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Biomedical subjects

Y Fujiwara

Publications and source records attributed to Y Fujiwara.

At least 235 records · Page 13Linked to original sources

Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to clarify the risk factors for morbidity as well as to establish an optimum surgical strategy for hepatocellular carcinoma (HCC). METHODS: The risk factors linked to postoperative complications were analysed in 388 patients over a 10-year period, according to the kind of operative procedure. RESULTS: Stepwise regression analysis revealed that the most important factors related to postoperative morbidity were: age, creatinine level and the histological grade of fibrosis for the bisegmentectomy; the presence of diabetes mellitus, blood urea nitrogen level, the indocyanine green dye retention rate at 15 min and blood loss for the segmentectomy; the presence of diabetes mellitus and blood loss for subsegmentectomy; the presence of diabetes mellitus, the aspartate aminotransferase level, and the total operating time for resection less than subsegmentectomy. CONCLUSION: The most important risk factors were not always related to liver function tests, but instead to other coexisting conditions such as diabetes mellitus and operation stress including operating time and blood loss. Therefore, any future treatment strategy of hepatic resection for HCC should make every effort both to evaluate coexisting conditions carefully and to reduce operative stress as far as possible.

Age Factors↗

Power spectral analysis of variations in heart rate in patients with hyperthyroidism or hypothyroidism.

Power spectral analysis (PSA) of the variation in heart rate is useful in determining the relative activity of the sympathetic and parasympathetic nerves. In this study, PSA was used to investigate the relationship between abnormalities in autonomic nerve function and the presence of thyroid disorders in patients with autoimmune thyroid diseases. The low frequency (LF) or high frequency (HF) components of R-R variations were determined by PSA. The coefficient of variation of the R-R time intervals (CV(R-R)) was positively correlated with HF in healthy subjects. In untreated hyperthyroid patients with Graves' disease, the CV(R-R) and HF values were significantly lower than in healthy controls. Moreover, the LF/HF ratio in patients with untreated Graves' disease was significantly higher, and the LF/HF ratio in hypothyroid patients with Hashimoto's thyroiditis was significantly lower than in healthy controls. A negative correlation was observed between serum levels of free thyroid hormones (FT4 and FT3) and HF in Graves' disease patients. In some hyperthyroid patients, antithyroid drug therapy or beta-blocker administration gradually restored reduced HF values. Present results suggest that relative vagal nerve activity is reduced in hyperthyroid patients and that this reduction is reversible according to the decrease in serum levels of thyroid hormones.

Adrenergic beta-Antagonists↗

Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma.

OBJECTIVE: The aims of this study were to identify prognostic factors in patients who developed recurrent hepatocellular carcinoma (HCC) after repeat hepatectomy and to elucidate the role of multicentric occurrence in the second tumor after a first hepatectomy. SUMMARY BACKGROUND DATA: A repeat hepatectomy for recurrent HCC has been established as the most effective treatment modality, whenever it is possible. However, the prognostic factors for recurrent HCC after repeat hepatectomy have yet to be clarified. METHODS: Forty-one patients who underwent a curative repeat hepatectomy were retrospectively studied. Patient survival and disease-free survival after recurrence were univariately and multivariately analyzed using 38 clinicopathologic variables. The histologic grade of HCC at repeat hepatectomy was also compared with that at first hepatectomy. RESULTS: Patient survival after repeat hepatectomy did not differ substantially from that in 312 patients undergoing primary hepatectomy. However, the disease-free survival after repeat hepatectomy was significantly lower than that in patients with only a primary hepatectomy (p < 0.05). Multivariate analysis revealed only portal vein invasion in the first hepatectomy to be an independent and significantly poor prognostic factor. Regarding multicentric occurrence at repeat hepatectomy, only 6 of 40 patients (15%) whose specimens could be evaluated histologically were determined to be Edmondson and Steiner's Grade 1. CONCLUSIONS: The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.

Algorithms↗

Comparison of early- and late-onset rapid cycling affective disorders: clinical course and response to pharmacotherapy.

