Biomedical subjects
Publications and source records attributed to J P Guichard.
We report water diffusion abnormalities in periventricular areas in a patient with Wernicke's encephalopathy. The reduction in diffusion disappeared after 2 weeks of treatment with intravenous thiamine. We suggest that the restricted mobility of cerebral water is related to inflammatory lesions.
Tresperimus (Cellimis), a new immunosuppressive agent, is mainly eliminated in the rat through metabolism, in which the oxidative deamination of the primary amine of the drug plays a major role. We have previously demonstrated in vivo the significant involvement of semicarbazide-sensitive amine oxidase (SSAO) in this reaction. Rat aorta, a tissue with one of the highest specific SSAO activities, was tested as a new in vitro model to elucidate tresperimus metabolism, using a combination of liquid chromatography/mass spectrometry (LC/MS) and high-performance liquid chromatography (HPLC) analyses. The metabolites resulting from the main metabolic pathway of the drug were formed in rat aorta homogenates. The use of various SSAO, lysyl oxidase and monoamine oxidase inhibitors confirmed that SSAO is predominantly involved in the main site of tresperimus metabolism but also in every metabolic pathway of the drug, including deamination of tresperimus metabolites M3 (desaminopropyl derivative of tresperimus) and M6 (guanidinohexylamine). A microsomal fraction of the rat aorta was used to characterize tresperimus deamination. The moderate affinity of membrane-bound SSAO for tresperimus, with a Km value of 66 microM, was counterbalanced by a catalytic efficiency superior to that of certain physiological substrates of SSAO, such as methylamine. The rat aorta provided an interesting model with which to study tresperimus metabolism, highlighting the important role that SSAO could play as a phase I oxidative enzyme in the metabolism of certain exogenous amines at the vascular level.
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Aneurysmal bone cysts are vascular lesions that destroy and expand bone. We report a recently treated case of an aneurysmal cyst of the sphenoid bone. A 14-year-old girl presented with frontal headaches, bouts of nausea, and vomiting. Computed tomography and magnetic resonance imaging showed typical features of an aneurysmal bone cyst. Arterial embolization was undertaken before surgery. The endoscopic transnasal procedure used allowed the complete removal of the aneurysmal bone cyst. This use of minimally invasive surgery makes this case of interest to surgeons of the skull base and sinuses.
The metabolism of tresperimus, a new immunosuppressive agent, was investigated in vivo and in vitro in rat and in human. Two metabolic pathways were identified at each side of the molecule with two deamination reactions on the spermidine moiety and hydrolysis of the amide bond leading to the liberation of guanidinohexylamine. As the major metabolic pathway of the drug seemed to be the oxidative deamination, the capacity of different amine oxidases to metabolize tresperimus was then tested using in vivo experiments in rat and in vitro studies in rat and human plasma. The increase of tresperimus plasma levels induced by the administration of hydralazine, an irreversible in vivo inhibitor of semicarbazide-sensitive amine oxidase (SSAO), reflected the major involvement of this enzyme in tresperimus metabolism. This result was confirmed in vitro in rat and human plasma by the use of semicarbazide, a specific SSAO inhibitor. As opposed to rat plasma, human plasma may be an interesting in vitro model to study the metabolism of a drug extensively metabolized by SSAO such as tresperimus. Indeed, SSAO activity was significantly higher in human plasma than in rat plasma. The second metabolic pathway of the drug, which only occurred in rat plasma, appeared thus as the major route of tresperimus metabolism in this biological matrix.
We point out the interest of computed tomographic reconstructions from spiral acquisition--particularly sagittal reconstructions--in the study of middle ear anatomy and adjacent structures: the facial canal and the chorda tympani. The reference reconstructions are axial and coronal reconstructions. So, we demonstrate the superiority of sagittal reconstructions for the visualization of the lateral process of the malleus, the body and long process of the incus, the third portion of the facial canal, and the chorda tympani. For the other structures of the middle ear and the other parts of the facial canal, these sagittal reconstructions are complementary. Besides, the best type of reconstruction to visualize the stapes and the vestibular window is the axial plane parallel to the stapes axis.
