tbuckley/cabot-search huggingface dataset:
Citrullination of Epithelial Neutrophil–Activating Peptide 78/CXCL5 Results in Conversion From a Non–Monocyte‐Recruiting Chemokine to a Monocyte‐Recruiting Chemokine
Authors: Ken Yoshida, Olexandr Korchynskyi, Paul P. Tak, Takeo Isozaki, Jeffrey H. Ruth, Phillip L. Campbell, Dominique L. Baeten, Danielle M. Gerlag, M. Asif Amin, Alisa E. Koch
Journal: Arthritis & Rheumatology (2014)

Objective To examine whether the citrullinated chemokines epithelial neutrophil–activating peptide 78 (ENA‐78)/CXCL5, macrophage inflammatory protein 1α/CCL3, and monocyte chemotactic protein 1/CCL2 are detected in the biologic fluid of patients with rheumatoid arthritis (RA), and if so, to determine the biologic activities of these chemokines. Methods Recombinant human chemokines were citrullinated by peptidylarginine deiminase. Enzyme‐linked immunosorbent assays were performed to measure the concentrations of citrullinated chemokines in sera from patients with rheumatoid arthritis (RA) and normal individuals and in synovial fluid from patients with RA, patients with osteoarthritis (OA), and patients with other inflammatory rheumatic diseases. The correlation between the citrullinated chemokine levels and clinical data was analyzed. Monocyte and neutrophil chemotaxis assays were performed, and native (noncitrullinated) or citrullinated ENA‐78/CXCL5 was injected into mouse knees to evaluate the biologic activities of these chemokines. Results The concentration of citrullinated ENA‐78/CXCL5 was significantly higher in RA sera and SF than in normal sera and in SF from patients with other rheumatic diseases including OA. In RA SF, a strong correlation between the amount of citrullinated ENA‐78/CXCL5 and the C‐reactive protein level or the erythrocyte sedimentation rate was observed. Citrullinated ENA‐78/CXCL5 induced monocyte chemotaxis via CXCR1 and CXCR2, while noncitrullinated ENA‐78/CXCL5 did not. In a mouse model of inflammatory arthritis, citrullinated ENA‐78/CXCL5 induced more severe inflammation and recruited more monocytes than did noncitrullinated ENA‐78/CXCL5. Conclusion Citrullinated ENA‐78/CXCL5 is highly correlated with RA disease activity and, unlike noncitrullinated ENA‐78/CXCL5, recruits monocytes. These results indicate that citrullinated ENA‐78/CXCL5 may exert previously unrecognized inflammatory properties in RA by recruiting monocytes to inflamed joint tissue.
Changes in the clearance of total and unbound etoposide in patients with liver dysfunction.
Authors: C F Stewart, S G Arbuck, R A Fleming, W E Evans
Journal: Journal of Clinical Oncology (1990)

The disposition of total and non-protein-bound etoposide was investigated in 21 cancer patients receiving etoposide and cisplatin combination chemotherapy. Etoposide plasma concentrations were determined using a specific high-performance liquid chromatography (HPLC) method, and etoposide plasma protein binding was determined by equilibrium dialysis. The patients had a wide range of renal function (creatinine clearance, 32 to 159 mL/min/m2) and hepatic function (total bilirubin range, 0.3 to 21.5 mg/dL; aspartate aminotransferase [AST] range, 14 to 415 IU/L; serum albumin range, 2.7 to 4.1 g/dL). The mean etoposide total systemic clearance was not different in 15 patients with total bilirubin less than 1.0 mg/dL versus six patients with total bilirubin 1.1 to 21.5 mg/dL (18.7 +/- 5.9 mL/min/m2 v 26.4 +/- 10.7 mL/min/m2; t-test P = .06), with a trend toward higher total clearance in the patients with abnormal bilirubin values. However, the mean clearance of unbound etoposide was significantly lower in patients with increased total bilirubin (220 +/- 90 mL/min/m2 v 135 +/- 61 mL/min/m2; t-test P = .027). The fraction of etoposide unbound (fu) in plasma was significantly higher in patients with increased bilirubin (9% +/- 3% v 27% +/- 15%; t-test P = .002), explaining the trend toward higher total clearance in these patients. Etoposide clearance (total or unbound) in the 14 patients with measurable hepatic metastases was not different from the clearance in the seven patients without hepatic metastases. This study provides an explanation for why patients with increased bilirubin do not have lower total systemic clearance of etoposide, and indicates that such patients have a higher exposure to unbound etoposide. The results of ongoing pharmacodynamic studies of total and unbound etoposide in patients with increased bilirubin will determine the clinical relevance of altered etoposide protein binding.
Treatment of hemoptysis in inoperable patients with pulmonary aspergilloma: Value of percutaneous instillation of fluconazole
Authors: Youngchun Ko, Jongpil Jung, Chanwoo Park
Journal: European Respiratory Journal (2013)

