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BACKGROUND: Glucagon and glucagon-like peptide-1 (GLP-1) are evolutionarily related anorectic hormones. Glucagon also increases energy expenditure. The combination of glucagon and GLP-1 could cause weight loss through a simultaneous reduction in food intake and increased energy expenditure. However, the effect of combined administration of glucagon and GLP-1 on food intake and neuronal activation has not previously been studied. Furthermore, the effect of glucagon on neuronal activation in appetite regulating centres has not been assessed. Characterisation of the effects of glucagon when administered singly and in combination with GLP-1 on neuronal activation will be important for determining the mechanism of action of related potential antiobesity therapies. OBJECTIVES: To investigate the effects of peripherally administered GLP-1 and glucagon on food intake, neuronal activation and blood glucose in mice when administered individually and in combination. METHODOLOGY: Food intake, blood glucose and c-fos expression in the hypothalamus, amygdala and brainstem were measured in response to GLP-1 and glucagon, alone and in combination. RESULTS: Peripherally administered GLP-1 and glucagon decreased food intake and increased c-fos expression in the brainstem and amygdala. Doses of GLP-1 and glucagon that individually did not significantly affect feeding, in combination were anorectic and stimulated neuronal activation in the area postrema (AP) and central nucleus of the amygdala. Combined administration of GLP-1 and glucagon prevented the acute hyperglycemic effect of glucagon alone. CONCLUSION: Anorectic doses of glucagon and GLP-1 induced similar patterns of c-fos expression. Combined administration of low dose GLP-1 and glucagon inhibited food intake and induced c-fos expression in the AP and amygdala. The combination of both hormones may offer the opportunity to utilise the beneficial effects of reduced food intake and increased energy expenditure, and may therefore be a potential treatment for obesity.
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Amígdala del Cerebelo/metabolismo , Apetito/fisiología , Tronco Encefálico/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Glucagón/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Apetito/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ingestión de Alimentos/efectos de los fármacos , Metabolismo Energético , Glucagón/farmacología , Péptido 1 Similar al Glucagón/farmacología , Inyecciones Intraperitoneales , Masculino , Ratones , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacosRESUMEN
We here present the case of a rarely seen anomalous origin and retropulmonary course of the left circumflex artery from the proximal right coronary artery. The patient suffered from coronary ischemia due to stenotic lesions both in the aberrant circumflex coronary artery and in the first and second diagonal branches. Coronary bypass operation was performed.
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OBJECTIVE: To assess the knowledge of polio detection and notification by front-line clinicians in Egypt. METHODS: This study examines clinicians' knowledge and awareness of polio detection and notification using a multiple-choice questionnaire (maximum score=43) in three large health care centres in central Cairo (n=52). RESULTS: The results reveal a significant variation of knowledge amongst doctors, with junior and senior house officers scoring an average of 30.6 (95% CI: 29.5-31.7), specialist registrars and consultant paediatricians 30.3 (CI 28.9-31.7), and public health doctors 35.4 (CI 32.9-36.8). Mean total scores of public health doctors were significantly higher than those of other clinicians. Senior paediatricians performed no better than newly qualified doctors. CONCLUSIONS: The results suggest that there is a need for more clinical teaching and training amongst junior doctors as well as senior clinicians and consultants. Appropriate knowledge of diagnosing AFP and of the correct protocol amongst clinicians is essential to maintain the high quality of the WHO programme in Egypt.
