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Biomedical subjects

M D McCracken

Publications and source records attributed to M D McCracken.

At least 19 recordsLinked to original sources

Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer.

In 1997, Wilmut et al. announced the birth of Dolly, the first ever clone of an adult animal. To date, adult sheep, goats, cattle, mice, pigs, cats and rabbits have been cloned using somatic cell nuclear transfer. The ultimate challenge of cloning procedures is to reprogram the somatic cell nucleus for development of the early embryo. The cell type of choice for reprogramming the somatic nucleus is an enucleated oocyte. Given that somatic cells are easily obtained from adult animals, cultured in the laboratory and then genetically modified, cloning procedures are ideal for introducing specific genetic modifications in farm animals. Genetic modification of farm animals provides a means of studying genes involved in a variety of biological systems and disease processes. Moreover, genetically modified farm animals have created a new form of 'pharming' whereby farm animals serve as bioreactors for production of pharmaceuticals or organ donors. A major limitation of cloning procedures is the extreme inefficiency for producing live offspring. Dolly was the only live offspring produced after 277 attempts. Similar inefficiencies for cloning adult animals of other species have been described by others. Many factors related to cloning procedures and culture environment contribute to the death of clones, both in the embryonic and fetal periods as well as during neonatal life. Extreme inefficiencies of this magnitude, along with the fact that death of the surrogate may occur, continue to raise great concerns with cloning humans.

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Comparison of endoscopic, necropsy and histology scoring of equine gastric ulcers.

Equine gastric ulcer syndrome (EGUS) represents a major health problem in performance horses. Much debate exists regarding endoscopic gastric ulcer scoring systems and their ability accurately to predict severity or depth of gastric ulcers. The purpose of this study was to evaluate the ability of an endoscopist to count gastric ulcers and predict gastric ulcer severity or depth using 2 endoscopic scoring systems and compare them to the same gastric ulcers see on necropsy and histopathology. Endoscopic examination of the stomach was performed under general anaesthesia on 23 mixed breed yearling horses, after feed was withheld for 24 h. Gastric ulcers were scored using 2 systems, number/severity-scoring (N/S) and practitioner simplified (PS) systems. After endoscopy, the horses were subjected to euthanasia and the stomach mucosa examined blindly and scored again at necropsy using above scoring systems. Representative gastric ulcers were then placed in 10% formalin and processed routinely for histopathology. The gastric ulcers were scored using a histopathology system (HSS) based on ulcer depth. Number scores in the N/S scoring system and PS on endoscopic and necropsy examinations were compared using Friedman 2 way analysis of variance. Where significant differences between variables were found a post hoc analysis was conducted using a Tukey's Studentised range (HSD) test. Severity scores using the N/S (ENGS) and PS scores recorded for the stomach via endoscopy and scores from HSS were evaluated for significant association using a Mantel-Haenszel Chi-square and Pearson moment correlation coefficient analysis. Significance was P < 0.05. All horses had gastric ulcers in the nonglandular mucosa via endoscopic examination and at necropsy examination. Mean nonglandular ulcer number (ENGN) score was significantly (P = 0.0024) lower on endoscopic examination compared to the score at necropsy (NNGN); whereas PS scores were not significantly different on endoscopy when compared to necropsy examination. A significant but weak association was found between ENGS and HSS (3.89, P = 0.048; r = 0.453, P = 0.045) and no correlation was found between PS and HSS (1.2, P = 0.272; r = 0.117; P = 0.622). Only 1/23 horses had glandular ulcers observed via endoscopic examination whereas, 6/23 horses had glandular ulcers at necropsy and on histopathology. The prevalence of EGUS is high in stalled yearling horses. The endoscopist may underestimate the number of gastric ulcers and may not be able accurately to predict the severity or depth of those ulcers present in the nonglandular equine stomach. Furthermore, the endoscopist may miss glandular gastric ulcers.

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Transcatheter modification of the atrioventricular node in dogs, using radiofrequency energy.

