Human parathyroid hormone (1-34) increases mass and structure of the cortical shell,with resultant increase in lumbar bone strength,in ovariectomized rats

Estrogen deficiency causes reduction of bone mass and abnormal bone microarchitecture, consequently reducing bone strength. Human parathyroid hormone (hPTH) (1-34) increases bone mass and strength. To clarify the factors that determine the recovery of bone strength in the lumbar vertebrae of ovariectomized rats by intermittent hPTH administration, we analyzed the relationship between skeletal measurements and bone strength. Human PTH (1-34) administration resulted in recovery of cortical bone mineral content (BMC) and cortical bone area to sham the levels, but in resulted in a less pronounced recovery of trabecular BMC and no increase in the total cross-sectional area of the vertebral body. Of the three-dimensional (3D) trabecular bone parameters, hPTH (1-34) increased trabecular thickness (Tb.Th). The cortical shell area of L4, determined by histomorphometry, was also increased. In hPTH-treated rats, the only determinant of the compressive load of L5 was the cortical shell BMC, in the early recovery period (days 42–84). Our data suggest that increased cortical bone mass contributes more than trabecular bone mass and structure to the recovery of bone strength in response to hPTH therapy in the rat lumbar vertebral body after ovariectomy.     

Clinical trial of risedronate in Japanese volunteers: single and multiple oral dose studies

The tolerability and pharmacokinetics of risedronate after a single oral administration and during multiple oral administrations were examined in healthy adult male volunteers. In the single dose study, the dose was increased gradually from 1mg to 2.5, 5, 10, or 20mg. Subsequently, risedronate was given by multiple administration, 5mg per dosing, once daily, for 7 days. The observed adverse events, whose causality was possibly related or unknown, included headache, diarrhea, increased body temperature, increased CK-BB, and increased urinary ₂-microglobulin excretion rate. However, none of these adverse events was clinically significant. The results thus showed that risedronate was well tolerated when delivered as a single administration of up to 20mg or as a multiple administration of up to 5mg/day. In the multiple dose study, changes in urinary deoxypyridinoline suggested the bone antiresorptive activity of risedronate. In the single dose study, AUC and C_max, after the administration of risedronate at 1, 2.5, 5, 10, and 20mg, increased dose dependently, and the T_max, t_1/2, and urinary excretion rates were nearly constant. Therefore, the pharmacokinetic profile of risedronate was considered to show linearity in a dosage range of up to 20mg. Furthermore, the results obtained in the multiple administration study indicated that the plasma concentrations of risedronate reached a steady state on day 4 of administration. The plasma concentrations of risedronate after the administration of 2.5mg risedronate to the Japanese population were nearly comparable to the serum concentrations after the administration of 5mg risedronate to the United Kingdom study population.     

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) levels, as prognostic indicators in NSCLC.

