The fixed herbal drug composition "Saikokaryukotsuboreito" prevents bone loss with an association of serum IL-6 reductions in ovariectomized mice model.

PURPOSE: Saikokaryukotsuboreito (SRB) is a traditional Japanese herbal medicine that has been used to treat hyperlipidemia. As some studies have shown that lipid-lowering drugs reduce osteoporosis, we investigated the effect of SRB on bone metabolism in the postmenopausal period using an ovariectomized (OVX) murine model. MATERIAL AND METHODS: Fifteen aged 9 weeks female mice were divided into three groups (n=5 each). The OVX group and SRB group underwent bilateral ovariectomy, after which the OVX group was fed a normal diet and the SRB group fed a normal diet containing 2% SRB. The sham group underwent sham surgery and was then fed a normal diet. Eight weeks after surgery, all mice were sacrificed, and bone volume, bone histomorphometric parameters, and bone-associated phenotype were compared among the groups. RESULTS: Compared with the OVX group, the SRB group showed suppression of bone volume loss at the tibia (SRB group: 12.7+/-0.7%, OVX group: 9.8+/-0.4%; p=0.005, ANOVA) and lumbar spine (SRB group: 15.1+/-0.9%, OVX group: 11.3+/-0.1%; p=0.031, ANOVA). A significant decrease in eroded surface was also observed in SRB-treated ovariectomized mice compared with the OVX group (p=0.022, ANOVA). We also found that serum levels of interleukin (IL)-6, a primary mediator of bone resorption, in the SRB group were significantly lower than in the OVX group (SRB: 52.5+/-6.8pg/ml; OVX: 138.0+/-23.1pg/ml; p=0.011, ANOVA). However, unexpectedly, SRB did not affect estradiol and total cholesterol in ovariectomized mice. CONCLUSION: SRB can prevent loss of bone volume and suppress serum IL-6 levels in this postmenopausal model and is a promising candidate for treatment of postmenopausal osteoporosis.

Juzentaihoto (TJ-48), a traditional Japanese herbal medicine, influences hemoglobin recovery during preoperative autologous blood donation and after hip surgery.

OBJECTIVE: Preoperative autologous blood donation is a widely used alternative to allogenic transfusion in hip surgery. However, it has been reported that autologous blood donation may induce preoperative anemia. Juzentaihoto (TJ-48) (Tsumura Co., Tokyo, Japan) is a Japanese herbal medicine that has been used to alleviate anemia. We investigated the effect of TJ-48 on anemia in the perioperative period. PATIENTS AND METHODS: 18 hips of 18 female patients who underwent total hip arthroplasty or rotational acetabular osteotomy (RAO) were divided into two groups. Group A consisted of 9 hips of 9 patients who were treated with TJ-48 at a dose of 7.5 g per day from 21 days before surgery to the day before surgery. Group B consisted of 9 hips of 9 patients who did not take TJ-48. Preoperative autologous blood donation was performed 21, 14 and 7 days before surgery. All patients deposited 400 ml each time for a total of 1,200 ml. Hemoglobin level was recorded on preoperative Days 21, 14 and 7 and postoperative Days 1, 4, 7 and 14. RESULTS: During the preoperative period, repeated measures ANOVA showed a significant difference between the two groups in hemoglobin level (p = 0.04). Despite the lack of TJ-48 after surgery, the rate of hemoglobin decline in Group A was less than in Group B at all examination times. No patients with TJ-48 experienced side effects, including gastrointestinal symptoms and unusual laboratory data. CONCLUSION: TJ-48 is useful for treating anemia during preoperative autologous donation.

Chemotherapy-induced neutropenia as a prognostic factor in advanced non-small-cell lung cancer: results from Japan Multinational Trial Organization LC00-03.

BACKGROUND: Neutropenia is a common adverse reaction of chemotherapy. We assessed whether chemotherapy-induced neutropenia could be a predictor of survival for patients with non-small-cell lung cancer (NSCLC). METHODS: A total of 387 chemotherapy-naïve patients who received chemotherapy (vinorelbine and gemcitabine followed by docetaxel, or paclitaxel and carboplatin) in a randomised controlled trial were evaluated. The proportional-hazards regression model was used to examine the effects of chemotherapy-induced neutropenia and tumour response on overall survival. Landmark analysis was used to lessen the bias of more severe neutropenia resulting from more treatment cycles allowed by longer survival, whereby patients who died within 126 days of starting chemotherapy were excluded. RESULTS: The adjusted hazard ratios for patients with grade-1 to 2 neutropenia or grade-3 to 4 neutropenia compared with no neutropenia were 0.59 (95% confidence interval (CI), 0.36-0.97) and 0.71 (95% CI, 0.49-1.03), respectively. The hazard ratios did not differ significantly between the patients who developed neutropenia with stable disease (SD), and those who lacked neutropenia with partial response (PR). CONCLUSION: Chemotherapy-induced neutropenia is a predictor of better survival for patients with advanced NSCLC. Prospective randomised trials of early-dose increases guided by chemotherapy-induced toxicities are warranted.

