Publications by authors named "Mohamed F Ibrahim"

35 Publications

Clinico-Radiological Correlation in 26 Egyptian Children with Glutaric Acidemia Type 1.

Neuropediatrics 2021 Feb 23. Epub 2021 Feb 23.

Department of Pediatrics, Faculty of Medicine, Sohag University, Sohag, Egypt.

Background:  Glutaric acidemia type 1 (GA1) is an inherited neurometabolic disease with significant morbidity. However, neuro-radiological correlation is not completely understood.

Objective:  The study aimed to characterize the neuroimaging findings and their association with neurological phenotype in GA1 children.

Methods:  Twenty-six Egyptian children (median age = 12 months) diagnosed with GA1 underwent clinical evaluation and brain magnetic resonance imaging (MRI). We objectively assessed the severity of neurological phenotype at the time of MRI using movement disorder (MD) and morbidity scores. Evaluation of brain MRI abnormalities followed a systematic and region-specific scoring approach. Brain MRI findings and scores were correlated with MD and morbidity scores, disease onset, and presence of seizures.

Results:  Fifteen (57.7%) cases had insidious onset, eight (30.8%) manifested acute onset, whereas three (11.5%) were asymptomatic. Ten (38.5%) cases had seizures, five of which had no acute encephalopathic crisis. Putamen and caudate abnormalities (found in all acute onset, 93.3 and 73.3% of insidious onset, and one of three asymptomatic cases) were significantly related to MD ( = 0.007 and 0.013) and morbidity ( = 0.005 and 0.003) scores. Globus pallidus abnormalities (50% of acute onset, 46.7% of insidious onset, and one of three of asymptomatic cases) were significantly associated with morbidity score ( = 0.023). Other MRI brain abnormalities as well as gray and white matter score showed no significant association with neurological phenotype. Younger age at onset, acute onset, and seizures were significantly associated with worse neurological manifestations.

Conclusion:  Patients with GA1 manifest characteristic and region-specific brain MRI abnormalities, but only striatal affection appears to correlate with neurological phenotype.
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http://dx.doi.org/10.1055/s-0040-1722681DOI Listing
February 2021

Exogenous γ-aminobutyric acid (GABA)-induced signaling events and field performance associated with mitigation of drought stress in L.

Plant Signal Behav 2021 Feb 23;16(2):1853384. Epub 2020 Dec 23.

Department of Agricultural Botany, Faculty of Agriculture, Ain Shams University , Cairo, Egypt.

Not much information is available to substantiate the possible role of γ -aminobutyric acid (GABA) signaling in mitigating water-deficit stress in snap bean ( L.) plants under semiarid conditions. Present work aims to investigate the role of exogenous GABA (foliar application; 0.5, 1 and 2 mM) in amelioration of drought stress and improvement of field performance on snap bean plants raised under two drip irrigation regimes (100% and 70% of water requirements). Water stress led to significant reduction in plant growth, leaf relative water content (RWC), cell membrane stability index (CMSI), nutrient uptake (N, P, K, Ca, Fe and Zn), pod yield and its content from protein and total soluble solids (TSS). Meanwhile, lipid peroxidation (malondialdehyde content- MDA), osmolyte content (free amino acids- FAA, proline, soluble sugars) antioxidative defense (activity of superoxide dismutase- SOD, catalase- CAT, peroxidase- POX and ascorbate peroxidase- APX) and the pod fiber content exhibited significantly increase due to water stress. Exogenous GABA application (especially at 2 mM) revealed partial normalization of the effects of drought stress in snap bean plants. GABA-induced mitigation of drought stress was manifested by improvement in growth, water status, membrane integrity, osmotic adjustment, antioxidant defense and nutrient acquisition. Furthermore, GABA application during water stress in snap bean plants resulted in improvement of field performance being manifested by increased pod yield and its quality attributes. To sum up, exogenous GABA appears to function as an effective priming molecule to alleviate drought stress in snap bean plants under semiarid conditions.
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http://dx.doi.org/10.1080/15592324.2020.1853384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849733PMC
February 2021

Enhanced full-thickness wound healing via extract delivery based on a chitosan/gelatin dressing incorporating microemulsion.

Drug Dev Ind Pharm 2021 Feb 4;47(2):215-224. Epub 2021 Jan 4.

Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.

There are many synthetic drugs in literature have been utilized in healing of the wounds although the natural product specially antioxidants can offer similar if not better biological activity in that regard. Genus Sophora is well known to contain flavonoids and phenolic compounds which have antioxidant and inflammatory effects. So, the aim of the current study was to develop and evaluate chitosan/gelatin based extract-loaded microemulsion as wound dressing. extract (SGE) contained 16 major compounds which have reasonable antioxidant activity. The developed microemulsion showed that Tween 80 produced significant ( < 0.05) lower particle size than Pluronic F127 at the same SGE concentration whereas high concentration of extract results in large particle size. Thermodynamic stability studies showed that using higher concentration of the extract produced less stable formulations. The selected formulation was impregnated in the dressing base (chitosan/gelatin; 2:1 w/w ratio) which exhibited more water absorption. evaluation revealed that the dressing displayed superior wound repair compared to the control in terms histological examination and determination of alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA). Thus, SGE-loaded microemulsion-impregnated gelatin/chitosan could be a potential candidate for the wound healing.
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http://dx.doi.org/10.1080/03639045.2020.1863420DOI Listing
February 2021

Influence of Polyethylene Glycol on Leaf Anatomy, Stomatal Behavior, Water Loss, and Some Physiological Traits of Date Palm Plantlets Grown and .

