Prostaglandin E2 mid-trimester evacuation of the uterus for women with a previous cesarean section.
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Abortion, Induced↗
Biomedical subjects
M Cohen
Publications and source records attributed to M Cohen.
Status of p53 in first-trimester cytotrophoblastic cells.
p53 has been called the cellular gatekeeper of the genome because it can induce cell-cycle arrest in G1, apoptosis or affect DNA replication in response to DNA damage. As p53 has been observed in first-trimester cytotrophoblastic cells (CTB), but its expression in normal cells is generally not detectable because of its short half-life, p53 could play an important role in cellular differentiation and/or in the control of the invasion of trophoblastic cells; therefore, p53 status was investigated in these cells. Using different antibodies recognizing different epitopes of p53 protein, abundant p53 expression was observed both in nuclear and in cytoplasmic compartments of first-trimester CTB. Whereas p53 was detected in the nuclei of few trophoblastic cells with an antibody recognizing the N-terminal epitope of the protein, high expression level of p53 in the cytoplasm of CTB was detected with an antibody recognizing the middle part of p53. The lack of immunoreactivity of p53 with antibodies recognizing the epitopes located at the N-terminus of p53 and the high level of p53 protein observed in the cytoplasm of CTB suggest that the N-terminus of p53 is involved in the formation of complexes. These cytoplasmic complexes were detected under non-reducing conditions in western blot analysis and had apparent molecular weights (MW) of 195, 167 or 125 kDa. These complexes could prolong the half-life of p53 in the cytoplasm of CTBs. By contrast, in the nuclei of CTBs, p53 seems to be present as a tetramer.
Cells, Cultured↗
Binding hot spots in the TEM1-BLIP interface in light of its modular architecture.
Proteins bind one another in aqua's solution to form tight and specific complexes. Previously we have shown that this is achieved through the modular architecture of the interaction network formed by the interface residues, where tight cooperative interactions are found within modules but not between them. Here we extend this study to cover the entire interface of TEM1 beta-lactamase and its protein inhibitor BLIP using an improved method for deriving interaction maps based on REDUCE to add hydrogen atoms and then by evaluating the interactions using modifications of the programs PROBE, NCI and PARE. An extensive mutagenesis study of the interface residues indeed showed that each module is energetically independent on other modules, and that cooperativity is found only within a module. By solving the X-ray structure of two interface mutations affecting two different modules, we demonstrated that protein-protein binding occur via the structural reorganization of the binding modules, either by a "lock and key" or an induced fit mechanism. To explain the cooperativity within a module, we performed multiple-mutant cycle analysis of cluster 2 resulting in a high-resolution energy map of this module. Mutant studies are usually done in reference to alanine, which can be regarded as a deletion of a side-chain. However, from a biological perspective, there is a major interest to understand non-Ala substitutions, as they are most common. Using X-ray crystallography and multiple-mutant cycle analysis we demonstrated the added complexity in understanding non-Ala mutations. Here, a double mutation replacing the wild-type Glu,Tyr to Tyr,Asn on TEM1 (res id 104,105) caused a major backbone structural rearrangement of BLIP, changing the composition of two modules but not of other modules within the interface. This shows the robustness of the modular approach, yet demonstrates the complexity of in silico protein design.
Alanine↗
Indications for familial screening and gonadectomy in patients with 46,XY gonadal dysgenesis.
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Adolescent↗
Post-mortem fetal MRI: what do we learn from it?
Post-mortem magnetic resonance (MR) imaging is of increasing interest not only as an alternative to autopsy but as a research tool to aid the interpretation and diagnosis of in utero MR images. The information from the post-mortem MR has allowed the development of imaging sequences applicable to in utero imaging and neonatal imaging. It has established brain development during gestation and has provided data on this to which in utero MR can be compared. The detail available from the post-mortem images is such that brain development can be studied in a non-invasive manner, a permanent record on the normal and abnormal areas is available and a greater understanding of developmental abnormalities is possible.
Autopsy↗
A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours.
This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m(-2) DL), combined with cisplatin (standard dose 75 mg m(-2)). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m(-2) DL; at the 110 mg m(-2) DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m(-2), but not through the 150 mg m(-2) DL. The mean+/-SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317+/-60 ml min(-1) m(-2), 258+/-96 l m(-2) and 30.8+/-7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m(-2) (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m(-2).
Adult↗
Post-mortem MRI of the foetal spine and spinal cord.
