RESUMEN
OBJECTIVE: This study aims to record the overall perception of healthcare professionals on child abuse and identify potential affecting factors in a nationwide scale in Greece as well as to provide information that might be useful for future educational actions. MATERIALS AND METHODS: A total of 1,185 healthcare professionals in 60 hospitals with pediatric departments across Greece participated in this cross-sectional study. Participants included pediatricians, pediatric surgeons, residents, nurses, psychiatrists, psychologists, and social workers. Sections under investigation involved experience and training in child abuse, knowledge of formal and judicial issues, clinical knowledge, and self-assessment. RESULTS: Although more than half of the participants had confronted child abuse (n=712, 60.08%), only 273 (38.34% of them) submitted reports. One third of participants reported that they had received some training (n=440, 37.13%), mainly of postgraduate nature and based on personal initiative. Of those who reported child abuse, 175 (64.10%) had been trained. Each professional category was aware of topics regarding its own interest, without adequate knowledge of other disciplines. One third of psychiatrists, psychologists, and social workers felt confident in discussing with children and parents. Relevant scores were lower in the other categories. The lower scores were recorded among nurses and residents. The training deficit and reluctance to engage with judicial issues were the main causes of avoidance to deal with child abuse. CONCLUSIONS: Focused and organized training in child abuse is crucial to create reliable professionals in the field. The internet is a considerably helpful tool. Professionalism must characterize knowledge and practice in child abuse at the same level as in other medical topics. Motivation to engage should be early inspired and developed during the graduate years.
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Maltrato a los Niños , Niño , Humanos , Grecia , Estudios Transversales , Hospitales , Atención a la SaludRESUMEN
OBJECTIVE: The co-occurrence of coeliac disease (CD) and type 1 diabetes mellitus (T1DM) is well described and is mainly explained by sharing of common pathogenic mechanisms, such as common high-risk human lymphocyte antigen (HLA) genotypes (DR-DQ). PATIENTS AND METHODS: We describe a 12-year-old female patient with T1DM who presented with prolonged and severe glucose dysregulation. Extensive investigations, including coeliac screen, were negative. RESULTS: 3 years after glucose dysregulation manifested, coeliac screen testing was positive and coeliac disease was confirmed with bowel biopsy. Compliance to a gluten-free diet resulted in improvement of glucose control and seronegativity 9 months post-diagnosis. CONCLUSIONS: This is the first case report describing delayed seropositivity of CD and suggests that CD enteropathy may precede positive serology and could cause severe glucose dysregulation in patients with T1DM.
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Enfermedad Celíaca/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Autoanticuerpos/sangre , Glucemia/análisis , Enfermedad Celíaca/sangre , Enfermedad Celíaca/epidemiología , Niño , Comorbilidad , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Transglutaminasas/inmunologíaRESUMEN
OBJECTIVE: Eating disorders and obesity are serious, multifactorial diseases with increasing prevalence worldwide, often manifesting during childhood and adolescence. The aim of this study was to investigate the risk for developing eating disorders in children and adolescents of Primary and Secondary Education, with normal or excessive body weight. MATERIALS AND METHODS: A representative sample (N=3504) of students from schools of Western Greece, 50.2% boys, aged 10-16 years old, participated in the present cross-sectional epidemiological study. The students' dietary habits were assessed through multiple-choice questions and the risk for the development of eating disorders was evaluated using the Eating Attitudes Scale (EAT-13) validated questionnaire. Anthropometric measurements were obtained and the BMI, BMI% and BMI z-score were calculated. RESULTS: Nearly 20% of the participants, particularly those with overweight or obesity, were at increased risk for developing eating disorders (25% of normal weight-, 28.2% of overweight- and 33% of participants with obesity). Boys were more likely to develop eating disorders than girls, but not statistically significantly. A positive correlation of: (1) the overall EAT-13 score, (2) food pre-occupation score and (3) dieting score, with BMI z-score and obesity was found, as opposed to a negative correlation of Important Others score with BMI z-score and obesity. CONCLUSIONS: Increased awareness regarding the risk for developing eating disorders or disordered eating in children and adolescents with overweight and obesity is recommended to avoid underdiagnosis of this condition. Prompt identification of children at risk contributes to the implementation of targeted and effective prevention and treatment interventions.
