Safety and efficacy of bariatric surgery in patients with advanced fibrosis.

BACKGROUND: Bariatric surgery is performed safely in non-alcoholic fatty liver disease (NAFLD) patients with minimal fibrosis (stage 1-2). However, the safety and potential benefits of bariatric surgery for NAFLD with advanced fibrosis (stage 3-4) remain unclear. This study was designed to compare the safety and efficacy of bariatric surgery in patients with biopsy proven advanced fibrosis to those with minimal fibrosis. METHODS: All patients who underwent bariatric surgery between 2005 and 2014 and had evidence of NAFLD with fibrosis score 3-4 (advanced fibrosis) based on the staging system defined by Kleiner et al. on intraoperative liver biopsy were included and compared with patients who had fibrosis score 1-2 (minimal fibrosis). The groups were compared for length of hospital stay after bariatric surgery and incidence of postoperative complications over a follow-up period of 1 year. An improvement in hepatic function tests before and 1 year after surgery was used as a parameter to evaluate for NAFLD improvement. RESULTS: Ninety-nine patients with F3-4 (group 1) and 198 patients with F1-2 (group 2) were included. Mean age (51.9 vs 50.1 years) and body mass index (46.4 vs 46.5 kg m-2) were similar in the two groups. Median serum aspartate aminotransferase (43 vs 30 U l-1; normal 10-40 U l-1) and alanine aminotransferase (40.5 vs 34 U l-1; normal 10-50 U l-1) were significantly higher in group 1 and improved 1 year after surgery. Median length of hospital stay after surgery was higher in group 1 than that in group 2 (4 days vs 3 days; P-value=0.002). The proportion of patients developing postoperative complications over 1 year was similar in both groups (36.4% vs 32.8%; P-value=0.54). CONCLUSIONS: Advanced fibrosis does not increase the risk of developing postoperative complications in medically optimized patients undergoing bariatric surgery. Improvement in serum transaminase levels suggests a reduction in hepatic necroinflammatory activity following bariatric surgery.

Liver Transplantation for Hepatocellular Carcinoma among African Americans in the United States.

BACKGROUND: There is increased prevalence of hepatocellular carcinoma (HCC) among African Americans (AA). Multicenter studies have shown advanced presentation, underutilization of treatment and decreased survival following liver transplantation (LT) among AA. However outcomes from single centers are not well reported. OBJECTIVE: To determine the outcome of AA undergoing LT for HCC at Cleveland Clinic, Cleveland, Ohio, between May 2007 and December 2009. METHODS: 245 consecutive patients undergoing evaluation and treatment for HCC within the mentioned time frame were studied, retrospectively. RESULTS: 80% of patients were male, 75.5% were Caucasian, 16.7% were AA and 7.8% were other ethnic groups. Compared to other ethnicities, AA subjects with HCC were more commonly female and were more likely to have hepatitis C virus (HCV) (83% vs. 51%, p<0.001). There were higher occurrence of HCV genotype 1 among AA compared to others among patients with this information (100% vs. 65%, p<0.001). In contrast to previous reports, there was no significant difference between the groups in terms of clinical presentation or management. 27% of AA underwent liver transplantation compared to 28% of the rest (p=0.88). Of the 68 patients who had LT, 9% died with no difference in post-LT survival between the two groups. CONCLUSIONS: HCV (and genotype 1) is a significant risk factor for HCC in the AA population. LT results in similar survival compared to other ethnicities. AA patients with HCC benefit equally from LT compared to other ethnicities.

