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Biomedical subjects

J C Baron

Publications and source records attributed to J C Baron.

At least 109 records · Page 6Linked to original sources
PubMed1995

Loss of heterozygosity at 7q31 is a frequent and early event in prostate cancer.

It is widely accepted that an accumulation of genetic alterations plays an important role in the genesis of human cancers, but little is known about prostate cancer in this respect. Recent studies have identified regions on chromosome arms 8p, 10q, 16q, and 18q that are frequently deleted in human prostate cancer. We have previously described a loss of heterozygosity (LOH) at the Met locus on chromosome band 7q31 in a study of 20 localized prostate tumors. To determine whether a region on the 7q arm is important in the initiation and/or progression of prostate cancer, prostate tissue from 13 patients with confined prostate tumors, 17 with local extracapsular extension, and 13 with metastatic forms were analyzed for LOH, using a DNA probe for RFLP (pMetH) and 8 CA microsatellite repeats (7 on 7q21-q33 and 1 on 7p). Twenty (47%) of the 43 cases studied showed LOH at one or more 7q loci. The most frequently deleted region was chromosome 7q31.1-7q31.2, whereas the centromeric locus on 7q21 was generally conserved. The percentage of LOH was normally distributed around the D7S480 locus. Moreover, the rate of LOH in the 7q31 region was lower in metastatic tumors than in localized tumors. These results strongly suggest the presence of a tumor suppressor gene on the chromosome band 7q31 with an important role in the early stages of prostate cancer.

Chromosomes, Human, Pair 7↗
PubMed1994

Oncogene amplifications in early-stage human prostate carcinomas.

Oncogene amplifications are frequently found in solid tumours and are often associated with more aggressively growing forms of human cancer. The proto-oncogenes c-myc, c-erbB2/neu and the 11q13 band are the most frequently amplified regions in adenocarcinomas of various origins. The present study was undertaken to define whether c-myc, int2/FGF3 (11q13 region) and c-erbB2/neu genes are involved in prostate tumorigenesis. Tumours and peripheral lymphocyte DNA from 21 localized early-stage prostatic carcinomas were analysed by Southern-blot electrophoresis for amplification of the c-myc and c-erbB2/neu genes and the 11q13 region (int2/FGF3). We detected no amplification of these 3 oncogenes in our panel.

Biomarkers, Tumor↗
PubMed1994

Genetic alterations in localized prostate cancer: identification of a common region of deletion on chromosome arm 18q.

Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell into a malignant cell by allowing it to escape from normal control of growth. In prostate tumorigenesis, the current model envisages specific mutations of the TP53 tumor suppressor gene and loss of loci, detected by loss of heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, gastric, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early-stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.

Alleles↗
PubMed1994

Marchiafava-Bignami disease with dementia: severe cerebral metabolic depression revealed by PET.

The Cerebral Metabolic Rate of Glucose (CMRGlu) was measured with positron emission tomography and 18F-FDG in a patient with Marchiafava-Bignami Disease (MBD)-related dementia. Despite MRI evidence of lesions essentially limited to the corpus callosum (CC), but consistent with the cognitive pattern of cortical dementia, the CMRGlu was markedly reduced in the frontal and temporo-parieto-occipital association cortices. Disruption of cortico-cortical networks crossing the CC presumably contributed to, but may not in and by itself explain, the severity of the clinical-metabolic findings in this patient. An additional role could be played by microscopic white matter lesions and/or neocortical neuronal loss, which have been occasionally observed in post-mortem studies of MBD patients.

Adult↗
PubMed1994

Immersion and perfusion staining with 2,3,5-triphenyltetrazolium chloride (TTC) compared to mitochondrial enzymes 6 hours after MCA-occlusion in primates.

