[Multidisciplinary approach in the management of intestinal failure]. / Tratamiento multidisciplinario del fallo intestinal.

OBJECTIVE: [corrected] Our aim was to analyze our results in the management of intestinal failure with a multidisciplinary approach including optimized parenteral nutrition, reconstructive surgery and intestinal transplantation (ITx). MATERIAL AND METHODS: We included all patients evaluated by our team with the diagnosis of IF. We assessed outcome, mortality and complications in children that achieved adaptation and those listed for ITx. RESULTS: Seventy one children (40 boys, 31 girls) were evaluated between 1997 and 2006 because of IF. Forty eight (76%) were referred from other institutions. In 56 cases (80%) IF began in the newborn period. Causes of IF were: short bowel syndrome (52) intestinal motility disorders (16) and intestinal epithelial disorders (3). Median birth weight in the group of SBS was 2.2 Kg and prematurity was an associated condition in 15% of them. Overall, fourteen patients (20%) achieved intestinal adaptation with progressive weaning from PN, the management of these children consisted of optimized parenteral and enteral nutrition and autologous intestinal reconstructive surgery. Nine (13%) are stable under home parenteral nutrition regimen. Eight children (11%), all of them listed for liver and small bowel transplantation, died in the waiting list after a mean waiting time of more than 300 days, with a median of 4 laparotomies and 4 episodes of catheter related sepsis. Four children (5.6%) died in the adaptation process or before their inclusion on the waiting list. Finally, twenty five (35,2%) children underwent 28 intestinal transplantation: 9 isolated small bowel transplantation (SBTx), 16 combined liver and small bowel (CLSB) and 3 multivisceral (MVTx). Among transplanted patients, 9 (36%) died, (3 MVTx, 1 SBTx and 8 CLSB) and four were retransplanted. CONCLUSIONS: Intestinal Transplantation is an established alternative to parenteral nutrition in the treatment of IF, although complications and mortality rates are still considerable, especially MVTx and CLSBTx. Mortality in children listed for intestinal transplantation remains also high. Intestinal adaptation can be achieved with adequate rehabilitation therapy even in some cases with apparently irreversible intestinal transplantation. Early referral before liver failure or other complications arise is crucial is crucial in order to improve the outcome of these patients.

[Crigler-Najjar syndrome: diagnosis and treatment]. / Síndrome de Crigler-Najjar: diagnóstico y tratamiento.

INTRODUCTION: Crigler-Najjar syndrome (CNS) is a very rare disease characterized by severe indirect hyperbilirubinemia from birth with normal liver function. It may cause kernicterus at any age. This disease is due to a total or partial deficiency of the UDP-glucuronosyltransferase enzyme caused by a mutation of the five exons of the ULT1A1 gene. PATIENTS AND METHODS: We reviewed the clinical outcomes of 7 children diagnosed with CNS between 1987 and 2004. RESULTS: There were three boys and four girls (two of which were homozygote twins). Two children had familial consanguinity. Three out of the six families had another healthy child. The mean follow-up was 8.3 years (14 months-17 years). In all patients, jaundice was detected in the first 3 days of life. The children were admitted to hospital between the fourth and the sixtieth day of life with jaundice and indirect bilirubin levels of between 12.5 and 32 mg/dl. In all patients, hemolysis was ruled out and hepatic function was normal. The diagnosis was based on genetic study in 4 patients, on inactive UGT enzyme in liver in 1 patient, and on clinical features exclusively in 2 patients. Treatment consisted of phenobarbital and phototherapy from 8 to 16 hours a day in all patients except three. Associated calcium salts were found in 5 patients and cholestyramine was found in two. Two patients developed kernicterus. Two underwent liver transplantation and bilirubin levels became normal. The remaining patients maintained indirect bilirubin from 15 to 25 mg/dl with no associated neurological alterations. CONCLUSIONS: Patients with CNS are at greater risk of developing kernicterus, mostly associated with indirect bilirubin levels of around 25 mg/dl. Phototherapy is very useful in these patients but the only definitive treatment is liver transplantation.

[Heparan sulfate: its kinetic effects on fibrinolytic-coagulative parameters after oral administration]. / Eparansolfato: cinetica degli effetti su parametri fibrinolitico-coagulativi dopo somministrazione orale.

