tbuckley/cabot-search huggingface dataset:
Studies on the Origin of Testosterone in the Urine of Normal Adult Subjects and Patients with Various Endocrine Disorders*
Authors: Alvro M. Camacho, Claude J. Migeon
Journal: Journal of Clinical Investigation (1964)

We have recently described a procedure for the isolation of testosterone 1 from human urine after P-glucuronidase hydrolysis, indicating that it was conjugated with glucuronic acid (1).We also reported on the urinary excretion of testosterone in adult subjects and in patients with endocrine disorders.The concentration of 17-ketosteroids in bio- logical fluids is commonly used as an index of virilization.Frequently, however, there is no correlation between the degree of virilism observed in patients and levels of the 17-ketosteroids in blood or urine.Testosterone could be produced by such patients in amounts sufficient to cause virilization without appreciably increasing the levels of 17-ketosteroids in biological fluids.If a relatively constant quantity of testosterone produced in the body is converted to testosterone glucuronide and if other secreted steroids are not converted in significant amounts to testosterone glucuronide, then its urinary levels should reflect the production of testosterone and correlate better with the degree of virilism.The purpose of this study, therefore, was to determine the constancy of conversion of testos- terone to its glutcuronide conjugate and to what extent other closely related steroids are metabo-
Calcitonin for multiple fractures in Paget's disease.
Authors: G A Evans, G C Slee
Journal: BMJ (1977)

<h3>ABSTRACT</h3> Only a minority of the many genomic clusters of transcription factor binding motifs (TFBM) act as transcriptional enhancers. To identify determinants of enhancer activity, we randomized the spacer sequences separating the ETS and GATA sites of the early neural enhancer of the tunicate <i>Ciona intestinalis Otx</i> gene. We show that spacer sequence randomization affects the level of activity of the enhancer, in part through distal effects on the affinity of the transcription factors for their binding sites. A possible mechanism is suggested by the observation that the shape of the DNA helix within the TFBM can be affected by mutation of flanking bases that modulate transcription factor affinity. Strikingly, dormant genomic clusters of ETS and GATA sites are awakened by most instances of spacer randomization, suggesting that the sequence of naturally-occurring spacers ensures the dormancy of a majority of the large reservoir of TFBM clusters present in a metazoan genome.
Urinary xylose excretion in steatorrhoea
Authors: M. Shiner, B. J. Vakil, P. B. Wilcox
Journal: Gut (1962)

The urinary xylose excretion is low in patients with untreated idiopathic steatorrhoea but subsequent improvement in excretion was noted after treatment in six out of nine patients. This did not coincide with histological improvement. With Crohn9s disease low values were found when the jejunum but not the ileum was involved.
Assessment of Relationship between Subclinical Atherosclerosis and Benign Prostat Hyperplasia using Epicardial Fat Thickness and Carotid Intima-Media Thickness
Authors: Turhan Turan, Tayyar Gökdeniz, Hasan Rıza Aydın, Ali Rıza Akyüz, Hasan Turgut, Yılmaz Ofluoğlu, Ahmet Çağrı Aykan, İlker Gül, Selim Kul, Alimdar Şimşek, Ali Tüten, Ayça Ata Korkmaz
Journal: Journal of the American College of Cardiology (2013)
Late presentation of diaphragmatic hernia.
Authors: R. J. Aitken
Journal: BMJ (1988)

give no suggestion that opposed treatment is hazardous with respect to ischaemic heart disease, we agree with Professor Beaglehole's assertion that it is premature to recommend postmenopausal hormones to prevent cardiovascular disease.On the issue of selection bias we, like many of the studies, found a protective effect on all cause mortality.This was reflected across all mortality from specific causes with two exceptions: firstly, we found a slight (but non-significant) excess of cancer of the ovary, and, secondly, in contrast with the Walnut Creek study2 our data showed an excess ofdeaths attributed to suicide or suspected suicide.
Mechanical Circulatory Support for Advanced Heart Failure
Authors: Garrick C. Stewart, Michael M. Givertz
Journal: Circulation (2012)

A fter nearly 50 years of clinical development, durable mechanical circulatory support (MCS) devices are widely available for patients with advanced heart failure.The field of circulatory support has matured dramatically in recent years, thanks to the advent of smaller, rotary pumps.The resulting transition away from older pulsatile devices has been swift.Accelerated use of continuous-flow left ventricular assist devices (LVADs) for long-term support has changed the face of advanced heart failure care.MCS candidate selection, risk stratification, and management strategies are evolving in tandem with new pump technology, producing a shift in the profiles of patients being considered for MCS.Timely referral for MCS evaluation and appropriate implantation now depends on familiarity with recent advances in pump design and clinical outcomes.This review, the first in a series on Advances in Mechanical Circulatory Support, will focus on durable intracorporeal LVADs used in adults with advanced heart failure, and highlight the evolution in both patients and technology.
Gamma-globulin treatment of acute myocarditis in the pediatric population.
Authors: N A Drucker, S D Colan, A B Lewis, A S Beiser, D L Wessel, M Takahashi, A L Baker, A R Perez-Atayde, J W Newburger
Journal: Circulation (1994)

