tbuckley/cabot-search huggingface dataset:
Importance of Idiopathic Pulmonary Fibrosis Staging for Clinical Trial Endpoints
Authors: Oisin J. O’Connell, Peter Riddell, Jim J. Egan
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

We welcome the Pulmonary Perspective on the evaluation of clinically meaningful primary endpoints for idiopathic pulmonary fibrosis (IPF) (1). However, the logic of this discussion is weakened by the failure to acknowledge that the disease progression is influenced by the burden of disease at presentation. The burden of disease is normally described by a staging system, which is currently absent for IPF. One specific endpoint will clearly be insufficient if applied to “all comers with IPF.” Therefore, the definition of endpoints is heavily dependent on the staging of the disease (2). Regrettably, we have not seen a formal staging system emerge from the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guideline publication (3). We have learned from randomized controlled studies that change in FVC is a very pragmatic endpoint to be applied in patients with “mild to moderate disease,” which equates with a limited burden of disease. In patients with limited disease, defined as a gas transfer of greater than 40% predicted (2), mortality as an endpoint has a very low frequency. In contrast, mortality as an endpoint is more common in patients with advanced disease, defined as a gas transfer less than 40%. Therefore the relative endpoints are dependent on the stage of the disease. This burden/stage of disease can be defined on the basis of simple lung function testing. We would encourage the debate to consider that the appropriate endpoints should be defined on the basis of the burden or stage of disease, and that the discussions highlight the need for a simple reproducible staging system for IPF in a manner comparable to the Global Initiative for Chronic Obstructive Lung Disease classification for chronic obstructive pulmonary disease.
Outcome of Lung Cancer Patients Requiring Mechanical Ventilation for Pulmonary Failure
Authors: Michael S. Ewer, M. K. Ali, Mohamed S. Atta, Rodolfo C. Morice, P. V. Balakrishnan
Journal: JAMA (1986)

The prognosis of lung cancer patients who are not candidates for surgery is usually poor. The unfavorable natural history of respiratory failure in this group of patients has been suggested as a causative factor. We analyzed the outcome of 46 consecutive patients with primary lung cancer on whom mechanical ventilators were utilized. Although seven patients were ultimately weaned and survived for at least 24 hours, three of them subsequently died prior to discharge from the hospital. The remaining 39 patients died while using the ventilator. Patient age, tumor cell type, and the etiology of respiratory failure were not significantly different between the weaned and unweaned populations. A difference was noted in the duration of mechanical ventilation: none of the patients who could be weaned required mechanical ventilation for more than six days (range, two to six days). Respiratory failure in the nonsurgical lung cancer patient carries a poor prognosis, and selection of patients for mechanical ventilation should be conservative.
Cytoplasmic Tubular Structures in Liver of HBsAg Carrier Chimpanzees Infected with Delta Agent and Comparison with Cytoplasmic Structures in Non-A, Non-B Hepatitis
Authors: Tomoteru Kamimura, Antonio Ponzetto, Ferruccio Bonino, Stephen M. Feinstone, John L. Gerin, Robert H. Purcell
Journal: Hepatology (2007)

Electron microscopic observations were carried out on five HBsAg carrier chimpanzees infected with delta (δ) agent and two chimpanzees infected with human non-A, non-B hepatitis. The cytoplasmic tubular structures, which have been recognized in the liver of chimpanzees infected with human non-A, non-B hepatitis, were found also in the liver of HBsAg carrier chimpanzees infected with 5 agent. The quantity of the cytoplasmic structures in serial studies was associated with SGPT elevation rather than with expression of ± antigen in sera and liver tissues. This indicates that the cytoplasmic structures reflect a pathologic change of the hepatocytes in chimpanzees infected with ± agent or human non-A, non-B hepatitis. These and other similarities between the two agents suggest a similar nature.
The Runaway American Health Care System
Authors: Jack Rodnick
Journal: JAMA (1990)

<h3>To the Editor.—</h3> There is no doubt that the American medical care system has major problems. Many of these are well documented in the recent communication by Drs Davies and Felder.<sup>1</sup>I believe that one of the factors that is closely related to the problems they reviewed was not mentioned in the article. This factor is the lack of primary care physicians in the United States. The United States not only spends more money per capita for medical care than any other westernized country, we also have a smaller percent of our physicians in primary care.<sup>2</sup>Health maintenance organizations, which have lower costs per enrollee than indemnity plans, average 51.4% primary care physicians (family practice, pediatrics, and general internal medicine).<sup>3</sup>This percentage is far greater than the estimated 27% of American physicians who currently function as generalists.<sup>4</sup>Primary care physicians who provide coordinated, comprehensive, and continuous
Hepatic glucose sensing: does flux matter?
Authors: Masakazu Shiota, Mark A. Magnuson
Journal: Journal of Clinical Investigation (2008)

