The effect of topical xylometazoline on Eustachian tube function.

BACKGROUND: Topical nasal decongestants are frequently used as part of the medical management of symptoms related to Eustachian tube dysfunction. OBJECTIVE: This study aimed to assess the effect of topical xylometazoline hydrochloride sprayed in the anterior part of the nose on Eustachian tube active and passive opening in healthy ears. METHODS: Active and passive Eustachian tube function was assessed in healthy subjects before and after intranasal administration of xylometazoline spray, using tympanometry, video otoscopy, sonotubometry, tubo-tympano-aerodynamic-graphy and tubomanometry. RESULTS: Resting middle-ear pressures were not significantly different following decongestant application. Eustachian tube opening rate was not significantly different following the intervention, as measured by all function tests used. Sonotubometry data showed a significant increase in the duration of Eustachian tube opening following decongestant application. CONCLUSION: There remains little or no evidence that topical nasal decongestants improve Eustachian tube function. Sonotubometry findings do suggest that further investigation with an obstructive Eustachian tube dysfunction patient cohort is warranted.

A novel gene THSD7A is associated with obesity.

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P⩽3.75 × 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P=2.88 × 10(-5), 8.922 × 10(-6) and 2.504 × 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

Altersolanol A: a selective cytotoxic anthraquinone from a Phomopsis sp.

UNLABELLED: The cytotoxic compound Altersolanol A, an anthraquinone derivative was isolated from PM0409092 a fungus of Nyctanthes arbor-tristis (family Oleaceae). It was identified as a Phomopsis sp. by DNA amplification and sequencing of the ITS region. The chemical structure of Altersolanol A was elucidated from its physicochemical properties, 2D NMR spectroscopy and other spectroscopic data. The compound has in vitro cytotoxic activity against 34 human cancer cell lines with mean IC50 (IC70) values of 0.005 µg ml(-1) (0.024 µg ml(-1)) respectively. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage by Caspase-3 and -9 and by decreased anti-apoptotic protein expression. There are several previous reports of the anticancer activity of Altersolanol A, but we report here an extensive study using 36 cell lines which gives wider spectrum of results. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms the cytotoxic potential of Altersolanol A isolated from the endophyte Phomopsis sp. (PM0409092) of the plant Nyctanthes arbor-tristis. The compound exhibits in vitro cytotoxicity against 34 human cancer cell lines with mean IC50 (IC70) value of 0.005 µg ml(-1) (0.024 µg ml(-1)). This is an in-depth report of Altersolanol A against a panel of 34 human cancer cell lines and extends observations from previous studies indicating that Altersolanol A can be used for the development of chemotherapeutics. Altersolanol A, a kinase inhibitor, induces cell death by apoptosis through the cleavage of Caspase-3 and -9 and by decreased anti-apoptotic protein expression.

Sonography in acute ureteric colic: an experience in Dhulikhel Hospital.

BACKGROUND: Computed tomography is considered as an imaging modality of choice in acute ureteric colic. However due to concerns regarding radiation exposure, sonograms are re-emerging as imaging methods in such situations. OBJECTIVES: To evaluate the role of sonography in detection of calculus in acute ureteric colic. METHODS: Total 384 patients were enrolled. Hydronephrosis was graded as mild, moderate or severe. Calculus was detected as an intraluminal echogenic focus with distal shadowing with twinkling artifact. Number, size and position of the calculi were assessed. Patients were categorized into four groups:I. ureteric colic only II. ureteric colic with hematuria III. ureteric colic with hydronephrosis and IV. ureteric colic with hematuria and hydronephrosis and then the possibility of detection of calculi has been compared among these groups. RESULTS: Out of 384 patients, 254 were found to have calculi ranging between 2.7-27 mm. Nineteen had in the pelvis/ pelviureteric junction, 64 in proximal ureter, 125 in distal ureter, 6 at iliac crossing and 40 at vesicoureteric junction. Two hundred forty one had single and 14 had multiple calculi. Calculus detection is easier in category III and IV patients. The sensitivity and specificity of ultrasonography were 87.98% and 93.07%. Degree of hydronephrosis is strongly correlated with the number of calculi but weakly correlated with the size of the calculus. CONCLUSION: Sonogram can be used in all cases of acute ureteric colic. Hydronephrosis is the most important finding because it paves the way out for the detection of calculus.

