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Biomedical subjects

E Martin

Publications and source records attributed to E Martin.

At least 37 records · Page 2Linked to original sources

Mutation and methylation analysis of TP53 in adrenal carcinogenesis.

AIM: To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. METHODS: Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue samples were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by polymerase chain amplification using intronic primers for exons 2-11 and direct sequencing of the product. In 10 ACCs and five normal adrenal tissue specimens, methylation of the 16 CpG sites within the TP53 promoter was examined using bisulphite methylation sequencing. RESULTS: Coding region mutation in TP53 was demonstrated in 5 of 20 ACCs. There were four mis-sense mutations and one frameshift mutation. Four of 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter and 3 of 4 died of disease within 12 months of surgical resection. No methylation was seen in the TP53 promoter in 10 ACC and the five normal adrenal tissues examined. CONCLUSION: Coding region mutation in TP53 occurs in 25% of ACCs with a trend toward a poorer prognosis. Promoter methylation of TP53 is not present in ACC as a mechanism for tumour suppressor gene (TSG) inactivation and, therefore, other genes in the 17p13 region are implicated in adrenal carcinogenesis.

Adrenal Gland Neoplasms↗

Recombinant human antithrombin III restores heparin responsiveness and decreases activation of coagulation in heparin-resistant patients during cardiopulmonary bypass.

OBJECTIVES: We sought to evaluate the efficacy of recombinant human antithrombin III for restoration of heparin responsiveness in heparin-resistant patients scheduled for cardiac surgery. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing elective cardiac surgery. Patients were considered heparin resistant if the activated clotting time was less than 480 seconds after 400 U/kg heparin. Fifty-two heparin-resistant patients were randomized into 2 cohorts. One cohort received a single bolus (75 U/kg) of recombinant human antithrombin III (n = 28), and the other, the placebo group (n = 24), received a normal saline bolus. If the activated clotting time remained less than 480 seconds, this was defined as treatment failure, and 2 units of fresh frozen plasma were transfused. Patients were monitored for adverse events during hospitalization. RESULTS: Six (21%) of the patients in the recombinant human antithrombin III group received fresh frozen plasma transfusions compared with 22 (92%) of the placebo-treated patients ( P < .001). Two units of fresh frozen plasma did not restore heparin responsiveness. There was no increased incidence of adverse events associated with recombinant human antithrombin III administration. Postoperative 24-hour chest tube bleeding was not different in the 2 groups. Surrogate measures of hemostatic activation suggested that there was less activation of the hemostatic system during cardiopulmonary bypass in the recombinant human antithrombin III group. CONCLUSION: Treatment with recombinant human antithrombin III in a dose of 75 U/kg is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation for cardiopulmonary bypass in the majority of heparin-resistant patients. Two units of fresh frozen plasma were insufficient to restore heparin responsiveness. There was no apparent increase in bleeding associated with recombinant human antithrombin III.

Adult↗

[Five-year survival of Ile-de-France cancer patients diagnosed in 1994].

BACKGROUND: This study aimed to estimate survival at 5 years by localization, sex and stage of the patients who presented a new cancer in 1994 in the Ile-de-France area. METHODS: A cohort study began in 1994 by an exhaustive collection of the incidental cancers notified in the Ile-de-France area at the health insurance (27,080 patients). A stratified random sample based on tumor localization was followed at 1 year, 3 years and 5 years. The analysis of the observed survival was carried out according to Kaplan-Meier method. Relative survival was calculated according to Ederer II method. RESULTS: The follow-up sample concerned 4,166 patients. For all cancers, relative survival at 5 years was 65% for the women and 51% for the men. Relative survival rate at 5 years was 82% for the women with a breast cancer (98% for the patients in stage I) and 66% for those with a cancer of the cervix. Relative survival at 5 years for colonic cancer was 67% for men and 54% for women. For lung cancer, the relative survival rate fell from 47% for patients in stage I to 5% for those in stage IV. CONCLUSION: Our study produces population-based survival data for a entire geographical area covering 20% of the French population. Survival improves with earlier diagnosis but depends also on quality of care and availability of care: access to medical care can be a favouring factor. While in terms of incidence the situation in the Ile-de-France area is close to the national situation, survival at 5 years for a set of tumors appears to be better in this area than the nationwide figures. Besides providing information useful to determine mortality and incidence, the health insurance data offer additional insight to cancer epidemiology and contribute to better knowledge of this disease.

Breast Neoplasms↗

Marchiafava-Bignami-like injury of the corpus callosum in an infant.

