Beyond bisphosphonates: photodynamic therapy structurally augments metastatically involved vertebrae and destroys tumor tissue

Breast cancer patients commonly develop metastases in the spine, which compromises its mechanical stability and can lead to skeletal related events. The current clinical standard of treatment includes the administration of systemic bisphosphonates (BP) to reduce metastatically induced bone destruction. However, response to BPs can vary both within and between patients, which motivates the need for additional treatment options for spinal metastasis. Photodynamic therapy (PDT) has been shown to be effective at treating metastatic lesions secondary to breast cancer in an athymic rat model, and is proposed as a treatment for spinal metastasis. The objective of this study was to determine the effect of PDT, alone or in combination with previously administered systemic BPs, on the structural and mechanical integrity of both healthy and metastatically involved vertebrae. Human breast carcinoma cells (MT-1) were inoculated into athymic rats (day 0). At 14 days, a single PDT treatment was administered, with and without previous BP treatment at day 7. In addition to causing tumor necrosis in metastatically involved vertebrae, PDT significantly reduced bone loss, resulting in strengthening of the vertebrae compared to untreated controls. Combined treatment with BP + PDT further enhanced bone architecture and strength in both metastatically involved and healthy bone. Overall, the ability of PDT to both ablate malignant tissue and improve the structural integrity of vertebral bone motivates its consideration as a local minimally invasive treatment for spinal metastasis secondary to breast cancer.     

Comparing Two Approaches to Acquiring HIV-Risk Data from Puerto Rican Women with Severe Mental Illness

Renewed interest has been expressed by researchers in mixed-method assessment that employs both quantitative and qualitative techniques in an expansive style that utilizes a variety of tactics to address research questions. Participants consisted of Puerto Rican women with severe mental illness living in Cuyahoga County, Ohio. The women were shadowed over a 2-year period to observe and verify behaviors that were self-reported using standardized instruments in semi-structured interviews. Concurrent criterion-related validity was employed to determine the extent of the correlation between responses obtained from the two approaches. Forty-four percent of the women were diagnosed with major depression and the mean overall GAF score was 58.5 ± 14.5. A comparison of the data collected using the different methodologies revealed that inconsistent and contradictory responses are not uncommon. The mixed-method design provided a more complete way of obtaining HIV-risk behavior data. Researchers and clinicians could benefit from mixed methods research that can provide greater opportunities to obtain data of a sensitive nature.     

Localization and loss-of-function implicates ciliary proteins in early, cytoplasmic roles in left-right asymmetry.

Left-right asymmetry is a crucial feature of the vertebrate body plan. While much molecular detail of this patterning pathway has been uncovered, the embryonic mechanisms of the initiation of asymmetry, and their evolutionary conservation among species, are still not understood. A popular recent model based on data from mouse embryos suggests extracellular movement of determinants by ciliary motion at the gastrulating node as the initial step. An alternative model, driven by findings in the frog and chick embryo, focuses instead on cytoplasmic roles of motor proteins. To begin to test the latter hypothesis, we analyzed the very early embryonic localization of ciliary targets implicated in mouse LR asymmetry. Immunohistochemistry was performed on frog and chick embryos using antibodies that have (KIF3B, Polaris, Polycystin-2, acetylated alpha-tubulin) or have not (LRD, INV, detyrosinated alpha-tubulin) been shown to detect in frog embryos only the target that they detect in mammalian tissue. Immunohistochemistry revealed localization signals for all targets in the cytoplasm of cleavage-stage Xenopus embryos, and in the base of the primitive streak in chick embryos at streak initiation. Importantly, several left-right asymmetries were detected in both species, and the localization signals were dependent on microtubule and actin cytoskeletal organization. Moreover, loss-of-function experiments implicated very early intracellular microtubule-dependent motor protein function as an obligate aspect of oriented LR asymmetry in Xenopus embryos. These data are consistent with cytoplasmic roles for motor proteins in patterning the left-right axis that do not involve ciliary motion.     

Peritoneal dialysis in infants and children

Pediatric renal failure patients can be restored to health with peritoneal dialysis more easily, more comfortably, and more safely than with hemodialysis. During the past 3.5 years, we have treated 22 children with either acute (less than 30 days) or chronic (greater than 30 days) peritoneal dialysis (PD) at Henrietta Egleston Hospital for Children. They ranged in age from 2 weeks to 15 1/6 years, mean 5.2 years. The indications for acute dialysis were renal failure following cardiac surgery (4); hemolytic-uremic syndrome (4); and renal failure associated with bromide intoxication (1), congenital urethral stricture (1), or bronchopulmonary dysplasia (1). Chronic dialysis was utilized for end-stage renal disease caused by glomerulonephritis (5), chronic infection (2), hemolytic-uremic syndrome (1), cystinosis (1), congenital renal artery stenosis (1), and unknown etiology (1). Thirty-four adult or pediatric Tenckhoff catheters were utilized to deliver PD for from 6 to 551 days (18 months). Pediatric Tenckhoff catheters must be pre-measured in order to have the Dacron cuffs glued to the appropriate position on the catheter (7-12 cm from the end) to fit the child. There were seven catheter-related infections in four patients; three required catheter revision and four were treated medically. There were eight catheter-related mechanical problems, all of which required re-operation. All of those on chronic PD and seven of those on acute PD survived for an overall survival of 82 per cent. All surviving patients have been restored to health either by recovery of renal function (6 patients), renal transplantation (8 patients), or maintenance of chronic ambulatory peritoneal dialysis (4 patients).