Role of Ca2+ in the action of adrenocorticotropin in cultured human adrenal glomerulosa cells.

The present report details the role of Ca2+ in the early events of ACTH action in human adrenal glomerulosa cells. Threshold stimulations of both aldosterone and cAMP production were obtained with a concentration of 10 pM ACTH, an ED50 of 0.1 nM, and maximal aldosterone stimulation (5.5-fold increase over control) at 10 nM ACTH. ACTH also induced a sustained increase of intracellular calcium ([Ca2+]i) with maximal stimulation of 1.6 +/- 0.1-fold over control values. This increase does not involve mobilization of calcium from intracellular pools since no response was observed in Ca2+-free medium or in the presence of nifedipine, suggesting the involvement of Ca2+ influx by L-type Ca2+ channels. This was confirmed by patch clamp studies that demonstrated that ACTH stimulates L-type Ca2+ channels. Moreover, the Ca2+ ion is not required for ACTH binding to its receptor, but is essential for sustained cAMP production and aldosterone secretion after ACTH stimulation. These results indicate that, in human adrenal glomerulosa cells, a positive feedback loop between adenylyl cyclase-protein kinase A-Ca2+ channels ensures a slow but sustained [Ca2+]i increase that is responsible for sustained cAMP production and aldosterone secretion.

[Percutaneous therapies for aortic and mitral valvular disease]. / Traitement percutané des atteintes valvulaires aortiques et mitrates.

For a few years, numerous articles and lectures were published as well as presented at major meetings on percutaneous therapies for valvular heart disease. Calcific aortic stenosis in the elderly is frequent and difficult to manage with 1/3 of patients not operated because of high surgical risks. In 2002, the first percutaneous aortic valve bioprosthesis was implanted. Since then, several hundreds of interventions were performed with 2 different valves (Cribier-Edwards, Corevalve). Preliminary results are encouraging. Regarding percutaneous mitral valve interventions, balloon valvuloplasty for stenosis is well established but treatment modalities for mitral insufficiency remain complex due to a wide disease spectrum. Therefore, development is more at a preliminary level and the window of application may be narrower, but still attractive.

[Chronic total occlusion: the last frontier of the interventional cardiology?]. / Occlusions coronaires chroniques: dernière frontière de la cardiologie interventionnelle?

Recanalization of chronic total occlusion remains a challenge for the interventional cardiologist and accounts for 10-20% of all angioplasty procedures in high-volume catheterization laboratories. During the last few years, development in guidewires and devices as well as the emergence of new techniques from japanese centers resulted in a higher success rates in experienced operator's hands. The impact of drug eluting stents on restenosis has improved longterm outcome after chronic total occlusion successfull recanalization. This procedure requires time, patience from the operator and does also expose the patient to increased radiation and contrast administrations. In symptomatic patients, when recanalization is successful, the clinical outcome and the event free survival are improved.

Ralstonia mannitolilytica in cystic fibrosis: A new predictor of worse outcomes.

BACKGROUND: Patients with Cystic Fibrosis are subject to repeated respiratory tract infections, with recent increasing isolation of unusual pathogens. Ralstonia species have lately been isolated at our institution, an organism historically frequently misidentified as Burkholderia or Pseudomonas. The prevalence of Ralstonia spp. in cystic fibrosis populations has yet to be determined, along with its clinical implications. CASE PRESENTATIONS: Seven patients out of the 301 followed at our cystic fibrosis clinic have had Ralstonia strains identified in their respiratory tract. Most strains identified were multi-drug resistant. After aquisition of Ralstonia spp., the patients' clinical course was characterized by more frequent and more severe respiratory infections along with prolonged hospitalizations, greater decline of lung function, and greater mortality. The mortality rate in this group of patients was 86%. No other factor that could explain such a dramatic evolution was identified upon review of patient data. Some of the strains involved were recognized as clones on Pulse Field Electrophoresis Gel, raising the question of person-to-person transmission. CONCLUSION: New pathogens are identified with the evolution of the microbiota in cystic fibrosis respiratory tracts. In our cohort of patients, acquisition of Ralstonia spp. was associated with dramatic outcomes in terms of disease acceleration and raised mortality rates. It is of critical importance to continue to better define the prevalence and clinical impact of Ralstonia in cystic fibrosis populations.

Stent placement to prevent restenosis after angioplasty in small coronary arteries.

