DNA fragmentation is a feature of cystic fibrosis epithelial cells: a disease with inappropriate apoptosis?

Cystic fibrosis (CF) is a single-gene disease caused by mutations in the CFTR gene, which result in disrupted chloride secretions with inspissated mucous secretions by exocrine glands. Nick-end labelling was used to assess DNA fragmentation in 14 CF and 24 control duodenal samples, and in two CF and two control lung tissues. In CF small intestine median 46% (range: 30-82) villus enterocytes show DNA fragmentation (vs. 3% (range: 1-7) in controls P < 0.001) and median 37.5% (range: 23-79) crypt enterocytes show Ki67 antigen (P < 0.001). In CF airways 57% (range: 54-70) of epithelial cells show DNA fragmentation. Inappropriate high DNA fragmentation is a feature of various CF epithelia. This could have great impact in understanding the mechanisms leading to disease.

[Endoscopic sclerotherapy of esophageal varices]. / La sclerosi endoscopica delle varici esofagee.

Magnetic tape recordings of endoscopic images relating to pathologies with it is extremely important to follow morphological changes after treatment offer unquestionable advantages especially in the field of sclerosing endoscopic therapy for esophageal varices. This study--which was carried out using a 3/4 inch U-Matic videotape lasting 10 minutes--confirm the above statement. The criteria of selection for sclerosing techniques are illustrated according to the authors' personal evaluations made on the basis of experience accumulated during more than 10 years' activity; the results of modulated treatment are compared as both emergency and elective treatment, used as the single therapy or following deconnection or portosystemic derivation operations. The choices are confirmed by the number of successful outcomes, with only minimal and almost always easily controlled complications. This has led to the method's inclusion in clinical practice as yet another means of controlling hemorrhages due to portal hypertension, in addition to permitting a marked increase in the percentage of success following deconnecting and derivative operations performed in patients in better conditions of clinical compensation.

[Endoscopic surgery of the digestive system: state of the art. Opinion of an endoscopic surgeon]. / Chirurgia endoscopica dell'apparato digerente: stato dell'arte. L'opinione di un endoscopista chirurgo.

The Authors review the possible applications of surgical endoscopy in oesophageal, gastric, biliary, pancreatic and colic diseases. This critical assessment, performed under the abdominal endoscopic surgeon's point of view, is based on the overall experience of about 20 years of surgery, with particular regard to the sclerosis of oesophageal varices, neoplastic obstructions of oesophagus, biliary tract, colon and localized Laser treatment of neoplasms. Based on the results achieved, thanks to selective indications and monitoring by conventional surgical experience, the Authors conclude by staging a better reliability of the surgeon who performs surgical endoscopy to obtain good results after an accurate selection of those cases which can really benefit from endoscopic management.

[The natural history of allergy to eggs in atopic dermatitis]. / La storia naturale dell'allergia all'uovo nella dermatite atopica.

The outcome of atopic dermatitis and the incidence [correction of prevalence] of asthma was ascertained in a four-year follow-up in 47 children with eczema due to egg allergy. At the end of the study, skin lesions had cleared in 32 (68%) children. Of these, 18 (38.2%) developed tolerance to egg about two years after diagnosis, while 14 (29.7%) continued an elimination diet. Fifteen children (31.9%) are still affected by eczema due to discontinuation of the egg-free diet. At the end of follow-up, 23 children had presented at least three asthma episodes. Therefore, the incidence [correction of prevalence] of asthma in children with atopic dermatitis appears to be significantly higher when egg allergy is present. Egg allergy could be a marker of an atopic condition and therefore be an unfavourable prognostic signal as to the outcome of the disease and the appearance of respiratory allergy.

[Correlation of prick tests, RAST and food challenge tests in atopic dermatitis]. / Correlazione tra prick tests, rast e diete di scatenamento nella dermatite atopica.

Prick skin allergometry is actually accepted as the best test for the diagnosis of allergic disease, being reliable and not invasive. Nevertheless questions about it use in children have been put forward. The aim of this study is to evaluate the usefulness and the reliability of prick and Rast tests for the diagnosis of atopic dermatitis due to food allergy. The correlations between Prick and Rast have been studied as well as their relation to the food challenge test. Prick and Rast tests results overlay in almost all cases, while in only 25% of cases there has been copositivity between Prick & Rast and the food challenge. This finding confirms that the pathogenetic mechanism involved in A.D. due to food allergy is not only IgE mediated, but it may also require alternative immunoreactions. Although the prick test is a simple, cheap and reliable method, the diagnosis of food allergy cannot rely solely on it. The diagnostic and therapeutic approach to food allergy borne A.D. is based upon elimination diet and food challenges.

[Prevention of acute hypertensive encephalopathy in the course of acute post-streptococcal glomerulonephritis in children: considerations in 31 cases]. / La prevenzione dell'encefalopatia acuta ipertensiva in corso di glomerulonefrite acuta post streptococcica (GNAPS) nel bambino: considerazioni su 31 casi.

