Digital papillary adenocarcinoma (DPAC) is a rare, aggressive cancer with significant metastatic potential which arises from digital sweat glands. We present a case of a DPAC managed with surgical ...excision and reconstruction with a reversed homodigital island flap.
Level of evidence: V
RNA-mediated gene silencing Pickford, A S; Cogoni, C
Cellular and molecular life sciences : CMLS
60, Številka:
5
Journal Article
Recenzirano
Odprti dostop
A number of gene-silencing phenomena including co-suppression discovered in plants, quelling in fungi and RNA interference in animals have been revealed to have steps in common. All occur in the ...cytoplasm at a post-transcriptional level with the mRNAs of target genes degraded in a sequence-specific manner. Small non-coding RNA molecules demonstrated to be mediators of these silencing phenomena have also been shown to mediate a parallel post-transcriptional gene silencing (PTGS) mechanism that regulates the expression of developmental genes, although in this latter mechanism, rather than being degraded, the translation of target mRNAs is inhibited. Both types of small RNA appear to be processed from longer double-stranded RNAs (dsRNAs) by a common endonuclease. RNAs may also operate as regulators of gene expression at a transcriptional level in the nucleus, via chromatin remodelling or RNA-directed DNA methylation. Methylation of promoter sequences leads to transcriptional gene silencing, while methylation of coding sequences by the same homology-dependent mechanism does not block transcription, but leads to PTGS. In some organisms, the RNA silencing signal may spread to other tissues inducing systemic RNA silencing.
To assess the thin-section computed tomographic (CT) findings of lymphocytic interstitial pneumonia.
The study included 22 patients (five men, 17 women; age range, 24-83 years; mean age, 50 years) ...with biopsy-proved lymphocytic interstitial pneumonia. The CT scans were obtained by using 1-3-mm collimation and reconstructed by using a high-spatial-frequency algorithm.
The predominant abnormalities consisted of areas of ground-glass attenuation and poorly defined centrilobular nodules present in all 22 patients and subpleural small nodules seen in 19 patients. Other common findings included thickening of bronchovascular bundles (n - 19), interlobular septal thickening (n = 18), cystic airspaces (n = 15), and lymph node enlargement (n = 15). Less common findings included large nodules, emphysema, airspace consolidation, bronchiectasis, architectural distortion, honeycombing, and pleural thickening.
Lymphocytic interstitial pneumonia is characterized by the presence of ground-glass attenuation, poorly defined centrilobular nodules, and thickening of the interstitium along the lymphatic vessels. Lymph node enlargement is more common than previously recognized; it was seen in 68% of patients.
A retrospective study was undertaken to review the outcomes of a consecutive series of patients treated using pyrocarbon surface replacement arthroplasty by the same surgeon. We analyzed the results ...of this procedure in 24 proximal interphalangeal (PIP) joints in 19 hands of 16 patients. The minimum follow-up was 3 years. The study showed that pyrocarbon PIP joint replacements provided excellent pain relief and high patient satisfaction. More than two-thirds of patients subjectively rated postoperative range of motion and functional outcomes as better than preoperatively. Objective assessment showed a modest improvement in the active range of motion, which did not achieve statistical significance, although we did observe a statistically significant increase in passive range of motion. The results are encouraging for those surgeons who seek an alternative to silicone implant PIP joint arthroplasty in high-demand patients.
Summary Visual images can enhance communication over a distance. In the UK, plastic surgery provides services over large distances by a ‘hub and spoke’ model. Telemedicine could help to increase the ...efficiency of service for plastic surgery patients. Telemedicine, along with the impending Electronic Patient Record system could combine to improve communication, patient triage, record keeping, audit and could lead to a better quality of clinical care. Another benefit could be significant cost savings. We report our experience of the introduction of telemedicine to a Regional Plastic Surgery Service. Our first study compared assessments from images and patient examinations, which gave us confidence in the use of images Jones SM, Milroy C, Pickford MA. Telemedicine in acute plastic surgical trauma and burns. Ann R Coll Surg Engl 2004; 86 :239–42. We proceeded to a 10-week evaluation of all 973 referrals to our unit. We found that the system was used for a wide variety of injuries and for 42% of the 452 patients where the system was available. Initial resistance was overcome by the ease of use of the system, with both receiving and referring clinicians reporting benefits. The third phase was a 12-week prospective cohort study of 996 patients comparing the referrals with and without the telemedicine system. The system was available for 389 patients, and used for 243 patients (63%). The groups were analysed by a chi squared test and confidence interval calculation. We demonstrated a significant difference in the initial management of patients, with 10% more being booked directly to our Day Surgery Unit. There was a decrease in number of occasions when we were unable to accept a patient due to a lack of capacity. We found no change in the patients being managed with telephone only advice. We found that telemedicine is a valuable method of providing useful preliminary information in the referral process for injured patients and often significantly modifies their treatment and/or management plan. This has implications for the use of Information Technology resources and potentially the delivery of healthcare in relation to the management of injured patients.