Therapeutic effects of Saireito (TJ-114), a traditional Japanese herbal medicine, on postoperative edema and inflammation after total hip arthroplasty.

Saireito (TJ-114) is a traditional Japanese herbal medicine that has been used for treating edema and inflammation in diseases such as nephritic disease. This study investigates the effect of TJ-114 on postoperative edema and inflammation after total hip arthroplasty (THA). Patients who underwent cementless THA were randomly divided into two groups: Group A consisted of 8 hips of 8 patients who were treated with TJ-114 at a dose of 9 g/day 2 days before surgery and for 2 weeks after surgery; Group B consisted of 9 hips of 9 patients who did not take TJ-114. Although no significant difference was observed between the two groups for lower extremity edema, it was found that swelling of the proximal leg in Group A was less than that in Group B. Furthermore, 3 weeks after surgery, every measuring point in the lower extremity showed that TJ-114 tended to decrease postoperative swelling compared to measurements of swelling of patients who did not take TJ-114. Serum C-reactive protein (CRP) levels of 6 out of 8 patients in Group A decreased and became negative 2 weeks after surgery; however, there were no patients in Group B whose CRP levels became negative after 2 weeks. In conclusion, TJ-114 is safe and useful for the prevention and early recovery of postoperative leg edema after THA with an association of rapid CRP reduction.

Linear IgA bullous dermatosis of neonatal onset: case report and review of the literature.

UNLABELLED: Several small blisters were noticed on the forehead and the trunk of a newborn boy on day 1. The blisters gradually enlarged and spread over the whole body including the oral mucosa. A skin biopsy was performed twice and subepidermal bullae with polymorphonuclear and mononuclear cell infiltration were demonstrated. Direct immunofluorescence showed linear IgA, IgG and C3 depositions along the basement membrane zone and this finding led to a diagnosis of linear IgA bullous dermatosis. So far, internationally, only one case has ever been reported on the disease at neonatal onset. The skin lesions spontaneously regressed and the mucosal lesions were controlled with diaminodiphenylsulfone. CONCLUSION: In neonates with prolonged blistering, autoimmune disease such as linear IgA bullous dermatosis should be considered within the differential diagnosis and an immunofluorescence study must be performed.

Preservation of the bone mineral density of the femur after surface replacement of the hip.

We investigated the effect of the Birmingham hip resurfacing (BHR) arthroplasty on the bone mineral density (BMD) of the femur. A comparative study was carried out on 26 hips in 25 patients. Group A consisted of 13 patients (13 hips) who had undergone resurfacing hip arthroplasty with the BHR system and group B of 12 patients (13 hips) who had had cementless total hip arthroplasty with a proximal circumferential plasma-spray titanium-coated anatomic Ti6A14V stem. Patients were matched for gender, state of disease and age at the time of surgery. The periprosthetic BMD of the femur was measured using dual-energy x-ray absorptiomentry of the Gruen zones at two years in patients in groups A and B. The median values of the BMD in zones 1 and 7 were 99% and 111%, respectively. The post-operative loss of the BMD in the proximal femur was significantly greater in group B than in group A. These findings show that the BHR system preserves the bone stock of the proximal femur after surgery.

Small intestinal metastasis from renal cell carcinoma exhibiting rare findings.

Small intestinal metastasis from renal cell carcinoma (RCC) has only rarely been described. We report two patients who developed small bowel metastases from RCC showing different clinicopathological characteristics. Both patients underwent hemilateral nephrectomy for RCC and developed lung metastases metachronously or simultaneously. One patient developed occlusive ileus caused by multiple polypoid tumours composed of sarcomatoid tissue in the jejunum shortly after nephrectomy. The other patient presented melaena due to bleeding from a Borrmann 2-like tumour in the jejunum six years after nephrectomy. Clinically, his disease was slow-growing. Sarcomatoid histology and Borrmann 2-like tumour in this report are rare findings in metastatic tumour of RCC in the small bowel.

