tbuckley/cabot-search huggingface dataset:
Consultants and their future
Authors: P. D Welsby
Journal: BMJ (1981)

<h3>Introduction/Background</h3> Ovarian cancer is the sixth most common cancer in women in the UK and a leading cause of death from gynaecological cancers, with effective screening and early detection remaining elusive. Vibrational spectroscopy is a rapid, low-cost, non-invasive analytical tool with the potential to classify benign and malignant pathologies according to their biochemical composition. We report on findings of infrared (IR) spectroscopy of ascitic fluid from women with or without ovarian cancer which, to our knowledge, has been conducted for the first time. <h3>Methodology</h3> Attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy was conducted on ascites collected from 20 patients with benign gynaecological pathology, 5 patients with borderline ovarian tumours and 20 ovarian cancer patients. Ten spectra were acquired from each sample. The obtained spectra were pre-processed by cutting the fingerprint region and applying the Savitzky-Golay 2nd derivative and vector normalisation. Classification was conducted by partial least squares discriminant analysis (PLS-DA) with 9 latent variables (94% explained variance) and Support Vector Machines (SVM) algorithm. <h3>Results</h3> Fitting accuracy for discrimination of the 3 classes with PLS-DA was 88% (training set with 70% of samples). When the model was fed with external test samples (30% of samples) the prediction accuracy was 85%. Sensitivity was 0.91, 0.80 and 0.79 for benign, borderline and cancer categories, while specificity was 0.85, 0.96 and 0.93, respectively. However, with SVM, accuracies for fitting and external test samples discrimination were 100%. Additionally, obtained sensitivities and specificities were 100% for the 3 different classes, confirming a better diagnosis response using SVM. <h3>Conclusion</h3> ATR-FTIR spectroscopy demonstrates excellent potential for classifying ovarian cancer and non-cancerous gynaecological conditions in ascitic fluid. <h3>Disclosure</h3> Nothing to disclose.
IDIOSYNCRASY TO HEXYLRESORCINOL
Authors: Carl W. Walter
Journal: JAMA (1935)

The unusual severity of the manifestation of an acquired sensitivity to hexylresorcinol warrants the report of this case. Idiosyncrasy to hexylresorcinol has been described by Templeton and Lunsford<sup>1</sup>and by Cummer.<sup>2</sup> <h3>REPORT OF CASE</h3><h3>History.</h3> —An American woman, aged 57, a housewife, scratched the dorsum of her left hand on a jagged piece of glass protruding from the frame of a broken window. A wet dressing of hexylresorcinol solution was applied for approximately thirty minutes, and the injury was dismissed as trivial. Twenty-four hours later the area moistened by the dressing began to itch and burn, and the skin about the scratch became red and swollen. Vesicles formed in the center of the lesion during the following day. As the lesion spread, the vesicles coalesced to form large blebs. Itching and burning sensations were supplanted by a dull throbbing ache. Three days following the original injury
Pfizer closes Kent plant as it trims research spending by $1bn a year
Authors: N. Hawkes
Journal: BMJ (2011)

Pfizer, the world’s biggest selling drug company, has announced plans to close its research and development plant at Sandwich in Kent, with the loss of 2400 jobs.

The closure is part of a plan to trim research spending from over $8bn (£4.9bn; €5.8bn) a year to less than $7bn and to focus on areas that offer the greatest promise, such as cancer and vaccines. Like other big drug companies Pfizer is responding to the declining productivity of traditional drug research and hoping to acquire new products by buying up small biotech companies.

The immediate aim is to meet earnings targets in 2012, which are threatened by two major brands, Lipitor (atorvastatin) and Viagra (sildenafil), coming off patent in the United States. Lipitor, acquired …
689. Therapeutic Angiogenesis for Prefabrication of Ischemic Flaps with Multiple Growth Factor Gene Transfers: A Study in a Rat Model
Authors: Paul Y. Liu, Kan Liu, Xiao Tian Wang, Kimberly M. Rieger-Christ, Jin Bo Tang, Ian C. Summerhayes
Journal: Molecular Therapy (2005)

Top of pageAbstract
Purpose: Necrosis of transferred flaps is a major problem in reconstructive surgery and is primarily due to insufficient angiogenesis in the transferred flaps. Enhancement of angiogenesis by flap prefabrication has been a focus of investigations and remains a challenge to both researchers and surgeons. The objective of this study was to investigate the efficacy of combination gene therapy with multiple growth factor cDNAs to enhance survival of ischemic skin in a rat model.

