Dynamics of widespread foot-and-mouth disease virus serotypes A, O and Asia-1 in southern Asia: A Bayesian phylogenetic perspective.

Foot-and-mouth disease (FMD) is, arguably, the animal disease with the most devastating global economic impact owing in part, to the severe trade restrictions imposed upon affected countries and regions. South Asia is one of the regions where widespread lineages of the FMDV virus (FMDV) have emerged. Here, we performed an integrative phylogenetic analysis of all FMDV serotypes (A, O and Asia-1) circulating in southern Asia, including viral sequences collected until 2013. Our results describe the occurrence of FMD caused by different serotypes and lineages, focusing in the cycles where a specific lineage predominates within a region for a protracted period and then are rapidly or progressively replaced by an emergent or re-emergent strain that is introduced from an adjacent region. Transmission between the two main regions in southern Asia (the Indian subcontinent and the region comprised by Afghanistan, Iran and Pakistan) has been limited. Results of time divergence estimation of lineages that currently circulate in this region indicate that the most recent common ancestor of endemic lineages are: 1992 [1989-1995] for lineage O/PanAsia; 1997 [1995-1999] for PanAsia2; 2001 [1998-2004] for O/Ind2001; 2001 [2000-2002] for A/Iran-05; 1990 [1988-1991] for A/G-18 (G-VII); 2003 [2000-2006] for Asia-1 Sindh08 and 2002 [1999-2004] for Asia-1 G-VIII. We estimated the mean of the overall substitution rate of the VP1 coding region (substitution/site/year) for serotype O (5.95 × 10-3 ), serotype A (1.19 × 10-2 ) and serotype Asia-1 (3.08 × 10-3 ). The potential factors driving the lineage turnover are discussed. Our results provide insights into the ecological and evolutionary factors driving the emergence of FMDV.

Parasites as valuable stock markers for fisheries in Australasia, East Asia and the Pacific Islands.

Over 30 studies in Australasia, East Asia and the Pacific Islands region have collected and analysed parasite data to determine the ranges of individual fish, many leading to conclusions about stock delineation. Parasites used as biological tags have included both those known to have long residence times in the fish and those thought to be relatively transient. In many cases the parasitological conclusions have been supported by other methods especially analysis of the chemical constituents of otoliths, and to a lesser extent, genetic data. In analysing parasite data, authors have applied multiple different statistical methodologies, including summary statistics, and univariate and multivariate approaches. Recently, a growing number of researchers have found non-parametric methods, such as analysis of similarities and cluster analysis, to be valuable. Future studies into the residence times, life cycles and geographical distributions of parasites together with more robust analytical methods will yield much important information to clarify stock structures in the area.

Effect of coadministered fat on the tolerability, safety, and pharmacokinetic properties of dihydroartemisinin-piperaquine in Papua New Guinean children with uncomplicated malaria.

Coadministration of dihydroartemisinin-piperaquine (DHA-PQ) with fat may improve bioavailability and antimalarial efficacy, but it might also increase toxicity. There have been no studies of these potential effects in the pediatric age group. The tolerability, safety, efficacy, and pharmacokinetics of DHA-PQ administered with or without 8.5 g fat were investigated in 30 Papua New Guinean children aged 5 to 10 years diagnosed with uncomplicated falciparum malaria. Three daily 2.5:11.5-mg-base/kg doses were given with water (n = 14, group A) or milk (n = 16, group B), with regular clinical/laboratory assessment and blood sampling over 42 days. Plasma PQ was assayed by high-performance liquid chromatography with UV detection, and DHA was assayed using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models for PQ and DHA were developed using a population-based approach. DHA-PQ was generally well tolerated, and initial fever and parasite clearance were prompt. There were no differences in the areas under the concentration-time curve (AUC0-∞) for PQ (median, 41,906 versus 36,752 µg · h/liter in groups A and B, respectively; P = 0.24) or DHA (4,047 versus 4,190 µg · h/liter; P = 0.67). There were also no significant between-group differences in prolongation of the corrected electrocardiographic QT interval (QTc) initially during follow-up, but the QTc tended to be higher in group B children at 24 h (mean ± standard deviation [SD], 15 ± 10 versus 6 ± 15 ms(0.5) in group A, P = 0.067) and 168 h (10 ± 18 versus 1 ± 23 ms(0.5), P = 0.24) when plasma PQ concentrations were relatively low. A small amount of fat does not change the bioavailability of DHA-PQ in children, but a delayed persistent effect on ventricular repolarization cannot be excluded.

