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Genetic counseling and testing are more accessible than ever due to reduced costs, expanding indications and public awareness. Nonetheless, many patients missed the opportunity of genetic counseling and testing due to barriers that existed at that time of their cancer diagnoses. Given the identified implications of pathogenic mutations on patients' treatment and familial outcomes, an opportunity exists to utilize a 'traceback' approach to retrospectively examine their genetic makeup and provide consequent insights to their disease and treatment. In this study, we identified living patients diagnosed with breast cancer (BC) between July 2007 and January 2022 who would have been eligible for testing, but not tested. Overall, 422 patients met the eligibility criteria, 282 were reached and invited to participate, and germline testing was performed for 238, accounting for 84.4% of those invited. The median age (range) was 39.5 (24-64) years at BC diagnosis and 49 (31-75) years at the date of testing. Genetic testing revealed that 25 (10.5%) patients had pathogenic/likely pathogenic (P/LP) variants; mostly in BRCA2 and BRCA1. We concluded that long overdue genetic referral through a traceback approach is feasible and effective to diagnose P/LP variants in patients with history of BC who had missed the opportunity of genetic testing, with potential clinical implications for patients and their relatives., (© 2024. The Author(s).)

The surge in multidrug-resistant pathogens worldwide has jeopardized the clinical efficiency of many current antibiotics. This problem steered many researchers in their quest to discover new effective antimicrobial agents from natural origins including plants or their residing endophytes. In this work, we aimed to identify the endophytic fungi derived from Hedera helix L. and investigate their potential antimicrobial activity. Bioguided fractionation approach was conducted to isolate the pure compounds from the most active fungal fraction. Out of a total of six different isolated endophytic fungal strains, only Aspergillus cejpii showed the highest activity against all tested microbial strains. The most active fraction was the dichloromethane/methanol fraction (DCM:MeOH), where it showed significant activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Serratia marcescens, Acinetobacter baumannii, Salmonella typhi, and three drug-resistant clinical isolate strains including Methicillin-resistant Staphylococcus aureus (MRSA, H1), Pseudomonas aeruginosa (PS 16), and Acinetobacter baumannii (ACT 322) using tetracyline and kanamycin as the control antibiotics. Bioguided fractionation of the active fraction led to the isolation of the γ-butenolide, spiculisporic acid. Structure elucidation was carried out using 1 H and 13 C-NMR spectroscopic analysis. The compound showed good antimicrobial activities with minimum inhibitory concentration (MIC) values ranging from 3.9 to 31.25 μg/mL against all tested strains. Gas chromatography coupled to mass spectrometry (GC-MS) profiling was also carried out to identify the metabolites in the microbial crude extract. In conclusion, endophytic fungi, Aspergillus cejpii, isolated from Hedera helix L. roots showed promising antimicrobial activity which merits further in-depth investigations for potential utilization as a source of new antibiotics in the future. It can also be considered as a novel source for spiculisporic acid., (© 2024. The Author(s).)

Objective: This study aimed to address the prognostic impact of SOX2 and OCT3/4 expression on adult acute leukemia patients' outcomes., Methods: SOX2 and OCT3/4 expression by blast cells were evaluated by flow cytometry in 80 acute leukemia patients and 8 healthy controls., Results: Baseline SOX2 and OCT3/4 expression were significantly higher in both ALL (P = < 0.001, P = 0.005 respectively) and AML patients (P < 0.001, P = 0.003 respectively) as compared to control, and decline at complete remission (CR) and elevated again at relapse. High SOX2 and OCT3/4 levels were significantly correlated with the presence of adverse risk stratification parameters., Conclusion: Our findings indicated that both SOX2 and OCT3/4 could serve as biomarkers that could improve risk stratification of acute leukemia patients. Also, both SOX2 and OCT3/4 might be a therapeutic target, especially in resistant acute leukemia., (© 2024. The Author(s).)

Background: Inferior vena cava (IVC) filters serve as a vital intervention when systemic anticoagulation proves ineffective or contraindicated, particularly in the context of cancer patients. This study aimed to provide real-world insights into the outcomes of cancer patients following IVC filter placement., Patients and Methods: Cancer patients with IVC filters were retrospectively reviewed. The indications and survival outcomes following IVC filter insertion have been reported., Results: A total of 176 cancer patients with IVC filters were included in the study. The median patient age was 56 years (range: 18-88 years). Solid tumors were the most common primary cancers (n = 125, 71.0%), and the majority (n = 99, 79.2%) had the advanced-stage disease at the time of IVC insertion. The filters were inserted because of contraindications to anticoagulation (n = 99, 56.3%) or the failure of anticoagulation (n = 56, 31.8%). The median survival (range) following filter placement was only 2 (1.45-2.55) months for patients with advanced-stage solid tumors, 5 (0.62-9.38) months for patients with brain tumors, and 44 (8.59-79.41) months for those with early-stage solid tumors, p < 0.001., Conclusions: Our findings suggest that IVC filter placement offers limited benefits to patients with advanced-stage disease. The underlying tumor, stage, and life expectancy are crucial factors in the decision-making process before IVC filter insertion.

Background: Contrary to Western societies, more than 15% of patients with breast cancer in Jordan are diagnosed with stage IV disease. In this study, we evaluate the value of early palliative care integration in the end-of-life care of such patients., Methods: All consecutive adult patients who died between 2014 to 2018, while under the care of our institution, with a confirmed diagnosis of breast cancer at the time of death, irrespective of place of death, were retrospectively reviewed., Results: During the study period, a total of 433 patients, median age 51.6 years, were included in the analysis. Among the whole group, 102 (23.6%) were referred to palliative care service early (≥30 days prior to death), 182 (42.0%) had late referral (<30 days from death), while 149 (34.4%) were never referred and were followed up by their medical oncologists. During the last 30 days prior to death, patients who were never referred to palliative care were more likely to visit the Emergency Room (ER) more than once (OR 1.89, 95% CI 1.20-2.99, p = 0.006), more likely to be admitted to the hospital more than once (OR 2.27, 95% CI 1.38-3.73, p = 0.001), and more likely to be admitted to the intensive care unit (ICU) (OR 3.07, 95% CI 1.48-6.38, p = 0.0027). Fewer patients in the "no referral" group died with advance directives compared to those who had early or late referral; 60.8%, 75.0% and 82.5%, respectively, p = 0.0003. Survival of patients followed by medical oncologist was not better than those referred to palliative care, either late or early; median survival was 19.0, 19.1 and 23.8 months, respectively (p = 0.2338)., Conclusion: Findings suggest that earlier palliative care referral is associated with less aggressive end-of-life care, leading to less frequent ER visits, hospital and ICU admissions during the last month of life, and does not compromise survival., Competing Interests: The authors declared that they have no conflicting interest in this work., (© 2023 Abunasser et al.)

