Magnetic resonance imaging (MRI) simulation on EGEE grid architecture: a web portal design.

In this paper, we present a web portal that enables simulation of MRI images on the grid. Such simulations are done using the SIMRI MRI simulator that is implemented on the grid using MPI and the LCG2 middleware. MRI simulations are mainly used to study MRI sequence, and to validate image processing algorithms. As MRI simulation is computationally very expensive, grid technologies appear to be a real added value for the MRI simulation task. Nevertheless the grid access should be simplified to enable final user running MRI simulations. That is why we develop this specific web portal to propose a user friendly interface for MRI simulation on the grid. The web portal is designed using a three layers client/server architecture. Its main component is the process layer part that manages the simulation jobs. This part is mainly based on a java thread that screens a data base of simulation jobs. The thread submits the new jobs to the grid and updates the status of the running jobs. When a job is terminated, the thread sends the simulated image to the user. Through a client web interface, the user can submit new simulation jobs, get a detailed status of the running jobs, have the history of all the terminated jobs as well as their status and corresponding simulated image.

Influence of esophagojejunostomy on the induction of adenocarcinoma of the distal esophagus in Sprague-Dawley rats by subcutaneous injection of 2,6-dimethylnitrosomorpholine.

To study the influence of reflux esophagitis on the carcinogenic response of 2,6-dimethylnitrosomorpholine (2,6-DMNM), an experiment was designed, composed of 6 groups of 8-week-old Sprague-Dawley rats, each consisting of 20 males and 20 females. Group 1 served as untreated controls. All animals of groups 2, 4, and 6 underwent an esophagojejunostomy with gastric preservation to produce a chronic reflux esophagitis. 2,6-DMNM was injected s.c. once weekly for life at doses of 1/100 and 1/10 of the 50% lethal dose to groups 3 and 4 and groups 5 and 6, respectively. Carcinogen exposure began in groups 4 and 6 15 days after the esophagojejunostomy. Squamous cell carcinomas were observed in the esophagus of 36 animals, mainly in those receiving the higher dose. Exophytic squamous cell carcinomas, a variety rarely seen in humans, were mostly seen in the groups receiving 2,6-DMNM alone, whereas endophytic squamous cell carcinomas, the variety most frequently seen in humans, mainly developed in the groups receiving the combined treatment. In addition adenocarcinomas with abundant mucin production were found in the distal esophagus of 23 animals. They were found exclusively in animals of groups 4 and 6 which underwent esophagojejunostomy plus 2,6-DMNM exposure. No adenocarcinomas were encountered in groups without experimental reflux esophagitis. These findings may contribute to further understanding of the association between reflux esophagitis and the various histological types of esophageal carcinoma in humans.

Positive results of adjuvant mitomycin-C in resected gastric cancer: a randomised trial on 134 patients.

In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a randomised trial on 134 patients in two arms: a control one with no further treatment after surgery versus a treatment arm given mitomycin-C (MMC), 20 mg/m2 intravenously one day every 6 weeks for four courses, starting before the sixth week after surgery. The median follow-up was 105 months. In the control arm, 49 out of 66 patients died due to recurrence, versus 40 out of 68 patients in treatment arm. Actuarial survival curve was statistically significant (P < 0.025) in favour of the treatment group. Liver metastases were lower in adjuvant group than in the control group (8/68 versus 19/66). Toxicity was mild. Main toxic effects were thrombocytopenia, leukopenia, nausea and vomiting. A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed. In that particular case MMC was given after surgery. We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery, improves survival rate in gastric cancer resected patients.

Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers.

