tbuckley/cabot-search huggingface dataset:
Drug points: Bronchospasm associated with cisapride
Authors: P Pillans
Journal: BMJ (1995)

writes: Cisapride seems to facilitate gastrointestinal motility by enhancing the release of acetylcholine from postganglionic nerve endings of the myenteric plexus in the gut.1 The data sheet does not mention the potential to precipitate bronchospasm in patients with asthma. The New Zealand and Australian Adverse Reaction Committees each have a report of bronchospasm, and the Medicines Control Agency, United Kingdom, …
Nodular localized cutaneous amyloidosis: further demonstration of monoclonality of infiltrating plasma cells in four additional Japanese patients
Authors: None Hagari, None Mihara, None Konohana, None Ueki, None Yamamoto, None Koizumi
Journal: British Journal of Dermatology (1998)

Nodular localized cutaneous amyloidosis (NLCA) is a disorder characterized by deposition of amyloid derived from immunoglobulin light chains. We used semi-nested polymerase chain reaction (PCR) to analyse archival paraffin-embedded sections from a previous patient and from four additional, previously reported patients with NLCA to determine whether involvement of monoclonal plasma cells is a universal feature of this condition. The semi-nested PCR analysis revealed one or two amplified bands, around 100-120 bp, for all five cases of NLCA, although the yields varied from case to case. These results suggest that clonal expansion of plasma cells in NLCA may occur locally.
Comparative Safety of Vascular Closure Devices and Manual Closure Among Patients Having Percutaneous Coronary Intervention
Authors: Hitinder S. Gurm, Carrie Hosman, David Share, Mauro Moscucci, Ben B. Hansen
Journal: Annals of Internal Medicine (2013)

Background: The role of vascular closure devices (VCDs) in patients having percutaneous coronary intervention (PCI) is controversial, and recommendations for use vary. Objective: To examine the use of and outcomes associated with VCDs in real-world practice. Design: Observational cohort study. Setting: 32 hospitals in Michigan that participate in a large multicenter quality improvement collaborative. Patients: Consecutive patients having emergent and nonemergent PCI from 2007 to 2009. Measurements: Vascular complications and the need for transfusion. Results: Of the 85 048 PCIs performed during the study that met the inclusion criteria, 28 528 (37%) procedures used VCDs. In propensity score–matched analysis, VCDs were associated with reductions in vascular complications (odds ratio [OR], 0.78 [95% CI, 0.67 to 0.90]; P = 0.001) and postprocedure transfusions (OR, 0.85 [CI, 0.74 to 0.96]; P = 0.011). These findings were consistent across many prespecified subgroups except for patients with a body mass index (BMI) less than 25 kg/m2 and those treated with platelet glycoprotein (GP) IIb/IIIa inhibitors, in whom the benefit of VCDs over manual closure was attenuated. When the specific subtypes of vascular complications were evaluated, VCDs were associated with fewer hematomas (OR, 0.69 [CI, 0.58 to 0.83]; P < 0.001) or pseudoaneurysms (OR, 0.54 [CI, 0.38 to 0.76]; P < 0.001) but an increase in the odds of retroperitoneal bleeding (OR, 1.57 [CI, 1.12 to 2.20]; P = 0.009). Limitation: Unmeasured confounding cannot be excluded despite the study having measured and balanced many confounders. Conclusion: Vascular closure devices were associated with a significant reduction in vascular complications and need for transfusion in this large cohort of patients having transfemoral PCI. This benefit was lost in patients receiving GP IIb/IIIa inhibitors and those with normal or lean BMI and was counterbalanced by a small increase in the more serious risk for retroperitoneal bleeding. Primary Funding Source: Blue Cross Blue Shield of Michigan and the National Science Foundation.
Polyclonal hematopoiesis with variable telomere shortening in human long-term allogeneic marrow graft recipients
Authors: George Mathioudakis, Rainer Storb, Peter A. McSweeney, Beverly Torok-Storb, Peter M. Lansdorp, Tim H. Brümmendorf, M. John Gass, Eileen M. Bryant, Jan Storek, Mary E. D. Flowers, Ted Gooley, Richard A. Nash
Journal: Blood (2000)
Abstract 16820: CaMKIIδc Transgenic Mice Develop Spontaneous Ventricular Arrhythmias Which Can Be Suppressed by Inhibition of Late Na+ Current
Authors: Maria Arolfo, Liguo Chi, Aliya Zeng, Nesrine El-Bizri, Joan Brown, Sridharan Rajamani, Luiz Belardinelli, Arvinder Dhalla
Journal: Circulation (2014)