L-asparaginase is an antileukemic enzyme that hydrolyzes L-asparagine into L-aspartic acid and ammonia, causing cell starvation and apoptosis in susceptible leukemic cell populations. Currently, L-asparaginase obtained from bacterial sources is constrained by several issues, including lesser productivity, stability, selectivity, and higher toxicity. The goal of this study is to provide fungal L-asparaginase with in-vitro effectiveness towards different human carcinomas. L-asparaginase from endophytic Fusarium solani (Gene Bank accession number MW209717) isolated from the roots of the medicinal plant Hedera helix L. was characterized and optimized experimentally for maximum L-asparaginase production in addition to evaluating its subsequent cytotoxicity towards acute monocytic leukemia and human skin fibroblast cell lines. The enzyme production was maximized using potato dextrose media (15.44 IU/ml/hr) at the 5th and 6th days of fermentation with incubation temperature 30 °C, 3% asparagine, 150-180 rpm agitation rate and a 250 ml flask. Enzyme characterization studies revealed that the enzyme maintained its thermal stability with temperatures up to 60 °C. However, its optimal activity was achieved at 35 °C. On measuring the enzymatic activity at various temperatures and different pH, maximum enzyme activity was recorded at 40 °C and pH 8 using 0.1 M asparagine concentration. Results also revealed promising cytotoxic activity against acute monocytic leukemia with IC 50  = 3.66 µg/ml and low cytotoxicity against tested normal human skin fibroblast cell line which suggested that it might have selective toxicity, and consequently it could be used as a less toxic alternative to the current formulations., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Metastatic breast cancers (MBC) with no expression of human epidermal growth factor receptor-2 (HER2) are recently classified into two groups; HER2-zero [HER2-immunohistochemistry (IHC) score of 0 (IHC-0)] and HER2-low, defined as those with IHC score of 1+ or 2+ with negative in situ hybridization (ISH) assay. We investigate differences in treatment outcomes between both groups treated with endocrine therapy (ET) and the CDK4/6 inhibitor ribociclib., Methods: Data were retrospectively collected for patients with HR-positive+/HER2-negative MBC who received ribociclib with an aromatase inhibitor (AI) or fulvestrant and were divided into two groups: HER2-zero and HER2-low., Results: A total of 257 patients, median age 48 (22-87) years, all with MBC who were treated with ET and ribociclib were enrolled. One hundred and thirty-seven (53.3%) patients had de novo MBC, and majority (n = 162, 63.0%) received ribociclib as a first-line therapy. In total, 114 (44.4%) patients had HER2-zero (IHC-0), while 143 (55.6%) others had HER2-low disease. The overall response rate (ORR) was 52.0% for the HER2-zero group compared to 39.4% for the HER2-low group, p = 0.005. The median PFS was 22.2 (95% confidence interval [CI], 19.4-NR) months for HER2-zero versus 17.3 (95% CI, 14.1-20.6) months for HER2-low, P = 0.0039. In multivariable analysis, HER2-low expression remained significant determinant of inferior PFS after adjusting for other factors, including the site of metastasis, prior chemotherapy, and the line of treatment., Conclusion: In patients with MBC treated with ET and ribociclib, level of HER2 negativity may affect treatment outcomes; patients with HER2-zero had better response rate and PFS compared to those with HER2-low disease. These findings, if confirmed in larger studies, may help oncologists select patients with HER2-low for better treatment options., Competing Interests: The authors declared that they have no conflicting interest., (© 2023 Sharaf et al.)

Background: Genetic testing for at-risk patients with breast cancer should be routinely offered. Knowledge generated may influence both treatment decisions and cancer prevention strategies among the patients themselves and their relatives. In this study, we report on the prevalence and patterns of germline mutations, using commercially available next-generation sequencing (NGS)-based multi-gene panels (MGP)., Patients and Methods: Consecutive at-risk breast cancer patients, as determined by international guidelines, were offered germline genetic testing using a 20-gene NGS-based panel at a reference lab. Samples of peripheral blood were obtained for DNA extraction and genetic variants were classified as benign/likely benign (negative), pathogenic/likely pathogenic (positive) or variants of uncertain significance (VUS)., Results: A total of 1310 patients, median age (range) 43 (19-82) years, were enrolled. Age ≤45 years (n = 800, 61.1%) was the most common indication for testing. Positive family history of breast, ovarian, pancreatic or prostate cancers, and triple-negative disease were among the common indications. Among the whole group, 184 (14.0%) patients had pathogenic/likely pathogenic variants; only 90 (48.9%) were in BRCA1 or BRCA2 , while 94 (51.9%) others had pathogenic variants in other genes; mostly in APC, TP53, CHEK2 and PALB2 . Mutation rates were significantly higher among patients with positive family history (p = 0.009); especially if they were 50 years or younger at the time of breast cancer diagnosis (p < 0.001). Patients with triple-negative disease had relatively higher rate (17.5%), and mostly in BRCA1/2 genes (71.4%). Variants of uncertain significance (VUS) were reported in 559 (42.7%) patients; majority (90.7%) were in genes other than BRCA1 or BRCA2 ., Conclusion: Pathogenic mutations in genes other than BRCA1/2 are relatively common and could have been missed if genetic testing was restricted to BRCA1/2 . The significantly high rate of VUS associated with multi-gene panel testing can be disturbing., Competing Interests: First author HA received an institutional grant from Pfizer International to study genetic mapping of breast cancer. All other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, this includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The abstract of this paper was presented at the 44th annual Breast Cancer Symposium (7–10 Dec 2021) as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts”, Cancer Res 2022; 82(4 Suppl): Abstract number P3-07-06. Link, https://doi.org/10.1158/1538-7445.SABCS21-P3-07-06, (© 2023 Abdel-Razeq et al.)

Background: Refining risk stratification of cytogenetically  normal AML (CN-AML) cases is important for decision making and tailoring of therapy. In this context genetic and epigenetic mutations was considered. Among these epigenetic regulators are DNMT3A & TET2 genes. Therefore, the aim of  this study was to determine the prevalence of DNMT3A and TET2 genes mutations and their impact on the outcome of  adult AML patients., Subjects and Methods: The present study is cross sectional study which was conducted on 39 adult CN-AML patients at diagnosis. For all included patients sanger sequencing was done for DNMT3A exon 23 and TET2 exon 3 genes., Results: DNMT3A mutations were detected in 8 of 39 patients (20.5%), and in 5 of 39 patients(12.8%) in TET gene. Two CN-AML  patients had combined mutations in both genes. All of the mutations detected were missense and only one was frame shift. Mutated TET2 or DNMT3A genes were significantly associated with failure of complete remission (CR) (p <0.001), higher mortality rate, shorter OS (mean=16 versus 22.7 months) and shorter DFS (mean= 9.5 versus 21.4 months) when compared to non-mutated ones., Conclusion: Mutated TET2 and DNMT3A detection define a subgroup of CN-AML patients with poor outcome.

Purpose: Cyclin dependent kinase (CDK) 4/6 inhibitors (palbociclib, ribociclib and abemaciclib) modulate endocrine resistance and are integral treatment for patients with advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Since their approval, CDK4/6 inhibitors are widely used in clinical practice. Thromboembolic events (TEE) were not a major issue in patients treated on clinical trials utilizing these agents. However, conflicting data started to emerge describing higher than expected rates of both arterial and venous thrombosis in patients treated with CDK4/6 inhibitors. In this study, we report our experience on TEE in patients treated with one of these agents (ribociclib) in real-world settings., Patients and Methods: All consecutive patients with metastatic breast cancer (mBC) treated with ribociclib combined with letrozole or fulvestrant were retrospectively reviewed. All episodes of radiologically confirmed arterial or venous thrombosis were recorded. TEE was considered ribociclib-related if diagnosed while patients are on the drug, or within 4 weeks after the last dose., Results: A total of 305 patients, median age (range), 49 (22-87) years were enrolled. All patients had metastatic disease, and most (n=241, 79.0%) were with visceral metastasis. Ribociclib was used for a median duration of 7 months (range: 1-45) and was used beyond the first-line setting in 110 (35.9%) patients. TEE were confirmed on 6 (1.97%) patients; 3 were pulmonary embolism, 2 cerebral venous sinus thrombosis (CVST), and one case of limb ischemia and all were symptomatic. Similar rates of TEE were noted prior to initiation, and after stopping ribociclib., Conclusion: In real-world settings, breast cancer patients treated with ribociclib, combined with aromatase inhibitors or fulvestrant, may not be at higher risk for thromboembolic events. However, unusual sites of thrombosis, like CVST, may raise some concerns., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Abdel-Razeq et al.)

