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Biomedical subjects

C Lucas

Publications and source records attributed to C Lucas.

At least 109 records · Page 6Linked to original sources
PubMed1997

Role of left ventricular hypertrophy in diastolic dysfunction in aged hypertensive patients.

OBJECTIVE: To evaluate the influence of left ventricular hypertrophy (LVH) on the diastolic dysfunction in older hypertensive patients. METHODS: In total 665 patients (58% men, 61% White, aged 55-80 years) with mild-to-moderate essential hypertension underwent Doppler echocardiography. Data included left ventricular dimensions, left ventricular mass index, body mass index, E- and A-wave mitral flow velocities, E:A ratio, deceleration time > 150 ms), impaired relaxation (E:A ratio < 1.0, prolonged deceleration time according to age), and restrictive physiology (E:A ratio > 2.1, deceleration time < 150 ms)]. Data were distributed according to age (50-59, 60-69, and 70-80 years). RESULTS: The overall prevalence of sex-adjusted LVH in this study was 65%. When we compared hypertensive patients with and without LVH, the E- and A-wave velocities, E:A ratio, and deceleration time were similar. Moreover, the prevalences of normal, impaired relaxation, and restrictive physiology patterns among patients with and without LVH did not differ significantly (20, 79.5, and 0.5 versus 24, 75.5, and 0.5%). When the mitral flow patterns were adjusted according to age, the impaired relaxation pattern increased further with age (to 73% during the fifth decade, 83% during the sixth decade, and 88% during the seventh decade). CONCLUSIONS: LVH is not an independent factor associated with abnormal flow patterns in hypertensive patients aged over 50 years with normal systolic contractility. The impaired relaxation is the predominant pattern of diastolic dysfunction in older hypertensive patients and increases further with aging.

Aged↗
PubMed1997

Characteristics of Fps1-dependent and -independent glycerol transport in Saccharomyces cerevisiae.

Eadie-Hofstee plots of glycerol uptake in wild-type Saccharomyces cerevisiae W303-1A grown on glucose showed the presence of both saturable transport and simple diffusion, whereas an fps1delta mutant displayed only simple diffusion. Transformation of the fps1delta mutant with the glpF gene, which encodes glycerol transport in Escherichia coli, restored biphasic transport kinetics. Yeast extract-peptone-dextrose-grown wild-type cells had a higher passive diffusion constant than the fps1delta mutant, and ethanol enhanced the rate of proton diffusion to a greater extent in the wild type than in the fps1delta mutant. In addition, the lipid fraction of the fps1delta mutant contained a lower percentage of phospholipids and a higher percentage of glycolipids than that of the wild type. Fps1p, therefore, may be involved in the regulation of lipid metabolism in S. cerevisiae, affecting membrane permeability in addition to fulfilling its specific role in glycerol transport. Simultaneous uptake of glycerol and protons occurred in both glycerol- and ethanol-grown wild-type and fps1delta cells and resulted in the accumulation of glycerol at an inside-to-outside ratio of 12:1 to 15:1. Carbonyl cyanide m-chlorophenylhydrazone prevented glycerol accumulation in both strains and abolished transport in the fps1delta mutant grown on ethanol. Likewise, 2,4-dinitrophenol inhibited transport in glycerol-grown wild-type cells. These results indicate the presence of an Fps1p-dependent facilitated diffusion system in glucose-grown cells and an Fps1p-independent proton symport system in derepressed cells.

Aquaporins↗
PubMed1997

Cervical artery dissections.

