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Biomedical subjects

C Emde

Publications and source records attributed to C Emde.

At least 37 records · Page 2Linked to original sources

Recommendations for long-term oesophageal pH monitoring.

Ambulatory 24-h pH monitoring in the distal oesophagus represents a widely accepted tool in the diagnosis of gastro-oesophageal reflux disease. When this method was first established, most attention was drawn to the definition of normal oesophageal pH values; various studies correlated morphological findings in the distal oesophagus with the extent of gastro-oesophageal reflux. We have compared different reflux-related variables under different measuring conditions; reflux time (percentage of time with pH below 4) was found to be much more reliable than variables derived from the recognition of single reflux episodes. The special advantage of long-term ambulatory pH monitoring is, however, in our opinion, its capacity for identifying gastro-oesophageal reflux as the primary cause of chest pain in those patients whose oesophagus has an endoscopically normal appearance. For this purpose, it is vital that the recording system be equipped with a reliable event marker; the oesophageal origin is confirmed by detection of a high coincidence between pain attacks and reflux episodes. The evaluation software for ambulatory pH monitoring must therefore allow for diagrammatic display of a complete 24-h recording where the onset of pain attacks is visible within the pH curve.

Chest Pain

Basic principles of pH registration.

Normally, pH-sensitive electrodes are used for measuring the acidity of an aqueous solution. A second electrode is required as reference and can be integrated in the pH-sensitive electrode (combined electrode); separate reference electrodes must be used, however, when combined ones are not available. Types of electrodes are: glass, antimony, ISFET and polymeric membranes; only glass and antimony electrodes are commercially available. Different factors determine the accuracy of a pH measurement, the most important being: (1) electrical and mechanical properties of the electrodes; (2) ionic strength, temperature and background activity of the test solution; and (3) electrical properties of the pH amplifier and display. The highest accuracy of about 0.1 pH units can be obtained with the glass electrode; the error of measuring systems equipped with antimony electrodes does not normally exceed 0.5 pH units. It is important to define the required accuracy prior to measurement. If, for example, long-term oesophageal pH monitoring is performed in newborns or infants, the best compliance is achieved with the relatively small and flexible antimony electrode. If, on the other hand, the effect of an allegedly weak drug on gastric acidity is to be tested in a volunteer study, only glass electrodes will be appropriate.

Antimony

Effect of a slow-release formula of trimoprostil on intragastric acidity in healthy volunteers.

We investigated the effect of a slow-release formula of trimoprostil, a prostaglandin E2 analogue, at a dose of 3 mg b.d. on circadian intragastric acidity in nine healthy volunteers using ambulatory pH-metry in a placebo-controlled study. The effect of trimoprostil was long lasting (8 hours during the night). However, it lowered gastric pH on average only by 0.4 pH units. In four of the six women severe side-effects occurred in the form of abdominal cramping, metrorrhagia, and/or diarrhoea. These disadvantages may limit the clinical use of this drug.

Adult

Exponential function for calculating saturable enzyme kinetics.

Enzyme kinetics are usually described by the Michaelis-Menten equation, where the time-dependent decrease of substrate (-dS/dt) is a hyperbolic function of maximal velocity (Vmax), Michaelis constant (Km), and amount of substrate (S). Because the Michaelis-Menten function in its most general meaning requires an assumption of steady-state, it is less curvilinear than true enzyme kinetics. A saturation-type exponential function is more curvilinear than the hyperbolic function and more closely approximates enzyme kinetics: -dS/dt = Vmax [1 - exp(-S/Km)]. The mathematical representation of enzyme kinetics can be further improved by introducing a deceleration term (Vdec), to make the assumption of a steady state unnecessary. For the action of chymotrypsin on N-acetyltyrosylethylester, the Michaelis-Menten equation yields the following: Vmax = 3.74 mumol/min and Km = 833 mumol. According to decelerated enzyme kinetics, the values Vmax = 4.80 mumol/min, Vdec = 0.0118 mumol/min, and the association constant (Ka) = 0.00111/mumol are more nearly accurate for this reaction (where 1/Ka = 901 mumol approximately Km).

Chymotrypsin

Transfer of large data sets from biomedical research: proposal for a universal data header (UNIDAT 1.0).

A universal data header for computerized data transfer between different research centers has been developed and successfully tested. The structure of this data header allows for data interchange irrespective of the internal data representation of the processor used. The first 128 byte are used for description of data structure followed by dynamically allocated space for string variables, event data, and measured data. Test programs written in Turbopascal and C are available on floppy disk (formatted for MS-DOS or OS/9) from the authors upon request.

Information Systems

Lessons from prolonged gastric pH monitoring.

Intragastric pH monitoring has shown that the distribution of acidity within the stomach is not homogeneous. Not only is it affected by meals but it also has a circadian rhythm in which nocturnal pH falls to very acid levels in normal subjects. Although results of pH monitoring are highly reproducible within individuals, considerable inter-individual variation has been shown. Duodenal ulcer patients do not appear to possess the normal buffering reaction to meals, but their night-time acidity is within the normal range. In these patients, antacids and pirenzepine have a small acid-neutralizing effect in the stomach; cimetidine is less potent than ranitidine and famotidine. Clinicians can choose between a single dose of either ranitidine or famotidine in the evening with dinner and a twice-daily regimen.

