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Biomedical subjects

D Davis

Publications and source records attributed to D Davis.

At least 217 records · Page 12Linked to original sources
PubMed1988

Performance of a demand oxygen saver system during rest, exercise, and sleep in hypoxemic patients.

Demand oxygen systems have been shown to be effective in treating hypoxemia during seated rest and during exercise, but the performance of these systems during sleep has not been previously studied. We compared the efficacy of a new demand oxygen saver system with that of continuous flow nasal oxygen during the usual activities of daily life including sleep, seated rest, and exercise. Six hypoxemic patients were studied. All six had chronic obstructive pulmonary disease, though one patient had kyphoscoliosis with mixed obstructive and restrictive lung disease. Patients were studied during each activity of daily life while receiving supplemental oxygen by continuous flow nasal cannula at 2 liters per minute and during use of the demand oxygen saver system. The demand oxygen system produced arterial oxygenation equivalent to continuous flow nasal cannula under all conditions while utilizing substantially less oxygen. When compared with administration of oxygen by continuous flow nasal cannula, the demand oxygen saver cannula utilized only 45 percent as much oxygen during seated rest, 44 percent as much oxygen during exercise, and 39 percent as much oxygen during sleep. Our data support the use of demand oxygen systems for treatment of hypoxemia in patients with chronic obstructive lung disease.

Aged↗
PubMed1988

The peripheral distribution of cardiac output in heart failure.

There are two sets of compensatory mechanisms activated when the heart fails: cardiac mechanisms that try to maintain a normal cardiac output and peripheral circulatory mechanisms that try to maintain blood pressure to perfuse the heart and the brain. The latter are most important during the stress of exercise. During exercise, two patterns of responses are noted: 1) blood vessels supplying active skeletal muscle fail to dilate normally, and 2) blood vessels supplying other visceral organs constrict excessively. The inability of skeletal muscle resistance vessels to dilate normally to a metabolic stimulus is related to sodium and water accumulation in the vessels and to a deconditioning response. These effects probably are at the small artery level. This results in an abnormal metabolic response to exercise. Vasoconstriction in visceral organs is related to neurogenic (sympathetic adrenergic) and humoral (angiotensin, norepinephrine, and vasopressin) mechanisms. The peripheral sympathetic nervous system is the primary determinant of the high plasma norepinephrine levels seen in heart failure. The role of the sympathetic nervous system is to provide for acute vasoconstriction and the renin-angiotensin system is to provide for chronic visceral vasoconstriction. These circulatory mechanisms operate most effectively over different time frames that are either short (sympathetic nervous system), intermediate (renin-angiotensin system), or long (deconditioning, vascular stiffness). When treatment is successful these systems return to normal over similar time frames.

Cardiac Output↗
PubMed1988

A randomized controlled trial assessing the impact of problem-based versus didactic teaching methods in CME.

A Continuing Medical Education short course was designed to examine the effect of presenting topics in three learning formats - traditional lectures, large-group, case discussions or small-group, problem-solving sessions, on knowledge and performance of family physicians. The physicians in the small group session rated the CME short course higher and performed better on one aspect of patient management than the lecture or large group physicians but there were no other differences between groups on knowledge or physician performance.

Clinical Competence↗
PubMed1988

Bronchoalveolar lavage in an animal model of acute lung injury. Relationship between enhanced membrane permeability and transvascular neutrophil flux.

Results of studies utilizing bronchoalveolar lavage (BAL) have led workers to propose that the neutrophil serves as the pivotal cellular element responsible for promoting enhanced alveolar capillary membrane (ACM) permeability in certain forms of acute lung injury. The authors performed BAL on anesthetized, intubated, instrumented sheep before and after the administration of 15 mg/kg ethchlorvynol, a known pulmonary edemagenic agent. Bronchoalveolar lavage fluid (BALF) protein content increased from 0.62 +/- 0.05 to 1.5 +/- 0.15 mg/ml, and the percentage of neutrophils recovered from 2% +/- 1% at baseline to 35% +/- 7% (P less than 0.01) 60 minutes after infusion of ethchlorvynol. After ethchlorvynol infusion into neutropenic sheep (less than 500 cells/microliter), BALF protein content increased from 0.35 +/- 0.08 to 1.5 +/- 0.69 mg/ml (P less than 0.01) with no increase in BALF neutrophil count. In 3 non-neutropenic sheep BAL was performed at 15 and 30 minutes after ethchlorvynol infusion. BALF protein content increased significantly within 15 minutes, whereas the percentage of neutrophils did not change. These findings suggest coexistent ACM injury as reflected by increases in BALF protein content and increased number of neutrophils in BALF does not necessarily imply a cause-and-effect relationship in certain forms of acute lung injury.

