Measuring the influence of aerosols and albedo on sky polarization.

All-sky distributions of the polarized radiance are measured using an automated fish-eye camera system with a rotating polarizer. For a large range of aerosol and surface albedo situations, the influence on the degree of polarization and sky radiance is investigated. The range of aerosol optical depth and albedo is 0.05-0.5 and 0.1-0.75, respectively. For this range of parameters, a reduction of the degree of polarization from about 0.7 to 0.4 was observed. The analysis is done for 90° scattering angle in the principal plane under clear sky conditions for a broadband channel of 450 ± 25 nm and solar zenith angles between 55° and 60°. Radiative transfer calculations considering three different aerosol mixtures are performed and and agree with the measurements within the statistical error.

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.

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.

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.

Early evening nizatidine intake with a meal optimizes the antisecretory effect.

The importance of the temporal relationship between meal and nizatidine intake was studied in a six-armed, double-blind, placebo-controlled trial. Eleven healthy volunteers received early (18.00 hours) or late (21.00 hours) supper, with either placebo, early (18.00 hours) nizatidine, or late (21.00 hours) 300 mg nizatidine. Ambulatory 21-hour gastric pH-metry was performed and plasma nizatidine concentrations were determined by high pressure liquid chromatography. Early-nizatidine/early-supper (median pH 2.50), but not late-nizatidine/late supper (median pH 2.30), produced significantly higher median 21-hour pH values than did early-nizatidine/late-supper (median pH 1.90). Concomitant food delayed the absorption of nizatidine but did not change the drug's bioavailability. Oral nizatidine should be taken with food, preferably early in the evening, to optimize its anti-secretory effect.

Effect of the somatostatin analog octreotide on gastric mucosal function and histology during 3 months of preoperative treatment in patients with acromegaly.

OBJECTIVE: To study the effects of the somatostatin analog octreotide on gastric mucosal function and histology during short-term (3 months) preoperative treatment in patients with acromegaly. DESIGN: Open design clinical study. METHODS: 10 patients were studied before treatment with octreotide (pre-tx), on day 1 of 300 microg octreotide/day (d300), after 1 week on 300 (w300), 600 (w600) or 1500 (wl500) microg octreotide/day, and after an additional 2.5 months on 1500 microg octreotide/day (M3). An 8h gastrin profile was obtained and ambulatory intragastric 23h pH-metry carried out at the indicated time points. Gastroscopy was performed at pre-tx and M3 and multiple mucosal biopsy specimens taken. RESULTS: The mean serum gastrin concentration at first declined during octreotide therapy to a nadir at w1500, then recovered despite ongoing therapy (probably in response to reduced gastric acidity) and was similar to pre-tx values at M3 (mean+/-S.E.: 87+/-26, 50+/-11 and 98+/-46ng/l for pre-tx, w1500 and M3 respectively; P<0.05, pre-tx vs w1500). Gastric acidity had also declined at d300(P<0.05, d300 vs pre-tx), then recovered (despite the increase in the octreotide dose), but declined again at M3 (mean pH (95% confidence interval): 2.4 (1.7-3.2), 3.3 (2.4-4.3), 2.6 (1.8-:3.5, n=8) and 2.9 (1.6-4.2, n=7) at pre-tx, d300, w1500 and M3 respectively). The gastrin concentration at M3, although similar to pre-tx values, remained inadequately low for the reduced gastric acidity. The reduction in gastric acidity was marked during the daytime (0900-2200 h; P<0.01, d300 vs pre-tx and P=0.028, M3 vs pre-tx). However, while the stimulated postprandial gastric acid secretion was reduced at d300 (P<0.01, d300 vs pre-tx) and at M3 (n=7; P=0.027, M3 vs pre-tx), fasting and preprandial acidity was not affected. During the night, gastric acidity was reduced from 2200 to 0300 h, but the reduction was less marked than during the daytime. Paradoxically, the physiological intermittent late nocturnal reduction in acidity ('pH peaks' (0300-0800 h)) was abolished rather than enhanced. No patient acquired new Helicobacter pylori infection. The mean gastritis scores for antrum and body (n=8, Sidney classification) increased marginally from 1.7 to 1.9 (chronicity) and from 0.7 to 0.9 (atrophy), while the activity score was slightly reduced from 1.2 to 1.0. CONCLUSIONS: Three months of preoperative octreotide treatment profoundly and persistently altered gastric mucosal function (gastrin suppression, reduced acidity), but caused only minor variations in the pre-existing gastritis scores.

