Flavonoids as a scaffold for development of novel anti-angiogenic agents: An experimental and computational enquiry.

Relationship between structural diversity and biological activities of flavonoids has remained an important discourse in the mainstream of flavonoid research. In the current study anti-angiogenic, cytotoxic, antioxidant and cyclooxygenase (COX) inhibitory activities of diverse class of flavonoids including hydroxyl and methoxy substituted flavones, flavonones and flavonols have been evaluated in the light of developing flavonoids as a potential scaffold for designing novel anti-antiangiogenic agents. We demonstrate anti-angiogenic potential of flavonoids using in vivo chorioallantoic membrane model (CAM) and further elaborate the possible structural reasoning behind observed anti-angiogenic effect using in silico methods. Additionally, we report antioxidant potential and kinetics of free radical scavenging activity using DPPH and SOR scavenging assays. Current study indicates that selected flavonoids possess considerable COX inhibition potential. Furthermore, we describe cytotoxicity of flavonoids against selected cancer cell lines using MTT cell viability assay. Structural analysis of in silico docking poses and predicted binding free energy values are not only in accordance with the experimental anti-angiogenic CAM values from this study but also are in agreement with the previously reported literature on crystallographic data concerning EGFR and VEGFR inhibition.

Long-term outcome of Fowler-Stephens orchiopexy in boys with prune-belly syndrome.

PURPOSE: Intra-abdominal testes in boys with prune-belly syndrome have been conventionally managed by 1 or 2-stage orchiopexy with division of the gonadal vessels. We reviewed a series of adults with prune-belly syndrome to assess the morphological and functional outcome of orchiopexy in childhood with specific reference to the spontaneous onset of puberty, hormonal profiles and sexual function. MATERIALS AND METHODS: A total of 41 boys were divided into 3 groups depending on the type of orchiopexy performed, namely group 1-20 with bilateral 1-stage orchiopexy, group 2-10 with unilateral 1-stage and contralateral 2-stage orchiopexy, and group 3-11 with bilateral 2-stage orchiopexy. RESULTS: In group 1 9 of 20 patients had good scrotal testes bilaterally, 6 had a good scrotal testis on 1 side and 3 had small testes on each side. Two boys required testosterone supplementation but 18 had normal hormonal and sexual function. In group 2 6 of 10 patients had good scrotal testes bilaterally and 4 had a good scrotal testis on 1 side. All patients underwent spontaneous puberty with good sexual function. In group 3 7 of 11 boys had good scrotal testes bilaterally and 3 had 1 good testis with normal puberty and sexual function. These 10 patients underwent spontaneous puberty with good sexual function. CONCLUSIONS: The majority of boys with prune-belly syndrome had a satisfactory outcome after orchiopexy with division of the gonadal vessels with testicular function sufficient to induce puberty and maintain satisfactory sexual function in adult life.

Management of urinary extravasation in 18 boys with posterior urethral valves.

PURPOSE: Urinary extravasation with associated posterior urethral valves is uncommon and published articles are restricted to case reports. We propose a management algorithm on the basis of presentation of 18 boys with this condition. MATERIALS AND METHODS: In this retrospective review we analyze the clinical features, diagnostic radiological imaging (voiding cystourethrogram and (99m)technetium mercaptoacetyltriglycine scan) and measured glomerular filtration rate (GFR) for assessment of renal function in boys presenting with posterior urethral valves and urinary extravasation. Indications for surgical intervention and long-term outcome were evaluated. Results are presented as mean +/- SD. RESULTS: Patient age at presentation was 4 days (range 1 to 28). Salient features at presentation were abdominal distention in 55.5% of cases, flank mass in 55.5%, respiratory distress in 16.6% and septicemia in 22.2%. Patients were categorized into group 1 with ascites (6 boys) and group 2 without ascites (12). Followup was 70.8 +/- 5.6 months. In group 1 the 3 boys with ascites alone had a followup GFR of 29 versus 74 ml. per minute per 1.73 m.2 in 3 with urinoma plus ascites (p = 0.001) at 64 +/- 4.9 months. In group 2 the GFR in 3 boys with bilateral urinoma was 104.7 +/- 30.4 versus 54.3 +/- 29.4 ml. per minute per 1.73 m.2 in the other 9 with unilateral urinoma (p = 0.001) at 36 +/- 4.2 and 81.3 +/- 4.7 months, respectively. The ipsilateral kidney showed reduced function in 6 of 12 boys with unilateral urinoma from both groups. CONCLUSIONS: Renal function on the side of the urinoma is impaired, and the majority of patients have impaired global renal function. A management algorithm is proposed.

Functioning adrenocortical neoplasms in children.

