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A Schmassmann

Publications and source records attributed to A Schmassmann.

At least 55 records · Page 3Linked to original sources
PubMed1994

[Systemic karyomegaly with chronic interstitial nephritis. Discussion of the disease picture based on an autopsy case].

Systemic karyomegaly associated with interstitial nephritis was first described in 1978 by Mihatsch. Seven cases have been reported to date. We give an account of an autopsy case of systemic karyomegaly in a 30-year-old Italian man. Bizarre enlargement of nuclei was found in renal tubular epithelial cells, Schwann cells and in smooth muscle cells of vessels and bowel and, less obviously, in endothelial and adventitial cells of vessels, in alveolar epithelial cells and in astrocytes of the brain. These findings were associated with chronic interstitial nephritis, nonspecific hepatopathy, adenocarcinoma of the rectum and multiple sclerosis. The clinical course was marked by chronic renal failure, chronic haemodialysis and renal transplantation. The patient died 8 years after diagnosis in septic-toxic shock. The aetiology and pathogenesis of the disease are discussed.

Adenocarcinoma↗
PubMed1994

Persistent lack of somatostatin receptors in gastric mucosa of healing ulcers in rats.

BACKGROUND/AIMS: Growth factors and their receptors play a role in healing ulcers of the rat. Somatostatin is a putative growth factor in the gastric mucosa with multiple functions mediated by specific receptors. Therefore, the distribution of somatostatin receptors was evaluated in the gastric mucosa of healing ulcers. METHODS: Somatostatin receptors were measured in the gastric mucosa of healthy rats and of rats with cryoulcers and acetic acid-induced ulcers, using somatostatin receptor autoradiography with 125I-[Tyr3]-octreotide or 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28 as radioligands. Epidermal growth factor receptors were measured on adjacent sections with 125I-epidermal growth factor. RESULTS: High-affinity somatostatin receptors are present in the gastric fundic mucosa of healthy rats. In contrast, in healing ulcers, the somatostatin receptors are almost lacking in the ulcer edge or scar at 3, 7, 28, 49, and even 84 days after ulcer induction (83%-91% reduction). Similar results are obtained with cryoulcers and with acetic acid-induced ulcers. For comparison, the number of epidermal growth factor receptors are increased in the same healing ulcers. CONCLUSIONS: The persistent absence of somatostatin receptors for several months after ulcer induction may be of pathophysiological significance in ulcer repair and healing.

Acetates↗
PubMed1994

Cholecystokinin type B receptor antagonist PD-136,450 is a partial secretory agonist in the stomach and a full agonist in the pancreas of the rat.

Gastrin (cholecystokinin type B (CCK-B)) receptor antagonists may help to elucidate the physiological role of gastrin, have therapeutic potential as acid antisecretory drugs, and may be of use as adjuvant therapy for gastrin sensitive tumours. In binding studies, the gastrin receptor antagonist PD-136,450 had at least 1000 fold greater affinity for gastrin (CCK-B) than CCK-A receptors. In this study the biological activity of PD-136,450 was evaluated in conscious and anaesthetised rats. PD-136,450 antagonised gastrin stimulated acid secretion after subcutaneous (IC50: 0.28 mumol/kg; conscious rats) and intravenous (IC50: 0.17 mumol/kg; anaesthetised rats) administration. In basal secreting fistula animals, the compound stimulated acid output to 30 (5)% of the maximal response to gastrin. Stimulant activity was not caused by gastrin release. As an agonist PD-136,450 was about 350 times less potent than gastrin-17 on a molar basis. In addition, PD-136,450 was a powerful agonist of pancreatic secretion in anaesthetised rats. The specific gastrin antagonist L-365,260 inhibited the (partial) agonist activity of PD-136,450 in the stomach and the specific CCK-A receptor antagonist L-364,718 inhibited the agonist activity of PD-136,450 in the pancreas. It is concluded that the agonist effect of PD-136,450 is mediated via interaction with the gastrin (CCK-B) receptor in the stomach and the CCK-A receptor in the pancreas.

Animals↗
PubMed1994

Antacid provides better restoration of glandular structures within the gastric ulcer scar than omeprazole.