Reduction of 24-hour gastric acidity by different dietary regimens: a randomized controlled study in healthy volunteers.

Evidence from animal experiments suggests that intraduodenal infusion of nutrients leads to an inhibition of gastric acid secretion via an enterogastric feedback mechanism. Detailed data are lacking, however, on the difference in circadian gastric acidity between gastric and intraduodenal alimentation in man. We conducted a randomized study in 10 healthy volunteers (5 men, 5 women, age 22-30 yr). From 8:00 am of the first study day until 4:00 pm of the next day, either a standardized normal meal or a liquid polymer diet (Fresubin) was given orally at 8:00 am, noon, and 6:00 pm. In a third experiment, a liquid hydrolysed diet (Survimed OPD) was continuously applied to the duodenum using a portable pump. Daily caloric intake and main nutrient components were comparable in all three diets. From 2:00 pm of the first day until 4:00 pm of the next day, an intragastric pH-metry was performed with a combined glass pH-electrode in the gastric corpus. Median pH-values from predefined time periods (whole day, prandial, interdigestive, nocturnal) were compared between the three groups. The orally applied liquid polymer diet led to a significantly stronger increase in 24-hr and prandial gastric pH than the normal diet. Twenty-four-hr, interdigestive, and nocturnal pH-median values were significantly higher during continuous intraduodenal application of the liquid hydrolysed diet than during the normal diet.

Subjective distress during continuous enteral alimentation: superiority of silicone rubber to polyurethane.

A small-bore feeding tube of silicone rubber was developed in order to improve the acceptance of enteral feeding. The insertion procedure was facilitated by providing a double guidewire which allows continuous adjustment of tip rigidity. The usefulness of this tube was tested in a short-term and a long-term volunteer study as well as in a prospective follow-up of patients receiving enteral nutrition. The volunteer study showed that the newly developed tube significantly reduced subjective distress (rank value 14) when compared to a conventional tube made of polyurethane (rank value 20). In the patient study, 131 silicone rubber tubes were used in 85 patients who received enteral nutrition for a total period of 2080 days and complained about foreign-body feeling and rhinorrhea in only 3.7% and 0.5% of the days, respectively. The rate of inadvertent removals was relatively low (32%), mainly due to restricted mental status of the patients.

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.

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.

Diagnostic assessment of gastroesophageal reflux disease: what is possible vs. what is practical?

