tbuckley/cabot-search huggingface dataset:
Antithrombotic Effect of Monamine Oxidase Inhibitor (Nialamide)
Authors: Takio Shimamoto, Tadao Ishioka, Tsutomu Fujita
Journal: Circulation Research (1962)

A new type of antithrombotic substance, nialamide, was compared with phenindione and warfarin in its preventive effect against experimental thrombosis produced in rabbits. One hundred fifty-seven rabbits were subjected to quantitative traumatization of the endothelial surface of the retroauricular artery and marginal vein of the ear. Pretreatment of animals with 3 to 5 mg./Kg. of nialamide, which did not prolong the one-stage prothrombin time, was much more effective in preventing thrombosis than either phenindione or warfarin, both of which prolonged the prothrombin time markedly. Even in the animals pretreated by 600 to 900 mg. of phenindione, which reduced the prothrombin activity to less than 6 per cent, the preventive effect of phenindione is significantly less than the antithrombotic effect of 3 to 5 mg./Kg. of nialamide. Pretreatment of animals with 1.5 mg./Kg. of nialamide was found to be ineffective. However, the concomitant application of subeffective doses of both phenindione, 150 mg., and nialamide, 1.5 mg., was found to be effective. On the other hand, the addition of phenindione, even in doses as large as 300 to 900 mg., to an effective dose of nialamide, 3 to 5 mg./Kg., did not further enhance the antithrombotic effect of nialamide. The antithrombotic effect of nialamide was not shown to be significantly modified by sympathectomy or by denervation of the blood vessels tested. Nialamide was found to prevent the aggregation of platelets on the injured endothelial surface.
Abstract LB-236: Identifying novel kinase fusions via targeted DNA capture and next-generation sequencing
Authors: Juliann Chmielecki, Martin Peifer, Agnes Viale, Nicolas Socci, Peilin Jia, Zhongming Zhao, Roman Thomas, William Pao
Journal: Cancer Research (2011)

Abstract Tyrosine kinase (TK) fusion proteins result from genomic rearrangements that juxtapose TK signaling domains with various upstream partners. Since tumor cells can become dependent upon the resultant constitutive kinase activity for tumorigenesis and survival, TK fusions serve as attractive targets for anti-cancer therapy. In the past, identification of TK fusions in cancers has been hindered by experimental techniques that lack sufficient sensitivity and throughput. To overcome these challenges, we developed a screen to systematically identify TK fusions in tumor DNA based upon observed conservation of genomic fusion breakpoints. The approach involves selective capture of regions upstream of GXGXXG kinase motifs where TK fusion breakpoints are likely to occur followed by next generation sequencing and custom computational analysis. The feasibility of this approach (v1.0) was previously validated using cell line DNA (Chmielecki et al, 2010). We have since developed an improved version of our platform (v2.0) and used it to identify a novel c6orf204-PDGFRbeta fusion using DNA isolated from whole blood of a patient with T-cell acute lymphoblastic leukemia (T-ALL). The patient had an elevated white blood cell count with hypereosinophilia (HES) that was responsive to imatinib therapy. Multiple tumor samples (e.g. EGFR/KRAS/ALK wildtype lung adenocarcinomas, lung squamous cell carcinomas, ‘triple-negative’ breast carcinomas, and head and neck squamous cells carcinomas, etc.) are currently undergoing screening for other novel TK fusions, and candidate fusions are undergoing validation. This work was supported by an SU2C-AACR Innovative Research Grant to WP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-236. doi:10.1158/1538-7445.AM2011-LB-236
Potassium Deficiency and Vacuolar Myopathy
Authors: R. L. Westerman
Journal: JAMA (1971)