Materials and Methods: Sixty Sprague-Dawley rats were divided into 6 groups. Varying combinations of VEGF-, PDGF-, and bFGF-plasmids were injected to prefabricate the flaps. Random skin flaps were raised on the dorsal aspect of rats following prefabrication with growth factor cDNAs. Flap viability was determined by measurement of percentage area of survival. The efficacy of gene therapy was evaluated by flap survival and neovascularization of representative histologic sections stained immunohistologically with antibody to von Willebrand Factor.

Results: The VEGF plus bFGF cDNAs enhanced the viability of the flap and neovascularization most effectively; the flap survival area was 64.3 +//0 8.7 % after transfer of these 2 growth factor genes. Addition of PDGF cDNA is deleterious to the effects of combined VEGF and bFGF, leading to a significant decrease in flap viability (44.9 +//0 2.7 %). Viability of the flaps with combined VEGF and bFGF cDNA transfer was significantly greater than that of the flaps with VEGF transfer alone (57.6 +//0 5.2 %) or sham plasmid control (52.3 +//0 5.0 %).

Discussion: Transfer of a single angiogenic growth factor gene, VEGF or PDGF, significantly improved viability of ischemic flaps in previous studies of the authors' and other groups. Transfer of multiple genes encoding angiogenic growth factors to ischemic flaps has not been reported. An important and intriguing finding of our current study is that combined transfer of 2 growth factor genes (VEGF and bFGF) significantly improved flap survival, but in contrast 3 growth factor genes (VEGF, bFGF, and PDGF) drastically worsened the viability of the flap. Transfer of 3 growth factor genes to ischemic flaps appears not advantageous because of interactions between these genes or increases in production of multiple growth factors may not lead to functional improvement of vascular supplies to the flaps and decreases the effectiveness of angiogenesis.

Conclusions: Combined transfer of VEGF and bFGF cDNA is the most effective combination of multiple growth factor genes to improve flap viability in this model. Simultaneous transfer of 3 growth factor genes (VEGF, PDGF, and bFGF) is deleterious to flap survival.
Asthma in the Elderly
Authors: H. Y. Lee, T. B. Stretton
Journal: BMJ (1972)

Fifteen patients who developed asthma after the age of 60 years are reported. Attention is drawn to apparent difficulties of diagnosis in this age group. A history of chronic bronchitis is common, and a change in symptoms, especially the abrupt onset of increased breathlessness, wheezing, and paroxysmal nocturnal dyspnoea, should arouse suspicion of the development of asthma. A past or family history of allergy is confirmatory evidence, as is the presence of blood or sputum eosinophilia. Retrosternal pain is not uncommon, and angina pectoris or left ventricular failure must be excluded. Chest radiographs showed changes consistent with old quiescent tuberculosis in five patients; careful follow-up is therefore essential as asthma in this age group often requires steroid therapy.
Synergistic Polymorphisms of β<sub>1</sub>- and α<sub>2C</sub>-Adrenergic Receptors and the Risk of Congestive Heart Failure
Authors: Kersten M. Small, Lynne E. Wagoner, Albert M. Levin, Sharon L.R. Kardia, Stephen B. Liggett
Journal: New England Journal of Medicine (2002)

