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Biomedical subjects

E Tanaka

Publications and source records attributed to E Tanaka.

At least 145 records · Page 8Linked to original sources

Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors.

PURPOSE: To investigate the viability of perioperative fractionated HDR brachytherapy for malignant bone and soft tissue tumors, analyzing the influence of surgical margin. METHODS AND MATERIALS: From July 1992 through May 1996, 16 lesions of 14 patients with malignant bone and soft tissue tumors (3 liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1 leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at the Osaka University Hospital. The patients' ages ranged from 14 to 72 years (median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs in 5, the neck in 4, and a lower limb in 1. The resection margins were classified as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative fractionated HDR brachytherapy was started on the 4th-13th day after surgery (median: 6th day). The total dose was 40-50 Gy/7-10 fr/4-7 day (bid) at 5 or 10 mm from the source. Follow-up periods were between 19 and 46 months (median: 30 months). RESULTS: Local control rates were 75% at 1 year and 48% in 2 years, and ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8 uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive) resection margins, and all the 8 controlled lesions (100%) had marginal (microscopically positive) or wide (negative) margins. Of the total, 3 patients died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7 showed no evidence of disease. Peripheral nerve palsy was seen in one case after this procedure, but no infection or delayed wound healing caused by tubing or irradiation has occurred. CONCLUSION: Perioperative fractionated HDR brachytherapy is safe, well tolerated, and applicable to marginal or wide surgical margin cases.

Adolescent↗

Detection of GB virus-C/hepatitis G virus genome in peripheral blood mononuclear cells and liver tissue.

The replication site for the GB virus-C/hepatitis G virus (GBV-C/HGV) was investigated by using polymerase chain reaction (PCR)-based assays and in situ hybridisation. A total of 28 patients with consecutive GBV-C/HGV infection were enrolled in this study: Nine patients were being treated with immunosuppressive therapy after liver transplantation, and the remaining 19 patients were not receiving such treatment. GBV-C/HGV RNA was detected by using reverse transcriptase-polymerase chain reaction (RT-PCR) and was quantitated by using competitive RT-PCR in all patients. Positive and negative strands of GBV-C/HGV RNA in liver tissue were detected with in situ hybridisation by using RNA probes that were specific for the GBV-C/HGV genome. Concentrations of GBV-C/HGV RNA in serum were significantly higher (P=0.003) in the nine patients who were receiving immunosuppression (median, 10(7) copy/ml; range, 10(5)-10(7)) than in the 19 patients who were not receiving immunosuppressive therapy (median, 10(4) copy/ml; range, 10(2)-10(7)). In situ hybridisation of GBV-C/ HGV RNA was performed on paraffin-embedded liver tissue that was obtained from six patients with GBV-C/HGV infection. Two of those six patients were receiving immunosuppressive therapy, and four were not. Significant positive signals were observed in the samples from two of the six patients who were infected with GBV-C/HGV, but such signals were not observed in any of the six patients who were without the infection. The two patients with positive signals (both were undergoing immunosuppressive therapy) showed both positive and negative strands of GBV-C/HGV RNA in mononuclear cells that infiltrated into portal areas, but neither of the strands was observed in hepatocytes. Moreover, the GBV-C/HGV replication was analysed in peripheral blood mononuclear cells by using strand-specific PCR (conventional RT-PCR and rTth method). Two of the six patients were positive for negative-strand GBV-C/HGV RNA by using conventional RT-PCR. In conclusion, GBV-C/HGV replication was active under an immunosuppressive state, and it is suggested that GBV-C/HGV replicates in mononuclear cells.

Adolescent↗

Concurrent chemotherapy (5-fluorouracil and cisplatin) and radiation therapy followed by surgery for T4 squamous cell carcinoma of the esophagus.