BACKGROUND Myocardial damage in myocarditis is mediated, in part, by immunological mechanisms. High-dose intravenous gamma-globulin (IVIG) is an immunomodulatory agent that is beneficial in myocarditis secondary to Kawasaki disease, as well as in murine myocarditis. Since 1990, the routine management of presumed acute myocarditis at Children's Hospital, Boston, and Children's Hospital, Los Angeles, has included administration of high-dose IVIG. METHODS AND RESULTS We treated 21 consecutive children presenting with presumed acute myocarditis with IVIG, 2 g/kg, over 24 hours, in addition to anticongestive therapies. A comparison group comprised 25 recent historical control patients meeting identical eligibility criteria but not receiving IVIG therapy. Left ventricular function was assessed during five time intervals: 0 to 7 days, 1 to 3 weeks, 3 weeks to 3 months, 3 to 6 months, and 6 to 12 months. At presentation, the IVIG and non-IVIG groups had comparable left ventricular enlargement and poor fractional shortening. Compared with the non-IVIG group, those treated with IVIG had a smaller mean adjusted left ventricular end-diastolic dimension and higher fractional shortening in the periods from 3 to 6 months (P = .008 and P = .033, respectively) and 6 to 12 months (P = .072 and P = .029, respectively). When adjusting for age, biopsy status, intravenous inotropic agents, and angiotensin-converting enzyme inhibitors, patients treated with IVIG were more likely to achieve normal left ventricular function during the first year after presentation (P = .03). By 1 year after presentation, the probability of survival tended to be higher among IVIG-treated patients (.84 versus .60, P = .069). We observed no adverse effects of IVIG administration. CONCLUSIONS These data suggest that use of high-dose IVIG for treatment of acute myocarditis is associated with improved recovery of left ventricular function and with a tendency to better survival during the first year after presentation.
Eyelid Swelling and Primary Sjögren's Syndrome
Authors: Jian-Wei Zhu, Jian-You Wang
Journal: New England Journal of Medicine (2013)

A 43-year-old woman with a 3-year history of sleep disturbances, dry mouth, and dry eyes presented with upper-eyelid swelling that had progressed during the past several months. Physical examination revealed nontender enlargement of the lacrimal and submandibular salivary glands.
Role of two‐dimensional electrophoretic analysis in the diagnosis and characterization of IgD monoclonal gammopathy
Authors: F. Spertini, J. D. Tissot, N. Dufour, C. Francillon, P. C. Frei
Journal: Allergy (1995)

Over a period of 5 years, an isolated light chain ‘K = 9, λ= 12) was detected in 21 sera by immunofixation electrophoresis. Further analysis with anti‐δ‐ and anti‐ɛ‐specific antisera identified four δ heavy chains, all associated with a λ light chain, and no ɛ heavy chains. For evaluation of the role of two‐dimensional polyacrylamide gel electrophoresis ‘2D‐PAGE) in the diagnosis of IgD paraproteins, as a possible alternative or complement to immunofixation, IgD paraproteins were retrospectively analyzed by 2D‐PAGE. δ Heavy chains migrated to gel areas clearly distinguishable from other heavy chains α, γ, or μ, and in a wide range of isoelectric points ‘pl: 5.4‐8). In one serum, the monoclonal δ chain had a pi range comparable to that of albumin and was undetectable. However, all four δ chains were easily identified when analyzed from affinity‐purified immunoglobulin fractions. These observations showed the following: 1) IgD paraproteins are not rare among apparently isolated monoclonal light chains detected by routine immunofixation, Ostrongly confirming the need for further analysis with anti‐δ antisera, before assumption of a light‐chain disease. 2) 2D‐PAGE analysis of affinity‐purified immunoglobulin fractions allowed correct identification of IgD monoclonal gammopathies in all cases. 3) However, although 2D‐PAGE analysis is now easy to perform, well standardized, and highly sensitive, this technique remains time‐consuming and expensive, and does not appear suitable for routine practice as a first‐line diagnostic procedure. 2D‐PAGE should find its place as a complement to immunofixation and in the definitive demonstration, in selected ambiguous cases, of the clonal pattern of a suspected gammopathy at immunofixation.
NHS is Commons combat zone
Authors: J. Warden
Journal: BMJ (1998)

The NHS acquired a higher political profile this week with the appointment of Ann Widdecombe as opposition health spokesperson in the Conservative shadow cabinet.

