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Biomedical subjects

R M Lewis

Publications and source records attributed to R M Lewis.

At least 163 records · Page 9Linked to original sources

Doppler measurement of myocardial thickening with a single epicardial transducer.

To eliminate the need for intramyocardial transducers in measuring regional left ventricular (LV) function we have developed a pulsed Doppler technique utilizing a single epicardial transducer. Wall thickening is evaluated by digitally integrating the velocity of myocardial layers passing through the sample volume located at a selected depth. Thickening fraction (TF) can then be estimated by dividing the systolic excursion by the sample volume depth. The Doppler method was compared with the transit-time method in three acute dogs by placing the 4-mm-diameter epicardial Doppler transducer over a 2-mm-diameter endocardial crystal tunneled through the LV wall. With the sample volume set to 1 mm less than the minimum LV thickness, simultaneous measurements of TF by the Doppler and transit-time methods showed good agreement (r = 0.95) during control, ischemia, volume overload, shock, and anoxia. In 28 chronically instrumented piglets signals were obtained for longer periods with Doppler transducers than with transit-time segment-length crystals. We conclude that the Doppler technique provides a high-fidelity wall thickening waveform and a good estimate of TF with minimal disturbance to the ventricle and that the technique is suitable for use in both acute and chronically instrumented animals.

Animals↗

Comparison of hepatic extraction of insulin and glucagon in conscious and anesthetized dogs.

Previous studies in anesthetized dogs demonstrated that basal hepatic extraction of insulin and glucagon are approximately 50 and 10-20%, respectively. Because of the stress of anesthesia and surgery, these values may not be relevant to normal physiology. In this study, hepatic extraction of insulin and glucagon were compared in conscious and anesthetized dogs. The conscious dogs had chronically implanted catheters in the portal and hepatic vein and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. The mean basal portal vein insulin (42 +/- 10 and 44 +/- 7 microU/ml, respectively) and glucagon (247 +/- 37 and 219 +/- 20 pg/ml, respectively) concentrations were similar in conscious and anesthetized animals. The mean basal portal vein, but not hepatic artery, plasma flow was significantly increased in conscious dogs (462 +/- 62 vs. 294 +/- 35 ml/min, respectively). Despite the increased portal vein plasma flow in conscious animals, the basal hepatic extractions of insulin (42 +/- 6 vs. 39 +/- 6%, respectively) and glucagon (12 +/- 7 vs. 7 +/- 7%, respectively) were similar in both types of animals. Arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion, which increased the amount of insulin and glucagon presented to the liver in conscious and anesthetized dogs, significantly decreased the hepatic extraction of insulin. Hepatic extraction of glucagon did not change in either group of animals. In contrast, infusion of insulin (1.0 mU/kg X min) and glucagon (4 ng/kg X min) into the portal system did not alter hepatic extraction of insulin even though the amounts of insulin and glucagon presented to that organ were similar to those obtained with arginine and CCK-PZ. The basal arterial glucose level was significantly lower in the conscious dogs but the basal hepatic glucose output was similar in the two groups. The glucose response to the infusion of arginine and CCK-PZ and exogenous hormones was significantly greater in the anesthetized animals.

Anesthesia, General↗

Pitfalls in immunofluorescence testing in canine dermatology.

Indirect immunofluorescence testing for pemphigus-like antibodies was performed on 100 dogs: 50 dogs with various nonpemphigus dermatologic diseases, 25 dogs with various nondermatologic diseases, and 25 normal dogs. One dog (generalized demodicosis) was positive for pemphigus-like antibodies at a titer of 1:10. It was concluded that canine pemphigus-like antibodies are a potential source of misinterpretation and misdiagnosis in indirect immunofluorescence testing. Direct immunofluorescence testing for IgG, IgA, IgM, and C3 was performed on the footpads of 11 normal dogs. Granular deposition of IgM at the basement membrane zone was demonstrated in 5 of the 11 dogs. It was concluded that direct immunofluorescence testing of canine footpads using only polyvalent immunoglobulin antisera or anti-IgM antisera may lead to misinterpretation and misdiagnosis in up to 45% of all dogs tested.

