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Biomedical subjects

M Fujimori

Publications and source records attributed to M Fujimori.

At least 55 records · Page 3Linked to original sources

Age at onset and language disturbances in Alzheimer's disease.

This study examined the effect of age at symptom onset of Alzheimer's disease (AD) on the pattern of language disturbance. We assessed 150 consecutive patients with a clinical diagnosis of mild-to-moderate AD using the Western Aphasia Battery and a 100-item picture-naming test. A multivariate linear regression analysis examined the effect of age at onset after controlling for gender, education, severity of dementia and duration of the disease. Patients with early onset performed significantly worse than did patients with late onset on the word comprehension and sequential commands subtests. On the other hand, late-onset patients performed more poorly than early-onset patients on the picture-naming test in a subgroup with mild language deficits. However, the trend disappeared in other subgroups with more degraded language function. We consider that the concomitant effects of normal aging worsened the picture-naming deficits in the late-onset patients, and the rapid decline of naming ability in the early-onset patients masked the aging effect with the progression of language deficits. The deterioration of word comprehension and the rapid decline of naming ability are the characteristics of early-onset patients. The different patterns of language deficits between early- and late-onset patients may correspond to the genetic heterogeneity of AD.

Age of Onset↗

Changes in thyroid function and immunological parameters long after subtotal thyroidectomy for Graves' disease.

OBJECTIVE: To find out whether subtotal thyroidectomy results in long term stable functional and immunological remission in patients with Graves' disease. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 176 patients who underwent subtotal thyroidectomy for Graves' disease, 1970-79. INTERVENTION: Follow up surveys in 1984 and 1992. MAIN OUTCOME MEASURES: Changes in thyroid function, antibody titres, and lymphocyte subsets. RESULTS: 29/79 patients (39%) who were euthyroid in 1984 had evidence of thyroid dysfunction in 1992. Of the 8 patients with latent hypothyroidism in 1984, 3 (38%) had become euthyroid by 1992, and none required treatment. Of the 29 patients who were hypothyroid in 1984, 5 had latent hypothyroidism and 1 was euthyroid in 1992, and of the 18 patients with recurrent hyperthyroidism in 1984, 1 had become euthyroid by 1992. The number of positive titres to TSH-binding inhibitory immunoglobulin was significantly higher in the recurrence group (31/36, 86%) compared with the hypothyroid (7/26, 27%), latent hypothyroidism (8/37, 22%), and euthyroid (22/77, 29%) groups (p < 0.01). There were also significant differences in the mean (SD) number of Leu HLA DR subsets between the control (17 (3), n = 18) and recurrence (21 (6), n = 38), hypothyroid (22 (6), n = 35), latent hypothyroidism (22 (6), n = 22), and euthyroid (22 (9), n = 64) groups (p < 0.002). There were no differences in the number of T cell subsets among the groups. CONCLUSION: Treatment of Graves' disease by subtotal thyroidectomy does not necessarily result in stable late functional or immunological remission. Long term follow up of such patients may be necessary.

Antigens, CD↗

Effectiveness of preoperative radioactive iodine (131I) therapy for locally advanced papillary thyroid cancer: a case report.

We report here the effectiveness of preoperative radioactive iodine-131 (131I) therapy for locally advanced thyroid cancer. A 57-year-old woman demonstrated a hard neck tumor that markedly invaded the surrounding organs. The cytological diagnosis of the tumor using fine-needle aspiration biopsy was papillary carcinoma. Because curative resection of the tumor appeared difficult at her first visit, 131I therapy was performed prior to surgery and was more useful than expected. After 3 131I treatments, the tumor size was greatly reduced, and the patient underwent a curative operation. Histopathological diagnosis was well differentiated papillary carcinoma, pT4 and pN1b. The postoperative clinical course was uneventful. There have been no definitive reports using 131I as preoperative treatment for inoperable thyroid cancer. We suggest that 131I therapy may also be beneficial as neoadjuvant therapy for locally advanced thyroid carcinoma.

