Transplantation of hepatocytes for prevention of intracranial hypertension in pigs with ischemic liver failure

BACKGROUND: How Helicobacter pylori infection affects gastric acid secretion is still unclear. METHODS: Gastric juice pH, ammonia concentration in gastric juice, serum gastrin level, and grade of gastritis in accordance with the Sydney System were determined for patients with gastric ulcer (GU) and duodenal ulcer (DU) before and after treatment with lansoprazole and amoxicillin, and results were compared with those of H. pylori-negative controls. RESULTS: Scores for H. pylori density, atrophy, metaplasia, and activity of gastritis in the corpus were higher in patients with GU, especially those with proximally located GU, than in those with DU. Gastric juice pH was significantly higher in GU patients than in DU patients and controls. After H. pylori eradication, gastric juice pH and serum gastrin levels in both GU and DU patients were significantly decreased to control levels. In patients without eradication, no significant changes in these factors were observed. CONCLUSIONS: These findings suggest that H. pylori infection and gastritis in the corpus suppress acid secretion and increase gastric juice pH, resulting in hypergastrinemia, and that eradication of H. pylori normalizes acid secretion and serum gastrin levels.     

Effect of Tityus serrulatus scorpion toxin on serum gastrin levels in anaesthetized rat

Scorpion toxin induces gastric secretion of acid and pepsin in rats. These effects seem to be mediated by the release of acetylcholine and histamine. However, the role of gastrin in the scorpion-toxin-induced gastric secretion is unknown. We describe the effects of the T1 fraction purified from Tityus serrulatus scorpion venom on serum and on antral tissue gastrin levels in anaesthetized rats. Gastrin levels in serum and in the antral mucosa were measured before and at intervals 5, 15, 30, 60, 90 up to 120 min after the intravenous injection of saline or the T1 fraction of scorpion venom (0.25 mg/kg) into anaesthetized rats. Antral G-cells were submitted to immunocytochemistry and electron microscopy. The data on gastrin were correlated with the gastric juice volume, and the acid and pepsin output increases induced by toxin. Scorpion toxin induced a significant increase in volume, acid output and pepsin output of gastric juice and gastrin serum levels 15-60 min after injection. Simultaneous measurements of antral gastrin levels did not show significant effects. The number of dense, intermediate and empty granules per microm(2) in the cytoplasm of antral G-cells was not significantly changed 60 min after saline or toxin injection. Scorpion toxin significantly increased serum gastrin; levels in rats.     

Eradication of Helicobacter pylori in patients with end-stage renal disease undergoing dialysis treatment

The aim of the present study was to examine the efficacy and safety of combination therapy with amoxicillin (AMPC), lansoprazole, and plaunotol for the eradication of H. pylori in dialysis patients. The subjects consisted of 15 dialysis patients (10 men and 5 women, mean age of 56 +/- 2.4 years) in whom H. pylori was found in the stomach. H. pylori status was evaluated by histology, culture and rapid urease test with biopsy specimens of the gastric mucosa. The patients were treated with AMPC 500 mg once a day for 3 weeks, lansoprazole 30 mg once a day for 8 weeks and plaunotol 80 mg three times a day for 24 weeks. In addition, the concentrations of serum gastrin and gastric juice ammonia were measured. Fourteen patients completed the treatment schedule, while one discontinued treatment because of nausea and diarrhea. Among the 14 patients, H. pylori was eradicated in 11 without any side effects (eradication rate 78.6%). Concentrations of gastric juice ammonia and serum gastrin were reduced significantly in patients who became H. pylori-negative. The present study indicates that combination therapy with AMPC, lansoprazole and plaunotol is safe and efficient for the eradication of H. pylori in dialysis patients. The results also suggested that elevated concentrations of gastric juice ammonia and serum gastrin in dialysis patients can be attributed, at least in part, to H. pylori infection.     

