tbuckley/cabot-search huggingface dataset:
NI-32 * ENHANCING TUMOR RESPONSE USING QUANTITATIVE VOLUMETRY FROM T1 SUBTRACTION MAPS IN MALIGNANT GLIOMA TREATED WITH DENDRITIC CELL VACCINATION
Authors: A. Hardy, R. Prins, X. Kong, D. Woodworth, W. Pope, W. Yong, T. Cloughesy, L. Liau, B. Ellingson
Journal: Neuro-Oncology (2014)

PURPOSE: To ascertain the radiologic response and serial volumetric changes in patients with glioblastoma multiforme (GBM) treated with dendritic cell (DC) vaccine using contrast enhanced (CE) T1-weighted subtraction maps. METHODS: MR images were acquired for fourteen patients with newly diagnosed or recurrent GBM. Genetic analyses and intratumoral histopathology were performed on all but one patient. Changes in CE tumor volumes were assessed with CE T1-weighted subtraction maps generated via voxel-wise subtraction of Gaussian-normalized signal intensities T1-weighted and CE T1-weighted images. Response criterion was determined as 25% reduction in the T1 subtraction CE tumor volume with respect to pre-vaccination baseline. Response stratification was tested as a predictor of PFS using log-rank univariate analysis. RESULTS: Four patients responded to the treatment within the first three months of treatment. Ten patients did not respond within the same period of time. One patient exhibited a growth pattern consistent with pseudo-progression between 100 and 300 days after vaccination. A significant difference in tumor growth rate (P = 0.0064) months between responders and non-responders was found within the first three months via linear regression. A preference for unfavorable response in MGMT unmethylated, EGFR amplified, and EGFRVIII mutated tumors, and favorable response in IDH1 mutant tumors was observed. A significantly longer PFS was found both from the opening date of the trial for each patient (Log-rank, P = 0.0149) and from the date of first vaccination (Log-rank, P = 0.0440) for responders versus non-responders. CONCLUSION: The clinical utility of T1 subtraction maps for tumor visualization and burden evaluation was shown. Response outcomes to DC vaccine therapy become apparent within the first three months of following treatment. Mischaracterization of pseudo-progression in the context of DC vaccine therapy for malignant glioma may not be a major concern. Genetic analyses and histopathological considerations may be a component in assessing treatment response to immunotherapy in malignant gliomas.
Abstract 5602: Identification of ethnic specific differences in breast cancer and normal breast tissue
Authors: Lisa L. Baumbach, Carmen Gomez, Jim Yan, Tom Halsey, Mary Ellen Ahearn, Merce Jorda, Mark Pegram
Journal: Cancer Research (2011)

Abstract Disparities in breast cancer stage of presentation and survival rates exist in patients of different ethnicities. These differences are undoubtedly a result of a combination of factors, including socio-economic, lifestyle, tumor characteristics and inherent factors, such as genetic composition. Our group is analyzing the genetic contributions to these disparities, with the goal to increase understanding of the underlying biology, leading ultimately to individualized, ethnic-specific diagnostic and therapeutic approaches. Here we report our results of a recently completed study focusing on gene expression profiling in a multi-ethnic cohort of triple negative breast cancer patients. We analyzed breast cancer and self-matched normal tissue samples from 10 African-American (AA), 10 Hispanic (His), and 10 non-Hispanic white (Caucasian) patients from south Florida. Study samples were cut from FFPE (Formalin Fixed Paraffin-embedded tissue) blocks marked by pathology as normal vs. tumor tissue, and sent to Almac Diagnostics for RNA isolation, cDNA preparation, and hybridization of tumor/normal cDNAs to a breast cancer focused gene expression array (Breast Cancer DSA Research Tool). From the Breast Cancer DSA arrays data, a two-way ANOVA (disease state and ethnicity) was used to identify transcripts with a p-value less than 0.01. Data QC indicated that samples clustered well with respect to ethnicity and adjacent normal vs. tumor tissue. We have identified ethnic-specific expression patterns in the matched normal and tumor samples. Initial pathway analysis using MetaCore Program shows that a number of genes related to the DNA repair pathway are differentially expressed across the ethnicities. In a set of ten DNA repair/cell cycle genes, the direction of change (increased or decreased expression) was the same for all three ethnic groups, however, the level of change differed greatly between ethnic groups. Fold change in this set of ten genes ranged from -6.54 to +5.53 with all being greater than 2 fold change in at least one ethnic group. Additional pathway analysis and validation of these results is ongoing. In follow up to this study, we have initiated parallel analysis in normal tissue samples (reduction mammoplasty) samples from AA and Cau non-cancer patients. Combined analysis of tumor and normal expression data will help to better understand the possible significance of gene expression differences in breast tissue between ethnic groups. These studies have important implications for addressing BC health disparities, as well as tailored approaches to prediction, prevention and treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5602. doi:10.1158/1538-7445.AM2011-5602
Cutaneous Myiasis of the Eyelid due to Cuterebra Larva
Authors: Martin S. Cogen
Journal: JAMA (1987)