Cervical artery dissection (CAD) accounts for up to one fifth of ischemic strokes occurring before 45 years. Their increasing recognition is probably due to an increased clinical awareness of this condition in patients with painful ischemic events. The internal carotid artery is the most commonly affected vessel. Cerebral ischemia is the most serious consequence of a CAD. It may be due to hemodynamic factors or emboli. The enlargement of the artery may lead to a direct compression of the lower cranial nerves. CAD typically occurs in young adults with a mean age of 40 years with a male:female ratio of 1.5. After exclusion of traumatic cases, the average annual incidence rate of CAD is 2.6 per 100,000, but the reported incidence figures in the literature are likely to be an underestimation of the incidence of CAD. A spontaneous dissection is assumed when no or only minor trauma preceded the onset. However, the differentiation between spontaneous and traumatic dissections is artificial because of a continuum between both forms. The pathogenesis of dissections remains unknown in most cases. However, traumas and primary diseases of the arterial wall are the main predisposing factors. The clinical presentation of spontaneous dissections of the internal carotid artery includes cerebral ischemia, cervical or cranial pain, Horner's syndrome and cranial nerve palsy; CAD may also be silent. Brainstem ischemic deficits and occipital pain are the most common findings in vertebral artery dissections, but these features may be biased because the most benign and the most severe cases may escape detection. The favorable natural history of CAD emphasizes the need for a noninvasive approach to the detection, monitoring and follow-up. This noninvasive approach can be obtained by means of CT scan, MRI, magnetic resonance angiography and ultrasonography, although angiography remains the gold standard for the diagnosis of arterial dissections. Follow-up studies suggest a fairly good overall prognosis in adults and in children. In many centers, CAD are treated by heparin at the acute stage, although the benefit of such a potentially dangerous treatment has never been proven by a randomized trial.

Adult↗
PubMed1997

Preexisting dementia in stroke patients. Baseline frequency, associated factors, and outcome.

BACKGROUND AND PURPOSE: The link between stroke and degenerative dementia, especially Alzheimer's disease, is closer than expected by chance. Dementia after stroke may be due to the cumulative effect of vascular and degenerative changes. The prevalence of dementia just before stroke onset remains unsettled. The aim of this study was to determine the frequency of preexisting dementia in stroke patients, associated factors, and consequences on outcome. METHODS: We evaluated the cognitive functioning prior to stroke in 202 consecutive patients with ischemic or hemorrhagic stroke by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We classified in the dementia group patients with IQCODE scores of 104 or more. Six months after stroke onset, survivors underwent a battery of neuropsychological tests. RESULTS: Thirty-three patients were demented before stroke (16.3%; 95% confidence interval, 11.2 to 21.4). There was no diagnosis of dementia in 32 of these 33 patients. We determined by logistic regression analysis that female sex, family dementia, leukoaraiosis, and cerebral atrophy are independently associated with prestroke dementia. All survivors who had IQCODE scores of 104 or more at the acute stage met criteria for dementia 6 months later. CONCLUSIONS: Our study showed that one sixth of stroke patients have preexisting dementia. Therefore, some patients with so-called "poststroke dementia" probably had unrecognized preexisting dementia.

Adult↗
PubMed1997

Contribution of a liaison clinical pharmacist to an inpatient palliative care unit.

The impact on patient care of interventions made by a liaison clinical pharmacist visiting a busy inpatient palliative care unit were evaluated using a validated six-point scoring system. Interventions made in 13% of patients could improve patient care, save money or both, but rarely involved the drugs that are commonly used for symptom control in patients with terminal cancer. Advice to rationalize inappropriate drug regimens (53%) was the commonest intervention, followed by warnings about drug interactions (24%) and advice about therapeutic drug monitoring (8%). The interventions were evaluated by the pharmacist, a palliative medicine registrar and two independent doctors, confirming that the pharmacist was valid and accurate in assessing her own work. Although more than 60% of interventions could significantly improve patient care, compliance by medical and nursing staff with advice was only 55%, reflecting possible tensions between palliative and general hospital medicine. This survey emphasizes the role of liaison clinical pharmacists in palliative care, the need for much more critical appraisal of prescribing practices and the utility of ranking pharmacist interventions as a quality assurance and educational tool. In particular, providing palliative care for patients with advanced acquired immunodeficiency syndrome (AIDS) is enhanced when a pharmacist with a specialist knowledge of AIDS therapeutics is available.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Action of peripheral or intrathyroidal lymphocytes on autologous thyrocytes cultured in follicles in collagen gel.

