Acute liver failure as the sole manifestation of relapsing non-Hodgkin's lymphoma.

Acute liver failure due to hepatic involvement by haematological malignancies is very rare, and usually has a rapidly fatal prognosis. We describe the case of a man who was treated for diffuse large B-cell lymphoma, and achieved a complete remission after eight courses of chemotherapy. He then presented with acute liver failure. Transjugular liver biopsy revealed massive infiltration by lymphomatous cells, with extensive necrosis. A CT scan did not show any evidence of extrahepatic lymphoma. The patient recovered from the liver failure following combined immuno-chemotherapy. Recurrence of the disease should be included in the differential diagnosis of patients with haematological malignancies and acute liver failure, even without evidence of extrahepatic involvement.

Treatment of refractory distal ulcerative colitis with short chain fatty acid enemas.

OBJECTIVES: To determine the efficacy and safety of short chain fatty acids (SCFA) in the treatment of refractory distal ulcerative colitis (UC). METHODS: Ten patients with distal UC who had failed to respond to rectal and oral therapy with 5-ASA and corticosteroids were treated with twice daily enemas containing sodium acetate 60 mM, sodium propionate 30 mM, and sodium butyrate 40 mM titrated to a pH of 7. Patients were assessed clinically (rectal bleeding, tenesmus, bowel motions), endoscopically, and histologically before and after 6 wk of therapy. In addition, patients gave a self-assessment of the efficacy of treatment. RESULTS: Five of the 10 patients responded clinically, and four of these had a clinical remission as reflected by a decrease in degree of bleeding (2.2 vs. 1.2, p < 0.05) and tenesmus (1.6 vs. 0.3, p < 0.05) and by global self-assessment. Endoscopic improvement occurred in five (6.78 +/- 0.83 vs. 4.44 +/- 2.7, p < 0.05). Histologically, no improvement was noted. No side effects were noted, and no patient's condition deteriorated. CONCLUSIONS: In this open-labeled study in patients with highly refractory distal UC, 50% had an overall clinical and endoscopic response. Forty percent of the patients assessed the treatment to be superior to previous treatments and expressed a desire to continue. This trial confirms other studies as to the efficacy of this treatment and further confirms the need for controlled trials of this promising therapy.

Is duodenal ulcer a seasonal disease? A retrospective endoscopic study of 3105 patients.

The monthly pattern of distribution of endoscopically diagnosed duodenal ulcer disease was evaluated for the years 1975-1989. A retrospective review of 3105 endoscopies performed for peptic disease was recorded and analyzed. Among them, 2020 endoscopies revealed duodenal bulb deformity, and 1035 revealed the presence of acute duodenal ulcer. Chi-square analysis of the data for goodness of fit revealed statistical differences for certain months. Slightly more patients with chronic deformity presented in June and November, whereas more patients with acute duodenal ulcer presented in July, November, and December (p < 0.001). The ratio of acute to chronic disease was nearly constant throughout the year. The Edwards chi 2 test for seasonal trends did not reveal any seasonality (p > 0.75). The differences observed in June-July and November-December, as compared with the rest of the year, were so small that they should not be relied upon for the clinical management of peptic disease.

Effect of clonidine on gallbladder contraction and small bowel transit time in insulin-treated diabetics.

Cholelithiasis is more prevalent in diabetics than in nondiabetics. Gallbladder dysmotility is supposed to be one of the causative factors. Reduced alpha-adrenergic tone has been demonstrated in the enterocytes of diabetic rats, and its correction by clonidine might explain the beneficial effect that the drug has on diabetic diarrhea. We therefore surmised that diabetic cholecystoparesis could also be due to alpha-adrenergic alterations. To test this hypothesis, we studied gallbladder contractions by real time ultrasonography, and small bowel transit time by lactulose hydrogen breath test, in 13 insulin-requiring diabetics before and after administration of the alpha-adrenergic stimulant clonidine (0.3 mg orally). That plasma levels were sufficient was evidenced indirectly by a fall in blood pressure. Clonidine significantly improved the rate of emptying (0.0193 +/- 0.00057/min vs. 0.0318 +/- 0.0027/min; p less than 0.005), but not the fasting and residual gallbladder volumes. Small bowel transit time was significantly prolonged after clonidine (169 +/- 17 min vs. 208 +/- 17; p less than 0.05). These results suggest that 1) reduced alpha-adrenergic tone corrected by clonidine may be present in the diabetic gallbladder, and 2) clonidine's antidiarrheal effect might be explained, at least in part, by a prolongation of the small bowel transit time.

Successful treatment of pancreatic pseudocyst with a somatostatin analogue and catheter drainage.

