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Background and objectives The purpose of this paper is to describe the use of resident performance on an observed structured clinical examination (OSCE) as a tool to refine a mood disorders curriculum, and to disseminate a mood disorders OSCE for use in other residency settings. Methods A depression-focused OSCE and a direct observation evaluation tool were developed and implemented. A total of 24 first-year family medicine residents (PGY1) participated in the OSCE, and their performance was used to direct changes in a mood disorders curriculum. Results Residents performed well on general interview behaviours, and 67% were able to uncover depression in a patient presenting with headaches. Less than 50% of the residents asked about suicidal ideation and recreational drug use. Curriculum was added that addressed the latter deficiencies. Conclusions Tracking of resident performance on specific behaviours during OSCE sessions can be used for curriculum evaluation purposes. The mood disorders curriculum in additional family medicine residency programmes can now be evaluated using our depression-focused OSCE and Clinical Performance Checklist.
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OBJECTIVE: Deep vein thrombosis (DVT) represents a major cause of morbidity in surgical patients. Controversial reports exist on the incidence of DVT in burn patients. We report our experience over a 10-year period. METHODS: Patients admitted to our Burn Unit over the period 1991-2001 and diagnosed with DVT were identified. Their records were retrospectively reviewed for demographic factors, extent and severity of burn injury and outcome. RESULTS: A total of 4102 patients were admitted to the WPH Burn unit during the study period. All patients received routine subcutaneous heparin prophylaxis. Ten patients were diagnosed with DVT (0.25%). Compared to our total burn population, these patients were older (mean age 47 +/- 22.7 years versus 35 +/- 22 years P = 0.14) and had more extensive burns (mean total body surface area (TBSA) 34.7 +/- 25.3% versus 12 +/- 15.7% P = 0.02). Two patients developed non-fatal pulmonary embolism (PE). There were three deaths, none due to thromboembolic disease. There were no complications from the routine administration of subcutaneous heparin. CONCLUSION: The incidence of DVT in our study is much less than the incidence reported in other critically ill patients and less than that of most reports on burn patients. In our experience, routine heparin prophylaxis is effective for the prevention of DVT in burn patients.
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Quemaduras/complicaciones , Trombosis de la Vena/etiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Superficie Corporal , Niño , Femenino , Heparina/administración & dosificación , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombosis de la Vena/prevención & controlRESUMEN
The extent to which plasma HDL concentration regulates reverse cholesterol transport (RCT) is not known. The principal acceptors of unesterified cholesterol (UC) from cultured cells are small pre-beta-HDL, which we have shown increase in plasma during intravenous infusion of apolipoprotein A-I/phosphatidylcholine (apoA-I/PC) discs in humans. We have now examined the effects on tissue fluid HDL and RCT. ApoA-I/PC or proapoA-I/PC discs were infused into 16 healthy males. Eleven had been given intravenous radiocholesterol to label tissue pools; in 12 prenodal leg lymph was collected throughout; and in 8 all feces were collected. The rise in small pre-beta-HDL in plasma was associated with increases in 1) pre-beta-HDL concentration in lymph (all subjects), 2) the size of other lymph HDL (four of four subjects), 3) the cholesterol content of lymph lipoproteins relative to plasma lipoproteins (P < 0.01, n = 4), 4) cholesterol-specific radioactivity in lymph (five of nine subjects), 5) plasma lathosterol (P < 0.004, n = 4), 6) plasma cholesterol esterification rate (P < 0.001, n = 4), and 7) fecal bile acid excretion (P < 0.001, n = 8). These results support the hypothesis that small pre-beta-HDL generated in plasma readily cross endothelium into tissue fluid, and thereby promote efflux of UC from peripheral cells. After delivery to the liver, peripheral cholesterol appears to be utilized more for bile acid synthesis than for biliary cholesterol secretion in humans.
