tbuckley/cabot-search huggingface dataset:
Electrophysiologic characteristics of sudden QRS axis deviation during orthodromic tachycardia. Role of functional fascicular block in localization of accessory pathway.
Authors: M R Jazayeri, J Caceres, P Tchou, R Mahmud, S Denker, M Akhtar
Journal: Journal of Clinical Investigation (1989)

We analyzed the effect of functional fascicular block (FFB) on ventriculoatrial conduction time (VACT) during orthodromic tachycardia (OT) in 32 patients with single accessory pathway (AP) of the Kent bundle type. The location of AP was left free wall (LFW-AP) in 21 patients, left posteroseptal in 6, right free wall in 2, and right anteroseptal in 3. FFB either alone or in combination with functional left or right bundle branch block (LBBB or RBBB) occurred predominantly at the onset of OT and was initiated with ventricular extrastimulus technique more often than with atrial extrastimulation. In patients with LFW-AP, isolated functional left anterior fascicular block (LAFB) produced significant prolongation in VACT (15-35 ms). A similar magnitude of VACT increase (20-35 ms) was also observed when LAFB was associated with RBBB. Although 25-45-ms prolongation in VACT occurred with functional LBBB and normal axis, an additional 20-55-ms VACT increase was seen when LAFB accompanied LBBB. Functional LAFB, alone or in combination with bundle branch block, however, did not prolong VACT in patients with other AP locations. Furthermore, left posterior fascicular block did not produce prolongation of VACT in any of the cases. It is concluded that in patients with the Wolff-Parkinson-White syndrome, evaluation of VACT during functional LAFB provides important information regarding AP localization and a clear separation of LFW-AP from all other locations.
Abnormal regulation of renal vitamin D catabolism by dietary phosphate in murine X-linked hypophosphatemic rickets.
Authors: H S Tenenhouse, G Jones
Journal: Journal of Clinical Investigation (1990)

Hyp mice exhibit increased renal catabolism of vitamin D metabolites by the C-24 oxidation pathway (1988. J. Clin. Invest. 81:461-465). To examine the regulatory influence of dietary phosphate on the renal vitamin D catabolic pathway in Hyp mice, we measured C-24 oxidation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in renal mitochondria isolated from Hyp mice and normal littermates fed diets containing 0.03% (low-Pi), 1% (control-Pi), and 1.6% (high-Pi) phosphate. In normal mice the low-Pi diet led to a rise in serum 1,25(OH)2D (22.2 +/- 1.8 to 48.1 +/- 6.8 pg/ml, P less than 0.05) and no change in C-24 oxidation products (0.053 +/- 0.006 to 0.066 +/- 0.008 pmol/mg protein per min) when compared with the control diet. In Hyp mice the low-Pi diet elicited a fall in serum 1,25(OH)2D (21.9 +/- 1.2 to 8.0 +/- 0.2 pg/ml, P less than 0.05) and a dramatic increase in C-24 oxidation products (0.120 +/- 0.017 to 0.526 +/- 0.053 pmol/mg protein per min, P less than 0.05) when compared with the control diet. The high-Pi diet did not significantly alter serum levels of 1,25(OH)2D or C-24 oxidation products in normal mice. Hyp mice on the high-Pi diet experienced a rise in serum 1,25(OH)2D (21.9 +/- 1.2 to 40.4 +/- 7.3, P less than 0.05) and a fall in C-24 oxidation products (0.120 +/- 0.017 to 0.043 +/- 0.007 pmol/mg protein per min, P less than 0.05). The present results demonstrate that the defect in C-24 oxidation of 1,25(OH)2D3 in Hyp mice is exacerbated by phosphate depletion and corrected by phosphate supplementation. The data suggest that the disorder in vitamin D metabolism in the mutant strain is secondary to the perturbation in phosphate homeostasis.
The Epidemiology of Prescriptions Abandoned at the Pharmacy
Authors: William H. Shrank, Niteesh K. Choudhry, Michael A. Fischer, Jerry Avorn, Mark Powell, Sebastian Schneeweiss, Joshua N. Liberman, Timothy Dollear, Troyen A. Brennan, M. Alan Brookhart
Journal: Annals of Internal Medicine (2010)

