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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 505 records · Page 28Linked to original sources

Measurement issues in environmental epidemiology.

This paper deals with the area of environmental epidemiology involving measurement of exposure and dose, health outcomes, and important confounding and modifying variables (including genotype and psychosocial factors). Using examples, we illustrate strategies for increasing the accuracy of exposure and dose measurement that include dosimetry algorithms, pharmacokinetic models, biologic markers, and use of multiple measures. Some limitations of these methods are described and suggestions are made about where formal evaluation might be helpful. We go on to discuss methods for assessing the inaccuracies in exposure or dose measurements, including sensitivity analysis and validation studies. In relation to measurement of health outcomes, we discuss some definitional issues and cover, among other topics, biologic effect markers and other early indicators of disease. Because measurement error in covariates is also important, we consider the problems in measurement of common confounders and effect modifiers. Finally, we cite some general methodologic research needs.

Biomarkers↗

Physiological behaviour of encapsulated somatic embryos.

Somatic embryos are characterised by the absence of any protection, a very low reserve level and a high water content. The effects on the respiration and the radicular elongation of somatic embryos of a non toxic and easy to use hydrogel, such as alginate, have been studied. Respiration or germination rates decreased with an increase in alginate concentration. When the encapsulated somatic embryos were placed in a liquid medium, there was very little difference between the germination rates observed at different alginate concentrations, either with or without an additional PEI layer. The effect of capsule concentration on germination rate was significatively different when the artificial seeds were growing on solid media. Besides the anoxic treatment upon encapsulated somatic embryos, storage for one month also decreased the germination rate.

Alginates↗

[Cardiac and extracardiac abscesses in bacterial endocarditis].

Cardiac abscesses are observed in 20 to 30% of cases of infective endocarditis and in at least 60% of prosthetic valve endocarditis. The aortic valve ring is more frequently affected than the mitral valve ring. A cavity contiguous with a cardiac chamber forming a pseudo-aneurysm or a closed purulent collection, the abscess may extend to the neighbouring cardiac structures or to the ascending aorta. This extension may cause conduction defects, abnormal communications between the cardiac chambers, pericardial disease and, exceptionally, myocardial ischaemia, complications which are clinical signs of abscess formation in patients with infective endocarditis. The presence of a cardiac abscess is a poor prognostic factor in infective endocarditis. The diagnosis must be made at an early stage when surgical treatment is optimal. The most valuable investigation is transoesophageal echocardiography with a sensitivity of over 80% and a specificity of about 95%. This investigation has become practically routine in all patients with endocarditis in order to diagnose abscesses at an early stage, especially in cases of aortic or prosthetic valve endocarditis. Information about the site, size and extension of the abscess may be obtained and existing or potential complications may be envisaged with a view to surgery. Other imaging diagnostic techniques, such as angiography, CT scanning and nuclear magnetic resonance imaging have a number of disadvantages and are not more sensitive than transoesophageal echocardiography. Surgical techniques depend on the site and extension of the abscess. They are sutured or closed with dacron or pericardial patches after having been cleaned and filled with formulated resorcin glue. The valvular prosthesis is inserted either in anatomical position or in a sub or supracoronary dacron tube necessitated by the perivalvular extension of the infectious lesions. These complex procedures may require associated coronary reimplantation or revascularisation when the coronary ostia are affected. The highest operative mortality is observed in prosthetic valve endocarditis with abscess and extra-annular prosthetic implants. The risk of secondary valvular dehiscence, often recurrent, is much higher when there is an abscess at operation. Extracardiac abscesses in cases of infective endocarditis are mainly observed in the cerebral and/or splenic territories. They may become the main problem, especially cerebral abscesses, but they rarely require surgery.

Abscess↗

[Effects of ultrasound energy on femoral artery occlusion. Angiographic and angioscopic results].

Ultrasonic energy has been shown to be able to disrupt atherosclerotic plaques and thrombi. The authors used an ultrasonic angioplastic technique developed by the group in 10 patients with a femoral arterial occlusion. The ultrasonic angioplasty was attempted before surgical bypass using a 130 cm long titanium guide wire with a 0.8 mm diameter and a round distal tip measuring 2 or 2.5 mm. Angiographic and angioscopic examinations were performed before and after the procedure in 9 patients. It was not possible to perform the angioplasty in 1 patient. Angioscopy showed that the proximal part of the occlusion consisted of atheromatous material in 3 cases and of thrombus in 6 cases. Angiography showed complete restoration of flow in 4 cases; distal flow was very slow in 4 cases and no distal run-off was observed in 1 case. Angioscopy showed residual stenosis at the site of entry in only 1 case. In 3 cases, the artery had no significant residual stenosis. In the other 5 patients residual stenosis was present and angioscopy showed persistence of strands of fibrin and small thrombi. These results show that ultrasonic angioplasty was capable of recanalising an occlusion in 9 out of 10 patients with partial or total disruption of thrombi. At the present stage of development of this system, balloon angioplasty would be an essential complement in most cases in order to obtain normal flow without significant residual stenosis. The manoeuverability of the guide wire and the relatively small size of the round distal tip explain why not all the thrombi could be treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Effects of ultrasonic energy on blood clots in vitro].

