tbuckley/cabot-search huggingface dataset:
Anybody else for warfarin?
Authors: James Owen Drife
Journal: BMJ (2012)

Lymphocyte cytotoxicity for isolated hepatocytes has been demonstrated in 93% of cases of acute viral hepatitis tested within two weeks of the onset of symptoms. The frequency of cytotoxicity during this time was similar for HBsAg positive and negative cases. However, after this time it was significantly higher in HBsAg positive than negative cases, 90% and 25% respectively (P less than 0-01). Cytotoxicity was found in B-cell, but not T-cell, enriched fractions of lymphocytes, compatible with an antibody-dependent K-cell mediated reaction. In two cases the assay remained positive on retesting six months later, and follow-up liver biopsies showed the features of chronic aggressive hepatitis. These findings suggest that, in addition to the known immunological reactions against viral antigens that occur during the acute phase of viral hepatitis, an autoimmune reaction directed against a liver specific protein is also initiated; and if this reaction persists then chronic hepatitis may develop.
Management of infertility
Authors: Adam H Balen, Anthony J Rutherford
Journal: BMJ (2007)

#### Summary points Around 9% of couples are involuntarily childless. At least a quarter of couples experience unexpected delays in achieving their desired family size,1 although only a half seek treatment. In recent years, publicity about infertility treatments has increased, and couples are now more willing to seek advice. The first of these two brief reviews covers the main causes of infertility, with particular reference to advances in the past five years; the second review will look at polycystic ovary syndrome and anovulatory infertility. The role of the general practitioner is to initiate the investigation of both partners and ensure timely onward referral to a specialist clinic. Treatments for infertility are never far from the public eye, often courting controversy and ethical dilemmas. This article aims to provide general practitioners with a balanced and evidence based overview of the latest advances and where they fit into current practice. We referred to the Cochrane database of systematic reviews, NICE guidelines for the investigation and management of infertility (2004), and our knowledge of the current literature. #### Ongoing research questions and projects
Letter: Cerebral oedema in diabetic ketoacidosis.
Authors: B M Frier
Journal: BMJ (1975)

and were accordingly thought to have M.S., four had results between 45-4 and 47-7% and were thought to have other neurological disease (O.N.D.), while the last patient gave a 508°,' result-that is, in the normal range-and her transient disability was thought to be a toxic manifestation of oral contraceptives.Since the relationship of Devic's disease (neuromyeli,tis optica) has long been the subject of debate we studied two clear cases of this condition and both gave results in the O.N.D. range.Your article (like that which appeared in the Lancet3) dwells on the association between measles and M.S. but passes over recent work in relation to other viruses, in particular the finding of high vaccinia anti- body levels in the spinal fluid in M.S.4-6 Nor does it make reference to the extensive re- searches of Daniel,7 who was able to demon- strate a striking association of antibodies against several viruses in M.S. but found no grounds for associating it specifically with measles.A-We are, etc.,
The New Philippine Medical School Established by the Government of the Philippine Islands.
Authors: Paul C. Freer
Journal: JAMA (1907)

Manila, P. I., Sept. 17, 1907. <h3>To the Editor:</h3> —The second annual meeting of the Philippine Islands Medical Association was held in Manila during the early months of 1905, and in the course of the discussions the fact was brought out that the Philippine archipelago has an average of only one physician to every 21,209 of the population, or one to every 430 square miles of territory. The association, consequently, deemed it its duty to bring this matter forcibly to the attention of the government and to request that some action be taken looking toward the establishment of a permanent and modern medical school in the Philippine Islands. The conditions for the success of such a school were very auspicious, as the Bureau of Science and the Bureau of Health would be able to furnish a number of trained men to take part in the teaching. As a result of
Fatal HHV-6 associated encephalitis in an HIV-1 infected patient treated with cidofovir
Authors: Myrto Astriti, Valérie Zeller, David Boutolleau, Agnès Gautheret-Dejean, George Allen, Danielle Seilhean, Henri Agut, François Bricaire, Christine Katlama, Philippe Bossi
Journal: Journal of Infection (2005)
Effect of Prednisolone in Bancroftian Elephantiasis
Authors: P. Jordan
Journal: BMJ (1960)