HUMAN myiasis is the invasion of the body tissues of man by larvae of flies of the order Diptera. The disease occurs worldwide and many species of flies are involved.<sup>1</sup>Occurrence in the United States is infrequent, and human myiasis caused by the highly host-specific botflies is rare.<sup>2</sup>We report a case of dermal botfly myiasis of the eyelid due to a<i>Cuterebra</i>larva, which developed after an apparent insect bite occurring remotely over the ipsilateral clavicle. We emphasize the importance of differentiating this condition from the bacterial furuncle that it closely resembles. <h3>Report of a Case</h3> A 28-year-old man was initially seen with a three-week history of a swollen, tender nodule on his right upper eyelid. The patient, who worked as a lumberjack, had no recent history of travel outside the state of Alabama. The patient stated that two weeks before the onset of symptoms, he was
An out-patient nutritional supplementation programme in COPD patients
Authors: MK Sridhar, A Galloway, ME Lean, SW Banham
Journal: European Respiratory Journal (1994)

Studies that have assessed the role of nutritional supplementation in patients with emphysematous chronic obstructive pulmonary disease (COPD) have shown conflicting results. Improved respiratory muscle strength and exercise capacity have been demonstrated following intensive and costly nutritional support programmes under controlled conditions. We have evaluated a simple programme of out-patient nutritional support in a clinical setting. Twelve malnourished COPD patients (9 male and 3 female; mean age 66 yrs; &lt; 90% ideal body weight) were studied. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), estimation of maximal oxygen uptake (VO2max) during exercise, respiratory muscle strength (PImax and PEmax), and measurement of body weight, height, triceps skinfold thickness, and mid-arm muscle circumference were performed before and after a 4 month period of out-patient nutritional support. Patients were advised by a dietician on increasing their daily caloric intake by a minimum of 50% above estimated daily energy expenditure. Three patients withdrew from the study. The mean increase in body weight in the nine remaining patients after 4 months of supplementation was 0.3 kg. There was no significant improvement in the anthropometric measures, lung function, respiratory muscle strength or VO2max for the group as a whole. Three patients who gained more than 1 kg weight were from a higher socioeconomic background compared with those who failed to do so. We conclude that achieving weight gain and improving lung function by means of simple out-patient nutritional programmes in a clinical setting is difficult.
Points: Talking points in child abuse
Authors: S. Cordner
Journal: BMJ (1985)

fish rich in o-3 unsaturated fatty acids, including eicosapentaenoic acid (mackerel, herring, salmon, sardines, etc).It would be interesting to know whether Eskimos have a high or low incidence of renal disease, since it is already known that both ischaemic heart disease and many forms of cancer are uncommon in Eskimos eating a high fatty fish diet.7
Chronic hepatitis C
Authors: Kosh Agarwal, Timothy J S Cross, Charles Gore
Journal: BMJ (2007)

Incident reporting should ideally communicate all information relevant to patient safety.Local incident reporting systems in hospitals typically use an incident form that comprises basic clinical details and a brief description of the incident.Such systems are ideally used as part of an overall safety and quality improvement strategy, but in practice they may be dominated by managing claims and complaints. 1 Specialty reporting systems 2 and large scale systems, such as that of the UK National Patient Safety Agency (www.npsa.nhs.uk/),allow wider dissemina-
Beta<sub>2</sub>Microglobulin — Small Molecule — Big Role?
Authors: Edward C. Franklin
Journal: New England Journal of Medicine (1975)

Beta2 microglobulin (β2m) as isolated and characterized from human urine by Berggård and Beam in 1968.1 Though initially of interest largely as an index of renal tubular function, β2m has attracted widespread attention in recent years as a result of the realization that it is an integral component of a number of proteins involved in cell-cell recognition that are coded by a series of closely linked autosomal genes. Since the transplantation antigens are included in this group, β2m is present in the membranes of virtually all cells in every species studied to date.2 3 4 β2m is a protein of molecular . . .
BIOCHEMICAL STUDIES ON SHOCK
Authors: Frank L. Engel, Helen C. Harrison, C. N. H. Long
Journal: The Journal of Experimental Medicine (1944)

