunization, their feelings about the new vaccines (measles, mumps, german measles, hepatitis b) and about the pertussis vaccine. 80% of them reported that indications and contraindications were still unclear: Down's syndrome and atopic eczema are still thought to be real contraindications--despite the mass of papers suggesting that they are not so--, moreover 95% of the participants persists into the unnecessary evaluation of the antibody title following hepatitis b immunization. We conclude that it would be wise to periodically diffuse to pediatricians update recommendations about the extended immunization program, especially in our region, were still an high number of children are not properly immunized.

[Nutritional status of CAPD patients in Lazio]. / Stato nutrizionale dei pazienti in CAPD nel Lazio.

Uremic patients have been shown to be frequently malnourished. The amount of glucose absorbed from dialysis solution makes caloric malnutrition unusual among CAPD (Continuous Ambulatory Peritoneal Dialysis) patients. Protein malnutrition is more likely because of loss of nutrients into the dialysate and inhibition of appetite. Present study evaluates nutritional status of 29 patients (20 F, 9 M), 60.31 +/- 16.04, on CAPD since 15.2 months (4-50). Dialysis was scored adequate in all patients, based on the Clinical Assessment Score proposed by the Columbia University Group. Nutritional status was evaluated with (1) Marckmann score, based on relative body weight (RBW), triceps skin fold (TSF), midarm muscular circumference (MAMC), S-transferrin, and (2) Subjective Global Assessment (SGA) based on history, physical examination, anthropometric (BW, skin folds, % body fat according to Durnin, MAMC) and laboratory data (S-albumin, C3, S-transferrin, Hb, lymphocyte count, creatinine appearance rate [CAR], urea nitrogen appearance normalized by BW [NUNA], protein catabolic rate [pcr]). RBW was 118.2% because of excess stored fat; % body fat was > 40% in 6 females and 34.4 +/- 5 in 14 females. Lymphocytes, total proteins, S-albumin, S-transferrin, C3, IgG were normal. CAR (12.2 +/- 3.2 mg/kg/die) and NUNA (101.1 +/- 37.3 mg/kg/die) were lower than normal, as reported for dialysis patients. Marckmann score (26 patients) defined 10 cases of slight malnutrition; SGA (29 patients) identified 2 severely and 14 slightly malnourished patients. Marckmann and SGA scoring however agreed only in 13 over 26 patients. Slight or severe malnutrition has been assessed in CAPD patients in spite of clinically adequate dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Postheparin plasma diamine oxidase values in the follow up of patients with small bowel Crohn's disease.

Measurement of postheparin plasma diamine oxidase (PHD) activity has been proposed to assess mucosal integrity in several diseases of the small intestine. In Crohn's disease, PHD values identify a group of patients with predominantly small bowel mucosal damage. To determine the role of mucosal involvement in the progression of small bowel Crohn's disease and whether different PHD values can predict different outcomes the changes in PHD values in 41 patients with small bowel Crohn's disease admitted consecutively to our department were investigated. The test was performed during periods of active disease and after either medical or surgical treatment had resulted in improvement. PHD values were significantly lower than in normal subjects (normal range 3.7-7.7 U/ml). In 35 patients with active disease (Crohn's disease activity index (CDAI) greater than 150) two groups were identified by choosing a cut off value of 2 U/ml: 93% of the 15 patients with PHD values lower than 2 U/ml (mean (SD) 1.36 (0.46) U/ml) relapsed at least once in the following year, while only the 20% of the 20 whose values were higher than 2 U/ml (mean (SD) 3.69 (1.50)) relapsed in the same period. The data were statistically significant (Yates's corrected chi 2 = 15.63; p less than 0.0001). The positive and negative predictive values of the test were 93% and 80%, respectively. During relapses, PHD values were consistently lower than previous values, and increased significantly after effective medical or surgical treatment. In the six patients in whom there were no changes in disease activity (CDAI persistently less than 150), there was no change in PHD values. This test may be useful for identifying Crohn's disease patients who are likely to relapse. Furthermore, the data indicate that mucosal damage is common in active small bowel Crohn's disease and improves at least in part after treatment.

Intestinal permeability after single dose gluten challenge in coeliac disease.

The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood.

Indications and adequacy of automated peritoneal dialysis in 74 patients.

Experience with chronic intermittent peritoneal dialysis is reviewed to focus on automated peritoneal dialysis (APD) regimens, adequacy and indications. From 1969 to 1990, 74 ESRD patients were treated: 59 patients with Intermittent Peritoneal Dialysis (IPD: 30-40 l x 3/week) and fifteen patients with hour Daily Peritoneal Dialysis (DPD: 25 l x 6 nights/week). Fourty-four patients were regularly treated with IPD. Of these 33 were adequately dialysed, maintaining residual renal function, whilst oligo-anuric patients developed underdialysis. DPD patients were adequately dialysed, having satisfactory peritoneal clearances. Peritonitis rate was 1/19.2 pt months in IPD patients and 1/13.4 pt months in DPD patients. Technique survival was 78% at the end of the first year, and 52% the second year. IPD is adequate only for low body weight patients with residual renal function. In-hospital IPD must be taken into account only for patients unable to perform dialysis without partner assistance. Home DPD, like CCPD and NPD, is generally adequate and yields fairly good quality of life, but the cost is high, probably because of limited ADP diffusion. Prescription must be therefore restricted to patients unable to perform dialysis with working partners, workers who cannot cope with CAPD exchanges, and CAPD failures.

