Behavioral and electrophysiological correlates of human mesencephalic dopaminergic xenograft function in the rat striatum

While human fetal xenografts placed into immunocompromised animal hosts have been shown to survive and grow, their ability to function and influence the host tissue has not been fully examined. Therefore, we implanted grafts of human fetal mesencephalic tissue intracranially into rats with unilateral 6-hydroxydopamine lesions of their nigrostriatal dopaminergic innervation and tested the rats behaviorally for reductions in apomorphine-induced rotations. The purpose of this study was to test the ability of these grafts to provide a functional reinnervation by comparing the behavioral changes with the morphology and presence of electrophysiologically active dopaminergic neurons within the graft and with firing rates of host striatal neurons. Adult Sprague-Dawley rats that had been unilaterally lesioned and that showed a stable two peak pattern of apomorphine-induced rotations received grafts of human fetal mesencephalic tissue placed directly into the lesioned striatum. These rats were then further tested each month for five months for reductions in their turning behavior. At 5 to 6 months postgrafting, electrophysiological recordings were made of cells within the graft and within the host striatum. The rats were then examined immunohistochemically to evaluate graft survival and extent of reinnervation of the host tissue. The rats receiving mesencephalic dopaminergic grafts demonstrated a 79% reduction in their apomorphine-induced rotations. Electrophysiological recordings revealed spontaneously active dopaminergic neurons within the graft as well as host striatal cell firing rates consistent with those of dopamine-innervated cells. Furthermore, immunohistochemical studies confirmed graft survival and revealed marked fiber outgrowth from the graft into and throughout the striatum. Taken together these findings provide evidence that grafts of human fetal mesencephalic tissue are able to produce behavioral improvements in lesioned animals which are associated with the presence of dopaminergic neurons within the graft and are consistent with normal host striatal cell activity levels.     

Mental health in young people in relation to child welfare and institutional care in childhood

This study shows that children with experience of child welfare and institutional care are clearly more disturbed than their peers who lived without external intervention and with their original families. The results indicate that child welfare intervention has only been of limited help to disadvantaged children especially for children with psychiatric and educational problems. Preventive measures have to be extended and psychotherapeutic interventions intensified before child welfare can compensate the handicaps and drawbacks of seriously disadvantaged children and secure the quality of life for them.     

Treatment of multiple myeloma in old patients

Patients aged 70 yr or older with multiple myeloma were treated, when suitable, according to concurrent trial protocols for younger patients, with the exception that the cytostatic regimen was not allocated at random. Intermittent melphalan and prednisone (MP) was given as the primary treatment to 42 patients and 5-drug combination MOCCA to 68 patients. The groups were comparable with each other, and the distribution of the clinical stages of the patients was similar to the younger patients in concurrent trials. An at least 50% response was achieved in 33% (SE 7.3) with MP and in 75% (SE 5.3) with MOCCA. The median survival times were 39 and 32 months, the relative age-adjusted survival times 45 and 41 months, respectively. Advanced age as such is thus no contraindication for active treatment of myeloma, and in suitable patients the results compare well with those achieved in younger patients.     

Human ankle cartilage deformation after different in vivo impact conditions

Recently, the general finding of increased ankle cartilage stiffness to loading has been challenged, suggesting the need for the investigation of different in vivo loading conditions. Therefore, the objectives of the present study were to determine ankle (talar) cartilage deformation after in vivo loading using 3D volume change calculation and to establish any difference in volume change between four weight-bearing exercises. The four exercises represented increasing impact (bilateral knee bends <unilateral knee bends <drop jumps) as well as two types of loading: dynamic and static loading (i.e. unilateral knee bends and unilateral static stance). Based on MRI, 3D reconstructions of talar cartilage were generated to determine 3D volumes before and after four exercises in 13 healthy subjects (bilateral and unilateral knee bends, static unilateral stance, drop jumps). Mean talar deformation (volume decrease) was 8.3% after bilateral knee bends (P = 0.001), 7.7% after unilateral knee bends (P = 0.020), 14.6% after unilateral static stance (P < 0.001), 12.5% after drop jumps (P = 0.001). Statistical analysis also revealed deformation to be significantly higher after unilateral static stance than after unilateral knee bends (P = 0.017). These results suggest that talar cartilage endures substantial deformation during in vivo loading characterized by more deformation (i.e. higher volume change) after static than after dynamic loading.     

Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women

OBJECTIVE: The recovery of bone mineral density (BMD) after surgical cure of primary hyperparathyroidism (PHPT) seems to be multifactorial and not just dependent on declining PTH. The aim of the present study was to evaluate the role of sex steroids in this context. DESIGN AND PATIENTS: Thirty-six postmenopausal women with PHPT were examined before and 1 year after curative parathyroidectomy. Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83). BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry. No patient received any replacement therapy with sex hormones or treatment with corticosteroids, oestrogen receptor modulators or bisphosphonates. MEASUREMENTS: Serum concentrations of oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, SHBG, PTH and calcium. RESULTS: Postoperative increase of free (bioavailable) testosterone was positively correlated to the change of BMD in the hip (P < 0.01), whereas the change of PTH in serum correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple regression analysis showed that bioavailable testosterone was the most important determinant of change in BMD in both spine and hip (femoral neck: P < 0.05; Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The increase of bioavailable testosterone after curative parathyroidectomy was related to declining SHBG. CONCLUSIONS: An increase of bioavailable testosterone following surgical cure of PHPT is related to improvement of hip and lumbar spine BMD in postmenopausal women. This previously unknown hormonal interaction may also be important to other aspects of hyperparathyroidism.     

Participation profiles in domestic life and peer relations as experienced by adolescents with and without impairments and long-term health conditions

Purpose: To investigate how individual and environmental factors relate to self-reported participation profiles in adolescents with and without impairments or long-term health conditions. Methods: A person-oriented approach (hierarchical cluster analysis) was used to identify cluster groups of individuals sharing participation patterns in the outcome variables frequency perceived importance in domestic life and peer relations. Cluster groups were compared using one-way analysis of variance (ANOVA). Results: A nine-cluster solution was chosen. All clusters included adolescents with impairment and long-term health conditions. Perceived importance of peer relations was more important than frequent attendance in domestic-life activities. Frequency of participation in dialogues and family interaction patterns seemed to affect the participation profiles more than factors related to body functions. Conclusion: Type of impairment or long-term health condition is a weaker determinant of membership in clusters depicting frequency and perceived importance in domestic life or peer relations than dialogue and family environment.