Biomedical subjects

M Lambert

Publications and source records attributed to M Lambert.

At least 55 records · Page 3Linked to original sources

PubMed2001

Determinants of lipid level variability in French-Canadian children with familial hypercholesterolemia.

The wide variability in the biochemical expression of familial hypercholesterolemia (FH) is only partly explained by mutational heterogeneity in the low density lipoprotein receptor (LDLR) gene. In the current study, we measured this biochemical variability in a group of children heterozygous for the >15-kb LDLR gene deletion (n=67) and examined the contribution of apolipoprotein (apo) E and B allelic variations to this phenotypic variability. Variances of total cholesterol (TC), LDL-C, and apoB concentrations and of the ratio of TC to high density lipoprotein cholesterol (HDL-C) were increased in FH subjects compared with controls. However, after taking the means into account, the coefficients of variation showed that the variability of LDL-C and apoB concentrations was smaller for FH than for controls and that the variability of TC and of the ratio TC to HDL-C was similar between both groups. The epsilon2/3 genotype was associated with lower mean TC, LDL-C, and apoB concentrations in FH. The magnitude of this effect was smaller in controls than in FH. Indeed, the percentages of total variance of TC, LDL-C, and apoB attributable to the apoE locus were 19.9%, 18.1%, and 11.8%, respectively, in FH cases and 5.9%, 7.4%, and 6.0%, respectively, in controls. We did not detect any effect of the apoB insertion/deletion polymorphism on lipid traits in FH children. However, in controls, we observed a strong interaction between apoE and apoB genotypes on apoB concentrations and on TC to HDL-C ratios. Our study reemphasizes the important role of apoE in lipid metabolism and illustrates that the effects of allelic variations on lipid traits are context dependent.

Apolipoproteins B↗

PubMed2001

Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis.

To test the hypothesis that sarcoidosis is associated with an intravascular leakage of lung epithelium secretory proteins, the occurrence and determinants in serum of sarcoid patients of CC16, a small size and readily diffusible lung-specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated. CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients with established sarcoidosis and of 117 healthy subjects matched for age, sex and smoking status. Stepwise regression analysis was used to identify extrapulmonary variables of CC16 changes in serum. These changes were then compared with biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as well as with the number of CC16 immunostaining cells on bronchial or pulmonary biopsy samples. CC16 concentration in serum of sarcoid patients was significantly increased, compared to their matched controls (25.9 +/- 16.2 versus 13.9 +/- 5.2 microg x L(-1)). In nonsmoking patients without significant renal impairment, CC16 in serum increased with the severity of the chest radiograph and computed tomography changes, and was on average 50-100% higher when parenchymal involvement was present. Sarcoid patients had, however, normal levels of CC16 in BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples, suggesting that an increased secretion of CC16 in the sarcoid lung is very unlikely, and that the elevation of CC16 in sarcoidosis results from an increased intravascular leakage of the protein across the air-blood barrier. The present study suggests that CC16 in serum might provide a useful tool to noninvasively evaluate the damage and increased permeability to proteins of the air-blood barrier associated with sarcoidosis.

Adult↗

PubMed2001

Myocardial microangiopathy associated with antiphospholipid antibodies.

Myocardial thrombotic microangiopathy is a well described post-mortem finding in patients with the catastrophic antiphospholipid (APL) syndrome. However, it has been only very rarely imaged in living patients. Here, we report two patients with APL antibodies presenting with scintigraphic, electrocardiographic and/or echocardiographic evidence of (sub)acute myocardial ischaemia, despite a normal coronary angiography. Formal proof of a thrombotic microangiopathy was obtained by a kidney biopsy in one patient. We emphasize the value of 99mTc-MIBI (2-methoxy isobutyl isonitrile) exercise stress myocardial scintigraphy for the detection of cardiac microangiopathy associated with the APL syndrome.

