Clinical Implication of Toll-Like Receptors (TLR2 and TLR4) in Acute Myeloid Leukemia Patients

Backgrounds: Toll-like receptors 2; 4 (TLR2;4) are an essential component of the innate immunity and play an important role in immune-surveillance and immune response to various microorganisms. This study aimed to investigate the association between TLR2 and TLR4 polymorphism and the risk of acquiring severe infections, and impact on AML patient’s outcome. Subjects and methods: Using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP); we analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) in 120 AML patients and 100 healthy control subjects. Results: No significant differences in genotype or alleles frequency between healthy controls and AML patients regarding TLR2 Arg753Gln, TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms (P>0.05 for all). Neutropenic fever was detected in 110 out of 120 (91.7%) of the studied AML patients. The sepsis and pneumonia were identified in 20 out of 120 patients (16.7%). The incidence of sepsis was associated with TLR2 Arg753Gln: AG genotypes, A allele and TLR4 Asp299Gly: CT genotype and C allele as compared to other genotypes and alleles. Moreover; TLR2 (Arg753Gln) GG polymorphisms significantly associated with shortest overall survival (OS) and shortest disease-free survival (DFS); while TLR4 polymorphisms affect the DSF only but not OS. In AML patients TLR2 Arg753Gln gene polymorphism is associated with high susceptibility to sepsis and TLR4 (Asp299Gly and Thr399Ile) gene polymorphism is associated with high susceptibility for both pneumonia; and sepsis. Conclusion: TLR2 Arg753Gln (AG; GG genotype) polymorphisms are associated with shortest OS and DFS. Moreover; significant association between TLR2 polymorphisms, TLR4 Arg753Gln polymorphisms and risk of severe infections in AML patients was documented.     

Mucinous adenocarcinoma arising from chronic perianal fistula

Perianal mucinous adenocarcinoma is a rare tumour which may be associated with long‐standing chronic perianal sepsis. Early diagnosis is challenging and is based on a high index of clinical suspicion and specific histological features. Definitive treatment is surgical, in the form of an abdomino‐perineal resection. We hereby describe a case of a perianal mucinous adenocarcinoma arising from long‐standing recurrent perianal fistula and complement this with a brief review of the literature pertaining in particular to the management of this condition.     

Age trends in femur stresses from a simulated fall on the hip among men and women: evidence of homeostatic adaptation underlying the decline in hip BMD.

Age trends in proximal femur stresses were evaluated by simulating a fall on the greater trochanter using femur geometry from hip DXA scans of 5334 white men and women in the NHANES III survey. Expansion of femur outer diameter seems to counter net bone loss so that stresses remain similar across age groups, but stresses are higher in older women than in older men. INTRODUCTION: The age decline in hip BMD is caused by both bone loss and expansion of outer diameter that increases the region size over which mass is measured in a DXA scan. Because expansion has an opposing effect on structural strength, it may be a homeostatic adaptation to net bone loss to ensure that load stresses are kept within a narrow range. MATERIALS AND METHODS: Age trends in femur stresses were evaluated with an engineering beam simulation of a fall on the greater trochanter. Hip geometry was extracted from hip DXA scans using the Hip Structure Analysis (HSA) software on 2613 non-Hispanic white men and 2721 women from the third National Health and Nutrition Examination Survey (NHANES III). Using body weight as load, stresses were computed on the inferior-medial and superior-lateral femur neck at its narrowest point and the medial and lateral shaft 2 cm distal to the midpoint of the lesser trochanter. Stresses and the underlying geometries in men and women >50 years oaf age were compared with those 20-49 years of age. RESULTS: Compared with men <50 years of age, stresses in older men were 6% lower on both surfaces of the shaft, 4% lower on the inferior-medial neck, and not different on the superior-lateral neck. In women >50 years of age, stresses on the proximal shaft and inferior-medial neck remained within 3% of young values but were 13% greater on the superior-lateral neck. Neck stresses in young women were lower on the superior-lateral than the inferior-medial neck, but lateral stress increased to the level on the medial surface in older women. Stresses were higher in women than in men, with a greater gender difference in those >50 years of age. CONCLUSIONS: We conclude that femur expansion has a homeostatic effect in men and women that opposes bone loss so that stresses change little with age. Because expansion preserves stresses with progressively less bone mass, the process may reduce structural stability in the femoral neck under fall conditions, especially in the elderly female.     

“Inorganic and Organometallic Clusters and Polymers: Syntheses and Applications” Symposium

Conference Reports: This section contains reports on topical conferences. Reports are usually written at the request of the editorial office, but unsolicited contributions are also welcome. Suggestions should be sent to the editorial office of the Macromolecular journals, preferably by E‐mail to macromol@wiley‐vch.de.     

Recurrent pregnancy loss due to familial and non-familial habitual molar pregnancy.

OBJECTIVES: To present a series of women with recurrent molar pregnancies, including rare familial cases, and discuss etiology and treatment options. METHODS: We performed a detailed clinical evaluation and pedigree analysis of five Egyptian women with recurrent pregnancy loss due to molar pregnancy. RESULTS: The women had a history of four to nine consecutive hydatidiform moles but of no viable pregnancies. Two of the women had molar pregnancies with different husbands who themselves had viable offspring from previous wives; and three of them, who belonged to a family with extensive intermarriage, had a pedigree consistent with an autosomal recessive maternal-effect mutation. CONCLUSIONS: Recurrent pregnancy loss due to habitual molar pregnancy is uncommon and familial cases are extremely rare. The etiology of this disorder is not well understood but likely results from a maternal-effect mutation. Management options are limited, especially for couples who desire to have their own genetic offspring.     

Prefabrication of bone by vascular induction: an experimental study in rabbits.

The various methods of prefabricating flaps include vascular induction through staged transfer; pretransfer delay, expansion, and grafting; the use of alloplastic materials; and tissue bioengineering. In this experimental study, vascular induction was used to provide an axial vascular pedicle to randomly nourished tissue. Twenty-six New Zealand rabbits, ages and weights ranging between 6 months-1 year and 1.5-3.5 kg, respectively, were used. The sex difference was not considered. The deep inferior epigastric artery and vein were used to carry blood and were placed into a segment of femur to prefabricate the bone. Four weeks later, the viability of the segment of bone prefabricated by new axial pedicle was shown by scintigraphic study, and the new axial pedicle was ready for free transfer.     

Diagnostic utility of serum dipeptidyl peptidase (DPP- IV) /CD26 as a serum marker in Egyptian patients with colorectal cancer

ABSTRACT

Background

Colorectal cancer (CRC) is considered a major cause of morbidity and mortality in Egypt. Colonoscopy is the standard for detection of lesions. The combination of screening methods is effective. Decrease and loss of DPP-IV/CD26 expression and activity are found in microenvironments of specific tumors which are related to impaired immune functions.     

Expression of luminal and basal cytokeratins in human breast carcinoma

We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any. Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14. Additionally, assessment of alpha-smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed. The vast majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age. In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age. Multivariate analysis showed that CK 5/6 was an independent indicator for relapse free interval. We were able to subgroup the cases into four distinct phenotype categories (pure luminal, mixed luminal/basal, pure basal and null), which had significant differences in relation to the biological features and the clinical course of the disease. Tumours classified as expressing a basal phenotype (the combined luminal plus basal and the pure basal) were in a poor prognostic subgroup, typically ER negative in most cases. These findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance.