tbuckley/cabot-search huggingface dataset:
Congenital adrenal hyperplasia and adult sexual behavior
Authors: C. J. Johnson
Journal: JAMA (1997)

To the Editor.  —In the Commentary on the safety of long-term prenatal glucocorticoid treatment, Drs Seckl and Miller 1 state,  it has been suggested that fetal androgens can 'masculinize' the human brain, as adult females with CAH [congenital adrenal hyperplasia] have a higher incidence of lesbianism, less interest in sexual activity, and a negative body image; prenatal dexamethasone may diminish this potential action of fetal androgens. This implies that being a lesbian is a masculinized state and also is a negative outcome. Clearly there is much to be learned about human behavior, and studies that further our knowledge should be applauded. However, homosexuality is not a pathologic condition and should not be framed as such in the medical literature. Furthermore, lesbians are not masculinized women. The perpetuation of these negative stereotypes is a disservice to all gay and lesbian colleagues and patients.
Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease
Authors: Motoko Koyama, Rachel D Kuns, Stuart D Olver, Neil C Raffelt, Yana A Wilson, Alistair L J Don, Katie E Lineburg, Melody Cheong, Renee J Robb, Kate A Markey, Antiopi Varelias, Bernard Malissen, Günter J Hämmerling, Andrew D Clouston, Christian R Engwerda, Purnima Bhat, Kelli P A MacDonald, Geoffrey R Hill
Journal: Nature Medicine (2011)
Treatment of small cell lung cancer by pneumonectomy and single course high dose chemotherapy.
Authors: T J Littlewood, A P Smith, D P Bentley
Journal: Thorax (1987)

It is generally accepted that the treatment of choice for patients with small cell lung cancer is combination chemo- therapy, after which up to 80% of patients will achieve a complete or partial response.'Most of these patients will, however, eventually relapse and die from the effects of disseminated tumour.Because of the low cure rate in patients with this disease, new approaches to treatment are important.In this paper we describe two patients with small cell lung cancer who were treated with a total pneu- monectomy followed by high dose chemotherapy and auto- logous bone marrow transplantation.
Abstract P4-07-05: MEDI3379, an antibody against HER3, is active in HER2-driven human breast tumor models
Authors: Z Xiao, R Rothstein, R Carrasco, L Wetzel, K Kinneer, H Chen, D Tice, R Hollingsworth, P Steiner
Journal: Cancer Research (2012)

Abstract HER3 (ERBB3) is a member of the EGFR/HER family of receptor tyrosine kinases (RTK), consisting of EGFR, HER2, HER3 and HER4. Unlike the other HER family members, HER3 lacks intrinsic tyrosine kinase activity and therefore needs to form heterodimers with EGFR, HER2 or other kinase-proficient RTKs to be functionally active. Dimerization is induced by overexpression of EGFR or HER2 in a ligand-independent (LI) manner. In this process HER3 acts as a driver in divergent cancer types including HER2-positive breast cancer (BC) via induction of the PI3K-AKT pathway. Alternatively, heregulin (NRG1/HRG), the major HER3 ligand, induces a conformational shift in HER3 which leads to dimer formation with a partner RTK in a ligand-dependent (LD) manner. We have developed an antagonistic human monoclonal antibody against HER3, termed MEDI3379, and tested it in multiple breast cancer cell lines. We observed effective suppression of constitutive pHER3 and pAKT with MEDI3379, leading to anti-proliferation effects in cell culture models. Preclinical evaluation of MEDI3379 demonstrated antitumor activity in several orthotopic BC xenografts in nude mice which did not express HRG. For example, the BC xenograft model BT474 with amplified HER2 responded to MEDI3379 (65% dTGI). In conclusion, our findings with targeting of HER3 in mouse models support continued development of MEDI3379 for cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-07-05.
Abstract 4382: N-acetylcysteine interacts with Cu++ to induce cancer cell death through the generation of hydrogen peroxide
Authors: Jie Zheng, Jessica R. Lou, Doris M. Benbrook, Marie H. Hanigan, Stuart E. Lind, Wei-Qun Ding
Journal: Cancer Research (2010)