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Competencia Clínica , Parálisis/virología , Poliomielitis/diagnóstico , Enfermedad Aguda , Egipto , Humanos , Cuerpo Médico de Hospitales/normas , Hipotonía Muscular/virología , Poliomielitis/complicaciones , Vigilancia de la Población , Salud Pública/normasRESUMEN
BACKGROUND: On April 22, 2004, the Assisted Human Reproduction Act came into force, prohibiting the purchase of sperm or eggs from donors in Canada. In response to the concerns of medical professionals and some consumers that prohibiting payment would lead to a decline in the number of gamete donors, Health Canada commissioned research on altruistic donor recruitment and recruitment strategies. METHODS: Twenty-two studies of sperm donors were located and their findings reviewed. The studies spanned 23 years (1980-2003), were undertaken in a range of countries, and were chosen on the merit of their relevance to the development of recruitment strategies within a policy of altruistic sperm donation. Observations were derived from assessing and comparing the purposes, findings, and implications of the 22 studies. RESULTS: Payment for providing sperm was made in all but three studies, although participants in 15 studies indicated clearly that their motivations were primarily altruistic. Observations indicate that men who are more willing to be identified to offspring in the future share demographic characteristics, such as age and parental status, with those who are prepared to donate altruistically. These characteristics appear to be a factor in motivation to donate altruistically. CONCLUSION: The studies show that there are men who are prepared to donate sperm without financial payment. The findings suggest that a change is required in the culture of sperm donation, specifically the adoption of a new approach to donor recruitment.
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Política de Salud , Técnicas Reproductivas Asistidas/legislación & jurisprudencia , Espermatozoides , Donantes de Tejidos , Altruismo , Actitud , Investigación Biomédica , Canadá , Economía , Femenino , Política de Salud/legislación & jurisprudencia , Humanos , Masculino , Donantes de Tejidos/legislación & jurisprudencia , Donantes de Tejidos/psicología , VoluntariosAsunto(s)
Neoplasias Pulmonares/diagnóstico , Melanoma/diagnóstico , Tomografía de Emisión de Positrones , Anciano , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Colecistitis/diagnóstico , Reacciones Falso Positivas , Humanos , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Melanoma/secundario , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND: Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) has become an important tool in the postoperative management of de-differentiated thyroid cancer. The utility of this imaging modality in the preoperative assessment of thyroid nodules is unclear. This study was designed to determine whether (18)FDG-PET/CT improves the preoperative diagnosis of thyroid nodules. METHODS: A total of 31 patients with 48 lesions underwent fine-needle aspiration and (18)FDG-PET/CT before surgical resection of thyroid nodules. PET/CT images were obtained 1 hour after intravenous administration of (18)FDG. Standard uptake values were calculated for regions of increased (18)FDG uptake. CT scans were evaluated to identify thyroid pathology. Final pathologic diagnoses were compared with PET/CT findings. RESULTS: Fifteen of 48 lesions were malignant and 33 were benign. Nine of 15 malignant lesions were (18)FDG-avid (sensitivity 60%). Thirty of 33 benign lesions were (18)FDG-cold (specificity 91%). Positive and negative predictive values were 75% and 83%, respectively. CONCLUSIONS: (18)FDG-PET/CT provides a high negative predictive value for malignancy, making this a potentially useful tool in the evaluation of thyroid nodules with indeterminate fine-needle aspiration. However further studies with larger sample sizes are needed to determine the true efficacy of this test.
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Nódulo Tiroideo/diagnóstico por imagen , Adulto , Anciano , Femenino , Fluorodesoxiglucosa F18 , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Sensibilidad y Especificidad , Nódulo Tiroideo/cirugía , Tiroidectomía , Tomografía Computarizada por Rayos XRESUMEN
Adverse effects of wound healing, such as excessive scar tissue formation, wound contraction, or nonhealing wounds represent a major clinical issue in today's healthcare. Transforming growth factor (TGF)-beta3 has specifically been implicated in wound healing. Our hypothesis was that local administration of TGF-beta3 to excisional dermal wounds would diminish wound contraction and scar formation. Microtextured wound covers, containing different concentrations of TGF-beta3, were placed onto full-thickness excisional skin wounds in guinea pigs. Tattooed reference marks were used to quantify wound contraction. Sixty-four male guinea pigs in four study groups (5 ng TGF-beta3, 50 ng TGF-beta3, no growth factor, sham wound) were followed for up to 6 weeks. We analyzed 19 different parameters of wound healing. Results showed that, in some instances, the 50-ng TGF-beta3 group gave less contraction, whereas the 5-ng TGF-beta3 group gave more contraction. These differences confirm that TGF-beta3 has an optimum working concentration, and suggest this concentration to be closer to 50 ng than to 5 ng TGF-beta3. However, only very few significant differences occurred, and thus we conclude that the clinical relevance of our findings is negligible. Earlier studies, reporting clinically improved wound healing by TGF-beta3, could therefore not be confirmed by this study.