Codon 219 Lys allele of PRNP is not found in sporadic Creutzfeldt-Jakob disease

OBJECTIVE: To determine the prevalence of hypergastrinemia in cats with naturally developing chronic renal failure (CRF) and the correlation between gastrin concentration in plasma and severity of CRF. DESIGN: Cohort study. ANIMALS: 30 cats with naturally developing CRF and 12 clinically normal control cats. PROCEDURE: Gastrin concentrations in plasma were determined by double-antibody radioimmunoassay of blood samples obtained from cats after food was withheld 8 hours. Concentrations were compared, using a nonparametric Kruskal-Wallis ANOVA. RESULTS: 18 cats with CRF had high gastrin concentrations (median, 45 pg/ml; range, < 18 to > 1,333 pg/ml), compared with those for control cats (< 18 pg/ml). Prevalence of hypergastrinemia increased with severity of renal insufficiency. Three of 9 cats with mild CRF, 6 of 11 cats with moderate CRF, and 9 of 10 cats with severe CRF had high gastrin concentrations. Gastrin concentrations were significantly different between control cats and cats with CRF, regardless of disease severity. CLINICAL IMPLICATIONS: The potential role of high concentrations of gastrin on gastric hyperacidity, uremic gastritis, bleeding from the gastrointestinal tract, and associated clinical signs of hypergastrinemia (e.g., anorexia and vomiting) may justify use of histamine2-receptor antagonists or proton pump inhibitors to suppress gastric acid secretion in cats with CRF that have these clinical signs.     

Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to oxogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.     

Digoxin-quinidine interaction in patients with renal failure

Investigations were performed in order to study whether or not quinidine would exert similar effects on the serum digoxin concentration in patients with renal failure as in normal subjects. Fourteen out of fifteen patients showed a significant increase of the serum digoxin level after four days of quinidine application. This indicates, that the quinidine effect is not solely caused by a decrease of the renal digoxin clearance, although nine patients, not being hemodialysed, revealed a correlation between their creatinine clearance and the rise of the serum digoxin concentration after quinidine. As however, the patients on hemodialysis did not show higher digoxin levels than those treated conservatively, it is suggested that the degree of the uremic intoxication might be responsible for the observed correlation.     

Acute kidney failure in hypothermia

Two cases with acute renal failure after prolonged hypothermia are presented. Both patients were found in come, became rapidly uremic and required hemodilaysis treatment. Although the laboratory findings were typical of severe muscle damage, e.g. elevated levels of serum creatinine phosphokinase, serum lactic dehydrogenase and serum aldolase activities, visible "crush-injuries" were not found. Acute renal failure was characterized by extreme catabolism and severe metabolic acidosis. After 4 and 10 hemodialyses respectively, the patients became polyuric and finally were discharges with normal renal and muscle function. Hypotension with diminished renal perfusion and nontraumatic rhabdomyolysis due to prolonged hypothermia are regarded as the dominant pathogenetic factors in the acute renal failure.     

The effects of cysteamine on the upper gastrointestinal tract of children with cystinosis

The purpose of this study was to evaluate the effects of cysteamine on gastric acid output and serum gastrin levels in children with nephropathic cystinosis. We studied four children with nephropathic cystinosis receiving a dose of free base cysteamine of 14.35 mg/kg four times a day (range 12.30-18.80 mg/kg). Gastric acid was measured for the hour before and after administration of the medication. Serum gastrin levels were obtained at 0, 30, 60, and 90 min following the medication. Gastrointestinal anatomy was evaluated by endoscopy and biopsy. Following administration of the medication, all subjects showed an increase in gastric acid output. Mean acid output increased from 0.79 to 2.22 mEq/h. Mean gastric acid output adjusted for body weight increased from 0.03 to 0.09 mEq/kg per hour. Following administration of the medication, all subjects showed an increase in serum gastrin. The mean increase above the base value was 38.3 pg/dl. Two of the four subjects demonstrated visual and histological evidence of inflammation. Cysteamine has a marked effect on gastric acid production and serum gastrin, even at the dose used in children with nephropathic cystinosis. The clinical effect of this acid production is unknown but may be significant.     

Neuronal laterality in Parkinson''s disease with unilateral symptom by in vivo 1H magnetic resonance spectroscopy

PURPOSE: The aim of the present study was to investigate carcinoembryonic antigen (CEA), CA19.9, and CA72.4 in the serum and gastric juice of patients with gastric cancer. METHODS: Serum and gastric juice tumor markers CEA, CA19.9, and CA72.4 were measured in 59 patients who had gastric adenocarcinomas and were undergoing curative gastrectomy. The same markers were measured in 47 patients with benign gastric disorders and in 40 healthy subjects. The correlation between the serum and gastric juice levels of tumor markers and several clinicopathological factors were evaluated by univariate analysis. The significance of the tumor markers as prognostic factors was assessed both by univariate and multivariate analysis. RESULTS: The positivity rates of serum CEA, CA19.9, and CA72.4 were 57.6%, 38.9%, and 18.6% respectively. The positivity rates of gastric juice CEA, CA19.9, and CA72.4 were 62.7%, 30.5%, and 23.7% respectively. The combination of serum and gastric juice markers gave a positivity of 81.3%. There was no correlation between serum and gastric juice level of each tumor marker. Positivity of gastric juice markers did not correlate with prognosis. A significant difference in prognosis was observed between patients positive and negative for serum CEA and CA19.9. Multivariate analysis also revealed that serum CEA and CA19.9 levels were independent prognostic factors. CONCLUSIONS: Levels of both serum and gastric juice tumor markers continue to have only limited diagnostic usefulness in gastric cancer patients. CEA and CA19.9 in the preoperative sera are good prognostic factors, whereas the presence of tumor markers in the gastric juice does not play any prognostic role.     

