tbuckley/cabot-search huggingface dataset:
Introduction to General Toxicology
Authors: Jay M. Arena
Journal: JAMA (1976)

In this small monograph on general toxicology, with consideration for its molecular and biochemical principles, the goal is to provide briefly the three main phases of toxic action as it relates to various compounds: (1) the exposure phase, which includes factors that determine the uptake of the toxic agent from the environment, (2) the pharmacokinetic or toxokinetic phase, which includes processes such as adsorption, distribution, metabolism, and excretion factors that determine the biologic availability of the toxic substance, and (3) the pharmacodynamic or toxodynamic phase, which covers the various mechanisms involved in the induction of the toxic effect on specific organs or systems. Included in the publication are the dose-response and time-response relationships necessary for a full understanding of toxicological mechanisms, interaction among various compounds, a focus on the systemic site of action by toxic agents, which relates to the specific kind of injury produced, toxicological risks of dangerous substances
Transplacental Transmission of Malignant Melanoma
Authors: Alvan G. Foraker
Journal: JAMA (1963)

<h3>To the Editor:—</h3> In replying to a query in the Question and Answer Section ofThe Journal(<b>184</b>:324 [April 27] 1963), Dr. Joseph E. Sokal states, "One of my colleagues believes that transmission of malignant melanoma to a fetus has been reported but was unable to supply a reference." One such reference is Dargeon, H. W.; Eversole, J. W.; and Del Duca, V.: Malignant Melanoma in an Infant (<i>Cancer</i><b>3</b>:299, 1950). I performed the autopsy on this infant when I was a resident in pathology at Memorial Hospital for Cancer and Allied Disorders, New York; hence I remember the case.
Polyarteritis associated with Yersinia enterocolitica infection.
Authors: K Pile, T Kwong, J Fryer, R Laurent
Journal: Annals of the Rheumatic Diseases (1992)

A patient developed polyarteritis, predominantly affecting the muscles, 10 days after a Yersinia enterocolitica O:3 infection. Immunoperoxidase staining showed Yersinia enterocolitica O:3 antigen in the subendothelial layer of the blood vessels. This suggests that vasculitis should be considered as a rare manifestation of Yersinia enterocolitica infection.
Glucocorticoids in nano-liposomes administered intravenously and subcutaneously to adjuvant arthritis rats are superior to the free drugs in suppressing arthritis and inflammatory cytokines
Authors: Rina Ulmansky, Keren Turjeman, Moshe Baru, Galia Katzavian, Michal Harel, Alex Sigal, Yaakov Naparstek, Yechezkel Barenholz
Journal: Journal of Controlled Release (2011)
Editor of the Journal of the American Medical Association:
Authors: Albert L. Gihon
Journal: JAMA (1884)

<i>Sir</i>:—It is so very gratifying to be reproved by the venerable editor-in-chief of this journal for not having asked the prayers of the members of the Association for<i>more</i>than I did, that I am almost loath to suggest that if he will carefully read the proposed law I was so anxious to have the legislature of the State of New York given wisdom and courage (by prayer or otherwise) to enact, he will find that is " worth praying for." As many others of the members of the Association may not know the precise scope of this contemplated law I present it herewith for publication. It is indeed a surprise for me to learn that the war that such boards as those of Illinois and West Virginia "can wage against medical ignorance and incompetence will never amount to more than light skirmishing along the outposts, and is hardly worth
Hepatic Hemangioma Unexpected Bone Scan Finding
Authors: LISA Le BEL, LUCIE CARRIER, RAYMONDE CHARTRAND, DANIEL PICARD
Journal: Clinical Nuclear Medicine (1988)

