Bilateral Panner’s disease in sickle cell anaemia: Case report

Avascular necrosis is common in sickle cell disease in various vulnerable areas such as in the femoral or humeral heads. Panner’s disease however is described as avascular necrosis of the capitellum, which commonly occurs in a younger age group. It is a pathological process believed to be caused by interference in the blood supply to the growing capitellar epiphysis. A 17 year old boy with sickle cell disease presented with pain on pronation and supination of both elbows, particularly on the lateral side. These movements were restricted in both elbows. Plain radiograph of his elbows showed fragmentation of the capitellum with signs of revascularisation. We have performed a thorough literature search and have not found other reported cases of Panner’s avascular necrosis of the capitellum in association with sickle cell disease. We conclude that Panner’s disease is a possible complication of sickle cell anaemia

Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis

BACKGROUND: Observational studies have consistently shown that aspirin and non-steroidal anti-inflammatory drug (NSAID) use is associated with a close to 50% reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on other cancers have shown conflicting results. Therefore, we conducted a meta-analysis to evaluate the relationship between NSAID use and cancer other than colorectal. METHODS: We performed a search in Medline (from 1966 to 2002) and identified a total of 47 articles (13 cohort and 34 case-control studies). Overall estimates of the relative risk (RR) were calculated for each cancer site using random effects models. RESULTS: Aspirin use was associated with a reduced risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38–0.69), and 0.73; 95%CI (0.63–0.84)). Use of NSAIDs was similarly associated with a lower risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46–0.92) and RR,0.54; 95%CI (0.39–0.75)). Among other cancers, only the results obtained for breast cancer were fairly consistent in showing a slight reduced risk among NSAID and aspirin users (RR, 0.77; 95%CI (0.66–0.88), and RR, 0.77; 95%CI (0.69–0.86) respectively)). CONCLUSIONS: The results of this meta-analysis show that the potential chemopreventive role of NSAIDs in colorectal cancer might be extended to other gastrointestinal cancers such as esophagus and stomach. Further research is required to evaluate the role of NSAIDs at other cancers sites

The role of cadaveric simulation in talus fracture research: A scoping review.

BACKGROUND: Talus fractures are rare (<1% of all fractures), and their rarity limits the number of studies available to guide management. In instances such as this, cadaveric studies can play an important role. The purpose of this scoping review was to identify and describe the current body of literature on cadaveric studies of fractures of the talus. METHODS: Through multiple electronic database searches (Medline, Embase, Scopus) we identified a broad body of cadaveric research into talus fractures, and these were classified into 4 main themes. Study characteristics were summarised along with any descriptive results and conclusions. RESULTS: The search yielded 484 articles of which 19 met the inclusion criteria. They provide valuable insights into benefits and drawbacks of surgical approaches to the talus, particularly with regard to direct visualisation of anatomic reduction, and risks of neurovascular or tendon compromise. For talar neck fractures it is clear that cannulated screws offer superior fixation over plates, however, are inferior when considering anatomic reduction of the fracture. Direct visualisation of fracture reduction is far superior to intraoperative radiographic assessment, and mal-reduction leads to reduced subtalar joint range of motion, midfoot deformity, and increased joint contact pressures. CONCLUSIONS: This study provides a summary of the existing literature surrounding the use of cadaver studies in fractures of the talus. We have identified gaps in the literature, particularly surrounding strength of fixation of new locking plate fixation techniques

Fracture healing in HIV-positive populations.

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-alpha) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue

Phosphorylation of Amyloid Precursor Protein at Threonine 668 Is Essential for Its Copper-responsive Trafficking in SH-SY5Y Neuroblastoma Cells

Amyloid precursor protein (APP) undergoes post-translational modification, including O- and N-glycosylation, ubiquitination, and phosphorylation as it traffics through the secretory pathway. We have previously reported that copper promotes a change in the cellular localization of APP. We now report that copper increases the phosphorylation of endogenous APP at threonine 668 (Thr-668) in SH-SY5Y neuronal cells. The level of APPT668-p (detected using a phospho-site-specific antibody) exhibited a copper-dependent increase. Using confocal microscopy imaging we demonstrate that the phospho-deficient mutant, Thr-668 to alanine (T668A), does not exhibit detectable copper-responsive APP trafficking. In contrast, mutating a serine to an alanine at residue 655 does not affect copper-responsive trafficking. We further investigated the importance of the Thr-668 residue in copper-responsive trafficking by treating SH-SY5Y cells with inhibitors for glycogen synthase kinase 3-β (GSK3β) and cyclin-dependent kinases (Cdk), the main kinases that phosphorylate APP at Thr-668 in neurons. Our results show that the GSK3β kinase inhibitors LiCl, SB 216763, and SB 415286 prevent copper-responsive APP trafficking. In contrast, the Cdk inhibitors Purvalanol A and B had no significant effect on copper-responsive trafficking in SH-SY5Y cells. In cultured primary hippocampal neurons, copper promoted APP re-localization to the axon, and this effect was inhibited by the addition of LiCl, indicating that a lithium-sensitive kinase(s) is involved in copper-responsive trafficking in hippocampal neurons. This is consistent with APP axonal transport to the synapse, where APP is involved in a number of functions. We conclude that copper promotes APP trafficking by promoting a GSK3β-dependent phosphorylation in SH-SY5Y cells