Effects of perceived patient demand on prescribing anti-infective drugs

BACKGROUND: Although patient demand is frequently cited by physicians as a reason for inappropriate prescribing, the phenomenon has not been adequately studied. The objectives of this study were to determine the prevalence of perceived patient demand in physician-patient encounters; to identify characteristics of the patient, physician and prescribing situation that are associated with perceived demand; and to determine the influence of perceived demand on physicians'' prescribing behaviour. METHODS: An observational study using 2 survey approaches was conducted in February and March 1996. Over a 2-day period 20 family physicians in the Toronto area completed a brief questionnaire for each patient encounter related to suspected infectious disease. Physicians were later asked in an interview to select and describe 1 or 2 incidents from these encounters during which perceived patient demand influenced their prescribing (critical incident technique). RESULTS: Perceived patient demand was reported in 124 (48%) of the 260 physician-patient encounters; however, in almost 80% of these encounters physicians did not think that the demand had much influence on their decision to prescribe an anti-infective. When clinical need was uncertain, 28 (82%) of 34 patients seeking an anti-infective were prescribed one, and physicians reported that they were influenced either "moderately" or "quite a bit" by perceived patient demand in over 50% of these cases. Of the 35 critical prescribing incidents identified during the interviews, anti-infectives were prescribed in 17 (49%); the reasons for prescribing in these situations were categorized. INTERPRETATION: This study provides preliminary data on the prevalence and influence of perceived patient demand in prescribing anti-infectives. Patient demand had more influence on prescribing when physicians were uncertain of the need for an anti-infective.     

Effects of alcohols on lipid bilayers with and without cholesterol: the dipalmitoylphosphatidylcholine system

Differential scanning calorimetry is a useful method to study the thermotropic phase transitions of a phospholipid bilayer. In the present study DSC is used to determine the effects of methanol and ethanol on DPPC and DPPC/2 mol% cholesterol bilayers. The biphasic effect of the main transition and the presence of an extra peak on the DSC cooling scans were observed above certain alcohol concentrations. In the presence of 2% cholesterol, the concentration at which the biphasic effect occurs is increased by both short-chain alcohols. 1,6-Diphenyl-1,3,5-hexatriene (DPH) is used as a fluorescent probe to directly determine the onset of interdigitation in these systems as reflected by a drop in the DPH fluorescence intensity.     

Cloning,sequencing, and characterization of the hexahydro-1,3,5-Trinitro-1,3,5-triazine degradation gene cluster from Rhodococcus rhodochrous

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a high explosive which presents an environmental hazard as a major land and groundwater contaminant. Rhodococcus rhodochrous strain 11Y was isolated from explosive contaminated land and is capable of degrading RDX when provided as the sole source of nitrogen for growth. Products of RDX degradation in resting-cell incubations were analyzed and found to include nitrite, formaldehyde, and formate. No ammonium was excreted into the medium, and no dead-end metabolites were observed. The gene responsible for the degradation of RDX in strain 11Y is a constitutively expressed cytochrome P450-like gene, xplA, which is found in a gene cluster with an adrenodoxin reductase homologue, xplB. The cytochrome P450 also has a flavodoxin domain at the N terminus. This study is the first to present a gene which has been identified as being responsible for RDX biodegradation. The mechanism of action of XplA on RDX is thought to involve initial denitration followed by spontaneous ring cleavage and mineralization.     

Myonuclear domain size varies along the lengths of maturing skeletal muscle fibers

In a skeletal muscle fiber, each myonucleus is responsible for gene expression in its surrounding cytoplasm. The region of cytoplasm associated with an individual myonucleus is termed myonuclear domain. However, little is known about domain size variation within individual muscle fibers. This study tests the hypothesis that myonuclear domains expressing neonatal myosin within end regions of maturing fibers will be smaller than domains elsewhere in the fibers. The model used is chicken pectoralis, where we have previously shown that during development repression of neonatal myosin radiates from the central region towards the fiber ends. Samples excised from birds aged nine through to 115 days after hatching were sectioned transversely. Using computer image analysis and immunocytochemistry, fiber profiles were classified as neonatal, transforming or adult. Each profile was also located in an adjacent dystrophin-labelled section, where myonuclei were visualized using haematoxylin and bisbenzamide. Variation in myonuclear length with age was not found to be significant (p = 0.925). Myonuclei were counted, and formulae used to calculate mean myonuclear domain size for each profile type. Myonuclear number/mm fiber was calculated to be adult (mean = 108.57 myonuclei/mm), transforming (65.82) and neonatal (25.23). Transforming profiles had significantly (p=0.027) more myonuclei/mm than neonatal, as did adult (p=0.005). Volume of cytoplasm/myonucleus was adult (mean = 16,132 microm3/myonucleus), transforming (12,899) and neonatal (8,130). Transforming and adult profiles had significantly (p<0.001) larger myonuclear domains than did neonatal profiles. Transforming and adult profiles did not differ in either myonuclei/mm (p=0.302) or volume of cytoplasm/myonucleus (p=0.413). This study demonstrates smaller domains at the terminal tips of maturing muscle fibers.     

