tbuckley/cabot-search huggingface dataset:
Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene.
Authors: K Fujieda, T Tajima, J Nakae, S Sageshima, K Tachibana, S Suwa, T Sugawara, J F Strauss
Journal: Journal of Clinical Investigation (1997)

Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most severe form of CAH in which the synthesis of all gonadal and adrenal cortical steroids is markedly impaired. We report here the clinical, endocrinological, and molecular analyses of two unrelated Japanese kindreds of 46,XX subjects affected with lipoid CAH who manifested spontaneous puberty. Phenotypic female infants with 46,XX karyotypes were diagnosed with lipoid CAH as newborns based on a clinical history of failure to thrive, hyperpigmentation, hyponatremia, hyperkalemia, and low basal values of serum cortisol and urinary 17-hydroxycorticosteroid and 17-ketosteroid. These patients responded to treatment with glucocorticoid and 9alpha-fludrocortisone. Spontaneous thelarche occurred in association with increased serum estradiol levels at the age of 10 and 11 yr, respectively. Pubic hair developed at the age of 12 yr 11 mo in one subject and menarche was at the age of 12 yr in both cases. Both subjects reported periodic menstrual bleeding and subsequently developed polycystic ovaries. To investigate the molecular basis of the steroidogenic lesion in these patients, the StAR gene was characterized by PCR and direct DNA sequence analyses. DNA sequence analysis revealed that one patient is homozygous for the Gln 258 Stop mutation in exon 7 and that the other patient is a compound heterozygote with the Gln 258 Stop mutation and a single A deletion at codon 238 in the other allele causing a frame-shift, which renders the StAR protein nonfunctional. These findings demonstrate that ovarian steroidogenesis can be spared to some extent through puberty when the StAR gene product is inactive. This is in marked contrast to the early onset of severe defects in testicular and adrenocortical steroidogenesis which are characteristics of this disease.
P-selectin suppresses hepatic inflammation and fibrosis in mice by regulating interferon ? and the IL-13 decoy receptor
Authors: Thomas A. Wynn, Matthias Hesse, Netanya G. Sandler, Mallika Kaviratne, Karl F. Hoffmann, Monica G. Chiaramonte, Rachael Reiman, Allen W. Cheever, Joseph P. Sypek, Margaret M. Mentink-Kane
Journal: Hepatology (2004)

The selectin family of cell adhesion molecules is widely thought to promote inflammatory reactions by facilitating leukocyte recruitment. However, it was unexpectedly found that mice with targeted deletion of the P-selectin gene (PsKO mice) developed unpolarized type 1/type 2 cytokine responses and severely aggravated liver pathology following infection with the type 2-promoting pathogen Schistosoma mansoni. In fact, liver fibrosis, which is dependent on interleukin 13 (IL-13), increased by a factor of more than 6, despite simultaneous induction of the antifibrotic cytokine interferon gamma (IFN-gamma). Inflammation, as measured by granuloma size, also increased significantly in the absence of P-selectin. When infected PsKO mice were treated with neutralizing anti-IFN-gamma monoclonal antibodies, however, granuloma size was restored to wild-type levels; this finding revealed the potent proinflammatory role of IFN-gamma when expressed concomitantly with IL-13. Untreated PsKO mice also exhibited a significant (sixfold) reduction in decoy IL-13 receptor (IL-13 receptor alpha-2) expression when compared with infected wild-type animals. It is noteworthy, however, that when decoy receptor activity was restored in PsKO mice by treatment with soluble IL-13 receptor alpha-2-Fc, the exacerbated fibrotic response was completely inhibited. Thus, reduced expression of the decoy IL-13 receptor mediated by the elevated type 1 cytokine response probably accounts for the enhanced activity of IL-13 in PsKO mice and for the resultant increase in collagen deposition. In conclusion, the current study has revealed the critical role of P-selectin in the progression of chronic liver disease caused by schistosome parasites. By suppressing IFN-gamma and up-regulating the decoy IL-13 receptor, P-selectin dramatically inhibits the pathologic tissue remodeling that results from chronic type 2 cytokine-mediated inflammation.
A Classification of Schizophrenic Children Under Five Years
Authors: BARBARA FISH, THEODORE SHAPIRO, MAGDA CAMPBELL, RENEE WILE
Journal: American Journal of Psychiatry (1968)