BACKGROUND AND OBJECTIVES: Since the prognosis of patients with T4 squamous cell carcinoma (SCC) of the esophagus is extremely poor, an effective multimodal treatment needs to be established. METHODS: Forty-five patients with SCC of the esophagus at the T4 classification of the disease but no hematogenous metastasis were treated with concurrent chemoradiation therapy followed by surgical resection. Twenty-eight patients were treated with a regimen (protocol A) of 5-fluorouracil 750 mg/m2 on days 1-5 and 22-26, and cisplatin 70 mg/m2 on days 1 and 22. The remaining 17 patients were treated with a modified regimen (protocol B) of 5-fluorouracil 400 mg/m2 and cisplatin 10 mg/m2 on days 1-5, 8-12, 15-19, and 22-26. Radiation was delivered daily for 5 days/week for 4 weeks at the rate of 2 Gy/day to a total dose of 40 Gy in both protocols. RESULTS: A major clinical response was observed in 29 [3 complete response (CR) and 26 partial response (PR)] patients (64.4%). Twenty-eight patients (62.2%) underwent esophagectomy with no postoperative death. The median survival time of the resected patients (959 days) was significantly longer than that of the non-resected patients (178 days). Protocol B showed significantly higher pathologic effectiveness than protocol A. The pathologic CR rate for the main tumors was 1 (6.3%) of 16 patients for protocol A and 7 (58.3%) of 12 patients for protocol B. The pathologic CR rate for metastasized lymph nodes was 4/11 (36.4%) for protocol A and 5/5 (100%) for protocol B. Good histological response of the main tumors correlated well with long survival. The treatments were well tolerated except for one treatment-related death. CONCLUSIONS: Concurrent chemoradiation therapy followed by surgery is an effective and safe multimodal therapy for patients with primary inoperable T4 SCC of the esophagus.

Aged↗

Transfusion-associated TT virus infection and its relationship to liver disease.

TT virus (TTV) has been proposed as the causative agent of non-A to E hepatitis. We studied the association between TTV viremia and biochemical evidence of hepatitis in blood donors and prospectively-followed patients. TTV was found in 7.5% of 402 donors and in 11.0% of 347 patients before transfusion. The rate of new TTV infections was 4.7% in 127 nontransfused, and 26.4% in 182 transfused patients (P <.0001). The risk of infection increased with the number of units transfused (P <.0001). The rate of new TTV infections in 13 patients with non-A to E hepatitis (23.2%) was almost identical to the rate in 124 patients who were transfused, but did not develop hepatitis (21.8%). Of 45 patients with acute hepatitis C, 40.0% were simultaneously infected with TTV. TTV did not worsen the biochemical severity (mean ALT: 537 in TTV+; 550 in TTV-) or persistence of hepatitis C. In non-A to E cases, the mean ALT was 182 in those TTV-positive and 302 in TTV-negatives. No consistent relationship between alanine transaminase level and TTV DNA level was observed in 4 patients with long-term, sequential samples. Of 21 viremic subjects, 67% cleared TTV within 5 years (38% in 1 year); 33% were viremic throughout follow-up extending to 22 years. We conclude that TTV is a very common, often persistent infection that is transmitted by transfusion and by undefined nosocomial routes. We found no association between TTV and non-A to E hepatitis and no effect of TTV on the severity or duration of coexistent hepatitis C. TTV may not be a primary hepatitis virus.

Blood Donors↗

Nonfunctioning islet cell carcinoma of the pancreas: an evaluation of seven patients who underwent resection followed by long-term survival.

Islet cell carcinoma of the pancreas is a rare, indolent malignancy associated with a higher resectability rate and better survival than ductal carcinoma. This retrospective study presents the results of surgical treatment for nonfunctioning islet cell carcinoma of the pancreas in seven patients diagnosed and treated at Kurume University Hospital. There were two men and five women, with an average age of 54 years. Of the five tumors, four were located in the head of the pancreas, and the other three tumors were located in the body or tail of the pancreas. Epigastric pain was frequently the primary clinical symptom. By the time of diagnosis, four of the patients had regional disease, one of whom had lymph node and liver metastases, and one, liver metastases. Another patients was found to have lymph node metastases intraoperatively. Only one of the patients died of recurrent cancer, 21 years after the original operation. All of the patients who had liver metastases at the time of initial surgical treatment are now living at home. Thus, we conclude that nonfunctioning islet cell carcinomas are slow-growing tumors with a good prognosis if the main tumors and metastatic lesions are removed.

Adult↗

Nesidioblastosis with hyperinsulinemic hypoglycemia in adults: report of two cases.

