tbuckley/cabot-search huggingface dataset:
The Medicinal Leech
Authors: Stephen L. Adams
Journal: Annals of Internal Medicine (1988)

Leeches have been used in health care since ancient times by physician and layman alike. As just one of several methods of bloodletting, the leech became the focus of a science that included such subjects as indications, modes of attachment, complications, and relative contraindications. The popularity of leeching has varied immensely over the years. In the 19th century, this annelid saw its numbers decimated because of protean medicinal indications. The leech lost its hold on the practice of medicine in the early 20th century. Recently, the use of leeches has resurged in both the lay and the scientific communities.
Industry-Sponsored Research: Author's Reply
Authors: Julio Sotelo
Journal: PLoS Medicine (2006)

Joal HillI read with interest the debate about for-profi t versus non-profi t institutional review boards (IRBs) [1], but was disappointed that no one addressed the ability (or inability) of for-profi t IRBs to review studies with the local context of research subjects in mind and then monitor what actually occurs during the consent process throughout the research trial.To my mind the "bigness" of for-profi t IRBs may be more of an impediment in protecting research subjects than their inherent confl ict of interest.Our IRB has reviewed consent forms approved by central/for-profi t IRBs that contained obvious errors such as schemas that did not match protocol narrative and use of eight point font in a study of geriatric subjects.Even when the initial review is outstanding, it seems a practical impossibility for a single IRB to provide meaningful monitoring of the actual consent process and implementation of the protocol at sites throughout the country.The greater "effi ciency" of for-profi t IRBs is only a meaningful benefi t if increased speed can be shown not to occur at the expense of careful review of consent forms, real understanding of the local research context, and a commitment to audit the informed consent process throughout the study for the protection of research subjects, including ongoing education and advice for researchers and their teams.This is not to say that all local IRBs perform this function as they should, but it does seem almost impossible for one IRB to perform local review and oversight for research sites around the nation in a way that really makes a difference for the men, women, and children who give of their time and their bodies so that society can benefi t.
STUDIES ON THE MECHANISM OF FEVER ACCOMPANYING DELAYED HYPERSENSITIVITY
Authors: Elisha Atkins, Joseph D. Feldman, Lorraine Francis, Ellen Hursh
Journal: The Journal of Experimental Medicine (1972)

Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization. The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.
THE TREATMENT OF TYPHOID AND DYSENTERY CARRIERS WITH SUCCINYLSULFATHIAZOLE
Authors: WILLIAM M. M. KIRBY
Journal: JAMA (1942)

The discovery that certain derivatives of sulfanilamide are relatively poorly absorbed from the gastrointestinal tract marked the beginning of a new era in intestinal antisepsis. One of these compounds, sulfaguanidine, has been given extensive clinical trial and has been found to be of value in the treatment of patients with acute bacillary dysentery<sup>1</sup>and of dysentery carriers.<sup>2</sup>In cases of typhoid,<sup>3</sup>the typhoid carrier state<sup>4</sup>and ulcerative colitis,<sup>3</sup>the results have been discouraging. Patients undergoing extensive operations on the bowel were also given this drug with the hope that reduction of the number of gram-negative bacilli in the intestinal contents might cause a decrease in the incidence of infections of the peritoneal cavity due to fecal contamination. It was not entirely satisfactory for this purpose, partly because it was absorbed into the blood stream to such an extent that it gave rise to frequent and
The mark 2 human genome: a word of advice from us down here
Authors: J D Gillies, P N Le Souef
Journal: BMJ (1995)

The present human form is the first draft of a cosmic design. Our concern is that the Designer has derived such amusement from us that He may not proceed further towards perfection.

First models always are defective and improvement is expected in mark 2 versions. The present human is riddled with design errors resulting perhaps from undue haste to get the monkey out of us. This is nothing compared with the camel, of course, which is clearly a prototype raced into production. The following is respectfully submitted for consideration by the Almighty in the mark 2 human genome.

First children have a higher morbidity than subsequent infants. The second child has the lowest risk and should be born first. This would ensure that parents have more experience since this is their second child, and the risk of frustration-induced child abuse would fall. Possibly children should be born to their grandparents, who have time, experience, patience, and often the wealth required.

Hair was necessary for protection of the cave man, but now it has been relegated to an art form—serving no function. The more genetically advanced amongst us already lose our hair. Infants are born bald but our Creator has allowed later development of this useless material. We should be bald throughout life.

