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Objective: To test whether early blood administration combined with crystalloid solution infusion may prolong survival in a clinically relevant model of ongoing uncontrolled life-threatening hemorrhage., Methods: Light anesthesia was induced with halothane in 24 rats, and spontaneous breathing was maintained. Uncontrolled hemorrhagic shock was induced by withdrawal of blood at 2.5 mL/100 g over a 15-minute period, followed by 75% tail amputation. At 10 minutes after tail cutting, rats were randomized into four groups (n = 6 each): group 1, receiving 3 mL of shed blood for 5 minutes followed by 9 mL of lactated Ringer's (LR) solution for 15 minutes; group 2, receiving 9 mL of LR solution for 15 minutes followed by 3 mL of shed blood for 5 minutes; group 3, receiving 9 mL of LR solution only for 15 minutes; group 4, receiving neither of shed blood nor LR solution. Rats were then observed until death or a maximum of 180 minutes., Result: Mean survival time was 138 +/- 30 minutes, 108 +/- 22 minutes, 79 +/- 13 minutes, and 55 +/- 18 minutes for groups 1, 2, 3, and 4, respectively (p < 0.05 among the four groups). Additional blood loss from the tail stump did not differ significantly between the three treatment groups., Conclusions: In a model of uncontrolled hemorrhagic shock in rats, a resuscitation regimen using crystalloids agent alone is not ideal, and even a brief delay in blood administration worsens survival. Early blood administration combined with crystalloid solution infusion seems ideal.

This study examined the cerebral functional lateralization, from a phonological perspective, in children with autism spectrum disorder (ASD) and typically developing children (TDC). With near infrared spectroscopy, we measured auditory evoked-responses in the temporal areas to phonemic and prosodic contrasts in word contexts. The results of TDC showed stronger left-dominant and right-dominant responses to phonemic and prosodic differences, respectively. Furthermore, although ASD children displayed similar tendencies, the functional asymmetry for phonemic changes was relatively weak, suggesting less-specialized left-brain functions. The typical asymmetry for the prosodic condition was further discussed in terms of acoustic-physical perceptual ability of ASD children. The study revealed differential neural recruitment in decoding phonetic cues between ASD children and TDC and verified the applicability of near infrared spectroscopy as a suitable neuroimaging method for children with developmental disorders.

Near-infrared spectroscopy was used to measure hemodynamic responses in Korean subjects learning Japanese as a second-language to Japanese phonemic contrasts that are either phonologically distinctive or non-distinctive in their first-language. These results were compared with those of Japanese native listeners reported previously. Unlike the results observed in the Japanese subjects, the Korean subjects did not show category-specific neural responses to a durational contrast that is non-distinctive in their first-language. The /a-e/ contrast elicited the larger response in the left auditory area, consistent with the results of the Japanese. These phoneme-dependent responses imply that the neuronal networks subserving the first and second-languages are either shared or exclusive according to the mutual relationship between the phonemic properties of the first and second-languages.

The present study examined cerebral representations of Japanese long and short vowel categories with near-infrared spectroscopy (NIRS) by measuring the hemodynamic changes. Results showed that NIRS could capture phoneme-specific information. The left side of the auditory area showed large hemodynamic changes only for contrasting stimuli between which the phonemic boundary was estimated, but not for stimuli differing by an equal duration but belonging to the same phoneme category. Left dominance in phoneme processing was also confirmed for the across-category stimuli. These findings indicate that the Japanese vowel contrast based only on duration differences is dealt with in the same language-dominant hemisphere as other spectrally varying phonemic categories, and that the cortical activities related to its processing can be detected with NIRS.

The aim of this study was to determine the significance of bowel resection in advanced ovarian cancer. A total of 64 women with stage IIIc or IV epithelial ovarian cancer, who consecutively received primary treatment between 1991 and 1995, were entered in this prospective study. The outcome of the patients undergoing bowel resection was evaluated. Thirty-nine patients underwent cytoreductive surgery at initial surgery. Of them, 16 patients could undergo optimal operation without bowel resection. Twenty-three patients received bowel resection at initial surgery. Of these 23 patients, 16 underwent optimal operation and 7 did not. Among 25 patients judged as inoperable cases at initial surgery, 21 responded to chemotherapy and underwent second surgery. Of 21 patients receiving second surgery, 15 underwent optimal operation (7 without bowel resection and 8 with bowel resection). The 3-year survival rate for 24 patients undergoing optimal operation with bowel resection (46.8%) was not significantly different from that for 23 patients without bowel resection (59.1%). Postoperative complications were seen in 8 patients (21.6%) of the patients receiving bowel resection and 3 (13.0%) of those without bowel resection. Cytoreductive surgery including bowel resection is effective for an improvement of the survival in patients with advanced ovarian cancer, if an optimal operation can be performed.

