tbuckley/cabot-search huggingface dataset:
Help for the child who is sexually abused.
Authors: M Duddle
Journal: BMJ (1984)

oxygen-selects this over the systemic circulation; so they may produce systemic hypotension, and this has indeed been a problem with hydralazine in several studies.'2 13 The calcium antagonist nifedipine is able to block hypoxic vasoconstriction in the pulmonary circulation. 14Both nifedipine and hydralazine have shown beneficial haemo- dynamic effects on secondary pulmonary hypertension in acute and short term studies in some hands. 13-18The consensus is that when these drugs are first used their effects should be monitored by invasive haemodynamic measurements to con- firm effectiveness and help cope with adverse effects.Unfortunately, the changes in pulmonary artery pressure after eight weeks of treatment are not always predictable from the initial changes.II Vasodilators which also act on the venous side, such as nitroglycerin (glyceryl trinitrate) and nitroprusside, may be harmful.,,The right ventricle probably needs a good filling pressure to keep up its adaptive response with a high cardiac output.Similarly, overenthusiastic use of diuretics may be harmful.It is worth tolerating a little oedema to give the heart a good head of steam.Digoxin, which might be expected to have a further positive inotropic effect, is not useful in cor pulmonale unless there is coexistent atrial fibrillation. 19 Haemodynamic benefits at rest and on exercise have been shown from oral or parenteral V stimulants,20-26 with little apparent difference from the choice among the selective agents.26The action is thought to be a combination of positive inotropic effect and pulmonary vasodilatation.24Haemo- dynamic effects have continued for six weeks with no problems except in patients with pre-existing extrasystoles.24Invasive monitoring is not necessary; a response may be con- firmed by radionuclide measurements ofthe ejection fraction, though this presents difficulties in the presence of over- inflation.Carefully controlled long term studies will be necessary, however, before ,B stimulation can be regarded as routine treatment for cor pulmonale.Possibly a further increase in cardiac output maintained over many months might even be deleterious.Perhaps the V stimulant responses give a clue to the future; what is needed may be a combined approach, improving oxygen carriage by giving oxygen or almitrine while dropping the pulmonary artery pressure with selective vasodilators and improving cardiac output with an inotrope.At present, however, treatment should be to get the patient to stop smoking, reverse his airflow obstruction, go easy on the diuretics, and then consider long term low flow oxygen or possibly an oral Pi stimulant.Meanwhile, clinicians should wait for a selective pulmonary vasodilator, more data on almitrine, and, most important, trials to show that early changes in haemodynamics continue and produce long term clinical improvement-and reduce mortality.
Private Medical Practice and the National Health Service
Authors: John Lister
Journal: New England Journal of Medicine (1984)

The essence of private medical practice lies in the nature of the relationship between patients and their physicians. In its most simple form this relationship is characterized by patients' making their own choice of doctors, establishing a direct contract with them, and being responsible for meeting their professional fees and other medical or surgical expenses.The intervention of a third party, in the form either of some type of national health service or of an insurance carrier, has modified the relationship so that the distinction between public and private patients is less clear than before.However, as Iglehart1 , 2 has pointed . . .
Newborn Intensive Care and Neonatal Mortality in Low-Birth-Weight Infants
Authors: Nigel Paneth, John L. Kiely, Sylvan Wallenstein, Michele Marcus, Jean Pakter, Mervyn Susser
Journal: New England Journal of Medicine (1982)

We examined the neonatal mortality rates of low-birth-weight infants (501 to 2250 g) born between 1976 and 1978 in three kinds of hospitals in New York City: those with newborn-intensive-care units (Level 3), those with capabilities for the care of most premature infants (Level 2), and those without any special facilities for premature newborns (Level 1). Among 13,560 singleton low-birth-weight infants, the adjusted neonatal mortality rate for Level 3 hospitals was 128.5 per thousand live births - significantly lower (P less than 0.001) than the rates for both level 2 (168.1) and Level 1 units (163.0). The association of level of care with mortality could not be accounted for by differences between groups in social or demographic status, in prenatal care, or in medical complication of pregnancy. We infer that birth at a Level 3 center lowers neonatal mortality in low-birth-weight infants. However, only 34 per cent of the patients in this study were born in such units.
Methodologic and statistical approaches to studying human fertility and environmental exposure.
Authors: Candace Tingen, Joseph B Stanford, David B Dunson
Journal: Environmental Health Perspectives (2003)

