tbuckley/cabot-search huggingface dataset:
Follow-up shows no adverse outcomes of CNEP in neonates
Authors: Susan Mayor
Journal: BMJ (2006)

Long term follow-up of a controversial trial of continuous negative extrathoracic pressure (CNEP) in newborn babies has shown no adverse outcomes, results published in the Lancet this week show (2006;367: 1080-5). The trial had resulted in an inquiry and prolonged suspension of the lead investigators.

The original study, carried out in the early 1990s, randomised newborn infants with respiratory distress syndrome to continuous negative extrathoracic pressure (pressure applied to the child's chest to help breathing) or standard treatment with supplemental oxygen or positive pressure ventilation, delivering pressurised air to the lungs. At the time, there was concern that positive pressure ventilation via an intratracheal tube might contribute to the high prevalence of chronic lung …
An Empiric Approach to the Interpretation of the Low Frequency Critically Damped Ballistocardiogram
Authors: RICHARD J. JONES, NORMAN E. GOULDER
Journal: Circulation (1950)

For the first time, the range of variation in amplitude and temporal relationships of the first four waves of the critically damped ballistocardiogram are presented for two groups of normal subjects. Characteristic deviations from this range are described in patients with vertical hearts, essential hypertension, coarctation of the aorta and aortic insufficiency. The relationship of the cardiac position to the first two patterns is reported. Explanation is found for these observations in current ballistocardiographic theory.
Generation of glycolaldehyde from guinea pig airway epithelial monolayers exposed to nitrogen dioxide and its effects on sodium pump activity.
Authors: T W Robison, H Zhou, K J Kim
Journal: Environmental Health Perspectives (1996)

Pulmonary injury from nitrogen dioxide (NO2) may in part be related to the generation of aldehydic compounds, which bind with cellular proteins and subsequently impair or inhibit cell function. We examined the generation of aldehydes from guinea pig tracheobronchial epithelial (GPTE) cell monolayers exposed to NO2. With the use of dinitrophenylhydrazine (DNP) to derivatize aldehydic compounds, glycolaldehyde, a two carbon alpha-hydroxyaldehyde, was identified in elevated levels in the basolateral fluid from monolayers exposed to NO2. DNP-glycolaldehyde levels were 81.2 +/- 2.7 and 234.0 +/- 42.6 nM in response to a 1-hr exposure to 1 and 5 ppm NO2, respectively, as compared to an air-control value of 20.3 +/- 6.8 nM. Taking into account dilution and reactivity, cellular glycolaldehyde levels could have reached as high as 3 mM for the 60-min exposure period (i.e., 0.05 mM/min). The effects of exogenous glycolaldehyde on GPTE ouabain-sensitive basolateral 86Rb uptake (an index of Na+,K(+)-ATPase activity) were examined and compared with the actions of NO2 exposure. Bolus addition of glycolaldehyde to the basolateral fluid at concentrations > or = 5 mM led to an inhibition of ouabain-sensitive 86Rb uptake, while lower concentrations had no effect. the effects of exogenous glycolaldehyde differ from NO2 exposure, which led to a sustained elevation of ouabain-sensitive 86Rb uptake with presumed generation of glycolaldehyde at a continuous low level. Glycolaldehyde does not appear to play a significant role in the acute alterations of sodium pump activity, suggesting that the NO2-induced changes in Na+,K(+)-ATPase activity of GPTE monolayers probably are further mediated by other lipid peroxidation products/oxidation processes yet to be identified.
Ruling on Physician Role in Prisoner Executions
Authors: Andrew A. Skolnick
Journal: JAMA (1994)

A COOK COUNTY Circuit Court has ordered the Illinois Medical Disciplinary Board to conduct a proper hearing of a complaint against physicians who assist in the execution of prisoners. On November 29, Judge Thomas J. O'Brien ruled that the director of the Illinois Department of Professional Regulation had no right to unilaterally dismiss a complaint filed by four Illinois physicians, Quentin Young, MD, Robert H. Kirschner, MD, William P. Gibbons, MD, and Edward A. Brunner, MD, PhD, and Physicians for Human Rights, an international humanitarian organization based in Boston, Mass. The plaintiffs are seeking to enforce professional standards that prohibit physician participation in executions (<i>JAMA</i>. 1993;269:721-723). Illinois' execution statute requires executions to be performed by lethal injection of drugs "sufficient to cause death until death is pronounced by a licensed physician according to the accepted standards of medical practice." Illinois is the only state that has enacted what the plaintiffs
Collagenase and collagenase inhibitors in osteoarthritic and normal cartilage.
Authors: M G Ehrlich, H J Mankin, H Jones, R Wright, C Crispen, G Vigliani
Journal: Journal of Clinical Investigation (1977)

