Congenital hypothyroidism: a five-year retrospective study at Children's University Hospital, Damascus, Syria.

Background: Congenital hypothyroidism (CH) is a treatable thyroid hormone deficiency that causes severe mental retardation and growth deficiency if not detected and treated early. The treatment of CH is simple, inexpensive, and effective. With early detection and treatment, infants usually develop normally without mental retardation and become productive members of society. In Syria, a screening program is not available, and there is no published information about the actual incidence of CH. However, an unpublished pilot study supported by the International Atomic Energy Agency showed that the incidence of CH in Syria is more than the global incidence, indicating the importance of the application of a CH screening program in Syria. Objectives: The present study aimed to collect baseline information about CH in Syria to estimate the potential need of a screening program. Materials and methods: This retrospective study was performed at Children's University Hospital, Damascus. The study included the medical records of patients who had CH as the final diagnosis between 2008 and 2012. Some patients were diagnosed elsewhere and were then admitted to the hospital within the same period. Results: In this study, 70 cases registered as CH, 67 of them had confirmed, 40 (57.1 %) were male and 30 (42.9%) were female. Among the patients, (51.4%, n = 36) involved parental consanguinity and 6 had a family history of hypothyroidism. Additionally, 74.3% were not diagnosed during the first month of life. The signs and symptoms most commonly detected were cretinoid face (60%), pallor (44.3%), delayed neuropsychomotor development (37.1%), growth failure (36.7%), jaundice (35.7%), and hypotonia (35.7%). Conclusion: A CH screening program is necessary in Syria owing to the low specificity of the signs and symptoms of CH, which can lead to delayed diagnosis, and the presence of asymptomatic cases (subclinical hypothyroidism).

The role of serum surfactant protein D as a biomarker of exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The exacerbation of chronic obstructive pulmonary disease (COPD) is a major factor for the high mortality associated with the disease. There is a paucity in the lung-specific biomarkers which diagnose these exacerbations. Surfactant protein D (SP-D) is a promising biomarker in predicting clinical outcomes for patients with COPD, is lung-specific and can be detected in serum. However, the profile in which serum concentrations of SP-D change during acute exacerbation is still unclear. This study aims to estimate and compare the concentrations of serum SP-D in patients with stable disease and during the exacerbation. METHODS: A cross-sectional study was conducted which composed of apparently healthy individuals (n = 28), which included 14 smokers and 14 nonsmokers, patients with stable COPD (n = 28), and patients experiencing acute exacerbations (n = 28). Pulmonary functions were performed for all groups. Serum SP-D concentrations were measured using enzyme-linked immunosorbent assay (ELISA). These concentrations were compared by analysis of variance. RESULTS: Serum SP-D levels were significantly elevated in patients with acute exacerbations (508.733 ± 102.813 ng/ml) compared to patients with stable COPD (337.916 ± 86.265 ng/ml) and healthy subjects (177.313 ± 46.998 ng/ml; p <  0.001). Serum SP-D levels correlated inversely with lung function parameters including FEV1%pred, FVC%pred and FEV1/FVC. CONCLUSION: Serum SP-D levels are raised early on during acute exacerbations of COPD, which could be a potential early diagnostic biomarker for COPD exacerbations.

Diagnosis and clinical features of organic acidemias: A hospital-based study in a single center in Damascus, Syria.

