tbuckley/cabot-search huggingface dataset:
Renal Papillary Necrosis and Analgesics
Authors: Benedict R. Harrow
Journal: JAMA (1963)

In many instances renal papillary necrosis (RPN) can be diagnosed with confidence on the basis of typical x-ray patterns. Three cases of RPN following phenacetin abuse are reported from private practice, indicating that phenacetin addiction with resultant renal damage may not be rare in the United States. Establishing the presence of RPN has become important clinically because of the following reasons: (1) Renal destruction in phenacetin habitues can be arrested by discontinuing the drug. (2) Recognition of RPN in diabetic patients makes possible vigorous, lengthy antimicrobial therapy resulting in prolonged and useful lives. (3) In a few acute, unilateral cases nephrectomy may be life-saving. (4) Ability to recognize the disease on x-rays allows search for other drugs that could cause the necrosis. The authors have found that the medullary form of renal necrosis occurs in sickle-cell disease.
Phase I Study of the Poly(ADP-Ribose) Polymerase Inhibitor, AG014699, in Combination with Temozolomide in Patients with Advanced Solid Tumors
Authors: Ruth Plummer, Christopher Jones, Mark Middleton, Richard Wilson, Jeffrey Evans, Anna Olsen, Nicola Curtin, Alan Boddy, Peter McHugh, David Newell, Adrian Harris, Patrick Johnson, Heidi Steinfeldt, Raz Dewji, Diane Wang, Lesley Robson, Hilary Calvert
Journal: Clinical Cancer Research (2008)

Abstract Purpose: One mechanism of tumor resistance to cytotoxic therapy is repair of damaged DNA. Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme involved in base excision repair, one of the five major repair pathways. PARP inhibitors are emerging as a new class of agents that can potentiate chemotherapy and radiotherapy. The article reports safety, efficacy, pharmacokinetic, and pharmacodynamic results of the first-in-class trial of a PARP inhibitor, AG014699, combined with temozolomide in adults with advanced malignancy. Experimental Design: Initially, patients with solid tumors received escalating doses of AG014699 with 100 mg/m2/d temozolomide × 5 every 28 days to establish the PARP inhibitory dose (PID). Subsequently, AG014699 dose was fixed at PID and temozolomide escalated to maximum tolerated dose or 200 mg/m2 in metastatic melanoma patients whose tumors were biopsied. AG014699 and temozolomide pharmacokinetics, PARP activity, DNA strand single-strand breaks, response, and toxicity were evaluated. Results: Thirty-three patients were enrolled. PARP inhibition was seen at all doses; PID was 12 mg/m2 based on 74% to 97% inhibition of peripheral blood lymphocyte PARP activity. Recommended doses were 12 mg/m2 AG014699 and 200 mg/m2 temozolomide. Mean tumor PARP inhibition at 5 h was 92% (range, 46-97%). No toxicity attributable to AG014699 alone was observed. AG014699 showed linear pharmacokinetics with no interaction with temozolomide. All patients treated at PID showed increases in DNA single-strand breaks and encouraging evidence of activity was seen. Conclusions: The combination of AG014699 and temozolomide is well tolerated, pharmacodynamic assessments showing proof of principle of the mode of action of this new class of agents.
Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype
Authors: Jill R Storry, Magnus Jöud, Mikael Kronborg Christophersen, Britt Thuresson, Bo Åkerström, Birgitta Nilsson Sojka, Björn Nilsson, Martin L Olsson
Journal: Nature Genetics (2013)
Immunomodulation by mucosal gene transfer using TGF-beta DNA.
Authors: N A Kuklin, M Daheshia, S Chun, B T Rouse
Journal: Journal of Clinical Investigation (1998)

This report evaluates the efficacy of DNA encoding TGF-beta administered mucosally to suppress immunity and modulate the immunoinflammatory response to herpes simplex virus (HSV) infection. A single intranasal administration of an eukaryotic expression vector encoding TGF-beta1 led to expression in the lung and lymphoid tissue. T cell-mediated immune responses to HSV infection were suppressed with this effect persisting as measured by the delayed-type hypersensitivity reaction for at least 7 wk. Treated animals were more susceptible to systemic infection with HSV. Multiple prophylactic mucosal administrations of TGF-beta DNA also suppressed the severity of ocular lesions caused by HSV infection, although no effects on this immunoinflammatory response were evident after therapeutic treatment with TGF-beta DNA. Our results demonstrate that the direct mucosal gene transfer of immunomodulatory cytokines provides a convenient means of modulating immunity and influencing the expression of inflammatory disorders.
Suspended animation inducer hydrogen sulfide is protective in an in vivo model of ventilator-induced lung injury
Authors: Hamid Aslami, André Heinen, Joris J. T. H. Roelofs, Coert J. Zuurbier, Marcus J. Schultz, Nicole P. Juffermans
Journal: Intensive Care Medicine (2010)