Re-accreditation, re-certification and the postgraduate database

Anemia associated with ACE inhibitors is rare but it may cause problems especially in patients with renal disease. This study assessed the acute effect of trandolapril, an ACE inhibitor, on serum erythropoietin (EPO) levels in uremic and hypertensive patients. Trandolapril 2 mg/day was given orally for three days and blood samples were collected on the first and third day. Trandolapril led to a significant decrease in serum EPO in patients with chronic renal failure. Although the drug lowered serum EPO in hypertensive patients, this effect was not statistically significant. This drop in serum EPO levels may be one of the mechanisms by which ACE inhibitors cause anemia, or worsen anemia, in uremic patients and further studies are needed to clarify this point.     

Gastric ulcer: effect of healing on gastric acid secretion and fasting serum gastrin levels

In 15 patients with uncomplicated gastric ulcers, basal and peak gastric acid outputs and fasting serum gastrin levels were studied before and after healing. The mean basal acid output [4.0 +/- 1.3 (SEM) mEq H+/hr], the mean peak acid output (29.5 +/- 5.1 mEq H+/hr), and the mean fasting serum gastrin level (80.3 +/- 16.7 pg/ml) in these patients did not change significantly with healing. Failure of gastric secretory function to change with healing suggests that mucosal resistance factors are more important than gastric acid secretion in the pathogenesis of a gastric ulcer.     

The role of the beta-adrnergic receptor in the secretion of gastrin: studies in normal subjects and in patients with duodenal ulcers

Intravenous infusion of isoproterenol, a beta-adrenergic receptor stimulatory agent, increased serum gastrin concentration significantly more in patients with a duodenal ulcer than in healthy subjects. The rise in pulse rate, blood glucose concentration and in serum insulin was the same in both groups of subjects. Gastrin secretion was also increased significantly more in the patients than in the control subjects after a beef-meal. Basal serum gastrin concentrations were higher in the patients than in the control subjects and correlated to the rise in serum gastrin during both tests in the patients with a duodenal ulcer. Isoproterenol and meal stimulated gastrin secretion, expressed as percent of the basal value, were twice as higher in the patients as in the control subjects. The combined administration of isoproterenol and the meal had an additive effect on the rise in serum gastrin. Isoproterenol stimulated gastrin secretion was completely suppressed by propranolol, a beta-adrenergic receptor blocking agent, which had no effect on meal stimulated gastrin secretion. It is concluded that the mechanism of the hypersecretion of gastrin in patients with a duodenal ulcer did not involve a specific abnormality of the beta-adrenergic receptor or the receptor which recognized proteins and their digested products. There is no established role of beta-adrenergic receptor activity in the hypersecretion of gastrin in patients with duodenal ulcers. It is suggested that the beta-adrenergic receptor may have some yet unknown function unrelated to the acute secretory response of gastrin.     

Reproducibility of the acetylene rebreathe technique for determining cardiac output

Acute and subacute extrapyramidal movement disorders are rarely reported in uremic patients. We report three such cases with basal ganglia lesions. All three had advanced renal failure with high serum creatinine levels. One of the patients had a history of ischemic heart disease and acute pulmonary edema with hypoxemia. Another patient had experienced arterial hypotension during previous hemodialysis. The third had prominent metabolic acidosis. One of the patients developed generalized dyskinesias, whereas the other two developed gait disturbances. Neuroimaging studies in all three cases showed bilateral changes in the basal ganglia. The natural history was self-limiting with gradual improvement. Diminution of the basal ganglia lesions was demonstrated on follow-up imaging in two of the three cases. We conclude that acute or subacute movement disorders with bilateral basal ganglia lesions may occur in uremia. Hypoperfusion with global brain ischemia and selective vulnerability of the basal ganglia to uremic toxins may account for these lesions.     

