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Biomedical subjects

P Girard

Publications and source records attributed to P Girard.

At least 19 recordsLinked to original sources

Visuotopic organization of corticocortical connections in the visual system of the cat.

It has recently been demonstrated that, in contrast with the retinogeniculocortical projection, the corticocortical connections in the cat present a high degree of convergence and divergence. This suggests that some corticocortical connections link nonvisuotopically corresponding regions. Using fine-grain electrophysiological mapping and anatomical tracing, we have set out to test this possibility by placing a small injection of retrograde tracer in area 17 and by comparing the extent of visual field encoded in the region of area 18 containing labeled cells and that represented in the uptake zone. The results demonstrate that the size of the labeled region on the surface of area 18 is independent of eccentricity and that, despite its anisotrophy, this region of labeling encodes a broadly circular region of visual field that is larger than that encoded in the uptake zone of the tracer in area 17. For example, in the representation of lower visual field, a virtual point in area 17 that encodes a visual field region 4 degrees in diameter receives afferents from a region of area 18 encoding a region 11 degrees wide. Examination of the density of labeled cells in the labeled zone in area 18 reveals that the highest density is observed in a region in visuotopic correspondence with the injection site. However, high labeling density is also occasionally found in patches that do not represent the same visual field region as the injection site. Many receptive fields of neurons recorded in the labeled zone in area 18 only partially overlap or fail to overlap the visual field region encoded by the injection site. The results also demonstrate that the extent of visual field encoded in the labeled zone in area 18 is the same as that represented in the region of intrinsic labeling in area 17. It is suggested that cortical afferents coming from several cortical areas and converging on a column of cells in area 17 cover the same extent of visual field and that this cortical network constitutes the structural basis for the modulatory regions of the receptive field as well as the synchronization of neurons in different cortical areas.

Animals

Relative efficacy of angiotensin converting enzyme inhibitors on mortality of patients with congestive heart failure: implications of randomized trials and role of the aetiology (ischaemic or non-ischaemic) of heart failure.

We examined the influence of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality in patients with heart failure of both ischaemic or non-ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors involving 1266 patients were selected. The follow-up period varied from 3 to 6 months. Four different ACE inhibitors were used in the 11 clinical trials. A total of 679 patients presented with an ischaemic heart failure and 587 with a non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed that mortality was significantly decreased in the ischaemic subgroup only (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non-ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although the two odds ratio are not significantly different, further randomized, placebo-controlled trials with ACE inhibitors are required in order to determine more precisely the benefit/risk ratio in patients with non-ischaemic heart failure.

Angiotensin-Converting Enzyme Inhibitors

Response selectivity of neurons in area MT of the macaque monkey during reversible inactivation of area V1.

1. Behavioral results in the monkey and clinical studies in human show remarkable residual visual capacities after a lesion of area V1. Earlier work by Rodman et al. demonstrated that visual activity can be recorded in the middle temporal area (MT) of the macaque monkey several weeks after a complete lesion of V1. These authors also tested the effect of a reversible block of area V1 on the visual responses of a small number of neurons in area MT and showed that most of these cells remain visually responsive. From the results of that study, however, it is difficult to assess the contribution of area 17 to the receptive-field selectivity of area MT neurons. To address this question, we have quantitatively measured the effects of a reversible inactivation of area 17 on the direction selectivity of MT neurons. 2. A circular part of the opercular region of area V1 was reversibly inactivated by cooling with a Peltier device. A microelectrode was positioned in the lower layers of V1 to control the total inactivation of that area. Eighty percent of the sites recorded in the retinotopically corresponding region of MT during inactivation of V1 were found to be visually responsive. The importance of the effect was assessed by calculating the blocking index (0 for no effect, 1 for complete inactivation). Approximately one-half of the quantitatively studied neurons gave a blocking index below 0.6, illustrating the strong residual responses recorded in many neurons. 3. Receptive-field properties were examined with multihistograms. It was found that, during inactivation of V1, the preferred direction changed for most neurons but remained close to the preferred direction or to its opposite in the control situation. During inactivation of V1, the average tuning curve of neurons became broader mostly because of strong reductions in the response to directions close to the preferred and nonpreferred. Very little change was observed in the responses for directions at 90 degrees to the optimal. These results are consistent with a model in which direction selectivity is present without an input from V1 but is reinforced by the spatial organization of this excitatory input. 4. Residual responses were found to be highly dependent on the state of anesthesia because they were completely abolished by the addition of 0.4-0.5% halothane to the ventilation gases. Finally, visual responses were recorded in area MT several hours after an acute lesion of area 17.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia

A new, compound-curved needle for vascular surgery.

