tbuckley/cabot-search huggingface dataset:
Magnetic resonance imaging and ultrasonography in predicting pathologic extent after preoperative chemotherapy in stage II-III breast cancer.
Authors: V Guarneri, A Pecchi, P Torricelli, F Piacentini, A Frassoldati, C Mauri, R Battista, B Canossi, R D'Amico, P Conte
Journal: Cancer Research (2009)

Abstract Abstract #4024 Introduction and aims: the main advantage of preoperative chemotherapy (PCT) is tumor down-staging, that can allow either mastectomy in large, inoperable primaries, or breast conserving surgery (BCS) for patients initially candidate to mastectomy. Therefore, an accurate measurement of residual disease after PCT is critical in the optimal surgical planning. Aim of this study is to evaluate the accuracy of breast magnetic resonance imaging (MRI) and ultrasonography (USG) in predicting the extent of breast residual disease.&amp;#x2028; Patients and Methods: patients with stage II-III invasive breast tumor receiving PST and imaged with post-treatment MRI, USG or both were included; deltas were calculated as differences between the longest tumor diameter as measured by MRI and USG and the pathologic size of residual breast tumor. Differences between deltas were tested by using T test for paired data.&amp;#x2028; Results: 45 patients treated with PCT in our Institution were eligible. Patients characteristics were as follows: mean age 50 yrs (range 30-70 yrs); stage IIA 31%, IIB 49%, IIIA-B: 20%. Eighty-nine % of the cases had ductal histology, 69% had ER positivity, and 24% had HER2 over-expression. The mean T size at diagnosis was 3.8 cm (range 1.5-8 cm). PCT type was anthracycline-based (24%) or anthracycline-taxane combination (76%). Forty-four patients have been evaluated after PCT by MRI, 41 by USG, 40 patients by both MRI and USG. The mean T size (range) after PCT was 2 cm (0-6.5 cm) and 1.7 cm (0-5 cm) as measured by MRI and USG respectively. The mean interval between breast imaging and surgery was 20 days (range 1-63). Type of surgery was mastectomy in 45% and BCS in 55% of the cases; 6 patients (13%) achieved a pathologic complete response (pCR). The mean pathologic T size was 1.98 cm (range 0-6 cm). The mean of the deltas were 0.04 (SD 1.91) and -0.19 (SD 1.53) for MRI and USG respectively (p=0.22). A complete response by MRI was observed in 9 cases: 3 cases were confirmed as pCRs; 2 cases presented with scattered microscopic residual disease. An USG complete response was observed in 8 cases (4 confirmed pCRs).&amp;#x2028; Conclusion: in this series of patients, MRI and USG do not show significant differences in predicting the breast residual tumor after PCT. The major challenge for breast imaging after PCT is represented by scattered residual disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4024.
2′,3′-Dideoxyinosine (ddI) in Patients with the Acquired Immunodeficiency Syndrome or AIDS-Related Complex
Authors: John S. Lambert, Mindell Seidlin, Richard C. Reichman, Carol S. Plank, Maura Laverty, Gene D. Morse, Catherine Knupp, Colin McLaren, Carla Pettinelli, Fred T. Valentine, Raphael Dolin
Journal: New England Journal of Medicine (1990)

2',3'-Dideoxyinosine (ddI) is a purine analogue that after intracellular metabolic conversion suppresses the replication of the human immunodeficiency virus (HIV). We conducted a Phase I dose-escalation study of ddI in 17 patients with the acquired immunodeficiency syndrome (AIDS) and 20 patients with AIDS-related complex. The drug was administered twice daily over a dose range of 0.4 to 66 mg per kilogram of body weight per day for 2 to 44 weeks. The maximal tolerated oral dose of ddI was estimated to be 12 mg per kilogram per day. The major dose-limiting toxic effects were a painful peripheral neuropathy (in eight patients) and pancreatitis (in five). Asymptomatic elevations of the serum aminotransferase levels (in 13 patients) and the serum urate level (in 10) were also noted, but there was no dose-related hematologic toxicity. At the maximal tolerated dose, the peak plasma levels of ddI were 6.3 to 9.6 mumol per liter 0.6 to 1 hour after oral administration; the mean plasma half-life was 1.5 hours. The administration of ddI was associated with statistically significant decreases in serum level of p24 antigen and increases in the numbers of CD4 cells at 2, 6, 10, and 20 weeks. These changes were seen at all dose levels studied. Either a clinical improvement or a weight gain of greater than or equal to 2 kg was observed in 25 of 34 patients at six weeks. We conclude that ddI is a promising therapeutic agent in patients with AIDS or AIDS-related complex. Its efficacy is currently being evaluated in large-scale, controlled clinical trials.
Uruguay's mandatory breast cancer screening for working women aged 40-59 is challenged
Authors: S. Arie
Journal: BMJ (2013)

