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Biomedical subjects

G Fink

Publications and source records attributed to G Fink.

At least 91 records · Page 5Linked to original sources

An interactive technique for three-dimensional image registration: validation for PET, SPECT, MRI and CT brain studies.

UNLABELLED: A multipurpose three-dimensional registration technique was validated with PET, SPECT, CT and MRI scans, which had been obtained under normal clinical conditions. In contrast to fully automated procedures, this coregistration method is highly interactive, which has the advantage that it does not impose rigid restrictions by data type and by alterations in normal anatomy or brain function resulting from disease. METHODS: Basically, a computer program provides a variety of tools to examine the accuracy of coregistration visually and to specify necessary translations and rotations in all three dimensions. Tools and criteria to accept coregistration were applied according to a standardized protocol. Reproducibility was assessed with five independent users on nine pairs of image sets. In two pairs of these image sets, coregistration was repeated three times by each user. RESULTS: Depending on the resolution of the images involved, the reproducibility of translation distances ranged from 0.32 to 2.22 mm (s.d.) and of rotation angles from 0.32 to 1.70 degrees. It was always much smaller than the point-spread full-width half maximum of the device with the lower resolution. The accuracy of coregistration was examined using two arbitrarily misplaced image sets. Interindividual and intraindividual variance were similar, which suggested that the influence of subjectivity was not significant. Average displacements after coregistration were 0.43 and 0.29 mm or less for PET and MRI data, respectively, which indicated the absence of a systematic bias. CONCLUSION: The results indicate the high reproducibility and accuracy of this three-dimensional coregistration technique, which is comparable or superior to those of automated techniques and methods based on external artificial landmarks.

Brain↗

The VIP2 receptor: molecular characterisation of a cDNA encoding a novel receptor for vasoactive intestinal peptide.

We have cloned and sequenced a cDNA (RPR4) encoding a new member of the secretin/calcitonin/parathyroid hormone (PTH) receptor family. RPR4 was identified by PCR of rat pituitary cDNA, and a full-length clone was isolated from a rat olfactory bulb cDNA library. When RPR4 was functionally expressed in COS 7 cells, cyclic adenosine monophosphate (cAMP) production was stimulated by vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptides (PACAP-38 and PACAP-27) and helodermin, with equal potency. Peptide histidine isoleucine (PHI) and rat growth hormone releasing hormone (rGHRH) also stimulated cAMP production at lower potency. This suggests that RPR4 encodes a novel VIP receptor which we have designated the VIP2 receptor. In situ hybridisation showed that mRNA for this receptor was present mainly in the thalamus, hippocampus and in the suprachiasmatic nucleus.

Amino Acid Sequence↗

Molecular cloning and expression of a cDNA encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP).

We have cloned and sequenced a novel cDNA (RPR7) encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP). RPR7 was identified by PCR of rat pituitary cDNA, and full-length clones were isolated from a rat olfactory bulb cDNA library. When expressed in COS cells, RPR7 was functionally coupled to increases in intracellular cyclic adenosine monophosphate (cAMP) in response to stimulation by PACAP-38, PACAP-27, vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI). The order of potency of these ligands was PACAP-38-PACAP-27 > VIP > PHI, suggesting that the receptor corresponds to the pharmacologically characterised PACAP Type I receptor.

Amino Acid Sequence↗

Assessment of exercise capacity in asthmatic children with various degrees of activity.

Physical fitness in a group of 49 stable asthmatic children was determined by an incremental exercise test. Thirty-one normal children served as a control group. The asthmatic children were divided into three groups. Group 1 was comprised of 16 children who actively participated in organized sports, Group 2 of 16 children who did not participate in organized sports but who engaged in free-play, and Group 3 of 17 children with a sedentary life-style who avoided even free-play. The results of cardiopulmonary evaluation before and after maximal incremental exercise testing have shown that Groups 1 and 2 behaved like the control group and their physical fitness was similar. Group 3 whose life-style was sedentary had poor physical fitness as compared to the other asthmatics and to the control group. This was the result of poor cardiovascular conditioning and was unrelated to the respiratory limitation. We conclude that poor physical fitness in asthmatic children is the result of a sedentary life-style and can be potentially normalized.

Adolescent↗

The effects of adrenalectomy and ovariectomy on the behavioral and hypothermic responses of rats to 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT).

The aim of this study was to determine the effects of sex, corticosterone and oestradiol-17 beta on the hypothermia and motor behavioural syndrome induced by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermia, but not the behavioural syndrome induced by 8-OH-DPAT was significantly greater in female compared with male rats. Adrenalectomy in male rats enhanced the hypothermic response, an effect prevented by corticosterone implants. Ovariectomy significantly attenuated the hypothermia induced by 8-OH-DPAT, an effect prevented by oestradiol-17 beta implants. Neither type of steroid manipulation affected the behavioural syndrome. These results show that sex, corticosterone and oestradiol-17 beta modulate the hypothermic response to 8-OH-DPAT in the rat, with corticosterone and oestradiol-17 beta having opposing effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Glucocorticoid receptor gene expression is unaltered in hippocampal neurons in Alzheimer's disease.

