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91.
Binnekade JM Vroom MB de Mol BA de Haan RJ 《Heart & lung : the journal of critical care》2003,32(3):190-196
OBJECTIVE: The forecasted shortage of nurses specialized in intensive care seriously threatens the service level in the intensive care units (ICUs). This problem might partly be solved by introducing nurses without ICU experience who can provide basic nursing care to relieve the workload of the ICU nurses. This prospective controlled study was set up to determine whether such an introduction causes a significant shift in the quality of care. DESIGN: A prospective observational study was conducted to measure possible changes in the quality of care by examining the number of predefined nursing errors per patient with an observational instrument, the Critical Nursing Situation Index (CNSI). The CNSI was randomly applied during a preassessment period, an intervention period, and a postassessment period. During the intervention period, 16 full time equivalent nurses were employed with the assignment to assist the ICU nurses with basic care activities for 6 months. SETTING: The study was conducted in a 30-bed ICU at the Academic Medical Center in Amsterdam. ANALYSIS: The effect of the employment of nurses was expressed as the difference in the incidence of CNSI scores between the preassessment period and the intervention period on the basis of the relative risk ratios. The results of the comparison between the preassessment and the postassessment period were used to express the consistency of the measure. RESULTS: The researchers completed 600 CNSI observations in 256 patients in 162 days. Overall incidence rates during the preassessment (13%; 1539/12 222) and postassessment (14%; 1554/11 327) period were comparable, whereas the intervention period showed a diminished overall incidence of 9% (1019/11 395). The overall relative risk (95% CL) was 0.70 (0.56/0.86), indicating a significant risk reduction during the intervention period. CONCLUSION: The employment of nurses without ICU training improved the quality of care. This positive effect was primarily explained by the increase in available nursing time. 相似文献
92.
The aim of this study was to expand the primitive and committed hematopoietic cell compartments in vivo in order to confer resistance of the blood cell forming system against the cytotoxic, cell cycle specific drug 5-fluorouracil (5-FU). Possible chemoprotective effects of such a pretreatment could result from increased numbers of hematopoietic cells, present before 5-FU administration. In addition, we hypothesized that an enhanced number of primitive and progenitor calls would result in a reduced cycling activity, ie, 5-FU sensitivity, of these same cells, due to normal physiological feedback loops. Administration of stem cell factor (SCF) plus interleukin-11 (IL-11) to mice was shown to result in expansion of the various immature cell compartments in marrow and, in particular, spleen. The total body content of the primitive cobblestone area forming cells (CAFC)-day 28 was increased to 140%, whereas the more committed cells (CAFC-day 7, erythroid and granuloid progenitors) were increased to 500%. This in vivo expansion resulted in a decreased 5-FU sensitivity of the hematopoietic system. In particular, mice that had received 5-FU 24 hours after discontinuation of growth factor pretreatment showed significantly less toxicity of committed cell stages. Compared with mice not pretreated, it appeared that in pretreated mice, 24 hours after 5-FU administration, the absolute number, but also the fraction of surviving CAFC, was much higher in both marrow and spleen. This was caused by a decrease in the cycling activity of all primitive cell subsets. To explore the possible use of this finding in a chemotherapeutic setting, we determined the interval between two subsequent doses of 5-FU (160 mg/kg) that was required to prevent drug- induced mortality. When control mice received a second dose of 5-FU 7, 10, or 14 days after the first, respectively 0%, 20%, and 80% survived. In contrast, 40% and 100% of mice that received SCF + IL-11 before the first dose of 5-FU, survived a second dose of 5-FU given respectively after 7 or 10 days. To assess whether chemoprotection in this setting could be ascribed to protection of the hematopoietic system, we transplanted a high number of normal bone marrow cells (sufficient to compensate for any hematopoietic deficiency) to normal and pretreated mice after they had been administered 2 doses of 5-FU, given 7 days apart. Bone marrow transplantation (BMT) could only rescue 50% of mice not pretreated, showing that a significant part of the mortality was because of nonhematologic toxicity. However, a BMT given to growth factor pretreated mice saved all mice, indicating that in this setting SCF + IL-11 had additional protective effects on cell systems other than hematopoiesis. In conclusion, our study showed fundamental knowledge about the behavior of primitive cells in vivo and has shown that manipulation of these and other cell compartments with appropriate growth factors may confer resistance against cytotoxic drugs. 相似文献
93.
94.
Crystal structures of TAFI elucidate the inactivation mechanism of activated TAFI: a novel mechanism for enzyme autoregulation
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Thrombin-activatable fibrinolysis inhibitor (TAFI) is a pro-metallocarboxypeptidase that can be proteolytically activated (TAFIa). TAFIa is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. We studied the intrinsic instability of TAFIa by solving crystal structures of TAFI, a TAFI inhibitor (GEMSA) complex and a quadruple TAFI mutant (70-fold more stable active enzyme). The crystal structures show that TAFIa stability is directly related to the dynamics of a 55-residue segment (residues 296-350) that includes residues of the active site wall. Dynamics of this flap are markedly reduced by the inhibitor GEMSA, a known stabilizer of TAFIa, and stabilizing mutations. Our data provide the structural basis for a model of TAFI auto-regulation: in zymogen TAFI the dynamic flap is stabilized by interactions with the activation peptide. Release of the activation peptide increases dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg302. This represents a novel mechanism of enzyme control that enables TAFI to regulate its activity in plasma in the absence of specific inhibitors. 相似文献
95.
