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Biomedical subjects

M Dreyfus

Publications and source records attributed to M Dreyfus.

At least 91 records · Page 5Linked to original sources
PubMed1997

Clinical features in 36 patients homozygous for the ARG 506-->GLN factor V mutation.

We analyzed the clinical features of 36 patients homozygous for the Arg 506 to Gln factor V mutation and found a circumstantial event at risk for thrombosis in 29 of the 31 patients with thrombosis. The most frequent predisposing factors were the post-partum period and the use of oral contraceptives in women, and surgery in both sexes. Venous thrombosis recurred in 48% of the patients. One patient had a myocardial infarction at age 33 years, and also had an antiphospholipid syndrome. Homozygous Gln 506 mutation leads to far less severe thrombotic complications than homozygous protein C and protein S deficiencies and does not seem to predispose patients to arterial thrombosis.

Adult↗
PubMed1996

The lacZ mRNA can be stabilised by the T7 late mRNA leader in E coli.

Previous work from this laboratory has shown that T7 RNA polymerase outpaces ribosomes in vivo, generating naked mRNA stretches which may be nuclease-sensitive. In particular, lacZ transcripts synthesised this way are highly unstable and yield little beta-galactosidase. We have argued that most of these transcripts are prematurely inactivated via an RNase E cleavage that occurs ahead of the leading ribosome, whereas a few escape this initial cleavage and are translated normally. Presumably, these rescued transcripts are later inactivated non-nucleolytically and subsequently scavenged by a process partially controlled by RNase E, as for the natural lacZ mRNA. In contrast, despite being synthesised by T7 RNA polymerase, T7 late transcripts are stable. The 5' regions of several of these transcripts, exemplified by the gene 10 mRNA, harbour hairpin structures which may act as barriers against RNase E action. To test whether these structures are indeed 5' stabilisers, we replaced the lacZ leader sequence by the corresponding region from T7 gene10. This replacement yielded a ca 2.9-fold increase in beta-galactosidase yield per transcript. This increase vanished in the presence of the rne-50 mutation which inactivates RNase E, and therefore it reflects a protection of the transcript against RNase E-dependent inactivation. Yet, the leader replacement did not stabilise the transcript chemically. We propose that this replacement inhibits the initial cleavage step but somehow facilitates the subsequent scavenging process.

Bacteriophage T7↗
PubMed1996

Diagnostic value of endocervical curettage during colposcopy.

A retrospective study including patients with cytology, colposcopy and endocervical curettage (ECC) was carried out to compare ECC outcomes to final diagnosis. ECC was performed in 68 cases for a discordance between cytology and colposcopy and in 85 cases because the lesion was incompletely visible. Complete concordance between ECC and final diagnosis was obtained in 123 cases. ECC overestimated diagnosis in eight cases (5 true false positives) and underestimated it in 20 cases (6 true false negatives). Among the latter, ECC failed to recognize invasion in seven cases. Sensitivity, specificity, positive and negative predictive values of ECC to diagnose high grade cervical intraepithelial neoplasia (CIN) and invasive lesions together were 84%, 97%, 95% and 90%, respectively. Outcomes to diagnose invasive lesions were 22%, 100%, 100% and 95%, respectively. ECC sensitivity to diagnose endocervical lesions is satisfactory but its sensitivity to establish the diagnosis of invasion is very low. Consequently, a conization is advisable when ECC has diagnosed an endocervical lesion, especially a high grade CIN.

Adult↗
PubMed1996

Risk of cervical stenosis after large loop excision or laser conization.

