tbuckley/cabot-search huggingface dataset:
Consultant suspended for not getting consent for cardiac procedure
Authors: C. Dyer
Journal: BMJ (1998)

An 18 year old para1+0 was referred to our fetal medicine unit with an intraoral cystic structure (22mm×19mm) detected at routine anomaly scan. Fetal MRI confirmed a large thin walled cyst (25mm×24mm×18mm) in the midline filling the entire oral cavity and inseparable from the tongue. Differential diagnosis included congenital ranula, epidermoid cyst, unilocular lymphatic malformation and enteric duplication cyst. Multidisciplinary team counselling was performed involving fetal medicine specialists, neonatologists, paediatric ENT surgeons and paediatric anaesthetists and a management plan formulated. Ultrasound monitoring through the course of the pregnancy revealed no significant change in the size of the cyst. Development of polyhydramnios suggested that the cyst was beginning to interfere with fetal swallowing raising the possibility of potential problems with securing and maintaining airway at delivery. Hence delivery was arranged by elective caesarean section at 38+ weeks under steroid cover. Operation On Placental Support (OOPS) procedure was done at the time of delivery with the cyst being decompressed and intubation done while placental circulation was maintained. Excision of the lesion was performed on day 2 and histology confirmed a thyroglossal duct cyst. The baby did well in the neonatal period and was discharged home in the first week of life. With this case report we seek to highlight management of this extremely rare congenital cystic malformation of the oral cavity and the crucial role of combined imaging and multidisciplinary input to ensure a good outcome.
Denial and Silent Ischemia: Which Comes First?
Authors: P. Janne
Journal: JAMA (1991)

<h3>To the Editor. —</h3> In a Special Communication of September 5 about silent myocardial ischemia, Barsky et al<sup>1</sup>emphasize the importance of the person in the so-called silent ischemia syndrome. They summarize interesting previous findings about symptom perception, appraisal, and reporting that can be taken into account to explain the absence of anginal symptoms in these patients. However, they state that "a link between denial and silent ischemia is yet to be established." Actually, it has been. We published empirical evidence supporting the hypothesis of such an "undercomplaining behaviour pattern" in silent myocardial ischemia.<sup>2</sup>Our answer to the question "What is actually silent in asymptomatic coronary artery disease, the patient himself or the ischemia?" was that patients with silent myocardial ischemia deny not only pain but also sickness, illness seriousness, and even the presence of a cardiac disease. Confirmatory data were published in a second study,<sup>3</sup>which
Pediatric Anxiety — Underrecognized and Undertreated
Authors: Graham J. Emslie
Journal: New England Journal of Medicine (2008)

Generalized anxiety disorder, separation anxiety disorder, and social phobia are relatively prevalent disorders that affect 6 to 20% of children and adolescents.1 However, these disorders frequently go unrecognized by medical professionals. This is a critical problem, since a younger age of onset and severity of illness result in poor outcomes in adolescents and adults. Furthermore, the failure to identify these disorders early in life leads to increased rates of anxiety disorders, depression, and substance abuse later in life, as well as to educational underachievement.2 In this issue of the Journal, the report by Walkup et al. on the Child–Adolescent Anxiety . . .
Activation of Epithelial Cells and Lymphocytes by Staphylococcal Enterotoxin B Induces Profound Expression of Inflammatory Cytokines and Chemokines
Authors: D.A. Wagner, S.C. Shin, B.P. Tancowny, R.P. Schleimer, L.C. Grammer
Journal: Journal of Allergy and Clinical Immunology (2006)
Deciphering Genetic Disease in the Genomic Era: The Model of GnRH Deficiency
Authors: Gerasimos P. Sykiotis, Nelly Pitteloud, Stephanie B. Seminara, Ursula B. Kaiser, William F. Crowley
Journal: Science Translational Medicine (2010)

Recent technical and conceptual advances presage the elucidation of the genetic causes of human disease through unbiased, patient-oriented investigations.
Abstract IA14: Functional genomics to identify cancer targets and resistance
Authors: William C. Hahn
Journal: Clinical Cancer Research (2012)