In this issue of the JCI, Denechaud et al. report studies investigating the role of the liver X receptors (LXRs) LXRalpha and LXRbeta in carbohydrate sensing by the liver (see the related article beginning on page 956). The results of this study, which utilized LXRalpha/beta double-KO mice, strongly contradict a recent Nature report that proposed that LXRalpha/beta sense glucose independent of metabolic flux. The reported findings further support a key role for the carbohydrate-responsive element-binding protein (ChREBP) in the regulation of lipogenic genes by glucose and dietary carbohydrates.
SOME NEWER CONCEPTIONS OF URINARY STONE FORMATION
Authors: DELLINGER BARNEY
Journal: JAMA (1934)

This communication concerns itself primarily with a discussion of hyperparathyroidism as a cause of urinary calculi. In the course of our remarks, certain other possible etiologic factors will be dealt with. Next perhaps to malignant disease, urinary lithiasis presents one of the most difficult problems confronting the urologist. Until this question is answered he finds himself occupied in the more or less unproductive occupation of discovering and removing stones from the kidney, ureter or bladder. We do not hesitate to say that no hypothesis as to etiology yet presented can be defended from every line of attack, nor does it matter that certain experimental studies have resulted in stone formation. What may be true in the laboratory does not necessarily follow in the clinic. Even parathyroid disease, which is found to be the apparent etiologic factor in at least 10 per cent of cases, brings up questions that in the
UK has fifth highest rate of type 1 diabetes in children, new figures show
Authors: G. Iacobucci
Journal: BMJ (2013)

The United Kingdom ranks fifth of 88 countries in the incidence of type 1 diabetes in children, a new analysis has shown.

A league table compiled by the charity Diabetes UK from data from the International Diabetes Federation shows that each year 24.5 in every 100 000 children aged up to 14 years are given a diagnosis. Only Finland, Sweden, Saudi Arabia, and Norway have a higher incidence.⇓

View this table:

Top 10 countries by incidence of type 1 diabetes in children aged up to 14 years



The UK rate was more than double that of France …
Abstract LB-304: ATSP-9172, a novel Stapled Peptide inhibitor of HIF-dependent transcriptional activity with <i>in vivo</i> antitumor efficacy in a preclinical model of prostate cancer.
Authors: Kaiming Sun, Steven J. DeMarco, Vincent Guerlavais, Aditi Mukherjee, Sean Irwin, Eric Shi, Hongliang Cai, Krzysztof Darlak, Solimar Santiago, Jessica Pero, Karen A. Olson, Huw M. Nash, Yong Chang
Journal: Cancer Research (2013)

Abstract Hypoxia-inducible transcription factors (HIF) are key regulators of cellular adaptation to hypoxia in solid tumors, and HIF-1α controls the expression of genes involved in anaerobic metabolism, angiogenesis, cell growth and survival. Hydrocarbon cross-linked alpha helical peptides (Stapled Peptides) are a breakthrough approach to create new class of drugs that modulate intracellular protein-protein interactions. Here, we have mimicked the structure and function of the CITED2 protein, an endogenous negative regulator of the interaction between HIF-1α and p300 proteins, by designing a Stapled Peptide derived from CITED2 to generate the first example of a potent and selective Stapled Peptide inhibitor of HIF-1α-dependent transcription. ATSP-9172 bound to the CH1 domain of p300 and disrupted the HIF-1α C-TAD/CH1 interaction in biochemical assays and inhibited HIF-dependent reporter gene activity in ME-180 cells. Examination of endogenous transcript levels in ME-180 cells revealed that ATSP-9172 down-regulated the transcription of HIF-1α target genes, such as adolase C, angiopoietin-like 4, and carbonic anhydrase 9 in a dose-dependent manner, but did not affect the expression of non-HIF target genes, verifying a specific and on-target mechanism of action. ATSP-9172 exhibited a dramatic improvement in solubility and plasma stability profile relative to the linear peptide, and demonstrated favorable pharmacokinetic properties in mice by providing high systemic exposure, low plasma clearance and long elimination half-life. Finally, intravenous administration of ATSP-9172 on an every other day schedule significantly inhibited tumor growth in a PC-3 human prostate tumor xenograft model (p &amp;lt; 0.05); this inhibition was found to be dose-dependent. Our results demonstrate that a Stapled Peptide mimicking the HIF inhibitory function of the native CITED2 protein provides a novel and specific strategy to suppress HIF-1α-dependent gene expression for cancer therapy. Citation Format: Kaiming Sun, Steven J. DeMarco, Vincent Guerlavais, Aditi Mukherjee, Sean Irwin, Eric Shi, Hongliang Cai, Krzysztof Darlak, Solimar Santiago, Jessica Pero, Karen A. Olson, Huw M. Nash, Yong Chang. ATSP-9172, a novel Stapled Peptide inhibitor of HIF-dependent transcriptional activity with in vivo antitumor efficacy in a preclinical model of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-304. doi:10.1158/1538-7445.AM2013-LB-304
Yoga for bronchial asthma: a controlled study.
Authors: R Nagarathna, H R Nagendra
Journal: BMJ (1985)

