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Background: Little is known about patient risk factors associated with environmental contamination.Aim: To evaluate the rate of environmental contamination and to investigate individual risk factors.Methods: A prospective cohort study was conducted. Each day, five rooms occupied by patients were selected. Five critical surfaces were systematically swabbed twice a day before and after cleaning. Clinical characteristics of all patients were collected. Logisitic regression was performed to evaluate the association between environmental contamination and patients' characteristics.Findings: A total of 107 consecutive patients were included and 1052 environmental samples were performed. Nineteen (18%) patients were known previously colonized/infected with a multidrug-resistant organism (MDRO). Respectively, 723 (69%) and 112 (11%) samples grew with ≥1 and >2.5 cfu/cm2 bacteria, resulting in 62 (58%) contaminated rooms. Considering positive samples with at least one pathogenic bacterium, 16 (15%) rooms were contaminated. By univariate and multivariate analysis, no variables analysed were associated with the environmental contamination. Considering contaminated rooms with >2.5 cfu/cm2, three factors were protective for environmental contamination: known MDRO carriers/infected patients (odds ratio: 0.25; 95% confidence interval: 0.09-0.72; P = 0.01), patients with urinary catheter (0.19; 0.04-0.89; P = 0.03) and hospitalization in single room (0.3; 0.15-0.6; P < 0.001).Conclusion: This study was conducted in a non-outbreak situation and showed a low rate of environmental contamination with pathogenic bacteria. Only 11% of environmental samples grew with >2.5 cfu/cm2, and they were related to non-pathogenic bacteria. No risk factors associated with environmental contamination were identified. [ABSTRACT FROM AUTHOR]

Purines are required for fundamental biological processes and alterations in their metabolism lead to severe genetic diseases associated with developmental defects whose etiology remains unclear. Here, we studied the developmental requirements for purine metabolism using the amphibian Xenopus laevis as a vertebrate model. We provide the first functional characterization of purine pathway genes and show that these genes are mainly expressed in nervous and muscular embryonic tissues. Morphants were generated to decipher the functions of these genes, with a focus on the adenylosuccinate lyase ( ADSL ), which is an enzyme required for both salvage and de novo purine pathways. adsl.L knockdown led to a severe reduction in the expression of the myogenic regulatory factors (MRFs: Myod1, Myf5 and Myogenin), thus resulting in defects in somite formation and, at later stages, the development and/or migration of both craniofacial and hypaxial muscle progenitors. The reduced expressions of hprt1.L and ppat , which are two genes specific to the salvage and de novo pathways, respectively, resulted in similar alterations. In conclusion, our data show for the first time that de novo and recycling purine pathways are essential for myogenesis and highlight new mechanisms in the regulation of MRF gene expression.

The pentose phosphate pathway (PPP) is critical for anabolism and biomass production. Here we show that the essential function of PPP in yeast is the synthesis of phosphoribosyl pyrophosphate (PRPP) catalyzed by PRPP-synthetase. Using combinations of yeast mutants, we found that a mildly decreased synthesis of PRPP affects biomass production, resulting in reduced cell size, while a more severe decrease ends up affecting yeast doubling time. We establish that it is PRPP itself that is limiting in invalid PRPP-synthetase mutants and that the resulting metabolic and growth defect can be bypassed by proper supplementation of the medium with ribose-containing precursors or by the expression of bacterial or human PRPP-synthetase. In addition, using documented pathologic human hyperactive forms of PRPP-synthetase, we show that intracellular PRPP as well as its derived products can be increased in both human and yeast cells, and we describe the ensuing metabolic and physiological consequences. Finally, we found that PRPP consumption appears to take place "on demand" by the various PRPP-utilizing pathways, as shown by blocking or increasing the flux in specific PRPP-consuming metabolic routes. Overall, our work reveals important similarities between human and yeast for both synthesis and consumption of PRPP., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the content of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Because metabolism is a complex balanced process involving multiple enzymes, understanding how organisms compensate for transient or permanent metabolic imbalance is a challenging task that can be more easily achieved in simpler unicellular organisms. The metabolic balance results not only from the combination of individual enzymatic properties, regulation of enzyme abundance, but also from the architecture of the metabolic network offering multiple interconversion alternatives. Although metabolic networks are generally highly resilient to perturbations, metabolic imbalance resulting from enzymatic defect and specific environmental conditions can be designed experimentally and studied. Starting with a double amd1 aah1 mutant that severely and conditionally affects yeast growth, we carefully characterized the metabolic shuffle associated with this defect. We established that the GTP decrease resulting in an adenylic/guanylic nucleotide imbalance was responsible for the growth defect. Identification of several gene dosage suppressors revealed that TAT1, encoding an amino acid transporter, is a robust suppressor of the amd1 aah1 growth defect. We show that TAT1 suppression occurs through replenishment of the GTP pool in a process requiring the histidine biosynthesis pathway. Importantly, we establish that a tat1 mutant exhibits synthetic sickness when combined with an amd1 mutant and that both components of this synthetic phenotype can be suppressed by specific gene dosage suppressors. Together our data point to a strong phenotypic connection between amino acid uptake and GTP synthesis, a connection that could open perspectives for future treatment of related human defects, previously reported as etiologically highly conserved.

