tbuckley/cabot-search huggingface dataset:
Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B
Authors: Amit C. Nathwani, Ulreke M. Reiss, Edward G.D. Tuddenham, Cecilia Rosales, Pratima Chowdary, Jenny McIntosh, Marco Della Peruta, Elsa Lheriteau, Nishal Patel, Deepak Raj, Anne Riddell, Jun Pie, Savita Rangarajan, David Bevan, Michael Recht, Yu-Min Shen, Kathleen G. Halka, Etiena Basner-Tschakarjan, Federico Mingozzi, Katherine A. High, James Allay, Mark A. Kay, Catherine Y.C. Ng, Junfang Zhou, Maria Cancio, Christopher L. Morton, John T. Gray, Deokumar Srivastava, Arthur W. Nienhuis, Andrew M. Davidoff
Journal: New England Journal of Medicine (2014)

In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose–response relationship, and the level of persistent or late toxicity.
The effectiveness of a preconditioning program on the incidence of running-related injuries in female novice runners: a randomised controlled trial
Authors: S Zijlstra, I Buist, S W Bredeweg
Journal: British Journal of Sports Medicine (2011)

Background The incidence of running-related injuries (RRI) in (female) novice runners is high. Preconditioning programs have shown to be effective on the incidence of sports and overuse injuries in different populations. Objective Is a preconditioning program effective for preventing RRIs in female novice runners? Design The prospective study is a large 2-arm randomised clinical trial. Participants were randomly assigned to a preconditioning group and a control group. Stratification for current sporting activities status, previous injury, and gender was applied. Setting Female novice runners preparing for a recreational 4-mile running event. Participants Healthy female novice runners (age 18–65), who had not sustained an injury of the lower extremity in the last 3 months and who had not been running on a regular basis in the previous 12 months. After randomisation 283 participants (mean age=36, mean body mass index=23) were allocated to the intervention group or the control group. Finally 113 participants in the intervention group and 126 in the control group were included for analyses. Interventions 4-week preconditioning program, in which the biomechanical load was gradually increased on the lower extremity with functional activities like hopping in place and walking. The program was directly followed by a 9-week running program for both groups. Main outcome measurements The primary outcome measure was RRIs per 100 runners. An RRI was defined as any musculoskeletal complaint of the lower extremity or back causing a restriction of running for at least 1 week. Results 15% (19 of 126) of the runners in the preconditioning group and 13% (15 of 113) of the control group sustained a RRI. This difference was not significant (÷2=0.16, df=1, p=0.69). Conclusion The preconditioning program did not have an effect on the incidence of RRIs in female novice runners.
Pressor effects of thyrotrophin releasing hormone during thyroid function testing.
Authors: E Rosenthal, Y C Najm, M N Maisey, P V Curry
Journal: BMJ (1987)

CommentThis study is the first to report pressor effects after the administration of 200 jIg thyrotrophin releasing hormone.4The short duration of the response may account for the previous failure to show such effects by non-invasive methods.Nausea often occurs during testing with thyrotrophin releasing hormone and may offset some of the pressor effects.None of our patients experienced nausea, presumably because of the amount of premedication, though this itself may have affected the degree of the response.The premedication allowed stable baseline readings, and the absence of nausea and retching allowed clean pressure traces.The mechanism of the pressor effects is uncertain: raised catecholamine
Effect of varying perfusion pressures on the output of sodium and renin and the vascular resistance in kidneys of rats with "post-salt" hypertension and Kyoto spontaneous hypertension.
Authors: L Tobian, M A Johnson, J Lange, S Magraw
Journal: Circulation Research (1975)

