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Biomedical subjects

D Fontaine

Publications and source records attributed to D Fontaine.

At least 19 recordsLinked to original sources

Comparison of the epidermal growth factor receptor gene and protein in primary non-small-cell-lung cancer and metastatic sites: implications for treatment with EGFR-inhibitors.

BACKGROUND: Very recent studies have suggested that EGFR gene copy number and expression obtained by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) should be used to predict which lung cancer patients are expected to respond to anti-EGFR treatments. However, it is still not known whether EGFR expression differs in metastases compared to primary non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: EGFR status was analysed by IHC and FISH on tumor samples of primary NSCLC and at least one distant metastatic lesion in 30 patients. RESULTS: Ten cases (33.3%) showed primary tumor/metastasis discordance by IHC analysis (n = 30): in seven cases, EGFR was expressed in the primary tumor but not in the metastasis, while three samples showed EGFR expression in the metastasis but not in the primary tumor (Pearson correlation coefficient = 0.331, P = 0.0074). By FISH (n = 26), seven (27%) cases were discordant: six cases showed a high-level of EGFR polysomy in the primary tumor but not in the metastasis and one case showed a high-level of EGFR polysomy in the metastasis but not in the primary sample (Pearson correlation coefficient = 0.52, P = 0.007). CONCLUSION: EGFR expression is not stable during metastatic progression in a significant proportion of NSCLC. These findings have to be considered in future prospective studies.

Adult↗

[New surgical techniques for brain tumors].

During the past years, the development of new technologies and techniques has been applied to brain tumor surgery, leading to decreased surgical morbidity and increased efficiency. These techniques can be used to reduce the invasiveness of the surgical approach (endoscopy, neuronavigation, robotics), to improve guidance (stereotaxy, neuronavigation), to better identify the tumor limits (neuronavigation, metabolic imaging, intra-operative MRI) or the functional areas (functional imaging, electrophysiological functional mapping) to optimize resection and to respect eloquent areas. This article reviews these techniques, focusing on their respective principles, practical utility, impact and limits.

Brain Neoplasms↗

[French neurosurgical practice in neurooncology (national survey--part II). Census of current research protocols on brain tumors in France].

OBJECTIVE: This second part of the inquiry of the NeuroOncolgy Group of the French Neurosurgical Society was undertaken to evaluate the involvement of French neurosurgeons in brain tumor research. METHODS: In December 2003, A questionnaire called "Census of current and future research studies about brain tumors in your center" has been mailed to every French neurosurgical department. For each protocol, responders were asked to mention: the title of the protocol, its mono- or multi-centric design, the name of the principal investigator, the name of the neurosurgeon(s) involved in the study, the topic of the study (epidemiology, imaging, biology, genetics, therapy), tumor histology, financial support, and partners. RESULTS: Twenty-three centers responded. Sixty-three studies were described. There were 6 epidemiological studies, 7 imaging studies, 27 biological or genetic studies and 15 clinical trials concerning glial tumors, and 8 biological studies concerning non glial tumors. Each study is described in the text with the data previously mentioned. CONCLUSION: Despite the fact that several centers did not answer, this inquiry confirmed the strong involvement of French neurosurgeons in brain tumor research.

Brain Neoplasms↗

[Stabwound of the cervical spinal cord. Two case reports].

Two cases of Brown-Sequard syndrome following a stab wound of the cervical spinal cord are reported. Spinal cord hemisection was confirmed by magnetic resonance imaging and surgical exploration. Both patients presented leakage of the cerebrospinal fluid and underwent surgical repair. In the first case, the pia-mater was sutured to close the wound and decrease the risk of post-traumatic syringomyelia. Outcome at ten and two years follow up was good in both patients who were able to walk. One of them returned to work. The contribution of surgical repair of spinal cord stab wounds and mechanisms of recovery are discussed.

Adult↗

Long-term tolerability of tramadol LP, a new once-daily formulation, in patients with osteoarthritis or low back pain.

INTRODUCTION: Tramadol hydrochloride is a centrally acting analgesic, which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. An oral, once a day, sustained release formulation of tramadol is thought to be advantageous compared with immediate release preparations as it prevents plasma peaks associated with increased side-effects of the drug. It may also improve compliance. The purpose of the study was to assess the long-term safety of a new sustained-release formulation of tramadol (tramadol LP) in patients with knee or hip osteoarthritis and in patients with refractory low back pain. STUDY DESIGN: The design was a phase III, open, multicentre, international, tolerability study with tramadol LP at a dose titrated by the patient between 100 and 400 mg once daily, according to the intensity of pain. The treatment was administered for a continuous period of 4 weeks followed by an intermittent intake of 5 months in 204 patients. The safety criteria for evaluation were recording of adverse events, laboratory tests, electrocardiogram, radiography, global tolerability assessed by the patient and the investigators. RESULTS: Long-term use of tramadol LP was reasonably well tolerated. Most of the reported adverse events were expected and occurred within the first month of treatment. Roughly half of the patients (49%) reported adverse events, of which 66% were related to treatment. Gastrointestinal events (nausea and vomiting) were the most frequent. Serious adverse events were reported in 6.4% of patients, from which only two cases were related to treatment. There was no sign of tolerance development and the percentage of patients presenting withdrawal symptoms after the end of treatment was low (6%). CONCLUSION: Long-term treatment with tramadol LP once daily is generally safe in patients with osteoarthritis or refractory low back pain.

Acetaminophen↗

First-line nitrosourea-based chemotherapy in symptomatic non-resectable supratentorial pure low-grade astrocytomas.

At the present time, there are no proven beneficial effects of chemotherapy (CT) for the treatment of pure low-grade astrocytomas. Brain radiotherapy (RT) still remains the standard treatment in order to reduce or delay tumor progression or symptoms, despite possible long-term neurologic complications. We report 10 patients, with histologically proven pure low-grade fibrillary astrocytomas, to which we administered a first-line nitrosourea-based CT. All patients were symptomatic with pharmaco-resistant epilepsy or neurologic symptoms, and had been rejected for neurosurgical resection. All patients with epilepsy had a clinical improvement with reduction in seizure frequency and 60% became seizure-free. CT was well tolerated; all patients developed myelosuppression with 40% of grade III/IV hematotoxicity. Seven were alive at the time of writing with a mean follow-up of 6.5 years (3.5-12) from first recorded symptoms. The three deceased patients died 7.5, 7.5, and 8.5 years from first symptoms. These results demonstrate that some patients with symptomatic non-resectable fibrillary low-grade astrocytomas can be treated with up-front CT to improve their neurologic status. This report suggests that benefits of CT on symptoms, survival, and quality of life should be prospectively compared with RT.

Adult↗

Successful resection of a left insular cavernous angioma using neuronavigation and intraoperative language mapping.

Despite recent literature advocating the surgical removal of symptomatic Cavernous Angiomas (CA), even in critical brain areas, very few observations of insular CA surgery have been described, particularly in the left hemisphere. We report the case of a successful resection of a CA located in the dominant insula, using both neuronavigation and intra-operative functional mapping. This 33-year-old right-handed man harbored a left insular CA, revealed by generalized seizures following a bleed confirmed on MRI. The preoperative examination was normal. A stereotactic-guided surgery was performed under local anesthesia, with intra-operative functional mapping using direct cortico-subcortical electrical stimulation in the awake patient--allowing the surgeon to achieve total resection of both CA and pericavernomatous gliosis, as shown on repeated postoperative MRIs. There was no postsurgical deficit, nor any seizure without treatment (follow-up: 4.5 years). The diagnosis of CA was confirmed by histological examination. Taking account of the risk of morbidity due to the natural history of CA, particularly in eloquent brain regions, we suggest to routinely consider the possibility of a surgical treatment in cases of symptomatic (left dominant) insular CA, using combined intra-operative anatomical and physiological localization methods.

