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Intestinal ischemia after abdominal aortic surgery is a highly lethal complication. In order to evaluate the pathogenesis, the diagnostic modalities and the best management, in a retrospective review, 12 patients undergoing postoperative small bowel or colonic ischemic lesions were identified between 1983 and 1995. Preoperative occlusion of IMA was present in nine patients, while a selective angiography of SMA demonstrated occlusive disease of peripheral branches in two asymptomatic diabetic patients. No patent IMA was ligated. When possible, hypogastric circulation was preserved by distal anastomosis into iliac bifurcation (4 cases). Postoperative leukocytosis or elevated LDH values were present. Colonscopy showed a suspected ischemic colitis in two patients and necrotic lesions in three cases. One patient died and diagnosis was made at autopsy. Nine patients were submitted to reoperation and a bowel resection with a proximal stoma was performed in seven of them. In two patients, the aorta or iliac artery below the proximal anastomosis and hypogastric artery suffered acute thrombosis, while prosthetic grafts were patent. A coagulation disorder caused thrombosis of intramural arterioles of the small bowel while peripheral branches of SMA were pulsatile. Eight of the patients submitted to relaparotomy died; non-operative management resulted in a left colon late stricture, while the remaining patient survived without sequelae. Overall mortality rate was 66.6%. Symptoms of this complication are not specific and diagnosis is delayed; consequently surgical repair is often unsuccessful. One patient with small bowel necrosis after elective AAA resection survived, which is extremely rare.

The renal damage consequent to cyclosporine A (CsA) administration ranges from hemodynamic alterations to irreversible chronic lesions. The initial vasoconstriction depends upon the imbalance between the various modulators of the renal vascular tone, among which the most powerful are endothelins and nitric oxide (NO). CsA could play a crucial role by inhibiting the Ca++/calmodulin-mediated activation of the constitutive NO synthase (NOS) isoform, which converts L-arginine (L-Arg) into NO and citrulline, with a 1:1 stoichiometry. To investigate the possibility of modulating CsA nephrotoxicity with L-Arg we studied six groups (G) of Lewis rats treated with daily gavage up to eight weeks: G1, CsA 40 mg/kg; G2, G1 plus L-Arg 300 mg/kg; G3, G2 plus the competitive inhibitor of NOS, NG-nitro-L-Arg (L-NNA); G4, L-Arg alone; G5, L-NNA alone; and G6, controls receiving vehicle alone. After eight weeks L-Arg treated rats were protected against the toxic effects of CsA [creatinine (Cr) values, G2, 0.62 +/- 0.05 mg/dl vs. G1, 0.99 +/- 0.16 mg/dl, P < 0.001; proteinuria (P), G2, 7.2 +/- 1.02 mg/day vs. G1, 15.1 +/- 1.9 mg/day, P < 0.01]. The administration of L-NNA abolished the protective effect of L-Arg (G3, Cr 1.23 +/- 0.16 mg/dl; P 16.9 = 2.3; P < 0.02 and P < 0.005, respectively vs. G2). The levels of Cr in G2 rats were superimposable to control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

This multicenter study investigated the characteristics of circulating IgA molecules in 77 children: 42 had primary IgA nephropathy (IgAN), 20 were non-IgA glomerulonephritides (CGN) and 15 had urological problems (U). Fifteen assays were employed including the detection of macromolecular IgA [IgA immune complexes (IgAIC) by the conglutinin (K) assay, heavy molecular weight IgA in 2.5% polyethylene glycol (PEG), mixed IgA/IgGIC (Jacalin assay), IgA-Fibronectin (IgA-F) aggregates]IgA antibodies to alimentary antigens (gliadin, glycgli, glutein, ovalbumin, bovine serum albumin) and IgA binding to mesangial antigens (fibronectin, laminin, type IV collagen) or polycations (poly-L-lysine). Total IgA and IgA reacting with jacalin, supposed to bear an altered galactosylation, were measured as well. Mean levels of each kind of macromolecular IgA were significantly increased in children with IgAN in comparison to U disease (K-IgAIC p < 0.05, PEG-IgAIC p < 0.01, IgA/IgGIC p < 0.004, IgA-F aggregates p < 0.0003). However, IgA-F were the only macromolecular IgA significantly higher in IgAN than in CGN (p < 0.0005). IgA-F aggregates did not correlate with any urinary sign of activity, while K-IgAIC data were significantly related with microscopic hematuria (p < 0.05) and past history of gross hematuria (p < 0.02). Children with IgAN had mean levels of IgA reacting with the lectinic fractions of gliadin significantly higher than CGN (p < 0.01) and U groups (p < 0.003). IgAN displayed an enhanced production of IgA reacting with mesangial matrix components vs CGN (p < 0.03) and U (p < 0.0003) groups and showed altered interactions with positively charged molecules (poly-L-Lysine, p < 0.01) and carbohydrate residues (jacalin p < 0.05). In IgAN there is an increased circulation of altered IgA favouring the formation of macromolecular IgA, including true IgAIC or IgA aggregated by carbohydrate interactions. The affinity for the mesangial matrix glycoproteins and for the mesangial area electrical charge might further enhance the trapping and deposition of the immune material containing IgA. IgA-F aggregates seem to be a marker of this event, while complement binding molecules in IgAIC correspond to the hematuric manifestation of the nephritogenic process.

