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Biomedical subjects

Kevin D Mullen

Publications and source records attributed to Kevin D Mullen.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of aromatase improves nutritional status following portacaval anastomosis in male rats.

BACKGROUND/AIMS: The portacaval anastamosis (PCA) rat is a model of the nutritional and endocrine consequences of liver cirrhosis. We hypothesized that failure to gain body weight in the PCA rat was the consequence of low testosterone levels and will be reversed by 4-hydroxyandrostenedione, a specific aromatase inhibitor. METHODS: Male Sprague-Dawley rats subjected to an end-to-side PCA or sham surgery were administered either 4-hydroxyandrostenedione or vehicle. Food intake, food efficiency, and body weight were measured, animals sacrificed 3 weeks after surgery, visceral organs harvested and plasma sex steroids measured. Hepatic RNA was extracted and dot blots done to quantify the expression of sex hormone dependent enzymes 16alpha hydroxylase and 15beta hydroxylase. RESULTS: Growth, food intake, food efficiency and plasma testosterone were lower and plasma estradiol higher in PCA than sham rats. Hepatic expression of testosterone driven 16alpha hydroxylase was lower and estradiol driven 15beta hydroxylase higher in PCA rats. These alterations were reversed by 4-hydroxyandrostenedione. CONCLUSIONS: These observations demonstrate that use of aromatase inhibitor reverses the nutritional and endocrine abnormalities in the PCA rat and suggest that this approach may be useful in cirrhotic patients.

Animals↗
PubMed2006

Improving compliance with postpolypectomy surveillance guidelines: an interventional study using a continuous quality improvement initiative.

BACKGROUND: Despite guidelines, physicians tend to perform postpolypectomy surveillance colonoscopies too frequently. OBJECTIVE: The objective of the study was to determine the baseline compliance rate with postpolypectomy guidelines in our unit and to determine the influence of a continuous quality improvement (CQI) intervention on improving the compliance rate and on decreasing the potential additional costs because of the scheduling of postpolypectomy surveillance colonoscopies earlier than indicated. DESIGN: This was a single-arm, pretest-posttest design. SETTING: This study took place at a tertiary care, academic medical center. PATIENTS: The medical records of all patients who underwent colonoscopy with polypectomy in our unit retrospectively during 6 months preceding (baseline period) and prospectively for 6 months after an intervention (postintervention period) were reviewed for patient demographics, colonoscopy findings, and scheduling of repeat colonoscopies. INTERVENTION: We used 3 components: (1) distribution of a wallet-size card with a summary of postpolypectomy guidelines to all endoscopists, (2) placement of guideline charts near computers used for typing endoscopy reports, and (3) distribution and reinforcement of the guidelines in a monthly continuous quality improvement meeting. MAIN OUTCOME MEASURES: The main outcome measures were compliance rates, mean times to repeat colonoscopy, and additional costs from surveillance colonoscopies being scheduled earlier than indicated were compared between the two periods. RESULTS: There were 278 patients in the baseline period and 242 in the postintervention period, with similar patient and polyp characteristics. After the intervention, the compliance rate with guidelines improved from 57.2% to 81% (p < 0.001). The mean time to a repeat colonoscopy increased from 4.5 to 5.2 years (p = 0.003) (i.e., a 14% reduction in the number of postpolypectomy surveillance colonoscopies performed per year). This would result in a reduction of a total of 73 surveillance colonoscopies per year in our unit, with a projected cost savings of 171,331 dollars per year (cost of a colonoscopy assumed at 2347 dollars). LIMITATIONS: The limitation of the study was possible enhanced performance secondary to being observed (Hawthorne effect). Because more than 1 intervention was used, we do not know which one is more effective. CONCLUSIONS: Relatively simple and easy-to-implement quality improvement initiatives can significantly enhance compliance with postpolypectomy guidelines and result in cost savings because of a reduction in the number of postpolypectomy surveillance colonoscopies being scheduled earlier than recommended guidelines.

Colonoscopy↗
PubMed2006

Afternoon colonoscopies have higher failure rates than morning colonoscopies.

