tbuckley/cabot-search huggingface dataset:
Abstract S3-2: Neoadjuvant Pertuzumab (P) and Trastuzumab (H): Antitumor and Safety Analysis of a Randomized Phase II Study ('NeoSphere')
Authors: L Gianni, T Pienkowski, Y-H Im, L Roman, L-M Tseng, M-C Liu, A Lluch-Hernandez, V Semiglazov, T Szado, G. Ross
Journal: Cancer Research (2010)

Abstract Background: P binds to HER2 and has complementary mechanisms of action with H. A clinical study of P+H showed meaningful activity in patients (pts) with metastatic HER2-positive breast cancer whose disease progressed on prior H therapy (Baselga et al. JCO 2010). NeoSphere is a Phase II randomized trial of preoperative systemic therapy comparing H and docetaxel (TH), THP, HP and TP to rank antitumor activity and tolerability. Methods: 417 pts with centrally-confirmed HER2-positive (IHC 3+ or FISH positive) breast cancer (stage II or III including locally advanced) were randomized to receive 4 cycles of TH (n=107), THP (n=107), HP (n=107), or TP (n=96) before surgery. Cycles were given intravenously q3w: P, 840 mg loading dose and 420 mg maintenance; H 8 mg/kg loading dose and 6 mg/kg maintenance; T, 75 mg/m2 with escalation to 100 mg/m2 if the starting dose was well tolerated. After surgery all pts received H to 1 year and 3 cycles of FEC; in case of neoadjuvant HP they also received T before FEC. The primary endpoint was rate of pathological complete response (pCR) in the breast. For all patients, a tissue sample at baseline, as well as at surgery following 4 cycles of neoadjuvant therapy, was collected for biomarker analyses. Results: Baseline characteristics were well balanced. About 40% of patients had locally advanced/inflammatory breast cancer. In the intent-to-treat analysis the rates of pCR and clinical objective response in the breast were: pCR for THP was significantly higher (p=0.014) than TH which was significantly higher than HP (p=0.031). Clinical disease progression was reported in 1 patient on TH and 2 patients on HP. Feasibility was good for all T-containing arms. Adverse events of grade ≥3 were rare (&amp;lt;7%) with HP in sharp contrast with the &amp;gt;50% incidence in T-containing arms. One pt developed congestive heart failure with HP. Five more patients had asymptomatic decreased LVEF with TH (1), THP (3) and TP (1) that resolved at the subsequent assessment. Biomarker analysis is ongoing. Conclusions: These data show the superior antitumor activity of THP and very favorable therapeutic ratio for HP that justify continuing study of the two monoclonals with and without docetaxel in women with HER2- positive early or metastatic breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S3-2.
Specific IgE to allergens in cord blood is associated with maternal immunity to <i>Toxoplasma gondii</i> and rubella virus
Authors: M. J. Ege, I. Herzum, G. Büchele, S. Krauss‐Etschmann, R. P. Lauener, S. Bitter, M. Roponen, S. Remes, D. A. Vuitton, J. Riedler, B. Brunekreef, J‐C. Dalphin, C. Braun‐Fahrländer, J. Pekkanen, H. Renz, E. Von Mutius
Journal: Allergy (2008)

Background: Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment. Objective: We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy. Methods: Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires ( n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers. Results: Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17–0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13–0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii . Conclusions: Maternal immunity to T. gondii and rubella may impact on atopic sensitization in the fetus. A positive T. gondii record explained the previously identified effect of prenatal farm exposure on IgE to seasonal allergens only to a minor extent.
Myocardial Edema as Detected by Pre-Contrast T1 and T2 CMR Delineates Area at Risk Associated With Acute Myocardial Infarction
Authors: Martin Ugander, Paul S. Bagi, Abiola J. Oki, Billy Chen, Li-Yueh Hsu, Anthony H. Aletras, Saurabh Shah, Andreas Greiser, Peter Kellman, Andrew E. Arai
Journal: JACC. Cardiovascular imaging (2012)
Emergency Psychiatry: Concepts, Methods, and Practices
Authors: Elissa P. Benedek
Journal: JAMA (1986)