A woman in Uruguay is challenging the obligation for working women aged between 40 and 59 years to be screened for breast cancer every two years.

A decree issued in 2006 by the then president, Tabare Vazquez, an oncologist, made biennial screening for breast cancer a part of a series of regular, state funded health checks that female employees must complete to get the “health card” that all workers need.

A 52 year old state sector computer engineer is the first person known to have refused screening. She recently began legal proceedings to seek …
Abstract 1176: Bypassing the dominant-negative effect of mutant p53 in cancer cells
Authors: Abood Okal, Mohanad Mossalam, Karina J. Matissek, Carol S. Lim
Journal: Cancer Research (2012)

Abstract The tumor suppressor p53 is mutated in more than 50% of all cancers. The transcriptional activity of p53 depends on localization to the nucleus and formation of p53 tetramers. Use of wild-type (wt) p53 for gene therapy is limited due to the dominant-negative effect of mutant (mut) p53 over wt p53. Mut p53 will hetero-oligomerize with wt p53 via the tetramerization domain (TD) found in p53, deactivating the tumor suppressor function of wt p53. In order to use p53 for gene therapy, an alternative oligomerization domain for p53 was investigated. The coiled-coil (CC) domain from Bcr (breakpoint cluster region), similar to the native TD of p53, can form an antiparallel dimer of dimers. The TD from p53 was then substituted with this CC, and the activity of this new p53 (p53-CC) was tested. We evaluated the transcriptional activity of p53-CC compared to wt p53 in a dual luciferase reporter gene assay. To demonstrate the ability of our p53-CC to bypass the dominant-negative effect prompted by hetero-oligomers, the reporter gene assay was carried in human breast adenocarcinoma (MCF-7) and human breast ductal carcinoma (T47D) cell lines. MCF-7 cells contain wt p53 population that is mislocalized to the cytoplasm, whereas, T47D cells contain mutant p53. Indeed, data from the reporter gene experiment shows a reduction in wt p53 activity introduced to T47D cells compared to MCF-7 cells, while the activity of p53-CC remains consistent regardless of the presence of an endogenous mut p53 population. We also tested the biological activity of p53-CC and its ability to induce apoptosis using 7-AAD and Annexin-V assays (late stage apoptosis). In addition, Caspase-3/7 assay (mid-stage apoptosis) was performed to further validate a p53-dependent apoptotic pathway. Data obtained from the aforementioned experiments suggest that p53-CC has a very similar biological activity to wt p53. Furthermore, we examined the gene expression profile of p53-CC using wt p53 as a reference. The assay was performed using real-time PCR array technology to analyze the expression of 84 genes related to p53-mediated signal transduction. Two negative controls were used; the first is a p53 construct that lacks its tetramerization domain (p53ΔTDC) and should not possess any transcriptional activity, and the second is the CC by itself. Indeed, p53-CC shows comparable gene expression profile to wt p53 and has the ability to transactivate the various p53 target genes. In summary, p53-CC retains p53 activity and excludes hetero-oligomer formation, overcoming a major barrier in using p53 for cancer gene therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1176. doi:1538-7445.AM2012-1176
Basis for Recurring Ventricular Fibrillation in the Absence of Coronary Heart Disease and Its Management
Authors: Bernard Lown, John V. Temte, Peter Reich, Charles Gaughan, Quentin Regestein, Hamid Hai
Journal: New England Journal of Medicine (1976)

