Manal Kamal

Clinical significance of serum concentration of anti-Müllerian hormone in obese women with polycystic ovary syndrome

In the human ovary, expression of anti-Müllerian hormone (AMH) is detected primarily in granulosa cells of preantral and small antral follicles. The aim of this study was to compare serum AMH measurements in obese women with polycystic ovary syndrome (PCOS) with those in obese normo-ovulatory women and to evaluate the role of AMH as a predictor of ovulation induction by clomiphene citrate compared to FSH. Sixty-eight obese women with PCOS were compared to 17 normoovulatory obese women. All women had a body mass index greater than 30 kg/m(2). Women with PCOS received clomiphene citrate (150 mg/day) for 5 days starting from day 3 of cycle and were subdivided into responsive and non-responsive groups. There was a significant difference in AMH concentration between women with PCOS and the control group (P < 0.05) and also between women with PCOS who responded to clomiphene citrate and those who did not (P < 0.01). A value of 1.2 ng/ml AMH could be used to predict response to clomiphene citrate in obese women with PCOS (sensitivity 71%, specificity 65.7%). AMH production increases in women with PCOS compared to controls. AMH measurement could also be useful in the prediction of ovarian response to clomiphene citrate.

Do Serum Angiopoietin-1, Angiopoietin-2, and Their Receptor Tie-2 and 4G/5G Variant of PAI-1 Gene Have a Role in the Pathogenesis of Preeclampsia?

Objective To evaluate whether serum angiogenesis markers such as angiopoietins (Ang-1, Ang-2) and their receptor (Tie-2) are altered in women with preeclampsia. We also performed genotyping to determine if the 4G/5G genotypes of −675 PAI-1 gene may play a role in the pathogenesis of preeclampsia. Materials and Methods Sixty-eight pregnant women with preeclampsia were compared to 35 normotensive pregnant women and 24 normotensive nonpregnant women in a cross-sectional study. Using enzyme-linked immunosorbent assay, levels of serum Ang-1 and Ang-2, and Tie-2 were measured. A single base pair insertion/deletion 4G/5G polymorphism of the PAI-1 gene was determined by polymerase chain reaction. Results Serum levels of Ang-1 and Tie-2 were significantly different among the study groups (P = 0.001 and P = 0.025, respectively) being lower in the preeclamptic group. Positive significant correlation was found between Ang-2 and Tie-2, (r = 0.26, P = 0.024). The frequency of the genotypes (4G/5G, 4G/4G, and 5G/5G) differed among the groups (P = 0.001). Also, the mean of systolic and diastolic blood pressures differed significantly according to the PAI-1 genotype being higher in those bearing the 4G allele; P = 0.04 and P = 0.023, respectively. Conclusion Sera Ang-1 and Ang-2, and Tie-2 as well as variants of 4G/5G of PAI-1 polymorphism have positive implications in the pathogenesis of preeclampsia.

Assessment of male serum anti-Mullerian hormone as a marker of spermatogenesis and ICSI outcome

Objective. To assess serum anti-Mullerian hormone (AMH) as a marker of spermatogenesis among fertile and infertile males, as well as its relation to ICSI outcome. Methods. A total of 77 male partners of infertile couples seeking infertility treatment were recruited for this study. They were classified according to the WHO criteria of semen analysis into three groups; azospermia, oligospermia, and normal. All participating patients had a serum assay of the level of AMH. Thirty-three couples out of the previously mentioned 77 couples underwent controlled ovarian stimulation and ICSI. Results. There were 41 patients with azospermia, 14 patients with oligospermia, and 22 patients with normal count. There was no significant difference among the three groups regarding the AMH levels. There was no significant correlation between the AMH levels from all patients and the sperm concentration (rho = 0.03, p = 0.82). Among patients who underwent ICSI, there was no significant correlation of the AMH with the age, sperm concentration, fertilisation percent or number of embryos. The age of male partners was significantly correlated with sperm concentration, fertilisation percent and the total number of embryos. In the logistic regression model used, serum AMH had no significant relation to clinical pregnancy. Conclusion. Male serum AMH levels are not indicative of spermatogenesis and cannot differentiate between fertile and infertile males. Serum AMH levels were not predictive of ICSI outcome as well.