Parasites as indicators of movement and population connectivity of a non-diadromous, tropical estuarine teleost: king threadfin Polydactylus macrochir.

Temporal and spatial patterns in parasite assemblages were examined to evaluate the degree of movement and connectivity of post-recruitment life-history stages of a large, non-diadromous tropical estuarine teleost, king threadfin Polydactylus macrochir, collected from 18 locations across northern Australia. Ten parasites types (juvenile stages of two nematodes and seven cestodes, and adults of an acanthocephalan) were deemed to be suitable for use as biological tags, in that they were considered to have a long residence time in the fish, were relatively easy to find and were morphologically very different to each other which aided discrimination. Univariate and discriminant function analysis of these parasites revealed little difference in temporal replicates collected from five locations, suggesting that the parasite communities were stable over the timeframes explored. Univariate, discriminant function, and Bray-Curtis similarity analyses indicated significant spatial heterogeneity, with Bray-Curtis classification accuracies ranging from 55 to 100% for locations in north-western and northern Australia, 24 to 88% in the Gulf of Carpentaria, and 39 to 88% on the east coast of Queensland. Few differences were observed among locations separated by <200 km. The observed patterns of parasite infection are in agreement with concurrent studies of movement and connectivity of P. macrochir in that they indicate a complex population structure across northern Australia. These results should be considered when reviewing the management arrangements for this species.

Stock structure of blue threadfin Eleutheronema tetradactylum across northern Australia, as indicated by parasites.

The parasite fauna of the blue threadfin Eleutheronema tetradactylum, collected from 14 sites across northern Australia, was examined to evaluate the degree of movement and subsequent stock structure of the fish. Univariate and multivariate analysis of nine 'permanent' parasite species [the nematodes Anisakis (type I) and Terranova (type II), the cestodes Otobothrium australe, Pterobothrium pearsoni, Pterobothrium sp. A, Callitetrarhynchus gracilis, Parotobothrium balli and Nybelinia sp., and the acanthocephalan Pomphorhynchus sp.] demonstrated little similarity between sites, indicating limited mixing and therefore long-term separation of post-juvenile fish. As such, the effects of fishing are likely to be localized within the current administrative boundaries, implying little need for interstate co-operative management. Within each jurisdiction, management of E. tetradactylum populations, including the establishment of harvest strategies and fishery regulations, should be conducted in a way that recognizes the resident nature of the fish.

Inflammatory bowel disease. 1. Origins, presentation, and course.

The exact cause of inflammatory bowel disease remains undiscovered, but its destructive nature is clearly recognized. In this article, the authors summarize what is known about the pathogenesis and epidemiology of ulcerative colitis and Crohn's disease and how to distinguish between the two, both clinically and pathologically. They also describe disorders that may mimic inflammatory bowel disease. In part 2 of this article, beginning on page 86, the authors discuss some of the therapeutic options that are the commonly used as well as some that are investigational but show promise for patients with this chronic and relapsing disease.

Inflammatory bowel disease. 2. Current and future therapeutic options.

The exact source of interference with the normal protective immune response in patients with inflammatory bowel disease remains unclear. Infectious causes have been proposed, and the increased incidence among family members indicates genetic predisposition. No matter what the pathogenesis may be, the disease is chronic, recurrent, and destructive in many cases. Conventional therapy with 5-ASAs, corticosteroids, immunomodulating agents, methotrexate, and antibiotics often offers relief. However, adverse effects accompany long-term use of many of these agents, so follow-up is important. Much investigation of alternative methods is under way, and anecdotal as well as published experience suggests benefits in at least some patients. Because of the chronic nature of their condition, patients with inflammatory bowel disease often become quite sophisticated in their understanding of treatment methods. Therefore, they should be told of updates regarding new options for disease control. We recommend that patients be seen periodically by a gastroenterologist who has expertise in inflammatory bowel disease, even when the disease is quiescent. Our experience in observing these patients over time strongly supports use of some of the agents discussed in this article for prophylaxis against flares and chronic inflammation.

