Search PubMed⌕ Search

Biomedical subjects

T Moreau

Publications and source records attributed to T Moreau.

At least 55 records · Page 3Linked to original sources

Short and long-term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomized trial.

A potential advantage of primary over adjuvant chemotherapy in breast cancer survival had been proposed on theoretical grounds. In 1994, early results of the S6-trial comparing primary chemotherapy vs. adjuvant chemotherapy for operable breast cancer in 390 premenopausal patients had shown significant improvement in survival of the primary chemotherapy arm (p = 0.04). An updated analysis conducted in 1995 showed the disappearance of this difference between the two arms (p = 0.18). In the present analysis, we investigated the potential short and long-term benefits attributable to primary chemotherapy by applying weighted logrank tests designed to assess specifically these effects. Results were compared to those obtained with the classical logrank test. At a median follow-up of 105 months, a significant short-term survival benefit (p = 0.02) in favor of the primary chemotherapy has been shown. However, no long-term survival benefit (p = 0.36) could be documented. The classical logrank test had revealed no significant difference (p = 0.24) between the two groups but the proportional hazard assumption being rejected (p = 0.04), the efficiency of this test can be questioned. Results using the present analysis suggested that primary chemotherapy delayed early death rates, without significantly modifying long-term event rates. It emphasizes that a short-term effect which is not necessarily associated with a long-term benefit may be seen at an early evaluation and disappear later on.

Antineoplastic Agents↗

Migraine history and migraine-induced stroke in the Dijon stroke registry.

Two thousand three hundred and eighty-nine patients with first-ever stroke were registered in the population-based Dijon Stroke Registry over an 11-year period. There was a history of migraine in 49 cases (2%), with a majority of women (2.8% versus 1.1% men) with the following distribution: 27 cases among 1,380 large-artery cerebral infarctions (1.9%), 6 cases among 358 small-artery cerebral infarctions (1.6%), 6 cases among 412 cerebral infarctions due to cardiac embolism (1.4%), 7 cases among 191 cerebral hemorrhages (3. 6%) and 3 cases among 47 subarachnoid hemorrhages (6.3%). The male/female ratio was 0.58 for the 49 strokes with a history of migraine versus 1.27 for the 2,340 strokes with no history of migraine. Twelve migraine-induced ischemic strokes occurred with an infarction of the posterior area of the brain in young patients. The annual incidence was 0.80/100,000/year (confidence interval, CI = 0. 37-1.57) with a predominance of women (1.02/100,000/year, CI = 0. 52-1.25; men: 0.57/100,000/year; CI = 0.28-1.04). We conclude that a history of migraine is more frequent in women, in particular in those with hemorrhagic strokes, and that the incidence of migraine-induced stroke in our population-based study is higher in women, although it remains low.

Adolescent↗

Incidence trends of ischemic stroke and transient ischemic attacks in a well-defined French population from 1985 through 1994.

BACKGROUND AND PURPOSE: The changing incidence of ischemic stroke is of major concern in view of its public health impact, to define the population concerned, to identify risk factors, and to set up health-care systems. The aim of this study was to evaluate the time trends associated with the incidence of all the subtypes of ischemic stroke and transient ischemic attacks in a well-defined population for 10 years. METHODS: Since 1985, a population registry has recorded each patient living in Dijon (France) who suffered from a cerebrovascular disease (CVD) regardless of the type of management. This study involved all patients suffering from their first ischemic stroke and their first transient ischemic attacks (TIAs) during 1 calendar year between January 1, 1985 and December 31, 1994. The incidence changes according to age, sex, and type of cerebral ischemic event (cortico-subcortical infarct, lacunar infarct, and TIA) were studied on the basis of their annual variations. RESULTS: During the 10-year study period, 834 cortico-subcortical infarcts (52.1%), 296 lacunar infarcts (18.5%), 369 TIAs (23.1%), and 101 undetermined ischemic strokes (6.3%) were collected. The incidence of all ischemic events was relatively stable in both sexes over the 10-year period. However, the incidence rates differed according to age and type of ischemia. An increased incidence of cerebral cortico-subcortical infarct was observed in patients older than 75 years of age (+5.45% annual change [AC] in men, P<0.05; +5. 09% AC in women, NS). In parallel, a higher proportion of emboligenic cardiac arrhythmias was observed in these patients (P<0. 001). The incidence of lacunar infarcts tended to decrease, regardless of age but mainly in men under younger than 75 years of age (-12.74% AC in men, NS; +0.31% AC in women, NS). The incidence of TIAs was relatively stable in both sexes. Because our population consisted of a large number of elderly subjects, the increase in cardioembolic causes could partially explain the increased incidence of cerebral cortico-subcortical infarcts in patients older than 75 years of age. CONCLUSIONS: These preliminary data emphasize the importance of stroke surveillance in considering the variations of the different mechanisms of ischemic cerebrovascular disease. Although the incidence of TIA is stable and the incidence of lacunes tends to decrease in men, mainly before 75 years of age, we emphasize the rise of the crude incidence of cortico-subcortical infarcts in men older than 75 years of age, induced by an increase in cardioembolic causes.

