tbuckley/cabot-search huggingface dataset:
Gastric mucosal damage in sepsis--effects of pretreatment with a synthetic prostaglandin E1 analogue.
Authors: S Arvidsson, K Falt, U Haglund
Journal: Gut (1985)

An experimental model was used which includes intragastric instillation of 80 mM HCl and 0.6 ml bile/kg followed by intravenous infusion of live E coli in cats for up to three hours. This procedure regularly induces gastric mucosal ulcerations. Mucosal blood flow was measured by microspheres before, early, and late in sepsis. Total gastric blood flow was recorded electromagnetically. Mucosal regeneration capacity as reflected by the RNA/DNA ratio was measured. Misoprostol (a PGE1 analogue) was infused iv (5 micrograms/kg X h) or given locally in the stomach (10 micrograms/kg) before bacteriemia. Misoprostol did not influence the haemodynamic response to bacteria. The gastric mucosal damage was assessed either as an index representative for the entire corpus-fundus region or as the number of areas with intact surface epithelium within the series. Misoprostol iv protected the mucosa from ulceration compared with untreated septic controls while misoprostol intragastrically significantly reduced the number of damaged areas only. Topical misoprostol increased total gastric and mucosal blood flows early in sepsis compared to iv or no pretreatment while no difference was seen during late sepsis. The protective effect of misoprostol was thus not dependent on increased gastric mucosal blood flow. Nor was it mediated through effects on mucosal nucleic acid concentrations or ratio.
Inotropic response of stunned hypertrophied myocardium: responsiveness of hypertrophied and normal postischemic isolated rat hearts to calcium and dopamine stimulation
Authors: H Hoffmeister
Journal: Cardiovascular Research (1998)

Severely hypertrophied myocardium was described to have a reduced tolerance towards ischemia. For non-hypertrophied hearts inconclusive findings on the Ca(2+)-responsiveness are reported. Information sensitivity to reversible ischemia and on postischemic Ca(2+)-responsiveness of hearts with clinically common moderate hypertrophy is lacking. Thus, the responsiveness of hypertrophied and normal postischemic myocardium to positive inotropic stimulation should be investigated in the present study.Hearts from spontaneously hypertensive rats (SHR, 4 months old) with significant LV-hypertrophy (+ 50%) and hearts from normotensive 4 months old Wistar rats were investigated using an isovolumic beating isolated heart model (8 hearts/each of the 8 groups). Functional recovery after 30 min of no-flow ischemia was 78 +/- 1% and 77 +/- 3% of preischemic control data in hypertrophied and non-hypertrophied hearts assessed as developed left ventricular pressure (non-ischemic controls: 95 +/- 2% in hypertrophied and 93 +/- 3% in non-hypertrophied controls). Maximum short-term stimulation with Ca2+ revealed a decreased peak left ventricular pressure of 124 +/- 4% in hypertrophied and 120 +/- 5% in non-hypertrophied postischemic hearts, as compared with non-ischemic controls 138 +/- 3% and 157 +/- 5%, respectively ( p < 0.01). A maximum dose of dopamine stimulated hypertrophied and non-hypertrophied postischemic hearts comparable to Ca2+. Analysing the dose-response curve for Ca(2+)-stimulation, the sensitivity expressed as fraction of the maximum was identical in non-ischemic and postischemic myocardium of hypertrophied and non-hypertrophied ventricles in spite of the reduced peak values.The findings demonstrate that after moderate reversible ischemia the steady-state function is similarly decreased in hypertrophied and non-hypertrophied postischemic myocardium. The maximum response to Ca2+ is significantly reduced in both types of myocardium, while the Ca2+ sensitivity is unchanged. Identical results after maximum dopamine stimulation as after Ca2+ indicate that the releasibility of Ca2+ and the beta-adrenoceptors are not the critical causes for the postischemic dysfunction in hypertrophied or non-hypertrophied myocardium.
Bad medicine: specialisation
Authors: D. Spence
Journal: BMJ (2010)

“You’re too good to be a general practitioner,” someone once told me. I never knew whether this statement was a slight or a compliment. In truth general practice chose me, because of particular personality traits (faults), not the other way round. But generalism is in decline, with the assent of the specialists. Gone is the widely experienced general physician, and general surgeons are replaced by an ever expanding list of “ologists” who now seem to be almost single cell specialists.

