tbuckley/cabot-search huggingface dataset:
Circulating Neuroblastoma Cells Detected by Reverse Transcriptase Polymerase Chain Reaction for Tyrosine Hydroxylase mRNA Are an Independent Poor Prognostic Indicator in Stage 4 Neuroblastoma in Children Over 1 Year
Authors: Susan A. Burchill, Ian J. Lewis, Keith R. Abrams, Richard Riley, John Imeson, Andrew D.J. Pearson, Ross Pinkerton, Peter Selby
Journal: Journal of Clinical Oncology (2001)

In this prospective, multicenter study, the independent prognostic power of neuroblastoma cells detected by reverse transcriptase polymerase chain reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated.The clinical significance of disease detected by RT-PCR in peripheral blood from children at diagnosis was compared with established prognostic markers [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and MYCN gene amplification] by multivariate analysis. The value of disease detection by RT-PCR during treatment and follow-up was also examined.TH mRNA was detected in peripheral blood from 33 of 49 (67%) children with stage 4 neuroblastoma > 1 year old at diagnosis and was a significant predictive factor for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19 to 4.84, P =.014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P =.034) in a multivariate analysis. Detection of disease in blood from clinically disease-free children was related to increased risk of death (HR 2.54, 95% CI 1.42 to 4.55, P =.0014).TH mRNA in peripheral blood of children with neuroblastoma is a poor prognostic indicator, reflecting the propensity for dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L, this is the most powerful poor prognostic model at diagnosis for children > 1 year old with stage 4 disease. The detection of TH mRNA in peripheral blood from clinically disease-free children is related to increased risk of relapse and death.
Appropriate feeding methods for infants of HIV infected mothers in sub-Saharan Africa Commentary: The feeding debate is still unresolved and of secondary importance
Authors: M. C Latham
Journal: BMJ (2000)

# Appropriate feeding methods for infants of HIV infected mothers in sub-Saharan Africa {#article-title-2} HIV and AIDS have seriously affected women of reproductive age in sub-Saharan Africa. In 1998, an estimated 590 000 infants worldwide acquired HIV-1 from their mothers; 90% of these infants were in Africa.1 Transmission of HIV from mother to child mainly occurs in utero and during delivery, but in a few cases it happens through breast feeding.2 Increased attention is being focused on strategies to prevent vertical transmission of HIV.3 These strategies need to be based on risk assessment and on cost effectiveness analysis. Interventions are aimed at preventing transmission in utero and during delivery or during breast feeding. Here we discuss only the appropriate infant feeding practices for HIV-1 infected mothers living in poor households in sub-Saharan Africa. #### Summary points Concern is increasing over mother to child transmission of HIV in sub-Saharan Africa Decisions about interventions must be based on assessment of risks, costs, and benefits The role of breast feeding in the vertical transmission of HIV has been exaggerated Exclusive breast feeding reduces HIV transmission Promoting infant formula feeding to prevent HIV infection might increase infant morbidity, malnutrition, and mortality More research on alternative infant feeding methods is urgently needed In many African countries, the HIV and AIDS pandemic is a major tragedy of unprecedented proportions that is increasingly affecting mothers and their children. However, even responsible health agencies have tended to exaggerate the role of breast feeding in transmission. It is estimated that in countries with a low seroprevalence of HIV (5% of women infected) fewer than 1% of all infants are likely to become infected through breast feeding, whereas in those with a high prevalence (25% of women infected) fewer than 4% of infants will be affected through lengthy breast feeding.4 If preventing a child from acquiring HIV infection through breast milk were the … Correspondence to: K Zwi, 1/10 Oaks Avenue, Cremorne, NSW 2090, Australia
Panitumumab and cetuximab epitope mapping and in vitro activity
Authors: D. Freeman, J. Sun, R. Bass, K. Jung, S. Ogbagabriel, G. Elliott, R. Radinsky
Journal: Journal of Clinical Oncology (2008)

