tbuckley/cabot-search huggingface dataset:
Molecular mechanisms of leukocyte recruitment in the inflammatory process
Authors: K. Ley
Journal: Cardiovascular Research (1996)

The microcirculation constitutes the functional interface between the circulating blood and the interstitial space. To gain access to sites of inflammation, leukocytes must pass the endothelial barrier. The recruitment paradigm encompasses leukocyte margination, capture, rolling, activation, firm adhesion, and transmigration. Recent experimental work has shown that E-, L- and P-selectins and alpha 4 integrins can mediate leukocyte rolling. Upon activation by chemokines, complement peptides or lipid mediators, firm adhesion is afforded by beta 1 and beta 2 integrins, InterCellular Adhesion Molecules (ICAMs) and Vascular Cell Adhesion Molecule-1 (VCAM-1). Beta 1 and beta 2 integrins as well as Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1) have been shown to be involved in transmigration. Intravital microscopic techniques have been instrumental in applying the conceptual advances of cell and molecular biology to the in vivo situation. This review focuses on the current understanding of the leukocyte recruitment paradigm as suggested by in vivo observations and in vitro model systems. The paradigm of neutrophil recruitment is presented to serve as a model for the recruitment mechanisms of other inflammatory cells.
Restriction fragment length polymorphism in the interzeta hypervariable region for prenatal diagnosis of non‐deletion α thalassemia
Authors: Vivian Chan, T. K. Chan, A. C. K. Wong, T. P. T. Chan, A. Ghosh, D. Todd
Journal: American Journal of Hematology (1988)

Abstract A Bam HI restriction fragment length polymorphism in the interzeta hypervariable region (IZ HVR) of the ζ‐α gene cluster was used for the prenatal diagnosis of a pregnancy at risk for Hb H hydrops fetalis. The parents had ζ‐α thalassemia 1 and non‐deletion α thalassemia, respectively, and a previous hydrops was missed using the conventional method of gene detection. In this prenatal diagnosis, linkage to IZ HVR was used to exclude non‐deletion α thalassemia, and the numbers of ζ and α genes in the fetus were quantitated to predict the exact genotype. Confirmation was made by analysis of cord blood at delivery.
A CLINICAL STUDY OF HYPERPHORIA.
Authors: JOHN T. CARPENTER
Journal: JAMA (1898)

The importance of recognizing and correcting with absolute accuracy, any existing error of refraction, has long since become an axiom, a truth too evident to require demonstration. In the past decade, mainly as a result of careful clinical study, errors of muscular balance have been attracting the attention of the ophthalmic surgeon; but in this field there still exist wide differences of opinion both as to the importance of muscular defects and the necessity for their treatment. One may find almost anything desired by searching the literature of this subject. If he be naturally conservative he may read of that wonderful and unfailing "cure-all" for muscular imbalance, prismatic exercise. The method of cure is both simple in its application and positively harmless. It is even monotonous in the uniformity of its good results. On the other hand, should the ophthalmologist be surgically inclined; should his desire be to refute the
Shall The Journal be Removed to Washington?
Authors: None Reader
Journal: JAMA (1891)

<h3>To the Editor:</h3> —Being a reader ofThe Journaland interested in the question of its removal from the old stand, I was curious enough to figure out the number of subscribers (members) in the principal Eastern cities as compared with those in the West, and I<i>find Chicago leads them all</i>. The number of subscribers (members) in the Eastern cities is as follows: Philadelphia 109, Washington 82, New York 77, Baltimore 35, Brooklyn 25, and Boston 33, making a total of 361 copies distributed in six cities with a population of<i>nearly five millions</i>. In the Western cities: Chicago 171, Cincinnati 83, St. Louis 79, Louisville 24, Detroit 28, and Cleveland 20, making a total of 405 subscribers (members) in six cities of a population of about<i>two and a half million</i>. The Eastern States make the following showing: Pennsylvania 397, New York 234, Massachusetts 121, New Jersey 55,
Studies on the origin of faecal amino acids in cystic fibrosis
Authors: J. W. T. Seakins, R. S. Ersser, I. S. E. Gibbons
Journal: Gut (1970)

Evidence is presented which demonstrates that excess faecal amino acids in cystic fibrosis are derived from unabsorbed dietary protein. Changes in the absorption of fat and nitrogen have little effect on the amino-acid patterns.
Determination of Specific IgG Antibody by Crossed Radioimmunoelectrophoresis
Authors: S. L. Nordvall, T. Uhlin, R. Einarsson
Journal: Allergy (1983)

