tbuckley/cabot-search huggingface dataset:
Phase I trial of recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast in patients with breast cancer receiving cyclophosphamide, doxorubicin, and fluorouracil.
Authors: S E O'Reilly, K A Gelmon, N Onetto, J Parente, M Rubinger, R A Page, I H Plenderleith
Journal: Journal of Clinical Oncology (1993)

To establish the optimum biologic dose and maximal-tolerated dose (MTD) of once-daily, subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor derived from yeast (RhuGM-CSF) in patients with breast cancer.Seventeen patients with either newly diagnosed breast cancer with more than four involved axillary nodes (five patients) or metastatic breast cancer (12 patients) were treated with cyclophosphamide 1 g/m2, doxorubicin 50 mg/m2, and fluorouracil 500 mg/m2 (CAF) intravenously (IV) once every 3 weeks. RhuGM-CSF was administered subcutaneously once daily for 14 days after the second and third CAF cycles, at one of three dose levels.The 125-micrograms/m2/d RhuGM-CSF dose level shortened the duration of neutropenia in only one of three patients. The 250-micrograms/m2/d level was effective in shortening the duration of the neutropenic nadir (< .5 x 10(9)/dL) by 2 or more days in five of six patients. The 500-micrograms/m2/d level caused severe toxicity (chest pain, two patients; deep vein thrombosis, one patient) in three of eight patients.RhuGM-CSF administered once daily at the 250-micrograms/m2/d level is well tolerated and effective in shortening the duration of the neutrophil nadir by 2 or more days after CAF therapy.
Labeling Index as a Prognostic Marker in Non-Hodgkin's Lymphomas&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;
Authors: Aurora Costa, Gianni Bonadonna, Eugenio Villa, Pinuccia Valagussa, Rosella Silvestrini
Journal: JNCI Journal of the National Cancer Institute (1981)

The labeling index (LI) was determined at the time of initial diagnosis of 88 untreated adults with non-Hodgkin's lymphomas. The frequency distribution of low (≤4%) and high (>4%) LI between tumors with nodular and diffuse histologic patterns was significantly different (P<O.001): The median LI was about four times greater for diffuse lymphomas than for nodular lymphomas. LI was not correlated with either disease extent or systemic symptoms. In patients with tumors of low LI, complete remission occurred in 86% of those with nodular lymphomas and in 74% of those with diffuse lymphomas. These values were significantly different from the 17 and 39% observed respectively for nodular and diffuse lymphomas with high LI. Patients with low LI had greater actuarial 4-year survival than did those with high LI (P<10-7). Highly significant differences between the two kinetic groups were also observed within nodular and diffuse patterns. However, whereas the difference for nodular lymphomas was independent of histologic subtype and stage, this was not always true for all subtypes of diffuse lymphomas. LI could be a useful marker to identify prior to treatment the patients who could enter complete remission and have favorable survival. Its clinical relevance as a prognostic factor appeared superior to the Rappaport histologic classification and pathologic stage, especially in patients with nodular histology.
Intrauterine Exposure to Environmental Pollutants and Body Mass Index during the First 3 Years of Life
Authors: Stijn L. Verhulst, Vera Nelen, Elly Den Hond, Gudrun Koppen, Caroline Beunckens, Carl Vael, Greet Schoeters, Kristine Desager
Journal: Environmental Health Perspectives (2008)

We investigated the association between body mass index (BMI) standard deviation score (SDS) and prenatal exposure to hexachlorobenzene, dichlorodiphenyldichloroethylene (DDE), dioxin-like compounds, and polychlorinated biphenyls (PCBs).
Study of pleural empyema evolution depending on drainage size used
Authors: Sonia Herrero, Amaia Atenea Iridoy, Vanessa López, Maria Isabel Andrade, Pilar Cebollero, Idoia Pascal
Journal: European Respiratory Journal (2013)