RNA metabolism in uremic patients: accumulation of modified ribonucleosides in uremic serum. Technical note

To determine the metabolism of ribonucleic acid (RNA) in uremia, serum and urine levels of ribonucleosides in uremic patients were analyzed using reversed-phase high-performance liquid chromatography. The serum levels of xanthosine and all modified ribonucleosides were increased in undialyzed patients with chronic renal failure (CRF), and patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). The serum level of pseudouridine was markedly increased in all the uremic patients especially CAPD patients (32 times higher than normal). By contrast, the serum level of adenosine did not show any significant change in the uremic patients. Interestingly, the serum and urine levels of inosine were significantly decreased in all the uremic patients, suggesting that the production of inosine is decreased in uremic patients. The serum level of uridine was significantly elevated only in the HD patients. The serum levels of all ribonucleosides except inosine and uridine decreased significantly after HD. The urinary excretion of inosine, 1-methyladenosine, 1-methylguanosine, N2,N2-dimethylguanosine and N4-acetylcytidine was significantly decreased in the CRF patients, leading to the accumulation of these modified ribonucleosides in the uremic serum. CAPD patients showed markedly increased serum levels of modified ribonucleosides such as pseudouridine, 1-methylinosine, and N2,N2-dimethylguanosine and N4-acetylcytidine as compared with the HD patients. These results demonstrate that there was an altered metabolism of RNA in uremic patients with marked accumulation of modified ribonucleosides.     

Association between serum gastrin levels, gastric acid secretion and age in early gastric cancer

This study evaluated the effect of gastric acid secretion and serum gastrin response on tumor differentiation for early gastric cancer according to patients' age. We investigated the association between serum gastrin levels, gastric acid secretion and the histologic types of 335 early gastric carcinomas limited to the mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal ulcers. The preoperatively examined basal acid output, maximal acid output and peak acid output after administration of tetragastrin and serum gastrin levels before and after ingestion of a test meal were determined. Patients with differentiated cancer and duodenal ulcer showed a significant negative correlation between gastric acid secretion and age, while the former group also had a significant positive correlation between serum gastrin levels and age. On the other hand, patients with undifferentiated cancer did not show any such correlation between gastric acid and age, but showed a significant positive correlation between serum gastrin, integrated gastrin response and age. Patients with gastric ulcer did not show any such correlations. These data suggest that both low acid secretion and endogenous hypergastrinemia, especially in the elderly, may play an important role in differentiated and undifferentiated gastric carcinomas.     

Gastric juice neopterin in Helicobacter pylori infection

Neopterin, a pteridine compound produced by macrophages activated by interferon-gamma, is widely used to assess the activation of cellular immunity. An elevation in serum or urinary neopterin reflects immune activation in many different disorders, including viral infections, cancer, autoimmune diseases or acute myocardial infarction, but less attention has been paid to neopterin concentration in other biological fluids. The aim of the present study was to examine neopterin concentration in gastric juice. An association with the presence of Helicobacter pylori, a bacterium linked to the most common disorders of upper digestive tract, was also investigated. Gastric juice was obtained at endoscopy from 61 patients. Neopterin was determined by a radioimmunoassay and the presence of H. pylori was examined by urease test. The macroscopic finding of bile in gastric juice was associated with significantly higher neopterin levels compared to patients where no bile was noted (15.5 +/- 15.6 vs. 2.1 +/- 3.0 nmol/l, P < 0.001). However, similar concentrations were observed in the H. pylori positive and H. pylori negative patients (7.6 +/- 12.0 vs. 11.1 +/- 14.9 nmol/l). Even in the absence of macroscopic bile contamination, no significant difference could be found between the infected and uninfected patients (2.3 +/- 3.2 vs. 1.3 +/- 1.9 nmol/l), and the patients with duodenal ulcer and normal findings (3.8 +/- 4.6 vs 1.6 +/- 1.9 nmol/l). The contamination of gastric juice with bile represents the limitation for the use of neopterin as a marker of immune activation in the gastric mucosa. Rather than an index of immune activation, gastric juice neopterin concentration represents a marker of duodenogastric reflux.     

Effect of intrajejunal fat on meal-stimulated acid and gastrin secretion in man

The effect of intrajejunal fat infusion on meal-stimulated gastric acid and gastrin secretion was studied in 8 healthy volunteers. Intrajejunal fat significantly reduced the acid response to a meal, measured by intragastric titration, as compared to intrajejunal infusion of saline. While serum gastrin concentrations rose from fasting levels to a constant plateau after the meal when saline was infused, fat infusion resulted in a transitory decrease in serum gastrin concentration followed by a significant increase. It is concluded that inhibition of gastrin release only plays a minor role, if any, in the observed fat-induced jejuanl inhibition of meal-stimulated acid secretion.     

