Spontaneous Arachnoid Cyst Rupture with Subdural Hygroma in a Child.

Arachnoid cyst of the brain is common in children but its association with spontaneous subdural hygroma is rare. A case of a nine-year-old boy, without any preceding history of trauma, is presented here who came to the emergency department of a tertiary care hospital with complaints of headache, nausea, and vomiting for the last two weeks but more for the last two days. Examination showed a young, fully conscious oriented boy with positive Cushing's reflex and papilledema of left eye. MRI (magnetic resonance imaging) of the brain showed left temporal extra-axial cystic lesion of 5.40 × 4.10 cm in size, representing arachnoid cyst, with bilateral frontoparietal subdural hygromas. Cyst was partially drained through left temporal craniectomy and subdural hygromas were drained through bilateral frontal burr holes. Postoperatively the child recovered uneventfully and was discharged on the seventh postoperative day. Histopathology proves it to be arachnoid cyst of the brain with subdural CSF (cerebrospinal fluid) collection or hygroma.

Inter-observer variability in diagnosing radiological features of aneurysmal subarachnoid hemorrhage; a preliminary single centre study comparing observers from different specialties and levels of training.

BACKGROUND: A noncontrast computed tomography (CT) scan remains the initial radiological investigation of choice for a patient with suspected aneurysmal subarachnoid hemorrhage (aSAH). This initial scan may be used to derive key information about the underlying aneurysm which may aid in further management. The interpretation, however, is subject to the skill and experience of the interpreting individual. The authors here evaluate the interpretation of such CT scans by different individuals at different levels of training, and in two different specialties (Radiology and Neurosurgery). METHODS: Initial nonontrast CT scan of 35 patients with aSAH was evaluated independently by four different observers. The observers selected for the study included two from Radiology and two from Neurosurgery at different levels of training; a resident currently in mid training and a resident who had recently graduated from training of each specialty. Measured variables included interpreter's suspicion of presence of subarachnoid blood, side of the subarachnoid hemorrhage, location of the aneurysm, the aneurysm's proximity to vessel bifurcation, number of aneurysm(s), contour of aneurysm(s), presence of intraventricular hemorrhage (IVH), intracerebral hemorrhage (ICH), infarction, hydrocephalus and midline shift. To determine the inter-observer variability (IOV), weighted kappa values were calculated. RESULTS: There was moderate agreement on most of the CT scan findings among all observers. Substantial agreement was found amongst all observers for hydrocephalus, IVH, and ICH. Lowest agreement rates were seen in the location of aneurysm being supra or infra tentorial. There were, however, some noteworthy exceptions. There was substantial to almost perfect agreement between the radiology graduate and radiology resident on most CT findings. The lowest agreement was found between the neurosurgery graduate and the radiology graduate. CONCLUSION: Our study suggests that although agreements were seen in the interpretation of some of the radiological features of aSAH, there is still considerable IOV in the interpretation of most features among physicians belonging to different levels of training and different specialties. Whether these might affect management or outcome is unclear.

Squamous cell carcinoma of external auditory canal lacking epidermal growth factor receptor protein overexpression, in an elderly Omani with oculocutaneous albinism treated with palliative radiotherapy.

We report a case of squamous cell carcinoma of external auditory canal in an Omani man with oculocutaneous albinism. The disease mimicked inflammatory process revealing positive cultures for various microorganisms during the course of his illness. He was eventually biopsied to rule out atypical infective process or presence of malignancy. He was staged as T4N0M0 and treated with radical doses of palliative radiation therapy which was very well tolerated and resulted in a complete resolution of disease clinically and a major soft tissue response on radiological imaging. Another unique finding was the absence of epidermal growth factor receptor (EGFR) protein overexpression in the tumour specimen. More than 90% of mucosal squamous cell carcinoma (SCC) involving the head and neck region overexpress the EGFR protein in normal skin patients. SCC is the predominant cutaneous malignancy in albinos, and the presence of EGFR protein overexpression in cutaneous SCC is believed to be 56-58% in normal skin patients. The scientific literature is scarce on reporting incidence of EGFR overexpression in either cutaneous or mucosal SCC in albinos, and it remains to be defined whether being albino is the cause for its absence.

Supratentorial extraventricular anaplastic ependymoma in a child.