Background: Picking up prescriptions is an essential but previously unstudied component of adherence for patients who use retail pharmacies. Understanding the epidemiology and correlates of prescription abandonment may have an important effect on health care quality. Objective: To evaluate the rates and correlates of prescription abandonment. Design: Cross-sectional cohort study. Setting: One large retail pharmacy chain and one large pharmacy benefits manager (PBM) in the United States. Measurements: Prescriptions bottled at the retail pharmacy chain between 1 July 2008 and 30 September 2008 by patients insured by the PBM were identified. Pharmacy data were used to identify medications that were bottled and either dispensed or returned to stock (RTS) or abandoned. Data from the PBM were used to identify previous or subsequent dispensing at any pharmacy. The first (index) prescription in a class for each patient was assigned to 1 of 3 mutually exclusive outcomes: filled, RTS, or RTS with fill (in the 30 days after abandonment, the patient purchased a prescription for a medication in the same medication class at any pharmacy). Outcome rates were assessed by drug class, and generalized estimating equations were used to assess patient, neighborhood, insurance, and prescription characteristics associated with abandonment. Results: 10 349 139 index prescriptions were filled by 5 249 380 patients. Overall, 3.27% of index prescriptions were abandoned; 1.77% were RTS and 1.50% were RTS with fill. Patients were least likely to abandon opiate prescriptions. Prescriptions with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40 times and 4.68 times more likely, respectively, to be abandoned than prescriptions with no copayment (P < 0.001 for both comparisons). New users of medications had a 2.74 times greater probability of abandonment than prevalent users (P < 0.001), and prescriptions delivered electronically were 1.64 times more likely to be abandoned than those that were not electronic (P < 0.001). Limitation: The study included mainly insured patients and analyzed data collected during the summer months only. Conclusion: Although prescription abandonment represents a small component of medication nonadherence, the correlates to abandonment highlight important opportunities to intervene and thereby improve medication taking. Primary Funding Source: CVS Caremark.
Immunogenicity and safety of the influenza A H1N1v 2009 vaccine in cancer patients treated with cytotoxic chemotherapy and/or targeted therapy: the VACANCE study
Authors: B. Rousseau, P. Loulergue, O. Mir, A. Krivine, S. Kotti, E. Viel, T. Simon, A. de Gramont, F. Goldwasser, O. Launay, C. Tournigand
Journal: Annals of Oncology (2011)
Improving Medication Adherence and Helping Patients Make Lifestyle Changes
Authors: Ronald S. Banner
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Genistein Increases the Sensitivity of Cardiac Ion Channels to β-Adrenergic Receptor Stimulation
Authors: Livia C. Hool, Lisa M. Middleton, Robert D. Harvey
Journal: Circulation Research (1998)

Abstract —The whole-cell patch-clamp technique was used to monitor the effects of genistein, a tyrosine kinase inhibitor, on membrane currents recorded from isolated guinea pig ventricular myocytes. Under control conditions, genistein (50 μmol/L) did not activate the latent cAMP-regulated Cl − current ( I Cl ). However, in the presence of a subthreshold concentration (1 nmol/L) of the β-adrenergic agonist isoproterenol (Iso), genistein caused a near-maximal activation of this current. In the absence of genistein, Iso activated I Cl with an EC 50 of 5 nmol/L. In the presence of genistein, Iso activated I Cl with an EC 50 of 0.3 nmol/L. This facilitatory effect was not observed in the presence of daidzein (50 μmol/L), an analogue of genistein that only weakly inhibits tyrosine kinase activity. Furthermore, peroxovanadate, a potent inhibitor of phosphotyrosine phosphatase activity, inhibited I Cl activated by Iso alone, and it blocked the stimulatory effect of genistein in the presence of Iso. To determine whether the stimulatory effect of genistein was specific for I Cl , we also studied its action on the cAMP-regulated delayed rectifier K + current ( I K ) and L-type Ca 2+ current ( I Ca-L ) present in these cells. Basal I K and I Ca-L were partially (≈30% to 40%) inhibited by genistein. However, this inhibitory effect was mimicked by daidzein, suggesting that inhibition of tyrosine kinase activity is not involved. In addition to the nonspecific inhibitory effect, genistein also caused a significant increase in the β-adrenergic sensitivity of the unblocked cationic currents. In the absence of genistein, 1 nmol/L Iso had no effect on either I K or I Ca-L . However, in the presence of genistein, 1 nmol/L Iso significantly increased the magnitude of both currents. These results suggest that tyrosine kinase activity may play an important role in regulating β-adrenergic responsiveness of the heart.
Caffeine reversal of length-dependent changes in myocardial contractile state in the cat.
Authors: L H Chuck, W W Parmley
Journal: Circulation Research (1980)

