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BACKGROUND: Anxiety and depression account for considerable cost to organizations, driven by both presenteeism (reduced performance due to attending work while ill) and absenteeism. Most research has focused on the impact of depression, with less attention given to anxiety and comorbid presentations. AIMS: To explore the cross-sectional relationship between depression and anxiety (individually and comorbidly) on workplace performance and sickness absence. METHODS: As part of a larger study to evaluate a mental health app, 4953 working Australians were recruited. Participants completed in-app assessment including demographic questions, the Patient Health Questionnaire-9, two-item Generalized Anxiety Disorder and questions from the World Health Organization Health and Work Performance Questionnaire. Cut-off scores were used to establish probable cases of depression alone, anxiety alone and comorbidity. RESULTS: Of the total sample, 7% met cut-off for depression only, 13% anxiety only, while 16% were comorbid. Those with comorbidity reported greater symptom severity, poorer work performance and more sickness absence compared to all other groups. Presenteeism and absenteeism were significantly worse in those with depression only and anxiety only compared to those with non-clinical symptom levels. Although those with depression alone tended to have poorer outcomes than the anxiety-only group, when sample prevalence rates were considered, the impact on presenteeism was comparable. CONCLUSIONS: Workplace functioning is heavily impacted by depression and anxiety both independently and where they co-occur. While comorbidity and more severe depression presentations stand out as impairing, workplace interventions should also prioritize targeting of anxiety disorders (and associated presenteeism) given their high population prevalence.
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Absentismo , Depresión , Ansiedad/epidemiología , Trastornos de Ansiedad/epidemiología , Australia/epidemiología , Comorbilidad , Depresión/epidemiología , Depresión/psicología , Humanos , Encuestas y Cuestionarios , Lugar de Trabajo/psicologíaRESUMEN
Clostridium difficile, the most common cause of hospital-associated diarrhoea in developed countries, presents major public health challenges. The high clinical and economic burden from C. difficile infection (CDI) relates to the high frequency of recurrent infections caused by either the same or different strains of C. difficile. An interval of 8 weeks after index infection is commonly used to classify recurrent CDI episodes. We assessed strains of C. difficile in a sample of patients with recurrent CDI in Western Australia from October 2011 to July 2017. The performance of different intervals between initial and subsequent episodes of CDI was investigated. Of 4612 patients with CDI, 1471 (32%) were identified with recurrence. PCR ribotyping data were available for initial and recurrent episodes for 551 patients. Relapse (recurrence with same ribotype (RT) as index episode) was found in 350 (64%) patients and reinfection (recurrence with new RT) in 201 (36%) patients. Our analysis indicates that 8- and 20-week intervals failed to adequately distinguish reinfection from relapse. In addition, living in a non-metropolitan area modified the effect of age on the risk of relapse. Where molecular epidemiological data are not available, we suggest that applying an 8-week interval to define recurrent CDI requires more consideration.
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Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Ribotipificación , Factores de Tiempo , Australia Occidental/epidemiología , Adulto JovenRESUMEN
Fathers are consistently underrepresented in parenting interventions and practitioners are an important target for change in interventions to enhance father engagement. This research examined the effects of two practitioner training programs in improving practitioner rated competencies and organizational father-inclusive practices. Two studies were conducted, each with a single group, repeated measures (pre, post and 2-month follow-up) design. Study 1 (N = 233) examined the outcomes of face-to-face training in improving practitioner ratings of competencies in engaging fathers, perceived effectiveness and use of father engagement strategies, organizational practices and rates of father engagement. Study 2 (N = 356) examined online training using the same outcome measures. Practitioners in both training formats improved in their competencies, organizational practices and rates of father engagement over time, yet those in the online format deteriorated in three competencies from post-training to follow-up. The implications for delivering practitioner training programs to enhance competencies and rates of father engagement are discussed.
