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Biomedical subjects

C Lucas

Publications and source records attributed to C Lucas.

At least 37 records · Page 2Linked to original sources

Benefits of treating highly disabled migraine patients with zolmitriptan while pain is mild.

Clinical trials of migraine therapy often require treatment when migraine pain intensity is moderate or severe, but many physicians find this practice artificial and patients often prefer to treat while pain is mild. This randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg in treating migraine while pain is mild, in patients who typically experience migraine attacks that are initially mild, but progress to moderate or severe. The intent-to-treat population comprised 280 patients (138 zolmitriptan; 148 placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo). Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 h (43.4% vs. 18.4% placebo; P < 0.0001). Significantly fewer zolmitriptan patients reported progression of headache pain to moderate or severe intensity 2 h postdose (53.7% vs. 70.4% placebo; P < 0.01), or required further medication within 24 h (46.4% vs. 71.1% placebo; P < 0.0001). The efficacy of zolmitriptan was more pronounced in patients treating during the first 15 min following pain onset. Adverse events were reported in 31.2% of patients treated with zolmitriptan (vs. 11.3% for placebo), and the incidence was lower in patients who treated early after attack onset. Zolmitriptan provides high efficacy when treating migraine while pain is mild, with the clinical benefits being more pronounced when treating early after migraine onset.

Activities of Daily Living↗

The role of multisensor data fusion in neuromuscular control of a sagittal arm with a pair of muscles using actor-critic reinforcement learning method.

In this study, we consider the role of multisensor data fusion in neuromuscular control using an actor-critic reinforcement learning method. The model we use is a single link system actuated by a pair of muscles that are excited with alpha and gamma signals. Various physiological sensor information such as proprioception, spindle sensors, and Golgi tendon organs have been integrated to achieve an oscillatory movement with variable amplitude and frequency, while achieving a stable movement with minimum metabolic cost and coactivation. The system is highly nonlinear in all its physical and physiological attributes. Transmission delays are included in the afferent and efferent neural paths to account for a more accurate representation of the reflex loops. This paper proposes a reinforcement learning method with an Actor-Critic architecture instead of middle and low level of central nervous system (CNS). The Actor in this structure is a two layer feedforward neural network and the Critic is a model of the cerebellum. The Critic is trained by the State-Action-Reward-State-Action (SARSA) method. The Critic will train the Actor by supervisory learning based on previous experiences. The reinforcement signal in SARSA is evaluated based on available alternatives concerning the concept of multisensor data fusion. The effectiveness and the biological plausibility of the present model are demonstrated by several simulations. The system showed excellent tracking capability when we integrated the available sensor information. Addition of a penalty for activation of muscles resulted in much lower muscle coactivation while keeping the movement stable.

Algorithms↗

Impairment of endothelial function in patients with spontaneous cervical artery dissection: evidence for a general arterial wall disease.

BACKGROUND AND PURPOSE: Cervical artery dissection (CAD) accounts for 10-20% of ischemic strokes in young adults. Although trauma and preexisting disorders of the arterial wall are the main predisposing factors, most CADs are considered 'spontaneous'. We hypothesized that CAD could originate in systemic vascular disease bound to the intima-media interface without clinical signs. If this hypothesis is true, endothelium-dependent vasodilation would be impaired in response to a physiological stimulus such as an increase in blood flow. METHODS: Flow-mediated arterial dilation was studied in 65 consecutive patients with spontaneous CAD: 26 with carotid artery dissection (ICAD), and 39 with vertebral artery dissection (VAD). CAD patients with vascular risk factors, trivial or obvious cervical trauma, or connective tissue disease were excluded. Twenty-three patients with ischemic stroke of unknown cause were included as controls. Using high-resolution ultrasonography, brachial artery diameter was measured at rest, during post-ischemic hyperemia (flow-mediated endothelium-dependent dilation), and after sublingual glyceryl trinitrate spray (endothelium-independent dilation). RESULTS: The mean +/- SD values of the flow-mediated vasodilation index were 5.7 +/- 6.2% in ICAD, 5.0 +/- 9.3% in VAD and 13.2 +/- 6.5% in controls (p < 0.0005), without any difference between ICAD and VAD. Endothelium-independent dilation mean values were 21.5 +/- 9.5% in ICAD, 25.1 +/- 12.5% in VAD, and 20.8 +/- 8.4% in controls, without a significant difference between groups (p = 0.49). CONCLUSIONS: These results give evidence of impaired endothelium-dependent vasodilation in CAD patients that is not the result of stroke, and suggest that an underlying abnormality of the arterial wall layers may predispose to CAD.

