Acute and Chronic Erysipelothrix rhusiopathiae Infection in Lambs.

Polyarthritis caused by Erysipelothrix rhusiopathiae is a relatively common infection in lambs characterized by low mortality and high morbidity. E. rhusiopathiae is a ubiquitous Gram-positive bacterium that is both a commensal and a pathogen of vertebrates. The disease was studied during an outbreak in a Norwegian Spæl sheep flock. In the acute phase, 48 of 230 (20%) lambs developed clinical signs and 4 died (1.7%). One acute case was necropsied and E. rhusiopathiae was cultured from all major organs investigated and from joints. There was a fibrinous polyarthritis, increased presence of monocytes in vessels, and necrosis of Purkinje cells. Sixteen of the diseased animals (33%) developed a chronic polyarthritis. Eight of these lambs were necropsied; all had lesions in major limb joints, and 3 of 8 also had lesions in the atlanto-occipital joint. At this stage, E. rhusiopathiae was cultured only from the joints in 7 of 8 (87.5%) lambs, but by real-time polymerase chain reaction, we showed persistence of the bacterium in several organs. Pulsed-field gel electrophoresis typing of the bacterial isolates indicated that the same strain caused the acute and chronic disease. Five of 6 (83%) chronically affected animals had amyloidosis of the spleen, and 6 of 8 (75%) had amyloidosis of the liver. All chronically affected animals had a glomerulonephritis, and 6 of 8 (75%) had sparse degeneration in the brain. Ceruloplasmin and haptoglobin were significantly increased in the chronically diseased lambs. These results show that chronic ovine erysipelas is not restricted to joints but is a multisystemic disease.

Bovine respiratory syncytial virus: infection dynamics within and between herds.

The infection dynamics of bovine respiratory syncytial virus (BRSV) were studied in randomly selected Norwegian dairy herds. A total of 134 herds were tested twice, six months apart. The herds were classified as positive for BRSV if at least one animal between 150 and 365 days old tested positive for antibodies against BRSV, thereby representing herds that had most likely had the virus present during the previous year. The prevalence of positive herds at the first and second sampling was 34 per cent and at 41 per cent, respectively, but varied greatly between regions. Negative herds were found in close proximity to positive herds. Some of these herds remained negative despite several new infections nearby. Of the herds initially being negative, 42 per cent changed status to positive during the six months. This occurred at the same rate during summer as winter, but a higher rate of animals in the herds was positive if it took place during winter. Of the herds initially being positive, 33 per cent changed to negative. This indicates that an effective strategy to lower the prevalence and the impact of BRSV could be to employ close surveillance and place a high biosecurity focus on the negative herds.

Inflammatory response to therapeutic gold bead implantation in canine hip joint osteoarthritis.

Inflammatory changes associated with periarticular pure gold bead implants were studied in dogs involved in a clinical trial investigating motor dysfunction and chronic pain owing to hip joint dysplasia and osteoarthritis. Gold beads were percutaneously implanted via a needle into different locations surrounding the greater trochanter of the femur. Nine dogs with implants were necropsied. In all examined animals, characteristic histologic lesions were observed in the tissue surrounding the gold implants--namely, a fibrous capsule composed of concentric fibroblasts intermixed with a variable number of inflammatory cells and a paucicellular innermost layer of collagen with a few fibrocyte-like cells in empty lacunae. Lymphocytes dominated the inflammatory infiltrate, with rarely observed macrophages present in close proximity to the implant site. No giant cells were observed. Immunohistochemistry showed mixed populations of lymphocytes, both CD3 positive (T cells) and CD79a positive (B cells), which in some cases formed lymphoid follicles. Diffuse inflammatory changes were present to a minor extent in the perimysium and surrounding fascia. The inflammation observed in dogs is similar to that observed with gold implants in humans. It is possible that the clinically beneficial effect of gold beads for chronic osteoarthritis depends on sustained localized inflammation with localized release of soluble mediators. The encapsulation of the implant by a paucicellular and poorly vascularized fibrous capsule may help prevent an exaggerated inflammatory reaction by sequestering the gold bead from the surrounding tissue.