From 1981 to 1992, 81 children affected by idiopathic nephrotic syndrome were treated in our Division. The majority were males (74%), with mean age at diagnosis of 4.8 (0-14)) years. They had a mean follow-up of 5.7 (0.5-11) years. The renal function at diagnosis was normal in all cases, proteinuria was selective in 86.4% of the cases. 28 children with somehow atypical behaviour underwent renal biopsy. In this negatively selected group the more frequent histologic forms were focal segmental glomerular sclerosis (33.5%), minimal change disease (37.4%), IgM mesangial glomerulonephritis (16.6%), membranous nephropathy (12.5%). First choice drug was in all cases prednisone. In the last years the trend for steroid therapy was to adopt long protocols (16 weeks), with a total dose of 105-133 mg/kg per therapeutic cycle. About 90% of children had a favourable response to steroids, but half of them were frequent relapser. In these cases the long term stable remission was obtained with steroids alone in 10.8% of the cases, with the association of cyclophosphamide in 62%. In a minor fraction and in the steroid resistant (13.6% of the total cases) levamisol and cyclosporin were also adopted. 2.4% of the cases progressed to end stage chronic renal failure. Most of the steroid sensitive children were in remission after 3-4 years of disease, only 6% relapsed more than 5 years after diagnosis.

It is generally thought that in primary IgA nephropathy (IgAN) an altered immune response favours high levels of serum IgA directed against environmental or mesangial antigens (Ag) leading to circulating IgA containing immune complexes (IgAIC). The aim of this multicenter collaborative study was to evaluate some of the IgA immunologic abnormalities in children with IgAN. We investigated 42 children with biopsy-proved IgAN, 21 children with non-IgA glomerulonephritides (CD) and 15 with previous urologic disorders without any evidence of immunologic disease (U). The following methods were used: detection of macromolecular IgA (IgAIC by the conglutinin solid-phase assay, heavy MW IgA measured in 2.5% polyethylene glycol precipitate, IgA-fibronectin aggregates, mixed IgA-IgGIC); serum levels of IgA to alimentary Ags (gliadin, glyc-gli, ovalbumin, bovine serum albumin) and mesangial Ags (fibronectin, laminin, type IV collagen) and reactivity of IgA with the lectin jacalin. In children affected with IgAN serum levels of macromolecular IgA were significantly higher in comparison to U group (p < 0.05-p < 0.0005). IgA-fibronectin aggregates only were significantly higher also than CD group (p < 0.0005). Mean levels of antigliadin IgA were significantly higher in IgAN than in controls (CD p < 0.01 and U p < 0.03) and similar data were found for IgA to mesangial matrix (laminin and fibronectin), which were significantly greater in IgAN than in CD and U (p < 0.01-p < 0.0002). Serum IgA in children with IgAN showed a greater affinity for both polycations and glycosylated molecules. Children affected by IgAN present abnormalities in serum IgA similar to those observed in adults with the same disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral immunization with gliadin (GLI) can induce immunoglobulin A mesangial deposits (IgA nephropathy [IgAN]) in mice. A role for GLI in human IgAN has been inferred from an association with celiac disease, increased serum anti-GLI IgA in patients with IgAN, and benefit from a gluten-free diet observed in some IgAN patients. These effects might be due to the antigenic or lectinic properties of GLI. The aim of our study was to investigate whether GLI binding to glycosylated residues (ie, lectinic activity) favors binding of GLI to cultured rat mesangial cells, bridging IgA macromolecules. We also sought to determine whether GLI binding alters mesangial cell function. Gliadin binds to rat mesangial cells in the third and fourth passages, as determined by immunofluorescence. Gliadin binding is inhibited by co-incubation with 1 mol/L N-acetyl-D-glucosamine and 1 mol/L alpha-D-mannose, sugars competitive for this lectinic bond. Quantification by biotinylated GLI revealed a significant dose-dependent binding of GLI (P < 0.001) inhibited by N-acetyl-D-glucosamine (P < 0.05). Some saccharolytic enzymes, like invertase, modify the cell surface to decrease GLI binding (P < 0.02). In addition, GLI promoted the binding of purified mouse polymeric IgA to mesangial cells. The binding of GLI to mesangial cells modulates arachidonic acid metabolism by cultured mesangial cells, significantly inhibiting prostaglandin E2 production (P < 0.02), increasing synthesis of thromboxane B2 (P < 0.01) and tumor necrosis factor (P < 0.001), but not interleukin-1 beta. These responses were abrogated by co-incubation with N-acetyl-D-glucosamine and/or pretreatment with invertase. Non-immune binding of an environmental alimentary lectin, GLI, to mesangial cells in culture might favor the binding of IgA and IgAIC to mesangial cells, enhancing both IgA mesangial trapping and in situ IgA deposit formation. This could occur via GLI-specific antibodies or by virtue of the binding of nonspecific IgA on a lectinic basis, or both. Moreover, related changes in eicosanoid synthesis might stimulate mesangial cell growth and mesangial matrix production, together with mesangial cell contraction, contributing to the pathogenesis of IgAN.

