Churchill Hospital

About: Churchill Hospital is a healthcare organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Transplantation. The organization has 3548 authors who have published 5357 publications receiving 304275 citations.

Anatomic and functional imaging of metastatic carcinoid tumors.

Abstract: Carcinoid tumors are a fascinating group of neuroendocrine neoplasms that develop either sporadically or as part of an inheritable syndrome. Many tumors arise in the bronchopulmonary or gastrointestinal tract, but a neuroendocrine tumor can arise in almost any organ. The tumors have varied malignant potential depending on the site of their origin, and the clinical manifestations often are nonspecific. Metastases may be present at the time of diagnosis, which often occurs at a late stage of the disease. Imaging plays a pivotal role in the localization and staging of neuroendocrine tumors and in monitoring the treatment response. Imaging is often challenging, and a combination of anatomic and functional techniques is usually required, depending on the tumor type and location. Techniques include ultrasonography, barium studies, endoscopy, computed tomography, magnetic resonance imaging, somatostatin receptor scintigraphy, iobenguane scintigraphy, and, in select cases, positron emission tomography. Coregistra...

Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with High-Level Fluoroquinolone Resistance in Vietnam

Abstract: Consecutive fluoroquinolone (FQ)-resistant isolates (n = 109) identified at the Pham Ngoc Thach Hospital for Tuberculosis, Ho Chi Minh City, Vietnam, were sequenced in the quinolone resistance-determining regions of the gyrA and gyrB genes and typed by large sequence polymorphism typing and spoligotyping to identify the Beijing genotype of Mycobacterium tuberculosis Beijing genotype prevalence was compared with 109 consecutive isolates from newly presenting patients with pulmonary tuberculosis from the hospital outpatient department Overall, 826% (n = 90/109) of isolates had mutations in gyrAB Nine novel mutations were identified in gyrB (S486F, N538T, T539P, D500A, D500H, D500N, G509A, E540V, and E540D) The influence of these novel gyrB mutations on FQ resistance is not proven The Beijing genotype was significantly associated with FQ resistance (odds ratio [OR], 239 [95% confidence interval {CI}, 134 to 425]; P = 0003) Furthermore, Beijing genotype FQ-resistant isolates were significantly more likely than FQ-resistant isolates of other genotypes to have gyrA mutations (OR, 775 [95% CI, 284 to 2115]; P = 00001) and high-level (>8 microg/ml) FQ resistance (OR, 110 [95% CI, 26 to 470]; P = 0001) The underlying mechanism of the association of the Beijing genotype with high-level FQ resistance in this setting remains to be determined The association of the Beijing genotype with relatively high-level FQ resistance conferred by specific gyrA mutations reported here is of grave concern given the epidemic spread of the Beijing genotype and the current hopes for shorter first-line treatment regimens based on FQs

Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells

Abstract: Haemophilia B, or Christmas disease, is an inherited X-chromosome-linked bleeding disorder caused by a defect in clotting factor IX and occurs in about 1 in 30,000 males in the United Kingdom1. Injection of factor IX concentrate obtained from blood donors allows most patients to be successfully managed. However, because of impurities in the factor IX concentrate presently in use, this treatment involves some risk of infection by blood-borne viruses such as non-A, non-B hepatitis and the virus causing acquired immune deficiency syndrome (AIDS)2. Because of the recent concern about the increasing incidence of AIDS amongst haemophiliacs, a factor IX preparation derived from a source other than blood is desirable. Here, we report that after introduction of human factor IX DNA clones3 into a rat hepatoma cell line using recombinant DNA methods, we were able to isolate small amounts of biologically active human factor IX.

Mutations in HNF1A result in marked alterations of plasma glycan profile.

Abstract: A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction.

Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria.