A crossed radioimmunoelectrophoretic method was developed for detection of honey bee venom specific IgG antibodies in patient sera. At the serum concentration 1/200 the contrast between specific binding and background was the most favourable. The detection limit was fairly low, approximately 30 kU/1 (IgG RAST units). A reference system based on the reference kits in Phadebas IgG‐RAST® was elaborated.
Fish and Chemicals: The Process of Accumulation
Authors: J L Hamelink, A Spacie
Journal: The Annual Review of Pharmacology and Toxicology (1977)

After three decades (1, 2) of intensive research, the environmental behavior of DDT is still almost incomprehensible. Consider for a moment that fish can easily accumu­ late a million times the concentration of DDT found in the water they inhabit. Yet, incredible as it may seem, fish are doing that every day with DDT and several other interesting compounds. At the same time, there are numerous other chemicals they cannot bioaccumulate with such efficiency. These associations constitute the subject for this review. Fish and chemicals-how does the one accumulate the other? The effects of pollutants on fish have been comprehensively reviewed annually since 1968 (3a-h) in the Journal a/the Water Pollution Control Federation. Johnson has published two critical reviews (4, 5) dealing with pesticides and fish that are
Management of kidney stones
Authors: Nicole L Miller, James E Lingeman
Journal: BMJ (2007)

Urolithiasis affects 5-15% of the population worldwide.1 w1 Recurrence rates are close to 50%,2 w2 and the cost of urolithiasis to individuals and society is high. Acute renal colic is a common presentation in general practice, so a basic understanding of its evaluation and treatment would be useful. Most of the literature is retrospective, but we will try to provide an evidence based review of the management of urolithiasis and will cite prospective randomised controlled trials when available.

#### Summary points

#### Sources and selection criteria

Initial evaluation of the patient with urolithiasis should include a complete medical history and physical examination. Typical symptoms of acute renal colic are intermittent colicky flank pain that may radiate to the lower abdomen or groin, often associated with nausea and vomiting.3 Lower urinary tract symptoms such as dysuria, urgency, and frequency may occur once a stone enters the ureter.

Comorbid diseases should be identified, particularly any systemic illnesses that might increase the risk of kidney stone formation or that might influence the clinical course of the disease (box 1). Other important features are a …
A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease
Authors: Rashid Deane, Itender Singh, Abhay P. Sagare, Robert D. Bell, Nathan T. Ross, Barbra LaRue, Rachal Love, Sheldon Perry, Nicole Paquette, Richard J. Deane, Meenakshisundaram Thiyagarajan, Troy Zarcone, Gunter Fritz, Alan E. Friedman, Benjamin L. Miller, Berislav V. Zlokovic
Journal: Journal of Clinical Investigation (2012)

In Alzheimer disease (AD), amyloid β peptide (Aβ) accumulates in plaques in the brain. Receptor for advanced glycation end products (RAGE) mediates Aβ-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo. FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB). In aged APPsw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibited RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited β-secretase activity and Aβ production and suppressed microglia activation and the neuroinflammatory response. Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly and normalized cognitive performance and cerebral blood flow responses in aged APPsw/0 mice. Our data suggest that FPS-ZM1 is a potent multimodal RAGE blocker that effectively controls progression of Aβ-mediated brain disorder and that it may have the potential to be a disease-modifying agent for AD.
Helping the General Medical Council
Authors: K. Channer
Journal: BMJ (2000)

See also pp 61, 69, and 122 

I was a trainee in cardiology in Bristol at the time of the events leading to the disciplinary action against two cardiac surgeons and the chief executive over the deaths of children after cardiac surgery. These events have questioned the role of professional self regulation and the General Medical Council (GMC) has developed new procedures to assess performance. I volunteered to pilot the procedures. I thought that, as I had been in post for 10 years, an independent assessment of my work could help me reassess how I do things.

The procedures help to identify the doctor whose performance is below standard so that improvements can be targeted. Before the team arrived on site I was asked to complete a detailed portfolio. I described what time was committed to teaching, training, and research, together with a full explanation of the clinical sessions I undertook in the NHS and in private practice.

