Cartilage Palisades in Type 3 Tympanoplasty: Functional and Hearing Results

To evaluate the functional and hearing outcomes using full thickness broad cartilage palisades for tympanic membrane reconstruction in type 3 tympanoplasty with titanium prostheses. The retrospective study performed at a tertiary referral institute included 30 patients with posterior mesotympanic retraction pockets or tympanic membrane perforations requiring tympanic membrane and type 3 ossicular reconstruction. Patients with disease extending beyond the aditus requiring canal wall down mastoidectomy were excluded. Disease removal from posterior mesotympanic and epitympanic recesses was confirmed using angled endoscopy and ossicular reconstruction was performed using titanium partial or total ossicular replacement prostheses. Tympanic membrane reconstruction was done, with or without attic reconstruction, using full thickness broad cartilage palisades harvested from the tragus with perichondrium attached laterally. Patients were assessed at 24 and 48 weeks for graft status and any evidence of implant extrusion. Hearing evaluation was done using subjective assessment and pure tone audiometry. In total, 27 out of 30 patients had intact and completely healed grafts at 48 weeks postoperatively (a success rate of 90 %) showing full union and epithelialization of palisades, and with three patients displaying small defects. The mean pure tone air bone gap pre- and postoperatively was 32.4 and 8.8 dB, respectively, with most patients reporting satisfactory postoperative hearing. No evidence of implant extrusion was found in the 48-week period. Tympanic membrane reconstruction using full thickness palisades of tragal cartilage provides good functional and hearing outcomes in type 3 tympanoplasty with titanium prostheses.     

CORONARY RISK ANALYSIS - A STITCH IN TIME

Coronary heart disease (CHD) is the major cause of sudden death amongst adults throughout the globe. Though the prevalence of CHD is increasing steadily all over, CHD amongst Indians is peculiar in the sense that it is more prevalent, more severe and appears at younger age. Development of CHD depends upon the status of various coronary risk factors in one''s body. It has been observed that to measure the impact of risk factors for the cardiac health of a person, collective impact of all the known risk factors taken together should be calculated rather than individual risk factors. DEBEL (Defence Bio-Engineering and Electro-Medical Laboratory) is developing a cardiac risk analyser to calculate the absolute coronary risk of an individual in next 2,5 or 10 years and help in managing his coronary risk status.KEY WORDS: Absolute coronary risk, Coronary heart disease, Coronary risk factors     

Extensive nasopharyngeal angiofibromas: the maxillary swing approach

The objective of this study was to evaluate the efficacy and outcome using the maxillary swing approach for the management of extensive nasopharyngeal angiofibromas. A retrospective analysis in a tertiary care center revealed five cases with extensive nasal angiofibromas operated using the maxillary swing approach between 2010 and 2012. All patients had tumor extension to the lateral-most portions of the infratemporal fossa with complete occupation and destruction of the lateral wall of the sphenoid sinus causing abutment to the cavernous sinus and complete involvement of the pterygopalatine fossa and pterygoid base. One patient displayed full occupancy of the maxillary sinus as a consequence of erosion of the posterior and medial walls of the maxillary sinus, while another had severe temporal lobe compression through the roof of the infratemporal fossa. All patients underwent tumor excision using the maxillary swing approach. Patients were followed up for a minimum period of 1 year after surgery. The maxillary swing approach gave optimal exposure of the entire central skull base including the infratemporal fossa and its extreme lateral and superior aspects. Adequate tumor exposure and vascular control could be achieved in all cases resulting in complete tumor excision. The mean operative time was 4.5 h. Post-operative healing was satisfactory with palatal fistula formation in two cases and all patients remaining disease-free up to the present time. One had minimal misalignment of the halves of the upper jaw and two had epiphora, of which one required dacryocystorhinostomy. The maxillary swing is an effective approach in the management of extensive nasopharyngeal angiofibromas and leads to optimal anatomical exposure with minimal morbidity.     

Integral Role of PTP1B in Adiponectin-Mediated Inhibition of Oncogenic Actions of Leptin in Breast Carcinogenesis

The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a “guardian angel adipocytokine” for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK) and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B), which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast carcinoma in obese patients with high leptin levels.     

Novel exon 2 α spectrin mutation and intragenic crossover: three morphological phenotypes associated with four distinct α spectrin defects

Hereditary pyropoikilocytosis is a severe hemolytic anemia caused by spectrin deficiency and defective spectrin dimer self-association, typically found in African populations. We describe two Utah families of northern European ancestry including 2 propositi with atypical non-microcytic hereditary pyropoikilocytosis, 7 hereditary elliptocytosis members and one asymptomatic carrier. The underlying molecular defect is a novel mutation in the alpha(α) spectrin gene, SPTA^R34P that impairs spectrin tetramer formation. It is inherited in trans to the hypomorphic SPTA^αLELY in the 2 propositi and 5 of 7 hereditary elliptocytosis individuals indicating that SPTA^αLELY is not the sole determinant of the variable clinical expression. α Spectrin mRNA was mildly decreased in all hereditary elliptocytosis subjects, whereas both hereditary pyropoikilocytosis propositi had a severe decrease to ~10% of normal. Genotyping identified a unique SPTA intragenic crossover and uniparental disomy in one hereditary elliptocytosis individual. Two additional crossover events demonstrated the susceptibility of SPTA gene to rearrangement and revealed a novel segregation of the two SPTA^αLELY mutations. We conclude that the profound phenotypic heterogeneity in these families can be attributed to the SPTA^R34P mutation in combination with: 1) inheritance in trans of either SPTA^αLELY; or 2) the wild-type SPTA; 3) a decrease of α spectrin mRNA; and 4) SPTA intragenic crossover.