Use of a Checklist During Observation of a Simulated Cardiac Arrest Scenario Does Not Improve Time to CPR and Defibrillation Over Observation Alone for Subsequent Scenarios

Theory: Immersive simulation is a common mode of education for medical students. Observation of clinical simulations prior to participation is believed to be beneficial, though this is often a passive process. Active observation may be more beneficial. Hypotheses: The hypothesis tested in this study was that the active use of a simple checklist during observation of an immersive simulation would result in better participant performance in a subsequent scenario compared with passive observation alone. Methods: Medical students were randomized to either passive or active (with checklist) observation of an immersive simulation involving cardiac arrest prior to participating in their own simulation. Performance measures included time to cardiopulmonary resuscitation (CPR) and time to defibrillation and were compared between first and second scenarios as well as between passive and active observers. Results: Seventy-nine simulations involving 232 students were conducted. Mean time to CPR was 18 seconds (SD = 11.6) for those using the checklist and 24 seconds (SD = 15.8) for those who observed passively (M difference = 6 seconds), t(35) = 1.46, p =.153. Time to defibrillation was 94 seconds (SD = 26.4) for those using the checklist and 92 seconds (SD = 23.8) for those who observed passively (M difference = –2 seconds), t(38) =.21, p =.837. Time to CPR was 24 seconds (SD = 15.8) for passive observers and 31 seconds (SD = 21.0; M difference = 7 seconds), t(35) = 1.13, p =.265, for their first scenario counterparts. Time to CPR was 18 seconds (SD = 11.6) for active observers and 36 seconds (SD = 26.2; M difference = 18 seconds), t(24) = 2.81, p =.010, for their first scenario counterparts. Time to defibrillation was 92 seconds (SD = 23.8) for passive observers and 125 seconds (SD = 32.2; M difference = 33 seconds), t(33) = 3.63, p =.001, for their first scenario counterparts. Time to defibrillation was 94 seconds (SD = 26.4) for the active observers and 132 seconds (SD = 52.9; M difference = 38 seconds), t(28) =.46, p =.008, for their first scenario counterparts. Conclusions: Observation alone leads to improved performance in the management of a simulated cardiac arrest. The active use of a simple skills-based checklist during observation did not appear to improve performance over passive observation alone.     

Modeling of relationships between pharmacokinetics and blockade of agonist-induced elevation of intraurethral pressure and mean arterial pressure in conscious dogs treated with alpha(1)-adrenoceptor antagonists.

Fiduxosin is a new alpha(1)-adrenoceptor antagonist targeted for the treatment of symptomatic benign prostatic hyperplasia. The purpose of this study was to determine and compare the potencies of the alpha(1)-adrenoceptor antagonists terazosin, doxazosin, tamsulosin, and fiduxosin, based on relationships between plasma drug concentrations and blockade of phenylephrine (PE)-induced intraurethral (IUP) and mean arterial pressure (MAP) responses after single oral dosing in conscious male beagle dogs. Magnitude of blockade and plasma concentrations were evaluated at selected time points over 24 h. All drugs produced dose-dependent antagonism of PE-induced IUP and MAP responses. When IUP and MAP blockade effects were plotted against drug plasma concentrations, direct relationships were observed that were well described by the sigmoidal maximal effect model. IUP IC(50) values for terazosin, doxazosin, tamsulosin, and fiduxosin were 48.6, 48.7, 0.42, and 261 ng/ml, respectively. MAP IC(50) values were 12.2, 13.8, 1.07, and 1904 ng/ml, respectively. Uroselectivity index values, defined as MAP IC(50)/IUP IC(50), were 0.25, 0.28, 2.6, and 7.3, respectively. These results extend previous observations with terazosin in this model, showing that doxazosin exhibits a uroselectivity index comparable to terazosin, consistent with the lack of alpha(1)-adrenoceptor subtype selectivity or uroselectivity of these drugs. Tamsulosin, an alpha(1a)-/alpha(1d)-subtype selective agent, had an index value approximately 10-fold greater than the nonselective drugs. Based on its pharmacokinetic profile and a relative uroselectivity 29-fold greater than the nonselective drugs, fiduxosin is expected to exhibit greater selectivity for urethral compared with vascular alpha(1)-adrenoceptors in human and should be a novel, long-acting, uroselective alpha(1)-adrenoceptor antagonist.     

Patterns of expression of fibrinolytic genes and matrix metalloproteinase-9 in dissecting aortic aneurysms.

Although extensive tissue remodeling occurs during the various phases of aortic dissection, the underlying proteinases remain to be identified. Matrix metalloproteinase-9 (MMP-9) and components of the fibrinolytic system have been implicated in numerous tissue remodeling events and were therefore analyzed in surgical specimens of acute (n = 9), subacute (n = 4), and chronic (n = 7) aortic dissection by in situ hybridization. In the acute phase, intense plasminogen activator inhibitor 1 (PAI-1) gene expression was apparent in areas interfacing the dissecting hematoma, but no tissue-type PA (t-PA), urokinase-type PA (u-PA), or MMP-9 mRNAs were detected. Although PAI-1 mRNA was still present in the subacute phase, t-PA, u-PA, and MMP-9 mRNAs were now obvious, with PA gene expression co-localizing with areas of PAI-1 gene expression. In the chronic phase, PAI-1 mRNA was demonstrated around erythrocyte extravasations and surrounding bands of medial degeneration. However, there was little expression of PAs in these areas, and no MMP-9 was detected. Thus, fibrinolytic genes and MMP-9 are differentially expressed during the progression of aortic dissections. The kinetics of expression are consistent with acute fibrinolytic shutdown in response to the initial injury, a secondary subacute phase with active proteolysis, and finally, a chronic hypofibrinolytic state. Extensive neovascularization in the chronic phase may further reduce the physical stability of the dissected wall.     

Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity

LGR7 and LGR8 are G protein-coupled receptors that belong to the leucine-rich repeat-containing G-protein coupled receptor (LGR) family, including the thyroid-stimulating hormone (TSH), LH and FSH receptors. LGR7 and LGR8 stimulate cAMP production upon binding of the cognate ligands, relaxin and insulin-like peptide 3 (INSL3), respectively. We cloned several novel splice variants of both LGR7 and LGR8 and analysed the function of four variants. LGR7.1 is a truncated receptor, including only the N-terminal region of the receptor and two leucine rich repeats. In contrast, LGR7.2, LGR7.10 and LGR 8.1 all contain an intact seven transmembrane domain and most of the extracellular region, lacking only one or two exons in the ectodomain. Our analysis demonstrates that although LGR7.10 and LGR8.1 are expressed at the cell surface, LGR7.2 is predominantly retained within cells and LGR7.1 is partially secreted. mRNA expression analysis revealed that several variants are co-expressed in various tissues. None of these variants were able to stimulate cAMP production following relaxin or INSL3 treatment. Unexpectedly, we did not detect any direct specific relaxin or INSL3 binding on any of the splice variants. The large number of receptor splice variants identified suggests an unforeseen complexity in the physiology of this novel hormone-receptor system.     

Lipoblastoma and lipoblastomatosis in infancy and childhood: histopathologic, ultrastructural, and cytogenetic features

Lipoblastoma is a relatively rare tumor that occurs in infancy and early childhood and arises from embryonic white fat. Although a benign tumor, lipoblastomas tend to recur and may resemble myxoid liposarcoma. The authors report 26 cases over a 15-year period at Texas Children's Hospital. There was a slight female predilection (14F:12M). The most common symptom was a painless mass with or without increasing size. The trunk, extremities, head and neck, retroperitoneum, inguinal canal, peritoneal cavity, and lung were the tumor sites. Most tumors were circumscribed lipoblastomas and the minority were diffuse infiltrative lipoblastomatosis. Reexcision for residual or recurrent tumor was necessary more frequently in patients with lipoblastomatosis. Histopathologic examination and ultrastructural examination revealed cellular neoplasms composed of immature adipocytes with relatively well-defined septa, frequent lipoblasts, a fine vascular network, and often a myxoid appearance resembling myxoid liposarcoma. Cytogenetics was performed in 4 cases with chromosome 8q abnormality being most common. The major concern with lipoblastoma in children is to completely excise the tumor to avoid leaving residual tumor and to prevent recurrences. Confusion with myxoid liposarcoma, well-differentiated liposarcoma, and typical lipomas may occur. Although asymptomatic, lipoblastomas may cause dysfunction of other organ systems due to mass effect. Complete surgical excision with at least 2 years of follow-up is the preferred therapy.     

Histamine and calcitonin release from medullary thyroid carcinoma

The secretagogue effect of histamine on calcitonin secretion has been studied in 15 patients with medullary thyroid carcinoma and compared with known stimuli: glucagon and calcium in combination with pentagastrin. The effect of concomitant histamine H2-receptor blockade on these responses has been studied in the same patients. Seven patients with undetectable basal plasma calcitonin concentrations had measurable responses to calcium/pentagastrin but not to histamine or glucagon. In the remaining eight subjects, significant responses were seen to all three test substances, calcium/pentagastrin proving to be the most potent secretagogue. Establishment of H2-receptor blockade with cimetidine had no effect on basal calcitonin concentrations and did not suppress responses to histamine, calcium or pentagastrin. The variable secretagogue effect of histamine could be mediated through H1-receptors, through nonspecific vascular dilation "washing out" preformed calcitonin, or through its destruction to varying degrees by histaminase, present in most medullary thyroid tumors. Histamine is unlikely to replace calcium/pentagastrin as the most discriminative, provocative diagnostic agent in medullary thyroid carcinoma, but correlation of secretory responses with tissue histaminase concentrations and attempted blockade with differing antihistamines will further our understanding of this tumor.     

Transplantation of human prostatic carcinoma into nude mice in Matrigel

Previous successful transplantation of human primary prostatic carcinomas into nude mice has been described as "close to zero." When injected in Matrigel instead of culture medium, 25,000-fold fewer cells of the PC-3 human prostatic carcinoma cell line were required for the growth of tumors in nude mice during a 3-month period of observation; similar enhancement was observed with two other human prostatic carcinoma cell lines. Six of ten primary human prostatic carcinomas were transplanted successfully into nude mice when Matrigel was used as the vehicle.     

A Roadmap for Adapting an Evidence-Based HIV Prevention Intervention: Personal Cognitive Counseling (PCC) for Episodic Substance-Using Men Who Have Sex with Men

Episodic (less than weekly) drug use and binge drinking increase HIV-related sexual risk behaviors among men who have sex with men (MSM), yet no evidence-based interventions exist for these men. We describe an adaptation process of the Personalized Cognitive Counseling (PCC) intervention for utilization with high-risk, HIV-negative episodic, substance-using MSM. Participants (N?=?59) were racially diverse, and reported unprotected anal intercourse and concurrent binge drinking (85 %), use of poppers (36 %), methamphetamine (20 %) and cocaine (12 %). Semi-structured interviews with 20 episodic, substance-using MSM elicited sexual narratives for engaging in unprotected anal intercourse while using alcohol or drugs. Emergent qualitative themes were translated into self-justifications and included in a revised PCC self-justification elicitation instrument (SJEI). The adapted SJEI was pretested with 19 episodic, substance-using MSM, and the final adapted PCC was pilot-tested for acceptability and feasibility with 20 episodic, substance-using MSM. This process can be used as a roadmap for adapting PCC for other high-risk populations of MSM.