The aim of this study was to investigate the prognostic significance of a panel of biological parameters in patients with radically resected non-small cell lung cancers (NSCLC). 269 cases with pathological stage I-IIIA NSCLC were retrospectively analysed. Immunohistochemistry was performed to detect protein expression of p53, bcl-2, proliferating cell nuclear antigen (PCNA) and CD34. Polymerase chain reaction (PCR)/direct nucleotide sequencing method was used to detect mutations in K-ras (codons 12, 13, 61, exons 1-2). The Kaplan-Meier estimates of survival were calculated for clinical and biological variables using the Cox model for multivariate analysis. Histological subtype and the pathologic tumour extension (pT) were the most powerful clinical-pathological prognostic factors for survival (P=0.030 and P=0.031, respectively), whereas among the biological parameters, p53 overexpression (P=0.032) and K-ras mutation (P=0.078) had a negative prognostic role, as demonstrated by multivariate analysis. Conversely, bcl-2, PCNA and CD34 expression were not correlated with survival. Statistically significant associations between p53 expression and the squamous cell carcinoma (SCC) subtype, bcl-2 expression and SCC subtype, K-ras mutation and p53 negative expression, p53 and bcl-2, bcl-2 and PCNA overexpression were observed. In conclusion, some biological characteristics such as the K-ras and p53 status may provide useful prognostic information in resected NSCLC patients, in addition to the classical clinico-pathological parameters. However, further studies are needed to clarify the value of adopting biological prognostic factor into clinical practice.

Diminished anticoagulant and fibrinolytic activity following liver transplantation.

This study analyzed the coagulation changes in twenty patients after orthotopic liver transplantation. The procoagulant, anticoagulant, and fibrinolytic systems were studied during the first two postoperative weeks. Within the first postoperative day all extrinsic and intrinsic pathway factors became normal except factors IX, VII, and X, which recovered within the next 24 hr. Of interest are the changes in factor VIII, which reached a high concentration with an increase in its antigenic fraction during the study. However, coagulation inhibitors showed a different pattern. In fact, antithrombin III (AT-III) and protein C (PC) needed from 7 to 14 days to reach normal values. Total protein S (TPS) and free protein S (FPS) did not recover until day 7, whereas heparin cofactor II (HC-II) remained at subnormal levels throughout the study. Thrombin-antithrombin III complex (TAT) values were strikingly elevated in the immediate postoperative period. Fibrinolysis parameters showed plasminogen (PL) levels in the normal range until day 4. Antiplasmin (AP) followed a curve parallel to that of plasminogen but its levels were higher during this observation period. Similarly the initial elevation in plasminogen activator inhibitor 1 endothelial type (PAI-1) levels remained high until days 4 and 7. In summary, it can be concluded that during the postoperative phase after OLT a hypercoagulable state is developed as a result of diminished anticoagulant and fibrinolytic activity. This coagulation might be a nontechnical factor contributing to the thrombotic vascular complications of some liver recipients.

Effectiveness of daily low-dose cotrimoxazole prophylaxis for Pneumocystis carinii pneumonia in liver transplantation--an open clinical trial.

Pneumocystis carinii pneumonia (PCP) is an important infection in the setting of liver transplantation. Without prophylactic measures, the incidence of PCP reached 30% in our first 10 liver transplant patients. All patients but one, who had concomitant invasive aspergillosis, recovered with intravenous cotrimoxazole. We therefore prospectively studied, in an open clinical trial, the efficacy and safety of prophylaxis with daily low-dose cotrimoxazole (480 mg) in 60 patients. The incidence of PCP dramatically decreased to 1.7% (P<.01). Treatment was well tolerated, and discontinuation of therapy was only necessary in two patients with leukopenia. Nevertheless, the number of episodes of leukopenia was similar in both groups. Cotrimoxazole prophylaxis was not associated with increased nephrotoxicity. An overall benefit in the incidence of bacterial infection was not observed. We conclude that daily low-dose cotrimoxazole is effective and safe for prevention of PCP after liver transplantations.

Importance of surveillance mycobacterial cultures after liver transplantation.

The routine use of isoniazid prophylaxis after liver transplantation is a controversial issue because the benefits must be weighed against the risk of hepatotoxicity. We decided not to institute isoniazid prophylaxis but to study the efficacy of a surveillance mycobacterial program. One hundred patients were included in the protocol. Sputum and urine samples were processed before transplantation and on days 15, 30, 60, 90, 12, 150, and 180 for acid-fast stain and culture. One case of tuberculosis was promptly identified and successfully treated. Cases of tuberculosis with negative surveillance cultures were not identified. Our approach indicates that surveillance mycobacterial cultures can permit rapid identification of tuberculosis after liver transplantation and it is an alternative for groups who questioned isoniazid prophylaxis.