Acknowledged to be one of the most combative parliamentarians, Miss Widdecombe has been brought from the backbenches by opposition leader William Hague with the clear intention of targeting the stewardship of the NHS. The NHS has surprisingly become the Achilles heel of …
HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families
Authors: Henry A. Erlich, Adina Zeidler, Julie Chang, Sylvia Shaw, Leslie J. Raffel, William Klitz, Yolanda Beshkov, Gertrude Costin, Sheila Pressman, Teodorica Bugawan, Jerome I. Rotter
Journal: Nature Genetics (1993)
Abstract 2273: c-Rel is a critical mediator of NF-κB-dependent apoptosis resistance of pancreatic cancer cells against TRAIL
Authors: Claudia Geismann, Frauke Grohmann, Gabriele Wirths, Susanne Sebens, Anita Dreher, Robert Häsler, Sebastian Zeissig, Stefan Schreiber, Philip Rosenstiel, Heiner Schäfer, Alexander Arlt
Journal: Cancer Research (2014)

Abstract Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies with an overall life expectancy of six months despite palliative radio-chemotherapy. The transcription factor NF-κB has been shown to be a critical component of dysregulated transcription factor activity conferring this profound resistance against chemotherapeutic drugs and death receptor induced apoptosis. Despite extensive data on the role of the most abundant NF-κB subunit p65/RelA in PDAC apoptosis control, only little knowledge of the role of the subunit c-Rel in solid cancers exists. In the present study, three pancreatic carcinoma cell lines (Panc1, Patu8988t, MiaPaca2) were analysed for the role of c-Rel in resistance against TRAIL induced apoptosis. TRAIL resistant Panc1 and Patu8988 cells exhibit a strong TRAIL inducible NF-κB activity, whereas TRAIL sensitive MiaPaca2 cells displayed only a small increase in NF-κB binding activity. Transfection with siRNA against the c-Rel subunit of NF-κB sensitized the TRAIL resistant cells in a comparable fashion like siRNA targeting the p65/RelA subunit. Gel shift analysis revealed that together with the p65/RelA subunit, c-Rel is part of the TRAIL inducible NF-κB complex in PDAC. Array analysis results suggested NFATc2 as a c-Rel target gene that is one of the 15 strongest TRAIL inducible genes in apoptosis-resistant Panc1 cells. siRNA targeting c-Rel strongly reduced TRAIL induced NFATc2 activity in TRAIL resistant PDAC cells. Furthermore siRNA targeting NFATc2 sensitized these PDAC cells against TRAIL induced apoptosis. Finally, TRAIL induced expression of COX-2 was strongly reduced through siRNA targeting c-Rel or NFATc2 and pharmacological inhibition of COX-2 with celecoxib strongly increased TRAIL apoptosis. In conclusion, c-Rel is a critical mediator of NF-κB dependent anti-apoptotic signalling in PDAC through activation of NFATc2 and COX-2. Citation Format: Claudia Geismann, Frauke Grohmann, Gabriele Wirths, Susanne Sebens, Anita Dreher, Robert Häsler, Sebastian Zeissig, Stefan Schreiber, Philip Rosenstiel, Heiner Schäfer, Alexander Arlt. c-Rel is a critical mediator of NF-κB-dependent apoptosis resistance of pancreatic cancer cells against TRAIL. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2273. doi:10.1158/1538-7445.AM2014-2273
Leukemic challenge unmasks a requirement for PI3Kδ in NK cell–mediated tumor surveillance
Authors: Eva Zebedin, Olivia Simma, Christian Schuster, Eva Maria Putz, Sabine Fajmann, Wolfgang Warsch, Eva Eckelhart, Dagmar Stoiber, Eva Weisz, Johannes A. Schmid, Winfried F. Pickl, Christian Baumgartner, Peter Valent, Roland P. Piekorz, Michael Freissmuth, Veronika Sexl
Journal: Blood (2008)
p53 mutational status, but not immunohistochemical staining (IHC), is associated with a clinical response of the primary tumor in women receiving neoadjuvant docetaxel-capecitabine chemotherapy for locally advanced breast cancer.
Authors: JS Ross, CM Perou, N Aki, N Patten, L Wu, EF McKenna, H Lawrence, M Royce, E Avisar, S Gluck
Journal: Cancer Research (2009)

