tbuckley/cabot-search huggingface dataset:
Overnight Shift From Obstructive to Central Apneas in Patients With Heart Failure
Authors: Ruzena Tkacova, Mitra Niroumand, Geraldo Lorenzi-Filho, T. Douglas Bradley
Journal: Circulation (2001)

Background —Obstructive (OSA) and central sleep apnea (CSA) can coexist in patients with congestive heart failure (CHF). However, the reason why OSA events occur at one time and CSA events at another has not been determined. We hypothesized that a change in P co 2 would be associated with an alteration in apnea type: a decrease in P co 2 should lead to CSA. Methods and Results —To test this hypothesis, we evaluated minute ventilation (V I ), transcutaneous P co 2 (Ptc co 2 ), circulation time, and periodic breathing cycle length during overnight polysomnography in 12 patients with CHF and coexisting OSA and CSA. V I was significantly greater (mean±SEM, 9.4±1.3 versus 8.0±0.9 L/min; P &lt;0.05) and Ptc co 2 was lower (39.4±1.0 versus 41.9±1.1 mm Hg, P &lt;0.01) during episodes of CSA than of OSA. These changes were associated with significant lengthening of circulation time (23.6±3.7 versus 21.1±3.6 seconds, P &lt;0.01) and periodic breathing cycle length (53.7±3.5 versus 49.6±2.9 seconds, P &lt;0.01). In addition, the proportion of obstructive events decreased (from 68.5±11.4% to 22.5±7.2%, P &lt;0.001) and of CSA events increased (from 31.5±11.4% to 77.5±7.2%, P &lt;0.001) from the first to the last quarter of the night in association with a significant decrease in Ptc co 2 (from 42.6±0.9 to 40.8±0.9 mm Hg, P &lt;0.01). Conclusions —In patients with CHF, the shift from OSA to CSA is associated with a reduction in P co 2 . This appears to be related to an overnight deterioration in cardiac function as suggested by the concurrent lengthening of circulation time. Therefore, in CHF patients, alterations in cardiac function may influence apnea type.
969-97 Regional Strain and Wall Motion of the Transplanted Left Ventricle in Pediatric Patients Using Magnetic Resonance Tagging
Authors: Mary T. Donofrio, Bernard J. Clark, Claudio Ramaciotti, Marshall L. Jacobs, Kenneth E. Fellows, Paul M. Weinberg, Mark A. Fogel
Journal: Journal of the American College of Cardiology (1995)
Respiratory Viral Infections in Adults With and Without Chronic Obstructive Pulmonary Disease
Authors: STEPHEN B. GREENBERG, MARTHA ALLEN, JOAN WILSON, ROBERT L. ATMAR
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

A longitudinal cohort study of older adults with chronic obstructive pulmonary disease (COPD) who were stratified by FEV1 at enrollment was done to define the etiology, frequency, severity, and medical-care impact of respiratory tract viral infections (RTVIs). Controls consisted of a group of subjects of comparable age with the patients. RTVIs were documented in 44% of observed acute respiratory illnesses in control subjects and in 27% of COPD subjects, who were followed for mean periods of 35 and 26 mo, respectively. In this heavily influenza-vaccinated cohort ( ∼ 90% vaccinated each year), picornaviruses, parainfluenza viruses, and coronaviruses were most commonly identified. Mean time to return to clinical baseline was approximately 2 wk in each group. Control and COPD subjects with mild airways obstruction (baseline FEV1 ⩾ 50% predicted) had few emergency-center visits or hospitalizations. Approximately half of COPD subjects with moderate/severe COPD (baseline FEV1 < 50% predicted) had at least one emergency-center visit and/or hospitalization for acute respiratory illness. RTVIs were documented in 23% of hospitalizations and in 45% of patients admitted between December and March. RTVIs have a major impact on utilization of health care resources for COPD patients with moderate/severe airways obstruction.
The pharmacological impact of ATP-binding cassette drug transporters on vemurafenib-based therapy
Authors: Chung-Pu Wu, Suresh V. Ambudkar
Journal: Acta Pharmaceutica Sinica B (2014)