Although there has been growing concern about the effects of environmental exposures on human fertility, standard epidemiologic study designs may not collect sufficient data to identify subtle effects while properly adjusting for confounding. In particular, results from conventional time to pregnancy studies can be driven by the many sources of bias inherent in these studies. By prospectively collecting detailed records of menstrual bleeding, occurrences of intercourse, and a marker of ovulation day in each menstrual cycle, precise information on exposure effects can be obtained, adjusting for many of the primary sources of bias. This article provides an overview of the different types of study designs, focusing on the data required, the practical advantages and disadvantages of each design, and the statistical methods required to take full advantage of the available data. We conclude that detailed prospective studies allowing inferences on day-specific probabilities of conception should be considered as the gold standard for studying the effects of environmental exposures on fertility.
Effects of Left Ventricular Assist Device Support on Biomarkers of Cardiovascular Stress, Fibrosis, Fluid Homeostasis, Inflammation, and Renal Injury
Authors: Tariq Ahmad, Teresa Wang, Emily C. O'Brien, Marc D. Samsky, John A. Pura, Yuliya Lokhnygina, Joseph G. Rogers, Adrian F. Hernandez, Damian Craig, Dawn E. Bowles, Carmelo A. Milano, Svati H. Shah, James L. Januzzi, G. Michael Felker, Chetan B. Patel
Journal: JACC Heart Failure (2014)
Abstract 5634: Increased co-amplification of HER2 and STARD3 in a cell line model of acquired lapatinib resistance.
Authors: Martina McDermott, Lee Anderson, Liam Shields, Neil O'Brien, Allison Prendergast, Susan Kennedy, William Gallagher, Radoslaw Zagozdzon, Annette Byrne, John Crown, Dennis Slamon, Norma O'Donovan
Journal: Cancer Research (2013)

Abstract Resistance to lapatinib, a tyrosine kinase inhibitor of HER2, is a significant clinical problem and to date the mechanisms of acquired lapatinib resistance remain largely unknown. In order to study acquired lapatinib resistance we established an in vitro cell line model through continuous culture of HCC1954 cells with 1 μM lapatinib. After 6 months the resulting HCC1954-L cells where significantly less sensitive to lapatinib with an IC50 of 2.6 ± 0.3 μM compared to aged-matched parental cells (IC50 0.42 ± 0.02 M; p = 0.004). In addition, lapatinib treatment had no significant effect on the growth of HCC1954-L xenograft tumors in mice, indicating the utility of HCC1954-L cells as an in vivo model of acquired lapatinib resistance. Array CGH analysis was performed on the sensitive and resistant cell lines. Chromosomal aberrations were detected in 15 regions in the HCC1954-L cells, including increased amplification of the region of chr17q12 known to contain HER2 and STARD3. Immunoblotting was performed to assess whether the increased amplification corresponded with increased expression of the proteins. HCC1954-L cells exhibited a small but significant increase (1.2 fold) in HER2 protein expression (p=0.02) compared to parental cells. Increased gene amplification of HER2 was also confirmed by FISH analysis. While STARD3 protein expression was undetectable in in parental HCC1954 cells, HCC1954-L cells expressed high levels of STARD3 protein. Knockdown of STARD3 using siRNA resulted in a 20% decrease in cell growth compared to scrambled control treated cells, suggesting that STARD3 amplification and expression plays a role in the proliferation of HCC1954-L cells. In summary, we have developed a robust model of acquired lapatinib resistance which exhibits increased amplification and expression of HER2 and STARD3. Citation Format: Martina McDermott, Lee Anderson, Liam Shields, Neil O'Brien, Allison Prendergast, Susan Kennedy, William Gallagher, Radoslaw Zagozdzon, Annette Byrne, John Crown, Dennis Slamon, Norma O'Donovan. Increased co-amplification of HER2 and STARD3 in a cell line model of acquired lapatinib resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5634. doi:10.1158/1538-7445.AM2013-5634
Gambogic acid, a novel ligand for transferrin receptor, potentiates TNF-induced apoptosis through modulation of the nuclear factor-κB signaling pathway
Authors: Manoj K. Pandey, Bokyung Sung, Kwang Seok Ahn, Ajaikumar B. Kunnumakkara, Madan M. Chaturvedi, Bharat B. Aggarwal
Journal: Blood (2007)
Galactorrhoea: Successful Treatment with Reduction of Plasma Prolactin Levels by Brom-ergocryptine
Authors: G. M. Besser, L. Parke, C. R. W. Edwards, I. A. Forsyth, A. S. McNeilly
Journal: BMJ (1972)

