tbuckley/cabot-search huggingface dataset:
Influence of genetic and environmental factors on melanocytic naevi: a lesson from Turner's syndrome
Authors: None Zvulunov, None Wyatt, None Laud, None Esterly
Journal: British Journal of Dermatology (1998)

Females with Turner syndrome (TS) are alleged to have increased numbers of melanocytic naevi. Although a high count of acquired melanocytic naevi (AMN) is one of the major risk factors for melanoma, this malignancy has been reported only rarely in patients with TS. The purpose of this study was to explore the effects of environmental and genetic factors on AMN count and density in TS. AMN count and density in 24 patients with TS treated with growth hormone (GH), 24 GH-treated females with GH deficiency (GHD) and 24 normal females were compared in a cross-sectional study. The average AMN density in TS was 50 naevi/m2 as compared with 18 naevi/m2 in the GHD group and 24 naevi/m2 in normal controls (P = 0.001 and P = 0.004, respectively). Duration of GH therapy did not correlate with AMN count (P = 0.44) or AMN density (P = 0.81). The pattern of distribution of naevi between constantly exposed, intermittently exposed and unexposed skin was similar in all groups. Sun exposure was the major factor that affected the regional AMN densities in the control groups, but not in the TS group. The findings of our study indicate that the effects of environmental factors on AMN count and density may vary among genetically different populations. A review of the literature suggested that melanoma is no more prevalent in TS than in the general population.
Progression and Regression of Atherosclerotic Lesions
Authors: Gérard Helft, Stephen G. Worthley, Valentin Fuster, Zahi A. Fayad, Azfar G. Zaman, Roberto Corti, John T. Fallon, Juan J. Badimon
Journal: Circulation (2002)

Modification or stabilization of atherosclerotic plaques has been proposed as the mechanism responsible for the beneficial clinical effect of lipid-lowering therapies. An imaging modality able to quantify atherosclerotic plaque composition could potentially allow not only the identification of these vulnerable atherosclerotic lesions, but also monitoring of the effects of therapeutic interventions on plaque composition. Our aim was to monitor changes in burden and composition of atherosclerotic plaques in a rabbit model of complex atherosclerosis using serial noninvasive magnetic resonance imaging (MRI).Aortic atherosclerotic lesions were induced in rabbits and the animals randomized to continue an atherogenic diet (atherosclerosis progression) or resume normal chow (atherosclerosis regression) for 6 months. MRI of the aorta was performed at 3 time points in each rabbit, as follows: baseline, after atherosclerosis induction (9 months old), and after atherosclerosis regression or progression (15 months old). Histopathologic correlation with MRI was performed. There was a significant (P<0.0001) reduction in atherosclerotic burden in the regression group, and an increase in the progression group. There was a significant (P<0.001) reduction in the lipidic component of plaques in the regression group, and an increase in the progression group. A small, nonsignificant increase in the fibrotic plaque components was noted in the regression group, but a significant decrease in the fibrotic composition of lesions in the progression group. A significant correlation (P<0.001) was found between MRI and histopathology for atherosclerotic burden and plaque composition.These findings indicate that serial noninvasive MRI can monitor changes in atherosclerotic plaque composition under conditions of atherosclerotic progression and regression.
Pressure-derived fractional collateral blood flow: a primary determinant of left ventricular recovery after reperfused acute myocardial infarction
Authors: Cheol Whan Lee, Seong-Wook Park, Goo-Yeong Cho, Myeong-Ki Hong, Jae-Joong Kim, Duk-Hyun Kang, Jae-Kwan Song, Hyo-Jung Lee, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2000)
"The Air We Breathe"
Authors: J. Berkson
Journal: BMJ (1962)

