One pot synthesis, in silico study and evaluation of some novel flavonoids as potent topoisomerase II inhibitors.

A library of novel flavonoid derivatives with diverse heterocyclic groups was designed and efficiently synthesized. Structures of the newly synthesized compounds 4a-i and 8a-l have been characterized by 1H NMR, 13C NMR, MS and elemental analysis. Anticancer activities were evaluated against MCF-7, A549, HepG2 and MCF-10A by MTT based assay. Compared with the positive control Adriamycin, compounds 4a, 4b, 4c, 4d, 8d, 8e and 8j were found to be most active anti-proliferative compounds against human cancer cell line. We found that compounds 4a and 4c exhibited inhibition of enzyme topoisomerase II with IC50 values 10.28 and 12.38 µM, respectively. In silico docking study of synthesized compounds showed that compounds 4a and 4c have good binding affinity toward topoisomerase IIα enzyme and have placed in between DNA base pair at active site of enzyme. In silico ADME prediction results that flavonoid coumarin analogues 4a-i could be exploited as an oral drug candidate.

Paediatric intra-axial posterior fossa tumours: pictorial review.

Paediatric brain tumours commonly arise in the posterior cranial fossa. Early diagnosis is often challenging due to initial non-specific clinical symptoms, especially in very young children. The typical MR features of tumours in this region including medulloblastoma, ependymoma, juvenile pilocytic subtype of cerebellar astrocytoma, brain stem glioma and atypical teratoid-rhabdoid tumour are illustrated. Diffusion-weighted imaging and apparent diffusion coefficient values combined with signal characteristics on conventional MR sequences can usually differentiate low-grade from high-grade tumours. Prompt diagnosis is crucial as total surgical resection, which is only possible in localised disease, improves prognosis. A practical MR flow chart is introduced for differentiating different types of posterior cranial fossa tumours, which might be useful in clinical practice.

US assessment of medial arterial calcification: a sensitive marker of diabetes-related microvascular and macrovascular complications.

PURPOSE: To examine the sensitivity of ultrasonography (US) compared with conventional radiography in detection of lower limb (thigh) medial arterial calcification (MAC) in type 2 diabetic patients and evaluate its association with diabetes-related complications. MATERIALS AND METHODS: The study was approved by the local research ethics committee, and informed written consent was obtained. US was performed in 289 patients with type 2 diabetes mellitus, and MAC severity was assigned a score from 0 to 8. Among the patients, 263 underwent radiographic examinations. All subjects underwent clinical evaluation to detect the presence of diabetes-related complications. RESULTS: US helped detect MAC in more subjects compared with radiography (65.8% vs 12.2%). US helped detect MAC from mild (scores 1-4) to severe (scores 5-8) degrees, while mild degree of MAC was poorly demonstrated with radiography. The incidence of nephropathy, retinopathy, sensory neuropathy, and macrovascular complications increased with the severity of MAC (based on US scoring). With univariate analysis, the presence of MAC was associated with nephropathy (P<.001), retinopathy (P<.001), sensory neuropathy (P=.004), and macrovascular complications (P<.001). After adjustment for potential confounders, the presence of severe MAC was associated with nephropathy, retinopathy, and macrovascular complications, with the odds ratios of 3.4 (95% confidence interval [CI]: 1.53, 7.43; P=.003), 2.6 (95% CI: 1.22, 5.32; P=.013), and 3.8 (95% CI: 1.37, 10.6; P=.01), respectively. CONCLUSION: In type 2 diabetic Chinese patients, US was more sensitive than conventional radiography in the detection of MAC, particularly when the MAC was mild. The presence of severe MAC was associated with diabetic nephropathy, retinopathy, and macrovascular complications. US detection of MAC was a potential early marker to identify diabetes-related complications.

Imaging in children presenting with acute neurological deficit: paediatric stroke mimics.

Stroke mimics refer to conditions manifesting with neurologic deficits without underlying cerebrovascular diseases. Major causes in the paediatric population under this category include infections, inflammation, demyelination, neoplasm, drug related, phacomatosis, and miscellaneous disorders. These conditions and their respective imaging findings are briefly discussed here.

Imaging in children presenting with acute neurological deficit: stroke.

Neurological deficits in the paediatric age group are much rarer than in adults; however, it is an urgent condition that relies heavily on imaging for a prompt accurate diagnosis. Neurological deficits caused by cerebrovascular diseases are defined as stroke, whereas conditions manifesting with neurological deficits without underlying cerebrovascular diseases are referred to as stroke mimics. To the best of the authors' knowledge, there is a lack of systematic pictorial review that collectively describes the imaging of neurological deficit in children. The purpose of the present series is to discuss the causes and imaging appearance of neurological deficits in childhood, based on the experience of a tertiary paediatric referral centre These are broadly categorised into stroke, infection, inflammation, metabolic disorder, cerebral neoplasms and drug poisoning. Different entities of stroke and their respective imaging findings are discussed. Paediatric stroke can further be divided into arterial ischaemic stroke, sino-venous stroke, haemorrhagic stroke and hypoxic-ischaemic encephalopathy.