Introduction: It has been shown that activated CaMKII can phosphorylate cardiac Na+ channels that leads to an enhanced late Na current (INaL). We hypothesized that enhanced INaL plays an important role in arrhythmogenesis linked to increased CaMKII activity. To test this hypothesis we determined the effect of a selective INaL inhibitor GS-967 on spontaneously occurring ventricular arrhythmias in mice overexpressing CaMKIIδc (TG). Methods: TG (n=6) and wild type (WT, n=3) mice at age 8 week (wk) were instrumented with telemetry transmitters to record ECG. ECG were recorded continuously starting 1 wk post- surgery (age 9 wk) until age 19 wk. Incidence and burden of arrhythmias were evaluated at ages 9, 11, 13, 15, 17 and 19 wks using DSI ECG Pro software. At age 17 wk, when arrhythmia burden was relatively stable, mice were treated with a single dose of GS-967 (1 mg/kg, i.p.) or vehicle. After 4 days of washout, the treatment was repeated in a cross-over manner. Arrhythmia burden was quantified over a duration of 15-hours post-treatment. Using patch clamp technique, INaL was measured in ventricular myocytes isolated from both TG and WT mice at 17 wk age. Results: Incidence and burden of spontaneous ventricular arrhythmias increased progressively with age in TG mice. Between age 9 and 11 wks, 50% of TG mice had an arrhythmia burden ≥ 5 minutes/24 hours. The incidence increased to 83% at wk 13, 15, 17 and to 100% at 19 wks and the burden increased to 71 ± 35 min/24 hr at 17 wk. A single dose of GS-967 significantly decreased arrhythmia burden from 42.5 ± 9.6 min (treated with vehicle) to 9.4 ± 4.3 min (p&lt;0.05) during a 15-hr period. No arrhythmias were observed in WT mice during the course of the study. INaL was enhanced by more than 2-fold in myocytes isolated from TG mice compared to WT (0.2±0.03 vs. 0.08±0.02 pA/pF, n=16 each, p&lt;0.05). GS-967 caused a concentration-dependent reduction of INaL (50.5±3.4% at 0.3 μM, n=7; and 91±5.2% at 1 μM, n=4). Conclusions: This is the first report to show a reduction of spontaneously occurring ventricular arrhythmias by inhibition of INaL indicating a key role for INaL in CaMKII associated arrhythmogenesis.
ACUTE TOXIC NECROSIS OF THE LIVER FOLLOWING THE USE OF SULFANILAMIDE
Authors: HOLLIS K. RUSSELL, M.D.
Journal: Annals of Internal Medicine (1940)

ExcerptThis case is being reported because of the rarity of such severe liver damage following the use of this drug and to emphasize the importance of close observation of every patient receiving sulfanilamide or closely allied drugs.CASE REPORTThe patient was a white man, 46 years of age. The family and personal past history were without record of value. During the summer of 1938 he had complained of increasing nervousness and the presence of a small lump in the midline of the neck. He consulted his doctor who noted that his pulse varied between 87 and 105. The cardiac...
Analysis of the clinical feature of 383 patients with lung cancer
Authors: Yanbin Zhou, Yinhuan Li, Wanling Huang, Xingdong Cai, Qingli Zeng, Lixia Huang
Journal: European Respiratory Journal (2011)

Objective: To investigate the clinical feature of lung cancer.

Methods: We retrospectively analyzed the clinical data of inpatients diagnosed with primary bronchogenic carcinoma who registered in our hospital between 2007 and 2008.