OBJECTIVE: The aim of this study was to analyze the natural history of arteriovenous malformations by reviewing 200 consecutive cases observed in all localizations between 1992 and 1996 in a multidisciplinary angioma clinic. PATIENTS AND METHODS: Files concerning 200 arteriovenous malformations were reviewed with a standardized observation sheet applying the severity criteria defined by the International Society for the Study of Vascular Anomalies. We used the Schobinger staging system which includes 4 grades of severity: grade I=dormancy, grade II=expansion, grade III=destruction, grade IV=cardiac decompensation. RESULTS: There was no predominance by gender. Cephalic localizations were the most common. The malformation was present at birth as indicated by history taking in 40 p. 100 of the cases. Progression during childhood (grade II) was observed in 84 p. 100. At the first consultation, the patients generally were more often in grade II than in grade I or III. Bone destruction was observed in 3 cases, signs of cardiac decompensation in 5. Arteriovenous malformations were part of a more complex syndrome in 9 cases. We noted a flare-up in the prepuberty or puberty period in 75 p. 100 of the cases and the possible role of puberty (64 cases), trauma (39 cases) and pregnancy (25 p. 100 of the adult women). Explorations were generally completed (Doppler, arteriography) by grade II, expressing the need for a map of expanding lesions. Finally it was difficult to assess posteriorly the beneficial or deleterious effect of the often multiple treatments prescribed for these patients. DISCUSSION: The review of these 200 cases pointed out the "pediatric" nature of the problem of arteriovenous malformations in the large majority of the cases and the often misleading presentation of these vascular anomalies, particularly grade I malformations. A false aspect of capillary malformation could raise the risk of inappropriate treatment. This review also confirmed known factors of exacerbation (puberty, pregnancy, trauma) and demonstrated the severity of these vascular anomalies which can progress with loco-regional expansion and invasion without a cellular proliferation component. The analysis of treatments used showed that embolization alone cannot definitively and totally control a superficial arteriovenous malformation and that no one treatment, even combined embolization and large excision, can be a guarantee to provide total cure.
The rationale for, and development of, a new suprabioavailable fenofibrate tablet formulation is described. The new suprabioavailable tablet formulation combines well-established micronisation technology with a new micro-coating process. The new formulation provides more predictable and reliable drug absorption. Owing to the strong relationship between the fenofibrate dissolution performance and its oral bioavailability, equivalent plasma levels of active principal are achieved at a lower dose, with less inter-subject variability and a reduced food effect. The new suprabioavailable tablet may, therefore, be a more efficient and better tolerated formulation.
The proximal internal carotid artery is most commonly spared in cerebral fibromuscular dysplasia. The authors report the cases of three young black patients with stroke and carotid megabulbs with fibrous components, two of whom had superimposed thrombi.
Deep cerebral venous thrombosis (DCVT) is a rare, potentially fatal disease. We carried out a retrospective analysis of eight patients presenting with DCVT, using CT and MRI data. Digital subtraction angiography (DSA), MR angiography (MRA) (2D phase-contrast), and angiography were performed in four, four and two patients, respectively. Direct (venous abnormalities) and indirect (parenchymatous involvement) signs of thrombosis were assessed. Follow-up MRI and MRA were performed on two patients. CT was initially normal in two patients, demonstrated a "cord sign" in deep veins in five and deep venous infarcts in three. When performed within a week of admission (seven patients), MRI showed thrombosis as into intense or high signal in deep veins on sagittal T1-weighted spin-echo images in all patients, and on axial T2-weighted spin-echo images in two. Deep venous infarcts were found in five patients. Direct or indirect signs of sagittal or lateral sinus thrombosis were present on CT in two patients and on MRI in five. CT angiography, MRA and DSA were concordant with MRI findings. CT venography showed persistent flow in thrombosed veins. MRI follow-up demonstrated progressive deep venous recanalisation.
Oesclim (Laboratoires Fournier, Dijon, France), also known as Esclim or Esclima, is a new estradiol transdermal delivery system (TDS) developed for the treatment of menopausal vasomotor symptoms. This open, randomized, three-way crossover study compared in 24 healthy postmenopausal women the pharmacokinetics of estradiol after a single 4-day application of Oesclim 50, Oesclim 100, and Vivelle 0.05 (CibaGeneva Pharmaceuticals, Summit, NJ; known as Menorest 50 in Europe, Rhône-Poulenc Rorer) on the upper buttock. Serum estradiol concentrations were determined by a validated radioimmunoassay method from samples taken before and during each TDS application. The concentration-time profiles for Vivelle 0.05 and Oesclim 50 were comparable with a similar absorption rate, giving a maximum concentration (Cmax) of 49 and 53 pg/mL above baseline, respectively, followed by a plateau throughout the 96-hour application period. At the end of this period, mean corrected estradiol concentrations were 18 and 19 pg/mL, respectively. The estradiol serum concentrations obtained after an application of Oesclim 100 were approximately twice as high than with Oesclim 50. All products were well tolerated, but skin intolerance was more frequent with Vivelle 0.05 (4 patients; four reports) and Oesclim 100 (3 patients; three reports) than with Oesclim 50 (none). Problems of imperfect adhesion were more than five times as frequent with Vivelle 0.05 (44%) than with Oesclim (8%).
