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Biomedical subjects

R C Dysko

Publications and source records attributed to R C Dysko.

At least 19 recordsLinked to original sources
PubMed2001

Subcutaneous hemangiosarcomas in a rhesus macaque (Macaca mulatta).

Hemangiosarcoma is a malignant tumor of vascular endothelial cell origin. The occurrence of hemangiosarcoma in nonhuman primates has been rarely documented. An adult male rhesus monkey was reported having a firm subcutaneous swelling, approximately 4.5 cm in diameter, on the ventral midline of the abdomen. Fine-needle aspiration, microbial culture, biopsy, radiographs, exploratory laparotomy, histopathology, immunohistochemistry, hematology, and serology were performed. A second subcutaneous mass approximately 4.5 x 4.0 x 2.7 cm developed on the ventral midline several weeks later. A fine-needle aspirate of the first mass consisted of numerous erythrocytes with few polymorphonuclear cells and lymphocytes. Histopathology showed foci of spindle-shaped cells surrounding the vascular spaces. Many spindle-shaped cells had prominent nucleoli, and mitotic figures could occasionally be seen. Immunohistochemical staining of the masses for Factor VIII-related antigen, an endothelial cell and tumor marker, yielded positive results. Both masses were consistent with hemangiosarcoma.

Abdominal Neoplasms↗
PubMed2000

Altered podocyte structure in GLEPP1 (Ptpro)-deficient mice associated with hypertension and low glomerular filtration rate.

Glomerular epithelial protein 1 (GLEPP1) is a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte. The GLEPP1 gene (PTPRO:) was disrupted at an exon coding for the NH(2)-terminal region by gene targeting in embryonic stem cells. Heterozygote mating produced the expected genotypic ratio of 1:2:1, indicating that the Ptpro(-/-) genotype does not lead to embryonic or neonatal lethality. Kidney and glomerular structure was normal at the gross and light microscopic levels. Scanning and transmission electron microscopy showed that Ptpro(-/-) mice had an amoeboid rather than the typical octopoid structure seen in the wild-type mouse podocyte and that there were blunting and widening of the minor (foot) processes in association with altered distribution of the podocyte intermediate cytoskeletal protein vimentin. Reduced filtration surface area in association with these structural changes was confirmed by finding reduced glomerular nephrin content and reduced glomerular filtration rate in Ptpro(-/-) mice. There was no detectable increase in the urine albumin excretion of Ptpro(-/-) mice. After removal of one or more kidneys, Ptpro(-/-) mice had higher blood pressure than did their wild-type littermates. These data support the conclusion that the GLEPP1 (Ptpro) receptor plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function.

Albumins↗
PubMed1998

Review of exertional rhabdomyolysis and a case in a rhesus monkey (Macaca mulatta).

This is the first confirmed report of exertional rhabdomyolysis in a non-human primate. The monkey was singly housed and presented with anorexia and reluctance to move. There was no external evidence of trauma. Clinicopathologic findings included mild azotemia, marked elevation in serum creatine phosphokinase (CPK), alanine aminotransferase, aspartate aminotransferase, and myoglobinuria. Two days post-incident, the peripheral skeletal muscle had marked multifocal myonecrosis and fibrillar disruption without an inflammatory reaction. Treatment included diuresis and pain relief, and urinary output was monitored. The monkey recovered over the next two weeks. The major significance of skeletal muscle damage is the potential of released myoglobin to cause acute renal failure in the presence of other co-factors such as hypovolemia, acidosis, or ischemia. CPK levels can be highly variable and are inconsistent with the degree of muscle damage; however, CPK is thought to be the most sensitive enzyme marker for muscle necrosis. Because of the potential life-threatening sequelae, exertional rhabdomyolysis should be included as a differential diagnosis when similar clinical and pathological signs are observed.

Alanine Transaminase↗
PubMed1996

Squamous cell carcinoma of the midventral abdominal pad in three gerbils.

Squamous cell carcinoma of the midventral abdominal pad was diagnosed in 3 male gerbils. Two of the gerbils had raised, ulcerated masses on the midventral portion of the abdomen. The first gerbil was 2 years old, and an excisional biopsy was performed. The gerbil survived 23 months after surgery without evidence of metastasis or clinical signs of local recurrence. At necropsy, neoplastic squamous cells were seen on histologic examination of the surgery site. The second gerbil was 4 years old, and surgical excision of the tumor with concurrent castration was curative. The third gerbil was moribund on admission, perhaps because ulceration of the tumor may have allowed bacteria to invade the tissue, resulting in septicemia and disseminated intravascular coagulation. These gerbils illustrated that hematologic, radiographic, and biochemical testing in rodents can be useful and that excision of squamous cell carcinoma tumors of the midventral abdominal pad of gerbils can be an effective treatment.