Excessive glucocorticoid levels increase the metabolic vulnerability of hippocampal neurons to a wide variety of insults. Since glucocorticoid hypersecretion occurs in Alzheimer's-type dementia it has been proposed that a primary reduction in hippocampal glucocorticoid receptor expression leads to failure of feedback, hypercortisolemia and hence further neuronal loss. However, we have recently found that lesions of the cholinergic innervation of the hippocampus--known to be severely affected in Alzheimer's disease--increase corticosteroid receptor gene expression in the rat hippocampus. We have now examined both glucocorticoid (GR) and mineralocorticoid (MR) receptor gene expression in individual neurons in human postmortem hippocampus, using in situ hybridization histochemistry in 5 patients with Alzheimer's disease (81 +/- 3 years) and 7 controls (81 +/- 7 years) without neurological disease. The distribution and intensity of MR and GR mRNA expression in the hippocampus of Alzheimer's disease were similar to that in control tissue, with high expression in dentate gyrus and CA2-4, but significantly lower expression in CA1. In a separate group of patients with Alzheimer's disease we found significantly increased 24 h integrated plasma cortisol levels (59% greater than age-matched controls) and reduced cortisol-binding globulin (21% lower). These data do not suggest a primary deficiency of biosynthesis of hippocampal corticosteroid receptors in Alzheimer's disease. The maintenance of hippocampal GR and MR gene expression, in the face of an increased glucocorticoid feedback signal, may reflect loss of the cholinergic innervation.

Aged↗

Positron emission tomography in myotonic dystrophy.

Regional cerebral glucose metabolism (rCMRG1) was studied in three patients with myotonic dystrophy by positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose as the radiotracer. Clinically, all patients presented an organic personality syndrome. Impairment of rCMRG1 was found in all cortical and subcortical regions, particularly in the frontal cortex and the lentiform nucleus. The results suggest that the organic personality changes that occur in myotonic dystrophy reflect widespread cerebral pathology. The metabolic pattern was similar to that seen in normal aging but was qualitatively more severe and is therefore consistent with the classification of myotonic dystrophy as a progeric disease.

Adult↗

The effects of the modified intermittent sequential pneumatic device (MISPD) on exercise performance following an exhaustive exercise bout.

The Lymphapress, a pneumatic sequential intermittent device is recognized as one of the most effective conservative treatments for lymphoedema, due to its effective 'milking mechanism'. This led us to hypothesize that accelerated removal of fatigue-causing metabolites by mechanical massage could improve an athlete's performance capacity. We conducted trials with 11 men who exercised at a constant workload, on a cycle ergometer, until exhaustion. During a 20-min recovery period a new modified pneumatic sequential intermittent device (the MISPD) was applied to the subjects' legs. The men then performed a second constant load exercise bout. Cardiorespiratory parameters were measured during exercise and blood was withdrawn during recovery for the determination of lactate, pyruvate, ammonia, bicarbonate and pH. No difference was found in the blood levels of the 'fatigue causing metabolites' during passive recovery (PR) and recovery with the MISPD (MR). However, the MISPD effected a 45% improvement in the subjects' ability to perform the subsequent exercise bout. The accumulation of fluid in the interstitial space after exercise and its disappearance after the use of the MISPD offers one possible explanation for these results, although psychological effects cannot be discounted.

Adult↗

Suture granuloma simulating lung neoplasm occurring after segmentectomy.

A suture granuloma was resected which developed after segmentectomy of a squamous cell carcinoma of the lung and radiologically mimicked a neoplasm. This report emphasises that although the appearance of the lesion may be typical for malignancy, the possibility of a benign suture granuloma should be considered, especially if the lesion appears shortly after surgery.

Carcinoma, Squamous Cell↗

External high-frequency ventilation in severe chronic obstructive pulmonary disease.

We studied the effect of external high-frequency oscillation using an oscillator (Hayek oscillator [HO]) on 20 patients with severe chronic obstructive pulmonary disease (COPD). Of the 20 patients, 10 were eucapnic and 10 were hypercapnic. The HO generated frequencies from 60 to 140 cycles/min at an amplitude of 36 cm H2O (-26 to +10) and at an inspiratory/expiratory (I/E) ratio of 1:1. The results show that the HO is a powerful ventilator, reducing end-tidal PCO2 (PETCO2) by 6.7 to 9.1 mm Hg in eucapnic patients and by 6.1 to 7.9 mm Hg in hypercapnic patients. The oxygen saturation increased by 2 to 2.87 percent in the eucapnic patients and by 2.6 to 3.7 percent in the hypercapnic group in the various frequencies. The rate of elimination of CO2 and the levels of PETCO2 achieved within a short time were superior to those reported with other external ventilators. We conclude that the HO can be effectively used in severe COPD and respiratory failure for (1) assisting ventilation, thus replacing intubation and conventional mechanical ventilation, and (2) relieving muscle fatigue in short sessions.

Aged↗

The 11 beta-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides in rats.

