tbuckley/cabot-search huggingface dataset:
United Kingdom Prospective Diabetes Study 17: A 9-Year Update of a Randomized, Controlled Trial on the Effect of Improved Metabolic Control on Complications in Non-Insulin-dependent Diabetes Mellitus
Authors: Robert Turner
Journal: Annals of Internal Medicine (1996)

Purpose: To report the progress (after 9-year follow-up) of a study designed to determine whether improved glucose control in patients with newly diagnosed non–insulin-dependent diabetes mellitus (NIDDM) is effective in reducing the incidence of clinical complications. Data Source: A multicenter, randomized, controlled trial of different therapies for NIDDM. After initial diet therapy, 4209 asymptomatic patients who remained hyperglycemic (fasting plasma glucose levels, 6.0 to 15.0 mmol/L) were assigned to either a conventional therapy policy, primarily with diet alone, or to an intensive therapy policy, aiming for fasting plasma glucose levels of less than 6.0 mmol/L, with assignment to primary therapy with sulfonylurea or insulin (which increased insulin supply) or metformin (which enhanced insulin sensitivity). Results: All three modes of pharmacologic therapy in the intensively treated group—sulfonylurea, insulin, and metformin—had similar efficacy in reducing the fasting plasma glucose and glycated hemoglobin levels. Over 9 years, patients assigned to intensive therapy with sulfonylurea or insulin had lower fasting plasma glucose levels (median, 7.3 and 9.0 mmol/L, respectively) and lower hemoglobin A1c levels (6.7% and 7.5%, respectively) than patients assigned to conventional therapy. Regardless of the assigned therapy, however, the fasting plasma glucose and hemoglobin A1c levels increased, and maintaining near-normal glycemia was, in general, not feasible. Even insulin therapy did not achieve the therapeutic goal of near-normal glycemia because of the difficulty in treating marked hyperglycemia and the risk for hypoglycemic episodes. Nine years after the diagnosis of diabetes, 29% of the patients had had a diabetes-related clinical end point, 20% had had a macrovascular complication, and 9% had had a microvascular complication. Conclusions: A report will be published in 1998 after a median duration from randomization of 11 years (range, 6 to 20 years) with an 81% power at a 1% level of significance of detecting whether the obtained improvement in glucose control causes a 15% decrease or increase in the incidence of major complications and whether any specific therapy is advantageous or disadvantageous.
On the role of phosphatidylethanolamine in the inhibition of activated protein C activity by antiphospholipid antibodies.
Authors: M D Smirnov, D T Triplett, P C Comp, N L Esmon, C T Esmon
Journal: Journal of Clinical Investigation (1995)

Phosphatidylethanolamine (PE) is an important membrane component for supporting activated protein C anticoagulant activity but has little influence on prothrombin activation. This difference constitutes a potential mechanism for selective inhibition of the protein C anticoagulant pathway by lupus anticoagulants and/or antiphospholipid antibodies. In this study, we demonstrate that the presence of PE augments lupus anticoagulant activity. In the plasma of some patients with lupus anticoagulants, activated protein C anticoagulant activity is more potently inhibited than prothrombin activation. As a result, in the presence of activated protein C and PE, these patient plasmas clot faster than normal plasma. Patients with minimal lupus anticoagulant activity are identified whose plasma potently inhibits activated protein C anticoagulant activity. This process is also PE dependent. In three patient plasmas, these phenomena are shown to be due to immunoglobulins. The PE requirement in the expression of activated protein C anticoagulant activity and the PE dependence of some antiphospholipid antibodies provide a mechanistic basis for the selective inhibition of the protein C pathway. Inhibition of activated protein C function may be a common mechanism contributing to increased thrombotic risk in certain patients with antiphospholipid antibodies.
Primary Empty Sella and Rieger's Anomaly of the Anterior Chamber of the Eye
Authors: Richard E. Kleinmann, Edward L. Kazarian, Vassilios Raptopoulos, Lewis E. Braverman
Journal: New England Journal of Medicine (1981)

