tbuckley/cabot-search huggingface dataset:
Increased late sodium current contributes to long QT-related arrhythmia susceptibility in female mice
Authors: John S. Lowe, Dina Myers Stroud, Tao Yang, Lynn Hall, Thomas C. Atack, Dan M. Roden
Journal: Cardiovascular Research (2012)

AimsFemale gender is a risk factor for long QT-related arrhythmias, but the underlying mechanisms remain uncertain.Here, we tested the hypothesis that gender-dependent function of the post-depolarization 'late' sodium current (I Na-L ) contributes. Methods and resultsStudies were conducted in mice in which the canonical cardiac sodium channel Scn5a locus was disrupted, and expression of human wild-type SCN5A cDNA substituted.Baseline QT intervals were similar in male and female mice, but exposure to the sodium channel opener anemone toxin ATX-II elicited polymorphic ventricular tachycardia in 0/9 males vs. 6/9 females.Ventricular I Na-L and action potential durations were increased in myocytes isolated from female mice compared with those from males before and especially after treatment with ATX-II.Further, ATX-II elicited potentially arrhythmogenic early afterdepolarizations in myocytes from 0/5 male mice and 3/5 female mice. ConclusionThese data identify variable late I Na as a modulator of gender-dependent arrhythmia susceptibility.
Pulmonary Valve Atresia with Intact Ventricular Septum
Authors: JOHN D. MCARTHUR, SUSIL C. MUNSI, I. P. SUKUMAR, GEORGE CHERIAN
Journal: Circulation (1971)

A case of pulmonary valve atresia with intact ventricular septum' with long survival in the absence of a patent ductus arteriosus, is presented. The patient, alive at 21 years of age, has the anterior descending branch of the left coronary artery originating from the pulmonary artery. Thus, the pulmonary blood supply is obtained from the right coronary artery via intercoronary anastomoses. No similar case has been reported previously.
Abstract LB-206: A novel scaffold that targets the IKK complex
Authors: Vashti C. Bryant, Prakash Radhakrishnan, Michael A. Hollingsworth, Amar Natarajan
Journal: Cancer Research (2011)

Abstract The IκB kinase (IKK) complex is a central component of the NF-κB pathway. The expression of a number of gene products are controlled and regulated by NF-κB. Dysregulation of the NF-κB pathway proteins has been implicated in a number of cancers including pancreatic cancer. A cell-based luciferase reporter assay was used to screen in house chemical libraries and identify NF-κB inhibitors. This led to the identification of quinoxaline urea (QU) analog as a validated hit. We found that QU inhibits the nuclear translocation of p65 in response to TNF-α stimulation. Our studies also indicate that QU inhibits a constitutively active form of the IKK complex. QU induced growth inhibition and apoptosis in a panel of pancreatic cancer cell lines with low-μM potency. NF-κB is an important player in the invasion and metastases of pancreatic cancer. The in vitro migration and matrigel invasion assay results with QU shows that it inhibits the migratory and invasive ability of pancreatic cancer cell lines. QU has comparable activities in all our assays to known NF-κB inhibitors, parthenolide and curcumin, that are in clinical trials for pancreatic cancer therapy. In summary, we present a novel scaffold that targets the constitutively active IKK complex with the potential to be developed as pancreatic cancer therapeutic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-206. doi:10.1158/1538-7445.AM2011-LB-206
Investigating the Role of Natural Selection on Coding Sequence Evolution in Salmonids Through NGS Data Mining
Authors: C. Sauvage, S. Renaut, E. Normandeau, N. Derome, L. Bernatchez
Journal: Molecular Biology and Evolution (2011)

Sequence Evolution in Salmonids Through NGS Data Mining Christopher Sauvage,* Sebastien Renaut, Eric Normandeau, Nicolas Derome, and Louis Bernatchez Departement de Biologie, Institut de Biologie Integrative et des Systemes, Universite Laval, Quebec, Canada Department of Botany, University of British Columbia, Vancouver, British Columbia, Canada *Corresponding author: E-mail: christopher.sauvage.1@ulaval.ca. Associate editor: Douglas Crawford
Standards of Medical Care in Diabetes–2006
Authors: Kingston H. Tseng
Journal: Diabetes Care (2006)

I recently encountered a discrepancy in the American Diabetes Association’s (ADA’s) recommendations regarding conventional versus SI units for HDL cholesterol (1). The article states “raise HDL cholesterol to >40 mg/dl (1.15 mmol/l).” Simple calculation shows that 40 mg/dl = 40 × 0.02586 mmol/l = 1.03 mmol/l, rather than 1.15 mmol/l. The same error is also noted in the 2005 version.