Adult↗

Long-term outcome of oligodendrogliomas.

BACKGROUND: Favorable prognostic factors for oligodendroglial tumors include age younger than 40 years, low tumor grade, and extent of resection. OBJECTIVE: To assess survival time and prognostic factors of 100 patients with oligodendrogliomas diagnosed between 1995 and 2002. METHODS: The tumors were rated histologically by the WHO classification as low grade (grade II) or anaplastic (grade III). One hundred patients were categorized into three groups: group A: grade II, group B: secondary grade III (low grade with anaplastic transformation during the follow-up), group C: de novo grade III. All patients were symptomatic at presentation and underwent neurosurgical procedure for histologic diagnosis. Follow-up was performed with clinical assessment, brain MRI, and MIBI scintigraphy. RESULTS: There were 66 men and 34 women (mean age at diagnosis 46.7 years). The most common first symptom was partial epileptic seizure (75%). Fifty-six patients had initial gadolinium enhancement (A: 15.6%; B: 36.8% as grade II, 95% as grade III; C: 90%), generally associated with MIBI hypermetabolism (p < 0.0001). Survival rates at 2, 5, and 10 years were A: 88%, 88%, 85%; B: 79%, 64%, 42%; C: 43%, 16%, 15%. CONCLUSIONS: Secondary anaplastic oligodendroglioma patients were younger than patients with de novo anaplastic oligodendrogliomas. Histologic confirmation is mandatory because some low grade oligodendrogliomas had gadolinium enhancement on MRI and some anaplastic did not. Survival time was longer for secondary than for de novo anaplastic oligodendrogliomas without difference in the duration of the malignant phase of the disease.

Adolescent↗

[Neoadjuvant chemotherapy for symptomatic non operable grade II fibrillary astrocytoma in adults].

We collected 6 case-reports of symptomatric non removable low grade fibrillary astrocytoma of adults treated with a procarbazine-CCNU-vincristine chemotherapy regimen. All patients had drug-resistant epilepsy but brain imaging was stable. Total gross resection was rejected because of Volume or tumor location. After 4 to 7 cycles of chemotherapy, 2 patients had partial response and one minor response on brain MRI. All of them were seizure-free. Progression free survival was not reached at 5 Years. Up-front chemotherapy for low-grade astrocytomas may be useful and has to be prospectively evaluated.

Adult↗

Body motion capture for activity monitoring.

CEA-LETI has developed a 3D orientation tracker based on accelerometers and magnetometers. Owing to an efficient data fusion algorithm, the tracker provides accurate 3D orientation angles. The tracker is small enough to be used as a wearable device and therefore is an interesting tool for body motion capture. Investigations are being performed to analyse how activity of a person can be monitored from body motion measured with the tracker. In the domain of healthcare monitoring, many applications are envisaged such as rehabilitation with 3D body motion capture, elderly dependency evaluation, context acquisition for physiological monitoring.

Activities of Daily Living↗

5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium.

