Signaling through Raf-1 in the Neovasculature and Target Validation by Nanoparticles

A recent study demonstrated that vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) activate Raf-1 kinase in an experimental neovasculature system. The study showed that bFGF and VEGF activate p21-activated protein kinase-1 (PAK-1) and Src kinase, respectively. PAK-1 and Src kinases phosphorylate specific serine and tyrosine residues within the activation loop of Raf-1 kinase. Their findings further suggest that phosphorylation at these sites protects endothelial cells from apoptosis induced by both intrinsic and extrinsic factors. The tumor neovasculature provides specific molecular markers or "zip codes". This group of investigators has previously shown that nanosphere-aided targeting of the neovasculature with mutant Raf-1 causes regression of the tumor vasculature. Thus, nanoparticles coated with "zip code"-specific homing biomolecules may be useful for delivering anti-angiogenic molecules that can induce tumor regression.     

Teratocarcinosarcoma of the nose,paranasal sinuses and nasopharynx

Teratomas affecting the head and neck are rare tumours of ambiguous origin. The benign form is seen in children and mostly affects the nasopharynx. Malignant tumours in the upper jaw have been reported rarely. They are almost exclusively seen in the adult male. They are highly aggressive tumours that are difficult to diagnose pre-operatively due to the varied histological patterns. Treatment options available are surgery, radiotherapy or a combination of both. Despite intensive treatment, the prognosis is still poor. A rare case of teratocarcinosarcoma of the nose, paranasal sinuses and nasopharynx in a 25-year-old male is presented. The tumour had a non-germ cell tumour origin. The clinical features, pathologic characteristics and treatment are detailed. It was managed by surgery, radiotherapy and chemotherapy.     

Results of stapes surgery on patients with osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a heterogeneous group of connective tissue disorders. The classic triad of blue sclerae, spontaneous fractures and hearing loss is known as the Van der Hoeve and De Kleyn syndrome. Between 1989 and 2000, six patients with OI presented with conductive hearing loss. Five of them proceeded to stapedotomy. All the patients who had surgery had significant hearing gain. None of the patients had any complications. This study presents a higher incidence of spontaneous fractured crura as the cause of the conductive hearing loss than previously reported, and that the presence of a fractured crura with mobile footplate can be anticipated by the presence of a large conductive hearing loss. The pre- and postoperative results are presented and support the view that stapes surgery in OI can have encouraging results, provided the operator anticipates the possibility of a fractured crura and a mobile footplate.     

Patient eligibility for day case paediatric adenotonsillectomy

There is a growing trend towards day case surgery and departments are constantly under pressure from Health Trusts to perform more day case procedures. Adenoidectomy and tonsillectomy are being performed as day case procedures in many centres and literature has suggested that it is safe to do so, provided the population characteristics are favourable. A prospective study of 100 consecutive patients presenting to our department for tonsillectomy or adenotonsillectomy was undertaken to assess the eligibility of our patient group for day surgery. Medical and social history was obtained as per recommended guidelines. Only 27% of our patients were eligible for day surgery and only 17% of parents preferred the option of day case adenotonsillectomy. There is a marked difference between our group and those previously reported in the literature. This regional variation has implications in the safe expansion of day surgical procedures.     

Differential expression of carnosine, homocarnosine and N-acetyl-L-histidine hydrolytic activities in cultured rat macroglial cells

N-acetyl-L-histidine (NAH) and N-acetyl-L-aspartate (NAA) are representatives of two series of substances that are synthesized by neurons and other cells in the vertebrate central nervous system (CNS). Histidine containing homologs of NAH are β-alanyl-L-histidine or carnosine (Carn) and γ-aminobutyrl-L-histidine or homocarnosine (Hcarn). A homolog of NAA is N-acetylaspartylglutamate (NAAG). These substances belong to a unique group of osmolytes in that they are synthesized in cells that may not to be able to hydrolyze them, and are released in a regulated fashion to a second compartment where they can be rapidly hydrolyzed. In this investigation, the catabolic activities for NAH, Carn, and Hcarn in cultured macroglial cells and neurons have been measured, and the second compartment for NAH and Hcarn has been identified only with astrocytes. In addition, oligodendrocytes can only hydrolyze Carn, although Carn can also be hydrolyzed by astrocytes. Thus, astrocytes express hydrolytic activity against all three substrates, but oligodendrocytes can only act on Carn. The cellular separation of these hydrolytic enzyme activities, and the possible nature of the enzymes involved are discussed.     