Isolated kidneys from both "post-salt" normotensive and hypertensive rats were perfused with blood from donor rats at varying pressures. At 130 mm Hg inflow pressure 15 "post-salt normotensive" kidneys put out 0.75 muEq Na/min/g kidney while 14 "post-salt hypertensive" kidneys put out 0.28 mu-Eq Na/min/g (P less than 0.001), a 63% reduction. They also put out 55% less water (P less than 0.002). Thus, if "hypertensive" kidneys are perfused at normal pressures, they put out subnormal amounts of Na and H-2-O. Such Na and H-2-O retention maintains the hypertensive state. Normal Na output in these kidneys was only reached at hypertensive (160) inflow pressures. This shift in the "pressure natriuresis" curve explains in part how some "hypertensive" kidneys maintain hypertension. These "hypertensive" kidneys have grossly abnormal autoregulation curves, each increment of pressure actually producing progressively greater increments of blood flow. Isolated kidneys from Kyoto hypertensive and normotensive rats showed no difference in Na and H-2-O excretion at 130 mm Hg inflow pressure. Thus, a tendency to Na retention demonstrable in the isolated kidney is apparently not supporting Kyoto hypertension. Moreover, isolated kidneys form Kyoto hypertensive rats released significantly lower amounts of renin at all levels of inflow pressure, averaging a 70% lower rate than Kyoto normotensive kidneys (P less than 0.01). Hence, Kyoto hypertension is not supported by a supernormal renin release inherent in the kidney. One can speculate that Kyoto hypertensive rats normally have an elevated sympathetic tone which stimulates release of renin. The denervation which occurs in isolating kidneys might therefore produce a proportionally greater percentage loss of sympathetic influence in these kidneys, which could possibly account for some of their reduced renin release. These Kyoto hypertensive kidneys are apparently not "reset" to maintain hypertension with either Na or renin.
Early Detection of Bone Marrow Involvement in Extramedullary Plasmacytoma by Whole-Body F-18 FDG Positron Emission Tomography
Authors: TAKASHI KATO, ERIKO TSUKAMOTO, TAKESHI NISHIOKA, AKIRA YAMAZAKI, HIROSHI SHIRATO, SUMIKO KOBAYASHI, MASAHIRO ASAKA, MASAHIRO IMAMURA, NAGARA TAMAKI
Journal: Clinical Nuclear Medicine (2000)

The utility of positron emission tomography (PET) with the glucose analog 2-deoxy-2-[F-18] fluoro-D-glucose (F-18 FDG) in plasmacytoma has not been well evaluated. The authors report a case of extramedullary plasmacytoma (EMP) in which whole-body F-18 FDG PET was useful in the early detection of bone marrow involvement. A 34-year-old woman had EMP without histologic or radiologic evidence of bone lesions. However, the early phase of bone marrow involvement was considered because of spotty accumulation shown by F-18 FDG PET. A follow-up F-18 FDG PET study after radiotherapy showed intense multifocal accumulation in the bone marrow, which was confirmed on bone marrow aspiration as abnormal proliferation of plasma cells. Whole-body F-18 FDG PET has the potential to detect the early phase of bone marrow involvement in patients with EMP.
Testing Poor Pregnant Women for Cocaine — Physicians as Police Investigators
Authors: G J Annas
Journal: New England Journal of Medicine (2001)

In 1989, Supreme Court Justice Thurgood Marshall surmised that “declaring a war on illegal drugs is good public policy . . . [but] the first, and worst, casualty of war will be the precious liberties of our citizens.”1 The same year, in the midst of President George Bush's “war on drugs,” the Medical University of South Carolina initiated a program to screen selected pregnant patients for cocaine and to provide positive test results to the police.2 At a time of high public concern about “cocaine babies,” this program seemed reasonable to the university and local public officials. Drug-screening programs in . . .
HSV Delivery of a Ligand-regulated Endogenous Ion Channel Gene to Sensory Neurons Results in Pain Control Following Channel Activation
Authors: James R Goss, Michael Cascio, William F Goins, Shaohua Huang, David M Krisky, Richard J Clarke, Jon W Johnson, Hitoshi Yokoyama, Naoki Yoshimura, Michael S Gold, Joseph C Glorioso
Journal: Molecular Therapy (2010)

Persistent pain remains a tremendous health problem due to both its prevalence and dearth of effective therapeutic interventions. To maximize pain relief while minimizing side effects, current gene therapy-based approaches have mostly exploited the expression of pain inhibitory products or interfered with pronociceptive ion channels. These methods do not enable control over the timing or duration of analgesia, nor titration to analgesic efficacy. Here, we describe a gene therapy strategy that potentially overcomes these limitations by providing exquisite control over therapy with efficacy in clinically relevant models of inflammatory pain. We utilize a herpes simplex viral (HSV) vector (vHGlyRα1) to express a ligand-regulated chloride ion channel, the glycine receptor (GlyR) in targeted sensory afferents; the subsequent exogenous addition of glycine provides the means for temporal and spatial control of afferent activity, and therefore pain. Use of an endogenous inhibitory receptor not normally present on sensory neurons both minimizes immunogenicity and maximizes therapeutic selectivity.
Abstract 2595: Screening for genomic rearrangements in <i>BRCA1</i> and <i>BRCA2</i> genes in Algerian breast/ovarian cancer families
Authors: Farid Cherbal, Nadjet Salhi, Rabah Bakour, Saida Adane, Kada Boualga, Philippe Maillet
Journal: Cancer Research (2012)