Objective: Pleural drainage (PD) is the initial treatment option in patients with empyema. The aim of our study was to analyze the evolution of the empyema treated with PD depending on tube size used.  Material and Methods: This is a retrospective study over 10 years. We have analyzed the type of PD used (small (≤ 14F) and large (> 14F)), days of hospitalization (DH), fluid biochemical data, thoracic ultrasound, use of fibrinolysis, need for decortication and mortality. Placing either PD size is done randomly without following any clinical or biochemical criteria.  Results: We reviewed 50 patients, 72% were men and the average age was 53.14 ± 14.7 years. Small tube was placed in 40%, large tube in 48% and unknown thickness in 12%. The average pH of pleural fluid was 6.74 ± 0.43. The days until the placement of the DP were 3.58 ± 4.37. The average hospital stay was 21.04 ± 12.12 days. In a 36% thoracic ultrasound was made with a delay of 0.26 ± 0.45 days from request. In a 63.27% fibrinolysis was used. Total mortality was 4% with good evolution of the remaining patients, of whom 6% needed decortication.  We used a Chi-square to assess mortality and surgery needs depending on tube size and t-Student to analyze the DH depending on tube size (table1) and the delay in the placement of PD (table2).  Conclusions:  • In our practice, small drainage is as effective as the large tube for the treatment of pleural empyema.  • An excessive delay in the placement of pleural drainage is associated with an increase in hospitalization days.
Congenital Transmission of Murine Leukemia Virus From Wild Mice Prone to the Development of Lymphoma and Paralysis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: M B Gardner, A Chiri, M F Dougherty, J Casagrande, J D Estes
Journal: JNCI Journal of the National Cancer Institute (1979)

Maternal congenital transmission of infectious murine leukemia virus, primarily via milk, was the major route of virus spread in Lake Casitas (LC) wild mice and in crosses of LC mice with uninfected wild and laboratory mice. An indirect extrachromosomal male transmission in utero of LC virus also readily occurred in matings of viremic LC males with C57L females but apparently not with other uninfected wild or NIH Swiss females. Both amphotropic and ecotropic classes of LC murine leukemia viruses were potentially transmissible by congenital and venereal epigenetic means and could induce the same two diseases, lymphoma and paralysis, that occurred naturally in LC wild mice. Lymphoma and paralysis both failed to occur in uninfected LC mice or their hybrid progeny that escaped congenital infection.
Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports
Authors: Jennita Reefhuis, Owen Devine, Jan M Friedman, Carol Louik, Margaret A Honein
Journal: BMJ (2015)

<b>Objective</b> To follow up on previously reported associations between periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and specific birth defects using an expanded dataset from the National Birth Defects Prevention Study. <b>Design</b> Bayesian analysis combining results from independent published analyses with data from a multicenter population based case-control study of birth defects. <b>Setting</b> 10 centers in the United States. <b>Participants</b> 17 952 mothers of infants with birth defects and 9857 mothers of infants without birth defects, identified through birth certificates or birth hospitals, with estimated dates of delivery between 1997 and 2009. <b>Exposures</b> Citalopram, escitalopram, fluoxetine, paroxetine, or sertraline use in the month before through the third month of pregnancy. Posterior odds ratio estimates were adjusted to account for maternal race/ethnicity, education, smoking, and prepregnancy obesity. <b>Main outcome measure</b> 14 birth defects categories that had associations with SSRIs reported in the literature. <b>Results</b> Sertraline was the most commonly reported SSRI, but none of the five previously reported birth defects associations with sertraline was confirmed. For nine previously reported associations between maternal SSRI use and birth defect in infants, findings were consistent with no association. High posterior odds ratios excluding the null value were observed for five birth defects with paroxetine (anencephaly 3.2, 95% credible interval 1.6 to 6.2; atrial septal defects 1.8, 1.1 to 3.0; right ventricular outflow tract obstruction defects 2.4, 1.4 to 3.9; gastroschisis 2.5, 1.2 to 4.8; and omphalocele 3.5, 1.3 to 8.0) and for two defects with fluoxetine (right ventricular outflow tract obstruction defects 2.0, 1.4 to 3.1 and craniosynostosis 1.9, 1.1 to 3.0). <b>Conclusions</b> These data provide reassuring evidence for some SSRIs but suggest that some birth defects occur 2-3.5 times more frequently among the infants of women treated with paroxetine or fluoxetine early in pregnancy.
Case–control comparison of bacterial and protozoan microorganisms associated with gastroenteritis: application of molecular detection
Authors: L E S Bruijnesteijn van Coppenraet, M Dullaert-de Boer, G J H M Ruijs, W A van der Reijden, A G M van der Zanden, J F L Weel, T A Schuurs
Journal: Clinical Microbiology and Infection (2015)

