tbuckley/cabot-search huggingface dataset:
Diagnostic Accuracy of 64-Slice Computed Tomography Coronary Angiography
Authors: W. Bob Meijboom, Matthijs F.L. Meijs, Joanne D. Schuijf, Maarten J. Cramer, Nico R. Mollet, Carlos A.G. van Mieghem, Koen Nieman, Jacob M. van Werkhoven, Gabija Pundziute, Annick C. Weustink, Alexander M. de Vos, Francesca Pugliese, Benno Rensing, J. Wouter Jukema, Jeroen J. Bax, Mathias Prokop, Pieter A. Doevendans, Myriam G.M. Hunink, Gabriel P. Krestin, Pim J. de Feyter
Journal: Journal of the American College of Cardiology (2008)
Dare We Go Gently
Authors: C Feudtner
Journal: JAMA (2000)

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Abstract 5057: CXCR4 Antagonist AMD3100 Preserves Cardiac Function After Myocardial Infarction (MI) via CXCR4 Dependent and Independent Pathways
Authors: Kentaro Jujo, Hiromichi Hamada, Haruki Seguchi, Tina Thorne, Ekaterina Klyachko, Marie-Ange Renault, Douglas W Losordo
Journal: Circulation (2009)

Background: Recent studies have been shown that CXCR4 antagonist AMD3100 rapidly mobilizes stem/progenitor cells from BM and prior studies suggested a potential therapeutic effect in MI. This study was performed to explore the mechanisms of this effect in a mouse ischemia reperfusion (IR) injury model. Methods and Results: 8- to 12-week-old wild-type (WT) mice were treated with single sc injections of either AMD3100 (5 mg/kg) or saline immediately after IR injury (60 min-LAD occlusion followed by reperfusion). FACS analyses identified a significant increase in the number of circulating EPCs(culture method; Day7: 76.0±23.9 vs 34.6±6.1 cells/uL PB, p &lt;0.05) in AMD-treated mice on days 3–7 after IR, and ELISA indicated that AMD increased levels of MMP-9 and soluble Kit ligand in BM(Day 3 MMP-9: 88.6±12.7 vs 53.9±24.5 ug/mL, p &lt;0.05; sKitL: 20.4±3.3 vs 13.0±4.1 vs. pg/mL, p &lt;0.05). On day 3 after IR histo analyses revealed a lower ratio of infarct area/area at risk (AAR) (15.8±2.2% vs 31.9±9.4, p &lt;0.05) in AMD-treated mice. On day 28 AMD-treated mice had greater capillary density in AAR (188.7±52.5 vs 113.5±13.4/HPF, p &lt;0.05) and less fibrosis(27.6±10.9 vs 43.3±17.0%, p &lt;0.05). 4 wks after IR, echocardiograpy showed better LV function in AMD-treated mice (Day28 LVFS: 38.3±6.1% vs. 28.0±5.0, p &lt;0.05). To determine whether favorable effect of AMD on recovery after IR is dependent on CXCR4 expression on BM cells, we induced IR injury in WT mice transplanted with BM from CXCR4 conditional KO donor mice. In BM-transplanted mice, AMD continued to increase EPC mobilization from BM after IR, as well as increasing levels of MMP-9 and sKit ligand in BM(all p&lt;.05). However, the enhanced cardiac functional recovery observed in mice with WT BM was lost in mice with CXCR4 null BM . These results indicate that the EPC mobilizing effect of AMD is CXCR4 independent, while the BM CXCR4 is essential for AMD mediated preservation of cardiac function after IR. Conclusions: This study provides novel mechanistic insights into the cardioprotective effects of CXCR4 antagonist AMD3100 indicating that MMP-9 and Kit ligand contribute to AMD-induced EPC mobilization independent of CXCR4 but that the receptor is essential for AMD mediated myocardial protection.
Abstract 3940: Identification of Novel Genetic Variants within the LPA Gene that are Associated with Serum Lp(a) Levels and Myocardial Infarction
Authors: Katharina J Neureuther, Klaus Stark, Andrea Baessler, Silke Wiedmann, Angela Doering, Stephan R Holmer, Guenter A Riegger, Christian Hengstenberg, Marcus Fischer
Journal: Circulation (2006)

