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Biomedical subjects

D A Cox

Publications and source records attributed to D A Cox.

At least 73 records · Page 4Linked to original sources
PubMed1989

Control of shear stress in the epicardial coronary arteries of humans: impairment by atherosclerosis.

Altered arterial wall shear stress may adversely affect vascular endothelium and contribute to atherogenesis. This study examined the hypothesis that, in humans, dilation of normal coronary arteries with increased flow limits increases in shear stress and that loss of flow-mediated dilation in atherosclerosis results in failure to control shear stress. Coronary blood flow was increased by infusing adenosine (0.022 to 2.2 mg/min) through a 2.5F Doppler flow catheter positioned in the middle segment of the left anterior descending coronary artery in 8 patients with mild atherosclerosis but no flow-limiting stenosis and in 10 patients with entirely smooth coronary arteries. Quantitative angiography and coronary flow velocity were used to estimate shear stress in a proximal segment of the left anterior descending artery exposed to increased flow, but not to adenosine. The peak increase in blood flow was the same in smooth (371 +/- 65%) and irregular (377 +/- 50%) arteries. However, at peak flow, dilation was greater in smooth segments (16.3 +/- 2.7%) than in irregular segments (2.0 +/- 1.5%) (p less than 0.001). In each patient, smooth segments dilated with increasing shear stress (slope 7.4 +/- 0.9%), whereas irregular segments dilated less (slope 0.9 +/- 0.6%) and showed greater increases in shear stress (p less than 0.01). The peak increase in shear stress was less in smooth (189 +/- 23%) than in irregular (365 +/- 52%) segments (p less than 0.01). These results suggest a control mechanism in normal coronary arteries whereby increases in shear stress stimulate vasodilation and thus limit further increases in this force at the endothelial surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1989

Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans.

Studies in animals have suggested that increases in blood flow result in dilation of large arteries by an endothelium-dependent mechanism. Atherosclerosis can impair endothelium-dependent vasodilation to vasoactive agents. The purpose of this study was to determine whether or not large coronary arteries in humans exhibit dilation with increases in blood flow and to test the hypothesis that this response is impaired in the presence of atherosclerosis. Graded concentrations of adenosine were infused into the distal left anterior descending (LAD) coronary artery to test the dilator response of the proximal LAD to increases in blood flow. The proximal LAD was thereby exposed to changes in blood flow, but not directly to adenosine. Ten patients with angiographically smooth proximal LAD segments (group 1) and seven patients with irregularities in the proximal LAD consistent with mild atherosclerosis (group 2) were studied. Infusions of adenosine throughout the range of 0.022 to 2.2 mg/min into the LAD produced a dose-dependent increase in estimated coronary blood flow and a mean increase of 305 +/- 27% at 2.2 mg/min adenosine. At 2.2 mg/min adenosine, a striking difference (p less than 0.001) occurred between the significant flow-mediated dilation of the proximal LAD observed in group 1 (+13.2 +/- 1.3% from 2.63 +/- 0.16 mm, p less than 0.001), and the lack of dilation in group 2 (+1.8 +/- 1.5% from 3.20 +/- 0.17 mm, p = NS), despite a greater increase in coronary blood flow in group 2 (+387 +/- 29%) than in group 1 (+230 +/- 36%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1989

Reflex increase in blood pressure during the intracoronary administration of adenosine in man.

