Mild Mechanical Trauma Research Articles

A Case of Epidermolysis Bullosa Simplex (Dowling-Meara 1 Type) in Newborn

Epidermolysis bullosa is a rare genetic skin disease in which skin easily peels off and blisters are formed with mild mechanical trauma. It is classified into simple, borderline, dysmorphic, and mixed type. These four subtypes are further classified according to the location of gene mutation and genetic patterns. Epidermolysis bullosa simplex (EBS) is characterized by separation in the epidermal or subepidermal layer. And it is mostly caused by mutation of keratin 5 (KRT5) and KRT14 genes. Recently, genetic test has become increasingly important for diagnosis, confirming subtypes and genetic counseling. And there are moderate correlation exists between the EBS phenotype and genotype. Here, we report a case of 2-day-old boy with EBS Dowling-Meara type (EBS-DM) diagnosed by mutation analysis in KRT14.

The relationship between quality of life and coping strategies of children with EB and their parents

BackgroundEpidermolysis bullosa (EB) is a group of rare genetic skin disorders that primarily manifest as blisters and erosions following mild mechanical trauma. Despite the crucial role of the parents of children with EB in managing the disease, studies focusing on the parent–child relationship remain a gap in the literature. To address this gap, the current quantitative study, involving 55 children with all types of EB and 48 parents, assessed the relationship between their quality of life and coping strategies. Quality of life was measured with the Pediatric Quality of Life Inventory and TNO-AZL Questionnaire for Adult’s Health- related Quality of Life, and coping strategies were assessed with the Coping with a Disease Questionnaire. The majority of the analyses were descriptive and the results were interpreted qualitatively because of the small sample size.ResultsOverall, the quality of life of children with EB and that of their parents was somewhat lower compared with the quality of life of healthy children and adults. Children with EB who more frequently used emotional reactions and cognitive-palliative strategies to cope with the disease demonstrated lower levels of emotional and social functioning, while children who showed more acceptance and distancing showed higher levels of functioning on all domains. Parents who frequently demonstrated emotional reactions reported lower levels of social functioning and experienced more depressive emotions and anger. Parents who used more avoidance showed higher levels of positive emotions. Within parent–child dyads, acceptance, cognitive-palliative strategies and distancing were positively related. Children’s emotional and social functioning were negatively associated with their parents’ depressive emotions. Parents’ acceptance was linked to higher physical functioning in children, whereas children’s avoidance was linked to a lower level of anger in parents.ConclusionChildren who are able to accept the disease or distance themselves from it appear to be better off in contrast to those who tend to engage in the cognitive-palliative strategies and expressing emotional reactions. Parents seem to be better off when they are able to use avoidance in contrast to those who tend to show emotional reactions. Further research is needed to substantiate these findings.

Biophysical mechanisms of traumatic brain injuries.

Despite years of effort to prevent traumatic brain injuries (TBIs), the occurrence of TBI in the United States alone has reached epidemic proportions. When an external force is applied to the head, it is converted into stresses that must be absorbed into the brain or redirected by a helmet or other protective equipment. Complex interactions of the head, neck, and jaw kinematics result in strains in the brain. Even relatively mild mechanical trauma to these tissues can initiate a neurochemical cascade that leads to TBI. Civilians and warfighters can experience head injuries in both combat and noncombat situations from a variety of threats, including ballistic and blunt impact, acceleration, and blast. It is critical to understand the physics created by these threats to develop meaningful improvements to clinical care, injury prevention, and mitigation. Here the authors review the current state of understanding of the complex loading conditions that lead to TBI and characterize how these loads are transmitted through soft tissue, the skull and into the brain, resulting in TBI. In addition, gaps in knowledge and injury thresholds are reviewed, as these must be addressed to better design strategies that reduce TBI incidence and severity.

Quality of life among adults with epidermolysis bullosa living with a gastrostomy tube since childhood.

