tbuckley/cabot-search huggingface dataset:
A Shortage of Reliable Data
Authors: Thomas C. Chalmers
Journal: New England Journal of Medicine (1976)

As the art of therapy is slowly transformed into the science of therapeutics, treatment of the individual patient can be expected to be a source of considerable confusion. A growing list of problems includes the use of antibiotics for infections not caused by specifically identified and susceptible organisms, the multiple agents now available for managing hypertension, the use of oral hypoglycemic drugs in diabetes, of lipid lowering, vasodilating, anticoagulant and antiplatelet agents in coronary-artery disease, and many other drugs designed to correct various acute and chronic disorders. The confusion arises in part from the fact that many drugs have been . . .
High dose steroid bolus given for occlusion of central retinal artery.
Authors: J. C. Pandit, F. Tiamiyu
Journal: BMJ (1992)

overlap with the groupings of HbAI concentration at seven years.At three months into the study patients with strict diabetic control showed a worsening of retinopathy relative to those receiving more casual treatment.2At two years strict control seemed to be of benefit,' but the small difference had disappeared at 3 5 years.4The present report at seven years is claimed to argue for a benefit of strict control (as judged by HbA1 concentration), but the results are clearly equivocal and do not answer the question of whether a strict insulin regimen (which carries its own risks5) is ofbenefit.
How to Decide Whether a Clinical Practice Guideline Is Trustworthy
Authors: David F. Ransohoff, Michael Pignone, Harold C. Sox
Journal: JAMA (2013)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
32P-Sodium Phosphate Treatment of Metastatic Malignant Disease
Authors: DOUGLAS JAMES ROBERTS
Journal: Clinical Nuclear Medicine (1979)

Thirty-four patients with cancer of the breast and 12 with cancer of the prostate were treated with testosterone and32P-sodium phosphate for relief of pain from bony metastases. Thirty received chemotherapy as well, and 34 received external radiation to single ports for localized pain. Of the 46 patients, 34 had good results, 6 fair, and 6 were failures. Ten patients needed transfusion for marrow depression; no other side effect was observed.
Toxicant-induced loss of tolerance--an emerging theory of disease?
Authors: C S Miller
Journal: Environmental Health Perspectives (1997)

This paper attempts to clarify the nature of chemical sensitivity by proposing a theory of disease that unites the disparate clinical observations associated with the condition. Sensitivity to chemicals appears to be the consequence of a two-step process: loss of tolerance in susceptible persons following exposure to various toxicants, and subsequent triggering of symptoms by extremely small quantities of previously tolerated chemicals, drugs, foods, and food and drug combinations including caffeine and alcohol. Although chemical sensitivity may be the consequence of this process, a term that may more clearly describe the observed process is toxicant-induced loss of tolerance. Features of this yet-to-be-proven mechanism or theory of disease that affect the design of human exposure studies include the stimulatory and withdrawallike nature (resembling addiction) of symptoms reported by patients and masking. Masking, which may blunt or eliminate responses to chemical challenges, appears to have several components: apposition, which is the overlapping of the effects of closely timed exposures, acclimatization or habituation, and addiction. A number of human challenge studies in this area have concluded that there is no physiological basis for chemical sensitivity. However, these studies have failed to address the role of masking. To ensure reliable and reproducible responses to challenges, future studies in which subjects are evaluated in an environmental medical unit, a hospital-based facility in which background chemical exposures are reduced to the lowest levels practicable, may be necessary. A set of postulates is offered to determine whether there is a causal relationship between low-level chemical exposures and symptoms using an environmental medical unit.
Adjuvant Chemoradiation for Pancreatic Cancer: Few Good Data, Much Debate
Authors: Renee Twombly
Journal: JNCI Journal of the National Cancer Institute (2008)

