tbuckley/cabot-search huggingface dataset:
Status of Medical Officers in the Volunteer Army.
Authors: Nelson M. Black
Journal: JAMA (1900)

Milwaukee, Dec. 20, 1900. <h3>To the Editor:</h3> —I desire through the columns ofThe Journalto communicate with the gentlemen who served in the Volunteer Army with State Volunteers during the war with Spain and who held the rank of captain and assistant-surgeon. These gentlemen were commissioned captains by authority of the act of April, 1898, calling into service volunteer armies. They were paid as first lieutenants, in accordance with a decision of the comptroller of the currency. Notwithstanding this, they are undoubtedly entitled to the pay of the rank, that of captain mounted, as is evidenced by the wording of the Law of Congress and the opinion of the surgeon-general and adjutant-general in respect to the law which was passed giving the captains and assistant-surgeons of the volunteers raised under the act of March 2, 1899, the pay of their rank. It will be necessary, however, to induce Congress
Exocytosis in normal anterior pituitary cells. Quantitative correlation between growth hormone release and the morphological features of exocytosis.
Authors: B Draznin, R Dahl, N Sherman, K E Sussman, L A Staehelin
Journal: Journal of Clinical Investigation (1988)

We have used high-pressure freezing techniques to study exocytosis in rat anterior pituitary cells. The cells were either unstimulated or exposed to 1 nM growth hormone releasing factor (GRF) for 10 min before ultrarapid freezing. The magnitude of growth hormone (GH) release was then correlated with the number of exocytotic events observed with freeze-fracture electron microscopy. High-pressure freezing of unfixed and uncryoprotected specimens permits cryofixation of samples up to 1 mm diam (0.5 mm thick) without ice crystal damage, and arrests exocytotic events within 10 ms. Our studies comparing conventionally fixed specimens with those prepared by high-pressure freezing confirm that areas of intramembrane particle clearing at potential exocytotic sites are an artifact of conventional fixation and/or cryoprotection techniques. The cells exposed to 1 nM GRF released approximately fivefold more GH than did unstimulated cells. Morphologically, we have observed a 3.3-fold increase in the number of exocytotic events in GRF-stimulated cells, 33.7 events/100 micron2 compared with 10.4 events/100 micron2 for unstimulated cells. In additional experiments, we studied the effects of two inhibitors of GRF-induced exocytosis, somatostatin and sodium isethionate. Both compounds elicit the same response, a parallel decrease in exocytotic events and in secreted product. We conclude that high-pressure freezing, combined with freeze-fracture and freeze-substitution processing techniques, is an excellent tool for studying the morphological aspects of exocytosis. In the present investigation, it has allowed us to quantitatively relate the biochemistry and morphology of exocytosis in anterior pituitary cells.
Revalidation proposals will waste time
Authors: L. Beecham
Journal: BMJ (2001)

While continuing to support the principle of revalidation, the BMA has resolved that the current proposals from the General Medical Council would waste time and clinical skills, which would be better spent on direct patient care.

Although all the BMA sections support the idea that doctors need to show, at regular intervals, that they are competent to continue in practice, the chairman of the Junior Doctors Committee, Dr Trevor Pickersgill, …
815. Aerosol Delivery of Helper-Dependent Adenoviral Vector into Nonhuman Primate Lungs Results in High Efficiency Pulmonary Transduction with Minimal Toxicity
Authors: Peter Hiatt, Nicola Brunetti-Pierri, David Koehler, Ruth McConnell, Julie Katkin, Donna Palmer, David Dimmock, Jim Hu, Milton Finegold, Arthur Beaudet, Dee Carey, Karen Rice, Philip Ng
Journal: Molecular Therapy (2005)

