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Biomedical subjects

J C Mercier

Publications and source records attributed to J C Mercier.

At least 19 recordsLinked to original sources
PubMed1995

Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis.

OBJECTIVE: To examine the incidence, risk factors, and outcome of severe sepsis in intensive care unit (ICU) patients. DESIGN AND SETTING: Inception cohort study from a 2-month prospective survey of 11,828 consecutive admissions to 170 adult ICUs of public hospitals in France. PATIENTS: Patients meeting clinical criteria for severe sepsis were included and classified as having documented infection (ie, documented severe sepsis, n = 742), or a clinical diagnosis of infection without microbiological documentation (ie, culture-negative severe sepsis, n = 310). MAIN OUTCOME MEASURES: Hospital and 28-day mortality after severe sepsis. RESULTS: Clinically suspected sepsis and confirmed severe sepsis occurred in 9.0 (95% confidence interval [CI], 8.5 to 9.5) and 6.3 (95% CI, 5.8 to 6.7) of 100 ICU admissions, respectively. The 28-day mortality was 56% (95% CI, 52% to 60%) in patients with severe sepsis, and 60% (95% CI, 55% to 66%) in those with culture-negative severe sepsis. Major determinants of both early (< 3 days) and secondary deaths in the whole cohort were the Simplified Acute Physiology Score (SAPS) II and the number of acute organ system failures. Other risk factors for early death included a low arterial blood pH (< 7.33) (P < .001) and shock (P = .03), whereas secondary deaths were associated with the admission category (P < .001), a rapidly or ultimately fatal underlying disease (P < .001), a preexisting liver (P = .01) or cardiovascular (P = .002) insufficiency, hypothermia (P = .02), thrombocytopenia (P = .01), and multiple sources of infection (P = .02). In patients with documented sepsis, bacteremia was associated with early mortality (P = .03). CONCLUSIONS: Only three of four patients presenting with clinically suspected severe sepsis have documented infection. However, patients with clinically suspected sepsis but without microbiological documentation and patients with documented infection share common risk factors and are at similarly high risk of death. In addition to the severity of illness score, acute organ failures and the characteristics of underlying diseases should be accounted for in stratification of patients and outcome analyses.

Adult↗
PubMed1995

Complete sequence of the ovine beta-casein-encoding gene and interspecies comparison.

The 9149-bp transcription unit encoding ovine beta-casein (Cas) and 4636 bp of 5' flanking region were completely sequenced. The gene is composed of nine exons and its overall organization is similar to that of its counterparts from other species. Intron 4, the largest, shares three similar stretches (sizes ranging from 0.1 to 0.3 kb) with the region upstream from the transcription unit. These common sequences are part of short interspersed nuclear elements (SINE) specific to Bovidae (Bov). Intron 4 contains two 274-bp Bov-A2 SINE in opposite orientation, as well as a full-length 569-bp Bov-B SINE. This latter SINE, also present in caprine intron 4, is missing in cattle. This suggests that the amplification of Bov-SINE has continued after the divergence of cattle from sheep and goats, assuming that the presently known sequences are representative of these species.

Amino Acid Sequence↗
PubMed1995

Is there a role for inhaled nitric oxide in pediatric ARDS?

Despite advances in ventilator management and use of extracorporeal lung support, mortality related to ARDS in pediatric patients has not been reduced over the past 20 years. Progressive respiratory failure, due to evolution of the primary illness or to complications of ventilator therapy, significantly contributes to poor outcome. ARDS is characterized by severe ventilation-perfusion mismatch and by pulmonary hypertension. Because of their side effects which affect systemic hemodynamic status or worsen intrapulmonary shunting, intravenous vasodilator trials have been of limited interest. Nitric oxide (NO) has been recognized as a gas with vasodilator properties. In neonates studies have shown that inhaled NO may have an important role in the therapy of persistent pulmonary hypertension. Inhaled NO in adults with severe ARDS has been shown to reduce pulmonary hypertension without producing systemic vasodilation. This reduction of pulmonary vascular resistances may reduce pulmonary edema formation, decrease vasoconstrictor response to cardiotonic agents, and improve biventricular function. In addition, arterial oxygenation seems to be increased by improved matching of ventilation with perfusion. Improvement of oxygenation with inhaled NO suggests that use of lower tidal volumes and FIO2 may be more successful. Until now, there are no published studies regarding NO administration in ARDS affecting nonneonatal pediatric patients. However, the results obtained in adults and newborns suggest that inhaled NO may be a useful adjuvant therapy of ARDS in children, possibly in association with other therapies. Even in adults it remains unclear whether therapy with inhaled NO can reduce morbidity and mortality. Prospectives and randomized studies are essential to assess the real utility of inhaled NO in ARDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Echocardiographic investigation of inhaled nitric oxide in newborn babies with severe hypoxaemia.