The reversible adenine phosphoribosyltransferase enzyme (APRT) is essential for purine homeostasis in prokaryotes and eukaryotes. In humans, APRT (hAPRT) is the only enzyme known to produce AMP in cells from dietary adenine. APRT can also process adenine analogs, which are involved in plant development or neuronal homeostasis. However, the molecular mechanism underlying substrate specificity of APRT and catalysis in both directions of the reaction remains poorly understood. Here we present the crystal structures of hAPRT complexed to three cellular nucleotide analogs (hypoxanthine, IMP, and GMP) that we compare with the phosphate-bound enzyme. We established that binding to hAPRT is substrate shape-specific in the forward reaction, whereas it is base-specific in the reverse reaction. Furthermore, a quantum mechanics/molecular mechanics (QM/MM) analysis suggests that the forward reaction is mainly a nucleophilic substitution of type 2 (S N 2) with a mix of S N 1-type molecular mechanism. Based on our structural analysis, a magnesium-assisted S N 2-type mechanism would be involved in the reverse reaction. These results provide a framework for understanding the molecular mechanism and substrate discrimination in both directions by APRTs. This knowledge can play an instrumental role in the design of inhibitors, such as antiparasitic agents, or adenine-based substrates., (© 2019 Ozeir et al.)

Purine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized de novo , reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Although thoroughly characterized in microorganisms, such as yeast or bacteria, little is known about regulation of the purine biosynthesis network in metazoans. In humans, several diseases are linked to purine metabolism through as yet poorly understood etiologies. Particularly, the deficiency in adenylosuccinate lyase (ADSL)-an enzyme involved both in the purine de novo and recycling pathways-causes severe muscular and neuronal symptoms. In order to address the mechanisms underlying this deficiency, we established Caenorhabditis elegans as a metazoan model organism to study purine metabolism, while focusing on ADSL. We show that the purine biosynthesis network is functionally conserved in C. elegans Moreover, adsl-1 (the gene encoding ADSL in C. elegans ) is required for developmental timing, germline stem cell maintenance and muscle integrity. Importantly, these traits are not affected when solely the de novo pathway is abolished, and we present evidence that germline maintenance is linked specifically to ADSL activity in the recycling pathway. Hence, our results allow developmental and tissue specific phenotypes to be ascribed to separable steps of the purine metabolic network in an animal model., (Copyright © 2019 by the Genetics Society of America.)

Metabolism is a highly integrated process resulting in energy and biomass production. While individual metabolic routes are well characterized, the mechanisms ensuring crosstalk between pathways are poorly described, although they are crucial for homeostasis. Here, we establish a co-regulation of purine and pyridine metabolism in response to external adenine through two separable mechanisms. First, adenine depletion promotes transcriptional upregulation of the de novo NAD + biosynthesis genes by a mechanism requiring the key-purine intermediates ZMP/SZMP and the Bas1/Pho2 transcription factors. Second, adenine supplementation favors the pyridine salvage route resulting in an ATP-dependent increase of intracellular NAD + . This control operates at the level of the nicotinic acid mononucleotide adenylyl-transferase Nma1 and can be bypassed by overexpressing this enzyme. Therefore, in yeast, pyridine metabolism is under the dual control of ZMP/SZMP and ATP, revealing a much wider regulatory role for these intermediate metabolites in an integrated biosynthesis network., Competing Interests: BP, JC, CS, BD No competing interests declared, (© 2019, Pinson et al.)

