tbuckley/cabot-search huggingface dataset:
Even clinician led management won't fix the NHS
Authors: Adam R Greenbaum
Journal: BMJ (2006)

Physical activity to prevent obesity in young children Negative outcome or protocol problem?Editor-Although the article by Reilly et al on physical activity to prevent obesity in young children emphasises that adherence to protocol was good, 1 an interview with Reilly on the Today programme (7.20 am, 6 October 2006) cited the difficulty in getting children to increase their activity as much as required-that is, not a negative outcome, but a problem in achieving sufficient increase to make the intervention effective.Which was the case?
Points from Letters: Role of the Married Nurse
Authors: P. H. Kidner
Journal: BMJ (1967)

MEDICAsOHRNALIn it you will observe that during a 12- month period in 1962/63, in the County Borough of Wolverhampton, a carefully designed prospective survey of random early discharge from hospital of 1,044 mothers and 1,044 babies, each of whom was followed up objectively for two months after confinement, made these important findings: that mortality was non-existent in mothers and small in babies; that morbidity was low for both; that neither could be attributed to early discharge; and that race, not duration of stay, was the most decisive and highly significant factor in establishment and maintenance of breast feeding.It should be added that the final survey confirmed the results of a pilot survey-to test methodology and recording-of 969 simultaneous mother and baby discharges over the preceding twelve months and that it assisted substantially in presentation earlier this year of a case for the revision of the bed ratio on which planning of hospital maternity resources is based.'-I am, etc.,
A Molecular Imaging System Based on Both Transcriptional and Genomic Amplification to Detect Prostate Cancer Cells In Vivo
Authors: Frédéric Pouliot, Makoto Sato, Ziyue Karen Jiang, Steve Huyn, Breanne DW Karanikolas, Lily Wu
Journal: Molecular Therapy (2012)

An imaging modality that can accurately discern prostate cancer (PCa) foci would be useful to detect PCa early or guide treatment. We have engineered numerous adenoviral vectors (Ads) to carry out reporter gene-based imaging using specific promoters to express a potent transcriptional activator, which in turn activates the reporter gene in PCa. This two-step transcriptional amplification (TSTA) method can boost promoters' activity, while maintaining cell specificity. Here, we examined a dual TSTA (DTSTA) approach, which utilizes TSTA not only to express the imaging reporter, but also to direct viral genome replication of a conditionally replicating Ad (CRAd) to further augment the expression levels of the reporter gene by genomic amplification supported in trans by coadministered CRAd. In vitro studies showed up to 50-fold increase of the reporter genome by DTSTA. Compared with TSTA reporter alone, DTSTA application exhibited a 25-fold increase in imaging signal in PCa xenografts. DTSTA approach is also beneficial for a combination of two TSTA Ads with distinct promoters, although amplification is observed only when TSTA-CRAd can replicate. Consequently, the DTSTA approach is a hybrid method of transcriptional and genomic augmentation that can provide higher level reporter gene expression potentially with a lower dose of viral administration.
Carbohydrate of the Factor VIII/von Willebrand Factor in von Willebrand's Disease
Authors: T. S. Zimmerman, R. Voss, T. S. Edgington
Journal: Journal of Clinical Investigation (1979)

We have examined the plasma Factor VIII/von Willebrand factor (FVIII/vWF) molecule from 16 patients with von Willebrand's disease, and have found no evidence of a significant decrease of carbohydrate content in 15 of these patients. FVIII/vWF was isolated by preparative counter immunoelectrophoresis directly from plasma using antibody to Factor VIII-related antigen, reduced in sodium dodecyl sulfate in the presence of urea, and electrophoresed in 5% polyacrylamide gels to separate the FVIII/vWF subunit from other proteins. Duplicate gels were stained by either the periodic acid-Schiff (PAS) reaction or by Coomassie Brilliant Blue G250. The ratio of Coomassie: PAS was determined by spectrophotometric scanning of the gels. Transferrin was used as an internal reference standard. The ratio for 23 normal individuals was 2.4±0.38 and the observed range was 1.8-3.8. 15 patients with von Willebrand's disease fell within this range. One patient independently reported as having decreased FVIII/vWF carbohydrate was also studied by this technique. A ratio of 6.8 was found, indicative of decreased, though not absent, carbohydrate. Cold insoluble globulin did not represent a significant contaminant in these analyses. 11 of the von Willebrand's disease patients with normal FVIII/vWF carbohydrate had abnormal crossed immunoelectrophoretic patterns characterized by absence of the less anodic forms of Factor VIII-related antigen. Four patients had normal patterns. These studies indicate that an absence or decrease of PAS reactive FVIII/vWF carbohydrate is not a consistent abnormality in von Willebrand's disease.
Incidence of Thyroid Disorders in Connecticut
Authors: David B. Baldwin
Journal: JAMA (1978)

