Biomedical subjects

Toshikazu Ito

Publications and source records attributed to Toshikazu Ito.

13 recordsLinked to original sources

PubMed2006

Test of association between haplotypes and phenotypes in case-control studies: examination of validity of the application of an algorithm for samples from cohort or clinical trials to case-control samples using simulated and real data.

The use of haplotype information in case-control studies is an area of focus for the research on the association between phenotypes and genetic polymorphisms. We examined the validity of the application of the likelihood-based algorithm, which was originally developed to analyze the data from cohort studies or clinical trials, to the data from case-control studies. This algorithm was implemented in a computer program called PENHAPLO. In this program, haplotype frequencies and penetrances are estimated using the expectation-maximization algorithm, and the haplotype-phenotype association is tested using the generalized likelihood ratio. We show that this algorithm was useful not only for cohort studies but also for case-control studies. Simulations under the null hypothesis (no association between haplotypes and phenotypes) have shown that the type I error rates were accurately estimated. The simulations under alternative hypotheses showed that PENHAPLO is a robust method for the analysis of the data from case-control studies even when the haplotypes were not in HWE, although real penetrances cannot be estimated. The power of PENHAPLO was higher than that of other methods using the likelihood-ratio test for the comparison of haplotype frequencies. Results of the analysis of real data indicated that a significant association between haplotypes in the SAA1 gene and AA-amyloidosis phenotype was observed in patients with rheumatoid arthritis, thereby suggesting the validity of the application of PENHAPLO for case-control data.

Algorithms↗

PubMed2006

[A case of postoperative liver metastasis from bile duct carcinoma responding to transarterial chemoembolization].

A 77-year-old man underwent pylorus-preserving pancreatoduodenectomy for bile duct carcinoma in October 2000. Histological diagnosis was moderately-differentiated tubular adenocarcinoma, pT 2 (ss, pHinf 0, pPanc 1, pPV 0, pA 0), pN 0, and final Stage II. The patient was periodically observed after operation. In September 2003, follow-up abdominal CT examinations revealed a liver tumor, 89 x 62 x 60 mm in size, at the anterior segment. Transarterial chemoembolization with 5-FU, epirubicin, mitomycin C and superabsorbent polymer microsphere was initiated under the diagnosis of liver metastasis. After completion of 4 chemoembolizations, the tumor responded partially and diminished to 50 x 16 x 14 mm in CT and superparamagnetic iron oxide-enhanced MRI. Currently, the patient is free from any signs of relapse.

Adenocarcinoma↗

PubMed2006

[Efficacy of uracil/tegafur (UFT) plus oral Leucovorin (LV) therapy for colorectal cancer in elderly patients].

BACKGROUND & AIMS: The uracil/tegafur (UFT) plus oral Leucovorin (LV) regimen is one of the standard chemotherapy modalities for colorectal cancer, and has been reported to have fewer side effects. In this study, we investigated the efficacy and toxicity of UFT/LV regimen in elderly patients. PATIENTS AND METHODS: The subjects were twelve patients older than 70 years (median age, 76 years), who received a UFT/LV regimen for colorectal cancer between January 2004 and June 2005. Chemotherapy was attempted for metastatic colorectal cancer in seven patients and for postoperative adjuvant chemotherapy in five patients. The response rate and toxicity were compared with those of patients younger than 70 years old. RESULTS: Four courses of chemotherapy, in median, were delivered. The regimen consisting of UFT 300 mg/m(2) was completed in all patients. One patient achieved a complete response and another patient a partial response, thus resulting in an overall response rate of 28.6%. Three patients experienced Grade 1 diarrhea, and seven patients had Grade 1 or 2 anemia. Grade 3 or 4 toxicity was not recognized in all patients. CONCLUSIONS: Treatment with UFT/LV regimen is effective and well tolerated in elderly as well as younger patients.

Adult↗

PubMed2005

A novel back school using a multidisciplinary team approach featuring quantitative functional evaluation and therapeutic exercises for patients with chronic low back pain: the Japanese experience in the general setting.