Infusion of adenosine (0.022-2.2 mg/min) into the left anterior descending (LAD) coronary artery of 26 patients produced a dose-dependent increase in blood pressure without a change in heart rate. At adenosine 2.2 mg/min, systolic pressure rose by 21.0 +/- 2.2 mmHg from 134 +/- 4.3 mmHg (P less than 0.001) and diastolic pressure increased by 10.4 +/- 1.1 mmHg from 76 +/- 1.9 mmHg (P less than 0.001). The rise in arterial pressure was associated with a 22 +/- 3.4% increase in systemic vascular resistance (P less than 0.01) and no change in cardiac output (-2.8 +/- 4.3%, P = NS). Plasma norepinephrine levels rose by 40 +/- 14% from 105 +/- 9 pg/ml (P less than 0.05) and epinephrine levels by 119 +/- 31% from 37 +/- 9 pg/ml (P less than 0.01). Right atrial infusion of adenosine produced insignificant hemodynamic effects, suggesting that systemic spillover of adenosine was not responsible for the observed effects. In 20 cardiac transplant patients with denervated hearts, LAD infusion of adenosine (2.2 mg/min) produced no change in systolic pressure (-0.1 +/- 1.6 mmHg from 139 +/- 3.4 mmHg, P = NS) and a decrement in diastolic pressure (-4.7 +/- 1.2 mmHg from 98 +/- 2.5 mmHg, P less than 0.01). Thus, infusion of adenosine into the LAD coronary artery causes a reflex increase in arterial pressure due to a rise in systemic vascular resistance, probably as a result of increased sympathetic discharge. This reflex pathway may be of importance in disease states such as myocardial ischemia, in which myocardial adenosine levels are elevated.

Adenosine↗
PubMed1989

Activation of normal murine B cells by Echinococcus granulosus.

Echinococcus granulosus protoscolex (PSC) infection of BALB/c mice led, after 4 days, to raised numbers of cells forming plaques with trinitrophenyl-treated sheep red cells and bromelain-treated mouse red cells. The findings were similar in athymic and euthymic CBA mice. Activation of B cells was accompanied by secretion of immunoglobulin, as indicated by the reverse plaque technique. In addition, co-culture of PSC with the 7OZ/3 pre-B-cell led to the induction of differentiation, resulting in the expression of surface immunoglobulin (Ig). It is concluded that E. granulosus is a polyclonal activator of B cells inducing both transformation and differentiation, and that the effect is thymus-independent.

Animals↗
PubMed1987

Serum lipid changes in a one-year, multicenter, double-blind comparison of doxazosin and atenolol for mild to moderate essential hypertension.

Proatherogenic changes in serum lipid concentrations have been implicated as one of the major risk factors in the development of coronary artery disease. In a double-blind study, the new alpha 1-adrenoceptor inhibitor, doxazosin, was compared with atenolol for effects on the serum lipid profile. Ninety-six hypertensive patients were treated for up to 1 year with either doxazosin or atenolol once daily. There were statistically significant differences (p less than or equal to 0.01) between doxazosin and atenolol after 20 to 52 weeks of treatment in changes from baseline total triglyceride levels, high density lipoprotein (HDL) cholesterol levels and HDL/total cholesterol ratio. The percentage of change from baseline and the statistical significance of the difference between treatment groups were: total triglycerides, doxazosin -5.9%, atenolol +32.4% (p = 0.01); HDL cholesterol, doxazosin +7.2%, atenolol -5.6% (p = 0.007) and HDL/total cholesterol ratio: doxazosin +8.7%, atenolol -6.2% (p = 0.006). All mean changes were in favor of doxazosin therapy. In addition, doxazosin treatment beneficially decreased total serum cholesterol levels (-1.6%) compared with atenolol (+0.6%), although not to a significant degree. The differences were maintained in the cohort of 67 patients treated for a full year. The favorable change exerted by doxazosin on the lipid profile suggests that it may have a beneficial influence on the lipid risk factor. These results, together with the sustained decrease in blood pressure achieved for up to 1 year of therapy, suggest that doxazosin may reduce the risk of coronary artery disease in susceptible patients.

Adrenergic alpha-Antagonists↗
PubMed1987

Prognostic implications of an early peak in plasma MB creatine kinase in patients with acute myocardial infarction.