What everyone agrees on is that adenocarcinoma of the pancreas is formidable. Five-year survival in patients given so-called curative surgery hovers between 10% and 20%. And only 10% – 15% of patients are even eligible for surgery by the time they are diagnosed. It is a relatively uncommon cancer, but annual mortality ( ~ 34,000 deaths) approximates annual incidence ( ~ 37,000 cases). It is the fourth-leading cause of cancer-related death for both men and women in the U.S. Fewer than 5% of all patients diagnosed with pancreatic cancer are expected to live 5 years after diagnosis, and no treatment strategy, including targeted therapies, appears to offer much hope. “Rather than fi ght about whether to use radiation or not, we should all come together to fi gure out how to integrate as many therapies as possible to treat our patients better,” said radiation oncologist Joseph Herman , M.D., of Johns Hopkins Kimmel Cancer Center in Baltimore.
p73β-Mediated Apoptosis Requires p57kip2 Induction and IEX-1 Inhibition
Authors: Susana Gonzalez, Manuel M. Perez-Perez, Eva Hernando, Manuel Serrano, Carlos Cordon-Cardo
Journal: Cancer Research (2005)

Abstract Similarly to p53, p73α and p73β induce growth arrest and/or apoptosis in response to DNA damage or when exogenously expressed. However, how they trigger apoptosis remains unresolved. After stable transduction of either p73α or p73β, a greater apoptotic response was observed for p73β in both primary and tumor cells. Consistently, blocking ectopic and endogenous p73β expression by specific shRNA significantly decreased apoptotic levels after DNA damage. We found that p73β targets the apoptotic program at multiple levels: (i) facilitating caspase activation through p53-dependent signals and (ii) inducing p57KIP2, while down-regulating c-IPA1 and IEX1 through a p53-independent mechanism. p73β-mediated apoptosis was considerably reduced after inhibition of p57KIP2 by small interfering RNA, IEX-1 overexpression, and in mouse embryo fibroblasts derived from p57−/− mice. Data from this study offer evidence for the apoptotic activity exclusive of p73β. In the clinical context, these results might have potential therapeutic implications, because p73β could induce alternative apoptotic responses in tumors harboring p53 mutations.
US thyroid cancer rates are epidemic of diagnosis not disease, study says
Authors: M. McCarthy
Journal: BMJ (2014)

The rising incidence of thyroid cancer in the United States is not an epidemic of disease but one of diagnosis, a new study claims.1

In the study Louise Davies and Gilbert Welch of the Dartmouth Institute for Health Policy and Clinical Practice in Hanover, New Hampshire, analyzed data on the incidence of thyroid cancer from the National Cancer Institute’s SEER program and data on thyroid cancer mortality from the National Vital Statistics System from 1975 to 2009.

They found that the incidence of thyroid …
Atypical Hyperlipoproteinemia and Pancreatitis.
Authors: Richard G. Farmer
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Atypical Hyperlipoproteinemia and Pancreatitis.Richard G. Farmer, M.D., F.A.C.P., Eugene I. Winkelman, M.D., F.A.C.P., Helen B. Brown, Ph.D., Lena A. Lewis, Ph.D.Richard G. Farmer, M.D., F.A.C.P.Search for more papers by this author, Eugene I. Winkelman, M.D., F.A.C.P.Search for more papers by this author, Helen B. Brown, Ph.D.Search for more papers by this author, Lena A. Lewis, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-859_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA prospective study was begun in 1969 to investigate the relationship of hyperlipidemia and pancreatitis. Ten patients were studied. All had discrete, recurrent, acute pancreatitis, with typical pain, hyperamylasemia, and hyperlipidemia during the acute phase. Six underwent laparotomy; three had cholecystectomy, but none had cholelithiasis. None were alcoholics, had chronic liver disease, hypercalcemia, or family histories of similar illnesses. Hypertriglyceridemia was present in all; rising levels correlated with abdominal pain (range, 400 to 9000 mg/100 ml; mean, 3000 mg/100 ml). Chylomicronemia was present in nine; cholesterol elevation was modest (mean, 450 mg/100 ml); and elevated prebeta lipoproteins were present in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMarked Hyperlipidemia and Pancreatitis Associated with Oral Contraceptive Therapy 1 May 1972Volume 76, Issue 5Page: 859-859KeywordsCholecystectomyCholelithiasisChronic liver diseaseHypercalcemiaHypercholesterolemiaHyperlipidemiaLaparotomyLipoproteinsPancreatitisProspective studies Issue Published: 1 May 1972 PDF downloadLoading ...
The Kinetocardiogram
Authors: E. E. EDDLEMAN, KATHRYN WILLIS, T. J. REEVES, T. R. HARRISON
Journal: Circulation (1953)