ABSTRACT To the Editor.— Oh et al (216:1858, 1971), have again called attention to vacuolar myopathy as one of the rare but dramatic and potentially fatal complications of  deficiency. The liberty I have taken in substituting the words potassium deficiency for hypokalemia is intentional. There are distinct differences between the two. Where possible, a differentiation should be made.Oh et al leave us with the impression that chlorthalidone was the primary cause of the patient's problem. However, they are careful to point out that she was a frequent laxative user and that laxative abuse is one of the well-known causes of hypokalemia. The striking thing about this case is the appearance of symptoms within seven weeks of instituting a (modest) diuretic program. In my experience, seven weeks is much too early for diuretics alone to produce such a severe example of  deficiency. In metabolic balance studies we found
PD3-2-3: Randomized phase I pharmacokinetic study of two doses of Erlotinib after failure of prior chemotherapy in patients with advanced NSCLC who continue to smoke
Authors: Penella J. Woll, William J. Petty, Mary O'Brien, Elaine Rankin, David Dunlop, Andrew Hughes, Marianne Nicolson, Jonathan Chick, Ramesh Boinpally, Allan Price
Journal: Journal of Thoracic Oncology (2007)
Breast‐feeding and atopic eczema dermatitis syndrome: protective or harmful?
Authors: P. A. Eigenmann
Journal: Allergy (2004)

Numerous studies have addressed the potential of breast‐feeding to protect for the development of allergic diseases, and in particular of atopic eczema dermatitis syndrome (AEDS). Although the majority of studies, as well as several meta‐analyses, are strongly in favour of breast‐feeding, there are some conflicting results and open issues. Furthermore, breast‐feeding might be detrimental in a subgroup of young infants with severe early manifestations of AEDS and immunoglobulin E sensitizations to common foods. The aim of this review is not to analyse systematically the current literature, but to suggest a scientifically and clinically based analysis of the benefits of breast‐feeding in atopic infants.
Improvement in mitral flow dynamics during exercise after percutaneous transvenous mitral commissurotomy. Noninvasive evaluation using continuous wave Doppler technique.
Authors: J Tamai, S Nagata, M Akaike, F Ishikura, K Kimura, M Takamiya, K Miyatake, Y Nimura
Journal: Circulation (1990)

Evaluation of mitral flow dynamics during exercise is critically important in patients who receive percutaneous transvenous mitral commissurotomy (PTMC) because limited mitral flow during exercise provokes hemodynamic deterioration and involves cardiogenic symptoms in patients with mitral stenosis. To examine mitral flow dynamics during exercise, we applied continuous wave Doppler technique in 20 patients with mitral stenosis. Exercise Doppler study was performed 2 days before and 5 days after PTMC. PTMC increased mitral valve area from 1.0 +/- 0.3 (mean +/- SD) to 1.9 +/- 0.5 cm2 and decreased mean transmitral pressure gradient from 8 +/- 2 to 4 +/- 1 mm Hg at rest. Moreover, PTMC decreased mean transmitral pressure gradient from 21 +/- 6 to 11 +/- 4 mm Hg at submaximal exercise. The extent of an increase in mitral valve area by PTMC correlated with a decrease in the mean transmitral pressure gradient at the submaximal exercise (r = -0.76, p less than 0.01) and that at rest (r = -0.52, p less than 0.05). Heart rate after PTMC during exercise was significantly lower than that before PTMC, indicating that the compensatory mechanism (tachycardia) to increase cardiac output during exercise is less necessary after PTMC. Thus, we conclude that the mitral flow dynamics during exercise is improved, as well as the resting mitral flow dynamics 5 days after PTMC, and that exercise Doppler study enabled us to make a noninvasive evaluation of the mitral flow dynamics in patients who receive PTMC.
Significance of chronic bifascicular block without apparent organic heart disease.
Authors: R C Dhingra, C Wyndham, R Bauernfeind, P Denes, D Wu, S Swiryn, K M Rosen
Journal: Circulation (1979)

