tbuckley/cabot-search huggingface dataset:
PTH-188 Small Bowel Diaphragm Disease: Diagnosis with Capsule Endoscopy and Treatment with Budesonide
Authors: R Pandey, M Khan, N Van Someren, K Besherdas
Journal: Gut (2013)

<h3>Introduction</h3> Diaphragm disease is characterised by strictures that mainly occur in the small intestine, resulting from the use of non-steroidal anti-inflammatory drugs. It may present with vague gastrointestinal symptoms or as a surgical emergency requiring laparotomy. Most cases are diagnosed retrospectively at laparotomy. Laparoscopy and various radiological imaging modalities are often inconclusive. Capsule endoscopy effectively diagnoses diaphragm disease pre-operatively. Following withdrawal of the offending NSAID, surgical resection, strictureplasty and double balloon enteroscopy have all been used as potential treatments. Specific drug treatment of small bowel diaphragm disease has not been described. We present a case series of three patients who were diagnosed with Diaphragm disease at capsule endoscopy and responded to Budesonide therapy. <h3>Methods</h3> Case notes of three patients with a confirmed diagnosis of Diaphragm Disease were analysed, with respect to presenting symptoms, duration of symptoms, investigations, treatment and follow-up. <h3>Results</h3> Three female patients between the ages of 56 and 72 presented with gastrointestinal symptoms, including abdominal pain, nausea, vomiting, bloating and loose stool. Symptoms were present from a range of two months to four years before their presentation to secondary care. All patients had a history of regular NSAID use and were investigated with gastroscopy, colonoscopy and CT abdomen, all of which were normal. Small bowel MRI was also normal in two patients (Fig.1). Capsule endoscopy in all patients demonstrated characteristic features of diaphragm disease (Fig.2). All patients received a tapering dose of Budesonide, starting at a dose of 9mg. A symptomatic response was observed in all patients. One patient has now been started on Azathioprine to maintain long term remission. Two remain on reducing doses of steroid with a significant improvement in symptoms. <h3>Conclusion</h3> Diaphragm disease is an under recognised clinical entity that can present in a variety of ways. It can be difficult to diagnose with routine endoscopy or conventional radiology. Capsule endoscopy appears to be the most sensitive test. Clinicians should have a high index of suspicion for this condition, particularly in the context of NSAID use and chronic gastrointestinal symptoms. Budesonide appears to be an effective therapy for Diaphragm Disease, and it seems likely that long-term therapy with azathioprine can maintain remission. However this is an observational study with a small number of patients. Further research is required to validate this as successful, viable, evidence based treatment option. <h3>Disclosure of Interest</h3> None Declared.
Debating the definition of airflow obstruction: time to move on?
Authors: M. R. Miller, O. F. Pedersen, R. Pellegrino, V. Brusasco
Journal: European Respiratory Journal (2009)

The clinical practice of medicine involves accurate history taking and appropriate clinical examination, followed by the formulation of possible diagnoses to account for the patient's condition. This usually leads to investigations being undertaken to confirm or refute the possible diagnoses. These investigations may be of a visual nature, such as imaging (radiology, magnetic resonance imaging or ultrasound) or endoscopy, or may be the measurement of physiological indices, such as blood pressure, height, weight, lung function or measurements from blood tests. For most measurements, clinicians are used to the concept of accepted normal ranges, which may be different for males and females. These ranges may be quite distinct and relatively invariable. For other measurements the situation is less clear, e.g. blood pressure, for which the acceptable ranges may be defined by their relationship to survival and risk of adverse outcome 1.

In lung function tests, the normal ranges have usually been obtained from healthy nonsmoking subjects and are dependent on a number of other aspects related to the individual subject in question, namely their age, sex, height and ethnic background 2. This complicates the way in which a clinician can quickly interpret whether a subject's result is abnormal. The American Thoracic Society/European Respiratory Society task force on the standardisation of lung function testing has recommended that a given test is said to be abnormal when the measured value is below the lower limit of normality (LLN), defined as 1.645 standard deviations below predicted 3. However, an alternative way to define a lower limit for deciding on the presence of airflow obstruction for chronic obstructive pulmonary disease (COPD), based on the ratio of forced expiratory volume in 1 s (FEV1) to forced …
Fibrin Foam as a Hemostatic Agent in Suprapubic Prostatectomy
Authors: William C. Quinby, Ernest K. Landsteiner
Journal: New England Journal of Medicine (1945)

