Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative,BCR-positive patients with chronic myeloid leukemia

Leukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR-ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph-positive CML and in almost all investigated CML with variant Ph or Ph-negative, BCR-positive cases. The few aberrant chromosomal localizations of BCR-ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR-ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph-negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley-Liss, Inc.     

Effect of an education and activation programme on functional limitations and patient-perceived recovery in acute and sub-acute shoulder complaints – a randomised clinical trial

Background  

The education and activation programme (EAP) aims at coping with psychosocial determinants to prevent the development of chronic shoulder complaints (SCs). The effect of the EAP on functional limitations and patient-perceived recovery after 6 and 26 weeks is evaluated in a randomised clinical trial.     

Assessment of vital exhaustion and identification of subjects at increased risk of myocardial infarction in general practice

Vital exhaustion, a state characterized by unusual fatigue, loss of energy, increased irritability, and feelings of demoralization, is one of the cardiovascular risk factors. The authors investigated whether vital exhaustion contributes to the identification of subjects at increased risk of myocardial infarction in general practice. In this prospective cohort study, vital exhaustion was assessed with the Maastricht Interview on Vital Exhaustion. Other cardiovascular risk factors established were age, gender, systolic and diastolic blood pressure, total cholesterol, body mass index, smoking habits, cardiovascular disease, and diabetes mellitus. A Cox regression analysis was used. The subjects were adults (41-66 years) in an average Dutch village population. Outcome measures were fatal and nonfatal myocardial infarction. At the univariate level, vital exhaustion doubled the risk of myocardial infarction. The effect of exhaustion was confounded by gender; women had higher exhaustion scores and a lower incidence of myocardial infarction. With control for gender, age, systolic blood pressure, total cholesterol, smoking habits, self-reported cardiovascular disease, and diabetes mellitus, vital exhaustion almost tripled the risk of myocardial infarction. Assessment of vital exhaustion contributes to the identification of subjects at increased risk of myocardial infarction in general practice.     

Understanding laboratory testing in diagnostic uncertainty: a qualitative study in general practice.

BACKGROUND: Better knowledge of the professional's motives for ordering laboratory tests in the case of diagnostic uncertainty may lead to interventions directed at reducing unnecessary testing. AIM: To gain insight into the general practitioner's (GP's) motives for ordering laboratory tests for patients presenting with unexplained complaints. DESIGN OF STUDY: Semi-structured interviews based on surgery observations. SETTING: Twenty-one general practices in rural and urban areas of The Netherlands. METHOD: Investigation of the GP's perception of determinants of test-ordering behaviour in the situation of diagnostic uncertainty. The interviews were structured by evaluating the consultations and test-ordering performance of that day. RESULTS: Dutch GPs vary considerably in their motives for ordering tests. Numerous motives emerged from the data. Some examples of important themes include: personal routines; tolerance of diagnostic uncertainty; time pressure; and tactical motives for test ordering. Complying with the perceived needs of the patient for reassurance through testing is seen as an easy, cost- and time-effective strategy. A clear hierarchy in the determinants was not found. CONCLUSION: The decision to request laboratory testing is the result of a complex interaction of considerations that are often conflicting. Designers of interventions meant to improve the ordering of tests should be aware of the numerous determinants, and take contextual variables into account.     

Prehospital Echocardiography During Resuscitation Impacts Treatment in a Physician-Staffed Helicopter Emergency Medical Service: an Observational Study

Background: Patients in cardiac arrest must receive algorithm-based management such as basic life support and advanced (cardiac) life support. International guidelines dictate diagnosing and treating any factor that may have caused the arrest or may be complicating the resuscitation. Ultrasound may be of potential value in this process and can be used in a prehospital setting. The objective is to evaluate the use of prehospital ultrasound during traumatic and non-traumatic CPR and determine its impact on prehospital treatment decisions in a Dutch helicopter emergency medical service (HEMS). Methods: We conducted an observational study in cardiac arrest patients, of any cause, in whom the Nijmegen HEMS performed CPR with concurrent echocardiography. The participating physicians had to adhere to Advanced Life Support protocols as per standard operating procedure. Simultaneous with the interruptions of chest compressions to allow for heart rhythm analysis, ultrasound-trained HEMS physicians performed echocardiography according to study protocol. The HEMS nurse and physician recorded patient data and data on impacted (supported or altered) patient treatment decisions. Results: From February 2014 through November 2016, we included 56 patients who underwent 102 ultrasound examinations. Sixty-two (61%) ultrasound examinations impacted 78 treatment decisions in 49 patients (88%). The impacted treatment was related to termination of CPR in 32 (57%), fluid management (14%), drugs selection and doses (14%), and choice of destination hospital (5%). Causes of cardiac arrest included trauma (48%), cardiac (21%), medical (14%), asphyxia (9%), and other (7%). Conclusion: Prehospital echocardiography has an impact on patient treatment and may be a useful tool to support decision-making during CPR in a Dutch HEMS.     

Equilibrium point control cannot be refuted by experimental reconstruction of equilibrium point trajectories

In the literature, it has been hotly debated whether the brain uses internal models or equilibrium point (EP) control to generate arm movements. EP control involves specification of EP trajectories, time series of arm configurations in which internal forces and external forces are in equilibrium; if the arm is not in a specified EP, it is driven toward this EP by muscle forces arising due to central drive, reflexes, and muscle mechanics. EP control has been refuted by researchers claiming that EP trajectories underlying movements of subjects were complex. These researchers used an approach that involves applying force perturbations during movements of subjects and fitting a mass-spring-damper model to the kinematic responses, and then reconstructing the EP trajectory using the estimated stiffness, damping, and measured kinematics. In this study, we examined the validity of this approach using an EP-controlled musculoskeletal model of the arm. We used the latter model to simulate unperturbed and perturbed maximally fast movements and optimized the parameter values of a mass-spring-damper model to make it reproduce as best as possible the kinematic responses. It was shown that estimated stiffness not only depended on the "true" stiffness of the musculoskeletal model but on all of its dynamical parameters. Furthermore it was shown that reconstructed EP trajectories were in agreement with those presented in the literature but did not resemble the simple EP trajectories that had been used to generate the movement of the model. It was concluded that the refutation of EP control on the basis of results obtained with mass-spring-damper models was unjust.     

The impact of endpoint measures in rheumatoid arthritis clinical trials.

In clinical trials on the effectiveness of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), it is common to apply a large number of endpoint measures. This practice has several disadvantages. To determine which endpoint measures are most valuable, reports of 32 clinical trials on six DMARDs were reviewed. The frequency with which each endpoint measure was used is described and discussed, as well as the frequency with which the values of each endpoint were significantly different in statistical comparisons within or between groups, thus showing ability to discriminate between drugs not equally effective. The results of this review are discussed and compared with other reports in the literature on the choice of endpoint measures in RA clinical trials. The authors conclude that it is still common practice to evaluate multiple outcome measures. The number of measures could be reduced by using only those that are generally considered important, are sensitive to change, and are able to differentiate between drugs in clinical trials. A joint count, assessment of pain, a questionnaire on functional status, and measurement of erythrocyte sedimentation rate are sufficient.