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Biomedical subjects

C Bloor

Publications and source records attributed to C Bloor.

At least 19 recordsLinked to original sources

Dilated cardiomyopathy in transgenic mice expressing a mutant A subunit of protein phosphatase 2A.

The protein phosphatase 2A (PP2A) holoenzyme consists of a catalytic subunit, C, and two regulatory subunits, A and B. The PP2A core enzyme is composed of subunits A and C. Both the holoenzyme and the core enzyme are similarly abundant in heart tissue. Transgenic mice were generated expressing high levels of a dominant negative mutant of the A subunit (A delta 5) in the heart, skeletal muscle, and smooth muscle that competes with the endogenous A subunit for binding the C subunit but does not bind B subunits. We found that the ratio of core enzyme to holoenzyme was increased in A delta 5-expressing hearts. Importantly, already at day 1 after birth, A delta 5-transgenic mice had an increased heart weight-to-body weight ratio that persisted throughout life. Echocardiographic analysis of A delta 5-transgenic hearts revealed increased end-diastolic and end-systolic dimensions and decreased fractional shortening. In addition, the thickness of the septum and of the left ventricular posterior wall was significantly reduced. On the basis of these findings, we consider the heart phenotype of A delta 5-transgenic mice to be a form of dilated cardiomyopathy that frequently leads to premature death.

Animals↗

Pain after small bowel meal and pneumocolon: a randomized controlled trial of carbon dioxide versus air insufflation.

AIM: To determine whether the use of CO2 rather than air insufflation results in less pain and/or distension in patients undergoing small bowel meal (SBM) and pneumocolon (PC). MATERIALS AND METHODS: One hundred patients for SBM and PC were randomized to receive either air or carbon dioxide (CO2) as the insufflating gas. Both the patient and radiologist were blinded to the gas being used. Patients were given a questionnaire to complete the following day. The degree and duration of abdominal pain and swelling were scored on a visual analogue scale from 0 to 100. RESULTS: Seventy-nine patients replied. The mean pain score was 28.1 for patients receiving air and 20.35 for those receiving CO2 (P < 0.05). The duration of pain was 9.0 h in the air group and 6.0 h in the CO2 group (P < 0.05). The mean abdominal swelling score was 27.1 for patients receiving air and 17.1 for those receiving CO2 (P < 0.05). The duration of swelling was 8.8 h in the air groups and 7.3 h in the CO2 group (P = 0.16). CONCLUSION: In patients presenting for SBM and PC, the severity and duration of abdominal pain and distension are significantly reduced by the use of CO2 rather than air.

Abdominal Pain↗

Magnetic resonance detection of acute pulmonary emboli in a canine model with pathologic correlation.

RATIONALE AND OBJECTIVES: The authors evaluated the accuracy of magnetic resonance (MR) imaging in depicting acute pulmonary emboli at the lobar, segmental, and subsegmental levels. METHODS: The authors induced 29 autologous emboli in five dogs and confirmed their location with angiography and anatomic dissection. MR images obtained with four sequences were independently evaluated by two radiologists to detect emboli in each vascular segment. Sensitivities, specificities, and accuracies were calculated at segmental and lobar levels. RESULTS: The fast short-tau inversion-recovery images provided the greatest conspicuity and highest overall accuracy (reader 1 = 74.3%, reader 2 = 80%). Accuracy of two-dimensional fast multiplanar spoiled gradient-recalled-echo images was limited by spatial resolution (reader 1 = 71.4%, reader 2 = 74.3%). The fast spin-echo T2-weighted and spin-echo T1-weighted sequences were intermediate in their depiction of acute emboli. Similar results were seen at the lobar level. CONCLUSION: MR images depict acute pulmonary embolism at the segmental and lobar levels with reasonable accuracy. Fast short-tau inversion-recovery sequences provided the greatest sensitivity and accuracy.

Acute Disease↗

Distribution of surfactant, lung compliance, and aeration of preterm rabbit lungs after surfactant therapy and conventional and high-frequency oscillatory ventilation.

