[Choosing wisely recommendations in gastroenterology]. / Klug-entscheiden-Empfehlungen in der Gastroenterologie.

The Choosing wisely initiative of the German Society of Internal Medicine addresses procedures which are inadequately implemented (deficits in patient care) as well as those which are performed too often but without proven benefits for patients (misuse or overuse of health services). Based on their guidelines, The German Society of Gastroenterology, Digestive and Metabolic Diseases has identified such aspects and incorporated them into the respective recommendations.

["Choosing wisely" in infectious diseases : Overuse of antibiotics - too few vaccinations]. / "Klug entscheiden" bei Infektionskrankheiten : Zu häufig Antibiotika - zu wenig Impfungen.

The "choosing wisely" recommendations of the German Society of Internal Medicine (DGIM) and its specialist societies address diagnostic and therapeutic procedures, which are of particular medical importance but applied too often or too rarely in clinical practice. The aim is to further improve treatment of patients. Important topics of overuse and insufficient treatment related to the diagnostics, therapy, prevention and exclusion of infectious diseases could be identified. These topics not only play an important role in the discipline of infectious diseases but are also relevant for other internal medical disciplines. These topics related to infectious diseases have also been integrated into the recommendations of the German Society of Gastroenterology, Digestive and Metabolic Diseases as well as the German Societies for Internal Intensive Care and Emergency Medicine, for Pneumology, for Nephrology and for Rheumatology. The pivotal issues of the recommendations are the inappropriate use of antibiotics and insufficient vaccination rates.

Efficient transformation of Dictyostelium discoideum with a particle inflow gun.

We report experiments to transform Dictyostelium discoideum using a simple home-made particle gun. Stable transformants were obtained at frequencies of up to 2500 clones/microg DNA. This is five times more than we achieve with the same vector using electroporation protocols. We also show that the particle inflow gun can be used for analysis of developmentally regulated gene expression in a transient assay.

[An evidence-based look at pharmacotherapy for gastroesophageal reflux]. / Medikamentöse Therapie der gastroösophagealen Refluxkrankheit Eine evidenzbasierte Ubersicht.

Acid-suppressant drugs predominate in the treatment of gastroesophageal reflux disease. Proton pump inhibitors (PPI) are the first-line choice in both reflux esophagitis and nonerosive reflux disease (NERD). H(2)-blockers play a minor role and should not be used in erosive esophagitis. Other drugs such as mucosa-protective compounds, prokinetics, and antacids do not play a role, either alone oder in combination with acid suppressants. Proton pump inhibitors should also be used in maintenance therapy which is not associated with significant risks. There is a general trend toward on-demand treatment (already established in NERD). In cases refractory to therapy, the choice of drug should be critically analyzed (in case H(2)-blockers are used), and increasing the PPI dose is recommended; persistent symptoms should lead to reevaluation of the diagnosis. Asymptomatic Barrett's esophagus represents no indication for treatment, which in symptomatic patients is carried out in the normal fashion.

Ballistic transformation of Caenorhabditis elegans.

A novel method to transform the nematode Caenorhabditis elegans is described. DNA coprecipitated with gold particles is shot at worms by means of a helium beam. Transformed worms are either identified by a dominant visible marker or selected by a conditional lethal system.

Fulminant Kaposi's sarcoma complicating long-term corticosteroid therapy.

Cutaneous Kaposi's sarcoma occurs rarely in patients receiving long-term corticosteroid therapy. The case of a rapidly progressive form of Kaposi's sarcoma occurring in a 29-year-old Palestinian woman with steroid-dependent Crohn's disease and familial Mediterranean fever is reported. Despite an extensive transfusion history, serologic and virologic studies failed to demonstrate exposure to the human immunodeficiency virus. Serologic and virologic evidence of concomitant cytomegalovirus infection, however, suggests possible pathogenic features similar to the acquired immunodeficiency syndrome-related form of Kaposi's sarcoma.

Increased somatostatin secretion from pancreatic islets of streptozotocin-diabetic rats in response to glucose.

Glucose stimulates somatostatin release from perifused pancreatic islets of diabetic rats 42-47 days after the induction of diabetes, and 48 h after withdrawal of insulin replacement therapy. The glucose effect is augmented by theophylline or glucagon. Basal somatostatin release and glucose-induced secretion are significantly higher in diabetic islets than in controls. It is suggested that glucose promotes somatostatin release by directly interacting with islet D cells but not via indirect pathways. Glucose-induced stimulation appears to be modulated by a D-cell adenylate cyclase/phosphodiesterase system. Reasons responsible for increased somatostatin secretion by diabetic islets include reduction in B-cell mass, suggesting that B cells may normally suppress the secretory activity of D cells.

