Bone health in pediatric transfusion-dependent beta-thalassemia: Circulating osteoprotegerin and RANKL system.

INTRODUCTION: While the mechanism of bone disease in thalassemia is multifactorial and still under investigation, the receptor activator of nuclear factor kappa B (RANK), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) have pivotal roles in regulating bone metabolism. This study aimed to measure RANKL and OPG serum levels, and to detect the incidence of RANKL rs9533156, OPG rs2073618, and OPG rs2073617 genotypes in pediatric ß-thalassemia patients and to assess their relation to bone mineral density. METHODS: Sixty patients with transfusion-dependent ß-thalassemia (TBT) patients ages 5 to 14 years were included, and 60 healthy, age- and sex-matched volunteers contributed as a control group. The patients were scanned for bone mineral density. RESULTS: The mean of spine dual-energy X-ray absorptiometry (DXA) Z-score in patients was -1.66 ± 1.02 standard deviation (SD). Twenty-four of them had low spine DXA Z-scores. The patients showed significantly lower OPG levels and OPG/RANKLs ratios than the control group (3.28 ± 9.11 ng/ml and 11.38 ± 14.93 ng/ml, and 0.01 ± 0.03 and 0.07 ± 0.09, respectively). The RANKL SNP rs9533156 TC heterozygous genotype was detected more with statistical significance in patients than controls. The incidence of OPG rs2073618 and OPG rs2073617 genotypes were 2.3 times and 1.9 times more frequent in patients than controls, respectively. CONCLUSION: The RANK/RANKL/OPG system may have an important role in regulating bone metabolism in TBT patients, although further studies are needed to clarify its role.

A genomics approach to male infertility.

PURPOSE: Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility. METHODS: Patients with severe oligospermia and nonobstructive azoospermia were investigated using exome sequencing (ES) in parallel with the standard practice of chromosomal analysis. RESULTS: In 285 patients, 10.5% (n = 30) had evidence of chromosomal aberrations while nearly a quarter (n = 69; 24.2%) had a potential monogenic form of male infertility. The latter ranged from variants in genes previously reported to cause male infertility with or without other phenotypes in humans (24 patients; 8.4%) to those in novel candidate genes reported in this study (37 patients; 12.9%). The 33 candidate genes have biological links to male germ cell development including compatible mouse knockouts, and a few (TERB1 [CCDC79], PIWIL2, MAGEE2, and ZSWIM7) were found to be independently mutated in unrelated patients in our cohort. We also found that male infertility can be the sole or major phenotypic expression of a number of genes that are known to cause multisystemic manifestations in humans (n = 9 patients; 3.1%). CONCLUSION: The standard approach to male infertility overlooks the significant contribution of monogenic causes to this important clinical entity.

Spectrum of Ovarian Incidentalomas: Diagnosis and Management.

Incidental ovarian lesions are asymptomatic lesions that are accidentally discovered during a CT or MRI examinations that involves the pelvic cavity or during a routine obstetric ultrasound study. Incidental ovarian masses are usually benign with a very low risk of malignancy yet underlying malignant pathology may be discovered during the diagnostic work-up of these lesions. Suspicion of malignancy is directly correlating with the increase in the patient's age, the increase in the size of the lesion, the presence of the solid components or thick septa and a high color scale of the ovarian mass. Following standard reporting and management protocols are essential to choose the proper work-up of these lesions to avoid unnecessary additional imaging and operative intervention. In this article, we will provide a review of the characteristic imaging features of some incidental and yet commonly encountered ovarian lesions. We will also summarize the recently published algorithms that are important for consistent reporting and standard management of these lesions.

Prenatal prediction of respiratory distress syndrome by multimodality approach using 3D lung ultrasound, lung-to-liver intensity ratio tissue histogram and pulmonary artery Doppler assessment of fetal lung maturity.

