tbuckley/cabot-search huggingface dataset:
Triplet Repeat Expansion Mutations: The Example of Fragile X Syndrome
Authors: S T Warren, C T Ashley
Journal: Annual Review of Neuroscience (1995)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Histopathological Support of Antagonism of Allergen‐Induced Mast Cell Mediator Release in Human Skin by a Beta<sub>2</sub>‐Agonist
Authors: R. Gronnkberg, B. Lagerholm
Journal: Allergy (1986)

The site of antagonistic action on allergen‐induced early skin reactions by the beta 2 ‐agonist terbutaline was studied by light microscopy in 10 atopic subjects. Pretreatment with 1 μg terbutaline intradermally 5 min prior to challenge with horse dander allergen produced an approximate inhibition of 85 and 55% of flare and wheal responses respectively ( P &lt; 0.001) Biopsy specimens obtained from skin sites injected with allergen alone showed a reduced number of remaining stainable mast cells as compared to sites injected with terbutaline prior to allergen ( P &lt; 0.05, Sign test). The data support the concept of in viva inhibition of the mast cell mediator release reaction in atopic skin by terbutaline.
Platelet glycoproteins Ia, Ic, and IIa are physicochemically indistinguishable from the very late activation antigens adhesion-related proteins of lymphocytes and other cell types.
Authors: K D Pischel, H G Bluestein, V L Woods
Journal: Journal of Clinical Investigation (1988)

The very late activation antigens (VLA) are a subset of the superfamily of cell surface glycoproteins that serve as receptors from extracellular matrix proteins. One or more of the VLA heterodimers are present on T lymphocytes and most other cell types, including platelets. We have used VLA-specific monoclonal antibodies to isolate the reactive platelet membrane molecules. We have identified them as previously characterized platelet surface glycoproteins and have compared them with VLA molecules isolated from lymphocytes and other cells. Utilizing one-dimensional SDS-PAGE, two-dimensional O'Farrell gel electrophoresis, and nonreduced-reduced two-dimensional gel electrophoresis, we show that reduced VLA molecules of platelets are composed of three chains of molecular weights 165,000, 145,000, and 140,000 that possess the physicochemical properties of platelet glycoproteins GPIa, GPIc alpha, and GPIIa. GPIa corresponds to the VLA 165,000 alpha 2-chain, GPIIa corresponds to a 145,000 Mr VLA beta-chain, and GPIc alpha corresponds to a 140,000 Mr VLA alpha-chain. The polypeptide structure of VLA molecules on platelets and lymphocytes are very similar or identical. Platelet proteins GPIa and GPIIa exist as a mixed heterodimer in detergent lysates and correspond with the VLA-2 heterodimer found on activated T lymphocytes and other cell types. The platelet glycoproteins GPIIa and GPIc form a second mixed heterodimer. The mAb A-1A5, which binds to the VLA beta chain, binds to platelet GPIIa and precipitates both the GPIIa-GPIa and GPIIa-GPIc heterodimers, and binds to 4,926 +/- 740 sites per platelet. A VLA-2-specific mAb, 12F1, which binds to the VLA alpha 2-chain reacts with GPIa and immunoprecipitates only the GPIIa-GPIa heterodimer, and binds to 1,842 +/- 449 sites per platelet. The similarity of VLA chains and platelet GPIIa, GPIa, and GPIc molecules suggests that these molecules may have similar functions on various cell types.
Phase II Study of Pemetrexed for Second-Line Treatment of Transitional Cell Cancer of the Urothelium
Authors: Christopher J. Sweeney, Bruce J. Roth, Fairooz F. Kabbinavar, David J. Vaughn, Michael Arning, Rafael E. Curiel, Coleman K. Obasaju, Yanping Wang, Steven J. Nicol, Donald S. Kaufman
Journal: Journal of Clinical Oncology (2006)

Purpose To assess the antitumor activity and toxicity of pemetrexed as second-line chemotherapy in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium. Patients and Methods Eligible patients had a performance status of 0 or 1, adequate organ function, previous treatment with one prior chemotherapy regimen for locally advanced or metastatic TCC of the urothelium or relapsed within 1 year of adjuvant or neoadjuvant treatment. Patients received pemetrexed 500 mg/m 2 intravenously on day 1 every 21 days, with vitamin B 12 , folic acid, and dexamethasone prophylaxis. Results Forty-seven patients were enrolled and included in the intent-to-treat efficacy analysis. Responses: 3 (6.4%) complete responses and 10 (21.3%) partial responses produced an overall response rate of 27.7%. Ten patients (21.3%) had stable disease and 22 patients (46.8%) progressed. The median time to progressive disease was 2.9 months (95% CI, 1.7 months to 4.6 months) and median overall survival was 9.6 months (95% CI, 5.1 months to 14.6 months). Median duration of response was 5.0 months (95% CI, 3.9 months to 13.8 months). Of the 47 patients assessable for safety, grade 3 or 4 hematologic events were thrombocytopenia (8.5%; 0.0%), neutropenia (4.3%; 4.3%) and anemia (2.1%; 2.1%), respectively. Nonlaboratory toxicities included grade 4 stomatitis/pharyngitis, sepsis syndrome (one patient each), and grade 3 fatigue (three patients) and diarrhea (two patients). Conclusion Single-agent pemetrexed is safe and active as second-line treatment of patients with advanced TCC of the urothelium. Additional evaluation in the first- or second-line setting in TCC of the urothelium is warranted.
Cirrhosis: new research provides a basis for rational and targeted treatments
Authors: J. P Iredale
Journal: BMJ (2003)

