tbuckley/cabot-search huggingface dataset:
Immunomodulation of responses to active immunization with a polyvalent immunotherapeutic: cyclophosphamide, H2 blockade, IL-2/IFNα and GM-CSF
Authors: M. B. Faries, E. C. Hsueh, R. K. Gupta, X. Ye, M. Hoban, R. Essner, L. J. Foshag, D. L. Morton
Journal: Journal of Clinical Oncology (2005)

2564 Background: Strong humoral and cellular immune responses in patients with melanoma receiving a specific active immunotherapeutic (Canvaxin; CancerVax Corp, Carlsbad, CA) have been correlated with improved survival. We examined the impact of several immunomodulators on the strength of immune response. Methods: Analysis of sequential phase II clinical trials using Canvaxin alone (n=446) or in combination with cyclophosphamide (n=92), cimetidine (n= 357), indomethacin (n=54) or IL-2/INFα (n=71) was performed with regard to maximal immune response within 16 weeks of treatment. A randomized clinical trial (n= 97) of Canvaxin with or without the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) was also analyzed. Delayed-type hypersensitivity (DTH) to vaccine was measured in all trials. IgM and IgG responses to the TA90 tumor-associated antigen were measured prospectively in the GM-CSF trial. Results: DTH responses were greater in patients with stage IV melanoma with concurrent cyclophosphamide (mean induration 20.6 mm with cyclophosphamide vs. 14.2 without, p=0.011). This was not seen in patients with stage III disease or in any stage with cimetidine, indomethacin or IL-2/IFNα treatment. The randomized GM-CSF trial did not show a significant difference (by logistic regression) in maximal DTH response (15.9± 9.7 mm with GM-CSF vs. 16.7 ± 9.9 mm without). There was a significant increase in maximal anti-TA90 IgM titers in the GM-CSF arm (797 ± 622 vs. 541 ± 533; p=0.0123), but no difference in anti-TA90 IgG (680 ± 557 with GM-CSF vs. 612 ± 510 without GM-CSF.) Maximal absolute lymphocyte counts during treatment were also elevated in the GM-CSF arm. Adverse event profiles were not markedly different, but GM-CSF patients reported more grade 1–2 fatigue. Conclusions: These data suggest that the addition of cyclophosphamide to adjuvant active specific immunotherapy in stage IV melanoma impacts DTH responses, and GM-CSF increases IgM response. Since this represents an impact on both the cellular (DTH) and humoral (IgM) arms of immunity, further study of modulator combinations is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CancerVax CancerVax
Improving medical education
Authors: P D Santos Ocampo
Journal: BMJ (2006)

Changes in the curricula of medical school training are needed to emphasize the role of oral rehydration therapy (ORT) in the management of acute diarrhea. In the Philippines, the Task Force on Pediatric Education has promoted a focus on such low-cost, highly effective health technologies in the competency-based pediatrics curriculum. The learning objectives emphasize practical skills and opportunities for hands-on experience. Teaching is conducted in the community, ambulatory care areas, wards, and ORT corners. Alternative teaching methods such as role playing, group discussions, and direct patient interaction are used to communicate to medical students the usefulness of ORT and the skills needed for its proper application. Deans and chairmen of the pediatric departments of all 26 medical schools in the Philippines have committed themselves to offering curricular programs on the management of diarrhea. Medical opposition to the use of ORT in diarrhea management, the major obstacle in the past, is expected to be diminished as a result of this effort.
Experiences with gastrointestinal stromal tumour at the Oncology Hospital Siglo XXI IMSS
Authors: F. Bustamante, E. Castillo, A. Silva, C. Martinez, L. Valenzuela
Journal: Journal of Clinical Oncology (2005)

