tbuckley/cabot-search huggingface dataset:
Lessons from rat models of hypertension from Goldblatt to genetic engineering
Authors: Y Pinto
Journal: Cardiovascular Research (1998)

Over the past 50 years various animal models of hypertension have been developed, predominantly in the rat. In this review we discuss the use of the rat as a model of hypertension, and evaluate what these models have taught us. Interestingly, the spontaneously hypertensive rat (SHR) is by far the most widely used rat model, although it reflects only a rare subtype of human hypertension, i.e. primary hypertension that is inherited in a Mendelian fashion. Many other aspects of the etiology of hypertension are found in other rat models, but these models are less frequently employed. The widespread use of the SHR suggests that this rat model is often chosen without considering alternative (and possibly better suited) models. To illustrate the importance of the choice for a particular model, we compared the natural history and response to antihypertensive drugs in different rat models of hypertension (SHR, Dahl, deoxycorticosterone acetate (DOCA)–salt, two-kidney one-clip, transgenic TGR(mRen2)27. This revealed that the outcome of hypertension can be similar in some respects, as all models exhibit cardiac hypertrophy, and all demonstrate impaired endothelium-dependent relaxations. However, the more severe forms of end-organ damage such as heart failure, stroke and kidney failure, occur only in some models and then only in a subset of the hypertensive rats. The effects of antihypertensives varies even more in the different models: antihypertensive treatment only attenuates end-organ damage if it decreases blood pressure. Moreover, if a given antihypertensive is effective, it sometimes even attenuates end-organ damage in nonhypotensive doses. On the other hand, some agents do decrease blood pressure but do not prevent end-organ damage (e.g. hydralazine in SHR). Furthermore, not all classes of antihypertensives are equally effective in all rat models of hypertension: endothelin-receptor antagonists are not effective in SHR, but have beneficial effects in the DOCA–salt model. The comparison of models, and the comparison of treatment effects suggests that end-organ damage critically depends upon not only on the stress imposed by high blood pressure and its underlying biochemical disturbance, but also upon the ability of the organism to recruit adequate 'coping' mechanisms. These coping mechanisms deserve greater attention, as failure to recruit such mechanisms may indicate an increased risk. The current development of transgenic techniques will provide new opportunities, to develop specific models to address this balance between stress and coping.
Clinical Significance of Malignant Neoplasms of the Thyroid Gland
Authors: Walter F. Rogers, Samuel P. Asper, Robert H. Williams
Journal: New England Journal of Medicine (1947)

THE value of extirpating goiters, particularly nodular ones, for the prevention of malignant neoplasms of the thyroid gland has been the subject of considerable discussion for many years. Opinions have ranged from a conservative attitude to one of removing all goiters containing nodules, whether single or multiple.1 , 2 In the presence of these divergent opinions, the frequency with which prophylactic thyroidectomies should be performed needs evaluation.There are numerous reports in the literature concerning the incidence of malignant neoplasms of the thyroid gland.1 2 3 4 5 6 7 In two recent reports the incidence of carcinoma was particularly high, Cole et al.7 stating that the incidence . . .
The Efficacy of Live Attenuated, Cold-Adapted, Trivalent, Intranasal Influenzavirus Vaccine in Children
Authors: Robert B. Belshe, Paul M. Mendelman, John Treanor, James King, William C. Gruber, Pedro Piedra, David I. Bernstein, Frederick G. Hayden, Karen Kotloff, Ken Zangwill, Dominick Iacuzio, Mark Wolff
Journal: New England Journal of Medicine (1998)

Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old.
PWE-121 Non-alcoholic steatohepatitis in patients with diabetes mellitus: as clinicians how good are we at identifying patients at risk?
Authors: VJ Appleby, M Owen, S Moreea
Journal: Gut (2015)

