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Biomedical subjects

S Anderson

Publications and source records attributed to S Anderson.

At least 523 records · Page 29Linked to original sources
PubMed1984

Beta-adrenergic blockade alone does not decrease renal perfusion in black hypertensives.

We assessed the effects on renal haemodynamics in 18 black patients with essential hypertension of acute and chronic beta-adrenergic blockade with three agents having different properties: atenolol, nadolol or propranolol. Six patients received each drug. In our patients the antihypertensive response to beta-blockers was minimal or nonexistent. This permitted us to analyse the effects on renal haemodynamics of 'pure' beta-blockade, as opposed to the combined effects of beta-blockade and decreased systemic perfusion pressure. In this setting, neither acute nor chronic administration (two months) of each of these agents decreased renal perfusion. We conclude, therefore, that beta-blockade per se has no deleterious effect on renal function and previous observations are most probably accounted for by the blood pressure lowering effect of these drugs, either alone or coupled with beta-blockade of the renal vasculature allowing unopposed alpha-sympathetically mediated vasoconstriction.

Adrenergic beta-Antagonists↗
PubMed1984

Vasodilation mediated by human PTH 1-34 in the spontaneously hypertensive rat.

Parathyroid hormone's cardiovascular effects were assessed in a model of experimental hypertension with known abnormalities of calcium metabolism. Mean arterial pressure (MAP) changes and serum ionized calcium responses were measured in the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto (WKY), following injections of synthetic human PTH 1-34. Six 22-wk-old SHR and six WKY were given intra-arterial serial injections (0.1-100 micrograms/kg) of hPTH 1-34. Both the SHR (P less than 0.001) and WKY (P less than 0.001) demonstrated log dose-dependent hypotensive responses that were maximal at 1 min, with recovery occurring between 15 and 30 min. The slopes, however, of the dose-response curves differed (P less than 0.01). The SHR experienced a greater maximal delta MAP [-93.7 +/- 2.4 (SHR) vs. -71.2 +/- 1.6 mmHg (WKY), P less than 0.01]. Furthermore, the duration of the hypotensive action of hPTH 1-34 was significantly longer (P less than 0.001) in the SHR. Even when corrected for base-line MAP the SHR demonstrated a significant (P = 0.025) enhancement of this vasodilator response at doses of 5 micrograms/kg and greater at time intervals between 3 and 9 min after injection. A transient decrease [2.25 +/- 0.10 (pre) vs. 2.17 +/- 0.11 meq/liter (1 min post), P less than 0.01] in serum ionized calcium occurred at 1 min. We conclude that hPTH 1-34 is a potent vasoactive peptide in both the normotensive WKY and the SHR. The greater maximal hypotensive response to hPTH 1-34 and the prolongation of this cardiovascular effect in the SHR may be an additional manifestation of this experimental animal's acknowledged abnormalities of cellular membrane calcium and phospholipid metabolism.

Animals↗
PubMed1984

Non-steady state placental transfer of highly diffusible molecules.

In twelve experiments performed on five pregnant sheep, uterine and umbilical venous blood samples were drawn in rapid succession following the beginning of a maternal arterial infusion of ethanol and antipyrine. Within a 20 s period the uterine venous ethanol/antipyrine concentration ratio increased from a minimum of 0.3 to 0.7 and the umbilical venous ethanol/antipyrine concentration ratio decreased from a maximum of 3 to 1.2. These results are in agreement with a model of placental exchange showing that the transfer rate of highly diffusible molecules is permeability limited at the beginning of the infusion and then rapidly becomes blood flow limited as the diffusing solutes accumulate in the placenta. The demonstration that the placental barrier is more permeable to ethanol than antipyrine, concomitant with previous demonstrations that the steady state placental clearances of ethanol and antipyrine are nearly equal, supports the hypothesis that in the steady state, the placental clearance of ethanol is blood flow limited.

Animals↗
PubMed1983

Regional cerebral blood flow measurement in rats with radioactive microspheres.