This drive to specialism is mirrored across …
From Dietary Glucose to Liver Glycogen: The Full Circle Round
Authors: J D McGarry, M Kuwajima, C B Newgard, D W Foster, J Katz
Journal: Annual Review of Nutrition (1987)

PERSPECTIVES AND SUMMARy  52 HISTORICAL BACKGROUND     53 Physiological Studies . . . . . ... . . . . . . . . ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . ...... . . . . . . .. . . . . . 53 Biochemical Studies . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . .. . . . . . . . . . . . . . . . . 54 EMERGENCE OF THE GLUCOSE PARADOX. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 ATTEMPTS TO RESOLVE THE PARADOX  . . . . . . . . . . .   56 Experiments in Animals. . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . . . . . . .. . . . . . . .... . . . . 57 Experiments in Humans . . . . .     61 A Noninvasive Approach . . . . . . . . . . . . . . . . . . . . .. ... . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .... . . 62 UNRESOLVED PROBLEMS..... .   63 Why Is Glucose Not Used Efficiently by the Liver? ... . . .     63 1s Glucose-6-phosphatase Under Metabolic Control?   66 The Fructose-2, 6-bisphosphate Paradox . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Where Does the Glucose-to-Lactate Conversion Take Place? ... .. . . . . . . . . .. . . . . . . ... . . . 67 Is There an Advantage to the Indirect Pathway? . ......... . .   . . . . . . . . . . . . . . 68 CAN THE OLDER AND NEWER FlNDINGS BE RECONCILED?  68 IN RETROSPECT ..... . . .... . . . . . .   . . . . . . . . . . .   69
Variation in Absorption of NPH Insulin Due to Intramuscular Injection
Authors: Allan Vaag, Aase Handberg, Mogens Lauritzen, Jan Erik Henriksen, Karen Damgaard Pedersen, Henning Beck-Nielsen
Journal: Diabetes Care (1990)

To evaluate the importance of accidental intramuscular injection of NPH insulin, we measured disappearance rates of 125I-labeled NPH insulin (Protaphane) from subcutaneous and intramuscular injection sites in the thighs of 11 insulin-dependent diabetes mellitus patients. Both subcutaneous and intramuscular absorption rates were measured four times in each patient. NPH insulin was absorbed much faster when given intramuscularly than when given subcutaneously (T50% = 5.3 vs. 10.3 h, P &amp;lt; 0.0001). The intrapatient (day-to-day) coefficient of variation (C.V.) of T50% values (C.V. T50%) for subcutaneously injected NPH insulin in this study, where all injections were guided by ultrasound determination of the subcutaneous fat layer, was 18.4%. Intrapatient variation of absorption was significantly lower for subcutaneously than intramuscularly injected NPH insulin (C.V. T50% = 18.4 vs. 29.8%, P &amp;lt; 0.01) and was also lower than interpatient variation for subcutaneously injected insulin (C.V. T50% = 18.4 vs. 50%, P &amp;lt; 0.0001). The faster absorption rate and shorter duration of action, together with the higher day-to-day variation in absorption, led us to conclude that intramuscular injection of NPH insulin should be avoided.
The Normal Microbial Flora
Authors: Philip A. Mackowiak
Journal: New England Journal of Medicine (1982)

CONTROVERSY has surrounded the role of the normal microbial flora in health since the early days of microbiology. Pasteur, for one, hypothesized that the normal flora was essential to life.1 Some years later, his hypothesis was tested and convincingly refuted by Reyniers and others at the Lobund Laboratory, University of Notre Dame, who demonstrated that the germ-free state could be maintained for successive generations in various laboratory animals.2 Metchnikoff, in one of many differences with Pasteur, argued that indigenous microorganisms were antagonists that competed with the host for factors essential to life.3 Metchnikoff's proposal has not been so easily rejected. . . .
Microbial exposure, interferon gamma gene demethylation in naïve T‐cells, and the risk of allergic disease
Authors: P. J. Vuillermin, A‐L. Ponsonby, R. Saffery, M. L. Tang, J. A. Ellis, P. Sly, P. Holt
Journal: Allergy (2009)