Plants (Basel) 2020 Oct 26;9(11). Epub 2020 Oct 26.

Department of Agricultural Botany, Faculty of Agriculture, Ain Shams University, Cairo 11566, Egypt.

Few reports explain the mechanism of PEG action on stomatal behavior and anatomical structure and analyze the photosynthetic pigments of date palm plantlets for better tolerance to exposure. The main challenge for micropropagation of date palm techniques remains restricted to high survival rates and vigorous growth after transplantation. hardening is induced by Polyethylene glycol PEG (0.0, 10, 20, 30 g L) for 4 weeks. Leaf anatomy, stomatal behavior, water loss %, photosynthetic pigments, and reducing sugars were examined in date palm plantlets ( L.) cv. (Sewi) after 4 weeks from PEG treatment and after 4 weeks from transplanting to the greenhouse. Leaf anatomy and the surface ultrastructure of untreated leaves showed a thin cuticle layer, wide opened malfunctioning stomata, and abnormal leaf anatomy. Furthermore, addition of PEG resulted in increasing cuticle thickness, epicuticular wax depositions, and plastids density, improving the stomatal ability to close and decreasing the stomatal aperture length while reducing the substomatal chambers and intercellular spaces in the mesophyll. As a result, a significant reduction in water loss % was observed in both and PEG treated leaves as compared to untreated ones, which exhibited rapid wilting when exposed to low humidity for 4 h. PEG application significantly increased Chlorophylls a, b and carotenoids concentrations, especially 10, 20 g L treatments, which were sequentially reflected in increasing the reducing sugar concentration. However, leaves of plantlets treated with PEG at 30 g L became yellow and had necrosis ends with death. hardening by 20 g L PEG increased the survival rate of plantlets to 90% after transfer compared to 63% recorded for the untreated plantlets. Therefore, this application provides normal date palm plantlets developed faster and enhances survival after transfer.
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http://dx.doi.org/10.3390/plants9111440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693573PMC
October 2020

Melatonin Counteracts Drought Induced Oxidative Damage and Stimulates Growth, Productivity and Fruit Quality Properties of Tomato Plants.

Plants (Basel) 2020 Sep 28;9(10). Epub 2020 Sep 28.

Department of Horticulture, Faculty of Agriculture, Ain Shams University, 11566 Cairo, Egypt.

Melatonin "-Acetyl-5-methoxytryptamine" (MT) has recently been considered as a new plant growth regulator with multiple physiological functions. Although many previous studies have confirmed that exogenous applied-MT can alleviate the deleterious effects of drought stress in many plant species, most of these studies were exclusive on seeds, seedlings, and young plants for a short period of their life cycles. Therefore, the knowledge of using MT as a potential promising agricultural foliar application to improve crop productivity and quality is still insufficient under adverse open field conditions. In this study, we investigated the effect of MT as a foliar application at 0, 20, and 40 ppm on tomato plants that were grown in the open field under the long term of optimal and deficit irrigation conditions. The results indicated that exogenous MT significantly enhanced plant growth, chlorophyll and activities of antioxidant enzymes, including ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POX). This improvement was associated with a marked reduction in proline and soluble sugars. In addition, applied-MT worked as a protective agent against oxidative damage by reducing the cellular content of toxic substances such as HO and malondialdehyde (MDA). Similarly, MT-treated plants showed greater total fruit yield with improving its quality attributes like total soluble solids (TSS), ascorbic acid, and lycopene. Generally, the highest significant fruit yield either under well-watered (13.7%) or water deficit (37.4%) conditions was achieved by the treatment of 20 ppm MT. These results indicate that exogenous MT played an essential role in enhancing tomato tolerance to deficit irrigation and could be recommended as a promising agricultural treatment under such conditions.
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http://dx.doi.org/10.3390/plants9101276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601691PMC
September 2020

Combined targeting EGFR and SRC as a potential novel therapeutic approach for the treatment of triple negative breast cancer.

Ther Adv Med Oncol 2020 28;12:1758835919897546. Epub 2020 Jan 28.

National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.

Background: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. Epidermal growth factor receptor (EGFR) has been shown to be over-expressed in TNBC and represents a rational treatment target.

Methods: We examined single agent and combination effects for afatinib and dasatinib in TNBC. We then determined IC and combination index values using Calcusyn. Functional analysis of single and combination treatments was performed using reverse phase protein array and cell cycle analysis. Finally, we determined the anticancer effects of the combination .