Investigation of HLA class I downregulation in breast cancer by RT-PCR.

Downregulation of HLA class I antigen expression has been reported in a significant proportion of primary breast carcinomas suggesting an escape mechanism from CTL mediated lysis leading to tumor dissemination and metastasis. We have previously reported the biochemical and immunohistochemical analysis of HLA total class I (W6/32 mAb), alpha-chain (Q1/28,TP25.99 mAbs) and beta(2)-microglobulin (Namb-1 mAb) subunits expression in 25 primary breast carcinomas. This study at protein level resulted in the observation of three different HLA class I expression patterns by both techniques: high, low, and absent downregulation patterns. To better characterize the HLA class I antigens downregulation we extended such analysis also at RNA level by RT-PCR using HLA-A, HLA-B, HLA-C, and beta(2)-microglobulin specific primers either in breast cancer or normal tissues derived from the same patient. None (100%) of the alpha-chain genes analyzed in patient tumor tissues showed significant reduction of expression. In 10 patients out of 25 (40%) the beta(2)-microglobulin gene showed complete loss of expression compared with the corresponding normal tissue counterpart, which showed a constitutive expression, whereas in 2 patients (12.5%) its expression was comparable with the normal counterpart. Sequence analysis at genomic level revealed no defects affecting beta(2)-microglobulin gene in those patients showing lack of expression. Also TAP1 and TAP2 genes expression were investigated in order to confirm or exclude involvement of the MHC class I molecules assembling machinery. The RT-PCR approach mainly confirmed our beta(2)-microglobulin biochemical analysis indicating that in breast cancer specimens it is possible to address the HLA class I gene downregulation as a phenomenon occurring at post-transcriptional level mainly affecting the beta(2)-microglobulin gene expression.

Analysis of HLA DP, DQ, and DR alleles in adult Italian rheumatoid arthritis patients.

We analyzed the distribution of DRB1, DQA1, DQB1, and DPB1 allelic variants in 48 rheumatoid arthritis (RA) patients, compared with 109 Italian random controls, using PCR amplification and hybridization with specific oligonucleotides. We confirm the previously reported increase of DR4 specificity, in comparison with healthy Italian individuals. In particular, we find a statistically significant positive association of DRB1*0401 and DRB1*0404 alleles with RA. However, when we compare the DR4+ groups, none of the DRB1*04 alleles is increased in the RA group. By sequence analysis, performed on 10 patients, we demonstrate that the DRB1*04 genes of RA show no difference from the DRB1*04 sequences previously published. From the molecular analysis of the other DRB1 polymorphic variants, we find a trend of positive association of DRB1*0101 in DR4-negative patients versus DR4-negative healthy controls and, in the group of DR4-negative and/or DR1-negative patients, a similar increase of DRB1*06. Also, we observe in RA patients a statistically significant increase of DQA1*0301 and DQB1*0302 accompanied by a significant decrease of DQA1*0201, DQA1*0501 and DQB1*0201. Finally, from the analysis of DPB1 gene, it can be assessed that the distribution of DPB1 alleles does not differ significantly between RA patients and healthy controls.

Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and rheumatoid arthritis patients from the northeast of Italy: absence of sequence variability.

Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.

Analysis of K-ras, p53, bcl-2 and Rb expression in non-small cell lung cancer cell lines.