9048 Background: The gastrointestinal stromal tumours (GIST) are neoplasm of the mesenchymal; their cells show similar characteristics to the interstitial cells of Cajal and are characterized by the expresion of CD117, the antigen to a specific transmembrane epitope of KIT; mutations of KIT have been demonstrated in more than 92% of GIST and this has a fundamental role in the development of this tumours. Imatinib mesylate is a type of tyrosine kinase inhibitor that selectively inhibits various tyrosine kinases including ABL, BCR/ABL, KIT and PDGF receptors. Methods: At the Oncology Hospital “Siglo XXI” seven patients were studied from January to September 2004 with a confirmed diagnostic by histopathology and immunohistochemical of stromal tumour. The patients were treated with Imatinib mesylate at dosis of 400 mg/per day. Results: With an average age of 59 years and with female sex predominance (6:1), the tumour was presented in the following areas: small intestine 2; rectum 2; gastric 1; mesenteric 1, papilla of Vater 1. From those, 4 were recurrent, 2 with metastatic disease and 1 with inoperable disease. With an average follow up of 9 months (5–10 months), from 7 patients, one had a complete response (14.28%) and two with partial response (28.57%), two with stable disease (28.57%) and with a overall response of 71.99% . Progression in two patients (28.57%). The treatment is well tolerated with gastrointestinal toxicity grade 1 for nausea. Conclusions: The imatinib mesylate achieved to induce objective responses in more than 50% of the patients with inoperable and/or metastatic disease, even though the follow up is still not long. Similar results are found in the literature. The KIT inhibition is a promising treatment with patients with GIST, whom are usually resistant to chemotherapy. No significant financial relationships to disclose.
Risk Factors for Hypocalcemia in Patients with Cancer Receiving Denosumab
Authors: J. Body, H.G. Bone, C. van Poznak, R.H. De Boer, A. Stopeck, R. Damião, K. Fizazi, D.H. Henry, T. Ibrahim, A. Lipton, F. Saad, N.D. Shore, T. Takano, H. Wang, O.L. Bracco, A. Balakumaran, P.J. Kostenuik
Journal: Annals of Oncology (2014)
Administration of pegfilgrastim on the same day or next day of chemotherapy
Authors: P. S. Hoffmann
Journal: Journal of Clinical Oncology (2005)

8137 Background: Though pegfilgrastim has reduced the number of injections compared with filgrastim, eliminating an office visit to receive pegfilgrastim on the day after chemotherapy is desirable. We have conducted a retrospective review of patient charts and electronic records to describe the safety of administering pegfilgrastim on the same day and the next day of chemotherapy. Methods: Data was collected for all patients receiving pegfilgrastim over a 10-week period at the Puget Sound Cancer Centers, a community-based oncology practice. Patients either received pegfilgrastim the day following chemotherapy (next-day) or the same day as chemotherapy. Data included tumor type, chemotherapy, hospital admission due to neutropenic fever, and minimum absolute neutrophil count (ANC) measured prior to the start of the next chemotherapy cycle or mid-cycle across all cycles of chemotherapy. Results: One hundred fifty-nine patient treatments, representing 15 tumor types and 50 chemotherapy regimens in various combinations, doses, and schedules, were reviewed. Seventy patient treatments received pegfilgrastim on the same day as chemotherapy and 89 patient treatments received pegfilgrastim on the day following chemotherapy. The distribution of tumor types was similar for the same-day and next-day patient groups. The proportion of patients with subsequent cycle prechemotherapy ANC< or = 1.5x109/L was 9% and 15% for patients receiving same-day and next-day pegfilgrastim, respectively. There was one hospital admission for neutropenic fever in the same-day pegfilgrastim group and 2 admissions for next-day administration group. Both patient groups experienced adverse events that would be expected for cancer patients receiving myelosuppressive chemotherapy. Conclusions: Patients receiving same-day pegfilgrastim generally experienced adequate ANC recovery to receive subsequent chemotherapy cycles. No unexpected adverse outcomes occurred. In our community practice, same-day administration of pegfilgrastim and chemotherapy was safe, benefiting patients and health-care providers, which might reduce costs. No significant financial relationships to disclose.
Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome
Authors: P. Khoury, R. Desmond, A. Pabon, N. Holland-Thomas, J. M. Ware, D. C. Arthur, R. Kurlander, M. P. Fay, I. Maric, A. D. Klion
Journal: Allergy (2016)

With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES).
Palliative chemotherapy of non-small cell lung cancer (NSCLC): Baseline data analysis of the ACTION observational study in 5 European countries
Authors: H. Bischoff, H. Anderson, H. Riska, S. Knowles, B. van den Borne, S. Bhalla, M. Hamann, M. Leschinger
Journal: Journal of Clinical Oncology (2005)