We report on a 16-month-old boy who presented with truncal ataxia and intermittent nystagmus. Magnetic resonance imaging (MRI) at 19 months showed a T (2)-hyperintensity of the splenium and the genu of the corpus callosum with extension into the adjacent frontal white matter. Diffusion tensor imaging (DTI) revealed a corresponding area of restricted diffusion, suggesting cytotoxic oedema. The extent and localisation of the signal abnormalities mimic tissue injury as seen in Marchiafava-Bignami disease (MBD). Metabolic investigations were normal. Follow-up imaging at 24 months showed a similar T (2)-hyperintensity of the corpus callosum and white matter while on DTI the cytotoxic oedema had resolved. Clinically a remaining truncal and gait ataxia, clumsiness and a developmental delay is seen. Goal of this case report is (a) to present a rare case of Marchiafava-Bignami-like injury of the corpus callosum in an infant and (b) to discuss the neuroradiological imaging findings including MRI and DTI.

Corpus Callosum↗

Association between early postoperative coagulation activation and peri-operative myocardial ischaemia in patients undergoing vascular surgery.

We investigated the association of peri-operative myocardial ischaemia with activation of coagulation and endogenous fibrinolysis in patients undergoing vascular surgery. In 50 patients, continuous Holter monitoring was performed to assess peri-operative myocardial ischaemia and 12-lead electrocardiography was recorded preoperatively and 72 h postoperatively to assess myocardial infarction. Serial blood samples were drawn peri-operatively to determine the concentrations of fibrin monomers (for activation of coagulation), D-dimer (for endogenous fibrinolysis) and cardiac troponin T and I. Patients with myocardial ischaemia showed higher concentrations of fibrin monomers at 48 h, and higher concentrations of d-dimer preoperatively and at 24 and 48 h postoperatively. In patients with peri-operative myocardial ischaemia, strong positive correlations were observed between fibrin monomer and D-dimer concentrations at 15 min and 4 h postoperatively, and cardiac troponins at 15 min and at 4, 24, 48 and 72 h postoperatively. Early postoperative activation of coagulation and fibrinolysis is associated with peri-operative myocardial cell damage among patients who are at risk for, or have a history of, coronary artery disease plus peri-operative myocardial ischaemia.

Aged↗

Peritoneal folds of the rabbit (Oryctolagus cuniculus).

The anatomy of the rabbit is not well known and there is no consensus on the anatomical nomenclature for this species. The objective of this study was to give a complementary description of the peritoneal folds in order to improve the existing knowledge on this species. Eighteen adult rabbits were studied. Ten animals were dissected unfixed and the remaining eight after fixation in formalin. The hepatic ligaments were similar to those of the dog. The transverse mesocolon was absent. The entry to the caudal recess of the omental sac was relatively smaller than that in other domestic species. We consistently found an omental foramen. An amount of fat tissue was almost always found in the proximal mesorchium. The vaginal process was inconstant.

Animals↗

Prevalence of victims of violence admitted to an emergency department.

OBJECTIVE: To collect data on the consultation frequency and demographic profile of victims of violence attending an emergency department (ED) in Switzerland. METHODS: We undertook screening of all admitted adult patients (>16 years) in the ED of the CHUV, Lausanne, Switzerland, over a 1 month period, using a modified version of the Partner Violence Screen questionnaire. Exclusionary criteria were: life threatening injury (National Advisory Committee on Aeronautics score > or =4), or inability to understand or speak French, to give oral informed consent, or to be questioned without a family member or accompanying person being present. Data were collected on history of physical and/or psychological violence during the previous 12 months, the type of violence experienced by the patient, and if violence was the reason for the current consultation. Sociodemographic data were obtained from the registration documents. RESULTS: The final sample consisted of 1602 patients (participation rate of 77.2%), with a refusal rate of 1.1%. Violence during the past 12 months was reported by 11.4% of patients. Of the total sample, 25% stated that violence was the reason for the current consultation; of these, 95% of patients were confirmed as victims of violence by the ED physicians. Patients reporting violence were more likely to be young and separated from their partner. Men were more likely to be victims of public violence and women more commonly victims of domestic violence. CONCLUSIONS: Based on this monthly prevalence rate, we estimate that over 3000 adults affected by violence consult our ED per annum. This underlines the importance of the problem and the need to address it. Health services organisations should establish measures to improve quality of care for victims. Guidelines and educational programmes for nurses and physicians should be developed in order to enhance providers' skills and basic knowledge of all types of violence, how to recognise and interact appropriately with victims, and where to refer these patients for follow up care in their local networks.

Adolescent↗

Drug hypersensitivity: insights into pathomechanisms.

