Search PubMed⌕ Search

Biomedical subjects

R D Smith

Publications and source records attributed to R D Smith.

At least 361 records · Page 20Linked to original sources
PubMed1986

Effects of nitroglycerin, dipyridamole, nifedipine, verapamil and diltiazem on canine coronary arterial rings contracted with 5-hydroxytryptamine and anoxia.

Anoxia has been shown to potentiate the constrictor effects of 5-hydroxytryptamine (5HT) in isolated vascular tissue. In the present study, canine coronary arterial rings were incubated with various treatments and exposed to 5HT (4 X 10(-7) M) and anoxia (95% N2 and 5% CO2). Developed tension was increased by 250 +/- 40 mg by 5HT alone and 2,000 +/- 90 mg by 5HT and anoxia. Calcium (5 mM) potentiated, while inorganic (lanthanum, 10(-2) M) and organic calcium antagonists (nifedipine, verapamil and diltiazem; IC50 = 7 X 10(-9), 7.3 X 10(-8) and 2.4 X 10(-7) M, respectively) blocked the anoxic potentiation. Anoxia alone decreased resting tension (RT). Methysergide 3 X 10(-5) M inhibited both the 5HT- and anoxia-potentiated responses. Nitroglycerin decreased RT and inhibited the anoxic response (IC50 = 7.6 X 10(-6) M), while dipyridamole decreased RT and did not affect the anoxic response. These data suggest that the potentiation of 5HT contraction by anoxia is dependent upon extracellular calcium influx and is linked to a 5HT receptor. In addition, inhibition of the anoxic response can be achieved at other sites and is not a property common to all coronary vasodilators.

Animals↗
PubMed1986

A comparison of enalapril plus hydrochlorothiazide with standard triple therapy in renovascular hypertension.

This prospective, double-blind, multicenter study compared enalapril plus hydrochlorothiazide with standard triple therapy (STT; hydrochlorothiazide, timolol, and hydralazine) with regard to safety, tolerability, antihypertensive efficacy, and effect on renal function in 75 patients with documented renovascular hypertension. Both groups showed a significant mean decrease in systolic and diastolic blood pressure during the double-blind study, with the enalapril group showing a mean 12 mm greater decrease in systolic blood pressure as compared to STT (less than 0.05). Effective treatment of diastolic hypertension was noted in 96% of the enalapril group as compared to 82% on STT (p less than 0.05). STT failure was seen exclusively in patients with bilateral renal artery stenosis of high grade and frequently in association with impaired renal function. cPAH, a measure of effective renal plasma flow, showed a significant increase in the enalapril group, as compared to the STT (p less than 0.05). In contrast, there was a bimodal response of CIn (GFR): 80% of patients in the enalapril group showed no significant change while 20% (10 patients) showed a mean decrease of 28% along with a 12% increase in CPAH (p less than 0.01). No acute renal failure or toxic side effects were noted in the enalapril group. Enalapril plus hydrochlorothiazide is very effective in treating renovascular hypertension and is without significant toxic side effects. The self-limited increase in serum creatinine seen in 20% of renovascular hypertensive patients receiving enalapril and hydrochlorothiazide may identify a subset of patients with unilateral or bilateral high grade renal artery stenosis who should be treated with angioplasty or operative intervention.

Adult↗
PubMed1986

The antagonist and partial beta agonist properties of celiprolol in isolated rat cardiac tissue.

Celiprolol was evaluated for its antagonist and partial beta agonist effects in rat spontaneously beating right atria and in electrically stimulated left ventricular strips. Celiprolol, like propranolol, produced a parallel concentration-related rightward shift of the isoproterenol (ISO) (beta agonist) concentration-response curve without decreasing the maximum response in rat right atria. The pA2 values for celiprolol and propranolol were 7.02 +/- 0.30 and 8.45 +/- 0.29, respectively. Unlike propranolol, however, celiprolol increased the resting spontaneous rate at concentrations 3 X 10(-7) to 10(-4)M. ISO alone produced a concentration-related increase in heart rate of rat right atria (maximum 149 +/- 15 bpm at 3 X 10(-7)M). Whereas, celiprolol increased atrial rate a maximum of 49 +/- 5 bpm at 10(-6)M. ISO produced a concentration-related increase in the developed tension of rat right ventricular strips (maximum 79 +/- 4% at 10(-6)M. Celiprolol, by contrast, had no effect on developed tension in concentrations up to 10(-3)M. In separate experiments, celiprolol alone increased right atrial rate a maximum of 40 +/- 6 bpm at 10(-5)M. Pretreatment with propranolol (10(-6)M) completely blocked the increase in rate. It is concluded that celiprolol is a potent and competitive beta antagonist and a partial agonist with approximately 33% of the efficacy (comparing maximum stimulating concentrations) and 0.01 the potency of ISO in rat right atria (at ED50 concentrations). Celiprolol, however, unlike ISO, has no inotropic effect in rat ventricular strips suggesting possible differences in their agonist properties.

