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Biomedical subjects

J C Baron

Publications and source records attributed to J C Baron.

At least 127 records · Page 7Linked to original sources

Neuroimaging procedures in acute ischemic stroke.

Recently, neuroimaging procedures have been applied extensively to the acute-stage assessment of ischemic brain damage. Positron emission tomography studies of brain perfusion and oxygen metabolism performed within 18 hours of stroke onset both depict the amount of already irreversibly damaged tissue and accurately predict the subsequent neurologic course in a sizeable fraction of patients. The prognosis is poor in those patients with extensive irreversible damage and good when early spontaneous reperfusion has occurred before cortical damage has been established. The remaining patients, in whom ischemia is still ongoing and the neurological course is unpredictable, may constitute a subgroup more amenable to trials of therapy. New developments in diffusion-weighted magnetic resonance imaging suggest this noninvasive tool, like positron emission tomography, may be sensitive to failure of energy metabolism very soon after ischemia begins. Studies in rats suggest it may be possible to differentiate still salvageable tissue from irreversibly compromised tissue with this technique. Ultra-fast diffusion-weighted magnetic resonance imaging is feasible in humans and preliminary observations suggest the technique is as sensitive in humans as it is in rats. The usefulness in acute stroke management of other magnetic resonance techniques still in development, such as blood volume and perfusion imaging, deoxyhemoglobin-sensitive sequences, and 1H or 31P spectroscopy, remains to be assessed.

Brain↗

In vivo mapping of brain benzodiazepine receptor changes by positron emission tomography after focal ischemia in the anesthetized baboon.

BACKGROUND AND PURPOSE: Recent reports have shown an increase in specific binding (in vitro) of [3H]PK 11195 to peripheral-type benzodiazepine receptors in both experimental animals and humans, reflecting a glial/macrophagic reaction within and around focal ischemic insults. We have evaluated by positron emission tomography the time course of changes in brain uptake in vivo of 11C-labeled PK 11195 and flumazenil (an antagonist of central benzodiazepine receptors) as indirect and direct markers of neuronal loss, respectively, after focal cerebral ischemia. METHODS: Ten anesthetized baboons were submitted to sequential positron emission tomography studies between day 1 and day 91 after unilateral middle cerebral artery occlusion. The studies consisted of successive assessments, in the same positron emission tomography session, of [11C]PK 11195, [11C]flumazenil, cerebral blood flow, and oxygen consumption; late computed tomographic scans were obtained to map the approximate contours of infarction and to define a concentric peri-infarct area. RESULTS: We found a significant time-dependent increase in [11C]PK 11195 uptake in the peri-infarcted area, maximum at 20 to 40 days after occlusion. In contrast, there was a time- and perfusion-independent significant decrease in [11C]flumazenil uptake in the infarcted area, stable from day 2 onward, and already present in one baboon at day 1. Challenge studies with saturating doses of cold ligands confirmed that these changes represented alterations in specific binding. [11C]Flumazenil uptake was not affected in hypometabolic (but apparently noninfarcted, ie, deafferented) cortical areas. CONCLUSIONS: The delayed and apparently transient increases in [11C]PK 11195 specific uptake in vivo presumably represent glial/macrophage reaction; the marked depression in [11C]flumazenil specific binding, which appears selective for synaptic damage, is both precocious and sustained and thus may be better suited for the early assessment of ischemic damage in humans.

Animals↗

[Cerebral and cardiovascular aging and brain energy metabolism. Studies with positron-emission tomography in man].

Positron emission tomography (PET) is the only method that measures concomitantly in the same cerebral region the main haemodynamic (blood flow, blood volume) and metabolic (oxygen and glucose consumption) parameters, thereby providing essential data concerning the supply of substrates by circulation and their principally neuronal/synaptic use by the cells. In "healthy" (i.e. normal) ageing, there is a progressive decrease of oxygen and glucose consumption--with subsequent reduction of cerebral blood flow (CBF)--which predominates in the neocortex and suggests a dysfunction of neuronal circuits perhaps responsible for some age-related changes in cognitive functions. The metabolic depression in the neocortex seems to be accentuated during the more "common" ageing which may include cerebrovascular risk factors, lesions of the white matter in varying numbers and/or degradation of cognitive functions. Strategically located brain lesions of vascular origin (e.g. damaging of the thalamic nuclei), may produce a thalamo-cortical disconnection which induces a diffuse cortical hypometabolism associated with severe cognitive disorders. In degenerative dementias (particularly Alzheimer's disease), which include cortical and subcortical neuronal lesions (e.g. those involving the cholinergic system), there is a hypometabolism preferentially affecting the associative cortex. The cumulative effects on cortical functioning of multiple vascular lesions, superimposed on degenerative neuron loss, might account for age-related cognitive disorders in "normal" ageing as well as in the so-called "vascular" or "mixed" dementias.

