Dose-related effects of direct hemoperfusion using a cytokine adsorbent column for the treatment of experimental endotoxemia

Objective To clarify the dose-related effects of direct hemoperfusion using a cytokine adsorbent column (CTR) on the mortality and inflammatory responses to endotoxin-induced shock in rats. Design Prospective and randomized study. Setting University research laboratory. Subjects Male Wistar rats. Interventions Forty-eight rats were injected intravenously with Escherichia coli endotoxin (15 mg/kg over 2 min), and then were randomly allocated to one of the following four groups (n = 12 per group): control group, treated without CTR for 120 min; quarter-dose treatment group, treated with CTR 0.25 ml for 120 min; half-dose treatment group, treated with CTR 0.50 ml; and full-dose treatment group, treated with CTR 1.0 ml. Measurements and results Hemodynamics and arterial blood gases were recorded, and mortality and plasma cytokine concentrations were calculated for the 8-h observation period. The mortality rates 8 h after endotoxin injection were 92%, 58%, 42% and 17% for the control column, quarter-dose, half-dose, and full-dose CTR groups, respectively. The increases in plasma cytokine concentrations were smaller in the half-dose and full-dose CTR treatment groups than in the endotoxemic group. Conclusions The present study showed that CTR treatment dose-dependently decreased the mortality rate and inhibited inflammatory responses in vivo. There was no supported funding in this study.     

Particle beam radiotherapy with a surgical spacer placement for unresectable sacral chordoma

Sacral chordomas constitute more than half of all chordomas and have a slower local growth than other bone malignant tumors. Although complete radical resection produces a longer local control and disease-free survival at the initial visit, chordomas are already often too large for complete resection to be possible. Particle radiotherapy consisting of proton and carbon-ion is a promising new modality which has an inherent anti-tumor effect against many types of malignancies. However, the application of particle radiotherapy for tumors adjacent to the gastrointestinal tract like sacral chordoma is restricted because the tolerance dose of the intestine is extremely low. A novel two-step treatment was developed with surgical spacer placement and subsequent proton radiotherapy to administer particle radiotherapy with curative intent. This report presents a case of a patient with a huge sacral chordoma treated by this method. This new strategy may potentially be an innovative and standard therapy for unresectable sacral chordoma in the near future.     

Inter/intra investigator variation in orchidometric measurements of testicular volume by ten investigators from five institutions

Aim： To perform quality control studies on testicular volume measurements for a multi-center epidemiological study of male reproductive function. Methods： We constructed a data matrix with a balanced assignment for 2 consecutive days by ten investigators （andrological career： 4-21 years） from five institutions and 12 male volunteers aged 20-26 years. Testicular volume was measured by Prader＇s orchidometer. A skilled technician also performed an ultrasound estimate of testicular volume. Results： A statistically significant inter-investigator variation was found for both testes （P 〈 0.05）. In addition, there was a statistically significant investigator-by-volunteer interaction in testicular volume measurement （P 〈 0.01）. However, there was no statistically significant difference in the two measurements performed on consecutive days for either testis. The testicular volumes for both the right and left testes as estimated by ultrasonography were smaller than results using the orchidometer. However, there was no statistical significance （P 〉 0.05）. The difference in experiences of the investigators did not significantly correlate with accuracy of measurements in either testis. Conclusion： The present study revealed significant differences in the results of estimation of testicular volume among the ten investigators, but intra-investigator variation was not considerable. Improved training and proper standardization of the measurement will be necessary before starting a multi-center study based on an andrological examination.     

Fluoroscopically guided epidural block in the thoracic and lumbar regions

BACKGROUND AND OBJECTIVES: Epidural block in the midthoracic region is difficult, even with fluoroscopically guided methods, because of the inability to view the interlaminar space on radiographs. We have, therefore, proposed fluoroscopically guided epidural block for the midthoracic region, as well as other thoracic and lumbar regions, by use of the pedicle as a landmark to show the height of the interlaminar space. METHODS: Twenty patients scheduled to receive an indwelling epidural catheter at Th6-7, Th9-10, Th12-L1, or L3-4 were studied. The skin insertion site was at the junction of a line parallel to the vertebral column that passed through the middle of the pedicle and the lower border of vertebral body, immediately inferior to the target interlaminar space on an anteroposterior radiograph. The needle was walked up the lamina, and the interlaminar space was sought near the midline of the vertebra at the height of the pedicle. RESULTS: Epidural block was easily performed in all cases. No difference was observed in the angulation of the epidural needle among the groups; the mean inward and upward angulation were 38 degrees and 63 degrees , respectively, although the skin insertion site relative to the spinous process was different among the groups. CONCLUSIONS: This study showed the usefulness of our fluoroscopically guided method for the midthoracic region, and other thoracic and lumbar regions. We propose an alternative method for a blind epidural approach at Th6-7, Th9-10, Th12-L1, or L3-4.     

Significance of glucose intolerance and SHIP2 expression in hepatocellular carcinoma patients with HCV infection

Glucose intolerance frequently is found in hepatocellular carcinoma (HCC) patients with hepatitis C virus (HCV) infection; however, the significance of glucose intolerance remains unclear. In addition, SH2 domain-containing inositol phosphatase (SHIP) 2 is a negative regulator of intracellular insulin signaling; however, changes in SHIP2 expression have not been investigated in HCC. To assess the significance of glucose intolerance, we analyzed 118 HCC patients with HCV infection. Twenty HCC specimens were used for immunoblotting and immunostaining for SHIP2. Patients were classified into two groups: a glucose intolerance group (n=39) and a normal glucose tolerance group (n=79). There was no significant difference in the disease-free survival (P=0.838) or long-term survival (P=0.091) between the groups. However, for males, the cumulative survival rate was significantly lower in the glucose intolerance group (n=22) than that in the normal glucose tolerance group (n=52) (P=0.036). In multivariate analysis, Child-Pugh class (P=0.0003) and glucose intolerance (P=0.036) were identified as statistically significant and independent prognostic factors in males. SHIP2 expression level decreased in HCC compared to that in nontumor tissues. In conclusion, this study is the first to demonstrate the significance of glucose intolerance in prognosis of male HCC patients and down-regulation of SHIP2 expression in HCC.     

