Biomedical subjects

K Takenaka

Publications and source records attributed to K Takenaka.

At least 19 recordsLinked to original sources

PubMed1997

Indications for palliative reduction surgery in advanced hepatocellular carcinoma. The use of a remnant tumor index.

OBJECTIVES: To clarify the indications for and the significance of palliative reduction surgery in the multidisciplinary treatment of advanced hepatocellular carcinoma (HCC) and to propose the use of a remnant tumor index (RTI) as a simplified criterion for palliative reduction surgery in cases of advanced HCC. DESIGN: A comparison of survival based on the RTI. SETTING: A large university hospital in Japan. PATIENTS: Twenty-five patients with advanced HCC who underwent palliative reduction surgery were divided into 3 groups as follows: group 1 (n = 9), the remnant tumor after operation existed only in the liver and the RTI was less than 5.0; group 2 (n = 11), the remnant tumor after operation existed only in the liver and the RTI was greater than 5.0; and group 3 (n = 5), extrahepatic metastatic tumor existed after operation. MAIN OUTCOME MEASURES: Pathological findings and survival rate after surgery. RESULTS: There was no significant difference in the degree of macroscopic intrahepatic metastases among the 3 groups; however, both the portal vein invasion and the histological grade tended to be more severe in groups 2 and 3. The respective 1-year and 3-year survival rates for group 1 were 67% and 33%, and those for group 2 were 21% and 0%. There were no survivors in group 3 at 1 year after surgery. Significant differences were found in the survival rates between groups 1 and 2 (P < .05), and between groups 1 and 3 (P < .05). CONCLUSION: Palliative reduction surgery for advanced HCC is only considered effective for patients with both an RTI of less than 5.0 and no extrahepatic metastasis.

Aged↗

PubMed1997

Significance of alpha-fetoprotein levels for detection of early recurrence of hepatocellular carcinoma after hepatic resection.

BACKGROUND: The recurrence of hepatocellular carcinoma (HCC) after surgery is common. The present study was conducted in order to clarify the significance of alpha-fetoprotein (AFP) in the detection of the early recurrence of HCC after surgery. METHODS: Fifty-eight patients who underwent a curative hepatic resection for HCC and whose preoperative AFP levels were >100 ng/ml, were selected for this study. RESULTS: In 26 cases, the postoperative AFP levels within 3 months after surgery did not decrease to <20 ng/ml (high AFP group). In the other 32 cases, the postoperative AFP levels within 3 months after surgery decreased to <20 ng/ml (low AFP group). No significant difference was observed in clinical or pathological backgrounds. The postoperative disease free rate in the low and high AFP groups was 84.2% and 18.4%, at 1 year, 61.2 and 4.6% at 3 years, respectively. The difference was statistically significant (P < 0.01). At the time of recurrence, the AFP levels increased in 25 (96.2%) of the patients who had early recurrence within 1 year after surgery as well as in 11 of 14 (78.5%) who had recurrence >1 year after surgery. The interval from surgery to recurrence significantly correlated with the doubling time of AFP at the time of recurrence in patients with early recurrence (within 1 year after hepatectomy) (r = 0.60, P < 0.01). In cases in which the preoperative AFP level was >100 ng/ml and the postoperative AFP level did not decrease to <20 ng/ml, early recurrence within 1 year after surgery would thus be strongly suspected. CONCLUSION: The measurement of the AFP levels after surgery is therefore considered to be important in the follow-up of hepatectomized patients, especially regarding the detection of early recurrence.

Aged↗

PubMed1997

Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group.