Nitric oxide inhalation can benefit newborn babies with right-to-left extrapulmonary shunt (EPS). Using doppler ultrasound, we compared the effects of nitric oxide on systemic oxygenation and mean pulmonary-blood-flow velocity (MPBFV) in severely hypoxic babies with or without EPS. With a median (interquartile range) dose of 20 (32) parts per million, oxygenation index decreased significantly in both groups (EPS, 49 [19] vs 11 [9]; non-EPS, 40 [11] vs 20 [13]). The decrease was significantly greater in the EPS group. MPBFV increased significantly in the EPS group (18 [4] vs 29 [8] m/s) only. Nitric oxide may improve systemic oxygenation in neonates with severe hypoxaemia secondary to EPS by increasing pulmonary blood flow, and in those without EPS by improving ventilation-perfusion matching.

Administration, Inhalation↗
PubMed1994

Creation and phenotypic analysis of alpha-lactalbumin-deficient mice.

alpha-Lactalbumin is an abundant milk-specific calcium metalloprotein which has an evolutionary relationship to lysozyme. It modifies the substrate specificity of a Golgi galactosyltransferase by forming the lactose synthetase binary complex. Lactose, together with other sugars and diffusible ions, is responsible for the osmotic pressure of milk. To assess the involvement of alpha-lactalbumin in lactogenesis, alpha-lactalbumin-deficient mice were created by disrupting the gene by homologous recombination in embryonic stem cells. Homozygous mutant mice are viable and fertile but females cannot feed their offspring. They produce a highly viscous milk that pups appear to be unable to remove from the mammary gland. This milk is rich in fat and protein and is devoid of alpha-lactalbumin and lactose. The phenotype of heterozygous mice was found to be intermediate, with a 40% decrease in alpha-lactalbumin but only a 10-20% decrease in the lactose content of their milk compared with wild-type animals. These results emphasize the key function of alpha-lactalbumin in lactogenesis and open new opportunities to manipulate milk composition.

Animals↗
PubMed1994

Doppler echocardiographic assessment of pulmonary circulation in severe respiratory failure of the neonate: an aid for extracorporeal lung support indications.

Extracorporeal lung support (ECLS) for newborns with acute respiratory failure has achieved increased popularity over the last decade. However, precise criteria for its implementation remain controversial. The aim of this study was to assess the value of Doppler echocardiography (DE) in 31 neonates with PaO2 of < or = 50 mmHg, FIO2 of 1, and optimal ventilation. Treatment included mechanical ventilation, paralysis, volume loading, vasopressors, and tolazoline. Markers indicative of ECLS (failure of maximal medical therapy, assessed by AaDO2 of more than 610 mm Hg beyond 8 hours and/or an oxygenation index (OI = mean airway pressure x FIO2%/postductal PaO2) of more than 40 beyond 4 to 6 hours) were present in 23 (group 1) and absent in eight (group 2). Shunt direction and systolic pulmonary arterial pressure (sPAP) calculated from tricuspid insufficiency velocity were assessed using DE. At the time of admission, sPAP was significantly higher in group 1 (62.1 v 43.7 mm Hg). On day 1, group 1 differed from group 2 in maximum sPAP value (73.2 v 44.4 mm Hg), PaCO2 (56.1 v 40 mm Hg), right-to-left shunting (85% v 25% of the patients), and pulmonary-to-systemic-pressure systolic ratio (sPAP:sSAP) (1.29 v 0.75). Patients with an sPAP:sSAP ratio of more than 1 and patients with high sPAP associated with high PaCO2 on day 1, all later (average, 10 hours later) fulfilled ECLS criteria; this suggests that DE assessment of pulmonary circulation may yield early and predictive markers of impending ECLS indication. Further confirmation of these results would help avoid unnecessary delays in ECLS implementation in newborns with severe respiratory failure.

Echocardiography, Doppler↗
PubMed1992

High expression of the caprine beta-casein gene in transgenic mice.

