tbuckley/cabot-search huggingface dataset:
AMA Specialty Journals— Thorn or Diadem?
Authors: Richard Warren
Journal: JAMA (1976)

To the Editor.—  Individuals have no monopoly on split personalities. We find them also in organized groups. The American Medical Association is an example of such organizational schizophrenia. One half of its personality is that of a trade guild, which protects for its members their freedom of mobility and financial autonomy; the other is that of the service organization, which protects the public by using professional know-how for education and the setting of standards for practice and health services. The ebb and flow of the struggle between these two halves have, until recent years, left the AMA's specialty journals relatively untouched. But times have changed, and the journals have been in an upheaval.  Since the autumn of 1972, we have seen (1) an announcement to eliminate nonpaid subscriptions and retraction thereof (223:76, 1973), (2) a new chief editor come and then resign on the basis of disagreement on priorities for
668 HCV INDUCES ACUTE AND CHRONIC ENDOPLASMIC RETICULUM (ER) STRESS, CAUSING ADAPTATION AND RESISTANCE TO ER STRESS INDUCED APOPTOSIS: A POSSIBLE VIRAL EVASION MECHANISM
Authors: E. Merquiol, S. Mezan, M. Mills, B. Tirosh, O. Shibolet
Journal: Journal of Hepatology (2010)
Studies on human plasma C1 inactivator-enzyme interactions. I. Mechanisms of interaction with C1s, plasmin, and trypsin.
Authors: P C Harpel, N R Cooper
Journal: Journal of Clinical Investigation (1975)

This study has explored the nature of the molecular events which occur when C1 inactivator, a human plasma inhibitor of the complement, kinin-forming, coagulation, and fibrinolytic enzyme systems, interacts with C1s, plasmin, and trypsin. Purified inhibitor preparations demonstrated two bands, when examined by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS). The molecular weights of the major and minor bands were 105,000 and 96,000 daltons, respectively. The minor component appeared to be immunologically and functionally identical to the main C1 inactivator component. Loss of C1s and plasmin functional activity was associated with the formation of a 1:1 molar complex between the inhibitor and each enzyme. These complexes were stable in the presence of SDS and urea. The light chain of both these enzymes provided the binding site for C1 inactivator. Complex formation and enzyme inhibition occurred only with native and not with an inhibitor preparation denatured by acid treatment, thereby demonstrating the importance of conformational factors in the enzyme-inhibitor reaction. Although peptide bond cleavage of the C1 inactivator molecule by C1s was not documented, plasmin was found to degrade the inhibitor with the production of several characteristic derivatives. At least one of these products retained the ability to complex with C1s and plasmin. Trypsin, which failed to form a complex with C1 inactivator, degraded the inhibitor in a limited and sequential manner with the production of nonfunctional derivatives one of which appeared structurally similar to a plasmin-induced product. These studies therefore, provide new information concerning the molecular interactions between C1 inactivator and several of the proteases which it inhibits.
Regulations on sharing concerns about doctors are like "gossips' charter"
Authors: C. Dyer
Journal: BMJ (2010)

“Flawed” regulations that put employers and other designated bodies under a duty to share concerns about doctors’ performance and conduct could give rise to legal challenge and breach doctors’ human rights, says the Medical Defence Union (MDU).

The regulations under the Health and Social Care Act 2008, which are due to come into force in October 2010, follow concern that the lack of “joined up” information can allow incompetent or abusive doctors to go on practising for years.

Failure to pass on information was identified as a factor in the long career of Harold Shipman, the GP thought to have murdered at least 250 patients over 20 years. It was also highlighted in inquiries into the activities of Clifford Ayling, a GP, and William Kerr and Michael Haslam, two consultant psychiatrists—all of whom sexually abused patients over many …
A Case of Scurvy
Authors: A. E. Barnes
Journal: BMJ (1947)