> I still do not know if I am a good doctor 

There were questions about my attitude to …
TECHNIQUE IN TÆNIA TREATMENT—REPORT OF A REMARKABLE CASE.
Authors: C. M. FENN
Journal: JAMA (1894)

In the absence hitherto of any unfailing tænicides or specifics, it may be profitable to inquire if there are any other methods available for the safe and certain expulsion of the various cestodes. Personally, having abandoned the search for such a remedy, for the reason that it might imperil the well-being of host as well as guest, I find that some of the standard tæniafuges, if employed in adequate doses and supplemented by attention to certain details, to be noted farther on, may be made to accomplish all that we desire. For example, during the local prevalence of tape-worms which followed the importation of a measly herd from Mexico, some years ago, I came to use kameela in doses of 8 to 12 grains ([unk]ii-[unk]iii), and ethereal extract of male-fern to the extent of 4 to 10 grams [unk]i-[unk]iiss). These apparently large doses, exceeding those recommended by the authorities of
Genetic Tumor Markers With Prognostic Impact in Dukes’ Stages B and C Colorectal Cancer Patients
Authors: Chieu B. Diep, Lin Thorstensen, Gunn Iren Meling, Eva Skovlund, Torleiv O. Rognum, Ragnhild A. Lothe
Journal: Journal of Clinical Oncology (2003)

To examine several genetic changes in primary colorectal carcinomas (CRCs) from patients with 10 years of follow-up and associate the findings with clinicopathologic variables.DNA from 220 CRCs were analyzed for allelic imbalances at 12 loci on chromosome arms 1p, 14q, 17p, 18q, and 20q, and the microsatellite instability (MSI) status was determined. The clinical significance of the tumor protein 53 (TP53) mutations was re-evaluated.Patients with tumors containing 17p or 18q deletions had shorter survival than those without these alterations (P =.021, P =.008, respectively). This was also significant for the Dukes' B group (P =.025, P =.010, respectively). Furthermore, patients with tumors showing losses of both chromosome arms revealed an even poorer disease outcome than those with either 17p or 18q loss. Patients with low increase in 20q copy number in their tumors had longer survival compared with those without changes (P =.009) or those with a high increase of copy number (P =.037). This was also evident for the Dukes' C group (P =.018, P =.030, respectively). MSI was seemingly a beneficial marker for survival (P =.071). A significant association between mutations affecting the L3 zinc-binding domain of TP53 and survival was confirmed in this cohort after 10 years of follow-up, and also was found to apply for patients in the Dukes' B group. Several associations were found among genetic and pathologic data.The present study indicates that 17p, 18q, and 20q genotypes, and TP53 mutation status add information in the subclassification of Dukes' B and C patients and may have impact on the choice of treatment.
VII. The Painfully Slow Progress in Medical Education
Authors: Lester S. King
Journal: JAMA (1983)

In 1847 the American Medical Association had already described some of the defects in the American medical scene, particularly in medical education. The convention had three major areas of complaint: the preliminary education of those who wanted to study medicine, the actual courses of instruction at the medical schools, and the examinations to be taken before the medical student could join the ranks of active practitioners. Today, we may observe parenthetically, the same three areas are still the subject of debate: What<i>is</i>the best preliminary education for those intending to study medicine? How can the curriculum be improved? What system of examination will best ensure competence? Today's answers, still in flux, show a lineal connection with the same problem areas of the 19th century. In its initial organization, the AMA wisely established several standing committees to provide better means for studying some major problems. The committee on education has
The Thymus: Experimental and Clinical Studies
Authors: Kurt Stern
Journal: JAMA (1967)

This three-day symposium on the thymus was a veritable "summit meeting," as reflected in participants, contents, and scope of treatment. Investigations utilizing the modern biotechnology of electron microscopy, histochemistry, immunochemistry, cytogenetics, and tissue culture have provided significant information on the physiologic role of the thymus in lymphopoiesis and the development of cellular and humoral immunologic capacities. Elaborate experimental designs that have been brought to bear on suitable animal models have furnished support for the participation of the thymus in the pathogenesis of autoimmune diseases and in some forms of carcinogenesis and leukemogenesis, especially those initiated by viruses or ionizing radiation. Another group of presentations deals expertly with human diseases now acknowledged as caused by thymic lesions or associated therewith, including genetic dysplasias of the organ, genetic or acquired immunologic deficiencies, thymoma associated with myasthenia gravis or with pure red cell anemia, thymic changes in systemic lupus erythematosus, and in some
Intensive Replacement of Basal Insulin in Patients With Type 1 Diabetes Given Rapid-Acting Insulin Analog at Mealtime
Authors: Paolo Rossetti, Simone Pampanelli, Carmine Fanelli, Francesca Porcellati, Emanuela Costa, Elisabetta Torlone, Luciano Scionti, Geremia B. Bolli
Journal: Diabetes Care (2003)