Mucosa of healed gastric ulcers displays histological abnormalities that are possibly the basis of ulcer recurrence. The influence of antacid and omeprazole treatment was studied on the quality of ulcer healing. Sixty four rats with gastric cryoulcers were treated daily either with placebo, antacid, omeprazole, or antacid plus omeprazole. Ulcer size was measured three times per week with a novel video endoscopic method. Prostaglandin generation (day 6), cell proliferation (day 8 and 15), height and cell composition of ulcer margin (day 8), and mucosal scar (day 15) were quantitatively assessed. Antacid, omeprazole, and antacid plus omeprazole significantly accelerated ulcer healing predominantly during days 3-8. Compared with placebo, the height of ulcer margin and mucosal ulcer scar was significantly increased in antacid (+7 and +9% respectively) and significantly decreased in omeprazole (-33 and -22% respectively) and antacid plus omeprazole (-26 and -18% respectively) treated rats. The number of bromodeoxyuridine labelled cells (+42%, day 8), epithelial cell mass (+42%, day 15), and the ratios of epithelial cells/connective tissue (+73%, day 15) and epithelial cells/gland lumen (+100%, day 15) were significantly increased in antacid treated rats. In conclusion, both antacid and omeprazole accelerate ulcer healing but antacid provides a better quality of healing. This advantage is lost by cotreatment with omeprazole.

Aluminum Hydroxide↗
PubMed1993

[12 years of endoscopic stone removal].

All 583 attempts at endoscopic clearance of biliary calculi, performed in the Gastrointestinal Unit, Inselspital Bern, were retrospectively analyzed from 1980 until 1991. The average age of the patients was 70; 56% were female and 44% male. In 1980, 26 ERCPs for bile duct stone removal were performed, whereas in 1991 the number had increased to 90. The substantial increase in 1991 occurred after introduction of laparoscopic cholecystectomy. Over the total period of 12 years all stones were removed endoscopically after papillotomy in 82%, while the success rate in 1991 was 90%. Morbidity was 5.4% and lethality 0.2%. Total morbidity did not change markedly. However, the number of severe complications requiring surgical repair was reduced from 1.7% between 1980 and 1986 to 0% between 1987 and 1991. These results suggest that endoscopic removal of bile duct stones is increasingly performed with high success and low complication rates.

Aged↗
PubMed1993

Cholylsarcosine, a new bile acid analogue: metabolism and effect on biliary secretion in humans.

BACKGROUND: Cholylsarcosine, the synthetic conjugate of cholic acid and sarcosine, is resistant to deconjugation-dehydroxylation during enterohepatic cycling in rodents and improves lipid absorption in a canine model of intestinal bile acid deficiency caused by distal intestinal resection. Experiments were performed to define its metabolism and effect on biliary secretion in humans. METHODS: The circulating bile acid pool was labeled with [14C]cholylsarcosine, and its turnover rate and biotransformation were determined by sampling bile daily. Cholylsarcosine (or cholyltaurine) was infused into the duodenum for 8 hours to define its effect on bile flow and biliary lipid secretion. RESULTS: Cholylsarcosine was lost rapidly from the enterohepatic circulation with a t1/2 of 0.5 days. The compound was not biotransformed by hepatic or bacterial enzymes. Cholylsarcosine had choleretic activity similar to that of cholyltaurine but induced more phospholipid and cholesterol secretion than cholyltaurine in four or five subjects. Infusion of cholylsarcosine (or cholyltaurine) at a rate averaging 0.6 mumol.min-1.kg-1 gave a biliary recovery of 0.2 mumol.min-1.kg-1; this value is the Tmax for active ileal transport of conjugated bile acids in humans. Laboratory tests for liver injury remained within normal limits. CONCLUSIONS: In humans, cholylsarcosine is not metabolized, is nontoxic, and has similar effects on biliary secretion as cholyltaurine. It appears safe to test in long-term studies the effect of cholylsarcosine on bile acid-deficiency states in humans.

Adult↗
PubMed1993

Recurrent bleeding after variceal hemorrhage: predictive value of portal venous duplex sonography.

