Magnetic resonance microscopy of the equine hoof wall: a study of resolution and potential.

REASONS FOR PERFORMING STUDY: Obtaining magnetic resonance images of the inner hoof wall tissue at the microscopic level would enable early accurate diagnosis of laminitis and therefore more effective therapy. OBJECTIVES: To optimise magnetic resonance imaging (MRI) parameters in order to obtain the highest possible resolution of the structures beneath the equine hoof wall. METHODS: Magnetic resonance microscopy (MRM) was performed in front feet from 6 cadaver horses using T2-weighted fast spin echo (FSE-T2), and T1-weighted gradient echo (GRE-T1) sequences. RESULTS: In T2 weighted FSE images most of the stratum medium showed no signal, however the coronary, terminal and sole papillae were visible. The stratum lamellatum was clearly visible and primary epidermal lamellae could be differentiated from dermal lamellae. CONCLUSION: Most structures beneath the hoof wall were differentiated. Conventional scanners for diagnostic MRI in horses are low or high field. However this study used ultra-high field scanners currently not available for clinical use. Signal-to-noise ratio (S/N) increases as a function of field strength. An increase of spatial resolution of the image results in a decreased S/N. S/N can also be improved with better coils and the resolution of high field MRI scanners will increase as technology develops and surface array coils become more readily available. POTENTIAL RELEVANCE: Although MR images with microscopic resolution were obtained ex vivo, this study demonstrates the potential for detection of lamellar pathology as it occurs. Early recognition of the development of laminitis to instigate effective therapy at an earlier stage and may improve the outcome for laminitic horses. Clinical MR is now readily available at 3 T, while 4 T, 7 T and 9 T systems are being used for human whole body applications.

Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells.

DNA methyltransferase 3A (DNMT3A) mutations are observed in myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Transplantation studies have elucidated an important role for Dnmt3a in stem cell self-renewal and in myeloid differentiation. Here, we investigated the impact of conditional hematopoietic Dnmt3a loss on disease phenotype in primary mice. Mx1-Cre-mediated Dnmt3a ablation led to the development of a lethal, fully penetrant MPN with myelodysplasia (MDS/MPN) characterized by peripheral cytopenias and by marked, progressive hepatomegaly. We detected expanded stem/progenitor populations in the liver of Dnmt3a-ablated mice. The MDS/MPN induced by Dnmt3a ablation was transplantable, including the marked hepatomegaly. Homing studies showed that Dnmt3a-deleted bone marrow cells preferentially migrated to the liver. Gene expression and DNA methylation analyses of progenitor cell populations identified differential regulation of hematopoietic regulatory pathways, including fetal liver hematopoiesis transcriptional programs. These data demonstrate that Dnmt3a ablation in the hematopoietic system leads to myeloid transformation in vivo, with cell-autonomous aberrant tissue tropism and marked extramedullary hematopoiesis (EMH) with liver involvement. Hence, in addition to the established role of Dnmt3a in regulating self-renewal, Dnmt3a regulates tissue tropism and limits myeloid progenitor expansion in vivo.

Nuclear magnetic resonance-based metabonomic study of early time point laminitis in an oligofructose-overload model.

REASONS FOR PERFORMING STUDY: NMR-metabonomics is an unbiased evaluation method, which allows to comprehensively study changes of the equine metabolic profile in early time point laminitis. This might give insight into the early stages of disease development. OBJECTIVES: To detect hitherto unknown changes in blood metabolites during the development of oligofructose-induced laminitis by comparing pre- and post induction blood samples. METHODS: Prior to laminitis induction blood was sampled to establish control values. Post oligofructose administration (POA) blood was collected every 3 h for 24 h. One-dimensional (1) H-NMR spectra of the blood plasma were statistically analysed. RESULTS: NMR resonances of >20 metabolites were identified using this technique. Already known changes (e.g. lactate concentrations) were confirmed using this method. Interestingly, oligofructose, a carbohydrate usually considered indigestible in the small intestine, or derivatives of oligofructose, was detected in plasma. Horses also showed increased phosphatidylcholine and/or low density lipoprotein levels POA, indicating a change in blood lipid composition. An increase in phosphatidylcholine is consistent with the breakdown of the mucosal layer of the large intestine and increased permeability of the gut. CONCLUSION: Due to the nontargeted approach of metabonomics, new unexpected changes can be identified, in this case the hitherto unknown oligofructose uptake through the mucosal wall and the phospholipid changes. POTENTIAL RELEVANCE: Metabolic changes in disease can be observed using NMR metabonomics. Oligofructose is used in feedstuffs and transport mechanisms through the mucosa should be studied. Phospholipids could point to a compromise of the intestinal wall during laminitis development.

The effect of natural killer cell killer Ig-like receptor alloreactivity on the outcome of bone marrow stem cell transplantation for severe combined immunodeficiency (SCID).

Natural killer (NK) cell alloreactions against recipient cells in the setting of bone marrow transplantation have been associated with decreased rates of graft-versus-host disease (GVHD) and improved survival in transplant recipients with myeloid leukemia. These alloreactions are predicted by the absence of recipient HLA class I ligands for donor inhibitory killer Ig-like receptors (KIR). We hypothesized that donor NK cell alloreactions against recipient cells may affect the development of T and B-cell functions and incidence of GVHD in infants with severe combined immunodeficiency (SCID). Of the 156 patients with SCID who had received related bone marrow transplants without pretransplant chemotherapy or posttransplant GVHD prophylaxis, 137 patient-donor pairs were evaluated for the absence of recipient HLA class I ligands for donor inhibitory KIR. Analysis showed that the absence of a KIR ligand had no effect on the incidence or severity of GVHD (RR [corrected] = 0.95, p = 0.84), development of T-cell function (RR [corrected] = 1.05, p = 0.69), production of IgA (p = 0.46) or IgM (p = 0.33), or on 5-year survival (RR [corrected] = 1.21, p = 0.10). Further, in patients possessing native NK cells, the absence of KIR ligands in donors for recipient-inhibitory KIR did not alter transplantation outcomes. This study suggests that inhibitory KIR/HLA interactions do not play a significant role in bone marrow transplantation for SCID.