Primary spinal cord desmoplastic astrocytoma in an adolescent: a rare tumour at rare site and rare age.

We report a case of a non-infantile primary intramedullary spinal cord desmoplastic astrocytoma in an 18-year-old girl who presented with spastic paraparesis. The patient had been unable to run for 1 year. Magnetic resonance imaging of her spine showed an intramedullary solid and cystic heterogeneously enhancing lesion located at T7-T8 level. Partial excision was performed. Histology revealed a desmoplastic astrocytoma. To the best of our knowledge, there is no report on primary desmoplastic astrocytoma of the spinal cord in literature. Nor has such a symptomatic tumour manifesting at the age of 18 years been documented.

Contemporary concepts in treatment planning, reconstruction and rehabilitation of the maxillofacial region: an overview of methods used in practice.

Treatment planning, reconstruction and rehabilitation of maxillofacial and dental defects have always been a challenge for a maxillofacial surgeon. Reconstruction of the oral cavity is often a difficult task as it involves the restoration of both the esthetic or cosmetic form as well as the preoperative function. Understanding the oral cavity anatomy as well the functional capacities of its various subunits is required to achieve good results. The recent advances in treatment planning, diagnostic imaging and reconstructive techniques, especially in the field of osseointegration, tissue expanders, perforator flaps, microvascular free tissue transfer and bone engineering, have yielded excellent functional and esthetic outcomes. This article provides a brief overview on various advanced reconstructive and rehabilitation techniques available in contemporary clinical practice.

Intravascular papillary endothelial hyperplasia: report of two cases.

Intravascular papillary endothelial hyperplasia is a rare benign vascular proliferative process as a result of papillary proliferation of the endothelial cells within the vascular lumen. We report two cases of intravascular papillary endothelial hyperplasia affecting the extremities. The characteristic sonological and MR imaging features are discussed, with updated review of literature. Imaging features are helpful in achieving a definitive diagnosis of the intravascular papillary endothelial hyperplasia.

Asynchronous neuro-osseous growth in adolescent idiopathic scoliosis--MRI-based research.

Adolescent idiopathic scoliosis (AIS) is a common worldwide problem and has been treated for many decades; however, there still remain uncertain areas about this disorder. Its involvement and impact on different parts of the human body remain underestimated due to lack of technology in imaging for objective assessment in the past. The advances in imaging technique and image analysis technology have provided a novel approach for the understanding of the phenotypic presentation of neuro-osseous changes in AIS patients as compared with normal controls. This review is the summary of morphological assessment of the skeletal and nervous systems in girls with AIS based on MRI. Girls with AIS are found to have morphological differences in multiple areas including the vertebral column, spinal cord, skull and brain when compared with age- and sex-matched normal controls. Taken together, the abnormalities in the skeletal system and nervous system of AIS are likely to be inter-related and reflect a systemic process of asynchronous neuro-osseous growth. The current knowledge about the anatomical changes in AIS has important implications with respect to the understanding of fundamental pathomechanical processes involved in the evolution of the scoliotic deformity.

Pulmonary metastases in children with osteosarcoma: characteristics and impact on patient survival.

BACKGROUND: Approximately 15-20% of patients with osteosarcoma present with detectable metastatic disease and the majority of whom (85%) have pulmonary lesions as the sole site of metastasis. Previous studies have shown that the overall survival rate among patients with localized osteosarcoma without metastatic disease is approximately 60-70% whereas survival rate reduces to 10-30% in patients with metastatic disease. OBJECTIVE: To determine the incidence and characteristic features of pulmonary metastases in a group of osteosarcoma patients and correlate the findings with the prognostic outcome/survival. MATERIALS AND METHODS: Seventy-seven cases of histologically confirmed osteosarcoma were reviewed (47 male, 30 female, mean age 10.9). The site and size of the primary tumour and degrees of chemonecrosis were recorded. Lung metastases were analyzed according to their size, number, distribution and interval from diagnosis. The Kaplan-Meier method was used to analyze the survival probability curve. Significant differences (P < 0.05) were evaluated with the log-rank test for univariate analyses. RESULTS: Seventeen patients had synchronous and 11 had metachronous lung metastases. Sixteen (57%) underwent pulmonary metastasectomy. Nine of sixteen (56%) patients with metastasectomy and 10/12 (83%) patients without metastasectomy died. Poor chemonecrosis was associated with a worse outcome. Number, distribution and timing of lung metastases, but not the size of lung metastases, were of prognostic value for survival. CONCLUSION: Radiological detection of lung metastases is clinically important as it indicates a worse prognosis.

