tbuckley/cabot-search huggingface dataset:
Incidence of non-melanocytic skin cancer treated in Australia
Authors: G. G Giles, R. Marks, P. Foley
Journal: BMJ (1988)

In 1985, as part of a national random household omnibus survey by a market research company, 30 976 Australians (mostly of European origin) were asked whether they had ever been treated by a doctor for skin cancer. The treating doctor or hospital was then approached for confirmation of the diagnosis of all those people who claimed to have been so treated within the past 12 months. Demographic data were also collected, permitting analysis by age, sex, country of birth, current residence, and skin reaction to strong sunlight. Melanomas accounted for less than 5% of the tumours treated. The world standardised incidence of melanoma was 19/100 000 population. The standardised incidence of treated non-melanocytic skin cancer in Australia was estimated to be 823/100 000. The standardised rates for basal cell carcinoma and squamous cell carcinoma were 657 and 166/100 000 respectively, yielding a standardised rate ratio of about 4:1. Standardised rates based on medically confirmed cases only were 555, 443, and 112/100 000 for all non-melanocytic skin cancers, basal cell carcinomas, and squamous cell carcinomas respectively. Significant differences and trends in incidence were noted with respect to age and sex. Rates in men were higher than those in women but significantly so only after the age of 60. People born in Australia had a rate of 936/100 000 compared with 402/100 000 in British migrants. Rates for non-melanocytic skin cancer showed a gradient with respect to latitude within Australia. The rate in people residing north of 29°S was 1242/100 000 compared with a rate of 489/100 000 in those living south of 37°S. A person9s skin reaction to strong sunlight was a good indicator of the risk of skin cancer, tanning ability being inversely related to its incidence. The rate in those who always burnt and never tanned when exposed to strong sunlight was 1764/100 000 compared with a rate of 616/100 000 in those who always tanned and never burnt. These findings have important implications for public education programmes in relation to exposure to sunlight in Australia.
A comparison of the efficacy of naproxen sodium and a paracetamol/dextropropoxyphene combination in the treatment of soft-tissue disorders.
Authors: C. J. Abbott, T. A. Bouchier-Hayes, H. A. Hunt
Journal: British Journal of Sports Medicine (1980)

Ninety-eight patients were admitted to a single-blind parallel study comparing the efficacy of naproxen sodium with a paracetamol/dextropropoxyphene combination in the treatment of soft-tissue disorders. The two study groups were well matched in all respects. After seven days of treatment patients in the naproxen sodium group had less residual symptoms and more of them were considered cured. These patients also had a significantly lower mean-pain-score, tended to have less daily symptoms and recorded a significantly greater initial improvement in their condition. Fewer side-effects were recorded by the naproxen sodium-treated patients. One patient from each group withdrew from the study because of side-effects. It was concluded that in the treatment of non-articular soft-tissue disorders the use of a rapidly-acting withdrew anti-inflammatory drug, naproxen sodium, gave a better clinical response than did treatment with a simple analgesic combination.
An Address on Syphilis as an Imitator
Authors: J. Hutchinson
Journal: BMJ (1879)