Abdominal Muscles↗
PubMed1996

Oxytetracycline-induced nephrotoxicosis in dogs after intravenous administration for experimental bone labeling.

Tetracyclines have been used as in vivo indicators of new bone formation because they form complexes with mineral at bone-forming surfaces. Four of 12 dogs in a bone-labeling study developed clinical signs of renal disease (vomiting, diarrhea, dehydration, and azotemia) within 1 to 2 days of receiving oxytetracycline at a bone-labeling dose of 25 mg/kg of body weight, once daily for 2 consecutive days. To delineate the relationship between oxytetracycline administration and renal damage, six dogs were given the bone-labeling dose intravenously and were subsequently evaluated by determination of clinical signs, serum biochemical analysis, urinalysis, and histologic examination (experiment 1). Drug administration was modified in the five dogs remaining in the bone-labeling orthopedic study. These dogs received the oxytetracycline dose as a slow intravenous infusion diluted with 250 ml of lactated Ringer's solution (experiment 2). All six dogs of experiment 1 developed persistent isosthenuria within 2 days of receiving the bone-labeling dose of oxytetracycline. Clinical illness (three of six dogs) was associated with azotemia, creatinemia, and hyperphosphatemia. All dogs had multifocal, mild to moderate flattening of renal tubular epithelium, characteristic of nephrosis. None of the dogs of experiment 2 developed any clinical indications of renal disease, and the only biochemical abnormality was isosthenuria in two of the five dogs. Thus the development of clinical signs and biochemical abnormalities associated with the intravenous administration of oxytetracycline was obviated by the slow administration of a dilution of the calculated bone-labeling dose of the antibiotic.

Animals↗
PubMed1994

Accelerated myocardial relaxation in conscious dogs during acute cardiac tamponade.

Eight chronically instrumented conscious dogs were used to test the hypothesis that left ventricular (LV) relaxation is accelerated during cardiac tamponade. The time constant of LV transmural pressure fall was measured before and during intrapericardial (IP) saline infusion (baseline) with and without beta-adrenergic blockade (propranolol 1 mg/kg iv). Heart rate was controlled by atrial pacing. Increasing IP pressure caused a progressive linear decrease in stroke volume before and during beta-blockade in each animal. The time constant of LV transmural pressure fall also decreased continuously with an increase in IP pressure from 26 +/- 7 ms during baseline to 18 +/- 5 ms during severe cardiac tamponade (P < 0.01) before beta-blockade. However, after beta-blockade, the time constant of LV transmural pressure fall was constant over a wide range of IP pressures despite a continuous decrease in LV end-diastolic volume. The time constant of LV transmural pressure fall was not altered by vena caval occlusions that caused the same decrease in LV preload observed during cardiac tamponade. We concluded that despite decreased pump function, LV relaxation was accelerated progressively during graded cardiac tamponade, and this change was dependent not on changes in loading conditions but on an intact beta-adrenergic influence.

Acute Disease↗
PubMed1994

Immune complex vasculitis with secondary ulcerative dermatitis in aged C57BL/6NNia mice.

A spontaneous, severely pruritic ulcerative dermatitis was initially observed in 33/201 (16.4%) aged C57BL/6NNia mice obtained from the National Institute of Aging. This ulcerative dermatitis also developed in 21/98 (21%) aged C57BL/6 mice in a subsequent experimental group obtained from the same source. The average age of onset in the initial group was 20 months. These animals were negative for ectoparasite infestation and primary bacterial or fungal infection. The lesions varied from acute epidermal excoriation and ulceration to chronic ulceration with marked dermal fibrosis. In the affected animals, leukocytoclastic vasculitis was present in the dermis in both areas of ulceration and areas covered by normal intact epidermis. Immunofluorescent staining of the skin was positive for deposition of IgG, IgM, and fibrinogen in the dermal vessels of the affected mice. Leukocytoclastic vasculitis was not observed in unaffected animals, nor were deposits of immunoglobulin or fibrinogen present in the skin of the control animals. This study provides strong evidence that the ulcerative dermatitis is caused by an immune complex-induced vasculitis. The elucidation of the pathogenesis of this disease is important because of the significant percentage of animals affected and because the C57BL/6 mouse may be a useful model to study human vasculitides.

Age Factors↗
PubMed1994

Sedative efficacy of droperidol and diazepam in the rat.