Eighty-six of 452 patients (19%) with chronic bifascicular block were found to have no clinically apparent associated organic heart disease (OHD) and were defined as having primary conduction disease (PCD). Comparison of patients with PCD and OHD revealed a significantly lower incidence of the following clinical variables in the PCD patients (p less than 0.001): exertional angina, dyspnea, congestive heart failure, cardiomegaly, functional class I (all by study design), left bundle branch block and premature ventricular contractions. Both mean AH and HV intervals were significantly shorter in patients with PCD (p less than 0.01). The incidence of HV prolongation was 21% in PCD and 41% in OHD patients (p less than 0.001). All patients were prospectively followed for 21-2998 days with a mean +/- SEM of 1209 +/- 66 days for PCD and 1172 +/- 36 days for OHD. Atrioventricular (AV) block developed in three patients from the PCD group and 26 from the OHD group (NS), with spontaneous block occurring in one (1%) PCD patient and 19 (5%) OHD patients (p less than 0.05). Annual mortality due to sudden death as well as total cardiovascular mortality (including sudden death) for the 5-year follow-up was significantly lower in patients with PCD. Patients with PCD have significantly lower incidence of electrophysiologic abnormalities and subsequent spontaneous AV block as well as cardiovascular and sudden death mortality. The diagnosis of PCD based on clinical criteria probably underestimates the presence of underlying OHD, as suggested by a small but definite risk of cardiovascular mortality.
Marriage à la mode
Authors: George Dunea
Journal: BMJ (2006)

As a preamble to some notes on modern marriage, I should mention that in America the general practitioner has gone the way of the buffalo, having been replaced by family practice and primary care physicians. The latter is commonly referred to as the PCP, an abbreviation that brings to mind a chemical that might be poisoning our rivers and lakes. He or she could be a specialist, such as a cardiologist, but also functions as the patient's first point of …
AIDS associated with blood transfusion and haemophilia in Europe
Authors: F. Hamers
Journal: BMJ (1996)

EDITOR,—S Franceschi and colleagues report the incidence of AIDS associated with blood transfusion and haemophilia in Europe and the United States.1 However, they provide little information to help us understand these epidemics and erroneously suggest that the higher incidence in France than in other western European countries could be attributed to a delay in screening blood donations for HIV.

Rates of AIDS associated with blood transfusion and haemophilia depend on the use of blood and blood products, the general prevalence of HIV infection, and measures to ensure the safety of blood and blood products. These factors have differentially influenced the patterns of the two epidemics, which differ among and within countries (fig 1). …
Treatment of Rheumatoid Arthritis
Authors: Sanford H. Roth
Journal: JAMA (1982)

To the Editor.—   unfortunate choice of the title The Safety of Treating Rheumatoid Arthritis With Aspirin in the editorial by Eric P. Gall, MD, published inThe Journal(1982;247:63) no doubt contributed to confused, wide media coverage, which interpreted aspirin in a high-dosage regimen as a safe drug of first choice in treating most patients with rheumatoid arthritis. While this bias may at one time, indeed, have been acceptable, it is now subject to serious challenge, as almost 100 new alternative nonsteroidal anti-inflammatory and nonacetylated salicylate agents are compared with aspirin. None are necessarily superior in anti-inflammatory effect to aspirin when aspirin is taken appropriately at high-dose anti-inflammatory levels. All are consistently less toxic to the upper gastrointestinal (GI) tract, however. 1   Acid peptic complications are the most common and troublesome problems of anti-inflammatory therapy. I have recently reported on 137 patients with rheumatoid arthritis and osteoarthritis who had
Sulphaguanidine in Neonatal Gastro-enteritis
Authors: J. L. Henderson
Journal: BMJ (1943)

