tbuckley/cabot-search huggingface dataset:
Pituitary-Adrenal Suppression and Cushing's Syndrome After Intermittent Dexamethasone Therapy
Authors: NATHAN B. RABHAN
Journal: Annals of Internal Medicine (1968)

Six patients have been treated with high-dosage dexamethasone every 48 hr for 3 to 29 weeks. Pituitary-adrenal function, as measured by the urinary 17-ketosteroid and 17-hydroxysteroid response to intravenous adrenocorticotrophic hormone during therapy, was significantly depressed in all subjects. Significant metabolic side effects occurred in four of the patients, with two instances of pitting edema. Clinical response was excellent in four patients with sarcoidosis, fair in a patient with the nephrotic syndrome, and poor in a patient with reticulum cell sarcoma. The results of this study with dexamethasone differ from recorded experiences with alternate-day prednisone, which produces few side effects and minimal pituitary-adrenal suppression. Dexamethasone appears to have more potent and prolonged pituitary-adrenal suppressive properties when compared with a 1:6.6 ratio of prednisone. Although the number of cases treated with alternate-day dexamethasone is small, experience to date indicates that pituitary-adrenal suppression and glucocorticoid side effects should be expected at the dose and duration of dexamethasone therapy administered in the present study.
Paraoxonase Polymorphism (Gln192Arg) as a Determinant of the Response of Human Coronary Arteries to Serotonin
Authors: Christophe Bauters, Carole Amant, Agnès Boulier, Philippe Cabrol, Eugène McFadden, Patrick Duriez, Michel E. Bertrand, Philippe Amouyel
Journal: Circulation (2000)

Background —Oxidation of LDL plays a role in endothelial dysfunction. Paraoxonase, an enzyme present on HDL, protects LDL against oxidation. Paraoxonase activity is genetically determined in part, and 3 genotypes have been described with variable enzymatic activity. We hypothesized that the paraoxonase polymorphism might influence endothelial function. Methods and Results —Twenty-seven patients with clinical manifestations of coronary artery disease underwent provocative testing by intracoronary administration of serotonin. None of the coronary arteries studied had significant (&gt;50%) stenosis. Ten patients had the QQ genotype and 17 had the QR genotype. At proximal segments, the mean percentage reduction in lumen diameter in response to serotonin was greater in QQ patients than in QR patients (10 −5 mol/L: P &lt;0.05; 10 −4 mol/L: P &lt;0.006). Similarly, at distal segments, constriction in response to serotonin was greater in QQ patients than in QR patients (10 −6 mol/L: P &lt;0.03; 10 −5 mol/L: P &lt;0.07). Conclusions —These results suggest a higher synthesis or release of endothelium-derived relaxing factors to counteract the vasoconstrictor effect of serotonin in patients with the R allele. These findings provide evidence that the paraoxonase polymorphism may play a role in the regulation of coronary vasomotor tone.
THE RELATION OF THE MIDDLE TURBINATE BODY TO CHRONIC NASAL DISEASES.
Authors: L. H. BAKER
Journal: JAMA (1901)

Chronic nasal catarrh is so prevalent on this side of the Atlantic as to have received the epithet of "the American disease," and the failure of medical men to find means for the cure or amelioration of the disorder has become an opprobrium to the profession and a prominent feature in the bids of the charlatans for patronage. We can not ignore the influence of climate and habits of living among us as the exciting causes, but there are long periods of the year in which these are not especially active in keeping alive the trouble, so we must seek elsewhere for the causes which operate to prevent the natural tendency to spontaneous recovery which exists in the presence of acute nasal disorders. The easy accessibility of the inferior turbinate body, and its proneness to participate in all nasal irritations and respond by swelling and producing nasal obstruction, has made
Lactate release from the subcutaneous tissue in lean and obese men.
Authors: P A Jansson, A Larsson, U Smith, P Lönnroth
Journal: Journal of Clinical Investigation (1994)

