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Biomedical subjects

T Taylor

Publications and source records attributed to T Taylor.

At least 163 records · Page 9Linked to original sources
PubMed1984

The influence of food and repeated dosing on the bioavailability of indomethacin from a multiple-units controlled-release formulation.

A concomitant meal did not affect the extent of bioavailability of indomethacin from a multiple-units controlled-release capsule formulation containing enteric-coated pellets, but the presence of food delayed absorption. When a capsule containing 75 mg indomethacin was administered after a 12 h fast, the mean peak drug concentrations in plasma of 2.7 micrograms/ml +/- 0.8 SD occurred at a mean time of 4.2 h (range 2-6 h). When this dose was administered with a substantial breakfast, the mean of the peak plasma concentration of 2.2 micrograms/ml +/- 1.0 SD occurred at 6.4 h (range 5-12 h). Secondary peak plasma drug concentrations, occurring at approximately 14 h after dosing, were more prominent and the times to reach the second peak more variable when the capsules were administered with food. Drug bioavailability after co-administration with food was 91% of that following administration after fasting. When the controlled-release capsule was administered during 3 days in a b.i.d. dosage regimen, drug bioavailability was 103% of that from a standard capsule administered q.i.d. The mean peak level after administration of the last dose of 50 mg as controlled-release capsules was 2.5 micrograms/ml +/- 1.1 SD and the means of peak levels after the penultimate and last doses of 25 mg as standard capsules were 2.0 micrograms/ml +/- 0.3 SD and 2.1 micrograms/ml +/- 0.7 SD, respectively. The controlled-release capsule formulation was a reliable and reproducible source of indomethacin when administered as repeated doses or with food.

Adult↗
PubMed1984

[Bioavailability of isosorbide-5-mononitrate from delayed-action formulations].

The relative bioavailability of isosorbide-5-mononitrate (IS-5-MN) has been determined after a 3-day period of dosing with 20 mg in standard-release reference tablets and sustained-release capsules at 12-h intervals, 40 mg in sustained-release capsules (Olicard 40 retard) at 24-h intervals and after single oral dose of 60 mg sustained-release capsules (Olicard 60 retard), in a cross-over study with 12 human subjects. Accumulation factors of 1.1-fold or 1.2-fold occurred during administration of 20 mg in standard- or sustained-release tablets and capsules respectively at 12-h intervals, and negligible accumulation of drug occurred after administration of 40 mg in sustained-release capsules at 24-h intervals or was calculated by the superposition principle to occur after doses of 60 mg in sustained-release capsules at 24-h intervals. The mean extent of bioavailability of IS-5-MN from the 20 mg, 40 mg and 60 mg sustained-release capsules was 79%, 67% and 70% respectively, of that from the standard-release reference tablets. The posterior probability that the bioavailability of IS-5-MN was included within the limits 60%-90% of the reference tablets was 97%, 86% and 95% for the 20 mg, 40 mg and 60 mg sustained-release capsules respectively. Means of peak plasma levels of IS-5-MN after administration of the sustained-released capsules were linearly related to the doses administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Availability↗
PubMed1983

Pancreatic structure and function in the immature reserpinized rat.

Immature rats were reserpinized to determine whether the model used for adults may be suitable for the study of pancreatic exocrine insufficiency seen in infants with cystic fibrosis. Rats were reserpinized by injections either into pregnant dams or into newborn rats. The dose of reserpine used by others was lethal to immature rats, so lower doses were used. Pancreas from 1-day-old fetal-treated pups was hypoplastic, but concentration of chymotrypsinogen was elevated. At age 7 days hyperplasia was seen. When rats were reserpinized as neonates, hypoplasia and decrease in all parameters measured was observed at age 7 days. Progressive recovery occurred during the following 2 weeks in both groups. Electron microscopic study of the fetal-treated 24-hr-old pancreas revealed evidence of acinar cell degeneration with the presence of abnormal zymogen granules. At age 7 days the pancreas from neonatal-treated rat pups appeared to have a reduced number of granules. At ages 14 and 21 days the pancreas was similar to that seen at age 7 days except that the granules were larger and some acinar lumina were filled with a finely granular, homogeneously dense material. It is concluded that prenatal and neonatal reserpinization of rats induces changes in pancreas similar to those found in cystic fibrosis.

Amylases↗
PubMed1983

The percutaneous absorption and excretion of promestriene (3-propoxy-17 beta-methoxy-1,3,5(10)-estratriene) in rats and humans.

