Acute volaemic changes modify the gastroduodenal resistance to the flow of saline in anaesthetized dogs

The effect of acute and sequential volaemic changes on the gastroduodenal flow of saline was assessed in 23 anaesthetized dogs following two different experimental protocols. Hypervolaemia, by i. v. infusion of saline, induced a gradual decrease on gastroduodenal flow which amounted to 76% below control values (P < 0.001) when volaemic expansion attained 5% of body weight. This effect was volume dependent (17% increase on gastroduodenal flow per volume of infused saline equivalent to 0.5% of body weight, P < 0.001), lasted for at least 90 minutes after infusion was completed and was also obtained by expanding previously bled animals. Hypovolaemia due to bleeding was followed by an increase on gastroduodenal flow of about 88% above control values (P < 0.05) when haemorrhage was equal to 3% of body weight. This effect was also volume dependent (23 % increase on gastroduodenal flow per volume of blood shed equivalent to a 0.5% of body weight, P < 0.01) and was reversed after blood volume was restored. These modifications in the resistance of the gastroduodenal segment to the flow of liquid due to acute volaemic changes suggest that the extracellular fluid volume modulates the contractile activity of the gastroduodenal portion of the gut possibly to set a gastroduodenal handling of liquid adequate to cope with volaemic imbalances.     

Sexual behavior and 2-deoxyglucose uptake in male red-sided garter snakes (Thamnophis sirtalis parietalis).

The [14C]2-deoxyglucose (2-DG) technique was used to study patterns of neural activity associated with the species-typical courtship behavior of male red-sided garter snakes (Thamnophis sirtalis parietalis). Males in this species court females intensely during the first month following spring emergence from their prolonged winter hibernation. Autoradiographic methods were used to measure the accumulation of radioactive label in various regions through the brains of male garter snakes that courted females, males that failed to court females, and males not exposed to females. Male garter snakes that actively courted females showed a pronounced increase in 2-DG accumulation, and therefore presumably neural activity, in the region of the anterior hypothalamus/preoptic area, relative to males that did not actively court females. Males exposed to females (regardless of whether they courted or not) showed widespread, non-specific increases in 2-DG uptake relative to males not exposed to females. The results indicate the utility of the 2-DG technique for studying complex, species-typical behaviors in vertebrates.     

Brain metabolism and blood flow in acute cerebral hypoxia studied by NMR spectroscopy and hydrogen clearance.

We have developed a reliable, reproducible model of hypoxia in the gerbil. 1H and 31P NMR spectroscopy demonstrates that cerebral energy metabolism is very resistant to hypoxia. Cerebral blood flow (measured by hydrogen clearance) began to increase when the arterial oxygen tension (paO2) was reduced to 40-50 mm Hg, and there was no change in phosphorus metabolites or lactate until paO2 was below 40 mm Hg. In 50% of the animals lactate increased prior to any change in the phosphorus metabolites or intracellular pH, suggesting that 1H NMR may be more sensitive than 31P NMR at detecting hypoxic or ischaemic changes. The calculated rate of oxygen delivery at a time when phosphorus energy metabolism becomes impaired is similar in both hypoxia and ischaemia (ca 4mL/100 g/min). We suggest that the critical factor in ischaemia is the reduction in oxygen supply, rather than the accumulation of toxic metabolites, such as lactate.     

Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

BACKGROUND: Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. METHODS: In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. RESULTS: There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. CONCLUSIONS: These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.     

Wireless pH testing as an adjunct to unsedated transnasal esophagoscopy: the safety and efficacy of transnasal telemetry capsule placement.

OBJECTIVES: The introduction of 48-hour wireless pH testing offers clinicians a new alternative for the objective documentation of reflux. The success of transnasal wireless pH capsule placement has not been previously described. The purpose of this investigation was to describe our experience with transnasal wireless pH capsule placement. METHODOLOGY: All patients undergoing unsedated transnasal esophagoscopy and wireless pH capsule placement between January 1, 2003 and July 31, 2003 were prospectively evaluated. Data concerning patient tolerance, success of capsule placement and function, complications, and pH recordings were collected. RESULTS: During this time, 46 persons were evaluated. The mean age of the cohort was 52 years. Of the patients, 50% were male. The indications for the procedure were chronic cough (18/46), gastroesophageal reflux disease (18/46), and larygopharyngeal reflux (10). Of the procedures performed, 85% (39/46) were successful. Complications included epistaxis (2/46), laryngospasm (2/46), and vasovagal reaction (1/46). CONCLUSIONS: The transnasal placement of a wireless pH capsule is a safe and effective diagnostic adjunct to unsedated transnasal esophagoscopy.