Acute Disease↗
PubMed1988

Experimental vaccination of rats with Dermatophilus congolensis zoospores.

The number of zoospores recoverable from the skin of rats five days after challenge with Dermatophilus congolensis, was reduced if the rats had been injected intradermally with zoospores of this bacterium two weeks previously. The difference between zoospore recovery in vaccinated and control rats was increased when the challenge was applied to scarified skin. Assays involving a 24-hour delay between scarification and challenge gave the greatest difference in zoospore recovery. In rats which had been vaccinated 12 weeks before challenge protection was reduced.

Actinomycetales Infections↗
PubMed1987

Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: effects on enzyme induction and immunotoxicity.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254 induced the cytochrome P-450 dependent monooxygenases, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) in rat hepatoma H-4-II E cells and C57BL/6J mice. It has been proposed that both Aroclor 1254 and 2,3,7,8-TCDD induce these enzymes via a common mechanism which features initial binding to the aryl hydrocarbon (Ah) cytosolic receptor protein. The major difference between these compounds was the relative potency (i.e. 2,3,7,8-TCDD much greater than Aroclor 1254). Cotreatment of rat hepatoma H-4-II E cells or C57BL/6J mice with a dose of 2,3,7,8-TCDD which submaximally induces AHH and EROD and a dose of Aroclor 1254 which exhibited little or no induction activity resulted in significant antagonism of the induction effects of 2,3,7,8-TCDD. For example, cotreatment of C57BL/6J mice with 2,3,7,8-TCDD (15 nmol/kg) and Aroclor 1254 (25, 75 and 150 mumol/kg) resulted in up to 23% antagonism of AHH induction by 2,3,7,8-TCDD. Moreover, cotreatment with a higher dose of the 2,3,7,8-TCDD agonist (30 or 50 nmol/kg) partially reversed some of the antagonism by Aroclor 1254. In vivo antagonism was observed only at Aroclor 1254/2,3,7,8-TCDD molar ratios of 1667:1, 5000:1 and 10,000:1. Administration of 2,3,7,8-TCDD (3.72 nmol/kg) to C57BL/6J mice resulted in a 76% decrease in the splenic plaque forming cell response to sheep red blood cells. This T-cell mediated immunotoxic effect of 2,3,7,8-TCDD segregates with the Ah locus. In contrast, administration of 5, 15, 75 and 150 mumol/kg of Aroclor 1254 resulted in impairment of the immune response only at the highest dose level. However, cotreatment of mice with 2,3,7,8-TCDD (3.72 nmol/kg) and Aroclor 1254 (5, 15 or 75 mumol/kg) resulted in no significant decrease in the plaque forming cell response and complete protection from the immunotoxicity of 2,3,7,8-TCDD. Cotreatment of the mice with Aroclor 1254 (75 mumol/kg) and a higher dose of the 2,3,7,8-TCDD agonist resulted in partial reversal of the protective effects of Aroclor 1254. The in vitro and in vivo data suggest that within specific antagonist/agonist dose ratios, Aroclor 1254 can antagonize at least 2 Ah receptor-mediated effects of 2,3,7,8-TCDD, namely AHH induction and immunotoxicity.

Animals↗
PubMed1987

Reaction of cytochromes c and c2 with the Rhodobacter sphaeroides reaction center involves the heme crevice domain.

In order to define the interaction domain on Rhodobacter sphaeroides cytochrome c2 for the photosynthetic reaction center, positively charged lysine amino groups on cytochrome c2 were modified to form negatively charged (carboxydinitrophenyl)- (CDNP-) lysines. The reaction mixture was separated into several different fractions by ion-exchange chromatography on (carboxymethyl)cellulose. Tryptic digests of these fractions were analyzed by reverse-phase peptide mapping to determine the lysines that had been modified. Fraction A was found to consist of a mixture of singly labeled derivatives modified at lysine-35, -88, -95, -97, and -105 and several other unidentified lysines comprising 32% of the total. Although it was not possible to resolve these derivatives, all of the identified lysines are located on the front surface of cytochrome c2 near the heme crevice. The second-order rate constant for the reaction of native cytochrome c2 with reaction centers was 2.0 X 10(8) M-1 s-1, while that for fraction A was 20-fold less, 1.0 X 10(7) M-1 s-1. This suggests that lysines surrounding the heme crevice of cytochrome c2 are involved in electrostatic interactions with carboxylate groups at the binding site of the reaction center. The reaction rates of horse heart cytochrome c derivatives modified at single lysine amino groups with trifluoroacetyl or trifluoromethylphenylcarbamoyl were also measured. Modification of lysine-8, -13, -27, -72, -79, and -87 surrounding the heme crevice significantly lowered the rate of reaction, while modification of lysines in other regions had no effect. This indicates that the reaction of horse heart cytochrome c with the reaction center also involves the heme crevice domain.

