nils-herrmann/clean_scirepeval huggingface dataset:
Phase I and pharmacological study of oral 9-aminocamptothecin colloidal dispersion (NSC 603071) in patients with advanced solid tumors.

9-Aminocamptothecin colloidal dispersion (9-ACCD; NSC 603071) is a specific inhibitor of topoisomerase I that can be given p.o. This Phase I trial was conducted to determine the toxicity profile, maximal tolerated dose, and pharmacokinetics profile, including bioavailability, of p.o. 9-ACCD in patients with advanced solid tumors.



After receiving one i.v. dose of 9-ACCD, patients were treated with 9-ACCD p.o., starting with a 2-week schedule, to establish the safety. Once safety was established, patients were treated continuously for 4 weeks followed by a rest period of 2 weeks at dosages of 0.2, 0.3, 0.45, 0.56, 0.7, and 0.63 mg/m(2)/day. Serial blood samples were collected for the pharmacokinetics study on day 1 after the i.v. dose and day 2 after p.o. administration. Lactone and total 9-aminocamptothecin were analyzed by high-pressure liquid chromatographic assay.



Thirty-two patients were treated on the study. The dose-limiting toxicity was myelosuppression at the dosage of 0.7 mg/m(2)/day. Other toxic effects included nausea, vomiting, fatigue, and transient elevation of the total bilirubin level. The maximal tolerated dose was 0.63 mg/m(2)/day. There was no objective response. The mean terminal half-life of p.o. total 9-ACCD was 1.2 +/- 1.2 h, and the volume of distribution was 17.7 +/- 20.6 l/m(2). The mean bioavailability of total 9-ACCD was 68.1 +/- 36.4%.



Despite good tolerance of p.o. administration, the lack of clinical activity and variable absorption of 9-ACCD suggested that further development might not be warranted.
Predicting Noninsulin Antidiabetic Drug Adherence Using a Theoretical Framework Based on the Theory of Planned Behavior in Adults With Type 2 Diabetes

Understanding the process behind noninsulin antidiabetic drug (NIAD) nonadherence is necessary for designing effective interventions to resolve this problem. This study aimed to explore the ability of the theory of planned behavior (TPB), which is known as a good predictor of behaviors, to predict the future NIAD adherence in adults with type 2 diabetes. We conducted a prospective study of adults with type 2 diabetes. They completed a questionnaire on TPB variables and external variables. Linear regression was used to explore the TPB's ability to predict future NIAD adherence, which was prospectively measured as the proportion of days covered by at least 1 NIAD using pharmacy claims data. The interaction between past NIAD adherence and intention was tested. The sample included 340 people. There was an interaction between past NIAD adherence and intention to adhere to the NIAD (P = 0.032). Intention did not predict future NIAD adherence in the past adherers and nonadherers groups, but its association measure was high among past nonadherers (β = 5.686, 95% confidence interval [CI] -10.174, 21.546). In contrast, intention was mainly predicted by perceived behavioral control both in the past adherers (β = 0.900, 95% CI 0.796, 1.004) and nonadherers groups (β = 0.760, 95% CI 0.555, 0.966). The present study suggests that TPB is a good tool to predict intention to adhere and future NIAD adherence. However, there was a gap between intention to adhere and actual adherence to the NIAD, which is partly explained by the past adherence level in adults with type 2 diabetes.
Evaluating the agreement between tumour volumetry and the estimated volumes of tumour lesions using an algorithm