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Conducta Alimentaria , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Obesidad Infantil/epidemiología , Adolescente , Niño , Estudios Transversales , Estudios Epidemiológicos , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Femenino , Grecia , Humanos , Masculino , Riesgo , Factores Sexuales , Encuestas y CuestionariosRESUMEN
OBJECTIVE: to estimate the incidence of reactive thrombocytosis among febrile young infants and to asses the utility of platelet count as a potential predictor of serious bacterial infection (SBI). DESIGN: retrospective study between January 2005 and December 2008. SETTING: tertiary care pediatric unit. PARTICIPANTS: all infants 29 to 89 days of age, admitted with rectal temperature > 38oC without a focus of infection. MAIN OUTCOME MEASURES: the results of the sepsis evaluation on admission were recorded. SBI included all cases of occult bacteremia, urinary tract infection, bacterial meningitis, pneumonia, bacterial gastroenteritis and infections of the soft tissues and bones. RESULTS: of the 408 infants studied, 103 (25.2%) had SBI. Platelet count was significantly higher in infants with SBI compared to those without (median 513000 /mm3 [interquartile range 455,000-598,000/mm3] vs median 398000/mm3; [interquartile range 313,000-463,000/mm3]; P<0.001). Thrombocytosis had only moderate ability in predicting SBI (area under the curve: 0.74, 95 % CI 0.70-0.79). The combination of platelet count >450,000/mm3, WBC >15,000/mm3, Creactive protein >2 mg/dL, and pyuria >10 WBC/hpf would lead to misclassification of 4 infants with SBI (3.9% of SBIs; negative likelihood ratio 0.08). CONCLUSION: reactive thrombocytosis was a frequent finding in young infants with SBI. Thrombocytosis >450,000 cells/mm3, in combination with leucocytosis, elevated CRP and pyuria, may help in early recognition of febrile young infants at risk for SBI.
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Infecciones Bacterianas/sangre , Trombocitosis/microbiología , Femenino , Fiebre/sangre , Fiebre/microbiología , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
AIM: The aims of this study were: 1) to perform brain single photon emission computed tomography (SPECT) in anesthetized rats with high resolution cameras (HRC) equipped with parallel hole collimation resolution of about 1 mm (HRC1) and 2 mm (HRC2); 2) to assess when and with which radio-tracer HRC1 SPECT shows advantages over HRC2. METHODS: We used two multicrystal HRCs with parallel square hole collimators, whose pure tungsten septa closely fit the crystals, in turn matched with a 4 inch2 position sensitive photomultiplier. HRC1 showed 1.1 mm and HCR2 2.1 mm resolution at collimator contact. HRCs performed 180 degrees semi-circular orbits around the head of rats: image reconstruction occurred with ordered subsets expectation maximization algorithms. Resolution of SPECT was measured with a Derenzo Phantom, resulting 1.4 mm for HRC1 and 2.3 mm for HRC2. Three rats were studied with [(99m)Tc]HMPAO, 3 rats with [(99m)Tc]bombesin (BN) and 48 h later with [(123)I]ioflupane (DaTSCAN). SPECT studies were reviewed by two experienced operators. RESULTS: Technetium-99m-HMPAO SPECT showed similar images with HRC1 and HRC2. The uptake of BN by amygdale, hippocampus and olfactory tract was detected by both cameras. DaTSCAN SPECT with HRC1 showed detailed image of the tail of the caudatus: this image was not obtained with HRC2. DaTSCAN and BN SPECT showed amygdale with both HRCs. However, only the central nucleus of amygdale takes up DaTSCAN, whereas central, lateral and basolateral amygdaloid nuclei express BN receptors. Only HRC1 SPECT showed amygdale larger with BN than with DaTSCAN. CONCLUSION: Spatial resolution of 1.4 mm is appropriate to detect selected subcerebral structures.
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Bombesina/análogos & derivados , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Nortropanos/farmacocinética , Compuestos de Organotecnecio/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único/veterinaria , Animales , Bombesina/farmacocinética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Diseño de Equipo , Análisis de Falla de Equipo , Aumento de la Imagen/instrumentación , Radiofármacos/farmacocinética , Ratas , Tomografía Computarizada de Emisión de Fotón Único/instrumentación , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
In the initial stages of tumor formation, overexpression of integrins identifying the RGD sequence (Arg-Gly-Asp) is observed. The aim of the present study was the synthesis and labeling of two novel RGD derivatives, via the precursor [99mTc(H2O)3(CO)3]+, as well as the radiochemical and radiopharmacological evaluation of the labeled products. The labeling led to the formation of a single product in each case (>98%), with noteworthy in vitro stability, fast blood clearance and elimination by the hepatobiliary and the urinary systems.