Enteropathogens and risk factors for diarrhea in Norwegian dairy calves.

The aims of the current study were to estimate the prevalence of enteropathogens in calves in Norwegian dairy herds, evaluate the clinical consequences of protozoal infections, and identify risk factors for diarrhea. The 135 participating herds were randomly selected from those in The Norwegian Dairy Herd Recording System that had at least 15 cow-years. Each herd was followed for 1 yr. Fecal samples from calves with (n = 68) or without (n = 691) diarrhea were analyzed for the presence of Cryptosporidium, Giardia, and Eimeria species. Diarrheic samples (n = 191) were assayed for rotavirus group A, bovine coronavirus (BCoV), Cryptosporidium, and Escherichia coli F5 by antigen ELISA. Blood samples (n = 1,348) were analyzed for antibodies against BCoV and rotavirus. Potential risk factors for diarrhea were analyzed by using Cox regression analysis adjusted for herd frailty effect. Rotavirus and Cryptosporidium were the most commonly detected enteropathogens in diarrheic samples. A high level of Cryptosporidium shedding or BCoV seropositive calves in a herd was associated with an increased risk of diarrhea. Other factors found to increase the risk of diarrhea were use of slatted concrete floor in group pens versus other floor types [hazard ratio (HR) = 8.9], housing of calves in free-stalls compared with tie-stalls (HR = 3.7), purchasing of calves into the herd versus not purchasing calves (HR = 4.1), and calves being born during winter compared with other seasons of the year (HR = 1.5).

Respiratory infections in Norwegian dairy calves.

The aims of this study were to estimate the seroprevalence of respiratory agents in Norwegian dairy calves and to identify risk factors for respiratory disease. The participating 135 herds were randomly selected from those in The Norwegian Dairy Herd Recording System with at least 15 cow years. Each herd was followed for 1 yr. Blood samples from calves of >150 d of age (n = 1,348) were analyzed for antibodies against parainfluenza virus 3, bovine coronavirus (BCoV), bovine respiratory syncytial virus (BRSV), and Mycoplasma bovis. Calves reported to have been on pasture (n = 139) were tested for antibodies against Dictyocaulus viviparus. Seroprevalences for parainfluenza virus 3, BCoV, BRSV, and D. viviparus at the calf level were 50.2, 39.3, 31.2, and 4.3%, respectively. No calves were antibody positive for M. bovis. Calves in herds with BCoV-seropositive calves had an increased risk of respiratory disease compared with herds in which BCoV antibodies were not detected [hazard ratio (HR) = 3.9], as had calves in herds in which the majority (>54%) of the sampled calves were seropositive for BRSV (HR = 2.7). Other factors found to increase the risk of respiratory disease in calves were shared housing with cows during the first week of life compared with separate housing (HR = 16.7), a larger herd size (>50 cow years) compared with smaller herds (HR = 8.2), more than an 8-wk age difference between calves housed together in the same group pen compared with having pen mates of a more similar age (HR = 3.9), previous recordings of diarrhea compared with no recorded diarrhea (HR = 3.9), and leaving calves with dams for >24 h after birth compared with earlier separation (HR = 3.5).

Calf mortality in Norwegian dairy herds.