Cystic fibrosis is caused by recessive mutations in a membrane chloride channel gene (CFTR) expressed in the airway epithelium and is characterized by persistent, progressive inflammation and infection, eventually leading to lung failure. A major obstacle to CF gene therapy is inefficient pulmonary transduction by viral and nonviral vectors in large animals and humans. To address this obstacle, we have used a novel strategy for efficient aerosol delivery into nonhuman primate lungs of a helper-dependent adenoviral vector (HDAd) bearing a human airway epithelial cell and submucosal gland cell-specific expression cassette driving LacZ. The AeroProbe, an intracorporeal nebulizing catheter, was used to aerosolize 1.67|[times]|1011 vp/kg of the HDAd formulated in 0.45 ml/kg of 0.1% L-a-lysophosphatidylcholine (LPC) directly into the airways of three baboons at a rate of 0.6 ml/min. Extensive and unprecedented high levels of transduction of the ciliated epithelium of the trachea, bronchi and bronchioles as well as submucosal glands were observed in all three baboons. No respiratory distress was noted for all three animals following vector administration. Chest X-rays revealed no abnormalities at 6, 48 and 72 hours post-administration for two animals. Minimal infiltrate at the site of bronchoscopy was noted in the third animal. Laboratory findings (chemistries, cell counts, cytokines, etc) in the blood and BAL fluid were unremarkable. Histological examination at 72 hours post-administration revealed only mild and patchy subclinical pneumonia in all three animals. This study demonstrates a novel and promising strategy to achieve high efficiency transduction of the trachea, the proximal and distal airway epithelium and submucosal glands in a large animal model for HDAd-mediated, lung-directed gene therapy for CF.
FOXO3A DEFICIENCY AND VIRAL LOAD IN ACUTE COXSACKIEVIRUS B3 MYOCARDITIS: ROLE OF NK CELL FUNCTION
Authors: Carsten Skurk, Madlen Loebel, Luise Holzhauser, Moritz Becher, Sandra Pinkert, Heinz-Peter Schultheiss, Carmen Scheibenbogen
Journal: Journal of the American College of Cardiology (2013)
Can Mirizzi Syndrome be Classified into Acute and Chronic Form?: An Endoscopic Retrograde Cholangiography (ERC) Study
Authors: A. Morelli, F. Narducci, R. Ciccone
Journal: Endoscopy (1978)

Three cases of Mirizzi syndrome (partial mechanical obstruction of the common hepatic duct owing to compression by a stone impacted in the cystic duct or gallbladder neck, or due to the inflammatory reaction resulting from compression) are reported. The roentgen features at endoscopic retrograde cholangiography (ERC) are discussed. As there are two causes for obstruction, compression or chronic fibrosing reaction resulting from compression, two characteristic X-ray findings and two operating techniques, the authors contend that Mirizzi syndrome should be classified as acute or chronic.
Role of androgens in the aetiology of rheumatoid arthritis.
Authors: P Brennan, A Silman
Journal: Annals of the Rheumatic Diseases (1996)

Table 1 Clinicalfeatures ofpatients with or without clinical relapse Without clinical relapse With clinical relapse (n = 11) (n = 9) Age (y) 75-1 (8-3) 75-6 (7 6) Sexratio (M:F) 1:10 4:5 Diseases 9 PMR 8 PMR 2 GCA 1 GCA Disease duration (months) 57 8 (51 4) 51-4 (43-7) Prednisone dose (mg/day) Initial 19 7 (8 4) 16-8 (6) Before reduction 3 9 (1 9) 5 (2-1) After reduction 1-8 (1-1) 2-1 (1-4) Values are mean (SD).PMR = Polymyalgia rheumatica; GCA = giant cell arteritis.
Experimental cobalt cardiomyopathy: correlation between electrocardiography and pathology
Authors: H. C. Grice, H. A. Heggtveit, G. S. Wiberg, G. Van Petten, R. Willes
Journal: Cardiovascular Research (1970)

Indwelling electrodes were implanted in rats one week before intraperitoneal injections of cardiotoxic doses of cobalt. Electrocardiograms were recorded from the rats at varying time intervals after dosing. The rats were subsequently killed and their hearts were examined histologically. The topography and histological characteristics of the cardiac lesion were established and were compared with alterations in the electrocardiogram.
Persistent T-wave changes after alteration of the ventricular activation sequence. New insights into cellular mechanisms of 'cardiac memory'.
Authors: J C Geller, M R Rosen
Journal: Circulation (1993)

