Risk of thromboembolism and fatal stroke in patients with psoriasis and nonvalvular atrial fibrillation: a Danish nationwide cohort study.

OBJECTIVES: Psoriasis is a chronic inflammatory disease that is associated with a prothrombotic state and cardiovascular disease, including atrial fibrillation and thromboembolism. We therefore evaluated the impact of psoriasis in patients with atrial fibrillation and the performance of the CHA2 DS2 VASc score in these patients. DESIGN, SETTING AND PARTICIPANTS: The study comprised all Danish patients hospitalized with nonvalvular atrial fibrillation in the period 1997-2011 (n = 99,357). Follow-up started 7 days from discharge and excluded subjects treated with anticoagulation. Poisson regression adjusted for CHA2 DS2 VASc score was used to estimate the incidence rate ratios and 95% confidence intervals. MAIN OUTCOME MEASURE: Hospitalization or death from thromboembolism. RESULTS: Mean follow-up was 3.5, 3.1, and 2.8 years for patients with no psoriasis, mild psoriasis and severe psoriasis, respectively. Patients with psoriasis were younger compared to patients without psoriasis, but CHA2DS2VASc score did not differ between the three groups. Thromboembolism rates per 100 patient-years (95% confidence intervals) were 4.8 (4.7-4.9), 4.8 (4.2-5.4) and 6.1 (5.0-7.5) for patients with no psoriasis, mild psoriasis and severe psoriasis, respectively. Importantly, the observed thromboembolism rates in patients with severe psoriasis were markedly higher (2.6- to3.4-fold) than predicted by the CHA2 DS2 VASc score. Relative to no psoriasis, incidence rate ratios were 0.99 (0.87-1.11) and 1.27 (1.02-1.57) for mild and severe psoriasis, respectively. Correspondingly, incidence rate ratios for fatal stroke were 0.97 (0.80-1.12) and 1.51 (1.12-2.05). CONCLUSIONS: In patients with nonvalvular atrial fibrillation not treated with oral anticoagulation, severe psoriasis was associated with increased risk of thromboembolism. In these patients, CHA2 DS2 VASc underestimated the risk of thromboembolism.

Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes.

OBJECTIVE: In a previous study, urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy controls. Urinary orosomucoid was measured using a particle-enhanced immunoturbidimetric assay. Plasma interleukin-6 (IL-6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule-1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity of the brachial artery and echocardiography were done in all participants. RESULTS: Patients with diabetes and increased UOER had subclinically increased serum orosomucoid (p<0.001), C-reactive protein (CRP) (p<0.001), IL-6 (p<0.001), tPA (p<0.003) and sICAM (p<0.003) compared with healthy controls. In patients with type 2 diabetes, UOER was independently associated with increasing values of IL-6 (1.43 (1.06-1.93)) and tPA (1.82 (1.20-2.77)). Measurements by echocardiography showed no signs of cardiac dysfunction. CONCLUSIONS: Asymptomatic patients with type 2 diabetes and increased UOER displayed signs of chronic low-grade inflammation and endothelial dysfunction. UOER was independently related to markers of proinflammation and endothelial dysfunction in patients with type 2 diabetes. The previously shown relation between increased UOER and cardiovascular mortality is proposed to be caused by chronic low-grade inflammation and early endothelial dysfunction.

Persistent infection of turkeys with an avirulent strain of turkey hemorrhagic enteritis virus.

The Virginia avirulent strain (VAS) of turkey hemorrhagic enteritis virus (THEV), which is commonly used in live vaccines for commercial turkeys, was studied to determine characteristics of infection. It has been observed that turkeys infected with the VAS maintain protective antibody levels in excess of 20 wk postvaccination. It is theorized that this immune response is modulated by either a persistent or latent infection. A series of studies have been undertaken to determine changes in virus location and serology over time. A trial was also conducted to evaluate the effect of corticosteroid administration on viral recrudescence, and an attempt was made to isolate live virus from tissues of birds 10 wk postinfection (pi). Antibody titers were determined by enzyme-linked immunosorbent assay, and PCR was used to detect viral DNA. Histopathology was performed on formalin-fixed paraffinized tissues. Viral DNA was detected in various tissues through 15 wk pi in the presence of high antibody titers. Viral DNA was detected at 3-5 days pi in the spleens of susceptible turkeys inoculated with tissues collected from infected birds at 10 wk pi. It is unknown whether the viral DNA is associated with live virus or rather is the result of persistent maintenance of the viral genome within lymphoid/macrophage target cells. Future studies will test for viral RNA in order to confirm the presence of replicating THEV. Regardless of the actual status of the THEV DNA detected at 10-15 wk pi, it is clear that THEV does not cause a simple acute infection. The characteristics of THEV infection are identical to the nonlytic persistent infections seen in human adenoviruses, and therefore THEV may serve as a model for the study of virus-cell interactions mediating persistence.

