Ehlers-Danlos syndrome – vascular type (ecchymotic variant): cutaneous and dermatopathologic features

Ehlers-Danlos syndrome – vascular type, the only lethal form, is rarely reported in dermatology literature. It is characterized by translucent, atrophic skin, easy bruising, arterial, intestinal and/or uterine fragility manifesting as varicose veins, aneurysms and vascular/visceral/uterine rupture. As its dermatopathologic features are not well elucidated, diagnosis is often made after a catastrophic complication or at autopsy. This 36 year-old non-consanguineous male had brown-black plaques with atrophy and frequent ulceration over legs and dorsal feet and tortuous varicose veins around ankles for the past 15 years. Perivenous skin was translucent and hypopigmented. He had multiple and ecchymotic keloids and small atrophic, pityriasis versicolor-like lesions over trunk. He did not have hypermobile/hyperextensible skin and joints and showed no systemic or investigative abnormality. Histopathologic features of atrophic lesion included blood extravasation in atrophic epidermis/dermis, focal clustering and dilatation of blood vessels, malformed vessel walls, abundant hemosiderin in the dermis and homogenously stained/whorled patterned collagen especially around blood vessels. Pathology of keloidal lesion showed new collagen and vascular fragility. These histopathologic features appear of diagnostic value especially in patients who have compatible clinical findings but cannot afford confirmation by biochemical testing for abnormal synthesis of type III procollagen or identification of mutations in the COL3A1 gene.     

Myxopapillary ependymoma of lumbosacral region with metastasis to both cerebellopontine angles: report of a rare case

Introduction Myxopapillary ependymomas are low grade tumours that are known to recur locally even after complete excision, but metastasis to distant sites is extremely uncommon. Case report We report an unusual case of lumbo-sacral myxopapillary ependymoma in a 13-year-old boy with metastasis to both cerebellopontine angles. To the best of our knowledge, this is the youngest patient of metastatic myxopapillary ependymoma.     

ORL-HNS training in South Africa

An out line of the scheme of training specialists in Otorhinolaryngology-Head and Neck Surgery (ORL-HNS) in South Africa is given and the difference with Indian training discussed     

Regulation of immunoglobulin heavy-chain gene rearrangements

Summary: Regulated assembly of antigen receptor gene segments to produce functional genes is a hallmark of B‐ and T‐lymphocyte development. The immunoglobulin heavy‐chain (IgH) and T‐cell receptor β‐chain genes rearrange first in B and T lineages, respectively. Both loci require two recombination events to assemble functional genes; D‐to‐J recombination occurs first followed by V‐to‐DJ recombination. Despite similarities in overall rearrangement patterns, each locus has unique regulatory features. Here, we review the characteristics of IgH gene rearrangements such as developmental timing, deletion versus inversion, D_H gene segment utilization, ordered recombination of V_H gene segments, and feedback inhibition of rearrangement in pre‐B cells. We summarize chromatin structural features of the locus before and during recombination and, wherever possible, incorporate these into working hypotheses for understanding regulation of IgH gene recombination. The picture emerges that the IgH locus is activated in discrete, independently regulated domains. A domain encompassing D_H and J_H gene segments is activated first, within which recombination is initiated. V_H genes are activated subsequently and, in part, by interleukin‐7. These observations lead to a model for feedback inhibition of IgH rearrangements.     

Conservative management of a major post-intubation tracheal injury and review of current management

Tracheal rupture represents a rare but serious complication of intubation. We discuss a case of a major post-intubation rupture. After investigation with CT scan tracheoscopy and bronchoscopy a low tracheostomy was formed protecting the rupture from pressure changes associated with ventilation. The patient was managed with minimal surgical intervention, low tracheostomy with antibiotic cover and monitoring in the intensive care unit for 24 h before being woken and moved to a ward after 48 h. The patient made a full and uncomplicated recovery and was discharged 2 weeks after the original injury. Most of the literature on the subject is made up of review of case reports that conclude management of such a major tear must be with surgical repair. This however confers significant morbidity and an associated high mortality. We suggest an alternative management protocol.     

Characterization of solid-state forms of celecoxib.