2,3,5-triphenyltetrazolium chloride (TTC) is commonly applied in rodents and cats as a marker of infarcted tissue as early as 20 min after the onset of focal ischaemia. At this stage it is suggested that it reflects hypoperfusion rather than failure of respiratory chain. Immersion of brain slices in TTC solution is preferable in comparison to perfusion with TTC in order to ensure, that enough TTC enters the post-occlusion tissue. We compared immersion technique versus perfusion technique 6 h after permanent occlusion of the left middle cerebral artery in 18 baboons. In addition, we assessed the function of the respiratory chain enzymes of stained and unstained tissue in three baboons. The immersion technique revealed an absence of TTC staining limited to subcortical structures in two animals. In seven experiments TTC indicated involvement of almost the entire MCA territory. The extent of the ischaemic lesion indicated by the perfusion technique was very similar. Tissue samples from the presumed infarcted areas revealed normal mitochondrial function. We conclude that perfusion and immersion technique do not cause significant different ischaemic delineation 6 h after middle cerebral artery occlusion. TTC staining appears to be a reliable method of evaluating volume of infarction in primates. Furthermore, absence of TTC staining 6 h after stroke onset is caused by energy or oxygen depletion rather than by mitochondrial injury.

Animals↗
PubMed1994

Right frontal cortex hypometabolism in transient global amnesia. A PET study.

A 60-year-old lady with previous hypertension was studied with PET in the acute (early recovery) phase of an otherwise typical episode of transient global amnesia (TGA). Follow-up over > 1 year was uneventful, and delayed CT scans and MRI showed no brain damage. No medical cause was disclosed despite extensive work-up. The PET study revealed a matched reduction in cerebral blood flow and oxygen consumption over the entire lateral frontal cortex on the right side, with an associated, less significant reduction in ipsilateral thalamic and lentiform nucleus metabolism, but sparing the hippocampal area. These changes, which had resolved at a repeat PET study 3 months later, suggest right prefrontal metabolic depression, possibly secondary to thalamic dysfunction, as the underlying mechanism for TGA in this case, consistent with the emerging involvement of the prefrontal cortex in strategies or control of memory traces retrieval. Thus, in analogy with permanent amnesia, TGA may be a core syndrome with several possible foci of dysfunction along the neuronal networks that subserve explicit memory. In the future, combined PET neuropsychological assessment in the acute stage of TGA may prove useful in defining distinct neuropsychological-topographical subtypes of this intriguing clinical entity.

Amnesia↗
PubMed1994

Contralateral cerebellar hypometabolism: a predictor for stroke outcome?

Contralateral cerebellar hypometabolism (CCH) is a well established remote functional effect of cerebral damage. Because CCH has been reported to be reversible in acute stroke in at least some patients, the value of cerebellar metabolic asymmetry (CbMA; a reflection of the degree of CCH) as a predictor of stroke outcome has been assessed. Measurements of cerebellar oxygen consumption were performed by positron emission tomography (PET) in 16 patients within 5-30 hours of onset of their first ever middle cerebral artery territory stroke, and again 13-56 days later in 12 survivors. The neurological state was quantified at the time of each PET study and at day 60, with both the Mathew and Orgogozo scales. In the early PET study, the CbMAs ranged from around 0% to nearly 50% (individually significant at p < 0.05 in 9/16 patients) but were neither strongly nor consistently correlated with neurological outcome or recovery at day 60. Similarly, the changes in CbMAs from the early to the late PET study were not correlated with the concomitant neurological evolution. At the late PET study, however, there were excellent positive correlations between CbMAs and both neurological status and size of infarction (assessed by CT in the chronic stage). The correlation with neurological status was explained by the correlation with size of infarction. The poor predictive value of CbMAs in the early PET study may be partly because the cerebral metabolic disturbance might still be evolving at this early stage in some cases. Despite this lack of a strong quantitative link between CbMAs at the early PET study and outcome, the outcome was good in all the patients who did not exhibit significant CCH, suggesting that lack of CCH may predict good outcome in acute middle cerebral artery stroke.

Aged↗
PubMed1994

[Unusual triggering circumstance of benign acute cerebral angiopathy; link with exertion cephalalgia?].