OBJECTIVES: Non-small cell lung cancer (NSCLC) tissue produces numerous growth factors, which are multifunctional and considered predictive of patient survival. This study sought to evaluate the relationship between concentrations of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) in NSCLC tissue and clinicopathological factors, and determine whether these factors correlate with long-term survival. METHODS: We retrospectively investigated 71 patients with histologically confirmed adenocarcinoma or squamous cell carcinoma of the lung, for whom the primary curative approach was surgery, and who received no chemotherapy or radiotherapy prior to surgery. bFGF, VEGF, HGF were measured in extracts prepared from these 71 frozen tissue samples by ELISA. Five- and 10-year survival was obtained to determine the most important predictors of long-term survival. RESULTS: Among clinicopathological parameters, the mean concentration of bFGF was significantly higher in tissue extracts from cases involving metastatic nodal involvement (87.5+/-69.3 ng/100 mg protein) than in those without nodal involvement (57.6+/-42.5 ng; P<0.05). Levels of VEGF in adenocarcinoma (26.8+/-34.0 ng) were higher than for squamous cell carcinoma (12.2+/-13.8 ng; P<0.05). HGF levels also demonstrated histological differences (14.7+/-7.7 vs. 10.6+/-9.7 ng, P<0.05). bFGF protein levels were basically the same, but showed no statistically significant differences with respect to histological type (72.5+/-55.2 vs. 63.6+/-51.5 ng). Patients with high levels of bFGF or VEGF showed significantly worse survival rates than patients with low levels (P=0.0059; P=0.0134). In particular, high concentrations of both bFGF and VEGF correlated with markedly poor prognosis (P<0.0001). Multivariate analysis indicated that lymph node involvement and levels of bFGF and VEGF were independent prognostic factors in cases of NSCLC (adenocarcinoma or squamous cell carcinoma) involving patients who had undergone curative resection. CONCLUSIONS: Adenocarcinoma associated with lung cancer is regarded to have biological characteristics that distinguish it from squamous cell carcinoma. Node invasion may be associated with bFGF. bFGF and VEGF augment each other and are associated with leading to poor prognosis. The results of this study suggests that effective therapy to block angiogenesis may need to address at least both of these factors in cases of NSCLC.     

Laparoscopic resection for gastrointestinal stromal tumors in the stomach

Purpose

Gastrointestinal stromal tumors (GISTs) should be surgically resected, even those smaller than 5?cm in size, which is the threshold of clinical malignancy for submucosal tumors (SMTs) in the gastrointestinal tract. This study reviewed the use of laparoscopic surgery for gastric partial resection of GISTs or SMTs that were suspected to be GISTs.

Methods

Eighteen patients underwent laparoscopic partial resection of the stomach for GISTs or SMTs. The tumor location was confirmed by intraluminal endoscopy. One-half of the circumference around the tumor was dissected, and the tumor was turned toward the abdominal cavity. The nonresected part of the tumor and the edge of the incision line was lifted up using forceps, and the incision line was closed using laparoscopic stapling devices.

Results

Two cases were diagnosed as GIST by endoscopic biopsy. Six patients underwent endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) examinations, which diagnosed five GISTs. There were 18 tumors smaller than 5?cm, including 10 GISTs, 4 leiomyomas, 3 schwannomas, and one heterotopic pancreas.

Conclusions

Endoscopic ultrasound-guided FNAB is recommended for definite preoperative diagnosis of histopathologically unknown SMTs to determine the indications for surgery. The laparoscopic approach with the assistance of endoscopy is useful for improving the curability, with minimal invasiveness for the partial resection of GISTs.     

Effects of Prolonged Tendon Vibration Stimulation on Eccentric and Concentric Maximal Torque and Emgs of the Knee Extensors

The purpose of present study was to compare the effect of Ia afferent attenuation on the activity of alpha motor neuron (MN) during concentric and eccentric action. Eight male subjects were enrolled in the present study. The experiments consisted of two sessions of MVC measurements, since all subjects performed both maximal concentric and eccentric action. EMG signals were simultaneously measured. To establish the baseline of strength, subjects were asked to perform MVC of knee extension in each session. After finishing the measurements, 20 min of vibration stimulation was applied. Immediately after finishing vibration stimulation, the MVC and AEMG were again measured. The means of MVC for concentric knee extension at pre and post- vibration stimulation were 192.2 ± 49.3 Nm and 162.3 ± 47.9 Nm, respectively. The means of MVC for eccentric knee extension at pre and post-vibration stimulation were 299.7 ± 77.0 Nm and 247.3 ± 88. 6 Nm, respectively. Two-factor repeated ANOVA detected significant differences in the MVC. Both main effects for pre-post condition (F(1,7)=, p = 0.0033) and action (F(1,7)=26.35, p = 0.0013) were noted. No interaction effect (action x condition) was noted. The means of AEMG (vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF)) at pre and post -vibration stimulation were decreased. Two-factor repeated ANOVA detected significant differences in AEMG (VM and VL). Both main effects for pre-post condition (VL;F(1,7)=7.27, p = 0.0308, VM; F(1,7)=9.55, p = 0.0175) and action (F(1,7)=12.40, p = 0.0097) were noted in the VL and the VM but not in the RF. Furthermore, significant interaction (action x condition) effect was noted in the VM (F(1,7)=7.03, p = 0.0328) but not in the VL. The MVC and the EMG activity of the VL in response to the prolonged vibration stimulation were significantly reduced in eccentric contraction over concentric contraction. These results represented that a deactivation effect on the alpha MN of the VL during eccentric action was greater than that of concentric action.