AIMS: To compare the findings of post-mortem magnetic resonance imaging (MRI) of the foetal spine with autopsy with a view to using post-mortem MRI as an alternative or adjunct to autopsy, particularly in foetal and neonatal cases. MATERIALS AND METHODS: The brains and spines of 41 foetuses, with a gestational age range of 14-41 weeks, underwent post-mortem MRI before autopsy. Post-mortem MRI of the brain consisted of T2-weighted sequences in three orthogonal planes and MRI of the spine consisted of T2-weighted sequence in the sagittal and axial planes in all cases and coronal planes in selected cases. RESULTS: Thirty of 41 (78%) foetal spines were found to be normal at autopsy and on post-mortem MRI. Eleven of 41 (22%) foetal spines were abnormal: eight foetuses had myelomeningocoeles and Chiari 2 deformities, one foetus had limited dorsal myeloschisis, one foetus had caudal regression syndrome, and one had diastematomyelia. The post-mortem MRI findings concurred with the autopsy findings in 10/11 of the abnormal cases, the disagreement being the case of diastematomyelia that was shown on post-mortem MRI but was not diagnosed at autopsy. CONCLUSIONS: In this series, post-mortem MRI findings agreed with the autopsy findings in 40/41(98%) cases and in one case the post-mortem MRI demonstrated an abnormality not demonstrated at autopsy.
Autopsy↗
[Subungual glomus tumors of the fingers: ultrasound diagnosis].
INTRODUCTION: Glomus tumors of the fingers are rare, benign tumors. These lesions are hamartomas, originating from dermoepidermic glomus, most commonly located at the distal phalanx, and in particular under the nail. Diagnosis is often delayed because of the absence of specific symptoms. Confirmation can only be made by histological study. The aim of this retrospective study is to define the role of ultrasound examination in the diagnosis of glomus tumors of the fingers. METHOD: During the period March 2002-March 2004, 12 cases of subungueal glomus tumors were included in this retrospective study. All patients underwent ultrasound and Doppler examinations before surgery. All Ultrasound Doppler studies were performed by the same radiologist. The mean age of patients was 44 year-old and the sex-ratio was 1/2. RESULTS: Pain was noted as a symptom in all patients. The mean size of the tumor was 3.5 mm. In eleven patients, ultrasound study was able to confirm the diagnosis, but it failed in one case because of the small size of the tumor (less than 2 mm). Ten tumors presented a Doppler hypersignal, located in the tumor and compatible with the diagnosis of glomus tumor. DISCUSSION: Diagnosis of glomus tumor is based on clinical examination, standard radiology, and ultrasound Doppler study. Ultrasound examination and Doppler study gives better visualization of tumors compared to standard radiology. These studies are useful for follow-up of patients in the post-operative period.
Adult↗
[Accidental exposure to blood by midwives in French maternity units: results of the national surveillance 2003].
OBJECTIVE: Midwives appear to be the health care workers exposed to the highest rates of bloodborne injury. In this paper - based on a national survey - we describe the bloodborne injuries occurring in this profession. MATERIAL AND METHOD: During the year 2003, 241 hospitals took part in a national survey of bloodborne injuries. Employees registered anonymous standardized reports of bloodborne events with the Occupational Medicine Unit. The data were processed by the coordination center for the fight against nosocomial infections (C. CLIN) which is in charge of the national analysis of all the events reported in this database. RESULTS: 169 of the 6973 bloodborne events reported during 2003 (2.4%), were signed by midwives or midwife students. The first three most frequent accidents reported were: ocular projections during childbirth, pricks when repairing episiotomy, pricks or cuts when handling soiled instruments. CONCLUSION: Improving knowledge of risk as well as promotion of protection/prevention measures well adapted to this profession should be helpful in optimizing future attitudes.
Adult↗
Subcapsular haematoma and multifocal necrosis as fatal liver complications following umbilical vein catheterisation in a premature baby.
We describe a case of subcapsular haematoma of the right lobe (SHL) and multifocal necrosis of the left lobe (MNL) of the liver following umbilical vein catheterisation (UVC) in a female at 24 weeks' gestation. SHL and MNL have been described as uncommon complications following umbilical vein catheterisation. To our knowledge this is the first time both complications have developed in the same patient. SHL should be considered in the differential diagnosis of hypovolaemic shock in this group of patients.
Catheterization↗
Two lucky escapes-placenta previa.
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Adult↗
Sacral stress fracture: an unusual cause of low back pain in an amateur tennis player.
