Novel Associations between BRCA1 Variants C.181 T>G (Rs28897672) and Ovarian Crisk in Saudi Females.

BACKGROUND: Mutations in BRCA1 gene have been implicated in ovarian cancers, and BRCA testing may be conducted in high-risk women. This study was designed to determine the frequency of three single nucleotide polymorphisms (SNPs) variants in BRCA1 gene and BRCA1 expression in Saudi females with ovarian cancer. METHODS: Expression levels of mRNA of BRCA1 gene were studied in 10 ovarian cancer and 10 normal ovarian tissues, by quantitative real time polymerase chain reaction (qPCR). The study also included 28 females who had suffered from ovarian cancer and had been successfully operated upon and 90 healthy females with no history of cancer. Blood was drawn in EDTA tubes and used for extraction of DNA. The genotyping was carried out using Taqman® SNP Genotyping kit by RT-PCR. The variants investigated included c.871 T>C (rs799917), c.1040 G>A (rs4986852), c.181 T>G (rs28897672) in BRCA1 gene. RESULTS: The c.181 T>G (rs28897672) showed significantly different genotype and allele frequencies between the patients and the control subjects (p value = 0.002 and 0.02, respectively). The genotype TG was significantly protective (OR = 0.36, p value = 0.024). The mRNA expression of BRCA1 gene was found to be low in the ovarian cancer tissues. CONCLUSIONS: This study showed that c.181 T>G in BRCA1 genes is associated with the development of ovarian cancer in Saudis. More studies are needed to unveil other SNPs that may be associated with ovarian cancer and to understand the mechanism(s) involved in reducing the expression of BRCA1 gene in ovarian cancer tissues.

Thromboprophylaxis and mortality among patients who developed venous thromboembolism in seven major hospitals in Saudi Arabia.

INTRODUCTION: Venous thromboembolism (VTE) during hospitalization is a serious and potentially fatal condition. Despite its effectiveness, evidence-based thromboprophylaxis is still underutilized in many countries including Saudi Arabia. OBJECTIVE OF THE STUDY: Our objectives were to determine how often hospital-acquired VTE patients received appropriate thromboprophylaxis, VTE-associated mortality, and the percentage of patients given anticoagulant therapy and adherence to it after discharged. METHODS: This study was conducted in seven major hospitals in Saudi Arabia. From July 1, 2009, till June 30, 2010, all recorded deep vein thrombosis (DVT) and pulmonary embolism (PE) cases were noted. Only patients with confirmed VTE diagnosis were included in the analysis. RESULTS: A total of 1241 confirmed VTE cases occurred during the 12-month period. Most (58.3%) of them were DVT only, 21.7% were PE, and 20% were both DVT and PE. 21.4% and 78.6% of confirmed VTE occurred in surgical and medical patients, respectively. Only 40.9% of VTE cases received appropriate prophylaxis (63.2% for surgical patients and 34.8% for medical patients; P < 0.001). The mortality rate was 14.3% which represented 1.6% of total hospital deaths. Mortality was 13.5% for surgical patients and 14.5% for medical patients (P > 0.05). Appropriate thromboprophylaxis was associated with 4.11% absolute risk reduction in mortality (95% confidence interval: 0.24%-7.97%). Most (89.4%) of the survived patients received anticoagulation therapy at discharge and 71.7% of them were adherent to it on follow-up. CONCLUSION: Thromboprophylaxis was underutilized in major Saudi hospitals denoting a gap between guideline and practice. This gap was more marked in medical than surgical patients. Hospital-acquired VTE was associated with significant mortality. Efforts to improve thromboprophylaxis utilization are warranted.

Factors associated with complications in gynecological surgeries.

OBJECTIVE: To evaluate the factors associated with complications in major gynecological surgeries. METHODS: A retrospective study on major gynecological surgeries performed at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, from the year 1997-2001. A total of 555 cases were included. Risk factors associated with complications were evaluated by a unique regression analysis. RESULTS: High blood loss was associated with salpingectomy/salpingotomy, myomectomy, and total abdominal hysterectomy (TAH). Old age was associated with TAH, oophorectomy and vaginal hysterectomy. Prolonged hospitalization was associated with TAH and oophorectomy. Urinary tract infection, wound infection, nausea and vomiting were not significant postoperative complications in major gynecological surgeries. CONCLUSION: The recognition of the specific complications associated with each type of surgery are important for counseling the patients and preoperative preparation to reduce the risk of long term morbidity.