MR. PRESIDENT AND GENTLEMEN,-An idea has much occupied my mind, during the last few years, which seems to considerably simplify ,our creed as regards the nature of the very various forms of disease which are caused by syphilis.It is, that we ought to recognise in syphilitic forms of inflammation imitations, with certain differences, of the other -and more common types of diseased action which occur without any connection with specific taint.The fact, as a matter of clinical observa- tion, must have been obvious to all for long; and the names which the various types of syphilitic eruption have received recognise it.As a rule, we are content to apply the adjective " syphilitic" to some substan- tive which designates a well-known form of non-specific skin-disease, "syphilitic psoriasis", "'syphilitic roseola", and the like.This recognition of the doctrine which I purpose to propound to-day, in some detail, is so general and so old, that I might, perhaps, almost need to apologise for making it the subject of a special discourse, were it not that I hope to be able to show that it has ramifications which have as yet scarcely received the attention they deserve.To my own mind, I may acknowledge that this general law of imitation or simulation has been of the greatest possible service; and that it has helped me to a clear view of much that was previously obscure.There is no difficulty in explaining why syphilis in its action upon the solids and fluids of the human body should be an imitator of old types, and not an originator of new ones, if we admit, as probable, that almost all possible forms of morbid process existed already independently of it.The introduction of the syphilitic virus into the system simply gives a tendency to derangement of cell-nutrition, resulting in local inflammation.All such derangements must be regulated in their development by anatomical con- ditions and physiological laws.Certain structures exist which will be attacked, and their number and variety is not unlimited.There are in the skin, for example, certain glands, papille vascular areas, and special appendages; and any of these may be attacked by disease; and the possible variety as to its anatomical location, although great, is still xestricted.Syphilis cannot devise for itself any new set of organs, nor can it lay down any new lines along which morbid action, once originated, may spread.It must work in the old grooves, and travel by the
Design of Phase I Combination Trials: Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee
Authors: Channing J. Paller, Penelope A. Bradbury, S. Percy Ivy, Lesley Seymour, Patricia M. LoRusso, Laurence Baker, Larry Rubinstein, Erich Huang, Deborah Collyar, Susan Groshen, Steven Reeves, Lee M. Ellis, Daniel J. Sargent, Gary L. Rosner, Michael L. LeBlanc, Mark J. Ratain
Journal: Clinical Cancer Research (2014)

Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistic and regulatory challenges. The phase I trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute Investigational Drug Steering Committee developed a set of recommendations for the phase I development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biologic or pharmacologic rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase I clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamics (i.e., biomarker).
Marijuana use in early pregnancy increases child's risk of cancer
Authors: Roger Dobson
Journal: BMJ (2006)

Mothers who use marijuana in the first trimester may increase the risk of their child developing neuroblastoma, the second most common solid tumour found in children, a US study has found.

The results of the case control study to investigate the role of illicit drugs in the development of the tumour show that mothers' use of any illicit or recreational drug during pregnancy was associated with an increased risk of neuroblastoma in the offspring (odds ratio 1.82 (95% confidence interval 1.1 to 3.0) ( Cancer Causes and Control 2006;7:663-9). …
Medical Ethics and Torture
Authors: Albert R. Jonsen
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Torture, especially with the cooperation of persons dedicated to healing, is a moral evil. When political involvement in medical care and access to it leads to the physical and mental destruction of human beings, it degrades the entire medical profession. Yet despite the profession's concern that its members should "be of help, but above all, do no harm," the medical community often remains ignorant of instances where politicized physicians and other medical personnel have become agents of a tyrannical state. The dilemmas that physicians may experience in carrying out a political directive that violates the fundamental ethics of their profession are now clearly in focus. Should physicians force-feed political prisoners who are fasting in protest? Should physicians revive prisoners so that they can be returned to torture? Should physicians certify prisoners as being physically "fit" for torture? Should psychiatric hospitals agree to the imprisonment of political dissidents?
Monophasic Action Potentials in Man
Authors: RALPH SHABETAI, BORYS SURAWICZ, WILLIAM HAMMILL
Journal: Circulation (1968)

Monophasic action potentials with an amplitude of up to 70 mv were recorded with suction electrodes from the endocardial surface of the right atrium and both ventricles during diagnostic cardiac catheterization. The method was simple and safe. The monophasic action potential of human beings had the same shape and the same relation to the electrocardiogram as the transmembrane action potential of animals has. Also changes in heart rate and administration of calcium and digitalis had the same effect on the monophasic action potential of man as on the transmembrane action potential of animals. When injections of contrast material into the coronary arteries produced T-wave changes, the monophasic action potential from the ventricle perfused by the contrast medium lengthened, but the monophasic action potential from the other ventricle did not change. Our study suggests that the monophasic action potential may be helpful in estimating the refractory period at the site of recording and in explaining the pathogenesis of abnormal repolarization in the electrocardiogram.
Galectin-1 exerts immunomodulatory and protective effects on concanavalin a-induced hepatitis in mice
Authors: Luca Santucci, Stefano Fiorucci, Francesco Cammilleri, Giuseppe Servillo, Barbara Federici, Antonio Morelli
Journal: Hepatology (2000)