The introduction of molecular detection of infectious organisms has led to increased numbers of positive findings, as observed for pathogens causing gastroenteritis (GE). However, because little is known about the prevalence of these pathogens in the healthy asymptomatic population, the clinical value of these additional findings is unclear. A case-control study was carried out in a population of patients served by general practitioners in the Netherlands. A total of 2710 fecal samples from case and matched control subjects were subjected to multiplex real-time PCR for the 11 most common bacterial and four protozoal causes of GE. Of 1515 case samples, 818 (54%) were positive for one or more target organisms. A total of 49% of the controls were positive. Higher positivity rates in cases compared to controls were observed for Campylobacter spp., Salmonella spp., Clostridium difficile, enteroinvasive Escherichia coli/Shigella spp., enterotoxigenic E. coli, enteroaggregative E. coli, atypical enteropathogenic E. coli (EPEC), Cryptosporidium parvum/hominis, and Giardia lamblia. However, Dientamoeba fragilis and Shiga-like toxigenic E. coli were detected significantly less frequent in cases than in controls, while no difference in prevalence was found for typical EPEC and enterohemorrhagic E. coli. The association between the presence of microorganisms and GE was the weakest in children aged 0 to 5 years. Higher relative loads in cases further support causality. This was seen for Campylobacter spp., Salmonella spp., enterotoxigenic E. coli, and C. parvum/hominis, and for certain age categories of those infected with C. difficile, enteroaggregative E. coli, and atypical EPEC. For D. fragilis and Shiga-like toxigenic E. coli/enterohemorrhagic E. coli, pathogen loads were lower in cases. Application of molecular diagnostics in GE is rapid, sensitive and specific, but results should be interpreted with care, using clinical and additional background information.
A phase I study of R547, a novel, selective inhibitor of cell cycle and transcriptional cyclin dependent kinases (CDKs)
Authors: S. Diab, S. Eckhardt, A. Tan, G. Frenette, L. Gore, W. Depinto, J. Grippo, M. DeMario, S. Mikulski, S. Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2007)

3528 Background: R547, a potent inhibitor of CDKs 1, 2, 4, 7, and 9, has shown broad antitumor activity in preclinical models. This phase Ia study assessed safety, pharmacokinetic (PK), and pharmacodynamic (PD) endpoints. Methods: R547 given as a 90 or 180 min infusion D1, D8 (21 day cycle). Key inclusion criteria: ECOG 0–2, adequate hematologic, hepatic, and renal function. Exclusion: brain metastases, NYHA III/IV CHF, CVA, current antihypertensive therapy. Blood samples on cycle 1, D1, D8 for PK and PD. PD endpoint is inhibition of retinoblastoma phosphorylation (pRB) in PBMCs. Results: 41 pts received R547 over dose range 8.6 - 195 mg/m 2 ; 31 pts on 90 min and 10 pts on 180 min schedule. Mean age 53.4 yrs (20–81), 25F:16M. Mean R547 cycles 3.1(&lt;1- 8) for 18 evaluable pts receiving doses ≥ 155 mg/m 2 . Toxicities: principal related events were nausea (54%), fatigue (34%), emesis (34%), headache (34%), and hypotension (32%). All of these limited to gr 1/ 2, except 4 gr 3 fatigue (1 in cycle 1) and 1 gr 3 nausea. DLTs: 90 min- gr 3 somnolence, gr 3 confusion, gr 3 fatigue, 1 pt each, all at 195 mg/m 2 ; 180 min- 1 DLT of prolonged gr 3 pruritis at 195 mg/m 2 . PK: Mean AUC for 20 pts with PK receiving ≥ 155 mg/m 2 R547 exceeds exposures efficacious in xenograft studies. At equivalent doses, the 180 min schedule produces equivalent AUC but 30% reduction of C max . PD: for pts with available data (n=21), an exposure-dependent decrease in pRB/total RB ratio was observed 1.5 to 24 hrs post R547. Activity: tumor regression in 1 pt with metastatic squamous ca skin; 8 additional pts received ≥ 4 cycles. Conclusions: Treatment with R547 is tolerable at a dose of 155 mg/m 2 on D1, D8 (21 day cycle) for both 90 and 180 min schedules. Nausea, emesis, headache, and transient hypotension are manageable with anti-emetic, analgesic, and iv fluid support. The DLTs observed in the 90 min schedule have not occurred in pts receiving 180 min infusions, a schedule which maintains R547 exposure but reduces C max . Exposures predictive of preclinical efficacy have been achieved. Inhibition of a relevant PD marker (pRB) and antitumor activity have each been confirmed in the clinic. Phase II trials in advanced solid tumors and hematologic malignancies are planned. No significant financial relationships to disclose.
LSC 2013 abstract - Identification of biomarkers for early diagnosis in BPD
Authors: Tina Gimm, Anita Hoeland, Maren Schwarz, Hamid Hossain, Harald Ehrhardt, Ludwig Gortner, Markus Scholz, Tobias Reicherzer, Stefanie Hauck, Anne Hilgendorff
Journal: European Respiratory Journal (2013)