Background : Serum Lp(a) levels of the atherogenic Lipoprotein (a) [Lp(a)] are under the genetic control of the Apo(a) locus. In Caucasians several polymorphisms of the  LPA  gene have been shown to influence the size and amount of apo (a): 50 % of the Lp(a) level are determined by the number of kringle IV type 2 repeats (KIV-2), with a low number of repeats causing higher levels. Another 45% of the genetic variation of Lp(a) levels can be explained with polymorphisms in the promoter region (i.e. the pentanucleotidrepeat (PNR) polymorphism) of the gene and other, yet unidentified variations in the  LPA  gene. Thus, we associated additional polymorphisms within the  LPA  gene with Lp(a) levels and MI.   Methods : Four SNPs within the  LPA  gene were explored in addition to the formerly investigated KIV and PNR polymorphisms. The TaqMan technology was used for genotyping of subjects in whom Lp(a) levels were available: 975 individuals of the general population (echocardiographic substudy of the third MONICA survey Augsburg), as well as 595 MI patients and 586 sibs affected from CAD from the Regensburg MI sib-pair registry. Moreover, n=450 samples from the KORA MI registry were used to verify the results.   Results : Three of the four SNPs were in linkage disequilibrium with each other but not with the KIV-2 and PNR polymorphisms. Particularly one SNP (Intron 34) was strongly associated with Lp(a) levels across all populations, in both men and women (MONICA: CC genotype: 50±11, CT: 30±2, TT: 21±1 mg/dl (±SEM), p=0,0019; MI patients: CC: 66±16, CT: 51±3, TT: 32±2 mg/dl, p   Conclusion : We identified novel genetic variants within the  LPA  gene, that are associated with Lp(a) serum levels and a higher risk of MI in independent populations. These effects seem to be somewhat independent from the size of apo(a) isoforms, and may thus contribute significantly to the variability of Lp(a) levels and its risk of coronary syndrome.
Pneumocystis carinii (jíroveci) pneumonia (PCP) in ICU patientswith hematological malignancies
Authors: Jana Skřičková, Jiří Mayer, Jiří Vorlíček, Vladimír Znojil, Zdeněk Merta
Journal: European Respiratory Journal (2004)

Over 7 years, 179 HIV-negative patients were examined with
suspicion on PCP. Of them, 120 (67%) were ICU patients with
hematological malignancies. PCP was established in 39 (32.5%)of
120 patients so-called typical X-ray picture was not invariably
found. Complete or partial improvement occurred in 30 (76.9%)
patients.
Iris Heterochromia and Unilateral Eyelash Hypertrichosis
Authors: Rajesh C. Rao, Tiffany N. S. Ballard, Teresa C. Chen
Journal: JAMA (2015)

An 87-year-old female with a history of open-angle glaucoma presented with longer, thicker eyelashes on the right side compared to the left. Her irides were also different colors, as the right iris was brown and the left was hazel (green-brown). The patient had noticed a gradual darkening of her right iris and lengthening of her eyelashes over the last year, but denied visual changes or foreign-body sensation. Past medical history included a remote history of breast cancer treated by lumpectomy and radiation therapy, cerebrovascular accident, hypercholesterolemia, and hypertension. Her medications included bimatoprost, atenolol, atorvastatin, and clopidogrel.
346. Characterization of Adeno-Associated Virus Sequences in Human Tissues
Authors: Chun-Liang Chen, Ryan L. Jensen, Bruce C. Schnepp, K. Reed Clark, Philip R. Johnson
Journal: Molecular Therapy (2004)

Top of pageAbstract
Background. Infection with wild-type adeno-associated virus (AAV) is common in humans. However, the biology and molecular epidemiology of AAV infection is poorly understood. Because vectors based on AAV are now being used in human gene transfer trials, a more complete characterization of wild-type AAV infection is needed. To that end, we have surveyed fresh (tonsils) and archived frozen human tissues for the presence of AAV DNA.

Methods. Total genomic DNA was isolated from 175 tissue samples: tonsil (n = 101), spleen (n = 21), liver (n = 19), lung (n = 16), muscle (n = 15), and heart (n = 3). Samples were screened by degenerate PCR for the presence of AAV and human adenovirus sequences. AAV sequences were further amplified and cloned for sequence analyses.

Results. AAV DNA was detected in 7 of 101 (7%) tonsil samples and 2 of 74 other tissues (1 spleen and 1 lung). Adenovirus sequences were identified in 19 of 101 (19%) tonsils, but not in any other tissues. Two tonsil samples contained both AAV and adenovirus sequences. The amount of AAV DNA in each of the positive tissues was determined by quantitative PCR; levels ranged between 76 – 15,500 AAV copies/microgram of total DNA. Complete capsid sequences were generated from all 9 AAV containing tissues. Sequence analyses showed that 8 of the capsid sequences were AAV-2 like (96 – 98% amino acid identity), while the single spleen isolate was intermediate between genotypes 2 and 3 (91% vs AAV2, 92% vs AAV3). In this particular isolate, the majority of the amino acid substitutions mapped to surface exposed hypervariable domains.