Fifty three patients with asthma underwent training for two weeks in an integrated set of yoga exercises, including breathing exercises, suryanamaskar, yogasana (physical postures), pranayama (breath slowing techniques), dhyana (meditation), and a devotional session, and were told to practise these exercises for 65 minutes daily. They were then compared with a control group of 53 patients with asthma matched for age, sex, and type and severity of asthma, who continued to take their usual drugs. There was a significantly greater improvement in the group who practised yoga in the weekly number of attacks of asthma, scores for drug treatment, and peak flow rate. This study shows the efficacy of yoga in the long term management of bronchial asthma, but the physiological basis for this beneficial effect needs to be examined in more detail.
Psychophysiological Study on Fasting Therapy
Authors: Haruyoshi Yamamoto, Jinichi Suzuki, Yuichi Yamauchi
Journal: Psychotherapy and Psychosomatics (1979)

The Tohoku University method of fasting therapy was performed on 380 patients. The clinical results revealed an efficacy rate of 87%. With regard to psychosomatic diseases, irritable colon syndrome, neurocirculatory asthenia, mild diabetes mellitus, obesity and borderline hypertension were good indications for this therapy. In order to clarify the therapeutic mechanism, several clinical examinations were administered before, during and after therapy. EEG data was analysed according to the power spectral method. The peak frequency decreased as fasting progressed, while it increased as re-fed continued. Percent energy of alpha waves after fasting therapy was significantly higher than that of the pre-fasting stage. The dexamethasone suppression rate of urine 17-OHCS after fasting therapy was significantly lower than that of the pre-fasting stage. It seems that ketone nutrition may work as a strong stressor in the brain cell, temporarily placing all biological mechanisms in a stress state and then activating the natural healing power inherent to the human body, thereby bringing about homeostasis.
Phase I dose-escalation (DE) trial of high-dose melphalan (M) with palifermin (P) for cytoprotection followed by autologous stem cell transplantation (ASCT) for myeloma (MM) patients with abnormal renal function (AbRF).
Authors: N. Tageja, Z. S. Al-Kadhimi, S. Cronin, J. Abrams, M. Ventimiglia, L. G. Lum, L. J. Ayash, V. Ratanatharathorn, J. P. Uberti, M. H. Abidi
Journal: Journal of Clinical Oncology (2010)