<b>1822</b> <h3><b>Objectives</b></h3> Cognitive intervention was found to be beneficial in pts with MCI and AD, but the effect of cognitive training on brain metabolism is unexplored. We used FDG-PET to test for metabolic effects of a six month stage-specific cognitive intervention program in pts with aMCI and mild AD. <h3><b>Methods</b></h3> 21 pts with aMCI- and 15 with mild AD syndrome (20 m, 74 yrs) were randomly assigned either to a cognitive intervention group (CIG), receiving weekly sessions of cognitive intervention, or to an active control group (ACG), which met monthly and received pencil and paper exercises for self-study. Groups were matched for syndrome, age-, gender-, APO E4 status, education and degree of cognitive impairment. All pts underwent resting-state FDG-PET and extensive neuropsychological testing at baseline and after 6 months. Normalized FDG-PET images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes and group-by-time interactions (p&lt; 0.001). Changes in global cognitive status were determined by multivariate analyses of covariance with MMSE and ADAS-cog scores as dependent measures (p&lt;0.05). <h3><b>Results</b></h3> There was a trend towards global cognitive improvement in the whole CIG (p=0.06), reaching significance for the aMCI subgroup. ACG showed widespread bilateral declines in FDG uptake in parieto- and occipito- temporal cortices, while CIG showed discrete decline only in left inferior occipital gyrus. Group by time analyses revealed for the whole CIG attenuation of metabolic decline in right inferior-/ middle temporal gyrus, and right middle frontal gyrus, while for the aMCI subgroup attenuation effects were strongest and occurred in left superior temporal gyrus and anterior cingulate gyrus. <h3><b>Conclusions</b></h3> A six-month stage-specific cognitive intervention program in pts with aMCI and mild AD imparted cognitive benefits, which could be linked for the first time to an attenuated metabolic decline in regions typically affected by neurodegenerative AD
Obstetrician suspended after research inquiry
Authors: C. Court, L. Dillner
Journal: BMJ (1994)

A consultant obstetrician has been suspended from duty at St George's Hospital in south London after an inquiry into the scientific validity of two research papers. The consultant in question, Mr Malcolm Pearce, was the first author of the papers, both published in August in the British Journal of Obstetrics and Gynaecology. He has also been suspended from his honorary senior lectureship at St George's Hospital Medical School.

The two papers are a case report entitled “Term delivery after intrauterine relocation of an ectopic pregnancy” and a paper entitled “Randomised controlled trial of the use of human chorionic gonadotrophin in recurrent miscarriage associated with polycystic ovaries.”

The case report, concerning a 29 year old African woman who had previously had two ectopic pregnancies, described a procedure whereby the fetus in her third ectopic pregnancy was removed and replaced in her …
Decreased cytokine response profiles as a predictor of allergic sensitization
Authors: C.J. Tisler, Z. Li, D. DaSilva, K. Anklum, K. Roberg, K. Carlson-Dakes, B. Anderson, R. Gangnon, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2003)
The 1995 Health Policy Debate
Authors: Drew Altman
Journal: JAMA (1995)

Three big problems brought us the health system reform debate, and with the collapse of this year's historic reform effort, all three are destined to get worse. The number of uninsured will continue to grow, as it did by more than 1 million between 1992 and 1993.<sup>1</sup>Middle-class health insurance problems and insecurities will also grow, as more and more Americans find their benefits cut and their out-of-pocket costs increased, their insurance dropped, or their choices constrained.<sup>2,3</sup>And despite the recent moderation in price increases in health, even the most optimistic forecasts see health care spending rising to levels that will consume an ever-larger share of the federal budget.<sup>4</sup> These realities will force renewed debate about health system reform in 1995. However, the starting point will not be the sweeping proposals of last year, but more likely the incremental reform plans we saw considered as Congress adjourned.
Thickness Unto Death?
Authors: Jeffrey J. Sacks
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Two generic scoring systems are commonly used to quantitatively assess the severity of illness of intensive care unit (ICU) patients. These scoring systems are based on either physiological or therapeutic indexes.<sup>1-3</sup>As part of a retrospective study of ICU patients, we assessed their illness severity using both systems. For each of 302 patients (103 with cardiac arrest, 199 with no cardiac arrest), we calculated a patient classification system (PCS) score. This score is used by some hospitals to measure the amount of nursing care required per patient and is a modification of a therapeutic intervention scoring system.<sup>1</sup>To validate the PCS score, a stratified random sample of 62 patients (26 with cardiac arrest, 36 with no cardiac arrest) was scored with the APACHE II, a physiologically based illness scoring system that has been shown to be a valid predictor of risk of death in ICU
Nurses join the BMA over local performance pay
Authors: L Beecham
Journal: BMJ (1994)

The secretary of the Royal College of Nursing and the chairman of the BMA council have signed a joint letter to their members urging them to make known their views on local performance pay. Ms Christine Hancock and Dr Sandy Macara say that “a patchwork of locally determined pay proposals is no substitute for a national pay award.” They believe that there would be a deterioration in the quality of patient care and that the financially successful hospitals would be able to attract the best staff.

They point out that independent evidence shows that performance related pay demotivates staff, undermines morale, and is unfair; that local performance pay will not lead to higher NHS standards; and that the review body system is fair, cost effective, and has succeeded in preventing disputes.