In advanced osteoarthritis, all of the cartilaginous components are lost from the joint surface. Although mechanisms exist for proteoglycan degradation, there is not known to be any system for removal of the collagen. This study suggests that the loss of the collagen components may be a function of articular cartilage collagenase. The enzyme in normal human cartilage is bound to an inhibitor and appears to be present in very small amounts. Attempts to demonstrate collagenase activity in ground human articular cartilage or in its lysosomal fraction were unsuccessful. 7-Day cartilage tissue cultures also failed to demonstrate the presence of the enzyme; but the same culture fluid, incubated with trypsin, showed significant degradation of collagen, suggesting that trypsin destroyed the inhibitor. 7-Day culture fluids were then chromatographed on a heparin-charged Sepharose 4B affinity column that had been activated with cyanogen bromide. This removed the inhibitor, and the chromatographed fluid from osteoarthritic cartilage released 42% of the incorporated counts of the collagen substrate, whereas normal cartilage released 10.1% and a trypsin control, 6.4%. Electrophoresis of the degradation products of the enzyme-collagen complex incubated at 37 degrees C revealed breakdown was complete to small dialyzable fragments, while at 25 degrees C larger fragments were split off.
Treatment with alpha interferon associated with the development of paraneoplastic pemphigus
Authors: R.S KIRSNER, G.J ANHALT, F.A KERDEL
Journal: British Journal of Dermatology (1995)

The use of interferon (INF) is usually considered safe, the major side-effect being a flu-like syndrome. However, with its ability to alter immune responsiveness, INF has been associated with the induction of autoimmune diseases. We report a patient with Waldenström's macroglobulinaemia who developed a generalized blistering eruption after treatment with systemic INF-α 2A (INF) for multiple skin cancers. The patient's skin showed histological features, immunofluorescence findings, and immunoprecipitation diagnostic of paraneoplastic pemphigus. Despite aggressive treatment the patient died. In our patient, the use of INF was temporally related to the development of paraneoplastic pemphigus. Although interferon has been shown to induce other autoimmune diseases, to our knowledge this is only the second report of a patient treated with an interferon who subsequently developed a fatal autoimmune blistering disorder. Paraneoplastic pemphigus is a recently described autoimmune bullous disorder with a poor prognosis. The mechanism by which INF triggered the paraneoplastic pemphigus is not known.
CANCERS DERIVING FROM THE VIRUS PAPILLOMAS OF WILD RABBITS UNDER NATURAL CONDITIONS
Authors: John G. Kidd, Peyton Rous
Journal: The Journal of Experimental Medicine (1940)

The naturally occurring virus papillomas of western cottontail rabbits become malignant occasionally. The cancers derive from the papilloma cells, that is to say from elements already rendered neoplastic by the virus and still infected therewith. Papillomas produced with the virus in jack rabbits and snowshoe rabbits become cancerous in the same way but much more frequently, as is the case in domestic rabbits also. To all three species the virus is foreign. The character of the cancers of the wild rabbits is described and the relation of the virus to them discussed on the basis of experimental findings. The facts support the view that the cancers result from virus variation, this in many instances being but slight.
GlaxoSmithKline fires head of its China based research arm for misrepresentation of data
Authors: C. Dyer
Journal: BMJ (2013)

British pharmaceutical giant GlaxoSmithKline (GSK) has fired the head of its China based research arm and is seeking the retraction of an article in Nature Medicine after a company investigation found evidence of misrepresentation.

GSK announced the dismissal of the paper’s coauthor, neurologist Jingwu Zhang, a senior vice president and head of R&D China in Shanghai. A second author has resigned and three others are on …
THE RELATIVE PERFORMANCE CHARACTERISTICS AND CORRELATION OF THE LOGISTIC EUROSCORE AND THE SOCIETY OF THORACIC SURGERY SCORE IN THE PARTNER TRIAL
Authors: Nirat Beohar, Brian Whisenant, Ajay Kirtane, Martin Leon, Raj Makkar, Lars Svensson, D. Craig Miller, Craig Smith, Augusto Pichard, Howard Herrmann, Vinod Thourani, Todd Dewey, Michael Mack
Journal: Journal of the American College of Cardiology (2013)
Right ventricular concentric hypertrophy and left ventricular dilatation by ductal constriction in fetal rats.
Authors: K Momma, A Takao
Journal: Circulation Research (1989)