Inhibition of omeprazole induced hypergastrinaemia by SMS 201-995, a long acting somatostatin analogue in man

Whether the long acting somatostatin analogue SMS 201-995 (octreotide, Sandostatin) could inhibit the basal and meal stimulated hypergastrinaemia and hyperpepsinogenaemia induced by omeprazole was investigated. Eight healthy subjects were randomised to receive five day courses of SMS 201-995 (25 micrograms subcutaneously three times daily), omeprazole (40 mg once a day), a combination of both drugs, or placebo. Basal and meal stimulated serum gastrin and basal serum pepsinogen A and C values were measured the day before treatment, on day five of treatment, and the day after each course of treatment. Omeprazole caused significant increases in basal and meal stimulated peak and integrated serum gastrin values and pepsinogen A and C levels, which were still significantly raised the day after stopping omeprazole treatment. Giving SMS 201-995 with omeprazole significantly reduced any omeprazole induced increases in basal and meal stimulated peak and integrated serum gastrin levels; serum pepsinogen A and C values were significantly inhibited too. Serum gastrin values during combined therapy were not significantly different from those during placebo treatment, whereas pepsinogen A and C levels were still significantly raised. On the day after stopping combined therapy, basal and meal stimulated peak and integrated serum gastrin and serum pepsinogen C (but not pepsinogen A) levels were not significantly different from values obtained on the day after stopping omeprazole alone. SMS 201-995 without omeprazole significantly inhibited basal and meal stimulated peak and integrated serum gastrin levels. Pepsinogen A was also significantly inhibited by SMS 210-995, but the reduction in pepsinogen C failed to reach statistical significance. In conclusion, SMS 201-995 prevents basal and meal stimulated increases in serum gastrin during omeprazole therapy. This finding may have clinical importance in the few patients who have pronounced hypergastrinaemia because of profound long acting acid inhibition.     

Uremic medium increases cytokine-induced PAI-1 secretion by cultured endothelial cells

The overall fibrinolytic activity is depressed in patients with chronic renal failure where a prothrombotic state is described, thereby enhancing the risk of vascular occlusive events. The mechanism responsible for fibrinolysis derangement has not yet been elucidated. To evaluate the effect of the uremic environment on the fibrinolytic activity of endothelial cells, we studied plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) production by human umbilical vein endothelial cells (HUVEC) in culture, exposed either to uremic or normal sera, before and after cytokine stimulation. Twenty uremics were studied: 11 were on conservative dietary treatment and nine were on maintenance hemodialysis. Eight healthy subjects served as controls. Before cytokine stimulation, no difference in the HUVEC supernatant concentration of t-PA and PAI-1 was found among the groups studied. After stimulation with interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, the HUVEC supernatant levels of PAI-1 in the uremics were higher than in the controls, whereas the supernatant levels of t-PA did not differ. Our data provide evidence that uremic serum, in concert with IL-1 or TNF-alpha, can enhance PAI-1 secretion by endothelial cells, thereby depressing the fibrinolytic system. This impaired endothelial fibrinolytic response to hypercoagulation could favor vascular events, which are the major cause of morbidity and mortality in patients with chronic uremia.     

The gastric antisecretory activity of a phenothiazine molecule, LM 24056

The effect on the gastric secretion of the phenothiazine molecule N,N-dimethyl-10-(3-quinuclidinyl)-2-phenothiazine sulfonamide (LM24056) was studied in dogs equipped with gastric fistula and denervated pouch. The gastric stimulation was obtained either by exogenous stimulants (gastrin, gastrin + bethanechol, histamine) or by endogenous ones released by feeding gastrin; LM 24056 was infused i.v. 1. I.v. administration of 1.25 to 5 mg . kg-1 . h-1 of LM 24056 had a nearly complete inhibitory action on gastric juice secretion (acid and pepsin), on gastrin- and gastrin + bethanechol-stimulated secretion. The LM, 24056 concentration which produced 50% inhibition (IC50%) of acid and pepsin secretion was about 1.25 mg . kg-1 . h-1. 2. LM 24056 appeared to be unable to reduce the histamine-stimulated secretion. 3. I.v. administration of 1 to 30 mg . h-1 of LM 24056 reduced or abolished both gastric acid secretion and gastrin release. The IC50 was 5 mg . h-1 (or about 0.5 mg . kg-1 . h-1) for both responses. The possible mechanism of action of LM 24056 is discussed in comparison with those of H2-receptor antagonists, of atropine and of pirenzepine, respectively.