BACKGROUND: Organic acidemias (OA) are a group of heterogeneous metabolic inherited disorders characterized by the accumulation of organic acids in body fluids and tissues. These are rare disorders and infrequently reported worldwide. In Syria, there is a lack of information regarding these disorders. OBJECTIVE: Our hospital-based study aimed to describe the pattern of clinical and demographic presenting features of organic acidemias among Syrian children and to shed light on the diagnostic experience of organic acidemias in the Children's Hospital of Damascus through a five year period. MATERIAL AND METHODS: We conducted a retrospective cohort study by reviewing the medical records of OA patients in the Children's Hospital of Damascus between 2008 and 2012. All cases were investigated by metabolic work up, including the acylcarnitine profile performed by tandem mass spectrometry (MS/MS) and quantitative urine organic acid analysis performed by gas chromatography mass spectrometry (GC-MS). RESULTS: A total of 70 OA confirmed cases were included in the study. There were 46 males and 31 females. Twenty-seven cases were diagnosed after the first year of life. Methylmalonic acidemia was the most frequent disorder (57.1%). There were relatively high rates of family history of unexplained death and OA confirmed cases (50%), consanguinity (74.2%) and mortality (21.4%). The most frequent symptoms were apnea or respiratory distress (65.7%) and vomiting (40%). CONCLUSION: The lack of specific confirmatory diagnostic tests being performed and the high mortality and consanguinity rates among OA patients suggests high incidence of OA in Syria. Further studies are needed to determine the actual incidence of OA and the cost-effectiveness of applying a governmental mandatory newborn screening program.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: A five-year retrospective study in the Children's Hospital of Damascus, Syria.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders. 21-hydroxylase deficiency is responsible for the majority of cases (90-95%) and considered the most common cause of genital ambiguity. There are no statistics concerning the prevalence of this disorder in Syria, although the high rate of consanguineous marriages indicates a possible high prevalence. OBJECTIVES: This study aims to collect baseline information about CAH in Syria to evaluate the potential need of a screening program. SUBJECTS AND METHODS: All medical records of inpatients who had CAH as a final or presumptive diagnosis at the Children's Hospital of Damascus between 2008-2012, or were diagnosed elsewhere and then admitted at the hospital for the first time within the same period, were retrospectively reviewed and divided into two groups: confirmed and suspected cases. RESULTS: Eighty-nine cases were confirmed, 25 were still suspected. Of the 89 confirmed cases: 20 (22.5%) were males, 66 (74.1%) were females, and 3 were ambiguous. Sixty-one patients (68.5%) were of the salt wasting type and 28 (31.5%) were of the simple virilizing type. The mortality rate was 6.7%. Thirty-two females were assigned as males at birth. Seventeen cases (19.1%) underwent previous hospitalization. 69.7% of patients were not diagnosed during the first month of life. Of the 25 suspected cases: 12 were males, 8 were females and 5 were ambiguous. Confirmatory tests had not been performed because of death in 7 patients (28%) and early discharge upon parental request in another 7 patients (28%). CONCLUSION: A mandatory screening program for CAH in Syria seems necessary due to the obvious lack of awareness, delayed diagnosis and high expected prevalence. However, further efforts are needed to confirm the effectiveness of such a program in the Syrian society.

Emerging Role of Non-collagenous Bone Proteins as Osteokines in Extraosseous Tissues.

Bone is a unique tissue, composed of various types of cells embedded in a calcified extracellular matrix (ECM), whose dynamic structure consists of organic and inorganic compounds produced by bone cells. The main inorganic component is represented by hydroxyapatite, whilst the organic ECM is primarily made up of type I collagen and non-collagenous proteins. These proteins play an important role in bone homeostasis, calcium regulation, and maintenance of the hematopoietic niche. Recent advances in bone biology have highlighted the importance of specific bone proteins, named "osteokines", possessing endocrine functions and exerting effects on nonosseous tissues. Accordingly, osteokines have been found to act as growth factors, cell receptors, and adhesion molecules, thus modifying the view of bone from a static tissue fulfilling mobility to an endocrine organ itself. Since bone is involved in a paracrine and endocrine cross-talk with other tissues, a better understanding of bone secretome and the systemic roles of osteokines is expected to provide benefits in multiple topics: such as identification of novel biomarkers and the development of new therapeutic strategies. The present review discusses in detail the known osseous and extraosseous effects of these proteins and the possible respective clinical and therapeutic significance.

Syrian females with congenital adrenal hyperplasia: a case series.

BACKGROUND: One of the most common types of congenital adrenal hyperplasia is an autosomal recessive disorder with 21-hydroxylase deficiency. The classical form, defined by cortisol insufficiency, is accompanied by prenatal androgen excess causing variable masculinization degrees of external genitalia in babies with a 46, XX karyotype. CASES PRESENTATION: These five case reports highlight the management of Syrian females aged between 0 and 32 years with congenital adrenal hyperplasia. Two of the patients have been raised as males, while two had reconstructive surgery and one had hormonal therapy. Becoming mother was achieved by two patients CONCLUSION: The integrated treatment of females with classical congenital adrenal hyperplasia CAH, which includes appropriate surgical procedures and controlled hormonal therapy, gives these females the opportunity to live as they are, and perhaps as mothers in the future.

NT-proBNP in monitoring treatment of patients with congestive heart failure.

