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Biomedical subjects

A Laurent

Publications and source records attributed to A Laurent.

At least 37 records · Page 2Linked to original sources
PubMed2000

Executive/attentional performance and measures of schizotypy in patients with schizophrenia and in their nonpsychotic first-degree relatives.

Previous studies of executive/attentional functions have found impairments in nonpsychotic first-degree relatives of patients with schizophrenia. The aims of this study were: (1) to replicate these findings by three laboratory measures of attention/information processing - a continuous performance test (DS-CPT), a forced-choice span of apprehension task (SPAN), and a digit symbol substitution test (DSST), and by a series of neuropsychological tests sensitive to prefrontal cortical damage - Trail Making A and B, verbal fluency (VFT), Stroop Color and Word Test (Stroop), and Wisconsin Card Sorting Test (WCST); (2) to investigate whether such executive/attentional deficits are associated with schizotypal traits assessed using the social anhedonia, physical anhedonia, perceptual aberration and magical ideation scales (Chapman, L.J., Chapman, J.P., Raulin, M.L. 1976. Scales for physical and social anhedonia. J. Abnorm. Psychol. 85, 374-382; Chapman, L.J., Chapman, J.P., Raulin, M.L., 1978. Body-image aberration in schizophrenia. J. Abnorm. Psychol. 87, 399-407; Eckblad, M., Chapman, L.J., 1983. Magical ideation as an indicator of schizotypy. J. Consult. Clin. Psychol. 51, 215-225). In both patient and relative groups, performance was significantly poorer on the DSST, VFT and Trail B, and the reaction time on the SPAN was significantly longer. These neuropsychological impairments were present as much in siblings as in parents of schizophrenic patients; age did not appear to cancel differences between the relative and control groups. In the relative group, the four scores of schizotypy were at an intermediate level between those of patient and control groups, and the social anhedonia and perceptual aberration scores tended to be significantly different between the relative and the control groups. Only two significant correlations were found between the neuropsychological performance and the measures of schizotypy.

Adolescent↗
PubMed2000

Metabolism of 4-hydroxynonenal, a cytotoxic product of lipid peroxidation, in rat precision-cut liver slices.

4-Hydroxy-2-nonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert several biological and cytotoxic effects. The in vitro metabolism of [4-(3)H]-HNE by rat precision-cut liver slices was investigated. Liver slices rapidly metabolize HNE - about 85% of 0.1 microM [4-(3)H]-HNE was degraded within 5 min of incubation. The main metabolites of HNE identified were 4-hydroxynonenoic acid (HNA), glutathione-HNE-conjugate (HNE-GSH), glutathione-1,4-dihydroxynonene-conjugate (DHN-GSH) and cysteine-HNE-conjugate (HNE-CYS). Whereas glutathione conjugation demonstrated saturation kinetics (K(m)=412.2+/-152.7 microM and V(max)=12.3+/-2.5 nmol h(-1) per milligram protein), HNA formation was linear up to 500 microM HNE in liver slices. In contrast to previous reports, no trace of the corresponding alcohol of the HNE, 1,4-dihydroxynon-2-ene was detected in the present study. Furthermore, the beta-oxidation of HNA including the formation of tritiated water was demonstrated. The identification of 4-hydroxy-9-carboxy-2-nonenoic acid and 4,9-dihydroxynonanoic acid demonstrated that omega-oxidation significantly contributes to the biotransformation of HNE in liver slices.

Aldehydes↗
PubMed2000

Alteration of event related potentials in siblings discordant for schizophrenia.

This study was aimed at confirming that auditory event related potential (ERP) abnormalities are indicators of vulnerability to schizophrenia. Auditory ERP performances were assessed at Fz, Cz, and Pz, with an oddball paradigm, in 21 clinically stable patients with schizophrenia, 21 of their healthy biological full siblings and 21 control subjects. The evoked response did not differ between the three groups on N200 waves. Compared to controls, patients with schizophrenia exhibited reduced amplitudes of N100 and P300, and prolonged latency of P300, while their siblings showed prolonged latency of P200 and P300. Among the patients with schizophrenia, ERP abnormalities did not correlate with age, clinical state, duration of illness or antipsychotic treatments. Although other conditions also accounted for alterations of the same type, ERP abnormalities may represent a neurobiological marker of the genetic vulnerability to schizophrenia, independent of phenotypic expression.