The letter urges doctors and nurses to speak publicly in local newspapers and other media, or through a press conference, a public meeting, or a joint letter; to make their views known to their member of parliament; and to arrange a joint meeting with the chairperson of the local trust.

* The National Association of Health Authorities and Trusts says that it regrets the statement by the BMA and RCN. “If NHS trusts are to improve their efficiency and introduce more flexible working arrangements it is essential that they manage their pay determination and reward locally,” the association's director, Mr Philip Hunt, said. And the NHS Trust Federation hopes that the review bodies will announce a zero or …
Pulmonary Capillary Endothelium-Bound Angiotensin-Converting Enzyme Activity in Acute Lung Injury
Authors: Stylianos E. Orfanos, Apostolos Armaganidis, Constantinos Glynos, Ekaterini Psevdi, Panagiotis Kaltsas, Paulina Sarafidou, John D. Catravas, Urania G. Dafni, David Langleben, Charis Roussos
Journal: Circulation (2000)

Background —Pulmonary capillary endothelium-bound (PCEB) angiotensin-converting ectoenzyme (ACE) activity alteration is an early, sensitive, and quantifiable lung injury index in animal models. We hypothesized that (1) PCEB-ACE alterations can be found in patients with acute lung injury (ALI) and (2) PCEB-ACE activity correlates with the severity of lung injury and may be used as a quantifiable marker of the underlying pulmonary capillary endothelial dysfunction. Methods and Results —Applying indicator-dilution techniques, we measured single-pass transpulmonary hydrolysis of the synthetic ACE substrate 3 H-benzoyl-Phe-Ala-Pro (BPAP) in 33 mechanically ventilated, critically ill patients with a lung injury score (LIS) ranging from 0 (no lung injury) to 3.7 (severe lung injury) and calculated the kinetic parameter A max /K m . Both parameters decreased early during the ALI continuum and were inversely related to APACHE II score and LIS. Hydrolysis decreased with increasing cardiac output (CO), whereas 2 different patterns were observed between CO and A max /K m . Conclusions —PCEB-ACE activity decreases early during ALI, correlates with the clinical severity of both the lung injury and the underlying disease, and may be used as a quantifiable marker of underlying pulmonary capillary endothelial dysfunction.
Chest pain and ST elevation
Authors: S. P. Page, A. Archbold, D. J. Abrams
Journal: BMJ (2012)

A 53 year old Vietnamese man developed chest pain at rest and dialled the emergency services. The ambulance service identified ST elevation on 12 lead electrocardiography (ECG) and according to local protocol brought him direct to our cardiac centre with a suspected ST elevation myocardial infarction. On arrival he reported a three hour history of central chest pain without radiation or associated symptoms. He was a current smoker but had no other risk factors for coronary artery disease. Examination was unremarkable and an ECG was performed on arrival. In lead V1 there was 2 mm of coved J point elevation, with an inverted T wave. In V2 there was 4 mm of J point elevation, with a saddle shaped ST segment and an upright T wave. In V3 the J point, ST segment, and T wave were within normal limits. He underwent immediate coronary angiography, which showed mild atheroma in the left anterior descending artery, but no obstructive lesions, and transthoracic echocardiography showed normal cardiac structure with good biventricular function.

Overnight he developed a productive cough associated with a fever. Serial ECGs were recorded while he was febrile and showed 3 mm of coved J point elevation in lead V1 and 5 mm of coved J point elevation in V2, with associated T wave inversion.

On further questioning he admitted to a history of well tolerated intermittent palpitations of up to an hour’s duration. His father had died suddenly and unexpectedly by falling from a bridge, but …
Prostaglandins and the Hypercalcemia of Cancer
Authors: Lawrence G. Raisz
Journal: New England Journal of Medicine (1973)

Since prostaglandins are the glamour compounds of the 70's and cancer has been designated as the target for medical research in this decade, their conjunction seemed inevitable. It is surprising, nevertheless, that a meeting should have occurred in the generally neglected field of the hypercalcemia of cancer. Hypercalcemia is a common complication of many neoplasms, some of which show direct bone involvement whereas others do not. In either case, we usually do not know the mechanism of the hypercalcemia. Only a few tumors have been shown to secrete immunoreactive parathyroid hormone. In this issue of the Journal Powell and his . . .
Outcomes in the treatment of thrombotic thrombocytopenic purpura with splenectomy: A retrospective cohort study
Authors: Ubaldo Martinez Outschoorn, Andres Ferber
Journal: American Journal of Hematology (2006)