14536 Background: Panitumumab, a fully human monoclonal antibody against epidermal growth factor receptor (EGFR), has anti- tumor activity as monotherapy in both preclinical models and clinical trials. The objective of this study was to identify the epitope on EGFR for panitumumab and compare it to that of cetuximab, a chimeric anti-EGFR Ab. Methods: The extracellular domain of EGFR (amino acids 1–618) and domains I, II, III, IV individually were expressed to determine the domain on EGFR that was necessary for panitumumab binding. Chromatography was used to compare the binding affinity of panitumumab vs cetuximab. By flow cytometry and amino acid replacement scanning, the critical residues involved in panitumumab and cetuximab binding for EGFR were determined. Using diffraction data from the panitumumab Fab'2 and published data for cetuximab, crystal structure models of EGFR and the residues determined to be critical for panitumumab or cetuximab binding were built. To evaluate in vitro activity, A549 NSCLC cells were treated with 20μg/ml of panitumumab or cetuximab for 1 hour prior to a 15-minute stimulation with known EGFR ligands (TGF-α, amphiregulin, epiregulin, HB-EGF, betacellulin, and EGF). Inhibition of ligand-induced phosphorylation of EGFR was determined using a specific anti-pEGFR (pY1068) antibody. Results: Truncation analysis by flow cytometry narrowed the binding epitopes of panitumumab and cetuximab to domain III of EGFR. Point mutations revealed that amino acids 349, 355, 412, and 438 were critical for panitumumab and cetuximab binding. A 2.9 Angstrom crystal structure of the panitumumab Fab'2 was solved. Models of the panitumumab-EGFR and cetuximab-EGFR complexes were generated and predicted that the CDRs for both light and heavy chains would be proximal to domain III of EGFR. From in vitro studies, panitumumab and cetuximab can inhibit receptor activation of all known EGFR ligands in A549 NSCLC tumor cells. Conclusion: Panitumumab and cetuximab bind to comparable surface exposed amino acids in domain III of EGFR and inhibit all known EGFR ligands, resulting in inhibition of receptor activation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen Inc.
Canine Bone Sarcoma: Estimation of Relative Risk as a Function of Body Size
Authors: Tjalma Ra
Journal: JNCI Journal of the National Cancer Institute (1966)

Larger canine breeds are subject to excess relative risk of primary bone sarcoma. Based on comparison of normal population samples and the 404 cases studied, the risk of bone sarcoma among giant dogs (over 80 lbs.) is estimated to be no less than 61 times the risk among small dogs (<20 lbs.), and possibly as high as 185 times the risk for small dogs. A preliminary indication of increased risk of cancer other than bone sarcoma among larger breeds complicates interpretation of bone sarcoma risk values; if the larger breeds are subject to a greater probability of clinical attention for all types of cancer, the actual risk of bone sarcoma among giant dogs may be as low as 29 times the risk among small dogs. Among giant dogs the risk of bone sarcoma is estimated to be no less than 5, and possibly as high as 30, times the risk of cancer other than bone sarcoma. Study results indicate the excess risk of bone sarcoma is characteristic of the larger breeds as a group rather than of one or several particular breeds.
Use of fibreoptic bronchoscopy in early diagnosis of sputum smear-negative pulmonary tuberculosis
Authors: Hoi-Yee Kwan, Susanna Lau, Kah-Lin Choo, Wai-Kei Lam, Chun-Man Wong, Chin-Wing Yu, Tze-Lun Wong, Wing-Yan Chu, Kwan-Keung Wong
Journal: European Respiratory Journal (2011)

Background:  Pulmonary tuberculosis (PTB) is a major health problem worldwide. Rapid diagnosis allows early treatment and infection control, which is hard to achieve among sputum smear-negative (SSN) subjects. Different bronchoscopic sampling techniques have been used but their roles remain unclear.   Objectives:  To evaluate the value of fibreoptic bronchoscopy in the diagnosis of PTB among SSN patients in a regional hospital in Hong Kong.   Methods:  Medical records of 22 patients, who have underwent bronchoscopy in the North District Hospital, HKSAR, in 2009, and were later diagnosed of having PTB, were reviewed. Results of their pulmonary specimens were recorded. The exclusive diagnostic test was identified.   Results:  Bronchoalveolar lavage (BAL) was performed in all 22 cases. Positive acid-fast smear and culture were obtained in three (13.6%) and six cases (27.3%) respectively, providing the exclusive means of diagnosis for four cases (three from smear, one from culture). Molecular study from BAL was done in 14 cases, in which five cases were test positive (35.7%), two cases gave exclusive diagnosis. Transbronchial lung biopsy (TBLB) was performed in 19 cases. All were sent for histology, while six were sent for acid-fast bacilli (AFB) culture. Histology gave positive results in five cases (26.3%), which was the exclusive means of diagnosis for two. TBLB AFB smear was all negative, but three gave positive AFB culture. Among them, one provided exclusive diagnosis.   Conclusion:  While sputum examination remains the cornerstone in diagnosing PTB, fibreoptic bronchoscopy plus various sampling techniques served as a useful adjunct to optimize the diagnostic yield, especially among those SSN cases.
Population study of dihydropyrimidine dehydrogenase in cancer patients.
Authors: M C Etienne, J L Lagrange, O Dassonville, R Fleming, A Thyss, N Renée, M Schneider, F Demard, G Milano
Journal: Journal of Clinical Oncology (1994)

