tbuckley/cabot-search huggingface dataset:
Dose response effectiveness of propranolol for the treatment of angina pectoris.
Authors: E L Alderman, R O Davies, J J Crowley, M G Lopes, J Z Brooker, J P Friedman, A F Graham, H J Matlof, D C Harrison
Journal: Circulation (1975)

Seventeen patients received placebo medication during a 12-week run-in period, followed by four double-blind study periods of six weeks each, during which time placebo, 80 mg, 160 mg and 320 mg propranolol dosages were administered. Examination of the frequency of angina episodes and nonprophylactic nitroglycerin consumption revealed significant beneficial clinical responses for both the 160 and 320 mg dosages. Exercise testing also demonstrated increased exercise tolerance (320 mg dose) with a shift of the exercise end point from pain to fatigue in seven of 17 patients. The interrelationships between propranolol daily dosage, clinical response assessed by percent reduction in anginal episodes, beta-adrenergic blockade measured by percent reduction in exercise heart rate and serum levels were examined. In general, serum levels of 30 ng/ml, when drawn 90 to 180 minutes following the last oral dose, were required to achieve a 25% or greater reduction in angina frequency. Serum levels above 30 ng/ml were similarly correlated with a 20% or greater reduction in exercise heart rate at equivalent levels of exercise. Detailed examination of different patterns of clinical response with respect to beta-blockade, serum levels and oral doses are presented.
Study of the −429 T/C and −374 T/A Receptor For Advanced Glycation End Products Promoter Polymorphisms in Diabetic and Nondiabetic Subjects With Macrovascular Disease
Authors: Barry I. Hudson, Max H. Stickland, T. Simon Futers, Peter J. Grant
Journal: Diabetes Care (2001)

The receptor for advanced glycation end products (RAGE) has been implicated in the development of vascular complications of diabetes by both in vitro and in vivo studies (1). The most compelling evidence demonstrated that blocking of AGE/RAGE binding prevented atherosclerotic development in animal models (2). It is plausible that genetic differences in the RAGE gene could alter expression and function to affect disease development. In previous studies, we have identified a number of potentially functional polymorphisms: Gly82Ser in the AGE-binding domain (3) and two common promoter polymorphisms at positions −429 and −374 (4). The Gly82Ser polymorphism was not found to relate …
Scanning electron microscopy of superficial defects in articular cartilage.
Authors: F N Ghadially, R L Ailsby, A F Oryschak
Journal: Annals of the Rheumatic Diseases (1974)

It has long been recognized that the power of articular cartilage to regenerate and repair wounds in its substance is feeble or nonexistent (Hunter, 1743;Paget, 1853).This is largely due to the fact that chondrocytes in the mature
Lithium-induced Hyperpolarization of the Human Rectum in Vivo
Authors: J. Rask-Madsen, P. C. Baastrup, M. Schwartz
Journal: BMJ (1972)

The transmucosal potential difference across the rectal mucosa was measured in 30 healthy subjects and in 13 psychiatric patients on lithium treatment for manic-depressive psychosis. It was significantly greater in the lithium-treated patients. A highly significant correlation was found between the potential difference and the serum lithium, and in all eight patients in whom it was measured before and one week after starting lithium treatment a rising potential difference was found. This phenomenon may possibly be explained in terms of resistance of the rectal mucosa to vasopressin.
James Alexander Culpin MacKeith
Authors: Sebastian Kraemer
Journal: BMJ (2008)

James Alexander Culpin MacKeith (“Jim”) was one of the most courageous forensic psychiatrists of his generation. Over three decades he showed, in the face of some resistance from the legal and psychiatric establishment, how vulnerable individuals could under pressure in police interviews make false confessions. His work with the psychologist Professor Gisli Gudjonsson helped to secure the release of the Guildford Four in 1989, the Birmingham Six in 1991, and Judith Ward in 1992, among others, and led to a full scale review of the criminal justice trial process by the Royal Commission on Criminal Justice (the Runciman commission). …
550. Adenoviral-Mediated Antioxidant Overexpression: Possible Protective Role Against Hyperglycemic Conditions in Human Aortic Endothelial Cells
Authors: Aoife Duffy, Aaron Liew, Afshin Samali, Timothy O'Brien
Journal: Molecular Therapy (2005)

