Across and within breed differences in the relationship between packed cell volume and fecal egg count in growing meat goat and hair sheep males naturally and artificially infected with gastrointestinal nematodes.

The relationship between packed cell volume (PCV) and fecal egg count (FEC) in different breeds of meat goats and hair sheep infected with gastrointestinal nematodes, including Haemonchus contortus, was characterized. Growing males from eight commercial and two research farms (one Kiko, Spanish, Dorper, and St. Croix; three Boer; four Katahdin) in the southcentral United States were evaluated in a central performance test with ad libitum intake of a 50% concentrate pelleted diet. There were 84 Boer, 55 Kiko, and 57 Spanish goats and 52 Dorper, 129 Katahdin, and 49 St. Croix sheep. During adaptation, animals were dewormed then dosed with 10,000 infective H. contortus larvae. PCV and FEC were determined before deworming (i.e., natural infection potentially with multiple internal parasites) and 21, 28, 35, 42, and 49 days after artificial infection. Effects of species, breed, and year were analyzed with mixed effects models including day of sampling post dosing as a repeated measure and FEC and FEC × breed as covariates. Moreover, differences in correlation coefficients between PCV and logarithmic FEC (lnFEC) among species, breed, year, and day of sampling were evaluated. Breed affected (P ≤ 0.001) PCV in goats (24.8, 27.2, and 26.0% for Boer, Kiko, and Spanish, respectively; SEM = 0.42) and sheep (29.8, 26.7, and 31.0% for Dorper, Katahdin, and St. Croix, respectively; SEM = 0.28). There were effects of FEC × breed (P ≤ 0.029) on PCV for Boer, Kiko, Dorper, Katahdin, and St. Croix (-0.31, -0.33, -0.46, -0.46, and - 0.49% per 1000 eggs, respectively) but not for Spanish goats (P = 0.451). With all data, PCV and lnFEC with natural infection were highly correlated (P < 0.001) for Boer and Kiko goats and Dorper and Katahdin sheep (r = -0.59, -0.67, -0.77, and - 0.84, respectively) but not for Spanish goats or St. Croix sheep (P ≥ 0.323). Correlation coefficients for artificial infection with H. contortus were significant (P ≤ 0.002) except for Spanish goats, although values were lower (-0.40, -0.21, -0.23, -0.47, and - 0.28 for Boer, Kiko, Dorper, Katahdin, and St. Croix, respectively) compared with natural infection. In conclusion, PCV was not related to FEC in Spanish goats infected either naturally or artificially, and the nature of the relationship varied among breeds of goats and sheep. Based on the magnitude of the FEC × breed coefficient, sheep incurred a relatively greater reduction in PCV as FEC increased, and correlation coefficients indicate stronger relationships with natural than artificial infection.

Effect of Ovar-DRA and Ovar-DRB1 genotype in small ruminants with haemonchosis.

The effect of Ovar-DRA and Ovar-DRB1 genotypes on faecal egg count (FEC) was determined in sheep and goats infected with Haemonchus contortus. One hundred and forty-three sheep from 3 different breeds (St. Croix, Katahdin and Dorper) and 150 goats from three different breeds (Spanish, Boer and Kiko) were used. Parasitological (FEC), haematological (packed cell volume) and immunological (IgA, IgG and IgM) parameters were measured. Sheep populations showed a higher FEC and humoural response than goat breeds. Genotypes were determined by high-resolution melting assays and by conventional PCR. For Ovar-DRA, sheep and goats carrying the AA genotype showed significant lower FEC than AG and GG genotypes. The additive effect was found to be 115.35 less eggs per gram of faeces for the A allele for goats. For Ovar-DRB1, only in sheep, the GC genotype was associated with low FEC. The additive effect was 316.48 less eggs per gram of faeces for the G allele, and the dominance effect was 538.70 less eggs per gram of faeces. The results indicate that single nucleotide polymorphisms within Ovar-DRA and Ovar-DRB1 could be potential markers to be used in selection programmes for improving resistance to Haemonchus contortus infection.

