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Biomedical subjects

R M Lewis

Publications and source records attributed to R M Lewis.

At least 181 records · Page 10Linked to original sources

Comparative effects of age and sedation on sinus node automaticity and atrioventricular conduction.

Corrected sinus node recovery time (CSNRT) and atrioventricular node effective refractory period are longer in nonsedated adults than in sedated children at cardiac catheterization. We attempted to ascertain the relative contributions of age and catheterization sedation on these differences by studying adult beagles and beagle puppies previously instrumented with atrial pacing wires. We found that CSNRT was similar in adults and puppies prior to drug administration. CSNRT shortened significantly after meperidine, promethazine, and chlorpromazine (DPT) administration in both adult dogs and puppies. Atrioventricular node effective refractory period (AVERP) was shorter in puppies than adults prior to DPT, and did not shorten in in either group after DPT. These findings suggest that the difference between CSNRTs in children and adults can be at least partly explained by the sedation used in children. This is an important consideration when premedicating children for electrophysiologic studies, particularly in children with suspected sinus node dysfunction.

Aging↗

Microspheres in cardiac lymph: control and ischemic states.

The cardiac lymph from conscious animals was monitored for the presence or absence of radiolabelled 15 micrometer microspheres during: 1) control periods after left atrial injection of microspheres and b) after circumflex coronary artery (CFX) occlusions (10--20 min total or less than 40 mins 50% of control flow) followed by full reperfusions. Microspheres (15 mu) numbering 7--150 were present in the lymph within 2 hrs after the occlusions; and in three experiments, the presence of a small number in the lymph on the following day implied continual release overnight. No microspheres were present in 8--48 hr lymph samples prior to occlusions. This study suggests that some microspheres escape from the intravascular space of the myocardium and are channeled into the cardiac lymphatics; this is apparent even after short-term ischemic events.

Animals↗

The comparative hemodynamic effects of isoproterenol in chronically instrumented puppies and adult dogs.

Although isoproterenol is the sympathomimetic amine used most often to augment cardiovascular function in infants and children, little is known about the hemodynamic effects of this drug on the immature cardiovascular system. To compare the hemodynamic effect of isoproterenol in the young animal with that in the mature animal, we infused the drug into 11 puppies of 12-38 days of age, 12 puppies of 56-89 days of age and 10 adult beagle dogs. The animals were chronically instrumented and nonsedated during the study. Isoproterenol was infused in doses of 0.05, 0.125, 0.25 and 0.5 microgram/kg/min. Isoproterenol decreased systemic arterial mean blood pressure, increased heart rate and had no effect on renal blood flow in all three groups of animals. While cardiac output was increased and systemic vascular resistance decreased in the adult dogs, neither changed in puppies. Stroke volume increased slightly in adult dogs, but decreased in puppies. This refractoriness to change of cardiac output in immature dogs may be a function of elevated resting cardiac output, developmental changes of contractility or ventricular compliance or developmental changes of vascular smooth muscle responsiveness.

Aging↗

Urinary protein excretion and immunopathologic findings in dogs with glomerular disease.

Clinical and histopathologic findings in 21 dogs with glomerular disease were reviewed. Diagnoses included amyloidosis, glomerulonephritis, and secondary glomerular atrophy. Dogs with amyloidosis excreted the largest amount of urinary protein per day, and 5 of 6 so affected had clinical signs of advanced renal disease at the time of examination. Dogs with glomerulonephritis excreted significantly less urinary protein per day, and none had clinical signs of advanced renal disease at the time of examination. The magnitude of proteinuria was correlated more with the nature of the glomerular lesion than with the stage of renal disease.

Amyloidosis↗

An epidemiologic study of households exposed to canine systemic lupus erythematosus.

