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Biomedical subjects

R F Slocombe

Publications and source records attributed to R F Slocombe.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sequential changes in bronchoalveolar cytology after autologous blood inoculation.

Six horses, free of recent exercise-induced pulmonary haemorrhage (EIPH), each had 8 bronchial segments inoculated with 40 ml of autologous blood lavaged on Days 3, 5, 7, 10, 14 and 21 after inoculation. The bronchoalveolar lavage (BAL) fluid samples were analysed, and total leucocyte counts and differential cell percentages determined. Statistical analysis of the differences between the 8 post inoculation and 1 pre-inoculation (control) lavage sites demonstrated an early neutrophilic response, rising from < 5% of alveolar leucocytes to 10% by 24-48 h post inoculation. As this response waned, macrophage numbers increased and persisted at mildly elevated levels for the remainder of the experiment. Small numbers of erythrophagocytes were observed prior to 3 days post inoculation, but their numbers increased 10-fold by Day 10. In the first 3 days, blood was observed endoscopically streaming from inoculated lung regions, suggesting that mucociliary clearance is a major mechanism of early erythrocyte clearance. However, both free and phagocytosed whole erythrocytes were recovered in lavages 14 days after inoculation with small numbers of erythrocytes still present at 21 days. We conclude that intrapulmonary blood provokes a mild, but prolonged inflammatory reaction and that the removal of alveolar haemorrhage is dependent on a combination of mucociliary clearance and phagocytic mechanisms. Erythrophagocytosis is slow to commence and the removal of blood prolonged, suggesting that horses in fast work, sufficient to induce EIPH, are unlikely to recover fully if intervals between strenuous work are less than 14 days.

Animals↗
PubMed1999

Effect of intravenous administration of furosemide on mass-specific maximal oxygen consumption and breathing mechanics in exercising horses.

OBJECTIVES: To determine whether i.v. administration of furosemide (250 mg) to horses before maximal exercise affected maximal oxygen consumption (VO2max), breathing mechanics, or gas exchange during exercise. ANIMALS: 7 healthy, well-conditioned Thoroughbred horses. PROCEDURES: 5 horses initially performed an incremental treadmill exercise test to determine VO2max 4 hours after i.v. administration of furosemide (250 mg i.v.) or placebo (saline [0.9% NaCl] solution). Time to fatigue and distance run were recorded. All 7 horses were then used to determine the effects of furosemide on gas exchange and breathing mechanics at 40, 60, 80, and 100% of VO2max. Horses were weighed immediately before exercise. RESULTS: Furosemide treatment significantly increased mass-specific VO2max (5.3%), but absolute VO2max was not significantly altered. In the 2 parts of the study, body weights were 2.9 and 2.5% higher when horses were given placebo than when they were given furosemide. Time and distance run at speeds > or = 11.0 m/s were significantly greater following furosemide administration. Furosemide treatment had no effect on breathing mechanics or gas exchange. CONCLUSIONS AND CLINICAL RELEVANCE: Previous studies have suggested that prerace administration of furosemide may have a positive effect on performance. Results of this study indicate that this may be attributable, in part, to an increase in mass-specific VO2max but not to improvements in breathing mechanics or gas exchange. Most of the increase in mass-specific VO2max appeared to be attributable to weight loss associated with diuresis induced by furosemide.

Animals↗
PubMed1999

Fibrous osteodystrophy in dromedary camels (Camelus dromedarius).

Fibrous osteodystrophy of the facial and long bones was diagnosed in four dromedary camels (Camelus dromedarius). None of the animals responded to treatment with antiinflammatory medications or calcium supplements. The lesions were probably caused by multiple factors, including inappropriate diet and gastrointestinal parasitism. A critical factor in lesion formation may have been vitamin D deficiency secondary to gastrointestinal malabsorption and inadequate winter exposure to ultraviolet light.

Animals↗
PubMed1998

Effect of prolonged heavy exercise on pulmonary gas exchange in horses.