EXTENSION of the subarachnoid space into the sella turcica, in the absence of prior radiotherapy or surgery, is referred to as primary empty sella. In most patients with this anomaly, the sella is diffusely enlarged and pituitary function is normal.1 2 3 4 Of major clinical importance in primary empty sella is the differentiation of this condition from a pituitary tumor. Most patients with the primary-empty-sella syndrome have been obese, middle-aged women.1 2 3 4 The condition is rarely familial,5 , 6 and it is infrequently observed in children.5 6 7 This report describes a kindred in which primary empty sella was transmitted as an autosomal-dominant trait in association with . . .
REMARKS on the TREATMENT of BACKWARD DISLOCATION of the THUMB (FIRST PHALANX)
Authors: J. Hutchinson
Journal: BMJ (1898)

to the London Hospital.THE literature on this subject is already so abundant that it may be doubted whether there is room for anything further to be written which shall be of practical value.Besides in- numerable papers in the Medical Journals and Transactions, there are over twenty monographs in French and German on Dislocation of the Thumb to reward the search of the in- dustrious reader, and nearly all of them are concerned with the most common form namely, the backward dislocation of the first phalanx, and the cause of the trouble such displace- ment sometimes gives to the surgeon.Two of the papers may be singled out as being of special value: one, an ex- tremely full account (well illustrated) by M. Farabeuf, of Paris; the other, some valuable lectures by Mr. Battle, re-
Developmental effects after inhalation exposure of gravid rabbits and rats to ethylene glycol monoethyl ether.
Authors: F D Andrew, B D Hardin
Journal: Environmental Health Perspectives (1984)

The effects of ethylene glycol monoethyl ether (EGEE) were determined on development in utero. Pregnant New Zealand White rabbits were exposed to air or 160 or 617 ppm EGEE for 7 hr/day from 1 to 18 days of gestation (dg). Virgin Wistar rats were exposed to 150 or 649 ppm EGEE or air 5 days/week for the 3 weeks immediately preceding their breeding. Sperm-positive rats were subsequently exposed to air or 202 or 767 ppm EGEE for 7 hr/day from 1 to 19 dg. Group sizes were 29 to 38 per concentration for both species. Pregestational exposure of rats had no effect on mating success, and there was no effect of EGEE exposure on establishment of pregnancy in either species. Rabbits exposed to the both concentrations had decreased food intake and depressed weight gain. Exposure-related mortality occurred in the 617 ppm EGEE group of rabbits. The only toxic sign seen in rats was reduced weight gain after exposure to 767 ppm EGEE. Exposure induced high embryomortality at maternal toxic concentrations in rats and rabbits, while lower levels induced fetal growth retardation in rats but not in rabbits. Gestational exposure increased the incidence of anomalies and variations; these were primarily of soft tissues in rabbits and of skeleton in rats. Thus, significant evidence of terata, fetal growth retardation and embryomortality were induced in rabbits and rats at levels that were below or similar to those that induced maternal manifestation of toxicity. These data implicate EGEE as a teratogen.
The benefits of inflamed arteries
Authors: Mitch Leslie
Journal: The Journal of Experimental Medicine (2008)

Arterial inflammation can lead to hypertension and heart attacks. But it might also have a good side, according to Tang et al. (page 3159), permitting vessels to adjust their size to match changes in blood flow.






Figure 1

Carotid arteries shrink in response to reduced blood flow (right artery).




In response to changing demands for blood flow, arteries alter their size to maintain constant tension in their walls. They enlarge when more blood is needed, for example in response to organ growth; and they narrow when demand for blood flags, such as in the uterine arteries after birth. Previous studies had shown that inflammation spurs remodeling of the vessel wall in atherosclerosis and hypertension, but whether inflammation also triggered the responses of healthy arteries to changes in blood flow was not certain.

To test this idea, the team partially tied off one branch of the carotid artery in mice, cutting blood flow by roughly half. Downstream from this obstruction, the artery narrowed by about 10–15%, and smooth muscle cells disappeared to prevent the vessel wall from thickening. The revamping vessel also showed clear signs of inflammation. Cells of the arterial wall churned out inflammation-promoting cytokines and chemokines, drawing in macrophages and other leukocytes. Destroying the animals' macrophages thwarted the restructuring.

