Biomedical subjects

C Lucas

Publications and source records attributed to C Lucas.

At least 91 records · Page 5Linked to original sources

PubMed1998

Impact of ethnicity on left ventricular mass and relative wall thickness in essential hypertension.

This study was designed to evaluate the impact of ethnicity on left ventricular (LV) mass, and relative wall thickness in 527 patients (57% men, mean age 60 +/- 7 years) with mild to moderate high blood pressure. There were 63% Caucasians, 21% African-Americans, and 16% Hispanics. LV mass was indexed according to body surface area, height, and height to the allometric power of 2.7. Relative wall thickness included the 4 widely recognized patterns: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. LV mass indexed to body surface area was similar among all 3 ethnic groups (Caucasians 117.1 g/m2, African-Americans 119.2 g/m2, Hispanics 122.7 g/m2); however, when indexed to height and height to the power of 2.7, Hispanics had slightly larger masses than the other 2 groups (Hispanics 168.1 and 73.3 g/m2.7 vs Caucasians 159.8 and 64.4 g/m2.7 [p = NS and p < 0.005]; and vs African-Americans 164.8 and 69.2 g/m2.7 [p = NS for both]). Using body surface area, the concentric remodeling was the predominant form of cardiac adaptation in Caucasians (36%) and African-Americans (42%), whereas the concentric hypertrophy pattern was 38% in Hispanics. Using indexing for both height and height to the power of 2.7, the concentric hypertrophy pattern predominated in all 3 ethnic groups (Caucasians 48% and 51%; African-Americans 68% and 66%; Hispanics 59% and 65%). In conclusion, because of the independent impact of weight on high blood pressure, LV mass adjusted to height or to height at the power of 2.7 should be reported in population studies. The concentric hypertrophy pattern--classic LV response to pressure overload conditions--is better represented when LV mass is indexed to height or to height to the allometric power of 2.7 than to body surface area.

Aged↗

PubMed1998

Phase I clinical and pharmacokinetic study of S9788, a new multidrug-resistance reversal agent given alone and in combination with doxorubicin to patients with advanced solid tumors.

PURPOSE: The objectives of this phase I study were to evaluate the toxic effects and the maximum tolerated dose (MTD) of S9788, a new modifier of multidrug resistance (MDR), when given alone and in combination with doxorubicin to patients with advanced solid tumors; to achieve a potentially active plasma concentration of S9788; and to study the pharmacokinetics of both drugs. METHODS: A total of 26 patients (median age 58 years) entered the study. S9788 was given alone as a 30-min infusion at day 1 and in combination with a 50-mg/m2 bolus of doxorubicin at days 8 and 29. Dose levels of S9788 were escalated from 8 to 96 mg/m2 according to the modified Fibonacci scheme. Plasma samples were taken predose as well as during and up to 48 h after the beginning of infusion for S9788 and doxorubicin quantitation. Fractionated urine samples were also collected for up to 24 h for S9788 determination. RESULTS: The dose-limiting side effects of S9788 consisted of bradycardia, sometimes associated with faintness or dizziness. The MTD of S9788 was 96 mg/m2. No enhancement of doxorubicin toxicity was observed. One partial response (duration 140 days) was observed at 96 mg/m2 in a patient with multiple lung metastases from a refractory urothelial carcinoma. Pharmacokinetic studies were performed in 24 patients. Since the mean apparent elimination half-life of S9788 was 46 +/- 23 h and the last plasma sampling time was 48 h, only model-independent parameters were considered. Plasma levels of S9788 were below the limit of quantitation (4 x 10[-3] microM) before each drug administration. S9788 plasma levels of up to 3.7 microM could be obtained with this administration schedule. The urinary elimination of the unchanged drug was negligible, whatever the collection period. In spite of the large inter- and intraindividual variability, plasma pharmacokinetics of S9788 given as a 30-min i.v. infusion were linear up to 96 mg/m2 and were not modified by doxorubicin administration. Doxorubicin pharmacokinetic parameters did not seem to be influenced by S9788 coadministration. CONCLUSION: The dose-limiting toxicity of S9788 consisted of bradycardia or clinical symptoms suggesting a vasovagal impact such as faintness or dizziness. The MTD of S9788 was 96 mg/m2. The pharmacokinetic parameters of doxorubicin in this study were close to those usually described and were not influenced by escalation of the S9788 dose. No pharmacokinetic interaction was observed between S9788 and doxorubicin. The clinical tolerability of the combined treatment is in good agreement with the pharmacokinetic findings, since no enhancement of doxorubicin toxicity was observed.