Abstract Background: Breast cancer is the leading cause of cancer death in women in Algeria. To date, few molecular genetics studies of BRCA1 and BRCA2 germline mutations have been reported in the Algerian population. The most frequent mutations encountered in BRCA genes are deletions or insertions of a few bases or single-base substitutions that result in premature stop codons. However, an increasing number of large genomic rearrangements (LGRs) have been identified especially in BRCA1 gene, whereas the frequency of genomic rearrangements in BRCA2 gene is low in many populations. The objective of our study was to characterize genomic rearrangements in 76 Algerian breast/ovarian cancer patients and relatives tested negative for small point mutations in BRCA1 and BRCA2 genes. Methods: MLPA was performed on genomic DNA as described by Schouten et al (2002). Screening for genomic rearrangements in BRCA1 and BRCA2 genes of 76 patients and relatives were performed by using MLPA commercial kits P002-B1, P087-B1 and PO45-B2, PO90-B2 respectively (MRC-Holland, Amsterdam, The Netherlands). To confirm the rearrangement and to determine the exact site of its genomic breakpoints, we performed long-range PCR of genomic DNA using the Expand Long Template PCR System (Roche Diagnostics GmbH, Mannheim, Germany). Results: MLPA analysis of the BRCA1 gene revealed two germline alterations in two unrelated patients among 76. A novel deletion of BRCA1 exon 2 (c.-19-α_80+−del/p.α) and a novel genomic breakpoint in deletion of BRCA1 exon 8 (c.442-α_547+−del/p≤) were identified in two patients with breast/ovarian cancer and bilateral breast cancer, respectively. No LGRs were detected in BRCA2 gene. We found by using Long range PCR technique that our patient with the BRCA1 exon 8 deletion is heterozygous for a 2.6 kb deletion. Investigations aimed at determining the genomic breakpoint of the BRCA1 exon 2 deletion described in our study is on going. Conclusion: For the first time, we report here two genomic rearrangements in BRCA1 gene in Algerian breast/ovarian cancer patients. Our results reinforce the idea that breast/ovarian cancer families tested negatively for small point mutations should be routinely screened with MLPA for large genomic rearrangements in BRCA1 and BRCA2 genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2595. doi:1538-7445.AM2012-2595
Nur Fiona Onen Albring
Authors: A. Onen
Journal: BMJ (2015)

Nur Fiona Onen Albring was born in Izmir, Turkey, with her identical twin sister on 17 December 1975. They were the much loved daughters of a Scottish mother and Turkish father. Nur was born with large congenital melanocytic naevi. When the twins were 4, the family moved to Scotland, so Nur could undergo numerous pioneering operations to remove some of her moles at Canniesburn Hospital, Glasgow. This experience instilled a strong desire in her to become a doctor, something she worked hard to achieve, graduating at the age of 23, from Glasgow University with a MBChB and BSc in microbiology (with commendation).

After completing her preregistration year as a junior house officer in Glasgow, Nur travelled to New South Wales in Australia. There she spent two years completing further training in emergency medicine, paediatrics, obstetrics and gynaecology, and health promotion and addiction …
Pigeon fancier's lung
Authors: S. Bourke, G. Boyd
Journal: BMJ (1997)

Pigeon racing is based on the remarkable homing instinct of pigeons, which enables them to return to their loft over distances of many hundreds of miles. British pigeon fanciers are particularly proud of their role in the second world war, when highly trained pigeons were used for communication.1 Pigeons were parachuted in small containers into occupied Europe with instructions for the finder to attach espionage messages to the birds, which were then released to fly silently and undetected back to lofts in Britain.

There are now about 83 000 registered pigeon fanciers in Britain. When racing, the birds are transported to a liberation point; a ring is placed on one leg; and, when released, the bird returns to its loft, where the ring is removed and placed in a special clock which registers the exact “timing in” of the bird. The location of each loft has been registered so that the distance travelled by each pigeon can be calculated. Racing pigeons have been bred and trained for speed and endurance. The official British duration record is 1173 miles in 15 days, and the highest race speed is 110.07 miles per hour.2 Although a typical pigeon fancier keeps pigeons as a hobby, pigeon fancying is a multimillion pound business, and top class birds have been sold for as much as £110 800.2