Adult↗

PubMed2000

Vasopressin V1a receptor signaling in a rat choroid plexus cell line.

A new cell line was derived from primary culture of rat choroid plexus (RCP) by immortalization with the TSOri minus adenovirus. The selected clone expressed vasopressin V1a receptors at a density of 64,000 sites per cell, and a K(d) of 7.2 nM. Addition of vasopressin to the RCP cells induced a transient calcium peak comparable to V1a receptor signalling in different expression systems. This [Ca(2+)](i) increase was dose-dependent with an EC(50) of 22 nM vasopressin. Similar [Ca(2+)](i) increase was elicited by addition of serotonin, angiotensin II, endothelin-1, and bradykinin. Heterologous desensitization of V1a receptor was observed in RCP cells exposed to the phorbol ester PMA or following stimulation of other receptors coupled to the phosphoinositide pathway. Positive immunolabelling with Factor VIII, Flt1 and CD 34 antibodies suggests that this new RCP cell line originated from endothelial cells of rat choroid plexus.

Animals↗

PubMed2000

[Conversion from typical to atypical neuroleptics. Guidelines for ambulatory and inpatient treatment].

The introduction of atypical antipsychotics has presented new options for the pharmacological treatment of schizophrenic patients. It is assumed that in the near future, neuroleptic medication will shift from conventional to atypical antipsychotics for an increasing number of patients. The present article addresses guidelines for the conversion from conventional to atypical neuroleptics in inpatient and outpatient settings.

Ambulatory Care↗

PubMed2000

Markers of tissue hypoperfusion in pediatric septic shock.

OBJECTIVE: To describe measurements of global oxygenation parameters, markers of splanchnic hypoperfusion and those of metabolic activity related to cellular energy production among critically ill children with septic shock. DESIGN: Clinical study of a series of cases. PATIENTS AND PARTICIPANTS: 11 previously healthy children with septic shock admitted to the pediatric intensive care unit (ICU) of a university hospital. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Oxygen consumption, oxygen delivery (DO(2)), serum bicarbonate, arterial pH, gastric intramucosal pH (pHi), gastroarterial carbon dioxide tension gradient, serum lactate, pyruvate, lactate to pyruvate ratio (L/P), ketone body ratio, and the esterified to free carnitine ratio were measured serially at 0, 6, 12, 24, 36, and 48 h after admission to the pediatric ICU. All children survived. One patient failed to show supranormal DO(2) ( > 570 ml/min per m(2)). Normalization of serum bicarbonate and lactate were associated with patient recovery. One patient presented an increasingly abnormal L/P ratio with normal lactate levels, suggesting an increased utilization of pyruvate rather than an increased cytosolic redox potential. Although values of gastric pHi < 7.30 were observed in 43 % of samples, serial measurements in individuals showed significant variability and unpredictable trends. Free fatty acid concentrations, ketone body production, and carnitine levels remained within the normal range. CONCLUSIONS: In this study, trends in serum bicarbonate and lactate somewhat characterized the recovery of children with septic shock. Based on our data, it is unclear how other markers may have been used to modify therapy.

Adolescent↗

PubMed2000

Ambient pH signalling in ascomycetous yeasts involves homologues of the Aspergillus nidulans genes palF and paIH.

In Yarrowia lipolytica, the transcription factor Rim101p mediates both pH regulation and control of mating and sporulation. Like its homologues PacC of Aspergillus nidulans and Rim101p of Saccharomyces cerevisiae, Y1Rim101p is activated by proteolytic C-terminal processing, which occurs in response to a signal transduced by a pathway involving several PAL gene products. We report here the cloning and sequencing of two of these genes, PAL2 and PAL3. PAL2 encodes a putative 632-residue protein with six possible transmembrane segments, which differs from the transmembrane proteins Rim9p of S. cerevisiae and Pall of A. nidulans, but is homologous to A. nidulans Pa1H and to the product of the ORF YNL294c, a predicted polypeptide of unknown function in S. cerevisiae. PAL3 encodes an 881-residue polypeptide that is homologous to PalF of A. nidulans and to a newly identified putative polypeptide of S. cerevisiae. Both PAL2 and PAL3 are expressed constitutively, regardless of ambient pH. Mutations in these genes affect growth at alkaline pH and sporulation in both Y. lipolytica and in S. cerevisiae. They affect invasiveness of haploid strains in S. cerevisiae only, and conjugation in Y. lipolytica only. These results highlight the conservation of the Pal pathway initially described in A. nidulans.

