tbuckley/cabot-search huggingface dataset:
Molecular Diagnosis of Thiopurine S-Methyltransferase Deficiency
Authors: Robert D. Blank
Journal: Annals of Internal Medicine (1997)

Letters1 December 1997Molecular Diagnosis of Thiopurine S-Methyltransferase DeficiencyRobert D. Blank, MD, PhDRobert D. Blank, MD, PhDThe Hospital for Special Surgery; New York, NY 10021Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-11-199712010-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Yates and colleagues' recent paper [1] on polymerase chain reaction (PCR)-based diagnosis of thiopurine S-methyltransferase (TPM) deficiency and the accompanying editorial [2] with great interest. The authors have shown that the presence of any of three missense mutations can be detected with a PCR-based assay. They have further demonstrated that genotype is highly correlated with measured enzyme activity. However, Yates and colleagues did not address several points worthy of comment. They did not explicitly cite studies showing that the sequence variants studied segregate with diminished enzyme activity. Such linkage studies would be particularly interesting in ...References1. Yates CR, Krynetski EY, Loennechen T, Fessing MY, Tai HL, Pui CH, et al. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Ann Intern Med. 1997; 126:608-14. Google Scholar2. Vesell ES. Therapeutic lessons from pharmacogenetics [Editorial]. Ann Intern Med. 1997; 126:653-4. Google Scholar Author, Article, and Disclosure InformationAuthors: Robert D. Blank, MD, PhDAffiliations: The Hospital for Special Surgery; New York, NY 10021 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDevelopment of duplex-crossed allele-specific PCR targeting of TPMT*3B and *3C using crossed allele-specific blockers to eliminate non-specific amplification 1 December 1997Volume 127, Issue 11Page: 1041KeywordsClinical laboratoriesDrugsEnzymesMutationPhenotypesPolymerase chain reaction ePublished: 15 August 2000 Issue Published: 1 December 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
1121-54 Implications of the “watermelon seeding” phenomenon during coronary interventions for in-stent restenosis insights from the restenosis intrastent balloon angioplasty versus elective stenting (RIBS) randomized trial
Authors: Manuel Gomez-Recio, Cesar Moris, Luis Insa, Isabel Calvo, Jose M Hernández, Jose A Bullones, Vasco Gama-Ribeiro, A Leitao-Marques, Armando Bethencourt, Roman Lezaun, Juan Angel, Jose R Lopez-Minguez, Maria J Pérez-Vizcayno, Fernando Alfonso
Journal: Journal of the American College of Cardiology (2004)
Ambulatory Monitoring of Congestive Heart Failure by Multiple Bioelectric Impedance Vectors
Authors: Dirar S. Khoury, Mihir Naware, Jeff Siou, Andreas Blomqvist, Nilesh S. Mathuria, Jianwen Wang, Hue-Teh Shih, Sherif F. Nagueh, Dorin Panescu
Journal: Journal of the American College of Cardiology (2009)
Time to erase the line?
Authors: Niall L Cox
Journal: BMJ (2007)

As a longstanding anti-choicer, I commend Gornall on a balanced and informative article on abortion.1 It got me wondering if the abortion debate isn't all a bit pointless. Pro-choicers and pro-lifers disagree profoundly on whether children can be treated differently depending on whether it's before or after they're born. The “right” answer to this seems to depend on what part of …
CARBON MONOXID ASPHYXIATION FROM MOTOR EXHAUST
Authors: Paul W. Emerson
Journal: JAMA (1924)