Humans have a big brain, which has made our head too large, and we look silly beside an emu. Imagine an architect or engineer designing a heavy controlling unit linked to the main functioning area by a flexible, exposed, and poorly supported device like our neck. Nobody would accept it. Our suggestion encompasses the following principles. The controlling unit (head and brain) should be located within the chest providing added protection and a central location which would reduce nerve connection failures. The eyes should be like those of …
Dr. McCormack's Successful Work.
Authors: G. C. Savage.
Journal: JAMA (1906)

Nashville, Tenn., Feb. 5, 1906. <h3>To the Editor:</h3> —I had already learned much of what Dr. J. N. McCormack, as medical organizer of the American Medical Association, has been doing in other states, but was not fully impressed with the importance of his work until I heard him at Gallatin one week ago. This was his first lecture in middle Tennessee, and I was so anxious to learn something of the nature of his work that I visited Gallatin for the purpose of hearing him. He spoke in the courthouse at 2 p. m. to an audience composed of medical men, ministers, lawyers, county officials, business men, teachers and women. Every one present listened intently throughout his talk, which was entertaining, interesting and instructive. I am sure that the members of the county society were made more determined to perform their duties to each other and to the public better
THE INVESTIGATION OF POLYMORPHIC LTGHT ERUPTION IN IDENTICAL TWINS
Authors: W. FRAIN-BELL, BERNARD MASON
Journal: British Journal of Dermatology (1968)

Journal Article THE INVESTIGATION OF POLYMORPHIC LTGHT ERUPTION IN IDENTICAL TWINS Get access W. FRAIN‐BELL, W. FRAIN‐BELL Department of Dermatology, Royal Infirmary, Dundee Search for other works by this author on: Oxford Academic Google Scholar BERNARD MASON BERNARD MASON Department of Dermatology, Royal Infirmary, Dundee Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 5, 1 May 1968, Pages 314–322, https://doi.org/10.1111/j.1365-2133.1968.tb12305.x Published: 01 May 1968 Article history Accepted: 22 December 1967 Published: 01 May 1968
Luxembourg is to allow euthanasia from 1 April
Authors: R. Watson
Journal: BMJ (2009)

Luxembourg has become the third European country, after the Netherlands and Belgium, to legalise euthanasia in certain cases. The new legislation, which is accompanied by a parallel text on palliative care, will enter into force on 1 April.

The law stipulates that doctors who carry out euthanasia and assisted suicides will not face “penal sanctions” or civil lawsuits as long as they first consult a colleague to ensure that the patient has a terminal illness, is in a “grave and incurable condition,” and has repeatedly asked for the right to die.

Within eight days of helping a patient to …
Abstract 3039: Protein kinase C-δ mediated KIT recycling in colon cancers.
Authors: Mi Sun Park, Won Kyu Kim, Meiying Song, Hoguen Kim
Journal: Cancer Research (2013)

Abstract Abnormal signals through the receptor tyrosine kinase (RTK) moieties are important in colon cancer both for tumorigenesis and drug targets. Wild type KIT, one of the RTKs, had been reported to be highly expressed in some colon cancers, however little is known about the functional aspects and roles of stem cell factor (SCF) dependent activation in colon cancers. We characterized colorectal cancers with KIT expression and analyzed the biological alterations of KIT after stimulation of SCF and its impact on the downstream signals. We identified wild type KIT is expressed in some colon cancer cell lines, activated by SCF, and subsequently activated AKT and ERK signaling pathways. We also demonstrated that KIT expression was gradually decreased after SCF stimulation due to lysosomal degradation of activated KIT. We found PKC activation rescues KIT by inhibiting ubiquitination of KIT after SCF treatment. Among the various types of PKCs, PKC-δ directly bound to wild type KIT and rescued SCF-KIT complexs. Additionally, we demonstrated that KIT and PKC-δ are concomitantly activated in the colon cancer tissues with wild type KIT expression, and the expression of KIT is correlated with poor survival. Based on these findings we concluded that downstream signal activation after SCF-KIT binding is continuously accomplished by the PKC-δ activation and subsequent KIT recycling. These signal pathways induced by SCF and PKC-δ mediated KIT recycling play important roles in colon cancer progression. Citation Format: Mi Sun Park, Won Kyu Kim, Meiying Song, Hoguen Kim. Protein kinase C-δ mediated KIT recycling in colon cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3039. doi:10.1158/1538-7445.AM2013-3039
Chloramphenicol-Induced Hemolysis in Caucasian Glucose-6-Phosphate Dehydrogenase Deficiency
Authors: Ronald P. McCaffrey, Charles H. Halsted, Mohammed Fathy Abdel Wahab, R. P. Robertson
Journal: Annals of Internal Medicine (1971)

