tbuckley/cabot-search huggingface dataset:
A Syndrome Resembling Addison's Disease
Authors: S. Locket
Journal: BMJ (1945)

A case resembling Addison's disease with a severe normocytic normochromic anaemia, which was at first treated as a macro- cytic anaemia of unknown aetiology, is here described.Addison (1855) in his original description of the disease mentioned anaemia, but it is not accepted nowadays as a common or characteristic feature of the syndrome (Goldzieher, 1939). Case RecordMiss A., aged 22, had a sudden attack of stomatitis in Feb., 1943.At times it was so severe that for several days she was unable to eat or drink.It continued until her admission to a military hospital on July 5, 1943.She had post-prandial upper abdominal pain and loose motions.Amenorrhoea had been present for three months.She was extremely ill, had a lemon-yellow tint, and was wasted Shallow ulcers were present inside the mouth.The spleen was not palpable and there were no changes in the nails.Blood picture on admission: haemoglobin, 36%; R.B.C., 1,600,000; colour index, 1.1; W.B.C., 2,000, with a normal differential white count; reticulocytes 0.1%; polychromasia; occasional Howell-Jolly bodies; marked anisocytosis; one primitive megaloblast, and one normoblast.Red-cell fragility was normal.She was treated with liver extract intramuscularly, iron, marmite, vitamin C, vitamins A and D, nicotinic acid, and a high-calorie diet.The stomatitis recurred several times.She apparently improved, and on discharge the blood picture was: haemoglobin, 92%; R.B.C., 41 millions; W.B.C., 9,000.A test meal showed that free acid was present.She was still feeling subnormal, however, and the amenor- rhoea persisted.She was discharged from the Forces in 1943, all treatment being discontinued.Two weeks before admission to the County Hospital, Pembury, on March 8, 1944, she had an attack of "influenza."A blood count showed R.B.C. 2,000,000.Liver injections were given without response.The temperature persisted.On admission she complained of lack of energy, dizziness, especially on standing, cold hands and feet, and sore mouth.There were no previous illnesses.Her mother, two stepbrothers, and two stepsisters were alive and well.Her father died from an unknown cause.
Hemoglobin loss from erythrocytes in vivo results from spleen-facilitated vesiculation
Authors: Frans L. A. Willekens, Bregt Roerdinkholder-Stoelwinder, Yvonne A. M. Groenen-Döpp, Harry J. Bos, Giel J. C. G. M. Bosman, Annegeet G. van den Bos, Arie J. Verkleij, Jan M. Werre
Journal: Blood (2002)
Measles in Adults
Authors: Kenneth H. Rand
Journal: JAMA (1976)

An outbreak of measles occurred in California in the first half of 1975, especially in the San Francisco Bay area. Of four adult patients with complicated cases, two were receiving immunosuppressive chemotherapy, and both died from a giant-cell pneumonia. The clinical presentation in such cases may be atypical, and special viral isolation and immunofluorescent techniques may be diagnostically helpful. A significant (P less than .0005) trend toward the occurrence of measles in adolescents was observed in this epidemic, which may also occur in future epidemics elsewhere. With wide spread but incomplete immunization, it is possible for the nonimmunized to reach adulthood without acquiring natural infection. As a result, internists as well as pediatricians will have to consider the possibility of measles and be aware of its serious potential in the immunosuppressed patient.
More varieties of Bayesian theories, but no enlightenment
Authors: Jeffrey S. Bowers, Colin J. Davis
Journal: Behavioral and Brain Sciences (2011)

Abstract We argue that Bayesian models are best categorized as methodological or theoretical . That is, models are used as tools to constrain theories, with no commitment to the processes that mediate cognition, or models are intended to approximate the underlying algorithmic solutions. We argue that both approaches are flawed, and that the Enlightened Bayesian approach is unlikely to help.
Dietary advice both significantly reduces colitis disease activity, steroid requirement and increases quality of life in patients with ulcerative colitis
Authors: M. Kyaw, T. Moshkovska, A. Bagewadi, J. Mayberry
Journal: Gut (2011)