Acute lung injury is characterized by an exaggerated inflammatory response and a high metabolic demand. Mechanical ventilation can contribute to lung injury, resulting in ventilator-induced lung injury (VILI). A suspended-animation-like state induced by hydrogen sulfide (H₂S) protects against hypoxia-induced organ injury. We hypothesized that suspended animation is protective in VILI by reducing metabolism and thereby CO₂ production, allowing for a lower respiratory rate while maintaining adequate gas exchange. Alternatively, H₂S may reduce inflammation in VILI.In mechanically ventilated rats, VILI was created by application of 25 cmH₂O positive inspiratory pressure (PIP) and zero positive end-expiratory pressure (PEEP). Controls were lung-protective mechanically ventilated (13 cmH₂O PIP, 5 cmH₂O PEEP). H(2)S donor NaHS was infused continuously; controls received saline. In separate control groups, hypothermia was induced to reproduce the H₂S-induced fall in temperature. In VILI groups, respiratory rate was adjusted to maintain normo-pH.NaHS dose-dependently and reversibly reduced body temperature, heart rate, and exhaled amount of CO₂. In VILI, NaHS reduced markers of pulmonary inflammation and improved oxygenation, an effect which was not observed after induction of deep hypothermia that paralleled the NaHS-induced fall in temperature. Both NaHS and hypothermia allowed for lower respiratory rates while maintaining gas exchange.NaHS reversibly induced a hypometabolic state in anesthetized rats and protected from VILI by reducing pulmonary inflammation, an effect that was in part independent of body temperature.
STUDIES IN RODENT POLIOMYELITIS
Authors: Claus W. Jungeblut
Journal: The Journal of Experimental Medicine (1945)

1. Attempts to separate by processes of physical segregation, i.e. ultrafiltration, ultracentrifugation, or dialysis, from live SK murine poliomyelitis virus a non-pathogenic agent capable of interfering with simian poliomyelitis virus were unsuccessful. Neither was it possible to convert live SK murine virus into a non-pathogenic interfering agent by processes of chemical inactivation, i.e., phenolization or formalinization. 2. Preparations of SK murine virus, which had been markedly attenuated by ultraviolet irradiation, gave evidence of having retained some interfering power in rhesus monkeys. 3. MM murine poliomyelitis virus interfered, both in mixture tests and by peripheral administration, with two simian strains of poliomyelitis virus. With adequate amounts, distinct protective effects could be obtained in rhesus monkeys which had received murine virus (animal passage or tissue culture virus) up to 48 hours after intracerebral infection with simian poliomyelitis virus. 4. Theiler's virus of spontaneous mouse encephalomyelitis, when tested in mixture with simian poliomyelitis virus, gave some evidence of irregular and low grade interference. Interference could not be shown conclusively in experiments to prevent poliomyelitic infection or to modify its effects. 5. The nature of the interfering agent present in murine virus is discussed.
Coexistence of bullous pemphigoid and pemphigus foliaceus
Authors: CHRISTINE I. HARRINGTON, I.B. SNEDDON
Journal: British Journal of Dermatology (1979)

Journal Article Coexistence of bullous pemphigoid and pemphigus foliaceus Get access CHRISTINE I. HARRINGTON, CHRISTINE I. HARRINGTON Rupert Hallam Department of Dermatology, Hallamshire Hospital, Glossop Road, Sheffield Search for other works by this author on: Oxford Academic Google Scholar I.B. SNEDDON I.B. SNEDDON Rupert Hallam Department of Dermatology, Hallamshire Hospital, Glossop Road, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 100, Issue 4, 1 April 1979, Pages 441–445, https://doi.org/10.1111/j.1365-2133.1979.tb01647.x Published: 01 April 1979
Ruptured abdominal aortic aneurysm presenting with ureteric colic.
Authors: D O'Donnell
Journal: BMJ (1987)