1. In a series of rats subjected to hemorrhage and shock a high negative correlation was found between the portal and peripheral venous oxygen saturations and the arterial blood pressure on the one hand, and the blood amino nitrogen levels on the other, and a high positive correlation between the portal and the peripheral oxygen saturations and between each of these and the blood pressure. 2. In five cats subjected to hemorrhage and shock the rise in plasma amino nitrogen and the fall in peripheral and portal venous oxygen saturations were confirmed. Further it was shown that the hepatic vein oxygen saturation falls early in shock while the arterial oxygen saturation showed no alteration except terminally, when it may fall also. 3. Ligation of the hepatic artery in rats did not affect the liver's ability to deaminate amino acids. Hemorrhage in a series of hepatic artery ligated rats did not produce any greater rise in the blood amino nitrogen than a similar hemorrhage in normal rats. The hepatic artery probably cannot compensate to any degree for the decrease in portal blood flow in shock. 4. An operation was devised whereby the viscera and portal circulation of the rat were eliminated and the liver maintained only on its arterial circulation. The ability of such a liver to metabolize amino acids was found to be less than either the normal or the hepatic artery ligated liver and to have very little reserve. 5. On complete occlusion of the circulation to the rat liver this organ was found to resist anoxia up to 45 minutes. With further anoxia irreversible damage to this organ's ability to handle amino acids occurred. 6. It is concluded that the blood amino nitrogen rise during shock results from an increased breakdown of protein in the peripheral tissues, the products of which accumulate either because they do not circulate through the liver at a sufficiently rapid rate or because with continued anoxia intrinsic damage may occur to the hepatic parenchyma so that it cannot dispose of amino acids.
ABC of intensive care: Respiratory support
Authors: M. P Shelly, P. Nightingale
Journal: BMJ (1999)

Most patients admitted to intensive care require some form of respiratory support. This is usually because of hypoxaemia or ventilatory failure, or both. The support offered ranges from oxygen therapy by face mask, through non-invasive techniques such as continuous positive airways pressure, to full ventilatory support with endotracheal intubation.
QUININE IN TONIC WATER
Authors: Stephen Bennett Yohalem
Journal: JAMA (1953)

<h3>To the Editor:—</h3> Cinchonism is relatively rare in the United States both because of the low incidence of malaria and because of the use of the newer antimalarial drugs when indicated. I think it worth while to present to your readers the following unusual reaction because of the increase in popularity, at least in the east, of the drink "gin and tonic." I saw a 43-year-old man in consultation who had a seven week history of tinnitus and hearing loss. He had consulted an otologist, who found bilateral diminution in hearing, and a neurologist, who suggested the diagnosis of bilateral angle meningioma. Because of the history of daily ingestion of seven to eight drinks per day he was sent for a medical evaluation prior to further workup for neurosurgery. The history of alcohol ingestion was correct, but his diet was in general adequate. After a physical examination, which was not
Ga-67 Citrate Accumulation in Adenomatous Goiter
Authors: SHINICHI MIYAMOTO, KANJI KASAGI, RYO TAKEUCHI, AKINARI HIDAKA, HIROTO HATABU, TAKASHI MISAKI, YASUHIRO IIDA, SATSUKI OKANISHI, JUNJI KONISHI
Journal: Clinical Nuclear Medicine (1992)

An elderly woman with a diffusely enlarged goiter and multiple miliary nodular lesions on chest x-ray showed Ga-67 accumulation in the right thyroid lobe. Histologic findings obtained after total thyroidectomy and open lung biopsy revealed papillary carcinoma in the left lobe with pulmonary metastases and adenomatous nodules in the right lobe. This is the first report of Ga-67 accumulation in adenomatous goiter.
P173 Comparison of primary pleural drainage strategies in paediatric empyema
Authors: M. F. Thomas, C. Simmister, D. Cliff, M. A. Elemraid, J. E. Clark, S. P. Rushton, R. Gorton, J. Y. Paton, D. A. Spencer
Journal: Thorax (2011)

