RESUMEN
There is a requirement in some beef markets to slaughter bulls at under 16 months of age. This requires high levels of concentrate feeding. Increasing the slaughter age of bulls to 19 months facilitates the inclusion of a grazing period, thereby decreasing the cost of production. Recent data indicate few quality differences in longissimus thoracis (LT) muscle from conventionally reared 16-month bulls and 19-month-old bulls that had a grazing period prior to finishing on concentrates. The aim of the present study was to expand this observation to additional commercially important muscles/cuts. The production systems selected were concentrates offered ad libitum and slaughter at under 16 months of age (16-C) or at 19 months of age (19-CC) to examine the effect of age per se, and the cheaper alternative for 19-month bulls described above (19-GC). The results indicate that muscles from 19-CC were more red, had more intramuscular fat and higher cook loss than those from 16-C. No differences in muscle objective texture or sensory texture and acceptability were found between treatments. The expected differences in composition and quality between the muscles were generally consistent across the production systems examined. Therefore, for the type of animal and range of ages investigated, the effect of the production system on LT quality was generally representative of the effect on the other muscles analysed. In addition, the data do not support the under 16- month age restriction, based on meat acceptability, in commercial suckler bull production.
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Dieta , Carne , Animales , Bovinos , Culinaria , Masculino , Carne/análisis , MúsculosRESUMEN
Acute heart failure (AHF) is one of the most important causes of mortality, morbidity and rising healthcare costs. Despite this, there has been minimal advancement in the management of AHF and the treatment continues to focus on symptomatic improvement using vasodilators, diuretics and inotropes, none of which have shown any mortality benefits. Though originally thought of as a reproductive hormone, relaxin is now recognized as a potent vasodilator that modulates systemic and renal vascular tone, resulting in pre- and after-load reduction and a decrease in cardiac workload. A single intravenous infusion of relaxin over 48 hours has been shown to provide significant dyspnea relief among AHF patients, with an ongoing study to evaluate its potential for mortality benefit. This article provides an insight into the pharmacology of this novel therapy for AHF with an eye towards future clinical applications.
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Insuficiencia Cardíaca/tratamiento farmacológico , Relaxina/uso terapéutico , Enfermedad Aguda , Humanos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Relaxina/efectos adversos , Relaxina/farmacocinética , Relaxina/farmacologíaRESUMEN
Organoids mirror in vivo tissue organization and are powerful tools to investigate the development and cell biology of the small intestine. However, their application for the study of host-pathogen interactions has been largely unexplored. We have established a model using microinjection of organoids to mimic enteric infection, allowing for direct examination of pathogen interactions with primary epithelial cells in the absence of confounding variables introduced by immune cells or the commensal microbiota. We investigated the impact of Paneth cell α-defensin antimicrobial peptides on bacterial growth. We demonstrate that organoids form a sealed lumen, which contains concentrations of α-defensins capable of restricting growth of multiple strains of Salmonella enterica serovar Typhimurium for at least 20 h postinfection. Transgenic expression of human defensin 5 in mouse organoids lacking functional murine α-defensins partially restored bacterial killing. We also found that organoids from NOD2(-/-) mice were not impaired in α-defensin expression or antibacterial activity. This model is optimized for the study of non-invasive bacteria but can be extended to other enteric pathogens and is amenable to further genetic manipulation of both the host and microbe to dissect this critical interface of host defense.
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Interacciones Huésped-Patógeno/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Intestino Delgado/inmunología , Intestino Delgado/microbiología , Animales , Proteínas Bacterianas/genética , Defensinas/genética , Defensinas/metabolismo , Técnicas de Inactivación de Genes , Interacciones Huésped-Patógeno/genética , Humanos , Metaloproteinasa 7 de la Matriz/genética , Metaloproteinasa 7 de la Matriz/metabolismo , Ratones , Ratones Noqueados , Mutación , Proteína Adaptadora de Señalización NOD2/genética , Salmonella typhimurium/genética , Salmonella typhimurium/inmunología , alfa-Defensinas/metabolismoRESUMEN
Recombinant human growth hormone (rhGH) therapy in Prader-Willi syndrome (PWS) causes increased basal metabolic rate and oxygen consumption, and hence increased ventilatory load. The case of an adolescent with PWS who experienced respiratory deterioration with an increase in rhGH and improvement with cessation of therapy is reported.