Intoduction: Increased oxidative stress is a well documented characteristic of diabetes mellitus, which plays a key role in the pathogenesis of diabetic vascular dysfunction. An increase in oxygen free radicals (O2-) is believed to be associated with diabetes mellitus. Efficient free radical scavenging is imperative for normal endothelial cell function and survival in diabetes mellitus. As superoxide dismutase (SOD) is responsible for scavenging O2- in eukaryotic cells, the aim of this study was to assess if transducing Human Aortic Enothelial Cells (HAEC) with recombinant adenovirus encoding MnSOD, CuZnSOD and Catalase, could reverse high glucose induced decrease in cell viability. Methods: HAECs exposed to adenoviral vectors encoding MnSOD (AdMnSOD), CuZnSOD (AdCuZnSOD), Catalase (AdCat) or Green Fluorescent Protein (AdGFP) or diluent (control) were cultured in normal glucose (NG)(5.5 mmol/L) or high glucose (HG) (30 mmol/L) medium. Cell viability was assessed by Methlythiazolydiphenyl-tetrazolium bromide (MTT) Assay. Transgene expression was detected by confocal microscopy in AdGFP transduced cells and by Western blot analysis for AdMnSOD/ AdCuZnSOD/ AdCat-transduced cells 48 hours post transduction. Results: From initial non-transduced cell viability assays, HAECs in HG displayed decrease in viability of 14% (n=11, P|[le]|0.01) compared to NG. Under HG conditions, exposure to CuZnSOD and MnSOD resulted in increased cell viability (versus non-transduced controls). Under NG conditions, exposure to MnSOD and CuZnSOD resulted in decreased cell viability (versus non-transduced controls). Catalase reduced viability in NG and HG conditions, but the latter to a lesser extent. Control vector AdGFP had no effect on viability. Conclusion: Decreased viability observed in HAECs under HG conditions can be reversed by overexpression of MnSOD and CuZnSOD. As such, antioxidant overexpression may hold promise in protecting endothelial cells against hyperglycemic conditions.
Discordant Occurrence of Primary Biliary Cirrhosis in Monozygotic Twins
Authors: Marshall M. Kaplan, Arthur R. Rabson, Young-Mee Lee, David L. Williams, Patricia A. Montaperto
Journal: New England Journal of Medicine (1994)

To the Editor: The cause of primary biliary cirrhosis is unknown but may be associated with an inherited abnormality of immune regulation1,2. It is not known whether abnormal genes alone will cause the disease or whether an additional triggering event is needed. Both a genetic abnormality and a triggering event are needed to cause another chronic liver disease, autoimmune chronic active hepatitis3. We report on a pair of monozygotic twins; one was healthy, and the other had advanced primary biliary cirrhosis. The first twin, a 58-year-old woman, had had primary biliary cirrhosis for eight years (Figure 1). . . .
"Spontaneous" Progressive Multifocal Leukoencephalopathy
Authors: ALLAN KNIGHT
Journal: Annals of Internal Medicine (1972)

A 22-year-old man, with the malabsorption syndrome, had deficiencies of both humoral immunity and cell-mediated immunity. Terminally, he developed multifocal neurological abnormalities. Postmortem examination showed progressive multifocal leukoencephalopathy, thymic hypoplasia, and abnormal lymph nodes.
The Outcome of Surgery in Patients More Than 90 Years Old
Authors: Etienne J. Phipps
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The report by Hosking et al<sup>1</sup>raises some perplexing questions about the adequacy and application of survival-based studies that fail to include data about patients' quality of life. As the researchers point out, surgical outcomes, in terms of increased longevity for patients, continue to improve. At the same time, concerns about rising medical care costs, allocation of critical care beds and other valuable resources, and what constitutes medically futile treatment have entered the realm of medical decision making. The bind, so elegantly demonstrated in and by this study, is that medicine (and here more specifically surgery) can keep patients living longer; but by leaving out functional data from the study design, the implication is that these data are not important in ultimately evaluating whether survival is a positive or negative goal.
The H-Y Antigen and Male Sexual Development
Authors: Park S. Gerald
Journal: New England Journal of Medicine (1979)

