A novel tablet-based 13C urea breath test for Helicobacter pylori with enhanced performance during acid suppression therapy.

BACKGROUND: The urea breath test (UBT) can still be improved in terms of user-friendliness and accuracy during acid-suppression therapy. This study was designed to evaluate a novel, rapidly disintegrating 13C UBT tablet, which was supplemented with citric acid to facilitate diagnosis of Helicobacter pylori in the hypochlorhydric stomach. METHODS: The efficacy of a fasting 13C tablet-based UBT (TUBT) was compared with that of a standard 13C UBT (SUBT) during 40 min after dosing, and optimal sampling points were determined. The single-point TUBT was validated against a 'gold standard' (GS) including a TUBT, culture, histology, and a CLO test in 134 dyspeptic patients, and its optimal cut-off point was determined by means of a biometric method. In addition, 20 SUBT-positive patients were randomized to perform either the TUBT or the SUBT after 7 days of omeprazole therapy (20 mg twice daily). RESULTS: Compared with a SUBT, the TUBT gave a quicker and wider separation between positive and negative results and an earlier optimal sampling point (10 versus 40 min). At 10 min the TUBT correctly classified 40 of 42 GS-positive subjects (sensitivity, 95%) and all of 92 GS-negative patients (specificity, 100%), and the optimal cut-off point was 1.8 delta per mil. Furthermore, when optimal sampling points were used, the TUBT (t = 10 min) proved to be more accurate than the SUBT (t = 40 min) during omeprazole treatment, correctly identifying all of 10 and 3 of 9 H. pylori-infected patients, respectively. CONCLUSIONS: By supplying 13C urea and citric acid as a rapid-release tablet, it is possible to shorten the duration of the 13C UBT to 10 min, omit the test meal, and still maintain excellent accuracy, even during acid suppression therapy.

Amide local anesthetics reduce albumin extravasation in burn injuries.

Burn injury was induced in anesthetized rats by exposing the abdominal skin to a temperature of 55 degrees C by means of a hot aluminum rod. Temperature was registered on a Grass polygraph. Skin exposure was interrupted when hot rod temperature had decreased to 45 degrees C. A full-thickness burn trauma of the skin was induced as judged from histologic sections. The burned skin was dissected and extravasation of Evans blue (EB) bound plasma albumin was quantified by a spectrophotometric technique and visualized by fluorescence microscopy. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA) for 1.5 h starting 15 min after inducing the burn injury. In one control group (n = 14) the thermal injury was treated with placebo cream. A second control group (n = 15) was topically treated with placebo cream without being exposed to thermal trauma. Results showed a significant inhibition of EB-albumin extravasation in the skin of burned rats treated with lidocaine-prilocaine cream compared with placebo-treated burned skin (P less than 0.001). EB-albumin contents in the skin of burned rats treated with lidocaine-prilocaine cream did not differ significantly from unburned skin (P greater than 0.05). In the second set of experiments continuous iv lidocaine infusions at a rate of 5 (n = 10), 10 (n = 12), 20 (n = 10), or 30 (n = 10) micrograms.kg-1.min-1 was given.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of the subepithelial resistance for the electrical properties of the rat jejunum in vitro.

The aim of the study was to evaluate full-thickness and partially stripped jejunum as a model for neurogenic control of electrogenic ion transport. The electrical properties of full-thickness and partially stripped segments were studied in Ussing chambers. Using square-pulse analysis, subepithelial and epithelial resistances (Rs and Rp) were determined, and by compensating for the potential fall across Rs, the current generated by the epithelium could be measured. In full-thickness tissue, Rs was approximately 80% of total tissue resistance, and the current measured during short-circuiting of the whole tissue (SCC) was therefore only 20-25% of the current generated by the epithelium (Im). Surgical stripping of the tissue decreased Rs by 10-20%. This means that in full thickness as well as in stripped tissue, 70-80% of the potential difference across the epithelial layer remains after traditional 'short circuiting'. Over a 25-min period, none of the electrical parameters changed significantly in the full-thickness tissues. In the stripped group PD, SCC and Im fell significantly, and in parallel during the same period of time. Neither glucose, noradrenaline, met-enkephalin or carbachol had any significant effect on Rs, Rp or the Rs/Rp ratio. The relative effects of these agents on Im and SCC were therefore similar. Substance P and VIP increased the Rs/Rp ratio significantly and, therefore, the effect of these drugs on Im was significantly more pronounced than the effect on SCC. The results show that the subepithelial resistance must be taken into account when the electrogenic activity in the epithelium is to be determined correctly. Conventionally measured SCC reflects the electrogenic effect of the tested putative neurotransmitters, but the magnitude of the responses is grossly underestimated, particularly for substance P and VIP.