OBJECTIVE: Studying the correlation of different lung parameters, using three-dimensional ultrasound (3D US) with fetal lung maturity (FLM) to predict the development of neonatal respiratory distress syndrome (RDS). METHODS: Three-dimensional ultrasound was done to record the fetal lung volume (FLV), fetal lung-to-liver intensity ratio (FLLIR) and the main pulmonary artery (MPA) blood flow parameters; pulsatility index (PI), resistive index (RI) and acceleration time-to-ejection time ratio (At/Et), to 218 women between 32 and 40 weeks gestational age within 24 h from labor. RESULTS: Of 218 fetuses examined, final analysis was done for 143 fetuses. Thirty eight (26.5%) were diagnosed with RDS. The MPA PI and RI were significantly higher in fetuses diagnosed with RDS compared with those without (2.51 ± 0.33 and 0.90 ± 0.03 cm/s versus 1.96 ± 0.20 and 0.84 ± 0.01 cm/s; p value < 0.001 and <0.001 respectively). MPA At/Et was significantly lower (0.24 ± 0.04 vs 0.35 ± 0.04; p value < 0.001). FLLIR was significantly lower (1.04 ± 0.07 vs 1.18 ± 0.11; p value < 0.001), and the mean FLV was significantly smaller (28.23 ± 5.63, vs 38.87 ± 4.68 cm3; p value < 0.001). CONCLUSION: Main pulmonary artery (PI, RI, At/Et ratio), FLIIR, and mean FLV can be used as reliable predictors of neonatal RDS. ADVANCES IN KNOWLEDGE: 3D ultrasound VOCAL technique, ultrasound tissue histogram and pulmonary artery Doppler are reliable tools for prenatal prediction of fetal lung maturity.

Classification of inflammatory breast disorders and step by step diagnosis.

In this study, the authors proposed a classification of inflammatory breast disorders based on which a practical systematic scheme in diagnosis was applied aiming to differentiate simple forms of mastitis from more complicated and malignant forms. The study population included 197 female patients who were clinically or pathologically diagnosed as having mastitis. All patients underwent Ultrasound examination. Mammography was performed for 133/197 cases. Cases of simple mastitis and periductal mastitis were followed up to ensure complete resolution. Abscess cavities and postoperative collections were drained. Other cases were biopsied to confirm diagnosis and were managed accordingly by their treating physicians. Statistical analysis was performed by the Statistical Package for Social Science. Nominal Data were expressed as frequency and relative frequencies (percentage). Ultrasound and Mammography categorical results were compared using the Pearson Chi Square and Fisher's exact test. Patients were classified into three groups; infectious, noninfectious and malignant mastitis. Simple and malignant forms of mastitis showed many signs in common. The presence of ill defined collections and abscess cavities on ultrasound favored simple over malignant forms of mastitis while extensive skin thickening and infiltrated malignant nodes favored malignant forms. Interstitial edema, edematous fat lobules, abscess cavities, skin thickening seen on ultrasound examination were significantly lower in noninfectious than simple and malignant mastitis. Mammography signs were less discriminating. Diffuse skin thickening and increased density favored malignant mastitis while dilated retro areolar ducts and characteristic calcification patterns favored noninfectious forms. Simple mastitis showed nonspecific signs. Ultrasound examination in mastitis cases shows more specific signs in differentiating between the three forms of mastitis and is useful in monitoring treatment, excluding complications and guide for interventional procedures. Mammography should be performed whenever complicated, malignant and uncommon forms of mastitis are suspected.

Chemerin level and the relation to insulin resistance in chronic kidney disease.