Leptin concentration during different trimesters of pregnancy and its relation to other pregnancy hormones.

OBJECTIVE: To determine the levels of leptin and other pregnancy hormones (progesterone, estradiol, folliculi stimulating hormone, luteinizing hormone and beta human chorionic gonadotropin) in pregnant females during different stages of pregnancy and to correlate these levels to maternal weight, body mass index (BMI), babies weight and babies BMI. METHODS: Leptin level and other pregnancy hormones were measured in 36 pregnant females and 30 non-pregnant females followed at King Khaled University Hospital, Riyadh, Kingdom of Saudi Arabia in the year 2001 in a prospective study. Blood samples were collected at the first, 2nd and 3rd trimester and after delivery. Correlation analysis between leptin level and pregnancy hormones, in addition to maternal weight, BMI, babies weight and BMI. RESULTS: The mean leptin levels during pregnancy and postnatally were significantly higher in pregnant females compared to the non-pregnant controls. Serum concentration of leptin increased significantly (p=0.01) in the pregnant females from 21.24 +/- 9 ng/ml during the first trimester to 26.3 +/- 8.69 ng/ml during the 2nd trimester, but insignificantly decreased to 23.29 +/- 8.62 ng/ml during the 3rd trimester (p=0.073). After delivery leptin concentration significantly decreased to 17.36 +/- 7.95 ng/ml (p=0.0025). The changes in levels of leptin during pregnancy were independent to other pregnancy hormones which showed a different pattern of variation. CONCLUSION: The changes in levels of leptin during pregnancy were independent to other pregnancy hormones which showed a different pattern of variation.

Age at menarche and the reproductive performance of Saudi women.

BACKGROUND: Saudi Arabia has undergone substantial development in the recent past with concomitant changes in living conditions, and economic and general health status that have affected the age at menarche in Saudi women. We evaluated the current age at menarche and reproductive events among Saudi women. SUBJECTS AND METHODS: Age, age at menarche, age at marriage, age of first pregnancy, number of children, and number of abortions were collected for Saudi women attending King Khalid University Hospital (KKUH) over a 3-month period in 2002. RESULTS: For 989 Saudi women, the mean age at menarche was 13.05 years. There was a decrease in the age of menarche over the past 20 years, an increase in the age of marriage, age of first pregnancy, and a decrease in the number of children and abortions. Compared with data from two decades, the age at menarche decreased significantly from 13.22 to 13.05 years. CONCLUSION: The decrease in the age of menarche among Saudi women indicates better socioeconomic status and improvements in health.

Methotrexate embryopathy in a surviving intrauterine fetus after presumed diagnosis of ectopic pregnancy: case report.

CASE: A 30-year-old woman with a history of 6 spontaneous first trimester abortions and no living children, who had previously been treated for polycystic ovarian syndrome, was given methotrexate parenterally for a suspected ectopic pregnancy at 5 weeks of amenorrhea. Later, a surviving intrauterine pregnancy was noted, and the pregnancy continued. Her baby was delivered with multiple skeletal anomalies and ambiguous genitalia. CONCLUSION: Physicians must discuss the teratogenicity of methotrexate with their patients before its administration. Careful clinical and ultrasound evaluations are recommended before the administration of methotrexate to avoid complications in pregnancy and adverse birth outcomes.

Prevalence of osteoporosis among postmenopausal females with diabetes mellitus.