Viability and function in lymphocytes cultured from the horse, chicken, and mouse: effects of different leukocyte enrichment techniques.

Methods of lymphocyte enrichment tend to vary across species, with the most common techniques employed being density-gradient separation and erythrocyte lysis buffer enrichment. In this study, we assessed lymphocyte viability and proliferation of avian, equine, and murine lymphocytes enriched by a commercial density-gradient technique and under identical, standardized culture conditions. The results of this study clearly show that, under identical enrichment and culture conditions, lymphocyte viability and function can be quite different among the equine, bird, and mouse species. Secondly, the type of enrichment technique employed in the mouse can impact the quality of the immune data generated.

Dihydroergotamine and mobilization after major orthopedic surgery.

The effects of dihydroergotamine (DHE) on the degree of mobilization and response to orthostatic stress after total hip arthroplasty were studied. In the mobilization study, 78 patients received DHE, 0.5 mg im, twice a day from the day of surgery until full mobilization was achieved. Eighty-four patients who received placebo served as controls. There was no significant difference in the time until the first day of mobilization or the degree of mobilization. In the orthostatic test condition, subgroups of 61 patients receiving placebo and 55 patients receiving DHE were subjected to orthostatic testing. There were no differences in cardiovascular response to bed rest or in orthostatic stress. We conclude that DHE does not stabilize the cardiovascular reaction to orthostatic stress, nor does it enhance mobilization in patients after total hip arthroplasty.

The effect of stress on the response of chickens to coccidiosis vaccination.

Six-week-old Leghorn chickens, which had been adapted to both their environment and cage mates, were orally inoculated with 400 Eimeria tenella oocysts as a means of low-dose vaccination. At 2, 3, 4, 5 or 6 days after vaccine administration, the birds were subject to 24 h of social stress through a prescribed method of random redistribution. Two weeks after vaccine administration, the birds were challenged by oral inoculation with 8000 oocysts. Caecal lesion scores were determined 6 days after challenge. Vaccinated chickens were more resistant to lesion formation than unvaccinated controls, and protection, as determined by lower lesion scores, was significantly enhanced when stress in the form of social disruption was applied on the fourth day following vaccine administration.

Experimental Cochlosoma anatis infections in poultry.

Cochlosoma anatis [Kotlán, A., 1923. Zentralbl. Bakteriol. Parasitenkd. Infektienskr. Hyg. 90, pp. 24-28] is a flagellated protozoan parasite of birds. We have encountered C. anatis in turkeys with enteritis. Experimental oral inoculations of turkeys with 1 x 10(6) to 10 x 10(6) trophozoites consistently reproduced infections in recipients. Trophozoites were most numerous in the jejunum and ileum but could be observed in the duodenum, ceca, colon, and feces. When 12 naive turkeys were placed on contaminated litter vacated by excreting turkeys only one of 12 became infected. When eight naive turkeys were placed in boxes with birds currently excreting trophozoites, seven of eight became infected. Trophozoites could not survive exposure to water or to freezing. Attempts to culture trophozoites in modified Diamond's medium, Kiester's medium, RPMI 1640 medium with 10% fetal bovine serum, or on cultured bovine turbinate cells were not successful. Four of six bobwhite quail and one of eight chickens orally inoculated with 10 x 10(6) to 20 x 10(6) trophozoites had detectable infections. Trophozoites were observed only in the ilea of bobwhite quail and the ceca of the positive chicken. Trophozoites collected from chickens and bobwhite quail remained infectious for turkeys.

The effectiveness of benzimidazole derivatives for the treatment and prevention of histomonosis (blackhead) in turkeys.

