The effects of anagrelide on human megakaryocytopoiesis

Anagrelide, an inhibitor of platelet aggregation, decreases the number of platelets in normal subjects and in patients with myeloproliferative disorders. We describe studies aimed at discovering the general mechanism(s) by which anagrelide acts. We examined three hypotheses: (1) anagrelide shortens platelet survival, (2) anagrelide inhibits the proliferation of megakaryocytic-committed progenitor cells (CFU-M), and (3) anagrelide inhibits maturation of megakaryocytes. We observed that anagrelide did not shorten platelet survival. Proliferation of CFU-M in vivo was not affected by anagrelide, although high concentrations of anagrelide inhibited CFU-M in vitro . In-vivo and in-vitro anagrelide altered the maturation of megakaryocytes, causing a decrease in their size and changing other morphometric features. We conclude that anagrelide decreases the number of platelets primarily by interfering with the maturation of megakaryocytes.     

ESC Study Group of Sports Cardiology: recommendations for participation in leisure-time physical activity and competitive sports for patients with ischaemic heart disease.

BACKGROUND: Evidence for the proper management of ischemic heart disease (IHD) in the general population is well established, but recommendations for physical activity and competitive sports in these patients are scarce. The aim of the present paper was to provide such recommendations to complement existing ESC and international guidelines on rehabilitation and primary/secondary prevention. DESIGN AND METHODS: Due to the lack of studies in this field, the current recommendations are the result of consensus among experts. Sports are classified into low/moderate/high dynamic and low/moderate/high static, respectively. RESULTS: Patients with a definitive IHD and higher probability of cardiac events are not eligible for competitive sports (CS) but for individually designed leisure time physical activity (LPA); patients with definitive IHD and lower probability of cardiac events as well as those with no IHD but with a positive exercise test and high risk profile (SCORE > 5%) are eligible for low/moderate static and low dynamic (IA-IIA) sports and individually designed LPA. Patients without IHD and a high risk profile+ a negative exercise-test and those with a low risk profile (SCORE < 5%) are allowed all LPA and competitive sports with a few exceptions. CONCLUSIONS: Individually designed LPA is possible and encouraged in patients with and without established IHD. Competitive sports may be restricted for patients with IHD, depending on the probability of cardiac events and the demands of the sport according to the current classification.     

Effect of norfloxacin on human oropharyngeal and colonic microflora and multiple-dose pharmacokinetics

10 healthy volunteers received 200 mg norfloxacin orally every 12 h for 7 days. Saliva, throat and faecal specimens were collected days 0, 3, 5, 7, 14 and 21 to study the effect of norfloxacin on the normal microflora. The concentrations of norfloxacin in serum, urine, saliva and faeces were determined by a microbiological method and all samples except faeces were also assayed by high-pressure liquid chromatography (HPLC). The pharmacokinetics of norfloxacin were studied on day 3. The mean peak serum concentration (+/- SD) attained after 0.75-1.0 h was 0.75 +/- 0.15 mg/l measured by HPLC, and the mean terminal serum half-life was 4.2 +/- 0.6 h. The mean cumulative urinary elimination was 29% during 12 h after dosing. There was no significant difference between values obtained by microbiological assay and by HPLC. The saliva concentration was approximately 30% of the serum levels 1.0-1.5 h after administration. No accumulation in faeces was found during the administration period, and mean concentrations were 940 mg/kg. The changes in the oropharyngeal flora were minor and only branhamella were affected. In the colonic flora, the number of enterobacteria was strongly depressed while the anaerobic microflora was only slightly affected. Two weeks after the administration period, both the oropharyngeal and colonic microflora had returned to normal.     

Broad consent versus dynamic consent in biobank research: Is passive participation an ethical problem?