Sustained cardiac adrenergic stimulation has been implicated in the development and progression of heart failure. Release of norepinephrine is controlled by negative feedback from presynaptic alpha2-adrenergic receptors, and the targets of the released norepinephrine on myocytes are beta1-adrenergic receptors. In transfected cells, a polymorphic alpha2C-adrenergic receptor (alpha2CDel322-325) has decreased function, and a variant of the beta1-adrenergic receptor (beta1Arg389) has increased function. We hypothesized that this combination of receptor variants, which results in increased synaptic norepinephrine release and enhanced receptor function at the myocyte, would predispose persons to heart failure.Genotyping at these loci was performed in 159 patients with heart failure and 189 controls. Logistic-regression methods were used to determine the potential effect of each genotype and the interaction between them on the risk of heart failure.Among black subjects, the adjusted odds ratio for heart failure among persons who were homozygous for alpha2CDel322-325 as compared with those with the other alpha2C-adrenergic receptor genotypes was 5.65 (95 percent confidence interval, 2.67 to 11.95; P<0.001). There was no increase in risk with beta1Arg389 alone. However, there was a marked increase in the risk of heart failure among persons who were homozygous for both variants (adjusted odds ratio, 10.11; 95 percent confidence interval, 2.11 to 48.53; P=0.004). The patients with heart failure did not differ from the controls in the frequencies of nine short tandem-repeat alleles. Among white subjects, there were too few who were homozygous for both polymorphisms to allow an adequate assessment of risk.The alpha2CDel322-325 and beta1Arg389 receptors act synergistically to increase the risk of heart failure in blacks. Genotyping at these two loci may be a useful approach for identification of persons at risk for heart failure or its progression, who may be candidates for early preventive measures.
Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin induced enterocolitis in genetically susceptible Lewis rats
Authors: A Stadnicki, R B Sartor, R Janardham, I Stadnicka, A A Adam, C Blais, R W Colman
Journal: Gut (1998)

Background —The plasma kallikrein-kinin (K-K) system is activated in acute and chronic relapsing intestinal inflammation induced in Lewis rats by intramural injection of exogenous bacterial components. Aims —To determine whether this effect is model specific, K-K system activation was investigated in a modified indomethacin induced enterocolitis model, as well as bradykinin 2 (B2) receptor distribution in the normal and acutely inflamed intestine. Methods —Lewis rats injected with daily sublethal doses of indomethacin for two days developed acute (two days) and chronic (14 days) intestinal inflammation. Plasma prekallikrein (amidolytic), high molecular weight kininogen (HK, coagulant) and cleavage of HK (western blot) were assayed to detect K-K activation. Results —Liver and spleen weights were significantly higher, and body weights and haematocrit values were significantly lower in the indomethacin group than in the control group. During both acute and chronic phases, rats displayed K-K system activation manifested by a significant decrease in plasma prekallikrein and HK functional levels, and by HK cleavage. Plasma T kininogen (a major acute phase protein) was significantly elevated. B2 receptors were identified in both normal and inflammatory intestine with more prominent specific immunohistochemical staining in the acutely inflamed tissue. Conclusions —K-K system activation occurs in association with both acute and chronic phases of intestinal injury, regardless of the triggering agent, suggesting that activation of this system is integrally involved in intestinal inflammation in genetically susceptible hosts. Localisation of B2 receptors across intestinal layers provides a structural basis for the kinin function in the intestine.
Cytokine gene polymorphisms in Chinese patients with psoriasis
Authors: Y.T. Chang, C.T. Chou, C.W. Yu, M.W. Lin, Y.M. Shiao, C.C. Chen, C.H. Huang, D.D. Lee, H.N. Liu, W.J. Wang, S.F. Tsai
Journal: British Journal of Dermatology (2007)

Previous studies have shown that cytokine gene polymorphisms may confer susceptibility to psoriasis.To determine whether genetic polymorphisms of the cytokine genes might influence the development of psoriasis in Chinese patients in Taiwan.DNA samples were obtained from 170 patients with psoriasis vulgaris (PV), 102 patients with psoriatic arthritis (PsA) and 210 control subjects. Using direct sequencing and microsatellite genotyping, we examined 28 polymorphisms in 11 cytokine genes including the interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-8, IL-10, IL-12B, IL-13, tumour necrosis factor (TNF)-alpha, TNF-beta and interferon-gamma genes. Genotypes of HLA-Cw*0602, killer cell immunoglobulin-like receptor (KIR) genes and major histocompatibility complex class I chain-related gene A (MICA) were also determined in patients with PsA.The patients with PV were more likely to carry the +4496G allele of the IL-12B gene (59.4% vs. 49.3%, P = 0.0067, P(c) = 0.033). However, no significantly different allelic and genotypic distributions of the other analysed genes including IL-1beta, TNF-alpha, TNF-beta, KIR genes and MICA were found between the PV/PsA patients and controls. Moreover, no association was observed with disease onset, gender, peripheral arthritis or joint erosion. With regards to HLA-Cw*0602, its allele frequency was significantly increased in patients with early-onset PV (25.3% vs. 4.8%, P < 10(-7)), but not in patients with PsA.The IL-12B gene polymorphism conferred a risk for PV in our Chinese population, although the effect was more minor than that of HLA-Cw*0602. Cw*0602, KIR2DS1/S2 and MICA-A9 were unlikely to be risk alleles in our patients with PsA. The other analysed genetic polymorphisms of cytokine genes do not appear to be associated with susceptibility to PV and PsA in Chinese patients in Taiwan.
Diagnostic accuracy of<sup>18</sup>F-methylcholine positron emission tomography/computed tomography for intra- and extrahepatic hepatocellular carcinoma
Authors: Matthanja Bieze, Heinz-Josef Klümpen, Joanne Verheij, Ulrich Beuers, Saffire S.K.S. Phoa, Thomas M. van Gulik, Roelof J. Bennink
Journal: Hepatology (2013)