Three white G6PD-deficient patients suffered severe hemolytic reactions during treatment for typhoid fever with chloramphenicol. Two of these patients were studied when free of infection to determine the hemolytic potential of chloramphenicol in the noninfected G6PD-deficient white person. It was found to be mildly hemolytic under these conditions, suggesting that a drug-disease synergism was primarily responsible for the clinical hemolytic reactions. The febrile state itself, or changes in plasma amino acids accompanying infection, may be responsible for disease-related hemolysis.
Abstract P1-08-03: Alternative Dosing Regimens with Tarceva in a Mammary Cancer Model: Effects on Efficacy and Potential Effects on Toxicity
Authors: RA Lubet, K Iwata, E Szabo, CJ. Grubbs
Journal: Cancer Research (2010)

Abstract The EGFR inhibitors (e.g., Tarceva) have been effective in preventing cancer in multiple animal models, including ER positive breast, head and neck, and urinary bladder cancers. Although Tarceva is less toxic than most classical cytotoxic therapies, the development of a skin rash in greater than 35% of patients is a significant impediment to its use in a preventive setting. We, therefore, tested whether alternative dosing regimens would still achieve preventive efficacy. Female Sprague-Dawley rats were administered a single IV dose of methylnitrosourea at 50 days of age. Beginning 5 days later, rats were administered Tarceva (6 mg/kg BW) by gavage. In the first study, three different protocols were employed: (1) dosing with Tarceva daily (7X/week), (2) dosing with Tarceva for one day followed by one day of vehicle treatment, and (3) two days of dosing with Tarceva followed by two days of dosing with vehicle treatment. These treatment regimens resulted in 94, 58, and 77% decreases, respectively, in cancer multiplicity when compared to rats receiving vehicle alone. In a second ongoing study, we are evaluating the following alternative dosing schedules. MNU treated rats are receiving either: (1) daily dosing with 6 mg/kg BW (total of 42 mg/week); (2) dosing 6 mg/kg BW, 2 days on-2 days off (total of 21 mg/week): (3) weekly dosing with a single dose of 42 mg; and (4) daily dosing with the vehicle. The various Tarceva treatment regimens have currently reduced palpable mammary tumor multiplicity by 82, 66, and 71%, respectively. These data imply that by significantly altering the dosing of Tarceva, including a dose of once per week, most of the preventive efficacy is retained. Pharmacokinetic studies from these protocols showed a t½ of &amp;lt;8 hours; implying that sub-effective serum levels were achieved within 48 hours of the last dose. Whether these altered protocols may affect the induced skin rash in women is a significant and practical question. Supported by NCI contract number HHSN261200433001C. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-08-03.
Learning to live in a medical household
Authors: K. Billings
Journal: BMJ (2004)

My two younger brothers and I have had a very medicine oriented upbringing. Our father is a surgeon with a special interest, and our mother is a general practitioner. Having reached the age of 21, I thought it would be interesting to reflect on how our childhoods have been affected by our parents' profession. My brothers and I have grown up with very different career aspirations to theirs.

I first began to get an idea of what my parents' jobs involved when I was 5 years old. A local parent asked me what my mother's profession was, and I replied, very proud of my knowledge, that she was a general practitioner. Further questioning as to what this actually entailed revealed my belief that it meant she worked two days a week. I was taught some more about my mother's work that evening.

While I was always happy to discuss my mother's profession, I used …
Fusion of the nucleoporin gene NUP98 to HOXA9 by the chromosome translocation t(7;11)(p15;p15) in human myeloid leukaemia
Authors: Takuro Nakamura, David A. Largaespada, Maxwell P. Lee, Laura A. Johnson, Kazuma Ohyashiki, Keisuke Toyama, Sai Juan Chen, Cheryl L. Willman, I-Ming Chen, Andrew P Feinberg, Nancy A. Jenkins, Neal G. Copeland, John D. Shaughnessy
Journal: Nature Genetics (1996)
Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study
Authors: L A Mandl, K H Costenbader, J F Simard, E W Karlson
Journal: Annals of the Rheumatic Diseases (2008)

The "fetal origins of adult disease" hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual's future risk of rheumatoid arthritis (RA).The relationship between birthweight and the risk of incident RA was studied in 87 077 women followed prospectively in the Nurses' Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breastfeeding, and body mass index (BMI) at age 18.In an age-adjusted model, birthweight >4.54 kg vs birthweight 3.2-3.85 kg was associated with a two-fold increased risk of RA (relative risk (RR) = 2.1, 95% CI 1.4 to 3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR = 2.0, 95% CI 1.3 to 3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA (RR = 2.1, 95% CI = 1.2 to 3.6).In this large prospective cohort, birthweight >4.54 kg was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.
Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1
Authors: Kate L Jeffrey, Tilman Brummer, Michael S Rolph, Sue M Liu, Nuria A Callejas, Raelene J Grumont, Corine Gillieron, Fabienne Mackay, Shane Grey, Montserrat Camps, Christian Rommel, Steve D Gerondakis, Charles R Mackay
Journal: Nature Immunology (2006)
Fewer new drugs from the pharmaceutical industry
Authors: D. Taylor
Journal: BMJ (2003)

In 2002 spending on medicines exceeded $400bn (£248bn; €377bn) worldwide. Optimists in the pharmaceutical industry believe that the global market for their products will go on expanding by around 10% a year, with the United States continuing to lead towards higher per capita outlays.1 Expenditure on research by the pharmaceutical industry is also increasing worldwide. It is now over $45bn a year—twice the sum recorded at the start of the 1990s—and projected to rise to $55bn by 2005-6.2 Concerns are growing, however, about the productivity of research being funded by the major pharmaceutical companies.