Animals↗

Pitfalls in immunofluorescence testing in dermatology. II. Pemphigus-like antibodies in the cat, and direct immunofluorescence testing of normal dog nose and lip.

Indirect immunofluorescence testing for pemphigus-like antibodies was performed on 75 cats: 25 cats with various nonpemphigus dermatologic diseases, 25 cats with various nondermatologic diseases, and 25 normal cats. Pemphigus-like antibodies were not detected. It was concluded that neither true pemphigus antibodies, nor pemphigus-like antibodies are commonly detected by indirect immunofluorescence testing in the cat. Direct immunofluorescence testing for IgG, IgA, IgM, and C3 was performed on the nose and lip of 15 normal dogs. Granular deposition of IgM at the basement membrane zone of the nose was demonstrated in 11 of the 15 dogs. Lip was consistently negative. It was concluded that direct immunofluorescence testing of canine nose by only polyvalent immunoglobulin antisera or anti-IgM antisera may lead to misinterpretation and misdiagnosis in up to 73% of all dogs tested.

Animals↗

Observations of the immunopathology and therapy of canine pemphigus and pemphigoid.

Immunopathologic evaluation of 27 dogs with pemphigus and pemphigoid demonstrated that direct immunofluorescence testing was vastly superior to indirect immunofluorescence testing for diagnosis. Therapeutic studies in 31 dogs with pemphigus and pemphigoid demonstrated that glucocorticoids given for systemic effect were unsatisfactory as the sole form of treatment because of lack of efficacy of unacceptable side effects, or both, in over 50% of the cases.

Animals↗

Studies on the mechanism of an antibiotic ionophore, R02-2985 (X537A) in the conscious chronically instrumented dog: involvement of the prostaglandin synthetic pathway.

Conscious dogs were pretreated with a large dose of indomethacin in order to test the hypothesis that prostaglandin synthesis may be involved in the mechanism of action of the inophore R02-2985. The increase in renal blood flow and decrease in renal vascular resistance usually produced by R02-2985 were inhibited by indomethacin. In fact, the calculated renal resistance doubled. In contrast to the effects on renal circulation, indomethacin did not affect coronary blood flow increases which occur independent of contractility changes produced by this ionophore. Effects associated with facilitated release of catecholamines, ie, increases in heart rate, central aortic pressure, and dP/dt were prolonged in comparison to the control study published earlier where these parameters returned to control levels within 2.5 h, thus suggesting that prostaglandin synthesis may somehow potentiate the effects of R02-2985 on the release of catecholamines in vivo.

Animals↗

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

To determine if there are age-related changes in response to propranolol, we studied the hemodynamic effects of this beta-adrenergic-blocking agent in 19 awake chronically instrumented puppies and compared the response to that of 9 awake chronically instrumented adult dogs. Following intravenous administration of 1 mg/kg propranolol, heart rate, cardiac output, stroke volume, systemic arterial mean blood pressure and systemic vascular resistance were reduced similarly in all age groups of animals, However, puppies were more sensitive to the beta-adrenergic-blocking effect of propranolol than adult dogs when stressed with isoproterenol.

Aging↗

Vesicular exanthema of swine and San Miguel sea lion virus: experimental and field studies in otarid seals, feeding trials in swine.

The naturally occurring disease caused by San Miguel sea lion virus in fur seals was characterized by small fluid-filled vesicles 1 to 25 mm in diameter on the nonhaired portions of the flippers. Early epithelial lesions contained multifocal sites of cell lysis. The resultant microvesicles enlarged and coalesced, forming grossly visible macrovesicles. Mature vesicles progressed to involve all layers of the epithelium but did not involve the underlying dermis. Intradermal inoculation of vesicular exanthema of swine virus type A48 or San Miguel sea lion virus type 2 into otarid (fur) seal pups caused plaque-like lesions around inoculated coronary bands. These swellings regressed without rupture by 96 hours postinoculation. One seal inoculated with San Miguel sea lion virus had a linear lingual erosion at ten days postinoculation. Virus was isolated from this site and from two uninoculated sites, the tonsil and testicle. Contact controls showed no evidence of infection. Virus was isolated in low titers from some sites of inoculation and draining lymph nodes from seals infected with vesicular exanthema of swine virus. Virus was recovered more easily, in higher titers, and from more tissues, from seals infected with San Miguel sea lion virus. Inoculated seals tested after four to ten days seroconverted. Feeding swine seal tissues from the inoculation experiments resulted in seroconversion in swine which were fed tissues from seals infected with vesicular exanthema of swine virus but not in those which were fed tissues from seals infected with San Miguel sea lion virus.

