tbuckley/cabot-search huggingface dataset:
Effect of an Autonomic Blocking Agent and a Vasopressor on Blood Flow
Authors: Enrique D. David
Journal: JAMA (1961)

SINCE DeBakey and his colleagues clearly demonstrated the role of the borrowing-lending phenomenon in the distribution of blood flow, 1 it should have been evident that vasodilators and autonomic blocking agents have no place in the treatment of localized circulatory impairment due to interruption of blood flow through the arterial stem supplying that segment. Nevertheless, some have continued to use these agents for acute and chronic arterial obstruction. It was the purpose of this study to evaluate the influence of tetraethylammonium (Etamon) chloride and of metaraminol (Aramine) bitartrate upon the arterial pressure distal to an acutely induced arterial block. The method of Longenecker, Reemtsma, and Creech 2 was used.  Materials and Methods  Healthy mongrel dogs were anesthetized by the intravenous injection of thiopental sodium. Tracheal intubation was carried out, and the lungs were rhythmically insufflated with oxygen by means of a mechanical respirator. The dogs were heparinized, and the
Acyclovir-Resistant Varicella Zoster Virus Infection after Chronic Oral Acyclovir Therapy in Patients with the Acquired Immunodeficiency Syndrome (AIDS)
Authors: Mark A. Jacobson
Journal: Annals of Internal Medicine (1990)

Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or highdose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count < 50 cells/ μL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 ¼mol/L for acyclovir, 1.4 compared with 0.8 ¼mol/L for vidarabine, and 123 compared with 117 ¼mol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.
Development of secondary polycythaemia in chronic airways obstruction.
Authors: J R Stradling, D J Lane
Journal: Thorax (1981)

In the current study, we found that a subpopulation of apoptotic T-cells (CD4<sup>+</sup>CD25<sup>+ </sup>and 85% Foxp3<sup>+</sup>) from persons with latent tuberculosis (TB) infection, inhibits growth of <i>M. tuberculosis</i> (<i>M. tb</i>) in human monocyte-derived macrophages (MDMs) from 16.5 ± 1.2 x 10<sup>6 </sup> vs 2.2 ± 1.1 x 10<sup>6 </sup>CFU (p=0.001). Analysis of culture supernatants from T-cells by 2D gel electrophoresis and LC MS/MS indicated that a soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic T-cells is responsible for this inhibition of <i>M.tb</i> growth in MDMs and in mice. <i>M. tb</i>-expanded CD4+CD25+Foxp3+D4GDI+ cells do not produce IL-10, TGF-β and IFN-γ. D4GDI inhibited growth of <i>M. tb </i>from 10.4 ± 1.1 x 10<sup>6 </sup> vs 2.8 ± 0.6 x 10<sup>6 </sup>CFU (p&lt;0.001) and D4GDI siRNA reversed T-cells-dependent <i>M. tb </i>growth inhibition in MDMs from 1.8 ± 0.3 x 10<sup>6 </sup>to 5.5 ± 1 x 10<sup>6 </sup>CFU (p=0.001). D4GDI enhanced production of IL-1β (43 ± 33 to 193 ± 104 pg/ml, p=0.02), TNF-α (88 ± 126 to 129 ± 111 pg/ml, p=0.03) and ROS production and enhanced apoptosis of <i>M. tb</i>-infected MDMs to inhibit <i>M.tb</i> growth. D4GDI was concentrated at the site of disease in TB patients, with higher levels detected in pleural fluid than in serum. However, in response to <i>M. tb</i>, PBMC from TB patients produced less D4GDI than PBMC from persons with LTBI (13.7 ± 9.3 vs. 40.6 ± 3.2, p=0.02). Our study provides the first evidence that a subpopulation of T-cells enhances immunity to <i>M. tb, </i>and that production of D4GDI by this subpopulation inhibits <i>M. tb</i> growth.
LSD and Chromosomes
Authors: Etan Markowitz
Journal: JAMA (1970)

