Cellular stress-response modulators in the acute rat model of peritoneal dialysis

Cytotoxicity of peritoneal dialysis fluids (PDF) not only results in cellular injury, but also induces heat-shock proteins (HSP), the main effectors of the cellular stress response. This study investigated effects of modulation of mesothelial HSP expression on peritoneal membrane integrity during acute PDF exposure. In the acute in vivo rat model of peritoneal dialysis (PD), either the HSP coinducer indomethacin or the HSP suppressor quercetin was added to standard PDF (CAPD 3, Fresenius, Germany). HSP-72 expression, number of detached mesothelial cells, and peritoneal protein loss were evaluated at the end of a 4-h dwell time. Compared with pure PDF exposure, addition of indomethacin resulted in increased expression of mesothelial HSP-72, reduced mesothelial cell exfoliation, and reduced peritoneal protein loss. Addition of quercetin resulted in decreased expression of HSP-72, increased mesothelial cell exfoliation, and higher peritoneal protein loss. Differences were statistically significant between indomethacin-treated and quercetin-treated rats. Mesothelial HSP expression was related to markers of peritoneal membrane integrity upon in vivo PDF exposure, consistent with HSP-mediated cytoprotection. These data clearly demonstrate the potential for clinically feasible pharmacologic interventions with the cellular stress response as a novel therapeutic approach to improve PD outcome.     

Quality of out-of-hospital palliative emergency care depends on the expertise of the emergency medical team—a prospective multi-centre analysis

Background  

The number of palliative care patients who live at home and have non-curable life-threatening diseases is increasing. This is largely a result of modern palliative care techniques (e.g. specialised out-of-hospital palliative medical care services), changes in healthcare policy and the availability of home care services. Accordingly, pre-hospital emergency physicians today are more likely to be involved in out-of-hospital emergency treatment of palliative care patients with advanced disease.     

Expression of the apoptosis inhibitor livin in renal cell carcinomas: correlations with pathology and outcome.

Livin has recently been identified as a member of the inhibitor of apoptosis family expressed in several types of cancer but not in most benign tissues. Expression levels of livin were associated with prognosis in various malignancies, but livin expression and its prognostic relevance have not been evaluated in renal cell carcinomas (RCC). In a cohort of 152 RCC patients, we analyzed the relative expression of livin and its splicing variants by real-time RT-PCR and Western blot in tumor and adjacent normal renal tissue specimens. Livin expression was detected in 59 (38.8%) of 152 RCC specimens but in none of the normal samples. Both splicing variants were present in the livin-positive RCC specimens. Livin expression levels did not correlate with pathological or clinical parameters and were not predictive of patient outcome. Our findings suggest that livin expression in RCC is not of prognostic relevance. Further studies to clarify the role of livin expression in RCC and its potential value as a target for immune-mediated tumor destruction are warranted.     

Combined 1p/19q loss in oligodendroglial tumors: predictive or prognostic biomarker?

PURPOSE: The combined loss of genetic material on chromosomes 1p and 19q is strongly associated with favorable outcome in patients with WHO grade 3 anaplastic oligodendroglial tumors. The prognostic value of 1p/19q loss in WHO grade 2 oligodendroglial tumors is less well defined. Importantly, the possible effect of combined 1p/19q loss has not been studied in patients who were not treated with radiotherapy or chemotherapy. EXPERIMENTAL DESIGN: Seventy-six patients with oligodendroglioma (n = 33), oligoastrocytoma (n = 30), anaplastic oligodendroglioma (n = 6), or anaplastic oligoastrocytoma (n = 7) were identified who had not received radiotherapy or chemotherapy after their first operation until the end of follow-up or until the first progression and had tissue for 1p/19q status available. 1p/19q status was assessed by multiplex ligation-dependent probe amplification. RESULTS: After a median follow-up of 3.8 years, progressive disease was documented in 34 patients. The estimated median progression-free survival was 4.6 years. Fifty-eight of the 76 patients had a combined loss of 1p and 19q. The absence or presence of combined 1p/19q loss was not prognostic for progression-free survival using multivariate adjustment for histology, extent of resection, and gender. CONCLUSIONS: Combined 1p/19q loss is not a sensitive prognostic biomarker in patients with oligodendroglial tumors who do not receive radiotherapy or chemotherapy. The gene products lost as a consequence of this codeletion may include mediators of resistance to genotoxic therapies. Alternatively, 1p/19q loss might be an early oncogenic lesion promoting the formation of glial neoplasms, which retain high sensitivity to genotoxic stress.     

Paroxetine with pindolol augmentation: a double-blind, randomized, placebo-controlled study in depressed in-patients.

Pindolol, a 5-HT1A autoreceptor antagonist, given in combination with selective serotonin reuptake inhibitors (SSRIs), may enhance and/or accelerate the therapeutic efficacy of SSRIs. Fifty patients, meeting ICD-10 criteria for major depressive disorder or bipolar depression, were enrolled in our randomized, placebo-controlled, double-blind trial. One group received paroxetine plus pindolol (2.5 mg t.i.d.), and the other group received paroxetine plus placebo. The proportion of patients with sustained response (>or=50% reduction of baseline HAM-D 17 score maintained until the endpoint; p=0.252) and the proportion of patients with remission (HAM-D 17 相似文献   

Self‐application of single‐use eyedrop containers in an elderly population: comparisons with standard eyedrop bottle and with younger patients

Purpose: To test whether patients aged ≥80 years can safely and successfully apply eyedrops from a single‐use eyedrop container without support, and to compare the results with those of younger patients using single‐use containers and older patients using standard eyedrop bottles. Methods: Patients aged ≥80 years who had no physical or mental conditions hindering self‐application of eyedrops and actually did so because of glaucoma or dry eyes were included consecutively in the study group (n = 44) in order to perform self‐application of eyedrops from single‐use eyedrop containers. Patients were observed meticulously by two investigators, who documented practical problems during the procedure in a checklist. In control group A (n = 22), glaucoma or sicca patients aged between 50 and 65 years applied drops from single‐use eyedrop containers; in control group B (n = 28), glaucoma or sicca patients aged ≥80 years used a traditional eyedrop bottle. Results: Successful application of the drops into the conjunctival sac was achieved by 57% in the study group (95% and 89% in control groups A and B, respectively). Scratching of the eyedrop container along the conjunctiva or cornea was observed in 68% of the study group (41% and 61% in control groups A and B, respectively). Frequency of problems during opening and self‐application of single‐use eyedrop containers in the study group showed an inverse correlation to visual acuity in the better eye and previous experience with this kind of eyedrop container. Conclusion: Older patients have massive problems in self‐administering eyedrops from single‐use containers. Factors influencing the success of self‐application may include the patient’s previous experience with this kind of eyedrop container and the patient’s visual acuity.