The aims of this study were to estimate mortality rates in Norwegian dairy calves and young stock up to 1 yr of age, identify risk factors for calf mortality, and evaluate the etiology of calf mortality based on postmortem analyses. The material comprised 3 data sets. The first data set included information on 289,038 offspring in 14,474 dairy herds registered in the Norwegian Dairy Herd Recording System (NDHRS) in 2005. The second included recordings on 5,382 offspring in 125 Norwegian dairy herds participating in a survey on calf health, and the third included results from postmortem analyses of 65 calves from 37 of the survey herds. The calf mortality rate during the first year of life in all herds registered in the NDHRS was 7.8%, including abortion (0.7%) and stillbirth (3.4%). The overall calf mortality rate in liveborn calves in the survey herds was 4.6%. Cows with severe calving difficulties had an odds ratio (OR) of 38.7 of stillbirth compared with cows with no calving difficulties. Twins and triplets showed an increased risk of stillbirth compared with singletons (OR = 4.2 and 46.3, respectively), as did calves born in free stalls compared with tie stalls (OR = 1.9). Respiratory disease increased the risk of death in all age groups with hazard ratios (HR) of 6.4, 6.5, 7.4, and 5.6 during the first week of life, 8 to 30 d of age, 31 to 180 d of age, and 181 to 365 d of age, respectively. Diarrhea increased the risk of death among calves younger than 180 d of age, but the influence was only significant during the first week of life and between 8 to 31 d of age (HR = 2.4 and 2.9, respectively). Calves born during the winter were more likely to die during the first week of life than calves born during the summer (OR = 1.2), and were more likely to die during the first month of life than calves born during the autumn (OR = 1.2). Calf mortality rates in all age groups increased with increasing herd size. Calves housed in a group pen from 2 wk of age were more likely to die during the first month of life than calves housed individually (HR = 1.5). Bronchopneumonia and enteritis were the most frequent postmortem diagnoses, with proportional rates of 27.7 and 15.4%, respectively.

Calf health monitoring in Norwegian dairy herds.

The aims of this study were to estimate the incidence of calf diseases in Norwegian dairy herds, improve calf health recordings in the Norwegian Cattle Health Recording System (NCHRS), and investigate different methods for validation of calf health data. A longitudinal, cross-sectional survey of calf health in Norway was performed between September 1, 2004, and January 31, 2007. The participating dairy herds were randomly selected from among herds registered in the Norwegian Dairy Herd Recording System as having at least 15 cow-years. Each herd participated for 1 yr. Diseases and treatments of calves of up to 180 d of age in 135 dairy herds were reported using the NCHRS. In total, 6,668 calves were born in the participating dairy herds during the project period. A total of 573 (29.6%) of the 1,936 calf health recordings reported were recordings of diseases and 1,363 (70.4%) were events of preventive therapy, dehorning, or castration. The recorded incidence of diarrhea and respiratory disease was 3.8% and 2.9%, respectively. The median age of occurrence of diarrhea and respiratory disease was 17 and 37 d, respectively. Three different methods, based on sampling of diseased calves, dehorning as an indicator of a well-functioning recording system, or feedback on degree of commitment to calf health recording, were tested to assess validation of the calf health records. The 3 methods indicated an underestimation of calf health records in the NCHRS of approximately 40% and an estimated "true" incidence of diarrhea and respiratory disease of 5.5 and 4.1%, respectively. The results from this study demonstrate the importance of encouraging farmers to conduct calf health recordings. They also indicate that finding a standardized method for validation of health data is a considerable challenge.

Risk factors associated with colostrum quality in Norwegian dairy cows.

The objectives of the present study were to evaluate colostrum quality in Norwegian dairy cows based on IgG content, and to identify associations between possible risk factors and low colostral IgG. A longitudinal cross-sectional survey on calf health in Norway was performed between June 2004 and December 2006. The participating dairy herds were randomly selected among herds registered in the Norwegian Dairy Herd Recording System as having at least 15 cow years. The participating farmers were requested to sample 10 mL of colostrum from the first milking after calving from 12 cows that had calved during the defined project period of 365 d. Colostrum samples from 1,250 cows from 119 herds were collected. The material consisted of 451, 337, 213, and 249 samples collected from cows in their first, second, third, and fourth parity or more, respectively. Analysis was performed on IgG content by using single radial immunodiffusion. Mixed models with herd as a cluster were fit by using grams of IgG per liter of colostrum as the dependent variable for the statistical analyses. The IgG content in the colostrum sampled ranged from 4 to 235 g/L, with a median of 45.0 g of IgG/L, with the 10th, 25th, 75th, and 90th percentiles being 23.1, 31.4, 63.6, and 91.6 g of IgG/L, respectively. Altogether, 57.8% of the samples contained less than the desired 50 g of IgG/L of colostrum. Cows in their fourth parity or more were found to have significantly higher levels of IgG per liter of colostrum than cows in their first or second parity. Colostrum from cows in their second parity had the lowest level of IgG. Cows calving during the winter months (December, January, and February) produced colostrum with a significantly lower IgG content compared with cows calving in any other season of the year. Somatic cell count, measured after calving, was significantly higher in cows producing colostrum of inferior quality compared with those producing high-quality colostrum. Of the total variation in colostrum quality, 13.7% could be explained by cluster effects within herd. The variation in IgG content in colostrum produced by Norwegian dairy cows indicates a need for improved colostrum quality control and subsequent adjustment of the colostrum feeding regimen to ensure a protective immunological status for newborn calves.