Age Factors↗

[Multiple sclerosis and pregnancy: clinical issues].

Multiple sclerosis (MS) is the most common chronic disabling neurological disease affecting young women. Paradoxically, our knowledge of the relationship between pregnancy and MS is limited. However, several conclusions emerge from the literature: 1) The rate of relapse in MS decreases during pregnancy, and it rises significantly during the first three months post partum before coming back to its level prior to pregnancy. 2) Although pregnancy and delivery cause changes of the relapse rate, they have no influence on mid and long term residual disability. 3) Breast-feeding and epidural analgesia do not seem to have any deleterious effect on the disease. 4) Lastly, MS does not seem to influence pregnancy, delivery or the child's health. The studies available to date suffer from methodological limitations. They need to be confirmed by prospective studies. This is the purpose of the study entitled "Pregnancy in multiple sclerosis, PRIMS", which has been carried out since 1992 at the European level.

Breast Feeding↗

Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group.

BACKGROUND AND METHODS: Multiple sclerosis often occurs in young women, and the effect of pregnancy on the disease is poorly understood. We studied 254 women with multiple sclerosis during 269 pregnancies in 12 European countries. The women were followed during their pregnancies and for up to 12 months after delivery to determine the rate of relapse per trimester and the score on the Kurtzke Expanded Disability Status Scale (range, 0 to 10, with higher scores indicating more severe disability). The relapse rate in each trimester was compared with the rate during the year before the pregnancy. The effects of epidural analgesia and breast-feeding on the frequency of relapse during the first three months post partum and the disability score at 12 months post partum were also determined. RESULTS: The mean (+/-SD) rate of relapse was 0.7+/-0.9 per woman per year in the year before pregnancy; it was 0.5+/-1.3 during the first trimester (P=0.03 for the comparison with the rate before pregnancy), 0.6+/-1.6 during the second trimester (P=0.17), and 0.2+/-1.0 during the third (P<0.001). The rate increased to 1.2+/-2.0 during the first three months post partum (P<0.001) and then returned to the prepregnancy rate. The mean Kurtzke disability score worsened by 0.7 point during 33 months of follow-up, with no apparent acceleration during the post-partum period. Neither breast-feeding nor epidural analgesia had an adverse effect on the rate of relapse or on the progression of disability in multiple sclerosis. CONCLUSIONS: In women with multiple sclerosis, the rate of relapse declines during pregnancy, especially in the third trimester, and increases during the first three months post partum before returning to the prepregnancy rate.

Adult↗

Purification and characterization of a new cystatin inhibitor from Taiwan cobra (Naja naja atra) venom.

