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Biomedical subjects

J C Baron

Publications and source records attributed to J C Baron.

At least 145 records · Page 8Linked to original sources

The occupational risk of cytomegalovirus infection among day-care providers.

We prospectively studied day-care providers at six day-care centers in south-eastern Iowa to determine their occupational risk for primary cytomegalovirus infection and to define epidemiologic risk factors. Ninety-six (38%) of 252 day-care providers were seropositive for cytomegalovirus by latex agglutination at entry into the study. Among 82 seronegative providers available for follow-up, seven seroconversions occurred at only two of the six participating centers, yielding an annualized seroconversion rate of 7.9%. Median time to seroconversion among these providers was 13 months. Using Kaplan-Meier estimates of risk, we determined that the overall risk of seroconversion among providers at various centers ranged from 0% to 22% by 12 months and from 0% to 40% by 16 months. Risk of cytomegalovirus acquisition by providers was independent of race, age, education, the presence of a child at home, or caring for children younger than 2 or 3 years in the day-care center. However, the risk of seroconversion among day-care providers appeared to parallel rates of cytomegalovirus excretion and acquisition among children at each center.

Adult↗

PET studies of [18F]methyl-MK-801, a potential NMDA receptor complex radioligand.

Using positron emission tomography (PET), the potential of 18F-labelled fluoro-methyl-MK-801([18F]FMM) as a radioligand for in vivo studies of the NMDA receptor complex was investigated in baboons. In baseline conditions, there was a slight differential retention of [18F]FMM in cerebral cortex and striatum relative to cerebellum, compatible with specific binding. However, neither pretreatment with pharmacological doses of MK-801 or phencyclidine, nor severe, transient brain hypoxia, were able to clearly alter [18]FMM brain regional kinetics, indicating limited usefulness of this radioligand for in vivo PET investigations of the NMDA receptor.

Animals↗

PET studies of cortical diaschisis in patients with motor hemi-neglect.

Six patients presenting with multimodal, predominantly motor hemi-neglect, were investigated by 15O2 or 18F-DG and PET to study the local cerebral metabolism in intact regions. All had suffered from an acute right-sided (n = 5) or left-sided (n = 1) focal hemispheric lesion (cortico-subcortical and purely subcortical in three patients each). Frontal and parietal cortices on the side of the lesion were significantly hypometabolic relative to the other side in each case, presumably as a result of diaschisis, whereas thalamic hypometabolism was significant in only 4 patients. Compared to absolute metabolic rates for controls, the uninjured hemisphere showed a trend towards hypometabolism. Hence, true hyperactivity of the contralateral hemisphere with respect to the ipsilateral cerebral cortex was not associated with motor hemineglect in this series. On the contrary, hemineglect was associated with a widespread hypometabolism of the entire ipsilateral cerebral cortex in the context of a moderately reduced metabolism of the ipsilateral thalamus and contralateral cerebral cortex. These findings are consistent with the implication of a cortico-subcortical network serving attention.

Aged↗

A comparison of methods for the separation of [11C]Ro 15-1788 (flumazenil) from its metabolites in the blood of rabbits, baboons and humans.

The determination of the percentage of unchanged [11C]Ro 15-1788 with respect to total radioactivity, essential for the pharmacokinetic exploitation of data of blood radioactivity decrease obtained in PET studies, may be carried out with equal results using either an extraction procedure or a TLC method. The analysis of blood samples of various sources (rabbits, baboons, healthy volunteers and anxious patients) and the use of an automatic linear scanner to quantify the radioactive distribution on the TLC plates lead to the conclusion that only [11C]Ro 15-1788 and its acid metabolite [11C]Ro 15-3890 and no other radioactive compound are present in blood at detectable concentration.

Animals↗

Prostate cancer in a 75-year-old man after four decades of testicular androgen deprivation.

