Molecular interactions in juvenile nasopharyngeal angiofibroma: preliminary signature and relevant review.

BACKGROUND: The molecular profile of juvenile nasopharyngeal angiofibroma (JNA) is extremely variable. In absence of established molecular signature the molecular targeting seems difficult for this heterogeneous disease. To establish a basic molecular signature, this paper analyses the interaction of 7 markers according to their ranks as per the decreasing scale of molecular expression. MATERIALS AND METHODS: Fourteen samples of JNA were obtained following surgical excision and mRNA expressions were established through real-time polymerase chain reaction (RT-PCR) for vasculoendothelial growth factor (VEGF), fibroblastic growth factor (FGF), c-Kit, c-myc, Ras, platelet-derived growth factor (PDGF) and tumor suppressor gene p53. Nasal polyp was taken as control. The quantitative expressions for every marker were ranked on a decreasing scale and were compared by Spearman's rank correlation test to define the statistically significant interaction. An attempt was also made to overview the basic clinical parameters (age, duration of symptoms, radiological staging, intraoperative haemorrhage and tumor-volume/weight) associated with enhanced molecular expressions for every marker. RESULTS: Five significant molecular interactions were identified on the basis of rank-correlation: (1) FGF/VEGF (p < 0.01); (2) Ras/FGF (p < 0.01); (3) Ras/VEGF (p < 0.001), (4) FGF/c-Kit (p < 0.05); (5) c-Myc/p53 (p < 0.05). These basic 'molecular signatures' suggested a preliminary 'molecular classification'. The implication of the interactions between FGF, VEGF and Ras were the most outstanding observation that not only revealed a direct relationship but were also consistent with the clinical behaviour. In addition, a non-significant interaction was identified with c-Myc/PDGF and also an inverse relationship between FGF/c-Kit. CONCLUSIONS: FGF, VEGF, and Ras being significantly interrelated seemed to be the 'most soft' molecular targets for JNA. The other targets observed included FGF/c-Kit and c-Myc/p53 interactions that seemed equally important but only after VEGF/FGF/Ras complex per se. These preliminary signatures are likely to provide a background for further expansion of the molecular classification of JNA.

Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma.

BACKGROUND: Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. METHODS: Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. RESULTS: Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. CONCLUSION: Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

Prevalence of otitis media in school going children in Eastern Nepal.

OBJECTIVES: To find out the prevalence of otitis media in school going children from lower socio-economic strata. MATERIAL AND METHODS: This study was carried out in a government school, Shree Naragram Secondary School in Morang district, eastern Nepal, and included 1050 children aged between 5-15 years. RESULTS: Of the 1050 school children, 346 children were found to have various ENT related problems. Hearing assessment revealed a conductive hearing loss on one or both sides in 114 cases (87%). Various middle ear pathologies were detected in these children, out of which chronic suppurative otitis media "Tubotympanic type" was the most common, followed by otitis media with effusion. The prevalence of otitis media in these children was found to be13.2% and those with hearing loss comprised 12.47%. Prevalence of otitis media is found to be much higher in school going children as compared to adults, and is even higher amongst children belonging to the lower socio-economic strata. Conditions complicating otitis media are more common and severe in children as compared to adults. CONCLUSION: Primary ear care education to teachers, students and guardians can prevent these vulnerable children from developing hearing impairment. School based study could be one of the useful and cost-effective modality aimed at community oriented program.

Changing trends in the incidence of juvenile nasopharyngeal angiofibroma: seven decades of experience at King George's Medical University, Lucknow, India.

BACKGROUND: The occurrence of juvenile nasopharyngeal angiofibroma is reportedly higher in India than in some other parts of the world, and our centre has seen a four-fold increase in its occurrence across seven decades. METHODS: This paper reports a retrospective archival analysis of 701 juvenile nasopharyngeal angiofibroma cases from 1958 to 2013, and considers probable environmental factors in an Indian context that may affect its biology and the global distribution, as reported in the literature. RESULTS: A continuously progressive increase in occurrence was evident, but the rapid rise observed in the current decade was alarming. The world map of juvenile nasopharyngeal angiofibroma incidence does not reflect true global distribution given the paucity of reporting. Our centre has dealt with approximately 400 cases in the last 24 years. CONCLUSION: With the alarming increase in juvenile nasopharyngeal angiofibroma incidence, there is a need for a registry to define its epidemiology. The world literature needs to reflect the status of juvenile nasopharyngeal angiofibroma incidence in the third world as well. Environmental factors known for hormone disruptive actions may influence its occurrence. Such aspects need to be considered to plan specific prevention policies.