Cobra cystatin, a new cysteine-proteinase inhibitor of the cystatin superfamily, was isolated from the venom of the Taiwan cobra (Naja naja atra) by affinity chromatography on S-carboxymethylpapain-Sepharose and reverse-phase chromatography. The venom contained two forms of the inhibitor, one of 11870 Da and the other of 12095 Da, as determined by MS, and pI values of 6.2 and 6.1. Cobra cystatin strongly inhibits cysteine proteinases of the papain family, but not calpain. Papain, cathepsin L, cathepsin B and cathepsin S are inhibited with Ki values of 0.19, 0.1, 2.5 and 1.2 nM respectively. The amino acid sequence of cobra cystatin shows that it is a Type 2 cystatin. The amino acid sequence is 73% identical with that of the cystatin in African-puff-adder (Bitis arietans) venom, with which it shares a unique six-residue insertion in a region opposite the reactive inhibitory site. Cobra cystatin is 25-42% identical with other Type 2 cystatins, the most closely related being the recently described human cystatin M, which also has a similar five-residue insertion starting at position 76 (chicken cystatin numbering). A molecular phylogenetic tree of 16 representative members of Family 2 cystatins was constructed by parsimony analysis; it suggests that snake cystatins, together with Tachypleus tridentatus (Japanese horseshoe crab) cystatin and human cystatin M, form a new subfamily within cystatin Family 2.

Amino Acid Sequence↗

Course of valvular strands in patients with stroke: cooperative study with transesophageal echocardiography.

BACKGROUND: Native valve strands might be related to the acute stage of thrombosis or might suggest a long-term valvular change. We aimed to estimate changes in the strands in patients with stroke through a serial transesophageal echocardiographic (TEE) study. METHODS AND RESULTS: A study was conducted among patients who were referred for TEE for stroke or cardiac pathology. Patients had TEE examinations with a 5-MHz multiplane TEE probe. Echocardiography was repeated 3 months later in patients with stroke. TEE was performed in 180 patients admitted to cardiology units and in 160 patients referred to neurology units. Among 34 patients with valvular strands, 30 were referred to neurology for stroke, whereas 4 patients were admitted to cardiology (18.8% versus 2.2%, difference 16.5%, 95% confidence interval 10% to 22.9%, P =.001). Strands were located on the mitral valve in 16 patients, the aortic valve in 6 patients, and both left heart valves in 8 patients. Among the 38 valves with strands, 17 (44. 7%) were morphologically normal, 4 (10.5%) were thickened, 7 (18.4%) were redundant, and 10 (26.3%) had both abnormalities. TEE showed other abnormalities in 16 (53.3%) patients, whereas 14 patients had only strands. Twenty-six (86.6%) patients had a second TEE study 3 months later. Strands were not found in 4 (15.4%) patients (95% confidence interval 4.3% to 34.9%). CONCLUSIONS: Valvular thickening or redundancy may predispose valves to strand formation. Native valve strands usually persist and thus reflect a chronic valvular change.

Adolescent↗

Headache in hypothyroidism. Prevalence and outcome under thyroid hormone therapy.

OBJECTIVE: To evaluate the frequency of headache in patients with hypothyroidism. DESIGN: A prospective study of a cohort of patients with hypothyroidism. SETTING: Outpatients or inpatients in a headache clinic and endocrinological clinic. PATIENTS: 102 adults, ages 35 to 78 (83F, 19M) experiencing clinical and biological hypothyroidism. RESULTS: Thirty-one patients with hypothyroidism of 102 (30%) presented with headache 1 to 2 months after the first symptoms of hypothyroidism. The headache was slight, nonpulsatile, continuous, bilateral, and salicylate responsive and disappeared with thyroid hormone therapy. CONCLUSION: The authors believe there is a prevalence of nonspecific headache in hypothyroidism and that it has a particular response to thyroid hormone therapy. Hypothyroidism is another cephalalgia with an endocrinological cause after menstrual cephalalgia. We suspect a metabolic or vascular pathophysiological process.

Adult↗

The interest of surgical closure of patent foramen ovale after stroke: a preliminary open study of 8 cases.