Congenital pseudarthrosis of the forearm bones (CPFBs) is rare, with only 106 reported cases, and is frequently associated with neurofibromatosis (NF). Approximately 5% of patients with NF develop ...pseudarthrosis, and 50% of patients with pseudarthrosis have NF. Achieving bone union is difficult in congenital pseudarthrosis. Many methods have been attempted, including casting, internal fixation with or without grafting, and electrical stimulation, but failure is frequent. Free vascularized fibular flaps (FVFs) have been used to bridge long bone defects since 1975 and in tibial pseudarthrosis since 1979. In CPFB, FVF is more successful than other methods in achieving union and is the current treatment of choice. Here, we presented three cases of forearm pseudarthrosis treated with FVF, reviewed the literature on CPFB, and discussed some technical aspects of FVF treatment. Three cases of congenital pseudoarthrosis were treated with free fibula flaps, diagnosed at ages of 7 years (ulna), 15 months (radius), and 9 years (radius and ulna). Two flaps were stabilized with intramedullary wires and latterly, one with compression plates. One persistent nonunion received revision nonvascularized bone grafting and plating. All patients achieved union by 11 months after index surgery. Reconstruction with vascularized fibula is the treatment of choice because it offers the highest published union rates and good functional results. Complete resection of the affected bone and stable fixation, latterly with compression plates are critical to success. Surgery is technically demanding, and complications are common. Secondary surgery may be required, but outcomes are favorable.
IV
Adhesive interactions involving CD44, the cell surface receptor for hyaluronan, underlie fundamental processes such as inflammatory leukocyte homing and tumor metastasis. Regulation of such events is ...critical and appears to be effected by changes in CD44 N-glycosylation that switch the receptor “on” or “off” under appropriate circumstances. How altered glycosylation influences binding of hyaluronan to the lectin-like Link module in CD44 is unclear, although evidence suggests additional flanking sequences peculiar to CD44 may be involved. Here we show using X-ray crystallography and NMR spectroscopy that these sequences form a lobular extension to the Link module, creating an enlarged HA binding domain and a formerly unidentified protein fold. Moreover, the disposition of key N-glycosylation sites reveals how specific sugar chains could alter both the affinity and avidity of CD44 HA binding. Our results provide the necessary structural framework for understanding the diverse functions of CD44 and developing novel therapeutic strategies.
Glioblastoma Multiforme is a highly aggressive brain tumour known for its heterogeneity and its vascularity. Published reports using in vivo and in vitro glioma models reveal that Matrix ...metalloproteinase-1 (MMP-1) over-expression induces angiogenesis. In other studies the involvement of the Protease Activated Receptor 1 (PAR1) in MMP-1's effect on tumour vessel formation has been suggested. MMP-1 expression is localised to glioma and endothelial cells with PAR1 expression mainly localised to endothelial cells in human glioma biopsies. MMP-3, also expressed in gliomas, is an activator of pro-MMP-1. Herein, we focused on the effects of MMP-3 activated MMP-1 and conditioned media from glioma cell lines cultured under hypoxic conditions to begin to examine mechanisms of MMP-1 induction of angiogenesis in an in vitro model of brain endothelial cell tube formation. Human brain endothelial cells, activated MMP-1, inhibitors (PAR1 and MMP-1) were used to investigate the possibility that MMP-1 acts through PAR1 to induce angiogenesis. This was accessed by measuring brain endothelial tube length, number of tube projections and the number of branch points. Conditioned media from glioma cell lines (SNB-19 and UP-007) cultured under either normoxic or hypoxic conditions were also tested in the absence/presence of inhibitors. PAR1 activation was examined by endothelial intracellular calcium release using live cell imaging following addition of MMP-1. Exogenous addition of MMP-3 activated MMP-1 to brain endothelial cells lead to a dose dependant increase in number of branch points and tube length (P less than or equal to 0.05). MMP-1 inhibition prevented this increase and inclusion of a PAR1 inhibitor resulted in preventing MMP-1's effect, suggesting MMP-1 may function through PAR1 to drive angiogenesis. Endothelial cells treated with conditioned media obtained from glioma cell lines resulted in a significant increase in all measures of tube formation, with the most significant effect being on tube number using media from glioma cells grown under hypoxia (P less than or equal to 0.05). MMP-1 and PAR1 inhibition blocked these effects. Although it is well documented that MMP-1 is over-expressed in high grade gliomas, it has been unclear what role MMP-1 plays as its 'normal' ECM substrates are not typically found in gliomas or normal brain. Results from this study extend earlier data showing in vivo induction of angiogenesis and highlight a potential signaling pathway via PAR1 activation in glioma pathology.
PDF