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Hormona de Crecimiento Humana/efectos adversos , Síndrome de Prader-Willi/tratamiento farmacológico , Insuficiencia Respiratoria/inducido químicamente , Adolescente , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Masculino , Polisomnografía , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéuticoRESUMEN
Prostate cancer continues to be the most commonly diagnosed malignancy in men of the western world. Its diagnosis, evaluation, and treatment therapies are constantly evolving. This paper summarizes and clarifies the most up-to-date information on prostate cancer prevention and treatment.
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Neoplasias de la Próstata/terapia , Humanos , MasculinoRESUMEN
We have reported previously that nonobese diabetic (NOD) fetal pancreas organ cultures lose the ability to produce insulin when maintained in contact with NOD fetal thymus organ cultures (FTOC). Initial studies indicated that exposure to glutamic acid decarboxylase (GAD65) peptides in utero resulted in delay or transient protection from insulin-dependent diabetes mellitus (IDDM) in NOD mice. We also found that exposure of young adult NOD mice to the same peptides could result in acceleration of the disease. To more closely examine the effects of early and late exposure to diabetogenic Ags on T cells, we applied peptides derived from GAD65 (GAD AA 246-266, 509-528, and 524-543), to our "in vitro IDDM" (ivIDDM) model. T cells derived from NOD FTOC primed during the latter stages of organ culture, when mature T cell phenotypes are present, had the ability to proliferate to GAD peptides. ivIDDM was exacerbated under these conditions, suggesting that GAD responsiveness correlates with the ivIDDM phenotype, and parallels the acceleration of IDDM we had seen in young adult NOD mice. When GAD peptides were present during the initiation of FTOC, GAD proliferative responses were inhibited, and ivIDDM was reduced. This result suggests that tolerance to GAD peptides may reduce the production of diabetogenic T cells or their capacity to respond, as suggested by the in utero therapies studied in NOD mice.
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Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/prevención & control , Glutamato Descarboxilasa/administración & dosificación , Glutamato Descarboxilasa/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Isoenzimas/administración & dosificación , Isoenzimas/inmunología , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/inmunología , Linfocitos T/inmunología , Adyuvantes Inmunológicos/farmacología , Secuencia de Aminoácidos , Animales , Animales Recién Nacidos/inmunología , Técnicas de Cocultivo , Diabetes Mellitus Tipo 1/enzimología , Diabetes Mellitus Tipo 1/etiología , Progresión de la Enfermedad , Relación Dosis-Respuesta Inmunológica , Femenino , Feto , Glutamato Descarboxilasa/farmacología , Esquemas de Inmunización , Inyecciones Intraperitoneales , Isoenzimas/farmacología , Activación de Linfocitos/efectos de los fármacos , Ratones , Ratones Endogámicos NOD , Datos de Secuencia Molecular , Técnicas de Cultivo de Órganos , Fragmentos de Péptidos/farmacología , Embarazo , Linfocitos T/efectos de los fármacosRESUMEN
BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN), a premalignant lesion of the prostate gland, is more common in black men than in white men. The influence of HGPIN on the serum prostate specific antigen (PSA) concentration is controversial, and correlations between HGPIN and PSA in black men and white men have not been investigated. METHODS: Between January 1992 and December 1998, 411 black men and 639 white men with suspected prostate carcinoma underwent an initial benign prostate biopsy at a single medical center. The presence or absence of HGPIN in the biopsy specimens was determined by one uropathologist. RESULTS: HGPIN was identified in 8.9% of the specimens. When stratified by PSA concentration (< 4.0 ng/mL, 4.0-9.9 ng/mL, and > or = 10.0 ng/mL), HGPIN was associated with an increased PSA concentration only among men with PSA concentrations < 4.0 ng/mL (P = 0.01). The prevalence of HGPIN in the black and white patients was 13.4% and 5.9%, respectively (P < 0.0001), and was significantly greater in black men than in white men with PSA concentrations < 4.0 ng/mL (P = 0.002). Among the patients with PSA concentrations < 4.0 ng/mL, black race was an independent predictor of an increased PSA concentration when adjusted for patient age, prostate volume, and the presence or absence of HGPIN (P = 0.03). CONCLUSIONS: HGPIN is more common in black men than in white men and may produce an increase in the PSA concentration. However, racial differences in the prevalence of HGPIN may not contribute to racial differences in PSA concentrations among men with no clinical or histologic evidence of carcinoma.