Abstract The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE), but the role of splenectomy is still undefined. The records of all patients with TTP at a single center over a 20‐year period were retrospectively reviewed. Response to plasma exchange was determined. The outcome of patients treated with splenectomy in the setting of TTP was evaluated. Sixty‐one patients had been treated for TTP. Thirty‐nine patients (64%) achieved complete remission (CR) with PE, nineteen (31%) of these achieving sustained CR and seventeen (28%) with relapsed TTP. Twenty patients (33%) had PE refractory TTP and two patients (3%) had PE dependent TTP. During this time period, 10 patients (16%) underwent splenectomy, four patients (7%) for PE dependent TTP, three (5%) for relapsed TTP, and three (5%) for refractory TTP. All of the patients achieved CR after splenectomy. Two patients who had undergone splenectomy had subsequent relapses, both with previously relapsed TTP. In relapsed patients the relapse rate after splenectomy was 0.27 events per patient year compared to 0.6 events per patient year before splenectomy. Median follow‐up after splenectomy was 19 months (range 0.13–90 months). In conclusion, relapses in TTP can be managed successfully with additional PE or with splenectomy. PE dependent or refractory TTP can be successfully treated with splenectomy. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
FGFR1/3 Tyrosine Kinase Fusions Define a Unique Molecular Subtype of Non–Small Cell Lung Cancer
Authors: Rui Wang, Lei Wang, Yuan Li, Haichuan Hu, Lei Shen, Xuxia Shen, Yunjian Pan, Ting Ye, Yang Zhang, Xiaoyang Luo, Yiliang Zhang, Bin Pan, Bin Li, Hang Li, Jie Zhang, William Pao, Hongbin Ji, Yihua Sun, Haiquan Chen
Journal: Clinical Cancer Research (2014)

The fibroblast growth factor receptor (FGFR)-3 fusion genes have been recently demonstrated in a subset of non-small cell lung cancer (NSCLC). To aid in identification and treatment of these patients, we examined the frequency, clinicopathologic characteristics, and treatment outcomes of patients who had NSCLC with or without FGFR fusions.Fourteen known FGFR fusion variants, including FGFR1, FGFR2, and FGFR3, were detected by RT-PCR and verified by direct sequencing in 1,328 patients with NSCLC. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, and ROS1. Clinical characteristics, including age, sex, smoking status, stage, subtypes of lung adenocarcinoma, relapse-free survival, and overall survival, were collected.Of 1,328 tumors screened, two (0.2%) were BAG4-FGFR1 fusion and 15 (1.1%) were FGFR3-TACC3 fusion. Six of 1,016 patients with lung adenocarcinoma were FGFR3-TACC3 fusions and 11 of 312 lung squamous cell carcinoma harbored BAG4-FGFR1 or FGFR3-TACC3 fusions. Compared with the FGFR fusion-negative group, patients with FGFR fusions were more likely to be smokers (94.1%, 16 of 17 patients, P < 0.001), significantly associated with larger tumor (>3 cm; 88.2%, 15 of 17 patients, P < 0.001) and with a tendency to be more poorly differentiated (53.9%, nine of 17 patients, P = 0.095).FGFR fusions define a molecular subset of NSCLC with distinct clinical characteristics. FGFR is a druggable target and patients with FGFR fusions may benefit from FGFR-targeted therapy, which needs further clinical investigation.
Elevated Plasma Lipoprotein(a) and Coronary Heart Disease in Men Aged 55 Years and Younger
Authors: Andrew G. Bostom
Journal: JAMA (1996)

