tbuckley/cabot-search huggingface dataset:
Measuring the Severity of Injury
Authors: H B Stoner, D W Yates, D F Heath, K N Frayn
Journal: Journal of the Royal Society of Medicine (1980)

Attempts have been made to improve the Injury Severity Score (ISS) system of Baker et al. (1974) using plasma lactate data obtained from 277 patients shortly after injury and before treatment. The ISS is based on the Abbreviated Injury Scale (AIS) values of the individual injuries, being the sum of the squares of the values for the three most severely injured regions. Log (plasma lactate concentration) is positively related to ISS over its whole range. It was not possible to vary the AIS values, either on clinical grounds or using a computer, in such a way that the variance of the log (plasma lactate concentration) about its regression line with ISS was significantly reduced. With a score based on the sum of the squares of the AIS values for all the patient's injuries, some improvement to the AIS values could be made but it was not statistically significant. At the present time Baker's ISS method would seem to be the best way of grading injuries for acute studies.
BCR-ABL Messenger RNA Levels Continue to Decline in Patients with Chronic Phase Chronic Myeloid Leukemia Treated with Imatinib for More Than 5 Years and Approximately Half of All First-Line Treated Patients Have Stable Undetectable BCR-ABL Using Strict Sensitivity Criteria
Authors: Susan Branford, John F. Seymour, Andrew Grigg, Chris Arthur, Zbigniew Rudzki, Kevin Lynch, Timothy Hughes
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In the first years of imatinib treatment, BCR-ABL remained detectable in all but a small minority of patients with chronic myeloid leukemia. We determined whether BCR-ABL continues to decline with longer imatinib exposure and the incidence and consequence of undetectable BCR-ABL. Experimental Design: BCR-ABL levels were measured in a subset of 53 imatinib-treated IRIS trial patients for up to 7 years (29 first-line, 24 second-line). Levels were deemed undetectable using strict PCR sensitivity criteria. Results: By 18 months, the majority achieved a 3-log reduction [major molecular response (MMR)]. BCR-ABL continued to decline but at a slower rate (median time to 4-log reduction and undetectable BCR-ABL of 45 and 66 months for first-line). The probability of undetectable BCR-ABL increased considerably from 36 to 81 months of first-line imatinib {7% [95% confidence interval (95% CI), 0-17%] versus 52% (95% CI, 32-72%)}. Undetectable BCR-ABL was achieved in 18 of 53 patients and none of these 18 lost MMR after a median follow-up of 33 months. Conversely, MMR was lost in 6 of 22 (27%) patients with sustained detectable BCR-ABL and was associated with BCR-ABL mutations in 3 of 6. Loss of MMR was recently defined as suboptimal imatinib response. There was no difference in the probability of achieving molecular responses between first- and second-line patients but first-line had a significantly higher probability of maintaining MMR [P = 0.03; 96% (95% CI, 88-100%) versus 71% (95% CI, 48-93%)]. Conclusions: With prolonged therapy, BCR-ABL continued to decline in most patients and undetectable BCR-ABL was no longer a rare event. Loss of MMR was only observed in patients with sustained detectable BCR-ABL.
Detection, isolation, and functional characterization of two human T-cell subclasses bearing unique differentiation antigens.
Authors: R L Evans, J M Breard, H Lazarus, S F Schlossman, L Chess
Journal: The Journal of Experimental Medicine (1977)

A heterologous antihuman T-cell serum (anti-TH1), raised against purified peripheral T cells, and absorbed with an autologous Ig+ line, was shown to bind specifically to T- but not to B-lymphoid cells by both a complement-dependent cytotoxic assay and indirect immunofluorescence. Whereas 90% fetal thymocytes and thymocytes were killed by anti-TH1 and complement, a consistently restricted population (50-60%) of peripheral T cells from several normal donors were lysed, indicating that anti-TH1 is directed against one or more thymus-specific antigens which are lost or reduced on a subpopulation of human T cells in the periphery. Functional analysis of the unreactive (TH1-) and reactive (TH1+) T-cell subclasses demonstrated that TH1- cells mounted a good proliferative response to a battery of specific soluble antigens (mumps, PPD, tetanus toxoid) but neither responded in MLC, nor elaborated LMF in response to tetanus toxoid. In contrast TH1+ cells proliferated in MLC and elaborated LMF but did not respond by 3H-incorporation to soluble antigens. The relevance of these findings to human T-cell functions in vivo and to previously described functional subclasses of murine T cells is discussed.
Hypersensitivity to molybdenum as a possible trigger of ANA-negative systemic lupus erythematosus.
Authors: M Federmann, B Morell, G Graetz, M Wyss, P Elsner, R von Thiessen, B Wuthrich, D Grob
Journal: Annals of the Rheumatic Diseases (1994)