Conclusions. Following natural infection, AAV DNA can be easily found in human tissues, especially at the presumed portal of entry (oropharynx). In our cohort, the most common genotype was AAV2. Interestingly, the AAV2 capsid sequences were not identical to the published AAV2 sequence. The finding of AAV DNA outside of the oropharynx suggests that wild-type AAV can and does disseminate during natural infection.
Predictors of Cardiac Rehabilitation Referral in Coronary Artery Disease Patients
Authors: Todd M. Brown, Adrian F. Hernandez, Vera Bittner, Christopher P. Cannon, Gray Ellrodt, Li Liang, Eric D. Peterson, Ileana L. Piña, Monika M. Safford, Gregg C. Fonarow
Journal: Journal of the American College of Cardiology (2009)
Abstract 2624: The novel Bruton's tyrosine kinase inhibitor ACP-196 shows <i>in vivo</i> efficacy against human chronic lymphocytic leukemia cells xenografted to the NSG mouse model
Authors: Carsten U. Niemann, Arnau Montraveta, Sarah E. M. Herman, Tim Ingallinera, Tjeerd Barf, Dolors Colomer, Adrian Wiestner
Journal: Cancer Research (2014)

Abstract Background: Targeting Bruton's tyrosine kinase (BTK), an essential kinase in the B cell receptor (BCR) pathway in patients with chronic lymphocytic leukemia (CLL) has proven very effective. For the first generation BTK inhibitor ibrutinib, clinical response rates &amp;gt;70% and 75% progression free survival &amp;gt;2 years have been reported for previously treated patients (Byrd, NEJM, 2013). ACP-196 is a novel, second generation, irreversible BTK inhibitor that may show advantages in terms of binding specificity and drug-drug interactions compared to the first generation BTK inhibitor. Survival and proliferation of CLL cells is highly dependent on microenvironment interaction, which must be taken into consideration when testing new drugs for CLL. We have previously shown that human CLL cells engrafted in the spleen of NSG mice have comparable tumor biology to human lymph node resident CLL cells (Herman, Leukemia, 2013). We here demonstrate the in vivo effects of ACP-196 monotherapy against CLL cells in the NSG xenograft model. Methods: Peripheral blood mononuclear cells from previously untreated CLL patients were injected intravenously into NSG mice. Mice received ACP-196 through the drinking water. The effect of ACP-196 on xenografted CLL cells from peripheral blood and spleen was assessed by flow cytometry. Results: At all dose levels tested, ACP-196 significantly inhibited proliferation of human CLL cells in the spleens of NSG mice, as measured by Ki67 expression (P=0.002). The mean Ki67 decrease was 58%, 70% and 73%, respectively for the low, intermediate, and high dose level compared with vehicle. Tumor burden in spleens from mice treated with the high dose of ACP-196 decreased compared with the vehicle treated group (P=0.007). As seen with other BCR inhibitors, ACP-196 transiently increased CLL cell counts in the peripheral blood in a dose dependent manner (p=0.01). ACP-196 inhibited BCR signaling in vivo, as demonstrated by reduced phosphorylation of PLCγ2. Conclusions: Results presented here for ACP-196 are in accordance with the expected profile of an irreversible BTK inhibitor. The NSG CLL xenograft model will be used for comparative testing of different BTK inhibitors and exploration of combination therapies. Citation Format: Carsten U. Niemann, Arnau Montraveta, Sarah E. M. Herman, Tim Ingallinera, Tjeerd Barf, Dolors Colomer, Adrian Wiestner. The novel Bruton's tyrosine kinase inhibitor ACP-196 shows in vivo efficacy against human chronic lymphocytic leukemia cells xenografted to the NSG mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2624. doi:10.1158/1538-7445.AM2014-2624
European Academy of Allergology and Clinical Immunology ‘EAACI’ guidelines for continuing medical education*
Authors: S. Buscaglia, A. G. Palma‐Carlos, G. W. Canonica
Journal: Allergy (1997)

Buscaglia S, Palma‐Carlos AG, Canonica GW. European Academy of Allergology and Clinical Immunology ‘EAACI’ guidelines for continuing medical education. Essentials for accreditation, standards for commercial support, and system of credits.
Bence-Jones Proteins and Light Chains of Immunoglobulins
Authors: Alan Solomon
Journal: New England Journal of Medicine (1976)