<h3>To the Editor.—</h3> Tjio et al (<b>210:</b>849, 1969) have made an important methodological advance in the study of the effects of lysergic acid diethylamide (LSD) on human chromosomes in vivo by measuring chromosome aberration rates in subjects both before and after LSD administration. The authors were unable to conclude that LSD had a harmful effect. Using more powerful statistical methods, we conclude that LSD has a significantly harmful effect in both dose groups. In testing hypotheses, we have strict control of the (type 1) error of rejecting the null hypothesis when true and little control of the (type 2) error of not rejecting the null hypothesis when false. To minimize the probability of failing to detect a harmful effect and to ensure valid conclusions, one-tailed tests are appropriate.<sup>1</sup> From the data in Table 2 of the communication, the number of normal and aberrant cells in each sample can
LATENT LIVER DISEASE IN PERSONS RECOVERED FROM CATARRHAL JAUNDICE AND IN OTHERWISE NORMAL MEDICAL STUDENTS AS REVEALED BY THE BILIRUBIN EXCRETION TEST
Authors: Arthur Kornberg
Journal: Journal of Clinical Investigation (1942)

The frequency with which chronic non-hemolytic jaundice occurs in otherwise healthy young persons is not commonly recognized, nor 'is it usually appreciated how often an uncomplicated attack of catarrhal jaundice is followed by residual liver dysfunction which persists long after the acute episode.The present study was prompted by the acci- dental discovery of a relatively large number of medical students with chronic jaundice and a history of a previous attack of catarrhal jaundice in two of them.A group of persons long recov- ered from catarrhal jaundice was investigated and also a control group of persons presumably nor- mal.The bilirubin excretion test was used in all cases because of its reliability in detecting lesser degrees of liver dysfunction. METHODSBilirubin excretion test.The method of Von Bergmann and Eilbott (1, 2) was used with modifications.Bilirubin (Eastman Kodak) was given under basal conditions in a dose of 1.5 mgm.per kilogram of body weight.No
Accurate separation of biliary lipid aggregates requires the correct intermixed micellar/intervesicular bile salt concentration
Authors: Joanne M. Donovan, Audrey A. Jackson
Journal: Hepatology (1998)

The intermixed micellar/intervesicular bile salt (BS) concentration (IMC), composed of BS monomers and simple micelles, is in dynamic equilibrium with mixed micelles and vesicles. Accurate separation of biliary lipid aggregates is believed to depend on accurately measuring the IMC. Using centrifugal ultrafiltration, we measured the IMC of cholesterol-supersaturated model biles that were physiologically composed. Gel chromatography was performed using eluants containing the following: 1) the IMC; 2) the same BS composition as the IMC but higher or lower BS concentrations; 3) the same BS concentration as the IMC, but with more hydrophilic or hydrophobic BS; and 4) 10 mmol/L cholate. Compared with an eluant containing the same BS composition as the IMC, an eluant containing the same relative BS composition but 75% of the IMC increased the proportion of cholesterol in vesicles and decreased the vesicular cholesterol/egg yolk phosphatidylcholine (EYPC) ratio. In contrast, an eluant containing 150% of the IMC entirely transformed vesicles to micelles. Eluants containing slightly more hydrophobic or more hydrophilic BS eliminated or increased vesicular cholesterol content, respectively. An eluant of 10 mmol/L cholate overestimated vesicular cholesterol and in concentrated biles reproducibly produced an incompletely separated intermediate peak, possibly because of re-equilibration between mixed micelles and vesicles. Further, in concentrated biles, fractions eluting at volumes corresponding to mixed micelles were visibly turbid, irrespective of the eluant used. The correct IMC allows accurate separation of biliary lipid aggregates, but differences in BS concentration or composition substantially alter the vesicular percentage of cholesterol as well as the cholesterol/EYPC ratio. Elution with 10 mmol/L cholate may introduce artifactual gel-filtration peaks and inadequate separation of particles with widely differing molecular weights, both of which have confused previous analyses of biliary lipid aggregates.
Evaluation of GHb Assays in France by National Quality Control Surveys
Authors: Philippe Gillery, Gilles Dumont, Anne Vassault
Journal: Diabetes Care (1998)