Melanoma is the most serious type of skin cancer and one of the most common cancers in the world. Advanced melanoma is often resistant to conventional therapies and has high potential for metastasis and low survival rates. Vemurafenib is a small molecule inhibitor of the BRAF serine-threonine kinase recently approved by the United States Food and Drug Administration to treat patients with metastatic and unresectable melanomas that carry an activating BRAF (V600E) mutation. Many clinical trials evaluating other therapeutic uses of vemurafenib are still ongoing. The ATP-binding cassette (ABC) transporters are membrane proteins with important physiological and pharmacological roles. Collectively, they transport and regulate levels of physiological substrates such as lipids, porphyrins and sterols. Some of them also remove xenobiotics and limit the oral bioavailability and distribution of many chemotherapeutics. The overexpression of three major ABC drug transporters is the most common mechanism for acquired resistance to anticancer drugs. In this review, we highlight some of the recent findings related to the effect of ABC drug transporters such as ABCB1 and ABCG2 on the oral bioavailability of vemurafenib, problems associated with treating melanoma brain metastases and the development of acquired resistance to vemurafenib in cancers harboring the BRAF (V600E) mutation.
Diagnostic accuracy of exercise ECG lead systems in clinical subsets of women.
Authors: P Guiteras, B R Chaitman, D D Waters, M G Bourassa, J M Scholl, R J Ferguson, P Wagniart
Journal: Circulation (1982)

The diagnostic accuracy of 14-lead exercise electrocardiography was evaluated in 112 women who had no history of myocardial infarction and underwent coronary angiography. The sensitivity of ST-segment displacement of 0.1 mV or more in any of 14 ECG leads was 0.79 for coronary artery stenosis of at least 70%; the specificity was 0.66. Results were similar using bipolar ECG leads CC5 and CM5 or 11 standard ECG leads. The ST-segment shifts that occurred only during exercise were associated with a 77% false-positive rate (10 of 13). Downsloping ST-segment depression did not provide more diagnostic information than horizontal ST-segment depression in the three clinical subsets of women. In women with typical angina pectoris, ST-segment depression of at least 0.15 mV for 0.08 second after the J point or a final treadmill time less than 360 seconds was predictive of proximal left or multivessel coronary artery disease. In the women with probable angina or nonspecific chest pain, this finding was not of diagnostic value. ST-segment elevation of 0.1 mV or more in leads V1-2 or a VL predicted proximal stenosis of at lest 80% in the left anterior descending coronary artery in all six women with typical angina pectoris. Maximal exercise testing in women with typical angina provides important diagnostic information when 11 standard ECG leads are recorded. In women with probable angina or nonspecific chest pain, diagnostic exercise testing is less useful and bipolar leads CC5 and CM5 are sufficient for most clinical purposes.
Abstract 5488: Everolimus inhibits the proliferation of aromatase inhibitor-resistant breast cancer cells
Authors: Asona Lui, Joan Lewis-Wambi
Journal: Cancer Research (2014)

