[Prostate cancer of elderly patients: Place and role of geriatric assessment]. / Cancer de prostate des sujets âgés : place et rôle de l'évaluation gériatrique.

INTRODUCTION: The aim of this study was to appreciate the place and role of geriatric assessment in elderly patients with prostate cancer. MATERIALS AND METHODS: We performed a retrospective analysis of prostate cancer patients who underwent geriatric assessment during the therapeutic management from 2008 to 2014. Patient, tumor, treatment characteristics and their associated toxicity as well as the parameters of geriatric assessment were studied. The occurrence of geriatric assessment within the 3 months preceding a therapeutic decision was reviewed. RESULTS: Data of seventy-four patients were analyzed with a median follow-up of 15.6 years. The average age at diagnosis was 74.3 and 80.6 at the geriatric assessment. At the time of the geriatric assessment 64 patients had metastatic disease, 39 were in poor condition more than 50% of patients had walking ability disorders. Thirteen patients underwent radical surgery, 28 received radiotherapy, 30 patients had chemotherapy and hormonotherapy was prescribed for 72 patients. The geriatric assessment, requested on average 15 years after diagnosis, was not carried out within the 3 months preceding treatment decision for 55 patients. CONCLUSION: The recourse to geriatric assessment is predominantly used to endorse a decision of supportive care for elderly patients with prostate cancer. An early intervention by a geriatrician consultant for the initial management and then at each therapeutic event is a sine qua non condition for efficient personalized therapeutic management suitable to every patient according to physiological age. LEVEL OF EVIDENCE: 4.

[Diagnosing pulmonary embolism during pregnancy: how should we do?]. / Diagnostic de l'embolie pulmonaire chez la femme enceinte: comment faire?

No diagnostic strategy for pulmonary embo- lism (PE) during pregnancy is based on strong evidence and unanimously accepted. Clinical scores are not validated. The diagnostic yield of the non radiating tests is low: D-dimer is rarely negative in pregnant women and lower limb venous compression ultrasonography is poorly sensitive. Nevertheless, they are still recommended as first line exams. The radia- ting exams (ventilation-perfusion scintigra- phy and thoracic angio-CT) have an equiva- lent diagnostic yield (more than 90%). But both raise the risk of cancer: any childhood cancer for the fetus (scintigraphy), and breast cancer for the mother (angio-CT). However, the diagnosis of PE in the pregnant woman has a major impact and must be established with certainty, even if this requires performing radiation imaging.

Peripheral chemosensitivity and central integration: neuroplasticity of catecholaminergic cells under hypoxia.

The plasticity of catecholaminergic cells within the carotid body, brainstem and sympatho-adrenal system was analyzed in rats subjected to normobaric hypoxia (10% O2) lasting up to 3 weeks. Long-term hypoxia elicited structural, neurochemical and phenotypic changes in carotid body and sympathetic ganglia (SIF cells), and stimulated the norepinephrine turnover in A2 neurons located caudal to the obex, the area where the chemosensory nerve fibers end. Chemodenervation abolished central alterations. Adaptive mechanisms for increasing norepinephrine biosynthesis in hypoxia involved changes in activity of pre-existing tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis, and induction of new tyrosine hydroxylase protein. These neurochemical changes occurred after sustained hypoxia only, suggesting that noradrenergic neurons are involved in the central chemoreceptor pathway during sustained hypoxia but are not essential for regulatory responses to acute hypoxia. Acute hypoxia elicited the expression of c-Fos protein in neurons located in nucleus tractus solitarius that were not catecholaminergic. Noradrenaline released under long-term hypoxia could play a neuromodulatory role in ventilatory acclimatization. Cardiovascular responses to hypoxia are mediated by changes in sympatho-adrenal outflow, different according to the target organ. Cardiac sympathetic output and adrenal secretion were stimulated independently of carotid body chemoafferents. Early postnatal hypoxia induced long-term neurochemical changes in carotid body, brainstem and sympathetic efferents that may reveal alterations in development of neurons involved in the chemoreceptor pathway.

Reward dependence is positively related to urinary monoamines in normal men.

According to Cloninger, three major personality dimensions, novelty seeking, harm avoidance, and reward dependence, are dependent on central monoaminergic systems. This study examined the relationship between the urinary levels of different monoamines and the above personality dimensions. Fifty normal men answered the Tridimensional Personality Questionnaire (TPQ); their levels of dopamine, norepinephrine, epinephrine, normetanephrine, metanephrine, 3-methoxy-4-hydroxyphenylglycol, vanilmandelic acid, homovanilic acid, and serotonin metabolite 5-hydroxyindolacetic acid were measured in urine on two consecutive nights. Significant and positive correlations were found between reward dependence, 3-methoxy-4-hydroxyphenylglycol, and epinephrine (r = .50 and r = .51, respectively). Monoamine levels explained 44% of the variance of reward dependence. Cluster analysis identified three groups of subjects presenting specific patterns of monoamine excretion. The TPQ scores could discriminate among subjects belonging to these clusters. These results point out a narrow relationship between urinary monoamine excretion and the basic personality dimension of reward dependence.

