tbuckley/cabot-search huggingface dataset:
Point: Oral Hypoglycemic Agents Should Not Be Used to Treat Diabetic Pregnant Women
Authors: Lois Jovanovic
Journal: Diabetes Care (2007)

Studies in pregnancy indicate that the most important glucose concentration throughout the day is the peak postprandial glucose response; i.e., it is the highest blood glucose of the day, not the average, that predicts risk of untoward effects. The Diabetes in Early Pregnancy (DIEP) Study was a multicenter, case-controlled trial of type 1 diabetic women compared with healthy control women throughout pregnancy. Along with the primary objective of relating maternal glucose to risk of spontaneous abortions and malformations, they also studied the relationship between maternal postprandial glucose concentrations and risk of neonatal macrosomia (1). The DIEP Study identified 28.5% of infants from diabetic mothers who were above the 90th percentile of infant birth weight. Birth weight correlated positively with first-trimester maternal fasting blood glucose and A1C. When adjusted for fasting blood glucose and A1C, the 1-h postprandial maternal blood glucose concentration in the third trimester was an even stronger predictor of infant birth weight and fetal macrosomia. In addition, they reported that the risk of macrosomia is a continuum. They showed that any postprandial glucose peak was associated with an increased risk of macrosomia above the 10% risk seen in the general population.

Combs et al. (2) confirmed the findings of the DIEP Study and added the observation that elevated postprandial glucose was associated with an increased rate of macrosomia when higher maternal postprandial glucose concentrations were observed between weeks 29 and 32 of gestation. In a study of gestational diabetic women who failed a trial of diet and thus required insulin therapy, De Veciana et al. (3) described improved fetal outcome with less risk of neonatal hypoglycemia, macrosomia, and Caesarean delivery in women with gestational diabetes mellitus (GDM) when the women were managed by controlling 1-h postprandial glucose concentrations as opposed to action only based on preprandial glucose concentrations. …
Myocardial infarction and the G.P.
Authors: L. C. Bousfield, J. N. Mickerson, J. D. Whiteside
Journal: BMJ (1970)

MEBRITJSHgo home, having no obvious sequelae.His liver function tests, electrolytes, and urea were repeated on the day of his discharge and all were normal.Glibenclamide and its metabolites are more than 970' bonded by serum proteins.About 25 °, of radioactive glibenclamide is excreted in the faeces and the rest in the urine.In contrast to chlorpropamide, the hypoglycaemic reaction to glibencamide is not protracted and is easily controlled by a reduction of the dosage.It is interesting to note phenformin has no hypoglycaemic action in normal people, but this is obviously not so in glibenclamide.This patient's recovery appeared to be fairly rapid and without any immediate damage to kidneys or liver as judged by crude tests of liver function, electrolytes, and urea.
Geographic Factors and the Release of Patients from State Mental Hospitals
Authors: PETER WEISS, JACQUELINE MACAULAY, ALLEN PINCUS
Journal: American Journal of Psychiatry (1966)

The decision to release a patient from a state hospital may be influenced by social as well as clinical factors. In this study of patients admitted for the first time to two state hospitals in Wisconsin, it was revealed that an increase in geographic distance between the hospital and the patient's home was associated with an increase in the period of confinement, increase in the likelihood of conditional release, more stringent clinical standards allowable for release, and a greater probability of receiving chemotherapy. The authors conclude that the hospital's need for certainty in its release decisions increases with geographic distance from the patient's home.
Abstract 5075: PI3K activation restores KrasG12D oncogenic ability in a mouse model of follicular thyroid cancer by directly opposing multiple Kras-initiated negative feedback signals
Authors: Mariavittoria Dima, Kristen Baker, Antonio Di Cristofano
Journal: Cancer Research (2010)

