tbuckley/cabot-search huggingface dataset:
Arrhythmogenic Action of Thrombin During Myocardial Reperfusion via Release of Inositol 1,4,5-Triphosphate
Authors: Alexander N. Jacobsen, Xiao-Jun Du, Kim A. Lambert, Anthony M. Dart, Elizabeth A. Woodcock
Journal: Circulation (1996)

Background Cardiac reperfusion initiates release of inositol 1,4,5-triphosphate [Ins(1,4,5)P 3 ] and arrhythmogenesis via norepinephrine stimulation of α 1 -adrenergic receptors. The present study examines arrhythmogenic effects of thrombin-stimulated Ins(1,4,5)P 3 release under these conditions. Methods and Results [ 3 H]Ins(1,4,5)P 3 release was measured in [ 3 H]inositol-labeled rat hearts by high-performance liquid chromatography. Arrhythmia studies were performed in buffer-perfused rat hearts. Two-minute reperfusion after 20 minutes of global ischemia increased [ 3 H]Ins(1,4,5)P 3 from 1123±77 to 2238±44 cpm/mg tissue. No increase was observed in catecholamine-depleted hearts (755±89 cpm/mg). The addition of thrombin (5 IU/mL) or thrombin receptor agonist peptide (TRAP 1-6 , 50 μmol/L) restored the reperfusion Ins(1,4,5)P 3 response (thrombin, 1518±68 cpm/mg and TRAP 1-6 , 1755±128 cpm/mg). Ins(1,4,5)P 3 release initiated by norepinephrine or thrombin was inhibited by gentamicin (150 μmol/L; 986±52 and 868±125 cpm/mg, respectively). The thrombin response was inhibited by the phospholipase C inhibitor U-73122 (5 μmol/L; 394±59 cpm/mg) but not by its inactive isomer U-73343. The norepinephrine response was not inhibited by U-73122 (2126±74 cpm/mg). Ventricular tachycardia and ventricular fibrillation were observed in intact hearts but not in hearts from catecholamine-depleted rats (ventricular fibrillation duration, 110±19 versus 0±0 seconds). The addition of thrombin or TRAP 1-6 increased arrhythmias in catecholamine-depleted hearts (112±32 and 89±28 seconds, respectively). Gentamicin and U-73122 but not U-73343 prevented thrombin-induced arrhythmias. Gentamicin inhibited norepinephrine-initiated arrhythmias, but U-73122 was ineffective. Conclusions This study demonstrates that the development of reperfusion arrhythmias under these conditions depends on the release of Ins(1,4,5)P 3 .
Hazard of Saline Abortion
Authors: Norman R. Kaplan
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The report of Gupta and Cohen (220:681,1972) of water intoxication associated with saline abortion can be added to the growing list of studies outlining the hazards of the procedure. Saline amniocentesis abortion has the highest fatality rate of any elective surgical technique, second only to cardiac transplantation. The ethical, sensible answer to this problem would be to place a moratorium on saline abortions even if we have to revert to hysterotomy for late abortions.
Surgical Decompression for Diabetic Sensorimotor Polyneuropathy
Authors: David R. Cornblath, Aaron Vinik, Eva Feldman, Roy Freeman, Andrew J.M. Boulton
Journal: Diabetes Care (2007)

Diabetic neuropathy remains an unmet medical need. While scientific advances (1,2) have been made in understanding pathophysiology, the impact on the clinical care of patients has been minimal, aside from symptomatic treatments for the pain that may accompany diabetic sensorimotor polyneuropathy (DPN) (3). Improved glucose control is still the main recommendation for the prevention and treatment of DPN, based on studies conducted over 10 years ago. Recently, two evidence-based reviews (4,5) for the treatment of diabetic neuropathy have been published, which form the basis of the subsequent American Diabetes Association position statement (6) on the topic.