5-Aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR, or acadesine) is a precursor of the monophosphate derivative 5-amino-4-imidazole carboxamide ribonucleoside 5'-phosphate (ZMP), an intermediate in de novo purine biosynthesis. AICAR proved to have promising anti-proliferative properties, although the molecular basis of its toxicity is poorly understood. To exert cytotoxicity, AICAR needs to be metabolized, but the AICAR-derived toxic metabolite was not identified. Here, we show that ZMP is the major toxic derivative of AICAR in yeast and establish that its metabolization to succinyl-ZMP, ZDP, or ZTP (di- and triphosphate derivatives of AICAR) strongly reduced its toxicity. Affinity chromatography identified 74 ZMP-binding proteins, including 41 that were found neither as AMP nor as AICAR or succinyl-ZMP binders. Overexpression of karyopherin-β Kap123, one of the ZMP-specific binders, partially rescued AICAR toxicity. Quantitative proteomic analyses revealed 57 proteins significantly less abundant on nuclei-enriched fractions from AICAR-fed cells, this effect being compensated by overexpression of KAP123 for 15 of them. These results reveal nuclear protein trafficking as a function affected by AICAR., (© 2019 Douillet et al.)

AICAR is the precursor of ZMP, a metabolite with antiproliferative properties in yeast and human. We aim at understanding how AICAR (and its active form ZMP) affects essential cellular processes. In this work, we found that ZMP accumulation is synthetic lethal with a hypomorphic allele of the ubiquitin-activating enzyme Uba1. A search for gene-dosage suppressors revealed that ubiquitin overexpression was sufficient to restore growth of the uba1 mutant upon AICAR treatment, suggesting that the ubiquitin pool is critical for cells to cope with AICAR. Accordingly, two mutants with constitutive low ubiquitin, ubp6 and doa1, were highly sensitive to AICAR, a phenotype that could be suppressed by ubiquitin overexpression. We established, by genetic means, that these new AICAR-sensitive mutants act in a different pathway from the rad6/bre1 mutants which were previously reported as sensitive to AICAR (Albrecht et al., Genetics 204:1447-1460, 2016). Two ubiquitin-conjugating enzymes (Ubc4 and Cdc34) and a ubiquitin ligase (Cdc4) were found to contribute to the ability of cells to cope with ZMP. This study illustrates the complexity of chemo-genetic interactions and shows how genetic analyses allow deciphering the implicated pathways, the individual gene effects, and their combined phenotypic contribution. Based on additivity and suppression patterns, we conclude that AICAR treatment shows synthetic interactions with distinct branches of the yeast ubiquitin pathway.

In natural tissues, the nutrition of cells and removal of waste products is facilitated by a dense capillary network which is generated during development. This perfusion system is also indispensable for tissue formation in vitro. Nutrition depending solely on diffusion is not sufficient to generate tissues of clinically relevant dimensions, which is a core aim in tissue engineering research. In this study, the establishment of a vascular network was investigated in a self-assembling approach employing endothelial and mural cells. The process of vascularization was analyzed in constructs based on a carrier matrix of decellularized porcine small intestinal submucosa (SIS). A three-dimensional hydrogel containing Matrigel™, collagen, and respective cells was casted on top of the SIS. Various types of human endothelial cells (hECs), e.g. HUVECs, cardiac tissue ECs (hCECs), pulmonary artery ECs (hPAECs), and iPSC-derived ECs, were co-cultured with human adipose tissue-derived stromal cells (hASCs) within the hydrogel. Analyzed hECs were able to self-assemble and form three-dimensional networks harboring small caliber lumens within the hydrogel constructs in the presence of hASCs as supporting cells. Additionally, microvessel assembling required exogenous growth factor supplementation. This study demonstrates the development of stable vascularized hydrogels applying hASCs as mural cells in combination with various types of hECs, paving the way for the generation of clinically applicable tissue engineered constructs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Phosphoribosyltransferases catalyze the displacement of a PRPP α-1'-pyrophosphate to a nitrogen-containing nucleobase. How they control the balance of substrates/products binding and activities is poorly understood. Here, we investigated the human adenine phosphoribosyltransferase (hAPRT) that produces AMP in the purine salvage pathway. We show that a single oxygen atom from the Tyr105 side chain is responsible for selecting the active conformation of the 12 amino acid long catalytic loop. Using in vitro, cellular, and in crystallo approaches, we demonstrated that Tyr105 is key for the fine-tuning of the kinetic activity efficiencies of the forward and reverse reactions. Together, our results reveal an evolutionary pressure on the strictly conserved Tyr105 and on the dynamic motion of the flexible loop in phosphoribosyltransferases that is essential for purine biosynthesis in cells. These data also provide the framework for designing novel adenine derivatives that could modulate, through hAPRT, diseases-involved cellular pathways., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Previous genetic analyses showed phenotypic interactions between 5-amino-4-imidazole carboxamide ribonucleotide 5'-phosphate (AICAR) produced from the purine and histidine pathways and methionine biosynthesis. Here, we revisited the effect of AICAR on methionine requirement due to AICAR accumulation in the presence of the fau1 mutation invalidating folinic acid remobilization. We found that this methionine auxotrophy could be suppressed by overexpression of the methionine synthase Met6 or by deletion of the serine hydroxymethyltransferase gene SHM2. We propose that in a fau1 background, AICAR, by stimulating the transcriptional expression of SHM2, leads to a folinic acid accumulation inhibiting methionine synthesis by Met6. In addition, we uncovered a new methionine auxotrophy for the ade3 bas1 double mutant that can be rescued by overexpressing the SHM2 gene. We propose that methionine auxotrophy in this mutant is the result of a competition for 5,10-methylenetetrahydrofolate between methionine and deoxythymidine monophosphate synthesis. Altogether, our data show intricate genetic interactions between one-carbon units, purine and methionine metabolism through fine-tuning of serine hydroxymethyltransferase by AICAR and the transcription factor Bas1.