The effect of the method of heart catheterization on the measurement of cerebral blood flow (CBF) with radioactive microspheres was evaluated during various experimental procedures in male Sprague-Dawley rats. Catheters were inserted into the left ventricle via the right carotid or right subclavian artery or directly into the left atrium for microsphere injections. CBF was measured in cerebral cortical and subcortical tissues under control anesthetized (70% N2O, 30% O2), hypoxic or hypercapnic test conditions. Under control conditions, CBF was similar in the right vs the left cerebral hemisphere in subclavian artery and atrial catheterized rats but was greater in the left vs the right cortex in carotid catheterized animals (p less than .05). During hypoxia and hypercapnia CBF increased equally in both cerebral hemispheres in atrial catheterized rats. The increase in CBF was significantly attenuated in the cerebral hemisphere ipsilateral to carotid catheterization during hypoxia and hypercapnia, although the percentage increase in flow was similar in both hemispheres. The results indicate the limitations of measuring regional CBF changes under experimental test conditions in rats with a ligated carotid artery and suggest that atrial catheterization is the method of choice when comparable changes in CBF are desired in both cerebral hemispheres.

Animals↗
PubMed1983

Assignment of segments of the bacteriorhodopsin sequence to positions in the structural map.

Specific amino acid sequence segments have been assigned to locations in the structural map of bacteriorhodopsin using two-dimensional neutron diffraction data and a model building analysis. Models are constructed computationally by building specific regions of the amino acid sequence as alpha helices and then positioning the helices on axes indicated by the density map of Henderson and Unwin (Nature [Lond.]. 1975, 257:28-32). Neutron diffraction data were collected from samples of stacked, oriented "native" purple membranes as well as purple membranes containing different kinds of deuterated amino acids. Models differing in the assignments of helices to specific axes and in rotations of the helices about those axes were tested against the neutron data using a weighted residual factor to rank the models. This residual factor was calculated between observed and predicted intensity differences for pairs of data sets. Using this approach, a small set of related models has been found that predicts the observed intensity changes between five independent data sets. These models are inconsistent with the proposed locations of the retinal chromophore and the carboxyl terminus and with any of the previously proposed models for bacteriorhodopsin.

Amino Acid Sequence↗
PubMed1983

Sites of action of tripamide.

Tripamide is a new diuretic derived from a sulfonamide nucleus that has both antihypertensive and natriuretic properties. We assessed its renal site of effect with standard clearance techniques. Studies during water loading indicated a 47% increase in fractional free water clearance (an effect opposite that of thiazide diuretics) and a simultaneous 75% increase in fractional delivery of solute to the diluting segment. Consequently, when free water clearance was assessed relative to delivery of solute, tripamide induced a decrease from 0.86 +/- 0.03 to 0.75 +/- 0.01. This indicated an inhibitory effect on solute reabsorption at the cortical segment of the thick ascending limb of Henle's loop. Studies during hydropenia indicated increased free water reabsorption. When factored for delivery of solute, however, free water reabsorption decreased from 0.66 +/- 0.02 to 0.61 +/- 0.02, indicating a site of effect of tripamide at the medullary segment of the thick ascending limb of Henle's loop. Tripamide also increased calcium excretion. No effects on renal hemodynamics or indices of effect at the proximal tubule were observed. The data indicate that tripamide is a loop diuretic that may also affect more proximal nephron sites.

Adult↗
PubMed1983

Bumetanide and furosemide.

We assessed the response to and handling of furosemide and bumetanide in 30 experiments with the former and 46 with the latter in normal subjects. Oral doses of furosemide (20, 40, and 80 mg) were used, and subjects received oral doses of 0.5, 1, and 2 mg bumetanide and intravenous doses of 0.5 and 1 mg bumetanide. both drugs were quickly absorbed and peak urinary amounts were reached at 75 min (median). Approximately 30% of an oral dose of each drug was excreted unchanged in the urine with no evidence of dose-dependent elimination. After intravenous injection, 36% of the bumetanide was excreted unchanged. Consequently, bumetanide has an estimated bioavailability of 80% (approximately 40% for furosemide). The relationship between the logarithm of the urinary bumetanide excretion rate and the logarithm of the sodium excretion rate was described by a sigmoid-shaped dose-response curve, with a dose inducing half-maximal response of 1 +/- 0.04 micrograms/min; it was 69.8 micrograms/min for furosemide. Overall, the distinguishing features between the two drugs are the 200% greater bioavailability and the much greater potency of bumetanide.

Administration, Oral↗
PubMed1983

Effects of piretanide in normal subjects.