Fetal cardiac changes due to ductal constriction by maternal ingestion of nonsteroidal anti-inflammatory drugs were studied morphologically in near-term rats as an animal model, and results were compared with values of control 1 (C1, twenty-first day) and control 2 (C2, twenty-second day). The fetal ductus was constricted (-70%) (p less than 0.05) by maternal administration of 10 mg/kg indomethacin. Dilatation of the right ventricle and evidence of congestive heart failure including increased pericardial effusion (+200%) (p less than 0.05) and an increase in water content in the abdominal wall were present at 1, 4, and 8 hours after drug administration. At 24 hours after drug administration, concentric right ventricular hypertrophy was shown by a diminished right ventricular cavity (-36% vs. C2) (p less than 0.05), increased right ventricular wall thickness (+70% vs. C2) (p less than 0.05), and increased right ventricular mass (+31% vs. C1) (p less than 0.05). Left ventricular dilatation was indicated by an increased cavity volume (+87% vs. C2) (p less than 0.05) and increased muscle mass (+29% vs. C1 [p less than 0.05] or +9% vs. C2 [p greater than 0.05]). Both the wet and dry weights of the ventricles were increased. In conclusion, fetal ductal constriction caused right ventricular hypertrophy, diminished right ventricular cavity, and left ventricular dilatation and hypertrophy at 24 hours after drug administration in rats after initial congestive failure.
Different turnover rate of hepatitis C virus clearance by different treatment regimen using interferon-beta
Authors: Yasushi Shiratori, Alan S. Perelson, Leor Weinberger, Fumio Imazeki, Osamu Yokosuka, Ryo Nakata, Masashi Ihori, Katsutaro Hirota, Naomi Ono, Hisamoto Kuroda, Teiji Motojima, Masaru Nishigaki, Masao Omata
Journal: Journal of Hepatology (2000)
Application of immunocryoultramicrotomy to free cells: Ultrastructural localization of myeloperoxidase in neutrophils of human peripheral blood
Authors: Nagahito Saito, Nobuo Takemori, Katsuyuki Hirai, Noriko Kubota, Ryuichi Onodera, Masayoshi Namiki
Journal: American Journal of Hematology (1992)

Immunocryoultramicrotomy is generally considered the most suitable method for observing the immunostainings by monoclonal antibodies to intracellular antigens by electron microscopy. However, this procedure with the free cells such as peripheral blood cells or cultured cells is not widely used because of the difficulty in preparing ultrathin frozen sections. We report here a new technique for making ultrathin frozen sections of peripheral blood cells by positioning the cell in a semigelatinized medium for ultrasectioning. Monoclonal antibody against myeloperoxidase (MPO) was reacted with the ultrathin sections made with this new technique to observe the ultrastructural localization of intracellular MPO. MPO was observed in the primary granules of the neutrophils.
Netherton syndrome: report of two Taiwanese siblings with staphylococcal scalded skin syndrome and mutation of<i>SPINK</i>5
Authors: S-C. Chao, G. Richard, J.Y-Y. Lee
Journal: British Journal of Dermatology (2005)

Netherton syndrome (NS) is a severe autosomal recessive ichthyosis. It is characterized by congenital ichthyosiform erythroderma, trichorrhexis invaginata, ichthyosis linearis circumflexa, atopic diathesis and frequent bacterial infections. Pathogenic mutations in SPINK5 have recently been identified in NS. SPINK5 encodes lymphoepithelial Kazal‐type‐related inhibitor (LEKTI), a new type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. We report two Taiwanese brothers with NS. The patients had typical manifestations of NS with an atopic diathesis and recurrent staphylococcal infections, including staphylococcal scalded skin syndrome (SSSS) since birth. Horny layers were obtained by skin surface biopsy for electron microscopy from lesional skin of both patients and from normal controls. All 33 exons and flanking intron boundaries of SPINK5 were amplified for direct sequencing. The ultrastructure of the stratum corneum (SC) was characterized by premature degradation of corneodesmosomes (CDs) with separation of corneocytes. A homozygous 2260A → T (K754X) mutation of SPINK5 was found in both patients. Staphylococcal exfoliative toxin A (ETA) is a serine protease capable of cleaving desmoglein 1, an important adhesive molecule of CDs, and can cause separation of the SC, resulting in SSSS. The premature degradation of CDs found in our patients may be attributable to insufficient LEKTI, and possibly also to colonization/infection of ETA‐producing Staphylococcus aureus. Mechanisms involved in the pathogenesis of the skin barrier defect in NS are proposed. Further study is needed to prove this hypothesis.
Cassandra Still a Myth
Authors: Raymond H. Kaufman
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The commentary by Berger and Papa, in "Photodye Herpes Therapy—Cassandra Confirmed?" (238:133, 1977) adds heat rather than light to a long-standing debate. Herpes simplex viral infections of the genitalia have been directly associated with the occurrence of squamous cell carcinomas in situ of both the vulva and the penis in untreated patients.<sup>1,2</sup>A voluminous body of literature similarly implicates the untreated virus with the occurrence of carcinoma of the cervix. Laboratory evidence does indeed suggest that photoinactivated herpes virus is capable of causing cell transformation in tissue cultures. However, there is no evidence to suggest that this therapy is responsible for tumor induction in the adult human. The recent study of Friedrich et al,<sup>3</sup>on the contrary, demonstrates that photodynamic dye light therapy has not resulted in the development of epithelial atypia in a series of cases followed by biopsy up to five years after
DD-04 * PENAO: A POTENT MITOCHONDRIAL TARGETED INHIBITOR FOR GLIOBLASTOMA
Authors: S. Chung, S. Decollogne, P. Luk, H. Shen, W. Ha, B. Day, B. Stringer, P. Hogg, P. Dilda, K. McDonald
Journal: Neuro-Oncology (2014)