Amino Acid Sequence↗
PubMed1987

Enhanced metabolic vasodilation secondary to diuretic therapy in decompensated congestive heart failure secondary to coronary artery disease.

Since sodium and water retention have been implicated as major factors limiting maximal metabolic vasodilation in congestive heart failure (CHF), the effect of rigorous diuresis on maximal vasodilatory capacity was studied systematically in 9 subjects hospitalized with decompensated CHF. Peak reactive hyperemic blood flow, measured by strain-gauge plethysmography, was used as an index of maximal vasodilatory capacity. After 24 hours of diuresis and a 2.2-kg weight loss, maximal flow increased from 19.9 to 26.1 ml/min X 100 ml (p less than 0.05). Despite a further 1.4-kg weight loss between 24 and 48 hours, maximal blood flow increased no more (26.1 to 25.8 ml/min X 100 ml). Since blood pressure did not change significantly, minimal forearm resistance and maximal conductance showed similar improvements. It is unlikely that vasoconstrictor hormone changes could account for this effect since a marked decrease in plasma norepinephrine occurred in only 2 of 8 subjects and plasma renin activity decreased in only 1 subject. As a group there was no significant change in norepinephrine level, which remained substantially above normal (1,525 to 1,148 pg/ml), or in plasma renin activity (12.3 to 18.9 ng/ml/hour). Because the improvement in vasodilator capacity reached a plateau by 24 hours despite continued diuresis, and because peak reactive hyperemic blood flow was still 32% below normal, it is suggested that a second mechanism besides sodium and water retention is responsible for a significant portion of the impaired peripheral vasodilation in CHF.

Aged↗
PubMed1987

Liposomes as adjuvants with immunopurified tetanus toxoid: the immune response.

Immune responses of BALB/c mice to immunopurified tetanus toxoid entrapped in dehydration-rehydration vesicles composed of equimolar egg phosphatidylcholine and cholesterol were compared to those of free toxoid. Animals were injected intramuscularly with the free or liposomal toxoid and identical injections were repeated 4 weeks and, in some experiments, 24 weeks later. Analysis of IgG1, IgG2a, IgG2b, IgG3 and IgM in the sera by an enzyme-linked immunosorbent assay suggested that adjuvanticity of liposomes is reflected in most antibody subclasses and that there is no shift in subclasses compared to the response obtained with the free antigen, thus establishing liposomes as a type I adjuvant. In other, appropriately designed experiments, the relative importance of events following the first and second injections in determining the adjuvant effect of liposomes was investigated. It was found that liposome adjuvanticity is the outcome of events following primary immunization.

Adjuvants, Immunologic↗
PubMed1987

Liposomes as immunological adjuvants: antigen incorporation studies.

Tetanus toxoid was incorporated into liposomes composed of equimolar phospholipid and cholesterol. The toxoid was either passively entrapped into multilamellar vesicles prepared by the dehydration-rehydration procedure (DRV) or covalently coupled by diazotization to the surface of multilamellar vesicles (MLV) prepared by the classical procedure. Up to 82.3% of the antigen used was entrapped in neutral, negatively and positively charged DRV composed of a variety of unsaturated and saturated phospholipids and 63.1% was coupled to MLV composed of egg phosphatidylcholine. After freeze-drying of toxoid-incorporating DRV and MLV and subsequent rehydration, up to 93.5% of the antigen was recovered with liposomes and, in the case of MLV, retained its external localization. Upon freeze-drying in the presence of 0.25 M trehalose, up to 96.1% of the antigen was recovered with the DRV liposomes. In immunization studies using Balb/c mice, DRV composed of equimolar egg phosphatidylcholine and cholesterol were shown to act as immunological adjuvants to the entrapped tetanus toxoid. In addition, there was no difference in immune responses between DRV and MLV of identical composition but bearing the toxoid on their surface. Comparison of immune responses to the toxoid entrapped in DRV made of phospholipids with varying gel to liquid crystalline transition temperature (Tc) revealed a reduction in responses to very low or nil values for DRV made of distearoyl phosphatidylcholine (Tc 54 degrees C).

Adjuvants, Immunologic↗
PubMed1987

Internalization and processing of epidermal growth factor in aging human fibroblasts in culture.

