tbuckley/cabot-search huggingface dataset:
Factors predictive of the short- and long-term efficacy of growth hormone treatment in prepubertal children with chronic renal failure. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.
Authors: D Haffner, E Wühl, F Schaefer, R Nissel, B Tönshoff, O Mehls
Journal: Journal of the American Society of Nephrology (1998)

To evaluate the growth-stimulating effects of short- and long-term treatment with recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal failure (CRF), 103 prepubertal children with CRF on conservative treatment (n = 74) or dialysis (n = 29) were treated with rhGH for up to 5 yr. rhGH treatment persistently increased standardized height (+ 1.6 SD scores) and predicted adult height (+7.7 cm, Tanner method) during the first 3 treatment years (P < 0.001 versus baseline), followed by percentile parallel growth during continued treatment. Both standardized height and predicted adult height were significantly more increased in conservatively treated than in dialyzed children (P < 0.001). Age, GFR, target height, and prestudy growth rate were identified as independent predictors of the response to rhGH treatment during the first and second treatment year. GFR and target height were positively correlated with the change in height SD score and the change in absolute or age-standardized height velocity. Age affected the growth response depending on which outcome measure was used: Although the first-year change in height SD score was inversely correlated with age, the change in absolute height velocity was independent of age, and the change in standardized height velocity was positively correlated with age. The growth response during the first treatment year positively predicted the long-term response. In conclusion, the short- and long-term growth response to rhGH treatment in prepubertal growth-retarded children with CRF is significantly affected by age, GFR, target height, and the pretreatment growth rate. Therefore, rhGH should be preferably started at a young age, and early in the course of CRF.
Bedaquiline and multidrug-resistant tuberculosis: a systematic and critical analysis of the evidence
Authors: Emanuele Pontali, Giovanni Sotgiu, Lia D'Ambrosio, Rosella Centis, Giovanni Battista Migliori
Journal: European Respiratory Journal (2016)

The importance of adequately managing multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) cases for TB control and elimination are underlined in the new World Health Organization (WHO) "End TB Strategy" [1, 2] as part of pillar one (integrated, patient-centred care and prevention; element 2: treatment of all people with TB including drug-resistant TB, and patient support) and in the recently published "Framework towards TB elimination in low incidence countries" in its priority action 5 (optimise the prevention and care of drug-resistant TB) and the related background documents [3–5]. Furthermore, both in the End TB Strategy (pillar 3: intensified research and innovation) and in the Framework towards TB elimination in low incidence countries (priority action 7: invest in research and new tools) the need for new anti-TB drugs is strongly emphasised [1, 3, 6]. The reasons why new anti-TB drugs are needed are rather obvious if you look closely at the dimensions of the MDR-TB epidemic and the treatment successes achieved so far. Systematic review of the available scientific evidence on the role of bedaquiline in new effective M/XDR-TB regimens <http://ow.ly/V68ZF>
Study of S91 Mouse Melanomas by Electron Paramagnetic Resonance Spectroscopy and Tissue Culture. I. The Effect of Cysteine on Blue Light Signals and on Growth &lt;italic&gt;In Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Phillip S. Duke, B.S., William Landgraf, B.S., Ph.D., Akio E. Mitamura, M.D., Harry B. Demopoulos, M.D.
Journal: JNCI Journal of the National Cancer Institute (1966)

