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Biomedical subjects

P Benoit

Publications and source records attributed to P Benoit.

At least 37 records · Page 2Linked to original sources

[Additional contribution of high amplification electrocardiography in the follow-up of children with muscular dystrophy].

Fifteen children and adolescents with muscular dystrophy underwent investigation by Doppler echocardiography and high amplification electrocardiography to evaluate the quality of left ventricular function. High amplification ECG showed minor intra-atrial conduction defects in 3 cases and abnormal late micro potentials without arrhythmogenic late potentials in 3 other cases. Significant abnormalities were observed in 40% of children examined. Doppler echocardiography showed relative conservation of systolic left ventricular function but a decrease in indices of contractility was observed in 46% of cases, especially in patients with Duchenne muscular dystrophy. Abnormalities of left ventricular distensibility were observed earlier and were more common (53% of cases). A significant decrease in cardiac output was found in 50% of patients, especially among the older and more severely affected children irrespective of the type of muscular dystrophy. These two investigations provide complementary information for the evaluation of left ventricular function of children with muscular dystrophy and they are proposed routinely for the follow-up of these patients.

Adolescent

Extent of multiple innervation of cerebellar Purkinje cells by climbing fibers in adult X-irradiated rats. Comparison of different schedules of irradiation during the first postnatal week.

The multiple innervation of cerebellar Purkinje cells (PCs) by climbing fibers (CFs) that is transient in normal developing rats can be experimentally maintained in cerebella which have been degranulated by repetitive postnatal X-irradiation restricted to the first postnatal week. Since the involution of redundant CFs occurs essentially between postnatal days 5 and 10, and given that postirradiation effects last 2-3 days, the question arose to know whether it is possible to further delimit a 'critical period' of irradiation within the first week. An estimate of the extent of multiple innervation of PCs by CFs was made in adult rats that had been irradiated according to 5 different schedules: in two groups, rats received X-rays applied repetitively during the first postnatal week (PN0-7 groups); in the 3 other groups, X-rays were delivered either during the first part of the week (early group PN1-3) or during the last part of the week (late groups PN4-7). In addition, two daily doses were tested (150 and 200 r). The CF pathway was electrically stimulated in anesthetized rats at the level of the inferior olive or in the cerebellar white matter. Intracellular recordings of spontaneous and evoked CF responses in PCs allowed to estimate the number of afferent CFs and to calculate the mean value (m) per PC for each group. The majority of recorded cells was located in lobules VII and VIII and similar results were obtained in these two lobules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers: a role for hematopoietic growth factor release by tumor cells?

One hundred six primary breast cancer samples were analysed for c-erbB2, int-2, and c-myc gene amplification. Surgically confirmed nodal involvement was observed in 42%. Level of gene amplification was studied by Southern and/or slot blot techniques. Amplified c-erbB2 gene sequences were present in 21.5% of all samples. Int-2 was amplified in 13.1% and c-myc was amplified in 10.3%. In a non-parametric test (Kruskal-Wallis) a strong negative association was found between high levels of c-erbB2 amplification and absence of estrogen receptor (ER) (P = .0009) or progesterone receptor (PR) (P = .011) expression. No correlations were found between all or high levels of amplification of each oncogene separately or combined with T, N, grade, multifocality of tumor, or associated carcinoma in situ. There was a trend approaching statistical significance for patients with c-erbB2 amplifications to have positive lymph nodes at surgery (P = 0.09). A somewhat surprising finding however was a very strong association between oncogene amplification and dense lymphocyte infiltration of the tumor (P = .05). This correlation is even stronger when only high levels of amplification are considered, either for each oncogene separately (P = .0048) or in combination (P = .0007). We propose that malignant cell cytokine production may help explain this observation.

Breast Neoplasms

Manipulation of the immune response by monoclonal antibodies in auto-immune pathology.

Murine monoclonal antibodies have proven to be invaluable tools in medical research and diagnosis. However, their use as therapeutic agents remains limited since these proteins can act as foreign antigens in the human host. An immune response subsequent to administration of monoclonal antibodies may result in unpredictable in vivo distribution and insufficient interaction with cellular or molecular targets of the immune system. Also, the patient may produce anti-antibodies that can neutralize the effects of the therapeutically administered monoclonal antibodies. Treatment of auto-immune disease is an important potential therapeutic application of monoclonal antibodies, provided that these difficulties can be overcome.