PURPOSE: In the prostate testosterone is converted to the more potent androgen dihydrotestosterone by the enzymes 5alpha-reductase (5alphaR) types 1 (5alphaR1) and 2 (5alphaR2). Since 5alphaR2 is the dominant prostatic enzyme, the 5alphaR2 selective inhibitor finasteride has been widely used to treat benign prostatic hyperplasia (BPH). However, inhibition of both 5alphaR enzymes provides a greater decrease in serum dihydrotestosterone. We developed a specific antibody to 5alphaR1 and assessed expression in BPH and prostate cancer (pCa) tissue. The presence of this isoenzyme in localized prostate cancer would provide a rationale for assessing the efficacy of dual inhibition for prostate cancer prevention. MATERIALS AND METHODS: A polyclonal antibody to 5alphaR1 was developed and validated using 5alphaR1 and 5alphaR2 transfected COS-1 cells. A total of 26 BPH and 53 pCa specimens were assessed for 5alphaR1 protein expression using immunocytochemical methods. Also, 29 BPH and 37 pCa specimens were assayed for 5alphaR1 and 5alphaR2 enzyme activity. RESULTS: Specificity of the 5alphaR1 antibody was confirmed using transfected COS-1 cells. Cells transfected with 5alphaR1 showed specific staining in immunocytochemistry experiments and on Western blotting of cell lysates the expected 24 kDa band was observed. High intensity immunoreactivity for 5alphaR1 was observed in the tumor epithelium of 28% of pCa specimens. No high intensity epithelial staining was observed in BPH specimens. In 19% of pCa and 7% of BPH specimens 5alphaR1 enzyme activity was detected. CONCLUSIONS: The presence of increased 5alphaR1 in some prostatic malignancies suggests that it is worthwhile to investigate the use of a dual 5alphaR inhibitor to prevent or treat early stage prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Endovascular treatment of ruptured intracranial aneurysms in patients aged 65 years and older: follow-up of 52 patients after 1 year.

BACKGROUND AND PURPOSE: We sought to describe the clinical outcome and results obtained in the endovascular therapy of ruptured cerebral aneurysms in the elderly over an 8-year period. We compared endovascular therapy results in patients aged > or =65 and <65 years. METHODS: During 1993-1999, 52 patients aged 65 to 85 years (mean age, 71.5+/-4.7 years) were embolized with the use of Guglielmi detachable coils (group I). During the same period, 143 patients aged <65 years (mean age, 47+/-11 years) with ruptured cerebral aneurysm were treated with the same technique (group II). A clinical assessment was made on admission with the Hunt and Hess (HH) classification and again in the 12th month with the Glasgow Outcome Scale (GOS), with arteriographic control in months 3 and 12. RESULTS: In group I, clinical grades on admission were as follows: HH 1, 9.5%; HH 2, 33%; HH 3, 21%; HH 4, 34.5%; HH 5, 2%. Outcome was favorable in 48% of patients (GOS 1 or 2); the mortality rate was 23%. No rebleeding was observed. Patients presenting lesions > or =10 mm had an unfavorable outcome in >77% of cases. Thromboembolic complications were present in 13% of cases. In group II, clinical grades on admission were as follows: HH 1, 14.5%; HH 2, 47%; HH 3, 11%; HH 4, 24%; HH 5, 3.5%. Favorable outcome (GOS 1 or 2) was observed in 77% of cases, with 14% mortality. Complications due to the endovascular procedure were present in 4.2% of cases. Patients with HH grades 1 or 2 on admission showed a positive outcome (GOS 1 or 2) in 77% of cases in group I and in 88.5% of cases in group II. Mortality was 9% in the first subgroup compared with 2.8% in the second. Patients who had a high clinical grade on admission (HH 4 or 5) showed a favorable outcome (GOS 1 or 2) in 16% of cases in group I compared with 41% in group II. CONCLUSIONS: Endovascular treatment of ruptured intracranial aneurysms in patients aged > or =65 years appears to be effective against rebleeding and represents an alternative to surgery. However, perioperative thromboembolic complications are more frequent in the elderly population.

Adolescent↗

[Evaluation of measles, mumps and rubella vaccine coverage in 3 year old children in twelve French counties. Time-trends and related factors].