Epidermolysis bullosa (EB) is a rare genetic condition characterized by blistering to the skin and internal mucous membranes arising from mild mechanical trauma. The impact on those affected can be significant. They might have increased nutritional requirements because of blistering, chronic wounds, infection, and loss of exudates, and nutritional intake might be compromised because of oropharyngeal blistering and strictures, resulting in malnutrition in many patients. Placement of gastrostomy tubes can help some patients meet nutritional requirements. We report a recent study on how EB patients and their families approached the issue of whether to have a gastrostomy tube placed and how such tubes affect quality of life. Our findings include important insights for clinicians and families about how patients experience life with a gastrostomy. We show how the process of consent can be improved and how patients with a gastrostomy tube can feel more in control of their lives.

Risk factors and clinical features of craniocervical arterial dissection

Craniocervical arterial dissection is one of the most common causes of ischaemic stroke in young people and is occasionally associated with neck manipulation. Identification of individuals at risk will guide risk management. Early recognition of dissection in progress will expedite medical intervention. Study aims were to identify risk factors and presenting features of craniocervical arterial dissection. Medical records of patients from the Hunter region of New South Wales, Australia aged ≤ 55 years with radiographically confirmed or suspected vertebral or internal carotid artery dissection, were retrospectively compared with matched controls with stroke from some other cause. Records were inspected for details of clinical features, presenting signs and symptoms and preceding events. Records of 47 dissection patients (27 males, mean age 37.6 years) and 43 controls (22 males, mean age 42.6 years) were inspected. Thirty (64%) dissection patients but only three (7%) controls reported an episode of mild mechanical trauma, including manual therapy, to the cervical spine within the preceding three weeks. Mild mechanical trauma to the head and neck was significantly associated with craniocervical arterial dissection (OR 23.53). Cardiovascular risk factors for stroke were less evident in the dissection group (<1 factor per case) compared to the controls (>3).

Rapid Growth of Merkel Cell Carcinoma During Etanercept Treatment of Psoriatic Arthritis: Cause or Coincidence?

Merkel cell carcinoma (MCC) is an uncommon malignancy originating in epidermis. The anti-tumour necrosis factor (TNF)-α is used to treat psoriasis, rheumatoid arthritis and other inflammatory diseases. We report here a case of MCC in a relatively young patient that showed exceptionally rapid progression, which is uncommon for this type of tumour. The tumour appeared after 18 months of etanercept treatment. Cessation of its rapid growth was associated with interruption of anti-TNF-α treatment. CASE REPORT A 50-year-old white woman was referred to our clinic with an erythematous nodular lesion on her neck. Approximately 3 months previously she had first noticed a small (diameter approximately 1.5 cm) nodule that had rapidly increased in size and consistency and was soon associated with bleeding episodes following mild mechanical trauma. Physical examination revealed a shiny, firm, non-tender red polypoid nodule, approximately 2 × 2 cm in size with a wide erythematous base and no clinical lymphadenopathy (Fig. 1a). The lesion was scheduled for a diagnostic incisional biopsy. At the general physical examination the patient was in good health with no specific pathological signs or symptoms, apart from psoriatic arthritis without skin manifestations. This condition had been treated during the preceding 18 months with injections of etanercept (50 mg/week), with a good clinical response. The patient stated that she had never used any other immunosuppressive drugs or had phototherapy. Two weeks after visiting our clinic, at the time scheduled for the incisional biopsy, the lesion appeared markedly enlarged (4 × 3 cm) and the patient reported pain at the site of the tumour and in adjacent neck tissue (Fig. 1b). At that time, etanercept therapy was discontinued and the patient was given 8 mg/day corticosteroid and 7.5 mg methotrexate every 10 days. Fifteen days after the biopsy, when the stitches were removed, no further growth of the tumour was observed. The patient reported that the lesion had stopped growing 2 days after the withdrawal of etanercept therapy. The histopathological diagnosis was MCC. The patient was referred to the plastic surgery department for removal of the lesion. On physical examination, no local or regional lymph nodes were detected and blood test results were normal. A computed tomography (CT) scan of the thorax and of abdomen detected no lesions. However, despite excision with wide margins, the patient developed laterocervical locoregional lymph nodal metastases 6 months later. She died 16 months after the diagnosis from systemic metastases due to MCC.