Inflammatory markers in bronchoalveolar lavage fluid of standardbred racehorses with inflammatory airway disease: response to interferon-alpha.

Protein and eicosanoid concentrations and procoagulant activity were determined in bronchoalveolar lavage fluid (BALF) from 32 Standardbred racehorses with inflammatory airway disease (IAD) and 6 control horses. Total protein, albumin and immunoglobulin G (IgG) concentrations were high (P < 0.05) in the BALF from horses with IAD, a finding consistent with exudation of plasma protein into the airway. Immunoglobulin A (IgA) concentrations also were increased (P < 0.05) which may signify local immunoglobulin production. Difference was not detected in prostaglandin E2 and 6-ketoprostaglandin F1 alpha concentrations in BALF of IAD-affected and control horses. Procoagulant activity was identified in the majority (66%) of BALF samples from IAD-affected horses and was not detected in control horses. Natural human interferon-alpha (nHulFN alpha) (placebo, 50, 150, or 450 units) was administered orally for 5 days to IAD-affected horses in a double-blind, randomised block design. Total protein, IgG, and IgA concentrations in BALF were reduced (P < 0.05) 8 days after administration of 50 u and 150 u nHuIFN alpha, and 15 days after administration of 50 u nHuIFN alpha. Procoagulant activity and albumin concentrations in BALF were lower 8 days after administration of 50 u nHuIFN alpha. Oral administration of low-dose nHuIFN alpha appeared to ameliorate these parameters of lower respiratory tract inflammation in Standardbred racehorses with IAD.

Lower respiratory tract disease.

Lower respiratory tract disease is an important source of poor performance and exercise intolerance in racehorses and middle-aged sport horses. Horses that perform high-intensity exercise are predisposed to development of infectious and noninfectious respiratory disease. Diagnostic aids for investigation of lower respiratory tract disease include thorough thoracic auscultation with rebreathing, endoscopic examination, bronchoalveolar lavage (BAL), and thoracic radiographic examination. The therapeutic approach for horses with lower respiratory tract diseases often can be directed by cytologic evaluation of BAL fluid. Conservative management techniques may reduce the risk or severity of respiratory disease in horses performing high-intensity exercise.

Necrotizing enterocolitis in horses: a retrospective study.

The clinical and clinicopathologic characteristics of fatal necrotizing enterocolitis were examined in 16 horses (age 4 months to 12 years). At initial presentation, 8 of 16 horses were pyrexic (median temperature, 38.4 degrees C; range, 33.8 to 40.6 degrees C); all 16 were tachycardic (median heart rate, 93 bpm, range, 66 to 138 bpm); 13 of 16 were tachypneic (median heart rate, 36 bpm, range, 16 to 80 bpm), dehydrated, and had discolored mucous membranes. All horses that were pyrexic were also tachycardic and tachypneic. PCV was high (> 45%) in 14 horses. Six horses were leukopenic (< 5,000 cells/microL); 12 were neutropenic (< 2,300 cells/microL), and 14 had > 100 band neutrophils/microL. Twelve horses were acidemic (pH < 7.37; range, 6.88 to 7.33) and the venous bicarbonate concentration was low (< 23 mEq/L) in 14 horses. Median anion gap in 16 horses was 31.5 mEq/L (> 15 mEq/L in 15 horses). Eleven of 16 horses were hyponatremic (< 137 mEq/L), 1 horse was hypernatremic (> 143 mEq/L), 3 were hypokalemic (< 3.2 mEq/L), 6 were hyperkalemic (> 4.5 mEq/L), and 14 were hypochloremic (< 98 mEq/L). Serum creatinine concentrations were high (> 1.4 mg/dL) in 15 horses. Abdominal fluid was examined in 12 horses 4 had total protein concentrations > 2.5 g/dL and 6 had nucleated cell counts > 5,000/ microL and < 10,000/microL; none had > 10,000/microL. Eight of 12 samples revealed a nondegenerate neutrophilia (> 50%). Abdominal fluid collected from 4 horses immediately before death was normal in 2 horses and indicative of suppurative inflammation in 2. All 8 horses tested had low or nonexistent serum immunofluorescent antibody titers to Ehrlichia risticii. Four of 16 horses had Salmonella spp isolated from feces or tissues. All 16 horses either died (5 of 16; 31%) or were euthanized because of a grave prognosis. Median time to death was 45.5 hours (range, 7 to 113 hours) from the time of admission. Death was preceded by severe abdominal pain in 14 horses. Fatal necrotizing enterocolitis of horses is characterized by a brief course, profound dehydration, electrolyte derangements, acid-base abnormalities, and terminally, severe abdominal pain. Abdominal fluid analysis was frequently not indicative of the severity of disease.

