RESUMEN
Whole bladder magnetic resonance image-guided radiotherapy using the 1.5 Telsa MR-linac is feasible. Full online adaptive planning workflow based on the anatomy seen at each fraction was performed. This was delivered within 45 min. Intra-fraction bladder filling did not compromise target coverage. Patients reported acceptable tolerance of treatment.
RESUMEN
BACKGROUND: Penis cancer is rare and clinical trial evidence on which to base treatment decisions is limited. Case reports suggest that the combination of docetaxel, cisplatin and 5-flurouracil (TPF) is highly active in this disease. METHODS: Twenty-nine patients with locally advanced or metastatic squamous carcinoma of the penis were recruited into a single-arm phase II trial from nine UK centres. Up to three cycles of chemotherapy were received (docetaxel 75 mg m(-2) day 1, cisplatin 60 mg m(-2) day 1, 5-flurouracil 750 mg m(-2) per day days 1-5, repeated every 3 weeks). Primary outcome was objective response (assessed by RECIST). Fourteen or more responses in 26 evaluable patients were required to confirm a response rate of 60% or higher (Fleming-A'Hern design), warranting further evaluation. Secondary endpoints included toxicity and survival. RESULTS: 10/26 evaluable patients (38.5%, 95% CI: 20.2-59.4) achieved an objective response. Two patients with locally advanced disease achieved radiological complete remission. 65.5% of patients experienced at least one grade 3/4 adverse event. CONCLUSION: Docetaxel, cisplatin and 5FU did not reach the pre-determined threshold for further research and caused significant toxicity. Our results do not support the routine use of TPF. The observed complete responses support further investigation of combination chemotherapy in the neoadjuvant setting.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Fluorouracilo/administración & dosificación , Neoplasias del Pene/tratamiento farmacológico , Taxoides/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cisplatino/efectos adversos , Progresión de la Enfermedad , Docetaxel , Fluorouracilo/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias del Pene/mortalidad , Neoplasias del Pene/patología , Análisis de Supervivencia , Taxoides/efectos adversos , Reino Unido/epidemiologíaRESUMEN
Trypanosoma cruzi and Trypanosoma rangeli are human-infective blood parasites, largely restricted to Central and South America. They also infect a wide range of wild and domestic mammals and are transmitted by a numerous species of triatomine bugs. There are significant overlaps in the host and geographical ranges of both species. The two species consist of a number of distinct phylogenetic lineages. A range of PCR-based techniques have been developed to differentiate between these species and to assign their isolates into lineages. However, the existence of at least six and five lineages within T. cruzi and T. rangeli, respectively, makes identification of the full range of isolates difficult and time consuming. Here we have applied fluorescent fragment length barcoding (FFLB) to the problem of identifying and genotyping T. cruzi, T. rangeli and other South American trypanosomes. This technique discriminates species on the basis of length polymorphism of regions of the rDNA locus. FFLB was able to differentiate many trypanosome species known from South American mammals: T. cruzi cruzi, T. cruzi marinkellei, T. dionisii-like, T. evansi, T. lewisi, T. rangeli, T. theileri and T. vivax. Furthermore, all five T. rangeli lineages and many T. cruzi lineages could be identified, except the hybrid lineages TcV and TcVI that could not be distinguished from lineages III and II respectively. This method also allowed identification of mixed infections of T. cruzi and T. rangeli lineages in naturally infected triatomine bugs. The ability of FFLB to genotype multiple lineages of T. cruzi and T. rangeli together with other trypanosome species, using the same primer sets is an advantage over other currently available techniques. Overall, these results demonstrate that FFLB is a useful method for species diagnosis, genotyping and understanding the epidemiology of American trypanosomes.
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Trypanosoma/genética , Animales , Genotipo , Reacción en Cadena de la Polimerasa , América del Sur , Especificidad de la EspecieRESUMEN
Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39-73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2-5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer.
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Antineoplásicos/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Neoplasias/tratamiento farmacológico , Purinas/administración & dosificación , Administración Oral , Adulto , Anciano , Antineoplásicos/efectos adversos , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Inhibidores Enzimáticos/efectos adversos , Femenino , Humanos , Hiperglucemia/inducido químicamente , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Purinas/efectos adversos , Roscovitina , Resultado del TratamientoRESUMEN
A description has been given of those particular microanatomical features of the epidermis which are responsible for its mechanical stability--in particular half desmosomes, the desmosome tonofilament complex and interlocking squames. The functions of these structures have been illustrated by experiments which expose the skin to suction, friction and enzymatic digestion.
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Epidermis/lesiones , Vesícula/patología , Epidermis/enzimología , Epidermis/patología , Epidermis/ultraestructura , Humanos , Péptido Hidrolasas/metabolismoRESUMEN
A brief review of recent Nicaraguan political history and its impact on health care is presented. Interviews with midwives, nurses, and physicians are reported to illustrate the current health situation in Nicaragua. The effects of structural adjustment and foreign debt repayment on health in Nicaragua are discussed.
