Sleep oscillations related to memory consolidation during aromatases inhibitors for breast cancer.

Aromatase inhibitors (AIs) are associated with sleep difficulties in breast cancer (BC) patients. Sleep is known to favor memory consolidation through the occurrence of specific oscillations, i.e., slow waves (SW) and sleep spindles, allowing a dialogue between prefrontal cortex and the hippocampus. Interestingly, neuroimaging studies in BC patients have consistently shown structural and functional modifications in these two brain regions. With the aim to evaluate sleep oscillations related to memory consolidation during AIs, we collected polysomnography data in BC patients treated (AI+, n = 17) or not (AI-, n = 17) with AIs compared to healthy controls (HC, n = 21). None of the patients had received chemotherapy and radiotherapy was finished since at least 6 months, that limit the confounding effects of other treatments than AIs. Fast and slow spindles were detected during sleep stage 2 at centro-parietal and frontal electrodes respectively. SW were detected at frontal electrodes during stage 3. Here, we show lower frontal SW densities in AI + patients compared to HC. These results concord with previous reports about frontal cortical alterations in cancer following AIs administration. Moreover, AI + patients tended to have lower spindle density at C4 electrode. Regression analyses showed that, in both patient groups, spindle density at C4 electrode explained a large variance of memory performances. Slow spindle characteristics did not differ between groups and sleep oscillations characteristics of AI- patients did not differ significantly from those of both AI + patients and HC. Overall, our results add to the compelling evidence of the systemic effects of AIs previously reported in animals, with deleterious effects on cortical activity during sleep and associated memory consolidation in the current study. There is thus a need to further investigate sleep modifications during AIs administration. Longitudinal studies are needed to confirm these findings and investigation in other cancers on this topic should be conducted.

Sleep macro- and microstructure in breast cancer survivors.

Complaints of sleep disturbance are prevalent among breast cancer (BC) patients and are predictors of quality of life. Still, electrophysiological measures of sleep are missing in patients, which prevents from understanding the pathophysiological consequences of cancer and its past treatments. Using polysomnography, sleep can be investigated in terms of macro- (e.g. awakenings, sleep stages) and micro- (i.e. cortical activity) structure. We aimed to characterize sleep complaints, and macro- and microstructure in 33 BC survivors untreated by chemotherapy and that had finished radiotherapy since at least 6 months (i.e. out of the acute effects of radiotherapy) compared to 21 healthy controls (HC). Compared to HC, BC patients had a larger number of awakenings (p = 0.008); and lower Delta power (p < 0.001), related to sleep deepening and homeostasis; greater both Alpha (p = 0.002) and Beta power (p < 0.001), related to arousal during deep sleep; and lower Theta power (p = 0.004), related to emotion regulation during dream sleep. Here we show that patients have increased cortical activity related to arousal and lower activity related to sleep homeostasis compared to controls. These results give additional insights in sleep pathophysiology of BC survivors and suggest sleep homeostasis disruption in non-advanced stages of BC.

[Quantitative relationships between ADC and perfusion changes in acute ischemic stroke using combined diffusion-weighted imaging and perfusion MR (DWI/PMR)]. / Relation quantitative des modifications de la diffusion et de la perfusion au sein du parenchyme cerebral au cours de l'accident ischémique aigu.