Adrenergic beta-Agonists↗
PubMed1986

Evaluation of alpha-adrenergic cardiac stimulation in anesthetized dogs: can this play a role in propranolol insensitive cardiostimulatory effects of celiprolol.

The role of alpha-adrenergic systems in modulating contractility and rate in the canine heart is not completely understood. This was evaluated by examining alpha-agonists and antagonists in ganglionic- and beta-blocked, anesthetized dogs. Also, partial agonist effects of the beta-blocker celiprolol in the ganglionic blocked dog are insensitive to propranolol and may be mediated via alpha-2 antagonism. Prazosin (0.3 mg/kg), yohimbine (0.3 mg/kg), celiprolol (3 mg/kg) and vehicle were administered to ganglionic-(mecamylamine 2 mg/kg) and beta-adrenergic-(propranolol 1 mg/kg + 0.3 mg/kg/hr) blocked dogs. Clonidine (0.3 and 3.0 micrograms/kg), phenylephrine (3 micrograms/kg) and norepinephrine (0.3 microgram/kg) produced significant increases in arterial pressure with minimal chronotropic or inotropic effects. Celiprolol produced sustained increases in heart rate and contractile force of 15 +/- 3 beats/min and 33 +/- 7 percent (X +/- SEM) without significant vascular alpha antagonism. Yohimbine, prazosin and vehicle were without significant chronotropic or inotropic effects. However, yohimbine and prazosin selectively reduced pressor responses to clonidine and phenylephrine, respectively. In further studies adding prazosin or phentolamine before treatment with celiprolol did not attenuate its effects on heart rate and contractility. These results do not support significant inotropic or chronotropic effects of alpha-adrenergic receptor modulation in anesthetized dogs. The cardiac stimulatory effects of celiprolol do not appear to be mediated via cardiac alpha receptors.

Adrenergic beta-Antagonists↗
PubMed1986

Celiprolol, a compound possessing weak alpha 2-adrenergic antagonist properties in the dog.

Studies were conducted to evaluate the effects of celiprolol on alpha-adrenergic stimulation of dog saphenous vein rings (postsynaptic effect) and on catecholamine outflow from the dog coronary circulation during sympathetic nerve stimulation in vivo (presynaptic effect). In venous rings, celiprolol, 10(-6) to 10(-4) M, shifted the concentration-response curve to BHT 920 in a concentration-related manner, but had no effect on the response to methoxamine at concentrations less than 10(-4) M. During continuous stimulation of the right stellate ganglion, celiprolol, 1-10 mg/kg i.v., increased the catecholamine concentration in the coronary sinus, while decreasing heart rate. In contrast, propranolol did not affect catecholamine concentration but decreased heart rate, rauwolscine increased both catecholamine concentration and heart rate, and clonidine decreased both catecholamine concentration and heart rate. These results are consistent with the hypothesis that celiprolol possesses weak alpha 2-antagonist properties in addition to its beta 1-blocking activity.

Adrenergic alpha-Agonists↗
PubMed1986

Medical education and its impact on the future of pathology.

The impact of changes in medical education on the future of pathology are examined by analyzing how recommendations in the GPEP report may affect pathology practice. For pathologist teachers, there will be increasing involvement with students during the clinical years of the curriculum and emphasis on new course material particularly related to the problems of aging, environmental pathology, and principles of prevention. The hospital pathologist will have a leadership role in introducing computer technology and will become increasingly involved in ambulatory and outrearch services. Pathologists will become more involved in the continuing education of other physicians, particularly with emphasis on using the laboratory to solve specific problems utilizing new technologies, new areas of testing, and the pathologist as a consultant.

Clinical Competence↗
PubMed1986

Isolate of Anaplasma marginale not transmitted by ticks.

