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Biomedical subjects

K L Massey

Publications and source records attributed to K L Massey.

At least 19 recordsLinked to original sources
PubMed1990

Effect of oxygen free radicals, hypoxia and pH on the release of liver lysosomal enzymes.

We investigated the effect of acidic environment, hypoxia and oxygen free radicals on the release of beta-glucuronidase from rat liver lysosomes. A lysosomal enriched fraction from the homogenate of rat liver was prepared, using differential centrifugation technique. Exogenous oxygen free radicals were generated using xanthine-xanthine oxidase system. The release of beta-glucuronidase activity was measured from the lysosomes. The lysosomal fraction was exposed to various pH (8.0, 7.4, 6.5, 6.0, 5.5) and pO2 (454, 172, 96, 57,34 mm Hg) separately or to a combination of low pH (5.5, 6.5) and low pO2 (34, 57 mm Hg). The changes in pH or pO2 separately did not cause any increase in the release of beta-glucuronidase activity. The presence of oxygen free radicals at each pH or pO2 resulted in about a 3-fold increase in the release of beta-glucuronidase. A combination of very low pO2 and pH (pO2 (mm Hg)/pH; 34/5.5, 34/6.5) resulted in an increased release of beta-glucuronidase from lysosomes. Oxygen free radicals in the presence of both low pO2 and pH resulted in a further increase in the release of beta-glucuronidase. These data indicate that oxygen free radicals and not the alterations in pH and/or pO2 are primarily responsible for the disruption of lysosomes.

Animals↗
PubMed1990

A modification of the urine osmolal gap: an improved method for estimating urine ammonium.

A modification of the urine osmolal gap was evaluated as an estimate of urine [NH4+]. We proposed that: Urine [NH4+] = Urine osmolality - [2(Na+ + K+) + urea + glucose]/2 Spot urine samples were collected from normal volunteers and from individuals with ketonuria; the modified urine osmolal gap as well as two other previously described estimates of urine [NH4+] were compared with measured urine [NH4+]. There was a significant positive linear correlation between the urine [NH4+] and the modified urine osmolal gap in normal volunteers (r = 0.81; p less than 0.01) and in individuals with ketonuria (r = 0.93; p less than 0.001). The originally described urine osmolal gap greatly overestimated the urine [NH4+] but also showed a significant correlation. The urine anion gap was not a valid estimate of urine [NH4+] within the range of values measured in our subjects. The modified urine osmolal gap is an improvement over previously described estimates of urine [NH4+] and can be used as a single calculation in place of the other two.

Acid-Base Equilibrium↗
PubMed1989

Symptom awareness and blood glucose estimation in diabetic adults.

Self-regulation of diabetes depends in part on common-sense models of symptoms and blood glucose fluctuations. Symptom perception and subjective estimation of blood glucose were studied in 52 adult, difficult-to-control, non-insulin-dependent diabetics using a structured interview and laboratory blood-glucose measurement. Most patients believed they could detect hyperglycemia. Symptoms linked by patients to hyperglycemic and hypoglycemic episodes did overlap with symptoms traditionally associated with those states. Some patients may experience dysphoria during glycemic swings to which multiple symptom labels are applicable, although prominent exceptions and idiosyncratic symptoms were evident. Estimation of current blood glucose using an ordinal scale suggested some capacity for discriminating blood glucose levels. Numerical estimates of Chemstrip values were correlated with actual values, but far too inaccurately for purposes of self-regulation. Research is needed to clarify whether subjective symptom perception and blood glucose estimation helps or hinders self-regulation of diabetes.

Awareness↗
PubMed1989

Increased production of oxygen free radicals by polymorphonuclear leukocytes in heart failure due to aortic stenosis.

Oxygen free radicals have been linked to a wide variety of cellular damage in biological systems. Polymorphonuclear (PMN) leukocytes stimulation is one of the known sources for oxygen free radicals. It has been suggested that oxygen free radicals depress the excitation-contraction coupling in cardiac muscle. It is possible that a decrease in the myocardial contractility in heart failure might be due to an increased oxygen-free-radical-producing activity of PMN leukocytes. The authors studied, therefore, the release of oxygen free radicals, as measured by luminol-dependent chemiluminescence activity, from the PMN leukocytes in dogs with heart failure due to aortic stenosis. Hemodynamics and phagocytic activity of PMN leukocytes were studied in 6 control dogs and 6 dogs with aortic stenosis of six to nine months' duration. There was a significant decrease in the index of myocardial contractility and an increase in the left ventricular end-diastolic pressure in dogs with aortic stenosis, suggesting left ventricular failure in these dogs. Although there was a tendency for a decrease in the cardiac index in dogs with aortic stenosis, the decrease was not significant. Phagocytic activity of PMN leukocytes in blood was studied in control dogs and dogs with aortic stenosis. Phagocytosis was initiated by addition of opsonized zymosan and chemiluminescence was monitored by use of a luminometer. The peak chemiluminescence activity of the PMN leukocytes in blood of dogs with heart failure was about threefold greater than that in the blood from control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Duration of effect of gallopamil, a calcium channel blocker, on methacholine-induced bronchoconstriction.