Droperidol and diazepam were evaluated for sedative properties in 12 male Sprague Dawley rats (Rattus norvegicus). Over a period of several weeks, each rat was treated subcutaneously with 0.5 mg droperidol/kg, 2.0 mg droperidol/kg, 5.0 mg diazepam/kg, 15.0 mg diazepam/kg, and physiologic saline according to a randomized schedule. After each treatment, the animals were evaluated for their response to a series of four common clinical manipulations (tail-vein bleeding, orbital bleeding, teeth clipping, and toenail bleeding) at five time points over the 90 min following the injection. Rats were scored on the basis of their responses to each manipulation. Response to cardiac puncture was assessed once in each animal immediately prior to euthanasia. Histologic lesions associated with subcutaneous and intramuscular administration of these drugs were evaluated in a separate group of animals. Results indicate that both droperidol and diazepam (at either dose) allow easier manipulation for toenail bleeding and teeth clipping when compared with saline control. There was no advantage in using these sedatives for tail-vein bleeding. Orbital bleeding could not be performed humanely with either drug. Diazepam at a dose of 15.0 mg/kg allowed humane cardiac puncture. Subcutaneous injection of diazepam or 2.0 mg droperidol/kg resulted in various degrees of inflammation revealed by histologic examination, although no clinical signs were associated with these lesions. Subcutaneous administration of droperidol at a dose of 0.5 mg/kg is recommended for nonpainful, noninvasive manipulations as it provides adequate sedation for most procedures without inducing the subcutaneous inflammation observed with diazepam or 2.0 mg droperidol/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Welfare↗
PubMed1992

EDTA reduces liver cholesterol content in cholesterol-fed rabbits.

A study conducted in 1953 by one of the authors (H.S.M. Uhl) reported that orally administered ethylenediamine tetraacetic acid (EDTA) both prevented the accumulation of cholesterol in the liver of cholesterol-fed rabbits and caused the removal of accumulated cholesterol from the liver. These observations were made in rabbits fed high concentrations of cholesterol and have never been confirmed in the literature. The purpose of the present study was to determine if this original observation could be confirmed using lower amounts of dietary cholesterol and more modern and comprehensive methods for analysis of tissue lipids and plasma lipoproteins. New Zealand White rabbits were fed diets containing 0.1% cholesterol with or without EDTA (3 g/day). After 16 weeks, significantly lower concentrations of hepatic cholesterol were found in rabbits fed EDTA (6.95 mg/g wet weight) compared with controls fed the same cholesterol-containing diet without EDTA (16.6 mg/g wet weight). Plasma cholesterol levels in both groups of animals were not significantly different from one another; therefore, the effect of EDTA in reducing liver cholesterol accumulation was independent of changes in plasma cholesterol concentrations. Although the mechanism of this EDTA effect is unknown, it may provide a tool to gain further insight into mechanisms of regulation of hepatic lipoprotein and cholesterol metabolism.

Animals↗
PubMed1991

Partial lobectomy via a ligature fracture technique: a method for multiple hepatic biopsies in nonhuman primates.

A ligature fracture technique was used to obtain multiple large (2 to 4 g) liver biopsy samples in both African green and cynomolgus monkeys. The technique was performed 195 times in 84 animals using three different surgical approaches, with no associated illness or mortality. In a subset of 18 animals, a slight decline in hematocrit percentage was noted during 14 days postsurgery (44.6 to 39.4%), but total plasma protein remained unchanged (5.98 to 5.95 g/dl). Serum alanine aminotransferase concentrations rose to 178.11 U/l at day 1 postoperatively, from a baseline value of 93.61 U/l. This elevation was transient, however, and declined to 49.65 U/l by day 14. Our experience has shown that the partial lobectomy via the ligature fracture technique is a safe and effective means to obtain multiple large samples of liver in nonhuman primates.

Alanine Transaminase↗
PubMed1989

Regulation of blood flow to the rabbit corpus luteum: effects of estradiol and human chorionic gonadotropin.

We tested the hypothesis that estrogen and hCG can modify blood flow in the rabbit corpus luteum. Radioactively labeled microspheres were used to measure luteal blood flow in pseudopregnant rabbits in which estrogen had been withdrawn to initiate premature luteal regression and in pseudopregnant rabbits injected with hCG. Removal of estradiol-filled Silastic capsules on day 10 of pseudopregnancy caused an 80% decrease in the serum progesterone concentration within 24 h. Despite the decline in progesterone secretion, luteal blood flow remained at very high levels and was not different from that in control rabbits treated continuously with estradiol. Replacement of estradiol-filled capsules for 3 h did not change the high rate of blood flow to the corpus luteum, but blood flow in the uterus, vagina, and ovarian stroma was increased. The injection of hCG (10 IU, iv) on day 10 of pseudopregnancy caused a 3-fold increase in blood flow to the nonluteal portion of the ovary and a 3-fold increase in the serum progesterone concentration, but luteal blood flow did not change. We conclude that the acute actions of estradiol or hCG in the rabbit corpus luteum are not mediated by changes in luteal blood flow. Further, the results suggest that the luteal vasculature is regulated differently from the vasculature of other estrogen-responsive tissues and that blood flow in the nonluteal tissues of the ovary can be regulated independently of blood flow in the corpus luteum.

