Presynaptic alpha-block and inhibition of noradrenaline and 5-hydroxytryptamine reuptake by a series of compounds related to mianserin

A structure-activity relationship study was undertaken for a variety of structural analogues of the tetracyclic antidepressant mianserin. Presynaptic alpha-blocking activity in vitro was evaluated measuring the potentiation of depolarization-induced noradrenaline (NA) release from rat cerebral cortex slices. Inhibition of NA and 5-hydroxytryptamine reuptake was measured in rat hypothalamic or striatal synaptosomes, respectively. Presynaptic alpha-blockade was only found in molecules with an overall bent shape. Flat rigid molecules or flexible ones were not active. Six-membered, chair-formed D-rings (containing the -NCH3 moiety) appeared better than 5- or 7-membered ones. Heteroatom substitution, but not hydroxylation or methylation, of the bridge between the two aromatic rings left presynaptic alpha-blockade unaffected. N-Demethylation and aromatic methyl- or chlorine-substitution reduced presynaptic alpha-blockade. In pyridine ring-substituted analogues the localization of the heteroatom appeared to be crucial. 5-Hydroxytryptamine reuptake inhibitory activity was only found in desmethylmianserin. NA uptake inhibition was found in many mianserin analogues, especially those with an exocyclic-N(CH3)2 moiety. Structure activity relationships for NA reuptake inhibition differed from those for presynaptic alpha-blockade and were generally less stringent. For both properties simple additivity relationships appeared to be absent.     

Analysis of verbal communication during teaching in the operating room and the potentials for surgical training

BACKGROUND: Verbal communication in the operating room during surgical procedures affects team performance, reflects individual skills, and is related to the complexity of the operation process. During the procedural training of surgeons (residents), feedback and guidance is given through verbal communication. A classification method based on structural analysis of the contents was developed to analyze verbal communication. This study aimed to evaluate whether a classification method for the contents of verbal communication in the operating room could provide insight into the teaching processes. METHODS: Eight laparoscopic cholecystectomies were videotaped. Two entire cholecystectomies and the dissection phase of six additional procedures were analyzed by categorization of the communication in terms of type (4 categories: commanding, explaining, questioning, and miscellaneous) and content (9 categories: operation method, location, direction, instrument handling, visualization, anatomy and pathology, general, private, undefinable). The operation was divided into six phases: start, dissection, clipping, separating, control, closing. RESULTS: Classification of the communication during two entire procedures showed that each phase of the operation was dominated by different kinds of communication. A high percentage of explaining anatomy and pathology was found throughout the whole procedure except for the control and closing phases. In the dissection phases, 60% of verbal communication concerned explaining. These explaining communication events were divided as follows: 27% operation method, 19% anatomy and pathology, 25% location (positioning of the instrument-tissue interaction), 15% direction (direction of tissue manipulation), 11% instrument handling, and 3% other nonclassified instructions. CONCLUSION: The proposed classification method is feasible for analyzing verbal communication during surgical procedures. Communication content objectively reflects the interaction between surgeon and resident. This information can potentially be used to specify training needs, and may contribute to the evaluation of different training methods.     

Use of femur length/abdominal circumference ratio in detecting the macrosomic fetus

The femur length/abdominal circumference ratio, expressed as FL/AC X 100, was determined in 156 fetuses and evaluated as a predictor of fetal macrosomia within one week prior to delivery. The normal range (mean +/- 2 SD) in the 105 normal-weight fetuses was 22.0 +/- 2, while the normal range in the 51 macrosomic fetuses was 20.5 +/- 2; these differences were highly significant (P = less than .0001). The predictive power of a positive ratio was 68%, with a sensitivity of 63%. This ratio was particularly useful in the subset (n = 9) of macrosomic fetuses whose mothers were diabetic, correctly identifying 89% of this group. Because it is age independent, this ratio should prove most helpful in identifying fetuses at risk for macrosomia in patients whose dates are not known, since it may become abnormal before the fetal weight falls above the 90th percentile at term (3,900 g). In patients whose dates are known, early fetal macrosomia is best predicted by evaluating the abdominal circumference against normal standards for age.     

Comparison of Micronutrient Intervention Strategies in Ghana and Benin to Cover Micronutrient Needs: Simulation of Bene-Fits and Risks in Women of Reproductive Age

Overlapping micronutrient interventions might increase the risk of excessive micronutrient intake, with potentially adverse health effects. To evaluate how strategies currently implemented in Benin and Ghana contribute to micronutrient intake in women of reproductive age (WRA), and to assess the risk for excess intakes, scenarios of basic rural and urban diets were built, and different on-going interventions were added. We estimated micronutrient intakes for all different scenarios. Four types of intervention were included in the scenarios: fortification, biofortification, supplementation and use of locally available nutrient-rich foods. Basic diets contributed poorly to daily micronutrient intake in WRA. Fortification of oil and salt were essential to reach daily requirements for vitamin A and iodine, while fortified flour contributed less. Biofortified products could make an important contribution to the coverage of vitamin A needs, while they were not sufficient to cover the needs of WRA. Iron and folic acid supplementation was a major contributor in the intake of iron and folate, but only in pregnant and lactating women. Risk of excess were found for three micronutrients (vitamin A, folic acid and niacin) in specific contexts, with excess only coming from voluntary fortified food, supplementation and the simultaneous overlap of several interventions. Better regulation and control of fortification and targeting of supplementation could avoid excess intakes.     