Molecular orbital calculations and classical potential function calculations were carried out to examine the proposal that the conformations of the hallucinogenic tryptamines and phenylalkylamines are such that their 6-membered aromatic rings and their alkylamino nitrogens are congruent with A ring and N(6) nitrogen atom of lysergic acid diethylamide (the nitrogen of the D ring). The congruent conformation of psilocin is Ψ{C(9)-C(3)-C(β)-C(α)} = 46 ± 10 degrees, φ{C(3)-C(β)-C(α)-N} = 230 ± 20 degrees, θ<sub>1</sub>{C(β)-C(α)-N-C(1N)} = 180 ± 10 degrees, and θ<sub>2</sub>{C(β)-C(α)-N-C(2N)} = 300 ± 10 degrees; that of mescaline is ψ{C(2)-C(1)-C(β)-C(α) = 147 ± 10 degrees and φ{C(l)-C[β]-C(α)-N} = 160 ± 20 degrees. These results show that congruence of psilocin and mescaline with lysergic acid diethylamide is energetically permissible.
Evaluation of Male Sexual Function in Patients with Lower Urinary Tract Symptoms (LUTS) Associated with Benign Prostatic Hyperplasia (BPH) Treated with a Phytotherapeutic Agent (Permixon®), Tamsulosin or Finasteride
Authors: Alexandre R. Zlotta, Pierre Teillac, Jean Pierre Raynaud, Claude C. Schulman
Journal: European Urology (2005)
Natural family planning: Deprives poor people of sex
Authors: M. J Pandit
Journal: BMJ (1993)

often does not have the same motivation, and, particularly in developing countries, a woman may have an unequal say in such a decision.If she feels unhappy living with such uncertainty and decides, from purely unselfish motives, to try a more reliable method of birth control, it is she who has to bear all the guilt imposed on her by the Catholic church.Surely such a situation can have been created only by men, and men with no understand- ing of the problems faced by women.ANNEJEWELL
Multiple atrial macro–re-entry circuits in adults with repaired congenital heart disease: entrainment mapping combined with three-dimensional electroanatomic mapping
Authors: Etienne Delacretaz, Leonard I Ganz, Kyoko Soejima, Peter L Friedman, Edward P Walsh, John K Triedman, Laurence J Sloss, Michael J Landzberg, William G Stevenson
Journal: Journal of the American College of Cardiology (2001)
Allergen‐stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide
Authors: B Nakstad, H Kähler, T Lyberg, B Nakstad
Journal: Allergy (1999)

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen-induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA-DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)-4 and IL-5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA-DR and CD11a/CD18-mediated interactions are also involved in T- and B-cell functions. Birch-pollen (BP) allergens induced CD154 expression on CD3-positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA-DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL-5 and total IgE in BP-supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.
Effectiveness of Influenza Vaccine in Health Care Professionals
Authors: James A. Wilde, Julia A. McMillan, Janet Serwint, Jeanne Butta, Mary Ann O'Riordan, Mark C. Steinhoff
Journal: JAMA (1999)