SIR,-The article byMrCG Moran and colleagues (16 May, p 1279) acknowledges the difficulty of establishing the diagnosis of ruptured aortic aneurysm and highlights the trap of ureteric colic. Experience at Royal Perth Hospital supports this. This hospital's experience ofpatients with acute renal failure requiring dialysis after repair of abdominal aortic aneurysm has recently been examined. In 29 of 33 such patients surgery followed emergency presentation. Seven of these patients reported symptoms that suggested a diagnosis ofureteric colic, and in four cases pain in or radiating to the testis indicated a ureteric origin. The finding of microscopic haematuria was considered further evidence for this. Back pain was a major symptom in seven other patients, and three patients were being investigated for renal or spinal disease when sudden hypotension or severe abdominal pain, or both, redirected the investigation. Ruptured abdominal aortic aneurysm merits a prominent position in the differential diagnosis of ureteric colic in older patients. For the reasons outlined by Mr Moran and colleagues, the finding of microsopic haematuria should not exclude rupture of an aneurysm from consideration. DAN O'DONNELL
Uremic pericarditis as a cause of cardiac tamponade.
Authors: J J Baldwin, J E Edwards
Journal: Circulation (1976)

Uremic pericarditis may complicate either acute or, more commonly, chronic renal failure. When dialysis is not employed, uremic pericarditis is usually a preterminal event and is characterized by a serofibrinous exudation of an amount inadequate to cause cardiac tamponade. Nevertheless, cardiac tamponade may uncommonly be observed in nondialyzed patients. Cardiac tamponade, which may be life-threatening, is more common in dialyzed than in nondialyzed patients with chronic renal failure. The primary causes of cardiac tamponade in uremic pericarditis in order of decreasing frequency are (1) pericardial effusion, usually of the serosanguineous type, (2) massive hemorrhage into the pericardial sac and (3) collagenization of pericardial exudate. From pathologic evidence, the following forms of therapy appear appropriate to manage uremic pericarditis that has reached the stage of causing cardiac tamponade. For effusion, pericardiocentesis or parietal pericardiectomy are logical procedures. Massive hemorrhage into the pericardial sac is usually attended by clotting and requires pericardiotomy and evacuation of clot. Collagenization of exudate yields an encasing, fibrous shell over the heart and requires decortication, as is practised in classical constrictive pericarditis.
Abstract 2195: Scribble-mediated membrane targeting of PHLPP1 is required for its tumor suppressor function
Authors: Xin Li, Tianyan Gao
Journal: Cancer Research (2011)

Abstract PHLPP1 is a Ser/Thr protein phosphatase that serves as a tumor suppressor by negatively regulating Akt. Here, we show that PHLPP1 is recruited to the basolateral membrane in colon cancer cells by binding to a scaffolding protein Scribble (Scrib). A small region in the C-terminus of PHLPP1 and the leucine-rich repeat (LRR) domain of Scrib are required for their interaction. Knockdown of Scrib results in a redistribution of PHLPP from the membrane to the cytoplasm, whereas overexpression of Scrib has the opposite effect. Furthermore, PHLPP1-dependent dephosphorylation of Akt is facilitated by the formation of Scrib, PHLPP1, and Akt trimeric complex in cells. IHC staining of human tissues reveals an identical localization pattern of PHLPP1 and Scrib in normal colonic epithelia, whereas downregulation or mislocalization of PHLPP1 and Scrib is observed in colorectal cancers. Taken together, our findings identify a functional interaction between PHLPP1 and Scrib in negatively regulating Akt signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2195. doi:10.1158/1538-7445.AM2011-2195
662. Retroviral Insertion Site Analysis Following Therapeutic Gene Transfer of CD18 in a Canine Model of Leukocyte Adhesion Deficiency
Authors: Mehreen Hai, Thomas R. Bauer, Laura M. Tuschong, Yuchen Gu, Robert A. Sokolic, Dennis D. Hickstein
Journal: Molecular Therapy (2006)

