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Biomedical subjects

R A Ward

Publications and source records attributed to R A Ward.

At least 73 records · Page 4Linked to original sources

Alterations in select immunologic parameters following total artificial heart implantation.

We examined select immunologic parameters in three recipients of a total artificial heart and correlated changes with the clinical course. Two patients remain alive and were studied for 320 and 240 days, respectively; the third died 10 days after implantation. All patients demonstrated transient complement activation immediately postoperatively, as indicated by an increase in plasma levels of C3a des Arg. In the two long-term survivors, C3a des Arg levels again increased, concomitant with intravascular hemolysis associated with high blood shear rates imposed by the drive system of the heart. All three patients had a marked lymphopenia immediately postoperatively, and the two long-term survivors demonstrated marked fluctuations in total lymphocyte count. There was a progressive decline in the number of peripheral blood helper/inducer T cells in the two long-term survivors. A large number of activated (HLA-DR positive) suppressor/cytotoxic T cells were also noted in these two patients. A progressive decrease in B cells was also observed; however, total IgG and IgM levels were not decreased. No changes in neutrophil phagocytic or respiratory burst capacities were identified. The cause of these changes in lymphocyte populations is not clear; however, they may have impact on the use of this device as a bridge to transplantation and may lead to decreased immunocompetence during long-term use.

Blood Transfusion↗

Thromboembolic and infectious complications of total artificial heart implantation.

Thromboembolic and infectious events were found to be major complications of long-term total artificial heart implantation in two patients. Similar complications have been reported in other patients, as well as in animal studies. The thromboembolic events and the infectious complications appear to be interrelated. On the one hand, thrombi located on the valves and at the vascular anastomoses of the artificial heart were found to be infected at autopsy; such infections are known to exacerbate formation of thromboemboli. On the other hand, the generation of microthrombi may have contributed to the RES blockade seen in our patients. We hypothesize that this RES blockade led to a progressive decrease in lymphoid system function and impaired the patients' capacity to clear microorganisms from the circulation. These phenomena arose, in part, from the design of the artificial heart and were exacerbated by associated therapy, such as blood transfusions. Our data suggest several measures that might be taken in order to reduce the severity of both the thrombogenic and infectious complications. Improved anticoagulation regimens, which increase the ability of the physician to maintain the proper balance between thrombotic and hemorrhagic potential, are needed. This may require not only improved methods of monitoring anticoagulation and predicting changes in the effectiveness of various agents as other events supervene, but also new anticoagulant and antithrombotic drugs, for example, low molecular weight heparins and prostacyclin derivatives. It is also clear that the design of the artificial heart should be modified in order to improve fluid dynamics so that they will approximate as closely as possible those of the natural heart. This includes redesigning the mounting of the valves to eliminate crevices and discontinuities that allow stagnant flow and predispose to thrombus formation as well as imposing a dP/dt that minimizes shear-related hemolysis, thereby minimizing the need for blood transfusions. Prevention of infections presents a more difficult problem. Transcutaneous lines (regardless of their use) are an obvious route for infection, and attention should be given to minimizing the number and length of use of monitoring lines. However, until a totally implantable drive system is available, the drive lines will remain a potential avenue for the introduction of infections. The risk may be minimized by rigorous attention to care of the exit sites and by improved designs that will provide a better mechanical barrier by, for example, enhancing epithelial ingrowth into the materials of the drive line.(ABSTRACT TRUNCATED AT 250 WORDS)

Candidiasis↗

The effects of doxapram on breathing, heart rate and blood pressure in fetal lambs.

In experiments to assess its value in the study of fetal arterial chemoreceptor reflexes, doxapram (0.5 - 2 mg i.a.) given to unanaesthetized fetal lambs in utero in low voltage electrocortical activity stimulated fetal breathing in 73% of trials. The response began within a few seconds and lasted up to 5 min. This response to doxapram was present in intact or mid-collicular brainstem transected fetuses and after bilateral section of the carotid sinus nerves and cervical vagosympathetic trunks (denervation). In intact and brainstem transected fetuses, doxapram injections were followed by a modest rise in arterial pressure and a small fall in heart rate. After denervation the rise in arterial pressure was fourfold and the heart rate increased. Electrocortical activity and limb movements were not affected in any group of lambs, and fetal breathing was not induced during isocapnic hypoxia. It is concluded that doxapram stimulates fetal breathing by a central action below the pons, and that it can therefore not be used to study peripheral arterial chemoreceptor function in utero.

Animals↗

Calcium carbonate precipitation in bicarbonate hemodialysis.

Calcium carbonate has been observed to precipitate in the fluid pathway of dialysate delivery systems dispensing bicarbonate-containing dialysates. Such precipitation can occlude the fluid pathway, leading to system malfunction and increased maintenance requirements. We show that commercial supplies of sodium bicarbonate are contaminated by trace amounts of sodium carbonate. This contamination may result in immediate precipitation of calcium carbonate on formulation of the dialysate, since bicarbonate-containing dialysates, as formulated, are metastable with respect to calcium carbonate. Sparging of the bicarbonate-containing concentrate with carbon dioxide converts any carbonate to bicarbonate, thus avoiding the formation of precipitates on addition of calcium ions.

