tbuckley/cabot-search huggingface dataset:
Patient preferences for oral versus intravenous palliative chemotherapy.
Authors: G Liu, E Franssen, M I Fitch, E Warner
Journal: Journal of Clinical Oncology (1997)

PURPOSE To assess patient preference for oral versus intravenous (i.v.) palliative chemotherapy (CT). A strong preference would be an important quality-of-life issue. PATIENTS AND METHODS A structured interviewer-administered scenario-based questionnaire evaluated incurable cancer patients who would be likely to receive palliative CT in the future. Using probability trade-offs, the preference for route of administration was evaluated against diminishing treatment response. RESULTS Of 103 assessable patients, 92 preferred oral CT, 10 preferred i.v. CT, and one had no preference. Patient preferences were not associated with age, sex, site of primary cancer, or previous CT experiences. Major reasons for preferring oral CT were convenience, problems with i.v. access or needles, and a better CT-taking environment (outside of the clinic). Regardless of initial preference, 70% of patients were not willing to accept a lower response rate and 74% were not willing to accept a shorter duration of response to retain their initial preference. Although 99% of patients had a preference, 39% wanted the specific treatment decision made primarily by their physicians, 38% primarily by themselves, and 22% shared equally. CONCLUSION Patients with incurable cancer have a clear preference for oral CT, but are generally not willing to sacrifice efficacy for their preference. Almost 40% of patients did not want to make final treatment decisions themselves.
Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome
Authors: Emanuela Pasciuto, Tariq Ahmed, Tina Wahle, Fabrizio Gardoni, Laura D’Andrea, Laura Pacini, Sébastien Jacquemont, Flora Tassone, Detlef Balschun, Carlos G. Dotti, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, Ulrike C. Müller, Monica Di Luca, Bart De Strooper, Claudia Bagni
Journal: Neuron (2015)
Evaluating the FVC-reference equation for female
Authors: Jellien Makonga-Braaksma, Remco Boksem, Pim Dalinghaus
Journal: European Respiratory Journal (2011)

Introduction:  At World Spirometry Day we measured lungfunction in hospital staff (n=99, m= 40, f=59) in Amersfoort, the Netherlands. We were struck by the high scores in FVC in the female group. In the group of healthy, never-smoking female (n=36) (Ages 18-64) we discovered that mean FVC was 114% pred. Other studies about this subject show that reference values for male have not enough correction for aging, but are quite correct for height.   Aim:  Understand which element of the reference-equation for female doesn9t fit properly, and search for alternatives.   Methods:  First we analysed the ECCS reference equation for FVC in female: 4,43H – 0,026A – 2,89 (H=height in m, A=Age in y) (ERJ 1993.) Then we made a statistical analysis for FVC% pred. (y) and age (x) and FVC% pred. (y) and height (x).   Analysis:  The statistics show that female from 18-44 ys. have a lower FVC% pred.(n=18,mean FVC = 106%pred) than female from 45-64 ys.(n=18, mean=120% pred.) We see that female between ages 45-64 with a moderate height (160-170cm) have the highest scores. There is a linear relation between age and FVC% pred.(p 120%) we see a relation between height and FVC% pred.(p   Conclusion/Discussion:  Aging of the lung should be related to the volume of that specific lung. We have high expectations of the new reference equations introduced by taskforce Global Lungs Initiative. In the clinical setting there9s a risk of underestimating restrictive patterns in tiny elderly female when applying the ECCS reference equations.
Usability testing of a new mixed mode ventilator
Authors: Sahisha Ketheeswaran, Etienne Veschambre, Dion Martin, June Mendoza, Julia Lord, Alison Wimms
Journal: European Respiratory Journal (2014)

Aim : Due to the inherent complexity of ventilators, operation is often challenging for users. The aim of this test was to evaluate the usability of a new mixed mode life support ventilator (Astral, ResMed Ltd).

Methods : Participants were asked to complete several realistic task based scenarios which evaluated the ventilator core operating functions, for example 'setting up the ventilator for invasive ventilation with a leak circuit on an adult patient'. A total of 307 different tasks were identified for evaluation, and each task was required to be tested by a minimum of 8 participants, or 15 participants for safety critical tasks. Participants were also asked to respond to 'emergency' situations during which ventilator alarms and patient conditions were simulated.

