tbuckley/cabot-search huggingface dataset:
Influence of β-Blockade on Ejection Fraction, ANP, and cGMP in Patients After Myocardial Infarction
Authors: Susanne Hauptlorenz
Journal: JAMA (1989)

To the Editor. —  Atrial natriuretic peptide (ANP) is a peptide concerned with the homeostasis of blood volume produced by cardiomyocytes. Atrial stretch, for example in arrhythmias 1 and congestive heart failure, 2 leads to a release of ANP into the plasma followed by an intracellular and intravascular increase of cyclic 3′,5′—guanosine monophosphate (cGMP), its second messenger. 3 The question arises whether ANP and cGMP are useful tools to quantify slight congestive heart failure or to control medical therapy. We therefore investigated the ejection fraction and ergometric workload and compared these with the biochemical markers ANP and cGMP. In addition, we studied the influence of β-blockade on these factors.  Study.—  Nine patients who had a myocardial infarction 6 to 8 months previously gave informed consent and entered the study. All patients went through two cycles of 2 weeks' length. The first was a control period, in which all medication except
Abstract A80: Somatic cancer mutations in human mtDNA show neutral and positive selection
Authors: Peter Stafford, Estella B. Chen-Quin
Journal: Cancer Research (2009)

Abstract The majority of cancers exhibit somatic mutations in the mitochondrial chromosome (mtDNA). Whether these mutations play a causal role or are merely an effect is an issue of on-going uncertainty. To study the role of somatic mtDNA mutations in cancer, we present a meta-analysis of 356 tumor sequences of multiple cancer types from the literature. As tumor formation is a type of somatic evolution, we examine the mutation pattern for whether the cancer DNA variation is consistent with drift (random forces) or selection. We also compare the cancer mutation pattern to that observed at the organismal or population level in order to gain insight on the mutation process in cancer cells. Among germline sequences, all mtDNA genes show a strong deficiency of amino acid changes, reflecting negative selection during human history and consistent with functional constraints at the organismal level. In somatic cancer sequences, mtDNA genes show either relaxed negative selection relative to germline or a mutation pattern consistent with neutrality. ND3, CO3, and ND4L in particular show cancer missense mutation rates nine - 18 times that of their counterpart genes at the germline level. Bootstrap analysis of the cancer-specific missense mutations show Cytochrome B and ND6 to have changes occurring in positions of unusually high conservation, suggesting that tumors select for mutations in residues of high functionality. These results support relaxed negative selection or neutrality for somatic mtDNA mutations in cancer, with the later potential for positive selection of alterations that impair mitochondrial function. Citation Information: Cancer Res 2009;69(23 Suppl):A80.
The stem cell niche of human livers: Symmetry between development and regeneration
Authors: Lili Zhang, Neil Theise, Michael Chua, Lola M. Reid
Journal: Hepatology (2008)

Abstract Human livers contain two pluripotent progenitors: hepatic stem cells and hepatoblasts. The hepatic stem cells uniquely express the combination of epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), cytokeratin (CK) 19, albumin ±, and are negative for α-fetoprotein (AFP). They are precursors to hepatoblasts, which differ from hepatic stem cells in size, morphology, and in expressing the combination of EpCAM, intercellular cell adhesion molecule (ICAM-1), CK19, albumin++, and AFP++. The hepatic stem cells are located in vivo in stem cell niches: the ductal plates in fetal and neonatal livers and canals of Hering in pediatric and adult livers. The hepatoblasts are contiguous to the niches, decline in numbers with age, wax and wane in numbers with injury responses, and are proposed to be the liver's transit-amplifying cells. In adult livers, intermediates between hepatic stem cells and hepatoblasts and between hepatoblasts and adult parenchyma are observed. Amplification of one or both pluripotent cell subpopulations can occur in diseases; for example, hepatic stem cell amplification occurs in mild forms of liver failure, and hepatoblast amplification occurs in forms of cirrhosis. Liver is, therefore, similar to other tissues in that regenerative processes in postnatal tissues parallel those occurring in development and involve populations of stem cells and progenitor cells that can be identified by anatomic, antigenic, and biochemical profiles. (Hepatology 2008;48:1598–1607.)
Multiple Small Pulmonary Arteriovenous Fistulas
Authors: J. S. SANDERS, J. M. MARTT
Journal: Circulation (1962)

