tbuckley/cabot-search huggingface dataset:
THE VALUE OF PENICILLIN IN THE CONTROL OF SEPSIS COMPLICATING A CASE OF SEVERE GRANULOCYTOPENIA (ALEUKEMIC LEUKEMIA)
Authors: Victor H. Kugel, Maurice A. Schnitker
Journal: Annals of Internal Medicine (1945)

Case Reports1 December 1945THE VALUE OF PENICILLIN IN THE CONTROL OF SEPSIS COMPLICATING A CASE OF SEVERE GRANULOCYTOPENIA (ALEUKEMIC LEUKEMIA)VICTOR H. KUGEL, MAURICE A. SCHNITKERVICTOR H. KUGELSearch for more papers by this author, MAURICE A. SCHNITKERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-23-6-1001 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe variety of agents used to stimulate the bone marrow in neutropenic states has usually produced indifferent (equivocal) results. This has led several investigators to attempt to modify the course of an agranulocytosis by combating the complicating sepsis. According to Dameshek and Wolfson1"death (in agranulocytosis) is probably the result of overwhelming sepsis in a body stripped of its granulocyte defenses." These authors reasoned that if sepsis could be controlled until such time as spontaneous recovery of function of the bone marrow might take place, a better therapeutic result might occur. They reported two cases of agranulocytosis occurring after aminopyrine...Bibliography1. DAMESHEKWOLFSON WLE: A preliminary report on the treatment of agranulocytosis with sulfathiazole, Am. Jr. Med. Sci., 1942, cciii, 819. CrossrefGoogle Scholar2. NIXONECKERTHOLMES NJFKB: The treatment of agranulocytosis with sulfadiazine, Am. Jr. Med. Sci., 1943, ccvi, 713. CrossrefGoogle Scholar3. HERRELLNICHOLASHEILMAN WEDRDH: Penicillin. Its usefulness, limitations, diffusion and detection, with analysis of 150 cases in which it was employed, Jr. Am. Med. Assoc., 1944, cxxv, 1003. CrossrefGoogle Scholar4. WATKINS CH: The possible rôle of barbiturates and amidopyrine in the causation of leukopenic states, Proc. Staff Meet., Mayo Clin., 1933, viii, 713. Google Scholar5. SPRAGUEFERGUSON HBLK: Agranulocytosis treated with penicillin, U. S. Nav. Med. Bull., 1944, xliii, 1014. Google Scholar6. MEREDITHDOUGLASFINK WCAHH: Penicillin in malignant granulocytopenia, U. S. Nav. Med. Bull., 1944, xliii, 1017. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication March 7, 1945. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFurther observations on the treatment of the anginal syndrome with thiouracilAcute monocytic leukemia 1 December 1945Volume 23, Issue 6Page: 1001-1006KeywordsBone marrowGranulocytesPenicillinSepsis ePublished: 1 December 2008 Issue Published: 1 December 1945 PDF downloadLoading ...
Abstract 9: Role of Hyperkalemia in the Transmural Activation Rate Gradient and Asystole During Long-Duration Ventricular Fibrillation (LDVF) in Isolated Canine Heart
Authors: Tyson G Taylor, Paul W Venable, Junko Shibayama, Alijca E Booth, Nathaniel L Rhodes, Mark Warren, Alexey V Zaitsev
Journal: Circulation (2011)

During LDVF in globally ischemic hearts, a transmurally heterogeneous decrease in VF rate (VFR) occurs culminating in asystole. While hyperkalemia is considered to be a major modulator of excitability during ischemia, the magnitude of extracellular potassium ([K + ] o ) accumulation during LDVF and its role in the transmural VFR gradient and asystole remain unknown. Twelve isolated, blood perfused canine hearts underwent 20 min of global ischemia and VF; and an additional 4 hearts were subjected to VF during normoxic perfusion with varying [K + ] o (2 - 15 mM). Plunge needle electrodes with electrical and K + sensors were used for left ventricular endocardial (ENDO) and epicardial (EPI) measurements of VFR and [K + ] o . Cluster analysis revealed a dichotomy in the timing of asystole (Figure A, Inset): 6/12 hearts experienced asystole at 7.2 ± 1.0 min of ischemia (EARLY ASYS), while the remaining 6/12 hearts were still in VF at 20 min of ischemia (LATE ASYS). EARLY ASYS showed significantly faster K + accumulation in ENDO and EPI than LATE ASYS; neither group developed a gradient in [K + ] o (Figure A). Nevertheless, a prominent ENDO-EPI VFR gradient developed during LDVF in both groups (not shown). Compared to normoxic VF, LDVF exhibited a marked decrease in VFR as a function of [K + ] o . In addition, there was a significant difference in K + sensitivity of VFR between ENDO and EPI which was not observed during normoxic VF (Figure B). We conclude that during LDVF enhanced K + leak predicts early asystole, but the level of [K + ] o per se cannot explain VFR decline either in EPI or ENDO. Thus, hyperkalemia is not the main determinant of electrical depression and asystole during LDVF.
Abstract 1040: Lower-Limb Amputation in Patients With Type 2 Diabetes Mellitus: Factors Predicting Risk in the FIELD Study
Authors: Kushwin Rajamani, Li-Ping Li, Y A Kesaniemi, Merryn Voysey, David Hunt, Paul Drury, Michael C D'Emden, Peter G Colman, Marja-Riitta Taskinen, Anthony C Keech
Journal: Circulation (2009)

