tbuckley/cabot-search huggingface dataset:
Clinical, microbiological, and immunological studies in patients with immunoglobulin deficiencies and gastrointestinal disorders
Authors: W. R. Brown, D. Butterfield, D. Savage, T. Tada
Journal: Gut (1972)

Seven patients with gastrointestinal disorders and deficiencies of serum and secretory immunoglobulins were evaluated clinically, microbiologically, and immunologically. Five patients had generalized deficiencies of immunoglobulins; two were selectively deficient. Diarrhoea and malabsorption in six of the seven patients were at least partially explained. Four of the five patients with generalized hypogammaglobulinaemia had intestinal infestation with Giardia lamblia; in three of the five, excessive numbers of anaerobic bacteria were cultured from small bowel fluids. Despite much variability in relative severity of patients' respiratory and gastrointestinal tract symptoms, deficiencies of mucosal immunocytes and immunoglobulins in nasopharyngeal and gastrointestinal tract tissues and secretions were similar. Except for one selectively IgA-deficient patient, all patients were deficient in IgE. The study characterizes in greater detail than heretofore the gastrointestinal disorders associated with immunoglobulin deficiency states.
Healthcare workers’ role in keeping MMR vaccination uptake high in Europe: a review of evidence
Authors: B Simone, P Carrillo-Santisteve, P L Lopalco
Journal: Eurosurveillance (2012)

Measles is a highly contagious and potentially fatal disease. Europe is far from the 95% coverage rates necessary for elimination of the disease, although a safe and cost-effective vaccine is available. We reviewed the literature on studies carried out in European countries from January 1991 to September 2011 on knowledge, attitudes and practices of health professionals towards measles vaccination and on how health professionals have an impact on parental vaccination choices. Both quantitative and qualitative studies were considered: a total of 28 eligible articles were retrieved. Healthcare workers are considered by parents as a primary and trustworthy source of information on childhood vaccination. Gaps in knowledge and poor communication from healthcare workers are detrimental to high immunisation rates. Correct and transparent information for parents plays a key role in parental decisions on whether to have their children vaccinated. Healthcare workers' knowledge of and positive attitudes towards measles-mumps-rubella (MMR) vaccination are crucial to meeting the measles elimination goal. An effort should be made to overcome potential communication barriers and to strengthen vaccine education among healthcare professionals.
Movement planning and movement execution: What is in between?
Authors: N. Dounskaia, G. E. Stelmach
Journal: Behavioral and Brain Sciences (2001)

Although the model proposed by Thelen and co-authors provides a detailed explanation for the processes underlying reaching, many aspects of it are highly speculative. One of the reasons for this is our lack of knowledge about transformation of a hand movement plan into joint movements. The leading joint hypothesis (LJH) allows us to partially fill in this gap. The LJH offers a possible explanation for the formation of movement and how it may be represented in memory. Our explanation converges with the dynamic model described in the target article.
Depletion of Methionine Aminopeptidase 2 Does Not Alter Cell Response to Fumagillin or Bengamides
Authors: Sunkyu Kim, Kenneth LaMontagne, Michael Sabio, Sushil Sharma, Richard W. Versace, Naeem Yusuff, Penny E. Phillips
Journal: Cancer Research (2004)

Inhibition of endothelial cell growth by fumagillin has been assumed to be mediated by inhibition of the molecular target methionine aminopeptidase 2 (MetAp2). New data show that depletion of MetAp2 by siRNA does not inhibit endothelial cell growth. Moreover, MetAp2-depleted endothelial cells remain responsive to inhibition by either fumagillin or a newly identified MetAp2 enzyme inhibitor. These data suggest that MetAp2 function is not required for endothelial cell proliferation.
Prone position reduces lung stress and strain in severe acute respiratory distress syndrome
Authors: S. D. Mentzelopoulos, C. Roussos, S. G. Zakynthinos
Journal: European Respiratory Journal (2005)