The risk of stroke and the risk of recurrent strokes in patients with patent foramen ovale (PFO) need a prevention that still remains a therapeutic problem. There are 4 preventive treatments: anti-agregants, anti-coagulants, transcatheter closure, and surgical closure of PFO. The aim of this study was to demonstrate that surgical closure of PFO is safe and useful for prevention of strokes. Eight patients with stroke and PFO diagnosed by transesophageal echography (TEE) were prospectively selected for surgical closure. It was necessary to be younger than 70 years, not to have another cause of stroke, and to have either recurrent strokes or several ischemic lesions on MRI, isolated for PFO associated with an atrial septal aneurysm, and to have a Valsalva maneuver or cough inducing the stroke. For these reasons, these patients were considered to be an homogenous group with a strong relationship between the PFO and the stroke, and with a high risk of recurrence of stroke. The 8 patients had a direct suture of the PFO with a cardiopulmonary bypass. All patients were followed-up with clinical, MRI and TEE examinations during 12 months after surgery. No surgical complications were observed. After one year, without any anticoagulant treatment, no recurrent stroke or transient ischemic attack, no new ischemic lesions on MRI, nor neuropsychological disturbance were noted. No post-surgical inter-atrial right-to-left shunting was observed. In the absence of controlled studies to guide therapeutic options, our data suggest that surgical closure of PFO in patients with stroke, is safe and efficacious to prevent recurrent stroke without any anticoagulants in the first year of follow-up. Further studies are needed to evaluate the long-term role of surgical closure of PFO as an alternative to prolonged anti-thrombotic treatment.

Adult↗

Epilepsy in patients with multiple sclerosis: radiological-clinical correlations.

PURPOSE: To determine potential mechanisms of epilepsy in patients with multiple sclerosis (MS). METHODS: Among 402 patients with clinically and radiologically defined MS, including de novo cases, presenting to the Neurology Service, University Hospital of Dijon, we identified 17 with epileptic seizures (4.25%). Among them, the percentage with partial seizures (50%) was greater than that in the reference population. RESULTS: In most of the patients with MS, plaques were localized in the frontal region, associated with frontal and callosal atrophy, a frontal syndrome, and severe disability status (as assessed by a standard scale). Magnetic resonance imaging (MRI) showed numerous subcortical plaques. Seizures generally were well controlled with antiepileptic drugs (AEDs). CONCLUSIONS: Our data suggest that the subcortical plaques of MS underlie seizure activity in patients with MS and epilepsy.

Adult↗

[Is it possible to predict the evolution of multiple sclerosis?].

Three characteristic features describe our understanding of the clinical course and outcome in multiple sclerosis: a validated statistical model of disease progression, wide interindividual variability, and a fixed rate of progression in an individual patient. However for and individual patient, it is still impossible to derive a precise and exact prediction of disease outcome, the only reliable method is the deterministic approach developed by Fog and Linneman in 1970 which consists in objective quantitative neurological examinations performed at three month intervals over several years in the same patient. In routine practice, this method in rather unrealistic. Bran MRI data with conventional techniques are also poorly discriminant. Conversely, it may be anticipated that new magnetic resonance techniques, more sensitive to axonal loss, demyelinization and gliosis, will provide reliable answers to this issue upon which therapeutic decisions depend.

Disease Progression↗

[A brachial form of motor neuropathy caused by lead poisoning].

We report the case of a 48-year-old patient who developed acute onset bilateral, peripheral motor dysfunction in the arms and forearms. Clinical history, electromyography and laboratory tests confirmed the diagnosis of peripheral neuropathy caused by lead poisoning from the domestic water supply. The EMG showed axonal alterations. Improvement was observed after treatments with chelating agents and removal of the source of poisoning. This case provides the opportunity to recall the traditional 1889 Dejerine classification of lead-related peripheral neuropathies and is a warning signal that lead poisoning remains a problem in peri-urban areas of developed countries.

Abdominal Pain↗

Kininogen-derived fluorogenic substrates for investigating the vasoactive properties of rat tissue kallikreins--identification of a T-kinin-releasing rat kallikrein.