A 39-year-old man twice experienced ventricular fibrillation and exhibited numerous ventricular premature beats. Coronary arteries were normal, and no impaired cardiac function was found upon catheterization. Evidence was adduced that the ventricular premature beats were related to higher nervous activity. The patient had serious psychiatric problems; the ventricular premature beats were provoked by psychophysiologic stress, increased during REM sleep, were reduced by meditation, and were controlled by beta-adrenergic blockade, phenytoin and digitalization. We conclude that psychologic and neurophysiologic factors may predispose to life-threatening cardiac arrhythmia in the absence of organic heart disease. Effective management of the recurrent ventricular arrhythmia involved; acute drug testing for assessing antiarrhythmic efficacy; use of programmed trendscription to provide on-line information on drug action; a treatment program involving more than one agent; and use of measures to reduce sympathetic nervous activity.
IMPROVING THE DIAGNOSIS OF ACUTE MYOCARDIAL INFARCTION BY DERIVING EPICARDIAL POTENTIALS FROM THE BODY SURFACE POTENTIAL MAP USING INVERSE ELECTROCARDIOGRAPHY AND AN INDIVIDUALIZED TORSO MODEL
Authors: Michael Daly, Dewar Finlay, Daniel Guldenring, Raymond Bond, Aaron McCann, Peter Scott, Jennifer Adgey, Mark Harbinson
Journal: Journal of the American College of Cardiology (2016)
AB0767 The association of ferritin autoantibodies with takayasu arteritis
Authors: K. Große, F. Moosig, R.E. Schmidt, T. Witte, N.T. Baerlecken
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Takayasu arteritis (TA) may be difficult to diagnose since diagnostic biomarkers have not been established so far. In a previous study, we could show the presence of autoantibodies against the human ferritin heavy chain protein (HFC) in sera of patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) (1). <h3>Objectives</h3> To study the prevalence of autoantibodies against HFC in TA. <h3>Methods</h3> We established 7 ELISAs for the detection of autoantibodies against HFC. As autoantigen we used the full recombinant HFC expressed by E. coli or one of six different peptides of the HFC: 1-18Aa (purity 98.8%), 19-45Aa (purity 98.8%), 52-78Aa purity 98.3%), 79-104Aa (purity 98.8%), 105-143Aa (purity 98.4%), 145-183Aa (purity 98.5%). We collected sera of 51 patients with TA, 49 sera of fever patients with underlying chronic infectious and malignant diseases, which are known for having unspecific autoantibodies, and 100 blood donors' sera served as controls. <h3>Results</h3> The best results were obtained by using ferritin pedtides as antigens. By combining different ELISAs detecting autoantibodies against HFC peptide 19-44A, 79-104A and 105-144A, we were able to detect ferritin peptide antibodies in 31/51 (61%) TA patients. For early TA, the frequency was lower than in early GCA and PMR (previous study up to 92%). In the controls, 0/100 (0%) of the <i>blood donors</i> were positive and 11/49 (22%) of the fever patients were positive. <h3>Conclusions</h3> Considering the lack of biomarkers for TA, autoantibodies against peptides of HFC could be helpful as a marker for TA. <h3>References</h3> Baerlecken NT, Linnemann A, Gross WL, Moosig F, Vazquez-Rodriguez TR, Gonzalez-Gay MA, Martin J, Kötter I, Henes JC, Melchers I, Vaith P, Schmidt RE, Witte T. Association of ferritin autoantibodies with giant cell arteritis/polymyalgia rheumatica. Ann Rheum Dis. 2012 Jan 5. [Epub ahead of print] <h3>Disclosure of Interest</h3> None Declared
SAT0184 Predictors of response to induction therapy in lupus nephritis
Authors: D.G. Miranda-Hernandez, C.V. Cruz-Reyes, U. Angeles, L.J. Jara, M.A. Saavedra
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Several prognostic factors have been described in lupus nephritis, which vary depending on the population studied. Few studies have examined these factors in relation to different stages of treatment. <h3>Objectives</h3> To identify prognostic factors associated with response to induction therapy in LN according to the stages of treatment. <h3>Methods</h3> We performed a retrospective case-control study nested in a cohort of patients with systemic lupus erythematosus (SLE) with biopsy-proven LN according to WHO, in a period from January 2001 to December 2008. All patients received induction therapy remission and had a minimum follow-up period of two years. Patients were divided in 2 groups: group 1, responders (presence of inactive sediment, proteinuria &lt;0.5 g/day, and estable renal function) and group 2: non-responders (active sediment, proteinuria &gt;0.5 g/day, and decrease renal function) at 6, 12, and 24 months. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy including age, gender, duration of SLE, duration of LN, histologic type, delay in treatment, biochemical (serum creatinine, urinary active sediment, creatinine clearance, proteinuria), and immunological parameters (complement C3, C4 and anti-dsDNA antibodies). We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. <h3>Results</h3> We reviewed clinical records of 168 patients, 141 of female (84%), with average age at diagnosis of LN of 30.4±10.6 years, the mean time of evolution of SLE until LN diagnosis was 28.0±48.8 months. LN was initial manifestation of SLE in 94 (56.5%) patients, renal biopsy showed: type II in 33 patients (19.6%), class III in 28 (16.6%), class IV in 92 (54.7%), class V in 7 (10.2%) and a combination in 7 (10.2%). One-hundred and thirteen (67%) patients received pulses of cyclophosphamide as induction therapy, the response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis with lack of therapeutic response as the dependent variable is shown in the following table: <h3>Conclusions</h3> The main predictor of poor therapeutic response at 24 months is the delay in treatment. At 12 months is low creatinine clearance. Patients younger than 25 years and microhematuria are the best responders to treatment at 6 months. Male gender and elevated creatinine and hypocomplementemia were not factors of poor therapeutic response. Early treatment of lupus nephritis is associated with favourable response to two years. <h3>Disclosure of Interest</h3> None Declared
AB0708 Neuropsychiatric manifestations in systemic lupus erythematosus: About 80 tunisian patients
Authors: S. Sayhi, F. Ajili, I. Gharsallah, L. Metoui, S. Kouki, N. Benabdelhafidh, J. Laabidi, B. Louzir, F. Msaddak, N. Ben Abdallah, S. Othmani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a relapsing-remitting autoimmune disease. The frequency of neuropsychiatric manifestations in SLE studies varies widely, depending on the type of manifestations included and the methods used for evaluation. Neuropsychiatric (NP) manifestations may be considered primary if directly related to SLE activity, or secondary when related to treatment, infections, metabolic abnormalities or other systemic manifestations such as uremia and hypertension. <h3>Objectives</h3> To evaluate the prevalence and characteristics of different neurological and psychiatric presentations in patients admitted to the department of Internal Medicine of the Military Hospital of Tunis hospital with systemic lupus erythematosus (SLE). <h3>Methods</h3> In this retrospective hospital-based study, we examined the medical records of 80 patients with SLE from 2000 to 2010 in our department. All patients fulfilled the criteria of the American College of Rheumatology (ACR). <h3>Results</h3> Eighteen (80) SLE patients were included in the study. The prevalence of neuropsychiatric syndromes in our study was estimated to be 27% and the most frequent NP syndromes were headaches (28%), seizures (27%) and cognitive dysfunctions (21%). Meningitis, convulsions and cerebrovascular events were found respectively in: 16 cases (21%), 11 cases (16%) and 6 cases (7%). One patient had an optic neuropathy and onether extrapyramidal syndrome. No cases of plexopathy or Guillain-Barré syndrome were reported. MRI abnormalities were found in 21 cases (27%).Glucocorticoids and immunosuppressive therapy were indicated when NP manifestations were thought to reflect an inflammatory process in SLE(optic neuritis, refractory seizures, psychosis) and in the presence of generalized lupus activity. Antiplatelet and anticoagulation therapy were indicated when manifestations are related to antiphospholipid syndrome. <h3>Conclusions</h3> The prevalence and nature of different neurological presentations of SLE in Tunisian patients has some similarities to that reported in the literature. Differences are due to ethnic and environmental factors <h3>References</h3> Jennekens FG, Kater L. The central nervous system in systemic lupus erythematosus Part 1: Clinical syndromes: A literature investigation. Rheumatology 2002;41:605-18. [PUBMED] [FULLTEXT] Weiner SM, Peter NH. Neuropsychiatric involvement in systemic lupus erythematosus: Part 1: Clinical presentation and pathogenesis. Med Klin (Munich) 2002;97:730-7. Futrell N, Schultz LR, Millikan C. Central nervous system disease in patients with systemic lupus erythematosus. Neurology 1992;42:1649-57. <h3>Disclosure of Interest</h3> None Declared
P07.01 * NEUROSURGICAL TREATMENT OF SPINAL TUMORS IN THE ELDERLY
Authors: D. Brunozzi, M. Dobran, M. Iacoangeli, A. Di Rienzo, N. Nocchi, R. Colasanti, C. Vaira, D. Nasi, F. Forconesi, M. Scerrati
Journal: Neuro-Oncology (2014)

