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Biomedical subjects

A Robert

Publications and source records attributed to A Robert.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pulsatile electrical impedance response from cerebrally dead adult patients is not a reliable tool for detecting cerebral perfusion changes.

The original objective of this work was to verify the possibility of using electrical pulsatile cerebral impedance measurements as a diagnostic aid for assessing the brain-death condition in adults; a subordinate target was to validate a simple method for detecting perfusional changes in the brain. To this end, impedance signals were recorded, for a comparative study, from both live subjects and brain-dead patients, using a simple four-electrode arrangement. Rather unexpectedly, pulsatile transcephalic impedance waveforms exhibiting a temporal dependance similar to those of live subjects were detected in artificially ventilated, cerebrally dead, adult subjects; distributions of the time delays between impedance peaks and ECG peaks were also recorded for the two groups (dead and live subjects). These data provided no evidence, at the 1% significance level, against the hypothesis that the two sample groups are drawn from identical populations. The detection of impedance variations from brain-dead patients can be explained by the residual persistence of blood flow through the scalp, by mechanical variations synchronous with the heart beat and by the presence of the oscillating flow and the systolic spikes that precede the final blood flow arrest. The fact that impedance variations can be traced back to a multiplicity of causes, unrelated to the normal unidirectional flow, renders the transcephalic impedance method inappropriate for detecting cerebral perfusion changes in adults. This conclusion is also strengthened by some theoretical results recently derived from a multilayer model of the head.

Adult↗
PubMed2001

The clinical relevance of the citrate effect on International Normalized Ratio determinations depends on the reagent and instrument combination used.

Multiple studies have shown that the two different citrate concentrations in common use as the anticoagulant in blood collection for haemostasis assays can affect the results obtained with the prothrombin time assay. It is clear from the literature that there is considerable variability in the results obtained using different instrument-reagents combinations, but the clinical relevance of these differences is unclear. Most of the studies have used an optical system for end-point detection. This study reports on the citrate sensitivity using mechanical end-point detection. Using two different reagents, one previously shown to be citrate sensitive on optical systems (Neoplastin CI plus) and a citrate-insensitive reagent (Neoplastin CI), we demonstrate that the effect of using different citrate concentrations (0.105 or 0.129 mol/l) has statistically significant but clinically irrelevant effects on the International Normalized Ratio using a mechanical instrument (STA)-reagent combination (mean percentage difference in results, 1.9 and 3.8% respectively). This demonstrates that the citrate effect is both instrument type and reagent dependent. Every reagent and instrument combination needs to be tested to see whether any citrate effect exists. In a secondary study, it was shown that the international reference rabbit thromboplastin (CRM 149(s)) was not citrate-concentration sensitive.

Animals↗
PubMed2001

Early acenocoumarol overanticoagulation among cytochrome P450 2C9 poor metabolizers.

Cytochrome P450 2C9 (CYP2C9) is the enzyme that terminates the anticoagulant effect of warfarin. The heterozygous carriers of the two allelic variants CYP2C9*2 and CYP2C9*3 have been associated with impaired warfarin metabolism and a higher risk of haemorrhage. Only three CYP2C9 poor metabolizers (CYP2C9*3/CYP2C9*3) initiating warfarin treatment have so far been identified, all of them with a dramatic overdose occurring a few days after treatment initiation. Acenocoumarol, another coumarinic anticoagulant, has recently been shown to be metabolized by CYP2C9. We report, for the first time, two cases of dramatic overanticoagulation occurring in patients starting acenocoumarol treatment while taking recommended doses (4 mg/day). In both cases, the overdose was discovered at the first INR control with values above 9. Genotyping revealed that the two patients were homozygous for the CYP2C9*3 allele. Our report highlights the need for CYP2C9 genotyping before starting oral anticoagulants in order to prevent early overanticoagulation episodes.

Acenocoumarol↗
PubMed2001

Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriage.