Amino Acid Sequence↗

PubMed2000

[Bronchiolitis obliterans with organized pneumonia: a rare complication of primary Gougerot-Sjögren syndrome].

INTRODUCTION: Bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by plugs of granulation tissue in bronchioles, alveolar ducts and alveoli. This pulmonary disorder has been reported in some cases in relation to drug consumption (D-penicillamine, amiodarone), with bacterial or viral infections (Mycoplasma pneumoniae, HIV), and with systemic diseases, such as rheumatoid arthritis. To our knowledge, only three cases of association BOOP-Sjögren's syndrome have been reported. EXEGESIS: We report three new cases of BOOP. These patients presented a primary Sjögren's syndrome without clinical or biological abnormalities suggestive of other autoimmune diseases. Initial presentation was an acute pulmonary disorder mimicking a bacterial pneumonia. Two patients had cutaneous vasculitis and the third vasculitic neuropathy. Corticosteroid therapy was begun and was quickly successful. None of the patients presented a relapse of BOOP. CONCLUSION: The incidence of BOOP is probably underestimated in patients with primary Sjögren's syndrome without cutaneous vasculitis. In case of pneumonia with antibiotic resistance, an immunological mechanism should be considered.

Adrenal Cortex Hormones↗

PubMed2000

Ultrasonographic diagnosis of testicular torsion by emergency physicians.

Testicular torsion has an incidence of one case per 4,000 men/boys. Most frequently affected are pubescent boys. Average testicular salvage rate is only 50%, and infertility can result Testicular torsion remains problematic for emergency physicians (EPs) as clinical diagnosis can be difficult and other testicular pathology can present similarly. In many institutions there are delays in obtaining Doppler or Scintigraphy studies during off-hours. We report two cases of testicular torsion diagnosed by the treating EPs using power Doppler in the emergency department (ED). Rapid diagnosis of torsion led to successful salvage of the affected testicle in both cases. These represent the first cases for emergency screening ultrasound examinations (ESUEs) of testicular torsion in the literature. Rapid technological advances over the last decade have brought portable equipment with high-resolution capability to the bed-side for EPs, who should consider using it more frequently to evaluate testicular torsion.

Adolescent↗

PubMed2000

Lung function study and diffusion capacity in anorexia nervosa.

STUDY OBJECTIVES: In humans, malnutrition alters the respiratory system in different ways. It impairs the ventilatory drive, decreases respiratory muscle strength and reduces immune competence. In addition, typical emphysema-like changes were demonstrated in starved animals. The presence of emphysema has never been demonstrated in starved humans. Our objective was to investigate whether pulmonary emphysema occurs in anorexia nervosa by means of a pulmonary function study. POPULATION AND METHOD: We examined 24 women aged between 14 and 38 years (nine smokers). We studied the lung function including lung volumes, ventilatory capacity, maximal respiratory pressures and transfer factor, as well as PaO2. RESULTS: All respiratory tests were within normal limits with the exception of decreased maximal inspiratory (59% of predicted values) and expiratory pressures (35%), and increased residual volume (162%). Diffusion capacity (98.1 +/- 16.2%) and transfer coefficient (98.4 +/- 16.2%) were also normal. The diffusion coefficient was lower in current smokers than in those who had never smoked (P < 0.01), a difference similar to that calculated from existing reference values for transfer factor for smokers and nonsmokers. CONCLUSION: In anorexia nervosa, pulmonary function tests are within normal limits with the exception of maximal pressures and residual volume. Diffusion capacity is not decreased. The present results within the limitations of the used method are not compatible with the hypothesis of starvation-induced pulmonary emphysema.