OBJECTIVE—To establish differences in blood glucose between different regimens of optimized basal insulin substitution in type 1 diabetic patients given lispro insulin at meals, i.e., NPH injected four times a day versus glargine insulin once daily at dinner or at bedtime. RESEARCH DESIGN AND METHODS—A total of 51 patients with type 1 diabetes on intensive therapy (NPH four times/day and lispro insulin at each meal) were randomized to three different regimens of basal insulin substitution while continuing lispro insulin at meals: continuation of NPH four times/day (n = 17), once daily glargine at dinnertime (n = 17), and once daily glargine at bedtime (n = 17) for 3 months. Blood glucose targets were fasting, preprandial, and bedtime concentrations at 6.4–7.2 mmol/l and 2 h after meals at 8.0–9.2 mmol/l. The primary end point was HbA1c. RESULTS—Mean daily blood glucose was lower with dinnertime glargine (7.5 ± 0.2 mmol/l) or bedtime glargine (7.4 ± 0.2 mmol/l) versus NPH (8.3 ± 0.2 mmol/l) (P &amp;lt; 0.05). A greater percentage of blood glucose values were at the target value with glargine at dinner and bedtime versus those with NPH (P &amp;lt; 0.05). HbA1c at 3 months did not change with NPH but decreased with glargine at dinnertime (from 6.8 ± 0.2 to 6.4 ± 0.1%) and glargine at bedtime (from 7.0 ± 0.2 to 6.6 ± 0.1%) (P &amp;lt; 0.04 vs. NPH). Total daily insulin doses were similar with the three treatments, but with glargine there was an increase in basal and a decrease in mealtime insulin requirements (P &amp;lt; 0.05). Frequency of mild hypoglycemia (self-assisted episodes, blood glucose ≤4.0 mmol/l) was lower with glargine (dinnertime 8.1 ± 0.8 mmol/l, bedtime 7.7 ± 0.9 mmol/l) than with NPH (12.2 ± 1.3 mmol/l) (episodes/patient-month, P &amp;lt; 0.04). In-hospital profiles confirmed outpatient blood glucose data and indicated more steady plasma insulin concentrations at night and before meals with glargine versus NPH (P &amp;lt; 0.05). There were no differences between glargine given at dinnertime and at bedtime. CONCLUSIONS—Regimens of basal insulin with either NPH four times/day or glargine once/day in type 1 diabetic patients both result in good glycemic control. However, the simpler glargine regimen decreases the HbA1c level and frequency of hypoglycemia versus NPH. In contrast to NPH, which should be given at bedtime, insulin glargine can be administered at dinnertime without deteriorating blood glucose control.
Evidence for Stimulation of Renal Gluconeogenesis by Catecholamines
Authors: Kiyoshi Kurokawa, Shaul G. Massry
Journal: Journal of Clinical Investigation (1973)

Isoproterenol and norepinephrine (10-4 M) significantly increased cyclic AMP formation and glucose production by the isolated tubules of the renal cortex of the rat. These effects were abolished by propranolol. Theophylline diminished the effects of the catecholamines on gluconeogenesis despite a marked augmentation in cyclic AMP concentration. In the absence of calcium ion in the incubation medium, isoproterenol stimulates cyclic AMP production, but has no effect on gluconeogenesis. It is concluded that catecholamines enhance gluconeogenesis in renal cortical tubules by the stimulation of beta adrenergic receptors. This effect is probably mediated through adenyl cyclase-cyclic AMP system and requires an adequate level of ATP and the presence of calcium ion.
A child with neck swelling
Authors: I. P. Sinha, A. Stickland, C. M. John
Journal: BMJ (2012)