Low-speed-cleared sucrose homogenate prepared from S91 mouse melanomas save a specific electron paramagnetic resonance (EPR) signal on irradiation with blue light. The specific signal was a well-defined doublet, and cysteine at 1 mg/ml enhanced this irradiation-produced doublet signal. The ability to give the doublet was largely lost after irradiation with blue light for 5 minutes in the presence of cysteine at 10 mg/ml. A broad, nondoublet signal was present too. EPR signals from a dialyzed and boiled homogenate preparation were examined also and the doublet signal was largely absent. The homogenate broad signal is presumably due to melanin. The homogenate doublet signal is probably related to melanin semiquinone intermediates. Cysteine at 10 mg/ml reduced the irradiation-produced spin concentrations about 75%. Cysteine showed a selective growth inhibitory action on S91 mouse melanomas versus hearts of newborn mice expiants in vitro. Growth response data are presented in the 0.30–10.0 mg/ml concentration range. The mechanisms of action of cysteine are probably due to its inhibition of tyrosinase activity by several mechanisms. The mechanisms are briefly discussed.
Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response
Authors: S. Oren, M. Mandelboim, Y. Braun-Moscovici, D. Paran, J. Ablin, I. Litinsky, D. Comaneshter, D. Levartovsky, E. Mendelson, R. Azar, I. Wigler, A. Balbir-Gurman, D. Caspi, O. Elkayam
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To assess the effect of rituximab on the efficacy and safety of influenza virus vaccine in patients with rheumatoid arthritis (RA). <h3>Methods:</h3> The study group comprised patients with RA treated with conventional disease-modifying drugs with or without rituximab. Split-virion inactivated vaccine containing 15 μg haemagglutinin/dose of B/Shanghai/361/02 (SHAN), A/New Caledonian/20/99 (NC) (H1N1) and A/California/7/04 (CAL) (H3N2) was used. Disease activity was assessed by the number of tender and swollen joints, duration of morning stiffness and evaluation of pain on the day of vaccination and 4 weeks later. CD19-positive cell levels were assessed in rituximab-treated patients. Haemagglutination inhibition (HI) antibodies were tested and response was defined as a greater than fourfold rise 4 weeks after vaccination or seroconversion in patients with a non-protective baseline level of antibodies (&lt;1/40). Geometric mean titres (GMT) were calculated in all subjects. <h3>Results:</h3> The participants were divided into three groups: RA (n = 29, aged 64 (12) years), rituximab-treated RA (n = 14, aged 53 (15) years) and healthy controls (n = 21, aged 58 (15) years). All baseline protective levels of HI antibodies and GMT were similar. Four weeks after vaccination, there was a significant increase in GMT for NC and CAL antigens in all subjects, but not for the SHAN antigen in the rituximab group. In rituximab-treated patients, the percentage of responders was low for all three antigens tested, achieving statistical significance for the CAL antigen. Measures of disease activity remained unchanged. <h3>Conclusion:</h3> Influenza virus vaccine generated a humoral response in all study patients with RA and controls. Although the response was significantly lower among rituximab-treated patients, treatment with rituximab does not preclude administration of vaccination against influenza.
Prognosis of hepatocellular carcinoma (HCC): Comparison of four staging systems in two French clinical trials
Authors: S. Collette, F. Bonnetain, X. Paoletti, M. Doffoel, O. Bouche, J. L. Raoul, P. Rougier, F. Masskouri, L. Bedenne, J. C. Barbare
Journal: Journal of Clinical Oncology (2007)

4589 Background: The aims of our study were to compare performances of 4 staging systems and to explore how to improve prognostic classification among French patients with HCC whose main aetiology is alcoholic cirrhosis. Methods: We have pooled 2 RCTs in palliative condition from Federation Francophone de Cancerologie Digestive (FFCD): - FFCD 9403 comparing tamoxifen vs symptomatic treatment and - FFCD 9402 comparing chemoembolization + tamoxifen vs tamoxifen alone. They had respectively included 416 and 122 patients. Performance of Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer group (BCLC) and GRoupe d’Etude et de Traitement du Carcinome Hépatocellulaire scores have been compared using: Akaike information criteria (AIC), discriminatory ability (Harrell’s c and the Royston’s D statistics), monocity of gradients and predictive accuracy (Schemper statistics Vs). To explore how to improve classifications univariate and multivariate Cox model were performed. Variables with univariate p&lt; 0.10 have been retained for multivariate analyses. A forward selection procedure has then been implemented. Bootstraps validation was performed to test the robustness of our results. Analyses were done for each trial and for the pooled database with trial stratification. Results: Median OS was 5,3 months (IC 95%: [4,6; 6,2]), 402 patients had (75%) an alcoholic cirrhosis aetiology . As shown in Table 1 , CLIP staging had the best properties, followed by Okuda and BCLC. Performances of all staging systems were rather disappointing. WHO staging for CLIP or alphafetoprotein for BCLC allowed a significant improvement of prognostic information. Conclusions: Our results suggest that CLIP staging seems to be most adapted to french patients, it could be better by associating WHO PS. An external validation of our result will be performed on another trial in palliative condition. [Table: see text] No significant financial relationships to disclose.
Randomized phase II study of vandetanib (VAN) alone or in combination with carboplatin and paclitaxel (CP) as first-line treatment for advanced non-small cell lung cancer (NSCLC)
Authors: J. Heymach, L. Paz-Ares, F. De Braud, M. Sebastian, D. J. Stewart, W. Eberhardt, R. S. Herbst, A. Krebs, P. Langmuir, B. E. Johnson
Journal: Journal of Clinical Oncology (2007)