Into the apparent void of therapy for DPN, surgical decompression of multiple lower or upper limb nerves is being advocated as the treatment (7). The procedure is being utilized to treat symptomatic and generalized DPN. This approach is based on a series of hypotheses. First, the signs and symptoms of DPN are due to multiple nerve entrapments. In the lower limb, foot numbness is ascribed to “entrapment” of the peroneal nerve at both the fibular head and the anterior tarsal tunnel, the tibial nerve in the tarsal tunnel, and the sural nerve in the distal posterior calf. In …
P177 Evolution of lung function in primary ciliary dyskinesia: a two centre retrospective study
Authors: M. Maglione, A. Bush, C. Hogg, S. Montella, F. Santamaria
Journal: Thorax (2011)

<h3>Background</h3> Evolution of spirometry in primary ciliary dyskinesia (PCD) and its determinants are unclear. To assess morbidity and burden of this condition, we investigated the progression of spirometry in patients from two European centres. <h3>Methods</h3> Ninety-six patients with =1 spirometry (Naples, Italy, n=21; London, UK, n=75) were enrolled. Sixty-five (Naples, n=15; London, n=50) with 4 years spirometry were analysed longitudinally. Best annual FEV<sub>1</sub>, corresponding FVC, both expressed as z-scores, and sputum culture results were recorded. <h3>Results</h3> In Naples and London, age at referral to the centre was 9.8 (range, 0.1–20.2) and 6.1 years (range, 0.1–17.3), respectively (p=0.02), while age at first spirometry was 11.6 (range, 8.1–20.2) and 8.4 years (range, 4.2–17.3), respectively (p&lt;0.001). In both centres patients with situs in versus (Naples, n=15; London, n=36) were referred earlier (p&lt;0.001). Despite later diagnosis, Naples children had better baseline FEV<sub>1</sub> and FVC z-scores (−0.53 (1.60) vs −1.66 (1.35), and 0.50 (1.55) vs −1.36 (1.32), p&lt;0.001 respectively) when first seen. Slopes of FEV<sub>1</sub> z-scores over 4 years were −0.05 (95% CI −0.36 to 0.26) and 0.05 (95% CI −0.05 to 1.65) in Naples and London, respectively (p=0.38). No significant correlation was found between slopes of FEV<sub>1</sub> z-scores and age at referral or baseline FEV<sub>1</sub> z-score. <i>Haemophilus influenzae</i> was the most frequently isolated pathogen (95% and 79% of subjects in Naples and London, respectively, p=0.1). Naples subjects had higher prevalence of <i>Pseudomonas aeruginosa</i> (62% vs 36%, p=0.04). <i>P aeruginosa</i> isolation was not associated with worse baseline FEV<sub>1</sub> z-scores or slopes of FEV<sub>1</sub> z-scores. <h3>Conclusions</h3> The better lung function despite later diagnosis in Naples is apparently unexplained. However, as spirometry in PCD is stabilised during treatment, its short-term evolution is not related to age at referral or to baseline FEV<sub>1</sub>. Spirometry is thus not a useful end-point for randomised controlled trials of treatment. Late diagnosis is common for patients without <i>situs</i> anomalies. Although the potential impact of <i>P aeruginosa</i> infection on PCD lung function is unclear, its unexpectedly high prevalence merits further study to determine best prevention and management strategies.
Case 46-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Peter M. Yurchak, James F. Southern
Journal: New England Journal of Medicine (1989)

Presentation or CaseA 52-year-old man was admitted to the hospital because of chest pain.There was a history of insulin-dependent diabetes mellitus for 20 years. In addition, he had a long history of hypertension and a more recent finding of hyperlipoproteinemia. Nine years before entry the patient was first admitted to this hospital because of chest pain, and an electrocardiogram showed an acute anterior myocardial infarct with Q waves in Leads V1 and V2. He experienced angina during convalescence, with ST-segment depressions in Leads 2, 3, and aVF, and during one episode of chest pain there . . .
Clinical implications. Biological coagulation findings in third-generation oral contraceptives
Authors: J Conard
Journal: Human Reproduction Update (1999)