Abstract Abstract #6047 Background: The XeNa trial enrolled 157 patients in a multicenter Phase II study of neoadjuvant capecitabine and docetaxel in women with operable early stage breast cancer (T2-T3, N0-N1). HER2-positive patients also received trastuzumab. The primary endpoint was the rate of pathological complete response (pCR; residual cancer burden [RCB] = 0) and near-complete response (npCR; RCB = 1). A secondary endpoint of the study was to evaluate the association between p53 alterations and response to chemotherapy.&amp;#x2028; Methods: p53 status was assessed in by mutational analysis on all cases using a microarray-based resequencing assay (AmpliChip p53 – Roche Molecular Systems, Pleasanton, CA); and also by IHC (using the Bp-53-11 antibody (CONFIRM™, Ventana, Tucson, AZ) in 120/157 (76%) of the cases. Gene expression profiling for breast cancer subtypes was also performed using a new 50-gene centroid-based method.&amp;#x2028; Results: p53 mutations were detected in 78/157 (50%) of cases with 70% missense, 17% nonsense, 11% frame shift and 1% splice site. Silent mutations were rare (1%). Concordance of AmpliChip mutation status with IHC + staining was 65% (78/120 samples). Of the 16/60 (27%) cases which were IHC - and AmpliChip p53 mutation +, 10 (63%) had non-missense mutations which are typically IHC -. In the 60 mutation negative cases with IHC data, there were 26/60 (46%) IHC + cases. p53 mutation + status by AmpliChip was highest in Basal-like (75%) and HER2-enriched (57%) subtypes and lower in Luminal A (29%), Luminal B (12%) and Normal-like (39%). p53 IHC + staining varied little among the subtypes (35 to 50%) and did not correlate with p53 mutational status. The frequency of pCR and npCR was significantly higher in cases with p53 sequence mutations (20/58 - 35%) than in patients without mutations (7/52 - 13%; p = 0.014; 2-tailed Fisher's Exact Test), and this trend was apparent in both HER2+ and HER2- cases. IHC status did not correlate with treatment response (18% pCR and npCR in IHC- cases vs. 27% in IHC + cases; p = 0.35). Notably 3 cases achieving pCR had non-missense p53 mutations and were IHC -.&amp;#x2028; Conclusion: P53 mutations were found in 50% of locally advanced breast cancers and were more frequent in Basal-like and HER2-enriched subtypes and less common in other subtypes. IHC staining lacks sensitivity and specificity for the presence of p53 mutations. In contrast to studies of anthracycline-based therapy, tumors harboring p53 mutations, especially missense mutations, respond better to this taxane-based regimen than wild-type tumors. P53 mutational analysis is a more accurate predictor of treatment response than IHC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6047.
TCT-747 Transcatheter Aortic Valve Replacement: Assessment of the Learning Curve Based on the PARTNER Trial
Authors: Oluseun Alli, Charanjit Rihal, Rakesh Suri, Kevin Greason, Ron Waksman, Sa'ar Minha, Rebecca Torguson, Augusto Pichard, Michael Mack, Lars Svensson, Jeevanantham Rajeswaran, Ashley M. Lowry, Eugene Blackstone, E. Murat Tuzcu, Vinod Thourani, Raj Makkar, Martin Leon, David Holmes
Journal: Journal of the American College of Cardiology (2013)
Human Louse in Transmission of T. Duttoni
Authors: R. B. Heisch
Journal: BMJ (1949)

Hitherto there has been no evidence that the human louse can act as a vector of Treponema duttoni in nature.Even in the laboratory Nicolle and Anderson (1927) were unable to infect lice with a Congo strain of the parasite.Recently, however, Heisch and Garnham (1948) have shown that under laboratory conditions several strains of East African T. duttoni can infect and undergo metacyclic development in lice, and that the infection can be transmitted by inoculation.The present paper reports the discovery of natural infections in lice of spirochaetes indistinguishable from T. duttoni.rhe only other worker to have experimented along these lines is Blanchard (1914), who in the Congo inoculated mice with lice collected from patients infected by T. duttoni, but with negative results.Lice were collected from the clothes of patients infected with T. duttoni at Kisumu and other places in Kenya Colony where the disease is endemic; after being kept for varying periods they were emulsified with saline and inoculated into rats and mice.Lice were collected from seven patients, and four of the batches proved infective.Case 1.-Ten lice (L19) were collected on Aug. 26, 1946.
The proteome of Toll-like receptor 3–stimulated human immortalized fibroblasts: Implications for susceptibility to herpes simplex virus encephalitis
Authors: Rebeca Pérez de Diego, Claire Mulvey, Mark Crawford, Matthew W.B. Trotter, Lazaro Lorenzo, Vanessa Sancho-Shimizu, Laurent Abel, Shen-Ying Zhang, Jean-Laurent Casanova, Jasminka Godovac-Zimmermann
Journal: Journal of Allergy and Clinical Immunology (2013)
CD4 T cells transduced with CD80 and 4-1BBL mRNA induce long-term CD8 T cell responses resulting in potent antitumor effects
Authors: Hyun-Il Cho, Hye-Mi Park, Hyun-Jung Shon, Tai-Gyu Kim
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Therapeutic cancer vaccines are an attractive alternative to conventional therapies to treat malignant tumors, and more importantly, to prevent recurrence after primary therapy. However, the availability of professional antigen-presenting cells (APCs) has been restricted by
Prolonged Glucagon Infusion in Cardiac Failure
Authors: Gerald C. Timmis
Journal: JAMA (1973)