A prospective study involving 1,544 patients who had annual physical examinations during a one-year period was conducted to determine the incidence of htyroid abnormalities in a practice of general internal medicine. A total of 5.8% abnormalities were found including nodular disease, thyroiditis, Graves' disease, hypothyroidism, simple goiter, and iatrogenic hyperthyroidism. No thyroid cancer was detected.
The Politics of Philanthropy: Abraham Flexner and Medical Education
Authors: Martin Kaufman
Journal: JAMA (1989)

In this book Steven C. Wheatley, director of the American studies program for the American Council of Learned Societies, examines the career of Abraham Flexner, a leader in the movement to reform medical education during the Progressive era. There is no doubt about the significant role of Flexner, whose 1910 report on medical education in the United States and Canada helped to crystallize reform sentiment, and who until 1928 worked for the Rockefeller philanthropies as principal officer overseeing grants for medical education. Just as is the case with science, one historical researcher builds upon the works of his or her predecessors; if the researcher asks "new" questions, uses "new" sources, or utilizes statistical techniques or methods of other social sciences, the resulting study can substantially add to our understanding of historical developments. In order to place Wheatley's book in perspective, it is useful to briefly describe the recent historiography of
<i>In Vivo</i> Regulation of TGF-β by R-Ras2 Revealed through Loss of the RasGAP Protein NF1
Authors: Deanna M. Patmore, Sara Welch, Patricia C. Fulkerson, Jianqiang Wu, Kwangmin Choi, David Eaves, Jennifer J. Kordich, Margaret H. Collins, Timothy P. Cripe, Nancy Ratner
Journal: Cancer Research (2012)

Abstract Ras superfamily proteins participate in TGF-β—mediated developmental pathways that promote either tumor suppression or progression. However, the specific Ras proteins, which integrate in vivo with TGF-β signaling pathways, are unknown. As a general approach to this question, we activated all Ras proteins in vivo by genetic deletion of the RasGAP protein Nf1 and examined mice doubly deficient in a Ras protein to determine its requirement in formation of TGF-β—dependent neurofibromas that arise in Nf1-deficient mice. Animals lacking Nf1 and the Ras-related protein R-Ras2/TC21 displayed a delay in formation of neurofibromas but an acceleration in formation of brain tumors and sarcomas. Loss of R-Ras2 was associated with elevated expression of TGF-β in Nf1-deficient Schwann cell precursors, blockade of a Nf1/TGFβRII/AKT-dependent autocrine survival loop in tumor precursor cells, and decreased precursor cell numbers. Furthermore, the increase in size of sarcomas from xenografts doubly deficient in these genes was also found to be TGF-β—dependent, in this case resulting from cell nonautonomous effects on endothelial cells and myofibroblasts. Extending these findings in clinical specimens, we documented an increase in TGF-β ligands and an absence of TGF-β receptor II in malignant peripheral nerve sheath tumors, which correspond to tumors in the Nf1-deficient mouse model. Together, our findings reveal R-Ras2 as a critical regulator of TGF-β signaling in vivo. Cancer Res; 72(20); 5317–27. ©2012 AACR.
ABC of antenatal care. Vital statistics of birth.
Authors: G Chamberlain
Journal: BMJ (1991)