Lactate concentration in the subcutaneous interstitial fluid and adipose tissue blood flow (ATBF, ml/100 g.min) were simultaneously measured with the microdialysis technique combined with 133Xe clearance in the abdominal and femoral subcutaneous adipose tissue in nine lean and nine obese men. The studies were performed both in the postabsorptive state and 2 h after an oral glucose load and the results compared to the lactate levels in arterialized venous plasma. After an overnight's fast, arterial lactate was 738 +/- 49 and 894 +/- 69 microM (mean +/- SE) (P < 0.05) in the lean and obese subjects, respectively. The interstitial lactate levels were significantly higher than blood lactate in both subject groups without any regional differences. Abdominal and femoral ATBF was 3.2 +/- 0.6 vs. 2.8 +/- 0.4 and 1.7 +/- 0.3 vs. 2.4 +/- 0.4 ml/100 g.min (P < 0.05) in lean and obese subjects, respectively. Mean apparent lactate release from the abdominal vs. femoral adipose tissue in the fasting state was 10.5 +/- 3.1 vs. 8.6 +/- 2.3 and 6.0 +/- 2.3 vs. 8.5 +/- 2.3 mumol/kg.min (NS) in lean and obese subjects, respectively. Both plasma and interstitial lactate levels increased significantly after an oral glucose load in both subject groups. However, apparent lactate release increased significantly only in the lean group. It is concluded that subcutaneous adipose tissue is a significant source of whole-body lactate release in the postabsorptive state and that this is further enhanced in obese subjects due to their large adipose mass.
BENDAVIA (MTP-131), A NOVEL MITOCHONDRIA-TARGETING PEPTIDE, IMPROVES ACTIVITY AND EXPRESSION OF CYTOCHROME-C OXIDASE AND ATTENUATES MEDIATORS OF CARDIOMYOCYTE APOPTOSIS IN LEFT VENTRICULAR MYOCARDIUM OF DOGS WITH ADVANCED HEART FAILURE
Authors: Hani N. Sabbah, Ramesh C. Gupta, Kristina Szekely, Mengjun Wang, Kefei Zhang, Sharad Rastogi
Journal: Journal of the American College of Cardiology (2013)
Abstract LB-87: Methylated-mediated repression of <i>ZNF154</i> in ovarian cancer is associated with poor overall survival
Authors: Takako Okamoto, Ken Yamaguchi, Zhiqing Huang, Regina Whitaker, Ikuo Konishi, Andrew Berchuck, Susan K. Murphy
Journal: Cancer Research (2012)

Abstract Objectives: Epigenetic gene regulation plays an important role in the development of cancer. We previously found that Zinc Finger Protein 154 (ZNF154), a Krüppel family zinc finger protein, is ubiquitously methylated in a large panel of ovarian cancer cell lines but is unmethylated in normal cells. The objectives of this study were to determine the relevance of ZNF154 methylation to mRNA expression and relationship to clinical outcome in primary epithelial ovarian cancers. Methods: Genomic DNA from 85 ovarian cancers (53 serous, 13 clear cell, 11 endometrioid and 8 mucinous) along with 4 fallopian tube and 4 ovarian surface epithelium specimens was bisulfite modified (Zymo EZ DNA Methylation kit) followed by generation of Illumina Infinium 450k Methylation Beadchip data for &amp;gt;485,000 CpG sites, given as β-values (scale, 0-1, where 1 is completely methylated). Bisulfite pyrosequencing was used to validate array results. ZNF154 mRNA expression was quantified using real time RT-PCR following treatment of 5 ovarian cancer cell lines and 2 immortalized OSE controls with 5µM 5-aza-2′ deoxycytidine (DAC) for 72h. Mann-Whitney U tests were used for group comparisons, Pearson correlation for continuous variables and the Kaplan-Meier method for overall survival. Results: Methylation of ZNF154 was significantly higher in cancers versus normal tissues (average β=0.51 versus β=0.09, respectively; p&amp;lt;0.0001). Methylation values obtained by pyrosequencing strongly correlated with array β-values (R=0.94; p=1.31e-40). ZNF154 mRNA expression was lower in ovarian cancer versus normal cells (p=0.015). Following DAC treatment, ZNF154 expression increased an average 8.01-fold (p=0.0499) while methylation levels decreased up to 20% (p=0.028) compared to mock treated controls. Stage III-IV serous cancers with higher (N=25) versus lower (N=22) ZNF154 methylation had 66 months decreased median overall survival (p=0.032). Conclusions: ZNF154 is ubiquitously methylated in primary ovarian cancers but not in normal cells and expression of ZNF154 is at least partially regulated by DNA methylation. In addition, increased methylation of ZNF154 is associated with poor clinical outcome for advanced stage serous cancers. Our results suggest that ZNF154 methylation status may have utility as a biomarker and also as a tool for prognostic prediction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-87. doi:1538-7445.AM2012-LB-87
P237 Does desaturation on exercise predict nocturnal hypoxia in children with cystic fibrosis?
Authors: J. Keating, N. Collins, M. Rosenthal, A. McKee, D. Urquhart
Journal: Thorax (2011)