Cytomegalovirus (CMV) infection and CMV-associated disease were monitored using the CMV antigenemia assay in 72 patients who received allogeneic bone marrow transplantation (BMT), and their incidences were compared between related and unrelated donor transplant patients. The incidence of CMV infection after BMT was significantly higher in patients who received transplants from HLA-matched unrelated donors than from HLA-matched sibling donors (87% vs 53%, P < 0.05). CMV-associated disease developed in 73% of unrelated and in 14% of sibling donor transplant patients (P < 0.01). The peak levels of CMV antigenemia were significantly higher in unrelated donors than in sibling donor transplant patients (16 vs 1 CMV antigen-positive cells per 50000 WBCs, P < 0.01). The median number of CMV antigen-positive cells on first detection was also significantly higher in unrelated donor transplant patients (15 vs 1, P < 0.01). The detection of CMV antigen-positive cells preceded the development of CMV-associated disease in 18% of unrelated donor transplant patients, suggesting a lower predictive value of CMV antigenemia for subsequent CMV-associated disease in unrelated donor BMT. Careful monitoring and further studies are needed for the early diagnosis and prevention of CMV-associated disease in unrelated donor BMT.

Adolescent↗

PubMed1997

Clinical evaluation of pulmonary hypertension in systemic sclerosis and related disorders. A Doppler echocardiographic study of 135 Japanese patients.

BACKGROUND: Previous studies on pulmonary hypertension (PH) in systemic sclerosis and related disorders used differing patient populations, and defined PH according to different criteria. We have attempted to determine the prevalence and cause of PH in these disorders using a mainly noninvasive cardiopulmonary evaluation. PATIENTS AND METHODS: One-hundred thirty-five Japanese patients with systemic sclerosis and related disorders were divided into proximal and distal scleroderma groups, with or without overlapping features of systemic lupus erythematosus (SLE) and polymyositis. They underwent multiple cardiopulmonary tests, including chest radiography, pulmonary function tests, and echocardiography to screen for pulmonary fibrosis and PH. RESULTS: The pulmonary artery systolic pressure was estimated by Doppler echocardiography in 80 patients (59%). PH (systolic pressure > or = 40 mm Hg) was diagnosed in 28 patients by the Doppler method and in two patients by right heart catheterization (mean pressure > or = 20 mm Hg). Doppler-estimated pulmonary artery pressures were significantly higher in patients with proximal scleroderma (p < 0.05), and in those with an SLE/polymyositis overlap (p < 0.01). The FVC was significantly reduced in the proximal scleroderma group (p < 0.0005), but not in the overlap group. PH was attributable to pulmonary fibrosis in nine patients who had proximal scleroderma without overlap. Pulmonary arteriopathy was the probable cause of PH in seven patients with overlap and in four patients who had proximal scleroderma without overlap. CONCLUSIONS: These findings suggest that proximal scleroderma predisposes patients to PH mainly because of pulmonary fibrosis, but occasionally because of pulmonary arteriopathy. An overlap of SLE/polymyositis predisposes patients to PH due to the occurrence of arteriopathy.

Asian People↗

PubMed1996

Enhanced coexpression of thioredoxin and high mobility group protein 1 genes in human hepatocellular carcinoma and the possible association with decreased sensitivity to cisplatin.

Thioredoxin (TRX), a disulfide-reducing intracellular protein, functions as a cellular defense mechanism against oxidative stress. In this study, we asked whether expression of TRX, glutathione-thiol transferase pi, and high mobility group protein 1 (HMG-1) genes is enhanced in human hepatocellular carcinoma and whether expression of these genes is associated with sensitivity to cisplatin. Both TRX and HMG-1 were co-overexpressed in almost all cancerous lesions in comparison to normal tissue in surgically resected hepatocellular carcinomas of 20 patients. Tumor sensitivity to cisplatin [cis-diamminedichloroplatinum (II)], but not to mitomycin C or doxorubicin, correlated with mRNA levels of TRX in cancer tissue. TRX and HMG-1 may be useful tumor markers, and TRX might be also a useful marker for sensitivity to cisplatin in human hepatocellular carcinomas.

Adult↗

PubMed1996

Des-gamma-carboxy prothrombin and alpha-fetoprotein positive status as a new prognostic indicator after hepatic resection for hepatocellular carcinoma.