Animals↗

The pathogenesis of vesicular exanthema of swine virus and San Miguel sea lion virus in swine.

Vesicular exanthema of swine virus type A48 or San Miguel sea lion virus type 2, when inoculated intradermally into swine, resulted in fluid-filled vesicles at the sites of inoculation in the snout, coronary band, and tongue. Pigs that developed vesicles also had fevers. Secondary vesicle formation varied, depending on virus serotype. Viremia was found in one pig infected with San Miguel sea lion virus five days after infection. Virus was recovered from nasal-oral passages for up to five days after infection in both groups of pigs and from the gastrointestinal and urinary tracts of pigs infected with San Miguel sea lion virus. Neutralizing antibodies began to increase three days after inoculation and reached peak titers in seven to ten days. In the absence of secondary bacterial infection, healing was well advanced by ten days after inoculation. Lesions usually were limited to nonhaired portions of the integument and tongue. Individual epithelial cells became infected when a break in the skin allowed virus access to susceptible epithelial cells from either exogenous or endogenous sources. Individual infected cells ruptured and adjacent cells were infected, resulting in the formation of multiple microvesicles. Centrifugal coalescence of microvesicles led to formation of grossly visible macrovesicles. Lesions rarely developed from viral contamination of intact hair follicles. A mild virus-induced encephalitis was seen in pigs infected with vesicular exanthema of swine virus, and virus was recovered from brain tissue of pigs infected with San Miguel sea lion virus.

Animals↗

Automatic increases in mean airway pressure during mechanical ventilation.

The response of a time-cycled, continuous-flow, pressure-limited infant ventilator to changes in lung compliance was assessed by use of a variable-compliance test lung. A 50% reduction in lung compliance produced an automatic increase in mean airway pressure (MAP). Increases in MAP averaged 17% over baseline values. Factors that favored a large increase in MAP when lung compliance was reduced were a high original lung compliance, a low ventilator compliance, a high I:E, and ventilation with a triangular inspiratory pressure wave. The increase in MAP was accompanied by a change in the inspiratory pressure wave from triangular to square. Increases in MAP were not seen when the pressure wave was initially square. Automatic increases in MAP when lung compliance decreases may help to minimize decreases in PaO2; however, pulmonary barotrauma and increases in intracranial pressure could also result. The factors that allow for automatic MAP increases may also allow for automatic decreases in MAP as lung compliance improves. The advantages and disadvantages of automatic changes in MAP merit further study.

Airway Resistance↗

Pemphigus and pemphigoid in dog and man: comparative aspects.

A review of canine pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus erythematosus, and bullous pemphigoid shows them to share many clinicopathologic similarities with their human counterparts. Because of their numerous analogies in clinical presentations, histopathologic and immunopathologic findings, and therapeutic results, canine and human pemphigus and pemphigoid may represent a valuable area for comparative dermatologic research.

Animals↗

Biochemical studies of the excitable membrane of Paramecium tetraurelia VI. Endogenous protein substrates for in vitro and in vivo phosphorylation in cilia and ciliary membranes.