We report a patient with bile duct stone-induced pancreatitis who subsequently developed a large pseudocyst that became infected after endoscopic retrograde cholangiopancreatography (ERCP) was done for extraction of the stones. Percutaneous external drainage allowed control of the infection, but failed to seal the pseudocyst. We then treated the patient with a long-acting somatostatin analogue which shrunk the cyst within a week. Patients with pancreatic pseudocyst resistant to drainage should be offered a course of somatostatin before surgery is contemplated.

[Incompetence of the sphincter of Oddi in duodenal ulcer disease].

The association of post-bulbar duodenal scarring and incompetence of the sphincter of Oddi is rare. Radiographic and endoscopic procedures should exclude concomitant neoplastic disease invading the duodenum, and duodenal Crohn's disease. The pancreatico-biliary system should be visualized before attributing ampullar reflux to duodenal ulcer disease. The treatment is that of the primary disease.

[Pneumatosis cystoides intestinalis of the splenic flexure].

We describe a case of pneumatosis cystoides intestinalis with unusual localization and radiologic features. Barium enema showed multiple, rounded, submucosal masses, which were polypoid and airless and were localized to a 20 cm segment of the splenic flexure. There was no extraluminal gas on X-ray. Puncture of these formations via colonoscopic biopsy did not result in deflation of air. Surgical resection was performed and the classical features of pneumatosis cystoides intestinalis were found. Isolated splenic flexure involvement in conjunction with atherosclerotic cardiovascular disease may suggest that pneumatosis cystoides intestinalis is a reparative process after ischemic injury.

Campylobacter pylori in Israel: prospective study of prevalence and epidemiology.

Antral biopsy samples were taken from 147 patients undergoing gastroscopy. Campylobacter pylori was cultivated from 100 of these patients. C. pylori was isolated from 76% of the specimens showing any degree of histologic gastritis, but from only 11% of specimens with completely normal histology. A questionnaire was completed on all patients and included demographic, epidemiologic and clinical information. Sephardic origin, smoking, and a bad taste in the mouth were more prevalent in the campylobacter-positive group. Previous use of antibiotics was negatively associated with the presence of C. pylori. Histologically confirmed gastritis was highly associated with the presence of C. pylori, especially in the moderate or severe grades in which 84% of biopsy specimens were positive. C. pylori was also cultivated from 50% of patients with mild gastritis, in 88% of patients with duodenal ulcer and in 71% of patients with gastric ulcer. The presence of C. pylori in 11% of normal specimens and the absence of C. pylori in 24% of specimens with gastritis further raises the question of the exact role played by C. pylori in the etiology of gastritis.

Abnormal liver enzymes and ketonuria in hyperemesis gravidarum. A retrospective review of 80 patients.

We reviewed retrospectively a cohort of 80 patients with hyperemesis gravidarum hospitalized between 1976 and 1986 for the presence of abnormal liver enzymes and ketonuria. Thirteen (16%) had abnormal liver enzymes, generally less than four times the upper limit of normal. In this group, hyperemesis gravidarum began at the 14th week of pregnancy as compared to the 6th week in the normal enzyme group (p less than 0.01). Both groups were similar with regard to age, number of children and pregnancies, and duration of vomiting. Ketonuria was significantly more severe (p less than 0.01) in the abnormal enzyme group, implying a more severe state of starvation and dehydration. The correlation coefficient between the degree of ketonuria and level of liver enzymes was low for alkaline phosphatase (r = 0.18), GPT (r = 0.15), and GOT (r = 0.28). The concept that dehydration and starvation are important factors for the induction of liver cell injury is supported by our data. Lack of correlation between the degree of ketonuria and liver enzyme levels is suggestive of other mechanisms (hormonal, genetic) that may interact to produce transaminasemia.

Ornithine decarboxylase: an unreliable marker for the identification of population groups at risk for colonic neoplasia.

Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. Polyamines have been studied as potential markers of neoplastic diseases, including colonic cancer. Previous studies have pointed out the possible value of this enzyme as a biochemical marker of colonic neoplasia, we studied 100 patients undergoing diagnostic total colonoscopy. There were 40 normal controls and 20 patients in each of the following groups: 1) family members of patients diagnosed as having colonic tumors, 2) patients with adenomas, and 3) patients with colonic adenocarcinoma. Six forceps biopsies were obtained from the normal-appearing sigmoid mucosa for the analysis of ODC. No difference was found among the four groups studied. We therefore conclude that ODC is unreliable for clinical use as a biochemical marker for the identification of population groups at risk for colonic neoplasia.

Postpartum restoration of pregnancy-induced cholecystoparesis and prolonged intestinal transit time.