OBJECTIVE: Risk assessment of recurrent variceal bleeding is essential for therapeutic decisions and is usually performed by endoscopy of the upper gastrointestinal tract. We studied the value of portal venous duplex sonography in predicting subsequent variceal bleeding in patients with cirrhosis. SUBJECTS AND METHODS: Thirty patients with cirrhosis who received sclerotherapy because of acute variceal hemorrhage for the first time (hemorrhage group), 30 patients with cirrhosis who had no previous hemorrhage (nonhemorrhage group), and 30 control subjects were examined prospectively. With the use of portal duplex and color Doppler sonography, flow direction, flow velocity, vein diameter, and response to respiration of portal vein vessels were measured and portosystemic collaterals and thrombosis of portal vessels were visualized. The results of these measurements and imaging findings were combined into a Doppler sonoscore. At entry into the study, all patients were classified on the basis of a sonoscore as having a low (sonoscore, < 4) or a high (sonoscore, > or = 4) risk for subsequent hemorrhage. During a mean follow-up period of 2 years (range, 15-36 months), the predictive value of this Doppler sonoscore was studied. RESULTS: In the hemorrhage group, the prevalence of recurrent hemorrhage was 40%, despite sclerotherapy, and the mortality rate was 60%. In patients with a Doppler sonoscore of 4 or more, the prevalence of recurrent hemorrhage was 67%, whereas in patients with a score less than 4, the prevalence was only 22% (p < .02). After sclerotherapy, endoscopic criteria showed no significant correlation with the prevalence of bleeding. In the nonhemorrhage group, the prevalence of variceal hemorrhage occurring was 13%, and Doppler sonographic criteria showed no significant correlation with the prevalence of subsequent hemorrhage. CONCLUSION: We conclude that Doppler sonography, performed after the first occurrence of variceal hemorrhage, provides useful prognostic information regarding the risk of recurrent hemorrhage. If these results are confirmed, Doppler sonography may be used to select the best method of treatment.

Blood Flow Velocity↗
PubMed1993

[Local or systemic treatment of inflammatory bowel diseases?].

Standard therapy of inflammatory bowel disease is based on the treatment with corticosteroids, sulfasalazine and 5-aminosalicylic acid. Depending on localization, extent and activity of the bowel inflammation, these drugs are administered topically, systemically or in combination. The advantage of the topical therapy is the lack of non allergic side effects. Ulcerative proctitis and left-sided colitis should, in the first approach, be treated topically with suppositories or enemas. In severe colitis, a combined systemic and topical therapy is useful. In Crohn's disease topical agents are of minor importance. 5-aminosalicylic acid is efficient in mildly active Crohn's disease and prevents relapse for some patients in remission. In severely active Crohn's disease, systemic corticosteroids have to be administered. Azathioprine, cyclosporin A and metronidazole are considered to be reserve drugs because of significant side effects. The clinical usefulness of new topical corticosteroids showing both high antiinflammatory effect and no systemic side effects is presently investigated.

Administration, Oral↗
PubMed1991

Active absorption of conjugated bile acids in vivo. Kinetic parameters and molecular specificity of the ileal transport system in the rat.

Active transport of conjugated bile acids by the distal ileum is required for efficient enterohepatic cycling of bile acids. Experiments were performed in the rat to obtain accurate values for Tmax and Michaelis constant (Km) of the absorptive area of the rat ileum and to define the structural specificity of the transport system. The distal fifth (20 cm) of the small intestine from an anesthetized animal with a biliary fistula was perfused using solutions of 10 taurine-conjugated bile acids; a flow rate was used that was sufficiently high such that unstirred water layer effects were negligible and the intraluminal concentration remained unchanged throughout the perfused segment. The absorption rate was equated with the rate of hepatic bile acid secretion. Values of Tmax (mumol/min.kg) were markedly influenced by bile acid structure: cholyltaurine, 12.9; ursocholyltaurine, 9.6; ursodeoxycholyl taurine, 5.0; and lagodeoxycholyl-(3 alpha,12 beta-dihydroxy-cholanoic acid)-taurine, 1.2. Decreasing the length of the side chain of ursodeoxycholate conjugates from 8 to 6 carbon atoms was associated with a modest increase in Tmax values from 5.0 to 9.1 mumols/min.kg. Values of Km correlated with Tmax values and ranged from 0.5 to 5 mmol/L, being highest for those bile acids that were best transported. The Tmax for cholyltaurine transport was not reached when the intraluminal concentration was as high as its critical micellization concentration, precluding the definition of its Tmax; however, for ursocholyltaurine, with a critical micellization concentration of 40 mmol/L, saturation of transport was clearly shown. Kinetic parameters could not be obtained for two common dihydroxy conjugates (chenodeoxycholyltaurine and deoxycholyltaurine) because at a transport rate of 2 mumols/min.kg systemic toxicity and death occurred. These studies define the maximal transport capacity of the rat ileum for taurine-conjugated bile acids; they indicate that the ileal transport system in the rat is of low affinity and high capacity for taurine conjugates of hydrophilic bile acids, and they show that both nuclear substituents and side chain length influence the transport rate of taurine-conjugated bile acids.