Use of tegaserod along with polyethylene glycol electrolyte solution for colonoscopy bowel preparation: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Polyethylene glycol electrolyte solution (PEG-EL) used for colonoscopy preparation is not well tolerated by several patients. A significant number of patients have inadequate bowel preparation despite taking PEG-EL. AIMS: To determine the effect of prokinetic agent, tegaserod when given in addition to PEG-EL on patient tolerance, quality of colonic preparation and adverse side effects experienced. METHODS: In this prospective, randomized, placebo-controlled, double-blind study, a total of 130 patients scheduled for colonoscopy were enrolled. They were instructed to take three pills of either tegaserod 6 mg each or placebo (one pill twice on the day prior to and third pill in the morning on the day of colonoscopy) in addition to standard 4L of PEG-EL in the evening prior to the day of colonoscopy. Patient tolerance of preparation, quality of bowel preparation, overall satisfaction and adverse side effects were compared between the two groups. RESULTS: Fifty-five patients in placebo group and 58 patients in tegaserod group completed the study. There was no difference between the two groups in the tolerance of preparation, quality of bowel preparation, overall satisfaction and the side effects. CONCLUSION: Addition of tegaserod to polyethylene glycol electrolyte solution during colonoscopy preparation does not improve patient tolerance, quality of colonic preparation or the adverse side effects.

Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.

Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.

Hepatic iron and nonalcoholic fatty liver disease.

Increased iron is suspected to enhance hepatic injury associated with nonalcoholic fatty liver disease (NAFL). We evaluated the impact of iron accumulation on the outcome of NAFL. Patients with NAFL were identified from our database. Twenty-two clinicodemographic and 19 pathological features were available for each patient. Histological staining (Perls' Prussian blue), hepatic iron concentration (HIC), and hepatic iron index (HII) were determined. Data on follow-up, mortality, and cause of death were analyzed. In 65 patients with available liver biopsy blocks, HIC and HII were 1,171 +/- 717 microgram/g dry weight and 0.43 +/- 0.30 micromol/g/yr, respectively. Males had more iron accumulation (HIC: 1,514 +/- 836 vs. 859 +/- 389, P =.0001; and HII: 0.58 +/- 0.35 vs. 0.29 +/- 0.16, P =.0001). In type II diabetics, both HIC (977 +/- 769 vs. 1,301 +/- 659; P <.05) and HII (0.30 +/- 0.23 vs. 0.52 +/- 0.32; P <.05) were lower. Iron accumulation was not related to other variables analyzed. Increased iron was not seen in those with higher grades of fibrosis or other pathological features associated with the aggressive form of NAFL (hepatocyte necrosis, fibrosis, ballooning degeneration, and Mallory hyaline). Iron accumulation was not associated with increased overall mortality, liver-related mortality, or development of cirrhosis. In summary, in most patients with NAFL, significant iron accumulation is not seen. Additionally, in our series of patients with NAFL, iron is not associated with poor clinical or pathological outcomes.

A continuous quality improvement initiative reduces inappropriate prescribing of prophylactic antibiotics for endoscopic procedures.

OBJECTIVE: Despite the availability of guidelines, most gastroenterologists do not administer prophylactic antibiotics appropriately to patients having endoscopic procedures. In 1994 we recognized that in our endoscopy unit, many patients were receiving antibiotics without proper indication. We devised a continuous quality improvement initiative to analyze and improve this problem. METHODS: Divisional guidelines for the appropriate administration of prophylactic antibiotics for endoscopy were drawn up in 1995. By retrospective analysis of our comprehensive endoscopy database we compared the rate of prophylactic antibiotic administration, and the proportion of antibiotics that were indicated before and after adoption of the divisional guidelines. RESULTS: A total of 1427 endoscopic procedures were done during a 6-month period in 1994 (before adoption of guidelines). Of these, 55 (3.85%) received antibiotics. In a 6-month period in 1996 after adoption of guidelines, 1452 procedures were performed and 29 of these (1.99%) received antibiotics. The odds ratio for receiving antibiotics appropriately in 1996, compared with 1994, was 3.4 (chi2 p = 0.016). Given an annual volume of 2900 procedures in our endoscopy unit, approximately 54 patients will avoid unnecessary antibiotics, yielding a cost saving of $1128 per year. CONCLUSIONS: A divisional continuous quality improvement initiative on antibiotic prophylaxis for endoscopy significantly reduced the proportion of patients receiving antibiotics unnecessarily. This quality improvement initiative enhanced the quality of care for patients having endoscopy and yielded a small cost saving. These improvements were achieved with minimal effort and cost to the division.

Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.

