Highly efficient ex vivo gene transfer to the transplanted heart by means of hypothermic perfusion with a low dose of adenoviral vector

BACKGROUND: Hypothermic conditions required for donor heart preservation may reduce gene-transfer efficiency. Experiments were designed to determine whether a perfusion technique could improve the efficiency of gene transfer to donor hearts. METHODS: An adenoviral vector encoding beta-galactosidase (3.5 x 10(8) plaque-forming units) was infused into explanted rat hearts under 4 conditions (each n = 6): (1) the virus was diluted in 350 microL of University of Wisconsin solution and infused as a high-pressure bolus into the coronary arteries of donor hearts through the aortic root; (2) the virus was diluted in 5 mL of University of Wisconsin solution and circulated by means of a peristaltic pump (flow, 0.75 mL/min) through the vasculature of the donor heart for 30 minutes; (3) 5 mL of viral solution was circulated as for group 2 for 15 minutes; and (4) 5 mL of viral solution was circulated for 5 minutes at a flow rate of 2.4 mL/min. Transduced hearts were transplanted into the abdomen of syngeneic rats, and transgene expression was assessed by means of immunoassay 4 days later. RESULTS: The median beta-galactosidase content was (1) 45.0 ng/mg protein (25th-75th percentile, 33-73 ng/mg), (2) 640 ng/mg protein (25th-75th percentile, 614-878 ng/mg), (3) 493.8 ng/mg protein (25th-75th percentile, 456-527 ng/mg), and (4) 503.3 ng/mg protein (25th-75th percentile, 475-562 ng/mg; P <.01 for group 2 vs group 1, and P <.05 for groups 3 and 4 vs group 1). Transgene expression was predominantly in myocytes and favored the subepicardial region of the right ventricle. CONCLUSION: Hypothermic perfusion of the donor heart with an adenoviral vector resulted in efficient transgene expression compared with that induced by a single bolus injection.     

Usefulness of measuring the gastric emptying time in a case of brittle diabetes

Gastric emptying time measurement by radionuclide study, although quite informative, is rarely remembered in clinical practice. We presented a patient with brittle diabetes who had multiple emergency admissions due to hypoglycemia under routinely prescribed insulin therapy. She had severe gastroparesis, which was determined by scintigraphic gastric emptying study (gastric half-emptying time = 260 min for a mixed meal). She had not presented to the emergency service for two years because of only a slight change the timing of her insulin administration time (after meal instead of before meal) in the light of gastric-emptying study.     

The added value of the apparent diffusion coefficient calculation to magnetic resonance imaging in the differentiation and grading of malignant brain tumors

OBJECTIVE: ADC calculation can improve the diagnostic efficacy of MR imaging in brain tumor grading and differentiation. METHODS: Apparent diffusion coefficient (ADC) values and ratios of 33 low-grade (23 astrocytomas, 10 oligodendrogliomas) and 40 high-grade (25 metastases and 15 high-grade astrocytomas) malignant tumors were prospectively evaluated. RESULTS: Tumoral ADC values (r=-0.738, P <0.000) and ratios (r=-0.746, P < 0.000) were well correlated with higher degree of malignancy and quite effective in grading of malignant brain tumors (P < 0.000). By using cutoff values of 0.99 for tumoral ADC value and 1.22 for normalized ADC ratio, the sensitivity of MR imaging could be increased from 72.22% to 93.75% and 90.63%, the specificity from 81.08% to 92.68% and 90.24%, PPV from 78.79% to 90.91% and 87.88%, and NPV from 75.00% to 95.00% and 92.50%, respectively. CONCLUSION: ADC calculation was quite effective in grading of malignant brain tumors but not in differentiation of them and added more information to conventional contrast-enhanced MR imaging.     

How does subchorionic hematoma in the first trimester affect pregnancy outcomes?

IntroductionSubchorionic hematoma (SCH) in pregnancy has been associated with increased risk of adverse pregnancy outcomes. We aimed to investigate the association of SCH with adverse pregnancy outcomes in pregnant women in relation to size of hematoma and control subjects.Material and methodsThis study included 178 pregnant women with sono-graphically detected SCH in the 1^st trimester, and 350 pregnant controls without SCH. Data on maternal age, smoking status, gestational week at diagnosis, location of SCH, medications before diagnosis, gestational week at delivery, delivery route and pregnancy outcomes (first trimester vaginal bleeding, pre-eclampsia, gestational diabetes, intrauterine growth restriction (IUGR), placental abruption, preterm delivery < 37 weeks, early pregnancy loss and intrauterine death) were retrieved retrospectively from hospital records. Pregnant women with SCH were divided into 3 groups according to the size of hematoma including small SCH (SCH-I group, n = 47), medium-size SCH (SCH-II group, n = 110) and large SCH (SCH-III group, n = 21) groups.ResultsSubchorionic hematoma was associated with significantly lower gestational age at delivery (p < 0.001) and higher rate of first trimester bleeding (p < 0.001) compared with the control group, regardless of the size of the hematoma. Placental abruption (p = 0.002) and early pregnancy loss (p < 0.001) were significantly more common in SCH-II and -III groups than in the control group. SCH-III group was associated with a significantly higher rate of < 37 gestational weeks at delivery (p < 0.001), first trimester vaginal bleeding (p < 0.001), early pregnancy loss (p < 0.001), IUGR (p = 0.003) and preterm delivery (p < 0.001) compared to both lesser size hematoma and control groups.ConclusionsOur findings suggest that large SCH might indicate an increased risk of adverse pregnancy outcomes such as 1^st trimester vaginal bleeding, early pregnancy loss, IUGR, placental abruption or preterm delivery. These findings are important to guide the patients with SCH for detailed clinical evaluation.     

Laryngopharyngeal reflux and Helicobacter pylori

Laryngopharyngeal reflux (LPR) occurs when gastric contents pass the upper esophageal sphincter, causing symptoms such as hoarseness, sore throat, coughing, excess throat mucus, and globus. The pattern of reflux is different in LPR and gastroesophageal reflux. LPR usually occurs during the daytime in the upright position whereas gastroesophageal reflux disease more often occurs in the supine position at night-time or during sleep. Ambulatory 24-h double pH-probe monitoring is the gold standard diagnostic tool for LPR. Acid suppression with proton pump inhibitor on a long-term basis is the mainstay of treatment. Helicobacter pylori (H. pylori) is found in many sites including laryngeal mucosa and interarytenoid region. In this paper, we aim to present the relationship between LPR and H. pylori and review the current literature.