Abstract Activating mutations of Ras family members and aberrant activation of the PI3K/AKT pathway are quite common in thyroid cancer originating from the follicular epithelium. We have recently shown in a relevant in vivo model that, contrary to many other cell types, Kras activation is unable to induce oncogenic transformation of the thyroid follicular cells. However, PI3K activation is able to potently cooperate with Kras oncogenic mutation, thus inducing aggressive and metastatic thyroid follicular carcinomas. We now show that one key event mediated by PI3K in this cross-talk is the inhibition of multiple Kras-initiated negative feedback signals shutting down MAPK signaling and the induction of proliferation. Through these mechanisms, PI3K signaling restores Kras-initiated MAPK activation, induction of proliferation, and oncogenic transformation. In particular, our data reveal that activation of p38α MAPK, as well as up-regulation of MKP2 and MKP3 phosphatases, play a pivotal role in mediating the growth-suppressive negative feedback initiated by Kras oncogenic activation. Activation of p38α MAPK acts by inducing cell cycle arrest and the establishment of cellular senescence, while MKP2 and MKP3 stunt ERK1/2 activation through direct dephosphorylation of these kinases. Strikingly, we have found that PI3K acts through Akt1 (but not Akt2) to potently suppress p38 phosphorylation and activation. Furthermore, PI3K activation results in the transcriptional repression of MKP2 and MKP3 promoters. Through these two molecular mechanisms, PI3K activation contributes to unleashing to its full extent Kras oncogenic ability. These data not only uncover novel oncogenic pathways controlled by PI3K signaling, but also further strengthen the rationale for the dual targeting of PI3K and MAPK pathways in thyroid cancer. 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 5075.
Beneficial effect of dexamethasone on the "no reflow" phenomenon in canine myocardium
Authors: S. H NELLIS, B. H ROBERTS, E. L KINNEY, J. FIELD, A. UMMAT, R. ZELIS
Journal: Cardiovascular Research (1980)

The purpose of the present study was to determine if pretreatment with dexamethasone 6 mg.kg-1 would preserve coronary artery blood flow during reperfusion, thus preventing the no reflow phenomenon. Blood flow to small segments of the left ventricle was measured by the use of 15 micrometer tracer microspheres in intact dog hearts. During 2 hours of occlusion of the anterior descending coronary artery by balloon catheter, dexamethasone produced a small increase of the blood flow to perfused myocardium, when compared with untreated animals; this effect was not seen in underperfused segments of the myocardium. In nontreated animals, reperfusion of the underperfused portion of the left ventricle did not lead to a restoration of flow to normal when measured 1 hour later. In fact, the "no reflow" phenomenon resulted in a post reperfusion left ventricular segment which was similar to that measured during coronary arterial occlusion. However in the dexamethasone treated animals there was a decrease in the extent of left ventricular underperfusion from 19 to 6%. It is concluded that dexamethasone protects the border zone of canine myocardium during occlusion, and prevents the no reflow phenomenon in underperfused regions during reperfusion
A Capsule History of Pain Management
Authors: Marcia L. Meldrum
Journal: JAMA (2003)

Pain is a complex clinical problem. Assessment depends on verbal report, and the patient's physical perceptions may be modified by cognitive and affective factors. The salience of pain as a problem in its own right has grown since 1945 and new therapeutic alternatives have developed from research and from new theoretical perspectives. This short historical review of the highlights of the history of pain management gives particular emphasis to the 20th century and to chronic and cancer pain.
Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients
Authors: René Baudrand, José Miguel Domínguez, Cristian A. Carvajal, Arnoldo Riquelme, Carmen Campino, Stefano Macchiavello, Milan Bozinovic, Mauricio Morales, Margarita Pizarro, Nancy Solis, Alex Escalona, Camilo Boza, Marco Arrese, Carlos E. Fardella
Journal: Metabolism (2011)
IgG subclasses in acne vulgaris
Authors: D.B. HOLLAND, E. INGHAM, G. GOWLAND, W.J. CUNLIFFE
Journal: British Journal of Dermatology (1986)

IgG subclasses were measured in male patients with very low grade or severe acne. No IgG subclass deficiencies were found. Patients with severe acne had a significant increase in total IgG attributable to their exposure to antigens which stimulate the production of antibodies in the IgG2 and IgG3 subclasses.
Group 2 innate lymphoid cells facilitate sensitization to local, but not systemic, TH2-inducing allergen exposures
Authors: Matthew J. Gold, Frann Antignano, Timotheus Y.F. Halim, Jeremy A. Hirota, Marie-Renee Blanchet, Colby Zaph, Fumio Takei, Kelly M. McNagny
Journal: Journal of Allergy and Clinical Immunology (2014)
Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis
Authors: Joseph Hinchey, Sunhee Lee, Bo Y. Jeon, Randall J. Basaraba, Manjunatha M. Venkataswamy, Bing Chen, John Chan, Miriam Braunstein, Ian M. Orme, Steven C. Derrick, Sheldon L. Morris, William R. Jacobs, Steven A. Porcelli
Journal: Journal of Clinical Investigation (2007)

The inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. We show that inactivation of the secA2 gene in Mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of mycobacterial superoxide dismutase. Deletion of secA2 markedly increased priming of antigen-specific CD8+ T cells in vivo, and vaccination of mice and guinea pigs with a secA2 mutant significantly increased resistance to M. tuberculosis challenge compared with standard M. bovis bacille Calmette-Guérin vaccination. Our results define a mechanism for a key immune evasion strategy of M. tuberculosis and provide what we believe to be a novel approach for improving mycobacterial vaccines.
Treatment of Homozygous Protein C Deficiency and Neonatal Purpura Fulminans with a Purified Protein C Concentrate
Authors: Marie Dreyfus, Jean François Magny, Françoise Bridey, Hans Peter Schwarz, Claude Planché, Michel Dehan, Gilbert Tchernia
Journal: New England Journal of Medicine (1991)

PROTEIN C is a vitamin K—dependent glycoprotein circulating in plasma as an inactive zymogen.1 It is converted to the serine protease—activated protein C, a natural anticoagulant that inactivates factors V and VIII after they are activated by thrombin during the coagulation process.2 , 3 The homozygous and double heterozygous forms of congenital protein C deficiency can result in life-threatening neonatal thrombosis and purpura fulminans, diseases that are frequently associated with disseminated intravascular coagulation.4 , 5 At least 19 cases have been reported.4 , 6 7 8 9 10 11 The predominant clinical signs of purpura fulminans consist of ecchymotic skin lesions that spontaneously become necrotic.12 , 13 We describe the case of an . . .
Monoblastic leukemia in an HIV-infected patient: Absence of viral expression in RNA blasts
Authors: C. Guillemain, F. George, M. Courcoul, C. Dhiver, C. Brunet, B. Spire, N. Horschowski, M. Conciatori, J. Sampol
Journal: American Journal of Hematology (1996)

A small number of patients seropositive for the human immunodeficiency virus (HIV) have been reported as developing acute non-lymphoblastic leukemia (ANLL). In the cases previously published, the authors never reported a study of the link joining HIV infection and leukemia. We describe here the case of a 41-year-old HIV positive patient who developed ANLL (FAB classification M5). Using molecular techniques, we looked for a direct link between these two co-existing diseases. We showed the absence of HIV expression in the malignant clone, suggesting that the association of ANLL and Acquired Immune Deficiency Syndrome is not a direct consequence of the myeloid precursors infection. Nevertheless a relationship may exist through a disorganization of the bone marrow micro-environment. © 1996 Wiley-Liss, Inc.
Lymphangitic Spread of Breast Carcinoma: Scintigraphic Pattern With Chest X-ray and Computed Tomography Correlation
Authors: Deborah L. Stein, Leonard M. Freeman
Journal: Clinical Nuclear Medicine (2005)

Lymphangitic spread of metastases has distinct patterns on pulmonary scintigraphy and radiographic imaging. A 43-year-old woman with metastatic breast cancer presented with shortness of breath. Symptomatology was studied with ventilation and perfusion (V/Q) scintigraphy, chest radiograph, and computed tomography (CT). The scintigraphic pattern is consistent with prior descriptions of lymphangitic spread of tumor. The chest x-ray and CT were both performed within the prior 2 months and were confirmatory.
Campaign for Diabetic Ketoacidosis Prevention Still Effective 8 Years Later
Authors: Maurizio Vanelli, Giovanni Chiari, Silvia Lacava, Brunella Iovane
Journal: Diabetes Care (2007)

Diabetic ketoacidosis (DKA) in children with type 1 diabetes at onset is considered an increased risk factor of death and is generally related to a long duration of misdiagnosed hyperglycemia-associated symptoms (1). Shortening this latency period could be a winning preventive strategy. In the period of 1991–1997, we investigated this hypothesis in the province of Parma and demonstrated that, thanks to a school and physician campaign centered on the earliest symptom of diabetes (nocturnal enuresis in a “dry” child) as reported by 89% of parents, it was possible to prevent DKA (2 …
Hospital Survey and Construction Program in Massachusetts a Five-Year Study
Authors: A. Daniel Rubenstein
Journal: New England Journal of Medicine (1954)

During the year 1947 an unprecedented and far-reaching experiment in hospital administrative research was initiated in Massachusetts and throughout the country. Simultaneously throughout the 48 states, Alaska and the Territory of Hawaii, after a detailed inventory of existing facilities according to a predetermined plan, federal funds became available on a matching basis for hospital and health-center construction. For the first time in the history of the nation hospital building was to be undertaken according to one master plan; what may appear to be unbelievable was the certainty that under the provisions of the Hospital Survey and Construction Act (Public Law . . .
Elderly people and the 1990 act
Authors: F. Namdaran, J. Sherval, M. Bull
Journal: BMJ (1995)

EDITOR,—Victoria Ajayi and colleagues state that “the reduction in the length of hospital stay is consistent with the findings that after the legislation patients were more likely to be in hospital for rehabilitation than awaiting placement.”1 Our experience in Edinburgh seems to confirm this finding.

