Biomedical subjects

B F Johnson

Publications and source records attributed to B F Johnson.

At least 73 records · Page 4Linked to original sources

PubMed1988

Pharmacokinetic interactions with digoxin.

Numerous pharmacological agents have been shown to produce clinically significant pharmacokinetic interactions with digoxin. Drugs which reduce digoxin absorption include the antacids aluminium hydroxide, magnesium hydroxide and magnesium trisilicate, the antidiarrhoeals kaolin and pectin, the hypocholesterolaemic agent cholestyramine and the chemotoxins cyclophosphamide, vincristine and bleomycin. Certain antibiotics including sulphasalazine, neomycin and aminosalicylic acid reduce digoxin absorption while others, including erythromycin and tetracycline, increase the bioavailability of digoxin in some patients. Capsule preparations of digoxin in solution are less subject to several of the interactions which affect the absorption and bioavailability of digoxin tablets. Various drugs induce alterations in the volume of distribution and clearance of digoxin. Cardiac patients receiving digoxin therapy are particularly prone to interactions with commonly co-administered medications such as the antiarrhythmics quinidine and amiodarone, the calcium channel blockers verapamil and nifedipine, and possibly some vasodilating agents. Studies of digoxin interactions have yielded discrepant results, indicating the need for careful analysis of investigational design before arriving at clinical conclusions.

Digoxin↗

PubMed1987

The effect of dietary fiber on the bioavailability of digoxin in capsules.

Sixteen healthy volunteers were regularly given 0.4 mg of digoxin daily as two capsules with breakfast. After ten days during which breakfast was supplemented with 11 g of bran fiber, steady-state predose mean serum digoxin was lower (0.89 +/- 0.19 versus 0.84 +/- 0.18 ng/mL, P less than .05) and mean 24-hour area under curve determination was lower (30.5 +/- 6.1 versus 28.4 +/- 6.0 ng X hr/mL, P less than .05) than during the control period without bran. Height and time of peak serum digoxin, and 24-hour urinary digoxin were not significantly different. The 6 to 7% reduction in digoxin absorption from capsules is less than that reported from tablets and is probably clinically unimportant.

Adult↗

PubMed1987

The comparative effects of verapamil and a new dihydropyridine calcium channel blocker on digoxin pharmacokinetics.

Conflicting conclusions have been reported about interaction of calcium channel blockers with digoxin. The effects of verapamil (240 mg/day) and a new dihydropyridine calcium channel blocker, isradipine (15 mg/day), on the pharmacokinetics of 1 mg intravenous digoxin were compared. All 24 volunteer subjects were healthy, male, nonobese, and aged 18 to 38 years. Groups of 12 subjects received each oral agent over 15 days, with collections of blood and urine for 72 hours after intravenous digoxin. Significant (P less than 0.05) reduction in nonrenal (7.01 +/- 1.97 to 4.00 +/- 1.86 L/hr) and total clearance (14.1 +/- 2.6 to 11.5 +/- 2.5 L/hr) were induced by verapamil, without change in renal clearance. A near-significant (P less than 0.1) increase in peripheral volume of distribution contributed to prolonged elimination half-life (23.1 +/- 4.4 to 34.3 +/- 9.7 hours). By contrast, isradipine caused only a 9% reduction in volume of distribution. Verapamil causes digoxin accumulation by reducing nonrenal elimination. No evidence of clinically relevant interaction of isradipine with digoxin was seen.

Adolescent↗

PubMed1987

A method for demonstrating subclinical inguinal herniae in patients undergoing peritoneal dialysis: the isotope 'peritoneoscrotogram'.

We report six patients who presented with genital oedema associated with continuous ambulatory peritoneal dialysis (CAPD) who had no clinically detectable inguinal hernia at the time of initial presentation. In the absence of conventional clinical signs of an inguinal hernia, isotope imaging of the pelviscrotal region after introducing technetium-labelled tin colloid through the dialysis tube has proved to be an accurate guide to localisation of the hernia, has avoided unnecessary bilateral explorations, and has facilitated early repair of the hernia, thus allowing reinstitution of CAPD.

Edema↗

PubMed1986

Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model.

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Animals↗

PubMed1986

The influence of pindolol and hydrochlorothiazide on blood pressure, and plasma renin and plasma lipid levels.