<h3>Introduction</h3> Drainage of infected pleural fluid is a key component in the management of paediatric empyema. There is significant controversy regarding management policy resulting in substantial variation in treatment between tertiary centres in the UK. We have compared different primary pleural drainage strategies using a multicentre cohort design. <h3>Methods</h3> Demographic and clinical data on cases of paediatric empyema undergoing pleural drainage were obtained from 19 centres from September 2006 until March 2011. Primary management strategy was defined as that used in the first 48 h of pleural drainage. Robust multivariate survival models were used to analyse length of stay (LOS) and incorporated a frailty term to account for institutional differences. All models were adjusted for age, sex, length of pre-hospital illness, comorbidity and intensive care admission. Fisher9s exact test was used to compare readmission and pneumothorax rates. <h3>Results</h3> Four pleural drainage strategies were recorded in 637 cases (56% male, median age 4.3 years)—Thoracocentesis without fibrinolysis (TC alone, n=35), Thoracocentesis with fibrinolysis (TC-Fib, n=286), Video assisted thoracoscopic surgery (VATS, n=18) and open Thoracotomy (Tho, n=295). Median tertiary LOS was 8 days (range 3–33) and median total hospital stay (THS) 11 days (range 5–43). Results of LOS analysis are shown in Abstract P173 table 1. In comparison to TC-Fib there were no significant differences in either LOS measure for VATS or Tho. TC alone was associated with a 44% increase in LOS at the tertiary centre and a 36% increase in THS, although the THS effect was of borderline statistical significance. There were significant differences in the rates of pneumothoraces between treatment groups (TC alone 11.4%, TC-Fib 4.2%, VATS 0% and Tho 1.69%, p=0.023) but no differences in readmission rates. <h3>Conclusions</h3> Thoracocentesis alone is associated with substantially increased length of hospital stay and increased risk of pneumothorax. There were no significant differences in length of stay or readmission rates between drainage with fibrinolysis, VATS and thoracotomy. Both thoracotomy and VATS were associated with lower risk of pneumothorax but given the overall small number of pneumothoraces this finding should be interpreted with caution.
Janus kinase 2 regulates Bcr–Abl signaling in chronic myeloid leukemia
Authors: A Samanta, B Perazzona, S Chakraborty, X Sun, H Modi, R Bhatia, W Priebe, R Arlinghaus
Journal: Leukemia (2010)

Despite the success of imatinib mesylate (IM) in the early chronic phase of chronic myeloid leukemia (CML), patients are resistant to IM and other kinase inhibitors in the later stages of CML. Our findings indicate that inhibition of Janus kinase 2 (Jak2) in Bcr-Abl+ cells overcomes IM resistance although the precise mechanism of Jak2 action is unknown. Knocking down Jak2 in Bcr-Abl+ cells reduced levels of the Bcr-Abl protein and also the phosphorylation of Tyr177 of Bcr-Abl, and Jak2 overexpression rescued these knockdown effects. Treatment of Bcr-Abl+ cells with Jak2 inhibitors for 4-6 h but not with IM also reduced Bcr-Abl protein and pTyr177 levels. In vitro kinase experiments performed with recombinant Jak2 showed that Jak2 readily phosphorylated Tyr177 of Bcr-Abl (a Jak2 consensus site, YvnV) whereas c-Abl did not. Importantly, Jak2 inhibition decreased pTyr177 Bcr-Abl in immune complexes but did not reduce levels of Bcr-Abl, suggesting that the reduction of Bcr-Abl by Jak2 inhibition is a separate event from phosphorylation of Tyr177. Jak2 inhibition by chemical inhibitors (TG101209/WP1193) and Jak2 knockdown diminished the activation of Ras, PI-3 kinase pathways and reduced levels of pTyrSTAT5. These findings suggest that Bcr-Abl stability and oncogenic signaling in CML cells are under the control of Jak2.
Expression of the rat liver Na+/taurocholate cotransporter is regulatedin vivo by retention of biliary constituents but not their depletion
Authors: C Gartung, S Schuele, S F Schlosser, J L Boyer
Journal: Hepatology (1997)