Six non-small cell lung cancer (NSCLC) cell lines (A-549, Ca-Lu-6, SK-Lu-1, Ca-Lu-1, SK-Mes-1 and LX-1) were studied to assess the presence of multiple concomitant alterations of different oncogenes (K-ras, bcl-2) and tumor suppressor genes (p53, Rb) in NSCLC. K-ras (exon 1) and p53 (exons 5-8) gene mutations were determined via a PCR-based-DGGE (Denaturing Gradient Gel Electro-phoresis) and by sequencing approach. Different mutations were found in the Ist exon of K-ras gene in 5 of 6 cell lines examined. Five of six cell lines contained K-ras mutations at codon 12 (A-549, SK-Lu-1, LX-1) or codon 13 (SK-Mes-1, Ca-Lu-1). In addition, 5 of 6 cell lines showed p53 mutations of exon 8 (SK-Mes-1, Ca-Lu-1 cod. 280; LX-1 cod. 273) or exon 6 (Ca-Lu-6 cod. 196; SK-Lu-1 cod. 193). In 4 of these cell lines, p53 protein nuclear expression was also confirmed with DO-7 mAb immunocytochemistry. Expression of cytoplasmic bcl-2 protein, by anti-bcl-2 mAb flow cytometric analysis, was found in A-549, Ca-Lu-1, SK-Lu-1, SK-Mes-1 cell lines. In contrast, RT-PCR analysis of Rb gene could not identify any change in the cell lines examined. In conclusion, most NSCLC cell lines tested displayed concomitant multiple oncogene/tumor suppressor gene alterations.

Surgery in Spain.

The Iberian Peninsula-the southwestern point of Europe, between the Mediterranean Sea and the Atlantic Ocean-was visited and settled in ancient times by a variety of peoples. Phoenicians, Carthaginians, Celts, Greeks, Romans, Visigoths, and Arabs all left their mark on the peninsula, and their cultures blended together to found, among other things, a rich tradition in medicine and surgery. During the Renaissance, the fluid exchange of technical skills and knowledge with the rest of Europe and the emergence of universities ensured the development of a high level of medical expertise. Today, surgery in Spain is at the forefront of innovations in the field.

Anorexia and the effect of internal biliary drainage on food intake in patients with obstructive jaundice.

BACKGROUND: Anorexia is a frequent finding in patients with biliary obstruction (BO). This study investigates the role of biochemical and hormonal factors in the pathogenesis of reduced food intake in BO and the effects of internal biliary drainage. STUDY DESIGN: Sixty-two patients with BO were prospectively investigated. Transaminases, amylase, cholecystokinin, secretin, bile acids, tumor necrosis factor-alpha, and endotoxin were determined at admission. Caloric intake was quantified by a controlled diet. In a subset of 27 patients, studies were repeated after internal biliary drainage. RESULTS: Sixty-six percent of patients had spontaneous food intakes below the estimated caloric requirements. Serum bilirubin, alkaline phosphatase, and cholecystokinin plasma levels were independent predictor factors for calorie intake (p = 0.0001). After internal biliary drainage, cholestasis parameters and cholecystokinin concentrations decreased significantly; this was associated with an improvement of spontaneous food intake in both benign and malignant biliary obstruction (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Decreased food intake in BO was associated with the degree of obstruction and with increased cholecystokinin plasma levels. Biliary drainage improved biochemical and food intake derangements.

Nutritional aspects in oesophageal carcinogenesis (review).

The role of diet in carcinogenesis has received much attention in recent years. The incidence of oesophageal cancer varies widely in different geographical regions and oesophageal cancer shows one of the greatest correlations between the diet type and eventual malignant development. Oesophageal carcinogenesis involves the combined action of predispositional, initiatory, and promotional factors. Specific dietary deficiencies (vitamins and minerals) may create a sensitized "environment" for the combined activities of initiatory and promotional factors. Other predispositional factors include physical abrasion (irritant vegetal components, thermal injury) and chemical injuries (alcohol, tobacco). Initiatory factors such as nitrosamines or their precursors in the diet are also considered.

Sclerosing cholangitis after surgical treatment of hepatic echinococcal cysts. Report of three cases.