5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAr) is the precursor of the active monophosphate form (AICAR), a small molecule with potent anti-proliferative and low energy mimetic properties. The molecular bases for AICAR toxicity at the cellular level are poorly understood. Here, we report the isolation and characterization of several yeast AICAr-hypersensitive mutants. Identification of the cognate genes allowed us to establish that thiamine transporters Thi7 and Thi72 can efficiently take up AICAr under conditions where they are overexpressed. We establish that, under standard growth conditions, Nrt1, the nicotinamide riboside carrier, is the major AICAr transporter in yeast. A study of AICAR accumulation in human cells revealed substantial disparities among cell lines and confirmed that AICAr enters cells via purine nucleoside transporters. Together, our results point to significant differences between yeast and human cells for both AICAr uptake and AICAR accumulation., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

5-Amino-4-imidazolecarboxamide ribonucleotide 5'-phosphate (AICAR) is a monophosphate metabolic intermediate of the de novo purine synthesis pathway that has highly promising metabolic and antiproliferative properties. Yeast mutants unable to metabolize AICAR are auxotroph for histidine. A screening for suppressors of this phenotype identified recessive and dominant mutants that result in lowering the intracellular AICAR concentration. The recessive mutants affect the adenosine kinase, which is shown here to catalyze the phosphorylation of AICAR riboside in yeast. The dominant mutants strongly enhance the capacity of the alkaline phosphatase Pho13 to dephosphorylate 5-amino-4-imidazole N-succinocarboxamide ribonucleotide 5'-phosphate(SAICAR) into its non-toxic riboside form. By combining these mutants with transcriptomics and metabolomics analyses, we establish that in yeast responses to AICAR and SAICAR are clearly linked to the concentration of the monophosphate forms, whereas the derived nucleoside moieties have no effect even at high intracellular concentration. Finally, we show that AICAR/SAICAR concentrations vary under physiological conditions known to modulate transcription of the purine and phosphate pathway genes.

Coordinating homeostasis of multiple metabolites is a major task for living organisms, and complex interconversion pathways contribute to achieving the proper balance of metabolites. AMP deaminase (AMPD) is such an interconversion enzyme that allows IMP synthesis from AMP. In this article, we show that, under specific conditions, lack of AMPD activity impairs growth. Under these conditions, we found that the intracellular guanylic nucleotide pool was severely affected. In vivo studies of two AMPD homologs, Yjl070p and Ybr284p, indicate that these proteins have no detectable AMP, adenosine, or adenine deaminase activity; we show that overexpression of YJL070c instead mimics a loss of AMPD function. Expression of the yeast transcriptome was monitored in a AMPD-deficient mutant in a strain overexpressing YJL070c and in cells treated with the immunosuppressive drug mycophenolic acid, three conditions that lead to severe depletion of the guanylic nucleotide pool. These three conditions resulted in the up- or downregulation of multiple transcripts, 244 of which are common to at least two conditions and 71 to all three conditions. These transcriptome results, combined with specific mutant analysis, point to threonine metabolism as exquisitely sensitive to the purine nucleotide balance.