PURPOSE We conducted a prospective study on a large set of cancer patients in an attempt to evaluate the incidence of complete or partial dihydropyrimidine dehydrogenase (DPD) deficiency as found in peripheral mononuclear cells (PMNC). PATIENTS AND METHODS One hundred eighty-five unselected consecutive cancer patients were included. The population consisted of 152 men (mean age, 62.1 years; range, 35 to 90) and 33 women (mean age, 59.2 years; range, 36 to 77). Sixty-eight were head and neck patients treated by a 5-day continuous infusion of fluorouracil (FU; starting dose, 1 g/m2/d, with dose adaptation based on pharmacokinetics) for which DPD activity was measured 2 to 3 days before FU administration (94 cycles analyzed). PMNC-DPD activity was measured by a radio-enzymatic assay using carbon-14-FU. RESULTS DPD activity in the entire population showed a unimodal distribution, which globally fits a gaussian distribution. Mean and median DPD activity values were 0.222 and 0.211 nmol/min/mg protein, respectively (range, 0.065 to 0.559). No total DPD deficiency was found. Multifactor analysis of variance showed that liver function (biologic evaluation) and age did not influence DPD activity, but that DPD activity was, on average, 15% lower in women (0.194 nmol/min/mg protein) than in men (0.228 nmol/min/mg protein) (P = .03). No difference was demonstrated between premenopausal and postmenopausal women. In patients treated with FU, the risk of developing side effects was not linked to pretreatment DPD activity. FU-related toxicity was linked to FU systemic exposure. The correlation between pretreatment DPD activity and FU systemic clearance (CI) was weak (n = 90, linear regression r = .31, P = .002). Pretreatment DPD activity in patients who required a dose reduction was not significantly different from DPD activity in patients who did not require dose modification. CONCLUSION From the present study, it appears that total DPD deficiency is a rare event. Although pretreatment DPD activity cannot be a useful indicator for improving FU dose adaptation strategy, the identification of severe DPD deficiency (&lt; 0.100 nmol/min/mg protein) could lead to starting the treatment with a markedly reduced FU dose or even to using an alternative chemotherapy regimen.
Not all antistatic valved holding chambers have equivalent performance: An example why each valved holding chamber (VHC)-inhaler combination should be considered unique
Authors: Jamie Malpass, Mark Nagel, Valentina Avvakoumova, Rubina Ali, Heather Schneider, Jolyon Mitchell
Journal: European Respiratory Journal (2012)

RATIONALE:  Electrostatic charge mitigation by the use of charge dissipative materials with VHCs is common, since initial pre-washing can be avoided. We compared 9antistatic9 VHCs; Optichamber® Diamond® (OD), Phillips Healthcare with AeroChamber Plus® Flow-Vu® (AC Flow-Vu) Trudell Medical International) (n=4 devices/group), to determine suitability for patients delaying inhalation post-actuation.   METHODS:  An abbreviated Andersen impactor that determined fine particle mass   ) was used with an apparatus simulating 2, 5 and 10 s delay intervals following pMDI actuation (Flovent®, GSK plc, 125 µg/actuation fluticasone propionate (FP)). This approach conforms to guidance from European authorities that testing of VHCs should simulate delayed inhalation. Assay for FP was undertaken by HPLC-UV spectrophotometry. Measurements without delay were undertaken to assess mass recovery for FP, validating the procedure. All values are mean±SD.   RESULTS:  Mass recoveries (131.5±2.9 and 130.7±3.8 µg/actuation for the OD and ACPlus VHCs respectively) were close to label claim, validating system suitability. The variation of FPM   with delay interval is shown in the Table.  The ratio FPM  /FPM  ) increased from 1.2 (2-s) to 1.4 (5-s) and to 1.6 (10-s), demonstrating faster depletion of the therapeutically beneficial medication from the OD.   CONCLUSION:  Not all VHCs manufactured from anti-static materials provide optimum performance for patients who have poor coordination.
Short-term Analysis vs Long-term Data on Total Hip Replacement Survivorship
Authors: Constance R. Chu
Journal: JAMA Surgery (2015)