In a 75-year-old patient referred for mild obstructive symptoms, physical examination revealed a clinically manifest T2B cancer of the prostate (CaP) involving the right lobe, and bilateral testicular atrophy (TA), right cryptorchidism with TA after orchiopexy at age 10, and left mumps orchitis with secondary atrophy at age 35). Since the age of 35, the patient had a limited sexual life and fathered no children. Transrectal ultrasonography demonstrated a small prostate (21 cm3) with a large hypoechoic zone in the right lobe, an isoechoic left lobe and no sign of capsular/seminal involvement. Three biopsies of the right lobe demonstrated a cancer (Gleason 4-3; score 7) of the right lobe, 3 biopsies of the left lobe showed an atrophic prostate with slight intra-acinar hyperplasia and moderate dysplasia. Morphometric studies showed these findings to be consistent with long-standing androgen deprivation. Serum prostate-specific antigen (PSA) was 8.7 ng/ml, whereas serum testicular androgens were within the castrate value (serum testosterone 0.2 ng/ml, dihydrotestosterone less than 0.05 ng/ml). Serum LH and adrenal androgens were within normal ranges. Bone scan was negative and NMR demonstrated no nodal enlargement. Considering the age of the patient, antiandrogen therapy was given (cyproterone acetate 50 mg t.i.d.). The patient reported marked improvement at 3 and 6 months of follow-up and PSA fell to 1 ng/ml at month 6. However, repeat rectal exams and ultrasonography showed no dramatic modification of the gland. The patient has since been lost to follow-up. Two conclusions may be drawn from this observation. Testicular androgen deprivation at age 35 although leading to prostatic atrophy does not prevent the development of CaP.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[The correlation between the level of prostate-specific antigen and prostate gland volume in the early diagnosis of prostatic cancer].

One hundred and eighty six patients (Pts) presenting with either an abnormal per rectum examination (P.R. suggestive of prostatic cancer (P.Ca) (excluding stage T3) or a prostatic specific antigen (P.S.A.) level greater than or equal to 2.5 ng/ml (radioimmunoassay) were submitted to transrectal ultrasonography (T.R.U.) using a 7 MHz transducer. The prostatic volume (Vol.P) was systematically calculated during T.R.U. and correlated with the P.S.A. level. Six systematic multiple ultrasound-guided biopsies (S.M.U.B.) were performed in the 2 prostatic lobes (3 per lobe) regardless of the result of T.R.U. In the 111 patients in whom the S.M.U.B. were negative, a highly significant correlation (p < 0.001) was observed between the serum P.S.A. level (y) and the prostatic volume (Vol.P): y = (4.13 +/- 0.15 Vol.P) +/- 8.43. In the 75 Pts with P.Ca, the P.S.A./Vol.P correlation was significantly different (p < 0.05) from the straight line of regression with the previous standard deviation. A similar difference in correlation (p < 0.05) was observed in the sub-group of 14 Pts with P.Ca despite normal P.R. and T.R.U. These results suggest: 1) that there is a correlation between the Vol.P measured by T.R.U. and the P.S.A. level in patients with negative S.M.U.B. 2) that the absence of correlation is highly suspicious of P.Ca and requires S.M.U.B. 3) that there is a 15% incidence of P.Ca in the sub-group of Pts with normal P.R. and T.R.U. which are only detected by the raised P.S.A. not correlated with the volume of the prostate.

Biopsy↗

[Histologic identification of the afferent fibers of the pelvic plexus].

The inferior hypogastric (pelvic) plexus conveys two types of fibres: sympathetic fibres originating in the thoracolumbar sympathetic chain and parasympathetic fibers originating in the sacral anterior rami. By using a histofluorescent stain (glyoxalic acid) and a histochemical stain (thiocholine) in 17 fresh cadavres, we have demonstrated that the sympathetic fibres arise from sacral sympathetic ganglia. These fibres participate in the constitution of the pelvic splanchnic nerves. In this study, we confirm that the inferior roots of the pelvic plexus are not only parasympathetic, but also sympathetic.

Adrenergic Fibers↗

Testing cerebral function: will it help the understanding or diagnosis of central nervous system disease?