Neither inflammation nor remodeling could occur without MyD88, an adaptor protein necessary for cytokine production in response to IL-1 or Toll-like receptor signals. The researchers also discovered that this type of arterial inflammation clears up after about two weeks, which might explain why previous studies didn't detect it.
High Promoter Methylation Levels of <i>APC</i> Predict Poor Prognosis in Sextant Biopsies from Prostate Cancer Patients
Authors: Rui Henrique, Franclim R. Ribeiro, Daniel Fonseca, Mohammad O. Hoque, André L. Carvalho, Vera L. Costa, Mafalda Pinto, Jorge Oliveira, Manuel R. Teixeira, David Sidransky, Carmen Jerónimo
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Prostate cancer is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. Owing to the limitations of current clinical, serologic, and pathologic parameters in predicting disease progression, we sought to investigate the prognostic value of promoter methylation of a small panel of genes by quantitative methylation-specific PCR (QMSP) in prostate biopsies. Experimental Design: Promoter methylation levels of APC, CCND2, GSTP1, RARB2, and RASSF1A were determined by QMSP in a prospective series of 83 prostate cancer patients submitted to sextant biopsy. Clinicopathologic data [age, serum prostate-specific antigen (PSA), stage, and Gleason score] and time to progression and/or death from prostate cancer were correlated with methylation findings. Log-rank test and Cox regression model were used to identify which epigenetic markers were independent predictors of prognosis. Results: At a median follow-up time of 45 months, 15 (18%) patients died from prostate cancer, and 37 (45%) patients had recurrent disease. In univariate analysis, stage and hypermethylation of APC were significantly associated with worse disease–specific survival, whereas stage, Gleason score, high diagnostic serum PSA levels, and hypermethylation of APC, GSTP1, and RASSF1A were significantly associated with poor disease-free survival. However, in the final multivariate analysis, only clinical stage and high methylation of APC were significantly and independently associated with unfavorable prognosis, i.e., decreased disease-free and disease-specific survival. Conclusions: High-level APC promoter methylation is an independent predictor of poor prognosis in prostate biopsy samples and might provide relevant prognostic information for patient management.
Elevated skeletal muscle irisin precursor FNDC5 mRNA in obese OLETF rats
Authors: Michael D. Roberts, David S. Bayless, Joseph M. Company, Nathan T. Jenkins, Jaume Padilla, Thomas E. Childs, Jeffrey S. Martin, Vincent J. Dalbo, Frank W. Booth, R. Scott Rector, M. Harold Laughlin
Journal: Metabolism (2013)
Triage in accident and emergency departments
Authors: A. B Bindman
Journal: BMJ (1995)

Triage practices in accident and emergency departments evolved from the military procedure of giving priority for medical care to those who were expected to benefit the most. The focus of triage in many accident and emergency departments today, however, is less on discriminating among the sickest patients and more on identifying patients who may not need emergency care at all. The high cost of care in an accident and emergency department and long waiting times, which result in substantial numbers of patients leaving without being seen, have led to increased scrutiny of this clinical department.1 In the United States the growth in the use of accident and emergency departments has been attributed largely to the increase in the number of people without a regular source of primary care.2 In the United Kingdom the problem is not so much a lack of primary care providers but that these providers may not be technologically or organisationally equipped to evaluate and manage a number of acute problems.3 Investigators and policymakers in both countries …
P15.06 * QUALITY OF PATIENTS LIFE WITH METASTATIC TUMORS OF THE SPINE AND SPINAL CORD
Authors: S. G. Gazieva, N. Tolibova, S. Niyozova, A. Prokhorova
Journal: Neuro-Oncology (2014)

Reducing pain, regression of neurological symptoms, restoration of pelvic organs, restoring lost function of the spinal cord is the primary goal of palliative treatment of patients with metastatic tumors of the spine and spinal cord. PURPOSE: To improve the quality of patients life with metastatic tumors of the spine and spinal cord, differentiated by the choice of treatment In RSCN in the period from 1996 to 2013 years 112 patients were operated on. Of these, 20 patients underwent dorsion stabilizing operation rear access to the establishment of pedicle fixation system, 10 patients dorsion stabilizing operation of anterolateral access, 14 patients underwent percutaneous vertebroplastics with bone cement, 68 patients underwent laminectomy. Before and after surgery quality of life was assessed by the Karnofsky scale. At the time of discharge on the quality of life of patients operated as follow s: 74 patients with a good result (a measure of quality of life - 70 % and more), 28 patients with satisfactory results (quality of life score - 60 %), 8 patients with unsatisfactory results of quality of life - <40 %. CONCLUSIONS: The analysis of the results of surgical treatment of differentiated showed that by reducing pain, regression of neurological symptoms, restoration of pelvic organs allows patients to get rid of nursing care that leads to improved quality of life.
On the Salubrity of Different Places on the North-West Coast
Authors: T. Gibson
Journal: BMJ (1872)

