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Biomedical subjects

C Marchal

Publications and source records attributed to C Marchal.

At least 37 records · Page 2Linked to original sources

[Management of mucositis following radiotherapy for head and neck cancers].

Acute mucositis is common after radiotherapy for head and neck cancers. During the past 3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. At the present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxidants, Benzydamine hydrochloride), while others seem promising (Povidone-iodine, nonabsorbable antibiotic lozenges and antifungals, local GM-CSF, Glutamide, Low-energy laser, corticosteroïds). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or antifungal topicals (bicarbonates, Amphotéricine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal-sparing block, conformal radiotherapy and intensity-modulated radiation therapy).

Acute Disease↗

Casein kinase I-dependent phosphorylation within a PEST sequence and ubiquitination at nearby lysines signal endocytosis of yeast uracil permease.

Uracil uptake by Saccharomyces cerevisiae is mediated by the FUR4-encoded uracil permease. The modification of uracil permease by phosphorylation at the plasma membrane is a key mechanism for regulating endocytosis of this protein. This modification in turn facilitates its ubiquitination and internalization. Following endocytosis, the permease is targeted to the lysosome/vacuole for proteolysis. We have previously shown that uracil permease is phosphorylated at several serine residues within a well characterized N-terminal PEST sequence. In this report, we provide evidence that lysine residues 38 and 41, adjacent to the PEST sequence, are the target sites for ubiquitination of the permease. Conservative substitutions at both Lys(38) and Lys(41) give variant permeases that are phosphorylated but fail to internalize. The PEST sequence contains potential phosphorylation sites conforming to the consensus sequences for casein kinase 1. Casein kinase 1 (CK1) protein kinases, encoded by the redundant YCKI and YCK2 genes, are located at the plasma membrane. Either alone supports growth, but loss of function of both is lethal. Here, we show that in CK1-deficient cells, the permease is poorly phosphorylated and poorly ubiquitinated. Moreover, CK1 overproduction rescued the defective endocytosis of a mutant permease in which the serine phosphoacceptors were replaced by threonine (a less effective phosphoacceptor), which suggests that Yck activity may play a direct role in phosphorylating the permease. Permease internalization was not greatly affected in CK1-deficient cells, despite the low level of ubiquitination of the protein. This may be due to CK1 having a second counteracting role in endocytosis as shown by the higher turnover of variant permeases with unphosphorylatable versions of the PEST sequence.

Amino Acid Sequence↗

[Leukemia and pre-leukemic conditions occurring after treatment of breast cancer].

OBJECTIVE: The purpose of this study was to determine the clinical and prognostic features of leukemias and preleukemic states, whatever the mode of development, observed in patients after treatment of breast cancer. PATIENTS AND METHODS: A retrospective multicentric analysis was made of 121 patients treated for breast cancer and who later developed leukemia or a preleukemic state. Initially, 44 patients had undergone mastectomy, 72 had conservative surgery and 119 had locoregional irradiation. At least one chemotherapy session was performed in 90 patients and 48 had received tamoxifen. The risk of relapse of breast cancer was high, moderate or low for 44, 46 and 24 patients respectively (data not available for 7 patients). RESULTS: By class, the hematology diseases found were: myelodysplasia (n = 9), refractory anemia with blast excess (n = 7), acute lymphoblastic leukemia (n = 6), acute myoblastic leukemia (n = 93 including a majority of type 2 and type 4). For acute myeloblastic leukemia, mean delay to onset was 65 and 37 months respectively without and after chemotherapy. The prognosis of these cases of leukemia and preleukemic states was poor with an overall death rate of 86%. CONCLUSION: In light of the recent development of indications for adjuvant chemotherapy even for subgroups of patients at moderate risk, it is important to more precisely assess the absolute benefit in terms of survival compared with the risk of severe complications, particular secondary leukemia. In the future, a systematic registry and a case-control study are required.

