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Biomedical subjects

R F Slocombe

Publications and source records attributed to R F Slocombe.

At least 55 records · Page 3Linked to original sources
PubMed1990

Development of morphologic, hemodynamic, and biochemical changes in lungs of rats given monocrotaline pyrrole.

A single, intravenous administration of a low dose of monocrotaline pyrrole (MCTP), a derivative of the pyrrolizidine alkaloid monocrotaline (MCT), induces progressive pulmonary hypertension and right ventricular hypertrophy (RVH) in rats. The temporal relationship between morphologic alterations, biochemical markers of lung injury, and the development of pulmonary hypertension was determined during the developing pulmonary disease. Three days after a single iv injection of 3.5 mg/kg MCTP, small increases in bronchoalveolar lavage (BAL) fluid lactate dehydrogenase (LDH) activity and accumulation in the lungs of intravenously administered 125I-bovine serum albumin (BSA) were associated with minimal to mild interstitial edema around large airways and blood vessels. By Day 5, BAL fluid LDH activity and 125I-BSA accumulation had increased further, and lung weight/body weight ratio and BAL fluid protein concentration were greater than those of control. Interstitial edema was more pronounced and involved patches of alveolar septal walls. A mild increase in numbers of mononuclear cells, including hypertrophied interstitial cells, was evident in these areas. Walls of pulmonary arteries less than 60 microns in diameter were mildly thickened. By Day 8, scattered clusters of alveolar sacs contained serous exudate, and interstitial mononuclear infiltrates were more pronounced. Mild to moderate thickening of arterial walls was apparent in small and large vessels. By Day 14, pulmonary arterial pressure was elevated and RVH was evident. Arterial walls were thickened and had hypertrophy of medial smooth muscle cells and intercellular edema, which was particularly prominent in areas with perivascular interstitial inflammation. Large patches of lung interstitium and alveolar lumens contained serous or fibrinous exudate. In summary, a single, intravenous administration of MCTP induced a delayed and progressive pulmonary microvascular leak, interstitial inflammation, and alterations in muscular blood vessels which resulted in pulmonary hypertension within 14 days. These morphologic, biochemical, and hemodynamic changes are nearly identical to alterations induced by the parent alkaloid, MCT.

Animals↗
PubMed1990

Morphologic and ultrastructural evaluation of effect of ischemia and dimethyl sulfoxide on equine jejunum.

Morphologic changes in equine jejunal segments subjected to 1 hour of ischemia and 1 hour of reperfusion, and protective effects of systemic administration of dimethyl sulfoxide (DMSO; 1 g/kg of body weight) were investigated in 18 ponies, using light microscopy and scanning and transmission electron microscopy. Ponies were allotted to 4 groups: group 1--control (n = 3); group 2--DMSO (n = 3); group 3--ischemia (n = 6); and group 4--ischemia and DMSO (n = 6). In each pony, 2 jejunal sections were evaluated. The first section was obtained prior to induction of ischemia, and the second was obtained 2 hours later after reperfusion. Mucosal lesions were graded from 0 (normal) to 5 (most severe). Combined ischemia and reperfusion of 2 hours' duration induced moderately severe mucosal injury to the equine jejunum (group 3; grade 1.5 to 2.5), characterized principally by disruption of enterocyte attachment from the basement membrane and lamina propria. Fluid accumulation disrupted enterocyte cell-to-cell adhesion toward cell bases, while apical tight junctions and desmosomal junctions toward the luminal surface remained intact. Intracytoplasmic organellar changes within enterocytes were not a prominent feature of the injury. The aforementioned processes were marked at the villus tip and progressed down the villus sides. These findings support the importance of mechanisms leading to early subepithelial fluid accumulation rather than that of direct severe enterocyte injury. Further, fluid accumulation does not appear to arise from intercellular migration from the luminal surface. In this model, a pathomechanical effect caused by vigorous villus retraction appears to exacerbate epithelial lifting toward the villus tip.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of Pasteurella haemolytica-derived endotoxin on pulmonary structure and function in calves.