OBJECTIVE: To assess the prevalence of osteopenia and osteoporosis among Saudi postmenopausal women with non-insulin dependent type 2 diabetes mellitus (T2DM). METHODS: The study was carried out at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from February 2000 to September 2002. Bone mineral density (BMD) of the lumbar spine and femoral neck using dual x-ray absorptiometry (DXA; Lunar Wisconsin), were performed in 104 postmenopausal Saudi women with T2DM, and 101 postmenopausal non-diabetic women (control). Bone mineral density was measured in gm/cm2 and both T-score and Z-score were measured but only T-score was used for analysis based on World Health Organization criteria. Bone profile, 25(OH) Vitamin D, 1,25(OH)2 Vitamin D, parathyroid hormone and urine deoxypyridinoline (DPD) were measured in most patients and controls. Body fat measurement around the biceps muscles using Futrex (body composition analyzer) were performed in patients and controls. Years postmenopausal, duration of diabetes mellitus, parity, exercise, sun exposure and milk consumption were also recorded. RESULTS: In the diabetic group, the mean spine BMD was 0.928 gm/cm2 (T-score = -2.28 SD) and for femoral neck the mean BMD was 0.817 gm/cm2 (T-score = -1.21 SD). In control group, the mean spine BMD was 1.036 gm/cm2 (T-score = -1.2) and mean femoral neck BMD was 0.914 gm/cm2 (T-score = -0.608). In the diabetic group, there was 16 (16.64%) patients with normal BMD of the spine, 42 patients (43.68%) with osteopenia (mean T-score = -1.8 SD) and 45 (46.8%) with osteoporosis (mean T-score = -3.3 SD). CONCLUSION: Osteoporosis is more common among Type 2 postmenopausal females in this ethnic group. Since both groups are postmenopausal, having equal percentage of Vitamin D deficiency, multi-parity, non exposure to sun, lack of exercise and negligible milk intake, one can conclude that the low BMD can be attributed to DM in the absence of other causes of osteoporosis.

Herpes gestationis.

Herpes gestationis, also known as Pemphigoid gestationis, is a rare autoimmune disease of pregnancy. It is characterized by itching and skin lesions. The disease causes prominently maternal discomfort but fetal and neonatal complications have been reported. There are only scattered reports of cutaneous neonatal herpes gestationis in the literature; however, the frequency and severity of fetal illness are still debated. We describe 2 cases of herpes gestationis diagnosed and managed at the King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia.

Leptin level in pregnant mothers at term and cord blood and the effect of newborns gender.

OBJECTIVE: To evaluate the leptin level in healthy pregnant mothers at term and in their newborns and its relationship to their body mass index (BMI) and gender of the newborn. METHODS: The leptin level was measured in serum of 187 pregnant women at term delivering at the King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia in July 2001 and their newborns. Correlation studies were made between leptin level and their growth parameters, and gender of the newborns. RESULTS: Leptin level of the mothers was significantly higher compared to their newborns. There was a significant correlation between leptin level in the pregnant women and their weight, BMI, and the newborns leptin level and weight, but not their height or BMI. A statistically significant difference was found between male and female newborns plasma leptin level. A significant correlation was found between male newborns leptin level and all their growth parameters, while in the female newborns there was no correlation between their leptin level and BMI. CONCLUSION: Leptin plays an important role in providing a growth promoting signal during pregnancy, but the fat mass does not seem to be the most important predictor of cord leptin level.

The inter-relationship hematological parameters between Saudi newborns and parents.

OBJECTIVE: To determine the relationship of the hematological parameters between Saudi newborns and their parents. METHODS: This study was carried out at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, over a one-year period. Venous blood samples were taken from 82 healthy Saudi pregnant women in labor at full term, their husbands, and umbilical cord blood after delivery. Estimation of the hematological indices, in addition to transferrin level were performed. RESULTS: A statistically significant correlation was found between parents and cord blood with regards to red blood count, mean corpuscular volume, mean corpuscular hemoglobulin, mean corpuscular hemoglobulin concentration and packed cell volume, while no correlation was found with hemoglobulin and transferrin. CONCLUSION: Some of the hematological indices could be mainly genetically determined including red blood count, mean corpuscular volume, mean corpuscular hemoglobulin concentration, and packed cell volume as significant correlation was found between parents and their newborns while hemoglobulin and transferrin levels were not as these variables are mainly affected by environmental factors.