Biopsy, Needle↗

The effects of intrinsic nitric oxide on cardiac neural regulation in cats.

UNLABELLED: In this study, we aimed to elucidate the effects of intrinsic nitric oxide (NO) on cardiac neural regulation. Twenty-two cats were anesthetized with 1.5% isoflurane and allocated to Group I (intact; n = 7), Group D (denervated baroreceptors and vagi; n = 8), or Group B (autonomic blockade with i.v. hexamethonium, propranolol, and atropine; n = 7). Cardiac sympathetic nerve activity (CSNA), mean arterial pressure (MAP), sinus heart rate (HR), and A-H and H-V intervals during pacing (150 bpm) were measured before and after i.v. administration of a NO synthase inhibitor, NG-nitro-L-arginine (L-NNA, 30 mg/kg) and after reversal with an excessive dose of L-arginine (300 mg/kg), before and during intermittent electrical stimulation of the posterior hypothalamus. L-NNA significantly increased MAP in Groups I and B, but not in Group D. L-NNA significantly decreased HR and lengthened A-H in Group I, but not in other groups. L-arginine further decreased HR and lengthened A-H unexpectedly. The reasons for these findings could not be determined in this study. L-NNA did not change CSNA. Hypothalamic stimulation did not potentiate L-NNA-induced changes in CSNA, hemodynamic variables, and atrioventricular conduction. In conclusion, intrinsic NO may modulate atrioventricular conduction and sinus rate through a vagal cholinergic, rather than a nonautonomic mechanism. IMPLICATIONS: Elucidating the roles of intrinsic nitric oxide (NO) on cardiac neural regulation is important. In intact, vagotomized, and baroreceptor-denervated or pharmacologically autonomic blockaded cats, an NO synthesis inhibitor was administered, and atrioventricular conduction and cardiac sympathetic neural discharge were measured. The results suggest a vagal cholinergic mechanism of intrinsic NO.

Anesthetics, Inhalation↗

Bromocriptine treatment for perseveration in demented patients.

Some forms of behavioral perseveration may reflect the disruption of specific neurotransmitter systems including mesencephalic dopaminergic projection. We present an open-labeled trial of a dopamine agonist for treating perseveration in dementia. Eight patients with ischemic vascular or degenerative dementia completed a 25-day trial of bromocriptine with a maximum daily dose of 10 mg. Patients were assessed with neuropsychological scales and a test battery for detecting perseveration. Recurrent and stuck-in-set types of perseveration significantly improved during the treatment, whereas measures for general attention and overall cognitive function showed no significant changes. We assume that bromocriptine supplemented the mesolimbocortical or ventral mesostriatal dopamine system ameliorated a certain frontal lobe function such as focused attention or working memory and improved the patients' perseverations. Although this study is preliminary because of the small sample size and open-labeled design, the results underline the possibility of pharmacotherapy for perseveration and recommend a double-blind, placebo-controlled study.

Aged↗

Age at onset and visuocognitive disturbances in Alzheimer disease.

We examined the relation of age at onset and visuocognitive disturbances in Alzheimer disease (AD) using a large sample of patients, quantitative neuropsychological measures, and multivariate statistics controlling for gender, education, stage of dementia, and disease duration. Significant positive coefficients were obtained with forward and backward digit and visual spans, visual counting, copying Rey complex figure, and block design task. The results indicated that patients with early-onset AD performed worse than late-onset AD patients on these tasks. There was no significant effect of age at onset on identification of overlapping figures, visual form discrimination, or Raven's colored progressive matrices. These findings confirm the greater attentional and visuospatial impairments in early onset patients when these confounding factors were controlled for, although no significant effect of age at onset in visuoperceptual function was observed.

Age Factors↗

Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 in thyroid diseases: difference between neoplasms and hyperplastic lesions.

