Clinical application of artificial ligament for ankle instability--long-term follow-up

We have applied a reconstructive operation to patients with injury of the lateral ligament in the ankle joint using an artificial ligament made of polyester (Leeds-Keio) since 1985. The operation was performed on 451 feet of 436 patients. Average follow-up period was 5 years and 8 months. Talar tilt and anterior drawer translation before and after the operation were improved from 16 degrees to 4 degrees and from 11 mm to 4 mm, respectively. In this study, which has followed the same patients over an extended period, there were no cases with a decrease in the range of motion of the joint, with further development of osteoarthritis, or with a poorer result than those observed in our earlier study, which reported a short-term follow-up of the same patients. It may therefore be concluded that this reconstructive procedure of the lateral ligament of the ankle joint, using the artificial ligament, is also excellent after long-term follow-up.     

Predictability of tricuspid annular plane systolic excursion for the effectiveness of tolvaptan in patients with heart failure

Background

There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF.

Methods

This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan. Tolvaptan responders were defined as those having a body weight decrease from baseline >1 kg on the morning of day 8.

Results

The mean age of the 62 patients was 75.1 ± 13.9 years, and 45 patients (72.6%) were considered to be responders. Tricuspid annular plane systolic excursion (TAPSE) was significantly higher (17.1 ± 3.8 vs. 13.0 ± 3.9 mm; p = 0.0004) and the tricuspid valve regurgitation pressure gradient (33.3 ± 14.6 vs. 44.9 ± 12.2 mmHg; p = 0.007) and estimated right atrium pressure (7.8 ± 4.2 vs. 10.3 ± 4.5 mmHg; p = 0.043) were significantly lower in the Responder group than in the Non-responder group. In a multivariate logistic regression analysis, TAPSE was found to be an independent predictor of response (odds ratio 1.28; 95% confidence interval 1.03–1.60). According to the receiver operating characteristics analysis, the area under the curve of TAPSE was the largest among the parameters measured by echocardiography. The cut-off value for TAPSE to predict responders was determined to be 17.0 mm (sensitivity = 56.8%, specificity = 94.1%).

Conclusions

TAPSE is a simple predictor of the effectiveness of tolvaptan in patients with HF.

     

Multifunctional envelope-type nano device (MEND) as a non-viral gene delivery system

In this review, we describe a key role of octaarginine (R8) in developing our new concept of "Programmed Packaging", by which we succeeded in creating a multifunctional envelope-type nano device (MEND) as a non-viral gene-delivery system. This concept can be applied not only to nuclear targeting of plasmid DNA (pDNA) but also to cytosolic delivery of functional nucleic acids such as oligonucleotides or siRNA. This concept has been extended to other organelles such as mitochondria as a foundation for innovative nanomedicine. Finally, we discuss the rate-limiting step in gene delivery by comparing non-viral and viral gene delivery systems, which clearly indicates the importance of nuclear disposition of pDNA for efficient transfection.     

Comparative analysis of epidermal growth factor receptor mutations and gene amplification as predictors of gefitinib efficacy in Japanese patients with nonsmall cell lung cancer

BACKGROUND: Because the investigation of epidermal growth factor receptor gene (EGFR) status as a predictor of gefitinib efficacy in Japanese patients has shown promise, the authors evaluated EGFR mutations and gene amplification in biopsy specimens from Japanese patients with nonsmall cell lung cancer (NSCLC) who received treatment with gefitinib to analyze the correlation between EGFR gene status and clinical outcome. METHODS: Fifty-nine patients were enrolled in this study. EGFR gene amplification was evaluated by fluorescence in situ hybridization (FISH), and EGFR mutations in exons 18, 19, and 21 were analyzed by polymerase chain reaction and direct sequencing. RESULTS: EGFR mutations were detected in 17 patients (28.8%). FISH-positive results were observed in 26 patients (48.1%). The response rate was significantly higher in the patients with EGFR mutations than in the patients without mutations (58.8% vs 14.3%; P=.0005). No significant difference in the response rate was observed between FISH-positive patients and FISH-negative patients (31.8% vs 21.4%; P=.4339). EGFR mutation was correlated with both a longer time to progression (TTP) (7.3 months vs 1.8 months; P=.0030) and longer overall survival (OS) (18.9 months vs 6.4 months; P=.0092). No significant differences in TTP or OS were observed between FISH-positive patients andFISH-negative patients. The results from a multivariate analysis indicated that EGFR mutations maintained a significant association with longer TTP and longer OS. CONCLUSIONS: The results of this study suggested that EGFR mutations may serve as predictors of response and survival and that the role of EGFR gene amplification is not a predictor of gefitinib efficacy in Japanese patients with NSCLC.     

Acute lymphoblastic leukemia in a pediatric patient with Marfan's syndrome

We report a rare case of acute lymphoblastic leukemia (ALL) in a 7-year-old boy with Marfan's syndrome. He was diagnosed as having Marfan's syndrome by clinical findings at the age of 2 years, and the diagnosis was confirmed by the detection of gene mutation in FBN1. He was referred to our hospital because of the swelling of cervical lymph nodes at the age of 7 years. Findings on bone marrow examination demonstrated T lymphoblastic ALL. He obtained complete remission after induction therapy, and had no serious side effects including cardiotoxicity during chemotherapy. He has remained in continuous complete remission for 34 months following diagnosis. To our knowledge, only three cases of leukemia in patients with Marfan's syndrome were reported previously. We speculate that increased activity of TGF-β, which is known as a tumor suppressor factor, in patients with Marfan's syndrome may diminish the risk of developing leukemia, although such a thesis was not proven in this case.     

Posterior reversible encephalopathy syndrome mimicking subacute ischemic stroke: a case report

Posterior reversible encephalopathy syndrome, an acute onset neurological syndrome, is among the conditions that must be differentiated from stroke. Herein, we report a rare case of posterior reversible encephalopathy syndrome mimicking subacute ischemic stroke. A 68-year-old man was transferred by ambulance to our hospital because of visual disturbance. He showed left homonymous hemianopsia. Magnetic resonance imaging (diffusion-weighted imaging and fluid-attenuated inversion recovery imaging) revealed high signal intensity in the right occipital lobe. We suspected subacute cerebral infarction. After admission, he developed cortical blindness and increased blood pressure. Fluid-attenuated inversion recovery imaging revealed high signal intensity and elevated apparent diffusion coefficient values in the bilateral occipital lobes. We diagnosed the patient with posterior reversible encephalopathy syndrome. Antihypertensive treatment improved his clinical symptoms. Careful imaging assessment, including of changes over time, is important for diagnosing posterior reversible encephalopathy syndrome.