Pharmacokinetics and disposition of recombinant human osteoprotegerin (rhOPG) after intravenous administration in female fischer rats.

1. Osteoprotegerin (OPG) is a secreted member of the tumour necrosis factor receptor (TNFR) family that leads to the suppression of the differentiation, activation and survival of osteoclasts. The objective was to investigate the in vivo pharmacokinetics and tissue distribution of full-length recombinant human OPG (rhOPG) as well as its clearance mechanism using (125)I-labelled protein ((125)I-rhOPG) after intravenous administration to female Fischer rats. 2. (125)I-rhOPG was rapidly and predominantly distributed to the liver after dosing (3 mg kg(-1)). Immunohistochemical analysis indicated that rhOPG was located in the sinusoids of the liver. 3. The hepatic uptake of (125)I-rhOPG (0.01 mg kg(-1)) was partly regulated under a saturable process. Pre-dosing of some sulfated glycans (20 mg kg(-1)), especially dextran sulfate, heparin and fucoidan, markedly inhibited the hepatic uptake of (125)I-rhOPG. The clearance of (125)I-rhOPG was markedly reduced by the conjugation of dextran sulfate. 4. The results suggested that the hepatic clearance of (125)I-rhOPG was mainly mediated by the interaction with glycosaminoglycans.

Frequent reduced expression of alpha-1B-adrenergic receptor caused by aberrant promoter methylation in gastric cancers.

Recent studies have suggested that epigenetic inactivation of tumour-related genes by promoter methylation participates in the development of gastric cancer. We newly identified the frequently aberrant promoter methylation of alpha-1B-adrenergic receptor (ADRA1B) in colorectal cancer by methylation-sensitive representational difference analysis (MS-RDA) and examined the methylation status of the ADRA1B promoter in 34 paired samples of colorectal cancer and surrounding epithelial tissue, and 34 paired samples of gastric cancer and surrounding epithelial tissue. In colorectal cancers, only four of 34 (11.8%) tumours showed ADRA1B promoter methylation. In contrast, ADRA1B promoter methylation was detected in 24 of 34 (70.6%) gastric cancers and in 14 of 34 (41.2%) surrounding epithelial tissues. The frequency of ADRA1B promoter methylation was higher in gastric epithelial tissues with intestinal metaplasia (41.6%) than in those without intestinal metaplasia (25.0%). Reverse transcription-PCR detected reduced ADRA1B expression in 12 of 18 (66.7%) gastric cancers, and its promoter methylation was detected in 11 of these 12 (91.7%) gastric cancers with reduced ADRA1B expression. Thus, ADRA1B promoter is frequently methylated in gastric cancer. Our results suggest that the ADRA1B gene is an important tumour-related gene frequently involved in the development and progression of gastric cancer.

Chromosomal numerical aberrations of exfoliated cells in the urine detected by fluorescence in situ hybridization: clinical implication for the detection of bladder cancer.

Numerical aberrations of chromosomes 7 and 9 of exfoliated cells from the urinary tract were examined using fluorescence in situ hybridization (FISH). To minimize contamination with inflammatory, squamous and normal transitional cells all samples were stained using Giemsa's solution and clusters of transitional cells were selected for FISH analysis. Samples collected from 21 patients who had cystoscopic monitoring for bladder cancer were used in this study. Cystoscopy was positive in seven patients and five biopsy-proven transitional cell carcinomas were identified. Among the patients with cancer recurrence, numerical chromosomal aberrations were detected in four cases (sensitivity: 80%) and positive cytology in two cases. This preliminary pilot study shows FISH can be a useful tool for the detection of recurrence during a follow up of bladder cancer.

Arthroscopic management of temporomandibular closed lock.

Sixty-three consecutive patients with painful closed lock involving 83 temporomandibular joints were treated by surgery and followed up for at least 24 months. Prior to surgical treatment all had imaging to demonstrate that the cause of their painful jaw locking was an anterior displaced disc without reduction. All patients had received at least three months non-surgical treatment without response. The arthroscopic surgery consisted of release of adhesions, manipulation and placement of 25 mg hyaluronic acid into the joint space. No significant surgical complications occurred. Postoperative treatment involved physical therapy and stabilization splints. At 24 months after surgery 57 patients (90.5 per cent) had no pain and month opening had improved from preoperative 27.2 +/- 5.4 mm to 44.4 +/- 4.1 mm (p < 0.001). This study shows that arthroscopic surgery with continuing non-surgical therapy is a highly effective treatment for painful closed lock.

Absorption of epirubicin instilled intravesically immediately after transurethral resection of superficial bladder cancer.