In adverse reactions to drugs with an immunological basis (ADRIB) specific IgE antibodies or sensitised effector T cells take part. Each type of response induces well defined clinical entities. For T cell reactions, classically known as Type IV Gel and Coomb responses, different subtypes have been classified. These correspond to different clinical entitles and each have characteristically histopathological findings. Advanced in vitro studies by development of T cell liens and T cell clones to different drugs compounds and the monitorisation of the immunological response during the course of these diseases has provided new insights for a better understanding and evaluation of ADRIB.

Chemotaxis, Leukocyte↗

Amyloid precursor protein (APP) and its derivatives change after cellular energy depletion. An in vitro-study.

To study the relationship between the metabolism of amyloid precursor protein (APP) and cellular energy failure, HEK 293 cells stably transfected with betaAPP 695 underwent graded energy failure induced either by i) hypoxia (pO(2) 25 mm Hg), ii) inhibition of the respiratory chain by sodium azide (NaN(3)), or iii) by combined glucose deprivation/hypoxia of different duration and severity. Secreted APP (APPs) and the derivative betaA4 were quantified autoradiographically by immunoprecipitation, and [(35)S] methionine labeling. APP holoprotein (APPh) was determined by Western blot analysis. The concentrations of the energy-rich metabolites ATP, ADP, creatine phosphate (CrP), and adenosine were measured by high performance liquid chromatography. Mild to moderate energy failure after NaN(3) treatment (2h, 4h) and hypoxia (2h, 8h) was characterized by normal ATP concentration but also by a high reduction in CrP. A stress condition indicated by an increased ATP turnover and adenosine increase was obtained. Intracellular APPh increased but its metabolites APPs and betaA4 as measured in the extracellular compartment decreased. These changes may point to a compensatory response of APP but also to a initial disturbance in intracellular APP metabolism. Severe abnormalities in both energy formation and utilization after 8h NaN(3) and hypoxia glucose deprivation were found to be accompanied by a drastic fall in intracellular APPh concentration by at least 50%, paralleled by an accelerating reduction in the extracellular concentrations of both APPs and betaA4.A significant linear correlation between APPh and ATP and between CrP and betaA4 became obvious. The data of the present study indicate that abnormalities in APP metabolism were generated in an energy-dependent manner. The obvious similarities to sporadic Alzheimer s disease are discussed.

Amyloid beta-Protein Precursor↗

Fast quantitative diffusion-tensor imaging of cerebral white matter from the neonatal period to adolescence.

We investigated the isotropic diffusion coefficient (D') and fractional anisotropy (FA) in white matter (WM) during brain development, using an optimised diffusion-tensor imaging (DTI) method with whole brain coverage in a clinically acceptable time. We images 52 children with no evident neurological abnormality (30 boys, 22 girls aged 1 day-16 years) using high-angle DTI with optimised temporal gradient performance. D' and FA were calculated in 10 regions of interest in white matter. We saw that the age-related reduction in D' and increase in FA follow a mono- or biexponential model in white matter, probably depending on the compactness and myelination rate of the fibre tracts. In contrast to other areas, in which adult values were reached during the third year, there is a trend to continuous increase in FA in all deep white-matter areas, suggesting continuing maturation and organisation of deep tracts not detected on conventional MRI.

Adolescent↗

[Role of the innate immune response in sepsis].

The innate immune system succeeds against the majority of infections before the adaptive immune system is activated. New findings contribute to a better understanding of the pathophysiology of sepsis and lead to the development of new therapeutic strategies. The innate immune system, being responsible for the first response to infections, can trigger adaptive immune responses in case the initial response is ineffective. Both arms of the immune system interact with each other, mainly via cell-cell-interactions but also by soluble factors, such as cytokines and chemokines. Two sub-populations of helper T-cells direct both balanced activation and inhibition of the two arms of the immune systems using specific patterns of cytokine release. Results obtained in new animal models of sepsis, taking a progressive growth of bacteria into account, have implied that existing knowledge has to be reanalyzed. The idea of sepsis as a mere "over-reaction to inflammation" has to be abandoned. Various so-called pattern recognition receptors (e.g. toll-like receptors, TLRs, NOD proteins) are located intracellularly or in the plasma membrane of innate immune cells and recognize certain patterns expressed exclusively by extracellular pathogens. Upon receptor engagement, intracellular signaling pathways lead to cellular activation, followed by release of various cytokines and anti-microbial substances. During the course of sepsis a cytokine shift towards increasing immune suppression occurs. The innate immune system also contributes to the migration of leukocytes in inflammed tissue, involving chemokines and adhesion molecules. Leukocytes also secrete the tissue factor leading to formation of thrombin. The environment in sepsis can cause disseminated intravascular coagulation (DIC), but at the same time thrombin triggers the release of chemokines and adhesion molecules through endothelial cells, which represents a positive feedback mechanism for innate immune responses. New therapeutic strategies for sepsis try to establish a well-balanced immune response. Intervention is accomplished through inhibition of inflammatory cytokines, their receptors or through activation of immunostimulatory responses.