an inch."The question of rapid dilatation is one of great importance, and Dr. Duncan has done good service in drawing attention to it.Tents, of whatever substance they may be made, often produce disagreeable, and sometimes fatal, symptoms.Should, however, rapid dilatation be eventually preferred to the slower process, the instrument used must be one capable of being passed through a stricture without force, and afterwards, by some mechanical contrivance, made to expand so as to act in a direct manner upon the constricted tube.It must be done by art, and not by force.
Additivity of Pyrethroid Actions on Sodium Influx in Cerebrocortical Neurons in Primary Culture
Authors: Zhengyu Cao, Timothy J. Shafer, Kevin M. Crofton, Chris Gennings, Thomas F. Murray
Journal: Environmental Health Perspectives (2011)

Background: Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Although previous work has tested the additivity of pyrethroids in vivo, this has not been assessed directly at the primary molecular target using a functional measure.Objectives: We investigated the potency and efficacy of 11 structurally diverse food-use pyrethroids to evoke sodium (Na+) influx in neurons and tested the hypothesis of dose additivity for a mixture of these same 11 compounds.Methods: We determined pyrethroid-induced increases in Na+ influx in primary cultures of cerebrocortical neurons using the Na+-sensitive dye sodium-binding benzofuran isophthalate (SBFI). Concentration-dependent responses for 11 pyrethroids were determined, and the response to dilutions of a mixture of all 11 compounds at an equimolar mixing ratio was assessed. Additivity was tested assuming a dose-additive model.Results: Seven pyrethroids produced concentration-dependent, tetrodotoxin-sensitive Na+ influx. The rank order of potency was deltamethrin > S-bioallethrin > β-cyfluthrin > λ-cyhalothrin > esfenvalerate > tefluthrin > fenpropathrin. Cypermethrin and bifenthrin produced modest increases in Na+ influx, whereas permethrin and resmethrin were inactive. When all 11 pyrethroids were present at an equimolar mixing ratio, their actions on Na+ influx were consistent with a dose-additive model.Conclusions: These data provide in vitro relative potency and efficacy measurements for 7 pyrethroid compounds in intact mammalian neurons. Despite differences in individual compound potencies, we found the action of a mixture of all 11 pyrethroids to be additive when we used an appropriate statistical model. These results are consistent with a previous report of the additivity of pyrethroids in vivo.
In Vitro Responses of Human Peripheral Small Arteries in Hypercholesterolemia and Effects of Therapy
Authors: Grahame K. Goode, Anthony M. Heagerty
Journal: Circulation (1995)