The benzimidazole derivatives, albendazole and fenbendazole were evaluated for their effectiveness in the treatment and prevention of histomonosis (blackhead) in turkeys. Histomonosis was produced in 5 week-old birds by placing them on broiler breeder litter known to be contaminated with Heterakis gallinae ova and the protozoan Histomonas meleagridis. In the first trial, at the onset of confirmed clinical disease, birds were treated orally with metronidazole, a compound known to be effective against Histomonas. Those receiving metronidazole had significantly greater mean body weight gains during the treatment period and the 2 weeks following treatment than untreated controls. Treated birds also had significantly lower caecal and liver lesion scores. These findings served to validate the method of disease reproduction and establish its suitability for testing the benzimidazoles. Similar trials were conducted to determine the therapeutic value of albendazole at 100.0 mg/kg of body weight and fenbendazole at 10.0 mg/kg body weight, administered orally twice a day for 5 consecutive days. Under these conditions, both drugs were found to be ineffective as treatments. A final trial was conducted to assess the prophylactic value of albendazole and fenbendazole administration. At the time of placement on contaminated litter, birds were medicated as previously described with the exception that treatment was continued for 14 consecutive days, the approximate incubation period for histomonosis. The trial was terminated on the 16th day. In the case of both albendazole and fenbendazole, treatment was associated with a significant increase in mean body weight gain and lower caecal and liver lesion scores. It is believed that the observed prophylactic effect may be attributed to the destruction of the transport vector e.g., Heterakis larvae, or to direct killing of the flagellated form of Histomonas which is normally found in the caecal lumen and is considered to be more sensitive to chemotherapeutic agents than the amoeboid form found in tissues.

The production of colibacillosis in turkeys following sequential exposure to Newcastle disease virus or Bordetella avium, avirulent hemorrhagic enteritis virus, and Escherichia coli.

Female large white turkeys were intranasally inoculated with either Newcastle disease virus (ND) or Bordetella avium (BA) at 4 weeks of age. This was followed by oral inoculation with an avirulent (vaccine) strain of hemorrhagic enteritis virus (HE) at 5 weeks and intravenous inoculation with Escherichia coli (EC) at 6 weeks. Control birds received ND, BA, or HE followed by EC; EC alone; or nothing at all. Turkeys receiving one agent prior to EC challenge did not experience a significant increase in mortality or pericarditis. Those exposed to ND or BA followed by HE and EC experienced a significant elevation in mortality and pericarditis. A highly significant positive correlation between the number of infectious agents encountered during primary exposure and the incidence of colibacillosis after EC challenge was demonstrated.

Analysis of avian lymphocyte proliferation by a new, simple, nonradioactive assay (lympho-pro).

An assessment of T-cell-mediated immune functions (i.e., lymphocyte proliferation assay) in the chicken, unlike the determination of antibody levels, is not routinely performed. This is primarily because of difficulties in the isolation of relatively pure populations of lymphocytes and the use of radioactive isotopes. To address these issues, the goals of our study were to optimize a method for isolating and enriching avian lymphocyte populations and to develop a nonradioactive lymphocyte proliferation assay. To accomplish these goals, we used a multiple slow-speed centrifugation technique combined with a "swirl" collection technique for lymphocyte isolation from chicken peripheral blood. After a fraction enriched with lymphocytes was obtained, a simple, rapid colorimetric and fluorometric assay (lympho-pro) to indirectly determine mitogen-induced proliferation was adapted and compared with the "Gold Standard" [3H]thymidine. Chickens of different ages and two genetic strains were used in this study. Lymphocytes were stimulated with various concentrations of concanavalin A (Con A, T-cell mitogen) or phorbol 12-myristate 13-acetate + ionomycin (pan lymphocyte mitogen). Our studies showed that the pattern of lymphocyte proliferation assessed by the Alamar blue-based lympho-pro assay was similar to the [3H]thymidine incorporation assay. Younger birds had higher levels of mitogen-induced proliferation when compared with adults of the same genetic strain. Because the lympho-pro assay, unlike [3H]thymidine, does not require lysis of cells to assess proliferation, cells that have undergone stimulation/proliferation can be subsequently characterized by staining with antibodies against cell surface antigens and analysis by flow cytometry. Another notable advantage of the lympho-pro assay is the rapidity of assessment and nontoxicity. In conclusion, this assay may be of value in assessing some aspects of T-cell-mediated immunity in both avian research and avian medicine diagnostic settings.

Field outbreaks of colibacillosis of turkeys associated with hemorrhagic enteritis virus.

In a study of field material and a survey conducted by the authors, typical signs of colibacillosis of 6-to-12-week-old poults included sudden onset, listlessness, rales, and high mortality. Signs persisted for about 2 weeks and were often followed by a low incidence of lameness caused by Escherichia coli. Gross lesions included enlarged and congested spleens and livers, and dilated discolored black or purple duodenal loops. Microscopic lesions included splenic and hepatic congestion. In some birds (freshly killed and fixed immediately), the epithelium at the tips of the duodenal villi was sloughing, but in other birds the villi were intact and normal in appearance. Splenic enlargement, the presence of intranuclear splenic inclusions similar to those found in hemorrhagic enteritis (HE), and the isolation of HE virus from some of the field spleens all indicated that inapparent HE infection often occurs at approximately the same time as this type of colibacillosis. It is therefore believed that HE infection often exacerbates colibacillosis of older poults.