Results: A total of 14 TNBC cell lines responded to afatinib with IC values ranging from 0.008 to 5.0 µM. Three cell lines, belonging to the basal-like subtype of TNBC, were sensitive to afatinib. The addition of afatinib enhanced response to the five other targeted therapies in HCC1937 and HDQP1 cells. The combination of afatinib with dasatinib caused the greatest growth inhibition in both cell lines. The afatinib/dasatinib combination was synergistic and/or additive in 13/14 TNBC cell lines. Combined afatinib/dasatinib treatment induced G1 cell cycle arrest. Reverse phase protein array results showed the afatinib/dasatinib combination resulted in efficient inhibition of both pERK(T202/T204) and pAkt(S473) signalling in BT20 cells, which was associated with the greatest antiproliferative effects. High baseline levels of pSrc(Y416) and pMAPK(p38) correlated with sensitivity to afatinib, whereas low levels of B-cell lymphoma 2 (Bcl2) and mammalian target of rapamycin (mTOR) correlated with synergistic growth inhibition by combined afatinib and dasatinib treatment. , the combination treatment inhibited tumour growth in a HCC1806 xenograft model.

Conclusions: We demonstrate that afatinib combined with dasatinib has potential clinical activity in TNBC but warrants further preclinical investigation.
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http://dx.doi.org/10.1177/1758835919897546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987485PMC
January 2020

Impact of nanostructured lipid carriers on dapsone delivery to the skin: in vitro and in vivo studies.

Int J Pharm 2019 Dec 9;572:118781. Epub 2019 Nov 9.

Department of Pharmaceutics and Ind. Pharmacy, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

The main objective of this study was to develop, characterize and evaluate the potential use of dapsone-loaded nanostructured lipid carriers (NLCs) as a topical treatment for acne. Differently charged NLC formulations were successfully prepared using an emulsification/sonication method. The particle sizes ranged from 106.2 ± 5.6 nm to 151.3 ± 7.4 nm, and the NLCs possessed the predicted surface charges, depending on the emulsifier used (Tween 80, Transcutol P, or cetyltrimethylammonium bromide). The entrapment efficiencies ranged from 76.5 ± 3.8% to 91.1 ± 3.9%. Selected formulations were assessed for possible interactions, in vitro release, ex vivo skin permeation, pharmacological efficacy and safety compared with a hydroalcoholic solution. Dapsone was embedded in the lipid matrix of NLCs and behaved as controlled release system with a good occlusive effect. Dapsone-loaded cationic NLC formulation enhanced the skin permeation of dapsone, increase the amount of dapsone retained in the skin in controlled manner, and improved the anti-rosacea activity. Based on these encouraging results, cationic NLC represents a promising carrier for the safe topical delivery of dapsone.
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http://dx.doi.org/10.1016/j.ijpharm.2019.118781DOI Listing
December 2019

Diagnostic value of the International Ovarian Tumor Analysis (IOTA) simple rules versus pattern recognition to differentiate between malignant and benign ovarian masses.

Int J Gynaecol Obstet 2019 Dec 26;147(3):344-349. Epub 2019 Sep 26.

Department of Obstetrics and Gynecology, Cairo University, Giza, Egypt.

Objective: To compare the efficacy of the International Ovarian Tumor Analysis (IOTA) simple rules versus pattern recognition to differentiate between benign and malignant ovarian masses.

Methods: A prospective cross-sectional study conducted at Kasr El Aini Hospital, Cairo, between April 2016 and October 2018 of 396 women with ovarian masses measuring more than 5 cm who were candidates for surgery. All patients underwent two-dimensional transvaginal sonography: level 2 with IOTA simple rules followed by level 3 with pattern recognition. Patients subsequently underwent ovarian cystectomy or oophorectomy and the specimens were examined histopathologically. Accuracy was measured by comparing sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.

Results: IOTA simple rules specified 44/50 cases as malignant and 220/242 as benign (sensitivity and specificity of 88.0% and 90.9%, respectively). Pattern recognition identified 83/94 cases as malignant and 281/302 as benign (sensitivity and specificity of 88.3% and 92.7%, respectively). No statistically significant difference in accuracy was found between the two methods.

Conclusion: IOTA simple rules are an effective tool for detecting ovarian malignancy when performed by nonexpert sonographers. When results are inconclusive, pattern recognition should be performed additionally by an expert sonographer.

Clinical Trials Registration: NCT02800031.
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http://dx.doi.org/10.1002/ijgo.12970DOI Listing
December 2019

Primary Febrile Neutropenia Prophylaxis for Patients Who Receive FEC-D Chemotherapy for Breast Cancer: A Systematic Review.

J Glob Oncol 2018 09 21;4:1-8. Epub 2017 Apr 21.

Ricardo Fernandes, Mohamed F.K. Ibrahim, Shaan Dudani, Kirstin Perdrizet, Habeeb Majeed, and Risa Shorr, The Ottawa Hospital; Ricardo Fernandes, Shaan Dudani, Kirstin Perdrizet, Habeeb Majeed, Brian Hutton, Dean Fergusson, and Mark Clemons, University of Ottawa; Sasha Mazzarello, Carol Stober, Lisa Vandermeer, Brian Hutton, Dean Fergusson, and Mark Clemons, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; and Bishal Gyawali, Nobel Hospital, Sinamangal, Kathmandu, Nepal.