Adult↗

Evaluation of left ventricular systolic function by 3D echocardiography: a comparative study with X-ray angiography and radionuclide angiography.

OBJECTIVE: the aim of this study was to evaluate left ventricular systolic function by 3D ultrasound as compared to with radionuclide and X-ray angiographies. METHODS: one hundred and four patients were examinated by 3D ultrasound (3D-US) but only 72 examinations were successful. Thirty patients were investigated by 3D-US, M-mode US or bidimensional (2D) US, and X-ray angiography (group I) and 42 patients were investigated by 3D-US, M-mode, or 2D, and radionuclide angiography (group II). RESULTS: the correlation between ejection fraction (EF) evaluated by 3D-US and reference methods was found to be good and similar for the two groups (r=0.75; P<10(-4) for group I and r=0.76; P<10(-4) for group II). The correlation between EF calculated by conventional 2D-US and by reference methods was lower (r=0.60; P=0.04 for group I and r=0.54; P=0.001 for group II). The correlation between EF evaluated by 3D- and 2D-US was modest (r=0. 55; P=0.001 for the whole group). The correlation between 3D-US left ventricle end-diastolic volume (EDV) and end-systolic volume (ESV) and those evaluated by X-ray angiography was also modest (r=0.33; NS for EDV and r=0.60; P<10(-4) for ESV). The correlations between EDV and ESV in 3D-US, and those evaluated from radionuclide angiography were fairly good and in the same range (r=0.76; P<10(-4) and r=0.87; P<10(-4)). CONCLUSION: the 3D-US system using a rotating probe in an apical view is valuable for evaluation of left ventricular systolic function.

Angiocardiography↗

Localization of the ventricular preexcitation site in Wolff-Parkinson-White syndrome with Doppler tissue imaging.

PURPOSE: The objective of this study was to evaluate the ability of Doppler tissue imaging (DTI) to localize the ventricular emergence site of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome). METHODS: Thirty-three patients were studied prospectively by Doppler tissue imaging (128XP and Sequoia 256 echocardiographic systems; Acuson, Mountain View, Calif) before investigation of Wolff-Parkinson-White syndrome and after radiofrequency ablation of the accessory pathways. The normal appearance of the ventricular contractions was defined in a group of 10 control subjects. The preexcitation zone was determined as a zone of maximum acceleration in "DTI acceleration mode" or as a coded contraction zone in "DTI velocity mode," at the time of the delta wave or before the onset of the QRS complex. RESULTS: The earliest ventricular activation site was correctly localized for 12 of the 15 left-sided pathways (8 anterior or anterolateral, 2 lateral or posterolateral, 2 inferior). When wall motion abnormalities were detected in the left ventricle by DTI, the left-sided localization was confirmed by electrophysiologic exploration. For the right-sided pathways, the localization was correct in only 4 of 11 cases (3 posteroseptal and 1 anterolateral). After effective ablation in all patients, the abnormalities corresponding to the electrophysiologic data disappeared totally in only 11 of 16 patients. CONCLUSION: In the presence of Wolff-Parkinson-White syndrome, DTI localizes contraction abnormalities associated with early activation of a part of the ventricle. However, the interpretation of the images remains difficult because the normal coding of the contraction of the ventricular walls depends on the incidence for which they are investigated. This noninvasive examination seems to be an effective tool for localizing the left-sided accessory pathways of the left ventricle, in particular in the anterior, anterolateral, or inferior walls.

