tbuckley/cabot-search huggingface dataset:
Interaction of baseline characteristics with the hazard of encainide, flecainide, and moricizine therapy in patients with myocardial infarction. A possible explanation for increased mortality in the Cardiac Arrhythmia Suppression Trial (CAST).
Authors: J L Anderson, E V Platia, A Hallstrom, R W Henthorn, T A Buckingham, M D Carlson, P E Carson
Journal: Circulation (1994)

BACKGROUND The Cardiac Arrhythmia Suppression Trial (CAST) was designed to test the hypothesis that suppression of ventricular ectopy with antiarrhythmic drugs after a myocardial infarction reduces the incidence of sudden arrhythmic death. Patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The encainide and flecainide arms of the study were discontinued in 1989 (CAST-I) and the moricizine arm in 1991 (CAST-II) because of excess mortality. To explore the mechanisms of these adverse outcomes, we examined the interaction of baseline characteristics with the hazard of therapy with encainide, flecainide, or moricizine compared with their respective placebos. METHODS AND RESULTS CAST-I comprised 755 patients assigned to flecainide or encainide and 743 patients assigned to placebo, whereas in CAST-II, 502 patients received moricizine and 491 patients received placebo. Clinical and laboratory baseline variables of patients receiving active drug and those receiving placebo were similar. In CAST-I patients, there was a significant interaction of active therapy with both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest for non-Q-wave myocardial infarction (total mortality hazard ratios, 1.8 versus 7.9 for Q-wave versus non-Q-wave infarction, P = .03). Ventricular premature depolarization (VPD) frequency &gt; or = 50/h and heart rate &gt; or = 74 beats per minute each interacted significantly with total mortality/cardiac arrest only. In the sicker CAST-II patients (ejection fraction &lt; or = 40%), only diuretic use at baseline interacted significantly with moricizine use for both all-cause death/cardiac arrest and arrhythmic death/cardiac arrest (total mortality hazard ratios, 1.9 versus 0.7 for diuretic use versus no use, P = .01). CONCLUSIONS Although active treatment in CAST-I was associated with greater mortality than placebo with respect to almost all baseline variables, the therapeutic hazard was more than expected in patients with non-Q-wave myocardial infarction and (for total mortality) frequent premature VPDs and higher heart rates, suggesting that the adverse effect of encainide or flecainide therapy is greater when ischemic and electrical instability are present. The relative hazard of therapy with moricizine in the sicker CAST-II population was greater in those using diuretics. Thus, although these drugs have the common ability to suppress ventricular ectopy after myocardial infarction, their detrimental effects on survival may be mediated by different mechanisms in different populations, emphasizing the complex, poorly understood hazards associated with antiarrhythmic drug treatment.
Death from cancer at home: the carers' perspective.
Authors: R V Jones, J Hansford, J Fiske
Journal: BMJ (1993)

OBJECTIVES--To collect information from principal carers of people who had died at home with cancer; to identify areas of support which need improvement. DESIGN--Semistructured interviews with carers two to four months after the death. SETTING--38 general practices in the Exeter, Torbay, and Plymouth health districts. SUBJECTS--207 carers. MAIN OUTCOME MEASURES--Services received by carers and quality of support. RESULTS--161 of 207 patients were aged 60 or over. 88 carers were aged under 60, 110 were 60-80, and 9 were &gt; 80. Carers had difficulty in getting urgent professional help in only 15 out of 177 cases. 124 carers were not given advice on financial help and 174 were not told of support available from local charities. Although pain was well controlled, 25% of patients had no relief of other symptoms. Overall, 150 carers considered the support excellent, 45 good, 8 moderate, 2 poor, and 2 had no comment. CONCLUSIONS--Although care has improved in recent years, health professionals need to give carers more advice about help available outside health services. Domestic help was often needed earlier. Better appreciation of carers9 problems is needed.
Laryngeal leiomyosarcoma in a patient with Sezary syndrome
Authors: S. Ingen-housz-Oro, H. Bachelez, J. Mikol, M. Viguier, P. Marandas, L. Dubertret
Journal: British Journal of Dermatology (2002)