Renal impairment among patients with pelvic organ prolapse in a tertiary care center.

BACKGROUND: Pelvic organ prolapse is a multidimensional phenomenon. The manifestations of renal involvement following pelvic organ prolapse ranges from acute to chronic renal failure and may also lead to end stage renal failure. Prolonged duration and its severity in pelvic organ prolapse are responsible for renal impairment. OBJECTIVES: This study will find out the incidence of renal impairment among women with pelvic organ prolapse undergoing surgical management. It will also help to establish the association of renal impairment with degree and duration of pelvic organ prolapse. METHODS: This prospective study includes cases of pelvic organ prolapse who underwent surgical management from the year 2009-2012 in Dhulikhel hospital. Total 140 cases were assessed with age, duration and different symptoms. Clinical examination was done to find out the degree of prolapse and graded according to Baden Walker classification. Urine routine and microscopic examination, renal function test and abdominopelvic sonography were performed routinely. Renal impairment was assessed using hydronephrosis and creatinine clearance. Creatinine clearance was calculated using patient's weight and serum creatinine value by Cockcroft and Gault formula. RESULTS: Among 140 cases, 8 (5.7%) patients had procedentia, 106 (75.7%) had third degree, 22 (15.7%) had second degree, and four (2.8%) patients had first degree uterine prolapse. The mean duration of prolapse was found to be 11.47 years. Total 5 (3.57%) patients had hydronephrosis. Four had moderate and one had severe hydronephrosis. Total 49 (34.1%) patients had moderate to severe renal failure. Forty six (32%) in stage III moderate reduction in creatinine clearance, 2 (1.4%) with severe reduction and 1(0.7%) in end stage renal failure. CONCLUSION: Renal impairment is a common entity among women with pelvic organ prolapse. Both hydronephrosis and degree renal impairment correlates correspondingly with the duration and severity of prolapse.

Nuchal translucency in normal fetus and its variation with increasing crown rump length (CRL) and gestational age.

BACKGROUND: Nuchal translucency (NT) is the fluid collection behind the fetal neck which can be measured by ultrasound at 11-14 weeks of gestation. Increase in the nuchal translucency thickness is associated with various congenital anomalies. OBJECTIVE: To study the relationship between nuchal translucency thickness, crown rump length and gestational age in normal fetus. METHODS: Prospective analytical study conducted on 211 pregnant women from March 2011 to August 2012. Measurement of Nuchal translucency thickness and crown rump length was performed by ultrasound at 11-14 weeks of gestation. The relationship between nuchal translucency thickness, crown rump length and gestational age was studied by using linear regression analysis. RESULTS: The mean CRL was 63.67+13.48mm (range 41.2-88mm) and mean NT thickness was 1.55+0.35mm (range 0.8-2.7mm), respectively. The median gestational age was 12.9 weeks. The regression equation which shows relation between median NT thickness and CRL was described as follows: expected NT thickness = 0.013CRL+0.725, (R2 = 0.258, p <0.001). There was increase in the incidence of NT thickness more than or equal to 2.5mm; 1.7% in fetus between 12-12.9 weeks of gestation to 15.1% in fetus between 14.0-14.9 weeks. CONCLUSION: Our study offers normative data of NT thickness in normal fetus, which can be used as reference to screen various chromosomal and congenital abnormalities between 11- 14 weeks of gestation. NT thickness increased with increasing CRL and a false positive rate increases with increasing gestational age.

Role of ultrasound as compared with ERCP in patient with obstructive jaundice.