STUDY DESIGN: A prospective cohort study. OBJECTIVES: To introduce a novel back school for the treatment of patients with chronic low back pain (CLBP), and to report its clinical results. SUMMARY OF BACKGROUND DATA: Although back school is one of the treatment methods for patients with CLBP, its efficacy and appropriate style remain controversial. No studies have been published regarding the combined program of back school with a multidisciplinary team approach. METHODS: A total of 182 patients with CLBP (74 men and 108 women; average age, 43.8 years) participated in this study. All patients were enrolled in the back school using a multidisciplinary team approach featuring quantitative functional evaluation and therapeutic exercises. The following outcome measures were evaluated at the baseline, and 6 and 12 months after the enrollment: the level of pain evaluated with a Visual Analog Scale (VAS), flexibility of trunk and hamstrings (finger-floor distance, straight leg raising), trunk muscle strength and endurance, frequency of therapeutic exercises, and self-reported patient satisfaction. RESULTS: An averaged VAS score was 6.2 before enrollment in the program and 2.8 at follow-up. The pain improved in 141 patients (80.8%), did not change in 27 (15.4%), and was aggravated in 7 (3.8%). There was statistically significant improvement of finger-floor distance, trunk muscle strength, and endurance in the patients whose pain was relieved after enrollment in the program (P < 0.05). The compliance with the exercise program was significantly correlated with the clinical results (P < 0.05). CONCLUSIONS: We developed a novel back school using a multidisciplinary team approach, featuring quantitative functional evaluation and therapeutic exercises. The current study demonstrated that our program could provide a satisfactory result for the treatment of patients with CLBP. The quantitative functional evaluation was a worthwhile outcome measure when evaluating the efficacy of the treatment program. Teaching body mechanics and performing the therapeutic exercises through the multidisciplinary team approach are essential to managing CLBP in a general setting.

Adult↗

PubMed2005

[Peritoneal dissemination from gastrointestinal stromal tumor of small intestine responding completely to imatinib mesylate (STI 571)].

The prognosis of metastatic or recurrent GISTs is poor, because these tumors resist chemotherapy and radiotherapy. We report a patient with recurrent GIST who underwent molecularly targeted therapy with imatinib, a novel oral tyrosine kinase inhibitor. A 64-year-old man presented with large intra-abdominal mass. The patient had a history of jejunostomy with colostomy for intestinal GIST. The abdominal mass was phi3 x 3.5 cm in size with ascites at Douglas, as determined by computed tomography, and was diagnosed as a peritoneal relapse of GIST. Treatment with imatinib daily was started. After 1 month of treatment with imatinib, reduction of the abdominal tumor began to be recognized on palpation. Computed tomographic scanning at 11 months revealed that the tumor had completely disappeared. The major side effect was drug eruption,which was easily manageable with 2 weeks drug holidays. Imatinib shows promise as a safe and effective drug for the treatment of patients with recurrent GISTs.

Antineoplastic Agents↗

PubMed2005

[A case of recurrent colon cancer responding completely to uracil/tegafur (UFT) plus oral leucovorin (LV) therapy].

The patient was a 78-year-old woman who underwent right hemicolectomy with lymph node dissection (D 2) for cecal cancer in June 2003. Histological diagnosis was moderately differentiated adenocarcinoma, ss, n(-), P 0, H 0, M (-), stage II. Adjuvant chemotherapy was not conducted, and the patient was periodically observed after operation. In April 2004, the serum CEA level was elevated to 14.9 ng/ml. Abdominal CT examinations revealed a tumor, 50 x 35 x 50 mm in size, on the right iliopsoas muscle close to the anastomotic site. Systemic chemotherapy with UFT + Leucovorin was initiated under the diagnosis of local recurrence. Only grade 1 body weight loss,pigmentation, pruritus, and anorexia were recognized during chemotherapy. However, these complications did not require administration. After completion of 6 courses of this chemotherapeutic regimen,the serum CEA level was normalized at 3.1 ng/ml, and CT scan revealed the tumor had disappeared in November 2004. Currently, the patient is free from any signs of recurrence and has maintained a complete remission (CR).

Adenocarcinoma↗

PubMed2004

Anatomic evaluation of postural bronchial drainage of the lung with special reference to patients with tracheal intubation: which combination of postures provides the best simplification?

