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Biomedical subjects

T W Wilson

Publications and source records attributed to T W Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1976

The necessity of drug level monitoring in anticonvulsant drug therapy.

A survey of 'steady-state' serum levels of anticonvulsant drugs from 221 epileptic patients at a university hospital was conducted. Serum concentrations of phenobarbital, primidone, and diphenylhydantoin were determined by a gas chromatographic method. Sixty-five percent (130) of the patients receiving diphenylhydantoin had levels below the therapeutic range of 10-20mug/ml. Subtherapeutic levels appear to be due to inadequate dosage adjustment. Only 25% (33) of the patients receiving phenobarbital had levels below the therapeutic range. Serum levels of diphenylhydantoin or phenobarbital could not be predicted from dosage. Most patients received two or more drugs. Over 10% of the patients had potentially toxic levels of anticonvulsant drugs. High levels of diphenylhydantoin were easily recognized clinically but high levels of phenobarbital were not.

Body Weight↗
PubMed1976

Oral ingestion of narcotic analgesics by rats.

Rats drank solutions of narcotic analgesics as the only drinking fluid available in their cages. Relative to their daily water intake before the drug solutions were introduced, the rats drank more etonitazene solution, less methadone solution, and about the same volume of morphine, meperidine and levorphanol solution as water, although some rats would not drink the higher concentrations of morphine (1.0 mg/ml), levorphanol (1.0 mg/ml) and methadone (1.0 mg/ml). When naloxone (1.0 mg/kg) was administered after 12 days of drinking the drug solutions, the severity of the abstinence syndromes based on scoring of symptoms and on weight loss was morphine greater than or equal to etonitazine greater than levorphanol greater than meperidine greater than methadone. The animals showing the most severe syndrome after naloxone usually consumed more drug solution than usual during the next 24 hours, so that body weights were normal at the end of the 24-hour period. Nonprecipitated abstinence was also studied in these rats by replacing the drug solutions with water 3 to 5 days after the naloxone injection. Rats that had been drinking morphine, etonitazene and levorphanol lost weight for 2 or 3 days and then began to regain their lost weight. In contrast, rats which had been switched from methadone and meperidine solutions to water gained weight rapidly. Morphine and etonitazene drinkers which had been switched to water drank a lesser volume of water than they had been drinking of drug solution whereas some ex-methadone drinkers drank more water.

Administration, Oral↗
PubMed1975

A gas chromatographic method for measuring 6-mercaptopurine in serum.

A method is presented for the measurement of 6-mercaptopurine (6-MP) in serum. Serum samples containing the drug were treated with dithioerythritol and saturated with ammonium carbonate. 6-MP was then extracted from the serum with a mixture of isopropanol-ethyl acetate (1:1, v/v) containing 0.01% ethanethiol. The solvent was evaporated, the residue dissolved in dilute hydrocholoric acid, washed with chloroform, and extracted with ethyl acetate. 6-MP was derivatized with trimethylanilinium hydroxide and measured gas chromatographically. The sulfhydryl-protecting reagents, dithioerythritol and ethanethiol, were added to prevent the decomposition of 6-MP. The extraction and clean-up method recovered 78 +/- 2% (S.E.) of the 6-MP present. Tracer amounts of [8-14C]6-MP served as the internal standard during the extraction part of the method. Theophyline was used as the internal standard during the gas chromatographic analysis. The standard curve obtained from the gas chromatograph was linear between 0.5 and 20 mug/ml of 6-MP. Serum samples were stored in the freezer for two weeks without significant loss of drug. No interference was encountered from normal serum constituents or xanthines, such as caffeine or theophylline added to serum.

Chromatography, Gas↗
PubMed1975

Effect of dosage regimen on natriuretic response to furosemide.

We have examined the differences in urinary excretion of water, sodium, potassium, chloride, urea, and creatinine produced by different dosage regimens offurosemide in normal volunteers. Three oral dosage regimens were compared: 20 mg daily, 20 mg twice daily, and 40 mg daily. Furosemide, 20 mg, did not produce a significant weight loss, diuresis, or natriuresis in 12 normal subjects. With 40 there was a significant weight loss, diuresis, natriuresis, and chloruresis over 24 hr. Comparison of the divided regimen with 40 mg daily revealed significantly greater sodium excretion, and chloride excretion with 20 mg twice daily. The divided dosage regimen produced a different pattern of diuresis with most of the sodium and water excretion occurring after the second dose. These differences in response to different regimens are predictable from pharmacokinetic considerations and may have clinical significance.