Colibacillosis of turkeys exacerbated by hemorrhagic enteritis virus. Laboratory studies.

Lesions typical of colibacillosis disease were reproduced in laboratory experiments. Mortality resulting from experimentally produced colibacillosis was significantly increased when Escherichia coli O1:K1 was presented to poults that had been orally inoculated with hemorrhagic enteritis virus (HEV) 1 week earlier. These and previous data suggest that HEV infection can exacerbate colibacillosis of older poults. HEV infection apparently damages the poults' defense system enough to account for the observed increase in susceptibility to E. coli.

Ulcerative cholecystitis produced by 3-nitro-4-hydroxy-phenylarsonic acid toxicosis in turkey poults.

Naturally occurring ulcerative cholecystitis was present in a flock of 21-day-old turkey hens that were accidentally given at least 0.004% 3-nitro-4-hydroxy-phenylarsonic acid (3-NITRO) in their water for 2 days. Similar lesions were reproduced by administering 0.002% 3-NITRO to 2-day-old turkey poults for 6 days. Turkeys 31 days old were given up to 0.004% 3-NITRO in their water for 6 days, but no gall bladder ulcers were present in these poults. The toxicity to turkeys of 3-NITRO in the water appears to be age-dependent.

Effect of dietary selenium on the response of stressed and unstressed chickens to Escherichia coli challenge and antigen.

Selenium was added to the feed of White Leghorn type chickens 1 day prior to challenge with either Escherichia coli or sheep erythrocyte antigen. The incidence of death or lesions was reduced from 86% to 21% at the optimal dose of selenium (0.4 mg/kg resulting in feed concentration of 0.45 mg/kg). After the chickens were stressed by chilling, selenium was ineffective against E. coli. Dietary additions of selenium between 0.1 and 0.8 mg/kg resulted in an antibody titer increase from 2.2 to 3.9 to the log2 against sheep erythrocytes (SRBC). Following chilling, antibody titer response was reduced from 4.9 to 2.4 to the log2. This titer reduction could be prevented with dietary additions of selenium between 0.1 and 1.2 mg/kg. The effects of a nitrofuran and selenium were additive against E. coli challenge infection.

Effect of halothane, isoflurane, and pentobarbital anesthesia on myocardial irritability in chickens.

The relative myocardial irritant properties of halothane, isoflurane, and pentobarbital were evaluated in chickens. Sixteen adult male broiler chickens were randomly assigned to 1 of 3 groups: group-1 chickens were anesthetized with pentobarbital (30 mg/kg, IV), group-2 chickens were anesthetized with halothane (end tidal halothane 1.2%), and group-3 chickens were anesthetized with isoflurane (end tidal isoflurane 2.1%). Birds in any 2 of the 3 treatment groups were tested on any 1 day. Local anesthesia was induced, and blood pressure, heart rate, ECG, and blood gas variables were measured before general anesthesia was induced. Positive-pressure ventilation with an inspired O2 fraction greater than 0.95 was adjusted to result in an end tidal CO2 concentration that reflected a Paco2 similar to that obtained prior to anesthesia and ventilation. All measurements were repeated. The threshold for ventricular fibrillation in response to electrical stimulation of the heart was then determined for all birds. Effects of anesthesia on hemodynamic and blood gas variables were similar in all 3 groups. Compared with halothane or pentobarbital, isoflurane anesthesia resulted in a significantly (P less than 0.05) lower threshold for electrical fibrillation of the heart.

Immunity to transmissible (coronaviral) enteritis of turkeys (bluecomb).

Turkey flocks recovering from natural and laboratory induced coronaviral enteritis developed lifelong immunity. Virus neutralization tests indicated that neutralization capacity of serums from recovered turkeys was low. One-way cross challenge test using turkeys inoculated with various bluecomb isolates revealed close antigenic relationship or antigenic identity among bluecomb isolates. The controlled application of intestinal preparations containing coronavirus as a vaccination procedure had value in developing active lasting immunity but it has limitations in areas that are attempting to eliminate the disease by a depopulation program. Killed vaccines injected parenterally did not produce a detectable immunity.

Epizootiology of chronic wasting disease in free-ranging cervids in Colorado and Wyoming.