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Measuring the detriment of treatment: number needed to harm
Authors: P. Sedgwick
Journal: BMJ (2015)

Researchers investigated the efficacy and safety of nicotine patches in pregnant women who smoked. A randomised placebo controlled trial was performed. The intervention consisted of the administration of 16 hour nicotine patches until the time of delivery. Participants were pregnant women over 18 years who smoked at least five cigarettes a day and whose babies were between 12 and 20 weeks’ gestation. In total, 402 women were recruited from 23 maternity wards throughout France and randomly allocated to the intervention (n=203) or placebo patches (n=199).1 The primary outcome measures were achievement of complete abstinence until delivery and birth weight. The proportion of women who achieved complete abstinence was higher in the nicotine patch group than in the placebo group, although the difference was not significant (5.5% (n=11) v 5.1% (n=10); P=0.87). The mean birth weight was higher in the nicotine patch group, although the difference was not significant (3065 (standard error 44 g) v 3015 g (44 g); P=0.41). The incidence of serious adverse events (including stillbirth, late miscarriage, and newborn death at birth) was similar between the treatment groups. Non-serious adverse reactions, mainly affecting the skin, were more common in the nicotine patch group than in the placebo patch group. In particular, skin reactions at the patch site were reported by 23 (11.33%) women in the intervention group compared with 8 (4.02%) in the placebo patch group (number need to harm 13.7; 95% confidence interval 8.0 to 46.1). It was concluded that the nicotine patch did not increase the smoking cessation rate or birth weight, although it increased the frequency of non-serious adverse reactions, mainly those affecting the skin. Which of the following statements, if any, are true?
Uncomplicated dementia in very elderly patients can be a cause of NIV treatment failure
Authors: Giuseppe Emanuele La Piana, Simona Scorsetti, Stefano Aiolfi
Journal: European Respiratory Journal (2013)

Introduction : Initial trials on Noninvasive ventilation (NIV) have proven to be effective also in elderly patients with hypercapnic respiratory failure because it reduces respiratory distress without the need of endotracheal intubation, and improves survival. Compliance to ventilation is considered the most important cause of NIV treatment failure and in this population the presence of dementia as comorbidity could be responsible of an extra-deterioration in the patient’s ability in affording NIV.

Aim : To evaluate the dementia as a cause of an increased NIV treatment failure because of a lower compliance to ventilation in these patients.

Results : 22 pts aged ³ 80 years (84,2±3,5) (Group A) and 8 pts with diagnosis of uncomplicated dementia, base don DSM-IV criteria, aged ³ 80 years (83±1,2) (Group B) with cardiogenic pulmonary edema or acute-on-chronic respiratory failure from COPD underwent NIV. On admission the two groups showed no differences (p>0.05) in PaO2 mm Hg (53±8 vs 52±8), PaCO2 mmHg (62±12 vs 66±14), pH (7,30±0,1 vs 7,29±0,1), and in SAPS II score.

After 48 h of ventilation there was a difference in pH levels (7.36±0,1 vs 7,26±0,1; p = 0,048) between the two groups. From the assessment of clinical charts it emerged that patients of Group B were more intolerant to NIV and frequently disconnected from ventilation. The mean use of NIV in the first 48 h was: Group A 35 h; Group B 16 h. Mortality was 6/22 (27%) in Group A and 6/8 (75%) in Group B.

Conclusion : our data show a high mortality rate in elderly patients with hypercapnic respiratory failure and with diagnosis of dementia submitted to NIV. We think that this may be due to a lower compliance to NIV in this population.
Utility of gallium-67 scintigraphy in low-grade non-Hodgkin's lymphoma.
Authors: S Ben-Haim, R Bar-Shalom, O Israel, N Haim, R Epelbaum, M Ben-Shachar, D Gaitini, G M Kolodny, D Front
Journal: Journal of Clinical Oncology (1996)

