Seymour Mishkin

Complete regression of hepatocellular adenoma after withdrawal of oral contraceptives

SummaryA 28-year-old woman who complained of mild abdominal pain was found to have a large liver tumor. Angiography and needle biopsy established the diagnosis of hepatocellular adenoma. The tumor was felt to be unresectable because of its size, and no treatment was given other than withdrawal of oral contraceptives. Subsequent hepatic scintiscans documented complete resolution of the tumor over a 12-month period.

Fructose and Sorbitol Malabsorption in Ambulatory Patients with Functional Dyspepsia Comparison with Lactose Maldigestion/Malabsorption

The aim of this study was to study sugarmaldigestion/malabsorption in patients with functionaldyspepsia using H breath testing. End-expiratory breathH after separate 2 challenges with lactose (25 g), fructose (25 g), and sorbitol (5 g) were usedto determine malabsorption, as well as small boweltransit time (SBTT). Five hundred twenty patients withfunctional dyspepsia received all three challenges. Smaller groups were also tested after lactulose(10 g, N = 36) and glucose (50 g, N = 90) challenges.Fructose and sorbitol were closely linked with respectto absorption and malabsorption status. Only in the case of lactose maldigestion/malabsorption wasthere a greater than random prevalence of malabsorption(P < 0.001) for fructose and sorbitol. In contrast tolactose, ethnic origin did not influence fructose or sorbitol malabsorption, and femalespredominated among fructose and sorbitol malabsorbers.In Jews, the prevalence of lactosemaldigestion/malabsorption decreased in the age group of25-55 and subsequently rose after 55, while fructose and sorbitolmalabsorption decreased progressively with advancingage. With respect to small bowel transit time (SBTT), inthe case of sorbitol and lactulose, it was significantly greater (P < 0.05) than those for fructoseand lactose. Multiple sugar malabsorptions are commonwhen lactose maldigestion/malabsorption ispresent.

Hyperlipemia in acute pancreatitis: Metabolic studies in a patient and demonstration of abnormal lipoprotein-triglyceride complexes resistant to the action of lipoprotein lipase

Abstract A patient with acute pancreatitis and transient hyperlipemia is described. During the episode of pancreatitis the presence of plasma lipoprotein-triglyceride complexes with abnormal physical properties and chemical composition was demonstrated. In a polyvinylpyrrolidone (PVP) gradient column the behavior of these complexes was different from the behavior of fat particles of normal serums. In addition, they were characterized by a higher proportion of all lipoprotein constituents, with the exception of triglyceride; by a fatty acid composition similar to that of adipose tissue; and by unusual resistance to the action of postheparin lipoprotein lipase. The possibility that acute pancreatitis could produce augmented mobilization of free fatty acids or of triglyceride-lipoprotein complexes from adipose tissue is considered.

The glucose breath test: A diagnostic test for small bowel stricture(s) in Crohn's disease

The aim of this study was to determine whether an indirect noninvasive indicator of proximal bacterial overgrowth, the glucose breath test, was of diagnostic value in inflammatory bowel disease. Twenty four of 71 Crohns disease patients tested had a positive glucose breath test. No statistical conclusions could be drawn between the Crohns disease activity index and glucose breath test status. Of patients with radiologic evidence of small bowel stricture(s), 96.0% had a positive glucose breath test, while only one of 46 negative glucose breath test patients had a stricture. The positive and negative predictive values for a positive glucose breath test as an indicator of stricture formation were 96.0% and 97.8%, respectively. This correlation was not altered in Crohns disease patients with fistulae or status postresection of the terminal ileum. The data in ulcerative colitis were nondiagnostic. In conclusion, the glucose breath test appears to be an accurate noninvasive inexpensive diagnostic test for small bowel stricture(s) and secondary bacterial overgrowth in Crohns disease.

Re: Pimentel et al.--Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.

TO THE EDITOR: The article by Pimentel et al. in the December issue (1) concludes that 78% of irritable bowel syndrome (IBS) patients have evidence of small intestinal bacterial overgrowth (SIBO) and that 48% of subjects whose SIBO was eradicated no longer met the Rome criteria for IBS symptoms. Our experience and data do not support the very high prevalence of SIBO quoted in this article. We conducted multiple hydrogen breath tests on IBS patients, such as lactose, fructose, and sorbitol for symptom management, but also glucose and lactulose challenges for their diagnostic potential (2, 3). Our hypothesis was that although IBS patients have a constellation of symptoms, they have no identifiable organic pathology on routine testing. Therefore, the presence of a positive glucose breath test (GBT) or lactulose hydrogen breath test would indicate SIBO, which should be “pathological.” Our data showed that 28% of 100 consecutive patients with functional dyspepsia/IBS had positive lactulose hydrogen breath tests according to the criteria of Pimentelet al. (1). The bulk of our experience relates to the use of the GBT as an indirect test for SIBO (4) in 350 patients. Thirteen percent were GBT 1. The prevalence rose to 22.2% and 25.6% in the presence of elevated fasting hydrogen and methane, respectively (high background

Sulfamethoxazole-induced hepatic injury

15 ppm on at least three sugar challenges). Twenty-seven of a total of 60 GBT1 patients were treated with short courses of antibiotics. Symptomatic improvement and reversal of GBT positive to negative occurred in 92.6% and 74.1%, respectively. In our data, the patients who were GBT 1 were re-evaluated regarding possible explanations for this indirect evidence of abnormal SIBO. Etiologies such as diabetes mellitus with complications and history of previously treated and untreated GI infections were the most common. In the majority of patients we were able to suggest or hypothesize one of these clinical scenarios, but approximately 20% remained unexplained. These data did not support using GBT to exclude functional dyspepsia/IBS by identifying SIBO. From our study and interpretation of Pimentel’s data, there appears to be a subgroup of IBS patients who have SIBO on indirect testing and would benefit from a course of antibiotics. More patients need to be tested to help define this specific patient population. In the absence of more objective data and lack of a true gold standard test of SIBO, we believe that this will be a dynamic field that still needs to be explored.