As postoperative adjuvant therapy for superficial bladder cancer, intravesical instillation therapy is commonly conducted. In this case, from the view point of prevention of intraoperative dissemination, commencement of instillation therapy at an early postoperative period is preferred. However, increased drug permeability is suspected because of damage to the bladder mucosa during operation. Therefore, this study was conducted to investigate the plasma level of epirubicin (EPI) instilled immediately after transurethral operation. EPI (20 mg/40 ml or 50 mg/100 ml) was instilled immediately after a transurethral operation, and retained in the bladder for 1 h. Blood samples were obtained before instillation, as well as 30, 60, 120 and 240 min after instillation, and EPI levels were assayed. The mean EPI concentrations (ng/ml) among the 20-mg/40 ml group (n = 5) were < 2.5 and < 2.0 at 30 and 60 min, respectively, after which they were undetectable. The 50-mg/100 ml group (n = 5) recorded 5.0, 4.4 and < 3.0 after 30, 60 and 120 min, respectively, and after 240 min it was undetectable. Intravesical instillation of EPI immediately after a transurethral operation causes a small increase in the plasma level and it is thought to cause small systemic side effects.

Peripheral facial palsy after sagittal split ramus osteotomy for setback of the mandible. A case report.

The case of a 21-year-old man who underwent sagittal split setback osteotomy is described. He experienced facial nerve palsy 2 days after his surgery. However, after physical therapy and the administration of vitamins, he regained normal function within 3 months. The literature related to postoperative facial nerve paralysis is briefly reviewed.

[Measurement of serum tissue polypeptide antigen (TPA) in patients with malignant tumor using prolifigen TPA-M "Daiichi" kit].

Serum tissue polypeptide antigen (TPA) was measured using a newly developed Prolifigen TPA-M "Daiichi" kit in 1,236 healthy subjects, 2,867 patients with malignant tumors, and 901 with benign diseases. Because 94.0% of healthy subjects had serum TPA under 70 U/l, the cut-off value was set at 70 U/l. Serum TPA was elevated in more than 50% of patients with head and neck cancer, lung cancer, liver cancer, gallbladder or bile duct cancer, pancreatic cancer, colorectal cancer, ovarian cancer, and prostate cancer. The overall positive rate in malignant tumors was 55.5%. Serum TPA was higher in advanced cancer than in earlier stage cancer, and decreased after the resection of the tumor. The false positive rate in benign diseases was 31.3%. ROC analysis revealed the usefulness of TPA as a tumor marker in many cancers. The correlation coefficient between TPA and CYFRA 21-1, and between TPA and TPSA, was 0.747 and 0.694, respectively. In conclusion, measurement of serum TPA using the new kit is useful in the management of patients with various malignant tumors.

Giant neurinoma occupying the holocervical and upper thoracic regions: case report.

We report a case with a giant spinal neurinoma located between the foramen magnum and fifth thoracic levels. The patient did not develop any neurologic symptoms until 16 years after the onset of hydrocephalus. The latter, successfully treated with a ventriculoperitoneal shunt, was associated with a cerebrospinal fluid protein of 400 mg/dL and was in all probability the first sign of the spinal cord tumor.

Endoscopic observation of the syrinx in Chiari malformation--case report.

The cervical syrinx cavity in a 27-year-old male with Chiari 1 malformation was inspected with a flexible small-caliber endoscope during syringo-subarachnoid shunting. A cleft was observed in the midline on the ventral wall of the cavity, from which blood vessels emerged and ran along the wall. Several strands accompanying the blood vessels passed from one wall to another. The endoscope was also used to evaluate whether any obstacles to the passage of a shunt tube were present in the subarachnoid space. Endoscopic observation of the syrinx cavity is helpful in performing the shunt operation.

[An intradural arachnoid cyst of the craniovertebral junction; a case report].

An intradural arachnoid cyst of the craniovertebral junction possibly of traumatic origin is reported. A 59-year-old man was admitted to our hospital with a 10-month history of progressive gait disturbance. He had a history of head injury with a fracture of the occipital bone. Myelography revealed pooling of the contrast medium in the posterior fossa and on the dorsal sides of C1 and C2. Metrizamide-enhanced computed tomography also showed pooling at the same level. Magnetic resonance imaging indicated a large cystic lesion at the craniovertebral junction. Craniectomy of the posterior fossa and laminectomy of C1, C2 and C3 were performed, and an intradural cyst with thickened dura and arachnoid was found. The cyst wall was opened to communicate with the subarachnoid space. Histological findings of the specimen showed that the arachnoid was thickened. There are over 130 reports of intradural arachnoid cyst of the spine, but those of traumatic origin are rare, and cysts located in the intracranial to spinal region are extremely rare.

The system and procedures of percutaneous intradiscal laser nucleotomy.

Since 1986, percutaneous intradiscal laser nucleotomy (PILN) has been studied in the authors' laser laboratory. The purpose of this report is to develop PILN as an alternative to chemonucleolysis and percutaneous discectomy, which are currently applied, and to establish a safe, easy, accurate and short-time therapy method for lumbar disc herniation. After laser irradiation, intradiscal pressures (IDP) decreased and the nucleus pulposus was gradually replaced with cartilaginous fibrous tissue. The evaluation of heat distribution with thermocouples and thermography was done to determine safe optimum irradiating conditions and to develop a new double-lumen needle and a bare quartz fiber. Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser devices have been improved for easy and safe use, and a new tip type pressure transducer has been made for improved therapeutic results using this new method.