Abstract: Summary Background Adherence to antimalarial drug regimens is improved by simple dosing. If the fixed antimalarial drug combination artemether–lumefantrine (AL) could be given once daily, this should improve adherence and thus effectiveness and lower the risk of selecting for resistance. Methods In an open randomized study, 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days. The primary end point was a comparison of the areas under the plasma lumefantrine concentration–time curves (AUC). Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles. Results Lumefantrine pharmacokinetic profiles were obtained for 36 patients. The AUC(0∞) of the once-daily regimen was 30% lower than that in the conventional regimen (P = 0.011) with a median (range) value of 306 (114–5781) μg/ml h, compared with 432 (308–992) μg/ml h. There was no significant difference in the peak plasma concentrations reached. PCR-adjusted cure rate estimates at day 42 of follow-up were 94% (95% CI: 84–100) in the six-dose arm and 85% (70–100) in the three-dose arm (P = 0.3). Conclusion Artemether–lumefantrine efficacy is reduced by once-daily dosing, because absorption of lumefantrine is dose limited. At currently recommended doses, this antimalarial should be given twice daily in a 3-day regimen, with food containing fat. Donnees de base La compliance aux traitements a base d'antimalariques est amelioree par des doses simples. Si la combinaison a dose fixe d'antimalariques artemether–lumefantrine pouvait etre administree une fois par jour, cela devrait ameliorer la compliance et donc l'efficacite, et reduire le risque de selection de resistance. Methodes dans une etude randomisee ouverte, 43 patients presentant une malaria falciparum non compliquee ont recu des doses equivalentes d'artemether–lumefantrine avec 200 ml de lait aromatise, selon le regime conventionnel i.e: deux fois par jour ou selon un regime a une seule dose quotidienne pendant 3 jours. L'objectif final primaire etait la comparaison des aires sous la courbe (AUC) de la concentration plasmatique de lumefantrine en fonction du temps. Les objectifs secondaires etaient la mesure des taux de guerison ajustes par les resultats de la reaction en chaine de la polymerase (PCR) au jour 42ieme et les profils de tolerance. Resultats Les profils pharmacocinetiques de lumefantrine ont ete obtenus pour 36 patients. Les AUC(0∞) dans le regime ‘‘une fois par jour’’etait 30% inferieur a celles dans le regime conventionnel (p = 0,011) avec une valeur mediane de 306 (114–5781) μg/ml h comparea 432 (308–992) μg/ml h. Il n'y avait aucune difference significative dans les concentrations plasmatiques maximales atteintes. Les taux de guerison ajustes par la PCR au 42ieme jour du suivi etaient de 94% (IC95%: 84–100) dans le groupe a 6 doses et 85% (IC95%: 70–100) dans le groupe a 3 doses (p = 0,3). Conclusion L'efficacite de l'Artemether–lumefantrine est reduite dans le regime ‘'une fois par jour‘’ parce que l'absorption du lumefantrine est dose dependante. Aux doses recommandees actuellement, cet antimalarique devrait etre administre deux fois par jour dans un regime de trois jours, avec la nourriture contenant la matiere grasse. Antecedentes La adherencia al tratamiento con antimalaricos mejora si se simplifica la dosificacion. Si se pudiese dar la combinacion fija de antimalaricos artemeter–lumefantrina (AL) en una dosis unica por dia, deberia mejorar la adherencia y por lo tanto la efectividad del tratamiento, habiendo un menor riesgo de seleccion de cepas resistentes. Metodos En un ensayo abierto, aleatorizado, en el que 43 pacientes con malaria no complicada por falciparum recibieron durante tres dias dosis equivalentes de AL con 200ml de leche, bien bajo el regimen convencional de dos veces al dia o en una dosis unica cada dia. El criterio principal de valoracion fue una comparacion de las areas bajo las curvas de la concentracion de lumefantrina en plasma a lo largo del tiempo (ABC). Los criterios secundarios de valoracion fueron las PCR del dia 42, las tasas de curacion ajustadas y los perfiles de tolerabilidad. Resultados Se obtuvieron los perfiles farmacocineticos de la lumefantrina para 36 pacientes. El ABC (0∞) del regimen unico al dia era un 30% mas bajo que el regimen convencional (p = 0.011) con una media (rango) de 306 (114–5781) μg/ml h comparado con 432 (308–992) μg/ml h. No habia una diferencia significativa entre las maximas concentraciones de plasma alcanzadas. Las tasas de curacion ajustadas por PCR a los 42 dias de seguimiento fueron 94% (95%CI 84–100) para el grupo con 6 dosis y 85% (70–100) para los que recibieron 3 dosis (p = 0.3). Conclusion La eficacia de artemeter–lumefantrina se reduce al dar una dosis unica, puesto que la absorcion de la lumefantrina esta limitada por la dosis. En las dosis recomendadas en la actualidad, este antimalarico deberia darse dos veces al dia en un regimen de tres dias, acompa,nado con alimentos que contengan grasas.