Fetal facial expressions in small-for-gestational-age and growth-restricted fetuses

Objective: To evaluate the frequencies of fetal facial expressions among appropriate-for-gestational-age (AGA), small-for-gestational-age (SGA), and growth-restricted (FGR) fetuses.

Methods: Four-dimensional (4D) ultrasound was used to examine the facial expressions of 50 AGA, 25 SGA, and six FGR fetuses between 28 and 35 weeks of gestation. The frequencies of seven facial expressions during 15-minute recordings were assessed. Comparison of facial expressions among the three groups was performed.

Results: Mouthing was the commonest facial expression at 28–35 weeks, and the frequency of mouthing was significantly higher than those of the other six facial expressions in AGA fetuses. Mouthing was the most frequent facial expression, but there was no significant difference in the frequency among mouthing, smiling and blinking in SGA fetuses. Moreover, mouthing displayed a significantly higher frequency than the other facial expressions, except for yawning, smiling, and blinking in FGR fetuses. However, there was no significant difference in the frequency of each facial expression among the three groups.

Conclusions: Our results suggest that the frequencies of fetal facial expressions are not decreased in either SGA or FGR pregnancies. The absence of a decrease in the frequency of each fetal expression in FGR fetuses may be due to increased brain blood flow because of the brain-sparing effect. Moreover, accelerated maturation and development of the brain function, especially the central dopamine system, might be suspected in SGA and FGR fetuses.     

Enhanced Percolation and Gene Expression in Tumor Hypoxia by PEGylated Polyplex Micelles

In regard to gene vectors for cancer gene therapy, their percolation into the tumor tissue should be essential for successful outcome. Here, we studied the tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous tumors. As a result, polyethylene glycolated (PEGylated), core–shell type polyplexes (polyplex micelles) showed facilitated percolation and improved transfection inside the tumor tissue, whereas conventional polyplexes from cationic polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of hypoxia-responsive plasmid demonstrated that polyplex micelles allowed the transfection to the hypoxic region of the tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue.     

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.     

Can negative cardiac effect of proton pump inhibitor and high-dose H2-blocker have clinical influence on patients with stable angina?

BACKGROUND: Aspirin and anti-platelet drugs are used commonly for patients with coronary heart disease. Proton pump inhibitor (PPI) and high-dose H2-blocker were recommended for preventing NSAIDs-related ulcer. Previously H2-blocker reported to have some negative cardiovascular effects. Additionally, a recent in vitro study showed that PPI reduced cardiac contractility. In this study, we evaluated whether chronic administration of PPI and high-dose H2-blocker affects left ventricular function. METHOD: Fifty-two stable angina patients were enrolled and classified into PPI group ([P]; lansoprazole: 15mg/day, n=28), H2-blocker group ([H]; famotidine: 40mg/day, n=8), and control ([C]; none or mucosal-defense drug, n=16). Eligible patients showed normal cardiac function in initial catheterization without administrated PPI or H2-blocker. They received percutaneous coronary intervention and follow-up catheterization. We compared changes in ejection fraction (EF: %), end diastolic/systolic volume index (EDVI/ESVI: ml/m(2)), and peak positive/negative dp/dt (+/-dp/dt: mmHg/s) in left ventricular angiography series. RESULT: There were no significant differences among three groups regarding patient characteristics, backgrounds of angiographic and intervention, except for fewer smokers in [C]. Other drugs such as beta- and Ca-blocker did not have effects on cardiac function except for aspirin during 255+/-115 days follow-up. Rate of EF changes significantly decreased in [P], and tended to decrease in [H] (C: 3.8+/-9.8%, H: -1.6+/-7.6%, P: -2.1+/-5.9%; p<0.05 for [C] vs. [P]). Those of ESVI changes were significantly greater in [P], and tended to be greater in [H] (C: -4.5+/-16.2%, H: 4.9+/-15.5%, P: 7.3+/-16.2%; p<0.05 for [C] vs. [P]), though, EDVI changes' were similar (C: 2.5+/-8.9%, H: 2.6+/-3.6%, P: 1.6+/-6.1%; p=ns). Rate of +/-dp/dt-changes tended to decrease in [H] (+dp/dt: C: 3.9+/-15.5%, H: -10.0+/-25.2%, P: 0.3+/-19.6%; p=ns, -dp/dt: C: -0.1+/-19.5%, H: -8.5+/-20.4%, P: 5.7+/-27.7%; p=ns). CONCLUSION: In this study, PPI and high-dose H2-blocker have EF-reducing tendency. However, these changes were small and these drugs seemed to exhibit little influence clinically.     

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.