tbuckley/cabot-search huggingface dataset:
L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.
Authors: M A Creager, S J Gallagher, X J Girerd, S M Coleman, V J Dzau, J P Cooke
Journal: Journal of Clinical Investigation (1992)

Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.
Prediction of ReversibleIschemia After Revascularization
Authors: Nagara Tamaki, Masahide Kawamoto, Eiji Tadamura, Yasuhiro Magata, Yoshiharu Yonekura, Ryuji Nohara, Shigetake Sasayama, Kazunobu Nishimura, Toshihiko Ban, Junji Konishi
Journal: Circulation (1995)

Background Accurate noninvasive determination of myocardial viability is of paramount importance for the clinical identification of patients who will benefit most from revascularization. The preserved metabolic activity in the myocardium, as studied with positron emission tomography (PET), has been considered a gold standard for this purpose. However, recent reports show that moderate hypoperfusion or stress-induced ischemia may represent reversible ischemia. The present study was undertaken to compare the value of perfusion and metabolic studies with PET for predicting improvement in wall motion after revascularization. Methods and Results Of 61 patients who had regional asynergy and underwent PET before revascularization, 43 patients who had successful revascularization were included in the study. Each patient underwent rest-stress 13 N-ammonia perfusion scans and 18 F-fluorodeoxyglucose (FDG) scan at rest while in a fasting state. Reversible ischemia was considered to be present when the resting perfusion was ≥50% of the peak value, stress-induced hypoperfusion was present, or an increase in FDG uptake was observed. Of 130 asynergy segments, 51 segments had improved wall motion after revascularization. The positive and negative predictive values for improvement in asynergy were 48% and 87% by the rest perfusion study, 63% ( P =.05 versus the rest value) and 87% by the rest-stress perfusion study, and 76% ( P &lt;.01 versus the rest value) and 92% by the FDG study. Conclusions FDG PET provided the best predictive value for improvement in wall motion after revascularization. On the other hand, 13 N-ammonia PET is useful for predicting nonreversible myocardial scarring when it shows severe hypoperfusion at rest or hypoperfusion without stress-induced ischemia.
Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults
Authors: Santosh Kesari, David Schiff, John W. Henson, Alona Muzikansky, Debra C. Gigas, Lisa Doherty, Tracy T. Batchelor, Janina A. Longtine, Keith L. Ligon, Susan Weaver, Andrea Laforme, Naren Ramakrishna, Peter McL. Black, Jan Drappatz, Abigail Ciampa, Judah Folkman, Mark Kieran, Patrick Y. Wen
Journal: Neuro-Oncology (2008)

We conducted a phase II study of the combination of temozolomide and angiogenesis inhibitors for treating adult patients with newly diagnosed glioblastoma. Patients who had stable disease following standard radiation therapy received temozolomide for 5 days in 28-day cycles, in combination with daily thalidomide and celecoxib. Patients were treated until tumor progression or development of unacceptable toxicity. Four-month progression-free survival (PFS) from study enrollment was the primary end point, and overall survival (OS) was the secondary end point. In addition, we sought to correlate response with O6-methylguanine-DNA methyltransferase promoter methylation status and serum levels of angiogenic peptides. Fifty patients with glioblastoma were enrolled (18 women, 32 men). Median age was 54 years (range, 29–78) and median KPS score was 90 (range, 70–100). From study enrollment, median PFS was 5.9 months (95% confidence interval [CI]: 4.2–8.0) and 4-month PFS was 63% (95% CI: 46%–75%). Median OS was 12.6 months (95% CI: 8.5–16.4) and 1-year OS was 47%. Of the 47 patients evaluable for best response, none had a complete response, five (11%) had partial response, four (9%) had minor response, 22 (47%) had stable disease, and 16 (34%) had progressive disease. Analysis of serial serum samples obtained from 47 patients for four angiogenic peptides failed to show a significant correlation with response or survival for three of the peptides; higher vascular endothelial growth factor levels showed a trend toward correlation with decreased OS (p = 0.07) and PFS (p = 0.09). The addition of celecoxib and thalidomide to adjuvant temozolomide was well tolerated but did not meet the primary end point of improvement of 4-month PFS from study enrollment.
The Clinical Recognition of Congenital Heart Disease
Authors: Otto G. Thilenius
Journal: JAMA (1994)