Adult↗

Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.

Adult↗

[Risk factors for tumors of the bladder. Epidemiological study of 701 patients in Ile-de-France].

The authors present the results of an investigation conducted, under the aegis of the PETRI association, on 701 patients living in the Paris region who, over a 1-year period, had asked the medical advisers of the Social Security Sickness Benefits department to dispense them from paying their portion of the cost of treatment on the ground that they had cancer of the bladder*. The purposes of the investigation were to obtain accurate data concerning the role played by tobacco and alcohol abuse in bladder cancer and to look for possible occupational exposures. The smoking and drinking habits of 636 patients could be analyzed: 89 percent of the men were, or had been, smokers with an average consumption of 33 packs per annum, and with a frequent overconsumption of alcoholic drinks. The professional cursus of 665 patients (31 percent active, 64 percent retired) could be established. The study confirmed that tobacco smoking and alcohol abuse, as well as certain occupational factors, play a role in the development of bladder cancer. Some professional sectors, such as the plastic industry or the hide and leather work, were better represented among these patients than would have been expected from their distribution in the active population. Surveillance of the population exposed by industrial doctors, and follow-up of people who have retired from some sectors of activity are as essential as anti-smoking campaigns.

Adult↗

Regional cerebral oxygen consumption, blood flow, and blood volume in healthy human aging.

Using high-resolution positron emission tomography and the oxygen 15 continuous inhalation method, we examined the changes in cerebral metabolic rate of oxygen, blood flow, blood volume, and oxygen extraction fraction as a function of age in 25 optimally healthy, unmedicated volunteers who ranged in age from 20 to 68 years. Subjects were strictly selected for absence of cerebrovascular risk factors, dementia, or mental disorders; they had neither biological nor clinical abnormalities, and no focal anomaly on computed tomographic scan. Regions of interest were determined according to the anatomical structures defined on corresponding computed tomographic scan cuts obtained using a stereotaxic head-positioning method. This same method was also used for positron emission tomographic imaging. There was no significant effect of aging on PaCO2 values, hematocrit, arterial blood pressure, cholesterol and triglyceride levels, and blood glucose levels. In most cerebral cortex gyri, the cerebral metabolic rate of oxygen significantly decreased with age according to a linear pattern, with the same magnitude (about -6% per decade) in all four lobes and on both sides. This effect of age on cortical cerebral metabolic rate of oxygen persisted when the possible influence of cortical atrophy, gender, and head size were partialled out. In contrast, the white matter, deep gray nuclei, thalamus, and cerebellum were not significantly affected. The cerebral blood volume declined with a similar pattern to cerebral metabolic rate of oxygen, while changes in cerebral blood flow were less significant, presumably because of larger variance of data across subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ureterorectal diversion with rectal augmentation. Morphological and manometric study in the dog.

Uretersigmoidostomy in the adult has progressively been abandoned because of its high complication rate (both metabolic and functional). We have studied the feasibility of a new model of ureterorectal diversion in 12 Beagle dogs, with the aim of increasing rectal capacity and decreasing rectal pressure. A segment of the ileum was isolated and opened along its antimesenteric border to obtain a patch into which the right ureter was implanted, the left ureter being left intact to allow comparison of the kidneys postoperatively. The patch was then sutured to the edges of a large anterior rectotomy. Modifications of rectal physiology were studied by recording the rectal pressure after distension by a latex balloon both preoperatively and 3 months postoperatively, so that it was possible to evaluate the elasticity of the rectal wall. Radiographic studies and examination of autopsy specimens after 3 months yielded the impression of a reservoir added to the rectal space. Intrarectal pressure was significantly decreased (50% of the preoperative value) for a given distension volume following rectal augmentation (P less than 0.01). The elasticity of the rectal wall was not modified but the capacity of the reservoir was increased. The ureteroileal implantation was patent in two of the five evaluable dogs out of seven implantations performed. In these cases, signs of pyelonephritis were found in the right kidneys. In the remaining cases the implantation became obstructed for reasons mainly related to canine anatomy and experimental conditions. These technical difficulties in the dog make it impossible to assess the quality of this reimplantation technique in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthesis and regional rat brain distribution of [11C]MDL 72222: a 5HT3 receptor antagonist.