Data are limited and conflicting regarding the effectiveness of influenza vaccine in health care professionals.To determine the effectiveness of trivalent influenza vaccine in reducing infection, illness, and absence from work in young, healthy health care professionals.Randomized, prospective, double-blind, controlled trial over 3 consecutive years, from 1992-1993 to 1994-1995.Two large teaching hospitals in Baltimore, Md.Two hundred sixty-four hospital-based health care professionals without chronic medical problems were recruited; 49 participated for 2 seasons; 24 participated for 3 seasons. The mean age was 28.4 years, 75% were resident physicians, and 57% were women.Participants were randomly assigned to receive either an influenza vaccine or a control (meningococcal vaccine, pneumococcal vaccine, or placebo). Serum samples for antibody assays were collected at the time of vaccination, 1 month after vaccination, and at the end of the influenza season. Active weekly surveillance for illness was conducted during each influenza epidemic period.Serologically defined influenza infection (4-fold increase in hemagglutination-inhibiting antibodies), days of febrile respiratory illness, and days absent from work.We conducted 359 person-winters of serologic surveillance (99.4% follow-up) and 4746 person-weeks of illness surveillance (100% follow-up). Twenty-four(13.4%) of 179 control subjects and 3 (1.7%) of 180 influenza vaccine recipients had serologic evidence of influenza type A or B infection during the study period. Vaccine efficacy against serologically defined infection was 88% for influenza A (95% confidence interval [CI], 47%-97%; P=.001) and 89% for influenza B (95% CI, 14%-99%; P=.03). Among influenza vaccinees, cumulative days of reported febrile respiratory illness were 28.7 per 100 subjects compared with 40.6 per 100 subjects in controls (P=.57) and days of absence were 9.9 per 100 subjects vs 21.1 per 100 subjects in controls (P=.41).Influenza vaccine is effective in preventing infection by influenza A and B in health care professionals and may reduce reported days of work absence and febrile respiratory illness. These data support a policy of annual influenza vaccination of health care professionals.
Severe Asthma in Adults
Authors: Sally Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Severe asthma remains poorly understood and frustrating to care for, partly because it is a heterogeneous disease. Patients with severe asthma disproportionately consume health care resources related to asthma. Severe asthma may develop over time, or shortly after onset of the disease. The genetic and environmental elements that may be most important in the development of severe disease are poorly understood, but likely include both allergic and nonallergic elements. Physiologically, these patients often have air trapping, airway collapsibility, and a high degree of methacholine hyperresponsiveness. Specific phenotypes of severe asthma are only beginning to be defined. However, describing severe asthma by age at onset (early- vs. late-onset) appears to describe two phenotypes that differ at immunologic, physiologic, epidemiologic, and pathologic levels. In particular, early-onset severe asthma is a more allergic-associated disease than late-onset severe asthma. In addition, patients with severe asthma can be defined on the basis of presence and type of inflammation. Severe asthma with persistent eosinophilia (of either early or late onset) is more symptomatic and has more near-fatal events. However, at least 50% of patients with severe asthma have very little identifiable inflammation. Thus, "steroid resistance" may occur at numerous levels, not all of which are caused by a lack of effect of steroids on inflammation. Treatment remains problematic, with corticosteroids remaining the most effective therapy. However, 5-lipoxygenase inhibitors, anti-IgE, and immunomodulatory drugs are also likely to have a place in treatment. Improving therapy in this disease will require a better understanding of the phenotypes involved.
Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells
Authors: Timea Csak, Michal Ganz, Justin Pespisa, Karen Kodys, Angela Dolganiuc, Gyongyi Szabo
Journal: Hepatology (2011)

The pathogenesis of nonalcoholic steatohepatitis (NASH) and inflammasome activation involves sequential hits. The inflammasome, which cleaves pro-interleukin-1β (pro-IL-1β) into secreted IL-1β, is induced by endogenous and exogenous danger signals. Lipopolysaccharide (LPS), a toll-like receptor 4 ligand, plays a role in NASH and also activates the inflammasome. In this study, we hypothesized that the inflammasome is activated in NASH by multiple hits involving endogenous and exogenous danger signals. Using mouse models of methionine choline-deficient (MCD) diet-induced NASH and high-fat diet-induced NASH, we found up-regulation of the inflammasome [including NACHT, LRR, and PYD domains-containing protein 3 (NALP3; cryopyrin), apoptosis-associated speck-like CARD-domain containing protein, pannexin-1, and pro-caspase-1] at the messenger RNA (mRNA) level increased caspase-1 activity, and mature IL-1β protein levels in mice with steatohepatitis in comparison with control livers. There was no inflammasome activation in mice with only steatosis. The MCD diet sensitized mice to LPS-induced increases in NALP3, pannexin-1, IL-1β mRNA, and mature IL-1β protein levels in the liver. We demonstrate for the first time that inflammasome activation occurs in isolated hepatocytes in steatohepatitis. Our novel data show that the saturated fatty acid (FA) palmitic acid (PA) activates the inflammasome and induces sensitization to LPS-induced IL-1β release in hepatocytes. Furthermore, PA triggers the release of danger signals from hepatocytes in a caspase-dependent manner. These hepatocyte-derived danger signals, in turn, activate inflammasome, IL-1β, and tumor necrosis factor α release in liver mononuclear cells.Our novel findings indicate that saturated FAs represent an endogenous danger in the form of a first hit, up-regulate the inflammasome in NASH, and induce sensitization to a second hit with LPS for IL-β release in hepatocytes. Furthermore, hepatocytes exposed to saturated FAs release danger signals that trigger inflammasome activation in immune cells. Thus, hepatocytes play a key role in orchestrating tissue responses to danger signals in NASH.
Therapeutic Lentivirus-Mediated Neonatal in Vivo Gene Therapy in Hyperbilirubinemic Gunn Rats
Authors: Tuan Huy Nguyen, Marta Bellodi-Privato, Dominique Aubert, Virginie Pichard, Anne Myara, Didier Trono, Nicolas Ferry
Journal: Molecular Therapy (2005)