The effects of the oral administration of 100 or 200 mg of heparan sulphate or placebo over time were assessed in nine healthy volunteers. Blood samples were collected at 1, 2, 4, 6, 8 and 12 hours after administration to assay prothrombin activity, partially activated thromboplastin time, and the activation to tPA and PAI-1. A significant increase (P < 0.001) of tPA activity and a reduced inhibition of fibrinolytic systems by PAI-1 were observed. These effects, which were clearly dose-dependent, appeared 2 hours after administration and persisted for 6-8 hours. On the contrary, no changes were recorded in coagulative tests at the doses used.

Liver triglyceride accumulation after chronic ethanol administration: a possible protective role of metadoxina and ubiquinone.

Hepatoprotective actions of metadoxina and ubiquinone have been studied in alcoholic rats by evaluating hepatic triglyceride accumulation and serum biochemical parameters of liver function. The two drug-treated groups displayed significantly lower triglyceride concentrations as compared to the ethanol-treated group. No significant differences were found among the two drug-treated and the control groups. Electron-microscopic abnormalities were found only in ethanol-treated rats. Serum biochemical parameters of liver function did not show any significant difference among all four groups. These results suggest a possible protective role of metadoxina and ubiquinone in ethanol-induced liver triglyceride accumulation.

[Ferroprotein succinylate: treatment of iron deficiency in obstetrics and gynecology]. / Il ferroproteinsuccinilato: terapia della carenza marziale in ostetricia e ginecologia.

Aim of this multicentric clinical trial was to evaluate the efficacy and tolerability of a new iron compound: iron proteinsuccinylate. 3,200 patients affected with iron deficiency due to obstetric or gynecologic etiology were treated with iron proteinsuccinylate, at a daily dose of 80 mg Fe3+, for at least 30 days. Iron proteinsuccinylate induced a statistically significant improvement (p less than 0.01) in mean values of hemoglobin and serum iron. The compound also caused a disappearance or improvement of subjective symptomatology (asthenia, anorexia) and of clinical conditions deriving from iron deficiency state (polypnea, cutaneous and mucous pallor). The treatment was well tolerated and caused a few slight side effects (diarrhea, epigastralgia, nausea) in 2.4% of patients.

[Heparan sulfate: efficacy and safety in patients with chronic venous insufficiency]. / Eparansolfato: efficacia e tollerabilità in pazienti affetti da insufficienza venosa cronica.

Fifty patients suffering from chronic venous disease were treated for 30 days with heparan sulphate 100 mg per os, b.i.d., or mesoglycan 50 mg per os, t.i.d., in a single blind random study. Both therapies led to a marked improvement in comparison to basal clinical values, but patients treated with heparan sulphate showed the greatest and most rapid regression of symptoms, associated with a significant improvement in plethysmographic index of capacitance and venous flow. Patients treated with heparan sulphate also showed an increased fibrinolytic activity and a reduced antithrombin III consumption, both of which were statistically significant.

Cyclosporine monitoring in the early post-transplant period in pediatric liver transplant recipients.

UNLABELLED: Monitoring of CsA blood levels two h post-dose (C2) has shown a higher correlation to drug exposure than monitoring of trough levels (C0) at least in adults, but initial doses and target blood levels of CsA have yet to be established in pediatric transplant patients. The objectives of the study were to describe the pharmacokinetics of CsA administered by NGT in the first days after transplantation and the dose of Sandimmun Neoral required to achieve minimum therapeutic range blood levels. This study included 20 pediatric liver transplant recipients (mean age of 3.2 yr) treated with CsA administered by NGT from day one post-transplant until they were able to ingest oral medication. The study was continued until one yr of post-transplant follow-up. Eight h pharmacokinetic profiles were performed on days one, three, and five post-transplant to determine the minimum dose required to achieve the therapeutic range. All children received an initial dose of 15 mg/kg/day of CsA by NGT. Mean CsA doses administered on days one, three, and five were 16.8, 29.5, and 36.5 mg/kg/day, respectively. Mean C0 levels of 119, 310, and 337 ng/mL and mean C2 levels of 213, 753, and 888 ng/mL were obtained. No correlation was found between C0 and C2 levels and the AUC(0-8 h). Intravenous administration of CsA was required in 55% of patients. The biopsy-confirmed acute rejection rate was 45%, with graft and patient survival rates of 95 and 100%, respectively. CONCLUSIONS: Poor absorption of CsA in small children requires a considerable increase in dose. CsA exposure cannot be estimated by single C0 or C2 determinations in the early post-transplant period.