BACKGROUND: The aim of this study was to elucidate the usefulness of measuring the positive status of both des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) preoperatively as a new prognostic indicator of hepatocellular carcinoma (HCC). METHODS: One hundred forty-seven patients who underwent curative hepatic resection for primary HCC were studied. The definitions of DCP and AFP positivity were: positive DCP > 0.1 AU/ml, and positive AFP > 50 ng/ml. The patients were classified into four groups according to their levels of positivity for DCP and/or AFP: Group 1 (n = 59), negative levels of both DCP and AFP; Group 2 (n = 28), negative DCP and positive AFP levels; Group 3 (n = 31), positive DCP and negative AFP levels; and Group 4 (n = 29), positive levels of both DCP and AFP. RESULTS: Patient survival and disease free survival in Group 4 were the worst among the four groups. By multivariate analysis, using Cox proportional hazards model, both the DCP- and AFP-positive status (in combination) and poorly differentiated histology were independent factors of poor prognosis for patient survival; and DCP- and AFP-positive status (in combination), poorly differentiated histology, positive intrahepatic metastasis, and tumor diameter over 5 cm were independent factors of poor prognosis for disease free survival. CONCLUSIONS: The combination of DCP- and AFP-positive status is a new prognostic indicator for patients with HCC after hepatic resection.

Adult↗

PubMed1996

In vitro expansion of hematopoietic progenitor cells induces functional expression of Fas antigen (CD95).

Fas antigen (Fas Ag; CD95) is a cell surface molecule that can mediate apoptosis. Bcl-2 is a cytoplasmic molecule that prolongs cellular survival by inhibiting apoptosis. To investigate the role of both molecules in hematopoiesis, we evaluated the expression of Fas Ag and Bcl-2 on CD34+ hematopoietic progenitor cells expanded in vitro. CD34+ cells isolated from bone marrow were cultured in iscove's modified Dulbecco's medium supplemented with 10% fetal calf serum, 1% bovine serum albumin, 50 ng/mL stem cell factor, 50 ng/mL interleukin-3 (IL-3), 50 ng/mL IL-6, 100 ng/mL granulocyte colony-stimulating factor, and 3 U/mL erythropoietin for 7 days. Colony-forming unit of granulocytes/macrophages (CFU-GM) and burst-forming unit of erythroids (BFU-E) were expanded 6.9-fold and 8.8-fold in number at day 5 of culture, respectively. Freshly isolated CD34+ cells did not express Fas Ag, whereas approximately half of them expressed Bcl-2. CD34+ cells cultured with hematopoietic growth factors gradually became positive for Fas Ag and rapidly lost Bcl-2 expression. Furthermore, apoptosis was induced in the cultured CD34+ population when anti-Fan antibody (IgM; 1 microgram/mL) was added, as shown by significant decrease in the number of viable cells, morphologic changes, induction of DNA fragmentation, and significant decrease in the number of clonogenic progenitor cells including CFU. GM and BFU-E. These results indicate that functional expression of Fas Ag is induced on CD34+ cells expanded in vitro in the presence of hematopoietic growth factors. Induction of Fas Ag and downregulation of Bcl-2 may be expressed as part of the differentiation program of hematopoietic cells and may be involved in the regulation of hematopoiesis.

Adult↗

PubMed1996

Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia.

The leukemia-specific AML1/ETO fusion gene has been shown to be detected by reverse transcriptase polymerase chain reaction (RT-PCR) analysis in patients with t(8;21) acute myelogenous leukemia (AML) in long-term remission. In the present study, the AML1/ETO mRNA could be detected by RT-PCR in bone marrow (BM) and/or peripheral blood (PB) samples from all 18 patients who had been maintaining complete remission for 12 to 150 months (median, 45 months) following chemotherapy or PB stem cell transplantation (PBSCT), whereas it could not be detected in four patients who had been maintaining remission for more than 30 months following allogeneic BM transplantation (BMT). We surveyed the expression of AML1/ETO mRNA in clonogenic progenitors from BM in these cases. Notably, 51 of 2,469 colonies from clonogenic progenitors (2.1%) expressed the AML1/ETO mRNA in 18 cases who were RT-PCR+ in BM and/or PB samples. Expression was observed in various clonogenic progenitors, including granulocyte-macrophage colonies, mixed colonies, erythroid colonies, and megakaryocyte colonies. Furthermore, we analyzed the clonality of these progenitors by X-chromosome inactivation patterns of the phosphoglycerate kinase (PGK) gene in four female patients. The AML1/ETO mRNA+ progenitors showed the PGK allele identical to that detected in the leukemic blasts from the time of initial diagnosis. Normal constitutive hematopoiesis was sustained by polyclonal BM reconstitution in these patients. Accordingly, these committed progenitor cells that express AML1/ETO mRNA during remission likely have arisen from common t(8;21)+ pluripotent progenitor cells with at least trilineage differentiation potential. These data strongly suggest that the origin of the clonogenic leukemic progenitors of t(8;21) AML may be multipotent hematopoietic progenitors that acquired the t(8;21) chromosomal abnormality.

