Claus J. Fimmel

Long-term ambulatory gastric pH monitoring: Validation of a new method and effect of H2-antagonists

A new ambulatory monitoring system was evaluated for long-term measurements of gastric acidity. A close correlation was observed between values indicated by the pH electrode of the system and the pH of simultaneously aspirated gastric juice, suggesting that the electrode signaled the pH of the gastric fluid content. When the pH electrode was passed via an endoscope, and its bulb was placed against the corpus mucosa, a higher acidity was recorded as compared with gastric juice. To test whether the electrodes measured mucosal pH during ordinary test conditions, the readings of pH probes with mechanically shielded bulbs that did not come into direct contact with the mucosa were compared with those of nonshielded probes in identical positions. Similar results were observed, supporting the hypothesis that nonshielded probes measured the pH of gastric contents rather than that of the mucosa. The importance of a standardized electrode position and a fixed meal schedule was demonstrated in simultaneous recordings of antral and fundic pH. Under fasting conditions, acidity was similar in both regions. After ingestion of a meal, gastric contents were more alkaline in the fundus than in the antrum. A wide range of 24-h acidity (19-83 mmol/L) was detected in 25 healthy subjects. The day-to-day reproducibility of the method as revealed in two consecutive 24-h tests was good. The effect of cimetidine and ranitidine on gastric acidity was evaluated in 9 subjects in a double-blind, double-dummy trial. Mean 24-h H+ activity was 37.4 +/- 4.6 mmol/L under placebo medication. It was lower with cimetidine, two doses of 400 mg (23.8 +/- 4.0); cimetidine, four doses of 400 mg (10.2 +/- 3.0); ranitidine, two doses of 150 mg (10.3 +/- 3.6), and two doses of 300 mg (10.0 +/- 3.5), respectively. In conclusion, ambulatory long-term pH monitoring is a suitable method to assess the physiologic pattern of gastric acidity and the effect of antisecretory drugs.

Effect of Gastric and Transpyloric Tubes on Gastric Emptying and Duodenogastric Reflux

The effect of thin and pliable gastric and transpyloric duodenal tubes on gastric emptying was studied in healthy volunteers. Gastric emptying was unaffected by both gastric and transpyloric tubes. Gastric emptying was also similar whether a milk-cream meal was instilled via a tube or was swallowed. The effect of a transpyloric tube on postprandial and fasting duodenogastric reflux was studied by using a technique that does not require a transpyloric tube in order to measure reflux. Duodenogastric reflux was similar in the fasting state and after feeding and was not affected by a transpyloric tube. In conclusion, thin and pliable gastric and transpyloric tubes do not affect gastric emptying and duodenogastric reflux in humans, and, in addition, the mode of administration of a meal does not affect gastric emptying.

Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man?

The interaction between smoking and the effect of histamine H2-antagonists on intragastric acidity was examined in a double blind double dummy placebo controlled study. Healthy volunteers, 11 smokers and 10 non-smokers, were given, on four separate days at least one week apart, either placebo or cimetidine 800 mg nocte or ranitidine 2 X 150 mg per day or ranitidine 300 mg nocte. Tablets were taken at 2115 and 0900 h. Smokers smoked a cigarette hourly from 0700 to 2300 h. Breakfast, lunch, and dinner were standardised. Intragastric acidity was measured with a combined intragastric glass electrode and a solid state recorder. The subjects were fully ambulatory. The three histamine H2-receptor antagonist regimens were less effective (p = 0.04) in smokers than in non-smokers, but the difference between acidity of smokers and non-smokers was small. Means of medians of pH during a 24-h period with placebo, cimetidine 800 mg, ranitidine 2 X 150 mg and ranitidine 300 mg were 1.6, 2.3, 3.1, and 2.7 in smokers and 1.5, 2.7, 3.2, and 3.1 in non-smokers, respectively. In a second part of the study seven chronic smokers were reexamined after acutely stopping smoking: inhibition of gastric acidity by histamine H2-receptor antagonists was similar before and after withdrawal. Smoking does not affect intragastric acidity in untreated volunteers and only slightly decreases the effectiveness of histamine H2-receptor antagonists on intragastric acidity. This effect best in part explains the unfavourable effect of smoking on healing of peptic ulcer in patients treated with these drugs.