ABSTRACT Expression and function of the hepatic Na+/taurocholate cotransporter ( ntcp ) are down–regulated in several models of experimental cholestasis. To test whether retention and/or depletion of biliary constituents are involved in ntcp regulation, ntcp expression was quantified in several animal models with altered levels of these constituents. In choledochocaval fistula rats (CCF) (retention model), ntcp mRNA expression specifically declined after 1 and 3 days by 76 ± 4% ( P &lt; .005) and 31 ± 9% ( P &lt; .05), respectively, returning to control levels by 7 days. However, protein expression as assessed by Western blotting remained unchanged for up to 7 days of CCF. In rats with bile fistulas (depletion model) for 0.5, 1, 2, 4, and 7 days, both ntcp protein and mRNA expression remained unaltered. Infusion of either taurocholate or taurochenodeoxycholate for 12 hours also did not effect ntcp mRNA expression in intact animals, probably because of its inability to increase serum and intrahepatic bile acid levels. In rats with selective bile duct ligation (SBDL), ntcp mRNA levels were down–regulated by 40 ± 10% ( P &lt; .05) only after 12 and 24 hours in ligated lobes, and mRNA levels returned to control values in these lobes after 2 and 4 days. ntcp mRNA expression remained unchanged in the nonobstructed lobes at any time. When data from CCF and SBDL rats were combined, serum bile acids correlated linearly with ntcp mRNA (r = .62, P &lt; .0005) over a 0 to 110–micromol/L range. Our results indicate that ntcp is constitutively expressed and remains uneffected by either depletion or increased flux of biliary constituents. However, retention of biliary constituents results in rapid down–regulation of ntcp mRNA, consistent with the concept that hepatocytes may be protected from bile acid toxicity during cholestasis by this mechanism.
Aldosterone, Potassium and Acidosis
Authors: Gordon H. Williams
Journal: New England Journal of Medicine (1976)

In 1957 in the pages of the Journal, Hudson and his colleagues reported the case of a patient with Stokes-Adams attacks and hyperkalemia who also had inappropriately low levels of aldosterone in the urine.1 Since that time at least 30 additional cases of isolated hypoaldosteronism have been reported, including one in the present issue of the Journal (p. 361). The clinical features of this syndrome have varied considerably but except in one case have included hyperkalemia, usually symptomatic, and normal glucocorticoid function, most often established by a normal cortisol or 17-hydroxysteroid response to ACTH administration. In part because of . . .
Subacute Bacterial Endocarditis Due to H. Para-influenzae and Str. Viridans
Authors: J. G. Goudie, C. P. Lowther
Journal: BMJ (1951)

Streptococcus viridans is the infecting organism in most cases of subacute bacterial endocarditis; haemophilic bacteria occur among the rare causal organisms, and of these Haemophilus para-influenzae (Rivers, 1922) is probably the most common (see Miles and Gray, 1938; Craven, Poston, and Orgain, 1940).A case due to this organism was first reported in Britain by Russell -and Fildes (1928).Recently this condition has been recog- nized on a number of occasions and treated beneficially with sulphadiazine (Hunter and Duane, 1946), penicillin and sulphamerazine (Priest et al., 1947), and streptomycin (Briggs and Flinn, 1947;Paul, Bland, and White, 1947;Massel et al., 1948;Olinger, 1948).Endocarditis due to mixed infection with various organisms has also been described; two cases due to
Effect of auranofin on cytokine induced secretion of granule proteins from adherent human neutrophils in vitro.
Authors: J Richter
Journal: Annals of the Rheumatic Diseases (1991)

The effect of auranofin on granule protein secretion from neutrophils was investigated by a haemolytic plaque assay which can detect release of lactoferrin and myeloperoxidase from single adherent neutrophils. Lactoferrin secretion in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) was enhanced at low (0.25-1.0 micrograms/ml) and inhibited at high concentrations of auranofin (50% inhibition (IC50) at 3.7 micrograms/ml). A similar biphasic effect was also seen on degranulation mediated by granulocyte-macrophage colony stimulating factor (GM-CSF) (IC50 1.8 micrograms/ml). In contrast, exocytosis mediated by tumour necrosis factor was inhibited even at low concentrations of auranofin (IC50 0.6 micrograms/ml). Secretion induced by phorbol 12-myristate 13-acetate and A23187 was only inhibited at very high auranofin concentrations (IC50 10 and 8 micrograms/ml respectively). The effect of auranofin on myeloperoxidase secretion was also assessed and the IC50 values for the respective agents were as follows: tumour necrosis factor 0.7 micrograms/ml, fMLP 1.6 micrograms/ml, and phorbol myristate acetate 7.6 micrograms/ml. When neutrophils were preincubated with auranofin (4 micrograms/ml) and then exposed to fMLP, tumour necrosis factor, or GM-CSF in the absence of auranofin, lactoferrin release was enhanced if the preincubation time was short (one to three minutes) and inhibited when the time of preincubation was longer. It was concluded that auranofin, at concentrations achieved in the serum of patients, is a potent inhibitor of cytokine induced release of granule proteins from adherent neutrophils. This finding may be of clinical importance and shed light on the mechanism by which auranofin acts in rheumatoid arthritis.