Wei-Tso Chia

Comparison of plates versus intramedullary nails for fixation of displaced midshaft clavicular fractures.

BACKGROUND We compare the use of plate and screws versus intramedullary nails in the operative management of patients with displaced midclavicular fractures. METHODS Between March 2006 and June 2007, we performed a retrospective comparison of a demographically balanced sample of 110 patients (aged 16-65 years) who had received either plates or nails for completely displaced midshaft clavicular fractures. RESULTS We selected 59 plate-fixed and 51 nail-fixed patients. There was no significant difference between the groups with respect to age, gender, height, dominant arm, fracture angulation, fracture shortening, total fracture displacement, or mechanism of injury. Outcomes were significantly higher in the plate group compared with the nail group for the length of hospital stay (4.6 days ± 2.1 days vs. 5.9 days ± 2.6 days, p = 0.006), operative blood loss (67.5 mL ± 36.2 mL vs. 127.9 mL ± 48.8 mL, p < 0.0001), and size of surgical wound (11.9 cm ± 4.4 cm vs. 22.3 cm ± 4.5 cm, p < 0.0001). There was no significant difference in operative time, time to union, restoration of mobility (forward flexion, abduction, external rotation, and internal rotation), number of nonunions, number of malunions, infection, need for hardware removal, early mechanical failure, time to return to work, and Constant Shoulder and Disabilities of the Arm, Shoulder, and Hand functional scores. CONCLUSION Our results demonstrate no significant differences in functional outcome and nonunion rates between nails and plates fixation for displaced midshaft clavicular fractures.

An Implantable Depot That Can Generate Oxygen in Situ for Overcoming Hypoxia-Induced Resistance to Anticancer Drugs in Chemotherapy

In the absence of adequate oxygen, cancer cells that are grown in hypoxic solid tumors resist treatment using antitumor drugs (such as doxorubicin, DOX), owing to their attenuated intracellular production of reactive oxygen species (ROS). Hyperbaric oxygen (HBO) therapy favorably improves oxygen transport to the hypoxic tumor tissues, thereby increasing the sensitivity of tumor cells to DOX. However, the use of HBO with DOX potentiates the ROS-mediated cytotoxicity of the drug toward normal tissues. In this work, we hypothesize that regional oxygen treatment by an implanted oxygen-generating depot may enhance the cytotoxicity of DOX against malignant tissues in a highly site-specific manner, without raising systemic oxygen levels. Upon implantation close to the tumor, the oxygen-generating depot reacts with the interstitial medium to produce oxygen in situ, effectively shrinking the hypoxic regions in the tumor tissues. Increasing the local availability of oxygen causes the cytotoxicity of DOX that is accumulated in the tumors to be significantly enhanced by the elevated production of ROS, ultimately allaying the hypoxia-induced DOX resistance in solid malignancies. Importantly, this enhancement of cytotoxicity is limited to the site of the tumors, and this feature of the system that is proposed herein is unique.

Triptolide exerts anti-tumor effect on oral cancer and KB cells in vitro and in vivo

Triptolide (TPL), a diterpenoid triepoxide purified from the Chinese herb Tripterygium wilfordii Hook F, has been reported to potentiate the anti-tumor effect in various cancer cells. However, the effect of TPL on oral cancers is not yet evaluated. Herein we first demonstrate that TPL induces prominent growth inhibition and apoptosis in two oral cancer cell lines, SCC25 and OEC-M1 and in KB cells. Our results indicate that TPL induces a dose-dependent apoptosis of these cells at nanomolar concentration. Apoptosis signalings are both activated through time upon TPL treatment detected by elevated caspase-3, 8, 9 activities. In xenograft tumor mouse model, TPL injection successfully inhibits the tumor growth via apoptosis induction which was demonstrated by TUNEL assay. These results demonstrate that TPL exerts anti-tumor effect on oral cancer and KB cells and suggest further the potential of TPL combining with other chemotherapeutic agents or radiotherapy for advanced oral cancer.

Melatonin prolongs islet graft survival in diabetic NOD mice

Abstract:  Islet transplantation has been established as a potential therapy for type 1 diabetes. However, inflammation, allorejection, and on‐going autoimmune damage contribute to early graft loss and failure of islet transplantation. Melatonin is the major secretory product of the pineal gland during the dark period of each day and displays multifunctional properties including the regulation of circadian and seasonal rhythms, antioxidation reactions and immune modulation. Based on the immunosuppressive properties of melatonin, we investigated whether melatonin treatment prolonged the survival of islet grafts in non‐obese diabetic (NOD) mice. The mean islet graft survival time was 7.33 ± 1.51 and 7.75 ± 2.66 days in untreated controls and in the solvent‐treated animals, respectively. Strikingly, the mean survival time of islet grafts in recipients treated with melatonin (200 mg/kg/bw) was 17 ± 7.76 days. Moreover, melatonin treatment reduced the proliferation of splenocytes in NOD mice. Using a T1 and T2 double transgenic mouse model, we found that T helper 1 (Th1) cells in mice treated with melatonin were significantly decreased. The reduction of Th1 cells and T cell proliferation may result from an increase in the immunosuppressive cytokine IL‐10. Our results indicate that melatonin treatment suppresses autoimmune recurrence by inhibiting the proliferation of Th1 cells in NOD mice and thus prolongs the survival of syngeneic islet grafts.

