Breast cancer in Lebanon. Increased age-adjusted incidence rates in younger-aged groups at presentation: implications for screening and for Arab-American ethnic groups.
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Adult↗
Biomedical subjects
Z Khatib
Publications and source records attributed to Z Khatib.
Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine.
PURPOSE: To assess thiopurine S-methyltransferase (TPMT) phenotype and genotype in patients who were intolerant to treatment with mercaptopurine (MP) or azathioprine (AZA), and to evaluate their clinical management. PATIENTS AND METHODS: TPMT phenotype and thiopurine metabolism were assessed in all patients referred between 1994 and 1999 for evaluation of excessive toxicity while receiving MP or AZA. TPMT activity was measured by radiochemical analysis, TPMT genotype was determined by mutation-specific polymerase chain reaction restriction fragment length polymorphism analyses for the TPMT*2, *3A, *3B, and *3C alleles, and thiopurine metabolites were measured by high-performance liquid chromatography. RESULTS: Of 23 patients evaluated, six had TPMT deficiency (activity < 5 U/mL of packed RBCs [pRBCs]; homozygous mutant), nine had intermediate TPMT activity (5 to 13 U/mL of pRBCs; heterozygotes), and eight had high TPMT activity (> 13.5 U/mL of pRBCs; homozygous wildtype). The 65.2% frequency of TPMT-deficient and heterozygous individuals among these toxic patients is significantly greater than the expected 10% frequency in the general population (P <.001, chi(2)). TPMT phenotype and genotype were concordant in all TPMT-deficient and all homozygous-wildtype patients, whereas five patients with heterozygous phenotypes did not have a TPMT mutation detected. Before thiopurine dosage adjustments, TPMT-deficient patients experienced more frequent hospitalization, more platelet transfusions, and more missed doses of chemotherapy. Hematologic toxicity occurred in more than 90% of patients, whereas hepatotoxicity occurred in six patients (26%). Both patients who presented with only hepatic toxicity had a homozygous-wildtype TPMT phenotype. After adjustment of thiopurine dosages, the TPMT-deficient and heterozygous patients tolerated therapy without acute toxicity. CONCLUSION: There is a significant (> six-fold) overrepresentation of TPMT deficiency or heterozygosity among patients developing dose-limiting hematopoietic toxicity from therapy containing thiopurines. However, with appropriate dosage adjustments, TPMT-deficient and heterozygous patients can be treated with thiopurines, without acute dose-limiting toxicity.
Adolescent↗
Outcome of moderate aplastic anemia in children.
PURPOSE: In order to assist in the management of newly diagnosed children with moderate aplastic anemia (MAA) we reviewed the clinical course and outcome of children with MAA seen at our institution over the past 12 years and compared them with children with severe aplastic anemia (SAA). PATIENTS AND METHODS: MAA was defined as having a hypocellular bone marrow and cytopenia in at least two cell lines not in the severe range. Twelve children met these criteria. Twenty-eight children with SAA were seen during the same interval. Patients with MAA were treated with immunomodulation with antithymocyte globulin and/or cyclosporine if they progressed to SAA. RESULTS: Five patients with MAA progressed to SAA at a median interval of 18 months from diagnosis. The other seven patients required no therapy or only received transfusions for < or = 6 months after diagnosis. The survival of the patients with MAA was significantly better than that of patients with SAA treated with immunomodulation (p = 0.022). All patients with MAA are alive at a median follow up of 7 years and are transfusion independent; only one patient currently receives therapy. Residual hematologic abnormalities in children with MAA included thrombocytopenia, leukopenia, and macrocytosis. CONCLUSIONS: In this small series of children with MAA the outcome was excellent and significantly better than in patients with SAA; more than half recovered with minimal or no therapy. Patients who progressed to SAA responded well to treatment. A larger prospective study is needed to conclusively define the natural history of MAA.
Adolescent↗
Acquired progressive lymphangioma.
Acquired progressive lymphangioma is rare and can histologically mimic well-differentiated angioendothelioma. In a 9-year-old boy with acquired progressive lymphangioma, we demonstrated that the neoplasm consists of at least a vascular component and a smooth muscle component. The presence of type IV collagen around many vascular channels suggests that an intermediate stage of differentiation between blood vessels and lymphatics may be present. Our findings indicate that acquired progressive lymphangioma is most likely a complex hamartoma composed of vascular channels and smooth muscle.
Basement Membrane↗
Juvenile progressive systemic sclerosis: report of five cases.