Abstract Recent advances in genomics now make it possible to consider enumerating all of the genetic lesions in specific cancers. While these approaches will yield critical information regarding the identity, number, and types of alterations found in human tumors, a complementary approach to decipher the molecular basis of malignant transformation depends upon the application of genome scale tools to annotate the function of genes involved in cancer initiation and progression. Over the past several years, we have developed genome scale RNAi libraries and open reading frame expression libraries that permit a systematic evaluation of genes involved in cancer initiation and maintenance. Using these libraries, we have now performed screens in a panel of human cancer cell lines to systematically identify cancer vulnerabilities. By combining these functional approaches with information derived from mapping the structural abnormalities present in cancer genomes, we have identified several new oncogenes that contribute to cancer development. In pilot studies, we have identified several genes that act as synthetic lethal partners to known oncogenes or mediate resistance to targeted therapies. In recent work, we have expanded the scale of these experiments to genome scale in more than 100 cell lines, which has permitted greater expansion and deeper investigation into genes that program the malignant state. Together, these studies suggest that combining forward and reverse genetic approaches with information derived from the cancer genome characterization projects will yield a comprehensive list of cancer vulnerabilities and establish a general approach for the rational identification of oncogenic and codependent pathways in cancer.
The influence of molecular form of local anesthetic-type antiarrhythmic agents on reduction of the maximum upstroke velocity of canine cardiac Purkinje fibers.
Authors: G A Gintant, B F Hoffman, R E Naylor
Journal: Circulation Research (1983)

We studied the local anesthetic effects of the quaternary lidocaine analogues QX-314, QX-572, and QX-222, the tertiary amine lidocaine, its analogues tocainide, 6603, 6211, and the neutral local anesthetic benzocaine to determine if molecular charge of antiarrhythmic agents influences their local anesthetic effects on heart fibers. We used standard microelectrode techniques and canine cardiac Purkinje fibers to compare the effects of stimulation rate, drug concentration, and K+-induced changes in resting membrane potential on the reduction of fast inward sodium current using the maximum rate of rise of the action potential upstroke, Vmax, as an index of changes in peak sodium current. Use-dependent block, defined as a modulation of the reduction in Vmax by local anesthetics due to changes in the stimulation rate, was observed with the permanently charged analogues and was most prominent for agents existing predominantly in the charged form, but was absent for the neutral local anesthetic benzocaine. The development of use-dependent block during rapid stimulation preceded by prolonged periods of quiescence was an exponential process which became more rapid with increasing drug concentration. Recovery from use-dependent block during quiescence was an exponential process that was not influenced by similar drug concentration changes. All local anesthetics caused tonic block, defined as a drug-induced reduction of Vmax from control that attained a constant value at slow stimulation rates (cycle length range 15 seconds to 2 minutes) and was not changed by prolonged (up to 8 minutes) periods of quiescence. These findings suggest that the charged form of lidocaine and its analogues is responsible for use-dependent block of cardiac sodium channels.
Intensive Diagnostic Follow-up After Treatment of Primary Breast Cancer
Authors: Marco Rosselli Del Turco
Journal: JAMA (1994)

Objective.  —To evaluate the effectiveness of early detection of intrathoracic and bone metastases in reducing mortality in breast cancer patients.  Design.  —Randomized clinical trial allocating breast cancer patients to two alternative follow-up protocols (intensive vs clinical) for at least 5 years.  Setting.  —Twelve breast clinics (referral centers) in different areas in Italy.  Patients.  —A total of 1243 consecutive patients (either premenopausal or postmenopausal) surgically treated for unilateral invasive breast carcinoma with no evidence of metastases. The two study groups were well balanced in terms of clinical and prognostic characteristics.  Intervention.  —Patients in both treatment groups had physical examination and mammography, while patients of the intensive follow-up group had, in addition, chest roentgenography and bone scan every 6 months.  Main Outcome Measures.  —Vital status at 5 years was the main outcome; information was available for all except five patients (0.4%). Relapse-free survival was also analyzed.  Results.  —Overall, 393 recurrences (104 local and 289 distant) were observed during the study. Increased detection of isolated intrathoracic and bone metastases was evident in the intensive follow-up group compared with the clinical follow-up group (112 vs 71 cases), while no difference was observed for other sites and for local and/or regional recurrences. The 5-year relapse-free survival rate was significantly higher for the clinical follow-up group, with patients in the intensive follow-up group showing earlier detection of recurrences. No difference in 5-year overall mortality (18.6% vs 19.5%) was observed between the two follow-up groups.  Conclusions.  —Periodic chest roentgenography and bone scan allow earlier detection of distant metastases, but anticipated diagnosis appears to be the only effect of intensive follow-up, and no impact on prognosis is evident after 5 years. Periodic intensive follow-up with chest roentgenography and bone scan should not be recommended as a routine policy.  (JAMA. 1994;271:1593-1597)
CEREBROSIDE SYNTHESIS IN GAUCHER'S DISEASE *
Authors: Eberhard G. Trams, Roscoe O. Brady
Journal: Journal of Clinical Investigation (1960)

