Optimal administration dosage of magnesium sulfate for torsades de pointes in children with long QT syndrome

BACKGROUND: Intravenous administration of magnesium sulphate (MgSO(4)) is a very effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. Discussed here is the efficacy of MgSO(4) for TdP in children with congenital and acquired LQTS. METHODS: The optimal MgSO(4) dosage and serum magnesium (SMg) was determined in six consecutive children with TdP; four had congenital LQTS and two had acquired LQTS. A bolus injection of MgSO(4) was given intravenously over 1 to 2 minutes followed by continuous infusion for the next 2 to 7 days. RESULTS: Of the six patients, five responded completely to the initial bolus of 6.1 +/- 4.2 mg/kg (range, 2.3-12 mg/kg). One (a neonate with congenital LQTS) required a total of 30 mg/kg until complete TdP elimination. Continuous infusion was given at rates of 0.3 to 1.0 mg/kg/hr with no recurrence of TdP. SMg concentration was 3.9 +/- 1.0 mg/dL (2.9-5.4 mg/dL) immediately after bolus injection. CONCLUSION: Intravenous MgSO(4) infusion effectively treated TdP in children with LQTS. Optimal bolus dosage, infusion rates and SMg concentration were 3 to 12 mg/kg, 0.5 to 1.0 mg/kg/hr and 3 to 5 mg/dL, respectively.     

Mechanism of carcinogenesis in familial tumors

It is thought that malignant tumors occur through interactions of multiple environmental factors and a personal genetic factor. A normal somatic cell having an intrinsic function is able to acquire the characteristics of a malignant cell under the influence of many factors. A small percentage of all tumors have obvious familial aggregation. These entities are called familial cancer. The familial cancer syndrome is well defined for colorectal cancer, breast cancer, endocrine neoplasia, and so on. Traits of familial tumors are sequentially inherited by offspring through gametes in a Mendelian fashion, most commonly in an autosomal-dominant manner. Carcinogenesis requires multiple genetic events. A patient with a familial tumor is ahead of an individual without any germline mutation in the carcinogenesis process. In such a situation, patients frequently suffer from multiple malignant tumors at a young age. It is well known that three major genes are closely related to the cell cycle and tumorigenesis. These gene types are protooncogenes, tumor suppressor genes, and DNA mismatch repair genes. Proto-oncogenes function to accelerate cells during the G₁ or growth phase of the cell cycle. Tumor suppressor genes act as blocks against cell growth and proliferation. Inactivation of tumor suppressor genes requires alterations in both alleles. These phenomena are known as Knudsons two-hits theory. However, DNA mismatch repair genes are known as caretaker genes and correct mismatch pair generation during DNA replication. Germline mutation of DNA mismatch repair genes causes hereditary nonpolyposis colorectal cancer. The tumor phenotype from patients with hereditary nonpolyposis colorectal cancer is demonstrated to be microsatellite instability positive.     

Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma

Background Interleukin-18 (IL-18), a cytokine produced by macrophages, is capable of inducing T-lymphocyte synthesis of interferon- (IFN-). In this study, for the first time, the serum concentration of IL-18 and its significance as a prognostic indicator was evaluated in patients with epithelial ovarian cancer.Methods The serum IL-18 level was measured by an enzyme-linked immunosorbent assay (ELISA) in 69 patients with epithelial ovarian cancer and 8 healthy controls. Relationships between the IL-18 level and clinicopathological features were examined by univariate and multivariate analyses.Results The median serum IL-18 level in the ovarian cancer patients was 229.6pg/ml, and the level was significantly elevated compared with that in the normal controls (151.3pg/ml; P 0.01). No significant correlations were detected between the IL-18 level and stage or histology (P = 0.08 and P = 0.12, respectively). On univariate analysis, overall survival was shown to be affected by IL-18 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-18 serum levels, while confirming the role of previously established prognostic variables, such as performance status, stage, and residual tumor.Conclusion This study showed that IL-18 serum levels were elevated in ovarian cancer patients and were correlated with overall survival, although they were shown not to be an independent prognostic factor.     

Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.     

Isolation and characterization of the stage-specific cytochrome b small subunit (CybS) of Ascaris suum complex II from the aerobic respiratory chain of larval mitochondria

We recently reported that Ascaris suum mitochondria express stage-specific isoforms of complex II: the flavoprotein subunit and the small subunit of cytochrome b (CybS) of the larval complex II differ from those of adult enzyme, while two complex IIs share a common iron-sulfur cluster subunit (Ip). In the present study, A. suum larval complex II was highly purified to characterize the larval cytochrome b subunits in more detail. Peptide mass fingerprinting and N-terminal amino acid sequencing showed that the larval and adult cytochrome b (CybL) proteins are identical. In contrast, cDNA sequences revealed that the small subunit of larval cytochrome b (CybS(L)) is distinct from the adult CybS (CybS(A)). Furthermore, Northern analysis and immunoblotting showed stage-specific expression of CybS(L) and CybS(A) in larval and adult mitochondria, respectively. Enzymatic assays revealed that the ratio of rhodoquinol-fumarate reductase (RQFR) to succinate-ubiquinone reductase (SQR) activities and the K(m) values for quinones are almost identical for the adult and larval complex IIs, but that the fumarate reductase (FRD) activity is higher for the adult form than for the larval form. These results indicate that the adult and larval A. suum complex IIs have different properties than the complex II of the mammalian host and that the larval complex II is able to function as a RQFR. Such RQFR activity of the larval complex II would be essential for rapid adaptation to the dramatic change of oxygen availability during infection of the host.     