OBJECTIVE Surgery has been the primary choice of treatment for cavitary aspergillomas of the lung, but it is associated with relatively high morbidity and mortality. Percutaneous intracavitary instillation of amphotericin B is a safe and effective method of treating hemoptysis caused by aspergillomas in inoperable patients. Aspergillus  terreus  are frequent resistant to Amphotericin B. So that the newer azoles maybe the drug of choice. The effectiveness of percutaneous instillation of an antifungal agent in seven patients with hemoptysis caused by pulmonary aspergilloma was evaluated.  SUBJECTS AND METHODS All patients had hemoptysis associated with pulmonary aspergilloma. 50 mg fluconazole of in 20 ml of 5% dextrose in water were instilled into the cavity through a 23-gauge needle. The presence or absence of hemoptysis was recorded after each instillation of fluconazole, and the size of aspergilloma was assessed with follow-up radiographs.  RESULTS Hemoptysis ceased within 5 days after instillation of fluconazole in all patients. In the six patients treated through a fine needle, the aspergillomas resolved partially. Mild hemoptysis during the procedure, a small pneumothorax occurred in one patient each.  CONCLUSION. Our results suggest that or it presented the possibility of effective treatment method in inoperable patients with massive hemoptysis or repetitive hemoptysis.
High prevalence of asthma and related symptoms in teenagers in northern Sweden
Authors: E Norrman, L Rosenhall, L Nyström, E Bergstrm, N Stjenberg
Journal: European Respiratory Journal (1993)

Recent reports have suggested an increased asthma prevalence in the Nordic countries. The prevalence of asthma and related symptoms from lower airways in Umeå, Northern Sweden, was investigated in 1987. We used a questionnaire and a skin prick test in 1,112 teenagers. Individuals with symptoms or positive skin prick tests were examined further. The clinical examination included an interview, a ventilatory lung function test, serum specific immunoglobulin E (IgE) test, and a physical examination. Individuals with symptoms from the lower airways underwent a methacholine inhalation test. Asthma was defined as recurrent attacks of dyspnoea and/or wheezing, triggered by known stimuli (excluding infections), and at least one of the following: signs of obstructive airways at examination or provocation concentration giving a 20% fall in forced expiratory volume in one second (PC20) < 8 mg.ml-1. Using this definition, the prevalence of asthma was 6.8%, with a significantly higher prevalence in girls (9.6%) than in boys (4.1%). Furthermore, 16.4% had dyspnoea, wheeze or prolonged cough but did not fulfil our criteria for asthma. The prevalence of asthma and of symptoms from lower airways is higher than has previously been found in Sweden.
Oct1 and OCA-B are selectively required for CD4 memory T cell function
Authors: Arvind Shakya, Alon Goren, Alex Shalek, Cody N. German, Jeremy Snook, Vijay K. Kuchroo, Nir Yosef, Raymond C. Chan, Aviv Regev, Matthew A. Williams, Dean Tantin
Journal: The Journal of Experimental Medicine (2015)

