Dynamic visualization of thrombopoiesis within bone marrow

Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis.     

A clinical comparison of remifentanil or alfentanil in propofol-anesthetized cats undergoing ovariohysterectomy

Sixteen cats were used to compare the cardiovascular and anesthetic effects of remifentanil (REMI) or alfentanil (ALF) in propofol-anesthetized cats undergoing ovariohysterectomy. After premedication with acepromazine, anesthesia was induced and maintained with a constant rate infusion of propofol (0.3 mg/kg/min). REMI or ALF infusions were administered simultaneously with propofol. Heart rate (HR), systolic arterial pressure (SAP), pulse oximetry (SpO(2)), rectal temperature (RT), and response to surgical stimulation were recorded at predefined time points during anesthesia. Data [mean±standard deviation (SD)] were analyzed by analysis of variance (ANOVA) for repeated measures followed by a Dunnett's test and Student t-test (P<0.05). SAP was significantly lower in ALF group than in REMI group. Extubation time was significantly shorter in REMI than in ALF group. Overall infusion rate of REMI and ALF was 0.24±0.05 μg/kg/min and 0.97±0.22 μg/kg/min, respectively. The combination of propofol and REMI or ALF provided satisfactory anesthesia in cats undergoing ovariohysterectomy.     

Geographical distribution of Alzheimer's disease cases at birth and the geochemical profile of Saguenay-Lac-Saint-Jean/Québec,Canada (image project)

Accepting as founded the hypothesis of a multifactorial origin for the Alzheimer's disease (AD), we explore the possible links between the geographical distribution of AD cases according to their birth place and the geochemical profile of the Saguenay-Lac-Saint-Jean (SLSJ) territory in the province of Québec. The method used for factor analysis of correspondances (FAC) and another one based on the differences between the residential and municipal geochemical concentrations (DRMC) have been used for this purpose. The geochemical matrix of SLSJ relates the highest concentrations of nickel, copper and zinc to the sector surrounding the Jonquière municipality. Moreover, high concentrations of iron, lead and manganese were found in the northern sector of the Lac Saint-Jean. The DRMC method corroborates this strong correlation between iron, lead and manganese. Furthermore, these concentrations do not differ from the north-american geochemical standards. No single geochemical element seems to be associate with the spatial distribution of cases. It is, however, still possible that a certain synergistic effect between two or several elements could be implied in the development of the disease. According to the results of the soil analysis, there does not seem to be any association between the spatial distribution of cases and the concentration of aluminum, a chemical element that has been thought to be implied in the etiology of AD. These results are compared with those obtained by other workers in the micronesian islands, where abnormally high frequencies of amyotrophic lateral sclerosis and parkinsonism dementia have already been observed.     

Tilmicosin-induced bovine neutrophil apoptosis is cell-specific and downregulates spontaneous LTB4 synthesis without increasing Fas expression

The pathology of bacterial pneumonia, such as seen in the bovine lung infected with Mannheimia haemolytica, is due to pathogen virulence factors and to inflammation initiated by the host. Tilmicosin is a macrolide effective in treating bacterial pneumonia and recent findings suggest that this antibiotic may provide anti-inflammatory benefits by inducing polymorphonuclear neutrophilic leukocyte (PMN) apoptosis. Using an in vitro bovine system, we examined the cell-specificity of tilmicosin, characterized the changes in spontaneous leukotriene B4 (LTB4) synthesis by PMN exposed to the macrolide, and assessed its effects on PMN Fas expression. Previous findings demonstrated that tilmicosin is able to induce PMN apoptosis. These results were confirmed in this study by the Annexin-V staining of externalized phosphatidylserine and the analysis with flow cytometry. The cell-specificity of tilmicosin was assessed by quantification of apoptosis in bovine PMN, mononuclear leukocytes, monocyte-derived macrophages, endothelial cells, epithelial cells, and fibroblasts cultured with the macrolide. The effect of tilmicosin on spontaneous LTB4 production by PMN was evaluated via an enzyme-linked immunosorbent assay. Finally, the mechanisms of tilmicosin-induced PMN apoptosis were examined by assessing the effects of tilmicosin on surface Fas expression on PMN. Tilmicosin-induced apoptosis was found to be at least partially cell-specific, as PMN were the only cell type tested to die via apoptosis in response to incubation with tilmicosin. PMN incubated with tilmicosin under conditions that induce apoptosis spontaneously produced less LTB4, but did not exhibit altered Fas expression. In conclusion, tilmicosin-induced apoptosis is specific to PMN, inhibits spontaneous LTB4 production, and occurs through a pathway independent of Fas upregulation.     

