Biomedical subjects

M E Cook

Publications and source records attributed to M E Cook.

At least 73 records · Page 4Linked to original sources

PubMed1990

Immune response of mallard ducks treated with immunosuppressive agents: antibody response to erythrocytes and in vivo response to phytohemagglutinin-P.

The ability of two in vivo tests to assay immune competence of mallard ducks (Anas platyrhynchos) treated with various immunomodulatory agents was examined. Skin responses to phytohemagglutinin-P (PHA-P) injected intradermally and serum antibody levels produced in response to sheep red blood cells (SRBC) were measured. As measured by the skin response to PHA-P, ducks injected intramuscularly with cyclophosphamide or cyclosporine did not respond differently from control-injected ducks. Dexamethasone injected intramuscularly significantly suppressed the skin response to PHA-P. As measured by antibody levels in response to SRBC, ducks injected intramuscularly with cyclophosphamide responded with antibody titers similar to controls. Cyclosporine injected intramuscularly reduced the level of immunoglobulin (Ig) G significantly in one of two experiments. Dexamethasone injected intramuscularly reduced peak total and IgG titers. These experiments provide information on the viability of these two in vivo tests to reflect immune competence of mallard ducks.

Animals↗

PubMed1990

Spontaneous high density lipoprotein deficiency syndrome associated with a Z-linked mutation in chickens.

A mutant strain of chicken previously identified by a "recessive white skin" phenotype was found to have a profound deficiency in high density lipoprotein (HDL) and apolipoprotein A-I (apoA-I). ApoA-I levels in the mutant chickens were reduced by greater than 90%. Since HDL is the predominant cholesterol transporter in chickens, the HDL deficiency was associated with a greater than 80% decrease in total plasma cholesterol. The mutation segregates with markers linked to the Z-chromosome. The structure of the apoA-I produced by the mutant chickens appeared normal as judged by two-dimensional gel electrophoresis. The genetic and biochemical evidence, therefore, suggests that the mutation is not in the apoA-I structural gene. Turnover studies were performed on labeled HDL or on labeled apoA-I preincubated with HDL prior to intravenous injection. Both types of experiments showed that both defective apoA-I production and hypercatabolism contributed to the HDL deficiency, although defective production made a much larger contribution.

Animals↗

PubMed1989

Intravenous nicardipine in severe systemic hypertension.

Sixty-six patients with severe hypertension were treated with intravenous nicardipine in 3 separate protocols. Each protocol had a common end point: Diastolic blood pressure would either reduce 25 mm Hg or measure below 95 mm Hg. Each of the 66 patients studied attained the desired clinical response end point. Intravenous nicardipine produced a gradual reduction in blood pressure, was effective in maintaining blood pressure control during constant infusion and had few undesirable effects. These observations suggest that intravenous nicardipine maybe a useful addition to a limited number of therapeutic agents currently available to the physician for treatment of hypertensive urgencies.

Adult↗

PubMed1989

Effects of dilevalol on renal function.

Renal function was measured in a total of 35 volunteers and patients who were given dilevalol, the R,R optical isomer of labetalol. Young normotensive volunteers (n = 6) and elderly normotensive volunteers (n = 12) received single 400- and 200-mg doses of dilevalol, respectively. Renal function was determined in these subjects on the same day before and after dosing. In addition, patients with mild to moderate essential hypertension (n = 11) and hypertensive patients with renal insufficiency (n = 6) were treated with placebo to establish baseline blood pressure and then were given dilevalol, 400 to 1,600 mg/day, for 2 to 6 weeks until blood pressure was controlled. Renal function was determined at the end of the baseline period and again at the end of dilevalol treatment. A subgroup of elderly hypertensives from the 2 protocols used to study hypertensive patients was treated as a separate study group. The only effect on parameters of renal function seen in any of the study groups was a statistically significant 15% decrease in glomerular filtration rate after single-dose treatment in the elderly normotensive group. Effective renal plasma flow, filtration fraction, renal blood flow and renal vascular resistance were unchanged before and after treatment in all groups. Mean arterial pressure was reduced significantly in all groups except in the elderly normotensive volunteers. Dilevalol appears to be a well-tolerated, effective therapeutic agent that is neutral regarding its effect on renal function and potentially useful in a variety of patient populations.