Science, medicine, and the future Cirrhosis: new research provides a basis for rational and targeted treatments John P Iredale Liver transplantation and antiviral treatments for hepatitis have improved the outlook for many patients with liver disease.For patients with cirrhosis, new developments herald targeted treatmentsIt is an exciting time to be working in hepatology.The success of liver transplantation and the advances in the radiological and endoscopic management of portal hypertension have improved the longevity and quality of life of patients with liver cirrhosis.Additionally, the development of effective antiviral treatments means that disease can be cured in many patients infected with hepatitis B and hepatitis C.However, these interventions also serve to highlight our current impotence in altering the underlying fibrotic process in many patients with liver disease.This rather depressing perspective may soon change: data from clinical and laboratory based research are showing that cirrhosis may be reversible.By highlighting the attributes required of an effective antifibrotic, a new dynamic model is likely to lead to the development of targeted treatment for liver cirrhosis.
Addition of Lomustine to Idarubicin and Cytarabine Improves the Outcome of Elderly Patients With De Novo Acute Myeloid Leukemia: A Report From the GOELAMS
Authors: Arnaud Pigneux, Jean-Luc Harousseau, Francis Witz, Mathieu Sauvezie, Marie-Christine Bene, Isabelle Luquet, Mathilde Hunault-Berger, Christian Recher, Bruno Lioure, Chantal Himberlin, Martine Escoffre-Barbe, Christian Berthou, Severine Lissandre, Nathalie Fegueux, Jean-Yves Cahn, Eric Jourdan, François Dreyfus, Josy Reiffers, Noël Milpied, Norbert Ifrah
Journal: Journal of Clinical Oncology (2010)

No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML.The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m(2), days 1 through 5) and cytarabine (100 mg/m(2), days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m(2) orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine.The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P < .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 +/- 2.2 months v 8.7 +/- 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age < or = 69 years (P < .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P < .001).Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.
Falling in and out of consciousness: catatonia in a postoperative patient
Authors: David O'Regan, Kathie Wong, Irene Bouras, Carole Foot, Timothy Wigmore
Journal: Journal of the Royal Society of Medicine (2010)

A 51-year-old Burmese woman with no family orpersonal history of psychiatric disorders was ad-mittedtotheCriticalCareUnit(CCU)followingananteriorresectionformetastatic(lungandhepatic)adenocarcinoma of the sigmoid colon. Postopera-tivelythereweretwoinitialcomplications:first,anepisode of rectal bleeding from the anastomosissite, necessitating a return to theatre for explora-tion only; second, an episode of pulmonaryoedema, during which there were no prolongedperiods of hypoxaemia, and which resolved fol-lowing non-invasive continuous positive airwaypressureventilation.OnreturntoCCU,thepatientshowed no signs of delirium, was oriented intime, place and person, and was communicatingappropriately.Subsequently, eight hours after returning fromtheatre her Glasgow Coma Scale fell from 15 to 6(E1M4V1), with no obvious focal neurologicalabnormality. Blood tests (i.e. full blood profile,liver function tests, urea and electrolytes) andarterial blood gases revealed no cause for thisdeterioration.Accordingly, she was intubated andventilated, and a head CT scan was performedwhich revealed no apparent abnormalities toexplain her deterioration. She regained a full levelof consciousness the next day. Then, however, herlevel of consciousness progressively dropped overseveral hours. On examination, she kept her eye-lids clenched, and it was impossible to assess herpupils, which rolled backwards on manual eyelidretraction. Otherwise, cranial nerve examinationwas entirely normal, including a good gag reflex.Assessment of upper and lower limb neurologywas equally unremarkable with down-goingplantar responses.A Bi-Spectral (BIS) monitor (routinely used tomonitor intra-operative conscious levels) wasemployed to assess EEG activity and level of con-sciousness, as no electroencephalogram could beimmediately arranged. This demonstrated a bi-spectral index of 85–90, which is associated withwakefulness, and not any major intra-cerebralevent or convulsive activity.
Prognostic value of infranodal conduction time in patients with chronic bundle branch block.
Authors: M M Scheinman, R W Peters, G Modin, M Brennan, C Mies, J O'Young
Journal: Circulation (1977)