Animals↗
PubMed1990

Prevention of ursodeoxycholate hepatotoxicity in the rabbit by conjugation with N-methyl amino acids.

The effect of dietary administration of four different amino acid (N-acyl) conjugates of ursodeoxycholic acid on biliary bile acid composition, liver tests and hepatic morphology by light microscopy was examined in the rabbit. Each group of four to five rabbits received a chow diet supplemented with a single conjugate of ursodeoxycholic acid ursodeoxycholyl-glycine, ursodeoxycholyl-sarcosine, ursodeoxycholyl-taurine or ursodeoxycholyl-N-methyltaurine for 3 wks at a dose of 50 mg/kg/day; a control group received chow alone. After 3 wks of feeding, animals receiving ursodeoxycholyl-glycine or ursodeoxycholyl-taurine had hepatotoxicity associated with abnormal liver tests. Lithocholic acid made up 11% +/- 2.7% of biliary bile acids in the ursodeoxycholyl-glycine and 10% +/- 2.2% in the ursodeoxycholyl-taurine group. In contrast, animals receiving ursodeoxycholyl-sarcosine or ursodeoxycholyl-N-methyltaurine had neither hepatotoxicity nor abnormal liver tests and the proportion of lithocholic acid in biliary bile acids increased much less. Complementary studies showed that ursodeoxycholyl-sarcosine and ursodeoxycholyl-N-methyltaurine were not biotransformed during hepatic transport and were resistant to deconjugation and dehydroxylation in the rabbit. These experiments indicate that the N-methyl amino acid conjugates of ursodeoxycholic acid are nontoxic in the rabbit and resist deconjugation and dehydroxylation. Such resistance decreases formation of lithocholic acid in the colon, thus reducing its accumulation and consequent induction of hepatotoxicity.

Amino Acids↗
PubMed1990

Transport, metabolism, and effect of chronic feeding of lagodeoxycholic acid. A new, natural bile acid.

Ursodeoxycholic acid, the 7 beta-hydroxy epimer of chenodeoxycholic acid, is more hydrophilic and less hepatotoxic than chenodeoxycholic acid. Because "lagodeoxycholic acid," the 12 beta-hydroxy epimer of deoxycholic acid, is also more hydrophilic than deoxycholic acid, it was hypothesized that it should also be less hepatotoxic than deoxycholic acid. To test this, lagodeoxycholic acid was synthesized, and its transport and metabolism were examined in the rat, rabbit, and hamster. The taurine conjugate of lagodeoxycholic acid was moderately well transported by the perfused rat ileum (Tmax = 2 mumol/min.kg). In rats and hamsters with biliary fistulas, the taurine conjugate of lagodeoxycholic acid was well transported by the liver with a Tmax greater than 20 mumol/min.kg; for the taurine conjugate of deoxycholic acid, doses infused at a rate greater than 2.5 mumol/min.kg are known to cause cholestasis and death. Hepatic biotransformation of lagodeoxycholic acid in the rabbit was limited to conjugation with glycine; in the hamster, lagodeoxycholic acid was conjugated with glycine or taurine; in addition, 7-hydroxylation occurred to a slight extent (approximately 10%). When lagodeoxycholic acid was instilled in the rabbit colon, it was absorbed as such although within hours it was progressively epimerized by bacteria to deoxycholic acid. When injected intravenously and allowed to circulate enterohepatically, lagodeoxycholic acid was largely epimerized to deoxycholic acid in 24 hours. Surgical creation of a distal ileostomy abolished epimerization in the rabbit, indicating that exposure to colonic bacterial enzymes was required for the epimerization. Lagodeoxycholic acid was administered for 3 weeks at a dose of 180 mumol/day (0.1% by weight of a chow diet; 2-4 times the endogenous bile acid synthesis rate); other groups received identical doses of deoxycholic acid (hamster) or cholyltaurine, a known precursor of deoxycholic acid (rabbit). After 3 weeks of lagodeoxycholic acid ingestion, liver test results and liver appearance were normal. The total bile acid pool expanded by 37% in the rabbit, lagodeoxycholic acid composing 10% of biliary bile acids. In the hamster, the total bile acid pool was expanded by 95%, lagodeoxycholic acid composing 22% of biliary bile acids; biliary lipid secretion remained unchanged. Tracer studies indicated that the fractional turnover rate of lagodeoxycholic acid was high (157%/day, rabbit; 116%/day, hamster) because of its rapid epimerization to deoxycholic acid in the colon. These studies indicate that lagodeoxycholic acid, the more hydrophilic epimer of deoxycholic acid, is transported and metabolized as other dihydroxy bile acids but is much less toxic than deoxycholic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Transport, metabolism, and effect of chronic feeding of cholylsarcosine, a conjugated bile acid resistant to deconjugation and dehydroxylation.