Adolescent↗

PubMed2000

Pharmacokinetics of ketoprofen enantiomers after intravenous administration of racemate in camels: effect of gender.

The pharmacokinetics of ketoprofen (KP) enantiomers were studied in ten female and eight male camels after a single intravenous dose (2.0 mg/kg) of racemic KP. A high performance liquid chromatographic (HPLC) method was developed for the quantitation of the R- and S-enantiomers without derivatization of the samples using a S,S-Whelk-01 chiral stationary phase column. The data collected (median and range) were as follows: the areas under the curve to infinity (AUC) (microg/mL per h) were 22.4 (13.5-29.7) and 19.8 (13.8-22.1) for R- and S-KP, respectively, in female camels while the corresponding values in male camels were 16.0 (12.9-22.4) and 14.4 (11.0-19.3). In both sexes, the AUC for the R-enantiomer was significantly larger than that of the S-enantiomer. Total body clearances (Cl(t)) were 44.6 (33.7-74.1) and 50.6 (45.2-72.4) mL/kg per h for R- and S-KP, respectively, in female camels and were 62.8 (44.6-77.8) and 69.6 (51.8-91.1) mL/kg per h for R- and S-KP, respectively, in male camels. In both sexes of camels, the Cl(t) values for R-KP were significantly lower than its corresponding antipode. The steady-state volumes of distribution (Vss) were 97.9 (82.8-147.2) and 102.0 (90.1-169.0) mL/kg for R- and S-KP, respectively, in female camels and were significantly different from each other, while the respective values in male camels were 151.5 (105.3-222.3) and 154.0 (114.7-229.0) mL/kg but were not significantly different from each other. The volumes of distribution (area) followed a similar pattern, where the values for R- and S-KP in female camels were 118.5 (95.6-195.2) and 137.6 (115.8-236.2) mL/kg, respectively, and the respective values in male camels were 215.6 (119.1-270.1) and 229.1 (143.3-277.4) mL/kg. The elimination half-lives (t1/2beta) were 1.88 (1.42-2.34) h and 1.83 (1.67-2.26) h for R- and S-KP, respectively, in female camels and were significantly different from each other, while the corresponding values in male camels were 2.11 (1.50-4.20) and 2.33 (1.52-3.83) h for R and S-KP, respectively, but were not significantly different from each other. The mean residence time followed a similar pattern. All pharmacokinetic parameters for R- and S-KP in female camels were significantly different from their corresponding values in male camels. The extent of protein binding for R- and S-KP was evaluated in vitro by ultrafiltration. The extents of protein binding for R- and S-KP were not significantly different from each other when each enantiomer was supplemented separately. However, when the enantiomers were supplemented together, protein binding of R-KP was significantly higher than that of S-KP in female but not in male camels.

Animals↗

PubMed2000

Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children.

BACKGROUND: Several studies have examined the association of the methylenetetrahydrofolate reductase (MTHFR) genotype with plasma homocysteine in adults, but few studies have been performed in children. OBJECTIVE: We measured the concentrations of plasma total homocysteine, folate, and vitamin B-12 in a group of healthy fasting children and related these to MTHFR genotype. DESIGN: After the subjects fasted, blood samples were collected into EDTA-containing tubes. Plasma, red blood cells, and the buffy coat were immediately stored at -80 degrees C for biochemical and molecular analyses. Plasma total homocysteine was determined by HPLC. Folate and vitamin B-12 were measured by a double-labeled radioimmunoassay, and the genotypic analysis was performed by polymerase chain reaction amplification of genomic DNA extracted from blood leukocytes. RESULTS: Plasma homocysteine concentrations correlated negatively with folate and vitamin B-12(,) but positively with age (P: < 0. 0001). Whereas folate and vitamin B-12 accounted for 27% and 19% of the variation in homocysteine, respectively, age accounted for 48% of the variation. When the cohort was divided into older (>10 y) and younger (</=10 y) individuals, folate was significantly lower in the older individuals who were homozygous for the mutation (T/T) than in those who were homozygous for the wild-type allele (C/C). Homocysteine was higher in the T/T group than in both the C/C and C/T subgroups aged >10 y. CONCLUSION: Our data show that in a healthy pediatric population, MTHFR genotype played a significant role in determining homocysteine concentrations in older (>10 y), nutritionally stressed children.