Pregnancy-induced cholecystoparesis and prolonged intestinal transit are well known, but their duration after delivery and any relation to the rapid decline of serum progesterone have not been studied in the early postpartum period. We studied gallbladder and small intestinal motor function in 10 women during the third trimester of pregnancy and in the second and fourth days postpartum, comparing the results to a control group of 8 women during the follicular phase of the menstrual cycle. Gallbladder motor function was evaluated by real-time ultrasonography and intestinal transit time was measured by the lactulose hydrogen breath test. Postpartum correction of gallbladder and intestinal motor function is early and is initially related to the fall of serum progesterone. Other as yet unknown mechanisms operate later to achieve normalization of gallbladder motor function.

Gallbladder contraction in patients with irritable bowel syndrome.

Impaired gallbladder contraction has been previously shown in pregnant women, in people with diabetes, celiac disease, and cystic duct syndrome, and in postvagotomy patients. In this study gallbladder contraction was measured by real-time ultrasonography in 32 subjects: 8 healthy controls, 12 diabetics and 12 with the irritable bowel syndrome. Contraction was expressed by four parameters: fasting gallbladder volume, residual gallbladder volume after maximal contraction, maximum percent of gallbladder emptied, and time elapsed until maximal contraction occurred. The main difference between the control subjects and the groups with diabetes and irritable bowel syndrome was found in the fasting and residual gallbladder volumes. Fasting volumes were twice as large in the irritable bowel syndrome (30.37 +/- 3.0 ml) as in the control subjects (15.15 +/- 0.69 ml, P less than 0.001). Residual volumes were also twice as great in those with irritable bowel syndrome, compared with the control subjects (12.91 +/- 2.18 ml vs. 5.6 +/- 0.58 ml, P less than 0.01). Similar, but less pronounced differences were found when the diabetic and the control subjects were compared. Fasting volumes were 21.7 +/- 2.62 ml for diabetic individuals vs. 15.15 +/- 0.69 ml for control subjects (P less than 0.05) and residual volumes were 10.87 +/- 2.69 vs. 5.6 +/- 0.58 ml (P = 0.1), respectively. The maximum percent emptied and the time elapsed until maximum contraction occurred were not statistically different. Also, no statistical difference was found between the diabetic individuals and those with irritable bowel syndrome in any of the parameters studied. Increased fasting and residual gallbladder volumes in the irritable bowel syndrome are changes that may promote sequestration and precipitation of cholesterol or calcium salts in the gallbladder of patients with lithogenic bile, as seen in diabetic individuals.

The lack of effect of metoclopramide on gallbladder volume and contraction in diabetic cholecystoparesis.

Impaired gallbladder contraction has been previously shown in diabetes mellitus. In this study gallbladder contraction was measured by real-time ultrasonography in 20 subjects (eight healthy controls and 12 diabetics) studied twice on 2 consecutive days, before and after intravenous metoclopramide injection. Contraction was expressed by fasting gallbladder volume and residual gallbladder volume after maximal emptying. Fasting volumes were significantly larger in the diabetics (22.4 +/- 2.1 ml) as compared to the controls (16.15 +/- 1.69 ml) (p less than 0.001). Residual volumes were also significantly larger in the diabetics (12.4 +/- 2.09 ml) as compared to the controls (5.6 +/- 0.58 ml) (p less than 0.001). The rate of gallbladder emptying was significantly (p less than 0.001) slower in the diabetics (0.0326 +/- 0.0056) as compared to the controls (0.0498 +/- 0.0066), but no difference could be shown in the diabetics after administration of metoclopramide (0.0368 +/- 0.0048). No difference was found in the diabetic group before and after injection of 10 mg metoclopramide. The results imply that diabetic cholecystoparesis is not entirely related to autonomic neuropathy since it is not corrected by metoclopramide, a known cholinergic stimulant.

Clinical, histological, and electron microscopic study of mast cell disease of the small bowel.

A patient with mast cell disease of the small bowel is described in whom clinical, histological, and ultrastructural studies served to delineate the characteristic features of the disease. Urticaria pigmentosa, steatorrhea, eosinophilia, absence of antireticulin antibodies, and submucosal nodularity seen on radiographic study of the duodenum were the clinical characteristics. The endoscopic appearance was that of severe exudative duodenitis. The histology of the small intestinal mucosa showed crypt cell destruction and villous atrophy. Marked infiltration of the lamina propria with mast cells, eosinophils, and neutrophils was also distinctive. The enterocytes retained their columnar epithelium, confirmed on electron microscopy. The fine structural abnormalities of the mast cells are demonstrated for the first time. Degranulated mast cells predominated within the lamina propria and none was seen among the epithelial layers. The mast cell nuclei were irregular, often binuclear, and showed loss of their normal heterochromatin pattern. In their cytoplasm only few granulated bodies were seen and even more rarely inclusions with whorls and scrolls. We conclude that the clinical, histopathological, and ultrastructural appearances in mast cell disease of the small bowel are distinctive and should be used as criteria for diagnosis. Care should be taken in the evaluation of the number of mast cells since the demonstration of these cells may be affected by various fixing and staining techniques.