Chemerin has been associated with different components of the metabolic syndrome, including hypertension, hyperlipidemia, and insulin resistance (IR). The aim of this study was to evaluate serum chemerin level in chronic kidney disease (CKD) patients and its relation to IR. This study was conducted on 80 participants who were classified into three groups: Group I (30 CKD patients with mean age 53 ± 12 years), Group II (30 patients with end-stage renal disease on regular hemodialysis with mean age 48 ± 14.8 years) and Group III having 20 healthy age-and sex-matched controls. Serum chemerin level, fasting blood sugar, fasting insulin, HOMA-IR index calculation, urea, creatinine, estimated glomerular filtration rate, total cholesterol, and triglyceride were measured. Body composition was assessed by dual-energy X-ray absorptiometry. In Groups I and II, we found a significantly higher mean chemerin level compared to healthy controls (P <0.001), a highly significant positive correlation between mean chemerin level and the HOMA-IR index [r = 0.56, P <0.001/(r = 0.53, P <0.001)], and a highly significant negative correlation between mean chemerin level and GFR (r = -0.51, P <0.001/r = -0.46, P <0.001). In Group I, there was also a highly significant positive correlation between mean chemerin and systolic blood pressure (r = 0.31, P <0.05), diastolic blood pressure (r = 0.39, P <0.05 and creatinine (r = 0.34, P <0.05). Chemerin might be considered a uremic IR adipokine marker in CKD Stages 3, 4, and 5.

Ovarian cancer screening-ultrasound; impact on ovarian cancer mortality.

Although ovarian cancer (OC) is the most lethal of all female malignancies, debate still exists concerning the benefits and harms of the screening programs and their impact on long-term survival and mortality from the disease. The most widely tested screening strategies have focused on transvaginal ultrasound (TVU) and on algorithms that measure serum levels or interval changes of cancer antigen-125 (CA-125) either individually or in combination. Transvaginal ultrasound can identify size and morphology changes of the ovary that may signal a developing malignancy; yet, it is still accused of having a low specificity. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from OC is still unclear and warrants further validation. In spite of having many published prospective studies, up to-date, none have been able to demonstrate conclusively a reduction in mortality from OC both in the screened general or high-risk population. Data from the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial has not shown survival or mortality benefits in the general population. Most prospective trials have reported a decrease in stage at detection (with the exception of the PLCO trial), thereby allowing treatment to be initiated when the disease is most curable. Research is in progress to develop new diagnostic tests and novel biomarkers, which when used in combination can increase the accuracy and outcomes of screening. In this review article, we will discuss the debate provoked on OC screening programs and the impact of using ultrasound on the reduction of OC-related mortality.

Surface transperineal ultrasound and vaginal abnormalities: applications and strengths.

The role of ultrasound in the assessment of the female pelvis whether using transabdominal/transluminal approach is well established. Little was reported about the use of the superficial transperineal approach that could provide a full assessment of the lower cervix and vagina, which may be overlooked in the standard examinations. The proximity of the probe to the vagina helps not only the detection of organ abnormalities but also proper characterization and differentiation of vaginal masses. . We discuss the diagnostic role of this superficial ultrasound approach in improving the perception and interpretation of the anatomy and different diseases of the vagina.

Diffusion-weighted MR imaging and assessment of ovarian carcinomas with vaginal deposit accidentally detected during pregnancy.

Ovarian cancer during pregnancy is a complex situation that endangers the lives of both the pregnant female and the fetus. We present a 40-year-old pregnant female in the third trimester with bilateral undifferentiated ovarian adenocarcinoma and vaginal metastasis. The case was evaluated by ultrasound and MRI supported with diffusion-weighted sequence.

The relation between dual energy x-ray absorptiometry measurement of body fat composition and plasma ghrelin in patients with end-stage renal disease.

OBJECTIVE: To clarify the role of ghrelin in malnutrition in uremia and its relationship to fat composition using dual x-ray absorptiometry (DXA). METHODS: This is a cohort study including Group I: 60 patients with end stage renal disease 30 on hemodialysis [group IA] and 30 pre-dialysis [group IB] and Group II: 20 controls. This study was carried out in Cairo University Hospital, Kasr Al-Aini, Cairo, Egypt in 2007. Body fat composition (total, differential, and lean body mass) was assessed using DXA, and plasma ghrelin was measured. RESULTS: Ghrelin was significantly higher in hemodialysis and pre-dialysis groups compared to the control group, and higher in hemodialysis group compared to the pre-dialysis group. In hemodialysis, ghrelin was negatively correlated with weight, body mass index (BMI), and truncal fat mass, and positively correlated with serum creatinine. In pre-dialysis, ghrelin inversely correlated with weight, BMI, and truncal fat mass, and positively correlated with serum creatinine, lean body mass. In control, plasma ghrelin showed negative correlation with weight, BMI, truncal fat mass, and body fat mass, and positive correlation with lean body mass. CONCLUSION: Ghrelin was markedly elevated in renal failure due to its decrease in excretion. Negative correlation between ghrelin and fat composition was detected in dialysis patients. Serial evaluation of body fat composition using DXA is recommended for assessment of nutritional status of those patients.