Adult↗

Angioplasty and stenting for high-grade internal carotid artery stenosis: safety study in 39 selected patients.

BACKGROUND: Carotid angioplasty and stenting (CAS) is sometimes used as an alternative to surgery, despite the lack of evidence for its safety and efficacy. METHOD: Over a 33-month period, 39 consecutive patients with a stenosis >/=70% underwent CAS (4 in a randomized trial and 35 because of contra-indications for surgery). RESULTS: In 5 patients (13%; 95% CI: 3-23), a major complication occurred (3 disabling ischaemic strokes, 1 myocardial infarction, 1 acute interstitial nephropathy). In 7 patients (18%; 95% CI: 6-30), a minor complication occurred (5 transient ischaemic attacks, 1 transient confusional state, 1 non-disabling ischaemic stroke). CONCLUSION: CAS cannot be considered as a routine procedure and should be restricted to high-risk patients unfit for surgery.

Adult↗

Percutaneous transluminal angioplasty of proximal vertebral artery stenosis: long-term clinical follow-up of 16 consecutive patients.

We report long-term (average 30 months) clinical and radiological follow-up of 16 consecutive patients with uni- or bilateral proximal vertebral artery stenosis who underwent percutaneous transluminal angioplasty (PTA), without stenting, between 1995 and 1998. Assessment was performed by an independent neurologist. All patients but one remained asymptomatic during follow-up; moderate restenosis was observed in four. PTA of the proximal vertebral artery is safe but in the absence of knowledge of the natural history of atherosclerotic vertebral artery stenosis, whether it is beneficial or not remains unproven. The decision as to whether to perform this procedure is individual.

Adult↗

Cerebral venous thrombosis 3-year clinical outcome in 55 consecutive patients.

An early diagnosis and heparin therapy have contributed to a decreased mortality in cerebral venous thrombosis (CVT). However, predictors of outcome are difficult to identify, because most studies suffered heterogeneity in diagnostic findings and treatments, retrospective design, and recruitment bias. The aim of this study was to evaluate the clinical outcome in 55 consecutive patients with CVT admitted over a 4-year period. The study population consisted of 42 women and 13 men, with a median age of 39 years (range 16-68). The diagnosis was performed with MRI in 53 patients, and angiography in 2. The outcome was assessed with the modified Rankin scale (mRs). After a median follow-up of 36 months (range: 12-60), 45 patients were independent (mRS 0-2), and 10 were dependent or dead (mRS 3-6). Of 48 survivors, 7 had seizures, 6 motor deficits, 5 visual field defects, 29 headache (migraine in 14, tension headache in 13, other in 2). The logistic regression analysis found focal deficits and cancer at time of diagnosis, as independent predictors of dependence or death at year 3, and isolated intra-cranial hypertension as an independent predictor of survival and independence. Mortality rates are low in the absence of cancer and focal deficits, and more than 80 % of survivors are independent after 3 years. However, 3/4 of survivors have residual symptoms. Therefore, despite a low mortality rate, CVT remains a serious disorder.

Adult↗

Efficacy of low-level laser therapy in the management of stage III decubitus ulcers: a prospective, observer-blinded multicentre randomised clinical trial.

Low-level laser therapy (LLLT) has been suggested as a promising treatment option for open wounds. In view of the absence of randomised studies with sufficiently large sample sizes, we assessed the efficacy of LLLT in the treatment of stage III decubitus ulcers. We performed a prospective, observer-blinded multicentre randomised clinical trial to assess the effect of LLLT as adjuvant to standard decubitus care. A total of 86 patients were enrolled into the study. Treatment was the prevailing consensus decubitus treatment (n=47); one group (n=39) had LLLT in addition, five times a week over a period of 6 weeks. The primary outcome measure was the absolute (mm2) and relative (%) wound size reduction at 6 weeks compared to baseline. Secondary outcome measures were the number of patients developing a stage IV ulcer during the study period, and the median change in Norton scores at 6 weeks compared to baseline. Based on the intention-to-treat principle, using last-observation-carried-forward analyses, Mann-Whitney U tests showed that the differences between the two groups in terms of absolute improvement (p=0.23) and relative improvement (p=0.42) were not significant. Because the wound size areas were non-normally distributed, we also analysed the data after logarithmic transformation of the wound size measurements. No significant difference in log(e) improvement scores between groups could be demonstrated (unpaired t-test: p=0.59). During the treatment period 11% of the patients in the control group and 8% of the patients in the LLLT group developed a stage IV decubitus ulcer (Fisher's exact test: p=0.72). The patients' Norton scores did not change during the treatment period. In this trial we found no evidence that justifies using low-level laser therapy as an adjuvant to the consensus decubitus ulcer treatment.