Purine salvage is a complex pathway allowing a correct balance between adenylic and guanylic derivatives. In this paper, we show that GUD1 (YDL238c) encodes guanine deaminase, a catabolic enzyme producing xanthine and ammonia from guanine. Importantly, Gud1p activity was higher during post-diauxic growth, suggesting that a decrease of the guanylic nucleotide pool could be required when cells shift from proliferation to quiescence.

Background: The purine salvage enzyme inosine 5'-monophosphate (IMP)-specific 5'-nucleotidase catalyzes degradation of IMP to inosine. Although this enzymatic activity has been purified and characterized in Saccharomyces cerevisiae, the gene encoding IMP 5'-nucleotidase had not been identified., Results: Mass spectrometry analysis of several peptides of this enzyme purified from yeast allowed identification of the corresponding gene as YOR155c, an open reading frame of unknown function, renamed ISN1. The deduced Isn1p sequence was clearly not homologous to 5'-nucleotidases from other species. However, significant similarities to Isn1p were found in proteins of unknown function from Neurospora crassa, Plasmodium falciparum and several yeast species. Knock-out of ISN1 resulted in the total loss of IMP-specific 5'-nucleotidase activity, thus confirming that the ISN1 gene indeed encodes the enzymatic activity purified from yeast. In vivo studies revealed that, when IMP is overproduced through constitutive activation of the IMP de novo synthesis pathway, ISN1 is required for excretion of inosine and hypoxanthine in the medium., Conclusion: We have identified a new yeast gene, ISN1 (YOR155c), as encoding IMP-specific 5'-nucleotidase activity. The ISN1 gene defines a new type of 5'-nucleotidase which was demonstrated to be functional in vivo.

The immunosuppressive drug mycophenolic acid (MPA) is a potent and specific inhibitor of IMP dehydrogenase, the first committed step of GMP synthesis. A screen for yeast genes affecting MPA sensitivity, when overexpressed, allowed us to identify two genes, IMD2 and TPO1, encoding a homologue of IMP dehydrogenase and a vacuolar pump, respectively. In parallel, 4787 yeast strains, each carrying an identified knock-out mutation, were tested for growth in the presence of MPA, allowing identification of 100 new genes affecting MPA resistance when disrupted. Disturbance of several cellular processes, such as ergosterol biosynthesis, vacuole biogenesis, or glycosylation impaired the natural capacity of yeast to resist MPA, although most of the highly sensitive mutants affected the transcription machinery (19 mutants). Expression of TPO1 and/or IMD2 was strongly affected in 16 such transcription mutants suggesting that low expression of these genes could contribute to MPA sensitivity. Interestingly, the spt3, spt8, and spt20 mutants behaved differently than other Spt-Ada-Gcn5-acetyltransferase (SAGA) mutants. Indeed, in these three mutants, as in previously characterized transcription elongation mutants, IMD2 expression was only affected in the presence of MPA, thus suggesting a possible role for some SAGA subunits in transcription elongation.

We determined the number of single and double strand breaks (ssb and dsb) in a DNA-chloroterpyridine platinum complex induced by resonant photoabsorption in the L(III) innershell of a platinum atom. The number of ssb and dsb were measured in supercoiled plasmids (AG30) versus the chloroterpyridine platinum concentration, i.e., the ratio of intercalated molecules to the number of phosphate sites in DNA. A significant increase in the number of ssb and dsb was observed when the DNA contained intercalated molecules. This technique is an efficient way to induce ssb and dsb triggered by the atomic Auger effect.

Single-strand breaks (SSBs) and double-strand breaks (DSBs) induced in DNA under phosphorus K-shell resonant absorption have been studied using supercoiled plasmids. The kinetics of the production of SSBs and DSBs exhibits a linear and a quadratic dependence, respectively, on photon fluence. Cross sections and quantum yields have been measured. The resonant photoexcitation of the phosphorus atoms was found to increase the DSB/SSB ratio compared to the off-resonance excitation. This enhancement factor can be related to the measured enhancement of the rate of cellular death and gene mutation in yeast under similar experimental conditions reported previously in the literature. Such resonant excitation of a specific atom belonging to DNA turns out to be an elegant method to investigate pure direct effects.