Pigeon fancier's lung …
Comparison of homozygous sickle cell disease in Northern Greece and Jamaica
Authors: J. Christakis, H. Hassapopoulou, M. Papadopoulou, K. Mandraveli, N. Vavatsi, D. Loukopoulos, J.S. Morris, B.E. Serjeant, G.R. Serjeant
Journal: The Lancet (1990)
Six-Year Outcome of Cognitive Behavior Therapy for Prevention of Recurrent Depression
Authors: Giovanni A. Fava, Chiara Ruini, Chiara Rafanelli, Livio Finos, Sandra Conti, Silvana Grandi
Journal: American Journal of Psychiatry (2004)

A paucity of studies use nonpharmacological strategies for preventing recurrence in depression. Cognitive behavior treatment of residual symptoms was found to yield a significantly lower relapse rate than clinical management in recurrent depression at a 2-year follow-up. The objective of this investigation was to provide a 6-year follow-up of cognitive behavior treatment versus clinical management.Forty patients with recurrent major depression who had been successfully treated with antidepressant drugs were randomly assigned to either cognitive behavior treatment of residual symptoms (supplemented by lifestyle modification and well-being therapy) or clinical management. In both groups, antidepressant drugs were tapered and discontinued. A 6-year follow-up was undertaken. During this period, no antidepressant drugs were used unless a relapse ensued.Cognitive behavior treatment resulted in a significantly lower relapse rate (40%) at a 6-year follow-up than did clinical management (90%). When multiple recurrences were considered, the group that received cognitive behavior treatment had a significantly lower number of relapses in comparison with the clinical management group.The results suggest that the sequential use of cognitive behavior treatment after pharmacotherapy may improve the long-term outcome in recurrent depression. A significant proportion of patients with recurrent depression might be able to withdraw from medication successfully and to stay well for at least 6 years with a focused course of psychotherapy.
Gender and Age Differences in the Perception of Bother and Health Care Seeking for Lower Urinary Tract Symptoms: Results from the Hospitalised and Outpatients’ Profile and Expectations Study
Authors: Apostolos Apostolidis, Paraskevi-Sofia Kirana, Gretchen Chiu, Carol Link, Marina Tsiouprou, Dimitrios Hatzichristou
Journal: European Urology (2009)
Buthionine sulfoximine treatment impairs rat diaphragm function.
Authors: C F Morales, A Anzueto, F Andrade, J Brassard, S M Levine, L C Maxwell, R A Lawrence, S G Jenkinson
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Activation of the glutathione (GSH) redox cycle with production of glutathione disulfide (GSSG) has been shown to occur in the diaphragm during inspiratory resistive loading (RB). Buthionine sulfoximine (BSO) lowers tissue GSH by irreversibly inhibiting the rate-limiting synthesis enzyme gamma-glutamylcysteine synthetase. We investigated the effects of BSO on rat diaphragm function, both at rest and after a period of RB. Rats in the RB groups underwent inspiratory RB until they were unable to sustain 70% of their maximal airway pressure. A portion of the diaphragm was analyzed for GSH and GSSG levels, and measurements of in vitro contractile properties included contraction times, maximal tetanic tension (Po), maximal twitch tension (Pt), and force frequency curves. BSO treatment produced a profound depletion of diaphragmatic GSH. Neither BSO nor RB alone significantly altered diaphragm contractile properties at this load of RB. But, in BSO-RB rats, there was a significant decrease in Pt, Po, and tetanic tension at all frequencies of stimulation compared with those in other groups. These data reveal that animals treated with BSO followed by inspiratory resistive loading exhibit marked diaphragm impairment, suggesting that GSH may play an important role in protecting the diaphragm from the stress induced by this resistive breathing protocol.
Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations
Authors: Wen-Chien Chou, Huai-Hsuan Huang, Hsin-An Hou, Chien-Yuan Chen, Jih-Luh Tang, Ming Yao, Woei Tsay, Bor-Sheng Ko, Shang-Ju Wu, Shang-Yi Huang, Szu-Chun Hsu, Yao-Chang Chen, Yen-Ning Huang, Yi-Chang Chang, Fen-Yu Lee, Min-Chih Liu, Chia-Wen Liu, Mei-Hsuan Tseng, Chi-Fei Huang, Hwei-Fang Tien
Journal: Blood (2010)
An International Service Corps for Health — An Unconventional Prescription for Diplomacy
Authors: Vanessa Bradford Kerry, Sara Auld, Paul Farmer
Journal: New England Journal of Medicine (2010)

