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Biomedical subjects

C Laurent

Publications and source records attributed to C Laurent.

At least 91 records · Page 5Linked to original sources

Linkage disequilibrium on the COMT gene in French schizophrenics and controls.

Catechol-O-methyltransferase (COMT) catalyzes the degradation of catecholamines and could therefore play a role in the etiology of schizophrenia. Moreover, microdeletions including the COMT locus have been found in schizophrenics presenting typical features of the velo-cardio-facial syndrome. In the present work, five single-strand conformation polymorphisms were detected in exons of the COMT gene. The linkage disequilibria between the polymorphisms were estimated, and the genotypic frequencies were calculated on a sample of 126 to 137 schizophrenics and 136 to 140 controls, depending on the marker. Patients and controls were matched for ethnicity and geographical origin. A trend toward association was found between schizophrenia and (i) genotype 11 of the Pml I polymorphism (p = 0.034; OR = 1.82); (ii) haplotype 1-2 for the Pml I and Bcl I polymorphisms (p = 0.022; OR = 1.75). The Pml I polymorphism is in complete linkage disequilibrium with the common Met-->Val(158) substitution, which affects the activity of the enzyme. This finding suggests a possible minor effect of COMT in a multifactorial threshold model of vulnerability to schizophrenia.

3' Untranslated Regions↗

Word priming without awareness: A new approach to circumvent explicit memory contamination.

A major methodological limitation arising in the experimental study of implicit memory is that tasks that are characterized as implicit memory tests can be seriously contaminated by the use of covert explicit memory strategies. Given the evidence indicating that brief presentation of words (below the awareness threshold of subjects) can produce semantic priming, we wondered whether rapid visual presentation of primed words might provide an avenue to produce word priming without explicit memory contamination. Normal subjects were tested for word priming on a speeded category membership decision task. Explicit or implicit encoding procedures were used in four different experiments. Results demonstrated that brief presentation of words can indeed offer a means of producing word priming in absence of explicit recognition or recall of the primed words presented during the study phase. They also showed that such priming is equivalent in degree to the priming measured when using either a conventional implicit memory design or an explicit encoding procedure prior to the study of the primes.

Adolescent↗

Intersphincteric resection with excision of internal anal sphincter for conservative treatment of very low rectal cancer.

PURPOSE: Standard surgical treatment for low rectal cancer situated below 5 cm from the anal verge or at less than 1 cm from the anal ring is abdominoperineal resection. This is because of the necessity both to achieve a sufficient distal margin and to preserve the whole of the anal sphincter. The aim of this study was to evaluate morbidity, oncologic, and functional results of intersphincteric resection with excision of the internal anal sphincter and low coloanal anastomosis for carcinomas of the anorectal junction. METHODS: From January 1990 to December 1996, 16 patients were studied prospectively. All patients had an infiltrating adenocarcinoma (5 T2 and 11 T3), located between 2.5 and 4.5 (mean, 3.6) cm from the anal verge. Rectal resection with a minimum distal margin of 2 (mean, 2.4) cm was performed in all cases; six patients underwent partial resection of the internal sphincter, and ten patients had a subtotal resection. A colonic J-pouch was associated with coloanal anastomoses in eight cases. Twelve patients had preoperative radiotherapy, 3 with concomitant chemotherapy; 5 patients had postoperative chemotherapy. RESULTS: There was no postoperative mortality. Morbidity occurred in four patients, of whom two underwent permanent colostomy after pelvic hemorrhage or anovaginal fistula. After a median follow-up of 44 (range, 11-92) months, no local recurrence was observed, and two patients died of distal metastases. The five-year actuarial survival rate was 75 percent. Continence was normal in one-half of patients and was altered in the other patients who suffered from occasional minor leaks. The median resting pressure was lower after subtotal than after partial resection of the internal sphincter (40 vs. 70 cm H2O; P = 0.02), but functional results were similar in the two groups. CONCLUSION: These preliminary results suggest that intersphincteric resection can be an alternative to abdominoperineal resection for selected rectal tumors situated at the anorectal junction, without compromising chance of cure. Functional results and continence were not altered by subtotal resection of the internal anal sphincter.

Adenocarcinoma↗

Detection of minimal residual disease in B chronic lymphocytic leukemia (CLL).