Differentiation of the follicle-associated epithelium in ileal Peyer's patch and production of 50-nm particles are maintained in B-cell-depleted fetal sheep.

To evaluate the dependence of the differentiation of the follicle-associated epithelium (FAE) on the presence of follicular B-cells, the FAE of ileal Peyer's patch follicles was examined in B-cell-depleted fetal lambs. The FAE of these rudimentary follicles, which are devoid of lymphocytes, showed normal differentiation, including carbonic anhydrase reactivity and ultrastructural characteristics of transcytosis, extensive interdigitation of the lateral plasma membrane and the shedding of membrane-bounded particles, approximately 50 nm in size, resembling exosomes. These 50-nm membrane-bounded particles were abundant in the extracellular space of the epithelium and the dome but no particles were found in the rudimentary follicles. This study confirms that the rudimentary follicles consist of clusters of follicular dendritic cells. Our findings suggest that the differentiation of FAE of ileal Peyer's patch and the production of the 50-nm particles constitute features that appear to be independent of B-cells.

Validity of conjoint analysis to study clinical decision making in elderly patients with aortic stenosis.

OBJECTIVE: Written case simulations are increasingly being used to investigate clinical decision making. Our study was designed to determine the validity of written case simulations within a conjoint analysis approach. STUDY DESIGN AND SETTING: We developed a series of 32 written case simulations that differed with respect to nine clinical characteristics. These case simulations represented elderly patients with aortic stenosis. The clinical characteristics varied according to a fractional factorial design. We analyzed retrospectively all consecutive patients of 70 years of age or older with an aortic stenosis in three university hospitals. RESULTS: 34 cardiologists from three Dutch hospitals gave their treatment advice to each of these case simulations on a six-point scale (ranging from 'certainly no' to 'certainly yes' to surgical treatment). We compared the influence that the clinical characteristics had on the responses to these case simulations with their influence on the actual treatment decision for 147 actual patients in the same three hospitals. We found a strong agreement. This agreement was only slightly affected by the cut-off value used to dichotomize the treatment advice into a recommendation in favor of or against surgical treatment. CONCLUSION: Written case simulations reflect well how clinicians are influenced by specific clinical characteristics of their patients.

Continuously improving the practice of cardiology.

Guidelines for the management of patients with cardiovascular disease are designed to assist cardiologists and other physicians in their practice. Surveys are conducted to assess whether guidelines are followed in practice. The results of surveys on acute coronary syndromes, coronary revascularisation, secondary prevention, valvular heart disease and heart failure are presented. Comparing surveys conducted between 1995 and 2002, a gradual improvement in use of secondary preventive therapy is observed. Nevertheless, important deviations from established guidelines are noted, with a significant variation among different hospitals in the Netherlands and in other European countries. Measures for further improvement of clinical practice include more rapid treatment of patients with evolving myocardial infarction, more frequent use of clopidogrel and glycoprotein IIb/IIIa receptor blockers in patients with acute coronary syndromes, more frequent use of ß-blockers in patients with heart failure and more intense measures to encourage patients to stop smoking. Targets for the proportion of patients who might receive specific therapies are presented.

Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN).