Since 1988 we have carried out …
CC chemokine receptor 5 and renal-transplant survival
Authors: Michael Fischereder, Bruno Luckow, Berthold Hocher, Rudolf P Wüthrich, Uwe Rothenpieler, Helmut Schneeberger, Ulf Panzer, Rolf AK Stahl, Ingeborg A Hauser, Klemens Budde, Hans-H Neumayer, Bernhard K Krämer, Walter Land, Detlef Schlöndorff
Journal: The Lancet (2001)
Role of Human Valve Interstitial Cells in Valve Calcification and Their Response to Atorvastatin
Authors: Lana Osman, Magdi H. Yacoub, Najma Latif, Mohamed Amrani, Adrian H. Chester
Journal: Circulation (2006)

Background— Calcific aortic valve stenosis is a common disease in the elderly and is characterized by progressive calcification and fibrous thickening of the valve, but the cellular and molecular mechanisms are not fully understood. We hypothesized that human valve interstitial cells (ICs) are able to differentiate into osteoblast-like cells through the influence of defined mediators and that this process can be modulated pharmacologically. Methods and Results— To test this hypothesis, we treated primary cultures of human aortic valve ICs with osteogenic media, bone morphogenic proteins ([BMPs] BMP-2, BMP-4, and BMP-7), and tissue growth factor-β ([TGF-β] TGF-β1 and TGF-β3) for 21 days. These mediators induced osteoblast differentiation of valve ICs by significantly increasing the activity and expression of alkaline phosphatase ([ALP] P &lt;0.001). A cytokine protein array revealed that atorvastatin treatment (100 μmol/L) of human valve ICs caused a downregulation in levels of expression of BMP-2, BMP-6, TGF-β1, and TGF-β3 after 24 hours. In addition, human valve ICs treated with atorvastatin in the presence of osteogenic media showed a significant reduction in ALP activity in comparison to cells treated with osteogenic media only ( P =&lt;0.001). This was further confirmed with immunocytochemical staining of valve ICs, whereby atorvastatin markedly reduced the expression of ALP and osteocalcin induced by osteogenic media in comparison to untreated cells. Conclusions— These findings suggest that human valve ICs are capable of osteoblastic differentiation, by potential mediators which can be pharmacologically targeted by atorvastatin.
Word of warning to junior ophthalmologists
Authors: A. Luff, T. James
Journal: BMJ (1995)

EDITOR,—B Hopkisson highlights the bottleneck that has developed at entry to the ophthalmic registrar grade.1 There are now 81 senior house officers with settled status who have the FRCOphth; fewer than 20 registrar appointments were made last year. It is no surprise that Hopkisson had nine applicants (30%) with two or more higher qualifications. Three years ago a fifth of higher surgical trainees in ophthalmology had both the MRCP and an ophthalmic fellowship (R J Aggarwal et al, annual congress of the Royal College of Ophthalmologists, 1992), but increasing competition has directed many …
Intention to Treat — Initiating Insulin and the 4-T Study
Authors: Graham T. McMahon, Robert G. Dluhy
Journal: New England Journal of Medicine (2007)

The normalization of glucose levels plays an important role in protecting patients with diabetes from complications such as myocardial infarction and stroke. To accomplish this goal, most patients with type 2 diabetes will ultimately require treatment with insulin, since oral antidiabetic drugs become insufficient as insulin production declines. Many diabetologists recommend that insulin therapy be initiated if a patient has a glycated hemoglobin level of more than 7% after having received the maximal dose of two oral agents for more than a few months.1 The question of how to initiate insulin therapy in patients with type 2 diabetes has become . . .
Epoxyeicosatrienoic Acids Contribute With Altered Nitric Oxide and Endothelin-1 Pathways to Conduit Artery Endothelial Dysfunction in Essential Hypertension
Authors: Jeremy Bellien, Michele Iacob, Isabelle Remy-Jouet, Daniele Lucas, Christelle Monteil, Laurence Gutierrez, Cathy Vendeville, Yvonne Dreano, Alain Mercier, Christian Thuillez, Robinson Joannides
Journal: Circulation (2012)

