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31.
We report the successful long-term engraftment of normal male donor bone marrow (BM) transfused into noncytoablated female mice, challenging the assumption that "niches" need to be created for marrow to engraft. We have used chromosomal banding and Southern blot analysis to identify transplanted male marrow cells, and shown the long-term stability of the chimeric marrows. Balb/C, BDF1, or CBA-J female hosts (no irradiation) received for 5 consecutive days 40 x 10(6) male cells (per day) of the same strain, and repopulation patterns were observed. Parallel studies were performed using tibia/femur equivalents of normal marrow or marrow from Balb/C mice pretreated 6 days previously with 150 mg/kg 5-fluorouracil (5-FU). Chromosome banding techniques showed that 5% to 46% of marrow cells were male 3 to 9 months posttransplant with normal donor marrow. Southern blot analysis, using the pY2 probe, showed continued engraftment at 21 to 25 months posttransplant, ranging from 15% to 42% male engrafted cells in marrow. Normal donor male marrow engrafted significantly better than 5-FU-pretreated male marrow as shown 1 to 12 months posttransplant in non-cytoablated female recipients. Percentages of male engrafted cells in BM ranged from 23% to 78% for recipients of normal donor marrow and from 0.1% to 39% for recipients of 5-FU marrow. Mean engraftment for 6 mice receiving normal marrow was 38%, whereas that for 6 mice receiving post-5-FU marrow was 8%, as assayed 1 to 3 months posttransplant. At 10 to 12 months, mean engraftment for the normal donor group was 46%, compared with 16% for the 5-FU group. The patterns of engraftment with normal and 5-FU marrow were similar for spleen and thymus. These results show that long-term chimerism can be established after transplantation of normal donor marrow to normal nonirradiated host mice and indicate that marrow spaces do not have to be created for successful engraftment. They suggest that transplanted marrow competes equally with host marrow for marrow space. Finally, these data show that post-5-FU Balb/C male marrow is markedly inferior in the repopulation of Balb/C female host marrow, spleen, and thymus, and suggest that this population of cells may not be the ideal population for gene transfer studies. 相似文献
32.
Duncan WC; Illingworth PJ; Young FM; Fraser HM 《Human reproduction (Oxford, England)》1998,13(9):2532-2540
The molecular mechanisms involved in luteolysis are still unclear in the
primate. This study aimed to investigate the effect of induced luteolysis
on the ovarian luteinizing hormone (LH) receptor and the steroidogenic
enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset
monkey. Luteolysis was induced in the mid-luteal phase either directly by
systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal
using systemic gonadotrophin releasing hormone antagonist (GnRHant)
treatment. The LH receptor was studied by isotopic mRNA in-situ
hybridization and in-situ ligand binding and 3beta-HSD expression was
studied using isotopic mRNA in-situ hybridization and immunohistochemistry.
Induced luteolysis was associated with a reduction in the expression of LH
receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a
reduction in the LH receptor (P < 0.05) and 3beta-HSD protein
concentrations within 24 h. There were no differences in the findings
whether luteolysis was induced with PGF2alpha or GnRHant. This study shows
that disparate mechanisms to induce luteolysis in the primate result in an
identical rapid loss of the LH receptor and 3beta-HSD. In conclusion,
induced luteolysis leads to rapid loss of the steroidogenic pathway in
luteal cells.
相似文献
33.
P. Denig F. M. Haaijer-Ruskamp H. Wesseling A. Versluis 《European journal of clinical pharmacology》1991,41(4):325-328
Summary To assess the influence that clinical trials may have on the introduction of new drugs into prescribing routines, the adoption of drugs has been studied in a university hospital in the Netherlands.A significant relation was found between the testing of semi-innovative drugs in clinical trials in the hospital and the introduction of these drugs into general use in the same hospital. No such relationship was found for innovative drugs. Employment in clinical trials only affected the frequency of adoption of semi-innovative drugs. It did not influence the quantity of their use once they had been adopted.The idea that the stimulating effect of clinical trials on the adoption of semi-innovative drugs is only due to acceleration of the adoption process was not confirmed.These findings support the idea that clinical trials can lower the barriers for adoption of semi-innovative drugs. 相似文献
34.
