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Biomedical subjects

A Lacroix

Publications and source records attributed to A Lacroix.

At least 37 records · Page 2Linked to original sources

Phagocytic response of macrophages from the pronephros of American plaice (Hipoglossoides platessoides) exposed to contaminated sediments from Baie des Anglais, Quebec.

Sediments of Baie des Anglais on the St. Lawrence estuary have a history of environmental contamination, but little information exists regarding their toxicity. The purpose of the present study was to determine the effects of contaminated Baie des Anglais sediments on American plaice (Hippoglossoides platessoides) immune function. Three sites in Baie des Anglais were selected which vary in proximity to local industries and in their sediment contaminant load. Sites 1 and 2 (within the bay) are the closest to shore and most heavily contaminated while sediments at Site 3, which is outside the bay, are the least contaminated. In the first experiment, American plaice were placed in cages at each site for three weeks and immune function was assessed by measuring the phagocytic activity of pronephric macrophages. At the time of sampling, plaice displayed pronephros cell immune response disturbances indicating that Site 1 and 2 were most toxic and Site 3 the least toxic. The results obtained for phagocytosis revealed that contaminants present in the sediments are bioavailable to fish, which came in contact with them and significantly affected their immune system. In the second experiment, sediments from the most toxic site, Site 1, were collected for a laboratory controlled experiment in which plaice were exposed for up to 3 months to these contaminated marine sediments, while the control group was exposed to relatively uncontaminated beach sand. At the end of the exposure period, plaice were transferred from contaminated sediment to beach sand and sampled one month later in order to determine if immune function had returned to control levels. The total number of macrophages decreased following three months of exposure, while the active macrophages had already decreased after the first month of exposure. Following the rehabilitation period a significant trend toward normal response was noted. Sediments from Baie des Anglais contain primarily less highly chlorinated PCBs and lower concentrations of the intermediate and highly chlorinated PCBs. The total concentration of PCBs (sum of 20 congeners) in the contaminated sediments was 1500 ng/g while in the beach sand, the levels were 13.6 ng/g dry weight. Only the low chlorinated PCB congeners were efficiently transferred from the sediments to the plaice liver. Together, these results suggest that the effect of chemical exposure on the phagocytosis of plaice macrophages may be reversible if the fish are returned to a non-contaminated habitat.

Adaptation, Physiological↗

Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome.

The mechanism by which cortisol is produced in adrenal Cushing's syndrome, when ACTH is suppressed, was previously unknown and was referred to as being "autonomous." More recently, several investigators have shown that some cortisol and other steroid-producing adrenal tumors or hyperplasias are under the control of ectopic (or aberrant, illicit, inappropriate) membrane hormone receptors. These include ectopic receptors for gastric inhibitory polypeptide (GIP), beta-adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT4), or possibly leptin. The presence of aberrant receptors places adrenal cells under stimulation by a trophic factor not negatively regulated by glucocorticoids, leading to increased steroidogenesis and possibly to the proliferative phenotype. The molecular mechanisms responsible for the abnormal expression and function of membrane hormone receptors are still largely unknown. Identification of the presence of these illicit receptors can eventually lead to new pharmacological therapies as alternatives to adrenalectomy, now demonstrated by the long-term control of ectopic P-AR- and LH/hCGR-dependent Cushing's syndrome by propanolol and leuprolide acetate. Further studies will potentially identify a larger diversity of hormone receptors capable of coupling to G proteins, adenylyl cyclase, and steroidogenesis in functional adrenal tumors and probably in other endocrine and nonendocrine tumors.

Adrenal Gland Diseases↗

Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome.

