tbuckley/cabot-search huggingface dataset:
Targeting ErbB receptor interactions: A phase I trial of trastuzumab and erlotinib in metastatic HER2+ Breast Cancer
Authors: C. D. Britten, M. Pegram, P. Rosen, R. S. Finn, A. Wax, L. Bosserman, L. Gordon, L. S. Lin, R. Mass, D. J. Slamon
Journal: Journal of Clinical Oncology (2004)

3045 Background: ErbB receptors (EGFR, HER2, ErbB3, ErbB4) cooperate through heterodimerization to confer a growth advantage in HER2+ metastatic breast cancer (MBC). Trastuzumab, a monoclonal antibody directed against HER2, improves survival when administered in combination with chemotherapy. In this trial, trastuzumab is combined with the EGFR tyrosine kinase inhibitor erlotinib based on preclinical studies demonstrating synergistic antitumor activity across a range of biologically-relevant concentrations in multiple HER2+ breast cancer cell lines [Finn et al; Proc ASCO 2003]. Methods: This study was performed to determine the toxicity, recommended dose, and pharmacokinetic behavior of escalating doses of continuous daily PO erlotinib in combination with standard-dose weekly IV trastuzumab ( 4 mg/kg loading dose, then 2 mg/kg/wk) in women with HER2+ MBC. Results: 16 patients (14 evaluable) have received 58 four-week courses at the following erlotinib dose levels: 50 mg (6 patients); 100 mg (3 patients); and 150 mg (5 patients). The most common toxicities have been grade 1/2 diarrhea (11 patients), and tolerable grade1/2 rash (10 patients). Two patients at the 150 mg dose level required dose reductions for intolerable grade 2/3 rash. Two patients had reversible decreases in left ventricular ejection fraction: 1 patient at the 50 mg dose level had a decrease from 50–60% at baseline to 40–45% after course 1, constituting a DLT; and 1 patient at the 100 mg dose level had a decrease from 60% to 53% after course 6. Pharmacokinetic analysis is ongoing. Two previously untreated patients at the 150 mg dose level have developed confirmed partial responses, and one heavily pretreated patient, initially treated at 50 mg and subsequently escalated to 100 mg, remains on study with stable disease after over 17 months. Conclusions: Erlotinib combined with trastuzumab provides a well-tolerated, completely targeted therapy with preliminary evidence of anti-tumor activity. A phase II trial in women with previously untreated HER2+ MBC will evaluate the recommended dose level of full-dose daily erolotinib (150 mg/day) plus standard-dose weekly trastuzumab. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech Genentech Genentech Genentech
A new endpoint for the assessment of adjuvant therapy in postmenopausal women with operable breast cancer.
Authors: R D Gelber, A Goldhirsch
Journal: Journal of Clinical Oncology (1986)

Between 1978 and 1981, 463 evaluable postmenopausal patients 65 years of age or younger with operable breast cancer and metastases in axillary lymph nodes were entered in Ludwig Breast Cancer Study III (Ludwig III) and randomly allocated to receive chemoendocrine therapy with cyclophosphamide, methotrexate, 5-fluorouracil, low-dose continuous prednisone, and tamoxifen (CMFp + T) for 12 monthly cycles, or endocrine therapy alone with prednisone and tamoxifen (p + T) for 1 year, or no adjuvant treatment after mastectomy (observation). At 60 months' median follow-up, the 5-year disease-free survival (DFS) rates were 59% for CMFp + T, 41% for p + T, and 31% for observation (P less than .0001), and the 5-year overall survival (OS) rates were 71% for CMFp + T, 64% for p + T, and 59% for observation (P = .16; CMFp + T v observation, P = .07). A new quality of life-oriented endpoint was defined to assist in the selection of therapeutic approach after surgery for postmenopausal patients: the time without symptoms of disease and subjective toxic effects of treatment (TWiST). Despite the larger initial discount due to subjective toxicity with chemoendocrine therapy, by 5 years postmastectomy the net difference in average TWiST for treated patients compared with the observation group was positive and approximately equal for both adjuvant treatment programs. Adjuvant chemoendocrine therapy for postmenopausal women appears to be justified due to an emerging OS advantage and increasing TWiST gained for the treated patients.
Smoking cessation but not inhaled corticosteroids (ICS) can increase histone deacetylase 2 (HDAC2)] in COPD
Authors: SS Sohal, D Reid, A Soltani, S Weston, HK Muller, R Wood-Baker, EH Walters
Journal: European Respiratory Journal (2010)