A new, compound-curved needle has been designed and developed for vascular surgery from a unique stainless steel alloy, American Society for Testing Materials (ASTM) 45500. This needle has two different radii of curvature and a relatively straight body followed by a short, curved tapered point. Despite its geometry, it exhibits a similar sharpness, as well as resistance to bending and breakage, as did a curved needle with a single radius of curvature manufactured from the same alloy. The design of this new needle enabled the surgeon to pass it through the vessel wall with greater accuracy to a controlled depth and length of bite than the curved cutting edge needle with a single radius of curvature.

Biomechanical Phenomena

Anti Xa activity and prothrombinase inhibition in patients treated with two different doses of enoxaparin in gynecologic surgery.

A prospective open study was performed in a series of 547 patients undergoing gynecologic surgery. A dose of 20 mg of enoxaparin was administered to all patients 2 hours before surgery. Then patients at high risk of thrombosis (mostly oncologic surgery) received 40 mg of enoxaparin daily whereas those at moderate risk received 20 mg of enoxaparin daily. The principal aim of this prospective open study was to monitor amidolytic anti Xa activity and to study the inhibition of intrinsic prothrombinase using prothrombin consumption measurement as a simple and global test. A second aim was to investigate efficacy and tolerance of these regimens. Treatment tolerance was satisfactory with both regimens since the total incidence of bleeding was 1.8%. A single patient developed a clinically significant thrombosis during hospital stay. The results confirm and extend previous reports regarding a dose effect relationship between the dose of Enoxaparin and plasma Anti Xa activity 3 hours after s.c. injection. A significant relationship was found between Anti Xa activity and patients body weight. Interestingly a dose dependent inhibition of intrinsic prothrombinase was observed when using a one stage prothrombin consumption assay in whole blood. This test in whole blood can be considered as closer to physiological conditions than assays performed in citrated platelet rich or platelet poor plasma samples. The mechanism of intrinsic prothrombinase inhibition during prophylactic treatment with enoxaparin requires further investigation.

Adult

Visual activity in macaque area V4 depends on area 17 input.

It is known that some direct projections from the lateral geniculate nucleus terminate in area V4 of the macaque monkey. Retinal information can also bypass area 17 and reach V4 through relays in the superior colliculus and pulvinar. This raises the question whether area V4 is visually responsive in the absence of input from area 17. We tested this possibility by recording in area V4 while inactivating a region of area 17 by cooling. This led to a complete abolition of the visual responses of practically all the neurons whose receptive fields were included in the visual field region coded by the inactivated zone in area 17. In contrast, neurons whose receptive fields were outside this region remained visually responsive.

Animals

Visual activity in areas V3a and V3 during reversible inactivation of area V1 in the macaque monkey.

1. Behavioral studies in the monkey and clinical studies in humans show that some visuomotor functions are spared in case of a V1 lesion. This residual vision appears to be subserved at least partially by visual activity in extrastriate cortex. Earlier studies have demonstrated that neurons in area V2 lose their visual responses when V1 is reversibly inactivated. On the other hand, Rodman and collaborators have recently shown that neurons in the middle temporal area (area MT) remain visually responsive when V1 is lesioned or inactivated. The purpose of the present study was to determine whether area MT is unique among extrastriate cortical areas in containing visually responsive neurons in the absence of input from area 17. 2. A circular part of the opercular region of area V1 was reversibly inactivated by cooling with a Peltier device. In that condition, 149 sites were recorded in the retinotopically corresponding regions of areas V3 and V3a. 3. About 30% of sites in area V3a still responded to visual stimulation when V1 was inactivated. On the contrary, nearly all sites in area V3 ceased to fire to visual stimulation. Receptive-field properties were assessed with qualitative measures; for most single cells or multiunit sites that responded during V1 inactivation, these properties did not change during cooling. 4. These results suggest that area V3a could take part in spared visuomotor abilities in case of a lesion of V1. Areas V3a and MT are both part of the occipitoparietal pathway, which suggests that the residual vision observed after a lesion of area 17 may depend mostly on this pathway.

Animals

Pseudophakic retinal detachment.