Stress fractures are common in athletes, and their incidence in sport is estimated at 2-4%. A case is reported of a stress fracture of the sacrum in an amateur tennis player. The patient was treated with rest and physiotherapy, focusing on stretching programmes and analgesic treatments, followed by an educational programme of tennis training and muscle strengthening. This appears to be the first report of this pathology in a tennis player.
Fractures, Stress↗
Proof of partial imbalances 6q and 11q due to maternal complex balanced translocation analyzed by microdissection of multicolor labeled chromosomes (FISH-MD) in a patient with Dandy-Walker variant.
We report on a family in which a daughter is described with mental retardation, as well as malformations of the heart, and of the brain (Dandy-Walker variant). The patient's phenotype suggests a chromosomal rearrangement. However, her karyotype was unremarkable by conventional cytogenetic analysis. In order to detect chromosome rearrangements overseen by this method, the subtelomere regions of suspicious chromosomes were verified by fluorescence in situ hybridization (FISH). A rearranged derivative chromosome 6 was identified. Further examinations by FISH-microdissection (FISH-MD) revealed a maternal complex balanced translocation. The patient inherited the derivative chromosome 6 from her mother and therefore carries a partial monosomy 6q26-->qter and a partial trisomy 11q23.3-->qter.
Allelic Imbalance↗
Metalloproteinases and human placental invasiveness.
Matrix metalloproteinases (MMPs) are the main mediators of extracellular matrix degradation. This confers an important role to these enzymes in the invasion of the trophoblast cells where their expression are spatiotemporally regulated. The regulation of MMPs activity is complex and is established at different levels. Their expressions depend on various cis-elements in their gene promoter, and are induced or repressed by various soluble factors. After expression and secretion, the proMMPs must be activated through an activation network. Then, the enzyme activity is regulated by inhibition or stabilization. In this review, we shall focus on the expression, the role in invasion and the regulation of MMPs in the human placenta.
Cell Adhesion↗
Additional anti-Gram-positive antibiotic treatment for febrile neutropenic cancer patients.
BACKGROUND: The pattern of infections among neutropenic cancer patients has shifted in the last decades to a predominance of Gram-positive infections. Some of these Gram-positive bacteria are increasingly resistant to beta-lactams and necessitate specific antibiotic treatment. OBJECTIVES: To assess the effectiveness of empirical anti-Gram-positive (antiGP) antibiotic treatment for febrile neutropenic cancer patients in terms of mortality and treatment failure. To assess the rate of resistance development, further infections and adverse events associated with additional antiGP treatment. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to 2004), EMBASE (January 1980 to 2004), LILACS (1982 to 2004), conference proceedings, and all references of included studies. First authors of all included and potentially relevant trials were contacted. SELECTION CRITERIA: Randomised controlled trials comparing one antibiotic regimen to the same regimen with the addition of an antiGP antibiotic for the treatment of febrile neutropenic cancer patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and extracted all data. Relative risks (RR) with 95% confidence intervals (CI) were calculated. A random effects model was used for all comparisons showing substantial heterogeneity (I(2 )> 50%). Outcomes were extracted by intention-to-treat and the analysis was patient-based whenever possible. MAIN RESULTS: Thirteen trials and 2392 patients or episodes were included. Empirical antiGP antibiotics were tested at the onset of treatment in eleven studies and for persistent fever in two studies. The antiGP treatment was a glycopeptide in nine trials. Seven studies were assessed in the overall mortality comparison and no significant difference between the comparator arms was seen, RR 0.82 (95% CI 0.56 to 1.20, 852 patients). Ten trials assessed failure including modifications as failures, while six assessed overall failure, disregarding treatment modifications. Failure with modifications was significantly reduced, RR 0.76 (95% CI 0.68 to 0.85, 1779 patients) while overall failure was equal, RR 1.00, 95% CI (0.79 to 1.27, 943 patients). Both mortality and failure did not differ significantly among patients with Gram-positive infections, but comparisons were small. Data regarding other patient subgroups likely to benefit from antiGP treatment were not available. Glycopeptides did not increase fungal superinfection rates, and were associated with a reduction in documented Gram-positive superinfections. Resistant colonisation was not documented in the studies. AUTHORS' CONCLUSIONS: Current evidence shows that the addition of antiGP treatment, namely glycopeptides, prior to documentation of a Gram-positive infection does not improve outcomes.
Anti-Bacterial Agents↗
Breakpoints around the HOXD cluster result in various limb malformations.