The authors analysed 31 cases of an acute hypertensive glomerulonephritis. The antihypertensive efficacy of two medicines: a vasodilator (dihidralazine) and a diuretic (Furosemide) was underlibed an these patients. Their efficacy was evident not only in the stabilization of P.A. around normal values on three days, but also on the disappearance of signs of on hypertensive encephalopathy whereas these ones were present.

[The prevention of allergic diseases with a hypoallergenic formula: a follow-up at 24 months. The preliminary results]. / La prevenzione delle malattie allergiche con formula H.A.: follow-up a 24 mesi. Primi risultati.

One hundred-eight infants from atopic families were admitted to the study. Each had at least one first-degree relative affected by asthma or rhinitis, conjunctivitis, eczema, cow's milk protein intolerance. All infants not breast fed were hypoallergenic formula. 46 infants were breast fed, 39 were bottle fed by the ordinary formula and 23 received the hypoallergenic one. No other food was introduced up to 6 months. Cow's milk proteins, egg, poultry and fish were introduced after 6 months. All infants were followed up to 24 months. Incidence of allergic diseases up to 24 months was not significantly different among the 3 groups.

[Erythrohemophagocytic lymphohistiocytosis. A clinical report of 3 cases]. / Linfoistiocitosi eritroematofagica. Contributo clinico di 3 casi.

Three infants suffering from hepatosplenomegaly, pancytopenia, hyperlipidemia, low fibrinogen levels and fever are reported. Two patients died during the first year of life, the third one received allogenic bone transplantation and survives. Clinical and haematological features are consistent with diagnosis of hemophagocytic lymphohistiocytosis.

[Elevated atrial natriuretic peptide (ANP) levels and normotension in Bartter's syndrome in childhood]. / Elevati livelli di peptide atriale natriuretico (ANP) e normotensione nella sindrome di Bartter dell'infanzia.

The authors describe a case of Bartter's syndrome, a variety of disease in the newborn, and they point out the most specific of the disease symptoms, that is the normal PA in presence of elevated plasma renin activity. So it was necessary to determine the ANP, the values of which, controlled for a period of 18 months, appeared above the normal ones. The authors conclude that this date would better explain the apparently contradictory date of the normotension.

[Atrial natriuretic factor in normal newborn infants and its effects on kidney function in anoxic syndrome and respiratory distress]. / Studio sul comportamento del fattore atriale natriuretico nei neonati normali e suoi effetti sulla funzionalità renale in corso di sindrome anossica e di distress respiratorio.

The Authors have studied 26 newborns suffering from anossic syndrome and/or respiratory distress. In them are valued as well as the renal function, also the behaviour of atrial natriuretic factor (F.A.N.). As a group of control 25 healthy and to term newborns were studied. In all subjects studied, but more specifically in the anossic, it became evident a net increase of F.A.N., which however was within the normal ranges about the 15th year of life. The Authors conclude that in normal newborn this behaviour of F.A.N. reflects the important circulation modification which is certified after birth, whereas in pathological newborns, in whom 69% of cases a functional renal failure is present, the increase of F.A.N. is not without significance in the shortening of time of re-establishment of renal function.

[Does the therapy with indomethacin interfere with growth in Bartter's syndrome in childhood?]. / La terapia con indometacina interferisce con l'accrescimento nella sindrome di Bartter dell'infanzia?

The authors describe a new-born form of Bartter's syndrome treated for about 6 years with Indomethacin in a quantity of 2 mg/Kg/die except short periods, during which it was given triamterene in a quantity of 2 mg/Kg/die. While with the first medicine the growth of height has had an average increase of about 9 cm a year, with the second one there hasn't been any result neither on growth nor on the rest of symptomatology. The A.A. on the base of recent experimental data think that the deficiency of height could be due to a scanty affinity of peripherical receptors and SmC, that could be removed from the provision of Indomethacin.

[Determination of the urinary secretion of beta 2-microglobulin combined with sequential renal scintigraphy using H123 for the early diagnosis of pyelonephritis in children]. / La determinazione dell'escrezione urinaria della beta 2 microglobulina associata alla scintigrafia renale sequenziale con H123 per la diagnosi precoce di pielonefrite nell'infanzia.

The acute pyelonephritis diagnosis in the infancy is often known very late or it is even underestimate that's why the general adopted criteria normally give no a certainty of the exact centre and the real damage entity. For this reason the authors have adopted a diagnostic protocol, which is based on the association of the urinary excretion dosage of beta 2 microglobulin, with sequential renal scan with Hippuran 123. In cases when the urinary beta 2 microglobulin was increasing, we could check a correspondent alteration of scintigraphic secretory phase. All that has permitted, in whale cases, of establishing with precision and at the right time the centre and the renal damage entity.

[Evaluation of kidney damage in neonatal anoxia syndrome: a 1-year follow-up]. / Valutazione del danno renale in corso di sindrome anossica neonatale: follow-up di un anno.