A 63-year-old woman with known hepatic hemangiomas, the largest situated at the anterior surface of the left lobe, presented with bone pain. The bone scan showed an abnormal focal area of increased uptake in the left upper quadrant. Further investigations revealed that this abnormal area of uptake corresponded to the largest hepatic hemangioma. There are several plausible explanations as to why this hepatic hemangioma was visualized on the Tc-99m MDP bone scan. One explanation is that there was a significant degree of pooling of the radiopharmaceutical in this large vascular lesion. However, the intensity of uptake at 2 hours seems too important to be explained solely on the basis of pooling. Another explanation is that the hyalinized fibrous tissue stroma supporting the multiple vascular channels contained streaks of calcifications. This has been previously reported, especially as a late manifestation of large hemangiomas.
A third of surgeons in New South Wales admit to euthanasia
Authors: C. Zinn
Journal: BMJ (2001)

Euthanasia advocate Dr Philip Nitschke has called for a review of the laws on mercy killing after a study showed that more than a third of surgeons admitted hastening the deaths of terminally ill patients, mostly without explicit consent.

The anonymous poll of 683 surgeons in New South Wales, published in the Medical Journal of Australia (2001;175:511-5), found that 247 (36%) had administered high doses of painkillers with the intent of bringing death, with half of these respondents saying that there was …
Cuba: better care for stroke
Authors: Pedro O Orduñez-García, Marcos D Iraola-Ferrer, Rubén Bembibre Taboada
Journal: BMJ (2006)

EDITOR—Stroke is the third leading cause of death in Cuba. The age adjusted mortality in 2003 was 43% lower than in 1970. Rates fell moderately in 1970-9 (2.8% per year), slightly over the following two decades (0.15% per year), and more rapidly in 2000 (3.5% per year).1 This pattern shows that the impact of high rates …
Effects of arsenic on pyruvate dehydrogenase activation.
Authors: C M Schiller, B A Fowler, J S Woods
Journal: Environmental Health Perspectives (1977)

Our studies illuminate a particular site of altered pyruvate utilization by liver mitochondria isolated from arsenic-fed rats. Initially, pyruvate dehydrogenase (PDH) levels were measured before and after in vitro activation. The liver homogenates were prepared from male rats given access to deionized drinking water solutions containing 0, 20, 40, and 85 ppm arsenic as sodium arsenate (As+5) for 3 and 6 weeks. After 3 weeks, the effects of arsenic at the highest dose level were pronounced on the basal activity (before activation), with inhibition up to 48% of the control values. The total PDH (after activation) was inhibited by 14, 15, and 28% of the control values at 20, 40, and 85 ppm As+5, respectively. A similar pattern of inhibition of PDH was observed at 6 weeks, although the inhibition was lower at the highest dose. This effect is probably a reflection of mitochondrial regeneration at this time and dose. The inhibition of PDH both before and after activation suggests a direct arsenic effect on pyruvate utilization which does not involve a lipoic acid moiety. Evidence is also presented which indicates an arsenic effect on the regulating kinase and/or phosphatase. The metabolic effects of impaired mitochondrial utilization by pyruvate are also discussed.
Recommendations on Use of Prostate-Specific Antigen for Prostate Cancer Screening—Reply
Authors: Andrew M. D. Wolf, Robert J. Volk
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
Hepatitis B Virus Activates Deoxynucleotide Synthesis in Nondividing Hepatocytes by Targeting the R2 Gene
Authors: Dorit Cohen, Yaarit Adamovich, Nina Reuven, Yosef Shaul
Journal: Hepatology (2009)