This study compared the clinical course and response to pharmacotherapy of patients with rapid cycling affective disorder (RCAD). A retrospective study was conducted on outpatients with affective disorder from 1991 to 1992 at Okayama University Medical School to select cases of RCAD. The subjects were 35 patients who fulfilled DSM-III-R criteria for mood disorder and had experienced at least four episodes of illness during the previous year. The subjects were divided into two groups according to their age at the first phase of affective illness: an early-onset group, consisting of patients aged 25 years or younger, and a late-onset group, consisting of patients aged 26 or older. There were 14 patients in the early-onset group and 21 in the late-onset group. Both the mean duration from onset to rapid cycling and the mean duration of each phase were shorter in the early-onset group than in the late-onset group. There were no significant differences between the groups in period of remission, character of the first episode, heredity, or thyroid function. Lithium carbonate therapy was more effective for reducing manic symptoms in the late-onset group than in the early-onset group, without maintaining a prophylactic effect in either group, whereas carbamazepine was more effective in the early-onset group. Antidepressants used in the depressive phase had a tendency to be more effective in the late-onset than in the early-onset group. However, rapid cycling induced by antidepressants was more evident in the late-onset than in the early-onset group. These findings supported the differentiation of RCAD into two groups based on age at onset, the early-onset group showing a rapid cycling course at an early stage and a good response to carbamazepine, the late-onset group having a relatively long disease duration until the appearance of a rapid cycling course and a good response to lithium carbonate in the manic phase and to antidepressants in the depressive phase.

Adolescent↗

Prostaglandins in the stomach: an update.

Prostaglandins (PGs) are responsible for regulation of various physiologic activities in many tissues and organs, including the stomach. Recent studies have shown new crucial roles of PGs in the stomach. Activation of inflammatory cytokines and neutrophils may cause acute gastric mucosal lesions and recurrence of ulcers, which are induced by noxious stimuli such as nonsteroidal antiinflammatory drugs (NSAIDs), stress and Helicobacter pylori (H. pylori). These phenomena are PG-dependent because exogenous PGs reverse them. PG deficiency and H. pylori may worsen the quality of ulcer healing in terms of inflammatory responses, which are related to future ulcer recurrence. Neutrophils, monocytes/macrophages, and adhesion molecules are involved in the mechanism of recurrence caused by inflammatory cytokines. PGs accelerate ulcer healing, possibly via angiogenesis, epithelial cell proliferation, production of growth factors such as hepatocyte growth factor and transforming growth factor beta, reconstruction of extracellular matrices, and suppression of inflammatory cell infiltration, in addition to gastroprotective mechanisms. The PG synthase cyclooxygenase (COX) has two forms, COX-1 and COX-2. COX-2, but not COX-1, contributes to ulcer healing. Moreover, recent studies suggest the involvement of COX-2 in development of gastric and colon carcinoma. This may be linked to the chemopreventive effect of NSAIDs.

Humans↗

Differential expression of DNA topoisomerase II alpha and II beta genes between small cell and non-small cell lung cancer.

DNA topoisomerase II (Topo II) inhibitors are widely used in lung cancer chemotherapy, but small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) show different sensitivity to them. In this study, we examined the gene expression levels of both isoforms of Topo II (II alpha and II beta) in lung cancer specimens to investigate the differential expression between SCLC and NSCLC. The expression levels of the Topo II alpha and Topo II beta genes were assessed in 80 autopsy samples (40 primary tumors and 40 corresponding normal lung tissues) by using the reverse transcription polymerase chain reaction. We found that the expression levels of the Topo II alpha gene in tumors were significantly higher than those in normal lung tissues, and that those in SCLC were significantly higher than those in NSCLC. There were no significant differences in Topo II beta gene expression between tumors and normal lung tissues and between SCLC and NSCLC. Further-more, correlation analysis revealed that Topo II alpha expression was correlated with Topo II beta expression in both tumor and normal lung tissues. These results indicate that a difference exists in the regulation of the Topo II gene between lung tumors and normal lung tissues. Our finding of differential expression of Topo II alpha between SCLC and NSCLC also suggests that the Topo II alpha expression level is associated with sensitivity to Topo II inhibitors.

Adult↗

A prospective comparative trial of a gonadotropin-releasing hormone analogue with clomiphene citrate for the treatment of oligoasthenozoospermia.

BACKGROUND: We undertook a prospective trial to compare the efficacy and adverse effects of a gonadotropin releasing-hormone analogue (GnRHa) and clomiphene therapy for idiopathic normogonadotropic oligoasthenozoospermia (INOA). METHODS: Between January and December 1995, 44 newly-diagnosed INOA patients were randomly allocated to treatment with GnRHa or clomiphene citrate. Efficacy was assessed by measuring changes in semen parameters prior to and after 3 months of treatment. Twenty-three INOA patients underwent GnRHa therapy with 15 microg of diluted buserelin acetate given once a day intranasally, and 21 INOA patients were treated with 50 mg of clomiphene citrate daily by oral administration. RESULTS: The mean sperm density in the GnRHa group increased from 16.1 x 10(6)/mL to 26.9 x 10(6)/mL (P < 0.05), while the mean sperm density did not change significantly in the group treated with clomiphene. Similarly, the mean sperm motility increased from 35.9% to 43.9% in the GnRHa group (P < 0.05), but did not significantly change in the clomiphene group. No adverse effects were observed in either group. CONCLUSION: This GnRHa treatment protocol can be administered as an outpatient and is hoped to benefit INOA patients.

