An index with improved diagnostic accuracy for the diagnosis of Crohn's disease derived from the Lennard-Jones criteria.

BACKGROUND: The Lennard-Jones criteria are considered the gold standard for diagnosing Crohn's disease (CD) and include the items granuloma, macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates and discontinuous inflammation on histology. The criteria have never been subjected to a formal validation process. AIM: To develop a validated and improved diagnostic index based on the items of Lennard-Jones criteria. METHODS: Included were 328 adult patients with long-standing CD (median disease duration 10 years) from three centres and classified as 'established', 'probable' or 'non-CD' by Lennard-Jones criteria at time of diagnosis. Controls were patients with ulcerative colitis (n = 170). The performance of each of the six diagnostic items of Lennard-Jones criteria was modelled by logistic regression and a new index based on stepwise backward selection and cut-offs was developed. The diagnostic value of the new index was analysed by comparing sensitivity, specificity and accuracy vs. Lennard-Jones criteria. RESULTS: By Lennard-Jones criteria 49% (n = 162) of CD patients would have been diagnosed as 'non-CD' at time of diagnosis (sensitivity/specificity/accuracy, 'established' CD: 0.34/0.99/0.67; 'probable' CD: 0.51/0.95/0.73). A new index was derived from granuloma, fibrosis, transmural inflammation and macroscopic discontinuity, but excluded lymphoid aggregates and discontinuous inflammation on histology. Our index provided improved diagnostic accuracy for 'established' and 'probable' CD (sensitivity/specificity/accuracy, 'established' CD: 0.45/1/0.72; 'probable' CD: 0.8/0.85/0.82), including the subgroup isolated colonic CD ('probable' CD, new index: 0.73/0.85/0.79; Lennard-Jones criteria: 0.43/0.95/0.69). CONCLUSION: We developed an index based on items of Lennard-Jones criteria providing improved diagnostic accuracy for the differential diagnosis between CD and UC.

Candida esophagitis as the cause of swallowing disturbances in an 85-year-old patient with myasthenia gravis.

An 85-year-old man with myasthenia gravis was successfully treated with methotrexate (10 mg/week), pyridostigmine and prednisolone (0-30 mg/day) for over 10 years. Then, he developed dysphagia and lost weight. Gastroscopy revealed Candida esophagitis. The patient received nystatin for 2 weeks. Methotrexate was stopped, and immunosuppressive therapy was continued with prednisolone alone. The patient has now remained in good condition for over 1 year. Although dysphagia is a typical symptom of myasthenia gravis, swallowing disturbances should not be attributed hastily to this disease, since they may also be a complication of therapy.

Aggregation of truncated GST-HD exon 1 fusion proteins containing normal range and expanded glutamine repeats.

We have shown previously by electron microscopy that the purified glutathione S-transferase (GST)-Huntington's disease (HD) exon 1 fusion protein with 51 glutamine residues (GST-HD51) is an oligomer, and that site-specific proteolytic cleavage of this fusion protein results in the formation of insoluble more highly ordered protein aggregates with a fibrillar or ribbon-like morphology (E. Scherzinger et al. (1997) Cell 90, 549-558). Here we report that a truncated GST HD exon 1 fusion protein with 51 glutamine residues, which lacks the proline-rich region C-terminal to the polyglutamine (polyQ) tract (GST-HD51 delta P) self-aggregates into high-molecular-mass protein aggregates without prior proteolytic cleavage. Electron micrographs of these protein aggregates revealed thread-like fibrils with a uniform diameter of ca. 25 nm. In contrast, proteolytic cleavage of GST-HD51 delta P resulted in the formation of numerous clusters of high-molecular-mass fibrils with a different, ribbon-like morphology. These structures were reminiscent of prion rods and beta-amyloid fibrils in Alzheimer's disease. In agreement with our previous results with full-length GST-HD exon 1, the truncated fusion proteins GST-HD20 delta P and GST-HD30 delta P did not show any tendency to form more highly ordered structures, either with or without protease treatment.

