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Biomedical subjects

R S Connell

Publications and source records attributed to R S Connell.

At least 19 recordsLinked to original sources

The effect of prolonged aspirin therapy on experimental balloon-catheter arterial wall injury.

Indications for aspirin following percutaneous transluminal angioplasty are not well defined. Although aspirin's early antithrombotic effect is believed to be beneficial, the long-term influence of aspirin on myointimal proliferative response following balloon-catheter angioplasty is still being investigated. This study quantitates arterial wall thickening, including intimal hyperplasia, at 4 months following balloon-catheter aortic injury in New Zealand white rabbits (n = 12), comparing aspirin treatment (30 mg/kg) with controls. Aspirin was administered daily for 1 month prior and 4 months following aortic injury. Myointimal proliferation was noted in both groups. The mean area of the intima and media as well as the maximum thickness of the intima were similar (p greater than .05) in both the aspirin treatment and control groups. Cellular hyperplasia was evaluated by media smooth muscle cell counts using an ocular reticle. There was a trend toward higher cell counts with aspirin treatment, although there was no significant difference between the two groups. Prolonged aspirin therapy did not alter the degree of myointimal hyperplasia at 4 months postinjury in our model.

Animals↗

Detection of human immunodeficiency virus in cell-free seminal fluid.

Human immunodeficiency virus (HIV) was detected by assay of reverse transcriptase activity in a "virus pellet" obtained by differential sucrose density centrifugation of cell-free semen from three patients with the acquired immune deficiency syndrome (AIDS), one individual with AIDS-related complex (ARC), and in an asymptomatic homosexual male. Reverse transcriptase assays indicated virus concentrations in the range of 10(8) particles/ml of semen, an accumulation substantiated by electron microscopic visualization of cell-free virus. This is the first description of cell-free retrovirus in seminal fluid and at a greater concentration than reported for blood or other body fluids or tissues. These results suggest that the male reproductive tract of humans may be a reservoir of HIV expression, and raises the possibility that the cells lining the epididymal lumen could be chronically infected with HIV. These are important considerations in formulating treatment and preventive strategies.

AIDS-Related Complex↗

Chronic hyperdynamic sepsis in the rat: I. Characterization of the animal model.

We describe a new rat model of chronic hyperdynamic sepsis. After control values for weight gain, and food and water intake of each animal were obtained over a 5-day period, male Sprague-Dawley rats weighing 370-425 g were anesthetized, catheterized to allow chronic cardiac-output measurements, and a sterile subcutaneous cavity was formed over the flank area. The animals were allowed a 3-4 day postoperative recovery period. Body weight, food and water intake, and cardiac output were measured daily. Frequent blood samples were withdrawn for bacterial cultures and white cell counts (WBC). On the third and, in some cases, the fourth postoperative day, the subcutaneous cavity was inoculated with 10(9) colony-forming units of Escherichia coli and Bacteroides fragilis. The resulting sepsis was characterized by loss of body weight in spite of normal food and water intake, increased cardiac output, increased WBC, intermittent bacteremia, decreased muscle mass, and decreased cross-sectional area of skeletal muscle myofibrils. Two levels of septic response emerged--moderate and severe. Based on the above-mentioned measurements, it was possible to categorize all long-term septic animals into these two groups. Both groups exhibited cardiac-output, body-weight, and WBC data significantly different from sham controls. Repeated inoculations of the subcutaneous abscess initiated on the third postoperative day resulted in moderate sepsis with no long-term mortality, severe sepsis with 23% mortality over a 3-week period, or a 100% mortality within 4 days, depending on the virulence of the E. coli organisms used. The new model is ideally suited for pathophysiologic studies of sustained, hyperdynamic sepsis.

Animals↗

Sperm-associated retroviruses in the mouse epididymis.

Sperm adsorbed with retrovirus particles were recovered from the epididymis of apparently normal male mice. Epididymal semen from all four mouse strains examined was positive for retrovirus (10(5) to 10(8) particles per microgram of protein) indicating that epididymal fluids and sperm may be important vehicles for murine retrovirus spread. Immunoblot analyses revealed that the banding patterns of electrophoretically separated epididymal viral proteins from the four strains of males were more similar to each other than to either xenotropic New Zealand Black virus or ecotropic Rauscher leukemia virus proteins. The results indicate that retrovirus particles, possibly a unique strain, are commonly expressed at relatively high titers in the reproductive tract of male mice and are sperm-associated.

Animals↗

Effects of E. coli endotoxin on rat plasma angiotensin converting enzyme activity in vitro and in vivo.