Furthermore, in regard to the ADA’s recommendation to use statin therapy for diabetic patients without overt cardiovascular disease (CVD), the recommendation to treat “regardless of baseline LDL” might have extended beyond the evidence quoted. I …
Challenges to implementing NPfIT: Nothing counts except what is in front of the clinician to use
Authors: Steven Ford
Journal: BMJ (2005)

Junior doctors' shifts and sleep deprivation New on-call rotas do not workEditor-Clearly the editorial by Murray et al on junior doctors' shifts has struck a chord with many, as on-call rotas are something close to many doctors hearts. 1 2 To most it seems the grass is not greener on the other side.Having worked most rotas, be it a traditional one in four, with full weekends, to partial, hybrid, and full shift patterns, I am in a reasonable position to comment on what I think makes a liveable on-call rota.I was under the impression that the European Working Time Directive was set out to improve the health and safety of workers, make working conditions better, but also make life away from work better because doctors would be less tired.The directive scores a "no" against all of these.I find myself more tired at work and at home, less enthusiastic, and less motivated by what is becoming a regular chore.Instead of being on call once a week, I find myself doing an on-call shift two or three times a week (on average), being late home more often than not because fewer juniors are around, and spending less time with my young children.The "old" rota system of a 24 hour oncall, with at least six on a rota, made on-call shifts less frequent, more tolerable, and even enjoyable.It also left plenty of time for training, and so long as there were six or more on rota, it made the annual leave far more flexible and workable.Anaesthetists rarely complained, certainly compared with other specialties' rotas, and everyone knew that however busy, you were always going to go home to a full day off in the morning.Why not listen to those doing the rota, and affected family members, and respect within reason what the workers want to work.
Ten-minute abortions.
Authors: W O Goldthorp
Journal: BMJ (1977)

A service performing very early abortions in a district general hospital uses menstrual aspiration, which enables abortion to be carried out early, easily, safely, and simply. Menstrual aspiration avoids interference with routine gynaecological work and permits an operator to widen his criteria for accepting patients for termination. From September 1975 to April 1977 123 cases were referred and 104 aspirations were performed. Termination of pregnancy failed in only two cases, through inexperience, and infection occurred in only one case. Menstrual aspiration should be performed within 10-18 days of missing a period.
CONSISTENCY OF AGREEMENT BETWEEN INDEPENDENT ASSESSORS OF 3-DIMENSIONAL GLOBAL LONGITUDINAL STRAIN OF RIGHT VENTRICLE USING TRANSTHORACIC ECHOCARDIOGRAPHY IN A POPULATION &gt;50% PULMONARY HYPERTENSION
Authors: Koya Ozawa, Nobusada Funabashi, Tomoko Kamata, Noriyuki Yanagawa, Nobuhiro Tanabe, Koichiro Tatsumi, Fumio Nomura, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2014)
FRIEDRICH'S ATAXIA; ITS RELATION TO THE CONDUCTING PATHS IN THE SPINAL CORD.
Authors: DAVID INGLIS
Journal: JAMA (1891)

