Attentional selectivity,automaticity, and self-efficacy predict simulator-acquired skill transfer to the clinical environment

Introduction

Several studies demonstrated that simulator-acquired skill transfer to the operating room is incomplete. Our objective was to identify trainee characteristics that predict the transfer of simulator-acquired skill to the operating room.

SPECT gallium scanning for lymphoma and infection

Thirty gallium scans, using currently acceptable dosage levels (5-6 mCi) and a conventional rotating gamma camera, were performed on 20 patients with lymphoma or infection. Compared to planar scans, SPECT increased sensitivity and lesion detection from 48% to 89% in lymphoma, and from 50% to 80% in infection. The predictive value of a negative site was 81% in lymphoma and 67% in infection. Gallium utility is markedly increased by SPECT imaging. A normal gallium SPECT scan is highly accurate in ruling out disease.     

Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors.

CYP51 fulfills an essential requirement for all cells, by catalyzing three sequential mono-oxidations within the cholesterol biosynthesis cascade. Inhibition of fungal CYP51 is used as a therapy for treating fungal infections, whereas inhibition of human CYP51 has been considered as a pharmacological approach to treat dyslipidemia and some forms of cancer. To predict the interaction of inhibitors with the active site of human CYP51, a three-dimensional quantitative structure-activity relationship model was constructed. This pharmacophore model of the common structural features of CYP51 inhibitors was built using the program Catalyst from multiple inhibitors (n = 26) of recombinant human CYP51-mediated lanosterol 14alpha-demethylation. The pharmacophore, which consisted of one hydrophobe, one hydrogen bond acceptor, and two ring aromatic features, demonstrated a high correlation between observed and predicted IC(50) values (r = 0.92). Validation of this pharmacophore was performed by predicting the IC(50) of a test set of commercially available (n = 19) and CP-320626-related (n = 48) CYP51 inhibitors. Using predictions below 10 microM as a cutoff indicative of active inhibitors, 16 of 19 commercially available inhibitors (84%) and 38 of 48 CP-320626-related inhibitors (79.2%) were predicted correctly. To better understand how inhibitors fit into the enzyme, potent CYP51 inhibitors were used to build a Cerius(2) receptor surface model representing the volume of the active site. This study has demonstrated the potential for ligand-based computational pharmacophore modeling of human CYP51 and enables a high-throughput screening system for drug discovery and data base mining.     

A cluster of bacterial genes for anaerobic benzene ring biodegradation

A reductive benzoate pathway is the central conduit for the anaerobic biodegradation of aromatic pollutants and lignin monomers. Benzene ring reduction requires a large input of energy and this metabolic capability has, so far, been reported only in bacteria. To determine the molecular basis for this environmentally important process, we cloned and analyzed genes required for the anaerobic degradation of benzoate and related compounds from the phototrophic bacterium, Rhodopseudomonas palustris. A cluster of 24 genes was identified that includes twelve genes likely to be involved in anaerobic benzoate degradation and additional genes that convert the related compounds 4-hydroxybenzoate and cyclohexanecarboxylate to benzoyl-CoA. Genes encoding benzoyl-CoA reductase, a novel enzyme able to overcome the resonance stability of the aromatic ring, were identified by directed mutagenesis. The gene encoding the ring-cleavage enzyme, 2-ketocyclohexanecarboxyl-CoA hydrolase, was identified by assaying the enzymatic activity of the protein expressed in Escherichia coli. Physiological data and DNA sequence analyses indicate that the benzoate pathway consists of unusual enzymes for ring reduction and cleavage interposed among enzymes homologous to those catalyzing fatty acid degradation. The cloned genes should be useful as probes to identify benzoate degradation genes from other metabolically distinct groups of anaerobic bacteria, such as denitrifying bacteria and sulfate-reducing bacteria.     

Family history of alcoholism, youthful antisocial behavior and problem drinking among DWI offenders

This study assessed the impact of family history of alcoholism and antisocial behavior on problem drinking among male first-time DWI offenders. A sample of 123 men in DWI classes were assessed on demographic factors, antisocial behavior and family history of alcoholism. Also, measures of current and past drinking problems were assessed, including scales of perceived ability to control consumption, degree of physical dependence, occurrence of alcohol-related problems and preoccupation with alcohol. The results indicated that while family history of alcohol and antisocial behavior were not significantly related to quantity/frequency of alcohol consumption or alcohol-related problems, family history was related to drink duration. Main effects of family history and antisocial behavior were found for preoccupation with alcohol and physical dependence. There was a significant interaction with respect to perceived ability to control drinking. Results are discussed with regard to the implication that family history of alcoholism and antisocial behavior may influence the development of important precursors to alcoholism.     

Frontotemporal dementia and parkinsonism linked to chromosome 17 with the N279K tau mutation

We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course.     

Pharmacokinetics of indium-111-labeled B72.3 monoclonal antibody in colorectal cancer patients.

Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment. We determined mean time pharmacokinetic parameters for 11 patients entered in a Phase I/II clinical trial for detection of colorectal cancer. Patients were administered 0.5-2 mg of B72.3 anti-TAG-72 radiolabeled with 3.5-5 mCi of 111In, plasma activity was measured over time. Mean time pharmacokinetic parameters were (mean +/- s.e.m.): mean residence time; body (MRTB) 88.9 +/- 7.2 hr, central (MRTC) 73.8 +/- 6.0 hr; mean transit time, central (MTTC) 41.1 +/- 9.0 hr; mean residence time, periphery (MRTP) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPTP) 39.0 +/- 7.6 hr; mean transit time, periphery (MTTP) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and n compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRTC greater than MTTC and n much greater than 1. In patients without specific antigen, MRTC approximately equal to MTTC and n much less than 1. Pharmacokinetic studies may identify patients who do not have the tumor produced target antigen for the specific Mab and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis or treatment.