Extremely early onset of ranitidine action on human histamine H2 receptors expressed in HEK293 cells

BACKGROUND/AIMS: Histamine H2 receptor antagonists are considered to exert their effects on gastric acid secretion more rapidly than proton pump antagonists. However, there are no reports concerning the direct interaction of a histamine H2 receptor antagonist with the human H2 receptor in terms of onset of action. This study aims to characterize how rapidly famotidine and ranitidine, the most widely used histamine H2 receptor antagonists, interact with the human histamine H2 receptor. METHODS: HEK293 cell lines, stably expressing human histamine H2 receptors, were obtained. The dose- and time-dependent effects of famotidine and ranitidine on [3H]-tiotidine binding and histamine-stimulated cAMP production were analyzed. RESULTS: Ranitidine inhibited both [3H]-tiotidine binding and histamine-stimulated cAMP production more promptly than did famotidine. Inhibition of histamine-stimulated cAMP production by Cmax doses of famotidine (20 mg p.o.) and ranitidine (150 mg p.o.) peaked by 15 and 2 min, respectively. [3H]-tiotidine binding was not saturated by 60 min at the famotidine Cmax, while the ranitidine Cmax had produced saturation by 15 min. CONCLUSION: Ranitidine inhibits the human histamine H2 receptor very rapidly.     

Correlation between myocardial uptake of technetium-99m-sestamibi and pressure-derived myocardial fractional flow reserve

OBJECTIVES: Development of the coronary pressure wire has facilitated the measurement of fractional flow reserve (FFR) to assess the functional severity of coronary artery stenoses. METHODS: This study evaluated the correlations between FFR and myocardial direct counts of technetium-99m(99mTc)-sestamibi in 20 patients (16 men, 4 women, mean age 66 +/- 8 years) who underwent 99mTc-sestamibi single-photon emission computed tomography (SPECT) with the 2-day protocol using 740 MBq of 99mTc-sestamibi each day. Visual assessment of myocardial imaging and quantitative analysis with the measurement of percent uptake and direct count of 99mTc-sestamibi were performed. RESULTS: Visual assessment of myocardial imaging revealed that reversibility of 99mTc-sestamibi perfusion defects was correlated with FFR of < 0.75, which is regarded as functionally important stenosis (17/20 vs 3/20, kappa = 0.71, p < 0.002). Regional reversibility score did not correlate with FFR (r = -0.40, p = NS). Quantitative analysis revealed that the change in 99mTc-sestamibi percent uptake with pharmacologic stress using adenosine triphosphate disodium (ATP) also did not correlate with FFR (r = 0.35, p = NS). In contrast, percent increase in 99mTc direct counts with ATP was lower in patients with FFR of < 0.75 than in those with FFR of > = 0.75 (-4 +/- 16% vs 24 +/- 30%, p < 0.01). In addition, a significant correlation (r = 0.70, p < 0.001) was observed between percent increase in 99mTc direct counts with ATP and FFR. CONCLUSIONS: These results suggest that quantitative analysis of 99mTc-sestamibi scintigraphy enables the assessment of the magnitude of functional significance of coronary stenosis.     

Cholangiocarcinoma arising from preexisting biliary hamartoma of liver--report of a case

We describe the case of a 72-year-old asymptomatic man with a cholangiocarcinoma arising from a biliary hamartoma, also referred to as "von Meyenburg's complex". The patient was clinically diagnosed as having a cystadenocarcinoma, but the tumor had already been present as a uniformly low-density area on computed tomography taken four years previously, as revealed by retrospective examination of the computed tomography films that had been taken annually after surgery for pulmonary emphysema. The low-density area had continued to enlarge year after year, and a high-density area was observed to have emerged inside the low-density area on computed tomography. Histopathological examination demonstrated that the high-density area corresponded to the cholangiocarcinoma and the low-density area to a biliary hamartoma. This is the first case in which it was possible to confirm the presence of cholangiocarcinoma inside a biliary hamartoma that had continued to increase in size.     