BACKGROUND & AIMS: The spectrum of nonalcoholic fatty liver disease ranges from fatty liver alone to nonalcoholic steatohepatitis. Most previous studies have short follow-up and have not carefully delineated different histological types when determining clinical outcomes. The aim of this study was to compare clinical characteristics and outcomes of patients with different types of nonalcoholic fatty liver. METHODS: All liver biopsy specimens from 1979 to 1987 with fat accumulation were assessed for inflammation, ballooning degeneration, Mallory hyaline, and fibrosis. Biopsy specimens were also assessed for histological iron and hepatitis C RNA. Outcomes were cirrhosis, mortality, and liver-related mortality. RESULTS: Of 772 liver biopsy specimens, complete data were available in 132 patients. Fatty liver (type 1) did not differ from the other three types combined with respect to gender, race, age, or obesity. Cirrhosis was more common in the other types combined (22%) than fatty liver alone (4%; P

Severe intrahepatic cholestasis caused by amiodarone toxicity after withdrawal of the drug: a case report and review of the literature.

Cholestasis has been reported as a rare presentation among patients with severe liver injury secondary to amiodarone hepatic toxicity. We report an unusual case of amiodarone-induced cholestatic hepatotoxicity occurring after amiodarone had been discontinued and the initial abnormal liver function findings had improved. The patient, without jaundice at the initial presentation, developed severe jaundice about 4 months after withdrawal of amiodarone. Light and transmission electron microscopic examination of a specimen secured by computed tomographically guided liver biopsy was consistent with amiodarone hepatic toxicity as the cause of intrahepatic cholestasis. An abdominal ultrasound, endoscopic retrograde cholangiography, and dimethyl iminodiacetic acid and computed tomographic scans of the abdomen all failed to demonstrate any other causes for jaundice other than amiodarone toxicity. Thus, amiodarone hepatic toxicity may occur after drug withdrawal even if results of liver function tests improve. Histopathologic examination of a liver biopsy specimen is of value for diagnosis and prognosis. The liver biopsy findings, clinical course, and liver function test results are discussed, and the English-language literature on amiodarone cholestatic hepatotoxicity is reviewed.

Gender-dependent alterations in serum leptin in alcoholic cirrhosis.

BACKGROUND & AIMS: Leptin is a peptide that decreases food intake and increases energy expenditure. It is produced in fat cells, is stimulated by cytokines, and its levels in serum are higher in females. Because anorexia, hypermetabolism, and elevated cytokine levels are frequently observed in cirrhosis, we hypothesized that the serum leptin level would be elevated in cirrhosis. The aim of this study was to investigate the relationship of serum leptin to gender, body composition, and tumor necrosis factor (TNF). METHODS: Male (n = 18) and female (n = 10) abstinent alcoholic cirrhotic patients were studied and compared with control subjects (15 male and 8 female). Fat mass, fat-free body mass, and body cell mass were calculated by using H2[18O] and bromide dilution methodology. Serum leptin and TNF concentrations were measured by immunoassays. RESULTS: Fat mass was decreased only in male cirrhotics (P < 0.05), whereas body cell mass was decreased in both male and female cirrhotics (P < 0.01). Leptin levels were elevated in female (P < 0. 001) but not male cirrhotics compared with controls. When expressed per kilogram of fat mass, leptin was elevated in both male (P < 0. 01) and female (P < 0.01) cirrhotics. Women in both cirrhotic and control groups had higher leptin levels than men. TNF was elevated in both male and female cirrhotics and did not correlate with leptin levels. CONCLUSIONS: Cirrhotics have elevated serum leptin levels, which are related to both gender- and gender-dependent alterations in body composition.

Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations.