<h3>To the Editor:</h3> —I wish to report three cases of poisoning by motor gas because, while the newspapers are reporting deaths from this cause all the time, few people realize how insidious this poison is or that children may succumb in a few minutes to an amount that may be unnoticed by adults. Dr. H., preparatory to setting out for his office on the morning of Nov. 13, 1923, opened the door of his garage, which is in the basement of his residence, and started the engine, when a neighbor came into the yard. The doctor left his engine running idle and went out. While he was talking, his two children and a neighbor's child were playing about. Their ages varied from 4 to 5½ years. In certainly less than ten minutes he returned to the garage, the doors of which were now closed, and on looking through the door
Significant increase in trisomy 21 in Berlin nine months after the Chernobyl reactor accident: temporal correlation or causal relation?
Authors: K Sperling, J Pelz, R-D Wegner, A Dorries, A Gruters, M Mikkelsen
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b>: To assess whether the increased prevalence of trisomy 21 in West Berlin in January 1987 might have been causally related to exposure to ionising radiation as a result of the Chernobyl reactor accident or was merely a chance event. <b>Design</b> : Analysis of monthly prevalence of trisomy 21 in West Berlin from January 1980 to20December 1989. <b>Setting</b> : Confines of West Berlin. <b>Results</b> : Owing to the former "island" situation of West Berlin and its well organised health services, ascertainment of trisomy 21 was thought to be almost complete. A cluster of 12 cases occurred in January 1987 as compared with two or three expected. After exclusion of factors that might have explained the increase, including maternal age distribution, only exposure to radiation as a result of the Chernobyl reactor accident remained. In six of seven cases that could be studied cytogenetically the extra chromosome was of maternal origin, confirming that nondisjunction had occurred at about the time of conception. <b>Conclusion</b> : On the basis of two assumptions - (a) that maternal meiosis is an error prone process susceptible to exogenous factors at the time of conception; (b) that owing to the high prevalence of iodine deficiency in Berlin a large amount of iodine-131 would have been accumulated over a short period - it is concluded that the increased prevalence of trisomy 21 in West Berlin in January 1987 was causally related to a short period of exposure to ionising radiation as a result of the Chernobyl reactor accident. A global risk study on the health implications of the Chernobyl reactor accident in 1986 concluded that "probably no adverse health effect will be manifest by epidemiological analysis."*RF 1*
The Hillsborough tragedy.
Authors: A. Page
Journal: BMJ (1992)

ground.2Damage to the mitral valve may occur when the heart is violently compressed at the end ofdiastole, when the left ventricle is full.'This may cause rupture of the chordae tendineae or papillary muscles or damage to the valve leaflets themselves.4In severe cases symptoms may occur directly after the injury, but in some cases they may be delayed for several years.'Our patient's posterior mitral valve prolapse was probably due to damage to the chordae tendineae sustained during the crush at the football ground.Such cases have medicolegal implications as mitral valve surgery may become necessary.
Histological Assessment of 526 Symptomatic Carotid Plaques in Relation to the Nature and Timing of Ischemic Symptoms
Authors: J.N.E. Redgrave, J.K. Lovett, P.J. Gallagher, P.M. Rothwell
Journal: Circulation (2006)

Atherosclerotic plaque at the carotid bifurcation is often associated with transient ischemic attack (TIA) and ischemic stroke, but the mechanisms are not completely understood. Previous histological studies have been too small or insufficiently detailed to reliably determine the temporal course of features of plaque instability or to stratify analyses by the nature of presenting symptoms.We performed the largest-ever histological study of symptomatic carotid plaques from consecutive patients (n=526) undergoing endarterectomy and related detailed reproducible histological assessments to the nature and timing of presenting symptoms. There was a high prevalence of many features of coronary-type plaque instability. Dense plaque inflammation (especially infiltration with macrophages) was the feature most strongly associated with both cap rupture (odds ratio 3.39, 95% confidence interval 2.31 to 4.98, P<0.001) and time since stroke (P=0.001). Strong negative associations with time since stroke were also seen for cap rupture (P=0.02), overall plaque inflammation (P=0.003), and "unstable plaque" (P=0.001). Although plaques removed < or =60 days after the most recent event were more unstable after a stroke than after a TIA, the instability persisted after a TIA, and plaques removed >180 days after most recent event were less unstable after a stroke than after a TIA (plaque inflammation: < or =60 days, odds ratio 2.33 [95% confidence interval 0.76 to 7.19]; >180 days, 0.36 [0.16 to 0.84]; P=0.008; unstable plaque: odds ratio 3.27 [95% confidence interval 0.93 to 11.50] versus 0.74 [0.33 to 1.69], P=0.05).Pathology of recently symptomatic carotid plaques is similar to that of culprit coronary plaques, with strong correlations between macrophage infiltration and plaque instability. The tendency for plaque inflammation and overall instability to persist with time after a TIA but to decrease with time after a stroke suggests that the nature of the underlying pathology may differ.
Hyperdynamic Myocardial Response to Beta-Adrenergic Stimulation in Patients With Chest Pain and Normal Coronary Arteries
Authors: Juraj Madaric, Jozef Bartunek, Katia Verhamme, Martin Penicka, Eddy Van Schuerbeeck, Paul Nellens, Guy R. Heyndrickx, William Wijns, Marc Vanderheyden, Bernard De Bruyne
Journal: Journal of the American College of Cardiology (2005)
Management of Stable Angina
Authors: Wilbert S. Aronow
Journal: New England Journal of Medicine (1973)

