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Biomedical subjects

R A Preston

Publications and source records attributed to R A Preston.

At least 73 records · Page 4Linked to original sources
PubMed1991

Classic therapeutic trials in hypertension. Were patients vulnerable to unsuppressed peak morning blood pressure?

A metaanalysis of the major clinical trials on the benefits of antihypertensive therapy revealed that there is an overall reduction of coronary events by treatment, but that it is only about one-half of the reduction predicted. The reduction in stroke achieved the predicted number. This "failure" has been attributed to study design, patient age at entry, preexisting disease, high-lipid diets, drug-associated cardiac dysrhythmias, and the "J-curve" effect. It is also possible that the drugs used in these trials did not suppress the morning acceleration of blood pressure during which most coronary and cerebrovascular events occur. Ambulatory blood pressure monitoring studies suggest that antihypertensive drugs reduce overall blood pressure throughout the 24-h period, but do not change the circadian curve. The beneficial effect of antihypertensive therapy probably rests with the magnitude of blood pressure reduction. It is unlikely that lack of suppression of morning acceleration alone accounted for the failure of "older" drugs to prevent as much cardiac mortality as expected.

Aged↗
PubMed1990

Facial nerve injury and hemifacial spasm.

We studied evidence of facial nerve damage in patients with hemifacial spasm. Three types of evidence of nerve damage were analyzed: objectively measured weakness in eyelid protractor strength, clinically evident weakness of muscles innervated by the seventh nerve, and clinically evident aberrant seventh nerve regeneration. Of the 60 patients in the study, 54 (90%) had at least one of these features of seventh nerve damage. Objectively measured eyelid protractor weakness was noted in 27 of 58 patients (47%) who were tested. Clinically apparent weakness of at least one of four facial muscle groups was noted in 42 of 60 patients (70%). Aberrant seventh nerve regeneration was documented in 25 of 60 patients (42%). These findings indicate that facial nerve damage is common in patients with hemifacial spasm.

Adult↗
PubMed1990

Renal biopsy in patients 65 years of age or older. An analysis of the results of 334 biopsies.

We studied the clinical and pathological data for 334 patients age 65 or more who underwent renal biopsy for acute renal failure (ARF, n = 55), subacute renal failure (SRF, n = 72), chronic renal failure (CRF, n = 57), proteinuria (n = 137), and hematuria (n = 13). Tissue diagnoses were glomerulopathy (n = 252, 75.4%), acute tubular lesions (n = 18), interstitial nephritis (n = 23), vascular diseases (n = 36, including 14 with cholesterol emboli), and five miscellaneous diagnoses. Of the 55 patients with ARF, 23 had a glomerular lesion, 15 had acute tubular necrosis, and 8 had acute interstitial nephritis. Of 72 patients with SRF, 49 had a glomerulopathy, 12 had a vascular disorder, and six had acute interstitial nephritis. Hence, patients with ARF or SRF exhibited a high potential for reversible lesions. Only 11.3% of patients with CRF had potentially reversible causes. The most common causes of proteinuria were membranous glomerulopathy (34.3%), minimal change disease (14.6%), focal segmental sclerosis (11.7%), and amyloidosis (8.8%). Of the 25 patients with advanced nephrosclerosis, 24 had renal failure, 20 were hypertensive, and 13 had cholesterol emboli. Of 33 patients with diabetes mellitus, 66.7% were found to have lesions not related to diabetes. We conclude that renal biopsy is most useful in older patients with ARF or SRF because of potentially reversible renal disease. Old age alone is not a contraindication to performing a renal biopsy.

Acute Kidney Injury↗
PubMed1990

Role of vacuolar acidification in protein sorting and zymogen activation: a genetic analysis of the yeast vacuolar proton-translocating ATPase.