Administration, Intranasal↗

Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells.

Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from human pheochromocytoma, is present in the kidney and secreted from endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM is still unclear. To clarify the significance of AM as a local regulator, we investigated its secretion and action in cultured cells, and examined the effects of neutralization using a specific monoclonal antibody against AM. The prepared antibody directed against the ring structure showed a high affinity for human and rat AM. Using radioimmunoassay with this antibody, we found significant secretion from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from EC and VSMC. The addition of AM into cultured cells dose-dependently increased cAMP production and potently inhibited PDGF-stimulated thymidine incorporation. Pretreatment with the monoclonal antibody completely abolished cAMP increase induced by exogenous AM. Moreover, antibody neutralization of endogenously secreted AM in cultured EC, but not in MC or VSMC, markedly (by approximately 70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA synthesis. These results indicate that AM, acting as an autocrine/paracrine regulator, exerts an antiproliferative action on EC and MC, and suggest its role as a local modulator of endothelial and mesangial function.

Adrenomedullin↗

Gastroesophageal reflux after distal gastrectomy: possible significance of the angle of His.

OBJECTIVE: We investigated whether the angle of His influences gastroesophageal reflux after distal gastrectomy. METHODS: Thirty-eight patients having distal gastrectomy and 10 controls underwent upper gastroesophageal fluoroscopy to measure the angle of His, and gastroesophageal reflux was assessed by scintigraphy. The association between scintigraphic reflux and the angle of His was then evaluated. RESULTS: In distal gastrectomy patients with and without reflux symptoms, the angle was 108.82 +/- 21.88 degrees and 96.07 +/- 13.25 degrees, respectively; it was 74.14 +/- 10.85 degrees in the controls. The angle was significantly larger in the patients than in the controls (p < 0.01). In addition, the angle in the symptomatic gastrectomy group tended to be larger than in the asymptomatic group. The angle was also significantly larger in patients with a scintigraphic reflux index > or =6% than in those with an index <6% (p < 0.05). CONCLUSIONS: These findings suggest that the angle of His plays a role in reflux after distal gastrectomy and that the severity of reflux may be estimated by measuring this angle.

Adult↗

Indomethacin interferes with EGF-induced activation of ornithine decarboxylase in gastric cancer cells.

BACKGROUND/AIMS: Epidermal growth factor (EGF) has a wide variety of biological activities in the protection of gastric mucosa against acute injury and the healing of gastric ulcer. However, the molecular basis of the EGF action remains unknown. EGF-induced activation of ornithine decarboxylase (ODC) was examined, because ODC is a key enzyme for the cell proliferation. METHODS: The effects of epidermal growth factor (EGF) and indomethacin on ornithine decarboxylase (ODC) mRNA and enzyme activity were examined in gastric cancer derived KATO-III cells. RESULTS: EGF induced both ODC mRNA expression and enzyme activation in a biphasic manner with the peaks at 0.5 and 3 h for mRNA and at 5 and 9 h for enzyme activity, respectively. Indomethacin pretreatment significantly reduced EGF-induced ODC activation and was completely abolished for the first 5 h. CONCLUSION: Since it has been reported that both EGF and ODC are involved in cell migration and proliferation, two actions of EGF for gastric mucosal healing may be through, at least in part, this biphasic activation of ODC. Indomethacin suppresses and changes the response of ODC induced by EGF.

Adenocarcinoma↗

Augmentation of mitochondrial reduced glutathione by S-adenosyl-L-methionine administration in ischemia-reperfusion injury of the rat steatotic liver induced by choline-methionine-deficient diet.