OBJECTIVE: To determine whether there is an association between early recurrent miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A prothrombin mutations. DESIGN: A prospective study. SETTING: Department of Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France. POPULATION: Two groups of women: those with early unexplained recurrent miscarriage before 10 weeks of pregnancy (n = 260) and control healthy women without a previous history of thromboembolism (n = 240). METHODS: Screening for defects in the protein C anticoagulant pathway was performed using the anticoagulant response to agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation testing was performed for each low ACV level. Each sample was tested for the G20210A prothrombin mutation. RESULTS: Factor V Leiden and G20210A mutations were found to be associated with early recurrent spontaneous miscarriage before 10 weeks of pregnancy, the odds ratios being 2.4 (95% CI 1-5) and 2.7 (95% CI 1-7), respectively. Similar results were found whether or not women had had a previous live birth. CONCLUSIONS: Early recurrent miscarriage before 10 weeks of pregnancy is significantly associated with Factor V or G20210A prothrombin mutations. These results indicate a possible role for anticoagulant prevention in these early miscarriages.

Abortion, Habitual↗
PubMed2001

In vitro activities of DU-1102, a new trioxaquine derivative, against Plasmodium falciparum isolates.

The antimalarial trioxaquine derivative DU-1102, synthesized by covalent linkage between aminoquinoline and trioxane moieties, was highly active against Cameroonian isolates (mean 50% inhibitory concentration of 43 nmol/liter) of Plasmodium falciparum. There was no correlation between the responses to DU-1102 and chloroquine and only a low correlation between the responses to DU-1102 and pyrimethamine, suggesting an independent mode of action of the trioxaquine against the parasites.

Aminoquinolines↗
PubMed2000

Tetralogy of Fallot: transannular and right ventricular patching equally affect late functional status.

BACKGROUND: In tetralogy of Fallot, transannular patching is suspected to be responsible for late right ventricular dilatation. METHODS AND RESULTS: In our institution, 191 patients survived a tetralogy of Fallot repair between 1964 and 1984. Transannular patching was used in 99 patients (52%), patch closure of a right ventriculotomy in 35, and direct closure of a right ventriculotomy in 55. Two had a transatrial-transpulmonary approach. To identify predictive factors of adverse long-term outcome related to right ventricular dilatation, the following events were investigated: cardiac death, reoperation for symptomatic right ventricular dilatation, and NYHA class II or III by Cox regression analysis. Mean follow-up reached 22+/-5 years. The 30-year survival was 86+/-5%. Right ventricular patching, whether transannular or not, was the most significant independent predictor of late adverse event (improvement chi(2)=16.6, P:<0.001). In patients who had direct closure, the ratio between end-diastolic right and left ventricular dimensions on echocardiography was smaller (0.61+/-0.017 versus 0. 75+/-0.23, P:=0.007), with a smaller proportion presenting severe pulmonary insufficiency (9% versus 40%, P:=0.005). There was no difference between right ventricular and transannular patching concerning late outcome (log rank P: value=0.6), right ventricular size (0.70+/-0.28 versus 0.76+/-0.26, P:=0.4), or incidence of severe pulmonary insufficiency (30% versus 43%, P:=0.3). CONCLUSIONS: In tetralogy of Fallot, transannular patching does not result in a worse late functional outcome than patching of an incision limited to the right ventricle. Both are responsible for a similar degree of long-term pulmonary insufficiency and right ventricular dilatation.

Adolescent↗
PubMed2000

Insect immunity. Constitutive expression of a cysteine-rich antifungal and a linear antibacterial peptide in a termite insect.

Two novel antimicrobial peptides, which we propose to name termicin and spinigerin, have been isolated from the fungus-growing termite Pseudacanthotermes spiniger (heterometabole insect, Isoptera). Termicin is a 36-amino acid residue antifungal peptide, with six cysteines arranged in a disulfide array similar to that of insect defensins. In contrast to most insect defensins, termicin is C-terminally amidated. Spinigerin consists of 25 amino acids and is devoid of cysteines. It is active against bacteria and fungi. Termicin and spinigerin show no obvious sequence similarities with other peptides. Termicin is constitutively present in hemocyte granules and in salivary glands. The presence of termicin and spinigerin in unchallenged termites contrasts with observations in evolutionary recent insects or insects undergoing complete metamorphosis, in which antimicrobial peptides are induced in the fat body and released into the hemolymph after septic injury.