We report herein the cases of two women, aged 34 years and 39 years, respectively, found to have hyperinsulinemic hypoglycemia after presenting with a history of episodes of temporary loss of consciousness, nausea, and fainting. Under the suspected diagnosis of insulinoma, localization procedures were carried out, but no tumor was found. In both patients, a definite gradient in insulin concentration was found in the pancreas by percutaneous transhepatic or intraoperative portal venous sampling, and a misdiagnosis of insulinoma of the pancreatic body was made. During exploratory laparotomy no tumor was palpable in the pancreas, and intraoperative ultrasonography showed no low echoic mass in the pancreas. A distal pancreatectomy was performed in both patients, and histopathological examination of the resected specimens revealed graded slight hyperplasia of the islet cells.

Adult↗

Transmission of and liver injury by TT virus in patients on maintenance hemodialysis.

To study the prevalence and clinical significance of TT virus (TTV) infection in hemodialysis patients, we tested for TTV DNA in serum, using the nested polymerase chain reaction. The prevalence of TTV DNA in 352 hemodialysis patients was 32%, significantly higher than that in 50 healthy blood donors (12%). The prevalence increased with age (P = 0.0098): it was 20% (22/110) in patients aged less than 49 years, 37% (69/188) in those aged 50-69 years, and 41% (22/ 54) in those aged over 70 years. Other clinical features and the prevalence of other hepatitis viral markers tested did not differ between patients with TTV DNA and those without it. The detection rate of hepatitis C virus (HCV) and hepatitis G virus (HGV) viremias increased with duration of hemodialysis and with the number of blood transfusion units, but the prevalence of TTV viremia did not. Twenty-nine of 91 patients followed for 5 years were initially positive for TTV DNA. Of these 29 patients, 17 (59%) carried this viremia for at least 5 years. Fourteen of the 62 patients (23%) who were initially negative for TTV DNA acquired TTV viremia. Serum alanine aminotransferase (ALT) levels were elevated in patients with HCV viremia but not in patients with HGV or TTV viremia. However, the mean ALT level in patients with all three viremias (HCV, HGV, and TTV) was significantly higher than that in patients with one or two of the viremias. More than 30% of the hemodialysis patients had TTV viremia and the carrier state was maintained for years. The hemodialysis procedures, including blood transfusion, did not seem to be crucial for the transmission of TTV. The pathogenic effects of TTV on hepatitis appear to be limited.

Adolescent↗

Gastric enterochromaffin-like-cell tumor with liver and splenic metastases.

We report a patient with gastric enterochromaffin-like-cell tumor with liver and splenic metastases. He was 68 years old and presented with major complaints of epigastric pain and weight loss. Under the diagnosis of gastric carcinoma with liver metastasis, total gastrectomy with splenectomy and lateral segmentectomy of the liver was performed. Intraoperative findings resulted in a diagnosis of adenocarcinoma T3N2P0H1, in stage IVa. Histological examination of the resected specimens showed a well differentiated neuroendocrine carcinoma (enterochromaffin-like-cell tumor) with liver and splenic metastasis which demonstrated high-grade lymphatic and vascular invasion. There was no lymph node metastasis. The tumor cells in the stomach, liver and spleen were immunoreactive for chromogranin A and Grimelius--positive. We review the literature, as well as presenting this case report.

Aged↗

Viscoelastic properties of canine temporomandibular joint disc in compressive load-relaxation.

The present study was designed to investigate the mechanical properties and load-relaxation of these discs in compression. Eight discs were used for the experiments. Compression was applied to specimens up to the specified strain, and a series of load-relaxation tests was conducted on each specimen from 0.25% strain to 2.0% strain with 0.25% intervals. The load-relaxation was monitored over a period of 2 min. The elastic moduli of the canine articular discs were 30.9 and 15.8 MPa at t = 0 and 120 sec, respectively, and the discs exhibited near-linear elastic characteristics at each time within a 2-min period. At all strains, the time-dependent load-relaxation curves showed that the load decreased markedly for the initial 30 sec, after which it levelled off after 120 sec with a steady nonzero level. This relaxation feature can be well represented by Kelvin's model. It is concluded that the canine temporomandibular joint disc can be represented as a linear viscoelastic material, and that it plays an important part as a stress absorber under compression.

