Efficacy and Bleeding Risk of Antithrombin Supplementation in Patients With Septic Disseminated Intravascular Coagulation: A Third Survey.

INTRODUCTION: Although recent studies have reported the efficacy of antithrombin (AT) supplementation for sepsis-associated disseminated intravascular coagulation (DIC), the factors that influence AT's effect have not been sufficiently studied. The purpose of this survey was to identify factors that modulate the effects and the adverse effects of AT. METHODS: We performed a multi-institutional survey. The data from 159 patients with septic DIC with AT ≤70% and who had undergone AT supplementation were analyzed. The patients' demographic characteristics, including the infection site, baseline sepsis-related organ failure assessment (SOFA) score, baseline DIC score, and baseline AT activity, were analyzed in relation to the 28-day mortality. Bleeding-related adverse events were also examined. RESULTS: Overall, 116 patients survived and 43 did not (28-day mortality: 27.0%). A logistic regression analysis revealed that the baseline SOFA score (odds ratio [OR]: 0.816, P = .001), coadministration of recombinant thrombomodulin (rTM; OR: 3.989, P = .006), and respiratory tract infection (OR: 0.129, P = .000) were significantly associated with the survival. Survivors exhibited a higher peak AT activity than nonsurvivors (85.1% vs 65.0%, P = .027). Bleeding events were observed in 4.13% (major bleeding: 1.65%) of the patients, and the coadministration of rTM did not increase the risk of bleeding (with rTM: 4.11% vs without rTM: 4.17%). Heparin was concomitantly used in 22 (18.2%) cases, and its use nonsignificantly increased the bleeding risk (with heparins: 9.09% vs without heparins: 3.03%; P = .224). CONCLUSION: The coadministration of rTM may improve survival without increasing the risk of bleeding in patients with sepsis-associated DIC treated with AT.

Blood pressure measured in the clinic and at home during pregnancy among nulliparous and multiparous women: the BOSHI study.

BACKGROUND: Hypertension during pregnancy can cause serious problems during delivery, such as stroke, premature delivery, or low birthweight. Nulliparity is believed to be a risk factor for hypertension during pregnancy. However, the relationship between parity and blood pressure determined at home during pregnancy is still unknown. METHODS: We assessed the incidence of gestational hypertension or preeclampsia in 575 nulliparous and multiparous women. Also, we examined blood pressure measured in the clinic and at home among 530 normotensive pregnant women who received antenatal care at a maternity hospital in Japan. Clinic blood pressures (CBPs) were obtained by duplicate measurement at each antenatal care visit. The participants were also required to measure their own blood pressures every morning at home while they were pregnant. A linear mixed model was used for analysis of the blood pressure course throughout pregnancy. RESULTS: A total of 315 nulliparous and 215 multiparous women were entered into this study (mean age, 30.1 ± 4.6 years and 33.0 ± 4.1 years, respectively). CBP levels during pregnancy among nulliparous women were significantly higher than among multiparous women (P = 0.02/P <0.0001 for systolic/diastolic blood pressure), whereas there were no significant differences in home blood pressure (HBP) levels during pregnancy between the two groups (P = 0.4/P = 0.2 for systolic/diastolic blood pressure). CONCLUSIONS: HBP levels during pregnancy were shown not to differ between nulliparous and multiparous women, while CBP levels during pregnancy were higher among nulliparous than among multiparous women.

Daily serial hemodynamic data during pregnancy and seasonal variation: the BOSHI study.

Although there are some reports that low plasma volume or increased cardiac output is associated with developing preeclampsia, there are few reports of daily serial hemodynamic data during pregnancy. A total of 37,092 home blood pressure (BP) and heart rate (HR) measurements were obtained from 425 normal pregnant women. Heart rate and shock index (SI) gradually increased by gestational week 32 and then decreased, whereas double product (DP) increased linearly during pregnancy. Although systolic BP and DP were consistently and negatively correlated with daily minimum outside temperature, HR and SI were positively correlated with minimum outside temperature in summer.