Administration, Oral↗
PubMed1975

Some pharmacological properties of althesin (CT1341) in man.

Althesin in dose ranges of 40, 60 and 80 mul/Kg was administered to six healthy unpremedicated volunteers according to a balanced incomplete block design. Both subjective and objective changes resulting from the administration of the agent were studied and analyzed. In the dose ranges used, Althesin was found to have no deleterious effects on heart rate, respiratory rate or blood pressure and apnoea only occurred in one patient who had an end-expiratory CO2 level lower than normal, due to preanaesthetic hyperventilation. The onset of sleep is prolonged with Althesin at the injection rate of 1 ml/10 secs. The onset of anaesthesia is not influenced by the total dose, but the sleep time is directly proportional to the dose injected. Auditory evoked responses tended to lie on a curve which might indicate that with increasing dose the time to reappearance of these responses is not correspondingly prolonged. However, this last observation must be confirmed by studies on a larger scale.

Adult↗
PubMed1975

Urinary prostaglandins. Identification and origin.

Human urine was analyzed by mass spectrometry for the presence of prostaglandins. Prostaglandin E2 and F2alpha were detected in urine from females by selected ion monitoring of the prostaglandin E2-methylester-methoxime bis-acetate and the prostaglandin F2alpha-methyl ester-Tris-trimethylsilylether derivative. Additional evidence for the presence of prostaglandin F2alpha was obtained by isolating from female urine an amount of this prostaglandin sufficient to yield a complete mass spectrum. The methods utilized permitted quantitative analysis. The origin of urinary prostaglandin was determined by stimulating renal prostaglandin synthesis by arachidonic acid or angiotensin infusion. Arachidonic acid, the precursor of prostaglandin E2, when infused into one renal artery of a dog led to a significant increase in the excretion rate of this prostaglandin. Similarly, infusion of angiotensin II amide led to a significantly increased ipsilateral excretion rate of prostaglandin E2 and F2a in spite of a simultaneous decrease in the creatinine clearance. In man, i.v. infusion of angiotensin also led to an increased urinary eliminiation of prostaglandin E. These results show that urinary prostaglandins may originate from the kidney, indicating that renally synthesized prostaglandins diffuse or are excreted into the tubule. Thus, urinary prostaglandins are a reflection of renal prostaglandin synthesis and have potential as a tool to delineate renal prostaglandin physiology and pathology.

Angiotensin II↗
PubMed1973

Radioimmunoassay for measurement of gentamicin in blood.

Gentamicin toxicity has been shown to be related to high concentrations in serum. Because there is a narrow range between its therapeutic and toxic levels, serial monitoring of gentamicin is the most reliable method of guiding therapy. Microbiological assays commonly in use do not afford the desired speed and accuracy, and results may be difficult to interpret in the presence of other antimicrobials. Hence, a rapid, sensitive, and highly specific radioimmunoassay for measurement of gentamicin in serum has been developed. Antibody to gentamicin was raised in rabbits by using a gentamicin-albumin conjugate. Tritiated gentamicin (specific activity 1.0 Ci/mM) competes with unlabeled gentamicin for binding sites on the antibody. Dextran-coated charcoal separates the unbound from antibody-bound gentamicin. Serum levels of gentamicin are determined by comparison with a standard curve. This method can detect concentrations as low as 0.01 mug/ml. Results of a 24-tube run can be obtained in 1 h, thus allowing modification of gentamicin dosage to advantage.

Aged↗
PubMedDate not supplied

The relative bioavailability of a commercial propranolol hydrochloride tablet in man.

A relative bioavailability study of conventional tablet of propranolol hydrochloride was conducted in a group of 18 healthy volunteers employing the innovator's product as the reference tablet formation. Based on plasma levels of propranolol for the 24 h following administration of 2 x 40 mg oral propranolol hydrochloride tablets, the relative extent of availability was shown to be 100.8 per cent for the test tablet formulation; no significant differences were detected between formulations with respect to any of the pharmacokinetic parameters examined. Large intersubject variations in plasma propranolol concentrations and the subsequently calculated areas under the plasma concentration/time curves were attributed to substantial presystemic biotransformation differences.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics of glucuronidation of propranolol following oral administration in humans.