Adult↗

PubMed1989

The renal function and blood pressure effects of dilevalol in the normotensive and hypertensive elderly.

Dilevalol, the R-R optical isomer of labetalol, is a nonselective beta adrenergic blocking drug with selective beta-2 agonist properties. In a double-blind, crossover study the renal function effects of dilevalol were compared to placebo in 12 normotensive elderly volunteers before and after single dose administration. In addition, chronic treatment (greater than 4 weeks) effects of dilevalol were determined in eight elderly patients with mild to moderate essential hypertension. Renal function was determined by plasma disappearance curves from single injections of 99mTc-DTPA and 131I-orthohippurate. In both study populations renal function tests commenced two hours after dosing at expected peak plasma levels of dilevalol. Normotensive volunteers had an acute decrease in glomerular filtration rate of 10.3 ml/min, which was significant (P less than 0.05), while hypertensive patients had no change in glomerular filtration rate. There were no significant changes in other parameters of renal function measured. In the hypertensive elderly dilevalol treatment resulted in significant reductions, 18 and 19 mmHg respectively, of systolic (P less than 0.01) and diastolic (P less than 0.001) blood pressure. Heart rate was reduced by 5 beats per minute, and the change was not statistically significant. Dilevalol appears to be an excellent agent for treatment of hypertension in the elderly hypertensive patient, and does not change renal function when administered chronically to the hypertensive patient. Small but significant decrements in glomerular filtration rate occur with acute administration to normotensive volunteers.

Aged↗

PubMed1989

Zinc, copper and iron utilisation by chicks fed various concentrations of zinc.

1. Zinc, iron and copper interactions were examined in chicks (New Hampshire X Single Comb White Leghorn) grown individually in stainless steel cages and fed on purified diets with three concentrations of zinc: control (37 mg Zn/kg), moderate (100 mg Zn/kg) and excess (2000 mg Zn/kg) in three studies. 2. Chicks given either moderate or excess zinc excreted more than twice as much 65Zn from a test diet as those fed on the control diet. Thus chicks given the moderate amount of zinc had concentrations of zinc in tissues similar to those of controls but chicks given excess zinc accumulated zinc in their tissues. 3. The specific activity of 65Zn in the tissues, especially in the bursa of Fabricius, of chicks given excess zinc was not reduced as much as would be predicted. Thus, ingestion of excess zinc appeared to reduce tissue turnover of 65Zn, especially in the bursa. However, humoral immune responses, as measured by antibody titres to sheep red blood cells, were not affected. 4. Chicks given excess zinc or pair-fed on the control diet retained less 59Fe from a test diet than chicks given control or moderate concentrations of zinc ad libitum. The iron concentrations in tibiae of chicks given excess zinc were depressed.

Animal Feed↗

PubMed1989

Changes of plasma renin activity and atrial natriuretic factor during intravenous nicardipine treatment of severe hypertension.

Intravenous nicardipine was given to 32 severe hypertensive patients in an increasing dose, titration fashion. Samples for plasma renin activity and plasma atrial natriuretic factor concentration were obtained at the following times: before treatment, at the time of titration response and at the end of a maintenance period. The mean time required to achieve the titration response was 29 min. Plasma renin activity was increased by 32% (p less than 0.05) at the titration response and 181% (p less than 0.005) at the end of an 8-12 h maintenance nicardipine infusion. Atrial natriuretic factor concentration was unchanged from baseline at titration response and was decreased by 25% (p less than 0.005) at the end of maintenance. Mean plasma nicardipine dose was 6.95 mg/h at the titration response and 8.76 mg/h at the end of maintenance. These results suggest that alterations in plasma renin activity and atrial natriuretic factor concentrations may be associated with blood pressure reduction rather than with a direct drug action on release mechanisms.

Atrial Natriuretic Factor↗

PubMed1989

Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing.