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Educación , Padre , Responsabilidad Parental/psicología , Competencia Profesional , Adulto , Educación/métodos , Educación/normas , Padre/educación , Padre/psicología , Femenino , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Proyectos de InvestigaciónRESUMEN
A choice test bioassay was devised to screen compounds as potential semiochemicals (e.g., kairomones or allomones that mediate aggregation, attraction or repellence) for the obligate parasitic mite, Psoroptes ovis. The choice test used filter paper discs in a 1:4 test:control ratio and was found to be a reliable, effective and efficient method. Four mammalian lipid components were assessed as potential attractants-linoleic acid, arachidonic acid, methyl myristate and squalene-, and the insect/tick repellent DEET for potential repellence. Linoleic acid was significantly attractive to P. ovis adult females and has the potential to act as an attractant. Identification of P. ovis semiochemicals, especially attractants, would be beneficial in the development of novel control methods and tools for this species. This is essential considering the increase in resistance to the limited prophylactic chemical treatments in the UK, and the high prevalence of scab infections.
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Quimiotaxis , Lípidos/análisis , Infestaciones por Ácaros/veterinaria , Sustancias Protectoras/análisis , Psoroptidae/fisiología , Enfermedades de las Ovejas/prevención & control , Control de Ácaros y Garrapatas/métodos , Animales , Femenino , Infestaciones por Ácaros/prevención & control , OvinosRESUMEN
Evidence-based parenting interventions have been developed and evaluated largely with mothers. This study examined practitioner reports of rates of father attendance, barriers to engagement, organizational support for father-inclusive practice, participation in training in father engagement, and competencies in working with fathers. It also explored predictors of practitioner competence and rates of father attendance. Practitioners (N = 210) who delivered parenting interventions completed an online survey. Participants reported high levels of confidence in engaging fathers, but only one in three had participated in training and levels of father attendance in parenting interventions were low. Logistic regressions showed that high levels of practitioner competence were predicted by participation in training. Moderate levels of father attendance (vs. low levels) were predicted by greater number of years of experience while high levels of attendance (vs. low levels) were predicted by greater experience, higher levels of competence and higher levels of organizational support. The implications of the findings to informing policy and practice for enhancing father engagement are discussed.
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Relaciones Padre-Hijo , Padre/psicología , Responsabilidad Parental/psicología , Competencia Profesional , Psicología/normas , Trabajadores Sociales , Encuestas y Cuestionarios , Femenino , Humanos , Modelos Logísticos , Masculino , Trabajadores Sociales/psicologíaRESUMEN
Little is known about Clostridium difficile infection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage of C. difficile among the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n = 76) and healthy community members (n = 138), C. difficile antigen and toxins were tested by enzyme immunoassay. Stool samples were subsequently analyzed by culture and molecular detection of toxin genes, and PCR ribotyping of isolates. To examine awareness among hospital staff and students, participants were asked to complete a self-administered questionnaire. For the hospital and community studies, the prevalence of non-toxigenic C. difficile colonization was 16% and 2%, respectively. The prevalence of CDI among hospital inpatients with diarrhea was 13%. Out of 22 C. difficile strains from hospital inpatients, the toxigenic ribotypes 043 and 017 were most common (both 14%). In univariate analysis, C. difficile colonization in hospital inpatients was significantly associated with greater duration of hospitalization and use of penicillin (both P < 0·05). Absence of these factors was a possible reason for low colonization in the community. Only 3% of 154 respondents answered all questions correctly in the awareness survey. C. difficile colonization is prevalent in a Malaysian hospital setting but not in the elderly community with little or no contact with hospitals. Awareness of CDI is alarmingly poor.
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Portador Sano/epidemiología , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/epidemiología , Infección Hospitalaria/epidemiología , Epidemiología Molecular , Adulto , Anciano , Anciano de 80 o más Años , Portador Sano/microbiología , Infecciones por Clostridium/complicaciones , Infecciones por Clostridium/microbiología , Infección Hospitalaria/microbiología , Diarrea/epidemiología , Diarrea/etiología , Diarrea/microbiología , Heces/microbiología , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Ribotipificación , Factores de Riesgo , Centros de Atención Terciaria , Adulto JovenRESUMEN
Coiled planar capillary chromatography columns (0.9 mm I.D. × 60 cm L) were 3D printed in stainless steel (316L), and titanium (Ti-6Al-4V) alloys (external dimensions of ~5 × 30 × 58 mm), and either slurry packed with various sized reversed-phase octadecylsilica particles, or filled with an in situ prepared methacrylate based monolith. Coiled printed columns were coupled directly with 30 × 30 mm Peltier thermoelectric direct contact heater/cooler modules. Preliminary results show the potential of using such 3D printed columns in future portable chromatographic devices.