Clinical application of interferons in large animal medicine.

Interferons are efficacious therapeutic agents for treatment of several clinically important diseases in cattle and horses. In some instances, the therapeutic goal of IFN administration is prevention or clinical cure of acute viral infections. On the other hand, IFN may serve as adjunctive treatment to diminish clinical manifestations of disease and improve the quality of life. Oral administration of IFN alpha appears to be a safe and convenient route of administration, and the therapeutic benefit likely develops via unique mechanisms involving oropharyngeal-associated lymphoid tissue for dissemination and amplification of the pharmacologic response. At the time of this writing, IFN has not been approved by the USDA or the FDA for use in food-producing animals or horses.

Colonic luminal pressure in horses with strangulating and nonstrangulating obstruction of the large colon.

Colonic luminal pressure (median, range) measured during ventral midline celiotomy in 69 horses with strangulating obstruction (SO) of the large colon (SO; > or = 270 degrees large colon volvulus; 27 cm H2O: 2 to 80 cm H2O) was greater (P = .0023) than that measured in 37 horses with nonstrangulating obstruction (NSO) of the large colon (NSO; < or = 180 degrees volvulus or a nonstrangulating displacement; 18 cm H2O; 6 to 46 cm H2O). Sixty-five percent (45 of 69) of horses with SO and all horses with NSO survived. Survival analysis was restricted to 59 horses with large-colon SO that survived to hospital discharge or met the criteria specified for classification as nonsurvivors. Colonic luminal pressure in nonsurvivors (48.5 cm H2O; 34 to 80 cm H2O) was higher (P =.0001) than that measured in survivors (18 cm H2O; 2 to 50 cm H2O) of SO. From response operating characteristic curves, a luminal pressure of 38 cm H2O optimized the distribution of horses with SO into survivor and nonsurvivor groups. Sensitivity, specificity, and positive and negative predictive values for a colonic luminal pressure greater than 38 cm H2O in predicting nonsurvival were 0.89, 0.91, 0.72 and 0.97, respectively. Measurement of colonic luminal pressure may be useful for predicting survival in horses with colonic volvulus.

Changes in airway inflammatory cell populations in standardbred racehorses after interferon-alpha administration.

Natural human interferon-alpha (nHuIFN alpha) was administered to actively training Standardbred racehorses with inflammatory airway disease (IAD). Inflammatory airway disease was characterized by poor exercise performance and inflammation and exudate in the upper and lower airway. Placebo, 50, 150, or 450 units(U) of nHuIFN alpha was administered orally for 5 consecutive days to eight horses per treatment group in a double-blind, randomized block design. Response to nHuIFN alpha was monitored by semiquantitative endoscopic examination score and cytologic examination of bronchoalveolar lavage fluid (BALF) performed at baseline (Day 1), Day 8 and Day 15 after initiation of nHuIFN alpha administration. Neutrophil, macrophage, lymphocyte, and nucleated cell counts in BALF were lower (P < 0.05), compared with BALF cell counts in placebo-treated horses 8 days after administration of 50 U and 150 U nHuIFN alpha, and 15 days after administration of 50 U nHuIFN alpha. Neutrophil, lymphocyte and nucleated cell counts were lower than cell counts from placebo-treated horses, 8 days following administration of 450 U nHuIFN alpha. The proportion CD4-, CD5-, and CD8-positive lymphocytes in BALF was not affected by administration of nHuIFN alpha. Oral administration of low-dose nHuIFN alpha reduced inflammation of the lowest respiratory tract in Standardbred racehorses with IAD.