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Apolipoproteína A-I/farmacología , Transporte Biológico/efectos de los fármacos , Líquidos Corporales/efectos de los fármacos , Colesterol/metabolismo , Lipoproteínas HDL/metabolismo , Fosfatidilcolinas/farmacología , Adulto , Apolipoproteína A-I/administración & dosificación , Apolipoproteína A-I/sangre , Apolipoproteína A-I/metabolismo , Apolipoproteínas/sangre , Apolipoproteínas/metabolismo , Ácidos y Sales Biliares/biosíntesis , Ácidos y Sales Biliares/metabolismo , Líquidos Corporales/metabolismo , Índice de Masa Corporal , Colesterol/sangre , Esterificación , Heces/química , Lipoproteínas de Alta Densidad Pre-beta , Humanos , Metabolismo de los Lípidos , Lípidos/sangre , Lipoproteínas HDL/sangre , Linfa/química , Linfa/metabolismo , Masculino , Fosfatidilcolinas/administración & dosificación , Factores de Tiempo , Triglicéridos/sangreRESUMEN
BACKGROUND AND OBJECTIVES: We examined the use of inexpensive handheld computers in documenting resident procedures. With a handheld computer, data is entered at the time of the procedure, eliminating the problem of double entry. METHODS: Connectivity and ease of use were important factors considered when choosing a handheld computer. All residents received a handheld computer for data entry. Residency staff downloaded the data to a desktop computer. At the same time, data useful to residents was placed on their devices. The process of generating individual and program reports required 2 hours of staff time each month. Survey data regarding use and acceptance by residents was collected. RESULTS: Eighty-eight percent of residents collected data on their handheld computer. Those residents responding to a survey felt that the handheld computer was "very useful," and 73% reported daily use. Initial costs were $310 per resident. CONCLUSIONS: Handheld computers streamlined the collection of procedure data for family practice residents. Handheld computers assisted in producing timely and useful procedural reports for both residents and the residency program. Additional uses of handheld computers were beneficial to the program and the residents.
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Computadores , Medicina Familiar y Comunitaria/educación , Internado y Residencia , Documentación , Humanos , WashingtónRESUMEN
Hep G2 cells were used to study the synthesis and secretion of phospholipid transfer protein (PLTP). Upon incubation of the cells at confluence with serum-free Dulbecco's modified Eagle's medium (DMEM), phosphatidylcholine (PC) transfer activity was found to accumulate in the culture media. The PC transfer activity in the media was effectively inhibited by rabbit anti-human PLTP immunoglobulin (Ig)G, thus indicating that the PC transfer activity was due to secreted PLTP. The molecular weight of Hep G2 PLTP was approximately 78 kDa by Western blot analysis, in agreement with the molecular weight obtained for purified human plasma PLTP. The PLTP secreted by Hep G2 also possessed an HDL conversion activity similar to that of human plasma PLTP. The addition of butyrate to the cell culture media resulted in a marked increase in the secretion of PLTP. After 24 h incubation with 4 mmol/L sodium butyrate, a more than twofold increase (P < 0.01) of PC transfer activity in the cell-conditioned media was obtained. The dose-dependent increase in the PC transfer activity in the media upon butyrate treatment was well correlated (r = 0.80, P < 0.01) with that of PLTP mass as determined by immuno-slot blot analysis of cell-conditioned media. The increased secretion of PLTP by Hep G2 treated with sodium butyrate was accompanied by a greater increase in the level of PLTP mRNA in the cells as determined by ribonuclease protection assay. In the presence of 4 mmol/L sodium butyrate, a fourfold increase (P < 0. 01) in mRNA level was obtained at 24 h. No stabilizing effect of butyrate on PLTP mRNA was apparent upon treatment of the cultured cells with the RNA synthesis inhibitor, actinomycin D. Thus, the up-regulatory effect of butyrate on PLTP gene expression seemed to have occurred at the transcriptional level.
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Ácido Butírico/farmacología , Proteínas Portadoras/metabolismo , Antagonistas de los Receptores Histamínicos/farmacología , Neoplasias Hepáticas Experimentales/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Transferencia de Fosfolípidos , Animales , Western Blotting , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Fosfatidilcolinas/metabolismo , ARN Mensajero/efectos de los fármacos , Conejos , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/metabolismo , Regulación hacia ArribaRESUMEN
No longer prescribed only for vegetative signs of depression, tricyclic antidepressants also lessen depressive cognitive distortions. Less clear is whether they ameliorate depressed patients' other cognitive deficits in memory, information processing speed, and psychomotor performance. We tested the alternative hypothesis that amitriptyline, because of its anticholinergic and sedative properties, would exacerbate depressed patients' cognitive disturbances. Depressed outpatients received double-blind placebo (n = 15), amitriptyline (n = 10), or clovoxamine fumarate (n = 10), a serotonin reuptake inhibitor relatively lacking in anticholinergic properties. Depression, memory, and psychomotor performance were assessed at baseline and after 7 and 28 days of drug treatment. Depression was alleviated after all treatments, including placebo. Only amitriptyline impaired performance on tests of memory, producing a significant decrement, relative to placebo, after 4 weeks of treatment. None of the treatments adversely affected performance on psychomotor tasks. These findings add to the evidence that antidepressant drugs with high anticholinergic activity can impair memory, despite alleviation of depression.