Piretanide is a new loop diuretic similar to furosemide in pharmacologic properties and approximately six times as potent. We gave 3-, 6-, and 12-mg oral doses to 21 normal subjects and collected serial blood and urine samples for assessment of the drug's kinetics and dynamics. There was no evidence for dose-dependent elimination with the doses we used. Peak serum concentrations and urinary excretion rates appeared between 30 and 60 min. Elimination t1/2s were 60 to 90 min. Approximately 45% of a dose was recovered unchanged in the urine. Renal clearance rate was 90 to 100 ml/min and oral clearance was 200 ml/min. Examination of the relationship between urinary excretion rate of piretanide and sodium excretion allowed determination of potency at the tubular level. The piretanide dose that induced half-maximal response was 12.1 +/- 2.6 micrograms/min; it is 69.8 micrograms/min for furosemide and 1 micrograms/min for bumetanide. Piretanide kinetics, therefore, resemble those of furosemide and bumetanide, but piretanide is five or six times as potent as furosemide and one tenth as potent as bumetanide.

Absorption↗
PubMed1983

Azosemide kinetics and dynamics.

Azosemide is a loop diuretic that may also affect sodium reabsorption at the proximal tubule. We gave intravenous and oral doses of the drug to normal subjects to examine its kinetic and dynamic parameters. In the fasting state a lag time of absorption of approximately 1 hr was followed by absorption t 1/2s and elimination t 1/2s of approximately 0.75 and 2 2.5 hr. Only 2% of an oral dose was excreted unchanged in the urine. After intravenous dosing the elimination t 1/2 was approximately 2 hr; 20% of a dose was recovered unchanged. Thus azosemide has an estimated bioavailability of 10%. The relationship between urinary azosemide excretion rate ("dose") and natriuretic response follows a sigmoid-shaped curve with a dose inducing half-maximal response of 9.3 +/- 2.6 micrograms/min, whereas it is 69.8, 12.1 and 1 microgram/min for furosemide, piretanide, and bumetanide respectively.

Administration, Oral↗
PubMed1983

Isolation of a genomic clone for bovine pancreatic trypsin inhibitor by using a unique-sequence synthetic DNA probe.

Unique-sequence synthetic DNA probes, based on the known amino acid sequence of bovine pancreatic trypsin inhibitor, were constructed from oligodeoxynucleotides. In genomic Southern blot experiments, these probes were shown to hybridize specifically to discrete restriction fragments. A synthetic probe also was used to isolate a cloned BPTI gene from a bovine genomic library. DNA sequence analysis of this clone indicated that the BPTI coding region was neither preceded by a start codon nor immediately followed by a termination codon. This suggests that the mature form of BPTI may be produced through proteolytic processing from a larger polypeptide precursor.

Amino Acid Sequence↗
PubMed1983

Assessment of fat malabsorption.

For the assessment of fat malabsorption, the standard method of measuring faecal fat excretion using a 5 day stool collection has been compared with the alternative methods: stool microscopy, a lipid tolerance test and a continuous marker technique for the estimation of fat content on a single stool sample. The lipid test, using an emulsion of arachis oil (Prosparol), was less reliable than had been expected with a sensitivity of 33% and a specificity of 45.4%. Stool microscopy using Oil Red O to stain fat globules had a sensitivity of 72.2% and a specificity of 95.4%. Fat estimation of a single stool sample using copper (1) thiocyanate showed a high correlation with that determined on a 5 day stool collection (p less than 0.001). It is concluded that lipid tolerance tests have little place in the estimation of fat absorption. In laboratories where faecal fats are not measured, microscopic examination of stool for fat globules provides a specific and relatively sensitive method for detecting steatorrhoea. The use of a continuous marker provides a method for assessing the degree of steatorrhoea on a single stool sample without the disadvantages of the conventional method of faecal fat analysis.

Celiac Disease↗
PubMed1983

Nephron site of effect of nonsteroidal anti-inflammatory drugs on solute excretion in humans.

Indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) decrease solute excretion when administered acutely to normal subjects. We performed clearance studies during water loading of 10 normal volunteers and during hydropenia in eight additional subjects to determine the nephron site of this effect using indomethacin and carprofen as inhibitors of prostaglandin (PG) synthesis. Their administration decreased fractional excretion of sodium, chloride, and volume. During water loading, fractional clearance of free water decreased from 0.13 +/- 0.04 during the control study to 0.09 +/- 0.03 and 0.06 +/- 0.02 with indomethacin and carprofen, respectively. However, fractional delivery of solute to the dilution segment decreased in parallel such that free water clearance corrected for delivery did not change with either drug. In humans, therefore, the decrement in solute excretion that occurs with administration of NSAIDs occurs prior to the diluting segment. During hydropenia, free water reabsorption relative to osmolar clearance increased (P less than 0.01). In both studies, neither the marker of renal perfusion or of proximal nephron function changed with inhibition of PG synthesis. The data indicate that at the tubular level, NSAIDs increase solute reabsorption at the medullary segment of the thick ascending limb of the loop of Henle. Therefore, a physiologic role of renal prostaglandins at this nephron site is implied.

Anti-Inflammatory Agents↗
PubMed1983

Hemodynamic and neuroendocrine responses to acute and chronic alpha-adrenergic blockade with prazosin and phenoxybenzamine.

We investigated the relevance of the selective alpha 1-adrenergic receptor blockade produced by prazosin to its blood pressure-lowering efficacy in man. The hemodynamic and neuroendocrine responses to the acute and chronic oral administration of prazosin and phenoxybenzamine were compared in a randomized, double-blind, placebo-controlled, crossover study of 11 patients with essential hypertension. These responses were also evaluated during lower body negative pressure and dynamic bicycle exercise, which produce potent but diversified activation of the sympathetic nervous system. In the acute studies, arterial blood pressure decreased to similar levels with prazosin or phenoxybenzamine; however, hemodynamic and neuroendocrine responses differed both before and during sympathetic nervous system activation. Prazosin lowered arterial blood pressure by reducing total peripheral resistance (p less than 0.05). In contrast, phenoxybenzamine produced a modest reduction in cardiac output (8%, p less than 0.05) with little change in total peripheral resistance, forearm vascular resistance or forearm blood flow. Additionally, plasma norepinephrine concentration and heart rate rose to significantly higher levels with prazosin (p less than 0.02) than with phenoxybenzamine, a difference that was most evident with lower body negative pressure or dynamic exercise. Baroreceptor control of arterial pressure homeostasis was preserved with both agents, except during marked degrees of cardiovascular stress. With chronic therapy, the circulatory responses adapted to the alpha-adrenergic antagonists, and both drugs produced similar hemodynamic and neuroendocrine profiles. The differences with acute administration may be the result of a more rapid onset of action and a more marked degree of alpha-adrenergic blockage with prazosin than with phenoxybenzamine therapy, rather than to any difference in their alpha 1- and alpha 2-adrenergic receptor blocking properties. Moreover, the findings of the present study suggest that the prejunctional alpha 2-receptor, autoinhibitory to sympathetic neuronal norepinephrine release, is of no functional significance in patients with essential hypertension.

Adrenergic alpha-Antagonists↗
PubMed1983

Acute effects of grain dust exposure during a work shift.

We studied 248 grain handlers and 192 city services workers (control subjects) before and after an 8-h work shift and measured total dust levels using personal samplers. We found that grain workers exposed to a mean total dust level of 3.3 +/- 7.0 mg/m3, when compared with control subjects, had (1) a higher prevalence of work-related respiratory symptoms (p less than 0.05) and significant decrements in forced-expiratory volume in one second (FEV1) and maximal flow rates after exhalation 50 and 75% of forced vital capacity (Vmax50 and Vmax75) during the work shift, and (2) significant differences (p less than 0.05) in preshift/postshift percent changes in forced vital capacity (FVC), Vmax50 and Vmax75. Adjusting for age, height, and smoking habit, grain handling still had a significant negative effect on FVC, Vmax50, and Vmax75. In grain workers, we found a significant (p less than 0.05) negative relationship between total dust levels and the percent change in FVC, Vmax50, and Vmax75 and a positive relationship between dust level and percent change in leukocyte counts. Grain workers' perception of dust level correlated with the measured dust level and the prevalence of symptoms. Occupational exposure to grain dust during a work shift has a dose-related adverse acute respiratory effect regardless of smoking habit, atopic status, or age, and it produces a dose-related leukocyte response at total dust levels below 15 mg/m3.

Acute Disease↗