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Christian Richard

Publications and source records attributed to Christian Richard.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.

BACKGROUND: Associations between schizophrenia (SCZ) and polymorphisms at the regulator of G-protein signaling 4 (RGS4) gene have been reported (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18). Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles. METHODS: In an effort to resolve the role for RGS4 in SCZ susceptibility, we undertook a genotype-based meta-analysis using both published and unpublished family-based and case-control samples (total n = 13,807). RESULTS: The family-based dataset consisted of 10 samples (2160 families). Significant associations with individual SNPs/haplotypes were not observed. In contrast, global analysis revealed significant transmission distortion (p = .0009). Specifically, analyses suggested overtransmission of two common haplotypes that account for the vast majority of all haplotypes. Separate analyses of 3486 cases and 3755 control samples (eight samples) detected a significant association with SNP 4 (p = .01). Individual haplotype analyses were not significant, but evaluation of test statistics from individual samples suggested significant associations. CONCLUSIONS: Our collaborative meta-analysis represents one of the largest SCZ association studies to date. No individual risk factor arose from our analyses, but interpretation of these results is not straightforward. Our analyses suggest risk due to at least two common haplotypes in the presence of heterogeneity. Similar analysis for other putative susceptibility genes is warranted.

Case-Control Studies↗
PubMed2006

Passive leg raising predicts fluid responsiveness in the critically ill.

OBJECTIVE: Passive leg raising (PLR) represents a "self-volume challenge" that could predict fluid response and might be useful when the respiratory variation of stroke volume cannot be used for that purpose. We hypothesized that the hemodynamic response to PLR predicts fluid responsiveness in mechanically ventilated patients. DESIGN: Prospective study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: We investigated 71 mechanically ventilated patients considered for volume expansion. Thirty-one patients had spontaneous breathing activity and/or arrhythmias. INTERVENTIONS: We assessed hemodynamic status at baseline, after PLR, and after volume expansion (500 mL NaCl 0.9% infusion over 10 mins). MEASUREMENTS AND MAIN RESULTS: We recorded aortic blood flow using esophageal Doppler and arterial pulse pressure. We calculated the respiratory variation of pulse pressure in patients without arrhythmias. In 37 patients (responders), aortic blood flow increased by > or =15% after fluid infusion. A PLR increase of aortic blood flow > or =10% predicted fluid responsiveness with a sensitivity of 97% and a specificity of 94%. A PLR increase of pulse pressure > or =12% predicted volume responsiveness with significantly lower sensitivity (60%) and specificity (85%). In 30 patients without arrhythmias or spontaneous breathing, a respiratory variation in pulse pressure > or =12% was of similar predictive value as was PLR increases in aortic blood flow (sensitivity of 88% and specificity of 93%). In patients with spontaneous breathing activity, the specificity of respiratory variations in pulse pressure was poor (46%). CONCLUSIONS: The changes in aortic blood flow induced by PLR predict preload responsiveness in ventilated patients, whereas with arrhythmias and spontaneous breathing activity, respiratory variations of arterial pulse pressure poorly predict preload responsiveness.

Aorta↗
PubMed2006

Regional differences in adipose tissue metabolism in women: minor effect of obesity and body fat distribution.

Studies comparing adipose tissue metabolism in central versus peripheral fat depots have generated equivocal data. We examined whether regional differences in abdominal subcutaneous and omental adipose tissue metabolism in women exist and whether they persist across the spectrum of body fatness and abdominal adiposity values. We measured adipocyte size; lipoprotein lipase (LPL) activity; and basal, isoproterenol-, forskolin-, and dibutyryl cAMP-stimulated lipolysis in adipose tissue or mature adipocytes isolated from the omental and subcutaneous fat depots in a sample of 55 healthy women undergoing elective gynecological surgery. Measures of body fat mass and body fat distribution were also obtained by dual-energy X-ray absorptiometry and computed tomography. Subcutaneous adipocytes were significantly larger than omental adipocytes (P < 0.0001). LPL activity expressed as a function of cell number was significantly higher in subcutaneous versus omental adipose tissue (P < 0.0001). Basal, isoproterenol-stimulated, dibutyryl cAMP-stimulated (10(-3) mol/l) and forskolin-stimulated (10(-5) mol/l) lipolysis (expressed as a function of cell number) were all significantly higher in subcutaneous versus omental adipocytes (P < 0.05 to P < 0.0001). However, the response of omental adipocytes to lipolytic stimuli tested (fold increase over basal level) was significantly greater in magnitude compared with subcutaneous adipocytes (P < 0.01). These differences were relatively constant across total body fat mass and visceral adipose tissue area tertiles. In conclusion, compared with adipocytes from the omental fat compartment, subcutaneous adipocytes are larger, have higher LPL activity, and are more lipolytic on an absolute basis, which may reflect a higher fat storage capacity in this depot in women. In contrast, omental adipocytes display greater relative responsiveness to both adrenergic receptor-and postreceptor-acting agents compared with subcutaneous adipocytes. Overall and visceral obesity have only minor effects on regional differences in adipose tissue metabolism.