<h3>Introduction</h3> Exercise induced arterial hypoxia (EIAH) is well documented in cystic fibrosis (CF); though its relationship with nocturnal hypoxia remains unclear. In adult CF, hypoxia occurs more frequently during sleep than exercise,12 but this has not been investigated in children. <h3>Aim</h3> To identify whether EIAH is a reliable predictor of nocturnal hypoxia in CF children. <h3>Methods</h3> Retrospective case note review of 34 children with CF. All performed the modified shuttle test,3 overnight pulse oximetry and spirometry in the second week of an elective admission for intravenous antibiotics. EIAH was defined as drop in SpO<sub>2</sub> ≥4% from baseline.4 There is no agreed definition of nocturnal hypoxia, we assessed numerous overnight variables, mean and lowest SpO<sub>2</sub> and % time with SpO<sub>2</sub> &lt;92% in sleep. Data were analysed using SPSS software (SPSS). <h3>Results</h3> 34 subjects were assessed, median age 12 (range 7–16) years, and FEV<sub>1</sub> 72 (25–103) % predicted. Nine demonstrated EIAH and five had nocturnal desaturation (SpO<sub>2</sub> &lt;92% &gt;10% sleep time). All children with SpO<sub>2</sub> &lt;92% for &gt;10% of sleep also had EIAH, this was significant (p=0.0086). The relationship between nocturnal hypoxia and lowest exercise SpO<sub>2</sub> (p=0.0076) was also significant. However, 6 of those with EIAH were not hypoxic overnight. The sensitivity of EIAH detecting sleep hypoxia was 75% and specificity 80%. Positive predictive value (PPV) was 33% and negative predictive value 96%. <h3>Conclusion</h3> The PPV of EIAH for detecting nocturnal hypoxia is poor, but the definition of EIAH must be questioned. SpO<sub>2</sub> varying from 90% to 87% does not meet EIAH criteria, yet a fall from 97% to 93% does. We must also note that although the relationship between nocturnal hypoxia and EIAH appears significant the number of subjects in this group is extremely small. We conclude EIAH is not a reliable predictor of nocturnal desaturation and advocate a sleep study to confidently detect sleep hypoxia.
WHAT SHOULD A PATIENT WITH ARTHRITIS EAT?
Authors: WALTER BAUER
Journal: JAMA (1935)

A time-honored question with physicians as well as with laymen is What should a patient with arthritis eat? If the type of diet prescribed for patients with arthritis is any criterion in answering this question, one is forced to conclude one of two things: (1) that the diet indicated varies considerably from patient to patient or (2) that there exists no unanimity of opinion concerning the correct dietary for an arthritic patient. <h3>CLASSIFICATION AND DIAGNOSIS OF JOINT DISEASES</h3> Any discussion of the dietary in arthritis cannot be adequately presented without stressing the fact that an accurate diagnosis is the first requisite. In other words, the physician's first duty, when confronted with a patient complaining of symptoms referable to the skeletal system, is to determine whether or not the patient has arthritis, and if so, what type. Therefore, some simple, workable classification of joint disease should be followed by all. The
Comparison of the cardiocirculatory effects of exercise and isoproterenol in children with pulmonary or aortic valve stenosis.
Authors: N J Truccone, C N Steeg, R Dell, W M Gersony
Journal: Circulation (1977)