During short-term maximal exercise, horses have impaired pulmonary gas exchange, manifested by diffusion limitation and arterial hypoxemia, without marked ventilation-perfusion (VA/Q) inequality. Whether gas exchange deteriorates progressively during prolonged submaximal exercise has not been investigated. Six thoroughbred horses performed treadmill exercise at approximately 60% of maximal oxygen uptake until exhaustion (28-39 min). Multiple inert gas, blood-gas, hemodynamic, metabolic rate, and ventilatory data were obtained at rest and 5-min intervals during exercise. Oxygen uptake, cardiac output, and alveolar-arterial PO2 gradient were unchanged after the first 5 min of exercise. Alveolar ventilation increased progressively during exercise, from increased tidal volume and respiratory frequency, resulting in an increase in arterial PO2 and decrease in arterial PCO2. At rest there was minimal VA/Q inequality, log SD of the perfusion distribution (log SDQ) = 0.20. This doubled by 5 min of exercise (log SDQ = 0.40) but did not increase further. There was no evidence of alveolar-end-capillary diffusion limitation during exercise. However, there was evidence for gas-phase diffusion limitation at all time points, and enflurane was preferentially overretained. Horses maintain excellent pulmonary gas exchange during exhaustive, submaximal exercise. Although VA/Q inequality is greater than at rest, it is less than observed in most mammals and the effect on gas exchange is minimal.

Animals↗
PubMed1996

Characterisation of haemolytic RTX toxins produced by Australian isolates of Actinobacillus pleuropneumoniae.

The haemolytic RTX toxins of 27 isolates of Actinobacillus pleuropneumoniae, representing all serovars that have been isolated in Australia, were characterised. The quantity of protein secreted by these isolates into the media was not significantly different between serovars, but haemolytic activity was detected only in the unconcentrated supernatants from cultures of serovar 1 and 5 isolates. Haemolytic activity in supernatants of serovar 2, 3 and 7 isolates was detected only after the supernatants were concentrated. On Southern hybridisation blots, genomic DNA of serovar 1 and 5 isolates contained regions that were similar to the cloned structural genes for ApxI (apxIA) and for ApxII (apxIIA). In contrast, genomic DNA of serovar 2, 3 and 7 isolates only contained regions similar to, if not identical with, the cloned apxIIA gene. The haemolytic activity of the culture supernatant depends on the type or composition of media and adaptability of the bacteria to in-vitro cultivation. Low passage cultures of A pleuropneumoniae, which were characterised by waxy colonies, produced significantly weaker haemolytic activity than A pleuropneumoniae after several passages in vitro.

Actinobacillus Infections↗
PubMed1995

Definition of chemiluminescence and superoxide production responses of bovine neutrophils to selected soluble and particulate stimulants, and comparisons with the responses to Pasteurella haemolytica.

We defined methods for use of luminol-dependent chemiluminescence (LDCL) and superoxide anion (O2-) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the LDCL and O2- responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly LDCL, were characterized by marked day-to-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability. We compared the in vitro oxidative (LDCL and O2-) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists--latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan--with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the LDCL and O2- responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists. We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Furthermore, the in vitro generation of reactive oxygen species, including O2- by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.

Adjuvants, Immunologic↗
PubMed1995

Enzyme release by bovine neutrophils.

Release of enzymes from cytoplasmic granules has been postulated to have a major role in neutrophil-mediated tissue injury. Secretion or release of primary granules, specific granules, and cytosolic enzymes by bovine neutrophils was examined by quantifying the release of beta-glucuronidase, B12-binding protein, and lactate dehydrogenase, respectively, in response to predetermined amounts of phorbol myristate acetate, calcium ionophore, and opsonized zymosan. These responses were compared with the enzyme release induced by exposure to live or dead, unopsonized or opsonized Pasteurella haemolytica. The greatest release of beta-glucuronidase, B12-binding protein, and lactate dehydrogenase was observed in neutrophils exposed to live organisms partially because of neutrophil lysis. Bovine neutrophils respond markedly to particulate agonists, live or dead, pathogenic or nonpathogenic, by a selective release of specific granules, an effect enhanced by opsonization. Particulate agonists induce minimal primary granule release other than that induced by cell death. Because bovine neutrophils contain quantitatively high numbers of specific granules, the high rate of secretion/release in response to P haemolytica organisms could have a major role in the tissue responses that characterize the lesions of pneumonic pasteurellosis.

Analysis of Variance↗
PubMed1994

Functional and structural changes of porcine alveolar macrophages induced by sublytic doses of a heat-labile, hemolytic, cytotoxic substance produced by Actinobacillus pleuropneumoniae.