Plasma postheparin diamine oxidase in patients with small intestinal lymphoma.

Diamine oxidase (DAO) is an enzyme located almost exclusively in villus tip enterocytes. Its plasma activity is enhanced by intravenous heparin which releases the enzymes from small bowel enterocytes into the blood. Plasma postheparin DAO (PHD) values have been shown to be significantly lower in patients with malabsorption and villous atrophy, thus suggesting that PHD reflects the mature enterocytic mass. In this study we have assayed PHD in five patients with small bowel lymphoma (two with immunoproliferative small intestinal disease [IPSID] and three with non-IPSID lymphoma) associated with malabsorption syndrome and small bowel mucosa atrophy. The PHD test was performed at diagnosis, after partial or complete remission induced by chemotherapy, and during the follow-up. The PHD values, very low at diagnosis (0.66 +/- 0.12 U/ml), increased during chemotherapy and reached the normal range (greater than 3.7 U/ml) when complete remission occurred. The PHD values rapidly and consistently decreased whenever the disease relapsed. Our data indicate that in patients with small bowel lymphoma PHD test is a sensitive marker of small bowel mucosa damage and suggest that it could be useful in monitoring the recovery of mucosal lesions induced by chemotherapy.

Atopy and coeliac disease: bias or true relation?

Several reports have suggested a relationship between atopy and coeliac disease and atopy has also been linked to the pathogenesis of the mucosal damage. Conclusive epidemiological evidence of the relationship has not been satisfactorily established. The case-control study reported here was undertaken to test the hypothesis that coeliac disease is linked to atopy. Eighty-two coeliac disease cases and a group of 180 age matched controls and all their first degree relatives were investigated for atopy. Siblings of cases reported an increased prevalence of food intolerance, compared to siblings of controls. No increase in asthma, eczema, rhinitis, conjunctivitis, cow's milk protein allergy (CMPA) were detected in relatives of cases, compared to those of controls. When each index case and each control were investigated no increased prevalence of atopic conditions was found. Skin prick testing to major allergens was positive in a similar proportion of cases and controls. Serum total IgE of a random sample of cases and controls showed no difference in mean values. This study supports the null hypothesis: there is no difference in the prevalence of atopy in cases affected by coeliac disease and their relatives, compared to controls and their relatives. The sources of possible bias in previous reports are discussed.

Membranous nephropathy associated with giant lymph node hyperplasia. A case report with histological and ultrastructural studies.

A young woman presented with nephrotic syndrome due to membranous nephropathy and a localized form of giant lymph node hyperplasia (Castleman's disease) occurring as a large intra-abdominal mass. Five months after surgical removal of the mass, only mild proteinuria persisted. Twenty months later a second kidney biopsy showed a near-normal morphology. Six years later the patient was free of symptoms and had normal urinalysis. Reviewing the pertinent literature, it seems to be the first case of a biopsy-proven cure of membranous nephropathy in a patient with membranous nephropathy and Castleman's disease.

Polyamine uptake by human colon carcinoma cell line CaCo-2.

The intracellular concentrations of the polyamines are highly regulated and high polyamine concentrations are associated with rapidly proliferating cells. Hormones, nutrients and growth factors that stimulate the proliferation of the intestinal epithelium, increase the intracellular polyamine concentration mainly by activating ODC expression. Other cell types stimulated to proliferate satisfy their requirement for polyamines by increasing polyamine uptake. In the present study, we investigated polyamine uptake by a human colon carcinoma cell line, CaCo-2. Uptake of putrescine, spermidine and spermine by CaCo-2 cells was saturable and temperature dependent and all polyamines appear to share a common carrier. The carrier of differentiated cells had an apparently higher affinity and lower activity than the carrier of replicating cells. Culture of CaCo-2 cells on porous filters showed that polyamine accumulation occurred mainly through the basolateral membrane in replicating cells, while an increase in the rate of apical uptake was observed after differentiation. A significant increase in polyamine uptake and in ODC expression resulted from fresh medium replacement, a well-known stimulus to proliferation; no change in uptake occurred after ODC inhibition by DFMO. We conclude that CaCo-2 cells are able to increase their polyamine concentration by both enhanced synthesis and increased polyamine uptake.

Regulation of diamine oxidase expression by ornithine decarboxylase in isolated rat small bowel enterocytes.

Ornithine decarboxylase (ODC) and diamine oxidase (DAO), enzymes involved in polyamine metabolism, are highly expressed by small bowel enterocytes. Modulation of ODC expression is mediated through cellular concentration of polyamines that inhibits the enzyme synthesis and also induces the synthesis of an inhibitory protein, the antizyme, which in turn binds to ODC and inhibits its activity. DAO is an important regulator of intracellular concentration of polyamines because it catalyzes the degradation of putrescine into gamma-aminobutyraldehyde. Change in intracellular polyamine concentration has been suggested to represent a regulatory factor for DAO expression. In order to investigate a possible regulation of DAO expression by ODC, we studied the effect of difluoromethylornithine (DFMO), a selective, irreversible inhibitor of ODC, on DAO activity in isolated rat small bowel enterocytes. Our data demonstrate that in isolated small bowel enterocytes ODC inhibition by 10 mM DFMO reduced DAO activity by 53%, suggesting that, in our experimental conditions, ODC plays a regulatory role on DAO expression.