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Biomedical subjects

J M Cullen

Publications and source records attributed to J M Cullen.

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

Hematologic values and plasma and tissue folate concentrations in dogs given phenytoin on a long-term basis.

During earlier investigations of the hepatic effects in dogs of long-term administration of phenytoin alone or in combination with primidone, erythrocytic macrocytosis, neutropenia, neutrophilic hypersegmentation, and thrombocytopenia were observed. Such abnormalities were observed most often in dogs given phenytoin and resembled those known to be attributable to folate deficiency in human beings with epilepsy treated with phenytoin. To pursue the theory that these hematologic aberrations were caused by drug-induced folate deficiency, 12 dogs were given a diet specifically formulated to contain a minimally adequate concentration of folate. After 2 weeks, phenytoin was administered daily (400 mg, PO, q 8 h) to 8 of the 12 dogs for 54 weeks. A CBC, bone marrow aspiration biopsy, and measurement of plasma and RBC folate concentrations were done every 3 weeks. Bone marrow aspirates were examined by transmission electron microscopy after 24 and 36 weeks, and at the end of the treatment period. Hepatic folate concentration was also determined in all dogs before and after treatment. Excretion of formiminoglutamic acid, as a marker of folate deficiency, was measured in all dogs at the end of the study. All dogs remained healthy throughout the treatment phase. Consistent abnormalities were not observed in the blood or bone marrow of treated dogs. Plasma and RBC folate concentrations decreased in control and treated dogs as a result of dietary restriction (P less than or equal to 0.02), and remained stable until the end of the study. The RBC folate content decreased further in treated dogs (P less than or equal to 0.02), although the hepatic folate content was similar in control and treated dogs. Treated dogs did not excrete formiminoglutamic acid more rapidly than did control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Complement resistance in Actinobacillus (Haemophilus) pleuropneumoniae infection of swine.

The possible role of the complement-mediated bactericidal system in protection of swine against contagious pleuropneumonia was investigated. Strains of Actinobacillus (Haemophilus) pleuropneumoniae representing serotypes 2, 3 and 5 were found to be fully resistant to the bactericidal action of porcine serum from precolostral, clinically normal adult, and chronically infected pigs. All strains were also resistant to hyperimmune rabbit serum, but 3 of 4 strains were sensitive to normal human serum. This bactericidal effect was lost when human serum was previously absorbed with the homologous bacteria, indicating that antibody was necessary for killing. Addition of human serum to porcine serum or to absorbed human serum did not restore the bactericidal system. Pretreatment of the bacteria with undiluted heat-treated human serum also failed to sensitize the bacteria to the absorbed serum, indicating that a heat-labile, absorbable factor may have been required for killing of A pleuropneumoniae. None of the strains was sensitized to porcine serum by sublethal treatment with polymyxin B, a treatment that is known to disrupt the integrity of the outer membrane and induce serum sensitivity in gram-negative bacteria. The ability of A pleuropneumoniae to resist complement killing in vitro may reflect a virulence mechanism in vivo that assists bacteria in avoiding the pulmonary defenses of swine and promotes bacterial invasion of the lungs.

Actinobacillus↗
PubMed1989

Idiopathic pleural effusion and pulmonary thromboembolism in a dog with autoimmune hemolytic anemia.

Pleural effusion and pulmonary thromboembolism were diagnosed in a dog with autoimmune hemolytic anemia. Clinical signs of tachypnea, then dyspnea in association with pleural effusion, developed after 10 days of immunosuppressive corticosteroid therapy (greater than 2 mg/kg of body weight/d, PO). The diagnosis of pulmonary thromboembolism was made tentatively on the basis of results of a radionuclide lung perfusion scan and was confirmed by exploratory thoracotomy and lung biopsy. Tachypnea and pleural effusion gradually resolved without specific treatment, and additional episodes of anemia or dyspnea have not been observed. The pathogenesis of these findings was suspected to be related to corticosteroid-induced thrombotic tendencies, persistent thrombocytosis (greater than 800,000 cells/microliters), and vascular injury caused by repeated jugular venous catheterization. Pulmonary thromboembolism should be considered in dogs that develop clinical signs of tachypnea and/or pleural effusion during administration of immunosuppressive dosages of corticosteroids.