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A thorough review of the literature has identified the key factors and interactions that affect the growth of mite pests on stored grain commodities. Although many factors influence mite growth, the change and combinations of the physical conditions (temperature, relative humidity and/or moisture content) during the storage period are likely to have the greatest impact, with biological factors (e.g. predators and commodity) playing an important role. There is limited information on the effects of climate change, light, species interactions, local density dependant factors, spread of mycotoxins and action thresholds for mites. A greater understanding of these factors may identify alternative control techniques. The ability to predict mite population dynamics over a range of environmental conditions, both physical and biological, is essential in providing an early warning of mite infestations, advising when appropriate control measures are required and for evaluating control measures. This information may provide a useful aid in predicting and preventing mite population development as part of a risk based decision support system.
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Acaridae/crecimiento & desarrollo , Acaricidas , Acaridae/fisiología , Animales , Conducta Animal , Clima , Femenino , Humedad , Masculino , Control Biológico de Vectores , TemperaturaRESUMEN
BACKGROUND: Little is known about Clostridioides difficile infection (CDI) in patients with cystic fibrosis (CF). The aim of this study was to investigate the prevalence, molecular epidemiology and risk factors for CDI in asymptomatic and symptomatic adults with CF in Western Australia. METHODS: Faecal samples from symptomatic and asymptomatic patients were prospectively collected and tested for the presence of C. difficile by toxigenic culture. Ribotyping was performed by established protocols. Logistic regression analysis was performed to analyse the risk factors for C. difficile colonization and infection. Extensive environmental sampling was performed within the CF clinic in Perth. RESULTS: The prevalence rates of asymptomatic toxigenic and non-toxigenic C. difficile colonization were 30% (14/46 patients) and 24% (11/46 patients), respectively. Fifteen ribotypes (RTs) of C. difficile were identified, of which non-toxigenic RT 039 was the most common. Among the symptomatic patients, the prevalence of toxigenic CDI was 33% (11/33 patients). Impaired glucose tolerance/diabetes mellitus and duration of intravenous antibiotic use in the past 12 months were significantly associated with increased risk of asymptomatic toxigenic C. difficile carriage and CDI. A trend towards higher CF transmembrane conductance regulator modulator treatment was observed in the CDI group. Extensive environmental sampling showed no evidence of toxigenic C. difficile contamination within the CF clinic. CONCLUSIONS: A high prevalence of asymptomatic carriage of toxigenic C. difficile was observed in adults with CF, comparable with that observed in the symptomatic CF population. There was no evidence of direct person-to-person transmission.
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Clostridioides difficile , Infecciones por Clostridium , Fibrosis Quística , Adulto , Australia/epidemiología , Clostridioides , Clostridioides difficile/genética , Infecciones por Clostridium/epidemiología , Fibrosis Quística/complicaciones , Fibrosis Quística/epidemiología , HumanosRESUMEN
Clostridium difficile has not been studied in detail in Asia, particularly Southeast Asia. We thus performed a prevalence study across four hospitals in Central Java province, Indonesia. Stool samples were collected from patients with diarrhoea and tested by enzyme immunoassay for glutamate dehydrogenase (GDH) and toxin A/B (C DIFF QUIK CHEK COMPLETE, TechLab). Specimens were cultured and molecular typing was performed. In total, 340 samples were tested, of which 70 (20.6%) were GDH positive, with toxin detected in 19 (5.6%). Toxigenic C. difficile was isolated from 37 specimens (10.9%), while a further 36 (10.6%) nontoxigenic isolates were identified. The most common strain was ribotype 017 (24.3% of 74 isolates), followed by nontoxigenic types QX 224 (9.5%), and QX 238 and QX 108 (both 8.1%). The high prevalence of C. difficile highlights a need for ongoing surveillance of C. difficile infection in Indonesia.
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The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole).
