Mitral valve replacement in children under 3 years of age

Objective: This study was undertaken to review our experience of mitral valve replacement in children under 3 years of age. Methods: Between January 1990 and May 2004,18 patients under 3 years of age underwent a total of 20 mitral valve replacements using a bileaflet mechanical prosthetic valve. There were 9 males and 11 females. The age at surgery ranged from 3 months to 3 (mean=1.02±0.72) years and body weight varied between 3.4 and 13.2 (mean=7.08±2.74) kg. Results: There were 4 early and 2 late deaths, and these occurred in severe cases aged less than 1 year of age. Re-replacement of mitral valve was required in 3 patients (valve thrombosis in 2 and pannnus formation in 1). Orifice size of the implanted prosthesis (OS) as compared with the predicted normal size of the mitral valve (NS) was well correlated with maximum transprosthetic flow velocity estimated by Doppler echocardiography. In this study, the OS/NS>0.65 was maintained in all patients, and none required re-replacement because of prosthesis-patient mismatch. Conclusion: Patients less than 1 year of age had significant mortality and morbidity. The results were satisfactory in the remainder (1–3 years). During this follow-up period, none required re-replacement due to somatic growth, but it will be an unavoidable problem in the future. The OS/NS, which can be checked with a regular physical examination, may serve as a guide to determine the most appropriate timing for the second surgery.     

New Insights into Molecular Pathogenesis of Bone Marrow Failure in Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by the clonal expansion of hematopoietic stem cells with mutations of the phosphatidylinositol glycan-class A gene (PIGA). PNH clones then fail to generate glycosylphosphatidylinositol (GPI) or to express a series of GPI-linked membrane proteins including complement-regulatory proteins, resulting in complement-mediated intravascular hemolysis and thrombosis. Bone marrow failure is another characteristic feature of PNH. It is currently considered that immune-mediated injury of hematopoietic cells is implicated in PNH marrow failure as well as in aplastic anemia, a well-known PNH-related disorder. There is increasing evidence that the autoimmune attack allows PNH clones to selectively survive in the injured marrow, leading to clinical manifestations characteristic of PNH. As candidate molecules that trigger the immune attack on marrow cells, stress-inducible membrane proteins and Wilms’ tumor protein WT1 have been proposed. Among the stress-inducible proteins, GPI-linked proteins, such as cytomegalovirus glycoprotein UL16-binding protein, are distinct candidates that not only induce immune attack, but also allow PNH clones to survive the attack. Here, we overview the current understanding of the molecular pathogenesis of bone marrow failure in PNH.     

Primary epithelioid sarcoma of the vulva in pregnancy

Primary epithelioid sarcoma (ES) of the vulva is an extremely rare tumor, and to date, only 20 cases have been reported. We report the second case of vulvar ES presenting in pregnancy. A 25-year-old woman, at 6 weeks of gestation, was diagnosed as having vulvar sarcoma and was referred to our hospital. Immunohistochemical studies revealed that the tumor cells were positive for cytokeratin, epithelial membrane antigen (EMA), and wimentin. The tumor cells did not stain for S-100, SMA, HMB-45, desmin, LCA, CD-34, or estrogen and progesterone receptors. The tumor showed diffuse and strong staining for CD-117 (c-kit). After the curettage, she underwent local wide excision and left inguinal lymph node dissection and received external-beam radiation therapy. At 16 months of follow-up the patient was well without any disease recurrence. The appropriate treatment of vulvar ES is not clear, and the role of chemotherapy is disappointing; however, it might be worth investigating the role of Imatinib in c-kit overexpressing vulvar ES.     

Sesquiterpenes from <Emphasis Type="Italic">Curcuma comosa</Emphasis>

From the dried rhizomes of Curcuma comosa cultivating in Thailand, 26 known sesquiterpenes were isolated: zederone, zederone epoxide, furanodienone, isofuranodienone, 1(10)Z,4Z-furanodiene-6-one, glechomanolide, dehydrocurdione, neocurdione, curdione, 7α-hydroxyneocurdione, 7β-hydroxycurdione, germacrone-1(10),4-diepoxide, germacrone, 13-hydroxygermacrone, curzerenone, curcolonol, alismol, alismoxide, zedoarondiol, isozedoarondiol, procurcumenol, isoprocurcumenol, aerugidiol, zedoalactone B, curcumenone, and curcumadione. Their structures were elucidated on the basis of physicochemical evidence. Among them, glechomanolide, curzerenone, curcolonol, alismol, alismoxide, and zedoarondiol showed no significant optical activities, so they may be artifact products during the isolation or drying process.     