The aberrations of the male gonads and genitalia range from such common entities as hypospadias and undescended testes to rare and bizarre disorders like hermaphroditism. As is often the case, the cause of the more common disorders has proved to be elusive, but some insight into the rarer entities is being attained from studies of the H-Y antigen. A case in point is the study by Winters and his colleagues in this issue of the Journal. Cases of this kind are worthy of close observation in the hope that the resolution of the rare end of the spectrum of . . .
The Disease Burden Associated With Overweight and Obesity
Authors: Aviva Must
Journal: JAMA (1999)

Overweight and obesity are increasing dramatically in the United States and most likely contribute substantially to the burden of chronic health conditions.To describe the relationship between weight status and prevalence of health conditions by severity of overweight and obesity in the US population.Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III), which was conducted in 2 phases from 1988 to 1994.A total of 16884 adults, 25 years and older, classified as overweight and obese (body mass index [BMI] > or =25 kg/m2) based on National Institutes of Health recommended guidelines.Prevalence of type 2 diabetes mellitus, gallbladder disease, coronary heart disease, high blood cholesterol level, high blood pressure, or osteoarthritis.Sixty-three percent of men and 55% of women had a body mass index of 25 kg/m2 or greater. A graded increase in the prevalence ratio (PR) was observed with increasing severity of overweight and obesity for all of the health outcomes except for coronary heart disease in men and high blood cholesterol level in both men and women. With normal-weight individuals as the reference, for individuals with BMIs of at least 40 kg/m2 and who were younger than 55 years, PRs were highest for type 2 diabetes for men (PR, 18.1; 95% confidence interval [CI], 6.7-46.8) and women (PR, 12.9; 95% CI, 5.7-28.1) and gallbladder disease for men (PR, 21.1; 95% CI, 4.1-84.2) and women (PR, 5.2; 95% CI, 2.9-8.9). Prevalence ratios generally were greater in younger than in older adults. The prevalence of having 2 or more health conditions increased with weight status category across all racial and ethnic subgroups.Based on these results, more than half of all US adults are considered overweight or obese. The prevalence of obesity-related comorbidities emphasizes the need for concerted efforts to prevent and treat obesity rather than just its associated comorbidities.
Conferences should be held where the problems are
Authors: A. R Potter
Journal: BMJ (1999)

Nothing makes my toes curl more than books that promise "200 expert tips" on a subject which your professors foolishly and inexplicably omitted from the curriculum when you were at university.Such books are almost invariably published in north America, written in a slack, simplistic, anti-academic style, and slip unconsciously into jargon when anything
Internal Administration of Antitoxic Sera.
Authors: Edward M. Merrins
Journal: JAMA (1906)

East Orange, N. J., Sept. 21, 1906.  To the Editor:  —May I inquire if any readers ofThe Journalhave administered antitoxic serum in other ways than by subcutaneous injection, and if so, what has been their experience? In England and elsewhere it has been demonstrated clinically that serum given per os or per rectum is effective, yet one seldom or never hears of these methods being practiced in this country. As the question is of considerable practical importance, it may be interesting to refer to some of the literature on the subject which justifies the change of method.  Within the last few days it has been announced that Professor Behring's latest remedy against tuberculosis, called tulase, is about to be given an extensive trial in the hospitals of France and Germany, and, by his direction, it may be introduced into the system either by subcutaneous injection or by swallowing.
Current Status of Intrauterine Devices
Authors: Daniel R. Mishell
Journal: New England Journal of Medicine (1985)

