461 research outputs found
Information from physicians and retention of information by patients – Obstacles to the awareness of patients of progressing disease when life is near the end
Get PDF<p>Abstract</p> <p>Background</p> <p>Discrepancies between the information that patients have received and the patients' awareness of their condition have frequently been observed in literature and given a number of different explanations. The chief contribution of this study is that by following patients over time it is possible not only to notice any changes in the patients' knowledge or awareness of their disease, but also to investigate the interview material for possible reasons for those changes. Since the study is based on two different groups of patients it will also be possible to notice if the category of disease matters for patients' awareness of their condition.</p> <p>Methods</p> <p>Twelve patients with malign haematological diseases or lung cancer were followed with interviews from diagnosis to cure or death, or at most for two years. The method is qualitative. Semi-structured interviews were conducted, transcribed into written text, and then used for a qualitative content analysis.</p> <p>Results</p> <p>During the process of analysis four different expressions (subcategories) emerged about the awareness of patients concerning their health status: informed and aware, not informed and not aware, aware though not informed, or not aware though informed. Then the search started for obstacles to the awareness of patients regarding their progressing disease and approaching death. Four kinds of obstacles were found: due to the physician, the patient, the physician and the patient in collusion, or neither to the physician nor the patient but the insidious way in which lung cancer (mostly) and haematological malignancies (occasionally) progress.</p> <p>Conclusion</p> <p>To optimize the care of patients who wish to be informed and aware during their disease, it is important that the health care staff recognizes potential obstacles to the awareness of patients in order to minimize such obstacles. The physicians could improve their communication with patients with life-threatening diseases, and avoid having a narrow focus on the treatment calendar. The patients could be encouraged to have a more proactive attitude in their communication with their physician.</p
Uptake in cancer screening programmes:a priority in cancer control
Get PDFAchieving adequate levels of uptake in cancer screening requires a variety of approaches that need to be shaped by the characteristics of both the screening programme and the target population. Strategies to improve uptake typically produce only incremental increases. Accordingly, approaches that combine behavioural, organisational and other strategies are most likely to succeed. In conjunction with a focus on uptake, providers of screening services need to promote informed decision making among invitees. Addressing inequalities in uptake must remain a priority for screening programmes. Evidence informing strategies targeting low-uptake groups is scarce, and more research is needed in this area. Cancer screening has the potential to make a major contribution to early diagnosis initiatives in the United Kingdom, and will best be achieved through uptake strategies that emphasise wide coverage, informed choice and equitable distribution of cancer screening services
Biochemical effect evaluation of perfluorooctane sulfonic acid-contaminated wood mice (Apodemus sylvaticus).
Get PDFWood mice (Apodemus sylvaticus) were captured at Blokkersdijk, a nature reserve in the immediate vicinity of a fluorochemical plant in Antwerp, Belgium, and at Galgenweel, 3 kilometers farther away. The liver perfluorooctane sulfonic acid (PFOS) concentrations in the Blokkersdijk mice were extremely high (0.47-178.55 micro g/g wet weight). Perfluorononanoic, perfluorodecanoic, perfluoroundecanoic, and perfluorododecanoic acids were found sporadically in the liver tissue of the Blokkersdijk mice. The liver PFOS concentrations at Galgenweel were significantly lower than those at Blokkersdijk (0.14-1.11 micro g/g wet weight). Further results suggest sex independence of the liver PFOS levels, increased levels of PFOS bioaccumulation in older mice, and maternal PFOS transfer to the young. Several liver end points were significantly elevated in the Blokkersdijk mice: liver weight, relative liver weight, peroxisomal beta-oxidation activity, microsomal lipid peroxidation level, and mitochondrial fraction protein content. For the mitochondrial fraction catalase activity, no significant difference between locations was found. The liver weight, relative liver weight, and liver microsomal lipid peroxidation level increased significantly with the liver PFOS concentration. No indications for PFOS-mediated effects on the serum triglyceride, cholesterol, or potassium levels were obtained. The liver PFOS concentration was negatively related to the serum alanine aminotransferase activity
SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer
Get PDFPancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer
Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice
Get PDFIntroduction: Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics.Methods: We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of latency-associated peptide and transforming growth factor beta 1 (TGFβ1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography.Results: The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGFβ1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice.Conclusions: These data establish a link between hormonal response, proliferation, modulation of MMP activity and maintenance of basement membrane integrity that depend on a balance in the expression levels of PR-A and PR-B isoforms. Notably, concomitant increased proliferation, due to inhibition of TGFβ1 activation, and loss of basement membrane integrity, via increased MMP-2 activity, appear to be prerequisites for the PR-A hyperplastic phenotype.Fil: Simian, Marina. Lawrence Berkeley National Laboratory; Estados Unidos. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Bissell, Mina J.. Lawrence Berkeley National Laboratory; Estados UnidosFil: Barcellos Hoff, Mary H.. Lawrence Berkeley National Laboratory; Estados Unidos. NYU Langone Medical Center; Estados UnidosFil: Shyamala, Gopalan. Lawrence Berkeley National Laboratory; Estados Unido
Blood volume measurement with indocyanine green pulse spectrophotometry: dose and site of dye administration
Get PDF(1) To determine the optimal administration site and dose of indocyanine green (ICG) for blood volume measurement using pulse spectrophotometry, (2) to assess the variation in repeated blood volume measurements for patients after subarachnoid hemorrhage and (3) to evaluate the safety and efficacy of this technique in patients who were treated for an intracranial aneurysm. Four repeated measurements of blood volume (BV) were performed in random order of bolus dose (10 mg or 25 mg ICG) and venous administration site (peripheral or central) in eight patients admitted for treatment of an intracranial aneurysm. Another five patients with subarachnoid hemorrhage underwent three repeated BV measurements with 25 mg ICG at the same administration site to assess the coefficient of variation. The mean +/- SD in BV was 4.38 +/- 0.88 l (n = 25) and 4.69 +/- 1.11 l (n = 26) for 10 mg and 25 mg ICG, respectively. The mean +/- SD in BV was 4.59 +/- 1.15 l (n = 26) and 4.48 +/- 0.86 l (n = 25) for central and peripheral administration, respectively. No significant difference was found. The coefficient of variance of BV measurement with 25 mg of ICG was 7.5% (95% CI: 3-12%). There is no significant difference between intravenous administration of either 10 or 25 mg ICG, and this can be injected through either a peripheral or central venous catheter. The 7.5% coefficient of variation in BV measurements determines the detectable differences using ICG pulse spectrophotometr
The Influence of Mirror-Visual Feedback on Training-Induced Motor Performance Gains in the Untrained Hand
Get PDFThe well-documented observation of bilateral performance gains following unilateral motor training, a phenomenon known as cross-limb transfer, has important implications for rehabilitation. It has recently been shown that provision of a mirror image of the active hand during unilateral motor training has the capacity to enhance the efficacy of this phenomenon when compared to training without augmented visual feedback (i.e., watching the passive hand), possibly via action observation effects [1]. The current experiment was designed to confirm whether mirror-visual feedback (MVF) during motor training can indeed elicit greater performance gains in the untrained hand compared to more standard visual feedback (i.e., watching the active hand). Furthermore, discussing the mechanisms underlying any such MVF-induced behavioural effects, we suggest that action observation and the cross-activation hypothesis may both play important roles in eliciting cross-limb transfer. Eighty participants practiced a fast-as-possible two-ball rotation task with their dominant hand. During training, three different groups were provided with concurrent visual feedback of the active hand, inactive hand or a mirror image of the active hand with a fourth control