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4+ memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4+ T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4+ T cell memory.
Contribution of positive renal vein margin to relapse risk in renal cell cancer
Authors: J. J. McFarlane, A. Liman, M. Jahanzeb
Journal: Journal of Clinical Oncology (2008)

16110 Background: Positive margins in surgically resected solid tumors usually connote higher local relapse rate. There is some evidence this may not be so in renal cell cancer (RCC), and the significance of involvement of the renal vein margin (RVM) is especially difficult to interpret. We reviewed tumor registry data to assess the relapse rate in such scenarios. Methods: After IRB approval, the tumor registry of the Memphis VA hospital was queried for patients with RCC, stage T3b/ T3c, N(any), M0 treated by nephrectomy. Charts were reviewed for known prognostic variables including TNM stage, Fuhrman grade, and involvement of the adrenal gland or perinephric fat. Margin status was assessed, with RVM involvement distinguished from other margins. Outcomes recorded were site and date of recurrence, and date of last contact or death. Local recurrence (LR) and distant recurrence (DR) rates and mean time to recurrence (TTR) were calculated according to RVM status. Survival and TTR were calculated from date of nephrectomy. Results: Of 313 kidney cancer patients, 16 met the above criteria. Mean follow-up was 3.7 years. Two patients had no follow up. No patients had LR. Four died after DR (mean survival 1.3 yr); 5 died without relapse (mean survival 5.1 yrs); 4 are alive without relapse (mean followup 7.7 yrs) and 1 is alive with disease after 7 yrs. Three patients with positive RVM all had DR with mean TTR 2.96 years (range 0.05 to 6.34); two have died (survivals 3 and 0.2 yrs) while the other is alive at 7 yrs. Of the other 11 patients with adequate followup, 3 (27%) had DR with mean TTR 1.0 years (range 0.47 to 1.48); two died at 1 yr, one was lost to follow up after 2 yrs. One patient with a positive ureter margin was lost to follow up. No patients underwent adjuvant treatment. Conclusions: Our data are consistent with the previous evidence that positive margins in RCC may not connote a high rate of local relapse. However, positive RVM was associated with a high rate of distant recurrence. This indicates a need to include such patients in clinical trials of newly emerging systemic therapies instead of focusing on delivery of local therapy. No significant financial relationships to disclose.
Clearance systems in the brain—implications for Alzheimer disease
Authors: Jenna M. Tarasoff-Conway, Roxana O. Carare, Ricardo S. Osorio, Lidia Glodzik, Tracy Butler, Els Fieremans, Leon Axel, Henry Rusinek, Charles Nicholson, Berislav V. Zlokovic, Blas Frangione, Kaj Blennow, Joël Ménard, Henrik Zetterberg, Thomas Wisniewski, Mony J. de Leon
Journal: Nature Reviews Neurology (2015)
Malignant transformation of teratoma to primitive neuroectodermal tumor (PNET): Outcome analysis with PNET based chemotherapy
Authors: M. Brames, Y. Ehrlich, L. Einhorn
Journal: Journal of Clinical Oncology (2009)

e16121 Background: Metastatic testis cancer is uniquely chemosensitive and highly curable. Residual teratoma can be surgically resected. However, testicular teratoma can differentiate along endodermal, ectodermal, or mesodermal elements (malignant transformation of teratoma), with capacity to metastasize and not be amenable to surgical resection. We report results of malignant transformation of teratoma to metastatic PNET treated with PNET based chemotherapy. Methods: Retrospective review of 42 patients with PNET in testis or at metastatic sites seen at Indiana University from 1999–2007. Of these 42 patients, 10 had inoperable or unresectable PNET treated with cyclophosphamide 1200 mg/M 2 , doxorubicin 75 mg/M 2 , and vincristine 2 mg IV alternating with ifosfamide 1.8 grams/M 2 × 5 days plus etoposide 100 mg/M 2 × 5 days. Courses were given every 3 weeks for 6 courses or until progression or undue toxicity. Results: 9 of 10 patients had at least 1 prior platinum based combination chemotherapy regimen for their germ cell tumor. Tumor markers (human chorionic gonadotropin and alphafetoprotein) were normal at start of chemotherapy for biopsy proven PNET. Eight of 10 achieved objective response. Two of 10 are currently disease-free for 16 and 33 months from initiation of PNET specific chemotherapy and 3 other patients are alive with disease at 73, 34, and 30 months. These 5 patients all had subsequent surgery. Conclusions: PNET specific chemotherapy has a high objective response rate for malignant transformation of teratoma to PNET, with some patients capable of long-term survival with chemotherapy followed by surgical resection. [Table: see text]
Thioridazine, Diarrhoea and Torsades De Pointe
Authors: M A Denvir, A Sood, R Dow, A J Brady, A C Rankin
Journal: Journal of the Royal Society of Medicine (1998)

