Tissue engineering models of human digits: effect of periosteum on growth plate cartilage development

Tissue-engineered middle phalanx constructs of human digits were investigated to determine whether periosteum wrapped partly about model midshafts mediated cartilage growth plate formation. Models were fabricated by suturing ends of polymer midshafts in a human middle phalanx shape with polymer sheets seeded with heterogeneous chondrocyte populations from bovine articular cartilage. Half of each midshaft length was wrapped with bovine periosteum. Constructs were cultured, implanted in nude mice for up to 20 weeks, harvested and treated histologically to assess morphology and cartilage proteoglycans. After 20 weeks of implantation, chondrocyte-seeded sheets adjacent to periosteum-wrapped midshaft halves established cartilage growth plates resembling normal tissue in vivo. Sheets adjacent to midshafts without periosteum had disorganized cells and no plate formation. Proteoglycans were present at both midshaft ends. Periosteum appears to guide chondrocytes toward growth plate cartilage organization and tissue engineering provides means for carefully examining construct development of this tissue.     

Complications in the central nervous system during chemotherapy for childhood acute lymphoblastic leukemia: JACLS ALL-02 study

We evaluated central nervous system (CNS) complications treated under the ALL-02 protocol of the Japan Association of Childhood Leukemia Study (JACLS) from April 2002 to March 2005. According to NCI Toxicity Criteria, 17 events of grade 3 and 4 CNS complications were reported in 15 out of 541 patients. Out of these CNS complications, leukoencephalopathy was seen in 5 patients; seizure in 5; cerebrovascular disease in 3; conscious disturbance in 2; and hypertensive encephalopathy and reversible posterior leukoencephalopathy syndrome in one patient each. The complications were intensively observed during induction therapy and the last of the early phase chemotherapy. The protocol treatment was stopped or modified in most patients after CNS complications. MRI imaging demonstrated no improvement in one patient with leukoencephalopathy who developed an isolated CNS relapse, while other patients were alive and remain in their first complete remission without any neurological sequelae. Further studies will be required to analyze risk factors for CNS complications during chemotherapy not accompanied by irradiation and to establish alternative treatments after the appearance of such CNS complications.     

Relation between comprehensive-geriatric assessment and the ability of self-administration in elderly diabetic patients

Intellectual ability of self-administration plays a crucial role in a diabetes regimen. However, in many cases, self-administration is considered difficult, because of the impairment of activities of the individual's daily living (ADL), instrumental ADL and cognitive function. To assess comprehensive-geriatric-assessment (CGA) in elderly diabetic sufferers, 62 elderly inpatients and outpatients aged over 70 years were investigated. CGA includes Barthel index (BI), Mini-mental-state-examination (MMSE) and the Tokyo Metropolitan Institute of Gerontology index of competence (TMIGIC). The relation of ability to self-administer and CGA was examined. In oral therapy, there was significant difference between self-administration and non-self-administration in MMSE (p=0.0065), BI (p=0.0219) and TMIGIC (p=0.0053). Among these indexes, TMIGIC was the most sensitive index in oral therapy. In insulin therapy, there was also significant difference between self-administration and non-self-administration: MMSE (p=0.00042), BI (p=0.000019) and TMIGIC (p=0.0019). Among these indexes, BI was the most sensitive index in insulin therapy. It was suggested that CGA was useful to assess the ability of self-administration in elderly diabetic patients.     

IN.PACT AV access randomized trial: Japan cohort outcomes through 12 months

Purpose

There is a lack of adjudicated and prospectively randomized published outcomes on the use of drug-coated balloons (DCB) to treat dysfunctional arteriovenous fistula in Asian patients. This post hoc subgroup analysis of 112 Japanese participants from the global IN.PACT AV Access trial reports outcomes through 12 months.

Materials and Methods

Participants were treated with DCB (n = 58) or standard non-coated percutaneous transluminal angioplasty (PTA) balloons (n = 54). Outcomes included target lesion primary patency (TLPP), access circuit primary patency, and safety.

Results

Through 6 months, TLPP was 86.0% (49/57) in the DCB group and 49.1% (26/53) in the PTA group (p < 0.001). Through 12 months, TLPP was 67.3% (37/55) in the DCB group and 43.4% (23/53) in the PTA group (p = 0.013).

Conclusion

In this post hoc analysis of Japanese participants from the IN.PACT AV Access trial, participants treated with DCB had higher TLPP through 6 and 12 months compared with PTA.     

In Vitro-In Vivo Correlation of Blood–Brain Barrier Permeability of Drugs: A Feasibility Study Towards Development of Prediction Methods for Brain Drug Concentration in Humans

Pharmaceutical Research - In vitro human blood–brain barrier (BBB) models in combination with central nervous system-physiologically based pharmacokinetic (CNS-PBPK) modeling, hereafter...     

A case of acral lentginous melanoma: the correlation between CD95L expression on melanoma cells and apoptosis of tumor infiltrating lymphocytes

There is an increasing amount of evidence that melanoma cells express the ligand for CD95 (CD95L), a potent inducer of apoptosis which contributes to creating the immune privileged circumstances of tumor sites. However, it still remains to be demonstrated whether the capacity of melanoma cells to express CD95L is acquired during the progression. We addressed this question with a case of acral lentiginous melanoma by employing immunostaining using an antibody directed against CD95L as well as by in situ TUNEL staining. H&E-staining of tumor specimens revealed that there were two different growth patterns. The central part of the tumor showed a deeper invasion into the dermis (Breslow thickness >4 -mm). The horizontally growing edge of the tumor proliferated more superficially (Breslow thickness<3-mm). Relatively fewer lymphocytes were observed around the melanoma nests in central areas, which expressed detectable amounts of CD95L. In contrast, more lymphocytes were observed among the melanoma cells in the peripheral lesion, where CD95L was not detected. To evaluate the relevance of the CD95L expression, in situ TUNEL staining was performed. This indicated a significant correlation of lymphocyte apoptosis with CD95L expression on melanoma cells. Together the data suggest that expression of CD95L is turned on depending on the level of melanoma, and that it may tribute to creating immune privileged circumstances by initiating apoptosis of tumor filrating lymphocytes.