OBJECTIVE: The aim of this study was to assess the utility of plasma N-terminal proBrain Natriuretic Peptide (NT-proBNP) assay in monitoring the therapy of congestive heart failure patients. BACKGROUND: Treatment of congestive heart failure aims to improve left ventricular function by reducing the pressure and volume overload. The human heart secretes brain natriuretic peptide in response to increased intracardiac volume or pressure. Therefore the therapy of congestive heart failure could have an effect on the plasma natriuretic peptide level. METHODS: The study included 149 patients with heart failure admitted to the Al-Assad and Al-Mowasah Hospitals, Damascus, Syria, during a 19-month period from February 2004 to September 2005. The age of the patients was between 35-85 years (mean+/-SD: 57+/-13.5). The patients were clinically divided into 4 groups according to the New York Heart Association Classification. Plasma NT-proBNP levels were measured and echocardiography was performed in all patients. We repeated physical examination, echocardiography, the patient's history, and the NT-proBNP assay in 46 patients from different stages after 3 months of drug treatment. The monitored patients were divided into three subgroups according to the clinical state: (A) 21 patients who clinically improved; (B) 18 patients with no clinical improvement; (C) 7 patients who were clinically stable. Plasma NT-proBNP levels were measured by electrochemiluminescence immunoassay (Roche). Statistical analysis was carried out by T-distribution, and the difference was considered to be significant at P < 0.05. RESULTS: The plasma NT-proBNP levels significantly decreased (P < 0.001) in clinically improved patients after 3 months of treatment, and this was accompanied by improvement of the echocardiographic data and symptoms. In contrast, the plasma NT-proBNP levels increased in patients with no clinical improvement and a decrease in the ejection fraction after 3 months of therapy, but the difference was not statistically significant (P > 0.05). There was also no statistically significant difference (P>0.05) between the plasma NT-proBNP level at diagnosis and after 3 months of treatment in clinically stable patients. CONCLUSION: The plasma NT-proBNP levels alter in response to drug therapy and can be used in monitoring treated patients with congestive heart failure.

N-terminal-probrain natriuretic peptide and echocardiography in patients with systolic heart failure.

OBJECTIVE: To compare plasma N-terminal-probrain natriuretic peptide (NT-proBNP) levels with echocardiographic data in patients with systolic heart failure. METHODS: The study included 101 patients with systolic heart failure admitted to Al-Assad and Al-Moussa Hospitals, Damascus, Syria over a 10-month period from February 2004 to January 2005. The findings of the physical examination, electrocardiogram and blood pressure measurement were recorded along with the patient's history, risk factors, and drug treatment. We divided the patients into 4 groups according to the New York Heart Association classifications; class I=19, class II=22, class III=28, class IV=32 patients. We compared the values with 21 age-matched controls with no heart diseases (age range 49-80 years). During the study period, we carried out the plasma NT-proBNP levels and echocardiography of all patients and controls group. We used electroche-miluminescence immunoassay in measuring plasma NT-proBNP. Authorized physicians evaluated the ejection fraction (EF), systolic pulmonary pressure, and left ventricular end systolic diameter. Statistical analysis used was T-Distribution, and the difference considered to be significant at p<0.05. RESULTS: The plasma NT-proBNP levels in patients of asymptomatic heart failure class I (mean 1,038 pg/ml) were significantly higher (p<0.001) as compared with the controls (40.9 pg/ml), and it increased directly with the severity of heart failure. Plasma NT-proBNP levels were conversely correlated with the ejection fraction EF (r= -0.56, p<0.001) and it increased as the EF declined. There was a significant direct linear correlation between plasma NT-proBNP levels and the left ventricular end systolic diameter (r=0.57) and systolic pulmonary pressure r=0.54. CONCLUSION: The left ventricle releases the B-type natriuretic peptide in response to volume or pressure overload, its high level reflects the poor cardiac systolic function, which corresponds with the echocardiographic data.

Human Kallikrein-2, Prostate Specific Antigen and Free- Prostate Specific Antigen in Combination to Discriminate Prostate Cancer from Benign Diseases in Syrian Patients.

BACKGROUND: The high incidence of prostate cancer as the most common malignancy in males in many countries raises the question of developing reliable detection tests. The prostate specific antigen (PSA) test is the most widely used for screening for prostate cancer; however, its low specificity elevates the number of unnecessarily biopsies. Serum human kallikrein-2 (hK2) is considered as a promising marker, and especially its ratio to fPSA, for predicting the presence of malignancy to select the best choice referring to biopsy or surveillance. In this study, we investigated the role of hK2 and its combinations with other markers to discriminate prostate cancer from benign diseases in Syrian patients. MATERIALS AND METHODS: In this prospective oriented cross-sectional cohort study, serum samples were collected from patients referred to many Hospitals in Damascus, Syria, between May 2011 and March 2012, and diagnosed with biopsy proven benign prostate hyperplasia (BPH) or prostate cancer (PCa). Serum was analyzed for hK2, PSA and fPSA, and the ratios of fPSA/PSA and hK2/fPSA were calculated. RESULTS: We found that mean hK2/fPSA ratios were significantly higher (P=0.01) in prostate cancer patients than in the BPH or control groups. Also the ratio hk2/fPSA gave the largest area under the curve (AUC:0.96) which was significantly larger than for fPSA/PSA (AUC:0.41) indicative of higher specificity. CONCLUSIONS: Our results demonstrate that the ratio of hK2/fPSA might be superior to the use of fPSA/PSA alone. The hK2 could be shown to enhance the early detection of prostate cancer; especially the ratio hK2/fPSA improves specificity and hence may reduce the number of negative biopsies.