Early clinical experiences with nintedanib in three UK tertiary interstitial lung disease centres.

BACKGROUND: Nintedanib has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). It was approved by the National Institute for Health and Care Excellence (NICE) in January 2016 for IPF patients with a forced vital capacity (FVC) of 50-80% in the United Kingdom (UK). AIM: To report real world data about our early clinical experience using nintedanib in 187 patients with a multi-disciplinary (MDT) diagnosis of IPF in a manufacturer funded patient in need scheme (three UK centres) prior to NICE approval. METHODS: All patients with a MDT diagnosis of IPF from December 2014 to January 2016 commenced on nintedanib were included. Demographic details, adverse events (AEs) and where available lung function results were retrospectively collected from clinical letters. RESULTS: 187 patients (76% males) with a median age of 72 years (49-89) were treated with nintedanib. The average pre-treatment FVC was 81.1 ± 19.8% and diffusion capacity of the lungs for carbon monoxide was 43.9 ± 15% (n = 82). Fifty percent of patients started nintedanib because they were ineligible for pirfenidone due to an FVC > 80%. The median treatment course was 8 ± 4 months. The majority of patients experienced 1-3 AEs with nintedanib (52%, n = 97). The most frequent AEs were diarrhoea (50%), nausea (36%), reduced appetite (24%), tiredness (20%) and gastro-oesophageal reflux (18%). The majority of AEs resulted in no change in treatment (64%, n = 461). 21% (n = 150) of AEs resulted in a dose reduction and 13% (n = 94) necessitated discontinuation of treatment. 1 in 5 patients discontinued treatment either temporarily or on a permanent basis during the monitoring period. In a select cohort of patients, a statistically significant greater proportion of patients remained stable or improved and a lower proportion declined, as depicted by FVC changes of > 5% after nintedanib commencement (P < 0.05 using Chi squared test). CONCLUSIONS: Nintedanib is well tolerated and has an acceptable safety profile. Only 8% of those reporting diarrhoea discontinued treatment either on a temporary or permanent basis. There were no signals with respect to increased cardiovascular morbidity or major bleeding risk. This is in keeping with the INPULSIS clinical trial findings but in a real world cohort.

Haemophilus influenzae pneumonia and immunodeficiency in association with thymoma--a presentation of Good's syndrome.

INTRODUCTION: Good's Syndrome is a rare cause of immunodeficiency associated with thymoma. Patients with this syndrome are prone to infections with encapsulated microorganisms. The diagnosis may be delayed for a considerable time period even after the thymectomy. CASE PRESENTATION: We describe the case of a 70-year-old woman with a background of thymectomy who presented with pneumonia and gram negative sepsis. Haemophilus influenzae was found in blood cultures. Moreover, there was evidence of impaired B and T cell immunity consistent with Good's Syndrome. She was commenced on immunoglobulin replacement following treatment of sepsis and remains well 18 months after the initial presentation. CONCLUSION: This case illustrates the importance of considering Good's Syndrome in the context of pneumonia and immunodeficiency associated with encapsulated organisms such as Haemophilus influenzae. This clinical entity is associated with a significant mortality and should be considered as a cause of immunodeficiency even years after thymectomy.

Functional and clinical consequences of Fc receptor polymorphic and copy number variants.

Receptors for immunoglobulins (Fc receptors) play a central role during an immune response, as they mediate the specific recognition of antigens of almost infinite diversity by leucocytes, thereby linking the humoral and cellular components of immunity. Indeed, engagement of Fc receptors by immunoglobulins initiates a range of immunoregulatory processes that might also play a role in disease pathogenesis. In the circulation, five main types of immunoglobulins (Ig) exist - namely IgG, IgA, IgE, IgM and IgD and receptors with the ability to recognize and bind to IgG (Fc gamma receptor family), IgE (Fc epsilon RI and CD23), IgA (CD89; Fc alpha/microR) and IgM (Fc alpha/microR) have been identified and characterized. However, it is astonishing that nearly all the known human Fc receptors display extensive genetic variation with clear implications for their function, thus representing a substantial genetic risk factor for the pathogenesis of a range of chronic inflammatory disorders.

