Losartan-induced hepatic injury

Losartan, an angiotensin II receptor antagonist, is widely used for the treatment of hypertension. Clinical experience with this drug has demonstrated that it is safe. Losartan-induced hepatic toxicity is extremely rare. We report a case of severe hepatic toxicity and fibrosis caused by losartan use, and we review four previously reported cases. Drug-induced hepatic injury may be seen during the treatment of hypertension by losartan and the clinician should be aware of this toxicity, especially during the initial phase of treatment.     

Effects of combined conventional and modified ultrafiltration in adult patients

BACKGROUND: Modified ultrafiltration (MUF) improves hemodynamics and postoperative recovery in children. Ultrafiltration (UF) may have similar benefits in adults. The purpose of this study was to investigate the effects of UF in adult patients. METHODS: A total of 40 adult patients undergoing cardiac surgery were randomized into a study group of conventional UF during bypass + venovenous MUF after bypass and a control group with no UF. Perioperative clinical variables, cytokines, and endothelin-1 levels were compared between groups. RESULTS: There was no mortality in either group. The patients in the study group had a greater rise in hematocrit (5.7% +/- 2.4% vs 1.2% +/- 1.9%, p < 0.001), hemoglobin (1.7 +/- 0.8 mg/mL vs 0.5 +/- 0.6 mg/mL, p < 0.0005), and platelet levels (27,800 +/- 29,200 vs -9,000 +/- 30,970, p < 0.001). Mean arterial blood pressure and CI increased after MUF (from 64.2 +/- 16.9 mm Hg to 72.3 +/- 14.1 mm Hg, p = 0.05, and from 2.4 +/- 0.7 to 2.8 +/- 0.6, p < 0.03, respectively). Postoperative oxygenation was better in the study group (alveolo-arterial PO2 tension gradient 74.6 +/- 43.9 mm Hg vs 107.2 +/- 27.8 mm Hg, p = 0.03). Ultrafiltration reduced postoperative bleeding (522.2 +/- 233.4 mL vs 740 +/- 198.4 mL, p < 0.003). CONCLUSIONS: A combination of conventional and modified UF is effective and safe in adult patients undergoing cardiac surgery. Ultrafiltration improved hemodynamics, hemostatic, and pulmonary functions. We recommend the use of combined UF in high-risk adult patients.     

In situ quantitative estimates of the age-related and diabetes-related changes in cerebral endothelial barrier antigen

To determine whether aging or diabetes, conditions known to alter the blood-brain barrier (BBB) is associated with changes in endothelial barrier antigen (EBA), a rat BBB-specific protein, in situ quantitation of forty vibrotome sections of cerebral tissue of 5 young (4 months old), 5 aged (26 months old) and 5 streptozotocin-induced diabetic rats after 4 weeks of diabetes were studied using immunohistologic techniques. The anti-EBA-stained microvessels were normalized against the total microvessels identified with either anti-EBA binding or anti-Glut-1 binding. The results indicate that the EBA-stained microvessels of the hippocampus, but not of other cerebral cortical areas or white matter, are reduced in aged rats(88.02±2.19%vs.80.65±2.44%, P < 0.01). There were no significant changes in the diabetic rats. These results support the notion that changes in the BBB correlate with the aging of the central nervous system.     

Outcome of partial hepatectomy for large (> 10 cm) hepatocellular carcinoma

BACKGROUND: Surgical resection for large (> 10 cm) hepatocellular carcinoma (HCC) is believed by many to be ineffective. The objective of the current study was to review the outcome of partial hepatectomy in patients with large HCC. METHODS: Between 1985 and 2002, 193 consecutive patients who underwent partial hepatectomy for HCC were identified from a prospective database. The 82 patients with tumors > 10 cm were compared with the remaining 111 patients with < or = 10 cm tumors. Clinicopathologic features were analyzed and prognostic factors were evaluated by univariate and multivariate analysis. RESULTS: The 5-year overall survival for patients with large HCC was 33% with a median of 32 months. Patients with < or = 10 cm tumors had similar survival. Furthermore, there was no significant difference between the groups in operative mortality (2% in large HCC vs. 6%) or recurrence rate. In patients with large HCC, vascular invasion by tumor and intraoperative blood loss > 2 liters predicted overall survival on multivariate analysis. CONCLUSIONS: Partial hepatectomy is safe for patients with large HCC. In selected patients with large tumors, resection achieves similar overall survival and recurrence-free survival to that of patients with smaller tumors. Minimizing intraoperative blood loss appears to be critical for favorable long-term outcome in patients with large HCC.     

