tbuckley/cabot-search huggingface dataset:
No more free lunches: The market has us all in its grip
Authors: K S Madhavan
Journal: BMJ (2003)

EDITOR—The relationship between the pharmaceutical industry and the medical profession is natural and can be constructive and cooperative, as well as dishonourable and damaging.1

Any debate on the influence of marketing on decision making and health outcome is considered to be too doctrinaire to be worth while. The subdued response to the theme issue from hospital practitioners is testimony to their belief that it is futile. The market …
Long haul flights double the risk of thrombosis related to air travel
Authors: John Zarocostas
Journal: BMJ (2007)

Epidemiological studies show that the risk of venous thromboembolism doubles after long haul air travel of more than four hours' duration, a World Health Organization report says.

The final report of phase I of the WHO research into global hazards of travel (WRIGHT) project concludes that the absolute risk of venous thromboembolism among healthy individuals for a flight of more than four hours was 1 in 6000. Pathophysiological studies, it says, support these findings.

The studies were carried out by an international collaboration of researchers from …
Scientific Foundations of Neurology
Authors: William DeMyer
Journal: JAMA (1973)

The editors of this multiauthored volume intended to "highlight some of the more recent work [for] neurologic clinicians or research-workers who are anxious for information as to the scientific principles of their own studies or those of colleagues in cognate fields." The book is divided into major sections, "Physiology in General," "The Peripheral Nervous System," "Motor System," "Epilepsy," "Sensory System," "Higher Nervous Activity," "Cerebral Circulation," "Cerebrospinal Fluid and Intracranial Pressure," "Diagnostic and Therapeutic Techniques," and finally, "Some Interesting Conditions." Each section has chapters by several authors. The editors make no attempt to coordinate or correlate the contributions. Subjects such as neuroradiology, genetics, and developmental or pediatric neurology receive little attention. How well do the editors meet their goals? As to highlighting recent work for specialists in the field, we must challenge several chapters. For example, in "The Nerve Cell and Its Properties," only three of the 21 references were published
Near-Roadway Pollution and Childhood Asthma: Implications for Developing “Win–Win” Compact Urban Development and Clean Vehicle Strategies
Authors: Laura Perez, Fred Lurmann, John Wilson, Manuel Pastor, Sylvia J. Brandt, Nino Künzli, Rob McConnell
Journal: Environmental Health Perspectives (2012)

Background: The emerging consensus that exposure to near-roadway traffic-related pollution causes asthma has implications for compact urban development policies designed to reduce driving and greenhouse gases.Objectives: We estimated the current burden of childhood asthma-related disease attributable to near-roadway and regional air pollution in Los Angeles County (LAC) and the potential health impact of regional pollution reduction associated with changes in population along major traffic corridors.Methods: The burden of asthma attributable to the dual effects of near-roadway and regional air pollution was estimated, using nitrogen dioxide and ozone as markers of urban combustion-related and secondary oxidant pollution, respectively. We also estimated the impact of alternative scenarios that assumed a 20% reduction in regional pollution in combination with a 3.6% reduction or 3.6% increase in the proportion of the total population living near major roads, a proxy for near-roadway exposure.Results: We estimated that 27,100 cases of childhood asthma (8% of total) in LAC were at least partly attributable to pollution associated with residential location within 75 m of a major road. As a result, a substantial proportion of asthma-related morbidity is a consequence of near-roadway pollution, even if symptoms are triggered by other factors. Benefits resulting from a 20% regional pollution reduction varied markedly depending on the associated change in near-roadway proximity.Conclusions: Our findings suggest that there are large and previously unappreciated public health consequences of air pollution in LAC and probably in other metropolitan areas with dense traffic corridors. To maximize health benefits, compact urban development strategies should be coupled with policies to reduce near-roadway pollution exposure.
Lepromatous Leprosy
Authors: Alfred Hollander, Sheldon C. Sommers
Journal: New England Journal of Medicine (1952)