An 18-kb caprine genomic DNA fragment, comprising the beta-casein transcription unit with about 3-kb 5' and 6-kb 3' flanking regions, was microinjected into fertilized one-cell murine eggs. All nine lines of transgenic mice obtained expressed the transgene in their mammary glands, as demonstrated by Northern blot analysis of mRNA in miscellaneous tissues, and qualitative and quantitative analysis of caprine beta-casein in milk, using SDS/PAGE, Western blotting and rocket immunoelectrophoresis. Two lines produced milk containing up to 21-24 mg of the exogenous protein/ml, a yield which is roughly twice that found in goat milk. The yield reached at least 40 mg/ml in some progeny of crossbred G1 transgenic mice. Thus, the investigated gene appears to be a good candidate for making hybrid constructs that might promote an efficient production of valuable foreign proteins in milk.

Animals↗
PubMed1992

Sequence of the murine alpha-lactalbumin-encoding cDNA: interspecies comparison of the coding frame and deduced pre-protein.

The structure of the mouse alpha-lactalbumin-encoding mRNA was deduced from sequence analysis of eight cDNA clones. The almost full-length mRNA of 732 nucleotides [poly(A) tail excluded] and the deduced pre-protein share 85% and 86% homology with their rat counterpart, respectively. Interspecies comparison of the pre-protein showed the occurrence of an extra amino acid (aa) in the signal peptide and of two mutations affecting two reported invariant aa residues at positions 44 and 107, which weakens the assumption that both aa residues might play a significant structural and/or functional role.

Amino Acid Sequence↗
PubMed1992

Expression analysis of ruminant alpha-lactalbumin in transgenic mice: developmental regulation and general location of important cis-regulatory elements.

The bovine alpha-lactalbumin transgene with 750 bp and 336 bp of the 5' and 3' flanking region, respectively, is developmentally regulated as its endogenous counterpart in transgenic mice. Comparative expression analysis of three 5'-shortened constructs suggests that the region -477/-220 contains important cis-acting transcriptional elements. The level of expression of a long caprine alpha-lactalbumin transgene encompassing 8.5 kb and 9.5 kb of the 5' and 3' flanking region, respectively, was higher but still unrelated to the copy number. Expression of the transgenes and of endogenous milk-protein genes was tissue-specific. In contrast with a recent report, only low amounts of the relevant mRNA were detected in some skin samples, which suggests a possible contamination by mammary tissue.

Animals↗
PubMed1992

Molecular epidemiology unravels the complexity of neonatal Escherichia coli acquisition in twins.

Combined analysis of restriction fragment length polymorphism of regions of genes coding for rRNA (ribotyping) and esterase electrophoretic typing was used to document neonatal acquisition of Escherichia coli in twins. Our study shows vertical mother-to-infant transmission of one strain of E. coli to one twin and the development of neonatal septicemia with a distinct nonvirulent carboxylesterase type B1 E. coli strain for the other twin.

Adult↗
PubMed1992

[Continuous arteriovenous hemofiltration. Management in case of neonatal leucinosis].

BACKGROUND: Neonates with classic maple syrup urine disease (MSUD) undergo rapid neurological deterioration by the end of the first week of life. Exchange transfusion and peritoneal dialysis are the usual emergency treatment. Continuous arteriovenous hemofiltration (CAVHF) appears to be safe and more rapidly effective. CASE REPORT: Martin was born at the 37th week from a normal pregnancy. Abnormal movements of legs and lethargy appeared on the 7th day of life. Progressive brain dysfunction with coma led to intubation on the 13th day. A diagnosis of MSUD was immediately made and CAVHF was initiated and continued for 19 hours. The plasma leucine, valine and isoleucine levels fell from 2,248 to 275, 640 to 91 and 298 to 13 mumol/l, respectively. Neurologic improvement was dramatic, except for moderate hypertonia which lasted for the 2 following days. CONCLUSION: CAVHF is an appropriate treatment for very young patients with inborn errors of metabolism. It appears safer and more rapidly effective for eliminating branched-chain amino acids than other techniques, such as peritoneal dialysis with or without exchange transfusions. It also permits more rapid introduction of the specific diet.

Hemofiltration↗
PubMed1992

[Congenital diaphragmatic hernia. Value of preoperative stabilization].

Seventy-two patients with congenital diaphragmatic hernia (CDH) diagnosed in the first 12 hours of live have been reviewed retrospectively. Forty-eight patients born before 1985 (group I) were compared to 24 patients born between 1985 and 1989 (group II). The management was different for the 2 groups. Group I was operated on immediately. For group II, delayed surgery after stabilization was preferred. For this group, stability was sought before, during and after surgery. Therapy was first aimed at optimizing ventilation and oxygenation by way mechanical ventilation. Pharmacologic agents were used in an attempt to decrease pulmonary vascular resistance and improve cardiac output. The survival rate was 37.5% before 1985, 62.5% after 1985 (P less than 0.01). Main prognostic factors were Apgar score, paCO2, pH, ventilation index, alveolar-arterial difference in oxygen and oxygenation index. The stabilization before surgery improved the survival rate.

