The pathogenesis of dialysis related amyloidosis remains unresolveddespite the identification of ß2-microglobulin (ß2M)as the major protein constituent, as well as other proteinsbeing present in the deposits. Among the latter we have assessedthe serum concentrations of 2-macroglobulin (2M) both in thebaseline stage and during the haemodialysis (HD) procedure.We have also assessed the influence of the membrane on 2M kinetics. Fifteen HD patients with histologically proven dialysis-relatedamyloidosis (DRA group) and 15 HD patients clinically and radiologicallyconsidered dialysis-related amyloidosis free (control group)were included in the baseline study. Blood was sampled the daybefore the second dialysis of the week and 2M, ß2Mand 1, antitrypsin were determined along with the routine biologicalanalysis of these patients. Serum 2M was greater in dialysis-relatedamyloidosis than in control patients (t = 2.35; P<0.026).Serum ß2M was similar in both groups. The serum 2Mand ß2M correlated in patients with dialysis-relatedamyloidosis (r = 0.64; P<0.01), while no correlation wasfound in controls (r = 0.17; NS). Stepwise analysis taking thepresence of dialysis-related amyloidosis as the dependent variableretained the serum 2M concentration as the first variable inthe model (F = 4.4; partial r = 0.38; P<0.046). The sameproteins were determined in another group of seven patients,before and hourly during HD as well as 2 and 8 h after the endof HD during nine consecutive dialyses (3 cycles of 3 HD eachusing AN69 and cuprophane membranes in a crossover design).Serum 2M significantly increased from hour 3 and continued toincrease 2 hours post-HD (+11% and +9% with AN69 and cuprophanerespectively; P<0.001). Total proteins peaked at hour 4 (+4% and +3% P<0.01) and decreased after HD. Serum ß2Msignificantly decreased with AN69 HD ( 29% P<0.001)and remained unchanged during cuprophane HD. In conclusion, significant increases in serum 2M are observedimmediately after and during the early post-dialysis periods,regardless of the membrane used. Further, serum 2M correlateswith ß2M only in patients with dialysis-related amyloidosis,and this variable was retained in the multivariate regressionanalysis to predict dialysis-related amyloidosis. Although thebaseline results require confirmation with larger studies, wepostulate that the present results are of relevance for dialysis-relatedamyloidosis pathogenesis since 2M, previously identified indialysis related amyloid deposits, is closely related to acute-phasereactant proteins, and interacts with the main infiltratingcells of the deposits (macrophages). 2M modifications couldrepresent a new manifestation of the inflammatory response tothe haemodialysis procedure. 相似文献
The search for alternatives to metered-dose inhalers has accelerated recently in a bid to find effective products that do not use chlorofluorocarbon (CFC) propellants. This paper reviews the factors to be considered in developing dry powder inhalers (DPIs), particularly the formulation, metering design and flow path in the device. The advantages and disadvantages of current DPIs are discussed and possible future approaches outlined. 相似文献
This is the first report of the association of spina bifida and eating disorders. Five patients were diagnosed rather late in the course of their illness. They all had been overweight premorbidly and had been urged to lose weight for years in order to improve their mobility. As they dieted, they experienced their weight loss as a source of power that could somehow compensate for their losses and neurologic limitations. They responded to a multidisciplinary intervention. Clinicians taking care of patients with spina bifida need to be cognizant that they may be at risk of developing an eating disorder. Such awareness should influence the quality of nutritional counseling (prevention aspect) and the clinical assessment of sudden weight loss (early intervention). 相似文献
A strong relationship exists between employee satisfaction and patients' perceptions of the quality of their care, measured in terms of their intent to return and to recommend the hospital to others. Employee dissatisfaction can negatively affect quality of care and have an adverse effect on patient loyalty and, thus hospital profitability. Therefore, health care marketers should regularly measure employee satisfaction as one way to monitor service quality. Health care marketers must work more closely with their human-resource departments to understand and influence employees' work environment and maintain a high level of job satisfaction. Marketers also should place an increased emphasis on both employee and patient perceptions of satisfaction when developing internal and external strategic marketing plans and formulating future research. 相似文献
Early concepts of fever as a major feature of illness range from those of Hippocrates to those present in the Bible and have influenced cultural attitudes during several major European pandemics of both black plague and tuberculosis, the "white plague" of the early 19th century. Evolving ideas of thermoregulation and fever in the 19th century followed the first extensive use of the clinical thermometer by Wunderlich. Experimental studies on the pathogenesis of fever during the last 30 years suggest that fever and certain aspects of both immunoregulation and inflammation are produced by a single hormone, the monokine interleukin-1, which has presumably been selected by evolution to protect the host against infection. 相似文献