The present study evaluated potential mechanisms for the slow length-dependent change in myocardial contractile state. Using 40 isolated right ventricular cat papillary muscles, we found that 10 mM caffeine reversed the subsequent slow change in myocardial performance following a change in muscle length. Since caffeine acts both at the sarcolemma and the sarcoplasmic reticulum, we attenuated the sarcolemmal influx of calcium with verapamil, manganese, and low external calcium concentration. None of these interventions altered the caffeine reversal of the length-dependent effect. It thus appears that the length-dependent alteration of contractile state is of intracellular origin, and probably related to altered calcium handling by the sarcoplasmic reticulum.
β1 Integrin/FAK/cortactin signaling is essential for human head and neck cancer resistance to radiotherapy
Authors: Iris Eke, Yvonne Deuse, Stephanie Hehlgans, Kristin Gurtner, Mechthild Krause, Michael Baumann, Anna Shevchenko, Veit Sandfort, Nils Cordes
Journal: Journal of Clinical Investigation (2012)

Integrin signaling critically contributes to the progression, growth, and therapy resistance of malignant tumors. Here, we show that targeting of β₁ integrins with inhibitory antibodies enhances the sensitivity to ionizing radiation and delays the growth of human head and neck squamous cell carcinoma cell lines in 3D cell culture and in xenografted mice. Mechanistically, dephosphorylation of focal adhesion kinase (FAK) upon inhibition of β₁ integrin resulted in dissociation of a FAK/cortactin protein complex. This, in turn, downregulated JNK signaling and induced cell rounding, leading to radiosensitization. Thus, these findings suggest that robust and selective pharmacological targeting of β₁ integrins may provide therapeutic benefit to overcome tumor cell resistance to radiotherapy.
Cholesterol accumulation and liver cell death in mice with Niemann-Pick type C disease
Authors: Eduardo P. Beltroy, James A. Richardson, Jay D. Horton, Stephen D. Turley, John M. Dietschy
Journal: Hepatology (2005)

Abstract Niemann-Pick type C (NPC) disease develops as a result of mutations in the NPC1 gene that encodes a protein involved in the net movement of unesterified cholesterol from the late endosomal/lysosomal compartment to the metabolically active pool of sterol in the cytosol of virtually every cell in the body. Although early publications emphasized the neurodegeneration occurring in children with this mutation, more recent clinical information suggests that serious liver disease also is an important part of this syndrome. These studies, therefore, were undertaken to characterize the liver dysfunction seen in mice with this same mutation. The NPC mouse develops significant hepatomegaly that reaches 8% of body weight at 5 to 6 weeks of age. This increase in liver size is associated with a linear increase in cholesterol content and with accumulation of amorphous cellular inclusions in both hepatocytes and macrophages. During the few weeks after birth, significant elevation of the plasma alkaline phosphatase level occurs, as also is seen in the human infant with this disease. At 4 to 5 weeks of age, plasma aminotransferase levels also rise abruptly. Histologically, at this time there is apoptosis, but no excess deposition of collagen or glycogen. mRNA expression is elevated for caspase 1, caspase 6, and several enzymes associated with sterol biosynthesis and bile acid formation. In conclusion , the NPC mouse has liver disease similar to that seen in the NPC infant and represents a relevant model for exploring the molecular events occurring in this form of liver disease. (Hepatology 2005;42:886–893.)
Can transmissible strains of Pseudomonas aeruginosa be successfully eradicated?
Authors: F.J. Gilchrist, M. France, R. Bright-Thomas, C.J. Doherty, J.R. Govan, A.K. Webb, A.M. Jones
Journal: European Respiratory Journal (2011)