At the Congress of American Physicians and Surgeons, Dr. David Inglis, of Detroit, read a paper upon the above subject before the American Neurological Association. He reports in brief, a case of Friedrich's ataxia, in a boy of six years of age, in which the symptoms conformed accurately to Friedrich's own summary of the characters of the disease, viz.: "Impairment in the combination and harmony of movements developing gradually and spreading from the lower to the upper half of the body, and always involving finally the organs of speech; sensibility and the functions of the special senses and of the brain being intact; paralysis of the sphincters and trophic disturbances are absent; less common phenomena are curvature of the spine, sensations of vertigo and nystagmus. From a clinical point of view we must regard the disease as a progressive paralysis of the faculty of combination of movements." A review of
Percentage of glycosylated serum ferritin remains low throughout the course of adult onset Still's disease
Authors: S. Vignes
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To determine the evolution of levels of total serum ferritin and percentage of the glycosylated form in patients with adult onset Still9s disease (AOSD) at the time of diagnosis and during follow up. <h3>METHODS</h3> All patients with AOSD were tested at the time of diagnosis and during follow up. Total serum ferritin levels were analysed by immunoassay, and the percentage of glycosylated ferritin was determined by methods using Sepharose-Con A. <h3>RESULTS</h3> 14 patients (eight women, six men) with AOSD were enrolled. At the time of diagnosis, mean (SD) age was 36 (16) years. Mean initial total serum ferritin was 6350 (1300) μg/l (normal &lt;250 μg/l). The mean initial percentage of glycosylated ferritin was 14.7 (13)% (normal &gt;50%). Mean follow up time was 37 (35) months. At the time of the last examination all patients were in remission except one, who presented a chronic articular form. Total serum ferritin remained high in this single patient and was normal in the 13 others, with a mean of 98 (73) μg/l. In all patients the percentage of glycosylated ferritin remained low, with a mean of 16 (16)%. <h3>CONCLUSION</h3> Total serum ferritin is a marker of the active phase of AOSD. The percentage of glycosylated ferritin is low both in the active phase and in remission. Further studies are needed to confirm these data and to determine their specificity for AOSD before considering any possible use of a low percentage of glycosylated ferritin as a diagnostic tool in suspected AOSD, especially when atypical or previously treated.
Comparison of 131I-MIBG, 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT Scans in a Patient With Extra Adrenal Paraganglioma Associated With SDH-B Gene Mutation
Authors: Rajeev Kasaliwal, Gaurav Malhotra, Anurag Lila, Tushar Bandgar, Nalini S Shah
Journal: Clinical Nuclear Medicine (2015)

Paragangliomas (PGLs) due to succinate dehydrogenase subunit B (SDH-B) mutation can be aggressive. A 40-year-old woman with normetanephrine-secreting, extra-adrenal, abdominal PGL due to SDH-B genetic mutation underwent surgical excision of primary, followed by whole-body I-MIBG scan after 6 months, which showed no abnormality. However, Ga-DOTANOC and F-FDG PET/CT scans showed primary site recurrence, hepatic and skeletal metastasis, with latter scan revealing more lesions. We suggest that F-FDG PET should be done in all patients with PGL due to SDH-B mutations, as it may show additional unsuspected lesions that may be missed by other tracers.
Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL-10-transduced islet-specific Th1 lymphocytes. A gene therapy model for autoimmune diabetes.
Authors: M Moritani, K Yoshimoto, S Ii, M Kondo, H Iwahana, T Yamaoka, T Sano, N Nakano, H Kikutani, M Itakura
Journal: Journal of Clinical Investigation (1996)

Four pancreatic islet-specific CD4+ helper T (Th) 1 (Th1) clones and two Th1 clones transduced with an SRalpha promoter-linked murine IL-10 (mIL-10) cDNA of 2.0-6.0 x 10(6) cells were adoptively transferred to nonobese diabetic (NOD) mice at age 8 d. Cyclophosphamide (CY) was administered at age 37 d (plus CY), and the incidence of diabetes and the histological grade of insulitis were examined at age 47 d. After the adoptive transfer of IL-10-transduced Th1 cells, polymerase chain reaction (PCR) and reverse-transcription (RT)-PCR detected the neo gene and the retrovirus vector-mediated IL-10 mRNA in situ in recipient islets, respectively. RT-PCR detected the decrease of IFN-gamma mRNA relative to IL-10 mRNA in IL-10-transduced Th1 clones in vitro and also in recipient islets. All four wild type Th1 clones plus CY induced the insulitis grade of 2.75 and diabetes in 66% of recipient NOD mice. IL-10-transduced two Th1 clones plus CY induced periinsulitis with the grade of 1.43 and diabetes in 8.0%. The 1:1 mixture of wild type Th1 cells and IL-10-transduced Th1 cells plus CY induced periinsulitis with the grade of 1.85 and diabetes in 20%. The suppression of diabetes through decreasing IFN-gamma mRNA by the tissue-specific delivery of IL-10 to pancreatic islets with IL-10-transduced Th1 cells affords us the starting basis to develop the gene therapy for autoimmune diabetes.
Primary biliary cirrhosis presenting with granulomatous skin lesions.
Authors: D L Jardine, S T Chambers, D J Hart, B A Chapman
Journal: Gut (1994)