MDL 72222, an antagonist of 5HT3 receptors, was labeled with a specific radioactivity of 340-400 mCi/mumol by alkylation of the nor-precursor with [11C]CH3I. The yield of the synthesis, starting from [11C]methyliodide to the purified product and corrected for decay, was good approximately 70-75%. After i.v. injection, [11C]MDL 72222 diffuses readily in the central nervous system but is not detected as metabolites in brain and blood, during 1 h study carried out in rats. The time course and distribution of [11C]MDL 72222 was assessed in various organs (liver, lung, kidney, heart, whole brain) and in blood; the organ uptake was rapid and large; the highest accumulation was found in the lung. The regional brain distribution shows initial uptake and subsequent retention of tracer in favor of the cerebral cortex. The level of brain radioactivity was not reduced by pretreatment with a 1000-fold excess of unlabeled MDL 72222. These results suggest that [11]MDL 72222 is of limited interest for 5HT3 receptor binding studies in brain in vivo, presumably mainly because of large non-specific binding.

Animals↗

Brain energy metabolism in bilateral paramedian thalamic infarcts. A positron emission tomography study.

Positron emission tomography (PET) studies of the cerebral metabolic rate of oxygen (CMRO2) were performed in seven consecutive patients with bilateral paramedian thalamic infarcts (BPTI), selected on neuroradiological and clinical criteria. The latter consisted of sudden onset of coma or confusion followed by a persistent amnesia of varying severity, with or without language impairment and frontal lobe signs. There was a highly significant decrease of CMRO2 for the whole cortex as well as for all the regions analysed: medial-frontal, latero-frontal, temporal, sensorimotor and posterior associative cortex. The mean regional metabolic ratios (region/whole cortex CMRO2) were not significantly different from controls, indicating an essentially uniform effect in the cortex, except the sensorimotor ratio which was significantly increased. Diffuse cortical hypometabolism most likely reflects thalamo-cortical deafferentation secondary to damage to the 'non-specific' thalamic nuclei, while sparing of the latero-ventral thalamus presumably explains the relative preservation of the sensorimotor cortex metabolism. Although no clear-cut individual relationship was found between magnitude of cortical hypometabolism and the severity and pattern of neuropsychological impairment, the data suggest that the former underlies and/or reflects the latter. Further studies with higher resolution PET devices might shed more light on the relationships between distinct cognitive patterns and specific topography of cortical hypometabolism in BPTI patients.

Adult↗

Cortical metabolism in posterolateral thalamic stroke: PET study.

In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the 18F-fluorodeoxyglucose or the 15O-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the "non-specific" thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain.

Aged↗

Thalamocortical diaschisis: positron emission tomography in humans.

To investigate further the relations between cortical energy metabolism and neuropsychological impairment after unilateral thalamic lesion, 55 patients underwent positron emission tomography studies of either cortical oxygen consumption or glucose utilisation, including eight repeat studies, at times ranging from 4 days to 98 months after the onset of the lesion [stroke (n = 44) or stereotaxic VL-Vim thalamotomy performed for movement disorders (n = 11)]. Patients with thalamotomy were also studied preoperatively and the surgery induced a significant fall in cortical metabolism on both sides (more so ipsilaterally); post-operatively the magnitude of the ipsilateral cortex hypometabolism was positively correlated to the severity of global neuropsychological impairment; similar but less significant findings were obtained for the ipsilateral/contralateral cortical metabolic asymmetry. With respect to the whole patient sample, the cortical metabolic asymmetry was initially pronounced, with subsequent monoexponential recovery, in the cognitively impaired study group, but it was only mild and showed no meaningful trend for recovery in the cognitively unaffected study group; yet even soon (< 3 months) after thalamic lesion there was a noticeable overlap of individual asymmetry values among the two study groups. These results lend further support to the view that the neuropsychological impairment that frequently follows unilateral thalamic lesions is reflected in a depression of synaptic activity in both the overlying and the contralateral cerebral cortices. For individual patients, this study also illustrates the potentially misleading nature of the measured cortical metabolic asymmetry with respect to neuropsychological status, especially at late times after lesion, in part because side to side metabolic ratios do not reflect bilateral changes.

Adult↗

Advantage of systematic random ultrasound-guided biopsies, measurement of serum prostate-specific antigen level and determination of prostate volume in the early diagnosis of prostate cancer.