Introduction: The expression of anti-inflammatory HDAC2 may be reduced in
COPD1 due to increased oxidative stress secondary to airway inflammation. This
may induce resistance to ICS.
Objective: To confirm the extent of suppressed HDAC2 immunostaining within
the airways of COPD; its reversibility with ICS or smoking cessation.
Methods: Endobronchial biopsies (ebb) from current smoking with COPD (CS;
n=15), ex-smokers with COPD (ES; n=17) and normal controls (NC; n=9) were
immunostained for HDAC2. COPD subjects entered a double blind randomised
controlled trial comparing fluticasone propionate (0.5 mg/twice daily) with placebo
for 6 months; ebb were again obtained after treatment and effects of ICS on HDAC2
assessed.
Results: Compared to NC there was normal epithelial HDAC2 staining but signif-
icant reduction in HDAC2 positive cells in the lamina propria (LP) in CS (p=0.02).
However, this was due to a reduction in total LP cells (p = 0.04) and % cell
HDAC2 staining was normal. This total cell change strongly negatively correlated
to smoking history (R = -0.8, p<0.003). There were significantly more HDAC2
positive cells in ES compared to CS (p=0.04), and this was due to an increase in
% cell staining and not increase in total cell numbers. ICS made no difference to
HDAC2 staining.
Conclusions: Our finding suggests that HDAC2 expression is reduced in CS but
due to confounding by changes in cellularity in LP. Quitting does seem to have
a real effect on upregulating HDAC2 at a cell level, but is not affected by ICS.
Prospective long term smoking cessation studies are needed to confirm these
preliminary findings.
Participants perspectives of living with COPD: The role of different groups of health professionals
Authors: Andrew Hardy, Alison Coe
Journal: European Respiratory Journal (2011)

Methodology:  This is a qualitative research study of participants experiences of a pulmonary rehabilitation (PR) programme based in Wakefield, UK. 4 group interviews were carried out in spring 2010 involving 24 participants. 22 had a primary diagnosis of COPD (mean FEV1 1.1 litres, 42% predicted), 1 had lung cancer and 1 was a carer for a participant with COPD. A structured interview included discussion of the roles of different groups of health professionals- general practitioners (GP) and nurse specialists.   Results:  Particpants liked their GP to have good communication skills. Specific examples of good practice were describing illness in a manner which the participant could understand and allowing time to ask questions. Patients appreciated the amount of time they were able to spend with a doctor, liked regular contact with the same GP and disliked waiting for appointments. Participants wanted to feel that something could be done to improve their situation, trusted doctors decision making and rarely asked questions regarding their treatments. Specialist nurses were considered to be more helpful in managing symptoms than GPs. Nurses had more time for patients, were more likely to involve patients in decision making, and showed greater empathy. Some nursing staff were considered to have more specialist knowledge than GPs. Participants described a high degree of trust in nurses decision making and were more comfortable discussing their condition with them.   Summary:  Patients with COPD value good communication skills, expert knowledge, a positive approach and good time management in their health providers. Specialist nurses are able to deliver an effective patient-centred service.
Neoadjuvant chemoradiation (NACRT) and the prognostic effect of surgical margin (SM) status in pancreatic adenocarcinoma (PAC).
Authors: Lora S Wang, John Parker Hoffman, Elizabeth Handorf, Colin T. Murphy, Harry S. Cooper, Steven J. Cohen, Joshua E. Meyer
Journal: Journal of Clinical Oncology (2015)