Role of the Light Chain in the Antibody-Combining SiteRecombination and affinity-labeling experiments have provided evidence that both heavy and light chains are required for antibody activity, a finding indicating that each chain contributes to the antigen-binding site.45 However, data derived from hapten-binding and viral neutralization studies indicate activity expressed individually by heavy chains and light chains, respectively,97 98 99 100 101 and suggest that this phenomenon depends, in part, on the fact that either chain can exist in the dimeric form.100 , 101 The postulation100 that each species in the dimer interacts in a manner analogous to the heavy-light chain interaction to form the antibody-combining . . .
Abstract 12595: Hybrid Surgical and Catheter Ablation of Atrial Fibrillation: Comparison of Techniques
Authors: Anil Gehi, John P Mounsey, Sruthi Cherkur, Andy Kiser
Journal: Circulation (2014)

Introduction: Hybrid catheter/surgical ablation (HyCASA) of AF may be more effective than endocardial (endo) ablation (abl) in pts with history of failed ablation or structural heart disease.

Hypothesis: There may be difference in the many approaches to HyCASA abl.

Methods: In 38 pts with long-standing pers (LSP) (3), pers (25), or parox (10) AF, trans-abdominal HyCASA was performed with epicardial (epi) unipolar RF (nContact VisiTrax, Morrisville, NC). Then in 29 pts with LSP (5), pers (22), or parox (2) AF right trans-thoracic HyCASA was performed with epi bipolar/unipolar RF (AtriCure Fusion, West Chester, OH). Epi isolation of pulmonary veins, posterior LA, and posterior RA was followed by endo abl including completion of epi lesion set, CFAE, and any residual flutter ablation. Any AF > 2 min found by continuous monitoring (ILR or PM/ICD in all pts) after a 3-mo blanking period was considered a recurrence.

Results: Age was 61.8 (9.6, mean+SD); 79% were male. Co-morbidities included HTN (75%), DM (29%), CAD (18%), HF (25%), and obesity (BMI>30) (69%). LA size was 4.9 (0.7) (range: 3.3-6.8) cm; EF was 51.9 (10.2) (range 15-70) %. AF duration was 6.4 (5.7) (range: 0.5-25) yrs. All had failed drug therapy and 46% had failed prior endo abl (1.5 abl/pt). Pts undergoing HyCASA using thoracic/AtriCure approach were more likely pers (93% vs 74%, p=.04). There was no other difference between groups. Hospital length of stay was longer (7.0 vs 3.7 days, p<.001) and there were more bleeding complications (3 vs 0, p=.04) in the thoracic/AtriCure approach. There was no peri-procedural mortality or stroke. At median follow-up of 294 days, success was 72% with the thoracic/AtriCure approach and 53% with the abdominal/nContact approach (p=.10) (Graph).

Conclusions: HyCASA AF ablation with the thoracic/AtriCure compared with the abdominal/nContact approach trends toward better efficacy but has an increased risk for complications and longer hospital length of stay.

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Zebrafish homolog of the leukemia gene CBFB: its expression during embryogenesis and its relationship to scland gata-1 in hematopoiesis
Authors: Trevor Blake, Neeraj Adya, Cheol-Hee Kim, Andrew C. Oates, Leonard Zon, Ajay Chitnis, Brant M. Weinstein, P. Paul Liu
Journal: Blood (2000)
UNSUSPECTED PHEOCHROMOCYTOMA RESULTING IN POSTOPERATIVE DEATH
Authors: B Z PAULSHOCK, E R MILLER
Journal: Annals of Internal Medicine (1956)

