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Study design:Controlled, repeat-measures study.Objectives:To determine if functional electrical stimulation (FES) can affect bone atrophy in early spinal cord injury (SCI), and the safety, tolerance and feasibility of this modality in bone loss remediation.Setting:Spinal Injuries Units, Royal Adelaide Hospital and Hampstead Rehabilitation Centre, South Australia.Methods:Patients with acute SCI (ASIA A–D) were allocated to FES (n=23, 28±9 years, C4–T10, 13 Tetra) and control groups (CON, n=10, 31±11 years, C5–T12, four Tetra). The intervention group received discontinuous FES to lower limb muscles (15 min sessions to each leg twice daily, over a 5-day week, for 5 months). Dual energy X-ray absorptiometry (DEXA) measured total body bone mineral density (tbBMD), hip, spine BMD and fat mass (FM) within 3 weeks, and 3 and 6 months postinjury.Results:FES and CON groups' tbBMD differed significantly at 3 months postinjury (P<0.01), but not thereafter. Other DEXA measures (hip, spine BMD, FM) did not differ between groups at any time. No adverse events were identified.Conclusion:Electrically stimulated muscle activation was elicited, and tetanic effects were reproducible; however, there were no convincing trends to suggest that FES can play a clinically relevant role in osteoporosis prevention (or subsequent fracture risk) in the recently injured patient. The lack of an osteogenic response in paralysed extremities to electrically evoked exercise during subacute and rehabilitation/recovery phases cannot be fully explained, and may warrant further evaluation.Spinal Cord (2007) 45, 78–85. doi:10.1038/sj.sc.3101929; published online 25 April 2006 [ABSTRACT FROM AUTHOR]

Purpose: Describe clinical practice, inter-disciplinary clinical pathway and core principles of care within a mild traumatic brain injury (mTBI) rehabilitation team., Methods: An observational study examined inter-disciplinary practice, nested within an observational trial investigating team-based mTBI rehabilitation. Data were collected to describe clinical service over 12 months. Activity data quantified clinical sessions per participant, mode of service delivery and content of sessions using custom-designed codes. The clinical team gathered narrative data to confirm the inter-disciplinary clinical pathway and individual discipline practice., Results: 168 participants entered the rehabilitation program during the 12 months. A single Allied Health Screening Assessment identified patient priorities. Occupational Therapy (OT) and Physiotherapy (PT) provided the majority of clinical sessions; the team also comprised Social Work, Rehabilitation Medicine, Speech Pathology and Clinical Psychology. Telehealth was the most common service delivery mode (54%). Median session numbers per participant ranged 1-4 for all disciplines; mean/maximum occasions of service were highest for PT (6.9/44) and OT (6.8/39)., Conclusion: A small proportion of participants received much higher number of sessions, consistent with intractable issues after mTBI. High attendance rates indicate the predominantly telehealth-delivered model was feasible. The clinical approach included early prioritizing of discipline input and follow-up after discharge.

Objectives: To identify the prevalence and risk factors in the development of Neurogenic Heterotopic Ossification (NHO) in traumatic brain and spinal cord injured patients admitted to specialised units., Methods: An audit protocol was used to gather all clinically relevant data, in specific patient groups, relating to the prevalence of NHO, and was statistically analysed to identify traumatic brain injury (TBI) and traumatic spinal cord injury (TSCI) patients at high risk of developing NHO., Results: 262 TBI and 151 TSCI patients were identified. NHO was diagnosed in 10 and 16 patients with TBI and TSCI, respectively; 18 clinically relevant characteristics were analysed for association with NHO in these patient groups. The only common variables associated with NHO in both neurological conditions were deep vein thrombosis and/or pulmonary emboli (DVT/PE)., Conclusions: The prevalence of NHO in TBI patients is less than one-third of that found in TSCI patients, ~4% and 11%, respectively. This study also suggests that the risk factors associated with NHO in TBI patients are distinct from those identified as risk factors in TSCI patients.

