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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 865 records · Page 48Linked to original sources
PubMed1983

Multiple steady states and oscillatory behavior of a compartmentalized phosphofructokinase system.

This paper discusses interacting diffusion and reaction in an open enzyme system. The enzyme, rabbit muscle phosphofructokinase (PFK; ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11), is inhibited strongly by excess of the substrate ATP. Metabolites diffuse through an inert membrane separating the enzyme from the bulk reacting medium. We demonstrate that such a simple system is able to account for the existence of both oscillatory behavior (limit cycle) and multiple steady states (hysteresis) as well as for the sudden transitions between stable and periodic behaviors. Experimental evidence for time oscillations is given.

Adenosine Triphosphate↗
PubMed1983

[Long-term treatment of chronic heart failure by an inhibitor of angiotensin converting enzyme].

We studied the hemodynamic, echocardiographic, phonomechanographic and hormonal changes during acute (25 mg) and chronic (6 months--75 to 225 mg/day) treatment of 10 patients with congestive cardiac failure due to cardiomyopathy with dilatation with SQ 14 225 (Captopril). The following changes were observed after the single dose: an increase in cardiac output (p less than 0,001), in stroke volume (p less than 0,01), a reduction in heart rate (p less than 0,01), in peripheral resistance (p less than 0,001) and pulmonary capillary pressure (p less than 0,001). There were no significant changes in end systolic or end diastolic left ventricular internal diameter. Plasma renin activity increased (p less than 0,001); there was a concurrent fall in serum aldosterone (NS): the plasma concentration of converting enzyme decreased (p less than 0,001). There was a correlation between the increase in peripheral resistance under basal conditions and the basal plasma renin activity (R = 0,72, p less than 0,02). The decrease in peripheral resistance after captopril also correlated with basal plasma renin activity (R = 0,89, p less than 0,01). After six months continuous therapy, the hemodynamic effect was sustained and was accompanied by a significant symptomatic improvement. Left ventricular internal end systolic and end diastolic diameters decreased (p less than 0,01 and p less than 0,01 respectively). The pre-ejectional period decreased (p less than 0,05). Serum aldosterone fell significantly (p less than 0,001) as did plasma renin activity (p less than 0,01); the serum level of converting enzyme remained low with respect to its initial value. These results show that captopril may be useful in severe cardiac failure without tolerance during long-term administration. No renal or hematological toxicity was observed in this group of patients.

Adult↗
PubMed1983

[Treatment of peritonitis in peritoneal dialysis. Comparison between continuous lavage with a machine and intermittent lavage with 4 CAPD bags/day].

Since 1978, 54 episodes of PT occurred in patients treated by PD, first 26 PT (group A) were treated by CLM (40 l/day) and in situ antibiotics (AB): in the absence of Candida, the association of sulfamethoxazol (SMZ: 80 mg/l) and trimethoprime (TMP: 16 mg/l) was used. Only when a Candida was present amphotericine B (AMB: 5 mg/l) was used. CLM was continued until PT was cured. The last 29 PT (group B) were treated by 4 bags/day of CAPD with in situ AB: SMZ: 200 mg/l and TMP 40 mg/l and a systematic oral prophylaxis of Candida was performed by AMB 1,5 g/day. In group A, 5 patients died and 2 others in group B. Complications were more frequent in group A (14) than in group B (6): p less than 0.02. In group A, the AB was changed in 7 cases because of initial resistance (1) or bacterial superinfection (2) or Candida superinfection (4). In group B, AB was changed in 9 cases because of initial resistance (7) or Candida superinfection (2). In conclusion the treatment of PT by 4 bags per day with in situ AB cure PT as rapidly as CLM in spite of lower doses of SMZ - TMP. However, this method is easier to perform and give less complication than CLM. It must be the treatment of choice of PT from peritoneal dialysis.

Anti-Bacterial Agents↗
PubMed1982

Variability of static visual threshold responses in patients with elevated IOPs.