The condition of multiple small pulmonary arteriovenous fistulas is discussed with regard to diagnosis, complications, and possible etiology. The lesions are believed to be either congenital in origin or secondary to cirrhosis of the liver with portal hypertension. Surgical therapy has not been attempted in this condition because of the diffuse nature of the lesions. A case is discussed wherein the diagnosis of diffuse small pulmonary arteriovenous fistulas was made by cardiac catheterization. The catheter was passed through an atrial septal defect into a pulmonary vein. Difference in oxygen saturation between the pulmonary vein and pulmonary capillaries (pulmonary vein wedge) revealed conclusive evidence of a right-to-left shunt in this area. Etiologic and therapeutic considerations are discussed in view of recent literature on this subject.
Notch and NF-kB signaling pathways regulate miR-223/FBXW7 axis in T-cell acute lymphoblastic leukemia
Authors: V Kumar, R Palermo, C Talora, A F Campese, S Checquolo, D Bellavia, L Tottone, G Testa, E Miele, S Indraccolo, A Amadori, E Ferretti, A Gulino, A Vacca, I Screpanti
Journal: Leukemia (2014)
In vitro and in vivo effects of leukotriene B4 antagonism in a primate model of asthma.
Authors: C R Turner, R Breslow, M J Conklyn, C J Andresen, D K Patterson, A Lopez-Anaya, B Owens, P Lee, J W Watson, H J Showell
Journal: Journal of Clinical Investigation (1996)

To test the hypothesis that leukotriene (LT) B4 antagonists may be clinically useful in the treatment of asthma, CP-105,696 was evaluated in vitro, using chemotaxis and flow cytometry assays, and in vivo, using a primate asthma model. CP-105,696 inhibited LTB4-mediated monkey neutrophil chemotaxis (isolated cells, LTB4 = 5 nM) and CD11b upregulation (whole blood, LTB4 = 100 nM) with IC50 values of 20 nM and 16.5 microM, respectively. Using a modification of a previously described in vivo protocol (Turner et al. Am. J. Respir. Crit. Care Med. 1994. 149: 1153-1159), we observed that treatment with CP-105,696 inhibited the acute increase in bronchoalveolar lavage (BAL) levels of IL-6 and IL-8 by 56.9 +/- 13.2% and 46.9 +/- 14.5%, respectively, 4 h after challenge with Ascaris suum antigen (Ag). CP-105,696 tended to reduce the increase in BAL protein levels 0.5 h after Ag challenge by 47.5 +/- 18.3%, but this was not statistically significant. In addition, CP-105,696 prevented the significant 11-fold increase in airway responsiveness to methacholine after multiple Ag challenge. These results suggest that LTB4 partially mediates acute and chronic responses to antigen in an experimental primate asthma model and support the clinical evaluation of LTB4 antagonists in human asthma.
Protein kinase-dependent Cl- currents in feline ventricular myocytes.
Authors: K Zhang, P L Barrington, R L Martin, R E Ten Eick
Journal: Circulation Research (1994)

A Cl- current (ICl) induced by isoproterenol (ISO) has been identified in isolated guinea pig ventricular myocytes. This ISO-induced ICl can be inhibited by propranolol and mimicked by forskolin (FSK), suggesting that beta-receptors, cAMP, and protein kinase A (PKA) are involved in regulating the involved Cl- channel. Because activation of protein kinase C (PKC) mediated via alpha-adrenergic receptor stimulation is also known to regulate several ion channels, the idea that activation of PKC also can induce ICl was investigated by using isolated feline ventricular myocytes and the whole-cell patch-clamp technique. We found that extracellularly applied phorbol 12-myristate 13-acetate (PMA) could activate ICl in feline ventricular cells. Control experiments indicated that in the absence of PMA or other interventions, the steady-state current-voltage relation of patches maintained for more than 40 minutes was unchanged over a voltage range from -100 to +80 mV. This suggests that the present findings are not complicated by the development over time after patching of a steady-state ICl, similar to the findings reported for canine atrial myocytes. When induced by PMA, ICl was noninactivating and outwardly rectifying; it reversed polarity at approximately the equilibrium potential for Cl- and was sensitive to the Cl- channel blocker 9-anthracene carboxylic acid. In contrast, PMA failed to induce ICl when either staurosporine or calphostin C was added to the patch pipette solution used to internally dialyze the myocytes. The kinetic properties of PMA- and FSK-induced ICl were similar. When supramaximal concentrations of both ISO (1 mumol/L) and PMA (6 mumol/L) were applied simultaneously, the size of the induced ICl was the same as that induced by the same concentrations of either agonist applied alone. In addition, maximal induction of ICl with PMA (6 mumol/L) prevented the effects of FSK (1 mumol/L, the concentration causing approximately 40% of the maximal response [approximately EC40]), yet the effects of simultaneously applied submaximal concentrations (eg, approximately EC25 to approximately EC40) of both 0.5 mumol/L PMA and 1 mumol/L FSK were roughly additive. The results suggest that (1) both PMA and ISO or FSK can induce ICl with approximately equal efficacy, (2) the PMA- and ISO- or FSK-induced ICls are similar, and (3) they all flow through the same set of Cl- channels, implying that channel phosphorylation via either PKA or PKC can activate this feline cardiac ICl.
E-cigarettes: the best and the worst case scenarios for public health--an essay by Simon Chapman
Authors: S. Chapman
Journal: BMJ (2014)