CASES of leprosy (Hansen's disease) are rarely seen in New England. For this reason we believe it worth while to report a case of lepromatous leprosy. The physician unfamiliar with the symptoms of the disease is unlikely to make the proper diagnosis since he is not aware of the possibility of encountering this rare malady.Clinical classification of the different types of leprosy is difficult. The International LeprosyCongress of Cairo,1 in 1938, accepted the classification of lepromatous (cutaneous), neural and mixed types of leprosy. The International Leprosy Congress of Havana, Cuba,2 in 1948, adopted the division of cases into . . .
Adenosine triphosphate citrate lyase mediates hypocitraturia in rats.
Authors: J Z Melnick, P A Srere, N A Elshourbagy, O W Moe, P A Preisig, R J Alpern
Journal: Journal of Clinical Investigation (1996)

Chronic metabolic acidosis increases proximal tubular citrate uptake and metabolism. The present study addressed the effect of chronic metabolic acidosis on a cytosolic enzyme of citrate metabolism, ATP citrate lyase. Chronic metabolic acidosis caused hypocitraturia in rats and increased renal cortical ATP citrate lyase activity by 67% after 7 d. Renal cortical ATP citrate lyase protein abundance increased by 29% after 3 d and by 141% after 7 d of acid diet. No significant change in mRNA abundance could be detected. Hypokalemia, which causes only intracellular acidosis, caused hypocitraturia and increased renal cortical ATP citrate lyase activity by 28%. Conversely, the hypercitraturia of chronic alkali feeding was associated with no change in ATP citrate lyase activity. Inhibition of ATP citrate lyase with the competitive inhibitor, 4S-hydroxycitrate, significantly abated hypocitraturia and increased urinary citrate excretion fourfold in chronic metabolic acidosis and threefold in K+-depletion. In summary, the hypocitraturia of chronic metabolic acidosis is associated with an increase in ATP citrate lyase activity and protein abundance, and is partly reversed by inhibition of this enzyme. These results suggest an important role for ATP citrate lyase in proximal tubular citrate metabolism.
Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.
Authors: D A Maddox, F J Gennari
Journal: Journal of Clinical Investigation (1983)

Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary PCO2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHCO3. Proximal tubular bicarbonate reabsorption and PCO2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A group of nine age-matched control animals, fed the same diet but not given furosemide, was studied for comparison. In a third group of controls, the filtered load of bicarbonate was varied over the same range as in the CMA rats by plasma infusion and aortic constriction. The CMA rats had significant alkalemia and hypokalemia (4-7 d: pH 7.58, HCO3 38.3 meq/liter, K+ 2.1 meq/liter; 11-14 d: pH 7.54, HCO3 38.1 meq/liter, K+ 2.5 meq/liter). Nonetheless, proximal bicarbonate reabsorption was not significantly different from that seen in control rats at any given load of filtered bicarbonate (from 250 to 1,300 pmol/min). In both control and CMA rats, 83-85% of the filtered bicarbonate was reabsorbed by the end of the accessible proximal tubule. These observations indicate that proximal bicarbonate reabsorption is determined primarily by the filtered load in chronic metabolic alkalosis. When single nephron glomerular filtration rate (SNGFR) is reduced by volume depletion in the early postfurosemide period, the filtered load and the rate of proximal bicarbonate reabsorption remain at or below control levels, maintaining metabolic alkalosis. In the late postfurosemide period, however, SNGFR returned to control levels in some instances. In these animals, both the filtered load and rate of proximal reabsorption were increased above the highest levels seen in control animals. The PCO2 gradient between the peritubular capillaries and arterial blood (Pc-Art) was significantly higher in CMA than in control, even though the rate of proximal bicarbonate reabsorption did not differ. Thus, proximal bicarbonate reabsorption did not appear to be the primary determinant of Pc-Art PCO2. PCO2 in the early proximal (EP) tubule was significantly higher than in either the late proximal (LP) tubule or peritubular capillaries in both control and CMA rats. The EP-LP PCO2 gradient correlated directly with proximal bicarbonate reabsorption (P less than 0.05). The small elevation in PCO2 in EP may be related to CO2 generated at this site in the process of bicarbonate reabsorption.
Is benzoyl peroxide carcinogenic?
Authors: S. Liden, B. Lindelof, P. Sparen
Journal: British Journal of Dermatology (1990)