At first glance, medicine may seem unrelated to foreign policy, but in reality it is an unappreciated partner of diplomacy. In many parts of the world, poverty, inequity based on ethnicity or sex, shoddy public infrastructure, and environmental degradation have resulted in poor health as well as political and social instability. Poor health, in turn, fuels social vulnerabilities and discord, as illness diminishes productivity and disrupts family and social structures. The United States, a major funder of global health initiatives, has an opportunity to change the way it helps to tackle these challenges by investing in local health systems, equitable . . .
Primary Tracheal Non-Hodgkin's Lymphoma
Authors: Mackenzie L. Luick, Eric K. Hansen, Mathew S. Greenberg, Robert Kim, Michael Owens, Christie J. Moore, Mona Flores
Journal: Journal of Clinical Oncology (2010)

A 66-year-old woman presented as an outpatient with progressive dyspnea on exertion from September to October 2009.She had no cough or hemoptysis.An initial chest x-ray on September 9, 2009, was normal.In October, her symptoms worsened, and she developed wheezing and stridor during exertion.She denied fever and night sweats, but she did report weight loss of 45 pounds from December 2008 to May 2009.She also had decreased sensation in her lower extremities as a result of recently diagnosed chronic inflammatory demyelinating polyneuropathy (CIDP), for which she was receiving monthly intravenous immunoglobulin.She had no other complaints.Her medical history included gastroesophageal reflux and hypothyroidism.She was a lifelong nonsmoker.On examination, she appeared comfortable at rest, but stridor was present during minimal activity.Vital signs and oxygen saturation A B C Before radiotherapy 7 d after radiotherapy Fig 1.
Visualization of Residual Splenic Tissue
Authors: MILAN S. ANDRUS, GERALD S. JOHNSTON
Journal: Clinical Nuclear Medicine (1981)

Routine liver–spleen imaging is sometimes performed to search for residual splenic activity following splenectomy. A patient with previous splenectomy following trauma snowed no evidence of splenic tissue when the usual technique was used for colloidal liver–spleen imaging. A repeat study with an increased intensity setting demonstrated multiple sites of residual splenic tissue in the abdomen.
L-type cardiac calcium channels in doxorubicin cardiomyopathy in rats morphological, biochemical, and functional correlations.
Authors: E C Keung, L Toll, M Ellis, R A Jensen
Journal: Journal of Clinical Investigation (1991)

Doxorubicin (DXR) is an effective antitumor agent in a wide spectrum of neoplasms. Chronic treatment is associated with cardiomyopathy and characteristic myocardial ultrastructural changes, which include swelling of the t tubules. Accordingly, we investigated excitation-contraction coupling in cardiomyopathic rat heart resulting from chronic DXR treatment. Using the whole-cell patch clamp technique, we studied the L-type calcium channel in single cells enzymatically isolated from normal (CTRL) and DXR rat hearts. Despite similar cell dimensions, the total membrane capacitance was significantly smaller in the DXR cells (138 +/- 9 pF) than in the CTRL cells (169 +/- 11 pF) (mean +/- SEM, n = 9, P less than 0.05). The mean current and the current density-voltage relationships of the CTRL and the DXR cells were significantly different (n = 9, P less than 0.001) with the maximal peak L-type calcium current (ICa) density increased from 6.4 +/- 0.9 in CTRL cells to 10.5 +/- 2.4 microA/cm2 in the DXR cells (P less than 0.05). There was no shift either in the current-voltage relationship or the steady-state inactivation curve in the two cell groups. However, the fast time constant of inactivation was increased at a membrane voltage of -10 to 10 mV. Calcium channel antagonist equilibrium binding assays using [3H]-PN200-110 revealed no difference in the maximal receptor binding capacity (CTRL, 194 +/- 27 and DXR 211 +/- 24 fmol/mg protein; P greater than 0.05, n = 6) and in receptor affinity (CTRL, 0.15 +/- 0.05 and DXR 0.13 +/- 0.03 nM; P less than 0.05). These data suggest that a decrease in effective capacitance might be associated with t-tubular damage. Despite this decrease, ICa was increased in the DXR cells. Such an increase may result from an alteration in the properties of the calcium channels and/or recruitment of "hibernating" channels in the remaining surface and t-tubular membranes.
Diabetes mellitus and outcome after primary coronary angioplasty for acute myocardial infarction: lessons from the GUSTO-IIb angioplasty substudy
Authors: David Hasdai, Christopher B Granger, S.Sanjay Srivatsa, Douglas A Criger, Stephen G Ellis, Robert M Califf, Eric J Topol, David R Holmes
Journal: Journal of the American College of Cardiology (2000)