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"Ladas, G. E"
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Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer
Background
Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented.
Methods
Fifty-six patients between the ages of 5–21 with newly diagnosed leukemia, lymphoma, extracranial solid tumor or medulloblastoma and expected to receive a minimum cumulative dose of 6 mg/m
2
of vincristine over a 30-week period were eligible. Patients’ neurological functioning was monitored every 3 weeks using clinical history, exam, and assessment of motor functioning. Upon identification of neuropathy, patients were randomized to either glutamine (6 g/m
2
per dose twice daily, maximum 10 g/dose) or placebo for a 3-week period followed by 3-week wash out period (Time 3).
Results
Forty-nine patients were fully evaluable and 100 % developed neuropathy per study definitions. No significant differences in demographics or side effects were noted between the randomized groups. The distribution of sensory neuropathy scores between the two groups was statistically significant after the intervention (
p
= 0.022). Children receiving glutamine also rated their quality of life (QoL) as 8.42 points higher on the PedsQL total score than those receiving placebo (
p
= 0.031).
Conclusions
Glutamine supplementation is well tolerated and associated with improvements in sensory function and self-reported overall quality of life. Future studies are warranted to confirm the efficacy of glutamine for the treatment of vincristine-related sensory neuropathy in pediatric cancer patients.
Journal Article
Gains in cognition through combined cognitive and physical training: the role of training dosage and severity of neurocognitive disorder
Physical as well as cognitive training interventions improve specific cognitive functions but effects barely generalize on global cognition. Combined physical and cognitive training may overcome this shortcoming as physical training may facilitate the neuroplastic potential which, in turn, may be guided by cognitive training. This study aimed at investigating the benefits of combined training on global cognition while assessing the effect of training dosage and exploring the role of several potential effect modifiers. In this multi-center study, 322 older adults with or without neurocognitive disorders (NCDs) were allocated to a computerized, game-based, combined physical and cognitive training group (n = 237) or a passive control group (n = 85). Training group participants were allocated to different training dosages ranging from 24 to 110 potential sessions. In a pre-post-test design, global cognition was assessed by averaging standardized performance in working memory, episodic memory and executive function tests. The intervention group increased in global cognition compared to the control group, p = 0.002, Cohen's d = 0.31. Exploratory analysis revealed a trend for less benefits in participants with more severe NCD, p = 0.08 (cognitively healthy: d = 0.54; mild cognitive impairment: d = 0.19; dementia: d = 0.04). In participants without dementia, we found a dose-response effect of the potential number and of the completed number of training sessions on global cognition, p = 0.008 and p = 0.04, respectively. The results indicate that combined physical and cognitive training improves global cognition in a dose-responsive manner but these benefits may be less pronounced in older adults with more severe NCD. The long-lasting impact of combined training on the incidence and trajectory of NCDs in relation to its severity should be assessed in future long-term trials.
Journal Article
Models of care and associated targeted implementation strategies for cancer survivorship support in Europe: a scoping review protocol
IntroductionCancer and its treatments can lead to a wide range of side-effects that can persist long after treatments have ended. Across Europe, survivorship care is traditionally hospital-based specialist-led follow-up, leading to gaps in supportive care. Improved screening, diagnosis and treatment increase survival rates. With more individuals living with, through and beyond cancer, the predominance of the hospital-based specialist model is unsustainable, costly and resource-intensive. An understanding of what alternative Models of Care are available and the barriers and facilitators to their implementation is a first step towards enhancing supportive care across the cancer journey. The aim of this scoping review is to source and synthesise information from studies evaluating patient-oriented models of cancer survivorship supportive care for adults in Europe.Methods and analysisThe scoping review will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses—Scoping Review Extension guidelines and will be guided by a six-stage methodological framework. A search strategy has been developed according to the Population, Concept and Context structure and will be applied to seven databases. A targeted search of grey literature will be completed. All identified records will be screened using predefined eligibility criteria by at least two researchers and undergo full-text review for inclusion. Data pertaining to the conceptualisation, evaluation and implementation of sourced Models of Care will be extracted.Ethics and disseminationAs there is no primary data, ethical approval is not required. This review will be conducted as part of the EU COST Action CA21152—Implementation Network Europe for Cancer Survivorship Care. The protocol and subsequent scoping review will be published in a peer-reviewed journal. The Action involves representatives from most countries across Europe which will assist with the dissemination of the work to key stakeholders.