The percutaneous absorption of 3H-promestriene (an antiseborrhoeic agent; 3-propoxy-17 beta-methoxy-1,3,5(10)-estratriene) was studied in rats and human subjects. Extensive and continual absorption of the tritium label (about 50% dose in 3 days) occurred in rats when the treated area of skin (ca. 30 micrograms/cm2) was occluded; when unabsorbed material was washed off after 6 h, a substantial proportion of the applied 3H (about 25% dose) had been absorbed to be excreted later. In contrast, less than 1% of the 3H applied to the skin of human volunteers (0.1-0.5 mg/cm2) was absorbed within 6 h and subsequently excreted. In rats, tissue concentrations of 3H were greatest in the liver, adrenals and ovaries.

Absorption↗
PubMed1983

The metabolic fate of the anti-androgenic agent, oxendolone, in man.

After intramuscular administration of 16 beta-ethyl-17 beta-hydroxy-4-4-[4-14C]estren-3-one (14C-oxendolone; 300 mg) to 3 human subjects, excretion of 14C was very slow and incomplete despite a 20-day sample collection period. During this time, means of 37% and 21% of the administered 14C were recovered in urine and faeces, respectively, and if excretion continued at the same rate, approximately 90% of the administered 14C would have been excreted during 5-12 weeks. Peak plasma 14C concentrations were reached at 3-6 days after dosing, when they represented 0.2-1.1 micrograms equiv./ml, and declined very slowly thereafter with a half-life of 5.0-6.6 days. Concentrations of unconjugated drug-related steroids circulating in plasma never exceeded about 0.1 microgram/ml. Mass spectroscopic analysis of isolated urinary and faecal metabolites indicated that the principal routes of biotransformation of oxendolone in man are similar to those of the endogenous androgens-namely, reduction of the 4,5-double bond, further reduction of the saturated 3-ketone to the 3 alpha-hydroxysteroid, and oxidation of the 17 beta-alcohol to the corresponding ketone, followed by conjugation, mainly with glucuronic acid, and excretion in the urine and bile.

Adult↗
PubMed1983

The Winnecott "set situation". A useful tool for the pediatrician.

D.W. Winnecott devised a short, simple test which he used to evaluate normal infants. In this study, we compared 9-month-old infants' behaviors elicited during the Winnecott Test (WSS), both with historical data and with their behavior during a structured separation from their mothers. We found significant correlations between the WSS, the structured separation, and historical data. This simple test can provide the practitioner with invaluable information regarding the infant, his temperamental style, and his relationship with others.

Anxiety, Separation↗
PubMed1983

beta-endorphin suppresses adrenocorticotropin and cortisol levels in normal human subjects.

To determine the effect of beta-endorphin on the pituitary-adrenal axis, human synthetic beta-endorphin was infused iv in 10 normal human subjects. Either beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg . min, each dose for 30 min) or a control (sham) infusion of 5% dextrose water was administered in a blind fashion in the same subjects on 2 successive days. Plasma ACTH and cortisol and serum human GH and PRL levels were measured 30 min before and then every 30 min for 210 min during and after both the beta-endorphin and control infusions. In all subjects, cortisol levels decreased below the basal level in response to the infusion of beta-endorphin. The threshold dose was 1.0 micrograms/kg . min, with the mean control cortisol level (12 +/- 2 micrograms/dl) declining significantly to 7 +/- 1 micrograms/dl (1.0 micrograms/kg . min) and 6 +/- 1 micrograms/dl (3.0 micrograms/kg . min; P less than 0.01). ACTH levels also were significantly lower than the control value (48 +/- 6 pg/ml) at the 1.0 microgram/kg . min dose (32 +/- 4 pg/ml; P less than 0.05). The decline in ACTH and cortisol levels was also significantly different from levels obtained during the control infusions (P = 0.001 and P = 0.01, respectively). The results are consistent with short feedback loop inhibition of pituitary ACTH release or suppression of hypothalamic corticotropin-releasing factor release by beta-endorphin.

Adrenocorticotropic Hormone↗
PubMed1983

Symptomatic hypotension following the clonidine suppression test for pheochromocytoma.

A 42-year-old man with generalized atherosclerosis underwent surgery of the left carotid artery with eventual placement of a Dacron graft bypassing the left carotid sinus. Subsequently, symptoms suggestive of pheochromocytoma developed, and 24-hour urine catecholamine levels were elevated. Clonidine testing resulted in suppression of plasma norepinephrine levels but was complicated by severe hypotension and a transient ischemic attack. Baroreceptor dysfunction may have been involved. Caution is advised and recommendations are offered for future usage of the clonidine suppression test.

Adrenal Gland Neoplasms↗
PubMed1983

Bioavailability of isosorbide dinitrate and its two mononitrate metabolites from sustained-release formulations.