We have studied the action of peripheral blood lymphocytes (PBLs) and intrathyroidal lymphocytes (ITLs) on the biochemical and hormonal metabolism of autologous thyrocytes cultured in follicles in a collagen gel. The production of tumour necrosis factor alpha (TNF-alpha) in culture was also measured. Thyroid tissues and lymphocytes were obtained from ten patients with Graves' disease and from five control subjects. Lymphocyte-induced cytotoxicity was evaluated in autologous thyrocytes cultured in a collagen gel by several tests; neutral red uptake, lactate dehydrogenase activity and glutathione level. Hormonal metabolism was assessed by evaluating tri-iodothyronine (T3) and total cAMP production under TSH stimulation. TNF-alpha levels were measured in supernatants after 5 days of coculture. PBLs altered biochemical metabolism, T3 synthesis and cAMP production in autologous thyroid follicles. These inhibitions were greater than those obtained with ITLs. No difference was seen between cells obtained from patients with Graves' disease and those from normal subjects. TNF-alpha levels secreted by PBLs were higher than those secreted by ITLs. The concentrations of this cytokine decreased in coculture. Significant correlations were observed between the decrease in biochemical and hormonal parameters and TNF-alpha levels. Exogenous TNF-alpha and high doses of interferon gamma inhibited follicle metabolism, especially hormone secretion. In conclusion, thyrocytes cultured in follicles provide a more sensitive model than monolayer cultures for analysis of lymphocyte-induced interactions. Lymphocytes gradually inhibit the biochemical and hormonal metabolism of autologous thyroid follicles depending on the isolation method. These alterations may be particularly attributed to TNF-alpha secreted by lymphocytes. The cytokine-induced inhibition of thyroid hormonal function apparently involves the adenylate cyclase system.

Adult↗
PubMed1997

Arterial ischemic strokes associated with pregnancy and puerperium.

Physiological changes occurring during pregnancy and puerperium may increase the risk of stroke. However, the incidence rate of ischemic stroke is of 3.8 to 5 in 100,000 pregnancies, i.e. quite similar to that of ischemic strokes occurring in non pregnant women of child bearing age. Whereas eclampsia, choriocarcinoma and amniotic emboli occur only during pregnancy or puerperium, peripartum cardiomyopathy and benign cerebral angiopathy are less specific. All other causes of cerebral ischemia may also occur during pregnancy and puerperium. The management of an ischemic stroke should not differ between pregnant and non pregnant women of child bearing age. Strokes associated with pregnancy require a complete diagnostic work-up including angiography if necessary. Low doses of aspirin (60-80 mg/d) can be used after 3 months of pregnancy. Heparin is the anticoagulant of choice during pregnancy, but warfarin may be used between 13 and 36 weeks of gestation; heparin and warfarin can be used during breast feeding. There is no neurological reason to recommend a systematic use of cesarean section. Subsequent prescription of oral contraceptive therapy is not recommended except in patients with a definite cause of ischemic stroke which is not influenced by hormones.

Arterial Occlusive Diseases↗
PubMed1997

[Effectiveness and tolerance of three month sustained release leuprorelin in the treatment of metastatic prostatic cancer (comparative, randomized, multicentric study].