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Acaricidas/farmacología , Evaluación Preclínica de Medicamentos/veterinaria , Infestaciones por Ácaros/veterinaria , Psoroptidae/efectos de los fármacos , Enfermedades de las Ovejas/prevención & control , Acaricidas/normas , Animales , Infestaciones por Ácaros/prevención & control , OvinosRESUMEN
Osteoclastic differentiation is induced from hematopoietic cells in the presence of 1,25-(OH)2D3 by stromal cells that are present in bone but not in hematopoietic spleen. Recent evidence suggests that prostaglandins (PGs) are essential for this process. In this communication we describe experiments in which we have examined further the role of PGE2 in osteoclast formation. We found a marked reduction in basal, 1,25-(OH)2D3, and IL-3-induced production of calcitonin receptor (CTR)-positive cells and bone resorption by cyclooxygenase inhibitors, which was restored by PGE2 addition. Although some stromal cell types (ST2 cells) that support osteoclast formation from spleen cells produced PGs in response to 1,25-(OH)2D3, others (ts8 and calvarial cells) did not, either alone or in combination with spleen cells. On the other hand, both bone marrow and spleen cells produced amounts of PGE2 in response to 1,25-(OH)2D3 that were sufficient to account for osteoclast formation. Osteoclast-inductive ts8 cells were able to support osteoclast formation from spleen cells in the presence of 1,25-(OH)2D3 or PGE2 even if devitalized. Incubation of ts8 cells in these agents before devitalization did not avoid the requirement for the presence of PGE2 or 1,25-(OH)2D3 during subsequent incubation with spleen cells. Thus, hematopoietic cells produce sufficient PGE2 for osteoclast formation, and the PGE2 thus produced acts on hematopoietic precursors, which can be induced in the presence of PGE2 to express CTR and resorb bone on contact with osteoclast-inductive stromal cells. The ability of osteoclast-inductive cells to support osteoclast formation appears not to rest on their ability to produce, induce, or respond to PGE2.
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Desarrollo Óseo/efectos de los fármacos , Dinoprostona/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Animales , Autorradiografía , Células de la Médula Ósea , Células Cultivadas , Dinoprostona/análisis , Radioisótopos de Yodo , Ratones , Ratones Endogámicos CBA , Cráneo/citologíaRESUMEN
Prostaglandins (PG) act as direct inhibitors of mature osteoclasts, but although resorption-inhibition is also observed initially PG increase bone resorption in organ culture. This suggests that PG influence bone resorption in organ culture through actions on cell types other than mature osteoclasts. We have therefore tested the effects of PG E1, E2, and F2 alpha on the differentiation of osteoclastic phenotype in mouse bone marrow cultures using bone resorption and calcitonin receptors (CTR) as markers of osteoclastic differentiation. We found that PGE2 (10(-6)-10(-9) M) and PGE1 (10(-6)-10(-7) M) induced a significant increase in CTR-positive cell numbers, to levels five to eight times those seen in controls and similar to the number induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Bone resorption was increased (10(-7) M PGE2 and 10(-6) M PGE1) in association with the increased CTR-positive cell numbers, suggesting that the PG also induced resorptive function. 1,25-(OH)2D3 increased both the number of CTR-positive cells and the extent of resorption per cell; the additional presence of PG did not affect the number of CTR-positive cells but did reduce bone resorption compared with 1,25-(OH)2D3 alone. PGF2 alpha had no significant effect on CTR-positive cell induction or bone resorption. The results suggest that PGE1 and E2 induce osteoclastic differentiation in mouse bone marrow cultures and inhibit the function of the osteoclasts thus formed.(ABSTRACT TRUNCATED AT 250 WORDS)
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Alprostadil/fisiología , Células de la Médula Ósea , Dinoprost/fisiología , Dinoprostona/fisiología , Osteoclastos/citología , Animales , Autorradiografía , Resorción Ósea/fisiopatología , Calcitonina/metabolismo , Diferenciación Celular/fisiología , Células Cultivadas , Radioisótopos de Yodo , Ratones , Ratones Endogámicos CBA , Receptores de Calcitonina , Receptores de Superficie Celular/análisisRESUMEN
The osteoclast is known to be derived from the hematopoietic stem cell, but its lineage remains controversial. There is evidence that osteoclastic differentiation is induced through a contact-dependent interaction between bone marrow stromal cells and hematopoietic precursors. To analyze osteoclastic lineage, colonies were generated in semisolid medium from mouse spleen cells in the presence of Wehi-conditioned medium, interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage colony-stimulating factor (M-CSF) with or without erythropoietin (epo). After 5-8 days colonies were picked and phenotyped and incubated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on bone slices or coverslips with bone marrow-derived cell lines (ts8 or ST2) that induce osteoclastic differentiation. Cells of osteoclastic phenotype [as judged by calcitonin receptor (CTR) expression or bone resorption] were observed only in multilineage colonies. The ability of cells that generate macrophage colonies (CFU-M) to generate osteoclasts was tested by incubating alveolar or peritoneal macrophages on ts8 or ST2 cells. Despite colony formation, no osteoclastic differentiation was detectable. Last, individual cells from blast cell colonies were incubated (1 cell per culture well) on ts8 or ST2 cells in the presence of 1,25-(OH)2D3 and epo (to expose the lineage potential of the plated cell). We found CTR-positive (CTRP) cells in 6 of 66 macrophage colonies, 7 of 12 granulocyte-macrophage (GM) colonies, and 49 of 50 colonies containing multiple lineages other than GM colonies. No single-lineage CTRP colonies were observed. Although most macrophage colonies did not contain CTRP, no CTRP were observed in colonies from which macrophages were absent. These results suggest that osteoclasts are derived from a multilineage precursor rather than from CFU-M.