Adult↗

Sarcoma after radiation therapy: retrospective multiinstitutional study of 80 histologically confirmed cases. Radiation Therapist and Pathologist Groups of the Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: To evaluate the best strategy for treatment of sarcoma that occurs after radiation therapy. MATERIALS AND METHODS: Records were retrospectively reviewed for 80 patients with a confirmed histologic diagnosis of sarcoma that occurred after radiation therapy performed during 1975-1995. The patients were treated for breast cancer (n = 33, 42%), non-Hodgkin lymphoma (n = 9, 11%), cervical cancer (n = 9, 11%), benign lesions (n = 4, 5%), or other tumors (n = 25, 31%). Sarcoma occurred after a mean latency of 12 years (range, 3-64 years), with most (70%) developing in the soft tissue. Treatment included surgery (28 patients), surgery and chemotherapy (18 patients), chemotherapy only (15 patients), and radiation therapy (14 patients). RESULTS: By the end of the study, 51 patients were dead, including 46 due to sarcoma. Median survival was 23 months. Overall survival rates at 2 and 5 years, respectively, were 69% and 39% for patients treated with surgery, 10% and 0% for those treated with chemotherapy, and 52% and 35% for those treated with surgery and chemotherapy (P =.001). The 2- and 5-year rates for survival without recurrence were 54% and 32%, respectively. CONCLUSION: The results confirm the beneficial effect of surgery. Further study is needed to explore the roles of combined treatments.

Adolescent↗

[Painless abducens palsy disclosed by spontaneous dissection of the intracavernous internal carotid artery].

A 63-year-old man presented suddenly and spontaneously an isolated painless oculomotor palsy of the nerve abducens. As no etiology could be suspected a head MRI was performed. It showed a T1 hypersignal of the intracavernous segment of the internal carotid artery with a double-lumen pattern typical of dissection. The patient was treated with aspirin and recovered from clinical symptoms in 10 weeks. A control MRI was performed 3 months after the onset of symptoms and showed the regression of the images of dissection. There was no ischemic lesion of the brain. This case underlines the diversity of the symptoms of spontaneous dissections of cervicocephalic arteries, especially absence of pain, palsies of cranial nerve that are not always limited to lower cranial nerve, and existence of dissections limited to the intracranial segment of the carotid artery. It suggests the interest of MRI in the diagnosis of isolated oculomotor nerve palsies.

Abducens Nerve Diseases↗

[Radioanatomy of the cerebral cortex. Practical guide of identification].

Cerebral sulci identification process is based on several formal rules: it consists a series of steps allowing the identification of the major sulci. The process may be variable for each of us and we propose to read the images in certain order starting with the frontal lobe and its superior frontal gyrus than precentral and central gyri followed by the lateral fissure. Then the insular, lateral parietal and medial hemispheric regions. Finally the major sulci within the temporal and occipital lobes are described in the frontal plane. This presentation indicates the principal rules of cerebral lobes'identification, the basis of variability perception and the localization of small lesions allowing an accurate correlation with clinical findings and a suitable therapeutic procedure.

Cerebral Cortex↗

In vivo potentiation of radiation response by topotecan in human rhabdomyosarcoma xenografted into nude mice.

The lack of new highly efficacious drugs for cancer treatment promotes the search for innovative therapeutic modalities. The authors reported the results leading to the definition of parameters needed to demonstrate a possible radiopotentiation by topotecan (TPT) on two representative human rhabdomyosarcomas (RMSs) xenografted into nude mice. Experimental studies of radiopotentiation with different doses of topotecan showed that concomitant association of topotecan and RT for 5 consecutive days provided a synergistic therapeutic effect. Response rates were statistically higher with the radiochemotherapeutic combination (P < 0.001). Efficacy enhancement factors of this combination compared with the sum of the antitumoral activity of these treatments separately administrated were 1.54 and 1.60, respectively, on both rhabdomyosarcomas. Moreover, the efficiency of the combination of radiotherapy at the dose of 20 Gy with topotecan (12.5 mg/kg) was not statistically different from that of radiotherapy at the dose of 40 Gy. According to microscopy results, the analyses performed at different periods after topotecan treatment alone, radiotherapy alone, and their combination seemed to show that tumoral repopulation by malignant cells is as fast as the dose of radiotherapy and/or topotecan is low. Furthermore, lesions observed with the dose of 40 Gy were similar to those obtained with the association of topotecan at the dose of 12.5 mg/kg and radiotherapy at the dose of 20 Gy. In conclusion, all clinical and pathological results are consistent with a radiopotentiation effect of topotecan on the two xenografted human rhabdomyosarcomas and are currently leading to the design of clinical studies.