Alterations in the size and functions of porcine alveolar macrophages exposed to sublytic amounts of heat-labile, hemolytic cytotoxin produced by Actinobacillus pleuropneumoniae (App) serotype 1, strain HS54 into the culture medium were studied in vitro. Alveolar macrophages were sensitive to the cytotoxin; treatment of the macrophages with low concentrations of cytotoxin (0.016 hemolytic unit) resulted in severe, irreversible cell swelling. However, high doses of cytotoxin (2.0 hemolytic units) were required to cause substantial cell death, as indicated by the influx of propidium iodide into and release of lactate dehydrogenase from cells. Macrophages exposed to low, sublytic doses of cytotoxin failed to migrate toward chemoattractant, were unable to attach to glass, and failed to phagocytize optimally opsonized erythrocytes. Macrophages already attached to glass surfaces detached when exposed to sublytic doses of cytotoxin. The swelling and impairment of functions of alveolar macrophages observed in this study could not be attributed to endotoxic effects, because heat treatment of the cytotoxin preparation for 60 minutes at 60 C resulted in complete loss of cytotoxicity. We conclude that sublytic doses of heat-labile, hemolytic cytotoxic substances produced by App depress alveolar macrophage function at concentrations likely to develop in association with acute pulmonary infection with App. The Apx (A pleuropneumoniae Rtx toxins) exotoxins secreted by the bacteria into culture medium were considered responsible for the toxic activity of the cytotoxin preparation. The Apx of the App field strain used in this study were likely to be similar to those of serotype-1 reference strain (S4707). Analysis by use of DNA-DNA hybridization indicated that genomic DNA of the field strain contained sequences similar to those encoding structural protein of ApxI (apxIA) and ApxII (apxIIA) of the serotype-1 reference strain. Therefore, Apx produced by the field strain of App used in this study are likely to be of similar pathogenic importance worldwide.

Actinobacillus pleuropneumoniae↗
PubMed1994

Influence of air movement, facemask design and exercise on upper airway, transpulmonary, and transdiaphragmatic pressures in thoroughbred horses.

The influences of facial airflow, exercise and wearing a facemask on gas exchange and upper airway (Pu), transpulmonary (PTP) and transdiaphragmatic (PTD) pressures were investigated in 6 horses performing an incremental exercise test on an inclined (10%) treadmill. The test consisted of a 2 min walk followed by two 2 min exercise bouts at intensities which produced 40% and 80% of maximal oxygen consumption. Horses performed the test 4 times, once for each of 4 protocols, which involved not wearing a facemask (A), wearing a mask with either no biased flow through it (B), with an expiratory bias of 6300 L/min through it (C), or with an inspiratory bias of the same magnitude (D). Although no statistically significant differences in arterial blood gases, Pu, PTP, or PTD could be attributed to the various protocols, trends that may have been physiologically important were detected. Hypoxemia and hypercapnia associated with exercise were most marked with protocol B and least severe with protocols A or D. PTP was lowest for all tests with protocol D. Of the 3 conditions that required the wearing of a mask, protocol D was associated with the lowest Pu. While impelling air into the respiratory tract, as presumedly occurs with horses exercising over ground, may enhance respiratory function during exercise, this preliminary study does not clearly demonstrate this. Because this is an important consideration when conducting studies involving horses on treadmills, further investigations at higher exercise intensities and with additional methodologies are needed to clarify the issue.

Acid-Base Equilibrium↗
PubMed1992

Respiratory mechanics of horses during stepwise treadmill exercise tests, and the effect of clenbuterol pretreatment on them.

Normal Standardbred horses were given an incremental exercise test on a horizontal treadmill to evaluate the influence of exercise on gas exchange, resistance, dynamic compliance and inertance of the respiratory system. The exercise test consisted of 2 min exercise steps at each of the following speeds: 2.4 m/sec (walk), 4.5 m/sec (slow trot), 7.0 m/sec (fast trot) and 10 m/sec (gallop). At rest and after 1 min of exercise at each step, airflow, tidal volume, respiratory frequency, pharyngeal, mid-oesophageal and transdiaphragmatic pressures and arterial blood gas tensions were measured. The same horses were subsequently treated intravenously with clenbuterol (0.8 microgram/kg) and an identical exercise test and measurement performed 10 min after clenbuterol injection. In response to exercise, there were large increases in tidal volume, respiratory frequency, airflow and pressures. Exercise was associated with a decrease in upper airway resistance but total pulmonary resistance was unchanged. Exercise did not alter inertance or dynamic compliance, horses became hypoxaemic, and at 10 m/sec (galloping) also developed hypercarbia. Treatment with clenbuterol did not alter any of these measurements in response to exercise. These data suggest that dilation of upper airways occurs during exercise, and that inertial forces are important in strenuously exercising horses and may influence the accuracy of dynamic compliance determinations at high exercise intensities.