Abstract Aromatase inhibitors (AIs) are currently the standard treatment for estrogen receptor positive breast cancer in postmenopausal women. Unfortunately, the majority of patients treated with AIs eventually develop resistance to these drugs. The mechanism by which AI resistance occurs is still not known, however, there is strong evidence that upregulation of the PI3K/Akt/mTOR pathway might play an important role. As such, mTOR inhibition is now under study in clinical trials as a breast cancer treatment. The newest mTOR inhibitor, Everolimus (Afinitor®), has been FDA approved for the treatment of metastatic breast cancer. We have previously reported the development of two AI-resistant breast cancer cell lines (MCF-7:5C and MCF-7:2A) which were clonally derived from parental MCF-7 cells following long term estrogen deprivation. Both MCF-7:5C and MCF-7:2A cells have been shown to overexpress members of the PI3K/Akt/mTOR pathway. In this study, we examined the therapeutic benefits of everolimus in AI-resistant MCF-7:5C and MCF-7:2A cells compared to endocrine sensitive MCF-7 breast cancer cells and normal breast epithelium MCF10A cells. Results from cell viability assay showed that everolimus markedly inhibited the proliferation of endocrine sensitive MCF-7 cells and AI-resistant MCF-7:5C and MCF-7:2A cells in a time-dependent and concentration-dependent manner with IC50s of 30 nM, 40 nM and 10 nM, respectively. Notably, the MCF-7:2A cells were the most sensitive to everolimus which caused a 70% reduction in proliferation at 24 hours whereas in MCF-7 and MCF-7:5C cells only 30% inhibition was observed at the same time point. The inhibitory effect of everolimus was due primarily to G1 arrest and was associated with significant downregulation of phospho-mTOR, phospho-p70S6K, phospho-Akt, GSK3β, cyclin D1 and p21. Colony formation assay in soft agar indicated that AI-resistant MCF-7:5C and MCF-7:2A cells formed significantly more colonies than MCF-7 cells and that treatment with everolimus notably reduced the size and number of colonies for all three cell lines. Finally, we found that exposure of AI-resistant MCF-7:5C and MCF-7:2A cells to a single dose of gamma-irradiation (6 Gy) significantly enhanced the anti-proliferative effect of everolimus on these cells. In summary, these studies showed that everolimus significantly inhibited the proliferation and tumorigenicity of AI-resistant breast cancer cells and that everolimus might be an effective treatment option for patients with AI-resistant breast cancer. Citation Format: Asona Lui, Joan Lewis-Wambi. Everolimus inhibits the proliferation of aromatase inhibitor-resistant breast cancer cells. [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 5488. doi:10.1158/1538-7445.AM2014-5488
miR-409-3p/-5p Promotes Tumorigenesis, Epithelial-to-Mesenchymal Transition, and Bone Metastasis of Human Prostate Cancer
Authors: Sajni Josson, Murali Gururajan, Peizhen Hu, Chen Shao, Gina Chia-Yi Chu, Haiyen E. Zhau, Chunyan Liu, Kaiqin Lao, Chia-Lun Lu, Yi-Tsung Lu, Jake Lichterman, Srinivas Nandana, Quanlin Li, Andre Rogatko, Dror Berel, Edwin M. Posadas, Ladan Fazli, Dhruv Sareen, Leland W.K. Chung
Journal: Clinical Cancer Research (2014)

miR-409-3p/-5p is a miRNA expressed by embryonic stem cells, and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines; therefore, we defined the biologic impact of manipulation of miR-409-3p/-5p on prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens.miRNA profiling of a prostate cancer bone metastatic epithelial-to-mesenchymal transition (EMT) cell line model was performed. A Gleason score human tissue array was probed for validation of specific miRNAs. In addition, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, EMT, and bone metastasis in mouse models.Elevated expression of miR-409-3p/-5p was observed in bone metastatic prostate cancer cell lines and human prostate cancer tissues with higher Gleason scores. Elevated miR-409-3p expression levels correlated with progression-free survival of patients with prostate cancer. Orthotopic delivery of miR-409-3p/-5p in the murine prostate gland induced tumors where the tumors expressed EMT and stemness markers. Intracardiac inoculation (to mimic systemic dissemination) of miR-409-5p inhibitor-treated bone metastatic ARCaPM prostate cancer cells in mice led to decreased bone metastasis and increased survival compared with control vehicle-treated cells.miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding bears particular translational importance as miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bone metastatic prostate cancer.
Treatment of Medical Officers of Unions
Authors: W. H. Parsley
Journal: BMJ (1843)

71of opium, yet " he was decidedly of opinion that the child's death was caused by opium."Dr. Babington also thought the remedy, not the disease, produced death.He tells us the heart disease arose from "a difficulty of propelling blood," but does not say how he knows that the enlargement of the heart was not congenital.It should not become fashionable to punish one mani upoIi the speculative opinions and theories of other men.We suppose tliat, generally speaking, when there are doubts, the accused party will have the benefit of them; but, as far as I am able to judge from experience, this verdict was given against the party accused, under false im- pressions, not upon facts.Anid if the judgment of the medical men of England were takeni by vote, whe- ther the evidence givell at that inquest or these remnarks and opinions are thc most reasonable, I should not fear the result.Remaining, Gentlemen,
Improvement of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C
Authors: Michael R. Kraus, Arne Schäfer, Gerlinde Teuber, Heiner Porst, Kathrin Sprinzl, Sven Wollschläger, Christian Keicher, Michael Scheurlen
Journal: Hepatology (2013)