Objective: To assess telomerase activity associated with the development and extension of epithelial ovarian cancer and to investigate the relationship between p53 gene status and telomerase activity., Methods: A total of 53 samples (41 epithelial ovarian cancers, five borderline epithelial tumors, four benign adenomas, and three surface epithelia) were examined for telomerase activity by the polymerase chain reaction (PCR) -based telomeric repeat amplification protocol assay. Mutations in the p53 gene were determined by PCR-single strand conformation polymorphism analysis., Results: Telomerase activity was detected in 33 of 41 epithelial ovarian cancers and in three of five borderline malignancies but was not detectable in either benign tumors or normal surface epithelium. The mean (+/-standard deviation [SD]) intensity of telomerase activity in cancers was significantly higher than that in borderline malignancies (10.6+/-8.2 versus 3.6 4+/-1.3). The positivity of telomerase activity did not correlate with any clinical findings, but the intensity (+/-SD) of telomerase activity was significantly higher in tumors with lymph node involvement (12.2+/-8.3 versus 3.8+/-1.1). Mutations of the p53 gene were observed in 44% of ovarian cancers; p53 gene status did not relate to telomerase activity. Multivariate analysis showed that the intensity of telomerase activity was not an independent factor for prognosis of patients with ovarian cancer., Conclusion: Telomerase activity may be associated with development and extension of epithelial ovarian cancer.

Objective: To compare three platinum compounds for their antitumor effects on cervical cancer after systemic and intra-arterial infusion., Methods: Adult female rabbits with squamous cell carcinoma of the uterine cervix received infusions of 1.7 mg/kg cisplatin, 10 mg/kg carboplatin, or 6 mg/kg cis-diammine (glycolato)platinum (254-S) via the internal iliac artery or ear vein. Platinum concentrations in the tumor and tumor size were measured after internal iliac arterial or intravenous (i.v.) infusion with these platinum compounds., Results: The platinum concentration in the tumor after intra-arterial infusion was significantly higher than that after i.v. infusion for cisplatin. However, the tumor concentrations of platinum for carboplatin and 254-S did not differ between the infusion methods. The platinum concentration 20 minutes after i.v. infusion was significantly higher for 254-S than for cisplatin or carboplatin. The platinum concentration 7 days after intra-arterial infusion was significantly higher with cisplatin than with carboplatin or 254-S. Tumor size 7 days after intra-arterial infusion was significantly smaller than that after i.v. infusion for cisplatin (1.85 +/- 0.54 versus 5.60 +/- 2.60 cm2; P < .05). Tumor size was significantly smaller with 254-S than with cisplatin or carboplatin using the i.v. infusion method (2.40 +/- 0.21 cm2 for 254-S, 5.60 +/- 2.60 cm2 for cisplatin, and 5.13 +/- 1.59 cm2 for carboplatin, P < .05., Conclusions: Intra-arterial infusion seems to be a suitable route of administration for cisplatin, whereas i.v. infusion appears to have an advantage for 254-S in the treatment of cervical cancer.

To clarify the effect of neoadjuvant intraarterial infusion chemotherapy on the cure rate in advanced cervical cancer with bulky tumor, a total of 50 patients were examined prospectively. The clinical stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification included 23 IIb, 6 IIIa, and 21 IIIb. These patients were randomly divided into the neoadjuvant intraarterial infusion chemotherapy group and the control group. There were no significant differences in mean age, FIGO clinical stage, and tumor histology between groups. Twenty-five patients in the former group were given 25 mg/m2 of cisplatin and 15 mg/m2 of bleomycin via each internal iliac artery. If the results of the evaluation indicated that surgery was feasible, radical surgery was performed. The patients whose tumors were inoperable received radiation therapy consisting of external irradiation and intracavitary irradiation. Twenty-five patients in the control group also underwent the same radiation therapy. The overall response rate was 80.0%. Eighteen of 20 responders underwent surgery. The 3-year survival rate was 85.7% for operated patients, 42.9% for patients receiving neoadjuvant intraarterial infusion chemotherapy followed by irradiation, and 49.5% for the control group. In the present study, neoadjuvant intraarterial infusion chemotherapy did not improve the prognosis of patients with advanced cervical cancer compared to radiation therapy alone, and only responders who underwent surgery obtained an advantage in survival.

Objective: To compare three platinum compounds, and study the pharmacokinetics of these compounds after systemic and intra-arterial infusion., Methods: Adult female rabbits received infusions of 1.7 mg/kg cisplatin, 10 mg/kg carboplatin, or 6 mg/kg cisdiammine(glycolato)platinum (254-S) via the internal iliac artery or jugular vein. The doses were equitoxic. Platinum tissue concentration in uterus and platinum serum levels were measured after internal iliac arterial or intravenous (i.v.) infusion with these platinum compounds., Results: Platinum uterine concentration after intra-arterial infusion was significantly higher than that after i.v. infusion for each drug (P < .05). The ratios of platinum uterine concentration after intra-arterial infusion to those after i.v. infusion were 2.24 for cisplatin, 1.83 for carboplatin, and 1.67 for 254-S measured 20 minutes after drug administration. The area under the curve of filtrated platinum (micrograms/mL.hours) was significantly lower for cisplatin compared with carboplatin and 254-S in both infusion methods (1.5 for cisplatin, 32.1 for carboplatin, and 16.0 for 254-S after i.v. administration, and 0.8, 30.9, and 15.2 after intra-arterial administration, respectively)., Conclusion: Cisplatin produced the highest ratio of uterine to serum concentration of platinum after intra-arterial infusion.