Sir, Sézary syndrome (SS) is the leukaemic form of epidemotropic cutaneous T‐cell lymphoma (CTCL) characterized by pruritus and squamous erythroderma. Secondary malignancies, mostly cutaneous and internal carcinomas, have been reported in patients with SS.1 On the other hand, leiomyosarcomas have been reported in immunocompromised patients.2 We report herein a case of laryngeal leiomyosarcoma in a patient with SS. As previous studies pointed to the possible relationship between leiomyosarcoma in immunocompromised patients and the Epstein–Barr virus (EBV), we investigated for the presence of EBV in the development of the laryngeal tumour. A 78‐year‐old man was referred in September 2000 for a generalized pruritus following a chronic course of 6 years' duration. The patient had previously received topical corticosteroids and UVA–UVB phototherapy without improvement of skin symptoms. In 1998, the diagnosis of SS was established upon considering the results of a skin biopsy and the presence of circulating large Sézary cells. The patient was treated with chlorambucil from April 1998 to December 1999, resulting in a transient, partial remission of the pruritus. Alternative regimens with methotrexate and acitretin had no effect.
George Washington and Variolation; Edward Jenner and Vaccination
Authors: Rafael Rabasa
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In the Aug 23/30, 1985, issue ofThe Journal, an advertisement with the heading "Army Medicine Has Been Winning Battles for Two Centuries"<sup>1</sup>states that General George Washington ordered smallpox inoculation of the Continental Army in 1777. This statement is not true. In 1777, there was no smallpox vaccine available. In May 1796, Edward Jenner found a young dairymaid, Sarah Nelmes, with fresh cowpox lesions on her fingers. On May 14, using matter from Sarah's lesions, he inoculated an 8-year-old boy, James Phipps. On July 1, Jenner inoculated the boy again, this time with smallpox matter, protection was complete, and no disease developed. General George Washington could not have possibly ordered the smallpox inoculation 19 years before the discovery of the vaccine.
Alcohol Withdrawal and Noradrenergic Function
Authors: MARKKU LINNOILA
Journal: Annals of Internal Medicine (1987)

Alcohol withdrawal syndrome is characterized by signs of overactivity of the sympathetic nervous system. Biochemical studies indicate that increased release of norepinephrine is associated with certain symptoms of alcohol withdrawal, and the severity of the withdrawal symptoms correlates positively with the amount of norepinephrine released. In the rat, the brain epinephrine concentration is reduced by alcohol, a phenomenon probably associated with both the intoxicating and rewarding effects of alcohol intake. Furthermore, intoxicating effects of alcohol can be reversed by inhibiting epinephrine synthesis in the rat brain. In this species, alcohol withdrawal is associated with profound depletion of epinephrine in the hypothalamus. When Clonidine, a norepinephrine alpha-2-receptor agonist, was infused in alcoholics, these receptors were found to be subsensitive during alcohol withdrawal, and this subsensitivity may contribute to the syndrome. Repeated withdrawals may lead to "kindling" and thus further enhancement of noradrenergic overactivity. Pituitary responsiveness to corticotropin-releasing hormone, which is a central regulator of stress responses and increases the firing rate of brain noradrenergic neurons, is altered during alcohol withdrawal.
Oncologists' Reply: Survival Expectancy in Acute Lymphocytic Leukemia
Authors: James F. Holland
Journal: New England Journal of Medicine (1972)

The editor of the Journal in a recent editorial,1 indicated that the Director of the National Cancer Institute "is said to have pointed out that 50 per cent of children with acute lymphocytic leukemia [who get] optimal treatment survive at least five years today. Tragically only 15 per cent of the children afflicted get optimal treatment." We believe our data indicate that 50 per cent of children now under optimal treatment as it is known today should survive for at least five years. With this qualification, the statement is defensible.The editor volunteered to print the directions for such treatment. . . .
Chief medical officer advises government to allow mitochondrial replacement to prevent disease
Authors: S. Mayor
Journal: BMJ (2013)

England’s chief medical officer is recommending that the UK government introduce regulations to enable couples at high risk of having a child with severe mitochondrial disease to undergo in vitro fertilisation (IVF) to replace the mother’s faulty mitochondria with those from a healthy donor.

The decision is likely to make the United Kingdom the first country in the world to provide mitochondrial replacement to prevent serious mitochondrial disease. The technique is considered controversial because it adds new DNA to the resulting embryo, by combining nuclear DNA from both parents with a tiny amount of mitochondrial DNA from a donor.

“This is not a decision to take lightly,” said the chief medical officer, Sally Davies. “There are clearly some sensitive issues here, but it is clear that, overall, there is general support for allowing these treatment techniques to be used, subject to strict safeguards.”

Her recommendation came …
Leveraging the Immune System during Chemotherapy: Moving Calreticulin to the Cell Surface Converts Apoptotic Death from “Silent” to Immunogenic
Authors: Michel Obeid, Theocharis Panaretakis, Antoine Tesniere, Nick Joza, Roberta Tufi, Lionel Apetoh, François Ghiringhelli, Laurence Zitvogel, Guido Kroemer
Journal: Cancer Research (2007)