Steroid-metabolizing enzymes modulate the effects of androgens on brain differentiation and function, but no similar enzymatic system has been demonstrated for adrenocorticosteroids which exert feedback control on the hypothalamus. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) rapidly metabolizes physiological glucocorticoids (corticosterone, cortisol) to inactive products, thereby regulating glucocorticoid access to peripheral mineralocorticoid and glucocorticoid receptors in a site-specific manner. Using in-situ hybridization, we found expression of 11 beta-OHSD mRNA in neurones of the hypothalamic paraventricular nucleus (PVN) where corticotrophin-releasing factor-41 (CRF-41) is synthesized and from where it is released into hypophysial portal blood. Administration of glycyrrhetinic acid (GE), a potent 11 beta-OHSD inhibitor, decreased CRF-41 release into hypophysial portal blood in the presence of unchanged circulating glucocorticoid levels, suggesting that 11 beta-OHSD regulates the effective corticosterone feedback signal to CRF-41 neurones. These effects of GE were not observed in adrenalectomized animals, demonstrating dependence on adrenal products. In contrast, GE led to two- to threefold increases in arginine vasopressin and oxytocin release into portal blood, effects also dependent upon intact adrenal glands. These results suggest that 11 beta-OHSD in the PVN, and possibly other sites, may represent a novel and important control point of corticosteroid feedback on CRF-41 release in vivo.

11-beta-Hydroxysteroid Dehydrogenases↗

Medial septal cholinergic lesions increase hippocampal mineralocorticoid and glucocorticoid receptor messenger RNA expression.

Loss of the cholinergic innervation of the hippocampus and failure of central (presumably hippocampal) suppressive control of hypothalamic-pituitary-adrenal axis activity are important features of Alzheimer's dementia. We have examined the effects of electrolytic lesions of the medial septal cholinergic innervation on mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA expression in rat hippocampus using in situ hybridization histochemistry. Expression of both MR and GR mRNA was significantly increased in a subregions of the hippocampus, but not neocortex, with the greatest increase in the CA1 area for MR mRNA and dentate gyrus for GR mRNA. Since glucocorticoids potentiate the effects of neurotoxins in the hippocampus, the increased expression of receptors following loss of cholinergic inputs in Alzheimer's disease may increase hippocampal neuronal vulnerability.

Acetylcholine↗

[Cardiopulmonary exercise testing in asthmatic patients].

In order to obtain objective information on physical fitness of asthmatic patients, mainly those with severe chronic airway obstruction, an incremental exercise test was carried out in 50 asthmatics. A control group of 48 healthy subjects had similar anthropometric characteristics. The 2 groups achieved similar maximal heart rates: 96.1 +/- 8 of predicted rate in the asthmatics as compared to 98.4 +/- 4 in the controls. Maximum oxygen consumption (VO2max), anaerobic threshold and oxygen pulse (VO2/hr) were significantly lower in the asthmatics. While in mild and moderate cases performance was limited by the cardiovascular system, in severe asthmatics the limitation was respiratory. There was no correlation between severity of airway obstruction and cardiac parameters such as oxygen pulse, anaerobic threshold and VO2max. On the other hand, there was good correlation between FEV1% and the dyspnea index (Ve/MVV%). The latter was less than 60% in all asthmatics when measured during exercise testing at 75% of maximal predicted heart rate. It is thus possible for an asthmatic to engage in physical activity of the intensity that can potentially improve his physical fitness. We assume that reduction in cardiac parameters is a result of poor physical fitness related to prolonged inactivity, quite common in asthmatics as a result of inappropriate physical education.

Asthma↗

The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls.

The aims of this study were to determine whether the administration of cortisol has a significant effect on mood in patients with depression and whether the effects of cortisol on changes in plasma hormone concentrations are like those of synthetic corticosteroids. Twelve patients had major depression and one each had dysthymic disorder and a depressive adjustment disorder. Five were male and nine were female. All were in-patients. Eight normal subjects, two females and six males, were used as controls. Basal beta-endorphin concentrations were 2- to 3-fold higher in depressed patients than in control subjects, but there were no significant differences between the patient and control groups in the basal (pre-infusion) plasma concentrations of ACTH, cortisol, growth hormone or prolactin. Cortisol, but not saline infusion resulted in a significant improvement in self rated mood. Surprisingly, cortisol infusion at first increased plasma beta-endorphin concentrations. At later times after cortisol infusion, plasma beta-endorphin concentrations decreased as did the plasma concentrations of ACTH and growth hormone; prolactin levels were increased. These results show (i) that cortisol infusion raises mood significantly in major depression, (ii) that plasma beta-endorphin concentration is a potential marker of major depression (iii) that rather than blunting of corticosteroid effects, responses to cortisol may even be enhanced in depressive illness. The unexpected, initial increase in beta-endorphin stimulated by cortisol, suggests that the action of cortisol is not simply one of negative feedback inhibition, but may involve mineralocorticoid, as well as glucocorticoid receptors.

Adrenocorticotropic Hormone↗

Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women.

The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity.

Belize↗