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Factor Estimulante de Colonias de Granulocitos y Macrófagos/fisiología , Células Madre Hematopoyéticas/citología , Factor Estimulante de Colonias de Macrófagos/fisiología , Osteoclastos/citología , Animales , Células Cultivadas , Medios de Cultivo , Macrófagos Alveolares/citología , Ratones , Ratones Endogámicos , Fenotipo , Bazo/citología , Células Madre/citologíaRESUMEN
The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up (p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up (p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.
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Dorso/fisiología , Músculo Esquelético/fisiología , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/prevención & control , Levantamiento de Peso/fisiología , Anciano , Análisis de Varianza , Densidad Ósea/fisiología , Distribución de Chi-Cuadrado , Ejercicio Físico/fisiología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Fracturas de la Columna Vertebral/diagnóstico por imagenRESUMEN
UNLABELLED: Rapidly dividing cells up-regulate the number of transcobalamin II receptors during DNA replication. We have developed diethylene-triaminepentaacetate (DTPA) cobalamin analogs for the purpose of imaging transcobalamin II receptors in malignant and nonmalignant tissue. METHODS: Methyl-, adenosyl- and cyanocobalamin-b-(4-aminobutyl)-amide-DTPA analogs were synthesized. In vitro binding of the analogs to the transcobalamin proteins was assessed by the unsaturated vitamin B12 binding capacity assay and compared to DTPA and cyanocobalamin. The biodistribution of the 111In-DTPA cobalamin analogs was measured at 24 hr after injection into sarcoma-bearing mice and non-tumor-bearing mice and pigs. RESULTS: Methyl-, adenosyl- and cyanocobalamin-b-(4-aminobutyl)-amide-DTPA analogs and DTPA were 94.0%, 90.4%, 66.4%, and 3.6%, respectively, as efficient in binding to the transcobalamin proteins when compared to cyanocobalamin. At 24 hr after administration, the cobalamin analogs had 5-17 times and 20-29 times, respectively, the amount of uptake within the resected tissue samples and transplanted sarcomas when compared to 111In-DTPA. CONCLUSION: The radiolabeled DTPA cobalamin analogs are biologically active. Preliminary animal studies suggest that the analogs could be effective in vivo transcobalamin II receptor imaging agents.
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Radioisótopos de Indio , Ácido Pentético , Receptores de Superficie Celular/análisis , Tecnecio , Transcobalaminas/análisis , Vitamina B 12 , Animales , Cobamidas , Femenino , Marcaje Isotópico , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Cintigrafía , Sarcoma Experimental/diagnóstico por imagen , Porcinos , Distribución Tisular , Transcobalaminas/metabolismo , Vitamina B 12/análogos & derivadosRESUMEN
Lymphoscintigraphy is a useful technique for the evaluation of lymphatic function in the presence of limb swelling. The authors report a case where proximal lower limb and genital swelling in a 23-yr-old man was investigated by lymphoscintigraphy. The patient had a history of previous surgery and subsequent infection in the affected groin. Lower limb lymphoscintigraphy showed features of an unusual lymphatic drainage pattern that most likely represented adaptation to chronic lymphatic insufficiency. The drainage pattern was characterized by marked dermal backflow pattern, aberrant lymph node uptake in the abdomen and chest and unexpected avid radiotracer uptake in the axillae bilaterally.