Results : 90 participants (55 clinicians, 27 lay operators, 8 biomedical technicians) completed the evaluation. Participants' ages ranged from 18 to >70 and participants level of experience ranged from no experience to >20 years. All safety related tasks and core ventilator tasks were successfully completed by participants. Areas which participants found most difficult involved circuit set-up. Areas which participants rated as having the highest usability (an average usability score of 10/10) were: conducting alarms tests; changing alarms volumes; and identifying the activation of the remote alarm. Results from this evaluation were fed back to the ventilator design team to be used for future design refinement and/or modifications to education materials.

Conclusion : During this evaluation the ventilator was able to be used safety, as intended, with strong overall usability ratings from participants particularly concerning the testing, and activation of alarms.
Aberrant hypermethylation in primary tumours and sentinel lymph node metastases in paediatric patients with cutaneous melanoma
Authors: K.T. Huynh, Y. Takei, C. Kuo, R.A. Scolyer, R. Murali, K. Chong, L. Takeshima, M-S. Sim, D.L. Morton, R.R. Turner, J.F. Thompson, D.S.B. Hoon
Journal: British Journal of Dermatology (2012)

Debate on how to manage paediatric patients with cutaneous melanoma continues, particularly in those with sentinel lymph node (SLN) metastases who are at higher risk of poor outcomes. Management is often based on adult algorithms, although differences in clinical outcomes between paediatric and adult patients suggest that melanoma in paediatric patients differs biologically. Yet, there are no molecular prognostic studies identifying these differences.We investigated the epigenetic (methylation) regulation of several tumour-related genes (TRGs) known to be significant in adult melanoma progression in histopathology(+) SLN metastases (n = 17) and primary tumours (n = 20) of paediatric patients with melanoma to determine their clinical relevance.Paediatric patients (n = 37; ≤ 21 years at diagnosis) with American Joint Committee on Cancer stage I-III cutaneous melanoma were analysed. Gene promoter methylation of the TRGs RASSF1A, RARβ2, WIF1 and APC was evaluated.Hypermethylation of RASSF1A, RARβ2, WIF1 and APC was found in 29% (5/17), 25% (4/16), 25% (4/16) and 19% (3/16) of histopathology(+) SLNs, respectively. When matched to adult cutaneous melanomas by Breslow thickness and ulceration, hypermethylation of all four TRGs in SLN(+) paediatric patients with melanoma was equivalent to or less than in adults. With a median follow-up of 55 months, SLN(+) paediatric patients with melanoma with hypermethylation of > 1 TRG vs. ≤ 1 TRG had worse disease-free (P = 0·02) and overall survival (P = 0·02).Differences in the methylation status of these TRGs in SLN(+) paediatric and adult patients with melanoma may account for why SLN(+) paediatric patients have different clinical outcomes. SLN biopsy should continue to be performed; within SLN(+) paediatric patients with melanoma, hypermethylation of TRGs can be used to identify a subpopulation at highest risk for poor outcomes who warrant vigilant clinical follow-up.
Antibody targeting in metastatic colon cancer: a phase I study of monoclonal antibody F19 against a cell-surface protein of reactive tumor stromal fibroblasts.
Authors: S Welt, C R Divgi, A M Scott, P Garin-Chesa, R D Finn, M Graham, E A Carswell, A Cohen, S M Larson, L J Old
Journal: Journal of Clinical Oncology (1994)