Abstract In contrast to prior belief, tumor cell apoptosis is not necessarily silent but can be immunogenic. By tracing how anthracyclines and γ-irradiation trigger immunogenic cell deaths, we found that they were causally connected to the exposure of calreticulin on the tumor cell surface, before apoptosis in the tumor cell itself occurred. Furthermore, we showed that calreticulin exposure was necessary and sufficient to increase proimmunogenic killing by other chemotherapies. Our findings suggest that calreticulin could serve as a biomarker to predict therapy-associated immune responses, and that tactics to expose calreticulin might improve the clinical efficacy of many cancer therapies. [Cancer Res 2007;67(17):7941–4]
10 minute consultation: Chronic cough
Authors: Robert D Gray, John McKay, Graeme P Currie
Journal: BMJ (2003)

Graeme Currie and John McKay take you through a common consultation in primary care--patients with chronic cough A 42 year old woman presents with an eight month history of non-productive chronic cough. Her general health is good other than hypertension. She finds social situations embarrassing and is fed up as the cough causes urinary incontinence and disrupts her sleep.
Reversibility of Vasectomy
Authors: EUGENE V. CATTOLICA
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 September 1971Reversibility of VasectomyEUGENE V. CATTOLICA, M.D.EUGENE V. CATTOLICA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-3-475_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his timely editorial (Ann Intern Med73:853, 1970), Dr. Ziegler comments on vasectomy and adverse psychological reactions. He states that vasovasostomy can be successful in a very high percentage, "perhaps over 90%." This argument, he feels, is useful in minimizing the "psychological impact" of the procedure. It should be noted, however, that vasectomy is usually intended as a permanent sterilizing procedure by most vasectomists. The great variety of surgical procedures that have been described are testimony to the difficulty in surgically establishing a functioning vasovasostomy (1-8). Many technical factors relating to the methods of the initial...References1. O'CONOR V: Anastomosis of the vas deferens after purposeful division for sterility. J Urol 59:229-233, 1948 CrossrefMedlineGoogle Scholar2. ROLAND S: Splinted and non-splinted vasovasotomy. A review of the literature and a report of nine new cases. Fertil Steril 12:191-195, 1961 CrossrefMedlineGoogle Scholar3. MASSEY B and NATION E: Vas deferens anastomosis. A report of four consecutive successful cases. J Urol 61:391-395, 1949 CrossrefMedlineGoogle Scholar4. FREIBERS H and LEPSKY H: Restoration of the continuity of the vas deferens eight years after bilateral vasectomy. J Urol 41:934, 1939 CrossrefGoogle Scholar5. DORSEY J: Anastomosis of the vas deferens to correct postvasectomy sterility. J Urol 70:515-519, 1953 CrossrefMedlineGoogle Scholar6. CAMERON C: Anastomosis of the vas deferens. JAMA 127:1119-1120, 1945 CrossrefMedlineGoogle Scholar7. WALLER J and TURNER T: Anastomosis of the vas after vasectomy. J Urol 88:409-410, 1962 CrossrefMedlineGoogle Scholar8. FERNANDES M, SHAH K, and DRAPER J: Vasovasotomy: improved microsurgical technique. J Urol 100:763-766, 1968 CrossrefMedlineGoogle Scholar9. PHADKE G and PHADKE A: Experiences in the re-anastomosis of the vas deferens. J Urol 97:888-890, 1967 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: EUGENE V. CATTOLICA, M.D.Affiliations: 3006 Chestnut Hill Dr. Sacramento, Calif. 95826 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1971Volume 75, Issue 3Page: 475-475KeywordsAdverse reactionsVasectomy ePublished: 1 December 2008 Issue Published: 1 September 1971 PDF downloadLoading ...
Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one.
Authors: G J Kontoghiorghes, M A Aldouri, A V Hoffbrand, J Barr, B Wonke, T Kourouclaris, L Sheppard
Journal: BMJ (1987)

The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective doses suggest that it should be developed quickly and thoroughly tested for the management of transfusional iron overload.
Expression and Distribution of the Type 1 and Type 3 Inositol 1,4,5-Trisphosphate Receptor in Developing Vascular Smooth Muscle
Authors: Paul N. Tasker, Francesco Michelangeli, Graeme F. Nixon
Journal: Circulation Research (1999)

Abstract —The recent discoveries of inositol 1,4,5-trisphosphate (IP 3 ) receptor subtypes with different affinities for IP 3 and their potential involvement in development has important consequences for vascular smooth muscle. This study has examined the expression and distribution of the type 1 and type 3 IP 3 receptor subtypes in developing rat vascular smooth muscles. Immunoblotting of portal vein and aorta from neonatal (2 to 4 days) and fully developed (6 weeks) rats revealed significantly higher levels of the type 3 IP 3 receptor expression in neonatal, compared with developed, vascular smooth muscles. In contrast, expression of the type 1 IP 3 receptor in neonates was lower compared with developed vascular smooth muscles. Immunolocalization of the type 3 IP 3 receptors in neonatal tissues revealed that staining corresponded to the distribution of the sarcoplasmic reticulum (visualized by osmium ferricyanide staining of thin tissue sections), which suggested localization of the type 3 IP 3 receptor throughout the sarcoplasmic reticulum network. We conclude that type 3 IP 3 receptors are the predominant subtype in the development of vascular smooth muscle and are distributed throughout the sarcoplasmic reticulum in these cells. The switch in isoforms of the IP 3 receptor during development from the type 3 with low affinity for IP 3 to the higher-affinity type 1 receptor may play a role in calcium-mediated regulation of developing vascular smooth muscle.
The Increasing Rate of Suicide by Firearms
Authors: Jeffrey H. Boyd
Journal: New England Journal of Medicine (1983)

