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Adrian Reuben

Publications and source records attributed to Adrian Reuben.

36 records · Page 2Linked to original sources

Prospective evaluation of a 3.1-mm battery-powered esophagoscope in screening for esophageal varices in cirrhotic patients.

OBJECTIVE: Standard esophagogastroduodenoscopy (EGD) is costly and uses conscious sedation that cirrhotic patients may tolerate poorly. This study aimed to determine the feasibility and acceptance of unsedated esophagoscopy with an ultrathin battery-powered endoscope (BPE) in cirrhotic patients for diagnosing esophageal varices (EV). METHODS: We first studied the prevalence of significant gastroduodenal pathology that could be missed if only esophagoscopy were performed in cirrhotic patients undergoing liver transplant evaluation. A prospective study was then done to evaluate a BPE in EV screening. Unsedated per-oral endoscopy was first done by a single endoscopist using a BPE, followed by EGD by a second endoscopist who was masked to the BPE result. A visual analog score was used to determine patient tolerance. Patients were asked about their preference for endoscopy in the future. A paired Student t test and the kappa statistic were used in the statistical analysis. RESULTS: In the retrospective study, 199 patients were reviewed; three patients (1.5%) had gastric ulcers, and two patients (1%) had duodenal ulcers. In the prospective study, 28 cirrhotic patients (16 women) were evaluated. EV were diagnosed in 14 patients with a BPE, and 13 were confirmed by standard EGD (sensitivity and negative predictive value 100%, specificity and positive predictive value 93%, kappa = 0.93). EV were graded as large in one and small in 13 patients with a BPE, but small varices diagnosed in one patient were not confirmed on EGD. Both procedures were well tolerated by all patients. Twenty-seven of 28 patients preferred unsedated endoscopy with a BPE over EGD. CONCLUSIONS: Unsedated endoscopy with a BPE is safe and well tolerated. The diagnostic accuracy of a BPE for diagnosing EV is the same as by EGD. Esophagoscopy with a BPE is a potential alternative to EGD for EV screening.

Adolescent↗

The thin red line.

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Gastroenterology↗

Oncostatin M stimulates tissue inhibitor of metalloproteinase-1 via a MEK-sensitive mechanism in human myofibroblasts.

BACKGROUND/AIMS: We previously showed that in cultured human myofibroblasts (hMFBs), Oncostatin M (OSM)-stimulated collagen accumulation is associated with increased tissue inhibitor of metalloproteinase (TIMP)1 message. However, the mechanism is unknown. METHODS: hMFBs were isolated by outgrowth from cirrhotic liver explants and cultured. Using OSM (10 ng/ml) stimulation, with and without PD98059 (PD, a specific mitogen-activated protein kinase/extracellular signal-related kinase (MEK) inhibitor), we measured: TIMP-1 protein in culture medium by Western blot, TIMP-1 mRNA levels and stability by Northern analysis, TIMP-1 promoter activity (including transcription site mutation analysis), DNA binding activity to nuclear proteins by electrophoretic mobility shift assay (EMSA), and total and phosphorylated MAP kinase in hMFB extracts by Western blot. RESULTS: OSM stimulation of hMFBs increased TIMP-1 protein production 1.69-fold, TIMP-1 mRNA levels 2.36-fold, promoter activity 2.22-fold, TIMP-1 message stability, and phosphorylation of mitogen-activated protein kinase (MAPK). PD inhibited OSM-mediated stimulation of TIMP-1 protein, mRNA, promoter activity, phosphorylation of MAPK, and TIMP-1 message stability. An SP-1 transcription site of the TIMP-1 promoter is essential for OSM induction of TIMP-1 promoter activity. EMSA demonstrates that this site binds to transcriptional factors SP-1 and SP-3. CONCLUSIONS: OSM stimulates the TIMP-1 axis in hMFBs in vitro via a MEK-MAP kinase cascade.

Cells, Cultured↗

Reversal of activation of human myofibroblast-like cells by culture on a basement membrane-like substrate.

BACKGROUND: Liver injury transforms hepatic stellate cells into myofibroblast (MFB)-like cells. With recovery from injury, MFBs undergo apoptosis, but it is unknown whether they can also revert to quiescence. AIM: To determine whether human (h)MFBs become quiescent if cultured on a basement membrane-like substrate (Matrigel). METHODS: hMFBs obtained from cirrhotic liver were re-cultured on plastic or Matrigel. Expression of genes of collagen metabolism was assayed before and after transforming growth factor beta (TGFbeta) and Oncostatin M (OSM) stimulation. RESULTS: hMFBs had typical MFB-like morphology, with abundant alpha-smooth muscle actin (SMA) but no cytoplasmic lipid droplets. hMFBs re-cultured on Matrigel reverted to alphaSMA-negative, lipid droplet-positive quiescent morphology. alphaSMA, collagen alpha1(1) (COL1A1) and collagen alpha2(1) (COL1A2) messages were upregulated in hMFBs cultured on plastic, but suppressed by Matrigel. The opposite was true for metalloproteinase-1 mRNA. OSM but not TGFbeta reduced alphaSMA mRNA by 30% while TGFbeta but not OSM upregulated COL1A1 mRNA by 48%, in hMFBs on plastic. TGFbeta and OSM stimulated COL1A1 gene expression in Matrigel by 50 and 60%, respectively. CONCLUSIONS: Matrigel culture de-activates hMFBs yet collagen gene expression still responds to fibrogenic cytokines. The responses of hMFB gene expression to TGFbeta and OSM, are regulated differently by the extracellular matrix.

Actins↗

Child comes of age.

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History, 20th Century↗

Ito becomes a star.

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Gastroenterology↗

Prediction of esophageal varices in patients with cirrhosis.

GOALS: To identify predictors of esophageal varices (EV) using available clinical, laboratory, and diagnostic imaging variables. BACKGROUND: Patients with cirrhosis frequently undergo screening endoscopy for varices so that prophylactic therapy and/or follow up can be planned. It is unclear how often patients should be screened endoscopically for varices, and there are few data on the relationship of varices to nonendoscopic variables. STUDY: Charts were reviewed for 247 consecutive patients with cirrhosis who underwent screening esophagogastroduodenoscopy for varices. RESULTS: A total of 184 patients (68 women) were studied. Ninety-four patients (51%) had varices; of whom, 90 had only EV (small, n = 66; large, n = 24), 13 had EV and gastric varices, and 4 had isolated gastric varices. The distribution of EV according to the Child-Turcotte-Pugh class was as follows: A, 35%; B, 60%; and C, 69%, with roughly equal prevalence of large varices (29%, 24%, and 24%, respectively) in each class. Independent predictors of large varices were thrombocytopenia ( p = 0.02) and splenomegaly ( p = 0.04) seen using imaging. A platelet count of less than 68,000/mm 3 had the highest discriminative value for large EV with a sensitivity of 71% and a specificity of 73%. Splenomegaly had sensitivity and specificity of 75% and 58%, respectively. Using these two variables, we placed patients into one of four groups, with a risk for large varices ranging from 4% to 34%. CONCLUSIONS: The prevalence of EV in cirrhosis increases with the severity of liver disease, as expected. Thrombocytopenia and splenomegaly are independent predictors of large EV in cirrhosis. Further prospective studies might result in a discriminating algorithm to predict which patients with cirrhosis would benefit from early or regular endoscopy to detect clinically significant varices.

Adult↗