Purpose: Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was therefore performed.

Methods: Embase, Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, and conference proceedings were searched from 1946 to April 2016 for trials that reported the effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures were incidence of FN; treatment-related hospitalizations; chemotherapy dose delays, reductions, and discontinuations; and adverse events from prophylaxis.

Results: Of 2,205 identified citations, eight studies (n = 1,250) met our eligibility criteria. Three additional studies (n = 293) were identified from a prior systematic review. Three randomized controlled trials (n = 576), one phase IV single-arm trial (n = 69), one prospective observational study (n = 37), and six retrospective studies (n = 861) were identified. Agents investigated were pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The heterogeneity of studies meant that a narrative synthesis of results was performed. Median FN rates for patients who received FEC-D with and without primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and 23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis, FN was more common during docetaxel than during FEC. Data from six studies showed a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and 19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN. Toxicity from prophylaxis itself was rarely reported.

Conclusion: Primary FN prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity of prospective data makes optimal recommendations about the choice and timing of prophylaxis challenging.
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http://dx.doi.org/10.1200/JGO.2016.008540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180804PMC
September 2018

Motor and Cerebellar Architectural Abnormalities during the Early Progression of Ataxia in a Mouse Model of SCA1 and How Early Prevention Leads to a Better Outcome Later in Life.

Front Cell Neurosci 2017 20;11:292. Epub 2017 Sep 20.

Department of Physiology, School of Biomedical Sciences, Brain Health Research Centre, Brain Research New Zealand, University of OtagoDunedin, New Zealand.

Exposing developing cerebellar Purkinje neurons (PNs) to mutant Ataxin1 (ATXN1) in 82Q spinocerebellar ataxia type 1 (SCA1) mice disrupts motor behavior and cerebellar climbing fiber (CF) architecture from as early as 4 weeks of age. In contrast, if mutant ATXN1 expression is silenced until after cerebellar development is complete, then its impact on motor behavior and cerebellar architecture is greatly reduced. Under these conditions even 6 month old SCA1 mice exhibit largely intact motor behavior and molecular layer (ML) and CF architecture but show a modest reduction in PN soma area as a first sign of cerebellar disruption. Our results contrast the sensitivity of the developing cerebellum and remarkable resilience of the adult cerebellum to mutant ATXN1 and imply that SCA1 in this mouse model is both a developmental and neurodegenerative disorder.
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http://dx.doi.org/10.3389/fncel.2017.00292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611386PMC
September 2017

Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: a systematic review.

Breast Cancer Res Treat 2017 01 25;161(1):1-10. Epub 2016 Oct 25.

Department of Medicine, Division of Medical Oncology, The Ottawa Hospital Cancer Centre and University of Ottawa, 501 Smyth Road, Box 912, Ottawa, ON, K1H 8L6, Canada.

Background: Due to the high rate of febrile neutropenia (FN) with docetaxel-cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address this knowledge gap.

Methods: Embase, Ovid Medline, Pubmed, the Cochrane database of systematic reviews, and Cochrane register of controlled trials were searched from 1946 to April 2016 for studies evaluating primary prophylactic FN treatments in breast cancer patients receiving DC chemotherapy. Outcome measures evaluated included: incidence of FN and treatment-related hospitalizations, chemotherapy dose reduction/delays/discontinuations, and adverse events. Screening and data collection were performed by two independent reviewers.

Results: Of 2105 identified records, 7 studies (n = 2535) met the pre-specified eligibility criteria. Seven additional studies (n = 621) were identified from prior systematic reviews. There were 3 randomized controlled trials (RCTs) (n = 2256) and 11 retrospective studies (n = 900). Study sample sizes ranged from 30 to 982 patients (median 99.5), evaluating pegfilgrastim (n = 1274), filgrastim (n = 1758), and oral ciprofloxacin (n = 108). Given the heterogeneity of patients and study design, a narrative synthesis of results was performed. Median FN rates with and without primary prophylaxis were 6.6 % (IQR 3.9-10.6 %) and 31.3 % (IQR 25-33 %), respectively. No FN-related deaths were reported. No RCT directly compared G-CSF with antibiotic interventions.

Conclusions: Primary FN prophylaxis reduces the incidence of FN. Despite considerable cost and toxicity differences between G-CSF and antibiotics, there is insufficient data to make a recommendation of one strategy over another.
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http://dx.doi.org/10.1007/s10549-016-4028-0DOI Listing
January 2017

Metallurgical Parameters Controlling the Eutectic Silicon Charateristics in Be-Treated Al-Si-Mg Alloys.

Materials (Basel) 2016 Jan 27;9(2). Epub 2016 Jan 27.

Département des Sciences appliquées, Université du Québec à Chicoutimi, Chicoutimi, QC G7H 2B1, Canada.