Adult↗
PubMed2000

Isolation from rat urine and human liver microsomes and identification by electrospray and nanospray tandem mass spectrometry of new malagashanine metabolites.

Malagashanine has been isolated from indigenous madagascan Strychnos myrtoides alkaloids used traditionally to treat malaria. This alkaloid was found to enhance the action of chloroquine against chloroquine-resistant strains of Plasmodium falciparum when combined with classical antimalarial drugs (chloroquine, quinine). The present study was carried out in order to investigate by electrospray mass and tandem mass spectrometry and NMR spectroscopy the structure of two new metabolites isolated from rat urine and human liver microsomes. We were able to demonstrate the presence of two new metabolites of malagashanine corresponding to a malagashanine N-demethylated metabolite and to the oxidation of malagashanine in the alpha-position of the N-methyl group to produce a carbinolamine function. The latter metabolite may be subject to ring and open-chain tautomerism effects and dimeric species were detected in the electrospray mass spectrum.

Alkaloids↗
PubMed2000

The effects of ketoconazole on ziprasidone pharmacokinetics--a placebo-controlled crossover study in healthy volunteers.

AIMS: To assess the effects of multiple oral doses of ketoconazole on the single-dose pharmacokinetics of oral ziprasidone HCl. METHODS: This was a 14-day, open-label, randomized, crossover study in 14 healthy subjects aged 18-31 years. Group 1 received oral ketoconazole 400 mg once daily for 6 days, followed by a 2 day wash-out period and 6 days of placebo administration. Group 2 received placebo followed by ketoconazole. Single oral doses of ziprasidone HCl 40 mg were administered on days 5 and 13 in both groups. Ziprasidone pharmacokinetic parameters were compared between placebo and ketoconazole administration periods. RESULTS: Co-administration of ziprasidone with ketoconazole was associated with a modest increase in ziprasidone exposure; mean ziprasidone AUC(0,infinity) increased by 33%, from 899 ng ml(-1) h with placebo to 1199 ng ml(-1) h with ketoconazole. Mean Cmax increased by 34%, from 89 ng ml(-1) to 119 ng ml(-1), respectively. The treatment effect on both of these parameters was statistically significant (P<0.02). Most adverse events were of mild intensity. There were no serious adverse events, laboratory abnormalities, abnormal ECGs, or clinically significant alterations in vital signs throughout the study. CONCLUSIONS: The concurrent administration of ketoconazole and ziprasidone led to modest, statistically significant increases in ziprasidone exposure, although the changes seen were not considered clinically relevant. This suggests that other inhibitors of CYP3A4 are unlikely to significantly affect the pharmacokinetics of ziprasidone.

Adolescent↗
PubMed2000

The effect of carbamazepine on the steady-state pharmacokinetics of ziprasidone in healthy volunteers.

AIMS: To evaluate the effect of steady-state carbamazepine administration on the steady-state pharmacokinetics of ziprasidone in healthy young adults, in an open, randomised, parallel-group study. METHODS: Twenty-five subjects were randomized to one of two treatment groups. Group 1 received 20 mg ziprasidone twice daily on days 1 and 2, and a single dose on day 3. A single 100 mg dose of carbamazepine was given once daily on days 5 and 6 and twice daily on days 7 and 8, followed by 200 mg twice daily until day 28 and on the morning only on day 29. Ziprasidone 20 mg was also administered twice daily on days 26 and 27 and in the morning only on day 28. Group 2 received the same treatment regimen with carbamazepine replaced by placebo. Pharmacokinetic data were obtained on days 3 and 28. RESULTS: Nine subjects in group 1 and 10 in group 2 completed all three treatment periods (ziprasidone, carbamazepine or placebo; and ziprasidone plus carbamazepine or placebo). Carbamazepine administration to group 1 was associated with modest reductions in ziprasidone exposure, with mean decreases in ziprasidone AUC(0,12 h) and Cmax values of 36% and 27%, respectively, on day 28 compared with day 3 (P<0.03). The mean differences between day 28 and day 3 ziprasidone AUC(0,12 h) and Cmax values were also statistically significantly greater in the carbamazepine group than in the placebo group. The mean half-life of ziprasidone decreased by 1 h from day 3 to day 28 in the subjects receiving carbamazepine, compared with virtually no change in the placebo group. All adverse events were mild or moderate in severity and there were no serious adverse events, or clinically significant changes in ECGs and vital signs throughout the study. CONCLUSIONS: Induction of CYP3A4 with carbamazepine led to a modest reduction (<36%) in steady-state exposure to ziprasidone that is believed to be clinically insignificant.