PENAO (4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid) is a promising new treatment for glioblastoma patients and is currently in Phase-I clinical trial testing. PENAO selectively targets cancer-specific mitochondrial metabolism by binding to the inner-mitochondrial membrane protein adenine nucleotide translocase. This results in mitochondrial membrane pore transition and reactive oxygen species (ROS)-related cell death. PENAO, as a monotherapy, has shown potent efficacy however we have recently found significant synergism with PENAO and the blocking of glutathione. In a panel of 13 glioblastoma cell lines, including both commercial and primary patient-derived lines (from both primary and recurrent tumours), PENAO demonstrated marked anti-proliferative activity with IC50 values ranging from 0.3-4.5 µM. This was up to 50 and 23-fold more specific than for normal MRC5 lung fibroblasts and astrocytes, respectively. Moreover, PENAO was 440-fold more potent than temozolomide, the frontline chemotherapeutic used clinically for glioblastoma. PENAO efficacy was recapitulated in-vivo in glioblastoma mice models. Administration of PENAO (3mg/kg/day) in mice bearing subcutaneous glioblastoma xenografts resulted in a significant inhibition of tumor size (7 partial and 3 complete responses), as well as Ki67 and TUNEL staining showing that PENAO significantly induced tumor growth arrest and death, respectively. Pharmacokinetic analysis demonstrated that PENAO readily crossed the blood-brain-barrier and accumulated specifically in tumor tissue. There were also no signs or symptoms of treatment toxicity. As PENAO induces cytotoxic ROS in glioblastoma cells, we hypothesized that inhibitors of the glutathione system would synergise with PENAO. Combining the glutathione inhibitor, sulfasalazine with PENAO, resulted in significant synergy (up to 93% increase in cell death) in all lines tested. Additionally, concomitant treatment with inhibitors of ABCC1/2 transporters and glutathione synthesis increased the efficacy of PENAO by up to 472-fold. Together these in-vitro and in-vivo models of glioblastoma show that PENAO is a highly promising new therapeutic for glioblastoma, alone or in combination with glutathione inhibition.
Hepatic Angiosarcoma Within a Small Geographic Area
Authors: William A. Smithson
Journal: JAMA (1977)

To the Editor.—  Fiechtner and Reyes recently reported (236:1704,1976) four cases of hepatic angiosarcoma occurring within 224 km of Marshfield, Wis, during the period June 1973 to November 1975. We would like to report a case of angiosarcoma involving spleen, liver, and peritoneum that was seen in January 1976 in a boy living within 426 km of Marshfield, Wis.  Report of Case.—  A 13-year-old boy was referred in August 1976. He had had an operation on July 24, 1976, for abdominal pain, and numerous tumor nodules had been found adherant to bowel, in the greater omentum, the gastrocolic ligament, and at the tail of the pancreas. The tissue was diagnosed as angiosarcoma.  The spleen had been removed in January 1976 because of traumatic rupture; on review, it was found to contain angiosarcoma.  A liver scan showed multiple tumor nodules. Lung tomograms and bone survey and scan were normal.  He was
Disruption of Aryl Hydrocarbon Receptor Homeostatic Levels during Embryonic Stem Cell Differentiation Alters Expression of Homeobox Transcription Factors that Control Cardiomyogenesis
Authors: Qin Wang, Jing Chen, Chia-I Ko, Yunxia Fan, Vinicius Carreira, Yinglei Chen, Ying Xia, Mario Medvedovic, Alvaro Puga
Journal: Environmental Health Perspectives (2013)