Doctors are mostly literate but are commonly innumerate.We are largely ignorant and frightened of the safe and helpful use of figures because we have never been taught to understand them properly.In consequence we often try to dismiss them, believing that they are used during medical debate in a biased fashion to support the arguments of the proponents but are put to one side as non-relevant or non-significant by the opponents.This is a head in the sand attitude as statistics are extremely helpful in providing evidence of changes.Obstetricians are in fact well used to monitoring their activities statistically, having collected and published data long before the current fashion for audit started.To be useful medical statistics must be * Collected properly from a prescribed population * Analysed in a valid fashion so as not to produce bias * Presented promptly in a digestible, unbiased form.In the United Kingdom these three criteria have been met by the national statutory handling of data on births, perinatal deaths, and maternal deaths.District registrars refer data centrally to the registrars general of the four kingdoms; checking, analysis, and comment on final data comes from the Office of Population, Censuses and Surveys in London and from equivalent departments in Wales, Scotland, and Northern Ireland.The Scottish system currently gives the most speedy and best produced information. Birth ratesThe number of babies born is counted by two processes, birth registration and birth notification.These are two statutory obligationsregistration on parents, notification on professional staff.Birth rates are often expressed as a ratio of the number of births to the number of people in the existing population, usually gathered from the decennial census. Birth rate =No of births x 1000 No of people in the population The birth rate in the United Kingdom in 1988 was 7-3 per 1000.The denominator in the birth rate formula includes, however, men, who never give birth, and women under 15 and over 44, who are mostly outside the reproductive age group.Hence the denominator does not relate to the numerator very well; an alternative measure is more commonly used in the Western world.
Acute Myeloblastic Leukemia and Hypercalcemia
Authors: Bernard L. Zidar, Richard K. Shadduck, Alan Winkelstein, Zella Zeigler, Charles D. Hawker
Journal: New England Journal of Medicine (1976)

We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukemia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freezethawing experiments, 39 pg of parathyroid hormone was released from 1 X 108 of the patient's myeloblasts; no hormone was released from the normocalcemic cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells. (N Engl J Med 295:692–694, 1976)
Treatment of Enterobiasis
Authors: R. H. R. White
Journal: BMJ (1963)

Treatment of EnterobiasisSIR,-In introducing his report on the treatment of enterobiasis with a single dose of pyrvinium embonate (December 15, p. 1583), Dr. A. S. Desai states that " the piperazine group . . .has to be administered over a period of 7 to 15 days in three daily divided doses to achieve good results."He is evidently unaware of the results achieved by Dr. J. W. Scopes and myself' with a single dose of piperazine phosphate compounded with standardized senna (" pripsen ").Both preparations appear to be equally effective and free from side-effects; but pyrvinium embonate apparently suffers from the very considerable disadvantage, mentioned but not discussed by Dr. Desai, that it is ineffective against Ascaris lumbricoides, a parasite of immensely greater clinical importance amongst children in his own country and in warm climates throughout the world.-I am, etc.,
Benefit of Thrombolytic Therapy Is Sustained Throughout Five Years and Is Related to TIMI Perfusion Grade 3 But Not Grade 2 Flow at Discharge
Authors: Timo Lenderink, Maarten L. Simoons, Gerrit-Anne Van Es, Frans Van de Werf, Marc Verstraete, Alf E.R. Arnold
Journal: Circulation (1995)

Background Long-term follow-up in patients treated with thrombolysis for acute myocardial infarction thus far has been reported in a few studies only, and no long-term follow-up is available for patients who underwent additional percutaneous transluminal coronary angioplasty (PTCA). This report describes 5-year survival as collected in patients who received placebo, recombinant tissue plasminogen activator (rTPA), or rTPA with additional immediate PTCA in two European Cooperative Study Group trials. Determinants for long-term survival were assessed in 1043 patients discharged alive. Methods and Results Five-year follow-up information on mortality was collected. Hospital mortality was lower after rTPA than placebo (2.5% versus 5.7%, P =.04) and higher after rTPA with immediate PTCA compared with rTPA without additional intervention (6.0% versus 2.2%, P =.07). Of the 1043 hospital survivors, data were available for 923 patients, of whom 109 died. In the placebo group, mortality after hospital discharge was 10.7% versus 11.0% in the comparative rTPA group. The patients treated with rTPA and immediate PTCA had a mortality rate of 10.5% versus 8.9% in the rTPA group without PTCA (all P =NS). Significant determinants of mortality in multivariate proportional hazards analysis were enzymatic infarct size, indicators of residual left ventricular function, number of diseased vessels and TIMI perfusion grade at discharge. Patients with TIMI grade 2 flow had mortality rates similar to those with TIMI flow grades 0 and 1, while prognosis was better in patients with TIMI flow grade 3. Conclusions The initial in-hospital benefit of thrombolysis with intravenous rTPA is maintained throughout 5 years, with no early or late beneficial effect of systematic immediate PTCA. Enzymatic infarct size, left ventricular function, and extent of coronary artery disease are predictors for long-term survival. TIMI perfusion grade 2 at discharge should be considered as an inadequate result of therapy.
Choice of Antibody Immunotherapy Influences Cytomegalovirus Viremia in Simultaneous Pancreas-Kidney Transplant Recipients
Authors: Volkert A.L. Huurman, Jayant S. Kalpoe, Pieter van de Linde, Norbert Vaessen, Jan Ringers, Aloys C.M. Kroes, Bart O. Roep, Johan W. De Fijter
Journal: Diabetes Care (2006)