Animals↗

T cell repertoire in the liver of patients with autoimmune hepatitis.

Despite a large number of T cells infiltrating into the liver of patients with autoimmune hepatitis (AIH), little is known about their roles or target antigens. To investigate the roles of these T cells in the pathogenesis of AIH, we have studied the clonality of alphabeta T cell populations in liver tissue by size spectratyping the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) Vbeta-chain transcripts. Analysis of nine AIH patients who had the HLA DR4 haplotype showed clonal expansion in all samples. More than two T cell clones expanded in most patients. Although the expression of the TCR Vbeta genes was different among the nine patients, clonal expansion of T cells expressing either TCR Vbeta2, 3, 4, 16, or 22 was observed in two patients or more. TCR Vbeta4 clones expanded in 5 cases. Cloning and sequencing of TCR Vbeta CDR3 from PCR products revealed no whole CDR3-shared clones among different patients. In conclusion, several T cell clonotypes first recognize target antigens, then expand and accumulate in the liver of AIH patients. These suggest heterogeneity of autoantigens and the complexity of AIH immunopathogenesis in individual patients.

Adult↗

Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system.

Psychotherapeutic drugs (antipsychotics and antidepressants) are widely used for treating anxiety. Many psychotherapeutic drugs are metabolized mainly by cytochrome P450 (CYP)2C19 and CYP2D6, and are often administered with other drugs. Therefore, it is necessary to be careful when co-administering psychotherapeutic drugs whose metabolism might be inhibited by other drugs. In particular, selective serotonin reuptake inhibitors (SSRIs) inhibit the metabolism of psychotherapeutic drugs mediated by CYP2C19 and CYP2D6. It is useful to phenotype CYP2C19 and CYP2D6 (extensive metabolizers or poor metabolizers) before giving such medication. Knowledge of substrates, inhibitors and inducers of CYP isoenzymes may help clinicians to anticipate and avoid psychotherapeutic drug interactions and improve rational prescribing practices. In addition, genotyping for these drugs may be also useful in preventing side-effects.

Antidepressive Agents↗

Clinically significant pharmacokinetic drug interactions between antiepileptic drugs.

Pharmacokinetic interactions between antiepileptics represent a major potential complication of epilepsy treatment because drug combinations are common. This review discusses pharmacokinetic drug interactions of clinical significance involving antiepileptics and cytochrome P450 (CYP). Most commonly used antiepileptics are eliminated through hepatic metabolism, catalysed by the enzymes CYP2C9, CYP2C19 and CYP3A4 and uridine diphosphate glucuronosyltransferase (UDGPT). Antiepileptics are associated with a wide range of drug interactions, including hepatic enzyme induction and inhibition. Phenytoin, phenobarbiral, primidone and carbamazepine induce CYP and UDPGT enzymes while valproic acid inhibits them. Avoidance of unnecessary polypharmacy, selection of alternative agents with lower interaction potential and careful dosage adjustments based on serum drug concentration monitoring and clinical observation are the main methods for reducing the risks associated with these interactions.

Anticonvulsants↗

Update: genetic polymorphism of drug metabolizing enzymes in humans.

The cytochrome P450 (P450 or CYP) monooxygenases, CYP2D6, CYP2C19, CYP2E1 and CYP2C9, and non-P450 monooxygenases, N-acetyltransferase, thioprine methyltransferases and dihydropyrimidine dehydrogenase, all display polymorphism. CYP2D6 and CYP2C19 have been studied extensively and, despite their low abundance in the liver, they have been found to catalyse the metabolism of many drugs. CYP2D6 has many allelic variants, whereas CYP2C19 has only two. Most variants are translated into inactive, truncated proteins or fail to express protein. There is, as yet, no clear information about CYP2E1 polymorphism. In addition, genetic differences in certain foreign-compound metabolizing enzymes, such as Phase II enzymes, have been shown to be associated with an increased risk of developing environmentally and occupationally related diseases such as cancer. When two drugs that are substrates of a polymorphic CYP enzyme are administered concomitantly during drug therapy, each will compete for that enzyme and competitively inhibit the metabolism of the other substrate. This can result in toxicity. Patients who are poor metabolizers (PMs), extensive metabolizers (EMs) and ultrarapid metabolizers (URMs) can be identified. Having such information will help in determining the appropriate dosage of certain drugs when treating patients with an inherited abnormality of a drug-metabolizing enzyme. In view of the remarkable progress in this particular field, it is to be expected that more genetic polymorphisms will be discovered in the near future.