BACKGROUND: The diagnosis of obstructive jaundice relies on proper history taking, clinical examination, laboratory investigations and different non invasive imaging modalities like Ultrasonography (USG), Cholangio Computed Tomography (CCT), Magnetic resonance Imaging (MRI) with Magnetic Resonance Cholangio Pancreatography (MRCP) and invasive modalities like endoscopic retrograde cholangiography (ERCP) and percutaneous trans hepatic cholangiography (PTC). OBJECTIVE: To compare the role of ultrasound with endoscopic retrograde cholangiography and to determine the major causes of obstructive jaundice in our prospect. METHODS: This was a prospective, analytical study conducted on 88 patients presenting to Department of Radiodiagnosis and Imaging at Dhulikhel Hospital-Kathmandu University hospital from March 2011 to August 2012 with clinical diagnosis of obstructive jaundice. Sonographic evaluation was performed in Siemens acusion x-150 and x-300. The final diagnosis was made by endoscopic retrograde cholangiography and /or surgery and confirmed histopathologically. RESULTS: The most common benign causes of obstructive jaundice were choledocholithiasis (63%), CBD stricture (12.3%), cholangitis (8%) and pancreatitis (6.85%) whereas cholangio carcinoma (6.85%) and carcinoma head of pancreas (4%) comprised of the malignant causes . Ultrasonography had sensitivity of 100% and specificity of 89% in detecting choledocholithiasis. It was found to be 98.78% sensitive and 83.33% specific in cholangiocarcinoma. Similarly in pancreatitis, the sensitivity of ultrasonography was 97.59% and sensitivity was 66.67%. CONCLUSION: Ultrasonography acts as a valuable diagnostic imaging modality in detecting the causes of obstructive jaundice. Due to its easy availability, non invasive nature and cost effectiveness, it can be considered as the first line imaging technique/ tool. ERCP is the invasive imaging tool and can be used for both diagnostic and therapeutic purpose.

Cyclin-dependent kinase inhibitor, P276-00, inhibits HIF-1α and induces G2/M arrest under hypoxia in prostate cancer cells.

BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a master regulator of the transcriptional response to oxygen deprivation and controls genes involved in glycolysis, angiogenesis, migration and invasion. Overexpression of HIF-1α has been demonstrated in many common human cancers. METHODS: Luciferase reporter gene assay under hypoxia and normoxia was used to demonstrate transcriptional inhibition of HIF-1 by P276-00. Detailed studies such as western blotting, reverse-transcriptase-PCR and immunofluorescence were carried out to elucidate its mechanism of action. Cytotoxic potential of P276-00 under normoxia and hypoxia was determined on prostate cancer cells using CCK-8 assay, and cell-cycle analysis was carried out using flow cytometry. Antiangiogenic activity of P276-00 was demonstrated by migration assay and tube-formation assay. Efficacy study of P276-00 was performed in a PC-3 xenograft model. RESULTS: P276-00 inhibits transcriptional activation of HIF-1 under hypoxia. It suppressed hypoxia-mediated nuclear HIF-1α expression, as well as phosphorylation of Akt and 4E-BP1 and abrogated expression of HIF-1-inducible gene viz. vascular endothelial growth factor. Under hypoxia, P276-00 did not exhibit enhanced cytotoxic activity in prostate cancer cells but arrested them in the G2/M phase of the cell cycle. The tubular formation of human umbilical vein endothelial cells and migration of prostate cancer cells were also inhibited by P276-00 in vitro. In addition, it demonstrated significant in vivo efficacy in the PC-3 xenograft model. CONCLUSIONS: Given its low toxicity profile, its demonstrated antitumor activity and its potential to inhibit the HIF-1 pathway, P276-00 should be considered as antiangiogenic chemotherapy for prostate cancer.

Sonographic measurement of fetal pinna length in normal pregnancies.

BACKGROUND: Many studies have emphasized on fetal pinna measurements and morphologic features to use this structure as an additional marker for fetal chromosomal anomaly. OBJECTIVES: To assess relationship between fetal pinna length and gestation age and develop a nomogram. To assess relationship between fetal pinna length and head circumference and biparietal diameter. METHODS: Fetal pinna measurements from the tip of helix to the end of lobe were obtained prospectively in 850 singleton pregnant women between 15 and 40 weeks gestation Normal case was defined as normal sonographic findings during examination and normal infant examination at birth or both. Final study population was 787. The relationship between gestational age in weeks to pinna length in millimeters was analyzed by simple linear regression. Correlation of fetal ear length measurements with gestational age, biparietal diameter and head circumference were also obtained. RESULTS: Linear relationships were found between fetal pinna length and gestational age [Pinna Length (mm)=1.044xGestational age (weeks) -3.857]. A nomogram of normal pinna length was obtained. High correlation was found between pinna length and gestational age (r=0.942; p less than 0.001), pinna length and head circumference (r=0.931; p less than 0.001). Significant correlation was found between pinna length and biparietal diameter (r=0.934; p=0.004) CONCLUSIONS: The results of this study provide a nomogram for fetal pinna. The study also provides relationship and good correlation between pinna length and other biometric measurements.