There is only sparse and ambiguous information about circadian and pulsatile secretion features of the hypothalamus-pituitary-adrenocortical system in depression. We studied 15 severely depressed ...(Hamilton Depression Scale 30.4 +/- 6.7) male patients (age 22-72 yr; mean, 47.7 +/- 14.8) and 22 age-matched male controls (age 23-85 yr; mean, 53.1 +/- 18.2). Twenty-four-hour blood sampling from 0800-0800 h with 30-min sampling intervals was performed; from 1800-2400 h, blood was drawn every 10 min. Multivariate analysis of covariance, with the covariate being age, revealed mean 24-h cortisol (315.9 +/- 58.5 vs. 188.2 +/- 27.3 nmol/L) and mean ACTH (7.82 +/- 1.94 vs. 5.79 +/- 1.28 pmol/L) to be significantly increased in depressed patients. The frequency of cortisol (2.6 +/- 0.7 vs. 1.3 +/- 1.0 pulses/6 h) and ACTH (2.6 +/- 1.6 vs. 1.6 +/- 1.4 pulses/6 h) pulses during the evening were higher in patients compared to controls. The flattened circadian cortisol variation and reduced time of quiescence of cortisol secretory activity (140 +/- 116 vs. 305 +/- 184 min) in patients suggest disturbances of circadian functions. We conclude that increased hypothalamus-pituitary-adrenocortical activity in depression is related to a greater frequency of episodic hormone release, and we hypothesize that the observed circadian changes might be partly due to altered mineralocorticoid and glucocorticoid receptor capacity and function.
There is compelling evidence for feedback disturbances in the hypothalamus-pituitary-adrenal system associated with human aging as assessed by challenge tests. However, reports about age-related ...changes in human basal activity are ambiguous and to date little is known about changes in the pulsatile features of the HPA system. To investigate these changes we studied twenty-two healthy male and eleven healthy female subjects ranging from 23 to 85 and 24 to 81 years respectively. 24-hour blood sampling with 30 minute sampling intervals was performed. From 18.00 to 24.00 hours blood was sampled every 10 minutes for analysis of pulsatile features of HPA activity. Statistical analysis revealed that age in particular had major effects upon basal HPA-system activity: there was a significant age-associated increase in minimal (p < 0.0001) and mean (p < 0.0002) cortisol plasma concentrations, but no alteration in pulsatile features. We found no age-cortisol correlation during daytime, but were able to demonstrate a strong impact of age upon cortisol plasma levels from 20.00 to 1.30 hours. The diurnal amplitude of cortisol (p < 0.0005) and ACTH (p < 0.0006), relative to the 24-hour mean of the hormones, showed an age-associated decline. Additionally, the evening cortisol quiescent period (p < 0.0001) was shortened in the elderly, suggesting increasingly impaired circadian function in aging. Our results suggest an increased basal activity and a flattened diurnal amplitude of the HPA system in the elderly.
We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia.
Forty patients (age: isoflurane 24-62 years; ...sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity.
Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; mean +/- SD P = 0.0001).
The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.
The goal of this study was to clarify pharmacological properties of GABAA receptors in cells of the mouse retinal ganglion cell layer in situ. Spontaneous synaptic currents and responses to exogenous ...GABA were recorded from individual neurons in retinal whole mounts (postnatal days 1-3) or retinal stripe preparations (postnatal days 4-6). Drugs were applied by a fast local superfusion system. Current responses were measured with the patch-clamp technique in the whole-cell configuration. All cells responded to exogenous GABA (average EC50 and Hill coefficient: 16.7 microM and 0.95 respectively) and generated GABAergic synaptic currents in response to elevated KCl. GABA-induced currents of retinal ganglion cells were blocked by bicuculline, picrotoxin and Zn2+, as well as strychnine, and increased by pentobarbital, clonazepam and 3 alpha-hydroxy-5 alpha-pregnan-20-one. In some retinal ganglion cells GABA caused an increase in the frequency of spontaneous synaptic currents, which points to a partially depolarizing action of this traditionally inhibitory neurotransmitter in the neural retina. Our major observation is that acetylcholine and acetylcarnitine blocked or reduced GABAergic inhibitory postsynaptic currents and responses to exogenous GABA. This effect was seen in only a fraction of retinal ganglion cells and occurred in both the undesensitized and the desensitized state of the GABAA receptor. The block was voltage-independent and persisted during coapplication with the nicotinic and muscarinic acetylcholine receptor antagonists D-tubocurarine and atropine. In contrast to GABA-activated Cl- currents, glycine-activated Cl- currents remained unaffected by acetylcholine and acetylcarnitine.