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Neoplasias/irrigación sanguínea , Neovascularización Patológica/diagnóstico por imagen , Oligopéptidos/síntesis química , Compuestos de Organotecnecio/síntesis química , Radiofármacos/síntesis química , Compuestos de Tecnecio/síntesis química , Animales , Femenino , Marcaje Isotópico/métodos , Ratones , Neovascularización Patológica/metabolismo , Oligopéptidos/química , Oligopéptidos/farmacocinética , Compuestos de Organotecnecio/química , Compuestos de Organotecnecio/farmacocinética , Cintigrafía , Radiofármacos/química , Radiofármacos/farmacocinética , Compuestos de Tecnecio/química , Distribución TisularRESUMEN
In human blood, breakdown of gastrin-releasing peptide and other bombesin-related peptides occurs in less than 15 min. This quick enzymatic cleavage might impair the diagnostic use of labelled bombesin (BN). 99mTc-labelled bombesin (99mTc BN1) was injected intravenously and dynamic uptake data were acquired for diagnosing 26 cancers of different origin: 15 breast, 3 prostate, 5 colo-rectal, 1 pancreas, 2 small cell lung cancers and 1 gastrinoma. Background subtracted tumour uptake data were plotted against time and fitted with known mathematical functions. Twenty-three out of 26 cancers showed rapid increase of radioactivity followed by a radioactivity plateau, with some oscillations around the average plateau value. The time to 80% of max activity (T80) was the reference parameter to measure and to compare the uptake speeds. The slowest T80 was 7 min in one T1b breast cancer, gastrinoma reached T80 in 5 min and node-positive prostate cancers in 2 min. N+ breast cancers showed T80 at 3.62 +/- 0.75 min, N- breast cancers at 5.5 +/- 0.88 min (p < 0.02). When all the tumours were considered, N+ tumours showed T80 at 2.68 +/- 1.03 min and N- cancers at 5.5 +/- 0.82 min. In all the cancer types, the uptake of 99mTc BN was faster than 10 min. This result shows the ability of 99mTc BN to image tumours. The faster uptake by N+ versus N- cancers probably depends on the higher blood flow in N+ cancers.
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Bombesina/análogos & derivados , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Compuestos de Organotecnecio , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Carcinoma de Células Pequeñas/irrigación sanguínea , Carcinoma de Células Pequeñas/diagnóstico por imagen , Carcinoma de Células Pequeñas/metabolismo , Neoplasias del Colon/irrigación sanguínea , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/metabolismo , Femenino , Gastrinoma/irrigación sanguínea , Gastrinoma/diagnóstico por imagen , Gastrinoma/metabolismo , Humanos , Cinética , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/metabolismo , Masculino , Estadificación de Neoplasias , Neoplasias/irrigación sanguínea , Neoplasias Pancreáticas/irrigación sanguínea , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/metabolismo , Neoplasias de la Próstata/irrigación sanguínea , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Cintigrafía , Radiofármacos , Receptores de Bombesina/metabolismo , Neoplasias del Recto/irrigación sanguínea , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/metabolismo , Flujo Sanguíneo RegionalRESUMEN
OBJECTIVE: Because the greater frequency of developmental dysplasia of the hip in the female could have an endocrine etiology, and because maternal smoking in pregnancy causes fetal endocrine disequilibrium, we investigated the anatomy of the hip in neonates of smoking and non-smoking mothers. METHODS: Clinical and sonographic examination was performed on 2066 hips of 521 male and 512 female neonates. In 48 male and 53 female neonates, the mothers smoked during pregnancy. RESULTS: The mean +/- SD alpha angle in the male neonates of the non-smoking mothers was 62.3 degrees +/- 5.1 degrees and of the smoking mothers 62.1 degrees +/- 4.9 degrees (p = 0.7). In the female neonates of the non-smoking and the smoking mothers, it was 60.7 degrees +/- 5.3 degrees and 61.9 degrees +/- 4.8 degrees, respectively (p = 0.02). The difference between the male and the female neonates of the non-smoking mothers was significant (p < 0.000001), but there was no significant difference between the female neonates of the smoking mothers and the male neonates (p = 0.5). Among the female neonates whose mothers were non-smokers, the number of those with hip type IIa or worse was significantly greater than among the female neonates whose mothers were smokers. The clinical findings were in agreement with the sonographic findings. CONCLUSIONS: Maternal smoking during pregnancy reduces the frequency of sonographic and possibly clinically detected hip dysplasia in female but not in male neonates. Nonetheless, because smoking causes numerous adverse effects on the fetus and child, it is contraindicated during pregnancy.