Animals

[Progression from hypertrophic obstructive cardiomyopathy to dilated cardiomyopathy. Apropos of 4 cases].

Four cases of hypertrophic obstructive cardiomyopathy diagnosed on clinical, phonomechanographic, echocardiographic and haemodynamic criteria progressing to dilated cardiomyopathy are reported. This evolution was observed over a number of years (up to 20 years) and was accompanied by a clinical aggravation in all cases with 2 deaths and atrial fibrillation in 3 of the 4 cases. The signs of intraventricular obstruction [systolic murmur, bulge on the carotid pulse tracing, systolic anterior motion of the mitral valve (SAM) and intraventricular pressure gradient] disappeared as the left heart chambers dilated with a reduction in ventricular wall motion and parietal thinning but no change in myocardial mass.

Adult

Calcium rise in human platelets elicited by anti-CD9 and -CD41 murine monoclonal antibodies.

Three murine monoclonal antibodies (anti-CD9: ALB6, anti-CD41: VI-PL3 and PL2-49/GPIIb - final concentration: 7.5 micrograms/mL) are shown to elicit after a lag time aggregation of washed platelets and a calcium signal (as detected by light emitted by loaded aequorin), which is only partially inhibited by aspirin. By comparison the rise induced by thrombin is greater and almost instantaneous. In the presence of EGTA a calcium mobilization from internal stores can be detected with thrombin and with ALB6, but neither with PL2-49 nor with VI-PL3, whereas platelets still change their shape and release ATP. It is tempting to speculate that although all the antibodies induce a calcium change, they activate platelets by different pathways: calcium may be not primarily involved in the activation induced by the anti-CD41 antibodies.

Adenosine Triphosphate

Calcitonin gene-related peptide enhances the rate of desensitization of the nicotinic acetylcholine receptor in cultured mouse muscle cells.

Calcitonin gene-related peptide (CGRP) is a neuropeptide that coexists with acetylcholine in spinal cord motoneurons. The effects of CGRP on the functional properties of the nicotinic acetylcholine receptor (AcChoR) were examined by electrophysiological methods. Using the whole-cell patch-clamp technique and a mouse cell line derived from soleus muscle, we found that CGRP produces a progressive and reversible enhancement of the rapid-decay phase of AcChoR desensitization. Single-channel data further show that CGRP decreases acetylcholine-activated channel opening frequency. This decrease occurs when CGRP and acetylcholine are applied on different cell-surface areas and thus is likely mediated by a second-messenger system. CGRP is also shown to increase cAMP accumulation in this cell line. The effects of CGRP on macroscopic acetylcholine-activated currents are mimicked by external application of forskolin (10 microM) or by internal perfusion of the cell with cAMP (1 microM). In both these cases, further application of CGRP produces no additional enhancement of AcChoR desensitization. These results suggest that, on mouse muscle cells, CGRP regulates AcChoR desensitization by a mechanism that involves, at least in part, cAMP-dependent phosphorylation of the AcChoR.

Animals

[Hemodynamic effects on intravenous propafenone in hypertrophic myocardiopathy].

None of the medical treatments of hypertrophic cardiomyopathy is perfect. In the present study conducted on 11 patients with hypertrophic cardiomyopathy in whom the usual treatments were either ineffective or badly tolerated, the haemodynamic effects of propafenone administered intravenously were investigated. The drug was injected centrally in doses of 2 mg/kg over 10 minutes, then by continuous intravenous infusion of 1.5 mg/min during 30 minutes. Various parameters were recorded before and after propafenone treatment by right and left cardiac catheterization. This anti-arrhythmic drug, which has beta-blocking and amiodarone-like properties, reduced left intraventricular obstruction but had no beneficial effect on diastolic function. The baseline and induced left intraventricular gradients were reduced from 30.4 to 17.7 mmHg and from 74 to 43 mmHg respectively. Diastolic function values showed a fall in dp/dt min from 1470 to 1307 mm/sec and an increase in T value from 0.066 to 0.084. The use of propafenone in hypertrophic cardiomyopathy must be accurately determined by long-term oral studies.

Adolescent

[Borrelian meningoencephalomyelitis. A case].