OBJECTIVE: To establish the pharmacodynamic and safety equivalence between 2 sustained-release forms of leuprorelin 11.25 mg and 3.75 mg, in the treatment of metastatic prostatic carcinoma. METHODS: 44 patients received subcutaneous injections of leuprorelin for 9 months (randomization: 2/l): either 11.25 mg every three months (n = 29) or 3.75 mg monthly (n = 15). Main criterion: centralized monthly assay of plasma testosterone (T). RESULTS: The equivalence of the 2 forms in terms of mean plasma testosterone was demonstrated (p = 0.002): 1 month: T = 0.19 +/- 0.03 ng/ml; 3 months: T = 0.27 +/- 0.04 ng/ml. Exploratory analysis did not reveal any significant difference between the groups for the number of patients castrated at each visit or for the number of patients with all T values < or = 0.5 ng/ml, or for clinical responses or safety. CONCLUSION: The 2 forms have a comparable efficacy and safety.

Adenocarcinoma↗
PubMed1997

[Tolerance and clinical and biological responses during the first 6 months of treatment with 1-month sustained release LHRH agonists leuprolerin and triptolerin in patients with metastatic prostate cancer].

OBJECTIVES: Comparative efficacy and safety of 2 LHRH analogues in metastatic prostatic carcinoma. METHODS: 68 patients received monthly injections for 6 months (randomization): either subcutaneous leuprolide 3.75 mg LP (n = 36), or intramuscular triptorelin 3.75 mg LP (n = 32). (Flare-up prevention: nilutamide). Parameters re-evaluated at 1.3 and 6 months: centralized assays of plasma testosterone (T), LH and serum PSA; clinical symptoms. Main criterion: proportion of patients with T < or = 0.5 ng/mL. RESULTS: The percentages of patients with T < or = 0.50 ng/mL was not significantly different between the two groups and were equal to 100 and 90%, 97 and 100%, and 100 and 96% at the 3 study times, for leuprolide or triptorelin, respectively. The difference was significant at 1 month on complementary analysis at the limit of T < 0.30 ng/mL: 86% with leuprolide versus 60% with triptorelin (p = 0.02) and for mean plasma testosterone: 0.16 +/- 0.10 ng/mL versus 0.33 +/- 0.44 ng/mL, respectively (p = 0.02). The clinical subjective efficacy was not significantly different. CONCLUSION: Both treatments were effective, although plasma testosterone fell more rapidly with leuprolide. No conclusion about the possible clinical or survival benefits can be formulated. Overall safety was satisfactory.

Adenocarcinoma↗
PubMed1996

Isolation and characterisation of mutants from the halotolerant yeast Pichia sorbitophila defective in H+/glycerol symport activity.

Pichia sorbitophila, a yeast species that is highly resistant to osmotic stress in general and to salt stress in particular, was subjected to a mutagenesis strategy in order to obtain mutants deficient in the glycerol active uptake previously described. Density centrifugation was used for enrichment of NaCl sensitive mutants in either glucose or glycerol media. Several phenotypic classes of mutants were identified, to which physiological tests were applied concerning the activity of the symporter, its accumulation capacity and the detection of the activity of glycerol pathway specific enzymes. From these, two mutant strains were selected, presenting a clearly deficient phenotype on H+/glycerol symport activity.

Biological Transport, Active↗
PubMed1996

[Benign angiopathy of the puerperium: a clinicoradiological case associated with ingestion of bromocriptine].

We report a case of benign cerebral angiopathy in a 37 year-old woman in the postpartum period occurring after bromocriptine therapy to suppress lactation. She presented with severe headache, hyperthermia and bradycardia. She had partial seizure. Angiography excluded cortical vein thrombosis but revealed multiple narrowing of intracerebral arteries. Bromocriptine was stopped. The patient totally recovered. A second angiography performed 3 months later was normal. Postpartum cerebral angiopathy is considered as rare but the prevalence is probably underestimated. Neurological features of this affection are multiple. Diagnosis is made by angiography performed in emergency and which showed narrowing of intracerebral arteries which are reversible. Prognosis is good. Reversible vasoconstriction may be due to acute arterial hypertension, sometimes triggered by ergot derivatives.

Adult↗
PubMed1996

Pharmacokinetics and pharmacodynamics of nitrosourea fotemustine: a French cancer centre multicentric study.

