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During the period 1955 to 1974 inclusive, 826 patients developed Crohn's disease and were registered citizens of Stockholm County at the time of definite diagnosis. These patients were followed up and investigated with reference to the occurrence of and outcome after treatment for anal fistulae. These fistulae were recorded in 184 patients (23%). The incidence of anal fistulae increased the further distally the intestinal lesion was located. Healing followed local operation for anal fistula before curative intestinal resection in approximately 60% of the patients with small intestinal and combined ileocolic disease. However, patients with colonic Crohn's disease did not heal after such treatment. When curative intestinal resection was the primary procedure, 47% of the patients healed spontaneously. Small intestinal and combined ileocolic disease was associated with a good prognosis--90% were healed at follow-up, while patients with colonic disease had a poor prognosis. The combination of rectal Crohn's disease and anal fistula invariably led to proctocolectomy. [ABSTRACT FROM PUBLISHER]

Background: Inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, are now used frequently to treat hypercholesterolemia. We studied the effects of specific inhibition of cholesterol synthesis by one of these agents (pravastatin) on the hepatic metabolism of cholesterol in patients with gallstone disease who were scheduled to undergo cholecystectomy.Methods: Ten patients were treated with pravastatin (20 mg twice a day) for three weeks before cholecystectomy; 20 patients not treated served as controls. A liver specimen was obtained from each patient at operation, and the activities of rate-determining enzymes in cholesterol metabolism as well as low-density-lipoprotein (LDL)-receptor binding activity were determined.Results: Pravastatin therapy reduced plasma total cholesterol by 26 percent and LDL cholesterol by 39 percent (P less than 0.005). Serum levels of free lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, decreased by 63 percent (P less than 0.005), indicating reduced de novo biosynthesis of cholesterol. Microsomal HMG-CoA reductase activity, when analyzed in vitro in the absence of the inhibitor, was increased 11.8-fold (1344 +/- 311 vs. 105 +/- 14 pmol per minute per milligram of protein in the controls; P less than 0.001). The expression of LDL receptors was increased by 180 percent (P less than 0.005), whereas the activities of cholesterol 7 alpha-hydroxylase (which governs bile acid synthesis) and of acyl-coenzyme A:cholesterol O-acyltransferase (which regulates cholesterol esterification) were unaffected by treatment.Conclusions: Inhibition of hepatic HMG-CoA reductase by pravastatin results in an increased expression of hepatic LDL receptors, which explains the lowered plasma levels of LDL cholesterol. [ABSTRACT FROM AUTHOR]

Problem solving and critical thinking are important components of problem based learning (PBL). The driving forces are the students' interest, involvement and sense of responsibility. A curriculum comprising a combination of PBL and conventional instruction was introduced during the surgery course at Huddinge Hospital in the autumn term 1993. The results showed the level of knowledge attained by the students to be comparable with that attained under conventional instruction. The authors of the article conclude that good results can be obtained by introducing PBL in isolated sections of medical education within the framework of an otherwise traditional curriculum.

Operative liver biopsies were obtained from two male patients who developed gallstone disease during estrogen treatment of metastatic prostatic carcinoma. The heparin-sensitive binding of 125I-low-density lipoprotein (LDL) to liver homogenates (reflecting the expression of the LDL receptor) was determined, together with the activities of the rate-limiting enzymes in cholesterol synthesis [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase], bile acid production (cholesterol 7 alpha-hydroxylase), and cholesterol esterification (acyl CoA:cholesterol acyl transferase). The results were related to data available in 18 patients (5 male, 13 female) who underwent cholecystectomy because of gallstone disease. The hepatic 125I-LDL-binding activity was increased threefold compared with five controls, and the activity of HMG-CoA reductase was increased twofold. There was no major difference in the activities of cholesterol 7 alpha-hydroxylase or acyl CoA:cholesterol acyl transferase. The concentration of free and total cholesterol in liver microsomes was approximately 30% lower in the estrogen-treated men than in 11 controls. The results indicate that estrogen at pharmacological doses stimulates hepatic LDL-receptor expression and HMG-CoA reductase activity in men. The increased LDL-receptor expression could in part explain the enhanced plasma clearance of injected 125I-LDL and hence the reduction in plasma LDL cholesterol previously shown to occur in estrogen-treated men.