OBJECTIVE: To develop a protocol for reliably inducing atrioventricular (AV) block (ideally first- or second-degree), using radiofrequency energy. DESIGN: An electrosurgical unit was coupled to an ammeter, which was connected to the distal pole of an electrode catheter positioned at the AV node. Control settings had previously been calibrated to the power output in a circuit with a 100-ohm resistance. ANIMALS: 10 clinically normal dogs. PROCEDURE: Transcatheter AV nodal modification was attempted, using progressive power applications of 10 to 20 W for progressive durations of 10 to 30 seconds. Atrioventricular nodal conduction and refractivity were measured before and 20 minutes and 1 month after ablation. Electrocardiograms were monitored throughout the 1-month period. RESULTS: Eight of the 10 dogs developed complete AV block, I developed stable 2:1 AV block, and another had no long-term change in AV nodal conduction. Four dogs attained their maximal degree of AV block in 2 to 5 days. Three of these had no AV nodal conduction changes until 2 to 4 days after ablation. CONCLUSIONS: An electrosurgical unit can be economically modified for radiofrequency transcatheter ablation. Stable, incomplete AV block was rarely induced using this protocol, whereas complete AV block often developed. A major finding was frequent delay between energy delivery to the AV nodal region and induction of AV block. CLINICAL RELEVANCE: Induction of complete AV block using this technique, followed by permanent pacemaker placement, is an effective alternative to long-term antiarrhythmic treatment in animals with chronic atrial arrhythmias. Transcatheter ablation could be used to treat other forms of tachycardia, as it is in human medicine.

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Pulmonary arterial changes in feline dirofilariasis.

Eleven cats with spontaneous dirofilariasis were necropsied; ten were domestic shorthairs and one was a Persian. The cats ranged in age from 1 to 10 years, and 6/11 cats were male. One to three heartworms were present in the right ventricle and pulmonary arteries of each of the 11 cats. Patchy areas of rugose thickening of the intima of the pulmonary trunk and marked villous endarteritis of lobar and medium-sized pulmonary arteries were observed. Affected larger vessels were partially occluded by large villous intimal proliferations that were lined by hyperplastic endothelial cells supported by connective tissue stroma. Moderate to marked infiltration of eosinophils and mononuclear inflammatory cells was consistently observed in the intima of affected larger pulmonary arteries. Thrombosis of pulmonary arteries was seen in five cats. Medial hypertrophy, mild intimal proliferative changes, and focal infiltrations of leukocytes were seen in small pulmonary arteries. Lesions indicative of right-sided heart failure consisting of right ventricular dilation and chronic passive congestion of the liver were observed in four cats.

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Epididymal swelling attributable to generalized lymphosarcoma in a stallion.

Aspermia was diagnosed in a 12-year-old Thoroughbred stallion with generalized lymphosarcoma. Invasion of the epididymus by neoplastic cells caused thickening and enlargement of both epididymes. The testes were not affected. The nodular ultrasonographic architecture was similar to that in previously reported cases of infectious epididymitis.

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Primary jejunal osteosarcoma associated with a surgical sponge in a dog.

Primary jejunal osteosarcoma was diagnosed in association with a surgical sponge in a dog. The tumor was biologically aggressive, resulting in widespread metastasis throughout the abdomen within 2 months of surgical resection. Microscopic examination of the resected osteosarcoma revealed strands of gauze material throughout the tumor mass. It was theorized that the presence of a sponge foreign body may have resulted in malignant transformation of adjacent tissues similar to what has been reported to occur after internal fixation of some long-bone fractures.

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Induction of pulmonary antibodies to Pasteurella haemolytica following intraduodenal stimulation of the gut-associated lymphatic tissue in cattle.