Airway Resistance↗
PubMed1992

Pathological aspects of Australian Stringhalt.

Nine horses with clinical signs of Australian Stringhalt were killed and tissues collected for a detailed pathological study. Lesions were limited to peripheral nerves and muscles. The most severely affected nerves were the superficial and deep peroneal, distal tibial, plantar digital, volar and recurrent laryngeal nerve with changes characterised by a selective loss of large diameter myelinated fibres with various degrees of demyelination, fibrosis, Schwann cell proliferation and onion-bulb formation. A routine evaluation of the brain and spinal cord by light microscopy failed to reveal any consistent abnormalities. Morphometric analysis of deep peroneal and recurrent laryngeal nerves confirmed the reduced number of large diameter myelinated axons. Teased fibre preparations of these nerves did not show any abnormalities in internodal distance. The most severe muscle lesions were in the long and lateral digital extensors, cranial tibial, dorsal cricoarytenoid, gracilis and lateral deep digital flexor with extensive atrophy of fibres and diffuse fibrosis. Histochemical evaluation of the long digital extensor from 3 affected horses showed an abnormally wide distribution in fibre size and a reduction in type II fibres compared with controls. These lesions are consistent with a distal axonopathy leading to neurogenic muscle atrophy. The distribution of neuromuscular lesions in Australian Stringhalt may be explained by the susceptibility of longer, larger myelinated nerve fibres to injury, but the cause for this distal axonopathy remains unknown.

Animals↗
PubMed1992

Epithelial strips: an alternative technique for examining arachidonate metabolism in equine tracheal epithelium.

We have developed an alternative method for examining equine tracheal epithelial arachidonic acid (AA) metabolism that utilizes strips of pseudostratified columnar epithelium attached to a layer of elastic tissue 80 to 130 microns thick. We compared the responses of this preparation with those of enzymatically dispersed suspensions of tracheal epithelium obtained from the same animal. Strips incubated with [3H]AA incorporated 40.8 +/- 3.6% of added radioactivity and released 2.55 +/- 0.23% of incorporated radioactivity when stimulated with 5 microM A23187. Values for the cell suspension were 59.6 +/- 1.6% and 1.90 +/- 0.08%, respectively. Stimulation with 50 microM histamine or bradykinin resulted in significant release of free [3H]AA only from the strips. High-performance liquid chromatography radioactivity profiles of eicosanoids released following stimulation with 5 microM A23187 demonstrated peaks that coeluted with free AA, prostaglandin (PG) E2, and PGF2 alpha for the strips, and free AA, leukotriene B4, and 5-HETE for the cell suspensions. The absence of PGE2 production by cell suspensions was confirmed by assaying immunoreactive PGE2 in supernatants from unlabeled strips and suspensions stimulated with 5 microM A23187. Epithelial strips produced 10.3 +/- 1.3 ng PGE2/ml supernatant, whereas 5 x 10(6) cells in suspension produced less than 100 pg/ml. Despite the lack of PG production by the cell suspensions, immunocytochemical staining with an anti-PGH synthase antibody demonstrated the presence of PGH synthase in epithelial cells of both preparations. These data indicate that, in contrast to epithelial cell suspensions, epithelial strips synthesize cyclooxygenase metabolites and respond to peptide agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Exercise-induced pulmonary hemorrhage in horses with experimentally induced allergic lung disease.