7544 Background: VAN (ZD6474) is a once-daily oral agent that selectively inhibits VEGFR, EGFR and RET signaling. This randomized phase II trial investigated VAN alone or in combination with CP vs CP. Methods: Eligible patients (pts) had previously untreated locally advanced or metastatic (IIIB-IV) NSCLC. The primary objective was to determine whether VAN (300 mg/day) ± CP (C, target AUC ss = 6 mg/ml·min; P; 200 mg/m 2 iv) prolonged progression-free survival (PFS) vs CP (75% power to detect 30% prolongation; 1-sided P=0.2). An initial run-in phase had established VAN 300 mg/day as an appropriate dose to be given with CP. Results: A total of 181 pts (median age 61 yrs, range 27–83) received VAN (n=73), VAN + CP (n=56) or CP (n=52). The primary objective was met, with VAN + CP prolonging PFS vs CP (HR = 0.76, 95% CI 0.50–1.15; P=0.098): median PFS = 24 wks (VAN + CP) and 23 wks (CP). The VAN monotherapy arm was stopped early after a planned interim PFS analysis met the criterion for discontinuation (HR &gt; 1.33 vs CP). The objective response rates were 32%, 25% and 7% for VAN + CP, CP and VAN, respectively. Overall survival (OS), a secondary endpoint, was not significantly different between pts receiving VAN + CP or CP (HR = 1.07, 95% CI 0.63–1.81; P=0.595). Exploratory subgroup analyses suggest advantages in PFS and OS for VAN + CP vs CP for the 56 female pts. There was a higher incidence of some adverse events with VAN + CP vs CP, including rash (64% vs 33%), diarrhea (53% vs 32%), asymptomatic QTc-related events (22% vs 4%) and hypertension (32% vs 4%). Pts receiving VAN + CP, including 7 who entered with CNS metastases and 11 with squamous histology, did not experience any intracranial bleeding, or hemoptysis of CTC grade 2 or higher. A biomarker analysis, including circulating endothelial cells and 35 plasma angiogenic factors and cytokines, suggests several potential markers predictive of clinical outcome and will be reported separately. Conclusions: In this randomized phase II trial of 1 st -line advanced NSCLC, VAN + CP met the primary endpoint of prolonging PFS vs CP alone but did not provide a detectable survival advantage. No significant financial relationships to disclose.
Effect of Antibody to 9 Antigen on Cell-Mediated Immunity Induced in Syngeneic Mice by Murine Sarcoma Virus 2
Authors: Ronald B. Herberrnan, Myrthel E. Nunn, David H. Lavrin, Richard Asofsky
Journal: JNCI Journal of the National Cancer Institute (1973)

Mice were immunized with murine sarcoma virus and their lymphocytes tested for cytotoxic reactivity in a 51chromlum release assay. The positive reactions obtained at 1470 days after immunization were strongly inhibited by pretreatment of the lymphocytes with anti-θ antibody and complement. An antiglobulin reagent, previously shown to inhibit lymphocyte-dependent antibody cytotoxicity, had no effect. These experiments indicated that θ-positive lymphocytes were responsible for most of the immune reactivity. In contrast, normal lymphocytes also had low levels of cytotoxic reactivity, and this was not eliminated by anti-θ.
Recombinant CD40L Treatment Protects Allogeneic Murine Bone Marrow Transplant Recipients From Death Caused by Herpes Simplex Virus-1 Infection
Authors: Janice L. Beland, Heiko Adler, Nadia C. Del-Pan, Wende Kozlow, Janice Sung, William Fanslow, Ilonna J. Rimm
Journal: Blood (1998)
A Phase (Ph) I/II Trial to Evaluate the Efficacy (E) and Safety (S) of Nab-Paclitaxel (Nab-P) in Combination (Co) with Gemcitabine (G) for the Treatment (Tr) of Frail (Fr) Patients (P) with Advanced or Metastatic Pancreatic Cancer (Apc): Safety Results of the Phase I Trial
Authors: C. Guillen-Ponce, R. Lopez, T. Macarulla, F. Rivera, A. Cubillo, A. Carrato, E. Brozos, T. Sauri Nadal, C. López, M. Hidalgo
Journal: Annals of Oncology (2014)
Single nucleotide polymorphisms in androgen-related genes and prostate cancer
Authors: M. Gos, M. Sadowska, P. Wiechno, T. Demkow, P. Janik
Journal: Journal of Clinical Oncology (2007)