Amino Acid Sequence↗
PubMed2000

Adenovirus E4 open reading frame 4-induced apoptosis involves dysregulation of Src family kinases.

The adenoviral early region 4 open reading frame 4 (E4orf4) death factor induces p53-independent apoptosis in many cell types and appears to kill selectively transformed cells. Here we show that expression of E4orf4 in transformed epithelial cells results in early caspase-independent membrane blebbing, associated with changes in the organization of focal adhesions and actin cytoskeleton. Evidence that E4orf4 can associate with and modulate Src family kinase activity, inhibiting Src-dependent phosphorylation of focal adhesion kinase (FAK) and paxillin while increasing phosphorylation of cortactin and some other cellular proteins, is presented. Furthermore, E4orf4 dramatically inhibited the ability of FAK and c-src to cooperate in induction of tyrosine phosphorylation of cellular substrates, suggesting that E4orf4 can interfere with the formation of a signaling complex at focal adhesion sites. Consistent with a functional role for E4orf4-Src interaction, overexpression of activated c-src dramatically potentiated E4orf4-induced membrane blebbing and apoptosis, whereas kinase dead c-src constructs inhibited E4orf4 effects on cell morphology and death. Moreover treatment of E4orf4-expressing cells with PP2, a selective Src kinase inhibitor, led to inhibition of E4orf4-dependent membrane blebbing and later to a marked decrease in E4orf4-induced nuclear condensation. Taken together, these observations indicate that expression of adenovirus 2 E4orf4 can initiate caspase-independent extranuclear manifestations of apoptosis through a modulation of Src family kinases and that these are involved in signaling E4orf4-dependent apoptosis. This study also suggests that Src family kinases are likely to play a role in the cytoplasmic execution of apoptotic programs.

Adenoviruses, Human↗
PubMed2000

Recombinant protein production driven by the tryptophan promoter is tightly controlled in ICONE 200, a new genetically engineered E. coli mutant.

Batch processes for recombinant gene expression in prokaryotic systems should optimally comprise a growth phase with minimal promoter activity followed by a short phase favoring expression. The strong promoter of the tryptophan operon (Ptrp) gives high-level expression of recombinant proteins in E. coli. The inefficiency to control basal expression before induction is however a major obstacle towards the use of Ptrp, especially in the case of toxic proteins. To circumvent this problem, a novel E. coli strain has been generated. This mutant, named ICONE 200 (Improved Cell for Over and Non-leaky Expression), underwent replacement of tnaA, the tryptophanase encoding gene, with the trpR gene encoding the aporepressor of Ptrp. Detailed analysis of ICONE 200 showed that tryptophan, in addition to its natural role of Ptrp co-repressor, was able to induce trpR through the tryptophan-inducible tryptophanase promoter/operator. Consequently, Ptrp-dependent expression was efficiently repressed in the presence of tryptophan and was turned on, as in wild-type E. coli, as soon as tryptophan was exhausted from the medium. ICONE 200 has the capacity to express a wide range of proteins including toxic proteins such as HIV-1 protease and poliovirus 2B protein. ICONE 200 is a new host carrying stable, targeted, and marker-free genetic modifications and a candidate for large-scale applications.

Bacterial Proteins↗
PubMed2000

Time course of functional recovery after coronary artery bypass graft surgery in patients with chronic left ventricular ischemic dysfunction.