To evaluate the agreement between tumour volume derived from semiautomated volumetry (SaV) and tumor volume defined by spherical volume using longest lesion diameter (LD) according to Response Evaluation Criteria In Solid Tumors (RECIST) or ellipsoid volume using LD and longest orthogonal diameter (LOD) according to World Health Organization (WHO) criteria. Twenty patients with metastatic colorectal cancer from the CIOX trial were included. A total of 151 target lesions were defined by baseline computed tomography and followed until disease progression. All assessments were performed by a single reader. A variance component model was used to compare the three volume versions. There was a significant difference between the SaV and RECIST-based tumour volumes. The same model showed no significant difference between the SaV and WHO-based volumes. Scatter plots showed that the RECIST-based volumes overestimate lesion volume. The agreement between the SaV and WHO-based relative changes in tumour volume, evaluated by intraclass correlation, showed nearly perfect agreement. Estimating the volume of metastatic lesions using both the LD and LOD (WHO) is more accurate than those based on LD only (RECIST), which overestimates lesion volume. The good agreement between the SaV and WHO-based relative changes in tumour volume enables a reasonable approximation of three-dimensional tumour burden. • Tumour response in patients undergoing chemotherapy is assessed using CT images • Measurements are based on RECIST (unidimensional)-based or WHO (bidimensional)-based criteria • We calculated tumour volume from bidimensional target lesion measurements • This formula provides good tumour volume approximation, based on semiautomated volumetry
Impact of Home-Based Exercise Training with Wireless Monitoring on Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

Recent studies have suggested a favorable effect of cardiac rehabilitation (CR) on patients with cardiovascular disease. This study aimed to evaluate the impact of home-based exercise training with wireless monitoring on acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). A total of 55 ACS patients undergoing PCI were randomly divided into home based exercise training with wireless monitoring cardiac rehabilitation (CR, n = 26) and usual care (UC, n = 29). Exercise capacity and quality of life (QOL) were evaluated at baseline and after 12 weeks. Change of metabolic equivalent of the tasks, maximal exercise time and QOL were significantly increased (+2.47 vs +1.43, P = 0.021; +169.68 vs +88.31 sec, P = 0.012; and +4.81 vs +0.89, P = 0.022, respectively), and the change of submaximal rate pressure product, and of submaximal rate of perceived exertion were significantly decreased (-28.24 vs -16.21, P = 0.013; and -1.92 vs -1.62, P = 0.018, respectively) in the CR group compared to the UC group after 12 weeks. CR using home-based exercise training with wireless monitoring led to improvement of exercise capacity and QOL relative to conventional care in ACS patients undergoing PCI. Our findings suggest that early scheduled CR may be considered in ACS patients undergoing PCI.
Olmesartan medoxomil plus amlodipine increases efficacy in patients with moderate-to-severe hypertension after monotherapy: a randomized, double-blind, parallel-group, multicentre study.

Hypertension remains a major global health problem, and evidence suggests that the majority of patients will require two or more antihypertensive agents in order to reach specified BP targets. Combining two drugs from different classes has the potential to target different aspects of hypertension, which may result in additional BP decreases compared with either agent used alone. This randomized, double-blind, parallel-group, multicentre trial in patients with moderate-to-severe hypertension (systolic BP [SBP]/diastolic BP [DBP] > or =160/100 mmHg) investigated the additional efficacy in BP reduction and BP goal rates (<140/90 mmHg for patients without diabetes mellitus, <130/80 mmHg for patients with diabetes) achieved by adding amlodipine 5 or 10 mg/day to olmesartan medoxomil (hereafter olmesartan) 20 mg/day in patients not adequately controlled on olmesartan monotherapy.