ASAS Centennial Paper: Impact of animal science research on United States goat production and predictions for the future.

Goat research in the United States has increased but at a rate less than that in production. Research on goat meat includes nutritional quality, packaging, color, sensory characteristics, and preslaughter management. Goat skins have value for leather, but quality of goat leather has not been extensively studied. Research in the production, quality, antibiotic residues, and sensory characteristics of goat milk and its products has aided development of the US dairy goat industry. Limited progress has been made in genetic improvement of milk or meat production. There is need to explore applications of genomics and proteomics and improve consistency in texture and functionality of goat cheeses. New goat meat and milk products are needed to increase demand and meet the diverse tastes of the American public. Despite research progress in control of mohair and cashmere growth, erratic prices and sale of raw materials have contributed to further declines in US production. Innovative and cooperative ventures are needed for profit sharing up to the consumer level. Internal parasites pose the greatest challenge to goat production in humid areas largely because of anthelmintic resistance. Study of alternative controls is required, including immunity enhancement via nutrition, vaccination, pasture management such as co-grazing with cattle, and genetic resistance. Similarly, the importance of health management is increasing related in part to a lack of effective vaccines for many diseases. Nutrition research should address requirements for vitamins and minerals, efficiencies of protein utilization, adjusting energy requirements for nutritional plane, acclimatization, and grazing conditions, feed intake prediction, and management practices for rapid-growth production systems. Moreover, efficient technology transfer methods are needed to disseminate current knowledge and that gained in future research.

The effect of diets on milk production and composition, and on lactation curves in pastured dairy goats.

A 2-yr study investigated effects of different levels of concentrate supplementation on milk production, composition, and lactation curves in pastured dairy goats. For both years, 44 Alpine goats (Capra hircus; 55 +/- 11 kg body weight) were randomly allocated to 4 groups. Animals were supplemented with 0.66 (treatments A and B), 0.33 (treatment C), or 0 kg of concentrate (treatment D) per kg of milk over 1.5 kg/d. Mixed vegetative forages were rotationally grazed by the goats (treatments B, C, and D), except that treatment A was confined and fed alfalfa hay. Individual milk production was recorded daily, and milk samples were collected once every 2 wk for the 7-mo period (March to September) and analyzed for fat, protein, lactose, urea-N, nonesterified fatty acids, and allantoin (second year only). Milk yield and composition varied among dietary treatments, with some measures affected by year. Average daily milk yield was lowest for treatment D. The increased level of concentrate supplementation in treatment A led to 22% greater milk yield compared with treatment D. Milk production increased by 1.7 and 0.9 kg for each additional kilogram of concentrate fed per day during the first and second years, respectively. Average peak yield, time of peak yield, and persistency were lower for treatment D than for other treatments. The percentage of milk fat was lower for treatment D than for other treatments. Concentration of milk protein was greater for treatments A and B during the first year, and was higher for treatment C than for other treatments during the second year. Average milk lactose concentration was higher for treatments B and C than for other treatments. However, milk urea-N concentration in treatment A was higher than other treatments. Milk allantoin, used to estimate microbial proteins synthesis, was 20 to 25% greater for treatment A than for other treatments. Averaged across year, plasma urea-N and nonesterified fatty acids concentration were lowest for treatment B. Average organic matter intake was similar among treatments during both years. Ratios of acetate and propionate concentrations for treatment A were lowest among treatments. In conclusion, milk production and composition were affected by the feeding treatment and year. Increased level of nutrition lead to an increase in daily milk yield, peak yield, time of peak yield, and persistency compared with treatment D. Alpine dairy goats grazing on fresh forages without concentrate supplementation can produce milk inexpensively, and response to concentrate supplementation is greater for low quality pasture.

The effect of grazing forage containing condensed tannins on gastro-intestinal parasite infection and milk composition in Angora does.

