Hypotheses on the role of cytokines in peptic ulcer disease.

Helicobacter pylori is the cause of chronic type B gastritis and occurs in almost all patients with duodenal ulcers. Infection with H. pylori is characterized by an increased production of several inflammatory cytokines. Increasing evidence suggests a central role of these cytokines in the pathogenesis of H. pylori-associated gastritis and peptic ulcer disease. Cytokines may be crucial in the recruitment and activation of inflammatory cells and in stimulation of gastrin release. In addition to their proinflammatory properties, cytokines may also inhibit the ulcer occurrence by stimulation of prostaglandins and somatostatin release and by direct impairment of acid secretion. The balance of these factors may determine the clinical outcome of H. pylori infection.

Hyposensitivity to nerve stimulation in portal hypertensive rats: role of nitric oxide.

Portal hypertension goes along with vascular hyporeactivity, partly mediated by nitric oxide (NO). Interactions between the adrenergic nervous system and NO in portal hypertension are undetermined. We tested (1) whether superior mesenteric arterial beds of portal hypertensive rats have an altered sensitivity to periarterial nerve stimulation (PNS) and (2) the role of NO in modulating nerve-stimulated responses. Vasopressor responses to PNS (Hz, 2-32) were similar in preparations of partial portal vein-ligated (PVL, n = 12) and control (CON, n = 12) rats (60.0 +/- 6.7 and 47.8 +/- 6.1 CmH2O respectively) for 24 Hz (NS), but sensitivity of vessels of portal hypertensive animals displayed a significant rightward shift [Hz needed for 50% of maximal response (HZ50) being 15.5 +/- 0.4 and 12.9 +/- 0.6 for PVL and CON respectively, P < 0.001]. NO formation inhibition by N omega-nitro-L-arginine (10(-4) mol L-1) significantly increased responses to PNS (P < 0.05), the absolute values for 24 Hz being 101.4 +/- 11.7 cmH2O for PVL (n = 8) and 86.4 +/- 11.4 cmH2O for CON (n = 7) (NS). NO formation inhibition reversed the hyposensitivity in preparations of PVL, Hz50 being 13.9 +/- 0.5 and 13.2 +/- 0.2 for PVL and CON respectively (NS). Adrenergic receptor antagonism with prazosin (10(-7) mol L-1) and yohimbine (10(-6) mol L-1) inhibited PNS-mediated vasopressor reactivity (n = 6 per group, P < 0.001), confirming the nervous origin of vasoconstrictor responses. It is concluded that (1) portal hypertension goes along with a significant hyposensitivity to PNS and (2) this hyposensitivity is reversed by NO-formation inhibition

[Sphincter-conserving surgery in tumors of the middle and distal rectum: methods, indications and limitations]. / Sphinktererhaltende Chirurgie bei Tumoren des mittleren und distalen Rektums: Methoden, Indikation und Grenzen.

The purpose of this review is to summarize new developments in the surgical treatment of benign and malignant tumors of the rectum, focusing on oncological requirements and postoperative functional aspects which affect the quality of life. One of the developments is the transanal endoscopic microsurgical (TEM) approach to resection of adenomas and low risk early cancers in the rectum. Another focus is total rectum resection with colo-anal reconstruction with a colon pouch. This procedure reconstructs anorectal anatomy and provides nearly normal function. The reconstruction exists in two forms, (a) the colon-J-pouch and (b) the ileocecal interposition pouch (cecum pouch), which was developed at our institution. The review includes 33 consecutive patients with a rectum tumor. Standardized tumor-specific and functional staging determines which technique is used. 12 patients were operated on using the transanal endoscopic approach, 3 patients had a posterior proctotomy, another patient a transanal local excision and 17 patients total rectum resection with colon pouch reconstruction as described above.

[Helicobacter pylori resistance against metronidazole in Switzerland: implications for eradication therapy?]. / Resistenz von Helicobacter pylori gegen Metronidazol in der Schweiz: Implikationen für die Eradikationstherapie?