Two hundred and sixteen patients, presenting with a suspicious digital examination (stage T3 excluded) or a level of prostate-specific antigen (PSA) greater than or equal to 2.5 ng/ml, assessed by radioimmunoassay, underwent a transrectal ultrasound examination. Prostate volume was systematically calculated and correlated to PSA level. Biopsies were performed: (1) on suspicious peripheral hypoechoic areas; ultrasound-guided biopsies; (2) systematically on the 2 prostate lobes, whatever the result of transrectal ultrasound imaging:random systematic ultrasound-guided biopsies. In the 186 patients who had never undergone prostate surgery, ultrasound-guided biopsies showed 42 prostate cancers and random systematic ultrasound-guided biopsies showed 75; 14 of the 76 patients with normal digital rectal examination and transrectal ultrasound imaging had a prostate cancer. In the 30 patients who had previously undergone surgery for benign prostatic hypertrophy, random systematic ultrasound-guided biopsies showed 18 prostate cancers, 13% more than ultrasound-guided biopsies; 75% of patients with a serum PSA greater than 5 ng/ml had a prostate cancer. A very significant correlation was found between PSA level and prostatic volume (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

[Uretero-rectal diversion with rectal enlargement. Clinical results].

In some patients, after total cystectomy, the urethra cannot be used, preventing the creation of a replacement enterocystoplasty. In these cases, ureterocolonic or ureterorectal diversion constitutes an alternative to cutaneous diversion if its classical complications could be minimized. A ureterorectal diversion technique with rectal enlargement was performed in 6 patients: a segment of small intestine was raised, opened along its antimesenteric border, folded into a U-shape and sutured to the edges of a large rectotomy. The ureters were implanted into this patch of small intestine according to the mucosal tunnel technique. This technique was used in 4 men after total cystectomy with invasion of the prostatic urethra by their bladder tumour and in 2 women for incontinence due to sphincter destruction who refused cutaneous diversion. There was no mortality in this series. The postoperative complications consisted one prolonged but resolving fever in 2 cases. Out of 12 ureteric units, 4 cases of severe stenosis had to be reoperated and 3 cases of moderate stenosis were observed. All patients were continent during the day except for one women who complained of incontinence when changing positions. All patients were continent at night and had to get up to urinate twice. This preliminary experience shows that rectal enlargement as part of a ureterorectal diversion is followed by very satisfactory functional results. The creation of a colorectal invagination valve to prevent metabolic disturbances does not appear to be necessary. The ureteric implantation technique in the mucosal tunnel should be abandoned in favour of a procedure using an ileal tube interposed between the ureters and the rectum.

Female↗

[Extraperitoneal endoscopic lymph node dissection with insufflation in the staging of bladder and prostate cancer].

Endoscopic pelvic lymph node dissection was performed in 30 patients as part of the staging of prostate (19) or bladder (11) cancers. The technique, using a procedure of detachment of the retroperitoneal space with CO2 insufflation, is described. Complete bilateral dissection of the ilio-obturator lymph nodes was performed in 24 patients (80%) using conventional laparoscopic surgical equipment. Only a unilateral dissection could be performed in 6 other patients because of technical difficulties. The mean operating time was 72 minutes. The intraoperative and postoperative complications consisted of 2 venous injuries and one infection. A prospective study of systemic diffusion of CO2 demonstrated that the blood Co2 level increased significantly during the procedure, but could be controlled by adaptation of the ventilation. Postoperative monitoring of blood CO2 levels using a capnograph is recommended. 4 out of 30 patients (13%), 2 with prostate cancer and 2 with bladder cancer, had lymph node metastases. Amongst the other 26 patients, 12 were treated by radiotherapy (bladder cancer), 12 patients underwent perineal prostatectomy and 12 others underwent retropubic prostatectomy (5) or prostatocystectomy (7]). No intraoperative and postoperative morbidity related to endoscopic lymph node dissection was observed in the patients subsequently undergoing a radical operation. Endoscopic retroperitoneal lymph node dissection with CO2 insufflation is a rapid, safe and effective technique for staging of malignant pelvic tumours and constitutes an alternative to open surgery and to endoscopic transperitoneal surgery.

Endoscopy↗

Brain kinetics and specific binding of [11C]PK 11195 to omega 3 sites in baboons: positron emission tomography study.

We characterized, in vivo, using positron emission tomography in baboons, the kinetics and specific binding of i.v. injected [11C]PK 11195 to omega 3 sites in the brain. Following immediate access to brain tissue, the brain kinetics of [11C] K 11195 showed a slow elimination for the 60 min of study. Both coinjection and pulse-chase (at t = 8 min) with saturating amounts of cold PK 11195 immediately enhanced the availability of radiotracer to brain tissue, but also markedly increased the rate of washout. These effects presumably reflect displacement or inhibition of specifically bound [11C]PK 11195 to both peripheral and central omega 3 sites, respectively. These results indicate that [11C]PK 11195 has easy access and binds with moderate specificity to the normal primate brain in vivo.

Animals↗