Adult↗
PubMed2000

Multicentre, randomized clinical trial of primary versus secondary sigmoid resection in generalized peritonitis complicating sigmoid diverticulitis.

BACKGROUND: The best way to manage generalized peritonitis complicating sigmoid diverticulitis is controversial. This randomized clinical trial involved a comparison of primary resection and suture, drainage with proximal colostomy followed by secondary resection. METHODS: From January 1989 to December 1996, 105 patients of mean(s.d.) age 66(14) (range 32-91) years were randomized to undergo primary or secondary resection. The main endpoint was occurrence of generalized or localized postoperative peritonitis. The Mannheim Peritonitis Index score was calculated for each patient to check for comparability of groups. RESULTS: Postoperative peritonitis occurred less often after primary than secondary resection whether considering the first procedure only (one of 55 patients versus ten of 48; P < 0.01) or all procedures (one of 55 versus 12 of 48; P < 0.001). Likewise, early reoperation was performed less often following primary resection than secondary resection (two of 55 versus nine of 48 (P < 0.02) and two versus 11 (P < 0.01)), leading to a shorter median first hospital stay for patients having primary resection (15 days) than for those undergoing secondary resection (24 days) (P < 0.05). The mortality rate did not differ significantly with regard to operative policy (primary resection 24 per cent versus secondary resection 19 per cent) or type of peritonitis (faeculent 27 per cent versus purulent 19 per cent). No patient died following a second or third procedure. CONCLUSION: Primary resection is superior to secondary resection in the treatment of generalized peritonitis complicating sigmoid diverticulitis because of significantly less postoperative peritonitis, fewer reoperations and shorter hospital stay.

Adult↗
PubMed2000

Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization.

OBJECTIVE: To assess the influence of preoperative portal vein embolization (PVE) on the long-term outcome of liver resection for colorectal metastases. SUMMARY BACKGROUND DATA: Preoperative PVE of the liver induces hypertrophy of the remnant liver and increases the safety of hepatectomy. METHODS: Thirty patients underwent preoperative PVE and 88 patients did not before resection of four or more liver segments. PVE was performed when the estimated rate of remnant functional liver parenchyma (ERRFLP) assessed by CT scan volumetry was less than 40%. RESULTS: PVE was feasible in all patients. There were no deaths. The complication rate was 3%. The post-PVE ERRFLP was significantly increased compared with the pre-PVE value. Liver resection was performed after PVE in 19 patients (63%), with surgical death and complication rates of 4% and 7% respectively. PVE increased the number of resections of more than four segments by 19% (17/88). Actuarial survival rates after hepatectomy with or without previous PVE were comparable: 81%, 67%, and 40% versus 88%, 61%, and 38% at 1, 3, and 5 years respectively. CONCLUSIONS: PVE allows more patients with previously unresectable liver tumors to benefit from resection. Long-term survival is comparable to that after resection without PVE.

Aged↗
PubMed2000

Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors.

OBJECTIVE: To assess feasibility, risks, and patient outcomes in the treatment of colorectal metastases with two-stage hepatectomy. SUMMARY BACKGROUND DATA: Some patients with multiple hepatic colorectal metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization, or combined with a locally destructive technique. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. In selected patients with irresectable multiple metastases not amenable to a single hepatectomy procedure, two-stage hepatectomy might offer a chance of long-term remission. METHODS: Of consecutive patients with conventionally irresectable colorectal metastases treated by chemotherapy, 16 of 398 (4%) became eligible for curative two-stage hepatectomy combined with chemotherapy and adjuvant nonsurgical interventions as indicated. RESULTS: Two-stage hepatectomy was feasible in 13 of 16 patients (81%). There were no surgical deaths. The postoperative death rate (2 months or less) was 0% for the first-stage procedure and 15% for the second-stage one. Postoperative complication rates were 31% and 45%, respectively, with only one complication leading to reoperation. The 3-year survival rate was 35%, with four patients (31%) disease-free at 7, 22, 36, and 54 months. Median survival was 31 months from the second hepatectomy and 44 months from the diagnosis of metastases. CONCLUSIONS: Two-stage hepatectomy combined with chemotherapy may allow a long-term remission in selected patients with irresectable multiple metastases and increases the proportion of patients with resectable disease.