BACKGROUND: Lesions in small-diameter vessels (<3 mm) define a group with distinct clinical and morphological characteristics. There is an inverse relationship between vessel size and angiographic restenosis rate. This study assessed whether stents reduce angiographic restenosis in small coronary arteries compared with standard balloon angioplasty. METHODS AND RESULTS: We randomly assigned 351 symptomatic patients needing dilatation of 1 native coronary vessel between 2.3 and 2.9 mm in size to angioplasty alone (n=182) or stent implantation (n=169). The primary end point was angiographic restenosis at 6 months. Secondary end points included death, myocardial infarction, bypass surgery, and target vessel revascularization in hospital and at 6 months. There were no significant differences between groups in terms of major in-hospital complications. There was a trend toward fewer in-hospital events in the stent group (3% versus 7.1% in angioplasty group, P=0.076). Crossovers to stent occurred in 37 patients (20.3%). Repeat angiography at 6-month follow-up was performed in 85.3% of patients. Angiographic restenosis occurred in 28% of the stent group and 32.9% of the angioplasty group (P=0.36). Target vessel revascularization was required in 17.8% versus 20.3% of patients (P=0.54), respectively. CONCLUSIONS: Stenting and standard coronary angioplasty are associated with equal restenosis rate in small coronary arteries. With a lower in-hospital complication rate, stenting may be a superior strategy in small vessels.

Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.

BACKGROUND: The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina. METHODS AND RESULTS: We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction. CONCLUSIONS: Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.

Technetium-99m sestamibi tomography in patients with spontaneous chest pain: correlations with clinical, electrocardiographic and angiographic findings.

The sensitivity and specificity of technetium-99m hexakis-2-methoxy-2-isobutyl-isonitrile (sestamibi) single-photon emission computed tomographic (SPECT) imaging for the diagnosis of coronary artery disease were studied in 45 patients admitted to the hospital for clinical suspicion of unstable angina. Only patients without prior myocardial infarction were included and all patients had technetium-99m sestamibi injection and a 12-lead electrocardiogram (ECG) during and less than or equal to 4 h after an episode of chest pain. Coronary angiography performed in all patients during hospitalization showed significant coronary artery disease (greater than or equal to 50% luminal diameter reduction) in 26 of the 45 patients. The SPECT studies obtained after injection of technetium-99m sestamibi during an episode of spontaneous chest pain showed a sensitivity of 96% for the detection of coronary artery disease; the 12-lead ECG obtained at the time of the injection had a sensitivity of 35%. With the patient in the pain-free state, respective sensitivity values were 65% and 38%. Specificity for the radionuclide study was 79% during pain and 84% in the pain-free state; for the ECG, it was 74% both during and between episodes of pain. The site of the perfusion defect corresponded to the most severe coronary artery lesion in 88% of patients. The severity of the perfusion defect correlated with the extent of coronary artery disease: the defect score was 5.3 +/- 3.3 with one-vessel disease, 4.9 +/- 2.8 with two-vessel disease and 10.5 +/- 5.0 with three-vessel disease (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatibility aspects of new stent technology.

Stent implantation represents a major step forward since the introduction of coronary angioplasty. As indications continue to expand, better understanding of the early and late biocompatibility issues appears critical. Persisting challenges to the use of intracoronary stents include the prevention of early thrombus formation and late neointima development. Different metals and designs have been evaluated in animal models and subsequently in patients. Polymer coatings have been proposed to improve the biocompatibility of metallic stents or to serve as matrix for drug delivery and they are currently undergoing clinical studies. The promises of a biodegradable stent have not yet been fulfilled although encouraging results have recently been reported. Continuous low dose-rate brachytherapy combining the scaffolding effect of the stent with localized radiation therapy has witnessed the development and early clinical testing of radioactive stents. The combined efforts of basic scientists and clinicians will undoubtedly contribute to the improvement of stent biocompatibility in the future.

Modulation of a Ca(2+)-activated K+ channel by angiotensin II in rat adrenal glomerulosa cells: involvement of a G protein.