We reviewed 165 cases of non-referred pseudophakic retinal detachment. Fifty-three eyes (32%) had sustained significant complications due to cataract surgery prior to retinal detachment; 45 eyes (27%) presented with grade B, C or D proliferative vitreoretinopathy. The overall reattachment rate was 84%. This was significantly higher in the posterior chamber lens group than in the iris-fixated lens or anterior chamber lens groups (93 vs. 69 and 81%). Our data show that uneventful extracapsular cataract extraction plus posterior chamber lens implantation offers the best chance of successful detachment surgery.

Adult

Expression of ras oncogene leads to down-regulation of protein kinase C.

The effect of mutated c-Ha-ras expression on Ca2+ and phospholipid-dependent protein kinase C (PKC) activity during the process of transformation was analysed using an inducible metallothionein-ras hybrid oncogene system. A close correlation was found between the timing of ras expression and the loss of PKC enzymatic activity measured in a cell-free system. Examination of the subcellular distribution of the enzyme in inducible and constitutive ras-transformants revealed that expression of ras was associated with an apparent translocation of PKC to the plasma membrane concomitant with down-regulation of PKC enzymatic activity in particulate as well as cytosolic fractions. Quantitation of PKC protein utilizing a PKC-specific antiserum showed that ras expression was associated with a decrease in the total amount of PKC protein present in the cell. We conclude that transformation by c-Ha-ras is accompanied by down-regulation of PKC activity and that the basis of this effect may, to a large extent, lie in the down-regulation of the amount of PKC protein.

Animals

Which experimental design for phase I clinical trials? Proposal for an investigational approach.

The choice of a protocol for the first administration to man of a new drug remains an unresolved problem for the researcher. There are few studies concerning dose-ranging experiments in phase I to determine the threshold and plateau doses of a new drug in a population. A simulation approach may help in evaluating different protocols, by considering how they could be optimized, and by selecting the best protocol for a given case.

Drug Evaluation

The place of simultaneous pharmacokinetic pharmacodynamic modeling in new drug development: trends and perspectives.

The potential applications in drug development of pharmacokinetic-pharmacodynamic modeling are numerous: optimal medication regimen, design of galenic forms, identification of specific effects of metabolites and enantiomers. Nevertheless, this methodology is presently under-used, as appears from an analysis of the literature. We examine this point as well as progress in both non-invasive pharmacodynamic measurement and specific experimental design that could lead to a future extension of PK-PD in toxicology and phase I drug development.

Drug Evaluation

Left main-stem bronchial stenosis complicating bronchial artery embolization.

A 36-year-old patient was found to have severe left main-stem bronchial stenosis two years after bronchial artery embolization (BAE) for hemoptysis. Embolization-induced bronchial ischemia appeared to be the only potential cause for the observed lesions, and, to our knowledge, this constitutes the first report of late bronchial sequelae following BAE. Despite balloon-catheter dilatation of the stenosis, the severity of poststenotic lesions led to left pneumonectomy. The anatomic data further supported the hypothesis of a complication of BAE. Clinicians and radiologists should be aware of this potential complication of a widely used therapeutic procedure.

Adult

Effects of dydrogesterone on hydroelectrolytic metabolism: a randomized double-blind study.

To determine a possible influence on sodium balance or blood pressure of a normal treatment with dydrogesterone, a randomized cross-over double-blind study was performed on 22 healthy young women. Each woman had (in random order) 1 cycle of treatment with dydrogesterone (20 mg/day during the last 12 days of the menstrual cycle) and 1 with equivalent placebo. On days 15 and 27 of each cycle the following data were noted: weight, systolic (SBP) and diastolic (DBP) blood pressures (mean of 13 measurements during 1 hour), natriuresis, kaliuresis, plasma renin activity (PRA) and plasma aldosterone concentration (P ald). For each variable the difference between day 27 and day 15 was calculated. The comparison between progesterone and placebo influence was made on these differences. Neither for sodium balance nor for blood pressure were there any statistically significant differences between placebo and dydrogesterone. However, the confidence intervals of the difference were rather large. There is a need for a more extensive study to confirm the absence of influence of progesterone on sodium balance and blood pressure.

Adult

[Acute infectious pneumopathies in adults: methods of identifying the causative agent].

Many sampling methods have been proposed to make a bacteriological diagnosis of community-acquired pneumonia. The diagnostic accuracy of these methods depend upon technical constraints which are hardly obtainable in real world situations. In hospitals, close cooperation between clinicians and bacteriologists can help improve the reliability of these techniques, but in current practice the benefits of bacteriological identification often compete with the empirical therapeutic approach. This approach must remain within defined limits, since its uncontrolled widening can lead to major drawbacks. Whenever possible, bacteriological identification of the offending organism must be of concern.

Acute Disease