Crigler–Najjar type 1 disease (CN-1) is a genetic disorder characterized by high levels of unconjugated bilirubin due to the absence of hepatic UDPglucuronosyltransferase (UGT1) activity. Here we show that in vivo neonatal hepatocyte transduction with a lentiviral vector expressing the defective enzyme resulted in long-term correction in Gunn rats, a model of CN-1. Lentiviral vectors harboring the human UGT1 cDNA (approved symbol UGT1A1) under the control of a liver-specific transthyretin promoter were produced. Two-day-old Gunn rats were injected with 50 μl of vector. Bilirubinemia was monitored at 6 weeks and monthly thereafter. At 6 weeks, bilirubinemia was completely normalized in treated animals, whereas it remained around 100 μM in control rats. The level of correction remained stable for up to 42 weeks. Large amounts of bilirubin conjugates were present in the bile of corrected animals. PCR and Western blots confirmed the presence and expression of UGT1 in liver. The estimated proportion of transduced hepatocytes was 40% and transduced cells were not detected in extrahepatic tissues except bone marrow in some animals. This work represents the first demonstration of a complete and permanent correction of hyperbilirubinemia in Gunn rats using lentiviral vectors.
Latest tuberculosis statistics are a "wake-up call for all governments to act immediately"
Authors: P. Moszynski
Journal: BMJ (2010)

In a prospective double-blind study, we compared dexamethasone and placebo in 33 subjects with lumbosacral radicular pain. Of subjects with resting pain, 7/21 improved on dexamethasone, and 4/12 improved on placebo. Of subjects with pain on straight-leg raising, 8/19 improved on dexamethasone and 1/6 on placebo. Of 27 subjects evaluated 1 to 4 years after treatment, 8/16 who had received dexamethasone were asymptomatic or had only occasional mild low-back pain, compared with 7/11 who had received placebo. Thus, dexamethasone is not superior to placebo for either early or long-term relief of lumbosacral radicular pain, but may reduce pain evoked by stretch of acutely inflamed spinal nerve roots.
DRUG TREATMENT FOR INEBRIETY
Authors: O. Lankester
Journal: BMJ (1905)

writing of his own experience during the last twelve months in the drug treatment of inebriates, claims a record of distinct progress, though he declines to announce any "cure," as he considers this term should only be applied to an inebriate who, after treatment, has been an abstainer for at least two years.The following are some practical points to which Dr. Bolton draws
Interference by Spironolactone on Adrenocortical Scintigraphy and Other Pitfalls in the Location of Adrenal Abnormalities in Primary Aldosteronism
Authors: BRAHM SHAPIRO, ROGER GREKIN, MILTON D. GROSS, JOHN E. FREITAS
Journal: Clinical Nuclear Medicine (1994)

A case of primary aldosteronism is presented in which the CT scan was initially misleading, adrenocortical scintigraphy was rendered inaccurate by pharmacological interference of spironolactone, and selective adrenal venous sampling of aldosterone was technically difficult. When dexamethasone suppression adrenocortical scintigraphy was performed with attention to technical detail and exclusion of interference by spironolactone, the causative lesion was scintigraphically demonstrated. This finding was confirmed by the results of venous sampling and the correctly located tumor removed.
The Struggle to Reform Medicare
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1996)