We studied the expression of both fibroblast growth factor-2 (FGF-2) and FGF receptor-1 (FGFR-1) in various histological types of human thyroid neoplastic and hyperplastic tissues to clarify the biological behavior of FGF-2. A total of 37 malignant tumors (24 papillary carcinomas, 10 follicular carcinomas, 3 anaplastic carcinomas), 8 follicular adenomas, and 12 adenomatous goiters were examined by immunohistochemical methods. With immunohistochemical staining, both FGF-2 and FGFR-1 were frequently detected in human thyroid carcinoma (79.2 to 100% and 80 to 100%, respectively). In thyroid hyperplastic lesions such as adenomatous goiter, the FGF-2 immunoreactivity in follicular cells was detected in 2 of 12 adenomatous goiters (16.7%). In contrast, FGFR-1 immunoreactivity was detected in 66.7% of cases of this disease. The endothelial cells of microvessels in the stroma adjacent to the neoplasms and hyperplastic lesions also showed cytoplasmic FGF-2 immunoreactivity. The difference between FGF-2 and FGFR-1 expression in adenomatous goiters was statistically significant (P<0.05). Furthermore, the difference in FGF-2 immunoreactivity between carcinoma and adenomatous goiter was statistically significant (P=0.0001). The present investigation demonstrated the possibility of an autocrine mechanism of action of FGF-2 in human thyroid carcinoma. Moreover, in thyroid hyperplastic lesions, FGF-2 derived from the stroma might be involved in the formation of nodular and/or diffuse goiters.

Adenocarcinoma, Follicular↗

[Telomerase activity in benign proliferative breast disease and breast cancer].

The application of telomerase activity is expected to serve as a reliable indicator of biological malignancy in breast tumors. We performed a study to quantify telomerase activity, the results of which revealed that this activity tends to be unexpectedly low in scirrhous carcinoma having low histological differentiation. It is therefore felt that additional studies at the tissue level using in situ hybridization will be required in the future. Although we think that atypical cystic duct is a true pre-cancerous lesion in the sense of having a high possibility of progressing into breast cancer, it will be interesting to determine whether or not the tissue is composed of cells having telomerase activity.

Breast Diseases↗

Clinical significance of the increased multidrug resistance-associated protein (MRP) gene expression in patients with primary breast cancer.

The efficacy of cancer treatment is limited by either intrinsic or acquired resistance to various chemotherapeutic agents. To evaluate the clinically important factors related to prognosis in primary breast cancer retrospectively, we investigated the expression of the following genes involving acquirement of drug resistance: multidrug resistance 1 (MDRl), multidrug resistance-associated protein (MRP), and topoisomerase (Topo) I, II alpha, and II beta. Using an RT-PCR method, we semiquantified the gene expression level in untreated stage II breast cancer tissue (n = 27) and noncancerous breast tissue (n = 10). Among the 27 cancer patients, who were all treated by adjuvant chemoendocrine therapy after surgery, 10 patients showed relapse within the following 10 years whereas 17 patients did not. The gene expression levels of MDRl, MRP, and Topo I, II alpha, and II beta were normalized to the level of the beta 2-microglobulin RT-PCR product. MRP mRNA expression was detected in 70% of the breast cancer tissues and its expression levels were significantly increased in the cancer group compared with the noncancerous breast tissues. Furthermore, the MRP level was much higher in the relapsed patient group. On the other hand, there were no significant differences in the MDRl mRNA levels between the noncancerous and cancer groups. Although Topo II alpha mRNA was not detected in noncancerous breast tissues, it was detected in 52% of the breast cancer tissues. In cancer patients, no significant difference in Topo II alpha mRNA levels was observed between the relapsed and nonrelapsed groups. These findings suggest that MRP might be used as one of the markers for poor prognosis in patients with breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Genotyping of the CYP1A1 and GSTM1 genes in esophageal carcinoma patients with special reference to smoking.