OBJECTIVE—Simultaneous pancreas-kidney (SPK) transplantation in type 1 diabetic patients requires immunotherapy against allo- and autoreactive T-cells. Cytomegalovirus (CMV) infection is a major cause for morbidity after transplantation and is possibly related to recurrent autoimmunity. In this study, we assessed the pattern of CMV viremia in SPK transplant recipients receiving either antithymocyte globulin (ATG) or anti-CD25 (daclizumab) immunosuppressive induction therapy. RESEARCH DESIGN AND METHODS—We evaluated 36 SPK transplant recipients from a randomized cohort that received either ATG or daclizumab as induction therapy. Patients at risk for CMV infection received oral prophylactic ganciclovir therapy. The CMV DNA level in plasma was measured for at least 180 days using a quantitative real-time PCR. Recipient peripheral blood mononuclear cells were cross-sectionally HLA tetramer-stained for CMV-specific CD8+ T-cells. RESULTS—Positive CMV serostatus in donors was correlated with a higher incidence of CMV viremia than negative serostatus. In patients at risk, daclizumab induction therapy significantly prolonged CMV-free survival. CMV viremia occurred earlier and was more severe in patients with rejection episodes than in patients without rejection episodes. CMV-specific CD8+ T-cell counts were significantly lower in patients developing CMV viremia than in those who did not. CONCLUSIONS—Despite their comparable immunosuppressive potential, daclizumab is safer than ATG regarding CMV infection risk in SPK transplantation. ATG-treated rejection episodes are associated with earlier and more severe infection. Furthermore, high CMV-specific tetramer counts reflect antiviral immunity rather than concurrent viremia because they imply low viremic activity. These findings may prove valuable in the discussion on both safety of induction therapy and recurrent autoimmunity in SPK and islet transplantation.
Survey of the Law of Medical Practice
Authors: Sidney Shindell
Journal: JAMA (1965)

All of the previous communications in this series L have dealt with rules of law. Society establishes a norm of conduct and provides for redress if there has been deviation from that norm. When we dealt with the essential nature of the physicianpatient relationship as a contract we indicated that one of the established norms of society is that a physician will be bound by any specific promise he makes as to form of therapy to be used or results to be obtained. This norm has been formalized and has status as a rule of law. Should a patient claim that he has been damaged because a physician did not adhere to the terms of a specific agreement, he is requesting that society accord him the redress afforded by our legal system. Before society will do so, however, it must be assured that the claimed set of circumstances in fact
ME-10 * TUMOR MICROENVIRONMENT INFILTRATING MYELOID DERIVED SUPPRESSOR CELLS INHIBIT ANTI-TUMOR T CELL RESPONSES
Authors: N. Kamran, M. Ayala, Y. Li, H. Assi, M. Candolfi, M. Dzaman, P. Lowenstein, M. Castro
Journal: Neuro-Oncology (2014)