The present study uses three techniques of autotransfusion in heart surgery under ECC: peroperative and post-ECC transfusion of blood removed after induction of anaesthesia (group I: 25 patients); postoperative transfusion of extravasated thoracic blood (group II: 24 patients) and a combination of the two (group III: 25 patients). Postoperative bleeding was comparable in all groups; A subset likely to haemorrhage made up of patients who had lost more than one litre of blood was isolated and demonstrated a reduction in the number of homologous red cell concentrates needed for the autotransfused population in comparison with the controls (2.4 +/- 2.6 vs 5.7 +/- 3.5 red cell concentrates, p less than 0.05) and was particularly marked in Group II patients who received 1.9 +/- 2.2 homologous red cell concentrates. None of the techniques caused any side-effects. Combination of the two autotransfusion techniques in heart surgery does not secure any additional advantages compared with postoperative autotransfusion alone.

The aim of this study was to investigate direct cytotoxicity to human and rat hepatocytes in primary culture from halothane and compare it with that of isoflurane, which is known to be minimally metabolized and less toxic in vivo. Both human and rat parenchymal cells were isolated by the two-step collagenase perfusion method and after attachment to plastic were incubated with either volatile anesthetic for 24 h. All the cultures were maintained in 20% O2 condition and were not induced prior to anesthetic treatment. Temperature, atmosphere conditions, and anesthetic concentrations were kept constant during the study period. Evaluation of cytotoxicity was based on morphologic, biologic (determination of both extracellular and intracellular lactate dehydrogenase activity), and metabolic (protein synthesis and secretion) end points. Protein synthesis and secretion rates were found to be the most sensitive parameters in hepatocyte cultures from both species. Protein synthesis was inhibited by 18% and protein secretion by 50% in the presence of 1 and 1.25 mM halothane, respectively, in human cell cultures (P less than 0.05). With 1.25 mM halothane intracellular lactate dehydrogenase was also decreased; lactate dehydrogenase leakage and morphologic alterations were detected only beyond 5 mM halothane. By contrast, in rat hepatocyte cultures protein secretion was inhibited by 26% and protein synthesis by 20% in the presence of 0.1 and 0.75 mM halothane, respectively, whereas morphologic alterations and a 37% lactate dehydrogenase leakage increase were observed with the concentration of 1 mM (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A 30-year-old woman underwent a liver transplantation for metastasis of a carcinoid tumor of the midgut previously resected. Operative manipulation of the liver resulted in arterial hypotension, tachycardia, high pulmonary arterial pressure, oedema of the face and peripheral cyanosis, although the patient was given somatostatin (Modustatine, Clin-Midy) (300 micrograms a hour) prior to the procedure. The improvement of the symptoms was obtained by the increase of somatostatin infusion rate to 750 micrograms a hour associated with dopamine (6 micrograms.kg-1.min-1) and fluid replacement. The diagnosis of carcinoid syndrome is discussed. This unusual observation stresses the difficulty in preventing and/or treating a carcinoid shock. If somatostatin seems to be the treatment of choice of such a syndrome, its role in that case was limited.

Propofol was assessed for eye surgery in 20 children. ASA group I or II, 2-14 year-old, randomly assigned to 2 equal groups. Premedication, analgesia and muscle paralysis were similar in both groups. Group P patients were given an induction dose of 4 mg.kg-1 propofol, followed by an infusion of 15 mg.kg-1.h-1 for the first half hour, and then 10 mg.kg-1.h-1 to maintain anaesthesia. Group C patients were given 10 mg.kg-1 thiopentone for induction and halothane for maintenance. The quality of anaesthesia was assessed by monitoring adverse effects, heart rate, blood pressure, the length of anaesthesia, the delay of the first spontaneous breath and eye opening, and extubation. Intraocular pressure was measured before and 3 min after intubation, and 5 min after extubation. The quality of anaesthetic induction and maintenance were very similar in both groups. Pain occurred more frequently at the injection site with propofol (p less than 0.01). Children in group P recovered more quickly, and extubation was possible much earlier in this group (p less than 0.05). However, restlessness was significantly more frequent in group P (n = 9) than in group C (n = 1) (p less than 0.01). Systolic, diastolic blood pressure and heart rate were significantly lower in group P (p less than 0.05; 0.001; 0.001 respectively). No significant decrease in intraocular pressure in both groups was observed. The use of propofol for eye surgery in children is acceptable, despite some restlessness during recovery.

38 cases of chemionucleolysis, under neuroleptanalgesia by droperidol-Fentanyl with spontaneous respiration are reported. This technique was satisfactory and allowed the patient to cooperate.