To evaluate the state of the art concerning GHb assays through analysis of a large-scale quality control survey and to compare the results with those of previous surveys.A lyophilized hemolyzate prepared from human erythrocytes containing a physiological HbA1c level (5.5%) was sent to 3,500 French laboratories in February of 1995 and assayed as a patient's sample under routine conditions. Distribution of values was analyzed from the reported results for each method. The results were compared with the assigned value (acceptable range: +/- 20%) and with the upper value of the reference range currently used.Results were obtained from 2,674 laboratories, among which 39% used cation-exchange chromatography methods, 37.5% affinity chromatography, 16% immunological methods, and 7.5% electrophoresis. The number of laboratories using immunological methods increased from 100 to 400 between 1993 and 1995. The overall interlaboratory coefficient of variation (CV) was 20.2%, with within-method CVs ranging between 3.2 and 29.5%. Method-to-method accuracy varied dramatically, with mean HbA1c values ranging from 4.4 to 8.2%. Results from 75% of the laboratories were comprised in the acceptable range; 88% of them reported a value within the normal range of the method used.The interlaboratory variability of results illustrates the difficulties encountered by diabetologists in the follow-up of diabetic patients using results obtained from different laboratories. It demonstrates the usefulness of the internationally developed standardization process of GHb measurements and points out the need for laboratories to fulfill good practices.
The Association between Environmental Lead Exposure and Bone Density in Children
Authors: James R. Campbell, Randy N. Rosier, Leonore Novotny, J. Edward Puzas
Journal: Environmental Health Perspectives (2004)

Osteoporosis is a decrease in bone mineral density (BMD) that predisposes individuals to fractures. Although an elderly affliction, a predisposition may develop during adolescence if a sufficient peak BMD is not achieved. Rat studies have found that lead exposure is associated with decreased BMD. However, human studies are limited. We hypothesized that the BMD of children with high lead exposure would be lower than the BMD of children with low lead exposure. We collected data on 35 subjects; 16 had low cumulative lead exposure (mean, 6.5 microg/dL), and 19 had high exposure (mean, 23.6 micro g/dL). All were African American; there was no difference between the groups by sex, age, body mass index, socioeconomic status, physical activity, or calcium intake. Significant differences in BMD between low and high cumulative lead exposure were noted in the head (1.589 vs. 1.721 g/cm2), third lumbar vertebra (0.761 vs. 0.819 g/cm2), and fourth lumbar vertebra (0.712 vs. 0.789 g/cm2). Contrary to our hypothesis, subjects with high lead exposure had a significantly higher BMD than did subjects with low lead exposure. This may reflect a true phenomenon because lead exposure has been reported to accelerate bony maturation by inhibiting the effects of parathyroid hormone-related peptide. Accelerated maturation of bone may ultimately result in a lower peak BMD being achieved in young adulthood, thus predisposing to osteoporosis in later life. Future studies need to investigate this proposed model.
GPs in England must report certain patient harms under new rules
Authors: C. Dyer
Journal: BMJ (2015)

GPs and private healthcare providers in England are under a new legal duty from 1 April to tell patients if something goes wrong with their care and they experience specific types of harm.

The statutory duty of candour, which has applied to NHS hospital trusts since last November, has been extended to primary care and the independent sector.1

Doctors are already under an ethical duty, as spelt …
Social deprivation and premature mortality: regional comparison across England.
Authors: M Eames, Y Ben-Shlomo, M G Marmot
Journal: BMJ (1993)

OBJECTIVE--To investigate the pattern and size of the relationship between social deprivation in electoral wards and premature mortality for each health region in England. DESIGN--Ecological study using 1981 census variables and data on mortality for 1981-5. SETTING--14 regional health authorities in England. MAIN OUTCOME MEASURE--Mortality under the age of 65 years from all causes, coronary heart disease, and smoking related diseases in men and women. RESULTS--Increasing deprivation was significantly associated with mortality from all causes, coronary heart disease, and smoking related diseases. The relationship was linear with no apparent threshold. Correlation coefficients were generally greater for deaths from all causes and smoking related diseases and for men compared with women. The slope of the relationship between deprivation and mortality varied among regions. Variations in mortality still existed between regions for equal levels of deprivation. CONCLUSION--Deprivation of an area and premature mortality are strongly linked. The effects of deprivation can be seen throughout the range of affluence and are not limited to the poorest areas. Current targets for reducing coronary heart disease mortality may be achievable if the mortality in poor areas can be reduced to the rates in affluent areas.
Mast cell mediator release as a function of cyclic AMP-dependent protein kinase activation.
Authors: C M Winslow, R A Lewis, K F Austen
Journal: The Journal of Experimental Medicine (1981)