OF THE many problems presented by the operation of prostatectomy none are of more importance than that of the adequate control of bleeding from the prostatic cavity after the gland has been enucleated. Whether the prostate is approached through the urethra, by way of the perineum or by the suprapubic route, this problem remains of equal importance and difficulty. The literature of prostatic surgery abounds with many methods and devices for hemostasis that need no elaboration. In general at the present such devices consist of one sort or another of catheters and elastic dilatable bags, which after distention with fluid . . .
Low Risk-Factor Profile and Long-term Cardiovascular and Noncardiovascular Mortality and Life Expectancy
Authors: Jeremiah Stamler, Rose Stamler, James D. Neaton, Deborah Wentworth, Martha L. Daviglus, Dan Garside, Alan R. Dyer, Kiang Liu, Philip Greenland
Journal: JAMA (1999)

ContextThree major coronary risk factors—serum cholesterol level, blood pressure, and smoking—increase incidence of coronary heart disease (CHD) and related end points. In previous investigations, risks for low-risk reference groups were estimated statistically because samples contained too few such people to measure risk.ObjectiveTo measure long-term mortality rates for individuals with favorable levels for all 3 major risk factors, compared with others.DesignTwo prospective studies, involving 5 cohorts based on age and sex, that enrolled persons with a range of risk factors. Low risk was defined as serum cholesterol level less than 5.17 mmol/L (&lt;200 mg/dL), blood pressure less than or equal to120/80 mm Hg, and no current cigarette smoking. All persons with a history of diabetes, myocardial infarction (MI), or, in 3 of 5 cohorts, electrocardiogram (ECG) abnormalities, were excluded.Setting and ParticipantsIn 18 US cities, a total of 72,144 men aged 35 through 39 years and 270,671 men aged 40 through 57 years screened (1973-1975) for the Multiple Risk Factor Intervention Trial (MRFIT); in Chicago, a total of 10,025 men aged 18 through 39 years, 7490 men aged 40 through 59 years, and 6229 women aged 40 through 59 years screened (1967-1973) for the Chicago Heart Association Detection Project in Industry (CHA) (N = 366,559).Main Outcome MeasuresCause-specific mortality during 16 (MRFIT) and 22 (CHA) years, relative risks (RRs) of death, and estimated greater life expectancy, comparing low-risk subcohorts vs others by age strata.ResultsLow-risk persons comprised only 4.8% to 9.9% of the cohorts. All 5 low-risk groups experienced significantly and markedly lower CHD and cardiovascular disease death rates than those who had elevated cholesterol level, or blood pressure, or smoked. For example, age-adjusted RRs of CHD mortality ranged from 0.08 for CHA men aged 18 to 39 years to 0.23 for CHA men aged 40 through 59 years. The age-adjusted relative risks (RRs) for all cardiovascular disease mortality ranged from 0.15 for MRFIT men aged 35 through 39 years to 0.28 for CHA men aged 40 through 59 years. The age-adjusted RR for all-cause mortality rate ranged from 0.42 for CHA men aged 40 through 59 years to 0.60 for CHA women aged 40 through 59 years. Estimated greater life expectancy for low-risk groups ranged from 5.8 years for CHA women aged 40 through 59 years to 9.5 years for CHA men aged 18 through 39 years.ConclusionsBased on these very large cohort studies, for individuals with favorable levels of cholesterol and blood pressure who do not smoke and do not have diabetes, MI, or ECG abnormalities, long-term mortality is much lower and longevity is much greater. A substantial increase in the proportion of the population at lifetime low risk could contribute decisively to ending the CHD epidemic.
Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses in <i>BRCA</i> Carrier Ovarian Cancer Correlating With Platinum-Free Interval
Authors: Peter C. Fong, Timothy A. Yap, David S. Boss, Craig P. Carden, Marja Mergui-Roelvink, Charlie Gourley, Jacques De Greve, Jan Lubinski, Susan Shanley, Christina Messiou, Roger A'Hern, Andrew Tutt, Alan Ashworth, John Stone, James Carmichael, Jan H.M. Schellens, Johann S. de Bono, Stan B. Kaye
Journal: Journal of Clinical Oncology (2010)