The association of bupivacaine and fentanyl appeared as the best method of inducing satisfactory obstetrical analgesia. But the various techniques of drug administration had to be detailed; this justified the present work, a single-blind controlled trial performed on 159 primipara women at term (except one of them), randomized in four groups, after informed consent. In each group, the number of patients, the age and the degree of uterine dilatation at the beginning of the epidural anaesthesia were comparable. Epidural anaesthesia aimed to improve the maternal comfort during labour. After a first epidural injection of 10 ml, several other injections of 6 ml were carried out according to four different protocols (I, II, III, IV), with different concentrations of fentanyl (respectively 0, 0.05, 0.1 and 0.15 mg). The mean total dosages of fentanyl were statistically higher in the protocols III and IV. The foetal cardiac rhythm and uterine contractions were monitored continuously as well as maternal blood pressure and heart beats during labour. The following parameters were assessed: contraction pain intensity (five point scale), the onset of analgesia, the duration of analgesia, the length of labour, the interval between the first drug injection and subsequent injections, the type of delivery. In the newborn, Apgar score was assessed at 1, 5 and 10 min after delivery. The degree of analgesia was statistically improved in the groups receiving fentanyl, without any differences between them. On the other hand, the length of labour was shorter with protocol II (lowest concentration of fentanyl).(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective study of 54 torsades de pointe cases in a cardiology department enabled us to specify the main characteristics of this serious arrythmia often observed in intensive care units: --the diagnostic criteria: more than the pattern of tachycardia attack, late ventricular premature beats and particularly QT prolongation are necessary for proper diagnosis. These two criteria allow us to differentiate between torsades de pointe and multiform ventricular tachycardia with similar morphology especially in acute myocardial ischaemia; --their clinical repercussion: the shortness of circulatory arrest related to the spontaneous end of the arrythmia explains that the torsades de pointe often result in short faintings. Nevertheless, they may degenerate into ventricular fibrillation (17 p. 100) which, in cases of recurrence, induced four deaths in this study; --there are many possible aetiologies often associated (30 p. 100) in the same patient. Their research must be exhaustive in each case. The chronic bradycardias especially the atrioventricular blocks of two or three degree whether continuous or not are often responsible (57 p. 100). Then, the metabolic disorders, essentially hypokalaemia and constant drug administration (antiarrythmic agents belonging to group I of Vaughan William's classification, some antianginal drugs, vasodilatator drugs) are often chief causative agents. Other aetiologies are rare. In 9 p. 100 of cases, no aetiological factor is found; --the best treatment is to suppress aetiological factors, to stop the administration of antiarrhythmic drugs; torsades de pointe must be controlled by increasing the heart rate; pace maker stimulation is the best way of making QT shorter and thus of synchronizing ventricular depolarization.

Spontaneous uterine rupture at term during labor of a non-scarred uterus under epidural anaesthesia is reported in a 17-yr-old primigravida. This exceptional event may lead to catastrophic maternal and fetal consequences. The authors discuss the prevention and diagnosis of this obstetrical complication.

Must often reporting to an hepatic subcapsular hemorrhage with pre or true eclampsia, Spontaneous rupture of adenoma of the liver during pregnancy is unusual entity. Very exceptionally cases of rupture of anatomic hepatic lesion underlying had been reported. About a new case, diagnosis, physiopathologic and management problems are approached.

Pneumatocele and haemato-pneumatocele are air or air/fluid cavitary lesions which develop in the lung parenchyma after thoracic trauma. The formation of this lesion requires a direct violent impact on the pliable lung wall which explains its frequency in young adults. They are preferentially localised in the lung bases. The importance of associated lesions often marks the pneumatocele. Though rarely described, its frequency is certainly underestimated. If haemoptysis is the most frequent clinical sign it is the chest x-ray which demonstrates the early abnormality in the form of a rounded translucent image with a fine contour and variable diameter. The existence of a fluid level suggests the presence of blood (haemato-pneumatocele). The differential diagnosis with a localised pneumothorax, a diaphragmatic hernia and a pre-existing cystic lesion is easy as a rule but an evacuated pulmonary haematoma may lead to the discussion, especially as the mechanism of their formation may be the same. In isolation their clinical implications are minimal, their evolution favourable and after several weeks with a restitution of the integrity of the pulmonary parenchyma the absence of therapeutic intervention is justified.