nils-herrmann/clean_scirepeval huggingface dataset:
Effects of low osmolar contrast (iomeprol) on haemorheology and platelet activation in patients with coronary artery disease

Non-ionic low osmolar contrast agents are widely used during coronary angiography. As these agents cause activation of thrombotic pathways in vitro, this may have potentially significant clinical impact. However, limited evidence exists as to their in vivo effects from selective coronary cannulation. We initially performed an in vitro experiment to assess the effect of serial contrast (Iomeprol 300, Bracco) dilution on platelet indices [mean platelet count (MPC), platelet volume (MPV), platelet granularity (MPG)]. The in vivo effect of contrast injection on platelet activation markers [soluble P-selectin (sPsel), soluble CD40 ligand (sCD40L)], MPC, MPV, MPG, haemoglobin and haematocrit was subsequently determined in 35 patients (mean age 58 ± 11; 22 males) undergoing cardiac catheterisaton. No significant in vitro effect of contrast on MPC or MPV was seen but there was a significant increase in MPG (p = 0.40, 0.10 and 0.01, respectively). In the in vivo study, there was a reduction in mean haemoglobin and haematocrit levels, suggesting an average increase in plasma volume of 6.5 ± 5.8%. The in vivo effect of Iomeprol was associated with an unadjusted reduction in sPsel concentrations (p = 0.04) and MPV (p < 0.05), with denser platelets (p < 0.05). There was no difference in MPC or sCD40L concentration (both p = NS). After adjustment for the haemodilution effect, no significant reduction in P-sel levels was seen with contrast (p = 0.27), although the adjusted post-contrast change in MPG (p = 0.01), MPC (p = 0.01) and sCD40L (p < 0.05) levels were significant. Low osmolar contrast led to a minimal effect on soluble and physical indices of platelets within the coronary artery, primarily due to plasma volume expansion.
Associations of mother's and father's parenting practices with children's observed social reticence in a competitive situation: a monozygotic twin difference study.

This study used the monozygotic (MZ) twin difference method to examine whether the unique environmental effects of maternal and paternal overprotection and hostility at the age of 30 months predict twins' observed social reticence in a competitive situation in kindergarten, while controlling for the effect of family-wide influences, including genetic and shared environmental factors, family socio-economical status and twin's birth weight. It was also examined whether these associations are moderated by parental depressive symptoms. Participants were 137 MZ twin pairs who were part of an ongoing longitudinal study. Hierarchical linear regressions revealed that differences in maternal and paternal overprotection predicted differences in twins' social reticence, albeit only in boys. Differences in paternal hostile parenting predicted differences in girls' reticent behavior, but only when fathers showed high levels of depressive symptoms. Hence, overprotected boys, as well as girls confronted with father's hostility and depressive symptoms, may tend to withdraw rather than face the challenge when experiencing difficult social situations such as competition. The results from the present study suggest that targeting maladaptive maternal as well as paternal child-rearing practices and psychopathology early on may be useful for reducing later internalizing behavior in the offspring.
Dextrin sulfate as a vaginal microbicide: randomized, double-blind, placebo-controlled trial including healthy female volunteers and their male partners.

This randomized, placebo-controlled trial assessed the safety and acceptability of vaginally administered 0.125% dextrin sulfate (DS) gel in sexually active women and their male partners. A single 2-mL dose of study gel was self-administered every night over two 14-day periods separated by a 7-day interval, during which menses was expected to occur. Up to two supplementary doses per 24 hours were provided for use before sexual intercourse. Semistructured interview, colposcopy, and laboratory safety studies were used to assess adverse events. Male partners who agreed to participate in a substudy were exposed to gel through sexual intercourse during the second 14-day exposure period. Seventy-three women (36 DS recipients and 37 placebo recipients) used at least one application of gel, of whom 66 (33 DS recipients and 33 placebo recipients) completed follow-up. Eleven women (5 DS recipients and 6 placebo recipients) reported intermenstrual bleeding during gel use, which in most cases was light and resolved within 24 hours. Ten male partners (4 with DS exposure and 6 with placebo exposure) were enrolled in the study and all completed follow-up. There was no evidence of systemic toxicity or genital epithelial disruption attributable to DS gel.
Inhibition by phospholipid liposomes of the prolactin and cortisol response to insulin hypoglycemia in man