Key points

• A deactivation effect on the alpha motor neuron of the vastus lateralis during eccentric action was greater than that of maximal concentric action.

Key words: Concentric contraction, MVC, Vibration stimulation, QF     

Are predictive models for cancer volume clinically useful in localized prostate cancer?

Objectives: To evaluate the correlation between preoperatively predicted and pathologically measured prostate cancer volumes and to investigate the clinical use of preoperatively predicted cancer volume in predicting pathological stage. Methods: Correlations between pathological findings and various preoperative parameters, including the cancer volumes as predicted by using two methods (Vca and estimated PCvol), were analyzed in 196 patients who underwent radical prostatectomy for clinically localized prostate cancer. Results: Pathologically measured prostate cancer volume was significantly correlated with the Vca and estimated PCvol, but the correlation coefficients were respectively only 0.46 and 0.35. Prostate‐specific antigen (PSA), PSA density (PSAD), primary Gleason score, Vca, Vca fraction (Vcafx), and estimated PCvol were significantly higher in 82 patients with extraprostatic cancer than in 114 patients with organ‐confined cancer. Magnetic resonance imaging (MRI) findings were significantly correlated with pathological stage. Multivariate logistic regression analysis indicated that the Vcafx and MRI findings were significant predictors of extraprostatic cancer, but receiver operating characteristic analysis revealed that the combination of Vcafx and MRI findings had no advantage over the combination of Gleason score, PSAD, and MRI findings. Conclusions: Vca and estimated PCvol are significantly correlated with the pathologically measured cancer volume but their ability to accurately predict cancer volume is limited. Vcafx and MRI findings were statistically significant predictors of extraprostatic cancer but their combination was not superior to the combination of Gleason score, PSAD, and MRI findings.     

Current role of liver transplantation for the treatment of urea cycle disorders: a review of the worldwide English literature and 13 cases at Kyoto University.

To address the current role of liver transplantation (LT) for urea cycle disorders (UCDs), we reviewed the worldwide English literature on the outcomes of LT for UCD as well as 13 of our own cases of living donor liver transplantation (LDLT) for UCD. The total number of cases was 51, including our 13 cases. The overall cumulative patient survival rate is presumed to be more than 90% at 5 years. Most of the surviving patients under consideration are currently doing well with satisfactory quality of life. One advantage of LDLT over deceased donor liver transplantation (DDLT) is the opportunity to schedule surgery, which beneficially affects neurological consequences. Auxiliary partial orthotopic liver transplantation (APOLT) is no longer considered significant for the establishment of gene therapies or hepatocyte transplantation but plays a significant role in improving living liver donor safety; this is achieved by reducing the extent of the hepatectomy, which avoids right liver donation. Employing heterozygous carriers of the UCDs as donors in LDLT was generally acceptable. However, male hemizygotes with ornithine transcarbamylase deficiency (OTCD) must be excluded from donor candidacy because of the potential risk of sudden-onset fatal hyperammonemia. Given this possibility as well as the necessity of identifying heterozygotes for other disorders, enzymatic and/or genetic assays of the liver tissues in cases of UCDs are essential to elucidate the impact of using heterozygous carrier donors on the risk or safety of LDLT donor-recipient pairs. In conclusion, LT should be considered to be the definitive treatment for UCDs at this stage, although some issues remain unresolved.     