Long-term impairment in the neurochemical activity of the sympathoadrenal system after neonatal hypoxia in the rat.

The study evaluates the long-term effect of neonatal hypoxia on the neurochemical activity of the sympathoadrenal system in the rat. One-day-old male pups were exposed to hypoxia (10% O2) for 6 d and thereafter reared under normoxia. Neonatal hypoxia reduced the body weight of 3- and 8-wk-old rats and did not change the blood pressure at 6 wk of age. In sympathetic ganglia, the content and/or turnover rates of norepinephrine were reduced in neonatal-hypoxic rats of 3 and 8 wk of age, but the content and turnover rates of dopamine were unaltered. The effect was not dependent on the type of ganglion. In the superior cervical ganglion, neonatal hypoxia had a selective effect on the type of catecholamine (dopamine versus norepinephrine), thus suggesting a selective-altered maturation of noradrenergic neurons, but presumably not of the dopaminergic small, intensely fluorescent cells. A long-term deficiency in adrenal activity was the consequence of neonatal hypoxia, as shown by the decrease in the content and turnover rate of dopamine. Neonatal hypoxia elicited a long-term decrease in the content and turnover rates of norepinephrine in heart and lungs but failed to induce a significant effect in kidneys. However, this effect was not tissue-specific. Data provide evidence that a hypoxic episode occurring during a critical period of development in the rat induces a long lasting decrease in the neurochemical activity of the sympathoadrenal system. These results are discussed in terms of their implications for human pathology.

Long-term influence of neonatal hypoxia on catecholamine activity in carotid bodies and brainstem cell groups of the rat.

1. In order to determine the long-term influence of neonatal hypoxia on catecholaminergic activity in peripheral arterial chemoreceptors and brainstem noradrenergic cell groups (A1, A2, A5 and A6), 1-day-old male rat pups were subjected to hypoxia (10% oxygen) for 6 days and then supplied with normal air. Control animals were kept at normoxia from birth. Rats were killed at either 3 or 8 weeks of age. 2. The content of dopamine and noradrenaline in carotid bodies of neonatally hypoxic rats was increased at both 3 and 8 weeks of age. 3. Noradrenaline turnover was selectively decreased in the caudal portion of A2 (located in the area of chemosensory afferent projection) at 8 weeks of age (-76 +/- 2%), while this turnover was unaffected in rostral A2 cells. Noradrenergic activity in A1, A5 and A6 was altered by neonatal hypoxia in an age-dependent fashion. 4. The data suggest that neonatal hypoxia induces long-term changes in the basal activity of the carotid body and brainstem noradrenergic cell groups. Such changes might contribute to neuronal regulation of the delayed respiratory, arousal and neural sequelae associated with neonatal hypoxia. These changes could also be involved in the early programming of respiratory and blood pressure control.

Lower sex hormones in men during anticipatory stress.

Free cortisol, luteinizing hormone (LH), total testosterone and monoamines were measured in two successive nocturnal urine collections in 50 healthy men to assess the influence of anticipatory stress. The first collection (N-2) was two nights before and the second (N-1) was just on the night before a one-day experimental stressor consisting of participation in a one-day clinical research protocol. The mean cortisol level increased from 23.4 (N-2) to 66.6 micrograms (N-1), while mean LH level decreased from 2.68 (N-2) to 1.71 IU (N-1) and the mean testosterone level fell from 1.31 (N-2) to 0.70 microgram (N-1). There were no changes in monoamines. Inhibition of sex hormones is a relatively neglected area of stress research.

Delayed increase of tyrosine hydroxylation in the rat A2 medullary neurons upon long-term hypoxia.

In vivo and in vitro activity of tyrosine hydroxylase (TH) was estimated in the catecholaminergic A2 cell group of the nucleus tractus solitarius (NTS) in rats exposed to normobaric hypoxia (10% O2 in nitrogen) for 2 h, 3, 7, 14 or 21 days. The A2 cell group was subdivided into two subgroups. In the caudal A2 subgroup located caudal to the calamus scriptorius, long-term but not acute hypoxia elicited an increase of in vivo tyrosine hydroxylation rate after 7 days of exposure (+60% above normoxic controls). The increase of in vivo TH activity was maintained at the same level at the end of hypoxic exposure. In vitro TH activity was increased transiently after 7 days of hypoxia (+92% above normoxic (controls). In thr rostral A2 subgroup, hypoxia elicited a significant increase of in vivo tyrosine hydroxylation at 7 days (+38%) but did not alter in vitro TH activity throughout the whole exposure. Hypoxia produced no detectable change in TH activity in other noradrenergic cell groups of the brain stem (locus coeruleus, A5) except for a transient inhibition of in vivo TH activity in A5 after 2 h. Immunocytochemical analyses confirmed that the catecholaminergic neurons in the caudal A2 area are not only of a noradrenergic nature. The neurons were located in the commissural subnucleus of the NTS. On the other hand, the rostral A2 area contains noradrenergic neurons intermingled with a small number of adrenergic cell bodies.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ecoepidemiology of Lyme borreliosis in the Rhône-Alps region. Distribution, ecological context, relationship to the distribution of Ixodes ricinus (Linnaeus, 1758)]. / Ecoépidémiologie de la borréliose de Lyme dans la région Rhône-Alpes. Répartition, contexte écologique, relations avec la distribution d'Ixodes ricinus (Linné, 1758).