Journal Article
Keratinocyte growth factor is effective in the prevention of intestinal mucositis in patients with hematological malignancies treated with high-dose chemotherapy and autologous hematopoietic SCT: a video-capsule endoscopy study
Oral and/or intestinal mucositis is a severe complication of hematopoietic SCT. Keratinocyte growth factor (KGF) has proven activity in the prevention of oral mucositis. We examined the efficacy of KGF in the prevention of intestinal mucositis. From January 2006 until December 2007, 35 consecutive patients underwent autologous SCT (auto-SCT) in our institution. A total of 15 consecutive patients who underwent auto-SCT from March 2007 to December 2007 received KGF for the prevention of mucositis and were included in the study group A, whereas 20 consecutive patients treated from January 2006 to March 2007, were included in the historical control group B. Oral and intestinal mucositis were significantly less severe in group A (
P
=0.002 and
P
<0.001, respectively). These results were confirmed with the use of video-capsule endoscopy. Patients in group A had a significantly lower incidence of neutropenic fever (
P
=0.026). Severe intestinal mucositis was significantly associated with a higher incidence of documented infections too (
P
=0.019). KGF is effective in the prevention of intestinal mucositis in patients undergoing auto-SCT. Patients with severe intestinal mucositis run a higher risk to develop infections.
Journal Article
Anatomical and functional impairment of the retina and optic nerve in patients with anorexia nervosa without vision loss
AimThe aim of this cross-sectional study is to evaluate the macular and retinal nerve fibre layer (RNFL) thickness, as well as the electrical activity of the macula in female patients suffering from anorexia nervosa (AN) without visual failure.Material and methods13 female patients (26 eyes) suffering from AN without visual failure and 20 age and sex-matched healthy female controls (40 eyes) were studied. For the measurement of the macula thickness and the electrical activity of the macula, the optical coherence tomography (OCT) and the multifocal electroretinogram were used respectively.ResultsThe visual acuity, as well as the visual fields, the colour vision testing and the dark adaptation test of all patients were normal. However, the mean foveal thickness was 140.04 μm (vs 150.85 in the control group, p=0.005), and the RNFL thickness was limited to 116.42 μm in the superior area (vs 123.15 in the control group, p=0.372) and 121.08 μm in the inferior area (vs 137.6 in the control group, p<0.001) around the optic nerve. Also, the mean P1 response density amplitude of the foveal area was 159.04 nV/deg2 (vs 292.43 in the control group, p<0.0001), and the perifoveal area was 79.04 nV/deg2 (vs 82.63 in the control group, p=0.118).ConclusionThe present study shows that in patients with AN, even without visual failure there is a decrease in macular and RNFL thickness, as well as a decrease in the electrical activity of the macula.
Journal Article
Glass of Water Immediately Increases Gastric pH in Healthy Subjects
Onset of action of antisecretory agents is of pivotal importance for patients with gastroesophageal reflux disease (GERD) treated “on-demand.” Aim To study the acute effect of acid-inhibiting drugs and water administration on gastric pH. Method A cross-over study was performed in 12 H. pylori (-), healthy subjects (6 men; mean age: 26 years). A single oral dose of the following agents was received with a wash-out period between each study: a glass of water (200 ml), antacid, ranitidine, omeprazole, esomeprazole, and rabeprazole. Gastric pH was recorded for 6 h after drug intake. Results Water increased gastric pH >4 in 10/12 subjects after 1 min. The time (median) needed to pH >4 was for: antacid 2 min, ranitidine 50 min, omeprazole 171 min, esomeprazole 151 min, and rabeprazole 175 min. Gastric pH >4 lasted for 3 min after water and for 12 min after antacids; it remained >4 until the end of recording in: 4/12 subjects with ranitidine, 11/12 with rabeprazole, and all with omeprazole and esomeprazole. Conclusion Water and antacid immediately increased gastric pH, while PPIs showed a delayed but prolonged effect compared to ranitidine.
Journal Article
Macular hole surgery with short-acting gas and short-duration face-down positioning
To report on the outcomes of vitrectomy and sulfur hexafluoride (SF(6)) gas tamponade for idiopathic macular holes with 2 days of face-down positioning.