Matrix Metalloproteinase-9 and Recovery of Acute Ischemic Stroke

BACKGROUND Stroke outcome can be predicted by clinical features, biochemical parameters, and some risk factors. Matrix metalloproteinase-9 (MMP-9) is involved in various stages of stroke pathology. MMP-9 inhibitors are potential stroke therapeutic agents. Little is known about the relation between MMP-9-after the acute stage-and clinical recovery. OBJECTIVE The study aimed to investigate the serum level of MMP-9 at stroke onset as predictor of stroke outcome and the relation between the level of MMP-9 after 30 days and stroke recovery. METHODS The National Institutes of Health Stroke Scale, modified Rankin Scale, and serum level of MMP-9 were assessed in 30 patients with acute ischemic stroke during the first 24 hours of onset and then a month later. None of the patients received thrombolytic therapy. Thirty normal volunteers of matched age and sex were included in the control group. RESULTS The serum level of MMP-9 at stroke onset was independently positively correlated with stroke outcome. The serum level of MMP-9 30 days after stroke onset was positively correlated with initial stroke severity and outcome, as well as with clinical recovery. CONCLUSION Higher serum level of MMP-9 at stroke onset can be a predictor of poor stroke outcome. However, beyond the acute stage, MMP-9 may play beneficial role in stroke recovery.

Impact of CYP3A5 and MDR-1 gene polymorphisms on the dose and level of tacrolimus among living-donor liver transplanted patients: single center experience

Abstract Aim of work: To assess the impact of Cytochrome P450 3A5 (CYP3A5) and multidrug resistance-1 gene (MDR-1) single nucleotide polymorphisms on the dose and blood level of tacrolimus among liver transplanted patients. Patients and methods: We enrolled a prospective study of 41 liver transplanted patients. Dose-adjusted trough blood concentration (C/D ratio) was calculated. Polymerase chain reaction-restriction fragment length polymorphism followed by sequencing was done for genotyping of CYP3A5*3 (6986A > G). Results: At 1 week, 1 and 3 months C/D ratio were significantly lower in CYP3A5 expressers *1/*1 patients compared to non-expressers *3/*3. Conclusion: CYP3A5 (6986A > G) genotype, rather than MDR-1 (2677G > A/T) variant, has an impact on tacrolimus pharmacokinetics.

Subclinical hyperthyroidism as a potential factor for dysfunctional uterine bleeding

Objective. To evaluate the functional status of the thyroid gland in apparently euthyroid women with dysfunctional uterine bleeding. Materials and methods. Forty apparently euthyroid women with menorrhagia and no pathologic lesion in the genital tract were compared with 20 women having normal menstrual cycles as controls. All women underwent hormonal evaluation: serum total and free triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH) and serum prolactin. Results. Statistically significant differences were observed in the values of TSH, total T3, free T3, free T4 and total T4 between the menorrhagia and the control group. Prolactin was increased significantly in the menorrhagia group. Conclusion. Subclinical hyperthyroidism can be a potential risk factor for dysfunctional uterine bleeding. Other studies are needed to confirm our findings.

Interferon-γ and Interleukin-10 Gene Polymorphisms are not Predictors of Chronic Hepatitis C (Genotype-4) Disease Progression.

Immunoregulatory cytokines have an influence on hepatitis C virus (HCV) infection outcome. This study aimed to determine whether single nucleotide polymorphisms (SNP) in IFN- γ and IL-10 genes are associated with susceptibility and/or are markers of prognosis regarding chronic hepatitis C outcomes. IFN γ (+874T/A) and IL-10 (-1082G/A) genotypes were determined in 75 HCV genotype 4 patients with different disease severities (chronic hepatitis, n=25, liver cirrhosis and hepatocellular carcinoma (HCC) on top of liver cirrhosis, n=50) and 25 healthy participants using allele-specific polymerase chain reaction. No statistical differences in allele or genotype distributions of IFN γ and IL-10 genes were detected between patients and controls or between patientgroups. No significant difference in the frequency of IL-10 SNP at position -1082 or IFN-γ at position +874T/A was found between chronic HCV genotype 4 and with progression of disease severity in liver cirrhosis or HCC. In conclusion; interferon-γ and interleukin-10 gene polymorphisms are not predictors of disease progression in patients with chronic hepatitis C (Genotype-4).