The exact cause, prevalence, and rate of progression of nonalcoholic fatty liver disease (NAFLD) are unclear because of a lack of agreement on the pathologic features associated with the different types of NAFLD, their clinical syndromes, and because of a lack of accuracy in the interpretation of these pathologic features. Studies of NAFLD would be aided by a consistent and standardized approach to the interpretation of pathologic features. The aim of our study was to assess interobserver and intraobserver variation in the histologic abnormalities associated with NAFLD. We identified histologic features of NAFLD as reported in the literature, and we identified patients with the diagnosis of NAFLD through the databases of two large institutions. Histologic parameters were evaluated for each liver biopsy specimen by four hepatopathologists and twice by two of the four pathologists (blindly). Interobserver and intraobserver concordance among the pathologists was measured by kappa statistics. Nineteen histologic parameters compartmentalized into steatosis, inflammation, liver cell injury, and fibrosis were evaluated on 53 liver biopsy specimens. Significant, substantial, or moderate concordance was present in only six items: the extent of steatosis, sinusoidal location of fibrosis, perivenular fibrosis, grade of fibrosis, ballooning degeneration, and the presence of vacuolated nuclei. Substantial or moderate concordance also was seen for interobserver readings for location of steatosis and periportal injury. Parameters of inflammation were not scored as reliably as parameters of fibrosis and cell injury. We conclude that only some histologic features previously reported in NAFLD (especially those with substantial and moderate concordance for both interobserver and intraobserver interpretation) are interpreted uniformly by experienced pathologists. These histologic features might prove useful for the development of a standardized and reliable pathologic scoring system that includes the full histologic spectrum of NAFLD and its various clinical outcomes.

Intronic and exonic sequences modulate 5' splice site selection in plant nuclei.

Pre-mRNA transcripts in a variety of organisms, including plants, Drosophila and Caenorhabditis elegans, contain introns which are significantly richer in adenosine and uridine residues than their flanking exons. Previous analyses using exonic and intronic replacements between two nonequivalent 5'splice sites in the 469 nt long rbcS3A intron 1 provided the first evidence indicating that, in both tobacco and Drosophila nuclei, 5'splice site selection is strongly influenced by the position of that site relative to the AU transition point between exon and intron. To differentiate between two potential models for 5'splice site recognition, we have expressed a completely different set of intronic and exonic replacement constructs containing identical 5'splice sites upstream of beta-conglycinin intron 4 (115 nt). Mutagenesis and deletion of the upstream 5'splice site demonstrate that intronic AU-rich sequences function by promoting recognition of the most upstream 5'splice site rather than by masking the downstream 5'splice site. Sequence insertions define a role for AG-rich exonic sequences in plant pre-mRNA splicing by demonstrating that an AG-rich element is capable of promoting downstream 5'splice site recognition. We conclude that AU-rich intronic sequences, AG-rich exonic sequences and the 5'splice site itself collectively define 5'intron boundaries in dicot nuclei.

Primary prophylaxis of variceal bleeding in cirrhosis: a cost-effectiveness analysis.

BACKGROUND & AIMS: Prophylaxis against the first variceal bleeding has been proposed to reduce morbidity and mortality in cirrhotic patients. No previous information is available regarding the cost-effectiveness of prophylaxis. The aim of this study was to compare the cost-effectiveness of variceal bleeding prophylaxis with propranolol, sclerotherapy, and shunt surgery in cirrhotic patients stratified by bleeding risk. METHODS: A hypothetical cohort was stratified according to bleeding risk. The natural history of cirrhosis with esophageal varices was simulated using a Markov model. Transitional probabilities extracted from published studies and costs were obtained from our institution's billing department. Sensitivity analyses were performed for important variables. RESULTS: Propranolol results in cost savings ranging between $450 and $14,600 over a 5-year period. The extent of cost savings depended on the individual patient's bleeding risk. In addition, propranolol increased the quality-adjusted life expectancy by 0.1-0.4 years. Sclerotherapy was significantly less cost-effective than propranolol and had no advantage on quality of life. Shunt surgery was effective therapy for prevention of bleeding but decreased life expectancy and quality of life in some risk groups and was not cost-effective. CONCLUSIONS: Propranolol is the only cost-effective form of prophylactic therapy for preventing initial variceal bleeding in cirrhosis regardless of bleeding risk.

Structural analysis of elements contributing to 5' splice site selection in plant pre-mRNA transcripts.