Introduction: The major cause of nontraumatic amputation in the developed world is type 2 diabetes. Lower-limb amputations in type 2 diabetes have profound effects on quality of life and pose a maj...
Abstract P4-05-05: A novel TP53-dependent role for TLR4 in driving breast cancer
Authors: Svasti Haricharan, Powel H Brown
Journal: Cancer Research (2015)

Abstract Breast cancer is a leading cause of cancer-related death. Toll-like receptor (TLR)-4 is an important mediator of cytokine secretion that is expressed in breast cancer cells, and is frequently mutated in a subset of breast tumors associated with high mutation load and poor patient survival. We show here that TLR4 plays an important role in driving breast cancer growth in a TP53 context-dependent manner. Using siRNA mediated knockdown, pharmacological inhibition and hyperactivation of TLR4 we demonstrate that TLR4 inhibits growth in breast cancer cells with wildtype TP53 by inducing G0/G1 arrest and decreasing mitotic entry. Conversely, in breast cancer cells with mutant TP53, TLR4 acts as an oncogene and drives cell growth by inducing mitosis. Furthermore, we identify the underlying mechanism for this dual TP53-dependent effect of TLR4 on breast cancer cell growth: differential interferon gamma (IFN-γ) secretion by tumor cells into their microenvironment. Hyperactivated TLR4 signaling in TP53 wildtype breast cancer cells results in increased IFN-γ secretion, identified by an unbiased cytokine array and validated by ELISA, thus inhibiting growth in an autocrine/paracrine fashion. Moreover, secreted IFN-γ is both necessary and sufficient for TLR4-induced growth inhibition in TP53 wildtype breast cancer cells. Finally, the dual TP53-dependent effect of TLR4 extrapolates to several other cancer types in silico, attaching potentially global significance to these results. Taken together, the data presented in this paper strongly suggest a novel role for TLR4 as a suppressor of cell growth in TP53 wildtype tumors, and identify differential IFN-γ secretion as the underlying mechanism. The results of this study are also translationally relevant, delineating the TP53 mutant breast cancer subset as a group that can benefit from pharmacological TLR4 inhibition. Most importantly, these results indicate a need for studying the effect of drivers of cancer growth pleiotropically rather than as isolated events. Citation Format: Svasti Haricharan, Powel H Brown. A novel TP53-dependent role for TLR4 in driving breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-05.
Head-to-Head Comparison of 2 Myocardial Fibrosis Biomarkers for Long-Term Heart Failure Risk Stratification
Authors: Antoni Bayes-Genis, Marta de Antonio, Joan Vila, Judith Peñafiel, Amparo Galán, Jaume Barallat, Elisabet Zamora, Agustin Urrutia, Josep Lupón
Journal: Journal of the American College of Cardiology (2013)
Abstract 674: Coupling Factor 6 Activates c-Src By Intracellular Acidosis And Enhances Calcium Signaling In Resistance Arteriole Smooth Muscle Cells
Authors: Tomohiro Osanai, Makoto Tanaka, Hirofumi Tomita, Masahiro Yamada, Sin Saitoh, Akiko Kumagai, Reiichi Murakami, Toshihiro Ashitate, Takashi Echizen, Chisato Katoh, Hiroaki Yokoyama, Ken Okumura
Journal: Circulation (2007)

