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Biomedical subjects

K Wilson

Publications and source records attributed to K Wilson.

At least 325 records · Page 18Linked to original sources
PubMed1981

The kinetics of the urinary excretion of the N-oxide and glucuronides of methaqualone in man.

The urinary excretion of the N-oxide and the glucuronides of five C-monohydroxy metabolites of methaqualone has been studied following the oral administration of a single dose of the drug. The apparent first order rate constants for the excretion of each metabolite (kme) were shown to be numerically smaller than the overall elimination rate constant for methaqualone (k10). The Kme values tended to be greater than or equal to the corresponding apparent first order rate constants for the formation of the metabolite (km) but corresponding kme and km values were always of the same order magnitude. The kme values for the glucuronides were much smaller than the literature kme value for paracetemol glucuronide. The rate of renal elimination of the metabolites was variably sensitive to urine flow but over a period of time of 8 hours or greater the total amount of metabolite recovered in the urine was was independent of the total urine volume.

Adult↗
PubMed1981

A single-blind crossover trial of the anti-inflammatory drug sodium meclofenamate and placebo, including an evaluation of hand grip and of lymphocyte responsiveness.

A single-blind crossover trial was carried out in 21 patients with active rheumatoid arthritis to assess the effectiveness and tolerance of sodium meclofenamate (300 mg per day) compared with placebo. After a 1-week washout period patients had two periods of active medication, each of 2 weeks, separated by 1 week on placebo. Morning stiffness, walking speed, pain score, patient impression of response, joint tenderness and power, work and maximum grip strength achieved by hand grip were all improved by sodium meclofenamate and an anti-inflammatory effect of the drug was demonstrated, with some reduction in the swelling of PIP joints. There was no advantage in assessing pain on full movement of the small joints of the hands in addition to direct tenderness. Power, work and rate of grip release achieved during hand grip provided more information about hand function than maximum grip strength alone. Lymphocyte transformation to non-specific mitogens was enhanced by the drug. Twelve patients had some form of gastro intestinal complaint during the study and it is suggested that diarrhoea is likely to prove to be the major limiting factor of acceptance by some patients.

Adult↗
PubMed1980

Peptides isolated from human liver with specific inhibitory effects on reassociation/reactivation of in vitro dissociated lactic dehydrogenase (LDH-M4 and -H4) isozymes.

Two different peptides have been purified from human liver, similar to those previously reported (Schoenenberger, G.A., and Wacker, W.E.C. (1966) Biochemistry 5, 1375--1379) to be present in human urine, which may serve as metabolic regulators of lactate dehydrogenase (EC 1.1.1.27) isoenzymes (LDH-M4 = muscle type; LDH-H4 = heart type). By trichloroacetic acid precipitation, ultrafiltration, Sephadex G-25 and Bio-Gel P-2 columns, affinity chromatography on immobilized LDH-isozymes and HPLC two peptides which differed with respect to molecular weight, retention on the affinity columns and amino acid composition were isolated. No effect was observed when native, tetrameric lactate dehydrogenase was incubated with these peptides. However, when lactate dehydrogenase was dissociated to monomers at low pH and allowed to reassociate by adjusting the pH to 7.5 complete inhibition of the reactivation occurred when the inhibitors were incubated together with respective reassociating monomeric isozymes. The two peptides showed no cross-specificity, i.e. each peptide exhibited inhibitory activity only on one of the two isozymes LDH-M4 or LDH-H4. From the amino acid analyses, gel filtrations and PAGE + SDS, molecular weights of 1800 for the M4 and approximately 2700 for the H4 inhibitor were calculated. An apparent Ki of approximately 3 X 10(-5) mM for the H4 and approximately 7 X 10(-5) mM for the H4 inhibitor was estimated. The interaction of the inhibitors with the enzyme system showed strong cooperativity with Hill coefficients of 2.9 (LDH-M4-specific) and 2.4 (LDH-H4-specific). Mathematical modelling of the reassociation and reactivation of lactate dehydrogenase and its specific inhibition by the peptides led to the conclusion that the peptides react with monomers, dimers or a transition state during the tetramerisation process. kappa 1 for the dimerisation step of M4 = 2.0 X 10(5) M-1 . S-1 and of H4 = 8.2 X 10(4) M-1 . S-1; kappa 2 for the tetramerisation step of M4 = 2.8 X 10(5) M-1 . S-1 and of H4 = 1.2 X 10(5) . M-1 S-1, were calculated, the second step still being the faster one (Rudolf, R. and Jaenicke, R. (1976) Eur. J Biochem. 63, 409--417).