Adipocytes↗
PubMed2005

Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians.

The regulator of G-protein signaling (RGS) and RGS-like proteins are a diverse family of over 30 molecules that function as GTPase activating proteins for Galpha subunits of the Gq and Gi families of heterotrimeric guanine nucleotide-binding proteins (G proteins). By accelerating GTPase activity, RGS proteins drive G proteins into their inactive GDP-bound forms. G-protein coupled dopamine, metabotropic glutamate, and other neurotransmitter receptors can be modulated by RGS4, the predominant form in brain. The recent finding of decreased RGS4 mRNA expression in post-mortem brains from schizophrenic patients, coupled with the map position of RGS4 to a region previously linked to schizophrenia, as well as other biological data, prompted the investigation of the gene as a disease candidate. Multiple family-based and case-control association studies have been conducted, with modest and conflicting support for particular single nucleotide polymorphism (SNP) markers and SNP marker haplotypes. The present case-control analysis of 568 patients and 689 controls, one of the largest single studies to date, failed to confirm support for association of particular RGS4 SNP alleles, or for association of any particular four, three, or two SNP haplotype.

Adult↗
PubMed2005

Clinical review: interpretation of arterial pressure wave in shock states.

In critically ill patients monitored with an arterial catheter, the arterial pressure signal provides two types of information that may help the clinician to interpret haemodynamic status better: the mean values of systolic, diastolic, mean and pulse pressures; and the magnitude of the respiratory variation in arterial pressure in patients undergoing mechanical ventilation. In this review we briefly discuss the physiological mechanisms responsible for arterial pressure generation, with special focus on resistance, compliance and pulse wave amplification phenomena. We also emphasize the utility of taking into consideration the overall arterial pressure set (systolic, diastolic, mean and pulse pressures) in order to define haemodynamic status better. Finally, we review recent studies showing that quantification of respiratory variation in pulse and systolic arterial pressures can allow one to identify the mechanically ventilated patients who may benefit from volume resuscitation.

Arteries↗
PubMed2005

Esophageal Doppler monitoring predicts fluid responsiveness in critically ill ventilated patients.

OBJECTIVE: To test whether fluid responsiveness can be predicted by the respiratory variation in aortic blood flow and/or the flow time corrected for heart rate monitored with esophageal Doppler. DESIGN AND SETTING: Prospective study in a 24-bed medical intensive care unit of a university hospital. PATIENTS: 38 mechanically ventilated patients with sinus rhythm and without spontaneous breathing activity in whom volume expansion was planned. INTERVENTIONS: The aortic blood flow was measured using an esophageal Doppler monitoring device before and after fluid infusion (500 ml NaCl 0.9% over 10 min). The variation in aortic blood flow over a respiratory cycle between its minimal and maximal values was calculated. The flow time was also measured. MEASUREMENTS AND RESULTS: Aortic blood flow increased by at least 15% after volume expansion in 20 patients (defined as responders). Before fluid infusion the respiratory variation in aortic flow was higher in responders than in nonresponders (28+/-12% vs. 12+/-5%). It significantly decreased after volume expansion (18+/-11%) in responders only. A respiratory variation in aortic flow before volume expansion of at least 18% predicted fluid responsiveness with a sensitivity of 90% and a specificity of 94%. Flow time increased with fluid infusion in responders and nonresponders. A flow time corrected for heart rate below 277 ms predicted fluid responsiveness with a sensitivity of 55% and a specificity of 94%. The area under the ROC curve generated for variation in aortic blood flow ABF was greater than that generated for flow time. CONCLUSIONS: The respiratory variation in aortic blood flow reliably predicts fluid responsiveness in patients with sinus rhythm and without breathing activity.

