tbuckley/cabot-search huggingface dataset:
Secretory Otitis Media: The Cantekin Affair-Reply
Authors: Drummond Rennie
Journal: JAMA (1992)

<h3>In Reply.</h3> —Drs Gates and Klein accuse me of "emphasizing the sensational and personal aspects rather than the science of the dispute." They ignore the obvious fact that our readers require explanation as to why we are taking the exceptional step of publishing a reanalysis of the trial data and the extraordinary one of doing so 6 years later. It should be clear that the reasons were not merely scientific, and I could not have properly focused on the "problems related to peer review and publication" without recording the nature of those problems. The other achievements of the Pittsburgh group, which<i>JAMA</i>has recognized by publishing their recent work,<sup>1,2</sup>are not at issue. Readers of Mandel et al<sup>3</sup>will look in vain for any acknowledgment concerning Bluestone's "honoraria and grant support from pharmaceutical companies" so the statement by Gates and Klein that these were "identified" is astonishing. The
Inquiry into adverse events in trial blames drug, not study design
Authors: Susan Mayor
Journal: BMJ (2006)

A preliminary investigation of a UK trial in which six healthy volunteers became critically ill said this was probably due to effects of the drug in humans not predicted by animal studies. But the report stopped short of questioning how the study was carried out.

The investigation into the phase I trial of the monoclonal antibody TGN1412, carried out by the Medicines and Healthcare Products Regulatory Agency (MHRA), the body that approves clinical trials in England, said the trial was run according to the agreed protocol, using the correct dose. It also found no evidence of a manufacturing problem or contamination of the product given to the trial volunteers.

The MHRA's report did not comment on suggestions that it might have been more prudent to have tested the drug in one volunteer at a time, leaving enough time to observe any adverse effects before giving it to another person, rather than giving it to the whole group at once ( BMJ 2006;332: 683, 25 Mar).

The protocol for the trial …
Hormone Replacement Therapy and Sleep-disordered Breathing
Authors: Eyal Shahar, Susan Redline, Terry Young, Lori L. Boland, Carol M. Baldwin, F. Javier Nieto, George T. O'Connor, David M. Rapoport, John A. Robbins
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Disordered breathing during sleep is more common among postmenopausal women than among their premenopausal counterparts, possibly because of declining levels of estrogen and progesterone. We examined the relationship between the use of replacement hormones and sleep-disordered breathing in a sample of 2,852 noninstitutionalized women, 50 years of age or older, who participated in the Sleep Heart Health Study. The frequency of apneas and hypopneas per hour of sleep (apnea–hypopnea index) was determined by unattended, single-night polysomnography at the participant's home. The prevalence of sleep-disordered breathing (apnea–hypopnea index of 15 or more) among hormone users (61 of 907) was approximately half the prevalence among nonusers (286 of 1,945). Multivariable adjustment for known determinants of the disorder, including age, body mass index, and neck circumference, has attenuated the association, but only moderately (adjusted odds ratio, 0.55; 95% confidence interval, 0.41 to 0.75). The inverse association between hormone use and sleep-disordered breathing was evident in various subgroups and was particularly strong among women 50 to 59 years old (adjusted odds ratio, 0.36; 95% confidence interval, 0.21 to 0.60). If the observed associations are causal, hormone replacement therapy could have a role in preventing or alleviating sleep-disordered breathing.
Trial protocols: time for more than tinkering
Authors: James Penston
Journal: BMJ (2005)

EDITOR—The BMJ 's recent requirement that authors include a trial protocol when submitting research papers for publication seems reasonable to expose deviations from the original protocol.1 However, Abbasi and Jones's comment that “identifying deviation from the protocol is another important step in ensuring that the findings of a study are reported with honesty and transparency” rings hollow.

What are …
Initial Evaluation of Rectal Bleeding in Young Persons: A Cost-Effectiveness Analysis
Authors: James D. Lewis, Alphonso Brown, A. Russell Localio, J. Sanford Schwartz
Journal: Annals of Internal Medicine (2002)