Immediately following a scream of fear, a sixty-year old woman complained of severe bilateral headache which relapsed several times over the following month during exercise. There was no history of sympathomimetic drug intake. The work-up was normal save for minimal subarachnoid bleeding and the angiogram showed a disseminated "sausage-string" appearance over all cerebral arterial territories, without aneurysm. The unusual triggering event in this case and the subsequent recurrence of headache in relation to exercise lead us to discuss possible links between the clinical entity of "Isolated benign cerebral angiopathy" and exertional headache.

Cerebral Arteries↗
PubMed1994

[Endoscopic retropubic colpopexy for stress urinary incontinence in women (Stamey's operation). 55 cases].

Fifty five women with a mean age of 59 years, suffering from urinary stress incontinence (U.S.I.), were treated by endoscopic percutaneous cervicocystopexy (Stamey's operation), 39 patients (71%) suffered from pure U.S.I. and 16 (29%) presented a combination of stress and urge incontinence. Bonney's manoeuvre was positive in every case. With a mean follow-up of 21.5 months, 30 patients (58.8%) were completely continent, 9 (17.6%) presented occasional incontinence with intense effort, 12 (23.5%) were failures and 4 patients were lost to follow-up. The complications were minimal. The results were less favourable in patients with a history of pelvic surgery, particularly for correction of U.S.I., associated urge incontinence, detrusor hyperactivity or low urethral closure pressure, although one half of the patients in this group were nevertheless cured. Stamey's operation is a simple, reliable, easily reproducible technique which gives good results at the cost of low morbidity, short hospital stay and a low cost.

Adult↗
PubMed1993

PET imaging of cerebral perfusion and oxygen consumption in acute ischaemic stroke: relation to outcome.

We used positron emission tomography (PET) to assess the relation between combined imaging of cerebral blood flow and oxygen consumption 5-18 h after first middle cerebral artery (MCA) stroke and neurological outcome at 2 months. All 18 patients could be classified into three visually defined PET patterns of perfusion and oxygen consumption changes. Pattern I (7 patients) suggested extensive irreversible damage and was consistently associated with poor outcome. Pattern II (5) suggested continuing ischaemia and was associated with variable outcome. Pattern III (6), with hyperperfusion and little or no metabolic alteration, was associated with excellent recovery, which suggests that early reperfusion is beneficial. This relation between PET and outcome was highly significant (p < 0.0005). The results suggest that within 5-18 h of stroke onset, PET is a good predictor of outcome in patterns I and III, for which therapy seems limited. The absence of predictive value for pattern II suggests that it is due to a reversible ischaemic state that is possibly amenable to therapy. These findings may have important implications for acute MCA stroke management and for patients' selection for therapeutic trials.

Aged↗
PubMed1993

CO2 reactivity in the ischaemic core, penumbra, and normal tissue 6 hours after acute MCA-occlusion in primates.

Testing vasoreactivity with CO2 or Diamox is a common diagnostic procedure for the study of haemodynamics in stroke patients. CO2 reactivity (CO2R) was tested in 5 baboons six hours after permanent occlusion of the left middle cerebral artery (MCA) in order to attain new insights into interpretation of vasoreactivity tests. Using the microsphere method, cerebral blood flow (CBF) was determined in the various vascular territories as well as in the centre of the ischemia, the penumbra and the remaining MCA-tissue. CBF decreased significantly in the affected MCA in all animals and in addition in the contralateral cerebellum in one animal (p < 0.05). In addition, the left anterior cerebral artery (ACA) demonstrated a similar decrease. During hypercapnia CBF increased in all areas with the exception of the left, occluded MCA territory. Thus CO2 enhanced the difference between ischaemic and non-ischaemic tissue (i.e., tissue with diaschisis). Mean CO2 R was 3.37 ml/100 g/min/mmHg in the right MCA, 0.16 in the left. While the left ACA demonstrated a decreased perfusion during normocapnia in a similar range to the MCA territory, only CO2R was able to identify precisely the territory of the occluded vessel. CO2 R was zero or negative in the ischaemic core, close to zero in the penumbra and profoundly decreased in the remaining MCA tissue. The overall CO2 R of the MCA was almost zero, suggesting vasoparalysis in response to hypercapnia in the core and penumbra and exhausted CO2 R even in non-infarcted, non-penumbral tissue. One animal displayed a negative CO2 R equivalent to an intracerebral steal-phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Positron emission tomographic studies of [11C]MDL 72222, a potential 5-HT3 receptor radioligand: distribution, kinetics and binding in the brain of the baboon.

