Northwick Park Hospital

About: Northwick Park Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Blood pressure. The organization has 4387 authors who have published 4184 publications receiving 192933 citations.

Identification and progression of a desmoid precursor lesion in patients with familial adenomatous polyposis.

Abstract: Background Desmoid tumours occur in about 10 per cent of patients with familial adenomatous polyposis (FAP), and are an important cause of morbidity and death. The natural history of desmoids was investigated by documenting prospectively the prevalence and progression of possible precursor lesions. Methods A group of patients with FAP and controls were examined at laparotomy. Another group, with FAP and no clinical evidence of desmoid, and a group of controls, underwent abdominopelvic computed tomography. Results At laparotomy 13 of 42 patients with FAP had fibromatous mesenteric plaques; seven of these had not had surgery. Seven had more extensive mesenteric fibromatosis and had undergone significantly more laparotomies than the rest. Of 103 patients scanned, two had desmoid tumours and 22 (21 per cent) had mesenteric fibromatosis. On follow-up both desmoid tumours grew rapidly; mesenteric fibromatosis was unchanged in eight and resolved in four of the 12 patients rescanned. Conclusion A model of desmoid tumour development is suggested, analogous to the adenoma–carcinoma sequence, in which a less benign phenotype emerges as molecular genetic abnormalities accumulate: mesenteric plaque-like desmoid precursor lesions arise in many patients with FAP before surgery as a result of abnormal fibroblast function; some, perhaps stimulated by surgery, progress to mesenteric fibromatosis; these in turn can give rise to desmoid tumours. © 1998 British Journal of Surgery Society Ltd

Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder

Abstract: Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.

Infection biology of a novel alpha-crystallin of Mycobacterium tuberculosis: Acr2.

Abstract: Heat shock proteins assist the survival of Mycobacterium tuberculosis (MTB) but also provide a signal to the immune response. The gene most strongly induced by heat shock in MTB is Rv0251c, which encodes Acr2, a novel member of the α-crystallin family of molecular chaperones. The expression of acr2 increased within 1 h after infection of monocytes or macrophages, reaching a peak of 18- to 55-fold by 24 h. Inhibition of superoxide action reduced the intracellular increase in acr2. Despite this contribution to the stress response of MTB, the gene for acr2 appears dispensable; a deletion mutant (Δacr2) was unimpaired in log phase growth and persisted in IFN-γ-activated human macrophages. Acr2 protein was strongly recognized by cattle with early primary Mycobacterium bovis infection and by healthy MTB-sensitized people. Within the latter group, those with recent exposure to infectious tuberculosis had, on average, 2.6 times the frequency of Acr2-specific IFN-γ-secreting T cells than those with more remote exposure (p = 0.009). These data show that, by its up-regulation early after entry to cells, Acr2 gives away the presence of MTB to the immune response. The demonstration that there is infection stage-specific immunity to tuberculosis has implications for vaccine design.

Experiences of living with chronic back pain: the physical disabilities.

Abstract: Purpose Back-related functional limitations are largely assessed using lists of activities, each scored on a yes/no basis and the scores then summed This provides little information about how chronic back pain (CBP) patients live with their condition This study describes the consequences of living day-to-day with CBP and documents the ‘insider’ accounts of its impact on daily lifeMethod Unstructured interviews, using the ‘Framework’ approach with topic guide, were recorded and transcribed verbatim Subjects were sampled for age, sex, ethnicity and occupation from new referrals with back pain to a rheumatology outpatient clinic Eleven subjects (5 male, 6 female) were interviewed either in English (n = 9) or their preferred language (n = 2) Interviews were read in-depth twice to identify the topics Data were extracted in phrases and sentences using thematic content analysisResults Four themes emerged: sleep/rest, mobility, independence and leisure All subjects reported issues about sleep and rest