Dilevalol, the R-R optical isomer of labetalol, a nonselective beta-antagonist with vasodilation from selective beta 2 agonism, was administered in sequential multiple bolus intravenous injections of 10 to 100 mg in total doses ranging from 35 to 585 mg (mean dose, 414 mg) to 101 patients with supine diastolic blood pressures above 120 mm Hg. Mean blood pressure was reduced from 200 (+/- 3)/129 (+/- 1) mm Hg to 149 (+/- 2)/101 (+/- 1) mm Hg, a mean reduction of 51/28 mm Hg. The therapeutic goal was established as a reduction in supine diastolic blood pressure to less than 100 mm Hg or a reduction of at least 30 mm Hg. This was achieved in 62 (61%) of 101 patients, with an additional 7 patients having a final supine diastolic blood pressure of 100 mm Hg. Treatment with dilevalol was less successful in black male patients than in the group at large. There was a tendency for older patients to respond better than younger patients. Prior recent treatment of patients with beta-adrenergic antagonists decreased the effectiveness of the drug. Significant orthostatic hypotension was not noted. Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy. Dilevalol appears to be a safe and effective drug that can be used intravenously successfully in the majority of patients with severe hypertension and provides an alternative to therapy with other agents. It also is a useful agent for oral treatment of these patients after successful intravenous therapy.

Administration, Oral↗

PubMed1989

Intravenous nicardipine for the treatment of severe hypertension. A double-blind, placebo-controlled multicenter trial.

A placebo-controlled, double-blind multicenter trial was conducted in 123 patients with severe hypertension to examine the efficacy and safety of intravenously administered nicardipine hydrochloride in controlling blood pressure. Seventy-three patients were initially randomized to receive nicardipine treatment. This group had an initial blood pressure of 213 +/- 3/126 +/- 2 mm Hg. Sixty-seven patients achieved the therapeutic goal (diastolic blood pressure less than or equal to 95 mm Hg; systolic blood pressure less than or equal to 160 mm Hg). Fifty patients were randomized to receive placebo solution. Blood pressure in these patients was 216 +/- 3/125 +/- 2 mm Hg. No patient in this group achieved the therapeutic goal during the "blinded" portion of the study. Forty-four of 49 patients who did not respond to placebo administration responded to subsequent treatment with nicardipine. Patients with end-organ damage were included in the study. These included patients with left ventricular hypertrophy, retinopathy, and renal insufficiency. Patients with and without end-organ damage responded equally well to nicardipine treatment. Serious adverse experiences were infrequent, the most common adverse reaction being headache in 24% of the patients studied.

Dose-Response Relationship, Drug↗

PubMed1988

Intravenous dilevalol. Effects of the R-R optical isomer of labetalol in patients with severe hypertension.

Dilevalol hydrochloride, the R-R optical isomer of labetalol hydrochloride, was administered intravenously to subjects with severe hypertension. Twelve subjects with supine diastolic blood pressure of more than 115 mm Hg (mean, 124 +/- 2 mm Hg) were studied. Initial doses of 25 mg of dilevalol administered as a slowly given bolus reduced blood pressure by 14/16 mm Hg. With subsequent additional boluses to a total dose of up to 600 mg, supine diastolic blood pressure was reduced to less than 95 mm Hg in ten of 12 subjects studied (mean reduction, 28 mm Hg). Side effects were minimal and upright blood pressure at the time of reduction of blood pressure to goal was not significantly different from supine blood pressure. Plasma renin activity decreased in 11 of 11 subjects studied. Plasma epinephrine concentrations did not change significantly, whereas plasma norepinephrine concentrations increased 2 1/2-fold, probably reflecting the effect of beta 2-agonism on norepinephrine release. Dilevalol appears to be a safe and effective way of lowering blood pressure short term when intravenous antihypertensive therapy is indicated.

Administration, Oral↗

PubMed1988

Intravenous nicardipine for the treatment of severe hypertension.

