tbuckley/cabot-search huggingface dataset:
Effect of unilateral lingual paralysis on swallowing and breathing coordination
Authors: Yacine Ouahchi, Jean Paul Marie, Eric Verin
Journal: European Respiratory Journal (2011)

Introduction: The tongue play an important role in swallowing, phonation and respiration. A motor lingual deficit is seen in many neurological disorders. However, its implication on swallowing and breathing coordination remain unknown. The aim of this work was to study the ventilatory pattern during swallowing in rat with unilateral tongue paralysis.

Methods: The study was carried out on 10 wistar rats. Respiratory variables in unrestrained and healthy rats were measured during water swallowing using whole-body plethysmography. This procedure was repeated for all rats before and after unilateral section of hypoglossal nerve (XII). Parameters studied were swallowing frequency and occurrence during inspiration or expiration, tidal volume (VT), total time of ventilatory cycle (TT) and respiratory drive (VT/TI).

Results: A difficulty of leaking was observed in all rats after unilateral hypoglossal nerve section. The main finding was a decrease of respiratory rhythm and ventilatory drive during swallowing after hypoglossal nerve section. Swallowing rate (17±5/15sec) and occurrence in phases of respiratory cycles did not change.

Conclusion: This study demonstrated that swallowing difficulties and aspiration decrease ventilatory drive during swallowing that can be considered as a mechanism neurologically determined to protect the pulmonary function.
Survival with surgical versus medical treatment of patients with bowel obstruction secondary to ovarian cancer recurrence: A 15-year experience
Authors: A. Al-Niaimi, B. Manuelli, N. Safdar, R. Chappell, S. Seo, D. Kushner, J. Connor, E. Hartenbach
Journal: Journal of Clinical Oncology (2009)

e16515 Background: To compare the impact of surgical versus medical management on the survival of patients presenting with small bowel obstruction (SBO) secondary to recurrent ovarian cancer. Methods: The Institutional Review Board approved a retrospective chart review of all patients with SBO due to recurrent ovarian cancer at the University of Wisconsin Hospital between January 1, 1992, and December 31, 2007. The data abstracted from patient charts included demographics, primary cancer characteristics, detailed clinical information at the time of SBO, management strategy, and outcome. Univariate analysis was performed with Cox proportional hazard model and Kaplan-Meier curves were generated for survival. Results: 71 patients met our search criteria, 6 were excluded because of a paucity of medical information. Of the 65 patients in our study, the median age was 53 years. 86% of the patients had stage III/IV ovarian cancer, while 14% had stage I/II. The median time from tumor recurrence to bowel obstruction was 17 months. 41% of patients presented with high grade bowel obstruction while 69% were low grade. 36 (55%) of patients underwent surgery for management of bowel obstruction and the remaining 29 (45%) were managed conservatively with various medical approaches. Two-year survival for the surgically managed patients was 38% compared to 18% for those who received medical treatment (p = 0.07). There was no difference in survival for patients based on histology (p = 0.38), grade (p = 0.077), grade of SBO (p = 0.56). Patients with stage I/II had a median survival of 50 months versus stage III/IV at 3.5 months (p = 0.01). Median survival for patients without ascites at time of SBO was 9.5 months while those with ascites was 3 months (p = 0.0004). Patients without abdominal or pelvic mass on CT had a median survival of 60 months; patients with any mass noted had a median survival of 3.6 months; patients with liver and lung metastases was 3 months (p = 0.001). Conclusions: In patients with bowel obstruction due to ovarian cancer recurrence; early stage at diagnosis, the absence of ascites, and lack of abdominal/pelvic mass or distant metastases significantly lengthens survival. There is a trend towards the superiority of surgical management in these patients. No significant financial relationships to disclose.
Adjuvant trastuzumab (T) therapy in HER2+ breast cancer after ASCO 2005: Patients’ attitudes and immediate economic burden
Authors: S. M. Benn, G. Jha, T. W. Ratliff, K. Spiers, R. Baskin, F. Yunus, R. Osarogiagbon, B. Boston, S. Minhas, M. Jahanzeb
Journal: Journal of Clinical Oncology (2006)