MEDICAL MEMORANDABRMEisLO rough and wrinkled.On nutrient agar, button-like colonies, with flat rims and central crater-like depressions, developed.Growth on 5% glycerin agar was first of the mucoid type, but after four days developed the typical corruigated form of Pfeifgerella whitmori.Fermented lactose, glucose, mannite, dulcite, and dextrin, with production of acid but no gas.Liquefied gelatin.Milk clotted in four days.Indole-negative.Animal Inoculation.-Anadult male guinea-pig inoculated intraperitoneally with 0.1 ml. of a faintly opalescent saline suspension of the organism developed the typical ' Strauss "' reaction after 36 hours and died in 48 hours.Post-mortem examination of the animal disclosed both testes swollen and haemorrhagic, and some turbid fluid in the sac of the tunica vaginalis.Numerous miliary nodules were observed in the spleen, in the omentuim, on the peritoneal surface of the bowel, and in the lungs.There was a large amount of free turbid fluid in the peritoneal cavity.The organism was recovered in pure culture from the heart's blood and from the lesions in the spleen.
Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon α
Authors: K Merx, MC Müller, S Kreil, T Lahaye, P Paschka, C Schoch, A Weisser, C Kuhn, U Berger, H Gschaidmeier, R Hehlmann, A Hochhaus
Journal: Leukemia (2002)
Loss of nocturnal decline in blood pressure after cardiac transplantation.
Authors: R A Reeves, A P Shapiro, M E Thompson, A M Johnsen
Journal: Circulation (1986)

Twenty-four hour noninvasive ambulatory blood pressure and heart rate monitoring was performed on patients who underwent orthotopic cardiac transplantation, as part of the investigation of the de novo hypertension that developes in such patients. Patients with essential hypertension served as control subjects. The results demonstrated a highly significant loss of the usual decline in blood pressure and heart rate during sleep in the transplant patients. A similar loss of nocturnal decline in blood pressure was noted in a group of 10 patients with autonomic neuropathy secondary to diabetes mellitus. The de novo hypertension associated with cardiac transplantation is probably multicausal. Impairment of renal function by cyclosporin-A with associated salt and water retention and persistent elevation of the systemic vascular resistance in the presence of a restored normal cardiac output by the "new" heart are major factors. In addition, loss of the normal nocturnal decline in blood pressure and heart rate, which probably is related to the denervated state of the transplanted heart, may play an important role in blood pressure control.
Variation and heritability of Hb F and F‐cells among β‐thalassemia heterozygotes in Hong Kong
Authors: Geoffrey T. Gibney, Carolien I.M. Panhuysen, Jason C.C. So, Edmond S.K. Ma, Shau Yin Ha, Chi Kong Li, Anselm C.W. Lee, Chi Keung Li, Hui Leung Yuen, Yu Lung Lau, David M. Johnson, John J. Farrell, Alice B. Bisbee, Lindsay A. Farrer, Martin H. Steinberg, Li Chong Chan, David H.K. Chui
Journal: American Journal of Hematology (2008)

Abstract Enhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with β‐thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult β‐thalassemia carriers in Hong Kong. They had wide variations in Hb F and F‐cell numbers skewing toward higher levels. Individuals who coinherited the Xmn I T‐allele in the G γ‐globin gene promoter had higher Hb F and more F‐cells compared with those lacking the Xmn I T‐allele. However, both groups exhibited a similarly wide spread of Hb F and F‐cells. The correlation of Hb F and F‐cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F‐cells were calculated in 66 families (111 parents who were β‐thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F‐cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Eosinophilic "empyema" associated with crack cocaine use
Authors: D H Strong
Journal: Thorax (2003)

Smoking of crystalline cocaine, known as "crack" cocaine, has been associated with eosinophilic pneumonitis, but not with pleural effusions. We describe a patient with eosinophilic pneumonitis with an eosinophilic "empyema" after using "crack" cocaine. The illness resolved with corticosteroids. We hypothesised that his effusion would have increased levels of eosinophil cytokines that promote oedema, and found a marked increase in pleural vascular endothelial growth factor (VEGF) and smaller increases in interleukins IL-5, IL-6, and IL-8. In the setting of "crack" use, we suggest that a pleural effusion that appears grossly to be pus should be evaluated for eosinophilic inflammation. Such eosinophilic effusions may respond to corticosteroids alone, consistent with a non-infectious process driven by proinflammatory cytokines.
Molecular Pathways: CDK4 Inhibitors for Cancer Therapy
Authors: Mark A. Dickson
Journal: Clinical Cancer Research (2014)