OBJECTIVE: To assess the frequency of cervical stenosis in patients treated by laser conization or the loop electrosurgical excision procedure and to determine the preoperative and therapeutic factors associated with its occurrence. METHODS: Two hundred fifty-five women treated by laser conization and 277 treated by loop electrosurgical excision procedure were followed regularly by postoperative colposcopy for mean periods of 38 and 16 months, respectively. Stenosis was defined as cervical narrowing that prevented insertion of a 2.5-mm Hegar dilator. RESULTS: Thirty-eight cases of cervical stenosis, of which seven were complete, were diagnosed up to 28 months after treatment. The risk of postoperative cervical stenosis was higher for patients over 50 years of age (relative risk [RR] 3.07, 95% confidence interval [95% CI] 1.30, 7.26; P = .031), for those with a totally endocervical lesion (RR 3.79, 95% CI 1.88, 7.62; P = .001), for those with an excision 20 mm high or greater (RR 2.96, 95% CI 1.63, 5.38; P = .005), and for those with laser conization (RR 2.35, 95% CI 1.24, 4.46; P = .009). Parity, menopause, previous treatment for cervical intraepithelial neoplasia, satisfactory colposcopy, size of the lesion, its histologic diagnosis, and the extent of excision did not increase the risk for cervical stenosis. Excision was not as high with loop electrosurgical excision as with laser conization (14.3 +/- 5.0 mm versus 20.2 +/- 6.0 mm). The height of excision (RR 1.95, 95% CI 1.02, 3.76; P = .04) and a totally endocervical lesion (RR 5.07, 95% CI 1.96, 14.44; P = .001) were the only independent factors associated with postoperative stenosis identified by a multivariate analysis using logistic regression. CONCLUSION: The height of excision and a totally endocervical lesion were the main factors associated with cervical stenosis. The decreased risk associated with the loop electrosurgical excision procedure seems to be due to a shorter endocervical excision.

Adolescent↗
PubMed1996

Prenatal diagnosis of unilateral tibial hemimelia.

We describe a case of unilateral tibial agenesis which was initially observed at 21 weeks' gestation. Unlike bilateral tibial hemimelia syndrome, a rare autosomal dominant condition, unilateral tibial agenesis, which accounts for about three-quarters of all newborns with this condition, has not previously been described. This case could have been a sporadic abnormality but, in view of the association with other observations (distal bifurcation of the femur, club foot), could be considered as an autosomal recessive inherited condition with variable penetrance. Ultrasonographic features and the genetic prognosis are discussed.

Adult↗
PubMed1996

Screening primiparous women and newborns for fetal/neonatal alloimmune thrombocytopenia: a prospective comparison of effectiveness and costs. Immune Thrombocytopenia Working Group.

A prospective study was conducted in three maternity wards to compare the medical outcomes and the costs of two screening strategies for the detection of fetal/neonatal alloimmune thrombocytopenia (FMAIT). A total of 2066 primiparas and 6081 newborns were included. Fifty-two primiparous women with HPA-1b phenotype were found, and 45 were followed during pregnancy. Four women developed antibodies, and two fetuses exhibited FMAIT; therefore, the prevalence of anti-HPA-1a was 2 per 1000, and the prevalence of FMAIT 1 per 1000. Forty-eight thrombocytopenic newborns were found out of a total of 5632 blood samples. Five were HPA-1a children whose mothers were HPA-1b. The cost-effectiveness of screening all primiparous women was $45,000 and of screening all newborns is $18,000-per anti-HPA-1a alloimmunization diagnosed. Costs per fetal death or disability averted were $500,000 for the primiparous strategy and $225,000 for the newborn strategy. In conclusion, screening newborns for neonatal alloimmune thrombocytopenia is more cost-effective than screening primiparous women.

Antigens, Human Platelet↗
PubMed1996

Plasma cyclic GMP concentrations and their relationship with changes of blood pressure levels in pre-eclampsia.