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders.Successful eradication of HCV leads to a significant improvement of relevant aspects of attentional and neurocognitive performance, indicating that the neurocognitive impairment caused by chronic HCV infection is potentially reversible. This therefore suggests an added therapeutic benefit of antiviral treatment in HCV infection. Improvement of neurocognitive function may be an additional treatment indication in patients with HCV. (HEPATOLOGY 2013;58:497-504).
A CASE OF AURICULAR FLUTTER WITH PAROXYSMAL ATTACKS OF 1:1 CONDUCTION
Authors: R. W. SCOTT
Journal: JAMA (1922)

The appearance of a 1:1 mechanism, i. e., the ventricle beating at the same rate as the auricle, is uncommon in patients with auricular flutter. Usually there is some degree of block at the junctional tissues which determines the rate of the ventricular response. However, under some circumstances not at present clearly understood, conduction through the auriculoventricular bundle is raised, and every auricular contraction spreads to the ventricle, causing it to beat at a rate seldom seen in any other condition in man. For example, in the case here recorded the rate during attacks was 272 a minute, as determined from electrocardiographic records. Similar elevations in ventricular rate have been recorded in children by Lewis<sup>1</sup>and by Koplik,<sup>2</sup>and in adults by Mackenzie,<sup>3</sup>by White and Stevens,<sup>4</sup>and by Blackford and Willius.<sup>5</sup> <h3>REPORT OF CASE</h3> V. R., a man, aged 25, a mechanical engineer, first
Pancreaticoduodenal secretions and the genesis of gastric stump carcinoma in the rat.
Authors: R C Mason, P R Taylor, M I Filipe, I McColl
Journal: Gut (1988)

This study was designed to investigate the role of duodenogastric reflux in the genesis of gastric stump carcinoma in the rat. Carcinoma was not detected in any of the 11 control animals and in only one animal with a Roux diversion. In contrast seven of 12 animals with duodenogastric reflux developed carcinoma (p less than 0.01 and p less than 0.05 respectively). In order to determine which fraction of the reflux was implicated in the malignant process, animals with reflux of bile alone or pancreaticoduodenal secretions alone were studied. No carcinomas were found in 11 animals with bile reflux alone, but carcinoma was detected in 10 of 14 animals with reflux of pancreaticoduodenal secretions (p less than 0.01). The findings confirm that duodenogastric reflux is an important factor in the malignant process, and imply that the pancreaticoduodenal component, not bile is responsible.
Manual of Hemostasis and Thrombosis
Authors: Mehdi Tavassoli
Journal: JAMA (1983)

This manual, now in its third edition, takes a pathophysiological approach to the diagnosis and treatment of patients with bleeding and thrombotic disorders. The book is arranged in three sections. The first section describes the mechanisms involved in hemostasis and thrombosis and provides the framework for the other two sections. The role of endothelium, platelets, coagulation, and fibrinolysis are separately considered, and a brief discussion is devoted to the integration of these mechanisms in the formation and resolution of the clot. In light of these mechanisms, the other two sections offer a relevant discussion of clinical aspects of bleeding and thrombotic disorders. Two useful appendices dealing with laboratory tests for hemostasis, thrombosis, and blood component therapy conclude the manual. Major recent advances in the subject, such as the role of prostaglandins and proteases, are discussed. Recent knowledge concerning the structure of factor VIII-von Willebrand's factor, the earlier contact factors, fibrinolytic
CORRELATION OF RIGHT VENTRICULAR EJECTION FRACTION AND TRICUSPID ANNULAR PLANE SYSTOLIC EXCURSION BY ELECTROCARDIOGRAM-GATED 320 SLICE CT IN PULMONARY HYPERTENSION
Authors: Toshihiko Sugiura, Nobuhiro Tanabe, Naoko Kawata, Yukiko Matsuura, Hiroyuki Yanagawa, Ayumi Sekine, Takayuki Juzyo, Rintaro Nishimura, Miyako Saito Kitazono, Masae Uehara, Yasunori Kasahara, Nobusada Funabashi, Koichiro Tatsumi
Journal: Journal of the American College of Cardiology (2011)
Revascularization: Reflections of a Clinician
Authors: Thomas J Ryan
Journal: Journal of the American College of Cardiology (1998)