The objective of this study was to evaluate effects of the condensed tannin (CT)-containing forage sericea lespedeza (sericea lespedeza (SL); Lespedeza cuneata; 15.2% CT), on fecal egg count (FEC), larval development (larvae/10 g of feces), worm burden and immune response compared with a crabgrass (Digitaria ischaemum)/Kentucky 31 tall fescue (Festuca arundinacea; control forage (CTF)) forage low in CT (0.32% CT) in grazing Angora does and their kids. Fifty worm-free mixed-age does were randomly allocated to three treatments. One treatment (10 does; initial liveweight (LW) = 45+/-1.5 kg) entailed grazing of SL forage from April 25 to July 15, 2002 with a second treatment of CTF (20 does; initial LW = 43+/-1.4 kg) grazing during the same period. Does of the third treatment (20 does; initial LW = 44+/-1.4 kg) grazed a sward of SL for 2 weeks and then one of CTF for 2 weeks followed by alternating between the two pastures every 2-week rotational grazing (ROT). To gauge levels of infective larvae on pasture, three worm-free Angora kids (initial LW = 3.6+/-0.2 kg) were randomly selected as tracers. Tracers grazed for final 60 days and were euthanized for determination of worm burden. The immune response of does was measured by skin thickness reaction after the intradermal injection of 250 microg phytohemagglutinin (PHA). Mean FEC for SL and ROT were substantially lower (P < 0.01) than for CTF does (145, 329 and 894 eggs/g, respectively). The FEC for kids was lower (P < 0.05) for SL than for ROT and CTF (550, 2757 and 3600 eggs/g, respectively). Total fecal egg output (3.3, 6.0 and 26.9 x 10(5) eggs/day, respectively) and larval development (242, 263 and 792 larvae/10 g, respectively) were lower (P < 0.05) for SL and ROT than for CTF. Tracers grazing on SL had lower total worm burdens than ROT and CTF (P < 0.01). The immune response was higher (P < 0.01) for SL (4.9 mm) and ROT (6.0 mm) than for CTF (3.0 mm) at 12 h after injection of PHA. The packed cell volume (PCV) in does was higher (P < 0.01) for SL and ROT than for CTF (27, 26 and 23%, respectively). Does that grazed CT-containing forage had considerably lower milk somatic cell counts (SCC) than does grazing non-CT-containing forage. In summary, grazing CT forages reduced FEC, larval development and worm burden, and also appeared to enhance immune response. The CT-containing forage SL reduced gastro-intestinal parasite infections of Angora does and kids.

Divalent cation-dependent and -independent augmentation of macrophage phagocytosis of apoptotic neutrophils by CD44 antibody.

Phagocytosis of apoptotic neutrophils by macrophages is required for resolution of an inflammatory response. Removal of intact apoptotic neutrophils prevents the release of cytotoxic granules that would otherwise cause tissue damage and may lead to development of fibrosis. Importantly, macrophage phagocytosis of apoptotic neutrophils fails to induce release of proinflammatory mediators, consistent with a 'safe' pathway for disposal of potentially harmful inflammatory cells. One pathway for increasing phagocytosis of apoptotic cells to allow matching of tissue phagocyte capacity to apoptotic cell load in vitro is via antibody-mediated cross-linking of CD44, providing a mechanism for limiting tissue damage during resolution of inflammation. In this study, we have defined divalent cation-dependent and -independent actions of the CD44 antibody. For the divalent cation-independent CD44 antibody effect, we provide evidence that 'enabled' CD32 on the apoptotic neutrophil binds to intact CD44 antibody on the macrophage surface. One implication is that macrophages can phagocytose apoptotic neutrophils that are 'tethered' to the macrophage surface in a manner that is independent of defined apoptotic mechanisms. These data also provide an explanation for the greater efficacy of intact CD44 antibody when compared with F(ab')2 fragments.

Phagocytosis of opsonized apoptotic cells: roles for 'old-fashioned' receptors for antibody and complement.