An increased risk of venous thrombosis has been demonstrated in women receiving oral contraceptives (OCs). This risk has been primarily associated with the oestrogen content, but recent studies showed that the progestogen may also plays a role. A higher risk was found with the so-called third-generation (desogestrel, gestodene) as compared with the second-generation progestogens (levonorgestrel). The risk was approximately two-fold. These unexpected results have been the subject of many debates, and bias-such as selection bias-has been suggested. The existence of bias cannot be completely excluded, but the thrombotic risk seems however to be slightly higher with the third-generation progestins. Haemostatic changes have been observed during OC intake. Both coagulation and fibrinolytic activity are increased: the beneficial profibrinolytic effect may counterbalance the deleterious procoagulant effect. This may explain the absolute risk of venous thromboembolism is low during OC treatments. Some women who have pre-existing haemostatic abnormalities such as deficiency in antithrombin or activated protein C resistance with factor V Leiden, may be at a higher risk. Theoretically, this could be due to an increased coagulation or to a lack of increased fibrinolysis as compared with second-generation progestogens. The only difference presently reported with third-generation OCs is a decreased sensitivity to activated protein C, possibly resulting in hypercoagualibility of greater magnitude. The selection bias suggested in epidemiological studies may also exist for the later study, as women taking third- or second-generation OCs were not randomized. The possible increased risk related to third-generation OCs should not change the known general contra-indication. Practical guidelines are proposed for women with personal or family history of venous thromboembolism, and for those with a congenital cause of thrombophilia.
Zimbabwe set to outlaw human rights organisations
Authors: Caroline White
Journal: BMJ (2004)

A new bill, which would criminalise non-governmental organisations working to promote human rights and ban overseas agencies from funding local groups, is set to become law in Zimbabwe before the end of the year.

The bill, which had its final reading last week, is being viewed as a further attempt to silence potential opponents of President Robert Mugabe's ruling Zanu-PF party, ahead of the country's elections in March 2005.

In The Zimbabwe Independent last week, public service and welfare minister Paul Mangwana reportedly denied claims that the bill deliberately targeted specific organisations, describing the idea of a …
Letter: Aetiology of anencephaly and spina bifida.
Authors: B Field, C Kerr
Journal: BMJ (1976)

dying of coeliac disease and Addison's disease showed lymphocytes, mononuclear cells, and giant cells in her fibrotic adrenal glands; it is likely that she had sarcoidosis initially because she had earlier shown generalised lymphadenopathy and erythema nodosum.5 Five patients with sarcoidosis had adrenal failure," and it is interesting that coeliac disease is also occasionally associated with active tubercu- losis.7Chronic changes only were seen in the lung biopsy in the case described by Dr J Cummiskey and his colleagues (5 June, p 1401), and the immune response had faded after four years.But the pulmonary inflammation was still active in other reported cases.Three patients whose lungs were biopsied showed non-caseating granulomas.One of them, biopsied percutaneously by Mr M Meredith- Brown, had a positive Mantoux test, a calcified ring-shadow in the same lung, and bilateral apical scars.She also showed the cell-mediated immunity which is found in sarcoidosis, Crohn's disease, and BCG non-reactors."The syndrome may have therefore been caused by sarcoidosis in these three cases, and in one other.9The sarcoid agent may be a cause of "extrinsic alveolitis," but earlier and wider investigation of such cases is needed to prove this point.
F-18 FDG PET/CT Provides the Earliest Findings of Enthesitis in Reactive Arthritis
Authors: Yoshinori Taniguchi, Yoshitaka Kumon, Syuichi Nakayama, Kaoru Arii, Takenao Ohnishi, Yasuhiro Ogawa, Shigeto Kobayashi, Yoshio Terada
Journal: Clinical Nuclear Medicine (2011)