Quality assurance. A new role for the hospital epidemiologist.

Quality assurance may be viewed as a method for the surveillance of healthcare provided in hospitals and other settings. The processes involved in quality assurance are in many ways analogous to the concepts and techniques that comprise the discipline of epidemiology. As yet, there has been little interaction between these specialty areas, and the lack of recognition of their relevance to one another is exemplified by the fact that hospital epidemiologists are rarely called upon to assist in the planning and operation of quality assurance programs. This loss of opportunity may be remedied by the inclusion of quality assurance methodology in the training of epidemiologists, and the introduction of certain epidemiologic concepts and methods into the quality assurance curricula. The intersection of these two disciplines will enlarge the scope of both and foster advances in theory and practice in this field.

Evaluation of protocol change in burn-care management using the Cox proportional hazards model with time-dependent covariates.

Survival analysis methods are valuable for detecting intervention effects because detailed information from patient records and sensitive outcome measures are used. The burn unit at a large university hospital replaced routine bathing with total body bathing using chlorhexidine gluconate for antimicrobial effect. A Cox proportional hazards model was used to analyse time from admission until either infection with Staphylococcus aureus or discharge for 155 patients, controlling for burn severity and two time-dependent covariates: days until first wound excision and days until first administration of prophylactic antibiotics. The risk of infection was 55 per cent higher in the historical control group, although not statistically significant. There was also some indication that early wound excision may be important as an infection-control measure for burn patients.

Pathology of atherosclerotic heart disease in sudden death. I. Organizing thrombosis and acute coronary vessel lesions.

The significance of organizing thrombosis was investigated in 121 cases of sudden death with atherosclerotic heart disease. Organizing thrombosis was observed in one-third of the cases, and sites at which it was present showed a higher prevalence of acute lesions -- thrombus, plaque rupture, and hemorrhage -- than sites at which it was not present. Acute and subacute coronary lesions were almost entirely restricted to vessels with 75% or greater obstruction. Evidence was presented suggesting that the organization of thrombosis in the coronary arteries was a more extended process than that observed in peripheral arteries.

Pathology of atherosclerotic heart disease in sudden death. II. The significance of myocardial infarction.

The role of myocardial infarction was investigated in 121 cases of sudden death with atherosclerotic heart disease. In addition to supporting other reports which have demonstrated the importance of chronic occlusion of the coronary vessels in relation to the high rate of infarctions found in such cases, the authors presented evidence which showed differences in occurrence in the sites of remote and recent infarctions, a lack of concordance between the sites of recent infarctions, and acute thrombosis in coronary vessels proximal to these lesions. No relationship between patient age or prior symptoms could be associated with the occurrence of infarction. Evidence was also presented which discounted the possible role of transmural infarction in the formation of acute thrombosis. These pathological observations support the concept that sudden cardiac deaths are results of functional instability of the myocardium produced by advanced coronary atherosclerosis.

Differences in pulmonary function tests among whites, blacks, and American Indians in a textile company.

Normal standards for pulmonary function in nonwhite populations are not presently available to occupational health workers. The present study examined differences in %FVC, FVC, FEV1/FVC, FEF 200-1200 and FEF 25-75% among whites, blacks, and American Indians. The sample consisted of 4209 job applicants to a textile company in southeastern United States. Multiple regression and analyses of covariance were employed to control differences in age, height, weight, and smoking status. Blacks were significantly lower in five of the six comparisons but higher in FEV1/FVC%. The pulmonary function measures of Indians fell generally between those of whites and blacks. Differences were observed between blacks and whites of both sexes regarding the effects of cigarette smoking. The need for race specific stardards was confirmed and the question of using smokers in the acquisition of normative data was raised.

Phagotrophy of fluorescently labeled bacteria by an oceanic phytoplankter.

Using fluorescently-labeled bacteria and detection by flow cytometry and epifluorescence microscopy, we demonstrate inducible mixotrophy in a marine photosynthetic flagellate, Ochromonas sp. (class Chrysophyceae). Phagotrophic uptake of bacteria increases under conditions of low or limiting light and nutrients, but deceases in periods of prolonged darkness; sustained phagotrophy may require light. In addition, this alga appears to discriminate between and preferentially ingest different types of bacteria. Although this clone is primarily photosynthetic, phagotrophy contributes to its nutrition, especially when light or nutrients limit photosynthesis.

Quality of life in nurse case management of persons with AIDS receiving home care.

Effects of case management on quality of life were tested with 57 home care patients with AIDS, randomly assigning individuals to either usual care or case-managed care over the duration of home services (ranging from 5 days to over 2 years). Participants were primarily male (93%), white (79%), and never married (82%). Quality of life was measured monthly using the quality of Well-Being Index (QWB). Case-managed patients showed advantages over the usual care group in descriptive analyses of quality of life and survival. Large standard deviations in the QWB scores resulting from high fatality among subjects impeded statistical analyses of effects.