After three weeks' administration of placebo, three groups of eight patients with moderate hypertension were randomly assigned to single daily dose, double-blind treatment with either pindolol 15 mg, hydrochlorothiazide 50 mg, or a combination of both for eight weeks. All determinations were made 24 hours after ingestion of a dose. Reductions in supine, sitting, and standing systolic and diastolic blood pressure were greater in patients receiving hydrochlorothiazide than in those administered pindolol; however, the greatest reductions were registered in individuals receiving combination therapy. Mean basal plasma renin activity rose significantly from 0.45 +/- 0.44 to 1.42 +/- 1.31 ng/mL/hr and from 0.67 +/- 0.46 to 1.27 +/- 0.83 ng/mL/hr in patients receiving hydrochlorothiazide and combination therapy, respectively, but there was no change in those administered pindolol. Hydrochlorothiazide and combination therapy increased mean total cholesterol levels from 247 +/- 25 to 263 +/- 37 mg/dL and 198 +/- 36 to 211 +/- 33 mg/dL, respectively, at eight weeks, and both increased mean triglyceride concentrations at two weeks. Pindolol did not show any tendency to alter lipid levels. Pindolol should be given twice daily. At 15 mg daily, it has little or no effect on basal plasma renin activity or plasma lipid levels.

Adult↗

PubMed1986

Variability of steady-state digoxin kinetics during administration of tablets or capsules.

An encapsulated solution of digoxin has been repeatedly shown to have greater bioavailability than tablet forms of the drug. It is predicted that such a preparation would show reduced within- and between-patient variability in absorption, as most studies in normal subjects have shown reduced intersubject variation with the capsule. We tested inter- and intrapatient variability during 4-week periods of dosing with digoxin capsules and tablets in 28 subjects with cardiac disease. In the overall group there were no significant differences between the formulations at steady state in between-patient variability in trough serum digoxin concentrations or 24-hour urinary digoxin excretion. Within-patient variability in urinary digoxin excretion was somewhat lower for the capsules. In a subgroup of six patients who excreted significant amounts of cardioinactive bacterial metabolites (digoxin reduction products [DRP]), the mean (+/- SD) percent urinary DRP excretion was less (p less than 0.05) during capsule (20.5% +/- 15.1%) than tablet (34.4% +/- 10.9%) dosing. Within-patient variability in urinary DRP excretion was much greater after tablets than capsules. Certain subgroups of patients should benefit from the enhanced bioavailability of digoxin capsule preparations.

Absorption↗

PubMed1986

Hemodynamic and metabolic effects of the calcium channel blocking agent nitrendipine.

In an open crossover comparison of propranolol and nitrendipine, 19 patients with hypertension received 40 to 160 mg propranolol and 5 to 20 mg nitrendipine twice a day. Mean (+/- SD) predose supine blood pressure fell from 145/98 +/- 11/7 to 132/88 +/- 12/8 mm Hg with propranolol and to 135/92 +/- 11/9 mm Hg with nitrendipine. Resting heart rate was reduced by propranolol but was unchanged 12 hours after nitrendipine dosing. Neither propranolol nor nitrendipine altered plasma glucose or insulin after oral glucose. Propranolol significantly increased fasting triglyceride levels and reduced high-density lipoprotein cholesterol levels, but nitrendipine induced no change. Propranolol reduced and nitrendipine increased plasma renin activity after exercise. Peak plasma nitrendipine levels were dose proportional and occurred at 1 to 2 hours after dosing, whereas peak blood pressure reductions occurred 4 hours after the last dose of nitrendipine and were associated with mean increases in heart rate. Nitrendipine is almost equivalent in hypotensive effect to propranolol, but nitrendipine increases plasma renin activity after exertion and may produce transient tachycardia. However, nitrendipine does not cause unwanted metabolic effects.

Administration, Oral↗

PubMed1986

The effects of thiazide diuretics upon plasma lipoproteins.

In a double-blind, placebo-controlled, crossover study in 16 hypertensives, 4 weeks of 50 mg hydrochlorothiazide twice daily, caused significant elevations in total plasma cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, very low density lipoprotein (VLDL)-cholesterol and triglycerides. Significant elevations in fasting plasma glucose and in plasma insulin were observed, but no correlation between individual lipid elevations and either glucose or insulin elevations was apparent. The metabolic effects developed within 2 weeks, and dissipated within 4 weeks. Changes induced within 4 weeks of treatment with hydrochlorothiazide were unaltered at 6 months. Hydrochlorothiazide induces elevation of all lipoprotein cholesterol fractions and VLDL-triglyceride. However, as the important ratio between LDL- and HDL-cholesterol is unchanged, coronary risk may be unchanged.

Adult↗

PubMed1986

Salivary concentrations of pirmenol as a possible cause of unpleasant taste.