Living donor liver transplantation for biliary atresia complicated by situs inversus: technical highlights.

Living-donor liver transplantation (LDLT) has become an established technique to treat children with end-stage liver disease. Biliary atresia (BA), one of the most common indications for liver transplantation in children, can be associated with situs inversus (SI). In the past, the presence of SI has been considered to be an absolute contraindication for liver transplantation because of the technical difficulties. Recently, some reports of successful diseased-donor liver transplantation in patients with BA complicated by SI have been published; however, few reports of that with LDLT exist. The technical difficulties involved with LDLT for such cases have not been described. Herein, we present 4 successful cases of LDLT for BA with SI. Complex anomalies associated with SI, such as a hepatic artery arising from the supraceliac aorta, a preduodenal portal vein, and absence of the retrohepatic inferior vena cava, increase the technical difficulties involved with the operation. Additional caution is required in LDLT because a living-donor graft has short vessels and the availability of vascular grafts from the donor is limited. In conclusion, LDLT for BA complicated by SI can be managed successfully with technical modifications and scrupulous attention. This series represents the largest reported group of patients with BA complicated by SI who underwent a successful LDLT procedure.     

Living-Donor Liver Transplantation for Hepatoblastoma

Hepatoblastoma is the most common malignant liver tumor in children. Recently, liver transplantation has been indicated for unresectable hepatoblastoma. We retrospectively reviewed 14 children with a diagnosis of hepatoblastoma who had undergone living-donor liver transplantation (LDLT) at Kyoto University Hospital. During the period from June 1990 to December 2004, 607 children underwent LDLT. Of these interventions, 2.3% were performed for hepatoblastoma. Based on radiological findings, the pre-treatment extent of disease (PRETEXT) grouping was used for pre-treatment staging of the tumor. There were grade III in seven patients and grade IV in seven patients. Thirteen patients received chemotherapy, and seven underwent hepatectomy 11 times. Immunosuppressive treatment consisted of tacrolimus monotherapy in 11 patients. Actuarial 1- and 5-year graft and patient survival rates were 78.6% and 65.5%. The poor prognostic factors were macroscopic venous invasion and extrahepatic involvement with 1-year and 5-year survival rates of 33.0% and 0%. Pediatric patients without these factors showed an acceptable 5-year survival rate of 90.9%. LDLT provides a valuable alternative with excellent results in children with hepatoblastoma because it allows optimal timing of the liver transplantation, given the absence of delay between the completion of chemotherapy and planned liver transplantation.     

Eye-pursuit and reafferent head movement signals carried by pursuit neurons in the caudal part of the frontal eye fields during head-free pursuit

Eye and head movements are coordinated during head-free pursuit. To examine whether pursuit neurons in frontal eye fields (FEF) carry gaze-pursuit commands that drive both eye-pursuit and head-pursuit, monkeys whose heads were free to rotate about a vertical axis were trained to pursue a juice feeder with their head and a target with their eyes. Initially the feeder and target moved synchronously with the same visual angle. FEF neurons responding to this gaze-pursuit were tested for eye-pursuit of target motion while the feeder was stationary and for head-pursuit while the target was stationary. The majority of pursuit neurons exhibited modulation during head-pursuit, but their preferred directions during eye-pursuit and head-pursuit were different. Although peak modulation occurred during head movements, the onset of discharge usually was not aligned with the head movement onset. The minority of neurons whose discharge onset was so aligned discharged after the head movement onset. These results do not support the idea that the head-pursuit-related modulation reflects head-pursuit commands. Furthermore, modulation similar to that during head-pursuit was obtained by passive head rotation on stationary trunk. Our results suggest that FEF pursuit neurons issue gaze or eye movement commands during gaze-pursuit and that the head-pursuit-related modulation primarily reflects reafferent signals resulting from head movements.