In vivo analyses of the cis-acting sequence requirements for pre-mRNA splicing in tobacco nuclei have previously demonstrated that 5' splice sites are selected by their position relative to AU-rich sequences within plant introns and by their degree of complementarity to the 5' end of U1 snRNA. To identify the specific nucleotide sequences promoting recognition of the 5' exon-intron boundary, multiple mutations have been introduced into a 22 nt AU-rich block positioned between two competing 5' splice sites in a derivative of pea rbcS3A intron 1. Transient expression of these mutant transcripts has delineated a 9 nt element positioned 30-38 nt downstream from the 5' splice site whose sequence composition affects 5' splice site choice. Uridine substitutions within this element do not alter 5' splice selection patterns, and, in fact, enhance recognition of the upstream +1wt 5' splice site slightly. Guanosine substitutions in this region, specifically creating an AG-rich AAAGGAGAGGCAGA motif (mutations shown underlined), reduce recognition of the upstream +1wt 5' splice site and enhance recognition of the downstream +106E 5' splice site. Cytosine substitutions at homologous positions marginally reduce recognition of the upstream 5' splice site. Additional mutations in this 9 nt element suggest that the AAAGGAGAGGCAGA motif acts as an specific 5' exon-defining element promoting recognition of downstream 5' splice sites, while AU-rich motifs promote recognition of upstream 5' splice sites. Mutations in an adjacent AU-rich region attenuate the effects of mutations in this short element but are not in themselves sufficient to alter 5' splice site selection. It is concluded that specific elements on both sides of the exon-intron boundary define the 5' splice site in this plant transcript.

Internal AU-rich elements modulate activity of two competing 3' splice sites in plant nuclei.

In vivo analyses using an autonomously replicating Agrobacterium/geminivirus vector have enabled identification of AU-rich intronic elements critical for 5' and 3' splice site selection in dicot plant nuclei and development of a model for pre-mRNA intron recognition in plant nuclei. To determine the minimal length, spacing and nucleotide compositions constraining recognition of the 3' boundary of an intron, two or four nucleotide substitutions have been introduced into the two AU-rich elements located between 50 and 66 nucleotides upstream from the 3' splice site of maize Adh1 intron 3. In each case tested, substitutions in the distal left element (-62 to -66) inactivate the downstream 3' splice site at -1 more effectively than substitutions in the proximal right element (-50 to -55). Guanosine or cytosine substitutions in either element reduce recognition of the -1 site significantly; adenosine substitutions have a less severe effect. Mutations in both of these AU elements additively block recognition of the downstream 3' splice site. The strong additive effect of these mutations supports a model in which short sets of AU islands bind interactive factors and cooperatively modulate usage of the downstream splice site. In contrast to the uridine requirements documented for the 3' terminus of plant introns, adenosines are partially interchangeable with uridines within this internal region of the intron.

Interactions across exons can influence splice site recognition in plant nuclei.

In vivo analyses of cis-acting sequence requirements for pre-mRNA splicing in tobacco nuclei have previously demonstrated that the 5' splice sites are selected by their position relative to AU-rich elements within plant introns and by their degree of complementarity to the U1 small nuclear RNA. To determine whether the presence of adjacent introns affects 5' splice site recognition in plant nuclei, we have analyzed the in vivo splicing patterns of two-intron constructs containing 5' splice site mutations in the second intron. These experiments indicated that the splice site selection patterns in plant nuclei are defined primarily by sequences within the intron (intron definition) and secondarily by weak interactions across exons (exon definition). The effects of these secondary interactions became evident only when mutations in the downstream 5' splice site decreased its functionality and differed depending on the availability of cryptic splice sites close to the mutant site. In beta-conglycinin chimeric transcripts containing multiple cryptic 5' splice sites, the presence of an intact upstream intron significantly increased splicing at the downstream 5' splice sites in a polar fashion without activating exon skipping. In a natural beta-conglycinin transcript, which does not contain cryptic 5'splice sites, mutation of the first nucleotide of the downstream intron activated an array of noncanonical 5' and 3' splice sites and some exon skipping.

U-rich tracts enhance 3' splice site recognition in plant nuclei.