Hepatitis B virus (HBV) causes liver diseases from acute hepatitis to cirrhosis and liver cancer. Currently, more than 350 million people are chronic HBV carriers, with devastating prognosis. HBV is a small enveloped noncytopathic virus, containing a circular partially double-stranded DNA genome, and exhibits strong tropism for human liver cells. Infected individuals (acute and chronic) secrete about 107 to 1011 virions per day to the bloodstream, with each infected cell releasing 50-300 viruses per day. HBV infects nondividing hepatocytes and replicates by reverse-transcribing the pregenomic RNA to DNA in the host cells. The level of deoxyribonucleotide triphosphates (dNTPs) in nondividing cells is too low to support viral replication and enable the high yield of secreted virions. Here, we report production of dNTPs by viral-dependent transcription activation of R2, the key component of ribonucleotide reductase (RNR), and show that this process is critical for the HBV life-cycle. This was found in an established HBV-positive cell line and was reproduced by HBV DNA–transduced cells, in both culture and mice. Furthermore, the viral hepatitis B X protein is essential in activating R2 expression by blocking access of Regulatory factor x1, a repressor of the R2 gene. Conclusion: Our findings demonstrate that the hepatitis B X protein is critical in infecting nonproliferating hepatocytes, which contain a low dNTP level. In addition, we provide molecular evidence for a new mechanism of HBV–host cell interaction where RNR-R2, a critical cell-cycle gene, is selectively activated in nonproliferating cells. This mechanism may set the stage for formulating a new category of anti-HBV drugs. (Hepatology 2010)
Longitudinal Assessment of Chemotherapy-Induced Structural Changes in Cerebral White Matter and Its Correlation With Impaired Cognitive Functioning
Authors: Sabine Deprez, Frederic Amant, Ann Smeets, Ronald Peeters, Alexander Leemans, Wim Van Hecke, Judith S. Verhoeven, Marie-Rose Christiaens, Joris Vandenberghe, Mathieu Vandenbulcke, Stefan Sunaert
Journal: Journal of Clinical Oncology (2011)

Purpose To uncover the neural substrate of cognitive impairment related to adjuvant chemotherapy, we studied cerebral white matter (WM) integrity before and after chemotherapy by using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. Patients and Methods Thirty-four young premenopausal women with early-stage breast cancer who were exposed to chemotherapy underwent neuropsychologic testing and DTI before the start of chemotherapy (t1) and 3 to 4 months after treatment (t2). Sixteen patients not exposed to chemotherapy and 19 age-matched healthy controls underwent the same assessment at matched intervals. In all groups, we used paired t tests to study changes in neuropsychologic test scores and whole-brain voxel-based paired t tests to study changes in WM fractional anisotropy (FA; a DTI measure that reflects WM tissue organization), with depression scores and intelligence quotient as included covariates. We correlated changes of neuropsychologic test scores with the mean change of FA for regions that survived the paired t tests in patients treated with chemotherapy. Results In contrast to controls, the chemotherapy-treated group performed significantly worse on attention tests, psychomotor speed, and memory at t2 compared with t1 (P &lt; .05). In the chemotherapy-treated group, we found significant decreases of FA in frontal, parietal, and occipital WM tracts after treatment (familywise error P &lt; .05), whereas for both control groups, FA values were the same between t1 and t2. Furthermore, performance changes in attention and verbal memory correlated with mean regional FA changes in chemotherapy-treated patients (P &lt; .05). Conclusion We report evidence of longitudinal changes in cognitive functioning and cerebral WM integrity after chemotherapy as well as an association between both.
A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liver
Authors: Barbara Akhurst, Emma J. Croager, Caroline A. Farley-Roche, Jin Kar Ong, Melissa L. Dumble, Belinda Knight, George C. Yeoh
Journal: Hepatology (2001)

Several reliable and reproducible methods are available to induce oval cells in rat liver. Effective methods often involve inhibiting proliferation in hepatocytes using an alkylating agent, then subjecting the rat to partial hepatectomy (PH). The surgery is difficult to perform reproducibly in mice. Approaches that do not include partial hepatectomy, such as administration of D-galactosamine, are ineffective in mice. We found that a choline-deficient, ethionine-supplemented (CDE) diet, which is very effective in rats, leads to high morbidity and mortality when administered to mice. This article outlines an alternative protocol by which a CDE diet can be administered to mice. This diet is shown to be highly effective for oval cell induction, without causing high mortality. It takes less time and is at least as effective as other commonly used protocols for inducing oval cells in mice. (Hepatology 2001;34:519-522.)
The dual peroxisome proliferator–activated receptor α/γ agonist tesaglitazar further improves the lipid profile in dyslipidemic subjects treated with atorvastatin
Authors: Serena Tonstad, Kjetil Retterstøl, Leiv Ose, K. Peter Öhman, Magnus B. Lindberg, Maria Svensson
Journal: Metabolism (2007)
Effect of Aldose Reductase Inhibition on Resistance to Ischemic Conduction Block in Diabetic Subjects
Authors: David E Price, Shakir M Alani, John K Wales
Journal: Diabetes Care (1991)