Previous studies in preterm lambs have shown that exogenous surfactant is more uniformly distributed if given at birth before ventilation or if followed by high-frequency ventilation (HFV) after establishing conventional ventilation (CV). We hypothesized that the pre-term rabbit pup would respond similarly and that improved respiratory system compliance (Crs) would accompany improved surfactant distribution. We randomized pups (27 d gestation) into three groups: control, surfactant at birth, and surfactant after 15 min of CV (rescue). We administered dipalmitoylphosphatidyl-[3H]choline-labeled natural surfactant by tracheostomy to each of the treated groups. The two treatment groups were treated for 15 min with either HFV or CV and subsequently with CV. We measured Crs at 15, 25, 35, and 45 min after surfactant. Lungs from pups treated with CV or HFV (n = 89) for 15 min, with and without 30 min of subsequent CV, were cut into 32 pieces that were counted for distribution of label or were sectioned for quantitative morphometry (n = 36). Pups receiving surfactant after 15 min of CV had higher Crs 15 min after surfactant than either pups treated with surfactant at birth or controls (p less than 0.001). The Crs of pups 15 min after rescue surfactant followed by HFV was lower than that of pups treated with CV (p less than 0.05) but was higher than that of either control or pups treated at birth groups (p less than 0.05). Crs at 35 and 45 min after surfactant were the same in all treatment groups. Application of HFV appeared to delay the delivery of surfactant to the distal airspaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Familial aortic dissecting aneurysm.

A family is described in which nine members over two generations had an aortic dissecting aneurysm or aortic or arterial dilation at a young age. The family has been followed up since 1977 after the death of a second teenager from a kindred of 11. None of the patients had the Marfan syndrome or a history of systemic hypertension. Three members died of ruptured aortic dissecting aneurysm and acute hemopericardium at 14, 18 and 24 years of age, respectively; a fourth member died suddenly at age 48 years, a few years after aortic repair for aneurysmal dilation. One member underwent surgical repair of an ascending aortic dissecting aneurysm at age 18 years and is still alive. Four members are currently under close medical observation for aortic or arterial dilation. Histologic examination of the aortic wall at autopsy or surgery in three patients revealed a loss of elastic fibers, deposition of mucopolysaccharide-like material in the media and cystic medial changes. Types I and III collagen from cultured fibroblasts appeared normal on gel electrophoresis. Results of indirect immunofluorescent studies of the elastin-associated microfibrillar fiber array in skin and fibroblast culture from multiple family members were also normal. This dramatic familial cluster of aortic dissecting aneurysm and aortic or arterial dilation suggests a genetically determined disease of autosomal dominant inheritance although the basic defect remains unknown.

Adolescent↗

Detection of ischemic wall dysfunction: comparison between M-mode echocardiography and sonomicrometry.

The quantification of regional ventricular function by M-mode echocardiography was compared to that by sonomicrometry in 10 closed-chest, sedated swine during temporary occlusions of the left circumflex coronary artery. Wall thickening during systole (%WT) was calculated to quantitate regional myocardial function, and percentage of fractional shortening (%FS) was calculated from both sonomicrometer tracings and M-mode echocardiograms. Ventricular dimensions at end diastole and end systole were also compared before and after 2 minutes of coronary artery occlusion. Both techniques detected significant changes in wall thickness, %WT, and %FS after occlusion. Changes in %WT during coronary artery occlusion detected by M-mode echocardiography and sonomicrometry had a significant linear relationship (p less than 0.05). Discrepancy between the two techniques in the measurement of wall thickness at end diastole was attributed to the difficulty in measuring relatively small distances with M-mode echocardiograms. However, we conclude that the clinical M-mode echocardiogram is capable of detecting acute regional wall dysfunction associated with ischemia.

Animals↗

The physiologic effects of oxygen transport by hemoglobin solutions.

Two chronic animal models and one acute animal model were used to evaluate exchange transfusion with stroma-free hemoglobin solutions. A direct comparison was made between stroma-free hemoglobin solutions having differing oxygen offloading characteristics as well as a colloid solution consisting of 7% bovine albumin. These studies involved a partial exchange involving approximately 50% of the animal's blood volume to simulate a clinically more appropriate partial blood replacement situation. We noted a consistent increase in the arterial oxygen content of animals exchanged with the stroma-free hemoglobin solutions and some modest improvement in oxygen dynamics. Our studies examining myocardial contractility, especially those carried out in the right heart bypass swine preparation failed to substantiate any difference between an exchange with albumin or stroma-free hemoglobin solutions. The conscious animal models examined both at rest and at exercise demonstrated marked differences in exercise response. Animals exchanged transfused with stroma-free hemoglobin solutions often had an almost normal exercise response while those animals exchanged with non-oxygen carrying albumin solution frequently failed to exercise on a treadmill. Blood flow measurements using radiolabeled microspheres were performed in chronically instrumented swine. These animals had a normal variation in organ blood flow during exercise which was noted both during the control period as well as following exchange with stroma-free hemoglobin solutions. Animals exchanged transfused with albumin had a marked derangement in organ blood flow apparently reflecting the decreased oxygen availability. Results from these three studies substantiate a significant benefit to animals undergoing a 50% exchange when that exchange is done with an oxygen carrying solution such as stroma-free hemoglobin solutions as opposed to a non-oxygen carrying but oncotically active solution such as albumin solution. These studies seem to offer encouragement to the continued investigation and ultimate clinical utilization of hemoglobin solutions as an appropriate blood substitute.

