Keratinocyte conditioned medium abrogates the modulatory effects of IGF-1 and TGF-β1 on collagenase expression in dermal fibroblasts

Overexpression of wound healing-promoting factors such as transforming growth factor-1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) during the healing process has been implicated in the development of dermal fibrosis in patients following thermal injury, surgical incision, and deep trauma. However, the mechanism through which the expression of these two fibrogenic factors is slowed down and/or abrogated in the late stages of the healing process is not known. Here, we hypothesize that keratinocyte-releasable factors counteract the fibrogenic role of both IGF-1 and TGF-beta1 in fibroblasts. To test this hypothesis, the levels of collagenase (MMP-1), as an index for extracellular matrix degradation, in dermal fibroblasts in response to either keratinocyte-conditioned medium (KCM) or our recently identified keratinocyte-releasable stratifin in the presence and absence of either IGF-1, TGF-beta1, or both were evaluated. The results of Northern analysis showed a significant increase in collagenase mRNA expression in cells treated with KCM in the presence of both IGF-1 and TGF-beta1. The effect was, at least in part, due to keratinocyte-derived stratifin that was present in KCM. This was ascertained as the levels of MMP-1 mRNA were markedly reduced when cells were treated with stratifin-immuno-depleted KCM. The results of Western blot analysis showed an increase in the level of MMP-1 protein in stratifin-treated fibroblasts and this was consistent with the level of MMP-1 mRNA expression detected by Northern analysis. However, in contrast to KCM, whose efficacy on MMP-1 expression was modestly reduced by either IGF-1 and TGF-beta1, or a combination of both, these factors abrogated the MMP-1 stimulatory effect of stratifin in fibroblasts. In summary, the results of this study revealed that both stratifin and KCM stimulate the expression of MMP-1-in fibroblasts and this effect can be abrogated by either IGF-1, TGF-beta1, or a combination of both.     

Complement levels before and after dives with a high risk of DCS.

BACKGROUND: Previously, complement activation has been associated with decompression sickness (DCS). However data, both in humans and in animals, are controversial. Hypothesis: Complement activation and depletion occurs after exposure to the hyperbaric environment and is associated with increasing risk of DCS. METHODS: We obtained serological samples from 102 dives (120-300 feet of seawater) with a constant partial pressure of O2 set at 1.3 ATA in thirty-five U.S. Navy diver volunteers. Blood was obtained within one hour of diving and within one hour of surfacing. Plasma was extracted and analyzed for complement depletion. The risk of DCS was estimated using a validated model of DCS risk. RESULTS: Pre-post dive concentrations of C3a were significantly related to estimated risk of DCS (Figure 1), but the variation in predicted DCS explained by C3a was small (correlation co-efficient (r2 = 0.19, p < 0.0001). CONCLUSIONS: There was a reduction in total Ca3 levels in divers after exposure to dives with a high estimated risk of DCS. This decomplementation appeared to increase as the estimated risk of DCS increased.     

Precision grip function after free toe transfer in children with hypoplastic digits.

Although toe-to-hand transfer has a defined role in the management of congenital hand deformities, it remains unclear how well children integrate the transferred digits into physiological grasping. We analysed fingertip forces in the precision grip of 13 patients when lifting a test object more than three years after free toe transfer for absent or hypoplastic digits. Clinically, most patients showed normal sensibility of transferred digits, but active motion and pinch strength were limited as compared to the normal hand. For the control of fingertip forces, two key features of the normal two-digit opposition grip were seen in all operated hands: adaptation of grip force to object weight and parallel coordination of lift and grip forces. These physiological grasping strategies developed independently of the patients' age at the time of operation, which ranged from one to 13 years. In four patients, we observed increased tangential load forces with the operated hand due to misalignments in the application of fingertips on the grasp surfaces. Such forces lead to increased grip force requirements on both fingers that may overload transferred digits with limited motor function. The need for optimal alignment of the grip axis during toe-transfer surgery is emphasised.     

Cervical soft tissue imaging using a mobile CBCT scanner with a flat panel detector in comparison with corresponding CT and MRI data sets.