Although antibacterial (e.g.cefepime, cefoperazone/sulbactam and moxifloxacin) and antifungal agents (itraconazole) were administered intravenously according to the microbiological results, the patient had no response and finally died of respiratory failure after a 28-day ICU stay.The isolation of G100 was unlikely to have been due to contamination, based on the following observations.First, the isolation of Ralstonia spp.from clinical samples is extremely rare at our centre and no other cultures in West China Hospital grew Ralstonia spp. in this year.Secondly, no saline solutions or water were used to collect the sputum sample, which was collected prior to noninvasive ventilation.Thirdly, Gram-negative rods were detected in the sputum by microscopy.As G100 was recovered from a sample collected on admission and this patient had no recent history of hospitalisation, this isolate probably had a community origin.After administration of piperacillin/tazobactam, no R. mannitolilytica was isolated from sputum samples collected from this patient afterwards, but the patient's condition did not improve.This suggests that G100 was probably not the causative agent, or at least, not the sole causative agent of the acute exacerbation of COPD in this patient.It is more likely that R. mannitolilytica had colonised in the respiratory tract in this case.R. mannitolilytica has been recovered from the respiratory tract of patients with cystic fibrosis [6].However, cystic fibrosis is not common in China and this patient did not have this disease.As microbial colonisation of airways could lead to exacerbations of COPD, the isolation of R. mannitolilytica in the respiratory tract of the COPD patient could be of clinical importance.As misidentification is common, R. mannitolilytica might be an overlooked member of the bacterial flora in the respiratory tract of COPD patients.Ralstonia spp.(identified as R. pickettii, but without describing the method for identification) have previously been found to cause COPD exacerbation [9].Nonetheless, our report describes a rare case of R. mannitolilytica associated with a COPD patient and, to our knowledge, this case is the first identification of R. mannitolilytica from clinical samples in mainland China.
Cognitive function in COPD
Authors: J. W. Dodd, S. V. Getov, P. W. Jones
Journal: European Respiratory Journal (2010)

In order to characterise the overall clinical picture of chronic obstructive pulmonary disease (COPD) a better understanding of all relevant comorbidities is required. It is increasingly recognised that COPD is a multi-component disease, but little attention has been paid to its effects on cognitive function. Cognitive dysfunction is associated with increased mortality and disability; however, it remains poorly understood in COPD. This review examines mechanisms of injury and dysfunction to the brain and considers the methods used to evaluate cognition, and assembles evidence concerning the nature and level of cognitive impairment in COPD. Our main findings are: 1) there may be a pattern of cognitive dysfunction specific to COPD; 2) cognitive function is only mildly impaired in patients without hypoxaemia; 3) the incidence of cognitive dysfunction is higher in hypoxaemia; 4) hypoxaemia, hypercapnia, smoking and comorbidities (such as vascular disease) are unlikely to account for all of the cognitive dysfunction seen in COPD; 5) there is weak or no association between cognitive function and mood, fatigue or health status; 6) cognitive dysfunction may be associated with increased mortality and disability; and 7) there is limited evidence for a significant effect of treatment on cognitive function.
Racial Profiling in Medical Research
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2001)

Two articles in this issue of the Journal deal with the treatment of heart failure in white and black patients. One, concerning carvedilol, reports that the benefit of this beta-blocker is similar in nonblacks and blacks with chronic heart failure.1 The other contends that enalapril, an angiotensin-converting–enzyme inhibitor, is more effective in whites than in blacks with left ventricular dysfunction.2 The authors of both articles refer to “race,” “racial groups,” “racial differences,” and “ethnic background” but offer no plausible biologic justification for making such distinctions. In a nod to the quandary faced by anyone who tries to explain the complex . . .
Development and validation of a questionnaire (FASH—Functional Assessment Scale for Acute Hamstring Injuries): to measure the severity and impact of symptoms on function and sports ability in patients with acute hamstring injuries
Authors: Nikos Malliaropoulos, Vasileios Korakakis, Dimitris Christodoulou, Nat Padhiar, Debasish Pyne, Giannis Giakas, Tanja Nauck, Peter Malliaras, Heinz Lohrer
Journal: British Journal of Sports Medicine (2014)