We studied corticosteroid-binding globulin (CBG) in 25 drug-free depressed patients and 33 healthy controls over a wide age-range. CBG was measured at 0800, 1400, 2000 and 2400h in all subjects. ...Analysis of variance (ANOVA) with repeated measurement design revealed a significant effect of gender and time, but not of diagnosis (depressed patients vs healthy controls) or age group ( 50 years). In females, regardless of diagnosis, CBG plasma concentrations were significantly increased, when compared with their male counterparts. Although as a group depressed patients had significantly higher plasma cortisol concentrations (108.0 ± 23.1 vs 70.7 ± 10.9
μg/l), CBG levels did not differ between the two groups. Thus we did not find hypercortisolemia in depression to be paralleled by a decrease in CBG. However, the exaggerated activity of the hypothalamus-pituitary-adrenocortical system in healthy and depressed females is associated with an increase in plasma CBG.
Radioinduced brain cyst: case report Dooms, G; Molitor, P; Boulanger, T ...
Bulletin de la Société des sciences médicales du Grand-Duché de Luxembourg,
2014
1
Journal Article
Recenzirano
We present a case of intraparenchymal radioinduced cyst of the brain observed in our department. It is a rare and relatively benign pathology which is usually treated conservatively or by surgery. We ...emphasize long-term imaging follow up in patients treated by radiosurgery, which can lead to the demonstration of multiple adverse events such as tumefactive cyst formation.
High‐frequency stimulation of the subthalamic nucleus (STN) is a promising therapeutic approach in patients with severely disabling Parkinson's disease (PD). Whereas STN stimulation improves the ...cardinal signs of PD, little is known about the effects of STN stimulation on fine manual skills like handwriting. Therefore, the present study investigated the changes in handwriting during bilateral STN stimulation in 12 patients with advanced PD. Dopaminergic medication was discontinued at least 12 hours before the study. The patients were asked to write a standardized sentence repetitively. Five samples of the patient's script were recorded during effective bilateral STN stimulation and 1 hour after both stimulators had been switched off. The movements of the tip of the pencil were recorded using a digitizing tablet. Handwriting movements were segmented into subsequent up‐ and downstrokes, and a stroke‐based kinematic analysis of handwriting was performed. During high‐frequency STN stimulation, handwriting movements became faster and smoother indicating a partial restoration of an “open‐loop” automatic performance. In addition, STN stimulation gave rise to a significant increase in the mean vertical stroke length demonstrating a stimulation‐related reduction in micrographia. The present data underscores the importance of the STN in “open‐loop” performance of highly skilled sequential hand movements.
There is some evidence that the somatotrophic system in depression, as assessed by basal growth hormone (GH) concentrations and by GH releasing hormone (GHRH) challenge, might be dysfunctional. ...However, the rather limited data have been inconclusive so far and plasma concentrations of both insulin-like growth factor-1 (IGF-I) and binding proteins (IGFBP 1 to IGF BP-6) have not been measured simultaneously in depressed patients. We studied 24 severely depressed patients and 33 healthy controls and estimated 24-hour mean plasma cortisol, six-hour evening mean plasma growth hormone (GH), morning plasma IGF-I, IGFBP 2 and 3 and GH-binding protein (GH-BP). Twenty-four-hour mean cortisol (306 ± 69 vs. 196 ± 30 nmol/l,
p < .001) and IGF-I (157 ± 40 vs. 120 ± 33 μg/l,
p < .01) plasma concentrations were found to be significantly increased in depressed patients, while there was no difference in GH or binding proteins between both groups. MANOVA analysis revealed age and diagnosis to have main effects upon plasma IGF-I. Especially young age and a diagnosis of major depression are associated with higher plasma IGF-I. After treatment only patients in remission had attenuated IGF-I plasma concentrations. We conclude that plasma IGF-I is increased in acutely depressed patients similar to other states of hypercortisolemia.
We analysed seventeen patients with septic postoperative spondylodiscitis (POD) who were managed by early microsurgical removal of the infected necrotic tissue, application of a closed ...suction-irrigation system (for a mean of 6.7 days), and early mobilisation. The POD was diagnosed clinically by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) values and radiographically by computerised tomography scanning or magnetic resonance imaging. According to the sensitivity studies of the obtained pathogens, systemic antibiotics were given, followed by early mobilisation of all patients in a light cast corset. Immediate pain relief was noted in all patients except one, who required a third operation that was followed by rapid clinical improvement. Bacteriological diagnosis was obtained in 88% of the patients. Excellent or good clinical long-term results were achieved in 82% of the patients, whereas 18% had poor results. Elevated ESR/CRP values returned to normal ranges within 6 to 44 days (mean 15 days) after reoperation. All but one patient tolerated early mobilisation (within 2 to 4 weeks) well without any complication. Early microsurgical removal of the necrotic and infected tissue and application of a closed suction-irrigation system supported by specific antibiotic therapy should be considered an effective means to treat POD, thereby avoiding a prolonged period of unpleasant immobilisation for the patient.