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Luxación Congénita de la Cadera/etiología , Efectos Tardíos de la Exposición Prenatal , Fumar/efectos adversos , Adolescente , Adulto , Femenino , Luxación Congénita de la Cadera/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos , UltrasonografíaRESUMEN
UNLABELLED: A pilot study has been carried out in order to verify the feasibility of scintigraphic driving for breast biopsy. A new high resolution (HR) gamma ray detector, the imaging probe (IP), and 99mTc [13Leu] Bombesin (99mTc BN), have been used to drive a mammotome biopsy needle after having fused radioisotope with digital X-ray images. IP is a mobile, high resolution, miniaturised gamma camera, whose field of view is one inch and whose spatial resolution is 2 mm. 99mTc BN is a new radiotracer derived from the well-known peptide, that has already shown very high sensitivity in detecting breast cancer. PATIENTS AND METHODS: Five patients very suspicious for breast cancer were studied. 185 MBq of 99mTc BN were i.v. injected and dynamic prone scintimammography was performed for 20 minutes with a conventional large field of view gamma camera. IP was matched with the biopsy system and digital X-ray device of a mammotome system, in order to fuse images and to use the mammotome pointer indifferently on X-ray, scintigraphic and fused images. Biopsy samples were counted and weighed: uptake was expressed as counts sec-1 gr-1. Samples were classified into high, intermediate and low uptake. Conventional histological assessment was blindly performed on the samples. RESULTS: All of the patients showed cancer. The T categorisation was T1a for two cancers and T1b for 3. Dynamic prone scintimammography with conventional gamma camera, as well as HR scintigraphy with IP showed spots of 99mTc BN uptake. Maximal mismatch between X-ray lesions and of hot spots imaged with IP before mammotome scintigraphy was 3.4 mm. All the high uptake samples and all but two of the intermediate uptake samples showed cancer, whereas histology found malignant tissue in only 2 out of the 8 low uptake samples. CONCLUSION: 99mTc BN confirms its high sensitivity in detecting breast cancer. IP is able to drive or co-drive breast biopsy when used with appropriate radiopharmaceuticals.
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Biopsia/métodos , Bombesina , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Compuestos de Organotecnecio , Radiofármacos , Tecnecio , Anciano , Bombesina/análogos & derivados , Femenino , Cámaras gamma , Humanos , Mamografía/métodos , Persona de Mediana Edad , Proyectos Piloto , CintigrafíaRESUMEN
BACKGROUND: Angiogenesis is the development of new blood vessels from pre-existing ones. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic activators. Our studies are focused on the detection of VEGF by use of radiolabeled anti-endothelial monoclonal antibodies, which have the ability to localize in newly-formed vasculature of a cancerous origin. MATERIALS AND METHODS: The anti-endothelial monoclonal antibody VG76e was labeled with Samarium-153 and Technetium-99m. Biodistribution of the radiolabeled species was assessed in normal female Swiss mice, while tumor uptake was also evaluated. RESULTS: VG76e was labeled with 99mTc and 153Sm, resulting in a single product with a labeling yield of over 95%. Biodistribution studies showed non-specific uptake in any organ, with elimination via the hepatobiliary system. Finally, satisfactory tumor uptake was observed for both radiolabeled derivatives. CONCLUSION: Monoclonal antibodies raised against epithelial growth factors or their receptors, when labeled with appropriate radionuclides, may be a useful tool for early tumor detection and eventually for therapy.
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Anticuerpos Monoclonales/farmacocinética , Neoplasias de la Mama/diagnóstico por imagen , Inmunoconjugados/farmacocinética , Neovascularización Patológica/diagnóstico por imagen , Radioisótopos/farmacocinética , Radiofármacos/farmacocinética , Samario/farmacocinética , Tecnecio/farmacocinética , Animales , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Inmunoconjugados/uso terapéutico , Marcaje Isotópico , Ratones , Ratones Desnudos , Neovascularización Patológica/metabolismo , Neovascularización Patológica/radioterapia , Radioisótopos/uso terapéutico , Cintigrafía , Radiofármacos/uso terapéutico , Samario/uso terapéutico , Tecnecio/uso terapéutico , Células Tumorales CultivadasRESUMEN
The results of studies conducted with a small field of view tomographic gamma camera based on a Position Sensitive Photomultiplier Tube are reported. The system has been used for the evaluation of radiopharmaceuticals in small animals. Phantom studies have shown a spatial resolution of 2mm in planar and 2-3mm in tomographic imaging. Imaging studies in mice have been carried out both in 2D and 3D. Conventional radiopharmaceuticals have been used and the results have been compared with images from a clinically used system.
