MDR1 C3435T polymorphism in patients with breast cancer

BACKGROUND: The human multidrug-resistant gene (MDR1) encodes P-glycoprotein (Pgp), a membrane-bound efflux transporter conferring resistance to a number of natural cytotoxic drugs and potentially toxic xenobiotics. Single-nucleotide polymorphisms (SNPs) in MDR1 gene are associated with phenotypic variation in Pgp expression levels of tissue. SNPs may alter the physiological protective role of Pgp and, therefore, influence disease risk. METHODS: In our study we identified the MDR1 C3435T polymorphism in breast cancer patients (n = 57) and healthy subjects (n = 50). DNA was extracted from peripheral blood samples by standard phenol/chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism. RESULTS: We obtained CC, CT and TT genotype frequencies in breast cancer patients as 12.3%, 57.9% and 29.8%, respectively. In the control group, frequencies of genotypes were found as 36% for CC, 46% for CT and 18% for TT. We observed difference in SNPs in MDR1 gene C3435T polymorphism between breast cancer patients and healthy controls (chi(2) = 8.66, df = 2, p = 0.013). The C allele frequency was found in 41.2% and the T allele frequency was found in 58.8%. C3435T MDR1 gene allele frequencies in breast cancer patients as compared to results in control group were as follows: [OR = 1.5 (95% CI: 1.09-1.96)]. In the patient group, T allele frequency was significantly higher than controls (p <0.01). Clinicopathological parameters of patients with breast cancer were compared for C3435T polymorphism. We did not find any significant difference between clinicopathological parameters and MDR1 phenotype of breast cancer patients. The progression-free survival rate in a subgroup analysis based on MDR1 genotypes with CC genotype was 71.4%, CT genotype was 75.7%, and TT genotype was 88.2%, respectively. This difference was not statistically significant (log rank p = 0.63). CONCLUSIONS: Results of the present study demonstrated a 1.5-fold increased risk for development of breast cancer in T allele carriers.     

The relationship between frontal sinusitis and localization of the frontal sinus outflow tract: a computer-assisted anatomical and clinical study

OBJECTIVE: To evaluate the relationship between frontal sinusitis and the localization of the frontal sinus outflow tract medial or lateral to the superior attachment of the uncinate process (UP). DESIGN: A retrospective anatomical and clinical study. SETTING: An ear, nose, and throat clinic in i?li Etfal Teaching and Research Hospital, Istanbul, Turkey. PATIENTS: Paranasal sinus computed tomographic scans of 486 sides of the frontal sinuses (hereafter referred to as sides) of 243 patients who had chronic sinusitis were evaluated. In 125 sides (26%), the superior attachment of the UP could not be identified. In the remaining 361 sides (74%), the prevalence of superior attachment of UP types and the presence of frontal sinusitis in each side were recorded. Localization of the frontal sinus outflow tract was determined according to the superior attachment of the UP. Drainage of the frontal sinus to the middle meatus (medial to the superior attachment of the UP [types 1-3]) was classified as group 1, and drainage of the frontal sinus to the ethmoid infundibulum (lateral to the superior attachment of the UP [types 4-6]) was classified as group 2. RESULTS: Frontal sinusitis was found in 125 (35%) of 361 sides. The distribution of frontal sinusitis was 97 (41%) of 237 in group 1 and 28 (23%) of 124 in group 2. Group 1 drainage had a statistically significant presence of frontal sinusitis (chi(2) = 12.11; P<.001). The prevalence of superior attachment of UP types was 63% for type 1/2, 3% for type 3, 12% for type 4, 14% for type 5, and 8% for type 6. CONCLUSIONS: Frontal sinus outflow tract, which is medial to the superior attachment of the UP, is more common than the lateral one. There is a statistically significant relation between the presence of frontal sinusitis and the frontal sinus outflow tract, which is medial to the superior attachment of the UP.     

Validation of diffuse correlation spectroscopy against 15O-water PET for regional cerebral blood flow measurement in neonatal piglets

Diffuse correlation spectroscopy (DCS) can non-invasively and continuously asses regional cerebral blood flow (rCBF) at the cot-side by measuring a blood flow index (BFI) in non-traditional units of cm²/s. We have validated DCS against positron emission tomography using ¹⁵O-labeled water (¹⁵O-water PET) in a piglet model allowing us to derive a conversion formula for BFI to rCBF in conventional units (ml/100g/min). Neonatal piglets were continuously monitored by the BabyLux device integrating DCS and time resolved near infrared spectroscopy (TRS) while acquiring ¹⁵O-water PET scans at baseline, after injection of acetazolamide and during induced hypoxic episodes. BFI by DCS was highly correlated with rCBF (R = 0.94, p < 0.001) by PET. A scaling factor of 0.89 (limits of agreement for individual measurement: 0.56, 1.39)×10⁹× (ml/100g/min)/(cm²/s) was used to derive baseline rCBF from baseline BFI measurements of another group of piglets and of healthy newborn infants showing an agreement with expected values. These results pave the way towards non-invasive, cot-side absolute CBF measurements by DCS on neonates.     