The induction of pulmonary antibodies to a bacterial antigen following intraduodenal (D) stimulation of the gut-associated lymphatic tissue (GALT) was investigated. Six calves were divided into two groups of three calves each. The GALT-primed calves received an ID dose of live Pasteurella haemolytica A1 followed by a subcutaneous (SC) dose of killed P. haemolytica. The sham-primed calves received an ID dose of phosphate-buffered saline solution (PBSS) followed by a SC dose of killed bacteria. Serum and pulmonary lavage fluids were collected weekly from each calf and assayed for titers of leukotoxin neutralizing antibodies (LNA), as well as IgG and IgA (lavage fluids only) to P. haemolytica. The GALT-primed calves responded to the ID stimulation by bacteria with increased serum IgG. The sham-primed calves had no change in antibody titers following ID stimulation. The GALT-primed calves had increased serum IgG, lavage IgG and IgA and increased LNA titers in both lavage fluids and serum following the SC dose of killed bacteria. The sham-primed calves demonstrated only an increase in serum IgG following the SC inoculation. A challenge study to evaluate if antibodies induced by GALT stimulation could reduce pulmonary lesions was performed using six calves divided into two groups. One group received an ID dose of P. haemolytica followed two weeks later by a SC dose of killed P. haemolytica. The sham vaccinated calves received an ID dose of PBSS followed in two weeks by a SC dose of killed bacterin. Calves were challenged by an intrapulmonary dose of live P. haemolytica A1 eleven days after the SC inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hypoglycemia and chronic renal failure in a cat.

Spontaneous hypoglycemia developed in a 9-year-old cat with chronic renal failure. Resulting seizures stopped after intravenous administration of glucose, but the cat died within 10 hours. This case and reports in human beings suggest that hypoglycemia should be considered in any cat with chronic renal failure that experiences sudden deterioration in mental status or begins having seizures.

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Comparison of the pneumopathogenicity of two strains of bovine viral diarrhea virus.

The pneumopathogenicity in calves of 2 strains of bovine viral diarrhea (BVD) virus, isolate 2724 (a noncytopathogenic virus) and isolate 72 (a cytopathogenic virus), was compared. All calves were inoculated endobronchially, using fiberoptic bronchoscopy. Two calves were given Pasteurella haemolytica, 2 calves were given the noncytopathogenic BVD virus, and 2 calves were given cytopathogenic BVD virus. Five calves were inoculated sequentially with BVD virus and, 5 days later, with P haemolytica. Two of these calves were inoculated with the noncytopathogenic BVD virus and the other 3 with the cytopathogenic strain. Both BVD virus strains caused marked respiratory tract disease in the calves sequentially inoculated with P haemolytica and also impaired pulmonary clearance of P haemolytica. However, the effect of the cytopathogenic strain was more severe than the noncytopathogenic strain, indicating that strains of BVD virus may vary in their pneumopathogenicity for calves.

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Changes in leukocyte populations in pulmonary lavage fluids of calves after inhalation of Pasteurella haemolytica.

The distribution of leukocytes in bovine bronchoalveolar lavage fluids was determined in 15 calves at various times after aerosol exposure to Pasteurella haemolytica. For comparison, 10 calves were exposed to aerosols of phosphate-buffered saline solution; 15 calves, to Staphylococcus epidermidis; and 10 calves, to Salmonella typhimurium endotoxin. At 10 minutes after inhalation exposure for each group, the predominant cell type was the macrophage. Macrophages remained the predominant cell type throughout each lavage interval for calves exposed to phosphate-buffered saline solution and Staph epidermidis. For calves exposed to P haemolytica, there was a decrease in the percentage of macrophages detectable by 30 minutes after exposure, with a corresponding increase in the percentage of neutrophils. Sixty minutes after the inhalation exposure to P haemolytica, the percentages of macrophages and neutrophils in the lavage fluid were equal. By 240 minutes after exposure to P haemolytica, greater than 90% of the cells in the lavage fluids was neutrophils. The increase in the percentage of neutrophils in lavage fluids from calves exposed to S typhimurium endotoxin was similar to that seen for the calves exposed to P haemolytica.

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Experimental production of bovine respiratory tract disease with bovine viral diarrhea virus.