Background: Evaluation of rectal bleeding in young patients is a frequent diagnostic challenge. Objective: To determine the relative cost-effectiveness of alternative diagnostic strategies for young patients with rectal bleeding. Design: Cost-effectiveness analysis using a Markov model. Data Sources: Probability estimates were based on published medical literature. Cost estimates were based on Medicare reimbursement rates and published medical literature. Target Population: Persons 25 to 45 years of age with otherwise asymptomatic rectal bleeding. Time Horizon: The patient's lifetime. Perspective: Modified societal perspective. Interventions: Diagnostic strategies included no evaluation, colonoscopy, flexible sigmoidoscopy, barium enema, anoscopy, or any feasible combination of these procedures. Outcome Measures: Life expectancy and costs. Results of Base-Case Analysis: For 35-year-old patients, the no-evaluation strategy yielded the least life expectancy. The incremental cost-effectiveness of flexible sigmoidoscopy compared with no evaluation or with any strategy incorporating anoscopy (followed by further evaluation if no anal disease was found on anoscopy) was less than $5300 per year of life gained. A strategy of flexible sigmoidoscopy plus barium enema yielded the greatest life expectancy, with an incremental cost of $23 918 per additional life-year gained compared with flexible sigmoidoscopy alone. Results of Sensitivity Analysis: As patient age at presentation of rectal bleeding increased, evaluation of the entire colon became more cost-effective. The incremental cost-effectiveness of flexible sigmoidoscopy plus barium enema compared with colonoscopy was sensitive to estimates of the sensitivity of the tests. In a probabilistic sensitivity analysis comparing flexible sigmoidoscopy with anoscopy followed by flexible sigmoidoscopy if needed, the middle 95th percentile of the distribution of the incremental cost-effectiveness ratios ranged from flexible sigmoidoscopy yielding an increased life expectancy at reduced cost to $52 158 per year of life gained (mean, $11 461 per year of life saved). Conclusions: Evaluation of the colon of persons 25 to 45 years of age with otherwise asymptomatic rectal bleeding increases the life expectancy at a cost comparable to that of colon cancer screening.
Nuclear Changes in Squamous Cells from Buccal Mucosa in Pernicious Anaemia
Authors: P. C. Farrant
Journal: BMJ (1960)

VACCINATION AGAINST POLIOMYELITISA good response to a fourth dose of the inactivated vaccine was found in most of the children.No poliovirus inhibitors could be f9und in the faeces of these children either before or after the fourth dose.A comparison was made of two different methods of titrating poliomyelitis antibodies.Our thanks are due to the children who participated in this investigation and to their parents for permission to take serum samples.
Ultrasonic Catheters Give Cardiologists Boost in Observing Internal Blood Vessels
Authors: Marsha F. Goldsmith
Journal: JAMA (1990)

MINIATURE ultrasonic probes are showing cardiologists more about coronary and peripheral vasculature than ever before. The new devices, developed separately during the last several years by four northern California-based companies, combine a catheter with an ultrasound transducer that is based on a wafer-thin chip to produce ultrasharp cross-sectional images. The resulting views of arterial narrowing delineate fibrous plaque as well as soft fatty plaque much better than such earlier techniques as contrast angiography or computed resonance imaging, say investigators. The new technique also provides an image of the arterial wall and enables measurement of the mass of the atheroma—both beyond the capability of angiography, they point out. The companies at work on this new device are Diasonics, which is located in Milpitas, working in conjunction with Boston Scientific; Endosonics, in Pleasanton; Cardiovascular Imaging Systems, in Sunnyvale; and InterTherapy, in Costa Mesa. The electronic innovation necessary to create these new devices
L-Asparaginase: Clinical, Biochemical, Pharmacological, and Immunological Studies
Authors: ROBERT L. CAPIZZI
Journal: Annals of Internal Medicine (1971)

Forty patients with acute leukemia were treated with Intravenous L-asparaginase in doses ranging from 10 to 1,000 international units/kg body weight per day for 2 to 20 days. Most had long-standing disease and had exhausted conventional therapy. The remission rate appeared to be unaffected by dose, schedule, or previous chemotherapy. There was a 66% response rate for acute lymphoblastic leukemia and an approximately 12% response rate for nonlymphocytic leukemia. Second and third remissions were obtained. Toxicity was not strictly dose related and consisted of fever, anorexia, nausea, vomiting, decreased protein synthesis, biochemical hepatic dysfunction, elevated blood ammonia, nonketotic hyperglycemia, and anaphylaxis. Although there were two deaths directly attributed to L-asparaginase, most patients tolerated the enzyme well with very little impairment of performance status. The rapid clearance of plasma enzyme and the development of passive hemagglutinating and reagin types of antibodies are correlated with the development of anaphylaxis. The relationship of plasma L-asparagine to disease status is discussed.
Regulation of Shear Stress in the Canine Coronary Microcirculation
Authors: David W. Stepp, Yasuhiro Nishikawa, William M. Chilian
Journal: Circulation (1999)