Serum lipid and leptin concentrations in hypopituitary patients with growth hormone deficiency

OBJECTIVE: To investigate the effects of growth hormone (GH) deficiency on serum lipid and leptin concentrations in hypopituitary patients taking conventional replacement therapy and to determine the relations between leptin and gender and anthropometric and metabolic variables. SUBJECTS: Twenty-one GH deficient adult hypopituitary patients (15 women, six men) and 21 (14 women, seven men) age, sex and body mass index (BMI) matched healthy controls. MEASUREMENTS: After an overnight fast, anthropometric parameters were measured and body composition was determined by a bioelectrical impedance analyser. Venous blood samples were obtained for the measurements of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, intact insulin, insulin-like growth factor 1 (IGF-1) and leptin concentrations. Serum leptin and hormones were analysed by radioimmunoassay. RESULTS: Hypopituitary patients with GH deficiency showed significantly higher triglyceride, total and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The unfavourable lipid profile was particularly evident in women. Significantly higher leptin concentrations were found in patients compared with healthy controls with similar body fat content (23. 5+/-11.8 ng/ml vs 11.7+/-6.9 ng/ml, P=0.01). This difference remained significant even when leptin values were expressed in relation to fat mass percentage (0.79+/-0.40 vs. 0.42+/-0.17 ng/ml%, P<0.05) and fat mass kg (1.32+/-0.81 vs 0.66+/-0.30 ng/ml kg, P<0. 05). Significant positive correlations were observed between leptin concentrations and body fat percentage and age in the control group. In patients the sole significant relation between leptin and study parameters was the positive correlation observed between leptin and total cholesterol concentrations. Serum leptin concentrations were significantly higher in women than men in the control group, but not in the patients. No significant gender difference was observed when leptin concentrations were expressed in relation to fat mass (percentage and kg). CONCLUSION: Growth hormone deficient hypopituitary patients (particularly women) on conventional replacement therapy have a more atherogenic lipid profile. Leptin concentrations are increased in GH deficient adults even after adjustment for percentage body fat and body fat mass (kg). Although the nature of our data does not allow us to draw any conclusions on the mechanism(s) of increased leptin concentrations in GH deficiency, decreased central sensitivity to leptin and increased leptin production from per unit fat mass, or alterations in leptin clearance, might be operative.     

Brachial plexus injury during open heart surgery--controlled prospective study

BACKGROUND: Postoperative brachial plexus injury is often reported because the brachial plexus is stretched by sternotomy and the use of sternal retractors during open heart surgery. In many studies, brachial plexus injuries have been demonstrated by postoperative electrophysiological studies in susceptible patients. In this study, we estimated the incidence, severity, and type of brachial plexus injuries by routine preoperative and postoperative electrophysiological studies of patients undergoing open heart surgery. METHODS: Patients undergoing coronary artery bypass grafting (CABG) surgery (Group 1), heart valve surgery (Group 2), or peripheral vascular surgery (Group 3) were included in the investigation. Electrophysiological studies of both upper extremities were performed five days before and three weeks after the operation. RESULTS: Peripheral nerve problems were found preoperatively in 23 of the 112 patients (21 %). These problems persisted, but similar findings were obtained postoperatively from the left upper extremities of six of the 42 CABG (14 %) and two of the 24 heart valve (8 %) patients who had had normal preoperative evaluations. The patients with injured nerves were older and had undergone longer operation times. There were no differences between the patients with injured nerves and the others with respect to mammary artery harvesting or other operative variables. CONCLUSIONS: There are no reports in the literature of routine preoperative and postoperative electrophysiological studies in large patient groups to evaluate brachial plexus injury during open heart surgery. It is known that heart surgery sometimes causes partial brachial plexus injury, especially in the lower trunk. However, these peripheral nerve problems are usually not considered clinically important and are not investigated. Patients undergoing open heart surgery must be closely followed up for peripheral nerve injury during the postoperative period.