We examined whether warm ischemia-reperfusion (I/R) damage of the rat steatotic liver can be reduced by administration of S-adenosyl-L-methionine (SAMe). We examined the effect of SAMe on the mitochondrial reduced-glutathione (GSH) pool. Sixty minutes of partial left lobar vascular clamping followed by 2 h of reperfusion were employed for a model of hepatic warm ischemia. Either 5% dextrose or SAMe was injected intraperitoneally 2 h before I/R in steatotic rats (S-D5% or S-SAMe group). Serum liver enzyme concentrations 2 h after reperfusion were significantly lower in the S-SAMe group than in the S-D5% group. The cytosolic and mitochondrial GSH concentrations after I/R were significantly higher in the S-SAMe group than in the S-D5% group (p < 0.05). The cytosolic and mitochondrial oxidized-glutathione/GSH ratios after I/R were significantly greater in the S-D5% group than in the S-SAMe group (p < 0.01). The adenosine triphosphate concentration was higher in the S-SAMe group than in the S-D5% group (p = 0.0515). These results show that hepatocellular and mitochondrial oxidative stress after I/R in the steatotic liver can be reduced by administration of SAMe. The results also show that mitochondrial function and hepatocellular integrity can be restored by administration of SAMe in steatotic rats.

Animals↗

Scintigraphic assessment of double tract reconstruction after total gastrectomy.

BACKGROUND/AIMS: This study was carried out to evaluate the clinical significance of double tract reconstruction after total gastrectomy. METHODS: 25 patients, 14 with jejunal pouch double tract reconstructions and 11 with rho-double tract reconstructions, were studied. Scintigraphy was used to evaluate duodenal and jejunal passage, and the jejunal/duodenal ratio was calculated. The patients were classified into 3 groups based on this ratio: group A (n = 14) ratio <1; group B (n = 6) ratio 1-2, and group C (n = 5) ratio >2. The reflux score, scintigraphic reflux index, emptying time of the jejunal pouch or rho-limb, and various nutritional parameters were compared between the 3 groups. RESULTS: The emptying time was shortest in group B, but there was no significant difference among the 3 groups in the Sigstad dumping scores. The reflux score, scintigraphic reflux index, and most nutritional parameters also showed no significant differences between the 3 groups. Leakage at the duodenojejunostomy did not occur in any patient. CONCLUSION: Our findings suggest that there was no preferential passage via the duodenum or jejunum after double tract reconstruction. This method is also useful for decompression of the duodenal stump and group B seemed to have the ideal reconstruction on the basis of emptying time.

Adult↗

Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group.

PURPOSE: Irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC) as monotherapy. Cisplatin is also a key drug against SCLC. We conducted a phase II study of CPT-11 combined with cisplatin to evaluate the efficacy and toxicity of this regimen in patients with previously untreated SCLC. PATIENTS AND METHODS: Seventy-five patients with previously untreated SCLC were enrolled onto the study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1 every 28 days. Four courses of chemotherapy followed by thoracic irradiation were given to patients with limited disease (LD) and six courses to patients with extensive disease (ED). RESULTS: The overall response rate was 84%, with a complete response (CR) rate of 29%. Forty patients with LD achieved an overall response rate of 83% and a CR rate of 30% and 35 patients with ED achieved an overall response rate of 86% and a CR rate of 29%. The median response duration was 8.0 months for LD patients and 6.6 months for ED patients. The median survival was 14.3 months for LD patients and 13.0 months for ED patients. The major grade 3 or 4 toxicities were neutropenia (77%), leukopenia (45%), diarrhea (19%), and anemia (39%). Two patients died with concomitant neutropenia and diarrhea. CONCLUSION: This is a new active regimen for SCLC, especially ED-SCLC, with acceptable toxicity. A phase III study that compares CPT-11/cisplatin with etoposide/cisplatin for ED-SCLC is now being conducted.

Adult↗

Power spectral analysis of heart rate variation in diabetic patients with neuropathic foot ulceration.

OBJECTIVE: To evaluate the relationship between diabetic autonomic neuropathy and diabetic neuropathic foot ulceration, we used power spectral analysis (PSA) of heart rate variation, which provides the accurate simultaneous quantification of parasympathetic and sympathetic activities, to assess autonomic function in diabetic patients. RESEARCH DESIGN AND METHODS: We studied 55 NIDDM patients including 10 diabetic patients without neuropathy, 23 diabetic patients with neuropathy and no history of foot ulceration, and 22 diabetic patients with neuropathic foot ulceration. We performed PSA of 100 R-R intervals at rest and analyzed the results by fast Fourier transformation. RESULTS: The low frequency (LF) power, which reflects sympathetic activity, and the high frequency (HF) power, which reflects parasympathetic (vagal) activity, were inversely correlated with the duration of diabetes and the fasting plasma glucose (FPG) levels. By multiple regression analysis, the FPG remained with significant influence on both LF and HF powers. The LF and HF powers were positively correlated with motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) in the upper and lower limbs and the coefficient of variation of R-R intervals. The LF and HF powers were significantly reduced in patients with neuropathy and patients with foot ulceration compared with patients without neuropathy. Although the median MCV and SCV were similar between diabetic patients with neuropathy and patients with foot ulceration, both the LF and HF powers were significantly decreased in patients with foot ulceration compared with patients with neuropathy. There was no difference in the value of the LF:HF ratio, an index of sympathovagal balance, among three subgroups. We observed a positive correlation between LF and HF power in all subjects; however, the LF and HF powers were not correlated in the subgroups of patients with foot ulceration. CONCLUSIONS: These results showed that diabetic patients with neuropathic foot ulceration have a greater impairment in spectral indexes of autonomic activity obtained by PSA than patients with neuropathy and no history of foot ulceration, whereas no difference was present in nerve conduction velocities.