Results: The age of onset of lung cancer was 59 years old. 50.1% of the patients had a history of smoking, 93.8% of whom were males. Coughing, expectoration, emaciation, hemoptysis, chest pain, dyspnea and pyrexia were the most common symptoms. The levels of NSE and CYFRA21-1 in males were higher than those in females, and the levels of serum CYFRA21-1 in senile were higher than those in non-senile. The levels of serum NSE and CYFRA21-1 in smokers were higher than those in non-smokers, while they were higher in patients with central type lung cancer than those in patients with peripheral type lung cancer. The levels of serum NSE in small cell lung cancer patients were higher than those in non-small cell lung cancer patients. The levels of CEA in patients with adenocarcinoma were higher than those in patients with squamous cell carcinoma, while the levels of serum CYFRA21-1 were higher in the latter. The more advanced the disease was, the higher the levels of serum CEA, NSE and CYFRA21-1 were. Carcinoma was most commonly seen in the upper lobes of both sides of the lungs. 68.6% of lung cancer belonged to peripheral type. Adenocarcinoma and squamous cell carcinoma were the most common pathological type. 66.0% of lung cancer patients were in advanced stage when diagnosed, and 55.2% had metastasis to mediastinal lymph nodes. Bones were the most common sites of metastasis.

Conclusions: The combined detection of serum CEA, NSE and CYFRA21-1 could do some help to identify of lung cancer.
Abstract 15998: Rho Kinase Inhibition Prevents the Pressor and Sympatho-Excitatory Effects of Central Angiotensin-II Infusion in Conscious Rabbits
Authors: Peter R Pellegrino, Alicia M Schiller, Karla K Haack, Irving H Zucker
Journal: Circulation (2014)

Introduction:  Elevated sympathetic tone and activation of the renin-angiotensin system are pathophysiologic hallmarks of diseases like chronic heart failure, hypertension, chronic kidney disease, and obstructive sleep apnea, all of which have compelling burdens and therapeutic needs. The RhoA/Rho kinase pathway is an important mediator of the effects of Angiotensin-II (AngII) in the periphery, but the functional role of this pathway in the brain in AngII-induced sympatho-excitation is not well-characterized.   Hypothesis:  We hypothesized that central inhibition of the RhoA/Rho kinase pathway prevents AngII-mediated autonomic dysfunction in rabbits.   Methods:  Each rabbit received all four of the following intracerebroventricular infusion treatments for two weeks in random order: AngII, the Rho kinase inhibitor Fasudil (Fas), AngII and Fas, and vehicle infusion via osmotic minipump. After two weeks, the treatment was washed out with vehicle infusion for 7-14 days. Baseline recordings of mean arterial pressure (MAP) and heart rate (HR) were acquired throughout treatment. After ten days of infusion, cardiac sympathetic tone and sympathetic vasomotor tone were assessed by the change in HR after metoprolol and change in MAP after hexamethonium, respectively.   Results:  AngII treatment resulted in a pressor effect that was blocked with Fas co-infusion (A). Both cardiac sympathetic tone (B) and sympathetic vasomotor tone (C) were increased with AngII infusion; this sympatho-excitation was abrogated by co-infusion of Fas. Each of these measures showed a significant interaction between AngII and Fas, indicating that the pressor and sympatho-excitatory responses of central AngII are mediated by the RhoA/Rho kinase pathway.   Conclusions:  These data indicate that inhibition of the Rho kinase pathway centrally could act as a therapeutic brake on the positive feedback between central renin-angiotensin system activation and sympathetic outflow in many diseases.
Abstract P1-16-07: Translating the concept of intrinsic subtypes into an oncoplastic cohort of more than 1000 patients-predictors of recurrence and survival
Authors: Mahdi Rezai, Stephanie Kellersmann, Sarah Knispel, Rainer Kimmig, Peter Kern
Journal: Cancer Research (2015)

Abstract Introduction: The concept of breast cancer experienced a paradigm shift by Sørlie T. et al. with intrinsic subtypes as prognostic classification of breast cancer [1]. We validated this concept in a large cohort study of oncoplastic surgery. Patients and methods: We analysed 1035 patients with oncoplastic surgery (2004-2009) and survival parameters related to histopathological approximated intrinsic subtypes. Data were retrieved from customized questionnaires and patients charts. Survival data were determined from cancer registries. Results: A total of 944 patients with primary unilateral breast cancer, median age 58 years, were eligible for analysis. At a median follow-up of 5.3 years, LRR was 4.1%, with 5-year-OS of 94.5% and DFS of 90.9%. Stage distribution was as follows: T1a 3%, T1b 12 %, T1c 44,2 % and T2 was 22,1%. 70,4 % of patients were nodal-negative and nodal involvement was predominantly low. Intrinsic subtypes, not T-size, nodal-status, resection margin width nor histopathology, governed the prognosis of this cohort. Triple-negative and Her2 non luminal breast cancer had the highest recurrence and the lowest survival rates compared to Luminal A: Recurrence TNBC 11,3 %, Her2pos non luminal 9,3 %, Luminal A 2,5 %; Overall survival: TNBC 91,3 %, Her2 non luminal 93,7 %; Luminal A: 96,3 %. Our data confirmed the intrinsic subtype concept on a large basis in oncoplastic surgery. (1) Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001; 98: 10869–10874. Citation Format: Mahdi Rezai, Stephanie Kellersmann, Sarah Knispel, Rainer Kimmig, Peter Kern. Translating the concept of intrinsic subtypes into an oncoplastic cohort of more than 1000 patients-predictors of recurrence and survival [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-16-07.
“Oxygen Effect” and Tumor Size as Related to Response of C3H/Ba Adenocarcinoma to Local X Irradiation
Authors: H. Suit, L. Schlachter, J.R. Andrews
Journal: JNCI Journal of the National Cancer Institute (1960)