<h3>Background</h3> It is unknown whether lesions in human TB are hypoxic or whether this influences disease pathology. Human TB is characterised by extensive lung destruction driven by host matrix metalloproteinases (MMPs), particularly collagenases such as matrix metalloproteinase-1 (MMP-1). <h3>Methods</h3> We investigated tissue hypoxia in five patients with PET imaging using the tracer [<sup>18</sup>F]-fluoromisonidazole ([<sup>18</sup>F]FMISO) and by immunohistochemistry. We studied the regulation of MMP secretion in primary human cell culture model systems in normoxia, hypoxia, chemical hypoxia and by small interfering RNA (siRNA) inhibition. <h3>Results</h3> [<sup>18</sup>F]FMISO accumulated in regions of TB consolidation and around pulmonary cavities, demonstrating for the first time severe tissue hypoxia in man. Patlak analysis of dynamic PET data showed heterogeneous levels of hypoxia within and between patients. In <i>Mycobacterium tuberculosis</i> (<i>M.tb)</i>-infected human macrophages, hypoxia (1% pO<sub>2</sub>) upregulated MMP-1 gene expression 170-fold, driving secretion and caseinolytic activity. Dimethyloxalyl glycine (DMOG), a small molecule inhibitor which stabilises the transcription factor hypoxia-inducible factor (HIF)-1α, similarly upregulated MMP-1. Hypoxia did not affect mycobacterial replication. Hypoxia increased MMP-1 expression in primary respiratory epithelial cells via intercellular networks regulated by TB. HIF-1α and NF-κB regulated increased MMP-1 activity in hypoxia. Furthermore, <i>M.tb</i> infection drove HIF-1α accumulation even in normoxia. In human TB lung biopsies, epithelioid macrophages and multinucleate giant cells express HIF-1α. HIF-1α blockade, including by targeted siRNA, inhibited TB-driven MMP-1 gene expression and secretion. <h3>Conclusions</h3> Human TB lesions are severely hypoxic and <i>M.tb</i> drives HIF-1α accumulation, synergistically increasing collagenase activity which will lead to lung destruction and cavitation.
Reduction of pulmonary capillary blood volume in patients with severe unexplained pulmonary hypertension.
Authors: C. Borland, Y. Cox, T. Higenbottam
Journal: Thorax (1996)

BACKGROUND: Unexplained or primary pulmonary hypertension results in an obliteration and obstruction of resistance pulmonary arteries. In these patients gas exchange is impaired and the measurement of gas transfer for carbon monoxide is usually reduced. This has been thought to represent a reduction in pulmonary alveolar capillary blood volume (Vc). A single breath test, measuring simultaneously the uptake of both nitric oxide (NO) and carbon monoxide (CO), provides a simple and practical measurement of membrane diffusion (Dm) and Vc. METHODS: A standard single breath test for the measurement of gas transfer for carbon monoxide (TLCO) was adapted to include NO (40 ppm) in the inhaled gas mixture and a breath-hold time at total lung capacity of 7.5 seconds was used. Twelve patients with primary pulmonary hypertension and 10 similar normal volunteers were studied while seated at rest. RESULTS: The patients had reduced values for TLCO and TLNO. The mean (SD) value of Dm in the patients was 36.7 (32.1) mmol/min.kPa compared with 52.8 (23.9) mmol/min.kPa in the normal subjects. Vc in the patients was 0.03 (0.03) 1 and 0.06 (0.01) 1 in the normal subjects. CONCLUSIONS: The simultaneous measurement of NO and CO uptake is possible in healthy volunteers and patients with primary hypertension. In these patients capillary blood volume is reduced compared with normal subjects.
Immunogold staining of microtubules in resting and activated platelets
Authors: Gines Escolar, John Sauk, Maria Luisa Bravo, Marlys Krumwiede, James G. White
Journal: American Journal of Hematology (1987)