This study was designed to further investigate the purported dopaminergic activity of phospholipid liposomes (PL) prepared from bovine cerebral extracts, and to obtain further indications about their pituitary or suprapituitary site of action. In eight normal subjects, we have studied the effects of PL administration (250 mg as IV bolus plus additional 250 mg infused IV over a 60-min period), compared to placebo, on the prolactin (PRL), cortisol and growth hormone (GH) response to an insulin tolerance test (ITT). In eight additional subjects, the effects of PL on the PRL and TSH response to TRH were evaluated. PL medication blunted the PRL and cortisol response in the ITT: significant differences, with respect to placebo administration, were observed between mean peak PRL values (51.9±13.63 SEM vs 83.4±26.35 ng/ml, P<0.05) and mean cortisol values at 120 min time (20.9±0.67 vs 26.7±2.46 μg/dl, P<0.05). In contrast, PL administration did not modify the ITT-related GH rise or the PRL and TSH release in response to TRH. These findings favour the view that PL are endowed with intrinsic biological activity which is dopamine-mediated, and point to the hypothalamus as their primary site of action.
SAMITAL® improves chemo/radiotherapy-induced oral mucositis in patients with head and neck cancer: results of a randomized, placebo-controlled, single-blind Phase II study

This randomised, placebo-controlled single-blind trial investigated the safety and efficacy of SAMITAL®, a formulation of highly standardised botanical extracts, in the treatment of chemo/radiotherapy-induced oral mucositis (OM) in patients with head and neck cancer. Patients received SAMITAL® or placebo four times daily for up to 50 days during scheduled chemo/radiotherapy. Severity of OM was monitored according to a modified WHO severity scale, and pain and quality-of-life assessments were based on the effect of symptoms of OM on relevant daily activities, according to a visual analogue scale. Mean scores for the severity of OM were significantly (p < 0.05 versus baseline) reduced from day 31 until the end of treatment in patients treated with SAMITAL® (n = 20). No significant improvement was observed in the placebo group (n = 10). Pain reduction was significant from day 4 till end of treatment with SAMITAL® and from days 7 to 21 in placebo patients. SAMITAL® also significantly improved quality of life, as shown by improvements in scores for relevant daily activities including eating, drinking and sleeping. All SAMITAL® patients completed the treatment period, but no placebo recipients completed treatment. No severe adverse events were observed with SAMITAL®, and systemic absorption of relevant active ingredients was undetectable. SAMITAL® significantly decreased the severity of chemo/radiotherapy-induced OM in patients with head and neck cancer, with no treatment-related adverse events. Pain relief lasted through the treatment period, and improvements in quality of life were reflected by the significant benefits of SAMITAL® on activities like drinking, eating and speaking.
Is Metabolic Flexibility Altered in Multiple Sclerosis Patients?

Metabolic flexibility is defined as ability to adjust fuel oxidation to fuel availability. Multiple sclerosis (MS) results in reduced muscle strength and exercise intolerance. We tested the hypothesis that altered metabolic flexibility contributes to exercise intolerance in MS patients.



We studied 16 patients (all on glatiramer) and 16 matched healthy controls. Energy expenditure (EE), and carbohydrate (COX) and lipid oxidation (LOX) rates were determined by calorimetry, before and after an oral glucose load. We made measurements either at rest (canopy device) or during 40 min low-grade (0.5 W/kg) exercise (metabolic chamber). We also obtained plasma, and adipose tissue and skeletal muscle dialysate samples by microdialysis to study tissue-level metabolism under resting conditions.



At rest, fasting and postprandial plasma glucose, insulin, and free fatty acid levels did not differ between patients and controls. Fasting and postprandial COX was higher and LOX lower in patients. In adipose, fasting and postprandial dialysate glucose, lactate, and glycerol levels were higher in patients vs. controls. In muscle, fasting and postprandial dialysate metabolite levels did not differ significantly between the groups. During exercise, EE did not differ between the groups. However, COX increased sharply over 20 min in patients, without reaching a steady state, followed by an immediate decrease within the next 20 min and fell even below basal levels after exercise in patients, compared to controls.