Vacuolar acidification has been proposed to play a key role in a number of cellular processes, including protein sorting, zymogen activation, and maintenance of intracellular pH. We investigated the significance of vacuolar acidification by cloning and mutagenizing the gene for the yeast vacuolar proton-translocating ATPase 60-kilodalton subunit (VAT2). Cells carrying a vat2 null allele were viable; however, these cells were severely defective for growth in medium buffered at neutral pH. Vacuoles isolated from cells bearing the vat2 null allele were completely devoid of vacuolar ATPase activity. The pH of the vacuolar lumen of cells bearing the vat2 mutation was 7.1, compared with the wild-type pH of 6.1, as determined by a flow cytometric pH assay. These results indicate that the vacuolar proton-translocating ATPase complex is essential for vacuolar acidification and that the low-pH state of the vacuole is crucial for normal growth. The vacuolar acidification-defective vat2 mutant exhibited normal zymogen activation but displayed a minor defect in vacuolar protein sorting.

Amino Acid Sequence↗
PubMed1989

Assay of vacuolar pH in yeast and identification of acidification-defective mutants.

As part of a genetic analysis of the biogenesis and function of the vacuole (lysosome) in the yeast Saccharomyces cerevisiae, assays of vacuolar pH were developed and used to identify mutants defective in vacuolar acidification. Vacuoles were labeled with 6-carboxyfluorescein with the membrane-permeant precursor 6-carboxyfluorescein diacetate. Dual-excitation flow cytometry was used to calibrate the pH-dependence of 6-carboxyfluorescein fluorescence in vivo. Vacuoles in wild-type yeast were mildly acidic, pH 6.2, in cells grown under several different conditions. Cultures labeled with 6-carboxyfluorescein were screened by fluorescence-ratio microscopy to detect mutants that had defects related to vacuolar acidification. A recessive nuclear mutation, vph1-1, caused an abnormally high vacuolar pH of 6.9, as assayed by flow cytometry, and eliminated vacuolar uptake of the weak base quinacrine. Acidification in a pep12::LEU2 mutant appeared defective by fluorescence-ratio microscopy and quinacrine-uptake assays, but the vacuolar pH in the pep12::LEU2 mutant was nearly normal (pH 6.3) in flow cytometric assays.

Hydrogen-Ion Concentration↗
PubMed1989

Newer principles of patient profiling for antihypertensive therapy.

The mosaic of essential hypertension seems to be gaining new tiles at an accelerating rate. Of the many pathophysiological factors and markers for the factors that can be considered as possible elements of a profiling algorithm, there are relatively few with solid data to support their use. Use of plasma renin activity for prospective profiling does not appear to be valid for individual patients. It remains useful for diagnosis of renal artery stenosis and primary aldosteronism. The black race does have some well-documented pathophysiological differences from the white race regarding hypertension, and there are some useful data bits for selecting specific therapy. The elderly, obese patients, and young patients with hyperdynamic circulation appear to have enough group characteristics to enable selection of drugs more targeted to their needs. Anxious patients who often display symptoms that mimic pheochromocytoma symptoms comprise a unique group. One of the largest groups is patients with hypertension plus one or more concomitant diseases. Finally, drug selection decisions must also consider the effect of drugs on serum lipoproteins, left ventricular hypertrophy and vascular compliance, sexual function and other quality of life issues, and cost.

Age Factors↗
PubMed1988

Acute rhabdomyolysis associated with cocaine intoxication.

Because an increasing number of patients were arriving at our emergency room with cocaine intoxication and rhabdomyolysis, we reviewed our experience with such patients. We identified 39 patients seen at our institution over an eight-year period with acute rhabdomyolysis after cocaine use. The patients' mean creatine kinase level was 12,187 U per liter (range, 1756 to 85,000). Thirteen of the 39 patients (33 percent) had acute renal failure; 6 of them died. In comparison to the patients with normal renal function, those with renal failure were more often admitted with profound hypotension (46 vs. 4 percent; P less than 0.001), hyperpyrexia (69 vs. 15 percent; P less than 0.001), and markedly elevated serum creatine kinase levels (mean, 28,084 vs. 7931 U per liter; P less than 0.01). Disseminated intravascular coagulation developed in seven patients with renal failure. All six deaths were in this group. Severe hepatic dysfunction was found in 11 patients with renal failure. We conclude that cocaine intoxication can cause acute rhabdomyolysis with acute renal failure, severe liver dysfunction, and disseminated intravascular coagulation and that the mortality rate among patients with this syndrome is high.