The role of endotoxin in the pathogenesis of acute pneumonic pasteurellosis is uncertain. Recently, we reported that Escherichia coli-derived endotoxin given by airway inoculation fails to induce lung injury in calves. Because Pasteurella haemolytica-derived endotoxin may differ substantially from E coli in its pathogenicity, we repeated these studies with Pasteurella endotoxin. Intratracheal inoculation of P haemolytica endotoxin caused hypoxemia and increased the alveolar-arterial oxygen differences without causing hypercarbia or changes in lung mechanical properties and volumes. In contrast, IV inoculation of endotoxin caused systemic hypotension, leukopenia, gas exchange impairment, increased total pulmonary resistance, and decreased dynamic compliance. Both routes of inoculation increased serum endotoxin concentrations and were associated with areas of pulmonary hemorrhage, edema, and acute inflammation. We concluded that P haemolytica-derived endotoxin is pathogenic by IV and airway routes of inoculation, and therefore differs from E coli endotoxin in its ability to induce lung lesions in calves.

Animals↗
PubMed1990

Effect of deferoxamine pretreatment on acute pneumonic pasteurellosis and neutrophil oxidative metabolism in calves.

Iron plays a central role in bacterial infections, influencing both bacterial virulence and host cellular defense mechanisms. We investigated whether iron chelation might be of benefit in the treatment of pneumonic pasteurellosis of calves. Neutrophils obtained from calves previously treated with the iron chelator, deferoxamine, were studied for their responses to latex and opsonized zymosan by luminol-enhanced chemiluminescence and to phorbol myristate acetate and opsonized zymosan by superoxide generation. Treatment with deferoxamine in vivo failed to influence these in vitro measures of neutrophil oxidative metabolism. Furthermore, iron depletion with deferoxamine failed to modify the pathophysiological derangements that occurred in calves following experimental induction of pneumonia by intratracheal inoculation with Pasteurella haemolytica. These data indicate that iron chelation using deferoxamine cannot be recommended as an adjunct to conventional therapy in the treatment of pneumonic pasteurellosis of cattle.

Acute Disease↗
PubMed1989

Clinical, radiographic, pathologic, and genetic features of osteochondrodysplasia in Scottish deerhounds.

Clinical, radiographic, pathologic, and genetic features of a form of osteochondrodysplasia in 5 related Scottish Deerhound pups from 2 litters were evaluated. All pups appeared to be phenotypically normal at birth. At approximately 4 or 5 weeks, exercise intolerance and retarded growth were observed. Kyphosis, limb deformities, and joint laxity gradually developed. Radiography of the affected pups revealed skeletal changes characterized by abnormalities in long bones and vertebrae, with involvement of epiphyses, growth plates, and metaphyses. Short long bones and vertebrae and irregular and delayed epiphyseal ossification were most noticeable in younger pups; in older pups, bony deformities became more prominent. In skeletally mature dogs, osteopenia and severe deformities were seen. The histologic changes of the growth plate were compatible with a diagnosis of chondrodysplasia. Growth plate chondrocytes contained periodic acid Schiff-positive, diastase-resistant cytoplasmic inclusions. A single autosomal recessive mode of inheritance was suspected.

Animals↗
PubMed1989

Leucoencephalomyelopathy in Australian Rottweiler dogs.

Clinical and pathological studies of a neurological disorder of 3 adult Rottweiler dogs are described. Dogs developed proprioceptive losses involving the limbs, leading to progressively worsening ataxia and hypermetria. Blood and CSF fluid analyses were normal and radiographs and myelograms showed no compressive lesions of the spinal cord. At necropsy, severe demyelination of the dorsal and lateral funiculi of the cervical spinal cord was visible grossly. Microscopically there was more extensive, symmetrical involvement of the spinal cord and brain than was apparent grossly, with demyelination of white matter tracts and sparing of axons in affected areas. These changes were considered diagnostic for leucoencephalomyelopathy. This condition has not been previously reported in Australia, and is probably transmitted genetically, presumably as an autosomal recessive trait.

Animals↗
PubMed1989

Histopathologic findings and energy dispersive X-ray spectroscopic analysis of experimentally induced foreign-body pneumonias in rats.

