vHnf1 regulates specification of caudal rhombomere identity in the chick hindbrain.

The homeobox-containing gene variant hepatocyte nuclear factor-1 (vHnf1) has recently been shown to be involved in zebrafish caudal hindbrain specification, notably in the activation of MafB and Kro x 20 expression. We have explored this regulatory network in the chick by in ovo electroporation in the neural tube. We show that mis-expression of vHnf1 confers caudal identity to more anterior regions of the hindbrain. Ectopic expression of mvHnf1 leads to ectopic activation of MafB and Kro x 20, and downregulation of Hoxb1 in rhombomere 4. Unexpectedly, mvhnf1 strongly upregulates Fgf3 expression throughout the hindbrain, in both a cell-autonomous and a non-cell-autonomous manner. Blockade of FGF signaling correlates with a selective loss of MafB and Kro x 20 expression, without affecting the expression of vHnf1, Fgf3, or Hoxb1. Based on these observations, we propose that in chick, as in zebrafish, vHnf1 acts with FGF to promote caudal hindbrain identity by activating MafB and Kro x 20 expression. However, our data suggest differences in the vHnf1 downstream cascade in different vertebrates.     

Palliative treatment of carcinomatous ascites with peritoneovenous shunt]

Carcinomatous ascites (CA) is not an uncommon manifestation of a metastatic neoplasia. The aim of this study was to evaluate the utility of peritoneovenous shunt (PVS) in patients with CA refractory to conventional management. Twelve patients in whom a PVS was placed with palliative intention were studied. One patient died in the postoperative period. Permanent control of the ascites was achieved in 7 (63.6%) of the remaining patients. PVS obstruction occurred in 4 patients (36.4%) and no other complications related to the shunt were seen. Results were better in CA of gynecological origin but without reaching significant statistical differences. We conclude that PVS can be useful for palliation of CA with a low complication rate.     

Quality of life during one year of postoperative prophylactic drug therapy after intestinal resection in Crohn’s patients: Results of the APPRECIA trial

Background

In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA).

Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway

Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, chromosome fragility, and cancer susceptibility. Eight FA-associated genes have been identified so far, the products of which function in the FA/BRCA pathway. A key event in the pathway is the monoubiquitination of the FANCD2 protein, which depends on a multiprotein FA core complex. In a number of patients, spontaneous genetic reversion can correct FA mutations, leading to somatic mosaicism. We analyzed the FA/BRCA pathway in 53 FA patients by FANCD2 immunoblots and chromosome breakage tests. Strikingly, FANCD2 monoubiquitination was detected in peripheral blood lymphocytes (PBLs) in 8 (15%) patients. FA reversion was further shown in these patients by comparison of primary fibro-blasts and PBLs. Reversion was associated with higher blood counts and clinical stability or improvement. Once constitutional FANCD2 patterns were determined, patients could be classified based on the level of FA/BRCA pathway disruption, as "FA core" (upstream inactivation; n = 47, 89%), FA-D2 (n = 4, 8%), and an unidentified downstream group (n = 2, 4%). FA-D2 and unidentified group patients were therefore relatively common, and they had more severe congenital phenotypes. These results show that specific analysis of the FA/BRCA pathway, combined with clinical and chromosome breakage data, allows a comprehensive characterization of FA patients.     

Polymorphonuclear elastase in the early diagnosis of complicated pyogenic pleural effusions

BACKGROUND: Polymorphonuclear elastase (PMN-E) is a neutrophilic marker that has been implicated in acute inflammatory responses. OBJECTIVES: To evaluate the accuracy of PMN-E in the diagnosis of complicated pyogenic effusions. PATIENTS AND METHOD: We studied 536 patients with pleural effusion of various etiologies. There were 125 pyogenic bacterial effusions (42 typical parapneumonic, 17 borderline complicated parapneumonic and 66 complicated parapneumonic or empyema), 83 tuberculous, 91 malignant, 42 paramalignant, 95 transudates, 28 miscellaneous and 72 effusions of unknown origin. Classic markers (pH, glucose, proteins, adenosine deaminase, LDH, leukocytes and differential count) and the PMN-E level were quantified in pleural fluid. The accuracy of PMN-E as an early marker in the diagnosis of complicated pyogenic infectious effusions was evaluated among pleural effusions that were not diagnosed with classic biochemical markers, radiological findings or Gram stain. Since results of pleural fluid culture and cytological examination are generally available after a 48-hour delay, they were not included as early markers in the initial diagnosis of pleural effusions. RESULTS: Early diagnosis of complicated pyogenic bacterial effusions was achieved in only 48 of 66 cases with classic markers. Among those that were not diagnosed with these parameters, a pleural PMN-E value >3,500 microg/l discriminated between complicated and noncomplicated pyogenic bacterial effusions with a sensitivity of 67% and a specificity of 97%. CONCLUSIONS: PMN-E is useful in the early diagnosis and management of complicated pyogenic infectious effusions, which may be delayed with classic markers.     

Prognosis Assessment of Cirrhotic Patients with Refractory Ascites Treated with a Peritoneovenous Shunt

Objective: The role of peritoneovenous shunt in the management of refractory ascites has not been clearly established. The aim of this study was to determine readily accessible predictive survival factors in cirrhotic patients with refractory ascites treated with a peritoneovenous shunt.
Methods: We studied a cohort of 100 cirrhotic patients with refractory ascites who underwent peritoneovenous-shunt placement in a university-based reference hospital.
Results: The estimated median survival of patients after shunt placement was 11 months (95% CI, 7-14 months). Multivariate analysis based on the proportional hazards model disclosed four independent variables associated with poor survival: high Pugh score, nonalcoholic etiology, low ascitic fluid protein concentration, and history of spontaneous bacterial peritonitis.
Conclusions: Mortality of cirrhotic patients treated with a peritoneovenous shunt can be determined by a prognostic index using four easily available variables. Such a prognostic index, once prospectively validated, could be used as an adjunct in planning treatment of cirrhotic patients with refractory ascites.     

Light and electron microscopic analysis of liver biopsy samples from rheumatoid arthritis patients receiving long-term methotrexate therapy

OBJECTIVE: We study liver damage in forty-two patients with rheumatoid arthritis (RA) using light (LM) and electron microscopy (EM) and assess histological changes after four years of treatment with methotrexate (MTX). PATIENTS AND METHODS: liver biopsies (LB) were taken before and after four years of treatment. Patients received weekly doses of between 7.5-15 mg of MTX. RESULTS: Fourteen per cent of the baseline LB presented mild perisinusoidal fibrosis (Roenigk IIIA) and the rest a lower Roenigk grade; EM identified an increase in collagen fibers in the Disse spaces in 50% of baseline LB. Neither microscopy technique revealed histological progression in any of the sequential LB. Variables that correlated with histological abnormalities were patient's age, length of evolution of the disease, alcohol consumption and biochemical data (gammaglutamate transferase and albumin); the cumulative dose of MTX was not correlated with worse histological findings. Correlation between the two microscopy techniques was good, though EM was more sensitive than LM for the detection of fibrosis. CONCLUSIONS: RA patients present with liver damage before treatment with MTX. The alterations are mild. At low doses MTX treatment is safe. In addition to the recommendations of the American College of Rheumatology, other factors associated with liver impairment are patient's age and length of evolution of the RA.