Full weight-bearing after cementless total hip arthroplasty.

In a prospective study of cementless total hip arthroplasty, 19 hips in 17 patients (Group A) were allowed full weight-bearing immediately after the operation while 18 hips in 16 patients (Group B) were first allowed weight-bearing after 6 weeks. Patients were matched for sex, age at surgery, height, weight, and follow-up period and there were no significant differences in hip scores between the two groups. Rehabilitation to gain walking ability with a cane lasted 5.8 days for Group A and 44.8 days for Group B (P = 0.0001). The hospital stay after surgery was 30.1 days for Group A and 46.7 days for Group B (P = 0.006). All patients showed bone ingrowth radiographically. There were no complications in either group.

Gastric cancer with Virchow's and multiple lung metastases showing a remarkable response to preoperative chemotherapy: report of a case.

We report herein a rare case with advanced gastric cancer combined with group 4 lymph node and lung metastases that responded remarkably to neoadjuvant chemotherapy. A 65-year-old man was found to have a well-differentiated type 3 gastric cancer that invaded the duodenum locally and was accompanied with Virchow's, para-aortic lymph nodes, and multiple lung metastases based on physical, endoscopic, and radiological examinations. In addition, his carbohydrate antigen (CA) 19-9 was elevated to 3965U/ml, and CA72-4 to 46U/ml. Prior to surgery, he was treated with 5-fluorouracil (5-FU; 500mg/body per day) and low-dose cisplatinum (CDDP; 10mg/body per day) as neoadjuvant chemotherapy for 6 weeks. As a result, a partial response was obtained in all lesions, and CA19-9 and CA72-4 decreased to 463U/ml and 9.4U/ml, respectively. Four weeks after the completion of neoadjuvant chemotherapy, a distal gastrectomy was performed, and a histopathological examination of the resected specimen showed a grade 2 response to chemotherapy. Immunohistochemically, the thymidylate synthase expression level was very low in the tumor tissues, which might account for the good response to the combination chemotherapy with 5-FU and CDDP observed in the present case.

Renin-producing adrenal tumor: report of a case.

A 19-year-old man with an adrenal tumor associated with hypertension is herein described. The plasma renin activity (PRA) was markedly elevated and the plasma aldosterone level was also increased. The catecholamine level was within the normal range and the glucagone-regitine test was negative. An angiogram revealed the left renal artery to have no stenotic segments, but instead was curved caudally. Magnetic resonance imaging showed a tumor measuring about 8 cm in diameter to be clearly recognized from the left kidney. The blood pressure did not drop when a calcium-channel blocker was used, but was gradually stabilized with the angiotensin converting enzyme (ACE) antagonist. The adrenal tumor was then removed surgically. Normal adrenal tissue was scarcely recognized to the left of the tumor. After surgery, the PRA decreased and blood pressure stabilized rapidly without the ACE antagonist. The possibility of massive renal renin secretion due to suppression by the adrenal tumor was excluded by a method using an antibody to purified human renin.

Role of Na(+)-Ca2+ exchanger in agonist-induced Ca2+ signaling in cultured rat astrocytes.

We have previously demonstrated that activation of the Na(+)-Ca2+ exchanger in the reverse mode causes Ca2+ influx in astrocytes. In addition, we showed that the exchange activity was stimulated by nitric oxide (NO)/cyclic GMP and inhibited by ascorbic acid. The present study demonstrates that the Na(+)-Ca2+ exchanger is involved in agonist-induced Ca2+ signaling in cultured rat astrocytes. The astrocytic intracellular Ca2+ concentration ([Ca2+]i) was increased by L-glutamate, noradrenaline (NA), and ATP, and the increases were all attenuated by the NO generator sodium nitroprusside (SNP). SNP also reduced the ionomycin-induced increase in [Ca2+]i. The NA-induced Ca2+ signal was also attenuated by S-nitroso-L-cysteine and 8-bromo cyclic GMP, whereas it was enhanced by 3,4-dichlorobenzamil, an inhibitor of the Na(+)-Ca2+ exchanger. Treatment of astrocytes with antisense, but not sense, deoxynucleotides to the sequence encoding the Na(+)-Ca2+ exchanger enhanced the ionomycin-induced increase in [Ca2+]i and blocked the effects of SNP and 8-bromo cyclic GMP in reducing the NA-induced Ca2+ signal. Furthermore, the ionomycin-induced Ca2+ signal was enhanced by removal of extracellular Na+ and pretreatment with ascorbic acid. These findings indicate that the Na(+)-Ca2+ exchanger is a target for NO modulation of elevated [Ca2+]i and that the exchanger plays a role in Ca2+ efflux when [Ca2+]i is raised above basal levels in astrocytes.