The tick-borne transmissibility of 2 isolates of Anaplasma marginale was compared. Dermacentor variabilis were exposed to A marginale as nymphs by feeding on 1 of 4 splenectomized calves during periods of ascending parasitemia (maximum 49% to 81% parasitized erythrocytes) induced by injection of a stabilate. Tick-borne transmission was attempted, using 26 to 224 adult ticks within 30 to 220 days after molting. Adult D variabilis did not transmit an Illinois isolate of A marginale in 7 tick-borne transmission experiments (P = 0.0047), including 2 experiments in which calves were inoculated IV with homogenates of adult ticks. In contrast, a Virginia isolate of A marginale was readily transmitted by the same tick colony. Thus, previously reported morphologic and immunologic differences among A marginale isolates may extend to tick-borne transmissibility. The Virginia and Illinois A marginale isolates had an inclusion appendage that was not a marker for tick transmissibility.

Anaplasmosis↗
PubMed1986

Identification of antigens of two isolates of Anaplasma marginale, using a western blot technique.

Antigens of the Illinois (IAM) and Florida (FAM) isolates of Anaplasma marginale were analyzed, using the western blot technique and antiserum from A marginale-infected calves. Crude antigens were prepared from the parasitemic blood of each. Antiserum was collected after the primary and recrudescent parasitemias. Antigens were separated, using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Antigens were then transferred onto nitrocellulose membranes and exposed to test sera. Antibodies attached to the membrane-bound antigens were detected, using an avidin/biotin peroxidase assay and biotinylated rabbit anti-goat immunoglobulin G. Antigens detected were of a high molecular weight group (108 to 91 kilodaltons [kd]) or of a low molecular weight group (47 to 27 kd). The IAM antigens were 100 kd, 96 kd, 47 kd, 38 to 43 kd, and 27 kd; these antigens were detected, using anti-IAM and anti-FAM antibodies, but the anti-FAM antibodies had a strong reaction to only the 100-kd and 38- to 43-kd antigens of IAM. The FAM antigens were 108 kd, 91 kd, 47 kd, 38 to 43 kd, and 27 kd; these antigens were detected, using anti-FAM antibodies and, except the 91 kd antigen, anti-IAM antibodies. Because the 91-kd antigen was detected only in the FAM antigen and detected only by sera from FAM-infected calves, this isolate-specific antigen may be associated with the ability of FAM to induce disease in an IAM-immune animal. Sheep anti-A ovis antibodies reacted only to the 38- to 43-kd antigens of each isolate, indicating that these antigens may be genus-specific.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaplasma↗
PubMed1985

Comparison of effects of enalapril plus hydrochlorothiazide versus standard triple therapy on renal function in renovascular hypertension.

Renal function and antihypertensive drug efficacy were determined in a prospective, double-blind, multicenter study comparing enalapril plus hydrochlorothiazide with standard triple therapy (hydrochlorothiazide, timolol, and hydralazine) in 75 patients with documented renovascular hypertension. Both groups had significant mean decreases in systolic and diastolic blood pressures. Effective control of diastolic hypertension occurred in 96 percent of patients receiving enalapril compared with 82 percent of patients receiving the triple-drug regimen. Effective renal plasma flow was significantly increased by enalapril therapy. In contrast, the glomerular filtration rate had a bimodal response. In 80 percent of enalapril-treated patients, there was no significant change in the inulin clearance, although in 20 percent of patients (10), there was a 28 percent decrease in the inulin clearance with a concomitant 12 percent increase in renal plasma flow. Seven of the 10 patients had unilateral renal artery stenosis, but in all 10, it was high-grade stenosis (more than 80 to 90 percent stenosis). Although a significant rise in the serum creatinine level occurred in one patient in association with diuretic therapy, volume repletion reversed this azotemia. No oliguric acute renal failure occurred in the enalapril-treated group. The cause of the decrease in glomerular filtration rate induced by enalapril plus hydrochlorothiazide in a minority of patients with renal artery stenosis appears to be quite complex. Although the abolishment of the autoregulation of glomerular filtration secondary to blockage of angiotensin II appears to be a primary cause, the roles of decreased arterial pressure, renal counterbalance, concurrent diuretic therapy, and other hemodynamic factors that may maintain glomerular ultrafiltration pressure must also be considered. The results of this study show that enalapril plus hydrochlorothiazide is effective in treating renovascular hypertension. Special care is needed for a small group of patients with renovascular hypertension in whom there is a decrease in the glomerular filtration rate with this therapy. This may identify a subset of patients with unilateral or bilateral high-grade renal artery stenosis in whom alternative therapy--percutaneous angioplasty or surgical intervention--may be considered.