<i>Emergency Psychiatry</i>is a work in the series<i>Critical Issues in Psychiatry</i>. The book grew out of an experimental teaching curriculum for emergency caretakers from multiple disciplines. Funding from the Division of Manpower Research and Demonstration of the National Institute of Mental Health and the collaboration of the Vermont Department of Mental Health and the ten Vermont community health centers helped in the development of the training and field testing of the model curriculum. As the curriculum developed and was implemented, new areas were added and others deleted. To complete this volume, a variety of authors were asked to contribute additional chapters. The organization of the book is superb. Everything you might want to know about emergency psychiatric care is presented briefly, succinctly, and in an easy-to-read, understandable fashion. Chapters range from emergency acute psychosis of anxious patients to care of victims of situational crisis including disaster victims, rape victims,
One hundred years of allergen immunotherapy <scp>E</scp>uropean <scp>A</scp>cademy of <scp>A</scp>llergy and <scp>C</scp>linical <scp>I</scp>mmunology celebration: review of unanswered questions
Authors: M. Calderón, V. Cardona, P. Demoly
Journal: Allergy (2012)

Abstract Allergen immunotherapy was introduced by L eonard N oon 100 years ago and is the only disease‐modifying treatment for allergic individuals. Improved understanding of immunology has taught us a great deal about the underlying mechanisms involved in allergen immunotherapy; however, despite these developments, a number of important questions remain unanswered. Several of these questions relate to the practice of allergen immunotherapy in the clinic, such as: Is it possible to unify units of allergen potency? Which treatment schedules are best? Is allergen immunotherapy effective in all patient groups? Is there a dose–response relationship for efficacy and safety?, and Is there evidence for long‐term effects following allergen immunotherapy? Others are related to new developments, such as new indications, or developments in the production of allergens. On the centenary of N oon's discovery, European experts in the field of immunotherapy met in Geneva under the aegis of the EAACI to discuss these controversial issues. This study presents outcomes and conclusions from these discussions.
Exposure on September 11, 2001, and Cancer Risk—Reply
Authors: Steven D. Stellman, Jiehui Li
Journal: JAMA (2013)

We were careful to note in our report that the short follow-up time and lack of occupational exposure data for workers such as firefighters limited our ability to fully assess cancer risks in the Registry cohort. Thus, we agree with Dr Nasseri's statement that there is still not enough information to irrefutably determine the carcinogenicity of the September 11 terrorist attack.
Case of Medullary Sarcoma of the Prostate Gland, in a Child Aged Nine Months
Authors: C. R. Bree
Journal: BMJ (1846)

On the othter liand, Dr. Ashwell remnarks that "it would liae been as well if these (placental) orifices and t,eir capakcities had been demonstrated.I hiav never yet seen them, A4ough I have subjected
Controlled oxygen therapy and pulmonary heart failure
Authors: A. C. Ude, P. Howard
Journal: Thorax (1971)

One hundred and sixty-six episodes of pulmonary heart failure were treated in 40 patients with chronic bronchitis. The natural history of the disease is described when controlled oxygen is the principal therapy. Only eight episodes of heart failure required intermittent positive pressure ventilation. Despite careful attention to the details of the controlled oxygen technique the longterm survival of these patients was no better than during an earlier period when oxygen was either not given or administered intermittently for short periods. The implications of this finding are discussed.
Diastolic Pressure in Type 2 Diabetes
Authors: Etty Osher, Naftali Stern
Journal: Diabetes Care (2008)