The present work was carried out on Al-7%Si-0.4%Mg-X alloy (where X = Mg, Fe, Sr or Be), where the effect of solidification rate on the eutectic silicon characteristics was investigated. Two solidification rates corresponding to dendrite arm spacings (DAS) of 24 and 65 μm were employed. Samples with 24 μm DAS were solution heat-treated at 540 °C for 5 and 12 h prior to quenching in warm water at 65 °C. Eutectic Si particle charateristics were measured using an image analyzer. The results show that the addition of 0.05% Be leads to partial modification of the Si particles. Full modification was only obtained when Sr was added in an amount of 150-200 ppm, depending on the applied solidification rate. Increasing the amount of Mg to 0.8% in Sr-modified alloys leads to a reduction in the effectiveness of Sr as the main modifier. Similar observations were made when the Fe content was increased in Be-treated alloys due to the Be-Fe interaction. Over-modification results in the precipitation of hard Sr-rich particles, mainly Al₄SrSi₂, whereas overheating causes incipient melting of the Al-Cu eutectic and hence the surrounding matrix. Both factors lead to a deterioration in the alloy mechanical properties. Furthermore, the presence of long, acicular Si particles accelerates the occurrence of fracture and, as a result, yields poor ductility. In low iron (less than 0.1 wt%) Al-Si-Mg alloys, the mechanical properties in the as cast, as well as heat treated conditions, are mainly controlled by the eutectic Si charatersitics. Increasing the iron content and, hence, the volume fraction of Fe-based intermetallics leads to a complex fracture mode.
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http://dx.doi.org/10.3390/ma9020078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456500PMC
January 2016

Treatment choices for patients with invasive lobular breast cancer: a doctor survey.

J Eval Clin Pract 2015 Aug 9;21(4):740-8. Epub 2015 Jun 9.

The Ottawa Hospital Cancer Center, University of Ottawa, Ottawa, Ontario, Canada.

Rationale, Aims And Objectives: Invasive lobular breast cancer (ILC) has distinct features that present challenges for management. We surveyed doctors regarding management approaches, opinions on quality of evidence supporting their practice, and future research needs.

Methods: An online questionnaire was developed and circulated to breast cancer surgical, radiation and medical oncologists.

Results: The questionnaire was completed by 88/428 doctors (20.6%); 22/56 (39.3%) surgeons, 21/64 (32.8%) radiation oncologists and 45/308 (14.6%) medical oncologists. The majority (65%) of surgeons were comfortable treating ILC patients using the same surgical management as patients with invasive ductal cancers (IDC). Furthermore, 25% would perform a similar surgery but would obtain larger gross margins. There was equipoise for radiation oncologists regarding whether or not ILC was an independent risk factor for local-regional recurrence after either breast-conserving surgery or mastectomy. Of those radiation oncologists who believe ILC is an independent risk factor for recurrence after mastectomy, 44.4% would offer radiation in the absence of usual indications. Medical oncologists approached systemic therapy for ILC patients similarly to those with comparable IDCs. Areas identified as most controversial and requiring future research were preoperative magnetic resonance imaging, radiotherapy post-mastectomy and the responsiveness of ILC to adjuvant chemotherapy compared with endocrine therapy.

Conclusions: There is a variation in doctors' beliefs, management and opinions regarding the quality of evidence for the management of ILC. Clinical trials specifically assessing the management of ILC are required to guide clinical practice.
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http://dx.doi.org/10.1111/jep.12379DOI Listing
August 2015

Hybrid Approach to Repair Type A Aortic Dissection: Combined Endovascular Superior Mesenteric Artery Stenting and Bentall Procedure.

Aorta (Stamford) 2014 Aug 1;2(4):156-60. Epub 2014 Aug 1.

Adult Cardiac Surgery Department, Prince Salman Heart Center, King Fahad Medical City, Riyadh, Saudi Arabia.

A Stanford Type A aortic dissection is a life-threatening surgical emergency that requires emergent surgery. The mortality after repair is high especially if the aortic dissection is complicated by visceral or peripheral malperfusion. We describe a case of a male patient who presented with an aortic dissection involving the ascending aorta, aortic arch, descending thoracic aorta, and the abdominal aorta down to the iliac bifurcation. The dissection also involved the visceral and renal arteries with evidence of superior mesenteric artery (SMA) occlusion. Successful outcome was achieved by endovascular stenting of the patient's SMA, followed by a Bentall procedure. To the best of our knowledge this is the first case report in the English literature of SMA stenting followed by a Bentall procedure to treat acute Type A aortic dissection complicated by SMA occlusion.
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http://dx.doi.org/10.12945/j.aorta.2014.14-014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682729PMC
August 2014

Engineering erythrocytes as a novel carrier for the targeted delivery of the anticancer drug paclitaxel.

Saudi Pharm J 2014 Jul 7;22(3):223-30. Epub 2013 Jan 7.

Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia ; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.