We previously demonstrated a modest but significant protective effect of inhaled gallopamil (D600), the methoxy derivative of verapamil, against methacholine-induced bronchoconstriction; however, the duration of the protective effect of this and other calcium channel blockers is unknown. We therefore evaluated the duration of this protective effect in 15 asthmatic subjects in a prospective, placebo-controlled trial. Methacholine challenges (Cockcroft method) were performed 2 hours before and 30 minutes after the administration of placebo, and 1 mg and 10 mg of inhaled gallopamil. Gallopamil did not alter resting airway caliber, but significantly increased the concentration of methacholine required to decrease the FEV1 20% 30 minutes after the dose. Results with both the 10-mg and 1-mg doses were significantly different from placebo, but not from each other. The duration of this protective effect was transient in the group as a whole; the mean drug activity ratios were not significantly different with this sample 2.5 hours after the dose. Thus the short duration of effect limits the potential clinical usefulness of gallopamil in suppressing the signs and symptoms of chronic asthma.

Adolescent↗
PubMed1988

Oxygen free radicals induced release of lysosomal enzymes in vitro.

The effect of oxygen free radicals, generated by xanthine and xanthine oxidase, was studied on the release of lysosomal hydrolase from rat liver lysosomes in vitro. A lysosomal enriched subcellular fraction was prepared, using differential centrifugation technique, from the homogenate of rat liver. The biochemical purity of the lysosomal fraction was established by using the markers of different cellular organelles. Oxygen free radicals were generated in vitro by the addition of xanthine and xanthine oxidase. The release of lysosomal hydrolase (beta-glucuronidase) from the lysosomal fraction was measured. There was a 3 to 4 fold increase in the release of beta-glucuronidase activity in the presence of xanthine and xanthine oxidase when compared to that in the absence of xanthine and xanthine oxidase. In the presence of superoxide dismutase (SOD), a scavenger of oxygen free radicals, the xanthine and xanthine oxidase system was unable to induce the release of beta-glucuronidase activity from the lysosomes. Sonication (2 bursts for 15 sec each) and Lubrol (2 mg/10 mg lysosomal protein) treatment, which are known to cause membrane disruption, also induced the release of beta-glucuronidase from lysosomal fraction. This release of beta-glucuronidase by sonication and lubrol treatment was not prevented by SOD. These data indicate that lysosomal disruption is a consequence of oxygen free radicals, generated by xanthine and xanthine oxidase.

Animals↗
PubMed1988

Duration of protection of calcium channel blockers against exercise-induced bronchospasm: comparison of oral diltiazem and inhaled gallopamil.

The present study was conducted to determine the duration of the positive effect of oral diltiazem and inhaled gallopamil in mild asthmatic volunteers, ages 18-37 years, with a history of exercise-induced asthma and a 25-56% decrease in FEV1 after a standardized exercise challenge. Oral diltiazem 120 mg, inhaled gallopamil 10 mg, and placebo were administered in a double blind, randomized, crossover manner on different days 48 h apart. Diltiazem was administered 90 min and gallopamil 30 min before the first exercise challenge. Challenges were then repeated 3 and 6 h later. Neither diltiazem nor gallopamil significantly altered baseline FVC, FEV1, or FEF25-75. The mean maximum decrease in FEV1 after the first challenge was 16.8% after gallopamil, 25.2% after diltiazem and 30.1% after placebo. The mean post-exercise decrease in FEV1 after gallopamil was significantly smaller than after placebo. There were no significant differences in the post-exercise decreases in FEV1 between the three treatment regimens 3 and 6 h later. Thus, inhaled gallopamil provided significant protection against exercise-induced bronchospasm, but the beneficial effect was modest and short in duration.

Administration, Inhalation↗
PubMed1988

Dose response of inhaled gallopamil (D600), a calcium channel blocker, in attenuating airway reactivity to methacholine and exercise.

