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Biomedical subjects

A Kling

Publications and source records attributed to A Kling.

At least 19 recordsLinked to original sources

Dosimetry at the Portuguese research reactor using thermoluminescence measurements and Monte Carlo calculations.

This work presents an extensive study on Monte Carlo radiation transport simulation and thermoluminescent (TL) dosimetry for characterising mixed radiation fields (neutrons and photons) occurring in nuclear reactors. The feasibility of these methods is investigated for radiation fields at various locations of the Portuguese Research Reactor (RPI). The performance of the approaches developed in this work is compared with dosimetric techniques already existing at RPI. The Monte Carlo MCNP-4C code was used for a detailed modelling of the reactor core, the fast neutron beam and the thermal column of RPI. Simulations using these models allow to reproduce the energy and spatial distributions of the neutron field very well (agreement better than 80%). In the case of the photon field, the agreement improves with decreasing intensity of the component related to fission and activation products. (7)LiF:Mg,Ti, (7)LiF:Mg,Cu,P and Al(2)O(3):Mg,Y TL detectors (TLDs) with low neutron sensitivity are able to determine photon dose and dose profiles with high spatial resolution. On the other hand, (nat)LiF:Mg,Ti TLDs with increased neutron sensitivity show a remarkable loss of sensitivity and a high supralinearity in high-intensity fields hampering their application at nuclear reactors.

Algorithms↗

Decreased density of serotonin 5-HT2A receptors in rheumatoid arthritis.

BACKGROUND: Animal studies have indicated that 5-HT2A receptors could play a role in arthritic diseases. OBJECTIVE: To analyse the binding properties of 5-HT2A receptors in patients with rheumatoid arthritis. METHODS: Using a radioactive binding assay, 43 patients with rheumatoid arthritis were compared with 49 sex and age matched controls for density and affinity (measured as Bmax and Kd) of 5-HT2A serotonin receptors. Genotyping, using polymerase chain reaction, was undertaken to exclude the possibility that differences in the genetic polymorphism T102C for the 5-HT2A receptor determine differences in receptor density. RESULTS: Mean of Bmax of 5-HT2A receptors in rheumatoid patients was significantly lower than in controls, at 45.3 v 57.4 fmol/mg protein (p = 0.004), but there was no significant difference in Kd. The T102C receptor polymorphism genotypes showed a skewed distribution between the two groups. Even when adjusted for this, there was a significant difference in Bmax between the groups. CONCLUSIONS: The density of 5-HT2A serotonin receptors in patients with rheumatoid arthritis is markedly reduced. This could either reflect a difference involved in the susceptibility to the disease or be a secondary effect of the disease.

Aged↗

Thermoluminescence dosimetry of a thermal neutron field and comparison with Monte Carlo calculations.

The characteristics of thermoluminescence dosemeters (TLDs) regarding the determination of photon and neutron absorbed doses were investigated in a thermal neutron beam. Harshaw TLD-100 (LiF:Mg,Ti) and TLD-700 (7LiF:Mg,Ti) were compared with similar materials from Solid Dosimetric Detector and Method Laboratory (People's Republic of China). Harshaw TLD-700H (7LiF:Mg,Cu,P) and aluminium oxide (Al2O3:Mg,Y) from Hungary were also considered for photon dose measurement. The neutron sensitivity of the investigated materials was measured and found to be consistent with values reported by other authors. A comparison was made between the TL dose measurements and results obtained via conventional methods. An agreement within 20% was obtained, which demonstrates the ability of TLD for measuring neutron and photon doses in a mixed field, using careful calibration procedures and determining the neutron sensitivity for the usage conditions.

Aluminum Oxide↗

Sepsis as a possible adverse drug reaction in patients with rheumatoid arthritis treated with TNFalpha antagonists.

BACKGROUND: Clinical improvement during the treatment of rheumatoid arthritis (RA) with the TNFalpha antagonists has been well documented. Our knowledge of uncommon adverse drug reactions (ADRs) with these new drugs is more restricted. Concerns have been raised that these types of drugs could cause an increased frequency of infections, and already existing infections are named as contraindications in the product labels. METHODS: In Sweden, it is compulsory for healthcare professionals with permission to prescribe drugs to report suspected ADRs to the regulatory authority, the Medical Product Agency (MPA). At the 6 regional centers that are established in Sweden, a preliminary causality assessment is made and the data is transferred online to a database. RESULTS: Between January 1, 1999, and June 30, 2003, 29 cases of sepsis were reported as suspected adverse effects caused by drugs. Seventeen of these cases concerned TNFalpha antagonists. The MPA has received 3 reports of septicemia in patients from Northern Sweden treated with the TNFalpha antagonist etanercept. In submitting these reports, factors that can contribute to susceptibility and to more fatal courses of serious infections are taken into consideration. Demographic and pharmaceutical factors as well as risks from predisposing conditions are discussed in connection with the cases in this report. CONCLUSION: There is a need for more information to physicians to be aware of sepsis as a possible and serious ADR during treatment with TNF antagonists, and that patients with predisposing diseases or those who do not regularly visit their rheumatologist could be at higher risk.