Carbon Dioxide↗
PubMed1991

Multiple mRNA species code for two non-allelic forms of ovine alpha s2-casein.

The two non-allelic forms of alpha s2-casein, occurring in ovine milk, differ by an internal deletion of nine amino acid residues, including both cysteine residues at positions 34 and 42 in the mature chain. Sequencing of several alpha s2-casein cDNA, isolated from the mammary cDNA library of a single lactating ewe, showed three new types which differed from that previously studied. In addition to the expected deletion of codons +34 to +42 affecting 30-40% of mRNA, another structural difference involving an internal stretch of 44 nucleotides in the 5' untranslated region, was found. S1-nuclease protection assays confirmed the existence of several types of the relevant mRNA and sequencing of in-vitro-amplified genomic DNA demonstrated the presence of the 44-nucleotide stretch in the alpha s2-casein transcriptional unit, thus ruling out the possibility of a cloning artefact. The different alpha s2-casein mRNA, four in terms of deletion and two in terms of nucleotide substitutions for a given ewe, can be readily explained by partial exon skipping and allelic differences, respectively. This assumption is well supported by the following observations: 5' and 3' ends of both deleted DNA fragments are similar to those of exons; sequences neighbouring the 44-nucleotide stretch of the genomic DNA perfectly match consensus sequences described for 3' and 5' ends of introns; the rather simple patterns observed on Southern blots of different enzymatic digests of genomic DNA strongly suggest the occurrence of only 1 copy alpha s2-casein gene/haploid genome. During the course of evolution, the alpha s2-casein-encoding gene has undergone many mutations and some of them might have occurred in regions corresponding to consensus splicing regions of the pre-mRNA. Thus, complete skipping of some exons might be responsible for the shorter sizes of rat and mouse alpha s2-casein mRNA. If so, the overall organization of the alpha s2-casein gene in the different species might be more similar than expected from structural comparisons of the cognate mRNA or caseins.

Amino Acid Sequence↗
PubMed1991

The bovine alpha-lactalbumin promoter directs expression of ovine trophoblast interferon in the mammary gland of transgenic mice.

A hybrid construct derived from ovine trophoblastin cDNA and bovine alpha-lactalbumin-encoding gene, was injected into the pronuclei of mouse eggs. In one of the resulting transgenic mouse lines, expression of the hybrid construct was detected and found to be limited to the mammary gland of lactating females which secreted active ovine trophoblastin. This strongly suggests that important cis-acting DNA sequences involved in tissue-specific expression of the bovine gene are located within the second half of the 3' untranslated region, or/and the proximal 5' and 3' regions flanking the transcriptional unit.

Animals↗
PubMed1991

Sequence of the goat alpha-lactalbumin-encoding gene: comparison with the bovine gene and evidence of related sequences in the goat genome.

The isolation and characterization of a genomic clone encoding goat alpha-lactalbumin (alpha LA) are described, and its sequence was aligned with that of its bovine counterpart. The 5'-flanking regions are highly homologous, but two small insertions were found in the goat sequence. One of these insertions fills the gap found in the so-called 'milk-box' consensus sequence of the bovine gene. Southern analysis indicates the presence of several alpha LA-related sequences in the goat genome, as previously observed in cow and sheep, which suggests that the relevant duplication event(s) occurred before divergence of these ruminant species.

Amino Acid Sequence↗
PubMed1991

Restriction fragment length polymorphism of ovine casein genes: close linkage between the alpha s1-, alpha s2-, beta- and kappa-casein loci.

Restriction fragment length polymorphism (RFLP) of ovine casein genes was investigated. Genomic DNA from 56 rams was digested with 10 restriction endonucleases and Southern blots probed with the four ovine casein cDNAs (alpha s1-, beta-, alpha s2- and kappa-Cn). Five enzymes, namely, BglI, PvuII, RsaI, TaqI and HindIII revealed nine different RFLPs. The inheritance of six of these polymorphisms was studied by segregation analysis of gametes in nine rams' families, and each of them could be related to the existence of alleles at the relevant casein locus. A close linkage between the four ovine casein genes was demonstrated since no recombination within the four pairs of loci examined, alpha s1-beta-Cn, alpha s1-kappa-Cn, beta-kappa-Cn and alpha s2-kappa-Cn, was observed in the progeny of double heterozygous rams. The casein genes are thus clustered in the ovine species as in the case of other mammals.

Alleles↗