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Veys, K. R. P., M. A. Elmonem, M. van Dyck, M. C. Janssen, E. A. M. Cornelissen, K. Hohenfellner, G. Prencipe, L. P. van den Heuvel, and E. Levtchenko, "Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis.", Journal of the American Society of Nephrology : JASN, 2020 Apr 09. Abstract

BACKGROUND: Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis. Because macrophage-mediated inflammation plays an important role in the pathogenesis of cystinosis, biomarkers of macrophage activation could have potential for the therapeutic monitoring of cystinosis.

METHODS: We conducted a 2-year prospective, longitudinal study in which 61 patients with cystinosis who were receiving cysteamine therapy were recruited from three European reference centers. Each regular care visit included measuring four biomarkers of macrophage activation: IL-1, IL-6, IL-18, and chitotriosidase enzyme activity.

RESULTS: A multivariate linear regression analysis of the longitudinal data for 57 analyzable patients found chitotriosidase enzyme activity and IL-6 to be significant independent predictors for white blood cell cystine levels in patients of all ages with cystinosis; a receiver operating characteristic analysis ranked chitotriosidase as superior to IL-6 in distinguishing good from poor therapeutic control (on the basis of white blood cell cystine levels of <2 nmol 1/2 cystine/mg protein or ≥2 nmol 1/2 cystine/mg protein, respectively). Moreover, in patients with at least one extrarenal complication, chitotriosidase significantly correlated with the number of extrarenal complications and was superior to white blood cell cystine levels in predicting the presence of multiple extrarenal complications.

CONCLUSIONS: Chitotriosidase enzyme activity holds promise as a biomarker for use in therapeutic monitoring of nephropathic cystinosis.

Veys, K. R. P., M. A. Elmonem, F. Dhaenens, M. van Dyck, M. M. C. H. Janssen, E. A. M. Cornelissen, K. Hohenfellner, A. Reda, P. Quatresooz, B. van den Heuvel, et al., "Enhanced Intrinsic Skin Aging in Nephropathic Cystinosis Assessed by High-Definition Optical Coherence Tomography.", The Journal of investigative dermatology, 2019 Apr 22. Abstract
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Vialykh, E. A., S. A. Ilarionov, H. M. Abdelrahman, and I. A. Vialykh, "Changes in Amino Acids Content in Humic Acids Repetitively Extracted From Peat And Sod-Podzolic Soils", Canadian Journal of Soil Science, vol. 94, issue 5, pp. 575-583, 2014. AbstractWebsite

Amino acids (AAs) and peptides are thought to be part of humic acids (HAs) but debate whether they are an integral part of the HAs is still going. Humic acids sequentially extracted from peat and sod-podzolic soil were analyzed for their AAs content, elemental composition and by FTIR spectroscopy. Extracted HAs were hydrolyzed in 6 M HCl for 16 h for AAs release, which was detected by capillary electrophoresis system. Alanine, arginine, sum of aspartic acid and asparagine, sum of cysteic acid and cysteine, sum of glutamic acid and glutamine, glycine, histidine, leucine and isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, valine were identified. The total content of hydrolysable AAs in sod-podzol HAs increased by 6.2–8.2% with increasing the extraction cycles while an inverse tendency was observed for AAs released from peat HAs. Moreover, individual AAs expressed as percentages of total AAs were constant values with coefficients of variation lower than 20% for the studied HAs.

Viana, M. V. C., H. Figueiredo, R. Ramos, L. C. Guimarães, F. L. Pereira, F. A. Dorella, S. A. K. Selim, M. Salaheldean, A. Silva, and A. R. Wattam, "Comparative genomic analysis between Corynebacterium pseudotuberculosis strains isolated from buffalo", PloS one, vol. 12, issue 4: Public Library of Science, pp. e0176347, 2017. Abstract
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Viana, M. V. C., H. Figueiredo, R. Ramos, L. C. Guimarães, F. L. Pereira, F. A. Dorella, S. A. K. Selim, M. Salaheldean, A. Silva, and A. R. Wattam, "Comparative genomic analysis between Corynebacterium pseudotuberculosis strains isolated from buffalo", PloS one, vol. 12, issue 4: Public Library of Science, pp. e0176347, 2017. Abstract
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Vichinsky, E., C. C. Hoppe, K. I. Ataga, R. E. Ware, V. Nduba, A. El-Beshlawy, H. Hassab, M. M. Achebe, S. Alkindi, C. R. Brown, et al., "A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease.", The New England journal of medicine, vol. 381, issue 6, pp. 509-519, 2019. Abstract

BACKGROUND: Deoxygenated sickle hemoglobin (HbS) polymerization drives the pathophysiology of sickle cell disease. Therefore, direct inhibition of HbS polymerization has potential to favorably modify disease outcomes. Voxelotor is an HbS polymerization inhibitor.