Adolescent↗

[Cardiac abnormalities in a prospective series of 40 patients with type 2 diabetes].

Cardiovascular mortality, the principal cause of early death in diabetics, is multifactorial. A prospective study was undertaken to analyse the different factors of excess cardiac complications in 40 patients with type 2 diabetes, whatever the symptomatology, by making an inventory of the cardiac abnormalities (systolic and diastolic left ventricular function, left ventricular hypertrophy, abnormalities of myocardial perfusion, heart rate variability and arrhythmias). Patients underwent 24 hour Holter monitoring, high amplification signal averaged electrocardiography, echocardiography, Thallium scintigraphy with a dipyridamole test followed by coronary angiography when positive. Patients were aged 60 +/- 8 years, diabetics for 11.8 +/- 6.8 years, and had associated cardiovascular risk factors: 85% were obese, 75% were hypertensive, 62.5% had hypercholesterolaemia and 60% were smokers. The HbA1C was 9.2 +/- 19%. An increased left ventricular mass was observed in 34.2% of patients. The left ventricular ejection fraction was normal (59.1 +/- 6.8%); 69.7% of patients had left ventricular diastolic dysfunction. Reduced heart rate variability was observed in 51.8% of cases. Late ventricular potentials were recorded on high amplification signal averaging in 39.5% of patients; 25.6% had significant ventricular extrasystoles and 52.2% had atrial extrasystoles. Twelve patients (45%) underwent Thallium myocardial scintigraphy with a positive dipyridamole test, 8 of whom had coronary lesions on angiography. The excess cardiac complications of diabetes is mainly due to ischaemic heart disease aggravated by autonomic neuropathy, left ventricular diastolic dysfunction, arrhythmias and left ventricular hypertrophy. In future, larger series are required to demonstrate that this detection can guide therapeutic intervention and reduce cardiac morbidity and mortality of diabetics.

Adult↗

[The mesorectum: improvement and anatomy of a semantic error].

AIMS: The cancer of the rectum touches 10,000 patients per year in France. Its treatment is mainly surgical. 50% of the treated patients will die of their cancer, either by loco-regional recurrence, or by metastatic disease. The rates of local recurrence vary from 10 to 40%. Heald is first who brought back recurrence rates lower than 4%, results obtained by the only surgical treatment. This treatment included the total exeresis of cellulo-fatty tissue surrounding the rectum, tissue which was baptized mesorectum. The aims of this work is to define and describe this space, and to discuss its Christian name. MATERIAL AND METHODS: The anatomical study carries on the dissection of 2 frozen pelvis of fresh man, one cut transversely on the level of L4, the other half-compartment sagittaly, then defrosted for the dissection. RESULTS: The mesorectum is defined and its various structures, fascia, vessels and nerves, are detailed. CONCLUSION: The mesorectum is an anatomical and surgical structure individualisable. Its recognition and its importance were born from the understanding of the fascia and the rectal anatomy. Its exeresis decreases the rate of the local recurrence (18). The technique of exeresis of the mesorectum must be validated, standardized, in order to be reproducible in the treatment of the cancer of the rectum.

Female↗

Nine breast angiosarcomas after conservative treatment for breast carcinoma: a survey from French comprehensive Cancer Centers.