BACKGROUND: Although several sequences of specific postures, each corresponding to a particular lung segment, have been recommended for therapeutic bronchial drainage, these are based on little or no anatomic evidence. Moreover, because these sequences are too complex, especially for intubated patients, they require simplification. MATERIALS AND METHODS: The courses of the segmental bronchi B(1), B(2), B(1 + 2), B(3), and B(6) and their subsegmental bronchi are extremely variable. This can result in a small branching angle at the subsegmental bronchial origin. Using 106 lungs, we measured the branching angles of the subsegmental bronchi and examined their running directions in each posture of the sequences recommended for bronchial drainage. RESULTS: A small branching angle (< 120 degrees ) at the subsegmental bronchial origin was sometimes evident, and this made postural drainage difficult. Drainage of B(3) and B(6) was often difficult because they formed angles of < 45 degrees from the horizontal in certain postures (supine for B(3) and prone for B(6)). Further, we found a 45 degrees rotative prone position effective for draining B(1)a and B(6). CONCLUSION: Our anatomic findings predicted increased effectiveness in a sequence of postures: supine, 45 degrees rotative prone with left side up, 45 degrees rotative prone with right side up, and return to supine for simple, safe, and effective bronchial drainage, especially for patients with tracheal intubation. The 10 degrees right-side-up supine and 45 degrees rotative prone with head raised 45 degrees positions seemed helpful if added to the basic sequence.

Bronchi↗

PubMed2004

Association test algorithm between a qualitative phenotype and a haplotype or haplotype set using simultaneous estimation of haplotype frequencies, diplotype configurations and diplotype-based penetrances.

Analysis of the association between haplotypes and phenotypes is becoming increasingly important. We have devised an expectation-maximization (EM)-based algorithm to test the association between a phenotype and a haplotype or a haplotype set and to estimate diplotype-based penetrance using individual genotype and phenotype data from cohort studies and clinical trials. The algorithm estimates, in addition to haplotype frequencies, penetrances for subjects with a given haplotype and those without it (dominant mode). Relative risk can thus also be estimated. In the dominant mode, the maximum likelihood under the assumption of no association between the phenotype and presence of the haplotype (L(0max)) and the maximum likelihood under the assumption of association (L(max)) were calculated. The statistic -2 log(L(0max)/L(max)) was used to test the association. The present algorithm along with the analyses in recessive and genotype modes was implemented in the computer program PENHAPLO. Results of analysis of simulated data indicated that the test had considerable power under certain conditions. Analyses of two real data sets from cohort studies, one concerning the MTHFR gene and the other the NAT2 gene, revealed significant associations between the presence of haplotypes and occurrence of side effects. Our algorithm may be especially useful for analyzing data concerning the association between genetic information and individual responses to drugs.

Algorithms↗

PubMed2004

Simultaneous estimation of haplotype frequencies and quantitative trait parameters: applications to the test of association between phenotype and diplotype configuration.

The analysis of the haplotype-phenotype relationship has become more and more important. We have developed an algorithm, using individual genotypes at linked loci as well as their quantitative phenotypes, to estimate the parameters of the distribution of the phenotypes for subjects with and without a particular haplotype by an expectation-maximization (EM) algorithm. We assumed that the phenotype for a diplotype configuration follows a normal distribution. The algorithm simultaneously calculates the maximum likelihood (L0max) under the null hypothesis (i.e., nonassociation between the haplotype and phenotype), and the maximum likelihood (Lmax) under the alternative hypothesis (i.e., association between the haplotype and phenotype). Then we tested the association between the haplotype and the phenotype using a test statistic, -2 log(L0max/Lmax). The above algorithm along with some extensions for different modes of inheritance was implemented as a computer program, QTLHAPLO. Simulation studies using single-nucleotide polymorphism (SNP) genotypes have clarified that the estimation was very accurate when the linkage disequilibrium between linked loci was rather high. Empirical power using the simulated data was high enough. We applied QTLHAPLO for the analysis of the real data of the genotypes at the calpain 10 gene obtained from diabetic and control subjects in various laboratories.

Algorithms↗

PubMed2004

[A case of advanced colon cancer responding completely to systemic 5-fluorouracil/l-leucovorin therapy].

A 79-year-old man was admitted for advanced transverse colon cancer with large bowel obstruction. Twelve years earlier he underwent a total gastrectomy with Roux-en Y reconstruction for gastric cancer. No metastasis was detected preoperatively. Exploratory laparotomy revealed massive direct invasion of the mesenterium of the jejunum for Roux-en Y reconstruction. The primary lesion was unresected and transverse colostomy was made. Systemic chemotherapy with 5-fluorouracil and l-leucovorin was scheduled for a total of 4 courses postoperatively. After completion of this chemotherapeutic regimen, a CT scan and colonofiberscopy revealed the primary lesions had disappeared, and a histological examination of biopsy confirmed that the patient had achieved a complete remission (CR). There was no severe side effect during chemotherapy. The patient is presently enjoying a good general condition and has been free from any sign of recurrence.