We sought to clarify, using functional and biological approaches, the role of epoxyeicosatrienoic acids, nitric oxide (NO)/reactive oxygen species balance, and endothelin-1 in conduit artery endothelial dysfunction during essential hypertension.Radial artery diameter and mean wall shear stress were determined in 28 untreated patients with essential hypertension and 30 normotensive control subjects during endothelium-dependent flow-mediated dilatation induced by hand skin heating. The role of epoxyeicosatrienoic acids and NO was assessed with the brachial infusion of inhibitors of cytochrome P450 epoxygenases (fluconazole) and NO synthase (N(G)-monomethyl-l-arginine [L-NMMA]). Compared with controls, hypertensive patients exhibited a decreased flow-mediated dilatation in response to postischemic hyperemia as well as to heating, as shown by the lesser slope of their diameter-shear stress relationship. In controls, heating-induced flow-mediated dilatation was reduced by fluconazole, L-NMMA, and, to a larger extent, by L-NMMA+fluconazole. In patients, flow-mediated dilatation was not affected by fluconazole and was reduced by L-NMMA and L-NMMA+fluconazole to a lesser extent than in controls. Furthermore, local plasma epoxyeicosatrienoic acids increased during heating in controls (an effect diminished by fluconazole) but not in patients. Plasma nitrite, an indicator of NO availability, increased during heating in controls (an effect abolished by L-NMMA) and, to a lesser extent, in patients, whereas, inversely, reactive oxygen species increased more in patients (an effect diminished by L-NMMA). Plasma endothelin-1 decreased during heating in controls but not in patients.These results show that an impaired role of epoxyeicosatrienoic acids contributes, together with an alteration in NO/reactive oxygen species balance and endothelin-1 pathway, to conduit artery endothelial dysfunction in essential hypertension.https://www.eudract.ema.europa.eu. Unique identifier: RCB2007-A001-10-53.
Hypoxia Enhances Cellular Proliferation and Inositol 1,4,5-Triphosphate Generation in Fibroblasts from Bovine Pulmonary Artery But Not from Mesenteric Artery
Authors: DAVID J. WELSH, PAMELA SCOTT, ROBIN PLEVIN, RODGER WADSWORTH, ANDREW J. PEACOCK
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

When pulmonary hypertension occurs in the face of hypoxia there is remodeling of all three layers of the pulmonary vessels, but in particular, there is an increase in number of adventitial fibroblasts. Hypoxia causes vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. We hypothesized that there are fundamental differences in oxygen sensing and cell signaling between systemic and pulmonary artery cells in response to hypoxia. Here, we determined the effect of hypoxia either alone or in combination with known growth factors such as serum, endothelin-1 (ET-1), and platelet-derived growth factor (PDGF) on the proliferative responses of bovine pulmonary artery and mesenteric artery fibroblasts. Fibroblasts were obtained from primary cultures. Growth was assessed by [3H]thymidine incorporation. Inositol 1,4,5-triphosphate (IP3) generation was measured using a competitive binding assay. Hypoxia alone increased proliferation of pulmonary artery fibroblasts (611 ± 24%), but not in those from the mesentery. Furthermore, hypoxia had the effect of increasing the replicative response of pulmonary fibroblasts to serum and PDGF, but no change was observed in the mesenteric cells. ET-1 had no effect on growth of either cell type. PDGF gave rise to a significant elevation in IP3 production under hypoxic conditions in the pulmonary artery cells (234%), but not in the mesenteric cells. ET-1 caused no change in IP3 production in any cell type. These data suggest that hypoxia sensitizes pulmonary artery fibroblasts to the proliferative effect of mitogens through a pathway that is not present, or is present but repressed, in the mesenteric cells.
Home testing kit allows parents to detect their childrens drug misuse
Authors: X. Bosch
Journal: BMJ (2002)

An over the counter home screening kit, intended for parents to detect drug misuse in their children, went on sale in Spanish pharmacies last week. But critics say that using the kit without the suspected drug user's knowledge is not the best way for parents to tackle the issue.

At a cost of €60 (£38; $16), the new single use kit contains five test strips, which can be rubbed or wetted with fluid from the suspected misuser. It takes …