After implantation of two metal plates a 24 year old woman developed fever of unknown origin and successively more symptoms of an ANA-negative systemic lupus erythematosus (SLE). These symptoms resolved after removal of the plates and recurred during patch testing of the metal components, which showed a reaction to molybdenum. A lymphocyte transformation test indicated a delayed-type hypersensitivity to molybdenum. Subsequent progressive flare ups of SLE appeared without molybdenum reexposure. This is the first report suggesting the existence of a hypersensitivity to molybdenum, which may act as another environmental trigger for SLE.
An experimental evaluation of continuous normothermic, intermittent hypothermic, and intermittent normothermic coronary perfusion
Authors: A. H. Brown, M. V. Braimbridge, S. Darracott, J. Chayen, H. Kasap
Journal: Thorax (1974)

<b>Hedley Brown, A., Braimbridge, M. V., Darracott, Sally, Chayen, J., and Kasap, H. (1974).</b><i>Thorax</i>, <b>29</b>, 38-50. <b>An experimental evaluation of continuous normothermic, intermittent hypothermic, and intermittent normothermic coronary perfusion.</b> Coronary perfusion and hypothermia both have disadvantages, and excellent clinical results are obtained without them, though short operations, spontaneous cooling of unperfused hearts, hyperglycaemia, heparinization, and young and cyanotic subjects may allow more tolerance of ischaemia. Functional, macroscopic, histological, ultrastructural, chemical, and metabolic evidence of the inadvisability of ischaemia, especially of hypertrophied hearts, abounds, though statistical support and histochemical proof are lacking. Isovolumic function tests permit accurate assessment of compliance. Succinic dehydrogenase distribution is the most relevant enzyme assay of myocardial transport; freed phospholipids indicate cellular membrane disorganization. Adenosinetriphosphate response of myosin (myocardial ATP ase) is shown quantitatively by change of birefringence. Ventricular oedema may be detected by changes in weight. These tests were used to compare continuous normothermic, intermittent hypothermic, and intermittent normothermic perfusion over two hours in isolated, cross-perfused canine hearts. Isolated hearts are very sensitive to imperfections of maintenance, but cross-perfusion minimizes perfusion-induced deterioration. Normothermic continuously perfused hearts performed significantly better than intermittently perfused hearts, among which cooled hearts functioned better than normothermic hearts after two hours. Succinic dehydrogenase and acid haematein tests showed significant benefit from cooling during intermittent perfusion. The experimental preparation and techniques of assessment proved sensitive enough to demonstrate these differences, though cooling preserved cellular enzymes better than it did function. This work gives histochemical and statistical support to existing evidence that intermittent ischaemia for two hours can be ameliorated by moderate hypothermia but is not as effective for myocardial maintenance as constant perfusion with normal blood.
New Approaches and Therapeutics Targeting Apoptosis in Disease
Authors: Ute Fischer, Klaus Schulze-Osthoff
Journal: Pharmacological Reviews (2005)