The endogenous protein kinases of isolated Paramecium tetraurelia cilia phosphorylated approximately 30 ciliary polypeptides in vitro. Labeling with [gamma-32P]ATP was not proportional to the amount of each protein in cilia; some minor polypeptides (e.g., 67,000 and 180,000 mol wt) were more heavily labeled than some major polypeptides. Certain of the endogenous substrates for protein kinase were localized in the ciliary membrane (130,000, 86,000, 67,000, and 45,000 mol wt); others were found in axonemes or in both fractions. With cilia from bacterized cultures in the undefined Cerophyl medium, the labeling of specific endogenous phosphate acceptors was altered by pH, cyclic AMP, and cyclic GMP, but the labeling pattern was not affected by the presence of Na+ or K+ (15 mM), Ba++ (5 mM), Ca++ (10(-5) or 10(-4) M), or EGTA. Very similar results were obtained with cilia from cells grown axenically in a semidefined medium; the molecular weights and the extent of phosphorylation of the phosphopolypeptides were comparable to those of cilia from bacterized Cerophyl cultures, although no significant cyclic nucleotide effects were observed in the axenic cilia. Most of the phosphopolypeptides labeled in vitro also turned over rapidly in vitro. The phosphoprotein phosphatase responsible for turnover was partially inhibited by 5 mM NaF. The pattern of ciliary polypeptides labeled in vivo was similar to that observed in the in vitro experiments, although the relative intensities of labeling differed. Six behavioral mutants of Paramecium, known to have defects in the excitable membrane that regulates the ciliary beat, showed normal patterns of ciliary protein phosphorylation in vitro, with and without added cyclic nucleotides, at both pH 6.0 and pH 8.0. The mutants also had apparently normal phosphoprotein phosphatase. The Paranoiac A mutant, however, showed a reduction in cyclic GMP-stimulated protein kinase activity.

Animals↗

Myocardial protection from ischemic arrest: potassium and verapamil cardioplegia.

Prolonged normothermic myocardial ischemic arrest results in myocardial dysfunction. This study has investigated the technique of preserving myocardial function by a single bolus intracoronary infusion of combination potassium and verapamil at the onset of ischemic arrest. Sixty-one dogs underwent cardiopulmonary bypass with 60 min of ischemic arrest: 25 received no myocardial protection, 12 received a single intracoronary bolus of KCl, 12 received combination verapamil and KCl, and 12 received verapamil alone. Following the ischemic arrest, hearts protected by combination of potassium and verapamil demonstrated better survival evidenced by the ability of all 12 dogs to resume normal hemodynamic function. The hemodynamic function in the combination potassium and verapamil group also demonstrated better cardiac output, left ventricular dF/dt, and myocardial segment shortening than survivors in the other groups. Subsarcolemmal (SSL) and intermyofibrillar IMF) mitochondria were isolated from these hearts and function evaluated. NADH-linked oxygen consumption was impaired as was calcium transport in the SSL from unprotected ischemic hearts. Intermyofibrillar mitochondria were not different from control or sham. The hearts protected by verapamil and potassium demonstrated normal mitochondrial function.

Animals↗

The effect of tolbutamide and hepatic extraction of insulin and glucagon and hepatic glucose output in anesthetized dogs.

The effects of tolbutamide and insulin infusion on hepatic extraction of insulin and glucagon and on hepatic glucose output were compared in anesthetized dogs. The basal hepatic extraction of insulin was not significantly different in the two experiments (62 +/- 7% vs. 49 +/- 8%). The fraction of insulin extracted by the liver was not changed by either tolbutamide or insulin administration. In contrast, hepatic extraction of glucagon significantly increased from a basal value of 12 +/- 8% to 41 +/- 12% 30 min after tolbutamide, coincident with hypoglycemia and increased secretion of glucagon. The percent hepatic extraction of glucagon did not change during insulin infusion despite similar hypoglycemia and an even greater increase in the amount of glucagon reaching the liver. Tolbutamide and insulin produced a transient fall in hepatic glucose output which was associated with a significant increase in the insulin to glucagon molar ratio of the portal vein. Despite the persistence of hypoglycemia, hepatic glucose production returned to control values, and the portal venous insulin to glucagon molar ratio returned toward normal. Thus, the initial hypoglycemia after tolbutamide and insulin treatment reflects decreased hepatic glucose production, while the later effects represent increased peripheral glucose utilization. Hepatic glucose output correlated better with the portal venous insulin to glucagon molar ratio than the ratio of the hormones removed by the liver. These findings indicate that insulin and glucagon extraction by the liver are quite different and are independently regulated. Tolbutamide directly increases the fraction of glucagon removed by the liver. Because of changes in hepatic extraction after tolbutamide, increased pancreatic secretion of glucagon might not be reflected in its peripheral concentration.

Animals↗