To determine whether exposure to canine lupus is a risk for human lupus, we studied 83 members of 23 households exposed to 19 dogs with high titer antinuclear antibodies and compared these contact households to 50 members of 18 control households matched for dog age, sex, and primary veterinarian. No differences were found between contacts and controls in titer of antinuclear, antiDNA, antiRNA, and antilymphocyte antibodies, frequency of positive rheumatoid factor, or elevated serum immunoglobulins. Further analysis of subgroups by age, sex, and intensity of dog exposure did not reveal any serologic differences between contacts and controls. No cases of lupus were identified in either group. Three contact households and no controls reported a family history (remote from the household) of lupus. This study did not detect any clinical or serologic effect of human household exposure to dogs with high titer antinuclear antibodies.

Adolescent↗

Biochemical studies of the excitable membrane of Paramecium. IV. Protein kinase activities of cilia and ciliary membrane.

Two protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) were detected in disrupted cilia of Paramecium tetraurelia. One of the enzymes exhibited maximum activity at pH 6.0, required 4 mM Mg2+ for its maximum activity and was stimulated by cyclic AMP and cyclic GMP. Histone was a good exogenous protein substrate for this enzyme, but protamine sulfate was not. The other protein kinase showed a peak of activity at pH 8.0, required 10 mM Mg2+ for its maximum activity and was slightly inhibited by cyclic AMP and cyclic GMP. Protamine sulfate was a good exogenous substrate for this enzyme. The pH 8.0 activity partitioned preferentially with the axonemes, but the pH 6.0 activity was divided almost equally between the axonemes and the membranes. We also found indirect evidence for the presence in cilia of phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) and adenyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity.

Adenosine Triphosphate↗

Moderate, rapidly induced hypertension as a cause of intraventricular hemorrhage in the newborn beagle model.

Nine anesthetized, artificially ventilated, term newborn beagle puppies were given phenylephrine hydrochloride intravenously while systemic arterial, carotid arterial, and jugular venous blood pressures, and carotid arterial blood flow were monitored. Systemic blood pressure rose within seconds from a mean of 53.68 +/- 1.10 mm Hg to a mean of 81.92 +/- 5.14 mm Hg. Hypertension was maintained for up to one hour in each animal. Four of the nine pups had intraventricular hemorrhages that were visible to gross inspection at autopsy, and seven of the nine pups had subependymal hemorrhages. The blood pressures produced in these animals were within the range of those seen in premature infants. Thus, moderate, rapidly induced systemic hypertension may be a cause of intraventricular hemorrhage in the premature human newborn infant.

Animals↗

Biochemical studies of the excitable membrane of Paramecium tetraurelia. III. Proteins of cilia and ciliary membranes.

As a first step in the biochemical analysis of membrane excitation in wild-type Paramecium and its behavioral mutants we have defined the protein composition of the ciliary membrane of wild-type cells. The techniques for the isolation of cilia and ciliary membrane vesicles were refined. Membranes of high purity and integrity were obtained without the use of detergents. The fractions were characterized by electron microscopy, and the proteins of whole cilia, axonemes, and ciliary membrane vesicles were resolved by SDS polyacrylamide gel electrophoresis and isoelectric focusing in one and two dimensions. Protein patterns and EM appearance of the fractions were highly reproducible. Over 200 polypeptides were present in isolated cilia, most of which were recovered in the axonemal fraction. Trichocysts, which were sometimes present as a minor contaminant in ciliary preparations, were composed of a very distinct set of over 30 polypeptides of mol wt 11,000--19,000. Membrane vesicles contained up to 70 polypeptides of mol wt 15,000--250,000. The major vesicle species were a high molecular weight protein (the "immobilization antigen") and a group of acidic proteins with mol wt similar to or approximately 40,000. These and several other membrane proteins were specifically decreased or totally absent in the axoneme fraction. Tubulin, the major axonemal species, occurred only in trace amounts in isolated vesicles; the same was true for Tetrahymena ciliary membranes prepared by the methods described in this paper. A protein of mol wt 31,000, pI 6.8, was virtually absent in vesicles prepared from cells in exponential growth phase, but became prominent early in stationary phase in good correlation with cellular mating reactivity. This detailed characterization will provide the basis for comparison of the ciliary proteins of wild-type and behavioral mutants and for analysis of topography and function of membrane proteins. It will also be useful in future studies of trichocysts and mating reactions.