The role of lymphadenectomy in patients with advanced ovarian cancer is controversial. To evaluate the effect of lymphadenectomy, we retrospectively assessed the outcome of 53 patients with stage III epithelial ovarian cancer who were divided into two groups, which were matched for age distribution and postoperative chemotherapy, but received different surgical procedures. A total of 29 patients (group A) underwent hysterectomy, bilateral salpingoophorectomy, omentectomy, and retroperitoneal lymphadenectomy, including resection of the para-aortic nodes. The remaining 24 patients (group B) received hysterectomy, bilateral salpingoophorectomy, and omentectomy without retroperitoneal lymphadenectomy. Postoperative chemotherapy consisted of a combination of cisplatin, Adriamycin, and cyclophosphamide in both groups. The 2-year survival rate for group A was significantly greater than that for group B, but there was no significant difference between the groups with regard to the estimated 5-year survival rate. The 2-year survival rate of patients with positive nodes who underwent lymphadenectomy was similar to that of patients with negative nodes. Multivariate analysis indicated that lymph node involvement did not relate to prognosis of the patients undergoing lymphadenectomy. While a defined randomized trial is required to reach substantive conclusion, it is suggested that lymphadenectomy may be useful for improvement of the prognosis of patients with advanced ovarian cancer.

Objective: To evaluate the use of transvaginal ultrasonography for diagnosing invasion of the bladder by cervical cancer., Methods: Twenty-one women with stages Ib-IIIb cervical cancer underwent radical hysterectomy or staging laparotomy. All had computed tomography (CT) scans and cystoscopic examinations, and five also underwent magnetic resonance imaging (MRI). During transvaginal ultrasonography, a transvaginal transducer was inserted into the anterior fornix of the vagina and the bladder wall was studied in the sagittal plane. The moveability of the bladder wall was assessed by the ability of the bladder to slide along the uterine cervix when the probe was pushed up against the bladder from the anterior fornix. Moveability was considered to indicate an intact bladder wall., Results: The accuracy of transvaginal ultrasonography was superior to that of the other methods for detecting bladder-wall invasion by cervical cancer. The accuracy was 95% for transvaginal ultrasonography, 76% for CT, 86% for cystoscopy, and 80% for MRI., Conclusion: Transvaginal ultrasonographic examination is useful for detecting invasion of the bladder wall by cervical cancer.

Objective: To determine whether cell kinetics in cervical cancer differ by patient age., Methods: We analyzed specimens from 118 women who had been treated for cervical squamous cell carcinoma. In a preliminary study, labeling indices were determined in 16 patients using bromodeoxyuridine in vitro. Adjacent portions of the same specimens were analyzed by flow cytometry. Proliferation indices were calculated and compared with labeling indices for 12 diploid tumors. For the remaining 102 tumors, paraffin-embedded specimens were analyzed by flow cytometry to determine DNA ploidy and proliferation index. Using these findings, we examined the relationship between tumor cell kinetics and age., Results: There was a significant correlation between the labeling index and age (r = 0.86, P < .001) and a weak but statistically significant correlation between the proliferation index and the labeling index (r = 0.58, P < .05). The proportion of aneuploid tumors increased with age. The cutoff point of highest statistical significance was 65 years (P = .025). The proliferation index showed an age-dependent shift, and the cutoff point of highest statistical significance was also 65 years. Aneuploid tumors were more common in elderly patients aged 65 or more years. Proliferation indices were also significantly larger in the elderly patients (P < .005). Although stage III tumors were more common in the elderly, stage was not related to ploidy pattern or to proliferation index., Conclusion: Tumor cell kinetics of cervical squamous cell carcinomas differ between elderly and younger women.

Intra-arterial infusion with cisplatin (CDDP) and bleomycin (BLM) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone. Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM. Two to four courses of the infusion therapy were given to each patient, and the response rate, the tumor and serum drug concentrations, and the cell kinetics in tumor tissue were evaluated. The response rate (CR+PR) was 71.4% according to the WHO criteria. There was no difference, in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders. Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment, both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors. These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy.

Cardiac anatomy and rhythm were evaluated in a fetus at 39 weeks' gestation in a pregnant woman referred because of severe fetal bradycardia with a persistent fetal heart rate of 50-60 beats per minute. M-mode echocardiograms revealed supraventricular bradyarrhythmia. Umbilical cord blood analysis did not, however, reveal fetal hypoxia. Diagnostic methods of fetal bradyarrhythmia are discussed, and the importance of differentiating bradyarrhythmia from bradycardia due to fetal hypoxia is emphasized.