St Thomas' Hospital

About: St Thomas' Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Pregnancy. The organization has 12105 authors who have published 15596 publications receiving 624309 citations. The organization is also known as: St Thomas's Hospital & St. Thomas's.

The Autosomal Dominant Hypophosphatemic Rickets (ADHR) Gene Is a Secreted Polypeptide Overexpressed by Tumors that Cause Phosphate Wasting

Abstract: The gene mutated in autosomal dominant hypophosphatemic rickets (ADHR), a phosphate wasting disorder, has been identified as FGF-23, a protein that shares sequence homology with fibroblast growth factors (FGFs). Patients with ADHR display many of the clinical and laboratory characteristics that are observed in patients with oncogenic hypophosphatemic osteomalacia (OHO), a disorder thought to arise by the secretion of a phosphate wasting factor from different mesenchymal tumors. In the present studies, we therefore investigated whether FGF-23 is a secreted factor and whether it is abundantly expressed in OHO tumors. After transient transfection of OK-E, COS-7, and HEK293 cells with the plasmid encoding full-length FGF-23, all three cell lines efficiently secreted two protein species into the medium that were approximately 32 and 12 kDa upon SDS-PAGE and subsequent Western blot analysis using an affinity-purified polyclonal antibody to FGF-23. Furthermore, Northern blot analysis using total RNA from five different OHO tumors revealed extremely high levels of FGF-23 mRNA, and Western blot analysis of extracts from a sixth tumor detected the 32 kDa FGF-23 protein species. In summary, FGF-23, the gene mutated in ADHR, is a secreted protein and its mRNA is abundantly expressed by several different OHO tumors. Our findings indicate that FGF-23 may be a candidate phosphate wasting factor, previously designated "phosphatonin".