Salivary concentrations of the anti-arrhythmic, pirmenol, were compared with plasma concentrations in six patients. Group mean salivary values tended to be higher despite high plasma protein binding, suggesting the possibility of an active transport process. The observed salivary concentrations are reasonably close to those detectable in healthy volunteers as tasting unpleasant.

Adult↗

PubMed1986

Long-term stability study of histamine in sterile bronchoprovocation solutions.

The long-term stability of histamine in sterile bronchoprovocation solutions stored under different conditions was studied. Histamine solutions (2 and 8 mg/mL) were stored in specially adapted translucent and black plastic bottles and kept in a cool place (12 degrees C) and exposed to fluorescent light (500 foot-candles intensity). Multiple aliquots of each concentration were also stored at -20 degrees C in 12 X 75 mm sterile polypropylene tubes with snap caps and covered with aluminum foil. The content of histamine in the stored samples was determined by a stability-indicating colorimetric assay. The histamine solutions were stable for up to eight months at 12 degrees C when stored in either of the specially adapted translucent or black plastic bottles, irrespective of normal long-term exposure to fluorescent light. No important changes were observed in the histamine concentration when these solutions were stored at -20 degrees C in polypropylene tubes for up to a year. Histamine solutions used in bronchoprovocation tests can be stored in plastic bottles in a cool place or in the refrigerator. It is not necessary to protect these solutions from normal long-term exposures to fluorescent light to ensure clinically acceptable stability.

Bronchial Provocation Tests↗

PubMed1985

Stability of stored histamine diphosphate solutions. Clinically useful information.

Histamine bronchoprovocation challenge has been shown to be extremely safe and useful as both a clinical diagnostic test and as a research tool in the study of bronchial asthma. Despite its widespread usage, information on the stability of histamine diphosphate (HDP) solutions has been lacking. We therefore studied the stability of HDP solutions as a function of time, concentration, fluorescent light exposure, and sterility. Our results indicated that HDP solutions between 2.76 and 22.10 mg/ml (histamine base, 1 to 8 mg/ml) show no evidence of degradation over a 4-month period when kept at 12 degrees C, unless gas sterilization techniques were used in preparing the solutions bacterial contamination was frequent, and at lower concentrations (i.e., between 0.08 and 0.28 mg/ml) HDP solutions that became contaminated with bacteria showed complete degradation within 9 to 11 wk of their preparation.

Bacteria↗

PubMed1985

Simple stability-indicating assay for histamine solutions.

A chemical stability-indicating assay for the routine analysis of histamine in isotonic-phosphate buffer solutions was developed and evaluated. A quantitative colorimetric assay was developed by adapting the Pauly reaction specific for the imidazole group for the determination of histamine in buffer solutions. Stock solutions of histamine diphosphate 1 mg/mL were diluted with isotonic phosphate buffer to produce standards for an imidazole-group assay and for the USP assay method based on the Folin reaction of free amino groups. The specificity of the assays was evaluated by subjecting samples to ultraviolet irradiation and heat for various time periods and then analyzing for histamine content. Both of the colorimetric assays provided reproducible linear calibration curves passing through the origin for histamine diphosphate concentrations. For the Pauly-reaction assay, the average coefficients of variation between and within runs were 0.5% and 0.1%, respectively. The assay had recoveries of 100.6% and 100.8% at 8 and 25 micrograms/mL of histamine diphosphate concentrations, respectively, and a sensitivity of 3 micrograms/mL. Based on the results of the Pauly-reaction assay, irradiation caused decreases in the apparent concentrations as large as 69.2% depending on the duration of the irradiation and distance from the light source. When the histamine diphosphate solutions were stored in the dark at 60 degrees C for five days, a decrease of only 6.3% occurred. Based on the results of the Folin-reaction assay, irradiation caused increases in the apparent concentrations as large as 50.6%. The Pauly colorimetric assay based on the imidazole group appears to be more appropriate for histamine solutions than the amino-group assay based on the Folin reaction.

Amines↗

PubMed1984

Comparative effects of propranolol and prazosin upon serum lipids in thiazide- treated hypertensive patients.

Earlier reported thiazide-induced changes in serum lipid concentrations were confirmed with increased triglyceride and total cholesterol levels. However, lipoprotein cholesterol ratios were unchanged. Propranolol caused further increases in triglyceride and very low-density lipoprotein cholesterol, and lowered high-density lipoprotein cholesterol and the high-density lipoprotein:total cholesterol ratio. With the addition of prazosin to the polythiazide regimen, there was a significant increase in serum high-density lipoprotein cholesterol when compared with the placebo.

Adult↗

PubMed1984

Two-dimensional electrophoretic analysis of the regulation of SOS proteins in three ssb mutants.