Rationale:  Bronchopulmonary dysplasia (BPD), one of the most common complications in the preterm infant, is characterized by impaired alveolar and vessel development. Mechanical ventilation, oxygen toxicity and infections increase the risk for BPD with impaired pulmonary and neurologic outcome persisting into adulthood. Current definitions rely on late pulmonary function and reliable biomarkers allowing for an early diagnosis are still missing.   Objective and Methods:  We therefore subjected cord blood (CB) from preterms    Results:  Transcriptome analysis exhibited 102 up- and 134 down-regulated genes in preterms with BPD compared to no-BPD controls. Genes were involved in regulation of gene expression (up), or cell differentiation, embryonic development and ion homeostasis (down). Luminex analyses revealed significant differences in cytokines (sIL-1ra, IL-8, TNF-a, MCP-1) and growth factor expression (FGF2, EGF), correlating with functional data in fibroblasts from TA. First proteome data in urine and TA confirmed potential biomarker candidates.   Conclusion:  Gene expression and protein profiling from CB, urine and TA of preterms allows differentiation for later BPD diagnosis with increased monocyte signaling and fibroblast activation playing a central role.
Nocturnal hypercapnia in eucapnic obese patients With sleep disordered breathing (SDB)
Authors: Rachel Harding, Swapna Mandal, Carley King, Michelle Ramsay, Eui-Sik Suh, Nicholas Hart
Journal: European Respiratory Journal (2013)

Introduction: Obese patients with suspected SDB and hypercapnia are investigated with an arterial blood gas and overnight oximetry. We investigated the proportion of eucapnic obese patients who exhibit nocturnal hypercapnic respiratory failure. Method: Prospectively entered data from electronic patient record (Carevue, Philips, USA) from January 2012-December 2012 were analysed.Obese patients with suspected SDB attending for inpatient overnight transcutaneous carbon dioxide (TcCO2) and oxygen saturation (SpO2) monitoring were included. Results: 44 patients were assessed, of which 29 (68%) exhibited daytime eucapnia with a bicarbonate level of 26(1.7)mmols/L.21% (6/29) were eucapnic day and night.79% (23/29) of these demonstrated nocturnal hypercapnia with a mean TcCO2 of 6.5kpa and 75% of time spent with TcCO2>6kpa. 15 (34%) were hypercapnic during the day and overnight, with a mean TcCO2 of 6.8kPa and 81% of the time spent with a TcCO2 above 6kPa.

![Figure][1] 



Conclusion: These data demonstrate that the majority of obese patients referred for assessment of SDB and nocturnal hypercapnia are eucapnic during the day. However, a significant percentage develop hypercapnia overnight. The daytime bicarbonate level was within normal limits, indicating that overnight carbon dioxide monitoring must be considered in obese patients with sleep disordered breathing and eucapnia.

 [1]: pending:yes
Immunotherapy and Chemotherapy in Children With Neuroblastoma 1 2
Authors: Mark E. Nesbit, John Kersey, Jerry Finklestein, John Weiner, Richard Simmons
Journal: JNCI Journal of the National Cancer Institute (1976)

Recent advances with immunotherapy in animal tumors suggested that trials with a combination of chemotherapy and immunotherapy in human malignant tumors might be worthwhile. A pilot program with Vibrio cholera neuraminidase-treated tumor cells plus BCG was tested in 3 patients who had had chemotherapy for disseminated neuroblastoma. Two of these children were in "complete remission" after radiation therapy and chemotherapy before the administration of immunotherapy. Relapse occurred in 5–6 months in all 3 patients. These disappointing results are discussed in relation to problems of current chemotherapy in disseminated neuroblastoma including results obtained at second-look operations in patients obtaining "complete remission."
Further Studies on the Effect of Leupeptin, a Protease Inhibitor, on Induction of Bladder Tumors in Rats by N -Butyl- N -(4-hydroxybutyl)nitrosamine 2 , 3
Authors: Tadao Kakizoe, Hiroyasu Esumi, Takashi Kawachi, Takashi Sugimura, Tomio Takeuchi, Hamao Umezawa
Journal: JNCI Journal of the National Cancer Institute (1977)

