A study of the genetics of dieldrin-resistance in the housefly (Musca domestica L.)

Reciprocal mass crosses and back-crosses were performed between two homogeneous strains of the housefly (Musca domestica L.), representing the extremes in susceptibility and resistance to dieldrin. The heterozygotes were found to be intermediate between susceptible and resistant parents, and showed no evidence of sex linkage or cytoplasmic effects. The F₂ generation segregated in an approximate ratio of 1:2:1 into susceptible, heterozygote and resistant phenotypes, while the back-cross to the susceptible parent yielded 49.8:50.2 susceptible: resistant males, and 48.8:51.2 susceptible: resistant females. Elimination of susceptible forms in the back-cross progeny by use of a discriminating dosage and interbreeding the survivors produced offspring segregating into 26% susceptible, 50.1% heterozygote and 23.9% resistant, in excellent statistical agreement with a ratio of 1:2:1 expected in simple Mendelian inheritance. It is concluded that resistance to dieldrin in the housefly strain studied is due primarily to a major single pair of alleles or to a number of closely linked alleles so that they are inherited as a single unit.     

Reciprocal peer teaching: students teaching students in the gross anatomy laboratory

Three common instructional strategies used to teach gross anatomy are lecture, discovery or inquiry-based learning, and cooperative learning. One form of cooperative learning, called reciprocal peer teaching (RPT), illustrates circumstances where students alternate roles as teacher and student. By assuming the responsibility of teaching their peers, students not only improve their understanding of course content, but also develop communication skills, teamwork, leadership, confidence and respect for peers that are vital to developing professionalism early in their medical careers. Traditionally in our Anatomy department, students dissect the entire body using a standard dissection manual. More non-traditionally, however, we have increased cooperative learning in the dissection laboratory by involving students in a series of supplementary RPT activities. During these exercises, 10% of the class practiced their demonstration with course instructors until the students felt prepared to demonstrate the exercise to their classmates. We designed one peer demonstration emphasizing three to six teaching objectives for most of the 40 dissection units. This resulted in a compendium of peer demonstrations for implementation throughout the course. The multitude of diverse exercises permitted each student many opportunities to teach their peers. A debriefing questionnaire was administered at the end of the course demonstrating that 100% of students agreed the RPT experience increased their understanding of the topics they taught and 97% agreed it increased their retention of information they taught to their peers. In addition, 92% agreed that RPT improved their communication skills, which can be applied beyond anatomy to their careers as future physicians.     

Using and teaching evidence-based medicine: the Duke University child and adolescent psychiatry model

Evidence-based medicine (EBM) is defined as a set of processes that facilitate the conscientious, explicit, and judicious integration of individual clinical expertise with the best available external clinical evidence from systematic research in making decisions about the care of individual patients. EBM focuses not only on grading the strength of the evidence but also on the processes and tools that are necessary for clinicians to continually upgrade their knowledge and skills for those problems encountered in daily practice. This article, authored by members of the Duke Pediatric Psychiatry EBM Seminar Team, (1) describes EBM as applied to the training of child and adolescent psychiatrists in the Division of Child and Adolescent Psychiatry, Department of Psychiatry at Duke University Medical Center; (2) presents a simplified discussion of EBM as a technology for training and patient care; (3) discusses the basic principles and procedures for teaching EBM in the setting of a multidisciplinary training program; and (4) briefly mentions two training and research initiatives that are furthered by incorporating EBM.     

The case for practical clinical trials in psychiatry

OBJECTIVE: Clinical trials in psychiatry frequently fail to maximize clinical utility for practicing clinicians, or, stated differently, available evidence is not perceived by clinicians (and other decision makers) as sufficiently relevant to clinical practice, thereby diluting its impact. To attain maximum clinical relevance and acceptability, researchers must conduct clinical trials designed to meet the needs of clinicians and others who are making decisions about patients' care. The authors present the case for psychiatry's adoption of the practical clinical trials model, which is widely used in research in other areas of medicine. METHOD: The authors outline the characteristics and scope of practical clinical trials, give examples of practical clinical trials, and discuss the challenges of using the practical clinical trials model in psychiatry, including issues of funding. RESULTS: Practical clinical trials, which are intended to provide generalizable answers to important clinical questions without bias, are characterized by eight key features: a straightforward clinically relevant question, a representative sample of patients and practice settings, sufficient power to identify modest clinically relevant effects, randomization to protect against bias, clinical uncertainty regarding the outcome of treatment at the patient level, assessment and treatment protocols that enact best clinical practices, simple and clinically relevant outcomes, and limited subject and investigator burden. CONCLUSIONS: To implement the practical clinical trials model in psychiatry will require stable funding for network construction and maintenance plus methodological innovation in governance and trial selection, assessment, treatment, data management, site management, and data analytic procedures.     