The rate of suicide has risen over the past 25 years, particularly among persons under the age of 40 years. An examination of types of suicide shows that only the rate of suicide by means of firearms has risen continuously over this period. From 1953 to 1978, the age-adjusted rate of suicide by means of firearms increased from 4.9 to 7.1 per 100,000 population per year, whereas the age-adjusted rate of suicide by all other means remained the same: 5.9 in 1953 and 5.4 in 1978. I have examined and rejected the hypothesis that this striking increase in suicide by firearms could have been due to an increase in self-inflicted firearm accidents that were misdiagnosed as suicide. It is conceivable that the rise in the suicide rate might be controlled by restricting the sale of handguns, since another study has shown that handguns account for 83 per cent of all suicides by firearms.
Assessment of Coronary Artery Disease by Cardiac Computed Tomography
Authors: Matthew J. Budoff, Stephan Achenbach, Roger S. Blumenthal, J. Jeffrey Carr, Jonathan G. Goldin, Philip Greenland, Alan D. Guerci, Joao A.C. Lima, Daniel J. Rader, Geoffrey D. Rubin, Leslee J. Shaw, Susan E. Wiegers
Journal: Circulation (2006)
Professor warns of "brain drain" of diabetes researchers from Europe
Authors: C. Kovac
Journal: BMJ (2002)

Europe stands to lose many highly qualified diabetes researchers if governments fail to earmark more money to fund studies, says a leading diabetes specialist.

The remarks were made by Professor Philippe Halban, president of the European Association for the Study of Diabetes, during its annual meeting last week in Budapest. The meeting was attended by some 11 000 doctors and scientists from 113 countries.

An estimated 200 million people worldwide— 10 million of them in Europe— have diabetes and its associated complications. These figures are expected to double by 2025. …
Paul Michael Anthony Bowden
Authors: S. Wilson
Journal: BMJ (2014)

Paul Michael Anthony Bowden was sent to Coventry for a year by the prison officers at Brixton. Born the third of five boys, in Stoke on Trent, he survived an education from the Christian Brothers and left with a determination to alleviate suffering, particularly at the hands of institutions, and he was the Home Office psychiatrist at Brixton for many years. The foremost forensic psychiatrist of his generation, working at what was then the main remand prison for London, he gave expert psychiatric evidence in many high profile cases. Renowned for his clarity and brevity …
Evidence for the significant role of immunoglobulin light chains in antigen recognition and selection in chronic lymphocytic leukemia
Authors: Anastasia Hadzidimitriou, Nikos Darzentas, Fiona Murray, Tanja Smilevska, Eleni Arvaniti, Cristina Tresoldi, Athanasios Tsaftaris, Nikolaos Laoutaris, Achilles Anagnostopoulos, Frederic Davi, Paolo Ghia, Richard Rosenquist, Kostas Stamatopoulos, Chrysoula Belessi
Journal: Blood (2008)
SERUM-THERAPY IN TUBERCULOSIS.
Authors: W. THORNTON PARKER
Journal: JAMA (1899)

A recent paper by Dr. Robert Reyburn, at the meeting of theAmerican Medical Association(videJournal, Oct. 1, 1898) has attracted my attention as being an excellent illustration of the best thought on this perplexing subject, and I wish to call attention to some points which are particularly useful to remember when we are considering the question of the treatment of tuberculosis. After quoting Hirsch as stating that ''about one-seventh of the mortality that exists among civilized men is due to tuberculosis,'' the inquiry is made: ''What are the principles of treatment that should guide the physician in the management of cases of tuberculosis?'' That tuberculosis can be cured Dr. Reyburn, with many others, firmly believes. ''That these cases are cured is proven by the universally admitted fact that a large proportion of cadavers of persons who have died from many different diseases have, on postmortem examination, shown indubitable
Simultaneous inhibition of metastasis and growth of breast cancer by co-delivery of twist shRNA and paclitaxel using pluronic P85-PEI/TPGS complex nanoparticles
Authors: Jianan Shen, Huiping Sun, Pengfei Xu, Qi Yin, Zhiwen Zhang, Siling Wang, Haijun Yu, Yaping Li
Journal: Biomaterials (2012)