UNLABELLED: MR-based diffusion- and perfusion-weighted imaging (DWI/PWI) has become the standard imaging technique to assess the individual brain pathophysiological status in acute ischemic stroke. The finding of a "mismatch" with larger PWI than DWI abnormality is thought to reflect the presence of tissue at-risk of infarction, i.e., penumbra. However, there has been no detailed study of the quantitative relationships between perfusion and diffusion changes in stroke patients. According to the experimental concept of penumbra, the ADC would be expected to remain unchanged despite decreasing perfusion until a critical threshold is reached. We have tested this hypothesis directly in man. METHODS: DWI/PWI was performed in 7 patients with MCA territory stroke within 4-10 hrs from onset. Mismatch was defined on diffusion and rMTT maps, and circular ROIs were positioned within the ADC lesion (D), the mismatch area (M), and the normal appearing cortex (N); mirror ROIs were also obtained, and affected/unaffected ratios for ADC and rCBF were computed for each ROI. RESULTS: The mean (+/-1 SD) ADC ratios were 0.60 +/- 0.09, 0.95 +/- 0.10 and 1.02 +/- 0.04 in L, M and N, respectively; the corresponding rCBF ratios were 0.32 +/- 0.12, 0.75 +/- 0.14 and 0.97 +/- 0.09, respectively. The relationship was non-linear, with the rCBF but not the ADC ratio for M being significantly lower (p < 0.01) than that for N. A threshold for decline in ADC was apparent around 0.50 rCBF ratio. COMMENT: These results directly document in man that the ADC declines only after hypoperfusion has reached a certain degree (about 50%), consistent with the concept of the ischaemic penumbra.

Concentration of bone elements in osteoporosis.

In aging and in osteoporosis, decreased bone density is associated with decreased bone mass. However, changes in the bone mineral phase remain a matter for investigation. In particular, it is unknown whether bone mineral loss is directly related to reduction in bone mass or associated with changes in the concentration of mineral elements in mineralized bone tissue. In this study, the cortical bone concentration of elements was determined in biopsies of the ilium from 33 subjects (12 controls and 21 individuals with untreated severe osteoporosis). Calcium and phosphorus concentrations were evaluated in cortical and trabecular bone using energy-dispersive x-ray (EDX) microanalysis and inductively coupled plasma optical emission spectrometry (ICPOES). Bone concentrations of Na, K, Mg, Cu, Zn, Fe, Sr, Al, B, and Si were also determined in cortical bone using ICPOES. Additionally, the concentration of F in cortical bone was measured with a specific ion electrode and the concentration of Pb was determined by atomic absorption spectrometry. In mineralized bone tissue there was no significant age-dependent variation in the concentration of Ca, P, or other elements either in controls or in osteoporotic subjects. Moreover, the concentration of elements in bone tissue did not differ in the two groups. These results suggest that the decrease in bone density in osteoporosis is directly related to evolution of the bone mass, without detectable changes in the concentration of elements in bone.

An ERD mapping study of the neurocognitive processes involved in the perceptual and semantic analysis of environmental sounds and words.

The aim of this paper was to investigate and compare the EEG mechanisms underlying the perceptual and semantic processes involved in environmental and language sounds perception by manipulating the degree of identification of sounds and using the ERD (event-related desynchronization) method in healthy subjects. Four types of stimuli were analyzed: meaningful environmental sounds, meaningless sounds, words and non-words. We report many similarities in the ERDs and ERSs (event-related synchronizations) patterns among all stimuli, with: (i) similar time-course of ERDs and ERSs between meaningful environmental sounds and words, and between meaningless sounds and non-words; (ii) similar topography of the maximal ERDs for meaningful environmental sounds, words and non-words; and (iii) same right posterior ERSs for all four stimuli. However, differences were also observed: (i) in time-course, with earlier ERSs for meaningless than meaningful stimuli, whether environmental or verbal; and (ii) in topography, with ERDs predominating in left and right hemisphere channels for meaningful and meaningless environmental sounds, respectively; (iii) ERSs predominating in the left temporal channel for non-words and in the left posterior and right frontal channels for meaningless sounds. The results of this study suggest that meaningful stimuli involve greater and longer-lasting semantic processes than meaningless stimuli, while the occurrence of ERSs for the latter points to the possible involvement of an inhibitory processing of semantic representations. Finally, the findings concerning the comparison between verbal and non verbal stimuli suggest the involvement of left-lateralized phonological and semantic processes for the former, and more distributed neurocognitive processes in both hemispheres for the latter although with predominant left laterality for their semantic processing.