Adult↗
PubMed1985

Sequential alterations in globin gene chromatin structure during erythroleukemia cell differentiation.

During differentiation of murine erythroleukemia cells, adult beta-globin gene chromatin acquires site-specific, DNase I hypersensitivity and an increased sensitivity in the globin gene region toward micrococcal nuclease (MNase) digestion. The relationship of these changes in chromatin structure to globin gene activation and to cellular commitment events has been studied. Imidazole, which blocks globin gene transcription during induction does not affect the terminal differentiation of the cells nor does it prevent the acquisition of DNAse I hypersensitivity. The formation of the inducible DNase I-hypersensitive site near the globin gene accompanies the developmental events which lead to cellular differentiation independent of the transcription process. The increased MNase sensitivity of the adult beta-globin gene region, normally preceded by the acquisition of 5' DNase I hypersensitivity, was blocked by the addition of imidazole prior to but not after globin gene activation. The enhanced MNase sensitivity was not abolished by the addition of actinomycin D and, thus, reflects a part of chromatin alterations that define potential for transcription. Therefore, there is a sequential series of chromatin alterations in the globin gene region associated with murine erythroleukemia cell differentiation. The appearance of the inducible 5' DNase I-hypersensitive site precedes the onset of globin gene transcription and is strongly correlated with commitment events. The enhanced MNase sensitivity is closely related to globin gene transcription, but it is not a consequence of the transcription process. In addition, the commitment of cells to terminal differentiation is dissociable from the stimulation of globin gene transcription.

Acetamides↗
PubMed1985

Effects of a stable prostaglandin analogue, L-644,122, in healthy and hypertensive men.

L-644,122 is a chemically stable vasodilator prostaglandin analogue. It is a selective renal vasodilator in dogs. The object of the present study was to determine whether it increases effective renal plasma flow (ERPF) in man. L-644,122 was administered intravenously to 4 healthy volunteers and by mouth to 4 mild hypertensives. It did not increase ERPF. Instead it acted as a non-specific vasodilator, lowering diastolic blood pressure and increasing heart rate. An unexpected increase in glomerular filtration rate (19% greater than placebo) after low dose intravenous L-644,122 merits further study.

Administration, Oral↗
PubMed1985

Duration of retained fetal membranes and subsequent fertility in dairy cows.

Lactations from 1,111 heifers and 2,493 cows were evaluated for the effects of the duration of retained fetal membranes on subsequent fertility. Cows or heifers with metritis, ovarian cyst, both metritis and cyst, or neither were evaluated in separate strata in order to control for the effects of parity, metritis, and cyst on fertility. Duration of retention had no effect on fertility if an animal had metritis or cyst. There was a suggestion that retained fetal membranes in heifers free of metritis and cyst decreased conception rate at first service. In multiparous cows free of metritis and cyst there was a significant decrease in conception rate at first service when retention exceeded 5 days, and delays of +18 days to 1st service and +57 days to conception when retention exceeded 7 days.

Journal Article↗
PubMed1985

Rapid and high resolution capillary supercritical fluid chromatography (SFC) and SFC/MS of trichothecene mycotoxins.

The potential application of capillary column supercritical fluid chromatography (SFC) and SFC/mass spectrometry (SFC/MS) for the separation and analysis of mycotoxins of the trichothecene group was examined. Trichothecenes present significant analytical problems for both gas and liquid chromatography with a major difficulty for the latter being the lack of sufficiently sensitive and selective detectors. Supercritical carbon dioxide mobile phases at temperatures up to 100 degrees C were used with deactivated fused silica columns coated with crosslinked stationary phases. Separations were obtained under pressure ramped conditions using long (15 m) 50-micron i.d. columns for several trichothecenes (diacetoxyscirpenol, deoxynivalenol, and T-2 toxin) and related higher molecular weight macrocyclic (roridin and verrucarin) trichothecenes. In addition, new rapid pressure programming techniques with short (less than 2m) 25- to 50-micron i.d. capillary columns were used to obtain fast separations in as little as 1 min. SFC/MS with ammonia chemical ionization provided high selectivity and sensitive detection (with approximately 1-pg detection limits) for trichothecene mixtures. The extension to complex sample matrices is discussed and the application of selective MS/MS detection is demonstrated.