Transfer of GRP94(Gp96)-associated peptides onto endosomal MHC class I molecules

GRP94 (gp96)-associated peptides can elicit cellular immune responses, an activity thought to reflect the presence of a cell surface receptor (CD91) on antigen-presenting cells that mediates GRP94 internalization and trafficking to an amenable site for peptide transfer to major histocompatibility complex class I molecules. We report that GRP94 internalized by receptor-mediated endocytosis is trafficked to a Rab5a, CD1 and transferrin-negative, Fc receptor and major histocompatibility complex class I-positive endocytic compartment. Receptor-internalized GRP94 did not access the endoplasmic reticulum of antigen-presenting cells. To identify the site of re-presentation of GRP94-associated peptides, kinetic analyses were performed utilizing GRP94-OVA (SIINFEKL) peptide complexes, with peptide re-presentation assayed with the K^b-SIINFEKL-specific MAb, 25-D1.16. Analyses of the kinetics of re-presentation of GRP94-associated peptides, under conditions in which de novo synthesis of major histocompatibility complex class I molecules was inhibited, identified a post-endoplasmic reticulum compartment, accessed by mature major histocompatibility complex class I, as the predominant site of GRP94-associated peptide exchange onto major histocompatibility complex class I.     

Chaperone functions of the E3 ubiquitin ligase CHIP

The carboxyl terminus of the Hsc70-interacting protein (CHIP) is an Hsp70 co-chaperone as well as an E3 ubiquitin ligase that protects cells from proteotoxic stress. The abilities of CHIP to interact with Hsp70 and function as a ubiquitin ligase place CHIP at a pivotal position in the protein quality control system, where its entrance into Hsp70-substrate complexes partitions nonnative proteins toward degradation. However, the manner by which Hsp70 substrates are selected for ubiquitination by CHIP is not well understood. We discovered that CHIP possesses an intrinsic chaperone activity that enables it to selectively recognize and bind nonnative proteins. Interestingly, the chaperone function of CHIP is temperature-sensitive and is dramatically enhanced by heat stress. The ability of CHIP to recognize nonnative protein structure may aid in selection of slow folding or misfolded polypeptides for ubiquitination.     

A Diverse Assemblage of Reef Corals Thriving in a Dynamic Intertidal Reef Setting (Bonaparte Archipelago,Kimberley, Australia)

The susceptibility of reef-building corals to climatic anomalies is well documented and a cause of great concern for the future of coral reefs. Reef corals are normally considered to tolerate only a narrow range of climatic conditions with only a small number of species considered heat-tolerant. Occasionally however, corals can be seen thriving in unusually harsh reef settings and these are cause for some optimism about the future of coral reefs. Here we document for the first time a diverse assemblage of 225 species of hard corals occurring in the intertidal zone of the Bonaparte Archipelago, north western Australia. We compare the environmental conditions at our study site (tidal regime, SST and level of turbidity) with those experienced at four other more typical tropical reef locations with similar levels of diversity. Physical extremes in the Bonaparte Archipelago include tidal oscillations of up to 8 m, long subaerial exposure times (>3.5 hrs), prolonged exposure to high SST and fluctuating turbidity levels. We conclude the timing of low tide in the coolest parts of the day ameliorates the severity of subaerial exposure, and the combination of strong currents and a naturally high sediment regime helps to offset light and heat stress. The low level of anthropogenic impact and proximity to the Indo-west Pacific centre of diversity are likely to further promote resistance and resilience in this community. This assemblage provides an indication of what corals may have existed in other nearshore locations in the past prior to widespread coastal development, eutrophication, coral predator and disease outbreaks and coral bleaching events. Our results call for a re-evaluation of what conditions are optimal for coral survival, and the Bonaparte intertidal community presents an ideal model system for exploring how species resilience is conferred in the absence of confounding factors such as pollution.