Ammi majus L., an indigenous plant in Egypt, is widely used in traditional medicine due to its various pharmacological properties. We aimed to evaluate the anticancer properties of Ammi majus fruit methanol extract (AME) against liver cancer and to elucidate the active compound(s) and their mechanisms of action. Three fractions from AME (Hexane, CH 2 Cl 2 , and EtOAc) were tested for their anticancer activities against HepG2 cell line in vitro (cytotoxicity assay, cell cycle analysis, annexin V-FITC apoptosis assay, and autophagy efflux assay) and in silico (molecular docking). Among the AME fractions, CH 2 Cl 2 fraction revealed the most potent cytotoxic activity. The structures of compounds isolated from the CH 2 Cl 2 fraction were elucidated using 1 H- and 13 C-NMR and found that Compound 1 (xanthotoxin) has the strongest cytotoxic activity against HepG2 cells (IC 50 6.9 ± 1.07 µg/mL). Treating HepG2 cells with 6.9 µg/mL of xanthotoxin induced significant changes in the DNA-cell cycle (increases in apoptotic pre-G1 and G2/M phases and a decrease in the S-phase). Xanthotoxin induced significant increase in Annexin-V-positive HepG2 cells both at the early and late stages of apoptosis, as well as a significant decrease in autophagic flux in cancer compared with control cells. In silico analysis of xanthotoxin against the DNA-relaxing enzyme topoisomease II (PDB code: 3QX3) revealed strong interaction with the key amino acid Asp479 in a similar fashion to that of the co-crystallized inhibitor (etoposide), implying that xanthotoxin has a potential of a broad-spectrum anticancer activity. Our results indicate that xanthotoxin exhibits anticancer effects with good biocompatibility toward normal human cells. Further studies are needed to optimize its antitumor efficacy, toxicity, solubility, and pharmacokinetics.

Background The central nervous system international prognostic index (CNS-IPI) is being used widely for the identification of patients with diffuse large B cell lymphoma (DLBCL) with a high risk of central nervous system (CNS) relapse. The aim of our study is to confirm the value of the CNS-IPI in predicting CNS relapse in our young study population and to evaluate its impact on the selection of patients for CNS prophylaxis. Methods We retrospectively reviewed patients diagnosed with DLBCL who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) regimen from January 2010 till December 2018. Correlation between CNS-IPI and cumulative incidence of CNS relapse and time to CNS relapse was examined through Kaplan-Meier plots. Median time to CNS relapse and median overall survival after CNS relapse were also estimated using the Kaplan-Meier plots.  Results A total of 354 patients were included. The median age was 46 years. Overall, 5% of the patients developed CNS relapse. Median survival after CNS relapse was seven months. Two-year CNS relapse rates according to CNS-IPI were 0.7%, 5.1%, and 26% for low, intermediate, and high-risk, groups respectively. On multivariate analysis, poor performance status (p=0.045), involvement of two or more extranodal sites (p= 0.021), involvement of bone marrow (p= 0.029), and renal or adrenal glands (p= 0.006) significantly correlated with CNS relapse. Considering the CNS-IPI and high-risk anatomical sites (breast, uterus, testis, and epidural space), 26% of our patients with DLBCL would have needed prophylaxis. Conclusion Although CNS-IPI helps in better selection of DLBCL patients for CNS prophylaxis, it can possibly increase the number of patients exposed to unnecessary prophylaxis. More investigational biomarkers are needed to better refining high-risk patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Ma'koseh et al.)

Background: Among all subtypes, patients with triple-negative (TN) breast cancer is known for their poor outcome and their higher risk of harboring BRCA1 or BRCA2 pathogenic mutations. Identification of such mutations has clinical impact on breast and ovarian cancer prevention and treatment decisions. We here report on patterns and prevalence of BRCA1 and BRCA2 mutations among Arab patients diagnosed with TN subtype., Patients and Methods: Patients with TN-breast cancer (n=197) were enrolled regardless of their age or family history. Following a detailed genetic counseling, BRCA1/2 testing was performed at reference labs. BRCA1 and BRCA2 variants were classified as negative, pathogenic/likely pathogenic (positive) and variants of uncertain significance (VUS)., Results: Median age of enrolled patients was 42 (range, 19-74) years and 27 (13.7%) were non-Jordanian Arabs. Among the study group, 50 (25.4%) were tested positive for BRCA1 (n=36, 18.3%) or BRCA2 (n=14, 7.1%), while 14 (7.1%) others had VUS. Compared to older ones, mutation rates were higher among patients <40 years (32.9%, P= 0.034), those with close relatives with breast, ovarian, pancreatic or prostate cancer (37.8%, P=0.002) and those with two or more breast cancers (41.4%, P=0.032). Among eligible patients, 23 (63.9%) patients underwent prophylactic mastectomy, while 19 (52.8%) patients had risk-reducing salpingo-oophorectomy. None of the patients with VUS underwent any prophylactic surgery., Conclusion: Arab patients with TN-breast cancer have relatively high BRCA1 or BRCA2 mutation rates. Young age at diagnosis and personal and family history of breast cancer further increase this risk., Competing Interests: The authors reported no conflicts of interest for this work., (© 2021 Abdel-Razeq et al.)

Background: Khella ( Ammi visnaga Lam.) fruits (Apiaceae) are rich in furanochromones, mainly khellin and visnagin, and are thus incorporated in several pharmaceutical products used mainly for treatment of renal stones., Methods: The objective of this study was to compare the yield of khellin and visnagin obtained using different conventional solvents and supercritical fluid extraction (SCFE) with carbon dioxide (containing 5% methanol as co-solvent). Water, acetone and ethanol (30% and 95%) were selected as conventional solvents., Results: Highest extract yield was obtained from 30% ethanol (15.44%), while SCFE gave the lowest yield (4.50%). However, the percentage of furanochromones were highest in SCFE (30.1%), and lowest in boiling water extract (5.95%). HPLC analysis of conventional solvent extracts showed other coumarins that did not appear in supercritical fluid extraction chromatogram due to non-selectivity of solvent extraction. Ammi visnaga extracts as well as standard khellin and visnagin were tested for their cytotoxic activity using sulforhodamine B assay on breast cancer (MCF-7) and hepatocellular carcinoma (Hep G2) cell lines. Results revealed a strong cytotoxic activity (IC 50 < 20 µg/mL) for the SCFE and standard compounds (khellin and visnagin) (IC 50 ranging between 12.54 ± 0.57 and 17.53 ± 1.03 µg/mL). However, ethanol and acetone extracts had moderate cytotoxic activity (IC 50 20-90 µg/mL) and aqueous extract had a weak activity (IC 50 > 90 µg/mL)., Conclusions: Thus, supercritical fluid extraction is an efficient, relatively safe, and cheap technique that yielded a more selective purified extract with better cytotoxic activity.

Purpose: Breast cancer that overexpresses the human epidermal growth factor receptor-2 (HER2) and both estrogen (ER) and progesterone (PR) receptors is recently recognized as a subtype (triple-positive) with distinctive behavior and response to treatment. In this study, we investigate the treatment outcomes and the beneficial effect of anti-HER2 treatment in relation to level of hormone-receptor (HR) expression., Methods: Consecutive breast cancer patients with triple-positive disease, diagnosed, treated and followed at our institution between 2006 and 2016 were enrolled. Disease-free survival (DFS) was studied in relation to the level of HR-positivity., Results: During the study period, a total of 312 were enrolled; median age (range) was 47 (20-83) years. Fifty (16.0%) of the enrolled patients received adjuvant chemotherapy without trastuzumab (cohort A). All remaining patients were treated with both chemotherapy and trastuzumab and were divided into two groups: Cohort B with both ER and PR scores ≥ 50% (n = 130, 41.7%) and Cohort C with ER and/or PR < 50% (n = 132, 42.3%). After a median follow-up of 47 months, 14 (28.0%), 30 (23.1%) and 20 (15.2%) patients in cohorts A, B, and C had an event in a form of local/system relapse or death while disease-free. The estimated 5-year DFS was 56.2%, 75.4%, and 80.8%, respectively, and at 7 year was 56.2%, 67.1%, and 78.0%, respectively (p < 0.001)., Conclusions: HER2-positive tumors are not homogeneous; stronger ER/PR co-expression may weaken the beneficial effect of anti-HER2 therapy. Such findings may have potential implication on modifying anti-HER2 treatment based on the strength of HR expression.