Acute Disease↗
PubMed1988

Functional relationships between L- and D-alanine, inosine and NH4Cl during germination of spores of Bacillus cereus T.

The results of a physiological study of the interaction between NH4Cl, inosine, and the stereoisomers of alanine during germination of spores of Bacillus cereus T are presented. Detailed kinetics for the germination of unheated spores in moderate concentrations of L-alanine (in the absence of auto-inhibition due to alanine racemase) are established, as is the specificity of the stimulatory effect of NH4Cl in relation to other salts, amines, and germinants. The results suggest that NH4Cl and inosine affect an early step in germination closely related to the function of an L-alanine receptor.

Alanine↗
PubMed1988

Choice and foraging: the effects of accessibility on acceptability.

Pigeons responded in a successive-encounters choice procedure in which accessibility of the less profitable of two outcomes varied either in terms of probability of encounter or search time to encounter (keeping search time to the more profitable outcome constant). When the less profitable outcome was made more probable its acceptance became more likely. However, when search time to encounter the less profitable outcome was shortened, its acceptance became less likely. Both results are consistent with the delay-reduction hypothesis and with an optimality model developed for application to the successive-encounters choice procedure.

Animals↗
PubMed1987

Apparent endocytosis of fluorescein isothiocyanate-conjugated dextran by Saccharomyces cerevisiae reflects uptake of low molecular weight impurities, not dextran.

Concurrent with Riezman's report (Riezman, H. 1985, Cell. 40:1001-1009) that fluid-phase endocytosis of the small molecule Lucifer yellow occurs in the yeast Saccharomyces cerevisiae, Makarow (Makarow, M. 1985. EMBO [Eur. Mol. Biol. Organ.] J. 4:1861-1866) reported the endocytotic uptake of 70-kD FITC-dextran (FD) and its subsequent compartmentation into the yeast vacuole. Samples of FD synthesized and purified here failed to label yeast vacuoles under conditions that allowed labeling using commercial FD. Chromatography revealed that the commercial FD was heavily contaminated with at least three low molecular weight fluorescent compounds. Dialysis was ineffective for removing the contaminants. After purification (Sephadex G25, ethanol extraction), commercial FD was incapable of labeling vacuoles. Extracts of cells labeled with partially purified FD contained FITC, not FD, based on Sephadex and thin layer chromatography. In either the presence or absence of unlabeled 70-kD dextran, authentic FITC (10 micrograms/ml) was an effective labeling agent for vacuoles. The rapid kinetics (0.28 pmol/min per 10(6) cells at pH 5.5) and the pH dependence of FITC uptake suggest that the mechanism of FITC uptake involves diffusion rather than endocytosis. In view of these results, labeling experiments that use unpurified commercial FD should be interpreted with caution.

Antigens↗
PubMed1984

Stimulation of germination of unactivated Bacillus cereus spores by ammonia.

Inclusion of ammonia in germinant mixtures containing L-alanine and inosine stimulated germination of unactivated Bacillus cereus spores at rates equal to those obtained using heat-activated spores without ammonia. D-Alanine had little effect on germination of heat-activated spores, but severely inhibited germination of unactivated spores in the presence of ammonia. Ammonia did not replace the requirement for either L-alanine or inosine: all three compounds were required for rapid germination. Kinetic analysis suggested that the functions of ammonia and L-alanine were more closely related than the functions of ammonia and inosine. With rate-saturating concentrations of L-alanine and inosine, germination rates showed saturation kinetics for ammonia with a Km for NH4Cl of 5 mM. Comparisons of the effects of salts, amines and pH on germination rates suggested that NH4OH rather than NH+4 was the rate-limiting form of ammonia. In comparisons of various strains of B. cereus, stimulation of germination by ammonia occurred in all cases, although spores of most soil isolates germinated more rapidly than B. cereus T spores in the absence of ammonia.

Alanine↗
PubMed1983

The efficacy of postoperative autotransfusion in patients undergoing cardiac operations.