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

OBJECTIVE: A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. METHOD: A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. RESULTS: Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. CONCLUSION: Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

In defence of transpalatal, transpalatal-circumaxillary (transpterygopalatine) and transpalatal-circumaxillary-sublabial approaches to lateral extensions of juvenile nasopharyngeal angiofibroma.

BACKGROUND: Juvenile nasopharyngeal angiofibroma often presents with lateral extensions. In countries with limited resources, selection of a cost-effective and least morbid surgical approach for complete excision is challenging. METHODS: Sixty-three patients with juvenile nasopharyngeal angiofibroma, with lateral extensions, underwent transpalatal, transpalatal-circumaxillary (transpterygopalatine) or transpalatal-circumaxillary-sublabial approaches for resection. Clinico-radiological characteristics, tumour volume and intra-operative bleeding were recorded. RESULTS: The transpalatal approach was suitable for extensions involving medial part of pterygopalatine fossa; transpalatal-circumaxillary for extensions involving complete pterygopalatine fossa, with or without partial infratemporal fossa; and transpalatal-circumaxillary-sublabial for extensions involving complete infratemporal fossa, even cheek or temporal fossa up to zygomatic arch. Haemorrhage was greatest with the transpalatal-circumaxillary-sublabial approach, followed by transpalatal approach and transpalatal-circumaxillary approach (1212, 950 and 777 ml respectively). Tumour size (volume) was greatest with the transpalatal-circumaxillary approach, followed by transpalatal-circumaxillary-sublabial approach and transpalatal approach (40, 34 and 29 mm3). There was recurrence in three cases and residual disease in two cases. Long-term morbidity included small palatal perforation (n = 1), trismus (n = 1) and atrophic rhinitis (n = 2). CONCLUSION: These modified techniques, performed with endoscopic assistance under hypotensive anaesthesia, without embolisation, offer a superior option over other open procedures with regard to morbidity and recurrences.

Time dependent immunomodulatory response of exogenous melatonin to killed Pasteurella multocida (P52 strain) vaccine in albino rats.

The effect of time of administration of exogenous melatonin (M) at the rate of 100 microg/Kg BW of rat/day for 14 days on immunomodulation to killed Pasteurella multocida (P52 strain) vaccine (KPMV) was investigated in male albino rats during spring season with photoperiod of LL 13: DD 11 h and 25 +/- 2.5 degrees C air temperature and 70 +/- 4% relative humidity. The experiment was conducted at an altitude of 172 mts above mean sea level at latitude 28.20 degrees north, longitude 79.24 degrees east (Bareilly, U.P. India). The experimental animals were divided in-groups of 8 rats each, as KPMV + M at 4.00 h; KPMV + M at 16.00 h; KPMV and their controls M4, M16, PBS respectively. Humoral immune response was monitored at weekly intervals by an indirect ELISA and cellular immunity by leukocyte migration inhibition test (LMIT) and delayed type of hypersensitivity (DTH). As evinced by in-vitro assays and in-vivo protection studies, both humoral and cellular immune responses to KPMV were augmented in rats receiving exogenous melatonin at 4.00 h as compared to slightly reduced responses in rats treated with melatonin at 16.00 h. It was concluded that the circadian timings of melatonin administration modulate immune response in rats.

Cost-effective diagnostic nasal endoscopy with a modified otoscope.

We present 'Mishra's rhinoscope', a novel, cost-effective technique of zero-degree rigid nasoendoscopy with a modified otoscope, the results of which are comparable with the fibreoptic sinoscope. This is particularly suited for the developing world where financial constraints restrict the diagnosis of an occult nasal pathology.

Angiofibromas of the postnasal space: a critical appraisal of various therapeutic modalities.

