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Biomedical subjects

M Giroux

Publications and source records attributed to M Giroux.

At least 19 recordsLinked to original sources

Creatininuria in asthmatic children treated with a combination of glucocorticoid and beta-agonist.

We examined whether a combination of glucocorticoids and beta-agonists inhaled by asthmatics had an influence on the metabolism of L-arginine, an amino acid involved in the production of urea, creatinine, and NO that is known to play a significant role in asthma. After lung function tests, we assayed nitrates, urea, and creatinine and determined urinary osmolality in urine samples taken from groups of 129 children (10+/-3 years old) with mild-to-moderate asthma treated with different regimens of drugs. No significant differences in urinary urea levels were noted between the groups. On the other hand, the children treated by the combination of glucocorticoid and beta-agonist (n = 52) had a higher level of urinary creatinine (+40%, P < .001, and a higher creatinine/urea ratio (C/U) expressed as % mass= 5.98 +/- 2.44, P < .001) than did the untreated children (n = 43, C/U = 4.03 +/- 1.24), those treated with glucocorticoid (n = 23, C/U = 4.01 +/- 1.32) or beta-agonist alone (n = 11, C/U = 4.09 +/- 1.01) or control children of the same age (n = 20, C/U = 4.81 +/- .90). Children treated with beta-agonist alone had the lowest mean levels of urinary nitrates (P < .05). The children in group 1 whose C/U ratio was above 6 (n = 24) had a higher FVC (P < .02) and FEV1 (not significant (NS)). However, an overly high C/U may also be indicative of a deleterious influence on the biosynthesis of NO from arginine. Further investigations will be required to determine whether there is a relationship between C/U ratios and lung function parameters, and whether the urinary C/U ratio could be employed as a simple and noninvasive parameter for assessment of treatment in asthmatics.

Administration, Inhalation↗

Exhaled NH3 and excreted Nh4+ in children in unpolluted or urban environments.

Exhaled ammonia (NH3ex) was measured by chemiluminescence in a group of healthy children (n = 20) and in two groups of asthmatic children, one (Group 1) residing in a National Park in the mountains (n = 68) and other (Group 2) in an urban area (n = 52). We also determined urinary ammonia, nitrates, urea, sodium and potassium normalized to osmolarity. Unlike exhaled nitric oxide (NOex), NH3ex was not specific to asthma as the children in Group 2 and the controls exhaled more ammonia that did the children in Group 1 (14.3 +/- 10.2 and 14.8 +/- 10.3 vs. 5.6 +/- 4.7 ppb; P < .001, respectively). In the urban environment, all children, including the healthy controls, excreted more ammonia (P < .001) and potassium (P < .001) but less urea (P < .02) than did the children residing in the National Park. These manifestations of moderate metabolic acidosis would favor excretion of ammonia at the expense of urea. In the children residing in the National Park, positive correlations were observed between NH3ex and urinary ammonia, and nitrates, age and morphological parameters. The relationship with the morphological parameters is a reflection of the normal physiological formation of NH3ex. In the children residing in the urban area, the other endogenous source of NH3ex was attributed to a slight disturbance in acid-base balance. In conclusion, the measurement of NH3ex appeared of limited interest, although the higher urinary urea/NH4+ ratio in Group 1 (P < .0001), especially in the treated children, appeared to be linked to the lack of atmospheric pollutants in the National Park. Further experimentation is in progress to confirm these findings.

Air Pollutants↗

Exhaled NO in asthmatic children in unpolluted and urban environments.

BACKGROUND: NO production (NOex) in the airway epithelium is increased in asthmatic patients and is potently inhibited by anti-inflammatory treatments. The study was designed to compare the: (i) levels of NOex in two groups of asthmatic children residing in different environments (one in a national park in the mountains and the other in a large city) and (ii) the influence of glucocorticoids on levels of NOex between the children and those without treatment. METHODS: The measurements were performed during the same period in the two locations, 100 km apart. NOex was measured using a chemiluminescence analyzer in controls and two comparable groups of asthmatic children. The first group included 63 children (10+/-3 years) recruited from a specialized institution for asthmatic children, and the second group consisted of 46 asthmatic children (9+/-3 years) living in an urban area. A reference group of 17 healthy children residing in the same city was also studied. MEASUREMENTS AND RESULTS: The concentrations of NOex in children in the specialized institution were significantly lower (P<.001) than those in asthmatic children living in the city (5.1+/-2.4 vs. 13.8+/-9.3 ppb) and comparable to those in healthy controls (5.3+/-4.0 ppb). In the urban area, NOex levels increased when atmospheric pollution recorded on the previous day had increased. In contrast to that observed in the urban children, glucocorticoids had little influence on the levels of NOex in the children living in the specialized institution. CONCLUSIONS: Although these relationships need to be confirmed, our findings show that for the determination of NOex, specifying the quality of the environment, in particular, the purity of the air respired by asthmatic children, not only at the time of measurement but also over the previous days, is important.