Our experience of 54 patients with end-stage renal failure, who were treated with intermittent peritoneal dialysis and compared with patients maintained by haemodialysis over the years 1972 to 1978, has been reviewed. All patients received peritoneal dialysis for more than six weeks. The total experience was 32.8 patient dialysis-years, 48% as home dialysis. Peritoneal dialysis was used as an interim procedure in 19 patients who were waiting for haemodialysis. However, in 35 patients (particularly in the very young and elderly, and in situations of poor social support), recurrent peritoneal dialysis was chosen as the definitive dialysis therapy. Dialysis was assessed as "adequate" in all, but two, patients. The major complication of peritoneal dialysis was peritonitis, although its over-all incidence of 1.31 episodes per patient dialysis-year was low. An attack of peritonitis occurred every nine months of patient exposure, though the incidence of bacterial peritonitis averaged only once every 26 months. Fifty per cent of patients never had an episode of peritonitis. Intermittent peritoneal dialysis was associated with greater morbidity and mortality than haemodialysis, perhaps due, in part, to the older age of the peritoneal dialysis group. Intermittent peritoneal dialysis is a valuable adjunct to haemodialysis and transplantation in the treatment of end-stage renal failure. 相似文献
The HLA class I antigen-processing machinery (APM) plays a crucial role in the generation of peptides from endogenously synthesized proteins and in their presentation to cytotoxic T lymphocytes. The potential role of defects of APM components in immune escape mechanisms used by malignant cells has prompted us to analyze their expression in renal cell carcinoma (RCC) lesions with special emphasis on TAP because of its critical role in the loading of HLA class I antigens with peptides. Immunohistochemical staining of 51 formalin-fixed RCC lesions and autologous normal renal epithelium detected transporter associated with antigen processing (TAP)1 and tapasin deficiencies in 63 and 80% of the tumor lesions. Impaired low molecular weight protein (LMP)2 and LMP7 expression was found in 73 and 33% of the RCC lesions analyzed, respectively. In contrast to the high frequency of APM component down-regulation, HLA class I heavy chain and beta(2)-microglobulin defects were detected in only 12 and 10% of the lesions, respectively. Concomitant TAP1 and LMP2 deficiencies were found in approximately 57% of RCC lesions, whereas a coordinated down-regulation of all APM components occurred only in 5% of the tumor specimens analyzed. The presence of APM defects was independent of tumor stage and grade but varied significantly among the RCC subtypes. TAP abnormalities do not appear to be attributable to structural alterations because no mutations in TAP1 were detected in TAP1-deficient RCC lesions. These data suggest that TAP defects in RCC lesions are caused by regulatory abnormalities. Therefore, T-cell-based immunotherapy may benefit from the administration of cytokines that up-regulate TAP expression. 相似文献
Cell to cell communication via gap junctions is essential in the
maintenance of the homeostatic balance of multicellular organisms. Aberrant
intercellular gap junctional communication (GJIC) has been implicated in
tumor promotion, neuropathy and teratogenesis. Oxidative stress has also
been implicated in similar pathologies such as cancer. We report a
potential link between oxidative stress and GJIC. Hydrogen peroxide, a
known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells
with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible
as indicated by the complete recovery of GJIC with the removal of H2O2 via
a change of fresh media. Free radical scavengers, such as t-butyl alcohol,
propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2,
which indicated that the effects of H2O2 on GJIC was probably not a
consequence of aqueous free radical damage. The depletion of intracellular
GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of
glutathione- sufficient cells with H2O2 resulted in the
hyperphosphorylation of connexin43, which is the basic subunit of the
hexameric gap junction protein, as determined by Western blot analysis.
TPA, a well-known tumor promoter, also inhibits GJIC via
hyperphosphorylation of GJIC, which is a result of protein kinase-C
activation. However, H2O2 also induced hyperphosphorylation in
GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism
of GJIC inhibition must be different from the TPA-pathway and involves GSH.
相似文献
The Authors for the Live Organ Donor Consensus Group
JAMA. 2000;284:2919-2926.
Objective To recommend practice guidelines for transplantphysicians, primary care providers, health care planners, andall those who are concerned about the well-being of the liveorgan donor.
Participants An executive group representing the NationalKidney Foundation, and the American Societies of Transplantation,Transplant Surgeons, and Nephrology formed a steering committeeof 12 members to evaluate current practices of living donortransplantation of the kidney, pancreas, liver, intestine, andlung. The steering committee subsequently assembled more than100 representatives of the transplant community (physicians,nurses, ethicists, psychologists, lawyers, scientists, socialworkers, transplant recipients, and living donors) at a nationalconference held June 1-2, 2000, in Kansas City, Mo.
Consensus Process Attendees participated in 7 assignedwork groups. Three were organ specific (lung, liver, and kidney)and 4 were focused on social and ethical concerns (informedconsent, donor source, psychosocial issues, and live organ donorregistry). Work groups' deliberations were structured by a seriesof questions developed by the steering committee. Each workgroup presented its deliberations to an open plenary sessionof all attendees. This information was stored and shaped intoa statement circulated electronically to all attendees for theircomments, and finally approved by the steering committee forpublication. The term consensus is not meant to convey universalagreement of the participants. The statement identifies issuesof controversy; however, the wording of the entire statementis a consensus by approval of all attendees.
Conclusion The person who gives consent to be a live organdonor should be competent, willing to donate, free from coercion,medically and psychosocially suitable, fully informed of therisks and benefits as a donor, and fully informed of the risks,benefits, and alternative treatment available to the recipient.The benefits to both donor and recipient must outweigh the risksassociated with the donation and transplantation of the livingdonor organ.