Characterization of hyaluronan and TSG‐6 in skin scarring: differential distribution in keloid scars,normal scars and unscarred skin

Background Hyaluronan (HA) is a major component of the extracellular matrix (ECM) with increased synthesis during tissue repair. Tumour necrosis factor‐stimulated gene‐6 (TSG‐6) is known to catalyze the covalent transfer of heavy chains (HC1 and HC2) from inter‐α‐inhibitor (IαI) onto HA, and resultant HC?HA complexes have been implicated in physiological and pathological processes related to remodelling and inflammation. Objective The aims of this study were to determine the expression of HA, TSG‐6 and the IαI polypeptides in unscarred skin, normal scars and keloid scars. Methods Formalin‐fixed paraffin‐embedded sections of unscarred skin, normal scars and keloid scars were prepared from patient samples collected during scar revision surgery. Haematoxylin and eosin, as well as immunofluorescent staining for HA, TSG‐6 and the three polypeptide chains of IαI (i.e. HC1, HC2 and bikunin) were performed. Results All skin types stained positive for TSG‐6, HC1, HC2 and bikunin, associated with keratinocytes, fibroblasts and skin appendages all in close proximity to HA. Keloid lesions showed altered HA organization patterns compared with unscarred skin and normal scars. TSG‐6 staining was significantly more intense in the epidermis compared with the dermis of all sample types. There was a significant reduction in TSG‐6 levels within keloid lesions compared with the dermis of unscarred skin (P = 0.017). Conclusion TSG‐6 is expressed in unscarred skin, where its close association with HA and IαI could give rise to TSG‐6‐mediated HC?HA formation within this tissue. A reduction in the beneficial effects of TSG‐6, caused by diminished protein levels in keloid lesions, could contribute to this abnormal scarring process.     

Recurrence of unexpected infant death

Families which had experienced two or more unexpected infant deaths were the subject of detailed confidential enquiries, including necropsy examination. Cases were derived from two main sources: first, deaths occurring during a nationwide programme of support for families with a subsequent baby (8 families) plus 2 families from a scries of confidential enquiries in Sheffield, and second, direct referrals from paediatricians (17 families). Fifty-seven deaths were studied. Twenty-four families had experienced 2 and three had experienced 3 deaths: 11 deaths (19%) were found to be adequately explained by history or post-mortem findings; 7 (12%) were probably accidental; 31 (55%) were most probably due to an action by one of the parents (filicide); only 5 (9%) were considered to be true or idiopathic sudden infant death syndrome; in 3 (5%) cases there was insufficient information to draw a conclusion. Five (18%) of the families lived in circumstances of serious social deprivation. A history of psychiatric illness was present in one or both parents in 18 (67%) of the families.     

Psoralen–ultraviolet A vs. narrow-band ultraviolet B phototherapy for the treatment of vitiligo

BACKGROUND: Although many treatment modalities have been tried for the treatment of vitiligo, none is uniformly effective. Psoralen phototherapy (psoralen ultraviolet A (PUVA)) is established as efficacious treatment for vitiligo. Recently, narrow-band UVB (NBUVB) has been reported to be an effective and safe therapeutic option in patients with vitiligo. OBJECTIVE: To compare the efficacy of PUVA and NBUVB in the treatment of vitiligo. DESIGN AND SETTING: Retrospective analysis of 69 patients with vitiligo who were treated either with PUVA or NBUVB at the pigmentary clinic of the Dermatology Department of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. OUTCOME MEASURES: The following variables were compared between the two groups of patients: repigmentation status, number of treatments for marked to complete repigmentation in existing lesions, appearance of new lesions or increase in size of existing lesions, adverse effect of therapy, stability of repigmentation and colour match. RESULTS: In PUVA-treated group, 9 patients showed marked to complete repigmentation (23.6%) and 14 patients showed moderate improvement (36.8%), whereas in NBUVB-treated group, 13 patients showed marked to complete repigmentation (41.9%) and 10 patients showed moderate improvement (32.2%). A statistically significantly better stability and colour match of repigmentation with surrounding skin was seen in NBUVB-treated patients. CONCLUSION: We showed that NBUVB is more effective than PUVA and repigmentation induced with NBUVB is statistically significantly more stable.     