Twelve courses of continuous glucagon infusion were administered to ten patients at rates of 0.5 to 16 mg/hr for periods of 5 to 166 hours. Six infusions were given for chronic refractory congestive failure, three for postperfusion low flow, and three for cardiogenic shock. Improvement was noted in nine of ten patients including all with chronic congestive failure. Half of the latter group were discharged whereas only one of four patients with acute myocardial impairment survived. Side effects were frequent but mild. One patient, however, had three episodes of ventricular fibrillation associated with hypokalemia. Most patients developed an as yet unexplained increase in blood urea nitrogen.  This is the third favorable report of seven such studies involving chronic congestive failure and indicates the necessity for further observations in such patients and in those with chronic obstructive lung disease with cor pulmonale.
Neonate With Abdominal Calcifications
Authors: Claire Beetlestone
Journal: JAMA (1978)

<h3>History</h3> Progressive tympanic abdominal distension with markedly reduced chest excursions and concomitant respiratory distress developed in a neonate who was delivered by cesarean section after a prolonged labor. He became increasingly pale and shocked. He died within hours of birth. Figures 1 and 2 are flat and upright views of the abdomen without contrast medium. <h3>Diagnosis</h3> Spontaneous rupture of the gut with tension pyopneumoperitoneum in a neonate. <h3>Comment</h3> The erect film of the chest and abdomen (Fig 1) shows bilateral collapsed lungs. A long air-fluid level bisects the horizontal midplane of the distended abdomen. Air-filled bowel loops float in the midline near the top and above the fluid level. The intraperitoneal air seems to be draped over the liver and spleen, which are displaced downward and medially, leaving bilateral radiolucencies in a saddlebag configuration. The falciform ligament is outlined by air. The supine film (Fig 2) shows a large, centrally
Discovery of a Renal Medullary Carcinoma in an Adolescent Male With Sickle Cell Trait by Tc-99m Methylene Disphosponate Bone Scintigraphy
Authors: Jerry M. Brown, Bryan D. Berkey, John A. Brooks
Journal: Clinical Nuclear Medicine (2008)

The renal excretion of Tc-99m bone imaging agents often permits the identification of urinary tract abnormalities on bone scans. In this case report, identification of focal intrarenal stasis of the excreted bone imaging agent led to additional anatomic imaging and the identification of a renal medullary carcinoma (RMC) in an adolescent black male undergoing evaluation for back pain. RMC is a rare, highly aggressive renal neoplasm found almost exclusively in young individuals with sickle cell trait (SCT) or hemoglobin SC disease. The prognosis of RMC is poor because the malignancy is usually refractory to chemotherapy and radiotherapy, with metastatic disease commonly present at the time of diagnosis.
John Godfrey Ball
Authors: D. Brownridge, M. Wilson
Journal: BMJ (2012)

After service in the Royal Army Medical Corps (RAMC), hospital posts in the Birmingham area and a traineeship in Stourport, John Godfrey Ball succeeded to a single handed practice in Foley Park, Kidderminster, in 1957, where he developed a forward looking group practice. Throughout his career John always generated warmth and humour, which is still remembered by his patients, long after he retired in 1995.

Even in his early days in general practice John was active in medical politics, forming the Kidderminster General Practitioners Association in 1963 to fight the closure of the local maternity unit, a consequence of Enoch Powell’s hospital plan. He also served on the Worcestershire Local Medical Committee and in 1968 was elected as the regional representative on the General Medical Services Committee (GMSC, now the GPC), the national body representing all general practitioners. Although he went on to achieve eminence in medical politics, he never lost touch with his practice and his local colleagues. An active BMA member, he was chairman of the local BMA division in …