BACKGROUND: One of the possible mechanisms responsible for pre-eclampsia is a loss of efficiency of the L-arginine-nitric oxide pathway with subsequent inactivation of the guanylyl cyclases of the vascular smooth muscle cells. As a result there should be a decrease in plasma cyclic 3'-5' guanosine monophosphate (cGMP) concentrations in pre-eclampsia. We assessed the behavior of this nucleotid in the plasma of pre-eclamptic women. SUBJECTS AND METHODS: Sixteen pre-eclamptic women, 16 normotensive pregnant women matched for gestational age and six nonpregnant controls were investigated. Arterial blood pressure was recorded at inclusion time and then once-a-day until the fourth day after delivery concomitantly with the collection of blood samples for determining plasma cGMP, atrial natriuretic peptides (ANP), creatinine, uric acid and platelet counts. Also 24 h urines were simultaneously collected to calculate renal clearance of cGMP. RESULTS: Before the initiation of antihypertensive treatment, plasma cGMP levels were significantly higher (p < 0.01) in pre-eclampsia women as compared both to pregnant normotensive controls and nonpregnant women (7.02 +/- 0.9 versus 4.8 +/- 0.76 versus 1.93 +/- 0.15 pmol.ml-1, p < 0.01). Under antihypertensive treatment, cGMP levels decreased significantly (p < 0.05) to 5.48 +/- 0.9 pmol.ml-1. The increase of plasma cGMP was associated with high ANP levels; the likelihood that a renal impairment could account for an increase in plasma cGMP was ruled out because the clearance of creatinine was not impaired. Similarly the possibility of a significant linear correlation between cGMP levels and blood pressure values or biological data was excluded in these women. CONCLUSION: Plasma cGMP concentrations are increased in pre-eclampsia. They decrease to control values when blood pressure returns to normal values; they indicate enhanced guanylyl cyclase activation by ANP and additional factors, but cannot be considered as a direct index of the severity of pre-eclampsia.

Adult↗
PubMed1996

[Fetal and neonatal immune thrombocytopenias].

Fetal and neonatal immune thrombocytopenias with platelet count less than 150.10(9)/l, result from transplacental passage of maternal platelet-specific antibodies. The main risk of these diseases is severe brain damage or death due to intracranial hemorrhage. Prevention and screening are difficult because of the lack of predicting factors. Only some women are at high risk of fetal thrombocytopenia (HLA DRW 52a HPA-la negative women or women with a previous history of immune thrombocytopenic purpura and having platelet-specific autoantibodies). Antenatal diagnosis and therapy have altered the natural course of fetal alloimmune thrombocytopenia. No prenatal treatment has proved to be effective in autoimmune thrombocytopenia and prenatal diagnosis by fetal blood sampling is controversial. A better knowledge of the pathogenesis of gestational incidental thrombocytopenia in otherwise healthy pregnancies, could define a group at high risk of fetal thrombocytopenia.

Algorithms↗
PubMed1996

[Management of pregnant women with abnormal cervical smears. A series of 146 patients].

OBJECTIVES: Evaluation of the value of colposcopy and directed biopsy in the follow-up of pregnant women presenting with abnormal cervical smear. MATERIAL AND METHODS: Retrospective study of 146 patients examined by colposcopy during pregnancy between January 1985 and December 1994. RESULTS: Colposcopy was satisfactory in 86% of patients. Colposcopic impression was concordant with the final diagnosis, overestimated and underestimated in 69%, 18% and 13% of the cases, respectively. Directed biopsies were performed in 115 patients. In one case, bleeding necessitated vaginal packing for 24 hours. Directed biopsy correlated well with the final diagnosis in 87% of low grade CIN and in 90% of high grade CIN. In 4 patients, conisation was performed between 10 and 16 weeks of gestation without subsequent obstetrical complications. CONCLUSION: Colposcopy with directed biopsy is a reliable tool to evaluate abnormal smear during pregnancy.

Adolescent↗
PubMed1996

[Management of hematologic malignancies during pregnancy].

Hodgkin's disease, non-Hodgkin lymphoma or leukemia occurring in a pregnant patient is a rare event. Diagnosis of hematologic malignancies in a pregnant woman usually poses a quandrum of psychological, ethical and medical considerations. All of these situations require a multidisciplinary team. Adequate staging and treatment of hematologic malignancies are complicated by the pregnancy. In the first trimester, termination of the pregnancy should be considered in order to provide the best outcome for the woman and fetus. In this review we have focused on the use of chemotherapy for the pregnant patient. This review reveals that the use of chemotherapy resulted in both objective disease remissions and the subsequent delivery of normal infant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Transcribing of Escherichia coli genes with mutant T7 RNA polymerases: stability of lacZ mRNA inversely correlates with polymerase speed.