This was a prospective, nonrandomized, observational sequential case-series study on 23 consecutive patients receiving macular hole surgery using 20% SF(6) and advised to stay in a face-down position for 2 days postoperatively (SF(6) group). These patients were compared to 23 consecutive patients who had previously undergone macular hole surgery, had received 14% C(3)F(8), and were advised to maintain a face-down position for 2 days (C(3)F(8) group). Patients in both groups underwent vitrectomy, internal limiting membrane peeling, and fluid gas exchange using either SF(6) or C(3)F(8.) Preoperative and postoperative data included best corrected visual acuity recorded in LogMAR units, slit-lamp biomicroscopy, and optical coherence tomography.
At a 6-month follow-up, macular hole closure was noted in 23/23 eyes (100%) and in 22/23 eyes (96%) in the SF(6) and C(3)F(8) groups, respectively. The improvement in visual acuity (measured through Snellen acuity lines both preoperatively until 6 months postoperatively) was 4.08 ± 2.31 (95% confidence interval [CI]: 3.08-5.08) for the SF(6) group and 2.87 ± 2.30 (95% CI: 1.87-3.86) for the C(3)F(8) group; this difference was not statistically significant (P = 0.06).
Vitrectomy with internal limiting membrane peeling and a short-acting gas tamponade using SF(6) with posture limitation for 2 days may give a high success rate in macular hole surgery.
Journal Article
Use of Sedation for Routine Diagnostic Upper Gastrointestinal Endoscopy: A European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members
Background/Aims: Sedation rates may vary among countries, depending on patients’ and endoscopists’ preferences. The aim of this survey was to investigate the rate of using premedication for routine diagnostic upper gastrointestinal (UGI) endoscopy in endoscopy societies, members of the European Society of Gastrointestinal Endoscopy (ESGE). Methods: We evaluated a multiple-choice questionnaire which was e-mailed to representatives of national endoscopy societies, which are members of the ESGE. The questionnaire had 14 items referring to endoscopy practices in each country and the representatives’ endoscopy units. Results: The response rate was 76% (34/45). In 47% of the countries, less than 25% of patients undergo routine diagnostic UGI endoscopy with conscious sedation. In 62% of the responders’ endoscopy units, patients are not asked their preference for sedation and do not sign a consent form (59%). Common sedatives in use are midazolam (82%), diazepam (38%) or propofol (47%). Monitoring equipment is not available ‘in most of the endoscopy units’ in 46% (13/28) of the countries. Though they were available in 91% of the national representatives’ endoscopy units, they are rarely (21%) used to monitor unsedated routine diagnostic UGI endoscopy. Conclusions: In about 50% of ESGE-related countries, less than 25% of patients are sedated for routine diagnostic UGI endoscopy. Major issues to improve include availability of monitoring equipment and the use of a consent form.
Journal Article
Relationship of Helicobacter pylori cagA status to gastric cell proliferation and apoptosis
Despite the fact that the association of Helicobacter pylori with an increased risk of gastric cancer is well documented, the exact mechanisms of this association have not been elucidated. Our aim was to shed some light on these mechanisms by studying the relationship of H. pylori CagA status to gastric cell proliferation and apoptosis, since both play an important role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fifty patients [32 men, 18 women, median age 39.5 years (range 18-67)], referred for upper gastrointestinal endoscopy, from whom antral biopsies were taken. On biopsy specimens gastritis was estimated by scoring the severity of inflammatory infiltrate, and the presence of atrophy and intestinal metaplasia were also noted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelial apoptotic index (AI) was measured by special staining for apoptosis, and CagA status was determined serologically by immunoblotting the sera of patients against H. pylori antigens. Thirty-eight (76%) of the 50 patients were H. pylori (positive) and 12 (24%) H. pylori (negative). Among the 38 H. pylori(+) patients, 28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the H. pylori CagA(+) and CagA(-) groups, the PI values [median (ranges)] were 5 (4-7) and 3.7 (3.5-5.5), respectively (P < 0.05). In addition the difference in PI between the H. pylori CagA(+) and H. pylori(-) groups was highly significant (P < 0.001). Concerning apoptosis, in the H. pylori CagA(+) and CagA(-) groups, the values for AI were 1 (1-30) and 5.5 (1-35), respectively (P < 0.05). In addition, the difference in AI between the H. pylori CagA(-) and H. pylori(-) groups, was significant (P < 0.05). We conclude that H. pylori CagA(+) strains induce increased gastric cell proliferation, which is not accompanied by a parallel increase in apoptosis. This might explain the increased risk for gastric carcinoma that is associated with infection by H. pylori CagA(+) strains.
Journal Article