Strategies to prevent iron deficiency and improve reproductive health

Anemia and iron deficiency affect billions of people worldwide, especially women of reproductive age, pregnant women, and young children. Many countries have iron and folic acid supplementation programs for pregnant women. However, the impact of these programs is uncertain. Multiple-micronutrient supplementation during pregnancy has been advocated; however, it is unclear whether this has additional advantages. Overall, programs have shown only modest impact on increasing birth weight. This review discusses the present state of knowledge on interventions to improve iron status during pregnancy and reproductive health, and investigates other possibilities such as supplementation prior to conception to improve maternal and child health.     

Is it time to drop the ‘knowledge translation’ metaphor? A critical literature review

The literature on 'knowledge translation' presents challenges for the reviewer because different terms have been used to describe the generation, sharing and application of knowledge and different research approaches embrace different philosophical positions on what knowledge is. We present a narrative review of this literature which deliberately sought to highlight rather than resolve tensions between these different framings. Our findings suggest that while 'translation' is a widely used metaphor in medicine, it constrains how we conceptualise and study the link between knowledge and practice. The 'translation' metaphor has, arguably, led to particular difficulties in the fields of 'evidence-based management' and 'evidence-based policymaking' - where it seems that knowledge obstinately refuses to be driven unproblematically into practice. Many non-medical disciplines such as philosophy, sociology and organization science conceptualise knowledge very differently, as being (for example) 'created', 'constructed', 'embodied', 'performed' and 'collectively negotiated' - and also as being value-laden and tending to serve the vested interests of dominant élites. We propose that applying this wider range of metaphors and models would allow us to research the link between knowledge and practice in more creative and critical ways. We conclude that research should move beyond a narrow focus on the 'know-do gap' to cover a richer agenda, including: (a) the situation-specific practical wisdom (phronesis) that underpins clinical judgement; (b) the tacit knowledge that is built and shared among practitioners ('mindlines'); (c) the complex links between power and knowledge; and (d) approaches to facilitating macro-level knowledge partnerships between researchers, practitioners, policymakers and commercial interests.     

Pediatricians' awareness of and attitudes about four clinical practice guidelines

BACKGROUND: The increasing complexity of medical care and a desire to increase quality and control costs have led to growing use of clinical practice guidelines (CPGs). It is unclear how helpful these guidelines are to the practitioners expected to use them. We surveyed pediatricians about their knowledge and impressions of four well-publicized CPGs: the American Academy of Pediatrics' "Practice Parameter for Hyperbilirubinemia in Newborns" (hyperbilirubinemia), "A Guideline for the Management of Febrile Infants" (fever), the Agency for Health Care Policy and Research's "Guideline for Otitis Media With Effusion" (otitis), and the US Preventive Services Task Force Guide to Clinical Preventive Services (preventive care). OBJECTIVES: 1) What percentage of practicing pediatricians are aware of these guidelines? 2) How helpful do they find them? 3) What are practitioners' perceived limitations of these guidelines? 4) Have these guidelines affected provider behavior? 5) Are there features of a provider's training or practice that are associated with changing practice as a result of guidelines? DESIGN: A national survey of 600 pediatricians selected at random from the American Medical Association master file. RESULTS: A total of 300 of 555 eligible participants (54%) returned surveys. Of the respondents, 66% were aware of the hyperbilirubinemia guideline, 64% of the fever guideline, 50% of the otitis guideline, but only 16% knew of the preventive care guidelines. Mean helpfulness scores (1 to 10 scale, where 1 = "not at all helpful" and 10 = "extremely helpful") ranged from 3.67 to 6.67 for the different guidelines. In terms of limitations, 15% to 33% of respondents reported that CPGs were "too cookbook," 6% to 19% reported that they were "too time-consuming," and 4% to 16% reported that they were "too cumbersome." Additional reported limitations were believing that a guideline left no room for personal experience and judgment, concern of increased liability risk, and poor parental acceptance of CPG recommendations. The proportions reporting change in management as a result of a CPG were 28% for the hyperbilirubinemia guideline, 36% for the fever guideline, 19% for the preventive care guidelines, and 28% for the otitis guideline. Mean helpfulness scores reported by nonuniversity-affiliated physicians were significantly higher than those reported by university-affiliated physicians. In a regression model of respondents aware of a particular guideline, more recent graduation from medical school and increased helpfulness scores were associated with guideline-related behavior change. CONCLUSION: In their present form, CPGs are not perceived as very helpful by most practitioners. More recent medical school graduates and nonuniversity-affiliated physicians are more likely to find them helpful and more likely to change their behavior because of them.