A 31-year-old woman developed polyarthralgia and extension disorder of the right elbow of 2 months' duration without abdominal symptom. Laboratory findings revealed C-reactive protein 2.7 mg/dL. Anti-nuclear antibody (ANA), rheumatoid factor (RF), and anti-cyclic citrullinated peptide (CCP) antibody were negative. F-18 FDG PET/CT showed elevated pinpoint uptakes of FDG in the entheses. In contrast, MRI revealed no specific findings. Four months after PET/CT, she developed right lower abdominal pain. Colonoscopy showed abscess in ascending colon, which the initial PET/CT finding might mean early image of infective colitis. A diagnosis of early reactive arthritis was made. Treatment with antibiotics improved colitis, colonic abscess, and enthesitis after 2 months. Moreover, F-18 FDG PET/CT showed no accumulation in colon and entheses. These findings suggest that F-18 FDG PET/CT scanning allows enthesitis in the early stage of reactive arthritis, before the possible detection by the other procedures.
P668 SERUM INTERLEUKIN 9 LEVEL AS A PREDICTIVE MARKER OF SPONTANEOUS SEROCLEARANCE OF HEPATITIS B SURFACE ANTIGEN IN CHRONIC HEPATITIS B PATIENTS
Authors: H.-I. Yang, M.-H. Lee, J. Liu, Y.-C. Chien, H.-Y. Chen, C.-J. Liu, C.-L. Jen, R. Batrla-Utermann, C.-J. Chen
Journal: Journal of Hepatology (2014)
Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia
Authors: E Ellinghaus, M Stanulla, G Richter, D Ellinghaus, G te Kronnie, G Cario, G Cazzaniga, M Horstmann, R Panzer Grümayer, H Cavé, J Trka, O Cinek, A Teigler-Schlegel, A ElSharawy, R Häsler, A Nebel, B Meissner, T Bartram, F Lescai, C Franceschi, M Giordan, P Nürnberg, B Heinzow, M Zimmermann, S Schreiber, M Schrappe, A Franke
Journal: Leukemia (2011)

Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells. The etiology of ALL is believed to be multifactorial and likely to involve an interplay of environmental and genetic variables. We performed a genome-wide association study of 355 750 single-nucleotide polymorphisms (SNPs) in 474 controls and 419 childhood ALL cases characterized by a t(12;21)(p13;q22) — the most common chromosomal translocation observed in childhood ALL — which leads to an ETV6–RUNX1 gene fusion. The eight most strongly associated SNPs were followed-up in 951 ETV6-RUNX1-positive cases and 3061 controls from Germany/Austria and Italy, respectively. We identified a novel, genome-wide significant risk locus at 3q28 (TP63, rs17505102, PCMH=8.94 × 10−9, OR=0.65). The separate analysis of the combined German/Austrian sample only, revealed additional genome-wide significant associations at 11q11 (OR8U8, rs1945213, P=9.14 × 10−11, OR=0.69) and 8p21.3 (near INTS10, rs920590, P=6.12 × 10−9, OR=1.36). These associations and another association at 11p11.2 (PTPRJ, rs3942852, P=4.95 × 10−7, OR=0.72) remained significant in the German/Austrian replication panel after correction for multiple testing. Our findings demonstrate that germline genetic variation can specifically contribute to the risk of ETV6–RUNX1-positive childhood ALL. The identification of TP63 and PTPRJ as susceptibility genes emphasize the role of the TP53 gene family and the importance of proteins regulating cellular processes in connection with tumorigenesis.
Abstract P4-04-01: Understanding estrogen receptor transcription in breast cancer
Authors: JS Carroll
Journal: Cancer Research (2013)

Abstract Estrogen Receptor (ER) is the defining feature of luminal breast cancers, where is functions as a transcription factor. The traditional view of ER getting recruited to promoters of target genes is too simplistic. The recent discovery of ER-DNA interaction regions from ER+ breast cancer cell lines has revealed that ER rarely associates with promoter regions of target genes and instead associates with enhancer elements significant distances from the target genes. The genomic mapping of ER binding events also revealed the enrichment of DNA motifs for Forkhead factors. The Forkhead protein FOXA1 (HNF3a) was subsequently shown to bind to half of the ER binding events in the genome and was required for ER to maintain interaction with DNA. We have extended on these findings to explore ER and FoxA1 functional interactions in breast cancer, with a specific focus on changes in binding dynamics that occur during endocrine resistance. To this end, we have established transcription factor mapping approaches (ChIP-seq) in primary tumor material, to investigate differential ER/FoxA1 binding that occurs during tumor progression. We have functionally explored underlying factors that contribute to altered transcription factor binding and activity. In addition, we have recently established a method for rapid unbiased discovery of protein interactomes, which we have applied to discover ER and FoxA1 associated proteins. We find unexpected interactions between ER and additional nuclear receptors in ER+ breast cancer, which appear to be important modulators of cellular growth and endocrine response. These findings help delineate the complexes that influence ER transcriptional activity and ultimately impinge on tumor progression and drug sensitivity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-04-01.
512 Entecavir (ETV) demonstrates consistent responses throughout baseline disease and demographic subgroups for the treatment of lamivudine-refractory HBeAg(+) patients with chronic hepatitis B
Authors: C. Yurdaydin, H. Senturk, A. Boron-Kaczmarska, M. Raptopoulou-Gigi, Y. Batur, Z. Goodmans, J. Vaughah, H. Brett-Smith, R. Hindes
Journal: Journal of Hepatology (2006)
Book Review Neuromuscular Function and Disease: Basic, Clinical, and Electrodiagnostic Aspects Edited by William F. Brown, Charles F. Bolton, and Michael J. Aminoff. 1948 pp., illustrated, in two volumes. Philadelphia, W.B. Saunders, 2002. $395. 0-7216-8922-1
Authors: Tulio E. Bertorini
Journal: New England Journal of Medicine (2003)
Alleged Army Medical Abuse.
Authors: Charles Smart
Journal: JAMA (1900)