BACKGROUND "Cardiac memory" refers to persistent T-wave changes on ECG that follow resumption of sinus rhythm after a period of altered activation sequence. Previous studies demonstrated that cardiac memory in intact dogs was abolished by 4-aminopyridine (4-AP), which blocks both the transient outward potassium current, Ito, and IK. METHODS AND RESULTS We used standard microelectrode techniques to study the mechanism for cardiac memory in canine ventricular subepicardial and subendocardial slabs measuring 15 x 30 x 1 to 2 mm. Bipolar electrodes were used to stimulate slabs parallel to fiber axis, simulating normal activation, and perpendicular to fiber axis, simulating ventricular pacing. Four 30-minute periods of normal activation at a basic cycle length of 650 milliseconds were interrupted by three 20-minute periods of ventricular pacing at a basic cycle length of 450 milliseconds. We first recorded action potentials differentially from epicardial and endocardial slabs. The stimulation protocol induced changes in the "T" wave of the difference signals that mimicked cardiac memory and that could be explained on the basis of the transmural gradient in repolarization between epicardium and endocardium. This result was not obtainable with slow and rapid pacing from one site only. In subsequent experiments, action potential characteristics of epicardial and endocardial slabs were studied by the same pacing protocol with alternation between simulated normal activation and ventricular pacing. During ventricular pacing, the epicardial phase 1 notch and plateau amplitude decreased compared with normal activation. 4-AP (3 mmol/L) decreased notch size and plateau amplitude during normal activation in epicardium but not endocardium. In contrast, the local anesthetic lidocaine did not change notch size or plateau amplitude in epicardium or endocardium. CONCLUSIONS These results suggest that the contribution to repolarization of specific potassium channels influences the memory phenomenon and that by blocking Ito and reducing the transmural voltage gradient for repolarization, 4-AP abolishes cardiac memory.
AIDS: Reason for Optimism?-Reply
Authors: Janice Westenhouse
Journal: JAMA (1993)

<h3>In Reply.</h3> —In his essay, Bayer states, "The looming crisis in health care for those with HIV disease set the stage for congressional action that could scarcely have been imagined a short time earlier." Although initial budget cuts may have dampened Bayer's hopes for change, perhaps he should have been more optimistic about the choices the American public was ready to make. President Clinton was elected in no small part because of his views on reform of health care organization and financing, and he has recently promised additional funding for the Ryan White Act. We believe that the nation is turning the corner on health care not only for those infected with HIV, but for all persons.
Progestin therapy of breast cancer: comparison of agents.
Authors: B. A. Stoll
Journal: BMJ (1967)

Squint-Adelstein and Scully not explain the trend.We can only speculate on factors such as subclinical infections, or length of daylight. SummaryWe report an analysis of 3,243 cases of squint examined at a health department clinic and an eye hospital.The estimated prevalence of squint at the age of 6 years is 4.3%, similar to estimates in other surveys in England.Incidence of onset is highest in the third year of life, and, if this distribution reflects the incidence in the community, it represents one characteristic pattern of distribution.Another pattern has been described in which the highest rate of onset is in the first year and diminishes rapidly thereafter.Non-central viewing occurs in 23% of the cases of squint in which this function could be assessed.Non-central viewing is much more frequent in boys, in children in whom the onset is early, in those who have had the squint for a longer period, and in those with high degrees of anisometropia.There is evidence that squints begin more often in winter, with a peak incidence in January.We are indebted to Mrs. Anne Fish for her painstaking and careful handling of the data, 'and to Professor C. I. Phillips for his advice.We wish to
Directly observed treatment for tuberculosis
Authors: P. Garner
Journal: BMJ (2003)

Less faith, more science would be helpful 

Drugs cure tuberculosis. So why does the disease remain in the top 10 causes of global mortality, with 1.8 million deaths a year?1 Most deaths are in low and middle income countries, where a major challenge is to ensure that drugs are available and people complete the long treatment. The World Health Organization has been tackling the global problem of inadequate tuberculosis control for some years and launched a new programme of integrated care in 1994, called directly observed treatment, short course (DOTS).2 By using a six month course of drugs, including rifampicin, WHO has mobilised money, people, and systems in countries to tackle the global problem with good progress.3 Its strategy is divided into five key aspects: political commitment, access to sputum microscopy, short course chemotherapy using direct observation …
Short-term outcome of critically ill patients with severe acute respiratory syndrome
Authors: Charles D. Gomersall, Gavin M. Joynt, Philip Lam, Thomas Li, Florence Yap, Doris Lam, Thomas A. Buckley, Joseph J. Y. Sung, David S. Hui, Gregory E. Antonio, Anil T. Ahuja, Patricia Leung
Journal: Intensive Care Medicine (2004)