407 Background: Many studies have associated a R0 resection to have significantly improved survival compared with a R1 resection in PAC. Patients (pts) who undergo NACRT often go to surgery 4-8 weeks after the end of therapy, before the effects of NACRT can be fully manifested. The goal of this study is to evaluate if a positive SM (+SM) after NACRT has the same poor prognosis as a +SM after upfront surgery. Methods: After IRB approval, we retrospectively reviewed all cases of surgically resected PAC at a single institution from Dec 1996 to Jan 2014. Pts were stratified by receipt of NACRT as well as by SM status. We excluded pts treated with palliative intent, metastatic disease at presentation, death within 90 days of surgery, and biliary or ampullary tumors. The primary endpoint was overall survival (OS). We assessed the relationship between pt and tumor variables with treatment/margin combination using Chi-squared tests. OS was examined using Kaplan-Meier curves, and we tested association with treatment/margin using log-rank tests. Results: A total of 213 pts met inclusion criteria; 111 received upfront surgery (group I) with 94 (85%) receiving adjuvant chemotherapy or CRT and 102 received NACRT (group II) with either concurrent 5-fluorouracil (n=18) or gemcitabine (n=84). There were 31 pts with +SM in group I and 29 pts in group II. Pt demographics were balanced. There was more vessel involvement in group II (81%) at diagnosis than group I (11%) (p&lt;0.01) with a trend towards improved OS in group II vs group I (p=0.09). Pathological evaluation revealed more PNI (61% vs 42%, p&lt;0.01) and more lymph node positivity (71% vs 33%, p&lt;0.01) in group I vs group II, respectively. Median OS for group I SM+/SM- and group II SM+/SM- were 15/25 months and 26/32 months respectively. OS is significantly improved with a negative SM (-SM) compared with a +SM (p&lt;0.01). If the SM is positive, pts in group II had improved OS compared with group I (p=0.02). OS was not significantly different for group II +SM vs group I –SM (p=0.34). Conclusions: The negative impact of a +SM on survival is partially mitigated by NACRT. This data further supports the use of NACRT, although it is limited by its retrospective nature and small sample size.
A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission.
Authors: A R Zander, M Keating, K Dicke, D Dixon, S Pierce, S Jagannath, L Peters, L Horwitz, K Cockerill, G Spitzer
Journal: Journal of Clinical Oncology (1988)

From July 1980 to November 1985, 109 patients with acute myelogenous and lymphoblastic leukemia who had reached a complete remission (CR) following induction treatment were assigned to a study comparing marrow transplantation with chemotherapy as a postremission treatment. Sixty-nine patients did not have a human leukocyte antigen (HLA)-identical donor, and therefore served as chemotherapy controls; 40 patients had HLA-identical donors, and therefore were assigned to the transplant arm. Of these, 23 were transplanted in first remission and 17 were not. Ten of these 17 were subsequently transplanted in relapse. Initially, only patients with poor prognosis determined by a predictive model were entered into the study. Subsequently, patients with moderately poor prognosis were admitted. Comparing the chemotherapy group with the patients transplanted in first CR, significant control of leukemia relapse in transplanted patients was seen in the subgroup with acute myelogenous leukemia (AML) (P less than .1), and acute lymphoblastic leukemia (ALL) (P less than .01), in the poor (P = .01) and intermediate subgroup (P = .01), and in the good-prognostic groups (P = .05). The survival was affected significantly in only the poor and intermediate subgroups. The use of predictive models might help to select patients for whom bone marrow transplantation is appropriate in first remission and those for whom bone marrow transplantation can be left as the initial treatment of relapse. Predictive models could further be helpful in comparing studies performed at different transplant centers.
Isosulfan blue major allergic reaction. Case report
Authors: G. E. Cassanello, F. P. Xynos, P. H. Capellino, G. Kohls
Journal: Journal of Clinical Oncology (2005)

894 Background: Major allergic reaction to Isosulfan blue are uncommon but when occurred it could be severe Methods: Case Report Results: Since 1998, 439 patient have subject to sentinel node investigation for vulvar and breast carcinomas. Isosulfan blue was used in all of them. Two patient (0.4%) experienced major allergic reaction to the stain. Case N° 1: 83 years old patient with diagnosis of epidermoid vulvar carcinoma of the clitoris. Anterior hemivulvectomy and bilateral identification of sentinel node using 5 cc of 1% Isosulfan blue in each side (10 mg total) was performed. The dye was injected subdermally adjacent to the tumor. Ten minutes after the injection the patient presented generalized itching, and a micropapular rash in the face, trunk and both extremities, hypotension (>30% decrease of BP). The patient was treated succesfully with adrenaline SC 0.2mg, adrenaline IV drip, diphenhidramine 20 mg IV, hydrocortisone 200 mg IV and dexamethasone 8 mg IV. Case N° 2: 72 years old patient with history of psoriasis and vitiligo was subjected to sentinel node investigation for breast carcinoma using 5 cc of Isosulfan blue 1% (5 mg) injected subdermally. Five to ten minutes later the search of sentinel node was stopped because a > 50% drop in blood pressure, EKG changes (inverted T wave). The patient was succesfully treated with dopamine IV drip, diphenhidramine 40 mg IV and dexamethasone 8 mg IV Conclusions: Major allergy to Isosulfan blue is an uncommon event but it could be life-threating if correct treatment is not started inmediately. No significant financial relationships to disclose.
Twenty-first century genomics for sports medicine: what does it all mean?
Authors: Nick Webborn, H Paul Dijkstra
Journal: British Journal of Sports Medicine (2015)

We can easily be left behind by the explosion in technological developments in medicine—or is it just a sign of getting older? Many of us will remember a time before MRI were readily available, and having to learn what fat suppressed images, T1s and T2s actually meant.