10565 Background: Data from 3 large randomized trials documenting the efficacy of T in the adjuvant setting were reported at ASCO 2005, and subsequently published in NEJM 2005; 353: (16) pp 1659–72 and 1673–1684 . We decided to offer T, and attempted to assess patients’ characteristics that influence its acceptance, in a subgroup of HER2 + patients that had already completed adjuvant chemotherapy at our institution within 12 months prior to these reported results. Methods: Using Electronic Medical Records (OpTx, Canada), we identified HER2+ breast cancer patients who had completed adjuvant therapy within the prior 12 months and administered an informational synopsis about the study results. They then completed a questionnaire, including their demographic information, that established their understanding of the data and documented their decision to receive or to not receive adjuvant T as an afterthought. Results: We identified 1442 breast cancer patients in Optx that were seen at UTCI for initial or follow up visits between May 2004 and May 2005. Those with 3 or fewer visits within the last year and those who received no chemotherapy (n = 770) were excluded. Of the remaining 672 patients, only 104 (15%) had documented HER2+ disease. Fourteen HER2+ patients had metastatic disease, while 84 patients, though HER2+, had either completed adjuvant chemotherapy greater than 12 months prior or were currently receiving adjuvant therapy or T, and/or had other reasons to not be suitable for T. Six patients qualified for this study; 5 decided to receive adjuvant T and 1 chose not to because she perceived the additional benefit to be minimal. Conclusions: While our sample size was too small in the end to draw conclusions about patients’ attitudes towards new data on adjuvant T, we were struck by the small number of patients who could be offered T as an afterthought despite our large patient volume. The magnitude of the perceived economic burden and its imminence after the release of these data may have been overestimated. [Table: see text]
Circulating tumor cells in patients with metastatic urothelial cancer
Authors: M. I. Milowsky, N. M. Ishill, J. Riches, M. Fleisher, A. Trout, A. Valentini, M. G. Boyle, D. F. Bajorin
Journal: Journal of Clinical Oncology (2008)

16054 Background: For the majority of patients (pts) with metastatic urothelial cancer (UC), there is no curative therapy and only a modest survival benefit associated with systemic chemotherapy. Blood-based biomarkers may improve treatment selection by identifying patients in whom a specific therapy is likely to provide the most benefit. Antibody-capture technologies have successfully been used to isolate circulating tumor cells (CTC) in other malignancies and this pilot study was designed to evaluate CTCs in pts with metastatic UC. Methods: Pts (N=24) with metastatic UC were evaluated. Peripheral blood was evaluated for CTCs by using the CellSearch system and positive CTC assays required cells staining for both EpCAM (epithelial cellular adhesion molecule) and nuclear DAPI and negative staining for CD45. We assessed patients for the association between CTC counts, sites of disease and number of metastatic sites. Results: The median age was 68 years (range: 51–83). Primary sites of UC included bladder (14 pts) and renal pelvis/ureter (10 pts). Patterns of metastatic spread included lung in 11 pts (46%), liver in 7 pts (29%), bone in 10 pts (42%), and lymph nodes in 12 pts (50%). 16 pts had ≥ 2 sites of metastases. 19 pts received ≥ 1 chemotherapy and/or investigational agent (median = 1 prior treatment regimen; range 0–5). 14/24 (58%) pts had a positive assay. CTC counts ranged up to 87 cells per 7.5 mL of blood. 9 pts (38%) had ≥ 5 CTCs. Higher median numbers of CTCs were seen in pts with bone metastases compared to pts without bone metastases (8 vs. 0.5, p=0.12, Wilcoxan rank sum test) and in pts with liver metastases compared to pts without liver metastases (8 vs. 1, p=0.14) while higher CTCs were seen in more pts without lung metastases compared to pts with lung metastases (6 vs. 0, p=.15). More CTCs were seen in pts with ≥ 2 sites of metastases as compared to those with ≤ 1 site of metastases (6 vs. 0.5, p=0.09). Conclusions: CTCs can be detected using antibody-capture technology in pts with metastatic UC. Analysis of this pilot study is limited by the small sample size, however, additional pts will be evaluated to determine if significant associations exist between CTCs and disease sites and other parameters. No significant financial relationships to disclose.
Abstract 10584: The Effect of Nifekalant Hydrochloride for Patients With Refractory Ventricular Fibrillation Outside the Hospital (A SOS-KANTO 2012 Observational Study Interim Report)
Authors: Mari Amino, Sadaki Inokuchi, Koichiro Yoshioka, Yoshihide Nakagawa, Kazuo Umezawa, Yoshio Tahara, Ken Nagao, Arino Yaguchi, Naoto Morimura
Journal: Circulation (2013)