Adult↗

PubMed1998

[Brain stem metastasis revealing bronchopulmonary cancer: 2 cases].

INTRODUCTION: Brainstem metastasis is a very rare revealing feature of lung carcinoma. EXEGESIS: We report two cases of brainstem metastasis revealing lung carcinoma. In the first case, diagnosis was made on stereotaxic biopsy. In the second, the biopsy was not necessary as lung lesion was observed on thoracic CT-scan. Diagnosis of metastasis is difficult when a brainstem tumor occurs. CONCLUSION: Stereotaxic biopsy is an interesting tool to distinguish between primary lesion and metastasis, but only when diagnosis work-up of primary cancer is negative.

Adenocarcinoma↗

PubMed1998

Phase I pharmacological study of intra-arterially infused fotemustine for colorectal liver metastases.

Fotemustine was investigated in 17 patients with progressive hepatic metastases from colorectal carcinoma to define the maximally tolerated dose for a daily hepatic intra-arterial infusion (HAI) schedule. Haematotoxicity was delayed, dose-dependent and related to pretreatment, with thrombo- and leucocytopenia being dose-limiting. Local side-effects at the liver were mild. Infection (WHO grade III) occurred in 1 patient due to neutropenia. Other side-effects, particularly renal, pulmonal, neurological or cardiac toxicity, mucositis and diarrhoea, hair loss or allergic reactions did not occur. Pharmacokinetic analysis indicated a short plasma half-life (t1/2 = 25.8 +/- 11.5 min) and a high body clearance (CL = 2193 +/- 870 ml/min) with large inter- and intra-individual variations. Of 15 evaluable patients, one complete and three partial responses were observed (ORR = 27%; CI95% [4.5-49.5%]). All tumour remissions appeared at higher dose levels in previously untreated patients. Considering the absence of mucosal side-effects, such as mucositis/diarrhoea and of hepatic toxicity, this agent was well tolerated. The recommended intra-arterial dose for consecutive phase II trials is 125 mg/m2/day1-3.

Adolescent↗

PubMed1998

Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma.

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.

Adolescent↗

PubMed1998

Antithrombin, protein C and protein S levels in 127 consecutive young adults with ischemic stroke.

OBJECTIVES: The aim of our study was to evaluate the prevalence of antithrombin, protein C and protein S deficiencies in consecutive ischemic stroke patients under 45. MATERIAL AND METHODS: We studied 127 consecutive patients with a mean age of 34.4 years admitted for an ischemic stroke, over a 2-year period, after exclusion of those with arterial dissection. Antithrombin, protein C and protein S levels were measured in all patients at the acute stage of the ischemic stroke and measurements were repeated in case of abnormality. RESULTS: We found abnormal levels in 9 patients. Seven had an acquired cause of deficiency (pregnancy, oestrogen, acute inflammation). Two had no obvious acquired cause of deficiency but further controls were normal. CONCLUSIONS: Hereditary deficiencies of coagulation inhibitors are rare in ischemic stroke patients under 45 and their systematic detection seems to be of poor interest.

Adolescent↗

PubMed1998

Stroke patterns of internal carotid artery dissection in 40 patients.

BACKGROUND AND PURPOSE: Internal carotid artery dissection (ICAD) is a frequent cause of ischemic stroke in young patients. Whether cerebral ischemia is of embolic or hemodynamic origin remains to be determined. Heparin is often administered in ICAD; however, a drug trial can hardly be conducted because of the low recurrence rate after the acute stage. Therefore, the best therapeutic approach should be determined on the basis of the presumed mechanism of cerebral ischemia. One way to approach the mechanism of stroke in ICAD is to determine stroke patterns. We postulated that most cortical and large subcortical infarcts (>/=15 mm) are of embolic origin and that small subcortical infarcts (<15 mm) and junctional infarcts are not. The aim of our study was to determine the stroke patterns in 40 consecutive patients with ICAD. METHODS: The patients (26 women and 14 men; mean age, 42.8 years) had a total of 65 ICADs. Seventeen patients were free of any vascular risk factor. CT scans, MRI scans, and angiographic features were analyzed by observers who were blinded to the clinical findings. RESULTS: We found 34 cortical infarcts, 25 large subcortical infarcts, 1 small subcortical infarct, and 5 junctional infarcts. CONCLUSIONS: Most infarcts related to ICAD are cortical infarcts or large subcortical infarcts; small subcortical infarcts and junctional infarcts are infrequent. Therefore, these findings suggest that most infarcts occurring in carotid artery dissection (CAD) are probably embolic rather than hemodynamic in origin. According to this presumed mechanism, anticoagulation seems a logical treatment at the early stage of CAD.