Surveillance and epidemic modeling were used to study chronic wasting disease (CWD), a transmissible spongiform encephalopathy that occurs naturally among sympatric, free-ranging deer (Odocoileus spp.) and Rocky Mountain elk (Cervus elaphus nelsoni) populations in contiguous portions of northeastern Colorado and southeastern Wyoming (USA). We used clinical case submissions to identify endemic areas, then used immunohistochemistry to detect CWD-infected individuals among 5,513 deer and elk sampled via geographically-focused random surveys. Estimated overall prevalence (prevalence, 95% confidence interval) in mule deer (4.9%, 4.1 to 5.7%) was higher than in white-tailed deer (2.1%, 0.5 to 3.4%) or elk (0.5%, 0.001 to 1%) in endemic areas; CWD was not detected in outlying portions of either state. Within species, CWD prevalence varied widely among biologically- or geographically-segregated subpopulations within the 38,137 km2 endemic area but appeared stable over a 3-yr period. The number of clinical CWD cases submitted from an area was a poor predictor of local CWD prevalence, and prevalence was typically > or =1% before clinical cases were first detected in most areas. Under plausible transmission assumptions that mimicked field data, prevalence in epidemic models reached about 1% in 15 to 20 yr and about 15% in 37 to 50 yr. Models forecast population declines once prevalence exceeded about 5%. Both field and model data supported the importance of lateral transmission in CWD dynamics. Based on prevalence, spatial distribution, and modeling, we suggest CWD has been occurring in northeastern Colorado and southeastern Wyoming for >30 yr, and may be best represented as an epizootic with a protracted time-scale.

Turkey poult tolerance to diets containing deoxynivalenol (vomitoxin) and salinomycin.

Feed taken from a commercial turkey farm where poults had refused to eat the feed and high mortality had occurred was analyzed and found to contain .81 mg/kg vomitoxin and 2.2 mg/kg salinomycin. The present four experiments investigated the effects of diets containing salinomycin at 0, 2.2, 5.5, 11, and 22 mg/kg and vomitoxin at 0, 2.2, and 4.4 mg/kg. A factorial design with vomitoxin at 0 and 4.4 mg/kg and salinomycin at 0 and 22 mg/kg was used in Experiment 4. Poults fed the suspect commercial diet had significantly lower feed consumption and higher motality than poults fed a control diet (P less than .05). Poults (0 to 3 wk of age) fed diets containing vomitoxin (4.4 mg/kg), salinomycin (22 mg/kg), or both showed no significant decrease in feed consumption, body weight gain, or viability.

Research note: resistance of chickens to an outbreak of necrotic enteritis as influenced by major histocompatibility genotype and background genome.

An outbreak of necrotic enteritis occurred in chickens that were B13B13 or B21B21 at the MHC in sublines of lines selected for high (HA) and low (LA) antibody response to sheep erythrocytes. Percentage mortality and hen-day egg production, although similar for both background genomes, were different for MHC genotypes. Mortality was 6% for B21B21 and 15% for B13B13 types. Although hen-day egg production for both types declined from about 76 to 50%, the decrease occurred earlier but recovery of survivors was faster in B13B13 than in B21B21 pullets.

Effect of oxytetracycline-hydrochloric acid on reproduction of female turkeys.

Effects of oxytetracycline-HCl on reproductive performance of turkey breeder hens from the 13 to 24-wk production period were evaluated. During the 13th wk of production, females were grouped into low, medium, and high fertility subclasses. Females within each fertility subclass were randomly reassigned to treatments. The antibiotic was administered via the drinking water (T-2) or via the drinking water plus an intravaginal lavage (T-3). Hens receiving T-2 treatment showed significantly higher fertility than untreated controls (T-1) but also showed significantly higher early embryonic mortality than those receiving the T-3 treatment. Hatchability of all egg set was significantly higher in both antibiotic-treated groups than in controls. Females in the fertility subclasses remained significantly different from each other throughout the experiment. To determine the duration of the effect of antibiotic treatment, eggs were collected in a treatment and posttreatment periods. Fertility (P less than .05), and hatchability (P less than .10) were improved during the treatment period compared with results of the posttreatment period. The T-3 treatment had a long-term effect: it maintained early embryonic mortality at 10% and hatchability at the same level during both treatment periods. A short-term effect was observed in the T-2 group; early embryonic mortality increased (P less than .05) and hatchability decreased (P less than .10) during the posttreatment period. No correlations were found between mycoplasmal or bacterial populations and fertility subclass or antibiotic treatment. Egg production, body weight, feed consumption, feed consumed per egg, egg weight, and egg specific gravity were unaffected by antibiotic treatment.