Ranitidine controls nocturnal gastric acid breakthrough on omeprazole: a controlled study in normal subjects

BACKGROUND & AIMS: Proton pump inhibitors administered twice daily do not provide complete nocturnal acid suppression. Acid breakthrough, or decrease in intragastric pH to <4 for an hour or longer, occurs in three quarters of normal subjects and patients at night. We compared the effect of a third dose of omeprazole at bedtime with that of a dose of ranitidine at bedtime on residual nocturnal acid secretion in patients receiving omeprazole twice daily. METHODS: Twelve volunteers underwent overnight intragastric pH monitoring after 7 days of treatment with omeprazole, 20 mg twice daily, followed by different treatment supplements at bedtime: placebo; additional omeprazole, 20 mg; ranitidine, 150 mg; and ranitidine, 300 mg. RESULTS: Additional omeprazole at bedtime reduced the percentage of time with intragastric pH of <4 from 48% to 31% (P < 0.005) compared with omeprazole twice daily with placebo at bedtime. Ranitidine at bedtime reduced this parameter more, 5% with 150 mg and 6% with 300 mg (P <0.01 vs. omeprazole twice daily plus bedtime). Results for percentage of time with intragastric pH <3 were similar. Eleven subjects had acid breakthrough with placebo at bedtime; 7 with omeprazole at bedtime (P = NS); 4 with ranitidine, 150 mg at bedtime; and 3 with ranitidine, 300 mg at bedtime (P < 0. 05, ranitidine vs. placebo). CONCLUSIONS: Bedtime ranitidine is more effective than bedtime omeprazole on residual nocturnal acid secretion in patients receiving omeprazole twice daily. This finding suggests that fasting breakthrough nocturnal acid secretion in patients receiving omeprazole twice daily is most likely histamine related.     

Proton nuclear magnetic resonance studies on dideoxyribonucleoside methylphosphonates

A series of dideoxyribonucleoside methylphosphonates, d-ApA, d-ApT, d-TpA, and TpT, were synthesized chemically and the diastereoisomers of each dimer were separated [Miller, P. S., Yano, J., Yano, E., Carroll, C., Jayaraman, K., & Ts'o, P. O. P. (1979) Biochemistry 18, 5134]. The 1H NMR spectra of these compounds are similar to those of their parent diester compounds. Specifically, the assignments of the 1H resonances of the two diastereoisomers of d-ApA (designated as 1 and 2) were reaffirmed by comparing with the unmodified, parent d-ApA. The absolute configuration of the phosphonate methyl group of the two isomers (d-ApA)1 and (d-ApA)2 was determined by the NOE technique. The 1H NMR spectra of the diastereoisomers of d-ApA, as well as the corresponding monomer components dAp and CH3pdA, and TpT were analyzed by spectrum simulation techniques. Thus, all the coupling constants and chemical shifts of the proton resonances of the deoxyribofuranose ring and the phosphonate methyl group could be precisely determined. These data provide the information for an analysis of the sugar puckering and backbone conformations of these novel nonionic nucleic acid analogues. It was found that the conformations of the sugar-phosphate backbones of each isomer are similar to each other and are similar to the conformations of the parent dinucleoside monophosphates. The average adenine stacking conformations of (d-ApA)1 and (d-ApA)2 were described in numerical coordinates derived from a computer analysis which included both ring-current magnetic anisotropy and atomic diamagnetic anisotropy effects. The two computer-derived conformational models are similar to those derived from the graphic approximation based only on the ring-current effects. For each pair of dimer analogues, the base stacking mode of isomer 1 is similar to that of its parent diester while the extent of base overlap in isomer 2 is less than that in isomer 1. The results of the conformational analysis based on NMR data are consistent with the results obtained from ultraviolet and circular dichroism measurements on these dimers.     

Adenoviral-mediated interferon-gamma gene therapy augments pulmonary host defense of ethanol-treated rats

A case of anuric acute renal failure due to bilateral renal artery obstruction in a 42 year-old man is presented. The obstruction was caused by bilateral thrombosis secondary to arteritis. Autopsy showed granulomatous and necrotizing vasculitis in both main renal arteries. Scarring and also necrotizing vasculitis were found from interlobular to arcuate renal arteries. The present case indicates that vasculitis should be considered when there is renal artery obstruction in young patients.     

Amino acid incorporation into liver and tumor proteins in patients with hepatic neoplasms-effects of liver dearterialization

The effects of liver dearterialization on the rate of amino acid incorporation into liver and tumor proteins were studied with an in vitro method in seven patients with liver metastases. Before liver dearterialization the incorporation rate was 0.074 +/- 0.020 nmol leucine x mg prot-1 x h-1 in liver tissue and 0.234 +/- 0.049 nmol leucine x mg prot-1 x h-1 in tumor tissue. After dearterialization for 1 h the incorporation rate was reduced to about half of the initial values in both liver and tumor tissue. The vascularity of the tumors was evaluated from preoperative hepatic angiograms. The reduction of the incorporation rate was more pronounced in highly vascularized tumors than in poorly vascularized tumors and liver tissue. The clinical implications of a more pronounced metabolic effect of the dearterialization in high vascularized tumors are discussed.     

Skeletal uptake of 99mTc-diphosphonate in relation to local bone blood flow

The right/left ratios of tibial uptake of 99mTc-diphosphonate (EHDP) and relative blood flow (based on microsphere distribution) were determined in control rats and rats with a ligated right femoral artery or a healing right tibial fracture. Correlation between 99mTc-EHDP uptake and relative blood flow was highly significant (r=0.917; P less than 0.0001) for relative flow ratios less than 1.7. When the ratio was greater than 1.7, there was little further increase in 99mTc-EHDP uptake. Ligation of the femoral artery in rats with healing fractures resulted in a more marked reduction of blood flow than of 99mTc-EHDP uptake. These results suggest that regional bone blood flow is a major determinant of 99mTc-EHDP uptake, though changes in regional tracer extraction efficiency are also important.