Amino Acids↗
PubMed1980

The effects of extremes of age on drug action.

Many examples of age-related differences in the response of individuals to a particular drug have been documented. In many cases these differences can be related to modified distribution, metabolism or excretion of the drug. There is evidence that in neonates and the elderly, the extent and rate of these processes are less than those in older children and young adults. However, in a given age group there is no consistent trend for all drugs. In some cases the increased plasma concentration of the drug would be regarded as an advantage as it prolongs the response, but it is certainly not true for drugs such as streptomycin, warfarin and the hypoglycemic agents. Two points which emerge from the results of many studies with neonates and the elderly are that interindividual variations in plasma half-lives, metabolite and drug excretion and protein binding are significantly larger than those in young adults and that in the case of the elderly, chronological age does not necessarily reflect biological age. In combination these factors emphasise the importance of individual drug monitoring of plasma levels and hence of knowing the pharmacokinetic constants of the drug in the individual patient. In clinical practice, the dose of a drug is most commonly calculated on the basis of body weight or surface area. This is generally perfectly acceptable for older children and adults, but is not always a reliable formula for neonates and the very old. Simple changes in such parameters as urine pH can override calculations based upon body size.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1979

The metabolism of methaqualone in patients with biliary cirrhosis or secondary carcinoma of the liver.

The metabolism of methaqualone has been studied in three patients with secondary carcinoma of the liver and two with biliary cirrhosis. The urinary excretion of five C-monohydroxy metabolites and the N-oxide was studies in the 24 h period immediately after oral dosing with 250 mg methaqualone (Melsed). In both patients with biliary cirrhosis and one with primary carcinoma of the bile duct or pancreas with secondaries in the liver the pattern of metabolites was normal. In a patient with oat cell carcinoma with secondaries in the liver some metabolite patterns were disturbed and increased metabolite excretion occurred. A patient with primary carcinoma of the breast with secondaries in the liver gave a completely abnormal metabolite pattern.

Adult↗
PubMed1979

Factors determining peripheral vein tolerance to amino acid infusions.

The tolerance of peripheral veins to intravenous infusions was evaluated. Of 83 infusions studied, 67 contained amino acids. Phlebitis occurred more commonly with the use of solutions that contained the amino acids. The important factors in the production of phlebitis by amino acid solutions were osmolarity, and the amount of potassium infused per day. Phlebitis was universal when osmolarity exceeded 600 mOsm. Other factors that promoted phlebitis were the presence of antibiotics and the size of the vein.

Amino Acids↗
PubMed1979

Diet-related toxemia in pregnancy. I. Fat, fatty acids, and cholesterol.

Toxemia in pregnancy (preeclampsia)is characteristerized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In three successive trials over three consecutive years, the dietary intake of a selected number of young pregnant women attending a Maternal and Infant Care Program at Tuskegee Institute were evaluated for total lipids, individual fatty acids, and cholesterol. Women with toxemia or with any of the individual symptoms were identified and women without toxemia or these symptoms served as controls. Results were variable from repetition to repetition in all but the toxemia group and the edema group. The consumption of total lipids and cholesterol was significantly greater in all three trials by both the toxemia and edema groups. Also, total saturated, monounsaturated, and polyunsaturated fatty acids were eaten in greater amounts. The greatest differences were in palmitic acid, stearic acid, oleic acid, and linoleic acid. The proportion of unsaturated fatty acids consumed in all groups was very low. All differences could be attributed primarily to breakfast and dinner meals and were found in the milk, meat, and egg food groups. Although satistical correlations were found between lipid intake and toxemia of pregnancy any specific relationship between the two is still unclear.

Adolescent↗
PubMed1979

Disseminated gonococcal infections (DGI).