OBJECTIVE: The aim of this study was to characterize the MR findings of various intracranial lesions in the central nervous system (CNS) tuberculosis. MATERIALS AND METHODS: The MRI findings (T1, T2 and T1 sequence after contrast) of 12 proved cases (10 males, 2 females, 24 to 64 years old, average: 35) of CNS tuberculosis were reviewed; 4 patients were seropositive for HIV. RESULTS: Several types of lesions were identified: tuberculomas called miliary lesions if they were smaller than 2 mm in diameter (7 cases), in 1 case the tuberculoma was revealed by two large lesions and bi-hemispheric localisations, leptomeningitis (5 cases), infarction (4 cases), abscesses (3 cases with solitary lesions in 2/3 cases), hydrocephalus (3 cases), pachymeningitis (2 cases). A tuberculomas-leptomeningitis association was found in 4 patients. The pachymeningitis form had an unusual aspect in one case. Patients with leptomeningitis showed thick meningeal contrast enhancement involving all basal cisterns, expanding to the sylvian fissures level, and causing narrowing of the sylvian arteries. Massive infarctions resulted from arterial englobement or embols. In three out of five patients, leptomeningitis was the initial presentation. In seropositive patients, tuberculosis was severe with high mortality (3/4 patients), and associated with other multiple lesions. CONCLUSION: Central nervous system tuberculosis has different appearances, mostly tuberculomas and leptomeningitis. MR with contrast is necessary for follow-up during treatment.
Cerebral amyloid angiopathy (CAA) is frequent but often asymptomatic. It can induce lobar haemorrhage, rapidly progressive dementia or recurrent transient neurological symptoms, other presentations being less frequent. We report 3 patients in their sixties presenting with a space occupying lesion which was the first manifestation of CAA. They were operated with a diagnosis of cerebral tumour. In all three cases, macroscopy was similar, the lesions were superficial in the cerebral cortex and the preoperative diagnoses were glioblastoma, meningioma and cavernoma. Histologically, the lesions consisted of a large inflammatory granuloma with numerous lipophages and siderophages surrounding capillaries with prominent endothelial cells. Vessels in the near cortex and meninges and within the granuloma harboured heavy amyloid deposits immunolabelled by anti-P component, anti-protein beta A4 with a A40 predominance and anti-apolipoprotein E. Adjacent cerebral cortex showed reactive gliosis and rare senile plaques. Amyloidosis is rarely considered among diagnoses of space occupying lesions. In our three cases, CT scan and MRI changes were related to the presence of an inflammatory granuloma around foci of haemorrhage and amyloid laden vessels.
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In an 18-month period, 3 cases of sphenoidal mucocele following pituitary surgery were diagnosed at our institution. Only 1 case of this late-onset disorder has yet been reported as a pitfall of the transsphenoidal route. Symptoms include recurrent headache and visual complications. Diagnosis was delayed because of misinterpretation of the magnetic resonance imaging findings, which actually showed the development of a sphenoid mucocele long before clinical symptoms occurred. These 3 cases suggest that attention should be focused not only on the sella turcica, but also on the sphenoid sinus, in analyzing the magnetic resonance imaging data. The treatment consists of endoscopic transnasal marsupialization, since the mucocele is lined by normal epithelium with an inflammatory reaction that will heal with drainage. At the time of surgery, prevention would require either endoscopic control of the mucosal remnants, in case of sinus exclusion, or leaving the sphenoid sinus air-filled under a sealed sella.
OBJECTIVE: To assess the sensitivity of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) in the diagnosis and the follow-up of cerebral venous thrombosis (CVT). To describe MRI and MRA features in CVT. MATERIAL AND METHODS: The clinical and neuroradiological studies of 20 patients with proven CVT were reviewed. All patients underwent computed tomography (CT), MRI (with MRA for 15 patients) and digital substraction angiography (DSA). Eleven patients had follow-up after treatment with MRI (nine with MRA). RESULTS: MRI and MRA together provided the diagnosis of CVT in all cases. The sensitivity of MRI alone was 90%. MRA showed abnormalities in all cases of CVT. Progressive sinus recanalization was demonstrated by follow-up with MRI and MRA at least 15 days after diagnosis and treatment. CONCLUSION: In most of cases, the combination of MRI and MRA is sufficient to allow diagnosis of CVT and obviates the need for invasive angiography. MR studies are also useful for the follow-up of CVT.
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