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Biomedical subjects

Anne M Larson

Publications and source records attributed to Anne M Larson.

14 recordsLinked to original sources
PubMed2006

Incidence of minor complications and time lost from normal activities after screening or surveillance colonoscopy.

BACKGROUND: Few studies address the development of minor complications after screening or surveillance colonoscopy. OBJECTIVES: Our purpose was to examine in previously asymptomatic people the incidence of new symptoms after colonoscopy, risk factors for symptoms, and patients' perceptions of this examination. DESIGN: Prospective cohort study. Patients completed a standardized interview at 7 and 30 days after colonoscopy. PATIENTS: A total of 502 patients aged 40 years and older undergoing colonoscopy for colorectal cancer screening, surveillance, or follow-up of another abnormal screening test result. Patients were excluded if they had a history of inflammatory bowel disease, visible GI bleeding, or anemia. MAIN OUTCOME MEASURES: Incidence of minor complications and patient perceptions about colonoscopy. RESULTS: Minor complications occurred in 162 subjects (34%) before day 7 and in 29 subjects (6%) between day 7 and day 30, most commonly bloating (25%) and abdominal pain (11%). Six subjects had unexpected emergency department visits or hospitalizations within 30 days, including 2 with postpolypectomy bleeding. On multivariate analysis, minor complications were more common in women (odds ratio 1.78, 95% CI 1.21-2.62) and when the procedure lasted 20 minutes or longer. Bowel preparation was rated the most difficult part of the examination for 77%. Most subjects (94%) lost 2 or fewer days from normal activities for the colonoscopy itself, preparation, or recovery. CONCLUSIONS: Minor complications were common after screening and surveillance colonoscopy. The bowel preparation was the most difficult part of the examination for most patients. Most subjects lost 2 or fewer days from normal activities because of colonoscopy.

Adult↗
PubMed2006

Integrating palliative care for liver transplant candidates: "too well for transplant, too sick for life".

Chronic liver disease results in more than 1 million physician visits and more than 300,000 hospitalizations per year in the United States. More than 27,000 patients annually progress to end-stage liver disease (ESLD), liver failure, or death. Patients with ESLD experience such complications as encephalopathy, malnutrition, muscle wasting, ascites, esophagogastric variceal hemorrhage, spontaneous bacterial peritonitis, fatigue, and depression. Despite significant improvements in palliation, patients' quality of life diminishes and their disease will often inexorably progress. Liver transplantation, a valid treatment option, increases life and reduces many symptoms. With the current shortage of organs, up to 10% to 15% of these patients die without receiving an organ. Many patients also are not candidates for transplantation due to comorbid illness. In addition, some patients receive a transplant but succumb to complications of the transplant itself. Such patients and families face the conundrum of a potentially treatable yet often fatal illness. Through the case of a 55-year-old woman with a life-long history of hepatitis B virus infection who is awaiting transplant, we discuss the transplant eligibility process and the struggle with maintaining hope for a cure in the face a life-threatening illness. In all of these circumstances, the health care team must combine elements of palliative care with life-sustaining therapy to maximize the patient's quality and quantity of life.

Female↗
PubMed2006

Fulminant hepatitis A virus infection in the United States: Incidence, prognosis, and outcomes.

Acute liver failure (ALF) due to hepatitis A virus (HAV) infection is an uncommon but potentially lethal illness. The aim of this study was to identify readily available laboratory and clinical features associated with a poor prognosis among ALF patients with HAV infection. The presenting features of 29 adults with anti-HAV IgM positive ALF enrolled in the ALFSG_between 1998 and 2005 were reviewed. The HAV patients listed for transplantation by UNOS were also reviewed. Acute HAV accounted for 3.1% of patients enrolled in the ALFSG. At 3 weeks follow-up, 16 had spontaneously recovered (55%), 9 underwent transplantation (31%), and 4 had died (14%). A prognostic model incorporating 4 presenting features (serum ALT <2,600 IU/L, creatinine >2.0 mg/dL, intubation, pressors) had an AUROC for transplant/death of 0.899 which was significantly better than the King's College criteria (0.623, P = .018) and MELD scores (0.707, P = .0503). Between 1988 and 2005, the frequency of patients requiring liver transplantation for HAV in the UNOS database significantly decreased from 0.7 % to 0.1% (P < .001). In addition, the proportion of HAV cases enrolled in the ALFSG significantly decreased from 5% to 0.8% (P = .007). In conclusion, the frequency of HAV patients enrolling in the ALFSG and being listed for liver transplantation in the United States has declined in parallel. A prognostic index consisting of 4 clinical and laboratory features predicted the likelihood of transplant/death significantly better than other published models suggesting that disease specific prognostic models may be of value in non-acetaminophen ALF.