group receiving no training. Pre- and post-training performance was measured in both hands. MVF did not increase the extent of training-induced performance changes in the untrained hand following unilateral training above and beyond those observed for other types of feedback. The data are consistent with the notion that cross-limb transfer, when combined with MVF, is mediated by cross-activation with action observation playing a less unique role than previously suggested. Further research is needed to replicate the current and previous studies to determine the clinical relevance and potential benefits of MVF for cases that, due to the severity of impairment, rely on unilateral training programmes of the unaffected limb to drive changes in the contralateral affected limb
Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer
Get PDFPurpose: Zoledronic acid (ZA) or denosumab treatment reduces skeletal-related events; however, the safety of prolonged therapy has not been adequately studied. Here, we describe safety results of extended denosumab therapy in patients with bone metastases from the open-label extension phase of two phase 3 trials. Methods: Patients with metastatic breast or prostate cancer received subcutaneous denosumab 120 mg Q4W or intravenous ZA 4 mg Q4W in a double-blinded fashion. Denosumab demonstrated superior efficacy in the blinded treatment phase; thus, patients were offered open-label denosumab for up to an additional 2 years. Results: Cumulative median (Q1, Q3) denosumab exposure was 19.1 (9.2, 32.2) months in the breast cancer trial (n = 1019) and 12.0 (5.6, 21.3) months in the prostate cancer trial (n = 942); 295 patients received denosumab for >3 years. No new safety signals were identified during the open-label phase, or among patients who switched from ZA to denosumab. During the blinded treatment phase, exposure-adjusted subject incidences of osteonecrosis of the jaw (ONJ) were 49 (1.9 %) and 31 (1.2 %) in the denosumab and ZA groups, respectively. In total, 32 (6.9 %) and 25 (5.5 %) new cases of ONJ (not adjusted for exposure) were reported for patients continuing and switching to denosumab, respectively. The incidences of hypocalcemia were 4.3 and 3.1 %, in patients continuing and switching to denosumab, respectively. Conclusion: These results describe the safety profile of denosumab after long-term exposure, or after switching to denosumab from ZA. No new safety signals were identified. Hypocalcemia rates were similar in the blinded treatment and open-label phases. ONJ rates increased with increasing exposure to antiresorptives, consistent with previous reports
RON5 is critical for organization and function of the Toxoplasma moving junction complex
Get PDFApicomplexans facilitate host cell invasion through formation of a tight-junction interface between parasite and host plasma membranes called the moving junction (MJ). A complex of the rhoptry neck proteins RONs 2/4/5/8 localize to the MJ during invasion where they are believed to provide a stable anchoring point for host penetration. During the initiation of invasion, the preformed MJ RON complex is injected into the host cell where RON2 spans the host plasma membrane while RONs 4/5/8 localize to its cytosolic face. While much attention has been directed toward an AMA1-RON2 interaction supposed to occur outside the cell, little is known about the functions of the MJ RONs positioned inside the host cell. Here we provide a detailed analysis of RON5 to resolve outstanding questions about MJ complex organization, assembly and function during invasion. Using a conditional knockdown approach, we show loss of RON5 results in complete degradation of RON2 and mistargeting of RON4 within the parasite secretory pathway, demonstrating that RON5 plays a key role in organization of the MJ RON complex. While RON8 is unaffected by knockdown of RON5, these parasites are unable to invade new host cells, providing the first genetic demonstration that RON5 plays a critical role in host cell penetration. Although invasion is not required for injection of rhoptry effectors into the host cytosol, parasites lacking RON5 also fail to form evacuoles suggesting an intact MJ complex is a prerequisite for secretion of rhoptry bulb contents. Additionally, while the MJ has been suggested to function in egress, disruption of the MJ complex by RON5 depletion does not impact this process. Finally, functional complementation of our conditional RON5 mutant reveals that while proteolytic separation of RON5 N- and C-terminal fragments is dispensable, a portion of the C-terminal domain is critical for RON2 stability and function in invasion
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