OBJECTIVE: The aim of this study was to evaluate soft tissue image quality of a mobile cone-beam computed tomography (CBCT) scanner with an integrated flat-panel detector. STUDY DESIGN: Eight fresh human cadavers were used in this study. For evaluation of soft tissue visualization, CBCT data sets and corresponding computed tomography (CT) and magnetic resonance imaging (MRI) data sets were acquired. Evaluation was performed with the help of 10 defined cervical anatomical structures. RESULTS: The statistical analysis of the scoring results of 3 examiners revealed the CBCT images to be of inferior quality regarding the visualization of most of the predefined structures. Visualization without a significant difference was found regarding the demarcation of the vertebral bodies and the pyramidal cartilages, the arteriosclerosis of the carotids (compared with CT), and the laryngeal skeleton (compared with MRI). Regarding arteriosclerosis of the carotids compared with MRI, CBCT proved to be superior. CONCLUSIONS: The integration of a flat-panel detector improves soft tissue visualization using a mobile CBCT scanner.     

Clinical outcome after D1 vs D2-3 gastrectomy for treatment of gastric cancer.

BACKGROUND: Clinical benefit from extended lymphadenectomy for gastric cancer remains controversial as a considerable variation exists between results of different studies. METHODS: 562 patients were treated at HUCH between 1987-2003, whereof 223 underwent gastrectomy with curative intent. Of these, 114 patients underwent subtotal/total gastrectomy with D1 (standard) lymphadenectomy and 109 patients had D2-3 (extended) lymph node dissection. The clinical outcome of these patients was analysed retrospectively. RESULTS: The incidence of surgical complications was 33.0% in D2-3 and 16.8% in D1 lymphadenectomy groups (p = 0.008). Abscess was the most common complication (11.0%) among D2-3 operated patients and haemorrhage (4.4%) in D1 group. Hospital mortality was 3.7% in D2-3 and 1.8% in D1 group (p = 0.438). The only statistically significant factor influencing the rate of complications was D2-3 lymphadenectomy (OR 2.620, 95% C.I. 1.375 to 4.991). D2-3 was associated with a longer postoperative hospital stay and operation time, greater blood loss and increased need for blood transfusions compared to D1. The 5-year survival was not statistically different between lymphadenectomy groups. CONCLUSION: It is justified to perform a D2-3 gastrectomy in Europe with a acceptable postoperative mortality but with a significant morbidity. Further studies are needed to assess the value of extended lymphadenectomy in gastric cancer.     

Follow up of patients with colorectal polyps: are the BSG guidelines being adhered to?

OBJECTIVE: The publication of the BSG guidelines in 2002 provided a framework for the follow up of patients with colorectal polyps. The aim of the present study was to determine whether they had, or were being correctly adhered to in a moderately sized District General Hospital. METHOD: A total of 598 patients were on the waiting list for colonoscopy at Airedale General Hospital (AGH) in February 2005. Of these, 203 were being followed up as a result of the previous finding of a polyp. RESULTS: Only 14.8% of patients had been or were being followed up according to the BSG guidelines. The majority of the 85.2% of patients who did not comply with follow up did so as a result of over investigation. Seventy-eight per cent of the low-risk group and 55% of the intermediate-risk group had been colonoscoped, or were waiting to have colonoscopy, too soon or too frequently according to the BSG guidelines. Twenty-four patients with hyperplastic polyps were being followed up incorrectly, as were 17 patients discovered to have a polyp pathology on flexible sigmoidoscopy. It was established that 131 extra colonoscopies had been, or were planned to be performed unnecessarily. CONCLUSION: These data have major implications with regard to patient safety, service provision and cost to the NHS.     

An intra-articular vascular malformation with a ganglion in a knee

We report a case of an intra-articular vascular malformation occurring simultaneously with a ganglion in a knee joint. We believe this to be the first reported case of an intra-articular vascular malformation occurring simultaneously with a ganglion. The malformation was cauterized resulting in resolution of knee pain. We suggest that vascular malformations be considered in the differential diagnosis of knee pain.