In five patients with inappropriate lactation and amenorrhoea or impotence brom-ergocryptine was found to suppress the lactation and to diminish the raised plasma prolactin levels. The responses to treatment suggest that there may be an inverse relationship between prolactin secretion and gonadotrophin secretion in man.
Immunologic Aspects of Endocrine Diseases
Authors: Jordan N. Fink
Journal: JAMA (1982)

ENDOCRINE organs, with their highly specialized functions, contain organ-specific tissue antigens capable of inducing autoimmune responses under appropriate conditions. Some of the endocrine diseases with autoimmune phenomena are listed in Table 13-1. Immunologic aspects of the diseases listed in this table are discussed in this chapter. <h3>THYROID DISEASES</h3><h3>Hashimoto's Thyroiditis</h3> Hashimoto's or autoimmune thyroiditis is a common disease. The incidence, now 1% to 2% at autopsy, appears to be increasing. The incidence increases with age, is four times more common in women than men, and four times more common in white than black persons. There may be familial aggregations of the disease, although this tendency is not so marked as with Graves' disease. To date, there is no conclusive evidence of any association with HLA or bloodgroup antigens. <h3>Pathology</h3> In the thyroid gland there are variable degrees of depletion of colloid from the follicles, Askenazy's cellchange, infiltration with lymphocytes, germinal-center
Intestinal Spirochaetosis of the Colon Diagnosed with Colono-ileoscopy and Multiple Biopsies
Authors: R. Willén, B. Carlén, J. Cronstedt, H. Willén
Journal: Endoscopy (1985)

This paper deals with the clinical history, the histopathological and TEM features of a case of intestinal spirochaetosis associated with ulcerative colitis and tubular adenomas of the colon. It is the fifth described case of intestinal spirochaetosis in Sweden, and the first in the literature in which a complete colonoscopy with multiple biopsies has been performed. Intestinal spirochaetosis might lead to minor complaints as distension and vague abdominal discomfort, as in this case, but also to more prominent symptoms such as diarrhoea. Heavy infestation of the gut surface epithelium by spirochaetes was seen in the total colon, but was not found in the distal ileum.
Relationship Between First-Phase Insulin Secretion and Age, HLA, Islet Cell Antibody Status, and Development of Type I Diabetes in 220 Juvenile First-Degree Relatives of Diabetic Patients
Authors: Jean-J Robert, Ingeborg Deschamps, Didier Chevenne, Marc Roger, Agnès Mogenet, Christian Boitard
Journal: Diabetes Care (1991)

Objective To assess the adequacy of the first-phase insulin response for predicting development of insulin-dependent diabetes. Research Design and Methods Determinations were made of 1- and 3-min insulin responses to glucose (0.5 g/kg i.v.), islet cell antibodies (ICAs), insulin autoantibodies (IAAs), and HLA. We studied 220 first-degree relatives (aged 3–29 yr) of diabetic patients; 75 underwent two or more tests. Results At the first test, insulin responses correlated with age in ICA− children ≤ 11 yr old (r = 0.46, P &amp;lt; 0.001). Individual responses varied widely in all ages, and low values were common (5th percentile: 108 pM in children &amp;lt; 5 yr old, 180 pM thereafter). No correlation was found between insulin responses and IAAs or HLA. The responses of 15 ICA+ subjects were not significantly different from those of ICA− subjects after excluding the influence of age. At subsequent tests, ICA+ and ICA− subjects displayed distinct changes; the mean ± SE insulin response increased in ICA− subjects from 619.2 ± 40.8 to 716.4 ± 50.4 pM (P &amp;lt; 0.001) but declined in ICA+ subjects from 403.2 ± 91.8 to 313.8 ± 67.2 pM (P &amp;lt; 0.02). During follow-up, 5 of 9 (56%) consistently ICA+ siblings developed diabetes or impaired glucose tolerance compared with 1 of 54 (2%) consistently ICA− subjects. The sensitivity and specificity of two or more low insulin responses (300 pM) for predicting progression to diabetes were 60 and 96%, respectively; the predictive value was 43%. The highest predictive value (75%) was achieved by the combination consistently ICA+, consistently low insulin response, and HLA-DR3/4. However, in no subject could the time of onset of diabetes be deduced from the decline of the insulin response. Conclusions Consecutive intravenous glucose tolerance tests are a useful complement for predicting progression to diabetes but not its onset.
Neutrophil activation in paediatric extracorporeal circuits: effect of circulation and temperature variation
Authors: M. H El Habbal, H. Carter, L. J Smith, M. J Elliott, S. Strobel
Journal: Cardiovascular Research (1995)