The practicality of vigorous lowering of systolic pressure in diabetes to &amp;lt;130 mmHg remains uncertain. Baseline blood pressure data from several recent trials indicate that, in diabetic subjects, there is nearly a fourfold excess in systolic pressure (the difference between baseline pressure and target pressure) over diastolic pressure with respect to the recommended systolic/diastolic target pressure of &amp;lt;130/80 mmHg. Additionally, systolic pressure was 2–3 mmHg higher and diastolic pressure was 1–3 mmHg lower in diabetic hypertensive than in nondiabetic hypertensive individuals, which adds ∼4 mmHg to pulse pressure and also to the difference between the excess systolic and excess diastolic pressure. We attempted to force (titrate both systolic and excess diastolic pressure) systolic and diastolic blood pressure to &amp;lt;130/85 mmHg based on Joint National Committee VI guidelines in the setting of a clinical practice in 257 diabetic patients. Although target systolic pressure was attained in a third of this cohort, in 57% of the patients, the attained diastolic pressure was ≤70 mmHg. Patients with final diastolic pressure &amp;lt;70 mmHg were older, had a higher prevalence of coronary artery disease, and had higher initial systolic and pulse pressures. Review of achieved blood pressure in studies such as the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicates that a significant fraction of the diabetic subjects’ diastolic pressure was also driven down to &amp;lt;70 mmHg or even &amp;lt;60 mmHg. Thus, attempted lowering of blood pressure to target systolic pressure is associated with inordinate lowering of diastolic pressure in a significant number of patients. Whether the benefits of tight systolic control to &amp;lt;130 mmHg outweigh the risks of excessive diastolic reduction, especially in older diabetic subjects or diabetic patients with coronary artery disease, remains unresolved.
Diseases of the Liver, vols 1 &amp;amp; 2
Authors: Frank L. Iber
Journal: JAMA (1994)

This established book, now in its seventh edition and 39th year, is a clear landmark for clinicians. Compared with the previous, 1987, edition, the book is 5% longer, has some 15% new authors, and features a great quantity of new illustrations. The organization is about the same, with some chapters markedly truncated or even appropriately dropped and others expanded, reflecting the changing emphasis of our field.  Many of the chapters are new or rewritten. Bilirubin metabolism adds a wealth of new information to an area that I thought I understood. Endoscopy in the management of hepatobiliary disease is wonderfully illustrated, sclerosing cholangitis has been elevated to a fine chapter, there is an excellent chapter on the disposition and elimination of drugs by the liver and a solid chapter on the porphyrias. Chapters also deal with the liver in the acquired immunodeficiency syndrome (AIDS) and following total parenteral nutrition.  Chapters from
Autonomic Neuropathy and Inappropriate Secretion of Antidiuretic Hormone Occurrence in a Patient With Bronchogenic Carcinoma
Authors: David L. Carr-Locke
Journal: JAMA (1979)

WHILE the syndrome of inappropriate secretion of antidiuretic hormone is a well-recognized complication of bronchogenic carcinoma,<sup>1</sup>its combination with autonomic dysfunction seems much less common.<sup>2,3</sup>There appears to be only one previous report describing a patient in whom loss of sweating, hypotension, and nonobstructive urinary retention were noticed.<sup>4</sup>Another report describes this combination with a pancreatic carcinoma.<sup>5</sup> A patient with the combined effects of autonomic neuropathy and hyponatremia had metastatic bronchogenic carcinoma. <h3>Report of a Case</h3> A 65-year-old man had a one-year history of severe constipation, 6-kg weight loss, impotence, and two episodes of collapse in which he had lost consciousness. Examination, sigmoidoscopy, barium enema examination, and chest roentgenograms were normal, but the serum sodium level was 120 mEq/L. One month later he was admitted as an emergency with attacks of feeling distant in which he could not speak and other episodes in which he lost
Tubularized Incised Plate Urethroplasty for Distal and Mid&amp;ndash;Penile Hypospadias
Authors: Murat Dayan&ccedil;, M. &Ouml;zg&uuml;r Tan, Adil G&ouml;kalp, Ibrahim Y&inodot;ld&inodot;r&inodot;m, Ahmet Fuat Peker
Journal: European Urology (2000)
How Well Designed Is the Human Lung?
Authors: John B. West
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Although it is often stated that the structure of the human lung is ideally suited to its gas exchange function, the lung is very vulnerable under some abnormal conditions. One example is the postoperative period in a patient with an otherwise normal lung where retained secretions can rapidly cause unventilated areas or atelectasis and substantial impairment of gas exchange. Some pulmonologists may be surprised to learn that evolution has provided a very different, and arguably superior, lung design in the bird. Here, the gas exchange and ventilatory functions of the lung are separated. Gas exchange occurs in relatively rigid parabronchi, which are more robust than the delicate alveoli in the human lung, and ventilation is performed by highly expandable air sacs. A comparison of these two completely divergent evolutionary paths throws light on some of the problems of the human lung.