Previous studies have demonstrated that severity of language impairment at five years of age is a critical determinant of long-term outcome for young schizophrenic children. Degrees of language impairment were therefore used as the major criteria for this prognostic classification of two-to five-year-old psychotic children. The classification discriminated patients with high and low probabilities of success with drugs and other treatments. it appears that it is also an indicator of long-term prognosis.
What If Americans Ate Less Fat?
Authors: Liarme Sheppard
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The article "What If Americans Ate Less Fat?" by Browner et al<sup>1</sup>addressed an interesting and important topic. However, the authors may have substantially underestimated the reductions in mortality rates that may follow a reduction in fat intakes to 30% of energy by overlooking the effects of random error in serum cholesterol measurement, and especially in dietary fat measurement, in projecting corresponding CHD and cancer RR estimates. Specifically, their CHD RR estimates (Table 1, p3287) for a 20 mg/dL increase in serum cholesterol levels used data from Multiple Risk Factor Intervention Trial screenees. The random measurement error associated with a single serum cholesterol measurement is such that corresponding log RR estimates are likely to be underestimated by a factor of about 1.5 (Richard Peto, Oxford University, oral communication, June 1986). This correction increases the projected impact of fat reduction on CHD mortality by more than 50%.
Marfan's Syndrome
Authors: J. Bingle
Journal: BMJ (1957)

BRDIBTNAL 629 ResultsThe tablet test could regularly detect a protein concentration of 0.005 g. per 100 ml. of urine: at 0.0025 g. per 100 ml.detection of proteinuria was inconstant.It was equally sensitive to the different proteins tested, and throughout the pH and specific gravity ranges which were examined.The tablets appeared to be.stable, and tablets which had been stored at room temperature for three months were as effective as at the time the bottle of tablets was first opened.The solution test was also sensitive to 0.005 g. per 100 ml. and usually to 0.0025 g. per 100 ml., and the boiling test was regularly sensitive to 0.0025 g. per 100 ml.while inconstant results were obtained at 0.001 g. per 100 ml.; both these tests were also unaffected by the nature of the protein and the pH or specific gravity of the urine.The ingenious internal indicator of the tablet test enables successful correction of the pH of alkaline urines.The
Sildenafil (Viagra) is used as a recreational drug in England
Authors: J. Aldridge, F. Measham
Journal: BMJ (1999)

Carriage of meningococci in contacts of patients with meningococcal disease"Kissing contacts" need to be defined Editor-In their study Kristiansen et al show high carriage rates of pathogenic strains of Neisseria menigitidis in household and kissing contacts of patients with invasive meningococcal disease. 1 While it is easy to define a household contact it may be more difficult to define a kissing contact.There are many types of kiss, ranging from a "peck on the cheek" to much more!In some cultures kissing is as common as shaking hands.In such situations widespread chemoprophylaxis to "kissing contacts" may not be appropriate.It would be valuable to know whether Kristiansen et al placed any restrictions on who was defined as a kissing contact.
GPs need better incentives to reduce health inequalities, says audit office
Authors: J. Carlowe
Journal: BMJ (2010)

The Department of Health for England is on course to miss a Public Service Agreement target set in 2002 to reduce health inequalities by 10% by 2010 as the gap between the richest and the poorest widens, an audit has found.

The latest report from the National Audit Office found that because the department was slow to set up initiatives to tackle inequality, with most implemented in the mid 2000s, it was impossible to determine if its approach provided value for money, although it did think this “likely.”

Moreover, although life expectancy overall had increased, the gap in life expectancy between the national average and the government’s dedicated “spearhead areas” (72 local authorities in the bottom …
Functional Significance of Hemodynamic Overload–Induced Expression of Leukemia-Inhibitory Factor in the Adult Mammalian Heart
Authors: Feng Wang, Yukihiro Seta, Georg Baumgarten, David J. Engel, Natarajan Sivasubramanian, Douglas L. Mann
Journal: Circulation (2001)