<h3>Introduction</h3> Over the past thirty years the number of people with diabetes mellitus (DM) has more than doubled globally and the WHO predicts that DM will be the seventh leading cause of death by 2030. DM is a causative factor of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Presently raised alanine transaminase (ALT) is used as a marker for NAFLD however it is recognised that ALT is not a sensitive marker for either diagnosing or assessing the severity of NAFLD. Ultrasound is a better method of disease detection and the degree of fibrosis can be documented using elastography. <h3>Method</h3> We aimed to determine the prevalence of NAFLD and extent of liver fibrosis in an unselected population of subjects with DM attending outpatient clinics in secondary care. Secondary endpoints included determining whether there were any differences in ALT levels and liver stiffness scores between subjects with type 1(T1) and type 2(T2)DM. On five separate occasions we attended DM clinics offering fibroscans to patients (pts) waiting to be seen. We also collected data on age, sex, weight, height; liver function tests (LFTs), alcohol intake and type of diabetes. <h3>Results</h3> We performed fibroscans on 45 pts; 25 T1DM (15 females (F) age range (AR) 31–67, median age (MA) 42; 10 males (M) AR 22–84, MA 45) and 20 with T2DM (17M; AR23–72, MA54 and 3F;AR 31–58, MA44). All pts consumed less than the government recommended units of alcohol. In the T1DM cohort, median BMI: 27; range19–37, median ALT 23 iu/L; range 12–51 iu/L*,median liver stiffness: 4.8 KPa; range 2.8–11.9 KPa (F: median ALT 19 iu/L, liver stiffness 4.7 KPa; M: median ALT 30 iu/L, liver stiffness 5.2 KPa). One pt (F) had METAVIR stage 4 fibrosis on fibroscan. In the T2DM cohort, the median BMI: 31; range 27–40, median ALT 50 iu/L, range 13–119 iu/L, median liver stiffness: 8.9 KPa, range 4.1–21.3 KPa (F: median ALT 21 iu/L, liver stiffness 6.3 KPa; M: median ALT 55 iu/L, liver stiffness 9.1 KPa). Elevated ALT was documented in 13/20 (65%), median liver stiffness: 11.3 KPa (METAVIR stage 4), none of these pts were known to hepatology services. In this cohort scatterplot analysis demonstrated a positive correlation between ALT level and median liver stiffness. *Normal range of ALT: M: &lt;40 iu/L, F: &lt;30 iu/L <h3>Conclusion</h3> In an unselected asymptomatic cohort of DM pts, 16/45 (35%) had raised ALT levels with a prevalence of 24% of advanced fibrosis in this cohort. Abnormal ALT levels and elevated liver stiffness scores were more common in T2DM pts compared to T1DM pts. This study highlights the importance of early identification of pts with risk factors for NASH, regular monitoring of LFTs, reacting to abnormalities and specialist referral for fibrosis assessment using elastography. <h3>Disclosure of interest</h3> None Declared.
Beware — The Anaerobe Bandwagon
Authors: Malcolm I. Page
Journal: New England Journal of Medicine (1974)

Important studies have recently advanced understanding and recognition of the role of anaerobic organisms as a cause of serious infections.1 2 3 4 5 6 7 8 Bornstein et al.1 noted an increase in anaerobic isolations at the Massachusetts General Hospital in the years 1960–63, and a number of institutions in the past few years have reported increased anaerobic isolations as a consequence of improved methods.2 Several special programs and conferences concerning anaerobic infections have been held,9 , 10 and rapid dissemination of this new information has made it a frequent subject of discussion on ward rounds and grand rounds at most major teaching institutions. The result seems to . . .
High correspondence between EGFR mutations in tissue and in circulating DNA form non-small-cell lung cancer (NSCLC) patients (p) with poor performance status (PS)
Authors: T. Moran, L. Paz-Ares, D. Isla, M. Cobo, B. Massuti, A. Insa, C. Queralt, A. Pradas, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2007)