Comparison of body size and composition between young adult Japanese-Americans and Japanese nationals in the 1980s

BACKGROUND: Data on body composition of American-born Japanese (Japanese-Americans) are scarce. Studies on differences of body composition between Japanese-Americans and Japanese nationals at various stages of life as well as at various times of measurements are useful for understanding the impact of lifestyle changes on body composition in the two societies. AIM: To see the differences in body size and composition between young adult Japanese-Americans and Japanese nationals. SUBJECTS AND METHODS: Body size and composition of 50 Japanese-Americans consisting of 28 males and 22 females ranging in age from 18 to 23 years were compared with Japanese nationals matched for age and height. Body composition was measured using the underwater weighing method. The study was conducted in the 1980s in the USA and Japan. RESULTS: The average percentage body fat of males was 13.7% for both Japanese-Americans and Japanese nationals, and that of females was approximately 24% for both groups, even though Japanese-American males and females had significantly greater body weight, fat-free mass, and body mass index than Japanese nationals. CONCLUSION: Although young adult Japanese-Americans showed larger body size than Japanese nationals, their percentage fat did not differ at this stage of life in the 1980s.     

Effect of luminance on perception of gaze direction in Japanese

When the luminance of one side of the sclera is darkened artificially, the perceived direction of gaze biases toward the darker side of the sclera. This gaze effect was measured in photographic and schematic images of eyes using Japanese subjects. The effect was larger than previous results: the gaze shift induced by luminance reached 40 deg of gaze or more. The luminance of the iris also affected the results. The effect of scleral darkening was compared to the gaze shift induced by an actual shift of the iris. The results suggest that one mechanism for gaze judgment is based on low-level analysis of the luminance configuration within the eye. This effect might appear to be large in Japanese subject because of their equally dark iris.     

Management of missed abortion in a patient with congenital cervical atresia

OBJECTIVE: To describe a patient with congenital cervical atresia who became pregnant through IVF and thawed transmyometrial ET and then experienced a missed abortion. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A patient with congenital cervical atresia who underwent reconstructive surgery at 23 years of age and underwent IVF twice at 28 and 30 years of age. INTERVENTION(S): Abortion management. MAIN OUTCOME MEASURE(S): Medical follow-up of IVF-ET, resultant pregnancy, and abortion. RESULT(S): After the second cycle of IVF with frozen-thawed transmyometrial ET, the patient became pregnant but then experienced a missed abortion. Serum beta-hCG levels decreased, the two gestational sacs disappeared, and genital bleeding without signs of infection occurred 14 weeks after diagnosis of the abortion. The abortion was managed conservatively. CONCLUSION(S): When assisted reproductive techniques are used in patients with congenital cervical atresia, the risks (including those relating to the management of an abortion) should be explained in detail to the couple and sufficient informed consent should be obtained before starting IVF-ET procedures.     

Interleukin-13 induces goblet cell differentiation in primary cell culture from Guinea pig tracheal epithelium

The Th2 cytokines, interleukin (IL)-4 and IL-13, bind to IL-4Ralpha, and cause goblet cell metaplasia/hyperplasia with increased mucin expression in vivo. However, there is not enough evidence that these cytokines directly induce mucin production in vitro. In this study, primary epithelial cells from guinea pig trachea were cultured at an air-liquid interface, and immediately after achieving confluence at Day 7 they were treated with human recombinant IL-4 or IL-13 for 14 d. IL-13-treated cells consisted of a large number of fully mature goblet cells with a smaller number of ciliated cells. Secretory granules of the goblet cells were positive for both periodic acid-Schiff and toluidine blue, and showed exocytosis. By contrast, IL-4 failed to induce goblet cell differentiation. The electric resistances of IL-13-treated cells were lower than those of IL-4-treated cells and nontreated cells, suggesting leaky epithelia. MUC5AC protein level in cell lysates measured by ELISA was several-fold higher in IL-13-treated cells than in nontreated cells, whereas the level in IL-4-treated cells was not changed. These data suggest that human recombinant IL-13, but not IL-4, can induce differentiation into mature goblet cells that produce MUC5AC protein in guinea pig tracheal epithelial cells in vitro.