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Materiales Biocompatibles/química , Piel/metabolismo , Piel/patología , Factor de Crecimiento Transformador beta/metabolismo , Cicatrización de Heridas , Actinas/metabolismo , Animales , Materiales Biocompatibles/metabolismo , Cobayas , Humanos , Masculino , Regeneración/fisiología , Siliconas/metabolismo , Piel/citología , Propiedades de Superficie , Factor de Crecimiento Transformador beta/química , Factor de Crecimiento Transformador beta3RESUMEN
We sought to investigate the utility of stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the identification of coronary artery disease (CAD) in the distribution of first-order branch vessels. We evaluated 135 consecutive patients with coronary angiography and stress SPECT MPI. We anatomically matched angiography and SPECT to assess the sensitivity, specificity and accuracy of SPECT MPI for the detection of CAD in the distribution of first-order branches. Subgroup analysis for stress test performance and previous coronary artery bypass grafting (CABG) was also performed. The sensitivity, specificity and accuracy of stress SPECT MPI for the detection of CAD in the distribution of first-order branch vessels were all 67%. For isolated branch vessel CAD, stress SPECT MPI had a sensitivity of 44%. In patients without CABG, the sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order branch vessels were 71%, 67% and 68%, compared with 60%, 67% and 64% for patients with CABG. The sensitivity for isolated branch vessel CAD was 50% for patients without CABG, but only 29% for patients with CABG. The sensitivity and specificity for CAD in the distribution of branch vessels were similar for all patients for all stress test modalities and heart rate response (sensitivity, 64-69%; specificity, 61-69%). Stress SPECT MPI offers intermediate sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order coronary artery branch vessels. However, for isolated branch vessel CAD, stress SPECT has a lower sensitivity, particularly in patients with previous CABG.
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Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Prueba de Esfuerzo , Técnica de Sustracción , Tomografía Computarizada de Emisión de Fotón Único/métodos , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como AsuntoRESUMEN
In both normal and disturbed wound healing, the generation of large, contracting scars can raise serious functional and cosmetic problems. A possible strategy to minimize or avoid the generation of scar tissue surrounding an implant is to apply transforming growth factor-beta(3) (TGF-beta(3)) to the implant. TGF-beta(3) (0, 1, or 2.5 microg) was freeze-dried onto poly-L-lactic acid (PLA) microgrooved substrates (width, 10 microm; depth, 1 microm) and implanted subcutaneously on the backs of rats for 2 and 8 weeks. After sacrifice, implants and surrounding tissue were histologically processed. Light microscopic and histomorphometric evaluation of capsule thickness, capsule quality, and implant-tissue interface was performed. In addition, we stained for alpha-smooth muscle actin (SMA), collagen, and ED-1 (a monocyte-macrophage marker). All implants were surrounded by a fibrous capsule. Capsules of the implants loaded with 1 or 2.5 microg of TGF-beta(3) showed significantly higher capsule quality. This meant that capsules were more mature compared with implants without TGF-beta(3). However, no significant differences were found in terms of thickness of the capsules or quality of the interface. Finally, apparently significant differences were also found in the expression of alpha-SMA, when comparing the various growth factor concentrations at both implantation points. In conclusion, the use of microgrooved PLA substrates with TGF-beta(3) did not lead to an overall improvement of periimplant tissue healing.