We determined the static visual thresholds within 15 degrees of fixation of 36 patients with elevated intraocular pressures but normal visual fields and compared the result with 36 controls matched for age and sex. We found no difference in the mean threshold level between the two groups. We did find a tendency for the patients with elevated IOPs to have greater variability or scatter of their threshold responses close to fixation. We also found the patients had larger cup to disc ratios than the controls.

Humans↗
PubMed1982

Evaluation of the peak frequency ratio (PFR) measurement in the detection of internal carotid artery stenosis.

The peak frequency ratio (PFR) between the internal carotid and common carotid artery Fast Fourier Transform Spectral Analysis patterns has been used to identify patients with internal carotid artery stenosis. To evaluate further the accuracy of the PFR, we applied it to the spectral analysis data from 396 vessels whose sound signals were obtained with a Duplex scanner (pulsed Doppler) and 246 arteries whose audible flow data were generated by a continuous-wave Doppler. The pulse Doppler with spectral analysis (PD/SA) correctly identified 221/254 (87%) of the vessels with less than 50% angiographic stenosis, 81/100 (81%) of the arteries with 50-99% stenosis, and 35/42 (83%) of the totally occluded internal carotid vessels for an overall accuracy of 85%. The continuous-wave Doppler with spectral analysis (CW/SA) did well in two categories but had an unacceptably high 47% false-negative rate for arteries with 50-99% stenosis. The PFR when applied to PD/SA test results is a useful parameter in screening patients with suspected internal carotid artery stenosis.

Arterial Occlusive Diseases↗
PubMed1982

Steroid modifications with immobilized biocatalysts--use of immobilized enzyme-requiring cofactor regeneration and of immobilized mycelium.

Two biological approaches have been investigated for specific modifications of steroids. The first one uses the purified enzyme for the specific dehydrogenation of androsterone to androstanedione. The enzyme used is 3 alpha-hydroxysteroid dehydrogenase which requires a cofactor (NAD). A cofactor regeneration is needed so that the process could work continuously. The conjugation of two points (immobilization of the enzyme and optimization of the ratio methanol-water) allows a continuous work of the enzyme during 25 days. Moreover, we propose a chemical regeneration of the cofactor using methoxy derivative of phenazine methosulphate. Right now it is the limiting step of the process. The second approach of steroid modification uses a whole mycelium of Aspergillus phoenicis for the specific hydroxylation of progesterone to 11 alpha-hydroxy progesterone. The transformation of 90% of the progesterone is obtained with calcium alginate immobilization and the lowest number of products is obtained at pH lower than 2.5 with carrageenan and polyurethane immobilization. It seems promising to apply immobilized biocatalysts to the bioconversion of hydrophobic compounds in organic solvents system.

3-Hydroxysteroid Dehydrogenases↗
PubMed1982

N-(phosphonacetyl)-L-aspartate (PALA) in advanced soft tissue sarcoma: a phase II trial of the EORTC soft tissue sarcoma group.

Thirty-six patients with measurable or evaluable advanced soft tissue sarcoma were entered in a phase II trial with PALA. Among the 27 evaluable patients, 15 were men, the median age was 55 yr (16-69) and the median performance status (Karnofsky) was 80 (50-100). Most patients had leiomyosarcoma (8), liposarcoma (3), neurofibrosarcoma (3), synovial cell sarcoma (3), or undifferentiated sarcoma (3). Indicator lesions consisted essentially of lung metastases (21) and/or soft tissue lesions (14). All patients had received prior chemotherapy with 1-5 regimens and 6 had achieved objective response with these previous treatments. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-17) were administered. Partial remission (greater than 50%) was obtained in one patient with a liposarcoma who had also responded to prior combination chemotherapy. This single response to PALA lasted 6 weeks from initiation of therapy. Four patients had unchanged disease after 6+ courses of PALA and 22 had progressive disease. Toxic effects were generally mild to moderate and included cutaneous toxicity (17), diarrhea (14), stomatitis (13), ocular manifestations, consisting of conjunctivitis, corneal ulceration and/or photophobia (11), nausea and vomiting (6) and, possibly, seizures (2). There was no evidence of drug-related myelosuppression. It is concluded that PALA given at the dose schedule selected for this trial has no significant antitumor activity in advanced soft tissue sarcoma previously treated with chemotherapy.