BACKGROUND: There are several known predictors of an incomplete colonoscopy or difficult colonoscopy. In addition, inadequate bowel preparation has been reported in procedures scheduled later in the day. Operator fatigue, which tends to be higher as the day passes on, may also impact colonoscopy completion rate. AIMS: To determine the influence of performing outpatient colonoscopies in the afternoon versus morning on the completion rates of colonoscopy and adequacy of bowel preparation. METHODS: Retrospective chart review of all outpatient colonoscopies performed between November 2003 and October 2004 in the Division of Gastroenterology at MetroHealth Medical Center in Cleveland, Ohio. Patient demographics, indications for procedure, and colonoscopic findings were reviewed. Patients received polyethylene glycol electrolyte-based bowel preparation in the evening prior to the day of the scheduled colonoscopy. RESULTS: A total of 2,087 colonoscopies was performed, of which 1,084 were in the morning and 999 were in the afternoon. Patients in the morning and afternoon were similar in regards to the known risk factors predictive of an incomplete colonoscopy. The incompletion rate was significantly higher in the afternoon compared to the morning (6.5% vs 4.1%, P= 0.013, OR for incompletion was 1.64, CI 1.11-2.44). Inadequate bowel preparation was found in 167 out of 1,084 (15.4%) colonoscopies in the morning and 197 out of 999 (19.7%) colonoscopies in the afternoon (P= 0.011). Even after excluding incomplete colonoscopies due to poor bowel preparation precluding examination, the incompletion rate was still higher in the afternoon (5% vs 3.2%, P= 0.043, OR 1.60, CI 1.03-2.51). CONCLUSIONS: Scheduling of colonoscopies in the afternoon compared to the morning may be an independent predictor of an incomplete colonoscopy and inadequate bowel preparation. According to our study findings, scheduling of all outpatient colonoscopies preferentially in the morning would avoid suboptimal procedures in 5% of patients and the need for unnecessary repeat colonoscopy or an alternative imaging study in 2.4% of patients.

Aged↗
PubMed2005

Pegylated interferon alpha-2b, ribavirin and amantadine for chronic hepatitis C.

In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon alpha-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed. In this open-label pilot study, two separate patient populations with chronic hepatitis C and viremia were enrolled: treatment-naive and those who had failed a previous course of treatment. Patients were started on pegylated interferon alpha-2b at a dose of 1.5 microg/kg weekly with ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for 4 weeks, followed by pegylated interferon alpha-2b, 0.5 microg/kg weekly, ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for another 20 weeks. Patients with undetectable HCV RNA at week 24 continued this regimen for a total of 48 weeks and were followed for another 24 weeks. Patients with undetectable virus (<50 IU/mL) after 24 weeks of follow-up were considered to have SVR. Health-related quality of life and safety data were also collected. Sixty-nine treatment-naive and 99 nonresponder patients with chronic hepatitis C were enrolled in the study. Of all patients enrolled, 74% were male, aged 47.27+/-5.76 years; their body mass index (BMI) was 28.87+/-5.05 kg/m2, 79.4% were white, 85% had HCV genotypes 1 and 4, and 36% had cirrhosis. Their baseline HCV RNA was 689,242+/-698,030 IU/mL, with a baseline ALT of 107.25+/-79.08. Of the entire cohort, 35 (21%) discontinued early due to side effects or loss to follow-up. Significant anemia (hemoglobin, < 10 g/dL) occurred in 11% (19/168), while severe anemia (hemoglobin, <8.5 g/dL) occurred in 0.6% (1/168). In the treatment-naive group, sustained virologic response (SVR) was 34.3%, versus 19.4% for the group who had previously failed to respond to a course of treatment (P = 0.01). For both groups combined, virologic response after 24 weeks of therapy was 40.5%, with an end-of-treatment virologic response of 35.7% and a SVR of 26.2%. Patients with genotypes 1 and 4 had lower response rates than those with genotypes 2 and 3 (SVR, 21 vs. 46%; P = 0.001). Patients with advanced fibrosis (Metavir stages 3 and 4) tended to have lower response rates than those with minimal or mild fibrosis (Metavir stages 0-2) (SVR, 10 vs. 30%; P = 0.08). African-American patients with HCV had lower response rates than Caucasians or other ethnic groups (SVR, 4 vs. 29 vs. 20%; P = 0.04). Age, gender, and BMI did not affect SVR. The addition of amantadine to pegylated interferon alpha-2b and ribavirin does not seem to increase the efficicacy of this regimen.

Adult↗
PubMed2005

Long-term management of alcoholic liver disease.

Despite the epidemics of viral hepatitis C and nonalcoholic fatty liver disease, alcohol remains one of the major causes of liver disease. Commonly, hepatitis C and other liver diseases are found in association with alcohol consumption. This association in many instances is noted to accelerate the progression of liver disease. In many respects, the long-term management of alcoholic liver disease is not dissimilar from the long-term management of patients with cirrhosis from other etiologies. One major element is the abstinence of alcohol use. The ability to maintain sobriety has a major impact on the outcome of patients with alcoholic cirrhosis because maintaining abstinence can lead to significant regression of fibrosis and possibly early cirrhosis. Similarities in managing patients with cirrhosis due to alcohol or cirrhosis from other causes include vaccination to prevent superimposed viral hepatitis and screening for esophageal varices and hepatocellular carcinoma with subsequent appropriate therapy.

Adrenal Cortex Hormones↗
PubMed2004

MARS--does it stand the test of time?