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Ácido Láctico/metabolismo , Polímeros/metabolismo , Prótesis e Implantes , Factor de Crecimiento Transformador beta/metabolismo , Actinas/metabolismo , Animales , Colágeno/metabolismo , Macrófagos/metabolismo , Masculino , Poliésteres , Ratas , Ratas Wistar , Factor de Crecimiento Transformador beta3 , Cicatrización de Heridas/fisiologíaRESUMEN
Transforming growth factor beta(3) (TGF-beta(3)) has been under investigation with the objective of improving wound healing. Yet, little experimental knowledge exists about applications of TGF-beta(3) in implantology and tissue engineering. The aims of this study were to determine the release kinetics and bioactivity of TGF-beta(3) released from microtextured silicone and poly-L-lactic acid (PLA) surfaces in vitro and in vivo. We loaded surfaces with 100 ng of TGF-beta(3). An in vitro assay showed that TGF-beta(3) was released in a burstlike manner. Released TGF-beta(3) was capable of inhibiting the proliferation of mink lung epithelial cells, indicating that released TGF-beta(3) had remained at least partly active. Subsequently, an in vivo experiment (1 h-3 days) was performed with implants loaded with TGF-beta(3). In cryosections, TGF-beta(3) activity was assessed by an in situ bioassay. We found that active TGF-beta(3) was released for up to 24 h. Furthermore, released TGF-beta(3) could be detected up to 320 microm from the implant. On the basis of these observations, we conclude that TGF-beta(3) loaded onto microtextured polymer membranes remains functional when released in vitro and in vivo and, therefore, may represent an alternative for introducing a growth factor into a wound to achieve long-term and long-range biological effects.
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Materiales Biocompatibles , Ácido Láctico/metabolismo , Polímeros/metabolismo , Siliconas/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Epitelio/metabolismo , Técnicas In Vitro , Cinética , Pulmón/metabolismo , Visón , Poliésteres , Factor de Crecimiento Transformador beta3RESUMEN
Here we aimed to compare the tissue reaction to smooth and micro-grooved implants, at different implantation sites. We hypothesised that subperiosteally less mobility is to be expected between an implant and the surrounding tissue, which can lead to a more subdued tissue response. In addition, we hypothesised that a similar effect can be reached when substrata are equipped with micro-grooves. Poly-L-lactic acid smooth or micro-grooved surfaces (width 2 or 10 microm, depth 1 microm) were implanted subperiosteally on the frontal bone of the skull, or subcutaneously in the flanks of goats for 2, 4 and 12 weeks. After sacrifice, implants and surrounding tissue were histologically processed. Light microscopical and histomorphometrical evaluation of the histomorphometrical analyses, capsule thickness, capsule quality and implant-tissue interface was performed. In addition, we stained for alpha-smooth muscle actin. collagen and CD-68 expression. All implants were surrounded by a fibrous capsule. Capsules around subperiosteal implants were more matured than around subcutaneous implants. In time, capsule thickness significantly decreased around subperiosteal implants, but increased around subcutaneous implants. Also, nowhere differences were found in the presence of collagen or alpha-smooth muscle actin. The interfacial cells around all implants frequently showed staining for the monocyte-macrophage marker CD-68. We concluded that in this model, decreased mobility of an implant relative to the surrounding tissue did positively influence the peri-implant tissue response, but the applied surface topography did not.
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Materiales Biocompatibles , Huesos/metabolismo , Reacción a Cuerpo Extraño , Prótesis e Implantes , Actinas/biosíntesis , Animales , Antígenos CD/biosíntesis , Antígenos de Diferenciación Mielomonocítica/biosíntesis , Compuestos Azo/farmacología , Colágeno/biosíntesis , Colorantes/farmacología , Femenino , Cabras , Inmunohistoquímica , Inflamación , Inyecciones Subcutáneas , Ácido Láctico/metabolismo , Músculo Liso/metabolismo , Poliésteres , Polímeros/metabolismo , Piel/metabolismo , Cráneo/metabolismo , Factores de TiempoRESUMEN
Cis-aminoindanol, a key chiral precursor to the HIV protease inhibitor CRIXIVAN, can be derived from indene oxidation products of (2R) stereochemistry. A number of different microorganisms, notably strains of the genera Pseudomonas and Rhodococcus, have been isolated that catalyze the oxygenation of indene to indandiol with greater stereospecificity than is achievable through traditional chemical synthesis. The yield and ultimate optical purity of indandiol produced in such biocatalytic processes is influenced by the intrinsic stereospecificity of the oxygenase(s), enantioselective dehydrogenation, and the loss of substrate to alternate, undesirable metabolites. Metabolic engineering of any indene bioconversion system for the commercial-scale production of cis-aminoindanol must account for these influences, as well as pathway fluxes and enzyme regulation, to optimize the formation of oxygenated precursors with useful stereochemistry. As such, the process by which bacterial systems carry out the bioconversion of indene to indandiol serves as a model for biological production of industrially relevant chiral synthons.