To document the diagnostic features of foreign-body pneumonias, four commonly used orally administered medicaments were instilled into the lungs of Sprague-Dawley rats. Rats in each group received a single 0.4 ml dose of either barium sulfate suspension (BaSO4), mineral oil, Pepto-bismol, or Kaopectate inoculated into a lung via a mainstem bronchus. The other lung served as a non-inoculated control. Rats were euthanatized on post-inoculation day 2 or 7 in order to document fully-developed acute pulmonary lesions and developing, chronic pulmonary lesions, respectively. Light microscopic features of BaSO4-inoculated lungs were distinctive from changes in mineral oil-inoculated lungs at both post-inoculation days. On post-inoculation day 2, rats inoculated with BaSO4 had pneumonia characterized by large numbers of alveolar macrophages containing green-to-brown granular material. There was minimal interstitial involvement. On post-inoculation day 2, mineral oil caused pneumonia characterized by giant cells and alveolar macrophages that had cytoplasms distended with variably-sized clear vacuoles. Lungs inoculated with BaSO4 or mineral oil had changed little on post-inoculation day 7 compared to the light microscopic features observed on day 2. On post-inoculation day 2, rats inoculated with either Pepto-bismol or Kaopectate had broncho-interstitial pneumonia with areas of necrosis and hemorrhage. On post-inoculation day 7, lungs inoculated with Pepto-bismol or Kaopectate had extensive fibrosis within alveolar lumens. Energy dispersive spectroscopy performed on sections of lung from rats given BaSO4, Pepto-bismol, and Kaopectate yielded a unique elemental spectrum for each compound in situ on post-inoculation days 2 and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Comparison of pathophysiologic changes in the lungs of calves challenge exposed with Escherichia coli-derived endotoxin and Pasteurella haemolytica, alone or in combination.

Pulmonary responses to intratracheal challenge exposure with Pasteurella haemolytica, with or without Escherichia coli-derived endotoxin, E coli endotoxin alone, or saline solution were compared in anesthetized, mechanically ventilated neonatal calves. Baseline values for dynamic compliance, total pulmonary resistance, functional residual capacity, arterial blood gas tensions, hemogram, leukogram, and systemic and pulmonary arterial pressures were recorded for each calf. After baseline data were obtained, calves were challenge exposed with logarithmic-growth phase P haemolytica organisms with or without E coli endotoxin, E coli endotoxin alone, or saline solution (0.9% NaCl). Physiologic data were obtained immediately after challenge exposure and at various intervals over the next 6 hours. Calves challenge exposed with P haemolytica alone developed sever hypoxemia, had increased alveolar-arterial oxygen difference and threefold increases in total pulmonary resistance, became hypercarbic, had decreased functional residual capacity, and developed systemic hypotension without change in pulmonary arterial pressure. At necropsy, these calves had extensive multifocal areas of necrohemorrhagic and purulent pneumonia. Ratio of extravascular lung water to lung dry weight was not significantly increased in lung specimens obtained from calves challenge exposed with P haemolytica, but ratio of lung wet weight to dry weight was increased, indicating that increased lung wet weight was attributable largely to increased solids and not to fluid alone. (Extravascular lung water measurement excludes fluid from the vascular compartment.) Intratracheal challenge exposure with endotoxin failed to alter lung function and caused minor changes in lung structure consisting of focal areas of hemorrhage and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of ischemia and dimethyl sulfoxide on equine jejunal vascular resistance, oxygen consumption, intraluminal pressure, and potassium loss.

Physiologic effects of 1 hour of ischemia and 1 hour of reperfusion on equine jejunum and protective effects of systemic administration of dimethyl sulfoxide (DMSO, 1 g/kg of body weight) were investigated in 18 ponies, using neurally intact segments of jejunum perfused at constant flow with heparinized blood. Ponies were allotted to 4 groups: group 1, saline solution administered (control, n = 3); group 2, DMSO administered (DMSO, n = 3); group 3, ischemia induced and saline solution administered (ischemia, n = 6); and group 4, ischemia induced and DMSO administered (ischemia-DMSO, n = 6). Intestinal vascular resistance (R, mm of Hg/ml/min/100 g), oxygen consumption (VO2, ml/min/100 g), frequency and amplitude of rhythmic changes in intraluminal pressure, intestinal compliance (C, ml/mm of Hg), and arteriovenous potassium concentration difference (delta AV [K+], mEq/L) were determined and compared with stable preischemic values within groups. There were no significant changes in any variable in ponies of groups 1 or 2. In ponies of group 3, significant (P less than or equal to 0.05) changes included: an initial increase in R during reperfusion, followed by a decrease to values below preischemic values by 15 minutes of reperfusion; decreased VO2 during the entire reperfusion period; increased amplitude of rhythmic contractions during initial reperfusion; decreased frequency of rhythmic contractions during ischemia; and increased delta AV [K+] during initial reperfusion. Changes in ponies of group 4 were identical to changes in ponies of group 3, with the exception that DMSO administration prevented the decrease in R during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Thoracic radiographic appearance during lung inflation in neonatal calves.