Apoptosis, the major form of cellular suicide, is central to various physiological processes and the maintenance of homeostasis in multicellular organisms. Presumably, even more important is a causative or contributing role of apoptosis to various human diseases. These include situations with unwanted cell accumulation (cancer) and failure to eradicate aberrant cells (autoimmune diseases) or disorders with an inappropriate loss of cells (heart failure, stroke, AIDS, neurodegenerative diseases, and liver injury). The past decade has witnessed a tremendous progress in the knowledge of the molecular mechanisms that regulate apoptosis and the mediators that either prevent or trigger cell death. Consequently, apoptosis regulators have emerged as key targets for the design of therapeutic strategies aimed at modulating cellular life-and-death decisions. Numerous novel approaches are currently being followed employing gene therapy and antisense strategies, recombinant biologics, or classical organic and combinatorial chemistry to target specific apoptotic regulators. Convincing proof-of-principle evidence obtained in several animal models confirms the validity of strategies targeting apoptosis and revealed an enormous potential for therapeutic intervention in a variety of illnesses. Although numerous apoptotic drugs are currently being developed, several therapeutics have progressed to clinical testing or are already approved and marketed. Here we review the recent progress of apoptosis-based therapies and survey some highlights in a very promising field of drug development.
Prospective Study of Tardive Dyskinesia in the Elderly: Rates and Risk Factors
Authors: M G Woerner, J M Alvir, B L Saltz, J A Lieberman, J M Kane
Journal: American Journal of Psychiatry (1998)

Objective:The purposes of this study were to investigate the rate (incidence) of tardive dyskinesia in elderly patients beginning treatment with antipsychotic medication and to identify risk factors for development of tardive dyskinesia in this age group. Method:A group of 261 neuroleptic-naive patients aged 55 or above were identified at the time they were starting antipsychotic drug treatment. This group is the complete study group; a preliminary report based on the first 160 patients was published previously. Patients were evaluated at baseline and followed up at 3-month intervals for periods ranging from 3 to 393 weeks. Assessments included abnormal involuntary movements, extrapyramidal signs, psychiatric symptoms, and medical and drug treatment histories.Results:The cumulative rates of tardive dyskinesia were 25%, 34%, and 53% after 1, 2, and 3 years of cumulative antipsychotic treatment. A greater risk of tardive dyskinesia was associated with history of ECT treatment, higher mean daily and cumulative antipsychotic doses, and presence of extrapyramidal signs early in treatment. Differences in tardive dyskinesia rates between diagnostic groups found in univariate analyses were attenuated when the authors controlled for these variables.Conclusions:Tardive dyskinesia rates for patients beginning treatment with conventional antipsychotics in their fifth decade or later are three to five times what has been found for younger patients, despite treatment with lower doses. Alternative treatments need to be investigated. Am J Psychiatry 1998; 155: 1521-1528
Gene Therapy for Psychiatric Disorders
Authors: Robert M Sapolsky
Journal: American Journal of Psychiatry (2003)

There has been tremendous progress in developing techniques for manipulating genetic material, and the birth of gene therapy as a discipline has been one consequence of this. Most considerations of gene therapy in the nervous system have focused on attempts to transfer novel genes in for the purpose of protecting neurons from neurological insults. In this review, the author considers the progress in that field and the possible application of related gene therapy approaches to the far more difficult task of buffering against a psychiatric disorder. As an emphasis, the author reviews how the biology of psychiatric disorders is so often one of vulnerability to particular environments. Because of this context dependency, it would be likely that many possible gene therapeutic interventions would need to be context dependent as well. Thus, the author considers the plausibility of developing gene vector therapies that use conditional expression systems, in particular ones whose expression would be induced by the same environmental perturbations that exacerbate psychiatric symptoms themselves. In particular, the author considers the role of stress as a predisposing factor in certain psychiatric disorders and the ways in which stress signals can be harnessed as inducers of conditional expression systems in gene therapy.
Effect of stimulation of carotid chemoreceptors on total and regional cerebral blood flow.
Authors: D D Heistad, M L Marcus, J C Ehrhardt, F M Abboud
Journal: Circulation Research (1976)