A simple method of recording low-frequency precordial movements is presented and termed kinetocardiogram to indicate movements as the result of the motions of the heart. The normal precordial patterns are described as well as the time relationships to the cardiac cycle and ballistocardiogram.
Diagnosis of Sickle Cell Anemia and β-Thalassemia with Enzymatically Amplified DNA and Nonradioactive Allele-Specific Oligonucleotide Probes
Authors: Randall K. Saiki, Chu-An Chang, Corey H. Levenson, Tina C. Warren, Corinne D. Boehm, Haig H. Kazazian, Henry A. Erlich
Journal: New England Journal of Medicine (1988)

We have developed a simple and rapid nonradioactive method for detecting genetic variation and have applied it to the diagnosis of sickle cell anemia and β-thalassemia. The procedure involves the selective amplification of a segment of the human β-globin gene with oligonucleotide primers and a thermostable DNA polymerase, followed by hybridization of the amplified DNA with allele-specific oligonucleotide probes covalently labeled with horseradish peroxidase. The hybridized probes were detected with a simple colorimetric assay. We demonstrated the usefulness of this method in a retrospective analysis of two pregnancies at risk for β-thalassemia and one at risk for sickle cell anemia, as well as in an analysis of nine DNA samples simulating three family sets. (N Engl J Med 1988; 319:537–41.)
Lack of money and poor security are barriers to global eradication of polio
Authors: A. Gulland
Journal: BMJ (2012)

The United Nations’ secretary general, Ban Ki-moon, has called on warring parties in countries where polio is endemic to ensure that healthcare workers are given safe passage to carry out vaccination programmes.

Ban, who was talking at a meeting on polio eradication at the UN general assembly in New York last week, urged all sections of the community in affected countries to come together to eradicate polio “once and for all.”

He said, “Where there is fighting and insecurity we need warring parties to allow aid workers to operate. I appeal to all parties to provide safe passage to health workers to vaccinate children.”

Ban was talking three months after a polio vaccination worker was shot and killed in Pakistan. In …
Serum lipid concentrations and blood pressure in obese women.
Authors: R G Wilcox
Journal: BMJ (1978)

In 70 obese women no correlation was found between body weight and serum cholesterol or triglyceride concentrations, but there was a significant correlation between weight and blood pressure. Weight reduction by diet or jejunoileal shunt was not accompanied by any significant change in serum lipid concentrations other than the decrease in serum cholesterol expected after intestinal bypass. Twelve months after bypass surgery was carried out on 14 patients, however, both systolic and diastolic blood pressures were significantly reduced and at levels appropriate to the patients9 new weights. These results suggest that obesity in women cannot be taken to indicate the presence of hyperlipidaemia and that sustained weight loss may lower blood pressure.
Abstract 741: Combined inhibition of MDM2 and MEK for KRAS mutant non-small cell lung cancer
Authors: Aaron N. Hata, Hannah L. Archibald, Maria D. Gomez-Caraballo, Laurent R. DeBussche, Sukhvinder Sidhu, James Watters, Jeffrey A. Engelman
Journal: Cancer Research (2014)