PURPOSE To define the toxicity, imaging, and biodistribution characteristics of iodine 131-labeled monoclonal antibody F19 (131I-mAbF19). MAbF19 recognizes the fibroblast activation protein (FAP), a cell-surface glycoprotein not present in most normal tissues, but abundantly expressed by reactive stromal fibroblasts of epithelial cancers, including more than 95% of primary and metastatic colorectal carcinomas. PATIENTS AND METHODS 131I-mAbF19 was administered intravenously to 17 patients with hepatic metastases from colorectal carcinoma who were scheduled for resection of localized metastases or insertion of hepatic artery catheter for regional chemotherapy. Seven to 8 days before surgery, patients received 131I-mAbF19 at three dose levels, with at least four patients entered at each level. RESULTS No toxicity associated with intravenous 131I-mAbF19 administration was observed. Tumor images were obtained on planar and single-photon emission tomography (SPECT) scans in 15 of 17 patients with hepatic metastases, tumor-infiltrated portal lymph nodes, and/or recurrent pelvic disease. The smallest lesion visualized was 1 cm in diameter. The optimal time for tumor imaging was 3 to 5 days after 131I-mAbF19 administration. The use of image registration techniques allowed precise anatomic localization of 131I-mAbF19 accumulation. Immunohistochemical analysis of biopsy tissues showed expression of FAP in the tumor stroma (but not in normal liver) in all patients studied and confirmed that the FAP-positive tumor stromal fibroblasts were interposed between the tumor capillaries and the malignant colon epithelial cells. At the time of surgery, tumor-to-liver ratios up to 21:1 and tumor-to-serum ratios up to 9:1 were obtained. The fraction of the injected 131I-mAbF19 dose per gram tumor (%ID/g tumor) localized to hepatic metastases at the time of surgery ranged from 0.001% to 0.016%. CONCLUSION The FAP tumor fibroblast antigen is highly expressed in primary and metastatic colorectal carcinomas and shows limited expression in normal adult tissues. This highly selective expression pattern allows imaging of colorectal carcinoma lesions as small as 1 cm in diameter on 131I-mAbF19 scans. Because of the consistent presence of FAP in the stroma of epithelial cancers and the accessibility of FAP-positive tumor stromal fibroblasts to circulating monoclonal antibodies (mAbs), this study suggests possible diagnostic and therapeutic applications of humanized mAbF19 and mAbF19 constructs with novel immune and nonimmune effector functions.
Surveillance for Recurrent Head and Neck Cancer Using Positron Emission Tomography
Authors: Val J. Lowe, James H. Boyd, Frank R. Dunphy, Han Kim, T. Dunleavy, Brian T. Collins, David Martin, Brendan C. Stack, Chris Hollenbeak, J.W. Fletcher
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P = .013) or PE (P = .002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.
Transient Graft-Versus-Host Reaction in the Treatment of Leukemia in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Milivoj Boranić
Journal: JNCI Journal of the National Cancer Institute (1968)

Inbred RF mice, each bearing a transplanted myeloid leukemia, received 530 rads of X rays and then injections of C57BL spleen cells (10–60 × 106) and bone marrow cells (40–60 × 106). Most of these animals died with clinical and histological signs of secondary disease. Leukemia incidence, as judged by morphological criteria, varied with the spleen cell dose and ranged between 50% and 0. The severity of the secondary disease could be diminished, without recurrence of leukemia, by the immunosuppressive agents cyclophosphamide and heterologous antilymphocyte serum. Administration of recipient-type hematopoietic cells and blood after the course of cyclophosphamide abolished the chimeric state and prevented secondary disease, without recurrence of the leukemia. It is concluded that, in the experimental system used, permanent chimerism and the chronic graft-versus-host reaction are not necessarily prerequisite to the suppression of a transplanted leukemia.
Is there evidence that chemotherapy is of benefit to patients with carcinoma of the prostate?
Authors: I F Tannock
Journal: Journal of Clinical Oncology (1985)

Most patients with metastatic carcinoma of the prostate have osteoblastic bone metastases and nonmeasurable pelvic disease. These features cause patients to be at high risk for myelosuppression after cytotoxic chemotherapy and make it difficult to evaluate response to treatment. A critical review of larger trials that have sought to assess the role of chemotherapy in treatment of carcinoma of the prostate leads to the following conclusions: (1) Although the aim of treatment is palliation, most trials have tried to evaluate tumor response rather than the more appropriate endpoints of quality and quantity of survival for all treated patients. (2) Criteria that have been used for tumor response are variable and contain large inherent errors; most patients who are labeled as "responders" are described as being "objectively stable," but this category may be a manifestation of slowly progressive disease rather than a response to treatment. (3) There is no evidence that chemotherapy causes a meaningful prolongation of survival. (4) Chemotherapy adds considerable toxicity, and reported trials have not adequately assessed its overall impact on quality of life. Because of these factors there is little evidence that chemotherapy provides palliation for patients with prostatic carcinoma, and it should not be regarded as part of standard management. Selected patients who are symptomatic and no longer responding to hormones may be considered for trials of chemotherapy. Future trials should randomize patients to chemotherapy or supportive care, with assessment of quality and quantity of survival for all randomized patients by an observer who is unaware of the treatment.
Validation of the four -variable screening tool in a European population for assessing obstructive sleep apnea syndrome
Authors: Athanasia Pataka, Nikolaos Chavouzis, Katalin Fekete Passa, Asimina Paspala, Evdokia Sourla, Eleni Vaitsi, George Kalamaras, Georgia Pitsiou, Vasilios Bagalas, Ioannis Stanopoulos, Paraskevi Argyropoulou
Journal: European Respiratory Journal (2013)