Studies in both animals and humans with raised lipid levels have demonstrated abnormalities in vascular function usually manifested by an impairment in endothelium-dependent vasorelaxation. This is believed to be an early event in atheroma formation. There are few data on the effects on vascular function in humans of lowering serum lipids. We conducted a study to investigate the effects of cholesterol reduction on the in vitro function of human peripheral small arteries in middle-aged patients with hypercholesterolemia.Subcutaneous gluteal fat biopsies were taken from 18 hypercholesterolemic (HC) patients (mean +/- SEM serum total cholesterol, 9.7 +/- 0.57 mmol/L) and 16 age- and sex-matched control subjects (mean cholesterol, 4.69 +/- 0.18 mmol/L). Subcutaneous small arteries (internal diameter, < 330 microns) were dissected and mounted on a wire myograph for isometric tension measurements. The HC patients showed impaired relaxation to acetylcholine (10(-9) to 10(-6) mol/L) after preconstriction with the thromboxane A2 analogue U46619 (10(-6) mol/L, mean maximum relaxation, 42.9 +/- 5.4%) compared with control subjects (85.7 +/- 4.0%, P < .00001). Incubation with the nitric oxide substrate L-arginine (3 mmol/L) improved the endothelium-dependent vasorelaxation response to acetylcholine (70.9 +/- 6.0%, P < .01) in patients but not in control subjects. Also, there was a smaller but significant difference in responses to the endothelium-independent agent sodium nitroprusside (10(-9) to 10(-6) mol/L) between the HC group (mean maximum relaxation, 76.9 +/- 6.0%) and the control subjects (89.7 +/- 6%; P < .01). A total of 10 patients had a second gluteal skin biopsy and repeat functional studies after successful cholesterol-lowering therapy after a mean period of 9.9 +/- 4.7 months. A significant reduction in total and LDL cholesterol was achieved (5.29 +/- 0.2 and 3.23 +/- 0.21 mmol/L, respectively; P < .001). This restored vasorelaxation to control values in response to both acetylcholine (mean maximum relaxation, 83.3 +/- 3.8%; P < .0001) and sodium nitroprusside (87.9 +/- 4.8%, P < .01). Although both groups were normotensive, there were significantly higher blood pressures in the HC group compared with control subjects (139 +/- 4.1 versus 123 +/- 3.0 mm Hg systolic, P < .01; 84 +/- 1.3 versus 75 +/- 2.2 mm Hg diastolic, P < .01). There was no difference in initial blood pressures between the entire group of 18 and the 10 patients who had repeat biopsies. The blood pressures fell to control values after cholesterol reduction (129.33 +/- 4.93 mm Hg systolic and 72.33 +/- 2.93 diastolic mm Hg, P < .02 relative to pretreatment values).These results demonstrate abnormalities of both endothelium-dependent and -independent relaxation in human peripheral small arteries that are normalized with effective lipid lowering. The changes in blood pressure may have been secondary to the improvement in vascular function.
Cost of Drugs-Reply
Authors: Leo E. Hollister
Journal: JAMA (1976)

In Reply.—  Since Dr Webb pointed out the obvious discrepancies in some figures I quoted about the use of psychotherapeutic drugs, I've been unable to track down the source of these figures, at least without an inordinate amount of effort.  His point is well taken. Any figures are likely to be crude estimates. I once heard a commissioner of the Food and Drug Administration estimate that the total amount spent for drugs in the United States each year was somewhere between $6.5 and $9 billion (he thought $8 billion to be the best guess) and that the ratio of prescription to over-the-counter drugs might vary from 40% to 60% (he thought 50% was reasonable). Obviously, all figures are suspect, and one must carefully scrutinize one's sources. I appreciate having this lapse called to my attention.
Teenage Throwaways: How Many?-Reply
Authors: Richard C. Hermann
Journal: JAMA (1988)

In Reply.—  The Larkin Street article quoted the executive director of the American College of Preventive Medicine, William M. Kane, PhD, as saying an estimated 1 million teenagers run away annually and 125 000 to 250 000 adolescents are involved in prostitution. I confirmed these statistics with established sources in the field of adolescent health.  The Department of Health and Human Services (DHHS), in a 1985 report to Congress, 1 estimated the number of runaway youth at more than one million in the course of the year. The figure is based on the 1976 National Statistical Survey on Runaway Youth 2 and is updated based upon the estimates of knowledgeable experts in the field.  In 1983, the DHHS Office of the Inspector General conducted a nationwide sample study, 3 which from survey responses estimated 558 000 runaway and homeless youth in the United States. The report concluded as follows: Both
Disorders of Language. Ciba Foundation Symposium
Authors: Donald P. Granger, Russell Meyers
Journal: JAMA (1964)

The title, unfortunately, is somewhat misleading, since the contents deal almost entirely with aphasia and certain symbolic disorders closely pertinent thereto. The book does not deal with varieties of dysphonia, dysarthria, dyslalia, stammering, stuttering, and other disorders of language. Much less does it deal with semantic disorders concerning the gaps between neurology, psychology, psychiatry, and sociology. However, regarding the aphasic disorders it is a commendable product. A novice would become familiar with the important historical developments and current concepts relevant to the subject. An expert would find little that has not already appeared in the literature, but would appreciate the economical review and the brave effort at critical evaluation not hitherto attempted. Most of the old controversies receive considerable notice. The strong trend of the present symposium favors a topographic atomization of the several emissive and receptive language processes. Regrettably, the only advocate of a dynamic, monolithic view of aphasia