After 8 weeks' open-label olmesartan 20 mg monotherapy, 538 patients with SBP/DBP > or =140/90 mmHg were randomized to 8 weeks' double-blind therapy with olmesartan/placebo, olmesartan/amlodipine 20 mg/5 mg or olmesartan/amlodipine 20 mg/10 mg. 
After 8 weeks (with last observation carried forward), the adjusted mean change in seated DBP (SeDBP) from baseline was -7.6 mmHg for olmesartan/placebo, -10.4 mmHg for olmesartan/amlodipine 20 mg/5 mg (p = 0.0006 vs olmesartan/placebo) and -10.9 mmHg for olmesartan/amlodipine 20 mg/10 mg (p < 0.0001 vs olmesartan/placebo). Mean changes in SeSBP from baseline with olmesartan/amlodipine 20 mg/5 mg and olmesartan/amlodipine 20 mg/10 mg were -16.1 and -16.7 mmHg, respectively (p < 0.0001 for both dose regimens vs olmesartan/placebo). BP goal rates were significantly higher with olmesartan/amlodipine 20 mg/5 mg and olmesartan/amlodipine 20 mg/10 mg (44.5% and 45.8%, respectively; p = 0.0011 and p = 0.0004, respectively) versus olmesartan/placebo (28.5%). Combination therapy was well tolerated, and the incidence of drug-related adverse events was 8.9% for olmesartan/placebo, 7.7% for olmesartan/amlodipine 20 mg/5 mg, and 11.3% for olmesartan/amlodipine 20 mg/10 mg (p = 0.490). Most adverse events were mild in severity and were well known drug-class issues.



Combining olmesartan and amlodipine resulted in significantly greater BP lowering in patients not achieving adequate BP control with olmesartan monotherapy, thus allowing a significantly greater proportion of patients to achieve BP goal.
Mucolytic Effectiveness of Tyloxapol in Chronic Obstructive Pulmonary Disease - A Double-Blind, Randomized Controlled Trial

Mucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD.



A randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol.



A comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34-5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73-3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV1, RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure.



Our study demonstrated that inhalation of Tyloxapol by patients with COPD is safe and superior to saline and has some anti-inflammatory effects.
A two year randomised controlled trial of intramuscular depot steroids in patients with established rheumatoid arthritis who have shown an incomplete response to disease modifying antirheumatic drugs.

In rheumatoid arthritis (RA), intramuscular (IM) pulsed depomedrone expedites an immediate response to disease modifying antirheumatic drugs (DMARDs). Although IM depomedrone is also widely used to treat disease flares in patients treated with DMARDs, its effect on radiological progression has not been assessed.



To evaluate the benefits of 120 mg IM depomedrone versus placebo in patients with established RA whose disease was inadequately controlled by existing DMARDs.



In a 2 year prospective randomised controlled trial patients were assessed using the ILAR/WHO core dataset, disease activity score (DAS28), x ray examination of hands and feet scored by Larsen's method, and bone densitometry.



291 patients with RA were screened, 166 were eligible, and 91 consented and were randomised. Disease activity improved more rapidly in the steroid treated patients than with placebo, but after 6 months no difference remained. A small but significant reduction in erosive damage in the steroid group compared with placebo was also found. More adverse reactions occurred in the steroid treated group than in the placebo patients (55 v 42), especially those reactions traditionally related to steroids (16 v 2), including vertebral fracture, diabetes, and myocardial infarction. Hip bone density fell significantly in steroid treated but not placebo patients.



IM depomedrone improved disease activity in the short term and produced a small reduction in bone erosion at the cost of a significant increase in adverse events. Despite the initial benefit of IM depomedrone, when patients respond suboptimally to a DMARD they should not be given long term additional steroids but should be treated with alternative or additional DMARDs.
[Efficacy of tiotropium bromide (Spiriva) in patients with chronic-obstructive pulmonary disease (COPD) of different severities].

Aim of this study was to evaluate the efficacy of inhaled Tiotropium bromide in COPD patients of different severities in pneumological practices during a three months clinical trial.



A randomized, double blind, placebo controlled study including COPD-patients (FEV1/FVC < 70 %, FEV1 < or = 70 % predicted; age > or = 40 years; > or = 10 pack years) of different severities was performed. The efficacy of 18 microg Tiotropium bromide once daily on lung function and exacerbations over 12 weeks was evaluated by respective pulmonary function tests (spirometry) before (trough value) and 2 hours after inhalation of study medication.



