tbuckley/cabot-search huggingface dataset:
S127 Anti-protein serological responses to Streptococcus Pneumoniae, in diverse populations
Authors: R. J. Wilson, J. M. Cohen, C. Hyams, W. J. van Wamel, C. de Vogel, A. van Belkum, S. B. Gordon, J. S. Brown
Journal: Thorax (2011)

Although vaccine-induced immunity to <i>Streptococcus pneumoniae</i> depends on anti-capsule antibody responses, naturally acquired adaptive immunity may also depend on antibody against surface protein antigens. Unlike capsular antigen, protein antigens are often highly conserved between <i>S pneumoniae</i> strains and thus could be effective vaccines against all <i>S pneumoniae</i> capsular serotypes. We have investigated the pattern of naturally acquired antibodies to <i>S pneumoniae</i> protein antigens in diverse populations and assessed whether they could be protective. Immunoblots against lysates of wild-type and mutant <i>S pneumoniae</i> with sera from adult humans demonstrated antibody responses to a large number of protein antigens including PspC, PspA and PhtD. Using a multiplex assay of 18 recombinant pneumococcal antigens conjugated to fluorescent beads (xMAP) we made semi-quantitative assessments of serological responses in sera obtained from individuals from the UK and Malawi, as well as in commercial immunoglobulin (IVIG) preparations, pooled from donors in either Europe or USA. All individuals, in both geographical populations had significant levels of antibody to a number of pneumococcal proteins. Individuals varied in their response to specific pneumococcal antigens, with absent responses to some antigens that were dominant in other subjects. However, pooled sera from Malawi and IVIG products from both Europe and the USA had remarkably similar patterns of antigen dominance, with consistently high levels of antibody responses to the antigens PhtD, PspC, PspA and PsaA and weak responses to PilusA, Eno, NanA and SlrA. To investigate the functional importance of these protein antigens we used in vitro flow cytometry assays of complement deposition and neutrophil phagocytosis using bacteria which had been incubated in serum pre-treated with the enzyme IdeS (Immunoglobulin-G degrading enzyme of <i>S. pyogenes</i>, which selectively cleaves IgG). Complement deposition and neutrophil phagocytosis of unencapsulated <i>S pneumoniae</i> TIGR4 strain was reduced in IdeS treated serum compared to untreated serum. These data demonstrate that there are naturally acquired functionally significant antibody responses to a range of conserved <i>S pneumoniae</i> protein antigens. The same antigens induce responses in diverse populations, suggesting that these protein antigens would be useful components for a polyvalent protein vaccine that is broadly protective against <i>S pneumoniae</i> infections.
Focal Liver Uptake of Tc-99m Mebrofenin in a Patient With Cavernous Hemangioma
Authors: NACHAR OUSSAMA, VERREAULT JEAN
Journal: Clinical Nuclear Medicine (1998)

A 72-year-old woman had a history of intermittent right upper quadrant pain. A hepatobiliary scan was performed and showed no sign of cholecystitis or other biliary tree abnormality. Focal uptake in the postromedial region (seventh segment) of the liver showed increased intensity with time, whereas the rest of the liver cleared normally (delayed differential washout). This pattern of uptake and washout previously has been observed with adenomas and well-differentiated hepatomas, as well as with some cases of focal nodular hyperplasia. MRI showed the characteristic pattern of hemangioma. Subsequently, a red blood cell scan confirmed the diagnosis of cavernous hemangioma. Hemangioma should be added to the list in the differential diagnosis of focal increased uptake in hepatobiliary scans (1,2). Mechanical compression of the surrounding hepatic parenchyma by the hemangioma resulted in partial obstruction of bile canaliculi, which was attributed to delayed washout.
Incidence of hormone-receptor negative and basal type breast tumors among HLA-A2+patients and possible implications for cancer vaccine trials: U.S. Military Cancer Institute clinical trials group study I-01, I-02, I-03, and I-04.
Authors: JP Holmes, LC Benavides, JD Gates, EA Mittendorf, S Ponniah, GE Peoples
Journal: Cancer Research (2009)