The present authors hypothesised that in severe acute respiratory distress syndrome (ARDS), pronation may reduce ventilator-induced overall stress (i.e. transpulmonary pressure (P(L))) and strain of lung parenchyma (i.e. tidal volume (V(T))/end-expiratory lung volume (EELV) ratio), which constitute major ventilator-induced lung injury determinants. The authors sought to determine whether potential pronation benefits are maintained in post-prone semirecumbent (SR(PP)) posture under pressure-volume curve-dependent optimisation of positive end-expiratory pressure (PEEP). A total of 10 anesthetised/paralysed, mechanically ventilated (V(T) = 9.0+/-0.9 mL.kg(-1) predicted body weight; flow = 0.91+/-0.04 L.s(-1); PEEP = 9.4+/-1.3 cmH(2)O) patients with early/severe ARDS were studied in pre-prone semirecumbent (SR(BAS)), prone, and SR(PP) positions. Partitioned respiratory mechanics were determined during iso-flow (0.91 L.s(-1)) experiments (V(T) varied within 0.2-1.0 L), along with haemodynamics, gas exchange, and EELV. Compared with SR(BAS), pronation/SR(PP) resulted in reduced peak/plateau P(L) at V(T)s> or =0.6 L; static lung elastance and additional lung resistance decreased and chest wall elastance (in prone position) increased; EELV increased (23-33%); V(T)/EELV decreased (27-33%); arterial oxygen tension/inspiratory oxygen fraction and arterial carbon dioxide tension improved (21-43/10-14%, respectively), and shunt fraction/physiological dead space decreased (21-50/20-47%, respectively). In early/severe acute respiratory distress syndrome, pronation under positive end-expiratory pressure optimisation may reduce ventilator-induced lung injury risk. Pronation benefits may be maintained in post-prone semirecumbent position.
Cytokine expression in bronchial biopsies of cystic fibrosis patients with and without acute exacerbation
Authors: C Wojnarowski, T Frischer, E Hofbauer, C Grabner, W Mosgoeller, I Eichler, R Ziesche
Journal: European Respiratory Journal (1999)

In patients with cystic fibrosis (CF), the progression of pulmonary disease differs considerably, even in identical cystic fibrosis transmembrane conductance regulator-genotypes which could reflect an additional influence of the host's immune response. This study therefore measured cytokine expression patterns in CF patients with different clinical presentation. Expression of interleukin (IL)-8, interferon gamma (IFN-gamma), IL-4, IL-10, and transforming growth factor (TGF)beta(I) was assessed in bronchial mucosal biopsies of eight CF patients with acute exacerbation (age 6.0-14.2 yrs), eight CF patients with chronic stable disease (age 7.3-17.4 yrs), and in five normal control subjects by semiquantitative and quantitative reverse transcriptase polymerase chain reaction combined with histopathological assessment and immunohistochemical staining. All CF patients expressed IL-8. In acute exacerbation, expression of TGF-beta1 and IFN-gamma was either absent or extremely low. In contrast, all patients with stable disease strongly expressed TGF-beta1. The highest expression of TGF-beta1 and IFN-gamma was found in CF patients with mild disease and a history of infrequent exacerbations. No correlation was found between the expression of IL-4 and IL-10 and patient history. In normal control subjects, only a weak expression of TGF-beta1 was observed. These results show a remarkable correlation between cytokine pattern and the clinical course of cystic fibrosis. High expression of transforming growth factor-beta1 and interferon gamma was associated with mild disease, whereas no or very weak expression of these cytokines was typical for patients with acute disease and frequent exacerbations suggesting a contribution of the immune response to the progression of pulmonary disease in cystic fibrosis.
Randomised controlled trial of brief psychological intervention after deliberate self poisoning Commentary: Another kind of talk that works?
Authors: E. Guthrie, N. Kapur, K. Mackway-Jones, C. Chew-Graham, J. Moorey, E. Mendel, F. Marino-Francis, S. Sanderson, C. Turpin, G. Boddy, B. Tomenson, G. C Patton
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To determine the effects of a brief psychological intervention (brief psychodynamic interpersonal therapy) for patients after deliberate self poisoning compared with usual treatment. To compare the impact of the active intervention and usual treatment on patients9 satisfaction with care. <b>Design:</b> Randomised controlled trial. <b>Participants:</b> 119 adults who had deliberately poisoned themselves and presented to the emergency department of a teaching hospital. <b>Setting:</b> Community based study. <b>Intervention:</b> Four sessions of therapy delivered in the patient9s home. Control patients received "treatment as usual," which in most cases consisted of referral back to their general practitioner. <b>Outcome measures:</b> Severity of suicidal ideation six months after treatment as assessed by the Beck scale for suicidal ideation. Secondary outcome measures at six month follow up included depressive symptoms as measured by the Beck depression inventory, patient satisfaction with treatment, and self reported subsequent attempts at self harm. <b>Results:</b> Participants randomised to the intervention had a significantly greater reduction in suicidal ideation at six month follow up compared with those in the control group (reduction in the mean (SD) Beck scale 8.0 <i>v</i> 1.5). They were more satisfied with their treatment and were less likely to report repeated attempts to harm themselves at follow up (proportion repeating 9% <i>v</i> 28% in control group; difference 19%, 95% confidence interval 9% to 30 %, P=0.009). <b>Conclusion:</b> Brief psychodynamic interpersonal therapy may be a valuable treatment after people have deliberately tried to poison themselves. <h3>What is already known on this topic</h3> Deliberate self poisoning is one of the commonest reasons for admission to hospital in the United Kingdom and up to 15% of patients who poison themselves eventually kill themselves There are no interventions of proved efficacy for these patients Most episodes of self poisoning are precipitated by some form of interpersonal problem <h3>What this study adds</h3> Compared with usual treatment four sessions of psychodynamic interpersonal therapy reduced suicidal ideation and self reported attempts at self harm The intervention also improved patients9 satisfaction with care
The case of the missing brain: Arguments for a role of brain-to-spinal cord pathways in pain facilitation
Authors: Linda R. Watkins, Steven F. Maier
Journal: Behavioral and Brain Sciences (1997)