Purpose Selective tumor cell cytotoxicity can be achieved through a synthetic lethal strategy using poly(ADP)-ribose polymerase (PARP) inhibitor therapy in BRCA1/2 mutation carriers in whom tumor cells have defective homologous recombination (HR) DNA repair. Platinum-based chemotherapy responses correlate with HR DNA repair capacity. Olaparib is a potent, oral PARP inhibitor that is well tolerated, with antitumor activity in BRCA1/2 mutation carriers. Patients and Methods Patients with BRCA1/2-mutated ovarian cancer were treated with olaparib within a dose-escalation and single-stage expansion of a phase I trial. Antitumor activity was subsequently correlated with platinum sensitivity. Results Fifty patients were treated: 48 had germline BRCA1/2 mutations; one had a BRCA2 germline sequence change of unknown significance, and another had a strong family history of BRCA1/2-associated cancers who declined mutation testing. Of the 50 patients, 13 had platinum-sensitive disease, 24 had platinum-resistant disease, and 13 had platinum-refractory disease (according to platinum-free interval). Twenty (40%; 95% CI, 26% to 55%) achieved Response Evaluation Criteria in Solid Tumors (RECIST) complete or partial responses and/or tumor marker (CA125) responses, and three (6.0%) maintained RECIST disease stabilization for more than 4 months, giving an overall clinical benefit rate of 46% (95% CI, 32% to 61%). Median response duration was 28 weeks. There was a significant association between the clinical benefit rate and platinum-free interval across the platinum-sensitive, resistant, and refractory subgroups (69%, 45%, and 23%, respectively). Post hoc analyses indicated associations between platinum sensitivity and extent of olaparib response (radiologic change, P = .001; CA125 change, P = .002). Conclusion Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity.
ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling
Authors: Jane T. Seto, Kate G.R. Quinlan, Monkol Lek, Xi Fiona Zheng, Fleur Garton, Daniel G. MacArthur, Marshall W. Hogarth, Peter J. Houweling, Paul Gregorevic, Nigel Turner, Gregory J. Cooney, Nan Yang, Kathryn N. North
Journal: Journal of Clinical Investigation (2013)

α-Actinin-3 deficiency occurs in approximately 16% of the global population due to homozygosity for a common nonsense polymorphism in the ACTN3 gene. Loss of α-actinin-3 is associated with reduced power and enhanced endurance capacity in elite athletes and nonathletes due to "slowing" of the metabolic and physiological properties of fast fibers. Here, we have shown that α-actinin-3 deficiency results in increased calcineurin activity in mouse and human skeletal muscle and enhanced adaptive response to endurance training. α-Actinin-2, which is differentially expressed in α-actinin-3-deficient muscle, has higher binding affinity for calsarcin-2, a key inhibitor of calcineurin activation. We have further demonstrated that α-actinin-2 competes with calcineurin for binding to calsarcin-2, resulting in enhanced calcineurin signaling and reprogramming of the metabolic phenotype of fast muscle fibers. Our data provide a mechanistic explanation for the effects of the ACTN3 genotype on skeletal muscle performance in elite athletes and on adaptation to changing physical demands in the general population. In addition, we have demonstrated that the sarcomeric α-actinins play a role in the regulation of calcineurin signaling.
Carminomycin I Is an Apoptosis Inducer That Targets the Golgi Complex in Clear Cell Renal Carcinoma Cells
Authors: Girma M. Woldemichael, Thomas J. Turbyville, W. Marston Linehan, James B. McMahon
Journal: Cancer Research (2011)