OBJECTIVES: To conduct a survey of the angiosarcomas developing after breast conservation for carcinoma in the French Cancer Centers, to study the evolution of these cases in detail, and to review literature in an attempt to propose an optimal treatment scheme. MATERIAL AND METHODS: Eleven of the 20 French Cancer Centers agreed to research and retrospectively analyze all angiosarcomas discovered in patients previously treated by conservative treatment. The majority of the patients were node negative, T1N0M0. The mean age of the patients at the time of primary breast cancer treatment was 62.5 years, and 69 years at the diagnosis of the angiosarcoma. RESULTS: During the last two decades, nearly 20,000 patients have been treated conservatively in these 11 centers, and only 9 cases of angiosarcoma were found. The median latency period between the treatment of the breast carcinoma and the diagnosis of the breast angiosarcoma was approximately 74 months, with a range of 57-108 months. Mastectomy was performed as the main treatment of this angiosarcoma. All recurrences after mastectomy for the angiosarcoma appeared within 16 months after the mastectomy. A median time of recurrence was found to be 7.5 months, regardless of the treatment. The angiosarcomas appeared to be very aggressive, and chemotherapy, radiotherapy, and sometimes hyperthermia could only palliate the condition for a short time. After the diagnosis of angiosarcoma, the median survival was 15.5 months, showing a particularly poor prognosis. Only 1 patient of 9 is alive without progressive disease at 32 months after salvage mastectomy for the recurrence of the angiosarcoma. Precise data obtained from 11 centers show that, of 18115 breast carcinomas treated conservatively, only 9 breast angiosarcomas are reported, which represents a prevalence of 5 cases of angiosarcoma per 10,000, which is the same prevalence for primary breast angiosarcomas occurring in healthy breasts. CONCLUSION: Angiosarcoma developing after breast conserving therapy for carcinoma is a rare event, and induction of it by treatment is controversial. However, early diagnosis is essential and it appears that radical mastectomy gives the highest chance of cure and the best long-term survival.

Age of Onset↗

[Alcohol and epilepsy].

Epileptic seizures occur in 5-15% of individuals drinking alcohol. The majority are related to withdrawal, after heavy drinking, but these seizures may be indicative of an underlying structural disease, and always need diagnostic investigations. This type of fit does not require long term anticonvulsant therapy. More than 20% of newly diagnosed epilepsies in adults are alcoholic epilepsies, which concern less than 10% of alcoholic patients. Post-traumatic epilepsy is frequently intricate. Long term anticonvulsant therapy may be indicated, but is only possible if abstinence is acquired. Rare syndromes have been described, which specificity has not been demonstrated. Excessive drinking may provoke seizures in epileptics, whereas moderate or occasional use of alcohol may be not detrimental.

Adult↗

[Comparative study of post-infarction myocardial viability after fibrinolysis by stress tomoscintigraphy and echography: can viability be detected without ischemia?].

The objectives of this prospective study was to define the comparative ability of stress myocardial scintigraphy and dobutamine stress echocardiography to demonstrate post-MI myocardial viability, assessed on the functional recovery in terms of improvement of global and segmental kinetics by cardiac gamma-angiography after revascularization. 18 patients (11 anterior MI, 7 lateral or inferior MI) and 162 segments were analysed semiquantitatively. All patients with persistent significant stenosis underwent secondary revascularization of the artery responsible for myocardial infarction. The prevalence of viability was high, as only 34% of segments initially presented a segmental kinetic abnormality and contraction was improved at 6 months in 54% of cases. Stress scintigraphy and dobutamine echocardiography detected viability with a sensitivity of 96% and 70%, a specificity of 88% and 82%, a positive predictive value of 89% and 77% and a negative predictive value of 95% and 76%, respectively. Only the wall score index with low-dose dobutamine was correlated with the ejection fraction at 6 months. Stress echocardiography is a more reliable predictor of the degree of functional recovery after revascularization. Scintigraphy visualizes much more extensive abnormalities than echocardiography. This often corresponds to ischaemic territories with normal contraction under baseline conditions and low doses of dobutamine. It therefore seems preferable both examinations for optimal assessment of thrombolized patients following myocardial infarction.

Adult↗

Trypanosoma brucei TBRGG1, a mitochondrial oligo(U)-binding protein that co-localizes with an in vitro RNA editing activity.