Galectin-1, an endogenous lectin with immunomodulatory activities, induces selective, Fas-independent apoptosis of activated T cells. The aim of the present study was to evaluate the effect galectin-1 exerts on concanavalin A (Con A)-induced hepatitis, a T-cell-dependent model of liver injury. Con A administration resulted in liver injury, as shown by the increased transaminase plasma levels and liver DNA fragmentation, and caused spleen T-cell activation, which was associated with a strong increment in liver infiltrating T helper cells. Moreover, Con A injection leads to a marked increase in plasma tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) levels. Galectin-1 pretreatment dose-dependently prevented both liver injury and T-helper cell liver infiltration induced by Con A. In vivo and in vitro experiments indicated that the protective effects of galectin-1 depend on the selective elimination of Con A-activated T cells. In addition, galectin-1 almost completely prevented the Con A-induced increase in plasma TNF-alpha and IFN-gamma, an effect that was, at least in part, independent on the elimination of activated T helper cells, because galectin-1 prevented lipopolysaccharide (LPS)-induced release of TNF-alpha and IFN-gamma also from macrophages in vitro, without affecting their viability. The present study suggests that galectin-1 is potentially useful in the treatment of T-cell-mediated human liver disorders.
The Mechanism of Thyroid Hormone Secretion
Authors: WILLIAM P. DEISS
Journal: Annals of Internal Medicine (1968)

Release of thyroid hormones from peptide linkage in follicular colloid to the circulation is normally carefully modulated by pituitary thyrotrophin. Secretion of these hormones is now thought to occur by a sequence of intricate, coordinated changes within the stimulated cell. This sequence begins with the formation of colloid droplets derived from portions of the follicular colloid brought into the cell by pinocytosis. Lysosomes that contain hydrolytic enzymes move from the base of the cell toward the apex to fuse with these droplets. Within these new organelles, phagolysosomes, lysis of thyroglobulin occurs to release the hormonal amino acids thyroxine and triiodothyronine. Evidence for this sequence coming from both morphological and biochemical experiments has been reviewed. The possibility that derangement of this sequence plays a role in human thyroid disease has been suggested.
Plasma Concentration of C-Reactive Protein and Risk of Developing Peripheral Vascular Disease
Authors: Paul M. Ridker, Mary Cushman, Meir J. Stampfer, Russell P. Tracy, Charles H. Hennekens
Journal: Circulation (1998)

Background —Among apparently healthy men, elevated levels of C-reactive protein (CRP), a marker for systemic inflammation, predict risk of myocardial infarction and thromboembolic stroke. Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease (PAD) is unknown. Methods and Results —Using a prospective, nested, case-control design, we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians’ Health Study who subsequently developed symptomatic PAD (intermittent claudication or need for revascularization) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months. Median CRP levels at baseline were significantly higher among those who subsequently developed PAD (1.34 versus 0.99 mg/L; P =.04). Furthermore, the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest (referent) to highest quartile of CRP were 1.0, 1.3, 2.0, and 2.1 ( P trend =.02). Compared with those with no clinical evidence of disease, the subgroup of case patients who required revascularization had the highest baseline CRP levels (median=1.75 mg/L; P =.04); relative risks from lowest to highest quartile of CRP for this end point were 1.0, 1.8, 3.8, and 4.1 ( P trend =.02). Risk estimates were similar after additional control for body mass index, hypercholesterolemia, hypertension, diabetes, and a family history of premature atherosclerosis. Conclusions —These prospective data indicate that among apparently healthy men, baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis.
Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer
Authors: Tsun Leung Chan, Siu Tsan Yuen, Chi Kwan Kong, Yee Wai Chan, Annie SY Chan, Wai Fu Ng, Wai Yin Tsui, Michelle WS Lo, Wing Yip Tam, Vivian SW Li, Suet Yi Leung
Journal: Nature Genetics (2006)
1328 IL28B GENOTYPE HAS VARIABLE INFLUENCE ON EARLY VIRAL KINETICS, BUT NO INFLUENCE ON SUSTAINED VIROLOGICAL RESPONSE DURING TREATMENT FOR RECENT HEPATITIS C VIRUS INFECTION
Authors: J. Grebely, G.V. Matthews, M. Hellard, V. Suppiah, K. Petoumenos, T. Applegate, B. Yeung, W. Rawlinson, J. Feld, A.R. Lloyd, D. Booth, J.M. Kaldor, J. George, G.J. Dore
Journal: Journal of Hepatology (2011)
Allergic Sino-orbital Mycosis
Authors: Walter Brummund
Journal: JAMA (1986)