The diagnosis of gastroesophageal reflux disease (GERD) entails the identification of patients with esophagitis and its complications as well as patients who have symptoms but no mucosal disease. Endoscopy is mandatory to establish a diagnosis of reflux esophagitis, to exclude other esophageal disease and to permit directed biopsy if columnar metaplasia, dysplasia or carcinoma is suspected. The lesions of reflux esophagitis--erosions, ulceration, stricturing and metaplasia--should be identified and graded independently, using a classification system such as the recently described "MUSE" (Metaplasia, Ulcer, Stricture, Erosions) system. Fluoroscopy can identify associated structural changes such as stricturing or esophageal shortening. Measures of esophageal acid exposure time may be used to quantify reflux before and after treatment; however, if the patient has typical symptoms but no esophagitis, a temporal association between symptoms and episodes of esophageal acidification should be sought. Ambulatory 24-hour esophageal pH-monitoring with accurate event-marking provides recordings suitable for an objective statistical analysis, which was evaluated prospectively in 14 patients. Computerized analysis of 24-hour esophageal pH recordings diagnosed 5 patients as having acid-related symptoms although only 3 of 5 patients fulfilling the criteria for pathological reflux had pH-related chest pain. This finding was confirmed by 5 experts who analyzed all recordings visually, unaware of the result of the computer analysis. The Bernstein test should be reserved for patients whose symptoms are too infrequent to permit an objective assessment of symptom occurrence during pH monitoring. In conclusion, i) endoscopy is the test of choice for the diagnosis of esophagitis but it should be supplemented by a standardized and reliable scoring system for disease severity; ii) ambulatory esophageal pH recording with accurate event-marking is the test of choice for the diagnosis of GER-related symptoms, but it should be supplemented by an objective assessment of the temporal relationship between symptoms and esophageal pH; and iii) esophageal manometry is the test of choice for evaluating esophageal peristalsis and LES (lower esophageal sphincter) function but, in the context of GERD, its main indication is the assessment of GERD patients who are being considered for surgery. The widespread use of other tests for clinical purposes must await a better understanding of the pathophysiological mechanisms which can lead to the development of GERD.

[The effect of a calcium carbonate-bismuth subsalicylate combination on intragastric acidity over the course of 24 hours. A randomized study of healthy probands]. / Die Auswirkung einer Calciumcarbonat-Wismutsubsalicylat-Kombination auf die intragastrale Acidität im 24-Stunden-Verlauf. Eine randomisierte Studie bei gesunden Versuchspersonen.

Bismuth salts are successfully used for the treatment of campylobacter-pylori-associated gastritis. It cannot be excluded, however, that calcium carbonate, which is present in one of the recommended preparations (calcium carbonate/bismuth subsalicylate, Jatrox), may have an additional therapeutic effect due to an increase of intragastric pH. Therefore, the in-vitro H+ buffering capacity of Jatrox was determined in comparison to other antacids using the pH-stat technique, and its effect on intragastric acidity was tested in 15 healthy volunteers using ambulatory 24-hour pH-metry (combined glass electrode in gastric corpus, solid state memory recorder, sampling rate 30/min). At two study sessions, the volunteers received standardized normal meals (8:00 a.m., 12:00 noon, 6:00 p.m.) and, in randomized order, either Jatrox (three times 2 tablets one hour before meals) or no medication. Under in-vitro conditions, the buffering capacity of Jatrox amounts to 7.82 mmol H+ per tablet (equivalent to 47 mmol H+/24 h at recommended dosage), which is relatively low. Under in-vivo conditions, gastric pH only increases significantly during the first hour after medication. This short-lasting effect, however, has no influence on the 24-hour median pH. It is concluded from these results that the calcium carbonate contained in Jatrox probably does not contribute directly towards its therapeutic effect in promoting the healing of gastritis.

[Lymphedema--treatment]. / Erfolgreich entstauen durch kombinierte Therapie.

Treatment of lymphedema utilizes complex physical (or decongestive) therapy (CDT), so-called. This covers a number of measures including compression, lymph drainage, skin care and individualized exercises. CDT is divided into two phases--an intensive phase during which daily treatment is applied over a period of two to four weeks, and a maintenance phase in which especially compression therapy is continued in order to secure the positive effects achieved during the first phase. Treatment should be initiated in an early stage of the condition, and the aim is to return the patient to the symptom-free latency stage. Neither isolated manual lymph drainage nor equipment-based decongestion is considered for the treatment of lymphedema. To date, the efficacy of various drugs, including selenium, has not been confirmed.

Electrochemical aspects of pH electrodes.