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher ( P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

Background: The data about the clinical impact of NOTCH1 mutations among Egyptians B - cell chronic lymphocytic patients is not previously identified. We herein, evaluate the prevalence and the prognostic significance of neurogenic locus notch homolog protein-1 (NOTCH1) mutations in B- cell lymphocytic leukemia (B-CLL)., Methods: A cohort of 105 Egyptian B-CLL patients aging from 43 to 86 years. PCR products including NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline (P), glutamic acid (E), serine (S), threonine (T) (PEST domains) were sequenced by direct DNA Sanger sequencing., Results: NOTCH1 mutations were detected in 48/105 of patients (45.7%). Mutations in B-CLL patients are insertions (n=21), point mutations (n=18) and deletions (n=12). NOTCH1 mutations showed significant impact on prognosis of B-CLL patients as they were associated with increased bone marrow lymphocytes, more relapse and  high incidence of mortality, shortened overall survival and progression free survival, and lymphocytes doubling time, when compared with NOTCH1 wild type B-CLL patients (P= 0.001; 0,005; 0.042; 0.049; 0.008; 0.049 respectively)., Conclusion: NOTCH1 mutations were considered as bad prognostic marker in B-CLL and suggested to be included in risk stratification of B-CLL patients at diagnosis.

Myrrh is the resinous exudate obtained by the incision in Commiphora molmol trees (Family Burseraceae). The bactericidal activity of its hexane extract was compared to its essential oil (MEO) using viable count technique against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (Ps. aeruginosa). MEO exhibited a better activity with > 99.999% killing of both tested strains after 2 h contact time. MEO was tested using the same technique against four multidrug resistant isolates: S. aureus (MRSA, sputum), Escherichia coli (E. coli, urine), Ps. aeruginosa (wound) and Klebsiella pneumonia (K. pneumonia, sputum). Highest bactericidal activity was observed against Ps. aeruginosa while lowest was against K. pneumonia (99.59 and 54.04% killing, respectively after 2 h contact time). A cream and mouthwash were formulated using 5% v/v MEO. The cream showed a better activity against Ps. aeruginosa than S. aureus (95.11 and 86.76% killing, respectively after 2 h contact time). The in vitro treatment of ca 10 7  CFU/ml S. aureus cells suspended in 10% saliva with the mouthwash produced ca 46% killing within the first 15 min reaching ca 99.999% after 30 min. Cytotoxic studies of both the essential oil and hexane extract on human liver cancer (Hep G2), human breast cancer (MCF-7) and colon cancer cell lines (HCT-116) revealed a promising in vitro activity. Highest activity was recorded for the essential oil on MCF-7 with IC 50 10.93 ± 0.32 μg/ml. GC/MS analysis allowed the identification of 17 and 9 compounds representing 92.01 and 99.99% of the hexane extract and essential oil, respectively. Furano-eudesma-1,3-diene (15.99%) and 2-acetoxy-furano-diene (26.82%) were the major identified compounds in the hexane extract and essential oil, respectively. These results indicate that Myrrh essential oil is a promising antibacterial and cytotoxic agent that can be formulated in suitable dosage forms.

Ammi visnaga L. ( Visnaga daucoides Gaertn., Family Apiaceae), also known as Khella Baldi or toothpick weed, is an annual or biennial herb indigenous to the Mediterranean region of North Africa, Asia, and Europe. The plant is known to have been used in traditional medicine a long time ago. Nowadays, it is used in modern medicine to treat many aliments such as renal colic and coronary insufficiency, and is used as an antioxidant, antifungal, and antibacterial, with a larvicidal effect on mosquito larvae. Peer-reviewed studies show that these pharmacological activities are due its valuable chemical constituents that include mainly essential oil, polyphenolic compounds including flavonoids, as well as γ-pyrones, represented mainly by khellin and visnagin. Its essential oil is reported to have antiviral, antibacterial, and larvicidal effects, while its flavonoid content is responsible for its antioxidant activity. Its γ-pyrone content has a powerful effect on facilitating the passage of kidney stones and relieving renal colic, in addition to having a relaxant effect on smooth muscle including that of the coronary arteries. The current review represents the progress in research on A . visnaga in terms of either its chemistry or biological activities. This review represents scientific support material for the use of the plant by the pharmaceutical industry.

Background: This study aimed to determine the prevalence and clinical impact of neurogenic locus notch homolog protein 1 (NOTCH1) mutations among patients with T cell acute lymphoblastic leukemia (T-ALL)., Patient and Methods: A cohort of 60 T-ALL cases was included in this study. Sanger sequencing were done for NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline, glutamic acid, serine, threonine (PEST) domains in all studied T ALL patients at diagnosis., Results: NOTCH1 mutations was detected in 40 out of 60 T-ALL patients (66%). Mutations in T-ALL patients are deletions (22 mutations) and point mutation (10 mutations). NOTCH1 mutations was found to have no significant impact on clinical outcome and prognosis in T-ALL including overall survival, progression free survival, relapse and mortality (P> 0.05 for all)., Conclusion: NOTCH1 mutations were frequently detected in T All patients; however, these mutations did not affect the T ALL patient's outcome. The high prevalence of NOTCH1 mutations at diagnosis could be used for detection of minimal residual disease in T ALL.

Ammi majus L.; Family Apiaceae; is a plant indigenous to Egypt. Its fruits contain bioactive compounds such as furanocoumarins and flavonoids of important biological activities. An endophytic fungus was isolated from the fruits and identified as Aspergillus amstelodami (MK215708) by morphology, microscopical characterization, and molecular identification. To our knowledge this is the first time an endophytic fungus has been isolated from the fruits. The antimicrobial activity of the Ammi majus ethanol fruits extract (AME) and fungal ethyl acetate extract (FEA) were investigated, where the FEA showed higher antimicrobial activity, against all the tested standard strains. Phytochemical investigation of the FEA extract yielded five prenylated benzaldehyde derivative compounds isolated for the first time from this species: Dihydroauroglaucin (1), tetrahydroauroglaucin (2), 2-(3,6-dihydroxyhepta-1,4-dien-1-yl)-3,6-dihydroxy-5-(dimethylallyl)benzaldehyde (3), isotetrahydroauroglaucin )4), and flavoglaucin (5). Structure elucidation was carried out using (1H- and 13C-NMR). Fractions and the major isolated compound 1 were evaluated for their antimicrobial and antibiofilm activity. Compound 1 showed high antimicrobial activity against Escherichia coli with minimum inhibitory concentration (MIC) = 1.95 µg/mL, Streptococcus mutans (MIC = 1.95 µg/mL), and Staphylococcus aureus (MIC = 3.9 µg/mL). It exhibited high antibiofilm activity with minimum biofilm inhibitory concentration (MBIC) = 7.81 µg/mL against Staphylococcus aureus and Escherichia coli biofilms and MBIC = 15.63 µg/mL against Streptococcus mutans and Candida albicans and moderate activity (MBIC = 31.25 µg/mL) against Pseudomonas aeruginosa biofilm. This reveals that dihydroauroglaucin, a prenylated benzaldehyde derivative, has a broad spectrum antimicrobial activity. In conclusion, it was observed that the MICs of the FEA are much lower than that of the AME against all susceptible strains, confirming that the antimicrobial activity of Ammi majus may be due to the ability of its endophytic fungi to produce effective secondary metabolites.