We present a case of pansinusitis with orbital involvement associated with an allergic response to the fungus Curvularia (Cochliobolus) lunata. Key elements to the diagnosis included a predominant eosinophilic response of the sinus mucosa, the presence of a characteristic mucoid exudate containing fungal hyphae, peripheral blood eosinophilia, serum precipitins against C lunata, elevated serum total and Curvularia-specific IgE and IgG concentrations, and immediate cutaneous reactivity to C lunata antigen. This report suggests that an exaggerated allergic response should be considered in the pathogenesis of pansinusitis. The presence of fungal hyphae in sinus mucosal specimens should alert the physician to the possibility of this disease. Sinus fungal cultures, as well as thorough immunologic evaluation, of such patients is recommended.
Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH
Authors: Kejian Zhang, Michael B. Jordan, Rebecca A. Marsh, Judith A. Johnson, Diane Kissell, Jarek Meller, Joyce Villanueva, Kimberly A. Risma, Qian Wei, Peter S. Klein, Alexandra H. Filipovich
Journal: Blood (2011)
Increased susceptibility of differentiated mononuclear phagocytes to productive infection with human immunodeficiency virus-1 (HIV-1).
Authors: E A Rich, I S Chen, J A Zack, M L Leonard, W A O'Brien
Journal: Journal of Clinical Investigation (1992)

Differences in susceptibility to infection of most mononuclear phagocytes with HIV-1 are not known. We investigated the relative susceptibility of autologous freshly isolated blood monocytes (MN), MN cultured in vitro to allow differentiation (CM), and alveolar macrophages (AM) from healthy subjects to productive infection with HIV-1. Cells were infected with the macrophage tropic strain HIV-1JR-FL and p24 gag antigen levels measured in supernatants by ELISA. Freshly isolated MN had negligible levels of p24 in supernatants. In contrast AM had peak p24 levels of 4145 +/- 1456 pg/ml, mean +/- SE, and CM 9216 +/- 3118. As a measure of entry and extent of reverse transcription, levels of viral DNA in infected mononuclear phagocytes were analyzed by quantitative polymerase chain reaction (PCR). The data using primers that amplify all transcripts including incompletely formed reverse transcripts indicated that differences in entry of the virus may contribute to differences in virus production observed with MN, AM, and CM. Other primer pairs that detect intermediate and full-length double-stranded DNA showed that the ability to complete reverse transcription was similar among these mononuclear phagocytes. Since the lung is a major site of opportunistic infection and noninfectious complications in HIV-1-infected individuals, this increase in productive infection with HIV-1 in AM compared with MN could contribute to the immunopathogenesis of the lung disorders seen in the acquired immunodeficiency syndrome.
Lind and scurvy: 1747 to 1795
Authors: U Trohler
Journal: Journal of the Royal Society of Medicine (2005)