7505 Background: We evaluated the correspondence between EGFR mutations in NSCLC tissue and matched serum DNA and the value of EGFR mutations as a serological marker. Methods: 121 Spanish stage IV NSCLC p received customized first- or second-line erlotinib monotherapy based on the presence of EGFR mutations in the tumor tissue. Serum genomic DNA was obtained from all p prior to erlotinib administration. EGFR exon 19 deletions were studied by length analysis of fluorescently labeled PCR products and the exon 21 L858R mutation by a PCR Taqman assay. Results: The EGFR mutation status in the serum was consistent with that in the tumor tissue of 82/121 p (68%) and of 15/16 p (93.8%) with PS 2 had mutations. Overall, 64.3% of p had an exon 19 deletion and 35.7% had L858R. 78% of mutations were found in females (P=0.01) and 77.6% in never-smokers (P=0.07). Response rate was 88% in p with mutations only in the tumor and 87% in p with mutations in tumor and serum. Complete responses were observed in 20% of p with mutations in tumor and serum vs 4% of p with mutations only in tumor (P=0.09). With a median follow-up of 6.8 months (m) (range, 1.2–17.6), time to progression (TTP) and median survival have not been reached. A trend to better outcome was seen in p without serum EGFR mutations. TTP was longer for p with EGFR exon 19 deletions (not reached) than for p with L858R (7.7 m) (P=0.02). TTP for p with PS 2 with exon 19 deletions was not reached, while it was 2.7 m for p with L858R (P=0.17). Conclusions: EGFR mutations in serum could be a non-invasive source of information on the genotype of the original tumor cells and could be a useful tool to predict p response to erlotinib, especially in p with poor PS. No significant financial relationships to disclose.
Long-Term Responses of the Mouse Uterus to Neonatal Diethylstilbestrol Treatment and to Later Sex Hormone Exposure&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P L Ostrander, K T Mills, H A Bern
Journal: JNCI Journal of the National Cancer Institute (1985)

The effects of ovariectomy at 1 month of age and continuous 17β-estradiol (E2) and/or progesterone (P) replacement on the uterus of BALB/cCrgl mice neonatally treated with diethylstilbestrol [(DES) CAS: 56-53-1; α-α′-diethyl-4,4′-stilbenediol] or sesame oil were recorded after 1, 4, 7, and 10 months of treatment. DES-exposed uteri were found to be hypoplastic, less responsive to the growth-promoting effects of E2, and more likely to develop smooth muscle abnormalities after continuous hormonal treatment than similarly treated control uteri. Neonatal DES treatment led to leukocytic infiltration, disruption in the organization of the inner circular smooth muscle layer, and development of a population of epithelial cells believed to respond to later E2 treatment by proliferation and stratification (squamous metaplasia). Qualitative and quantitative responses to continuous P treatment and the development of cystic glandular hyperplasia and adenomyosis were found to be unaltered by neonatal DES administration. The relevance of these results to the problems of uterine abnormalities observed in women exposed to DES in utero is discussed.
Experiences with the Combined Operation for Cancer of the Head and Neck
Authors: David Lyall, Wilfrid A. Cloutier
Journal: New England Journal of Medicine (1957)

THE study of a series of 60 cases in which mandibular resection in continuity with some type of neck dissection was carried out forms the basis of this preliminary report. It will be seen that our results are somewhat discouraging on a long-term curative basis. On the other hand relief of pain and other distressing symptoms of advanced cancer was frequently dramatic and of significant duration.Experience at first-hand is the only true pathway to wisdom. This is particularly true when one tries to gain maturity of judgment in handling advanced cancers of the head and neck. The experiences of . . .
Importance of duration of radiotherapy (RT) in patients (pts) with locally advanced cervical carcinoma (LACC) treated with concurrent chemoradiotherapy
Authors: J. J. Zarba, F. R. Solórzano, P. Gonzalez Jasey, L. De Gregorio, R. Zelaya, J. R. Arcuri
Journal: Journal of Clinical Oncology (2008)

16576 Background: Duration of radiotherapy is a recognized prognostic factor of outcome of patients (pt) with LACC. It was established that 8 weeks (w) is the cut point of duration of hole RT treatment including brachytherapy (B). Longer duration is related with poor outcome. The role of duration of RT is not well established in concurrent chemoradiotherapy. Objetives: To evaluate the disease free survival in pt with LACC treated with concurrent chemoradiotherapy,according to duration of radiotherapy. Methods: We evaluate the medical records of pts with LACC between 2000 and 2004 treated in our Institution. We selected only pt who complete the hole treatment and with an adecuate follow up.We analize desease free survival regarding the duration of RT of ≤ 8 w or > 8 w. Results: 92 pts were analysed. The characteristics of population were: Median age: 47 years; median follow up: 40 mounths. Stage of desease: Stage IB 4; IIA 4; IIB 36; IIIB 48. Median duration of treatment: 10 w. Median time od B delay: 3 w. 32 pts had a duration of RT ≤ 8 w and 60 pts had a duration of > 8 w. Median DFS: 39 months (m) (5–88); Median DFS for patients with duration of treatment less or more than 8 w was 44 m (7–88) and 36,5 m (5–86), respectively. 18/32 pts (57%) with treatment ≤ 8 w and 26/60 pts (44%) with treatment > 8 w were alive without disease at 40 m. Conclusions: Duration of radiotherapy seems to be a predictor factor of outcome in LACC treated with CCR. No significant financial relationships to disclose.
Abstract A06: The chemokine receptor CXCR4 is essential for the maintenance of T cell acute lymphoblastic leukemia.
Authors: Lauren A. Pitt, Anastasia N. Tikhonova, Thomas Trimarchi, Bryan King, Hai Hu, Yixiao Gong, Aris Tsirigos, Marta Sanchez-Martin, Dan R. Littman, Adolfo Ferrando, Sean J. Morrison, David R. Fooksman, Iannis Aifantis, Susan Schwab
Journal: Clinical Cancer Research (2015)

