Improvement of endothelial function in parallel with the amelioration of dry cough and dyspnea due to interstitial pneumonia by intravenous cyclophosphamide pulse therapy in patients with systemic sclerosis: a preliminary report of two cases

Intravenous cyclophosphamide pulse therapy (IVCY) exerts its efficacy against interstitial lung disease (ILD) associated with systemic sclerosis (SSc) by restoring vascular injuries as well as aberrant immune activation. We recently experienced two patients with SSc-ILD in whom the values of brachial flow-mediated dilation (FMD) reflected the efficacy of IVCY. We herein report the details of these cases and discuss the potential of FMD to predict and evaluate the effect of IVCY on SSc-ILD.     

Usefulness of perflubutane microbubble-enhanced ultrasound in imaging and detection of prostate cancer: phase II multicenter clinical trial

Purpose

To explore the possibility of targeted biopsy (TBx) using transrectal ultrasound (US) with perflubutane microbubbles, we studied the findings of different cancerous tissue imaging modalities and evaluated needle biopsy in prostate cancer (PCa) using contrast-enhanced US (CEUS) in a multicenter clinical trial.

Methods

Seventy-one patients undergoing prostate biopsy received intravenous injection of perflubutane microbubbles (Sonazoid^®). We evaluated and compared images obtained by CEUS. The safety observation period was 2 days after contrast administration.

Results

Among the 30 patients with cancer, one or more sites with findings suggestive of cancer in CEUS were detected in 23 patients (32.4%) by TBx. Although 22 patients had positive cores of cancer by systematic biopsy (SBx), 8 patients had positive cores of cancer in TBx alone (11.3%). There was a significant difference in cancer detection rate by TBx between two cohorts with PSA < 10 ng/mL (22.9%) and PSA ≥ 10 ng/mL (52.2%) (P < 0.02). Close observation of various CEUS findings with Sonazoid^® enabled targeting of cancerous areas, and consequently, a significant difference (P < 0.05) in the detection rate of cancer was recognized in the transition zone (TZ): SBx; 21/120 (17.5%) and TBx; 17/55 (30.9%). The incidence of adverse events was 6.7% and that of adverse reactions was 4%.

Conclusions

CEUS with Sonazoid^® improved the detection rate of PCa by visualizing cancerous lesions. More detailed examination of CEUS images provided efficient characterization especially in the TZ area. TBx according to this procedure is expected to enable a lower number of biopsies and more accurate diagnosis of PCa.     

ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis

The diagnosis of amyotrophic lateral sclerosis (ALS) is difficult due to lack of definitive biomarkers. Our aim was to identify characteristic serum protein patterns that could provide candidate biomarkers for ALS. We divided mutant superoxide dismutase-1 (SOD1)^H46R rats into three groups based on disease progression: pre-symptom (90 days), onset, and end-stage. After separation of serum proteins using two-dimensional electrophoresis, we selected clear protein spots and identified two candidate proteins—inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) and glutathione peroxidase 3 (Gpx3). The 120 kDa ITIH4 increased at the onset of the disease and the 85 kDa ITIH4, a cleaved form, at the end-stage in the sera of the SOD1^H46R rats. Expression of the 85 kDa ITIH4 was substantial in ALS compared with controls or patients with muscular dystrophy, Alzheimer diseases, or Parkinson diseases. The Gpx3 protein levels in the sera of SOD1^H46R rats were upregulated pre-symptom and gradually decreased as the disease progressed. The Gpx3 protein levels were lower in the sera of the patients with ALS than in other diseases. These results indicate that ITIH4 and Gpx3 are potential biomarkers for ALS.     