Abstract Metal ionophores that transport copper or zinc into cells are toxic to cancer cells. Loading of metals into cells results in loss of protective intracellular thiols, which can contribute to cell death. We postulated that the metal-thiol interaction might also lead to the generation of cytotoxic compounds. We tested this hypothesis by adding N-acetylcysteine (NAC) to cancer cell lines in the presence of copper or zinc. NAC itself, at concentrations up to 10 mM, was not toxic to a variety of human cancer cell lines, including A2780 (ovarian), MCF-7 (breast), Panc-1 (pancreas), and A375 (melanoma). When added to cells in the presence of Cu++ (3-30 µM), NAC significantly enhanced the cytotoxicity induced by CuCl2 alone. The cytotoxicity of the NAC/copper combination was blocked by the copper-binding compounds tetrathiomolybdate and bathocuproinedisulfonic acid. NAC was not cytotoxic in the presence of zinc. This finding suggested that the redox activity of copper was an important determinant of cytotoxicity and raised the possibility that H2O2 was being generated. This was confirmed in vitro using a colorimetric assay (Biovision). The ability of other thiols to promote H2O2 generation when exposed to Cu++ was then examined. Reduced lipoic acid and L-cysteine generated higher level of H2O2 than NAC did; reduced glutathione was able to generate comparable levels of H2O2 as NAC, while oxidized glutathione generated significantly lower levels of H2O2; oxidized cysteine did not generate H2O2. To determine if H2O2 played a role in the observed cytotoxicity, catalase was added to cells treated with NAC/copper. Its addition completely blocked cell killing, indicating that significant amounts of extracellular H2O2 were being generated. These findings indicate that the interaction of copper with thiols leads to cytotoxic concentrations of H2O2. Thiols may differ in their reactivity with redox active compounds such as copper. Since the copper concentration of plasma is greater than that of tissue culture media, NAC's effects in vivo may differ from those seen in vitro. 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 4382.
BRISKET DISEASE. III. SPONTANEOUS REMISSION OF PULMONARY HYPERTENSION AND RECOVERY FROM HEART FAILURE*
Authors: Hiroshi Kuida, Hans H. Hecht, Ramon L. Lange, Arthur M. Brown, Theofilos J. Tsagaris, Joseph L. Thorne
Journal: Journal of Clinical Investigation (1963)

Previous reports from this laboratory have dealt with the ecologic, pathologic, clinical, and pathophysiologic features of brisket disease (1, 2).On the basis of these studies brisket disease may be defined as altitude-dependent, pulmonary, hy- pertensive heart disease in cattle of the species Bos taiurus.Briefly, the disease in Utah occurs primarily in young calves usually during their first exposure to conditions existing on summer ranges at elevations between 8,000 and 11,000 feet.Typical findings in animals suffering from brisket disease are outlined in Table 1.It was observed that a significant number of animals with acute brisket disease recovered when removed from the mountainous ranges and brought to Salt Lake City, Utah (elevation 4,500 feet).This observation prompted an investiga- tion of the nature, magnitude, and time course of changes in various physiologic parameters associated with clinical recovery.The demon- stration of dramatic remission from pulmonary hypertension and improvement in over-all cardio- vascular function provides the basis for this report.METHOD Over a period of 4 years, 43 venous and 21 left ventricular cardiac catheterization studies were carried out in 14 animals that recovered from brisket disease.These calves were among a group of 42 in which hemodynamic observa- tions were made during acute brisket disease.Five ani- mals were studied twice, six were studied three times, and four separate observations were made on the remaining three.The initial catheterization procedure in each ani-
Arachidonic acid metabolism in inflammatory cells of patients with bronchial asthma
Authors: C. Calabrese, M. Triggiani, G. Marone, G. Mazzarella
Journal: Allergy (2000)