96.
Wijnhoven HA Kriegsman DM Hesselink AE de Haan M Schellevis FG 《Respiratory medicine》2003,97(5):468-475
This study examines the association between somatic co-morbidity and both general and disease-specific health-related quality of life (HRQoL) in patients with asthma and chronic obstructive pulmonary disease (COPD). A cross-sectional analysis was done among 161 COPD patients and 395 asthma patients, aged 40-75 years, recruited from general practice. In the total study population, 47% had no, 32% had one, and 21% had two or more somatic co-morbid conditions, with no significant differences between asthma and COPD patients. Co-morbidity appeared to be associated with poor disease-specific HRQoL in asthma [odds ratio (OR) = 2.08 (1.37-3.18)] and with poor general HRQoL in asthma [OR = 2.96 (1.93-4.53)] and COPD [1.81 (0.91-3.60)] patients. Poorest HRQoL was found in patients with more than one co-morbid condition. Cardiac disease and hypertension were associated with poor disease-specific HRQoL in asthma. Of all co-morbid conditions, musculoskeletal disorders were most strongly associated with poor general HRQoL. Cardiac disease was found to be associated with general and disease-specific HRQoL in asthma but not in COPD. In studies on patients with asthma or COPD aged 40-75 years, co-morbidity should be treated as a determinant of HRQoL. 相似文献
97.
Lennart B. van Rijssen Maurice J. Zwart Susan van Dieren Thijs de Rooij Bert A. Bonsing Koop Bosscha Ronald M. van Dam Casper H. van Eijck Michael F. Gerhards Josephus J. Gerritsen Erwin van der Harst Ignace H. de Hingh Koert P. de Jong Geert Kazemier Joost Klaase Berendina M. van der Kolk Cornelis J. van Laarhoven Misha D. Luyer Peter P. Coene 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2018,20(8):759-767
Background
In the mandatory nationwide Dutch Pancreatic Cancer Audit, rates of major complications and Failure to Rescue (FTR) after pancreatoduodenectomy between low- and high-mortality hospitals are compared, and independent predictors for FTR investigated.Methods
Patients undergoing pancreatoduodenectomy in 2014 and 2015 in The Netherlands were included. Hospitals were divided into quartiles based on mortality rates. The rate of major complications (Clavien-Dindo ≥3) and death after a major complication (FTR) were compared between these quartiles. Independent predictors for FTR were identified by multivariable logistic regression analysis.Results
Out of 1.342 patients, 391 (29%) developed a major complication and in-hospital mortality was 4.2%. FTR occurred in 56 (14.3%) patients. Mortality was 0.9% in the first hospital quartile (4 hospitals, 327 patients) and 8.1% in the fourth quartile (5 hospitals, 310 patients). The rate of major complications increased by 40% (25.7% vs 35.2%) between the first and fourth hospital quartile, whereas the FTR rate increased by 560% (3.6% vs 22.9%). Independent predictors of FTR were male sex (OR = 2.1, 95%CI 1.2–3.9), age >75 years (OR = 4.3, 1.8–10.2), BMI ≥30 (OR = 2.9, 1.3–6.6), histopathological diagnosis of periampullary cancer (OR = 2.0, 1.1–3.7), and hospital volume <30 (OR = 3.9, 1.6–9.6).Conclusions
Variations in mortality between hospitals after pancreatoduodenectomy were explained mainly by differences in FTR, rather than the incidence of major complications. 相似文献98.
Simon J Furney Samra Turajlic Gordon Stamp Mahrokh Nohadani Anna Carlisle J Meirion Thomas Andrew Hayes Dirk Strauss Martin Gore Joost van den Oord James Larkin Richard Marais 《The Journal of pathology》2013,230(3):261-269
Mucosal melanoma displays distinct clinical and epidemiological features compared to cutaneous melanoma. Here we used whole genome and whole exome sequencing to characterize the somatic alterations and mutation spectra in the genomes of ten mucosal melanomas. We observed somatic mutation rates that are considerably lower than occur in sun‐exposed cutaneous melanoma, but comparable to the rates seen in cancers not associated with exposure to known mutagens. In particular, the mutation signatures are not indicative of ultraviolet light‐ or tobacco smoke‐induced DNA damage. Genes previously reported as mutated in other cancers were also mutated in mucosal melanoma. Notably, there were substantially more copy number and structural variations in mucosal melanoma than have been reported in cutaneous melanoma. Thus, mucosal and cutaneous melanomas are distinct diseases with discrete genetic features. Our data suggest that different mechanisms underlie the genesis of these diseases and that structural variations play a more important role in mucosal than in cutaneous melanomagenesis. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
99.
Carolien M. S. Schophuizen Martijn J. Wilmer Jitske Jansen Lena Gustavsson Constanze Hilgendorf Joost G. J. Hoenderop Lambert P. van den Heuvel Rosalinde Masereeuw 《Pflügers Archiv : European journal of physiology》2013,465(12):1701-1714
Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP+). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP+ uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP+ uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC50?=?44?±?2 μM). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 μM ASP+, which demonstrated competitive or mixed type of interaction (K i?=?93 ± 16 μM). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP+ uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia. 相似文献
100.