The recent introduction of non-invasive tools for the quantitative mapping of cerebral function in humans (e.g. cerebral blood flow measurement and positron emission tomography) in conjunction with detailed in vivo tomographic morphology (computed tomography and magnetic resonance imaging) has led to a fruitful interaction between clinicians and fundamental neuroscientists. This has led to the development of a productive, scientifically sound human neuroscience whose aim is to explore brain function directly in the human subject. With respect to the physiological state, this research has resulted in major findings especially in the fields of visual function, attention, anticipatory anxiety, language, motion and somaesthesia. The study of disease states has resulted in less impressive findings. The investigation of patients with focal brain lesions has revealed time-dependent alterations of cerebral blood flow and energy metabolism in widespread grey matter structures, as a result of disconnection; however, these functional alterations apparently reflect a variety of processes, from Wallerian or retrograde degeneration to reversible or irreversible transsynaptic or transneuronal effects, which makes their interpretation uncertain. Likewise the cellular and neurochemical basis for the recovery of energy metabolism in deafferented brain areas remains speculative. Although several types of metabolic effects due to disconnection are correlated to well-defined neuropsychological/behavioural impairment (and recovery therefrom) unexplained discrepancies exist and their role in individual patients remains obscure. The study of the brain's 'functional reserve' by activation paradigms would presumably shed more light on the clinical/functional brain relationships in disease but such investigations are hampered by unresolved methodological issues such as the choice criteria for the control population (?healthy controls, ?asymptomatic brain-lesioned patients) and task (?pseudo-impaired). There are also complex statistical issues because of the requirement to study single cases as a result of the inter-subject variability in lesion topography, size or duration, as well as in the pattern and degree of behavioural impairment. The design of controlled experimental paradigms in non-human primates, involving controlled lesions and sequential behavioural and PET assessment, may help to resolve some of these issues.

Brain Diseases↗

["Clam" enteroplasty in the treatment of unstable or low compliance bladders].

The treatment of urinary incontinence due to unstable bladder remains difficult. In the case of failure of medical or physiotherapeutic treatments, clam enterocystoplasty represents a major and important therapeutic possibility. The operation consists of frontal section of the bladder to form a bivalve followed by interposition, between the two valves, of a detubed ileal graft in order to increase the functional vesical capacity and to interrupt the transmission of detrusor contraction waves from one valve to the other. 10 patients (7 men and 3 women) suffering from urinary incontinence due to neurogenic unstable bladder (4 cases: 3 meningoceles, 1 operated cauda equina neuroma) or to another cause (6 cases, including one sequela of radiotherapy for prostatic cancer and 5 cases of apparently primary urinary incontinence) underwent enterocystoplasty combined, in the case of neurogenic incontinence (2 cases simultaneously and 2 cases previously), with the insertion of an AMS 800 sphincter. No major complication was observed. 9 patients are continent and 1 had to be reoperated to undergo an augmentation enterocystoplasty (failure of the initial operation due to radiation changes of the bladder), 3 retain a post-voiding residual of about 200 ml but not requiring self catheterisation due to the absence of any repercussions on the upper urinary tract. Lastly, urodynamic studies demonstrated a spectacular increase in compliance and functional capacity of the bladder together with a reduction of the amplitude of intravesical pressure peaks.

Adolescent↗

[Treatment of male urinary incontinence with the AMS 800 sphincter prosthesis: 45 cases].

Urinary incontinence due to sphincter incompetence constitutes a major source of disability. The AMS 800 artificial urinary sphincter allows durable restoration of satisfactory continence in patients who are often unresponsive to any other forms of treatment. 45 men underwent implantation of a peribulbar urethral (40) or pericervical (5) artificial sphincter over a 5-year period. Incontinence was secondary to prostatic surgery in the majority of cases (33). The technique, which is now well defined, consisted of urinary drainage via a bladder catheter for 8 days and activation of the sphincter after 1 month. The mean follow-up is 30 months. 36 (80%) of the patients are continent, including 27 (60%) without revision and 9 (20%) underwent unsuccessful revision resulting in partial or complete removal or permanent inactivation of the prosthesis (sepsis, urethral erosion, defective prosthesis). Strict patient selection, a rigorous implantation technique and standardised management of any incidents are key elements in the success of this procedure.

Adolescent↗

[Slowly progressive apraxia: a MRI and positron tomography in 4 cases].