In the present study, we demonstrate the presence of Ca(2+)-activated K+ channels in rat glomerulosa cells. We find that angiotensin II (Ang II) inhibits this charybdotoxin-sensitive current. The effect of Ang II was dose-dependent with an inhibition constant (Ki) of 0.98 nM and a maximal effect observed at 200 nM. Time course of the blockage was as rapid as the one induced by charybdotoxin. This effect is mediated by the AT1 receptor subtype of Ang II, since it is blocked by DUP 753 but is unaffected by CGP 42112. Activation of protein kinase C by phorbol dibutyrate (1 microM) or dialysis of the cell with inositol 1,4,5-triphosphate (20 microM) were ineffective in blocking the current. However, experiments done with GDP beta S and GTP gamma S indicated that a G protein was involved. The inhibitory effect of Ang II was not pertussis toxin-sensitive, which excludes Gi protein, but was abrogated if an antibody raised against the alpha-subunit of the Gq/11 protein was present in the patch pipette medium. Further analysis showed that the Ca(2+)-activated K+ channel was able to modulate the membrane potential according to the level of intracellular calcium concentration ([Ca2+]i). Whereas a thapsigargin-induced increase in [Ca2+]i hyperpolarized the membrane, this effect was not observed when Ang II was used to increase [Ca2+]i because of the blockage of the Ca(2+)-activated K+ current. The blockage of Ca(2+)-activated K+ current by Ang II would result in a synergistic effect on the Ang II-induced depolarization, thus favoring Ca2+ influx, an event essential to secretion.

Inhibition of the T-type Ca2+ current by the dopamine D1 receptor in rat adrenal glomerulosa cells: requirement of the combined action of the G betagamma protein subunit and cyclic adenosine 3',5'-monophosphate.

Modulation of ionic Ca2+ currents by dopamine (DA) could play a pivotal role in the control of steroid secretion by the rat adrenal glomerulosa cells. In the present study, we report that DA decreases the T-type Ca2+ current amplitude in these cells. The use of pharmacological agonists and antagonists reveals that this effect is mediated by activation of the D1-like receptors. Modulation by cAMP is complex inasmuch as preincubation of the cells with 8-Br-cAMP or the specific adenylyl cyclase inhibitor, 2',3'-dideoxyadenosine, have no effect per se, but prevent the DA-induced inhibition. The inhibitory effect of DA was abolished by addition of GDPbetaS to the pipette medium but not by pertussis toxin. If a cell is dialyzed with medium containing G alpha(s)-GDP, the inhibitory effect is reduced and cannot be recovered by the addition of GTPgammaS, indicating that the alpha(s) is not involved, but rather the betagamma-subunit. Indeed, DA-induced inhibition was mimicked by G betagamma in the pipette and 8-Br-cAMP in the bath. Similarly, G betagamma release from the activation of the AT1 receptor of angiotensin II did affect the current amplitude only in the presence of 8-Br-cAMP in the bath. The mitogen-activated protein kinase cascade, which can be activated by receptors coupled to Gs, was not involved as shown by the lack of activation of p42mapk by DA and the absence of effect of the mitogen-activated protein kinase inhibitor, PD 098059, on the DA-induced inhibition. Because the binding of G betagamma-subunits to various effectors involves the motif QXXER, we therefore tested the effect of the QEHA peptide on the inhibition of the T-type Ca2+ current induced by DA. The peptide, added to the medium pipette (200 microM), abolished the effect of DA. We conclude that the presence of the G betagamma and an increase in cAMP concentration are both required to inhibit the T-type Ca2+ current in rat adrenal glomerulosa cells.

Spectrofluorimetric and image recordings of spontaneous and lectin-induced cytosolic calcium oscillations in Jurkat T cells.

Intracellular variations in Ca2+ concentrations have been measured in single Jurkat T lymphocyte variants (77 6.8 and E6.1) using Fura-2 as a probe. Under basal conditions, the cytosolic Ca2+ level is stable but some cells show spontaneous Ca2+ oscillations (frequency, 0.30 +/- 0.06 Hz). These oscillations are sensitive to the external concentration of Ca2+ since they can no longer be observed when the bathing solution is replaced (superfusion) with a Ca(2+)-free medium or when a Ca2+ chelator (EGTA) is added. Various changes in the cytosolic concentration of Ca2+ ([Ca2+]i) can be observed when the cells are exposed to the mitogenic lectin phytohemagglutinin (PHA, 80 nM). For instance, in the case of non-oscillating cells, the lectin induces either a rapid increase in [Ca2+]i that is followed by a sustained response (plateau) or it triggers Ca2+ spikes. In the case of experiments done in Ca(2+)-free medium, only the initial spike was observed. In the case of spontaneously oscillating cells, PHA induces a rapid increase in [Ca2+]i that is followed by a plateau where oscillations are absent. In every case, the PHA-dependent Ca2+ response is abrogated in a Ca(2+)-free medium. Computer simulations based on the model of Goldbeter et al. [27] show that the various Ca2+ responses of Jurkat cells are related to the cytosolic level of free Ca2+. Video imaging analyses show that the cellular Ca2+ responses are not homogeneous whether the observations are made in spontaneously oscillating Jurkat cells or when they are exposed to PHA.