Over the last few years, the demonstration of beneficial effects of leukotriene receptor antagonists in various forms of asthma has renewed clinical and pharmacologic interest in this class of lipid mediators. Several studies demonstrated an increased biosynthesis of cysteinyl leukotrienes (CysLT) in asthmatic patients. However, the reasons for the dysregulated production of CysLTs in asthmatic patients are not completely defined. An improved method of lipid mediator detection and the availability of cells isolated from human airways (by bronchoalveolar lavage [BAL] and bronchial biopsies) have allowed initial studies to address this issue. Eosinophils retrieved from inflamed airways of asthmatics have a larger arachidonic acid (AA) content than their blood counterpart. The high level of AA in these cells is primarily due to a remodeling of endogenous arachidonate pools with the accumulation of this fatty acid in a triglyceride‐associated pool. In addition, elevated levels of a secretory form of phospholipase A 2 , the key enzyme initiating the cascade of CysLTs, are found in the BAL of asthmatics. Finally, eosinophils isolated from the BAL of asthmatics have an increased expression of LTC 4 synthase. The level of expression of this enzyme correlates with the increased amount of CysLTs produced in the airways of these patients. Taken together, these data identify at least two possible mechanisms to explain the excessive CysLT production in asthmatics: an increased content of AA in the glycerolipid pools of inflammatory cells an enhanced activity of key biosynthetic enzymes involved in CysLT synthesis.
US study questions use of black box warning on antidepressants
Authors: David Spurgeon
Journal: BMJ (2006)

The risk of serious attempts at suicide or death by suicide decreases in the weeks after adults start taking antidepressants, a new study has found. The study, which was funded by the US National Institute for Mental Health, also found that the risk of suicidal behaviour after patients start to take the drugs is generally less for the newer types of antidepressant drugs than for the older types ( American Journal of Psychiatry 2006;163: 41-7).

The study's findings run counter to a 2004 advisory by the US Food and Drug Administration, which recommended close observation for emergence of suicidality in all patients treated with 10 newer antidepressants, including fluoxetine (Prozac) and paroxetine (sold in the US as Paxil and in the United Kingdom as Seroxat) ( BMJ 2005;331: 70).

The study looked at the risk of death by suicide and serious attempt at suicide in the acute phase of antidepressant treatment—the first month after treatment begins. It …
Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia
Authors: Judith E. Karp, Tatiana I. Vener, Mitch Raponi, Ellen K. Ritchie, B. Douglas Smith, Steven D. Gore, Lawrence E. Morris, Eric J. Feldman, Jacqueline M. Greer, Sami Malek, Hetty E. Carraway, Valerie Ironside, Steven Galkin, Mark J. Levis, Michael A. McDevitt, Gail R. Roboz, Christopher D. Gocke, Carlo Derecho, John Palma, Yixin Wang, Scott H. Kaufmann, John J. Wright, Elizabeth Garret-Mayer
Journal: Blood (2011)
Robotic Magnetic Navigation for Atrial Fibrillation Ablation
Authors: Carlo Pappone, Gabriele Vicedomini, Francesco Manguso, Filippo Gugliotta, Patrizio Mazzone, Simone Gulletta, Nicoleta Sora, Simone Sala, Alessandra Marzi, Giuseppe Augello, Laura Livolsi, Andreina Santagostino, Vincenzo Santinelli
Journal: Journal of the American College of Cardiology (2006)
Transplantation of Blood Vessels, Organs, and Limbs
Authors: James D. Hardy
Journal: JAMA (1983)

I am particularly privileged to be invited to write a companion piece on the occasion of the republication of Carrel's<i>JAMA</i>article of 1908 (see p 944). On a sunny Sunday morning in 1935-1936, as a premed freshman sitting on the terrace of the Pi Kappa Alpha fraternity house at the University of Alabama in Tuscaloosa, I turned to the rotogravure section of the<i>Birmingham News-Age Herald</i>and saw there a photograph and write-up of Alexis Carrel and Charles A. Lindbergh with their perfusion apparatus, by means of which they had kept a chicken's heart alive for an extended period, I think for months. This article made a memorable impression on me, and I still have it in my collection of memorabilia denoting times, places, and events. How the world turns, now almost 50 years later. The ultimate dimensions of the field of blood vessel anastomosis and organ transplantation, in
Timing of Genome Duplications Relative to the Origin of the Vertebrates: Did Cyclostomes Diverge before or after?
Authors: S. Kuraku, A. Meyer, S. Kuratani
Journal: Molecular Biology and Evolution (2008)