MDSCs represent a population of immature myeloid cells at various stages of differentiation that inhibit anti-tumor T cell-mediated responses. We demonstrate the accumulation of MDSCs in GL26 induced glioma and B16 melanoma bearing mice. Absolute numbers of Ly-6G+ (Gr-1high) MDSCs showed a 200 fold increase within the tumor microenvironment (TME) 28 days post-tumor implantation. The numbers of Ly-6C+ (Gr-1low) MDSCs also showed a similar trend within the TME. While this massive influx of MDSCs was noted within intracranial tumors, MDSC levels did not increase in the dLNs, spleen or bone marrow (BM) of intracranial tumor bearing mice. MDSCs numbers were significantly elevated in the blood of GL26 intracranial tumor bearing mice at 28 days. Mice bearing B16 tumors in the flank showed a ∼5 fold increased influx of Ly-6G+ MDSCs while the Ly6C+ MDSCs increased marginally by 1.1 fold within the tumor mass. Levels of circulating MDSCs also increased by ∼10 fold, while the levels of splenic MDSCs did not change. While both Ly-6G+ and Ly6C+ MDSCs isolated from the brain TME of GL26 intracranial tumor bearing mice inhibited antigen-specific T cell proliferation, Ly6C+ MDSC were found to be more efficient. Ly6G+ or Ly6C+ MDSCs from the bone marrow of intracranial tumor bearing mice failed to suppress antigen-specific T cell proliferation. Splenic and bone marrow MDSCs from naïve mice also did not inhibit antigen-specific T cell proliferation suggesting that TME derived factors may activate MDSCs to exert their immune-suppressive properties. Microarray analysis of glioma cell lines showed elevated levels of CXCL1 mRNA and splenic MDSCs from GL26 tumor mice showed upregulation of the CXCR2 mRNA. Preliminary experiments indicate that CXCR2 signaling mediates MDSC chemotaxis. Overall, our data suggests that strategies that inhibit MDSC recruitment to the TME and/or block their activity could enhance the T cell mediated tumor clearance.
Degeneration of the Cardiac Nerves in Chagas' Disease
Authors: J. C. MANÇO, L. GALLO, R. A. GODOY, R. G. FERNANDES, D. S. AMORIM
Journal: Circulation (1969)

The Valsalva maneuver was performed by a series of eight patients with chronic Chagas' heart disease who had no current evidence nor past history of heart failure. The fact that all the patients showed recovery of arterial pressure during the latter portion of the period of increased airway pressure and exhibited significant overshoot in pressure in the post-straining period of the Valsalva maneuver strongly suggests that reflex activity of arteriolar tone was present. However, slowing of the heart rate was not found in association with the blood pressure overshoot in half of the patients. This abnormal response was observed only in patients in whom atropine sulfate failed to cause an increase in heart rate. These results are interpreted as a further indication of degeneration of autonomic nervous system controlling heart rate in chronic Chagas' heart disease.
A8.8 Controllable hydrogen sulfide donors and their anti-inflammatory potential in the murine macrophage cell line RAW264.7
Authors: Burkhard Kloesch, Tatjana Becker, Yu Zhao, Ming Xian, Guenter Steiner
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Hydrogen sulfide (H<sub>2</sub>S) is a newly discovered gaseous signalling molecule like CO and NO and plays an important role in many physiological and/or pathological processes. Modulation of H<sub>2</sub>S levels could have tremendous therapeutic value. However, the research on H<sub>2</sub>S has been hindered by lacking controllable H<sub>2</sub>S donors which could mimic the slow and continuous H<sub>2</sub>S generation in vivo. In this study we report about the biological evaluation of a new class of H<sub>2</sub>S donors releasing H<sub>2</sub>S upon activation by cysteine or reduced glutathione (GSH). <h3>Material and Methods</h3> The murine macrophage cell line RAW264.7 was preincubated for 1 hr with increasing concentrations (10 – 500 µM) of the H<sub>2</sub>S donors termed 5a, 5b, 8a and 8l in the presence of 1 mM cysteine before the cells were stimulated for 24 hrs with LPS (100 ng/ml). Vice versa, macrophages were stimulated for 6 hrs with LPS and cells were post-treated with the compounds at the same concentrations plus cysteine. TNF-α and IL-6 levels were quantified by ELISAs. Nitrite as a marker for iNOS activation was monitored by a commercially available kit. Activation of the transcription factor NF-κB and modulation of mitogen activated protein kinases (MAPKs) such as p38 and ERK1/2 were analysed by Western blot. <h3>Results</h3> The compounds 5a and 8a showed potent anti-inflammatory effects in RAW267.4 cells. TNF-α and IL-6 expression was effectively diminished even when the cells were post-treated with the compounds after LPS stimulation. In line with these results, nitrite production was also reduced demonstrating that these compounds also blocked activation of iNOS. In contrast to the compounds 5a and 8a, the inhibitory effects of 5b and 8l on TNF-α and IL-6 expression were much less pronounced. <h3>Conclusions</h3> This study gives a first insight into the cellular mechanism of these new class of inducible H<sub>2</sub>S-releasing compounds and suggest it as possible remedies for the treatment of chronic inflammatory diseases like RA.