Journal Article↗

Radionuclide production for therapeutic radiopharmaceuticals.

A fundamental task within the framework of a project searching for new radiopharmaceuticals for systemic therapy was the evaluation of the capabilities of the Portuguese Research Reactor (RPI) for the production of several important radionuclides. The feasibility of producing 64Cu, 77As, 153Sm, 165Dy, 166Ho, 170Tm, 177Lu, 186Re, 199Au and 111Ag in useful quantities was evaluated for the present RPI operation schedule (12 h cycles) and for continuous operation. The main evaluation criteria are expressed in terms of specific activity for continuous irradiation and/or 12 h cycle and the use of natural or enriched targets if necessary. Selected samples were irradiated and a comparison between measured activities and values calculated according to the irradiation schedule and using the same software was performed.

Beta Particles↗

Increased regional cerebral perfusion by 99mTc hexamethyl propylene amine oxime single photon emission computed tomography in post-traumatic stress disorder.

OBJECTIVE: Because of the treatment resistance and chronic affective lability of many post-traumatic stress disorder (PTSD) patients and the hypothesized association of these behaviors with temporal and limbic structures, a study was conducted to determine whether these patients would exhibit alterations in regional cerebral perfusion in the temporal and limbic regions compared with age-matched normal volunteers at rest. METHOD: We studied 17 patients using 99mTc hexamethyl propylene amine oxime single photon emission computed tomography. Seven of the patients were on a selective serotonin reuptake inhibitor, five were on a tricyclic antidepressant, and five were on no medication at the time of the study. Patients were compared with eight age-matched normal controls. RESULTS: All PTSD patients showed a relative increase in regional cerebral perfusion in the anterior and posterior cingulate regions bilaterally, the right temporal and parietal regions, the right caudate/putamen region, and the left orbital and hippocampal regions compared with the control group. When the group of PTSD patients who were free of medication were compared with the control group, increased regional cerebral perfusion was found in the right and left caudate/putamen regions and the right orbital and anterior cingulate cortex bilaterally. CONCLUSIONS: PTSD is associated with increased regional blood flow in limbic areas and the right temporal and parietal cortex compared with age-matched normal volunteers.

Adult↗

Discovery and synthesis of (S)-3-[2-(3,4-dimethoxyphenyl)ethoxy]-2- (4,6-dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 302872), a novel orally active mixed ET(A)/ET(B) receptor antagonist.

Structural variation of the endothelin A-selective antagonist (S)-3-methoxy-2-(4,6-dimethoxypyrimidin-2-yloxy)-3, 3-diphenylpropionic acid (LU 135252) led to analogues which retain ET(A) affinity but exhibit substantial ET(B) affinity as well. The most active derivative obtained is (S)-3-[2-(3, 4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yloxy)- 3, 3-diphenylpropionic acid (LU 302872), which can be prepared in enantiomerically pure form in eight steps via an acid-catalyzed transetherification. It has a K(i) = 2.15 nM for binding to the ET(A) receptor and a K(i) = 4.75 nM for binding to the ET(B) receptor, is orally available, and antagonizes the big ET-induced blood pressure increase in rats and the big ET-induced bronchospasm in guinea pigs each time at a dose of 10 mg/kg.

Administration, Oral↗

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

Adolescent↗

Gender differences in sexual fantasy and behavior in a college population: a ten-year replication.

This report is a replication of a study conducted 10 years ago by Person et al., investigating gender differences in sexual behaviors and fantasies in a college population. We found that men continue to fantasize more than women, but the gender differences have narrowed. Recent sexual experiences of our population show a trend toward an increase in gender differences, and there is a greater correlation between sexual fantasy and experiences in women than in men. As in Person's study, we did not find that men had more aggressive/sadistic fantasies than women.

Adult↗

Effect of age and strain on working memory in mice as measured by win-shift paradigm.

Working memory is disrupted in Alzheimer's disease and stroke; therefore, any therapeutic drug should restore deficits in working memory. The win-shift foraging paradigm has been demonstrated to be a model of working memory in rats. In the present study, this paradigm was adapted to mice because of the greater ease and economy of testing potential drugs in mice and the wider availability of strains of aged mice with naturally occurring working memory deficits. This study has demonstrated strain differences in the working memory trace and that age induces a deficit that can be detected at 11 months of age in mice. Tacrine and physostigmine enhance the memory trace in normal mice and physostigmine can reverse age-induced working memory deficits in subjects with mild and moderate deficits but not in subjects with severe deficits.

Aging↗

[Incidence of the detection of erythrocyte antibodies in relation to screening test cells].

A variety of antibody screening tests are available to detect immunization in patients' sera. However, antibodies can be observed only if corresponding antigens are present on test cells used by an antibody screen. By comparing available test cell kits of different manufacturers we revealed various specificities of antigens present or absent on these cells. Using by an antibody screen Wr(a+), Co(b+) and Kp(a+) test cells additionally to available test cells, we detected in 1000 sera of patients 13 anti-Wr(a) and 1 anti-Co(b) besides 17 antibodies with different specificities.