Review article: metabolic consequences of long-term inhibition of acid secretion by omeprazole.

Metabolic sequelae of profound and long-lasting inhibition of gastric acid secretion by omeprazole have largely been neglected. Data from long-term studies suggest that vitamin B12 stores decrease slightly over several years, although this was not clinically relevant within the first 4 years of therapy. Additionally, it cannot be completely ruled out that patients with an increased iron demand may develop iron deficiency, but data available at present do not provide any evidence that iron malabsorption is to be expected under normal conditions. Protein homeostasis and calcium metabolism seem to be unaffected by long-term omeprazole therapy. Based upon present experience, serum cobalamin concentration should be monitored in patients undergoing omeprazole therapy for several years.

Serum gastrin levels during long-term omeprazole treatment.

Serum gastrin was determined in 33 patients during treatment with the proton pump inhibitor omeprazole. After 4 weeks of therapy, gastrin levels increased to a median of 55 pg/ml compared to 15 pg/ml prior to omeprazole (P less than 0.001). There was a close correlation (r = 0.939; P less than 0.001) between pre-treatment gastrin and levels at 4 weeks. Comparison of serum gastrin concentrations at 1 month of omeprazole with levels at 6 (n = 21) and 12 months (n = 12) continuous therapy revealed a close correlation (r = 0.961 and r = 0.882, respectively; P less than 0.001) despite dose adjustment. In marked hypochlorhydria documented by continuous pH monitoring, serum gastrin varied from normal up to profound hypergastrinaemia. These results demonstrate that the serum gastrin increase under powerful acid-inhibitory drug therapy depends upon a number of variables. (a) Only in patients with elevated gastrin levels, prior to omeprazole treatment, can moderate to marked hypergastrinaemia during omeprazole be expected. (b) Gastrin increases reached during the initial period of omeprazole treatment remain constant during long-term therapy. (c) Acid inhibition itself is not necessarily associated with an increase in serum gastrin in every patient, which suggests that the individual sensitivity of the gastrin cell to acid inhibition is more important for serum gastrin changes than the degree of acid inhibition itself.

Prospective evaluation of omeprazole treatment in reflux oesophagitis refractory to H2-receptor antagonists.

The efficacy of omeprazole therapy (40 mg daily) in H2-blocker refractory severe reflux oesophagitis (Grade II-IV; Savary and Miller classification) was investigated in 61 patients. Mean duration of reflux disease and preceding H2-antagonist treatment were 4.3 years and 15 months, respectively. Healing rates at 4, 8 and 12 weeks were 48%, 80% and 92%, respectively. There was a correlation between severity of oesophagitis and duration of omeprazole therapy necessary for healing. Three patients (5%) required higher dosages than 40 mg for healing. Symptomatic responses paralleled healing. It is concluded that omeprazole is a highly effective drug for severe reflux oesophagitis not responding to H2-blocker treatment and that 40 mg daily is the optimal dose.

One-year prophylactic efficacy and safety of pantoprazole in controlling gastro-oesophageal reflux symptoms in patients with healed reflux oesophagitis.

BACKGROUND: Pantoprazole is a benzimidazole derivative which selectively inhibits the proton pump H+. K+-ATPase necessary for the final step in gastric acid secretion. AIM: To investigate the tolerability and the prophylactic effect of pantoprazole 40 mg once daily on relapse in patients whose reflux oesophagitis had been healed. METHODS: The safety of pantoprazole 40 mg once daily was assessed in an open 1-year trial on 222 patients whose reflux oesophagitis had been healed with omeprazole or pantoprazole. Relapse was defined as endoscopically-confirmed reflux oesophagitis (at least Grade I), with endoscopies being performed for patients experiencing 3 consecutive days of disease-specific symptoms. RESULTS: Kaplan-Meier survival analysis at 6 and 12 months gave estimated treatment failure rates of 2% and 6% from confirmed relapses (per-protocol), and of 9% and 30% for a worst-case group (all withdrawals counted as failures). The only population shift in laboratory variables was a doubling of the median serum gastrin level over the first 6 months; thereafter it stabilized. Fifty-four (24%) patients experienced adverse events; 15 of these withdrew. Serious adverse events were reported for 12 patients. CONCLUSIONS: Pantoprazole appears to be highly effective and to have a good safety profile for long-term prophylaxis of reflux oesophagitis.

Eradication of Helicobacter pylori heals atrophic corpus gastritis caused by long-term treatment with omeprazole.