The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFNgamma) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFNgamma gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFNgamma gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFNgamma gene of naive T-cells.
P3-134: Sunitinib in combination with gemcitabine plus cisplatin for advanced non–small cell lung cancer (NSCLC): preliminary results from a phase I dose escalation study
Authors: Martin Reck, Norbert Frickhofen, Ulrich Gatzemeier, Heinz-Georg Fuhr, Silvana Lanzalone, Maria J. Lechuga, Erjian Wang, Richard Chao, Enriqueta Felip
Journal: Journal of Thoracic Oncology (2007)
The Role of Sympathectomy in the Treatment of Immersion Foot and Frostbite
Authors: James L. Southworth
Journal: New England Journal of Medicine (1945)

THE term "frostbite" designates the lesions produced by exposure to cold. Short exposure to extremely low temperatures or longer exposure to moderately low temperatures results in similar conditions, although damage appears to be more localized when caused by low-temperature exposures of short duration.1 During World War II many cases have resulted from prolonged soaking of the feet in cold water, hence the term "immersion foot." In this connection White2 draws a distinction between the lesions of immersion foot and those caused by prolonged exposure in southern latitudes coupled with nutritional deficiencies. Many patients with frostbite or immersion foot have late . . .
Detection of EGFR Gene Mutations Using the Wash Fluid of CT-Guided Biopsy Needle in NSCLC Patients
Authors: Hiroki Otani, Shinichi Toyooka, Junichi Soh, Hiromasa Yamamoto, Hiroshi Suehisa, Naruyuki Kobayashi, Hideo Gobara, Hidefumi Mimura, Katsuyuki Kiura, Yoshifumi Sano, Susumu Kanazawa, Hiroshi Date
Journal: Journal of Thoracic Oncology (2008)
Deficient proliferation of myeloid, erythroid, and multipotent progenitor cells in long-term marrow cultures from patients with aplastic anemia treated with immunosuppressive therapy
Authors: Enrique Gómez-Morales, Guadalupe Martínez-Jaramillo, Elizabeth Sánchez-Valle, Ignacio Valencia-Plata, Rosa María Arana-Trejo, Miguel Angel Castro, Javier Pizzuto-Chávez, Hector Mayani
Journal: American Journal of Hematology (1998)

By using Dexter-type long-term marrow cultures (D-LTMC), it has been shown previously that hematopoietic progenitor cells (HPC) from patients with aplastic anemia (AA) have a deficient proliferation in vitro. The studies reported to date, however, have focused exclusively on granulomonocytic progenitors and no information exists on erythroid or multipotent progenitor cells. On the other hand, in such studies, the input progenitor cell numbers were significantly below normal levels, thus suggesting that the rapid disappearance of myeloid progenitor cells from AA D-LTMC could also be due, at least in part, to their reduced number at culture onset. In the present study, we have followed the kinetics of myeloid, erythroid, and multipotent progenitors, from 24 AA patients subjected to immunosuppressive therapy (including patients that achieved complete, partial, or no remission at all), throughout a seven-week culture period. For analysis, we grouped all the patients based on their initial content of all three types of progenitors. Thus, we were able to evaluate separately the kinetics of these cells in D-LTMC from patients with normal and subnormal levels of progenitor cells. At the time of marrow sampling, most patients showed decreased levels of HPC; in fact, only 21%, 8%, and 16% of them showed normal levels of myeloid, erythroid, and multipotent progenitors, respectively. When cultured in D-LTMC, HPC from all AA patients analyzed showed a relatively fast disappearance from the cultures. Indeed, myeloid progenitors could be detected for only six weeks, whereas erythroid and multipotent progenitors disappeared from the cultures after two and one weeks of culture, respectively. In contrast, in normal marrow D-LTMC, myeloid, erythroid, and multipotent progenitors were detected for at least seven, five, and three weeks, respectively. Such a deficient proliferation was observed even in cultures of AA patients that contained normal levels of HPC at culture onset. Interestingly, no correlation was found between HPC proliferation in D-LTMC and response to treatment. Thus, the results of this study indicate the presence of a functional in vitro deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment. Furthermore, this work suggests that such a proliferation deficiency is more pronounced in erythroid and multipotent progenitors than in their myeloid counterparts. Am. J. Hematol. 59:149–155, 1998. © 1998 Wiley-Liss, Inc.
Universities' drug discoveries must aid poor countries, student group says
Authors: Janice Hopkins Tanne
Journal: BMJ (2006)

Universities should change the way they license research developments so as to make new drugs, vaccines, and diagnostic tests available to people in poor countries, says Universities Allied for Essential Medicines, a coalition of students at universities across North America. 