The process of 5' and 3' splice site definition in plant pre-mRNA splicing differs from that in mammals and yeast. In mammals, splice sites are chosen by their complementarity to U1 snRNA surrounding the /GU at the 5' splice site and by the strength of the pyrimidine tract preceding the AG/ at the 3' splice site; in plants, the 3' intron boundary is defined in a position-dependent manner relative to AU-rich elements within the intron. To determine if uridines are utilized to any extent in plant 3' splice site recognition, uridines in the region preceding the normal (-1) 3' splice site of pea rbcS3A intron 1 were replaced with adenosines. This mutant activates two cryptic 3' splice sites (+62, +95) in the downstream exon, indicating that the uridines in the region immediately preceding the normal (-1) site are essential for recognition. Placement of different length uridine tracts upstream from the cryptic +62 site indicated that a cryptic exonic 3' splice site containing 14 or 10 uridine tracts with a G at -4 can effectively outcompete the normal 3' splice site containing an eight uridine tract with a U at -4. Substitutions at the -4 position demonstrated that the identity of the nucleotide at this position greatly affects 3' splice site selection. It has been concluded that several factors affect competition between these 3' splice sites. These factors include the position of the AU transition point, the strength of the uridine tract immediately preceding the 3' terminal CAG/ and the identity of nucleotide -4.

A cost analysis of alternative treatments for duodenal ulcer.

OBJECTIVE: To compare the costs of alternative strategies for the treatment of duodenal ulcer. DESIGN: A cost comparison using decision analysis. METHODS: A decision model was used to compare the costs per cure of an endoscopically documented duodenal ulcer for three initial treatment strategies: 1) H2-receptor antagonist therapy for 8 weeks, 2) antibiotic therapy for Helicobacter pylori infection plus H2-receptor antagonist therapy, and 3) urease test-based treatment. For symptomatic recurrences, secondary treatment strategies included empiric retreatment with the same or other regimen, and treatment based on repeat endoscopy-guided urease test or biopsy, with an assumption of subsequent cure. The cohort modeled for this analysis consisted of patients at low risk for a malignant ulcer. Probability estimates were derived from published clinical trials, cohort studies, and expert opinion. Side effects from combination therapy with antibiotics and H2-receptor antagonists and resulting costs were included from the perspective of a group practice model health maintenance organization. RESULTS: For all secondary treatment strategies, initial therapy with antibiotics for H. pylori infection plus an H2-receptor antagonist resulted in the lowest average costs per symptomatic cure when the prevalence or likelihood of H. pylori infection exceeded 66% to 76%; the costs ranged from $284 for secondary (re)treatment with empiric antibiotic and H2-receptor antagonist therapy to $398 for endoscopy-guided secondary treatment. Initial treatment with an H2-receptor antagonist resulted in the highest costs, ranging from $372 for secondary treatment with empiric antibiotic and H2-receptor antagonist therapy to $679 for endoscopy-guided secondary treatment. The results were not sensitive to the rates of duodenal ulcer recurrence after either treatment, to the cost of either treatment, or to prevalence of H. pylori. CONCLUSIONS: This cost analysis indicates that, regardless of the secondary treatment used for ulcer recurrence, initial therapy with antibiotics for H. pylori infection plus an H2-receptor antagonist provides the lowest costs per symptomatic cure. These cost savings and the lower recurrence rates associated with this treatment favor eradication of H. pylori as part of the initial treatment of duodenal ulcer.

Quantification of carbohydrate oxidation by respiratory gas exchange and isotopic tracers.

Estimates of glucose oxidation measured by indirect respiratory calorimetry and by [U-13C]glucose tracer were compared as a function of respiratory exchange ratio (RER) in 14 studies performed on 9 healthy adult subjects. RER was varied between 0.7 and 1.04, either by fasting or by infusing glucose. 13C enrichment of plasma glucose and expired CO2 were measured by mass spectrometry. The two methods gave similar results when the nonprotein respiratory quotient (NPRQ) was between 0.76 and 0.90. Glucose oxidation by the tracer method was quantified to be higher than that by respiratory calorimetry when NPRQ was < 0.76; it was lower than the respiratory calorimetry estimate when NPRQ was > 0.90. The discrepancy between the two methods at low RER may represent the contribution of gluconeogenesis, whereas, at high RER, the discrepancy may be the consequence of lipogenesis. We conclude that respiratory calorimetry and [13C]glucose tracer give comparable results only in a narrow range of RER. These data are important when the disposal of glucose is compared using these techniques in different metabolic states with varying respiratory quotients.