Background: Morphine consumption after a given surgical procedure can vary considerably. Studies show that single nucleotide polymorphism involving the nucleotide position 118 at exon 1 of the m-opioid receptor gene (OPRM1) may play a role in mediating the effects of opioids. This study was performed to correlate the A118G polymorphism at OPRM1 with morphine consumption in patients undergoing total knee arthroplasty. Methods: Post-operative pain was relieved by patient-controlled analgesia (PCA). The analgesic effect was evaluated using a visual analogue scale. Side-effects, such as sedation, nausea and vomiting, and pruritus, were recorded systematically. The genotypes were determined by sequencing polymerase chain reactionamplified DNA. The differences in demographics and consumed morphine from the PCA device between the different genotypes were tested using one-way analysis of variance. The prevalence of side-effects from morphine and sex distribution were compared using the Kruskal-Wallis test. Results: One hundred and forty-seven patients were included in the study. Twenty-seven patients who required rescue analgesia were excluded; these patients did not differ demographically or

No abstract

Background: Tumor cells require proficient autophagy to meet high metabolic demands and resist chemotherapy, which suggests that reducing autophagic flux might be an attractive route for cancer therapy. However, this theory in clinical cancer research remains controversial due to the limited number of drugs that specifically inhibit autophagy-related (ATG) proteins.Methods: We screened FDA-approved drugs using a novel platform that integrates computational docking and simulations as well as biochemical and cellular reporter assays to identify potential drugs that inhibit autophagy-required cysteine proteases of the ATG4 family. The effects of ATG4 inhibitors on autophagy and tumor suppression were examined using cell culture and a tumor xenograft mouse model.Results: Tioconazole was found to inhibit activities of ATG4A and ATG4B with an IC50 of 1.3 µM and 1.8 µM, respectively. Further studies based on docking and molecular dynamics (MD) simulations supported that tioconazole can stably occupy the active site of ATG4 in its open form and transiently interact with the allosteric regulation site in LC3, which explained the experimentally observed obstruction of substrate binding and reduced autophagic flux in cells in the presence of tioconazole. Moreover, tioconazole diminished tumor cell viability and sensitized cancer cells to autophagy-inducing conditions, including starvation and treatment with chemotherapeutic agents.Conclusion: Tioconazole inhibited ATG4 and autophagy to enhance chemotherapeutic drug-induced cytotoxicity in cancer cell culture and tumor xenografts. These results suggest that the antifungal drug tioconazole might be repositioned as an anticancer drug or chemosensitizer.

Between January 1991 and December 2002, we treated 92 acute, displaced, closed humeral shaft fractures (AO classification type A). We used three fixation methods: dynamic compression plates (DCP) in 36 patients, Ender nails (EN) in 32 patients and interlocking nails (ILN) in 24 patients. The patients were followed for a minimum of 24 months. At one year, all fractures except two (one DCP/one ILN) had united. Patients treated with EN had shorter mean operation time, 51 (35-110) min; less mean blood loss, 70 (30-170) ml and shorter mean hospital stay, 5.8 (3-12) days. There were three iatrogenic radial nerve palsies: two in the DCP group and one in the ILN group. There was one wound infection. There were three cases with impingement of the shoulder but range of motion was restored after nail removal. For patients with multiple trauma or high operative risk, EN fixation served as a safer and faster procedure. ILN fixation offered a stable fixation via a smaller incision but more fracture comminution might happen.

This retrospective study investigated adjacent segments radiologically and clinically after posterolateral fusion of the lumbar spine with instrumentation. Thirty-two patients over 60 years old with a postoperative follow-up of at least 4 years were included. These patients all met the criteria of a postoperative symptom-free period of over 2 years, evident fusion mass seen on plain radiographs, and no implant breakage or loosening. There was 81.3% excellent and good clinical results (26/32). For all patients, flexion and extension views of the lumbar spine were done preoperatively and postoperatively. Adjacent segments below the fusion, above the fusion, and cranial to the above adjacent segment were examined. Three patients each with translation > 4 mm in adjacent segments were found in both the short and long (> or = 3 segments) fusion groups. The incidence was 16.7% (3/18) in the short fusion group and 21.4% (3/14) in the long fusion group. However, no statistically significant difference (p = 0.7878) was found according to the Fisher exact test. Comparing the effect of different types of instruments, there still was no statistically significant difference (p = 0.1161) between the VSP plate and Isola rod groups in inducing degeneration of adjacent segments after posterolateral fusion of the lumbar spine. After measuring the mobility of degenerated adjacent segments, relative hypermobility was more likely responsible for the accelerated degeneration rather than the absolute increase of mobility.