Interactive Decision Support for Risk Management: a Qualitative Evaluation in Cancer Genetic Counselling Sessions

Genetic counselling for inherited susceptibility to cancer involves communication of a significant amount of information about possible consequences of different interventions. This study explores counsellors' attitudes to computer software designed to aid this process. Eight genetic counsellors used the software with actors playing patients. Clinicians' rating of expected patient satisfaction, content, accuracy, timeliness, format, overall value, ease of use, effect on the patient–provider relationship and effect on clinician's performance were evaluated via qualitative and quantitative analysis of interviews, training tasks and questionnaires. Most counsellors found the software effective. Concerns related to possible impact on consultation dynamics and content. Participants suggested countering these through appropriate new counselling skills and selective use of the computer. The REACT software could provide effective support for genetic risk management counselling.     

Analgesia induced by electroconvulsive shock: brain enkephalins may mediate tolerance but not the induction of analgesia

Electroconvulsive shock (ECS) administered to rats produces potent analgesia. This analgesic effect displays opiate characteristics with tolerance to ECS analgesia seen with repeated induction and cross tolerance observed following the chronic administration of analgesic dose of morphine. Furthermore, tolerance development after repeated ECS application could be blocked by daily pretreatment with the long acting opiate antagonist naltrexone (5 mg/kg). In contrast to these opiate characteristics of ECS analgesia, naltroxone administration (0.5, 5 and 10 mg/kg) failed to attenuate the acute analgesic effect of ECS.

Measurement of brain enkephalin levels revealed an increase in enkephalin contents after 10 daily ECS applications, an effect which was not affected by naltrexone pretreatment. Acute administration of ECS did not affect brain enkephalin levels either immediately or 24 h after ECS administration. Significant increases in brain enkephalin following chronic ECS were observed in the hypothalamus and striatum but not in the mesencephalon or hindbrain. A gradual return of enkephalin levels to baseline values was seen with days when ECS was no longer administered. Parallel behavioral studies showed that ECS analgesia also showed a gradual recovery from tolerance after discontinuation of chronic ECS.

Based on these and previous studies we propose that different systems may mediated the acute analgesic effect of ECS on the one hand, and the tolerance to such an effect observed after repeated administration on the other. We further suggest that the acute action of ECS may be mediated by substances with only partial opiate characteristics, while the long term effects observed may be due to the increase in brain enkephalin contents after chronic ECS application.     

The effect of the distance between post and residual gutta-percha on the clinical outcome of endodontic treatment

To determine whether the distance between the post and the residual gutta-percha influences the clinical outcome of endodontic treatment, 94 endodontically treated teeth following post and core restoration were evaluated radiographically. The teeth were divided into three groups: (I) no gap between the gutta-percha and the post; (II) a gap of >0 to 2 mm; (III) a gap of >2 mm. Treatment outcome was evaluated in follow-up radiographs, taken 1 yr after treatment and up to 5 yr posttreatment. In group I, 83.3% of the teeth were evaluated normal, 53.6% of group II, and only 29.4% of group III. A gap between the gutta-percha and the post was related to an increased rate of emerged disease in endodontically treated teeth restored with a post and core.     

'The multiple-sit-to-stand' field test for older adults: what does it measure?

BACKGROUND: The need to predict decline in functional status in a large number of older adults has brought researchers and clinicians to develop easy-to-administer field tests. One of them is the 'multiple-sit-to-stand' (MSTS), which claims to measure leg strength. OBJECTIVE: To assess the extent to which the MSTS is a leg strength, leg endurance or general endurance test. METHODS: 49 independently functioning women (72.2 +/- 6.4 years) were assessed on the MSTS, on a submaximal stress test, and on strength and endurance of knee extensors measured by isokinetics. The knee extensors were selected, more than in other muscle groups responsible for movement of the lower extremity, as the largest range of motion, and the largest torques required while performing activities of daily living (ADL) is found in this group. RESULTS: The correlation of the MSTS with the stress test was moderate and significant but very low and nonsignificant with the isokinetic measurements. CONCLUSIONS: The MTST is not able to predict strength of knee extensors, the leading group of leg muscles in ADL. If at all, it predicts general endurance rather than any measure--muscle strength or muscle endurance--of lower extremities. Longitudinal studies assessing the potential of the MSTS to predict deterioration in ADL in older adults are recommended, as well as studies assessing other factors related to both MSTS and ADL, such as muscle-nerve coordination affecting multiple joint activities.     