Reflux nephropathy is an important cause of chronic renal failure in children. After the parenchymal scar, the progression is thought to be mediated by glomerular hypertension in remnant nephrons resulting in modifications in permselectivity to macromolecules. Proteinuria correlates with a progressive course. The glomerular permselectivity to macromolecules in basal conditions and after acute hemodynamic stress was investigated in 28 children whose bilateral vesico-ureteric reflux (VUR) had been previously surgically corrected (meanly 5.6 years before) and with normal creatinine clearance (CrCl). Bilateral renal scarring (0 to 8 scale for both kidneys) was 4.3 +/- 1.6. Albuminuria (UAE) was evaluated in basal conditions and under acute hyperfiltration induced by amino acid (Aa) infusion. After isotonic saline at 310 ml/hour/1.73 m2, 6 mg/kg/min of Aa were infused for 2 hrs. UAE was significantly higher than controls in basal conditions (p < 0.01), and further increased after Aa infusion (p < 0.02). Microalbuminuria was detectable in 53.5% of the children in basal conditions and in 64.3% after Aa. Also urinary beta 2 microglobulin significantly increased at the end of the test (p < 0.001). CrCl significantly increased at the first hour (p < 0.05). Children with severe renal parenchymal scarring had greater UAE (p < 0.01) and beta 2M (p < 0.02) values after provocative test than those with mild renal damage. In 8 children GFR and ERPF were measured by means of inulin and p-hippurate clearance respectively. The variations in UAE during Aa infusion were significantly correlated with GFR dynamics (p < 0.05) while they were not influenced by ERPF modifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute renal failure is a frequent and dramatic clinical syndrome, producing a wide variety of serious and potentially lethal disorders in infancy. Review of 30 cases of severe acute renal failure occurred from 1985 in our unit reveals that the major causes are: acute tubular necrosis (33%), hemolytic uremic syndrome (16%), post-streptococcal glomerulonephritis (16%). 16 patients aged from 7 days to 15 years weighing 2 to 59 kilos, underwent dialysis: 8 HD, 7 PD, 1 both. Functional recovery occurred in 13 patients (82%); 3 patients died for the condition that precipitated renal insufficiency.