Efficient phagocytic clearance of apoptotic cells is crucial in many biological processes. A bewildering array of phagocyte receptors have been implicated in apoptotic cell clearance, but there is little convincing evidence that they act directly as apoptotic cell receptors. Alternatively, apoptotic cells may become opsonized, whereby naturally occurring soluble factors (opsonins) bind to the cell surface and initiate phagocytosis. Evidence is accumulating that antibodies and complement proteins opsonize apoptotic cells, leading to phagocytosis mediated by well-defined 'old-fashioned' receptors for immunoglobulin-Fc and complement. In this review we summarize the evidence that opsonization is necessary for high capacity clearance of apoptotic cells, which would render putative direct apoptotic cell receptors redundant.

Progressive pneumonia complicating steroid-dependent asthma.

We describe a patient who developed pulmonary nocardiosis whilst taking long term oral steroids for asthma. Nocardiosis is more common than is generally appreciated by clinicians, is notoriously difficult to diagnose, and is associated with significant mortality. This patient developed progressive pneumonia despite antibiotic therapy, which is typical of pulmonary nocardiosis. It is important to consider this treatable condition in the differential diagnosis of pneumonia.

Growth and slaughter traits of Boer x Spanish, Boer x Angora, and Spanish goats consuming a concentrate-based diet.

The number of Boer crossbred meat goats has been increasing rapidly, although how their growth and slaughter traits compare with those of Spanish goats and influences of maternal genotype have not been thoroughly evaluated. This information would be useful to achieve optimal meat goat production systems and yield of goat products desired by consumers. Therefore, postweaning growth (9 to 24 wk of age) and slaughter traits (212 +/- 5.0 d of age) of Boer x Spanish, Spanish, and Boer x Angora wethers (n = 16, 18, and 18 for growth measures, respectively, and n = 6 per genotype for slaughter traits) consuming a concentrate-based diet were compared. Over the 16-wk performance period, ADG, DMI, and ADG:DMI were greater (P < 0.05) for Boer crossbreds than for Spanish goats (ADG: 154, 117, and 161 g; DMI: 646, 522, and 683 g/d; ADG:DMI: 263, 235, and 261 g/kg for Boer x Spanish, Spanish, and Boer x Angora, respectively). Dressing percentage (46.3, 47.3, and 47.0% of BW; SE = 1.21) and quality grade score (11.17, 9.67, and 11.17 for Boer x Spanish, Spanish, and Boer x Angora, respectively; SE = 0.66 [12 = Choice+; 11 = Choice; 10 = Choice-; 9 = Good+]) were similar among genotypes. Weights of some noncarcass components were greater for Boer crossbreds than for Spanish goats, but relative to empty BW, noncarcass component weights were similar among genotypes. Concentrations of moisture, ash, fat, and protein in carcass and noncarcass components did not differ among genotypes. Contributions to the carcass of different primal cuts were similar among genotypes, and there were few differences in concentrations of separated lean, bone, and fat in primal cuts. In conclusion, when consuming a concentrate-based diet, early postweaning growth rate was similar between Boer x Spanish and Boer x Angora wethers and greater for Boer crossbreds than for Spanish wethers. Slaughter traits were primarily related to differences in final BW.

Effects of dietary tallow level on performance of Alpine does in early lactation.