Background: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of xenobiotic detoxification genes and is a critical mediator of gene–environment interactions. Many AHR target genes identified by genome-wide gene expression profiling have morphogenetic functions, suggesting that AHR may play a role in embryonic development.Objectives: To characterize the developmental functions of the AHR, we studied the consequences of AHR activation by the agonist 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD), and the result of its repression by the antagonists 6,2,4-trimethoxyflavone and CH 223191 or by short-hairpin RNA (shRNA)-mediated Ahr knockdown during spontaneous differentiation of embryonic stem (ES) cells into cardiomyocytes.Methods: We generated an AHR-positive cardiomyocyte lineage differentiated from mouse ES cells that expresses puromycin resistance and enhanced green fluorescent protein (eGFP) under the control of the Cyp1a1 (cytochrome P450 1a1) promoter. We used RNA sequencing (RNA.Seq) to analyze temporal trajectories of TCDD-dependent global gene expression in these cells during differentiation.Results: Activation, inhibition, and knockdown of Ahr significantly inhibited the formation of contractile cardiomyocyte nodes. Global expression analysis of AHR-positive cells showed that activation of the AHR/TCDD axis disrupted the concerted expression of genes that regulate multiple signaling pathways involved in cardiac and neural morphogenesis and differentiation, including dozens of genes encoding homeobox transcription factors and Polycomb and trithorax group proteins.Conclusions: Disruption of AHR expression levels resulted in gene expression changes that perturbed cardiomyocyte differentiation. The main function of the AHR during development appears to be the coordination of a complex regulatory network responsible for attainment and maintenance of cardiovascular homeostasis.Citation: Wang Q, Chen J, Ko CI, Fan Y, Carreira V, Chen Y, Xia Y, Medvedovic M, Puga A. 2013. Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis. Environ Health Perspect 121:1334–1343; http://dx.doi.org/10.1289/ehp.1307297
PWE-162 Concurrent Computerised Tomography Can Optimise the Detection of Cancer in Patients Presenting with Unexplained Anaemia
Authors: J Bains, S Mansukhani, S Coates, D J Pinato, M A Mendall
Journal: Gut (2013)

<h3>Introduction</h3> Active investigation for gastrointestinal (GI) cancers is often triggered by “alarm symptoms”; features in the clinical presentation that may predict malignancy and warrant urgent referral. Unexplained anaemia (UA) is a highly prevalent presentation. The BSG guidelines recommend only upper GI endoscopy (OGD) and colonoscopy (COL). We investigated the additional diagnostic value of concurrent contrast enhanced computerised tomography of the chest, abdomen and pelvis (CT) in the investigation of patients (pts) aged &gt; 50 referred to the urgent suspected cancer (USC) pathway for GI malignancies. We evaluated its accuracy in detecting upper GI, lower GI and extraluminal malignancies in a cohort of consecutive pts presenting with and without UA. <h3>Methods</h3> We retrospectively analysed characteristics and outcomes of 350 consecutive GI USC referrals (07/2010–07/2012): 200 (Group A) presented with UA and were investigated with OGD (178, 89%), COL (70, 39%) and CT (157, 78%, with 138, 87% aged &gt; 50 years). The diagnostic outcomes were compared with a second group of 150 pts (Group B) referred with alarm symptoms (unintentional weight loss, abdominal pain, progressive dysphagia) who underwent OGD (91, 60%), COL (32, 21%) and CT (139, 93%, with 121, 89% aged &gt; 50 years). <h3>Results</h3> Group A had a mean age of 70 years (range 22–96), 51% males, mean haemoglobin (Hb) of 10.2 (5–13.8) g/dL. Pts in Group B had a mean age of 67 years (range 20–92), 60% males, mean Hb 13.9 (11.5–17.5) g/dL. Malignancy was diagnosed in 38 (19%) Group A and 17 (12%) Group B patients (p = 0.07). The proportion of malignant cases diagnosed endoscopically was not different across the studied groups (4/176, 2% and 7/86, 8% for OGD and COL in Group A; 5/91, 6% and 3/32, 9% in Group B, p = 0.3). Conversely, the rate of incident cancers identified by CT favoured Group A (33/157, 21% vs. 10/139, 7%, p &lt; 0.001), where 71% of the incident cancers were extraluminal and diagnosed in pts &gt; 50 (29/33, 87%). <h3>Conclusion</h3> Concurrent CT can optimise the detection of malignancy in pts over the age of 50 referred under the GI USC pathway, with subjects presenting with unexplained anaemia achieving the greatest diagnostic benefit. We therefore propose that CT should be incorporated within the routine investigation pathway of anaemia in the over 50s. <h3>Disclosure of Interest</h3> None Declared.