Considerable energy is going into envisioning the likely benefits and harms of the proliferation of e-cigarettes, the use of which is growing exponentially in some countries. <b>Simon Chapman</b> reflects on two possible long term patterns of use and argues that we must not repeat the mistakes with the way in which tobacco was sold and marketed
Paediatric pseudoxanthoma elasticum with cardiovascular involvement
Authors: Q. Li, J. Baker, J. Kowalczyk, Q. Jiang, J. Uitto, L. Schachner
Journal: British Journal of Dermatology (2013)

Pseudoxanthoma elasticum (PXE) is characterized by aberrant mineralization of connective tissues, causing considerable morbidity and mortality. The disease is typically of late onset, the skin manifestations first being noted in the teens or later. Another aberrant mineralization disorder, generalized arterial calcification of infancy (GACI), is present at birth and can demonstrate a phenotypic overlap with PXE.A patient with PXE was noted to have skin findings as early as at 6 years of age, with cardiovascular involvement. The purpose of this study was to examine the genetic basis of this phenotypic presentation in the spectrum of PXE/GACI.The patient's genotype was studied by sequencing ABCC6 and ENPP1, genes known to be associated with PXE and/or GACI.Screening of the ABCC6 gene revealed two pathogenetic mutations, p.R1141X and g.del23-29. Analysis of the ENPP1 gene failed to demonstrate the presence of mutations.This study demonstrates the presence of cutaneous findings of PXE in an 8-year-old paediatric patient, with cardiovascular involvement, illustrating the phenotypic spectrum of PXE.
A common-source outbreak of fulminant hepatitis B in hemodialysis patients induced by precore mutant
Authors: Satoshi Tanaka, Makoto Yoshiba, Shiro Iino, Masako Fukuda, Haruhisa Nakao, Fumio Tsuda, Hiroaki Okamoto, Yuzo Miyakawa, Makoto Mayumi
Journal: Kidney International (1995)
Methicillin-Resistant Staphylococcus aureus Osteomyelitis in a Neonate
Authors: Janis L. Weeks
Journal: JAMA (1981)

METHICILLIN-resistant strains of<i>Staphylococcus aureus</i>were first reported from the United States as early as 1960. However, outbreaks of nosocomial infections caused by these organisms, usually involving adult patients, have only recently been reported.<sup>1,2</sup>Such an outbreak associated with<i>S aureus</i>resistant to methicillin, the cephalosporins, erythromycin, lincomycin, clindamycin, and kanamycin occurred among neonates housed in the intermediate and intensive care nurseries of our city-county hospital during the summer of 1979. The index patient had persistent bacteremia and multiple bone osteomyelitis that were successfully treated with gentamicin and vancomycin. <h3>Report of a Case</h3> A 1.0-kg male infant was born to an apparently healthy 20-year-old mother. Gestational age was 22 weeks by history and 30 weeks by physical examination. The pregnancy was uncomplicated. Ventilatory support was required for the first two days of life for transient tachypnea of the newborn and apnea. An umbilical arterial catheter (UAC), placed shortly after
The Maker of a New Instrument.
Authors: C. L. Smith
Journal: JAMA (1897)

