Incidence of steroid-associated osteonecrosis of the talus: a prospective MRI study

Objective

The purpose of this study was to determine the incidence of steroid-associated osteonecrosis (ON) of the talus in systemic lupus erythematosus (SLE) patients using a prospective magnetic resonance imaging (MRI) study.

Methods

We prospectively evaluated 110 SLE patients (220 tali) who required corticosteroid therapy using MRI. The incidence of ON of the talus was compared with the incidence of ON of the femoral head. We also divided these patients into two groups: those with and without ON of the talus. We compared these groups for gender differences, ages at initial corticosteroid therapy, and highest daily corticosteroid dosages.

Results

The incidence of ON of the talus was significantly lower than the incidence of ON of the femoral head (7.3 versus 49.5 %; p?<?0.001). No significant differences for gender, age at initial corticosteroid therapy, or highest daily corticosteroid dosage were observed between patients with and without ON of the talus. The rate of ON of the bilateral femoral head was significantly higher in those with ON of the talus than in those without ON of the talus.

Conclusion

Our results revealed that the incidence of ON of the talus was significantly lower than the incidence of ON of the femoral head.     

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.     

Histological analysis of arteriovenous anastomosis-like vessels established in the corpus luteum of cows during luteolysis

Background

The mechanisms regulating the function and regression of the corpus luteum (CL) have not yet been elucidated in detail. The regressed CL of cows was previously reported to be filled with unusual vessels like arteriovenous anastomosis (AVA); however how these vessels are being established during luteolysis remains unknown.

Methods

The bovine CL at different luteal stages and regressing bovine CL induced by prostaglandin F_2α (PGF) were histologically analyzed using light and electron microscopic levels. The changes in mRNA expression of genes encoding α-smooth muscle actin (SMA; Acta2) and transforming growth factor β1 (Tgfb1) in luteal tissues were analyzed by quantitative RT-PCR.

Results

AVA-like vessels appeared in the regressed CL with a diameter less than 1.5 cm in which no functional luteal cells and macrophages were observed. Epithelioid cells in the AVA-like vessel wall were immunoreactive for SMA, and the lumen of the vessels were narrow. Immunoreaction for SMA was found in the tunica media of typical arteries and arterioles, and pericytes around capillary vessel. Cells with elongated cytoplasmic processes ―resident fibroblasts expressing vimentin― distributed in the CL parenchyma without any association with blood vessels are also immunoreactive for SMA, and accumulated around arteries and arterioles during the late-luteal stage. In the regressed CL, walls of arteries and arterioles consisted of more than two layers of epithelioid cells positive for both SMA and desmin, suggesting that they are myofibroblasts transformed from fibroblasts. The percentage of the area positive for SMA and the mRNA expression of Acta2 were significantly increased in the regressed CL; however, they did not alter when a luteolytic dose of PGF was injected in vivo and collected within 24 h after the injection. On the other hand, Tgfb1, a known regulator for myofibroblast transformation, was significantly increased in PGF-induced regressing CL as well as in the CL during the late-luteal stage.

Conclusions

SMA-positive myofibroblasts accumulates around the arteries and arterioles to form AVA-like vessels during luteolysis in cows. PGF indirectly regulates myofibroblast transformation through enhancing the expression of TGFβ1. These peculiar AVA-like vessels may be involved in the regulation of blood flow in the bovine CL during luteolysis.