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Bombesina/farmacocinética , Neoplasias Experimentales/diagnóstico por imagen , Radiofármacos/farmacocinética , Tecnecio/farmacocinética , Algoritmos , Animales , Cámaras gamma , Procesamiento de Imagen Asistido por Computador/instrumentación , Riñón/diagnóstico por imagen , Ratones , Ratones Desnudos , Cintigrafía , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador/instrumentación , Tecnecio/químicaRESUMEN
The labeling of a monoclonal (anti-CEA) and a polyclonal (IgG) antibody with 153Sm has been investigated, using the bicyclic anhydride of DTPA (cDTPAa) as the chelating agent. The radiochemical study was performed using a combination of radioanalytical techniques (gel filtration, HPLC, ITLC-SG and SDS-PAGE). Optimization of factors affecting labeling (pH, Ab, Ab-DTPA concentration, etc.) leads to a labeling yield higher than 90%. Biodistribution studies in normal mice showed slow blood clearance and high uptake into the liver, kidney and lungs.
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Anticuerpos Monoclonales/aislamiento & purificación , Inmunoconjugados/aislamiento & purificación , Ácido Pentético/análogos & derivados , Radioinmunoterapia , Radioisótopos/aislamiento & purificación , Samario/aislamiento & purificación , Animales , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Quelantes , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Femenino , Inmunoconjugados/farmacocinética , Inmunoconjugados/uso terapéutico , Ratones , Radioquímica , Radioisótopos/farmacocinética , Radioisótopos/uso terapéutico , Samario/farmacocinética , Samario/uso terapéutico , Distribución TisularRESUMEN
AIMS AND BACKGROUND: Bombesin-like neuropeptides work as neurotransmitters and growth factors at the same time. Several human cancers show overexpression of three receptors for mammalian counterparts of amphibia bombesins (ABNs), ie gastrin-releasing peptide (GRP), neuromedin B (NMB) and possibly another peptide. ABNs in turn are able to bind to mammalian and human receptors in vitro, and it is therefore interesting to study radioisotope-labeled bombesin (BN) and BN-like peptides as cancer seeking agents. METHODS AND STUDY DESIGN: Starting from the amino acid sequence of [Leu13] ABN, the Demokritos Institute has synthesized and labeled with technetium a new BN-like peptide that has the same biological characteristics as the amphibian peptide; changes were made only in the N-terminal part of the tetradecapeptide. After having obtained satisfactory results with 99mTc BN in a preclinical study, we started a phase I trial involving cancer patients as well as normal volunteers in Tomsk. Three normal volunteers, one patient with small cell lung cancer and one patient with primary prostate cancer were studied after iv injection of 185 MBq, corresponding to 0.7 micrograms of 99mTc BN. Dynamic images of the tumors were acquired for 20 mins, followed by SPET. Total body images were acquired in patients and normal volunteers 1 and 3 h after 99mTc BN acquisition. In addition, 99mTc sestamibi scintigraphy was performed in the patient with small cell lung carcinoma. RESULTS: No relevant side effects were observed. Both tumors were well visualized on early 1-2 mins images with planar as well as tomographic imaging. Total body images showed radioactivity in the liver, kidneys and thyroid gland. The stomach and spleen were ever imaged. Radioactivity was found in the urinary bladder 4 mins after injection in the patient with prostate cancer. Three-hour total body scans showed radioactivity in the duodenum. In the patient in whom also 99mTc sestamibi scintigraphy was performed, thyroid uptake was much higher with sestamibi than with 99mTc BN, whereas the uptake of small cell lung carcinoma was higher with 99mTc BN than with sestamibi. CONCLUSIONS: 99mTc BN is able to clearly image tumors with BN receptor overexpression. Our first impression is that in the future this radiopharmaceutical may serve as a cancer seeking agent and, due to its high tumoral uptake, also as a radiotracer for radioisotope-guided surgery.
