Search PubMed⌕ Search

Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 829 records · Page 46Linked to original sources

Clinical pharmacology of GP53,633--a new non-steroidal anti-inflammatory drug--in patients with rheumatoid arthritis.

GP53,633 is a new basic non-steroidal anti-inflammatory drug showing analgesic and anti-inflammatory activity in animal models. Pharmacokinetic studies in 6 patients with rheumatoid arthritis show it to be rapidly absorbed with a short half life (approximately 2 hours). No change in pharmacokinetics is seen over a two week treatment period. Clinical parameters of inflammation were reduced and no adverse reactions were seen.

Adult↗

Selection and microencapsulation of an "NADH-oxidizing" bacterium and its use for NAD regeneration.

An alternative approach to the regeneration of coenzymes is described here using immobilized microorganisms possessing "NADH-oxidase" function. Bacteria containing NADH-oxidase activity are immobilized by microencapsulation within artificial cells. In this form, the microencapsulated bacteria can recycle NADH back to NAD in the presence of molecular oxygen as an electron acceptor. The only byproduct of the recycling reaction is water. In order to perform the biological regeneration of NAD, the activity of NADH-oxidase was investigated in 13 strains of aerobic bacteria and yeast. The NADH-oxidizing bacteria Leuconostoc mesenteroides exhibited the highest activity among the microorganisms tested. The permeabilized bacteria showed 10% of their initial activity after microencapsulation. Light and electron microscopy studies of bacteria loaded microcapsules have been done. Enzymatic properties of microcapsule-immobilized bacteria were investigated in comparison with those of the free enzyme complex. Leuconostoc mesenteroides, containing NADH-oxidase, has been microencapsulated together with 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH) for stereospecific steroid oxidation. In a batch reactor, 2 mg of NAD, with recycling, allowed the same substrate consumption as 4.4 mg of NAD without recycling. The microencapsulated system can be used repeatedly. The system is functional for 10 h, during which time each molecule of NAD has been used 7.6 times.

3-Hydroxysteroid Dehydrogenases↗

Radiochemical synthesis of DL-canaline and the colorimetric assay of canaline.

A procedure is available for the production of DL-[carboxy-14C]canaline from [14C]cyanide by reaction of ethyl N-hydroxyacetimidate and acrolein to form ethyl N-[3-oxopropoxy]acetimidate. The reaction product is converted to the nitrile and then to the hydantoin derivative of DL-canaline; alkaline hydrolysis produces the free amino acid (2-amino-4-aminooxypropionic acid). This procedure can be extended to the production of DL-[carboxy-14C]canavanine by guanidination of C-1-labeled DL-canaline with O-methylisourea. A markedly improved colorimetric assay for canaline has been achieved by a procedure involving carbamylation of canaline with cyanate to form O-ureidohomoserine (2-amino-4-ureidooxybutyric acid). Colorimetric analysis of the latter amino acid markedly enhances the sensitivity, reproducibility, and accuracy of the analysis of L-canaline from biological materials.

Aminobutyrates↗

Prosthetic valve endocarditis caused by Trichosporon cutaneum.

We report, to our knowledge, the first case of Trichosporon cutaneum endocarditis which developed in a 58-year-old woman 14 months after mitral valve replacement. The patient had not had antibiotic therapy. She was treated with an oral antifungal agent, ketoconazol, and prosthetic valve replacement. The initial outcome was favorable, but she died 5 months later of aortic valve endocarditis. Fungal infection was documented by isolation of the fungus from blood cultures, by anatomical and pathological examination and by the changes in serology.

Aortic Valve↗

Electrophysiological and ultrasonic correlates of reproductive behavior in the male rat.

The purpose of the present study was to examine the electrophysiological correlates of copulatory behavior in the rat and correlate brain electroencephalographic (EEG) activity with the ultrasonic vocalizations that have been shown to play a major role in the integration of mating behavior. Ultrasonic vocalizations of male rats with chronically implanted hippocampal and cortical electrodes were monitored during mating with a female rat. Hippocampal theta rhythms were significantly correlated with high activity, mounting, intromissions, and preejaculatory excitatory behavior and were also significantly associated with 50-kHz short ultrasonic vocalizations. Postmount or postintromission behaviors (grooming, exploration) were closely correlated with an absence of ultrasonic vocalizations and the onset of irregular low-amplitude hippocampal EEG recordings. Long 22-kHz vocalizations occurred in all tests during the postejaculatory refractory period. Shorter 22-kHz vocalizations occurred during mating and were associated with unsuccessful intromissions or mounting attempts. Postejaculatory long 22-kHz vocalizations were significantly associated with irregular high-amplitude hippocampal EEG tracings, and preejaculatory short 22-kHz vocalizations were also accompanied by sleep-like irregular high-amplitude hippocampal EEG tracings with cortical spindling. The correlation of ultrasonic vocalizations with electroencephalographic and behavioral manifestations of central arousal and inhibitory processes suggests that these vocalizations are indicators of the sexual arousal of the mating pair.

Animals↗

Pharmacokinetics of cefotaxime in neonates.

The effects of gestational age on the pharmacokinetics of cefotaxime and its desacetyl metabolite during the first days of life was investigated in a group of four full-term infants and 12 preterm infants of less than 35 weeks gestation. Half of the preterm infants had received betamethasone, a drug known to facilitate hepatic microsomal drug metabolism, whilst the others had not. No significant differences in the pharmacokinetics of cefotaxime were observed between the various groups, with elimination half-life (T 1/2 beta) of cefotaxime ranging from 4.04 +/- 1.52 to 4.56 +/- 1.31 h. The desacetyl metabolite of cefotaxime was present in all post-dose serum samples, irrespective of the gestational age of the baby. Its formation was apparently unaffected by prior exposure to betamethasone. The elimination half-life of cefotaxime is significantly longer in newborn infants than in older children or adults, this increase probably results from decreased renal excretion of the drug, rather than from immaturity in its metabolism. A dose of 50 mg/kg of cefotaxime given every 12 h is appropriate for infants of less than seven days old.