Causes of iron deficiency anemia in an adult inpatient population. Effect of diagnostic workup on etiologic distribution.

The causes of iron deficiency anemia in a population of adults admitted to two Jerusalem hospitals within a period of 7 years were examined. About one half of the 262 patients with iron deficiency anemia were over 70 years old. The ratio of males to females exclusive of young females with menorrhagia was 1:1.8. Despite the combined use of various diagnostic procedures, no definite cause of iron deficiency anemia could be established in 34% of patients. Benign gastrointestinal lesions were found in about one half of the cases in both hospitals. The prevalence of GI neoplasms in hospital B with a more intensive use of endoscopic procedures was significantly higher than in hospital A (18% vs 5%, p less than 0.001). The relative usefulness of barium contrast vs endoscopic studies is illustrated by the fact that 22 diagnoses established by endoscopy were missed by barium studies, whereas only 2 of those established by barium studies were not visualized by endoscopy. A particularly high risk group were anemic males aged 50 to 69 years in whom the prevalence of GI neoplasms was 30%. These data indicate that reliance on traditional contrast radioscopy may result in misdiagnosis of a high proportion of gastrointestinal neoplasms.

Biliary lipids, bile acids, and gallbladder function in the human female: effects of contraceptive steroids.

Individuals who take contraceptive steroids or estrogens are at increased risk of developing cholesterol gallstones. The mechanisms of the increased stone formation are incompletely understood. In this study we report biliary lipid composition and secretion, bile acid composition and kinetics, and gallbladder function in a group of healthy, nonobese women taking a contraceptive steroid preparation. A comparable group of healthy women served as controls. Bile-rich duodenal fluid was obtained after stimulation of gallbladder contraction; bile acid, phospholipid, and cholesterol concentrations were determined. Biliary lipid secretion rate was measured by the marker perfusion technique. Bile acid distribution was determined by gas-liquid chromatography. The pool size, FTR, and synthesis rate of each bile acid were measured by using CA and CDCA labeled with the stable isotope of carbon, 13C. In some of the subjects gallbladder storage and emptying were measured during the kinetic study, by real-time ultrasonography. Contraceptive steroid use was associated with a significant increase in biliary cholesterol saturation and in the lithogenic index of bile. The rate of cholesterol secretion in the contraceptive steroid group was 50% greater than in the control (p much less than 0.001) and the rate of bile acid secretion was reduced (p less than 0.02). The total bile acid pool size was significantly increased by contraceptive steroids. The major increase occurred in the CA pool (p less than 0.04). The daily rate of enterohepatic cycles of the bile acid pool was decreased by contraceptive steroids from 6.6 to 4.3 (p less than 0.01). The only effect of contraceptive steroids on gallbladder function was a slower emptying rate in response to intraduodenal amino acid infusion. No index of gallbladder function correlated significantly with any parameter of bile acid kinetics in this small group of subjects. The findings confirm the lithogenic effect of contraceptive steroids and indicate that its causes are an increase in cholesterol secretion and a decrease in bile acid secretion.

Biliary lipids, bile acids, and gallbladder function in the human female. Effects of pregnancy and the ovulatory cycle.

To study the events that might lead to an increased risk of cholesterol gallstones, we examined biliary lipid composition and secretion and bile acid composition and kinetics at different stages of pregnancy or ovulation in young, nonobese, healthy women. Lipid composition and bile acid distribution were determined in duodenal fluid obtained in the fasting state and after stimulation of the gallbladder. Biliary lipid secretion was measured by the marker-perfusion technique. Bile acid kinetics were determined with cholic and chenodeoxycholic acids labeled with carbon13, by measuring the relative abundance of 13C in duodenal bile acids for 4--5 d. In a subset of patients we measured gallbladder storage and emptying during the kinetic study. The phase of the ovulatory cycle had no effects, but there were significant changes during pregnancy. The lithogenic or cholesterol saturation index of fasting hepatic and gallbladder bile increased during the second and third trimesters. The mean secretion rate of biliary lipids was not altered, but in the last two-thirds of pregnancy, cholesterol secretion increased in relation to bile acid and phospholipid secretion. There was a progressive decrease in the percentage of chenodeoxycholic acid and a similar increase in the percentage of cholic acid. The pool size of each major bile acid increased in the first trimester. Chenodeoxycholic acid and deoxycholic acid pools, but not cholic acid pools, subsequently decreased. The fractional turnover rate of both primary bile acids was slower during pregnancy. The synthesis rate of chenodeoxycholic but not cholic acid decreased in a linear manner during the first 20 wk of pregnancy. The rate of enterohepatic cycling of the bile acid pool was reduced throughout pregnancy. The volume of the fasting gallbladder and the residual volume after a physiologically stimulated contraction were directly correlated with bile acid pool size. The residual volume was also directly related to total bile acid synthesis.