7216 Background: ACTION (Assessment of Cost and ouTcomes of chemotherapy In an Observational setting in patients with advanced NSCLC) is an on-going observational study in routine clinical practice. Methods: Between 4/2003 and 6/2004, 993 patients (pts) were recruited; 967 were evaluable, in Germany (D,571), UK (193), Finland (F,99), Netherlands (NL,69), and Portugal (P,35). Pts were ≥18 years old and receiving first-line chemotherapy for stage IIIB/IV NSCLC. Chemotherapy regimen was at discretion of the treating physician. Baseline data were collected on pt characteristics, diagnostic tests/pre-treatment interventions within 4 weeks of enrollment, and reasons for chemotherapy choice. Results: Median pt age was 64 years (range 31–90); 71% were male. WHO performance status was 0 in 21%, 1 in 65%, 2 in 10%, and 3/4 in 4%. There were inter-country differences in percent of pts with >10% weight loss (range F19%-P41%; mean 35%), and in percent with IIIB disease (range D27%-UK55%; mean 35%). Median times from current diagnosis ranged in days from D14 to UK28. Pre-chemotherapy staging investigations also showed regional differences: bronchoscopy (D87%, UK51%); bone scan (D72%, F11%); ultrasound (D91%, UK10%); and CT (D96%, UK67%). Third generation agents (gemcitabine, taxanes, vinorelbine) were used in 859 pts. Platinum was used in combination with a third generation agent in 693 pts: carboplatin 490 pts or cisplatin 203 pts. Efficacy of regimen was most common factor influencing treatment choice, Conclusions: Almost 1000 pts were recruited into this observational study within 15 months. There were inter-country variations in patient characteristics and in staging investigations prior to enrollment (possibly reflecting staging practice or system capacity). Most patients received third generation agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Amgen, AstraZeneca, GlaxoSmithKline, Lilly Oncology, Pierre Fabre Eli Lilly
Abstract 12316: Extracorporeal Cardiopulmonary Resuscitation With Cardiac Arrest Bypass System for Refractory Out-of-Hospital Cardiac Arrest is associated With Favorable Survival
Authors: Katsunori Mochizuki, Hiroshi Imamura
Journal: Circulation (2014)

Introduction: In a rural region with few medical resources, we have promoted the strategy that, if a refractory out-of-hospital cardiac arrest (OHCA) patient is likely reversible, the patient shoul...
Preventing the Preventable—Improving thromboprophylaxis in oncology in-patients
Authors: R. Stevens, R. Jones, S. Oliveras, T. Abdullah, R. Leonard
Journal: Journal of Clinical Oncology (2007)

19648 Background: Cancer and its treatments are well recognised risk factors for venous thromboembolism (VTE). The risk of VTE complications in malignancy can be increased with surgery, chemotherapy (including adjuvant chemotherapy), hormone therapy and central indwelling catheters. Low molecular weight heparin (LMWH) has been shown to safely reduce the incidence of VTE in cancer patients however it is often not a standard of care within the oncology in-patient setting. Method: A retrospective study was carried out on admissions to the oncology ward for 1 month. Individual VTE risk was assessed using the modified THRiFT II risk assessment model and it was documented whether patients received any form of prophylaxis and the incidence of VTE. Following this study a VTE prophylaxis protocol was designed and implemented on the oncology ward and a repeat prospective study was carried out. Results: The initial study showed that in the very high risk group only 15% patients received thromboprophylaxis. 4 episodes of VTE occurred during the initial study period and these all occurred in patients stratified as very high risk. On the repeat study the results showed 50% of patients assessed as very high risk were now receiving prophylaxis. There was also a reduction in the rate of inappropriate prophylaxis from 17% to 0% in those assessed as lower risk. Conclusion: Primary prevention of VTE helps to reduce the morbidity and mortality associated with this common complication of malignancy. This study shows how a simple risk assessment model coupled with raised awareness of VTE risk improved the prophylaxis of those at highest risk and also reduced inappropriate usage in those at lesser risk. No significant financial relationships to disclose.
Abstract 16043: The Role of eNOS Signaling in Wound Healing in a Murine Model of Diet-Induced Obesity
Authors: Petra Haberzettl, James McCracken, Bradford G Hill, Aruni Bhatnagar, Daniel J Conklin
Journal: Circulation (2014)