Background: The 4-Variable screening tool (4-V) was developed and validated in Japan from Takegami et al as a tool for the identification of Obstructive Sleep Apnea Syndrome (OSAS).  Objectives: To evaluate the ability of the 4-V to estimate the incidence of OSAS as measured by Apnea Hypopnea Index (AHI) in a European Population as the antropometric data differ between race (caucasian-asian).  Methods: The risk of OSAS was calculated by the 4-V tool in 1057 patients visiting a sleep clinic in Greece. All patients underwent polysomnography (PSG).  Results: The mean age of patients (73.8%male) was 52±14 yr, BMI 32.9±7 kg/ m2, neck circumference 41.75±4.3 cm, Epworth Sleepiness Scale (ESS) 11.5±5.4, Apnea Hypopnea Index (AHI) 32.7±26.5/h, Oxygen Desaturation Index (ODI) 37.7±29.6 and 4-V score 13.3±2.5. OSAS was diagnosed with PSG in 849(80.3%) patients: 13.6% mild, 19.1% moderate,47.6% severe. By 4-V (≥14) 45.1% (477) of patients were classified as being at high risk of OSAS. The sensitivities of 4-V for AHI ≥5, ≥ 15 and ≥ 30 were 50.7%, 54.9% and 61%, respectively; the specificities 78%,74.4%,69.3%; the positive predictive values 90.3%, 81.1%, 64.3%; the negative predictive values 27.9%, 45.1% and 66.2%. The area under the ROC curve at AHI≥ 5 was 0.68.  Conclusions: In a European population 4-V may miss cases suffering from OSAS (relatively low sensitivity) but it has good specificity classifying fewer normal persons as high-risk for OSAS.
Intercalated Cell Subtypes in Connecting Tubule and Cortical Collecting Duct of Rat and Mouse
Authors: JIN KIM, YOUNG-HEE KIM, JUNG-HO CHA, C. CRAIG TISHER, KIRSTEN M. MADSEN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. At least two populations of intercalated cells, type A and type B, exist in the connecting tubule (CNT), initial collecting tubule (ICT), and cortical collecting duct (CCD). Type A intercalated cells secrete protons via an apical H + - ATPase and reabsorb bicarbonate by a band 3-like Cl - /HCO 3 - exchanger, AE1, located in the basolateral plasma membrane. Type B intercalated cells secrete bicarbonate by an apical Cl - /HCO 3 - exchanger that is distinct from AE1 and remains to be identified. They express H + -ATPase in the basolateral plasma membrane and in vesicles throughout the cytoplasm. A third type of intercalated cell with apical H + -ATPase, but no AE1, has been described in the CNT and CCD of both rat and mouse. The prevalence of the third cell type is not known. The aim of this study was to characterize and quantify intercalated cell subtypes, including the newly described third non A-non B cell, in the CNT, ICT, and CCD of the rat and mouse. A triple immunolabeling procedure was developed in which antibodies to H + -ATPase and band 3 protein were used to identify subpopulations of intercalated cells, and segment-specific antibodies were used to identify distal tubule and collecting duct segments. In both rat and mouse, intercalated cells constituted approximately 40% of the cells in the CNT, ICT, and CCD. Type A, type B, and non A-non B intercalated cells were observed in all of the three segments, with type A cells being the most prevalent in both species. In the mouse, however, non A-non B cells constituted more than half of the intercalated cells in the CNT, 39% in the ICT, and 22% in the CCD, compared with 14, 7, and 5%, respectively, in the rat. In contrast, type B intercalated cells accounted for only 8 to 16% of the intercalated cells in the three segments in the mouse compared with 26 to 39% in the rat. It is concluded that striking differences exist in the prevalence and distribution of the different types of intercalated cells in the CNT, ICT, and CCD of rat and mouse. In the rat, the non A-non B cells are fairly rare, whereas in the mouse, they constitute a major fraction of the intercalated cells, primarily at the expense of the type B intercalated cells.
Phase I and plasma pharmacokinetic study of infusional fluorouracil combined with recombinant interferon alfa-2b in patients with advanced cancer.
Authors: L L Danhauser, J H Freimann, T L Gilchrist, J U Gutterman, C Y Hunter, A C Yeomans, A B Markowitz
Journal: Journal of Clinical Oncology (1993)