THE mechanism of the production of angina pectoris remains unclear.1 However, angina pectoris due to coronary-artery disease is generally considered to be chest pain due to myocardial ischemia that occurs because the myocardial oxygen demand exceeds the myocardial oxygen supply.The most sensible approach to the problem of coronary heart disease is the reduction, when possible, of the many risk factors that predispose to the development of the disease. However, once angina pectoris develops, the physician is faced with the problem of providing pain relief to the patient. In addition to relief of pain, an ideal antianginal drug would also . . .
The hepatocellular uptake and biliary excretion of endotoxin in the rat
Authors: Shyamal K. Maitra, Daniel Rachmilewitz, David Eberle, Neil Kaplowitz
Journal: Hepatology (1981)

Endotoxin is known to cause a dose-dependent impairment of hepatic bile secretion, organic anion excretion, and activity of Na + , K + -activated ATPase. Since it is possible that this impaired excretory function is a result of direct interaction of endotoxin with hepatocytes, we examined: (a) the excretion of endotoxin into bile, and (b) its association with an hepatocyte-enriched, Kupffer cell-depleted population of liver cells. Escherichia coli 0127:B8 endotoxin (17 to 54 μg per 100 gm body weight) was given i.v. to male Sprague Dawley rats and bile collected up to 48 hr. The expected significant decrease in bile secretion was seen, confirming the biological effectiveness of the endotoxin. Endotoxin was quantitated by a gas chromatography/mass spectroscopy method which detects the β-hydroxymyristic acid in the lipid A moiety of endotoxin. Approximately 7% of the administered dose of endotoxin was recovered as β-hydroxymyristic acid in bile in the 48 hr following injection. Approximately two thirds of the administered dose of endotoxin was recovered as β-hydroxymyristic acid in the whole liver. Further analysis of the β-hydroxymyristic acid in bile and liver by Folch extraction and thin-layer chromatography was performed. The β-hydroxymyristic acid in bile was associated with polar and nonpolar metabolites of endotoxin. The β-hydroxymyristic acid recovered in the liver distributed similarly in Folch extraction to intact endotoxin added in vitro. Endotoxin quantitated as β-hydroxymyristic acid was measured in whole liver homogenate and hepatocyte-enriched preparations 3 hr following i.v. administration. The mass abundance by gas chromatography/mass spectrometry of β-hydroxymyristic acid per 10 6 hepatocytes was similar in crude liver homogenate and the hepatocyte-enriched fractions indicating the presence of substantial amounts of β-hydroxymyristic acid in association with parenchymal liver cells. Thus, our studies indicate that the bulk of the β-hydroxymyristic acid of endotoxin given i.v. to rats is found in hepatocytes in a form suggesting minimal degradation of the endotoxin. A small proportion of the β-hydroxymyristic acid associated with the endotoxin in the liver is then released slowly into bile as a complex mixture of polar and nonpolar metabolites of endotoxin.
Doctors' revalidation bags
Authors: M. Lakhani
Journal: BMJ (2011)

GP appraiser Mayur Lakhani finds doctors’ revalidation folders strangely evocative



Duncan Smith

I have been a GP appraiser for more than 10 years now. Appraisees have to deliver their folders to the appraiser’s surgery. During this time, the packaging that these folders arrive in has fascinated me. Many folders arrive in shopping bags, which range from high street fashion brands …
Efficacy and Cost Effectiveness of Adjuvant Chemotherapy in Women with Node-Negative Breast Cancer
Authors: Bruce E. Hillner, Thomas J. Smith
Journal: New England Journal of Medicine (1991)