Air Pollutants↗

Combined effect of ascorbic acid and gamma irradiation on microbial and sensorial characteristics of beef patties during refrigerated storage.

The present study was undertaken to evaluate the effect of ascorbic acid concentrations (0.03 to 0.5%) and irradiation doses (0.5 to 4 kGy) on microbial growth, color coordinates (L, a, and b), and sensory characteristics (taste and odor) of beef patties during storage at 4 +/- 1 degrees C. Ascorbic acid was also compared to citric acid at a similar pH value in order to differentiate the effects of ascorbic acid from those of pH reduction. Results showed significant reduction (p< or = 0.05) of aerobic plate counts (APCs) and total coliforms, and a significant interaction (p< or = 0.05) between ascorbic acid and irradiation dose was observed. The irradiation treatment had detrimental effects on redness, yellowness, and hue angle values of meat. However, incorporation of ascorbic acid into the meat before irradiation resulted in significant (p< or = 0.05) stabilization of color parameters. The color improvement obtained with ascorbic acid was not related to the pH reduction. Also, no significant detrimental effect on taste or odor was found in irradiated samples containing ascorbic acid.

Animals↗

Plasma complement C5 protects endothelial cells from polymorphonuclear neutrophil-derived, H2O2-mediated cytotoxicity.

BACKGROUND: In vitro studies suggest that polymorphonuclear neutrophils (PMN) can damage endothelial cells (EC) by releasing hydrogen peroxide. In vivo this can lead to anasarca secondary to capillary leakage of fluid, protein, and electrolytes. The result is multiple organ dysfunction syndrome, which is associated with high mortality. In vivo, circulating PMN-EC interactions take place in the presence of plasma, and we have shown previously that plasma affords protection to EC from PMN-mediated damage. METHODS: Human umbilical vein endothelial cells were primed with cytokines, cultured to a confluent monolayer, and coincubated with normal human PMNs. Cytotoxicity was assayed by gamma scintigraphy, plasma C5 was determined by sepharose column elution, and H(2)O(2) was assayed by R-Phycoerythrin fluorescence. RESULTS: Addition of C5, but not C3, to RPMI resulted in EC cytoprotection equivalent to adding whole serum. Removal of C5 from serum using F(ab')(2) rabbit IgG anti-human C5 coupled to CNBr-activated 4 sepharose beads resulted in significant loss of EC cytoprotection against H(2)O(2)-mediated damage, whereas adding back C5 restored the cytoprotection. C5 also reduced H(2)O(2)-mediated destruction of R-Phycoerythrin. CONCLUSIONS: The data suggest that the protection of EC against hydrogen peroxide-mediated damage is partly mediated through complement component C5.

Animals↗

Cyclooxygenase-2 expression in macrophages: modulation by protein kinase C-alpha.

Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for high levels of PG production during inflammation and immune responses. Previous studies with pharmacological inhibitors suggested a role for protein kinase C (PKC) in PG production possibly by regulating COX-2 expression. In this study, we addressed the role of PKC-alpha in the modulation of COX-2 expression and PGE2 synthesis by the overexpressing of a dominant-negative (DN) mutant of this isoenzyme in the mouse macrophage cell line RAW 264.7. We investigated the effect of various stimuli on COX-2 expression, namely, LPS, IFN-gamma, and the intracellular parasite Leishmania donovani. Whereas LPS-induced COX-2 mRNA and protein expression were down-regulated in DN PKC-alpha-overexpressing clones, IFN-gamma-induced COX-2 expression was up-regulated in DN PKC-alpha-overexpressing clones with respect to normal RAW 264.7 cells. Measurements of PGE2 levels revealed a strong correlation between PGE2 secretion and IFN-gamma-induced COX-2 mRNA and protein levels in DN PKC-alpha-overexpressing clones. Taken together, these results suggest a role for PKC-alpha in the modulation of LPS- and IFN-gamma-induced COX-2 expression, as well as in IFN-gamma-induced PGE2 secretion.

Adjuvants, Immunologic↗

Atmospheric NO, temperature and ischaemic heart disease. Study in Toulouse and its conurbation.

