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Biomedical subjects

Kevin D Mullen

Publications and source records attributed to Kevin D Mullen.

27 records · Page 2Linked to original sources
PubMed2003

Newer aspects of hepatic encephalopathy.

Recently attempts have been made to standardize terminology in the field of hepatic encephalopathy. We are now facing a new problem. Chronic hepatitis C-induced cirrhosis occurs in an older population; this may change the presentation pattern of hepatic encephalopathy in future. Ammonia has once again become prominent as the leading toxin likely to play a role in the pathogenesis of this syndrome. How ammonia interacts with other proposed mechanisms should be an area of active research. The treatment arena has seen some advances. Unfortunately, the economics of having newer treatments approved in the USA is formidable. Rifaximine, L-ornithine-L-aspartate, sodium benzoate and possibly flumazenil appear to be significant advances. More elective shunt suppression for selected patients will be seen. Liver transplantation remains the only option for truly intractable hepatic encephalopathy.

Ammonia↗
PubMed2003

Interplay of portal pressure, portal perfusion and hepatic arterial inflow in modulating expression of hepatic encephalopathy in patients with spontaneous or artificially created portosystemic shunts.

The major theme of this discussion is how portal pressure after portosystemic shunt procedures may modulate the expression of hepatic encephalopathy. Decades of emphasis on the paramount importance of maintaining portal venous perfusion after shunt procedures is now being re-examined. In countries where non-cirrhotic portal hypertension is common, physicians have long recognized that hepatic encephalopathy is rare even with total portosystemic shunting. However, once decompressive shunts are created, hepatic encephalopathy becomes a clinical problem. Why this occurs needs to be better understood. In the meantime, there has been virtual abandonment of surgical shunts in favor of endoscopic variceal ablation treatment. This is despite the fact that surgical shunts that only partially decompress the portal hypertension are associated with excellent long-term control of variceal bleeding and low rates of hepatic encephalopathy. The time has come to once again examine the key relationship between portal pressure, portal perfusion with hepatic arterial inflow in inducing hepatic encephalopathy after creation of portosystemic shunts.

Hepatic Encephalopathy↗
PubMed2002

Surprisingly small effect of antiviral treatment in patients with hepatitis C.

BACKGROUND: The effect and applicability of interferon-based antiviral therapies in the general population of persons with hepatitis C virus (HCV) infection are unknown. OBJECTIVE: To determine the applicability and usefulness of anti-viral therapy in a metropolitan clinic population. DESIGN: Retrospective case series of consecutively referred patients. SETTING: A teaching county hospital in Cleveland, Ohio. PATIENTS: 327 patients referred to a liver clinic after a positive result for antibody against HCV on enzyme-linked immunosorbent assay (ELISA). MEASUREMENTS: Treatment rates; reasons for nontreatment. RESULTS: 34 patients had no detectable HCV RNA. Of the remaining 293 patients, 72% were not treated for the following reasons: 37% did not adhere to evaluation procedures, 34% had medical or psychiatric contraindications, 13% had ongoing substance or alcohol abuse, 11% preferred no treatment, and 5% had normal liver enzyme levels. Only 83 patients (28%) were treated; 13% had a sustained viral response. CONCLUSION: Most patients with HCV infection are not candidates for interferon-based therapies; alternative interventions should be sought for these patients.

Antiviral Agents↗
PubMed2002

The liver in other (nondiabetic) endocrine disorders.

The liver has a major role in the proper maintenance of intermediate metabolism and endocrine homeostasis. It contains enzymes that are essential for hormonal biotransformation and the regulation of numerous metabolic reactions, which control hormone metabolism. The liver also manufactures several proteins, which carry circulating hormones to their effector sites. The endocrine system exerts tight control of the metabolic reactions within the liver, which also can be disturbed by endocrine disorders. These types of interactions and the effects of the exogenous hormones and the drugs that are used as treatment for hormonal disorders are discussed.

Cushing Syndrome↗
PubMed2002

Preservation of portal pressure improves growth and metabolic profile in the male portacaval-shunted rat.