Isoproterenol infusion during cardiac catheterization as a simulator of exercise was evaluated with hemodynamic studies in children with pulmonary (15) or aortic (8) valve stenosis. Cardiac function was monitored during rest, mild exercise and isoproterenol infusion. Similar heart rates were maintained in both procedures. Peak pulmonary and aortic valve gradients as well as right and left ventricular dp/dt/p were significantly higher and cardiac index significantly lower with isoproterenol as compared to exercise. Isoproterenol induced a significantly greater decrease in systemic vascular resistance, and systemic blood pressure than did exercise. Left ventricular systolic pressure rose to similar levels and this resulted in substantially higher peak aortic gradients with isoproterenol. A consistent correlation was observed for peak valvular gradients measured during exercise and isoproterenol in both groups of patients. Accordingly, regression equations were obtained allowing reasonably accurate prediction of exercise valvular gradients on the basis of the isoproterenol data.
Attenuation of dysfunction in the postischemic 'stunned' myocardium by dimethylthiourea.
Authors: R Bolli, W X Zhu, C J Hartley, L H Michael, J E Repine, M L Hess, R C Kukreja, R Roberts
Journal: Circulation (1987)

The mechanism for the prolonged contractile dysfunction observed in myocardium reperfused after reversible regional ischemia ("stunned" myocardium) is unclear. Recent studies suggest that myocardial stunning may be mediated by oxygen-derived free radicals, but the precise molecular species involved remain unknown. Thus we explored the role of the highly cytotoxic hydroxyl radical in regional postischemic dysfunction by using dimethylthiourea (DMTU), an effective and highly permeable hydroxyl radical scavenger. Open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery followed by 4 hr of reperfusion received either DMTU (0.5 g/kg iv over 45 min starting 30 min before occlusion, n = 14) or saline (n = 15). Control and treated dogs were comparable with respect to variables that may affect postischemic dysfunction, including heart rate, aortic pressure, left atrial pressure, arterial blood gases and hemoglobin concentration, size of the occluded bed (determined by postmortem perfusion), and collateral blood flow (determined by radioactive microspheres). Regional myocardial function was assessed by measuring wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during ischemia. After reperfusion, however, wall thickening (expressed as percent of baseline) was considerably greater in treated as compared with control dogs: 53 +/- 9% (mean +/- SEM) vs 9 +/- 14% (p less than .03) at 1 hr, 55 +/- 9% vs 23 +/- 13% (p less than .05) at 2 hr, 60 +/- 9% vs 28 +/- 14% (p less than .05) at 3 hr, and 67 +/- 5% vs 36 +/- 13% (p less than .05) at 4 hr. Thus DMTU produced a significant and sustained improvement in recovery of contractile function. In concentrations greater than the plasma levels attained in vivo, DMTU did not scavenge either hydrogen peroxide or superoxide anion in vitro. These results suggest that the myocardial dysfunction occurring after a brief episode of regional ischemia is mediated in part by the hydroxyl radical.
Survival after Cardiopulmonary Resuscitation in Babies of Very Low Birth Weight
Authors: J D Lantos, S H Miles, M D Silverstein, C B Stocking
Journal: New England Journal of Medicine (1988)

We conducted a retrospective study of outcome after cardiopulmonary resuscitation (CPR) in babies of very low birth weight. Of 158 such babies (birth weight, less than 1500 g) admitted to a neonatal intensive care unit in 1985, 49 (31 percent) underwent CPR. Low birth weight, low Apgar scores, birth asphyxia, pulmonary interstitial emphysema, hyaline membrane disease, and severe intraventricular hemorrhage were associated with the need for CPR. None of the 38 babies who received CPR in the first three days of life survived. Four of the 11 babies who received CPR after the first 72 hours survived. Three of the four survivors had residual neurologic deficits. Survival rates after CPR in infants of very low birth weight are lower than those in older children or adults. CPR may therefore be considered a nonvalidated therapy in this population. If the results of our study are confirmed, CPR should not be instituted automatically in very-low-birth-weight babies as though it were a validated treatment. Instead, it should be administered upon parents' advance informed consent to experimental treatment.
Abstract 4889: Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck.
Authors: Koichi Sakakura, Takaaki Murata, Kazuaki Chikamatsu
Journal: Cancer Research (2013)