1639 patients (1236 Tiotropium bromide, 403 placebo; FEV1 reversibility after 200 microg Ipratropium bromide + 200 microg Fenoterol: 7.9 +/- 7.5 % predicted [mean +/- sd]) were randomized. After 12 weeks of treatment Tiotropium bromide led to significant increases of trough FEV1 (23 - 24 h after last inhalation; + 79 +/- 17 ml), and 2 h after Tiotropium bromide inhalation (+ 128 +/- 19 ml) (all values vs. placebo, adjusted mean +/- se, p < 0.0001). FVC and IVC were also improved significantly. In mild COPD (FEV1 > or = 50 - 70 %) improvements were most pronounced (trough FEV1 + 113 +/- 29 ml, 2 h post-inhalation + 181 +/- 33 ml; all values vs. placebo., p < 0.0001). 14.6 % of patients treated with Tiotropium bromide had a COPD exacerbation vs. 19.9 % of patients treated with placebo (p = 0.0151). The time to first exacerbation was prolonged (p = 0.0092 vs. placebo).



Tiotropium bromide 18 microg once daily led to a persistent improvement of lung function and a reduction of exacerbations in patients with COPD of different severities.
Effects of celiprolol, a cardioselective beta-blocker, on respiratory function in asthmatic patients.

The aim of this study was to compare the pulmonary effects of a single dose of celiprolol 400 mg, versus bisoprolol 20 mg and the combination of celiprolol 400 mg plus propranolol 40 mg versus placebo plus propranolol 40 mg. We conducted a double-blind randomized cross-over study in 10 stable asthmatic patients (mean age +/- SD 31 +/- 7 yrs) with forced expiratory volume in one second (FEV1): 2.5 +/- 0.7 l. A three-day washout period preceded each treatment period. Measurements of respiratory function were done before treatment and after 90, 120 and 180 min. There was a significant increase of FEV1 (+12%) and forced vital capacity (FVC) (+8%) after celiprolol (p less than 0.05) and a decrease of FEV1 (-9%) after propranolol. Concerning the combination, celiprolol inhibits the bronchoconstrictor effects of propranolol. We conclude that celiprolol has bronchosparing properties in asthmatic patients, and even improves some of the ventilatory parameters.
Effect of beta-blocker therapy on left atrial function in patients with heart failure: comparison of metoprolol succinate with carvedilol

We aimed to compare the effects of carvedilol and metoprolol succinate on left atrial (LA) function in patients with chronic heart failure. Thirty three patients (6 females, 27 males) who had not received β blocker treatment previously and whose left ventricular ejection fraction was below 40% were included in this study. LA volumes were measured echocardiographically just before the time of mitral valve opening (V max), onset of atrial systole (p-wave at the electrocardiography = V p) and mitral valve closure (V min) according to the biplane area length method at baseline and in the 3rd month after the administration of β blockers. NT-proBNP level was measured at the beginning and in the third month of β blocker treatment. The first group was given carvedilol 6.25 mg/day, the second group was given 12.5 mg/day metoprolol succinate and it was increased to the tolerable maximal dose. LA diameter and LA V max, V p, V min decreased significantly both in carvedilol group and metoprolol group after β blocker theraphy (P  < 0.01, P  < 0.01, P  < 0.05, P < 0.05 for metoprolol, P < 0.001, P < 0.01, P < 0.01, P < 0.01 for carvedilol). But it was increased in conduit volume (P < 0.05 for two groups). LA-passive emptying fraction, LA-active emptying fraction and reservoir fraction were no significant differences both in carvedilol group and metoprolol group after β blocker theraphy. NT-proBNP levels were found to decrease significantly in both groups after β blocker treatment (P < 0.001). Our findings indicate that β blocker treatment leads to a decrease in LA diameters and volumes, and metoprolol succinate and carvedilol had similar effects on this decrease.
Peer-led education for adolescents with asthma in Jordan: a cluster-randomized controlled trial.

To determine the impact of a peer-led education program, developed in Australia, on health-related outcomes in high school students with asthma in Jordan.