The nitrosourea, fotemustine, was given intravenously in 1 h constant-rate infusion to 66 patients in a multicentric study to assess both fotemustine pharmacokinetic behaviour and the pharmacokinetic-pharmacodynamic relationships. Depending on the tumour type treated, two administration and sampling protocols were used: 100 mg/m2/week as a conventional dose (six samples, 44 patients) and 300-500 mg/m2/day as a high dose (10 samples, 22 patients). The 91 time-concentration curves were best described by either a one-(55) or a two-compartment (36) model, and their mean clearance values did not differ significantly (85.3 +/- 6.5 and 101.3 +/- 9.5 l/h, respectively, P = 0.1727). Fotemustine pharmacokinetics were not influenced by repeated treatment (time-independence) nor by dose level (dose-independence). The pharmacodynamic effect observed on white blood cell count was expressed by a logit regression model involving the area under the curve mainly and the total administered dose. White blood cell toxicity could be predicted as a function of the dose for a given patient with a known fotemustine clearance value.

Adult↗
PubMed1996

Inhibition of posterior capsule opacification by an intraocular-lens-bound sustained drug delivery system: an experimental animal study and literature review.

PURPOSE: To find a way to prevent or significantly reduce posterior capsule opacification (PCO) with modern phacoemulsification and in-the-bag intraocular lens (IOL) implantation. SETTING: Department of Ophthalmology and Institute for Pharmaceutical Technology and Biopharmacy, Ruprecht-Karls-University of Heidelberg, Germany. METHODS: We evaluated the effects of an IOL-bound sustained drug delivery system (SDDS) consisting of the carrier substance poly-DL-lactid and the drug daunorubicin or indomethacin. The system was applied to the IOL surface and implanted in rabbit eyes. At 8 weeks postoperatively, PCO wet mass was determined. Toxic and inflammatory effects were documented by histopathology. RESULTS: The average PCO wet mass was 54.6 mg in the control group, 28.6 mg with daunorubicin, and 64.1 mg with indomethacin. Statistical analysis showed a significant reduction of PCO with daunorubicin (Mann-Whitney U-test, P = .025) and no PCO-reducing effect with indomethacin. Light microscopy of the specimens revealed mild inflammation, especially at the limbus, and some endothelial cell loss in the daunorubicin group and iris and ciliary body inflammation in the indomethacin group. CONCLUSION: In the rabbit eye, slow release of daunorubicin reduced PCO formation by approximately 50%. It must be determined whether the endothelial side effects are specific to the rabbit species or whether the human cornea is as sensitive. The principle of the IOL-bound SDDS and the evaluation procedure can be standardized and used for systematic tests in the future.

Animals↗
PubMed1996

Effect of S9788 on the efficiency of doxorubicin in vivo and in vitro in medullary thyroid carcinoma xenograft.

In medullary carcinoma of the thyroid (MTC), drug resistance remains the major obstacle to effective chemotherapy. In this work, we studied the effect of S9788 on doxorubicin (DOX) efficiency in a MTC cell line (TT cells) injected in nude mice. After two passages, TT cells were injected in 40 nude mice divided into four groups [controls and groups receiving DOX alone (10 mg/kg), S9788 alone (50 mg/kg) or both DOX + S9788]. The weight of the mice, tumoral volume (TV), doubling time (DT) of the tumor and survival time of mice were evaluated in each group. In addition, the efficiency of DOX with or without S9788 was assessed by the inhibition of tumoral growth and specific growth delay. In vitro, glycoprotein P 170 (P-gp) was detected on tissular sections and on tumoral cells by immunocytochemistry or flow cytometry with several monoclonal antibodies: JSB1, MRK 16, C219 and UIC2. In vivo the weight of the mice decreased slightly with DOX and dropped dramatically with DOX + S9788. The DT of the tumors increased with DOX over controls (22.5 +/- 8.5/12.7 +/- 3.9 days) and showed a higher value with DOX + S9788 (29.2 +/- 11.4 days). Inhibition of tumoral growth, 89% with DOX, fell to 47.6% with DOX + S9788. Specific growth delay increased with the double treatment (130 versus 75% with DOX alone). In vitro, P-gp was not detected on tissular sections and cells whatever the method and the antibody used. In conclusion, S9788 potentiates the efficiency of DOX treatment in vivo. The absence of P-gp may result from the absence of translation of the MDR1 gene. The reversal effect of S9788 may involve another resistance mechanism such as the MDR Sister of MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Risk factors and leukoaraiosis in stroke patients.