Simultaneous measurements of gastric motility and acid-bicarbonate secretions in the anaesthetized cat.

Chloralosed cats were acutely vagotomized, their splanchnic nerves cut and the adrenal glands ligated. The gastric lumen was perfused with isotonic NaCl and gastric motility was monitored as changes in hydrostatic pressure within the perfusion circuit. Gastric secretion of H+ and HCO3- were calculated from continuous measurements of pH and PCO2. Methodological tests ex vivo showed good accuracy of the estimations. Recovery of H+ after HCl instillation into the stomach in vivo was almost complete, while HCO3- recovery after NaHCO3 instillations was 85-95%. Pentagastrin (10 micrograms kg-1 h-1 i.v.) stimulated gastric contractile activity and increased gastric H+ secretion 30-fold, while HCO3- secretion decreased somewhat. Carbachol (4 micrograms kg-1 h-1) induced gastric contractions and increased H+ secretion by 400% and HCO3- output by 100-130%. Electrical stimulation of the cut vagal nerves (10 Hz for 10 min) induced well known gastric motor responses and increased gastric H+ secretion 20-fold preceded by a transient doubling of HCO3- secretion. Omeprazole, a selective inhibitor of gastric H+ secretion, decreased the vagally induced H+ secretion, while recorded gastric HCO3- secretion was clearly enhanced. In conclusion, the technique permits simultaneous recordings of rapid alterations of gastric motility and H+ and HCO3- secretions. However, HCO3- secretion was modestly underestimated, probably due to mucosal CO2 absorption.

Cerebral function during hypotensive haemorrhage in spontaneously hypertensive rats and Wistar Kyoto rats.

Studies on cerebral function during cerebral ischaemia are usually performed on conscious animals after ligation of a major vessel supplying the brain. In this work, we studied somatosensory evoked potentials (SEP) in chloralose-anaesthetized Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) during hypotensive haemorrhage, with the main emphasis on the SHR which are more vulnerable. The main purpose was to see whether haemorrhaged SHR could be used for studies of cerebral function during relative cerebral ischaemia in anaesthetized rats. The mean arterial pressure (MAP) was rapidly lowered to 45-50 mm Hg and maintained at that level by adjustments of bleeding and transfusion. This resulted in pronounced sympathetic inhibition and bradycardia in all rats. In SHR, this sympatho-inhibitory response was usually reversed after about 20 min. In one group of hypertensive rats (SHRt, n = 24), MAP was raised to 75 mm Hg by partial re-transfusion, when heart rate (HR) had returned to the pre-bleeding level and MAP was maintained at that level for the rest of the experiment. All the other rats (SHR, n = 12; WKY, n = 11) were kept at 45-50 mm Hg for 32 min, after which WKY were bled further to a MAP of 30 mm Hg for 8 min. SEP amplitudes decreased after haemorrhage in all groups but more so in SHR. In the WKY group, SEP were only modestly attenuated during the first 32 min, but after further bleeding to 30 mm Hg the amplitudes were reduced to the same extent as in SHR. Some SHR showed flat SEP immediately upon haemorrhage and were excluded from the SHRt group.(ABSTRACT TRUNCATED AT 250 WORDS)

On-line computer evaluation of dye indicator dilution curves for determinations of capillary diffusion capacities.

A colourimetric indicator diffusion method has been modified to obtain more rapid and less elaborate estimations of the permeability surface area product (PS). The venous light absorbance curves of an intravascular reference substance and a permeable tracer substance are collected by a computer, which immediately presents the concentration curves versus time. Collected data are saved on diskettes. The data are normalized with respect to calibration and fractional as well as integrated capillary extraction values are presented. Extraction values can then be freely chosen for calculations of PS. The program is designed to give maximum precision and safety in the handling of calibrations and collected data. Albumin, labelled with cardiogreen, is used as reference dye and CrEDTA (MW = 341) or cyanocobalamine (vitamin B12, MW = 1355) as tracer. All dyes showed linearity between concentration and densitometer output in the concentration interval used. Both spatial and temporal accuracy of colourimetric recordings are superior to radioactivity measurements. However, the technique is so far limited to the use of cell-free perfusates.

Morphometric study of mesenteric and renal arteries in spontaneously hypertensive rats.