A series of cultured cell lines (designated UCRU-BL-13) has been established from different serial passages of a multiply aneuploid human bladder transitional-cell carcinoma xenografted in nude mice. Serial passage of the xenografts in vivo and of the cell lines in vitro was accompanied by shifts in the tumor ploidy, with dominance of different major peaks. Despite this, the expression of tumor markers remained constant, and consistent chromosomal markers were observed both in the 8th xenograft passage and in a subline in tissue culture established over a year apart. Chromosomal numbers reflected the predominant aneuploid peaks observed; consistent numerical and structural changes included a marker derived from chromosome 1, 8p-, -10, 11q+, and 17q+. The cell line derived from the initial xenograft comprised a mixture of transitional, adenocarcinoma and squamous carcinoma cells in early passage, but adenocarcinoma cells were absent from later passages. The lines expressed the B-blood-group antigen, histocompatibility antigens, receptors for transferrin and EGF, and reacted with a series of monoclonal antibodies (MAbs) directed to malignant human epithelial cell lines. These lines provide a model for studying the evolution of tumor heterogeneity and drug resistance in bladder carcinoma exhibiting multiple aneuploidy.

The xenograft line, UCRU-PR-2, has been characterized further. Established from a primary human undifferentiated small cell carcinoma of the prostate, it has been maintained as a stable xenograft line in nude mice and is currently in passage 9. The tumor has maintained the features of small cell undifferentiated carcinoma but shows epithelial as well as neuroendocrine characteristics. In this paper, we describe synthesis and secretion of peptide hormones, ACTH, beta-endorphin and somatostatin in vivo and ACTH and beta-endorphin in vitro by the tumor, UCRU-PR-2. This suggests that the gene for proopiomelanocortin is expressed and that processing of the molecule occurs. This line may yield insights into the histogenesis of the subtypes of prostate cancer, and also aid studies of regulation of ectopic hormone production.

Twenty bladder biopsies from patients with primary transitional cell carcinoma were inoculated into nude mice. To date, eleven of these have grown as primary implants and three serially transplantable xenograft lines (UCRU-BL-12, UCRU-BL-13, UCRU-BL-14) have been established. The histological and ultrastructural features of human transitional cell carcinoma have been maintained in each line. Despite a relatively uniform histological appearance, several indices of occult tumor heterogeneity have been revealed. Immunocytochemical staining was negative for beta-subunit human chorionic gonadotrophin but positive for carcinoembryonic antigen only in areas of squamous differentiation. All three tumors bound peanut lectin. Flow cytometric DNA analysis of UCRU-BL-13 showed multiple aneuploid peaks, separate populations being demonstrated in different xenografts of the same generation. However, the morphologies of these tumors remained identical. On initial implantation UCRU-BL-12 and UCRU-BL-14 were near diploid but aneuploid populations became apparent with increasing passage number. Each xenograft line caused cachexia in the host mice. Treatment with the cisplatin analogue, isopropyl platinum, ameliorated the cachexia displayed by mice carrying UCRU-BL-14 but did not cause tumor regression. UCRU-BL-12, when tested with cisplatin, isopropyl platinum, and carboplatin, showed equivalent growth retardation with each drug. These xenografted human bladder cancers may be useful models for the study of heterogeneity of the tumor populations in bladder cancer and for the evaluation of new approaches to treatment.

Tumour-cell heterogeneity has been studied in a continuous cell line, UCRU-BL-17CL, established from a xenografted human primary bladder carcinoma. The cell line, grown in vitro for more than 30 generations, reflects the pathology of both the xenograft from which it was derived and the original human tumour. It comprises mainly adenocarcinoma cells which secrete mucin in vitro, as well as squamous and transitional carcinoma cells. Features of both adenocarcinomatous and squamous differentiation have been observed within the same cell. The line expresses ABH blood group isoantigens, binds to peanut lectin and reacts with monoclonal antibodies (MAbs) raised against keratin and against normal and malignant epithelial cells. It also reacts with MAbs against ras p21 proteins and the epidermal growth factor receptor (EGFR). It shows high levels of lactic acid dehydrogenase isozyme 5, consistent with a high-grade tumour, forms colonies in methylcellulose and is tumorigenic in nude mice. The karyotype (human) shows many marker chromosomes, consistent with expression of EGF receptors and ras p21 proteins, and an 11:13 translocation. DNA content, as studied by flow cytometry, reveals a shift from tetraploid to near triploid. This line may provide a useful model for studies of the histogenesis of bladder cancer and the relationship between transitional-cell carcinoma and the other histological subtypes of this disease.

A human small cell undifferentiated carcinoma of the prostate, xenografted in nude mice, was analyzed both cytogenetically and by DNA flow cytometry. The DNA content of the line indicated its stability on serial passage, and was consistent with the cytogenetic findings. The banded karyotype was hypodiploid with nonrandom losses of chromosomes #6, #7, #10, and #13. Structural rearrangements involved chromosomes #1 and #2, and there were three unidentified markers. The findings were compared with those described in other types of prostatic carcinoma.