The aim of this work is to characterize the active constituents present in the ethyl acetate fraction of Senna tora , L. Roxb. seeds. Due to the fact that the main biological activity of S. tora, L seeds is attributed to its phenolic compounds which are mainly isolated from Ethyl acetate fraction, to avoid repetition of work and to save time, it was deemed necessary to confirm the identity of these phenolic compounds. This was done by GC-MS and LC-MS analysis of the ethyl acetate fraction where the structures of the isolated compounds were established on the basis of molecular ion peak and their fragmentation pattern. They were identified as Chrysophanol, Chrysarobin, 10-hydroxy-5-methoxy-2-methyl-1, 4-anthracenedione, Rubrofusarin, Parietin, Griseoxanthone-B, Isotorachrysone, and Cumbiasin B.

LC-ESI-MS/MS was used for a comprehensive characterisation of ethanol extract from the leaves of three Pistacia species. After optimisation of the method and the use of the negative ionisation mode, a total of 42 different compounds were identified, of which 22 were tentatively characterised in P. chinensis Bunge , 33 in P. khinjuk stocks and 25 in P. lentiscus L. leaves. Flavonoids, phenolic acids, and their derivatives were the most abundant identified compounds . LC-ESI-MS/MS revealed identification of 15, 18 and 6 not previously detected compounds in P. chinensis Bunge, P. khinjuk Stocks and P. lentiscus L., respectively. The three extracts were also tested for their cytotoxic activities against human PC3 prostate cancer, A549 lung cancer, MCF7 breast cancer and HepG2 liver cancer. Generally, all the extracts have a moderate cytotoxic activity against lung, breast and prostate cancer, with different IC 50 . However, only P. lentiscus L. showed moderate activity against liver cancer.

Origanum vulgare L. (Lamiaceae) is a widespread flavoring culinary and medicinal herb. The present study aimed at investigating the antimicrobial activity of Origanum vulgare (OV) essential oil (EO) through illustrating its biostatic, biocidal and the dynamics of the biocidal activity against 11 different microorganisms. GC/MS of OV EO allowed the identification of 32 compounds representing 99.94% of the oil. The two major identified compounds were terpinen-4-ol (38.35%) and trans-sabinene hydrate (10.06%). Different methods were employed to illustrate the biostatic activity of OV EO. Results of the biostatic studies on OV EO using agar and broth dilution methods showed that Staphylococcus aureus (S. aureus) was the most sensitive organism; with a Minimum inhibitor concentration (MIC) 1.18 mg/ml. Agar diffusion method showed that the highest activity was observed against Bordetella bronchiseptica (Br. bronchiseptica), Saccharomyces cerevisiae (S. cerevisiae), Bacillus subtilis (B. subtilus) and Staphylococcus epidermidis (S. epidermidis) with inhibition zones 38 ± 1.5, 29.5 ± 0.8, 26.9 ± 0.9 and 26.9 ± 1.1 mm, respectively. Studying the dynamics of 1% v/v OV essential oil emulsion over a period of 6 h revealed that Escherichia coli (E. coli), B. subtilis, S. epidermidis and S. cerevisiae had the fastest response. Also increasing concentrations of OV oil emulsion increased the rate of cell killing and the duration of growth lag phase increased correspondingly. These data indicated that OV EO produces a concentration and time-dependent antimicrobial activity.

Polyphenolic compounds are considered valuable secondary plant metabolites owing to the myriad of biological activities they exert. This study aimed to investigate the effect of applying various concentrations of the plant growth regulator, salicylic acid (SA), on Thymus vulgaris L. while subjecting the plant to decreasing amounts of irrigation water. The following parameters were monitored; total polyphenolic and flavonoid content, yield and composition of the essential oil, and antioxidant activity of the alcoholic extracts. Drought alone significantly (P < 0.05) increased the polyphenolic and flavonoid content, yield of the essential oil and antioxidant activity. The total flavonoid content in control plants was 6.1 ± 0.3 mg/gm dry weight calculated in terms of rutin equivalent. However, in drought stressed plants, (irrigated at 25% of the field capacity) sprayed with 3 mM SA, the flavonoid content increased to 32.1 ± 0.1 mg/gm dry weight calculated in terms of rutin equivalent. Moreover, the total phenolic content increased from 8.5 ± 0.3 to 68.5 ± 1.2 mg/gm dry weight calculated in terms of gallic acid in the same test plants. Radical scavenging activity, using DPPH assay, was measured for the different plant treatments. A decrease from 74.4 ± 0.4 μg/ml to 36.6 ± 0.9 μg/ml of IC 50 was recorded in the drought stressed plants (25% FC) sprayed with 3 mM SA compared with the control plants. The variability in polyphenolic composition between the control plants and plants with the highest total polyphenolic content was investigated by UPLC-ESI-MS/MS. Rosmarinic acid was detected as the major component in samples from both treatments, with a higher percentage observed upon subjecting the plant to the test conditions (25% FC and sprayed with 3 mM SA). The highest yield of the essential oil (1 ± 0.06 %v/w) was obtained from drought stressed plants (25% FC) sprayed with 2 mM SA. GC/MS analysis of oil samples revealed that the Thymol content increased with drought stress, while that of p-cymene decreased. However, an increase of p-cymene was witnessed as a result of SA spraying., (Copyright © 2017. Published by Elsevier Masson SAS.)

The camel industry uses traditional (i.e., iron brands and ear tags) and modern (i.e., microchips) identification (ID) systems without having performance results of reference. Previously iron-branded ( = 45; 1 yr) and microchipped ( = 59; 7 yr) camels showed problems of healing (8.6% of brands) and reading (only 42.9% of brands and 69.5% of microchips were readable), which made their use inadvisable. With the aim of proposing suitable ID systems for different farming conditions, an on-field study was performed using a total of 528 dromedaries at 4 different locations (Egypt, = 83; Spain, = 304; Saudi Arabia, = 90; and Tunisia, = 51). The ID devices tested were visual (button ear tags, 28.5 mm diameter, = 178; double flag ear tags, 50 by 15 mm, = 83; both made of polyurethane) and electronic (ear tags, = 90, and rumen boluses, = 555). Electronic ear tags were polyurethane-loop type (75 by 9 mm) with a container in which a 22-mm transponder of full-duplex technology was lodged. Electronic boluses of 7 types, varying in dimensions (50 to 76 mm length, 11 to 21 mm width, and 12.7 to 82.1 g weight) and specific gravity (SG; 1.49 to 3.86) and each of them containing a 31-mm transponder of half-duplex technology, were all administered to the dromedaries at the beginning of the study. When a low-SG bolus was lost, a high-SG bolus was readministered. Readability rates of each ID system were evaluated during 1 to 3 yr, according to device and location, and yearly values were estimated for comparison. On a yearly basis, visual ear tag readability was not fully satisfactory; it was lower for rectangular ear tags (66.3%) than for button ear tags (80.9%). Yearly readability of electronic ear tags was 93.7%. Bolus readability dramatically varied according to their SG; the SG < 2.0 boluses were fully lost after 8 mo. In contrast, the SG > 3.0 boluses were efficiently retained (99.6 to 100%) at all locations. In conclusion, according to the expected long lifespan of camels, low ID performances were observed for iron brands, injectable microchips, and ear tags (visual and electronic), making their use inadvisable as unique ID systems in camels. The high readability of dense electronic boluses recommended their use as a permanent ID device of reference in camels.