Functional impairment in elderly patients hospitalised in an Internal Medicine unit

To determine the functional status in elderly patients after a hospitalisation in an Internal Medicine unit. We prospectively studied patients aged 80 or above hospitalised in the Hospital Provincial de Ciudad Real in an Internal Medicine unit, between February and July, 2003. The functional status was determined by Barthel Index. We examined 206 patients (77.4%). They showed a previous Barthel Index of 70.9; one of 48.9 in the hospitalisation stage and one of 58.6 when discharged (p<0.001). We noticed a Barthel Index when discharged which was lower than the previous Barthel one in 73.8% patients. Hospitalisation implies a great functional impairment in the functional status elderly patients. It would be convenient, therefore, to identify the risk factors to be able to set some guidelines for a preventive model.     

Differential expression of SAP and EAT-2-binding leukocyte cell-surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4)

The CD150 (SLAM) family consists of nine leukocyte cell-surface proteins involved in lymphocyte activation that belong to the immunoglobulin (Ig) superfamily. Six members of this family--CD84, CD150 (SLAM), CD229 (Ly9), CD244 (2B4), NTB-A, and CS1--associate with adapter proteins--SLAM-associated protein (SAP) and EAT-2. SAP is a short intracellular molecule that is mutated in humans with X-linked lymphoproliferative disease. Flow cytometric analysis of the expression of CD84, CD150, CD229, and CD244 cell-surface receptors on several leukocyte and lymphocyte subsets was performed. CD84 and CD150 were present on thymocytes, mature T cells and antigen-presenting cells. The expression of CD84 and CD150 was high on memory T cells. CD150 expression was strongly up-regulated after cell activation. In contrast to CD84, CD150 was absent on resting monocytes and immature dendritic cells (DCs). CD229 presented a pattern of expression restricted to lymphocytes. CD244 was preferentially expressed on natural killer cells, CD8(+) effector cells, resting monocytes, basophils, and eosinophils. We describe a broader distribution of CD84, CD150, CD229, and CD244 than previously reported and show that they are differentially expressed on hematopoietic cells. The heterogeneous expression of these receptors indicates that these molecules may play non-redundant functions in the regulation of both innate and adaptive immune responses.     

Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response

A biphasic cardiovascular response to bolus i.v. injection of human urotensin II (hUII, 3 nmol kg(-1)) in conscious, male, Sprague-Dawley (SD) rats was identified and underlying mechanisms were explored. Initially (0-5 min) there was tachycardia, hypotension and mesenteric and hindquarters vasodilatation; later (30-120 min), tachycardia, hindquarters vasodilatation and a modest rise in blood pressure occurred. Pretreatment with indomethacin or N(G) nitro-l-arginine methylester (l-NAME) reduced the mesenteric vasodilator response to hUII, and abolished the late tachycardia and hindquarters vasodilatation. Indomethacin also abolished the hypotension and early hindquarters vasodilatation, and substantially reduced the initial tachycardia. Indomethacin and l-NAME together prevented all haemodynamic responses to hUII. Inhibition of inducible NOS had no effect on responses to hUII, whereas inhibition of neuronal NOS reduced the delayed tachycardic response to hUII but did not significantly affect the vasodilatation. Only the initial tachycardic response to hUII was antagonised by propranolol. In spontaneously hypertensive rats (SHR), the initial haemodynamic responses to hUII were qualitatively similar to those in SD rats, although there was also a modest renal vasodilatation. The secondary response comprised a smaller tachycardia and a small rise in blood pressure, with no significant hindquarters vasodilatation. Haemodynamic responses to hUII were not enhanced by endothelin and angiotensin receptor antagonism in either SD rats or in SHRs. One interpretation of these results is that the primary response to bolus injection of hUII is prostanoid- or prostanoid- and NO-mediated (mesenteric vasodilatation) and that this triggers secondary events, which are dependent on eNOS (hindquarters vasodilatation) and neuronal NOS (tachycardia).     

Inhalation toxicity of brevetoxin 3 in rats exposed for 5 days

Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the compounds become aerosolized by wind and surf. This study assesses possible adverse health effects associated with short-term inhalation exposure to brevetoxin 3. Male F344/Crl/Br rats were exposed to 500 microg brevetoxin 3/m3 by nose-only inhalation for 0.5 or 2 h/d for 5 consecutive days. Control rats were sham exposed for 2 h to vehicle. Calculated deposited brevetoxin doses were 8.3 and 33 microg/kg/d for the low- and high-dose groups, respectively. At the termination of exposures, only body weights of the high-dose group (Group B) were significantly below control values. By immunohistochemistry (IHC), small numbers of splenic and peribronchiolar lymphoid tissue macrophages stained positive for brevetoxin, while nasal mucosa, liver, and brain were IHC negative for brevetoxin. No gross or microscopic lesions were observed in any tissue examined. There was no biochemical evidence of cytotoxicity or inflammation in bronchoalveolar lavage fluid. Alveolar macrophages showed some evidence of activation following brevetoxin exposure. Humoral-mediated immunity was suppressed in brevetoxin-exposed rats as indicated by a >70% reduction in splenic plaque-forming cells in brevetoxin-exposed animals compared to controls. Results suggest that the immune system may be a target of toxicity following brevetoxin inhalation. Future studies will focus on identification of a no-effect level and mechanisms underlying brevetoxin-induced immune suppression.