Angiofibromas of the postnasal space are an enigma to the treating surgeon in view of their extensions around the skull base. The availability of modern investigative procedures has to some extent facilitated the decision making process in choosing a suitable surgical approach. Proper tumour staging and the earliest and widest possible exposure tailored to the needs of the specific situation together with adequate blood replacement is the key to success in minimizing the chances of the recurrence. The present study aims at an evaluation of the methodology adopted in 100 serial cases of angiofibromas of the postnasal space. After initial surgery, a further 31 procedures were needed for the management of recurrences.

A rational classification of angiofibromas of the post nasal space.

Angiofibromas of the post nasal space have the potential to extend in all directions along predetermined pathways with a definite mode and chronological pattern. In order to understand their clinical behaviour, methods of treatment and prognosis, a system of clinical staging based on conventional and tomographic observations has been found useful in this series of cases. The classification has been evolved according to the extent of the tumour involvement but also the age of onset, duration, size and area of encroachment including the surgical approach and consequent prognosis. Deficiencies in the earlier classifications are discussed.

Unusual solitary osteochondroma of the mandibular ramus.

Mandibular osteochondromas, although rare, predominantly involve the condyloid and coronoid processes. An extremely rare case arising from the inner aspect of the gonion is reported here. Only one such case has been reported in the literature so far. Despite being very slow growing and having a benign course, histopathological examination showed reactive changes that may be confused with sarcomatous transformation. We advocate surgical excision using a combined external and internal approach followed by regular post-operative review. The relevant literature has been reviewed but various surgical approaches as advocated in the past have not been found suitable.

An enzyme linked immunoassay for estimation of antibodies to Newcastle disease virus strains.

The sensitivity of enzyme linked immunoassay (ELISA) was compared to that of haemagglutination inhibition (HI) test in detection of humoral antibodies in birds vaccinated with Newcastle disease virus (NDV). The highest antibody titre at day 21 post-vaccination as detected by ELISA in the sera of vaccinated birds was 2560 by all strains in contrast to the HI titres of 640 to 1280. The antibody titre was higher in all pre- and post-vaccination sera as determined by ELISA than detected by HI test.

Tetanus with local palsy.

Five cases of tetanus with local palsy are reported. They presented with palatal palsy, pseudohernia, paralysis of both lower limbs, 3rd and 7th cranial nerve palsies and only 7th nerve palsy. Except the last tetanus became generalised in all.

Bacteriological profile in chronic suppurative otitis media in Eastern Nepal.

Aural swabs were collected from 250 patients with chronic suppurative otitis media (CSOM) (tubotympanic disease). Duration of ear discharge was more than 6 months for culture and sensitivity test. The disease was unilateral in 178 (71.2%) and bilateral in 72 (28.8%) patients. From a total of 322 aural swab cultures, 324 organisms were isolated with predominance of Pseudomonas aerugimosa (36.4%) followed by Staphylococcus aureus (30.2%). All the isolated Gram-negative organisms showed in vitro sensitivity to ciprofloxacin, amikacin, ofloxacin, and gentamycin whereas cloxacillin, ofloxacin, erythromycin, ciprofloxacin, gentamicin and tetracycline were more effective against Gram-positive isolates. Most isolates were resistant to amoxycillin. It is concluded that ciprofloxacin is preferred to aminoglycosides as an important tool in the treatment of CSOM because of its lower cost, lack of ototoxicity and availability as topical oral preparations.

Comparative status of oxidative damage and antioxidant enzymes in chronic tonsillitis patients.

Comparative study of two modalities i.e. antioxidant therapy (by vitamin E) and tonsillectomy was done in chronic tonsillitis patients, the study included 80 cases. It was found that both modalities were affective than tonsillectomy. Thus the use of antioxidant may be a promising alternative for the tonsillectomy.

A study of free radicals and scavenging enzyme in tonsillitis.

The present study is a comparison of malonaldialdehyde (MDA) level and superoxide dismutase (SOD) activity between controls and in tonsillitis patients of different degree before (pre) and after (post) surgery (tonsillectomy). The SOD activity increases in pretonsillectomy cases according to severity of disease and there is a rise in MDA level whereas after tonsillectomy although the increase in SOD is marginal but MDA declines sharply as compared to pretonsillectomy patients indicating that the SOD exerts its protective effect after surgery.