Retroviral insertion site analysis following the infusion of gene-corrected hematopoietic stem cells has become increasingly important following the development of leukemia in three children with common γ-chain severe combined immunodeficiency treated with retroviral gene therapy. This analysis is of particular importance in human gene therapy trials and in gene-transfer studies in disease- specific, large-animal models. We have conducted pre-clinical gene therapy in canine leukocyte adhesion deficiency (CLAD), the canine equivalent of leukocyte adhesion deficiency, type 1 (LAD-1) in humans. Both diseases are characterized by life-threatening bacterial infections and are due to mutations in the leukocyte integrin CD18. We have demonstrated reversal of the disease phenotype in six dogs with CLAD following infusion of autologous CD34+ bone marrow hematopoietic stem cells transduced with the retroviral vector PG13/ MSCV-cCD18 after non-myeloablative conditioning with either 200 cGy TBI or 10 mg/kg busulfan. In the six CLAD dogs who were long-term survivors, the level of CD18+ gene corrected leukocytes ranged from 0.72% to 8.37% at 1–1.5 years post-transplant. Although no adverse events have occurred during this period of observation, demonstration of polyclonality in the gene-corrected cells and characterization of the genomic sites of retroviral integration remain critical safety issues. To this end, we have demonstrated the polyclonality of contributing retrovirus-transduced cells in all six dogs using linear-amplification mediated PCR (LAM-PCR) with DNA obtained from peripheral blood leukocytes up to 18 months following infusion of gene-corrected cells. Multiple clones were shown to contribute to hematopoiesis; no predominant clones emerged over time. Retroviral insertion sites in four of the six dogs were identified using either LAM-PCR or ligation-mediated PCR (LM-PCR) followed by sequencing of the genomic sequence adjacent to the integrated viral LTR. Mapping of insertion sites was facilitated by the recent completion of the annotated dog genome sequence. To date, we have identified 60 unique retroviral insertion sites from four treated CLAD dogs. The insertions sites appear to be distributed almost equally across all 39 dog chromosomes, with a slight preference for chromosomes 2, 10 and 25. 43% of the sites were located within gene-coding regions of the genome (introns or exons). These observations match previous reports of preferential integration of MLV retroviral vectors near coding sequences. We are continuing to sequence and characterize a large number of retroviral insertion sites from the gene-corrected CLAD dogs. Analysis of these insertion sites should provide considerable insight into the risk of genotoxicity through insertional mutagenesis in a disease-specific large-animal model of a human hematopoietic disease.
Eight-year outcomes of the Childhood Asthma Prevention Study
Authors: Brett G. Toelle, Kitty K.W. Ng, Daniele Crisafulli, Elena G. Belousova, Catarina Almqvist, Karen Webb, Euan R. Tovey, Andrew S. Kemp, Craig M. Mellis, Stephen R. Leeder, Guy B. Marks
Journal: Journal of Allergy and Clinical Immunology (2010)
Autopsy Diagnosis of Legionnaires' Disease in Immunosuppressed Patients
Authors: J. K. FRENKEL
Journal: Annals of Internal Medicine (1979)

A diffuse pneumonia characterized by short Giemsa-stained, gram-negative rods that were not cultured was diagnosed at autopsy in the fall of 1975 in three immunosuppressed patients who had had renal transplants. An acute fibrinous exudate was found, with macrophages, neutrophils, and numerous short bacilli in each inflamed alveolus as shown by Giemsa's stain (Wohlbach modification). Transplantation was stopped for 1 month. The institutional infection control committee discussed the cases, and increased observation. After the Legionnaires' disease agent was identified in 1977, the bacteria were stained by Dieterle's method and identified as Legionnaires' disease bacteria by direct fluorescent antibody test. No further cases have been identified in the succeeding 62 renal transplantations at this medical center. Although Wohlbach's modification of Giemsa has given consistently good staining of the Legionnaires' disease bacterium in our cases, unclarified factors may interfere with good staining, and the May-Grünwald Giemsa stain was unsatisfactory.
The End of Managed Care
Authors: James C. Robinson
Journal: JAMA (2001)

Managed care embodies an effort by employers, the insurance industry, and some elements of the medical profession to establish priorities and decide who gets what from the health care system. After a turbulent decade of trial and error, that experiment can be characterized as an economic success but a political failure. The strategy of giving with one hand while taking away with the other, of offering comprehensive benefits while restricting access through utilization review, has infuriated everyone involved. The protagonists of managed care now are in full retreat, broadening physician panels, removing restrictions, and reverting to fee-for-service payment. Governmental entities are avoiding politically volatile initiatives to balance limited resources and unlimited expectations. By default, if not by design, the consumer is emerging as the locus of priority setting in health care. The shift to consumerism is driven by a widespread skepticism of governmental, corporate, and professional dominance; unprecedented economic prosperity that reduces social tolerance for interference with individual autonomy; and the Internet technology revolution, which broadens access to information and facilitates the mass customization of insurance and delivery.
Increased FDG Activity in a Dermatofibroma in Esophageal Cancer Patient
Authors: Brigid A. Bingham, Daniel A. Hatef, Patricia Chevez-Barrios, Shanda H. Blackmon, Min P. Kim
Journal: Clinical Nuclear Medicine (2013)