PURPOSE Enhanced fluorouracil (FUra) cytotoxicity caused by recombinant interferon alfa-2b (rIFN-a) has been reported, but the mechanism, optimal dose, and schedule remain unknown. Therefore, a phase I and pharmacokinetic study of FUra with escalating doses of rIFN-a was initiated. PATIENTS AND METHODS FUra (750 mg/m2/d) was given by continuous intravenous (IV) infusion for 5 days. rIFN-a (0.1 to 15 x 10(6) U/m2/d) was given subcutaneously (SC) daily for 5 days concurrent with FUra. Courses were repeated every 14 to 21 days. Forty-four patients were enrolled; 39 received at least two courses. During the first course of therapy, FUra levels before and after administration of rIFN-a were quantitated in 26 patients by high-pressure liquid chromatography. RESULTS The maximum-tolerated dose of rIFN-a was 10 x 10(6) U/m2/d. Stomatitis was dose-limiting. Three partial and five minor responses occurred. Interpatient pharmacokinetics showed that rIFN-a did not alter steady-state plasma concentration (Css; range, 0.77 +/- 0.35 mumol/L to 1.85 +/- 0.48 mumol/L), elimination half-life (t1/2; mean, 9.7 +/- 4.3 minutes), area under the concentration-versus-time curve (AUC; range, 93 to 224 mumol/L x hours), total-body clearance (CI; range, 1,172 to 3,236 mL/min), or volume of distribution (range, 11.9 to 49.2 L) of FUra. Intrapatient data evaluation revealed a dose-independent effect of rIFN-a. The mean FUra Css after rIFN-a administration (1.31 mumol/L) was greater than that before rIFN-a administration (1.02 mumol/L, P &lt; .0001). FUra Cl after rIFN-a administration was reduced by 20% to 35% compared with use of FUra alone (P &lt; .0001). Patients with a greater than 20% decrease in FUra Cl had a fourfold greater incidence of diarrhea. CONCLUSION rIFN-a reduces FUra Cl and, consequently, increases FUra-associated toxicity. Phase II studies of FUra and rIFN-a seem to be warranted.
Epidemiology and clinical management of spinal tuberculosis (TB) at a south-east London hospital
Authors: Pretin Davda, Tehmina Bharucha, Jagan Murugachandran, Paramita Palchaudhuri
Journal: European Respiratory Journal (2014)

Background: Spinal TB presents a challenging diagnosis with potentially devastating outcomes. NICE guidelines [CG117] suggest 6 months of treatment (12 months if cord compression) but data on spinal TB in UK is limited. Aim: To review the epidemiology + clinical management of Spinal TB at Queen Elizabeth Hospital, London. Methods: A retrospective study was performed on spinal TB patients from 2008-2012. Results: 34 patients, mean age 43 years, 22(65%) male. All patients had back pain; 24 (71%) had focal neurology; 15(44%) had constitutional symptoms (fevers + weight loss). On average patients had symptoms for 8.3 months prior to diagnosis. Sites affected: 22(65%) thoracic, 16(47%) lumbar and 4(12%) cervical spine. Commonest MRI abnormalities: 28(82%) Para-vertebral abscesses, 21(62%) vertebral body collapse, 15(44%) epidural abscesses, 13(38%) cord compression. Diagnostic sampling (image guided/surgical) was performed in 29 patients. 10/29 (34%) were smear +ve and 20/29 (69%) were culture +ve; 10/17(59%) histology was +ve for Granulomas. Average treatment duration was 11.9 months. 16 (47%) required steroid therapy in addition to anti-TB medications; 6 (19%) required surgery. Average time for improvement on imaging (MRI/CT scan) was 9.7 months. 29 patients (97%) improved clinically with TB treatment, 12 (36%) had ongoing symptoms post treatment and 6 (18%) remained with disability. Conclusions: Despite diagnostic delay, good diagnostic samples can be obtained with appropriate imaging. Treatment duration (+ time to resolution on MRI scans) was longer than NICE recommends. There continues to be long-term disability and clinicians should be more alert to spinal TB presentation.