Diagnosis of hepatocellular carcinoma (HCC) primarily involves imaging. The aim of this study was to assess the accuracy of (18) F-fluorocholine ((18) F-FCH) positron emission tomography (PET) for detection of HCC and evaluation of extent of disease. Patients with HCC >1 cm were included between 2009 and July 2011, and follow-up closed in February 2013. Diagnosis was based on American Association for the Study of Liver Diseases criteria, and all patients underwent (18) F-FCH PET/computed tomography (CT) at baseline before treatment, 6 underwent a second PET/CT posttreatment, and 1 a third during follow-up. Whole-body PET and low-dose CT imaging were performed 15 minutes after (18) F-FCH injection. Evaluation of imaging was done with standardized uptake value (SUV) ratios: SUV maximum of the lesion divided by the SUV mean of surrounding tissue. Statistical analyses included descriptive analyses, receiver operating characteristic curve, McNemar's test, and Kaplan-Meier's test at 5% level of significance. Twenty-nine patients revealed 53 intrahepatic lesions. In 48 of 53 lesions, (18) F-FCH PET was positive (SUVratio , 1.95 ± 0.66; sensitivity, 88%; specificity, 100%). PET/CT showed uptake in 18 extrahepatic lesions and no uptake in 3 lesions affirmed non-HCC lesions; all lesions were confirmed with additional investigation (accuracy, 100%). In 17 of 29 patients, additional lesions were found on PET/CT imaging, with implications for treatment in 15 patients. Posttreatment PET/CT showed identical results, compared with standard treatment evaluation.This study shows additional value of (18) F-FCH PET/CT for patients with HCC. (18) F-FCH PET/CT has implications for staging, management, and treatment evaluation because of accurate assessment of extrahepatic disease.
PORRO-CÆ:SARIAN SECTION.Read in the Section of Obstetrics and Diseases of Women, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: J. H. CARSTENS
Journal: JAMA (1893)

Having had the pleasure of reporting a successful Porro-Cœsarian section in the<i>American Journal of Obstetrics</i>last year, it is peculiar that I should be able to report another case within six months. The second case is as follows: Mrs. S. is 23 years old; her mother died of pneumonia at the age of 55; her father is living and healthy; she has two brothers and three sisters living; one of the latter had six children, the other had five. They were always delivered by a midwife. Mrs. S. is of German parentage, but was born in this country. In the fall of 1891, I was called upon by Dr. W. J. Brand to help him deliver her. She had been under the care of a midwife for twenty-four hours when he was called, and failed to deliver her with forceps. As the child was dead the only thing to
A Combined Computational and Experimental Study on the Structure-Regulation Relationships of Putative Mammalian DNA Replication Initiator GINS
Authors: Reiko Hayashi, Takako Arauchi, Moe Tategu, Yuya Goto, Kenichi Yoshida
Journal: Genomics Proteomics & Bioinformatics (2006)

Abstract GINS, a heterotetramer of SLD5, PSF1, PSF2, and PSF3 proteins, is an emerging chromatin factor recognized to be involved in the initiation and elongation step of DNA replication. Although the yeast and Xenopus GINS genes are well documented, their orthologous genes in higher eukaryotes are not fully characterized. In this study, we report the genomic structure and transcriptional regulation of mammalian GINS genes. Serum stimulation increased the GINS mRNA levels in human cells. Reporter gene assay using putative GINS promoter sequences revealed that the expression of mammalian GINS is regulated by 17β-Estradiol-stimulated estrogen receptor α, and human PSF3 acts as a gene responsive to transcription factor E2F1. The goal of this study is to present the current data so as to encourage further work in the field of GINS gene regulation and functions in mammalian cells.
Regarding “Sweet Time Unafflicted”
Authors: David R. Macdonald
Journal: Journal of Clinical Oncology (2003)