In this supplement to the Journal of the American College of Cardiology , we are treated to a superb recount of the history, birth, growth and development of coronary revascularization as it exists today in the form of coronary artery bypass graft surgery (CABG) and percutaneous transluminal
ENCEPHALITOZOON CUNICULI AS A KIDNEY PARASITE IN THE RABBIT
Authors: Theobald Smith, Laura Florence
Journal: The Journal of Experimental Medicine (1925)

A spontaneous epidemic of nephritis among young rabbits associated with a protozoan parasite has been observed in a certain breeding stock since 1918. It is regarded as a nest infection. The parasite is tentatively classed among the microsporidia and the stages encountered are regarded as vegetative which may perhaps pass through several generations in the same host. It is a parasite of the epithelial cell, provoking no immediate host reactions. These are supposed to follow injury such as destruction of the epithelium and denudation and plugging of the tubules. The localizations in the brain are also without cell reaction, except under special conditions, and the many cell foci present are attributed to coccidia and perhaps bacteria and other intestinal parasites. The kidneys are looked upon as the normal habitat and the brain parasites as aberrant and outside the normal cycle unless it can be shown that the spores discharged into the circulation may again multiply in some organ like the kidneys in direct communication with the exterior. It is highly probable that many reported cases of nephritis among older rabbits used in experiments had their origin in an early invasion of the parasite described.
Mechanism of Factor X Deficiency in Systemic Amyloidosis
Authors: Bruce Furie, LiAnn Voo, Keith P. W. J. McAdam, Barbara C. Furie
Journal: New England Journal of Medicine (1981)

SOME patients with primary (immunoglobulintype) amyloidosis acquire a coagulation disorder characterized by factor X deficiency1 2 3 4 5 6 7 8 9 10 11 12 13 and occasionally factor IX deficiency.12 , 13 These patients may have hemorrhagic complications superimposed on the clinical manifestations of amyloidosis. We have previously demonstrated that the acquired factor X deficiency in this disorder is due to rapid clearance of factor X from the circulating blood, with immobilization of the protein in the vasculature.11 This observation explains why these patients are refractory to replacement therapy involving infusion of plasma and plasma fractions containing factor X. The direct binding of factor X to amyloid fibrils exposed to circulating blood . . .
Pelvic-Organ Prolapse and Uterine Inversion
Authors: Christl Reisenauer, Erich Solomayer
Journal: New England Journal of Medicine (2009)

A 68-year-old woman presented with dull, persistent abdominal pain, the sensation of a foreign body in the pelvis, difficulty voiding, and vaginal discharge. The symptoms had developed over many years, after two uncomplicated, spontaneous deliveries; at the time of presentation, the symptoms had become unbearable. Physical examination revealed a normal abdomen without a mass; on external inspection of the vulva, the pelvic organs were visibly prolapsed. The prolapsed structure, 30 cm in length, consisted of the vagina (arrow) and the inverted endometrium (asterisk). Repositioning was successfully performed manually in the clinic. The patient underwent vaginal hysterectomy and surgical repair of . . .
Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection
Authors: Andy L Johnson, L Aravind, Natalia Shulzhenko, Andre Morgun, See-Young Choi, Tanya L Crockford, Teresa Lambe, Heather Domaschenz, Edyta M Kucharska, Lixin Zheng, Carola G Vinuesa, Michael J Lenardo, Christopher C Goodnow, Richard J Cornall, Ronald H Schwartz
Journal: Nature Immunology (2009)
The Myocardial Infarction Rehabilitation Center
Authors: Howell F. Wright
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The Heart Disease Advisory Committee's article, "Optimal Criteria for Care of Heart Disease Patients" (226:1340, 1973) disappointed me because within their hospital categories no mention was made of the long-term care of heart disease patients. Now is the time for more hospitals to go one step further and establish postmyocardial infarction exercise rehabilitation centers. The value of early ambulation and progressive exercise programs to the cardiac patient is being more favorably documented each day. Publications on this topic, however, point to exercise environment controls that must be maintained if additional catastrophes are to be prevented. Where can a physician and his patient find this controlled environment? Possibly a YMCA, recreation center, or nearby university has a specialized adult fitness program. Unfortunately, these programs, when found, often lack experienced professional personnel and emergency equipment. The addition of a physical educator to a hospital staff would complete the team