Adolescent↗

PubMed1998

Methicillin-resistant Staphylococcus aureus infection in palliative care.

Our objective was to assess the impact of methicillin-resistant Staphylococcus aureus (MRSA) infection in palliative care. The study was conducted at three hospices in south London, totalling 118 beds, and the following two methods were used. Firstly, a retrospective review of the notes of patients who were known to be MRSA positive at admission or were subsequently found to be MRSA positive was taken. Secondly, a prospective study of factors influencing bed occupancy in one hospice was conducted. The proportion of admissions who were MRSA positive ranged from 4% to 8% in the three hospices. Seven of the 43 patients who had MRSA suffered clinically significant infections. Risk factors for colonization and bacteraemia were similar to the general population. Sites of infection were variable and multiple and treatment regimes for eradication were variable, with varying outcomes. MRSA infection appeared to delay admission because of the need for single rooms, of which there are few Time spent cleaning rooms after discharge or death also reduced the number of available beds. It was concluded that MRSA infection is associated with significant morbidity in a small number of palliative care patients. Beds unavailable because of MRSA should be considered in bed occupancy figures, otherwise bed occupancy may appear artificially low. The psychological and financial impact of the infection in palliative care patients needs further evaluation.

Adult↗

PubMed1998

Variation in the management of dysphagia after stroke: does SLT make a difference?

Dysphagia is a frequent consequence of acute stroke. Previous studies have demonstrated better clinical outcomes for patients managed by dysphagia teams, which have always included a speech and language therapist (SLT). This study compares dysphagia management for stroke patients in two hospitals with differing involvement of SLTs in dysphagia services. There was a trend towards better identification of dysphagia, more complete documentation of nutrition and hydration management, less risky dysphagia management and less perceived need for chest physiotherapy at the hospital with locally-based SLT provision, compared with the hospital with extra-contractual referral (ECR) for SLT dysphagia assessment. The specific contribution of the SLT in the dysphagia team is discussed.

Adult↗

PubMed1998

Short report: detection of Leishmaniavirus in human biopsy samples of leishmaniasis from Peru.

Leishmaniavirus is a double-stranded RNA virus that persistently infects some strains of the protozoan parasite Leishmania. There is considerable interest in the possibility that the presence of this virus alters parasite phenotype and may affect disease pathogenesis. If so, the virus marker could provide a valuable prognostic indicator for human leishmaniasis, particularly in those cases caused by New World parasite strains. The virus has been detected in cultured L. braziliensis, L. b. guyanensis, and L. major. To date there has been no information as to the extent of infection in samples prior to culturing in the laboratory. This study demonstrates, through the reverse transcription-polymerase chain reaction, that Leishmaniavirus exists in human biopsy samples of leishmaniasis prior to manipulation in culture.

Animals↗

PubMed1998

Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Purified rabbit immunoglobulin raised against yeast-expressed recombinant FVO or 3D7 Plasmodium falciparum merozoite surface protein-1 (MSP-1) 19k-D C terminal fragment (MSP-1(19)) was transfused into malaria-naive Aotus nancymai monkeys that were immediately challenged with FVO asexual stage malaria parasites. Control monkeys received rabbit immunoglobulin raised against the sexual stage antigen Pfs25 or Aotus hyperimmune serum obtained from monkeys immunized by P. falciparum infection and drug cure. Passive transfer of rabbit anti-MSP-1(19) failed to protect against homologous or heterologous challenge and, when compared with negative controls, there were no differences in prepatent periods or time to treatment. Interestingly, rabbit anti-MSP-1(19), but not anti-Pfs25, immunoglobulin, and immune monkey serum prevented the development of antibodies directed against MSP-1(19) fragment by infected monkeys, indicating that the antibodies were reactive with native MSP-1(19) antigen in vivo. The prepatent period and time to treatment was greatly delayed in the two monkeys that received Aotus immune serum, both of which developed a chronic intermittent low level infection. In vitro parasite growth inhibition assays (GIAs) confirmed the presence of inhibitory activity (40% maximum inhibition) in concentrated anti-MSP-1(19) immunoglobulin (4.8 mg/ml), but the peak concentrations we achieved in vivo (1 mg/ml) were not inhibitory in vitro. Subinhibitory levels of anti-MSP-1(19) antibodies achieved by passive transfer were not protective against P. falciparum challenge.

