Toxic epidermal necrolysis; 15 years'' experience in a Dutch burns centre

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe and potentially fatal drug reaction characterized by an extensive skin rash with blisters and exfoliation, frequently accompanied by mucositis. The wounds caused by TEN are similar to second-degree burns and severe cases may involve large areas of skin loss. OBJECTIVES: Analysis of our results in patients with TEN and evaluation of the variety of therapeutic interventions that has been studied and suggested in TEN. PATIENTS/METHODS: Retrospective analysis of 19 consecutive patients with TEN treated in our burns centre between 1989 and 2004. RESULTS: Immediate withdrawal of any potentially fatal drug, maximum supportive care, and a restricted and tailored antibiotic, medical and surgical treatment regimen confined mortality to 21%, whereas prognosis scores like APACHE II and SCORTEN predicted mortality of 22 and 30%, respectively. A positive contribution of selective digestive decontamination is suggested but has yet to be established. CONCLUSIONS: Because of a potentially fatal outcome, fast referral of a patient suspected of TEN to a specialized centre (mostly a burns unit or specialized dermatology centre) for expert wound management and tailored comprehensive care is strongly advised and contributes to survival.     

The geriatric prosthesis as metaphor: a clinical note.

This clinical note describes a 96-year-old patient who wears a lengthening prosthesis in connection with the shortening of his leg which occurred after osteomyelitis of his left knee at the age of six years. The prosthesis was made and issued to him when he was twelve years old, and had never been replaced. The considerations that need to be made when replacing the prosthesis of an elderly patient are discussed. In the case described, the prosthesis is replaced by a model that has no fundamental changes from the original. The better fit improves walking considerably and the patient is able to move about safely again using a walking frame.     

Histologic distinction between malignant mesothelioma,benign pleural lesion and carcinoma metastasis

Summary Thirty men and 7 women with malignant mesothelioma seen at the Free University Hospital from 1st January 1960 until 1st July 1981 were reviewed.The histological, histochemical and morphometrical findings are reported. These findings are compared with 25 cases of pleural metastatic carcinoma and 25 cases of reactive pleural lesions.Fourty-nine percent of malignant mesotheliomas produced hyaluronic acid, however all cases of pleural metastatic carcinomas failed to produce this substance. All cases of malignant mesothelioma were D-PAS negative while 15 cases of pleural metastatic carcinoma showed reactivity to D-PAS. All cases of malignant mesothelioma and 9 cases of metastases were CEA negative.To distinguish malignant mesothelioma from metastases it is advisable to perform the D-PAS staining first. If it is negative mesothelioma can be confirmed by showing hyaluronic acid activity. A positive CEA staining rules out mesothelioma. In our study it was shown that with these methods 18 of 37 mesotheliomas could be identified with certainty, and 22 of the 25 carcinoma metastases.Morphometrically the malignant mesotheliomas could not be distinguished from the metastases, however the reactive pleural lesions had smaller nuclei than the malignant cells with mean values below 30 mu². In the malignant cases these values had a range from 36 to 101 mu².In distinguishing between reactive pleural lesions and malignant mesothelioma the production of hyaluronic acid points to the malignant character of the lesion.Thus histochemistry and immunostaining are important in the distinction of malignant mesothelioma from metastases, while the value of morphometry lies mainly in the separation of reactive lesions from malignant mesothelioma.     

Neural networks involved in mathematical thinking: evidence from linear and non-linear analysis of electroencephalographic activity

Using linear and non-linear methods, electroencephalographic (EEG) signals were measured at various brain regions to provide information regarding patterns of local and coordinated activity during performance of three arithmetic tasks (number comparison, single-digit multiplication, and two-digit multiplication) and two control tasks that did not require arithmetic operations. It was hypothesized that these measures would reveal the engagement of local and increasingly complex cortical networks as a function of task specificity and complexity. Results indicated regionally increased neuronal signalling as a function of task complexity at frontal, temporal and parietal brain regions, although more robust task-related changes in EEG-indices of activation were derived over the left hemisphere. Both linear and non-linear indices of synchronization among EEG signals recorded from over different brain regions were consistent with the notion of more "local" processing for the number comparison task. Conversely, multiplication tasks were associated with a widespread pattern of distant signal synchronizations, which could potentially indicate increased demands for neural networks cooperation during performance of tasks that involve a greater number of cognitive operations.     

Oligosaccharides from human milk block binding and activity of the Escherichia coli heat-stable enterotoxin (STa) in T84 intestinal cells

Enterotoxin-producing Escherichia coli are major causes of pediatric diarrhea in developing countries. The heat-stable enterotoxin of Escherichia coli (STa) causes diarrhea by virtue of its ability to bind to and stimulate intestinal membrane-bound guanylate cyclase, generating cyclic GMP (cGMP). Previous work showed that a fucosylated oligosaccharide fraction of human milk was able to protect suckling mice from the secretory effects of STa, but the mechanism of the protection could not be determined. Oligosaccharide fractions from human milk were tested for their ability to block the biochemical effects of STa in T84 cells, a human colon carcinoma line responsive to the toxin. Total and fucosylated oligosaccharide fractions were found to inhibit STa-stimulated guanylate cyclase activity in T84 cell membranes and cGMP production in intact T84 cells by 60-80%. In addition, the total oligosaccharide fraction and the fucosylated oligosaccharide fraction inhibited 125I-STa binding significantly (17% and 27% inhibition, respectively). These findings demonstrate the protective activity of human milk oligosaccharides against STa in a human-derived cell line and show that the biochemical step blocked by oligosaccharides is STa-mediated stimulation of guanylate cyclase. This represents a novel mechanism by which human milk oligosaccharides protect against diarrhea.     

A novel strategy for the isolation of defined pyrG mutants and the development of a site-specific integration system for Aspergillus awamori

A homologous gene transfer system for Aspergillus awamori for site-specific integration is described, based on two components. First, a defined A. awamori pyrG mutant strain constructed by a selection strategy for gene-replacement in fungi. Second, a vector with a homologous pyrG selection marker containing a defined mutation at a site different from that of the mutations in the pyrG gene of the defined mutant strain. Defined mutation in the A. awamori pyrG gene, isolated from a genomic library by heterologous hybridisation with the A. niger pyrG gene as a probe, were introduced by specifically altering sequences at restriction sites in the coding region of the gene. After transformation of the A. awamori wild-type strain with vectors containing these mutated pyrG genes, and selection for 5-fluoro-orotic acid resistance (5-FOA^R), on the average 60% of the 5-FOA^R colonies originated from replacement of the wild-type pyrG gene by the mutated pyrG allele. After transformation of a mutant strain, carrying a mutation near the 5 end of the pyrG gene with vectors containing a mutation near the 3 end of the pyrG gene, 35% of the resulting transformants contained one copy of the vector at the pyrG locus.