UNLABELLED: In the absence of specific chromosomal translocations the best method for detecting minimal residual disease (MRD) in B cell malignancies is based on the uniqueness of immunoglobulin (Ig) genes rearrangement. We here report a very sensitive method for assessing MRD in complete hematological remission (CHR) chronic lymphocytic leukemia (CLL) patients as defined by the international workshop on CLL (IWCLL). PATIENTS: Twelve CLL patients in CHR and complete phenotypic remission (CPR) were included in the study. Eight of them received Fludarabine (FDR), one was treated by Chop regimen, and the remaining 3 were rescued by polychemotherapy followed by autologous bone marrow transplantation (ABMT). METHODS: DNA extracted from peripheral blood lymphocytes (PBL) of each patient was amplified with VH family specific and framework 3 primers in 5' and a consensus JH primer in 3', before treatment and sequentially after the CPR completion. When no clonal rearrangement could be detected by this assay, the CDR3 sequence specific probe of the clone was used as the 3' primer, associated to the VH family specific primer in 5'. PCR products were analyzed by classical procedures in agarose and/or acrylamide gels. RESULTS: Mixtures of leukemic cells and normal PBL showed detection of a single leukemic cell among more than 10(5) normal cells. Four out of the 12 patients achieved molecular remission (MR) when employing CDR3 amplification. All 3 autografted patients were in MR, whereas only one out of the 9 patients treated by chemotherapy alone achieved MR. When using a clone specific probe, a clonal signal was observed in all cases but one (ABMT). Results presented here confirm that MR may be achieved in a few cases of B-CLL. Further studies are needed to determine the exact relationship between MRD and clinical outcome.

Aged↗

Cross-linked hyaluronan (Hylan B gel): a new injectable remedy for treatment of vocal fold insufficiency--an animal study.

After injection of hylan B gel (Hylaform), the vocal folds of rabbits were studied by light microscopy at various time-points up to 12 months. Hylan B gel is a viscoelastic cross-linked and insoluble hyaluronan derivative which behaves as a soft gel. It is non-immunogenic, non-toxic and non-inflammatory and has already been used in plastic surgery for intradermal implantations. Macroscopic examination of the injected vocal folds revealed a bulging in six of the animals, but on microscopical examination the hylan B gel was encountered in all of them. Already after 1 month, and increasingly so up to 12 months, there was an ingrowth of new connective tissue, with collagen, fibroblasts and hyaluronan within the gel. No inflammatory reaction or any sign of a foreign body reaction was observed throughout the study. Hylaform may well become useful as an injection material for augmentation of vocal folds in the treatment of vocal fold insufficiency.

Animals↗

Inter-laboratory comparison of cytogenetic endpoints for the biomonitoring of radiological workers.

PURPOSE: The evaluation of different cytogenetic endpoints of radiation damage for the biomonitoring of contract workers temporarily employed at nuclear power plants. MATERIALS AND METHODS: Blood samples from six donors were irradiated in vitro with doses ranging from 0.1 to 2Gy 60Co gamma-rays. Compared were a conventional analysis for dicentrics, the conventional micronucleus (MN) assay, the centromere micronucleus assay using p82H and an alphaAllCen pancentromeric probe, and tricolour FISH with chromosome 2, 4 and 8 DNA probes for the scoring of translocations. RESULTS: Agreement in the number of MN between Giemsa-and propidium iodine fluorescence-stained preparations was obtained. The control samples showed higher centromere positivity for the MN after FISH with the p82H probe compared with the alphaAllCen probe. The MN results with both probes showed a slight but systematic increase in the number of centromere-positive MN with dose, indicating that radiation, although principally clastogenic, also has aneuploidogenic properties. The values of the genomic translocation frequency (FG) derived from the observed translocation frequencies were systematically higher than the dicentric yields. Comparing the sensitivity of the different methods with restriction of the scoring time to 1 day for biomonitoring purposes, the centromere micronucleus assay had the lowest dose detection limit (0.1 to 0.2 Gy). CONCLUSION: This study shows that at present only the centromere micronucleus assay can combine high sensitivity with a reasonable scoring time for the biomonitoring of relatively large populations.

Adult↗

Human CD34(+) thymocyte maturation: pre-T and NK cell differentiation on neonatal thymic stromal cell culture.