Cortisol secretion in adrenal Cushing's syndrome can be regulated by the aberrant adrenal expression of receptors for gastric inhibitory polypeptide, vasopressin, catecholamines, LH/human CG (LH/hCG), or serotonin. Four patients with incidentally discovered bilateral macronodular adrenal hyperplasia without clinical Cushing's syndrome were evaluated for the possible presence of aberrant adrenocortical hormone receptors. Urinary free cortisol levels were within normal limits, but plasma cortisol levels were slightly elevated at nighttime and suppressed incompletely after dexamethasone administration. Plasma ACTH was partially suppressed basally but increased after administration of ovine CRH. A 51-yr-old woman had ACTH-independent increases of plasma cortisol after 10 IU AVP im (292%), 100 microg GnRH iv (184%), or 10 mg cisapride orally (310%); cortisol also increased after administration of NaCl (3%), hCG, human LH, and metoclopramide. In a 61-yr-old man, cortisol was increased by AVP (349%), GnRH (155%), hCG (252%), and metoclopramide (191%). Another 53-yr-old male increased plasma cortisol after AVP (171%) and cisapride (142%). Cortisol secretion was also stimulated by vasopressin in a 54-yr-old female. This study demonstrates that subclinical secretion of cortisol can be regulated via the aberrant function of at least V1-vasopressin, LH/hCG, or 5-HT4 receptors in incidentally identified bilateral macronodular adrenal hyperplasia.

Adrenal Hyperplasia, Congenital↗

[Illicit hormone receptors in adrenal Cushing's syndrome].

Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenomas or bilateral macronodular adrenal hyperplasia; this syndrome results from the adrenal overexpression of the GIP receptor, which was found to be without an activating mutation. An increased stimulation of cortisol secretion following administration of vasopressin was also reported by several investigators in patients with adrenal Cushing's syndrome; this was linked to an increased expression or abnormal response of the V1-vasopressin receptor. We have conducted a prospective in vivo evaluation of 20 patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In 6 cases of macronodular adrenal hyperplasia, we have identified, in addition to 2 cases of GIP-dependent Cushing's syndrome, 4 other patients in whom cortisol production was regulated abnormally either by vasopressin, B-adrenergic receptor agonists, hCG/LH, or serotonin 5-HT-4 receptor agonists. In 13 patients with unilateral adrenal adenoma, an abnormal response to a mixed meal or to vasopressin was found in 3 cases, suggesting that the presence of ectopic or abnormal hormone receptors is less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists of the abnormal receptors.

Adenoma↗

Recovery of the brain choline level in treated Cushing's patients as monitored by proton magnetic resonance spectroscopy.

In a previous study from our group [A. Khiat, C. Bard, A. Lacroix, J. Rousseau, Y. Boulanger, Brain metabolic alterations in Cushing's syndrome as monitored by proton magnetic resonance spectroscopy, NMR Biomed. 12 (1999) 357-363], proton magnetic resonance spectroscopy (1H MRS) was used to evaluate changes in cerebral metabolites in patients with Cushing's syndrome as compared to normal subjects. Data recorded in the frontal, thalamic and temporal areas demonstrated statistically significant decreases of the Cho/Cr ratios in the frontal and thalamic areas but not in the temporal area for Cushing's syndrome patients. No statistically significant changes in the NAA/Cr ratios were measured in any of the areas studied. In this follow-up study, MRS data are reported for ten patients after correction of hypercortisolism which demonstrate a statistically significant recovery of the choline levels in the frontal and thalamic areas. No variation in the NAA, Cr and mI metabolite ratios relative to H(2)O could be measured. Results are interpreted as an inhibition of the phosphatidylcholine degrading phospholipases by glucocorticoids which disappears after correction of hypercortisolism.

Adult↗

Reproductive endocrinology of tropical seabirds: sex-specific patterns in LH, steroids, and prolactin secretion in relation to parental care.

Plasma levels of luteinizing hormone, prolactin, testosterone, and progesterone were measured throughout breeding in masked boobies, red-footed boobies, and red-tailed tropicbirds at Europa and Tromelin Islands (Indian Ocean). LH secretion showed a dampened pattern in the three species, particularly in tropicbirds. Such specific differences may be related to the less elaborate courtship displays in tropicbirds. Testosterone levels were very low throughout breeding in all three species, particularly in boobies. Low testosterone values in boobies may be related to their year-round attendance at the colony. Prolactin secretion increased from the prelaying period until the incubation and brooding periods and declined thereafter in boobies but stayed relatively unchanged throughout the breeding cycle in tropicbirds. The relatively constant prolactin secretion in the more pelagic tropicbirds might allow them to undertake parental care despite long absences at sea. Boobies perform postfledging care with basal prolactin levels. For all species, females always have higher prolactin levels than males. This hormonal dimorphism, being more pronounced in boobies, may be associated with differences in parental care between mates.

Animals↗

Progesterone inhibits female courtship behavior in domestic canaries (Serinus canaria).