BACKGROUND: There is insufficient evidence that intravenous amiodarone during cardiopulmonary resuscitation (CPR) improve survival to discharge for patients with out-of-hospital cardiac arrest (OHC...
Modulation of the antitumor effect of methotrexate by low-dose leucovorin in squamous cell head and neck cancer: a randomized placebo-controlled clinical trial.
Authors: G P Browman, M D Goodyear, M N Levine, R Russell, S D Archibald, J E Young
Journal: Journal of Clinical Oncology (1990)

Randomized trials comparing high-dose methotrexate (HDMTX) plus leucovorin (LV) with standard-dose methotrexate (SDMTX) have not detected a therapeutic advantage for the HDMTX arm despite compelling evidence from experimental systems. We hypothesized that these negative trials might reflect modulation of the antitumor effect of methotrexate (MTX) by LV. To test this we randomized 61 patients with locally advanced and recurrent squamous cell head and neck cancer to receive SDMTX (40 mg/m2 weekly for 8 weeks) and either LV or placebo "rescue" starting 24 hours later. Of the 61 randomized patients, there were protocol violations in two cases, leaving 59 patients evaluable for response using standard criteria, and for toxicity using the Eastern Cooperative Oncology Group (ECOG) scale. Of the 29 patients randomized to MTX plus LV, there were five responders (17.2%) compared with 11 of 30 (36.7%) patients randomized to MTX plus placebo (P = .047). Response was influenced independently by age, gender, and by previous treatment. Toxicity overall was more severe in patients randomized to MTX plus placebo (P = .016). This was accounted for primarily by differences in toxicities related to bone marrow function (neutrophil and platelet counts), stomatitis, and elevations of liver function tests. MTX therapy was more often interrupted for toxicity in the placebo group (P = .007) and discontinued for progressive disease in the LV group (P = .07). These results indicate that at the doses of MTX and LV used, LV modulates the antitumor effect as well as the toxicity of MTX in patients with head and neck cancer.
Randomized phase II study of low (100mg) versus intermediate (400mg) doses of thalidomide (Thal) plus DTIC in metastatic melanoma (MM)
Authors: R. Von Moos, R. Dummer, R. Inauen, T. Ruhstaller, S. Meier, J. Skalsky, F. Hitz, W. Korte, T. Cerny, S. Gillessen
Journal: Journal of Clinical Oncology (2006)

8048 Background: Single agent DTIC is the standard therapy for MM. In an effort to improve the response rate (DTIC 7–13%), Thal, a molecule with antiangiogenic effect was added in two different dosages to DTIC. Methods: Eligibility: Stage IV MM, ECOG performance status 0–2, no prior treatment with DTIC or Thal. Design: Randomized multicenter phase II Bryant and Day 2-stage optimal design with 20 patients (pats) per arm. Treatment regimens: DTIC 200mg/m 2 d1–5 q3w plus Thal (100 versus 400mg per day). Responses were assessed every two cycles. Endpoints: Toxicity, feasibility, response rate (RR) and time to treatment failure (TTF). Results: 26 pats (12 male/ 14 female) at a median age of 58 years (range 24–82) with stage IV melanoma (M1a-2, M1b-2, M1c-22) were enrolled between 2001–2005 and received a median of 4 cycles (1–6). All the pats were evaluated for toxicity, 25 (96%) were assessable for objective response (WHO criteria). The overall response rate of the evaluable patients was 27% (100mg, RR 25%; 400mg, RR 33%), one patient (4%) had a complete response, 6 pats (23%) had a partial response, 11 pats had stable disease (42%), and 7 pats (27%) progressed. The median TTF was 5.2 months. Using NCI 2.0 Common Toxicity Criteria, grade 3 haematological toxicity was 12% (anemia-1, leucopenia-1, thrombocytopenia-1). Cumulative non-haematological toxicity grade 3/4 was 35% including fatigue in 5 pats (all on 400mg Thal arm), thromboembolic events in 2 (1 each treatment arm) and bleeding in 2 (1 cerebral). Polyneuropathy and constipation were a minor problem (no grade 3/4). The 400mg Thal arm was stopped according to the protocol because of intolerable fatigue in 5 out of 6 patients. Two of the first 14 pats suffered from pulmonary embolism. Thromboprophylaxis with low molecular weight heparin (LMWH) was mandatory after an amendment . Thereafter no thromboembolic events were seen but one fatal cerebral bleeding occurred in one patient. Conclusions: 400mg Thal in combination with DTIC was not feasible due to toxicity. 100mg Thal was well tolerated and showed significant clinical activity. Using our low dose Thal regimen prophylactic LMWH is necessary to prevent severe thromboembolic events. No significant financial relationships to disclose.
Proliferative Activity of Human Granulocytes, as Estimated Quantitatively by &lt;italic&gt;In Vitro&lt;/italic&gt; Colony Formation
Authors: John D. Northup, M.D., Joan M. Bull, M.D., Paul P. Carbone, M.D.
Journal: JNCI Journal of the National Cancer Institute (1972)