To document the outcome and determine prognostic factors for patients with severe acute respiratory syndrome who require admission to an intensive care unit.
Effect of formulation variables on in vitro release of a water-soluble drug from chitosan–sodium alginate matrix tablets
Authors: Liang Li, Jinfeng Li, Shanshan Si, Linlin Wang, Chenjun Shi, Yujiao Sun, Zhenglin Liang, Shirui Mao
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The objective of this study is to investigate the feasibility of using chitosan–sodium alginate (CS–SA) based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables. Using trimetazidine hydrochloride (TH) as a water-soluble model drug, influence of dissolution medium, the amount of CS–SA, the CS:SA ratio, the type of SA, the type and amount of diluents, on in vitro drug release from CS–SA based matrix tablets were studied. Drug release kinetics and release mechanisms were elucidated. In vitro release experiments were conducted in simulated gastric fluid (SGF) followed by simulated intestinal fluid (SIF). Drug release rate decreased with the increase of CS–SA amount. CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found. On the other hand, a large amount of water-soluble diluents could modify drug release profiles. It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism. In conclusion, this study demonstrated that it is possible to design extended-release tablets of water-soluble drugs using CS–SA as the matrix by optimizing formulation components, and provide better understanding about drug release from CS–SA matrix tablets.
Abstract B31: Potential for patient tailoring for prodrug of gemcitabine (LY2334737) by assessment carboxylesterase II expression in solid tumor biopsies
Authors: Timothy R. Holzer, Kathleen Heinz-Taheny, Darryl W. Ballard, Eric L. Powell, Marisa P. Dolled-Filhart, Jason Christiansen, Mark Gustavson, Jennifer Biryukov, Jagatheswari Virayah, Susan E. Pratt, Robert L. Shepard, Sara C. Durland- Busbice, Anne H. Dantzig
Journal: Clinical Cancer Research (2010)

Abstract Carboxylesterase II (CES2), a serine ester hydrolase, is the major carboxylesterase responsible for the conversion of the prodrug of gemcitabine into its active form, gemcitabine (LY2334737), an anticancer chemotherapeutic. In humans, the ratio of plasma levels of prodrug to active form is 10:1. Therefore, increased availability of LY2334737 can result in cleavage of the prodrug into its active form at the tumor site and has potential for greater tumor cytotoxicity. Relatively high levels of expression of CES2 within non-neoplastic human tissue occur in the liver, kidney and gastrointestinal tract as visualized by immunohistochemistry (IHC). CES2 is also reported to be expressed in human cancers such as non-small cell lung carcinoma and colon adenocarcinomas. In this study, we analyzed CES2- transfected in vitro cell lines by real-time PCR, chromogenic IHC, and automated quantitative analysis (AQUA) of immunofluorescent in situ protein expression and showed that high levels of CES2 correlate with higher cytotoxicity. qRT-PCR analysis revealed that the mRNA levels of CES2 measured in formalin-fixed paraffin-embedded tumors correlate with protein levels. CES2 transcriptional profiling was performed to identify additional tumor types with high levels of expression of CES2. CES2 overexpression was detectable by IHC and/or AQUA analysis in human colon carcinoma, mesothelioma, non-small cell lung cancer, and tumors of the breast and ovary. CES2 IHC labeling in colonic adenocarcinomas was diffuse. However, labeling in non-neoplastic mucosa showed low levels in proliferating cells at the crypt base and increasingly higher expression toward the terminally differentiated cells at the tips—cells that would not progress through the cell cycle and should not be affected by antiproliferative agents. In conclusion, we have developed robust IHC and AQUA-based assays for differential expression of CES protein levels in a variety of archival human tumor types and have shown high correlation with CES2 transcript levels by qRT-PCR. These methodologies can identify tumors with high levels of CES2, a biomarker that may further be investigated in biomarker-driven clinical trials to identify patients who will more likely respond to LY2334737. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B31.
EXERCISE TOLERANCE IN HEART DISEASE
Authors: THEODORE B. BARRINGER
Journal: JAMA (1922)