<h3>Objective.</h3> —To establish whether elevated lipoprotein(a) [Lp(a)], detected as a sinking pre-β-lipoportein band on electrophoresis of fresh plasma, is an independent risk factor for the development of premature coronary heart disease (CHD) in men. <h3>Design and Setting.</h3> —Prospective study of the Framingham offspring cohort. <h3>Participants.</h3> —A total of 2191 men aged 20 to 54 years old who were free of cardiovascular disease when they were examined between 1971 and 1975. <h3>Main Outcome Measures.</h3> —Incident CHD (myocardial infarction, coronary insufficiency, angina pectoris, or sudden cardiac death) occurring by age 55 years. <h3>Results.</h3> —After a median follow-up of 15.4 years, there were 129 CHD events. The relative risk (RR) estimates (with 95% confidence intervals [Cls]) for premature CHD derived from a proportional hazards model that included age, body mass index, and the dichotomized risk factor covariables elevated plasma Lp(a) level, total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, high-density lipoprotein (HDL) level less than 0.9 mmol/L (35 mg/dL), smoking, glucose intolerance, and hypertension were as follows: elevated Lp(a) level, RR, 1.9 (95% CI, 1.2-2.9), prevalence, 11.3%; total cholesterol level of 6.2 mmol/L or more, RR, 1.8 (95% CI, 1.2-2.7), prevalence, 14.3%; HDL level of less than 0.9 mmol/L, RR, 1.8 (95% CI, 1.2-2.6), prevalence, 19.2%; smoking, RR, 3.6 (95% CI, 2.2-5.5), prevalence, 46.7%; glucose intolerance, RR, 2.7 (95% CI, 1.4-5.3), prevalence, 2.6%; hypertension, RR, 1.2 (95% CI, 0.8-1.8), prevalence, 26.3%. <h3>Conclusions.</h3> —Elevated plasma Lp(a) is an independent risk factor for the development of premature CHD in men, comparable in magnitude and prevalence (ie, attributable risk) to a total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, or an HDL level less than 0.9 mmol/L (35 mg/dL).
Long QT Syndrome in Adults
Authors: Andrew J. Sauer, Arthur J. Moss, Scott McNitt, Derick R. Peterson, Wojciech Zareba, Jennifer L. Robinson, Ming Qi, Ilan Goldenberg, Jenny B. Hobbs, Michael J. Ackerman, Jesaia Benhorin, W. Jackson Hall, Elizabeth S. Kaufman, Emanuela H. Locati, Carlo Napolitano, Silvia G. Priori, Peter J. Schwartz, Jeffrey A. Towbin, G. Michael Vincent, Li Zhang
Journal: Journal of the American College of Cardiology (2007)
Inhibition of Proliferation and Induction of Apoptosis by 25-Hydroxyvitamin D3-3β-(2)-Bromoacetate, a Nontoxic and Vitamin D Receptor-Alkylating Analog of 25-Hydroxyvitamin D3 in Prostate Cancer Cells
Authors: Narasimha Swamy, Tai C. Chen, Sara Peleg, Puneet Dhawan, Sylvia Christakos, LaMonica V. Stewart, Nancy L. Weigel, Rajendra G. Mehta, Michael F. Holick, Rahul Ray
Journal: Clinical Cancer Research (2004)

Abstract The 25-hydroxyvitamin D3 (25-OH-D3) is a nontoxic and low-affinity vitamin D receptor (VDR)-binding metabolic precursor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We hypothesized that covalent attachment of a 25-OH-D3 analog to the hormone-binding pocket of VDR might convert the latter into transcriptionally active holo-form, making 25-OH-D3 biologically active. Furthermore, it might be possible to translate the nontoxic nature of 25-OH-D3 into its analog. We showed earlier that 25-hydroxyvitamin D3-3-bromoacetate (25-OH-D3-3-BE) alkylated the hormone-binding pocket of VDR. In this communication we describe that 10−6 mol/L of 25-OH-D3-3-BE inhibited the growth of keratinocytes, LNCaP, and LAPC-4 androgen-sensitive and PC-3 and DU145 androgen-refractory prostate cancer cells, and PZ-HPV-7 immortalized normal prostate cells with similar or stronger efficacy as 1,25(OH)2D3. But its effect was strongest in LNCaP, PC-3, LAPC-4, and DU145 cells. Furthermore, 25-OH-D3-3-BE was toxic to these prostate cancer cells and caused these cells to undergo apoptosis as shown by DNA-fragmentation and caspase-activation assays. In a reporter assay with COS-7 cells, transfected with a 1α,25-dihydroxyvitamin D3-24-hydroxylase (24-OHase)-construct and VDR-expression vector, 25-OH-D3-3-BE induced 24-OHase promoter activity. In a “pull down assay” with PC-3 cells, 25-OH-D3-3-BE induced strong interaction between VDR and general transcription factors, retinoid X receptor, and GRIP-1. Collectively, these results strongly suggested that the cellular effects of 25-OH-D3-3-BE were manifested via 1,25(OH)2D3/VDR signaling pathway. A toxicity study in CD-1 mice showed that 166 μg/kg of 25-OH-D3-3-BE did not raise serum-calcium beyond vehicle control. Collectively, these results strongly suggested that 25-OH-D3-3-BE has a strong potential as a therapeutic agent for androgen-sensitive and androgen-refractory prostate cancer.