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.     

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     

Probiotic lactobacilli: an innovative tool to correct the malabsorption syndrome of vegetarians?

Vegetarians may have subtle nutritional deficiencies which have been related to the occurrence of an unrecognized malabsorption syndrome. The excess phytate content in cereals, nuts, legumes and oilseeds which represent the mainstay of their food intake, seems to play a central role in the pathogenesis of this malabsorption syndrome as an inverse relationship has been shown to link the phytate content of the diet with the intestinal absorption of trace minerals and proteins. We postulate that manipulating the endogenous digestive microflora of subjects on a vegetarian diet through administering probiotic lactic bacteria would represent an innovative tool to counteract the occurrence of the malabsorption syndrome dependent on the high phytate content of their diet. Even though there are no data about the composition of endogenous digestive microflora in subjects on a vegetarian diet, we expect that probiotic lactobacilli can interact with or affect distinct yet interrelated components within the intestinal milieu, such as epithelial cells, enteric flora, and/or mucosal immune cells. This would ultimately translate into the correction of the unregulated mechanisms implicated in the altered intestinal absorption of trace metals and proteins commonly seen in vegetarians. Clinical experience with probiotic therapy of patients with inflammatory bowel disease fully agrees with this view. One additional point of interest is that probiotic lactobacilli, and other species of the endogenous digestive microflora as well, are an important source of the enzyme phytase which catalyses the release of phosphate from phytate and hydrolyses the complexes formed by phytate and metal ions or other cations, rendering them more soluble ultimately improving and facilitating their intestinal absorption. The regular intake of probiotic preparation, may represent a cheap and safe tool in order to convert a diet with a low potential for bioavailability of trace minerals and proteins, such as the vegetarian diet, into a diet with a high bioavailability potential. The benefit of such an approach would not be restricted to vegetarians.     

Allele sharing at six VNTR loci and genetic distances among three ethnically defined human populations

Because of their high degree of polymorphisms, the variable number of tandem repeat (VNTR) loci have become extremely useful in studies involving gene mapping, determination of identity and relatedness of individuals, and evolutionary relationships among populations. However, there are some concerns regarding whether or not the patterns of such genetic variation can be studied by the classical population models that are developed for studying genetic variation at blood groups and protein loci, since VNTR alleles detected by molecular size may not always be identical by descent. Although theoretical and empirical studies demonstrate that this concern is overstated, this study provides further support of the application of the traditional mutation-drift models to predict the pattern of intra- and inter-populational variation at VNTR loci. By comparing genetic variation at six VNTR loci with that at 16 blood groups and protein loci in three ethnically defined populations, we show that the patterns of variability at these two sets of loci are in general parallel to each other. Shared VNTR alleles among populations are generally more frequent than the ones which are not present in every population; the proportion of shared alleles among populations increases with increasing genetic similarity of populations; and the number of VNTR alleles is positively correlated with gene diversity at these loci. All of these observations are in agreement with the prediction of the mutation-drift models, particularly when the possibility of forward-backward mutations are taken into account. This parallelism of genetic variation at VNTR loci and blood groups/protein loci further asserts the potential of using such hypervariable loci for microevoltionary studies, where closely related populations may exhibit considerably less allele frequency differences at the classical blood group and protein loci. © 1992 Wiley-Liss, Inc.     

Processing of interaural temporal disparities in the medial division of the ventral nucleus of the lateral lemniscus

The medial division of the ventral nucleus of the lateral lemniscus (VNLLm) contains a specialized population of neurons that is sensitive to interaural temporal disparities (ITDs), a potent cue for sound localization along the azimuth. Unlike many ITD-sensitive neurons elsewhere in the auditory system, neurons in the VNLLm respond only at the onset of tones. An onset response may be significant for behavior because, under echoic conditions, tones require sharp onsets for accurate localization. In contrast, noise can generally be localized even with gradual onsets, presumably because transients occur at random intervals in noise. We recorded responses of neurons in the VNLLm to tones and noise in unanesthetized rabbits. We found that although tones elicited a transient response, noise elicited a sustained response as if it was a sequence of transients. The responses to tones indicate that these neurons represent a secondary stage in the processing of ITDs. The onset response to tones was only weakly synchronized to the phase of the tone, indicating that neurons in the VNLLm inherit their sensitivity to ITDs from their inputs. The latencies were short (~8 ms), implying that the ITD sensitivity is derived from ascending inputs. Most neurons in the VNLLm discharged maximally at the same ITD at all frequencies, a characteristic shared with neurons of the medial superior olive. However, the latency of neurons in the VNLLm to interaurally delayed stimuli is linked strongly to the timing of the contralateral stimulus. This suggests that these neurons receive a suprathreshold, contralateral input that is modulated by a subthreshold input conveying information about ITDs. Other stations in the auditory pathway contain a subset of neurons that respond transiently to tones and are sensitive to ITDs. These neurons may represent a novel pathway that assists in localizing sounds in the presence of reflections.     