Plasma concentrations and bioavailability of isosorbide dinitrate (ISDN) and its active metabolites isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN) from two sustained-release formulations and one standard-release formulation of isosorbide dinitrate were compared. Means of peak drug concentrations of ISDN, 2-ISMN, and 5-ISMN after administration of the 20-mg sustained-release formulation were 5.5, 24.4, and 129.1 ng/ml, respectively, at 3.1, 4.2, and 4.5 h; after the 40-mg sustained-release formulation, they were 10.9, 44.0, and 214.5 ng/ml, respectively, at 4.2, 6.3, and 6.7 h; and after the 20-mg standard formulation, they were 19.1, 34.7, and 159.2 ng/ml, respectively, at 0.5, 1.0, and 1.5 h. As might be expected, peak concentrations and their times of occurrence were statistically significantly different when results from the sustained-release formulation were compared to those from the standard formulation. Plasma drug concentrations were detectable for longer after administration of the sustained-release formulations. The extent of bioavailability of ISDN, 2-ISMN, and 5-ISMN from the three formulations as estimated from the areas under the plasma drug concentration - time curves were not statistically significantly different (p greater than 0.05). The ratios for relative drug bioavailability from the respective formulations were similar whether ISDN, 2-ISMN, or 5-ISMN data were used for calculation. Reasons are discussed for the biphasic decline of plasma ISDN concentrations (half-lives 26 min and 5.1 h) obtained after administration of the standard-release formulation.

Adolescent↗
PubMed1983

Who is the patient? A family case study of a recurrent dilemma in family practice.

This article presents a family case study of a recurrent dilemma in family medicine. The ethical dilemma involves what role the physician should play in mediating a conflict in a family when the health needs and wishes of the individual patient do not parallel those of the other family members. Who is the patient, the individual or the family? It is the authors' conviction that in meeting the needs of the presenting patient, the family context is of great importance. To this end, the authors delineate a framework for analyzing ethical conflicts of this nature, utilizing key ethical principles in combination with a systems perspective to aid in the clarification of such choices. The principles examined include autonomy, nonmaleficence, and justice. Also taken into account are the relevant facts, values, and the biases of the physician. Exploration of these factors allows the physician a comprehensive and logical approach for resolving such conflicts. Such a framework, however, can only provide guidance; it does not guarantee easy or uniformly acceptable alternatives to difficult issues.

Aged↗
PubMed1983

[Pharmacokinetics of 14C-isosorbide dinitrate after administration in various sustained-release formulations].

To study the influence of various in vitro release rates and of coadministration with food on bioavailability of isosorbide dinitrate (ISDN; isoket retard 40) and its mononitrate metabolites from sustained-release formulations the pharmacokinetics of two experimental batches of tablets with different release rates containing 40 mg 14C-ISDN each were studied in six human volunteers. One of the formulations was not only administered after fasting but aslo with a standard meal. In all cases approx. 80% of the administered radioactivity were recovered in the urine and 5% in the faeces during 3 days demonstrating extensive absorption. Any influence of release rates or food on absorption rates could not be detected. When administered after fasting either formulation was bioequivalent. Coadministration of a meal enhanced ISDN plasma levels in some subjects although no statistically significant difference in extent of bioavailability was observed. Availability of the mononitrates was unaffected by food.

Adult↗
PubMed1982

Sulfhydryl groups of native myosin and of the myosin heavy chains from Physarum polycephalum compared to vertebrate skeletal, smooth, and non-muscle myosins.

Although a previously reported analysis of Physarum myosin detected no cysteine residues in the molecule, the myosin ATPase activity was inhibited by p-chloromercuribenzoate. We have re-examined this apparently contradictory finding. We found highly purified plasmodial myosin to be very sensitive to N-ethylmaleimide inhibition of the K+, Ca2+ -activated ATPase. An estimate of the number of reactive sulfhydryls of the native myosin using Ellman's reagent showed only 1.5 mol 11 min-reactive sulfhydryl/mol as compared to 4.5 for chicken breast myosin in 5 min. 3H- and 14C-labelled N-ethylmaleimide was used to estimate the total sulfhydryls of the SDS-denatured heavy chains. Plasmodial myosin heavy chains bound 10-13% of the N-ethylmaleimide bound by chicken breast myosin heavy chains. Smooth muscle myosin heavy chains as well as heavy chains of embryonic chicken presumptive myoblasts had 65-70% of the reactive groups of chicken myotube myosin heavy chains. Amino acid analyses of purified Physarum myosin showed that some preparations contained cysteic acid residues even before performic oxidation. After the performic oxidation a mean value of 3 mol cysteic acid per 10(5) g Physarum myosin was found, or less than half that reported for striated muscle myosin. Our results show that in the sulfhydryl-poor plasmodial myosin each heavy chain contains at least two sulfhydryls, and probably more, but that there is variable oxidation of the total sulfhydryls. It has been reported that plasmodial myosin lacks rapidly reacting sulfhydryls groups when tested with an ATP analogue which reacts with light chains of vertebrate muscle myosins. Therefore, the 1-2 sulfhydryls of plasmodial myosin which react rapidly with Ellman's reagent appear to be on the heavy chain. Our results also suggest that during development of myotubes changes occur in the myosin heavy chains.