Background and Rationale: Type 2-diabetes is associated with the depletion of circulating endothelial progenitor cells (EPCs) and deficits in wound healing; conditions that have been linked to decreased activity of endothelial nitric oxide synthase (eNOS). However, it is not clear how, in the context of insulin resistance, increasing eNOS would affect EPC levels and wound healing. Therefore, we measured EPC levels and recovery from hind-limb ischemia (HLI) in wild-type and eNOS-transgenic (Tg) mice in a model of diet-induced obesity. Methods and Results: Wild-type (WT) C57BL/6 and eNOS-Tg mice were placed on a low (LFD) or high fat diet (HFD). After 12 weeks, the mice were subjected to HLI, and tissue perfusion was assessed by Laser Doppler Imaging. Levels of EPCs (Flk-1+/Sca-1+-cells) were measured by flow cytometry. HFD feeding, for 4-12 weeks, decreased circulating EPC levels while the levels of EPCs in the bone marrow were increased. Insulin (100 nM; 15 min) stimulated Akt and eNOS phosphorylation in aorta of LFD, but not HFD-fed mice, indicating insulin resistance. HFD decreased plasma NOx levels and activated the pro-inflammatory NF-κBα pathway in aorta, heart, liver, skeletal muscle and adipose tissue as analyzed by Western blot analysis. Recovery of blood perfusion, 2 weeks after HLI, was significantly higher in LFD than HFD-fed mice (76±3% vs. 21±4%; p&lt;0.05, n=5). Overexpression of eNOS prevented HFD-induced vascular insulin resistance, and enhanced recovery from HLI in both LFD (+64±4%) and HFD (+17±7%) fed mice. HLI decreased circulating EPC levels by about 30% in WT mice, while no changes in EPC levels were found in eNOS-Tg mice. Bone marrow EPCs were reduced after HLI in eNOS-Tg (28±8% of sham), but not in WT (94±27% of sham), mice. Conclusions: HFD impairs recovery from HLI, which may be related in part to vascular insulin resistance and decreased EPC mobilization. Deficits in the wound healing response due to diet-induced obesity could be overcome by increasing NO production via eNOS. Treatment strategies to increase NO bioavailability could promote wound healing in diabetic patients and prevent diabetic complications such as critical limb ischemia.
Addition of continuous low dose temozolomide (T) to bevacizumab (Bev) plus irinotecan (Iri) after bevacizumab plus irinotecan failure in heavily pretreated glioblastoma multiforme (GBM)
Authors: S. Stankewitz, G. Dresemann
Journal: Journal of Clinical Oncology (2009)

e13015 Background: In several phase II studies in relapsed GBM, Bev plus Iri showed impressive objective response rates (&gt;50%) with acceptable toxicity rate, duration of response, however, was moderate. Methods: From April 2007 to October 2008, 35 pretreated patients with confirmed GBM with progressive disease (PD) after Bev (4 mg/kg body weight i.v.) plus Iri (80 mg/m 2 i.v.) were treated with additional continuous low dose T (20 mg per day p.o.) while Bev plus Iri were continued. ECOG performance status (PF) was 0 - 2 in all pts. MRI scan was required after 4 weeks and every 6 weeks afterwards. MacDonald criteria were used for evaluation of response. If MRI scans could not be performed, patients were considered to have PD. Treatment was given until PD or intolerable toxicity occurred. Results: All 35 patients were eligible for toxicity and efficacy, median follow up was 7 months (2 - 20), 25 patients were male, 10 female, median age was 51 years (29 - 80), 21 patients had primary GBM, 14 patients secondary GBM. All patients had prior irradiation (56 - 60 Gy) 2 patients had 5, 8 patients had 4, 15 patients had 3, and 10 patients 2 prior chemotherapeutic regimen. 1 patient developed grade 3 leucopenia, and 1 patients grade 3 thrombopenia; 3 patients asymptomatic intracerebral bleeds requiring treatment delay, 1 pat. grade 3 sepsis and 2 patients grade 3 fatigue. In 4/35 patients a partial response (PR) was achieved, in 14/35 patients a disease stabilization for at least 2 months, while 17/35 patients showed primary PD. Median duration of PR was 3.5 months (2–5), median duration of SD was 5 months (2–13), Median survival was 5 months (2–13). Data will be updated. Conclusions: The addition of continuous low dose T in combination with Bev plus Iri seems to have activity in GBM patients, after progression on Bev plus Iri treatment, and has an acceptable toxicity profile. Further investigation of the combination Bev plus Iri plus T in GBM patients is necessary. No significant financial relationships to disclose.
Recent evolutionary history of American Onchocerca volvulus, based on analysis of a tandemly repeated DNA sequence family.
Authors: P A Zimmerman, C R Katholi, M C Wooten, N Lang-Unnasch, T R Unnasch
Journal: Molecular Biology and Evolution (1994)