To study cholesterol metabolism in Crohn's disease and especially the effect of ileum resection, liver biopsy specimens were obtained from patients undergoing partial ileal resection because of Crohn's disease (n = 17) and patients with Crohn's colitis undergoing colectomy (n = 3). Gallstone-free patients (n = 16) undergoing cholecystectomy because of adenomyomas or polyps of the gallbladder served as controls. The mean levels of cholesterol 7 alpha-hydroxylase activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, rate-determining enzymes in bile acid, and cholesterol synthesis, respectively, were twofold to threefold higher in the ileum-resected patients than in the controls. Significant positive correlations were obtained between length of resected ileum and cholesterol 7 alpha-hydroxylase activity. Provided patients who had received total parenteral nutrition preoperatively were excluded from analysis, a significant correlation was also observed between length of resected ileum and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Significant positive correlations were also obtained between length of resected ileum and serum levels of 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) and lathosterol (a marker for cholesterol synthesis). The plasma levels of total and low-density lipoprotein cholesterol were negatively correlated to the length of resected ileum. The expression of hepatic low-density lipoprotein-receptor binding activity was determined in five of the patients and in three of the controls. A significant positive correlation was observed between 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein-receptor binding activity. The results show that malabsorption of bile acids leads to parallel stimulation of cholesterol synthesis, cholesterol degradation, and low-density lipoprotein-receptor expression in human liver. The resulting effect in the present patients was a significant reduction in low-density lipoprotein cholesterol.

The frequency of cholecystectomies was followed in the counties of Stockholm and Uppsala during an eight-year period (1969--1976). In both counties there was a highly significant decrease. This was mostly marked for males under 50 and females under 40 years in Stockholm and for females, regardless of age, in Uppsala. It is unlikely that these figures represent a decrease in the prevalence of gall-stone disease even if a small change is possible. A major alteration in the financing system of out-patient care has taken place during the investigated period and this has probably had an important influence on the cholecystectomy rate. Another important factor may be the consideration of a etiological factors other than gall-stones for minor abdominal disorders.

The effect of beta-adrenergic stimulation on specific insulin binding to isolated human fat cells was investigated at 24 degrees C and 37 degrees C. In the absence of glucose isoprenaline caused a 40% decrease in high affinity insulin binding at both temperatures. At 37 degrees C the reduction in binding was completely offset by the addition of glucose to the medium. A maximum effect of glucose occurred at 5 mmol/l. At 24 degrees C, however, there was no effect of glucose on insulin binding. The effects of glucose and isoprenaline on insulin binding were not related to the lipolytic activities these two agents. In conclusion, low amounts of glucose prevent catecholamine induced down-regulation of insulin receptor binding in human fat cells at physiological temperature.

This investigation was undertaken in order to (a) characterize the postprandial inflow of individual bile acids to the liver and (b) determine if peripheral venous bile acid levels always adequately reflect the portal venous concentration, or if saturation of hepatic bile acid uptake can occur under physiological conditions. In five patients with uncomplicated cholesterol gallstone disease, the umbilical cord was cannulated during cholecystectomy, and a catheter was left in the left portal branch for 5 to 7 d. The serum concentrations of cholic acid, chenodeoxycholic acid, and deoxycholic acid in portal venous and systemic circulation were then determined at intervals of 15 to 30 min before and after a standardized meal. A highly accurate and specific gas chromatographic/mass spectrometric technique was used. The sum of the fasting concentrations of the three bile acids averaged 14.04+/-4.13 mumol/liter in portal venous serum, and 2.44+/-0.31 mumol/liter in peripheral venous serum. The estimated hepatic fractional uptake of cholic acid was approximately 90%, and those of chenodeoxycholic acid and deoxycholic acid were 70-80%. This resulted in an enrichment of systemic bile acids in the dihydroxy bile acid species. In response to a standardized meal, portal venous bile acid concentrations increased two- to sixfold, with a peak seen 15-60 min after the meal. The maximum postprandial portal venous bile acid concentration averaged 43.04+/-6.12 mumol/liter, and the corresponding concentration in peripheral serum was 5.22+/-0.74 mumol/liter. The estimated fractional uptakes of the individual bile acids were not affected by the increased inflow to the liver. The peripheral venous concentrations of individual as well as total bile acids were well correlated with those in portal venous serum. The results (a) give a quantitation of postprandial bile acid inflow to the liver and (b) indicate that the hepatic uptake system for bile acids in healthy man cannot be saturated during maximal inflow of endogenous bile acids. Measurement of peripheral serum bile acids can thus give important information on the status of the enterohepatic circulation.

59 patients have been submitted to abdominal rectopexi according to Ripstein. The operative mortality was 5%, which was, however, not wholly due to the operation. The mortality-rate shows, however, that patients older than 60 years of age must be carefully evaluated preoperatively. The recurrence-rate was 5,4% with a mean observation period of 5 years. The method appears to be satisfactory for treatment of rectal prolapse.