To test the effect in rodents of chronic ingestion of a bile acid resistant to deconjugation, cholylsarcosine was synthesized and its transport, metabolism, and effect on biliary bile acid and biliary lipid composition were determined in rabbits, hamsters, and rats. Cholylsarcosine was shown to be well absorbed from the ileum but underwent little absorption from the jejunum or colon. When cholylsarcosine was administered in the diet at 140 mumol/kg.day, it was well absorbed and underwent little biotransformation during enterohepatic cycling; however, both bacterial deconjugation and dehydroxylation (without deconjugation) occurred to a small extent. With chronic feeding, cholylsarcosine accumulated to compose 24%-29% of circulating bile acids in all 3 rodent species. It was rapidly lost from the enterohepatic circulation, with a daily fractional turnover rate of 75%-150%, depending on the species. Cholylsarcosine caused no change in liver tests or hepatic morphology and did not influence biliary lipid secretion. When cholyltaurine was fed, it was also absorbed, but, in contrast to cholylsarcosine, was rapidly deconjugated and dehydroxylated to form deoxycholic acid. The deoxycholic acid accumulated in the enterohepatic circulation, as evidenced by a slow fractional turnover rate of 26%-40% per day, depending on the species. It is concluded that cholylsarcosine is absorbed from the ileum, has an enterohepatic circulation, does not undergo appreciable deconjugation or dehydroxylation in these rodents, and is nontoxic. In the rodent, the circulating bile acids can be somewhat enriched when a bile acid resistant to deconjugation is ingested; but the effect on the steady state biliary bile acid composition is less than that obtained when cholyltaurine is administered because cholyltaurine is biotransformed to deoxycholic acid, which in turn is absorbed and has its own efficient enterohepatic circulation.

Animals↗
PubMed1988

[MTBE litholysis and extracorporeal shock wave lithotripsy of gallstones].

Two new therapies for cholesterol gallstones, MTBE litholysis and extracorporeal shock-wave lithotripsy, have been developed and clinically tested in the last five years. In principle MTBE litholysis is applicable in 50-80% of gallstone patients and shock-wave lithotripsy in 25-30%. In MTBE litholysis a pigtail catheter is placed in the gallbladder by the percutaneous-transhepatic route using ultrasound-guidance. The gallstones can than be dissolved with the cholesterol contact solvent MTBE (methyl tert-butyl ether). With appropriate selection criteria the successful dissolution rate is 80-90%. Over 99% of radiolucent gallstones (1-3 stones per gallbladder) can be fragmented by extracorporeal shockwaves. Bile acids must be administered as adjuvant litholytic therapy, and thus the remaining fragments can be dissolved in 91% of cases within 2-18 months. In view of the limited experience with these procedures at the present time they are mainly indicated for symptomatic surgical high-risk patients and for those who strongly wish to avoid surgery. With careful evaluation of study data a broader indication policy may be possible in the future. The new methods and the essential study data are presented.

Cholelithiasis↗
PubMed1983

[Prostatic carcinoma. Incidence and significance of stage I - preclinical carcinoma].

58 consecutive prostatic glands of men without clinical prostatic cancer were investigated. In 40% of all over 50-year-old men (average age: 76 years) a prostatic cancer was found. The macroscopic diagnosis of stage I prostatic cancer was found to be unreliable. Since in routine necropsies the first and decisive evaluation of the prostate is based on macroscopic findings, most prostatic cancers are missed and only 3% are found on an average. To detect prostatic cancer with a minimal diameter of 3 mm reliably, 10-15 large histologic slides have to be investigated. The tumor size, the nuclear polymorphism, the frequency of perineural invasion and the number of inflammatory cells increase with histologic dedifferentiation. The results support the hypothesis, that the clinical prostatic cancer is in fact an enlarged, dedifferentiated stage I cancer. The clinical significance of stage I prostatic cancer is rather small because of the advanced age of the patients. Most of the patients die before the cancer becomes clinical.

Age Factors↗