Adult↗

PubMed1996

Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma.

BACKGROUND: Recurrence of small hepatocellular carcinoma (HCC) is common. Recent studies have suggested that the status of the underlying liver parenchyma is a significant risk factor for recurrence of HCC. METHODS: The postoperative values of transaminase were examined every 6 months after surgery in 57 patients with a surgically resected solitary small HCC measuring up to 3 cm in greatest dimension. Based on the patterns of the transaminase values, the patients were divided into two groups. Group 1 (n = 20) had a high transaminase level; the values of postoperative transaminase were always more than 100 IU/L. Group II (n = 37) had a low transaminase level; the values of postoperative transaminase were sometimes lower than 100 IU/L. RESULTS: The cumulative carcinoma-free survival rates in Groups I and II were 91% and 80%, respectively, at 1 year, 64.5% and 5.5%, respectively, at 3 years, and 48.2% and 0%, respectively, at 5 years after surgery. The disease free survival rates in Group I were significantly lower than those in Group II (P = 0.0007), although no significant differences in histologic risk factors for recurrence or in clinical backgrounds were observed. With regard to the recurrence pattern, solitary recurrence was more frequently observed in Group I (P = 0.02), compared with the patients in Group II. A histologic comparison between the primary and recurrent tumor in patients who underwent re-resection for solitary recurrence demonstrated the possible multicentric occurrence of HCC in 2 of 8 patients (25%) in Group I. CONCLUSIONS: This study suggests that the hepatitis status of the remnant liver plays an important role in the recurrence rates and patterns of small HCC after hepatectomy.

Carcinoma, Hepatocellular↗

PubMed1996

Spindle cell hepatocellular carcinoma. A clinicopathologic and immunohistochemical analysis of 15 cases.

BACKGROUND: Spindle cell hepatocellular carcinoma (SpHCC) has rarely been reported, and its clinicopathologic characteristics, histogenesis, and prognosis after hepatic resection have yet to be clarified. METHODS: Fifteen cases of SpHCC, including 13 surgically resected patients and 2 autopsy cases, were studied clinicopathologically and immunohistochemically. RESULTS: In 13 resected patients, all except 1 were male and the serum alpha-fetoprotein (AFP) was positive in 6 (46%). Portal venous invasion and intrahepatic metastases were frequent. In an immunohistochemical analysis of 13 SpHCC tumors, cytokeratin CAM 5.2 and AFP were positive in 8 (62%) tumors and 3 (23%) tumors in both ordinary HCC and spindle cell components, respectively. The spindle cell components, but not ordinary HCC components, revealed a positive reaction for vimentin in 8 (62%) tumors, S-100 protein and HAM-56 in 3 (23%) tumors, HHF-35 in 2 (15%) tumors, and alpha-smooth muscle actin, desmin, and KP-1 in 1 (8%) tumor, respectively. p53 overexpression was found in two SpHCC tumors. The survival curve after hepatic resection in the 13 patients with SpHCC was significantly worse than that of the 371 patients with Stage II-IV ordinary HCC (P < 0.001). CONCLUSIONS: These results suggest that SpHCC represents a sarcomatous transformation of HCC. The spindle cell components revealed an immunohistochemical expression of several markers of mesenchymal cells. In addition, poor survival after hepatic resection was documented.

Adult↗

PubMed1996

Results of 280 liver resections for hepatocellular carcinoma.