Abstract T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy arising in immature T cell progenitors. Despite improved survival rates, relapse remains a major therapeutic obstacle and intensive treatment regimens expose T-ALL patients to serious long-term side-effects. Hence more effective, less toxic treatment options are required. While the localization of leukemia cells determines the course of disease, little is known about T-ALL migration. Upon profiling chemokine receptor expression by T-ALL cells, we observed high surface levels of the CXCL12 receptor, CXCR4. Intravital imaging revealed that T-ALL cells are in direct contact with CXCL12-producing bone marrow stromal cells in vivo. Genetic targeting of CXCR4 in T-ALL cells resulted in a marked reduction of leukemia burden and significantly prolonged survival. Moreover, disruption of CXCR4 signaling with a small molecule inhibitor severely impaired T-ALL progression in mouse and human xenograft models of the disease. We found that CXCR4 promotes c-Myc expression, which is required in leukemia initiating cells. Given the relatively subtle role for CXCR4 in normal developing T cells, CXCR4 inhibition to our knowledge has not been proposed as a therapy for T cell malignancies. Our data strongly suggest that targeting CXCR4 could be a promising strategy for combating T-ALL. Citation Format: Lauren A. Pitt, Anastasia N. Tikhonova, Thomas Trimarchi, Bryan King, Hai Hu, Yixiao Gong, Aris Tsirigos, Marta Sanchez-Martin, Dan R. Littman, Adolfo Ferrando, Sean J. Morrison, David R. Fooksman, Iannis Aifantis, Susan Schwab. The chemokine receptor CXCR4 is essential for the maintenance of T cell acute lymphoblastic leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A06.
PTH-348 The outcome of an enhanced recovery programme applied to minimally invasive cytoreductive surgery: Abstract PTH-348 Table 1
Authors: T Bullen, C Selvasekar, G Punnett, R Fish, PE Fulford, MS Wilson, O Aziz, AG Renehan, ST O’Dwyer
Journal: Gut (2015)

<h3>Introduction</h3> Pseudomyxoma peritoneii (PMP) is a rare neoplasm arising from the appendix, characterised by disseminated peritoneal mucinous tumour and progressive accumulation of mucinous ascites. For established disease, treatment by cytoreductive surgery (CRS) and heated intra-peritoneal chemotherapy (HIPEC) is the accepted standard of care.<sup>1</sup>Through a UK national treatment centre, we increasingly identify patients with localised extra- appendiceal mucin without evidence of diffuse dissemination of disease (referred to as LAMN II tumours).<sup>2</sup>We developed a programme of risk-reducing cytoreductive surgery (RCRS) and HIPEC, initially by open surgery (period 1); subsequently by laparoscopically assisted CRS and HIPEC (period 2); and more recently adding an enhanced recovery protocol (ERP) (period 3).<sup>3</sup>Here, we describe key outcome measures through this evolution. <h3>Method</h3> Using a prospective database we recorded patients undergoing RCRS and HIPEC between 2003 and 2014; Operative time and length of stay and morbidity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) were recorded. <h3>Results</h3> Sixty patients with LAMN II appendiceal tumours had RCRS and HIPEC: There was no difference in the demographics or ASA grade. There was no mortality in all groups. <h3>Conclusion</h3> We demonstrate that the combined approach of laparoscopic CRS with HIPEC and ERP in patients with localised LAMN II tumours is associated with very low morbidity and short hospital stay, desirable criteria for a risk-reducing programme. There were no complications due to ERP. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Chua TC, Moran BJ, Sugarbaker PH. Early and long-term outcome data of patients with pseudomyxoma peritoneii from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. <i>J Clin Oncol</i>. 2012;30(20):2449–56 McDonald JR, O’Dwyer ST, <i>et al</i>. Classification of and cytoreductive surgery for low-grade appendiceal mucinous neoplasms. Br J Surg. 99(7):987–92 Fish R, Selvasekar C, <i>et al</i>. Risk-reducing laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for low-grade appendiceal mucinous neoplasm: early outcomes and technique. Surg Endosc. 28(1):341–5
NCO-05LONG TERM FUNCTIONAL AND CLINICAL OUTCOME IN CHILDREN WITH CRANIOPHARYNGIOMA TREATED WITH HIGH PRECISION STEREOTACTIC CONFORMAL RADIOTHERAPY (SCRT): DATA FROM A PROSPECTIVE TRIAL
Authors: jayant Goda, Uday Krishna, savita Goswami, Tejpal Gupta, Nazia Bano, Nalini Shah, Rajiv Sarin, Rakesh Jalali
Journal: Neuro-Oncology (2015)