In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated.Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment.For the 45-year-old woman, the base-line analysis found an average lifetime benefit from chemotherapy of 5.1 quality-months at a cost of $15,400 per quality-year. The 60-year-old women gained 4.0 quality-months at a cost of $18,800 per quality-year. Under the more and less optimistic scenarios, the benefit of chemotherapy varied from 1.4 to 14.0 quality-months for both groups.Chemotherapy substantially increases the quality-adjusted life expectancy of an average woman at a cost comparable to that of other widely accepted therapies. This benefit decreases markedly if the changes in long-term survival are less than in disease-free survival. Given its uncertain duration, the benefit may be too small for many women to choose chemotherapy. Selective use of chemotherapy to maximize the benefit to individual patients may be possible with refinements in risk stratification and explicit assessment of the patients' risk preferences.
Unilateral Gallium-67 Uptake in Primary Tuberculosis of the Major Salivary Glands
Authors: HEINER BIHL, HEINZ MAIER
Journal: Clinical Nuclear Medicine (1987)

Unilateral radionuclide accumulation in salivary glands is an uncommon finding on gallium scintigraphy. The differential diagnosis includes malignant tumors and inflammatory processes of these organs. Two cases of unilateral gallium uptake of the parotid and submandibular gland respectively, verified as solitary tuberculosis, are presented, together with the correlative findings of Tc-99m pertechnetate scintigraphy, sialography, and sonography. None of these imaging modalities is specific enough to provide pathognomonic signs for tuberculosis. When assessing unilateral gallium uptake of the salivary glands, one should be aware of the possibility of tuberculosis.
Value of Screening for Markers of Hepatitis in Dialysis Units
Authors: Athol J. Ware, Nancy L. Gorder, Lawrence E. Gurian, Clark Douglas, James W. Shorey, Thomas Parker
Journal: Hepatology (1983)

The value of monitoring the serum activity of SGOT, as well as markers of hepatitis B virus and hepatitis A virus infections, in the patients and staff of two dialysis units has been assessed retrospectively. Sera were checked each month for SGOT and HBsAg on 406 patients and 170 staff members over a 4-year period. Anti-HBc, anti-HBs, and anti-hepatitis A antibodies were assayed on the stored sera. Only 30% of the patients had normal SGOT values (&lt;65 units per ml) on all occasions. Most of the abnormal values were &lt;100 units per ml and could not be explained. Viral hepatitis was a reasonable explanation for only half of those instances where the SGOT value was greater than 100 units per ml. Hepatitis A virus contributed nothing to the problem of dialysis-associated liver disease. Testing for HBsAg alone missed approximately 40% of the hepatitis B events acquired in the unit. Only two of these episodes were of epidemiologic importance, however, because the rest were recognized only after there was serologic resolution of the infection. There was a high frequency of potentially “false positive” reactions with all the antibodies tested. It is not cost-effective to monitor dialysis patients and staff regularly with anti-HBc, anti-HBs, or antibodies against hepatitis A. Initial screening with anti-HBc and anti-HBs on entry to the unit is of value but weak positive results must be interpreted with caution since approximately half of such results will prove to be nonspecific.
Role of the Renin-Angiotensin System on the Parathyroid Hormone–Related Protein Overexpression Induced by Nephrotoxic Acute Renal Failure in the Rat
Authors: Arantxa Ortega, David Rámila, Adriana Izquierdo, Laura González, Antonio Barat, Rosa Gazapo, Ricardo J. Bosch, Pedro Esbrit
Journal: Journal of the American Society of Nephrology (2005)

Parathyroid hormone-related protein (PTHrP), a mitogenic factor for renal cells, is overexpressed in acute renal failure (ARF). Recent data support an association between PTHrP and the renin-angiotensin system in the damaged kidney. The effects of angiotensin II (Ang II) inhibitors (quinapril, enalapril, and/or losartan) on PTHrP and the PTH1 receptor (PTH1R) expression in rats with either folic acid (FA)- or gentamicin-induced ARF were analyzed. The decreased renal function and the PTHrP upregulation and PTH1R downregulation induced by the nephrotoxins were inhibited by the Ang II blockers. In tubuloepithelial cells NRK-52E, the rapid (10 min) increase in PTHrP mRNA by FA, associated with a perinuclear relocalization of Ang II/AT1 receptor, was inhibited by losartan but not candesartan, which traps Ang II receptors at the cell surface. Maximal PTHrP protein overexpression by FA (at 24 to 72 h)-or by exogenous Ang II-was abolished by both Ang II antagonists. PTHrP upregulation by FA was preceded by increased extracellular signal-regulated kinase (ERK) phosphorylation and inhibited by the ERK inhibitor PD098059. FA also activated cAMP response element-binding (CREB) protein, and this was prevented by losartan in these cells. Moreover, PTHrP mRNA overexpression by either FA or Ang II occurred in NRK 52E that were transfected with a CREB construct but not the dominant-negative CREB133 construct. These findings demonstrate that the decreased renal function and PTHrP overexpression in nephrotoxin-damaged kidney depends on renin-angiotensin system. In this setting, intracellular Ang II/AT1 receptor recycling seems to be related to PTHrP induction through ERK and CREB activation in tubuloepithelial cells.
Aortoduodenal fistula secondary to metastatic carcinoma. Angiographic demonstration
Authors: S. R. Geary
Journal: JAMA (1976)