Chemical Phenomena↗
PubMed1985

Management factors affecting reproductive performance of dairy cows in the northeastern United States.

Dairy herds (476) in seven states in the northeastern United States were surveyed to determine effects of various management factors on reproductive performance. Error of estrus detection (greater than 1 ng/ml of milk progesterone) on the day of service was 5.1% for 4558 cows but was as high as 60% in some herds. Error was not affected by herd size but was greater in freestall (6.8%) than in conventional (5.2%) housing. "Standing" and "riding other cows" were the most accurate signs of estrus. Of cows in or near estrus when serviced, 28.1% were open 3 wk later, 12.9% were probably open, and 59% were probably pregnant based on analysis of milk progesterone. Conception rate, not affected by herd size or housing type, was greater for cows in estrus during the morning and serviced the same afternoon (52.2%) than for cows observed in the afternoon and serviced the next morning (47.1%). Fifty-five percent of cows open to first service were serviced again within 3 days of expected return to estrus. Days to first service and conception rates were correlated positively. Milk progesterone concentration 21 to 24 days after service predicted a cow will calve with 88.6% accuracy and that she will not with 93.9% accuracy. Veterinarians predicted a calf with 92.5% accuracy by rectal palpation.

Animal Husbandry↗
PubMed1985

Path analysis of dry period nutrition, postpartum metabolic and reproductive disorders, and mastitis in Holstein cows.

Path analysis and logistic regression were used to model direct and indirect relationships among clinical periparturient (within 30 d after calving) retained placenta, metritis, veterinary-assisted dystocia, uncomplicated and complicated ketosis, left displaced abomasum, parturient paresis, mastitis, and estimated nutrient intakes (protein, calcium, phosphorus, energy; coded into terciles) in the last 3 wk of the dry period. Data were from 1,374 multiparous Holstein lactations for calvings from March 1981 through February 1982 in 31 commercial herds in central New York. Periparturient disorders occurred as a complex. Odds ratios for the multiplicative effects of parturient paresis on incidence of veterinary-assisted dystocia, retained placenta, complicated ketosis, and clinical mastitis were 7.2, 4.0, 23.6, and 5.4, respectively. Reproductive disorders were interrelated. Retained placenta, left displaced abomasum, and parturient paresis directly increased risk of complicated ketosis (odds ratios were 16.4, 53.5, and 23.6, respectively). Higher terciles of estimated energy intake in the last 3 wk of the dry period decreased risk of veterinary-assisted dystocia and left displaced abomasum, while higher terciles of estimated protein intake decreased risk of retained placenta and uncomplicated ketosis. Estimated nutrient intakes were directly related to subsequent metabolic disorders and directly and indirectly related (mediated by metabolic disorders) to reproductive disorders. The study suggests that feeding higher intakes (relative to National Research Council recommendations) of protein and energy in the last 3 week of the dry period may reduce the incidence of metabolic and reproductive disorders. Exact recommendations as to the amounts and types of feed cannot be made from our results.

Animal Nutritional Physiological Phenomena↗
PubMed1985

Path model of reproductive disorders and performance, milk fever, mastitis, milk yield, and culling in Holstein cows.

Path analysis was used to model the direct and indirect relationships among age, previous lactation yield or estimated transmitting ability for milk, body weight, days dry, reproductive disorders, milk fever, mastitis, reproductive performance, current milk yield, and culling. Prospective data were from 784 primiparous and 2,066 multiparous Holstein lactations from 33 herds. Heifers that were older, of lighter weight, or who had lower estimated transmitting ability for milk had more problems, less milk, and poorer survival. Dystocia in heifers had several detrimental consequences including 2.9 to 4 times more retained placenta, metritis, and culling and +7.4 d more to first service. Cystic ovaries were associated directly with 376 kg greater milk yield and with a 16.5-d delay in first service. Failure to conceive at first service and mastitis increased risk of culling 5.2 to 10 times. In multiparous cows, milk fever increased risk of reproductive disorders by 1.6 to 4.2 times and indirectly contributed to poor breeding performance and increased culling. Risk of culling was increased 2.1 to 3.7 times directly by mastitis and dystocia and by poor breeding performance.

Age Factors↗