A young child presented to the emergency department of a tertiary care hospital with on and off headache, focal seizures involving the left side of the body, weakness of left upper and lower limbs and vomiting for 2 weeks. Examination showed an alert child with grade 4/5 powers in left upper and lower limbs. Blood investigations were normal. An urgent CT of the brain showed intra-axial mass in the right frontal cerebral cortex, superolateral to the right lateral ventricle. MRI of the brain showed supratentorial extraventricular mass of 5.20 × 3.70 × 3.80 cm, in the right frontal cortex, emitting heterogeneous signals on T1, T2 and fluid-attenuated inversion recovery sequences and impression of astrocytoma, ependymoma or choroid plexus papilloma was made. Complete surgical resection of mass was performed. Histopathology of the mass proved it as WHO grade III anaplastic ependymoma. The child made an uneventful postoperative recovery and radiotherapy was followed.

Peptide arrays for development of PDGFRß Affine molecules.

PURPOSE: Peptide arrays represent an attractive method for identification of amino acid motifs that bind to target structures. Spotting derivatives of the linear peptide platelet-derived growth factor receptor (PDGFR)-P1, which has been identified to bind the extracellular domain of the platelet-derived growth factor receptor beta, allows the synchronous investigation of the target affinity of numerous ligands. PROCEDURES: A peptide array randomizing PDGFR-P1 was constructed by replacement of each amino acid by all 20 natural amino acids. Incubation of the array with PDGFRß and fibroblast growth factor receptor as negative control target was performed. Selected derivatives and fragments of PDGFR-P1 were chemically synthesized, radiolabeled, and evaluated in cell-based assays, using human pancreatic carcinoma BxPC3 and human breast cancer MCF7 cells. RESULTS: Binding capacity was increased for the derivate yG2 by exchange of 7S to 7R. Competition experiments demonstrated a binding decrease with increasing competitor concentration. Serum stability of yG2 was improved compared to the native ligand. CONCLUSION: Peptide arrays were successfully applied for the improvement of the PDGFRß binding peptide PDGFR-P1.

Screening of a novel peptide targeting the proteoglycan-like region of human carbonic anhydrase IX.

The extracellular domain of human carbonic anhydrase IX (CA IX) is extended by a proteoglycan-like region (PGLR). The aim of the present study was the development of novel molecules with specificity for PGLR, which may be used for tumor targeting and imaging. PGLR was chemically synthesized, and phage display biopanning was performed. The identified ligand PGLR-P1 was labeled with 125I and characterized for target binding and metabolic stability. In vitro characterization included kinetic, competition, and internalization studies on CA IX-positive renal cell carcinoma SKRC 52 cells. The CA IX-negative cell lines HEK293 wt and BxPC3 were used as negative controls. In vitro binding experiments revealed an increasing affinity of 125I-PGLR-P1 to SKRC 52 cells but not to negative control HEK293 wt and BxPC3 cells. Internalization studies indicated an exclusive cell membrane binding. Biodistribution analysis demonstrated a higher accumulation in SKRC 52 tumors than in most normal tissues after perfusion. In vivo blocking led to a significant decrease in tumor uptake. Our findings indicate that PGLR-P1 is a promising lead structure for the development of new peptide-based ligands targeting the PGLR of CA IX and reveal challenges that need to be considered for peptide-related molecular imaging.

Binding of the phage display derived peptide CaIX-P1 on human colorectal carcinoma cells correlates with the expression of carbonic anhydrase IX.

Phage display represents an attractive screening strategy for the identification of novel, specific binding ligands that could be used for tumor targeting. Recently, a new peptide (CaIX-P1) with affinity for human carbonic anhydrase IX (CAIX) was identified and evaluated. The aim of the present study is to characterize the properties of CaIX-P1 for targeting human colorectal carcinoma and investigate the correlation of peptide binding with the expression of carbonic anhydrase IX. Human colorectal carcinoma HCT116 and HT29 cells were investigated for CAIX expression using Western Blot analysis. Binding and competition studies of 125I-radiolabeled CaIX-P1 were performed on HCT116 cells in vitro. FACS analysis and fluorescence microscopy studies were carried out after cell incubation with fluorescein-labeled CaIX-P1 and rhodamine-labeled anti-human CAIX-mAb. Our studies revealed an enhanced in vitro expression of carbonic anhydrase IX in HCT116 and HT29 cells with increasing cell density. Binding of 125I-labeled-CaIX-P1 on HCT116 cells increased with increasing cell density and correlated to the CAIX expression. FACS analysis demonstrated a correlation of cell labeling between FITC-CaIX-P1 and rhodamine-labeled anti-CAIX-mAb in both HCT116 and HT29 cells. The results of our study indicate that the phage display identified peptide CaIX-P1 might be an attractive candidate for the development of a ligand targeting CAIX in colorectal cancer.