Paclitaxel (PTX) is formulated in a mixture of Cremophor EL and dehydrated alcohol. The intravenous administration of this formula is associated with a risk of infection and hypersensitivity reactions. The presence of Cremophor EL as a pharmaceutical vehicle contributes to these effects. Therefore, in this study, we used human erythrocytes, instead of Cremophor, as a pharmaceutical vehicle. PTX was loaded into erythrocytes using the preswelling method. Analysis of the obtained data indicates that 148.8 μg of PTX was loaded/mL erythrocytes, with an entrapment efficiency of 46.36% and a cell recovery of 75.94%. Furthermore, we observed a significant increase in the mean cell volume values of the erythrocytes, whereas both the mean cell hemoglobin and the mean cell hemoglobin concentration decreased following the loading of PTX. The turbulence fragility index values for unloaded, sham-loaded and PTX-loaded erythrocytes were 3, 2, and 1 h, respectively. Additionally, the erythrocyte glutathione level decreased after PTX loading, whereas lipid peroxidation and protein oxidation increased. The release of PTX from loaded erythrocytes followed first-order kinetics, and about 81% of the loaded drug was released into the plasma after 48 h. The results of the present study revealed that PTX was loaded successfully into human erythrocytes with acceptable loading parameters and with some oxidative modification to the erythrocytes.
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http://dx.doi.org/10.1016/j.jsps.2013.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4099562PMC
July 2014

Obstructive bioprosthetic mitral valve thrombus: management options?

Asian Cardiovasc Thorac Ann 2014 Oct 18;22(8):975-8. Epub 2013 Oct 18.

Cardiac Surgery Department, Prince Salman Heart Center, King Fahad Medical City, Riyadh, Saudi Arabia.

Bioprosthetic valve thrombosis is an extremely rare event, therefore, long-term anticoagulation can be avoided. There is limited experience in the diagnosis and treatment of such a situation. We present the case of a patient with a porcine mitral bioprosthesis who presented with acute pulmonary edema, likely secondary to obstructive valve thrombosis. A favorable outcome was observed after conservative anticoagulant treatment.
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http://dx.doi.org/10.1177/0218492313491582DOI Listing
October 2014

Coronary fistula between the left anterior descending coronary artery and the pulmonary artery: Two case reports.

J Saudi Heart Assoc 2012 Oct 10;24(4):253-6. Epub 2012 Aug 10.

Cardiac Surgery Department, Prince Salman Heart Center, King Fahad Medical City, Riyadh.

Coronary artery fistulae are rare congenital or acquired connections between the coronary vessels and the cardiac chambers or other vascular structures. We present two consecutive cases of coronary fistulae between the proximal left anterior descending artery (LAD) and the main pulmonary artery. Both cases where admitted with history of acute coronary syndromes and had multivessel coronary disease along with coronary pulmonary fistulae. The two cases were managed by coronary artery bypass grafting (CABG) and repair of the fistulae.
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http://dx.doi.org/10.1016/j.jsha.2012.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809472PMC
October 2012

Mycotic pseudoaneurysm of the proximal saphenous vein graft.

J Card Surg 2013 Mar 24;28(2):148-9. Epub 2013 Jan 24.

Department of Adult Cardiology, Prince Salman Heart Center, King Fahad Medical City, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1111/jocs.12067DOI Listing
March 2013

Erythrocyte-mediated delivery of pravastatin: in vitro study of effect of hypotonic lysis on biochemical parameters and loading efficiency.

Arch Pharm Res 2012 Aug 1;35(8):1431-9. Epub 2012 Sep 1.

Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Exposure of erythrocytes to hypotonic lysis creates pores in the cell membrane, through which pravastatin can enter and become trapped, after resealing them with a suitable buffer. We investigated the effects of tonicity, incubation time and drug concentration on drug loading into erythrocytes. Furthermore, we investigate the effects of pravastatin on erythrocyte oxidative stress markers and osmotic fragility behavior. Encapsulation was achieved using buffer solutions of different tonicities (0.5, 0.6 and 0.7% NaCl) and different drug concentrations (2, 4, 8 and 10 mg/mL) for a range of incubation times (15, 30, 60 and 120 min). The results demonstrated that controlled hypotonic lysis could entrap pravastatin in human erythrocytes, with acceptable loading parameters. The highest loading (34%) was achieved at 0.6% NaCl and 10 mg/mL pravastatin for 60 min incubation. At this pravastatin concentration, oxidative stress markers were similar to those seen in controls, and fragility and hematological parameters were unaffected in drug-loaded erythrocytes. These results indicate that the loading process and pravastatin concentration had no deleterious effects on the structure of pravastatin-loaded erythrocytes, suggesting that they may therefore have a similar life span to normal cells. Pravastatin-loaded erythrocytes may thus provide an effective extended-release-delivery system for pravastatin.
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http://dx.doi.org/10.1007/s12272-012-0813-4DOI Listing
August 2012

Right pulmonary artery compression by ascending aortic aneurysm.

J Saudi Heart Assoc 2011 Jul 22;23(3):159. Epub 2011 Jan 22.

Cardiac Surgery Department, Prince Salman Heart Center, King Fahad Medical City, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1016/j.jsha.2011.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3801135PMC
July 2011

Characterization of human erythrocytes as potential carrier for pravastatin: an in vitro study.

Int J Med Sci 2011 Mar 11;8(3):222-30. Epub 2011 Mar 11.

Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.