Aging↗

Thrombokinetics in patients with rheumatoid arthritis treated with D-penicillamine.

The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression.

Adult↗

Theophylline metabolism in preterm neonates during the first weeks of life.

The effects of prenatal steroids on theophylline metabolism in infants of 27-32 weeks gestation was studied. Although in utero exposure to betamethasone was associated with a more mature theophylline metabolite pattern in the first days of life, initial elimination half-life (t1/2 beta) did not differ significantly between groups. By the second or third week of life the metabolite pattern was similar in all infants. The decline in t1/2 beta seen during theophylline treatment was not directly related to increased metabolite formation. These data suggest that other factors, such as renal clearance, are more important in determining the pharmacokinetics of theophylline in neonates than is hepatic metabolism.

Betamethasone↗

A post-anaesthetic scoring system.

A post-anaesthetic scoring system is described. The scoring system scores five parameters that may be quickly assessed by the recovery room staff at five-minute intervals. The system was usefully employed for a month's trial and has now been adopted on a full-time basis at this hospital.

Anesthesia, General↗

Evaluation of the transcutaneous electrical nerve stimulator for postoperative analgesia following cardiac surgery.

The effectiveness of transcutaneous electrical nerve stimulation (TENS) in postoperative pain relief was assessed in this prospective randomised controlled study of 31 patients during the first 72 hours after cardiac surgery. Fourteen patients were given functioning TENS units, and seventeen patients were given non-functioning units. Postoperative pulmonary function tests, analgesic requirements and the incidence of atelectasis were compared in the two groups. Morphine requirement was significantly reduced on the second postoperative day and peak expiratory flow rates (PEFR) were significantly improved for the first two postoperative days in patients with functioning TENS units. The forced vital capacity (FVC) was significantly larger with functioning TENS units on the second postoperative day, but there were no other significant differences in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) values between the two groups. A questionnaire given to patients assessing their opinions of the effectiveness of the TENS unit for analgesia showed a placebo effect in some patients with non-functioning units. In summary, this study suggests that TENS may be of benefit in postoperative pain relief after cardiac surgery, especially on the second postoperative day.

Adolescent↗

[Coronary involvement in Takayasu's disease. Apropos of 3 cases, of which 2 were surgically treated, and review of the literature].

Coronary arteries like other branches of the aorta may be involved in Takayasu's disease. This complication is not rare (7% of cases) but appears to be relatively unappreciated. Three new cases are reported of main coronary artery disease, two of which were treated by coronary bypass surgery. A review of the literature of 1 130 cases of Takayasu's disease revealed 86 cases with coronary involvement, 33 of which were confirmed anatomically and 15 by coronary arteriography. The clinical manifestations, angina and/or myocardial infarction, were present in 5% and 3% respectively, of patients with Takayasu's disease. They may be the first sign of the disease and, in some cases, the only symptomatic arterial localisation. The coronary lesions are either ostial, a direct complication of the aortic disease, or on a main vessel, usually proximal. Histological studies show typical changes of stenosing inflammatory panarteritis involving mainly the media and adventitia. Thrombosis and secondary atheromatous plaques may be observed. Aneurysms are rare. Apart from cases with typical ostial lesions, the coronary angiographic appearances are not specific, but some features are suggestive of the diagnosis; the occurrence in young women; the presence of associated peripheral arterial lesions, their localisation and grouping; their radiological and/or histological characteristics. The spontaneous prognosis of these proximal lesions is usually poor and justifies surgical revascularisation by coronary bypass. Six patients, including two in this series, have been treated surgically. The associated aortic lesions may pose special technical problems which we discussed. The relatively high incidence of coronary involvement in Takayasu's disease and its often unexpected revelation by myocardial infarction or sudden death, suggest that coronary arteriography should be undertaken more often during investigation of the arterial lesions of these patients. Takayasu's disease should figure prominently amongst the causes of coronary artery disease in young women.

Adolescent↗

[Aortic insufficiency in Takayasu's disease. Apropos of 3 surgically treated cases and review of the literature].

The author report the cases of three women with aortic regurgitation associated with aneurysmal dilatation of the ascending thoracic aorta. Aortic valve replacement was carried out in the 3 cases, with resection of the aortic aneurysm in 2 cases. Histological examination of the aortic wall in all 3 cases showed non-specific aortitis in the adventitia and media, appearances comparable to those described in Takayasu's disease. The incidence of aortic regurgitation in Takayasu's disease is about 10%. These 3 cases are compared with 30 other cases with histological confirmation in the medical literature, only 9 of which have undergone aortic valve replacement. The mechanism of the aortic regurgitation is analysed: dilatation of the aortic ring, inflammation of the valve cusps, commissural dysjunction or dilatation of the ascending aorta involving the line of commissural insertion. Aortic regurgitation is usually associated with other arterial localisations of the disease, but may also be found alone when the disease seems limited to the ascending aorta. Coronary artery disease, especially ostial, is observed in 30% of patients with this type of aortic regurgitation. Coronary angiography is therefore mandatory before surgery. The arterial involvement may be investigated initially and followed-up by 2 non-invasive investigations = digitalised intravenous angiography (DIVA) and M mode and 2D echocardiography. The two investigations give comparable results with regards to the study of the aorta, but the branches of the aorta and pulmonary arteries can only be investigated by DIVA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