The long debate over the future of Medicare grinds on, but the Republican-controlled Congress and the Clinton administration have agreed on the general thrust of reforms that, if enacted, would reshape this massive health insurance program in fundamental ways. Both sides have acknowledged that the growth of Medicare spending must be slowed appreciably, that beneficiaries should have broader choices about insurance coverage, and that provider-sponsored organizations should be permitted to make contracts directly with the Health Care Financing Administration. The most recent legislative effort parallels the nascent movement by networks of physicians and hospitals to contract directly with private employers . . .
22 year old damaged by aspirin loses compensation claim
Authors: C. Dyer
Journal: BMJ (2002)

The High Court last week cleared the UK government of negligence in not giving a speedier warning 16 years ago about the link between aspirin and Reye's syndrome.

Mr Justice Morland rejected a compensation claim on behalf of Amanda Smith, now aged 22, who had been healthy until as a 6 year old she contracted chickenpox in May 1986 and was given adult aspirin by her mother. Her condition deteriorated into Reye's syndrome, leaving her with brain damage, spastic quadriplegia, epilepsy, and a life …
Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency
Authors: Shin Aizawa, Urara Kohdera, Masaki Hiramoto, Yutaka Kawakami, Ken‐ichi Aisaki, Yohnosuke Kobayashi, Shiro Miwa, Hisaichi Fujii, Hitoshi Kanno
Journal: American Journal of Hematology (2003)

Abstract In this study, possible adverse effects of pyruvate kinase (PK) deficiency on the maturation of erythroid progenitors were investigated. A 4‐year‐old Japanese girl with severe PK deficiency underwent splenectomy to reduce her need for blood transfusions. The spleen was examined a histologically, and the hematopoietic progenitors in the spleen were assayed to evaluate the extramedullary hematopoiesis of this PK‐deficient subject. The number of hematopoietic progenitors including CFU‐GM, BFU‐E and CFU‐GEMM in the spleen of the PK‐deficient patient was much higher than those found in control spleens, indicating enhanced extramedullary hematopoiesis. TUNEL assay demonstrated apoptotic cells in the splenic red pulp of the PK‐deficient patient. The expression of 7A6 antigen was detected in cells isolated from spleen and in cells cultured in vitro, but only in those cells that were positive for glycophorin A. These results provide evidence that the metabolic disturbances in PK deficiency affect not only the survival of red cells but also the maturation of erythroid progenitors, which results in premature cell death, i.e., apoptosis. Am. J. Hematol. 74:68–72, 2003. © 2003 Wiley‐Liss, Inc.
SOME OBSERVATIONS ON THE INFLUENCE OF A MAGNESIUM-DEFICIENT DIET ON RATS, WITH SPECIAL REFERENCE TO RENAL CONCENTRATING ABILITY*
Authors: Andrzej Manitius, Franklin H. Epstein
Journal: Journal of Clinical Investigation (1963)

Impairment of renal concentrating ability is usually considered a hallmark of potassium depletion, occurring early in its development.The presence of this defect is not thought to be re- lated to the cause of potassium depletion (1, 2).Potassium depletion can be induced in rats by a diet deficient in magnesium but containing normal amounts of potassium (3,4).Recently Whang and Welt observed that even an increased supply of potassium in the diet does not prevent mag- nesium-deficient rats from developing depletion of muscle potassium (5).It seemed of interest to study the influence of this peculiar type of potassium depletion on renal concentrating ability.The results indicate that in rats, potassium depletion induced by magnesium deficiency, in contrast to potassium deficiency produced by other means, does not impair the ability of the kidneys to concentrate urine.Strik- ingly different effects upon weight, strength, and behavior were also noted. MATERIAL AND METHODSStudies were carried out on 161 white, male, Sprague-Dawley rats weighing 140 to 200 g at the start of the ex- periment.During the whole experimental period, the rats were fed with one of the four following synthetic diets: normal, magnesium-deficient (referred to in the text as "no-Mg"), potassium deficient ("no-K"), and a diet deficient in both potassium and magnesium ("no-K, no-Mg").The composition of all these diets is given in Table I.Distilled water and food were given ad libitum to all rats except to those of Group II A (see below), pair-fed controls whose food, but not water, was restricted.