Characterization of K+ and Ca2+ ionic currents in glomerulosa cells from human adrenal glands.

Ionic currents of primary cultured glomerulosa cells from human adrenal glands were studied with the patch-clamp technique. Two types of outward K+ currents and two types of inward Ca2+ currents were described. The transient outward K+ current activated at potential positive to -40 mV and demonstrated a marked time-dependent inactivation. It was blocked by 4-aminopyridine but not tetraethylammonium. A second type of outward current activated rapidly at the depolarization onset and then increased slowly with no time-dependent inactivation. The transient inward T-type Ca2+ current was activated for potential positive to -60 mV with a maximal current amplitude at -30 mV and zero current voltage at +40 mV; it was completely inactivated for membrane potential positive to -40 mV. The pharmacological studies of the T-type channel showed that Ni2+ was a potent blocker but that the channel was not sensitive to dihydropyridine. The long-lasting inward Ca2+ current was activated for potentials positive to -20 mV with a maximum current amplitude at +70 mV. This current was increased by the agonist Bay K 8644 and blocked by the antagonist nifedipine; in addition, it was blocked by Cd2+ but less sensitive to Ni2+. This study revealed that glomerulosa cells from human adrenal demonstrated the presence of K+ and Ca2+ currents similar to those found in rat and bovine cells. Moreover, the main stimuli of aldosterone secretion, ACTH and angiotensin II, induce an increase in aldosterone secretion which is inhibited in a Ca(2+)-free external medium.

A Ras-dependent chloride current activated by adrenocorticotropin in rat adrenal zona glomerulosa cells.

In the present study, we report that ACTH induces a transient chloride current. The lack of correlation between ACTH-induced cAMP production and amplitude of the Cl- current, as well as the absence of stimulation by forskolin or 8Br-cAMP indicated that the ACTH-induced current was not cAMP-dependent. We explored the possibility that one or several elements of the Ras/Raf MAPK cascade were involved. Indeed, we found that ACTH at 10(-10) M induced activation of Ras. Inhibition of the current by QEHA peptide, a Gbetagamma sequestrant, demonstrated that Gbetagamma subunits transduced the message. Blockage of the Ras activation using an inhibitor of farnesyl transferase (BZA-5B) or the monoclonal antibody H-Ras(259) abrogated the current. Moreover, the addition of Ras-GTPyS in the pipette medium gave rise to the Cl- current. Treatment of the cells with BZA decreased the aldosterone secretion induced by 10(-10) M ACTH but not that induced by 10(-8) M ACTH, confirming the involvement of Ras in steroid secretion. We conclude that ACTH triggers a Cl- current through the activation of the Ras protein by Gbetagamma subunits. This current, activated at physiological ACTH concentrations (1 to 100 pM) where cAMP production is very low, could play a significant role in aldosterone production.

Early quantitative coronary angiography of saphenous vein grafts for coronary artery bypass grafting harvested by means of open versus endoscopic saphenectomy: a prospective randomized trial.

OBJECTIVE: Endoscopic saphenectomy is associated with a decreased incidence of wound complications without an increase in histologic trauma or endothelial dysfunction in published reports. Concern remains about the patency of saphenous vein grafts harvested endoscopically and the development of early intimal hyperplasia. The purpose of this study was to compare early quantitative coronary analysis of saphenous vein grafts used for coronary artery bypass grafting harvested with the open versus endoscopic techniques. METHODS: Forty patients undergoing primary coronary artery bypass grafting surgery with at least 1 saphenous vein graft were randomized preoperatively to open versus endoscopic saphenectomy with bipolar cauterization of side branches. Quantitative coronary angiography was performed a mean of 3 months (range, 1-9 months) after the operation. RESULTS: There was no statistically significant difference in the patency rates of internal thoracic artery grafts between the open and endoscopic groups and no statistically significant difference in the patency rates of saphenous vein grafts between both groups (85.2% vs 84.4%, P =.991). Quantitative coronary angiography showed no difference in graft stenosis (>or=50% of the internal diameter of the graft) in the body of the saphenous vein grafts in the open versus endoscopic saphenectomy groups (3.7% vs 0%, P =.280). CONCLUSION: Angiographic appearance and patency rates of saphenous vein grafts harvested with the endoscopic technique are similar to those of saphenous vein grafts harvested with the open technique. These results support the use of endoscopic saphenectomy because of the known lower incidence of wound and infectious complications and superior functional results.