Suppose you were asked to design* a heat exchanger, such as the radiator of a car. The purpose of this is to enable heat from the engine to be eliminated to the outside air. One way would be to pump the hot coolant fluid from the engine through a grid of many small tubes and have air passed across these by means of a fan. In fact, this is the time-honored design for car radiators. If you suggested this, Henry Ford would have been proud of you.

But you might come up with an alternative design in which the small tubes containing the coolant fluid were enclosed in a bellows that was alternately inflated and deflated so that the air in the bellows was heated and then expelled. In fact, you might even conceive of a design in which the small tubes themselves were part of the bellows. A critic might say that this alternative design was unnecessarily complicated and prone to problems, especially if the small tubes formed part of the moving bellows. But amazingly this is the design that evolution chose for the mammalian, and therefore human, lung.

The lung is a gas exchanger, which is closely analogous to a heat exchanger. Although in the latter, heat is taken from the engine and eliminated into the surrounding air, the lung does this for carbon dioxide, and at the same time it takes up oxygen.

The route taken by evolution for the mammalian lung is even more astonishing when we realize that a completely different path was pursued in designing the bird lung. Indeed, the bird has a lung rather like the classic car radiator. A comparison of these two quite divergent evolutionary paths helps us to understand some of the vulnerabilities of the human lung.
Citizen jury should consider aspirin prophylaxis
Authors: Rachel T Iredale
Journal: BMJ (2005)

Drug combinations and all cause mortality in heart disease No new insights were gainedEditor-Hippisley-Cox and Coupland conclude that the addition of angiotensin converting enzyme (ACE) inhibitors to combinations of drugs conferred no additional benefit in their study of patients in primary care with ischaemic heart disease. 1 However, such a conclusion should be reached with caution.The drugs were given to the patients with the highest risk of death.A higher percentage of patients who died were treated with ACE inhibitors, and the greatest improvement in risk of death after adjustment for risk factors was seen in the patients treated with these drugs.ACE inhibitors might thus have been given to the patients with the most severe disease in each comorbidity group-for example, to diabetic patients with kidney disease and to patients with the most severe heart failure.Therefore the study can give no indication of the crucial question whether the outcome would have been equally good for the group of 463 patients who probably had the most severe disease and received statins, aspirin, blockers, and ACE inhibitors if they had not been given ACE inhibitors.Replacement of yes or no for comorbidity factors with more discriminating variables, such as presence of microalbuminuria and a severity measure for heart disease, would probably have improved the study.However, this cannot replace the quality of a randomised, placebo controlled study comparing the effect of adding ACE inhibitors to the other study drugs.Therefore the study by Hippisley-Cox and Coupland adds no new knowledge to how patients with ischaemic heart disease in primary care should be treated.
Hydraulic estimation of stenotic orifice area: a correction of the Gorlin formula.
Authors: S R Cannon, K L Richards, M Crawford
Journal: Circulation (1985)

To determine the source of errors in the Gorlin formula for estimating stenotic valvular orifice area, we used a pulsatile flow model that emulated left ventricular and aortic pressures and flow and allowed control of ventricular outflow orifice area. After comparing orifice areas calculated by the Gorlin formula with actual orifice areas, the Gorlin formula constant (k) was found to be highly correlated with the square root of the mean transvalvular gradient (r = .95). A new formula was derived empirically and predicted areas more accurately and with smaller standard errors than the Gorlin formula in the model (r = .98, SEE = 0.11 and r = .87, SEE = 0.28, respectively) in a series of 19 patients with Hancock porcine xenograft valves (r = .89, SEE = 0.07 and r = .60, SEE = 0.12, respectively) and in the original series of patients reported by Gorlin and Gorlin in proposing the Gorlin formula (r = .93, SEE = 0.11 and r = .91, SEE = 0.12, respectively).
Involucrin expression in keratinization disorders of the skin—a preliminary study
Authors: J. KANITAKIS, G. ZAMBRUNO, J. VIAC, J. THIVOLET
Journal: British Journal of Dermatology (1987)