Unrestrained growth is the hallmark of cancer, and disrupted cell-cycle regulation is, therefore, common. CDK4 is the key regulator of the G1-S transition. In complex with cyclin D, CDK4 phosphorylates retinoblastoma protein (Rb) and drives cell-cycle progression, a process inhibited by p16. The p16-CDK4-cyclin D-Rb is aberrant in the majority of cancers and is, thus, a logical target for anticancer therapy. Previous attempts to block CDK4 with nonselective cyclin-dependent kinase (CDK) inhibitors led to toxicity and little efficacy. However, the recent development of selective CDK4 inhibitors launched the first successful efforts to target the pathway for cancer therapy. Three oral selective CDK4 inhibitors have entered clinical trials: palbociclib (PD0332991), LEE011, and LY2835219. CDK4 inhibitors have in vitro activity against a broad range of cancers and in patients have shown antitumor activity in breast cancer, lymphoma, sarcoma, and other tumors. Major efforts are under way to develop biomarkers of response, understand potential mechanisms of resistance, and develop rational combinations of CDK4 inhibitors with chemotherapy and other targeted drugs.
Missed Torsion in Undescended Testes Detected by Scintigraphy
Authors: Sunil Kumar Kodali, Zuhair Saleh Abdullah, Punit Sharma, Muhammad Umar Khan, Muhammad Naeem
Journal: Clinical Nuclear Medicine (2012)

Torsion of undescended testis, although not uncommon, causes diagnostic difficulties. We here present testicular scintigraphy images of a typical case of torsion of an undescended inguinal testis with disparity between clinical and ultrasonography (USG) findings in the contralateral retractile testis.
Phylogenetic Estimation of Context-Dependent Substitution Rates by Maximum Likelihood
Authors: A. Siepel
Journal: Molecular Biology and Evolution (2003)

Nucleotide substitution in both coding and noncoding regions is context-dependent, in the sense that substitution rates depend on the identity of neighboring bases. Context-dependent substitution has been modeled in the case of two sequences and an unrooted phylogenetic tree, but it has only been accommodated in limited ways with more general phylogenies. In this article, extensions are presented to standard phylogenetic models that allow for better handling of context-dependent substitution, yet still permit exact inference at reasonable computational cost. The new models improve goodness of fit substantially for both coding and noncoding data. Considering context dependence leads to much larger improvements than does using a richer substitution model or allowing for rate variation across sites, under the assumption of site independence. The observed improvements appear to derive from three separate properties of the models: their explicit characterization of context-dependent substitution within N-tuples of adjacent sites, their ability to accommodate overlapping N-tuples, and their rich parameterization of the substitution process. Parameter estimation is accomplished using an expectation maximization algorithm, with a quasi-Newton algorithm for the maximization step; this approach is shown to be preferable to ordinary Newton methods for parameter-rich models. Overlapping tuples are efficiently handled by assuming Markov dependence of the observed bases at each site on those at the N − 1 preceding sites, and the required conditional probabilities are computed with an extension of Felsenstein's algorithm. Estimated substitution rates based on a data set of about 160,000 noncoding sites in mammalian genomes indicate a pronounced CpG effect, but they also suggest a complex overall pattern of context-dependent substitution, comprising a variety of subtle effects. Estimates based on about 3 million sites in coding regions demonstrate that amino acid substitution rates can be learned at the nucleotide level, and suggest that context effects across codon boundaries are significant.
Marked Peripheral Edema Associated with Montelukast and Prednisone
Authors: Mario Geller
Journal: Annals of Internal Medicine (2000)