The effect of lung inflation on thoracic radiographic anatomy was determined in seven anesthetized calves less than one week of age. Radiographs were taken with the calves in dorsoventral (DV), ventrodorsal (VD), left and right lateral recumbency at functional residual capacity (FRC), at half inflation of the lung and at total lung capacity (TLC). Lung volumes were maintained by positive pressure ventilation. Increases in areas and linear dimensions during lung inflation were not uniform, being greatest in the caudal and especially the caudal ventral regions of the thorax. With inflation, heart size decreased and the heart shadow moved caudad as the diaphragm flattened. When the calf was shifted from the DV to the VD position, the heart displaced toward the left thoracic wall. Lung areas were larger on VD than on DV projections with the right lung being larger than the left. On lateral radiographs the most reliable, easily observed indication of the stage of lung inflation was the area bounded by the vena cava, the caudal heart border and the diaphragm. On the DV or VD radiographs the transthoracic width at the diaphragm was the best indicator of the degree of lung inflation.

Animals↗
PubMed1988

Invasive pulmonary aspergillosis of horses: an association with acute enteritis.

Invasive pulmonary aspergillosis was identified in 19 horses. In 16 cases mycotic lesions were associated with enterocolitis; 14 cases appeared to result from Salmonella infection. Pulmonary lesions included multifocal areas of acute necrosis, leukocytoclastic vasculitis, and thrombosis with fibrinosuppurative inflammation surrounding mycelial masses. Thromboemboli with fungi were in the brain and kidneys of three cases. Factors which appeared to predispose to pulmonary aspergillosis included corticosteroid therapy, disseminated neoplasms, hepatitis, pleuritis, and peritonitis. This study suggests that immunocompromise and invasion of Aspergillus sp. from damaged intestine are more important in causing equine pulmonary aspergillosis than inhalation of spores.

Acute Disease↗
PubMed1988

Percutaneous biopsy of the proximal humeral growth plate in dogs.

A percutaneous biopsy technique for the study of endochondral bone formation in the dog was developed. With the dogs under general anesthesia or sedated with a combination of a tranquilizer and a local anesthetic, biopsy specimens were obtained from the proximal growth plate of the humerus with the use of a Jamshidi bone biopsy needle. Biopsy specimens were structurally intact, and contained epiphysis, growth plate, and metaphysis. The procedure proved to be a simple, safe technique, which caused minimal discomfort for the patient and did not affect the growth of the proximal end of the humerus, even after multiple biopsies.

Animals↗
PubMed1987

Immotile cilia syndrome in an aged dog.

An 11-year-old Dalmatian was examined and treated for bilateral nasal discharge and cough of 6 months' duration. Response to medical treatment and surgical intervention was unsatisfactory. Histologic examination of lung tissue revealed chronic severe catarrhal bronchitis and bronchiolitis with bronchiectasis. Histologic findings and barium sulfate bronchography indicated abnormal mucociliary clearance in the respiratory tract. Electron microscopy revealed abnormalities or deletions of outer and/or inner dynein arms in 26% of the ciliary profiles from the affected dog. Similar abnormalities were not found in 500 ciliary profiles from age- and gender-matched control dogs.

Animals↗
PubMed1987

Micropolyspora faeni causes airway inflammation but not hyperresponsiveness in sensitized ponies.

We assessed the effect of aerosol Micropolyspora faeni challenge in two groups of ponies by measuring lung function, airway reactivity to aerosol histamine, and bronchoalveolar lavage fluid cytology. One group of ponies was sensitized by subcutaneous injection of M. faeni in complete Freund's adjuvant, and the other group served as control. In both groups of ponies, measurements were made at base line and 5 h after aerosol administration of 30 ml of saline or 30 ml of 1% wt/vol particulate M. faeni antigen in saline. Saline challenge had no effect on any of the measured variables. M. faeni challenge had no effect on pulmonary mechanics or gas exchange in the control group but significantly increased respiratory frequency and minute ventilation and decreased arterial CO2 tension in the sensitized ponies. In both groups of ponies, aerosol M. faeni challenge significantly increased total white blood cell count and neutrophil numbers in bronchoalveolar lavage fluid while large mononuclear cell numbers decreased. Airway responsiveness was unaltered by saline or M. faeni challenge in both pony groups. We conclude that aerosol M. faeni challenge induces pulmonary neutrophilia and abnormalities of ventilation but is not accompanied by airway hyperresponsiveness in sensitized ponies.

Aerosols↗