Long-term treatment with proton pump inhibitors in patients with Helicobacter pylori gastritis can lead to atrophic changes in the corpus mucosa. What is still unclear, however, is whether this atrophy can regress in response to Helicobacter pylori eradication. We report on a male patient with Helicobacter pylori gastritis receiving long-term treatment (4 years) with omeprazole for gastrooesophageal reflux disease, who developed autoaggressive gastritis with progressive atrophy, hypochlorhydria, hypergastrinaemia and nodular ECL-cell hyperplasia. To determine whether these changes might be induced to regress, Helicobacter pylori eradication therapy was administered. Ten months after Helicobacter pylori eradication autoaggressive lymphocytic infiltrates were no longer detectable, and the glands in the corpus mucosa had normalised despite continued treatment with omeprazole - a finding that was confirmed at two further follow-up surveys performed at 6-month intervals. This case report shows that atrophy of the corpus mucosa developing under long-term treatment with a proton pump inhibitor can be cured by eradicating Helicobacter pylori.

Serotoninergic control of somatostatin and gastrin release from the isolated rat stomach.

The influence of exogenous serotonin on the secretion of gastric somatostatin and gastrin was investigated under in vitro conditions using an isolated, vascularly perfused rat stomach preparation. Serotonin stimulated gastrin release, maximal effects were observed at 10(-6) M which increased gastrin levels by 78%; on the contrary, somatostatin secretion was inhibited (maximal inhibition of 56% at 10(-6) M). Changes in hormone secretion in response to serotonin were reversed by combined blockade of 5-HT1 and 5-HT2 receptors by methysergide and blockade of 5-HT2 receptors by ketanserin (10(-5) and 10(-6) M, respectively), and of cholinoreceptors by atropine (10(-5) M). It is concluded that in rats in vitro serotonin inhibits release of gastric somatostatin and stimulates gastrin secretion via specific serotonin receptors but muscarinic cholinergic receptors are also involved.

Effect of starvation on endocrine cells in the rat stomach.

The influence of food deprivation on gastric G- and D-cells and on parietal cells was studied in the rat. In fed controls and groups of rats fasted for 12 and 96 h G-, D- and parietal cell densities, somatostatin and gastrin concentration in antral and fundic specimens and serum gastrin were compared. Gastrin in antral mucosa, serum gastrin, G-cell density as well as antral D-cell density decreased in long-term fasted rats by 52%, 90%, 58% and 42%, respectively. Fundic D-cell density remained unchanged. After 96 h starvation somatostatin concentration slightly increased in antral mucosa (+35%; P less than 0.05), but decreased in fundic mucosa (-40%; P less than 0.05). Parietal cell density was not influenced by prolonged fasting. These findings demonstrate that changes in D-cell morphology and mucosal somatostatin content are not parallel and that the rat gastric D-cell is less dependent on food in the gastric lumen than the G-cell. The unaltered fundic D-cell density reflects the functional activity of gastric D-cell which has also been shown to be independent of the presence or absence of food.

Low hepatic clearance of peptide YY (PYY) in the perfused rat liver.

The hepatic clearance rate and secretion rate mainly determine peripheral plasma concentrations of regulatory peptides released from the gastrointestinal tract. In the present study hepatic extraction of peptide YY (PYY) during a single passage was investigated in the in situ perfused rat liver excluding modulating actions of circulating hormones. During perfusion of low amounts of PYY (50, 100, 500 pmol l-1), peptide concentrations in the portal vein (5.1 +/- 4.6, 98.1 +/- 2.6, 558 +/- 13.6 pmol l-1) and in the hepatic vein (50.2 +/- 1.4, 88.6 +/- 2.2, 503 +/- 18.1 pmol l-1 was only 22.1%. PYY had no influence on hepatic glucose and lactate production, portal flow as well as bile flow and bile acid secretion at these concentrations. PYY seems to traverse the liver almost intact and reaches the target organs without any significant hepatic extraction. Concomitant studies on metabolic and excretory functions of the liver showed no effect of PYY.

Role of cholecystokinin in the control of gastric somatostatin in the rat: in vivo and in vitro studies.

Cholecystokinin (CCK) has been shown to be a powerful stimulus for somatostatin release from isolated canine fundic D-cells in short-term culture. The influence of the CCK analogue caerulein on the secretory activity of the D-cell in the intact stomach in vitro and the effect of elevated plasma levels of endogenous CCK on gastric somatostatin stores in vivo were investigated in the rat. Basal somatostatin secretion from the isolated, vascularly perfused rat stomach preparation was not affected by various doses of caerulein. Slight stimulation of somatostatin-like immunoreactivity (SLI) release by epinephrine was significantly inhibited by caerulein, whereas caerulein did not alter half-maximal stimulation of SLI secretion by isoproterenol. Rats with chronically elevated plasma CCK levels induced by experimental exocrine pancreatic insufficiency did not show any change in tissue concentrations of SLI or in D-cell number, both in the antrum and corpus. These data suggest that CCK--in contrast to dogs--is not an important modulator of gastric somatostatin in the rat.