To determine the prognostic implications of an early peak in plasma MB creatine kinase (MB CK) in patients with acute myocardial infarction who were not treated with an acute intervention, 342 patients with myocardial infarction confirmed by MB CK were retrospectively studied. The patients were classified into those with an early peak MB CK (less than or equal to 15 hours after the onset of symptoms, n = 84) and those with a late peak MB CK (greater than 15 hours after the onset of symptoms, n = 258). Patients with an early peak MB CK were slightly older, were more frequently female and had a higher incidence of prior myocardial infarction, congestive heart failure and arrhythmias compared with patients with a late peak MB CK. Patients with an early peak MB CK more frequently presented with ST segment depression (23 versus 11%, p less than 0.01), with anterior location of ischemia or infarction (71 versus 52%, p less than 0.01) and with a lower mean left ventricular ejection fraction (41.4 versus 47.4%, p less than 0.01). Despite more extensive left ventricular dysfunction at initial presentation, patients with an early peak MB CK had a smaller mean MB CK infarct size index (12.6 versus 18.9 g-Eq/m2, p less than 0.01), with no difference in the incidence of in-hospital complications, including death. The early left ventricular dysfunction improved in the patients with an early peak MB CK, evidenced by a 4.5% increase in ejection fraction from admission to 10 days after infarction, whereas the ejection fraction did not improve in patients with a late peak MB CK. However, the patients with an early peaking MB CK had myocardium in jeopardy as reflected by a higher incidence of ST segment depression and a decrement in the global left ventricular ejection fraction with exercise. The 4 year life table estimate for the rate of recurrent myocardial infarction after hospital discharge was higher in patients with an early peak MB CK (33 versus 22%, p less than 0.05), with an even more striking difference in the 4 year estimate for the rate of fatal recurrent infarction (20 versus 8%, p less than 0.001). The 4 year mortality estimate was markedly higher in hospital survivors with an early peak MB CK than in those with a late peak (47 versus 19%, p less than 0.0001) and, even after adjustment for differences in baseline characteristics, the residual excess mortality in those with an early peak was still significant (p less than 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1986

Echinococcus granulosus: changes in the transformational behaviour of murine lymph node cells during early infection.

Subcutaneous inoculation of living Echinococcus granulosus protoscolices (PSC) caused blastic transformation in local lymph node cells (LNC). The effect was maximal seven days post-infection (p.i.), had declined by day 21, and was prevented by killing the PSC prior to inoculation. LNC from inoculated mice also showed marked enhancement of blastogenesis in response to a secondary stimulation by live PSC in vitro. This secondary reaction occurred after exposure to living or killed PSC. There was generally enhanced reactivity to T- and B-cell mitogens at day 7. Phytohaemagglutinin was exceptional in that the killed parasite caused early changes in reactivity as above, but the live parasite induced a rise at 56 days p.i. It is concluded that E. granulosus may cause a determinate change in T-cell function.

Animals↗
PubMed1986

The antihypertensive effects of doxazosin: a clinical overview.

Doxazosin is a long-acting selective alpha 1-adrenoceptor antagonist which has been shown to be effective and well tolerated in the treatment of hypertension given in once-daily doses as monotherapy for up to 1 year or as an adjunct to thiazide or beta-adrenoceptor blockers. Doxazosin has a pharmacokinetic profile in both young adult and elderly subjects which is compatible with once-daily administration. This has been confirmed by measurement of steady state pharmacokinetics in patients receiving long-term doxazosin therapy. In controlled double-blind studies involving approximately 550 patients on doxazosin 1-16 mg once daily, significant reductions in both standing and supine BP were maintained throughout the 24 h dosing interval. Effectiveness of doxazosin in terms of BP lowering and proportion of responders was similar to that achieved with hydrochlorothiazide 25-100 mg once daily, atenolol 50-100 mg once daily, nadolol 40-160 mg once daily, metoprolol 100-200 mg per day given twice daily, or prazosin 1-20 mg per day given twice daily. Doxazosin was as effective in elderly patients as in the younger age group and was as effective in blacks as in caucasians. Doxazosin was well tolerated. Side-effects were generally mild to moderate in severity. Overall incidence, including postural effects early in treatment, was similar to that seen with the comparative agents. In comparison with placebo, doxazosin favourably increased (P less than 0.05) the HDL/total cholesterol ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Transformation induced by Echinococcus granulosus protoscoleces in unprimed murine spleen cells: identity and MHC restriction of participating cell types.