Nitinol versus stainless steel stents: acute thrombogenicity study in an ex vivo porcine model.

Acute and subacute stents thrombosis along with thrombus mediating neointimal proliferation within the stent struts remain major concerns in coronary stenting. Up to date, there is an obvious lack of data on the thrombogenicity of stent materials in physiological conditions. This study was performed to compare the relative thrombogenicity of nitinol versus stainless steel stents. Nitinol stents were laser cut to reproduce the exact geometry of the stainless steel Palmaz stents and tested in an ex vivo AV shunt porcine model under controlled conditions. Nitinol stents presented only small amounts of white and/or red thrombus principally located at the strut intersections while Palmaz stents clearly exhibited more thrombus. As a result, 125I-fibrin(ogen) adsorption and (111)I-platelets adhesion were significantly lower on nitinol than on stainless steel devices (36%, p = 0.03 for fibrin(ogen) and 63%, p = 0.01 for platelet). These results were confirmed by scanning electron observations showing different thrombus morphologies for nitinol and stainless steel. Along with the unique mechanical properties of nitinol, its promising haemocompatibility demonstrated in our study may promote their increasing use for both peripheral and coronary revascularization procedures.

Lipase and pancreatic amylase activities in tissues and in patients with hyperamylasemia.

Lipase, pancreatic amylase, and total amylase activities were measured in nondiseased and diseased human pancreatic tissues and in six different locations of the human digestive system. In addition, it was determined whether serum lipase and pancreatic amylase tests could replace the total amylase test to improved diagnostic efficiency in the evaluation of acute pancreatitis in hyperamylasemia patients. Nondiseased pancreatic tissue contained 4.5 times more lipase activity than total amylase activity. Diseased pancreatic tissue contained less activity for both lipase and total amylase compared to normal tissue. The total amylase activity of the pancreas was comprised solely of pancreatic amylase. Tissue obtained from six different anatomic locations in the digestive system contained 35 to 45 times less lipase and total amylase activity compared to the pancreas. Total amylase activity of the digestive system tissues were comprised of 25% pancreatic and 75% salivary isoamylases. Lipase, pancreatic amylase, and total amylase levels also were determined in serial serum samples from 17 consecutive hyperamylasemia patients admitted with possible acute pancreatitis. The serum lipase level remained higher than normal longer than either the total amylase and pancreatic amylase levels. In patients with hyperamylasemia of pancreatic origin, a poor correlation was observed at admission between serum pancreatic amylase and serum lipase. Not all patients with elevated lipase had an elevated pancreatic amylase level and vice versa. However, in every patient pancreatic disease would have been detected by the elevation of either lipase or pancreatic amylase levels. Diagnostic efficiency for pancreatic disease using serum pancreatic amylase, lipase, and total amylase tests was 94.1%, 76.5%, and 64.7%, respectively. These data suggest that lipase and pancreatic amylase tests are specific for the pancreas and might be considered replacements for total amylase as the stat or routine laboratory test for the diagnosis of pancreatic tissue injury.

Fluorescent peptide hormones: development of high affinity vasopressin analogues.

Highly potent and specific peptide hormone analogues with fluorescent reporter groups are current research goals. Until now, however, only moderately potent analogues have been described. We report here several types of vasopressin (VP) analogues with different fluorophores attached to the peptide. In a first series, fluorophores were attached to the free epsilon amino function of [des-amino1-lysine8]VP (dLVP), producing agonistic analogues. In a second series, reporter groups were added to the N-terminal of open-chain antagonist structures. The biological activities of these analogues were assessed by two different sets of experiments: 1) The measurement of their binding affinities towards the V1a-vasopressin receptor subtype from WRK1 cells or rat liver membrane preparations; 2) Their ability to stimulate the phospholipase C activity in WRK1 cells. As expected, a simple acylation of fluorophores to dLVP resulted in a considerable loss of affinity. If however, the Lys8 side chain was extended through double Schiff-base formation with glutaraldehyde-ethylenediamine followed by reduction to an aminoalkyl aminoalkylamine, single fluorophores could be added without loss of affinity compared to VP. The open-chain analogues, on the other hand, while displaying weak affinity, nevertheless exhibited pure antagonistic behavior.