Gastroduodenal ulcers are strongly associated with Helicobacter pylori (HP) infection. Successful eradication drastically diminishes ulcer recurrence. Most of the eradication schemes include metronidazole (Flagyl). The present study was designed to establish the metronidazole resistance rate in Switzerland. Antral biopsies were taken in 153 patients with suspected ulcers (115 men, 38 women, mean age 46 +/- 16 [SD] years) during upper endoscopy for bacteriological testing. Metronidazole resistance (> 8 micrograms/ml) was found in 47/153 (31%) of the isolates. Resistance was found in no case to amoxicillin (Clamoxyl) (0/104 = 0%) and only in 3% (2/66) to clarithromycin (Klazid). Metronidazole resistance of HP in a third of the isolates studied is comparable to numbers found in other European countries. These findings raise the question whether eradication schemes including metronidazole without prior sensitivity testing are justified. Amoxicillin and clarithromycin appear to be valid alternatives.

[Which way ahead? Carcinoma of the exocrine pancreas, the gallbladder and the bile ducts--nonsurgical therapy in the locally advanced and in the metastasized stage]. / Wo bleibt der Fortschritt? Karzinome des exokrinen Pankreas, der Gallenblase und der Gallengänge--nicht-chirurgische Therapie im lokal fortgeschrittenen und metastasierten Stadium.

Carcinomas of the pancreas, gallbladder and bile ducts in inoperable stages can be treated with chemotherapy, radiotherapy and a combination of both modalities. Therapy is always palliative. In the past 20 years treatment results have not improved. Patients treated should be entered in controlled clinical studies with new substances randomized versus less toxic 5-FU or optimum supportive care. Pain and jaundice can be relieved by radiotherapy, bypass surgery and stent insertion. The choice of an option should be made according to patient characteristics and risk factors, as well as the possibilities and experience of the treating center.

[Pathophysiological and pharmacotherapeutic aspects of portal hypertension]. / Pathophysiologische und pharmakotherapeutische Aspekte der portalen Hypertonie.

Pharmacological prophylaxis and the therapy of complications of portal hypertension have recently been attracting more attention. This especially holds true for gastroesophageal variceal bleeding. Vasoconstrictors such as vasopressin, somatostatin, and beta-blockers, as well as vasodilators such as organic nitrates, alpha 2-adrenergic agonists and serotonin-antagonists, are currently used in clinical settings. The aim of this article is to delineate the present pathophysiological concepts accounting for the hemodynamic changes in animal models and patients with portal hypertension, and to summarize the mechanisms of action of the most frequently used pharmacological agents.

[Is flexible sigmoidoscopy as preventive measure for colorectal carcinoma in asymptomatic patients over 45 practicable?]. / Ist die flexible Sigmoidoskopie bei über 45jährigen asymptomatischen Patienten als Vorsorgeuntersuchung für kolorektale Karzinome praktikabel?

The efficacy of flexible sigmoidoscopy as a screening method for colorectal cancer is still undetermined, and a reduction in mortality due to this cancer by mass screening has not been demonstrated so far. An important precondition for the practicability of screening sigmoidoscopy is its acceptability by the persons to be screened. Acceptability was tested in 294 volunteers without abdominal symptoms from a general medical outpatients clinic. Mean age of participants was 58 years (45-86), 65% were men and 35% women. Sigmoidoscopy was judged harmless by 221 persons (75.1%), painful by 62 (21.1%), very painful by 11 (3.7%), and unacceptable by none. Every participant would have agreed to repeat the examination. In 36 patients 52 polyps were detected, comprising one carcinoma, 18 adenomas (in 15 patients), 32 hyperplastic polyps and one lipoma. We conclude that sigmoidoscopy was well accepted in this study and should be evaluated further as a mass screening method for colorectal cancer.

Intestinal phase of superior mesenteric artery blood flow in man.

Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to study the contribution of the small intestine to the postprandial splanchnic hyperaemia, and to determine the relative potencies of the major food components in the postprandial mesenteric flow response. Duplex parameters of vessel diameter, mean velocity, and volume flow were determined serially in the basal state and after stimulation. Flow parameters were significantly (p less than 0.05) increased after liquid and solid oral meals. Modified sham feeding did not alter mesenteric blood flow. Intestinal perfusion of an isocaloric liquid test meal induced flow increases comparable with oral intake. Superior mesenteric artery blood flow also significantly (p less than 0.05) increased after isocaloric and iso-osmolar loads of intraduodenal carbohydrate, fat, and protein meals. Responses were similar after the test meal, fat, and protein, but were significantly (p less than 0.05) less for carbohydrates. Different osmolar loads of saline did not affect flow responses. We conclude that the intestinal phase is the major regulator of the postprandial mesenteric blood flow response in healthy humans and that the chemical nature of food determines the mesenteric response pattern.

[Needlestick injuries in hospital personnel and the risk of hepatitis-B infection]. / Nadelstichverletzungen beim Spitalpersonal und Risiko der Hepatitis-B-Infektion.

The risk of employees of the University Hospital of Basel acquiring virus hepatitis B following needle stick injuries (NSI) was evaluated prospectively. Over four years, 555 NSI were reported, resulting in a mean incidence of 48 NSI/1000 persons working/year. Of the injured, 455 (82%) had previously been vaccinated against hepatitis B, 32 (6%) were HBsAg and/or anti-HBc positive, and only 65 (12%) were at risk for HBV infection. The origin of 365 (66%) of the needles implicated in the NSI was identified, and of these 15 (4%) had been contaminated with HBsAg-positive blood. None of the 555 persons with NSI developed hepatitis. We conclude that the risk of HBV infection following NSI is low at our institution, but general measures need to be enforced to reduce the incidence of NSI in view of the potential risk that other infectious diseases may be transmitted by NSI.

[Multicystic chylous lymphangioma in the mesentery of the small intestine]. / Multizystisches chylöses Lymphangiom im Dünndarm-Mesenterium.

In the search for metastases computed tomography and ultrasonography of the abdomen were performed in a 47-year-old man with a known malignant melanoma in the left lower leg. Numerous fluid-filled cavities, about 8 cm in diameter, were an incidental finding. He died two years after diagnosis of the melanoma, which had extensively metastasized. At autopsy a large multicystic tumour (21 x 15 x 8 cm) was found in the mesentery of the small intestine. The cysts were filled with chyle. Histologically they proved to be multicystic lymphangiomas. Mesenteric lymphangiomas are very rare, multicystic ones and manifestation in adults even more so.

[Sensitivity and specificity of a simplified, standardized 13C-urea breath test for the demonstration of Helicobacter pylori]. / Sensitivität und Spezifität eines vereinfachten, standardisierten 13C-Urea-Atemtests zum Nachweis von Helicobacter pylori.

A simplified 13C-urea breath test (UBT) for detection of Helicobacter pylori (Hp) infection was evaluated in 50 patients. Following upper gastrointestinal endoscopy the patients received 100 ml of a liquid test meal with 100 mg 13C-urea. Breath samples were obtained at baseline and 30 minutes respectively. The UBT was positive (difference of 13CO2 enrichment exceeding 5%) in 33/35 patients with culture-proven Hp infection and negative in 14/15 patients in whom microbiological culture, histology and a urease test (CLO-test) were negative. We conclude that in view of its high sensitivity (94%) and specificity (93%) the UBT is useful for rapid, non-invasive diagnosis of Hp infection.

Helicobacter pylori infection in healthy people: a dynamic process?

Epidemiological studies using serological tests have shown that a large proportion of healthy people have antibodies against Helicobacter pylori (anti-Hp). It is uncertain whether the presence of anti-Hp indicates active infection or only past exposure to the micro-organism. In this study we determined anti-Hp with a specific enzyme linked immunosorbent assay in 100 healthy volunteers who were at the same time investigated for active H pylori infection by means of the 13C-urea breath test. Forty nine per cent had a high anti-Hp titre, but only 24% had active H pylori infection. Our study suggests that a considerable number of healthy people previously infected with H pylori have spontaneously eliminated this microorganism. We suggest that the inability of ulcer patients to eliminate H pylori may be important in the pathogenesis of peptic ulcer disease.