BACKGROUND: Aromatic hydrocarbons, including benzol[a]pyrene, in tobacco smoke first require metabolic activation by phase I enzymes, cytochrome P450s (CYP450s), and then are subjected to detoxification by phase II enzymes, the glutathione-S-transferases. A high risk lung carcinoma group has been reported to have specific polymorphisms of the cytochrome P450 (CYP1A1) gene and the glutathione-S-transferase (GSTM1) gene. In this study, the authors investigated whether such genotypes were also risk factors for esophageal carcinoma. METHODS: Subjects were comprised of 89 esophageal carcinoma patients and 137 noncancer controls. Forty-nine of the patients and 60 of the control subjects were smokers. Genotypic studies of both CYP1A1 and GSTM1 were performed in the cancer tissues of all 89 patients. Genotypes of peripheral blood leukocytes taken from the control subjects were also determined. Genotypes of the CYP1A1 and GSTM1 genes were determined by the polymerase chain reaction. RESULTS: Patients who were heavy smokers with the genotypes Val/Val (V/V) for CYPIAI and the combined genotype of V/V for CYP1A1 and GSTM1- were a statistically high risk group compared with control subjects (P < 0.01, chi-square = 10.6 vs. P < 0.01, chi-square = 11.0). The association of V/V for CYPIAI with a smoking index > or = 600 in esophageal carcinoma patients was estimated at 6.63 (95% confidence interval [CI], 1.86-23.7). The association of combined genotypes of V/V of CYP1A1 and GSTM1 with a smoking index > or = 600 in esophageal carcinoma patients was estimated at 12.7 (95% CI, 1.97-81.8) CONCLUSIONS: Specific genotypes of the CYP1A1 and GSTM1- genes are related to the incidence of esophageal carcinoma, especially in heavy smokers.

Adult↗

Postoperative outcome of insufficient surgery for small differentiated thyroid carcinoma.

We performed conservative surgery for small differentiated thyroid carcinoma, but also inadvertently carried out minimal insufficient surgery, such as enucleation (Ex) or partial lobectomy (pLx) without regional node dissection for malignant thyroid nodules. In this study, the long-term postoperative outcome after such insufficient surgical treatment was evaluated. Of 348 patients with differentiated thyroid carcinoma who underwent initial surgery between 1953 and 1976, 84 underwent either Ex or pLx and their records are herein reviewed. The frequency of recurrence from the remnant gland or regional lymph nodes was examined in relation to the tumor diameter (< or = 1.0 cm, tis; 1.0 cm-2.0 cm, t1; > 2.0 cm, t2). After Ex/pLx, the recurrence rate in the tis group was 13.3% and not significantly different from that (13.6%) in the t1 group. The recurrence rate was notably increased in the t2 group. Moreover, there was no significant difference between the recurrence rate in the tis and t1 groups after Ex/pLx and that after lobectomy with nodal dissection. These results suggest that a reoperative procedure with a more extensive thyroidectomy and neck dissection might not necessarily be required immediately after minimal insufficient surgery is inadvertently carried out in patients with small differentiated thyroid carcinoma measuring 2.0 cm in diameter or less.

Adolescent↗

Germline mutations of the APC gene in two Japanese adenomatous polyposis patients.

Germline mutations of the adenomatous polyposis coli (APC) gene have been reported in patients with familial adenomatous polyposis (FAP) and are believed to be an early event in colorectal carcinoma. We report the results of screening for germline mutations of the APC gene in 4 cases of 2 kindreds using non-radioactive PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis. The mutation in kindred 1 was a 4 bp deletion at codon 849 in exon 15, resulting in a frameshift leading to truncation of the APC gene product. In kindred 2, a transversion of C to G at codon 2038 was observed, resulting in an amino acid change from leucine to valine. In this case, it is possible to screen presymptomatic diagnosis easily and quickly by digestion with restriction enzyme EcoNI.