In thirty-three newborns with anoxic syndrome was valued the renal injury making use of usual parameters of renal function (Blood urea nitrogen, creatinine, FeNa, Clcr) and furthermore the rate of urinary excretion of beta 2-microglobulin, a marker of tubular damage. All the parameters at the beginning of follow-up were altered. Further monitoring of these showed that BUN, creatinine, FeNa, Clcr were normalized in a short time. Differently beta 2-microglobulin was altered up to the end of follow-up in thirty-one newborns; the values were much lower than original. These results show an high incidence of tubular suffering in the ischemic-anoxic syndrome and a tendency to protract in the time.

Antigliadin antibody, D-xylose, and cellobiose/mannitol permeability tests as indicators of mucosal damage in children with coeliac disease.

A dual sugar (cellobiose/mannitol) permeability test using an iso-osmolar solution was performed, to compare its ability to predict small-bowel mucosal damage in children affected by coeliac disease with the determination of serum levels of D-xylose and antigliadin antibody. Eighty-three children (67 on gluten-containing diet and 16 on gluten-free diet) were investigated. The D-xylose and the serum antigliadin antibody test predicted accurately 70% and 78% of the small-bowel biopsy results, respectively, whereas the cellobiose-mannitol permeability test predicted 93%. These data confirm the superiority of the permeability test over the D-xylose test, although the former cannot be advocated as a substitute for jejunal biopsy. Our results suggest a complementary use of the permeability test and the antigliadin antibody measurement as screening tests for coeliac disease before applying more invasive procedures.

Blockage of T-cell costimulation inhibits T-cell action in celiac disease.

BACKGROUND & AIMS: Celiac disease is an exemplary model of T cell-mediated pathology. Therefore, therapeutic approaches that target T cells may successfully control this disease. CTLA-4 immunoglobulin (CTLA-4Ig) can inhibit T-cell activation by blocking the engagement of CD28. We took advantage of this tool to define the pathogenic role of gliadin-specific T cells in the induction of celiac disease. METHODS: Duodenal biopsy specimens from 7 treated celiac patients were challenged in vitro with gliadin and CTLA-4Ig or CD40-Ig. After 24 hours, the biopsy specimens were analyzed for the presence of characteristic modifications induced by gliadin challenge. RESULTS: CTLA-4Ig down-regulated the expression of CD25, intercellular adhesion molecule 1, interleukin 2, and interferon gamma (stained lamina propria mononuclear cells/mm2; P < 0.05) induced by gliadin challenge, caused apoptosis of gliadin-specific T cells (apoptotic T cells/mm2; P < 0.05), and inhibited the production of antiendomysial antibody (P < 0.01). However, it did not control intraepithelial T-cell migration (P = NS) and Fas expression by enterocytes. Conversely, CD40-Ig only controlled production of antiendomysial antibody. CONCLUSIONS: In an organ culture model, CTLA-4Ig controls many but not all of the immunologic features of celiac disease.

In vitro activities of A-gliadin-related synthetic peptides: damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa.

BACKGROUND: Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have not been fully elucidated. Previous in vitro studies have suggested the presence of active sequences in the NH(2)-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31-55, 31-43, and 44-55 has been investigated. METHODS: Organ culture of jejunal mucosa from untreated and treated coeliac patients was used. In the first system enterocyte height was used as a measure of peptide toxicity; in the second system evidence of activated mucosal cell-mediated immune response was sought. RESULTS: Peptides 31-55 and 31-43 were active on untreated coeliac mucosa at a concentration of 0.5 mg/ml and peptide 44-55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31-55 and 31-43 at 1 mg/ml and peptide 44-55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molecules and the appearance of CD25 positive cells. CONCLUSIONS: Our results suggest that 31-43 and 44-55 A-gliadin peptides are both active, even if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.

Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients.

BACKGROUND & AIMS: Mucosal cell-mediated immune response is considered the central event in the pathogenesis of celiac disease. In cultured intestinal explants from celiacs in remission, we have characterized the early stages of gliadin-induced immune activation. METHODS: Intestinal biopsy specimens (15 treated celiacs and 13 controls) were cultured with gliadin or maize prolamine digests for 24 hours as well as for 1, 2, 4, 6, 8, and 12 hours in some subjects. The expression of immunologic markers was detected by immunocytochemistry. RESULTS: Gliadin challenge may initiate two parallel pathways, one of which leads to T-cell activation and another that precedes it. Epithelial cells overexpress DR molecules after 1 hour, and in a second stage T lymphocytes become fully activated. Moreover, T lymphocytes migrate in the upper mucosal layers. T lymphocytes that migrate in the higher lamina propria compartments are mainly CD4+ and show markers of activation; migrating intraepithelial lymphocytes are CD8+ and do not express these markers. CONCLUSIONS: In vitro gliadin challenge is a suitable model to reproduce various immunologic features of celiac lesions; these may be caused by different pathways. The comprehension of these phenomena is essential to clarify the distinctive pathogenic mechanisms leading to disease and may help in defining novel therapeutic approaches.