Rare co-occurrence of dural arteriovenous fistula and arteriovenous malformation with bilateral subcortical and basal ganglia calcification.

The present study describes the imaging findings in a patient with dural arteriovenous fistula (AVR) and arteriovenous malformation (AVM) with bilateral subcortical and basal ganglia calcification. A 29 year old male patient presented with chief complaint of recent onset of generalized tonic clonic seizures and mild disorientation. The imaging studies on MCT demonstrated diffuse, symmetric calcification in the bilateral basal ganglia and subcortical white matter. MR imaging and angiography revealed AVM in parietooccipital region with supply predominantly from left posterior cerebral and middle cerebral arteries. Multiple dural feeders from meningeal branches of occipital and superficial temporal branches of bilateral external carotid and right internal carotid arteries. Calcification is proposed to be due to chronic reflux into the parenchymal veins or vascular steal phenomenon. This rare co-occurrence of subcortical calcification in a patient with a dural AVF and AVM is being reported.

An institutional review of transarterial embolization in haemorrhagic urological emergencies.

OBJECTIVE: To review the effectiveness of therapeutic transarterial embolization in controlling phagic urological emergencies irrespective of the cause of emergencies. METHODS: Thirty-seven vascular angiographies were performed in 32 patients (19 males and 13 females, age range 19-70 years) who were referred with haemorrhagic urological emergencies to Aga Khan University Hospital's angiography suite from July 2005 to June 2010. Embolization was performed with coils, polyvinyl alcohol particles, N-Butyl cyanoacrylate glue and gel foam according to the clinical indication. Data on clinical indication, technique, site and type of bleeding lesions were obtained from a retrospective review of medical records. Success rate, clinical outcome and complications of the procedure were analysed. RESULTS: Indications of procedure included iatrogenic injury (16), Renal mass on clinical examination and imaging (4), haematuria with pseudoaneurysm on examination (3), haematuria with no known cause (3), post traumatic renovascular injury (2) Renal arteriovenous fistulas (2), Carcinoma of prostate (1) and pelvic arteriovenous (AV) fistula (1). Twenty four patients underwent successful endovascular control of bleeding. Eight examinations were negative for active extravasation, two of whom showed haemorrhage in second session and were embolized. Two sessions were needed in two patients at different time intervals. Complication as dislodgement of coil in distal profunda femoris artery was seen in one patient with no significant obstruction to flow. CONCLUSION: Transarterial renal angioembolisation is a safe and effective therapeutic tool for managing haematuria or haemorrhage in urological emergencies. Wherever and whenever indicated it should be the first preferred treatment modality.

Optimization of a novel peptide ligand targeting human carbonic anhydrase IX.

BACKGROUND: Carbonic anhydrase IX (CA IX) is a hypoxia-regulated transmembrane protein over-expressed in various types of human cancer. Recently, a new peptide with affinity for human carbonic anhydrase IX (CaIX-P1) was identified using the phage display technology. Aim of the present study is to characterize the binding site in the sequence of CaIX-P1, in order to optimize the binding and metabolic properties and use it for targeting purposes. METHODOLOGY/PRINCIPAL FINDINGS: Various fragments of CaIX-P1 were synthesized on solid support using Fmoc chemistry. Alanine scanning was performed for identification of the amino acids crucial for target binding. Derivatives with increased binding affinity were radiolabeled and in vitro studies were carried out on the CA IX positive human renal cell carcinoma cell line SKRC 52 and the CA IX negative human pancreatic carcinoma cell line BxPC3. Metabolic stability was investigated in cell culture medium and human serum. Organ distribution and planar scintigraphy studies were performed in Balb/c nu/nu mice carrying subcutaneously transplanted SKRC 52 tumors. The results of our studies clearly identified amino acids that are important for target binding. Among various fragments and derivatives the ligand CaIX-P1-4-10 (NHVPLSPy) was found to possess increased binding potential in SKRC 52 cells, whereas no binding capacity for BxPC3 cells was observed. Binding of radiolabeled CaIX-P1-4-10 on CA IX positive cells could be inhibited by both the unlabeled and the native CaIX-P1 peptide but not by control peptides. Stability experiments indicated the degradation site in the sequence of CaIX-P1-4-10. Biodistribution studies showed a higher in vivo accumulation in the tumor than in most healthy tissues. CONCLUSIONS: Our data reveal modifications in the sequence of the CA IX affine ligand CaIX-P1 that might be favorable for improvement of target affinity and metabolic stability, which are necessary prior to the use of the ligand in clinical approaches.