Sixty Alpine does (initial BW 47+/-1.3kg) were used to determine effects of dietary inclusion of different levels of partially hydrogenated tallow on performance in early lactation (weeks 3-11). Treatments entailed a 30% concentrate, negative control (NC) diet and five diets higher in concentrate (42-46%) with 0, 1.5, 3.0, 4.5 or 6.0% DM of partially hydrogenated tallow (0T, 1.5T, 3.0T, 4.5T and 6.0T, respectively). DM intake was 1.54kg per day for the NC and 1.86, 1.80, 1.99, 2.17 and 1.96kg per day for the five tallow treatments, respectively, BW was similar among treatments and increased as the trial progressed (47.4, 48.4, 49.8, 50.4, 50.8 and 51.3kg at weeks 3, 5, 7, 9, 11 and 13, respectively). Milk yield was lower (P<0.05) for NC (2.61kg per day) compared with the mean of the other diets and changed quadratically (P<0.05) as tallow level increased (2.85, 3.08, 3.14, 3.21 and 2.69kg per day for the five tallow treatments, respectively). Milk fat concentration was lower (P<0.05) for NC (2.94%) than for the mean of other diets and increased linearly (P<0.05) with increasing tallow level (3.00, 3.17, 3.34, 3.48 and 3.58%) whereas, milk protein concentration was not affected by level of tallow (2.72, 2.80, 2.93, 2.85, 2.90 and 2.90% for NC, and the five tallow treatments, respectively). The estimated NE(l):4% fat-corrected milk yield ratio was 0.93Mcal/kg for NC and 1.30, 1.11, 1.21, 1.37 and 1.44Mcal/kg for the five tallow treatments, respectively. The results indicated that in Alpine does, milk yield in early lactation increased as dietary tallow level was increased to 3 and 4.5% but decreased when the level was increased to 6%, although milk fat concentration increased linearly and the protein level was unchanged. These results suggest beneficial usage by lactating Alpine does of low to moderate levels of partially hydrogenated tallow in diets moderate in concentrate level, although ingredient availability and costs will influence ultimate dietary ingredient decisions.

Should aminophylline be abandoned in the treatment of acute asthma in adults?

Intravenous aminophylline is widely used for the treatment of acute asthma and anecdotes about its apparent effectiveness abound. Early studies demonstrated that aminophylline is an inefficient bronchodilator compared with adrenergic agonists given by injection or inhalation. This paper presents the results of a review of randomized controlled trials examining the effect of adding aminophylline to standard modern therapy with a nebulized beta(2) agonist and systemic corticosteroids in acute asthma in adults. Six of the seven trials, comprising 343 patients, failed to demonstrate any beneficial effect of aminophylline. Furthermore, minor toxicity was common. There is presently no evidence to support the use of aminophylline in addition to standard therapy for acute asthma in adults.

Molecular characterization of the surface of apoptotic neutrophils: implications for functional downregulation and recognition by phagocytes.

We have used a panel of monoclonal antibodies and lectins to examine the profile of surface molecule expression on human neutrophils that have undergone spontaneous apoptosis during in vitro culture. Neutrophil apoptosis was found to be accompanied by down-regulation of the immunoglobulin superfamily members PECAM-1 (CD31), ICAM-3 (CD50), CD66acde, and CD66b and the integrin-associated proteins CD63 and urokinase plasminogen activator receptor (CD87) that may alter the potential for adhesive interactions. Cellular interactions may be further influenced by the reduction of the expression of surface carbohydrate moieties, including sialic acid. Reduced expression of FcgammaRII (CD32), complement receptor type 1 (CD35) and receptors for pro-inflammatory mediators C5a (CD88) and TNFalpha (CD120b) associated with apoptosis might limit neutrophil responsiveness to stimuli that trigger degranulation responses. Although many of the receptors we have examined are expressed at reduced levels on apoptotic neutrophils, we found that there was differential loss of certain receptors (e.g. CD16, CD15 and CD120b) and increased expression of aminopeptidase-N (CD13). Together with our previous data showing that expression of certain molecules e.g. LFA-3 (CD58) is not altered during neutrophil apoptosis, these data are suggestive of specific changes in receptor mobilisation and shedding associated with apoptosis. Although reduced expression of CD63 (azurophilic granules) and CR1 (specific granules) indicates that granule mobilisation does not accompany apoptosis, a monoclonal antibody (BOB78), that recognises a 90 kDa antigen localised in intracellular granules, defines a subpopulation of apoptotic neutrophils that exhibit nuclear degradation yet retain intact plasma membranes. BOB78 positive neutrophils were found to bind biotinylated thrombospondin, suggesting that this mAb defines surface molecular changes associated with exposure of thrombospondin binding moieties.