Bicarbonates↗

Effects of apomorphine and haloperidol in fetal lambs.

Injections of 100 micrograms apomorphine (I.A.) in intact unanaesthetized fetal lambs resulted in the onset of low-voltage electrocortical activity if not already present, onset or an increase in amplitude of fetal breathing movements, and in about 50% of experiments, onset or an increase in skeletal muscle activity. These responses also occurred during isocapnic hypoxia, though the stimulation of breathing was less than in normoxic lambs. Apomorphine had no consistent effects on the blood gases, pH, heart rate or blood pressure. In fetal lambs with the carotid nerves and vago-sympathetic trunks sectioned, apomorphine had the same effects as in intact lambs, except that there was a small fall in arterial O2 pressure (Pa,O2). Haloperidol (0.5-1 mg I.V.) had no effect on spontaneous breathing movements or electrocortical activity, but blocked all responses to apomorphine for several hours. Dopamine (up to 4 mg I.V.) caused an increase in arterial pressure accompanied by bradycardia, but had no effect on breathing movements or electrocortical activity. After suprapontine brain-stem transection, the electrocortical response to apomorphine was reduced. The respiratory response was lost or reversed, with apomorphine causing a reduction in amplitude of breathing. Haloperidol reduced the incidence of breathing movements for several hours in brain-stem-transected fetuses. We conclude that there is a central pathway, including at least one dopaminergic synapse and with components above the pons, which can stimulate fetal motor activity and breathing. It does not appear to be tonically active and its normal function is unknown.

Animals↗

Effects of the alpha 2-adrenergic agonist clonidine and its antagonist idazoxan on the fetal lamb.

1. The alpha 2-adrenergic agonist clonidine was given by aortic injection to three groups of unanaesthetized fetal lambs in utero near term. One group was intact, the second had the brain stem transected just above the pons, and the third had bilateral section of the carotid sinus nerves and cervical vagi. 2. Clonidine had similar effects in all three groups. Electrocortical activity entered a high-voltage, low-frequency episode: breathing, neck and limb movements ceased; arterial pressure remained unchanged or increased; heart rate fell or remained unchanged, and the variation in both heart rate and blood pressure was much reduced. This state lasted 10-20 min, and was followed by a period of up to 4 h during which the cycling of electrocortical activity was rapid and irregular. 3. The alpha 2-adrenergic antagonist idazoxan (0.5-2.0 mg I.A.) blocked all the actions of clonidine. When given alone it usually induced a short period of low-voltage electrocortical activity and stimulated breathing movements. These effects were present in both the intact and brain-stem-transected groups, though the stimulation of breathing was significantly reduced by brain-stem transection. There were no consistent effects on heart rate or blood pressure. 4. The effects of clonidine on fetal heart rate and electrocortical activity were similar to those described in adults, but it also had inhibitory effects, not present in adults, on fetal breathing and somatic movements.

Action Potentials↗

Comparative metabolic effects of acetate and dichloroacetate infusion in the anesthetized dog.

The comparative effects of acetate (10 mmol/h/kg) and dichloroacetate (DCA) (1 mmol/h/kg and 10 mmol/h/kg) on acid-base and intermediary metabolism were assessed using the fasted anesthetized dog, undergoing controlled ventilation, as a metabolic model. Infusion of acetate resulted in a marked metabolic alkalemia and a decline in PaO2, while DCA had minimal effects on acid-base state and oxygen consumption. Serum glucose decreased with both DCA and acetate infusion, although only significantly with the latter. At infusion rates of 10 mmol/h/kg, acetate caused marked decreases, while DCA caused marked increases, in serum potassium and phosphorus. Acetate and DCA also had opposing effects on lactate and citrate levels, the former caused increases and the latter decreases in both metabolites. Pyruvate levels decreased similarly in response to both infusates. Acetoacetate and beta-hydroxybutyrate levels increased significantly with both acetate and DCA infusions; however, the increases were much greater with acetate than with DCA infusion. Blood alanine levels decreased significantly during the infusion of both acetate and DCA, whereas, free fatty acids tended to increase with acetate infusion, remained unchanged with low dose DCA and fell significantly with high dose DCA. Plasma insulin levels were sustained during acetate infusion, but fell abruptly with termination of infusion. In contrast, insulin levels fell markedly with DCA infusion and remained depressed throughout the infusion and recovery periods. Blood levels of acetate and DCA rose markedly during infusion; however, while acetate levels decreased nearly to control values during the recovery period, DCA levels remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Reactions during hemodialysis caused by allergy to ethylene oxide gas sterilization.