BACKGROUND: The aims of our study were to estimate the measle-mumps-rubella (MMR) vaccine coverage in 3 years old children in 12 French countees, to document the evolution between 1997 and 1999 in two groups of 6 countees (pilot group and control group) before and after the implementation of promotion programmes in the pilot group, and to identify factors related to measle-mumps-rubella vaccination. METHODS: Two telephone surveys were carried out in 1997 and 1999 among children randomly selected in the birth rolls of 12 French countees. Parents of 3 years old children were interviewed on measle-mumps-rubella vaccination, knowledge and opinions on vaccinations, utilisation of health care and socio-demographic characteristics. RESULTS: The participation rate was 97% in both surveys. Among the 7382 respondent parents, 98% had immediate access to the child's medical file and could document the vaccine status. The vaccine coverage did not increase significantly between 1997 and 1999 (86.7% versus 87.2%), both in control (89.3% vs. 90.2%) and pilot groups (84.3% vs. 84.3%). A logistic regression model showed that several factors were independently and significantly related to measle-mumps-rubella vaccination (utilisation of homeopathic medicines, mother's age, number of children, physician speciality (general practitioner or pediatrician) and opinion on vaccinations). CONCLUSION: Our study shows that there is a stagnation of vaccine coverage in several French countees, which makes unlikely the national objective of viruses eradication. This epidemiological situation makes very likely outbreaks of measles, mumps and rubella in these countees. National and local pilot programmes did not succeed to promote vaccination in countees with a low measle-mumps-rubella vaccine coverage. Our study identified sub-groups of parents who should be targeted by promotion programmes.

Adult↗

Magnetic resonance-guided stereotactic biopsies: results in 100 consecutive cases.

BACKGROUND: We present the results of 100 consecutive magnetic resonance (MR)-guided biopsies in cases where computerised tomography (CT) guiding was considered dangerous or impossible. METHOD: MR guiding was preferred to CT guiding for cases where lesions were located in the central area, or were not clearly visible on CT scan, or where the visualization of vessels was considered necessary. For most of the patients, calculation of target co-ordinates was performed using dedicated software enabling trajectory previsualization. There were 62 cases of contrast enhanced lesions, 32 cases of lesions without contrast enhancement, and 6 cases of very small lesions appearing hyperintense on T2-weighted images. FINDINGS: Biopsies allowed a histological diagnosis in 92 cases. In 8 cases, the biopsy was negative (necrosis, gliosis or normal brain tissue). Three patients had a transient worsening of their neurological disturbances. Two patient had a non-regressive loss of motor function. No patient died. INTERPRETATION: MR guiding for stereotactic biopsies was effective for CT-invisible or ill-defined lesions, lesions located in functional or densely vascularized areas and in the brain stem. The rate of postoperative complications was equivalent to or less than that reported in series of CT-guided biopsies.

Adult↗

Efficacy of continuous insufflation of oxygen combined with active cardiac compression-decompression during out-of-hospital cardiorespiratory arrest.

BACKGROUND: During experimental cardiac arrest, continuous insufflation of air or oxygen (CIO) through microcannulas inserted into the inner wall of a modified intubation tube and generating a permanent positive intrathoracic pressure, combined with external cardiac massage, has previously been shown to be as effective as intermittent positive pressure ventilation (IPPV). METHODS: After basic cardiorespiratory resuscitation, the adult patients who experienced nontraumatic, out-of-hospital cardiac arrest with asystole, were randomized to two groups: an IPPV group tracheally intubated with a standard tube and ventilated with standard IPPV and a CIO group for whom a modified tube was inserted, and in which CIO at a flow rate of 15 l/min replaced IPPV (the tube was left open to atmosphere). Both groups underwent active cardiac compression-decompression with a device. Resuscitation was continued for a maximum of 30 min. Blood gas analysis was performed as soon as stable spontaneous cardiac activity was restored, and a second blood gas analysis was performed at admission to the hospital. RESULTS: The two groups of patients (47 in the IPPV and 48 in the CIO group) were comparable. The percentages of patients who underwent successful resuscitation (stable cardiac activity; 21.3 in the IPPV group and 27.1% in the CIO group) and the time necessary for successful resuscitation (11.8 +/- 1.8 and 12.8 +/- 1.9 min) were also comparable. The blood gas analysis performed after resuscitation (8 patients in the IPPV and 10 in the CIO group) did not show significant differences. The arterial blood gases performed after admission to the hospital and ventilation using a transport ventilator (seven patients in the IPPV group and six in the CIO group) showed that the partial pressure of arterial carbon dioxide (PaCO2) was significantly lower in the CIO group (35.7 +/- 2.1 compared with 72.7 +/- 7.4 mmHg), whereas the pH and the partial pressure of arterial oxygen (PaO2) were significantly higher (all P < 0.05). CONCLUSIONS: Continuous insufflation of air or oxygen alone through a multichannel open tube was as effective as IPPV during out-of-hospital cardiac arrest. A significantly greater elimination of carbon dioxide and a better level of oxygenation in the group previously treated with CIO probably reflected better lung mechanics.