Abstract A circumferential microtubule is known to support the discoid form of resting platelets, but its fate following exposure of the cells to aggregating agents is uncertain. The present study has employed an immunocytochemical approach to follow the fate of the circumferential microtubule in activated platelets. Monoclonal antibodies to tubulin and to vinculin and a polyclonal antibody to actin were incubated with isolated microtubule coils and stained with staphylococcal protein A coupled to immunogold in order to test their specificity. Thin sections of glycolmethacrylate embedded platelets before and after exposure to thrombin for 15, 30 and 60 s were stained with antibodies to tubulin and actin. Immunogold particles showed a high specificity for isolated MT coils stained for tubulin, modest intensity for actin, and none for vinculin. Gold particles were randomly distributed in thin sections of resting and activated platelets stained for actin. Immunogold was limited to the circumferential microtubule in resting platelets and constricted coils in thrombin‐activated cells. The number of gold particles in areas of cytoplasm away from microtubules in platelets stained with antitubulin antibody increased slightly following thrombin activation, but the change was not significant. Results support the concept that microtubule coils supporting the discoid form of resting platelets do not dissolve following exposure of the cells to potent agonists.
Lymphoblastic transformation of chronic myelomonocytic leukemia in an infant
Authors: Masuji Yamamoto, Makiko Nakagawa, Noriko Ichimura, Fumiko Ohtsuki, Yoshitoshi Ohtsuka, Yoshiaki Tsujino, Aiichiro Tanaka, Takashi Kamiya, Hiroyoshi Wada
Journal: American Journal of Hematology (1996)

A 10-month-old infant with chronic myelomonocytic leukemia (CMML) of 5 months' duration, who had been treated only with transfusion, displayed leukemic transformation characterized by lymphoid morphology, PAS positivity, and myeloperoxidase negativity. Surface marker analysis of blast cells revealed expression of lymphoid-associated antigens (CD10 and CD19) but not myeloid-associated antigens (CD13, CD14, and CD33). These findings suggest that some cases of infantile CMML are clonal disorders arising in a pluripotent stem cell that can also differentiate along the lymphoid cell lineage. © 1996 Wiley-Liss, Inc.
Dysplasia and aneuploidy as markers of malignant degeneration in Barrett's oesophagus. The Rotterdam Oesophageal Tumour Study Group.
Authors: M B Menke-Pluymers, A H Mulder, W C Hop, M van Blankenstein, H W Tilanus
Journal: Gut (1994)

The role of dysplasia and aneuploidy as markers in columnar epithelium for malignant degeneration in Barrett9s oesophagus was compared in a case control study comprising 38 patients with benign Barrett9s oesophagus and 50 patients with Barrett9s oesophagus associated with adenocarcinoma. Tissue specimens of columnar epithelium were reviewed for the presence of specialised columnar epithelium and the grade of dysplasia. Ploidy was determined using the method for formalin fixed paraffin wax embedded tissue described by Hedley. There was no significant difference in the frequency of specialised columnar epithelium between both groups. Dysplasia was found more often in columnar epithelium associated with adenocarcinoma compared with benign Barrett9s oesophagus (p &lt; 0.001). Multivariate analysis using logistic regression showed an increased risk of malignancy in Barrett9s oesophagus in case of dysplasia (odds ratio 9.4, p = 0.003 for mild dysplasia and 33.1, p &lt; 0.001 for moderate or severe dysplasia). Ploidy was not statistically significantly correlated with dysplasia. Aneuploidy or increased G2/tetraploidy proved to be an independent risk factor for younger patients (age &lt; 65 years: odds ratio 44.7, p = 0.003). In conclusion, dysplasia and aneuploidy or increased G2/tetraploidy in columnar epithelium are independent risk factors for malignant degeneration. Patients with these risk factors should be offered a more intensive screening programme.
Burkitt's lymphoma presenting as ophthalmoplegia in an elderly male
Authors: Shervl A. Russ, Omar H. Yumen
Journal: American Journal of Hematology (1994)

