Activity and responsiveness of the renin-angiotensin system in the aging rat.

The systemic renin-angiotensin system (RAS) is suppressed in normal aging, but the activity of the tissue RAS is not well defined. We examined the systemic and intrarenal RAS status of aging normal rats and responses to suppression and stimulation of the production of endogenous ANG II. Studies were performed in young (3 mo) and early aging (15 mo) male Sprague-Dawley rats.

MAPK signaling and the kidney.

Following an overview of the biochemistry of mitogen-activated protein kinase (MAPK) pathways, the relevance of these signaling events to specific models of renal cell function and pathophysiology, both in vitro and in vivo, will be emphasized. In in vitro model systems, events activating the principal MAPK families [extracellular signal-regulated and c-Jun NH(2)-terminal kinase and p38] have been best characterized in mesangial and tubular epithelial cell culture systems and include peptide mitogens, cytokines, lipid mediators, and physical stressors. Several in vivo models of proliferative or toxic renal injury are also associated with aberrant MAPK regulation.

Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes.

Nitric oxide (NO) has been implicated in the pathogenesis of renal hemodynamic changes in diabetes mellitus. However, the contribution of nitric oxide synthase (NOS) isoforms to intrarenal production of NO in diabetes remains unknown. To explore the role of NOS1 in the control of renal hemodynamics in diabetes, we assessed renal responses to inhibition of NOS1 with S-methyl-L-thiocitrulline (SMTC; administered into the abdominal aorta) in moderately hyperglycemic streptozotocin-diabetic rats (D) and their nondiabetic (C) and normoglycemic diabetic counterparts.

Association of fungal infection and increased mortality in liver transplant recipients.

Background: Invasive fungal infection is associated with increased morbidity and mortality following orthotopic liver transplantation (OLTx). Understanding the risk factors associated with fungal infection may facilitate identification of high-risk patients and guide appropriate initiation of antifungal therapy.

Objectives: The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in OLTx recipients.

Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor.

STI 571 (formerly known as CGP 57148B) is a known inhibitor of the c-abl, bcr-abl, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases. This compound is being evaluated in clinical trials for the treatment of chronic myelogenous leukemia. We sought to extend the activity profile of STI 571 by testing its ability to inhibit the tyrosine kinase activity of c-kit, a receptor structurally similar to PDGFR.

Posttranscriptional cell cycle-dependent regulation of human FANCC expression.

The Fanconi Anemia (FA) Group C complementation group gene (FANCC) encodes a protein, FANCC, with a predicted M(r) of 63,000 daltons. FANCC is found in both the cytoplasmic and the nuclear compartments and interacts with certain other FA complementation group proteins as well as with non-FA proteins. Despite intensive investigation, the biologic roles of FANCC and of the other cloned FA gene products (FANCA and FANCG) remain unknown.

Axillary artery anastomosis to avoid axillofemoral bypass disruption.

Acute disruption at or adjacent to axillary anastomoses of axillofemoral grafts has been sporadically reported. The cause of this serious complication is believed to be attributable to mechanical stresses on the proximal portion of the graft and anastomosis. A modification in the proximal tunneling of the axillofemoral graft, which appears to have effectively reduced the occurrence of this vexing complication, is described in this report.

Improved prediction of nonepileptic seizures with combined MMPI and EEG measures.

Purpose: Nonepileptic seizures (NESs) are frequently mistaken for epileptic seizures (ESs). Improved detection of patients with NESs could lead to more appropriate treatment and medical cost savings. Previous studies have shown the MMPI/MMPI-2 to be a useful predictor of NES.

Ras signaling in the inner medullary cell response to urea and NaCl.

The small guanine nucleotide-binding protein Ras, activated by peptide mitogens and other stimuli, regulates downstream signaling events to influence transcription. The role of Ras in solute signaling to gene regulation was investigated in the murine inner medullary collecting duct (mIMCD3) cell line. Urea treatment (100-200 mM), but not sham treatment, increased Ras activation 124% at 2 min; the effect of NaCl did not achieve statistical significance.

Is a single preoperative duplex scan sufficient for planning bilateral carotid endarterectomy?

Purpose: Duplex scanning is often the sole imaging study before carotid endarterectomy (CEA). Patients with bilateral severe internal carotid artery (ICA) stenosis may be considered for bilateral CEA. High-grade ICA stenosis, however, may artifactually elevate velocity measurements used to quantify stenosis in the contralateral ICA.

Fatal fulminant hepatitis associated with bromfenac use.

Objective: To report a case of fulminant hepatic failure associated with the use of bromfenac, a new analog of the phenyl acetate class of nonsteroidal antiinflammatory drugs.

Case Summary: A 60-year-old white woman with liver failure who had no known history of chronic liver disease was transferred to the liver transplant unit for evaluation. For three months preceding her illness, the patient was treated with bromfenac 25 mg po qid for arthritic pain.

Distant processing of pancreas islets for autotransplantation following total pancreatectomy.

Background: Small duct chronic pancreatitis is associated with intractable pain and failure to thrive, usually unresponsive to conventional management approaches. Total pancreatectomy is considered after failure of medical intervention. The major morbidity following total pancreatectomy is diabetes mellitus with its associated complications.

Vancomycin-resistant Enterococcus in liver transplant patients.

Background: Vancomycin-resistant Enterococcus (VRE) infection is emerging in the transplant population, and there is no effective antibiotic therapy available. The aims of this retrospective review were to (1) investigate the outcome of and (2) identify common characteristics associated with VRE infection and colonization in orthotopic liver transplant (OLTx) candidates.