Adult↗
PubMed2006

Measurement of serum acetaminophen-protein adducts in patients with acute liver failure.

BACKGROUND & AIMS: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings. Acetaminophen-protein adducts are specific biomarkers of drug-related toxicity in animal models and can be measured in tissue or blood samples. Measurement of serum adducts might improve diagnostic accuracy in acute liver failure (ALF) patients. METHODS: We measured serum acetaminophen-protein adducts using high-pressure liquid chromatography with electrochemical detection in coded sera of 66 patients with ALF collected prospectively at 24 US tertiary referral centers. Samples were included from 20 patients with well-characterized acetaminophen-related acute liver failure, 10 patients with ALF owing to other well-defined causes, 36 patients with ALF of indeterminate etiology, and 15 additional patients without ALF but with known acetaminophen overdose and minimal or no biochemical liver injury. RESULTS: Acetaminophen-protein adducts were detected in serum in 100% of known acetaminophen ALF patients and in none of the ALF patients with other defined causes, yielding a sensitivity and specificity of 100%. In daily serial samples, serum adducts decreased in parallel with aminotransferase levels. Seven of 36 (19%) indeterminate cases demonstrated adducts in serum suggesting that acetaminophen toxicity caused or contributed to ALF in these patients. Low adduct levels were present in 2 of 15 patients with acetaminophen overdose without significant liver injury. CONCLUSIONS: Measurement of serum acetaminophen-protein adducts reliably identified acetaminophen toxicity, and may be a useful diagnostic test for cases lacking historical data or other clinical information.

Acetaminophen↗
PubMed2006

Endotheliitis in chronic viral hepatitis: a comparison with acute cellular rejection and non-alcoholic steatohepatitis.

Endotheliitis is an important histologic feature of acute cellular rejection (ACR) in the liver allograft. This change is not specific, however, and has been suggested to be associated with various liver diseases. End-stage liver disease owing to chronic hepatitis C is the leading indication for transplantation in North America, and its recurrence in allograft recipients is common. Because the presence of endotheliitis remains a diagnostic and therapeutic dilemma in transplant pathology, we investigated the prevalence and severity of endotheliitis in chronic liver diseases including hepatitis C. Endotheliitis was evaluated in 128 nontransplant liver biopsies of chronic liver diseases before therapy, including hepatitis C (HCV, n=62), hepatitis B (HBV, n=17), and nonalcoholic steatohepatitis (NASH, n=49). Eighty posttransplant biopsies with ACR were also reviewed. Subendothelial and supraendothelial endotheliitis were separately scored in the portal and central regions using a semiquantitative scoring system from 0 to 4. Pathologists were blinded to the clinical histories, and each biopsy was independently scored by 2 pathologists. Histologic activity index was also scored subsequently for cases of chronic HCV and HBV, using the modified Knodell (Ishak) score. Mean endotheliitis scores>1 were seen in 60%, 35%, and 6% of HCV, HBV, and NASH patients, respectively. The scores for portal subendotheliitis and supraendotheliitis were significantly higher in the viral hepatitis group than in the NASH group (P<0.01). There was no significant difference in the scores of endotheliitis comparing HCV to HBV. ACR group showed significantly higher scores in both portal and central subendotheliitis than any other group (P<0.00005). In the HBV and HCV groups with mean scores of portal subendotheliitis>1 (n=44), mean Ishak scores for portal inflammation and periportal injury were 2.43 and 2.34, respectively; whereas in those with less severe portal subendotheliitis (<or=1, n=35), Ishak scores were 1.66 and 1.37, respectively (P=0.00001 for portal inflammation and P=0.00001 for periportal injury, respectively). Our results suggest that minimal to mild subendotheliitis is common in portal veins in chronic hepatitis C and B, but is significantly less intense than that seen in ACR. The degree of endotheliitis correlates with inflammatory activity. These observations may help minimize the risk of overdiagnosing ACR when the patient has recurrent viral hepatitis, and may help clinicians avoid exposing patients to unnecessary immunosuppressive regimens when patients do not have cellular rejection.

Adult↗
PubMed2005

Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study.

Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended.

APACHE↗
PubMed2005

Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy.