With methylcellulose-enriched medium and colony-stimulating (actor prepared from human-embryo kidney cells, an average of 2.4 colonies/10,000 marrow nucleated cells plated can be formed from marrows of normal subjects. Colony formation was markedly reduced in plated marrows from patients with acute leukemia in relapse and aplastic anemia. The proportion of granulocyte precursors in the marrow and the number of colonies in vitro produced were linearly related. Marrow from normal volunteers produced 6 colonies/10,000 granulocyte precursors (cells younger than metamyelocytes). As many as 126 colonies/10,000 granulocyte precursors were cultured from marrow of patients with acute leukemia recovering from chemotherapy. By use of nucleated cell count of the marrow aspirate and colony production, the number of colonies/ml could be determined. The median and range from 10 normals were 12,000 colonies/ml (2,000–25,000). The kinetics of marrow granulocyte function could be studied serially by use of calculations of colony formation, colonies/10,000 granulocyte precursors, and the nucleated cell count in patients with acute lymphocytic leukemia undergoing treatment.
Nonmutational Alteration in Glucocorticoid Sensitivity of Lymphosarcoma P1798&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J M Davis, A K Chan, E A Thompson
Journal: JNCI Journal of the National Cancer Institute (1980)

The sensitivity of lymphosarcoma P1798 to glucocorticoids varied as a function of growth conditions. Cells grown in the ascitic fluid were very sensitive to cortisol inhibition of tritiated thymidine ([3H]dThd) incorporation. When ascites cells were inoculated sc into BALB/c mice receiving daily injections of 2 mg cortisol, tumors did not form. However, as tumors grew subcutaneously in control mice, glucocorticoid sensitivity decreased to the arrested by cortisol injection. Cortisol also did not inhibit incorporation of [3H]dThd in cells prepared from large subcutaneous tumors. Measurement of cytoplasmic receptors in cell-free extracts revealed that both ascites and subcutaneous tumor cells contained about 11-12 x 10(4) glucocorticoid binding sites per cell. Receptors in ascites cells had a higher affinity for glucocorticoids than did receptors in subcutaneous cells, which indicated that sensitive and resistant cells contain chemically different classes of receptors. Loss of sensitivity occurred as tumors attained a diameter greater than approximately 1.5 cm. The reproducibility of this transition did not appear to be consistent with a random mechanism for loss of glucocorticoid sensitivity in vivo. Thus the acquisition of resistance by lymphosarcoma P1798 in vivo was concluded to be nonmutational and probably resulted from differentiational alteration in gene expression.
Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality
Authors: J.R. Ingram, P.N. Woo, S.L. Chua, A.D. Ormerod, N. Desai, A.C. Kai, K. Hood, T. Burton, F. Kerdel, S.E. Garner, V. Piguet
Journal: British Journal of Dermatology (2016)

More than 50 interventions have been used to treat hidradenitis suppurativa (HS), and so therapy decisions can be challenging. Our objective was to summarize and appraise randomized controlled trial (RCT) evidence for HS interventions in adults. Searches were conducted in Medline, Embase, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. The median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) by 4·0 points, which equates to the minimal clinically important difference for the scale, compared with placebo (95% confidence interval -6·5 to -1·5 points). Evidence quality was reduced to 'moderate' because the results are based on only a single study. Adalimumab 40 mg every other week was ineffective in a meta-analysis of two studies comprising 124 participants. Infliximab 5 mg kg(-1) improved the DLQI score by 8·4 points after 8 weeks in a moderate-quality study completed by 33 of 38 participants. Etanercept 50 mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions, including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate-quality evidence suggests that adalimumab given weekly and infliximab are effective, whereas adalimumab every other week is ineffective.
Effects of Tertiary Amine Local Anesthetics on the Blood-Borne Implantation and Cell Surface Properties of Metastatic Mouse Melanoma Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: G L Nicolson, I J Fidler, G Poste
Journal: JNCI Journal of the National Cancer Institute (1986)