Chronic left ventricular (LV) ischemic dysfunction, a condition often referred to as myocardial hibernation, is associated in humans with ultrastructural alterations of the myocytes, including the loss of myofilaments and the accumulation of glycogen. Given the severity of these structural changes, contractile function is unlikely to resume immediately upon revascularization. Therefore, the aim of the present study was to assess the time course of functional improvement after successful revascularization as well as its potential structural correlates. We studied 32 patients with coronary disease and chronic LV ischemic dysfunction who underwent bypass surgery. Dynamic positron emission tomography with N-13 ammonia and F-18 deoxyglucose to assess myocardial perfusion and glucose metabolism was performed in 29 patients. In all patients, a transmural biopsy was harvested from the center of the dysfunctional area, to quantify the increase in extracellular matrix and the presence of structurally altered cardiomyocytes. LV function was serially measured by digitized 2-dimensional echocardiography before and at 10 days, 2 months, and 6 months after revascularization. The time course of recovery of regional function was estimated from the monoexponential decrease in dysfunctional wall motion score. At follow-up, 19 patients had improved LV function, whereas 13 patients showed persistent dysfunction. Before revascularization, reversibly dysfunctional segments had higher myocardial blood flow (82 +/- 29 vs 53 +/- 21 ml. (min. 100 g)(-1), p = 0.044), higher glucose uptake (40 +/- 16 vs 21 +/- 9 micromol. (min. 100 g)(-1), p = 0.001), and less increase in extracellular matrix (25 +/- 15% vs 46 +/- 17%, p = 0.0008) than segments with persistent dysfunction. The extent to which function recovered was positively correlated with myocardial blood flow and negatively correlated with the increase in the extracellular matrix. In patients with reversible dysfunction, the return of segmental function was progressive and followed a monoexponential time course with a median time constant of 23 days (range 6 to 78). The rate of recovery correlated best with the proportion of altered cardiomyocytes in the biopsy. The present study thus indicates that the recovery of regional and global LV function after successful revascularization is progressive and follows a monoexponential time course that is influenced by the extent of the structural changes affecting cardiomyocytes.

Adult↗
PubMed2000

Partial protection to respiratory syncytial virus (RSV) elicited in mice by intranasal immunization using live staphylococci with surface-displayed RSV-peptides.

A live bacterial vaccine-delivery system based on the food-grade bacterium Staphylococcus carnosus was used for delivery of peptides from the G glycoprotein of human respiratory syncytial virus, subtype A (RSV-A). Three peptides, corresponding to the G protein amino acids, 144-159 (denoted G5), 190-203 (G9) and 171-188 (G4 S), the latter with four cysteine residues substituted for serines, were expressed by recombinant means as surface-exposed on three different bacteria, and their surface accessibility on the bacteria was verified by fluorescence-activated cell sorting (FACS). Intranasal immunization of mice with the live recombinant staphylococci elicited significant anti-peptide as well as anti-virus serum IgG responses of balanced IgG1/IgG2a isotype profiles, and upon viral challenge with 10(5) tissue culture infectious doses(50) (TCID(50)), lung protection was demonstrated for approximately half of the mice in the G9 and G4 S immunization groups. To our knowledge, this is the first study in which protective immunity to a viral pathogen has been evoked using food-grade bacteria as vaccine-delivery vehicles.

Administration, Intranasal↗
PubMed2000

Age-related arterial calcification in rats.

In man, i) arteries calcify with age and ii) age-linked arterial calcification is amplified by vascular pathology such as hypertension or arteriosclerosis. Age-linked arterial calcification has a bad prognosis but drugs to prevent it are lacking. This is partially due to the lack of appropriate animal models. This paper looks at the extent to which arteries calcify with age in the rat and whether hypertension or arteriosclerosis amplifies such calcification. Total calcium levels were determined by acid digestion and flame spectrophotometry and intracellular calcium levels ([Ca2+]i) by the intracellular calcium-sensitive dye, fura-2. Arteries contained up to 5 times more calcium than other soft tissues. Arteries progressively calcified with age whereas other soft tissues did not. Accumulation of calcium with age was essentially extracellular. Hypertension had no effect on age-related arterial calcification. Calcification of the same order as in man was produced in a rat model of arteriosclerosis (vitamin D plus nicotine treatment). In conclusion, as in man, age-linked, organ-specific arterial calcification does occur in rats but its intensity is far less. Arterial calcification of a similar degree to that observed in man can be obtained in rats by hypervitaminosis D plus nicotine.

Aging↗
PubMed2000

A reversible model of acute hepatic failure by temporary hepatic ischemia in the pig.