Environmental factors and seasonal influenza onset in Okayama city, Japan: case-crossover study.

Seasonal influenza infection is a major challenge in public health. The term "seasonal influenza" refers to the typical increase in the number of influenza patients in the winter season in temperature zones. However, it is not clear how environmental factors within a single flu season affect influenza infection in a human population. Therefore, we evaluated the effects of temperature and humidity in the 2006-7 flu season on the onset of seasonal influenza using a case-crossover study. We targeted patients who attended one pediatric clinic in Okayama city, Japan and who were diagnosed as being infected with the seasonal influenza virus. Using 2 references (time-stratified and symmetric bidirectional design), we estimated the effects of average temperature and relative humidity from the onset day (lag0) to 10 days before (lag10). The total number of subjects was 419, and their onset days ranged from 26 December 2006 to 30 April 2007. While the onset was significantly associated with lower temperature, relative humidity was not related. In particular, temperatures before the 3-day incubation period had higher-magnitude odds ratios. For example, the odds ratio and 95% confidence interval for average temperature at time lag 8 was 1.12 (1.08-1.17) per 1.0℃ decrease. Low environmental temperature significantly increased the risk of seasonal influenza onset within the 2006-7 winter season.

Seasonal trends of blood pressure during pregnancy in Japan: the babies and their parents' longitudinal observation in Suzuki Memorial Hospital in Intrauterine Period study.

OBJECTIVE: Blood pressure (BP) increases both in winter and in the last trimester of pregnancy. Some interaction seems to exist between season and gestational age. The present study observed home BP values during pregnancy with adjustment for seasonal variation and gestational age. METHODS: We observed 10353 home BP measurements from 101 normal pregnant women attending a maternity hospital in Japan. Home BP values were examined by mixed linear model adjusting for meteorological data and gestational age. RESULTS: The lowest home BP values were observed in the second trimester [mean (+/-standard deviation) systolic/diastolic BP, 101.8 +/- 7.9/59.8 +/- 5.8 mmHg at gestational week 20]. In the last trimester, home BP values gradually increased and the values after gestational week 26 were significantly higher than those at gestational week 20 (110.1 +/- 9.7/66.8 +/- 7.7 mmHg at gestational week 40). A 10 degrees C increase in daily minimum outdoor temperature was associated with a mean reduction of 2.5/2.5 mmHg (Delta systolic BP/Delta diastolic BP: 95% confidence interval, 2.3/2.4 to 2.6/2.7 mmHg) in home BP with adjustment for gestational age. The largest and smallest estimated home BP changes during pregnancy were 12.8/12.5 and 3.1/3.0 mmHg in pregnant woman who delivered in January and July, respectively. CONCLUSION: Interactions among BP, season and gestational age should be considered when evaluating BP in pregnant women. Risks associated with high BP might be underestimated in pregnant woman in summer who will deliver in winter.

Rapid speciation analysis of Cr(VI) and Cr(III) by reversed-phase high-performance liquid chromatography with UV detection.

A simple and rapid method is developed for the simultaneous determination of Cr(VI) and Cr(III) based on the formation of their different complexes with ammonium pyrrolidine-dithiocarbamate (APDC). Separation is performed using reversed-phase high-performance liquid chromatography coupled with UV detection. The conditions for complex formation and speciation are determined, such as solution pH, amount of APDC, temperature, and type of mobile phase. In order to substantially reduce the analysis time, the separation is carried out without extraction of chromium-APDC complexes from the mother liquor. Under the optimum analysis conditions, the chromatograms obtained show good peak separation, and the absolute detection limits (3s) are 2.2 microg/L for Cr(VI) and 4.5 microg/L for Cr(III). The calibration curves are linear from 3 to 5000 microg/L for Cr(VI) and 5 to 3000 microg/L for Cr(III). The relative standard deviations of peak areas in five measurements using a sample solution of 200 microg/L are less than 2% for Cr(VI) and 4% for Cr(III), indicating good reproducibility for this analytical method. Furthermore, simultaneous determination of Cr(VI) and Cr(III) is successful with the application of the proposed procedure in the synthetic wastewaters containing common heavy metal ions: Fe(III), Pb(II), Cd(II), Cu(II), and Zn(II).