Upregulation of neutrophil adhesion molecules (CD11b and L-selectin) and release of a modulating cytokine (IL8) have been reported in vivo and in vitro in adult cardiopulmonary bypass. The aim of this study was to determine whether paediatric bypass preparations have similar influences and whether neutrophil-endothelium interactions are required for IL8 release.In vitro paediatric cardiopulmonary bypass circuits (n = 15) were constructed (identical to those used clinically), as well as static loops (n = 15) using donor blood. The effects of circulation and temperature (17 degrees C, 25 degrees C, 37 degrees C) on the initiation of acute inflammation were examined. Cellular expressions of neutrophil adhesion molecules CD11b and L-selectin were assayed by immunofluorescence technique, and serum IL8, IL6, TNF-alpha, leucocyte elastase, and terminal complement complex were measured by ELISA.In all experiments, an immediate increase in CD11b expression occurred [median values, in relative fluorescence units: 64.9 (range 45.3-212.9) at rest; 365.2 (205-835.4) at 10 min; P < 0.001], along with a decrease in L-selectin expression [153.5 (115.5-220.7) at rest; 42 (12-134) at 10 min; P < 0.01]. Serum concentrations of the following increased gradually and were higher in circulation than in static loops: IL8 [1500 (500-2500) pg.ml-1 in circuit v 600 (180-1500) pg.ml-1 in loop, P < 0.001]; TNF-alpha P < 0.05]; and terminal complement complex [25.9 (6.8-120) v 4.7 (0-21.6) AU.ml-1, P < 0.01]. Cooling decreased and rewarming increased upregulation of CD11b and downregulation of L-selectin and release of IL8. IL6 was undetectable.In the absence of endothelium, in vitro paediatric cardiopulmonary bypass causes profound acute inflammatory changes in donor blood with release of IL8. These changes were greater than in adult cardiopulmonary bypass. Temperature variation and circulation modulate the responses.
Abstract 3986: Effects of immunohistochemistry on biomolecules in tissue specimens: Importance for expression-based microdissection technologies
Authors: Michael A. Tangrea, Matthew S. Kreitman, Alex M. Rosenberg, Eleanor C. Ory, Sumana Mukherjee, Franziska C. Eberle, Benjamin S. Wallis, Jeffrey C. Hanson, Jaime Rodriguez-Canales, Michael R. Emmert-Buck
Journal: Cancer Research (2010)

Abstract Immuno-Laser Capture Microdissection (LCM) and Expression Microdissection (xMD) are techniques that rely on immunohistochemistry (IHC) to specifically define target cells for microdissection. While these techniques have been successfully applied to LCM and xMD, the full effects of IHC on the biomolecules extracted from stained samples are not well characterized. The goal of our study was to evaluate the integrity of DNA, RNA and protein biomolecules obtained from tissue sections after standard IHC or immunofluorescence (IF) techniques. Utilizing snap frozen human prostate and ovarian carcinoma specimens, as well as mouse liver samples, we evaluated biomolecule recovery from immunostained samples, including histone and pan-cytokeratins AE1/AE3 targeted antibodies. Standard horseradish peroxidase and diaminobenzidine (DAB) based IHC was used as well as Alexa Fluor 488 for indirect-IF. In general, biomolecule recovery was diminished in IHC stained tissues compared to standard hematoxylin and eosin (H&amp;E) staining. RNA was affected the most and showed significantly reduced quantity and quality after staining. DNA was recoverable, but quantities were reduced when compared to the standard H&amp;E. However, PCR amplification was possible with all stained samples studied. Protein analysis also demonstrated a reduction of quantity of the proteins recovered from IHC stained samples, with a variable effect depending on the protein analysis methodology. The results demonstrated that IHC techniques using DAB labeling significantly affect the extracted biomolecules. Improved staining protocols are required to address these concerns and to further the capabilities of these potentially powerful microdissection techniques. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3986.
Charity warns of “daunting challenges” for Iraq health system
Authors: Owen Dyer
Journal: BMJ (2004)