When in Escherichia coli the host RNA polymerase is replaced by the 8-fold faster bacteriophage T7 enzyme for transcription of the lacZ gene, the beta-galactosidase yield per transcript drops as a result of transcript destabilization. We have measured the beta-galactosidase yield per transcript from T7 RNA polymerase mutants that exhibit a reduced elongation speed in vitro. Aside from very slow mutants that were not sufficiently processive to transcribe the lacZ gene, the lower the polymerase speed, the higher the beta-galactosidase yield per transcript. In particular, a mutant which was 2.7-fold slower than the wild-type enzyme yielded 3.4- to 4.6-fold more beta-galactosidase per transcript. These differences in yield vanished in the presence of the rne-50 mutation and therefore reflect the unequal sensitivity of the transcripts to RNase E. We propose that the instability of the T7 RNA polymerase transcripts stems from the unmasking of an RNase E-sensitive site(s) between the polymerase and the leading ribosome: the faster the polymerase, the longer the lag between the synthesis of this site(s) and its shielding by ribosomes, and the lower the transcript stability.

Blotting, Northern↗
PubMed1995

The Ser 460 to Pro substitution of the protein S alpha (PROS1) gene is a frequent mutation associated with free protein S (type IIa) deficiency.

A Ser 460 to Pro mutation of protein S (PS), involving a T to C transition in exon XIII of the protein S alpha (PROS1) gene and known as the Heerlen polymorphism, was found in 16 of 85 symptomatic patients with PS deficiency (18.8%) and only 1 of 113 healthy subjects (0.8%). Another frequent polymorphism was described in exon XV of the PROS1 gene, in the codon for Pro 626 (CCA/CCG). We found that Heerlen polymorphism was associated with allele CCA and not with allele CCG, suggesting a probable transmission by a common ancestor. Most subjects bearing the Ser 460 to Pro mutation were deficient in free PS, but had normal total PS levels. Normal levels of the C4b-binding protein (C4b-BP) isoform containing a beta chain (C4b-BP beta +) ruled out increased C4b-BP beta + as a cause of the free-PS deficiency. The binding curves of the mutated (Heerlen) PS on C4b-BP immobilized on microplates were biphasic, suggesting that one molecule of C4b-BP can bind two molecules of Heerlen PS. Because normal PS binds to C4b-BP with 1:1 stoichiometry, this may explain the free-PS deficiency observed in patients carrying the Ser 460 to Pro mutation.

Carrier Proteins↗
PubMed1995

The stability of Escherichia coli lacZ mRNA depends upon the simultaneity of its synthesis and translation.

We have used either Escherichia coli or T7 RNA polymerase to transcribe in E. coli a series of lacZ genes that differ in the nature of their ribosome binding sites (RBS). Each T7 RNA polymerase transcript yields from 15- to 450-fold less beta-galactosidase than its E. coli polymerase counterpart, the ratio being larger when weaker RBS are used. The low beta-galactosidase yield from T7 transcripts reflects their low stability: the ams-1/rne-50 mutation, which inactivates RNase E, nearly equalizes the beta-galactosidase yields from T7 and E. coli RNA polymerase transcripts. T7 RNA polymerase transcribes the lacZ gene approximately 8-fold faster than the E. coli enzyme. We propose that this higher speed unmasks an RNase E cleavage site which is normally shielded by ribosomes soon after its synthesis when the slower E. coli enzyme is used. This leads to degradation of the T7 transcript, unless the leading ribosome comes in time to shield the cleavage site: the weaker the RBS, the lower this probability and the more severe the inability of T7 RNA polymerase transcripts for beta-galactosidase synthesis.

Base Sequence↗
PubMed1995

Identification of 15 different candidate causal point mutations and three polymorphisms in 19 patients with protein S deficiency using a scanning method for the analysis of the protein S active gene.