Aged↗

Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients.

BACKGROUND: Patients with relapsing or refractory multiple myeloma have poor prognosis. Few compounds are active in these patients and response duration remains short. We report the results of an open phase II trial evaluating the efficacy and safety of fotemustine monotherapy. PATIENTS AND METHODS: Twenty-one patients with relapsing (17) or refractory (four) multiple myeloma received fotemustine 100 mg/m(2) on an outpatient basis on days 1 and 8 of the induction cycle, followed after a 6-week rest period by fotemustine 100 mg/m(2) every 3 weeks until progression or unacceptable toxicity. Fotemustine pharmacokinetics during the first day of induction was compared between patients with normal or abnormal renal function. RESULTS: Five of 20 eligible patients had an objective response giving an intention-to-treat response rate of 25% [95% confidence interval (CI) 6% to 44%] and a 35.7% response rate (95% CI 11% to 61%) in the 14 patients having received at least four injections of fotemustine. The median time to objective response was 8.9 months. The median times to progression and survival were 13.8 and 23.1 months, respectively, with a 2-year survival rate of 49%. The main toxicity was myelosuppression with grade 3-4 neutropenia and thrombocytopenia in 66% and 71% of patients, respectively. There was one toxic death by sepsis after induction. The pharmacokinetic parameters in renal-impaired patients were not significantly different from those in patients with normal renal function with a similar incidence of grade 3-4 toxicity in both groups. CONCLUSIONS: Fotemustine as a single agent has definite activity in patients with relapsing or refractory multiple myeloma, with acceptable toxicity and can be administered at conventional doses in patients with mild or moderate renal impairment.

Aged↗

[Peripheral haemosiderosis of the central nervous system].

We report 2 cases of patients with hemosiderosis of the central nervous system. The diagnosis was made in 1999 in a stroke unit. The patients had both deafness, but their clinical presentation was different, due to heterogeneous features of this pathology. Hemosiderosis of the central nervous system is due to chronic subarachnoidal hemorrhage. Magnetic resonance imaging is extremely sensitive to the presence of hemosiderin and is the investigation of choice enabling diagnosis and sometimes bleeding source (50 p. cent). The interest of our observations concerned the source of bleeding. In the first patient, diagnostic work-up was negative. For the second one, the deposition of hemosiderin was explained by 3 possible sources. If a bleeding source can be identified, surgery is the optimal treatment. Copper chelation, like Trientine can be used, but there is no evidence-based for using this treatment.

Adolescent↗

Prevalence and clinical characteristics of migraine in France.

OBJECTIVE: To determine the prevalence and clinical features of migraine and related headache types in France. METHODS: The authors recruited a population of subjects with headache representative of the national population using a stratified sampling method. They screened 10,585 subjects aged 15 and older who were representative of the general population. They identified 1,486 of these as having headaches, and these subjects were subsequently interviewed for information on clinical features, natural history, and functional impact of headache. The authors categorized subjects based on the International Headache Society (IHS) classification and assessed disability using the MIDAS questionnaire. RESULTS: The authors found a standardized prevalence for migraine (IHS categories 1.1 and 1.2) of 7.9% (11.2% for women and 4.0% for men) and 9.1% for migrainous disorder (IHS category 1.7). Migraine attacks were associated with a considerable degree of handicap in activities of daily living, with a MIDAS grade distribution of 74.7% (grade 1), 13.3% (grade 2), 7.7% (grade 3), and 4.3% (grade 4). The prevalence of migraine with MIDAS grade 3 or 4 was 1.6%. CONCLUSIONS: The prevalence of migraine (IHS categories 1.1 and 1.2) in France is 7.9%, and that of total migraine is 17.0%; this does not seem to have evolved over the past 10 years.

Adult↗

Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke.