Stereo-specific perturbation of the IgE-receptor (shown in previous studies) produces a monophasic rise in cyclic AMP that peaks at 15 s and a depletion of cyclic AMP-dependent protein kinase that plateaus at 30-60 s. The previously observed linear relationship between the attenuation in the monophasic rise in cyclic AMP and the quantity of mediator release in the presence of incremental concentrations of the adenosine analogue 2',5',-dideoxyadenosine, DDA, which is known to inhibit adenylate cyclase, indicated a direct relationship between receptor perturbation, transmembrane activation of adenylate cyclase, and granule secretion. The role of cyclic AMP as a second messenger in this sequence is now apparent from the linear relationship between net percent mediator release and net percent activation of cyclic AMP-dependent protein kinase isoenzyme when IgE-dependent activation of adenylate cyclase is suppressed by incremental quantities of DDA. There was a comparable percent activation of both types I and II mast cell cyclic AMP-dependent protein kinase isoenzymes with anti-IgE-induced activation and secretion, and there was a parallel suppression of the activation of both isoenzymes in the presence of DDA. Although these studies firmly link the activation of cytoplasmic cyclic AMP-dependent protein kinase to the IgE receptor-initiated transmembrane activation of adenylate cyclase. they do not discriminate among the functions of the two isoenzymes.
Risk Assessment in Patients with Acute Myeloid Leukemia and a Normal Karyotype
Authors: Marianne Bienz, Madleina Ludwig, Beatrice U. Mueller, Elisabeth Oppliger Leibundgut, Daniel Ratschiller, Max Solenthaler, Martin F. Fey, Thomas Pabst
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The recognition of a number of leukemia-specific cytogenetic abnormalities and their role as independent prognostic factors have provided considerable insights into leukemia pathogenesis and have paved the way to adopt risk-adapted treatment. However, ∼50% of newly diagnosed acute myeloid leukemia (AML) have a normal karyotype. There has therefore been much interest in identifying molecular markers that could help to improve the prognostic stratification of patients with normal-karyotype AML. Experimental Design: Consecutive untreated AML patients (n = 67) from a single institution all with normal karyotype were analyzed for the presence of mutations in the myeloid transcription factor gene CEBPA (for CCAAT/enhancer binding protein-α), for internal tandem duplications (ITD) of the tyrosine kinase receptor gene FLT3 (for fms-like tyrosine kinase 3), and for expression of the BAALC gene (for brain and acute leukemia, cytoplasmic). Results: 17.9% of normal-karyotype AML had mutations in the CEBPA gene, and 28.4% had FLT3-ITD; 65.7% (44 of 67) had high BAALC expression and 34.3% (23 of 67) had low BAALC expression. Patients with CEBPA mutations had a very favorable course of their disease. Median disease-free survival (DFS) and overall survival (OS) were 33.5 and 45.5 months, respectively, compared with 10 (e.g., 12 months in patients without CEBPA mutations; P = 0.0017; P = 0.0007). AML patients with FLT3-ITD had significantly shorter median DFS (P = 0.0328) and OS (P = 0.0148) than patients without FLT3-ITD. High BAALC expression predicted for a shorter DFS (P = 0.0152) and OS (P = 0.0210) compared with AML with low BAALC expression; 53.7% of normal-karyotype AML had neither FLT3-ITD nor CEBPA mutations. We found that high BAALC expression in normal-karyotype AML with neither FLT3-ITD nor CEBPA mutations (18 of 67) indicates adverse prognosis for both DFS and OS (P = 0.0001; e.g., P = 0.0001) compared with the group with low BAALC expression and absent FLT3-ITD and CEBPA mutations (18 of 67). Thus, BAALC expression represents a novel prognostic marker particularly for normal-karyotype AML patients with neither FLT3-ITD nor CEBPA mutations. Conclusions: Assessment of CEBPA mutations, FLT3-ITD, and BAALC expression permits to split normal-karyotype AML into clinically distinct subgroups.
Endoscopy of the Biliary Tract and the Pancreas in Children
Authors: J. Riemann, H. Koch
Journal: Endoscopy (1978)

ERCP is a useful method in adults for diagnosing bilio-pancreatic disorders. The application of this technique in children is limited until now according to the rare case reports in the literature. Our experience with this procedure, based on the examination of six children and 12 youths, shows that ERCP can be employed with great benefit, when taking into account the correct indication. ERCP is mainly applied to clarify obstructive jaundice, especially when anomalies of the bile duct system are suspected, and to discover a reason for relapsing pancreatitis where other procedures fail. Blunt abdominal traumata with upper GI bleeding may well be another reason. In general our first reported data are encouraging.
Evaluating the Cost-Effectiveness of Counselling in Health Care
Authors: T. Sensky
Journal: BMJ (1996)