His bundle recordings were obtained in 121 patients with chronic bundle branch block and the patients were followed for a mean period of 18 months. Seventy-nine patients had an infranodal conduction time (H-Q) less than 70 msec while 42 had H-Q greater than or equal to 70 msec. There was no significant difference in mean age, smoking history, diabetes, syncope, dizziness, blood pressure, and serum cholesterol or triglyceride levels between the two groups. There was a significantly greater incidence of progresssion to second degree or third degree atrioventricular block (9/42, 21%), and of severe congestive heart failure (16/42, 38%) in patients with H-Q greater than or equal to 70 compared with those with H-Q less than 70 (1/79, 1.3%; and 13/79, 16%, respectively). The risk of sudden death was significantly greater only in the group with H-Q greater than or equal to 70 and severe congestive heart failure. There was no correlation between the presence of first degree atrioventricular block and/or any particular type of bundle branch block pattern with sudden death and/or progression to second degree or third degree atrioventricular block. Analysis of the surface electrocardiogram is only of limited value in predicting high risk patients with chronic bundle branch block. Electrophysiologic studies are of greatest value in patients with bundle branch block with transient neurologic symptoms in whom no cause for the symptoms is evident.
Immunological effects of stress in psoriasis
Authors: G. Schmid-Ott, B. Jaeger, T. Boehm, K. Langer, M. Stephan, U. Raap, T. Werfel
Journal: British Journal of Dermatology (2009)

Psychological stress causes phenotypic changes in circulating lymphocytes and is regarded as an important trigger of the Th1-polarized inflammatory skin disease psoriasis.To study the effects of psychological stress on immunological parameters, i.e. membrane molecules relevant to the pathophysiology of psoriasis, especially cutaneous lymphocyte-associated antigens (CLA) involved in T and natural killer (NK) cells homing in on the skin.The severity of psoriasis was assessed in patients using the Psoriasis Area and Severity Index. Patients with psoriasis (n=15) and healthy volunteers (n=15) were exposed to brief psychological stress in the laboratory. In vitro analyses were conducted 1 h before, immediately following and 1 h after stress exposure. Peripheral T- and NK-cell subsets including CD8+ T lymphocytes, CLA+ lymphocytes and lymphocyte function-associated antigen type 1 (LFA-1)+ lymphocytes were analysed by flow cytometry.We found a significant stress-induced increase of CD3+ T lymphocytes in patients with psoriasis only. Analyses of T-cell subsets revealed that this increase was observable for cytotoxic CD8+ T lymphocytes and CLA+ CD3+ lymphocytes. The total number of circulating NK cells (CD16+, CD56+) increased immediately after stress in both groups whereas only patients with psoriasis showed a significant increase in CLA+ NK cells.A higher stress-induced increase of CLA+ T and CLA+ NK cells in the circulation of patients with psoriasis might point to an increased ability of T and NK cells in the presence of psoriasis to home in on the skin during mental stress. Further studies are needed to verify these relationships in more detail and to investigate the time point at which these cells accumulate within lesional skin, and whether or not psychotherapy improves the quality of life of patients with psoriasis and influences stress-dependent parameters.
Of saving the elderly
Authors: C. Joyce
Journal: Journal of the Royal Society of Medicine (2007)

Dr Loefler's careful essay on the preferential treatment of children in matters of health (JRSM 2007;100:110-111)1 will by now have led to a great deal of argument, much of it emotional, polemic and unhelpful. A comparable analysis of attitudes to treatment at the end of life would surely be no less controversial. But, nevertheless, rather than seeking to lessen or abolish discrimination in favour of children, would the species not be better served by discriminating against the sick elderly, or—let us go the whole way—the elderly in general? Children do of course at first consume inordinate resources, to the cost of which they are initially unable to contribute. But the imbalance is quickly redressed in favour of their contributions when they cease to be children. This usually remains true for a long period until the balance turns once again against them. Then the disequilibrium becomes steadily more negative and, what is worse, has no predictable end.