[Nephrotic syndrome refractory to conventional therapy]. / Sindrome nefrosica refrattaria alla terapia convenzionale.

BACKGROUND: Prednisone is the choice medicine in Nephrotic Syndrome (NS) treatment, possibly associated with immunosuppressor medicines (cyclophosphamide or chlorambucil), either in case of NS resistance at cortisone therapy or with frequent relapses. Cyclosporin A (CyA) use has been recently proposed, due to its inhibitory effect on the IL2 and lymphokine release, with a permeabilizing effect on the glomerular membrane. The purpose of this study is to evaluate the CyA antiproteinuric effectiveness with NS conventional therapy refractory patients. METHODS: Six patients (3 females and 3 males) have been treated with CyA (4 +/- 0.5 mg/Kg/die) associated with low corticosteroid dosages. RESULTS: During the treatment, proteinuria reduced in 5 patients, at less than 1/3 of pre-treatment values, for 4 patients this happened starting from the 2nd month of therapy, while after the 12th for the fifth patient. The sixth patient has now a 2/3 reduction compared to the initial one and he is at the 3rd month of therapy. During the CyA treatment, further to the proteinuria reduction, a total proteinemia values increase and a cholesterolemia and tryglyceridemia reduction has been observed, while creatinine and PA have not changed. CONCLUSIONS: Four out of the six treated patients have been respectively under therapy for 2,3,12,30 months. Two stopped CyA therapy: one after 18 months due to clinical stability, still present after 2 years from interruption; one after 9 months with a stable clinical picture for just three months, since she was longing for a pregnancy, achieving a quick proteinuria relapse.

Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntington's disease pathology.

Huntington's disease is a progressive neurodegenerative disorder caused by a polyglutamine [poly(Q)] repeat expansion in the first exon of the huntingtin protein. Previously, we showed that N-terminal huntingtin peptides with poly(Q) tracts in the pathological range (51-122 glutamines), but not with poly(Q) tracts in the normal range (20 and 30 glutamines), form high molecular weight protein aggregates with a fibrillar or ribbon-like morphology, reminiscent of scrapie prion rods and beta-amyloid fibrils in Alzheimer's disease. Here we report that the formation of amyloid-like huntingtin aggregates in vitro not only depends on poly(Q) repeat length but also critically depends on protein concentration and time. Furthermore, the in vitro aggregation of huntingtin can be seeded by preformed fibrils. Together, these results suggest that amyloid fibrillogenesis in Huntington's disease, like in Alzheimer's disease, is a nucleation-dependent polymerization.

[Heart failure resistant to drug therapy. Nephrologic approach]. / Scompenso cardiaco resistente ai farmaci. Approccio nefrologico.

BACKGROUND: The congestive heart failure (IV cl. NYHA) refractory to medical therapy, can be treated with ultrafiltrative method such as extracorporeal ultrafiltration (UF), intermittent veno-venosus hemofiltration, intermittent peritoneal dialysis (IPD) or chronic ambulatory peritoneal dialysis (CAPD). METHODS: Sixty-one patients suffering from SCC have been managed by combining medical therapy with ultrafiltrative treatment. RESULTS: 28% (17 patients) died within a week from ultrafiltrative therapy beginning. 39% (24 patients) took up to respond to medical therapy (responders). 33% (20 patients) didn't give a proper response to pharmacological therapy (non responders), therefore a ultrafiltration program with chronic ambulatory peritoneal dialysis (CAPD) has been undertaken. Among ultrafiltrative methods applied to patients, IVVH is the most effective. Clinical parameters analysis, relevant to dehydration acute phase, points out: an evident loss of corporeal weight between dehydration pre-post phases in all 3 groups, with statistically significant results; a SAP values reduction between the beginning and the end of treatment in all 3 groups; a PAD values reduction in the group of deceased and non responders. This value remains stable in responders group. Non responders patients, inserted in a ultrafiltration program with CAPD present the following survival rate: 55%: 6 months; 35%: 1 years; 15%: 4 years. These patients maintain a good self-management in 50%, sufficient in 35% and totally partner-dependent in 15%. CONCLUSIONS: Ultrafiltration method together with pharmacological therapy allows a resetting of neuro-endocrine and electrolytic system in refractory congestive heart failure patients and a recovery of a pharmacological response. Without such a response a cardio-circulatory balance can be maintained through a CAPD method.