Despite the millions of dollars that have been spent in the past decade by various funding agencies to develop new contraceptive techniques, an ideal contraceptive, one that is completely effective without having adverse effects, has not been produced and will most likely not be developed in this century. Thus, the causal relation between the intrauterine device (IUD) and infertility due to tubal damage, which has been demonstrated by two epidemiologic studies reported in this issue,1 , 2 needs to be assessed in terms of the overall risk–benefit ratio for this method of contraception.The IUD has several major benefits in comparison with . . .
Engineering Clustered Ligand Binding Into Nonviral Vectors: αvβ3 Targeting as an Example
Authors: Quinn KT Ng, Marie K Sutton, Pan Soonsawad, Li Xing, Holland Cheng, Tatiana Segura
Journal: Molecular Therapy (2009)

The development of techniques to efficiently deliver genes using nonviral approaches can broaden the application of gene delivery in medical applications without the safety concerns associated with viral vectors. Here, we designed a clustered integrin-binding platform to enhance the efficiency and targetability of nonviral gene transfer to HeLa cells with low and high densities of alpha(v)beta(3) integrin receptors. Arg-Gly-Asp (RGD) nanoclusters were formed using gold nanoparticles functionalized with RGD peptides and used to modify the surface of DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes with attached RGD nanoclusters resulted in either 5.4- or 35-fold increase in gene transfer efficiency over unmodified polyplexes for HeLa cells with low- or high-integrin surface density, respectively. The transfection efficiency obtained with the commercially available vector jetPEI-RGD was used for comparison as a vector without clustered binding. JetPEI-RGD exhibited a 1.2-fold enhancement compared to unmodified jetPEI in cells with high densities of alpha(v)beta(3) integrin receptors. The data presented here emphasize the importance of the RGD conformational arrangement on the surface of the polyplex to achieve efficient targeting and gene transfer, and provide an approach to introduce clustering to a wide variety of nanoparticles for gene delivery.
Short-term Exercise Training Enhances Reflex Cholinergic Nitric Oxide–Dependent Coronary Vasodilation in Conscious Dogs
Authors: Gong Zhao, Xiaoping Zhang, Xiaobin Xu, Manuel Ochoa, Thomas H. Hintze
Journal: Circulation Research (1997)

Abstract The effects of exercise training on the coronary vasodilation following activation of the Bezold-Jarisch reflex were examined in conscious dogs. Mongrel dogs were chronically instrumented using sterile techniques for measurements of systemic hemodynamics and left circumflex coronary blood flow (CBF). With the heart rate controlled (150 bpm), veratrine (0.5 to 20 μg/kg) caused dose-dependent increases in CBF; eg, 5 μg/kg of veratrine increased CBF by 61±6% from 31±1.3 mL/min ( P &lt;.05). After exercise training, the dose-response curve of CBF in response to veratrine was shifted to the left; eg, 5 μg/kg of veratrine increased CBF by 101±12% ( P &lt;.05 compared with control) from 34±2.3 mL/min. The enhanced coronary vasodilation was blunted by nitro- l -arginine (NLA, 35 mg/kg). In anesthetized dogs after exercise training, electrical stimulation of the left vagus nerve caused greater increases in CBF, and NLA inhibited increases in CBF. Acetylcholine, norepinephrine, angiotensin II, and bradykinin caused greater increases in NO 2 − production in coronary microvessels from exercise-trained dogs compared with those from normal dogs. Our results indicate that the coronary vasodilation following activation of the Bezold-Jarisch reflex is enhanced in conscious dogs after exercise training. Since electrical stimulation of the vagus nerve caused greater coronary vasodilation and since the agonists resulted in greater increases in NO production in coronary microvessels from exercise-trained dogs, the mechanism responsible for the enhanced coronary vasodilation following activation of the Bezold-Jarisch reflex is most likely due to the increased release of NO from the endothelial cells.
Persistent primary enuresis: a urodynamic assessment.
Authors: C G Whiteside, E P Arnold
Journal: BMJ (1975)