The C3H/Ba mammary adenocarcinoma transplanted into the thigh muscle of the C3H/He mouse, the inbred strain of mice in which the tumor originated, was studied by irradiation in vivo with an opposed pair of 250 kv. X-ray beams. Tumors 7 to 10 mm. in diameter were lethally damaged by 5500 r in greater numbers than tumors 10 to 15 mm. in diameter. When the treatment was given while the animals breathed 100 percent O2 under 2 atmospheres of pressure instead of air at 1 atmosphere of pressure, results with the small (7–10 mm.) tumors indicated that the increased oxygen tension slightly enhanced the “cure rate”; tumors 10 to 15 mm. in diameter did not show a greater “cure rate” if the therapy were given under increased oxygen tension. The data show that there is a rapid and progressive anemia (decrease in hematocrit) with growth of the tumor.
Abstract 13184: An Elevated Level of N-terminal Pro-brain Natriuretic Peptide is Associated With the Development of Good Collateral Circulation in Patients Undergoing Primary Percutanous Coronary Intervention After St Segment Elevation Myocardial Infarction?
Authors: Jang Hoon Lee, Jae Hee Kim, Se Yong Jang, Sun Hee Park, Myung Hwan Bae, Dong Heon Yang, Hun Sik Park, Yongkeun Cho, Shung Chull Chae
Journal: Circulation (2014)

Background:  Although N-terminal pro-brain natriuretic peptide (NT-proBNP) is released by ventricular myocardium as a result of increased myocardial wall stress, NT-proBNP was recently demonstrated to be a potential stimulator of angiogenesis and arteriogenesis. However, little is known about the correlation between NT-proBNP level and collateral formation in patients undergoing primary percutaneous coronary intervention (PCI) after ST segment elevation myocardial infarction (MI).   Methods:  Between November 2005 and November 2011, 857 eligible patients were analyzed in this study. Serum NT-proBNP levels were measured at the time of admission. Collateral circulation (CC) was graded according to Rentrop’s classification. Grade 0 and 1 are regarded as poor, and grade 2 and 3 are regarded as good CC.   Results:  Overall, 429 (50.1%) had angiographic evidence of CC including 265 (30.9%) with grade 1 and 164 (19.1%) with grade 2/3. The patients with good CC had a more typical chest pain, preinfarction angina, previous coronary heart disease (CHD), non-left anterior descending artery (LAD)-related MI, multivessel disease, pre-TIMI flow grade 0/1, and longer symptom-to-door (STD) time. Log-transformed NT-proBNP level was positively correlated with Rentrop collateral score (r=0.148, p   Conclusions:  An elevated level of serum NT-proBNP is independently associated with collateral development in patients undergoing primary PCI.
Doctors should identify and treat problem drinkers
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

Everyone admitted to hospital should be screened for alcohol misuse in order to stem the rise in deaths and diseases related to excessive drinking, suggests a report from the Royal College of Physicians.

As much as 12% of the money spent on NHS hospitals is estimated to go towards treating alcohol induced diseases and problems. But although the conditions are treated, the problem that caused them in the first place—alcohol misuse—is ignored, said the authors of the report.