Peptide substrates with intramolecularly quenched fluorescence that reproduce the rat kininogen sequences at both ends of the bradykinin moiety were synthesized and used to investigate the kinin-releasing properties of five rat tissue kallikreins (rK1, rK2, rK7, rK9, rK10). Substrates derived from rat H- and L-kininogen were cleaved best by rK1, especially that including the N-terminal insertion site of bradykinin, Abz-TSVIRRPQ-EDDnp(Abz = O-aminobenzoyl, EDDnp = ethylenediamine 2,4-dinitrophenyl), which was cleaved at the R-R bond with a k(cat)/Km of 12400 mM(-1) s(-1). Replacement of the P2' residue Pro by Val in Abz-TSVIRRPQ-EDDnp gave a far less specific substrate that was rapidly hydrolysed by all five rat kallikreins and human kallikrein hK1. Peptidyl-N-methyl coumarylamide substrates, which lack prime residues, also had low specificities. The importance of the P2' residue for rK1 specificity was further demonstrated using a human-kininogen-derived substrate that included the N-terminal insertion site of bradykinin (Abz-LMKRP-EDDnp). This was cleaved at the M-K bond by hK1 (kallidin-releasing site), but at the K-R bond (bradykinin-releasing site) by rK1. Competition experiments with Abz-TSVIRRPQ-EDDnp, which is resistant to most kallikreins, and Abz-TSVIRRVQ-EDDnp, a general kallikrein substrate, demonstrated that the former competitively inhibited hydrolysis by rK9 and hK1, with Ki values similar to the Km values for the substrate. Thus Pro in P2' does not prevent the peptide binding to the enzyme active site, but impairs cleavage of the scissile bond. The T-kininogen-derived substrate with the T-kinin C-terminal sequence (Abz-FRLVR-EDDnp) was cleaved by rK10 (k(cat)/Km = 2310 mM(-1) s(-1)) and less rapidly by rK1, rK7 and hK1, at the R-L bond, while that corresponding to the N-terminal (Abz-ALDMMISRP-EDDnp) of T-kinin was resistant to all five kallikreins used, suggesting that none has T-kininogenase activity. But this substrate was hydrolysed by a semipurified sample of submandibular gland extract. Another kallikrein, identified as kallikrein rK3, was isolated from this fraction and shown to hydrolyze Abz-ALDMMISRP-EDDnp; rK3 also specifically released T-kinin from purified T1/T2-kininogen after HPLC fractionation. Injection of purified rK3 and of Abz-ALDMMISRP-EDDnp-cleaving fractions into the circulation of anesthesized rats caused transient falls in blood pressure, as did purified rK1 but none of the other purified rat or human kallikreins. This effect occurred via activation of the kinin system since it was blocked by Hoe140, a kinin receptor antagonist.

Amino Acid Sequence↗

[Modelling of length of stay and costs in 2 homogeneous groups of hematological and pneumological patients: clinical characterization of patients with long-stay and high costs].

After the implementation of the Medicare Prospective Payment System (PPS) in the USA, many European countries like France have introduced DRGs to curb hospital overspending. However, there has been some reluctance from hospital actors, especially because of the heterogeneous nature of DRG's. To analyse this situation, we propose a method based on distribution modelization of length of stays and costs within DRGs. For each DRG, the model is based on a mixture of Poisson and Weibull distributions identified as subgroups. The subgroups are characterized by their means and their proportions which are estimated by maximization of data likelihood. For a particular DRG, the proportion of long stay or high-cost patients can be explained by the introduction of clinical variables in the model. First the model was applied to the DRG "leukemia and lymphoma" (HCFA V.3), using 133 discharge abstract files from the Dijon public teaching hospital which were classified into this DRG in 1993. Among the studies parameters only acute leukemia, neutropenia < 500 PNN/mm3, high dose aplastic chemotherapy, central venous catheterization, parenteral nutrition, use of protected or laminar air flow room, septicemia, large spectrum intravenous antibiotherapy, and blood transfusion had a significant influence on the distribution of the patients in the long stay or costly subgroup. Second, for DRG "chronic bronchopneumopathies" (n = 220) the significant parameters were mechanical ventilation, antibiotherapy, post hospitalization medicalized care.

Adolescent↗

[Nicotine and worsening myasthenia].

We report a case of myasthenia gravis worsened by a nicotine transdermal system, in a man who usually was smoking fourty cigarettes per day without any worsening of his symptomatology. He noted an increased bilateral ptosis, total ophtalmoplegia, difficulty in chewing and generalized weakness two hours after application of a nicotine transdermal system, the symptoms improving after he removed it. Cholinergic receptors involved in myasthenia gravis are nicotinergic, and their number at the neuromuscular junction is reduced in myasthenia gravis. That leads to a "functional overdosage" after application of the nicotine transdermal system similar to the cholinergic crisis. This case can be compared with myasthenia syndromes described during the Second World War in tobacco chewers without any muscle impairment.

Administration, Cutaneous↗