Abstract Recent progression in the understanding of stem cell biology has greatly facilitated the identification and characterization of cancer stem cells (CSCs) from various tumors. In squamous cell carcinoma of the head and neck (SCCHN), various cell surface markers, including CD44, CD133 and ALDH1, have been identified as the potential markers to isolate CSCs. Evidence has accumulated indicating that conventional cancer treatments are potentially ineffective against CSCs. Histone deacetylase inhibitors (HDACi) have multiple biologic effects consequent to alteration in patterns of acetylation of histones and are promising new group of anticancer agents. In this study, we investigate the effects of two HDACi, suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) on two CD44+ cancer stem-like cell lines from SCCHN cultured in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. SAHA and TSA inhibited the growth of SCCHN cell lines in a dose dependent manner as measured by MTS assays. Moreover, SAHA and TSA induced G2/M cell cycle arrest and apoptosis in these SCCHN cell lines. Interestingly, the expression of cancer stem cell markers, CD44 and ABCG2 on SCCHN cell lines were decreased by SAHA or TSA treatment. HDACi also decreased the mRNA expression levels of stemness-related genes (Notch and Nanog) and TGF-β. As expected, HDACi markedly increased the expression of E-cadherin. In addition, the combination of HDACi and chemotherapeutic agents, including cisplatin and docetaxel had a synergistic effect on SCCHN cell lines. Taken together, our data indicate that HDACi not only inhibit the growth of SCCHN cell lines by inducing apoptosis and cell cycle arrest, but also alter stem-like properties of the SCCHN cells, raising the possibility that HDACi may have therapeutic potentials for cancer stem cells of SCCHN. Citation Format: Koichi Sakakura, Takaaki Murata, Kazuaki Chikamatsu. Alteration of cancer stem cell-like phenotype by histone deacetylase inhibitors in squamous cell carcinoma of the head and neck. [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 4889. doi:10.1158/1538-7445.AM2013-4889
Evidence for the involvement of the ATP-sensitive potassium channel in a novel model of hypoxic preconditioning in dogs
Authors: D. A. Mei, G. J. Gross
Journal: Cardiovascular Research (1995)

Journal Article Evidence for the involvement of the ATP-sensitive potassium channel in a novel model of hypoxic preconditioning in dogs Get access David A. Mei, David A. Mei Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Garrett J. Gross Garrett J. Gross * Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA *Corresponding author. Tel. (414) 456 8627; Fax (414) 266 8460. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 2, August 1995, Pages 222–230, https://doi.org/10.1016/S0008-6363(95)00023-2 Published: 01 August 1995 Article history Received: 09 January 1995 Accepted: 27 March 1995 Published: 01 August 1995
Chest Pain Not Always What It Seems; Panic Disorder May Be Cause in Some
Authors: Chris Raymond
Journal: JAMA (1989)

UP TO ONE THIRD of persons referred for coronary angiography have normal angiograms. Many of those persons may actually be suffering from panic disorder, according to a Seattle investigator. "With better training of primary care physicians, we may be able to screen out these persons" and avoid costly and potentially dangerous angiograms, says Wayne Katon, MD. Proper diagnosis would also facilitate more effective treatment, he says. <h3>Other Explanations Possible</h3> Others caution that there can be explanations for chest pain besides psychiatric problems. "As a group, patients with chest pain and normal angiograms are a heterogeneous population, and there is no one explanation," says Richard O. Cannon, MD, co-director of the Cardiovascular Diagnosis Section of the National Heart, Lung, and Blood Institute in Bethesda, Md. Cannon has been assessing a group of such patients with normal angiograms and is finding evidence for a still controversial disorder he calls "microvascular angina." Katon,
Use of poly(ortho esters) for the controlled release of 5-fluorouracyl and a LHRH analogue
Authors: J. Heller, S.Y. Ng, D.W. Penhale, B.K. Fritzinger, L.M. Sanders, R.A. Burns, M.G. Gaynon, S.S. Bhosale
Journal: Journal of Controlled Release (1987)
Dyskeratosis congenita. Report of a large kindred
Authors: J.M. CONNOR, R.H. TEAGUE
Journal: British Journal of Dermatology (1981)

This kindred includes six males with dyskeratosis congenita. It is the largest British pedigree so far reported and brings the total number of reported cases to fifty‐nine. Our pedigree supports X‐linked recessive inheritance and close linkage with the Xg2 locus was excluded. Three previously unreported complications are noted; Hodgkin's disease, adenocarcinoma of the pancreas and deafness. Normal chromosomal stability was found in three patients and immunological studies precluded an early universal defect in cell‐mediated immunity.