Iraq's Ministry of Health faces “daunting challenges” in its effort to rebuild the country's shattered medical infrastructure, according to a report released this week by the health charity Medact. “Even if the circumstances were much more auspicious, the difficulty of reversing this downward spiral could not be underestimated,” suggests the report.

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Hala Madkoor, 24, injured by a roadside bomb in Iraq, is comforted by her brother at a Baghdad medical centre 

Credit: KARIM KADIN/AP

The report mostly avoids allocating blame for the cumulative damage wreaked by dictatorship, three wars, …

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Immunology in Ulcerative Colitis
Authors: Albert H. Rowe
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Because the editorial "The Immunological Aspects of Ulcerative Colitis" (<b>198</b>:659, 1966) failed to mention atopic allergy to food and pollens, we believe that the following comments deserve consideration. Food allergy as a cause of chronic ulcerative colitis (CUC) was first reported by Andresen in 1933,<sup>1</sup>and has been reported by us since 1942.<sup>3</sup>Pollen allergy as a sole etiological factor, or associated with food allergy, was also reported by us in 1942 and reemphasized in 1955.<sup>3</sup>We are convinced that when the causative food or pollen allergy is controlled by increasing numbers of physicians, atopic allergy will be recognized as a major cause of CUC. The causative role of atopic allergy was given support with the demonstration of gamma globulin antibodies to milk by Trueblood and Wright in 1961.<sup>4</sup>Although these antibodies are found in clinically non-milk-sensitive individuals, they occur more often
Health professionals from around world are urged to campaign on climate change
Authors: Z. Kmietowicz
Journal: BMJ (2009)

Doctors and other health professionals from around the world are being invited to join a new international campaigning group set up to lobby governments to take urgent action to protect health by limiting climate change.

Robin Stott, who co-chairs the UK Climate and Health Council and facilitates the organisation’s new international arm, said that the key message from health professionals to their institutions and governments is that “what’s good for the climate is good for health.”

The council believes that “tackling climate change and ending poverty are the two most important, urgent priorities to …
Impaired Skeletal Muscle Blood Flow Control With Advancing Age in Humans
Authors: Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno
Journal: Circulation Research (2012)

Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation.We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, both hypoxia and exercise significantly increased venous [ATP] and ATP effluent (forearm blood flow×[ATP]) draining the skeletal muscle. In contrast, hypoxia and exercise did not increase venous [ATP] in older adults, and both venous [ATP] and ATP effluent were substantially reduced compared with young people despite similar levels of deoxygenation. Next, we demonstrated that this could not be explained by augmented extracellular ATP hydrolysis in whole blood with age. Finally, we found that deoxygenation-mediated ATP release from isolated erythrocytes was essentially nonexistent in older adults.Skeletal muscle blood flow during conditions of erythrocyte deoxygenation was markedly reduced in aging humans, and reductions in plasma ATP and erythrocyte-mediated ATP release may be a novel mechanism underlying impaired vasodilation and oxygen delivery during hypoxemia with advancing age. Because aging is associated with elevated risk for ischemic cardiovascular disease and exercise intolerance, interventions that target erythrocyte-mediated ATP release may offer therapeutic potential.
Evidence for Involvement of Calcitonin Gene-Related Peptide in Nitroglycerin Response and Association With Mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) Glu504Lys Polymorphism
Authors: Ren Guo, Xiao-Ping Chen, Xin Guo, Lei Chen, Dai Li, Jun Peng, Yuan-Jian Li
Journal: Journal of the American College of Cardiology (2008)