Positron emission tomography-positive squalene-induced lipoid pneumonia confirmed by gas chromatography-mass spectrometry of bronchoalveolar lavage fluid

Squalene is a type of oil obtained from shark liver. We describe a 76-year-old man diagnosed with chronic exogenous lipoid pneumonia due to squalene. A chest CT scan revealed pulmonary consolidation with ground-glass opacities in the right upper lobe. Positron emission tomography (PET) revealed significant uptake of 2-deoxy-2-F-fluoro-d-glucose (FDG) and 3'-deoxy-3'-F-fluorothymidine (FLT). Bronchoalveolar lavage (BAL) fluid contained many lipid-laden macrophages, and a transbronchial lung biopsy specimen showed clusters of foamy macrophages in alveolar spaces and granulomatous lesions. In addition, the presence of squalene in the BAL fluid was confirmed by gas chromatography-mass spectrometry, leading to a diagnosis of squalene-induced lipoid pneumonia. To the best of our knowledge, this is the first report of squalene-induced lipoid pneumonia in which squalene itself was successfully detected. This case also suggests the possibility that lipoid pneumonia shows significant uptake in FDG-PET and FLT-PET.     

A case of intractable hemoptysis originating from the branches of the right subclavian artery, successfully treated with arterial coil embolization]

A 30-year-old woman was admitted because of persistent and severe hemoptysis in November 2005. She had been given a diagnosis of interstitial pneumonia (IP) and pulmonary aspergilloma in 2001, and she was treated with oral prednisolone and itraconazole. However she had persistent and intractable hemoptysis. Multi-detector row computed tomography (MDCT) revealed that hemoptysis from the right upper lobe did not originate in bronchial arteries, but the abnormal branches of the right subclavian artery. Surgery was not performed because of her pulmonary function, but she was successfully treated by non-bronchial arterial coil embolization. At 10 months after the embolization, hemoptysis has not recurred. MDCT was very useful for diagnosing the cause of hemoptysis and selective nonbronchial arterial coil embolization might be helpful in treating intractable or refractory hemoptysis.     

A new mutation in exon 12 of the gp91-phox gene leading to cytochrome b- positive X-linked chronic granulomatous disease

We have previously reported a patient with cytochrome b-positive X- linked chronic granulomatous disease. Although the O2- production of neutrophils from the patient was completely defective, we presented data suggesting that the patient's cytochrome b was present at a normal level and possibly had normal spectroscopic features. Thus, to look for a mutation in the cytochrome b heavy chain (gp91-phox) gene, DNA analysis of gp91-phox cDNA derived from this patient was performed. As a result, we found that five nucleotides (1521 through 1525) within exon 12 were deleted, and a new sequence of eight nucleotides was inserted. This mutation converted Gln507-Lys508-Thr509 into His-Ile-Trp- Ala. Mismatched polymerase chain reaction showed that the mother has both wild and mutated alleles, confirming that this case was transmitted in an X-linked fashion. This mutation is different from those previously reported by others. The translocation of p47-phox and p67-phox to the membrane fraction occurred, indicating the complete formation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. We conclude that this case suggests that the structure encoded on exon 12 of gp91-phox is important for electron transfer.     

Intracontinental and intercontinental dissemination of Asian H5 highly pathogenic avian influenza virus (clade 2.3.4.4) in the winter of 2014–2015

Asian H5 highly pathogenic avian influenza viruses (HPAIVs) that possess the clade 2.3.4.4 HA gene have been identified in wild birds and poultry since late 2014 in both Europe and North America (N. America). Clade 2.3.4.4 H5 HPAIVs of the H5N8 subtype have been isolated in both regions, whereas reassortment viruses with NA N1 and N2 subtypes of the North American (N. American). avian lineage have only been identified in N. America. The HA genes of those isolates were closely related to genes of the HPAIVs that have caused massive outbreaks in poultry in Korea since January 2014. The outbreaks caused by those viruses and the genetic relatedness of their HA and NA genes are reviewed in this study. Although the illegal movement of poultry and poultry products cannot be ruled out as a cause of intercontinental and intracontinental dissemination of clade 2.3.4.4 H5 HPAIVs during the winter of 2014–2015, transmission of the viruses by infected migratory birds appears to be a more plausible mechanism for their dissemination. In particular, the involvement of migratory birds in HPAIV transmission between Asia and N. America is highly likely because of the reassortments between H5N8 HPAIV and the N. American lineage avian influenza viruses. Copyright © 2015 John Wiley & Sons, Ltd.