Frequency of Unnecessarily Biopsies among Patients with Suspicion of Prostate Cancer in Syrian Men.

BACKGROUND: The prevalence of prostate cancer is considered high in many countries, and screening tests are very important in order to detect prostate cancer in its early stages; however false positivity with these screening tests means that a lot of patients undergo unnecessary biopsy, which is an invasive procedure, for the confirmatory test. The purpose of this study was to estimate the frequency of unnecessary biopsy cases in patients referred for prostate biopsy in one of the most important and overload cancer centers in Syria. MATERIALS AND METHODS: Retrospective data for a period of four years between January 2009 and December 2012 were collected in Al- Bayrouni University Medical hospital in Damascus, Syria. The patients from whom data were collected were referred to our histopathological department because of elevated prostate specific antigen (PSA) serum or an abnormal digital rectal examination (DRE). All patients underwent prostatic TRUS-guided biopsies. Diagnosis of prostate cancer (PCa) or benign prostatic hyperplasia (BPH) was based on histopathological examination and prostate cancers cases were graded and scored according to the Gleason score system. RESULTS: For the 406 patients referred to biopsy, the mean±SD age was 58.4 ±23.3 years. The mean ± SD PSA level was 49.2±21.5 ng/ ml. Of the total we found 237 patients diagnosed with PCa (58. 4%), 166 patients with BPH (40.9%) and 3 cases were unable to be diagnosed (0.7%) because of biopsy collection errors. CONCLUSIONS: Our study shows that a high percentage of patients are undergoing unnecessary biopsy, which suggests that the performed screening tests had a high level of false positive and may need re-evaluation.

Cardiovascular risk among university students from developed and developing nations.

BACKGROUND: A key aspect in halting global increase in cardiovascular events is prevention and especially prevention at an early age. Unfortunately, global data regarding cardiovascular risk factors in the young are limited. Therefore the objectives of this study were to identify the most common cardiovascular risk factors among young adults in a university setting in both developed and developing countries. METHODS: Lifestyle and cardiovascular risk factors (smoking status, rates of physical activity, alcohol use, family history, blood pressure, fasting lipid panel, fasting blood glucose) were prospectively evaluated in young adults at three different university settings [University of Michigan (Ann Arbor, USA), University of Kalamoon (Deratiah, Syria), and Kakatiya University (Warangal, India)]. RESULTS: A total of 296 subjects (mean age and standard deviation 22 ± 3 years) were evaluated. Rates of current smoking were markedly higher (p < 0.001) in Syria (43%) compared with the USA (6.2%) and India (1.7%). Subjects in India were significantly (p < 0.001) less likely to engage in physical activity (20.2%) compared with the USA (90.7%) and Syria (68.8%). Fasting blood glucose levels and body mass index were significantly higher (p < 0.001) in Syria as compared to other countries. Significant differences were also noted in LDL, HDL, and triglycerides among the three sites. CONCLUSIONS: Cardiovascular risk factors among young adults in a university setting vary depending on global setting. Based upon the results of this study, targeted interventional programs based on risk findings from individual countries may be a reasonable future strategy to help reduce long term cardiovascular morbidity and mortality.

Effect of hormone replacement therapy on hemostatic variables in post-menopausal women.

OBJECTIVE: Hormone replacement therapy (HRT) has been increasingly promoted over the last 40 years to improve quality of life, and to reduce the risks of osteoporotic fractures and coronary heart disease (CHD). Recent randomized controlled clinical trials reported that HRT usage is associated with an increased risk of myocardial infarction (MI), stroke, and venous thrombosis. We conducted this study to evaluate the mean levels of some hemostatic parameters among groups that differ in estrogen levels and age. METHODS: We studied 150 healthy women in an observational comparative study, divided into 3 groups. Forty women were post-menopausal using HRT for a period of 6 months to 17 years. Fifty-five women were post-menopausal and were not using HRT. Fifty-five women were younger pre-menopausal women with an age range of 20-54 years. The HRT group women were recruited from gynecologist private clinics while the other 2 groups were recruited in a random way from the society in Damascus, Syria between August 2002 and January 2003. We determined estradiol, fibrinogen, antithrombin III (AT III) and protein C in all women. RESULTS: When compared with post-menopausal non-users group, current HRT users had higher mean levels of estradiol, but lower mean levels of AT III and protein C, and similar mean levels of fibrinogen. When compared with pre-menopausal group, current users had similar mean levels of estradiol, AT III and protein C, but higher mean levels of fibrinogen. However, post-menopausal non-users women had higher mean levels of fibrinogen and lower mean levels of AT III and protein C when compared with pre-menopausal women. CONCLUSION: Hormone replacement therapy treatment did not change fibrinogen mean levels, but it caused a decrease in AT III and protein C mean levels.