Aurora, Ill., Sept. 2, 1897. <h3>To the Editor:</h3> —Since the publication of my article in theJournalon "A New Curette," I have been in receipt of numerous inquiries as to where the instrument is made. A footnote in the original article stated that it was to be made by Sharp &amp; Smith, but, I presume from some oversight, was omitted. I shall deem it a great favor if you will make a note as to who the makers are in the next issue of theJournal. Sincerely,
Spectrum Bias in the Evaluation of Diagnostic Tests: Lessons from the Rapid Dipstick Test for Urinary Tract Infection
Authors: Mark S. Lachs, Irving Nachamkin, Paul H. Edelstein, Jay Goldman, Alvan R. Feinstein, J. Sanford Schwartz
Journal: Annals of Internal Medicine (1992)

▪ Objective: To determine if the leukocyte esterase and bacterial nitrite rapid dipstick test for urinary tract infection (UTI) is susceptible to spectrum bias (when a diagnostic test has different sensitivities or specificities in patients with different clinical manifestations of the disease for which the test is intended). ▪ Design: Cross-sectional study. ▪ Patients: A total of 366 consecutive adult patients in whom clinicians performed urinalysis to diagnose or exclude UTI. ▪ Setting: An urban emergency department and walk-in clinic. ▪ Measurements: After the patient encounter, but before dipstick test or culture was done, clinicians recorded the signs and symptoms that were the basis for suspecting UTI and for performing a urinalysis and an estimate of the probability of UTI based on the clinical evaluation. For all patients who received urinalysis, dipstick tests and culture were done in the clinical microbiology laboratory by medical technologists blinded to clinical evaluation. Sensitivity for the dipstick was calculated using a positive result in either leukocyte esterase or bacterial nitrite, or both, as the criterion for a positive dipstick, and greater than 105 CFU/mL for a positive culture. ▪ Results: In the 107 patients with a high (>50%) prior probability of UTI, who had many characteristic UTI symptoms, the sensitivity of the test was excellent (0.92; 95% Cl, 0.82 to 0.98). In the 259 patients with a low (≤50%) prior probability of UTI, the sensitivity of the test was poor (0.56; Cl, 0.03 to 0.79). ▪ Conclusions: The leukocyte esterase and bacterial nitrite dipstick test for UTI is susceptible to spectrum bias, which may be responsible for differences in the test's sensitivity reported in previous studies. As a more general principle, diagnostic tests may have different sensitivities or specificities in different parts of the clinical spectrum of the disease they purport to identify or exclude, but studies evaluating such tests rarely report sensitivity and specificity in subgroups defined by clinical symptoms. When diagnostic tests are evaluated, information about symptoms in the patients recruited for study should be included, and analyses should be done within appropriate clinical subgroups so that clinicians may decide if reported sensitivities and specificities are applicable to their patients.
Sedation, Alimentation, Hydration, and Equivocation: Careful Conversation about Care at the End of Life
Authors: Lynn A. Jansen, Daniel P. Sulmasy
Journal: Annals of Internal Medicine (2002)

In the recent medical ethics literature, several authors have recommended terminal sedation and refusal of hydration and nutrition as important, morally acceptable, and relatively uncontroversial treatment options for end-of-life suffering. However, not all authors use these terms to refer to the same practices. This paper examines the various ways that the terms terminal sedation and refusal of hydration and nutrition have been used in the medical literature. Although some of these practices are ethically appropriate responses to end-of-life suffering, others (at least as they are currently described in the medical ethics literature) are not. This paper identifies and discusses the principles that morally distinguish these practices from one another and specifically describes different features of medical practices and moral principles that affect the moral acceptability of various medical treatments. These distinctions reveal the complexity of the issues surrounding terminal sedation and refusal of hydration and nutrition, a complexity that has not been adequately addressed in recent discussions.
Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage
Authors: Tara E Sutherland, Nicola Logan, Dominik Rückerl, Alison A Humbles, Stuart M Allan, Venizelos Papayannopoulos, Brigitta Stockinger, Rick M Maizels, Judith E Allen
Journal: Nature Immunology (2014)
Treatment of Partial Priapism With an Intracavernous Injection of Etilefrine
Authors: Walter Albrecht
Journal: JAMA (1997)