Monitoring of intracranial pressure (ICP) in acute liver failure (ALF) is controversial as a result of the reported complication risk (approximately 20%) and limited therapeutic options for intracranial hypertension. Using prospectively collected information from 332 patients with ALF and severe encephalopathy, we evaluated a recent experience with ICP monitoring in the 24 centers constituting the U.S. ALF Study Group. Special attention was given to the rate of complications, changes in management, and outcome after liver transplantation (LT). ICP monitoring was used in 92 patients (28% of the cohort), but the frequency of monitoring differed between centers (P < 0.001). ICP monitoring was strongly associated with the indication of LT (P < 0.001). A survey performed in a subset of 58 patients with ICP monitoring revealed intracranial hemorrhage in 10.3% of the cohort, half of the complications being incidental radiological findings. However, intracranial bleeding could have contributed to the demise of 2 patients. In subjects listed for LT, ICP monitoring was associated with a higher proportion of subjects receiving vasopressors and ICP-related medications. The 30-day survival post-LT was similar in both monitored and nonmonitored groups (85% vs. 85%). In conclusion, the risk of intracranial hemorrhage following ICP monitoring may have decreased in the last decade, but major complications are still present. In the absence of ICP monitoring, however, patients listed for LT appear to be treated less aggressively for intracranial hypertension. In view of the high 30-day survival rate after LT, future studies of the impact of intracranial hypertension should also focus on long-term neurological recovery from ALF.

Adult↗
PubMed2005

Liver histology and alanine aminotransferase levels in children and adults with chronic hepatitis C infection.

BACKGROUND: Chronic hepatitis C is often a mild disease in children, but whether this is related to younger age or shorter duration of infection is unclear. Histologic severity has been shown to correlate with duration of infection regardless of age. OBJECTIVES: We compared histologic findings in children and adults with chronic hepatitis C while controlling for sex, duration of infection, hepatitis C virus (HCV)-RNA level, and genotype. METHODS: Twenty-one children and 52 adults whose infection was less than 20 years in duration and who had undergone a liver biopsy were included. Two blinded liver pathologists reviewed the liver biopsies and scored inflammatory activity and fibrosis using the modified Knodell scoring system. RESULTS: The groups were the same with respect to HCV-RNA level (P=0.8), and genotype (P=0.6) but differed in duration of disease (P=0.01) and sex composition (P=0.005). Covariate analysis showed no influence of genotype, duration of infection, or HCV-RNA level on outcome. In controlling for sex, children had significantly milder liver disease and alanine aminotransferase (ALT) elevations. CONCLUSIONS: With equal duration of infection, HCV-RNA level, and genotype, children have lower serum ALT levels and less severe liver disease than adults infected with HCV.

Adolescent↗
PubMed2004

Cardiopulmonary consequences of transjugular intrahepatic portosystemic shunts: role of increased pulmonary artery pressure.

GOALS: To determine whether increased pulmonary artery pressure (PAP) following transjugular intrahepatic portosystemic shunting (TIPSS) results in short-term mortality or cardiorespiratory complications. BACKGROUND: TIPSS is frequently performed for complications of cirrhosis. PAP increases following TIPSS; however consequences of this phenomenon are unknown. STUDY: Demographics, disease severity and etiology were recorded among patients undergoing TIPSS. PAP before and following TIPSS were measured and the relationship between PAP before and after TIPSS, and subsequent cardiorespiratory complications and mortality was examined. RESULTS: Thirty-one patients were enrolled (mean age 53 years, 74% men, 55% Child-Pugh class C cirrhosis). TIPSS was performed for variceal bleeding in 84% of cases. Ten patients (32%) died 5-20 days following TIPSS. PAP increased significantly following TIPSS (mean 20.8 mm Hg pre-TIPSS (95% CI 18.2-23.4) to 26.9 mm Hg post-TIPSS (95% CI 24.2-29.6, P = 0.0016). Congestive heart failure developed in 4 patients (13%), sepsis in 4 (13%), and ARDS in 8 (26%). Increased PAP following TIPSS was not associated with early mortality (P = 0.13), CHF (P = 0.31), or ARDS (P = 0.43). ARDS was the only significant predictor of short-term mortality following TIPSS (OR 18.7, P = 0.02 (95% CI: 1.5-232). CONCLUSION: PAP increases after TIPSS and cardiorespiratory complications are common, yet unrelated to increased PAP. ARDS is independently associated with increased risk of mortality after TIPSS.

Adult↗
PubMed2004

Effects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers.