A previously undescribed mutation in the ssb gene, which codes for a major single strand DNA binding protein essential for DNA replication, was mapped on the Escherichia coli chromosome. Three ssb mutants were analyzed under parallel physiological conditions for the induction of SOS proteins (products of recA, uvrA, and an unknown gene), the production of mutants, the induction of lambda prophage, and sensitivity to DNA damaging agents. Two-dimensional electrophoretic techniques were used to quantitate changes in the rate of synthesis of proteins. The previously unpublished position of the uvrA gene-product in the two-dimensional matrix of E. coli proteins was described. These ssb strains exhibited varying sensitivities to ultraviolet irradiation and methylmethane sulfonate that correlated with the rate of constitutive synthesis of SOS proteins, spontaneous commitment to virulent growth of lambda lysogens, and elevation of endogenous mutation rates.

Bacterial Proteins↗

PubMed1984

Effect of metoclopramide on digoxin absorption from tablets and capsules.

The effect of metoclopramide, a drug that increases gut motility, on the consistency of digoxin absorption was examined in 16 healthy men. Each received the following four single-dose digoxin treatments in complete crossover fashion: two 0.25-mg digoxin tablets, alone, and two 0.2-mg digoxin capsules with metoclopramide. Mean serum AUCs over 24 hr (AUC-24) and cumulative urinary digoxin excretion over 48 hr (CUE-48) were of the same order for the tablets and capsules alone treatments. Metoclopramide reduced the mean AUC-24 for tablets from 12.26 +/- 2.70 to 9.38 +/- 3.78 ng X hr/ml (P less than 0.001) and the CUE-48 from 119.0 +/- 22.4 to 97.6 +/- 22.2 micrograms (P less than 0.01). There were no significant differences in mean AUC-24 (12.94 +/- 3.16 and 13.45 +/- 2.33 ng X hr/ml) and mean CUE-48 (117.8 +/- 23.4 and 109.7 +/- 25.0 micrograms) when capsules alone were compared to capsules with metoclopramide. Metoclopramide reduced the time to reach peak concentration for both digoxin dosage forms. The effect of metoclopramide on digoxin absorption is minimized by administration of digoxin in capsules.

Absorption↗

PubMed1984

Relationship Between Substrate Concentration and Fermentation Product Ratios in Clostridium thermocellum Cultures.

Growth of Clostridium thermocellum in batch cultures was studied over a broad range of cellobiose concentrations. Cultures displayed important differences in their substrate metabolism as determined by the end product yields. Bacterial growth was severely limited when the initial cellobiose concentration was 0.2 (wt/vol), was maximal at substrate concentrations between 0.5 and 2.0%, and did not occur at 5.0% cellobiose. Ethanol accumulated maximally (38.3 mumol/10 cells) in cultures with an initial cellobiose concentration of 0.8%, whereas cultures in 2.0% cellobiose accumulated only 17.3 mumol, and substrate-limited cultures (0.2% cellobiose) accumulated little, if any, ethanol beyond that initially detected (8.3 mumol/10 cells). In a medium with 0.8% cellobiose, ethanol was produced at a constant rate of approximately 1.1 mumol/10 cells per h from late-logarithmic phase (16 h) of growth well into stationary phase (44 h). When ethanol was added exogenously at levels more than twice the maximum produced by the cultures themselves (0.5% [vol/vol]), neither the extent of growth (maximum Klett units, 150) nor the amounts of ethanol produced ( approximately 0.17%) by the culture was affected. The ratio of ethanol to acetate was highest (2.8) when cells were grown in 0.8% cellobiose and lowest (1.2) when cells were grown in 0.2% cellobiose.

Journal Article↗

PubMed1984

A radioimmunoassay for digoxin in human urine.

We report a digoxin radioimmunoassay in human urine employing commercially available reagents. The calibration curve has a mean correlation coefficient of -0.994 and is linear up to 16.0 micrograms/l. The average coefficients of variation between and within the runs are 3.6% and 3.5% respectively. The assay has a recovery of 101.4% and 98.9% at low and high levels of digoxin excretion respectively. Dihydrodigoxin at concentrations of 4, 8 and 16 micrograms/l has relative cross reactivities of 12.0%, 7.7% and 4.8% respectively. The assay was applied to compare within-patient and between-patient variability during treatments with Lanoxin and Lanoxicaps at steady-state. Precision, sensitivity, broad range linearity, convenience of commercially available reagents, insignificant cross reactivity of dihydrodigoxin with the digoxin antibody complex and urinary digoxin excretory data at different dilutions validate our assay for routine monitoring of urinary digoxin.

Biological Availability↗