Adolescent↗

PubMed2000

Longitudinal analysis of bone mineral density in pre-menopausal female systemic lupus erythematosus patients: deleterious role of glucocorticoid therapy at the lumbar spine.

OBJECTIVE: To evaluate whether bone loss occurs over time in pre-menopausal systemic lupus erythematosus (SLE) patients. METHODS: We performed a longitudinal bone mineral density (BMD) analysis in a group of 35 pre-menopausal female SLE patients. Lumbar spine and hip (total and sub-regions) BMDs were measured twice 21 +/- 11 (mean +/- S.D.) months apart by dual-energy X-ray absorptiometry. RESULTS: In the whole cohort of SLE patients, significant bone loss was observed at the lumbar spine (-1.22%/yr) but not at the total hip. Further analyses indicated that lumbar spine bone loss (-2.12%/yr) occurred exclusively in the subgroup of patients who had taken a mean prednisolone daily dose >7.5 mg between the two BMD measurements. Moreover, bone loss was more important in patients who had previously received a cumulative prednisolone dose </=5 g by the time of their first BMD evaluation. CONCLUSIONS: These results, by demonstrating a loss of lumbar spine bone over time in pre-menopausal SLE patients given glucocorticoid (GC) therapy, strongly support the use of preventive treatment to minimize GC-induced osteoporosis in pre-menopausal female SLE patients given prednisolone daily doses >7.5 mg.

Adult↗

PubMed2000

Dosage of conventional neuroleptic medication and subjective cognitive functioning in schizophrenia.

Subjective cognitive and perceptual disturbances as assessed with the Frankfurt Complaint Questionnaire (FCQ) were correlated with chlorpromazine equivalents in 40 schizophrenic inpatients, who were treated with conventional neuroleptics. In line with previous research using 'objective' neuropsychological tests, both correlations and partial correlations (controlling for the effects of psychopathology, extrapyramidal symptoms and length of illness) confirmed that higher neuroleptic doses significantly worsen several cognitive and perceptual domains (r = 0.44 -0.54; P < or = 0.005 -0.05) with the possible exception of mnestic functions (r = 0.21 -0.24, n.s.) and language (r = 0.37 -0.38, P < 0.1). The clinical importance of self-report scales for evaluating both the risks and benefits of neuroleptic treatment is discussed.

Adult↗

PubMed2000

Spontaneous haemoperitoneum from surreptitious ingestion of a rodenticide.

Superwarfarins have progressively replaced warfarin as rodenticides as they are more potent and have a longer anticoagulant activity. Human exposure may be complicated by spontaneous haemorrhage in various sites. We report the case of a 51-year-old woman who was admitted with spontaneous haemoperitoneum and intramural haematoma along the small intestine. After the evidence of a deficit of vitamin K1-dependent clotting factors (II, VII, IX, X), the patient admitted that she was chronically ingesting difenacoum. She was successfully treated with fresh frozen plasma and vitamin K1. Follow-up was not accepted.

4-Hydroxycoumarins↗

PubMed2000

Do emergency physicians save time when locating a live intrauterine pregnancy with bedside ultrasonography?