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Axila/diagnóstico por imagen , Pierna/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Linfocintigrafia , Adulto , Ingle/diagnóstico por imagen , Humanos , Linfedema/diagnóstico por imagen , Linfedema/etiología , MasculinoRESUMEN
Vitamin B12 is essential for life. Lack of it results in pernicious anemia and death. Conversely, the demand for vitamin B12 increases in rapidly dividing tumors. This is secondary to the direct involvement of vitamin B12 in mitochondrial metabolism as well as its indirect role in the production of thymidylate and S-adenosylmethionine. The latter 2 substances are needed for DNA synthesis and cellular methylation reactions, respectively. Novel radiolabeling of adenosylcobalamin has proven to be useful in the imaging of transplanted and spontaneous tumors in animals. Herein, we describe what we believe to be the first human to have imaging with conventional gamma cameras of vitamin B12 metabolism in a breast tumor.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/metabolismo , Cobamidas/metabolismo , Radioisótopos de Indio , Recurrencia Local de Neoplasia/metabolismo , Ácido Pentético , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , CintigrafíaRESUMEN
OBJECTIVE: To study the biodistribution of a vitamin B12 analog, indium In 111-labeled diethylenetriaminepentaacetate adenosylcobalamin (In 111 DAC), in patients recently diagnosed as having primary or recurrent malignancy. PATIENTS AND METHODS: Thirty patients (14 women and 16 men) with radiographically or clinically diagnosed breast, lung, colon, sarcomatous, thyroid, or central nervous system malignancies were studied prior to definitive surgery or biopsy. A maximum of 650 microCi (2.2 microg) of In 111 DAC was administered intravenously. Vitamin B12 and folate levels were determined prior to injection. Serum clearance and urinary and stool excretion of the tracer were measured. Images were routinely obtained at 0.5, 3 to 5, and 20 to 24 hours after injection. Biodistribution of In 111 DAC was determined by computer analysis of regions of interest. RESULTS: Serum T1/2 clearance was 7 minutes. Average urinary and stool excretion of the injected dose over 24 hours was 26.1% and 0.4%, respectively. The greatest focal uptake of In 111 DAC occurred in the liver and spleen, followed by the nasal cavity and salivary and lacrimal glands. The average tumor uptake of the injected dose was 2% at 30 minutes and 1.5% at 24 hours. High-grade primary and metastatic breast, lung, colon, thyroid, and sarcomatous malignancies were all imaged at 3 to 5 hours after injection. Central nervous system tumors and advanced metastatic prostate cancer were best identified at 24 hours. Mammographically occult, palpable, and nonpalpable breast cancers were delineated by In 111 DAC. Low-grade malignancies as well as early skeletal metastatic disease were not effectively imaged by the vitamin B12 tracer. Patients with elevated baseline vitamin B12 or those concurrently taking corticosteroids appeared to have optimal visualization of their malignancies. CONCLUSION: Vitamin B12 may be a useful vehicle for delivering diagnostic and therapeutic agents to various malignancies. Further evaluation of cobalamin analogs and their interaction with transport proteins and cellular receptors within malignant tissue and infection is warranted.
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Cobamidas/metabolismo , Radioisótopos de Indio/metabolismo , Neoplasias/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias del Sistema Nervioso Central/metabolismo , Cobamidas/administración & dosificación , Cobamidas/sangre , Cobamidas/orina , Neoplasias del Colon/metabolismo , Femenino , Humanos , Radioisótopos de Indio/administración & dosificación , Radioisótopos de Indio/sangre , Radioisótopos de Indio/orina , Infusiones Intravenosas , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/orina , Neoplasias de la Próstata/metabolismo , Sarcoma/metabolismo , Neoplasias de la Tiroides/metabolismo , Distribución TisularRESUMEN
Three vitamin B12 (cyanocobalamin) conjugates bearing one nido-carborane molecule or two nido-carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-amidobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as 11B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carborane conjugates was assessed by the unsaturated vitamin B12 binding capacity assay. When compared with 57Co cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carborane, and cyanocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy.