tbuckley/cabot-search huggingface dataset:
The value of agony aunts
Authors: P. M Boynton
Journal: BMJ (2003)

When is sex advice not sex advice? When it's sex positive information given by an agony aunt to a teenager. Then, according to the Home Office, it becomes child abuse. Well, that's how it seemed until just last week. Teenage magazines were facing possible prosecution under the Sexual Offences Bill if they discussed anything other than pregnancy or the prevention of sexually transmitted infections. Clause 15 of the bill is designed to prevent “arranging or facilitating the commission of a child sex offence,” which is suitably vague so as to leave those who offer advice on emotional aspects of sex being open to prosecution.

Fortunately, the Periodical Publishers Association (PPA) fought to get the bill amended in the House of Lords to offer exemption to those who legitimately offer advice to young people about sex. Agony aunts were granted their reprieve last week (www.ppa.co.uk/news/news.asp?news_id=602). But this was not before certain sectors of the media launched a campaign against them, and certainly not before those who offer …
Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure
Authors: Pasquale Gallo, Michael V.G. Latronico, Paolo Gallo, Serena Grimaldi, Francesco Borgia, Matilde Todaro, Philip Jones, Paola Gallinari, Raffaele De Francesco, Gennaro Ciliberto, Christian Steinkühler, Giovanni Esposito, Gianluigi Condorelli
Journal: Cardiovascular Research (2008)

AimsRecent studies have demonstrated the importance of chromatin remodelling via histone acetylation/deacetylation for the control of cardiac gene expression. Specific histone deacetylases (HDACs) can, in fact, play a positive or negative role in determining cardiac myocyte (CM) size. Here, we report on the effect on hypertrophy development of three inhibitors (HDACi) of class I HDACs.
A pruritic rash in pregnancy
Authors: R. T. Woolf, A. Abdul-Wahab
Journal: BMJ (2011)

A 33 year old woman at 40 weeks’ gestation of her first pregnancy presented with an itchy rash. This had started 14 days earlier with a few red patches on her lower abdomen but extended to involve her thighs and upper arms. The rash was increasingly pruritic. She reported gluten insensitivity (coeliac disease not confirmed) and had no dermatological or atopic history. The pregnancy had been uneventful until this point. She took no regular drugs and had not used any topical preparations. Her rash on clinical examination was as shown in the photograph.⇓





### 1 How would you describe the rash?

#### Short answer

An erythematous papular rash has spared the periumbilical region but in places has formed areas of confluent urticated erythema, especially at the striae distensae.

#### Long answer

An erythematous papular rash has spared the periumbilical region but in places has coalesced to form areas of confluent urticated erythema, especially at the striae distensae (“stretch marks”). The linear hyperpigmentation along the mid-line of the abdomen, known as the linea nigra, is a physiological phenomenon commonly seen in pregnancy.1

### 2 What is your diagnosis?

#### Short answer

A papulo-urticarial rash developing in the third trimester of a first pregnancy, originating within the striae distensae and sparing the umbilicus, is typical of polymorphic eruption of pregnancy (PEP).

#### Long answer

PEP affects about one in 160 pregnancies and commonly occurs in the third trimester (91% of cases) of primigravid women (73%).2 3 It classically presents with polymorphic erythema, papules, or vesicles (that can be urticated) that arise within the striae distensae of the abdomen and spare the peri-umbilical region, face, and acral sites.4 Less commonly the rash can become generalised, and rarely the vesicles form larger bullae.3 …
Struck-off GP admits to killing two patients without their consent
Authors: C. Dyer
Journal: BMJ (2010)

Police may reopen a murder investigation into Howard Martin, the County Durham GP acquitted of murdering three patients five years ago, after he told a newspaper reporter on Friday 18 June that he had ended the lives of two patients without their consent.

Dr Martin, 75, was struck off by the General Medical Council last week for putting 17 patients “at risk of serious harm or death” by administering large doses of painkillers “on the scantiest of evidence.” In an interview with the Daily Telegraph published after the GMC’s decision, he admitted hastening the deaths of some patients to ease their suffering, including two who had not consented to …
Blood pressure and ageing: longitudinal cohort study
Authors: J. M Starr, S. Inch, S. Cross, W. J MacLennan, I. J Deary
Journal: BMJ (1998)

tion (17/26 failed; mean assay 82%, 78% to 87%) was compounded by serious instability, with a mean loss of 17% (13% to 22%) after 4.8 months in paired samples.The figure shows the results of the paired analysis.Full data are available on request. 3
Anaemia of Uncertain Origin in Infancy
Authors: R. G. Hendrickse, M. A. R. King
Journal: BMJ (1958)

and ConclusionsThrombosis of the major pulmonary arteriis is being increasingly recognized as a complicating event in a variety of illnesses.The clinical and pathological findings are summarized in 19 further examples.In eight cases thrombosis was consequent on previous pulmonary embolism, in nine the findings suggested that autochthonous thrombosis had occurred.In two cases the pathogenesis was not established with certainty.The pathogenesis and clinical effects are briefly dis- cussed.Many of the patients have severe disease of the heart or lungs.The variability of the clinical effects attributable to pulmonary artery thrombosis is stressed.In this series they ranged from minimal changes to sudden intractable right heart failure.Although the clinical changes are often masked by the underlying illness, the diagnosis may be suggested by a history of thrombophlebitis or embolism, by the occurrence of new and unexpected clinical signs and symptoms in the course of one of the predisposing ill- nesses, and on occasion by the radiological appearances.Some patients show an illness characterized by recurrent embolization ; in others the presence of thrombotic obstruction is virtually symptomless until the on- set of acute cor pulmonale.Less frequently, the throm- bosis gives rise to a chronic cor pulmonale.Thrombosis of the major pulmonary arteries may therefore have to be considered in the diagnosis of any case of acute, subacute, or chronic cor pulmonale.I thank Dr. D. Dexter for his help and Professor T. Crawford for his assistance and advice in the preparation of the paper.
Hypothermia Therapy After Pediatric Cardiac Arrest
Authors: Dermot R. Doherty, Christopher S. Parshuram, Isabelle Gaboury, Aparna Hoskote, Jacques Lacroix, Marisa Tucci, Ari Joffe, Karen Choong, Rosemarie Farrell, Desmond J. Bohn, James S. Hutchison
Journal: Circulation (2009)

Hypothermia therapy improves mortality and functional outcome after cardiac arrest and birth asphyxia in adults and newborns. The effect of hypothermia therapy in infants and children with cardiac arrest is unknown.A 2-year, retrospective, 5-center study was conducted, and 222 patients with cardiac arrest were identified. Seventy-nine (35.6%) of these patients met eligibility criteria for the study (age >40 weeks postconception and <18 years, cardiac arrest >3 minutes in duration, survival for > or = 12 hours after return of circulation, and no birth asphyxia). Twenty-nine (36.7%) of these 79 patients received hypothermia therapy and were cooled to 33.7+/-1.3 degrees C for 20.8+/-11.9 hours. Hypothermia therapy was associated with higher mortality (P=0.009), greater duration of cardiac arrest (P=0.005), more resuscitative interventions (P<0.001), higher postresuscitation lactate levels (P<0.001), and use of extracorporeal membrane oxygenation (P<0.001). When adjustment was made for duration of cardiac arrest, use of extracorporeal membrane oxygenation, and propensity scores by use of a logistic regression model, no statistically significant differences in mortality were found (P=0.502) between patients treated with hypothermia therapy and those treated with normothermia. Also, no differences in hypothermia-related adverse events were found between groups.Hypothermia therapy was used in resuscitation scenarios that are associated with greater risk of poor outcome. In an adjusted analysis, the effectiveness of hypothermia therapy was neither supported nor refuted. A randomized controlled trial is needed to rigorously evaluate the benefits and harms of hypothermia therapy after pediatric cardiac arrest.
Atypical Pyoderma Gangrenosum in a Splenectomy Incision
Authors: Pareshkumar Patel, Arthur Topilow
Journal: New England Journal of Medicine (2002)