Objective To study the effect of aldose reductase inhibition with ponalrestat on resistance to ischemic conduction block (RICB) in diabetic subjects. Research Design And Methods Twenty-one healthy diabetic subjects without neuropathy were studied. Subjects were randomized to take either a double-blind trial of 600 mg ponalrestat or placebo once daily for 6 wk. The median nerve action potential (MNAP) and conduction velocity (NCV), before and after 20 min of forearm ischemia, were measured at the start and finish of the study. Results RICB (MNAP remaining after ischemia) decreased from 39.5 to 29.4% in the ponalrestat-treated group (P &amp;lt; 0.05) and increased from 48.1 ± 10.2 to 49.5 ± 6.5% in the placebo-treated group. MNAP and NCV were unchanged in both groups. Conclusions Aldose reductase inhibition with ponalrestat partly reverses RICB in diabetes, perhaps by improving nerve hypoxia or reducing nerve energy substrates.
Anti–TNF-α Therapy for Ankylosing Spondylitis — A Specific or Nonspecific Treatment?
Authors: Jean-Michel Dayer, Stephen M. Krane
Journal: New England Journal of Medicine (2002)

The spondyloarthropathies comprise ankylosing spondylitis, reactive arthritis, arthritis that accompanies inflammatory bowel disease, some forms of psoriatic arthritis, and undifferentiated forms of spondyloarthropathy. The report in this issue of the Journal by Gorman et al.1 focuses on ankylosing spondylitis, a seronegative spondyloarthropathy that is associated with HLA-B27 in about 90 percent of patients. HLA-B27 has a role in the binding of antigenic peptides and in their presentation to CD8+ T cells. HLA-B27–restricted cytotoxic T cells with specificity for bacteria, viral peptides, or autoantigens that cause arthritis, such as peptides derived from the HLA-B27 molecule itself, have been identified in patients . . .
True risks of paracetamol may be underestimated, say researchers
Authors: J. Wise
Journal: BMJ (2015)

A systematic review of paracetamol’s efficacy and tolerability in individual conditions is necessary because the true risks of taking the drug may have been underestimated, a UK team of researchers writes in the Annals of the Rheumatic Diseases .1

Philip Conaghan, professor at the Leeds Institute of Rheumatic and Musculoskeletal Medicine, and colleagues carried out a systematic literature review to assess the adverse event profile of paracetamol. All of the eight studies that met the inclusion criteria were cohort studies. The researchers found a dose related link between paracetamol and increasing incidence of mortality and cardiovascular, gastrointestinal, and renal adverse events, although the overall risks of these problems remained small.

Of two studies that showed mortality one found a dose response and reported an increased relative rate of …
The Structural Factor of Hypertension
Authors: Stéphane Laurent, Pierre Boutouyrie
Journal: Circulation Research (2015)

Pathophysiological studies have extensively investigated the structural factor in hypertension, including large and small artery remodeling and functional changes. Here, we review the recent literature on the alterations in small and large arteries in hypertension. We discuss the possible mechanisms underlying these abnormalities and we explain how they accompany and often precede hypertension. Finally, we propose an integrated pathophysiological approach to better understand how the cross-talk between large and small artery changes interacts in pressure wave transmission, exaggerates cardiac, brain and kidney damage, and lead to cardiovascular and renal complications. We focus on patients with essential hypertension because this is the most prevalent form of hypertension, and describe other forms of hypertension only for contrasting their characteristics with those of uncomplicated essential hypertension.
Myocardial infarction: a comparison between home and hospital care for patients.
Authors: H G Mather, D C Morgan, N G Pearson, K L Read, D B Shaw, G R Steed, M G Thorne, C J Lawrence, I S Riley
Journal: BMJ (1976)