Adrenal Cortex Hormones↗
PubMed1989

A sequential histologic and immunohistochemical study of duck hepatitis B virus infection in Pekin ducks.

Twenty-nine Pekin ducks were inoculated with duck hepatitis B virus (DHBV), DHBV-free serum, or saline at 1 day of age. Congenitally DHBV-infected ducks were also studied. Ducks were killed periodically during a 92-week study and examined histologically and immunohistochemically to assess liver and extrahepatic inflammation and to detect and characterize DHBV core antigen tissue distribution. DHBV infection produced an asymptomatic but persistent DHBV viremia in all ducks associated with a mild to moderate transient hepatic inflammation apparent at 3 to 6 weeks post-inoculation and waning afterwards. DHBV core antigen was detected in hepatocyte cytoplasm at 1 week post-inoculation, and by 3 weeks post-inoculation scattered pancreatic acinar and islet cells also contained viral antigen. Small numbers of mononuclear cells in the splenic white pulp also contained viral antigen. Viral antigen persisted in all of these tissues throughout the duration of the experiment. No inflammation or tissue injury was detected in any of the extrahepatic tissues during the course of DHBV infection. One DHBV-injected duck developed a hepatocellular carcinoma at 88 weeks of age. Isolated patches of neoplastic hepatocytes contained cytoplasmic DHBV core antigen. The results of this study indicate that DHBV, like mammalian hepadnavirus, is capable of producing a persistent infection of the liver and several extrahepatic tissues and suggest that persistent infection may be associated with the development of hepatocellular carcinoma.

Animals↗
PubMed1989

Influence of dietary protein, fat or amino acids on the response of weanling swine to aflatoxin B1.

Two experiments were conducted using corn from clean or aflatoxin B1 (AFB1)-contaminated (182 ppb) sources. Weanling pigs (28 d) were fed one of eight dietary treatments arranged in a 2 x 2 x 2 factorial design. In Exp. 1 (192 pigs), treatments varied in corn source (clean or AFB1-contaminated), CP level (18 or 20%) and added fat (0 or 5%). At the end of the 28-d growth trials, plasma samples were obtained. An AFB1 x CP level interaction was detected (P less than .05) for growth rate (ADG), feed intake (FI) and feed/gain ratio (F/G). Feeding AFB1 reduced (P less than .05) ADG (.30 vs .37 kg/d) and FI (.57 vs .66 kg/d) and increased F/G (1.88 vs 1.78) of pigs fed 18% CP diets. Performance of pigs fed 20% CP diets was not altered by AFB1. Adding 5% fat to diets improved (P less than .05) F/G but did not improve ADG of pigs fed AFB1. There was an AFB1 x CP x fat interaction (P less than .05) for plasma cholesterol. Adding fat or increasing the CP level prevented the depression of plasma cholesterol in pigs fed AFB1. In Exp. 2 (96 pigs), all diets contained 18% CP and the treatments varied in corn source (clean or AFB1-contaminated), added L-lysine HCl (0 or .25%) and added DL-methionine (0 or .15%). Feeding AFB1 reduced (P less than .05) ADG of pigs fed the 18% CP diet (.44 vs .50 kg/d) but not of pigs fed diets supplemented with .25% lysine.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxin B1↗
PubMed1989

Transendoscopic neodymium:yttrium aluminum garnet laser irradiation in horses.

A neodymium:yttrium aluminum garnet (Nd:YAG) laser was used to study effects of applying laser irradiation transendoscopically to the corniculate process of the arytenoid cartilage in horses. Dosimetry was established initially in vitro in 10 corniculate cartilages that were irradiated and examined histologically to determine penetration depths at selected power settings. Eleven horses were given xylazine IV and butorphoral tartrate IV, and their left ventricle and corniculate process were irradiated. Six horses had left laryngeal hemiplegia and were euthanatized and necropsied 14 weeks after laser application and evaluation for upper airway stridor. Endoscopy was performed in the 5 other horses; they were euthanatized and necropsied at selected intervals to characterize the healing process. Healing was by second intention and was complete at 14 weeks. Two horses developed buds of granulation tissue along the laser incision, which resolved after a second laser application. Scar tissue formation resulted in left of midline displacement of the dorsal portion of the right corniculate process. The left ventricle healed without complications and was totally ablated. All horses had inspiratory stridor when exercised 14 weeks after laser irradiation.