AIMS: To evaluate the safety and efficacy of levosimendan in patients with left ventricular failure complicating acute myocardial infarction. METHODS AND RESULTS: Levosimendan at different doses (0.1-0.4 microg x kg(-1) x min(-1)) or placebo were administered intravenously for 6h to 504 patients in a randomised, placebo-controlled, double-blind study. The primary end-point was hypotension or myocardial ischaemia of clinical significance adjudicated by an independent Safety Committee. Secondary end-points included risk of death and worsening heart failure, symptoms of heart failure and all-cause mortality. The incidence of ischaemia and/or hypotension was similar in all treatment groups (P=0.319). A higher frequency of ischaemia and/or hypotension was only seen in the highest levosimendan dose group. Levosimendan-treated patients experienced lower risk of death and worsening heart failure than patients receiving placebo, during both the 6h infusion (2.0% vs 5.9%; P=0.033) and over 24h (4.0% vs 8.8%; P=0.044). Mortality was lower with levosimendan compared with placebo at 14 days (11.7% vs 19.6%; hazard ratio 0.56 [95% CI 0.33-0.95];P =0.031) and the reduction was maintained at the 180-day retrospective follow-up (22.6% vs 31.4%; 0.67 [0.45-1.00],P =0.053). CONCLUSION: s Levosimendan at doses 0.1-0.2 microg x kg(-1) x min(-1) did not induce hypotension or ischaemia and reduced the risk of worsening heart failure and death in patients with left ventricular failure complicating acute myocardial infarction.

Cardiac 123 I-MIBG imaging and clinical variables in risk stratification in patients with heart failure treated with beta blockers.

Both myocardial m-[123I]iodobenzylguanidine (123I-MIBG) uptake and plasma norepinephrine are markers of sympathetic activation in heart failure and have been shown to portend a poorer prognosis. However, these observations were noted before treatment with beta blockers became part of standard clinical practice. Fifty-eight patients with chronic heart failure (New York Heart Association functional class II and III, ejection fraction <35%; 53% ischaemic cardiomyopathy) were prospectively studied with a mean follow-up of 36 months. During the observational period, 17 patients (29.3%) had a predefined event (death and heart transplantation). All prognostic parameters were obtained before beta blocker therapy was initiated. In both uni- and multivariate analysis, the heart-mediastinum ratio of 123I-MIBG uptake did not correlate with cardiovascular mortality. In the multivariate Cox regression analysis, plasma norepinephrine, peak oxygen consumption, end-diastolic volume as measured by echocardiography and exercise performance during bicycling and walking had prognostic significance in patients with heart failure treated with beta blockers in addition to angiotensin-converting enzyme inhibitors.

Relationship between cardiac metaiodobenzylguanidine uptake and hemodynamic, functional and neurohormonal parameters in patients with heart failure.

BACKGROUND: Sympathetic activation plays a pivotal role in heart failure attributing to the disease process and symptoms of the patient. Myocardial sympathetic activity can be visualized using radioiodinated metaiodobenzylguanidine 123I-MIBG, a structural analogue of norepinephrine (NE). AIM OF THE STUDY: We investigated whether a relation exists between myocardial MIBG uptake and different functional, hemodynamic and neurohormonal parameters in patients with chronic heart failure. METHODS AND RESULTS: The study comprised 52 patients with stable congestive heart failure functional class II or III and left ventricular ejection fractions of <35%. The heart/mediastinum ratio (H/M ratio) was calculated to quantify myocardial MIBG uptake. A significant correlation was found between peak oxygen consumption and maximal exercise duration as exercise parameters and H/M ratio of MIBG (R, respectively, 0.36 and 0.4, P<0.05). From all other measured parameters, only plasma NE showed a significant correlation with the H/M ratio of MIBG. CONCLUSION: Cardiac sympathetic activity, as measured by myocardial MIBG uptake, is correlated with peak exercise parameters.

Reversal of pathophysiologic changes with long-term lisinopril treatment in isolated systolic hypertension.