Journal Article Is benzoyl peroxide carcinogenic? Get access S. Lidén, S. Lidén Department of Dermatology, Karolinska Hospital, S‐10401 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar B. Lindelof, B. Lindelof Department of Dermatology, Karolinska Hospital, S‐10401 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar P. Sparén P. Sparén The Swedish Cancer Registry, The National Board of Health and Welfare, S‐106 30 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 1, 1 July 1990, Page 129, https://doi.org/10.1111/j.1365-2133.1990.tb01836.x Published: 01 July 1990
Replacement of the Femoral Head in Severe Osteoarthritis of the Hip
Authors: John G. Kuhns, Theodore A. Potter, W. A. Elliston, Robert S. Hormell
Journal: New England Journal of Medicine (1952)

THE pain and disability in severe osteoarthritis of the hip joint are often not relieved by conservative measures.1 In these severely damaged joints surgical procedures have been employed with increasing frequency. The surgical measures can be divided into five types: operations to improve the circulation2 in the femoral head and neck,3 operations to denervate the articular capsule of the hip joint,4 operations to stop all motion5 at the hip joint,6 operations to change the line of weight bearing coming through the hip joint7 and operations to improve motion by removing the bony proliferation8 about the femoral head and acetabulum, at . . .
Abstract 4153: Arrayed microinjection of a ubiquitin activating enzyme inhibitor induces PD biomarker effects predictive of <i>in vivo</i> tumor responses to systemic drug delivery.
Authors: Beryl A. Hatton, Marc Grenley, Nathan Hedin, Nathan Caffo, Marc L. Hyer, Mark Manfredi, Stephen Blakemore, Richard A. Klinghoffer, Neil Bence
Journal: Cancer Research (2013)

Abstract Presage technology enables simultaneous analysis of multiple cancer drug candidates, drug concentrations, and drug combinations within a single living tumor. The platform employs arrayed tumor microinjection technology that delivers multiple spatially defined “threads” of drug directly into discreet portions of a tumor. This enables rapid, reliable, and internally controlled cross comparisons of multiple cancer therapeutics using screening quantities of drug in an in vivo setting in which the local tumor microenvironment is maintained. Here, as an example, we apply the platform to investigate tumor responsiveness to an inhibitor of the ubiquitin activating enzyme UBA1 from Millennium Pharmaceuticals. The ubiquitin activating enzyme UBA1 regulates ubiquitin activation and subsequent polyubiquitination of proteins necessary for their degradation by the proteasome, and functionally impacts cell signaling, DNA damage repair and cell cycle progression. In vivo tumor responses were evaluated in two human xenograft models, WSU-DLCL2 and MCF-7, grown as flank tumors in immune-compromised mice. Microdosing of multiple concentrations of the UBA1 inhibitor (UBAi) into both models led to localized, easily detectable, and drug concentration-dependent biomarker changes indicative of ubiquitin pathway perturbation in the area proximal to injected drug. This included loss of poly-ubiquitin, accompanied by the expected accumulation of cMyc in tumor regions exposed to the UBAi. Localized time-dependent tumor cell death responses were observed following pathway perturbation as quantified by staining for cleaved caspase-3 and gamma-H2AX staining. Furthermore, pathological evidence of UBAi-induced cell death was clearly visible in both tumor models upon histological examination of H&amp;E stained slides. These results highlight the capacity of the Presage platform to perform multiplexed drug studies in live tumor models. This capability could readily be expanded for use in validating additional biomarker hypotheses, indication finding studies, or for efficient identification of novel drug combinations. Citation Format: Beryl A. Hatton, Marc Grenley, Nathan Hedin, Nathan Caffo, Marc L. Hyer, Mark Manfredi, Stephen Blakemore, Richard A. Klinghoffer, Neil Bence. Arrayed microinjection of a ubiquitin activating enzyme inhibitor induces PD biomarker effects predictive of in vivo tumor responses to systemic drug delivery. [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 4153. doi:10.1158/1538-7445.AM2013-4153
Familial Atrial Myxoma
Authors: MICHEL G. FARAH
Journal: Annals of Internal Medicine (1975)