Genomics is another example of a rapidly expanding technological development with major implications for medicine, and even experienced clinicians (many without formal training in molecular biology) are struggling to understand this. It requires learning a whole new language. The sequencing of the 3.2 billion nucleotides that compose the human genome was first completed only in 2003, at an estimated cost of $2.7 billion. At the time, it was simply something of interest, unlikely to influence our working lives any time soon. Now, in just over a decade, it is possible to sequence the whole genome for $1000.

Genomics is finding its place in medicine, from genetic testing for rare disorders to personalised medicine based on our genetic make up ( see page 1517 ). However, the role of most of the genes in the human genome is still unknown.

A ‘snip’ is no longer just a …
Abstract 12136: Nebivolol Enhances the Efficacy of Type 5 Phosphodiesterase Inhibitors to Relax Human Corpus Cavernosum and Penile Arteries from Diabetic Patients with Erectile Dysfunction
Authors: Jose M La Fuente, Juan I Martinez-Salamanca, Argentina Fernandez, Pedro Cuevas, Pepe Cardoso, Harold M Wright, Javier Angulo
Journal: Circulation (2011)

Background: Erectile dysfunction (ED) is highly prevalent among diabetic men. In addition, diabetes is associated with a poorer therapeutic response to conventional therapy for ED, i.e. type 5 phos...
Colour Blindness and Traffic Signals
Authors: Fwe Green
Journal: BMJ (1933)

The danger from colour-blindness may be greatly minimized by a careful selection of the colours used in traffic signals. With the exception of the rare class of the totally colour-blind, all the partially colour-blind recognize some colours with ease and certainty. The colours recognized are different with each class of the colour-blind. A certain variety may fail with one test, but a man who is much more colour-blind may pass it. A man may fail to distinguish a certain  light, but distinguish with ease another,  light which looks exactly the same to the normal-sighted. Another variety may distinguish with ease a  light, but fail to recognize another  light which appears very similar to the normal-sighted. The old terms red blindness, green blindness, and red-green blindness are quite erroneous, and should be discarded, as stated by a committee of the British Association. As is well known, 50 percent of the dangerously colour-blind pass the Wool test. A similar result is found with other tests which are not constructed to detect all varieties of colour-blindness. I have often given a demonstration when I have shown that the candidate will fail with a number of tests and pass completely with several others. A colour-blind person does not guess unless he is in obvious difficulty, and this is at once apparent. Unlike at sea, the motorist is helped by the position of the lights, as he can note the order in which they come on or go off, and his distance from them is comparatively short. Language: en
A Randomized Phase-II Study of BB-10010 (Macrophage Inflammatory Protein- 1) in Patients With Advanced Breast Cancer Receiving 5-Fluorouracil, Adriamycin, and Cyclophosphamide Chemotherapy
Authors: Mark J. Clemons, Ernest Marshall, Jan Dürig, Ken Watanabe, Anthony Howell, David Miles, Helena Earl, Julie Kiernan, Audrey Griffiths, K. Towlson, P. DeTakats, Nydia G. Testa, Mark Dougal, Michael G. Hunter, L. Michael Wood, Lloyd G. Czaplewski, Andrew Millar, T. Michael Dexter, Brian I. Lord
Journal: Blood (1998)
Monitoring tumor markers in serial sera predicts disease failure in lung cancer patients following surgery
Authors: D. Harpole, M. -B. M. Joshi, R. P. Petersen, C. C. Miller, D. Conlon, K. R. Brooks, T. A. D’Amico
Journal: Journal of Clinical Oncology (2005)