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Biopsia , Población Negra , Antígeno Prostático Específico/sangre , Neoplasia Intraepitelial Prostática/diagnóstico , Neoplasia Intraepitelial Prostática/etnología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/etnología , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Población BlancaRESUMEN
PURPOSE: Prostate cancer is more common in black than in white American men. Experience in a longitudinal prostate cancer screening program implies that cancer detection is greater in black than in white men with an abnormal digital rectal examination and prostate specific antigen (PSA) less than 4 ng./ml. We investigated potential racial differences in cancer detection in men treated in clinical practice who had an abnormal digital rectal examination and PSA less than 4 ng./ml. MATERIALS AND METHODS: Between January 1992 and December 1999 prostate biopsy was done at a Veterans Affairs Medical Center in 179 black and 357 white men with an abnormal digital rectal examination, PSA less than 4 ng./ml. and no history of prostate surgery. Significant racial differences in demographic and clinical parameters were limited to PSA, which was higher in black men (p = 0.01). RESULTS: Cancer was detected in 38 black (21%) and 65 white (18%) men (p = 0.42). There were no significant racial differences in the PSA adjusted cancer detection rate or in the Gleason score of detected disease. In men with PSA less than 1.0, 1.0 to 1.9, 2.0 to 2.9 and 3.0 to 3.9 ng./ml. the detection rate was 4%, 15%, 27% and 29%, respectively. CONCLUSIONS: In clinical practice prostate cancer detection appears to be equivalent in black and white men when an abnormal digital rectal examination is the only indication of malignancy.
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Negro o Afroamericano , Palpación , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/etnología , Población Blanca , Anciano , Biopsia con Aguja , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , RectoRESUMEN
The consensus view about the constitution of the T cell receptor repertoire has shifted greatly even during this decade. Although the discovery of autoimmunity in the fifties had clearly shown that a repertoire must exist directed against self antigens, the extent of this repertoire was not fully appreciated. In our work we have tried to elucidate the nature of the antigenic specificities against which this self-directed repertoire is directed. The non-tolerized (residual) self-directed repertoire is a direct consequence of the hierarchy of antigenic determinant display, and is the most important influence in the organism's choice of which T cells to delete. Certain determinants remain "silent" and are neither displayed in the thymus nor in the periphery: these are a heterogeneous group which are invisible to T cells for a variety of reasons. One reason relates to the processing and presentation of determinants, and a second derives from the nature of the T cell receptor (TcR) and the avidity of the T cell for its target specificity.
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Esclerosis Múltiple/inmunología , Neuroinmunomodulación/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Autotolerancia/inmunología , Linfocitos T/inmunología , Animales , Encefalomielitis Autoinmune Experimental/inmunología , HumanosRESUMEN
All adult BALB/c mice immunized with hen egg white lysozyme (HEL) or its dominant determinant, peptide (p)106-116, mount a T cell response using a "public" Vbeta8.2Jbeta1.5 T cell clone. Neonatal exposure to tolerance-inducing doses of antigen can drastically diminish responsiveness in the draining lymph nodes but not in the spleens of animals challenged as adults with the cognate antigen. To determine the role of T cell deletion or anergy within the mechanisms of observed neonatal "tolerance," we treated neonatal BALB/c mice with HEL and directly followed the characteristic public clone using complementarity determining region 3 length T cell repertoire analysis. Our results confirm that despite intraperitoneal injection of neonates with a high dose of HEL emulsified in incomplete Freund's adjuvant, a strong splenic proliferative response to HEL was observed upon recall. However, the adult splenic T cell response of these neonatally treated mice lacked the usual Vbeta8.2Jbeta1.5 public clone characteristic of HEL-primed BALB/c mice. After challenge with HEL-complete Freund's adjuvant as adults, immunoglobulin (Ig)G2a isotype antibody was drastically reduced, and IgG1 was found to be the predominant anti-HEL IgG isotype expressed, indicating a deviation of cytokine response toward T helper type 2. 5-wk-old mice, nasally instilled with tolerogenic doses of HEL p106-116, also showed significant inhibition of this public T cell expansion. These results demonstrate that during neonatal and adult nasal tolerance induction, deletion/anergy removes the public clone, exposing a response of similar specificity but that is characterized by the T helper type 2 phenotype and a splenic residence.