Breast discharge: ultrasound and Doppler evaluation.

BACKGROUND: Nipple discharge causes discomfort and anxiety to many women. Nipple discharge is most commonly associated with endocrine alterations and/or medications. These often result in duct ectasia and/or fibrocystic changes that may lead to discharge from one or several ducts. The most common cause of clinically significant discharge is intraductal growth of the ductal epithelium, due to hyperplasia, micropapillary proliferation, solitary papillomas and/or ductal carcinoma (both in situ and invasive). The aim of the study was to evaluate the role of the gray-scale ultrasound and colour Doppler in the diagnosis of intraductal pathology in patients with nipple discharge. PATIENTS AND METHODS: One hundred & seven patients were included in the study, (age range 23-65years). Standard mammographic views were taken. Ultrasound evaluation was performed for all cases; ductography for 20 cases and ductoscopy for 3 cases. US guided fine needle biopsy was done in 7 cases; microducectomy of affected duct was done in 20 cases and major duct excision in 5cases. Fibro-optic Ductoscopy is performed for 3 cases. RESULTS: Revision of biopsy specimens of 17 cases with intraluminal masses detected by US revealed: Six cases with intraductal carcinoma, intraductal papilloma in 7 cases, 1 case of ductal papillomatosis. Three cases showed atypical cells: Intraductal papilloma with atypia in 2 cases, proliferative hyperplasia with atypia in one case. Eighty eight cases had simple duct ectasia (51 bilateral multiple and 37 focal duct ectasia). No dilated ducts were detected in 2 cases. Fibro-optic Ductoscopy confirmed the presence of intraductal papilloma in one case, carcinoma in one case, no intraductal masses in the third case. A 6 months follow-up was requested for all cases with no detected intra luminal pathology. Ultrasound examination is highly sensitive (100%) but less specific (82.4%) in diagnosis of intraductal pathology. Colour & power Doppler are sensitive (94%) in detecting flow in intraductal echogenic masses to differentiate them from insipissated secretions. Colour and power Doppler raises specificity and diagnostic accuracy to 100%. Ductography is an underused procedure that is sensitive (100%) but less specific (60%) in characterization of intraductal filling defects. CONCLUSION: Ultrasonography is a mandatory complement to mammography in these cases, US guided fine needle biopsy is minimally invasive technique in confirming the diagnosis of suspicious mass. Ultrasound may also be a guide to fibro-optic ductoscope. KEY WORDS: Ductography - Nipple discharge - Intraductal carcinoma - Intraductal papilloma - In situ ductal carcinoma - Invasive ductal carcinoma - Duct ectasia - Breast ductoscopy.

Women Health Outreach Program; a New Experience for all Egyptian Women.

UNLABELLED: The global health community faces a challenge with breast cancer being the most common cause of cancer related death among women around the globe. Since breast cancer's pathogenesis is poorly understood, primary prevention is still a distant goal. Thus secondary prevention through early detection is the only feasible approach at present. With this strong conviction, the launching of the first Egyptian national screening program "Women Health Outreach Program" (WHOP), was announced on October 30th 2007. This project is a government- funded program that offers free breast screening for all Egyptian women above the age of 45 years. In addition to free mammograms, the program gives the participants a chance to be screened for diabetes, hypertension and obesity as well. Positively detected cases are also offered the option of free management. During the period from October 30th, 2007, up to February 9th, 2009, 20, 098 women in Cairo, Alexandria and Suez governorates were screened for breast cancer, diabetes, hypertension and obesity through the program. In this article we will represent the achievements, challenges and services delivered by WHOP. KEY WORDS: Breast cancer - Breast screening - Early detection - Breast biopsy.