In vascular endothelial cells, coupling factor 6 (CF6) binds to the β subunit of plasma membrane ATP synthase and attenuates prostacyclin generation by inducing intracellular acidosis. However, intracellular signaling in resistance arterioles that is directly related to vascular tonus and hypertension has not been determined yet. We investigated the direct effect of CF6 on Ca 2+ signaling, involvement of c-Src in it, and the role of CF6 in the pathogenesis of hypertension. CF6 at 10 −7 M induced a monophasic increase in intracellular free Ca 2+ concentration ([Ca 2+ ] i ) in A7r5 cells (rat vascular smooth muscle cells (VSMC) expressing voltage-gated Ca 2+ channel). When CF6 at 10 −7 M was added after pretreatment with nifedipine at 10 −5 M, the sustained increase in [Ca 2+ ] i was abolished. In cultured resistance arteriole VSMC obtained from the mesenteric artery network of spontaneously hypertensive rats (SHR, n = 8) and Wistar Kyoto rats (WKY, n = 8), angiotensin II (Ang II) at 10 −7 M caused a spike increase in [Ca 2+ ] i followed by a sustained increase. When Ang II at 10 −7 M was added after pre-administration of CF6 at 10 −7 M, the spike phase of [Ca 2+ ] i was enhanced and it was greater in SHR than in WKY (412 ± 26 vs 162 ± 14 nM, p &lt; 0.05). Pretreatment with PP1 at 50 μM, a c-Src inhibitor, blocked not only the CF6-induced Ca 2+ influx but the CF6-induced increase in the AngII-mediated spike phase of [Ca 2+ ] i . CF6 receptor of VSMC was the β-subunit of ATP synthase, and the affinity was higher in SHR than in WKY (Kd: 3.6 ± 0.3 vs 9.6 ± 0.3 nM, p &lt; 0.05). The increase in ATPase activity by CF6 was greater in SHR than in WKY (p &lt; 0.05), and the decrease in intracellular pH was greater in SHR than in WKY (0.26 ± 0.03 vs 0.13 ± 0.02, p &lt; 0.05). CF6 activated c-Src at 15 minutes by 2 folds greater in SHR than in WKY, and it was blocked by efrapeptine at 10 −5 M, an ATPase inhibitor. In mesenteric arterioles obtained from CF6-transgenic mice (2 fold over-expressed), AngII caused greater vasoconstriction by 2 folds than in those from wild mice (p &lt; 0.05), but it was abolished by pretreatment with PP1. These suggest that CF6 activates c-Src by inducing intracellular acidosis and enhances Ca 2+ signaling in resistance arteriole VSMC. Since the c-Src activation was enhanced in SHR, CF6 might be involved in the genesis of hypertension.
n of1 trials in osteoarthritis
Authors: C J Hawkey
Journal: BMJ (1995)

Data collection should be integrated with patient care EDITOR,-The editorial on making routine data adequate to support clinical audit mentions the high quality of data from the St Mary's maternity information system,' citing two recent papers on its validity.23The editorial's authors, however, have missed the point about why this particular system has proved so successful.The basis of the system is that midwives enter the data themselves and then in turn use the system for practical purposes directly associated with patients' care- for example, it generates summaries and discharge letters.The system is thus integrally associated with patients' care and is not a separate task.This experience strongly suggests that abandon- ing the normal practice of relegating the input of data to clerical staff results in better quality of data.This is both because the motivation of health care professionals is higher and, crucially, because of the reinforcing feedback loop involving the use of the information for patients' care.The Department of Health has introduced an information management and technology strategy for the NHS in England, which has many positive features.4Its potential Achilles' heel, however, is precisely this question of the quality of the data.Although it includes a data quality initiative, this is concerned mainly with administrative data (the postcode and codes for the provider, health authority, and general practitioner), the only clinical element being the code for the diagnosis.5We suggest that a great deal could be learnt from the strengths and weaknesses of existing systems, especially successful ones like St Mary's maternity information system, and could then be used in the development of the future information technology for health care.
Triptolide enhances radiation therapy and reduces radiation-induced toxicity
Authors: Shanmin Yang, Ying Su, Zhenyu Xiao, Wei Wang, Hengshan Zhang, Scott Paoni, Bruce Fenton, Paul Okunieff, Lurong Zhang
Journal: Cancer Research (2006)