Industry leaders have argued that advances in areas such as genomics will in time identify many new targets for pharmaceuticals to act on.3 Yet some analysts fear that current programmes will not deliver innovations that are capable of generating the earnings currently coming from high selling medicines close to the end of the lives of their patents. The changed nature of future pharmaceutical products and the marketing support they need may mean that the business model underpinning the mainstream pharmaceutical industry …
In vitro chemical and cellular tests applied to uranium trioxide with different hydration states.
Authors: E Ansoborlo, J Chalabreysse, M H Hengé-Napoli, E Pujol
Journal: Environmental Health Perspectives (1992)

A simple and rapid in vitro chemical solubility test applicable to industrial uranium trioxide (UO3) was developed together with two in vitro cellular tests using rat alveolar macrophages maintained either in gas phase or in alginate beads at 37 degrees C. Industrial UO3 was characterized by particle size, X-ray, and IR spectra, and chemical transformation (e.g., aging and hydration of the dust) was also studied. Solvents used for the in vitro chemical solubility study included carbonates, citrates, phosphates, water, Eagle's basal medium, and Gamble's solution (simulated lung fluid), alone, with oxygen, or with superoxide ions. Results, expressed in terms of the half-time of dissolution, according to International Commission on Radiological Protection (ICRP) classification (D,W,Y), varied for different hydration states of UO3, showing a lower solubility of hydrated UO3 in solvents compared to basic UO3 or UO3 heated at 450 degrees C. Two in vitro cellular tests on cultured rat alveolar macrophages (cells maintained in gas phase and cells immobilized in alginate beads) were used on the same UO3 samples and generally showed a lower solution transfer rate in the presence of macrophages than in the culture medium alone. The results of in vitro chemical and cellular tests were compared, with four main conclusions: a good reproducibility of the three tests in Eagle's basal medium the effect of hydration state on solubility, the classification of UO3 in terms of ICRP solubility criteria, and the ability of macrophages to decrease uranium solubility in medium.
Combustion products of 1,3-butadiene are cytotoxic and genotoxic to human bronchial epithelial cells.
Authors: W J Catallo, C H Kennedy, W Henk, S A Barker, S C Grace, A Penn
Journal: Environmental Health Perspectives (2001)

Adverse health effects of airborne toxicants, especially small respirable particles and their associated adsorbed chemicals, are of growing concern to health professionals, governmental agencies, and the general public. Areas rich in petrochemical processing facilities (e.g., eastern Texas and southern California) chronically have poor air quality. Atmospheric releases of products of incomplete combustion (e.g., soot) from these facilities are not subject to rigorous regulatory enforcement. Although soot can include respirable particles and carcinogens, the toxicologic and epidemiologic consequences of exposure to environmentally relevant complex soots have not been well investigated. Here we continue our physico-chemical analysis of butadiene soot and report effects of exposure to this soot on putative targets, normal human bronchial epithelial (NHBE) cells. We examined organic extracts of butadiene soot by gas chromatography-mass spectrometry (GC-MS), probe distillation MS, and liquid chromatography (LC)-MS-MS. Hundreds of aromatic hydrocarbons and polycyclic aromatic hydrocarbons with molecular mass as high as 1,000 atomic mass units were detected, including known and suspected human carcinogens (e.g., benzo(a)pyrene). Butadiene soot particles also had strong, solid-state free-radical character in electron spin resonance analysis. Spin-trapping studies indicated that fresh butadiene soot in a buffered aqueous solution containing dimethylsulfoxide (DMSO) oxidized the DMSO, leading to CH(3)* radical formation. Butadiene soot DMSO extract (BSDE)-exposed NHBE cells displayed extranuclear fluorescence within 4 hr of exposure. BSDE was cytotoxic to > 20% of the cells at 72 hr. Morphologic alterations, including cell swelling and membrane blebbing, were apparent within 24 hr of exposure. These alterations are characteristic of oncosis, an ischemia-induced form of cell death. BSDE treatment also produced significant genotoxicity, as indicated by binucleated cell formation. The combination of moderate cytotoxicity and genotoxicity, as occurred here, can be pro-carcinogenic.