Clear cell renal cell carcinoma (CCRCC) evolves due to mutations in the Von Hippel-Lindau (VHL) tumor suppressor gene. Although the loss of VHL enables survival and proliferation of CCRCC cells, it is also expected to introduce vulnerabilities that may be exploited for therapeutics discovery. To this end, we developed a high-throughput screen to identify small molecules derived from plants, microorganisms, and marine organisms to which CCRCC cells are sensitive. Screening over 8,000 compounds using this approach, we report here the identification of the microbially derived compound carminomycin I (CA) as an effective inhibitor of VHL-defective (VHL(-/-)) CCRCC cell proliferation. CA also induced apoptosis in CCRCC cells by a mechanism independent of p53 or hypoxia-inducible factor 2. We found that P-glycoprotein (P-gp) sequestered CA within the Golgi complex. Interestingly, Golgi sequestration was critical for the antiproliferative effects of CA and P-gp inhibitors abrogated this activity. Furthermore, CA induced cleavage of the Golgi protein p115 and the translocation of its C-terminal fragment to the nucleus. Finally, examination of the activity of the VHL-interacting Golgi protein, endoplasmic reticulum-Golgi intermediate compartment, ERGIC-53 showed that VHL could mediate protection from CA in CCRCC cells. Our natural product-based screening approach has revealed the P-gp-mediated localization of anticancer compounds within the Golgi in CCRCC cells as a potential strategy of targeting VHL-deficient CCRCC cells.
Gladys Elsa McArthur Strang (Mrs Scarlett)
Authors: Fiona Kingston
Journal: BMJ (2006)

Former consultant psychiatrist High Croft Hospital, Birmingham (b 1913; q St Andrews 1937; MRCPsych), died from metastatic renal carcinoma on 18 January 2006.    ![][1] 

Gladys went to St Andrews …

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Primary care: an investment opportunity you can't refuse?
Authors: Des Spence
Journal: BMJ (2011)

Proposed new legislation and a political climate sensitive to the private sector offer a rare investment opportunity in the NHS.

Currently, primary care is dominated by small partnerships. And, like pharmacy and veterinary medicine, the workforce is increasingly salaried and often working part time. Management decisions are now concentrated in a dwindling number of partners, many of whom are close to retirement. Medical practices cannot be acquired in the traditional sense because there is no sale of “goodwill.” However, there is an opportunity to start combining these partnerships …
Human Disease Transferred to Mice: Myasthenia Gravis
Authors: David M. Dawson
Journal: New England Journal of Medicine (1977)

The current issue of the Journal describes an important step of a new line of investigation into myasthenia gravis. Two crucial observations preceded this study.1 , 2 Patrick and Lindstrom found, by chance, that injection of purified acetylcholine receptor to induce an antibody caused experimental myasthenia in rabbits.3 Secondly, Fambrough, Drachman and Satyamurti4 used an autoradiographic technic to show that human myasthenic muscle-biopsy samples contained only 30 per cent of the expected amount of neuromuscular acetylcholine receptor. Since then these basic observations have been extended. Antibodies, which have been found in nearly all patients with myasthenia, cross-react with receptor protein of diverse . . .
TCT-736 Impact Of Pulmonary Hypertension Etiology According To Invasive Hemodynamic Definitions On Clinical Outcomes In Patients With Severe Symptomatic Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation
Authors: Crochan J. O'Sullivan, Osman Ceylan, Ernest Spitzer, Peter Wenaweser, Stefan Stortecky, Thomas Zanchin, Thomas Pilgrim, Ahmed Khattab, Bernhard Meier, Stephan Windecker, Lutz Buellesfeld
Journal: Journal of the American College of Cardiology (2014)
Rhinovirus Infections in an Industrial Population
Authors: Jack M. Gwaltney, J. Owen Hendley, Gilbert Simon, William S. Jordan
Journal: New England Journal of Medicine (1966)

RHINOVIRUSES have been associated with 10 to 30 per cent of acute upper respiratory illnesses in several groups of adults.1 2 3 4 5 6 In March, 1963, a study was undertaken to define the etiology and epidemiology of acute respiratory disease in a population of working adults, and the role of a number of viruses was studied initially. Coincident with the beginning of the investigation, improvements in technology occurred that facilitated the isolation of rhinoviruses and shifted emphasis to these agents. During the first three years of the study, the period considered in this report, approximately a quarter of the acute respiratory illnesses were . . .
Motor function of gastric antrum and pylorus for evacuation of low and high viscosity meals in dogs.
Authors: J Prove, H J Ehrlein
Journal: Gut (1982)