Regulation of postprandial mesenteric blood flow in humans: evidence for a cholinergic nervous reflex.

Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to determine the physiological importance of postprandial blood concentrations of cholecystokinin octapeptide (CCK8), gastrin 17, secretin, and glucagon and to study whether a nervous cholinergic reflex mechanism has a role in the postprandial mesenteric blood flow response. Duplex parameters of vessel diameter, mean velocity, and flow volume were determined serially in the basal state and after stimulation. Changes were compared with baseline values. Superior mesenteric artery parameters were significantly increased over baseline values after a liquid test meal, but ingestion of saline did not cause any changes. Hormones infused simultaneously at postprandial concentrations did not change mesenteric blood flow. When they were infused at pharmacological doses, however, a significant increase in flow parameters was observed. Pretreatment with atropine significantly (p less than 0.05) reduced the mesenteric blood flow response to meal stimulation (57%). These data suggest that the four hormones tested are not of quantitative importance in regulating postprandial superior mesenteric artery blood flow. A cholinergic nervous reflex, however, participates in the control of food induced mesenteric artery flow changes.

Quantitation of intrinsic drug-metabolizing capacity in human liver biopsy specimens: support for the intact-hepatocyte theory.

Hepatic drug metabolism is decreased in patients with severe liver disease, but it is unclear to what extent this is due to altered hepatic blood flow or reduced intrinsic metabolic capacity. In this study we quantitated in needle-biopsy specimens the intrinsic capacity of liver tissue from 67 patients with mild liver disease (n = 36), chronic active hepatitis (n = 16) and cirrhosis (n = 15) to metabolize two model compounds in vitro. Hydroxylation of the low-extraction drug bufuralol resulted in the formation of 251 +/- 25 nmol 1'OH-bufuralol/gm wet wt/hr in mildly diseased liver tissue and was significantly (p less than 0.01) reduced in liver tissue exhibiting chronic active hepatitis (166 +/- 23 nmol/gm wet wt/hr) and cirrhosis (124 +/- 21 nmol/gm wet wt/hr). The formation rates of monoethylglycinexylidide, the main metabolite of the high-extraction drug lidocaine, varied widely and were not significantly different among the three groups. To relate the drug-metabolizing capacity to the hepatocyte content of liver tissue, morphometrical study was performed in the biopsy pieces originally submitted. The metabolic activity of each biopsy piece was then related to the fractional volume of hepatocytes it was calculated to contain. In mildly diseased liver tissue 355 +/- 35 nmol 1'OH-bufuralol/ml hepatocytes x hr or 12.4 +/- 1.0 mumol monoethylglycinexylidide/ml hepatocytes x hr- and in cirrhotic liver tissue 306 +/- 49 nmol 1'OH-bufuralol/ml hepatocytes x hr or 15.3 +/- 3.0 mumol monoethylglycinexylidide/ml hepatocytes x hr--were formed, respectively, and these differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Significance of family anamnesis in colorectal carcinoma]. / Bedeutung der Familienanamnese bei kolorektalem Karzinom.

To assess the familial risk of colorectal cancer among first-degree relatives of colorectal cancer patients, a tumour-related family history study was conducted in 1982-1988 on 184 patients (median age 60 [28-92] years). These family data were compared with the data recorded in the cancer register of the population of Basel. An enhanced risk among first-degree relatives was noted (relative risk: 1.8%; 95% confidence interval: 1.4-2.3). The enhanced risk was attributed exclusively to seven families involving 2-3 relatives each (the relative risk in these families being 34). In four of these seven families an autosomal dominant site-specific cancer of the colon (Lynch's syndrome I) was diagnosed. Hence, family case history of colorectal cancer patients enables the identification of relatives with a high risk for colorectal carcinoma.