Five cases of juvenile progressive systemic sclerosis (SSc) are reported (4 girls and 1 boy). The age of onset of the disease ranged from 4 to 13 years. The clinical features included Raynaud's phenomenon present in 4 of 5 cases; hyperpigmentation, skin tightening and contractures of the large joints were noted in all 5 cases. One patient initially diagnosed as having eosinophilic fasciitis developed SSc 3 months later. Another patient was diagnosed initially as having juvenile rheumatoid arthritis. There was one case of pulmonary fibrosis and another of mild restrictive lung disease. Two cases of esophageal and intestinal hypomotility were reported. Scleroderma nephropathy was absent in all 5 cases.
Adolescent↗
Cytogenetic and molecular characterization of a congenital mesoblastic nephroma.
A newborn baby boy was diagnosed with the mixed form of congenital mesoblastic nephroma (CMN) representing both classic and cellular histology features in the renal tumor. Additionally, the patient had skin and bone lesions consistent with multifocal involvement of a generalized infantile fibromatosis (IFS). Both skin and bone lesions were distinctly different from CMN and did not represent metastasis. The primary tumor cell line (MCH-MN-1), established from the resected right kidney tumor, had a diploid DNA content. Cytogenetic studies revealed deletion on the long arm of chromosome 3 (q21q24) and duplication on the short arm of chromosome 11 (p15). MCH-MN-1 cells expressed ETV6-NTRK3 gene fusion transcripts, characteristic of cellular and mixed forms of CMNs. The cells had high p21 and low Bax mRNA expression in the reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The high level of proliferative marker (Ki67) mRNA expression correlated well with the pluripotent nature of MCH-MN-1 in tissue culture (cell doubling time = 12.4 h). Our results showed that MCH-MN-1 might be a good model cell line for investigations on mesoblastic nephroma.
Chromosome Deletion↗
Expression of apoptosis, cell proliferation, and drug resistance genes in pediatric Wilms' tumors.
The expression of genes associated with apoptosis, cell proliferation and drug resistance in tumor cells was investigated in two pediatric Wilms' tumor patients (MCH-WT-1 and MCH-WT-3) for their association with cell cycle, daunorubicin accumulation and clinical data. DNA content, cell cycle and drug accumulation were analyzed immediately after surgery by flow cytometry and mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Primary cell cultures were established from tumor specimens and tumor cells in both cases showed epithelial morphology. Although cell proliferation markers (Ki67 and PCNA) were expressed in both cases, MCH-WT-3 showed higher levels of mRNA expression, which corresponded, with metastatic behavior of the tumor in the patient. While p53 and p21 mRNAs were expressed at low levels in MCH-WT1, MCH-WT-3 showed high levels of p21 mRNA only. The increased expression of cyclin kinase inhibitor (p21) in MCH-WT-3 compared to MCH-WT-1 correlated with a higher percentage of G0/G1 cell population in the tumor specimen. Despite the expression of multidrug resistance markers (MDR1 and LRP) in MCH-WT-1, flow cytometric analysis showed tumor cell populations with very low and high daunorubicin accumulation and with the absence of any effect for verapamil and dipyridamole on daunorubicin accumulation of tumor cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
[The use of 3rd-generation antacid preparations for the treatment of patients with nonulcerous dyspepsia and peptic ulcer complicated by reflux esophagitis].
In the present investigation on the treatment of patients with nonulcerous dyspepsia and peptic ulcer, hiatus hernia complicated with reflux esophagitis, a mechanism has been studied of the action of topalkan, a 3rd generation aluminium-magnesium antacid, that involves not only its antacid properties but in an even greater degree the availability of alginic acid in its formula which has antipeptic and protective effect with respect of the mucous membrane of the stomach and esophagus, and provides, together with the magnesium salts, a floating layer of the preparation in the stomach. In grave course of nonulcerous dyspepsia (preulcerous condition) and peptic ulcer complicated by reflux disease of the esophagus topalkan was used in combination with present-day antisecretory preparations pyrenzepine or H2-blockaders of histamine receptors capable of enhancing the antisecretory effect of topalkan as well as endowed with cytoprotective properties with respect of the mucous membrane of the stomach and duodenum promoting healing of erosions and healing and scarring of ulcerous defects.
Aluminum Hydroxide↗
[The prevention of stress-related postoperative and drug-induced erosive-ulcerative lesions of the upper digestive tract].
Based on the studies made in 84 patients with calculous cholecystitis and 12 patients with calcifying pancreatitis, an efficiency was shown of infusional administration of pyrencepine or ranitidine to prevent stress postoperative erosive-and-ulcerous lesions of gastroduodenal zone. Gastrocepine is shown to be superior to ranitidine and can be withdrawn without a maintenance dose, as well as becouse its cytoprotective effects with respect of the gastric and duodenal mucosa.
Anti-Inflammatory Agents↗
[New aspects in the use of pirenzepine for the treatment of digestive organ diseases].
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Acute Disease↗