and 7 years respectively6. On the rare occasions when very young children develop sinusitis, the disease tends to be mild; but serious complications can arise7-9 because of the close proximity of cranial structures. The orbit is the structure most commonly involved, with cellulitis; intracranial complications include meningeal irritation, meningitis and abscess. Once sinusitis has been diagnosed it must be aggressively treated with antibiotics7-10 directed against the most likely causal organisms. Acute and chronic sinusitis in children seem to be caused by different organisms, the pathogens causing acute sinusitis being similar in type to those causing acute otitis media6. A ten-day course of antibiotics is suitable to treat acute sinusitis6'7 but insufficient for chronic sinusitis, which takes three to four weeks to clear. Those cases unresponsive to medical therapy may require surgical intervention to correct any structural abnormalities predisposing to the sinusitis. With such potential complications, as well as the severe pain, medical practitioners should be on guard at all times to detect occult sinusitis in patients with atypical headache. REFERENCES
The follow-up of children with tracheobronchial foreign body aspiration
Authors: Sinan Tas, Zeynep Seda Uyan, Nihal Uyar, Yonca Anik, Tuba Liman, Metin Aydogan, Salih Topcu, Emin Sami Arisoy
Journal: European Respiratory Journal (2011)

Background:  Foreign body aspiration (FBA) is an important cause of morbidity and mortality in children   Objectives:  Retrospective analysis of cases who arrived Kocaeli Universtiy Hospital with suspected FBA and underwent bronchoscopy   Methods:  Forty children who underwent bronchoscopy for FB removal from February 2005 to January 2010 at Kocaeli Universtiy Hospital were reviewed retrospectively.We recorded the patients9 presenting symptoms,physical and radiological findings,the time elapsed from aspiration to presentation,type and location of FB,acute and long-term complications,follow up period and hospitalisation period   Results:  There were 26 male patients.The mean age was 59,8±34,2 months (range 29-195 months).FBs were removed within 1-184 days following the aspiration (median: 2 days).During presentation;38 cases had clinical symptoms and wheezing was the most common one.Thirty-three FBs were organic and hazelnuts were the most common. Twenty-three (57.5%) cases had radiological findings during presentation and 10 (25%) had acute complications (pneumonia).Patients were hospitalized for 1-17 days (median 2days) and followed up for 34,5±31,3 months. Seventeen patients had persistent clinical symptoms.There were chronic radiological findings in 5 patients and fibrotic sequelaes in 11 patients.Although statistically not significant; chronic radiological findings were more common in patients in whom bronchoscopy was performed lately   Conclusions:  Follow up period and methods of chidren with tracheobrachial FBA are controversial. Additionally, there are not enough studies about its long term complications.Some patients cannot be followed up for a sufficient period and this can lead to the development of chronic changes.
Contaminants of PC-SPES are not responsible for cytotoxicity in human small-cell lung carcinoma cells
Authors: David Sadava
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