Three patients with sclerosing cholangitis after surgical treatment of echinococcosis of the liver are described. Before surgery, they had clinical symptoms that suggested a communication between the cyst and the biliary tract and, in two of them, the communication was later demonstrated by cholangiography. In each case, the cyst was injected with formalin solution. Soon after operation chronic cholestasis developed, with operative, cholangiographic, and histologic data suggesting sclerosing cholangitis. The role of formalin in the pathogenesis of this condition is discussed herein.

Scintisplenoportography in assessing patency of distal splenorenal shunts.

Scintisplenoportography was performed on 33 occasions in 28 cirrhotic patients who had bled from esophagogastric varices. In 17 cases scintisplenoportography was carried out after a retroperitoneal distal splenorenal shunt procedure and in the remaining 16 instances in patients without any surgical shunt. In four patients scintisplenoportography was performed before and after a surgical shunt procedure, and in one case, before and after the shunt thrombosed. Gammagraphic patterns and spleen-heart times helped determine which patients did not have a surgical shunt, which had a patent shunt, and which patients had a thrombosed shunt. A patent shunt pattern and a thrombosed shunt pattern have been defined. It is concluded that scintisplenoportography is a useful, reproducible, and safe method to assess the patency of distal splenorenal shunts.

Evaluation of palpable breast masses with 201Tl scintigraphy.

39 female patients (age range: 31-84 years) with palpable breast masses detected by physical examination, underwent 201Tl scintigraphy in order to assess its value in the detection of breast carcinomas and to differentiate them from benign breast masses. Planar images were carried out at 20-30 min and 2-3 h after intravenous administration of 111-185 MBq (3-5 mCi) of 201Tl chloride. In 12 patients single photon emission tomography (SPET) studies were also performed. In 18 patients the scintigraphic studies were positive and in 17 of these cases, breast carcinomas were confirmed. Tumour sizes ranged from 1.3 to 6 cm in diameter. In the remaining patient a false positive result was obtained where there was benign breast change. In three of seven cases, malignant axillary nodes were also detected. All 21 patients with negative scintigraphy had benign breast lesions. There were no differences between images obtained at 20-30 min and 2-3 h or between planar images and SPET studies. In 10 patients there was disagreement between mammography and 201Tl scans. 201Tl scans confirmed the presence of carcinoma in three cases and discarded malignancy in the other six cases. In the remaining case, 201Tl scan was false positive. 201Tl scintigraphy is useful in distinguishing malignant from benign breast masses, even when compared with mammography.

Pharmacological reactivity of granulation tissue.

The contractile system of the myofibroblast has well defined characteristics. The findings suggest the presence of 5-hydroxytryptaminergic as well as alpha and beta-adreno-receptors, although both appear to be immature. It does not have cholinergic or histaminergic receptors. The contractile system is inhibited by cytochalasin B and is not sensitive to colchicine. The contractile machinery is suggested to be the microfilament system, as it occurs in the contractile apparatus of primitive cells. This is in accordance with the role of myofibroblasts in granulation tissue neoformation.

The modified distal splenorenal shunt in the elective treatment of variceal hemorrhage.

We report on our experience with a modified version of the distal splenorenal shunt (DSRS) initially described by Warren. Since 1976 more than 150 shunts have been done in the department. The first part of this study shows the long-term results of a series of 100 consecutive patients treated electively. The estimated survival at 80 months was around 30%. On the other hand, the median survival rate (68 months) and the five-year survival (52%) of Child's A patients differed significantly from those of Child's B patients (8 months and 15%, respectively). These results suggested that the modified DSRS was an effective and relatively safe procedure for the elective treatment of variceal bleeding and warranted a prospective and randomized trial to compare DSRS and endoscopic sclerotherapy (ES). In the second part of the study, in which ES was compared with DSRS, both modalities showed a similar survival rate, although patients in the DSRS group had a higher incidence of encephalopathy and patients in the ES group were more prone to rebleed. It was concluded that ES was a good alternative to DSRS for the elective treatment of esophageal variceal bleeding. If orthotopic liver transplant is considered the only definitive mode of treatment for the elective management of portal hypertension, the DSRS should be reserved for patients in whom ES has not been totally effective, or varices are located predominantly in the fundus of the stomach.