Drug delivery systems including chemical, physical and biological agents that enhance the bioavailability, improve pharmacokinetics and reduce toxicities of the drugs. Carrier erythrocytes are one of the most promising biological drug delivery systems investigated in recent decades. The bioavailability of statin drugs is low due the effects of P-glycoprotein in the gastro-intestinal tract as well as the first-pass metabolism. Therefore in this work we study the effect of time, temperature as well as concentration on the loading of pravastatin in human erythrocytes to be using them as systemic sustained release delivery system for this drug. After the loading process is performed the carriers' erythrocytes were physically and cellulary characterized. Also, the in vitro release of pravastatin from carrier erythrocytes was studied over time interval. Our results revealed that, human erythrocytes have been successfully loaded with pravastatin using endocytosis method either at 25(o)C or at 37(o)C. The loaded amount at 10 mg/ml is 0.32 mg/0.1 ml and 0.69 mg/0.1 ml. Entrapment efficiency is 34% and 94% at 25(o)C and 37(o)C respectively at drug concentration 4 mg/ml. Moreover the percent of cells recovery is 87-93%. Hematological parameters and osmotic fragility behavior of pravastatin loaded erythrocytes were similar that of native erythrocytes. Scanning electron microscopy demonstrated that the pravastatin loaded cells has no change in the morphology. Pravastatin releasing from carrier cell was 83% after 23 hours in phosphate buffer saline and decreased to 72% by treatment of carrier cells with glutaraldehyde. The releasing pattern of the drug from loaded erythrocytes obeyed first order kinetics. It concluded that pravastatin is successfully entrapped into erythrocytes with acceptable loading parameters and moderate morphological changes, this suggesting that erythrocytes can be used as prolonged release for pravastatin.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065791PMC
http://dx.doi.org/10.7150/ijms.8.222DOI Listing
March 2011

eComment: Myocardial protection in high risk coronary surgery.

Interact Cardiovasc Thorac Surg 2009 Nov;9(5):878

PSHC, King Fahd Medical City, Riyadh, Saudi Arabia.

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http://dx.doi.org/10.1510/icvts.2009.209437ADOI Listing
November 2009

Pediatric Non Metastatic Non Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTSS): Five Years Experience from NCI-Egypt.

J Egypt Natl Canc Inst 2008 Dec;20(4):395-402

The Departments of Pediatric Oncology, NCI, Cairo University.

Purpose: Evaluation of demographic, pathological, and clinical patterns in addition to treatment outcome of pediatric NRSTS patients treated at the NCI, Egypt.

Procedure: 21 pediatric patients of NRSTS between 2001 and 2006 were included. Clinical and pathological diagnosis and subtyping verification were done. Patients' cohort formed of 3 treatment groups. (1) Patients who underwent complete surgical resection with no adjuvant therapies. (2) Patients who received chemotherapy and complete surgical resection, and group (3) Patients with localized unrersectable tumors for whom systemic chemotherapy only was given. Demographic, clinicopathological variables, and treatment modalities were statistically evaluated and compared with the outcome.

Results: Tumors of unknown histiogenesis followed by MPNST and myxofibrosarcoma were the most frequent tumor subtypes. Low tumor grade was in favor of better outcome. With a median follow up of 2-years; respectively 100% and 81.1% of patients who had complete surgical resection of a localized disease with or without chemotherapy entered in CR (p=0.01). Local failure rate was 27.2% among CR patients (n=17). Two patients suffered local recurrance and one had distant disease metastasis.

Conclusions: Complete surgical resection with or without chemotherapy is the mainstay of therapy for localized NRSTS. Tumor grade and surgical resection of NRSTS are 2 important predictors of prognosis.

Key Words: Nonrhabdomyosarcoma - Soft tissue sarcoma - Pediatric.
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December 2008

Acute type A aortic dissection at seven weeks of gestation in a Marfan patient: case report.

J Card Surg 2008 Sep-Oct;23(5):569-70

Prince Salman Heart Center, King Fahad Medical City, Riyadh, KSA.

A 34-year-old Marfan patient at the seventh week of pregnancy presented with acute type A aortic dissection and severe aortic regurgitation. The aortic valve and ascending aorta were replaced successfully using circulatory arrest and deep hypothermia. At 35 weeks of gestation, the patient underwent a cesarean section and delivered a healthy baby. To our knowledge, this case is the first to report a favorable fetal outcome following surgical repair of acute dissection in the first trimester of pregnancy.
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http://dx.doi.org/10.1111/j.1540-8191.2007.00551.xDOI Listing
March 2009

eComment: acute type A aortic dissection at seven weeks of gestation in a Marfan patient.

Interact Cardiovasc Thorac Surg 2008 Oct;7(5):940

PSHC, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia.

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http://dx.doi.org/10.1510/icvts.2008.182766ADOI Listing
October 2008

Antithrombin after cardiac surgery: implications on short and mid-term outcome.

J Thromb Thrombolysis 2009 Jan 11;27(1):105-14. Epub 2008 Jan 11.

Dipartimento di Emergenza e Trapianti di Organo (D.E.T.O.), Division of Cardiac Surgery, University of Bari, Piazza Giulio Cesare 11, Bari, 70100, Italy.

Background: Antithrombin (AT) drop during cardiac surgery has been described. The causes and the effects of this phenomenon are not clear. The objective of the study is to evaluate the relationship of AT postoperative values on short and mid-term outcome after cardiac surgery.