Gene dosage effect of p.Glu170Lys mutation in the KRT5 gene in a Polish family with epidermolysis bullosa simplex

Epidermolysis bullosa simplex (EBS) is a genetic skin disorder characterized by the formation of blisters in response to mild mechanical trauma. It is caused predominantly by autosomal dominant mutations in the KRT5 or KRT14 gene, encoding keratin 5 and keratin 14, respectively [1]. The majority of KRT5 and KRT14 mutations result in substitution of conserved amino acid residues and the abnormal keratin molecules have a deleterious dominant-negative effect on the assembly of keratin filaments. Only single documented cases of EBS with autosomal recessive inheritance have been described so far [1].

The human G93A-SOD1 mutation in a pre-symptomatic rat model of amyotrophic lateral sclerosis increases the vulnerability to a mild spinal cord compression

BackgroundTraumatic injuries can undermine neurological functions and act as risk factors for the development of irreversible and fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). In this study, we have investigated how a mutation of the superoxide dismutase 1 (SOD1) gene, linked to the development of ALS, modifies the acute response to a gentle mechanical compression of the spinal cord. In a 7-day post-injury time period, we have performed a comparative ontological analysis of the gene expression profiles of injured spinal cords obtained from pre-symptomatic rats over-expressing the G93A-SOD1 gene mutation and from wild type (WT) littermates.ResultsThe steady post-injury functional recovery observed in WT rats was accompanied by the early activation at the epicenter of injury of several growth-promoting signals and by the down-regulation of intermediate neurofilaments and of genes involved in the regulation of ion currents at the 7 day post-injury time point. The poor functional recovery observed in G93A-SOD1 transgenic animals was accompanied by the induction of fewer pro-survival signals, by an early activation of inflammatory markers, of several pro-apoptotic genes involved in cytochrome-C release and by the persistent up-regulation of the heavy neurofilament subunits and of genes involved in membrane excitability. These molecular changes occurred along with a pronounced atrophy of spinal cord motor neurones in the G93A-SOD1 rats compared to WT littermates after compression injury.ConclusionsIn an experimental paradigm of mild mechanical trauma which causes no major tissue damage, the G93A-SOD1 gene mutation alters the balance between pro-apoptotic and pro-survival molecular signals in the spinal cord tissue from the pre-symptomatic rat, leading to a premature activation of molecular pathways implicated in the natural development of ALS.

Functional testing of keratin 14 mutant proteins associated with the three major subtypes of epidermolysis bullosa simplex.

Epidermolysis bullosa simplex (EBS) is a group of autosomal dominantly inherited skin disorders characterized by the development of intra-epidermal skin blisters on mild mechanical trauma. The three major clinical subtypes (Weber-Cockayne, Koebner and Dowling-Meara) are all caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) gene. Previously, we identified three novel KRT14 missense mutations in Danish EBS patients associated with the three different forms of EBS (1). The identified KRT14 mutations represent the full spectrum of the classical EBS subtypes. In the present study we investigated these mutations in a cellular expression system in order to analyse their effects on the keratin cytoskeleton. KRT14 expression vectors were constructed by fusing the nucleotide sequence encoding the FLAG reporter peptide to the 3' end of the KRT14 cDNA sequences. The expression vectors were transiently transfected into normal human primary keratinocytes (NHK), HaCaT or HeLa cells in order to analyze the ability of the mutant K14 proteins to integrate into the existing endogenous keratin filament network (KFN). No effect on the keratin cytoskeleton was observed upon transfection of NHK with the various K14 constructs neither with nor without a subsequently induced heat-stress. In contrast, all constructs, including wild-type K14, caused collapse of the endogenous KFN in a small fraction of the transfected HeLa and HaCaT cells. However, overexpression of the mutation associated with the most severe form of the disease, EBS Dowling-Meara, resulted in a higher number of transfected HaCaT cells with KFN collapse (P < 0.001). Thus, although a background KFN perturbance was observed upon transfection with the wild-type K14 construct, the mutant protein associated with the most severe form of EBS worsened the KFN perturbation significantly compared with the mutant proteins associated with the milder forms of the disease and the normal K14 protein. This shows that the clinical severity of disease-associated mutations identified in patients can be tested using this expression system, although it can not at present be used to discriminate between the milder forms. Assessment of the endogenous K14 protein expression in NHK and HaCaT cells indicated that the higher level of endogenous keratin expression in NHK might make these cells more resistant to perturbation of the keratin cytoskeleton by overexpressed K14 protein than HaCaT cells.