Background —Physical forces, such as pressure and flow, are well known to affect vascular function in the coronary circulation. Increases in shear stress produce vasodilation in coronary arterioles in vitro, and constant-flow preparations suggest a role for shear stress–induced vasodilation during adjustments to metabolic demand in vivo. Hypothetically, the regulation of shear stress can be viewed as a negative feedback control scheme (increased velocity → increased shear → vasodilation → decreased velocity → shear normalized). Therefore, we hypothesized that shear stress would be at least partially regulated during conditions of elevated flow. Methods and Results —We used fluorescence microangiography to measure microvascular diameters and velocities in the coronary circulation in vivo and used these variables to calculate shear stress. Measurements were obtained under basal conditions, during maximal coronary blood flow, and after inhibition of NO synthase. Basal shear stress in the coronary circulation averaged 10 dyn/cm 2 in small arteries and 19 dyn/cm 2 in arterioles. Regulation of shear stress was observed in small arteries during adenosine-induced increases in coronary blood flow, but arterioles showed minimal regulation. NO synthase blockade had no effect on basal shear stress but completely abolished its regulation in small arteries during vasodilation. Conclusions —Our data provide the first quantitative estimates of microvascular shear stress in the coronary circulation. Moreover, our results suggest that shear stress in small coronary arteries is regulated by NO release from the endothelium.
Adding HPV testing to cytology screening reduced ≥ grade 3 cervical intraepithelial neoplasia at 5 years
Authors: Brian Budenholzer
Journal: Annals of Internal Medicine (2012)

Source Citation Rijkaart DC, Berkhof J, Rozendaal L, et al. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol. 2012;13:78-88. 22177579
Can Imaging Help Revive the Autopsy?
Authors: M. J. Friedrich
Journal: JAMA (2012)

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
Abstract 4189: The Amount of Myocardial Fibrosis by Contrast-Enhanced Magnetic Resonance Imaging Predicts Mortality Late after Aortic Valve Replacement in Patients with Severe Aortic Valve Disease: Validation against Quantitative Histopathology
Authors: Clerio F Azevedo, Marcelo Nigri, Flávio Tarasoutchi, Pablo M Pommerantzeff, Roney O Sampaio, José R Parga, Luiz F Ávila, Guilherme S Spina, Max Grinberg, Maria L Higuchi, Carlos E Rochitte
Journal: Circulation (2008)

INTRODUCTION: Severe aortic valve disease (AVD) is characterized by progressive accumulation of interstitial myocardial fibrosis (MF). The relationship between the amount of MF and mortality after aortic valve replacement (AVR) surgery in largely unknown. OBJECTIVES: Determine whether the quantitative assessment of MF by delayed-enhanced magnetic resonance imaging (deMRI) can predict mortality late after AVR in patients with severe AVD. METHODS: Fifty-four patients scheduled to undergo AVR surgery were examined by cine and deMRI. From the deMRI dataset, the amount of MF was automatically determined as the sum of pixels with signal intensity (SI) above a threshold value calculated as: mean SI of total myocardium + 2SD of a remote area SI + 2SD of air SI. The remote area was manually delineated in a myocardial region free of hyper-enhancement. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during AVR surgery and stained with picrosirius red. Patients were classified in 3 groups according to the degree of MF accumulation. A second deMRI study was performed 27 ± 22 months after surgery to assess LV functional recovery and all patients were followed for 43 ± 23 months to evaluate survival after AVR. RESULTS: There was a good correlation between the values of MF measured by MRI and those obtained by histopathology (r = 0.69; y = −3.10x + 13.0; p &lt; 0.0001). The amount of MF, either by MRI or by histopathology, exhibited a significant inverse correlation with LV ejection fraction before surgery (r = −0.63 e −0.67 respectively; p&lt;0.0001). Additionally, the amount of MF displayed a significant inverse correlation with the degree of LV functional recovery after AVR (r = −0.42, p = 0.04 for histopathology; r = −0.47, p = 0.02 for deMRI). Most importantly, Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse survival after AVR surgery (log-rank test: χ2=6.32; p=0.01 for histopathology; χ2=5.85; p=0.02 for deMRI). CONCLUSIONS: DeMRI allows for the non-invasive quantification of MF with good accuracy when compared with histopathology in patients with severe AVD. Most importantly, quantification of MF can predict LV functional recovery and all-cause mortality late after AVR surgery.
Editor's Note: Sulforaphane Enhances the Therapeutic Potential of TRAIL in Prostate Cancer Orthotopic Model through Regulation of Apoptosis, Metastasis, and Angiogenesis
Authors: Sharmila Shankar, Suthakar Ganapathy, Rakesh K. Srivastava
Journal: Clinical Cancer Research (2020)