This study deals with the generation and characterization of various solid-state forms of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. The drug was subjected to polymorphic screen using different solvents to explore the possibility of existence of different solid forms. N,N-Dimethyl acetamide (DMA) and N,N-dimethyl formamide (DMF) yielded solvates in 1:1 stoichiometric ratio. Quench cooling of the melt resulted in amorphous form of the drug. All these solid-state forms were characterized by thermoanalytical (DSC, TGA, HSM), crystallographic (XRD), microscopic (polarized, SEM), spectroscopic (FTIR), and elemental analysis techniques. Solubility and van't Hoff studies were carried out for their thermodynamic interpretation. Influence of morphology of different solid-state forms on flow behavior was also investigated. Molecular modeling studies were used to elucidate the interaction between solute and solvent molecules in the solvate.     

Recent advances in understanding the pathogenesis of polyglutamine diseases: involvement of molecular chaperones and ubiquitin-proteasome pathway

Polyglutamine diseases consist of a group of familial neurodegenerative disorders caused by expression of proteins containing expanded polyglutamine stretch. Over the past several years, tremendous progress has been made in identifying the molecular mechanisms by which the expanded polyglutamine tract leads to neuronal dysfunction and neurodegeneration. A common feature of most polyglutamine disorders is the occurrence of ubiquitin-positive neuronal intranuclear inclusions. The appearance of ubiquitinated aggregates implies an underline incapability of the cellular chaperones and proteasome machinery that normally functions to prevent the accumulation of misfolded proteins. Here we review the recent studies that have revealed a critical role for molecular chaperones and ubiquitin-proteasome pathway in the pathogenesis of polyglutamine diseases.     

Influence of lamella features of UHMWPE on its physical and uniaxial tensile properties. I. Effect of sterilization method in uncrosslinked and unaged materials

The changes in the tensile toughness (U), degree of crystallinity (%C), melting temperature (Tm), lamella thickness, and lamella alignment of uncrosslinked and unaged GUR 1150HP ultra-high-molecular-weight polyethylene specimens, following different sterilization treatments (none, gamma-irradiation in air, gamma-irradiation in a nitrogen-rich atmosphere, ethylene oxide gas, and gas plasma) were determined. For each of the properties - U, %C, and Tm - the only significant difference in the mean value was found between the set of specimens gamma-irradiated in air, on the one hand, and each of the other sets, on the other hand. It was found that lamella thickness showed little change between the groups of specimens but there was a significant difference in the lamella orientation between the set of specimens that had been gamma-irradiated in air, on the one hand, and each of the other sets, on the other. It thus appears that the changes seen in the physical and mechanical properties determined may be a reflection of the change in the polymer's lamella alignment.     

Geographic contiguity and genetic affinity among five ethnic populations of Manipur,India: further molecular studies based on VNTR and STR loci

BACKGROUND: Apart from traditional markers studied among a few numerically small, geographically defined surveys among Mongoloid populations in northeastern parts of India, very little is known about their genomic diversity at the molecular level. PRIMARY OBJECTIVE: This study seeks to investigate how best the variable number tandem repeat (VNTR) and short tandem repeat (STR) loci together can detect the patterns of the genetic affinity among five geographically contiguous, linguistically and socio-culturally diverse Mongoloid-affiliated populations of Manipur in northeastern regions of India. SUBJECT AND METHODS: Blood samples were collected from unrelated and randomly selected volunteers of five ethnic populations (Meitei, Kuki, Naga, Hmar and Manipuri Muslim) from different parts of the state. Allelic variation in four minisatellite loci (D1S7, D4S139, D5S110 and D17S79) and three STR loci (vWA, FESFPS and F13AO1) was studied. RESULTS: Average heterozygosity values among the five groups for the minisatellite range from 68% to 94%, while the hypervariable three STR loci were between 60% and 88%. In the populations, all the studied loci were highly polymorphic, with almost no departure from Hardy-Weinberg equilibrium. The gene differentiation for the VNTR loci was lower and moderate (G(st) = 0.030) in comparison with microsatellites (G(st) = 0.043). The neighbour-joining method of clustering based on both type of molecular markers reveals a close cluster for the tribal groups of Kuki, Naga and Hmar, while Manipur Muslim stand distinct in both the trees. The clustering pattern obtained from the combined DNA marker loci matches more closely the pattern from STR loci than that obtained from VNTR loci. CONCLUSIONS: The results reinforce that using both VNTR and STR loci in detecting regional genetic affinity among the populations is more effective than using VNTR or STR independently, and also confirm the results obtained from the serological and electrophoretic data. However, the clustering pattern obtained from combined DNA markers is more in conformity with the pattern obtained by STR loci rather than with VNTR loci. Despite linguistic, geographical and cultural barriers, the populations show genetic affinity among the four populations except in the case of the migrant Manipur Muslim group.