METHODS: In a multicenter, phase 3, double-blind, randomized, placebo-controlled trial, we compared the efficacy and safety of two dose levels of voxelotor (1500 mg and 900 mg, administered orally once daily) with placebo in persons with sickle cell disease. The primary end point was the percentage of participants who had a hemoglobin response, which was defined as an increase of more than 1.0 g per deciliter from baseline at week 24 in the intention-to-treat analysis.

RESULTS: A total of 274 participants were randomly assigned in a 1:1:1 ratio to receive a once-daily oral dose of 1500 mg of voxelotor, 900 mg of voxelotor, or placebo. Most participants had sickle cell anemia (homozygous hemoglobin S or hemoglobin Sβ-thalassemia), and approximately two thirds were receiving hydroxyurea at baseline. In the intention-to-treat analysis, a significantly higher percentage of participants had a hemoglobin response in the 1500-mg voxelotor group (51%; 95% confidence interval [CI], 41 to 61) than in the placebo group (7%; 95% CI, 1 to 12). Anemia worsened between baseline and week 24 in fewer participants in each voxelotor dose group than in those receiving placebo. At week 24, the 1500-mg voxelotor group had significantly greater reductions from baseline in the indirect bilirubin level and percentage of reticulocytes than the placebo group. The percentage of participants with an adverse event that occurred or worsened during the treatment period was similar across the trial groups. Adverse events of at least grade 3 occurred in 26% of the participants in the 1500-mg voxelotor group, 23% in the 900-mg voxelotor group, and 26% in the placebo group. Most adverse events were not related to the trial drug or placebo, as determined by the investigators.

CONCLUSIONS: In this phase 3 randomized, placebo-controlled trial involving participants with sickle cell disease, voxelotor significantly increased hemoglobin levels and reduced markers of hemolysis. These findings are consistent with inhibition of HbS polymerization and indicate a disease-modifying potential. (Funded by Global Blood Therapeutics; HOPE ClinicalTrials.gov number, NCT03036813.).

Vichinsky, E., A. El-Beshlawy, A. Al Zoebie, A. Kamdem, S. Koussa, T. Chotsampancharoen, A. Bruederle, G. Gilotti, J. Han, and M. Elalfy, "Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST).", Pediatric blood & cancer, vol. 64, issue 9, 2017 Sep. Abstract

BACKGROUND: Children with red blood cell disorders may receive regular transfusions from an early age and consequently accumulate iron. Adequate iron chelation therapy can prevent organ damage and delayed growth/development. Deferasirox is indicated for treatment of pediatric patients with chronic iron overload due to transfusional hemosiderosis; however, fewer than 10% of patients in the registration studies were aged 2 to less than 6 years.

PROCEDURE: Deferasirox, a once-daily oral iron chelator, was evaluated in young pediatric patients with transfusional hemosiderosis during the observational 5-year ENTRUST study. Patients aged 2 to less than 6 years at enrollment received deferasirox according to local prescribing information, with the primary objective of evaluating safety, specifically renal and hepatic function. Serum ferritin was observed as a surrogate efficacy parameter.

RESULTS: In total, 267 patients (mean age 3.2 years) predominantly with β-thalassemia (n = 176, 65.9%) were enrolled. Mean ± standard deviation deferasirox dose was 25.8 ± 6.5 mg/kg per day over a median of 59.9 months. A total of 145 patients (54.3%) completed 5 years' treatment. The proportion of patients with two or more consecutive postbaseline measurements (≥7 days apart) of serum creatinine higher than age-adjusted upper limit of normal (ULN) and alanine aminotransferase more than five times the ULN was 4.4% (95% confidence interval [CI]: 2.1-7.9) and 4.0% (95% CI: 1.8-7.4), respectively. Median serum ferritin decreased from 1,702 ng/ml at baseline to 1,127 ng/ml at 5 years. There were no new safety signals.

CONCLUSIONS: Safety and efficacy of deferasirox in young pediatric patients in this long-term, observational study in everyday clinical practice were consistent with the known deferasirox profile.

