Effect of ipriflavone on bone in elderly hemiplegic stroke patients with hypovitaminosis D.

A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side, correlating with the degree of paralysis and vitamin D deficiency due to malnutrition, sunlight deprivation, and immobilization-induced hypercalcemia, and increases the risk of hip fracture. We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [1alpha(OH)D3; vitamin D3] administration on bone mineral density preservation as compared with untreated controls. In a randomized and prospective study of 103 patients with hemiplegia after stroke (the mean duration of illness was 4.8 yr), 68 (34 patients in each group) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo, whereas the remaining 35 patients received no drug. Bone mineral density on the hemiplegic side decreased by 1.4% in the ipriflavone group, 3.8% in the vitamin D3 group, and 5.4% in the control group (P < .0001, ipriflavone v vitamin D3 and control). At baseline, all three groups of patients showed a 25-hydroxyvitamin D insufficiency, increased serum ionized calcium, and low levels of 1, 25-dihydroxyvitamin D, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1, 25-dihydroxyvitamin D. After treatment, the serum 1, 25-dihydroxyvitamin D level increased by 139.9% in the ipriflavone group and by 26.9% in the vitamin D3 group. Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group, whereas no changes occurred in the other two groups. One patient in the untreated group suffered a hip fracture, compared with none in the ipriflavone and vitamin D3 groups. These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1, 25-dihydroxyvitamin D concentration.     

Left atrial volume: predictor of atrial fibrillation in patients with degenerative mitral regurgitation

BACKGROUND AND AIM OF THE STUDY: In patients with mitral regurgitation (MR) due to degenerative mitral valve prolapse (MVP), preoperative atrial fibrillation (AF) has been identified as an independent predictor of survival after surgery for MR. Thus, the determinants of preoperative AF may have critical implications to evaluate the timing of mitral valve repair. The study aim was to investigate the role of left atrial (LA) volume in predicting preoperative AF in patients with severe MR due to degenerative MVP. METHODS: Sixty-six patients with severe degenerative MR (regurgitant volume > or =60 ml, regurgitant fraction > or =50%, effective regurgitant orifice area > or =0.4 cm(2)) in sinus rhythm (SR) at diagnosis and conservatively managed were eligible for the study. Complete two-dimensional (2-D) echocardiographic and Doppler measurements, including the measurement of maximum LA volume, were performed in all patients. RESULTS: During follow up under conservative management (18.1+/-4.8 months), eight patients (12%) experienced conversion to AF, and 58 remained in SR. The mean LA dimension was 4.0+/-0.5 cm in patients with SR, and 5.1+/-0.8 cm in those who developed AF (p <0.0001). The mean LA volume and LA volume index (indexed to body surface area) were 95 +/-23 ml and 60+/-14 ml/m(2) respectively in patients with SR, and 166+/-66 ml and 104+/-42 ml/m(2) respectively in those who developed AF (both p <0.0001). The optimal cut-off value for LA volume to predict AF conversion was 117.5 ml (sensitivity 88%, specificity 83%), and for LA volume index was 75 ml/m(2) (sensitivity 88%, specificity 88%). CONCLUSION: LA volume measurement should be considered in patients with degenerative severe MR diagnosed in SR. A LA volume index > or =75 ml/m(2) reflects the risk of subsequent AF, and patients should be closely monitored.     

Prognostic significance of macroscopic serosal invasion in advanced gastric cancer

BACKGROUND/AIMS: Although histologic invasion of the gastric serosa is associated with poor prognosis in patients with gastric cancer, the prognostic significance of macroscopic invasion of the serosa is not clear. The aim of this study was to clarify the clinical significance of macroscopic serosal invasion in advanced gastric cancer. METHODOLOGY: Clinicopathologic data from 257 patients who underwent curative gastrectomy for advanced gastric cancer was analyzed to evaluate the prognostic significance of macroscopic serosal invasion. On the basis of macroscopic findings, tumors were classified as SO, negative serosal invasion; S1, positive serosal invasion; or S2, invasion extending to the adjacent organ. We also examined the relation between the extent of macroscopic serosal invasion (SO, S1, S2) and volumetric shape of cancerous invasion (funnel, column, and mountain types). RESULTS: In comparison with SO tumors, S1 and S2 tumors were significantly more likely to be more than 5cm in diameter and show histologically serosal invasion. Volumetric analysis showed that S1 and S2 tumors were more frequently column- or mountain-shaped than were SO tumors. The 5-year survival rate differed significantly between patients with SO, S1, and S2 tumors (88% us. 65% vs. 18%, P<0.01). Multivariate analysis indicated that macroscopic serosal invasion was an independent prognostic factor. CONCLUSIONS: Macroscopic serosal invasion is associated with extensive cancerous invasion of the deep gastric wall. The presence of macroscopic serosal invasion indicates advanced tumor progression and poor prognosis for patients with advanced gastric cancer. Clinically, knowledge of the extent of macroscopic serosal invasion is helpful in planning adjuvant chemotherapy.     