Introduction The impact of food on the relapse of Ulcerative Colitis (UC) has not been clearly defined. Given the mixture of results from previous studies, patients with UC are confused about the role dietary factors may play in their disease. The purpose of this study is to investigate the effect dietary advice on Quality of Life in patients with UC and their disease activity. Methods 66 patients were randomly allocated to a treatment group and a control group. Patients in the treatment group were given dietary advice via booklet (‘Diet and Ulcerative Colitis’). Patient in the control group were given a general dietary booklet, which is normally used to give dietary advice to general public (‘Healthy Eating for a Healthy Leicestershire’). Patients were asked to complete IBDQ (Inflammatory Bowel Disease Questionnaire) and SCCAI (Simple Clinical Colitis Activity Index) together with the food frequency questionnaire at 0 week, 6 weeks and 32 weeks. IBDQ, SCCAI, food frequency questionnaires were used to compare patients perceived quality of life, colitis activity scores and eating habits, prior to and following dietary advice given. Results In the treatment group there were a smaller number of patients that required steroids compared to control group (5.5% vs 20.9%). There was a mean reduction in SCCAI score in the treatment group compared to an increase in the score in the control group (mean differences of −1.30 (p= 0.0108) vs 0.88 (p = 0.0249)). There was a mean increase in IBDQ score in the treatment group compared to a reduction in the score in the control group (mean differences of 7.1 (p=0.12) verses –3.4 (p=0.20)). 69 % of patients in the treatment group found the dietary advice significantly or moderately helpful. Conclusion Dietary advice reduces the number of patients requiring steroids compared to controls. There is improvement in SCCAI score and Quality of Life in those offered dietary advice. These findings require validation with further larger cohort of patients.
Interferon gamma plays a critical role in induced cell death of effector T cell: a possible third mechanism of self-tolerance.
Authors: Y Liu, C A Janeway
Journal: The Journal of Experimental Medicine (1990)

We have used anti-T cell monoclonal antibodies (mAbs) as mimic ligands to study the effects of T cell receptor (TCR) ligation of cloned T helper type 1 cells in the presence or absence of accessory cells. Our results demonstrate that ligation of the TCR in the absence of accessory cells rapidly induces cell death. Cell death can be prevented by addition of spleen adherent cells, leading to strong clonal expansion. Induced cell death is inhibited by cyclosporin A and by anti-interferon gamma (IFN-gamma), and is restored by adding exogenous recombinant IFN-gamma to cyclosporin A-treated cells. These results demonstrate that IFN-gamma plays a critical role in cell death induced by anti-TCR mAbs in the absence of costimulatory cells. We propose that induced cell death of active effector T cells provides a third mechanism of tolerance in addition to intrathymic deletion of developing autoreactive T cells and peripheral inactivation of mature, naive T cells.
Methotrexate dosage in patients aged over 50 with psoriasis.
Authors: G. M. Fairris, A. G. Dewhurst, J. E. White, M. J. Campbell
Journal: BMJ (1989)

In low-incidence countries of the European Union (EU), vulnerable populations are largely responsible for the lack of a faster decline of the tuberculosis (TB) incidence rate [1]. Above all, poor and marginalised people living in metropolitan areas [2, 3] have a greater risk of developing TB. In the last few years a large proportion of TB cases in EU occurred among the foreign-born [4] at a younger median age compared to native populations with TB [1, 5].
Erythropoietin and Neonatal Anemia
Authors: Ronald G. Strauss
Journal: New England Journal of Medicine (1994)

Premature infants weighing less than 1300 g receive multiple red-cell transfusions, primarily because of blood loss from repeated blood sampling to monitor respiratory disease and because of the anemia of prematurity -- a condition associated with low plasma erythropoietin levels. Premaure infants with anemia do produce erythropoietin, but have lower levels than older persons with this condition. Inadequate erythropoietin production, and not unresponsive red-cell progenitors, appears to be a major cause of neonatal anemia. It is unclear why plasma erythropoietin levels are low in newborn infants, but one reason is that during the first weeks of life the liver is . . .
Will you present the prizes?
Authors: A. Craft
Journal: BMJ (1998)

While taking my early Sunday morning exercise I had time to reflect on one of the most stressful episodes of my life. The story started six weeks before, when on the eve of my departure for Australia on a lecture tour the telephone rang and the headmaster of one of our local private schools invited me to present the prizes and say a few words at the school speech day. Seven to 10 minutes was all that was needed.