In patients receiving long-term hemodialysis (HD), we have examined the presence of IgE-dependent sensitization to ethylene oxide (EO) gas, which is used for sterilization of disposable medical products including dialyzers. Serum was obtained from 25 patients who experienced acute allergic reactions during HD, five patients receiving HD with isolated eosinophilia, and 37 unselected patients receiving HD. Sera from 22 of 25 of the allergic reaction group and from five of 35 of the unselected group were demonstrated to contain IgE antibodies with specificity for EO. Corresponding IgG antibodies were also present. No such antibodies were detected in serum from normal controls or ragweed-allergic patients. The serum from one patient with isolated eosinophilia had a borderline elevated IgE antibody level. These results demonstrate a close relationship between the presence of IgE antibodies to EO and HD-related allergic reactions in this patient population.

Ethylene Oxide↗

Eyewitness performance in different psychological types.

A study of 112 subjects examined the performance on a complex memory task by various Jungian psychological types. Although differences did not emerge in terms of overall accuracy, they did emerge in terms of susceptibility to postevent information. Introverts and intuitives, alone and in combination, were found to be more prone to accept both misleading and consistent postevent information, rendering them more likely to be inaccurate in the first case and more likely to be accurate in the second case. A variety of explanations are considered.

Extraversion, Psychological↗

Socialization and aging group consciousness: the effect of neighborhood age concentration.

In order to test hypotheses regarding effects of age concentration upon socialization and aging group consciousness, 1,185 persons 60 years of age and over living in areas representing low, average, and high concentrations of older persons were interviewed. Results indicated that age concentration was associated with knowledge of services and with age of persons in formal and informal neighborhood networks but was not related to attitude toward older persons in the abstract, to own age identification, to associational preference, or to taking political action. It appears that age concentration influences access to, more than choice of age peers. Both socialization and aging group consciousness are associated with age, health and socioeconomic status. It may be concluded that the ecological variable of age concentration in the range encountered by most older persons has only limited effects.

Age Factors↗

Buoyant density constancy of Schizosaccharomyces pombe cells.

Buoyant densities of cells from exponentially growing cultures of the fission yeast Schizosaccharomyces pombe 972h- with division rates from 0.14 to 0.5 per h were determined by equilibrium centrifugation in Percoll gradients. Buoyant densities were independent of growth rate, with an average value (+/- standard error) of 1.0945 (+/- 0.00037) g/ml. When cells from these cultures were separated by size, mean cell volumes were independent of buoyant density, indicating that buoyant densities also were independent of cell age during the division cycle. These results support the suggestion that most or all kinds of cells that divide by equatorial fission may have similar, evolutionarily conserved mechanisms for regulation of buoyant density.

Ascomycota↗

Subjective network assessments and subjective well-being.

Inconsistent evidence about the contributions of informal social networks to well-being may reflect a failure to measure quality as well as quantity of social involvement. The associations of both objective and subjective network characteristics with measures of subjective well-being were investigated in a sample of 1,185 persons aged 60 and over. The objective and subjective dimensions were empirically distinct, with subjective assessments of social ties and supports exhibiting stronger associations with well-being. Having enough instrumental help and contact with children appeared to be particularly important. Understanding the quality of social ties helps clarify the contributions of social involvement to the quality of life in old age.

Aged↗

Informal networks and knowledge of services for older persons.

Although informal networks may serve as lay referral to formal services, they may also reduce awareness of formal services by substituting for them. This reflects the distinction between weak and strong ties. The association between informal ties and service knowledge was investigated in a sample of 1,185 persons aged 60 and over. Such ties have generally weak associations with service awareness. Friends and neighbors appear to make small positive contributions to knowledge, as do having a confidant or instrumental helper, but ready access to children, confidants, and instrumental helpers also appears to reduce awareness of formal services. Older persons would appear to be served best by informal networks that balance weak and strong ties, yielding appropriate coordination with formal service networks.

Aged↗

Role of dialyzer contaminants in the allergic epiphenomena of hemodialysis.

Cuprophan hollow-fiber dialyzers contain contaminants including 1,2,3-propanetriol, carbohydrates, Limulus amebocyte lysate-reactive material, and particulates. In a clinical study, the role of these substances in the allergic-type response seen in some hemodialysis patients was examined. Patients were dialyzed three times per week for 6-week intervals with each of four dialyzer preparations designed to vary the burden of contaminants presented to the patient. Predialysis eosinophil counts and serum immunoglobulin (Ig) E levels were obtained weekly. White cell and platelet counts and plasma C3a and C5a levels were measured during dialysis for each dialyzer preparation. Dialyzer preparation had no effect on predialysis eosinophil counts or IgE levels. All patients demonstrated transient leukopenia and complement activation during dialysis, the magnitudes of which were unaffected by the type of dialyzer preparation. At the levels found in the dialyzers studied, it was questioned whether water-soluble extractables or particulates play any role in the allergic epiphenomena of hemodialysis.

Cellulose↗