Cancer chemotherapy administered via hemodialysis fistulas

End-stage renal failure (ESRF) patients can develop cancer before or after kidney disease occurs. Cancer chemotherapy often needs to be administered via the sort of central venous catheter that is normally avoided in ESRF care. Three cases are presented in which ESRF patients received chemotherapy for cancer via existing hemodialysis fistulas, and the consequences of central venous access in a fourth patient are discussed.     

Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. METHODS: DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. RESULTS: Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (chi 2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 ( P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA. CONCLUSIONS: These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. CLINICAL RELEVANCE: Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.     

Cell proliferation and neuronal differentiation in the dentate gyrus in juvenile and adult rats following traumatic brain injury

It is well known that the cognitive functions of juveniles recover to a greater extent than adult patients following traumatic brain injury (TBI). The exact mechanisms underlying this age-related disparity are unknown; however, we speculate that this improved recovery in juveniles following TBI may be associated with an endogenous neurogenic response in the hippocampus. We, therefore, examined the effects of TBI on cellular proliferation and differentiation in the dentate gyrus (DG) of the hippocampus in juvenile and adult rats following lateral fluid percussion injury (FPI). The temporal profile of the injury-induced proliferative response was determined using BrdU labeling at varying survival times. The differentiation of these newly generated cells was investigated using cell-type specific markers. We found that, following injury, there was a significant increase in cell proliferation in the DG in both injured juveniles and adults at 2 days post injury when compared to shams. When comparing the extent of cell proliferation between juveniles and adults following TBI, the absolute number of cells generated in the subgranular zone (SGZ) was far greater in the juveniles. Moreover, the percentage of newly generated cells in the SGZ that differentiated into neurons was nearly two times higher in the juveniles as compared to adults. Conversely, more glial differentiation was observed in the DG of adult rats. These findings provide compelling evidence that age-related differences in the neurogenic response to injury may underlie the differences observed in cognitive recovery in juvenile mammals as compared to adults following TBI.     

Angiotropism of human prostate cancer cells: implications for extravascular migratory metastasis

OBJECTIVES: To report several samples of invasive human prostate cancer showing angiotropism, and to use human prostate cancer cells stably expressing green fluorescence protein (GFP) in in vitro and in vivo models to assess the dissemination pathway of prostate cancer cells. MATERIALS AND METHODS: Malignant melanoma and prostate carcinoma cells can migrate along anatomical structures such as nerves; previous studies showed that melanoma cells can be perivascular, on the outside of the endothelium, i.e. they are angiotropic, which suggests the hypothesis that melanoma cells also may migrate along vascular channels, termed 'extravascular migratory metastasis' (EVMM). Thus we examined histologically 10 human prostatic carcinoma specimens for the presence of angiotropism. In vitro, the PC-3 prostate cancer cells were co-cultures with capillary-like structures. In vivo, PC-3 cells were implanted on the chick chorio-allantoic membrane (CAM). RESULTS: Histologically, in all 10 cases, angiotropism was detected at least focally within the tumour or at the advancing front of the tumour. In vitro, the PC-3 cells spread along the external surface of the vascular tubules; in vivo, PC-3 cells formed a cuff around some vessels a few millimetres beyond the tumour, showing angiotropism. Histopathology of the CAM confirmed the perivascular location of tumour cells and the absence of tumour cells within the vessel lumina. CONCLUSION: The presence of angiotropic tumour cells in human invasive prostate cancers, associated with the angiotropism of GFP prostate cancer cells cultivated in vitro and in vivo in angiogenic models, raises the possibility that some prostate tumour cells may migrate along the external surface of vessels as a mechanism of spread, i.e. EVMM.     