A 5 year old boy presents with neck swelling and sore throat. He appears pale and tired, and has a 2 cm left sided neck swelling. You should distinguish cervical lymphadenopathy secondary to local causes from other important diagnoses (box). #### Differential diagnosis of neck swellings in children ##### Lymphadenopathy (enlarged lymph nodes) ###### Local causes ###### Systemic causes ##### Lymphadenitis (inflamed lymph nodes) or abscess ##### Non-lymphadenomatous neck swellings ### Important features in the history
THE EVIDENCE OF INSANITY; AN OUTLINE.
Authors: J. SANDERSON CHRISTISON
Journal: JAMA (1896)

<h3>GENERAL CONSIDERATIONS.</h3> The whole question of insanity hinges on the<i>origin</i>, the<i>support</i>and the<i>display</i>of ideas. Its pathology has nothing distinctly characteristic, being merely a measure of functional incompetence whatever the coexistent facts. But as all motion is potential in ideas, ideation has its equivalent in molecular change and thus mental aberration has its physiologic concomitants. No mortal can be said to be free from errors of fact or opinion of one kind or another, but comparatively few resist demonstration—logical, or objective refutation. An idea that does not fit with popular belief is not necessarily a delusion. Indeed, if it does not clash with any demonstrable principle or particular fact, it can not be regarded as a delusion, for we have no other means of proving it false than by such evidence. It may be an intuitive prophecy or the product of a genius. The grand steps of
Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation
Authors: Chiao-Yin Sun, Shih-Chung Chang, Mai-Szu Wu
Journal: Kidney International (2012)

The expression of the renoprotective antiaging gene Klotho is decreased in uremia. Recent studies suggest that Klotho may be a tumor suppressor, and its expression may be repressed by DNA hypermethylation in cancer cells. Here we investigated the effects and possible mechanisms by which Klotho expression is regulated during uremia in uninephrectomized B-6 mice given the uremic toxins indoxyl sulfate or p-cresyl sulfate. Cultured human renal tubular HK2 cells treated with these toxins were used as an in vitro model. Injections of indoxyl sulfate or p-cresyl sulfate increased their serum concentrations, kidney fibrosis, CpG hypermethylation of the Klotho gene, and decreased Klotho expression in renal tubules of these mice. The expression of DNA methyltransferases 1, 3a, and 3b isoforms in HK2 cells treated with indoxyl sulfate or p-cresyl sulfate was significantly increased. Specific inhibition of DNA methyltransferase isoform 1 by 5-aza-2'-deoxycytidine caused demethylation of the Klotho gene and increased Klotho expression in vitro. Thus, inhibition of Klotho gene expression by uremic toxins correlates with gene hypermethylation, suggesting that epigenetic modification of specific genes by uremic toxins may be an important pathological mechanism of disease.
Making access to health care more equal
Authors: G. Bevan, J. Charlton
Journal: BMJ (1987)

Making access to health care more equal SIR,-I have difficulty in understanding the costing in the paper by Messrs Gwyn Bevan and John Charlton (26 September, p 764).Table I refers to a mean expenditure by family practitioner com- mittees on medical services per head of £6.76 in 1980-1.In 1981 the gross expenditure on general medical services was £16 per head.'Over 90% would be revenue.Moreover, general medical practitioners incur a far greater expenditure from pharma- ceuticals-£23 per head.A fairer comparison of the contribution of the family practitioner committee budget to total medical expenditure would be £39 per head per year compared with £148 per head for hospital services.
Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells
Authors: Elly De Vlieghere, Félix Gremonprez, Laurine Verset, Lore Mariën, Christopher J. Jones, Bram De Craene, Geert Berx, Benedicte Descamps, Christian Vanhove, Jean-Paul Remon, Wim Ceelen, Pieter Demetter, Marc Bracke, Bruno G. De Geest, Olivier De Wever
Journal: Biomaterials (2015)
Acute Vascular Ischemic Events After Cisplatin-Based Combination Chemotherapy for Germ-Cell Tumors of the Testis
Authors: DONALD C. DOLL
Journal: Annals of Internal Medicine (1986)

Four patients with germ-cell tumors of the testis had acute vascular ischemic events after treatment with cisplatin-based combination chemotherapy. Two patients had myocardial infarctions and two others cerebrovascular accidents. All patients were less than 30 years old and had no significant risk factors for atherosclerotic cardiovascular disease. Angiographic studies done in three patients showed no endovascular abnormalities. Raynaud's phenomenon preceded acute myocardial infarction in one patient with angiographic evidence of ergonovine-induced coronary artery spasm. We suggest that major arterial occlusive events may occur as a result of treatment with cisplatin-based combination chemotherapy.