Treatment of Paget's disease of bone with (4-chloro-phenyl) thiomethylene bisphosphonate.

Introduction of antiosteoclastic drugs, calcitonin and etidronate, has profoundly changed the treatment of active Paget's disease of bone. Nevertheless, the use of these drugs is limited in some patients by the occurrence of side-effects or by a resistance to therapy. We report the results of an open, nonrandomized study with a new bisphosphonate, (chloro-4 phenyl) thiomethylene bisphosphonate (Cl-TMBP), given orally to 35 patients with active Paget's disease of bone. At two different dosages this new bisphosphonate induced a significant decrease in disease activity. Patients receiving a mean dosage of 5 mg/kg/d (n = 14) showed a significant reduction of serum alkaline phosphatase levels to 43% of pretherapeutic values (from 499 +/- 91 to 214 +/- 41 IU/l) while hydroxyproline/creatinine ratio decreased to 43% of baseline (from 93 +/- 21 to 40 +/- 11). A second group of patients (n = 21) receiving a mean dosage of 11 mg/kg/d exhibited a similar response: serum alkaline phosphatase activity was reduced to 42% of initial values (from 1384 +/- 209 to 584 +/- 111 IU/l) while hydroxyproline/creatinine ratio fell to 48% of baseline (from 144 +/- 27 to 69 +/- 15). This was accompanied by a reduction in radionuclide uptake in pagetic areas. A prolonged beneficial effect was observed in most patients. In patients receiving the highest dosage significant reduction in serum calcium and rise in parathyroid hormone were observed. Otherwise no clinical or biological side-effect occurred throughout the study.

Aminohydroxypropylidene bisphosphonate (AHPrBP) treatment of severe immobilization hypercalcaemia in a young patient.

We report a case of severe hypercalcaemia in a 16-year-old patient, 24 weeks after immobilization for quadriplegia. The biochemical and histomorphometric parameters showed increased osteoclastic resorption and decreased osteoblastic formation. Hydration, chair sitting, salmon and porcine calcitonin, sodium etidronate were unable to normalize the hypercalcaemia. The new antiosteoclastic agent, 3-amino-1 hydroxypropylidene-1, 1-bisphosphonate (AHPrBP), was effective in normalizing serum calcium and biochemical parameters of osteoclastic activity within five days. Bone histomorphometry showed a marked reduction in osteoclastic activity after AHPrBP treatment, as well as a drastic depression of osteoblastic activity, presumably due to the reduction of bone turnover. This case represents to our knowledge, the first successful use of AHPrBP in the treatment of immobilization hypercalcaemia.

A new method for quantifying EEG event-related desynchronization:amplitude envelope analysis.

Amplitude modulation (AM) analysis defines precisely the EEG signal envelope changes at sampling frequency. Here we demonstrate mathematically that event-related desynchronization (ERD) corresponds to the integration of AM-EEG. We applied this new approach to a group of 12 healthy human volunteers hearing repeated auditory stimuli and statistically compared the results from ERD to those from AM-EEG. The results indicate that AM-EEG characterized more precisely a specific evoked EEG cortical activation event and may be a powerful method for studying the time-course of functional dynamic brain EEG mapping with improved time resolution.

High temporal resolution dynamic mapping of instantaneous EEG amplitude modulation after tone-burst auditory stimulation.

A new method of instantaneous EEG analysis based on amplitude modulation (AM-EEG) was applied to analyze the AM-EEG changes in the alpha frequency band (8.20-12.89 Hz) for successive 5 ms epochs. Repeated auditory tone-burst stimuli (of 220 ms duration) were presented at fixed 2.56 second intervals to 12 attending right-handed young female volunteers, who were EEG-recorded over 19 EEG channels at 200 Hz sampling frequency. The time-course of functional activation was characterized in terms of percent decrease in instantaneous amplitude modulation, as compared to baseline, in analogy with the classical event-related desynchronization paradigm. A dynamic sequence of the successive 122 AM-EEG maps obtained for the 610 ms from beginning of tone-burst was stored and later animated on PC microcomputer. Topological changes among successive maps were extracted into 40 specific AM-EEG maps. Early left temporal and centro-temporal activation was observed, followed first by strong bilateral frontal, and then by left temporal activation. These changes induced by a warning tone-burst are discussed in terms of functional neurophysiology. The present method therefore allows an improved time-resolution for functional brain activation paradigms.