Animals↗

Effects of experimental volume-overload hypertrophy on myocardial blood flow and cardiac function.

To examine the effects of volume-overload hypertrophy on regional myocardial perfusion, we determined myocardial blood flows with microspheres at rest, during exercise, and during exercise with adenosine infusion in dogs with aortocaval fistulas for 12 wk (group 2) and sham-operated controls (group 1). A subgroup of six animals (group 3) was studied both before and after shunt closure in order to separate the influences of hypertrophy from the hemodynamic effects of the fistula. Epicardial blood flows in animals with patent fistulas were significantly greater than in controls under all conditions (P less than 0.05). However, endocardial blood flows were lower at maximal exercise and with adenosine, so that the endocardial-to-epicardial blood flow ratios were reduced 36 and 28%, respectively(P less than 0.05). These flow abnormalities were reversed by closing the fistula prior to regression of hypertrophy. Moreover, coronary resistance per unit of myocardium was not different for the three groups. These results suggest that the blood-flow abnormalities seen in the exercising dog with an aortocaval fistula are secondary to hemodynamic considerations and not to hypertrophy itself. Low aortic diastolic pressures and high myocardial oxygen demands during exercise may combine to produce subendocardial hypoperfusion in this model.

Animals↗

Serum enzyme abnormalities in swine associated with systemic infection and fever.

Yucatán miniswine with systemic infections (C. pyogenes and S. marcescens) and accompanying elevated body temperature, also have increased serum creatine kinase (CK), lactate dehydrogenase (LD) and gamma-globulin (GG) levels. The CK and LD levels increase with fever due to infection and decrease as antibiotics are administered and the body temperature is lowered. The GG levels remain elevated. Body temperature due to infection should be taken into account when utilizing CK and LD to assess skeletal muscle, cerebrovascular and myocardial damage.

Animals↗

Heterogeneous response patterns of aortae to norepinephrine.

Concentration-contractile response curves for the thoracic (TA) and abdominal (AbA) aortae from spontaneously hypertensive (SHR) and normotensive control (WKY) rats were determined using adrenergic agonists. The concentrations of epinephrine (E) and norepinephrine (NE) necessary to produce a maximum response in the WKY TA were 7.07 x 10(-7) M and 1.68 x 10(-6) M, respectively. At greater concentrations TA responded with progressive relaxation. When similarly tested, SHR TA responded with significantly less relaxation. The concentrations of E and NE necessary to produce a maximum response in the WKY AbA were greater than 1.0 x 10(-5) M. No significant relaxation occurred at greater concentrations. The relaxation responses of the SHR AbA were no different than their normotensive controls. When propranolol was used the results suggested that relaxation is mediated by the beta-adrenoreceptor. The use of the beta 2-agonist, salbutamol, confirms the hypothesis that relaxation occurring in response to high concentrations of NE and E is partly a beta 2-adrenoeceptor phenomenon, and that this beta 2-adrenergic response decreases with early hypertension in TA. The different response patterns produced may partially account for the diversity of results regarding vascular sensitivity to vasoactive agents in the literature.

Albuterol↗

Comparative pathology of silicate pneumoconiosis.

A simple pneumoconiosis with lamellar birefringent crystals was observed in animals dying in the San Diego Zoo. We studied 100 autopsies from 11 mammalian and eight avian species. In mammals, mild pulmonary lesions comprised crystal-laden macrophages in alveoli and lymphatics. Interstitial fibrosis was present in 20% of cases. There were no nodules. In birds, dust retention produced large granulomas around tertiary bronchi without fibrosis. Mineralogic analysis using scanning and transmission electron microscopy showed most of the crystals to be silicates. Ninety percent were complex silicates, with aluminum-potassium silicates comprising 70% of the analyzed particles. Electron and x-ray diffraction showed the silicates to be muscovite mica and its hydrothermal degradation product, ie, illite clay. This mica was also present on filtration membranes of atmospheric air samples obtained from the San Diego Zoo. The amount of dust retention was related to the animal's age, anatomic or ecologic variances, and length of stay in the San Diego Zoo. Its semidesert atmosphere is rich in silicates, which are inhaled and deposited in the lungs. Similar mica-induced lesions are found in humans living in this region or the Southwest of the USA. This simple pneumoconiosis is likely to be widespread in human populations living in desert or semidesert climates.

Animals↗