Tissue culture lines established from newborn human skin were used as a model system to study the effects of the mitogenic hormone epidermal growth factor (EGF) on the aging process. These cells demonstrated a finite life span in culture which is presumed to be related to the in vivo aging process. Fibroblasts aged in vitro demonstrated a reduction in their ability to respond to the mitogenic effects of EGF as compared to these cells at an earlier population doubling level (PDL). This decreased responsiveness was not due to a decrease in the number of EGF receptors/cells, as cells at late PDL possessed either the same or more EGF receptors than cells at an earlier PDL. In Rat-1 fibroblasts, 125I-labeled EGF is internalized following binding to the surface receptor, and is transported through intracellular organelles where it undergoes a series of modifications which result in acidification of the EGF (Matrisian et al., 1984, J. Biol. Chem. 259, 3047). It is not known whether this acidic processing of EGF is necessary for mitogenic activity. EGF internalization and processing were therefore examined in aging human fibroblasts to determine if the decrease in EGF responsiveness is due to an alteration in EGF processing. Human fibroblasts internalized and processed pI 4.55 125I-labeled EGF to the more acidic pI 4.2, 4.35, and 4.0 species in a manner similar to Rat-1 fibroblasts. The nature of the processed product and the time course of processing was the same in cells at early and late passages. We therefore conclude that the decreased responsiveness of aged cells to EGF is not due to a defect in the EGF-processing mechanism.

Cell Line↗
PubMed1987

Termination of sustained tachycardia by external noninvasive pacing.

Invasive cardiac pacing has proved useful in the induction and termination of reentrant sustained tachycardias. In one of our two cases, programmed ventricular extra-stimulation was used to induce sustained ventricular tachycardia from the endocardial surface of the right ventricle. Induced ventricular tachycardia was terminated by burst ventricular pacing with an external cardiac pacemaker. In our second patient, external pacing was effective at inducing and terminating sustained supraventricular tachycardia. These patients illustrate that the principles of terminating sustained reentrant tachycardia with invasive pacing may also apply to noninvasive external pacing. The usefulness of this approach in treating reentrant tachycardias needs further evaluation.

Adult↗
PubMed1987

Difficulty in establishing diagnosis from lung biopsies and bronchial washing analysis in children with leukemia following bone marrow transplantation.

Three children developed severe respiratory distress at days +12, +11, and +11 following allogeneic bone marrow transplantation from donors. The first child was a 13-year-old Hispanic boy transplanted in relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). At day -14, a bronchial washing done for a streaky pulmonary infiltrate was negative for acid-fast bacilli. Miliary tuberculosis was discovered at postmortem examination. A second child, transplanted in remission of null-cell ALL, developed severe hypoxia and hypercarbia on day +11 but recovered fully following prolonged mechanical ventilation. An open-lung biopsy showed a pattern of nonspecific, diffuse alveolar damage compatible with respiratory distress syndrome. The third child was transplanted in remission of B-cell ALL and developed fatal fungal and cytomegalovirus pneumonia on day +12. In these latter two cases, it is likely that open-lung biopsy would have missed the diagnosis because of the uneven pulmonary involvement and multiple etiologies observed. All three children received cyclosporine, granulocyte transfusions, and multiple antimicrobials, including amphotericin B. Hyperfractioned total-body irradiation with lung shielding was used in the latter two patients.

Adolescent↗
PubMed1987

Liposomes as adjuvants with immunopurified tetanus toxoid: influence of liposomal characteristics.

The effect of various manipulations of liposomes composed of equimolar phospholipid and cholesterol on immune responses to the incorporated immunopurified tetanus toxoid was investigated in BALB/c mice. In studies designed to establish proper dosage for immunization and to reveal the roles of the liposomal phospholipid to toxoid mass ratio, gel-liquid crystalline transition temperatures (Tc) of the liposomal phospholipids and mode of antigen incorporation into liposomes on immune responses, animals were injected intramuscularly with various amounts of the toxoid, free, entrapped in multilamellar dehydration-rehydration vesicles (DRV) or covalently linked to the surface of multilamellar vesicles (MLV) prepared by the classical procedure. Two identical injections separated by 4 weeks were given and IgG1 and IgG2b antibodies specific for the toxoid assayed in sera by an enzyme-linked immunosorbent assay. Results suggest that the adjuvant effect of liposomes is improved considerably when liposomal phospholipid to toxoid mass ratios are as high as 2049:1; however, adjuvanticity is reduced to reach very low levels for much higher ratios (e.g. 90,361:1); antibody responses are similar for liposomes (phospholipid to toxoid mass ratios: 14.3-33.1) made of a variety of phospholipids with Tcs ranging from -32 degrees to 41.5 degrees but are low or non-existent when liposomes are made of distearoyl phosphatidylcholine (Tc, 54 degrees) (however, see Discussion); there are no differences in antibody responses between liposomes with entrapped and surface-linked toxoid.

Adjuvants, Immunologic↗