Controlled Release of an Anti-inflammatory Drug Using an Ultrasensitive ROS-Responsive Gas-Generating Carrier for Localized Inflammation Inhibition

Inflammation is associated with many diseases, in which activated inflammatory cells produce various reactive oxygen species (ROS), including H2O2. This work proposes an ultrasensitive ROS-responsive hollow microsphere (HM) carrier that contains an anti-inflammatory drug, an acid precursor consisting of ethanol and FeCl2, and sodium bicarbonate (SBC) as a bubble-generating agent. In cases of inflamed osteoarthritis, the H2O2 at low concentration diffuses through the HMs to oxidize their encapsulated ethanol in the presence of Fe(2+) by the Fenton reaction, establishing an acidic milieu. In acid, SBC decomposes to form CO2 bubbles, disrupting the shell wall of the HMs and releasing the anti-inflammatory drug to the problematic site, eventually protecting against joint destruction. These results reveal that the proposed HMs may uniquely exploit biologically relevant concentrations of H2O2 and thus be used for the site-specific delivery of therapeutics in inflamed tissues.

Photothermal tumor ablation in mice with repeated therapy sessions using NIR-absorbing micellar hydrogels formed in situ

Repeated cancer treatments are common, owing to the aggressive and resistant nature of tumors. This work presents a chitosan (CS) derivative that contains self-doped polyaniline (PANI) side chains, capable of self-assembling to form micelles and then transforming into hydrogels driven by a local change in pH. Analysis results of small-angle X-ray scattering indicate that the sol-gel transition of this CS derivative may provide the mechanical integrity to maintain its spatial stability in the microenvironment of solid tumors. The micelles formed in the CS hydrogel function as nanoscaled heating sources upon exposure to near-infrared light, thereby enabling the selective killing of cancer cells in a light-treated area. Additionally, photothermal efficacy of the micellar hydrogel is evaluated using a tumor-bearing mouse model; hollow gold nanospheres (HGNs) are used for comparison. Given the ability of the micellar hydrogel to provide spatial stability within a solid tumor, which prevents its leakage from the injection site, the therapeutic efficacy of this hydrogel, as a photothermal therapeutic agent for repeated treatments, exceeds that of nanosized HGNs. Results of this study demonstrate that this in situ-formed micellar hydrogel is a highly promising modality for repeated cancer treatments, providing a clinically viable, minimally invasive phototherapeutic option for therapeutic treatment.

Surgical Treatment of Acute Acromioclavicular Joint Injuries Using a Modified Weaver-Dunn Procedure and Clavicular Hook Plate

Various surgical procedures have been described for the treatment of complete acromioclavicular joint dislocation, but no consensus exists on the optimal therapy. The aim of each type of procedure is to stabilize the clavicle by substitution of the ruptured coracoclavicular ligaments. Treatment modalities have changed with increasing understanding of the nature of the problem and the biomechanics of the joint. This article presents a method consisting of a modified Weaver-Dunn procedure and a clavicular hook plate for the operative management of acute acromioclavicular joint injuries.We performed a retrospective study of 46 patients who had undergone a modified Weaver-Dunn procedure with a clavicular hook plate for acute acromioclavicular joint injuries between July 2002 and December 2006. Average follow-up was 36.6 months (range, 24-46 months). There was 1 skin-deep infection, 1 dislocation of the hook, and 2 redislocations of the acromioclavicular joint. Thirteen patients had some calcification between the clavicle and the coracoid process, which did not cause loss of motion or other symptoms. All but 1 patient returned to work, and all but 1 returned to their preoperative activity level. The mean Constant score was 88.2 points. The mean Disabilities of the Arm, Shoulder, and Hand (DASH) score was 12.2 points.Treatment of acute acromioclavicular joint injuries using a modified Weaver-Dunn procedure and a clavicular hook plate showed good short-term clinical results with a low complication rate. Further investigation and long-term results are needed to confirm these preliminary findings.