Familial lipodystrophic conditions, such as Gaucher's, Niemann-Pick, and Tay-Sachs dis- ease, are characterized by the intracellular ac- cumulation of abnormally large quantities of sphingolipids.In Gaucher's disease, the offend- ing lipids are cerebrosides, while Niemann-Pick and Tay-Sachs diseases are characterized by the accumulation of sphingomyelin and gangliosides, respectively.In Gaucher's and Niemann-Pick disease, involvement of the reticuloendothelial sys- tem is extensive, and splenomegaly and hepato- megaly are frequently observed.Lieb in 1924 ( 1 ) identified the lipid stored in reticuloendothelial cells in a case of Gaucher's disease as a cerebro- side.His findings were supported by other in- vestigators (2, 3), and eventually Halliday, Deuel, Tragerman and Ward (4) and Rosenberg and Chargaff (5) presented evidence that the ac- cumulated cerebrosides in Gaucher's disease con- tained predominantly glucose instead of the high content of galactose usually present in cerebrosides.It was felt that techniques developed in this laboratory for studies of the biosynthesis of sphingosine and cerebrosides might be useful for investigations of cerebroside formation in tissue samples obtained from patients with Gaucher's disease.The data obtained by Brady and Koval (6), Burton, Sodd and Brady (7), and Cleland and Kennedy (8) indicate that cerebroside syn- thesis probably occurs in the following fashion: palmitic aldehyde + serine --sphingosine + C02; sphingosine + uridinediphosphate galactose -> psychosine + uridinediphosphate; psychosine + fatty acid -* cerebroside.Since purified enzyme systems which catalyze the biosynthesis of cere- brosides were not available, tissue slices were em- ployed in the present investigations to study the formation of these sphingolipids.Tissue was oc- casionally available from patients who were sple-
Abstract 1069: The role of mammalian Ecdysoneless in cell cycle regulation and cancer
Authors: Channabasavaiah B. Gurumurthy, Jun H. Kim, Xiangshan Zhao, Mayumi Naramura, Hamid Band, Vimla Band
Journal: Cancer Research (2010)

Abstract Our long term research goal is to understand biochemical mechanisms of immortalization of human mammary epithelial cells (hMECs) that represents an early step in breast cancer progression. We have generated several hMEC immortalization models using viral oncogenes, mutated cancer genes as well as radiation treatment of cells. In one of such immortalization model, we identified Ecdysoneless (Ecd) protein as the human papilloma virus (HPV) E6 interacting protein. We have reported earlier that HPV16 E6 protein is highly efficient for hMEC immortalization. Here, we present evidence that Ecd, an evolutionarily conserved protein, is a novel regulator of the Rb/E2F pathway. We generated a conditional Ecd knockout mouse model and observed that complete deletion of Ecd leads to early embryonic lethality in mice. The experiments using conditional Ecd-null MEFs created from Ecdlox/lox revealed that lack of Ecd inhibits cellular proliferation by delaying G1-S cell cycle progression and down-regulates E2F target gene expression. Furthermore, Ecd directly binds to Rb at the pocket domain and disrupts the interaction of Rb with E2F, leading to impairment of repressive effect of Rb on E2F target promoters. Thus, we demonstrate that Ecd is an essential protein in embryonic development and a novel regulator of G1-S cell cycle transition by modulating Rb/E2F pathway. Consistent with these observations, overexpression of Ecd in hMECs hastens the exit of cells from G1 phase of the cell cycle. Significantly, immunohistochemical analyses showed Ecd is overexessed in ductal carcinoma in situ as well as in infiltrating ductal carcinoma of breast. In conclusion, Ecd plays an important role in cell cycle progression and its deregulation can lead to abnormal cell proliferation leading to breast cancer progression. 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 1069.
<i>all‐trans</i>‐Retinoic acid‐induced expression and regulation of retinoic acid 4‐hydroxylase (CYP26) in human promyelocytic leukemia
Authors: Bulent Ozpolat, Kapil Mehta, Ana M. Tari, Gabriel Lopez‐Berestein
Journal: American Journal of Hematology (2002)