The lungs of sensitized horses were exposed to aerosolized ovalbumin. Some horses (n = 4) were given ovalbumin in 1 lung only, whereas in others (n = 7), ovalbumin or vehicle were inoculated in the cranial, ventral, and caudal regions of the caudal lung lobe. Horses were exercised 5 hours after ovalbumin exposure. Immediately before exercise, endoscopy failed to reveal any abnormality. After exercise, endoscopic examination of horses subjected to unilateral ovalbumin exposure revealed extensive blood in airways leading to the exposed lung in all horses. Blood was not observed in the airways leading to the control lung. Mean (+/- SEM) minimum volume of the exposed and control lungs was 9.5 +/- 1.5 and 5.5 +/- 1.6 L, respectively; this difference was statistically significant (P less than 0.05). Bronchoscopy of horses subjected to regional ovalbumin or vehicle exposure and exercise revealed a small amount of blood-tinged fluid in the bronchi serving the regions of the lung inoculated with ovalbumin. Minimum volumes of such regions were not significantly different from one another. However, their minimum volume was significantly (P less than 0.05) larger than that of vehicle-inoculated regions. Gross and histologic examination confirmed inflammation and hemorrhage in the ovalbumin-exposed, but not the control lungs or lung regions. Thus, exercise can cause blood from an injured region of lung to appear in the larger airways. Regional differences in lung structure and function do not influence the appearance of blood in the airways.

Aerosols↗
PubMed1991

Experimental reproduction of respiratory tract disease with bovine respiratory syncytial virus.

An experiment was conducted to reproduce respiratory tract disease with bovine respiratory syncytial virus (BRSV) in one-month-old, colostrum-fed calves. The hypothesized role of viral hypersensitivity and persistent infection in the pathogenesis of BRSV pneumonia was also investigated. For BRSV inoculation a field isolate of BRSV, at the fifth passage level in cell culture, was administered by a combined respiratory tract route (intranasal and intratracheal) for four consecutive days. Four groups of calves were utilized as follows: Group I, 6 calves sham inoculated with uninfected tissue culture fluid and necropsied 21 days after the last inoculation; Group II, 6 calves inoculated with BRSV and necropsied at the time of maximal clinical response (4-6 days after the last inoculation); Group III, 6 calves inoculated with BRSV and necropsied at 21 days after the last inoculation; Group IV, 6 calves inoculated with BRSV, rechallenged with BRSV 10 days after initial exposure, and necropsied at 21 days after the initial inoculation. Clinical response was evaluated by daily monitoring of body temperature, heart rate, respiratory rate, arterial blood gas tensions, hematocrit, total protein, white blood cell count, and fibrinogen. Calves were necropsied and pulmonary surface lesions were quantitated by computer digitization. Viral pneumonia was reporduced in each principal group. Lesions were most extensive in Group II. Disease was not apparent in Group I (controls). Significant differences (p less than 0.05) in body temperature, heart rate, respiratory rate, arterial oxygen tension, and pneumonic surface area were demonstrated between control and infected calves. Results indicate that severe disease and lesions can be induced by BRSV in one-month-old calves that were colostrum-fed and seropositive to BRSV. BRSV rechallenge had minimal effect on disease progression. Based on clinical and pathological response, results did not support viral hypersensitivity or persistent infection as pathogenetic mechanisms of BRSV pneumonia.

Animals↗
PubMed1991

Use of phenytoin to treat horses with Australian stringhalt.

Five horses with Australian stringhalt were treated with 15 mg/kg phenytoin orally for 2 weeks. During the second week of the trial, 3 of the horses were given an additional dose of 10 mg/kg phenytoin. The response to treatment was clinically assessed by grading the severity of the gait abnormality at the walk, trot, turning and backing twice daily. There was a significant (P less than 0.05) improvement in the gait abnormality when pre-treatment values were compared with the mean of the last 3 assessments before treatment stopped. When reassessed 2 weeks after treatment ceased, there remained a significant (P less than 0.05) improvement compared with pre-treatment values at the trot and on backing, but not at the walk or turning. Surface electromyographic recordings were made weekly from the long digital extensor muscle, and there was a change to a near normal recording by the end of treatment. Plasma phenytoin concentrations were monitored during the trial, and the dose rates used achieved a steady state with a mean plasma level of 37 +/- 7 mumol/l. There was wide variability between plasma concentrations in different horses, although there was no difference in absorption between administration of the phenytoin as a paste, or when it was mixed in the feed. Although mild tranquilization was seen after treatment, there were no clinical, haematological or biochemical signs of toxicity from the phenytoin therapy.

Administration, Oral↗