Background —Leukemia-inhibitory factor (LIF) is a member of the interleukin-6 family of cytokines that utilize gp130 as a common signaling component. In the present study, we examined the mechanisms that govern LIF expression and functional effects in the adult heart. Methods and Results —LIF mRNA and protein biosynthesis were examined in the adult feline heart after hemodynamic overloading ex vivo. Both LIF mRNA and protein expression were detected within 60 to 90 minutes after hemodynamic overloading. Studies in isolated adult cardiac myocytes showed that these cells synthesized both LIF mRNA and protein. The functional effects of LIF in the heart were demonstrated by studies that showed that LIF stimulation led to a significant increase in general protein synthesis and an increase in sarcomeric protein synthesis. Pretreatment with LIF also protected the cells against hypoxia/reoxygenation-induced cardiac myocyte apoptosis and cellular injury. Finally, LIF had no effect on isolated cardiac myocyte cell motion. Conclusions —Hemodynamic overload is a sufficient stimulus for LIF expression in the adult mammalian heart. Given that LIF confers both hypertrophic and cytoprotective responses in adult cardiac myocytes, this study suggests that the expression of LIF within the heart may play an important role in mediating homeostatic responses within the myocardium.
Smallpox Vaccine in Plastic Tubing
Authors: M. H. F. Coigley
Journal: BMJ (1966)

polythene examination gloves.If wished, the thermometer could be wiped with spirit after removal of the sheath, but suitable trials might well prove this to be unnecessary.The cost of manufacture of such sheaths on a large scale should be very small, as I can make fifty in ten minutes by hand from a pennyworth of polythene.Perhaps, as the Ministry are prepared to supply disposable syringes in the cause of preventing crossinfection, they might be interested in these very much cheaper aids to the same cause.-I am, etc., London W.10. P. L. HOLMAN.SIR,-As a general practitioner I was in- terested to read the article by Drs.R. J. House and R. J. Henderson on the disinfect- ing of the clinical thermometer (11
GOVERNMENT RESPONSIBILITY TO THE STUDENT
Authors: J. H. Carstens
Journal: JAMA (1918)

<h3>To the Editor:</h3> —The government has taken over the military control of the medical schools, enlisted the students, and has agreed to pay their tuition fee, their board, and $30 a month. I understand that now that peace is in view the government is going to give this up, which is all right, but the students expect to have this year's teachings under the above terms, and now are not prepared to suddenly pay the expense for the balance of the term. So it seems to me that the government, even if it gives up the military control of all schools ought to carry out at least the financial agreement with the students until the end of the year. Not to do this would be a great injustice to some of the poorer students.
Muscular work and the release of prostaglandin-like substances
Authors: K. HERBACZYNSKA-CEDRO, J. STASZEWSKA-BARCZAK, H. JANCZEWSKA
Journal: Cardiovascular Research (1976)

Experimental evidence for the release of prostaglandin-like substances, mainly of the E type, into the venous outflow from working skeletal muscles in the dog is described. Muscular exercise of the hind-leg produced by sciatic nerve stimulation evoked the release of prostaglandin-like substances detected in femoral venous blood by the bioassay method. This release occurred during and after muscular work, was abolished by indomethacin, and was not present in gallamine-treated dogs. The results suggest that endogenous vasodilator prostaglandins released during and after muscular work may contribute to local hyperaemic response during and, mainly, after muscular activity.
Is general practice in trouble?
Authors: J. Appleby
Journal: BMJ (2014)

John Appleby unpicks the data on funding of primary care

Like other parts of the healthcare system over the past four years, general practice has been under pressure financially. But is it, as the Royal College of General Practitioners’ current campaign suggests, in need of saving1 or, as a recent Nuffield Trust review reports, “in crisis”?2 And, if general practice is in trouble, why do three quarters of the public remain satisfied with it?3

In terms of funding, general practice accounted for around £8.8bn (8%) of total NHS spending in 2013-14. This share has reduced by about 0.7% since 2008-09. It has also reduced in real terms. Between 2005-06 and 2013-14 total investment in general practice fell by 6% in real terms—equivalent to nearly £560m (€710m; $880m, fig 1⇓). Over the period of the current parliament (since 2010-11), it fell by 2.5%. This is in contrast to a real rise in total NHS spending of …
Attitudes to smoking and smoking habit among the staff of a hospital.
Authors: P D Davies, K Rajan
Journal: Thorax (1989)