Glucose tolerance is not impaired in MS patients. At rest, there is no indication for metabolic inflexibility or mitochondrial dysfunction in skeletal muscle. The increased adipose tissue lipolytic activity might result from glatiramer treatment. Autonomic dysfunction might cause dysregulation of postprandial thermogenesis at rest and lipid mobilization during exercise.
Phase I dose escalation and pharmacokinetic study of oral gefitinib and irinotecan in children with refractory solid tumors

This phase I study endeavored to estimate the maximum tolerated dose and describe the dose-limiting toxicities (DLTs) of oral irinotecan with gefitinib in children with refractory solid tumors. Oral irinotecan was administered on days 1–5 and 8–12 with oral gefitinib (fixed dose, 150 mg/m2/day) on days 1–12 of a 21-day course. The escalation with overdose control method guided irinotecan dose escalation (7 dose levels, range 5–40 mg/m2/day). Sixteen of 19 patients were evaluable, with serial pharmacokinetic studies in ten patients. Diagnoses included osteosarcoma (N = 5), neuroblastoma (N = 3), sarcoma (N = 3), and others (N = 5). Patients received a median of two courses (range 1–20), with at least two patients treated on dose levels 2–7. Three patients had five DLTs; the most common being metabolic (hypokalemia, N = 2 and hypophosphatemia, N = 1) at dose levels two (10 mg/m2) and four (20 mg/m2). One patient experienced grade 3 diarrhea (40 mg/m2). Irinotecan bioavailability was 2.5-fold higher when co-administered with gefitinib, while the conversion rate of irinotecan to SN-38 lactone was unaffected. The study closed due to poor accrual before evaluation of the next recommended irinotecan dose level (35 mg/m2). Of 11 patients receiving at least two courses of therapy, three had stable disease lasting two to four courses and one patient maintained a complete response through 18 courses. The combination of oral gefitinib and irinotecan has acceptable toxicity and anti-tumor activity in pediatric patients with refractory solid tumors. Pharmacokinetic analysis confirms that co-administration of gefitinib increases irinotecan bioavailability leading to an increased SN-38 lactone systemic exposure.
Randomized trial of rapamycin- and paclitaxel-eluting stents with identical biodegradable polymeric coating and design.

This prospective, randomized study sought to directly compare the performance of paclitaxel and rapamycin on an otherwise identical, polymer-coated drug-eluting stent (DES) platform.



Stents with identical design and biodegradable polymeric coating that elute either rapamycin or paclitaxel over a 2 months time period were utilized. In this pilot trial that included 91 patients, both stent platforms proved safe with no case of death, Q-wave myocardial infarction or stent thrombosis within a 9 months follow-up period. Late-lumen loss was markedly greater in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group (0.96 +/- 0.75 vs. 0.33 +/- 0.46 mm, P < 0.0001). Likewise, the rate of angiographic restenosis was higher in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group [39.0 vs. 12.2%; relative risk (RR) 3.20 (95% confidence interval, 1.29-7.92), P = 0.005]. Concomitantly, the need for target lesion revascularization was higher in the paclitaxel-eluting stent group compared with the rapamycin-eluting stent group [26.7 vs. 8.7%; RR 3.07 (1.07-8.80), P = 0.02].