Aorta↗
PubMed2005

[Shock].

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed2004

Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women.

We examined expression and activity of steroid aldoketoreductase (AKR) 1C enzymes in adipose tissue in women. AKR1C1 (20alpha-hydroxysteroid dehydrogenase; 20alpha-HSD), AKR1C2 (3alpha-HSD-3), and AKR1C3 (17beta-HSD-5) are involved mainly in conversion of progesterone to 20alpha-hydroxyprogesterone and inactivation of dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol. Abdominal subcutaneous and omental adipose tissue biopsies were obtained during abdominal hysterectomies in seven women with low visceral adipose tissue (VAT) area and seven age- and total body fat mass-matched women with visceral obesity. Women with elevated VAT areas were characterized by significantly higher omental adipose tissue 20alpha-HSD and 3alpha-HSD-3 mRNA abundance compared with women with low VAT accumulations (1.4- and 1.6-fold differences, respectively; P < 0.05). Omental and subcutaneous adipose tissue 3alpha-HSD activities were significantly higher in women with high vs. low VAT areas (P < 0.05 for both comparisons). Total and visceral adiposities were positively associated with omental 20alpha-HSD mRNA level (r = 0.75, P < 0.003 for fat mass; r = 0.57, P < 0.04 for VAT area) and omental 3alpha-HSD-3 mRNA level (r = 0.68, P < 0.01 for fat mass; r = 0.74, P < 0.003 for VAT area). Enzyme activities in both depots were also positively correlated with adiposity measures. Omental adipose tissue enzyme expression and activity were positively associated with omental adipocyte size and LPL activity. In conclusion, mRNA abundance and activity of AKR1C enzymes in abdominal adipose tissue compartments are positive correlates of adiposity in women. Increased progesterone and/or dihydrotestosterone reduction in abdominal adipose tissue may impact locally on fat cell metabolism.

20-Hydroxysteroid Dehydrogenases↗
PubMed2004

Expression and activity of 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in abdominal subcutaneous and omental adipose tissue in women.

We examined the expression and activity of 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) in abdominal adipose tissue in women. This recently characterized enzyme from the aldoketoreductase 1C family is responsible for the conversion of progesterone into 20alpha-hydroxyprogesterone. Abdominal sc (SC) and omental (OM) adipose tissue biopsies were obtained from a sample of 32 women aged 47.7 +/- 5.9 yr (body mass index 27.6 +/- 5.0 kg/m(2)) undergoing abdominal hysterectomies. Body composition and body fat distribution measurements were performed before the surgery by dual-energy x-ray absorptiometry and computed tomography, respectively. The expression of 20alpha-HSD was determined by real-time RT-PCR, and its activity was measured in whole-tissue homogenates. mRNA and activity of the enzyme were detected in both the SC and OM fat depots, the two measures being significantly higher in the SC compartment. Women characterized by a visceral adipose tissue area of 100 cm(2) or greater had an increased 20alpha-HSD conversion rate in their OM adipose tissue, compared with women without visceral obesity (13.99 +/- 2.07 vs. 7.92 +/- 0.83 fmol/microg protein per 24 h, P < 0.05). Accordingly, a positive correlation was found between OM adipose tissue 20alpha-HSD activity and computed tomography-measured visceral adipose tissue area (r = 0.36, P < 0.05). Significant positive correlations were also found between OM 20alpha-HSD activity and OM adipocyte diameter (r = 0.49, P < 0.05) and OM adipose tissue LPL activity (r = 0.36, P = 0.06). In conclusion, 20alpha-HSD activity and mRNA were detected in SC and OM adipose tissue in women, and OM 20alpha-hydroxylation of progesterone was highest in women with visceral obesity. Additional studies are required to establish whether local conversion of progesterone may impact on the metabolism and function of adipocytes located within the abdominal cavity.

20-Hydroxysteroid Dehydrogenases↗