Animals↗

Intraventricular hemorrhage--an animal model.

Hemodynamic monitoring was carried out in 9 newborn beagle puppies exposed to hypercarbic insult. 4 animals were exposed to slowly increasing carbon dioxide tensions without hypoxemia; 5 animals were exposed to rapid, intense increase in carbon dioxide tensions without hypoxemia. 2 of the 5 puppies (40%) exposed to the rapid hypercarbia developed intraventricular hemorrhage characteristic of that found in the immature human. All of the puppies exhibited germinal matrix layers comparable to those of 30- to 32-week gestational age human infants. Significantly higher systemic arterial and jugular venous pressures were documented during the baseline and experimental periods in the 2 animals that bled. A predisposition to hemorrhage may have been present in these 2 animals because of hypertension in the baseline period. This preliminary study demonstrates that a histological model for IVH exists in an animal which is stable enough for extensive hemodynamic monitoring.

Animals↗

The comparative pathology of non-viral bullous skin diseases in domestic animals.

In a review of non-viral bullous skin diseases of domestic animals and a 4-year study of cases presented to the New York State College of Veterinary Medicine, we found 15 diseases: pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus, bullous pemphigoid, systemic lupus erythematosus, dermatitis herpetiformis, toxic epidermal necrolysis, drug eruption, epidermolysis bullosa, epidermolysis bullosa simplex, familial acantholysis, bovine congenital porphyria, impetigo and subcorneal pustular dermatosis. The 15 diseases were placed in five categories: autoimmune, immune-mediated, hereditary, bacterial and idiopathic. A histologic classification of these disorders based on the site of blister formation and other important clinicopathologic, histologic and immunopathologic findings was developed.

Acantholysis↗

Detection of factor IX antibodies by radioimmunoassay: effect of calcium on antibody-factor IX interaction.

A radioimmunoassay for alloantibodies (inhibitors) and heteroantibodies to human factor IX has been developed using radioiodinated human factor IX and formalin-fixed, heat-killed Staphylococcus aureus cells (Staph A). Staph A was used as a solid-phase adsorbent for immune complexes. The assay is specific, shows excellent correlation with factor IX coagulant neutralization assays in detecting alloantibodies (r = 0.98), and is 60 times more sensitive. The Staph A method allows rapid separation of immune complexes (within 10 min of addition) and binds immunoglobulin with equivalent efficiency in the presence and absence of calcium. These characteristics have made the Staph A binding method useful for observing the Ca++ effect on the antigenicity of factor IX as detected by hetero- and alloantibodies. All antisera investigated showed some increase in antibody titer when measured in the presence of Ca++. One particular alloantibody showed the greatest increase in titer (> twofold). The reversibility of the calcium effect by excess EDTA indicates that it was not caused by Ca++-dependent proteolysis of the factor IX molecule. The Staph A procedure can also be used as a sensitive competitive radioimmunoassay for human factor IX using alloantibody. The assay could detect factor IX antigen to a dilution of 1:1280 of normal plasma and correctly classified hemophilia B plasmas as cross-reacting material positive or negative.

Antibodies↗

Cardiac lymph flow in conscious dogs.

The cardiac lymphatic duct was cannulated in dogs and the exteriorized cannula allowed chronic collection of lymph during the awake state for as long as 3 wk. The surgical methodology and inherent difficulties in the technique are describ:d. Cardiac lymph flow ranged from 0.45--5.6 ml/h in the control state in 14 dogs. An occluding device and flow probe were placed on the circumflex coronary artery (CFX); ultrasonic segment length crystals were placed in the left ventricular free wall in 4 dogs. Occlusion of the CFX in these conscious dogs caused lymph flow to fall as great as 46% below control during the 1st half-hour. Reperfusion of the occluded vessel caused an increase in lymph flow as great as 67% above control. The effect on cardiac lymph flow was demonstrated for a few select drugs that have known effects on the cardiovascular system. Cardiac lymph flow was altered from control as follows: isoproterenol, 42 +/- 11% increase; RO 2-2985, 118 +/- 8% increase; verapamil, 101 +/- 10% increase; propranolol caused no significant change. The conscious dog with cardiac lymph vessel cannulated should provide a model to further study the complexities of cardiac metabolism and physiology without interference of anesthesia and surgical stress.