PURPOSE: Severe hypertension responds to treatment with nifedipine given orally or sublingually. Nicardipine hydrochloride, a water soluble dihydropyridine analogue similar to nifedipine, has less of a negative ionotropic effect and produces less reflex tachycardia than nifedipine. Our purpose was to assess the antihypertensive efficacy and safety of intravenous nicardipine in a group of patients with severe hypertension (defined as a supine diastolic blood pressure of more than 120 mm Hg). PATIENTS AND METHODS: Eighteen patients with severe hypertension received treatment with intravenous nicardipine. Nicardipine titration was performed using doses of 4 to 15 mg/hour to achieve therapeutic goal (diastolic blood pressure 95 mm Hg or less or decrease in diastolic blood pressure of more than 25 mm Hg). After this therapeutic end-point was reached, patients received maintainance therapy with nicardipine for varying lengths of time: one hour (Group I), six hours (Group II), or 24 hours. When blood pressure control was lost, patients in Groups I and II entered a second maintenance period lasting a maximum of 24 hours. Onset and offset of action of nicardipine at various infusion rates and times of infusion were measured. RESULTS: Onset time to achieve therapeutic response was rapid at 15 mg/hour (0.31 +/- 0.13 hours) when compared with lower doses (1.11 +/- 0.36 hours at 4 mg/hour; 0.54 +/- 0.09 hours at 5 mg/hour; 0.52 +/- 0.09 hours at 7 to 7.5 mg/hour). Those who showed a therapeutic response received maintenance infusions with nicardipine for one (n = 7), six (n = 6), or 24 (n = 5) hours. Sustained blood pressure control at a constant rate of nicardipine infusion was seen in all patients during the maintenance period. After discontinuation of nicardipine, the time for offset of action (increase in diastolic blood pressure of 10 mm Hg or more) was independent of duration of infusion. Decreases in both systolic and diastolic pressures correlated well with plasma nicardipine levels. Heart rate increased by about 10 beats/minute, but this increase did not correlate with plasma nicardipine levels. Side effects were minimal, consisting of headache and flushing. In seven patients, local phlebitis developed at the site of infusion. This occurred after at least 14 hours of infusion at a single site, and the incidence can probably be reduced by shortening the infusion time at a single site. CONCLUSION: Nicardipine appears to be a safe and effective drug for intravenous use in the treatment of severe hypertension.

Adult↗

PubMed1988

Renal function effects of dilevalol, a nonselective beta-adrenergic blocking drug with beta-2 agonist activity.

The effects of dilevalol, a new beta-adrenergic blocking agent with beta-agonism, on renal function were determined in two groups of patients. Patients in group 1, all with normal renal function, received either dilevalol or atenolol. Patients in group II, all with impaired renal function, received either dilevalol or metoprolol. Parameters of renal function determined before and after chronic oral treatment included glomerular filtration rate (GFR), effective renal plasma flow, filtration fraction, mean arterial pressure (MAP), renal blood flow, and renal vascular resistance. Dilevalol lowered MAP by 14 mm Hg (P less than 0.005) in group I and 25 mm Hg (P less than 0.01) in group II but had no effect on other parameters of renal function, at either peak or trough drug levels. Atenolol and metoprolol also lowered MAP by 11 mm Hg (P less than 0.01) and 15 mm Hg (P less than 0.05), respectively. Atenolol reduced GFR by 23% at peak drug level, an effect that was partially ameliorated at trough drug level. The effect of atenolol on GFR appeared to vary as a function of baseline renal function in that greater reductions were seen in groups of patients with increasing baseline GFR. Metoprolol significantly decreased renal vascular resistance by 17% (P less than 0.05). These data suggest that dilevalol effectively lowers blood pressure in hypertensive patients with normal or compromised renal function with no negative impact on parameters of renal function.

Administration, Oral↗

PubMed1988

Characterization of dihydropyridine-sensitive calcium channels in rat brain synaptosomes.

We examined the effects of dihydropyridine Ca2+-channel agonists on synaptosomal voltage-dependent Ca2+ entry and endogenous dopamine release. The (-) isomer of Bay K 8644 and the (+) isomer of Sandoz compound 202-791 were 100-1000 times more potent than their respective opposite enantiomers in enhancing Ca2+ uptake and dopamine release from striatal synaptosomes. The active isomer of each of these compounds increased Ca2+ entry and dopamine release to the same extent at a concentration of 1 nM. Fast-phase Ca2+ entry into synaptosomes isolated from cerebellum, cortex, and hippocampus was sensitive to nanomolar concentrations of Bay K 8644. No effect of Bay K 8644 was observed in synaptosomes isolated from brainstem. Bay K 8644 increased synaptosomal Ca2+ uptake and endogenous dopamine release from striatal synaptosomes only during the initial seconds of KCl-induced depolarization. The greatest increase was observed during the first second of depolarization. No effect was observed after greater than or equal to 5 sec of depolarization. Bay K 8644 did not alter Ca2+ uptake or dopamine release under resting conditions (5 mM KCl) or in response to KCl at greater than 15 mM. The activity of Bay K 8644 was also attenuated by lowering the concentrations of divalent cations in the incubation medium. Agonist activity was observed at Mg2+ concentrations greater than 500 microM (Ca2+ held at 100 microM) and Ca2+ concentrations greater than 100 microM (Mg2+ held at 1000 microM). These results suggest that the Ca2+ channels present in synaptosomes are sensitive to nanomolar concentrations of dihydropyridine agonists under a narrow range of experimental conditions.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1988

Differentiation of ruminal bacterial species by enzyme-linked immunosorbent assay using egg yolk antibodies from immunized chicken hens.