Age Factors↗

A candidate high density lipoprotein (HDL) receptor, HB2, with possible multiple functions shows sequence homology with adhesion molecules.

High density lipoprotein (HDL), an antiatherogenic lipoprotein comprises several subclasses differing in composition and metabolic function. This physiological complexity appears to be matched with the growing number of candidate HDL receptors, since several HDL binding proteins have recently been identified in various tissues. Because these putative receptors may signal different pathways it is important to identify their structure and potential role in HDL metabolism. We review recent progress in the cloning and characterization of HB2, one of a pair of HDL binding proteins (HB1 and HB2) first purified from rat liver. The structure of HB2 is consistent with a receptor role for this membrane protein and when expressed in cells, increases HDL binding 2 fold. HB2, minimally present in THP-1 cells, is substantially upregulated in macrophages and appears sensitive to cholesterol loading of these cells. The protein shows high homology with adhesion molecules ALCAM and BEN and the possibility that HDL by binding to HB2, reduces adhesion induced arterial wall injury, is discussed in the context of the known protective role of HDL against atherosclerosis. The possible functions of HB2 are also compared with other recently cloned HDL receptors.

Animals↗

Circulating thrombomodulin and hematological alterations in type 2 diabetic patients with retinopathy.

To clarify the relationship between circulating thrombomodulin (TM) and endothelial cell damage in diabetes mellitus, plasma levels of TM were quantitated by an enzyme linked immunoabsorbant assay (ELISA) in 164 type 2 diabetes mellitus and 72 normal control subjects, and these levels were compared with those of von Willebrand factor antigen (vWf: Ag), thrombin antithrombin III complexes (TAT), plasmin-alpha2-plasmin inhibitor complexes (PIC), fibrinogen, D-dimer, urinary albumin excretion rate (AER), intima-media thickness (IMT) and plaque score of the common carotid artery assessed with high resolution B-mode ultrasonography. Plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and plaque score were significantly increased in the diabetic patients compared to the normal control subjects. Plasma TM levels showed significant correlation with vWf: Ag (r=0.350, p<0.0001), TAT (r = 0.334, p < 0.0001), PIC (r = 0.450, p < 0.0001), AER (r = 0.334, p < 0.0001), IMT (r = 0.181, P<0.01), plaque score (r=0.385, p<0.0001). Among four groups of diabetic patients, divided based on their severity of diabetic retinopathy, there were no significant differences in age, sex, systolic and diastolic blood pressure levels, HbA,1c, or plasma lipid levels, although the plasma levels of TM, vWf: Ag, TAT, PIC, AER, IMT and the plaque score in the patients with proliferative retinopathy were significantly higher than those of the healthy controls and patients with simple retinopathy. Among the 43 normoalbuminuric patients without intima-media thickness or thickened plaque (AER<30 mg/g Creatinine, IMT<1.0 mm, plaque score = 0), plasma levels of TM, vWf: Ag, TAT, PIC were significantly higher in those patients with retinopathy than in those without retinopathy. Multivariate analysis showed TM, TAT and PIC levels to be independent predictors of diabetic retinopathy. In conclusion, circulating TM reflects endothelial cell damage in patients with diabetic retinopathy, and hypercoagulability might play an important role in endothelial cell damage.

Aged↗

Hyperintense basal ganglia on T1-weighted MR images in a patient with central nervous system lupus and chorea.

We describe a patient with central nervous system lupus and choreatic movements in whom both basal ganglia showed high signal intensity on T1-weighted MR images, while the signal on T2-weighted images remained low. Within 8 months after onset, the choreatic movements had disappeared, with a corresponding decrease in the hyperintense T1 signal. The emergence of the choreatic movement disorder in this patient might have been related to the T1 hyperintensity of the basal ganglia, which, in turn, might have resulted from a vascular insult associated with central nervous system lupus.

Adult↗