4403   Enhancement of therapeutic effect of ionizing radiation (IR) and reduction of IR-induced toxicity is one of major research tasks in cancer radiation therapy. In this study, we explored TPL effect on enhancing IR treatment while reducing IR toxicity with two types of animal models. First, 4T1 breast cancer xenografts grown in the right hind leg of BALB/c mice were treated with TPL (0.2 mg/Kg i.v., three times a week) or IR (10 Gy once) or in combination. Tumor growth delay and tumor weight were measured and compared among the different treatment groups. The inhibitory effect of TPL on angiogenesis was assessed with DiOC7 staining/ vessel spacing in 4T1 tumor xenografts and with CAM (chorioallantoic membranes) of 6 day-old chicken embryos. The results showed that the combination of TPL and IR achieved the greatest tumor response compared to other treatment groups with an Enhancement Factor of 2.1 (measured at 200 mm 3  tumor volume) and a significant reduction of tumor weight. TPL inhibited angiogenesis, evidenced by an increase of vessel spacing in tumors and a decreased vessel number and area in the CAM assay. Second, the right hind legs of mice were irradiated with 30 Gy once. The mice were treated with vehicle alone or TPL (0.25 mg/kg i,v, twice a week) or Celebrex (50 mg/kg/daily) for 4 weeks. The skin score was measured for the extent of IR-induced early dermatitis 2–3 weeks after IR, and the degree of late IR-fibrosis was determined by measurement of leg contraction. The results demonstrated that TPL reduced the extent of dermatitis evidenced by a low skin score. TPL also prevented the late fibrosis evidenced by a less contracted leg as compared to vehicle alone or Celebrex group (9.07% vs. 39.34% or 42.55% of leg shortening).  In vitro , TPL inhibited the proliferation of 4T1 breast cancer cells, LY-2 cells and Raw 264.7 macrophages as measured by sulforhodamine B method, which was related with induction of apoptosis by TPL. In addition, TPL inhibited the IR-induced IL-1α in LY-2 cells. Similarly, TPL suppressed the production of IL-1α, IL-1β, TNF-α TGF-β and IL-6 in irradiated Raw 264.7 cells in a dose-dependent manner. Likewise, mRNA of TGF-β and IL-1α protein in the IR-skin were inhibited by TPL. Using COX inhibitor screen kit, we found that the activities of both COX1 and COX2 were inhibited by TPL (100 ng/ml) with inhibition rate of (32.6±1.8%) and (47.3±1.29%), respectively. It seems that the dual effect of TPL is related with its induction of apoptosis, reduction of cytokines, inhibition of COX and suppression of angiogenesis.
Iodine-131 Ablation Therapy for a Patient Receiving Peritoneal Dialysis
Authors: MARIE-ELISABETH TOUBERT, CATHERINE MICHEL, FABIEN METIVIER, M. CAN PEKER, JEAN-DIDIER RAIN
Journal: Clinical Nuclear Medicine (2001)

The authors describe a patient with follicular thyroid carcinoma who was receiving continuous ambulatory peritoneal dialysis to manage end-stage renal disease. To deliver radioiodine therapy to ablate thyroid remnants safely and under optimal conditions, the behavior of 37 MBq (1 mCi) I-131 was followed daily for 3 days. Blood activity and total body count decreased with a half-life of 100 hours (4.17 days). The daily iodide removal rate, estimated as a percentage of the total administrated activity, was low: 5.3% to 8.6% in peritoneal dialysate and 1.3% to 2.2% in urine. The thyroid uptake, measured using a probe, was 2.4% to 2.1% from day 1 to day 3 and 1.9% later at day 8. The volume of thyroid remnants was determined by ultrasonography to be 0.6 g. The patient received a reduced ablative I-131 dose of 814 MBq (22 mCi). Radiation emitted from the patient after I-131 therapy, monitored using a radiation monitor probe located at a distance of 1 meter, decreased with an effective half-life of 70 hours (2.9 days). The integration of the curve from t = 0 showed a level always less than 25 μSv/hour as early as 24 hours after treatment. Because the iodine removal rate is continuous but low in a case of peritoneal dialysis, smaller therapeutic doses must be administered to deliver maximal radiation to residual thyroid tissue while minimizing excessive radiation exposure to patients, their families, and medical staff.
Abstract 264: Group X Secretory Phospholipase A2 has a Critical Role in Neutrophils Activation and Myocardial Ischemia-reperfusion Injury in Mice
Authors: Daisuke Fujioka, Ken-ichi Kawabata, Yoshikazu Ishimoto, Noriko Suzuki, Kohji Hanasaki, Ryota Sato, Toshiaki Yano, Tsuyoshi Kobayashi, Yukio Saito, Masaki Kanazawa, Kiyotaka Kugiyama
Journal: Circulation (2007)

Secretory phospholipase A2 (sPLA2) plays a critical role in the pathophysiology of cardiovascular diseases. Among several types of sPLA2, group X sPLA2 (sPLA2-X) has the most potent hydrolyzing act...
GUMMATOUS AORTIC VALVULITIS: REPORT OF CASE
Authors: S. H. Auerbach
Journal: Annals of Internal Medicine (1945)