Two rounds of whole-genome duplications are thought to have played an important role in the establishment of gene repertoires in vertebrates. These events occurred during chordate evolution after the split of the urochordate and cephalochordate lineages but before the radiation of extant gnathostomes (jawed vertebrates). During this interval, diverse agnathans (jawless fishes), including cyclostomes (hagfishes and lampreys), diverged. However, there is no solid evidence for the timing of these genome duplications in relation to the divergence of cyclostomes from the gnathostome lineage. We conducted cDNA sequencing in diverse early vertebrates for members of homeobox-containing (Dlx and ParaHox) and other gene families that would serve as landmarks for genome duplications. Including these new sequences, we performed a molecular phylogenetic census using the maximum likelihood method for 55 gene families. In most of these gene families, we detected many more gene duplications before the cyclostome-gnathostome split, than after. Many of these gene families (e.g., visual opsins, RAR, Notch) have multiple paralogs in conserved, syntenic genomic regions that must have been generated by large-scale duplication events. Taken together, this indicates that the genome duplications occurred before the cyclostome-gnathostome split. We propose that the redundancy in gene repertoires possessed by all vertebrates, including hagfishes and lampreys, was introduced primarily by genome duplications. Apart from subsequent lineage-specific modifications, these ancient genome duplication events might serve generally to distinguish vertebrates from invertebrates at the genomic level.
Angiotensin receptor blockade has protective effects on the poststenotic porcine kidney
Authors: Xin Zhang, Alfonso Eirin, Zi-Lun Li, John A. Crane, James D. Krier, Behzad Ebrahimi, Aditya S. Pawar, Xiang-Yang Zhu, Hui Tang, Kyra L. Jordan, Amir Lerman, Stephen C. Textor, Lilach O. Lerman
Journal: Kidney International (2013)
Unique resistance to guanethidine-induced chemical sympathectomy of spontaneously hypertensive rats: a resistance overcome by treatment with antibody to nerve growth factor.
Authors: E M Johnson, R A Macia
Journal: Circulation Research (1979)

The chronic administration of high doses of guanethidine to rats produces complete destruction of the peripheral sympathetic nervous system. In a study of the effect of guanethidine-induced sympathectomy on the development of hypertension is spontaneous hypertensive rats (SHR, Okomoto strain), only a partial sympathectomy could be produced as assessed by biochemical parameters (tyrosine hydroxylase activity in ganglia and tissue norepinephrine concentrations) and by evaluation of response to stimulation of vasomotor outflow in pithed rat preparations. Other strains of rats (Sprague-Dawley, American Wistar, Kyoto Wistar) were uniformly sensitive to guanethidine sympathectomy. The resistance to guanethidine was not due to a lower accumulation of guanethidine in the neurons of SHR. Addition to the guanethidine treatment of low doses of antibody to nerve growth factor (NGF), which itself produced only a modest sympathectomy, resulted in an almost complete sympathectomy. SHR did not become hypertensive when sympathectomized by combined guanethidine-anti NGF. These results show that the sympathetic neurons of SHR differ from those of other strains with respect to sensitivity to guanethidine cytotoxicity and suggest the possibility of a role for NGF in that altered responsiveness.
Unique sensing errors in third-generation implantable cardioverter-defibrillators
Authors: David J. Callans, Bruce G. Hook, Robert B. Kleiman, Raman L. Mitra, Belinda T. Flores, Francis E. Marchlinski
Journal: Journal of the American College of Cardiology (1993)

Third-generation cardioverter-defibrillators appear to be susceptible to unique sensing errors. This study was performed to determine the incidence and types of sensing errors in combination therapy implantable devices.One of the advantages offered by third-generation implantable cardioverter-defibrillators is the combination of bradycardia and antitachycardia pacing and cardioversion-defibrillation capabilities in a single device. The potential for unique sensing errors, those caused by the conflicts presented by combining bradycardia and tachycardia sensing and therapy algorithms in the same device, has not been previously addressed.To determine the incidence of important sensing errors, 61 patients with a combination therapy device (Cadence [Ventritex] and PCD [Medtronic]) were studied for a 25-month period. In addition to surface electrocardiographic recordings during implantation and routine device testing, real-time and stored electrograms recorded from the rate-sensing leads (Cadence) and real-time marker channel recordings (PCD) were reviewed to diagnose sensing errors that resulted in symptoms, device inefficacy or delivery of inappropriate therapy. After recognition, specific reprogramming steps were performed in an attempt to avoid recurrent sensing errors.A total of 13 sensing errors were diagnosed in 12 patients (19.7%); the incidence was similar in both devices. Five distinct categories of sensing errors were identified. After device reprogramming, only one recurrent error occurred in 98 patient-months of follow-up.Important sensing errors occur in approximately 20% of patients with third-generation combination therapy cardioverter-defibrillators. Prompt diagnosis of sensing errors can lead to specific reprogramming steps to avoid recurrent errors.
Incarcerated and Strangulated Inguinal Hernia in First Year of Life
Authors: J. Rendle-Short, C. Havard
Journal: BMJ (1954)