Metacarpal fracture associated with lymphosarcoma-induced osteolysis in a horse.

A 19-year-old Appaloosa gelding was reluctant to move. Radiography revealed diffuse, permeative lysis of the cortex and subchondral bone of the phalanges, third metacarpal bones, proximal sesamoid bones, radius, carpal bones, tibia, mandible, and nasal bones of the skull. A comminuted fracture of the distal aspect of the left third metacarpal bone was identified on a lateral to medial radiographic view of the left metacarpophalangeal joint. Histologic examination of the first phalanx, third metacarpal bone, and sternum revealed multifocal infiltrates of nodular lymphosarcoma in cortical and subchondral bone. Osteoclastic cavities were apparent in bone trabeculae contiguous with nodular foci of lymphosarcoma. Osteoclastic osteolysis was not evident at bone surfaces that were not directly adjacent to neoplastic cells. Although lymphosarcoma is the most frequent malignant neoplasia encountered in horses, diffuse neoplastic infiltration of cortical and subchondral bone of the appendicular and axial skeleton represents an unusual presentation of lymphosarcoma.

Cytologic evaluation of bronchoalveolar lavage fluid obtained from standardbred racehorses with inflammatory airway disease.

Cytologic examination of bronchoalveolar lavage fluid (BALF), including phenotypic analysis of lymphocytes, was performed on 32 Standardbreds with poor race performance and endoscopic examination findings characteristic of inflammatory airway disease (IAD). Nucleated cell counts in BALF from IAD-affected horses were higher than those in control horses; the cytologic profile of BALF in affected horses included mixed inflammation, characterized by mild neutrophilia, lymphocytosis, and monocytosis. Eosinophil and mast cell counts were not higher in the IAD-affected group, compared with those in the control group; however, 4 IAD-affected horses had marked eosinophilia (24.7 +/- 4.8% SEM) in BALF. Phenotypic analysis of lymphocytes in BALF obtained from IAD-affected horses revealed a low proportion of CD4-positive cells and B cells, compared with those in the control group; these findings may have been representative of a greater proportion of non-B, non-T cells (null cells) in horses with IAD. The cytologic profile of BALF obtained from horses with IAD differed from that in horses affected with chronic obstructive pulmonary disease, suggesting that the pathogenesis of inflammation in horses with IAD may differ from that of chronic obstructive pulmonary disease.

Systemic and colonic venous hemostatic alterations in horses during low-flow ischemia and reperfusion of the large colon.

Twenty-four horses were randomly allocated to 3 groups. All horses underwent a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls, group-2 horses underwent 6 hours of colonic ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline blood samples were collected, then low-flow colonic ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. All horses were monitored for 6 hours. Citrated systemic venous (SV) blood samples were collected from the main pulmonary artery, and colonic venous (CV) samples were collected from the colonic vein draining the ventral colon. Samples were collected at 0, and 2, 3, 3.25, 4, and 6 hours for determination of one-stage prothrombin time, activated partial thromboplastin time, antithrombin III activity, and fibrinogen concentration. Data were analyzed statistically, using two-way ANOVA for repeated measures, and post-hoc comparisons were made by use of Student Newman Keul's test. Statistical significance was set at P < 0.05. There were significant decreases in all hemostatic variables by 2 hours in SV and CV samples from horses of all 3 groups, but there were no differences among the 3 groups for any of these variables. These hemostatic alterations could have been secondary to a hypercoagulable state or to fluid therapy-induced hemodilution. Colonic ischemia-reperfusion was not the cause of these alterations because these alterations also were observed in the sham-operated control horses. Significant temporal alterations existed even after accounting for the hemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)

Examination of the equine patient with gastrointestinal emergency.