21033 Background: Single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in androgen metabolism were suggested to influence the individual prostate cancer susceptibility and clinical course of the disease. To examine this correlation in Polish population, we have developed a case-control study to analyze whether SNPs in CYP17 (+34T/C), SRD5A2 (V89L and A49T) and UGT2B15 (D85Y) genes may influence prostate cancer risk. These SNPs were also examined for their correlation with clinical features of prostate cancer at diagnosis and disease progression to hormone-refractory state. Methods: The genomic DNA was extracted from blood samples from 182 men with histologically confirmed prostate cancer and 217 healthy men, randomly chosen from population. SNPs analyses were performed with standard molecular methods. Results: The case-control study has revealed that 85YY and 85DY variants in UGT2B15 were more prevalent among patients (83%) than in the control group (73.3%; p=0.02; OR=1.78). The +34CC genotype in CYP17 was more frequent in patients with distant metastasis (30.4%) than in patients with organ confined (T1/T2) or locally advanced (T3/T4) disease (10.2% and 22.6%, respectively; p&lt;0.05). This variant also correlated with higher PSA level at diagnosis. The 89LL variant in SRD5A2 was more common in patients with poorly differentiated prostate cancer (Gleason &gt;6; 17.8%) than in men with well differentiated tumor (5.4%; p=0.033, OR=3.78). The 85YY variant in UGT2B15 was more prevalent in patients that developed hormone-refractory prostate cancer within two years from the beginning of androgen blockade (47.2% vs 23.3%, p=0.025, OR=2.95). Also the analysis of progression-free survival time on hormonal therapy for D85Y polymorphism yield significant results (p=0.041, Gehan's generalized Wilcoxon test). Conclusions: The D85Y polymorphism in UGT2B15 seems to influence prostate cancer risk in Polish population. The analyzed SNPs also correlated with clinical stage and PSA level at diagnosis (+34T/C in CYP17), tumor histological grade (V89L in SRD5A2) and response to hormonal therapy (D85Y in UGT2B15). No significant financial relationships to disclose.
Three Cases of Macroprolactinaemia
Authors: A O Olukoga, T L Dornan, J W Kane
Journal: Journal of the Royal Society of Medicine (1999)

A woman with hirsutism but otherwise symptom-free was found to have a raised serum prolactin and a pituitary microadenoma. The hyperprolactinaemia persisted despite bromocriptine therapy and subsequent pituitary surgery, which yielded a non-functioning adenoma. After a further 15 years with persistent hyperprolactinaemia but no symptoms, macroprolactinaemia was diagnosed. Such cases might account for part of the failure rate of pituitary microsurgery for prolactinoma. Testing for macroprolactinaemia is advisable in a woman with hyperprolactinaemia, especially if her ovulatory cycle is normal. Two other cases are reported in which macroprolactinaemia was associated with menstrual disturbances and other hormonal effects: in these, treatment with dopamine agonists suppressed the hyperprolactinaemia and restored normal menstrual cycles.
Abstract 9181: Does a Low Ejection Fraction Predict Mortality? Insights From the ASCEND-HF Trial
Authors: Mustafa Toma, Justin A Ezekowitz, Christopher M O'Connor, Adrian F Hernandez, Jeffrey A Bakal, Muhammad Rizwan Sardar, Ronald Zolty, Barry M Massie, Paul W Armstrong, Randall C Starling
Journal: Circulation (2012)