Possible mechanisms of valproate in migraine prophylaxis 总被引:7,自引:0,他引:7
FM Cutrer V Limmroth MA Moskowitz 《Cephalalgia : an international journal of headache》1997,17(2):93-100
Valproate has been shown to be an effective prophylactic treatment in migraine. Investigation of the mechanism of its antimigraine action is difficult due to the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valproate increases brain GABA levels and, in doing so, may suppress migraine-related events in the cortex, perivascular parasympathetics or trigeminal nucleus caudalis. There is experimental evidence that it suppresses neurogenic inflammation and directly attenuates nociceptive neurotransmission. In addition, valproate reportedly alters levels of excitatory and inhibitory neurotransmitters and exerts direct effects on neuronal membranes in vitro. Valproate's observed effect may ultimately result from a combination of actions at different loci. 相似文献
35.
Maat M Buysse CM Emonts M Spanjaard L Joosten KF de Groot R Hazelzet JA 《Critical care (London, England)》2007,11(5):R112
Background
To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands). 相似文献36.
Ruth H.E. De Smedt Tiny Jaarsma Flora M. Haaijer-Ruskamp Petra Denig 《Journal of cardiac failure》2010,16(2):135-141.e2
BackgroundGiven the importance of patient safety and well-being, we quantified the likelihood and type of medication changes observed after 5 possible adverse effects (AE) perceived by heart failure (HF) patients.Methods and ResultsWe conducted a retrospective cohort study using 18 months follow-up data from the Coordinating study evaluating Outcomes of Advising and Counseling in HF study on 754 patients previously hospitalized for HF (NYHA II-IV, mean age 70 years). Data used for this secondary analysis included problem checklists that patients had completed at 3 points in time, and medication data collected from chart review. Changes in potential causal cardiovascular medication and relevant alleviating medication were classified. Within group and relative risks (RR) for medication changes were calculated. Of the 754 patients, 50% reported dizziness, 44% dry cough, 19% nausea, 19% diarrhea, and 12% gout on the first checklist. Overall, the likelihood of a medication change was increased by 38% after a perceived AE. Dry cough had the highest increased likelihood of an associated cardiovascular medication change (RR 1.83, CI 1.35-2.49). Patients reporting gout had a four fold higher likelihood of alleviating medication started or intensified.ConclusionsA considerable number of HF patients perceived possible AE. However, the likelihood of medication being changed after a possible AE was rather low. There seems to be room for improving the management of AE. 相似文献
37.
38.
39.
Jasperien E. van Doormaal Patricia M.L.A. van den Bemt Rianne J. Zaal Bertil W. Lenderink Flora M. Haaijer-Ruskamp Peter G.M. Mol 《J Am Med Inform Assoc》2009,16(6):816-825
Objective
This study evaluated the effect of a Computerized Physician Order Entry system with basic Clinical Decision Support (CPOE/CDSS) on the incidence of medication errors (MEs) and preventable adverse drug events (pADEs).Design
Interrupted time-series design.Measurements
The primary outcome measurements comprised the percentage of medication orders with one or more MEs and the percentage of patients with one or more pADEs.Results
Pre-implementation, the mean percentage of medication orders containing at least one ME was 55%, whereas this became 17% post-implementation. The introduction of CPOE/CDSS has led to a significant immediate absolute reduction of 40.3% (95% CI: −45.13%; −35.48%) in medication orders with one or more errors.Pre-implementation, the mean percentage of admitted patients experiencing at least one pADE was 15.5%, as opposed to 7.3% post-implementation. However, this decrease could not be attributed to the introduction of CPOE/CDSS: taking into consideration the interrupted time-series design, the immediate change was not significant (−0.42%, 95% CI: −15.52%; 14.68%) because of the observed underlying negative trend during the pre-CPOE period of −4.04% [95% CI: −7.70%; −0.38%] per month.Conclusions
This study has shown that CPOE/CDSS reduces the incidence of medication errors. However, a direct effect on actual patient harm (pADEs) was not demonstrated. 相似文献40.
Magda Wullink Wemke Veldhuijzen Henny MJ van Schrojenstein Lantman - de Valk Job FM Metsemakers Geert-Jan Dinant 《BMC family practice》2009,10(1):1-10