Malignant pigmented clear cell epithelioid cell tumor (PEComa) in an adolescent boy with widespread metastases: a rare entity in this age group.

Malignant pigmented clear cell epithelioid cell tumor of the kidney is a rare variant of perivascular epithelioid cells tumors (PEComa) or epithelioid angiomyolipoma (AML). PEComa is characteristically composed purely of epitheloid cells. The fat cells and the blood vessels that are typical of classic AML are absent. Most epithelioid AML cases are benign; however, malignant epithelioid AML of the kidney has been occasionally reported in adults in association with tuberous sclerosis. We report the radiological-pathological features of a malignant pigmented clear cell epithelioid renal tumor in a 15-year-old boy presenting with extensive metastases but without clinical evidence of tuberous sclerosis.

Primary pleomorphic liposarcoma of bone in an adolescent: imaging features of a rare entity.

We report a rare case of a primary osseous pleomorphic liposarcoma of the distal femur in a 13-year-old boy. Primary liposarcoma of bone is a very rare malignant tumour originating from primitive mesenchymal cells rather than mature adipose tissue. Pleomorphic liposarcoma is the least common of the eight known histological subtypes in the WHO classification. The entity is not previously reported in children. This is the third reported case of pleomorphic liposarcoma of the bone, and the first reported case presenting in adolescence. We describe the computed tomography and magnetic resonance imaging features of this rare bony tumour.

Dynamic ultrasound study on urinary bladder in infants with antenatally detected fetal hydronephrosis.

UNLABELLED: To evaluate bladder function in infants with antenatally diagnosed hydronephrosis (ANH) using dynamic ultrasound protocol. Forty consecutive male infants (mean, 0.25 y) with ANH and 33 age-matched normal controls (mean, 0.49 y) were recruited. Anteroposterior (AP) diameter of renal pelvis (RP) and hydronephrosis index [HI = anteroposterior diameter of RP of kidney divided by urinary bladder volume (BV)] were calculated. Maximum BV (MaxBV) was determined just before voiding. Residual volume (RV) and bladder wall thickness (BWT) were measured after spontaneous voiding. Thirty-one infants (77.5%) showed persistently dilated RP postnatally in which 12 (39%) showed significantly high HI. In general, ANH infants had smaller MaxBV (30.71 versus 52.45 mL), larger residual volume (2.47 versus 1.93 mL), and larger BWT (4.4 versus 3.7 mm) than normal (p < 0.05, Mann-Whitney test). Infants with abnormally high HI had significantly more disturbed bladder parameters [smaller MaxBV (23.33 versus 33.49 mL) and larger BWT (4.67 versus 3.79 mm)] than the normal HI group (p < 0.05, Mann-Whitney test). Abnormal functional bladder parameters were evident in ANH infants. We postulated that immature function in the pelviureteric junction was associated with bladder dysfunction in these infants. Dynamic ultrasound protocol might help to understand the underlying pathophysiology of urinary system in ANH infants. ABBREVIATIONS: :

Inflammatory myofibroblastic tumour: an imaging dilemma (2010: 5b). IMFT of the bladder.

Inflammatory myofibroblastic tumour (IMFT) is a distinct entity under the group of inflammatory pseudotumours. Sometimes these pseudotumours can have an aggressive appearance on imaging, which makes it indistinguishable from other malignant neoplasms. We present a case of IMFT of the bladder in a child.

Evaluation of real-time qualitative sonoelastography of focal lesions in the parotid and submandibular glands: applications and limitations.

OBJECTIVE: To evaluate qualitative ultrasound elastography for focal salivary gland masses identified during routine clinical practice. METHODS: Sixty-five parotid or submandibular masses in 61 patients underwent real-time qualitative ultrasound elastography and were scored on colour-scaled elastograms in terms of their stiffness relative to adjacent normal salivary parenchyma from ES 1 (soft) to ES 4 (stiff). This was correlated with diagnosis from aspiration cytology or histology. RESULTS: There were 29 Warthin's tumours (WTs), 23 pleomorphic adenomas (PAs), 2 adenoid cystic carcinomas, 1 adenosquamous carcinoma, 1 nodal metastasis from nasopharyngeal carcinoma, 1 lymphoma (2 deposits), 3 Kuttner tumours and 4 cases of Kimura's disease. ES scores showed clustering according to pathological condition. In this respect, PAs were firmer than WTs (P < 0.004, Fisher's exact test). Nine, 19, 14 and 17 of the benign masses and 0, 1, 2 and 3 of the malignant masses were ES 1, 2, 3 and 4 respectively. All three primary salivary malignancies were ES 4 compared with 1/29 WTs and 16/23 PAs. CONCLUSION: These preliminary findings suggest that qualitative real-time ultrasound elastography, although an ancillary technique to conventional ultrasound in the salivary glands, is likely to have a poor ability to discriminate benign lesions (particularly PAs) from malignant disease.