Aged↗
PubMed2000

Effects of wheat bran and Olestra on objective measures of stool and subjective reports of GI symptoms.

OBJECTIVE: The aim of this study was to compare the effects of two nondigested, nonabsorbed dietary components on objective and subjective measures of gastrointestinal (GI) function. METHODS: A placebo-controlled parallel study compared the effects of wheat bran (20 g/day or 40 g/day in cereal), a well-known dietary fiber, with those of olestra (20 g or 40 g/day in potato chips), a nonabsorbed fat, on stool output, stool apparent viscosity (log peak force for extrusion [PF]), stool water content, and GI symptoms. Sixty subjects resided on a metabolic ward for 9 days: 3 days baseline and 6 days treatment. RESULTS: Compared with placebo, consumption of 20 g/day wheat bran for 6 days resulted in a rapid (within 38 h) increase in mean (+/-SE) stool output (placebo, 150 +/- 29 g/day; bran, 246 +/- 35 g/day, p < 0.05), a directional increase in mean stool water content (placebo, 81.2 +/- 0.8%; bran, 83.9 +/- 0.8%), stool water output (placebo, 159 +/- 54 g/day; bran, 238 +/- 30 g/day), and bowel movement frequency (BM/day) (placebo, 2.2 +/- 0.4; bran, 2.6 +/- 0.4), and no stool-softening effect (placebo log PF, 2.9 +/- 0.1 g; bran log PF, 2.9 +/- 0.1 g). Wheat bran 40 g/day results were not significantly different from wheat bran 20 g/day. Compared with placebo, consumption of olestra 20 g/day and 40 g/day for 6 days showed no significant difference in mean stool output (151 +/- 18 g/day and 204 +/- 28 g/day, respectively), mean BM frequency (1.8 +/- 0.2 BM/day and 2.1 +/- 0.3 BM/day, respectively), and stool water output (138 +/- 13 g/day and 184 +/- 31 g/day, respectively), a significant (p < 0.05) decrease in stool water content (75.5 +/- 1.7% and 72.6 +/- 2.2%, respectively), and either no effect on stool apparent viscosity (olestra 20 g/day, mean log PF, 3.0 +/- 0.1 g) or a gradual stool-softening effect beginning study day 6 (olestra 40 g/day, log PF, 2.7 +/- 0.1 g). None of the treatment groups showed a significant increase in GI symptoms compared with placebo. CONCLUSIONS: Consumption of wheat bran in excess of levels in a typical Western diet significantly increased stool output, but did not soften normal-viscosity stool nor result in an increase in common GI symptoms. The observed plateau effect for wheat bran at 40 g/day suggests a maximal mechanical stimulatory effect. Consumption of olestra in excess of usual snacking conditions did not result in a significant increase in stool output or common GI symptoms. At the highest level tested, olestra resulted in a gradual stool-softening effect after several days of consumption.

Adolescent↗
PubMed1999

Attentional deficits in patients with schizophrenia and in their non-psychotic first-degree relatives.