OBJECTIVE: To evaluate the recent results of liver resection in patients with hepatocellular carcinoma. DESIGN: Retrospective study. SETTING: A university hospital in Japan. PATIENTS: Two hundred eighty patients who underwent liver resection with complete extirpation of hepatocellular carcinoma from 1985 to 1993. MAIN OUTCOME MEASURES: Morbidity and survival after operation and the pathologic features of hepatocellular carcinoma according to the TNM classification of the International Union Against Cancer. RESULTS: More than 40% of the patients with stages I and II disease underwent a partial resection of the liver, whereas 50% of those with stages III and IVA were operated on with more than a bisegmentectomy. Fifty percent of all patients had no postoperative complications. The morbidities included intra-abdominal abscess (7%), bile leakage (5%), and hepatic failure (4%, of whom half died; mortality rate, 2%). Histopathologically, 32% of the stage I tumors were well differentiated (grade 1), while, in stage III, 56% had portal invasion and 61% had daughter lesions in the liver. The cumulative survival rates of patients with stages I, II, and III disease and all patients at 5 years were 69%, 52%, 32%, and 50%, respectively, while the disease-free survival rates at 5 years were 38%, 34%, 17%, and 29%, respectively. CONCLUSION: The recent results of liver resection for hepatocellular carcinoma are generally satisfactory; however, the recurrence rate is still high.

Aged↗

PubMed1996

Simplified inflow control using stapling devices for major hepatic resection.

We describe the efficacy of a new technique for hepatic inflow division using stapling devices in major hepatic resections. We studied 28 consecutive patients who underwent major hepatic resection at a tertiary referral center by en masse inflow control of Glisson's pedicle in 1993 and 1994, of whom 10 underwent inflow control with stapling devices. Although stapling devices were used for larger tumors (mean +/- SD, 12.2 +/- 8.6 vs 5.7 +/- 5.0 cm; P = .02), the operation time (261 +/- 57 vs 301 +/- 143 minutes), operative blood loss (2071 +/- 1318 vs 4792 +/- 6586 mL), postoperative intra-abdominal bleeding (0% [0/10] vs 17% [3/18]), and hospital stay (16.0 +/- 2.6 vs 20.6 +/- 7.4 days) were favorable for resections with staplers vs resections without staplers; the overall incidences of postoperative complications (40% [4/10] vs 39% [7/18]) and hospital death (10% [1/10] vs 6% [1/18]) were comparable in the two groups. We conclude that stapling devices allow simple, quick, and safe en masse inflow control in major hepatic resections.

Aged↗

PubMed1996

Cardiac complications after hepatic resection.

During a period of 94 months between 1985 and 1993, 474 hepatic resections were performed in 451 patients, of whom 23 (5 per cent) had cardiac problems: ischaemic heart disease in 16 (previous myocardial infarction in five and angina pectoris in 11), arrhythmic disorders in three, valvular disease in three (previous mitral valve replacement in two) and hypertrophic cardiomyopathy in one. The cardiac patients had a higher incidence of cardiac complications (24 versus 0 per cent, P < 0.0001) including two myocardial infarctions, and of non-cardiac complications consisting of postoperative liver failure (16 versus 4 per cent, P < 0.01) and bile leak (16 versus 5 per cent, P = 0.02), as well as hospital death (16 versus 3 per cent, P < 0.001). However, long-term survival was similar in the two groups. Patients with preoperative cardiac conditions appear to be at increased risk for early postoperative morbidity and mortality after hepatic resection.

Adolescent↗

PubMed1996

Hepatitis C virus replication is associated with expression of transforming growth factor-alpha and insulin-like growth factor-II in cirrhotic livers.