Radiological appearance of inflammatory myofibroblastic tumour.

Inflammatory myofibroblastic tumour (IMFT) is a distinct entity with variable clinical presentation and therapeutic options. We present three paediatric cases of IMFT, originated from the lung, bladder and ovary respectively. All lesions were heterogeneous, with mixed solid/cystic components and infiltrative pattern, and were interpreted as aggressive malignant neoplasms initially due to their bizarre imaging appearance. The definitive diagnosis was derived from characteristic histopathological features.

A pictorial review of imaging of abdominal tumours in adolescence.

Neoplastic abdominal tumours, particularly those originating from embryonal tissue (such as hepatoblastoma and nephroblastoma) and neural crest cells (such as neuroblastoma), are well-documented in young children. Neoplasms of adulthood, most commonly carcinoma of different visceral organs, are also well-documented. Abdominal tumours in adolescence constitute a distinct pathological group. The radiological features of some of these tumours have been described only in isolated reports. The purpose of this pictorial essay was to review the imaging findings of various kinds of abdominal tumours in adolescent patients (with an age range of 10-16 years) who presented to the Children Cancer Center of our institution in the past 15 years. Some tumours, though rare, have characteristic imaging appearances (especially in CT) that enable an accurate diagnosis before definite histological confirmation.

Oesophageal haemangioma: imaging characteristics of this rare condition.

Oesophageal haemangiomas are rare, benign, vascular tumours that have characteristic features on computed tomography and magnetic resonance imaging. This enables radiologists to suggest the correct diagnosis without the need for invasive biopsy. Diagnostic characteristics include phleboliths seen on computed tomography, and intense homogeneous enhancement of the lesion on magnetic resonance imaging. These tumours have life-threatening haemorrhagic potential and therefore require surgical resection.

An institutional review of paediatric haemangiomas: prevalence, imaging features, and outcomes.

OBJECTIVE: To review the demographic data, imaging features, and outcomes of paediatric haemangiomas. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS: A total of 58 children diagnosed with haemangioma between 1998 and 2007. MAIN OUTCOME MEASURES: Demographic data, imaging features, type of treatment received, and outcomes. RESULTS: In all, 19 (33%) of these patients were males and 39 (67%) were females. Most of the lesions (64%) were in the head and neck region. Three (5%) of the patients were complicated by the Kasabach-Merritt syndrome; 21 underwent no imaging, and 37 had ultrasound and/or magnetic resonance imaging. In the majority (85%), ultrasound of the lesions revealed mixed echogenicity and/or phleboliths with variable colour Doppler patterns. On magnetic resonance imaging, most (87%) of the lesions were T1 iso- to hypo-intense and T2 hyperintense with slight heterogeneous signalling and revealed presence of central flow voids (vascular channels) or low-signal areas (fibrous tissue or calcification). In all, 85% appeared homogeneous while 15% showed heterogeneous enhancement. Of 58 patients, 39 (67%) patients received conservative treatment; the lesions resolved spontaneously in 34 (87%) patients, enlarged in 2 (5%), and remained static in 3 (8%). Interventions were directed at the lesions in 19 patients. These entailed surgical excision (n=7), argon laser therapy (n=3), and medical treatment (n=9). Of the latter patients, treatment included: systemic steroids (n=5), interferon (n=1), steroids and interferon (n=1), vincristine (n=1), and sclerotherapy (n=1). Partial or complete resolution of the lesions ensued in 15 (79%) of the patients, while their size remained static in four (21%). CONCLUSION: Though ultrasound and magnetic resonance imaging features varied, the diagnosis of most haemangiomas could be confidently made by imaging. About 33% of haemangiomas underwent surgical/medical interventions, for which imaging was useful to monitor post-treatment progress.

Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans.

Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret's meningitis that each carry a rare monoallelic variant in the autophagy proteins ATG4A or LC3B2. HSV2-activated autophagy was abrogated in patient primary fibroblasts, which also exhibited significantly increased viral replication and enhanced cell death. HSV2 antigen was captured in autophagosomes of infected cells, and genetic inhibition of autophagy by disruption of autophagy genes, including ATG4A and LC3B2, led to enhanced viral replication and cell death in primary fibroblasts and a neuroblastoma cell line. Activation of autophagy by HSV2 was sensitive to ultraviolet (UV) irradiation of the virus and inhibited in the presence of acyclovir, but HSV2-induced autophagy was independent of the DNA-activated STING pathway. Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.