ABSTRACT Dr Perloffs The Clinical Recognition of Congenital Heart Disease, now in its fourth edition, continues to occupy a unique place among pediatric cardiology textbooks. It addresses the key question, How do I make a diagnosis? and is thus a critical source of information for the pediatrician and the pediatric cardiologist alike. Even for the seasoned cardiologist, the depth of clinical information, clarity of writing, and superb photographs are a source of knowledge and satisfaction. Whereas other texts spend time with embryologic hypotheses or arguments on nomenclature, Dr Perloff reminds us that the jugular venous and carotid pulses are still part of the clinical evaluation and that the phonocardiogram (!) contains useful information. His aim is a text accessible to those with less than expert knowledge of congenital heart disease, which, if we are truly honest, includes all of us.The diagnosis of congenital heart disease is uniquely suitable to a logical,
Autosomal Recessive (Infantile) Polycystic Kidney Disease Demonstrated by Tc-99m DMSA Renal Imaging
Authors: KEVIN P. TRACEY, HO JEN, JAMES B. METCALFE, ALEXANDER J.B. McEWAN
Journal: Clinical Nuclear Medicine (1991)

A neonate with infantile polycystic kidney disease underwent Tc-99m DMSA imaging. The pattern of uptake in infantile polycystic disease is different from the multiple cystic lesions reported in the literature for adult polycystic kidney disease. The infantile pattern of uptake shows large kidneys with diffuse, symmetric localization of the radiopharmaceutical, which seems to be characteristic and may be pathognomonic of the disease process.
Maternal Phenylketonuria and Hyperphenylalaninemia
Authors: Roger R. Lenke, Harvey L. Levy
Journal: New England Journal of Medicine (1980)

Since many women with phenylketonuria (PKU) will have children of their own, we were interested in ascertaining the effect of maternal PKU and hyperphenylalaninemia on the offspring of such women. We reviewed the literature on this subject and obtained additional unpublished data through an international survey. Data were collected on 524 pregnancies in 155 women; in 34 pregnancies a low-phenylalanine diet was begun after or shortly before pregnancy was established. Among untreated pregnancies, the frequencies of mental retardation, microcephaly, and congenital heart disease were greatly increased over those in the normal population, and these increases correlated with the mother's blood levels of phenylalanine. Ninety-five per cent of mothers with blood phenylalanine concentrations of 20 mg per deciliter or higher had at least one mentally retarded child. Bias introduced by case-finding methods cannot explain these results. It is not clear from our review whether dietary treatment begun after conception is helpful, but treatment begun before conception should be evaluated.
Managing multiple morbidity in mid-life: a qualitative study of attitudes to drug use
Authors: Anne Townsend, Kate Hunt, Sally Wyke
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To examine attitudes towards drug use among middle aged respondents with high levels of chronic morbidity. <b>Design</b> Qualitative study with detailed interviews. <b>Setting</b> West of Scotland. <b>Participants</b> 23 men and women aged about 50 years with four or more chronic illnesses. <b>Main outcome measure</b> Participants9 feelings about long term use of drugs to manage chronic multiple morbidity. <b>Results</b> Drugs occupied a central place in the way people managed their comorbidities. Respondents expressed an aversion to taking drugs, despite acknowledging that they depended on drugs to live as “normal” a life as possible. Respondents expressed ambivalence to their drugs in various ways. Firstly, they adopted both regular and more flexible regimens and might adhere to a regular regimen in treating one condition (such as hypertension) while adopting a flexible regimen in relation to others, in response to their experience of symptoms or varying demands of their daily life. Secondly, they expressed reluctance to take drugs, but an inability to be free of them. Thirdly, drugs both facilitated performance of social roles and served as evidence of an inability to perform such roles. <b>Conclusions</b> Insight into the considerable tension experienced by people managing complex drug regimens to manage multiple chronic illness may help medical carers to support self care practices among patients and to optimise concordance in their use of prescribed drugs.
Poorly Controlled Childhood Asthma Is Associated With Increased Bacterial Lipopolysaccharide (LPS) And Expression of Markers of Airway Remodeling In Bronchoalveolar Lavage (BAL)
Authors: P HAUK, M KRAWIEC, J BOGUNIEWICZ, A SCHILTZ, E GOLEVA, A LIU, D LEUNG
Journal: Journal of Allergy and Clinical Immunology (2008)
TWO CASES OF BONE TUMOUR FROM ANCIENT EGYPT
Authors: R. A. Gardner, A. L. Urquhart
Journal: BMJ (1930)