Animals↗
PubMed1988

Histologic lesions in broiler chicks given cyclopiazonic acid orally.

Cyclopiazonic acid dissolved in corn oil was administered by gavage to broiler chicks (n = 80) daily, from the day of hatching for 23 days. Chicks were assigned to 3 groups (1, 2, or 4 mg of cyclopiazonic acid/kg of body weight); a control group was given corn oil. Each group was composed of 10 male and 10 female chicks. Surviving chicks were euthanatized and necropsied on day 24. Histologic examination revealed that the most common lesions consisted of necrosis and hemorrhage or hyperplasia of the mucosa of the proventriculus and hepatocellular vacuolation. Skeletal muscle degeneration, characterized by myofiber swelling or fragmentation accompanied by an infiltrate of macrophages and heterophils, was detected in the group given 4 mg/kg. This degeneration was associated with an increase of plasma creatine kinase activity. Focal hepatocellular and splenic necrosis also developed in the groups given 4 mg/kg.

Administration, Oral↗
PubMed1987

Carcinogenicity of dietary aflatoxin M1 in male Fischer rats compared to aflatoxin B1.

Aflatoxin M1 (AFM), an hydroxy metabolite of the potent carcinogenic mycotoxin aflatoxin B1 (AFB) is frequently found in milk and other dairy products. Sufficient amounts of AFM were produced to study the carcinogenicity of this compound. AFM was fed to male Fischer rats starting at 7 weeks up to 21 months of age. Agar-based semisynthetic diets contained 0.0, 0.5, 5.0, and 50.0 micrograms/kg of AFM or 50 micrograms/kg of AFB. Hepatocellular carcinomas were detected in two of 37 rats and neoplastic nodules were found in six of 37 rats fed 50 micrograms/kg AFM between 19 and 21 months. No nodules or carcinomas were observed in the lower AFM dose groups. Nineteen of 20 rats fed a diet containing 50 micrograms/kg of AFB developed hepatocellular carcinomas by 19 months of age. Carcinogenic potency of the aflatoxins was reflected by morphometric quantitation of foci detected in hematoxylin and eosin stained sections. Three rats fed the diet containing 50 micrograms/kg AFM developed intestinal carcinomas. None were observed in other groups. Under the conditions of this experiment AFM was found to be a weak hepatic carcinogen compared to AFB and to possess intestinal carcinogenicity.

Aflatoxin B1↗
PubMed1987

Odontogenic tumors in Fischer rats.

The formation of odontogenic tumors in rats is rare unless they are treated with known carcinogens. In this study, male Fischer rats were continuously fed aflatoxins M1, B1, or control diets, then killed at 1, 6, 10, 16, 17, 19 and 21 months. Of the 186 rats fed aflatoxin M1 at 3 concentrations, 12 developed odontogenic tumors; 7 of 63 rats fed an agar-based diet also developed odontogenic tumors in 17-21 months. The purpose of this study is to describe these tumors. All the tumors were located in the upper jaw associated with the incisor teeth. The tumors developed in the periodontal ligament area and were composed mainly of highly cellular fibrous connective tissue. The fibroblastic nuclei were clustered in poorly defined swirls in areas and were evenly scattered in a myxomatous stroma in other areas. Within this tissue were ovoid sometimes coalescing, calcified bodies resembling cementum. Occasional inclusions of solid epithelial cell nests were present. Scattered nests were composed of ovoid epithelial ghost cells. Acellular cementum-like material surrounded many of these nests. An inductive phenomenon was present around occasional epithelial nests. Rare structures composed of globular dentin with irregular tubules were also observed. These tumors caused distortion of the facial areas and disruption of incisor tooth development. No metastatic lesions were noted but other neoplastic lesions occurred in these animals.

Aflatoxin B1↗
PubMed1987

Chronic urinary tract infection in dogs: induction by inoculation with bacteria via percutaneous nephropyelostomy.