Methods: From October 1994 through September 1998, 126 isolates of VRE were identified in 42 of 234 OLTx recipients and 5 OLTx candidates who did not proceed to transplantation.

Quantitative trait loci affecting peak bone mineral density in mice.

Peak bone mass is a major determinant of risk of osteoporotic fracture. Family and twin studies have found a strong genetic component to the determination of bone mineral density (BMD). However, BMD is a complex trait whose expression is confounded by environmental influences and polygenic inheritance.

Hypotonicity activates transcription through ERK-dependent and -independent pathways in renal cells.

Acute hypotonic shock (50% dilution of medium with sterile water, but not with isotonic NaCl) activated the extracellular signal response kinase (ERK) mitogen-activated protein (MAP) kinases in renal medullary cells, as measured by Western analysis with a phospho-ERK-specific antibody and by in vitro kinase assay of epitope-tagged ERKs immunoprecipitated from stable HA-ERK transfectants. Hypotonicity also activated the transcription factor and ERK substrate Elk-1 in a partially PD-98059-sensitive fashion, as assessed by chimeric reporter gene assay. Consistent with these data, hypotonic stress activated transcription of the immediate-early gene transcription factor Egr-1 in a partially PD-98059-sensitive fashion.

Liver transplantation for disulfiram-induced hepatic failure.

Fulminant hepatitis is a rare but potentially fatal adverse reaction that may occur after the use of disulfiram. A patient without a known history of liver disease was transplanted for fulminant hepatic failure secondary to disulfiram. A high index of suspicion and aggressive therapeutic approaches are essential for the prompt diagnosis and treatment of disulfiram-induced hepatic failure.

Timing and severity of initial hepatitis C recurrence as predictors of long-term liver allograft injury.

Background: The majority of patients infected with hepatitis C virus (HCV) undergoing liver transplantation develop evidence of histologic recurrence, and multiple mechanisms are likely poised to affect long-term allograft injury. The purpose of this analysis was to study the hypothesis that histologic and biochemical features at the onset of HCV recurrence predict the long-term evolution of allograft hepatitis.

Methods: We studied 34 consecutive liver transplant recipients with evidence of histologic HCV recurrence and with a minimal histologic follow-up of 1 year (up to 6.

Hepatic allograft abscess with hepatic arterial thrombosis.

Background: Intrahepatic abscess (IA) is an uncommon complication after liver transplantation (OLTx) usually found in the setting of hepatic arterial thrombosis (HAT) often with associated biliary tree necrosis and/or stricture. Conventional treatment of IA in this setting has required retransplantation.

Methods: A retrospective review of 274 patients (287 OLTx) from September 1991 through September 1996 was performed.

Biliary tract complications of side-to-side without T tube versus end-to-end with or without T tube choledochocholedochostomy in liver transplant recipients.

Background: Biliary anastomotic complications remain a major cause of morbidity in liver transplant recipients, ranging between 10% and 50% in large clinical series. An end-to-end choledochocholedochostomy with or without T tube (CDCD EE with T tube and CDCD EE w/o T tube) and a Roux-en Y choledochojejunostomy have been standard methods for biliary drainage.

Methods: The objectives of this retrospective study were to: (1) evaluate the incidence of biliary tract complications using a new method of side-to-side choledochocholedochostomy without T tube (CDCD SS w/o T tube) and (2) compare the results of CDCD SS w/o T tube with those of CDCD EE with T tube and CDCD EE w/o T tube.

Management of symptoms of gastroesophageal reflux disease: does endoscopy influence medical management?

Objectives: The purpose of this study was to examine the theories that underlie the clinical decision to perform endoscopy in patients with symptoms of gastroesophageal reflux disease (GERD). Physicians reported that they use endoscopic findings to modify medical treatment of GERD. This study was undertaken to test this hypothesis in clinical practice.

Cytomegalovirus viremia: risk factor for allograft cirrhosis after liver transplantation for hepatitis C.

Background: Despite recent advances in diagnosis and treatment, cytomegalovirus (CMV) infection continues to be a common cause of morbidity in liver transplant (LT) recipients. Because CMV infection suppresses cell-mediated immunity, which seems to be important in neutralizing hepatitis C virus (HCV) infection, we assessed the impact of CMV infection on histopathological HCV recurrence after LT.

Methods: The study group was comprised of 43 consecutive LT recipients with at least 6 months of histologic follow-up.

Risk factors for Barrett's esophagus in community-based practice. GORGE consortium. Gastroenterology Outcomes Research Group in Endoscopy.

Objectives: Endoscopy is often performed in patients with gastroesophageal reflux (GER) disease because of concern about the presence of Barrett's esophagus (BE). The purpose of this study was to determine whether the duration of GER symptoms and/or a history of esophagitis was associated with an increased risk of BE.

Methods: This was an observational, prospective, community-based study.

Urea inducibility of egr-1 in murine inner medullary collecting duct cells is mediated by the serum response element and adjacent Ets motifs.

The renal medullary solute urea increases transcription and protein expression of the zinc finger-containing transcription factor Egr-1 in a renal epithelial cell-specific fashion. Transient transfection of mIMCD3 cells with a luciferase reporter gene driven by 1.2 kilobases of the murine egr-1 5'-flanking sequence showed 4-fold increase in reporter gene activity with 200 mM urea treatment.