Purpose:  The purpose of this study was to examine the molecular mechanisms by which sulforaphane enhances the therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in prostate cancer.   Experimental Design:  Cell viability and apoptosis assays were done by XTT and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Tumor-bearing mice were treated with vehicle, sulforaphane, TRAIL, and sulforaphane plus TRAIL. Markers of apoptosis, angiogenesis, and metastasis were measured by immunohistochemistry.   Results:  Sulforaphane enhanced the therapeutic potential of TRAIL in PC-3 cells and sensitized TRAIL-resistant LNCaP cells. Sulforaphane-induced apoptosis in PC-3 cells correlated with the generation of intracellular reactive oxygen species (ROS), collapse of mitochondrial membrane potential, activation of caspase-3 and caspase-9, and up-regulation of DR4 and DR5. Sulforaphane induced the expression of Bax, Bak, Bim, and Noxa and inhibited the expression of Bcl-2, Bcl-X L , and Mcl-1. The quenching of ROS generation with antioxidant  N -acetyl-l-cysteine conferred significant protection against sulforaphane-induced ROS generation, mitochondrial membrane potential disruption, caspase-3 activation, and apoptosis. Sulforaphane inhibited growth of orthotopically implanted PC-3 tumors by inducing apoptosis and inhibiting proliferation and also enhanced the antitumor activity of TRAIL. Sulforaphane up-regulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and Bak and inhibited the activation of nuclear factor-κB P13K/AKT and MEK/ERK pathways in tumor tissues. The combination of sulforaphane and TRAIL was more effective in inhibiting markers of angiogenesis and metastasis and activating FOXO3a transcription factor than single agent alone.   Conclusions:  The ability of sulforaphane to inhibit tumor growth, metastasis, and angiogenesis and to enhance the therapeutic potential of TRAIL suggests that sulforaphane alone or in combination with TRAIL can be used for the management of prostate cancer.
Absence of morphologic correlation between chemical toxicity and chemical carcinogenesis.
Authors: J Huff
Journal: Environmental Health Perspectives (1993)

The experimental data set used to evaluate site-specific histopathologic correspondence between the morphologic end points of toxicity and carcinogenicity comprises 130 chemical carcinogenesis studies. Nearly 1500 sex-species-exposure-group experiments were evaluated for a) evidence of toxicity or/and carcinogenicity, b) dose-response relationships, c) site-specific correlations of toxicity and carcinogenicity, and d) correspondence with Salmonella mutagenicity. The major conclusions are that chemicals evaluated for long-term toxicity and carcinogenicity in experimental animals divide typically and consistently into three categories: a) chemicals causing organ toxicity without cancer, b) chemicals causing site-specific cancer with no associated toxicity, and c) chemicals causing both toxicity and cancer in the same organ. Few chemicals overall (and none in this data set) fit the remaining group that cause neither toxicity nor carcinogenicity under these protocol conditions. Mutagenicity exhibited no consistent pattern with any of these groupings. Only 7 of 53 "positive" chemicals had target organ toxicity at all sites of carcinogenicity. Just three chemicals showed carcinogenic effects at the highest exposure concentrations without supporting evidence of tumors at the lower levels. From these comparative morphological analyses, and for almost all cases, available data do not support a correlation between chemically induced toxicity or regenerative phenomena and carcinogenicity. Consequently, until scientific knowledge about molecular mechanisms of chemical carcinogenesis becomes better understood and generally accepted, attempts to use toxicity findings to modify risk assessment processes will be fraught with uncertainty and thus could have a negative impact on public health.
Diabetic ketoacidosis does not precipitate haemolysis in patients with the Mediterranean variant of glucose-6-phosphate dehydrogenase deficiency.
Authors: O Shalev, A Wollner, J Menczel
Journal: BMJ (1984)

Diabetic ketoacidosis is traditionally stated as being capable of precipitating haemolysis in patients deficient in glucose-6-phosphate dehydrogenase (G6PD). This, however, is based on only a few case reports with inadequate documentation. A study was therefore conducted to review the subject in people with the Mediterranean variant of G6PD deficiency. Perusal of the medical records for the years 1970-82 yielded 15 patients with G6PD deficiency who had been admitted to hospital for a total of 36 episodes of diabetic ketoacidosis. Ten of these episodes had been complicated by haemolytic anaemia, but in every one there was unequivocal evidence of either concurrent bacterial infection or inadvertent ingestion of drugs, either of which might induce haemolysis in G6PD deficient patients. In the remaining 26 episodes there was no evidence of developing or established haemolytic anaemia. From these findings diabetic ketoacidosis should not be regarded as a risk factor for haemolysis in the Mediterranean variant of G6PD deficiency.
Bone-Marrow Failure Due to Relative Nutritional Deficiency in Cooley's Hemolytic Anemia
Authors: James H. Jandl, Mortimer S. Greenberg
Journal: New England Journal of Medicine (1959)

SINCE the observations of Lyngar1 and Owren2 on the mechanism of intercurrent anemic crises in hereditary spherocytosis, it has been widely recognized that bone-marrow failure often underlies such crises and may complicate the course of various other chronic hemolytic disorders.3 4 5 6 7 Such "aplastic crises" are usually self-limited, frequently lasting ten to fourteen days, and are accompanied by an apparent arrest of early erythroid precursors (stem cells), resulting in erythroid marrow hypoplasia and reticulocytopenia. This acute inhibition of stem-cell proliferation is usually caused by infection, thus accounting for the familial nature of anemic crises in some patients afflicted with hereditary hemolytic disorders. . . .