Dogs were inoculated via percutaneous nephropyelostomy with bacteria isolated from canine patients with urinary tract infections (4 dogs were inoculated with Escherichia coli, 2 were inoculated with Proteus mirabilis, and 1 was inoculated with coagulase-positive staphylococci). At approximately monthly intervals after bacterial inoculation, bladder urine specimens were collected via antepubic cystocentesis, and renal pelvic urine specimens were collected via percutaneous nephropyelocentesis. Dogs were euthanatized between 89 and 294 days after bacterial inoculation. Extensive microscopic examination was conducted on the urinary tract of each dog. The dogs did not develop any of the common clinical signs of urinary tract infections (ie, increased frequency of urination, fever, craniodorsal abdominal [renal] pain, or malaise). Inflammation in the lower urinary tract of the dogs was more severe than that in the kidneys. Although pyelitis was present, extension into the outer medulla and renal cortex seemed to be confined to nephropyelostomy tracts. The most severe bladder lesion was found in the dog that developed cystic calculi after inoculation with coagulase-positive staphylococci.

Animals↗
PubMed1987

Pathology of experimental Babesia microti infection in the Syrian hamster.

Pathologic changes produced after 4 weeks of infection by Babesia microti in Syrian hamsters are described and compared to babesiosis of humans. Following intraperitoneal inoculation, both intravascular and extravascular hemolysis developed. Up to 70% of red blood cells were parasitized. The principal morphologic abnormalities were an increase in extramedullary hematopoiesis and hyperplasia of the mononuclear phagocytic cells of the red pulp manifested grossly as splenomegaly, marked renal tubular hemosiderosis and hypertrophy of Kupffer cells. The disease was not fatal to any hamsters during the 4 week study. The clinical signs and lesions were less severe than fatal babesiosis of asplenic humans and similar to severe, but nonfatal disease in spleen intact humans. The hamster may serve as an animal model for the studying the pathophysiology of human babesiosis and for studying potential chemotherapeutic agents.

Animals↗
PubMed1986

Neodymium (Nd):YAG laser surgery in the equine larynx: a pilot study.

Laryngeal surgery in the equine is customarily and routinely performed by means of a ventral laryngotomy incision. Such procedures are usually performed under deep general anesthesia with the horse in dorsal recumbency. The objective of this work was to determine the efficacy of an endoscopic approach coupled to a Nd:YAG laser fiber in performing arytenoidectomy. Arytenoidectomy is commonly indicated in the treatment of arytenoid chondritis and in the failure of prosthetic implantation for left laryngeal hemiplegia. This preliminary study was undertaken to determine the feasibility of the endoscopic laser approach to ablate the most difficult of the structures of the larynx, considering tissue structure and density. This procedure was accomplished by using heavy sedation and local anesthesia and was performed in the standing position. This approach appears to be feasible and makes other adjacent structures accessible via the endoscope coupled to a surgical laser. Indications for future pilot applications of laser surgery in the equine larynx are entrapment of the epiglottis, dorsal soft palate displacement, and the ablation of laryngeal cysts and polyps. This pilot study appears to offer a new modality for discrete surgical ablation of this structure, with minimal postoperative complications and a reduced or equivalent convalescent period in this valuable species of animal.

Animals↗
PubMed1985

Relationship of upper and lower urinary tract infection and bacterial invasion of uroepithelium to antibody-coated bacteria test results in female dogs.

Urinary tract infection was demonstrated in 12 female dogs via bacteriologic culture of a specimen of bladder urine collected by antepubic cystocentesis. Escherichia coli was isolated in pure culture from the urine of 9 dogs. Urine specimens from 2 dogs contained E coli and alpha-streptococci and from 1 dog contained Streptococcus zymogenes in pure culture. In 6 dogs, urinary tract infection was limited to the urinary bladder, whereas 6 dogs had unilateral or bilateral culture-positive renal pelvic urine as well (specimens collected by percutaneous nephropyelostomy). An antibody-coated bacteria (ACB) test was conducted on a portion of the bladder urine specimen from each dog, and the urinary tissues from these 12 dogs and from 6 healthy, noninfected female dogs were examined at necropsy. Tissues were given a subjective score based on the severity of the lesions seen microscopically. Histologic scores, bacterial cultural results, and ACB test results were examined for significance. A significant difference was found in the histologic scores between infected and noninfected dogs (P less than 0.025), but comparisons among histologic scores, cultural results, and ACB test results were not significant among infected dogs. The ACB test could neither be used to localize bacterial infection within the urinary tract nor could it be used to indicate the presence of bacterial invasion of the uroepithelium in dogs.

Animals↗
PubMed1985

Cancer risks posed by aflatoxin M1.

The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

Aflatoxin M1↗