We studied copulation solicitation display (CSD) responses to playback in photostimulated female canaries given systemic injections of progesterone. Eight females received injections of 0.1 mg of progesterone dissolved in olive oil during their first breeding cycle and were untreated during their second breeding cycle; eight females received only the oil vehicle during their first breeding cycle and received no treatment during their second breeding cycle. The injections were performed every second day during 15 days, after the onset of nest building. Progesterone treatment resulted in a significant increase of plasma progesterone which in turn provoked an inhibition of females' CSDs and decreased the size of the clutch. During the first breeding cycle, progesterone-treated females had lower CSDs and egg-laying scores than did control females. During the second breeding cycle, when females received no treatment, no differences emerged between the two groups. The suppressive effect of progesterone on female sexual responses was observed as soon as 48 h after the beginning of the treatment. We propose that progesterone plays a key role in mediating the transition from active female courtship behavior to sexual refractoriness in this species. Suppressive effects of progesterone on female sexual behavior have been previously described in lizards as well as in rodents. Our data are consistent with the hypothesis of Godwin et al. (J. Godwin, V. Hartman, M. Grammer, and D. Crews, Horm. Behav. 30, 138-144, 1996) which proposed that the decrease in sexual behavior following plasma progesterone increase represents an evolutionarily conserved mechanism in the regulation of female sexual behavior.

Animals↗

Cognitive decline in patients with Cushing's syndrome.

Chronic exposure to elevated glucocorticoid levels in Cushing's syndrome (CS), is associated with deficits in cognitive function and in emotion. The hippocampus plays a crucial role in the behavioral manifestations of the syndrome as it is richest in glucocorticoid receptors and is thus particularly vulnerable to glucocorticoid excess. The wide distribution of glucocorticoid receptors throughout the cerebral cortex, however, suggests that several cognitive functions can also be affected by the dysregulation of glucocorticoids. In this study, we investigated how an excess of glucocorticoid hormones affects cognitive processes. Nineteen patients with chronic hypercortisolemia due to CS were compared to healthy controls matched for age, sex, education, and occupation in tests of processing of visual and spatial information, memory, reasoning and concept formation, language and verbal functions, and attention. Multivariate and univariate analyses revealed overall differences in tests of treatment of visual and spatial information, reasoning and concept formation as well as in verbal and language performance, with poorer performance from CS patients. Differences were also observed in nonverbal aspects of memory and in attention tasks. The results suggest that chronic exposure to elevated levels of cortisol is associated with deficits in several areas of cognition, particularly those involving processing of selective attention and visual components. This study also shows that hormones play an important role in the modulation of cognitive function and that their influence on cerebral structure and function merits closer scrutiny.

Adult↗

GIP-dependent adrenal Cushing's syndrome with incomplete suppression of ACTH.

ACTH-independent Cushing's syndrome may be due to the development of ectopic hormone receptors in adrenal tissue. Thus, in food-dependent Cushing's syndrome the adrenals aberrantly express receptors for gastric inhibitory polypeptide (GIP). We present the case of a 60-year-old woman with food-dependent Cushing's syndrome whose cortisol levels increased after stimulation with CRH. In this patient with Cushing's syndrome the finding of low basal plasma cortisol levels in the late night and early morning as well as a paradoxical rise of plasma cortisol during a 7-h infusion with dexamethasone (carried out without any restriction in food intake), suggested that cortisol production was stimulated at times of food intake. Hourly measurements of plasma cortisol for 48 h revealed prominent meal-related peaks. A plasma cortisol response, elicited by oral glucose administration, could be prevented by octreotide. Plasma ACTH was low or undetectable. CRH administration was followed by a ACTH response from 3 to 16 ng/l and a plasma cortisol response from 230 to 680 nmol/l. Octreotide treatment for nearly five months induced a partial clinical and biochemical remission. Total bilateral adrenalectomy was performed. The left adrenal was grossly enlarged (7 x 5.5 x 4 cm) and the right adrenal was slightly enlarged (6 x 4 x 1.8 cm). Microscopy revealed bilateral nodular hyperplasia. Cell suspensions of adrenal tissue from the patient did respond in a dose-dependent fashion to stimulation with GIP and were very sensitive to stimulation with synthetic ACTH1-24. However, CRH had no significant effect on cortisol production in vitro. Using RT-PCR amplification and cDNA hybridization, GIP receptor was found to be overexpressed in the left and right adrenal tissues from this patient as compared to adrenal tissues from a normal individual or from non GIP-dependent adrenal Cushing's syndrome. There was no evidence of presence of adrenal CRH receptors. Thus, in this patient with food-dependent Cushing's syndrome, the CRH-induced plasma ACTH and cortisol response is probably mediated by an incomplete suppression of the HPA axis as a result of the intermittent food-dependent nature of Cushing's syndrome.