Animals↗

Permanent changes of ventricular contractility and compliance in chronic volume overload.

Left ventricular volume overload (LVVO) has been created in 18 dogs by anastomosing a Dacron conduit between the infrarenal abdominal aorta and inferior vena cava. The dogs previously were instrumented so that in the awake state LV pressure, systemic arterial pressure, LV dP/dt, myocardial segment length and excursion, and coronary and renal artery velocities could be monitored. The animals were stressed with separate infusions of alpha-adrenergic and beta-adrenergic agonists. Both at rest and with stress, over a 12-wk period, preejection, ejection, and contractility indices decreased. Left ventricular compliance decreased as exemplified by the increased ratio of end-diastolic pressure to end-diastolic length. The shunt was ablated in 7 dogs, and monitoring in conjuction with alpha- and beta-adrenergic stress foan additional 12 wk demonstrated an initial improvement in the previous indices. However, the amelioration plateaued and values similar to the control state were not attained. This suggests that potentially permanent alterations in ventricular function and compliance have occurred.

Adrenergic alpha-Agonists↗

Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog. IV. Energy mechanisms during very early ischemia.

Tissue energy metabolism was examined in posterior (ischemic) and anterior ("control") regions of canine ventricles after 5 and 10 minutes of left circumflex coronary artery occlusion. When compared to identical regions of normal hearts, the following changes were found: (1) decreases in glycogen and phosphorylase activity in the anterior and posterior regions, (2) depressed state 3 rates of oxygen consumption of isolated mitochondria in both anterior and posterior regions, (3) shifts in optimum substrate concentrations for palmityl-CoA (+ carnitine) oxidation by mitochondria in the anterior and posterior regions, and (4) decreases in the apparent zero order and first order rates of mitochondrial palmitylcarnitine production. These changes correlated with a marked decrease in developed tension in the posterior regions. Depression in tension development in the posterior regions of the heart still was present after 30--60 minutes of reperfusion following a 10-minute period of occlusion. Glycogen content in the reperfused areas was significantly decreased after 60 minutes of reperfusion when compared to normal areas and to control hearts perfused for 70 minutes. After reperfusion, mitochondrial function appeared to return toward "normal." However, the slow restoration of contraction of the ischemic area suggests that cellular mechanisms operative in vivo to restore pump function still might be abnormal.

Acyl Coenzyme A↗

Comparative pathology of glomerulonephritis in animals.

Glomerulonephritis constitutes an important category of renal diseases in animals and has been recognized with increasing frequency in the last decade. We report here the comparative morphologic aspects of glomerulonephritis as a naturally occurring disease of animals. We briefly review the immunopathogenesis of glomerulonephritis. The morphology of renal lesions occurring in glomerulonephritis in dogs, cats, cattle, sheep, horses and swine has been reviewed with emphasis on the range and specificity of various glomerular lesions and on the comparison of lesions between various species. A distinction was made between glomerulonephritis as a primary disease entity and glomerulonephritis associated with other disease processes. Primary idiopathic glomerulonephritis occurred in all species but was most commonly recognized as a clinically important disease in dogs and cats. Glomerulonephritis also occurred in association with other diseases such as equine infectious anemia, chronic hog cholera, canine pyometra, dirofilariasis, feline leukemia virus infection and canine systemic lupus erythematosus.

Animals↗

Transitional cell carcinoma in the domestic cat.

In 17 cases of transitional cell carcinoma in cats the most common site for primary neoplasia was the urinary bladder; metastasis was recorded in five of the cases. Nine of the cases have been reported previously; the eight additional carcinomas from the files of the New York State College of Veterinary Medicine were highly invasive and had a desmoplastic response. According to WHO guidelines they were classified as nonpapillary, infiltrating; papillary, infiltrating; and variants of transitional cell carcinoma.

Animals↗