Cytochrome P-450 Enzyme System↗

Gender-related differences in pharmacokinetics and their clinical significance.

In this review I have attempted to summarize gender differences in pharmacokinetics involving the cytochrome P450 (CYP) isozymes of young and mature adults, excluding the effects of the menstrual cycle, use of oral contraceptives and pregnancy. Sex differences in drug metabolism and elimination are mainly related to steroid hormone levels. CYP3A4, responsible for the metabolism of over 50% of therapeutic drugs, exhibits higher activity in women than in men. Nonetheless, the absence of a sex difference has been reported by some workers. The activity of several other CYP (CYP2C19, CYP2D6, CYP2E1) isozymes and the conjugation (glucuronidation) activity involved in drug metabolism may be higher in men than in women. Drug metabolism in women is affected by sex-specific factors (menopause, pregnancy and menstruation) in addition to the cigarette smoking, drug ingestion and alcohol consumption that are more commonly observed factors in men. Furthermore, they are affected by physiological factors such as drug absorption, protein binding and elimination. Thus, careful attention should be paid to the side-effects and toxicity arising from sex differences in drug metabolism in clinical situations. Although there are specific ethical considerations regarding carrying out drug trials in women, the relationship between the side-effects and toxicity that may be influenced by hormones during drug metabolism and drug treatment needs further study.

Cytochrome P-450 Enzyme System↗

Clinically significant pharmacokinetic drug interactions with benzodiazepines.

The reports of interactions between benzodiazepines (BZPs) and other drugs (e.g., antidepressants, selective serotonin reuptake inhibitors, antiulcer drugs, antiepileptic drugs, macrolide antibiotics) during their combined use are reviewed. In general, metabolism of BZPs is delayed when combined with a number of other drugs but some reports have suggested otherwise. In recent years, the cytochrome P450 (P450 or CYP) isoenzyme that catalyses the metabolism of BZPs has also been identified. BZPs are mainly catalysed by CYP3A4. When published reports are studied, it appears necessary to be exceptionally careful about interactions mainly between BZPs and selective serotonin reuptake inhibitors, cimetidine, antiepileptic drugs, macrolide antibiotics and antimycotics. More information is necessary to identify individuals at greatest risk of drug interactions and adverse events.

Animals↗

Reliability of childhood mental disorder: diagnoses by Japanese psychologists.

The recent entry of psychologists into psychiatric practices and schools in Japan calls for diagnostic skills, because psychiatrists are less available in such settings. We examined the reliability of the diagnoses of 10 DSM-IV childhood mental disorders by 11 Japanese psychologists, using 20 case vignettes. Most categories had good reliability (kappa), except for attention deficit hyperactivity disorder. Japanese clinical psychologists may be able to use DSM-IV reliably as a tool for diagnosis of childhood psychiatric disorders, if sufficient training is provided.

Adolescent↗

Precedents of perceived social support: personality and early life experiences.

In order to examine the effects of personality and early life experiences on perceived social support, a total of 97 young Japanese women were investigated. Current interpersonal relationships were measured by an interview modified from Henderson et al.'s Interview Schedule for Social Interaction (ISSI). Personality was measured by Cloninger et al.'s Temperament and Character Inventory. Early life experiences at home and outside of home were also identified in the interview. The number of sources of perceived support was correlated with self-directness, while satisfaction with perceived support was correlated with novelty seeking and with low harm avoidance. No early life experiences--early loss of a parent, perceived parenting, childhood abuse experiences, experiences of being bullied and/or other life events--showed significant correlations with the number or satisfaction of supportive people. The quantity and quality of perception of social support differ in their link to personality, and perceived social support may, to some extent, be explainable in terms of personality.

Adult↗