Letters6 June 2000Marked Peripheral Edema Associated with Montelukast and PrednisoneMario Geller, MDMario Geller, MDRua Visconde de Pirajá; 22410-001 Rio de Janeiro, Brazil (Geller)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-11-200006060-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Cysteinyl leukotriene-receptor antagonists are new drugs for the treatment of persistent asthma (1). They may be used as alternatives to corticosteroids or adjuncts to corticosteroids in some patients with asthma. They are available orally and provide safe and effective therapy as long as compliance is good (2).A 23-year-old man with persistent severe perennial allergic asthma and rhinoconjunctivitis was evaluated for acute respiratory symptoms. He also had exercise-induced asthma and was sensitive to house dust mites, Dermatophagoides pteronyssinus, D. farinae, and Blomia tropicalis. From age 1 to 7 years, he had minimal-change nephrotic syndrome that completely resolved ...References1. Drazen JM, Israel E, O'Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med. 1999;340:197-206. CrossrefMedlineGoogle Scholar2. Busse W. The role and contribution of leukotrienes in asthma. Ann Allergy Asthma Immunol. 1998;81:17-26. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Mario Geller, MDAffiliations: Rua Visconde de Pirajá; 22410-001 Rio de Janeiro, Brazil (Geller) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMontelukast medicines of today and tomorrow: from molecular pharmaceutics to technological formulationsMontelukast-induced metamorphopsia in a pediatric patientCorticosteroids—glucocorticoidsCORTICOSTEROIDS AND PROSTAGLANDINSGLUCOCORTICOIDS AND DISEASE – MODIFYING ANTIRHEUMATIC DRUGSCORTICOSTEROIDS AND RELATED DRUGSCorticosteroids—glucocorticoidsCorticotrophins, corticosteroids, and prostaglandinsPrednisone interaction 6 June 2000Volume 132, Issue 11Page: 924KeywordsAsthmaDrugsEdemaMitesPatientsPropionatesProteinsSodiumThoraxUrine ePublished: 15 August 2000 Issue Published: 6 June 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Predictors of stroke after conventional versus coronary revascularization without cardiopulmonary bypass
Authors: Sotiris C. Stamou, Albert J. Pfister, Kathleen A. Jablonski, Peter C. Hill, Mercedes K. Dullum, Ammar S. Bati, Steven W. Boyce, Kathleen Petro, Paul J. Corso
Journal: Journal of the American College of Cardiology (2002)
Frequency of Prenatal Care Visits and Perinatal Outcome
Authors: Richard W. Zalar
Journal: JAMA (1996)

To the Editor.  —Dr McDuffie and colleagues1have met all the requirements of good science in their study of the effect of the frequency of prenatal care visits on perinatal outcome among low-risk women. I have several criticisms of this study, however. First, the catalog of maternal outcomes includes some that could not possibly be affected by any kind of prenatal care: multiple gestation, placenta previa, abruptio placentae, postpartum hemorrhage. Why include these?  Second, our goal in obstetrics should be excellence, not mediocrity. A stillbirth rate of 4 per 1000 is not particularly good in an already low-risk group of patients. We should not seek to see how few visits can preserve the average outcome. If efficiency is the issue, the question should be how few visits can preserve the best outcome. Similarly, the preterm and low-birth-weight rates are unimpressive in this low-risk group of insured patients. Although standard
Alcohol and Congestive Heart Failure
Authors: Craig R. Walsh, Daniel Levy
Journal: Annals of Internal Medicine (2003)