Four right-handed patients (69, 58 and 68 year-old men; 85 year-old woman) complained of motor difficulties with their left hand (3 cases), or both hands predominant on the left side (1 case). Continuous (1 case) or intermittent (2 cases) myoclonus was noted in the left arm. These disorders gradually progressed for 3 to 10 years. Clinical examination disclosed absence of motor, sensory (except in 1 case), or visual deficit. There were no cerebellar signs, no parkinsonian features (except for mild rigidity in 1 case), and no oculomotor abnormality. On the other hand, neuropsychological examination showed evidence of visuo-constructive apraxia in all cases, dressing apraxia in 3/4 cases and writing impairment in 3/4 cases. There was no amnesia, no aphasia and no intellectual impairment. MRI showed atrophy of the parietal areas, predominant on the right side. A positron emission tomography study was performed in all cases, and twice in 1 case. Cortical energy metabolism was measured using either 18 F-fluorodeoxyglucose or 15 O-Oxygen, to calculate the cerebral metabolic rate of glucose (CMRglu) or oxygen (CMRO2) respectively. Cortical metabolism was significantly decreased in the whole cortex of the right hemisphere in 3 cases, and was also reduced in the cortex of the left hemisphere, significantly in 1/3 studied planes. Moreover, regional metabolic indices (CMRO2 or CMRglu/cortex) showed a significant decrease in both the right and left posterior associative areas (temporo-parieto-occipital cortex), predominantly marked on the right side in 3 cases, indicating bilateral cortical dysfunction. At follow-up, one patient became progressively demented, another had visuo-spatial disorders indicating a lesion of both parietal areas. The relationships of our cases with the slowly progressive apraxia syndrome and with corticobasal degeneration are discussed.

Aged↗

Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations.

In 41 patients with progressive supranuclear palsy (PSP) that was diagnosed on the basis of eight clinical criteria (25 patients with all eight criteria [probable PSP] and 16 with six or seven criteria [possible PSP]), we studied cerebral energy metabolism by using positron emission tomography and the fludeoxyglucose F 18 or the oxygen 15 method. Compared with age-matched controls, each of the cortical and subcortical metabolic values was significantly reduced, with a predominance in the frontal cortex, in both groups of patients with probable and possible PSP, without a difference between these two groups, suggesting similar underlying disease. The frontal metabolic value decreased with disease duration, but the relative frontal hypometabolism (expressed as the fronto-occipital metabolic ratio) was apparently already present in the early stages of the disease. The parkinsonian motor score was correlated with the caudate and thalamic metabolic values. The intellectual deterioration index was significantly correlated with both the frontal and the nonfrontal metabolic values. Finally, the frontal neuropsychological score was significantly correlated with only the fronto-occipital metabolic ratio. Hence, in PSP, a degenerative brain disease with subcortical lesions, the prominent frontal lobe-like syndrome essentially depends on the relative hypometabolism of the frontal cortex.

Aged↗

Effects of unilateral lesion of the nucleus basalis of Meynert on brain glucose utilization in callosotomized baboons: a PET study.

Prior work has demonstrated that unilateral lesions of the nucleus basalis of Meynert (NbM) in baboons induce a marked reduction in glucose utilization of the ipsilateral cerebral cortex, linearly proportional to the depression in cortical choline acetyltransferase (ChAT) activity achieved. Unexpectedly, there was also marked hypometabolism of the contralateral cerebral cortex, and glucose utilization recovered gradually on both sides despite persistent deficit in cortical ChAT activity. To investigate the role of the corpus callosum (CC) in this bilateral metabolic effect and subsequent recovery, three baboons were subjected to unilateral electrolytic NbM lesion greater than 3 months following section of the anterior CC. Brain glucose utilization was sequentially studied by positron emission tomography; ChAT activity was measured and histological sections obtained after death. In these animals, the NbM lesion also induced significant metabolic depression over the ipsilateral cortex, proportional to the reduction in ChAT activity. Corpus callosotomy did not prevent the contralateral metabolic effects, suggesting that the latter do not normally operate through the CC. However, there was no significant recovery of glucose utilization, suggesting that, following unilateral NbM lesion, the CC normally mediates, at least in part, the recovery of cortical glucose utilization.

Animals↗

Effects of anterior corpus callosum section on cortical glucose utilization in baboons. A sequential positron emission tomography study.