Two siblings 14 years apart were found to have atrial myxomas. The brother's right atrial myxoma was found at age 21 and his sister's left atrial myxoma, with peripheral cerebral and coronary aneurysms, at age 30. Both tumors were excised successfully. These findings support previous reports suggesting that atrial myxoma may be familial. Echocardiography can be used effectively in the diagnosis of atrial myxoma, detection of its possible recurrence, and screening other members of the family.
Iron-Chelating Agents in Non-Iron Overload Conditions
Authors: E. E. Voest
Journal: Annals of Internal Medicine (1994)

Purpose: To review the current clinical experience with iron chelators in non-iron overload conditions. Data Sources: The English-language literature was searched from 1983 through 1992 manually and using MEDLINE. Study Selection: Original articles, case reports, and abstracts addressing iron chelation. Data Extraction: Selected reports that described clinical applications of iron chelators in non-iron overload conditions were classified according to their stated mechanism of interference with disease activity. Articles stating the rationale for clinical use of iron chelators were also included. Results: Iron chelators were used in non-iron overload conditions to produce antioxidant effects, antiproliferative effects, and antiprotozoal effects and for aluminum chelation. In addition, several reports described singular observations in various diseases. Deferoxamine is the only iron chelator available for clinical studies. The treatment-related (side) effects appear to be associated with patient iron levels. Conclusions: Randomized clinical trials are needed to confirm the promising effects of iron chelators in non-iron overload conditions. Oral iron chelators with fewer toxic effects are especially needed.
Utility of Currently Recommended Pediatric Dyslipidemia Classifications in Predicting Dyslipidemia in Adulthood
Authors: Costan G. Magnussen, Olli T. Raitakari, Russell Thomson, Markus Juonala, Dharmendrakumar A. Patel, Jorma S.A. Viikari, Jukka Marniemi, Sathanur R. Srinivasan, Gerald S. Berenson, Terence Dwyer, Alison Venn
Journal: Circulation (2007)

Background— New age- and sex-specific lipoprotein cut points developed from National Health and Nutrition Examination Survey (NHANES) data are considered to be a more accurate classification of a high-risk lipoprotein level in adolescents compared with existing cut points established by the National Cholesterol Education Program (NCEP). The aim of this study was to determine which of the NHANES or NCEP adolescent lipoprotein classifications was most effective for predicting abnormal levels in adulthood. Methods and Results— Adolescent and adult measures of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were collected in 365 Australian, 1185 Finnish, and 273 US subjects participating in 3 population-based prospective cohort studies. Lipoprotein variables in adolescence were classified according to NCEP and NHANES cut points and compared for their ability to predict abnormal levels in adulthood. With the use of diagnostic performance statistics (sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic curve) in pooled and cohort-stratified data, the NHANES cut points (compared with NCEP cut points) were more strongly predictive of low high-density lipoprotein cholesterol in adults but less predictive of high total cholesterol, high low-density lipoprotein cholesterol, and high triglyceride levels in adults. We identified heterogeneity in the relative usefulness of each classification between cohorts. Conclusions— The separate use of NHANES cut points for high-density lipoprotein cholesterol and NCEP cut points for total cholesterol, low-density lipoprotein cholesterol, and triglycerides yielded the most accurate classification of adolescents who developed dyslipidemia in adulthood.
Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction
Authors: Jens Jakob Thune, James E. Signorovitch, Lars Kober, John J.V. McMurray, Karl Swedberg, Jean Rouleau, Aldo Maggioni, Eric Velazquez, Robert Califf, Marc A. Pfeffer, Scott D. Solomon
Journal: European Journal of Heart Failure (2010)
Efficient major histocompatibility complex class II-restricted presentation of measles virus relies on hemagglutinin-mediated targeting to its cellular receptor human CD46 expressed by murine B cells.
Authors: D Gerlier, M C Trescol-Biémont, G Varior-Krishnan, D Naniche, I Fugier-Vivier, C Rabourdin-Combe
Journal: The Journal of Experimental Medicine (1994)