If the …
The Rheumatoid Arthritis Risk Gene <i>LBH</i> Regulates Growth in Fibroblast‐like Synoviocytes
Authors: Anna‐Karin H. Ekwall, John W. Whitaker, Deepa Hammaker, William D. Bugbee, Wei Wang, Gary S. Firestein
Journal: Arthritis & Rheumatology (2015)

Fibroblast-like synoviocytes (FLS) are key players in the synovial pathology of rheumatoid arthritis (RA). Currently, there is no treatment that specifically targets these aggressive cells. By combining 3 different "omics" data sets, i.e., 1) risk genes in RA, 2) differentially expressed genes, and 3) differential DNA methylation in RA versus osteoarthritis (OA) FLS, we identified LBH (limb bud and heart development) as a candidate gene in RA. The present study was undertaken to define the role of this gene in FLS. Synovial tissue specimens from RA and OA patients were collected at the time of joint replacement surgery. LBH expression was silenced using small interfering RNA or overexpressed using an LBH expression vector in primary FLS. Gene expression profiles were determined by microarray and assessed using Ingenuity Pathway Analysis. Effects of modified LBH expression were investigated in functional assays. LBH was expressed in the synovial lining layer in patients with RA. Transforming growth factor β1 significantly increased LBH expression in primary FLS, and platelet-derived growth factor BB decreased it. Pathway analysis of the transcriptome of LBH-deficient FLS compared to control FLS identified "cellular growth and proliferation" as the most significantly enriched pathway. In growth assays, LBH deficiency increased FLS proliferation. Conversely, LBH overexpression significantly inhibited cell growth. Cell cycle analysis demonstrated a marked increase in cells entering the cell cycle in LBH-deficient FLS compared to controls. LBH did not alter apoptosis. LBH is a candidate gene for synovial pathology in RA. It is regulated by growth factors and modulates cell growth in primary FLS. Our data suggest a novel mechanism for synovial intimal hyperplasia and joint damage in RA.
Running behind a tourist: leisure-related skin cancer prophylaxis
Authors: S. Tan, C. Sinclair, P. Foley
Journal: British Journal of Dermatology (2012)

The most important risk factor in the development of skin cancer is exposure to ultraviolet (UV) radiation. Cumulative lifetime UV radiation exposure has been shown to be most important in the pathogenesis of squamous cell carcinoma, whereas intermittent high-dose UV radiation exposure in childhood and adolescence may be more important in the aetiology of basal cell carcinoma and cutaneous malignant melanoma. Using established methodology and best available estimates on UV-related mortality and morbidity, it has been estimated that annually around 1·5 million disability-adjusted life years are lost through excessive exposure to UV radiation. Skin cancer is a significant health problem and its burden is such that it causes the health system more to treat than any other forms of cancer. Prevention is the key action in managing skin cancer at a population level. Investment in prevention programmes such as SunSmart encourages protective behaviours that will reduce the human and financial costs of skin cancer.
Lesson of the Week: Hypopharyngeal tumours may be missed on flexible oesophagogastroscopy
Authors: J E Fenton, S Hone, P Gormley, T P O'Dwyer, D P McShane, C I Timon
Journal: BMJ (1995)

Patients with dysphagia may be referred by their general practitioners to either the otoloaryngology or the gastroenterology service, so both specialties should complement each other in the diagnosis and management of this symptom. One cause of dysphagia requiring exclusion is hypopharyngeal carcinoma. Tumours of the hypopharynx and the cervical oesophagus comparise 10% of malignancies affecting the upper part of the gastrointestinal tract from the hypopharynx to the gastric cardia.1 The pyriform fossa and posterior pharyngeal wall are affected in about 60% of these cases.2 These tumours are usually late in presenting because the hypopharynx is a wide and expansile part of the digestive tract and symptoms are moderate until the malignancy is well advanced. The overall survival rate is disappointing (25-30% at five years2), but earlier diagnosis may improve this.

Bingham et al reported a study of 10 cases of pharyngeal and hypopharyngeal causes of dysphagia that were missed or inadequately assessed on fibreoptic oesophagogastroscopy.3 Flexible endoscopy after a barium swallow examination is the routine protocol for the investigation of dysphagia. This is sufficient for the diagnosis …
Different Ways to Describe the Benefits of Risk-Reducing Treatments
Authors: Peder A. Halvorsen, Randi Selmer, Ivar Sønbø Kristiansen
Journal: Annals of Internal Medicine (2007)

Patients respond differently when given equivalent but different descriptions of the outcomes of a treatment. Halvorsen and colleagues randomly assigned 1754 healthy people to receive 1 of 3 survey...