Prospective analysis of a new minimally invasive technique for paediatric Gartland type III supracondylar fracture of the humerus

OBJECTIVE The purpose of this study was to introduce a minimally invasive surgery using mosquito forceps for achieving the reduction of severely displaced supracondylar fracture of the humerus in children and evaluate the clinical outcome. MATERIALS AND METHODS Gartland type III supracondylar fractures of the humerus in children under the age of 12 were analysed from January 2000 to January 2007 at our institute. The control group cases were selected by successful reduction using the standard technique described by Rockwood and Wilkins (2001). The others composed the study group. This study included chart reviews, radiographic images of both the antero-posterior and the lateral views, physical examination, and Mayo elbow performance index scores preoperative, postoperative, and final follow-up. RESULTS Evaluations were completed for 42 cases. The mean age was 6.9 years and the group consisted of 23 boys and 19 girls. The mean follow-up time was 34.5 months. Twenty-six cases were of injuries to the left side, and 16 were of injuries to the right. The Mayo elbow performance index score was excellent in both groups. Operation time in the control and study groups was 46 and 79min, respectively. There was one case of iatrogenic ulnar nerve injury each in the study and control group. One case of loss of reduction and another with a combination of ulnar nerve injury and loss of reduction were noted in the control group. All four cases had an excellent final outcome. No mosquito-forceps-related complication was found, and in the final follow-up, no cubitus varus was found. CONCLUSION Minimally invasive surgery with the assistance of mosquito forceps for the reduction of severely displaced supracondylar fracture of the humerus in children was shown to be a safe and effective alternative method. The final functional outcome was the same as that of the standard technique.

Transgenic expression of murine chemokine decoy receptor D6 by islets reveals the role of inflammatory CC chemokines in the development of autoimmune diabetes in NOD mice

Aims/hypothesisAutoimmune diabetes results from a progressive destruction of insulin-producing beta cells in the pancreatic islets by chemokine-attracted lymphocytes. Because islet cells in NOD mice produce chemokines during the development of autoimmune diabetes, we investigated the role of inflammatory CC chemokines in disease progression in these mice.MethodsWe generated a transgenic NOD mouse model that overproduces the inflammatory CC chemokine decoy receptor D6 in pancreatic islets.ResultsThe frequency of diabetes and insulitis scores of transgenic mice were decreased significantly, compared with non-transgenic control littermates. Transgenic expression of D6 (also known as Ccbp2) did not affect systemic lymphocyte development or alter: (1) the T cell subsets such as T helper (Th)1, Th2 and T regulatory cells; or (2) antigen-presenting cells such as dendritic cells or macrophages. The percentages and numbers of T and B lymphocytes were decreased significantly in the pancreas. Activation status, autoantigen-specific proliferation and diabetogenicity of lymphocytes were also markedly reduced.Conclusions/interpretationInflammatory CC chemokines play a critical role in the development of autoimmune diabetes. Transgenic expression of D6 in pancreatic islets of NOD mice reduced this pathogenic process by suppressing activation of autoreactive lymphocytes and by reducing migration of lymphocytes to the pancreas.

MMP-9 mRNA as a Therapeutic Marker in Acute and Chronic Stages of Arthritis Induced by Type II Collagen Antibody

BACKGROUND/PURPOSE Antibodies against type II collagen (anti-CII) are arthritogenic and central to the initiation of the disease. An animal model of collagen type II-specific monoclonal antibody-induced arthritis (CAIA) has been used for the evaluation of various therapeutic effects in rheumatoid arthritis (RA). We aimed to measure the expression of matrix metalloproteinase (MMP)-9 (gelatinase B), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in the acute and chronic stages of the CAIA model for application as a therapeutic marker. METHODS A commercially available antibody cocktail containing four monoclonal anti-type II collagen antibodies were injected into 6 to 8-week-old male BALB/c mice (n=20) and 50 microL lipopolysaccharide was injected 3 days later. The clinical manifestations of RA were recorded and scored at 10 days (acute stage) and 21 days (chronic stage). Then the mice were sacrificed for histologic analysis of the inflamed footpad and gene expression of IL-1beta, TNF-alpha and MMP-9 by ELISA and quantitative polymerase chain reaction amplification. RESULTS Marked inflammation was found in the limb joints of mice at 10 days. Both IL-1beta and MMP-9 expression played a central role in the inflammatory reaction in the acute stage. The expression level of MMP-9 mRNA remained high in the chronic stage of CAIA, but that of IL-1beta mRNA was unexpectedly negligible; the serum level of TNF-alpha in CAIA was undetectable in the acute stage. The expression level of TNF-alpha mRNA was also lower than IL-1beta and MMP-9 in the acute inflammatory stage. CONCLUSION The CAIA model is a fast and highly replicable model of RA. MMP-9 and IL-1beta were highly expressed in the acute stage of CAIA. It is suggested the MMP-9 mRNA level is a suitable marker for both acute and chronic stage, whereas IL-1beta is a marker only for the acute stage of the CAIA murine model.