Three-dimensional display of liver, spleen, hepatoma, and blood vessels by MR imaging and computer graphics.

The technique of generating 3-D images from CT and MR data has made progress. Manipulation of the images has become simpler, the processing time shorter, and the quality better. Clinical application of this technique has been performed for images of brain (5, 7, 8) and bone (1, 2, 6), but only a few studies have been done of abdominal organs (3, 4).

[Research and development of pravastatin].

The attempts to find a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which catalyzes the rate limiting step of cholesterol biosynthesis were started from 1971. The first potent inhibitor, ML-236B (compactin), was found from the culture broth of Penicillium citrinum. Among many derivatives of ML-236B, pravastatin sodium (hereafter refer to pravastatin) was finally selected because of its potency and tissue selectivity. Since pravastatin has a hydroxyl group at 6 beta position in the skeleton of decaline of ML-236B, the microbial hydroxylation was adopted for the production of pravastatin. Streptomyces carbophilus was finally chosen as a potent converter with the formation of a lesser amount of by-products. For the sake of industrial production of pravastatin, many devices and improvements were performed for selecting high potent strains and for culturing conditions both with ML-236B and pravastatin. Pravastatin strongly inhibited the sterol synthesis in freshly isolated rat hepatocytes, but only weakly inhibited in the cells from nonhepatic tissues. This selective inhibition of pravastatin in sterol synthesis was further confirmed by ex vivo and in vivo experiments by using rats and mice. Pravastatin markedly reduced serum cholesterol levels in dogs, monkeys and rabbits, including Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. Pravastatin showed the preventive effect on the development of coronary atherosclerosis and xanthoma in young WHHL rabbits in consequence of maintaining the serum cholesterol levels low. In the clinical trials, pravastatin significantly reduced serum cholesterol and low density lipoprotein cholesterol levels, whereas inversely increased high density lipoprotein cholesterol levels.

Management of congenital diaphragmatic hernia by extracorporeal membrane oxygenation (ECMO).

The purpose of this study was to evaluate the efficacy of extracorporeal membrane oxygenation (ECMO) for patients with congenital diaphragmatic hernia (CDH). Ten patients whose mortality was predicted to be more than 80% with previous therapeutics, were selected to use ECMO over the past five years. Patients were placed on ECMO by cannulating the right jugular vein and the right carotid artery. ECMO was started at 34.3 hours after birth on an average, and the average time on ECMO was 96.3 hours. Seven patients (70%) survived, and six out of them are in good health without any sequelae. In particular, all five patients whose pathological condition needing ECMO was persistent fetal circulation (PFC), survived. Therefore we believe ECMO is highly beneficial to overcome the condition of PFC. The survival rate of CDH patients under 24 hours of age in our hospital is 76.2% (16/21 cases) over the last 5 years, and it has improved compared with 57.1% (12/21 cases) before then. The fact that some of the critical patients who were lethal with conventional management, have been successfully treated by ECMO, played a great role in this improvement.

Fv-1 restriction of endogenous feline C-type RD114 virus genome phenotypically mixed with ecotropic murine leukemia viruses.

Endogenous feline leukemia RD114 virus genome rendered capable of infecting mouse cells by phenotypic mixing with an ecotropic murine leukemia virus (MuLV) exhibited the Fv-1 restriction pattern of the ecotropic murine virus. However, RD114 genomes phenotypically mixed with ecotropic MuLV showed one-hit dose-response kinetics, even when titrated with murine cells with the restricted Fv-1 phenotype.

Mutational analysis of the human immunodeficiency virus vpr open reading frame.

Mutations were introduced by recombinant DNA techniques into the vpr open reading frame of an infectious molecular clone of human immunodeficiency virus type 1. The effect of these changes on the replicative and cytopathologic properties of the virus recovered from transfected cells was studied in several human CD4+ lymphocyte cell lines. In all cases, mutant viruses were infectious and cytopathic. However, when a low-input dose was used, mutants grew significantly more slowly than the wild-type virus. The growth kinetics of vpr mutants were distinct from those of vif and vpu mutants.