Adolescent↗
PubMed1982

N-(phosphonacetyl)-L-aspartate (PALA) in advanced malignant melanoma: a phase II trial of the EORTC Malignant Melanoma Cooperative Group.

Thirty-nine patients with measurable advanced malignant melanoma were entered in a phase II trial with PALA. Among the 36 evaluable patients there were 18 men and 18 women, with a median age of 53 yr (29-73) and a median performance status (Karnofsky) of 100 (50-100). Indicator lesion consisted essentially of soft tissue lesions (29 patients) and/or lung metastases (9 patients). Only three patients had received prior chemotherapy. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-8) were administered. Partial response (greater than 50%) was obtained in 4 patients for 6-17 weeks. Eight patients had stable disease after 3 courses of PALA and 24 had progressive disease. Toxic effects were generally mild to moderate and mainly included cutaneous toxicity, nausea and vomiting, stomatitis, and diarrhea. Myelosuppression was rare and negligible. It is concluded that PALA given at the dose schedule selected for this trial is fairly well tolerated and has borderline antitumor activity in good-risk patients with advanced malignant melanoma.

Adult↗
PubMed1982

Cisplatin and vindesine combination chemotherapy in advanced malignant melanoma: an EORTC phase II study.

Sixty-one evaluable patients with measurable advanced malignant melanoma received 4-week courses of a combination of cisplatin 100 mg/m2 as a 24-hr i.v. infusion on day 1 and vindesine 3 mg/m2 as an i.v. bolus on days 1, 8, 15 for two courses and every other week thereafter. Two patients achieved complete response for 46 and 81+ weeks respectively, eleven patients achieved partial response for a median of 17 weeks (range 8-26) and three patients had no change for 24 weeks or more. The overall response rate of 21% did not seem to be affected by prior chemotherapy or site of indicator lesions, soft tissue vs visceral. Myelosuppression, consisting essentially of leucopenia, required dose schedule modifications in 41% of the first two courses and 12% of the remaining courses, but never produced major complications. Non-hematologic toxic effects were prominent, especially nausea and vomiting, which were universal. Alopecia was seen in 71% of the patients, neuromuscular manifestations in 39%, diarrhea in 30%, renal impairment in 25%, mucositis in 12%, ototoxicity in 7% and phlebitis in 3%. These results do not suggest striking additive or synergistic antitumor activity of cisplatin and vindesine in advanced malignant melanoma, at least with the method of drug administration selected for this trial.

Adult↗
PubMed1982

Electrical excitability of artificial enzyme membranes. I. Ion-exchange properties of synthetic proteinic films.

This paper deals with the physico-chemical properties of artificial membranes. The membranes are produced with different protein molecules which offer amphoteric sites with weakly ionizable groups. The adsorption of phosphate and sodium ions in different artificial proteinic membranes is studied as a function of both pH and concentration of the external solution. The influence of the sign and density of fixed charges as the nature and concentration of mobile ions is studied by measuring the potential difference between both membrane compartments.

Acetylcholine↗
PubMed1982

Electrical excitability of artificial enzyme membranes. II. Electrochemical and enzyme properties of immobilized acetylcholinesterase membranes.

This paper deals with aspects of the reciprocal interaction between enzyme activity and the microenvironment or the potential difference in artificial proteinaceous membranes bearing cross-linked acetylcholinesterase. The potential difference resulting from asymmetric substrate injection into the system is recorded as a function of time. The influence of the membrane charge density on both enzyme activity and potential difference is studied by varying the external solution pH. The enzyme specific potential is initiated by local change of pH at the membrane level and the dependence on the buffer strength is studied. The recorded potential difference appears to be the result of the reciprocal interaction between enzyme reaction and the diffusion of substrate or products.

Acetylcholinesterase↗