BACKGROUND: To report prospective detailed outcome data in young patients with residual/recurrent craniopharyngioma treated with Stereotactic Conformal focal radiotherapy (SCRT). METHODS: 39 patients (27 males, 12 females; median age-11 years) underwent prospective detailed serial longitudinal evaluation of neuropsychological/ neurocognitive, and neuroendocrine function at baseline and follow-up after RT. RESULTS: Near total excision as the commonest surgery (82%). Mild/moderate hydrocephalus was observed in 85% and severe in 15%. Impaired vision was observed in 2 patients (5.2%). At a median follow-up of 49.5months (IQ range 12-67 months). 37 patients were controlled at last follow-up with a 10-yr OS of 92% and 10-yr PFS of 84%. Pre-RT mean VQ/MQ, performance IQ (PQ) and FSIQ were 84.95, 80.5 and 77.1 respectively and improved to 96.9,104 and 91 respectively at 5 years follow-up following RT. Pre RT endocrine deficit in 1 or 2 axes was seen in 50% of patients. Involvement of additional axes was seen in 21% patients. LOTCA scores showed improvement with time in attention concentration domain following SCRT. Mean trait-anxiety scores both in children and adolescents was poor at baseline which improved at 5-years follow-up following SCRT. CONCLUSION: The clinical outcome of craniopharyngioma patients had borderline to below average IQ and poor endocrinal function even before starting RT. We observed an improvement in IQ status 5 years post SCRT.
Multimedia: Website of the week: www.tcwf.org/links/links.htm
Authors: Douglas Carnall
Journal: BMJ (1999)

www.tcwf.org/links/links.htm

Britain has the highest teenage pregnancy rate in western Europe, and things are getting worse rather than better (see p 1321). Matters are worse in the United States, although there are claims that the teenage pregnancy rate is now declining. It's a complex issue, and there is certainly plenty of material out there on the web to down load. This week's featured site is sponsored by a private Californian health foundation and provides a rich set of high quality links to websites of organisations such as the National Campaign to Prevent Teen Pregnancy (www.teenpregnancy.org/fact.htm), the aim of which is to reduce teenage pregnancy by a third by 2005. Its board's eminent members include a former surgeon general of the United States and Whoopi Goldberg, so it must be serious. 

Like most searches on the web, finding information that is not exclusively American in orientation can be a challenge, but the British government's social exclusion unit is doing a fair job of tackling the UK problem. Its web pages live at the heart of the government's website at www.cabinet-office.gov.uk/seu/1998/teenpar.htm, and the main focus of its attentions seems to be a questionnaire designed to identify what government can do to reduce the pregnancy rate. Ministers will need all of their political courage. Teenage pregnancy treads on just about every political corn: from sex education, abortion, and adoption to benefit and housing policies in areas of deprivation, not to mention drugs and alcohol, as I was reminded as I |P`checked my sex IQ|P' at www.plannedparenthood.org/QUIZ/STARTGAME.HTM. 

There is plenty of conservative opinion out there -- see, for example, chapter 82 (out of 140!) of the Pro-life Activist's Encyclopaedia (www.all.org/plae/) -- but most would agree that education is going to be a large part of the answer, and the web has lots of sensible advice directed at teenagers, most notably, Ask Noah (www.noah.cuny.edu/pregnancy/pregnancy.html).