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Amitriptilina/uso terapéutico , Antidepresivos/uso terapéutico , Cognición/efectos de los fármacos , Trastorno Depresivo/psicología , Oximas/uso terapéutico , Estimulación Acústica , Adulto , Trastorno Depresivo/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Masculino , Memoria/efectos de los fármacos , Escalas de Valoración Psiquiátrica , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacosRESUMEN
Rats injected with Freund's adjuvant develop a syndrome resembling human rheumatoid arthritis complete with paw swelling, edema and persistent pain. At the onset of pain, arthritic rats and their pain-free littermate controls (vehicle injection) were allowed to self-administer intravenous morphine (5.0 mg/kg/injection) in a 24 hr/day schedule. Self-injected morphine appeared to provide analgesia in arthritic rats as demonstrated by a decreased sensitivity to applied tail pressure. Arthritic rats self-inject significantly less morphine than pain-free animals. Injection of indomethacin, which alleviates the pain and inflammation of the adjuvant-induced disease, reduces, at least initially, morphine self-injection in the arthritic but not pain-free animals. As the adjuvant-induced inflammation and pain dissipated, arthritic rats rapidly began to increase opioid intake. The presence of persistent pain apparently reduces the addictive properties of morphine.
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Artritis Experimental/fisiopatología , Artritis/fisiopatología , Morfina/administración & dosificación , Dolor/tratamiento farmacológico , Animales , Indometacina/farmacología , Masculino , Morfina/uso terapéutico , Ratas , Ratas Endogámicas , AutoadministraciónRESUMEN
The deoxyribonucleotide sequence has been determined for the regulatory region of the arginine F gene (argF) of Escherichia coli K-12. The location of the argF coding region was deduced by comparison of the DNA sequence to the sequence predicted from the primary structure of the N-terminus of the argF gene product, the subunit of the "F" isoenzyme of ornithine transcarbamylase. Transcription of the argF gene was found to initiate at a position approx. 40 bp preceding the N-terminal codon for OTCase. Comparison of the region surrounding the origin of transcription with a computer-generated "model promoter sequence" revealed structural similarities between the two sequences, in particular, the promoter-associated stretches known as the "Pribnow box" and "minus 35 contact site". Another feature noted for the argF promoter region was its extreme abundance of A : T nucleotide pairs. In the region preceding the start site for argF translation, a sequence was observed to be complementary to the 3' end of the 16S RNA component of the E. coli ribosome. Both the length and the nucleotide sequence of the argF leader region indicate that the argF gene does not contain an attenuator proposed to exist in other operons concerned with amino acid biosynthesis.
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Proteínas Bacterianas/genética , ADN Bacteriano/genética , Escherichia coli/genética , Ornitina Carbamoiltransferasa/genética , Secuencia de Bases , Enzimas de Restricción del ADN , Regulación de la Expresión Génica , Operón , Biosíntesis de Proteínas , Transcripción GenéticaAsunto(s)
Crithidia/análisis , ARN Ribosómico/análisis , Animales , Citoplasma/análisis , Peso Molecular , Ribosomas/análisisRESUMEN
The in vitro synthesis of enzymatically-active ornithine transcarbamylase (OTCase) directed by each of the E. coli K-12 OTCase genes (argF and argI) is described. The E. coli OTCase isoenzyme subunits are not identical, whether synthesized in vivo or in vitro, the argF-coded product being about 5% smaller. The OTCase protomers are enzymatically inactive but associate in vitro to an enzymatically active multimer. The rates of subunit association of argF and argI isoenzymes are considerably different. Utilizing the facile assay protocol presented, the regulation of in vitro OTCase synthesis by the specific holorepressor of the arginine regulon is demonstrated. Calculations based upon data presented indicate that there are about 65 molecules of argR gene product per bacterium, a substantially lower estimate than previously reported.
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Isoenzimas/biosíntesis , Ornitina Carbamoiltransferasa/biosíntesis , Arginina/metabolismo , Colifagos/genética , ADN Bacteriano , Escherichia coli/enzimología , Escherichia coli/genética , Genes , Genes Reguladores , Ornitina Carbamoiltransferasa/genética , Transducción GenéticaRESUMEN
The cell-free transcription of the argF and argI genes of the arginine biosynthetic regions is described using an S-30 system capable of coupled in vitro transcription-translation. Template DNA isolated from two independently isolated arginine transducing phages was used in this work. Steady state mRNA synthesis was observed which was attributed to RNAase degradation. Regulation of argF mRNA synthesis, directed by the argF gene carried on the specialized transducing phage phi80dargF is effected to the extent of at least 95% by the arginine holorepressor at the transcriptional stage and at least 80% of the regulation of the expression of the argI gene is mediated at the transcriptional stage. Evidence is presented which indicates that the arginine holorepressor prevents RNA polymerase from binding to the arginine promoter and suggests that the operator and promoter sites may overlap.