Methods: Between January and June 2005, 405 patients, who underwent cardiac operations at our Institution had AT values available preoperatively and postoperatively. Using Receiver Operating Characteristic curves, a cut-off equal to 63.7% for ICU-arrival AT was chosen in order to divide the entire population in two groups (117 patients with ICU-arrival AT < 63.7%, Low AT group, and 288 patients with ICU-arrival AT > or = 63.7%, High AT group). Objective of the study was to evaluate the predictive role of ICU-arrival AT < 63.7% on in-hospital mortality and morbidity and on 18 months follow-up after cardiac surgery.

Results: ICU-arrival AT was significantly lower than preoperative AT (90.7 +/- 16.3% vs. 71.2 +/- 15.1%, P < 0.0001). Patients in the Low AT group were older, more often female, had a worse Euroscore and required longer CPB duration and cross clamp time. They had significantly higher preoperative and postoperative D-dimer levels. ICU arrival AT < 63.7% was not associated with increased in-hospital mortality but it was an independent risk factor for longer mechanical ventilation, need of inotropic support, excessive bleeding and blood products transfusion. ICU arrival-AT < 63.7% was associated with worse survival during 18 months follow up (92.3% vs. 85.4% in the High AT and Low AT group, respectively, P = 0.05).

Conclusions: Low AT after cardiac surgery is associated with higher incidences of peri-operative complications and worse survival in the mid-term. Future studies should clarify the pathophysiologic mechanism of this findings and possible therapeutic directions.
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http://dx.doi.org/10.1007/s11239-007-0191-9DOI Listing
January 2009

Coronary artery bypass grafting for Takayasu arteritis with severe coronary, carotid, subclavian, and renal artery involvement and subsequent pregnancy.

Interact Cardiovasc Thorac Surg 2006 Apr 20;5(2):153-5. Epub 2006 Jan 20.

Dallah Cardiac Center, Riyadh, Saudi Arabia.

Takayasu arteritis is a rare idiopathic large-vessel vasculitis that involves the aorta and its major branches. It affects young women in their child-bearing period. We present a case of a 32-year-old lady with a history of remittent fever. Magnetic resonance angiography and arch aortogram showed aortic involvement with critical stenosis of both carotid and subclavian arteries. She also had critical ostial left main and right coronary artery stenosis as well as severe renal arteries involvement. The patient underwent coronary artery bypass grafting. She did well and after 12 months she got pregnant. She had an uneventful pregnancy and delivery without flaring of symptoms.
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http://dx.doi.org/10.1510/icvts.2005.120832DOI Listing
April 2006

ICVTS on-line discussion B. VAC therapy in post cardiac surgery deep sternal wound infection.

Interact Cardiovasc Thorac Surg 2007 Aug;6(4):527-8

PSHC, King Fahd Medical City, Riyadh 11525, Saudi Arabia.

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http://dx.doi.org/10.1510/icvts.2007.157370BDOI Listing
August 2007

Seroprevalence of herpes simplex virus types 1 and 2, Epstein-Barr virus, and cytomegalovirus in children with acute lymphoblastic leukemia in Egypt.

Saudi Med J 2006 Aug;27(8):1139-45

Cancer Biology Department, Virology and Immunology Unit, National Cancer Institute, Fom El-Khalig, Cairo 11796, Egypt.

Objective: Viral infection, especially caused by herpes viruses, is now recognized as an important cause of morbidity and mortality in immunocompromised cancer patients. This study aimed at studying seroprevalence of 3 herpes viruses Herpes simplex virus types 1 and 2 (HSV 1 and 2), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in children with acute lymphoblastic leukemia (ALL).

Methods: We conducted this study on 68 newly diagnosed pediatric patients with ALL presented to the Pediatric Oncology Service of National Cancer Institute, Cairo University, Egypt from November 2001 to June 2003. We used enzyme-linked immunosorbent assay in detecting HSV 1 and 2, CMV, EBV antibodies of both types immunoglobulin (Ig) M and IgG detection of DNA for both CMV and EBV by polymerase chain reaction was carried out.

Results: High seroprevalence of HSV-1 and 2, CMV and EBV IgG antibodies in both leukemic children and their control was observed (69%, 100%, 83%) and (80%, 100%, 95%). Significantly higher percentage of HSV-1 and 2 IgM or reactivated infection was found among leukemic children 17/68 (25%) compared with normal control 0%. Analysis showed that prevalence of HSV 1 and 2 IgG increased from 18/33 (54%) in children <5 years to 11/13 (77%) in children >10 years, and reactivation of HSV-1 and 2 increased with increasing age from 1/33 (3%) in children <5 years to 4/13 (30%) in children >10 year. This was in contrast to seroprevalence of CMV and EBV IgG which were 100% and 83% in children <5 years. No difference in seroprevalence was found among both gender, and no difference was found in leukemic patients with granulocytopenia.

Conclusion: The data show a higher exposure to HSV-1 and 2 both primary infections and reactivation among ALL children. Therefore, acyclovir prophylaxis could be highly effective for seropositive leukemic patients who are undergoing induction chemotherapy.
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August 2006