PET using the radiotracer 18F-FDG is used for staging patients with esophageal cancer. Nonmalignant conditions, mainly inflammation and some benign tumors, however, can cloud the clinical picture by taking up FDG and producing a false-positive result. We report the case of a 46 year-old man with squamous cell carcinoma of the thoracic esophagus who underwent combined PET/CT and had false-positive uptake in a chest wall dermatofibroma. Dermatofibroma is a benign skin lesion with a characteristic large presence of fibroblasts and macrophages. Macrophage uptake of FDG is likely responsible for the false-positive result on PET/CT.
Dr. Thomas Hodgkin's Friendship with Sir Moses Montefiore
Authors: Amalie M. Kass
Journal: New England Journal of Medicine (1984)

Few men in Victorian England presented greater contrasts than the Quaker physician Dr. Thomas Hodgkin and the Jewish financier Sir Moses Montefiore, yet for more than 40 years, they were remarkably good friends. Hodgkin's role as physician to various members of the Montefiore family was the basis for their acquaintance, but beneath the professional relationship lay a strong concern that each felt for the oppressed. This shared commitment forged their friendship, produced joint philanthropic activities in England, and led to five overseas journeys made for the relief of suffering Jews. The bicentenary/centenary anniversary of Sir Moses Montefiore (1784–1885) recalls that . . .
Second Attacks of Measles.
Authors: I. N. Brainard
Journal: JAMA (1898)

ABSTRACT Alma, Mich., May 17, 1898.To the Editor: —Some weeks ago, I saw in the Journal a communication from some one setting forth, tentatively, the theory that a second-time case of measles will not communicate measles. Six weeks ago Effie G. was taken sick with measles the second time. In the same family is a child of four years who never had measles. She remained in the room with the sick girl nearly all the time, and did not take the disease. If this is the principle in these cases it should be known.Yours,
Role of Lysosomes in the Pathogenesis of Splanchnic Ischemia Shock in Cats
Authors: THOMAS M. GLENN, ALLAN M. LEFER
Journal: Circulation Research (1970)

Splanchnic arterial occlusion (SAO) for 2 hours followed by release of the occlusion in cats produced a lethal shock state characterized by cardiovascular collapse. Release of the occlusion resulted in a 45% fall in mean arterial blood pressure within 15 minutes; postrelease survival of these animals was 46 minutes. The plasma of cats with SAO shock exhibited a 3- to 4-fold increase in activities of the lysosomal enzymes β-glucuronidase and cathepsin, accompanied by accumulation of a myocardial depressant factor. Plasma from cats treated with methylprednisolone (20 mg/kg) prior to occlusion did not have significant levels of myocardial depressant factor nor significant increases in plasma lysosomal enzyme activity. Furthermore, the fall in mean arterial blood pressure in steroid-treated animals was significantly smaller when the occlusion was released and postrelease survival time was significantly longer. Pancreatic lysosomes from cats with SAO exhibited a marked increase in fragility as indicated by a reduction in total lysosomal enzyme activity and an increase in the percent of free enzyme activity, compared to lysosomes from cats with sham SAO or steroid-treated cats. These data indicate that the biochemical and hemodynamic alterations present in SAO-induced shock may be related to the disruption of pancreatic lysosomes and that glucocorticoids can markedly alter the course of this shock, possibly by decreasing the sensitivity of pancreatic lysosomes to splanchnic ischemia.
BLOOD FROM THE DEAD FOR TRANSFUSIONS
Authors: WILLIAM H. WALSH
Journal: Annals of Internal Medicine (1935)

Editorial1 April 1935BLOOD FROM THE DEAD FOR TRANSFUSIONSWILLIAM H. WALSHWILLIAM H. WALSHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-8-10-1375 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOne of the most perplexing problems to hospitals and to the medical profession is the difficulty of securing blood for transfusions in sufficient quantities at all times and at a cost within the reach of people of limited means who need it.Under existing conditions the procedure of transfusion is available for use only when the patient is able to pay for a donor, or when a voluntary donor is available, or when the cost can be met from charitable funds. Not infrequently none of these avenues are open and a patient urgently needing transfusion must do without.To meet...1 JUDIN S: La transfusion du sang de cadavre à l'homme, Paris, 1933. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1935Volume 8, Issue 10Page: 1375-1377KeywordsBlood transfusion ePublished: 1 December 2008 Issue Published: 1 April 1935 PDF downloadLoading ...