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M Genton

Publications and source records attributed to M Genton.

9 recordsLinked to original sources
PubMed1998

Assessment of the global two-stage method to EC50 determination.

Preclinical studies of a new drug supply sets of concentration-effect observations. For each experiment, EC50 is estimated through fitting of the Emax model. Naive pooling of these individual estimates, also called the Standard Two-Stage method (STS), is usually performed. A better combination is obtained by the Global Two-Stage method (GTS) which takes into account the variability of the nonlinear regression estimation errors. The performances of STS and GTS are compared on real and simulated data. The results show that GTS performs better than STS in terms of bias or RMSE, especially in case of poorly designed experiments. Degradation of the quality of STS results in simulations appears to be mainly due to some experiments that are usually rejected by experimenters. Such rejections are avoided when using GTS, which hence is particularly suitable for systematic treatment of this kind of data.

Chemistry, Pharmaceutical↗
PubMed1988

Multiple sclerosis: a serial study using MRI in relapsing patients.

Prospective monthly magnetic resonance imaging (MRI) studies were done over 6 months in seven relapsing MS patients. MRI and neurologic evaluations were compared for sensitivity in detecting disease activity. Four patients were clinically stable throughout the study. Three patients had five clinical relapses, two localized to the spinal cord and three to the brainstem. Eighteen new and ten enlarging MRI lesions were seen in five patients. Most lesions were less than 10 mm in diameter. All were clinically silent. Two patients developed major enlarging MRI lesions (seen in three slices) which increased in size over 2 months and then gradually became smaller over 2 months, leaving behind small residual areas of abnormality. There were 36 follow-up scans, 17 of which (47%) showed evidence for increasing activity. Thirteen (36%) of the scans had new lesions, most of them being small. This study shows that MRI evidence for disease activity in MS is much more frequent than is clinical evidence.

Adult↗
PubMed1988

Gadolinium-DTPA-enhanced MR imaging of spinal neoplasms: preliminary investigation and comparison with unenhanced spin-echo and STIR sequences.

Unenhanced T1- and T2-weighted spin-echo, short inversion time inversion recovery (STIR), and gadolinium-DTPA (Gd-DTPA)-enhanced spin-echo and STIR imaging techniques were used in 20 patients as part of a multicenter study to assess the safety and efficacy of Gd-DTPA in spinal imaging. Five patients had normal MR scans. Of those with lesions, both Gd-DTPA-enhanced T1-weighted spin-echo and unenhanced STIR scans improved detection and evaluation of spinal tumors over conventional spin-echo methods, particularly T2-weighted spin echo, by providing higher tissue contrast in shorter imaging times. The Gd-DTPA-enhanced T1-weighted spin-echo scans were most helpful in evaluating intradural tumors, whereas STIR sequences were most effective for extradural tumors and bone metastases. In most cases, Gd-DTPA-enhanced T1-weighted spin-echo scans best delineated tumor margins, and the enhancement was helpful in suggesting a cellular or active nature of the lesions. In some cases, the enhancement resulted in a more homogeneous and thus less abnormal-appearing marrow in vertebrae involved by tumor; therefore, a precontrast T1-weighted spin-echo scan is necessary in all patients who are to be studied with Gd-DTPA. A combined approach that uses T1-weighted spin-echo, Gd-DTPA-enhanced T1-weighted spin-echo, and STIR images currently appears optimal for MR imaging of spinal neoplasms. T2-weighted spin-echo images add information only in occasional cases.

Bone Marrow↗
PubMed1982

Further support for the central origin of the gastric antisecretory properties of clonidine in conscious rats.

The effects of clonidine (CL) on interdigestive gastric acid secretion were studied in chronic gastric fistula rats and compared with those of St 91, a CL-like drug which does not cross the blood-brain barrier. CL induced a dose-dependent inhibition of gastric acid output when administered s.c. (ED50 13.5 micrograms X kg-1), in the lateral ventricle of the brain (ED50 5.80 micrograms X kg-1) or in the cisterna magna (ED50 0.49 micrograms X kg-1). St 91 and several alpha-adrenergic antagonists administered subcutaneously also inhibited gastric acid secretion dose dependently. Decreasing activities were prazosin greater than St 91 greater than phentolamine greater than yohimbine greater than piperoxan; phenoxybenzamine was a poor inhibitor. The anti-secretory properties of CL on basal secretion were antagonized by yohimbine and piperoxan. Other drugs either did not antagonize (phentolamine) or potentiated (phenoxybenzamine, prazosin) the CL effect, while yohimbine and phenoxybenzamine potentiated the response to St. 91. CL had no activity on methacholine while it drastically inhibited 2-DG-, histamine- and pentagastrin-stimulated gastric secretion. The inhibitory activity of CL on histamine stimulation was significantly decreased by yohimbine but not by phentolamine. These results confirm that the CL inhibition of the gastric acid secretion in unanesthetized rats is mediated at least partly through the stimulation of alpha 2-adrenergic receptors. Most of the data favour a major role of the CNS in the antisecretory activity of CL and suggest the possibility that most of the receptors involved are located in the medulla oblongata.

Adrenergic alpha-Antagonists↗
PubMed1982

Intestinal motility responses to insulin and glucagon in streptozotocin diabetic rats.

Myoelectrical and mechanical activities were chronically recorded by use of nichrome electrodes and miniaturized strain-gage transducers sutured on the serosa of the antrum, the duodenum, and the jejunum. In a first experiment (n = 6 rats) the early (0-6 h) and late (greater than 4 days) effects of streptozotocin (65 mg/kg i.v.) was recorded. In addition, the effect of insulin (1-5 IU/kg) and glucagon (6-200 micrograms/kg) administered intravenously were studied separately each in groups of seven normal and streptozotocin-induced diabetic-fed and fasted rats. The results indicated that within the 30 min following streptozotocin administration there was a significant stimulation of the duodenal and jejunal motility lasting 46 +/- 8 min. When diabetes was established as shown by the basal blood glucose level obtained in those rats (2.30 +/- 0.84 g/L), a progressive decrease of the frequency of the migrating myoelectric complex was observed along with a disorganization of the regular spiking activity phases without disturbing the basal electrical rhythm. Comparing with the basal level, a significant increase in the gastrointestinal motility indexes (MI) appeared both in fasted (p less than 0.01) and fed (p less than 0.05) normal animals, 13.1 +/- 1.6 min after an i.v. injection of 1 IU/kg insulin. Motor effects of glucagon were related to the dose. When used at 25 microgram/kg a disorganization of the spiking activity was observed with a stimulation of the contractile activity in the jejunum. At higher dosages, i.e., 100 micrograms/kg, it induced an immediate and significant decrease of motility at any level tested and lasting up to 20 +/- 7 min. The motility responses to both hormones were lower in diabetic than in normal rats.

Animals↗
PubMed1981

Continuous electrical and mechanical activity recording in the gut of the conscious rat.

The chronically-prepared gut is a very useful model for the determination of the motor profile changes due to drugs in both fed and unfed animals. Rats fitted with strain gauge transducers and implanted electrodes showed a good relationship between motility indices of spiking activity and mechanical activity. In both fed and fasted rats records of contractions of the antrum gave a more accurate representation, as tonic changes in antral activity can be seen. On the other hand, the electrical spiking activity of the small intestine allows more accurate recording of pharmacological responses than recording of the mechanogram. These variations as well as the changes in the duration of quiescence may be of importance in the quantitative assessment of the gastrointestinal motor profile.

Animals↗