Clinical consequences of controversies in gastric physiology

Abstract

Studies on the regulation of gastric acid secretion started more than 100 years ago at an early phase of experimental physiology. In nearly the whole last century there were disputes about the interpretation of the findings: the interaction between the three principle gastric acid secretagogues acetylcholine, gastrin and histamine, the cell producing the relevant histamine which turned out to be the ECL cell, the ability of the ECL cell to divide and thus develop into tumours, the classification of gastric carcinomas and the mechanism for Helicobacter pylori carcinogenesis. The elucidation of the central role of the ECL cell and thus its main regulator, gastrin, solve all these controversies, and gives a solid base for handling upper gastrointestinal diseases.     

Chronic pancreatitis and extrapancreatic cancer A retrospective study among 181 patients with chronic pancreatitis

Summary The relationship between chronic pancreatitis (CP) and extrapancreatic cancer has been debated in the recent years. In prospective studies, it has been found that pancreatic cancer develops in 0–5% of patients with chronic pancreatitis. Many papers describe an increased relative risk for developing extrapancreatic cancer in patients suffering from chronic pancreatitis. In this study including 181 patients with CP, we found 14 patients with extrapancreatic cancer (three of these had two different types of cancer). No patient had pancreatic cancer. It was found that the respiratory airways and upper gastrointestinal tract were the dominating locations (five and four cases, respectively), but also genital and hemolymphopoietic cancers were represented (four and two cases, respectively). Two patients had metastatic cancer with unknown primary tumor. The patients with cancer tended to be older than those without cancer. The patients with CP had a 2.43 times greater risk of developing cancer than the general Danish population (age and sex standardized comparison). The relatively large number of cancers in the upper gastrointestinal tract and respiratory airways suggest that tobacco and alcohol may be responsible, as these organs have the highest exposure to these compounds, which are well known carcinogens.     

875 Cases of bacterial meningitis: Diagnostic procedures and the impact of preadmission antibiotic therapy Part III of a three-part series

Data on the bacteriological findings, diagnostic measures and clinical course of 875 patients with bacterial meningitis are presented. Findings from the medical records and from a follow-up questionnaire survey of 667 of these cases revealed no significant difference between patients treated with antibiotics before admission (pretreated) and those who were not treated before admission (non-pretreated) with respect to clinical condition on admission, mortality and late sequelae. Pretreatment was, however, associated with a longer duration of symptoms. Apart from cases due to Neisseria meningitidis, there were no significant differences in diagnostic findings between pretreated and non-pretreated cases. In the group of pretreated meningococcal patients, however, positive blood cultures, pleiocytosis in the cerebrospinal fluid (CSF) and positive cultures from sites other than blood and CSF were less frequent than in the non-pretreated cases.     

Orale Thrombozytenhemmung in der primären und sekundären Prävention

Cardiovascular disease is the leading cause of death in western societies, with further increasing incidence. Therefore both, primary and secondary prevention play a pivotal role. Medicamentous prevention schemes include the antithrombotic drugs acetylsalicylic acid (ASS) and clopidogrel. A number of studies tested the efficacy and safety of ASS for primary prevention. A meta-analysis of these primary prevention trials could demonstrate a decrease of cardiovascular events only for patients being at high cardiovascular risk. However, since ASS does not influence the mortality but is significantly increasing the risk for bleeding, careful risk stratification is indispensable prior to preventive chronic administration of the drug. Therapy with ASS in the secondary prevention is commonly accepted and clearly evidence-based given that a meta-analysis of 145 trials could demonstrate a significant decrease in mortality. A daily dose of 100 mg has been shown to achieve sufficient antithrombotic effects with an acceptable rate of side effects. Clopidogrel is currently not used for primary prevention, since evidence is lacking and the costs are high. For secondary prevention after acute coronary syndromes, a decrease of cardiovascular events could be demonstrated for clopidogrel. This benefit was especially pronounced after percutaneous coronary interventions. However, clopidogrel could not decrease the mortality. Therefore, long-term treatment with clopidogrel in the secondary prevention should be based on a critical appraisal of risk and benefit on the one hand and socioeconomic aspects on the other hand.     

Assessing the spatiotemporal evolution of neuronal activation with single-trial event-related potentials and functional MRI

The brain acts as an integrated information processing system, which methods in cognitive neuroscience have so far depicted in a fragmented fashion. Here, we propose a simple and robust way to integrate functional MRI (fMRI) with single trial event-related potentials (ERP) to provide a more complete spatiotemporal characterization of evoked responses in the human brain. The idea behind the approach is to find brain regions whose fMRI responses can be predicted by paradigm-induced amplitude modulations of simultaneously acquired single trial ERPs. The method was used to study a variant of a two-stimulus auditory target detection (odd-ball) paradigm that manipulated predictability through alternations of stimulus sequences with random or regular target-to-target intervals. In addition to electrophysiologic and hemodynamic evoked responses to auditory targets per se, single-trial modulations were expressed during the latencies of the P2 (170-ms), N2 (200-ms), and P3 (320-ms) components and predicted spatially separated fMRI activation patterns. These spatiotemporal matches, i.e., the prediction of hemodynamic activation by time-variant information from single trial ERPs, permit inferences about regional responses using fMRI with the temporal resolution provided by electrophysiology.     

Developing research priorities for nurses working in the gynaecology setting in Western Australia

Background

Nurses working in clinical settings are instrumental to translating research into practice. The Delphi approach has been used by clinicians worldwide to set research agendas relevant to their clinical work.

R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in Alcohol-Preferring Rats

(±)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (±)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long–Evans rats. As Long–Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long–Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine''s effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans.     

One-year follow-up study of patients with enterochromaffin-like cell carcinoids after treatment with octreotide long-acting release

OBJECTIVE: In a one-year study of 5 patients with chronic atrophic gastritis (CAG), pernicious anaemia (PA), hypergastrinaemia and enterochromaffin-like (ECL) cell tumours, the somatostatin analogue octreotide LAR (long-acting release) in a dose of 20 mg given intramuscularly at monthly intervals had an antiproliferative effect on the ECL cells. The aim of the present study was to follow neuroendocrine (NE) markers in the blood and macroscopic and histopathological changes in the stomach during a 12-month follow-up after discontinuation of octreotide LAR treatment. MATERIAL AND METHODS: Five patients underwent upper gastrointestinal endoscopy at 6 and 12 months' follow-up after octreotide LAR treatment. Biopsies from flat, oxyntic mucosa and from tumours were obtained. Sections were stained with haematoxylin-erythrosin and immunostained for the NE cell marker chromogranin A (CgA). Serum gastrin and CgA were measured every 3 months. RESULTS: The number of visible tumours was unchanged (7) at 12 months' follow-up. One lesion showed carcinoid tumour and the others various degrees of linear and micronodular NE hyperplasia. At the same time-point, biopsies from flat, oxyntic mucosa showed a slightly (non-significant) elevated number of CgA immunoreactive (IR) cells. Serum gastrin increased from 186+/-50 pM (mean+/-SEM) to 603+/-109 pM (normal < 40 pM); p<0.05, and serum CgA increased non-significantly from 25+/-2 ng/ml (normal < 30 ng/ml) to 61+/-11 ng/ml. CONCLUSIONS: During follow-up, slightly elevated levels of serum CgA and CgA IR cells in the oxyntic mucosa, without significant recurrence of ECL cell carcinoids, were observed.