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Institution

St Thomas' Hospital

HealthcareLondon, United Kingdom
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.


Papers
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Journal ArticleDOI
TL;DR: Feeding a diet rich in lard to pregnant rats leads to gender-related cardiovascular dysfunction in normally fed offspring, andothelium-dependent relaxation to acetylcholine was blunted in male and female offspring of lard-fed dams.
Abstract: Epidemiological studies suggest an association between maternal nutrition and offspring cardiovascular disease. We previously demonstrated endothelial dysfunction and abnormal aortic fatty acid composition in adult female offspring of rats fed animal lard during pregnancy. We have now further investigated this model. Female Sprague-Dawley rats were fed a control breeding diet (5.3% fat) or a diet rich in lard (25.7% fat) 10 days before and throughout pregnancy and lactation. Male and female offspring were implanted with radiotelemeters for recording of blood pressure, heart rate, and activity at 80, 180, and 360 days of age. Reactivity to acetylcholine and to nitric oxide were assessed in isolated small mesenteric arteries from 80- and 180-day-old littermates. Systolic blood pressure (awake phase) was raised in female offspring (180 days: offspring of control, 130.7±1.6 mm Hg, n=5, versus offspring of lard-fed, 138.1±2.9, n=5, P=0.029; 360 days: offspring of control, 129.7±3.7 mm Hg, n=6, versus offspring of lard-fed, 142.1±3.2, n=6, P=0.005). Diastolic blood pressure was also raised at 180 days (offspring of control, 87.6±1.0 mm Hg, n=5, versus offspring of lard-fed, 94.7±2.6, n=5, P=0.011). Blood pressure was not raised in male offspring. Endothelium-dependent relaxation to acetylcholine was blunted in male and female offspring of lard-fed dams (80 and 180 days). Feeding a diet rich in lard to pregnant rats leads to gender-related cardiovascular dysfunction in normally fed offspring.

382 citations

Journal ArticleDOI
TL;DR: It is proposed that a very short period of ischemia and reperfusion "preconditions" the myocardium so as to influence the vulnerability of the heart to subsequent reperfusions-induced arrhythmias, and that "recovery" from this effect can take a substantial period of time.
Abstract: Hearts of anesthetized rats (n = 12 in each of 7 groups) were subjected to 5 min of regional ischemia; on reperfusion, 100% exhibited ventricular tachycardia (VT), 83% ventricular fibrillation (VF), and the mean total number of premature ventricular complexes (PVC) was 681 +/- 220. Hearts were then reverted to sinus rhythm and allowed to "recover" for 10, 20, 30, 60, 120 min, 1 or 3 days; they were again subjected to 5 min of ischemia and reperfusion. With recovery periods of 10 and 20 min a second episode of ischemia and reperfusion resulted in very few arrhythmias: 0% VF in both instances, 17 and 8% VT, and only 4 +/- 3 and 9 +/- 5 PVC, respectively. As the recovery period increased to 3 days there was a progressive return of vulnerability to reperfusion-induced arrhythmias. However, this return was slow, such that with a recovery time of 60 min, only 33% of hearts fibrillated. In additional studies, hearts were subjected to 0.5, 1.0, 3.0, or 5 min of regional ischemia, 10 min of reperfusion, 5 min of ischemia, and a second period of reperfusion. The vulnerability to arrhythmias during the second period of reperfusion was found to correlate inversely with the incidence of arrhythmias elicited by the first episode of reperfusion. We propose that a very short period of ischemia and reperfusion "preconditions" the myocardium so as to influence the vulnerability of the heart to subsequent reperfusion-induced arrhythmias, and that "recovery" from this effect can take a substantial period of time.

381 citations

Journal ArticleDOI
TL;DR: Both early and late menopause were found to be significantly influenced by genetic factors, providing convincing evidence for the importance of genetic factors in determining natural and surgicalMenopause.
Abstract: A classical twin study was performed to assess the extent to which genetic factors explain individual differences in age at menopause and (indications for) hysterectomy. It was further examined whether a genetic effect on the timing of the menopause was mediated through a genetic effect on age at menarche. The subjects were 275 monozygotic and 353 dizygotic female twin pairs. Maximum likelihood model fitting was used to estimate genetic and environmental variance components, Kaplan-Meier survival analysis was used to account for censored data, and the Cox proportional hazards model was used to adjust for potential confounders. A model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability (h2) for age at menopause of 63%. The significance of the genetic effect was confirmed by the survival analysis and was not affected by adjustment for confounders. Both early and late menopause were found to be significantly influenced by genetic factors. Hysterectomy also showed considerable heritability (h2 = 59%), as did its two main indications: fibroids (h2 = 69%) and menorrhagia (h2 = 55%). The genetic contribution to the variance in age at menarche was estimated to be 45%, with the majority (37%) being due to dominant genetic effects. No correlation was found between age at menopause and age at menarche, suggesting different genetic mechanisms. This study provides convincing evidence for the importance of genetic factors in determining natural and surgical menopause. Understanding how genes control the timing of menopause and exploring whether these genes are indirectly associated with disease are important areas for future study.

379 citations

Journal ArticleDOI
TL;DR: Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC, and is a suitable replacement for i.V.5-FU as the backbone of colorectal cancer therapy.
Abstract: This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 mg m(-2) twice daily, days 1-14 every 21 days; n=603) or intravenous (i.v.) bolus 5-fluorouracil/leucovorin (5-FU/LV; Mayo Clinic regimen; n=604). Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV (26 vs 17%; P<0.0002). Subgroup analysis demonstrated that capecitabine consistently resulted in superior response rates (P<0.05), even in patient subgroups with poor prognostic indicators. The median time to response and duration of response were similar and time to progression (TTP) was equivalent in the two arms (hazard ratio (HR) 0.997, 95% confidence interval (CI) 0.885-1.123, P=0.95; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV, respectively). Multivariate Cox regression analysis identified younger age, liver metastases, multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP. Overall survival was equivalent in the two arms (HR 0.95, 95% CI 0.84-1.06, P=0.48; median 12.9 vs 12.8 months, respectively). Capecitabine results in superior response rate, equivalent TTP and overall survival, an improved safety profile and improved convenience compared with i.v. 5-FU/LV as first-line treatment for MCRC. For patients in whom fluoropyrimidine monotherapy is indicated, capecitabine should be strongly considered. Following encouraging results from phase I and II trials, randomised trials are evaluating capecitabine in combination with irinotecan, oxaliplatin and radiotherapy. Capecitabine is a suitable replacement for i.v. 5-FU as the backbone of colorectal cancer therapy.

378 citations

Journal ArticleDOI
TL;DR: In this paper, the efficacy and safety of excimer laser photorefractive keratectomy was evaluated in 120 patients with follow-up, 12 to 22 months, and mean, 18 months.

378 citations


Authors

Showing all 12132 results

NameH-indexPapersCitations
David J. Hunter2131836207050
Rory Collins162489193407
Steven Williams144137586712
Geoffrey Burnstock141148899525
Nick C. Fox13974893036
Christopher D.M. Fletcher13867482484
David A. Jackson136109568352
Paul Harrison133140080539
Roberto Ferrari1331654103824
David Taylor131246993220
Keith Hawton12565755138
Nicole Soranzo12431674494
Roger Williams122145572416
John C. Chambers12264571028
Derek M. Yellon12263854319
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20237
202235
2021654
2020595
2019485
2018462