Abstract Abstract #3153 Background: Breast cancer prognosis is significantly impacted by expression levels of steroid hormone receptors for estrogen (ER) and progesterone (PR), as well as HER2/neu, a member of the epidermal growth factor receptor family of tyrosine kinases. Recent advances in molecular typing of breast tumors have defined a poor risk subtype of tumor called basal cell. These basal cell breast tumors are “triple negative,” meaning ER and PR negative, and none to low HER2/neu expression (immunohistochemistry [IHC] 0, 1+, or 2+ tumors). Basal cell tumors have a poorer prognosis and do not respond to conventional hormonal or targeted therapy aimed at HER2/neu overexpressing tumors (IHC 3+). Our Cancer Vaccine Development Program (CVDP) has performed several phase I and II clinical trials using immunogenic peptides from the HER2 protein to include E75, GP2, and AE37. Here we present data analysis of ER, PR, and basal cell tumors in HLA-A2+ and A2- patients. Methods: Vaccine trials utilizing E75, GP2, and AE37 were performed separately with similar designs targeting patients with all levels of HER2 expression (IHC 1-3+). Upon completion of standard breast cancer therapy and prior to HLA-typing, disease-free patients were enrolled in the various vaccine trials. HLA-A2 status was determined via flow cytometry of peripheral blood mononuclear cells as E75 and GP2 are HLA-A2+ restricted whereas AE37 is a promiscuous HLA Class II binder. Standard demographic data (including ER, PR and HER2/neu status) were collected, and patients vaccinated according to their respective trial protocol. Data from all trials were pooled for this analysis. Results: To date, of 254 patients enrolled in the trials 54.3% (n=138) were HLA-A2+. Age, tumor size and nodal status were similar between the A2+ and A2- patients. Significantly more A2+ patients had hormone receptor negative (ER-PR-) tumors (n=49) compared to A2- patients (n=27) (35.5% vs. 23.3%; p= 0.03). There was a trend towards increased basal cell tumors among A2+ patients compared to A2- (15.2% vs. 9.5%; p=0.17). Conclusions: Across these clinical trials conducted by the CVDP, HLA-A2+ patients have an increased incidence of ER-PR- tumors and trend toward increased basal cell tumors. ER-PR- and basal cell tumors have a worse prognosis and fewer treatment options than ER+PR+ tumors. As previously reorted, peptide vaccines targeting the HER2/neu protein are safe and effective in eliciting an immune response in patients with tumors expressing various levels of HER2/neu,to include the low levels associated with basal cell tumors. Therefore, peptide cancer vaccines may provide an excellent adjunctive to current treatment for basal cell tumors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3153.
S94 Stereotactic Radiotherapy for Stage 1 Non Small Cell Lung Cancer: How much occult nodal disease are we missing?
Authors: JM Robson, S Vaidyanathan, MEJ Callister
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Stereotactic Ablative Body Radiotherapy (SABR) has been developed over the last two decades as a method of treating peripheral early stage (T1, T2) NSCLC. It is considered as a valid option for treatment when surgery is high risk or declined. Many clinicians now question whether SABR can be considered as a genuine alternative to surgery for peripheral stage I NSCLC. One concern about any comparison with surgery is that those patients who receive SABR may miss out on adjuvant chemotherapy due to lack of pathological nodal staging that would be done post operatively. Our aim was to determine what proportion of cases this might represent. <h3>Methods</h3> We carried out a retrospective review of surgical resections for lung cancer between 2008 and 2011 at a teaching hospital in Yorkshire. We identified those patients who were staged preoperatively as T1 or T2 with no nodal or distant metastases. We also identified a subgroup of patients with peripheral tumours no greater than 5cm in diameter (i.e. those potentially suitable for SABR). We recorded post operative staging and whether they received adjuvant chemotherapy. <h3>Results</h3> We identified 162 cases in total (81 female) of which 13.7% had nodal involvement on post operative staging. Of these, 72.7% received adjuvant chemotherapy. Within the subgroup with peripheral tumours &lt;5cm there were 116 cases of which 7.0% had nodal involvement. Of these, 62.5% received adjuvant chemotherapy. <h3>Conclusions</h3> Our findings show that a significant number of patients who are preoperatively staged as N0 do have hilar and/or mediastinal nodal involvement at the time of surgery. However, many of these patients have central tumours not suitable for SABR. In the subgroup of patients with small peripheral tumours, that would potentially be suitable for SABR, this proportion is smaller. It is thought that on direct comparison with surgery those who receive SABR might be more likely to develop recurrent disease due to nodal involvement outside of the radiotherapy field in some patients. Our results suggest that this proportion is small. Any effect on overall survival would be weighed against peri-operative morbidity and mortality.
Tc-99m MIBG Imaging in a Huge Clinically Silent Pheochromocytoma with Cystic Degeneration and Massive Hemorrhage
Authors: KAZUYOSHI SUGA, KAZUMI MOTOYAMA, AKIKO HARA, NORIHIKO KUME, MISAKO ARIGA, NAOFUMI MATSUNAGA
Journal: Clinical Nuclear Medicine (2000)