The group's “Philadelphia consensus” says that universities should promote equal access to the results of their research, conduct research on neglected diseases, and measure their research success by its effect on human welfare. 

“Universities are key developers of drugs, …
Pleuropulmonary fibrosis associated with chronic and excessive intake of ergotamine.
Authors: B G Taal, E L Spierings, C Hilvering
Journal: Thorax (1983)

Retroperitoneal, pleuropulmonary, and endocardial fibroses are relatively uncommon but serious side effects of the prophylactic antimigraine drug methysergide.1 2 Ergotamine is a potent drug in the treatment of the migraine attack, and is chemically related to methysergide.Retroperitoneal fibrosis has been reported in ergotamine users3-' and recently the occurrence of pleuropulmonary fibrosis with ergotamine was described.6In the case reported here a causal relationship between the long-term use of ergotamine and the occurrence of pleuropulmonary fibrosis appears highly probable. Case reportThe patient had started suffering from headaches at the age of 36 years.At first the headaches occurred once a week and lasted for one to two days.They were accom- panied by nausea and vomiting but there was no photo- phobia or phonophobia and no prodromal symptoms.The patient's mother and three sisters also suffered from recur- rent headaches.In 1964, when he was 42, a neurologist diagnosed his headaches as probably migrainous and prescribed Cafergot suppositories, which contain 2 mg ergotamine tartrate and 100 mg caffeine.This had a favourable effect on the attacks.Gradually, however, the frequency of the headaches increased and finally the patient took two or three suppositories a day.The headaches changed in character.Instead of occurring in attacks, the pain became more chronic, although varying in intensity, and was more like a burning sensation at the vertex.The headache was aggravated by the consumption of alcohol and emotional excitement.Several prophylactic drugs, such as clonidine, pizotifen, and a compound tablet containing belladonna alkaloids, phenobarbitone, and ergotamine tartrate, were prescribed without success; but he never used methyser- gide.In June 1975 the patient felt feverish and had a produc- tive cough.Although these symptoms disappeared after three months he gradually became short of breath.He noted that he could no longer take a deep breath because the movement of his chest seemed to be restricted, but he had no chest pain.His appetite decreased and he lost 10 kg
Proapoptotic and antiapoptotic markers in cutaneous T-cell lymphoma skin infiltrates and lymphomatoid papulosis
Authors: H. Nevala, L. Karenko, L. Vakeva, A. Ranki
Journal: British Journal of Dermatology (2001)