The molecular role of hepatitis C virus (HCV) in liver disease has yet to be clarified. In this study, we analyzed the relationship of HCV replication with mRNA expression of growth factors and mutation of tumor suppressor gene, ie, transforming growth factor-beta 1 (TGF-beta 1), which promotes cirrhotic changes; TGF-alpha, insulin-like growth factor-II (IGF-II), which are both related to hepatocyte transformation; and tumor suppressor gene p53, which is associated with HCC progression. A semiquantitative RNA polymerase chain reaction (RNA-PCR) was used to analyze genetic expression in 31 cirrhotic liver specimens from patients with HCV. In order to detect HCV replication, the minus-strand RNA of HCV, which serves as a template for the synthesis of genomic plus-strand RNA, was examined. The expression of the growth factors was semiquantified by RNA-PCR, and the mutation of p53 was detected using PCR-single-strand conformation polymorphism. According to the semiquantitative analysis, HCV replication was not associated with the expression of TGF-beta 1 but was significantly so with the overexpression of TGF-alpha (r = 0.74) and IGF-II (r = 0.65) in the HCV-positive cirrhotic livers. No mutation of p53 was recognized in any of the samples. Our investigation thus suggested that the replication of HCV might mediate the coexpression of TGF-alpha and IGF-II and act as a possible initiating factor for hepatocarcinogenesis.

Actins↗

PubMed1996

Granulocyte colony-stimulating factor-induced mobilization of peripheral blood stem cells for autologous and allogeneic transplantation. Fukuoka Bone Marrow Transplantation Group.

Peripheral blood stem and progenitor cells (PBSC and PBPC), which circulate at very low levels during steady-state hematopoiesis, show a transient but marked increase during hematologic recovery from marrow-suppressive chemotherapy. To ensure rapid and sustained hematologic engraftment after autologous PBSC transplantation, sufficient PBSC or PBPC must be infused. To confirm the utility of granulocyte colony-stimulating factor (G-CSF) in chemotherapy-induced PBSC mobilization, we investigated the effect of G-CSF on PBSC mobilization in leukemia and lymphoma patients. The study design was such that PBSC mobilization with and without G-CSF was assessed in the same patients. The results indicate that PBSC mobilization can be enhanced significantly when G-CSF is given during the recovery phase postchemotherapy. Interestingly, progenitor cells of different lineages could be mobilized by G-CSF. We subsequently investigated the effect of increasing G-CSF dose on PBSC mobilization during steady-state hematopoiesis in healthy adult donors. The results indicate that not only committed but also primitive progenitor cells are mobilized into the circulation in a dose-and time-dependent manner when G-CSF at 5, 10, or 15 micrograms/kg was given on each of 5 days and leukapheresis was performed on day 6. From our data we estimate that sufficient PBSC for engraftment after allogeneic PBSC transplantation can be collected on day 5 of administration of G-CSF at 10 micrograms/kg and by 10-1 leukapheresis on days 5 and 6. Furthermore, we found that some G-CSF-mobilized PBSC retained their self-renewal capability. These observations suggest that hematopoietic stem cells for allogeneic PBSC transplantation can be mobilized by short-term administration of relatively high-dose G-CSF.

Animals↗

PubMed1996

Stability of p53 tumor suppressor gene mutations during the process of metastasis and during chemotherapy.

We analyzed 29 pairs of primary and metastatic lung carcinomas obtained at autopsy for mutations in the p53 gene, using the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP). We examined the relationship between p53 gene mutations and the development of metastasis, and the stability of p53 gene mutations during chemotherapy. The tumors consisted of six small cell carcinomas, 13 adenocarcinomas, eight squamous cell carcinomas, one large cell carcinoma, and one adeno-squamous cell carcinoma. PCR-SSCP analysis showed that three small cell carcinomas (50%), three adenocarcinomas (23%), two squamous cell carcinomas (25%), and one large cell carcinoma (100%) had p53 gene mutations. All these abnormalities were found between exon five and exon eight. The mutations in the primary tumors and the metastatic tumors were identical. These results suggest that p53 gene mutations occur before distant metastases develop, and that they may be stable during the process of metastasis. There were nine metastatic tumor samples that existed before the patients received chemotherapy. These samples showed identical p53 mutations as the corresponding primary tumor. This suggests that anticancer drugs rarely induce p53 gene mutations.

Base Sequence↗

PubMed1996

GABAB-ergic stimulation in hypothalamic pressor area induces larger sympathetic and cardiovascular depression in spontaneously hypertensive rats.