Adenomatous Polyposis Coli↗

Administration of epidural bupivacaine combined with epidural morphine after esophageal surgery.

BACKGROUND: Early tracheal extubation after esophagectomy has been postulated to reduce both morbidity rate and the cost of esophageal surgery. The purpose of this study was to determine the effect of epidural bupivacaine combined with morphine on extubation time, postoperative analgesia, respiration, and hemodynamics in patients undergoing esophagectomy. METHODS: In a randomized double-blind study, twenty patients undergoing esophageal cancer surgery with a thoracoabdominal procedure were studied. All patients received epidural morphine 2 mg at T6-7 and 2 mg at L3-4 at the beginning of wound closure. Then 3 ml/hr continuous epidural administration of either 0.25% bupivacaine (group Bup, 10 patients) or normal saline solution (group NS, 10 patients) through the catheter inserted at T6-7 was continued for 16 hours, followed by low-dose epidural buprenorphine-bupivacaine. RESULTS: The time from end of operation to tracheal extubation was 4.4 +/- 6.7 hours in group Bup and 13.7 +/- 7.1 hours in group NS (p < 0.05). All patients in both groups obtained moderate or adequate pain relief (visual analog scale of 21 +/- 27 mm) without serious side effects. There were no significant differences in visual analog scale, score for pain on a deep breath, blood pressure, heart rate, or respiratory rate between the two groups. CONCLUSIONS: Continuous administration of epidural bupivacaine combined with morphine resulted in good analgesia without any respiratory or hemodynamic depression in patients who had undergone esophagectomy, and early extubation is related to the efficacy of continuous epidural administration of bupivacaine.

Aged↗

Crush syndrome sustained in the 1995 Kobe, Japan, earthquake; treatment and outcome.

STUDY OBJECTIVE: To assess the treatment and outcome of patients with crush syndrome sustained in an earthquake disaster. METHODS: We conducted a retrospective analysis of eight patients with crush syndrome and subsequent acute kidney failure who were treated in the ICU of a university hospital. All eight patients had been extricated from buildings that collapsed in the 1995 Kobe, Japan, earthquake. Crush injury involved the upper extremities in one patient and the lower extremities in seven. Each patient received intravenous fluid infusion and diuretic drugs and underwent hemodialysis. Emergency fasciotomy was performed in some patients, 17 to 100 hours after extrication. RESULTS: All patients were conscious and lucid on admission, and blood pressure and heart rate were normal. All the patients demonstrated kidney failure with increased concentrations of serum creatinine (1.9 to 9.6 mg/dL [169 to 852 mumol/L]). Six patients were oliguric. Hyperkalemia (5.6 to 8.8 mEq/L) was present in six patients. We found close correlations between the serum potassium and creatine kinase concentrations, between the serum myoglobin and potassium concentrations, and between the serum myoglobin and creatine kinase concentrations. All the patients were weaned from hemodialysis. The serum creatinine concentration decreased to a normal level within 20 to 52 days of admission in all patients. No patients underwent amputation. Muscle weakness and sensory deficits persisted in all patients 6 months after the earthquake. CONCLUSION: Our findings support current therapeutic strategies for crush syndrome, despite the long delay to initiation of intensive therapy. All the patients recovered kidney function and were weaned from hemodialysis; none required amputation.

Acute Kidney Injury↗

Lidocaine-induced hemodynamic effects are enhanced by the inhibition of endothelium-derived relaxing factor in dogs.