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Atención a la Salud/organización & administración , Partería , Política , Niño , Servicios de Salud del Niño/organización & administración , Atención a la Salud/economía , Países en Desarrollo , Femenino , Humanos , Servicios de Salud Materna/organización & administración , Nicaragua , EmbarazoAsunto(s)
Laboratorios/organización & administración , Canadá , Análisis Costo-Beneficio , Toma de Decisiones en la Organización , Laboratorios/economía , Laboratorios/tendencias , Liderazgo , Modelos Organizacionales , Programas Nacionales de Salud/economía , Programas Nacionales de Salud/organización & administración , Evaluación de Resultado en la Atención de Salud , Sector Privado , Sector Público , Calidad de la Atención de SaludRESUMEN
The open channel diameter of Escherichia coli recombinant large-conductance mechanosensitive ion channels (MscL) was estimated using the model of Hille (Hille, B. 1968. Pharmacological modifications of the sodium channels of frog nerve. J. Gen. Physiol. 51:199-219) that relates the pore size to conductance. Based on the MscL conductance of 3.8 nS, and assumed pore lengths, a channel diameter of 34 to 46 A was calculated. To estimate the pore size experimentally, the effect of large organic ions on the conductance of MscL was examined. Poly-L-lysines (PLLs) with a diameter of 37 A or larger significantly reduced channel conductance, whereas spermine (approximately 15 A), PLL19 (approximately 25 A) and 1,1'-bis-(3-(1'-methyl-(4,4'-bipyridinium)-1-yl)-propyl)-4,4'-b ipyridinium (approximately 30 A) had no effect. The smaller organic ions putrescine, cadaverine, spermine, and succinate all permeated the channel. We conclude that the open pore diameter of the MscL is approximately 40 A, indicating that the MscL has one of the largest channel pores yet described. This channel diameter is consistent with the proposed homohexameric model of the MscL.
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Escherichia coli/metabolismo , Canales Iónicos/química , Canales Iónicos/metabolismo , Proteínas Bacterianas , Fenómenos Biofísicos , Biofisica , Conductividad Eléctrica , Activación del Canal Iónico , Modelos Químicos , Permeabilidad , Poliaminas/metabolismo , Estrés MecánicoRESUMEN
The performance of 47 patients with Parkinson's disease on a battery of tests of cognition, motor function, disability and mood was compared with the performance of 47 healthy control subjects who were matched to the patients on the basis of age, sex and pre-morbid IQ. An increased prevalence of impairment over a range of cognitive functions was observed in the Parkinson's disease patients as compared with their matched controls. The differences between the Parkinson's disease patients and controls could not be accounted for by factors such as depressed mood, effects of medication or motor impairment. Our findings are discussed in relation to the methodology of previous studies in this area and to the need for a comprehensive clinico-pathological longitudinal study.
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Trastornos del Conocimiento/diagnóstico , Demencia/diagnóstico , Pruebas Neuropsicológicas , Enfermedad de Parkinson/diagnóstico , Actividades Cotidianas/psicología , Síntomas Afectivos/diagnóstico , Síntomas Afectivos/psicología , Anciano , Trastornos del Conocimiento/psicología , Estudios de Cohortes , Demencia/psicología , Femenino , Humanos , Inteligencia , Masculino , Persona de Mediana Edad , Examen Neurológico , Enfermedad de Parkinson/psicología , Escalas de WechslerRESUMEN
In a comparison of assessment methods of severity of depressive illness, the Montgomery-Asberg Scale had, broadly, a performance equal to the Hamilton Scale. The Beck Depression Inventory, it subscale, and the Wakefield Inventory all had overall poor performances and should now be abandoned in research. The two-patient-rated scales were, overall, similar and fairly satisfactory measures. The comparisons were at points in severity of illness and not on change of severity.
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Trastorno Depresivo/diagnóstico , Escalas de Valoración Psiquiátrica , Adulto , Anciano , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Asma/terapia , Urgencias Médicas , Adulto , Servicio de Urgencia en Hospital , Femenino , HumanosRESUMEN
Dispersed cell cultures of guinea-pig epidermis have been maintained for up to 36 days. The progress of these cultures has been studied by phase contrast microscopy, the adenosine triphosphatase reaction, and cinephotomicrography. Langerhans cells have been identified and their behaviour studied, particularly in relation to keratinocytes.
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Células de Langerhans/citología , Piel/citología , Adenosina Trifosfatasas , Animales , Técnicas de Cultivo , Cobayas , Queratinas , Células de Langerhans/enzimología , Melanocitos , Microscopía de Contraste de Fase , FotomicrografíaRESUMEN
Rat eosinophils have been showed to respond chemotactically to the supernatant from mast cells which have been disrupted by freezing and thawing and from mast cells which have been specifically degranulated by Compound 48/80 or by antigen challenge or sensitised cells. The fact that the chemotactic response is not dependent on allergic degranulation suggests that the chemotactic factor is present pre-formed in the mast cells rather than being generated in response to an antigen-antibody reaction.