The aim of the study was to precise the geographical repartition of Lyme borreliosis in the Rhône-Alpes district, to describe the ecological characteristics of the areas propitious to the disease, and to verify the vectorial competence of I. ricinus. The cases of Lyme disease were located by means of a questionnaire sent to 1156 physicians. The vector role of I. ricinus was studied by two ways: firstly by searching a correlation between the geographical repartition of the tick and that of cases, secondly by proving the Borrelia infection of the tick. Lyme disease is widely spread in the study area, mainly at the foothill level, its repartition is largely coinciding with that of I. ricinus which was found infected by B. burgdorferi (s.l.). However a few cases, located near the Mediterranean area, set an unanswered problem.

Ventilatory acclimatization to chronic hypoxia: relationship to noradrenaline metabolism in the rat solitary complex.

1. The relationship between ventilatory acclimatization to chronic hypoxia (10% O2-90% N2) and noradrenaline metabolism was examined in two regions located immediately caudal and rostral to the obex within the rat solitary complex. 2. Three experimental protocols were established. In protocol 1, the percentage changes in respiratory tidal volume, frequency and minute ventilation elicited by 4, 7, 10 and 14 days of hypoxia were assessed by flow plethysmography in awake rats, and then the content of tyrosine hydroxylase was measured in the solitary complex. In protocol 2, the time course response of tyrosine hydroxylase protein level was determined after 3, 7, 14 and 22 days of hypoxia by using a quantitative immunoblotting method for the protein assay. In protocol 3, the turnover of noradrenaline was estimated in the solitary complex after 14 days of hypoxia. 3. A progressive increase in ventilation was observed to reach a maximum (+105 +/- 15%, mean +/- S.E.M.) above normoxic control after 10 days of hypoxia, at which time it stabilized. Furthermore, tyrosine hydroxylase protein increased progressively and reached a maximal level at 14 days of hypoxia (+36 +/- 4%, mean +/- S.E.M.). Return to the basal level of tyrosine hydroxylase was observed after 22 days of hypoxia. 4. Tyrosine hydroxylase content (+36 +/- 4%) and noradrenaline turnover (+394 +/- 3%) increased exclusively in the caudal part of the solitary complex. 5. The ventilatory acclimatization to chronic hypoxia preceded the increase in tyrosine hydroxylase and these two parameters were significantly correlated. 6. These data suggest that ventilatory acclimatization to chronic hypoxia is associated with topical modifications of the brainstem catecholamine metabolism.

Differential effects of long-term hypoxia on norepinephrine turnover in brain stem cell groups.

The influence of long-term hypoxia on noradrenergic cell groups in the brain stem was assessed by estimating the changes in norepinephrine (NE) turnover in A1, A2 (subdivided into anterior and posterior parts), A5, and A6 groups in rats exposed to hypoxia (10% O2-90% N2) for 14 days. The NE turnover was decreased in A5 and A6 groups but failed to change significantly in A1. The NE turnover was increased in the posterior part of A2 and remained unaltered in the anterior part. In normoxic rats, the hypotensive drug dihydralazine induced a reverse effect, namely increased NE turnover in anterior A2 and no change in posterior A2. The neurochemical responses to hypoxia were abolished by transection of carotid sinus nerves. The results show that long-term hypoxia exerts differential effects on the noradrenergic cell groups located in the brain stem. Peripheral chemosensory inputs control the hypoxia-induced noradrenergic alterations. The A2 cell group displays a functional subdivision: the posterior part is influenced by peripheral chemosensory inputs, whereas the anterior part may be concerned with barosensitivity.

Influence of long-term hypoxia on tyrosine hydroxylase in the rat carotid body and adrenal gland.

Tyrosine hydroxylase (TH) protein was measured in the carotid body and adrenal gland of rats exposed to normobaric hypoxia (10% O2 in nitrogen) for 3, 7, 14 or 22 days. After 22 days of hypoxia, a gradual increase in TH protein content was observed in the carotid body and in the adrenal gland, reaching 168% and 148% of the normoxic controls, respectively. To determine if the increase in TH protein content in the carotid body could alter catecholamine biosynthesis, in vitro TH activity and catecholamine turnover were measured in rats submitted to hypoxia for 14 days. TH activity was increased by 11.2-fold, while the turnover of dopamine and norepinephrine was increased by 14.8- and 5.4-fold, respectively. The data show that long-term hypoxia exerts a stimulatory influence on TH protein in the carotid body and adrenal gland in addition to an elevation in dopamine and norepinephrine biosynthesis in the carotid body.