Doyeun Kim

Simultaneous mobile- and fixed-bearing total knee replacement in the same patients: A PROSPECTIVE COMPARISON OF MID-TERM OUTCOMES USING A SIMILAR DESIGN OF PROSTHESIS

We conducted a randomised prospective study to evaluate the clinical and radiological results of a mobile- and fixed-bearing total knee replacement of similar design in 174 patients who had bilateral simultaneous knee replacement. The mean follow-up was for 5.6 years (5.2 to 6.1). The total knee score, pain score, functional score and range of movement were not statistically different (p > 0.05) between the two groups. Osteolysis was not seen in any knee in either group. Two knees (1%) in the mobile-bearing group required revision because of infection; none in the fixed-bearing group needed revision. Excellent results can be achieved with both mobile- and fixed-bearing prostheses of similar design at mid-term follow-up. We could demonstrate no significant clinical advantage for a mobile bearing.

Clinical outcome and rate of complications after primary total knee replacement performed with quadriceps-sparing or standard arthrotomy

We performed a prospective, randomised study to compare the results and rates of complications of primary total knee replacement performed using a quadriceps-sparing technique or a standard arthrotomy in 120 patients who had bilateral total knee replacements carried out under the same anaesthetic. The clinical results, pain scales, surgical and hospital data, post-operative complications and radiological results were compared. No significant differences were found between the two groups with respect to the blood loss, knee score, function score, pain scale, range of movement or radiological findings. In contrast, the operating time (p = 0.0001) and the tourniquet time (p < 0.0001) were significantly longer in the quadriceps-sparing group, as was the rate of complications (p = 0.0468). We therefore recommend the use of a standard arthrotomy with the shortest possible skin incision for total knee replacement.

Protective effects of extracellular glutathione against Zn2+‐induced cell death in vitro and in vivo

The central nervous system reserves high concentrations of free Zn2+ in certain excitatory synaptic vesicles. In pathological conditions such as transient cerebral ischemia, traumatic brain injury, and kainic acid (KA)‐induced seizure, free Zn2+ is released in excess at synapses, which causes neuronal and glial death. We report here that glutathione (GSH) can be used as an effective means for protection of neural cells from Zn2+‐induced cell death in vitro and in vivo. Chronic treatment with 35 μM Zn2+ led to death of primary cortical neurons and primary astrocytes. The Zn2+ toxicity of cortical neurons was partially protected by 1 mM of GSH, whereas the Zn2+ toxicity of primary astrocyte cultures was blocked completely by 100 μM of GSH. To evaluate the beneficial effects of GSH in vivo, an excitotoxin‐induced neural cell death model was established by intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 μg) KA, which produced selective neuronal death, especially in CA1 and CA3 hippocampal regions. The i.c.v. co‐injection of 200 pmol of GSH significantly attenuated KA‐induced neuronal cell death and reactive gliosis in hippocampus. The results of this study suggest the contribution of Zn2+ in the excitotoxin‐induced neural cell death model and a potential value of GSH as a therapeutic means against Zn2+‐induced pathogenesis in brain.

Repression of phospho-JNK and infarct volume in ischemic brain of JIP1-deficient mice

Mice lacking JIP1, a scaffold protein that organizes JNK pathway components, were constructed independently by two groups. The proposed in vivo function, however, remains contradictory; One study reported that targeted disruption of the jip1 caused embryonic death due to the requirement of JIP1 for fertilized eggs (Thompson et al. [2001] J. Biol. Chem. 276:27745–27748). In contrast, another group (Whitmarsh et al. [2001] Genes Dev. 15:2421–2432) demonstrated that JIP1‐deficient mice were viable and that the JIP1 null mutation inhibited the kainic acid‐induced JNK activation and neuronal death. The current study was undertaken to re‐elucidate the in vivo roles of JIP1 using newly generated JIP1 knockout mice. Our JIP1‐deficient mice were viable and healthy. The transient focal ischemic insult produced by middle cerebral artery occlusion (MCAO) strongly activated JNK in brain of jip1+/+, jip1+/−, and jip1−/− mice. Increased JNK activity was sustained for more than 22 hr in jip1+/+ and jip1+/−, whereas it was repressed rapidly in jip1−/−. Concomitantly, the infarct volume produced by the ischemic insult in jip1−/− was reduced notably compared to that in jip1+/+ brain. These results suggest that JIP1 plays a pivotal role in regulating the maintenance of phosphorylated JNK and neuronal survival in postischemic brain, but is not essential for JNK activation and early development.

Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors

PURPOSE Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features. MATERIALS AND METHODS We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression. RESULTS The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression. CONCLUSION This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.