Tacrolimus is an immunosuppressant approved for the prevention of rejection following transplantation and is a substrate for CYP3A and P-glycoprotein. A pharmacokinetic interaction between St. John's wort (antidepressant herbal product and inducer of CYP3A and P-glycoprotein) and tacrolimus was evaluated in 10 healthy volunteers. The pharmacokinetics of tacrolimus were obtained from serial blood samples collected following single oral doses (0.1 mg/kg) prior to and during an 18-day concomitant St. John's wort dosing phase (300 mg orally three times daily). Coadministration of St. John's wort significantly decreased tacrolimus AUC (306.9 microg.h/L +/- 175.8 microg.h/L vs. 198.7 microg.h/L +/- 139.6 microg.h/L; p=0.004) and increased apparent oral clearance (349.0 mL/h/kg +/- 126.0 mL/h/kg vs. 586.4 mL/h/kg +/- 274.9 mL/h/kg; p=0.01) and apparent oral volume of distribution at steady state (11.5 L/kg +/- 4.3 L/kg vs. 17.6 L/kg +/- 9.6 L/kg; p=0.04). St. John's wort appears to induce tacrolimus metabolism, most likely through induction of CYP3A and P-glycoprotein.

Administration, Oral↗
PubMed2003

Liver disease in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is an hereditary disorder that results in fibrovascular dysplasia with the development of telangiectasias and arteriovenous malformations. It predominantly involves the skin, mucous membranes, viscera, lungs, and brain. Hereditary hemorrhagic telangiectasia shows great genetic heterogeneity, and its phenotypes have been classified based on the recently identified mutated genes: endoglin (HHT-1) and activin-like kinase receptor-1 (HHT-2). Other families with phenotypic HHT do not bear these mutations; therefore, other genes are probably involved as well. Liver involvement is reported in up to 30% of persons affected by HHT. Large arteriovenous malformations in the liver can lead to significant complications, including high-output congestive heart failure, portal hypertension, hepatic encephalopathy, biliary ischemia, and liver failure. Embolization of large arteriovenous malformations in the liver remains controversial; however, liver transplantation can successfully eradicate these complications.

Genetic Predisposition to Disease↗
PubMed2002

Temporary support for acute liver failure.

GOAL: To review treatment approaches for temporary liver support of patients with acute liver failure (ALF). STUDY A MEDLINE: search of English language reports published between 1960 and 1999 and a manual search of bibliographies of relevant papers were performed. Studies of humans in whom non-orthotopic liver transplant (OLT)-based approaches were used were reviewed, including case reports, case series, review articles describing unpublished cases, and controlled trials. Relevant clinical information was extracted with emphasis on improvement in liver function, successful bridging to OLT, recovery without OLT, and death. There was a lack of more than one controlled trial for each therapy, and most case reports were anecdotal in nature; therefore, no statistical analysis was attempted. Predefined outcomes from individual patients were synthesized collectively into tables. RESULTS: Both cell-based and non-cell-based therapies for ALF appear promising. Preliminary experience has established the safety of these approaches, but current data are inadequate to evaluate efficacy. CONCLUSIONS: Routine use of artificial liver support systems cannot be recommended at this time. However, the established safety of cell- and non-cell-based liver support devices warrants additional prospective (Phase III) controlled trials among patients with ALF. We suggest an algorithm for management of patients with ALF that incorporates recent data.

Humans↗
PubMedDate not supplied

Pilot study of the relationship between histologic progression and hepatic iron concentration in chronic hepatitis C.

Hepatic iron deposition is common in patients with chronic hepatitis C (HCV) and may play a role in progression of liver disease. This pilot study examines the relationship between hepatic iron concentration (HIC) and histologic progression over time in patients with HCV. HIC was retrospectively measured in 14 patients with HCV who had 2 serial liver biopsies prior to the era of interferon therapy. The mean interval between biopsies was 56 +/- 46 months. Mean Knodell score worsened between first and second biopsies (10.0 +/- 2.8 versus 12.4 +/- 3.3; P = 0.007). There was increased portal inflammation (3.2 +/- 0.4 versus 3.6 +/- 0.5; P = 0.028) and fibrosis (1.8 +/- 1.3 versus 2.7 +/- 1.2; P = 0.002), but no significant change in piecemeal necrosis or lobular degeneration. There was no significant change in HIC between first and second biopsy (P = 0.66). However, HIC was noted to increase significantly among patients with cirrhosis on initial biopsy or those who progressed to cirrhosis (P = 0.009). In this pilot study, histologic progression in patients with precirrhotic HCV was not associated with an increase in HIC, whereas hepatic iron accumulation was observed in 3 patients once cirrhosis was present. The interaction between progression of hepatitis C and iron deposition warrants further study.

Adult↗