This study was performed to determine whether stimulation of the carotid chemoreceptors increases total or regional cerebral blood flow and whether activation of arterial chemoreceptors contributes to cerebral vasodilation during systemic hypoxemia. In anesthetized and ventilated dogs, carotid chemoreceptors were stimulated with nicotine or hypoxic and hypercapnic blood. To measure total and regional cerebral blood flow, we used labeled 15-mu microspheres. Stimulation of chemoreceptors did not increase cerebral blood flow or produce significant redistribution of cerebral blood flow, even though the chemoreflex was intact in these animals (as manifested by vasoconstriction in muscle, kidney, and small bowel) and the cerebral vessels dilated in response to systemic hypercapnia. In other studies in anesthetized, ventilated dogs and rhesus monkeys, cerebral vasodilator responses to systemic hypoxemia were observed before and after denervation of carotid and aortic chemoreceptors. Systemic hypoxemia produced large and equivalent increases in cerebral blood flow before and after chemodenervation. We conclude that stimulation of carotid chemoreceptors does not produce cerebral vasodilation and that chemoreceptors do not contribute significantly to cerebral vasodilation during systemic hypoxemia.
Effect of incremental exercise on initiation and movement times in a choice response, whole body psychomotor task
Authors: T McMorris, S Delves, J Sproule, M Lauder, B Hale
Journal: British Journal of Sports Medicine (2005)

To examine how exercise at moderate and maximal intensities affects performance on a choice response time, whole body psychomotor task.Subjects (n = 12) were tested on a three-choice response time task, after rest and after exercise at 70% and 100% maximum power output (W*max). The dependent variables were time to begin forward momentum (initiation time) and time to complete the movement (movement time). Stride time for the first and second strides and number of strides to cover first 1.1 m were also measured. Blood lactate concentrations and heart rate were recorded before and after completion of each psychomotor test. The subjects subjectively assessed the amount of effort that they used to complete the task.Repeated measures analysis of variance showed a significant effect for initiation (F2,22 = 11.47, p < 0.001) and movement times (F2,22 = 14.61, p < 0.001). Post hoc least significant difference (LSD) tests showed that initiation time after exercise at 70% W*max was significantly faster than that in the other two conditions. Speed of initiation after rest was significantly quicker than that after exercise at W*max. For movement time, LSD tests showed that time after maximal exercise was significantly slower than that in the other two conditions. Stride time for the second stride showed a significant effect (F2,22 = 6.20, p < 0.01). LSD tests found that time after exercise at W*max was significantly slower in the other two conditions. Stepwise multiple regression analyses found that the increment of change, from rest, of lactate concentrations could significantly predict the increment of change in initiation (R2 = 0.40) and movement (R2 = 0.50) times.Exercise affects a whole body task differently from purely cognitive tasks. Central factors are probably more important than peripheral factors.
Diagnosing airflow obstruction in general practice
Authors: K. JONES
Journal: Thorax (1999)

A decade ago several research studies highlighted the underdiagnosis of asthma, particularly in children1-3 but also in the elderly,4 5 and most general practitioners felt an increased pressure on them to diagnose this common chronic respiratory disorder. It was implied that asthma should be considered whenever a patient presented with a persistent cough and that far more people “deserved” to be on effective treatment with inhaled steroids. Undoubtedly, as a consequence of this message, many with asthma gained treatment which otherwise would not have been provided and, presumably, improved their morbidity and quality of life.

However, there has emerged a down side to this campaign in that some subjects with other respiratory conditions and some with no lung disease at all have been labelled as having asthma, leading not only to years of receiving unnecessary medication but also to the development of psychological dependence on the asthma label and its associated quest for improvements in symptom control. Most of such subjects have chronic obstructive pulmonary disease (COPD), but in my clinical practice I have also found cases of hyperventilation, recrudescent tuberculosis, and severe sleep apnoea …
Ileitis after colectomy for ulcerative colitis or carcinoma.
Authors: A Hallak, M Baratz, M Santo, Z Halpern, M Rabau, N Werbin, T Gilat
Journal: Gut (1994)