To screen for point mutations causing protein S deficiency, we used a sequence of techniques specifically for the study of the protein S active gene, PS alpha. This strategy comprises amplification of exons and intron/exon junctions by means of the polymerase chain reaction (PCR) and electrophoresis of the amplified fragments in polyacrylamide gel containing a gradient of denaturing agents (denaturing gradient gel electrophoresis). Only fragments with altered melting behavior are sequenced after asymmetric PCR. Beside the frequent polymorphism already described on Pro 626, we detected 18 different sequence variations by studying exons II, IV, V, VIII, X, and XV in 19 of 100 consecutive patients with protein S deficiency. Fifteen were candidate causal mutations, 4 of which were associated with a qualitative deficiency (type IIa or IIb). The remaining three sequence variations were probably polymorphisms.

Base Sequence↗
PubMed1995

Recombinant hirudin (HBW 023): biological data of ten patients with severe venous thrombo-embolism.

This study reports on the biological data of ten patients with acute venous thrombo-embolism. They were treated for 5 days with continuous intravenous infusion of a fixed dose (0.05 mg/kg/hr) of a recombinant hirudin (r-H HBW 023 Behringwerke, Germany). The plasma level of r-H (HBW 023), assessed by an anti-factor IIa amidolytic activity, was stable after Day 2 and showed considerable individual variations. It correlated with APTT ratio, suggesting that this test is a reliable tool to monitor therapy. In contrast, thrombin time was constantly over 120 sec (control 15 sec) and consequently was not a useful parameter. Prothrombin time showed a slight, but significant, prolongation, which was correlated with the increase of APTT ratio. There was no bleeding time prolongation, platelet count, or ATIII level decrease. Levels of thrombin-antithrombin III complexes, and D-dimers, which were high in all patients on admission, decreased during the course of the treatment but remained abnormal on Day 5, showing an ongoing hemostasis and fibrinolysis activation: this is consistent with the delayed, but only slightly decreased thrombin generation evidenced by thrombin generation test performed on Day 3. These results suggest that thrombin inhibition by rH-hirudin at this dosage is only partial, which allows the generation of traces of thrombin needed for the feed-back thrombin production generated by factor V and VIII activation.

Adult↗
PubMed1995

Cervical cancer screening with cervicography and cytology.

The results of colposcopy and directed biopsies were compared with the cytological findings and cervicography in 1539 asymptomatic outpatients undergoing routine cervical cancer screening in order to compare the accuracy of cervicography and cytology and to assess the potential benefits of the combination of both screening tests. With the new reporting criteria, cervicography looked less sensitive (53% vs. 56%; P = 0.718) and significantly less specific (97% vs. 98%; P = 0.040) than cytology. In comparison with cytology and at the expense of a recall rate of 9%, the combination of both screening tests and to an increase of the sensitivity (77% vs. 56%; P = 0.013) but also to a decrease of the specificity (95% vs. 98%; P < 0.0001) and of the positive predictive value (44% vs. 60%; P = 0.051). When the original reporting criteria were applied to cervicography, the combination of both screening tests led to optimal sensitivity and negative predictive value (100%, respectively) at the expense of an unrealistic recall rate of 20%. Consequently, cervicography should not be considered as an alternative to cytology for cervical cancer screening since its accuracy is not significantly better and its rate of technically defective tests is significantly higher. The combination of both methods increases the sensitivity of cervical cancer screening at the expense of a high recall rate, of which cost effectiveness has to be assessed.

Adolescent↗
PubMed1995

Seric and local antibodies against a synthetic peptide of HPV16.

An ELISA method was used to detect IgG and IgA directed against a synthetic peptide derived from the E2 ORF of the human papillomavirus (HPV) 16 in sera and in cervico-vaginal secretions from 20 women without evidence of HPV infection and from 41 women with histological diagnosis of HPV infection. The proportion of IgA positive sera (63.4% in the case-group vs. 20.0% in the control-group) and secretions (48.8% in the case-group vs. 15.0% in the control-group) was significantly higher in women with HPV infection and seemed to increase with the severity of the cervical lesion. Such a difference was not found for specific IgG. Comparing, for each patient, the antibody level in the serum and in the secretions, we found that the amount of IgA was at mean 2.4 times higher in the sera than in the secretions.

Adult↗