The development of a simple assay for studying human T and NK lymphopoiesis from CD34 progenitors is of great interest. T and NK cells arise from a common CD34(+) immature precursor. While T cell maturation is dependent on interactions and cytokines provided by thymic stromal cells. NK maturation does not require the thymic microenvironment and primarily takes place extrathymically. In addition to models using a mouse thymic microenvironment, in vitro assays based on coculture on human fetal thymic stroma have been described. As an alternative source of fetal thymic tissue we studied the capacity of neonatal thymic epithelial cell enriched stroma to support T and NK cell differentiation. While in the fetal-based assays on NK cells were observed under the conditions used for T cell differentiation, neonatal stroma can generate CD3/TcR+ as well as CD56(+)3(-)8(+)NKR-P1(+)NK cells from both CD34(+)1(-) and CD34(+)1(+) thymocyte precursors. However, following acquisition of CD3/TcR, T-lineage cells disappeared from the culture after 2-3 weeks as a consequence of the outgrowth of the NK cells. These CD56(+)3(-) NK cells appeared to be functionally immature as they required incubation with IL2 or IL15 to lyse K562 target cells. Our data offer a simple and reliable assay for studying the reconstitution potential of T and NK cell progenitors on a monolayer of thymic epithelial cells.

Animals↗

No association between dopamine D1, D2, and D3 receptor genes and manic-depressive illness.

BACKGROUND: The dopaminergic receptor genes are candidate genes for manic-depressive illness (MDI). To test this putative involvement we used a case-control study on samples from the native population of the northwest part of France. METHODS: Fifty patients for D1 and D2, 61 patients for D3, and 86-223 controls were tested. RESULTS: No significant association was found between allelic frequencies or genotype counts and MDI, even when the data were pooled with those from published studies. CONCLUSIONS: Single mutations of either of the studied receptor genes are not major determinants of MDI.

Adult↗

Anticipation in schizophrenia: no evidence of expanded CAG/CTG repeat sequences in French families and sporadic cases.

A decrease in age of onset of schizophrenia through consecutive family generations (anticipation) has been found in several studies. Anticipation is known to result from expansion of CAG repeats in genes that determine several neurodegenerative disorders. In a previous study we analysed 26 unilineal two-generation French pedigrees and found clinical evidence of anticipation. A 10-year mean reduction in age of onset of schizophrenia was found in the second generation compared with the parental generation. The repeat expansion detection method was used to screen for CAG expansion in 21 of the 26 families with evidence of anticipation for the disease and in 59 sporadic schizophrenics and 59 controls. Comparison of the frequency distributions of CAG/CTG repeat size observed in schizophrenics and controls showed no significant difference, even when we considered familial (P = 0.23) and sporadic (P = 0.25) affected individuals separately. These results do not support the association between long CAG repeats and schizophrenia. However, the possibility that expansions with fewer than 40 repeats are involved in schizophrenia cannot be excluded.

Adult↗

CAG repeat sequences in bipolar affective disorder: no evidence for association in a French population.

Anticipation has been described in bipolar affective disorder (BPAD). However, there are conflicting results from association studies screening for a link between BPAD and CAG/CTG repeat expansions, the molecular basis of anticipation in several hereditary neurodegenerative disorders. Here, the repeat expansion detection (RED) method was used to screen for CAG repeat expansion in 119 French BPAD patients. Western blotting was also used to search for polyglutamine stretches, encoded by CAG expansion, among proteins, extracted from lymphoblastoid cell lines, from six selected familial cases. Maximum CAG/CTG repeat length did not differ significantly (P = 0.38) between the 119 BPAD patients and the 88 controls included in the study. Several categories of subgroups were used, none of which showed significant association with a long repeat. Nor was a specific protein with an unusually long polyglutamine stretch (lower detection limit, approximately 33 polyglutamines) detected in cell lysates from the familial cases studied. In conclusion, an association between a long CAG/CTG repeat and BPAD in the French population sample studied was not found. Nonetheless, a short repeat (<40 repeats) might still be implicated, and this possibility warrants further study.

Adult↗

[Acupuncture worth trying in severe tinnitus].

The article consists in a report of a study of 22 patients with disabling tinnitus, performed to elucidate the effects of a 3-month course of acupuncture (15 treatments) on the severity of tinnitus and on quality of life (QOL), as compared with those of individualised physiotherapy. The study was designed as a prospective, randomised, cross-over study with a follow-up period of one year after the final treatment. Treatment effects were evaluated in terms of the patients' VAS (visual analogue scale) ratings and answers to questionnaires, including the NHP (Nottingham Health Profile), regarding the impact of tinnitus on different aspects of QOL. Baseline NHP scores showed tinnitus patients to manifest pronounced depressive characteristics. Acupuncture was found to yield immediate relief, both in terms of loudness and disturbance of the tinnitus, and significant improvement in QOL (NHP) for three months after the conclusion of treatment. Although many patients in the subgroup with concurrent muscle tension reported beneficial effects of individualised physiotherapy, such treatment yielded no significant reduction of tinnitus loudness or disturbance due to tinnitus, and no improvement in NHP scores. In both treatment groups, however, both annoyance due to tinnitus and QOL scores had returned to pretreatment levels at one-year follow-up. Thus, the results suggest tinnitus patients to manifest depressive characteristics, and that acupuncture may yield temporary improvement in terms of tinnitus relief and QOL.