Being a relatively seasoned lecturer I could not immediately think of a good reason to say no. Four weeks, 25 000 miles, and 11 lectures later I was back in England looking at the next week's commitments. The entry “Speech Day” on Friday suddenly made me realise that I had better give it a bit of thought. Panic began to set in when I realised that I had no concept of what to say at a speech day. Almost 40 years ago I went to the local grammar school, which had nothing so grand …
Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8+cells in patients with hepatocellular carcinoma
Authors: Alessandro Zerbini, Massimo Pilli, Paolo Soliani, Stefanie Ziegler, Guido Pelosi, Alessandra Orlandini, Cristina Cavallo, Jacopo Uggeri, Renato Scandroglio, Pellegrino Crafa, Giulio C Spagnoli, Carlo Ferrari, Gabriele Missale
Journal: Journal of Hepatology (2003)
Smoking and psoriasis
Authors: E M Higgins, A W P Duvivier, T J Peters
Journal: BMJ (1994)

EDITOR, - Hywel C Williams reviews some of the published work on the link between smoking and psoriasis,1but without adequate controls it is not possible to say that smoking could be responsible for up to a quarter of cases of the disease. Most studies have examined smoking in isolation and have failed to …
Phase II, Randomized Study of Concomitant Chemoradiotherapy Followed by Surgery and Adjuvant Capecitabine Plus Oxaliplatin (CAPOX) Compared With Induction CAPOX Followed by Concomitant Chemoradiotherapy and Surgery in Magnetic Resonance Imaging–Defined, Locally Advanced Rectal Cancer: Grupo Cáncer de Recto 3 Study
Authors: Carlos Fernández-Martos, Carles Pericay, Jorge Aparicio, Antonieta Salud, MariaJose Safont, Bertomeu Massuti, Ruth Vera, Pilar Escudero, Joan Maurel, Eugenio Marcuello, Jose Luis Mengual, Eugenio Saigi, Rafael Estevan, Moises Mira, Sonia Polo, Ana Hernandez, Manuel Gallen, Fernando Arias, Javier Serra, Vicente Alonso
Journal: Journal of Clinical Oncology (2010)

PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.
Morphometry of arterioles and capillaries in hearts of senescent mice
Authors: K. Rakusan, J. Nagai
Journal: Cardiovascular Research (1994)

Objective: The aim was to characterise quantitative changes in the coronary arterioles and capillaries with aging in mice. Methods: Morphometric analysis of the coronary resistance vessels was carried out in 12 "young" mice (63 days) and 11 "old" mice (650 days). Results: Compared to hearts from young mice, those from senescent mice were heavier, contained less water, and differed in several variables characterising terminal vessels. The main changes were a decreased capillary and arteriolar density, increased heterogeneity of capillary spacing, and larger arterioles with thicker walls. Conclusions: Aging of the murine myocardium is characterised by important changes at the level of the terminal vascular bed, the most prominent being a decrease in capillary and arteriolar density. The decrease in arteriolar density is most prominent in the classes of smallest vessels. All these changes represent an impairment of geometrical conditions for the oxygen supply to the myocardial tissue. Cardiovascular Research 1994;28:969-972
The Diagnosis of Major Depression in End-Stage Renal Disease
Authors: Kathleen O’Donnell, Joyce Y. Chung
Journal: Psychotherapy and Psychosomatics (1997)

Although major depression commonly occurs in medically ill patients, it can be difficult to diagnose since depression and many medical illnesses share common physical symptoms.This study was designed to evaluate patients with end-stage renal disease (ESRD) for major depressive disorder using three diagnostic approaches, to assess the Beck Depression Inventory as a screening instrument for major depression, and to examine the association of anhedonia with a diagnosis of major depression in ESRD patients who deny depressed mood.Rates of major depression varied from 6 to 34% according to the criteria that were used. The sensitivity of the Beck Depression Inventory was found to be modest. Anhedonia was a helpful clue for diagnosing depression in patients who denied depressed mood.The findings illustrate the current difficulties in applying DSM criteria for major depression to medical patients and underscore the need for more specific guidelines.
An Operation for the Correction of Truncus Arteriosus
Authors: Dwight C. McGoon
Journal: JAMA (1968)