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Ingeniería Genética/métodos , Indanos/metabolismo , Indenos/metabolismo , Pseudomonas putida/enzimología , Rhodococcus/enzimología , Biotecnología/métodos , Inhibidores de la Proteasa del VIH/química , Inhibidores de la Proteasa del VIH/metabolismo , Indinavir/química , Indinavir/metabolismo , Oxigenasas/genética , Oxigenasas/metabolismo , Pseudomonas putida/genética , Rhodococcus/genéticaRESUMEN
From in vitro studies it is known that a plasma-treatment can enhance cell spreading. Similar effects can be observed after pretreatment of the surface with a protein coating, to mediate cell adhesion. The aim of the current study was to evaluate the in vivo effects of these surface modifications, in a three-month experiment in a goat model. We made silicone and poly-L-lactic acid implants with double-sided parallel micro-grooves (depth 1.0 microm, width 10.0 microm), a random surface roughness, or a smooth surface. Implants either received a radio-frequency glow discharge (RFGD) treatment, a fibronectin (Fn) pre-coating, or no pre-treatment. Subsequently, they were inserted into subcutaneous pockets created on the flanks of goats for 1, 3 or 12 weeks. Histological analysis showed that a fibrous tissue capsule had formed around all implants. Histomorphometrical analysis was performed on capsule thickness, capsule quality and the implant-tissue interface quality. Fn-treated surfaces showed a considerable early inflammatory reaction. Besides this, RFGD treatment or Fn pre-coating did not further influence any of the measured parameters. In conclusion, pre-treatment of polymer implant surfaces with Fn or RFGD treatment did not significantly influence tissue reaction around implants with micro-grooved, roughened or smooth surfaces.
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Materiales Biocompatibles/toxicidad , Tejido Conectivo/efectos de los fármacos , Fibronectinas , Ácido Láctico/toxicidad , Polímeros/toxicidad , Siliconas/toxicidad , Animales , Adhesión Celular , Tejido Conectivo/patología , Femenino , Cabras , Ensayo de Materiales , Poliésteres , Prótesis e Implantes , Ondas de Radio , Propiedades de Superficie , Factores de TiempoRESUMEN
Tissue reaction to biomaterials is dependent on properties such as surface topography. The aim of this study was to evaluate the tissue reaction around implants with different surface topographies. We made coin-shaped silicone and poly-L-lactic acid (PLLA) implants with double-sided parallel microgrooves (depth 1.0 microm; width 10.0 microm) and random roughness on a micrometer scale. The control implants were smooth. These implants were inserted into subcutaneous pockets created on the flanks of goats. After 1, 3, or 12 weeks, the goats were sacrificed and the implants retrieved and histologically processed. Light microscopic evaluation revealed the formation of fibrous tissue capsules around all implant materials. The PLLA did not visibly degrade during the study period. Histomorphometric analyses were performed on capsule thickness, capsule quality, and on the implant-tissue interface quality. Compared with the silicone implants, the capsules around the PLLA implants showed significantly better capsule quality. Compared to the smooth implants, the capsules around the microgrooved implants were thicker, but the capsules around the roughened implants were thinner. However, randomly roughened implant surfaces generally elicited a stronger and more prolonged inflammatory reaction compared to smooth and microgrooved implant surfaces. We conclude that the application of microgrooves or random surface roughness to polymer implants apparently does not have beneficial effects on peri-implant tissue healing.