Juvenile Myoclonic Epilepsy: A 5-Year Prospective Study

Abstract: Summary: We made a long term prospective study of 66 patients with juvenile myoclonic epilepsy (JME). Prevalence was 10.2% among 672 patients with epilepsies. Sex distribution was equal. Sixty-three were not diagnosed on referral; JME was not initially recognized in the epilepsy clinic in 22. Clinical typical absence seizures were reported in 33.3%, myoclonic jerks in 97% and generalized tonic-clonic seizures (GTC) in 78.8% of the patients. Mean age (±SD) at onset was 10.5 ± 3.4 years (range 5–16 years) for absence seizures, 15 ± 3.5 years (range 8–26 years) for myoclonic jerks, and 16 ± 3.5 years (9–28) for GTC. Absence predated myoclonic jerks by 3.9 ± 2.3 years (range-1–9 years) and GTC by 4.4 ± 2.7 years (range 1–8 years) in 14 (21.2%) patients who manifested all three types of seizure. Absence were never antedated by myoclonic jerks or GTC. Myoclonic jerks occurred on awakening in 87.5% of the patients. GTC occurred mainly on awakening, but other patients had nocturnal or diurnal GTC with no circadian distribution. Neurologic examination was normal for all patients except for tremor of the hands similar to essential tremor, noted in 35% of patients. Computed tomography (CT) brain scans were normal: 93% of patients had precipitating factors: sleep deprivation (89.5%), fatigue (73.7%), photosensitivity (36.8%; television and video games 8.8%), menstruation (24.1% of women), mental concentration (22.8%), and stress (12.3%). Incidence of JME among siblings (13 of 41 examined families) implies an autosomal recessive mode of inheritance for this Arab population. EEGs were frequently normal in treated patients. At least one abnormal EEG was recorded in 56 (84.9%) patients. Abnormalities consisted mainly of generalized discharges of spike/double spike and/or polyspike and slow wave. Frequent multiple spikes and discharge fragmentations varied from 0.5to 20-s duration (mean 6.8 s). Twenty (30.3%) had focal abnormalities, and 18 (27.3%) had photoconvulsive discharges. Eighty-eight percent of patients remained seizure-free for 3 years of follow-up. Effective treatment was achieved with valproate (VPA); control of myoclonic jerks was improved with clonazepam (CZP). CZP monotherapy did not consistently prevent GTC. Adding small doses of CZP with simultaneous reduction of VPA was the most effective and better tolerated form of medication, particularly in patients demonstrating an adverse reaction or requiring a large VPA dosage. VPA dosage was successfully reduced in 15 patients who were seizure-free for >2 years and had infrequent seizures before treatment, but 9 of 11 patients relapsed after VPA discontinuation. ReSUMe Les auteurs ont entrepris une etude prospective a long terme de 66 patients presentant une epilepsie myoclonique juvenile (EMJ). La prevalence etait de 10.2% parmi 672 patients presentant une epilepsie. La distribution entre les sexes etait egale. Soixante trois patients n'etaient pas diagnostiques au moment de leur premier contact; l'epilepsie myoclonique juvenile n'avait pas ete reconnue initialement dans la consultation epileptologique chez 22 patients. Les absences cliniques etaient reporetes chez 33.3%, des secousses myocloniques chez 97% et des crises tonico-cloniques chez 78.8% des patients. L'âge moyen du debut etait de 10.5 ± 3.4 ans (±SD, limite 5 a 16) pour les absences, 15 ± 3.5 (8 a 26) pour les secousses myocloniques et 16 ± 3.5 (9 a 28) pour les crises generalisees tonico-cloniques. Les absences precedaient les myoclonies de 3.4 ± 2.3 annees (de 1 a 9) et les crises generalisees tonico-cloniques de 4.4 ± 2.7 annees (1 a 8) chez les 14 patients (21.2%) qui presentaient les trois types de crises. Les absences n'ont jamais ete precedees par des secousses myocloniques ou par des crises generalisees tonicocloniques. Les secousses myocloniques etaient constatees au reveil chez 87.5% des patients. Les crises generalisees tonicocloniques survenaient principalement au reveil, mais d'autres patients avaient des crises nocturnes ou diurnes sans distribution circadienne. L'examen neurologique etait normal chez tous les patients, en dehors d'un tremblement des mains semblable au tremblement essentiel, constatt chez 35% des patients. Les scanners cerebraux ont toujours ete normaux. Les facteurs declenchant des crises ont ete constates chez 93% des patients: privation de sommeil chez 89.5%, fatigue chez 73.7%, photosensibilite chez 36.8% (television et jeux video 8.8%), menstruation chez 24.1% des femmes, concentration mentale chez 22.8%, stress chez 12.3%. L'incidence de l'EMJ dans les fratries (13 des 41 familles examinees) implique un mode de transmission autosomique recessif dans cette population d'origine arabe. Les EEG etaient souvent normaux chez les patients traites. Au moins un EEG anormal a ete enregistre chez 56 patients (84.9%). Les anomalies ttaient representtes surtout par des decharges generalisees de pointes, doubles pointes ou poly pointes-ondes lentes. La duree des pointes multiples et des fragmentations des decharges variaient de 0.5 a 20 secondes (en moyenne 6,8 secondes). Les anomalies focales ont ete constatees chez 20 patients (30.3%) et des decharges photoconvulsives chez 18 patients (27.3%). Quatre vingthuit pour cent des patients sont restes sans crise pendant 3 ans ou plus de suivi. Le traitement efficace a utilise le valproate (VPA). Le controle des secousses myocloniques a ete ameliore avec le clonazepam (CZP). Une monotherapie par CZP n'a pas permis de prevenir de facon constante les crises generalisees tonico-clonique. Une substitution partielle utilisant le valproate, avec de petites doses de CZP, a ete le traitement le plus efficace et le mieux tolere, particulierement chez les patients presentant des effets secondaires ou necessitant de fortes doses de VPA. La dose de VPA a ete reduite avec succes chez 14 patients qui n'avaient plus de crises depuis plus de 2 ans et qui n'avaient que de rares crises avant le traitement. Cependant, 9 patients sur 11 ont recidive aprts l'arret du VPA. RESUMEN Los autores han llevado a cabo un estudio prospectivo a largo plazo de 66 enfermos con Epilepsia Mioclonica Juvenil (JME). La prevalencia fue de 10.2% en 672 casos con epilepsia. La distribucion entre sexos fue equivalente. Sesenta y tres casos no habian sido diagnosticados por quienes enviaban los enfermos y la JME no fue reconocida inicialmente en la clinica de epilepsia en 22 sujetos. Los tipicos ataques de ausencia clinica aparecieron en 33.3%, los movimientos mioclonicos en 97% y los ataques generalizados tonico-clonicos (GTCs) en 78.8% de los enfermos. La edad media (tSD)a1 comienzo fue de 10.5 ± 3.4 (rango 5–16) ahos para las ausencias, 15 ± 3.5 (8–26) para los movimientos mioclonicos y 16 ± 3.5 (9–28) para los GTCs. Las ausencias precedieron a los movimientos mioclonicos en 3.4 ± 2.3 anos (rango 1–9) y en 4.4 ± 2.7 a los GTCs (rango 1–8) y en 14 anos (21.2%) en enfermos que presentaban los tres tipos de ataques. Las ausencias nunca fueron precedidas de ataques mioclonicos o GTCs. Las mioclonias se presentaron durante la vigilia en 87.5% de los enfermos. Los GTCs predominaron durante la vigilia pero otros enfermos tenian GTCs nocturnos o diurnos sin distribucion circadiana. La exploracidn neurologica fue normal en todos los pacientes con la excepcion de temblor en las manos semejante al temblor esencial que aparecio en el 35% de los enfermos. El CT de cerebro fue normal. En el 93% de los enfermos se encontraron factores precipitantes: la deprivacion del suedo en 89.5%, la fatiga en 73.7%, la fotosensibilidad en 36.8% (television y juegos de video en 8.8%), la menstruation en el 24.1% de las mujeres, el retraso mental en el 22.8% y el stress en el 12.3%. La incidencia de los JME entre hermanos (13 en 41 de las familias examinadas) sugiere un modo autosomico recesivo de herencia para esta poblacion Qrabe. Los EEGs fueron frecuentemente normales en los enfermos tratados. A1 menos un EEG anormal fue registrado en 56 enfermos (84.9%). Las anomalias consistieron, generalmente, en descargas generalizadas de puntddoble punta ylo polipuntas y ondas lentas. La frecuencia de las mliltiples puntas y la fragmentacion de las descargas variaron de 0.5–20 s (promedio 6.8 s) de duracion. Las anomalias focales se observaron en 20 (30.3%) y las descargas fotoconvulsivas en 18(27.3%) pacientes. El 88% de los enfermos permanecieron libres de ataques durante 3 o mas anos de seguimiento. La eficacia del tratamiento se consiguio con valproato (VPA) que controlo los movimientos mioclonicos y mejoro con clonazepam (CZP). La monoterapia con CZP no evito de mod0 consistente las GTCs. La sustitucion parcial de VPA por dosis bajas de CZP fue la medicacion mas eficaz y mejor tolerada particularmente en enfermos que demostraban reacciones adversas o requerian dosis altas de VPA. La reduccibn de las dosis de VPA fue posible en 14 enfermos que estaban libres de ataques durante mas de 2 afios y habian tenido ataques infrecuentes antes del tratamiento. Sin embargo 9 de 11 pacientes volvieron a tener episodios a1 interrumpir el VPA.