In the endeavour of biobank research there is dispute concerning what type of consent and which form of donor–biobank relationship meet high ethical standards. Up until now, a ‘broad consent'' model has been used in many present-day biobank projects. However it has been, by some scholars, deemed as a pragmatic, and not an acceptable ethical solution. Calls for change have been made on the basis of avoidance of paternalism, intentions to fulfil the principle of autonomy, wish for increased user participation, a questioning of the role of experts and ideas advocating reduction of top–down governance. Recently, an approach termed ‘dynamic consent'' has been proposed to meet such challenges. Dynamic consent uses modern communication strategies to inform, involve, offer choices and last but not the least obtain consent for every research projects based on biobank resources. At first glance dynamic consent seems appealing, and we have identified six claims of superiority of this model; claims pertaining to autonomy, information, increased engagement, control, social robustness and reciprocity. However, after closer examination, there seems to be several weaknesses with a dynamic consent approach; among others the risk of inviting people into the therapeutic misconception as well as individualizing the ethical review of research projects. When comparing the two models, broad consent still holds and can be deemed a good ethical solution for longitudinal biobank research. Nevertheless, there is potential for improvement in the broad model, and criticism can be met by adapting some of the modern communication strategies proposed in the dynamic consent approach.     

Gastric mucosa lesions induced by duodenogastric reflux increase penetration of N-[3H]-methyl-N-nitro-N-nitrosoguanidine into corpus mucosa of rats

The mucosal changes by which duodenogastric reflux may predispose to gastric cancer have not been fully clarified. In this study in rats, duodenal fluid was directed into the stomach through a gastroenterostomy (jejunal reflux, N = 29) or through the pylorus (pyloric reflux, N = 30) and compared with 30 controls. Twenty-four weeks later the stomach was exposed to N-[³H]methyl-N-nitro-N-nitrosoguanidine ([³H]MNNG). The corpus mucosa was examined for proliferating cells (bromodeoxyuridine labeled) and cells at risk of methyl-N-nitro-N-nitrosoguanidine-induced carcinogenesis (cells labeled with bromodeoxyuridine and [³H]MNNG). The number of double-labeled cells increased from 0.8 ± 0.1/mm mucosa in the control group to 5.2 ± 0.9 in the jejunal reflux group (P < 0.05) and 2.7 ± 0.5 in the pyloric reflux group (P < 0.05). An erosion or ulcer appeared at the gastroenterostomy in 52% of animals with jejunal reflux and 17% of those with pyloric reflux (P < 0.006). Within erosions the mean number of double-labeled cells was 9.6 ± 2.2 in the jejunal reflux group and 7.7 ± 4.8 in the pyloric reflux group, and significantly higher than in the nonlesion area of the mucosa (0.6 ± 0.2 and 0.8 ± 0.3). In erosions the distance between the gastric lumen and the proliferating cells was significantly shorter and the cell proliferation significantly higher than in the nonlesion area of the mucosa. We conclude that duodenogastric reflux increases the penetration of [³H]MNNG into the corpus mucosa of rats and also induces mucosa lesions, which further increase the penetration of [³H]MNNG into the corpus mucosa.     

Geriatric Care Boot Camp: An Interprofessional Education Program for Healthcare Professionals

In response to the need for interprofessional geriatrics education, a half‐day geriatric care boot camp for healthcare professionals was held that covered core concepts in geriatric medicine: delirium and dementia, medication management, palliative care, ethics, and a general overview of older adults. Aspects of the curriculum focused on interprofessional education, and the attendees and presenters were healthcare professionals from a wide variety of fields. Primary objectives were to determine changes in knowledge of core concepts in geriatrics and level of comfort in caring for older adults. Secondary objectives assessed whether participants found the interprofessional approach beneficial and whether they used or shared this information with others in their professional activities. Participants completed pre‐ and postassessment surveys. Changes in participant understanding of each core concept were statistically significant, as was the change in comfort level of participants in caring for older adults. Furthermore, attendees found the multidisciplinary perspective of the boot camp beneficial. A 3‐month follow‐up survey assessed whether attendees applied and shared information learned in their own professional activities. Half of the respondents who reported sharing universally shared core concepts. Delirium and dementia information was most frequently shared. Information was most frequently shared with students, nurses, and patients’ families. Attendees less frequently shared, or did not share, with physicians, physician assistants, social workers, physical and occupational therapists, nutritionists, and dentists. The healthcare professionals who may benefit greatly from future education programs are those with whom the boot camp information was least frequently shared; thus, they are appropriate targets for advertisements for future programs.