Abstract all‐trans ‐Retinoic acid (ATRA) induces complete remission in majority of patients with acute promyelocytic leukemia (APL). However, accelerated metabolism of ATRA that is induced by chronic daily administration of oral ATRA has been implicated as one of the mechanisms leading to a reduced sensitivity or resistance to ATRA therapy. We investigated the expression and regulation of CYP26, a novel p450 enzyme, which is highly specific for ATRA, in promyelocytic leukemia cells (NB4 and HL‐60). We found that treatment of NB4 cells with a pharmacological concentration of ATRA (1 μM) induced rapid and dose‐dependent expression of CYP26 mRNA. The CYP26 expression returned to pretreatment levels in both cells after ATRA was removed from the media. Retinoic acid receptor‐alpha (RARα) specific antagonist (CD2503) totally abolished the ATRA‐induced expression of CYP26 mRNA in HL‐60 and NB4 cells. Furthermore, HL‐60R, a HL‐60 subclone expressing nonfunctional RAR because of a point mutation in the ligand‐binding domain of RARα, failed to show CYP26 mRNA expression in response to ATRA. ATRA‐induced expression of CYP26 was restored in HL‐60R cells retrovirally transduced with RARα, but not in those cells transduced with the other retinoid receptors. In conclusion, ATRA induces expression of CYP26 in myeloid and promyelocytic leukemia cells and this expression is modulated by RARα. The induction of CYP26 expression by ATRA treatment might be related to a substrate‐driven feedback mechanism to regulate intracellular concentrations of ATRA and its over expression in some clones may be partly responsible for reduced sensitivity or resistance to ATRA therapy. Am. J. Hematol. 70:39–47, 2002. © 2002 Wiley‐Liss, Inc.
Atrial Heart Sounds in Atrial Fibrillation and Fluttter
Authors: LEWIS M. NEPORENT
Journal: Circulation (1964)

Audible atrial contractions were recorded in a case of rheumatic heart disease during atrial fibrillation and the transition stage to atrial flutter. With coarse atrial fibrillation these correlated only roughly with the electrocardiogram, and appeared to have a regularity not always apparent on the electrocardiogram. In atrial flutter, the atrial contraction sounds were synchronous with the "f" waves. The intensity, quality, and occurrence of the atrial sounds during ventricular systole suggest an extracardiac origin.
A descriptive and prognostic study of systemic sclerosis-associated myopathies
Authors: B Ranque, F-J Authier, V Le-Guern, C Pagnoux, A Berezne, Y Allanore, D Launay, E Hachulla, A Kahan, J Cabane, R Gherardi, L Guillevin, L Mouthon
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: To describe the clinical characteristics and muscle pathological features of patients with systemic sclerosis (SSc) and myopathy and analyse their impact on muscle outcome. Methods: Thirty-five patients with myopathy and available muscle biopsy were restrospectively investigated from the charts of four hospital centres. Results: Twenty-six (74%) cases had diffuse SSc. The median time from SSc diagnosis was 5 years (range 0–23) at myopathy onset. The main myopathological features were mononuclear inflammation (63%), muscle atrophy (60%), necrosis (59%), regeneration (44%), fibrosis (24%) or microangiopathy (27%). After a median follow-up of 4.4 years, 24 patients (69%) showed complete or partial muscle remission. Only histological muscle inflammation was associated with good muscle prognosis in multivariate analysis (odds ratio 44.7, 95% CI 2.8 to 704.7). Patients without muscle inflammation had a poor response to corticosteroids (38% favourable response vs 90% in patients with inflammation). Conclusion: Muscle histopathology is critical in the therapeutic management of SSc-associated myopathy.
Depression, Alexithymia and Long-Term Mortality in Chronic Hemodialysis Patients
Authors: Masayo Kojima, Junichiro Hayano, Sadao Suzuki, Hachiro Seno, Hirotake Kasuga, Hiroshi Takahashi, Takanobu Toriyama, Hirohisa Kawahara, Toshiaki A. Furukawa
Journal: Psychotherapy and Psychosomatics (2010)