BACKGROUND: To evaluate new therapies for human fulminant hepatic failure, a suitable large animal model is needed. The purpose of this study was to develop a reversible surgical model of acute hepatic liver failure by transient ischemia in pigs. MATERIALS AND METHODS: Under general anesthesia, an end-to-side portacaval shunt was performed in 17 pigs and tape was laid around the hepatoduodenal ligament. Two days after construction of the functional portacaval shunt, 13 ambulant pigs underwent transient total liver ischemia by tightening of the tape around the hepatoduodenal ligament for 5.5 h. During ischemia, 10% glucose was continuously infused intravenously to prevent hypoglycemia. RESULTS: Ten animals (77%) died with hepatic coma after a mean duration of 22.5 +/- 1.9 h. The 3 remaining animals survived more than 5 days and were sacrificed. In dying animals, encephalopathy was observed 14 +/- 1.7 h after the onset of ischemia. During ischemia, similar progressive decrease of fibrinogen, platelets, prothrombin time, and factors V and VII activities was observed in dying and surviving animals. Just before death, mean prothrombin and factors V and VII activities were respectively 22 +/- 2, 21 +/- 4.4, and 24 +/- 5%. At 22 h, plasma ammonia and lactate levels were respectively 705 +/- 93 micromol/L and 10.5 +/- 0.4 mmol/L in dying animals and 249 +/- 75 micromol/L and 2.9 +/- 0.1 mmol/L in surviving animals (P < 0.01). Estimation of the percentage liver cells necrosed was 74 +/- 4.7% in the survivors and 86 +/- 5.5% in animals who died of hepatic coma (NS). CONCLUSIONS: This model is reproducible and reversible and should allow the quantitative evaluation of new technologies, such as bioartificial liver, for the support of hepatic failure in humans.

Acute Disease↗
PubMed2000

Perturbation in dystrophin-associated glycoprotein complex in a boy with Becker muscular dystrophy.

We report on a boy with a BMD phenotype presenting with a deletion of exons 45-49 in the DMD gene. Immunofluorescence and Western blot analysis of a skeletal muscle sample revealed, as expected, truncated dystrophin with loss in the central rod domain, but with an unusual severe deficiency in the sarcoglycan complex, as in severe DMD. We discuss possible neighboring between dystrophin and associated proteins within their complex organization at the muscle membrane.

Child, Preschool↗
PubMed2000

Relationship of sigma activity to sleep interictal epileptic discharges: a study in children affected by benign epilepsy with occipital paroxysms.

INTRODUCTION: By applying spectral analysis techniques we recently showed that Interictal Epileptic Discharges (IEDs) are modulated by sleep spindle synchronization mechanisms (sigma activity, SA, 12. 0-16.0 Hz). This finding applies to both benign epilepsy of childhood with rolandic spikes (BECRS), to symptomatic epilepsy of childhood strongly activated by sleep and to the Landau-Kleffner syndrome. These results are quite different from those found in adult partial epileptic patients where slow wave activity (SWA, 0. 5-4.5 Hz) plays the main role in the modulation of IEDs during sleep. This finding could suggest that the activation of IEDs by spindle activities could be an age-related feature of epilepsy. In order to verify this hypothesis we studied a group of epileptic children performing a polysomnographic study on five patients with BEOP strongly activated by sleep. METHODS: We performed overnight continuous EEG-polysomnographic studies in five patients (mean age 6. 0+/-2.5). The IEDs count was performed on the most active occipital lead. The temporal series of SWA and SA values, derived from spectral analysis, were obtained from a spike-free central, controlateral lead. Relationships between SA, SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significantly higher correlation between IEDs and SA with respect to SWA in all subjects, in total sleep time. When the analysis was limited only to NREM sleep the correlation between sigma and IEDs was even more impressive. CONCLUSIONS: Data suggest that also in BEOP the spindle generating mechanism modulates the IEDs during sleep. This mechanism seems to be an age-dependent phenomenon with no relation whatsoever either with the type of epilepsy or with the brain region.

Child↗
PubMed2000

[Palliative care in pediatric oncology].

Improving the management of dying children has always been a common desire among staff who take care of children with incurable life-threatening diseases. Pediatric oncologists are beginning to structure their practice based upon the approach to palliative care given to adults. In the first part of this report, the authors focus on technical care: comfort control and symptoms. The second part is devoted to pain management, a major aspect of pediatric palliative care. In the third part, psychosocial issues are developed, taking into account the point of view of children, siblings, parents and staff.

Adolescent↗