Objective To develop a condition-specific patient-reported outcome measure, the Functional Assessment Scale for Acute Hamstring Injuries (FASH), de novo in three languages, following distinct and rigorous methodology for content generation, analysis and validation and to assess its psychometric properties. Background To our knowledge, there is no patient-reported functional scale specific for acute hamstring injuries. Methods The development of the scale followed specific guidelines, as well as de novo construction in three languages (Greek, English and German). Item generation was accomplished by selecting three different sources of items: literature review, focus group and key informant interviews. Content analysis was conducted by an expert committee. The 21 items selected as appropriate were tested through a structured content analytic method and item-content validity coefficient, and 10 were retained for the FASH. The validation and assessment of its psychometric properties followed theConsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) recommendations to ensure quality, in a convenience sample of 140 participants. Results The face validity was adequate and tested by expert committees, authors and participants. Content validity was characterised as well addressed and conducted independently by experts and through specific content validation procedures. The dimensionality analysis indicated a one-factor solution explaining the 95.8% of total variance. Known group validity was demonstrated by significant differences between patients and controls (p&lt;0.001). The FASH exhibited very good test–retest reliability (intraclass correlation coefficient=0.9, p&lt;0.001), internal consistency (α=0.98) and responsiveness (3.81 and 5.23 using baseline and pooled SD, respectively; standardised response mean (SRD)=4.68). Conclusion This study provides initial evidence for psychometric properties of the first scale assessing hamstring injuries.
Intrapulmonary transplantation of macrophage progenitors as long-lasting therapy for hereditary pulmonary alveolar proteinosis
Authors: Christine Happle, Nico Lachmann, Jelena Skuljec, Martin Wetzke, Mania Ackermann, Sebastian Brennig, Adele Mucci, Stephanie Groos, Anja Mirenska, Christian Hennig, Thomas Rodt, Jens Bankstahl, Nicolaus Schwerk, Thomas Moritz, Gesine Hansen
Journal: European Respiratory Journal (2014)

Hereditary pulmonary alveolar proteinosis (herPAP) is a rare lung disease caused by mutations in the granulocyte/macrophage-colony-stimulating factor (GM-CSF) receptor genes, resulting in disturbed alveolar macrophage differentiation, massive alveolar proteinosis, and life-threatening respiratory insufficiency. So far, the only effective treatment for herPAP is repetitive whole lung lavage, a merely symptomatic and highly invasive procedure. We introduce intrapulmonary transplantation of macrophage progenitors as a novel, effective and long-lasting therapy for herPAP. In a murine disease model, intrapulmonary transplantation of healthy macrophage progenitors led to selective pulmonary engraftment of functional alveolar macrophages. A single transplantation significantly ameliorated the herPAP phenotype for up to nine months. Treated mice displayed clearly reduced BALF proteinosis, normalized lung densities in computed tomography, and improved lung function. In a second, humanized herPAP model, the therapeutic effect of intrapulmonary administered human macrophage progenitors was evaluated. Here, the transplantation led to a significant and sustained disease resolution that was mediated by long-lived, lung-resident human macrophages. Our findings have direct clinical implications, as they present a novel and causative approach for the treatment of herPAP. Given its simplicity, safety and effectiveness, our approach is not only relevant for herPAP, but may also serve as a proof-of-principle for treatment of other genetic and non-hereditary lung-diseases, expanding current stem cell-based strategies towards potent macrophage-based therapies.
A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency
Authors: A O'Brien, M Blaivas, J Albers, J Wald, C Watts
Journal: European Respiratory Journal (1998)

Mitochondrial myopathy is a rare cause of dyspnoea and respiratory failure, usually presenting in infancy. We describe a 27 yr old woman with a partial cytochrome c oxidase enzyme deficiency causing respiratory muscle weakness and respiratory failure. The onset was acute, with no preceding respiratory symptoms. The patient was successfully treated with bilevel positive airway pressure therapy.