Expression of Neurotrophins and Their Receptors Tropomyosin-related kinases (Trk) under Tension-stress during Distraction Osteogenesis

The localization and expression of neurotrophins and their receptors during distraction osteogenesis was investigated in 72 male rat femurs (11 weeks old) to further clarify the concurrence of cellular and molecular events of new bone formation. After osteotomy, a 7-day lag phase was followed by distraction at the rate of 0.25 mm/12 h for 21 days (distraction phase), and a 7-day consolidation phase. The localization of neurotrophins (NGF, BDNF and NT-3) and their receptors tropomyosinrelated kinases (TRKA, TRKB and TRKC) by immunostaining showed positive staining in bone forming cells in each stage, although the presence and staining intensity varied by cell type and phase. The expressions of NGF, BDNF and NT-3 by real-time polymerase chain reaction (real-time PCR) showed that the peak of the mRNA expression of NGF occurred 10 days after distraction. NT-3 increased during bone extension, but decreased when distraction stopped. In contrast, BDNF continued to increase gradually throughout the distraction and consolidation phases. These findings suggest that neurotrophins and their receptors may play different roles in endochondral and intramembranous ossification in distraction osteogenesis. The tension stress caused by distraction may stimulate the expression of neurotrophins and their receptors, and promote osteogenesis

Assessment of Head Wear More Than Ten Years after Total Hip Arthroplasty: 22-mm Zirconia VS. Metal Heads.

The present retrospective study assessed radiographs to determine socket wear in total hip arthroplasty (THA) with 22-mm zirconia or COP (Cobalt-Chrome alloy rich in Cobalt and Phosphorous) heads, and in cemented stems at more than 10 years after operation. Sockets of ultra high molecular weight polyethylene were used in each of two THA groups (13 hips each) in a clinical trial in our hospital between 1989 and 1990. Three observers carried out masked assessments of the radiographs. Upon fi nal examination, there was no remarkable loosening in the zirconia or COP group, and no case had required revision surgery as of 2005. There was a statistically signifi cant diff erence between the 2 groups in average annual linear wear, at 0.093 mm/year and 0.046 mm/year in the zirconia and COP groups, respectively. Volume wear and average annual volume wear were also signifi cantly greater in the zirconia group despite its superior mechanical strength and toughness in vitro. Our present fi ndings do not confi rm early expectations of lower wear in long-term results of 22-mm zirconia femoral heads used in THA

Relationship between intracellular uptake of adriamycin and membrane potential in ADR resistant Ehrlich ascites tumor cells

We observed adiamycin (ADR) uptake and cellular transmembrane potential [amount of intracellular fluorescence of 3,3'- (Di-n-hexyl)- 2,2'- oxacarbocyanine iodide (NK-2280)] in ADR-resistant cells established from Ehrlich ascites tumor cells (EATC) and wild type EATC. In ADR-resistant cells, ADR uptake and the cellular transmembrane potential decreased as the degree of resistance increased. 4,4'- diisothiocyanatostilbene- 2,2'- disulfonic acid (DIDS) induced markedly decreases of ADR uptake and the cellular transmembrane potential. A good correlation was observed between ADR uptake and transmembrane potential in cultured cells

The Minimally Invasive Plate Osteosynthesis (MIPO) Technique with a Locking Compression Plate for Femoral Lengthening

A minimally invasive plate osteosynthesis technique using a locking compression plate (LCP) has been used widely in trauma cases. Its advantages are that the MIPO technique does not interfere with the fracture site and thus provides improved biological healing, and that the LCP has excellent angular stability. Its use in bone lengthening, however, has not been established. In such cases, it is desirable to shorten the external skeletal fixation period as much as possible. Here, the MIPO technique using an LCP was applied to femoral distraction osteogenesis in an attempt to shorten the external skeletal fixation period. For femoral lengthening, the MIPO technique was performed in 2 stages. Orthofix external fixators (Orthofix, England) were used to insert screws from the anterolateral side rather than from the lateral side of the femur for bone lengthening. When sufficient callus formation was detected postoperatively at the site of bone lengthening, and the absence of infection was ensured, limb draping was performed, including a whole external fixator, and then the MIPO technique was applied with an LCP. In 3 cases (5 limbs), the average duration of external skeletal fixation was 134days, the average external-fixation index was 24days/cm, and the average consolidation index was 22days/cm. The MIPO technique using an LCP made it possible to shorten the external skeletal fixation-wearing period in femoral lengthening.</p