When a pH electrode is applied intragastrically for long-term pH metry, problems may occur which are related to the specific conditions of gastric juice and to the possible difference between the temperature of buffer solutions and the body temperature. The fact that pH electrodes measure the activity of the hydrogen ion instead of its concentration may, in concentrated solutions (i.e. pH less than 2), lead to an error that is even compounded if other ions are present in high concentrations. This error normally does not influence comparisons between measurements obtained under the same conditions. It is, however, important to check which correction procedures are provided for the particular devices being used when comparing results obtained by different research groups. Calibration of the electrode at a temperature differing from body temperature may result in an important error. Complete correction for this error may be achieved for glass electrodes by a modified version of the Nernst equation; for monocrystalline antimony electrodes an empirically derived formula is available allowing for partial correction. In general, all types of electrodes should be calibrated using two different buffer solutions (one with a pH value between 6 and 8 and another with a pH of 2 or less) and the double-point interpolation method.

Graphical display and statistical evaluation of data gained by long-term ambulatory intragastric pH monitoring.

The graphical display of data gained by long-term ambulatory intragastric pH monitoring requires different methods to present (1) the circadian time course of each individual, (2) data from all individuals belonging to the same group, and (3) data from two or more groups in a summary plot. Data reduction is normally required in all three cases; for this purpose, it is advisable to use median values from consecutive time periods, e.g. of 10-20 min each. All data from a total group of comparable individuals may be displayed using a pseudo-3D-graph allowing for easy recognition of interindividual variability. Summary curves from all data of one group may be gained by calculating medians from time-equivalent pH values and plotted together in one graph. The study design should take into consideration that intraindividual reproducibility of intragastric pH metry is excellent, while large variations may occur between individuals. Therefore, repeated measurements in the same individual under the different conditions to be tested are highly recommended. If two measurements are performed in each individual, the data are statistically evaluated using Wilcoxon paired rank test; Friedman rank test and subsequent multiple comparison according to Wilcoxon-Wilcox are proposed in the case of more than two groups. Alternatively, multiple single tests may be used; this procedure, however, requires appropriate correction of the alpha-error which is best done using the exact versions of the test.

Early changes in brush border disaccharidase kinetics in rat jejunum following subcutaneous administration of tetraiodothyronine: a quantitative histochemical study on villi revealing normal morphology.

In order to test the influence of thyroid hormones on small intestine function, adult female Wistar rats were injected daily with either 100 microgram/100 g body weight tetraiodothyronine or placebo. After 12 days, jejunal segments were removed and processed for morphometric analysis of mucosal architecture and quantitative histochemical determinations of the apparent Km- and Vmax-values of lactase/beta-glucosidase and neutral alpha-glucosidase at constant basal and apical measuring positions along the villi. The villus-crypt-architecture was the same in both experimental groups. At the cellular level, however, application of tetraiodothyronine resulted in a marked decrease in the apparent Vmax of lactase/beta-glucosidase at both villus positions, maintaining the normal activity gradient along the villi. In comparison with the controls, a less pronounced but significant reduction in activity was also demonstrated for the neutral alpha-glucosidase. Substrate affinity, however, was only increased for this enzyme, the apparent Km of lactase/beta-glucosidase not being affected by the hormone. The results indicate a direct effect of tetraiodothyronine on jejunal brush border disaccharidases of the rat. The alternative mechanism, an effect mediated by an altered enterocyte turnover is unlikely to occur.

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).

Exponential function of chymotrypsin action.

Enzyme kinetics are usually described by the hyperbolic Michaelis-Menten equation, but they can also be described by the following exponential function: -dS/dt = Vm [1 - exp (-S/Km)]. The time-dependent decrease of the substrate (-dS/dt) is an exponential function of maximal velocity (Vm), the Michaelis constant (Km) and the actual substrate value (S). This exponential function is based on the assumption that the association of the substrate-enzyme complex is a concentration-dependent process, whereas the transformation of the substrate-enzyme complex is time-dependent. It can be shown that this exponential function is a more general solution of which the hyperbolic Michaelis-Menten equation is a special derivative under the conditions of low substrate (S) and high constant (Km) values. If the association process is time-dependent, the decline in substrate values will show a more concave curve. However, exponential functions in general are more concave than hyperbolic functions. Probably, therefore, the enzyme action of chymotrypsin could be described more appropriately by the present exponential function than by the conventional hyperbolic function.