Trefoil factor expression in biliary epithelium of graft-versus-host disease of the liver after allogeneic hematopoietic cell transplantation

BACKGROUND: The aims of this study were to determine the presence of trefoil factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic cell transplantation, to compare such expression in chronic liver diseases (CLD) with/without predominantly biliary disease, and to assess the effect of bile duct injury on the degree of TFF3 expression in BECs of cGVHD. METHODS: A total of 82 paraffin-embedded liver biopsy samples were reviewed. These samples were basically divided into two distinct groups according to the presence of ductal injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9 primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for the detection of TFF3 mRNA expression. RESULTS: Positive TFF3 immunohistochemical staining and the presence of TFF3 messenger RNA gene expression was demonstrably higher in group 1 than that in group 2 (P<0.0001 and P<0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P>0.05). The extent of TFF3 expression in GVHD samples with severe ductal injury were significantly more common than that of GVHD samples with mild/moderate ductal injury (P<0.0001). CONCLUSIONS: The expression of TFF3 in cGVHD of the liver is increased in response to bile duct damage and repair. Such expression seems to be related the severity of ductal injury.     

Is detection of asymptomatic recurrence after curative resection associated with improved survival in patients with gastric cancer?

BACKGROUND: It is not clear if more intense surveillance is associated with improved survival after curative resection for cancer. In the context of a followup program after curative gastrectomy, recurrence and survival were investigated for patients presenting with either symptomatic or asymptomatic recurrence. STUDY DESIGN: A prospectively maintained gastric cancer database was used to identify all patients who underwent a curative (R0) gastrectomy from July 1985 to June 2000. Survival curves were generated for patients with either symptomatic or asymptomatic recurrence, and the prognostic variables associated with outcomes were identified. RESULTS: Of 1,172 patients who underwent a curative (R0) gastrectomy, 561 patients (48%) had documented recurrence and 382 patients had complete data about symptoms. Median time to recurrence was 10.8months for asymptomatic patients and 12.4months for symptomatic patients (p = NS). Median postrecurrence survival was 13.5months for asymptomatic patients and 4.8months for symptomatic patients (p < 0.01). Median disease-specific survival was 29.4months for asymptomatic patients and 21.6months for symptomatic patients (p < 0.05). Variables predictive of poor postrecurrence survival included symptomatic recurrence, advanced stage (III/IV), poor differentiation, short disease-free interval (<12months), and multiple sites of recurrence. CONCLUSIONS: Followup did not identify asymptomatic recurrence earlier than symptomatic recurrence. Patients with symptomatic recurrence have more aggressive disease with a shorter postrecurrence survival. The impact of detecting asymptomatic recurrence in the course of followup after curative gastrectomy could not be distinguished from the effects of four powerful biologic variables that also interact to govern outcomes.     

The use of a combined technique in reduction mammaplasty (inferior pyramidal and superior glandular techniques)

The management of mammary hypertrophy is a developing process. The common surgical options for reduction mammaplasty include amputation with free nipple graft as well as the bipedicled, inferior pedicle and vertical pedicle techniques. All techniques are used widely. Disadvantages of these procedures include nipple areola necrosis, insensitivity, hypopigmentation, and poor breast projection. Even with the standard modifications of the original techniques, the resultant breast and nipple may be wide and flat. The purpose of this study was to assess whether combined inferior pyramidal pedicle and superior glandular pedicle reduction mammaplasty can optimize nipple and breast projection. Attention will focus on the viability and sensation of the nipple areola complex. Nine patients with mammary hypertrophy were studied. The change in nipple position ranged from 7 to 13 cm. The amount of tissue removed from each breast ranged from 500 to 1150 g. Nipple/areola sensation was retained in all cases with the exception of one breast. Nipple/areola necrosis or hypopigmentation were not observed. Optimal central breast projection was maintained in all patients, and postoperative evaluation was carried out at 12 and 22 months. The patient satisfaction was very high.     

Mitral annular calcification and brown tumor of the rib in a child with chronic renal failure

Mitral annular calcification and liquefaction necrosis of this lesion mimicking intracardiac tumor because of secondary hyperparathyriodism have been described in adult patients with chronic renal failure, but have not been reported in children. Chronic renal failure is one of the predisposing factors of this condition. We report the case of a 13-year-old patient with continuous ambulatory peritoneal dialysis with severe hyperparathyroidism who was found to have intracardiac and rib lesions considered to be brown tumors.