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Bombesina/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Receptores de Bombesina/metabolismo , Compuestos de Tecnecio , Tomografía Computarizada de Emisión de Fotón Único/métodos , Carcinoma de Células Pequeñas/diagnóstico por imagen , Carcinoma de Células Pequeñas/metabolismo , Humanos , Leucina , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/metabolismo , Masculino , Neoplasias/cirugía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Radiofármacos , Tecnecio Tc 99m SestamibiRESUMEN
BACKGROUND: Several tumors including lung, prostate, ovarian, colon, and exocrine pancreatic cancer show receptors for the amphibian neurotransmitter and growth factor bombesin (BN) and its mammalian counterparts gastrin-releasing peptide and neuromedin B. Also breast cancer has been reported to show such receptors: the presence of BN receptors in primary breast cancer has been demonstrated on cultured cells and by autoradiography on breast tissue samples. Authors who have studied BN receptors in breast cancer do not agree on their frequency in primary cancer, but indicate that 100% of metastatic breast cancers show such receptors. METHODS: We examined three primary breast cancer patients with 99mTc BN and 99mTc sestamibi one week before surgery. One of them showed axillary node invasion. The same acquisition technique was used for breast and chest imaging with both radiopharmaceuticals, whereas total body images were acquired only with 99mTc BN. Also the administered radioactivity was different: 20 mCi of 99mTc sestamibi and 5-8 mCi of 99mTc BN. Dynamic images were acquired for 20 mins after iv injection with the patient in ventral decubitus and the gamma camera positioned in a lateral view, as is generally done in Khakhali's prone scintimammography. Anterior chest images were acquired for 30 mins. Prone scintimammography was performed one hour after administration of both tracers. ROIs were drawn on tumors and surrounding breast with the same technique in order to calculate the tumor to breast ratio (T/B). In addition, total body scan was performed one hour and three hours after 99mTc BN administration. All three patients underwent breast conserving surgery with lymphadenectomy. Postoperative pathologic assessment showed the following T and N stages in the three patients: T1bN0, T1c-N0, and T1cN1. RESULTS: All three cancers were imaged with both tracers. The T/B of 99mTc BN was always higher than that of 99mTc sestamibi. Chest uptake was always much higher with 99mTc sestamibi than with 99mTc BN. Comparison between 99mTc BN and 99mTc sestamibi images gave other intriguing results: in the N1 patient both tracers clearly imaged the invaded node, but on the 99mTc BM image the primary tumor was larger than on the 99mTc sestamibi image and the node was smaller. It is known that 99mTc BN is not taken up by vessels and inflammatory tissue. The time activity curves of the two tracers were significantly different in all patients, with an increase in 99mTc BN uptake in the first three to five minutes, followed by a less sharp uprise of the curve, quite similar to a plateau. CONCLUSIONS: Our first impression is that 99mTc BN is a useful breast cancer seeking agent and very promising for lymph node staging.
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Bombesina/metabolismo , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Receptores de Bombesina/metabolismo , Anciano , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cintigrafía , Radiofármacos , Compuestos de Tecnecio , Tecnecio Tc 99m Sestamibi , Regulación hacia ArribaRESUMEN
A new pentadecapeptide bombesin analogue was prepared by Fmoc synthesis, purified by HPLC and identified by electron ionization mass spectrometry. The biological activity of the new peptide was tested on isolated human colonic muscle cells and compared to native bombesin. Labelling of the new biomolecule with Tc-99m yielded a single radioactive species which remained stable at room temperature for eight hours. In a binding assay, the radiolabelled peptide showed high affinity for oat-cell carcinoma (Kd = 9.8 nM) and colorectal adenocarcinoma (Kd = 27.2 nM). Biodistribution studies, performed in normal rodents, indicated uptake by organs that normally express bombesin receptors, such as liver, intestines and kidneys. Scintigraphic studies, performed in nude mice transplanted with small cell lung carcinoma and colon cancer cells, showed significant tumor uptake two hours p.i. The new synthetic pentadecapeptide appears to have promise for several malignancies, including oat-cell lung carcinoma, colorectal cancer and gastroenteropancreatic (GEP) tumors.