Animals↗

PubMed1998

Helical CT for the follow-up of cervical internal carotid artery dissections.

PURPOSE: The aim of this study was to assess the changes over time of internal carotid artery (ICA) dissections by using helical CT. METHODS: Twenty-seven patients with 30 angiographically proved ICA dissections were followed up with helical CT at 7 to 62 months (median, 24 months) after conventional angiography. CT scans, analyzed independently by two radiologists in a blinded fashion, were evaluated for the presence of mural thickening, aneurysmal formation, and arterial occlusion. In cases without persisting occlusion or aneurysm, we measured the external diameter of the ICA at its upper segment. RESULTS: The interobserver agreement was good. Mild mural thickening was observed in four cases of 30 previously dissected ICAs. All stenotic and nearly occlusive dissections without an aneurysm (n = 12) reverted to a normal or nearly normal diameter. Half the aneurysms resolved spontaneously (four of eight). Of the 10 occluded ICAs, nine were recanalized, but their external diameter was significantly smaller than that of normal carotid arteries, and a hypoplastic appearance was seen throughout the cervical segment of the ICA in three cases. CONCLUSION: Most arterial lesions tend to improve or disappear spontaneously, but persisting ICA narrowing may be observed in the late course of occlusive-type dissections.

Adult↗

PubMed1998

Contrast-enhanced three-dimensional fast imaging with steady-state precession (FISP) MR angiography of supraaortic vessels: preliminary results.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the effectiveness of contrast-enhanced fast three-dimensional (3D) MR angiography in depicting both the carotid and vertebral arteries in their cervical portions and to compare MR angiography with conventional angiography for the evaluation of arteriosclerotic disease. METHODS: Twenty-seven patients with ischemic cerebral events in the anterior (n = 18) and posterior (n = 9) circulation underwent contrast-enhanced 3D MR angiography in the coronal plane. MR angiograms were examined in a blinded fashion by two observers independently. Stenosis was classified according to the appearance of the residual lumen (no stenosis, mild stenosis, moderate stenosis, severe stenosis, occlusion). Conventional angiography was used as the standard of reference. RESULTS: Proximal great vessels and carotid siphons were not assessable on MR angiograms in 35% of cases owing to limited coverage. All cervical and petrous segments of the internal carotid arteries (ICAs) and 93% of the extracranial vertebral arteries were assessable. Flow-related artifacts were observed in seven cases of severe stenosis, including three with signal void at the site of narrowing and four with signal loss in the distal ICA. Interobserver agreement was good and significant. Overall agreement between 3D MR angiography and conventional angiography was good for the anterior and posterior circulations despite a tendency toward overestimation of stenoses on MR angiograms. Clinically relevant stenoses and occlusions were correctly identified on 3D MR angiograms, providing good sensitivity and specificity. CONCLUSION: Contrast-enhanced 3D MR angiography is a promising tool for assessing arteriosclerotic lesions of supraaortic vessels. Further studies with larger groups are required to determine its value for patient care.

Adult↗

PubMed1997

Contribution to the physiological characterization of glycerol active uptake in Saccharomyces cerevisiae.

Evidence is presented here that in Saccharomyces cerevisiae IGC 3507, grown either on glycerol, ethanol or acetate, glycerol is transported by a high affinity uptake system of the electrogenic proton symport type, with Km of 1.7 +/- 0.7 mM, Vmax 441 +/- 19 micromolh(-1) g(-1) dry weight and a stoichiometry of 1:1 proton per molecule of glycerol, at 30 degrees C and pH 5.0. No competitors were found among other polyols and sugars. Glycerol maximum accumulation ratios followed p.m.f. with extracellular pH. CCCP prevented glycerol accumulation, and inhibited uptake. NaCl did not interfere with H+/glycerol kinetics and energetics. This transport system was shown to be under glucose repression and inactivation. Glucose-grown cells presented, instead, a lower affinity permease for glycerol, probably a facilitated diffusion. Growth on glucose in the presence of NaCl did not induce the high affinity carrier. The stringent control of cell physiological condition over induction suggests for glycerol proton symport rather a physiological role connected with growth under gluconeogenic conditions.