Transformation induced by Echinococcus granulosus in unprimed murine spleen cells in vitro was not prevented by rigorous T- or B-cell depletion. When naïve T- or B-cell populations were further depleted of macrophages, B-cell transformation was relatively unaffected whereas T-cell transformation was totally inhibited. Peritoneal macrophages from infected mice could present a mitogenic stimulus to purified, naïve T-cells, provided that the T-cells had identity in the I region of the H2 complex. K/D identity was neither necessary nor sufficient. It is concluded that transformation can be induced by E. granulosus in both T- and B-cells and that, at least in naïve T-cells, the stimulus can be an I region-restricted, macrophage-presented signal.

Animals↗
PubMed1985

The immune response to Echinococcus granulosus: sequential histological observations of lymphoreticular and connective tissues during early murine infection.

This paper describes the organ weight changes and the early (0 to 56 days) histological and ultrastructural changes in the lymphoid structures and injection sites after subcutaneous infection of Balb/c mice with Echinococcus granulosus protoscolices (psc). Local lymph nodes enlarged markedly, reaching maximal weight 5 to 14 days after infection (pi). Expansion of the thymus-dependent areas of draining lymph nodes was first recognized at 3 days pi and reached a maximum between 14 and 21 days pi. Lymphoproliferation within B-cell-dependent areas was less extensive and of shorter duration. Comparable, but diminished, changes were seen in contralateral lymph nodes and spleen. Lymphoid cell depletion was observed in T-dependent areas of lymphoid organs by 56 days pi. Local inflammatory reactions to psc, at the site of injection, were intense, involving neutrophils, eosinophils, macrophages and mast cells. Viable psc were present until at least 6 weeks pi. The central role of the T-lymphocyte in recognition of, and response, to E. granulosus psc is discussed.

Animals↗
PubMed1983

Pharmacokinetics of sulbactam and ampicillin following oral administration of sultamicillin with probenecid.

Eight volunteers each received lg of probenecid followed immediately by 1.5 g sultamicillin, both given by the oral route. Plasma concentrations of ampicillin and sulbactam were measured using a differential bioassay method. An ampicillin mean peak plasma concentration of 23.1 mg/l was found typically 1.5 h after dosing; the mean peak plasma concentration of sulbactam (10.0 mg/l) occurred at the same time. The mean plasma half-life of ampicillin was 1.45 h and that of sulbactam 1.3 h. The mean urinary recovery of ampicillin was 65% and that of sulbactam 62%. Five of the volunteers reported minor changes in bowel habits.

Administration, Oral↗
PubMed1983

Pharmacokinetics and bioavailability of sultamicillin estimated by high performance liquid chromatography.

Sultamicillin is an orally absorbed double ester of sulbactam (penicillanic acid sulphone, a semisynthetic inhibitor of the beta-lactamases of many Gram-positive and Gram-negative species) and ampicillin. First-pass hydrolysis of this prodrug liberates equimolar proportions of sulbactam in plasma, saliva and urine is described and was used to determine the absolute bioavailability of sulbactam and ampicillin from sultamicillin in six normal male volunteers who each received a single 750 mg oral dose of sultamicillin or an iv dose of the equivalent amounts of ampicillin (441 mg) and sulbactam (294 mg). Treatments were given in random order with not less than four days intervening. The mean peak plasma concentrations and time to peak of sulbactam and ampicillin following the 750 mg oral half lives, systemic and renal clearances for sulbactam and ampicillin were similar. The bioavailability for both drugs from sultamicillin as estimated from both plasma and urine pharmacokinetics was better than 80%. We conclude that sultamicillin is an extremely efficient prodrug for ampicillin and sulbactam and that the HPLC assay method is accurate, rapid and easier to perform than the differential microbiological assay.

Adult↗
PubMed1983

Decreased brain ascorbate levels in copper-deficient mice and in brindled mice.