[Peritoneal dialysis and chronic dobutamine, two experiences contrasted. Possible role and indications in refractory cardiac decompensation]. / Dialisi peritoneale e dobutamina cronica, due esperienze a confronto. Possibili ruoli ed indicazioni nello scompenso cardiaco refrattario.

UNLABELLED: The number of patients who develop heart failure (HF) is increasing and is expected to increase further in the next decade. Despite the availability of an ever-widening array of pharmacological therapy, patients with end-stage HF have a poor long-term prognosis. Little attention has been paid to alternative non-conventional therapy for these patients. The aim of this non-randomized study was to describe two non-conventional approaches in patients with HF, refractory to conventional medical therapy. The feasibility and long-term efficacy of a continuous ambulatory peritoneal dialysis (CPAD: 20 patients) or dobutamine intermittent infusions (DOB: 11 patients) was analysed: the mean dobutamin dose was 5 gamma/kg/min, and the interval period treatment ranged from 12 hours/day to 12 hours/week. RESULTS: Both treatments were feasible and non major procedure complications occurred. The 6 and 12 month survival rates were 55% (14/20 patients), 35% (9/20 patients) and 36% (6/11 patients), 18% (3/11 patients) in the CAPD patients and DOB patients, respectively. All patients survived at one year (38% = 12/31 patients) documented a significant functional improvement and quality of life. The conclusions is drawn that the use of CAPD and DOB should be considered in those with refractory HF, in whom medical therapy has failed and in whom home training is considered feasible. Further studies are necessary to define those patients who will benefit from one of these strategies and to confirm these preliminary data.

[Medical nephropathies: what has changed in 20 years]. / Nefropatie mediche: cosa è cambiato in 20 anni.

The authors analyse the series of patients with medical nephropathy undergoing renal biopsy between 1973 and 1993 in order to make a diagnostic and prognostic comparison between the first (ID) and second (IID) decade. Clinical indications for biopsy, which became more precise during the second decade, led to the diagnosis of fewer patients with normal histology; the introduction of ME and IF allowed non-significant histological conditions to be reduced during IID; echo-guided biopsy has led to a reduced number of post-biopsy complications in IID compared to ID. Epidemiological analysis reveals the reduction of focal glomerulosclerosis in IID in favour of glomerulonephritis with IgA deposits in correlation with the use of IF; the increase in mebranous glomerulonephritis secondary to increased antigenic stimuli; reduced acute post-infective glomerulonephritis and membrane-proliferative glomerulonephritis owing to an improved prophylaxis of sources of infection. Among the patients undergoing renal biopsy and commencing dialysis an increase was observed in IID in the number of cases of membranous glomerulonephritis or caused by IgA deposits. There was an increased interval between biopsy and the start of dialysis in IID compared to ID, in spite of fewer patients receiving immunosuppressive therapy. This was probably due to the increased number of pathologies with a slower evolution, thus justifying the postponement of the start of dialysis.

[High-efficiency membranes and the dialysis solution]. / Membrane ad alta efficienza e bagno di dialisi.

During this work through the total bacterial count and of the pseudomonas and the determination of the positive substances to Limulus Amebocyte Lysate test, bacterial pollution of the liquid bicarbonate concentrate has been determined together with the influence that preparation conditions and the entity of interval between the said preparation and utilization of concentrates have on it. Through the evaluation of the cardiac rate and the systemic arterial pressure, we have studied the influence of the bacterial pollution on the clinical of the patient. Analysing the obtained data we can point out that the liquid bicarbonate concentrate present an elevated degree of contamination which feels the effects of the production and storage procedures. The remark of inverse correlation between systemic arterial pressure and endotoxin level of the dialysate seems to reconfirm the importance of the bacterial contamination on the clinical of the patient.