Autoimmune-induced glutamatergic receptor dysfunctions: Conceptual and psychiatric practice implications

Glutamatergic neurotransmission is mediated via complex receptorial systems including N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) and metabotropic receptor subtypes and plays a critical role in the modulation of synaptic plasticity, mood, cognitive processes and motor behavior. Glutamatergic function deficits are hypothesized to contribute to the pathogenesis of neuropsychiatric disorders, including schizophrenia, mood and movement disorders. Accumulating data are rapidly leading to the characterization of specific types of autoimmune encephalitis in which the receptors and proteins critically involved in glutamatergic neurotransmission, e.g., NMDA, AMPA receptors, are antigen targets. Characteristic of these syndromes, antibodies alter the structure and/or function of the corresponding neuronal antigen resulting in clinical pictures that resemble pharmacological disease models. Presently the best characterized autoimmune glutamatergic disorder is anti-NMDA receptor encephalitis. This disorder manifests with intertwined psychiatric and neurological features, defines a new syndrome, reclassifies poorly defined clinical states and extends previous hypotheses, such as hypo-NMDA receptor function in schizophrenia. The characterization of autoimmune-induced glutamatergic receptor dysfunctions (AGRD) is likely to have a substantial conceptual impact upon our understanding of neuropsychiatric disorders including schizophrenia, affective and movement dysfunctions. Further definition of AGRD will provide additional guidelines for psychiatric diagnoses, identification of homogeneous patient subtypes within broad phenomenological classifications and will contribute to the development of personalized treatments. The body of knowledge already accumulated on anti-NMDA receptor encephalitis highlights the need for wide dissemination of these concepts among psychiatrists, and in suspected cases, for early recognition, prompt clinical and laboratory investigation and efficient interface between mental health and medical teams.     

Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44

Submicroscopic deletions involving chromosome 1q43-q44 result in cognitive impairment, microcephaly, growth restriction, dysmorphic features, and variable involvement of other organ systems. A consistently observed feature in patients with this deletion are the corpus callosal abnormalities (CCAs), ranging from thinning and hypoplasia to complete agenesis. Previous studies attempting to delineate the critical region for CCAs have yielded inconsistent results. We conducted a detailed clinical and molecular characterization of seven patients with deletions of chromosome 1q43-q44. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. Four patients had CCAs, and shared the smallest region of overlap that contains only three protein coding genes, CEP170, SDCCAG8, and ZNF238. One patient with a small deletion involving SDCCAG8 and AKT3, and another patient with an intragenic deletion of AKT3 did not have any CCA, implying that the loss of these two genes is unlikely to be the cause of CCA. CEP170 is expressed extensively in the brain, and encodes for a protein that is a component of the centrosomal complex. ZNF238 is involved in control of neuronal progenitor cells and survival of cortical neurons. Our results rule out the involvement of AKT3, and implicate CEP170 and/or ZNF238 as novel genes causative for CCA in patients with a terminal 1q deletion.     

Large,but not Small Sustained Tensile Strains Stimulate Adipogenesis in Culture

Understanding the mechanoresponsiveness of adipocytes and the characteristics of the mechanical stimuli that regulate adipogenesis is critically important in establishing knowledge in regard to the long-term effects of a sedentary lifestyle (or immobility in extreme medical conditions) as well as concerning obesity and related diseases. In this study we subjected 3T3-L1 preadipocytes cultured on elastic substrata to different levels of static equiaxial tensile strains within the physiological range, up to substrate tensile strain (STS) of 12%, while inducing differentiation in the cultures. Based on prior work which revealed that adipogenesis is accelerated in cultures subjected to STS of 12% by activating the mitogen-activated protein kinase kinase signaling pathway, we were specifically interested in identifying the STS levels which trigger this process. We hence monitored the production and accumulation of lipid droplets (LDs) using a non-destructive, image-processing-based method that we have previously developed, for a period of 4 weeks. The experimental data demonstrated accelerated adipogenesis in the cultures subjected to STS levels of 6%, 9%, and 12% with respect to cultures subjected to STS of 3% and (non-stretched) control cultures. This accelerated adipogenic response to the large sustained STS manifested in significantly larger numbers and greater sizes of LDs in the cultures that were stretched to large STS levels (p < 0.05), starting at approximately day 14 following induction of differentiation. Hence, indeed, there appears to be a certain tensile strain threshold, or domain—which is found within the physiological range—above which the responsiveness of adipocytes to sustained static stretching increases and is manifested in accelerated adipogenesis.     

Microcephaly-thin corpus callosum syndrome maps to 8q23.2-q24.12

Postnatal microcephaly is defined as normal head circumference at birth, which progressively declines to more than 2 standard deviations below the average for the patient's age and sex. We describe four patients from three consanguineous families of Arab Bedouin origin who presented with autosomal recessive inheritance of progressive microcephaly, spasticity, thin corpus callosum, pyramidal signs, and intellectual disability. Homozygosity mapping (Human Mapping NspI 250K arrays, Affymetrix, Santa Clara, CA) placed the disease locus at 8q23.2-q24.12. The candidate region includes 22 known or predicted genes, including RAD21, which is related to the cohesion complex EIF3H, which is involved in translation initiation, and TAF2, which may be involved in intellectual disability. Identification of the causative gene in our reported family will shed light on the pathogenesis of this severe condition.     

Family physicians leaving their clinic--the Balint group as an opportunity to say good-bye

The cornerstone of family medicine is the belief in both the continuity and availability of care. These beliefs are challenged when a doctor leaves his or her clinic because of personal reasons. In the example described in this article, the involvement of colleagues in a Balint group led a doctor to a flash insight into her conflicting feelings related to leaving her clinic. The group process helped her to prepare and deal with her own feelings and needs, as well as those of her patients and staff. Balint groups are a secure place to explore and gain insight into the emotional aspects of attachment and separation of physicians from their patients.