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Genes Codificadores de los Receptores de Linfocitos T , Tolerancia Inmunológica , Muramidasa/inmunología , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/inmunología , Administración Intranasal , Animales , Animales Recién Nacidos , Células Cultivadas , Pollos , Epítopos/administración & dosificación , Epítopos/inmunología , Femenino , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Muramidasa/administración & dosificación , Bazo/inmunologíaRESUMEN
BACKGROUND: Rearrangements of the antigen receptor genes in B and T cells generate products of unique length and sequence. Polymerase chain reaction (PCR) assays are routinely used to identify clonal lymphocyte populations by detecting clonal V-J rearrangements or chromosomal translocations within these antigen receptor loci. Multiple primer sets are, however, required to detect the majority of clonal B- and T-cell malignancies. Products from the individual reactions must be analyzed separately to avoid misinterpretation. Moreover, small clonal populations remain difficult to identify. To address these difficulties, we propose that an integrated fluorescence-based approach to clonal B- and T-cell detection would simultaneously identify both B- and T-cell neoplasia; increase amplicon resolution, analytic sensitivity, and assay throughput; produce more comprehensive and semiquantitative data useful for evaluation of hematologic malignancies; and eliminate labor intensive agarose and polyacrylamide gel electrophoresis. METHODS AND RESULTS: Samples were genomic DNA and cDNA. Differentially labeled primers were used to amplify regions diagnostic for B- and T-cell clonality in a single plate with a single thermocycler program. Combined amplicon products underwent capillary electrophoresis for high resolution fractionation and differential fluorescence detection and quantification. Data were automatically analyzed and archived. In a comparative analysis of a variety of clinical samples, this automated and integrated B- and T-cell assay showed >94% agreement (33 of 35 results) with individual B- and T-cell PCR assays. Furthermore, this assay had an overall monoclonality detection rate of 100%, and as little as 100 ng of sample DNA yielded complete B- and T-cell clonality test results. The limit of detection was approximately 10-2 cells, and amplicons were sized to within 0.1 basepair. Serial dilutions of clonal B- and T-cell lines comprising a coded proficiency panel were identified and correctly ranked. Specificity was 100% as determined by analysis of 18 control samples that were all negative for B- and T-cell clonality. CONCLUSIONS: Our data show that this automated and integrated B- and T-cell clonality assay system is a sensitive and specific tool useful for rapid identification of clonal lymphocyte populations and will likely have broad clinical applications.
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Linfocitos B/patología , Bioensayo , Linfocitos T/patología , Células Clonales , ADN Complementario/análisis , ADN Complementario/genética , Humanos , Sondas MolecularesRESUMEN
This paper introduces a model which incorporates fetal thymus organ culture (FTOC) from NOD mice to replicate thymic development of diabetogenic T cells. NOD fetal pancreas organ culture (FPOC) co-cultured with 13-16 day NOD FTOC for an additional 14-21 days produced less insulin than FPOC cultured alone. Insulin production from the FTOC of non-diabetic strains C57BL/6 and BALB/c was not inhibited by co-culture with FTOC from their syngeneic counterparts. Sections of the NOD co-cultures showed peri-islet infiltration with lymphocytes. Insulin reduction by FTOC/FP co-culture was prevented by co-culture of the NOD FT with FT from immunologically incompetent C.B-17 SCID/SCID mice. Co-culture of NOD FP with NOD FT prior to the development of T cells prevented generation of diabetogenic FTOC. Thus, early exposure of NOD T cell precursors to the thymic stromal elements of C.B-17 SCID/SCID FT or to islet antigens can negatively select for diabetogenic T cells or activate immuno-regulatory cells that can suppress diabetogenic T cell activity. The addition of blocking F(ab')2 fragments of anti-CD3epsilon monoclonal antibody to NOD FTOC/FP co-cultures prevented insulin reduction, implicating a role for TcR-mediated recognition in this "in vitro IDDM" model. The addition of activating whole anti-CD3epsilon caused the complete ablation of insulin production in FTOC/FP co-cultures from all strains tested. Transfer of unprimed syngeneic FTOC cells to prediabetic NOD mice prevented the onset of IDDM while transfer of islet-cell primed FTOC/FP cells slightly increased disease incidence. These data suggest that while diabetogenic T cells are present in the FT, they are normally suppressed, even after organ culture. However, these cells can induce the destruction of islet cells, in vitro and in vivo, if they are appropriately activated with pancreatic tissue.