A case is described of primary biliary cirrhosis in a 59 year old woman who initially presented with a rash over her lower legs 18 months before diagnosis. Skin biopsy examination showed non-caseating granulomas of the sarcoid type. It is believed that this is the first reported case of primary biliary cirrhosis presenting with a granulomatous rash.
Evaluation of patients with hereditary hemorrhagic telangiectasia with video capsule endoscopy: a single-center prospective study
Authors: S. Chamberlain, J. Patel, J. Carter Balart, J. Gossage Jr, S. Sridhar
Journal: Endoscopy (2007)

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by telangiectasia formation that can lead to small-bowel bleeding. In this study, video capsule endoscopy was used to compare the small-bowel findings observed in patients with HHT with those seen in patients without the condition.We performed capsule endoscopy studies in 93 consecutive patients who were being evaluated for small-bowel bleeding, 38 patients with known or suspected HHT and 55 patients without HHT. Nine patients were excluded because the capsule failed to reach the cecum. The findings in 32 patients with a final diagnosis of HHT and in 48 patients without HHT were recorded and compared.Capsule endoscopy detected telangiectases evenly distributed throughout the small bowel in 26/32 (81%) patients with HHT, compared with 14/48 (29%) in patients without HHT. When active bleeding was observed in patients with HHT (n = 4), the bleeding was within reach of standard small-bowel push enteroscopy in all cases. The presence of five or more gastrointestinal telangiectases by capsule endoscopy had a sensitivity of 75% and a positive predictive value of 86% for diagnosing HHT. Unexpected findings (small-bowel polyps and mass-like lesions) were seen in both groups of patients (6.2% in patients with HHT and 2.1% in patients without HHT).Small-bowel telangiectases were seen in the majority of patients with HHT and were evenly distributed throughout the small bowel. Telangiectases were observed in only a minority of patients who did not have HHT. Actively bleeding small-bowel telangiectases were located in the proximal and mid-small bowel in patients with HHT, all within reach of an enteroscope. We propose a cutoff point of at least five gastrointestinal telangiectases to support a diagnosis of HHT.
Headache doctor found guilty of dishonesty in research misconduct case
Authors: C. Dyer
Journal: BMJ (2015)

<h3>Introduction/Background</h3> Expression of sex hormonal receptors (SHR) had been reported to influence survival outcomes in patients with epithelial ovarian cancer. In present study, we attempted to investigate the association and mechanism between SHR expression and chemosensitivity in epithelial ovarian cancer (EOC). <h3>Methodology</h3> We reviewed 71 patients with EOC who underwent surgery followed by adjuvant chemotherapy and analyzed sex hormone receptors (SHR) immunohistochemical (IHC) expression of tissue samples obtained from these patients. The disease-free survival (DFS), overall survival (OS), and percentage of chemosensitivity were compared between weak and strong SHR IHC expression. The effects of cisplatin administration on cell proliferation in ovarian cancer OC3-VGH cells with different SHR expression were investigated. <h3>Results</h3> Patients with strong androgen (AR) and progesterone receptors (PR) IHC expression had better 5-year DFS, OS, and chemosensitivity. In cell model data, overexpression of AR and PR OC3-VGH cells caused higher sensitivity to cisplatin treatment. OV3-VGH cisplatin resistant clone expressed lower level of AR and PR than wild-type. Overexpression of AR OC3-VGH cells showed higher DNA damage signals after cisplatin treatment. <h3>Conclusion</h3> Our data indicated that strong AR and PR expression were good prognostic factors via the mechanism of better cisplatin sensitivity. Novel therapeutics against AR and PR might be promising for treatment of EOC patients. <h3>Disclosure</h3> Nothing to disclose.
Asymmetry of cellular response as revealed by the skin window technique
Authors: STUART A. GARRIE, PHELPS CRUMP
Journal: British Journal of Dermatology (1973)

Utilizing the skin window technique, symmetry of cellular response was examined by comparing cellular exudates from symmetrical areas of opposite forearms in eleven subjects. Testing the hypothesis that there would be no significant difference between symmetrical sites subjected to the same stimulus at the same time, the percentages of cell types in the cellular exudate were calculated for 126 paired comparisons. A significant difference in the cell types arriving at the skin window sites occurred in seventy‐six out of the 126 paired comparisons (Chi square analysis, P<0.01). This lack of a symmetrical response could be due to an inherent variability of the cellular response or to an inability to manipulate the two sites in exactly the same manner. Although significant differences were found between the above individual matched pairs (Chi square analysis), the ‘t’ test analysis of the pairs grouped by hour revealed no significant difference in mean percentages of cell types between left and right arms at fourteen time intervals. Thus, previous skin window investigations comparing mean percentages of cell types were found to be valid, even though symmetry of cellular response in individual subjects is much less than expected.
Who is at risk of a coronary?
Authors: T Khosla, R G Newcombe, H Campbell
Journal: BMJ (1977)