e18560 Background: Melphalan (M) is the most effective conditioning agent for MM patients (pts) undergoing ASCT. M pharmacokinetics (PK) are not adversely affected by AbRF. Despite its steep, log-linear dose effect, M 140 mg/m2 is the standard conditioning regimen in pts with AbRF because of pronounced toxicity of M > 200 mg/m2. In a retrospective review, (Grazziutti et al) concluded that BSA based dosing of M results in wide variations in the mg/kg dose. Pts with AbRF, treated with high mg/kg M dose have the greatest risk for severe oral mucositis (OM) following ASCT. P as a cytoprotective agent has demonstrated efficacy in reducing intensity and duration of OM in pts receiving intensive chemo-radiotherapy. In an effort to DE M, we designed this study to determine the MTD of M in pts stratified based on AbRF (CrCl <60) when used with P to decrease the duration and severity of OM. Methods: Since July 2007, 14 pts have been enrolled. Eligibility criteria included age 18-74 years, stage 2/3, ECOG PS ≤ 2, no dialysis, no active OM and suitable for ASCT. DE proceeded (3 pts cohorts) depending on the dose limiting toxicities (DLT). Level 1 began at M 140 mg/m2 (D-2) with P 60 mcg/kg/d, given as I.V. bolus on Day -5,-4, - 3 & Day +1, +2 and +3 (PBSCs infused on Day 0). Subsequent DE were done at 20 mg/m2 increments up to M 220 mg/m2. If no symptomatic grade ≥3 DLTs were noted by day +30, an additional cohort of 3 pts were entered at the next dose level. DE were to stop if ≥2 DLTs occurred at M dose; with that dose declared as the MTD. Grade 3/ 4 diarrhea and ≥ grade 3 cardiac toxicity was considered DLT; grade 3/ 4 hematological toxicity was acceptable. The grade of OM was assessed daily according to WHO oral toxicity scale (grade 0 to 4).The pts reported questionnaire evaluating overall health, mouth and throat soreness (MTS) was administered from Day -5 to + 28. Results: This trial is still recruiting pts. M was given in doses up to and including 200 mg/m2 (n=2). Based on the DLT we would need minimum of 4 or maximum 7 pts to complete this study. Conclusions: P may permit safe DE of M, thus reaching or exceeding the M dose 200 mg/m2 used for MM patients with normal renal function. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biovitrium
Authors' reply to Harding and colleagues, Taylor, Cruickshank, and El Turabi and Payne
Authors: B. Williams, T. Krause, K. Lovibond, M. Caulfield, T. McCormack
Journal: BMJ (2011)

We agree with Harding and colleagues that special consideration should be given to prescribing antihypertensive treatment to women of childbearing potential.1 The important guidance they cite is included in all of the guideline outputs from the National Institute for Health and Clinical Excellence (NICE).

In reply to Taylor,2 we considered all data on the prognostic value of ambulatory blood pressure monitoring (APBM) compared with clinic blood pressure and home blood pressure monitoring and found that as APBM best predicted clinical outcomes …
Effects of aging and long term dietary intervention on protein turnover and growth of ventricular muscle in the rat heart
Authors: D. F GOLDSPINK, S. E M LEWIS, B. J MERRY
Journal: Cardiovascular Research (1986)

The developmental growth of the combined right and left ventricles was followed from weaning to senility in rats receiving an unrestricted diet (controls) or pair fed to one half of this food intake. The normal developmental increases in the ventricular weight, protein mass, and nucleic acid contents were retarded by this long term dietary regimen. Although the same maximum values for each variable were ultimately reached in the ventricles of the calorie restricted animals, these were achieved approximately one year later (that is, well into the extended lifespan afforded by such underfeeding). This nutritional slowing of cardiac growth was explained by a retarding of the normal developmental decline in the fractional rates of protein synthesis and protein breakdown (measured in vivo). In the control animals a net loss of ventricular protein occurred over the second year, and this might possibly be associated with a decrease in the mechanical efficiency of the aging heart. Although a similar aging atrophy was found in the ventricles of the diet restricted rats, it was delayed by a year and may be an important factor contributing to the increased longevity. This dietary intervention appears to slow the normal age related changes in cardiac protein turnover.
Nicolo Paganini
Authors: Myron R. Schoenfeld
Journal: JAMA (1978)

The thesis is advanced that Nicolo Paganini of Genoa (1782 to 1840), the greatest violin virtuoso of all time, owed his incomparable violin virtuosity to a fortuitous and fortunate coincidence of three factors: a soaring musical genius, a flair for the dramatic and ostentatious, and manual dexterity conferred by being born with the long fingers and hyperextensible joints of Marfan's syndrome. Ordinarily, an inborn connective tissue disorder is a calamity for the patient and a burden for society. In this particular instance, however, Marfan's syndrome bequeathed to posterity a legacy that will ennoble the human spirit for innumerable generations yet to come. (<i>JAMA</i>239:40-42, 1978)
Anabolic Steroids and Sports-Reply
Authors: Virginia S. Cowart
Journal: JAMA (1987)