CAWCAR 13 (35%) 6 (16%) CAWBenin 19(51%) 23 (64%) BeniMBenin 4(11%.)7 (20%) Others 1(3%) -Blood samples for hematological and DNA analysis were obtained from 73 nonrelated patients with homozygous sickle cell anemia (from the University Hospital of UNICAMP, Campinas, State of Sio Paulo, and from the University Hospital of Federal University of Bahia and of Oncology and Hematology Center "Eric Loffler," Salvador.State of Bahia).The diagnosis was based on clinical and laboratory findings [2].High molecular weight DNA was isolated from peripheral blood leukocytes with proteinase K or urea using standard procedures [2].The haplotype determination was carried out by PCR amplification of the region of the polimorfic site followed by digestion with appropriate enzyme.The following restriction sites were analysed: Xmn I of the position -158 of the G-y gene, Hind 111 in IVS2 of *Y.Hind I11 of IVS2 of 'y.Hinc I1 in the $p, Hinc 11 at 3' of JIp and Hinf I at 5' of p.The primers and conditions utilized
ABC of antithrombotic therapy: Antithrombotic therapy for atrial fibrillation
Authors: G. Y H Lip
Journal: BMJ (2002)

<h3>Objectives</h3> Evaluate the effect of chemotherapy treatment on PAR glycohydrolase (PARG), other member of poly(ADP-ribose) metabolism, in high-grade serous ovarian cancer patients (HGSOC). <h3>Methods</h3> Two HGSOC cohorts were evaluated by immunohistochemistry: 54 chemo-naïve HGSOC patients (45 HGSOC, 9 borderline, 4 normal tissue) and 53 HGSOC chemo-treated patients (44 HGSOC, 9 borderline, 7 normal tissue). In addition, we used <i>in silico</i> analysis to evaluate the effect of PARG mRNA expression in ovarian cancer and its relation with patient outcome. <h3>Results</h3> Our results showed that chemo-naïve patients have significant higher levels of PARG expression compared to borderline and normal (62.2%, 44.4% and 0% respectively). Interestingly, these levels were reduced in HGSOC patient samples that have received chemotherapy (45.44%, 44%, 0%, respectively, p&lt;0.03). Indeed, this demonstrated that chemotherapy induces a reduction in PARG expression to levels equal to the borderline tumors. Furthermore, we found a dramatic re-localization of PARG protein to the cytoplasm in chemo-treated patients (100%) compared with chemo-naïve HGSOC samples that were localized in the nucleus (80%,P&lt;0.05).<i>In silico</i> analysis of 1500 ovarian cancer patients revealed that PARG is up-regulated in ovarian cancer in comparison with normal tissue and highly express in advance-metastatic HGSOC. Moreover, its expression in advance disease was associated with shorter overall survival. <h3>Conclusions</h3> Our results showed that chemotherapy decreased PARG expression and re-localized it into the cytoplasm. Moreover, our findings highlights the possible use of PARG inhibitors as an adjuvant therapy to treat recurrent ovarian cancer together with chemotherapy and other new-targeted drugs such as PARP inhibitors.
False Aneurysm After Carotid Endarterectomy
Authors: Lucian C. Buscaglia
Journal: JAMA (1969)

<h3>To the Editor:—</h3> A case of false aneurysm of the carotid artery secondary to dehiscence of silk sutures holding a Dacron patch is presented. Symptoms of cerebral dysfunction secondary to probable embolization from the false aneurysm have focused our attention on this diagnosis as a possible cause of recurrent symptoms in patients who have previously had carotid artery surgery. False aneurysms have been reported after vascular reconstruction to the lower extremities.<sup>1</sup>To the best of our knowledge, false aneurysms after carotid artery reconstruction have not been previously described. This presentation reports a symptomatic false aneurysm of the carotid artery which occurred six years after carotid endarterectomy. <h3>Report of a Case:—</h3> A 56-year-old man was admitted to the San Francisco Veterans Administration Hospital on April 10, 1968, with acute hemiparesis on the right side and dysarthria. Several months prior to admission the patient had had an episode of transient right