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Bombesina , Carcinoma de Células Pequeñas/diagnóstico por imagen , Neoplasias del Colon/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Péptidos , Pertecnetato de Sodio Tc 99m , Animales , Bombesina/síntesis química , Bombesina/farmacocinética , Carcinoma de Células Pequeñas/metabolismo , Neoplasias del Colon/metabolismo , Femenino , Humanos , Marcaje Isotópico , Neoplasias Pulmonares/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Péptidos/síntesis química , Péptidos/farmacocinética , Cintigrafía , Ratas , Ratas Wistar , Receptores de Bombesina/metabolismo , Distribución Tisular , Células Tumorales CultivadasRESUMEN
Bombesin-like peptides are neurotransmitters and cancer growth factors. Several tumors, breast cancer among them, show one or more than one of the three known bombesin receptors. We have synthesized and labeled with technetium 99m a new pentadecapeptide, analogue to the leu13 amphibian bombesin (99mTc BN). Labeling yield was 83 +/- 4%. Prone Scintimammography was performed on five patients affected by breast cancers (T categorization: two T1b and three T1c), after injecting 0.7 mg, 185 to 296 MBq (5 to 8 mCi) of the peptide. Total body scan did not show free technetium biodistribution. No adverse reaction was observed. Prone Scintimammography with 99mTc Sestamibi (99mTc SM) was also performed few days later. 99mTc BN detected all 5 cancers, whereas 99mTc SM only four: all the T1c and one T1b cancer. Two of them showed axillary node invasion that was detected by both the radiotracers. A fibroadenoma present on contralateral breast to the one with cancer, was not detected neither by 99mTc SM nor by 99mTc BN. Tumor/breast normal tissue ratio (T/B) was constantly higher with 99mTc BN than with 99mTc SM. Maximal T/B was measured as 1.79 with 99mTc SM and 2.25 with 99mTc BN 5 min after fast i.v. administration. In conclusion our 99mTc BN is taken up by primary breast cancer showing higher T/B than 99mTc SM (p < 0.01). In our limited scale, 99mTc BN appears to be safe and, in our limited scale, even more accurate than 99mTc SM for detecting breast cancer.
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Bombesina/farmacocinética , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Péptidos/farmacocinética , Pertecnetato de Sodio Tc 99m/farmacocinética , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Femenino , Humanos , Ganglios Linfáticos/metabolismo , Metástasis Linfática , Persona de Mediana Edad , Cintigrafía , Tecnecio Tc 99m Sestamibi/farmacocinéticaRESUMEN
OBJECTIVE: To investigate whether maternal smoking during pregnancy causes retinal abnormalities in the newborn. STUDY DESIGN: One hundred sixty-two neonates of smoking mothers and 162 matched neonates of nonsmoking mothers (112 appropriate for gestational age [AGA], 30 small for gestational age [SGA], 20 large for gestational age [LGA] in each group) were studied. RESULTS: Retinal arterial narrowing and straightening (RANS) was observed in 52 and 10 eyes of the newborns of smoking and nonsmoking mothers, respectively (P <. 000001) in association with elevated blood pressure in the neonates. The frequency of RANS was more than 3-fold greater in the SGA neonates than in the AGA and LGA neonates of the smoking mothers. Retinal venous dilatation and tortuosity (RVDT) was found in 100 and 36 eyes of neonates of smoking and nonsmoking mothers, respectively (P <.000001). The frequency of RVDT in the SGA neonates of the smoking mothers was 2.5-fold and 4.2-fold greater than in the AGA infants and the LGA infants, respectively. Also, intraretinal hemorrhages were found in 61 and 31 eyes of neonates of smoking and nonsmoking mothers, respectively (P =.0007) in association with elevated hematocrit and RVDT, whereas no intraretinal hemorrhages were found when RANS was present. All retinal abnormalities resolved by 6 months in infants of smoking mothers and by 2 months in infants of nonsmoking mothers. CONCLUSIONS: Maternal smoking during pregnancy causes increased frequency of RANS, RVDT, and intraretinal hemorrhages; but these retinal abnormalities resolve by 6 months of age.
Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Vasos Retinianos/anomalías , Fumar/efectos adversos , Anomalías Congénitas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Masculino , Embarazo , Hemorragia Retiniana/epidemiología , Hemorragia Retiniana/etiologíaRESUMEN
Radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) are recent approaches in the diagnosis and treatment of cancer. They take advantage of the antibody specificity of tumor surface antigens and of the emitted radiation from suitable radioisotopes, as a means of imaging (RIS) or therapy (RIT). Research into RIS and RIT radiolabelled agents remains an ongoing process. Principles governing the choice of radionuclides, labelling protocols, antibody suitability, and optimization of "tumor to normal tissue ratios" are the same for both RIS and RIT. The investigational stages of the labelled product, prior to clinical application, are also the same. These stages include radiochemical and radiobiological evaluation as well as determination of immunoreactivity. Furthermore, RIS may be considered as the first stage in development, before progressing on to RIT. Differences between RIS and RIT are associated with the application of each technique, that is, the type of radiation emitted by the isotope, dosage regimens, haematopoetic toxicity and the appearance of human antimurine antibody response (HAMA). RIS has found widespread clinical application, detecting a variety of tumors. However, its potential lies in patient management and in detecting metastases. On the other hand RIT is still in its infancy. It appears promising, and for the moment is used as a complementary technique to surgery and/or chemotherapy in clinical trials on cancer treatment. Finally, incorporation of these basic principles arising from past experiences, into the design of RIT trials improve responses.
Asunto(s)
Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Radioinmunodetección , Radioinmunoterapia , Anticuerpos Monoclonales/efectos adversos , Humanos , Radioinmunodetección/efectos adversos , Radioinmunoterapia/efectos adversos , Radioisótopos/uso terapéutico , Dosificación RadioterapéuticaRESUMEN
OBJECTIVE: Leptin, a hormone that signals the amount of energy stores to the brain, has recently been shown to play a role in the regulation of several hypothalamic pituitary axes, including the growth hormone axis. To investigate a potential association between cord blood leptin concentrations and intrauterine growth we measured leptin concentrations in the cord blood of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) healthy newborns. PATIENTS AND MEASUREMENTS: Cord blood leptin concentrations were evaluated in 25 SGA, 100 AGA, and 45 LGA, neonates. RESULTS: Leptin was detectable in all newborns in concentrations comparable with those found in adults. Moreover, SGA newborns had lower leptin concentrations (3.70 +/- 1.81 micrograms/l) than AGA (5.65 +/- 4.98 micrograms/l) and LGA newborns (11.99 +/- 7.06 micrograms/ l)(P < 0.01). Cord blood leptin concentrations were significantly associated with ponderal index, cord blood insulin concentrations, placental weight and maternal serum leptin concentrations. Importantly, the association between cord blood leptin concentrations and intrauterine growth status persisted after adjusting for adiposity, placental weight, maternal serum leptin concentrations and cord blood insulin concentrations. CONCLUSIONS: Cord blood leptin concentrations are independently associated with intrauterine growth. Future studies are needed to elucidate the underlying mechanism and clarify the role of leptin in regulating growth and controlling appetite in newborns.
Asunto(s)
Desarrollo Embrionario y Fetal/fisiología , Sangre Fetal/química , Recién Nacido/sangre , Proteínas/análisis , Adulto , Femenino , Humanos , Recién Nacido Pequeño para la Edad Gestacional/sangre , Insulina/sangre , Leptina , Masculino , Tamaño de los Órganos , Placenta/anatomía & histología , Análisis de RegresiónRESUMEN
UNLABELLED: To investigate the toxic effect of tobacco smoke on the fetus, we measured in cord blood the concentrations of alpha-fetoprotein (AFP), the principal serum protein in early ontogenic development, and erythropoietin (EPO), as an index of chronic fetal hypoxia. A total of 103 consecutively enrolled term newborns of smoking mothers and 103 term infants of nonsmoking parents were studied. The mean +/- SD AFP concentrations in the newborns of the mothers who smoked 1-50, 5-50, and 10-50 cigarettes/day were 86.4 +/- 88.9, 96.3 +/- 91.9 and 118.7 +/- 103.7 ng/ml, respectively. The difference of all three groups from the control neonates (57.7 +/- 37.2) was significant. The EPO concentrations in the newborns of the mothers who smoked 1-50 (53.9 +/- 64.6 mU/ml) and 5-50 (56.3 +/- 68.5) cigarettes/day were significantly greater than in the control neonates (29.5 +/- 16.1). In the newborns of the smoking mothers there was a significant positive correlation between AFP concentrations and number of cigarettes smoked per day, and a negative correlation between AFP and birth weight or length. There was no correlation between AFP and EPO concentrations, as well as between EPO and birth weight, length or number of cigarettes smoked per day. CONCLUSION: The absence of a correlation between erythropoietin and birth weight or length and the negative correlations between alpha-fetoprotein and these anthropometric parameters suggest that the intra-uterine growth retardation caused by maternal smoking is not due to tissue hypoxia, but that both growth retardation and elevated alpha-fetoprotein result from the direct or indirect toxic effect of a factor(s) present in tobacco smoke.