MBJOURNALwas diminishing foetal movements, and caesarean section was thought to be the ideal method for this patient.Mollison and Walker concluded that premature delivery was contraindicated from the consideration of the mortalitv rates in a series of cases, "the choice of treatment being determined by random numbers" (Mollison, Mourant, and Race, 1952).We feel that each case should be treated individually according to its clinical merits.In view of this case, it would seem that there is still a place for premature delivery of the infant in cases of haemo- lytic disease of the newborn.The indication for such treat- ment would be a patient with a history of two or more still- births, whose husband is homozygous, Rh-positive.We suggest that diminution of foetal movements is a symptom of importance, that it requires the case to be treated as an emergency, and that premature delivery should be carried out in a hospital equipped both for replacement transfusion and for the care of premature babies.It also demands the daily supervision of the patient in the last weeks of pregnancy, especially in cases that show by the pattern of their history that they are liable to produce severely affected infants.Mollison and Walker showed that " the total death rate in the 'induced' group is higher than in the group allowed to go to spontaneous delivery."However, in our experience premature delivery can produce a live birth instead of a stillbirth; and, even though the baby is premature, kernic- terus can usually be prevented by one or more adequate replacement transfusions.In the group of severely affected cases of haemolytic disease of the newborn there is the opportunity of rearing a normal living child by premature delivery, and to achieve this the complete co-operation of the obstetrician and paediatrician is essential.Summary A case of rhesus iso-immunization of severe type is described.After several stillbirths, two living babies were de- livered prematurely by caesarean section.The symptom of diminution of foetal movements in two severely affected babies is described.This symptom is an indication for premature delivery of the foetus in order to prevent another stillbirth and in order to give a possibility of survival.With the close co-operation of the obstetrician and paediatrician this can be achieved.We acknowledge the help given by Dr. W. Weiner, of the Birmingham Regional Blood Transfusion Service, and the medical and nursing staffs of Solihull and Sorrento Hospitals, who so willingly assisted in the care of this patient and her babies.
Low-dose ovine corticotropin-releasing hormone stimulation test in diabetes mellitus with or without neuropathy
Authors: Vittorio Coiro, Riccardo Volpi, Luigi Capretti, Guglielmina Speroni, Paolo Caffarra, Augusto Scaglioni, Laura Malvezzi, Aurelio Castelli, Giovanni Caffarri, Giuseppe Rossi, Paolo Chiodera
Journal: Metabolism (1995)
Hypercholesterolemia in Elderly Persons: Resolving the Treatment Dilemma
Authors: Margo A. Denke, Scott M Grundy
Journal: Annals of Internal Medicine (1990)

Of all age groups, men and women over 60 years of age have the highest prevalence of elevated serum cholesterol levels. Now that detection and treatment of high serum cholesterol levels are increasing, we need a rational approach to managing elevated cholesterol levels in elderly patients. Recent data indicate that high total cholesterol and low-density lipoprotein levels predict risk for coronary heart disease in patients over 60 years of age. However, selecting appropriate candidates for cholesterol-lowering therapy requires clinical judgment of the relative risks and benefits of each therapy and consideration of each patient's overall health status as well as of competing risks. Active medical management of high cholesterol levels, therefore, should be restricted to a limited fraction of elderly patients who are most likely to benefit from long-term therapy. The first line of treatment is diet modification; however, drug therapy for appropriate patients is not contraindicated because of age alone.
"Snake" flexible arm.
Authors: I. Donald, G. D. Green, W. H. Bain
Journal: BMJ (1968)

The idea of a stainless steel flexible arm which can be fixed quite simply by tightening a couple of screws was originally conceived by one of us (G.D. G.) for holding aortic valves " in space " during suturing processes.Its design was under consideration in the mechanical workshops of the Department of Clinical Physics and Bio- Engineering when it was discovered that a prototype device was undergoing trials