AORTODUODENAL fistula is an uncommon but well-recognized pathologic entity. The majority of cases are caused by rupture of an aortic aneurysm or are complications of aortic reconstructive surgery. Carcinoma, either primary or metastatic, is a distinctly unusual cause. Because of the lesion's infrequency and its accompanying grave clinical condition, few patients with gastrointestinal hemorrhage caused by aortoduodenal fistula have been studied angiographically. The following is a case in which the fistula and its cause were detected by angiography. <h3>Report of a Case</h3> A 36-year-old woman had an exophytic lesion of the uterine cervix in September 1971. Results of a physical examination were otherwise normal. Hemogram, liver chemistry values, chest x-ray film, intravenous urogram, barium enema examination, sigmoidoscopy, and cystoscopy were normal. A biopsy specimen showed invasive, well-differentiated carcinoma, representing stage IB tumor. The patient received 4,000 rads of external radiation to the pelvis, followed by brief readmissions for intracavitary radiation
Angiopoietin-1 promotes endothelial cell proliferation and migration through AP-1–dependent autocrine production of interleukin-8
Authors: Nelly A. Abdel-Malak, Coimbatore B. Srikant, Arnold S. Kristof, Sheldon A. Magder, John A. Di Battista, Sabah N. A. Hussain
Journal: Blood (2008)
Tumors and DNA adducts in mice exposed to benzo[a]pyrene and coal tars: implications for risk assessment.
Authors: L S Goldstein, E H Weyand, S Safe, M Steinberg, S J Culp, D W Gaylor, F A Beland, L V Rodriguez
Journal: Environmental Health Perspectives (1998)

Current methods to estimate the quantitative cancer risk of complex mixtures of polycyclic aromatic hydrocarbons (PAH) such as coal tar assume that overall potency can be derived from knowledge of the concentration of a few carcinogenic components such as benzo[a]pyrene (B[a]P). Genotoxic damage, such as DNA adducts, is thought to be an essential aspect of PAH-induced tumorigenesis and could be a biomarker for exposure useful for estimating risk. However, the role of B[a]P and the relationship of adduct formation in tumorigenesis have not been tested rigorously in models appropriate for human health risk assessment. Therefore, we directly compared tumor induction and adduct formation by B[a]P and coal tars in several experimental protocols, including one broadly accepted and used by regulators. We found that B[a]P content did not account for tumor incidences after exposure to coal tars. DNA adducts were found in both tumors and tumor-free tissue and tumor outcomes were not predicted by either quantitation of total DNA adducts or by the DNA adduct formed by B[a]P. These data suggest that risk assessments based on B[a]P content may not predict accurately risk to human health posed by environmental PAH.
Serum Reagins and Leucocyte Response in Patients with House-dust Mite Allergy
Authors: E. S. K. Assem, M. K. McAllen
Journal: BMJ (1970)

A study was carried out on 26 patients with respiratory allergy due to the house-dust mite <i>Dermatophagoides pteronyssinus</i> and on 10 non-allergic control subjects using two in-vitro histamine release tests for assessing immediate-type allergy. The first test was on the patients9 serum and assessed reaginic (anaphylactic; possibly IgE) antibodies by passive sensitization of normal human lung tissue. The second test was on the patients9 leucocytes directly challenged with the mite antigen. Positive results were obtained in over 90% of patients, whereas the tests were either negative or very weakly positive in the control subjects. A significant degree of correlation was found between the two tests used, but pronounced differences were observed in a few instances. Confirmation of the role of IgE in tissue sensitization was obtained from tests with anti-IgE serum on leucocytes. Positive reactions of patients9 leucocytes were also obtained with anti-IgG, anti-IgA, and anti-IgM sera, which would suggest that antibodies belonging to these immunoglobulin classes may also play a part in immediate-type allergic reactions.