Stimulation of gastric acid secretion increases mucosal blood flow in immediate vicinity of parietal cells in baboons

In acute experiments carried out in 27 baboons under general anesthesia, the regional gastric mucosal and muscle layer blood flow and gastric acid secretion were measured during 4 hr. Baboons were allocated to each of the following six groups: control, gastric acid stimulation with histamine 40 Μg/kg/hr intravenous, inhibition of basal or stimulated acid secretion with either ranitidine 50 mg intravenous or omeprazole 1 Μg/kg/hr. There were no significant cardiovascular alterations during the experiments. Histamine stimulation produced a concomitant rise in acid secretion and increase in blood flow only to the mucosal layer of the parietal-cell-bearing area of the stomach. Neither the underlying muscle layer nor the non-parietal-cell-bearing fundic or antral mucosa took part in this response, suggesting that a mechanism controlling blood flow is present in close proximity to the parietal cells. It was also established that the increase in blood flow occurs in response to parietal cell activity and not as a result of the action of histamine on the vascular system. Suppression of both basal and stimulated acid secretion did not cause a fall of mucosal blood flow below basal levels in any part of the stomach, indicating that drugs that inhibit parietal cell activity can be used in conditions where gastric mucosal ischemia should be avoided.

Is There a Relationship between Gastric Mucosal Blood Flow and Stress Lesions in Hemorrhagic Shock

The relationship between gastric mucosal blood flow and stress lesion formation during hemorrhagic shock was studied in anesthetized dogs. Shock was induced by graded arterial bleeding. Blood flow was measured by means of the radioactive microsphere technique. Mapping of blood flow was achieved by measuring the microsphere accumulation in mucosal and muscle segments of 1-2 cm side length of the entire stomach. To produce a varying incidence of lesions the metabolic acidosis of shock was either fully corrected by intravenous sodium bicarbonate (n = 5), partially corrected (n = 4) or left uncorrected (n = 3). Mucosal lesions developed more frequently in dogs without correction than in dogs with partial correction or full correction. In 4 dogs not subjected to shock, no mucosal lesions were observed at the end of the experiments. Mucosal blood flow varied from segment to segment by a factor of up to 20, but individual segments tended to maintain their relative flow values during shock. Correction of metabolic acidosis did not significantly affect blood flow. Likewise, flow was similar in segments with and without lesions. Therefore, low regional blood flow did not predispose to the development of lesions and high flow did not prevent them. We conclude that focal mucosal ischemia alone does not lead to stress lesion formation during hemorrhagic shock.

Utility of electronic medical recordbased fibrosis scores in predicting advanced cirrhosis in patients with hepatitic C virus infection

Abstract Objective To determine whether advanced cirrhosis - defined by the detection of nodular liver contours or portal venous collaterals on imaging studies - could be predicted by fibrosis algorithms, calculated using laboratory and demographic features extracted from patients’ electronic medical records. To this end, we compared seven EMR-based fibrosis scores with liver imaging studies in a cohort of HCV patients. Methods A search of our health system’s patient data warehouse identified 867 patients with chronic HCV infection. A total of 565 patients had undergone at least one liver imaging study and had no confounding medical condition affecting the imaging features or fibrosis scores. Demographic and laboratory data were used to calculate APRI, Fib4, Fibrosis Index, Forns, GUCI, Lok Index and Vira-HepC scores for all viremic patients who had undergone liver imaging. Data points selected for the calculation of these scores were based on laboratory results obtained within the shortest possible time from the imaging study. Areas under the receiver operating curves (AUROC), optimum cut-offs, sensitivities, specificities and positive and negative predictive values were calculated for each score. Results Seven algorithms were performed similarly in predicting cirrhosis. Sensitivities ranged from 0.65 to 1.00, specificities from 0.67 to 0.90, positive predictive values from 0.33 to 0.38, and negative predictive values from 0.93 to 1.00. No individual test was superior, as the confidence intervals of all AUROCs overlapped. Conclusions EMR-based scoring systems performed relatively well in ruling out advanced, radiologically-defined cirrhosis. However, their moderate sensitivity and positive predictive values limit their reliability for EMR-based diagnosis.