Adrenal Cortex↗

Are ectopic or abnormal membrane hormone receptors frequently present in adrenal Cushing's syndrome?

Twenty consecutive patients with adrenal Cushing's syndrome were studied with an in vivo protocol to determine the prevalence and diversity of the presence of ectopic or abnormal hormone receptors in their adrenal tissues. All six patients with bilateral ACTH-independent macronodular adrenal hyperplasia were found to have one or two abnormal adrenal receptors, including those for gastric inhibitory polypeptide, vasopressin (V1-vasopressin), beta-adrenergic agonists, LH/human CG, or serotonin 5-HT4. The presence of abnormal hormone receptors was found to be less frequently present in unilateral adenomas or carcinomas (3 of 14). The identification of abnormal adrenal hormone receptors can allow new pharmacological therapies of hypercortisolism. We suggest that the clinical screening for the presence of abnormal hormone receptors should be conducted in patients with adrenal Cushing's syndrome and, more particularly, in those with ACTH-independent macronodular adrenal hyperplasia, in the hope of offering medical therapy as an alternative to bilateral adrenalectomy.

Adenoma↗

The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies.

Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ss-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

Adrenocorticotropic Hormone↗

A case-control study of toenail selenium and cancer of the breast, colon, and prostate.

To study the possible role of dietary and supplementary selenium intake in the etiology of cancer, we carried out a case-control study of breast, colon, and prostate cancer in Montreal between 1989 and 1993. In this study, we were able to interview a total of 1,048 incidence cases of colon (402), breast (414) and prostate (232) cancer subjects and 688 population-based controls matched for age and gender. Of these, a total of 501 cancer cases and 202 controls produced toenail samples for their selenium concentrations, which were determined by neutron activation analysis. We found no association between toenail selenium and breast cancer (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.4-1.31) or prostate cancer (OR, 1.14; 95% CI, 0.46-2.83), though we did observe a statistically significant inverse association between toenail selenium level and the risk of colon cancer for both genders combined (OR, 0.42; 95% CI, 0.19-0.93; P = .009) and for female subjects (P = .050). We also found that nonsmoker case and control subjects had higher selenium in their toenail samples. This could be due either to the nature of tobacco, which reduces selenium absorption, or to smokers' consumption of certain foods containing less selenium. Further epidemiologic studies are required to clarify the role of selenium in the etiology of certain cancers.

Adolescent↗

Proteolytic degradation of hemoglobin by endogenous lysosomal proteases gives rise to bioactive peptides: hemorphins.

Hemorphin generation by mice peritoneal macrophages has been recently reported, nevertheless no conclusive data exist to localize clearly the macrophage proteolytic activity implicated in their generation. Because lysosomes are believed to be the main site of degradation in the endocytic pathway, we have studied their potential implication in the generation of hemorphins from hemoglobin. When this protein is submitted to purified rat liver lysosomes, an early generation of hemorphin-7-related peptides, detected by a radioimmunoassay, was observed. These peptides seemed to be relatively stable during the first hours of hydrolysis.

Animals↗

Brain metabolic alterations in Cushing's syndrome as monitored by proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy ((1)H MRS) was used to evaluate changes in cerebral metabolites in 13 patients with Cushing's syndrome (including seven with pituitary corticotroph adenomas and six with primary adrenal disease) as compared to 40 normal subjects. Data were recorded in the frontal, thalamic and temporal areas; quantification of the MRS signals demonstrated a statistically significant decrease of the Cho/Cr ratio in the frontal and thalamic areas but not in the temporal area for patients with Cushing's syndrome. The largest decrease in Cho/Cr was measured in the thalamic area of patients with a Cushing's syndrome secondary to an adrenal disease. No statistically significant changes in the NAA/Cr ratio were measured in any of the areas studied. These results suggest that the quantification of choline levels could be helpful for monitoring the cerebral metabolite alterations in patients with hypercortisolism.