To determine if there is a dose-response relationship for calcium channel blockers in preventing experimentally induced bronchoconstriction, we evaluated the effects of inhaled gallopamil (D600), a potent methoxy derivative of verapamil, on airway reactivity to methacholine and exercise in volunteers with mild asthma. Methacholine challenges were completed by 11 subjects 2 hours before and 20 minutes after placebo, and 1, 2, 5, 10, and 20 mg of inhaled gallopamil administered in a single-blind, randomized manner on different days. Gallopamil did not significantly alter FVC, FEV1, or forced expiratory flow rate between 25% and 75% of FVC, but increased the dose of methacholine required to produce a 20% decrease in FEV1 from baseline (p less than 0.0001). The mean +/- SEM fold increase in the dose of methacholine required to produce a 20% decrease in FEV1 from baseline was 1.0 +/- 0.1 after placebo, 2.4 +/- 0.2 after 1 mg, 2.2 +/- 0.2 after 2 mg, 2.5 +/- 0.2 after 5 mg, 2.5 +/- 0.3 after 10 mg, and 2.3 +/- 0.2 after 20 mg. Thirty minutes before a standardized exercise challenge, 10 subjects inhaled 1 and 10 mg of gallopamil or placebo in a randomized, double-blind, crossover manner. The mean +/- SEM maximum decrease in FEV1 after exercise was 25.1 +/- 5% after 10 mg of gallopamil (p less than 0.01), 34.4 +/- 5% after 1 mg (p greater than 0.05), and 39.0 +/- 6% after placebo. We conclude that inhaled gallopamil only modestly alters airway reactivity to methacholine; increasing the dose greater than 1 mg did not provide greater benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Regulation of carnosine metabolism: the subcellular localization of carnosinase in liver.

We studied the subcellular localization of carnosinase (EC 3.4.13.3) in rat liver. The liver homogenate was fractionated by differential centrifugation into a nuclear (N), a mitochondrial (M), a lysosomal (L), a microsomal (P) and a soluble (S) fraction. The purity of different subcellular fractions was established by using different markers. The carnosinase activity in different fractions was measured by fluorometric determination of L-histidine produced using carnosine as a substrate. The intracellular distribution of carnosinase was very similar to that of lactate dehydrogenase with the highest relative specific activity of enzyme being observed in the soluble fraction. These results indicate that carnosinase enzyme is primarily located in the soluble (cytoplasmic) fraction of rat liver.

Animals↗
PubMed1988

Relative efficacy of phenytoin and phenobarbital for the prevention of theophylline-induced seizures in mice.

We evaluated the efficacy of pretreatment with phenytoin and phenobarbital to prevent seizures in mice given convulsive doses of theophylline. The control LD50 for theophylline was determined in 48 mice by intraperitoneal injections of increasing doses without anticonvulsant treatment. Anticonvulsant effects were determined in 105 additional mice pretreated with either phenytoin 30 mg/kg (n = 35), phenobarbital 35 mg/kg (n = 30), or phenobarbital 60 mg/kg (n = 40) one hour before theophylline administration. The theophylline LD50 (95% confidence interval) was 239 mg/kg (range, 229 to 248 mg/kg) for controls, 204 mg/kg (range, 194 to 214 mg/kg) for phenytoin, 305 mg/kg (range, 288 to 323 mg/kg) for low-dose phenobarbital, and 319 mg/kg (range, 307 to 331 mg/kg) for high-dose phenobarbital. Each LD50 differed significantly from control (P less than .05). The phenobarbital groups were significantly different from phenytoin (P less than .05) but not from each other. Theophylline serum concentrations were not significantly different among groups after adjustment for different doses. The mean +/- SEM time to seizure in minutes after adjustment for theophylline dose was 23.5 +/- 4.0 minutes for controls, 5.7 +/- 7.5 minutes for phenytoin, 44.1 +/- 7.1 minutes for low-dose phenobarbital, and 63.7 +/- 6.5 minutes for high-dose phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Evaluation and assessment of high sensitivity thyrotropin methods as an index for thyroid function.