We have studied the expression of involucrin in a variety of keratinization disorders, mostly of genetic origin using an avidin-biotin-peroxidase technique. In normal human epidermis 25% of the living epidermis was labelled. The diseases studied fell into two groups. Diseases with greatly increased involucrin staining including collodion baby (38%), Darier's disease (49%), Flegel's disease (56%), erythrokeratoderma variabilis (60%), epidermal naevus with epidermolytic hyperkeratosis (45%) and congenital bullous (58%) and non-bullous (44%) ichythyosiform erythroderma; and diseases with normal or slightly increased staining, including ichthyosis vulgaris (27%), X-linked ichthyosis (25%), confluent and reticulate papillomatosis (27%) and simple epidermal naevus (28%). These results demonstrate that involucrin expression is altered in some keratinization disorders and suggest that in such conditions cellular functions other than keratin metabolism are also affected.
The Albert Lasker Medical Awards. Role of the cyclic AMP-dependent protein kinase in signal transduction
Authors: E. G. Krebs
Journal: JAMA (1989)

The first example of an enzyme that undergoes phosphorylation and dephosphorylation was phosphorylase, which catalyzes the initial step in the breakdown of tissue glycogen, a process that occurs when cells are stimulated by certain hormones. The phosphorylation reaction that activates phosphorylase is catalyzed by an enzyme designated "phosphorylase kinase," whereas the dephosphorylation reaction is catalyzed by an enzyme called "phosphorylase phosphatase." Phosphorylase kinase, like phosphorylase itself, is regulated by phosphorylation-dephosphorylation. In this instance the enzyme is phosphorylated and activated by a protein kinase that is the intracellular target of adenosine 3',5'-cyclic phosphate, the second messenger of hormone action that was discovered by the late Earl Sutherland. Knowledge of these steps led to the establishment of the glycogenolytic cascade in which adenosine 3',5'-cyclic phosphate, formed as a result of hormone action, first activates the adenosine 3',5'-cyclic phosphate-dependent protein kinase, which in turn activates phosphorylase kinase, which then converts inactive phosphorylase to its active form. This is followed by the breakdown of glycogen.
Objective vs. subjective factors in the psychological impact of vitiligo: the experience from a French referral centre
Authors: P. Kostopoulou, T. Jouary, B. Quintard, K. Ezzedine, S. Marques, S. Boutchnei, A. Taieb
Journal: British Journal of Dermatology (2009)

Journal Article Objective vs. subjective factors in the psychological impact of vitiligo: the experience from a French referral centre Get access P. Kostopoulou, P. Kostopoulou Centre de Référence des Maladies Rares de la Peau, Service de Dermatologie, Hôpital Saint André, 33075 Bordeaux, FranceLaboratoire de Psychologie EA4139, Université Bordeaux 2, Bordeaux, France Search for other works by this author on: Oxford Academic Google Scholar T. Jouary, T. Jouary Centre de Référence des Maladies Rares de la Peau, Service de Dermatologie, Hôpital Saint André, 33075 Bordeaux, France Correspondence: Thomas Jouary. E‐mail: thomas.jouary@chu‐bordeaux.fr Search for other works by this author on: Oxford Academic Google Scholar B. Quintard, B. Quintard Laboratoire de Psychologie EA4139, Université Bordeaux 2, Bordeaux, France Search for other works by this author on: Oxford Academic Google Scholar K. Ezzedine, K. Ezzedine Centre de Référence des Maladies Rares de la Peau, Service de Dermatologie, Hôpital Saint André, 33075 Bordeaux, France Search for other works by this author on: Oxford Academic Google Scholar S. Marques, S. Marques Centre de Référence des Maladies Rares de la Peau, Service de Dermatologie, Hôpital Saint André, 33075 Bordeaux, France Search for other works by this author on: Oxford Academic Google Scholar S. Boutchnei, S. Boutchnei Centre de Référence des Maladies Rares de la Peau, Service de Dermatologie, Hôpital Saint André, 33075 Bordeaux, France Search for other works by this author on: Oxford Academic Google Scholar A. Taieb A. Taieb Centre de Référence des Maladies Rares de la Peau, Service de Dermatologie, Hôpital Saint André, 33075 Bordeaux, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 1, 1 July 2009, Pages 128–133, https://doi.org/10.1111/j.1365-2133.2009.09077.x Published: 01 July 2009