Keith Tolley, Nancy Rowland Routledge, pounds sterling14.99, pp 210 ISBN 0 415 07661 7

Recent years have seen increasing demands for counselling, particularly in general practice settings. Having access to a counsellor usually proves popular with patients, and is often supported by their doctors. Some general practice fundholders have even chosen to purchase counselling at the expense of other resources such as community psychiatric nursing. Can this be justified as an effective use of resources? Similarly, some cardiology services incorporate counselling into their rehabilitation programmes, while others do not. What is the evidence in this setting that counselling can be cost effective?

Although Evaluating the …
Oral Thyroxine: Variation in Biologic Action and Tablet Content
Authors: CLARK T. SAWIN
Journal: Annals of Internal Medicine (1984)

Thirty-two patients with primary hypothyroidism were given oral thyroxine as Levothroid or Synthroid to see if the two preparations had similar effects. The serum thyroxine was used as an index of bioavailability and the serum thyrotrophin as an index of biologic activity. The serum thyroxine was lower in all 32 patients when taking Synthroid than when taking Levothroid. In 15 patients the serum thyroxine level fell low enough to raise the serum thyrotrophin; in all 15 the serum thyrotrophin rose when taking Synthroid. Direct measurement of thyroxine in the tablets showed that the tablets of Synthroid contained 20% to 30% less thyroxine than their stated content. Thus, the decreased bioavailability (lower serum thyroxine) and decreased biologic action (higher serum thyrotrophin) of Synthroid were due to the lower content of thyroxine. An incidental observation is that the range of serum thyroxine in treated hypothyroid patients is 7.6 to 16.6 µg/dL, higher than in normal persons. Because oral thyroxine is widely used, a cooperative effort among manufacturers, the United States Pharmacopeia and Food and Drug Administration, and clinicians to ensure the potency and biologic action of oral thyroxine is in order. Meanwhile, it seems reasonable to use oral thyroxine that is close to the stated content.
Content without a frame? The role of vocabulary biases in speech errors
Authors: Trevor A. Harley
Journal: Behavioral and Brain Sciences (1998)

Constraints on the types of speech errors observed can be accounted for by a frame/content distinction, but connectionist modeling shows that they do not require this distinction. The constraints may arise instead from the statistical properties of our language, in particular, the sequential biases observed in the vocabulary. Nevertheless, there might still be a role for the frame/content distinction in syntactic planning.
Nocturnal Cortisol Release During Hypoglycemia in Diabetes
Authors: R S Scott, M S Scandrett
Journal: Diabetes Care (1981)

Nocturnal hypoglycemia in insulin-treated diabetic persons is often difficult to recognize clinically. It has been suggested that a useful biochemical test to demonstrate this would be the increased excretion of cortisol in the urine during the overnight period. However, of six diabetic persons who had nocturnal hypoglycemia (≤2.5 mmol/L), plasma cortisol profiles and overnight urinary cortisol-creatinine ratios were abnormal in only one. In four others the plasma cortisol levels and cortisol excretion indices were indistinguishable from either a normal control group or a group of five diabetic subjects who did not develop nocturnal hypoglycemia. The remaining patient had a raised urinary cortisol-creatinine ratio, but did not show increased plasma levels of cortisol, growth hormone, or glucagon during the hypoglycemic phase. These data do not support the usefulness of the urinary cortisol-creatinine index as a marker of nocturnal hypoglycemia in diabetes.
FDA rules that researchers will have to disclose financial interest
Authors: D. Josefson
Journal: BMJ (1998)

Drug companies submitting licensing applications to the Food and Drug Administration (FDA) in the United States will now have to reveal whether researchers involved in a drug trial have any financial interest in the company. The new regulations aim to eliminate possible data bias arising from financial considerations.

Effective from February 1999, the new rules will require companies to disclose whether clinical investigators have received stock and patent options, payments in the form of research grants, gifts of equipment, consultant fees, and honorariums from lectures.

Drug companies routinely recruit doctors and scientists to study their products and to conduct clinical …