Letters7 January 2003Alcohol and Congestive Heart FailureCraig R. Walsh, MD and Daniel Levy, MDCraig R. Walsh, MDFramingham Heart Study, Framingham, MA 01702 (Walsh, Levy)Search for more papers by this author and Daniel Levy, MDFramingham Heart Study, Framingham, MA 01702 (Walsh, Levy)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-138-1-200301070-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Dong raises interesting questions about the influence of genetic variation in alcohol metabolism on the association between alcohol consumption and risk for congestive heart failure. Polymorphisms of the ADH2 and ALDH2 genes are relatively uncommon in populations of white ethnicity (1) and are therefore unlikely to substantially affect the association between alcohol consumption and congestive heart failure in our study, which was conducted in a largely white sample. Caution is warranted in extrapolating our findings to nonwhite populations in which polymorphisms of ADH2 and ALDH2 are common.As Dr. Dong correctly points out, genetic polymorphisms of the ...References1. Bosron WF, Lumeng L, Li TK. Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. Mol Aspects Med. 1988;10:147-58. [PMID: 3067025] CrossrefMedlineGoogle Scholar2. Hines LM, Stampfer MJ, Ma J, Gaziano JM, Ridker PM, Hankinson SE, . Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med. 2001;344:549-55. [PMID: 11207350] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Craig R. Walsh, MD; Daniel Levy, MDAffiliations: Framingham Heart Study, Framingham, MA 01702 (Walsh, Levy) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAlcohol Consumption and Risk for Congestive Heart Failure in the Framingham Heart Study Craig R. Walsh , Martin G. Larson , Jane C. Evans , Luc Djousse , R. Curtis Ellison , Ramachandran S. Vasan , and Daniel Levy Alcohol and Congestive Heart Failure XinQi Dong Metrics 7 January 2003Volume 138, Issue 1Page: 75-76KeywordsAlcohol consumptionAlcoholsGenetic polymorphismGeneticsHeart failureHigh density lipoprotein cholesterolLongitudinal studiesMyocardial infarctionPopulation statisticsRacial and ethnic issues ePublished: 7 January 2003 Issue Published: 7 January 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comparison of medical treatment with percutaneous closure of patent foremen ovale for secondary prevention of TIAs and strokes: a case-control study
Authors: Stephan Windecker, Andreas Wahl, Markus Schwerzmann, Christian Seiler, Krassen Nedeltchev, Marcel Arnold, Matthias Sturzenegger, Heinrich Mattle, Bernhard Meier
Journal: Journal of the American College of Cardiology (2002)
Deaths from stroke in younger people.
Authors: C Wolfe
Journal: BMJ (1993)

cells in the epidermis to express the high affinity IgE receptor'7 and do so especially in atopic eczema,18 in which IgE may play a part in antigen presentation.'9These strands of information still have to be woven into a coherent theory, and it remains likely that many genes and environmental factors play a part in the pathogenesis of atopic diseases.Nevertheless, at last a bridge is being built between the immediate hypersensitivity components of atopy, such as asthma and hay fever, and the delayed ones, such as eczema.We must wait for the next instalment of this still shadowy but important story.Meanwhile, the prevalence of atopy continues to rise.
Aspirin Preparations and Their Noxious Effect on the Gastro-intestinal Tract
Authors: L. Th. F. L. Stubbe, J. H. Pietersen, C. Van Heulen
Journal: BMJ (1962)

A solution of aspirin is as potent a cause of blood loss as the B.P. tablet of aspirin.This suggests that undissolved tablet particles have no direct relevance to this problem.It is suggested that gastric absorption of undissociated acetylsalicylic acid is one of the factors concerned in causing blood loss.This leads us to question the validity of much prevailing thought about physico-chemical differences between different preparations of aspirin.We are indebted to Dr. B. K. Martin for much help and advice; to Mr. M. P. Curwen for advice on the statistical treatment of the results; to Mrs. E. B.
Common paediatric problems
Authors: A R Prem
Journal: BMJ (2006)

Common paediatric problems A R PremMany paediatric problems can present to medical professionals.This article covers some of the common ones including phimosis, undescended testis, retractile testis, vesicoureteric junction reflex, hypospadias, neonatal hydronephrosis, obstruction of the pelviureteric junction, and some types of tumour. PhimosisPhimosis is the most common reason for circumcision, although recurrent balanitis is also an indication.Circumcision may also be performed for religious or social reasons.At birth, adhesions are present between the glans penis and foreskin, but separation begins to occur immediately and continues thereafter.The prepuce normally becomes retractile after the age of two years, but many adolescent boys retain some adhesions.Preputial adhesions are a common reason for referral to a urologist, but adhesions are normal and should be treated only if "physiological phimosis" persists into adolescence and causes problems with masturbation or sexual intercourse.A non-retractile foreskin is free of symptoms and self limiting, and circumcision is not needed.Parents often say that the prepuce "balloons" when the child urinates, but this is a sign of a non-retractile foreskin rather than phimosis.Careful examination will show that the urethral meatus is visible through the narrowed preputial opening, and, with time, this opening widens to allow the foreskin to retract normally.True or "pathological phimosis" is rare, but it may cause appreciable problems in childhood or adolescence.Treatment is usually circumcision, whereas alternative treatments are preputioplasty or application of steroid creams.