[The demography of the Albanian minority in Calabria. First results]. / La demographie des minorites albanaises de Calabre. Premiers resultats.

PIP: Demographic changes in the population of Albanian origin in Calabria, located in southern Italy, are discussed. Using data from official Italian sources, the author examines the impact of international migration in the early 1900s and after World War II on this specific population. A decrease in population size, a lower birth rate, and an increased number of elderly people comprise the major demographic changes. (SUMMARY IN ENG AND ITA)^ieng

[The logit-linear transformation of Italian provincial life tables, 1971-1972]. / La trasformazione lineare logit delle tavole di mortalita provinciali italiane 1971-1972.

PIP: The main features of logit-linear transformation are first described. A model is then applied to obtain complete survivorship functions for Italian provincial life tables for 1971-1972. The results are compared with abridged life tables calculated by G. Caselli and V. Egidi using factor analysis. The use of the logit model in mortality projections is also considered. (summary in ENG, FRE)^ieng

[On methods for the rapid estimation of the synthetic indicator of fertility]. / Sui metodi di stima rapida di un indicatore conguinturale della fecondita.

Two methods that have been developed by G. Calot and E. Lombardo to provide quick estimates of synthetic measures of fertility from partial data are described and evaluated. The data used are for Italy for the period 1971 to 1980. "The results reveal that [the methods] are practically equivalent; however Lombardo's method is to be preferred because it also gives an estimate of age-specific fertility rates....[This method is then] applied to...national and regional Italian data in order to anticipate the age-specific fertility rates as well as the synthetic period measures for 1979 and 1980." (summary in ENG, FRE)

Immunological features of nonhealing midline granuloma.

A 60-year-old man affected by nonhealing midline granuloma (NHmG) is described. The histopathological features, the clinical course and the radiosensitivity of the lesion clearly differentiate this pathological condition from malignant lymphomas and from Wegener's granulomatosis (WG). The presence of antinuclear antibodies with an antinucleolar pattern in a subject bearing HLA-B8 suggests the involvement of autoimmune phenomena and a close relation between NHmG and WG.

Defective suppressor cell activity in essential mixed cryoglobulinemia.

Peripheral blood mononuclear cells from patients with essential mixed cryoglobulinemia were investigated for the ability to induce suppressor cell activity (S.C.A.) following in vitro exposure to Concanavalin A (Con A). The generation of Con A-S.C.A. is significantly impaired in essential mixed cryoglobulinemia compared to the healthy controls. No correlation was found between Con A-S.C.A. and the clinical or laboratory parameters of the disease. This impaired ability to induce Con A-S.C.A. in essential mixed cryoglobulinemia reflects a functional T-cell defect, which may play a role in the pathogenesis of the disease.

Anti-ribosomal ribonucleoprotein autoantibodies in systemic lupus erythematosus.

Sera from systemic lupus erythematosus (SLE) patients giving a fluorescent ribosomal pattern on tissue and cell preparations also showed precipitating autoantibodies against purified rat liver ribosomes. Ribosomal antigen is also present in rabbit thymus cellular extract (RTE), since the same sera gave precipitin lines against RTE in identity with ribosomes. Immunofluorescent staining was completely inhibited by serum absorption with ribosomes or with RTE. However ribosomal RNA and RNase or trypsin-treated ribosomes failed to react with these autoantibodies as demonstrated in immunoabsorption and immunodiffusion studies. These data suggest that these sera contain autoantibodies directed against some antigenic site composed of a portion of both RNA and ribosomal protein. Ribosomal autoantibodies were detectable at a low frequency in SLE patients characterized by an active disease and renal involvement.

Autoantibody pattern in non-A, non-B hepatitis.