Expression of a Truncated Keratin 5 May Contribute to Severe Palmar–Plantar Hyperkeratosis in Epidermolysis Bullosa Simplex Patients

Epidermolysis bullosa simplex are dominant disorders of skin fragility characterized by intraepidermal blistering upon mild mechanical trauma. Skin fragility is caused by expression of either an abnormal keratin 5 or an abnormal keratin 14 protein, which compromises the structure and function of the keratin cytoskeleton of basal cells. We report an epidermolysis bullosa simplex patient with a novel single base substitution (A-->T1414) that changes the lysine residue at amino acid 472 to a non-sense codon (K472X). This change predicts the synthesis of a truncated keratin 5, missing 119 amino acids, including the entire tail domain and the highly conserved KLLEGE motif at the carboxy terminus of the 2B domain of the central rod. Expression of an altered keratin 5, of predicted mass and pI for the product of the K472X allele, was documented by one- and two-dimensional western blots of protein extracts from patient skin. Ultrastructural analysis of the patient's nonhyperkeratotic skin was remarkable for basal keratinocytes with dense and irregular keratin filaments proximal to the basement membrane. Keratinocytes, transfected with a cDNA carrying the A-->T1414 non-sense mutation, overexpressed a truncated keratin 5, and showed a disorganized and collapsed keratin filament cytoskeleton. This is the second epidermolysis bullosa simplex patient reported with a premature termination mutation in the KLLEGE motif. The remarkable occurrence of severe palmar--plantar hyperkeratosis in both patients suggests that the keratin 5 tail domain may have unrecognized, but important, normal functions in palmar-plantar tissues.

Regeneration in large blood vessels following mild mechanical trauma. An electron microscopy study.

Regeneration in large blood vessels following mild mechanical trauma. An electron microscopy study.

Ultrastructural changes of large rabbit blood vessels following mild mechanical trauma

The morphological changes of the abdominal aorta and inferior vena cava were studied from one to seven days following application of mild mechanical trauma (compression of the vessel wall with a clamp covered by rubber tubing). Both light microscopy of silver-stained surface preparations and electron microscopy of sectioned vessels were performed. The following morphological changes were observed in both the vena cava and abdominal aorta at all time sequences investigated: focal necrosis, abnormal overlapping of endothelial cells and pseudopod-formation from them usually directed into the lumen; and pseudopod-formation from medial smooth muscle cells, often passing into the intima via fenestrations in the elastic membrane. Leucocytes accumulated in the vessel wall only in the vena cava, whereas the ground substance increased only around myointimal cells of the aorta. The genesis and significance of the above changes are discussed.

Electron micrographic observations on the emigration of leucocytes.

Electron micrographs have been made of small venules in the rat's mesentery after exposure to mild mechanical trauma. Stages in the migration of blood cells are illustrated.Polymorphonuclear leucocytes seem sometimes to penetrate the endothelium at or near cell junctions, but they may also be able to penetrate the endothelial cytoplasm at other points. After the passage of the leucocytes through the endothelium no sign of a passage way can be seen.The emigrating leucocytes may be held up for a time by the basement membrane of the endothelium or by the periendothelial tissues but these are eventually penetrated so that the leucocytes become free in the surrounding tissue.Eosinophils and probably monocytes were seen passing through the vessel walls apparently in a manner similar to that of the polymorphs.Red blood cells were seen in process of going through the endothelium but the pictures do not show whether they pass through it in holes made by leucocytes.