Animals↗
PubMed1988

A reversible pulmonary artery band: preliminary experience.

Pulmonary artery banding has become an infrequently used surgical technique. However, if a band was developed that could be relieved without the need for open heart surgery, it is likely that pulmonary artery banding would be used more frequently in the management of infants with congenital heart disease. Such a pulmonary artery band was placed in seven 1 week old mongrel puppies by using a loop of an absorbable suture material (Vicryl). One dog died at 2 months as a result of right ventricular failure. The remaining six dogs underwent cardiac catheterization and pulmonary balloon angioplasty at 6 months of age. After measuring pulmonary artery, right ventricular and aortic pressures and performing a right ventricular angiogram, balloon angioplasty of the band site was performed. A 20 mm balloon angioplasty catheter (Medi-Tech) was used in all dogs. Balloon angioplasty decreased right ventricular pressure from 101 +/- 19 to 42 +/- 3 mm Hg (p less than 0.05) and right ventricular systolic outflow tract gradient from 59 +/- 14 to 7 +/- 2 mm Hg (p less than 0.03), and increased the size of the band site from 8.7 +/- 0.03 to 14.9 +/- 0.5 mm (p less than 0.01). All dogs were recatheterized 2 months after angioplasty and were then killed for pathologic evaluation. At follow-up catheterization, right ventricular pressure, right ventricular outflow tract gradient and pulmonary artery size at the band site remained at the values obtained immediately after angioplasty. Postmortem examination demonstrated that there was no evidence of pulmonary artery damage. Although these studies are preliminary, they suggest that a reversible pulmonary artery band can be performed.

Angioplasty, Balloon↗
PubMed1988

Protection of reperfused ischemic canine myocardium by CI-922, a new inhibitor of leukocyte activation.

There is increasing evidence that activated neutrophils cause myocardial injury during reperfusion of ischemic myocardium. This study was performed to assess the effect of Ci-922, an inhibitor of neutrophil activation, in a canine preparation of myocardial infarction. Dogs received 15-min infusions of CI-922 1 mg/kg or 5% dextrose beginning 30 min before occlusion of the left circumflex coronary artery. After occlusion for 90 min and reperfusion for 6 h, infarct size was determined by ex vivo perfusion of the left circumflex coronary artery with triphenyltetrazolium chloride. The percentage of the area at risk infarcted was: control, 42 +/- 5; and CI-922, 23 +/- 4 (p less than 0.05 vs. control). There were no significant inter-group differences in heart rate or mean arterial pressure, and CI-922 did not enhance collateral blood flow to the ischemic bed. After incubation with CI-922 (100 microM), production of superoxide anions by canine neutrophils activated by opsonized zymosam decreased from 3.5 +/- 0.2 to 2.0 +/- 0.4 nmol/10 min/10(6) cells (p less than 0.05). Thus, inhibition of neutrophil-mediated damage may explain the cardioprotective effect of CI-922.

Animals↗
PubMed1988

Total and regional blood flows in vascularized skeletal muscle grafts in rabbits.

The transplantation of whole skeletal muscles is a common clinical procedure. Although atypical blood flows have been reported in small free muscle grafts, the blood flow of large neurovascular-intact (NVI) and neurovascular-anastomosed (NVA) grafts have not been measured. Because the maximum specific force (N/cm2) of NVI and NVA grafts is 65% that of control muscles, we hypothesized that total and regional blood flows (ml.min-1.100g-1) of NVI and NVA grafts at rest and during twitch contractions are significantly lower than lower flows of control muscles. In rabbits, blood flows of control rectus femoris (RFM) muscles and NVI and NVA grafts of RFM muscles were measured by the radioactive-microsphere technique. In control muscles, blood flow increased linearly from 6.8 +/- 1 ml.min-1.100 g-1 at rest to 64.4 +/- 7 ml.min-1. 100 g-1 at a stimulation frequency of 3 Hz with no further increase at 4 Hz. Total blood flows in grafts were not different from the control RFM muscle values, except for a higher resting flow in NVA grafts and a lower flow at 3 Hz in NVI grafts. Minor variations in regional flows were observed. We conclude that the operative procedures of grafting and repair of blood vessels affect the vascular bed of muscles minimally, and the deficits observed in grafts do not arise from inadequate perfusion.

Animals↗