Measles virus after binding to its cell surface human CD46 receptor fuses with the plasma membrane. This fusion results in envelope hemagglutinin (H) and fusion glycoprotein (F) incorporated into the plasma membrane and injection of the nucleocapsid made of nucleoprotein (NP) into the cytosol. The influence of targeting measles virus (MV) to CD46 in the processing and presentation of MV H and NP to antigen specific MHC class II I-E(d)- and I-A(d)-restricted T cell hybridomas was explored using murine M12-CD46 B cell transfectants. Parent M12 cells, which lack any MV receptor, were unable to present any of these two viral proteins when incubated with MV particles. Incubating M12.CD46 cells with 200 ng and 10 micrograms of MV could strongly stimulate H-specific and NP-specific T cells, respectively. Neosynthesis of MV proteins was not necessary since the efficiency of antigen presentation was similar when using ultraviolet-inactivated MV. Similar enhancing effects (more than 1,000-fold) on antigen presentation were also observed when using purified native H soluble or incorporated into liposomes whereas denaturating H glycoprotein resulted in a poor efficiency in T cell stimulation, M12.CD46 being no more potent than the parental M12 counterpart. MV H and NP presentation efficiency did not depend on MV fusion with plasma membrane as revealed by the lack of effect of specific fusion inhibitors. Both MV H and NP presentations were sensitive to chloroquine inhibition indicating that antigens from CD46-mediated captured MV were likely processed in the endosome/lysosome compartment. Altogether these data indicate that (a) MV targeting via CD46 has a strong effect on the efficiency of antigen presentation by MHC class II, (b) the effect is mediated by the binding of H to CD46, and (c) though MV does fuse with plasma membrane, endocytosis, and processing of virus particles are also occurring. Since, in humans, CD46 is expressed in almost every tissue including professional antigen-presenting cells, such a targeting is likely to play a crucial role in the CD4+ T cell-mediated primary immune response against the pathogen in vivo.
Dating the Origin of the African Human T-Cell Lymphotropic Virus Type-I (HTLV-I) Subtypes
Authors: S. Van Dooren, M. Salemi, A.-M. Vandamme
Journal: Molecular Biology and Evolution (2001)

To investigate the origin of the African PTLV-I virus, we phylogenetically analyzed the available HTLV-I and STLV-I strains. We also attempted to date the presumed interspecies transmissions that resulted in the African HTLV-I subtypes. Molecular-clock analysis was performed using the Tamura-Nei substitution model and gamma distributed rate heterogeneity based on the maximum-likelihood topology of the combined long-terminal-repeat and env third-codon-position sequences. Since the molecular clock was not rejected and no evidence for saturation was found, a constant rate of evolution at these positions for all 33 HTLV-I and STLV-I strains was reasonably assumed. The spread of PTLV-I in Africa is estimated to have occurred at least 27,300 ± 8,200 years ago. Using the available strains, the HTLV-If subtype appears to have emerged within the last 3,000 years, and the HTLV-Ia, HTLV-Ib, HTLV-Id, and HTLV-Ie subtypes appear to have diverged between 21,100 and 5,300 years ago. Interspecies transmissions, most probably simian to human, must have occurred around that time and probably continued later. When the synonymous and nonsynonymous substitution ratios were compared, it was clear that purifying selection was the driving force for PTLV-I evolution in the env gene, irrespective of the host species. Due to the small number of strains in some of the investigated groups, these data on selective pressure should be taken with caution.
MATCH AND MATCH-BOX DERMATITIS
Authors: ROBERT KLABER
Journal: British Journal of Dermatology (1938)

Journal Article MATCH AND MATCH‐BOX DERMATITIS Get access ROBERT KLABER, M.D.Lond., M.R.C.P. ROBERT KLABER, M.D.Lond., M.R.C.P. Physician for Skin Diseases, Prince of Wales's General Hospital; A Chief Assistant, Skin‐Department, St. Bartholomew's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 50, Issue 8-9, 1 August 1938, Pages 451–461, https://doi.org/10.1111/j.1365-2133.1938.tb10592.x Published: 01 August 1938