Effect of environmental sound familiarity on dynamic neural activation/inhibition patterns: an ERD mapping study.

The aim of this study was to analyze the timing and topography of brain activity in relation to the cognitive processing of different types of auditory information. We specifically investigated the effects of familiarity on environmental sound identification, an issue which has been little studied with respect to cognitive processes, neural substrates, and time course of brain activity. To address this issue, we implemented and applied an electroencephalographic mapping method named event-related desynchronization, which allows one to assess the dynamics of neuronal activity with high temporal resolution (here, 125 ms); we used 19 recording electrodes with standard positioning. We designed an activation paradigm in which healthy subjects were asked to discriminate binaurally heard sounds belonging to one of two distinct categories, "familiar" (i.e., natural environmental sounds) or "unfamiliar" (i.e., altered environmental sounds). The sounds were selected according to strict preexperimental tests so that the former should engage greater semantic, and the latter greater structural, analysis, which we predicted to preferentially implicate left posterior and right brain regions, respectively. During the stimulations, significant desynchronizations (thought to reflect neuronal activations) were recorded over left hemisphere regions for familiar sounds and right temporofrontal regions for unfamiliar sounds, but with only few significant differences between the two sound categories and a common bilateral activation in the frontal regions. However, strongly significant differences between familiar and unfamiliar sounds occurred near the end of and following the stimulations, due to synchronizations (though to reflect deactivations) which appeared over the left posterior regions, as well as the vertex and bilateral frontal cortex, only after unfamiliar sounds. These unexpected synchronizations after the unfamiliar stimuli may reflect an awareness of the unfamiliarity of such sounds, which may have induced an inhibition of semantic and episodic representations because the latter could not be associated with meaningless sounds.

[Study of bone repercussion in 33 cases with anorexia nervosa which 8 with fracture osteoporosis]. / Etude du retentissement osseux dans 33 cas d'anorexie mentale dont 8 avec une osteoporose fracturaire.

A national survey has regrouped 33 cases of anorexia nervosa (AN) with osseous investigations, in particular an absorptiometry of the lumbar spine. 2 groups have been defined: 25 patients without fracture (F-) and 8 patients with osteoporotic fractures (F+), including 5 cases with 12 vertebral fractures and 5 with non vertebral fractures: 31/33 have a low lumbar bone mineral content (BMC). The lumbar BMC of the F+ is significantly lower than the F-: -4.1 +/- 1.6 DS versus -2.2 +/- 1.2 DS (p less than 0.001). 5 F+ patients are under the fracture threshold (FT), (O F-), 2 F+ are on the same level as the FT, and the last F+ has a lumbar BMC 15% above the FT, but an osteoporotic wrist fracture and a very low femoral neck BMC (0.64 g/m2, normal 1.06 +/- 0.15). F+ are older (35.2 year old versus 23.6, p less than 0.001), owing the fact that the duration of the AN (+ 9.2 years, p less than 0.005) and of the amenorrhea (+ 9.8 years, p less than 0.001) are longer, although the AN began at the same age in the 2 groups. The minimum weight, the body mass index, the percentage of loss of weight are similar in the 2 groups. Phosphocalcic biological studies, which show rather high osteocalcinemia and hydroxyprolinuria (hyperremodeling), with rather high serum 1-25 OH vitamin D, do not differ between the 2 groups. Endocrinologic evaluations, with a constant hypooestradiolemia of hypothalamic origin, low somatomedinemia and normal cortisolemia, are not different between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)