INTRODUCTION: Thanks to the increasing life expectancy and to the improvements made in the treatment of systemic diseases and cancer, combined with advancements in imaging technology, the incidence of spinal tumors has greatly increased in the elderly population. Metastases constitute the majority of lesions, while benign tumors accounts for 25-30% of all spinal neoplasms. The hesitation in performing spinal surgery in aged people is related to the greater likelihood of intra and post-operative complications. Despite this concrete risk, the need for histological diagnosis, root and/or spinal cord decompression, pain relief and improvement of quality of life make surgery quite often a necessary option for this cohort. The primary goal of surgery depends on Histology and tumor extension, but the best surgical result should be faced with the minimal invasiveness, in order to decrease the possible spinal instability and postoperative morbidity and mortality. MATERIALS AND METHODS: We report a series of 70 patients, aged 70 years or more, treated by minimally invasive approach from 2008 to 2013. Forty patients harboured spinal bone metastases, 30 patients benign extramedullary lesions, mainly meningiomas. Surgery was performed to achieve diagnosis and/or decompression of neurological structures; the additional aim for benign lesions was total resection and the further surgical indication for spinal metastases was pain relief. RESULTS: Mono or multisegmental hemilaminectomy in order to preserve the spinal stability was performed in all cases of meningiomas, with gross total removal in 28 patients and subtotal resection in 2 patients. Laminectomy and/or vertebroplasty were performed in the 30% of metastatic cases, followed by internal fixation with screws and rods in the majority of cases in order to reduce back pain primary due to spinal instability. Although this last procedure is not intrinsically minimal invasive, it was performed considering the minimally invasive attitude. Improvement of neurological deficits was achieved in 90% of patients with benign lesions and in the 38 % of spinal metastatic group. In this last group pain relief was also reached in 55% of patients. The rate of mortality, major morbidity and postoperative quality of life was comparable to that of the younger patients. CONCLUSIONS: Until the previous decade, age itself represented quite often a contraindication for surgery, particularly because of the presumed high risk of postoperative morbidity and mortality. Nowadays, planning a tailored anesthetic protocol, surgical strategy and meticulous postoperative assistance, surgical treatment can be offered to this cohort of patients, because their quality of life, referring to neurological deficits and pain, can be greatly improved in the vast majority of cases.
Carbon dioxide enterography: a useful method for double-balloon enteroscopy-assisted ERCP
Authors: Nobuhiko Fukuba, Ichiro Moriyama, Shunji Ishihara, Takafumi Yuki, Kousaku Kawashima, Norihisa Ishimura, Yoshikazu Kinoshita
Journal: Endoscopy (2014)