Exercise tolerance, a term generally used the last few years in connection with heart disease, expresses a new idea which has done much to illuminate an obscure section of cardiac diagnosis and prognosis. The implications of this idea are far-reaching and not yet fully appreciated. It puts before us the conception that we can best judge of the heart's capacity or reserve power by observing the way exercise is tolerated rather than by various other procedures. The capacity for physical exercise is undoubtedly a valid criterion of the condition of the heart's efficiency, because the capacity for exercise depends essentially on the heart's ability to increase its output, provided the lungs, the nervous system and the skeletal muscles are functioning in a normal manner. This is a most important statement, the truth of which is not generally recognized. An essential function of the heart is to furnish an adequate supply
Hospitals and GPs must tell patients about incidents that cause "moderate" as well as "serious" harm, report says
Authors: C. Dyer
Journal: BMJ (2014)

NHS healthcare providers in England should be obliged to tell patients of incidents that cause moderate harm, as well as those that result in serious harm or death, an expert review set up by the government has recommended.1

Jeremy Hunt, England’s health secretary, asked Norman Williams, president of the Royal College of Surgeons, and David Dalton, chief executive of Salford Royal NHS Foundation Trust, to look at how far the proposed new duty of candour should extend.

A new obligation on organisations that provide care to tell patients when things go wrong was recommended by the public inquiry into systemic failures at Mid Staffordshire NHS Foundation Trust. Robert Francis QC’s report recommended that …
Study finds that most drug donations to developing countries are appropriate
Authors: J. Ciment
Journal: BMJ (1999)

In the most extensive study of drug donations to date, a team of American researchers has concluded that most drugs donated by US pharmaceutical companies and delivered by private voluntary organisations are appropriate for local medical needs and arrive well before their expiry dates.

The Harvard School of Public Health's study An Assessment of US Pharmaceutical Donations: Players, Processes, and Products noted that 58-90% of drugs donated in three sample countries—Armenia, Haiti, and Tanzania—ere on either the respective countries' essential drugs list or the World Health Organisation's “model” list.

Examining data …
Cardiovascular Responses Following Immunological Sympathectomy
Authors: MICHAEL J. BRODY, Richard A. Shaffer
Journal: Circulation Research (1964)

Sympathetic function and cardiovascular responses were measured in rats treated at birth with an antiserum developed to the sympathetic nerve growth factor. The intact animals exhibited ptosis, miosis, and decreased excretion of norepinephrine in the urine. Electrical stimulation of the sympathetic innervation to the vessels of the perfused hindquarters failed to produce vasoconstriction or vasodilatation in any of the treated rats over a wide range of stimulus parameters. Alterations in vascular reactivity characteristic of sympathetic denervation were noted; responsiveness was increased to norepinephrine but not to other constrictor agents. Chemical stimulation of the sympathetic ganglia with 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) did not activate the postganglionic fibers but did promote the release of catecholamines from the adrenal medulla. The treated rats showed elevated resistance to flow in the hindquarters. The results of this investigation thus demonstrate that treatment with the antinerve growth factor effectively abolishes vasomotor function of the fibers of the sympathetic nervous system.
Editorial: Much hope but little proof
Authors: Z. Danilevicius
Journal: JAMA (1976)

The thought that specific antiplatelet therapy might improve cardiovascular function and exercise performance of patients with coronary heart disease has provoked lively discussion. Frishman et al<sup>1</sup>found that untreated patients with ischemic myocardial disease had increased platelet aggregability when compared to normal persons. After these patients were treated with aspirin, platelet release of adenosine diphosphate (ADP) in response to aggregating agents was abolished both in patients and in normal persons, completely inhibiting aggregation. No increased exercise tolerance, however, was observed in patients with ischemic heart disease who were taking aspirin. Weiss<sup>2</sup>reviewed all antiplatelet drugs used in prevention of thrombosis. He considers aspirin to be the most effective drug in inhibiting platelet aggregation. Sulfinpyrazone sodium, administered in therapeutic doses over a period of several weeks, prolongs platelet survival time and reduces platelet turnover in man. Clofibrate, especially when administered with anticoagulants, reduces platelet adhesion in patients with ischemic