Artificial liver support systems have been tested for decades in the management of liver failure. Generally, after some promising results published as case series, the device either disappears or fails to show significant benefit in controlled trials. Recently, the molecular absorbent recycling systems (MARS) or extracorporeal albumin dialysis (ECAD) technique appears to have broken this trend. Responding to the title one could summarize by saying this technique so far has stood the test of time. Data in support of its use in acute liver failure (ALF) is still scant and difficult to assess. However, in a well known but not very well defined entity of acute on chronic liver failure (AOCLF) the ECAD technique has been shown to improve survival compared to a similar randomized control group receiving standard supportive therapy. This well tolerated liver support system has real potential for widespread application if further well designed multicenter clinical trials continue to support its effectiveness. Its future lies probably in the management of the moribund hospitalized patient on the transplant list awaiting a donor liver.

Albumins↗
PubMed2004

Resolution of hereditary hemorrhagic telangiectasia and anemia with prolonged alpha-interferon therapy for chronic hepatitis C.

Hereditary hemorrhagic telangiectasia is a group of autosomal dominant disorders, characterized by telangiectases that develop in the skin, mucous membranes, and visceral organs. Currently, there is no satisfactory treatment of hereditary hemorrhagic telangiectasia. Interferon has never been used for the treatment of hereditary hemorrhagic telangiectasia. In this case, we report disappearance of hereditary hemorrhagic telangiectasia lesions after 12 months of treatment with interferon-alpha for chronic hepatitis C. Further studies are warranted to evaluate its role and potential use in the treatment of hereditary hemorrhagic telangiectasia.

Anemia↗
PubMed2004

Obesity and non-alcoholic fatty liver disease in chronic hepatitis C.

BACKGROUND: Superimposed non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) may affect HCV-related fibrosis. We performed a study to determine the relationship between NAFLD and chronic hepatitis C. METHODS: One hundred and twenty patients with chronic hepatitis C and available liver biopsies were included. Baseline liver biopsies were read by 1 hepatopathologist using Metavir, as well as a fatty liver pathology protocol. Patients' baseline clinical, demographic, and virologic data were associated with the extent of steatosis (>33% vs. < or =33%), the type of fatty liver (no steatosis vs. steatosis only vs. NASH), and the stage of fibrosis seen on the liver biopsy. RESULTS: Seventy percent of patients were men and 80% were white. The mean age was 47.48+/-5.70 years, mean BMI was 29.01 +/-5.01 kg/m, and mean waist to hip ratio (W/H) was 0.90+/-0.08. Patients with higher grade of steatosis had higher BMI (32.83+/-6.26 vs. 28.49+/-4.62, P = 0.034), more likely to have genotype 3 (21.4% vs. 5.7%, P = 0.037) and advanced fibrosis (92.9% vs. 62.3%, P = 0.033) than those with lower grade of steatosis. Of these, only HCV-genotype 3 remained independently associated with higher grade of steatosis. When patients with superimposed NASH (n = 22) were compared with those with only steatosis (n = 49) and those without steatosis (n = 49), patients with superimposed NASH had more evidence of obesity (BMI: 30.64+/-5.23 vs. 29.90+/-5.35 vs. 27.33+/-4.07, P = 0.008; W/H: 0.97+/-0.06 vs. 0.91+/-0.08 vs. 0.87+/-0.07, P < 0.001), more commonly infected with HCV genotype 3 (14% vs. 12% vs. 0%, P = 0.036) and had more advanced fibrosis (95.5% vs. 75.5% vs. 42.9%, P < 0.001). Race, gender, and age did not affect extent of steatosis or presence of superimposed NASH. CONCLUSION: In conclusion, markers of obesity (BMI and W/H) and HCV genotype 3 are associated with the extent of steatosis and type of fatty liver. Higher grade of steatosis and presence of superimposed NASH are both associated with advanced hepatic fibrosis.

Fatty Liver↗
PubMed2003

Correlation between ammonia levels and the severity of hepatic encephalopathy.

PURPOSE: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis. METHODS: The diagnosis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (r(s)) were calculated. RESULTS: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (r(s) = 0.61, P < or = 0.001), venous total ammonia (r(s) = 0.56, P < or = 0.001), arterial partial pressure of ammonia (r(s) = 0.55, P < or = 0.001), and venous partial pressure of ammonia (r(s) = 0.52, P < or = 0.001). CONCLUSION: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammonia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels.

Adult↗
PubMed2003

Hemoglobinuria with ribavirin treatment.

Chronic hepatitis C virus is a major worldwide cause of hepatitis, cirrhosis, end-stage liver disease, and hepatocellular carcinomas. Combination therapy of ribavirin with short- or long-acting interferon-alpha is now the standard treatment of chronic hepatitis C. This therapy is associated with a wide range of side effects. Although hemolysis is almost an invariable result of ribavirin, black urine due to hemoglobinuria has never been previously reported. We recently encountered two cases of black urine (hemoglobinuria) in patients treated with combination therapy. Based on reports of dark urine in many of our patients, we suggest that this phenomenon may be more common than is currently appreciated. It indicates a marked degree of hemolysis, which prompts immediate measurement of hemoglobin level.

Adult↗