Background: Serum thrombopoietin in thrombocytopenic infants is largely related to the cause of thrombocytopenia and the underlying disease. Many perinatal factors can affect thrombopoietin level., Patients and Methods: A prospective cross-sectional study on 119 thrombocytopenic neonates: 54 full term and 65 preterm had been conducted. Thrombopoietin assay was done using a qualitative enzyme-linked immunosorbent assay technique. The test was repeated on the change of clinical status (recovery or deterioration)., Results: Lowering of thrombopoietin level was noted on reversal of platelet count to normal (P<0.001). Survival is significantly related to platelet count in full term (P = 0.04), but insignificant among thrombocytopenic preterms. Platelet count is negatively correlated to thrombopoietin level in neonates both in full term and preterm (r = -0.59, -0.69, respectively, P<0.001). Platelet count was found to be the best predictor for duration of recovery of thrombocytopenia in neonates compared with other factors including thrombopoietin level., Conclusion: Thrombocytopenic neonates had high levels of thrombopoietin. Despite the high thrombopoietin level in neonates died with severe thrombocytopenia, yet, mortality is related to the cause and outcome of thrombocytopenia rather than the serum thrombopoietin level. It is recommended to diagnose and treat the underlying cause of thrombocytopenia rather than to generalize the therapy based on thrombopoietin level.

Myrrh has long been used for its circulatory, disinfectant, analgesic, antirheumatic, antidiabetic, and schistosomicidal properties. Myrrh essential oil (MEO) was extracted from the oleo-gum resin of Commiphora molmol and formulated into emulsions and suppositories to mask/avoid its bitter taste. Three oil-in-water emulsions (E1-E3) were formulated and taste was evaluated by 10 volunteers. Particle size distribution was measured and correlated with excipients and the method of preparation. Physical and chemical stability testing was carried out for the optimum formulation (E2). Seven suppository formulations were investigated (F1-F7). Suppocire AML (F1) and Suppocire CM (F2) were chosen as fatty bases, and polyethylene glycol (PEG) 1500 (F3), PEG 4000 (F4), and a PEG blend (50% PEG 6000 + 30% PEG 1500 + 20% PEG 400) (F5) were chosen as water-soluble bases. A blend of PEG 1500 and Suppocire CM was also used (F7). Camphor (5%) was added to PEG 1500 (F6). Disintegration time, release rate, DSC, fracture points, and weight uniformity were evaluated. The overall average bitterness for formulations E1, E2, and E3 was 6.44, 4.15, and 3.45, respectively. Suppositories containing Suppocire AML had the fastest disintegration time (1.5 min) with dissolution efficiency (DE) of 56.8%. F3 containing PEG 1500 had a fast disintegration time of 2.5 min and maximum DE of 93.5%. The PEG blend had satisfactory release: (DE = 90.9%). A mixed fatty and water-soluble base (F7) had a disintegration time of 5 min and low DE (33.4%). A stable MEO emulsion with acceptable taste was formulated to improve patient acceptance and compliance. F3 suppositories yielded satisfactory results, while formulations containing fatsoluble bases exhibited poor release.

There is a traditional belief in the Middle East that regular consumption of camel milk may aid in prevention and control of diabetes. The aim of this work was to evaluate the efficacy of camel milk as an adjuvant therapy in young type 1 diabetics. This 16-week randomized study enrolled 54 type 1 diabetic patients (average age 20 years) selected from those attending the outpatient diabetes clinic of the Menofia University Hospital, affiliated with Egypt's National Cancer Institute. Subjects were randomly divided into two groups of 27 patients: one received usual management (diet, exercise, and insulin), whereas the other received 500 mL of camel milk daily in addition to standard management. A control group of 10 healthy subjects was also assessed. The following parameters were evaluated at baseline and at 4 and 16 weeks: hemoglobin A1c (HbA1c), human C-peptide, lipid profile, serum insulin, anti-insulin antibodies, creatinine clearance, albumin in 24-hour urine, body mass index, and Diabetes Quality of Life score. The following parameters were significantly different between the usual-management group versus the camel milk group after 16 weeks: fasting blood sugar (227.2 +/- 17.7 vs. 98.9 +/- 16.2 mg/dL), HbA1c (9.59 +/- 2.05[%] vs. 7.16 +/- 1.84[%]), serum anti-insulin antibodies (26.20 +/- 7.69 vs. 20.92 +/- 5.45 microU/mL), urinary albumin excretion (25.17 +/- 5.43 vs. 14.54 +/- 5.62 mg/dL/24 hours), daily insulin dose (48.1 +/- 6.95 vs. 23 +/- 4.05 units), and body mass index (18.43 +/- 3.59 vs. 24.3 +/- 2.95 kg/m(2)). Most notably, C-peptide levels were markedly higher in the camel milk group (0.28 +/- 0.6 vs. 2.30 +/- 0.51 pmol/mL). These results suggest that, as an adjunct to standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at least in part by boosting endogenous insulin secretion.

The leaf extract and its fractions of Peganum harmala L. have shown pronounced mortal effect, decreased percent pupation and adult emergence of the cotton leaf worm, Spodoptera littoralis Boisd. The third instar larvae fed for two days on treated leaves were more susceptible to plant extract and its ethyl acetate and chloroform fractions. The active lowest concentration (5%) of the leaf fractions of P. harmala showed significant effect on the percentage of emerged adult parasitoids, Microplitis rufiventris Kok. GC/MS analysis showed the major constituent in ethyl acetate fraction was (23S) ethylcholest-5-en-3 beta-ol (28.04%) while those of chloroform fraction were hydroxyfuranocoumarin (Bergaptol) (15.68%), piperidinone (12.08%), thymol (11.82%), phosphoric acid, tributyl ester (9.80%) and trimethyl-nonenol (9.66%). The medicinal plant P. harmala could be carefully applied in integrated pest management due to its strong effect on cotton leaf worm pest.

Angiogenesis is an important event in the survival and progression of solid tumors. The angiogenic status and the exact role of the angiogenic cytokines in lymphoid leukemia has not been fully elucidated. We have investigated the profile of the systemic components of angiogenic regulation in B-lineage acute lymphoblastic leukemia (B-ALL) and B-chronic lymphocytic leukemia (B-CLL), namely vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), endostatin and matrix metalloproteinase-9 (MMP-9) using enzyme-linked immunosorbent assay (ELISA). In B-ALL patients, sVEGF, and MMP-9 were significantly lower than control levels at diagnosis (p < 0.001) and increased to near control levels in remission (p>0.05). Both serum TNF-alpha and endostatin levels showed no significant difference at diagnosis (p>0.05) and in remission (p>0.05) compared to control levels. VEGF, TNF-alpha, MMP-9 and endostatin levels were not significantly correlated with peripheral white cell count or bone marrow blast cell count, but were positively correlated with platelet count. In B-CLL patients, serum VEGF, MMP-9 and TNF-alpha were significantly higher (p < 0.001 = 0.009, 0.007, respectively) and decreased to near control levels in remission (p>0.05 for all). Serum endostatin levels showed no significant difference at diagnosis and in remission compared to control levels (p>0.05). A significant positive correlation between VEGF, TNF-alpha, MMP-9 and peripheral white cell counts, bone marrow lymphocytic count and platelets count were found. In conclusion, our data suggest that the driving forces of angiogenic factors (VEGF, TNF-alpha and MMP-9) in adult B-ALL appears different from that in B-CLL patients.

We report herein the development of an optical fiber based chemiluminescent immunosensor for detection of the native autoimmune response to GIPC-1, a PDZ containing protein involved in regulation of G-protein signaling. The recombinant protein GIPC-1 was expressed in bacteria, purified, refolded and conjugated to the tip of an optical fiber. A human monoclonal 27.B1 IgM isolated from a breast cancer patient, which targets the GIPC-1 protein, was used for calibration of the immunosensor and was detected down to a concentration of 30 pg/ml. We determined that the fiber-optic immunosensor had a detection limit 50 times lower than chemiluminescent ELISA, and approximately 500 times lower than colorimetric ELISA. In addition, sera from 11 ovarian cancer patients, 22 breast cancer patients and asymptomatic controls were tested for the presence of IgM anti-GIPC-1 autoantibodies in their serum using the two methods. The immunosensor assay detected 54% and 77% GIPC-1 positive sera within ovarian and breast cancer patients, respectively, as compared to chemiluminescent ELISA, which only detected 18% and 27%, respectively. We envision that this immunosensor may serve as a diagnostic tool for screening women for ovarian and breast cancer at an early stage, thus increasing their chance of survival.