Adolescent↗

[Treatment of central and neuropathic facial pain by chronic stimulation of the motor cortex: value of neuronavigation guidance systems for the localization of the motor cortex].

Thirty two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27. 3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and nine of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the 3 patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localization and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

Adult↗

Intramedullary cavernous angioma. Resection by oblique corpectomy.

BACKGROUND: Intramedullary cavernomas are rare lesions usually operated on via a posterior approach and myelotomy. CASE REPORT: A 42-year-old woman progressively developed a tetraplegia with sphincter disturbances over a period of 26 years. Magnetic resonance imaging showed a cervical intramedullary cavernoma with an extramedullary anterolateral exophytic portion. To avoid myelotomy, this lesion was approached directly via its anterior exophytic portion. Through a cervical anterolateral approach, the vertebral body of C4 and the intervertebral discs were obliquely drilled out. The posterior longitudinal ligament and the dura mater were opened. The exophytic portion was coagulated and the intramedullary portion was completely excised. The dura mater was closed and a bone graft was inserted between C3 and C5 and secured with a plate. RESULTS: After transient worsening, upper limb weakness improved from its preoperative status but paraparesis persisted after a follow-up of 12 months. The sphincter disturbances disappeared. CONCLUSIONS: The anterolateral approach combined with oblique corpectomy may be an appropriate technique in case of anterior intramedullary cavernomas. It provides direct access to the lesion, avoiding additional myelotomy.

Adult↗

Absence of nitrate tolerance after long-term treatment with ramipril: an endothelium-dependent mechanism.

To determine whether nitrate tolerance is attenuated on aortas isolated from rats treated in the long term with an angiotensin-converting enzyme (ACE) inhibitor, five groups of rats were studied in parallel. Group 1 received ramipril, 1 mg/ kg/day, p.o., for 6 weeks; group 2 received ramipril at the same dose for 4 weeks, and the last 2 weeks, a cotreatment with ramipril plus HOE 140 (a bradykinin B2 antagonist, 500 microg/ kg/day, s.c. injections); group 3 received losartan, 2 mg/kg/day, p.o., for 6 weeks; group 4 received losartan at the same dose, and the last 2 weeks, a cotreatment with losartan plus HOE 140; and group 5 served as control. Rings of thoracic aorta from these groups were studied in organ baths. After nitroglycerin preincubation (10 microM for 30 min) in vitro, the dose-response curves to nitroglycerin were significantly shifted to the right in the control group but not in group 1. This protective effect was partially present in group 3; it was completely abolished in groups 2 and 4. In groups 1 and 3, it also was abolished after nitric oxide synthase (cNOS) inhibition (L-NMMA incubation) or removal of the endothelium. Superoxide anion accumulation (assessed by lucigenin chemiluminescence) was increased by nitroglycerin incubation in the control group but not in groups 1 and 3. After in vivo exposure to nitroglycerin (50 mg/kg subcutaneously twice daily for 4 days), this protection against nitrate tolerance also was observed in groups 1 and 3. Thus long-term ACE inhibition prevents nitrate tolerance by an endothelium-dependent mechanism involving mainly an enhanced NO availability via B2-kinin receptor. This effect on the cNOS pathway seems to attenuate the superoxide anion accumulation induced by nitroglycerin exposure (probably via a downregulation of oxidative enzyme).

Adrenergic beta-Antagonists↗