In five conscious dogs motility of the antrum, pyloric sphincter, and duodenum was recorded with strain gauge transducers and induction coils. Gastric evacuation of low, medium, and high viscosity meals was measured via a duodenal cannula and observed simultaneously by radiography. Computer analysis of the propagation of the gastric waves revealed increased velocity in the distal antrum but no simultaneous contractions of the terminal antrum and pyloric sphincter. Radiography showed, and measurements of the antral diameter confirmed, that the indentations of the gastric waves were significantly deeper with the low viscosity liquid meal compared with the medium and high viscosity meals. Thereby, retropulsion of the medium and high viscosity ingesta was produced. Results indicated that gastric evacuation was regulated predominantly by the depth of the peristaltic indentation, which depended on the viscosity of the gastric contents. Nothing indicated that the phasic contractions of the pyloric sphincter were of importance for the regulation of gastric emptying.
Reducing pain associated with injection of lignocaine
Authors: C. Dryden, R. Jackson, R. Alexander
Journal: BMJ (1992)

1. The alkaloidal product from the leaf of Solanum pseudocapsicum, L. has some toxicity and the minimum lethal doses for the frog, rabbit and cat are given. 2. The most marked effect is on the heart which is slowed by direct action on the muscle. Impulse formation at the pacemaker is slowed and there is marked retardation of conduction throughout the cardiac tissues. These effects are produced independently of the vagus. Larger and toxic doses cause ventricular fibrillation. 3. The substance produces insignificant effects on smooth muscle. 4. The main action, viz., on the heart, is the same as that produced by a dry alcoholic extract of the leaf.
Some Predict Increased Steroid Use in Sports Despite Drug Testing, Crackdown on Suppliers
Authors: Virginia Cowart
Journal: JAMA (1987)

NEITHER Charles Yesalis, PhD, nor MAJ James Wright, PhD, sees any drop-off in anabolic steroid use in athletes, and both expect it to increase in the immediate future, a different viewpoint than the one expressed by some other researchers ( JAMA 1987;257:421-423,427).  Yesalis is an epidemiologist at Pennsylvania State University, University Park, and Wright is an exercise physiologist with the US Army at Fort Benjamin Harrison, Indianapolis. They say that they have the impression most college football players don't want to take steroids, but many do because they believe that players on competing teams are using them. (Wright says the reasons football players give for using steroids are that their power output goes up and they can expect to recover faster from the physical punishment inherent in the sport.)  On the other hand, the two investigators say, most bodybuilders and power lifters do want to take steroids because they say it
Immunohistochemical evidence for differential distribution of 5α-reductase isoenzymes in human skin
Authors: W. EICHELER, M. DREHER, R. HOFFMANN, R. HAPPLE, G. AUMULLER
Journal: British Journal of Dermatology (1995)

Antibodies raised against fragments of synthetic peptides of human 5α‐reductase isoenzymes 1 (h5αrl) and 2 (h5αr2) were applied to paraffin sections of human skin (scalp, eyelid, lip, breast, scrotum). Immunoreactive sites were differentially distributed, in that h5αrl immunoreactivity was present in the nuclei of cells in the stratum germinativum (basal and lower portion of the spinous layer) of the epidermis, subepithelial tibroblasts, adipocytes, smooth muscle cells of the scrotal tunica dartos, basal cells of sebaceous glands, excretory duct cells of sweat glands, cells of the dermal papilla and fibrous and outer epithelial sheath of hair roots, as well as endothelial cells of small vessels and Schwann cells of cutaneous myelinated nerves. In contrast, immunoreactivity for h5αr2 was found in the cytoplasm of the cells of the spinous layer (and far less intensely in the basal layer) of the epidermis, subepidermal fibrocytes, and especially in subcutaneous adipocytes. Immunoreactivity was strongest in the non‐keratinized portion of the inner epithelial sheath and the cuticle of hair follicles, whereas other portions of the hair root were negative. Sweat glands were stained, whereas sebaceous glands showed only weak diffuse immunoreactivily. In mucoculaneous zones, salivary glands and conjunctival epithelium showed immunoreactive cells. Vascular endothelium displayed immunoreactivity only in the genital region. We present experimental evidence for a differential distribution of 5α‐reductase isoenzymes in human skin. This might reflect a diversity in the response of different areas of the skin to androgenic challenge.