Case Reports1 June 1945GUMMATOUS AORTIC VALVULITIS: REPORT OF CASES. H. AUERBACH, M.D.S. H. AUERBACH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-22-6-870 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptChronic aortitis is the most common tertiary lesion of acquired syphilis and deformity of the valve with incompetence is a customary sequel. The characteristic aortic lesion is essentially an endarteritis,1 followed by necrosis and sclerosis of the media. The adjacent vascularized portions of the valve cusps are affected in the same manner.2 The destructive process rarely approaches the formation of gummas other than microscopic. Thus, Gordon, Parker and Weiss3 were able to collect only seven adequately described cases of frank gummatous aortitis in the literature to 1942 in a report of three additional cases.Gummatous destruction of the aortic valve...Bibliography1. SAPHIRSCOTT ORW: The involvement of the aortic valve in syphilitic aortitis, Am. Jr. Path., 1927, iii, 527-536. Google Scholar2. SAPHIRSTASNEY OJ: Extreme alteration of the aortic valve in syphilitic aortitis, Am. Jr. Path., 1933, ix, 431-442. Google Scholar3. GORDONPARKERWEISS WHFS: Gummatous aortitis, Arch. Int. Med., 1942, lxx, 396-415. CrossrefGoogle Scholar4. SOHVAL AR: Gumma of heart, Arch. Path., 1935, xx, 429-444. Google Scholar5. RICHTER AB: Treponema pallidum in syphilitic aortic valvulitis in congenitally bicuspid valve with subaortic stenosis, Am. Jr. Path., 1936, xii, 129-139. Google Scholar6. GROSSKUGEL LMA: Topographic anatomy and histology of the valves of the human heart, Am. Jr. Path., 1931, vii, 445-474. Google Scholar7. DIETERLE RR: Method for demonstration of Spirochaeta pallida in single microscopic sections, Arch. Neurol. and Psychiat., 1927, xviii, 73-80. CrossrefGoogle Scholar8. NORRIS JC: Myocardial syphilis with aneurysm of the sinus of Valsalva, U. S. Nav. Med. Bull., 1932, xxx, 37-40. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Augusta, Georgia*Received for publication December 28, 1943.From the Department of Pathology, School of Medicine, University of Georgia, Augusta, Georgia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1945Volume 22, Issue 6Page: 870-876KeywordsAortic valveLesionsNecrosisSyphilis ePublished: 1 December 2008 Issue Published: 1 June 1945 PDF downloadLoading ...
Abstract 67: Direct Mail Improves Knowledge of CPR Guidelines 2010 in Primary Care: A Randomized Study
Authors: Bo Løfgren, Niels Secher, Mette Marie Mikkelsen, Kasper Adelborg, Jens Mørch Rubak, Peter Vedsted
Journal: Circulation (2011)

Background: Resuscitation councils publish new guidelines on resuscitation every 5 years. Often there is a significant delay on implementing new guidelines into clinical practice. Direct-mail is an inexpensive way of disseminating information to primary care physicians (PCP) and may improve implementation of new CPR guidelines 2010. Accordingly, the aim of this study was to investigate whether direct-mail improved knowledge on new CPR guidelines among PCPs. Methods: All primary care clinics in Central Region Denmark were randomized to receive either direct-mail (intervention) or no direct-mail (control). The direct-mail consisted of a cover letter outlining changes in CPR guidelines and a poster on CPR and the use of an automatic external defibrillator (AED). In clinics randomized to the intervention every single PCP received a personal direct-mail. Two weeks later a multiple-choice questionnaire on CPR guidelines together with items on characteristics of the PCP were mailed to PCPs in all clinics. Non-responders received a reminder with an additional questionnaire after 20 days. Results: A total of 830 (direct-mail, n=408; control, n=422) PCPs from 351 primary care clinics were included in the study. Overall response rate was 58%. Demographic characteristics were comparable in the two groups. The majority (91%) of PCPs receiving direct-mail stated they were familiar with the new CPR Guidelines 2010 compared to 72% in the control group (P&lt;0.0001). Direct-mail improved the knowledge of the new recommended chest compression depth (67% vs. 40%, P&lt;0.0001) and the new recommended chest compressions frequency (62% vs. 40%, P&lt;0.0001). Conclusion: Direct-mail improves disseminating knowledge on changes in CPR guidelines and thus helps implement new guidelines in general practice. Organizations i.e. resuscitation councils and medical societies for primary care may consider using this inexpensive strategy for implementing changes in clinical guidelines in the future.