The drug MDL 72222, a selective 5-HT3 receptor antagonist, was labelled with 11C and evaluated for distribution kinetics in brain and in vivo binding to 5-HT3 receptors using cold MDL 72222 challenge and positron emission tomography (PET), in three anaesthetized baboons. After tracer doses of [11C]MDL 72222 (i.v. bolus), 11C radioactivity was equally partitioned between plasma and blood cells and readily crossed the blood-brain barrier; it was distributed heterogeneously into 17 different structures of the brain. The kinetic curves for 11C in tissue showed a rapid initial uptake, followed by a slower ascending phase, up to about the twentieth minute and by a plateau, until the end of experiment (90 min). The plateau values indicated marked uptake in brain which, however, varied according to the region considered. In inhibition studies with cold MDL 72222 (1 mg.kg-1) as pretreatment, co-injection or displacement, no clear-cut effects on the kinetics of [11C] MDL 72222 in brain were detected in any region, including those known to be rich in 5-HT3 receptors. These observations suggest that specific binding to 5-HT3 receptors was not detectable in brain in vivo, because of the high lipophilicity (thus a great capacity for non-specific binding) of MDL 72222. These negative findings may also result from both the possible suboptimal affinity of MDL 72222 for 5-HT3 receptors in vivo and the relatively low density of 5-HT3 receptors present only in selected areas of the mammalian brain. This study is a step in the search of selective 5-HT3 receptor radioligands, adequate for in vivo applications. Slow clearance of [11C]MDL 72222 from brain tissue in baboons, should be accounted for in clinical pharmacokinetic investigations for optimal posology considerations.

Animals↗
PubMed1993

Determination of 18F-fluoro-2-deoxy-D-glucose rate constants in the anesthetized baboon brain with dynamic positron tomography.

We have determined the rate constants (ki*) of 18F-fluorodeoxyglucose (FDG) in the unlesioned baboon brain, for use in positron emission tomography (PET) measurements of glucose utilization. In contrast to earlier reports, we used a radiosynthesis which guarantees production of FDG essentially uncontaminated by fluorodeoxymannose, and an improved determination of ki* by (1) direct measurement of the time-shift between bolus arrival in femoral arterial plasma and brain, (2) rapid initial PET frames, and (3) extended data acquisition (up to 180 min). Young adult baboons were studied under anesthesia with either phencyclidine or etomidate. The FDG time-activity curves obtained from temporal grey matter showed a consistent decline after about 80 min, indicating true product loss. Three-compartment modelling was performed for increasing fitting intervals (20-120 min) with both a 5-parameter (K1*-k4*, and vascular volume (Vo)) and a 4-parameter (K1*-k3*,Vo) model. With the latter, both the calculated FDG net clearance ((K* = K1*.k3*/(k2* + k3*)) and the fitted kinetic constants were dependent on fitting interval, i.e., they showed sustained unstability. With the former, the constant k4*, which presumably represents dephosphorylation, was overestimated and unstable for short fitting times (presumably due to heterogeneous brain compartments in the sample tissue), but stabilized at approximately 0.01 min-1 for fitting times > or = 80 min; K1*-k3* and K* were also stable after this time. These findings were identical for both anesthetic regimen. Thus, in the anesthetized baboon, the FDG ki* values can be reliably determined based on an adequate PET acquisition paradigm and with a model that incorporates k4* and > or = 80 min time-activity data.

Anesthesia↗
PubMed1993

PET study of changes in local brain hemodynamics and oxygen metabolism after unilateral middle cerebral artery occlusion in baboons.