Abstract There are currently no effective targeted therapies for KRAS mutant NSCLC. Combination drug strategies that target downstream pathways activated by mutant KRAS are currently being investigated, however efficacy may be limited by inability to induce a sufficient apoptotic response. MDM-2 (murine double minute 2) is a ubiquitin ligase that negatively regulates p53 function by promoting its degradation. Inhibitors of the MDM2-p53 interaction lead to p53 activation and transcription of genes promoting cell cycle arrest and apoptosis. We investigated the efficacy of combined MEK and MDM2 inhibition for KRAS mutant NSCLC. In KRAS mutant NSCLC cell lines with wild-type p53, pimasertib (MEKi) and SAR405838 (MDM-2i) led to upregulation of BIM and PUMA respectively. Induction of apoptosis and cell cycle arrest correlated with in vitro efficacy, and the combination exhibited marked in vivo activity against KRAS mutant p53 wild-type NSCLC xenograft tumors. These studies provide rationale for future clinical investigation of combined MEK and MDM-2 inhibition for KRAS mutant NSCLC. Citation Format: Aaron N. Hata, Hannah L. Archibald, Maria D. Gomez-Caraballo, Laurent R. DeBussche, Sukhvinder Sidhu, James Watters, Jeffrey A. Engelman. Combined inhibition of MDM2 and MEK for KRAS mutant non-small cell lung cancer. [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 741. doi:10.1158/1538-7445.AM2014-741
Arterial Stiffness Is Independently Associated with Emphysema Severity in Patients with Chronic Obstructive Pulmonary Disease
Authors: David A. McAllister, John D. Maclay, Nicholas L. Mills, Grant Mair, Joy Miller, David Anderson, David E. Newby, John T. Murchison, William MacNee
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

More patients with chronic obstructive pulmonary disease (COPD) die of cardiovascular causes than of respiratory causes, and patients with COPD have increased morbidity and mortality from stroke and coronary heart disease. Arterial stiffness independently predicts cardiovascular risk, is associated with atheromatous plaque burden, and is increased in patients with COPD compared with control subjects matched for cardiovascular risk factors. Elastin fragmentation and changes in collagen are found in the connective tissue of both emphysematous lungs and stiff arteries, but it is not known whether the severity of arterial stiffness in patients with COPD is associated with the severity of emphysema.To identify whether the extent of arterial stiffness is associated with emphysema severity.We performed a cross-sectional study in 157 patients with COPD.We measured pulse wave velocity (a validated measure of arterial stiffness), blood pressure, smoking pack-years, glucose, cholesterol, and C-reactive protein in 157 patients with COPD. We assessed emphysema using quantitative computed tomography scanning in a subgroup of 73 patients. We found that emphysema severity was associated with arterial stiffness (r = 0.471, P < 0.001). The association was independent of smoking, age, sex, FEV(1)% predicted, highly sensitive C-reactive protein and glucose concentrations, cholesterol-high-density lipoprotein ratio, and pulse oximetry oxygen saturations.Emphysema severity is associated with arterial stiffness in patients with COPD. Similar pathophysiological processes may be involved in both lung and arterial tissue and further studies are now required to identify the mechanism underlying this newly described association.
Diagnostic test for the Prader-Willi syndrome by SNRPN expression in blood
Authors: Rachel Wevrick, Uta Francke
Journal: The Lancet (1996)

BackgroundPrader-Willi syndrome (PWS) is caused by alterations of the paternally derived chromosome 15 or by maternal uniparental disomy. The gene for the small nuclear ribonucleoprotein polypeptide N (SNRPN) is expressed only from the paternally derived chromosome 15, due to epigenetic imprinting. The SNRPN gene is not expressed in any patients with PWS regardless of the underlying cytogenetic or molecular causes.MethodsTo develop a rapid molecular diagnostic assay for PWS, we tested the expression of the SNRPN gene and a control gene in 9 patients with PWS and 40 control individuals by PCR analysis of reverse transcribed mRNA from blood leucocytes. We then tested 11 blood samples from patients with suspected PWS.FindingsSNRPN expression could readily be detected in blood leucocytes by PCR analysis in all control samples but not in samples from known PWS patients. Four suspected plus were negative for SNRPN expression were found to have chromosome 15 rearrangements, while the diagnosis of PWS was excluded in the remaining seven with normal SNRPN expression based on clinical, molecular, and cytogenetic findings.InterpretationThe SNRPN-expression test is rapid and reliable in the molecular diagnosis of Prader-Willi syndrome.
Clinical Notes on Paralysis of the Diaphragm
Authors: C. W. Suckling
Journal: BMJ (1892)