Arteries from spontaneously hypertensive rats (SHR), stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto controls (WKY) were fixed by immersion and plastic embedded. The media cross-sectional area and the length of the internal elastic membrane were measured. The ratio between media thickness and internal radius was then calculated for a standardized condition, implying a perfectly smooth and circular internal elastic membrane. An increase of the media to radius ratio was already demonstrable in visceral arterial branches of SHR and SHRSP by 15 days of age, indicating that changes of arterial structure could be of pathogenetic importance in early hypertension. At seven months of age the ratio was significantly increased in mesenteric arterial branches of SHR and SHRSP and in renal arterial branches of SHRSP. The media to radius ratio was markedly increased in the renal and superior mesenteric arterial trunks of adult SHR (P less than 0.001 in both) and SHRSP (P less than 0.001 and P less than 0.01). This was due to a greater media cross-sectional area in the former vessels and to a combination of greater media and reduced radius in the latter.

An "on-line" colorimetric method for repeated, rapid determinations of capillary diffusion capacity.

The single injection indicator diffusion method for estimation of capillary diffusion capacity (Crone 1963) has been developed to provide directly visualized, continuous colorimetric recordings of the venous time-concentration curves by means of a two-colour densitometer system. Cardio-Green, bound to albumin, is used as the non-permeant ("reference") tracer and Cr-EDTA as the permeant one. The artificially perfused hindquarter muscle vascular bed of rats is used. Highly reproducible curve recordings can be obtained every fourth minute. Accidental disturbances of the recordings are readily detected. Thus, compared to the fractional venous sampling technique, the present technique has the great advantage of allowing immediately controlled and frequently repeated determinations of capillary diffusion capacity. It is therefore easily used together with measurements of filtration-absorption events, e.g. for frequent quantitative comparisons of capillary diffusion and filtration capacities over a wide range of induced changes in perfused capillary surface area and/or capillary permeability. The main limitation is that the employed permeant tracer necessitates the use of erythrocyte-free perfusates.

Transmembrane fluxes of potassium in dog kidney slices. A quantitation of the effect of warm ischemia.

The effect of warm ischemia on the transmembrane transport of potassium in dog kidney slices was studied by measurement of the uptake of 42K. The requirement for steady-state conditions concerning the intracellular potassium concentration was thereby studied. The total potassium content in the slices was found to be constant between 120 and 180 min incubation at both 25 and 37 degrees C. The cell water calculated from the total tissue water and 14C-inulin space in the dog kidney slices amounted to 38 ml-100 g wet weight-1 at 37 degrees C and 45 ml-100 g wet weight-1 at 25 degrees C and was found to remain constant for the incubation interval 120--180 min. The major part of the tissue uptake of 42K could be described by one single mono-exponential function under these conditions. The transmembrane influx at 37 degrees C calculated by using a modified Keynes formula amounted to 1.70 mmol K+-kg wet weight-1-min-1 after no warm ischemia and to 0.89 mmol K+-kg wet weight-1-min-1 after 2 h warm ischemia. The corresponding values for incubation at 25 degrees C were 1.26 and 0.77 mmol K+-kg wet weight-1-min-1, respectively. In the slices incubated at 25 degrees C, the potassium content was higher and the sodium content lower than in slices incubated at 37 degrees C.

Arterial pressure, cardiac output and systemic resistance before and after pithing in normotensive and spontaneously hypertensive rats.

After complete cardiovascular denervation mean arterial pressure (MAP) falls to almost equally low levels in spontaneously hypertensive rats (SHR) and normotensive control rats (NCR). This has earlier been suggested to indicate a dominance of neurogenic mechanisms in established SHR hypertension. -- In the present study, total peripheral resistance (TPR) remains, however, some 35 per cent higher in adult SHR than in NCR after pithing while cardiac output (CO), and stroke volume, is 35 per cent lower in SHR. These opposite differences in TPR and CO after denervation, resulting in equal MAP levels in SHR and NCR, seem rather to be a consequence of the rapidly established structural adaptation that affects all SHR high-pressure cardiovascular sections. Thus, the SHR precapillary resistance vessels display thickened walls and luminal narrowing, which keeps TPR higher than in NCR even during maximal vasodilatation. Due to hypertrophy, the SHR left ventricle exhibits a reduced myocardial stretch for a given filling pressure and stroke volume is consequently reduced more than in NCR after complete denervation. -- Paradoxically, therefore, rather than reflecting any dominance of neurogenic mechanisms in established SHR hypertension the MAP equalization in SHR and NCR after cardiovascular denervation emphasizes the hemodynamic importance of cardiovascular structural changes present in hypertension.