Pharmacokinetic and bioavailability parameters of propranolol were estimated in 10 healthy adult subjects after single oral doses of two commercial tablet formulations of propranolol hydrochloride (2 X 40 mg). Plasma concentrations of propranolol were determined by a high-performance liquid-chromatographic (HPLC) assay. Peak plasma concentrations of propranolol glucuronide were 6-8 times those of the corresponding peak propranolol plasma concentrations. The mean resident time (MRT) of propranolol and of propranolol glucuronide was determined for each subject for both formulations. The MRT of the parent drug was found to be longer than the MRT of the glucuronide metabolite for each of the subjects examined. Statistical moment analysis indicated that this phenomenon is attributable to extensive presystemic glucuronidation of the parent drug.

Administration, Oral↗
PubMedDate not supplied

Social factors in alexithymia.

Social characteristics of alexithymic individuals were examined in a population-based study of 2,682 middle-aged men from Eastern Finland. Alexithymia, referring to difficulties in identifying and verbally describing inner feelings, was assessed using the Toronto Alexithymia Scale (TAS). Men whose high TAS score suggested reduced ability in verbal emotional expression were more often unmarried and had low levels of social contacts and acquaintances. Education, income, and occupational status were inversely related to the TAS score. These associations remained statistically significant after adjustment for confounding factors. The results suggest that alexithymia could be viewed not only as a psychological phenomenon, but also partly as a socially determined one.

Adult↗
PubMedDate not supplied

A biomechanical analysis of matched bone-patellar tendon-bone and double-looped semitendinosus and gracilis tendon grafts.

Biomechanical testing was done on 15 matched pairs of central-third bone-patellar tendon-bone and double-looped semitendinosus-gracilis grafts harvested from 15 cadaveric knees. Load to failure, composite graft stiffness, and the modulus of elasticity were calculated for each graft. Specimens were from 2 female and 13 male donors (average age, 40 years; range, 17 to 53). Average load to failure for the patellar tendon grafts was 1784 N (+/- 580), compared with 2422 N (+/- 538) for the hamstring tendon grafts (significantly different). There was no statistically significant difference in stiffness between grafts (patellar tendon, 210 N/mm; hamstring tendon, 238 N/mm). The elastic modulus was 225 MPa (+/- 129) for the patellar tendon grafts and 145 MPa (+/- 58) for the hamstring tendon grafts (significantly different). The average cross-sectional area for the hamstring tendon grafts was 57 mm2, compared with the 45 mm2 for the patellar tendon grafts. The hamstring tendon grafts were significantly stronger than the matched central-third patellar tendon grafts, but the two grafts were similar in stiffness. The patellar tendon grafts had a higher modulus than the hamstring tendon grafts.

Adult↗
PubMedDate not supplied

Pheochromocytoma: an unusual presentation and sequela.

A 40-year-old male presenting with exercise-induced headaches was found to have a pheochromocytoma which was subsequently removed. His blood pressure was never recorded as elevated. He went on to develop recurrence of asthma, which had been absent for at least 20 years, 48 h postoperatively. This is the first case of pheochromocytoma manifesting as exercise-induced headache in the absence of detectable hypertension.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Predicting success in antihypertensive drug therapy: the importance of nondrug variables.

The hypothesis of this study was that specific lifestyle patterns would be predictive of, or increase the risk for, uncontrolled hypertension in drug-treated hypertensive subjects. By means of a previously validated questionnaire, alcohol consumption, smoking, exercise, calcium intake, sodium intake, caffeine intake, body weight pattern and perceived stress level were evaluated in 364 subjects who attended a hypertension clinic in a large urban teaching hospital. The subjects were divided into controlled and uncontrolled categories on the basis of a clinic blood pressure reading. The number of prescribed drugs was not different between the two groups. Stratified analysis identified a high perceived stress level, a high calcium intake, and a lower body mass index as predictive of uncontrolled hypertension. Other variables showed no significant correlation. The conclusion of the study is that traditional risk factors for hypertension may assume less importance in drug-treated hypertensive patients than in untreated hypertensive patients.

Adolescent↗