The effect of a microbial protease inhibitor, leupeptin, on the induction of urinary bladder tumors in W rats by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Three groups of animals were given 0.01% BBN in their drinking water for 12 weeks. A basal powder diet supplemented with 0.1% leupeptin was given to group A throughout the experiment and to group B when BBN administration was stopped. Group C was given the basal diet without leupeptin throughout the study. The total preservation period was 40 weeks. Results clearly showed that when leupeptin was given during the promotion step of bladder carcinogenesis (as in group B), it increased the size of tumors and the incidences of cancer and invasion. When leupeptin was given throughout the experiments, its effect was counteracted (as in group A).
Immunotherapy of Cancer: Regression of Intradermal Tumors and Prevention of Growth of Lymph Node Metastases After Intralesional Injection of Living &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt;
Authors: Berton Zbar, Irwin D. Bernstein, Gerald L. Bartlett, Michael G. Hanna, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1972)

Intradermal (ID) inoculation of cells of a syngeneic transplantable ascites guinea pig hepatocarcinoma led to a progressively growing 10 tumor. Tumor cells metastasized to the regional lymph node by 6–7 days after tumor implantation. Excision or irradiation of the tumor prevented tumor growth locally but did not prevent metastases from growing and killing the host. Specific immunization did not impair growth of established 10 tumors or growth of tumor in the draining lymph node. Inoculation of living bacillus Calmette-Guerin (BCG) organisms into established 10 tumors caused local tumor regression and prevented growth of tumor cells present in the regional lymph node. Intratumor (IT) injection of BCG led to complete tumor regression in 63% of guinea pigs with tumor nodules weighing 95 mg and in 16% of guinea pigs with tumor nodules weighing 425 mg. Guinea pigs treated by IT injection of BCG developed systemic tumor immunity; some animals rejected distant artificial metastases.
Metabolic Studies on Mechanism of Urethan Action. IV. Influence of Urethan on Nucleic Acid Metabolism in Rapidly Proliferating Tissues &lt;italic&gt;In Vivo&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. P. Giri, S. V. Bhide
Journal: JNCI Journal of the National Cancer Institute (1969)
Methotrexate-induced renal impairment: clinical studies and rescue from systemic toxicity with high-dose leucovorin and thymidine.
Authors: H T Abelson, M T Fosburg, G P Beardsley, A M Goorin, C Gorka, M Link, D Link
Journal: Journal of Clinical Oncology (1983)

Four separate groups of patients have been studied: (1) The effect of high-dose methotrexate (MTX) administration on glomerular filtration rate was determined by pre- and posttreatment inulin and creatinine clearances in nine patients. Measurements were made prior to and 24-40 hr after drug administration. Inulin and creatinine clearances both decreased a mean of 43%. No signs of systemic toxicity occurred. (2) Three other patients given high-dose courses of MTX developed MTX toxicity. Their creatinine clearance decreased an average of 61%. (3) In a separate group of five patients undergoing weekly MTX treatment, comparison of serum MTX pharmacokinetics with and without alkalinization of the urine demonstrated no significant difference in peak serum MTX levels or serum MTX decay. (4) Eight additional patients with severe renal dysfunction secondary to MTX were treated with increased doses of leucovorin and a continuous infusion of thymidine (8 g/m2/day) once renal failure was recognized. When high-dose leucovorin and thymidine were begun 48-72 hr after the MTX infusion, severe toxicity in the form of leukopenia, thrombocytopenia, diffuse mucositis, stomatitis, or skin rash was averted. We concluded the following: (1) high-dose MTX causes a subclinical decrease in glomerular filtration rate with each administration, even in nontoxic courses; (2) alkalinization of the urine with sodium bicarbonate does not alter plasma MTX decay, while volume expansion (hydration) is maintained constant; and (3) rigorous monitoring of serum creatinine and serum MTX levels 24-48 hr after MTX administration allows for the institution of rescue measures, including leucovorin and thymidine, which will abort the systemic toxicity that accompanies MTX-induced renal failure.