RESUMO
BACKGROUND: Ischemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. METHODS: A case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. RESULTS: Our study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01-2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). CONCLUSION: We deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.
RESUMO
Background: Mammography is a method widely used for the diagnosis of breast disorders in women and may help detect breast cancer in its early stages. Male breast cancer often remains undiagnosed or is poorly controlled until serious complications arise; therefore, the use of screening methods is needed to help with early diagnosis. Methods: From a total of 1,667 registered mammography cases screened, 17 male breast disease cases were included in this study. Mammography and ultrasound data were analyzed by Statistical Package of Social Sciences v.22 (SPSS). Diagnosis was made following biopsy in suspicious cases, and histopathological and immunological findings of all such patients were obtained for final diagnosis. Results: The mean age of the patients was 35 years (range, 14-70 years); 17.6% of the cases were aged 37 yrs, and 2 cases were aged 51 and 52 yrs. Of the 17 cases, 11 had breast lesions, and skin thickening was observed in only 1 case. The different patterns of lesions detected were asymmetry of the parenchyma, mastitis, and hamartoma (n = 1 each), malignant lesions (n = 2), and gynecomastia (n = 6). According to the BI-RADS categorization, 8 cases were benign, one case was probably benign, and 2 cases were likely malignant. In the 2 cases with malignant lesions, pathological diagnosis was made after hematoxylin and eosin and immunocytochemistry examination as invasive ductal carcinoma (IDC) of no special type (NST), grade II and grade III. Conclusions: Most breast lesions in this study population were benign, while IDC was the most common malignancy encountered. Mammography is currently the most accurate and cost-effective method for detecting breast lesions. The findings of our study may help increase awareness of male breast cancer and encourage Saudi men at risk to perform self-breast exam and undergo routine breast screening.
RESUMO
This review discusses the epidemiology, pathophysiology, genetic etiology, and management of phenylketonuria (PKU). PKU, an autosomal recessive disease, is an inborn error of phenylalanine (Phe) metabolism caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene. The prevalence of PKU varies widely among ethnicities and geographic regions, affecting approximately 1 in 24,000 individuals worldwide. Deficiency in the PAH enzyme or, in rare cases, the cofactor tetrahydrobiopterin results in high blood Phe concentrations, causing brain dysfunction. Untreated PKU, also known as PAH deficiency, results in severe and irreversible intellectual disability, epilepsy, behavioral disorders, and clinical features such as acquired microcephaly, seizures, psychological signs, and generalized hypopigmentation of skin (including hair and eyes). Severe phenotypes are classic PKU, and less severe forms of PAH deficiency are moderate PKU, mild PKU, mild hyperphenylalaninaemia (HPA), or benign HPA. Early diagnosis and intervention must start shortly after birth to prevent major cognitive and neurological effects. Dietary treatment, including natural protein restriction and Phe-free supplements, must be used to maintain blood Phe concentrations of 120-360 µmol/L throughout the life span. Additional treatments include the casein glycomacropeptide (GMP), which contains very limited aromatic amino acids and may improve immunological function, and large neutral amino acid (LNAA) supplementation to prevent plasma Phe transport into the brain. The synthetic BH4 analog, sapropterin hydrochloride (i.e., Kuvan®, BioMarin), is another potential treatment that activates residual PAH, thus decreasing Phe concentrations in the blood of PKU patients. Moreover, daily subcutaneous injection of pegylated Phe ammonia-lyase (i.e., pegvaliase; PALYNZIQ®, BioMarin) has promised gene therapy in recent clinical trials, and mRNA approaches are also being studied.