Adenocarcinoma↗

PubMed2003

Estimation of haplotype frequencies, linkage-disequilibrium measures, and combination of haplotype copies in each pool by use of pooled DNA data.

Inference of haplotypes is important for many genetic approaches, including the process of assigning a phenotype to a genetic region. Usually, the population frequencies of haplotypes, as well as the diplotype configuration of each subject, are estimated from a set of genotypes of the subjects in a sample from the population. We have developed an algorithm to infer haplotype frequencies and the combination of haplotype copies in each pool by using pooled DNA data. The input data are the genotypes in pooled DNA samples, each of which contains the quantitative genotype data from one to six subjects. The algorithm infers by the maximum-likelihood method both frequencies of the haplotypes in the population and the combination of haplotype copies in each pool by an expectation-maximization algorithm. The algorithm was implemented in the computer program LDPooled. We also used the bootstrap method to calculate the standard errors of the estimated haplotype frequencies. Using this program, we analyzed the published genotype data for the SAA (n=156), MTHFR (n=80), and NAT2 (n=116) genes, as well as the smoothelin gene (n=102). Our study has shown that the frequencies of major (frequency >0.1 in a population) haplotypes can be inferred rather accurately from the pooled DNA data by the maximum-likelihood method, although with some limitations. The estimated D and D' values had large variations except when the /D/ values were >0.1. The estimated linkage-disequilibrium measure rho2 for 36 linked loci of the smoothelin gene when one- and two-subject pool protocols were used suggested that the gross pattern of the distribution of the measure can be reproduced using the two-subject pool data.

Algorithms↗

PubMed2003

Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma.

BACKGROUND/PURPOSE: We retrospectively investigated the clinicopathologic features and outcome of 51 patients who underwent hepatectomy for intrahepatic cholangiocellular carcinoma (ICC) between 1991 and 2000, and we also analyzed the potential prognostic factors for long-term survival. METHODS: There were 27 men and 24 women, with a mean age of 63.7 years. The surgical procedures were extended right or left hepatectomy (15 cases), right or left hepatectomy (19 cases), bisegmentectomy (3 cases), segmentectomy (7 cases), and subsegmentectomy (7 cases). The macroscopic findings of the excised tumor showed the mass-forming (MF) type (31 cases), the periductal-infiltrating (PI) type (13 cases), and the intraductal growth (IG) type (7 cases). RESULTS: The patients with the MF type had a significantly higher incidence of lymph node metastasis (44.8%), as compared to those with the PI or IG type (15.0%). Two patients who died of hepatic failure during their hospital stay were excluded from this survival study. The cumulative 1-, 3-, and 5-year survival rates in 49 patients who underwent liver resection were 68.2%, 44.1%, and 32.4%, respectively. The patients with the IG type had the best outcome, followed by those with the PI type and MF type. The survival rates with or without lymph node metastasis were 9.0% and 60.6% at 3 years, and 9.0% and 42.9% at 5 years, respectively ( P << 0.05). The 1-, 2-, and 3-year survival rates in the MF-type patients with lymph node metastasis were 25.4%, 16.9%, and 0%, respectively. Eight patients (15.7%) survived for more than 5 years after operation. The gross appearance of these tumors was the PI type in 5 patients, the IG type in 2, and the IG + MF type in 1. Except for one case with the PI-type tumor, lymph node metastasis was not observed. All of the 5-year survivors underwent curative resection and none of them had any positive surgical margin. CONCLUSION: Analysis of the clinicopathologic factors influencing the survival after surgical treatment showed that the macroscopic type, surgical curability, lymph node metastasis, tumor size, and cancer-free margin were the most predictive.

Aged↗

PubMedDate not supplied

Evaluation of portal vascular resistance using an intraoperative Doppler ultrasound.

BACKGROUND/AIMS: To evaluate portal vascular resistance using Doppler ultrasound intraoperatively. METHODOLOGY: We measured maximum flow velocities and pressures of umbilical portion of the left portal branch before and after clamping of the right main branch of the Glisson's sheath. We proposed a new index, simplified portal resistive index, that was the ratio of the difference of the portal venous pressure to the difference of maximum portal flow velocity. RESULTS: There were good correlations between portal vascular resistance and simplified portal resistive index. Simplified portal resistive index was found to become higher as fibrotic changes progressed, and there were significant differences between normal liver, chronic hepatitis, and liver cirrhosis. CONCLUSIONS: Simplified portal resistive index evaluated using intraoperative Doppler ultrasound is an easy and reliable index for assessing portal vascular resistance during liver surgery.

Adult↗