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PC-SPES is a mixture of herbs used in the treatment of prostate cancer. Batches of this product were found to contain traces of synthetic drugs, and the product was removed from the market. On the basis of a correlation between contaminant levels and cytotoxicity in prostate carcinoma cell lines, Sovak et al. (JNCI 17: 1275 (2002)) concluded that the contaminants were responsible for cytotoxicity of this preparation. We have shown that extracts of PC-SPES are cytotoxic and pro-apoptotic in both drug-sensitive (H69) and drug resistant (H69V) human small-cell lung carcinoma (SCLC) cell lines (Sadava et al., Cancer Chemo. Pharmacol. 49: 261 (2002)) and investigated whether the contaminants might be responsible for these effects. In contrast to the data reported for prostate carcinoma cells, extracts of lots of PC-SPES from 1998 (reportedly contaminated) and 2001 (much less contaminated) were equally cytotoxic in both SCLC cell lines. Tests of individual contaminants gave IC50 values far in excess of the amounts reported to be present in the IC50 level for the PC-SPES extracts: Diethlystilbesterol: actual IC50 in H69 cells, > 1000 uM; concentration present in herbal extract at IC50, 0.05-0.2 uM; indomethacin: actual IC50 in H69 cells, 800 uM; concentration in herbal extract, 1.5-20 uM; warfarin: actual IC50 in H69 cells, 950 uM; concentration in herbal extract, 0.57-0.93 uM. Adding the calculated maximum concentration of the contaminants, singly or in combination, to extracts of the later (2001) batch of PC-SPES did not alter the cytotoxicity of the extract in H69 or H69V cells. At the contaminated concentrations, as well as 5x those concentrations, none of the contaminants was pro-apoptotic, as indicated by a DNA fragmentation kinetics assay. However, extracts of both early and late batches of PC-SPES were pro-apoptotic in H69 and H69V cells. We conclude that the traces of pharmaceuticals found in PC-SPES were not responsible for its cytotoxic and pro-apoptotic activities on SCLC cells.
Intraoperative protective ventilation: too early to redefine management parameters?
Authors: Nahel Saied, Mohammad A Helwani, Pratik P Pandharipande
Journal: BMJ (2015)

The attention to detail, use of a large representative dataset, and rigorous statistical approach in Ladha and colleagues’ study of intraoperative mechanical ventilation and postoperative respiratory complications all help advance our knowledge.1 However, important limitations mean that these data must be interpreted with caution, especially before changing ventilatory management practices for patients in the operating room.

In a retrospective analysis of prospectively collected data, the authors showed in both unmatched and propensity matched analyses that patients who had all three of low plateau pressures (Pplat), low tidal …
Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer.
Authors: G A Masters, P C Hoffman, A Hsieh, L C Drinkard, R Mick, B L Samuels, A Guaspari, H M Golomb, E E Vokes
Journal: Journal of Clinical Oncology (1997)

PURPOSE We designed a phase I dose-escalation study of vinorelbine on a novel (daily-times-three) schedule with ifosfamide with granulocyte colony-stimulating factor (G-CSF) support to define the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of vinorelbine in this combination. PATIENTS AND METHODS Cohorts of patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) and no prior chemotherapy received vinorelbine starting at 15 mg/m2 on days 1, 2, and 3, and ifosfamide starting at 2.0 g/m2 on days 1, 2, and 3 with G-CSF support for all patients. Cycles were repeated every 21 days. Plasma vinorelbine concentrations were also analyzed. RESULTS Forty-two patients were treated. The median age was 58 years (range, 34 to 75) and 41 had a performance status of 0 or 1. The DLT was neutropenia and sepsis at a maximum-administered vinorelbine dose of 35 mg/m2 for 3 days. The recommended phase II dose was vinorelbine 30 mg/m2 with ifosfamide 1.6 g/m2 both given on 3 consecutive days. The overall response rate was 40% (17 of 42; all partial responders). The median survival duration was 50 weeks, with a 1-year survival rate of 48%. Pharmacokinetic analysis showed that vinorelbine in this combination and on this schedule is cleared 1.5 to two times faster than in single-agent once-weekly studies. CONCLUSION Myelosuppression is the DLT of this regimen with no major subjective toxicities. With tolerable toxicity and an encouraging 1-year survival rate of 48%, further investigation of this new vinorelbine schedule is warranted in this and other combination regimens.