"Do good and talk about it". A CHRISTUS health study emphasizes the importance of telling our stories to the public

In a time of public scrutiny, it is paramount that Catholic health care organizations examine their commitments to their communities and effectively communicate community benefit activities to stakeholders-employees, physicians, patients, and the public. CHRISTUS Academy, a leadership development program at CHRISTUS Health, Irving, TX, conducted two studies regarding community benefit. The first researched community benefit practices at more than 20 highly respected, tax-exempt CHA- and VHA-member organizations, comparing them with the practices of about 40 publicly traded, for-profit organizations. The primary conclusion was that community benefit is not just about measuring the numbers-it is also about "telling the story." Unlike the for-profit organizations, tax-exempt health care organizations tend to struggle with adequately measuring and reporting their community contributions. In a second study, the academy surveyed CHRISTUS Health's employees and physicians regarding their knowledge of the system's commitment vis-à-vis identifying and meeting community needs. The vast majority said the system is important to the community and is actively involved in understanding and meeting the needs of the community. However, they also ranked the system lower in terms of working with other community organizations, being a leader in community health, and being known for sponsoring volunteer activities. These lower rankings indicate that the community benefit activities are not well publicized or known within the organization. Catholic health organizations must take an active approach in communicating their work to the public, the media, and each other. In doing so, they fulfill an integral part their mission.     

A study of work-related musculoskeletal case reports to The Health and Occupation Reporting network (THOR) from 2002 to 2003

BACKGROUND: Occupational musculoskeletal disorders are frequently seen by occupational physicians and rheumatologists, and there are well-established UK-based schemes set-up for reporting these conditions. An apparent fall in case reporting for work-related musculoskeletal disorders in Great Britain to The Health and Occupation Reporting network (THOR) was observed from 2002 to 2003. AIMS: To investigate changes in case reporting for musculoskeletal disorders sent by occupational physicians to Occupational Physicians Reporting Activity (OPRA) and by rheumatologists to Musculoskeletal Occupational Surveillance Scheme (MOSS) between 2002 and 2003. METHODS: Musculoskeletal cases returned by more than 800 physicians from Great Britain reporting to OPRA and MOSS in 2002-2003 were analysed. Changes in reporting are described at individual physician and group levels in: numbers of participants, levels of response, and numbers of case reports by disease category and major occupational and industrial groups. RESULTS: In 2002-2003, musculoskeletal disease was the most frequently reported major disease category in OPRA. Between 2002 and 2003, the proportion of musculoskeletal case reporting fell by 37% in OPRA, and 7% in MOSS. This fall was seen in many disease categories, across a wide range of occupations and industries. In OPRA, the greatest fall in reporting (74%) was for the category Raynaud's/Hand-Arm Vibration Syndrome/Vibration White Finger. CONCLUSIONS: The fall in occupational musculoskeletal case reporting between 2002 and 2003 cannot be explained by internal factors within the reporting system. This observation highlights the need for systematic investigation of trends in case reporting for work-related ill-health.     

Impact of Untreated Psychosis on Quality of Life in Patients with First-episode Schizophrenia

Despite increasing interest in the quality of life (QOL) of psychiatric patients in recent years, few studies have focused on the potential adverse effects of the illness on QOL during the period of untreated psychosis. Our study compares the QOL of patients with first-episode schizophrenia when they first presented to the psychiatric service with that of the normal population, and identifies possible relationships with various clinical parameters. One hundred and seventeen patients with schizophrenia (aged 14–28 years) who entered the Early Assessment Services for Young People with Psychosis (EASY) programme in Hong Kong from June 2001 to January 2004 were assessed with the MOS 36 item Short Form Health Survey (SF-36) and the World Health Organization Quality of Life Measure, abbreviated Hong Kong version (WHOQOL-BREF(HK)). We compared their SF-36 scores with controls from the normal population matched by age, sex, marital status and educational level. We assessed clinical parameters including positive, negative and depressive symptoms by the Positive and Negative Syndrome Scale (PANSS), the Scale for Assessment of Negative Symptoms (SANS), and the Montgomery and Asberg Depression Rating Scale (MADRS). When compared with matched controls from the normal population, significantly lower scores in all of the eight scales of the SF-36 were found in our patient group (p < 0.005). Various QOL domain scores had significant inverse correlations with the total MADRS score. However, there was no significant correlation with other clinical parameters. Young patients with first-episode schizophrenia have poorer QOL in the period of untreated psychosis than their counterparts in the community. Amongst various clinical parameters, the severity of depressive symptoms correlates most with QOL.