Background: Acute heart failure (AHF) is associated with significant morbidity and mortality. Limited data exist assessing the relationship between left ventricular ejection fraction (EF) and outcomes in patients with AHF. Methods: We explored the association between EF and 30-day and 180-day mortality in AHF patients enrolled in the Acute Studies of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial. EF was analyzed as a continuous variable and as 3 categories: 50%(PresEF). Results: Of the 7007 patients in the trial, EF was available in 5687 (81.2%) patients: 4474 (78.7%) had LowEF, 674 (11.9%) had IntEF, and 539 (9.5%) had PresEF. Compared to LowEF patients, those with IntEF and Pres EF were older, more likely to be female, have atrial arrhythmias, diabetes, and higher systolic blood pressure, and lower heart rate, respiratory rate and BNP. The unadjusted 30-day and 180-day mortality was similar for LowEF (3.7%, 12.3%), IntEF (3.4%, 13.1%), and PresEF (4.3%, 14.1%), respectively (p&gt;0.05). After multivariable adjustment, the hazard ratio (HR) for 180-day mortality remained similar for the LowEF (HR 0.96, 95% CI: 0.75-1.24; p = 0.77), and IntEF (0.91, 95% CI 0.66-1.3; p = 0.58) compared to the PresEF group. By contrast, when EF was evaluated as a continuous measure, it exhibited a U-shaped relationship, i.e. the lowest risk of 30-day and 180-day death occurred at an EF of 35%. After matching for age and sex, the mortality risk attributed to EF was attenuated for patients with an EF &gt; 35%, but the mortality risk increased exponentially if the EF was &lt; 35%. (Fig. Conclusions: Among patients with AHF, 30-day and 180-day mortality is similar for those with IntEF or PresEF but increases exponentially for those with LowEF after accounting for key patient variables. Prior observations of a similar mortality risk for AHF patients with a higher EF need to be reevaluated.
Findings from the screening echocardiograms performed on survivors of childhood cancer treated with anthracyclines and/or chest radiation
Authors: J. Andolina, K. J. Dilley
Journal: Journal of Clinical Oncology (2007)

20001 Background: Treatment with anthracyclines or chest radiation confers an increased risk of cardiomyopathy persisting for years after treatment ends. The Children’s Oncology Group (COG) has created guidelines for how often to screen cardiac function in long-term survivors of pediatric cancers based on age at treatment and total cumulative dose of anthracyclines. The objective was to examine the findings from a screening program using these guidelines. Methods: Medical record reviews were performed for all patients ever seen in the past 10 years in the long-term follow-up (LTFU) program at a single institution. Reviews examined treatment variables such as diagnosis, age at diagnosis and anthracycline cumulative dose as well as the shortening fraction (SF) from any echocardiogram (echo) performed as a screening study at =4 years from diagnosis (LTFU screening echo). Analyses include Chi-square and logistic regression. Results: 365 patients seen in the LTFU program at =5 years from diagnosis were considered at risk for cardiomyopathy due to anthracycline therapy or radiation exposure to the chest (including total body irradiation). Patients were 56.4% male and 65.5% white. Acute leukemia, neuroblastoma, Wilm’s tumor and lymphoma made up 82.2% of the diagnoses. 312/365 (85.5%) had ever had an LTFU screening echo. Younger age group at treatment as divided in the COG guidelines (&lt;1y, 1–4y, =5y) was associated with likelihood of ever having an LTFU screening echo (p=0.018). 25/312 (8.0%) ever had a SF &lt;28% in one of those LTFU studies. Only 5 of those 25 had an abnormal echo prior to presenting to LTFU. Age group at treatment was not significantly associated with likelihood of a SF &lt;28% (p=0.939), but anthracycline dose of =250 mg/m 2 was associated (OR 5.9, 95% CI 2.3–15.3). Radiation exposure, stem cell transplant and history of relapse were not associated with SF &lt;28%, but prior abnormal echo was associated (p=0.032 exact). Cardiology referral was more likely in patients who ever had a SF &lt;28% (p&lt;0.001). Conclusions: Only 8% of patients being screened in a LTFU program for anthracycline-induced cardiomyopathy ever had a SF &lt;28%. Further exploration of whether the age- and dose- stratified screening guidelines can be simplified is warranted. No significant financial relationships to disclose.