Cross-reactivity among four species of ruminal bacteria was examined by using egg yolk antibodies from immunized Leghorn laying hens and an enzyme-linked-immunosorbent assay. The effects of the four species on the hens were compared on various days postimmunization. Hens injected with the same bacterial species had similar apparent antibody levels over the entire postimmunization period, but only Bacteroides ruminicola B1(4) and Selenomonas ruminantium D antigens elicited early increases in apparent antibody levels during weeks 2 and 3. Antibody cross-reactivity was greatly reduced by week 2, except for antibodies against Streptococcus bovis JB1.

Animals↗

PubMed1988

Improved growth in the progeny of hens immunized with jackbean urease.

Three experiments were conducted with Single Comb White Leghorn and broiler breeder hens. Half of the experimental hens were injected with jackbean urease enzyme and the other half served as uninjected or adjuvant-injected controls. Chicks hatched from urease-injected or control hens were placed factorially (2 x 2) on diets with or without antibiotics. Urease injection of hens resulted in significant improvements in percent fertility and hatch compared with values for control hens. Depending on age, both urease injection and antibiotic feeding stimulated chick growth, independently of one another. Additive effects of these treatments resulted in significant improvements in body weight of chicks injected with urease and consuming antibiotics at all time periods compared with body weights of untreated controls.

Animals↗

PubMed1988

Alterations in phospholipid composition of egg yolks from laying hens fed choline and methionine-supplemented diets.

A trial was conducted to assess the effects of choline and methionine supplementation of the diets of hens on phospholipid composition of egg yolk. By chemical analysis, the basal diet contained 16.6% protein, 1,041 parts per million (ppm) of choline, and .53% TSAA. The energy level was 2,899 kcal ME/kg diet, with no added fat. A rapid isocratic HPLC procedure using a Waters mu Bond-NH2 column (Waters Associates, Milford, MA) was developed to quantify phospholipid components. Analysis of egg samples at peak production (36 wk of age) showed significant (P less than .05) elevations in total phospholipids, phosphatidylcholine (PC), and the ratio of PC to phosphatidylethanolamine (PE), when choline was added at 500 or 1,000 ppm. Phosphatidylethanolamine, in contrast, showed a decline with choline supplementation. Methionine supplementation (125 to 250 ppm) also caused elevations in the total phospholipid composition of the egg yolk but had only modest effects on PC and PE. There was a significant (P less than .05) correlation between the yolk weight and total phospholipid concentration, PC, and the PC:PE ratio. There was a relationship between phospholipid content and weight of eggs when diets of laying hens were supplemented with choline.

Animals↗

PubMed1987

Hematology of Japanese quail selected for high or low serum corticosterone responses to complex stressors.

Blood was collected from random-bred male Coturnix coturnix japonica and from quail selected genetically for high or low serum corticosterone responses to complex stressors after chronic exposure to short daily photoperiods and after exposure to long photoperiods. When compared to the low response quail, high response quail exhibited increased mean cellular hemoglobin values, reticulocyte numbers and heterophil percentages, and decreased monocyte and eosinophil numbers after exposure to long photoperiods. The data indicate that these corticosterone response lines can be partitioned by their hematological responses to photoperiodic manipulation.

Animals↗

PubMed1987

Interaction of dietary antibiotic supplementation and stocking density on broiler chick performance and immune response.

The growth depression caused by reducing the space allowance in battery brooders from 0.047 to 0.019 m2 per chick was ameliorated by subtherapeutic inclusion rates of dietary antibiotics. However, the interaction of antibiotic supplementation and stocking density was not significant for the variables measured. Increasing stocking density improved the efficiency of food utilisation. The high density regimen resulted in decreased weights of the bursa and thymus relative to body weight but there was no concurrent reductions in antibody response, spleen weight or mortality.

Animals↗