Washington, D. C., August 21, 1900. <h3>To the Editor:</h3> —We have been reading recently in the daily press and medical journals about the shortcomings of the British Army Medical Department in Southern Africa. During the active progress of the war we heard nothing but words of praise for the devotion to duty of the Medical Department and its foresight in providing all that was needful for the care of the wounded hundreds of miles from the base of supplies. General officers, themselves wounded, testified to the admirable management which brought their wounded men from the field and transported them in comfort to the base hospitals at Cape Town. Kipling has told the story of one hospital train on its way to the front and thence back to the general hospitals with its load of disabled men. His brilliant description of the return trip conveys a sense of the restfulness and
Multicentric Angiofollicular Lymph Node Hyperplasia with Peripheral Neuropathy, Pseudotumor Cerebri, IgA Dysproteinemia, and Thrombocytosis in Women
Authors: John M. Feigert
Journal: Annals of Internal Medicine (1990)

Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.
Nephropathic Cystinosis — A Gap between Developing and Developed Nations
Authors: Aurelia Bertholet-Thomas, Justine Bacchetta, Velibor Tasic, Pierre Cochat
Journal: New England Journal of Medicine (2014)

This letter discusses therapeutic disparities between developing countries and developed countries for patients with nephropathic cystinosis, one of a number of rare diseases for which therapy exists but is unevenly distributed.
The clinical significance of changes in genetic heterogeneity of the hypervariable region 1 in chronic hepatitis C with interferon therapy
Authors: M Shindo, K Hamada, S Koya, K Arai, Y Sokawa, T Okuno
Journal: Hepatology (1996)

We examined changes in the hypervariable region 1 of the hepatitis C virus (HCV) RNA that occurred with interferon therapy in 33 patients with chronic hepatitis C to assess the clinical significance of this region. The 33 patients had HCV genotype 1b and were classified into three groups based on serum aminotransferase levels during and after therapy with alpha interferon; long-term responders (n = 9), short-term responders (n = 11), and nonresponders (n = 13). Changes in the genetic heterogeneity of the hypervariable region 1 were determined by using nonisotopic polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). HCV RNA levels were evaluated by reverse transcriptase PCR and branched DNA probe assays. Changes in sequences were determined by cloning and sequencing analysis. Before therapy, the long-term responders had significantly lower degrees of heterogeneity and lower viral levels than nonresponders. There were no significant differences between short-term and nonresponders. With interferon therapy, viral levels and degree of heterogeneity decreased to a greater extent among long-term and short-term responders than among nonresponders. Sequencing analysis showed that the three groups had similar clone numbers initially, but long-term responders had rather homogeneous viral populations, whereas short-term and nonresponders had heterogeneous populations, but that there were no nucleotide sequences or amino acid alignments that were specific for any group before, during, and 6 months after therapy. Approximately half of short-term and nonresponders received a second course of interferon 7 to 10 months after the initial therapy; all showed an identical response to the second course of therapy regardless of interim changes in the heterogeneity of hypervariable region 1. These findings suggest that (1) patients who were nonresponders or short-term responders had mixed viral populations that had differing sensitivities to interferon, (2) the changes in the hypervariable region 1 (HVR 1) did not affect responsiveness to interferon, and (3) the lower heterogeneity in the HVR 1 was associated with a long-term response to interferon only when the viral levels were low.