Hepatitis C screening in commercially insured U.S. birth-cohort patients: Factors associated with testing and effect of an EMR-based screening alert

Abstract Background and Objectives Hepatitis C virus (HCV) testing rates among U.S. birth-cohort patients have been studied extensively, limited data exists to differentiate birth-cohort screening from risk- or liver disease-based testing. This study aims to identify factors associated with HCV antibody (HCV-Ab) testing in a group of insured birth cohort patients, to determine true birth cohort testing rates, and to determine whether an electronic medical record (EMR)-driven Best Practice Alert (BPA) would improve birth cohort testing rates. Methods All birth-cohort outpatients between 2010 and 2015 were identified. HCV-Ab test results, clinical, and demographic variables were extracted from the EMR, and factors associated with testing were analyzed by logistic regression. True birth-cohort HCV screening rates were determined by detailed chart review for all outpatient visits during one calendar month. An automated Best Practice Alert was used to identify unscreened patients at the point of care, and to prompt HCV testing. Screening rates before and after system-wide implementation of the BPA were compared. Results The historic HCV-Ab testing rate was 11.2% (11,976/106,753). Younger age, female gender, and African American, Asian, or Hispanic ethnicity, and medical comorbidities such as chronic hemodialysis, HIV infection, and rheumatologic and psychiatric comorbidities were associated with higher testing rates. However, during the one-month sampling period, true age cohort-based testing was performed in only 69/10,089 patients (0.68%). Following the system-wide implementation of the HCV BPA, testing rates increased from 0.68% to 10.76% (P<0.0001). Conclusions We documented low HCV-Ab testing rates in our baby boomers population. HCV testing was typically performed in the presence of known risk factors or established liver disease. The implementation of an EMR-based HCV BPA resulted in a marked increase in testing rates. Our study highlights current HCV screening gaps, and the utility of the EMR to improve screening rates and population health.

Relapse of HCV Genotype 1b Infection After Sofosbuvir/Ledipasvir Treatment Presenting as De Novo Cryoglobulinemic Vasculitis

Relapse of hepatitis C virus (HCV) genotype 1 infection after combination therapy with sofosbuvir and ledipasvir is unusual. We report a treatment-naïve, non-cirrhotic patient in whom the relapse of genotype 1b HCV infection was accompanied by de novo cryoglobulinemic vasculitis and glomerulonephritis, requiring hemodialysis for acute renal failure. Sequence analysis revealed several resistance-associated variants in the HCV NS5a gene but not in NS3/4A. The patient’s vasculitis was successfully treated with immunosuppression and plasmapheresis, followed by retreatment of HCV with a combination of sofosbuvir, simeprevir, and ribavirin. The patient achieved sustained virological response, recovered his renal function, and remains in remission from cryoglobulinemia.

Induction of Anacidity Restores Gastric Aminopyrine Clearance in Canine Hemorrhagic Shock

The determinants of gastric aminopyrine clearance were studied in a canine hemorrhagic shock model. Adult mongrel dogs were anesthetized, and their stomachs perfused with 0.1 N HCl through an esophageal and a duodenal cannula. Blood flow to the serosal layer of the anterior gastric wall was measured by a laser flowmeter. Hemorrhagic shock was induced by controlled arterial bleeding to a mean systolic blood pressure of 40 +/- 5 mm Hg (n = 8), resulting in a 36 +/- 8% drop of gastric wall blood flow. In contrast, the aminopyrine clearance did not reveal the expected drop and remained unchanged during shock. When acid secretion was abolished by intravenous omeprazole (1.3 mg/kg bolus plus 0.75 mg/kg/h infusion), aminopyrine concentrations dropped in the gastric perfusate and rose in the serum during shock, resulting in a similar decrease in the clearance (53 +/- 25%) as compared to the flowmeter readings. In control experiments without hemorrhagic shock, omeprazole did not affect the concentrations of aminopyrine in serum and in the perfusate, or the recovery of 14C-labeled aminopyrine in the mucosa at the end of the experiment. These studies indicate that the aminopyrine clearance is impaired in hemorrhagic shock, and that complete inhibition of acid secretion by omeprazole restores the apparent aminopyrine clearance by divergent effects on blood and gastric juice concentrations of aminopyrine.