Local cerebral hemodynamics and oxygen metabolism were measured by positron emission tomography (PET) with the oxygen-15 (15O) steady-state method in baboons, immediately before (T0), 1 (T1), and 3-4 (T2) h after permanent middle cerebral artery occlusion (MCAO). At T1, there was a marked fall in both cerebral blood flow (CBF) and the CBF/cerebral blood volume (CBV) ratio in the occluded territory; these changes were sustained at T2, indicating stable reduction in cerebral perfusion pressure and lack of spontaneous reperfusion within this time range. Compared with preocclusion conditions, the oxygen extraction fraction (OEF) in the occluded territory was elevated at both T1 and T2, indicative of a persistent oligemia/ischemia for up to 3 h after MCAO. At T2, however, this OEF increase had lessened, concomitantly with a decline in cerebral metabolic rate of oxygen (CMRO2). This impairment of oxidative metabolism occurred earlier in the deep, compared with the cortical, MCA territories; in the latter, the CMRO2 was essentially preserved at T1 and only moderately reduced at T2, possibly suggesting prolonged viability. Finally, no significant changes in CBF or CMRO2 were observed in the contralateral MCA territory in this time range after MCAO. Despite methodological limitations (mainly partial volume effects related to PET imaging, which may have resulted in an underestimation of true changes and an overlooking of heterogeneous changes) our study demonstrates the feasibility of the combined PET-MCAO paradigm in baboons; this experimental approach should be valuable in investigating the pathophysiology and therapy of acute stroke.

Animals↗
PubMed1993

Extraperitoneal endosurgical lymphadenectomy with insufflation in the staging of bladder and prostate cancer.

A new technique of endosurgical pelvic lymph node dissection was performed for the staging of 10 prostate and 8 bladder cancers. The technique, involving an exclusive extraperitoneal space development with CO2 insufflation, is described in detail. Using the standard endosurgical (laparoscopic) equipment, we performed a complete bilateral ilio-obturator lymph node dissection in 15 patients (83%). In the remaining three patients, because of technical difficulties, only unilateral dissection was performed. The average operating time was 84 minutes. Morbidity was low (one instance of sepsis). Prospective assessment of CO2 homeostasis showed that arterial CO2 pressure (PaCO2) increased significantly but could be controlled by increasing minute ventilation output. Our results show that perioperative assessment of end-tidal CO2 partial pressure is necessary and sufficient for the adaptation of minute ventilation output. Two patients with prostate cancer had positive nodes. No intraoperative or postoperative morbidity related to the procedure was observed in patients submitted to radical surgery. Extraperitoneal endosurgical pelvic lymphadenectomy with CO2 insufflation is a rapid, safe, and effective method in the staging of urologic pelvic malignancies and represents an alternative to traditional open surgery as well as to conventional transperitoneal laparoscopic lymphadenectomy.

Carbon Dioxide↗
PubMed1993

Loss of brain 5-HT2 receptors in Alzheimer's disease. In vivo assessment with positron emission tomography and [18F]setoperone.

Using [18F]setoperone and positron emission tomography (PET), alterations in serotonergic 5-HT2 receptor binding were studied in cerebral cortex of nine unmedicated patients with probable Alzheimer's disease and 37 healthy controls. The kinetics of unchanged radioligand in plasma and 18F-radioactivity in blood and brain were obtained for 90 min following tracer injection. The specific binding of [18F]setoperone to 5-HT2 receptors in the cerebral cortex was quantitated by subtraction using cerebellum as reference. In controls, a significant reduction in specific binding was associated with age and similar linear regression slopes were obtained in all the cortical regions studied. No significant difference was observed between patients with Alzheimer's disease and age-matched controls in the injected mass of setoperone, percentage of unmetabolized [18F]setoperone in plasma, 18F-radioactivity in blood fractions and cerebellar 18F-radioactivity concentration, indicating similar non-specific brain kinetics and metabolism of the radioligand. In contrast, there was a significant reduction in specific [18F]setoperone binding in the cerebral cortex in patients with Alzheimer's disease relative to control values (temporal, 69%; frontal, 69%; parietal, 55%; temporo-parietal, 54%; occipital cortex, 35%). The results demonstrate that the loss in 5-HT2 receptor binding in the cerebral cortex of patients with Alzheimer's disease, long documented by post-mortem studies, can now be assessed in vivo using PET.

Aged↗