Safety and feasibility of single-incision laparoscopic totally extraperitoneal inguinal hernia repair: a retrospective comparative analysis of 163 patients

European Surgery - To analyze the benefit and feasibility of single-incisional laparoscopic totally extraperitoneal (SIL TEP) repair compared with those of conventional laparoscopic TEP...     

Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivit to TNF-{alpha}-mediated cell death

The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharideon the sensitivity to tumor necrosis factor (TNF)--medlatedcell death was studied In an In vitro system. Since secretionof TNF- Is a part of the early host response to viral and bacterialinfection, we examined whether mimicking the Infection withviral and bacterial products could affect the response of cellsto TNF-. Incubation of WEHI 164 fibrosarcoma cells with dsRNAor lipopolysaccharide (LPS) significantly increased their sensitivityto TNF--mediated lysis and to TNF-secreting inflammatory T cell-mediatedlysis. Thus, these products could induce Increased sensitivityto TNF- In cells In an inflammatory focus, possibly contributingto selective elimination of Infected but not healthy cells bythis non-specific cytokine. Additionally, our data show thatboth dsRNA and LPS, as well as TNF- Itself, rapidly Induce nuclearfactor-xB (NF-*B), a DNA-bindlng protein Implicated In regulationof gene expression. We suggest that NF-xB could regulate genescrucial for the induction of cell death by TNF-.     

Antibody and memory B cell responses to the dengue virus NS1 antigen in individuals with varying severity of past infection

To further understand the role of NS1-specific antibodies (Abs) in disease pathogenesis, we compared neutralizing antibody levels (Nabs), NS1-Ab levels, IgG antibody subclass profiles and NS1-specific memory B-cell responses (Bmems) in individuals, with varying severity of past dengue. Nabs (Neut50 titres) were assessed using the Foci Reduction Neutralization Test (FRNT) and in-house ELISAs were used to assess NS1-Abs and NS1-Ab subclasses for all four DENV serotypes in individuals with past DF (n = 22), those with past DHF (n = 14) and seronegative (SN) individuals (n = 7). B-cell ELISpot assays were used to assess NS1-specific Bmem responses. 15/22 (68.18%) individuals with past DF and 9/14 (64.29%) individuals with past DHF had heterotypic infections. Neut50 titres were found to be significantly higher for DENV1 than DENV2 (p = 0.0006) and DENV4 (p = 0.0127), in those with past DHF, whereas there was no significant difference seen in titres for different DENV serotypes in those with past DF. Overall NS1-Ab to all serotypes and NS1-specific IgG1 responses for DENV1, 2 and 4 serotypes were significantly higher in those with past DHF than individuals with past DF. Those with past DHF also had higher IgG1 than IgG3 for DENV1 and DENV3, whereas no differences were seen in those with past DF. Over 50% of those with past DF or DHF had NS1-specific Bmem responses to >2 DENV serotypes. There was no difference in the frequency of Bmem responses to any of the DENV serotypes between individuals with past DF and DHF. Although the frequency of Bmem responses to DENV1 correlated with DENV1-specific NS1-Abs levels (Spearman r = 0.35, p = 0.02), there was no correlation with other DENV serotypes. We found that those with past DF had broadly cross-reactive Nabs, while those with past DHF had higher NS1-Ab responses possibly with a different functionality profile than those with past DF. Therefore, it would be important to further evaluate the functionality of NS1-specific antibody and Bmem responses to find out the type of antibody repertoire that is associated with protection against severe disease.     

Adenoid Cystic Carcinoma of the Salivary Glands: A Review of 10 Years

A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.