The aim of this study was to investigate whether non-psychotic relatives of schizophrenic probands have deficits in sustained attention as measured by the Continuous Performance Test, Identical Pairs version (CPT-IP) and whether such deficits are associated with negative schizotypal personality disorders. The study subjects were 23 schizophrenic probands, 45 of their first-degree relatives and 36 normal controls. For each subject, attention was assessed during five conditions (2 standard, 2 slow, 1 easy) of visual stimuli (numbers and shapes). Schizotypy status was determined with the physical anhedonia and social anhedonia scales of Chapman et al. (Chapman, L.J., Chapman, J.P., Raulin, M.L., 1976. Scales for physical and social anhedonia. Journal of Abnormal Psychology 42, 374-382). The CPT-IP sensitive index d' in the standard shape condition was significantly lower in schizophrenics and in their relatives than in controls. For all d' values, the percentage of impaired first-degree relatives was at an intermediate level between patients and control individuals. Furthermore, the schizophrenic probands made more random errors in the standard and in the slow number conditions than the other two groups. None of the schizotypy measures correlated with the CPT-IP deficits. These results suggest that spatial sustained attention deficit may be a vulnerability marker for schizophrenia; however, this deficit and the negative dimension of schizotypal personality disorders may be distinct traits.

Adult↗
PubMed1999

Chiral and steric effects in the efficient binding of alpha-anomeric deoxyoligonucleoside N-alkylphosphoramidates to ssDNA and RNA.

We report hybridization properties of new phosphate-modified alpha-oligonucleoside analogs with non-ionic or cationic internucleotide linkages such as methoxy-ethylphosphoramidate (PNHME), phosphoromorpholi-date (PMOR) and dimethylaminopropylphosphor-amidate (PNHDMAP). First we evaluated the chirality effect of the phosphorus atom on the affinity of alpha- or beta-dodecanucleoside phosphodiesters containing one chirally enriched N -alkylphosphoramidate linkage located in the middle of the sequence d(TCTT-AA*CCCACA). As for P-substituted beta-oligonucleo-tides, a difference in binding behavior between the two diastereoisomers (difference in Delta T (m)) exists in the hybridization properties of alpha-analogs when DNA was the target but this effect was not detrimental to duplex stability. This effect was considerably reduced when RNA was the target. Secondly we studied the effect of steric hindrance around phosphorus on the affinity of fully modified beta- and alpha-oligonucleoside N -alkylphosphoramidates for their DNA and RNA targets. This effect was very weak with alpha-analogs whereas it was more pronounced with beta-oligos. PNHME-modified alpha-oligonucleosides formed more stable duplexes with DNA (Delta T (m)+9.6 degrees C) and RNA (Delta T (m)+1.4 degrees C) targets than the 'parent' phosphodiester. Finally, base pairing specificity of these alpha-oligonucleo-side N -alkylphosphoramidates for their targets was found to be as high as for natural oligonucleoside phosphodiesters.

Alkylation↗
PubMed1999

Neuropsychological functioning among non-psychotic siblings and parents of schizophrenic patients

Several studies have shown subtle neuropsychological deficits in healthy relatives of schizophrenic patients. However, older relatives and parents have been less frequently assessed than younger adult relatives and siblings. Furthermore, some areas of neuropsychological functioning such as memory and learning have been little studied. Thirty-seven 22-70-year-old non-psychotic parents and siblings of schizophrenic patients were compared to 37 healthy control subjects on a battery of neuropsychological tests (Trail Making, parts A and B, verbal fluency, Wisconsin Card Sorting Test, and four subtests of the Wechsler Memory Scale-Revised: logical memory, design reproduction, verbal paired associates and digit span). Relatives did not differ from control subjects on Wisconsin Card Sorting Test performance and on visual memory, but were significantly impaired on verbal fluency; more subtle deficits were found on Trail Making, part B, digit span and paired associates. A higher proportion of relatives than control subjects showed impairment on verbal fluency and verbal memory. These neuropsychological weaknesseswere present as much in siblings as in parents of schizophrenic patients, and age did not cancel differences between relatives and control subjects. Thus, these subtle deficits seem to be potential phenotypic markers of schizophrenia.

Journal Article↗
PubMed1999

Auditory event-related potentials and clinical scores in unmedicated schizophrenic patients.