Cortical glucose utilization was measured under light anaesthesia using positron emission tomography and 18F-fluorodeoxyglucose before and serially after stereotaxic anterior corpus callosum section in 3 adult baboons (Papio papio); in 1 animal needles were introduced but callosotomy was not performed ('sham' operation). Lesion efficacy was verified by x-ray computerized tomography and by postmortem examination which indicated effective anterior two-thirds callosal section in all 3 baboons, as well as a small contusional area in the medial frontal cortex. A two-way layout analysis of variance performed on the regional cerebral metabolic rate of glucose (CMRGlc) data obtained in the frontotemporal, temporal and occipital areas revealed significant effects for both the time and the region factors (P less than 0.00001 for each); the time effects indicated a significant initial metabolic depression (P less than 0.01) at day 11 and 18, and a subsequent recovery (P less than 0.01 to 0.05) at day 98. Average CMRGlc changes from preoperative values at successive studies were -23%, -27%, -17%, -8% and +2%, and -17%, -21%, -10%, -5% and +6% in the 'surgically approached' and the contralateral frontotemporal area, respectively. The frontotemporal/occipital CMRGlc ratio was significantly depressed at days 11, 18 and 32 (P less than 0.01, 0.01 and 0.05, respectively), indicating a transient postoperative alteration in the cortical metabolic pattern. In the 'sham' animal, surgery induced negligible metabolic effects. Our results indicate that effective anterior corpus callosum section induces a transient bilateral depression of cortical metabolism, which predominates in the anterior parts of the brain, while metabolic recovery suggests efficient neuronal adaptation. These functional effects in the cortex may underlie the transient behavioural changes that follow anterior callosotomy in man.

Animals↗

A method for the in vivo investigation of the serotonergic 5-HT2 receptors in the human cerebral cortex using positron emission tomography and 18F-labeled setoperone.

Following previous validation in baboons, we have studied the characteristics of [18F]setoperone as a radioligand for investigating serotonergic 5-hydroxytryptamine2 (5-HT2) receptors in the normal, unmedicated human brain with positron emission tomography (PET); subjects orally pretreated with therapeutic amounts of ketanserin, sulpiride, or prazosin were also studied to evaluate the specificity and sensitivity of [18F]setoperone brain specific binding. In controls (n = 10), the tracer showed a clear-cut retention in both frontal cortex and striatum (known to contain a high density of 5-HT2 receptors) relative to cerebellum (known to be devoid of 5-HT2 receptors). In the seven young controls (20-39 years old), the frontal cortex/cerebellum and striatum/cerebellum ratios increased during the first hour to reach similar values of 2.53 +/- 0.12 and 2.38 +/- 0.11 (mean +/- SEM), respectively, and were essentially stable during the second hour. Pretreatment with ketanserin (a 5-HT2 blocker) significantly reduced the frontal cortex/cerebellum ratio to 0.7-1.0 at 65 min, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. During sulpiride treatment (a D2 blocker), the frontal cortex/cerebellum ratio was not altered, whereas the striatum/cerebellum ratio was significantly, but only partially, reduced. With prazosin pretreatment (an alpha 1-adrenergic blocker), neither the frontal cortex/cerebellum nor the striatum/cerebellum ratio was modified. These data in humans with PET demonstrate that [18F]setoperone labels with high sensitivity and selectivity 5-HT2 receptors in the frontal cortex; in striata, however, binding is to both 5-HT2 and D2 receptors. The deproteinated-to-whole plasma radio-activity concentration ratio increased with time following injection. The mean percentage of intact [18F]setoperone, in deproteinated plasma, was 82, 74, 53, 45, 30, and 22% at 5, 10, 20, 30, 60, and 110 min following injection, respectively. These data indicate that [18F]setoperone (a) is significantly bound to plasma proteins and (b) is significantly metabolized into several labeled metabolites that are much more hydrophilic than setoperone and, hence, presumably do not cross the blood-brain barrier. These results suggest the suitability of [18F]setoperone data for modeling of 5-HT2 receptor binding in brain.

Adult↗

Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study.

The authors compared 16 nondepressed obsessive-compulsive patients (OCS) with 8 normal controls (NC) of similar age for resting-state regional cerebral glucose metabolic rates (rCMRglu) using positron emission tomography with the fluorodeoxyglucose method. OCS were rated for clinical data, and a neuropsychological battery was administered to 14 patients on the day of the scan. Absolute rCMRglu for whole cortex, and normalized prefrontal lateral cortex metabolic rates, were both significantly lower in OCS than in NC. No significant difference between treated (n = 10) and drug-free (n = 6) OCS was found for those variables. OCS were significantly impaired in the neuropsychological tasks assessing memory and attention. The rCMRglu for prefrontal lateral cortex were negatively correlated to Stroop-test subscores. This "frontal-oriented" task assessed the ability of OCS to inhibit immediate but inappropriate responses. These results suggest, in OCS, a modification of the general activating systems of cortical function and a relationship between the lateral prefrontal rCMRglu decrease and a selective attention deficit.

Adult↗