Comparison of perioperative racemic methadone, levo-methadone and dextromoramide in cats using indicators of post-operative pain

OBJECTIVE: To compare three opioid agonist drugs for perioperative analgesia in cats. STUDY DESIGN: Prospective, blind, controlled, randomised trial. ANIMALS: Ninety client-owned cats, weighing 3.1 (2.1-4.5) kg, aged 14.6 (6.0-84.0) months, were studied. METHODS: Seventy-six cats, scheduled for ovariectomy, received either 0.6 mg kg(-1) racemic methadone, 0.3 mg kg(-1) levo-methadone, 0.05 mg kg(-1) dextromoramide or a saline placebo IM. Behaviour and body position were assessed and scored 20 minutes later by a single 'blinded' observer. Anaesthesia was induced with propofol and maintained with halothane. Heart rate (HR), respiratory rate (RR), Fe'CO2 and SpO2 were recorded during anaesthesia. Post-operatively, pain was categorised as absent, moderate or severe, on the basis of appearance, behaviour and response to palpation of the surgical wound (pain score). Appearance, pain scores and physiological variables were monitored every 30 minutes, for a duration of 4 hours. Differences between time-dependent continuous variables were analysed using mixed models for repeated measurements. Differences in categorical, time-dependent variables were analysed using chi2-tests. Significance was set at p < or = 0.05. RESULTS: There were no significant changes in appearance after pre-anaesthetic medication. After surgery, there was no association between appearance and pain score with HR or RR. The assessment of pain depended on comparison with the placebo group, by comparing animals' reactions to wound palpation. Sixteen of the 18 cats in the placebo group and 14 of the 19 cats in the dextromoramide group showed signs of moderate-to-severe pain after surgery. In the levo-methadone group (n = 20), one animal showed pain after 60 minutes and two after 120 minutes. One cat in the racemic methadone group (n = 19) showed pain signs and behavioural changes at 60 minutes. Compared to the two methadone groups, 'rescue' analgesia was required more often in cats treated with dextromoramide or saline. CONCLUSION AND CLINICAL RELEVANCE: Dextromoramide (0.05 mg kg(-1)) was ineffective, while racemic methadone (0.6 mg kg(-1)) and levo-methadone (0.3 mg kg(-1)) provided effective analgesia in cats following ovariectomy, without behavioural, respiratory or cardiovascular side effects.     

West Nile virus-associated mortality events in domestic Chukar partridges (Alectoris chukar) and domestic Impeyan pheasants (Lophophorus impeyanus)

West Nile virus (WNV) infection was diagnosed in captive juvenile chukars (Alectoris chukar), and captive juvenile Impeyan pheasants (Lophophorus impeyanus) on the basis of necropsy, histopathology, polymerase chain reaction, and immunohistochemistry. The chukars were kept in a game bird farm that experienced two outbreaks with approximately 25% mortality in hundreds of chukars between September and October 2002 and during the same months in 2003. The submitted pheasants were part of a group of 15 juvenile Impeyan pheasants that all died within approximately 2 wk at the end of August 2002. The macroscopic lesions in the pheasants were dominated by mucosal hemorrhage at the proventricular to ventricular junction and cecal ulcers, whereas the gross lesions in the chukar partridges were nonspecific. The predominant microscopic lesion in the chukar partridges was myocardial necrosis, whereas fibrinous and necrotizing splenitis was prominent in the pheasants. Viral antigen was usually widespread in animals of both species. Spontaneously occurring WNV infection should be considered a differential diagnosis in cases of mortality among select species of galliform birds.     

Food insecurity, malnutrition and mortality in Maewo and Ambae Islands, Vanuatu

CONTEXT: This paper reports on findings from the ex-post evaluation of the Maewo Capacity Building project in Maewo Island, Vanuatu, which was funded by World Vision Australia. OBJECTIVES: To examine the extent to which the infrastructure and systems left behind by the project contributed to the improvement of household food security and health and nutritional outcomes in Maewo Island, using Ambae Island as a comparator. SETTING: Two-stage cluster survey conducted from 6 to 20 July 2004, which included anthropometric measures and 4.5-year retrospective mortality data collection. PARTICIPANTS: A total of 406 households in Maewo comprising 1623 people and 411 households in Ambae comprising 1799 people. MAIN OUTCOME MEASURES: Household food insecurity, crude mortality rate (CMR), under-five mortality rate (U5MR) and malnutrition prevalence among children. RESULTS: The prevalence of food insecurity without hunger was estimated at 15.3% (95% confidence interval (CI): 12.1, 19.2%) in Maewo versus 38.2% (95% CI: 33.6, 43.0%) in Ambae, while food insecurity with hunger in children did not vary by location. After controlling for the child's age and gender, children in Maewo had higher weight-for-age and height-for-age Z-scores than children of the same age in Ambae. The CMR was lower in Maewo (CMR = 0.47/10 000 per day, 95% CI: 0.39, 0.55) than in Ambae (CMR=0.59/10 000 per day, 95% CI: 0.51, 0.67) but no difference existed in U5MR. The major causes of death were similar in both locations, with frequently reported causes being malaria, acute respiratory infection and diarrhoeal disease. CONCLUSIONS: Project initiatives in Maewo Island have reduced the risks of mortality and malnutrition. Using a cross-sectional 'external control group' design, this paper demonstrates that it is possible to draw conclusions about project effectiveness where baseline data are incomplete or absent. Shifting from donor-driven evaluations to impact evaluations has greater learning value for the organisation, and greater value when reporting back to the beneficiaries about project impact and transformational development in their community. Public health nutritionists working in the field are well versed in the collection and interpretation of anthropometric data for evaluation of nutritional interventions such as emergency feeding programmes. These same skills can be used to conduct impact evaluations, even some time after project completion, and elucidate lessons to be learned and shared. These skills can also be applied more widely to projects which impact on the longer-term nutritional status of communities and their food security.