Angiotensin converting enzyme (ACE), a glycoprotein, is found in high concentration in pulmonary capillary endothelial cells. Several investigators have studied the relationship between various direct and indirect pulmonary insults and ACE activity and in some cases have found conflict. In an attempt to clarify this relationship we have examined the effect of endotoxin on rat plasma ACE activity in vitro and in vivo. We used the synthetic ACE substrate 3H-BPAP and the assay described by Catravas and Gillis [J Pharmacol Exp Ther 217:263-270, 1981]. In vitro, a statistically significant concentration-dependent reduction in ACE activity was demonstrated (p less than .005). In vivo an intravenous dose of endotoxin (20 mg/kg) alone resulted in no significant change in plasma ACE activity. However, the combination of intravenous endotoxin (20mg/kg) and mild hemorrhage (5-10% of blood volume) caused a statistically significant reduction in plasma ACE activity by 15 min as compared to control rats with hemorrhage only (39% vs. 66%, p less than .005). This reduction persisted at 30 and 60 min. However, by 180 min ACE activity was no longer statistically different from control values. We have demonstrated an acute reduction of plasma ACE activity in the endotoxemic rat that appears to be dependent on the amount of circulating endotoxin and the presence of mild blood loss.

Angiotensin-Converting Enzyme Inhibitors↗

Pyroclastic flow injury. Mount St. Helens, May 18, 1980.

Three patients who were on the periphery of the pyroclastic flow of the Mount St. Helens eruption on May 18, 1980 were treated for severe thermal and inhalation injuries. Although exposed in identical manner, two patients arrived with heavily colonized burn wounds and developed adult respiratory distress syndrome leading directly to their death, whereas the third patient, with a noncolonized burn wound and little evidence of adult respiratory distress syndrome, survived. Evidence of inhaled ash complicating various stages of adult respiratory distress syndrome was confirmed by energy dispersive roentgenographic analysis. In the Pacific Northwest, Alaska, and the Aleutian Islands, potential for further injuries of this type in even larger numbers exists. Should these occur, those who treat the victims should be aware of the potential for severe inhalation problems in addition to the obvious burns.

Adult↗

Prevention of aconitine-induced neurogenic pulmonary edema (NPE) with hypovolemia or methylprednisolone.

Bilateral injections of aconitine in the preoptic-anterior hypothalamic area in rats produces pulmonary edema that is mediated by neurogenic mechanisms. The aim of the present study was to determine the efficacy of hypovolemia or intravenous methylprednisolone on preventing aconitine-induced pulmonary edema. Rats made hypovolemic before or after injection of aconitine or treated with 40 mg/kg methylprednisolone had normal lung weight-to-body weight ratios (LW/BW) and normal pulmonary ultrastructure. In contrast, high LW/BW and gross ultrastructural alterations were noted in rats injected with aconitine only. These findings suggest that hypovolemia was effective in preventing aconitine-induced neurogenic pulmonary edema (NPE) because it lowered the pulmonary blood volume and that methylprednisolone provided a beneficial effect by suppressing the hemodynamic response involved in NPE or by directly stabilizing the cell membranes.

Aconitine↗

The formation and effect of stored platelet concentrate microemboli on pulmonary ultrastructure.

The formation of microaggregates of platelets and leukocytes and the infusion of these aggregated blood elements in pulmonary ultrastructure and function have been extensively studied. This study was undertaken to document the formation of platelet microaggregates during storage of platelet concentrate and to determine what effect the infusion of stored platelets has on pulmonary ultrastructure. The screen filtration pressure of platelet concentrate stored at 4 degrees C. for a period of 48 hours was measured after six, 24 and 48 hours of storage. Screen filtration pressure progressively rose from a mean of 47.20 millimeters of mercury to a mean of 237.40 millimeters of mercury at 48 hours, p less than 0.02 between six and 48 hours of storage. Specimens of the lung taken for biopsy from ten patients undergoing open heart operations were examined for ultrastructural alterations. Those specimens obtained following cardiopulmonary bypass, but prior to the infusion of platelet concentrate, showed only mild ultrastructural abnormalities. Those specimens obtained for pathologic study following the infusion of platelet concentrate exhibited extensive accumulations of platelet aggregates in the pulmonary microcirculation and widespread degenerative changes in the capillary endothelial cells, intra-alveolar septae and alveolar epithelial cells. In areas in which cellular discontinuities occurred, protein exudates, fibrin clumps and red blood cells were observed in the interstitium and in the alveolar air spaces. The storage of platelet concentrate results in the formation of aggregate material. The infusion of platelet concentrate results in the formation of aggregate material. The infusion of platelet concentrate results in the formation of ultrastructural lesions, similar to those observed in situations known to lead to pulmonary dysfunction, such as following massive transfusion, hypovolemia, sepsis and hypoxia.

