Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice [see comments]

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.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

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.      

Impact of clinical trials on the adoption of new drugs within a university hospital

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.     

Possible mechanisms of valproate in migraine prophylaxis

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.     

Improved survival of children with sepsis and purpura: effects of age,gender, and era

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).     

The Impact of Perceived Adverse Effects on Medication Changes in Heart Failure Patients

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.     

The Influence that Electronic Prescribing Has on Medication Errors and Preventable Adverse Drug Events: an Interrupted Time-series Study

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.     

Doctor-patient communication with people with intellectual disability - a qualitative study

Background

Patients' priorities and views on quality care are well-documented in Western countries but there is a dearth of research in this area in the East. The aim of the present study was to explore Chinese patients' views on quality of primary care consultations in Hong Kong and to compare these with the items in the CARE measure (a process measure of consultation quality widely used in the UK) in order to assess the potential utility of the CARE measure in a Chinese population.

Methods

Individual semi-structured interviews were conducted on 21 adult patients from 3 different primary care clinics (a public primary healthcare clinic, a University health centre, and a private family physician's clinic). Topics discussed included expectations, experiences, and views about quality of medical consultations. Interviews were typed verbatim, and a thematic approach was taken to identify key issues. These identified issues were then compared with the ten CARE measure items, using a CARE framework: Connecting (Care Measure items 1–3), Assessing (item 4), Responding (items 5,6), and Empowering (items 7–10).

Results

Patients judged doctors in terms of both the process of the consultation and the perceived outcomes. Themes identified that related to the interpersonal process of the consultation fitted well under the CARE framework; Connecting and communicating (18/21 patients), Assessing holistically (10/21 patients), Responding (18/21 patients) and Empowering (19/21 patients). Patients from the public clinic, who were generally of lower socio-economic status, were least likely to expect holistic care or empowerment. Two-thirds of patients also judged doctors on whether they performed an adequate physical examination, and three-quarters on the later outcomes of consultation (in terms of relief or cure and/or side-effects of prescribed drugs).

Conclusion

These findings suggest that Chinese patients in Hong Kong value engaged, empathic primary care doctors and judge the quality of consultations largely on these human skills and the attitudes and values that underpin them, as well as on the perceived outcomes of treatment. The match between themes relating to consultation process and the CARE Measure items suggests utility of this measure in this population, but further quantitative validation is required.