Oxidative Stress and Preeclampsia: Rationale for Antioxidant Clinical Trials

Abstract: Preeclampsia remains a frequent and potentially dangerous complication of pregnancy. The cause remains largely unknown, but oxidative stress and a generalized inflammatory state are features of the maternal syndrome. The placenta appears to be the principal source of free radical synthesis but maternal leukocytes and the maternal endothelium are also likely contributors. Recent reports have suggested an important role for placental trophoblast NAD(P)H oxidase in free radical generation in preeclampsia. The antioxidant vitamin E is now known to have multiple actions in addition to prevention of lipid peroxidation (ie, inhibition of NAD(P)H oxidase activation and the inflammatory response). In view of the abnormally low plasma vitamin C concentrations in preeclampsia, a combination of vitamins C and E is a promising prophylactic strategy for prevention of preeclampsia. Several multicenter randomized clinical trials are now underway. The potential use of antioxidants and the recognized, albeit modest, benefit of low-dose aspirin prophylaxis have heightened the need for a reliable predictive test for preeclampsia. A combination test involving several relevant biomarkers is likely to provide the best predictive potential.

A Long-term Follow-up of Stroke Patients

Abstract: Background and Purpose Two hundred ninety-one residents of southeast London, younger than 75 years, suffered their first stroke in 1989/1990. The objectives of this study were to determine the long-term outcome of this cohort of stroke patients in terms of impairment, disability, handicap, and quality of life and their use of services and prevention measures subsequent to their stroke. Methods The survivors and their identified caregivers were traced and completed a structured interview questionnaire that included the Barthel Index, modified Rankin Scale, Hospital Anxiety and Depression Scale (HAD), Mini-Mental State Examination, Frenchay Activities Index, and Caregiver Strain Index. Results One hundred twenty-three people (42%) were alive, of whom 106 were interviewed. The mean interval between the stroke and the long-term follow-up was 4.9 years. Thirty-one of the survivors (29%) were severely or moderately disabled, 39 (37%) were mildly disabled, and 36 (34%) were functionally independent. Of the 96 pe...

Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity.

Abstract: OBJECTIVES--The natural history of knee osteoarthritis (OA) is poorly understood. The principal aim was to assess the rate of contralateral knee OA in middle aged women in the general population with existing unilateral disease and to identify the major factors that influence this rate. METHODS--Fifty eight women aged (45-64) from a general population study cohort were identified with unilateral knee OA diagnosed radiologically (Kellgren and Lawrence 2+) (K&L). Follow up AP films were obtained at 24 months and compared with the baseline for K&L grade and individual features of osteophytes and joint space. RESULTS--Twenty women (34%) developed incident disease in the contralateral knee (based on K&L 2+ or osteophyte changes) and 22.4% (n = 13) of women progressed radiologically in the index joint. Obesity at baseline was the most important factor related to incident disease, 47% of women in the top BMI tertile developed OA, compared with 10% in the lowest tertile: relative risk 4.69 (063-34.75). No clear effect was seen for age, physical activity, trauma or presence of hand OA. CONCLUSIONS--Over one third of middle aged women with unilateral disease will progress to bilateral knee OA within two years and a fifth will progress in the index joint. Obesity is a strong and important risk factor in the primary and secondary prevention of OA. These natural history data provide a useful estimate for planning therapeutic intervention trials.