PURPOSE Low-grade non-Hodgkin's lymphoma (LGNHL) has traditionally been considered non-gallium-avid. The sensitivity of gallium 67 (67Ga) scintigraphy when using modern equipment and techniques in patients with LGNHL was investigated. MATERIALS AND METHODS Fifty-seven consecutive patients with LGNHL underwent 67Ga scintigraphy at initial presentation (n = 40), when tumor progression occurred during treatment (n = 3), and at suspected disease recurrence after continuous clinical remission (CCR) (n = 14). Planar and tomographic images were obtained with either a very large field-of-view or a dual-head digital camera. Of 45 patients with Ga-avid LGNHL, 30 underwent 93 follow-up scans (one to six studies per patient). Scan findings were correlated with clinical and computed tomographic (CT) findings and with patient outcomes. RESULTS 67Ga scintigraphy was positive in 45 of 57 patients (sensitivity, 79%) and in 113 of 164 disease sites (sensitivity, 69%). The sensitivity was higher in the more common types of LGNHL: follicular, predominantly small cleaved cell (FSC), and follicular, mixed small cleaved and large cell (FM) (84% and 91% in patients and 72% and 71% in disease sites, respectively). Sensitivity was lower in patients with mucosa-associated lymphoid tissue lymphoma (MALT) and small lymphocytic lymphoma (SL). Among 28 patients with disease recurrence after CCR (14 with and 14 without baseline studies), 67Ga scan was positive in 25, for a sensitivity of 89% for detection of disease recurrence. CONCLUSION When modern technology is used, 67Ga scintigraphy has good sensitivity in patients with LGNHL. It therefore can be used to monitor response to therapy and to provide early detection of disease recurrence in these patients.
Induction of Endothelial PAS Domain Protein-1 by Hypoxia: Characterization and Comparison With Hypoxia-Inducible Factor-1α
Authors: M.S. Wiesener, H. Turley, W.E. Allen, C. Willam, K.-U. Eckardt, K.L. Talks, S.M. Wood, K.C. Gatter, A.L. Harris, C.W. Pugh, P.J. Ratcliffe, P.H. Maxwell
Journal: Blood (1998)
Subgroup analysis of ECOG2 patients from ROMANA 2: A phase III study of anamorelin in NSCLC patients with cachexia.
Authors: Amy Pickar Abernethy, David Christopher Currow, Lyon L. Gleich, Ying Yan, John Friend, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2014)

6 Background: Cancer anorexia-cachexia syndrome (CACS), often observed in NSCLC patients, is characterized by decreased body weight, mainly lean body mass (LBM), and is associated with worse morbidity and survival. Anamorelin HCl (ANAM), a novel selective ghrelin receptor agonist with appetite-enhancing and anabolic activity, is in development as a treatment of NSCLC CACS. Methods: ROMANA 2 was one of two global, double-blind, Phase III trials assessing ANAM efficacy and safety in NSCLC. Patients with unresectable stage III/IV NSCLC, ECOG 0-2 and cachexia (≥5% weight loss within prior 6 months or BMI &lt;20 kg/m 2 ), were randomized (2:1) to 100 mg ANAM or placebo, given daily orally for 12 weeks. Co-primary endpoints were change from baseline over 12 weeks in LBM (measured by DXA) and in handgrip strength (HGS). Secondary endpoints included change in patient symptoms/concerns regarding anorexia-cachexia and fatigue (via Functional Assessment of Anorexia/Cachexia Treatment [FAACT] and Functional Assessment of Chronic Illness Therapy – Fatigue [FACIT-F]). Safety assessments included lab values and adverse events (AEs). This pre-specified analysis focused on ECOG2 patients. Results: ROMANA 2 (N=495) enrolled 130 ECOG2 patients (N=41 placebo; N=89 ANAM). Subgroup demographics were balanced: median age= 64 yr, male (81.5%), metastatic (74.6%), and prior weight loss &gt;10% (61.5%). In the overall trial, ANAM significantly increased LBM vs placebo (0.75 vs -0.96 kg; p&lt;0.0001) and improved FAACT over 12 weeks (3.48±0.9 vs 1.34±1.0; p=0.0016); change in HGS was not statistically different. In the ECOG2 subgroup, ANAM also significantly increased LBM (0.45 vs -2.66 kg; p=0.0004); there was a trend towards improvement in FAACT and FACIT-F but this was not statistically significant. In the ANAM arm of the ECOG2 subgroup, the most frequent drug-related AE was hyperglycemia (4.5%), with few (1.1%) drug-related Grade ≥ 3 AEs. Conclusions: ANAM treatment for 12 weeks was well tolerated. In patients with ECOG2 performance status, which represents a more severe/fragile population, ANAM improved LBM, as well as anorexia-cachexia and fatigue symptoms/concerns in advanced NSCLC cachectic patients. Clinical trial information: NCT01387282.