Amino Acids↗
PubMed1982

Bioavailability of indomethacin from two multiple-units controlled-release formulations.

Two multiple-units controlled-release indomethacin capsule formulations containing enteric-coated pellets were bioequivalent to a standard capsule formulation (taken as the reference) in respect of extent of bioavailability in a crossover study with normal human subjects. However, drug absorption from the enteric-coated pellet formulations was slower, when compared to that from the standard reference capsule. The standard reference capsule released 85% of its drug content in vitro during 10 min at pH 6.5 and 98% during 1 h at pH 7.5. On enteric-coated pellet capsule formulation (I) released 77% during 1 h at pH 6.5 and the other (II) released 10% during 1 h at pH 6.5. Release of drug from each capsule of enteric-coated pellets was complete during 1 h at pH 7.5. Although differences in areas under the plasma indomethacin concentration-time curves were not significantly different, the peak plasma levels and the times of their occurrence indicated that the absorption rates of indomethacin decreased in the order, reference formulation greater than pellet formulation I greater than pellet formulation II, which was the same rank order as that of their dissolution rates in vitro. The data indicated that multiple units controlled-release formulations represent a reliable and reproducible source of indomethacin, which by avoiding extremes of local or systemic drug concentrations also should be better tolerated by individuals susceptible to unwanted gastrointestinal and centrally-mediate side-effects.

Adult↗
PubMed1981

Clinical and secretory differences in pancreatic cancer and chronic pancreatitis.

The differential diagnosis between chronic pancreatitis and pancreatic cancer can be very difficult. In 60 patients with either of these conditions, who had satisfactory ERCP study, clinical features were correctly matched with the final diagnosis by discriminant analysis in 44 (73%). The sensitivity of ERCP radiographic findings in pancreatic cancer was 80% and sensitivity of cytology was 54%. To see if exocrine function was specific for cancer, fresh pancreatic secretions were aspirated in 27 patients at the time of ERCP. By isoelectric focusing, a pattern of extreme zymogen depletion was observed in chronic alcoholic pancreatitis (Group 1), pancreatic cancer (Group 2), and chronic nonalcoholic pancreatitis (Group 3). The three groups were not distinguishable. By contrast, significant changes in albumin, IgG and IgA concentrations were seen in Group 2. The albumin level was over ten-fold greater than in Groups 1 and 3 (p less than 0.02 and less than 0.05). The IgG was seven-fold and two-fold greater (p less than 0.01 and greater than 0.2) and the IgA was 15-fold and six-fold greater (p less than 0.002 and less than 0.05) than in Groups 1 and 3, respectively. The two groups of pancreatitis had similar concentrations of albumin and IgA. The ratio of albumin to IgG was also different in Group 2 from the other groups, suggesting different mechanisms for the appearance of proteins in pancreatic secretions. Nonzymogen protein levels can distinguish chronic pancreatitis from pancreatic cancer, and further study of them may identify useful tumor-specific markers.

Albumins↗
PubMed1981

Leukemic optic nerve infiltration 17 months after cessation of therapy.

A patient with leukemic optic nerve infiltration is presented. It occurred as an isolated manifestation of leukemia 17 months after therapy for acute lymphocytic leukemia was discontinued. Therapy with prednisone and vincristine was effective in reducing optic nerve infiltration in a short period of time. This observation leads to the conclusion that the optic nerve does not belong to the pharmacological sanctuary.

Antineoplastic Agents↗
PubMed1980

Plasma concentration and disposition of buprenorphine after intravenous and intramuscular doses to baboons.

Buprenorphine is a newly-developed strong analgesic. A selected ion monitoring method has been developed to measure its plasma levels over the concentration range 20-3000ng ml-1. Six baboons each received intravenous and intramuscular doses of buprenorphine hydrochloride at a level of 5mg/kg in a cross-over study. The mean peak plasma concentrations (+/-standard deviation) were 2290 +/- 357ng ml-1 and 805 +/- 416ng ml-1 respectively and the corresponding times to the peak levels were 4.0 +/- 1.5 minutes and 30.3 +/- 24.6 minutes suggesting the rapid release of the drug from intramuscular sites. Comparison of areas under the plasma concentration versus time curves to 24 hours after dosing showed the mean bioavailability of buprenorphine from the intramuscular doses was 70% of that from the reference intravenous doses.

Animals↗