A survey of the smoking habits and attitudes towards smoking of all staff working in a teaching hospital with a specialist thoracic department has been carried out. Six hundred and sixty three (70%) of the 949 members of staff returned a voluntary self completed questionnaire. Completion rates were highest among medical, administrative, and clerical staff, and lowest among domestic and catering staff. Of the 663 responders, 136 (23%) admitted to being current smokers and 135 (19%) to being ex-smokers. The great majority of responders (81-94%, depending on area of work) believed that more areas of the hospital should be entirely smoking free. Most responders, however, believed that some accommodation should be made available to staff (70%), patients (52%), or visitors (59%) who wished to smoke. About a quarter of smokers expressed interest in joining a group to help them give up smoking.
Letter: Tests for lactose malabsorption in adults.
Authors: R A Frayha, S Uthman
Journal: BMJ (1975)

tion by binding to ristocetin and not by an effect on the platelets or the ristocetin cofactor.There is no evidence that our ob- servation reflects an influence of Haemaccel on the haemostatic mechanism in vivo.All evidence suggests that this inhibition is solely an in-vitro phenomenon.-Weare, etc.,
Importance of asking about glaucoma.
Authors: N C Price
Journal: BMJ (1983)

and may easily displace.Our guard is simple and easy to use even in inexperienced hands.In addition, it is reusable, easy to sterilise, and requires no alterations to existing equipment.Its use should minimise the risk of damage to internal organs during the insertion of pleural drains.We are most grateful for the help and encouragement from the respiratory physicians and thoracic surgeons in the Wessex and South Western Regional Health Authorities.We also thank the department of medical engineering at the Bristol Royal Infirmary for manufacturing the guard and for their helpful advice during its development, and the departments of medical illustration at Southmead Hospital, Bristol, and the Bristol Royal Infirmary.Patent applied for.Guards are available from JEH.
1180 A CHROMOSOME 19 SNP (RS12979860) PREDICTS OUTCOME (EVR/SVR) IN HCV PATIENTS TREATED WITH INTERFERON, INDEPENDENT OF PEGYLATION OR RIBAVIRIN
Authors: T. Asselah, L. Essioux, P. Marcellin, M.W. Fried, D.M. Jensen, S. Germer, R. Benayed, T. Chu, A. Tietz, D. Chin, N. Shulman, J.A. Thommes, M. Laughlin, U. Lopatin
Journal: Journal of Hepatology (2010)
Glycosylated Hemoglobin and Monitoring of Diabetic Control
Authors: RALPH E. BERNSTEIN
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 August 1980Glycosylated Hemoglobin and Monitoring of Diabetic ControlRALPH E. BERNSTEIN, M.B.RALPH E. BERNSTEIN, M.B.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-2-380_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Boden and colleagues (1) have indicated the value of checking glycosylated hemoglobin (glycohemoglobin) during stable and deteriorating periods of diabetic control but conclude that hemoglobin (Hb) A1assay is not useful for detecting rapidly improving metabolic states. Nevertheless, this information can be obtained by a simple stratagem, using the same analytic method of cation-exchange chromatography. It involves centrifuging an aliquot of the blood and preparing a dialysed hemolysate for Hb A1assay of the top 10% fraction of the erythrocyte column (2); this contains reticulocytes (the 0.9% of normal whole blood is enhanced to 6% or more...References1. BODENMASTERGORDONSHUMANOWEN GRSCO. Monitoring metabolic control in diabetic outpatients with glycosylated hemoglobin. Ann Intern Med. 1980;92:357-60. LinkGoogle Scholar2. BERSTEIN R. Glycosylated hemoglobins: hematologic considerations determine which assay for glycohemoglobin is advisable. Clin Chem. 1980;26:174-5. CrossrefMedlineGoogle Scholar3. BERNSTEIN R. Alterations in metabolic energetics and cation transport during aging of red cells. J Clin Invest. 1959;38:1572-86. CrossrefMedlineGoogle Scholar4. GUTHROWMORRISDAYTHORPEBAYNES CMJSJ. Enhanced nonenzymatic glycosylation of human serum albumin in diabetes mellitus. Proc Nat Acad Sci USA. 1979;76:4258-61. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Amber Research 2196 Johannesburg South Africa PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNonenzymatically Glycosylated Proteins 1 August 1980Volume 93, Issue 2Page: 380-380KeywordsBloodChromatographyHemoglobinReticulocytes Issue Published: 1 August 1980 PDF DownloadLoading ...
Apoptosis and tumor necrosis factor alpha levels in chronic hepatitis C parallel the histological activity index
Authors: M.G. Neuman, J.P. Benhamou, P. Marcellin, I. Malkiewicz, H. Schmilovitz-Weiss, Z. Ben-Ari, M. Bourliere, D. Valla, G.G. Katz
Journal: Journal of Hepatology (2003)
In my chosen doctor I trust
Authors: David Mechanic
Journal: BMJ (2004)