1 MRIDICAL JOURZAIL~~~~~~~~~~~ Mikuliez's digital dilatationi, by means of a gastrotomy, is necessary' anid effective.By rieason of the comparative infrequency of these conditioins, their (deep situation, and the vital structures around them, theil treatmiient calls for special care and skill.I am indebted to Dr. F. J. Mayes for all the radiological work contributied to the diagnosis of my cases.
An Address ON THE INFLUENCE OF THE BRITISH MEDICAL ASSOCIATION IN THE ESTABLISHMENT OF OPHTHALMOLOGY AS A SPECIAL SCIENCE: Delivered before the Section of Ophthalmology of the Annual Meeting, Brighton, 1913
Authors: T. H. Bickerton
Journal: BMJ (1913)

A SPECIAL SCIENCE.ruG.2, T9I3more particular enquiries, and shall thiink myself fortunate if I am the means of putting any one in the way to procure relief ins.o
Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation
Authors: Esko Ruokonen, Ilkka Parviainen, Stephan M. Jakob, Silvia Nunes, Maija Kaukonen, Stephen T. Shepherd, Toni Sarapohja, J. Raymond Bratty, Jukka Takala
Journal: Intensive Care Medicine (2008)
Antibiotics and sudden death in adults taking renin-angiotensin system blockers
Authors: M. Etminan, J. M. Brophy
Journal: BMJ (2014)

Is there a cause for concern?

Adverse drug reactions have been associated with up to 10% of hospital admissions in older adults,1 a considerable number of which involve drug-drug interactions. Traditionally, information about drug-drug interactions was of poor quality, usually isolated case reports or small uncontrolled case series, resulting in much uncertainty about any clinical relevance. In recent years, large administrative databases that are linkable to health outcomes data have allowed investigators to better quantify rare drug-drug interactions and examine their effect on both morbidity and mortality.

In the linked paper (doi:10.1136/bmj.g6196), Fralick and colleagues examined the risk of sudden death in users of both co-trimoxazole and renin-angiotensin system blockers (RASBs), two potassium sparing drugs.2 In an earlier study, the same authors reported that their joint administration was associated with a sevenfold increase in the risk of hyperkalemia induced hospital admission compared with RASB users exposed to other antibiotics.3 

The new paper considers this same cohort of older RASB users from Ontario’s administrative databases, but now extends follow-up to 18 years and uses a nested case-control approach. The authors report adjusted odds ratios describing the risk of …
Major Histocompatibility Complex Class II Expression by Intrinsic Renal Cells Is Required for Crescentic Glomerulonephritis
Authors: Shuo Li, Christian Kurts, Frank Köntgen, Stephen R. Holdsworth, Peter G. Tipping
Journal: The Journal of Experimental Medicine (1998)