Vickery, N., T. Stephens, L. du Toit, D. van Straaten, R. Pearse, A. Torborg, L. Rolt, M. Puchert, G. Martin, and B. Biccard, Understanding the performance of a pan-African intervention to reduce postoperative mortality: a mixed-methods process evaluation of the ASOS-2 trial, , vol. 127, issue 5, pp. 778 - 788, 2021. AbstractWebsite

BackgroundThe African Surgical OutcomeS-2 (ASOS-2) trial tested an enhanced postoperative surveillance intervention to reduce postoperative mortality in Africa. We undertook a concurrent evaluation to understand the process of intervention delivery.
Methods
Mixed-methods process evaluation, including field notes, interviews, and post-trial questionnaire responses. Qualitative analysis used the framework method with subsequent creation of comparative case studies, grouping hospitals by intervention fidelity. A post-trial questionnaire was developed using initial qualitative analyses. Categorical variables were summarised as count (%) and continuous variables as median (inter-quartile range [IQR]). Odds ratios (OR) were used to rank influences by impact on fidelity.
Results
The dataset included eight in-depth case studies, and 96 questionnaire responses (response rate 67%) plus intervention fidelity data for each trial site. Overall, 57% (n=55/96) of hospitals achieved intervention delivery using an inclusive definition of fidelity. Delivery of the ASOS-2 interventions and data collection presented a significant burden to the investigators, outstripping limited resources. The influences most associated with fidelity were: surgical staff enthusiasm for the trial (OR=3.0; 95% confidence interval [CI], 1.3–7.0); nursing management support of the trial (OR=2.6; 95% CI, 1.1–6.5); performance of a dummy run (OR=2.6; 95% CI, 1.1–6.1); nursing colleagues seeing the value of the intervention(s) (OR=2.1; 95% CI, 0.9–5.7); and site investigators' belief in the effectiveness of the intervention (OR=3.2; 95% CI, 1.2–9.4).
Conclusions
ASOS-2 has proved that coordinated interventional research across Africa is possible, but delivering the ASOS-2 interventions was a major challenge for many investigators. Future improvement science efforts must include better planning for intervention delivery, additional support to investigators, and promotion of strong inter-professional teamwork.
Clinical trial registration
ClinicalTrials gov NCT03853824.

Victor, B. C., A. Anbalagan, M. M. Mohamed, B. F. Sloane, and D. Cavallo-Medved, "Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion", Breast Cancer Res, vol. 13, pp. R115, 2011.
Victor, B. C., A. Anbalagan, M. M. Mohamed, B. F. Sloane, and D. Cavallo-Medved, "Inhibition of cathepsin B activity attenuates extracellular matrix degradation and inflammatory breast cancer invasion", Breast Cancer Research, 2011. Abstract

Introduction: Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC.

Victoria, S., H. Amaral, I. Mulamitsi, S. Bhatnagar, H. Moustafa, H. Kartunihardja, F. Sundram, and K. Britton, "CRF on in vivo imaging for infection (sepsis) and inflammation", European Congress Nuclear Medicine, Berlin, 29 Aug- 4 Sept, Submitted.
Vighi, M., P. Gramatica, F. Consolaro, R. Todeschini, F. AylloHn, E. Garcia-Vazquez, J. C. Brodeur, F. Økland, B. Finstad, and G. D. Dixon, Papers to Appear in, , 2001. Abstract
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Vignier, N., G. Esmat, A. Elsharkawy, M. Hassany, P. Bonnard, E. Delarocque-Astagneau, M. Said, R. Raafat, M. El-Hoseiny, A. Fontanet, et al., "Reproducibility of liver stiffness measurements in hepatitis C virus (HCV)-infected patients in Egypt", JOURNAL OF VIRAL HEPATITIS, vol. 18, no. 7, pp. E358-E365, JUL, 2011. Abstract
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Vij, J. K., Y. P. Panarin, S. P. Sreenilayam, M. Alaasar, and C. Tschierske, "Investigation of the heliconical smectic SmCSPFhel phase in achiral bent-​core mesogens derived from 4-​cyanoresorcin", Physical Review Materials, vol. 3, issue 4, pp. 045603, 2019.
Vijay, A., I. Noaman, A. Mahfouz, M. Khawar, H. Khalaf, and A. Elaffandi, "Pancreatico-enteric fistula post pancreatic duct ligation for delayed haemorrhage complicating pancreaticoduodenectomy.", International journal of surgery case reports, vol. 21, pp. 29-31, 2016. Abstract

INTRODUCTION: Pancreatic fistula remains the main cause for postoperative morbidity following pancreaticoduodenectomy. The coincidence of sentinel bleed prior to post pancreatectomy haemorrhage (PPH) and pancreatic fistula is associated with very high mortality.