Avogadro's number, leaving nothing behind but their memory.The homoeopathic version of bottled water, which has had negative memories removed and replaced with beneficial energy patterns, is called "Blue Water" and sells for £11 a litre.But consumers can only take so much purity.Bottled water has also become an "aquaceutical," the ultimate health food.It is now fortified with additives and produced using special processes claimed to improve health.Nestlé, the maker of Contrex bottled water, says its product contains traces of calcium and magnesium that help reduce weight, eliminate toxins, and reduce fatigue.Penta H2O is claimed to have a unique structure with smaller clusters of H 2 O molecules that ensures more efficient absorption of its health giving properties.Superoxygenated waters claim to increase energy levels and concentration by increasing the concentration of oxygen in the blood.Lakeland Willow Spring water, voted best designer water in 2003, contains traces of salicin, which is claimed by the company to be useful for "eliminating toxins."In California, a company is now selling chemical-free bottled water specifically designed for pets.Water can also make people feel very vulnerable when they think it has been tampered with.Water contamination incidents are associated with particular disruption and morbidity, which cannot be explained on toxicological grounds. 2 General Jack Ripper, who believed that fluoridation was a communist plot to poison our "vital body fluids," was a product of Stanley Kubrick's imagination, but his views are only an exaggeration of a widespread concern.The continuing fluoridation controversy confirms that adding anything to public supplies of water causes anxiety.The public is particularly unforgiving when companies produce water that is less than pure.When high concentrations of benzene were found in Perrier, sales plummeted and the company has struggled to regain its market share.The example of Coca Cola is instructive.Bottled Coca Cola was associated with a health scare in Belgium, which was almost certainly an example of mass hysteria. 3 The brand was temporarily
KIR2DS1 genotype predicts for complete cytogenetic response and survival in newly diagnosed chronic myeloid leukemia patients treated with imatinib
Authors: D Marin, I H Gabriel, S Ahmad, L Foroni, H de Lavallade, R Clark, S O'Brien, R Sergeant, C Hedgley, D Milojkovic, J S Khorashad, M Bua, A Alsuliman, A Khoder, K Stringaris, N Cooper, J Davis, J M Goldman, J F Apperley, K Rezvani
Journal: Leukemia (2011)
Drugging the PI3 Kinome: From Chemical Tools to Drugs in the Clinic
Authors: Paul Workman, Paul A. Clarke, Florence I. Raynaud, Rob L.M. van Montfort
Journal: Cancer Research (2010)

Abstract The phosphatidylinositide 3-kinase (PI3K) pathway is very commonly activated in a wide range of human cancers and is a major driving force in oncogenesis. One of the class I lipid kinase members of the PI3K family, p110α, is probably the most commonly mutated kinase in the human genome. Alongside genetic, molecular biological, and biochemical studies, chemical inhibitors have been extremely helpful tools in understanding the role of PI3K enzymes in signal transduction and downstream physiological and pathological processes, and also in validating PI3Ks as therapeutic targets. Although they have been valuable in the past, the early and still frequently employed inhibitors, wortmannin and LY294002, have significant limitations as chemical tools. Here, we discuss the case history of the discovery and properties of an increasingly used chemical probe, the pan-class I PI3K and mammalian target of rapamycin (mTOR) inhibitor PI-103 (a pyridofuropyrimidine), and its very recent evolution into the thienopyrimidine drug GDC-0941, which exhibits excellent oral anticancer activity in preclinical models and is now undergoing phase I clinical trials in cancer patients. We also illustrate the impact of structural biology on the design of PI3K inhibitors and on the interpretation of their effects. The challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the role of structural biology and chemical biology in innovative drug discovery. Cancer Res; 70(6); 2146–57