AP-1 (c-Fos/c-Jun) is required for corneal epithelial spreading

PURPOSE: We previously demonstrated that the AP-1 components c-fos/c-jun are up-regulated in healing rat corneal epithelium in a relatively early phase following epithelial débridement, implicating the AP-1 function in the initiation of cell movement. To explore this hypothesis, we examined the effect of lack of c-Fos and c-Jun protein expressions on the spreading of corneal epithelium and in situ in organ culture. Antisense-oligonucleotide (AS) c-fos-null mice were used for this purpose. METHODS: A rectangular piece of corneal tissue (2 x2 mm) was obtained from each eye of recently killed adult C57BL/6 mice and was incubated for 11 h in culture medium with 8 microM c-fos AS or c-jun AS probe. Sense probes were used for negative control. A rectangular section of corneal tissue was also obtained from each eye of c-fos(-/-), c-fos(+/-) and c-fos(+/+) mice and was organ-cultured for 11 h. The length of the path of epithelial spreading on stromal cut surface (both sides) was measured in hematoxylin-eosin-stained specimens. Data were analyzed by unpaired Student's t-test. RESULTS: Addition of c-fos AS to the medium decreased the length of epithelial spread to 40.36% of that in the control with the S probe. Addition of c-jun AS decreased the length of epithelial spreading rate to 42.71% of control with S probe. Lacking c-Fos decreased the epithelial spreading to 17.73% of control data from c-fos(+/-) and c-fos(+/+) mice. CONCLUSION: AP-1 (c-Fos/c-Jun) is required for the corneal epithelial spreading.     

Traditional and “new” cardiovascular risk markers and factors in pediatric dialysis patients

Cardiovascular disease (CVD) is the principal cause of mortality in patients with end-stage renal disease (ESRD). The aim of this study was to analyze carotid intima-media thickness (cIMT), endothelium-dependent dilatation (EDD), and left ventricular mass index (LVMI) as the cardiovascular risk markers and to investigate the independent risk factors of these markers in pediatric dialysis patients. This study included 39 children and adolescents undergoing dialysis (15 hemodialysis and 24 peritoneal dialysis) and 15 age- and gender-matched healthy subjects. The cIMT and EDD were assessed by high-resolution ultrasound, and LVMI was calculated from standard echocardiographic measurements. Compared with control subjects, cIMT standard deviation scores (SDS), LVMI, total homocysteine (tHcy), and high-sensitivity C-reactive protein (hs-CRP) values were significantly higher in patients, but EDD values did not differ. The mean hs-CRP level was significantly higher in hemodialysis (HD) patients than in peritoneal dialysis (PD) patients. The cIMT-SDS and LVMI were associated with several variables in univariate analysis. Stepwise linear regression analysis, indexed SBP (p = 0.017), and hemoglobin (p = 0.001) turned out to be independent variables for predicting LVMI, and a significant predictor of cIMT was indexed diastolic blood pressure (DBP) (p = 0.035). The causes of atherosclerosis and left ventricular hypertrophy are multifactorial in children and adolescents with ESRD. Better management of hypertension and anemia may be priorities for preventing or improving CVD in these patients.     

The Outcome of Gastrointestinal Stromal Tumors (GISTs) After a Surgical Resection in Our Institute

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract arising from Cajal's cells and expressing c-kit. In a consensus report, the clinical behavior of GISTs was categorized into risk classes according to the tumor size and mitotic count. We analyzed the risk categories based on GIST patients who underwent a surgical resection at our institute during a period of 15 years. METHODS: We evaluated the risk categories of GISTs and analyzed the outcome and risk categories retrospectively. We presented the MIB-1 score of the tumor instead of mitotic counts for the evaluation of cellular growth because of inaccuracies regarding the mitotic counts. RESULTS: Patients were classified into 4 cases of very low risk, 11 of low risk, 8 of intermediate risk, and 5 of high risk. Four high-risk patients showed recurrence as either liver metastasis or peritoneal dissemination. In addition, local recurrence occurred in one low-risk and one intermediate-risk patient each. CONCLUSION: Our cases confirmed the correlation between the risk categories and the prognosis. A complete resection with sufficient margin must be confirmed even in low-risk cases to prevent local recurrence. Since high-risk patients showed poor prognosis, the adjuvant treatment with chemotherapeutic regimens must therefore be further studied for high-risk patients.     

Disagreement between splenic switch-off and myocardial T1-mapping after caffeine intake

Caffeine is an adenosine receptor antagonist and a possible cause of inadequate stress perfusion. Splenic switch-off (SSO) and splenic rest-stress T1-mapping have been proposed as indicators of stress adequacy during perfusion cardiac magnetic resonance (CMR). We compared myocardial rest-stress T1-mapping with SSO and splenic rest-stress T1-mapping in patients with and without recent coffee intake. We analyzed 344 consecutive patients suspected of myocardial ischemia with adenosine perfusion CMR. All 146 normal CMR studies with a normal T1-rest of the myocardium, used as standard of reference, were included and divided in two groups. 22 patients accidentally ingested coffee <?4 h before CMR, compared to control group of 124 patients without self-reported coffee intake. Two independent readers graded SSO visually. T1-reactivity (ΔT1) was defined as percentual difference in T1-rest and T1-stress. Follow-up data were extracted from electronic patients records. In patients with recent coffee intake SSO was identified in 96%, which showed no significant difference with SSO in controls (94%, p?=?0.835), however event rates were significantly different (13.6 and 0.8%, respectively (p?<?0.001), median FU 17 months). Myocardial ΔT1 in the coffee group (??5.2%) was significantly lower compared to control (+?4.0%, p?<?0.001), in contrast to the splenic ΔT1 (??3.7 and ??4.0%, p?=?0.789). The splenic T1-mapping results failed to predict false negative results. SSO and splenic rest-stress T1-mapping are not reliable indicators of stress adequacy in patients with recent coffee intake. Therefore, the dark spleen sign does not indicate adequate myocardial stress in patients with recent caffeine intake. Myocardial rest-stress T1-mapping is an excellent indicator of stress adequacy during adenosine perfusion CMR.