2-Decenoic acid ethyl ester possesses neurotrophin-like activities to facilitate intracellular signals and increase synapse-specific proteins in neurons cultured from embryonic rat brain

We presently found that medium-chain fatty acids (MCFAs) with 8-12 carbons and their esters facilitated activation (phosphorylation) of mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK) 1/2 of cultured embryonic cortical/hippocampal neurons. In particular, trans-2-decenoic acid ethyl ester (DAEE) had the most potent activity. Additionally, DAEE activated phosphatidylinositol 3-kinase and cAMP-response element binding protein (CREB), suggesting that DAEE generates similar intracellular signal as neurotrophins. Therefore, details of the signal elicited by DAEE were examined in comparison with those of a neurotrophin, brain-derived neurotrophic factor (BDNF). We found that 1) DAEE phosphorylated MAPK/ERK1/2 via MEK activation without the involvement of tyrosine kinases of neurotrophin Trk receptors; 2) DAEE activated CREB predominantly through MAPK/ERK1/2 activation, not through other pathways such as cAMP/protein kinase A; and 3) DAEE increased the expression of RNAs of BDNF and neurotrophin-3 and the protein content of synapse-specific proteins such as synaptophysin, synapsin-1, and syntaxin. Based on these observations we propose that DAEE and some other derivatives of MCFAs having neurotrophin-like neurotrophic activities may become therapeutic tools for certain neurological or psychiatric disorders.     

Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy

Globoid cell leukodystrophy (GLD; also known as Krabbe disease) is an invariably fatal lysosomal storage disorder caused by mutations in the galactocerebrosidase (GALC) gene. Hematopoietic stem cell (HSC)-based gene therapy is being explored for GLD; however, we found that forced GALC expression was toxic to HSCs and early progenitors, highlighting the need for improved regulation of vector expression. We used a genetic reporter strategy based on lentiviral vectors to detect microRNA activity in hematopoietic cells at single-cell resolution. We report that miR-126 and miR-130a were expressed in HSCs and early progenitors from both mice and humans, but not in differentiated progeny. Moreover, repopulating HSCs could be purified solely on the basis of miRNA expression, providing a new method relevant for human HSC isolation. By incorporating miR-126 target sequences into a GALC-expressing vector, we suppressed GALC expression in HSCs while maintaining robust expression in mature hematopoietic cells. This approach protected HSCs from GALC toxicity and allowed successful treatment of a mouse GLD model, providing a rationale to explore HSC-based gene therapy for GLD.     

Solitary intrapulmonary cystic lymphangioma in an infant: a case report with literature review

Lymphangioma rarely presents as a solitary pulmonary lesion. We encountered a case of solitary cystic lymphangioma and present its clinicopathologic and immunohistochemical findings. A 2-month-old boy was referred to the hospital after developing a persistent cough. Chest X-ray showed a large cyst in the right lung. Under the preoperative diagnosis of bronchogenic cyst, he underwent right lower lobectomy at the age of 11 months. The resected specimen contained a 5.5-cm septate cystic lesion. Microscopically, the lesion consisted of a large cystic space and interconnected slit-like spaces surrounding bronchovascular islands. The cyst was lined by a monolayer of flat cells with focal multinucleated giant cells. Immunohistochemically, the cells lining the cystic lesion were positive for D2-40, Prox1, CD34, and CD31, and weakly positive for VEGFR-3, but were negative for AE1/3, HMB45, VEGF-A, VFGF-C, VEGFR-1. Differential diagnoses included lobar or interstitial emphysema, bronchogenic cyst, congenital pulmonary airway malformation and alveolar adenoma. D2-40 and Prox1 were useful in differentiation and in determining the extent of the lesion. A review of the literature found only 15 cases of solitary pulmonary lymphangioma. In younger patients, the lesions tend to occupy more of the lung. Focal giant cell reaction has not been described in the reported papers.     

Ramp rate of blood pressure changes does not affect aortic afferent sensitivity in anesthetized rats

To investigate whether the rate of change in blood pressure affects the sensitivity of the aortic baroreceptor afferent response, the change in aortic nerve activity (ANA) to two different rates of ramp increase in mean blood pressure (MBP), elicited by phenylephrine administration, was determined in the rat under urethane (1.5 g kg⁻¹) anesthesia. The sensitivity of the increase in ANA following a rapid (average ramp rate, 9.14 ± 0.60 mmHg s⁻¹, n = 11) or gradual (1.78 ± 0.24 mmHg s⁻¹, n = 11) increase in MBP was 2.03 ± 0.14% and 1.81 ± 0.20% of baseline mmHg⁻¹, respectively. These values were not significantly different from each other (P = 0.16). Furthermore, we found no correlation between the rate of ramp increase in MBP and the sensitivity of the increase in ANA (r = 0.24, P = 0.29, n = 22). These results suggest that, at least within the normal physiological range of MBP, the rate of the ramp change in blood pressure does not affect aortic baroreceptor afferent sensitivity in the anesthetized rat.     

Successful management of pregnancy and delivery in a woman with multiple coronary stenoses of unknown cause

We describe the case of a 30-year-old primiparous woman who had multiple coronary stenoses of unknown cause, and discuss causes and risks in pregnancy in a patient with coronary stenoses and the management and outcome. At 13 years of age, the patient was diagnosed as having multiple coronary stenoses and percutaneous transluminal coronary angioplasty was performed. At the age of 30, coronary arteriography demonstrated multiple severe stenoses. Her previous physician had permitted her to become pregnant. At 32 weeks' gestation, due to uncontrollable uterine contractions, magnesium sulfate was administered. At 37 weeks' gestation, a cesarean section was performed because of breech presentation, and she delivered a healthy female infant. During cesarean section, oxytocin was given at a slower rate. There has been no recurrence of cardiac events during and after pregnancy. Multiple coronary stenoses during pregnancy need a multidisciplinary approach.