Ultrasound may be used to dissolve arterial and venous thrombi. Its effects depends on the mode of ultrasonic vibration and on the length of the guide wire. The authors studied the in vitro effects of an ultrasonic angioplasty device coupled with a 130 cm long titanium flexible guide wire. The system comprises an automatic scanning function to determine the optimal frequency of resonance and works in the continuous mode of emission. Sixteen thrombi were studied of which 8 were acellular and 8 whole blood. In each group, 4 were treated in association with streptokinase and 4 by ultrasound alone. The ages of the thrombi in each subgroup were 1, 3, 7 and 15 days. All the thrombi were dissolved in 6 minutes or less (3'15" +/- 1'35") at an average optimal frequency of resonance of 19,444 Hz. Ninety six per cent of the debris had a diameter less than 10 microns. Less than 1% of the debris had a diameter larger than 100 microns. These large particles were observed in cellular thrombi and were almost completely absent in dissolved acellular thrombi. They were very fragile. The dissolution of the thrombi was not accelerated by the association of streptokinase. The ultrasonic energy did not induce D-dimer production and its action was probably due to cavitation. Ultrasonic energy could provide an alternative treatment for thrombotic vascular occlusion provided that more flexible guide wires could be designed.

Humans↗

[Neurohormonal profile in aortic valve stenosis].

The authors studied the responses of the main systems of sympathetic and hormonal regulation in valvular aortic stenosis, a special model of dissociation between arterial pressure and left ventricular function. The series comprised 14 patients with an average age of 70 +/- 9 years without diuretic therapy presenting with pure calcific aortic stenosis without other valvular or coronary disease. All were in sinus rhythm; 5 were taking an angiotensin converting enzyme inhibitor. Plasma concentrations of endothelin 1, atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, plasma renin activity (PRA), angiotensin II and aldosterone were measured in resting, fasting patients, by blood samplings from a peripheral vein immediately before cardiac catheterisation. The results were compared with the severity of the aortic stenosis (aortic valve area greater or less than 0.7 cm2), the ratio of left ventricular work/myocardial mass (greater or less than 0.6) and treatment (with or without ACE inhibitors). Catecholamine levels were much higher in severe aortic stenosis (noradrenaline: 579 +/- 66 pg/ml when valve surface area > 0.7 cm2 versus 900 +/- 92 pg/ml when valve surface area < 0.7 cm2; p < 0.01). Endothelin -1 and AVP concentrations were normal. Whereas PRA was normal, aldosterone levels were increased in patients without treatment by ACE inhibitors. This treatment did not, however, normalise the noradrenaline levels. The increase in ANF concentration was large when left ventricular work decreased with respect to myocardial mass (190.8 +/- 42.3 pg/ml if W/M was decreased versus 82.7 +/- 15.4 pg/ml when W/M was normal): this could be related to the degree of left ventricular hypertrophy.

Aged↗

Cyclophosphamide versus ifosfamide: a randomized phase II trial in adult soft-tissue sarcomas. The European Organization for Research and Treatment of Cancer [EORTC], Soft Tissue and Bone Sarcoma Group.

Ifosfamide (5 g/m2) was compared with its parent analogue cyclophosphamide (1.5 g/m2) in a randomized phase II study. Both drugs were given by 24-h intravenous (i.v.) infusion every 3 weeks along with i.v. bolus infusions of mesna (400 mg/m2), which was given every 4 h for nine administrations. Eligibility criteria included an age of 15-75 years, biopsy-proven advanced metastatic soft-tissue sarcoma, and a World Health Organization performance status of 0-2. Exclusion criteria were prior treatment with classic alkylating agents, a creatinine level of > 150 mumol/l, a bilirubin level of > 20 mumol/l, a leukocyte cell count of < 3.5 x 10(9)/l, and a platelet count of < 100 x 10(9)/l. A total of 171 patients were entered, 24 of whom were ineligible and 12, inevaluable, leaving 135 patients evaluable. In all, 67 patients were treated with cyclophosphamide, and the overall response rate was 7.5%. All responders to cyclophosphamide were patients who had not received prior chemotherapy (13% of 38 patients). Another 68 patients were given ifosfamide, 18% of whom responded to treatment. Of the 28 ifosfamide-treated patients who had received prior chemotherapy, 7% were responders. The response rate for the remaining 40 patients was 25%. The higher overall response rate (P = 0.13) obtained with less myelosuppression in ifosfamide-treated patients suggests that this agent may have advantages over cyclophosphamide in combination therapy.