Polymerase chain reaction (PCR) products were characterized for a repeated sequence family (designated "O-150") of the human filarial parasite Onchocerca volvulus. In phylogenetic inferences, the O-150 sequences clustered into closely related groups, suggesting that concerted evolution maintains sequence homology in this family. Using a novel mathematical model based on a nested application of an analysis of variance, we demonstrated that African rainforest and savannah strain parasite populations are significantly different. In contrast, parasites collected in the New World are indistinguishable from African savannah strains of O. volvulus. This finding supports the hypothesis that onchocerciasis was recently introduced into the New World, possibly as a result of the slave trade.
Three facets of the study need attention
Authors: K. Prasad, M. Malik, B. Mendzelevski
Journal: BMJ (1996)

Single dose of oral dexamethasone for outpatient croupFailure to follow up all patients is a concern EDrTOR,-G C Geelhoed and colleagues con- clude from their study that oral dexamethasone at a dose of 0.15 mg/kg is effective in reducing return to medical care in children with mild croup.'The sample size seems adequate, though on the borderline for detecting a 90% reduction, but the fact that four children were not followed up is of concern.If the two children lost to follow up in the treatment group had in fact sought some medical care (or even died) this would have meant that the difference in outcome between the two groups was not significant by Fisher's exact test.We wonder why the calculation of sample size assumed such a large reduction as 90%.Was this a retrospective calculation?The final key message states that all children presenting with croup should be considered for steroids.Before the authors' findings can be generalised we need to know what proportion of children who presented with mild croup were excluded from the trial and what the rate of parental refusal was.
Cathepsin D in Podocytes Is Important in the Pathogenesis of Proteinuria and CKD
Authors: Kanae Yamamoto-Nonaka, Masato Koike, Katsuhiko Asanuma, Miyuki Takagi, Juan Alejandro Oliva Trejo, Takuto Seki, Teruo Hidaka, Koichiro Ichimura, Tatsuo Sakai, Norihiro Tada, Takashi Ueno, Yasuo Uchiyama, Yasuhiko Tomino
Journal: Journal of the American Society of Nephrology (2016)

Studies have revealed many analogies between podocytes and neurons, and these analogies may be key to elucidating the pathogenesis of podocyte injury. Cathepsin D (CD) is a representative aspartic proteinase in lysosomes. Central nervous system neurons in CD-deficient mice exhibit a form of lysosomal storage disease with a phenotype resembling neuronal ceroid lipofuscinoses. In the kidney, the role of CD in podocytes has not been fully explored. Herein, we generated podocyte–specific CD–knockout mice that developed proteinuria at 5 months of age and ESRD by 20–22 months of age. Immunohistochemical analysis of these mice showed apoptotic podocyte death followed by proteinuria and glomerulosclerosis with aging. Using electron microscopy, we identified, in podocytes, granular osmiophilic deposits (GRODs), autophagosome/autolysosome-like bodies, and fingerprint profiles, typical hallmarks of CD-deficient neurons. CD deficiency in podocytes also led to the cessation of autolysosomal degradation and accumulation of proteins indicative of autophagy impairment and the mitochondrial ATP synthase subunit c accumulation in the GRODs, again similar to changes reported in CD-deficient neurons. Furthermore, both podocin and nephrin, two essential components of the slit diaphragm, translocated to Rab7– and lysosome–associated membrane glycoprotein 1–positive amphisomes/autolysosomes that accumulated in podocyte cell bodies in podocyte–specific CD–knockout mice. We hypothesize that defective lysosomal activity resulting in foot process effacement caused this accumulation of podocin and nephrin. Overall, our results suggest that loss of CD in podocytes causes autophagy impairment, triggering the accumulation of toxic subunit c–positive lipofuscins as well as slit diaphragm proteins followed by apoptotic cell death.