To the Editor: I disagree with Alberts et al 1 when they contend that intraperitoneal chemotherapy should be considered standard treatment for stage III ovarian cancer.The editorialists seem surprised that this treatment approach has not received widespread acceptance despite "three positive phase III trials."However, the Gynecologic Oncology Group (GOG) study, GOG-172, 2 has been reported only in abstract form without mature survival data, and the GOG-114 3 showed marginally significant survival improvement using a regimen that the authors themselves rejected as too toxic for further study.The earlier Intergroup trial 4 is equally problematic, as the survival difference was small, with about a 4% difference in 6-year overall survival, overlapping confidence intervals for median survival (42% to 54% with and 35% to 45% without intraperitoneal treatment), and two treatment-related deaths in the intraperitoneal chemotherapy group.In addition, there was no treatment benefit seen in that study for the subgroup of patients with minimal residual disease.This argues against the editorialists' claim that the benefit of intraperitoneal chemotherapy is based on a "well-established pharmacologic principle."Furthermore, the Intergroup study was conducted before the availability of taxanes, and therefore, the control group received only cyclophosphamide and cisplatin.It remains to be seen whether the small improvement in survival with intraperitoneal chemotherapy can be more easily obtained with the use of better systemic therapy.Before we subject all patients with optimally debulked stage III ovarian cancer to the inconvenience and toxicity of intraperitoneal therapy, we must first demonstrate that it is worth the bother.It would seem prudent to await the publication of mature survival and toxicity data from the GOG-172 study.
What's Wrong with Radiology
Authors: Richard S. Heilman
Journal: New England Journal of Medicine (1982)

One of the remarkable paradoxes in contemporary American medicine is the presence of a vague but definite malaise surrounding radiologic diagnosis at a time of unparalleled excitement and accomplishment in the development of imaging hardware and techniques. Diagnostic data of previously unimaginable, virtually anatomic precision are now widely available. Yet the satisfaction that might be expected among clinicians and radiologists as a result of the increasingly elegant information made possible by computed tomography, ultrasound, nuclear medicine, and digital subtraction techniques is nowhere apparent. In fact, a fairly solid case could be made for the existence of an inverse relation between . . .
Blood pressure and myocardial infarction Low blood pressure can be hazardous
Authors: J M Cruickshank, J Cooer, T S Warrender
Journal: BMJ (1994)

EDITOR, - The study of Ulf Lindblad and colleagues highlights a high risk group of hypertensive patients with evidence on electrocardiography of ischaemia or left ventricular hypertrophy, or both, who experience a greater number of first myocardial infarctions (than those with normal electrocardiograms) if their diastolic blood pressure is lowered to below 95 mm Hg.1 These new data supplement the findings of the Framingham study, which showed no J curve relation between diastolic blood pressure and deaths from coronary heart disease for those without coronary heart disease or left ventricular hypertrophy. By contrast, those with either coronary heart disease or left ventricular hypertrophy showed a J point in the high 70s of diastolic blood pressure and those with combined coronary heart disease and left ventricular hypertrophy had a J point shifted to the right at pressures of 85-89 mm Hg.

Lindblad and colleagues indicate that left ventricular hypertrophy is associated …
A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection
Authors: Steve Hoffmann, Christian Otto, Gero Doose, Andrea Tanzer, David Langenberger, Sabina Christ, Manfred Kunz, Lesca M Holdt, Daniel Teupser, Jörg Hackermüller, Peter F Stadler
Journal: Genome biology (2014)

Abstract Numerous high-throughput sequencing studies have focused on detecting conventionally spliced mRNAs in RNA-seq data. However, non-standard RNAs arising through gene fusion, circularization or trans-splicing are often neglected. We introduce a novel, unbiased algorithm to detect splice junctions from single-end cDNA sequences. In contrast to other methods, our approach accommodates multi-junction structures. Our method compares favorably with competing tools for conventionally spliced mRNAs and, with a gain of up to 40% of recall, systematically outperforms them on reads with multiple splits, trans-splicing and circular products. The algorithm is integrated into our mapping tool ( http://www.bioinf.uni-leipzig.de/Software/segemehl/ ).