An ileitis developing years or months after ileostomy was recognised and described many years ago but has rarely been mentioned since. We describe nine patients with a non-specific preanastomotic ileitis that developed years after colectomy in patients operated on for ulcerative colitis or carcinoma. The disease developed after various types of reconstruction: ileorectal, ileoanal, with or without pouch. The diseased ileum showed inflammation, erosions, ulcerations, and sometimes strictures. The disease course ranged from asymptomatic to severe pain and diarrhoea. No specific cause could be shown. Granulomas, infectious agents or ischaemic changes were not found. The anastomosis was always patent. Three patients have had numerous episodes of intestinal obstruction presumably because of adhesions. Seven of nine patients were female. The response to steroids, 5-aminosalicylic acid preparations, and methotrexate was poor, three patients responded well to azathioprine. The condition is not rare and the cause remains unknown.
BT-07 * MEASURING TUMOR METABOLISM IN DIFFUSE INTRINSIC PONTINE GIOMAS (DIPG) USING HYPERPOLARIZED CARBON-13 MR SPECTROSCOPIC IMAGING
Authors: I. Park, R. Hashizume, X. Yang, P. Larson, C. D. James, D. Vigneron, S. Mueller, S. Nelson
Journal: Neuro-Oncology (2015)

Diffuse intrinsic pontine gliomas (DIPGs) continue to have a very poor prognosis with a median survival rate of 9 months. The methods for assessing treatment response and tumor progression are based on radiographic response but conventional MRI is not sufficient for predicting clinical outcome. A recent first-in-human study using hyperpolarized 13C MR metabolic imaging showed the safety and feasibility of this technology for evaluating hyperpolarized pyruvate metabolism in humans. The purpose of this study was to demonstrate the feasibility of using hyperpolarized 13C metabolic imaging with [1-13C]pyruvate as a non-invasive imaging tool to evaluate in vivo metabolism in orthotopic brainstem xenografts injected with human DIPG cells. Primary human derived DIPG cells were implanted into the brainstem of athymic rats (n = 4). 3D magnetic resonance spectroscopic imaging (MRSI) data were acquired using a clinical 3T scanner with a custom-designed 1H/13C coil after the injection of hyperpolarized [1-13C]pyruvate solution. The hyperpolarized 13C MRSI data exhibited an abnormal 13C metabolism in the T2 lesions. The mean normalized lactate, normalized pyruvate and the ratio of lactate to pyruvate in the T2 hyperintense voxels were 3.1 ± 1.7, 1.5 ± 0.4 and 0.47 ± 0.2 (mean ± standard deviation), respectively, and significantly higher than the corresponding values from the contra-lateral hemisphere. The lactate signal in theses areas were highly elevated compared to the lactate signal in the normal appearing brain tissue from the supratentorial region. The metabolite quantification revealed the differentiation of lactate signal between tumor core, tissue in the periphery of tumor and tissue in the contra-lateral hemisphere. The corresponding H&E stained slides showed viable tumor that recapitulated the histopathology of a subset of high-grade pediatric astrocytomas. The results suggest that this technique may provide a unique non-invasive imaging tool that will be beneficial in the management of patients with DIPG.
Transbronchial biopsy as a tool to evaluate small airways in asthma
Authors: S. Balzar, S.E. Wenzel, H.W. Chu
Journal: European Respiratory Journal (2002)

Small airway (SA) inflammation in asthmatics is poorly understood. Surgical biopsies to obtain peripheral lung tissue are seldom justified in asthmatics. Therefore, the authors hypothesised that transbronchial biopsy could be an alternative approach to evaluate SA in asthma. Transbronchial and endobronchial biopsy tissue samples (TBBX and EBBX) from 12 severe asthmatics were evaluated for airway and parenchymal total inflammatory cell count expressed as the sum of immunostained T‐cells (CD3), macrophages (CD68), mast cells (tryptase AA1), neutrophils (neutrophil elastase) and eosinophils (EG2) per mm 2 . The large airways (LA) were evaluated in EBBXs, while SA, medium airways (MA) and alveolar tissue (AT) were evaluated in TBBXs. When cell counts from SA, MA, LA and AT were compared, SA had a significantly higher cell count than MA or LA (SA 1011·mm −2 (539–1,290), MA 346·mm −2 (223–415), LA 332·mm −2 (189–416), AT 464·mm −2 (298–834)). The cell density and pattern of the inflammatory cell distribution in subjects with TBBXs appeared similar to those in three severe asthmatics whose inflammatory cells were analysed in surgical tissue samples. This study suggests that small airway may be identified and analysed in transbronchial biopsy tissue samples and therefore transbronchial biopsy tissue samples could expand the analysis of inflammation and tissue remodelling in asthma.