This commentary on coderre &amp; katz, wiesenfeld-hallin et al., and dickenson focuses on: (a) the brain as an under-recognized contributor to pain facilitation at the spinal cord; (b) these brain-to-spinal pathways being activated by learning or by body infection/inflammation; and (c) the resultant spinal release of anti-analgesic neuropeptides, activators of the NMDA-NO cascade, and activators of glia.
Epigenomics of Idiopathic Pulmonary Fibrosis
Authors: Einat I. Rabinovich, Moisés Selman, Naftali Kaminski
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

In this study, using sLC and CD11b-DTR techniques, monocytes were depleted from both peripheral blood by 70-95% and spleen by 50-70%.Administration of MC21 mAb removed 45% of the PBMs.Whether or not the three techniques have an influence on monocytes and neutrophils in the bone marrow was not reported.It is crucial to cautiously choose depletion strategies because monocytes are able to migrate among different pools (the peripheral blood, spleen, and bone marrow) during inflammation.Monocytes also play a requisite role in regulating the resolution of inflammation by different mechanisms.Otherwise, it is very difficult to interpret the experimental findings.This notion is supported by the following findings: (1) bone marrow can release Ly6C high CCR2 1 monocytes to the blood stream in response to the LPS challenge ( 12); (2) the spleen is a storage site that contains 50% of monocytes (Ly6C high ) in the body, and splenic monocytes can be rapidly mobilized toward the peripheral blood and inflamed site during inflammation and injury (13); (3) the splenic monocytes are indispensable elements forming immune reflex, which controls production of systemic proinflammatory cytokines (for example, TNF-a) ( 14) through the cholinergic-a7nAChR pathway; (4) alternatively activated monocytes (M2) in the peripheral blood and spleen might be involved in the resolution of inflammation (15); and (5) activation of CD11b in monocytes is able to limit TLR4dependent proinflammatory cytokine production ( 16).Alveolar flooding is a hallmark of ALI and ARDS.It should be mentioned that the magnitude of lung injury in this study is not equivalent to the clinical conditions because the dosages of LPS (0.4 mg/kg) and bacteria (10 25 cfu) used in the experiments were relatively low.In the meantime, a clear link among PBM depletion, alveolar neutrophilia, and pulmonary edema has not been established.Alveolar neutrophilia and the slight increase of lung vascular permeability are not parallel to the formation of pulmonary edema.Therefore, the conclusion drawn from the current study should be verified in more severe conditions and the other ALI animal models that are neutrophil dependent, for example, acid aspiration, transfusion-related acute lung injury, and ventilator-induced lung injury.Nevertheless, this study contributes importantly to ongoing research on how neutrophils are guided to the airspaces of the lung to mediate lung inflammation and injury.
Fyn and Src Are Effectors of Oncogenic Epidermal Growth Factor Receptor Signaling in Glioblastoma Patients
Authors: Kan V. Lu, Shaojun Zhu, Anna Cvrljevic, Tiffany T. Huang, Shawn Sarkaria, David Ahkavan, Julie Dang, Eduard B. Dinca, Seema B. Plaisier, Isaac Oderberg, Yohan Lee, Zugen Chen, Jeremy S. Caldwell, Yongmin Xie, Joseph A. Loo, David Seligson, Arnab Chakravari, Francis Y. Lee, Roberto Weinmann, Timothy F. Cloughesy, Stanley F. Nelson, Gabriele Bergers, Thomas Graeber, Frank B. Furnari, C. David James, Webster K. Cavenee, Terrance G. Johns, Paul S. Mischel
Journal: Cancer Research (2009)