The in vitro uptake and kinetics of release of palmitic acid and taurodeoxycholate from hamster small intestinal segments.

SummaryA patient with several episodes of jaundice associated with sulfamethoxazole therapy is described. In contrast to the histologic picture of hepatocellular necrosis with or without cholestasis that is generally associated with sulfonamide hepatotoxicity, in the present case a relatively pure cholestatic pattern was found. Associated clinical features, as well as the response to drug challenge, were compatible with a hypersensitivity mechanism. The patients lymphocytes did not undergoin vitro blast transformation upon stimulation with sulfamethoxazole or sulfamethoxazole-containing plasmas.

Effect of dl-ethionine on the intestinal absorption and transport of palmitic acid-1-14C and tripalmitin-14C. Role of intramucosal factors in the uptake of luminal lipids

Abstract 1. 1. Everted sacs from hamster proximal and distal small intestine were incubated for 10 min at 37° in a micellar solution containing labeled palmitic acid, sodium taurodeoxycholate and inulin. After incubation, efflux of the labeled compounds from the intestinal mucosa was measured by sequential 1-min rinsings in separate 20-ml volume of ice-cold Krebs-Ringer phosphate buffer for a total of 25 min. The radio-activity in each rinsing solution, tissue homogenates and serosal fluids was assayed. 2. 2. The uptake of labeled taurodeoxycholate and inulin by the proximal and distal small intestine was not significantly different. However, the amount of [I- 14 C] palmitic acid taken up by the proximal small intestine was significantly greater. 3. 3. A considerable fraction of the labeled substances taken up during the initial incubation could be released by rinsing. The distal small intestine released a greater fraction of labeled palmitic acid and its release appeared to be inversely related to the esterifying capacity of the intestine. Proportionately greater amounts of [ 3 H] taurodeoxycholate and [ 14 C]inulin than that of [1- 14 C]palmitic acid were released by both proximal and distal small intestine. 4. 4. Analysis of the kinetics of efflux of each substance indicated that efflux occurred from two compartments, one rapidly and one slowly turning over. The characteristics of efflux of labeled palmitic acid and taurodeoxycholate from the rapidly turning over compartment were similar to those of labeled inulin suggesting that they occupied the extracellular fluid space. The characteristics of efflux from the slowly turning over compartment were different for each substance, and no conclusions could be drawn regarding the location of this compartment. However, the finding that the efflux of [1- 14 C]palmitic acid and [ 3 H]taurodeoxycholate from this compartment was slower than that of [ 14 C]inulin indicate that superticial binding sites may be involved in the reversible uptake of these substances. In addition the ratio of [ 3 H]taurodeoxycholate to [1- 124 C]palmitic acid in this compartment was greatly in excess of the 10:1 ratio of the micellar incubation medium indicating that the efflux of [ 3 H]taurodeoxycholate exceeded that of [1- 14 C]palmitic acid.

Sorbital H2 breath testing when screening for malabsorption/intolerance and untreated celiac disease: Understanding the dose and concentration issues

The effect of DL-ethionine on the uptake and transport of lipid by the rat small intestine was investigated. A cottonseed oil emulsion containing (14)C-labeled tripalmitin or palmitic acid was administered intragastrically to rats pretreated with DL-ethionine, DL-ethionine plus methionine, or saline, and the rats were sacrificed 2, 4, and 6 hr later. Lipids from the plasma, the stomach, the colon, the luminal contents of the small intestine, and the wall of the small intestine were extracted, fractionated, and their radioactivity assayed. Ethionine markedly inhibited the uptake of lipids by the small intestine. This inhibition was not related to impairment of intraluminal lipolysis since analagous inhibitions were observed when palmitic acid or predigested triglyceride (TG), obtained through a jejunal fistula from normal animals, was administered instead of tripalmitin. Ethionine also inhibited the transport of lipid from the wall of the small intestine. A significant fraction of the administered lipid remained in the wall of the small intestine, and only a small fraction was transported to the blood stream. Although most of the wall radioactivity was in the form of TG, significant proportions were also found in the free fatty acid (FFA) and partial glyceride fractions, indicating a marked inhibition of mucosal reesterification to TG. The degree of inhibition of mucosal reesterification and the degree of inhibition of transport of wall lipids were directly related to the degree of inhibition of uptake of luminal radioactivity. This relationship suggests that the rate of reesterification, the level of mucosal FFA, and the rate of transport of intramucosal TG may be of importance in determining the extent of uptake of intraluminal lipid by the mucosal cells. Since a significant fraction of the wall radioactivity was in the form of TG, the decreased transport of wall lipids was attributed to an impairment of chylomicron completion due to inhibition of either the synthesis of chylomicron apoprotein or the association of preformed TG with the protein moiety of chylomicrons. Experiments with labeled amino acids support the first possibility.

Dairy sensitivity, lactose malabsorption, and elimination diets in inflammatory bowel disease.

Sorbital H 2 Breath Testing When Screening for Malabsorption/ Intolerance and Untreated Celiac Disease: Understanding the Dose and Concentration Issues