Acupuncture Therapy↗

European Multicentre Association Study of Schizophrenia: a study of the DRD2 Ser311Cys and DRD3 Ser9Gly polymorphisms.

As part of the European Multicentre Association Study of Schizophrenia (EMASS), we studied polymorphisms in the dopamine DRD2 and DRD3 receptor genes. The EMASS collaboration was established to create a large, statistically powerful sample of schizophrenic patients and controls from different European centres. Previous studies have suggested associations between schizophrenia and the Ser311Cys polymorphism in exon 7 of the dopamine DRD2 receptor gene [Arinami et al., (1994): Lancet 343:703-704] and a polymorphism Ser9gly in exon 1 of the dopamine DRD3 receptor gene [Crocq et al. (1992): J Med Genet 29:858-860]. We tested for these associations in samples of 373 and 413, and 311 and 306 patients and controls, respectively. We found no evidence for allelic association between schizophrenia and the Cys311 variant of the DRD2 receptor gene and no homozygotes for this variant were observed by any group. However, an excess of homozygotes for both alleles of the DRD3 polymorphism was observed in schizophrenic patients (chi2 = 8.54, P = 0.003, odds ratio = 1.64, 95% CI = 1.18-2.29). We also observed a significant excess of the 1-1 (Ser9Ser) genotype (chi2 = 8.13, P = 0.004, odds ratio = 1.7, 95% CI = 1.18-2.4). No evidence of heterogeneity between samples was detected and there was no evidence of an allelic association. These findings suggest that the rare Cys311 variant in exon 7 of the DRD2 receptor gene does not play a role in the pathogenesis of schizophrenia in European populations. Currently, our results do support the previous findings of an association between increased homozygosity of the Ser/Gly variant of the Dopamine D3 receptor gene and schizophrenia.

Alleles↗

Complement activation in sudden deafness.

OBJECTIVE: To test whether complement activation is associated with sudden deafness. DESIGN: Plasma samples obtained from patients in the acute phase of sudden deafness were analyzed for complement activation measured by C3bc levels and terminal complement complex. Comparisons were made with plasma samples from healthy controls. PATIENTS: Twenty-five adult patients with unilateral sudden deafness. The criteria for inclusion were symptoms of hearing loss for not longer than 14 days and a hearing loss of 35 dB or more measured at entry. RESULTS: Levels of C3bc were higher in patients compared with controls (P<.001). There were no differences in the formation of terminal complement complex in patients and controls. CONCLUSIONS: The elevated levels of C3bc in patients with sudden deafness indicate an activation of the first part of the complement cascade and therefore suspected inflammatory causes. Measurements of C3bc levels might identify patients with sudden deafness who would benefit from treatment with anti-inflammatory drugs.

Adult↗

[Functional results of the laparoscopic treatment of gastroesophageal reflux (followup greater than 2 years)].

STUDY AIM: The of this study was to evaluate functional results in 70 patients operated on for gastroesophageal reflux disease with a follow-up > 2 years, by means of a questionnaire sent to them. PATIENTS AND METHODS: Functional results were evaluated in the 60 patients who answered the questionnaire. The fundoplication (Nissen = 27, Nissen-Rosseti = 21, Toupet (n = 12) was laparoscopically performed with a mean follow-up of 3.4 years (range: 2-6.6 years). A circular wrap (either Nissen or Nissen-Rossetti) had been systematically performed except in patients who had an esophageal motility disorder, who had a partial wrap according to Toupet. RESULTS: Three patients experienced recurrent symptoms of reflux (failure rate: 5%). Thirteen patients had mild dysphagia, requiring modification of the oral intake in two cases. No patient required dilatation. Fifty patients complained of postoperative side effects: flatulence (n = 40), meteorism (n = 24), abdominal pain (n = 16), diarrhea (n = 12), impossibility either to vomit (n = 16) or to belch (n = 20). Ten patients were symptom free and had neither symptoms of reflux nor side effects. Despite undesirable side effects, 46 patients (78%) were very satisfied with the operation, six (10%) were satisfied and five (8%) were disappointed. CONCLUSION: Recurrent symptoms of reflux were rarely observed (5%) but postoperative side effects were frequent (67%). Side effects when present provide less discomfort than reflux itself. Patients must be aware of it prior to surgery. These results should be confirmed by further assessments.