Five 6-month-old calves were inoculated with bovine viral diarrhea (BVD) virus (n = 3) or Pasteurella haemolytica (n = 2) endobronchially with a fiberoptic bronchoscope. Five additional calves were inoculated sequentially with BVD virus followed by P haemolytica at a 5-day interval. Blood samples were collected daily from the calves for bacterial isolation. Clinical signs of respiratory tract disease in calves were recorded daily. If the calves survived, they were killed for necropsy 3 or 4 days after inoculation with P haemolytica (or 8 days after inoculation with BVD virus). The extent and nature of pulmonary lesions in the calves were determined, and the lower portion of the respiratory tract (lungs and trachea) was examined for both these organisms. The 3 calves, inoculated with BVD virus only, developed mild clinical signs mainly manifested as fever, nasal discharge, and occasional cough. Approximately 2% to 7% of the total lung capacity of these calves was pneumonic. Mild clinical signs and localized lesions involving about 15% of the lung volume developed in the 2 calves exposed to P haemolytica only. However, severe fibrinopurulent bronchopneumonia and pleuritis involving 40% to 75% of lung volume developed in the 5 calves inoculated sequentially with BVD virus and P haemolytica. The possible role BVD virus may have in bovine respiratory tract disease is discussed.

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Effect of bovine viral diarrhea virus infection on the distribution of infectious bovine rhinotracheitis virus in calves.

Four calves (control animals) were inoculated (by aerosol) with Cooper's strain of infectious bovine rhinotracheitis (IBR) virus given with an ultrasonic nebulizer. Seven other calves (principals) were inoculated (by aerosol) with a noncytopathic strain of bovine viral diarrhea (BVD) virus and 7 days later, with IBR virus. The calves were killed 3 to 8 days after the latter virus was inoculated. Various tissues were collected from the calves during necropsy and assayed for IBR virus. In the control calves, the IBR virus was recovered only from the cranial part of the respiratory tract and, in much lower concentrations, from the caudal part of the respiratory tract. In contrast, the same virus was widely disseminated in most tissues, usually in high concentrations, of the calves first inoculated with BVD virus (principals). These observations indicate that initial BVD virus infection may impair the ability of calves to clear IBR virus from the lungs and to contain the latter virus at the local infection site. The pathogenesis of various forms of IBR virus-induced diseases in calves is discussed.

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Use of fiberoptic bronchoscopy in experimental production of bovine respiratory tract disease.

Fourteen 6-month-old calves were infected with Pasteurella haemolytica or infectious bovine rhinotracheitis (IBR) virus. Four calves were inoculated sequentially with IBR virus followed by P haemolytica at a 5-day interval. Calves were inoculated by allowing them to inhale an aerosol of the organism or by placing an inoculum in the right lung, using fiberoptic bronchoscopy. Clinical signs of infection were recorded, and the calves, if they survived, were killed and necropsied 3 days after inoculation with P haemolytica (or 8 days after inoculation with IBR virus). The extent of pulmonary lesions was determined, and the lower respiratory tract (lungs and lower trachea) was examined for both organisms. Inoculation of the calves by aerosolization with IBR virus alone resulted in mild respiratory tract disease. Mild-to-moderately severe respiratory tract disease developed as a result of sequential inoculations by aerosolization with IBR virus and P haemolytica. However, respiratory tract disease did not develop in calves exposed by aerosol to P haemolytica alone. Large numbers of these organisms were recovered from the lower respiratory tract of the dually inoculated calves, only indicating delayed pulmonary clearance. Mild clinical signs of disease but substantial, though localized, pneumonic lesions developed in calves inoculated with P haemolytica by fiberoptic bronchoscopy. Calves inoculated with IBR virus by the latter procedure developed moderately severe respiratory tract disease involving 25% to 30% of the total lung volume. Lesions occurred mainly in the right lung, but the left lung also had marked lesions in these calves.(ABSTRACT TRUNCATED AT 250 WORDS)

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Death of an African elephant from probable toxemia attributed to chronic pulpitis.

A 31-year-old captive male African elephant (Loxodonta africana) of 5,000-kg body weight died suddenly in ventral recumbency. Lesions seen at necropsy were bilateral purulent pulpitis and periodontitis of both tusks, serous atrophy of coronary groove fat, Grammocephalus cholangitis, myocardial and skeletal lipofuscinosis, and scattered segmental necrosis in the pectoral muscles. Nonhemolytic streptococci, Corynebacterium sp, Peptostreptococcus anaerobius, Fusobacterium nucleatum, and Bacteroides sp, were recovered from the exudate around one or both tusks. We postulated that the elephant died of hypoxia from prolonged ventral recumbency because of weakness and inability to rise secondary to toxemia from bilateral pulpitis and periodontitis.

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