In this paper, recent concepts in the management of war wounds of the maxillofacial region are described. A brief differentiation is also given between general practice medicine and military medicine.

Mirazid (MZ), an oleo-resin extract derived from Myrrh was reported in several experimental and clinical trails to be safe and effective against other trematodes like schistosomiasis and fascioliasis. This experimental work aimed at investigating the possible efficacy of MZ against heterophyids (Pygidiopsis genata), using praziquantel as a therapeutic control. Results showed that MZ in emulsion form is a promising drug for the treatment of heterophyidiasis, as proved by significant reduction of worm count, overt surface tegumental changes like deformity and erosion of tegumental spines observed by scanning electron microscope (SEM). The effective dose regimen was 500 mg/kg/d for 3 successive days, produced 100% reduction in worm load. The proved efficacy of the drug, together with reported low toxicity, relative to praziquantel, favours its use as a natural new alternative therapy for the treatment of human heterophyidiasis.

Apoptosis is the primary mechanism through which most chemotherapeutic agents induce tumor cell death. The balance in the expression of pro (Fas/CD95) and anti-apoptotic protein (Bcl-2) may control the response of leukemic cells to chemotherapy and subsequently affect the patient's prognosis. The aim of this study was to determine the levels of Bcl-2 and Fas expression on blast cells from patients with acute leukemia and to correlate the degree of expression to the clinical and laboratory prognostic factors and the patient's outcome. Forty newly diagnosed patients with acute leukemia (16 ALL, 24 AML) were included in the study. Ten normal subjects of matched age and sex were studied as a reference control group. The degree of Bcl-2 and Fas expression on acute leukemia blast cells were assessed before the start of therapy and on mononuclear cells after 1 year of follow up, using flow cytometry. The degree of Bcl-2 and Fas expression were significantly higher in AML (P<0.01,<0.05, respectively) and ALL (P<0.01, <0.05, respectively) as compared to controls. The expression of Fas and Bcl-2 was related to FAB type with the highest Bcl-2 and lowest Fas expression in M5 and T-ALL (P<0.01, for all). In ALL, patients responding to induction chemotherapy revealed lower Bcl-2 and higher Fas expression when compared to non-responders (P<0.05). In contrast, in AML the difference between responders and non-responders to induction chemotherapy regarding Bcl-2 and Fas expressions was not statistically significant (P>0.05). Bcl-2 and Fas expression were significantly elevated in the relapsed acute leukemia group (in both AML and ALL) when compared to those in remission (P<0.01, <0.05, respectively). Bcl-2 and Fas expression at diagnosis was not significantly different when those surviving were compared to the group who had died, either in the ALL or AML groups (P>0.05). Bcl-2 expression was significantly correlated to bone marrow blast cell counts (R=0.6, P<0.01), blast cell distribution ratio (R=0.4, P<0.05) and lymphadenopathy (R=0.33, P<0.05). Whereas Fas expression was significantly correlated to bone marrow blast cell counts (R=0.52, P<0.01). In conclusion, assessment of Bcl-2 and Fas expression at diagnosis in acute leukemia (1) could predict responsiveness to induction chemotherapy in ALL but not in AML group but (2) could not predict patients out come both in ALL and AML groups., (Copyright 2004 Taylor and Francis Ltd.)

Occurrence, constituents and medicinal use of myrrh, obtained from the stem of different Commiphora species are reviewed. The constituents of the volatile oil, the resin and the gum are outlined in detail. Myrrh has considerable antimicrobial activity and is medicinally used in a variety of diseases.

Unlabelled: The aim of this study was to assess circulating soluble L (sL) and soluble E (sE) selectins adhesion molecules in acute myeloid leukemia (AML) blasts in order to evaluate their clinical significance. Fifty patients with AML (4 M0, 8 M1, 16 M2, 5 M3, 7 M4, 6 M5, 4 M6) were included in this study. sL and sE selectins were evaluated at diagnosis, remission and in relapsed patients; whole membrane expression of L and E selectins by AML blast was investigated only at diagnosis. In addition, 15 normal persons were studied as a control group. sL and sE selectins were significantly higher in AML patients at diagnosis when compared to controls (P<0.01), but less at remission (P<0.01). Furthermore, elevated sL and sE selectin levels were detected in patients with AML at relapse. sE and sL selectins were significantly higher in AML patients with extramedullary infiltration as compared to patients without extramedullary disease (P<0.001). Membrane expression of L selectin was positive in 20% of AML patients. However, none of the patients showed significant E selectin expression. Patients with higher sE and sL selectins at diagnosis have high probability of relapse compared to those with normal levels (P<0.01 and <0.001, respectively). The overall relapse predictability of sE and sL selectins was 84%. Moreover, patients with higher sE and sL selectins levels had shorter event free survival than patients with lower levels (P<0.001 for both). The overall mortality prediction using sE, sL, and cellular L selectin was 96%., In Conclusion: (1) AML blast cell express and release sL selectins but not sE selectin, (2) sE and sL selectins and cellular L selectin may be useful prognostic markers in evaluating AML patients at diagnosis.

Schistosomiasis is a widespread helminthic disease. Treatment of schistosomiasis is based on chemotherapy with praziquantel, which is the drug of choice. Since resistance to praziquantel has been demonstrated, alternative drugs must be considered. Myrrh is an oleo-gum resin from the stem of the plant Commiphora molmol. This study was carried out on 204 patients with schistosomiasis. The drug was given at a dose of 10 mg/kg of body weight/day for three days, and induced a cure rate of 91.7%. Re-treatment of cases who did not respond with a dose of 10 mg/kg of body weight/day for six days gave a cure rate of 76.5%, increasing the overall cure rate to 98.09%. The drug was well tolerated, and side effects were mild and transient. Twenty cases provided biopsy specimens six months after treatment and none of them showed living ova.

Myrrh (from the stem of the Commiphora molmol tree) is an oleo gum resin that may prove efficacious for the treatment of fascioliasis. We studied 7 patients who were passing Fasciola eggs in their stools and treated them with myrrh. The drug (a formulation consisting of 8 parts of resin and 3.5 parts of volatile oils, all extracted from myrrh) was given in a dose of 12 mg/kg per day for 6 consecutive days in the morning on an empty stomach. Patients were followed for 3 months. The therapy proved to be effective, with pronounced improvement of the general condition and amelioration of all symptoms and signs. A dramatic drop in the egg count was detected at the end of treatment. Eggs were no longer detectable in the feces 3 weeks after treatment and after a follow-up period of 3 months. High eosinophilic counts, elevated liver enzymes, and Fasciola antibody titers returned to nearly normal. No signs of toxicity or adverse effects were observed. We conclude that the formulation of myrrh is safe, well tolerated, and effective for treating fascioliasis.

Effects of the botanical extract (myrrh), Commiphora molmol, and the sublethal treatments of profenofos/chlorofluazuron, fenvalerate and pyriproxyfen on the larvae of S. littoralis were investigated. The results showed that myrrh induced the highest activity after 7 days of treatment with concentration of 10000 ppm and the percentage of mortality reached 44.4%. The chemical insecticide profenofos/chlorofluazuron appeared to be the most effective treatment, giving a mortality of 54% after one day of treatment with a concentration of 100 ppm. Different treatments showed adverse effects on pupation, emerging adults and larval duration. The highest concentration of myrrh (10000 ppm) induced 35% pupation. No pupa was obtained with profenofos/chlorofluazuron while fenvalerate and pyriproxyfen gave 13.3% at 50 ppm. At 10000 ppm of myrrh, 25% adult was emerged, also fenvalerate and pyriproxyfen decreased the emerging moth to 13.3% at 50 ppm. For control there was no larval mortality at 7 days and the percentages of pupation and adult emergence were 90%. Bioassays were also conducted to test the joint action of myrrh applied in binary mixtures with each chemical insecticide on Spodoptera larvae. Results of the bioassay of mixtures indicated antagonistic effects on larval mortality. However, combination of myrrh with profenofos/chlorofluazuron showed additive effect. Also, the degree of pupation and emerging moth varied considerably when myrrh combined with the chemical insecticides. The present work shows the strong efficacy of the botanical extract (myrrh) which could be used alone or in combination with sublethal doses of certain insecticides to control the cotton leafworm.