Case Reports1 March 1956UNSUSPECTED PHEOCHROMOCYTOMA RESULTING IN POSTOPERATIVE DEATHBERNADINE Z. PAULSHOCK, M.D., EDGAR R. MILLER, M.D., F.A.C.P.BERNADINE Z. PAULSHOCK, M.D.Search for more papers by this author, EDGAR R. MILLER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-44-3-573 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBecause of prolonged life span an increasing number of elderly patients with hypertension is being subjected to various types of surgical procedures. It is therefore important to remember that lethal hypertensive crises from unsuspected pheochromocytomas may be precipitated by the trauma of anesthesia and surgery.In a recent review of the literature by Apgar and Papper,1it was disclosed that the operative mortality in patients on whom surgery was performed without prior knowledge of the presence of pheochromocytoma was 50%. Fifteen of the 16 patients who died did so within two to 48 hours postoperatively, in irreversible circulatory collapse. A...Bibliography1. ApgarPapper VEM: Pheochromocytoma; anesthetic management during surgical treatment, Arch. Surg. 62: 634, 1951. CrossrefGoogle Scholar2. GoldenbergAranowSmithFaber MHAM: Pheochromocytoma and essential hypertensive vascular disease, Arch. Int. Med. 86: 823, 1950. CrossrefGoogle Scholar3. Editorial: The diagnosis of pheochromocytoma, Ann. Int. Med. 39: 1333, 1953. LinkGoogle Scholar4. Green DM: Pheochromocytoma and chronic hypertension, J. A. M. A. 131: 1260, 1946. CrossrefMedlineGoogle Scholar5. WellsBowman AHPG: The clinical and pathological identity of pheochromocytoma, J. A. M. A. 109: 1176, 1937. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Wilmington, Delaware*Received for publication December 31, 1954.From the Department of Medicine, The Delaware Hospital, Inc., Wilmington, Delaware. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBibliographyDas PhäochromocytomPheochromocytoma in the adult and in the childPHEOCHROMOCYTOMA AND PREGNANCY*IRVING L. STUTZ, M.D., F.A.C.P., SIDNEY A. ROSENBURG, M.D., HAROLD M. COHEN, M.D., ROBERT CHAMOVITZ, M.D., IRWIN BOGARAD, M.D.Pheochromocytoma: A review of the literature 1 March 1956Volume 44, Issue 3Page: 573-575KeywordsAnesthesiaEdemaElderlyHospital medicineHypertensionMortalityPheochromocytomaSurgeryTrauma surgery Issue Published: 1 March 1956 PDF DownloadLoading ...
Abstract 20439: Novel Long Intergenic Noncoding RNAs Modulate Adipose Functions in Human
Authors: Xuan Zhang, Rachel Ballantyne, Chenyi Xue, Jane F Ferguson, Brian Gregory, Mingyao Li, Muredach P Reilly
Journal: Circulation (2014)

Recently long intergenic noncoding RNAs (lincRNAs) have emerged as key mediators of cellular differentiation and functions in a variety of cell systems critical to cardiovascular and metabolic disorders. To identify and investigate novel functional lincRNAs in human adipose, we performed deep high-throughput RNAseq (&gt;200 million reads/sample) in subcutaneous adiposes of 13 health volunteers. Of an integrated dataset of 54,944 human lincRNAs, 6,558 lincRNAs were detected. Here we report 2 cytoplasmic adipose lincRNAs, linc-DMRT2 and linc-NFE2L3-1, were detected in human adipocytes but not monocytes or macrophages. Linc-DMRT2, one of the most abundant adipose lincRNAs, was markedly induced during in vitro human adipocyte differentiation. Notably, single molecule RNA FISH (fluorescence in situ hybridization) demonstrated that linc-DMRT2 were exclusively present in adipocyte cytoplasma and co-localized with processing bodies (P-bodies) marker, GW182, suggesting its potential role in modulating turnover of certain RNA species. In addition, linc-NFE2L3-1, predominantly detected in adipose and skeleton muscle, is localized near an established GWAS locus associated with waist-hip ratio adjusted BMI. We identified 4 SNPs in linc-NFE2L3-1 reaching genome wide significance for BMI (lead SNP rs10267498, P=2.73х10 -8 ). Linkage disequilibrium analysis confirmed linc-NFE2L3-1 harbors stronger GWAS signals than protein-coding genes in the locus, suggesting lincRNA might be causal for GWAS association with BMI. Bioinformatic prediction algorithms identified potential binding sites in linc-DMRT2 and linc-NFE2L3-1 for multiple microRNAs that have been demonstrated to regulate adipogenesis (e.g. miR-15 a/b and let-7) or adipocyte functions (e.g. miR-320). In summary, our data suggest that cytoplasmic linc-DMRT2 and linc-NFE2L3-1 may play important roles in adipocyte biology by functioning as competing endogenous RNAs and binding specific microRNAs that mediate adipocyte cellular functions. Genetic variation in such human linRNAs may contribute to cardiometabolic traits.
One hundred years ago: A Victorian polymath
Authors: M C Petch
Journal: BMJ (1998)

On 19 March 1898 the BMJ published a report from Dr C B Plowright, entitled “On the epidemic of enteric fever at King's Lynn, October 1897” ( BMJ 1898;i:770-2). The whole epidemic “comprised well on for 500 cases” of which 50 were analysed and formed the basis of the report. The author was the local medical officer of health; it seemed obvious to him that the onset of the epidemic was triggered by a heavy rain storm on 29 September when 2.25 inches fell in 24 hours. This permitted an examination of the incubation period because 19 of the 50 cases were notified during the last week in October. Only one patient died but the morbidity was considerable and the average time spent in bed was six weeks. Convalescence was reported to be “very slow; many …