Acute and convalescent sera from 44 patients with non-A, non-B hepatitis were tested for organ and non-organ specific autoantibodies by indirect immunofluorescence. In the acute-phase sera, 36.4% of the patients were positive for smooth muscle antibodies. Brush border antibodies and anti-reticulin antibodies were detected in 13.6% of the patients. Only two patients (4.5%) were positive for anti-nuclear antibodies. The autoantibody pattern did not relate to the different epidemiology, sex, a previous hepatitis B virus infection or to the biochemical liver function tests. The autoantibody pattern did not differ statistically in patients who recovered (23 cases) and in patients who progressed to chronic liver disease (21 cases), even if a higher frequency of smooth muscle antibodies was detected in the latter group. Convalescent sera screening showed that the clinical course of the disease did not relate to the behaviour of smooth muscle antibodies, brush border antibodies and anti-reticulin antibodies. However, an increase (28.6%) in anti-nuclear antibodies in patients who progressed to chronic liver disease was observed. The clinical significance of the presence of serological markers of autoimmunity in patients with chronic sequelae following acute non-A, non-B hepatitis is discussed.

Detection and further characterization of a newly described microsomal autoantibody associated with chronic delta infection.

Sera from 162 patients with acute or chronic hepatitis and from patients with autoimmune diseases have been investigated for autoantibodies by indirect immunofluorescence on human and animal tissues. A small proportion (14.2%) of young patients with chronic delta hepatitis has been found positive for cytoplasmic staining which was maximal in hepatocytes and renal proximal tubules. This autoantibody has been found to react with microsomal antigenic determinant different from the classic liver-kidney microsomal LKM antigen as demonstrated by fluorescence absorption experiments with purified subcellular organelles and by fluorescence-blocking tests. The microsomal autoantibody displayed also organ and species-specificity different from those shown by the LKM-positive sera. The positive patients showed persistence of the microsomal autoantibody during the follow-up without other serological markers of autoimmunity. There was no evidence of a particular course of chronic delta hepatitis in patients positive for the microsomal autoantibody.

In vivo immunopotentiating activity of thymopentin in aging humans: increase of IL-2 production.

The effect of thymopentin (TP-5) treatment on lymphocyte immune functions has been investigated in immunocompromised aged subjects. TP-5 was able to improve the cutaneous delayed hypersensitivity (CDH) to recall antigens and the proliferative response to phytohemagglutinin (PHA), concanavalin A, and Pokeweed (PWM) as well as the PHA-induced interleukin-2 (Il-2) production. On the other hand, no detectable changes were induced by TP-5 treatment either on PWM-induced immunoglobulin synthesis or on lymphocyte subsets identified by monoclonal antibodies. Our results suggest that the enhancement of Il-2 synthesis might be a crucial mechanism of the immunopharmacological action of TP-5 in aging humans.

[Echocardiography in primary hypothyroidism. Study of 25 patients]. / Aspetti ecocardiografici nell'ipotiroidismo primario. Studio di 25 pazienti.

25 patients affected by Primary Hypothyroidism and a control group of 25 subjects were studied with M-mode and Two-dimensional echocardiography. In hypothyroid patients mean left ventricular and aortic root dimensions were normal compared to control subjects. Pericardial effusion was found in 22 out of 25 patients (88%). Septal hypertrophy was found in 12 hypothyroid patients (48%), only in 3 out of these 12 patients left ventricular posterior wall hypertrophy was found. A moderate left atrial enlargement was found in 7 out of 25 hypothyroid patients. Two-dimensional echocardiography revealed an uniform degree of parietal hypertrophy from the basal segments to the cardiac apex. Therefore the main echocardiographic findings in hypothyroidism are: presence of pericardial effusion and asymmetrical septal hypertrophy. No correlations between these echocardiographic findings and age of patients, severity of "biochemical" alterations and duration of the thyroid disease was observed.

Altered expression of B lymphocyte surface immunoglobulins in minimal change nephrotic syndrome and focal glomerulosclerosis.

In 20 patients with nephrotic syndrome (10 minimal change glomerulonephritis, MCN; 10 focal glomerulosclerosis, FGS) the peripheral blood lymphocytes showed a statistically significant increase in IgG-bearing cells (SIgG-C) in comparison with 30 patients with other histological types of primary glomerulonephritis with and without nephrotic syndrome (14 and 16, respectively). In the same MCN and FGS patients the serum IgG levels were slightly decreased. Furthermore, 5 cases of MCN in sustained remission for 1 year after steroid therapy showed normalization of the SIgG-C and the serum IgG levels. The possible significance of these phenomena in the pathogenesis of the hypo-IgG-globulinemia in MCN and FGS is discussed.