Biopsy↗

Absence of particle and fiber release from commercial transfusion blood microfilters.

The objective of this study was to evaluate the level of particle or fiber shedding by the five types of commercially available transfusion microfilters (Bentley, Fenwal, Johnson & Johnson, Pall and Pioneer Filters). The study was performed in a class 100 laminar flow clean bench in order to minimize particulate contamination from extraneous sources. Particle-free phosphate buffered saline was flushed through each of 12 filters of each type. The effluent particles or fibers were collected on clean Millipore filters, and their number and size determined by light microscopy and by examination of photographs of the whole Millipore filters. In addition in the case of selected representative particles identification was sought by means of scanning electron microscopy. Small particles in the effluent media were electronically counted. The microfilters did not release significant quantities of particles of fibers greater than 10 micrometer at filtration rates of 300--600 cc/min. No release of any characteristic particles or fibers was observed for any of the filter types. The present study indicates that insignificant levels of particulate matter would be introduced into blood by any of the five types of blood microfilter.

Blood Transfusion↗

Fine structural changes in the gastro-intestinal tract of the hypoxic puppy: a study of natural history.

The present study demonstrates that a 2 hr period of sustained hypoxia results in a focally destructive process, a process which resolves by 5 days. That the changes described in earlier work are not overwhelming to the animal suggest that an early, focal, and reversible stage of the development of acute enterocolitis in the puppy can be described with the aid of electron microsocpy.

Animals↗

Microcirculatory changes in the lung of the hypoxic and hypovolemic puppy: an electron microscope study.

The effect of systemic hypoxemia and hypovolemia on pulmonary fine structure was studied and compared in 12 Labrador puppies 6 days to 3 weeks old. Central venous and arterial pressures were monitored and arterial pH, PCO2 and PO2 recorded serially. In 4 puppies lung biopsies were taken after a two hour period of breathing 7% oxygen. Four other puppies were made hypovolemic by acute hemorrhage of 50% of the calculated blood volume and lung biopsies taken after one hour. Four control puppies were maintained under anesthesia for two hours, breathing an atmosphere of 20% oxygen before lung biopsies were taken. Both hypoxemia and hypovolemia resulted in similar pulmonary ultrastructural changes. These changes which occurred more frequently in areas where the air spaces and blood vessels were expanded, were characterized by aggregation of platelets and leucocytes in the vascular space, focal endothelial cell disruption, interstitial edema and type I epithelial cell discontinuities with exudation of plasma into the alveolar air spaces.

Animals↗

Effects of infusion of cardiotomy suction blood during extracorporeal circulation for coronary artery bypass surgery.

The effects of infusion of cardiotomy suction blood during extracorporeal circulation were evaluated in 15 patients undergoing coronary artery bypass surgery without the use of a left ventricular vent. In Group I all cardiotomy suction blood was discarded. In Groups II and III cardiotomy suction blood was reinfused without and with Dacron wool filtration, respectively. Marked hematologic changes were noted in the pericardial samples which also were reflected in oxygenator samples obtained at the end of bypass. Although postoperative bleeding was significantly greater in patients from Group II as compared to Group I, no differences were seen in total intraoperative and postoperative transfusion requirements. No patient required reoperation for bleeding. Recirculation of larger volumes of cardiotomy suction blood potentially could contribute to bleeding problems in the immediate postoperative period.

Blood↗

Pulmonary fine structural changes in children with tissue hypoxia.

Six children have undergone lung biopsy for evaluation of fine structure. Four children demonstrated increased DAVO2 preoperatively and had marked ultrastructural changes in their lungs. Such changes appear to result from embolization of microthrombi or microaggregates to the lung from under-oxygenated tissue.

Adolescent↗

Microcirculatory changes in the gastrointestinal tract of the hypoxic puppy: an electron microscope study.

Hypoxia and hypovolemia result in similar ultrastructural changes. These changes are characterized by aggregation of platelets and leukocytes in the vascular space, focal endothelial cell disruption, and appearance of increased amounts of perivascular edema, and loss of ultrastructural organization of the mucosal cell. These changes appear to relate to variations in blood flow to the mucosa of different areas of the bowel and to follow the distribution observed for necrotizing enterocolitis in the human infant.

Animals↗