Over a period of 388 days, associations were sought between the occurrence of acute myocardial infarction (AMI), levels of atmospheric nitrogen-containing gases (NO, NO2, NH3), temperature and relative humidity. During this period, there were 282 AMI validated by the WHO-MONICA criteria. Analysis of the data revealed, a decrease in the area, in AMI, when daily nitric oxide levels were above 13 microg m(-3) and when the mean daily temperature was below 13 degrees C.

Air↗

Physiology of hypokinetic and hyperkinetic movement disorders: model for dyskinesia.

Although the basal ganglia have been implicated in the development of movement disorders since the 1940s, the exact role played by these structures has remained elusive. The development of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-monkey model of parkinsonism, and the recent resurgence of surgical therapy for the treatment of hypokinetic and hyperkinetic movement disorders has, however, led to an improved understanding of the pathophysiological mechanisms that underlie their development. In this article, we review the functional organization and examine the changes in neuronal activity that occur in the basal ganglia thalamocortical 'motor' circuit in these disorders. An alternative to the classic 'rate' model for Parkinson's disease is presented that incorporates the observed changes in neuronal activity, as well as additional neuronal pathways that contribute to these changes. Based on studies in animal models and humans with hyperkinetic movement disorders, it is postulated that dyskinesias develop as the result of a combination of excessive reductions in the mean discharge rate, altered patterns and increased synchronization of neurons in the internal segment of the globus pallidus. It is further postulated that the particular type of involuntary movement which develops also depends on the relative change in neuronal activity in the direct, indirect and alternative pathways. Support for these postulates is examined, and models for drug-induced dyskinesia, hemiballismus and dystonia are proposed.

Animals↗

Serum nitrates and creatinine in workers exposed to atmospheric nitrogen oxides and ammonia.

An epidemiological survey was carried out on 332 workers in a nitrogen fertilizer factory exposed to various levels of NO, NO2, NO3- and NH3. The population was divided into six groups as a function of the atmospheres in the different workshops and compared with a control group recruited outside the factory. We investigated the relations between the exposures of the different groups and serum levels of three nitrogen-containing derivatives involved in arginine metabolism: nitrates, creatinine and urea. The workers most exposed to the hydrogenated and oxygenated compounds of nitrogen were found to have the highest serum nitrates. Further analysis of the results showed that inhaled nitrogen oxides and ammonia were only partly responsible for the circulating nitrates. The excess nitrates were thought to have an endogenous origin due to inflammatory reactions induced by the pollutants, especially ammonia. In addition, we showed that the workers from the two groups exposed to both NO and NH3 had significantly elevated levels of serum creatinine (P < 0.001). The excess creatinine was thought to have derived from the interaction of the exogenous NO with arginine metabolites.

Adult↗

Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome.

BACKGROUND/PURPOSE: Although medullary thyroid carcinoma (MTC) can occur sporadically, in the pediatric population it is most often associated with the multiple endocrine neoplasia syndrome (MEN type 2). Traditional screening was based on evaluation of basal and stimulated serum calcitonin levels. The recent cloning of the MEN2 gene on the RET proto-oncogene of chromosome 10 now allows for testing of gene carrier status in individuals at risk who could benefit from prophylactic treatment. The current study was undertaken to determine the appropriate age for safe total prophylactic thyroidectomy. METHODS: Over a 16-year period, 12 patients with a family history of MEN2A and one with a MEN2B underwent total thyroidectomy and central neck dissection without parathyroid autotransplantation. Four patients (31%) were treated previously for Hirschsprung's disease. RESULTS: In seven patients (mean age, 11.8 years) undergoing biochemical screening for diagnosis, multifocal MTC and C cell hyperplasia (CCH) were found in all the resected specimens. Of six patients identified with genetic screening (mean age, 9.1 years), two had elevated stimulated calcitonin levels, one (age 14) had evidence of MTC, and one (age 6) had CCH. Four patients with normal calcitonin levels had no evidence of MTC (ages 6, 8, 10) but there was one occurrence of CCH (age 11). No permanent postoperative hypoparathyroidism or recurrent laryngeal nerve damage occurred in this series. With a mean follow-up of 4 years (range, 1 to 14 years), the overall disease-free survival is 100%. CONCLUSIONS: From this study the authors conclude that total thyroidectomy can be performed safely in children and should be the treatment of choice in patients with a family history of MEN2A carrying a germinal RET mutation even if the serum basal or stimulated serum calcitonin level is normal. Total thyroidectomy should be performed as early as 5 years of age before the occurrence of CCH or MTC.