7040 Background: Patients with early stage non-small cell lung cancer (NSCLC) who undergo resection have a recurrence rate of 50% at 5 years. A contributing factor to such a high recurrence rate is the propensity for early spread of disease, under-staging at the time of resection and the lack of effective monitoring tools. This study investigates the utility of a panel of tumor markers of invasion and metastasis measured in serial sera following surgery to predict early recurrence. Methods: Prospective cohort study of 225 clinical stage I NSCLC patients who underwent resection from January 1996 to December 2000. Serial serum collections were drawn prior to resection and at 1, 4, 6, 12, 18 and 24 months following surgery. Serum protein levels of vascular endothelial growth factor (VEGF), E-selectin, CD44, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), urokinase plasminogen activator (UPA) and receptor (UPAR) were measured using enzyme-linked immunosorbent assay (ELISA) against a known standard curve. Average monthly change (slope) in each biomarker for each patient, as well as demographic and staging variables, were modeled on recurrence using multiple logistic regression analysis. Cut points in biomarker slope were optimized by c statistic using univariate logistic regression. Results: The median follow-up was 2.7 years, and 87 patients (39%) had recurrent disease. Elevated levels of VEGF and UPAR were associated with increased risk of recurrence, while bFGF was found to be significantly protective after adjusting for stage in multivariable analysis. Conclusions: To date, there have been no studies evaluating the change in the levels of tumor markers collected in serial sera with respect to disease stage, recurrence and cancer-free survival. This study suggests that specific tumor markers collected in serial sera following surgery in patients with NSCLC may serve as a diagnostic tool for detecting early recurrence. No significant financial relationships to disclose.
Intravenous administration of amphotericin B entrapped in liposomes: Induction of high serum levels of TNFα
Authors: J.P. Sculier, J.J. Body
Journal: Annals of Oncology (1991)

The rate of objective response to second-line chemotherapy with cyclophosphamide, adriamycin and vincristine increased from 13% to 55% in two consecutive series of patients with small-cell lung cancer when the therapy was potentiated by amphotericin B (2 mg/kg i.v.) entrapped in liposomes (= ampholiposomes). Patients who received ampholiposomes had a rapid and significant (p less than 0.01) increase of serum TNF alpha concentrations (median value: from less than 10 to 261 pg/mL) followed by a rise in serum neopterin and CRP. No major side effects were observed. Administration of ampholiposomes appeared to be a safe method for obtaining relatively high serum levels of TNF alpha that could potentiate anticancer chemotherapy.
FOLFOXIRI (irinotecan, oxaliplatin, and infusional 5FU/LV) in combination with bevacizumab (BV) in the first-line treatment of metastatic colorectal cancer (mCRC): A phase II study by the G.O.N.O. group
Authors: A. Falcone, G. Masi, F. Loupakis, E. Vasile, A. Ciarlo, D. Cavaciocchi, D. Amoroso, M. Puglisi, E. Fea, I. Brunetti
Journal: Journal of Clinical Oncology (2008)

4031
Alexander Ian Cheyne
Authors: Alison Cheyne
Journal: BMJ (2015)

Alexander Ian Cheyne (“Sandy”) was born in Rangoon, Burma, and educated at Aberdeen Grammar School before studying medicine at Aberdeen University. While at university he played rugby for both Aberdeen and Scottish universities. He completed his house jobs at Aberdeen Royal Infirmary in orthopaedics, followed by medicine at Glasgow Royal Infirmary. He did his national service in the Royal Army Medical Corps, at Depot Crookham, in charge of the …
Influence of iron status in the response to the deferoxamine test.
Authors: J B Cannata, J L Fernández-Martín, B Díaz-López, M Alonso, I Olaizola, G Acuña, C Caramelo, J Alvarez-Grande
Journal: Journal of the American Society of Nephrology (1996)

The study presented here was carried out to evaluate the possible relationship between serum iron and iron transferrin saturation with the response to the deferoxamine test in 86 chronic renal failure patients undergoing hemodialysis. The deferoxamine test was performed as a diagnostic tool for aluminum intoxication. Basal serum aluminum levels correlated with: (1) serum aluminum levels after the infusion of deferoxamine (r = 0.45; P < 0.05); (2) serum iron levels (r = -0.26; P < 0.05), and; (3) iron transferrin saturation (r = -0.33; P < 0.05). The increase in serum aluminum levels after deferoxamine administration (DAI) showed a negative relationship with serum iron levels (r = -0.23; P < 0.05) and iron transferrin saturation (r = -0.26; P < 0.05). The correlations improved when analysis of this study included only those patients with high serum iron levels or high iron transferrin saturation (r = -0.55). Patients with low probability of having aluminum overload (serum iron levels < 40 micrograms/L and DAI < 150 micrograms/L) had significantly higher values of serum iron, iron transferrin saturation, and serum ferritin levels compared with those patients with a high probability of having aluminum overload (serum aluminum levels > 40 micrograms/L and DAI > 150 micrograms/L). The study presented here suggests that patients who have indicators of iron repletion would tend to have lower increases in serum aluminum levels after the challenge with deferoxamine and presumably a higher incidence of false negative results with the deferoxamine test. These findings indicate that iron measurements must be always taken into account when interpreting the deferoxamine test.