Clinical examination of the equine patient with acute abdominal pain should identify the affected body system and yield a provisional diagnosis. Determination of signalment, history, physical examination, and basic laboratory tests should assist in classification of the gastrointestinal disorder and direct the therapeutic plan. Determination of the definitive diagnosis of abdominal pain based on clinical examination is not crucial. For a successful outcome, efforts should be directed toward early recognition of the need for surgery and treatment of cardiovascular compromise in horses with severe gastrointestinal disease.

Thick beryllium target as an epithermal neutron source for neutron capture therapy.

Accelerator-based intense epithermal neutron sources for Neutron Capture Therapy (NCT) have been considered as an alternative to nuclear reactors. Lithium (Li) has generally received the widest attention for this application, since the threshold energy is low and neutron yield is high. Because of the poor thermal and chemical properties of Li and the need for heat removal in the target, the design of Li targets has been quite difficult. Beryllium (Be) has been thought of as an alternative target because of its good thermal and chemical properties and reasonable neutron yield. However, in order to have a neutron yield comparable to that of a thick Li target bombarded with 2.5 MeV protons, the proton energy required for a thick Be target must be approaching 4 MeV. Consequently, the neutrons emitted are more energetic. In addition, a significant amount of high-energy gamma rays, which is undesirable, will occur when Be is bombarded with low-energy protons. Regardless of the more energetic neutrons and additional gamma rays, in this paper it is shown that it is possible to develop a high-quality and high-intensity epithermal neutron beam based on a thick Be target for NCT treatment. For a fixed proton current, the optimal Be-target-based beam (with 4-MeV protons) can produce a neutron beam, with both quality and intensity slightly better than those produced by the optimal Li-target-based beam (with 2.5-MeV protons). The single-session NCT treatment time for the optimal Be-target-based beam is estimated to be 88 min for a proton current of 50 mA.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperlipemia in 9 miniature horses and miniature donkeys.

The medical records from 9 consecutive miniature horses (n = 5) and miniature donkeys (n = 4) with hyperlipemia (serum triglyceride concentration > 500 mg/dL) were reviewed. In all cases, hyperlipemia was a secondary complication of a primary systemic disease including septicemia, colitis, parasitism, esophageal obstruction, gastric impaction and rupture, fecalith, and pituitary adenoma. Therapy consisted of specific treatment for the primary disease, supportive care, and nutritional support. The mean time for resolution of hyperlipemia in cases requiring nutritional support (n = 6) was 7 days, and the duration of nutritional support in surviving patients was 11.7 days. Seven of 9 patients survived. The primary disease resulted in death in 2 patients. Enteral feeding with commercially prepared low residue diets and treatment of the primary disease was successful in reversing hyperlipemia in 5 of 6 surviving patients that required nutritional support. Parenteral administration of a glucose-based (non-lipid) solution was successful in resolving hyperlipemia in 1 patient.

Heparin: a review of its pharmacology and therapeutic use in horses.

Heparin is used clinically in horses to treat hemostatic abnormalities associated with severe gastrointestinal disease, septicemia, and endotoxemia. The primary anticoagulant effect of heparin is through the suppression of thrombin-dependent amplification of the coagulation cascade, and inhibition of thrombin-mediated conversion of fibrinogen to fibrin. Heparin may be of benefit in preventing the complications associated with hypercoagulable states such as jugular vein thrombosis, laminitis, and organ failure. Heparin may also be beneficial in the prevention of intraabdominal adhesions after gastrointestinal surgery, and in amelioration of hemodynamic abnormalities associated with endotoxic shock. Because a sequential rise in serum heparin concentration occurs during a uniform dosage regimen, a decreasing dosage regimen is recommended. The initial dose recommended is 150 U heparin/kg body weight subcutaneously, followed by 125 U heparin/kg body weight subcutaneously, every 12 hours for six doses. The dose should be decreased to 100 U heparin/kg body weight subcutaneously, every 12 hours, after the seventh dose. Anemia, hemorrhage, thrombocytopenia, and painful swelling at injection sites are complications of heparin administration in horses.