Suppression of inflammatory cell recruitment by histamine receptor stimulation in ischemic rat brains

Inflammation is a crucial factor in the development of ischemia-induced brain injury. Since facilitation of central histaminergic activity ameliorates reperfusion injury, effects of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H3 receptor antagonist, on inflammatory cell infiltration were evaluated in a rat model of transient occlusion of the middle cerebral artery. After reperfusion for 12, 24, or 72 h following 2 h of occlusion, brain slices were immunohistochemically stained with antibodies against myeloperoxidase and CD68, which were markers of polymorphonuclear leukocytes and macrophages/microglia, respectively. After reperfusion for 12-24 h, the number of neutrophils on the ischemic side increased markedly, whereas the increase was not observed on the contralateral side. Administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the number of neutrophils to 52%. Simultaneous administration of thioperamide (5 mg/kg, s.c.) further decreased the number of neutrophils to 32%. Likewise, the ischemia induced increase in the number of CD68-positive cells after 24 h was suppressed by L-histidine injections. The L-histidine administration decreased the number of CD4+ T lymphocytes on both ischemic and contralateral sides after 12 h, and concurrent administration of thioperamide prolonged the effect. Although administration of mepyramine (3 nmol, i.c.v.) did not affect suppression of leukocyte infiltration, ranitidine tended to reverse the effect of L-histidine. These data suggest that enhancement of central histaminergic activity suppresses inflammatory cell recruitment after ischemic events through histamine H2 receptors, which may be a mechanism underlying the protective effect of L-histidine.     

Analysis of national representative opinion surveys concerning gestational surrogacy in Japan

OBJECTIVE: Although gestational surrogacy offers several advantages, this procedure has given rise to some ethical and legal issues. We aimed to clarify the factors affecting the attitude of the Japanese toward gestational surrogacy. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Nationwide opinion surveys concerning assisted reproductive technologies (ART) were carried out in 1999 and 2003. Participants included 2568 and 3647 people from the general public surveyed in 1999 and 2003, respectively (1564 people received only the questionnaire, and 2083 people received a questionnaire and brochure about ART). MAIN OUTCOME MEASURE: Multivariate-adjusted odds ratio and 95% confidence interval from logistic regression models for factors affecting the attitude toward gestational surrogacy. RESULTS: In both surveys, approximately half of respondents approved of gestational surrogacy; 20-30% disapproved of the procedure. People with high socioeconomic status clearly expressed their opinion on this issue. A liberal attitude toward gender role promoted approval of gestational surrogacy; a liberal attitude toward family had the opposite effect. CONCLUSION: Our findings suggest that socioeconomic status affects people's expression of their opinion regarding this issue, while attitudes toward this procedure were influenced by individual belief. Considering socioeconomic status and diversity of individual belief is required for further discussion on this topic.     

Prognostic factors for ovulatory response with clomiphene citrate in polycystic ovary syndrome

OBJECTIVE: To evaluate prospectively the prognostic factors for ovulatory responses following clomiphene citrate (CC) administration in polycystic ovary syndrome (PCOS). STUDY DESIGN: Fifty-nine infertile patients with a diagnosis of PCOS were recruited. Ovulation was induced using 100 mg/day CC administered daily from days 5 to 9 of the cycle. Endocrine and metabolic parameters between responder and non-responder groups were analyzed. RESULTS: For a 75-g fasting glucose load (75-g OGTT), blood glucose levels at 60 and 120 min, the area under the curve (AUC) and blood insulin levels at 120 min in the non-responder group (n=25) were significantly higher than those in the responder group (n=34), although the measurements of fasting blood glucose and insulin were not significantly different between the two groups. In the receiver operating characteristic curves, the most appropriate cutoff point was 120 mg/dl for the blood glucose level at 120 min and 9000 for the blood glucose x insulin level at 120 min. There were no significant differences in the clinical characteristics or in the endocrine and metabolic parameters between conceived (n=9) and non-conceived groups (n=21). CONCLUSION: The levels of blood glucose and blood glucose x insulin at 120 min after 75-g OGTT could be good biochemical markers of CC resistance in PCOS. No predictors of conception following CC therapy were identified by this study.     

Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis

We found cotransactivation of cell division associated 1 (CDCA1) and kinetochore associated 2 (KNTC2), members of the evolutionarily conserved centromere protein complex, in non-small cell lung carcinomas (NSCLC). Immunohistochemical analysis using lung cancer tissue microarray confirmed high levels of CDCA1 and KNTC2 proteins in the great majority of lung cancers of various histologic types. Their elevated expressions were associated with poorer prognosis of NSCLC patients. Knockdown of either CDCA1 or KNTC2 expression with small interfering RNA significantly suppressed growth of NSCLC cells. Furthermore, inhibition of their binding by a cell-permeable peptide carrying the CDCA1-derived 19-amino-acid peptide (11R-CDCA1(398-416)) that correspond to the binding domain to KNTC2 effectively suppressed growth of NSCLC cells. As our data imply that human CDCA1 and KNTC2 seem to fall in the category of cancer-testis antigens, and that their simultaneous up-regulation is a frequent and important feature of cell growth/survival of lung cancer, selective suppression of CDCA1 or KNTC2 activity and/or inhibition of the CDCA1-KNTC2 complex formation could be a promising therapeutic target for treatment of lung cancers.