I-131 metaiodobenzylguanidine scintigraphy showed marked accumulation in the walls of a clinically silent, huge cystic adrenal mass with a prominent hemorrhage in a 48-year-old man. Although a careful reexamination of the histologic specimen finally lead to a diagnosis of pheochromocytoma, the appearances of this mass on computed tomography and magnetic resonance imaging were not specific for this neoplasm, and even pathologic analysis initially indicated, incorrectly, that this lesion was a hemorrhagic hemangioma. This case shows that I-131 metaiodobenzylguanidine scintigraphy is useful for correctly diagnosing an adrenal mass with prominent cystic or hemorrhagic degeneration.
AB1045 Effect of strontium ranelate on vertebral pain syndrome and functional abilities in women with glucocorticoid induced osteoporosis
Authors: V. Povoroznyuk, N.I. Dzerovych, L.I. Bondarenco, V.F. Verych, R.E. Gnylorybov, H.M. Hrytsenko, S.B. Kosterin, O.A. Kuhtei, D.G. Recalov, O.V. Synenkii, S.J. Trubina, I.V. Chizwikova, N.I. Shpilevaya, L.G. Jashina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Aim</h3> To evaluate the effect of strontium ranelate in treatment of women with glucocorticoidinduced osteoporosis. <h3>Methods</h3> There were examined 241 women with glucocorticoidinduced osteoporosis (average age 59,6±11,1 years, average height 161,3±6,4 cm, average weight 70,4±12,8 kg). Evaluation of pain syndrome and level of physical activity was carried out with visual analogue scale (VAS). Examination was performed before onset of treatment and after a four, eight and twelve month treatment course. Strontium ranelate (Bivalos, “Servier”) was taken in a dose of one 2 g sachet as a suspension in water once a day and 1 tablet of Calcemin-advance (Calcium – 500 mg, Vit. D – 400 IU) 2 times a day during 12 months. <h3>Results</h3> The patients had the risk factors of osteoporosis: 24% of patients had osteoporotic fractures in their anamnesis; 19% – hip fractures in mother or father of patients and 28% – smoking. We observed a reliable decrease of vertebral pain syndrome after four months of treatment by 14%, after eight months – 35%; after twelve months – 47% (d&lt;0.00001) and increase of functional abilities of patients after four months of treatment by 47%, after eight months – 86%; after twelve months – 100% (d&lt;0.00001). <h3>Conclusions</h3> It has been demonstrated that strontium ranelate treatment significantly decreases pronounced vertebral pain syndrome and improves functional abilities of women with glucocorticoidinduced osteoporosis. <h3>Disclosure of Interest</h3> None Declared.
P18.07 * PALLIATIVE SEDATION FOR BRAIN TUMOR PATIENTS AT THE END OF LIFE
Authors: A. Pace, V. Villani, D. Benincasa, A. Di Pasquale, C. M. Carapella, A. Pompili
Journal: Neuro-Oncology (2014)

BACKGROUND: Therapeutic (or palliative) sedation in the context of palliative medicine is the monitored use of medications intended to induce a state of decreased or absent awareness (unconsciousness) in order to relieve the burden of otherwise intractable suffering in a manner that is ethically acceptable to the patient, family and health-care providers. There is a large debate about the use of palliative sedation, sometime defined as terminal sedation. There are very few data about the role of palliative sedation in brain tumor patients at the end of life. However, in brain tumor patients palliative sedation may be necessary in case of uncontrolled delirium, agitation, death rattle or refractory seizures. METHODS: We retrospectively analyzed the clinical records of patients assisted at home until death by the Regina Elena Cancer Institute Palliative Home Care for brain tumor patients. All patients died for brain tumor in the last 2 years (2012-2013) were included in this study. RESULTS: Out of 190 brain tumor patients assisted at home in 2012-2013, 108 died and were included in this study. All patients were affected by malignant glioma. Palliative sedation was utilized in 12 cases (11%). In 8 cases for the control of refractory seizures and in 4 cases for delirium. Given the lack of advanced directives and low competence of patients, the decision about sedation was discussed by the care team with caregivers and family members. Palliative sedation was started with midazolam 0.5-1 mg/hr and prolonged until symptoms' control. CONCLUSION: The use of palliative sedation is relatively frequent in the practice of a neuro-oncologic palliative team. The most frequent refractory symptoms in this population of patients were seizures and delirium. The process of end of life treatment decisions in neuro-oncology requires to be better defined.
Calcium Supplementation and Increases in Bone Mineral Density in Children
Authors: C. Conrad Johnston, Judy Z. Miller, Charles W. Slemenda, Teresa K. Reister, Siu Hui, Joe C. Christian, Munro Peacock
Journal: New England Journal of Medicine (1992)

Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain.We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years).The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit.In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.
What about the increasing adaptive value of manipulative language use?
Authors: David Kemmerer
Journal: Behavioral and Brain Sciences (1996)

Dunbar (1993) emphasizes the role of cooperative language use in the evolution of human linguistic capacity and neglects to consider the role that manipulative language use would have played. I argue that as group size and neocortieal size increased during human evolution, the adaptive value of using language to benefit oneself at the expense of others would also have increased. I discuss how selection pressures for manipulative language use would have operated in the contexts of mating, status striving, and social exchange.
P1-01-13: Prognostic Impact of CD8 in Node-Negative Breast Cancer.
Authors: M Schmidt, Z Chen, B Hellwig, D Böhm, A Lebrecht, S Gebhard, M Gehrmann, H Koelbl, JG Hengstler
Journal: Cancer Research (2011)

Abstract Background: Infiltration of cytotoxic T lymphocytes (CTL) is a common feature in breast cancer. We examined the prognostic impact of CD8 positive CTL in formalin-fixed-paraffin-embedded (FFPE) tissue using immunohistochemistry (IHC) in node-negative breast cancer and validated our findings in previously published cohorts using RNA expression. Methods: CD8 was evaluated in FFPE tissue of 339 medically untreated node-negative breast cancer patients utilizing IHC. Results were validated utilizing microarray based gene-expression data of four cohorts of medically untreated node-negative breast cancer patients (n=824). Impact of CD8 on metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression. Meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance was examined in the whole cohort and in different molecular subtypes (ER+/HER2−, ER−/HER2−, HER2). Correlation between RNA expression and IHC was analyzed according to Spearman. Results: Immunohistochemical detection of CD8+ CTL was associated with MFS in univariate (hazard ratio [HR] 0.76, 95% confidence interval [95% CI] 0.59−0.98, P=0.037) as well as in multivatiate analysis (HR 0.61, 95% CI 0.46−0.81, P=0.001). Protein levels of CD8 had a good correlation with RNA expression (r=0.488). Higher RNA expression of CD8 was related to better MFS in a meta-analysis of the whole cohort (HR 0.74, 95% CI 0.60−0.90, P=0.0023). However, prognostic significance was confined to ER+/HER2− (HR 0.71, 95% CI 0.51−0.99, P=0.0201) and HER2+ (HR 0.60, 95% CI 0.38−0.97, P=0.037) but not to ER−/HER2− molecular subtypes (HR 0.77, 95% CI 0.52−1.14, P=0.1965). Conclusion: CD8 positive CTL have independent prognostic significance in node-negative breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-13.
Mixed cavernous hemangioma-lymphangioma of the jejunum: detection by wireless capsule endoscopy
Authors: G. Mavrogenis, D. Coumaros, N. Lakhrib, C. Renard, J. Bellocq, J. Leroy
Journal: Endoscopy (2011)