An operation achieved success in correcting the truncus arteriosus anomaly. The pulmonary arteries were disconnected from the truncus, and, by the manner in which the ventricular septal defect was closed, it became the true aorta. A new outflow from the right ventricle to the pulmonary arteries was established by the use of a homograft of ascending aorta including the aortic valve. This use of a homograft may be the factor that allowed success in the operation as opposed to previous attempts at similar operations with synthetic materials. The corrective operation will probably prove to be the method of choice for the treatment of patients with truncus arteriosus.
Neutrophil oxygen radical generation. Synergistic responses to tumor necrosis factor and mono/polyunsaturated fatty acids.
Authors: Y Li, A Ferrante, A Poulos, D P Harvey
Journal: Journal of Clinical Investigation (1996)

In inflammatory reactions there are complex interactions of protein mediators (cytokines) and mediators derived from lipids. An important event in inflammation is superoxide production, in relation to microbicidal activity as well as tissue damage. We have studied interactions of lipid mediators with a cytokine mediator tumor necrosis factor alpha (TNF) in stimulating superoxide production by human neutrophils for this reason and because it throws light on intracellular signals activating this response. Pretreatment of neutrophils with TNF markedly augmented the amount of superoxide produced in response to AA but not to either a 20 carbon saturated fatty acid, or the hydroxy- or hydroperoxy-derivatives of AA. Not only were other polyunsaturated fatty acids (eicosapentanoic, docosahexaenoic, linolenic, linoleic acid) as effective as AA but so was the monounsaturated fatty acid, oleic acid. Indeed TNF primed the neutrophils for an increased response to a major mediator of inflammation, leukotriene B4, which is a product of AA metabolism via the lipoxygenase pathway. The data demonstrate that two major types of mediators generated during an inflammatory response have synergistic action on neutrophils in the generation of reactive oxygen species. In contrast, neutrophils primed with TNF and challenged with PGE2, a product of AA metabolism via the cyclooxygenase pathway, showed a reduced chemiluminescence response. This identifies an important interaction between unsaturated lipids and cytokines which is likely to play a critical role in disease processes and nutrient modulation of the immune responses.
Role of Histamine Produced by Bone Marrow–Derived Vascular Cells in Pathogenesis of Atherosclerosis
Authors: Yasuyuki Sasaguri, Ke-Yong Wang, Akihide Tanimoto, Masato Tsutsui, Hikaru Ueno, Yoshitaka Murata, Yukari Kohno, Sohsuke Yamada, Hiroshi Ohtsu
Journal: Circulation Research (2005)

To clarify the role of histamine-producing cells and its origin in atherosclerosis, we investigated histidine decarboxylase (HDC; histamine-producing enzyme) expression in murine arteries with vascular injuries after the animal had received transplanted bone marrow (BM) from green fluorescent protein (GFP)–transgenic mice. The neointima in the ligated carotid arteries contained BM-derived HDC + cells that expressed macrophage (Mac-3) or smooth muscle cell antigen (α-SMA). In contrast, the HDC + BM-derived cells, which were positive for Mac-3, were mainly located in the adventitia in the cuff replacement model. In apolipoprotein E-knockout mice on a high cholesterol diet, BM-derived cells expressing Mac-3 in the atheromatous plaques were also positive for HDC. In comparison with wild-type mice, HDC −/− mice showed reduced neointimal thickening and a decreased intima-to-media ratio after ligation and cuff replacement. These results indicate that histamine produced from BM-derived progenitor cells, which could transdifferentiate into SMC- or macrophage-like cells, are important for the formation of neointima and atheromatous plaques.
GE-21 * DRASTIC GENOMIC DIVERGENCE OF RECURRENT MEDULLOBLASTOMA INVALIDATES TARGETED THERAPIES DISCOVERED AT DIAGNOSIS
Authors: S. Morrissy, L. Garzia, M. Remke, V. Ramaswamy, F. Jorgensen, X. Wu, S. Shah, Y. Ma, K. Mungall, T. Van Meter, Y.-J. Cho, P. Collins, T. MacDonald, X.-N. Li, R. Moore, P. Northcott, S. Pfister, D. Malkin, M. Marra, M. Taylor
Journal: Neuro-Oncology (2014)