The requirement for major histocompatibility complex class II (MHC II) to initiate immune renal injury was studied in a murine model of CD4(+) T cell-dependent crescentic glomerulonephritis (GN). C57BL/6 (MHC II+/+) mice developed crescentic GN with glomerular CD4(+) T cell infiltration and renal injury, in response to a nephritogenic antigen (sheep globulin) planted on their glomerular basement membrane. MHC II-deficient C57BL/6 mice (MHC II-/-) did not develop crescentic GN, CD4(+) T cell infiltration, or injury, indicating that this form of immune glomerular injury is MHC II dependent. The requirement for MHC II expression by intrinsic renal cells was studied in chimeric mice, which expressed MHC II on bone marrow-derived cells and in the thymus, but not in the kidneys. These chimeric mice had normal T and B cell populations and MHC II expression in their spleens and lymph nodes and developed an immune response to systemically and cutaneously administered sheep globulin. However, they did not develop crescentic GN, CD4(+) T cell infiltration, or renal injury in response to the sheep globulin planted in their glomeruli. These studies demonstrate that interaction of CD4(+) T cells with intrinsic renal cells expressing MHC II is required for development of cell-mediated immune renal injury.
Adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil in Node-Positive Breast Cancer — The Results of 20 Years of Follow-up
Authors: Gianni Bonadonna, Pinuccia Valagussa, Angela Moliterni, Milvia Zambetti, Cristina Brambilla
Journal: New England Journal of Medicine (1995)

Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil was administered after radical mastectomy for primary breast cancer with histologically positive axillary lymph nodes to assess whether it would improve treatment outcome as compared with surgery alone. Here we report a 20-year follow-up of this investigation.
Comparison of Three Methods for Treatment of Congenital Clubfoot
Authors: N. E. Shaw
Journal: BMJ (1966)

Ulcerative Colitis-Bean MEDBCALJOURNAL and carcinoma of the colon, and it may not be too far-fetched to suggest a common cause.Megakaryocytes and platelets have been shown to play an important part in viral multiplication in certain forms of cancer in animals (de Harven and Friend, 1960;Gross, 1963), and more recently thrombocytosis has been reported in human cancer (Levin and Conley, 1964).My own observations are in agreement with the views of the latter worker.In these circumstances the immune-suppressant role of these drugs may well be a disadvantage, and perhaps provide an explanation for both the failure of these drugs to cure and the severity of the relapses.The beneficial action of the drugs could then be attributed to an antiviral action.Further support for this view comes from recent observations on cancer chemotherapy in animals (Groupe and Rauscher, 1965) and the therapy of Burkitt's lymphoma in man (Burkitt et al., 1965).Summary Observations on a small group of patients suffering from ulcerative colitis and treated with antimetabolites are reported.While the effect of chemotherapy is at times dramatic, the successful use of the drugs requires adequate facilities and careful control.While most patients have shown a steady return to normal in all parameters, the failure to achieve cure has been disappointing.The role of the platelet is discussed, and it is suggested that these observations support a viral infection rather than an autoimmune basis for the disease.
Total Cancer Incidence and Overall Mortality Are Not Increased Among Patients With Barrett's Esophagus
Authors: Leo J. Schouten, Jessie Steevens, Clément J.R. Huysentruyt, Ceciel E. Coffeng, Yolande C.A. Keulemans, Floor E. van Leeuwen, Ann L.C. Driessen, Piet A. van den Brandt
Journal: Clinical Gastroenterology and Hepatology (2011)
Complement (C5-a)-induced granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia.
Authors: P R Craddock, D Hammerschmidt, J G White, A P Dalmosso, H S Jacob
Journal: Journal of Clinical Investigation (1977)

Activated plasma complement will induce biphasic aggregation of human granulocytes dectable by standard nephelometric techniques. The responsible active component was suggested to be C5a by molecular weight and heat-stability assays; moreover, aggragating activity was ablated by anti-C5 but not anti-C3 antibodies. C5a prepared by trypsinization of purified C5 reproduced the aggregating activity of whole activated plasma, whereas plasma from a C5-deficient donor did not support aggregation. Embolization of granulocyte aggregates might be a previously unsuspected cause of leukostasis and pulmonary damage in various clinical situations where intravascular complement activation occurs.
Abnormal Development and Function of B Lymphocytes in Mice Deficient for the Signaling Adaptor Protein SLP-65
Authors: Hassan Jumaa, Bernd Wollscheid, Michael Mitterer, Jürgen Wienands, Michael Reth, Peter J Nielsen
Journal: Immunity (1999)