[A year experience with extracorporeal shockwave lithotripsy of gallstones]. / Ein Jahr Erfahrung mit der extrakorporellen Stosswellenlithotripsie von Gallenblasensteinen.

43 patients with symptomatic gallbladder stones were treated by extracorporeal shockwave lithotripsy and oral bile acids. In all patients the stones were successfully fragmented during the first lithotripsy session. 33 patients underwent 2-4 treatment sessions. In 16 out of 43 patients the stones disappeared within 7.9 months. The rate of stone dissolution was dependent on the number and size of stones. 3 patients required surgery because of frequent colic in one case, cholecystitis in one case and lack of cooperation in one case. No important side effects were noted except mild pancreatitis 3 weeks after lithotripsy in one patient. Results at this center of extracorporeal shockwave lithotripsy combined with oral bile acids indicate that this treatment may become an alternative to cholecystectomy in patients with a small number (less than 3) of stones not exceeding 30 mm in diameter.

Effects of a cholecystokinin receptor antagonist on intestinal phase of pancreatic and biliary responses in man.

The present study was designed (a) to characterize the activity of loxiglumide as a peripheral cholecystokinin (CCK) antagonist in healthy human subjects, and (b) to determine whether CCK is a physiologic regulator of the intestinal phase of meal-stimulated exocrine pancreatic and biliary secretions in man. Intravenous loxiglumide (22 mumol/kg per h) was highly potent in antagonizing CCK8-induced pancreatic enzyme and bile acid secretion as well as pancreatic polypeptide release. The potency and selectivity of loxiglumide as an antagonist of CCK provides the tool for evaluating the role of CCK as a physiological mediator of meal-induced pancreatic and biliary responses in humans. Infusion of a liquid test meal into the duodenum evoked an immediate response of pancreatic enzyme and bilirubin outputs, respectively. Intravenous loxiglumide significantly inhibited the meal-induced pancreatic amylase output by 63% (P less than 0.05), lipase output by 43% (P less than 0.05), and bilirubin output by 59% (P less than 0.05). These data suggest that CCK is a physiological mediator of the intestinal phase of meal-stimulated pancreatic and biliary responses.

[ERCP under ceftriaxone antibiotic cover in patients with obstructive jaundice]. / ERCP unter antibiotischem Schutz mit Ceftriaxon bei Patienten mit Verschlussikterus.

The risk of cholangitis after ERCP has been reported to occur in up to 50% of patients with obstructive jaundice. Prophylactic antibiotics have therefore been advocated to reduce the risk. Here we report on the results of 46 patients with obstructive jaundice who were given 1 g of Ceftriaxone i.v. 30 to 60 min. prior to the procedure. Only one patient developed cholangitis with septicemia, which was treated conservatively. No side effects were observed in this group of patients. It is suggested that Ceftriaxone is an adequate prophylactic method to prevent cholangitis and septicemia in patients with obstructive jaundice.

Physical characteristics of indigestible solids affect emptying from the fasting human stomach.

Gastric emptying of indigestible solids depends on their size. It is not clear whether physical characteristics other than particle size affect emptying of indigestible solids from the fasting human stomach. We studied gastric emptying of three differently shaped particles, (cubes, spheres, rods) of either hard or soft consistency during the fasting state in human volunteers. The shape of indigestible particles did not affect their emptying. The area under the gastric emptying curve (AUC: particles x hour) was for hard cubes 24.7 (2.2), for hard spheres 27.9 (1.6), for hard rods 26.9 (2.7). All soft particles emptied faster than their identically shaped hard counterparts, but there was no difference among the three shapes (AUC for soft cubes: 29.2 (3.0), for soft spheres 32.0 (1.8), for soft rods 34.1 (1.2). If gastric emptying of hard and soft particles was compared independently of their shape, soft particles emptied significantly faster than hard ones: AUC 31.8 (1.2) v 26.5 (1.3) (p less than 0.01). In conclusion, the consistency but not the shape significantly affects gastric emptying. Specific physical characteristics other than size and shape may affect gastric emptying of indigestible particles which may be of importance in the design of drugs.