OBJECTIVE: To determine the 3-year outcome in 287 young adults (15 to 45 years old) consecutively admitted between 1992 and 1996 for an ischemic stroke. METHODS: Follow-up was obtained with clinical examinations or telephone interviews, and data were recorded about risk factors, associated disorders, causes of stroke, and current treatments. Functional outcomes were classified with the modified Rankin Scale (mRS). Endpoints were stroke recurrence, myocardial infarction, epileptic seizures, and death. RESULTS: After a mean follow-up of 3 years, no patient was lost to follow-up; 25.4% of the follow-up visits were performed by telephone interview. The authors found 1) an annual mortality rate of 4.5% during the first year and then of 1.6%; 2) an annual stroke recurrence rate of 1.4% during the first year and then of 1.0%; 3) a 0.2% annual rate of myocardial infarct; 4) epileptic seizures occurring in 6.6% of patients, during the first year in most patients; 5) independence (mRS = 0 to 2) in 94.0% of patients; 6) 4.2% of patients lost their job after stroke despite an mRS score of < or =1; 7) 7.0% of patients reported divorce; and 8) only 22.2% of smokers gave up smoking. CONCLUSION: Although young patients who experience ischemic strokes have a low risk of stroke recurrence and myocardial infarction, some patients do not regain independence.

Adolescent↗

Wound healing in cell studies and animal model experiments by Low Level Laser Therapy; were clinical studies justified? a systematic review.

Based on results of cell studies and animal experiments, clinical trials with Low Level Laser Therapy (LLLT) were performed, which finally did not demonstrate a beneficial effect on outcome of wound healing. The aim of this study was to investigate whether the evidence from cell studies and animal experiments with respect to wound healing was unequivocally in favour of LLLT, which would imply that these models might be adequate to predict treatment response in patients, or that the data of cell studies and animal experiments were inconclusive, which would mean that the clinical trials were based on insufficient evidence. We performed a systematic review of cell studies and animal experiment with LLLT on wound healing. Manuscripts were identified by searching Medline, Embase, and SPIE (the International Society for Optical Engineering). We assessed whether studies showed a beneficial effect of active treatment or not. The effect size was expressed in standardised mean difference [(SMD) the mean outcome measure of the treatment group minus the mean outcome measure of the control group, divided by the pooled standard deviation of these measurements]. In-depth analyses were performed on (1) studies in which inflicted wounds on animals were irradiated and evaluated; (2) studies with primary outcome measures on dimensions with direct reference to wound healing (ranging from acceleration of wound closure to epithelialisation, but excluding surrogate dimensions with regard to wound healing; in this case: tensile strength); (3) animal studies with 'true controls'; (4) studies in which animals functioned as their 'own controls' and (5) studies with the highest methodological quality score. The 36 included studies contained 49 outcome parameters of which 30 reported a positive effect of laser irradiation and 19 did not. Eleven studies presented exact data about the effect of active treatment and controls. The pooled effect size (SMD) over 22 outcome measures of these studies was - 1.05 (95% Cl: - 1.67 to - 0.43) in favour of LLLT. Methodological quality of the studies was poor. In-depth analysis of studies showed no significant pooled effect size in studies with highest methodological quality scores [0.06 (95% CI:- 0.42 to 0.53)]. Summarising the data of cell studies and animal experiments, reviewed in this manuscript, these studies failed to show unequivocal evidence to substantiate the decision for trials with LLLT in a large number of patients. In fact, there were no differences between the results of these experiments and clinical studies. Remarkably, we found that (almost from the introduction on) animal experiments and clinical studies that address the biological effects of LLLT on wound healing, ran simultaneously, rather than in sequence. We conclude that this type of phototherapy should not be considered a valuable (adjuvant) treatment for this selected, generally therapy-refractory condition in humans.

Animals↗

Clinical phase I and pharmacokinetic study of S 16020, a new olivacine derivative: report on three infusion schedules.

S 16020, a new 9-OH olivacine derivative, is a novel topoisomerase II inhibitor with activity in cell lines presenting the classical multidrug resistance phenotype. This report summarizes, in addition to pharmacokinetic data, the whole phase I clinical experience of S 16020 using three different infusion schedules. Asthenia and skin toxicity were the main side effects. In an attempt to understand the skin toxicity mechanism, experiments in animals were performed, the results of which are reported. S 16020 showed rapid tumor necrotizing activity in some patients, with soft tissue metastases of epidermoïd tumors and pain at the tumor site. To document the side effects of S 16020 and tumor site reactions (pain, edema, inflammatory signs), inflammatory parameters and some cytokines were measured. In our patients there was no hemolysis and no detection of anti-S 16020 antibodies, confirming the absence of immunogenicity of the compound. Based on the overall data of the three infusion schedules of S 16020, the dose of 100 mg/m(2) over 3 h every 3 weeks was selected for phase II studies.

Adult↗

Prediction of lupus nephritis in patients with systemic lupus erythematosus using artificial neural networks.