Event-related potentials (ERPs) have been widely examined in schizophrenic patients. However, although neuroleptic medication could be a potentially confounding variable, studies with unmedicated patients are relatively scarce. The present work was undertaken to determine whether ERP abnormalities persist in stabilized schizophrenic patients after drug withdrawal. In addition, ERP amplitudes and latencies were compared with clinical ratings (the Positive and Negative Syndrome Scale, PANSS) by means of Spearman rank order correlation coefficients. The P300 and N200 responses to rare tones and the P200 and N100 responses to frequent tones were recorded in 20 clinically stabilized drug-free schizophrenic patients and 19 age-matched control subjects during a two-tone discrimination task. Major findings were that the schizophrenic patients had reduced P300, N200 and N100 amplitudes and an increased P300 latency. The P300 amplitude was negatively correlated with age in patients. The P200 latency was negatively correlated with the PANSS positive syndrome score. The ERP abnormalities shown in this study appear to be enduring traits of the disorder as they persist in stabilized patients even after drug withdrawal.

Adult↗
PubMed1999

Effects of contrast media on blood rheology: comparison in humans, pigs, and sheep.

PURPOSE: To compare whole blood viscosity and erythrocyte aggregation in humans, pigs, and sheep, before and after adding water-soluble iodinated contrast medium (CM). METHODS: Two CMs were studied: iopromide (nonionic) and ioxaglate (ionic). The blood-CM viscosity was measured with a Couette viscometer. Erythrocyte aggregation was measured with an erythroaggregometer. RESULTS: The blood-CM viscosity was increased up to +20% (relative to pure blood) with a CM concentration of 0%-10%. At CM concentrations from 10% to 50%, the viscosity decreased. The disaggregation shear stress was increased (relative to pure blood) at low CM concentration (0%-10%). When the CM concentration increased from 10% to 20%, the disaggregation shear stress was decreased, except with the pig blood-ioxaglate mixture. CONCLUSION: At low CM concentration the blood viscosity was increased in pig, sheep, and humans and the disaggregation shear stress was increased in pig and humans. The aggregation of sheep blood was too low to be detected by the erythroaggregometer. This rise can be explained by the formation of poorly deformable echinocytes. At higher CM concentration, the viscosity and the disaggregation shear stress decreased in relation to the blood dilution. We conclude that pig blood and sheep blood can both be used to study the effect of CM injection on blood viscosity. Nevertheless, the rheologic behavior of pig blood in terms of erythrocyte aggregation is closer to that of human blood than is sheep blood when mixed with CM. Pigs could thus be more suitable than sheep for in vivo studies of CM miscibility with blood during selective cannulation procedures.

Animals↗
PubMed1999

A model for evaluating injectable bone replacements in the vertebrae of sheep: radiological and histological study.

We developed a bone-defect model in the vertebrae of sheep. Forty four cavities were prepared in the upper lumbar vertebrae of 11 sheep using a biopsy trocar via a posterior-lateral extracanal percutaneous route and the location was monitored by radiology with a brilliance amplifier. The cavities were 3 mm in diameter. The histological study was performed on 15 cavities which were left empty to give reference data for the model. Histological and histomorphometry results showed that 67% of the surface area of the empty cavities was still empty 3 months after their preparation. Thus, the natural regenerative capacity of vertebral trabecular bone is limited. We performed preliminary percutaneous injections of polymethylmethacrylate (PMMA) and nacre powder to assess whether this bone-defect model would be suitable for further studies on bone repair. Cavities were successfully filled with nacre powder (21 cavities) or PMMA (8 cavities) while monitoring the process by interventional radiology. The experimental sheep vertebrae defect system is reproducible and appears to be a suitable model for testing injectable biomaterials for treating bone loss.

Animals↗
PubMed1999

Violence of French adolescents toward their parents: characteristics and contexts.

PURPOSE: To determine the social, familial, and psychiatric characteristics of children who batter their parent(s); and to report clinical vignettes of this phenomenon and contexts which precipitate such violence. METHODS: In this retrospective study, we analyzed the medical records of the 645 children hospitalized in a child and adolescent psychiatry department between 1987 and 1996. RESULTS: The principle findings were that: (a) 3.4% of the patients demonstrate parent battering; (b) the average age of parent batterers is 14 years old, and they are predominately male; and (c) their mothers are more often the victims than their fathers, and there is a high frequency of psychiatric disorders among parents. Seven clinical vignettes have been presented to represent different family contexts of the 22 cases of domestic violence in this study. CONCLUSIONS: Further studies are needed to deepen our knowledge of violence perpetrated by adolescents toward their parents. A better knowledge of etiological mechanisms involved would permit more preventative action for families at risk.

Adolescent↗