BACKGROUND: Lidocaine has been shown to have direct vasoconstrictive effects at low concentrations. Since lidocaine inhibits endothelium-dependent vasodilation in vitro, the vasoconstrictor effect of lidocaine may be due to inhibition of endothelium-derived relaxing factor(EDRF/NO). Therefore, the current study was designed to determine the effects of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide synthase, on systemic and pulmonary hemodynamics during lidocaine infusion. METHODS: Systemic and pulmonary hemodynamic effects of lidocaine infusion, 1 mg.kg-1.min-1, for 10 min were measured in dogs anesthetized with 1% halothane in oxygen. Dogs were studied twice with an interval of 1 week in a cross-over study, and were assigned to one of two groups that received saline or L-NNA intravenously in group 1 (n = 8), or L-NNA or L-NNA + L-arginine which reverses the nitric oxide synthesis inhibitor effect of L-NNA, intravenously in group 2 (n = 8) prior to lidocaine infusion. The free serum concentration of and protein-binding ratio for lidocaine were measured. RESULTS: With saline pretreatment in group 1, lidocaine infusion significantly decreased cardiac index (CI) and significantly increased mean pulmonary arterial pressure (MPAP), pulmonary arterial occlusion pressure (PAOP), systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR). L-NNA pre-treatment in group 1 significantly enhanced the changes in CI, MPAP, PAOP, SVR and PVR during lidocaine infusion. In group 2, L-arginine infusion partially offset the additive effects of L-NNA to the depressive effects of lidocaine. There were no significant differences in free serum concentration of or protein-binding ratio for lidocaine among the groups. CONCLUSION: In contrast to in vitro study, vasoconstrictor effect of lidocaine is enhanced when a capacity for compensatory vasodilation including EDRF/NO pathway is exhausted in halothane-anesthetized dogs.

Anesthetics, Local↗

Development of Graves' disease after surgical treatment for thyroid nodules: report of four cases.

We report herein rare cases who developed hyperthyroid Graves' disease after surgical treatments for thyroid nodules. We have seen only 4 such cases in the course of 1680 consecutive cases (0.24%) of thyroidectomies in which partial thyroidectomy was carried out from 1966 to 1993. It is of interest that because 2 of these three cases (67%) were associated with positive TGHA and/or MCHA at the time of surgery, the presence of autoimmune thyroiditis may predispose to Graves' disease, but surgical treatment of the thyroid glands may not be related to the development of Graves' disease, because the hyperthyroid symptoms appeared 2 to 27 years (mean: 12 years) after the surgery.

Adult↗

Cyclothialidine analogs, novel DNA gyrase inhibitors.

DNA gyrase inhibitors, cyclothialidines B, C, D and E were isolated from four Streptomycete strains (NR 0659, NR 0660, NR 0661 and NR 0662). Their structures have been elucidated based on the amino acid analysis of the hydrolysates, NMR and HRFAB-MS experiments and shown to be cyclothialidine analogs. The absolute stereochemistry has been determined by the chiral HPLC analysis of the hydrolysates. Cyclothialidines B, D and E are novel and potent inhibitors of DNA gyrase.

Chromatography, High Pressure Liquid↗

[The effects of vasoconstrictors on distribution of ischemic tissue flow in isolated perfused rat liver].

We studied the effects of ATP and epinephrine on distribution of ischemic hepatic tissue flow in the isolated perfused rat liver. Five minutes after clamping both the portal vein and hepatic artery, perfusion was started. Lidocaine was infused into the portal vein, and the concentration of lidocaine in hepatic outflow was measured with FPIA. The oxygen extraction ratio was also measured. Tissue surface blood flow was measured with laser-Doppler flowmetry. We measured the tissue flow at 2 points: one where flow was more than 10 ml.min-1.100 gm liver weight-1 (R), and the other where flow was less than 10 ml.min-1.100 gm liver weight-1 (P). After perfusion pressure had become stable, ATP or epinephrine was infused for 15 minutes. Perfusion pressure increased, and tissue flow of R decreased significantly, while that of P increased (not significantly). The extraction ratio of lidocaine decreased significantly by epinephrine, and that of oxygen decreased (not significantly). We conclude that in the ischemic liver, vasoconstriction results in changes in the distribution of tissue blood flow and alters drug metabolism.

Adenosine Triphosphate↗