Neisseria gonorrhoeae infects superficial membranes of the eyes, oropharynx, genital tract, and rectum prior to dissemination. Gonococcal isolates cultured from patients with disseminated gonococcal infections (DGI) show resistance to serum bacteriolysis, are very sensitive to penicillin, and have characteristic growth requirements for certain amino acids. DGI is characterized by recurrent chills and fever, polyarthralgias and/or polyarthritis (with effusions), and skin lesions. The skin manifestations of DGI include vesicopustules, hemorrhagic bullae, and petechiae. These lesions are found over the juxta-articular areas of the hands (extensor surfaces) or the feet (dorsal aspects). Focal and disseminated gonococcal infections are now treated with several types of penicillin regimens, tetracycline, or spectinomycin.

Anti-Bacterial Agents↗
PubMed1978

The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide.

A peptide which induces slow-wave EEG (sleep) after intraventricular infusion into the brain has been isolated from the extracorporeal dialysate of cerebral venous blood in rabbits submitted to hypnogenic electrical stimulation of the intralaminar thalamic area. It was shown by amino-acid analysis and sequence determination to be Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu and named "Delta Sleep-Inducing Peptide" (DSIP). This compound was synthesized as well as 5 possible metabolic products (1--8, 2--9, 2--8, 1--4 and 5--9), 2 nonapeptide analogues (with one and two amino-acids exchanged) and a related tripeptide (Trp-Ser-Glu). All 9 synthetic peptides were infused intraventricularly in rabbits (6 nmol/kg in 0.05 ml of CSF-like solution over 3.5 min) and tested under double-blind conditions. A total of 61 rabbits including controls were used. The EEG from the frontal neocortex and the limbic archicortex were subjected to direct fast-Fourier transformation and analyzed by an 1108 computer system. A highly specific delta and spindle EEG-enhancing effect of the synthetic DSIP could be demonstrated. The mean increase of EEG delta activity reached 35% in the neocortex and limbic cortex as compared to control animals receiving CSF-like solution or any of the other 8 peptides. The final chemical characterization of the synthetic DSIP revealed that only the pure alpha-aspartyl peptide is highly active in contrast to its beta-Asp isomer. A neurohumoral modulating and programming activity was suggested.

Amino Acid Sequence↗
PubMed1978

Metabolism of methaqualone in geriatric patients.

The urinary excretion of five C-monohydroxy metabolites and the N-oxide of methaqualone has been measured in a group of eleven geriatric patients aged 71--90 years. The total excretion of the six metabolites in 24 h after the oral administration of a single dose was approximately one-half of that in a group of young healthy adults. The relative importance of the six metabolites was 4'-hydroxy greater than N-oxide greater than 2'-hydroxymethyl = 3'-hydroxy greater than 6-hydroxy = 2-hydroxymethyl which was the same order as that in young adults. The ratio of C-to N-oxidation was also the same in the two groups. There was no impairment of conjugation of the C-hydroxy metabolites with glucuronic acid in the geriatric group but there was greater interindividual variation in metabolite excretion. There was also evidence for delayed metabolism in the geriatric patients.

Aged↗
PubMed1978

Inter- and intra-individual variation in the metabolism of methaqualone in man after a single oral dose.

The urinary excretion of five C-monohydroxy metabolites and the N-oxide metabolite of methaqualone in the 24 h period immediately after oral dosing with 250 mg methaqualone (Melsed) has been measured in ninteen healthy adults (13 male, 6 female) to assess interindividual variations and in five adults (3 male, 2 female) on five separate occasions to assess intraindividual variation. The overall importance of the six metabolites was 4'-hydroxy greater than N-oxide greater than 2'-hydroxymethyl greater than 3'-hydroxy greater than 6-hydroxy = 2-hydroxymethyl. Variations in this order both within the 24 h period and within each of the three eight-hour periods constituting the 24 hours were minor and variations in the absolute amount of each metabolie excreted ranged from two to three-fold. Intraindividual variations were generally smaller than interindividual variations and for each individual the pattern of metabolism was similar on the five occasions. There is evidence that the C-oxidation of methaqualone may be more sensitive to cyclical variations in hormone levels than is N-oxidation.

Adult↗
PubMed1978

Congenital X-linked adrenal hypoplasia.

Fetal adrenal hypoplasia should be considered in pregnant patients with family histories of the condition and/or following observation of drastically reduced maternal estriol excretion. Antepartum diagnosis is important in the clinical management of these infants since deteriorating adrenal function frequently follows an asymptomatic period during the early neonatal life. Antepartum and neonatal diagnostic studies can identify fetal adrenal hypoplasia.

Adrenal Insufficiency↗