The oblique effect with colour defined motion throughout the visual field.

We assessed the extent of the oblique effect (OE) and the meridional orientation effect (MOE) for a chromatic motion task using red/green gratings throughout an 80 degrees visual field. Four different stimulus orientations were tested. Generally, sensitivity to chromatic motion decreased with increasing eccentricity regardless of the visual field meridian. Also, sensitivity was highest for horizontal or vertical gratings, thus supporting the presence of an OE rather than of a MOE. The strength of the OE varied between subjects, but was present from the fovea to 20 degrees of eccentricity. At 40 degrees of eccentricity, chromatic motion was always perceived but the grating orientation did not consistently influence chromatic motion sensitivity. The present study confirmed our previous results on chromatic motion sensitivity and isoluminance ratios throughout the visual field. In addition, our data show that the chromatic system can exhibit OEs at lower spatial frequencies than is observed for the achromatic system.

Isoluminance and chromatic motion perception throughout the visual field.

Isoluminance and chromatic motion perception for red/green gratings were measured throughout an 80 deg visual field. Generally, the red/green isoluminance values changed with increasing eccentricity, i.e., observers increased the red luminance contrast for a fixed green luminance contrast. Enlarging the target size (to compensate for the cone density changes with eccentricity) and decreasing the spatial frequency (to compensate for receptive field property changes with eccentricity) did not change the isoluminance values within the central 20 deg, but the isoluminance ratios decreased beyond 20 deg. Our manipulations did not entirely compensate for a given eccentricity, which implies the need for a post-receptoral scaling function for the perception of drifting chromatic stimuli. Further, the results for isoluminance show heterogeneity between the visual field meridians where the red to green luminance ratio tends to be greater in the superior visual field. In our present conditions, chromatic motion was always perceived (up to 40 deg of eccentricity), but sensitivity generally decreased with increasing eccentricity. The inferior visual field was found to be the most sensitive to chromatic motion. We propose that the lower visual field and not the superior visual field is specialized for colour motion information.

Bioindicator and exposure data for a population based study of manganese.

Exposure data and bioindicators were obtained for a study whose objective was detection of early manifestations of manganese (Mn) neurotoxicity in a population with potential environmental exposure. The study included persons with no history of neurotoxic workplace exposure in Southwest Quebec, drawn from seven postal code regions, defining a set of geographically contiguous zones. Blood samples were analyzed for total Mn (MnB), lead (PbB), total mercury (HgT) and serum iron (FeS). Drinking water samples from participants' residences were analyzed for manganese (MnW). At 4 sites, limited 24-hour high volume air samples for total particulates (TP) and PM10, were analyzed for Mn and Pb. Sociodemographic and dietary information was obtained by self-administered questionnaire. The geometric mean (GM) for MnB values (n = 297) was 7.14 micrograms/L. Levels of MnB in women (n = 156; GM 7.50 micrograms/L) were significantly higher than in men (n = 141; GM 6.75 micrograms/L). No relationship was found between MnB and PbB or HgT. FeS was significantly higher in men (GM 18.38 mumol/L) than women (GM 15.0 mumol/L). For women, MnB was correlated to FeS, with a tendency to decrease with increasing age. For men, no relationship was found between MnB levels and either FeS or age, although FeS showed a strong inverse relationship with age. The 24-hour mean levels of MnTP at the 4 sites varied between 0.009 microgram/m3 and 0.035 microgram/m3; intersite differences were not significant. For Mn in PM10 (MnPM10), mean values ranged from 0.007 microgram/m3 to 0.019 microgram/m3; intersite differences were significant. A total of 278 MnW samples were obtained, 16 from residences served by wells. The GM for MnW was 4.11 micrograms/L (range: 0.50-71.1 micrograms/L, excluding wells; MnW for wells ranged from non-detectable to 158.9 micrograms/L. Individually, there was no relation between MnW and MnB. Geographic analysis of the MnB and MnW data by an algorithm grouping contiguous postal code zones, combined with air data, lead to definition of a geographic parameter, distinguishing two regions relative to a former manganese alloy plant, which contributed significantly to MnB. A multiple regression model was developed, explaining 6.7% of the variability in MnB (F = 5.12; p < 0.001); when controlling for gender, geographic region with higher levels of airborne manganese and the frequency of consumption of cereals and leaf vegetables contributed positively to MnB levels, while serum iron was negatively related.