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Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/patología , Técnicas de Cultivo de Órganos/métodos , Linfocitos T/citología , Linfocitos T/inmunología , Timo/citología , Timo/fisiología , Traslado Adoptivo , Animales , Anticuerpos/farmacología , Complejo CD3/inmunología , Diabetes Mellitus Tipo 1/prevención & control , Modelos Animales de Enfermedad , Embrión de Mamíferos , Femenino , Fragmentos de Inmunoglobulinas/farmacología , Insulina/biosíntesis , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones SCID , Páncreas/citología , Páncreas/metabolismo , Páncreas/fisiología , Embarazo , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T/efectos de los fármacos , Timo/inmunologíaRESUMEN
The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously. At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo. Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12.10% +/- 6.08 of standard; 2P < 0.05) and non-significantly lower factor VII coagulant activity (8.24% +/- 4.99 of standard) and fibrinogen concentrations (0.10 +/- 0.08 g. l-1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2.62 +/- 1.03 IU; 2P < 0.01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1.2, factor XII and C1 inhibitor). Total free fatty acid concentration was marginally significantly reduced (2P = 0.02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1.74 +/- 0.15 mmol.1(-1): 2P < 0.0001) but also in VLDL cholesterol (0.28 +/- 0.08 mmol.1(-1); 2P < 0.001) and IDL cholesterol (0.17 +/- 0.03 mmol.1(-1); 2P < 0.0001). There were also lower triglyceride levels associated with LDL (0.07 +/- 0.01 mmol.1(-1); 2P < 0.0001), IDL (0.03 +/- 0.01 mmol.1(-1); 2P < 0.01) and VLDL (0.27 +/- 0.14; 2P = 0.05). The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA reductase inhibitors (and of the newer fibrates which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.
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Ácidos Grasos no Esterificados/sangre , Hemostasis/efectos de los fármacos , Hipercolesterolemia/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Lipoproteínas/sangre , Lovastatina/análogos & derivados , Adulto , Anciano , Cromatografía en Capa Delgada , Enfermedad Coronaria/sangre , Enfermedad Coronaria/prevención & control , Ensayo de Inmunoadsorción Enzimática , Factor VII/efectos de los fármacos , Factor VII/metabolismo , Factor XII/efectos de los fármacos , Factor XII/metabolismo , Femenino , Fibrinógeno/efectos de los fármacos , Fibrinógeno/metabolismo , Estudios de Seguimiento , Humanos , Hidroximetilglutaril-CoA Reductasas/sangre , Hidroximetilglutaril-CoA Reductasas/efectos de los fármacos , Hipercolesterolemia/sangre , Lipoproteínas/efectos de los fármacos , Lovastatina/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Protrombina/efectos de los fármacos , Protrombina/metabolismo , Factores de Riesgo , Simvastatina , Método Simple CiegoRESUMEN
Educational imagery is a classroom teaching methodology that allows students to mentally isolate themselves and to use their natural abilities to daydream or fantasize in ways that accomplish educational objectives. Educational imagery is used to facilitate decision making, clarify values, memorize, incorporate behavioral outcomes of teaching, and reinforce cognitive concepts. The technique can help allied health students prepare for the clinical setting. The behavioral components, ethical concerns, and decision making that will occur in the clinical setting can be rehearsed in the classroom before the actual experience by guiding students' imagination. This article describes the nature of imagery and its sources, describes how to implement the strategy in the classroom, and gives examples of educational imagery strategies for the allied health disciplines.