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Materiales Biocompatibles , Reacción a Cuerpo Extraño , Ácido Láctico , Polímeros , Prótesis e Implantes , Siliconas , Animales , Materiales Biocompatibles/química , Femenino , Cabras , Ácido Láctico/química , Poliésteres , Polímeros/química , Distribución Aleatoria , Siliconas/química , Piel/citología , Propiedades de SuperficieRESUMEN
Huntington's disease (HD) is a dominant neurodegenerative disease caused by polyglutamine (polyQ) expansion in the protein huntingtin (htt). HD pathogenesis appears to involve the production of mutated N-terminal htt, cytoplasmic and nuclear aggregation of htt, and abnormal activity of htt interactor proteins essential to neuronal survival. Before cell death, neuronal dysfunction may be an important step of HD pathogenesis. To explore polyQ-mediated neuronal toxicity, we expressed the first 57 amino acids of human htt containing normal [19 Gln residues (Glns)] and expanded (88 or 128 Glns) polyQ fused to fluorescent marker proteins in the six touch receptor neurons of Caenorhabditis elegans. Expanded polyQ produced touch insensitivity in young adults. Noticeably, only 28 +/- 6% of animals with 128 Glns were touch sensitive in the tail, as mediated by the PLM neurons. Similar perinuclear deposits and faint nuclear accumulation of fusion proteins with 19, 88, and 128 Glns were observed. In contrast, significant deposits and morphological abnormalities in PLM cell axons were observed with expanded polyQ (128 Glns) and partially correlated with touch insensitivity. PLM cell death was not detected in young or old adults. These animals indicate that significant neuronal dysfunction without cell death may be induced by expanded polyQ and may correlate with axonal insults, and not cell body aggregates. These animals also provide a suitable model to perform in vivo suppression of polyQ-mediated neuronal dysfunction.
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Axones , Caenorhabditis elegans/metabolismo , Neuronas Aferentes/fisiología , Péptidos/metabolismo , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/citología , Muerte Celular , Proteínas Fluorescentes Verdes , Enfermedad de Huntington/metabolismo , Enfermedad de Huntington/patología , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Microscopía FluorescenteRESUMEN
Several models of left ventricular segmentation have been developed that assume a standard coronary artery distribution, and are currently used for interpretation of single-photon emission tomography (SPET) myocardial perfusion imaging. This approach has the potential for incorrect assignment of myocardial segments to vascular territories, possibly over- or underestimating the number of vessels with significant coronary artery disease (CAD). We therefore sought to validate a 17-segment model of myocardial perfusion by comparing the predefined coronary territory assignment with the actual angiographically derived coronary distribution. We examined 135 patients who underwent both coronary angiography and stress SPET imaging within 30 days. Individualized coronary distribution was determined by review of the coronary angiograms and used to identify the coronary artery supplying each of the 17 myocardial segments of the model. The actual coronary distribution was used to assess the accuracy of the assumed coronary distribution of the model. The sensitivities and specificities of stress SPET for detection of CAD in individual coronary arteries and the classification regarding perceived number of diseased coronary arteries were also compared between the two coronary distributions (actual and assumed). The assumed coronary distribution corresponded to the actual coronary anatomy in all but one segment (#3). The majority of patients (80%) had 14 or more concordant segments. Sensitivities and specificities of stress SPET for detection of CAD in the coronary territories were similar, with the exception of the RCA territory, for which specificity for detection of CAD was better for the angiographically derived coronary artery distribution than for the model. There was 95% agreement between assumed and angiographically derived coronary distributions in classification to single- versus multi-vessel CAD. Reassignment of a single segment (segment #3) from the LCX to the LAD territory further improved the model's fit with the anatomic data. It is concluded that left ventricular segmentation using a model with assumed coronary artery distribution is valid for interpretation of SPET myocardial perfusion imaging.
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Circulación Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Modelos Cardiovasculares , Tomografía Computarizada de Emisión de Fotón Único , Función Ventricular Izquierda , Angiografía Coronaria , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Patient monitoring is a major indication for cardiac nuclear medicine procedures. Stress myocardial perfusion scintigraphy was initially used for diagnosis, but monitoring patients with coronary artery disease has become more common. Stress myocardial perfusion scintigraphy has been shown to provide a considerable amount of incremental prognostic information, which may be useful in selecting patients for therapy. In patients being considered for revascularization, fluorodeoxyglucose can be used to identify regions of dysfunctional but viable myocardium, even within regions that show fixed defects on stress perfusion imaging. It can be used to select a group of patients who will improve function with revascularization and who may have an improved outcome. Thus, cardiac nuclear medicine plays a pivotal role in monitoring patients with coronary artery disease.
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Enfermedad Coronaria/diagnóstico por imagen , Corazón/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Humanos , Radiofármacos , Tomografía Computarizada de Emisión , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
UNLABELLED: Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.