A 22-year old man had spastic paraparesis and cerebellar syndrome of 5 months duration. CSF showed lymphocytosis, elevated protein content, hypoglycorachia, hypochlorurachia and oligoclonal banding. CT scan and MRI were normal. Extensive laboratory procedures disclosed no bacterial, viral, fungic, parasitic or inflammatory disease. Anti-Borrelia burgdorferi antibodies were present in blood (1/4000) and in CSF (1/1024). With antibiotics (penicillin G 20 millions units per day for 10 days, followed by latamoxef 1.5 g per day for 3 months) and prednisone (50 mg per day for 2 months), the cerebellar signs disappeared, the paraparesis improved and the CSF abnormalities disappeared; blood and CSF anti-Borrelia antibody levels decreased. This case is an example of a severe form of CNS impairment by Borrelia burgdorferi. In Europe, most reports show progressive para- or tetraparesis with, sometimes, intellectual, cerebellar or cranial nerve impairment. In some cases, the signs are less diffuse or more acute. Lymphocytic meningitis is present with hyperalbuminorachia and oligoclonal banding; hypoglycorachia is mentioned in only one other report. Diagnosis is made by high blood and CSF antibody titers and demonstration of local synthesis. As in syphilis, borrelian meningoencephalomyelitis could be the third stage of the disease. Its treatment, often disappointing, consists of antibiotics (penicillin G or latamoxef) and in some cases corticosteroids.

Adult

Mechanisms of the mAb ALB6(CD9) induced human platelet activation: comparison with thrombin.

A CD9 monoclonal antibody described to aggregate human platelets was studied on different platelet functions in order to determine its mechanism of action. After a lag phase of 35 sec the mAb ALB6 induced a transient decrease in 32P-polyphosphoinositides, synthesis of 32P-phosphatidate (PA), phosphorylation of myosin light chain (P20) and of 43 KDa protein (P43) and the release reaction. Final biological and metabolic effects of ALB6 thus appear similar to that of thrombin but three differences bring additional information: (i) the lag phase, (ii) the kinetic of ALB6-induced release is identical for all granules whereas the release of dense granules is faster when induced by thrombin. (iii) no external Ca++ is required for ALB6 induced-activation.

Antibodies, Monoclonal

Renal metastases from neuroblastoma. Report of two cases.

Neuroblastoma is one of the pediatric cancers that has the most unpredictable evolution. It can metastasize to almost any organ, but intrarenal metastases have never been reported. We report 2 such cases: the first patient had a left adrenal neuroblastoma completely resected 10 months before routine follow up ultrasound and CT scan demonstrated 3 right intrarenal metastases. The second patient was being investigated for a left abdominal mass when one left intrarenal metastasis was found during the same CT scan. An intrarenal mass found during investigation for staging or follow up of neuroblastoma should then be considered as a metastase until proven otherwise.

Adrenal Gland Neoplasms

Evidence for a multiple innervation of cerebellar Purkinje cells by climbing fibers in adult ferrets infected at birth by a mink enteritis virus.

Newborn ferrets were inoculated with Mink Enteritis virus (parvovirus). They developed a cerebellar hypoplasia and presented severe ataxia. Electrophysiological study by intracellular recordings in the cerebellar cortex demonstrates that in these ferrets, like in other mammals, Purkinje cells deprived from granule cell input during development remain multiply innervated by climbing fibers in the adult.

Animals

Lateral gaze disturbance in a case of Wallenberg's syndrome.

A 63-year-old Caucasian man was admitted for Wallenberg's syndrome following a left vertebral artery thrombosis. In addition to the classical symptoms, an axial lateropulsion to the left and ocular motor disorders (vertical diplopia, tonic deviation of the gaze to the left, skew deviation and horizonto-rotatory nystagmus) were present. These clinical signs are unusual, but in common Wallenberg's syndrome, neurophysiological tests often reveal slight abnormalities of oculomotor function: impairment of jerks, skew deviation, lateral deviation of the gaze in darkness. Interruption of cerebellar pathways is thought to be the cause of these symptoms. Their existence does not seem to change the outcome of these cases.

Eye Movements

Chondroma of the cervical spine. Case report.

The authors report a case of cervical chondroma presenting with a syndrome of spinal cord compression in a 76-year-old woman. Total surgical removal of the lesion was followed by partial neurological recovery. Chondromas of the vertebral column are rarely reported in the literature.

Aged