Triple Test Screening for Down Syndrome: An Egyptian-Tailored Study

Background The incidence of Down syndrome (DS) in Egypt varies between 1∶555 and 1∶770 and its screening by triple test is becoming increasingly popular nowadays. Results, however, seem inaccurate due to the lack of Egyptian-specific information needed for risk calculation and a clear policy for programme implementation. Our study aimed at calculation and validation of the triple marker medians used in screening Egyptian females as well as to recommend programme conventions to unify screening in this country. Methods The study was conducted on 668 Egyptian women, in weeks 15–20 of pregnancy as proven by sonar. Chorionic gonadotropin (CG), α-fetoprotein (AFP) and unconjugated oestriol (uE3) were measured on Siemens Immulite analyzer. Medians of the three parameters were calculated, regressed against gestational age (GA) and weighted by the number of participants/week. Equations were derived to adjust each parameter to the maternal weight and were centered on the median Egyptian weight. Prisca software was fed with the above data, multiples-of-median (MoM) and DS risks were calculated and the screening performance was evaluated at a mid-trimester risk cutoff of 1∶270. Results Log-linear [AFP/uE3 = 10(A+B*GA)] and exponential equations [CG = A*e (B*GA)] were derived and the regressed medians were found to follow similar patterns to other Asian and Western medians. Oestriol was always lowest (even halved) while CG and AFP were intermediate. A linear reciprocal model best fitted weight distribution among Egyptians and successfully adjusted each parameter to a weight of 78.2 kg. Epidemiological monitoring of these recommendations revealed satisfactory performance in terms of 6.7% initial positive rate and 1.00 grand MoM. Conclusions Adoption of the above recommendations is hoped to pave the way to a successful DS screening programme tailored to Egyptian peculiarities.

Association of folate intake, dietary habits, smoking and COX-2 promotor −765G > C polymorphism with K-ras mutation in patients with colorectal cancer

BACKGROUND Understanding the role of environmental and molecular influences on the nature and rate of K-ras mutations in colorectal neoplasms is crucial. COX-2 polymorphisms -765G>C may play a role in carcinogenic processes in combination with specific life-style conditions or dependent on the racial composition of a particular population. If mutational events play an important role in colorectal carcinogenesis sequence, one can hypothesize that modification of these events by life-style or other factors would be a useful prevention strategy. AIM OF WORK To explore the association between K-ras mutation and potential variables known or suspected to be related to the risk of colorectal cancer (CRC) as well as determining the possible modulating effect of the COX-2 polymorphism, -765G>C. SUBJECTS AND METHODS The study was conducted on 80 patients with colorectal cancer from Tropical Medicine and Gastrointestinal Tract endoscopy Departments and those attending clinic of the National Cancer Institute, Cairo University during the period extending from April 2009 to March 2010. Full history taking with emphasis on the risk factors of interest, namely age, sex, family history, smoking and dietary history. Serum CEA and CA19-9, RBCs folic acid and occult blood in stool were done to all samples. K-ras protooncogene mutation at codon 12 (exon 1) and cyclooxygenase 2 (COX-2) -765G>C polymorphism were determined by PCR-RFLP. RESULTS The K-ras mutation was positive in 23 (28.7%) patients. COX-2 polymorphism revealed GG in 62.5%, GC in 26.2 % and CC genotype was found in 11.3 % of cases. The mean red blood cell folic acid level was lower in the K-ras positive group (100.96±51.3 ng/ml) than the negative group (216.6±166.4 ng/ml), (P<0.01). Higher folate levels were found in males than females (median=173 ng/ml and 85 ng/ml; respectively, P=0.002) with adjusted odds ratio (OR) of 0.984. Only, the RBCs folate (P=0.0018) followed by gender (P=0.036) contributed significantly in the discrimination between patients prone to develop K-ras mutation and those who are not. CONCLUSION RBC folic acid was significantly deficient in CRC (colorectal cancer) patients with K-ras mutations in comparison with CRC patients free of the mutations, suggesting that folic acid may be a risk factor for K-ras mutation development.

Serum matrix metalloproteinase-9 in acute ischemic stroke and its relation to stroke severity

Background Thrombolytic therapy is currently the only FDA-approved treatment for acute ischemic stroke. Hence, early diagnosis and risk stratification is of great importance in management. Objective The aim of this work was to study serum level of matrix metalloproteinase-9 (MMP-9) within 24 h of acute ischemic stroke onset and its relation with clinical severity. Patients and methods Thirty patients with acute ischemic stroke were subjected to measurement of serum MMP-9 within 24 h of stroke onset and clinical assessment of stroke severity. Thirty healthy volunteers of matched age and sex were included as controls. Results Fifteen male and 15 female patients with a mean age of 61 ± 7.11 years were studied. The mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 11.17 ± 4.76. The mean serum level of MMP-9 in patients was 998.8 ± 154.72 ng/ml, which was significantly higher compared with the serum level of MMP-9 in controls ( P = 0.003). The mean NIHSS of patients with normal serum level of MMP-9 was less than the mean NIHSS in patients with high MMP-9 serum levels ( P = 0.003). There was a significant positive correlation between serum level of MMP-9 and NIHSS score ( r = 0.5; P = 0.005) even after adjustment of other variables )age, sex, diabetes, hypertension, fasting blood sugar, uric acid, serum triglycerides, serum cholesterol, and right and left carotid intima media thickness( ( r = 0.48; P = 0.032). Conclusion Serum MMP-9 level was found to be high in acute ischemic stroke patients and correlated with clinical stroke severity.