Alexander disease with mild dorsal brainstem atrophy and infantile spasms

We present the case of a Japanese male infant with Alexander disease who developed infantile spasms at 8 months of age. The patient had a cluster of partial seizures at 4 months of age. He presented with mild general hypotonia and developmental delay. Macrocephaly was not observed. Brain magnetic resonance imaging (MRI) findings fulfilled all MRI-based criteria for the diagnosis of Alexander disease and revealed mild atrophy of the dorsal pons and medulla oblongata with abnormal intensities. DNA analysis disclosed a novel heterozygous missense mutation (c.1154 C>T, p.S385F) in the glial fibrillary acidic protein gene. At 8 months of age, tonic spasms occurred, and electroencephalography (EEG) revealed hypsarrhythmia. Lamotrigine effectively controlled the infantile spasms and improved the abnormal EEG findings. Although most patients with infantile Alexander disease have epilepsy, infantile spasms are rare. This comorbid condition may be associated with the distribution of the brain lesions and the age at onset of Alexander disease.     

Increased expression and activation of cathepsin K in human osteoarthritic cartilage and synovial tissues

Few studies have analyzed Cathepsin K (CatK) expression in human osteoarthritic tissues. We investigated CatK expression and activation in human articular cartilage using clinical specimens. Human osteoarthritic cartilage was obtained during surgery of total hip arthroplasty (n = 10), and control cartilage was from that of femoral head replacement for femoral neck fracture (n = 10). CatB, CatK, CatL, CatS, and Cystatin C (CysC) expressions were evaluated immunohistochemically and by real‐time PCR. Intracellular CatK protein was quantified by ELISA. Intracellular CatK activity was also investigated. Osteoarthritis (OA) chondrocytes were strongly stained with CatK, particularly in the superficial layer and more damaged areas. CatB, CatL, CatS, and CysC were weakly stained. CatK mRNA expression was significantly higher in OA group compared to that in control group (p = 0.043), whereas those of CatB, CatL, CatS, and CysC did not differ significantly. Mean CatK concentration (4.83 pmol/g protein) in OA chondrocytes was higher than that (3.91 pmol/g protein) in control chondrocytes (p = 0.001). CatK was enzymatically more activated in OA chondrocytes as compared with control chondrocytes. This study, for the first time, revealed increased CatK expression and activation in human OA cartilage, suggesting possible crucial roles for it in the pathogenesis of osteoarthritic change in articular cartilage. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:127–134, 2016.     

Quantitative in vivo biocompatibility of new ultralow‐nickel cobalt–chromium–molybdenum alloys

Nickel (Ni) eluted from metallic biomaterials is widely accepted as a major cause of allergies and inflammation. To improve the safety of cobalt–chromium–molybdenum (Co–Cr–Mo) alloy implants, new ultralow‐Ni Co–Cr–Mo alloys with and without zirconium (Zr) have been developed, with Ni contents of less than 0.01%. In the present study, we investigated the biocompatibility of these new alloys in vivo by subcutaneously implanting pure Ni, conventional Co–Cr–Mo, ultralow‐Ni Co–Cr–Mo, and ultralow‐Ni Co–Cr–Mo with Zr wires into the dorsal sides of mice. After 3 and 7 days, tissues around the wire were excised, and inflammation; the expression of IL‐1β, IL‐6, and TNF‐α; and Ni, Co, Cr, and Mo ion release were analyzed using histological analyses, qRT‐PCR, and inductively coupled plasma mass spectrometry (ICP‐MS), respectively. Significantly larger amounts of Ni eluted from pure Ni wires than from the other wires, and the degree of inflammation depended on the amount of eluted Ni. Although no significant differences in inflammatory reactions were identified among new alloys and conventional Co–Cr–Mo alloys in histological and qRT‐PCR analyses, ICP‐MS analysis revealed that Ni ion elution from ultralow‐Ni Co–Cr–Mo alloys with and without Zr was significantly lower than from conventional Co–Cr–Mo alloys. Our study, suggests that the present ultralow‐Ni Co–Cr–Mo alloys with and without Zr have greater safety and utility than conventional Co–Cr–Mo alloys. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1505–1513, 2016.