PRESENTATION OF CASE: We report a case of pancreaticoduodenectomy complicated by postoperative leak and hematemesis. Severe delayed haemorrhage from the pancreatico-jejunostomy necessitated re-laparotomy and complete disconnection of the pancreatic anastomosis. Hemodynamic instability precluded a pancreatectomy or creation of a new anastomosis. A follow up MRI done 3 weeks after the patient's discharge demonstrated a fistulous tract causing a communication between both the pancreatic and biliary systems and the enteric loop.

DISCUSSION: Spontaneous development a pancreatico-enteric fistula despite ligation of the pancreatic duct and complete disconnection of the pancreatic anastomosis has never been reported in literature to date.

CONCLUSION: Pancreatic duct occlusion may be considered over a completion pancreatectomy or revisional pancreatic anastomosis in hemodynamically unstable and challenging cases.

Vijay, A., A. Elaffandi, and H. Khalaf, "Hepatocellular adenoma: An update.", World journal of hepatology, vol. 7, issue 25, pp. 2603-9, 2015. Abstract

Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions.

Vilay, M. A., M. Grio, D. D. DePestel, K. M. Sowinski, L. Gao, M. Heung, N. N. Salama, and B. A. Mueller, "Daptomycin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis", Critical Care Medicine, vol. 39, issue 1, 2011. Abstract

Objective: To investigate daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis to develop dosing recommendations.

Vile, D. J., M. Sharma, M. Fatyga, A. M. Badawi, M. Murphy, C. Ford, and J. Williamson, "A Principal Component Analysis of 3D tissue deformation during external beam radiation therapy for prostate cancer: model validation and random sampling of synthetic images", Mid-Atlantic chapter, American Association of Physics in Medicine, MAC-AAPM: American Association of Physics in Medicine, AAPM, 2011. Abstract
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Vincent, J. L., Aly Makram Habib, C. Verdant, and A. Bruhn, Sepsis diagnosis and management:work in progress, , 2006. sepsis_diagnosis_and_management__work_in_progrss.pdf
Vinuganesh, A., A. Kumar, S. Prakash, M. O. Alotaibi, A. M. Saleh, A. E. Mohammed, G. T. S. Beemster, and H. AbdElgawad, "{Influence of seawater acidification on biochemical composition and oxidative status of green algae Ulva compressa}", Science of the Total Environment, vol. 806: Elsevier B.V., pp. 150445, 2022. AbstractWebsite

The sequestration of elevated atmospheric CO2 levels in seawater results in increasing acidification of oceans and it is unclear what the consequences of this will be on seaweed ecophysiology and ecological services they provide in the coastal ecosystem. In the present study, we examined the physiological and biochemical response of intertidal green seaweed Ulva compressa to elevated pCO2 induced acidification. The green seaweed was exposed to control (pH 8.1) and acidified (pH 7.7) conditions for 2 weeks following which net primary productivity, pigment content, oxidative status and antioxidant enzymes, primary and secondary metabolites, and mineral content were assessed. We observed an increase in primary productivity of the acidified samples, which was associated with increased levels of photosynthetic pigments. Consequently, primary metabolites levels were increased in the thalli grown under lowered pH conditions. There was also richness in various minerals and polyunsaturated fatty acids, indicating that the low pH elevated the nutritional quality of U. compressa. We found that low pH reduced malondialdehyde (MDA) content, suggesting reduced oxidative stress. Consistently we found reduced total antioxidant capacity and a general reduction in the majority of enzymatic and non-enzymatic antioxidants in the thalli grown under acidified conditions. Our results indicate that U. compressa will benefit from seawater acidification by improving productivity. Biochemical changes will affect its nutritional qualities, which may impact the food chain/food web under future acidified ocean conditions.

Viscardi, R. M., A. A. Othman, H. E. Hassan, N. D. Eddington, E. Abebe, M. L. Terrin, D. A. Kaufman, and K. B. Waites, "Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.", Antimicrobial agents and chemotherapy, vol. 57, issue 5, pp. 2127-33, 2013 May. AbstractWebsite

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial clearance, but the effect on BPD remains to be determined.

Vishwanatha, T. M., B. Giepmans, S. K. Goda, and A. Dömling, "Tubulysin Synthesis Featuring Stereoselective Catalysis and Highly Convergent Multicomponent Assembly.", Organic letters, 2020. Abstract

A concise and modular total synthesis of the highly potent N-desacetoxytubulysin H () has been accomplished in 18 steps in an overall yield of up to 30%. Our work highlights the complexity-augmenting and route-shortening power of diastereoselective multicomponent reaction (MCR) as well as the role of bulky ligands to perfectly control both the regioselective and diastereoselective synthesis of tubuphenylalanine in just two steps. The total synthesis not only provides an operationally simple and step economy but will also stimulate major advances in the development of new tubulysin analogues.

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