<h3>To the Editor.</h3> —Partial priapism affects the proximal penis and is rare. Only 7 such cases have been reported,<sup>1</sup>and all have been treated surgically. Etilefrine, a sympathomimetic drug available in much of Europe but not the United States, has been used as an intracavernous injection in the treatment of classic priapism.<sup>2,3</sup>This is the first report of successful treatment of partial priapism by an intracavernous injection of the vasoactive drug etilefrine. <h3>Report of a Case.</h3> —A 29-year-old man presented with a perineal mass causing discomfort. The symptoms began 4 days prior to admission and were associated with impotence. No trauma or other unusual event was reported. He gave no history of similar episodes and denied taking drugs known to cause priapism.<sup>2</sup> Physical examination revealed a painless perineal mass of elastic consistency involving the penoscrotal junction and extending along the right proximal corpus cavernosum. The distal penis
Adding renal dysfunction to CHADS<sub>2</sub>did not improve prediction of stroke or systemic embolism in AF
Authors: Catherine M. Clase, Deborah L. Zimmerman, Benjamin K. A. Thomson
Journal: Annals of Internal Medicine (2013)

Source Citation Piccini JP, Stevens SR, Chang Y, et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R2CHADS2 index in the ROCKET and ATRIA study cohorts. Circulation. 2013;127:224-32. 23212720
Cost-Effectiveness of Alternative Management Strategies for Patients with Solitary Pulmonary Nodules
Authors: Michael K. Gould, Gillian D. Sanders, Paul G. Barnett, Chara E. Rydzak, Courtney C. Maclean, Mark B. McClellan, Douglas K. Owens
Journal: Annals of Internal Medicine (2003)

Background: Positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) is a potentially useful but expensive test to diagnose solitary pulmonary nodules. Objective: To evaluate the cost-effectiveness of strategies for pulmonary nodule diagnosis and to specifically compare strategies that did and did not include FDG-PET. Design: Decision model. Data Sources: Accuracy and complications of diagnostic tests were estimated by using meta-analysis and literature review. Modeled survival was based on data from a large tumor registry. Cost estimates were derived from Medicare reimbursement and other sources. Target Population: All adult patients with a new, noncalcified pulmonary nodule seen on chest radiograph. Time Horizon: Patient lifetime. Perspective: Societal. Intervention: 40 clinically plausible combinations of 5 diagnostic interventions, including computed tomography, FDG-PET, transthoracic needle biopsy, surgery, and watchful waiting. Outcome Measures: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Results of Base-Case Analysis: The cost-effectiveness of strategies depended critically on the pretest probability of malignancy. For patients with low pretest probability (26%), strategies that used FDG-PET selectively when computed tomography results were possibly malignant cost as little as $20 000 per QALY gained. For patients with high pretest probability (79%), strategies that used FDG-PET selectively when computed tomography results were benign cost as little as $16 000 per QALY gained. For patients with intermediate pretest probability (55%), FDG-PET strategies cost more than $220 000 per QALY gained because they were more costly but only marginally more effective than computed tomography-based strategies. Results of Sensitivity Analysis: The choice of strategy also depended on the risk for surgical complications, the probability of nondiagnostic needle biopsy, the sensitivity of computed tomography, and patient preferences for time spent in watchful waiting. In probabilistic sensitivity analysis, FDG-PET strategies were cost saving or cost less than $100 000 per QALY gained in 76.7%, 24.4%, and 99.9% of computer simulations for patients with low, intermediate, and high pretest probability, respectively. Conclusions: FDG-PET should be used selectively when pretest probability and computed tomography findings are discordant or in patients with intermediate pretest probability who are at high risk for surgical complications. In most other circumstances, computed tomography-based strategies result in similar quality-adjusted life-years and lower costs.
Invasive Pulmonary Aspergillosis
Authors: Robert J. Carabasi
Journal: JAMA (1980)

<h3>To the Editor:—</h3> In reference to the article "Invasive Pulmonary Aspergillosis Associated With Influenza" by Fischer and Walker (241:1493, 1979), mention is made that invasive pulmonary aspergillosis is usually seen in the compromised host and that invasive disease is rare in normal persons. The authors mention only 13 cases of pulmonary aspergillosis being described in the literature as occurring in normal hosts. In 1961, my coauthors and I<sup>1</sup>reported an additional case that was not cited by Drs Fischer and Walker.