Superficial granulomatous pyoderma: an idiopathic granulomatous cutaneous ulceration

A 70-year-old male with a superficial granulomatous ulcer is reported. Histopathological findings were the same as those described for superficial granulomatous pyoderma, a recognized variant of classic pyoderma gangrenosum. The differences between pyoderma gangrenosum and its variant superficial granulomatous pyoderma are highlighted.     

Increased Pyridinoline Cross‐Link Levels in Fibrosis is Accomplished by TGFβ Induced Lysyl Hydroxylases 2B Expression

Differentiation of fibroblasts into contractile, α‐smooth muscle actin (α‐SMA) expressing myofibroblasts depends on the action of the cytokine TGFβ in conjunction with mechanical tension. The goal of this study was to assess whether mechanical stress may play a role in activating TGFβ. Previous studies have shown that myofibroblasts secrete TGFβ1 as a large latent complex, consisting of the latency associated protein (LAP), the latent TGFβ1 binding protein (LTBP‐1) and TGFβ1. LTBP‐1 targets the small latent complex of LAP and TGFβ1 to the extracellular matrix (ECM), providing a stock of latent TGFβ1. To reveal the mechanisms triggering the release of active TGFβ1 from LAP and LTBP‐1, myofibroblasts were cultured on flexible silicone membranes for 3d before being subjected to unique 5% uniaxial stretch. After stress application we observed the course of TGFβ1 activation over 24 h by quantifying luciferase synthesis under the control of the TGFβ‐inducible PAI‐1 promoter. TGFβ activation showed two distinct peaks 1 h and 6 h after stretch. TGFβ1 mRNA levels were increased after 6 h as assessed by semi‐quantitative RT‐PCR. To further determine if rapidly activated TGFβ1 was released from ECM stores, we stretched myofibroblast‐derived ECM after cells have been removed by desoxycholate or EDTA treatment. Finally, we assessed the importance of the actin cytoskeleton in TGFβ1 activation by stretching Triton‐X‐100‐ and cytochalasin‐D‐treated myofibroblasts. Our results suggest that mechanical activation of TGFβ in myofibroblast culture requires cell activity and a functional cytoskeleton.     

Hip joint range of motion reduction in sports-related chronic groin injury diagnosed as pubic bone stress injury

Traumatic osteitis pubis is a non-specific entity that relates to chronic groin injury and has recently been described as being akin to a pubic bone stress injury. It is uncertain whether or not reduction of hip joint range of motion occurs in traumatic osteitis pubis. The purpose of this study was to establish whether there is a reduction of hip range of motion in athletes who have chronic groin injury diagnosed as pubic bone stress injury. A case-control study was performed whereby 89 Australian Rules footballers underwent, with clinical history unknown, clinical and MRI examination of the groin region. Clinical criteria (pain with tenderness) and MR-criteria (pubic bone marrow oedema) were used for diagnosis of pubic bone stress injury. End-range internal and external rotation hip motion was measured using a goniometer. Athletes with and without symptoms were compared, as were athletes with current symptoms with athletes who had recovered from their groin pain episode. Chronic groin injury was diagnosed in 47 athletes with 37 having pubic bone stress injury. Thirteen athletes had previous groin injury. A reduction of internal and external hip range of motion was demonstrated in athletes with pubic bone stress injury (p < 0.05) and in athletes who had current symptoms compared to those who had recovered from their groin pain episode (p < 0.05). A reduction in hip range of motion was evident in athletes with chronic groin injury diagnosed as pubic bone stress injury. There may be a role for increasing hip range of motion in rehabilitation.