Promotion of Bone Regeneration by CCN2 Incorporated into Gelatin Hydrogel

CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique molecule that promotes the entire endochondral ossification process and regeneration of damaged articular cartilage. Also, CCN2 has been shown to enhance the adhesion and migration of bone marrow stromal cells as well as the growth and differentiation of osteoblasts; hence, its utility in bone regeneration has been suggested. Here, we evaluated the effect of CCN2 on the regeneration of an intractable bone defect in a rat model. First, we prepared two recombinant CCN2s of different origins, and the one showing the stronger effect on osteoblasts in vitro was selected for further evaluation, based on the result of an in vitro bioassay. Next, to obtain a sustained effect, the recombinant CCN2 was incorporated into gelatin hydrogel that enabled the gradual release of the factor. Evaluation in vivo indicated that CCN2 continued to be released at least for up to 14 days after its incorporation. Application of the gelatin hydrogel-CCN2 complex, together with a collagen scaffold to the bone defect prepared in a rat femur resulted in remarkable induction of osteoblastic mineralization markers within 2 weeks. Finally, distinct enhancement of bone regeneration was observed 3 weeks after the application of the complex. These results confirm the utility of CCN2 in the regeneration of intractable bone defects in vivo when the factor is incorporated into gelatin hydrogel

Hyperthermotherapy added to the multidisciplinary therapy for penile cancer.

We performed a long-term follow-up of 4 patients with penile cancer who underwent hyperthermotherapy from August 1985 until August 1992. Hyperthermia was applied using a frequency of 350 MHz with a waveguide applicator twice a week for 60 min each for an average of 9.5 times (varying from 6 to 13 times). The total heating time that the temperature of urethra could be kept above 42 degrees C, was 166 min on the average (ranging from 0 to 463 min). Two patients classified as stage I according to the Jackson classification and 1 patient classified as stage IV underwent combined radiotherapy and received an average radiation dose of 53 Gy (range, 40-70 Gy). Among these patients 2 underwent combined chemotherapy with bleomycin or peplomycin. Malignant cells disappeared posttherapeutically and in August 1992, after an average of 5 years and 9 months (varying from 4 years 6 months to 6 years 10 months), the patients were free of recurrences. The one patient on stage IV had extensive invasion of the abdominal wall, but still recovered completely. One patient on stage III underwent combined chemotherapy and hyperthermotherapy, but heating had obviously been insufficient. There was a residue of malignant cells after the treatment and we performed a penectomy. Regarding functional preservation of the penis a multidisciplinary therapy incorporating hyperthermotherapy can be expected to increase the curativity. This indicates that it could induce in an advanced case, where an operation would be difficult, complete remission.</p

Hyperthermotherapy for postoperative local recurrences of rectal cancer.

Between November 1984 and August 1992 we used hyperthermotherapy in six cases of local recurrence of rectal cancer. Hyperthermotherapy was performed on the average 8.7 times (range: 3-18) for each patient for 60 min each. All patients underwent combined radiotherapy and received a mean radiation dose of 42.5 Gy (range: 9-60 Gy). Five patients underwent heating within 1 h after irradiation and one patient simultaneously with the irradiation. Four patients underwent combined chemotherapy and two patients immunotherapy. Before the treatment all patients had painful lesions, but pain decreased posttherapeutically in five patients. Performance status improved in two patients. High carcinoembryonic antigen levels prior to the therapy in four patients decreased in all cases after treatment. Posttherapeutical computed tomograms revealed only minor response or no changes. After the treatment, four patients died of exacerbations of recurrent tumors and one patient of distant metastases. The patient who underwent simultaneous radiohyperthermotherapy is presently alive, in August 1992, 38 months after initiation of the treatment. The 50% survival time after initiation of the treatment was 25 months (range: 10-38 months). Hyperthermotherapy combined with radiotherapy, chemotherapy and/or immunotherapy was useful for the alleviation of pain in patients who developed local recurrence after surgery, and improved survival after recurrences can be expected.</p