The results of this clinical trial that is the first to directly compare the performance of paclitaxel and rapamycin on a DES platform otherwise identical in design and polymeric coating imply that rapamycin is more effective for the prevention of coronary restenosis on a DES platform with mid-term drug release and less dependent on release kinetics than paclitaxel. Thus, to ensure efficacy, drug release from a paclitaxel-coating stent platform must be prolonged and well controlled to achieve results that are comparable with the FDA-approved paclitaxel-eluting stent platform.
Dendritic Cell-Based Xenoantigen Vaccination for Prostate Cancer Immunotherapy 1

Many tumor-associated Ags represent tissue differentiation Ags that are poorly immunogenic. Their weak immunogenicity may be due to immune tolerance to self-Ags. Prostatic acid phosphatase (PAP) is just such an Ag that is expressed by both normal and malignant prostate tissue. We have previously demonstrated that PAP can be immunogenic in a rodent model. However, generation of prostate-specific autoimmunity was seen only when a xenogeneic homolog of PAP was used as the immunogen. To explore the potential role of xenoantigen immunization in cancer patients, we performed a phase I clinical trial using dendritic cells pulsed with recombinant mouse PAP as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly vaccinations of xenoantigen-loaded dendritic cells with minimal treatment-associated side effects. All patients developed T cell immunity to mouse PAP following immunization. Eleven of the 21 patients also developed T cell proliferative responses to the homologous self-Ag. These responses were associated with Ag-specific IFNand/or TNFsecretion, but not IL-4, consistent with induction of Th1 immunity. Finally, 6 of 21 patients had clinical stabilization of their previously progressing prostate cancer. All six of these patients developed T cell immunity to human PAP following vaccination. These results demonstrate that xenoantigen immunization can break tolerance to a self-Ag in humans, resulting in a clinically significant antitumor effect.
Continuous subcutaneous glucose monitoring in children with type 1 diabetes.

To determine whether the use of continuous subcutaneous glucose monitoring will help in detecting unrecognized nocturnal hypoglycemia and in lowering hemoglobin A1c (HbA1c) levels (without increasing the risk for severe hypoglycemia) in children with type 1 diabetes.



Eleven children with type 1 diabetes and HbA1c values consistently >8.0% were randomized either to the Continuous Glucose Monitoring System (CGMS) group or to the control group. The CGMS group used 6 3-day sensors within a 30-day period. Both groups self-monitored their blood glucose levels a minimum of 4 times daily. HbA1c levels were measured at the start, at 1-month, and after 3 months of study.



The 5 children using the CGMS had 17 asymptomatic episodes (85%) of glucose levels below 60 mg/dL (3.25 mmol/L) and 3 symptomatic episodes (15%) during the night in the study month. The 6 control children had 4 symptomatic nocturnal low episodes during the month. After the 30-day period of wearing the CGMS, the 5 children had a significantly lower mean HbA1c value compared with their initial value (mean +/- standard error of the mean [SEM] decrease =.36% +/-.07%). The mean decrease for the controls was.2% +/-.2%. After 3 months, 4 of the 5 children who used the CGMS continued to have lower HbA1c values in comparison to their initial values (mean +/- SEM decrease = 1.04% +/-.43%). Three of the 6 control participants also had lower HbA1c values at 3 months (mean +/- SEM decrease for the group =.62% +/-.44%). No severe hypoglycemic events occurred in either the CGMS or the control groups.



In this pilot trial, continuous subcutaneous glucose monitoring was helpful in detecting asymptomatic nocturnal hypoglycemia as well as in lowering HbA1c values without increasing the risk for severe hypoglycemia in children with type 1 diabetes.
Preoperative mapping of cortical language areas in adult brain tumour patients using PET and individual non-normalised SPM analyses

In patients scheduled for the resection of perisylvian brain tumours, knowledge of the cortical topography of language functions is crucial in order to avoid neurological deficits. We investigated the applicability of statistical parametric mapping (SPM) without stereotactic normalisation for individual preoperative language function brain mapping using positron emission tomography (PET). Seven right-handed adult patients with left-sided brain tumours (six frontal and one temporal) underwent 12 oxygen-15 labelled water PET scans during overt verb generation and rest. Individual activation maps were calculated for P<0.005 and P<0.001 without anatomical normalisation and overlaid onto the individuals' magnetic resonance images for preoperative planning. Activations corresponding to Broca's and Wernicke's areas were found in five and six cases, respectively, for P<0.005 and in three and six cases, respectively, for P<0.001. One patient with a glioma located in the classical Broca's area without aphasic symptoms presented an activation of the adjacent inferior frontal cortex and of a right-sided area homologous to Broca's area. Four additional patients with left frontal tumours also presented activations of the right-sided Broca's homologue; two of these showed aphasic symptoms and two only a weak or no activation of Broca's area. Other frequently observed activations included bilaterally the superior temporal gyri, prefrontal cortices, anterior insulae, motor areas and the cerebellum. The middle and inferior temporal gyri were activated predominantly on the left. An SPM group analysis (P<0.05, corrected) in patients with left frontal tumours confirmed the activation pattern shown by the individual analyses. We conclude that SPM analyses without stereotactic normalisation offer a promising alternative for analysing individual preoperative language function brain mapping studies. The observed right frontal activations agree with proposed reorganisation processes, but they may also reflect an unspecific recruitment of the right-sided Broca's homologue in the effort to perform the task.
Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study