Development of double-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (DB-ERCP) has enabled endoscopic treatment of pancreatobiliary disease in patients with a surgically altered gastrointestinal anatomy [1]. However, scope insertion requires experience because of the maze-like gastrointestinal tract [2]. Intraluminal injection of indigo carmine to identify the afferent loop of Roux-en-Y anastomosis [3] may cause susceptibility to peristalsis and is unsuitable for complex reconstruction. To develop a smooth insertion method, we used a negative contrast technique with carbon dioxide to confirm the correct tract, termed CO2 enterography, and we present case results here.
Effects of Fructose on Hypoglucosemia in Infants of Diabetic Mothers
Authors: Michael L. McCann, Chiung Hui Chen, Edgardo B. Katigbak, Jane M. Kotchen, Beverly F. Likly, Robert Schwartz
Journal: New England Journal of Medicine (1966)

GESTATIONAL diabetes (termed "pre-diabetes" by some investigators) offers a unique opportunity to investigate the influence of an altered maternal environment on the carbohydrate metabolism of the newborn infant. Previous attention has been called to infants of insulin-dependent mothers.1 2 3 4 The present observations indicate that hypoglucosemia†† is a common phenomenon in infants of mothers with gestational diabetes as well and that it is related to the degree of maternal glucose intolerance. The influence of fructose on the infant's metabolism of glucose was also evaluated.MethodsFrom July, 1963, to August, 1965, 60 normal infants and 56 infants of diabetic mothers from greater . . .