OBJECTIVES: Although leukoaraosis (LA) is a common CT findings, its pathogenesis remains debated: if small-artery pathology may explain in some cases white matter changes, many other factors, such as hemodynamic perturbations, might also lead to LA. To test these hypothesis, we determined the types of cerebrovascular risk factors associated with leukoaraosis in consecutive patients with acute cerebrovascular event. PATIENTS AND METHODS: Using CT-scans, we prospectively studied in 610 patients consecutively admitted for an acute cerebral event, the relation between LA and the following cerebrovascular risk factors: age, sex, arterial hypertension, diabetes mellitus, hyperlipemia, alcohol consumption, birth contraceptive pills, previous transient ischemic attack or stroke, migraine, atrial fibrillation, valvulopathy, coronaropathy, left ventricular hypertrophy, stenosis of the internal carotid artery, by means of a multiple linear regression. Relation with cerebral atrophy was also evaluated. RESULTS: We found LA scores to depend on increasing age (p = 0.0001), female sex (p = 0.0146), history of stroke or TIA (p = 0.0051), history or current atrial fibrillation (p = 0.0083), increasing cerebral atrophy score (p = 0.0001), absence of hyperlipemia (p = 0.0003) and absence of alcohol consumption higher than 300 g/week (p = 0.0398). CONCLUSION: Our findings do not support the hypothesis that, in stroke patients, LA share similar risk factors than small-vessel disease; other cerebrovascular risk factors may also contribute to LA, perhaps because of decreased cerebral blood flow.

Adolescent↗
PubMed1996

Helical CT for the diagnosis of extracranial internal carotid artery dissection.

BACKGROUND AND PURPOSE: We attempted to evaluate the sensitivity of helical CT for the diagnosis of extracranial internal carotid artery (ICA) dissection. METHODS: Sixteen consecutive patients with 18 angiographically confirmed extracranial ICA dissections were studied with a helical CT protocol with large-volume acquisition and thin axial slice reconstructions. A control group including normal and atherosclerotic ICAs was formed for comparison, and a blind interpretation of CT images was made by two observers. We evaluated the presence of stenosis, eccentric lumen, mural thickening, aneurysm, occlusion, and annular contrast enhancement. When the artery seemed to be occluded, we measured the external diameter of the ICA (1) on the occluded side, at its upper portion and most enlarged level, (2) at its lower portion, beyond the bulb, and (3) on the contralateral side, at is upper portion. RESULTS: Interobserver agreement was good except for the presence of annular contrast enhancement. In the stenotic dissection group (n=12), the presence of a narrowed eccentric lumen at the upper portion of the ICA on axial CT images was classified correctly in all cases (sensitivity, 100%; specificity, 100%). An arterial wall thickening was seen in all cases of dissection but also in three cases of the control group. In the occlusive dissection group (n=6), the enlargement of the dissected artery was the best criterion (sensitivity, 100%, specificity, 100%) for occlusive dissection. CONCLUSIONS: Helical CT seems to be a reliable method for evaluating extracranial ICA dissection. The analysis of the residual arterial lumen and the measurement of the external diameter of the carotid artery were the best criteria for the diagnosis. Further studies with larger groups are required to determine whether ICA dissections might be diagnosed using helical CT as a first procedure.

Adult↗