Abstract Activating epidermal growth factor receptor (EGFR) mutations are common in many cancers including glioblastoma. However, clinical responses to EGFR inhibitors are infrequent and short-lived. We show that the Src family kinases (SFK) Fyn and Src are effectors of oncogenic EGFR signaling, enhancing invasion and tumor cell survival in vivo. Expression of a constitutively active EGFR mutant, EGFRvIII, resulted in activating phosphorylation and physical association with Src and Fyn, promoting tumor growth and motility. Gene silencing of Fyn and Src limited EGFR- and EGFRvIII-dependent tumor cell motility. The SFK inhibitor dasatinib inhibited invasion, promoted tumor regression, and induced apoptosis in vivo, significantly prolonging survival of an orthotopic glioblastoma model expressing endogenous EGFRvIII. Dasatinib enhanced the efficacy of an anti-EGFR monoclonal antibody (mAb 806) in vivo, further limiting tumor growth and extending survival. Examination of a large cohort of clinical samples showed frequent coactivation of EGFR and SFKs in glioblastoma patients. These results establish a mechanism linking EGFR signaling with Fyn and Src activation to promote tumor progression and invasion in vivo and provide rationale for combined anti-EGFR and anti-SFK targeted therapies. [Cancer Res 2009;69(17):6889–98]
Can nocturnal emergency surgery be reduced?
Authors: D J Sherlock, J Randle, M Playforth, R Cox, R T Holl-Allen
Journal: BMJ (1984)

A prospective study of emergency operations was performed over three months in a district general hospital. Before starting surgery surgeons completed a questionnaire recording clinical details together with time of admission and were asked to state whether in their opinion the case could be safely deferred until the next morning assuming operating time was available. Of 251 operations performed, forms were completed for 244. According to the surgeons, 62 could have been safely deferred, and subsequent independent analysis indicated a further 24 could also have been safely postponed, giving a total of 86 cases (35%). Of the remainder, 71 were started between 2300 and 0900, and of these 51 (71%) were major operations requiring an experienced surgeon. The results suggest that, although the volume of nocturnal major surgery could not be reduced, the introduction of a daily emergency theatre session for cases seen during the day and those which could be deferred from the previous night would appreciably reduce the overall workload of nocturnal surgery at present done by the resident junior staff. This study will have important implications if, as has been suggested, the number of junior medical staff on call at night for emergencies is reduced.
A Quantitative Measurement of the Human Somatic Mutation Rate
Authors: David J. Araten, David W. Golde, Rong H. Zhang, Howard T. Thaler, Lucia Gargiulo, Rosario Notaro, Lucio Luzzatto
Journal: Cancer Research (2005)

Abstract The mutation rate (μ) is a key biological feature of somatic cells that determines risk for malignant transformation, and it has been exceedingly difficult to measure in human cells. For this purpose, a potential sentinel is the X-linked PIG-A gene, because its inactivation causes lack of glycosylphosphatidylinositol-linked membrane proteins. We previously found that the frequency (f) of PIG-A mutant cells can be measured accurately by flow cytometry, even when f is very low. Here we measure both f and μ by culturing B-lymphoblastoid cell lines and first eliminating preexisting PIG-A mutants by flow sorting. After expansion in culture, the frequency of new mutants is determined by flow cytometry using antibodies specific for glycosylphosphatidylinositol-linked proteins (e.g., CD48, CD55, and CD59). The mutation rate is then calculated by the formula μ = f/d, where d is the number of cell divisions occurring in culture. The mean μ in cells from normal donors was 10.6 × 10−7 mutations per cell division (range 2.4 to 29.6 × 10−7). The mean μ was elevated &amp;gt;30-fold in cells from patients with Fanconi anemia (P &amp;lt; 0.0001), and μ varied widely in ataxia-telangiectasia with a mean 4-fold elevation (P = 0.002). In contrast, μ was not significantly different from normal in cells from patients with Nijmegen breakage syndrome. Differences in μ could not be attributed to variations in plating efficiency. The mutation rate in man can now be measured routinely in B-lymphoblastoid cell lines, and it is elevated in cancer predisposition syndromes. This system should be useful in evaluating cancer risk and in the design of preventive strategies.
Azlocillin, Mezlocillin, and Piperacillin: New Broad-Spectrum Penicillins
Authors: GEORGE M. ELIOPOULOS
Journal: Annals of Internal Medicine (1982)