OBJECTIVE: To determine whether patients presenting to the emergency department (ED) with first-trimester pregnancy complications have a decreased length of stay (LOS) when a live intrauterine pregnancy (IUP) is diagnosed by emergency physicians (EPs). METHODS: This study was performed at an urban community ED with a residency program and an annual census of 65,000. A retrospective chart review from October 1995 to August 1998 identified 1,419 patients who received ultrasound examinations confirming live IUP in the first trimester with pain and/or bleeding. Two hundred seventy-seven of these patients received their ultrasound examinations from EPs; 1, 142 patients received a study from radiology and were not scanned by EPs. The LOSs for the two groups were compared and defined as the time from being placed into a room to discharge from the ED. Significance was determined using a two-tailed t-test. Median times with confidence intervals were calculated. RESULTS: When patients had a live IUP confirmed by an EP, the median LOS was 21% (59 min) less than those who received an ultrasound examination by radiology (p = 0.0001; 95% CI = 49 min to 1 hr 17 min). When evaluated by time of day, patients who presented after hours (6 PM to 6 AM) and were scanned by EPs spent 28% (1 hr 17 min) less time in the ED (p = 0.0001; 95% CI = 55 min to 1 hr 37 min). CONCLUSIONS: Emergency physicians identifying live IUP with bedside ultrasonography significantly decreased patients' LOSs in the ED. The decrease in LOS was most apparent for patients presenting during evening and nighttime hours.

Emergency Service, Hospital↗

PubMed2000

Paraoxonase activity is dramatically decreased in patients positive for anticardiolipin antibodies.

It has been reported that paraoxonase 1 (PON1) activity inhibits low-density lipoprotein (LDL) oxidation and modulates the risk of coronary heart disease. This study shows that autoantibodies (IgG) directed against modified LDL were increased in 71 patients positive for anticardiolipin antibodies. In a representative subgroup of these patients (n = 36) PON1 activity was dramatically decreased and the prevalence of the RR genotype of this enzyme tended to be increased in patients who had developed arterial thrombosis. This study suggests that PON1 abnormalities play a role in the antiphospholipid syndrome.

Adult↗

PubMed2000

Immobilized dimers of N-cadherin-Fc chimera mimic cadherin-mediated cell contact formation: contribution of both outside-in and inside-out signals.

Cell adhesion receptors of the cadherin family are involved in various developmental processes, affecting cell adhesion and migration, and also cell proliferation and differentiation. In order to dissect the molecular mechanisms of cadherin-based cell-cell adhesion and subsequent signal transduction to the cytoskeleton and/or cytoplasm leading to adapted cell responses, we developed an approach allowing us to mimic and control cadherin activation. We produced a dimeric N-cadherin-Fc chimera (Ncad-Fc) which retains structural and functional properties of cadherins, including glycosylation, Ca(2+)-dependent trypsin sensitivity and the ability to mediate Ca(2+)-dependent self-aggregation of covered microbeads. Beads covered with either Ncad-Fc or anti-N-cadherin antibodies specifically bound to N-cadherin expressing cells. Both types of beads induced the recruitment of N-cadherin, beta-catenin, alpha-catenin and p120, by lateral mobilization of preexisting cell membrane complexes. Furthermore, cadherin clustering elicited by Ncad-Fc beads triggered local accumulations of tyrosine phosphorylated proteins, a recruitment and redistribution of actin filaments, as well as local membrane remodeling. These results support a model where the adhesion of cadherin ectodomains is followed by clustering of cadherin/catenin complexes allowing signal transduction affecting both cytoskeletal reorganization and cytoplasmic signal mobilization (outside-in signaling). Interestingly, bead-cell binding was altered by agents promoting microfilament and microtubule depolymerization or tyrosine phosphorylation, indicating a possible regulation of the adhesive properties of the extracellular domain of N-cadherin by intracellular factors (inside-out signaling).

Animals↗