The purpose of this study was to evaluate in a prospective, double-blind, placebo-controlled study the effect of long-term (2-year) lisinopril treatment on cardiovascular end-organ damage in patients with previously untreated isolated systolic hypertension (ISH). All patients with ISH were derived from a population screening program. End-organ damage measurements, done initially and after 6 and 24 months of treatment, included measurements of aortic distensibility and echocardiographic left ventricular mass index (LVMI) and diastolic function. Blood pressure was measured by office and ambulatory measurements. Of the 97 subjects with ISH selected from the screening, 62 (30 lisinopril) completed the study according to protocol. Office blood pressure decreased in both groups, but ambulatory results significantly decreased with lisinopril-treatment only. Aortic distensibility increased significantly with lisinopril, as opposed to a decrease in placebo-treated subjects. The main effect of increased distensibility occurred between 6 and 24 months, whereas ambulatory blood pressure changed mainly in the first 6 months of treatment. LVMI decreased in both treatment groups, with a significantly higher reduction in lisinopril-treated subjects. Left ventricular diastolic function showed no significant changes in either group. The vascular pathophysiologic alterations of ISH-a decreased aortic distensibility-can be improved with long-term lisinopril treatment, whereas values deteriorate further in placebo-treated subjects. These results, in one of the first studies including subjects with previously untreated ISH only, indicate that lisinopril treatment might favorably influence the cardiovascular risk of ISH.

Variability in treatment advice for elderly patients with aortic stenosis: a nationwide survey in The Netherlands.

OBJECTIVE: To determine how the decisions of Dutch cardiologists on surgical treatment for aortic stenosis were influenced by the patient's age, cardiac signs and symptoms, and comorbidity; and to identify groups of cardiologists whose responses to these clinical characteristics were similar. DESIGN: A questionnaire was produced asking cardiologists to indicate on a six point scale whether they would advise cardiac surgery for each of 32 case vignettes describing 10 clinical characteristics. SETTING: Nationwide postal survey among all 530 cardiologists in the Netherlands. RESULTS: 52% of the cardiologists responded. There was wide variability in the cardiologists' advice for the individual case vignettes. Six groups of cardiologists explained 60% of the variance. The age of the patient was most important for 41% of the cardiologists; among these, 50% had a high and 50% a low inclination to advise surgery. A further 24% were influenced equally by the patient's age and by the severity of the aortic stenosis and its effect on left ventricular function; among these, 62% had a high and 38% a low inclination to advise surgery. Finally, 23% of the cardiologists were mainly influenced by the left ventricular function and 12% by the aortic valve area. The presence of comorbidity always played a minor role. CONCLUSIONS: There were systematic differences among groups of cardiologists in their inclination to advise aortic valve replacement for elderly patients, as well as in the way their advice was influenced by the patients' characteristics. These results indicate the need for prospective studies to identify the best treatment for elderly patients according to their clinical profile.

Beta blockers in heart failure haemodynamics, clinical effects and modes of action.

Treatment for heart failure may be directed at relieving symptoms and/or improving prognosis. One of the primary aims of research in heart failure is to alter the progressive decline in pump function and thereby improve prognosis. For many years, diuretics have been known as therapeutics in heart failure and they are very effective in symptom relief. Vasodilators and inotropes also have beneficial effects on symptom relief especially in the acute phase through changes in cardiac output, filling pressures and renal perfusion. However, although these treatments produce short-term relief, none have been shown to influence the disease process and thereby improve mortality. Indeed, many of these drugs may even lead to untoward long-term clinical outcomes as has been shown for example for milrinone and ibopamine. There is overwhelming evidence that drugs interfering with the neurohormonal activation in heart failure not only produce symptomatic relief but are also capable of attenuating disease progression with concomitant reductions in both morbidity and mortality. About a decade ago, convincing and large-scale evidence showed that ACE inhibitors produced favourable effects by antagonising the activated renin-angiotensin system. More recently, ß-blockers, which antagonise the activated sympathetic system, were shown to be beneficial in the long term in moderate severe heart failure in terms of significant improvements in both morbidity and mortality. The RALES study further amplified the concept that drugs that interact in the neurohormonal system have beneficial effects. In this study, spironolactone, a weak, potassium-sparing diuretic counteracting aldosterone showed a reduction in mortality in more severe forms of heart failure.