Animals↗

[Invasive techniques in emergency medicine. I. Practice-oriented training concept to ensure adequately qualified emergency physicians].

Based on written surveys conducted during the series of workshops entitled "Invasive emergency techniques (INTECH)" the aim of this study was to characterize defined qualifications of emergency physicians and to discuss by examples whether strictly practice-oriented workshops represent a suitable means of closing the apparent gaps in training. Our data show clearly that even experienced emergency physicians indicated that they lack training in carrying out preclinical invasive emergency procedures such as chest tube, cricothyrotomy and intraosseous access. Furthermore, they are only very seldom confronted with emergency situations in which these procedures could decidedly affect the survival of a patient and which, at the same time, put them under extremely high emotional pressure. Thus, the didactic concept of continuing education workshops that are strictly practice-oriented and that focus in particular on problem areas in emergency medicine, can contribute significantly to help close the gaps in training and ensure that emergency physicians are highly qualified.

Clinical Competence↗

Real-time ultrasonic observation of combined spinal-epidural anaesthesia.

BACKGROUND AND OBJECTIVE: The quality of combined spinal-epidural anaesthesia mainly depends on accurate identification of the epidural space. The real-time ultrasound control of the procedure for puncture was therefore evaluated. METHODS: Thirty parturients scheduled for Caesarean section were randomized to three equal groups. Ten control patients received conventional combined spinal-epidural anaesthesia. Ten of the remaining patients received ultrasonic scans by an offline scan technique, and 10 received online imaging of the lumbar region during epidural puncture. The epidural space was identified and needle advancement was surveyed through the interspinal and flaval ligaments. The number of attempts to advance the needle to achieve a successful puncture was measured and compared, as well as the number of vertebral interspaces punctured before successful entry into the epidural space. RESULTS: There was no difference between patient characteristics in the three groups. The visualization of the epidural structures and of the needle manipulations was very effective. In the ultrasound group, the reduction in the number of attempts at puncture was significant (P < 0.036). The number of interspaces necessary for puncture was reduced (P < 0.036) in the ultrasound online group compared with controls. The number of spinal needle manipulations was significantly reduced (P < 0.036). CONCLUSIONS: Real-time ultrasonic scanning of the lumbar spine is an easy procedure. It provides an accurate reading of the location of the needle tip and facilitates the performance of combined spinal-epidural anaesthesia.

Adult↗

Cost-effectiveness and high patient satisfaction in the elderly: sevoflurane versus propofol anaesthesia.

BACKGROUND AND OBJECTIVE: The use of propofol compared with isoflurane is associated with improved patient comfort and decreased costs. However, as the cost saving, the quicker recovery time and patient comfort may not be evident if sevoflurane is substituted for isoflurane; these two anaesthetic agents were analysed in elderly patients. METHODS: In a prospective randomized study, 96 patients undergoing elective ophthalmic surgery received either total intravenous anaesthesia with propofol (Group P), propofol for induction and sevoflurane for maintenance (Group P/S) or sevoflurane for inhalation induction and maintenance (Group S). Analyses focussed on haemodynamics, the quality of recovery, and the costs for the anaesthetic and the entire procedure. RESULTS: Bradycardia or hypotension, mainly registered in Groups P and P/S, did not influence patients' recovery. In Group S, postoperative nausea and vomiting occurred frequently, and 50% of patients complained of discomfort during induction. In Group P/S, the costs for anaesthetics and total costs were lower than those in Groups P and S. CONCLUSIONS: Propofol- and sevoflurane-based maintenance of anaesthesia were similar with regard to patient comfort and recovery in the elderly. Cost analysis revealed that it was less expensive to use propofol for induction and sevoflurane for maintenance than to use either propofol or sevoflurane as sole agents for anaesthesia.

Aged↗

Acupuncture compared to placebo-acupuncture for postoperative nausea and vomiting prophylaxis: a randomised placebo-controlled patient and observer blind trial.