We report the characterization of a Trypanosoma brucei 75-kDa protein of the RGG (Arg-Gly-Gly) type, termed TBRGG1. Dicistronic and monocistronic transcripts of the TBRGG1 gene were produced by both alternative splicing and polyadenylation. TBRGG1 was found in two or three forms that differ in their electrophoretic mobility on SDS-polyacrylamide gel electrophoresis gels, one of which was more abundant in the procyclic form of the parasite. TBRGG1 was localized to the mitochondrion and appeared to be more abundant in bloodstream intermediate and stumpy forms in which the mitochondrion reactivates and during the procyclic stage, which possesses a fully functional mitochondrion. This protein was characterized to display oligo(U) binding characteristics and was found to co-localize with an in vitro RNA editing activity in a sedimentation analysis. TBRGG1 most likely corresponds to the 83-kDa oligo(U)-binding protein previously identified by UV cross-linking of guide RNA to mitochondrial lysates (Leegwater, P., Speijer, D., and Benne, R. (1995) Eur. J. Biochem. 227, 780-786).

Alternative Splicing↗

A PEST-like sequence mediates phosphorylation and efficient ubiquitination of yeast uracil permease.

Uptake of uracil by the yeast Saccharomyces cerevisiae is mediated by a specific permease encoded by the FUR4 gene. Uracil permease located at the cell surface is subject to two covalent modifications: phosphorylation and ubiquitination. The ubiquitination step is necessary prior to permease endocytosis and subsequent vacuolar degradation. Here, we demonstrate that a PEST-like sequence located within the cytoplasmic N terminus of the protein is essential for uracil permease turnover. Internalization of the transporter was reduced when some of the serines within the region were converted to alanines and severely impaired when all five serines within the region were mutated or when this region was absent. The phosphorylation and degree of ubiquitination of variant permeases were inversely correlated with the number of serines replaced by alanines. A serine-free version of this sequence was very poorly phosphorylated, and elimination of this sequence prevented ubiquitination. Thus, it appears that the serine residues in the PEST-like sequence are required for phosphorylation and ubiquitination of uracil permease. A PEST-like sequence in which the serines were replaced by glutamic acids allowed efficient permease turnover, suggesting that the PEST serines are phosphoacceptors.

Binding Sites↗

[Interstitial brachytherapy in infiltrating cancer of the bladder. The Nancy experience].

PURPOSE: From 1975 to 1996, 98 patients with infiltrative vesical carcinomas were treated at the Centre Alexis Vautrin by conservative surgery and interstitial brachytherapy (192lr). The mean follow-up was about eight years. From this retrospective non randomized study, we tried to determine the tolerance to this treatment. MATERIALS AND METHODS: There were 86 men and 12 women. The mean age was 63 years. We found three pTis tumors, 28 stage pT1 tumors, 38 stage pT2 tumors, 24 stage pT3A tumors, four stage pT3B tumors and one stage Tx tumors. The therapeutic scheme consisted of pelvic radiation therapy (3 fractions of 3,5 Gy) immediately followed by lymphadenectomy (for stage pT3 tumors) and by cystotomy or partial cystectomy during which we inserted brachytherapy plastic tubes. The delivered dose was 50 Gy for superficially infiltrative tumors and 30 Gy for deeply infiltrative tumors; at the lowest dose, the treatment ended with external beam irradiation. RESULTS: At 5 years the control rate was 72%, the specific survival 80% and the global survival 71%. Twenty-nine patients had a local recurrence. Of these, seven underwent total cystectomy. Thirty-seven patients developed 43 complications; 35 were intravesical, 10 (28%) were estimated to be higher than grade 2 because of technical problems that led us to modify the technique. CONCLUSION: It is essential to develop close collaboration between surgeons and brachytherapists, to select patients and to use a rigorous technique. Interstitial brachytherapy for infiltrative vesical carcinomas thus yields both high local control and satisfying results in regard to patient's well-being.

Brachytherapy↗