Lind’s Treatise of the Scurvy1 is a good illustration of the basis for mid-18th century judgement and decision-making in at least two respects: it quotes the contributions of others at length, and its therapeutic recommendations had little impact.2,3 Lind dedicated his book to Lord Anson because an account of Anson’s circumnavigation published in 1748 had prompted Lind’s interest in scurvy: at least 380 out of a crew of 510 on one of Anson’s ships had died of the disease. When Lind began to read the literature on scurvy, he realized that the only existing descriptions of the disease were by lay seamen and doctors who had never been to sea. ‘No physician conversant with this disease at sea had undertaken to throw light upon the subject,’ and Lind felt that this was one of the reasons why there was so much confusion about the diagnosis, prevention and cure of the disease. As Lind wrote bluntly: ‘Indeed, before the subject could be set in clear and proper light, it was necessary to remove a great deal of rubbish’1 (p. viii).
Wegener's granulomatosis in two sisters.
Authors: M A Muniain, J C Moreno, R Gonzalez Campora
Journal: Annals of the Rheumatic Diseases (1986)

We describe two sisters with necrotising granulomas. The intervals between the onset of symptoms and diagnosis were eight and nine years. The pathological findings showed necrotising granulomas in both patients, this being consistent with a diagnosis of pathergic (Wegener9s) granulomatosis. The one patient that accepted treatment responded well to cyclophosphamide, though the facial lesions responded only to radiation therapy. Since the second was almost asymptomatic we conclude that relatives of patients with Wegener9s disease should be investigated.
Pathogenesis of pulmonary aspergillosis. Granulocytopenia versus cyclosporine and methylprednisolone-induced immunosuppression.
Authors: J Berenguer, M C Allende, J W Lee, K Garrett, C Lyman, N M Ali, J Bacher, P A Pizzo, T J Walsh
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Patients with chemotherapy-induced granulocytopenia for neoplastic diseases and those receiving cyclosporin A plus corticosteroids for prevention and treatment of organ transplant rejection are two immunologically distinct patient populations with high risks for development of invasive pulmonary aspergillosis. In order to compare the pathogenesis of aspergillosis in these two high-risk populations and to further characterize the role of cyclosporin A in development of pulmonary aspergillosis, we studied the patterns of infection and inflammation in two clinically applicable rabbit models of invasive pulmonary aspergillosis. There were striking differences in the patterns of infection and inflammation of invasive pulmonary aspergillosis according to the type of underlying immune defect. Among rabbits challenged with the same intratracheal inoculum, there was a 100% mortality for invasive pulmonary aspergillosis in profoundly granulocytopenic rabbits in comparison with a 100% mortality for invasive pulmonary aspergillosis in profoundly granulocytopenic rabbits in comparison with a 100% survival in rabbits immunosuppressed with cyclosporin A plus methylprednisolone (CsA+MP). Lesions of pulmonary aspergillosis in granulocytopenic rabbits consisted predominantly of coagulative necrosis, intraalveolar hemorrhage, and scant mononuclear inflammatory infiltrate. By comparison, pulmonary foci in rabbits immunosuppressed by CsA+MP consisted mainly of neutrophilic and monocytic infiltrates, inflammatory necrosis, and scant intraalveolar hemorrhage. There was extensive infiltration by hyphae with angioinvasion in granulocytopenic rabbits, whereas conidia in various stages of germination predominated in CsA+MP treated animals in which there was a paucity of hyphae or angioinvasion. Extrapulmonary disease predominated in granulocytopenic rabbits. Methylprednisolone was the major immunosuppressive drug in rabbits treated with CsA+MP. Cyclosporin A alone did not increase the progression of pulmonary aspergillosis and did so only when used chronically with methylprednisolone.
Tumor necrosis factor α (TNF-α) receptor-II is required for TNF-α–induced leukocyte-endothelial interaction in vivo
Authors: Unni M. Chandrasekharan, Maria Siemionow, Murat Unsal, Lin Yang, Earl Poptic, Justin Bohn, Kagan Ozer, Zhongmin Zhou, Philip H. Howe, Marc Penn, Paul E. DiCorleto
Journal: Blood (2006)