During signal transduction through the B cell antigen receptor (BCR), several signaling elements are brought together by the adaptor protein SLP-65. We have investigated the role of SLP-65 in B cell maturation and function in mice deficient for SLP-65. While the mice are viable, B cell development is affected at several stages. SLP-65-deficient mice show increased proportions of pre-B cells in the bone marrow and immature B cells in peripheral lymphoid organs. B1 B cells are lacking. The mice show lower IgM and IgG3 serum titers and poor IgM but normal IgG immune responses. Mutant B cells show reduced Ca2+ mobilization and reduced proliferative responses to B cell mitogens. We conclude that while playing an important role, SLP-65 is not always required for signaling from the BCR.
Cyborg: Evolution of the Superman
Authors: Saulius Vydas
Journal: JAMA (1965)

D. S. Halacy defines  as a man who uses machines to increase his power; cyborg was born when humans began to make tools, no matter how primitive. Cyborg applies equally well to a laborer using an ordinary shovel and to an investigator handling radioactive material by manipulating giant pincers. The term even includes people with pacemakers, nylon blood vessels, and reinforced bones. The author does not limit himself only to surgery; he also writes about psychic drugs, myo-electric control, hypothermia, tissue culture, and space medicine.  Mankind's attempts to conquer space remind the author of the primitive aquatic organisms struggling to survive on dry land. In both instances, great difficulties had to be overcome. The author believes that engineering alone cannot solve all the problems of space travel. He argues that physicians may have to modify the human body if it is to survive extraterrestrial conditions. For example, hypothermia would
Comparing methods for assessing bronchial responsiveness in children: single step cold air challenge, multiple step cold air challenge, and histamine provocation
Authors: M Modl, E Eber, B Steinbrugger, E Weinhandl, MS Zach
Journal: European Respiratory Journal (1995)

Cold air challenge (CACh) can be applied by either a single step (SSCACh) or a multiple step (MSCACh) protocol. The interrelationship of the responses of the different protocols has not yet been studied. Furthermore, there is contradictory information on the correlation of cold air challenge responses to the outcome of pharmacological provocations. A single and a multiple step cold air challenge and a histamine provocation were performed in random order on three consecutive days on 28 children and adolescents with bronchial asthma, who were currently symptom- and medication-free. Single step cold air challenge consisted of a 4 min isocapnic hyperventilation of dry, -10 degrees C air; the subjects's response was quantified by the induced change in forced expiratory volume in one second (FEV1). Multiple step cold air challenge consisted of a series of 3 min, cold dry air hyperventilation steps from 20 to 80% of maximal voluntary ventilation (MVV); response was expressed as the provocative dose causing a 10% fall in FEV1 (PD10). Histamine provocation consisted of a series of 2 min inhalations of stepwise increasing histamine concentrations from 0.03 to 8.0 mg.mL-1; response was expressed as the provocative concentration of histamine causing a 20% fall in FEV1 (PC20). Change in FEV1 (delta FEV1) (SSCACh) correlated closely with PD10 (MSCACh); scatter around the regression line was minimal. With one exception, both types of CACh identified the same subjects as hyper- and normoresponsive. delta FEV1 (SSCACh) correlated significantly to PC20 (histamine), but scatter around the regression line was substantial. The correlation of PD10 (MSCACh) to PC20 (histamine) failed to reach statistical significance. These results indicate that the stimulus applied and the bronchoconstrictor mechanism activated, and not the challenge protocol, determine the outcome of a cold air challenge. In clinical practice, a brief single step cold air challenge can substitute for a more time-consuming multiple step cold air challenge. As nonpharmacological challenges seem to measure a different type of bronchial responsiveness, neither a single step nor a multiple step cold air challenge can substitute for a pharmacological provocation.