Autoantibodies↗

EEG power variation in schizophrenic subgroups: effects of emotionally salient stimuli.

Eighteen unmedicated chronic schizophrenic patients and 13 normal controls were tested in a paradigm designed to examine functional changes in electroencephalographic (EEG) activity following presentation of emotionally salient auditory stimuli and control tones. Five standard bands of EEG spectral power were examined at bilateral frontal and temporal surface recording sites. The schizophrenic subjects were assigned to diagnostic subgroups on the basis of DSM-III-R criteria following independent clinical examination by two staff psychiatrists. Those subjects who met DSM-III-R criteria for paranoid schizophrenia were assigned to one subgroup (PS subgroup), while those who met DSM-III-R criteria for either residual or undifferentiated schizophrenia were assigned to a second subgroup (R/US subgroup). Analysis of Variance of EEG activity recorded at bilateral frontal (F1 and F2) and temporal (T3 and T4) scalp leads revealed significant diagnosis-related differences in alpha and beta-2 activity at temporal recording sites, and in beta-1 and beta-2 activity at frontal recording sites. Post-hoc tests revealed that significant differences in all four measures occurred in the R/US subgroup, which showed a decrease in temporal alpha and an increase in temporal beta-2 power as compared to controls. These variations in EEG activity appeared to demonstrate a degree of subgroup specificity, as the R/US subgroup also differed significantly from the PS subgroup on most of these measures. Significant subgroup-specific lateralization effects were also observed for temporal lobe delta activity and for frontal lobe beta-1 activity. These findings are interpreted in terms of subgroup-specific alterations in the processing of sensory information in schizophrenia, particularly when such information is emotionally salient. They suggest that subgroup differences in emotional and clinical state may be reflected in differential changes in EEG spectra within the schizophrenic population.

Acoustic Stimulation↗

Clinical and biochemical aspects of depressive disorders: I. Introduction, classification, and research techniques.

The present review focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. In addition to integrating these data, problems and future directions in this research are discussed. The review is presented in three parts. This study, Part I, describes diagnostic classification schemes for depressive disorders, some epidemiological and biological correlates of the classifications, and research techniques for investigating depressive disorders. Research techniques include animal models, human biochemical techniques, and Positron Emission Tomography. In a future issue, Part II will discuss various transmitter/receptor theories of depressive disorders, e.g., noradrenergic, serotonergic, cholinergic, and dopaminergic, GABAergic, and peptidergic theories. Also in a future issue, Part III will discuss treatments for depression and some of the controversies in the field.

Depressive Disorder↗

Response of neurons in the macaque amygdala to complex social stimuli.

The presence of neurons in macaque temporal cortex and amygdala which fire selectively in response to social stimuli has been demonstrated by several investigators. The extent to which such neuronal populations may respond to a broad range of social features, including expressive movements and interactions, has not been fully explored due to the difficulty of presenting such complex stimuli in a controlled fashion. We describe a method for presenting moving segments of macaque behavior, visual and auditory, to animal subjects during single unit recording. The method permits a broad range of stimuli to be used both as probes and as controls. In addition, a novel technique for monitoring eye position in alert macaque subjects is described. We present results from the medial amygdala and adjacent cortex, demonstrating that neurons in these regions respond selectively to features of the social environment.

Amygdala↗

Platelet glutathione peroxidase and monoamine oxidase activity in schizophrenics with CT scan abnormalities: relation to psychosocial variables.

We have previously reported that the activity in platelets of the important antioxidant enzyme glutathione peroxidase (GPx) is inversely correlated with computed tomographic (CT) measures of brain atrophy in a population of patients with chronic schizophrenia, suggesting that low GPx may be a vulnerability factor in those schizophrenic patients with structural brain abnormalities. The significance of this finding has now been explored in a larger clinical population by examining the relation of GPx and CT parameters to psychosocial variables and to the activity of platelet monoamine oxidase (MAO), which has also been reported to be altered in certain schizophrenic populations. In the present study, low platelet GPx and high brain atrophy were found to be associated with DSM-III diagnoses of nonparanoid schizophrenia, a high degree of chronicity, and a predominance of negative symptoms. Contrary to some literature reports, atrophy also correlated with age and length of illness among the schizophrenic patients, although the contribution of these factors was less than that of low GPx, which was itself not age dependent. The ventricle-brain ratio (VBR) and atrophy were highly correlated in a control group of affective disorder patients, but not in the schizophrenic group, where large VBRs were found predominantly in the DSM-III undifferentiated subgroup. The low-GPx/high-atrophy schizophrenic patients had normal platelet MAO levels, and MAO was significantly lower only in the paranoid subgroup, consistent with reported observations. There was no evidence for a neuroleptic-induced effect on either enzyme.

Adult↗