OBJECTIVE: To describe the clinical features, treatment and outcome of functioning adrenocortical tumours in children, and to assess the value of tumour size as a marker for malignant potential. PATIENTS AND METHODS: Twenty-one children (mean age at presentation 4.9 years, range 0.6-11; 12 girls and nine boys) who presented with a functioning adrenal mass over a 29-year period (1972-2000) were assessed. Clinicopathological features and outcome information were obtained from a structured review of the case-notes. Before 1980 the diagnosis and staging was mainly obtained by intravenous pyelography and plain X-ray. Since 1980, ultrasonography, computed tomography and more recently magnetic resonance imaging were the methods of choice. RESULTS: The mean (range) duration of symptoms before diagnosis was 31 (2-108) months. The symptoms and signs at presentation comprised virilization (18 children), Cushingoid features (three), precocious puberty (three) and hypertension (four). Three children had malignant neoplasms, one presented with metastasis and of the other two, one died from the disease within 6 months, despite adjuvant chemotherapy and radiotherapy. The third girl is disease-free 11 years after complete excision of the neoplasm. Eighteen children had a benign neoplasm and all are alive and free of recurrence. In most of the children surgical extirpation was relatively simple, blood loss minimal, recovery uneventful and the hospital stay short (mean 5 days). The virilizing effects of all the neoplasms gradually resolved after surgery within a median (range) of 27 (6-108) months. CONCLUSIONS: Functioning adrenocortical neoplasms in children are rare, with a peak incidence in the first decade, are predominantly unilateral and more common in girls. Most are benign, but both benign and malignant lesions can present with virilizing and Cushingoid features. The malignant neoplasms have an extremely poor prognosis, especially if excision is incomplete, despite adjuvant chemotherapy and radiotherapy. Although there is an association between tumour size and malignancy, this cannot be used as a reliable individual discriminator.

Choledochal cyst: a report of two cases.

Two cases of choledochal cyst in two female Saudi paediatric patients seen in the last five years are presented. Both presented with recurrent abdominal pain of long duration with no associated palpable abdominal mass or jaundice. They are of Type I, classification showing cystic dilation of the common bile duct. Findings on sonography and computed tomography (CT) included a cystic mass in the porta hepatis separate from the gallbladder, non-dilation of intra-hepatic bile ducts and the presence of stones in the cyst in the older child. Both patients underwent operation with intraoperative cholangiography which demonstrated anomalous junction of the pancreatic duct with the common bile duct--a factor implicated in the aetiology of the disease condition.

Childhood achalasia--a case report.

The neuromotor disorders of the oesophagus are rare in childhood. The spectrum includes achalasia, vigorous achalasia and diffuse oesophageal spasm. The classical presentation in achalasia is vomiting, failure to thrive and recurrent chest infection. Diagnosis is confirmed on plain film of the chest and a barium swallow which shows the "bird beak" sign. Surgery is the preferred mode of management in children. Adjunctive procedures to surgery like Nissen fundoplication should be selectively performed.

Embryonal rhabdomyosarcoma within a choledochal cyst.

The authors describe a 6-year-old girl in whom they found an embryonal rhabdomyosarcoma in a choledochal cyst; they found no previous reports of such an association. The patient presented with recurrent jaundice and loss of weight and appetite. A large abdominal mass was palpable. Ultrasonography and computed tomography revealed a large subhepatic mass, which contained multiple septations and mural masses delineating cystic areas. The common hepatic duct opened directly into the mass, and the intrahepatic radicles were dilated. Intraoperative cholangiography revealed that the cysts in the mass were continuous with the hepatic and intrahepatic radicles. The mass was completely excised, and a Roux-en-Y hepaticojejunostomy was performed. Postoperative adjunct chemotherapy and radiotherapy were instituted.

Gastric torsion: Not such a rare entity.

We describe seven patients who suffered chronic gastric torsion, seen during a 28-month period. Four were children, of which three were infants. The infants had projectile vomiting and two also had failure to thrive. The adults presented with epigastric pain and vomiting. Upper gastrointestinal series clinched the diagnosis in all patients. The classic radiographic presentation of a stomach lying across the epigastrium with the cardia and fundus in a dependent position to the body of the stomach and pylorus may be overlooked in some cases. Choice of surgical procedure in its management has been discussed. There was no associated abnormality in four of the six operated cases. One infant had an atretic bowel, vascular anomalies, umbilical hernia, and previous meconium peritonitis; a second infant had jejunojejunal intussusception. A high index of suspicion is warranted in patients presenting with recurrent abdominal pain or in infants with unexplained vomiting and failure to thrive. Upper gastrointestinal series in adults should preferably be performed while the pain is present.