Biological Transport, Active↗

PubMed1997

Comparison of left ventricular mass and geometric remodeling in treated and untreated men and women >50 years of age with systemic hypertension.

To investigate the effects of left ventricular (LV) mass and geometry in hypertensive patients >50 years of age, 540 men and women were divided into controlled, uncontrolled, and untreated groups. The high prevalence of concentric LV hypertrophy in postmenopausal women, despite medical therapy, emerged as a potentially important and underrecognized factor of their cardiovascular risk.

Aged↗

PubMed1997

Disparity between diastolic mitral flow characteristics and left ventricular mass in essential hypertension.

Because left ventricular (LV) hypertrophy and aging have been associated with abnormal LV relaxation, this study evaluated the impact of LV mass on the filling patterns derived by Doppler in a large population aged > or =50 years. Results suggest that in essential hypertension the intrinsic myocardial composition is more important than cardiac hypertrophy in determining LV diastolic properties. This apparent discrepancy between LV mass and diastolic filling patterns highlights the difficulty in establishing the diagnosis of diastolic dysfunction in elderly hypertensives.

Aged↗

PubMed1997

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer.

S9788 is a new triazineaminopiperidine derivate capable of reversing multidrug resistance (MDR) in cells resistant to chemotherapeutic agents such as doxorubicin. It does not belong to a known class of MDR revertants, but its action involves the binding of P-glycoprotein. Thirty-eight evaluable patients with advanced colorectal or renal cell cancer were treated with doxorubicin alone (16 patients) followed after disease progression with combination treatment of doxorubicin plus S9788 (12 patients) or upfront with the combination of doxorubicin plus S9788 (22 patients). S9788 was given i.v. as a loading dose of 56 mg m-2 over 30 min followed by doxorubicin given at 50 mg m-2 as a bolus infusion. Thereafter, a 2-h infusion of S9788 was administered at escalating doses ranging from 24 to 120 mg m-2 in subsequent cohorts of 4-10 patients. Pharmacokinetic analysis demonstrated that concentrations of S9788 that are known to reverse MDR in vitro were achieved in patients at non-toxic doses. Compared with treatment with doxorubicin alone, treatment with the combination of doxorubicin and S9788 produced a significant increase in the occurrence of WHO grade 3-4 granulocytopenia. Treatment with S9788 was cardiotoxic as it caused a dose-dependent and reversible increase in corrected QT intervals as well as clinically non-significant arrhythmias on 24- or 48-h Holter recordings. Although clinically relevant cardiac toxicities did not occur, the study was terminated as higher doses of S9788 may increase the risk of severe cardiac arrhythmias. Twenty-nine patients treated with S9788 plus doxorubicin were evaluable for response, and one patient, who progressed after treatment with doxorubicin alone, achieved a partial response. We conclude that S9788 administered at the doses and schedule used in this study results in relevant plasma concentrations in humans and can safely be administered in combination with doxorubicin.

Adult↗

PubMed1997

Increasing the use of advance directives in medical outpatients.

OBJECTIVE: We studied whether a simple educational intervention would increase patient completion of advance directives and discussions on end-of-life issues. DESIGN: Randomized, controlled trial. SETTING: Outpatient clinic of a teaching hospital. SUBJECTS: One hundred eighty-seven outpatients of a primary care internal medicine clinic. INTERVENTION: Study subjects attended a 1-hour interactive seminar and received an informational pamphlet and advance directive forms. Control subjects received by mail the pamphlet and forms only. MEASUREMENTS AND MAIN RESULTS: Completion of the advance directive was the main measurement. There were no significant differences in baseline characteristics of either group. Follow-up at 1 month revealed advance directive completion in 38% of study versus 24% of control subjects (p = .04), and discussions on advance planning in 73% of study versus 57% of control subjects (p = .02). Patients most likely to complete the documents were white, married, or attendees at the educational seminar. CONCLUSIONS: Interactive group seminars for medical outpatients increased discussions and use of written advance directives.

Adult↗