Three new broad-spectrum penicillins—azlocillin, mezlocillin, and piperacillin—will soon be available for clinical use. Azlocillin and piperacillin are more active than carbenicillin or ticarcillin against Pseudomonas aeruginosa. Piperacillin and mezlocillin demonstrate significant activity against the Enterobacteriaceae, including many strains of Klebsiella pneumoniae against which the older penicillins carbenicillin, ticarcillin, and ampicillin are ineffective. All three new drugs show substantial activity against anaerobes and ampicillinsusceptible gonococci and Haemophilus influenzae. Because these agents are inactivated by various betalactamases, most Staphylococcus aureus isolates and a number of gram-negative organisms, including some important nosocomial pathogens, will be resistant to these antibiotics. The new penicillins appear to be relatively safe and have been used successfully to treat patients with various infections; however, comparative trials have not yet established the superiority of these drugs over conventional therapeutic agents.
Prosthetic Mitral Valve Thrombosis: Can Fluoroscopy Predict the Efficacy of Thrombolytic Treatment?
Authors: Piero Montorsi, Dario Cavoretto, Marina Alimento, Manuela Muratori, Mauro Pepi
Journal: Circulation (2003)

Background Thrombolysis (T) is an effective therapy for prosthetic valve thrombosis (PVT). Debate still exists as to which clinical or noninvasive finding best predict the result of T. The aim of the study was to investigate the role of fluoroscopy (F) to predict efficacy of T in pts with mitral PVT. Methods We evaluated 17 consecutive pts with bileaflet mitral PVT. F criteria for PVT were: abnormal disc motion and calculated opening angle &gt;25°. T was carried out with tissue-type plasminogen activator (tPA; 100 mg over 3 hours followed by heparin infusion for 24 hours) and was considered successful when normalization of leaflet motion and opening angle occurred. Results were evaluated according to symptom duration (&lt;21 days, early PVT; &gt;21 days, late PVT) and to F pattern of PVT (blocked leaflet versus hypomobile leaflet). Results F showed disc motion alteration in 24 of 34 leaflets: 8 leaflets were blocked, whereas 16 were hypomobile. Early (12.7±6.1 days, range 3–21) and late (113±114 days, range 28–365) PVT was present in 8 and 7 pts, respectively. Thrombolysis was successful in 20 of 24 leaflets. Blocked leaflet fully recovered only in early PVT (n=4) pts, whereas they remained blocked in late PVT (n=4). On the contrary, in all of the cases with hypomobile leaflet, disc motion normalized regardless duration of symptoms and extent of disc motion reduction. Interestingly, 4 leaflets with late PVT was diagnosed as blocked by trans-thoracic (TTE). F showed a residual disc movement in all: they fully recovered after T. Two pts with late PVT had both leaflets affected (1 blocked +1 hypomobile); although blocked leaflet did not respond to T, the normalization of hypomobile significantly improved clinical condition. Conclusions F can predict result of T in mitral PVT. PVT with F evidence of hypomobile leaflet always recovers regardless of symptom duration and extent of disc motion reduction, suggesting that the small amount of thrombus needed to interfere with discs motion in bileaflet prostheses remains sensitive to T even after a long time. PVT with F evidence of blocked leaflet has a favorable response to T only in case of early PVT. Late PVT with blocked leaflet does not respond to T, suggesting a larger and stratified thrombus and the coexistence of pannus and, in our series, always required surgery. However, if a hypomobile leaflet coexists, T may be used to restore normal movement of hypomobile leaflet so that to improve patient clinical and hemodynamic condition before operation.