Primary extracranial meningioma of the soft palate

Extracranial meningiomas comprise two per cent of all meningiomas. Primary extracranial meningiomas are even less common. The authors report the first case of a primary extracranial meningiomas of the soft palate, which presented as an intraoral mass. This was treated by surgical excision and there was no evidence of tumour recurrence at four years of follow-up.     

The role of fibreoptic laryngoscopy in infants with stridor

Stridor in infants may be potentially serious and would require further investigations in all cases. Laryngomalacia is the most common cause of congenital stridor. This is a self-limiting condition with a good prognosis but other causes of stridor should be excluded to enable the surgeon to plan further intervention if needed. Traditionally microlaryngoscopy and bronchoscopy under a general anaesthetic is performed to evaluate the airway. We have investigated the use of the flexible fibreoptic laryngoscope under local anaesthetics in infants with inspiratory stridor. The procedure was performed in the day surgery unit on a non-fasting, non-sedated child. A retrospective analysis of procedures performed between January 1998 and August 1999 was carried out. Of the 43 patients studied, laryngomalacia was diagnosed in 35, vocal cord palsies in six and two infants had a normal larynx. There were no complications during the procedure and only one child required further intervention. The results showed that the combination of fibreoptic laryngoscopy under local anaesthetic with follow-up is a safe, effective and cost effective method of assessing stridor in this group of patients.     

Laryngoceles - presentations and management

Introduction  Laryngoceles usually present as cervical masses with or without hoarseness of voice. They are mostly unilateral and may be symptomatic or asymptomatic. They are classified as internal, external or combined. They have been described to be an occupational hazard among wind instrument players or glass blowers. They also occur in association with neoplasms of the larynx. Materials and methods  Here we report five patients with laryngoceles of whom two had bilateral laryngoceles, which are very rare. One patient had associated laryngeal malignancy for which total laryngectomy was performed. Two cases underwent excision via cervical approach. The rest were managed conservatively. Conclusion  Symptomatic cases have to be managed surgically while asymptomatic ones may be managed conservatively.     

Muco-adhesive multivesicular liposomes as an effective carrier for transmucosal insulin delivery

Considering limitations of conventional insulin therapies, the present study characterizes usefulness of novel mucoadhesive multivesicular liposomes as a mucoadhesive sustained release carrier of insulin via nasal and ocular routes, thus attempts to develop non-invasive carrier system for the controlled release of bioactives. Multivesicular liposomes (MVLs) of 26-34 microm were prepared with a high protein loading (58-62%) and were coated with chitosan and carbopol. These mucoadhesive carriers were characterized by zeta potential studies, in vitro mucoadhesion test and insulin protective ability against nasal aminopeptidase. In vitro, mucoadhesive carriers released insulin for a period of 7-9 days compared to 24 h of conventional liposomes. After intranasal administration to STZ induced diabetic rats, the mucoadhesive MVLs (chitosan coated MVLs) effectively reduced plasma glucose level up to 2 days (35% reduction), compared to non-coated MVLs (32% at 12 h) and conventional liposomes (34% at 8 h). Although the differences are statistically insignificant, chitosan coated formulation has shown a better hypoglycemic profile as the effects were prolonged compared to carbopol coated formulation. When compared to ocular route, chitosan formulation after nasal administration has shown better therapeutic profile as the hypoglycemic effects were prolonged until 72 h. The effectiveness of this chitosan coated MVLs was further demonstrated by the significant quantities of ELISA detectable insulin levels after nasal (334.6 microIu/ml) and ocular (186.3 microIu/ml) administration. These results demonstrate that mucoadhesive carrier is a viable option for a sustained release transmucosal insulin carrier, and open an avenue to develop a non-invasive carrier platform for the controlled release of bioactives.     

Combined Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Outcome After Liver Transplantation

Background  

Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma is a rare hepatobiliary malignancy incorporating components derived from both hepatocyte and intrahepatic bile duct epithelium. The natural history, treatment, and prognosis of this distinct cancer differ from hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) and are not completely understood. There is considerable controversy about the classification, treatment, and survival, which in turn is related to the rarity of the condition. Treatment options include surgical resection and the prognosis is believed to be better than CC but worse than HCC alone.