Figure 1. A 72-year-old woman underwent splenectomy for transfusion-dependent myelofibrosis, and rapidly advancing, nonhealing necrotic skin ulcers developed over the incision site on the eighth postoperative day (Panel A). The abdominal-wall ulcers were treated unsuccessfully with a broad-spectrum antibiotic. Multiple wound cultures remained negative for pathogens. A skin biopsy revealed neutrophilic inflammation involving the dermis. The skin was undermined by necrosis at the margins of the ulcer and showed reepithelialization (arrow in Panel B; hematoxylin and eosin, ×4). No bacteria were seen, and atypical pyoderma gangrenosum (or neutrophilic dermatosis) was diagnosed. A two-month course of oral corticosteroids, in which the . . .
G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus.
Authors: Y Obata, E Stockert, P V O'Donnell, S Okubo, H W Snyder, L J Old
Journal: The Journal of Experimental Medicine (1978)

A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia-incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen.
Rat blood neutrophils express very late antigen 4 and it mediates migration to arthritic joint and dermal inflammation.
Authors: T B Issekutz, M Miyasaka, A C Issekutz
Journal: The Journal of Experimental Medicine (1996)

Blood neutrophils contribute to joint injury in human and experimental models of arthritis. Neutrophil migration out of the blood in joint inflammation involves both the CD18 (beta2) integrins and a CD18 integrin-independent pathway. To investigate this migration, radiolabeled rat blood neutrophils were used to measure neutrophil accumulation in the inflamed joints of rats with adjuvant arthritis and the role of leukocyte integrins in migration to these joints and to dermal inflammation was determined. Neutrophils migrated rapidly (&amp;lt;2 h) to the inflamed joints 14-18 d after immunization with adjuvant. Blocking monoclonal antibodies (mAbs) to both LFA-1 and Mac-1 together, as well as a mAb to CD18, inhibited neutrophil accumulation in the inflamed joints by 50-75%. However, migration to dermal inflammation induced by C5a(des Arg)' tumor necrosis factor alpha, lipopolysaccharide, and poly-inosine:cytosine was inhibited by approximately 90%. Flow cytometry revealed the expression of low levels of very late antigen 4 (VLA-4) on nearly all rat blood neutrophils. Treatment with anti-VLA-4 plus anti-LFA-1 but neither mAb alone, strongly (60-75%) inhibited neutrophil accumulation in arthritic joints. This mAb combination also inhibited neutrophil migration to dermal inflammatory reactions by 30-70%. Blocking VLA-4 together with the CD18 integrins inhibited neutrophil accumulation by 95-99%, virtually abolishing neutrophil accumulation in cutaneous inflammation. A similar blockade of VLA-4 and CD18 decreased neutrophil accumulation in the inflamed joints by 70-83%, but a significant portion of the neutrophil accumulation to these joints still remained. In conclusion, rat blood neutrophils express functional VLA-4 that can mediate neutrophil migration to both inflamed joints and dermal inflammatory sites. VLA-4 appears to be able to substitute for LFA-1 in this migration and is particularly important for accumulation in inflamed joints. However, there exists an additional CD18- and VLA-4-independent pathway of neutrophil migration to arthritic joints that is not involved in acute dermal inflammation.
Hedgehog–GLI Signaling Inhibition Suppresses Tumor Growth in Squamous Lung Cancer
Authors: Lingling Huang, Vonn Walter, D. Neil Hayes, Mark Onaitis
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Lung squamous cell carcinoma (LSCC) currently lacks effective targeted therapies. Previous studies reported overexpression of Hedgehog (HH)–GLI signaling components in LSCC. However, they addressed neither the tumor heterogeneity nor the requirement for HH–GLI signaling. Here, we investigated the role of HH–GLI signaling in LSCC, and studied the therapeutic potential of HH–GLI suppression. Experimental Design: Gene expression datasets of two independent LSCC patient cohorts were analyzed to study the activation of HH–GLI signaling. Four human LSCC cell lines were examined for HH–GLI signaling components. Cell proliferation and apoptosis were assayed in these cells after blocking the HH–GLI pathway by lentiviral-shRNA knockdown or small-molecule inhibitors. Xenografts in immunodeficient mice were used to determine the in vivo efficacy of GLI inhibitor GANT61. Results: In both cohorts, activation of HH–GLI signaling was significantly associated with the classical subtype of LSCC. In cell lines, genetic knockdown of Smoothened (SMO) produced minor effects on cell survival, whereas GLI2 knockdown significantly reduced proliferation and induced extensive apoptosis. Consistently, the SMO inhibitor GDC-0449 resulted in limited cytotoxicity in LSCC cells, whereas the GLI inhibitor GANT61 was very effective. Importantly, GANT61 demonstrated specific in vivo antitumor activity in xenograft models of GLI+ cell lines. Conclusion: Our studies demonstrate an important role for GLI2 in LSCC, and suggest GLI inhibition as a novel and potent strategy to treat a subset of patients with LSCC. Clin Cancer Res; 20(6); 1566–75. ©2014 AACR.
Injury to Small Bowel during Criminal Abortion
Authors: A. Kouyoumdjian
Journal: BMJ (1967)

injections of Primolut Depot (17-alpha-hexanoyl- preg-4-ene 3:20-dione), 250 mg.intramuscularly once weekly.She was Rh-positive, group A.On admission her haemoglobin estimation, total, and differential white-cell counts were within normal limits.On 14 October repeat blood count showed her total W.B.C. to be 11,100 cu.mm., of which 14% were eosinophils.From 10 to 24 September she was given A.C.T.H. injections daily, but she declined treatment by corticosteroid drugs.The rash at this stage was "less troublesome"-possibly under the influence of A.C.T.H. Weekly Primolut Depot injections were continued until she left the ward on 21 October.This preg- nancy terminated at seven and a half months with a stillbirth, and on 21 July 1964 pregnancy number five was diagnosed.At that time she complained of itching feet and spots on the arms.This pregnancy also terminated spon- taneously at about 12 weeks.She was next seen here on 11 December 1964 with a three-month history of recurrence of rash, which commenced soon after she began taking Ovulen (ethynodiol acetate 1 mg.-and mestranol 0.1 mg.).The Ovulen was stopped, and one week later the rash was fading.On 30 March she recommenced taking Ovulen, and on 17 April she developed a mild itchy eruption scattered over the trunk and limbs.She resumed her course of "pills" on 26 April, and by 13 May she had an extensive eruption on the trunk and limbs, especially over the shoulder-blades.The Ovulen was again stopped, and on 14 June there were old fading lesions only and no new lesions had developed.On
Detection of fibronectin receptor in sera: Its clinical significance as a parameter of hepatic fibrosis
Authors: Masayoshi Yamauchi, Hisato Nakajima, Mitsuru Ohata, Junnichi Hirakawa, Yuji Mizuhara, Masao Nakahara, Kazuo Kimura, Kiyoshi Fujisawa, Haruo Kameda
Journal: Hepatology (1991)

Pooled sera collected from cirrhotic patients was fractionated by affinity chromatography with a fibronectin receptor monoclonal antibody against the beta-subunit of fibronectin receptor. Eluates were assayed using Western immunoblotting. The relative mobility of the protein reactive with fibronectin receptor antibody was nearly identical to that of the beta-subunit of fibronectin receptor, confirming that fibronectin receptor is present in human serum. Serum levels of the beta-subunit of fibronectin receptor were analyzed by sandwich enzyme-linked immunosorbent assay in patients with various liver diseases. The serum level of fibronectin receptor (micrograms/ml) was significantly higher in patients with chronic hepatitis (inactive, 2.59 +/- 0.04; active, 3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30), alcoholic liver disease (2.96 +/- 0.16) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Strong positive correlation was observed between serum levels of fibronectin receptor and histological findings, particularly in the degree of hepatic fibrosis. Immunohistochemical studies with fibronectin receptor antibody revealed that the beta-subunit of fibronectin receptor was present on the plasma membrane of hepatocytes and sinusoidal lining cells in the normal liver and was increased in fibrotic areas and on the plasma membrane of hepatocytes and sinusoidal lining cells of fibrotic liver. The serum level of fibronectin receptor in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.
Families are warned they can't decide treatment for incapacitated relatives
Authors: C. Dyer
Journal: BMJ (2013)

New national guidelines on the diagnosis and management of people with prolonged disorders of consciousness—vegetative state and minimally conscious state—have been issued this week by the Royal College of Physicians.1

The guidance, from a multidisciplinary group that included lawyers as well as clinicians and that had input from patients’ families, expands on the college’s 2003 working party report on the vegetative state and incorporates developments over the past 10 years.

Derick Wade, professor of neurological rehabilitation at University College London and co-chairman of the guideline group, said that the guidance was “much more” than an update of the 2003 report. “It has the potential to improve dramatically the experience of care and treatment as seen by both patients and families and also to improve significantly the outcome for patients and thus society.”

The group …
A Valedictory Editorial
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1991)

This, my last editorial as Editor-in-Chief of the Journal, offers an irresistible opportunity to reflect on what has happened at the Journal during the past 14 years and to speculate about the future.When I first took this position in 1977 I was daunted by the challenge of meeting the standards set by a long line of distinguished predecessors, beginning with John Collins Warren and ending with Franz Ingelfinger. Whether I succeeded will have to be judged by others, but I do know that I have done my best and in the process have had a unique education. Without . . .
Role of PELP1/MNAR Signaling in Ovarian Tumorigenesis
Authors: Chakravarty Dimple, Sujit S. Nair, Rajib Rajhans, Perla R. Pitcheswara, Jinsong Liu, Seetharaman Balasenthil, Xiao-Feng Le, Matthew E. Burow, Nelly Auersperg, Rajeshwar Rao Tekmal, Russell R. Broaddus, Ratna K. Vadlamudi
Journal: Cancer Research (2008)

Abstract Emerging evidence suggests that nuclear receptor (NR) coregulators have potential to act as master genes and their deregulation can promote oncogenesis. Proline-, glutamic acid–, and leucine–rich protein-1 (PELP1/MNAR) is a novel NR coregulator. Its expression is deregulated in hormone-driven cancers. However, the role of PELP1/MNAR in ovarian cancer progression remains unknown. Analysis of serial analysis of gene expression data suggested deregulation of PELP1/MNAR expression in ovarian tumors. Western analysis of PELP1/MNAR in normal and serous ovarian tumor tissues showed 3- to 4-fold higher PELP1/MNAR expression in serous tumors compared with normal ovarian tissues. To examine the significance of PELP1/MNAR in ovarian cancer progression, we have generated model cells that overexpress PELP1/MNAR and ovarian cancer cells in which PELP1/MNAR expression is down-regulated by stable expression of PELP1/MNAR-specific shRNA. Down-regulation of PELP1/MNAR in cancerous ovarian model cells (OVCAR3) resulted in reduced proliferation, affected the magnitude of c-Src and protein kinase B (AKT) signaling, and reduced tumorigenic potential of ovarian cancer cells in a nude mouse model. PELP1/MNAR overexpression in nontumorigenic immortalized surface epithelial cells (IOSE cells) promoted constitutive activation of c-Src and AKT signaling pathways and promoted anchorage-independent growth. Immunohistochemical studies using human ovarian cancer tissue arrays (n = 123) showed that PELP1/MNAR is 2- to 3-fold overexpressed in 60% of ovarian tumors, and PELP1/MNAR deregulation occurs in all different types of ovarian cancer. Collectively, these results suggest that PELP1/MNAR signaling plays a role in ovarian cancer cell proliferation and survival, and that its expression is deregulated in ovarian carcinomas. [Cancer Res 2008;68(12):4902–9]
Anti-tumoral efficacy of therapeutic human anti-KIR antibody (Lirilumab/BMS-986015/IPH2102) in a preclinical xenograft tumor model
Authors: Caroline Sola, Fabien Chanuc, Ariane Thielens, Nicolas Fuseri, Yannis Morel, Mathieu Bléry, Pascale André, Eric Vivier, Robert Graziano, Francois Romagne, Cécile Bonnafous
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Natural Killer cells (NK cells) are lymphocytes able to recognize and kill tumors for which the expression of Major Histocompatibility Complex (MHC) class I molecules is altered. This "missing self" recognition is mediated in humans by the lack of engagement of MHC class I i.e