In this cluster-randomized controlled trial, 4 high schools in Irbid, Jordan, were randomly assigned to receive the Adolescent Asthma Action program or standard practice. Bilingual health workers trained 24 peer leaders from Year 11 to deliver asthma education to younger peers from Year 10 (n = 92), who in turn presented brief asthma skits to students in Years 8 and 9 (n = 148) and to other members of the school community in the intervention schools. Students with asthma (N = 261) in Years 8, 9, and 10 completed baseline surveys in December 2006 and 3 months after the intervention.



Students from the intervention group reported clinically significant improvements in health-related quality of life (mean difference: 1.35 [95% confidence interval: 1.04-1.76]), self-efficacy to resist smoking (mean difference: 4.63 [95% confidence interval: 2.93-6.35]), and knowledge of asthma self- management (mean difference: 1.62 [95% confidence interval: 1.15-2.19]) compared with the control group.



This trial demonstrated that the Adolescent Asthma Action program can be readily adapted to suit different cultures and contexts. Adolescents in Jordan were successful in teaching their peers about asthma self-management and motivating them to avoid smoking. The findings revealed that peer education can be a useful strategy for health promotion programs in Jordanian schools when students are given the opportunity and training.
Shearer's Manual of Human Dissection

of growth and development as the chief features which distinguish infants and children from adults. This section includes somewhat diverse subdivisions on disturbances of growth, constitutional signs and symptoms such as fever and edema, symptoms referable to particular systems such as the urinary tract, and symptoms related to sexual development and to intellectual retardation. Within each subdivision of this section an attempt is made to list the conditions in which the designated symptom is encountered and to present some information concerning the mechanism of its development. These explanations are necessarily brief and were not intended to be complete; they vary considerably in effectiveness. The final section on health supervision gives consideration to the prenatal period, infancy, the preschool period, the school years, and adolescence. An appendix includes in tabular form familiar percentiles for weight, height, and other selected measurements in different age groups. The book is attractively composed and in regard to both style and typography is easy to read. Incorporated into the text are numerous up-to-date references which directly accompany the subjects to which they refer. This arrangement, devised by the authors to encourage more intensive study, is an effective innovation. The index, although extensive, could be more serviceable if more complete. For example, the common terms croup, salicylates, hysteria, intoxication, and poisoning are not listed alphabetically; similarly, calcification in the skin is listed but not pulmonary or intracranial calcification. This book does not pretend to impart new knowledge of pediatrics but rather a new approach to existing knowledge. It will not replace nor was it intended to be a substitute for more comprehensive texts including Gross's Sutrgery of infancy and childhood to which frequent reference is made. Its chief value would seem to be as a guide to further reading and to a better understanding of those aspects of pediatrics with which this book is concerned. EDWARD C. CURNEN
Genome-wide estimation of transcript concentrations from spotted cDNA microarray data

A method providing absolute transcript concentrations from spotted microarray intensity data is presented. Number of transcripts per microg total RNA, mRNA or per cell, are obtained for each gene, enabling comparisons of transcript levels within and between tissues. The method is based on Bayesian statistical modelling incorporating available information about the experiment from target preparation to image analysis, leading to realistically large confidence intervals for estimated concentrations. The method was validated in experiments using transcripts at known concentrations, showing accuracy and reproducibility of estimated concentrations, which were also in excellent agreement with results from quantitative real-time PCR. We determined the concentration for 10,157 genes in cervix cancers and a pool of cancer cell lines and found values in the range of 10(5)-10(10) transcripts per microg total RNA. The precision of our estimates was sufficiently high to detect significant concentration differences between two tumours and between different genes within the same tumour, comparisons that are not possible with standard intensity ratios. Our method can be used to explore the regulation of pathways and to develop individualized therapies, based on absolute transcript concentrations. It can be applied broadly, facilitating the construction of the transcriptome, continuously updating it by integrating future data.