The Joint Working Party of the Royal College of Physicians and the British Cardiac Society have recently given advice to medical practitioners about preventing coronary heart disease. We have formulated an easy method by which the medical practitioner may apply a rule to identify individuals who are at moderate to high risk of developing the disease. The simple arithmetic requires finding the product of four numbers and can be done with a pocket calculator costing less than pound 10. The four numbers correspond to known values of the four risk variables--age, systolic blood pressure, serum cholesterol levels, and smoking--for a given individual. Tables of relative risk components for men aged 40 to 59 years for coronary heart disease defined by hard criteria (fatal or definite myocardial infarction) have been drawn up. The overall effect of the four risk variables is multiplicative so that some men aged 40 are at far greater risk than some of 55 year olds.
Carrier solutions for low-level intravenous insulin infusion.
Authors: E W Kraegen, L Lazarus, H Meler, L Campbell, Y O Chia
Journal: BMJ (1975)

In the use of low-level intravenous insulin infusion for treating diabetic hyperglycaemia and ketoacidosis adsorption of insulin to containers or plastic infusion apparatus results in significant losses of 60-80% of insulin in dilute physiological saline solution (40 U/l). It is therefore necessary to add protein to the carrier solution to minimize losses and maintain a constant delivery rate. Recovery studies showed that 3.5% w/v polygeline solution (polymer of degraded gelatin) was a suitable medium for this purpose, offering some advantages over human serum albumin. A minimum concentration of 0.5% polygeline was required to ensure adequate delivery of insulin to the patient.
Splenic Infarction Diagnosed Preoperatively by Photoscanning
Authors: Wil B. Nelp
Journal: JAMA (1966)

THE DIAGNOSIS of infarction of the spleen in patients who present with left-upper-quadrant abdominal pain is difficult to prove by the usual diagnostic techniques. Radioisotope photoscanning, after administering isotopes which selectively concentrate in the spleen, is a relatively new and useful diagnostic procedure specifically directed at clarifying splenic disease. The following report of two cases of infarction of the spleen, due to arterial emboli originating from infected vascular prostheses, illustrates the usefulness of photoscanning for the diagnosis of intrasplenic disease. <h3>Techniques of Spleen Scanning</h3> Visualization of the spleen by scanning depends upon attaining a selective concentration of radioactivity in the spleen, which is higher than that in the surrounding tissue. Since the distribution of the isotope within the spleen represents only functioning tissue, areas of destroyed function such as caused by infarction will be delineated as regions without radioactivity. Spleen scanning was originally performed by injecting red blood cells treated
Magnesium, the Mimic/Antagonist of Calcium
Authors: Barton S. Levine, Jack W. Coburn
Journal: New England Journal of Medicine (1984)

Magnesium, the fourth most abundant metal in living organisms, is distributed in three major compartments in the body: 65 per cent in the mineral phase of skeleton, 34 per cent in the intracellular space, and only 1 per cent in the extracellular fluid.1 It is difficult to measure intracellular and bone magnesium, but most data indicate that the bone compartment of magnesium reflects changes in extracellular magnesium, whereas intracellular magnesium remains stable despite wide fluctuations in serum magnesium.Dietary magnesium amounts to approximately 300 to 360 mg (24 to 30 meq) per day in the United States, with principal sources . . .
Quantification of Psychosocial Variables in Intrinsic Asthma Relationship to Physiologic Variability
Authors: Donald L. Dudley, Thomas H. Holmes, Paul P. van Arsdel, jr., Gilberto de Araujo
Journal: Psychotherapy and Psychosomatics (1974)

This was a pilot study of 36 patients with intrinsic asthma which indicates that routine testing of psychosocial assets and life change would be of value in clinical management. Therapeutic attention should be directed to patients with low psychosocial assets and high life change. It is felt that patients in this group should receive additional medical attention and be taught to reduce life change to a level that they can tolerate.