We report the evaluation of four new commercially available sensitive assay kits for determination of thyrotropin (TSH) and their clinical utility in normal subjects and patients with thyroidal and non-thyroidal illnesses. The sensitivity for the reliable detection of serum TSH by these methods ranged from 0.1-0.4 mU/L and their decreasing order was : NML greater than Serono greater than Abbott EIA greater than Hybritech. The coefficient of variation ranged from 2.0-5.8% for intra-assay and 2.3-8.6% for interassay at different concentration levels. Patients studied (n = 130) were assigned into four groups on the basis of the serum thyroxine value and their clinical findings. In total, there were 17 discrepancies (five with Hybritech, three with NML, five with Abbott EIA, and four with Serono) in making the correct diagnosis using these sensitive TSH methods as a single diagnostic test. These discrepancies were mainly in the same patients who were clinically euthyroid but had subnormal TSH values. There were no discrepancies in making the correct diagnosis for patients with hyperthyroidism or hypothyroidism using these sensitive TSH methods. Our observations indicate that the sensitive TSH methods are reliable in measuring subnormal levels and may be used to detect hyperthyroidism without affecting in any way their value in detecting hypothyroidism.

Adolescent↗
PubMed1987

Calcium antagonists in the management of asthma: breakthrough or ballyhoo?

Research demonstrating the importance of intracellular calcium regulation in each of the pathophysiologic events of asthma has lead to speculation that calcium antagonists may be beneficial in the treatment of reactive airways disease. A plethora of data has been generated on the effects of verapamil, diltiazem, nifedipine, and several investigational agents on experimentally induced asthma, indicating that none of these agents significantly affects resting bronchomotor tone, and their efficacy in preventing bronchospasm is a function of the drug, dose, route of administration and method of bronchoprovocation. Most studies have demonstrated calcium antagonists have only modest and highly variable effects on airway smooth muscle contraction. Additional studies are needed to define the effects on the inflammatory component of airways obstruction, steroid requirements in steroid-dependent patients, and on the alteration of the pharmacodynamics of other agents used for the management of chronic asthma.

Asthma↗
PubMed1986

Identification of children for whom routine monitoring of aminoglycoside serum concentrations is not cost effective.

On the basis of our clinical impression that aminoglycoside serum concentration measurements did not result in dosage changes in many children with normal renal function, data collected during pharmacokinetic consultations were evaluated to identify pediatric patients for whom routine serum concentration monitoring would not be cost effective. The frequency of peak or trough concentrations outside the desired ranges was related to age and duration of therapy in 88 children with normal renal function who were given recommended doses of gentamicin or tobramycin. Trough concentrations were outside the target range (greater than 2 micrograms/ml) in five of 26 patients who had received more than 10 days of therapy or were older than 18 years of age. In contrast, troughs were less than 2 micrograms/ml and did not significantly increase over the course of therapy in all patients who were younger than 18 years of age and had received less than 10 days of therapy. This latter group represented 36% of all aminoglycoside pharmacokinetic consultation requests to our service. In addition, when infusion technique and sample time were meticulously controlled, peak concentrations were greater than or equal to 4 micrograms/ml in all patients who had received a dose of approximately 2.5 mg/kg. We conclude that routine peak and trough measurements are unnecessary in patients between 3 months and 18 years of age unless duration of therapy extends beyond 10 days, renal function is impaired, there is a clinical need for higher doses or shorter dosing intervals, or a potential nephrotoxin has been administered in the previous 3 months.

Adolescent↗
PubMed1986

Current concepts in clinical therapeutics: asthma.

The epidemiology, etiology, pathophysiology, diagnosis, and treatment of asthma are reviewed, and the major drugs used in treating asthma are discussed in depth. In terms of morbidity, mortality, and economic impact, asthma is a serious disease. About nine million Americans suffer from it, and in a recent year nearly 2000 people died from it. The underlying mechanism of asthma appears to be a hyperreactivity of the airways to certain stimuli, including environmental irritants, exercise, and psychological factors. The symptoms of asthma are caused by spasm of airway smooth muscle, increased mucus secretion, and inflammation. Asthma may be classified as intermittent (patients with extended symptom-free periods) or chronic (patients with frequent exacerbations). Diagnosis of asthma relies heavily on a comprehensive patient history confirmed with objective physiologic data. Acute or intermittent asthma should be treated first with inhaled beta 2 agonists such as albuterol or terbutaline. Corticosteroids should be started if the response to the beta 2 agonists is inadequate, and theophylline may be used while waiting for the steroids to exert an effect. Adequate hydration, correction of metabolic acidosis, and oxygen are essential supportive measures. Theophylline appears to be the best noncorticosteroid for chronic asthma, although cromolyn is an acceptable alternative. Sympathomimetic bronchodilator therapy and corticosteroids may be needed adjunctively. Immunotherapy is indicated in patients with chronic asthma caused by specific allergens and poorly controlled on theophylline or cromolyn. Asthma is best managed using multiple pharmacologic agents in response to specific events and symptoms, making optimal therapy difficult to achieve and sometimes difficult to define.

Adrenal Cortex Hormones↗