To compare the results of home and hospital treatment in men aged under 70 years who had suffered acute myocardial infarction within 48 hours 1895 patients were considered for study in four centres in south-west England. Four-hundred-and-fifty patients were randomly allocated to receive care either at home by their family doctor or in hospital, initially in an intensive care unit. The randomised treatment groups were similar in age, history of cardiovascular disease, and incidence of hypotension when first examined. They were followed up for up to a year after onset. The mortality rate at 28 days was 12% for the random home group and 14% for the random hospital group; the corresponding figures at 330 days were 20% and 27%. On average, older patients and those without initial hypotension fared rather better under home care. The patients who underwent randomisation were similar to those whose place of care was not randomised, except that the non-randomised group contained a higher proportion of initially hypotensive patients, whose prognosis was poor wherever treated. These results confirm and extend our preliminary findings. Home care is a proper form of treatment for many patients with acute myocardial infarction, particularly those over 60 years and those with an uncomplicated attack seen by general practitioners.
A comparison of oral and inhaled steroids in patients with chronic airways obstruction: features determining response.
Authors: S M Harding, S Freedman
Journal: Thorax (1978)

Two trials comparing aerosol and oral steroid treatment were carried out in patients with chronic airways obstruction. All patients had a history of chronic productive cough and an FEV1 less than 70% predicted but did not have episodic or seasonal breathlessness with wheezing. One trial involved 18 outpatients, the other 18 inpatients. Both studies involved three consecutive treatment periods, the first with placebo aerosol, the second with active aerosol (betamethasone valerate, 800 microgram/day), and the third with oral prednisone or prednisolone (30 mg/day). Six patients showed a significant improvement in ventilatory capacity on steroids. Initial assessment included a comprehensive history using a questionnaire, skin tests, blood and sputum eosinophil counts, and chest radiography. In addition, for the inpatients, response to isoprenaline, daily sputum volume, and PaCO2 were measured. Only blood eosinophilia and variability in ventilatory capacity during the placebo period seemed indicative of a likely response to steroids. However, there was a large overlap between various features on assessment in the responders and non-responders, and the management of every patient with chronic airways obstruction should include a controlled trial of steroids. The steroid aerosol produced a good improvement in ventilatory capacity in the responsive patients who were hospitalised and this was thought to be helped by supervision of aerosol technique. Such an aerosol could therefore be used for a steroid trial although oral steroids were found to give a more definitive response.
Role of renal nerves, angiotensin II, and prostaglandins in the antinatriuretic response to acute hypercapnic acidosis in the dog.
Authors: R J Anderson, W L Henrich, P A Gross, M A Dillingham
Journal: Circulation Research (1982)

Although clinical studies suggest that chronic hypercapnic acidosis may be associated with renal sodium retention, little information is available on the effect of acute hypercapnic acidosis on renal sodium excretion. We, therefore, increased PCO2 from 23 to 74 mm Hg in anesthetized dogs and observed a marked antinatriuresis as absolute sodium excretion (235 to 60 muEq/min, P less than 0.001) and fractional excretion of sodium (4.0 to 1.2 %, P less than 0.02) decreased significantly. This decrease in sodium excretion occurred independent of consistent changes in renal perfusion pressure, PO2, glomerular filtration rate, renal blood flow, extraction of P-aminohippuric acid, and filtration fraction. The antinatriuretic response to acute hypercapnic acidosis could be attenuated significantly by surgical renal denervation, intrarenal phenoxybenzamine, and by intrarenal infusion of 1-sarcosine,8-glycine angiotensin II. Administration of 10 mg/kg indomethacin enhanced the antinatriuretic response to hypercapnic acidosis in denervated kidneys. These results suggest that renal alpha-adrenergic nerves and the renal angiotensin system result in an antinatriuretic effect during acute hypercapnic acidosis. Renal prostaglandins or related substances may serve to attenuate this antinatriuretic response.