Adult↗

Asynchronous development of bilateral nodular adrenal hyperplasia in gastric inhibitory polypeptide-dependent cushing's syndrome.

Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome has been reported to occur either in unilateral adrenal adenoma or in bilateral macronodular adrenal hyperplasia. A 33-yr-old woman with Cushing's syndrome was found to have two 2.5- to 3-cm nodules in the right adrenal on computed tomography scan; the left adrenal appeared normal except for the presence of a small 0.8 x 0.6-cm nodule. Uptake of iodocholesterol was limited to the right adrenal. Plasma morning cortisol was 279 nmol/L fasting and 991 nmol/L postprandially, and ACTH remained suppressed. Plasma cortisol increased after oral glucose (202%) or a lipid-rich meal (183%), but not after a protein-rich meal (95%) or iv glucose (93%); the response to oral glucose was blunted by pretreatment with 100 microg octreotide, sc. Plasma cortisol and GIP levels were positively correlated (r = 0.95; P = 0.0001); cortisol was stimulated by the administration of human GIP iv (225%), but not by GLP-1, insulin, TRH, GnRH, glucagon, arginine vasopressin, upright posture, or cisapride orally. A right adrenalectomy was performed; GIP receptor messenger ribonucleic acid was overexpressed in both adrenal nodules and in the adjacent cortex. Histopathology revealed diffuse macronodular adrenal hyperplasia without internodular atrophy. Three months after surgery, fasting plasma ACTH and cortisol were suppressed, but cortisol increased 3.6-fold after oral glucose, whereas ACTH remained suppressed; this was inhibited by octreotide pretreatment, suggesting that cortisol secretion by the left adrenal is also GIP dependent. We conclude that GIP-dependent nodular hyperplasia can progress in an asynchronous manner and that GIPR overexpression is an early event in this syndrome.

Adrenal Glands↗

International concerted action on collaboration in telemedicine: G8 sub-project 4.

The main objective of G-7/8 Global Healthcare Applications sub-project 4 is to enable an international concerted action on collaboration in telemedicine. To promote and facilitate the implementation of telemedicine or health telematics networks around the world, it was felt necessary to solve certain key issues. Five thematic solution-seeking FORUMS are each addressing a specific item. The first FORUM held in Montréal, Canada on May 28-30 1998 focussed on Interoperability of telemedicine and telehealth systems. Other FORUMS address other themes such as: Impacts of Telemedicine on health care management (Regensburg, Germany, November 21-23 1998); Evaluation and Cost Effectiveness of Telemedicine (Melbourne, Australia, February 19-20 1999); Clinical and technical quality and standards (Washington, USA, April 29-30 1999); Medico-legal aspects of national and international applications (Oxford, UK, fall 1999). The main objective of these FORUMS is to arrive at best practices through consultation amongst experts who seek together the best solutions to facilitate global international telemedicine networks. Towards this goal, G-8 sub-project-4 will also conduct the IMPACT (International Multipoint Project of Advanced Communication in Telemedicine) feasibility study which will aim at conducting multipoint exchanges between telemedicine units in the academic centers of the participating G-8 and other countries. More detailed information on this project and summaries of the initial FORUMS are found on our Web site at www.g7sp4.org.

Emergency Medical Services↗

Theory of use behind telehealth applications.

A variety of telehealth applications have been implemented throughout the industrialized world. Given that telehealth has yet to become routine in the practices of physicians, the impact of such applications on health care management remains difficult to identify. Only by becoming integrated into the 'normal practice' of clinicians can telehealth facilitate smooth communications in health care delivery processes. In this paper we demonstrate the importance of developing a 'theory of use', describing how clinicians are expected to use teleconsultation in their daily activities. By employing Giddens' Structuration Theory, we can develop a clear vision of the utilization of telehealth, and a better framework with which to assess its added value for health care delivery. We illustrate this claim by referring to our research on the Quebec Inter-Regional Telemedicine Network. In this study we compare the 'theory of use' behind the telemedicine network with the perceptions of physicians regarding their needs in terms of communications and access to expert advice. The breach between the theory and the perceptions of physicians may help to explain how the utilization of telehealth could be enhanced, and how new and sustainable routines for its integration into the health care system might be created.

Diffusion of Innovation↗