To determine whether central GABA (gamma-aminobutyric acid) B receptor stimulation would affect the sympathetic and cardiovascular activities, baclofen (a GABAB receptor agonist) was injected into lateral cerebral ventricles (intracerebroventricularly, ICV) in urethane-anesthetized normotensive rats. Intracerebroventricular injections of GABAA agonist (muscimol, 1 microgram) consistently decreased blood pressure and heart rate. In contrast ICV injections of baclofen (2 micrograms) increased blood pressure (BP) and heart rate with initial transient cardiovascular depression, and these effects of baclofen were abolished by ICV pretreatment with GABAB antagonist (saclofen, 100 micrograms). To determine whether the cardiovascular effects of ICV injections were elicited by activating GABA receptors in the hypothalamus, we injected baclofen or muscimol directly into various hypothalamic areas. Baclofen (100 and 800 ng) injected into the ventromedial hypothalamus (VMH) or posterior hypothalamus (PH) of normotensive rats produced dose-related decreases in sympathetic nerve activity, blood pressure, and heart rate. These effects of baclofen were larger in VMH injections than in PH injections. The depressor responses elicited by VMH injections of baclofen were abolished by intravenous pretreatment with alpha-blocker, but unaffected by parasympathetic blocker, further indicating that the depressor responses of baclofen (VMH) were not due to parasympathetic activation, but due to peripheral sympathetic depression. Muscimol (400 ng) and baclofen (800 ng) injected into VMH produced similar amplitude of sympathetic-depressant, depressor and bradycardic responses. In contrast, BP was increased by the same dose of baclofen injected into the hypothalamic depressor area (anterior hypothalamus, AH), but was unaffected by muscimol. Final experiments were performed to determine whether these sympathetic and cardiovascular effects to hypothalamic GABAB stimulations would be altered in hypertension. In spontaneously hypertensive rats (SHR), basal BP and heart rate were already higher than in normotensive controls (Wistar-Kyoto rat, WKY). Baclofen injected into VMH reduced sympathetic nerve activity, BP, and heart rate in both groups of rats, and these effects were significantly larger in SHR than in WKY. This enhanced depressor response induced by baclofen (VMH) in SHR persisted even after sinoaortic denervation, which indicates that the enhanced depressor response is not due to reduced peripheral baroreflex sensitivity in SHR. On the other hand, baclofen injected into AH increased BP and heart rate in both WKY and SHR, but the magnitude of these responses did not differ between two groups. In summary, GABA reduces sympathetic nerve activity, BP, and heart rate through both GABAA and B receptors in VMH. The GABAB system acts on the depressor area, AH, to further regulate the cardiovascular activities. In SHR, the GABAB-ergic system in VMH but not in AH is altered, and this might contribute to the development of hypertension.

Animals↗

PubMed1996

Surgical treatment strategy for patients with stage IV hepatocellular carcinoma.

BACKGROUND: This study was conducted to identify the prognostic indicators for patients with stage IV hepatocellular carcinoma (HCC), as well as to clarify the strategy of surgical treatment for those patients. METHODS: Forty-six patients with stage IV HCC were included in this study. Prognostic factors were univariately and multivariately analyzed. Furthermore, the significance of intraoperative treatment for residual tumors was investigated in patients with an absolute noncurative operation. RESULTS: The poor prognostic factors were as follows: host factors, Child's classification of B and C and immunosuppressive acidic protein level of greater than 400 micrograms/ml; tumor factors, tumor diameter of greater than 5 cm, poorly differentiated histologic features, positive portal vein invasion, and intrahepatic metastases involving more than three segments; others, an absolute noncurative operation and no preoperative treatment. Tumor diameter of more than 5 cm was then suggested to be an independent prognostic indicator. Survival of patients with stage IV-A HCC who underwent a curative operation was similar to that of those with stages III HCC: Furthermore, the survival of patients with Stage IV-A who had an absolute noncurative operation but underwent either intraoperative microwave coagulation or ethanol injection to the residual HCCs was not statistically different from that of those with a curative operation. CONCLUSIONS: Therefore for stage IV-A HCC surgical treatment is considered to be both useful and the first choice of treatment when all the tumors in the liver can be removed or when the residual tumors can be treated during operation by either microwave coagulation or ethanol injection as a result of an incomplete removal of the tumors.

Adult↗