BACKGROUND: Characterisation of disease associated balanced chromosome rearrangements is a promising starting point in the search for candidate genes and regulatory elements. METHODS: We have identified and investigated three patients with limb abnormalities and breakpoints involving chromosome 2q31. Patient 1 with severe brachydactyly and syndactyly, mental retardation, hypoplasia of the cerebellum, scoliosis, and ectopic anus, carries a balanced t(2;10)(q31.1;q26.3) translocation. Patient 2, with translocation t(2;10)(q31.1;q23.33), has aplasia of the ulna, shortening of the radius, finger anomalies, and scoliosis. Patient 3 carries a pericentric inversion of chromosome 2, inv(2)(p15q31). Her phenotype is characterised by bilateral aplasia of the fibula and the radius, bilateral hypoplasia of the ulna, unossified carpal bones, and hypoplasia and dislocation of both tibiae. RESULTS: By fluorescence in situ hybridisation, we have mapped the breakpoints to intervals of approximately 170 kb or less. None of the three 2q31 breakpoints, which all mapped close to the HOXD cluster, disrupted any known genes. CONCLUSIONS: Hoxd gene expression in the mouse is regulated by cis-acting DNA elements acting over distances of several hundred kilobases. Moreover, Hoxd genes play an established role in bone development. It is therefore very likely that the three rearrangements disturb normal HOXD gene regulation by position effects.
Adolescent↗
Interventions for treating posterior cruciate ligament injuries of the knee in adults.
BACKGROUND: Injuries of the posterior cruciate ligament (PCL) of the knee frequently occur in automobile accidents and sports injuries, although they are less frequent overall than injuries of the anterior cruciate ligament (ACL). Some patients show significant symptoms and subsequent articular deterioration, while others are essentially asymptomatic, maintaining habitual function. Management of PCL injuries remains controversial and prognosis can vary widely. Interventions extend from non-operative (conservative) procedures to reconstruction of the PCL, in the hope that the surgical procedure may have a positive effect in the reduction/prevention of future osteoarthritic changes in the knee. OBJECTIVES: To determine the effectiveness and safety of surgical and conservative interventions for PCL injuries in adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register (April 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE via PubMed (1966 to April 2004), EMBASE (1966 to April 2004), CINAHL (1982 to April 2004), LILACS (1982 to April 2004), SportsDiscus (1975 to April 2004), and reference lists of articles. SELECTION CRITERIA: Randomized or quasi-randomized clinical trials comparing various methods of operative and conservative interventions, and comparisons with each other for the treatment of PCL injuries. DATA COLLECTION AND ANALYSIS: References found with the search strategy were evaluated independently by two review authors. MAIN RESULTS: No randomized or quasi-randomized controlled studies meeting the selection criteria were identified. AUTHORS' CONCLUSIONS: Future research should include randomized controlled trials of acute isolated PCL injuries, or PCL injuries when combined with other ligament injuries of the knee, treated operatively and conservatively. Adequate numbers of patients and an objective methodology for patient evaluation must be used in future studies of these interventions to determine the long-term results.
Adult↗
Electromyography as a measure of peak and cumulative workload in intermediate care and its relationship to musculoskeletal injury: an exploratory ergonomic study.
Injury rates in Intermediate Care (IC) facilities are high and the factors related to these injuries are unclear. The objectives of this exploratory sub-study, which is part of a large multi-faceted study in 8 IC facilities are to: (1) evaluate EMG measured over a full-shift in the back and shoulders of 32 care aides (CAs) as an indicator of peak and cumulative workload (n = 4 x 8 facilities); investigate the relationship between EMG measures and injury indicators; and explore the relationship between EMG measures and other workload measurements. Lumbar EMG was converted to predicted cumulative spinal compression and ranged in CAs from 11.7 to 22.8 MNs with a mean of 16.4 MNs. Average compression was significantly different during different periods of the day (p < 0.001) with highest compression during pre-breakfast when CAs assist most with activities of daily living. Significant differences were found in average compression between low and high injury facilities for 3 of 5 periods of the day (p < 0.010). Peak compressions exceeding 3400 N occurred for very little of the workday (e.g. 11.25s during the 75 min period pre-breakfast). Peak neck/shoulder muscle activity is low (99% APDF ranged from 8.33% to 28% MVC). Peak and cumulative spinal compression were significantly correlated with lost-time and musculoskeletal injury rates as well as with total tasks observed in the CAs (p < 0.01). Perceived exertion was only correlated with peak compressions (p < 0.01). Facilities with low injury rates provided significantly more CAs (p < 0.01) to meet resident needs, and subsequently CAs performed fewer tasks, resulting in less peak and cumulative spinal loading over the day.
Back↗