Fasting serum concentrations of cholic acid, chenodeoxycholic acid, and deoxycholic acid were determined in healthy subjects and in patients with familial hypercholesterolemia before and during treatment with cholestyramine. The bile acids were analyzed by a specific isotope-dilution technique by using gas chromatography-mass spectrometry. Cholestyramine treatment did not change the fasting concentration of total bile acids, but the contribution of cholic acid was increased; those of chenodeoxycholic acid and deoxycholic acid were decreased. No decrease of fasting bile-acid concentrations in portal venous serum was seen in 2 cholestyramine-treated gallstone patients. The postprandial total bile-acid concentration was about 40% lower during cholestyramine treatment in healthy subjects, reflecting a reduced postprandial inflow of bile acids to the liver. This degree of interruption of the postprandial enterohepatic circulation may be sufficient to produce a near maximal bile-acid biosynthesis rate and to promote lowering of plasma cholesterol also in the fasting state. It is concluded that the postprandial bile-acid inflow to the liver may be more important as a regulator of bile-acid biosynthesis than is the fasting level of bile acids.

A short description is given of relevant anatomy and surgical techniques for transumbilical portal venous catheterisation in adults. Possible complications and applications of the procedure are discussed.

The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.

To study the regulation of lipid metabolism in human liver, we have developed assay systems for three rate-determining microsomal enzymes of hepatic cholesterol metabolism: 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (regulating cholesterol biosynthesis), cholesterol 7 alpha-hydroxylase (governing bile acid formation), and acyl-CoA:cholesterol acyltransferase (ACAT; rate limiting for cholesterol esterification). In addition, we have obtained an assay for low-density lipoprotein binding to its specific receptor in human liver, and we have studied a possible rate-determining enzymatic step in triglyceride biosynthesis, cytosolic phosphatidic acid phosphatase. These assays allow us to study the effects of metabolic perturbations on hepatic lipid metabolism in humans and thus to evaluate the important role of the liver in lipoprotein synthesis and degradation.

Eleven patients operated on for rectal prolapse, according to the method described by Ripstein, were examined pre- and postoperatively with cineradiography of the rectum. The patients were asked to fill in a questionnaire to evaluate their histories of constipation. There is no apparent anatomic explanation for postoperative constipation. One patient had a rectal stricture and another, a recurrence in the shape of an intussusception.

The results of treating 24 patients with anal fistulae and active intestinal Crohn's disease is reported. Four patients had multiple extended, seven high and ten low fistulae and three patients had sinus tracts. Seven patients with only minor discomfort were treated conservatively and five of them healed. Thirteen were treated by local surgery and ten subsequently healed. Four patients with rectal Crohn's disease and multiple fitulous systems were submitted to abdominoperineal excision. These results indicate that in patients without rectal involvement, conservative treatment and local surgery is indicated.

Acute intestinal obstruction in a women, aged 56, was caused by a highly malignant adenocarcinoma arising in a Meckel's diverticulum. Despite radical surgery, the tumour recurred after four months, and the patient died nine months after her first operation. This confirms the general bad prognosis associated with carcimomas of Meckel's diverticulum.

The fasting concentrations of ursodeoxycholic acid were determined in peripheral and portal venous serum of untreated (n = 12) and ursodeoxycholic acid-treated (n = 7) patients undergoing cholecystectomy. The levels of ursodeoxycholic acid were also determined in peripheral venous serum of 9 healthy subjects before and during treatment with ursodeoxycholic acid. Ursodeoxycholic acid, as well as cholic, chenodeoxycholic, and deoxycholic acids, were analyzed by a highly specific method based on isotope dilution-mass spectrometry. The fasting peripheral venous serum concentration of total (unconjugated plus conjugated) ursodeoxycholic acid averaged 0.14 mumol/L in the untreated gallstone patients and 0.19 mumol/L in the healthy subjects. The corresponding value in portal venous serum was 0.44 mumol/L. Treatment with ursodeoxycholic acid raised the level of this bile acid about 25-fold in portal as well as in peripheral venous serum. The proportion of unconjugated ursodeoxycholic acid was 34% in portal and 49% in peripheral venous serum of treated subjects. The mean hepatic uptake of ursodeoxycholic acid was calculated to be about 60% both in untreated and treated subjects. This uptake was significantly lower than that of cholic acid (83%). The hepatic uptake of ursodeoxycholic acid also tended to be lower than that of chenodeoxycholic acid (68%). This was mainly due to a lower hepatic uptake of unconjugated ursodeoxycholic acid (34%) compared with unconjugated chenodeoxycholic acid (49%). The relatively low hepatic uptake of unconjugated ursodeoxycholic acid explains why serum levels of the administered bile acid are higher during treatment with ursodeoxycholic acid than during treatment with chenodeoxycholic acid. Our results also give evidence that the hepatic uptake of ursodeoxycholic acid cannot be saturated under physiologic conditions.