Tertiary amine local anesthetics, such as dibucaine and tetracaine, have been found to reversibly modify the blood-borne implantation and experimental metastatic properties of B16 melanoma cells in syngeneic C57BL/6 mice. Local anesthetic treatment in vitro of low (B16-F1) and high (B16-F10) lung-colonizing melanoma variants reduced significantly their abilities to form lung tumor colonies, but the cells recovered their original in vivo colonizing properties within several hours after drug removal. Low drug concentrations (0.5 mM tetracaine) that altered the metastatic properties of these cells did not modify cell plating efficiencies or tumor growth rates at subcutaneous sites. With the use of [125]-5-iodo-2'-deoxyuridine-labeled B16 cells, the kinetic distributions of viable tumor cells in mice were also shown to be altered. Fewer cells were initially localized and retained in the lungs, and more cells reached extrapulmonary sites. Local anesthetics modified B16 cell morphology, inducing cell rounding and loss of microvilli. These effects occurred concomitant with alterations in microfilament organization. Anesthetic-treated cells also exhibited decreased cell-adhesion characteristics in both homotypic and heterotypic (endothelial and subendothelial matrix) cell-adhesion assays. Despite these changes, cell surface lactoperoxidase-catalyzed iodination of external proteins and labeling of cellular glycoproteins on polyacrylamide gels with 125I-labeled lectins did not reveal differences in the displays or quantities of cell surface glycoproteins after drug treatment. The data are consistent with the idea that reversible disruptions in transmembrane cytoskeletal control induced by local anesthetics result in alterations in cell shape, loss of stable adhesive interactions, and a decrease in blood-borne arrest and metastatic properties.
Pharmacogenetic influence of <i>OATP1B1</i> variants <i>*1b</i> and <i>*15</i> on irinotecan disposition in Asian and Caucasian cancer patients
Authors: B. Chowbay, A. Sparreboom, S. R Jada, X. Xiaoqiang, H. H Li, R. H Mathijssen, R. H van Schaik, J. Verweij, B. C. Goh, R. Lim, E. H Tan
Journal: Journal of Clinical Oncology (2006)

13069 Background: The objective of this study was to evaluate the impact of OATP1B1 (SLCO1B1; OATP-C) functional variants on the disposition of irinotecan in Asian and Caucasian cancer patients. Methods: Irinotecan pharmacokinetic parameters and OATP1B1*1a, *1b, *5 and *15 genotyping data were obtained from Asian (N=71) and Caucasian (N=30) cancer patients receiving the drug as a 90-minute i.v. infusion. Genotypic-phenotypic correlations were assessed in cancer patients from each ethnic group. Results: The *1a/*1a genotype and the *15/*15 diplotype were absent in Caucasian cancer patients but present in Asians (*1a/*1a, N=6; *15/*15, N=1). Statistically insignificant differences were observed between patients carrying *1a/*1b and *1b/*1b genotypes and also between *1b/*15, *15/*15 and *15/*15 diplotypes. Compared to wild-type patients (N=6), total irinotecan clearance normalized by BSA was 2- and 3-fold lower in Asian patients carrying at least one *1b (*1a/*1b + *1b/*1b; N=54; P=0.055) and one *15 (*1b/*15 + *5/*15 + *15/*15; N=11; P=0.001) allele, respectively. Significant differences were also present between Asian patients carrying the *15 diplotype and wild-type patients with regard to exposure levels (Cmax/dose/BSA) to irinotecan (P=0.007), SN-38 (P=0.009) and SN-38G (P=0.004) as well as REC (P=0.005) and REG (0.001). The REG was 5-fold (P=0.022) and 27-fold (P=0.001) lower in Asian cancer patients carrying at least one *1b allele and at least one *15 haplotype, respectively, when compared with wild-type patients. No significant differences in pharmacokinetic parameters were found when comparing Caucasian cancer patients carrying at least one *1b allele and those carrying at least one *15 allele (P&gt;0.05). Conclusions: The genotype and diplotype frequencies of the studied OATP1B1 variants were ethnically dependent, and OATP1B1 genotype status accounts, at least in part, for the observed differences in irinotecan disposition in Asian cancer patients. The lack of significant influence of OATP1B1 variants on irinotecan disposition in Caucasian cancer patients is not clear but may have resulted from the small patient population. No significant financial relationships to disclose.