Artificial neural networks are intelligent systems that have been successfully used for prediction in different medical fields. In this study, efficiency of neural networks for prediction of lupus nephritis in patients with systemic lupus erythematosus (SLE) was compared with a logistic regression model and clinicians' diagnosis. Overall accuracy, sensitivity and specificity of the optimal neural network were 68.69, 73.77 and 62.96%, respectively. Overall accuracy of neural network was greater than the other two methods (P-value < 0.05). The neural network was more specific in predicting lupus nephritis (P-value < 0.01), but there was no significant difference between sensitivities of the three methods. Sensitivities of all three methods were greater than their specificities. We concluded that neural networks are efficient in predicting lupus nephritis in SLE patients.

Algorithms↗

[Giant arteriovenous malformation of the vein of Galen in a 50 year old man].

True malformations of the vein of Galen are usually diagnosed within the first weeks of life. They represent less than 1 p. 100 of the cerebral arteriovenous malformations. These true malformations are exceptional in adults but should be known as an endovascular treatment could be performed. The most frequent clinical presentation is a severe cardiac failure leading to death. We report a giant arteriovenous malformation of the vein of Galen in a right-handed, 50 year-old man. During childhood, he suffered from a compensated cardiac failure which remained of unknown cause. Neurological examination showed kinetic and static cerebellar syndrome and a Parinaud syndrome. A cerebral MRI scan revealed a giant vascular malformation of the vein of Galen with a normal posterior fossa. The angiography enabled the diagnosis of a true malformation of the vein of Galen in its choroidian form. Its high blood flow entails cardiac failure because of a steal phenomenon. An endovascular treatment was declined because of numerous arterial afferences and the potential risks of peroperative haemorrhage.

Cardiac Output, Low↗

Lessons from the year 2001 Mycosphaerella graminicola epidemic on winter wheat in Belgium.

Infection by Mycosphaerella graminicola (anamorph Septoria tritici) was monitored between April and July 2001 on F6 to flag leaf in 11 farmers' fields or fungicide trials. Data were analysed by mean of the decision support system "Proculture" which links an automatic weather station of the PAMESEB network to a particular field, simulates plant development with adjustment by one phenological observation during the stem elongation and analyses superposition of emerged leaves and infection events (http://www.fymy.ucl.ac.be/proculture). Several climatic events favourable for the infection and dissemination of M. graminicola occurred between October 2000 and March 2001 and allowed build up of a large amount of inoculum on the lower leaves at the end of the winter. The start of stem elongation was associated with frequent rainy periods during April, causing early infection of F5, F4 and up to F3 in some precocious fields. Dry weather with only a few local showers during most of May and June slowed down spread of infection to the upper leaves, leading to absence of M. graminicola infection of the flag leaf in 9 out of the 11 fields. Yield increase by a single fungicide spray ranged from 800 to 2200 kg/ha. A second treatment was cost effective in none of the fields. The interest and limitation of the decision support system for understanding M. graminicola epidemic and for guiding decision on spray timing are discussed.

Belgium↗

Nitrogen exchanges: testing the hypothesis of a country without agricultural production.

Today, finding data on agricultural nitrogen balances is quite easy. Calculations of such balances are carried out by most of the European countries as an indicator of environmental pollution attributable to the agricultural sector. In France, average values of agricultural nitrogen balances show an excess of 1.5 to 2 million tons of nitrogen. This excess is enormous. What would the balance of a country be if agricultural activity were stopped? In the following article, a country (France is used as an example) without agriculture is studied in order to assess its nitrogen balance. Using a previously published model describing nitrogen input and output of a given country, nitrogen flows are identified. Inputs include deposition, fixation, and products not intended for agricultural use. Outputs are reduced to zero if agriculture disappears (in France, agriculture is the only sector exporting products containing nitrogen). All flows are calculated considering the hypothesis of disappearance of agriculture. Nitrogen requirements to feed people and pets in France are estimated based on medical and veterinary data (recommended daily amounts for proteins and/or usual average consumption). Indeed, most of the food that nourishes the French population is produced nationally. If agriculture stops, it will be necessary to import food from foreign countries. Results show an unexpectedly high excess (for a country without agriculture having a structure similar to France: number of human beings and pets) of 1.5 million tons of nitrogen. An attempt to calculate an agricultural balance with the same data gives a result close to 3 million tons. Differences in French agricultural balances found in the literature can mainly be explained by values taken into account for deposition and fixation (values used here are at least 300,000 tons higher than values used by the Organisation for Economic Co-operation and Development). In conclusion, nitrogen excess in agriculture is partly due to social demand; agriculture does not only produce food but also includes many other functions (landscape management, employment, and preservation of culture, for example). As a consequence, efforts that do not involve suppressing agriculture should be made to figure out alternative ways of production.

Agriculture↗