&lt;i&gt;Background:&lt;/i&gt; Depression increases the risk of mortality in hemodialysis patients. Alexithymia, a disorder of affect regulation, has also been reported to be associated with mortality risk in the general population. We conducted a prospective study to estimate the independent impact of depression and alexithymia on long-term mortality. &lt;i&gt;Methods:&lt;/i&gt; A total of 230 hemodialysis outpatients, with a mean age of 56.3 ± 9.6 years, completed a batch of self-report measures including the Beck Depression Inventory-II (BDI-II), the 20-item Toronto Alexithymia Scale (TAS-20) and the 36-item Short Form Health Survey (SF-36). Survival status was confirmed every 6 months for up to 5 years. The presence of depression and alexithymia was defined by a BDI-II score of ≧14 and a TAS-20 score of ≧61, respectively. &lt;i&gt;Results:&lt;/i&gt; During the follow-up period, 27 deaths were confirmed. Both depression and alexithymia were associated with an increased risk for all-cause mortality; the age- and sex-adjusted hazard ratio for depression was 2.36 (95% CI: 1.08–5.15; p = 0.03) and that for alexithymia was 4.29 (95% CI: 1.95–9.42; p &lt; 0.001). Depression lost its statistical significance after controlling for alexithymia, whereas alexithymia remained significant even after adjusting for the baseline depression, health status (the summary scores of the SF-36), marital status and clinical covariates (multivariate adjusted hazard ratio = 3.62; 95% CI: 1.32–9.93; p = 0.01). &lt;i&gt;Conclusions:&lt;/i&gt; Alexithymia is a strong independent risk factor for all-cause mortality in hemodialysis patients.
Altered Biodistribution of Bone Seeking Agents in the Presence of Iron-overload
Authors: María del Sol Pérez-Lago, M C. De Vírgala, R Siurana, M J. Ferrando, M Danús, V Izquierdo, A Pujol
Journal: Clinical Nuclear Medicine (2004)

It is well-known that biodistribution of radiopharmaceuticals in vivo can be altered by different mechanisms, but only a few examples of this have been published. A 72-year-old woman was seen with atrial fibrillation and ultrasonographic features of restrictive cardiomyopathy. She was suspected to have amyloidosis and scintigraphy with Tc-99m pyrophosphate was performed. Curiously, the obtained images showed increased renal activity and blood pool was labeled, but myocardial and bony uptake were not detected. A bone scan with Tc-99m hydroxyphosphonate confirmed our findings. The responsible agent for this phenomenon was a significant iron overload, which we discovered on reviewing the woman's clinical history.
Cytomegalovirus esophagitis preceding the diagnosis of systemic lupus erythematosus
Authors: R. Kellermayer, S. Kim, M. Perez, N. Tatevian, M. Dishop, S. Abrams, S. Kitagawa, M. Gilger
Journal: Endoscopy (2007)

Corrected by: Cytomegalovirus esophagitis preceding the diagnosis of systemic lupus erythematosusEndoscopy 2007; 39(S 1): E239-E239DOI: 10.1055/s-2007-966807
EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors
Authors: Young Lim Choi, Manabu Soda, Yoshihiro Yamashita, Toshihide Ueno, Junpei Takashima, Takahiro Nakajima, Yasushi Yatabe, Kengo Takeuchi, Toru Hamada, Hidenori Haruta, Yuichi Ishikawa, Hideki Kimura, Tetsuya Mitsudomi, Yoshiro Tanio, Hiroyuki Mano
Journal: New England Journal of Medicine (2010)

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.).
Bubble hair: a cosmetic abnormality caused by brief, focal heating of damp hair fibres
Authors: C.L. GUMMER
Journal: British Journal of Dermatology (1994)

Following investigation of two individuals with bubble hair abnormality, a reproducible cause has been established. Simple experiments showed that brief, focal heating of damp hair is sufficient to cause bubbles to form inside the hair fibres. This in turn results in weak, dry and brittle hair which breaks easily.