The proposal may cause discomfort or appear out-rageous. But the taboo was partially broken long ago, with the introduction of Advance Directives and Do Not Resuscitate (DNR) orders. (A recent Google search produced over 500 000 references to DNR, almost 30 000 of them in association with the NHS.) Of course, many elderly people themselves come to conclude that their quality of life (and/or that of those around them) is no longer good enough to make their continuing existence worthwhile. If they continue to use up an increasing proportion of medical and paramedical resources that they no longer enjoy, should they not be allowed, or even encouraged, to dispense with them?
National survey of job satisfaction and retirement intentions among general practitioners in England
Authors: B. Sibbald
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives:</b> To measure general practitioners9 intentions to quit direct patient care, to assess changes between 1998 and 2000, and to investigate associated factors, notably job satisfaction. <b>Design:</b> Analysis of national postal surveys conducted in 1998 and 2001. <b>Setting:</b> England. <b>Participants:</b> 1949 general practitioner principals, of whom 790 were surveyed in 1998 and 1159 in 2001. <b>Main outcome measures:</b> Overall job satisfaction and likelihood of leaving direct patient care in the next five years. <b>Results:</b> The proportion of doctors intending to quit direct patient care in the next five years rose from 14% in 1998 to 22% in 2001. In both years, the main factors associated with an increased likelihood of quitting were older age and ethnic minority status. Higher job satisfaction and having children younger than 18 years were associated with a reduced likelihood of quitting. There were no significant differences in regression coefficients between 1998 and 2001, suggesting that the effect of factors influencing intentions to quit remained stable over time. The rise in intentions to quit was due mainly to a reduction in job satisfaction (1998 mean 4.64, 2001 mean 3.96) together with a slight increase in the proportion of doctors from ethnic minorities and in the mean age of doctors. Doctors9 personal and practice characteristics explained little of the variation in job satisfaction within or between years. <b>Conclusions:</b> Job satisfaction is an important factor underlying intention to quit, and attention to this aspect of doctors9 working lives may help to increase the supply of general practitioners. <h3>What is already known on this topic</h3> Early retirement is one of the factors contributing to a shortage of general practitioners in the NHS <h3>What this study adds</h3> The proportion of general practitioners intending to quit direct patient care within five years rose from 14% in 1998 to 22% in 2001 A decrease in overall job satisfaction is the most important factor underlying this rise Improving the quality of doctors9 working lives might help improve retention
Charcot-Marie-Tooth Disease Type 2A
Authors: Francesco Bombelli, Tanya Stojkovic, Odile Dubourg, Andoni Echaniz-Laguna, Sandrine Tardieu, Kathy Larcher, Patrizia Amati-Bonneau, Philippe Latour, Odile Vignal, Cécile Cazeneuve, Alexis Brice, Eric Leguern
Journal: JAMA Neurology (2014)

Axonal Charcot-Marie-Tooth disease (CMT) is genetically heterogeneous, with 11 genes identified. Axonal CMT has most frequently been associated with mutations in the MFN2 gene (CMT2A).To describe the clinical and molecular features of CMT2A, to delineate prognostic factors, to understand connections between a certain phenotype and more serious clinical consequences, and to identify interactions among the associated genes.We describe the clinical, molecular, electrophysiological, and additional features of 43 patients with CMT2A. The degree of physical disability was determined by the CMT neuropathy score and adapted to the CMT neuropathy score gradient to evaluate the clinical course. We evaluated all data within the context of the most recent and important publications concerning this issue.Twenty-five patients had early-onset CMT2A and severe functional disability, with 9 being wheelchair bound, and 18 had late-onset disease and a milder phenotype. Optic atrophy, vocal cord palsy, and auditory impairment were observed in 5, 6, and 2 patients, respectively. Among the 24 patients who underwent magnetic resonance imaging of the spinal cord, 6 had evidence of spinal atrophy with or without hydromyelia. In 1 patient, magnetic resonance imaging revealed hydrocephalus. Twenty different MFN2 mutations were identified, and 14 were considered new variants. Their transmission was predominantly autosomal dominant, with vertical transmission in 8 and de novo occurrence in 3. However, we also identified rare types of transmission, especially a germinal mosaicism and an autosomal recessive inheritance. One patient carried a rare variant in the GDAP1 gene and another in the OPA1 gene in association with MFN2 mutation.Charcot-Marie-Tooth disease type 2A associated with MFN2 mutations is clinically very heterogeneous. Ranging from a mild to a severe form, CMT2A exhibits various types of transmission. Optic atrophy and vocal cord palsy were observed in patients with severe disability and an early-onset form and also in patients with later onset. Hydromyelia and spinal cord atrophy support central nervous system involvement in CMT2A.
Psychiatric Aspects of Homicide Prevention
Authors: EMANUEL TANAY
Journal: American Journal of Psychiatry (1972)

The author describes three types of homicide: ego-syntonic, ego-dystonic, and psychotic. He points out that ego-dystonic, or dissociative, homicide is by far the most common and notes that it requires the presence of a number of factors: an overcontrolling superego in the perpetrator, a sadomasochistic relationship between victim and perpetrator, an altered state of consciousness, and the presence of a weapon. In his discussion of the difficulties inherent in developing methods of preventing homicidal behavior, the author points out that the one factor that could be controlled is the availability of the weapon, particularly guns.