Recurrence of the childhood brain cancer medulloblastoma is almost universally fatal. The current strategy for clinical trials is to test novel therapies at the time of recurrence, using targets discovered at diagnosis. To define the relationship between naïve and post-treatment medulloblastoma, we developed a functional genomic transposon-driven mouse-model. Deep sequencing of the commonly inserted genes in diagnostic and recurrent tumors revealed dramatic divergence post-therapy, with recurrences demonstrating a convergence on the TP53 pathway. Loss of function insertions in Tp53 are clonal in the recurrence, result in loss of expression of the Tp53 target gene P21, and arise through selection of minor subclones present before therapy. The majority of insertions identified at diagnosis are no longer present at recurrence, and therefore represent futile targets for therapy. To validate these findings, we studied 36 pairs of human primary/recurrent tumors by whole genome sequencing. When comparing SNVs, indels or structural aberrations, we found minimal genetic overlap between the dominant clones at diagnosis versus recurrence. Recurrent tumors have more genomic aberrations than their paired diagnostic sample, and commonly display alterations in the TP53 (SHH), or the TP53 and TGF-β pathways (Group 3/4 tumors). Clonal dynamics between primary and recurrent tumors was measured using ultra-deep sequencing (1,500X). Overall, recurrent tumors share little genetic identity with their diagnostic tumor, arise through clonal selection, target specific signaling pathways to avoid cell death, and assume clinical dominance after therapy. Our findings undermine the key assumption that diagnostic medulloblastoma samples provide rational targets for therapy in recurrent disease, and provide a simple reason for the failure of prior trials of targeted therapy. Repeated genetic convergence on specific signaling pathways at the time of recurrence suggests that it may be possible to develop ‘anticipatory therapy’ delivered up front to prevent the later emergence of minor resistant clones driving recurrence.
Taking the long view: an emerging framework for translational psychiatric science
Authors: Kenneth W.M. Fulford, Lisa Bortolotti, Matthew Broome
Journal: World Psychiatry (2014)

Understood in their historical context, current debates about psychiatric classification, prompted by the publication of the DSM-5, open up new opportunities for improved translational research in psychiatry. In this paper, we draw lessons for translational research from three time slices of 20th century psychiatry. From the first time slice, 1913 and the publication of Jaspers' General Psychopathology, the lesson is that translational research in psychiatry requires a pluralistic approach encompassing equally the sciences of mind (including the social sciences) and of brain. From the second time slice, 1959 and a conference in New York from which our present symptom-based classifications are derived, the lesson is that, while reliability remains the basis of psychiatry as an observational science, validity too is essential to effective translation. From the third time slice, 1997 and a conference on psychiatric classification in Dallas that brought together patients and carers with researchers and clinicians, the lesson is that we need to build further on collaborative models of research combining expertise-by-training with expertise-by-experience. This is important if we are to meet the specific challenges to translation presented by the complexity of the concept of mental disorder, particularly as reflected in the diversity of desired treatment outcomes. Taken together, these three lessons – a pluralistic approach, reliability and validity, and closer collaboration among relevant stakeholders – provide an emerging framework for more effective translation of research into practice in 21st century psychiatry.
Selective estrogen receptor modulator raloxifene inhibits the cardiac hypertrophy and dysfunction due to aortic banding in mice
Authors: Hisakazu Ogita, Koichi Node, Hiroshi Asanuma, Shoji Sanada, Seiji Takashima, Tetsuo Minamino, Masanori Asakura, Jiyoong Kim, Yulin Liao, Yoshihiro Asano, Yasunori Shintani, Ken-ichiro Okada, Masashi Fujita, Akio Hirata, Osamu Tsukamoto, Masatsugu Hori, Masafumi Kitakaze
Journal: Journal of the American College of Cardiology (2003)