<h3>In Reply.—</h3> Texas has followed the lead of California, Ohio, and Alabama in passing legislation to control anabolic steroid use. It will be interesting to see how well the legislation can be enforced. Sources have told us that it takes as little as a week to reestablish black market trade in steroids after a disruption such as an arrest. Meanwhile, the federal government is making a strong push for control through its cooperative task force. I do agree that young athletes in some states—like Texas— are especially vulnerable to steroid use because of the statewide emphasis on sports and that those states may need to look at control in a different light.
Cardiac Allotransplantation in Newborns as Therapy for Hypoplastic Left Heart Syndrome
Authors: Leonard L. Bailey, Sandra L. Nehlsen-Cannarella, Robin W. Doroshow, John G. Jacobson, Robert D. Martin, Martin W. Allard, Manly R. Hyde, Rose H. Dang Bui, Eugene L. Petry
Journal: New England Journal of Medicine (1986)

Hypoplastic left heart syndrome constitutes a spectrum of severe congenital cardiovascular anomalies dominated by underdevelopment or absence of the left ventricle, aortic valve, and mitral valve. The ascending and arch segments of aorta are usually of very small caliber, and a diaphragm-like segment of aortic coarctation typically occupies what should be the preductal aortic isthmus. The ductus arteriosus empties directly into a descending thoracic aorta of normal caliber. The surgical morphologic nature of this complex syndrome has been clearly described.1 2 3 4 These developmental malformations are a prelude to fatal postnatal pathophysiologic processes. Survival after birth depends entirely on adequate systemic blood . . .
The Practice of Cardiology
Authors: Arthur J. Moss
Journal: JAMA (1981)

Clinical cardiology has undergone dramatic changes in the past decade, and a text that deals with the current state of the science and art of cardiology is long overdue.<i>The Practice of Cardiology</i>is a highly readable, clinically oriented series of 42 essays by 52 contributors (cardiologists, thoracic surgeons, anesthesiologists, and psychiatrists) from the Massachusetts General Hospital. The three editors have organized the book into nine sections that cover four major areas: syndromes common to cardiac disease in general, specific cardiac diseases, diagnostic techniques, and the perioperative care of the cardiac patient. Each chapter begins with a brief outline of the major topics to be covered and concludes with a pertinent list of references in alphabetic order by first author. The numerous illustrations are generally of good quality. The authors and editors are to be congratulated for emphasizing and highlighting the clinical judgment and decision-making process that the experienced physician
A Case of Nonischemic T-Wave Inversions
Authors: Lindee Strizich Tull, Zachary D. Goldberger
Journal: JAMA Internal Medicine (2014)

Aman in his 30swith amedical history of remote pulmonary embolus (PE) and antiphosholipid antibody (APLA) syndrome presented to theemergencydepartmentwithprogressivedyspneaon exertion of 3 months’ duration. He also reported subacute, occasional, dull, substernal and right-sided exertional chest pain and a 10-pound unintentional weight loss. His temperature was 36.4°C; heart rate,60bpm;bloodpressure, 117/82mmHg; respirations, 18/ min; and resting oxygen saturation, 98%on ambient air. However, hisoxygensaturationdecreased to82%withambulation.Theother findingsofhisphysicalexaminationwere largelyunremarkable,other thanwidened splitting of S2. The laboratory evaluations, including cardiac troponin levels, were unremarkable. The initial electrocardiogram (ECG) is shown in the Figure. Question: Should this patient be taken for emergency coronary angiography?
Uses of Nomenclature
Authors: Carl G. Madsen
Journal: JAMA (1975)

<h3>To the Editor.—</h3> I'm writing to say how much I enjoyed the book review (231:982, 1975) in which Marjorie C. Meehan, MD, reviewed<i>Models of Madness, Models of Medicine</i>by Miriam Siegler and Humphrey Osmond (Macmillan, 1974). I agree that in our clinical effort to get at the causes of aberrant behavior and function, clinicians have generated nomenclature expressing that same predominately causal focus so succinctly expressed by Dr Meehan. Unfortunately, when third parties have preoccupied themselves with generating categories of individuals regarded as deserving of funds, they have borrowed from clinical nomenclature and established categorical funding according to etiologic categories. In the state of Ohio, accusations of misappropriation of funds may be made if mental retardation funds go for the operation of mental health agencies. Champions of each category jealously guard funds from dispersal to agencies caring for individuals similarly incapacitated and functionally capable of benefiting from programs of
The HBS1L-MYB intergenic interval associated with elevated HbF levels shows characteristics of a distal regulatory region in erythroid cells
Authors: Karin Wahlberg, Jie Jiang, Helen Rooks, Kiran Jawaid, Fumihiko Matsuda, Masao Yamaguchi, Mark Lathrop, Swee Lay Thein, Steve Best
Journal: Blood (2009)