The portacaval anastomosis (PCA) rat model and human cirrhosis have many metabolic and nutritional abnormalities in common, such as growth retardation, hepatic and gonadal atrophy, and hyperammonemia. The severity of these abnormalities is variable and may be related to a number of factors, including portal pressure, portosystemic shunting, dietary intake, and how efficiently food is used. Therefore, this rat model was used to study these variables with the intent of gaining insights for improving the management of portal hypertension and malnutrition in human cirrhosis. A nonsuture end-to-side PCA (N = 100) or sham surgery (N = 71) was performed in 100 male rats. Four weeks after surgery, body and organ weights, food intake, serum ammonia, and serum amino acids were measured at death. In a subgroup of rats, (sham 7; PCA 34) portal venous pressure, degree of portosystemic shunting, and organ and body weights were obtained at death. Growth, liver weight, and testes weight were decreased, ammonia levels were higher, and the ratios of branched chain to aromatic amino acid (BCAA/AAA) were lower in the PCA group compared to the sham animals (P < 0.05). Since spleen weights correlated with portal pressure (P = 0.01), the PCA animals were then divided into those with preserved and those with low portal pressures based on spleen weight. The PCA group with preserved portal pressure had better growth, larger livers and testes, lower serum ammonia, and higher BCAA/AAA levels than the PCA group with low portal pressure; improvements associated with normal amounts of food intake and better food efficiency than the low pressure animals (P < 0.05 or better). Sham animals had no portosystemic shunting, while 100% shunting occurred in both PCA groups regardless of the portal pressure. In conclusion, preservation of portal pressure after portacaval anastomosis provides metabolic and nutritional benefits, which are independent of portosystemic shunting and associated with normal dietary intake and better preserved food efficiency.

Amino Acids, Aromatic↗
PubMed2002

The utility of radiological imaging in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: This prospective study evaluates the role of radiological modalities in establishing the diagnosis of nonalcoholic steatohepatitis (NASH). METHODS: Consecutive patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were enrolled (2000-2001). Patients with other liver diseases and significant alcohol consumption (>20 g/day) were excluded. Clinicodemographic data were gathered at the time of liver biopsy. Each biopsy specimen was assessed by a hepatopathologist. Each patient underwent a limited abdominal ultrasonography (US), computerized tomography (CT), and magnetic resonance imaging (MRI). Films were interpreted by a radiologist who used a predetermined radiological protocol. Each radiological study was reread by the same radiologist and a second radiologist. RESULTS: Patients with NASH had greater aspartate aminotransferase levels (P = 0.03), greater ferritin levels (P = 0.05), more hepatocyte ballooning (P < 0.0001), and more fibrosis (P = 0.002). None of the radiological features distinguished between NASH and other types of NAFLD. No radiological modality detected the presence of hepatocyte ballooning, Mallory's hyaline, or fibrosis, which are important features in the diagnosis of NASH. The presence of >33% fat on liver biopsy was optimal for detecting steatosis on radiological imaging. CONCLUSIONS: Differences between NASH and nonprogressive NAFLD were not apparent with any radiological modality. Of the pathologic features important for establishing the diagnosis of NASH, only the severity of steatosis was reflected in these radiological modalities. Good intraobserver agreement was evident for each modality (US, CT, and MRI) that was superior to interobserver agreement.

Adult↗
PubMedDate not supplied

Triple combination of interferon alpha-2b, ribavirin, and amantadine for treatment of chronic hepatitis C.

Retreatment of interferon-resistant chronic hepatitis C represents a significant clinical challenge. In an open-label, pilot study, the safety and efficacy of interferon alpha-2b, ribavirin, and amantadine were assessed. Twenty patients with chronic hepatitis C who had previously failed to respond to a course of interferon monotherapy followed by a course of combination therapy (10 patients received interferon alpha-2b [3 million units three times a week] plus ribavirin [800 mg/d] and 10 patients received interferon alpha-2b [3 million units three times a week] plus amantadine [200 mg/d]) were enrolled in this retreatment protocol. One month after discontinuation of their last regimen, patients started treatment with interferon alpha-2b (3 million units three times a week), ribavirin (1,000-1,200 mg/d), and amantadine (200 mg/d). Biochemical and virologic end points were monitored. Patients with hepatitis C virus (HCV) RNA levels of <100 copies/mL at the end of 24 weeks of therapy completed a 48-week course of interferon alpha-2b, ribavirin, and amantadine treatment. Of the enrolled subjects, 60% were male, 85% were white, 85% had HCV genotype 1, and 20% had histologic cirrhosis. The mean age +/- SD of the patients was 44.1 +/- 4.9 years, the mean baseline HCV RNA level +/- SD was 1,845,150 +/- 1,279,069 copies/mL, and the mean baseline alanine aminotransferase level +/- SD was 130 +/- 100 U/L. Five patients (25%) became HCV RNA negative (<100 copies/mL) after 24 weeks of treatment, with only three patients (15%) remaining HCV RNA negative at the end of 48 weeks of treatment. This end of treatment response was sustained 6 months after the discontinuation of treatment in only two patients (10%). In this interferon-resistant group, a treatment regimen of interferon alpha-2b, ribavirin, and amantadine was associated with only a 10% sustained viral eradication rate.

Adult↗