out that it supplies a valuable means of studying the manner in which conduction of impulses from the cortex through the nerve roots and plexuses to the muscles takes place; and that it is capable of still wider extension, as if, instead of pro- ducing general epilepsy, less powerful stimuli be applied to the centres for different movements, as represented in the motor cortex, it will afford a means of connecting such centres, or parts of these, with the nerve roots to which fibres proceed from these cortical motor centres.
Another patient with low back pain
Authors: B. O'Leary, G. Eminowicz, M. E. Powell, S. Pacey
Journal: BMJ (2012)

A 52 year old man was admitted to our oncology unit owing to the side effects of ongoing chemotherapy; he also gave a 10 day history of back pain. In 2008, after a bowel resection for colonic obstruction, he had been diagnosed with diffuse large B cell lymphoma. This was treated with eight cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and a complete response was achieved. He relapsed in 2010, when he presented with shortness of breath, lethargy, and weight loss. Imaging confirmed a pleural mass, lesions in the lung and liver, and lytic bone lesions. He received three cycles of RICE chemotherapy (rituximab, ifosfamide, carboplatin, and etoposide). After achieving a partial response he was treated with high dose cytarabine and etoposide chemotherapy to stabilise the disease. While he was an inpatient, with chemotherapy toxicity, he reported lower back pain and difficulty lifting his right leg, which had got worse over the past 10 days. The pain started suddenly when walking, woke him at night, and on walking radiated around to his umbilicus. On examination he was in pain—especially when he lifted the right leg—but had normal tone, power, reflexes, and sensation in both legs. A plain lumbar spine radiograph showed multiple lytic lesions, as expected. He therefore underwent magnetic resonance imaging of the whole spine (fig 1⇓). Fig 1 T2 weighted magnetic resonance imaging of lumbar spine
Another layer of ventricular heterogeneity? α1 agonists prolong repolarization in Purkinje fibers but not M-Cells
Authors: T Colatsky
Journal: Cardiovascular Research (1999)

See article by Burashnikov and Antzelevitch ([1], pages 901–908) in this issue. 

The heart is a complex organ and grows more so each day. Past research has firmly established the existence of multiple cell types that co-exist within the myocardium, each demonstrating a unique electrophysiological identity, regional localization, and coupling relationship with neighboring cells that specify the pattern of the heart beat. Within each cardiac cell type, the action potential waveform is determined by a delicate interplay among a variety of inward and outward currents flowing through distinct ion channels, pumps and transporters. The activity of each of these cellular components can in turn be modulated by drugs, hormones and neural stimulation, or modified by disease. While we are rapidly gaining an appreciation for the molecular and genetic events underlying this complexity, there remain significant gaps in our knowledge about how these events become integrated at the cell and tissue level, in health and disease.

In this issue, Alexander Burashnikov and Charles Antzelevitch add another dimension to an already complex situation by describing dramatic differences in the way ventricular cells respond to alpha-1-adrenergic receptor agonists [1]. Using strips of tissue carefully isolated from different regions of the canine myocardium, these investigators studied the effects of alpha-1-agonists on action potential duration. For the first time, they demonstrate a major pharmacologic difference between Purkinje fibers and M-cells, the two cell types that figure most prominently in discussions on the mechanism of pause-dependent proarrhythmia. Their studies show that activation of the alpha-1-receptor by either methoxamine or phenylephrine prolongs repolarization in Purkinje fibers at concentrations and cycle lengths that shorten the action potential in M-cells. This finding carries important implications for understanding how arrhythmias associated with QT interval prolongation, either congenital or induced by drugs, might occur.

Three different alpha-1-adrenergic receptors subtypes … 

* Corresponding author. Tel.: +1-609-987-1199, ext. 226; fax: +1-609-987-9393 tcolatsky{at}physiome.com