This is the first of a series of reports on diabetic neuropathy. Peripheral or somatic diabetic neuropathy is discussed with reference to its major symptoms: central, peripheral and amyotrophic mononeuropathies, symmetrical and asymmetrical polyneuropathies, peripheral arthropathy and finally diabetic cachexia. The various theories on the pathogenesis of peripheral neuropathy are presented. Finally data on 173 type I and II diabetics are presented. These patients, treated in outpatients departments, were paired by sex, weight and age with an equal number of non-diabetic subjects. The results of the survey largely confirm report in the literature. The importance of continuous medical surveillance for the identification and hence prevention of diabetic neuropathy is emphasized. This is particularly necessary since we have still much to learn about the natural history of the disease and for the moment the therapeutic approaches to the various neuropathies concerned are both tentative and symptomatic.

In 9 healthy subjects we evaluated the effect of a constant ranitidine infusion (100 mg) on glucose (mg/dl), insulin (microU/ml) and C-peptide (ng/ml) serum levels promoted by oral glucose tolerance test (75 g). Ranitidine significantly increased the area under concentration/time curves for glucose and insulin but not that of C-peptide. Our data indicate that ranitidine does not affect pancreatic insulin release nor peripheral glucose utilization and are consistent with the hypothesis that ranitidine influences the hepatic clearance of glucose and insulin both of which undergo high first-pass liver extraction.

Ten healthy subjects have been given before and after treatment with phenobarbital the following intravenous charges: a) nicotinic acid; b) rifamicyn-SV; c) simultaneous administration of the two drugs. Along with confirmatory evidence of the wellknown increase in bilirubinaemia (prevalently unconjugated), we have observed phenobarbital to attempts partially yet significantly that effect. On the base of direct experience on rat liver, we hypothise phenobarbital to increase the pool of the Y protein carrying cholephilic organic anions into the hepatocytes.

The emergency treatment of bleeding esophageal varices still remain a very difficult problem. In this report results obtained with conservative and operative procedures will be compared. In particular 32 patients underwent transhepatic occlusion of the gastric vessels feeding varices, and 8 patients (total experience 27 cases) to emergency esophageal transection with the EEA stapler instrument. The conclusion is that both methods represent useful alternatives, in selected cases, rather than being antagonists.

The influence of treatment with allopurinol (5 mg/kg/die for 15 days) on T/2 of tolbutamide and rifomycin-SV intravenously administered, has been studied in 10 healthy volunteers. We have observed reduction of T/2 of tolbutamide and, on the contrary, prolongation of T/2 of rifamycin-SV. Tolbutamide behaviour was unexpected, considering that other Authors had previously found inhibition of metabolic degradation of other drugs metabolized by the microsomal enzymes. We conclude that data concerning the influence of a drug (in our case, allopurinol) on the metabolism of another drug cannot always authorize general deduction and previsions regarding the metabolic interferences on the pharmacokinetics of other substances.

Development of diabetes mellitus is a common complication of side to side porta-caval anastomosis (PCA). Five patients with liver cirrhosis and portal hypertension have been studied with intravehous (IVGTT, 0,5 g/Kg B.W.) and oral (OGTT, 1 g/Kg B.W.) glucose tolerance tests before and three weeks after PCA. Fasting plasma glucose was 84 +/- 7 before and 87 +/- 3 mg/dl after PCA. Fasting IRI increased from 17 +/- 3 to 31 +/- 6 microU/ml. The pattern of plasma glucose and IRI response to IVGTT did not change after PCA. Plasma glucose resonse to OGTT after PCA showed only an earlier rise at 60 instead of 90 minutes, whereas IRI resonse (area under the insulin curve) was significantly enhanced (from 12.4 to 19.8 U/l, p < 0.05). These data suggest a role of gut polipeptides in determining hyperinsulinemia and insulin resistence in PCA patients.

Autonomic diabetic neuropathy of the alimentary canal takes several basic forms: a) oesophagopathy , b) gastroparesis, c) enteropathy, d) bile duct disorders. In many cases three are no subjective symptoms. In other the onset of the clinical condition may take acute and dangerous forms as in gastropathy. In still other cases e.g. enteropathy, the neuropathy may develop in bizarre and unexpected ways which are highly damaging to the patient's quality of life though in most cases they are not fatal. Bile disorders involving minimal motility after stimulus, as in denervation and reduced sensitivity to pain are particularly significant. Diabetics are more likely to suffer from calculosis (59.6% of cases), with septic complications (20% in diabetics compared to 7.8% in non-diabetics) or cholestasis (20% in diabetics v. 15.8% in non-diabetics). These figures indicate that all diabetics and especially the elderly should be subjected to careful examination to identify any bile disorders.