Journal Article Proapoptotic and antiapoptotic markers in cutaneous T‐cell lymphoma skin infiltrates and lymphomatoid papulosis Get access H. Nevala, H. Nevala Department of Dermatology and Venereal Diseases, Helsinki University Central Hospital, PO Box 160, 00029 HUS, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar L. Karenko, L. Karenko Department of Dermatology and Venereal Diseases, Helsinki University Central Hospital, PO Box 160, 00029 HUS, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar L. Väkevä, L. Väkevä Department of Dermatology and Venereal Diseases, Helsinki University Central Hospital, PO Box 160, 00029 HUS, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar A. Ranki A. Ranki Department of Dermatology and Venereal Diseases, Helsinki University Central Hospital, PO Box 160, 00029 HUS, Helsinki, Finland Professor Annamari Ranki.E‐mail: Annamari.Ranki@hus.fi Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 145, Issue 6, 1 December 2001, Pages 928–937, https://doi.org/10.1046/j.1365-2133.2001.04523.x Published: 01 December 2001
The TNFRSF1A R92Q mutation is frequent in rheumatoid arthritis but shows no evidence for association or linkage with the disease
Authors: P. Dieude, M. Goossens, F. Cornelis, L. Michou, T. Bardin, D. O. Tchernitchko
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b><i>TNFRSF1A</i> mutations cause <i>TNFRSF1A</i>-associated periodic syndrome (MIM#142680). A recent study suggested that the R92Q mutation was associated with polyarthritis. We aimed to search for this and other <i>TNFRSF1A</i> mutations in rheumatoid arthritis (RA), and to test for linkage. <b>Methods:</b> The DNA of 100 trio families and 86 index cases of RA-affected sib-pair (ASP) families from the French Caucasian population were investigated by denatured high-performance liquid chromatography for <i>TNFRSF1A</i> mutations in exons 2 to 4. The test for association compared cases and controls (derived from un-transmitted parental chromosomes). The test for linkage relied on the transmission disequilibrium test (TDT) in trio families and cosegregation in ASP families. <b>Results:</b> Only the R92Q mutation was detected – in 2 of the 100 index cases of trio families and in 5 (5.8%) of the index cases of ASP families, but also in 5% of the controls, showing no association with the disease. No RA linkage evidence was found in TDT and ASP RA families. <b>Conclusion:</b> This <i>TNFRSF1A</i> investigation in RA from the French Caucasian population showed only the R92Q mutation, with a frequency of 4.5%, but no evidence for RA association or linkage to the disease. The R92Q mutation could be considered to be a low-penetrance variant.
The Chemotherapy of Neoplastic Diseases.
Authors: J. F. Ross
Journal: Annals of Internal Medicine (1961)

s1 May 1961The Chemotherapy of Neoplastic Diseases.J. F. Ross, M.D., F.A.C.P.J. F. Ross, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-54-5-1065_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNever in the history of mankind has an effort to control disease equalled the tremendous attack now being made upon the nature, cause, and cure of cancer. Hundreds of millions of dollars and the efforts of thousands of investigators are being devoted to the study of cancer and to methods of treatment. A major portion of this program is directed to the development of chemotherapeutic methods of control of neoplasia. Vast numbers of substances ranging from crude plant and animal tissue extracts to carefully designed synthetic chemical compounds are being tested for their effectiveness as cancerocidal or cancerostatic agents.What... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Los Angeles, Calif. (ML) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1961Volume 54, Issue 5Page: 1065-1065KeywordsCancer treatmentChemotherapy ePublished: 1 December 2008 Issue Published: 1 May 1961 PDF downloadLoading ...
Concordant Gene Expression Signatures Predict Clinical Outcomes of Cancer Patients Undergoing Systemic Therapy
Authors: Paul D. Williams, Sooyoung Cheon, Dmytro M. Havaleshko, Hyeon Jeong, Feng Cheng, Dan Theodorescu, Jae K. Lee
Journal: Cancer Research (2009)

Conventional development of multivariate gene expression models (GEM) predicting therapeutic response of cancer patients is based on analysis of patients treated with specific regimens, which limits generalization to different or novel drug combinations. We overcome this limitation by developing GEMs based on in vitro drug sensitivities and microarray analyses of the NCI-60 cancer cell line panel. These GEMs were evaluated in blind fashion as predictors of tumor response and/or patient survival in seven independent cohorts of patients with breast (n = 275), bladder (n = 59), and ovarian (n= 143) cancer treated with multiagent chemotherapy, of which 233 patients were from prospectively enrolled clinical trials. In all studies, GEMs effectively stratified tumor response and patient survival independent of established clinical and pathologic tumor variables. In bladder cancer patients treated with neoadjuvant methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin, the 3-year overall survival for those with favorable GEM scores was 81% versus 33% for those with less favorable scores (P = 0.002). GEMs for breast cancer patients treated with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide and ovarian cancer patients treated with platinum-containing regimens also stratified patient survival [5-year overall survival 100% versus 74% (P = 0.05) and 3-year overall survival 68% versus 43% (P = 0.008), respectively]. Importantly, clinical prediction using our in vitro GEM was superior to that of conventionally derived GEMs. We show a facile yet effective approach to GEM derivation that identifies patients most likely to benefit from selected multiagent therapy. Use of such in vitro-based GEMs may provide a robust and generalizable approach to personalized cancer therapy.