The present study was conducted to reveal the pattern of different gastrointestinal malignant neoplasms in Alexandria in the last decade (1987-1996). All registered cases of GIT cancers in Alexandria. Main University Hospital in the last decade were included in the study. The results revealed that the total number of cases was 2184, 58.6% were males and 41.4% were females. The mean age of registered cases was significantly older among males than females (t = 2.43). The highest percentage (47.2%) of cases were in the age group (40- < 60 years). Less than quarters (73.3%) of the total cases have had malignant neoplasms of digestive organs and 26.7% have had malignant neoplasms of lips, oral cavity and pharynx. Of the latter category cancer pharynx came first in both sexes (49.9%) with the youngest mean age (45.65 +/- 15.79 years), followed by cancer tongue (24.9%) with the oldest mean age (58.56 +/- 12.4). Among cases of malignant neoplasms of digestive organs, cancer colon came first in both sexes (26.9%) with the youngest mean age (44.11 +/- 14.08 years). Cancer gall bladder came last (1.2%) with the oldest mean age (55.80 +/- 10.20 years). Over the last decade trend of malignant neoplasms of colon, rectum, liver and pancreas were increasing while the reverse was observed for cancer oesophagus and stomach. So it is necessary to plan for GIT cancer control programme.

Eight million new cases of tuberculosis are merging annually, worldwide, of which an estimated three million are dying. The quality of medical care rendered by chest clinics (dispensaries) to tuberculous patients is crucial. The present study was conducted in order to assess quality of medical care rendered to tuberculous patients in all chest clinics in Alexandria (n=7). To achieve this aim, three checklists were developed in relation to the three dimensions of medical care, namely, structure, process of care and outcome. They were validated and rated by ten medical experts working in the field of tuberculosis and chest diseases. Accordingly for the process of care, each item was scored using weighted scores for physicians' performance. Unit weighted scoring was also used for physicians, nurses, as well as social workers. Direct observation was conducted for assessment of structure and process of care rendered by physicians, nurses and social workers. On the other hand, outcome was measured by cure or treatment completion rate, treatment failure rate, defaulter rate, as well as death rate. The results revealed that percentage of recommended structure items ranged between 77.8% and 94.4%. Regarding process of care, it was found that the overall weighted physicians' performance index (PPI) expressed in percentage was 36.97+/-13.65%, while the mean unit weighted PPI was 35.26+/-13.5%. For the different areas of care, the mean weighted and unit weighted PPI, respectively, were 27.86+/-20.83% and 28.6+/-21.7% in history taking, 54.65+/-11.92% and 42.83+/-13.83% for examination, 31.64+/-19.61% and 37.10+/-19.40% for educating patients, while it was 36.36+/-16.0% and 37.90+/-16.20% for measures applied to contacts. Moreover, assessment of nurses and social workers' performance revealed that they had carried out 91.86% and 86.60% of their recommended activities, respectively. Outcome indices among the different clinics showed that cure or treatment completion rate ranged from 47.48% to 81.51%, while treatment failure rate ranged between 1.71% and 11.54%. On the other hand, the defaulter rate showed a minimum of 13.70% and a maximum of 44.86%. From the present study it could be recommended that quality of medical care in chest clinics should be emphasized specially as regards process of care given by physicians.

The present study was conducted in Hail General Hospital, in Kingdom of Saudi Arabia, over six months period starting from December 1994. All notified cases of nosocomial infections were taken into consideration. Cases who satisfied the definition and criteria of nosocomial infection were included in the study (n = 105). Data were abstracted from the special routine monthly resorts to the General Directorate of Health Affairs. The results of the present study revealed that invasive procedures were conducted for the majority of cases (81.9%). The most common site of infection was urinary tract (36.6%), followed by respiratory and wound infection (23.8% and 22.8% respectively), while other sites accounted for the remaining part of the sample (16.8%). Out of the culture positive cases (n = 101) gram negative bacteria represented 85.15% of cases where the most common ones were Klebsiella pneumonia and pseudomonas. Bivariate analysis revealed a significant linear association between invasive procedures and age (Mantel Hanszel test = 17.37). Moreover, invasive procedures were found to be significantly related to the occurrence of gram negative infection (chi2 = 4.77). Multiple regression analysis, for factors affecting length of hospital stay, showed that age and presence of host factors lowering host resistance had significant effect in prolonging the duration of stay among cases.

Childhood deafness interferes with the cognitive development of the child, so it is considered a major handicap. The present work was carried out to reveal possible risk factors of deaf-mutism and the magnitude of each. The case control design was chosen as a research methodology. A 50% sample of deaf-mute pupils at the primary level were selected at random from each of the two governmental schools for the deaf-mutes in Alexandria (boys=96, & girls=76). A control group chosen at random from a main stream governmental school and matched by age and sex of the pupils as well as with education and occupation of the father. Matching was carried out at the sampling phase, pairing each case to its control. Data were collected by interviewing the mothers using an interviewing schedule. Matched analysis was carried out where pairing of cases and controls was retained. The likelihood estimate of Odds ratio conditional on the number of discordant pairs was estimated using McNemer's test. The 5% level was chosen as the level of significance. The study revealed 172 deaf-mute pupils. Their mean age was 9.48+/-1.981 years. Boys outnumbered girls (55.8% and 44.2% respectively). In 59.4% parents were cousins. Deafness was first noticed at 6 to 60 months of age with a mean of 14.70+/-10.2 months. Most fathers and mothers were illiterate (48.84% and 61.63%). Heredity was a risk factor, where 84.82% of cases had a positive family history compared to none of the controls. Moreover, in case of consanguinity the Odds ratio=5.60. Acquired deafness constituted the second important group of all causes of deafness. Meningitis featured as the most important cause of acquired deafness with an estimated relative risk of 18.5, followed by fever (Odds ratio=4.67), then repeated attacks of acute tonsillitis and ear disease where the case control percent difference was 8.72% and 4.65% respectively.

IgG and IgM anticardiolipin antibody (Ab) concentrations were determined in serum samples of 48 children with end-stage renal disease (ESRD) on haemodialysis using ELISA technique in an attempt to analyse their possible role in the occurrence of thrombosis of the vascular access. Ten normal healthy children were studied as a control group. The positivity of anticardiolipin Ab isotypes both IgM and IgG was high in children with ESRD on haemodialysis. Children with positive anticardiolipin Ab had significantly higher incidence of prior thrombosis of vascular access. Also, these antibodies should be considered as markers of high risk for fistula thrombosis.

One high-performance liquid chromatographic (HPLC) and two thin-layer chromatographic (TLC) methods are proposed for the determination of colchicine in crude drugs and pharmaceutical preparations. The TLC scanner method is based on measurement of the absorbance of the separated colchicine spot; alternatively, after scraping the spot from the plate and elution the absorbance can be measured spectrophotometrically. The HPLC assay was carried out isocratically on a reversed-phase column using MeOH-H2O (60 + 40). The recoveries were 99.2 +/- 1.23, 99.1 +/- 1.12 and 99.1 +/- 2.01% for the TLC scanner, spectrophotometric and HPLC methods, respectively. The methods were shown to be sensitive and specific and can be used as an alternative to the pharmacopoeial methods having been applied to the determination of colchicine in corms of Merendera persica and in three pharmaceutical preparations.