To evaluate whether the prevalence of HIV-1 transmitted drug resistance has continued to decline in infections probably acquired within the United Kingdom.



Multicentre observational study.



All UK public laboratories conducting tests for genotypic HIV resistance as a part of routine care.



14,584 patients infected with HIV-1 subtype B virus, who were first tested for resistance before receiving antiretroviral therapy between January 2002 and December 2009.



Prevalence of transmitted drug resistance, defined as one or more resistance mutations from the surveillance list recommended by the World Health Organization.



1654 (11.3%, 95% confidence interval 10.8% to 11.9%) patients had one or more mutations associated with transmitted HIV-1 drug resistance; prevalence was found to decline from 15.5% in 2002 to 9.6% in 2007, followed by a slight increase to 10.9% in 2009 (P=0.21). This later rise was mainly a result of increases in resistance to nucleos(t)ide reverse transcriptase inhibitors (from 5.4% in 2007 to 6.6% in 2009, P=0.24) and protease inhibitors (1.5% to 2.1%, P=0.12). Thymidine analogue mutations, including T215 revertants, remained the most frequent mutations associated with nucleos(t)ide reverse transcriptase inhibitors, despite a considerable fall in stavudine and zidovudine use between 2002 and 2009 (from 29.4% of drug regimens in 2002 to 0.8% in 2009, from 47.9% to 8.8%, respectively).



The previously observed decline in the prevalence of transmitted drug resistance in HIV-1 infections probably acquired in the UK seems to have stabilised. The continued high prevalence of thymidine analogue mutations suggests that the source of this resistance may be increasingly from patients who have not undergone antiretroviral therapy and who harbour resistant viruses. Testing of all newly diagnosed HIV-1 positive people should be continued.
Investigation of Distribution of Heavy Metals between Blood Plasma and Blood Cells

The physiological importance of metals in human organism has been shown by many publications. The toxic doses of metals and their compounds can lead to serious health problems. Different metals present in the composition of blood can form different complexes with many organic compounds and biomolecules which could be found in the body fluids. Depending on the concentration of metals in the parts of body, different metal-ligand equilibriums could be established in the system. These changes could cause changes in global bioprocesses, or different clinical symptoms and metabolic stresses in human organism could occur. The distribution of metals between blood plasma and blood cells could represent an important clinical index. The aim of the present study was to investigate, for the first time to our knowledge, the distribution of heavy metals between blood plasma and cells in the blood samples from the infected by hepatitis C and non-infected patients.
Detailed analysis of proprioception in normal and ACL-deficient knees.

We assessed proprioception using threshold levels for the perception of knee movement at slow angular velocities (0.1 degrees/s to 0.85 degrees/s) in 20 patients with unilateral tears of the anterior cruciate ligament (ACL) and 15 age-related control subjects. Failure to detect movement was also analysed. The threshold levels of detection did not differ between the damaged and undamaged knees in the patients or between the patients and the control group. Failure to appreciate movement, however, was significantly greater in knees with ACL loss compared with the undamaged knees of patients and the control group. Our findings show a proprioceptive deficit in the absence of the ACL. Measurements of threshold levels of detection of passive movement alone are not suitable for the evaluation of proprioceptive loss in ACL deficiency; assessment of failure to appreciate movement is essential.