This randomised, placebo-controlled, patient and observer blinded trial was conducted to determine whether acupuncture at the acupuncture point P6 is effective in preventing postoperative nausea and vomiting (PONV) compared to placebo acupuncture. Female patients (n = 220) scheduled for gynaecological or breast surgery were randomly assigned to two groups receiving either acupuncture (n = 109) or placebo acupuncture (n = 111). Each group was stratified for type of surgery and included two subgroups receiving intervention either before or after induction of anaesthesia. The incidence of PONV and/or antiemetic rescue medication within 24 h after surgery was the main outcome measure which showed no statistically significant difference between groups (43.7% acupuncture, 50.9% placebo, p = 0.27). The differences were more pronounced for patients having gynaecological surgery (48.9% acupuncture, 67.6% placebo, p = 0.07) than for those having breast surgery (38.7% acupuncture, 40.3% placebo, p = 0.86). The secondary outcome, vomiting, was significantly reduced by acupuncture from 39.6% to 24.8% (p = 0.03). Subgroup analysis showed no difference between applications of acupuncture before compared to after induction of anaesthesia.

Acupuncture Therapy↗

Cerebral and extracerebral release of protein S100B in cardiac surgical patients.

Although several clinical studies have shown that increased serum concentrations of protein S100B predict ischaemic brain damage after cardiac surgery, S100B may also be released from the heart or other injured tissue. We therefore investigated the correlation between serum S100B levels and those of the specific cardiac marker troponin I in order to assess the cerebral vs. extracerebral origin of S100B. In 64 cardiac surgical patients, serial blood samples were drawn for the measurement of S100B and troponin I before surgery and for seven days after surgery. Neurological function was assessed before with the National Institutes of Health Stroke Scale and the Folstein Mini Mental Test. The data show that a sustained increase in serum S100B levels is associated with neurological dysfunction, as witnessed by a positive correlation between S100B values and the results of the neuropsychological tests. In contrast, the early postoperative increased levels of protein S100B derive from cardiac tissue, as shown by the positive correlation between S100B and cardiac troponin I levels.

Adult↗

Continuous assessment of right ventricular ejection fraction: new pulmonary artery catheter versus transoesophageal echocardiography.

In 25 cardiac surgical patients, right ventricular ejection fraction was continuously measured with a new pulmonary artery catheter and transoesophageal echocardiography, scanning the 'fractional area change' in a standardised transatrial cross section area. Measurements were recorded at three predefined time points (pre-, intra-, and postoperatively). Both methods were compared using the Bland-Altman analysis. Comparing right ventricular ejection fraction values obtained from the pulmonary artery catheter with those assessed by transoesophageal echocardiography, bias was -3.7%, with a precision of 30.9%. Bias and precision significantly improved when the heart rate was less than 100 beats.min(-1), pulmonary artery pressures were low and cardiac performance adequate. In conclusion, the new continuous pulmonary artery catheter system appears to be a valid and useful bedside monitoring device in the haemodynamic management of critically ill patients.

Aged↗

Postoperative 12-lead ECG predicts peri-operative myocardial ischaemia associated with myocardial cell damage.

Peri-operative myocardial ischaemia is the single most important risk factor for an adverse cardiac outcome after non-cardiac surgery. The present study examines whether intermittent 12-lead ECG recordings can be used as an early warning tool to identify patients suffering from peri-operative myocardial ischaemia and subsequent myocardial cell damage. Fifty-five vascular surgery patients at risk for or with a history of coronary artery disease were monitored for peri-operative myocardial ischaemia using intermittent 12-lead ECG recordings taken pre-operatively and at 15 min, 20 h, 48 h, 72 h and 84 h postoperatively. The effectiveness of the 12-lead ECG was gauged by examining concordance with continuous 3-channel Holter monitoring and capturing peri-operative myocardial ischaemia by serial analyses of creatine kinase myocardial band isoenzyme and cardiac troponin T and I. The incidence of peri-operative myocardial ischaemia detected by 12-lead ECG was 44% and was identifiable in most patients (88%) 15 min after surgery. The incidence of peri-operative myocardial ischaemia detected by continuous monitoring was 53%, with the most severe episodes occurring intra-operatively and during emergence from anaesthesia. The concordance of the 12-lead method with continuous monitoring was 72%. The concordance of creatine kinase myocardial band isoenzyme activity with the 12-lead method was 71% and with Holter monitoring 57%. The concordance of mass concentration of creatine kinase myocardial band with 12-lead ECG recordings was 75%, and the corresponding value for Holter monitoring was 68%. The concordance of cardiac troponin T and I levels with the 12-lead method was 85% and 87%, respectively, and concordance with Holter monitoring was 72% and 66%, respectively. The postoperative 12-lead ECG identified peri-operative myocardial ischaemia associated with subsequent myocardial cell damage in most patients undergoing vascular surgery.

Aged↗