Videocystourethrography with synchronous pressure and flow-rate recordings has been carried out on 50 patients referred for the investigation of persistent primary enuresis. Urodynamic studies showed nocturnal enuresis to be associated mainly with normal detrusor function and nocturnal plus diurnal enuresis mainly with abnormal detrusor function. Evidence is presented which suggests that these two distinct types of enuresis occur de novo and do not overlap. Out of 18 of formerly enuretic male patients nine with abnormal detrusor function showed persistent nocturnal plus diurnal symptoms.
170. In Vitro Transduction of Cells To Determine Tropism Using Viral-Like Particles Derived from JC Virus VP1
Authors: Linda Cashion, Oliver Ast, Andrzej Citkowicz, Susan Harvey, Branka Mitrovic, Mary Rose Masikat, Katalin Kauser, Brent Larsen, Gabor M. Rubanyi, Richard N. Harkins, Harald Petry
Journal: Molecular Therapy (2005)

Top of pageAbstract
Gene therapy for treatment of neurological diseases is a rapidly emerging new field. Virus-Like Particles (VLP) originating from the human polyoma virus JCV are being evaluated as a delivery vector for the central nervous system (CNS) because JCV preferentially infects both oligodendrocytes and astrocytes.

In developing a gene delivery system with JCV VLP, we have optimized both the production of recombinant VP1 from JCV in insect cells and the packaging conditions for purified VP1 and plasmid DNA. Using VP1-VLP containing plasmid DNA expressing EGFP, we have performed transduction assays in a panel of human and rodent brain-derived and non-brain derived cells in order to characterize the in vitro tropism and species specificity of VP1-VLP.

From the survey of human brain-derived cell lines, TC620 (oligodendroglioma) had the highest transduction efficiency with VP1-VLP. Up to 80% of the cells were expressing EGFP after transduction in vitro. In these studies, we added 0.3 ng/cell of VP1 protein containing 0.8 |[mu]|g of plasmid DNA to 5x104 cells. SK-N-SH, a human neuroblastoma cell line, and a population of primary normal human astrocytes also showed high transduction efficiencies following treatment with VP1-VLP. The rodent cell line NG108-15, a hybrid between a rat glioma and mouse neuroblastoma, and rat brain primary cells expressed EGFP after treatment with human VP1-VLP. These results demonstrate that VP1-VLP can transduce both human and rodent brain cells, at least in vitro. With the exception of one human prostate cell line (PC-3), significant VP1-VLP transduction was not observed in any non-brain-derived human or rodent cells studied including cell lines from kidney, liver, lung, skeletal muscle, and vascular endothelium. Thus, the VP1-VLP system from JCV may provide an efficient and selective delivery system for therapeutic genes to target specific cells in the brain.
The Theoretical Foundations of Chinese Medicine: Systems of Correspondence
Authors: ILZA Veith
Journal: JAMA (1974)

Western readers may hopefully assume that this book will afford them easy access to the intricacies of Chinese medicine in general, and acupuncture in particular. This, however, is by no means the case, as the book, true to its title, stresses predominantly the<i>theoretical foundations</i>of Chinese medicine, ie, structure and function of the human body as seen from the traditional Chinese point of view. Acupuncture is, of course, also included, as it does belong to Chinese medicine from its very beginning, but it is treated almost coincidentally, without any detailed explanation of technique and purpose. Acupuncture points are listed under the organs that they serve. They are named by their Latin anatomical designations, by their Chinese names in transliteration, as well as by their Chinese ideographs, which clearly denote their original meaning. On the whole, the book assumes a great deal of prior knowledge of Chinese natural philosophy on
Targeting deprived areas within small areas in Scotland: population study
Authors: P. McLoone
Journal: BMJ (2001)

expedited thrombolysis, a time dependent intervention.Over 80% of available patients had a gold standard test in our study.The populations served by an inner city emergency department such as the Manchester Royal Infirmary are highly mobile and diverse; many of the patients who did not return were homeless, non-local, or migrant.Although 100% follow up is desirable, this test was evaluated in a real life population, and exclusion of patients who were not local or those who were homeless would have introduced bias by affecting the spectrum of disease.