Echigo-1: a panencephalopathic strain of creutzfeldt-jakob disease. I. neuropathological and immunohistochemical studies.

We demonstrate an unusually intensive accumulation of prion protein (PrP) on neuronal membranes in hamsters infected with the Echigo-1 panencephalopathic strain of Creutzfeldt-Jakob disease. This stands in strong contrast with the poor vacuolation in this model. Several distinct patterns of PrP(TSE) deposit were observed in the brain. The first type consisted of a fine granular "synaptic"/diffuse type of accumulation which, especially in the cerebral cortex, appeared laminar. Deposits frequently coalesced to form plaque-like structures. The second pattern consisted of perivascular plaque-like accumulations. When a vessel was cut longitudinally, these formed long linear arrays of plaques and smaller globules. The third, and most striking, consisted of perineuronal deposits. These formed small dots and coarser globules which were densely situated on the neuronal membrane on both cell bodies and their processes.

Echigo-1: a panencephalopathic strain of Creutzfeldt-Jakob disease. II. Ultrastructural studies in hamsters.

In this and a companion paper we present immunohistochemical and ultrastructural data on hamsters infected with the Echigo-1 strain of Creutzfeldt-Jakob disease. Ultrastructurally, two types of vacuoles were readily discriminated in the brain: the grey matter vacuoles of spongiform change and intramyelin vacuoles. The vacuoles were always membrane-bound; the membranes were single or double. The axons were entirely missing from the plane of the sections or, if visible, were shrunken and attached to the innermost layer of the myelin. It was noteworthy that some vacuoles indented cell bodies or processes and thus were reminiscent of the intraneuronal vacuoles typical for natural scrapie, BSE and CWD in ungulates and cervids but not of the vacuoles encountered in rodent models of scrapie and CJD. We also noticed vacuoles distending myelinated fibres in which the axons had become dystrophic. Some axons underwent Wallerian degeneration while others met the criteria for dystrophic neuritis. Both alterations existed in the same areas. Typical dystrophic neurites contained abnormal subcellular organelles, mainly electron-dense lysosomal inclusions. Other neurites contained numerous multi-vesicular bodies and autophagic vacuoles. Nuclear paracrystalline rod-like inclusions were occasionally visible in neurons while other inclusions comprised spiroplasma-like inclusions in synaptic boutons. The robust cellular reactions consisted of reactive astrocytes and macrophages filled with cellular debris. It is of note that complex autophagic vacuoles were observed in the cytoplasm of neurons.

Prediction of 5-fluorouracil and cisplatin synergism for advanced gastrointestinal cancers using a collagen gel droplet embedded culture.

PURPOSE: The combination effects of 5-fluorouracil (5-FU) and cisplatin (CDDP) are herein reported using a drug sensitivity assay, with a special focus on the induction of apoptosis. METHODS: The combination effects of 5-FU and CDDP were examined using in vitro chemosensitivity testing by means of the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in MKN45 and GSS cell lines, and primary gastrointestinal cancer cells ob-tained from 40 patients. Apoptosis was assayed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin neck end labeling (TUNEL) method. RESULTS: The combination of 5-FU with CDDP increased the efficacy of 5-FU 1.16-1.35-fold with the GSS cell line and 1.10-2.01-fold with primary gastric and colorectal cancers when the exposure time was 7 days. In primary tumor cells a synergistic action was noted in 15 of 40 (38%) gastric and colorectal cancers. Both 5-FU and CDDP were found to induce apoptosis in GSS and MKN45 cells, and the number of apoptotic cells increased synergistically after the combined treatment in the GSS cases and showed a correlation with the results of CD-DST. CONCLUSIONS: Our findings suggested that the efficacy of the combined treatment with 5-FU and CDDP can be predicted by the in vitro chemosensitivity test and that a synergistic effect might be associated with the induction of apoptosis.