Abdominal Pain↗

Second-generation three-dimensional reconstruction for rotational three-dimensional angiography.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the feasibility and accuracy of three-dimensional (3D) reconstruction techniques for digital subtraction angiography (DSA) in planning and evaluation of minimally invasive image-controlled therapy. MATERIALS AND METHODS: Using a standard, commercially available system, the authors acquired DSA images and corrected them for inherent distortions. They designed and implemented parallel and multiresolution versions of cone-beam reconstruction techniques to reconstruct high-resolution targeted volumes in a short period of time. Testing was performed on anatomically correct, calibrated in vitro models of a cerebral aneurysm. These models were used with a pulsatile circulation circuit to allow for blood flow simulation during DSA, computed tomographic (CT) angiography, and magnetic resonance (MR) angiography image acquisitions. RESULTS: The multiresolution DSA-based reconstruction protocol and its implementation allowed the authors to achieve reconstruction times and levels of accuracy for the volume measurement of the aneurysmal cavities that were considered compatible with actual clinical practice. Comparison with data obtained from other imaging modalities shows that, besides vascular tree depiction, the DSA-based true 3D technique provides volume estimates at least as good as those obtained from CT and MR angiography. CONCLUSION: The authors demonstrated the feasibility and potential of true 3D reconstruction for angiographic imaging with DSA. On the basis of the model testing, this work addresses both the timing and quantification required to support minimally invasive image-controlled therapy.

Algorithms↗

A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia.

We performed a meta-analysis of over 30 case-control studies of association between schizophrenia and a bi-allelic, Bali polymorphism in exon 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07-1.35) in the combined sample of 5351 individuals. No significant heterogeneity was detected between samples and the effects did not appear to be the product of publishing bias. In addition we undertook an independent, family-based association study of this polymorphism in 57 parent/proband trios, taken from unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR) = 2.7, 95% CI = 1.35-5.86). Although no significant allelic association was observed, a significant association was detected with the 1-1 genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when the results of the family-based association study were included in the meta-analysis, the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI = 1.09-1.38). The results of the meta-analysis and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the Bali polymorphism of the D3 receptor gene, or between a locus in linkage disequilibrium with it.

Alleles↗

Risk factors for anastomotic leakage after resection of rectal cancer.

BACKGROUND: The most important surgical complication following rectal resection with anastomosis is symptomatic anastomotic leakage, which is associated with a 6-22 per cent mortality rate. The aim of this retrospective study was to evaluate the risk factors for clinical anastomotic leakage after anterior resection for cancer of the rectum. METHODS: From 1980 to 1995, 272 consecutive anterior resections for rectal cancer were performed by the same surgical team; 131 anastomoses were situated 5 cm or less from the anal verge. The associations between clinical anastomotic leakage and 19 patient-, tumour-, surgical-, and treatment-related variables were studied by univariate and multivariate analysis. RESULTS: The rate of clinical anastomotic leakage was 12 per cent (32 of 272). Multivariate analysis of the overall population showed that only male sex and level of anastomosis were independent factors for development of anastomotic leakage. The risk of leakage was 6.5 times higher for anastomoses situated less than 5 cm from the anal verge than for those situated above 5 cm; it was 2.7 times higher for men than for women. In a second analysis of low anastomoses (5 cm or less from the anal verge; n = 131), obesity was statistically associated with leakage. CONCLUSION: A protective stoma is suitable after sphincter-saving resection for rectal cancer for anastomoses situated at or less than 5 cm from the anal verge, particularly for men and obese patients.

Adult↗

Dextranomeres in hyaluronan (DiHA): a promising substance in treating vocal cord insufficiency.

The morphology of the rabbit vocal cord was studied after injecting a mixture of dextranomere microspheres in sodium hyaluronan solution (DiHA), two substances that are nonimmunogenic and biocompatible. DiHA is already in clinical use as a space filler in pediatric urology (Deflux R). Specimens from injected vocal cords were investigated by light microscopy at different time intervals up to 6 months after injection. On macroscopic examination a bulge was seen in the injected vocal cord, and on microscopic examination new fibrous connective tissue developed. Throughout the study a weak inflammatory reaction was observed, but no foreign body reaction. Hyaluronan disappeared from the injected site within 1 week, but the dextranomeres remained and were recovered intact up to 6 months after injection. The dextranomeres recruited fibroblasts that generated new collagen, resulting in endogenous soft tissue augmentation. It is conceivable that DiHA may become a useful injection material for treatment of vocal cord insufficiency.

Animals↗