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Arginina/biosíntesis , ADN Viral/metabolismo , Escherichia coli/genética , Genes Virales , Transcripción Genética , Sistema Libre de Células , Colifagos , Escherichia coli/metabolismo , Mutación , Biosíntesis de Proteínas , ARN Bacteriano/metabolismo , ARN Mensajero/biosíntesisRESUMEN
Two mutations restricting the leakiness of an amber mutant are described. They were selected without the use of streptomycin: one maps in the strA region (at 64 minutes of the current E. coli chromosomal map) but is streptomycin sensitive and the other in the threonine region (at the origin of the map), 23% cotransducible with threonine by P1.
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Escherichia coli , Mutación/efectos de los fármacos , Mapeo Cromosómico , Cromosomas Bacterianos , Genes , Ribosomas , Estreptomicina/farmacologíaRESUMEN
Evidence is presented suggesting that streptomycin binds to 16S RNA or to 30S ribosomal subunits at the same topographical site located on the RNA chain. The equally bactericidal dihydrostreptomycin binds to the same site as streptomycin but with lower affinity. The effect of drug binding to 16S RNA (measured by reconstitution inhibition) is readily reversible, while that of drug binding to 30S subunits (measured by misreading) persists after removal of the drug. Binding of the drug is not a necessary and sufficient reason for killing.
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Sulfato de Dihidroestreptomicina/metabolismo , Escherichia coli/metabolismo , ARN Bacteriano/metabolismo , ARN Ribosómico/metabolismo , Ribosomas/metabolismo , Estreptomicina/metabolismo , Radioisótopos de Carbono , Fraccionamiento Celular , Escherichia coli/ultraestructura , Genotipo , Fenotipo , TritioRESUMEN
Translational leakiness (i.e., nonspecific suppression) of nonsense mutants of bacteriophage T4 is increased in cells of certain streptomycin-resistant strains previously grown in the presence of streptomycin. Concomitantly, ribosomes extracted from these streptomycin-grown cells possess a high level of misreading. Increased suppression ability as well as ribosomes that highly misread accumulate with kinetics expected for a constant differential rate of synthesis of a new product induced by drug action. The misreading ribosomes do not contain appreciable amounts of streptomycin and the misreading property is lost by exposure to high salt concentrations. It is suggested that streptomycin (or dihydrostreptomycin, or paromomycin) induces a reversible modification in 30S subunit assembly without physically participating in the modified structure. The extent of this modification appears dependent upon the strA allele.
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Escherichia coli/efectos de los fármacos , Ribosomas/efectos de los fármacos , Estreptomicina/farmacología , Proteínas Bacterianas/biosíntesis , Colifagos , Escherichia coli/citología , Lisogenia , Mutación , Biosíntesis de Proteínas/efectos de los fármacos , Ribosomas/metabolismo , Transducción GenéticaRESUMEN
The functional peculiarities of ram mutants correlate with an observed alteration in chromatographic mobility of P4(a), a specific protein of the 30S ribosomal subunit. This finding is supported by ribosomal reconstitution experiments. These facts, together with the known location of the ram mutational site in the vicinity of other 30S genetic determinants, suggest that ram is the structural gene for P4(a). The known contrasting roles of ram and strA in determining translational efficiency require that the function of P4(a) should be explained in relation to P10 (the 30S-subunit protein defined by strA). One consequence of altering P4(a), a key protein in ribosome assembly, might be to change the interaction of P10 with the 30S subunit. The functional interrelationship of P4(a) and P10 is discussed in terms of the possible roles of these two proteins in regulating access of tRNA molecules to the decoding site.
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Proteínas Bacterianas/análisis , Escherichia coli , Biología Molecular , Mutación , Ribosomas/análisis , Autorradiografía , Isótopos de Carbono , Cromatografía , Escherichia coli/citología , Genes , Genotipo , ARN Ribosómico/análisis , TritioRESUMEN
Chemical modification of ribosomes from Escherichia coli by oxidation in the presence of selected photosensitizing dyes causes a rapid loss of their amino acid-incorporating ability. By comparing the efficiency of dyes that sensitize the photooxidation of either guanine in ribonucleic acid or amino acid residues in proteins, inactivation of one or more functional ribosomal proteins is inferred.