Mutant brindled mice, which exhibit signs of copper deficiency, were compared to their normal brothers as well as to age-matched suckling mice that were copper-deficient (-Cu) because their dams were consuming a copper-deficient diet, and a fourth group of copper-supplemented (+Cu) suckling mice, which served as dietary controls. Copper deficiency, genetic and dietary, resulted in mice with smaller brains (87 and 75%) and lower levels of the serum cuproprotein ceruloplasmin (10 and 6.1%) when compared to their respective controls. Brain ascorbic acid concentrations were determined in these mice by high performance liquid chromatography with electrochemical detection, and levels in brindled mice and -Cu mice were significantly lower (81 and 80%) than those measured in their respective controls. Injection of cupric chloride into -Cu pups raised brain ascorbate to levels found in +Cu mice and returned catecholamine levels to normal by raising norepinephrine from a major deficit (91%) and decreasing dopamine from an excess (22%). In another study, dietary copper deficiency was produced beginning at birth and continued for 7 weeks. These older -Cu mice had minor reductions in brain ascorbate (10%) and more severe reductions in norepinephrine levels (43%). Older +Cu mice had lower ascorbate and higher norepinephrine levels compared to suckling control mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Effects of acetylcholine on large and small coronary arteries in conscious dogs.

The effects of acetylcholine, 10 microgram/kg i.v., were examined in nine conscious dogs on measurements of left ventricular pressure, dP/dt, aortic pressure, heart rate, coronary blood flow, left circumflex external coronary arterial diameter, arterial and coronary sinus O2 content and calculations of late diastolic coronary resistance and left circumflex internal coronary cross-sectional area. In conscious dogs in the absence of autonomic blockade, acetylcholine induced a rapid, transient response characterized by hypotension and peak increases in coronary blood flow (+135 +/- 14%) and coronary sinus O2 content (+5.0 +/- 0.5 volume percent) and decreases in late diastolic coronary resistance (-65 +/- 3%). The peak large coronary arterial effects were observed 60 sec later at a time when arterial pressure, left ventricular end-diastolic pressure, left ventricular dP/dt and heart rate were not significantly different from control. At this time, large coronary cross-sectional area was increased by 36 +/- 4%, whereas late diastolic coronary resistance was not significantly different from control. Beta adrenergic or combined alpha and beta adrenergic receptor blockade did not alter the responses significantly. However, the effects were abolished by muscarinic blockade with atropine methylbromide, 0.1 mg/kg. Thus, acetylcholine dilates large coronary arteries as well as coronary resistance vessels. These effects are independent of metabolic and adrenergic mechanisms, and are mediated by muscarinic receptors, inasmuch as the effects are abolished by prior muscarinic receptor blockade.

Acetylcholine↗
PubMed1982

Myocardial function in areas of heterogeneous perfusion after coronary artery occlusion in conscious dogs.

Regional myocardial function and blood flow in endocardial layers were correlated in myocardial segments subtending severely ischemic and adjacent, normally perfused myocardium in conscious dogs 1--3 weeks after recovery from coronary artery occlusion. With coronary artery occlusion induced by a hydraulic occluder, endocardial blood flow (measured with radioactive microspheres) and function (determined with an ultrasonic dimension gauge) in homogeneously nonischemic segments increased slightly but not significantly. In homogeneously ischemic segments, blood flow and function decreased (p less than 0.01) by 96 +/- 1% and 98 +/- 4%, respectively. In segments subtending zones of unequal perfusion, endocardial blood flow increased nonsignificantly in the myocardium surrounding the nonischemic crystal, while decreasing by 93 +/- 2% (p less than 0.01) in myocardium surrounding the ischemic crystal. Surprisingly, these segments behaved like homogeneously ischemic segments, i.e., endocardial shortening decreased by 92 +/- 6% (p less than 0.01). Thus, the failure to detect shortening despite normal perfusion of the myocardium surrounding one of the transducers suggest a potential problem with interpretation of regional function measurements or an inability of the apparently nonischemic myocardium to contract.

Acute Disease↗