Adolescent↗

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft-tissue sarcoma.

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft-tissue sarcoma. Treatment consisted of an intravenous bolus injection of doxorubicin at a dose of 50 mg/m2 followed by a 24-h infusion of ifosfamide at 5 g/m2 plus mesna, with therapy being repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of the 203 patients entered, 175 were evaluable for response. The overall response rate was 35% (95% confidence interval, 28%-42%), with 9% of patients achieving complete responses and 26% showing partial responses. The median time to progression was 29 weeks for all evaluable patients and 67, 40, and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (World Health Organization grades 3 and 4) in 73% of the evaluable patients. Other side effects were rare and usually well manageable.

Adolescent↗

Gastric intramucosal acidosis in patients with chronic kidney failure.

BACKGROUND: Patients with chronic kidney failure have an increased incidence of gastrointestinal complications, particularly bleeding from the stomach. Diminished mucosal blood flow is thought to be an important etiologic factor for such bleeding. METHODS: Eleven patients with kidney failure on maintenance dialysis underwent placement of a gastric tonometer for the determination of gastric intramucosal pH (pHi) before and during dialysis. The arterial pH (pHa), calculated pHi, and pHa-pHi differences were compared with the results in a control group of seven normal volunteers. RESULTS: The patients with chronic kidney failure had a mean (+/- SD) pHa (7.36 +/- 0.04) similar to that found in seven control subjects (7.37 +/- 0.04). However, the gastric mucosal pH in the patients on dialysis (7.20 +/- 0.17) was lower than in the seven control subjects (7.38 +/- 0.06) (p < 0.01). A gastric mucosal pH thought to be predictive of either bleeding from stress ulceration (pHi < 7.32) or mucosal ischemia (pHi-pHa difference > 0.13) was found in nine (82%) of the patients with kidney failure and in only one (14%) of the control subjects (p < 0.001). CONCLUSIONS: This new preliminary finding suggests that the high incidence of gastric bleeding in chronic kidney failure may be related to mucosal ischemia.

Acidosis↗

Isolation and characterization of two opioid peptides from a bovine hemoglobin peptic hydrolysate.

Two opioid peptides were isolated from a bovine hemoglobin hydrolysate, by use of gel permeation (GP) and reverse phase (RP) high performance liquid chromatography (HPLC). Their primary structure and accurate molecular weights, determined by amino acid analysis and fast atom bombardment (FAB) mass spectrometry, were identical to fragments 31-40 (LVV-hemorphin-7) and 32-40 (VV-hemorphin 7) of the beta-chain of bovine hemoglobin. The same fragments occur in human hemoglobin in positions 32-41 and 33-41 of the beta-chain, respectively. The opioid potency of these peptides, exhibited by use of electrically stimulated muscle of isolated guinea-pig ileum (GPI), were significant and comparable with some others previously described. In addition, the location of the two opioid peptides, VV-hemorphin-7 and LVV-hemorphin-7, revealed the existence of a "strategic zone" both in the bovine and human beta-chains of hemoglobin.

Amino Acid Sequence↗

Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts.

A cDNA encoding the dihydroorotate dehydrogenase (DHOdehase; EC 1.3.3.1) of the yeast Schizosaccharomyces pombe was isolated by functional complementation in Saccharomyces cerevisiae. A divergent subcellular compartmentation of the DHOdehase of each yeast was shown. The DHOdehase from Sch. pombe was localized in the mitochondria whereas its homolog from S. cerevisiae was found to be cytosolic. The heterologous expression of the Sch. pombe enzyme in S. cerevisiae allowed us to demonstrate that the Sch. pombe DHOdehase activity requires the integrity of the mitochondrial electron transport chain. Indeed, the presence of a mutation inactivating cytochrome b abolished the complementation of a S. cerevisiae ura1 mutant by the corresponding Sch. pombe gene. By contrast, in vitro studies have revealed that the DHOdehase of S. cerevisiae uses fumarate as terminal electron acceptor. These results are discussed in relation to the anaerobic growth competence of the two yeasts and to the fermentative processes they use.

Aerobiosis↗

Isolation and characterization of a bradykinin-potentiating peptide from a bovine peptic hemoglobin hydrolysate.

A bradykinin potentiating peptide was isolated from a peptic bovine hemoglobin hydrolysate, by the use of reversed-phase high-performance liquid chromatography (RP-HPLC). Its primary structure, determined by fast atom bombardment (FAB) and tandem mass spectrometry (MS/MS), was identical to fragment 129-134 of the alpha-chain of bovine hemoglobin. The bradykinin potency of this peptide, as exhibited by the guinea-pig ileum contraction, was significant and comparable with some others previously described.

Amino Acid Sequence↗