A 26-year-old woman (case 1) was referred for evaluation of recurrent episodes of melena. Gastroscopy, colonoscopy with ileoscopy, and small-bowel computed tomography (CT) scan were normal. Capsule endoscopy (Pill cam SB 2, Given Imaging, Yoqneam, Israel) disclosed a lesion with whitish carpet-like villi and superficial red spots with spontaneous bleeding at the proximal jejunum. At double-balloon enteroscopy (Fujinon, Saitama, Japan) the lesion occupied two-thirds of the lumen ([Fig. 1]).
FRI0357 Assessment of patients with takayasu’s arteritis in a routine clinical follow-up with indian takayasu clinical activity score (itas2010)
Authors: F. Alibaz-Oner, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> ITAS2010 (Indian Takayasu Clinical Activity Score) is a new composite index developed to assess clinical activity in Takayasu's arteritis (TAK), which is weighted for vascular items. In this study, we aimed to investigate the effectiveness of ITAS2010 in the routine clinical follow-up of patients with TAK. <h3>Methods</h3> Patients (n=33, mean age:40.9±12,4 years, F/M:30/3) classified according to ACR criteria for TAK were enrolled. ITAS2010 forms were filled cross-sectionally for baseline for all clinical features and 2 follow-up visits prospectively, with intervals of at least 4-6 months, by including only new or worsening symptoms within the past 3 months. <h3>Results</h3> ITAS2010 was similar at baseline for both active and inactive patients [12 (5-20) vs 10 (0-19), respectively]. There was no correlation between ITAS2010 and acute phase reactants (APRs) in this visit. Similarly, change according to PGA was not reflected in ITAS in the second visit [1,15 (0-6) vs 1,4 (0-3), respectively]. Only in the third visit ITAS2010 score was observed to be significantly higher in active [1,62 (0-7)] patients compared to inactives [0,45 (0-3)](p=0,001). The total agreement between ITAS2010 and PGA was 60% (kappa: 0,096, p=0,43) and between ITAS2010 and <i>Kerr et al</i>. was 74% (kappa: 0,18, p=0,035). The total agreement between PGA and <i>Kerr et al</i>. was 71% (kappa: 0,26, p=0,005). Twelve patients were evaluated with imaging in the follow-up period (4 with PET, 8 with MR-Angiography). When we added an extra score on ITAS2010 for high APRs or positive imaging (vascular progression with radiology or increased uptake on major vascular structures with PET), the total agreement between ITAS2010 and PGA increased to 74% (kappa: 0,499, p&lt;0,001), whereas ITAS2010 and <i>Kerr et al</i>. decreased to 51% (kappa: 0,102, p=0,06). <h3>Conclusions</h3> The agreement between PGA and ITAS2010 was observed to be limited in our study. However, when we combined ITAS2010 with APR or imaging, our results improved. ITAS2010 had a significant discriminatory value according to disease activity in only the third visit in our routine follow-up. These results suggest that ITAS2010 may be valuable in the long-term follow-up of patients with TAK, especially if combined with biomarkers and imaging. <b>Disclosure of Interest</b>: None Declared