Adolescent↗

Influence of maternal blood flow on the placental transfer of three opioids--fentanyl, alfentanil, sufentanil.

The placental transfer of three opioids used in peridural analgesia, fentanyl, alfentanil and sufentanil, and two reference substances, antipyrine and *H2O, was determined ex vivo in the human placental cotyledon system. (1) In the first set of experiments, the infusion rates were constant and fixed at physiological flow rates. Under these conditions, the magnitude of the materno-fetal transfer was in the following order: *H2O = antipyrine = fentanyl > alfentanil > sufentanil. No particular influence of molecular weight, lipophilia, pKa or the degree of ionization could be discerned. (2) In the second set of experiments, the influence of different flow rates, reflecting various pathophysiological conditions, was examined. There was a linear relationship between the maternal flow and the materno-fetal transfer of the three opioids. On the other hand, for antipyrine and tritiated water, the relationship was logarithmic, a difference attributed to the marked lipophilia of the opioids. (3) At high maternal flow rates, saturation was observed for all five substances due to the short duration of contact with the membrane. There were logarithmic relationships between the maternal flow and the materno-fetal transfer. (4) These findings emphasize the importance of the lipophilic and hydrophilic characteristics of drugs on placental transfer, especially in the event of fluctuations in maternal flow.

Alfentanil↗

[Surgical treatment of thyroid diseases in children].

UNLABELLED: In order to review the experience of a single institution with thyroid surgery and identify prognostic factors, we did a retrospective chart review of all patients who underwent thyroid surgery between 1980 and 1995. Fifty patients, 32 girls and 18 boys, underwent thyroid surgery. Clinical presentation include a thyroid nodule (36 patients), a family history of MEN syndrome with a positive pentagastrin stimulation test (10), diffuse nodular goitre (3) and a neonatal cervical mass (1). Radiologic investigation include ultrasonography in 58% of cases, radionucleide imaging in 70% of cases. The mean age at surgery was 13.3 years and the delay between onset of symptoms and diagnostic was 13 months. Twenty-one patients had a lobectomy +/- isthmectomy, 19 had a total thyroidectomy and 10 had a subtotal thyroidectomy. Nine patients required a second surgery to complete the surgical treatment, and perform a total or near total thyroidectomy when the final pathology showed a carcinoma. A well differentiated carcinoma was found in 52% of the patients, a medullary carcinoma in 20% and a benign lesion in 28% of cases. Nine patients had local or distant metastases at initial surgery. Post-op treatment consisted of suppressive hormonotherapy in all cases of cancer and radioactive iodine when recurrence occurred in 24% of patients and when metastasis where present. Survival remained at 100%. CONCLUSION: Thyroid nodules should be rapidly investigated in children because of a high potential of cancerous lesions. With an aggressive surgical treatment and post-op I131 for recurrent lesions and metastasis the prognostic remains excellent.

Adolescent↗

Effect of adrenaline on plasma concentrations of fentanyl during epidural anaesthesia for caesarean section.

The present study was designed to assess the effect of adrenaline on the plasma concentrations of fentanyl in mothers and umbilical vessels after epidural administration for caesarean section. Thirty patients undergoing elective caesarean section were allocated randomly into two groups. Group 1 (n = 16) received 100 microg fentanyl, 10 ml of 0.5% bupivacaine and 10 ml 2% lidocaine, while group II (n = 14) received 100 microg fentanyl, 10 ml of 0.5% bupivacaine with adrenaline 1:200 000, and 10 ml of 2% lidocaine with adrenaline 1:80 000. Blood samples were obtained from the maternal antecubital vein (MV) at various times up to 6 hours after epidural injection, and from umbilical vein (UV) and arteries (UA) at birth for determination of plasma fentanyl by radioimmunoassay. Fentanyl Cmax and Tmax in MV did not differ significantly between the two groups. In umbilical vessels, plasma fentanyl concentrations were comparable in the two groups: (0.12 +/- 0.08 ng ml(-1) and 0.13 +/- 0.08 ng ml(-1) in UV and 0.08 +/- 0.07 ng ml(-1) and 0.06 +/- 0.05 ng ml(1) in UA of groups I and II respectively). The maximum plasma concentration in UV was 0.24 ng ml(-1) in group I and 0.25 ng ml(-1) in group II. There was no significant correlation between umbilical vessel (vein or artery):MV ratio and dose to delivery interval and no difference between the two groups in Apgar score or umbilical cord pH.

Journal Article↗