The efficacy of postoperative autotransfusion in lowering the requirement for banked-blood transfusion was studied in two groups, each having 168 patients, who underwent cardiac operations between April, 1979, and May, 1980. A Sorenson autotransfusion system was available for use in the autotransfusion group, whereas the control group received routine closed mediastinal drainage. Of the autotransfusion group, 81% met the criterion for autotransfusion (mediastinal losses of 450 ml or more during 4 hours), but only 61% of the autotransfusion group actually received autologous blood (mean autotransfusion volume, 399 +/- 25 ml). The patients receiving autologous blood required significantly less banked blood than their matched controls (447 +/- 60 ml and 744 +/- 83 ml, respectively; p less than 0.001). In the subgroup of patients with large mediastinal losses (more than 1,250 ml), this difference was even greater (autotransfusion, 642 ml compared with control, 1,145 ml; p less than 0.01). Postoperative autotransfusion is a simple, safe, and cost-effective method to reduce dependence on banked blood, especially when mediastinal losses are large. Obtaining maximum benefit requires familiarity of staff with the system and use of a consistent protocol.

Blood Transfusion↗
PubMed1982

Propranolol effects on autonomic function in hypertensive men.

Beta blocker antihypertensive effects are incompletely understood, and may involve alterations in the autonomic nervous system. We studied autonomic function in 12 essential hypertensive men during treatment with placebo and chronic oral propranolol. Propranolol reduced blood pressure and heart rate (both p less than 0.01) with an associated increase in baroreflex sensitivity during phenylephrine testing (p less than 0.02), though amyl nitrite-tested baroreflex sensitivity was unchanged; blood pressure decrement did not correlate with baroreflex enhancement. Response to the cold pressor test and the blood pressure decrement to phentolamine alpha blockade were unaltered by propranolol, suggesting unchanged efferent sympathetic function; nor were several biochemical indices of sympathetic nervous activity influenced by propranolol. Propranolol does perturb autonomic function in man, but the perturbations do not correlate with blood pressure decrement; nor are physiologic or biochemical indices of efferent sympathetic activity reduced by propranolol.

Adult↗
PubMed1981

Long-term clonidine effects on autonomic function in essential hypertensive man.

Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 +/- 0.15 mg/day) alone in 13 essential hypertensive men, assessing several biochemical indices of sympathetic function, as well as physiologic parameters, including baroreflex sensitivity, the cold pressor test, and the hypotensive response to alpha adrenergic blockade. Clonidine diminished mean arterial pressure (from 104 +/- 5 to 84 +/- 3 mmHg; p less than 0.01), without associated changes in several biochemical parameters of sympathetic outflow (urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid; all p greater than 0.1). Circulatory baroreflex function was not enhanced by clonidine, during either the amylnitrite test or the phenylephrine test, before or after parasympathetic blockade with atropine. The cold pressor test, an index of efferent sympathetic pressor function, was also unaltered. The enhanced mean arterial pressure response to phentolamine during clonidine therapy (from a fall of 14.8 +/- 4.3 to 39.4 +/- 5.2 mmHg, p less than 0.01), suggested an increase in alpha adrenergic vascular tone, perhaps mediated by clonidine's alpha agonist properties in vascular smooth muscle. The antihypertensive mechanism of longterm low dose clonidine cannot reliably be ascribed either to baroreflex enhancement or to suppression of sympathetic outflow.

Adult↗
PubMed1979

Reduced renovascular resistance by clonidine.

The antihypertensive effect of clonidine has been attributed to acute inhibition of sympathetic outflow from the central nervous system. This conclusion is derived from experiments with single doses of clonidine. The mechanism of the long-term blood pressure-lowering effect of clonidine has been less well characterized. Antihypertensive therapy may alter renal hemodynamics and these changes may ultimately affect systemic blood pressure. We studied the effect of long-term clonidine therapy on intrarenal hemodynamics, the renin-angiotensin system, and selected indices of sympathetic nervous system activity in 13 patients with essential hypertension to further elucidate its action. Long-term clonidine therapy resulted in decreased MAP and RVR associated with the suppression of supine but not upright PRA. RPF, RBF, FF, and WBV did not change. UKA, on index of the the putative vasodilating renal kallikrein-kinin system, was also not changed. Our findings suggest a role for PRA in modulating RVR during long-term clonidine therapy. This was associated with the reduction observed in MAP.

Adult↗