Gastric Acid

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.

Adult

Reduction of gastric acidity with ranitidine or famotidine: early evening dosage is more effective than late evening dosage.

The antisecretory effect of a once daily dose of ranitidine and famotidine was examined after administration of the drugs either immediately after dinner or 3 h after dinner. A placebo-controlled multiple cross-over study was performed in 7 healthy ambulatory volunteers. They were given, on 6 separate days at least 1 week apart, either placebo, ranitidine 300 mg or famotidine 40 mg, either immediately after dinner or 3 h later. Breakfast, lunch and dinner were standardized. 24-Hour intragastric acidity was measured with a combined glass electrode. Duration of secretory inhibition by a drug was defined as the nighttime period between the first rise of pH above and the final fall below 3.5. This value represents the 95% upper confidence limit of nighttime pH values during placebo treatment. Secretory inhibition with early and late administration of ranitidine lasted for 10.7 and 7.3 h, respectively (p = 0.012). With famotidine it lasted for 10.1 and 7.1 h, respectively (p = 0.005). Gastric acidity after dinner was decreased by early but not late intake of ranitidine and famotidine. Thus, both ranitidine and famotidine were more effective when taken early, immediately after dinner, than when taken late in the evening. This observation might affect the mode of ulcer treatment with these drugs.

Adult

It is wise to prescribe NSAIDs with modern gastroprotective agents?

The administration of non-steroidal anti-inflammatory drugs (NSAIDs) leads to mucosal lesions in the upper gastrointestinal tract. Furthermore, NSAIDs increase the risk of ulcer bleeding and perforation, but the overall risk of fatal complications is relatively small (about 21 per one million prescriptions). Therefore, in asymptomatic patients, it is not justified to prescribe NSAIDs together with gastroprotective agents. The following recommendations can be given with respect to the management of peptic lesions in patients taking NSAIDs: (i) Fibre endoscopy should be performed even when there are relatively mild symptoms since mucosal lesions in rheumatic patients under NSAIDs produce minor or no symptoms. (ii) "Modern" NSAIDs might produce less gastric lesions than aspirin. (iii) Rheumatic patients with peptic disorders should be treated with an H2-antagonist. (iv) After complications such as ulcer bleeding or after rapid recurrence of peptic lesions, maintenance treatment with an H2-antagonist is advisable.

Anti-Inflammatory Agents, Non-Steroidal

Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs.

Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. In addition, it could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data presented may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells from histocompatible immunized donors.

Animals

[Continuous intragastric pH-metry].

Ambulatory intragastric pH-metry is a suitable method of assessing gastric acidity under conditions of normal daily life. A detailed profile of intragastric acidity is given which is a reproducible individual characteristic. There is a circadian rhythm of gastric acidity in which pH rises during the night and after meals. pH-metry was used to determine the effects of H2-antagonists and antacids, and the results are the basis for the clinical use of intragastric pH-metry.

Antacids

Three-day continuous drainage of pancreatic juice in the cortisone-treated conscious rat: analysis of enzyme activities and ultrastructural changes.

We have investigated the short-term effects of hydrocortisone (60 mg/kg per day) and placebo on basal and stimulated pancreatic secretion in the conscious rat. Volume and enzyme secretion were determined; fine structural changes were examined simultaneously. The pancreatic and bile ducts were cannulated separately; pancreatic juice was drained via an isolated fistula, and bile was recirculated into the duodenum. The application of hydrocortisone led to an almost complete inhibition of the secretory response of the exocrine pancreas when stimulated with 0.25 U secretin in combination with 5 X 10(-8) g caerulein per h. It strongly affected the secretion rates of volume, protein, lipase, chymotrypsin, trypsin and carboxypeptidase, whereas the secretion rate of alpha-amylase continued to show a slight increase after stimulation. After stimulation with secretin and caerulein, the hydrocortisone-treated animals showed a higher density of zymogen granules in the acinar cell and an increase in the number of autophagic vacuoles in comparison to the equally stimulated placebo-treated rats. It is concluded that the short-term inhibition of pancreatic secretion by hydrocortisone occurs largely as a result of an inhibition of cellular enzyme discharge.

Animals

Lack of adaptive changes in human pancreatic amylase and lipase secretion in response to high-carbohydrate, low-fat diet applied by a 10-day continuous intraduodenal infusion.

In order to investigate whether the human exocrine pancreas is capable of adapting to a diet with a high-carbohydrate, low-fat, and normal protein content, 10 healthy subjects were given a continuous intraduodenal infusion of such a dietary composition (8760 kJ in 2400 ml/day) via a portable infusion pump over a period of 10 days. The diet consisted of 76% of calories as carbohydrates (80% oligosaccharides, 20% mono- and disaccharides), 10% as fat (more than 90% C18 fatty acids) and 14% as protein (oligo- and polypeptides; 11.8 g nitrogen per day). A complete pancreozymin-secretin test was carried out before and after the experimental period. The results show that the above dietary regimen leads to a significant (P less than 0.05) increase in the stimulated secretion rates of trypsin and chymotrypsin, whereas, in contrast to the findings in animal experiments, no change could be measured in the secretion rates of amylase and lipase.

Adaptation, Physiological