     

Hypertension and metabolic syndrome/lifestyle diseases

Hypertension is caused by metabolic syndrome. The primary cause of hypertension, however, is excess salt intake and an impaired renal salt excretory mechanism of the tubuloglomerular feedback mechanism involved in macula densa. Salt-losing nephropathy such as Gitelman's syndrome (which is caused by loss of function mutation in the tyhiazide-sensitive Na-Cl transporter, NCCT gene) is lacking in hypertension and has fewer cardiovascular complications despite the presence of the stimulated rennin-angiotensin-aldosterone system. It has been reported that an NCCT gene mutation is closely associated with diabetic nephropathy, suggesting an important role of NaCl metabolism in diabetic nephropathy. Loss of function of peroxisome proliferator-activated receptor(PPAR) -gamma(one of the key molecules of insulin resistance) has been shown to lead to obesity, diabetes and hypertension, suggesting a common basic background of such diseases. High insulin levels observed in insulin resistance would stimulate salt reabsorption in renal tubules, which may result in high blood pressure. Adipocytokines such as adiponectin, leptin and angiotensinogen may play some roles in metabolic syndrome. Taken together, good understanding of salt intake and its related factors in renal salt metabolism involved in metabolic syndrome will suppress further progression of atherosclerotic changes including chronic kidney disease.     

Rutaecarpine attenuates osteoclastogenesis by impairing macrophage colony stimulating factor and receptor activator of nuclear factor κ‐B ligand‐stimulated signalling pathways

Rutaecarpine is a major alkaloid isolated from Evodia rutaecarpa. Here, we investigated the effects of rutaecarpine on osteoclast differentiation induced by macrophage colony stimulating factor (M‐CSF) and receptor activator of nuclear factor κ‐B ligand (RANKL) in bone marrow‐derived macrophages (BMMs). Treatment with rutaecarpine significantly inhibited osteoclastogenesis and prevented bone resorption of BMM‐derived osteoclasts. Mechanistically, rutaecarpine decreased the protein level of nuclear factor of activated T cells cytoplasmic‐1 (NFATc1) and the phosphorylation of other signalling pathways during the osteoclast differentiation. Thus, rutaecarpine may be useful as a therapeutic agent for the treatment of bone diseases.     

A new evaluation method for upper extremity dexterity of patients with hemiparesis after stroke: the 10-second tests

We developed a new, sensitive evaluation method for upper extremity dexterity in patients with hemiparesis after stroke. This evaluation method consists of three types of test: the Finger Individual Movement Test, Hand Pronation and Supination Test, and Finger Tapping Test. In each test, the number of movements that can be performed during a 10-s period is measured. Data obtained by these 10-s tests were compared with those obtained by the Nine-Hole Peg Test (NHPT), and the usefulness of this new method was evaluated. In patients with hemiparesis after stroke, three types of 10-s test and NHPT were performed for the upper extremities on both the affected and unaffected sides. Simple correlation analysis and multiple regression analysis of data obtained by the three types of test and NHPT were performed using the affected/unaffected ratios. Twenty patients participated (54-85 years; 0.23-43.83 months after stroke) with mild upper extremity hemiparesis. Significant correlations exist between Finger Individual Movement Test and NHPT data (r=-0.584, P=0.0068) and between Hand Pronation and Supination Test and NHPT data (r=-0.707, P=0.0005). The multiple regression analysis model using the three types of 10-s test as explanatory variables was significant (P=0.0025) and explained 52.4% of the NHPT results. A significant association was observed between NHPT and the 10-s tests. The 10-s tests require no special examination instruments and can be readily performed in a short period. This evaluation method consisting of the 10-s tests can be a new clinical parameter of dexterity in patients with hemiparesis after stroke.     

Initial pulmonary metastasis after pancreatectomy for pancreatic ductal adenocarcinoma

Patients who undergo pancreatectomy for pancreatic ductal adenocarcinoma (PDA) develop relatively early recurrence, but pulmonary metastasis from PDA is rare. Between January 2008 and December 2016, a total of 120 consecutive patients underwent pancreatectomy for primary PDA at Osaka Medical College Hospital. Among these, 13 patients developed pulmonary metastasis and 6 patients underwent pulmonary metastasectomy. Among these patients, the median disease-free survival following initial pancreatic surgery was 26.1 months, and the median overall survival (OS) interval was 39 months. On the other hand, seven patients did not undergo pulmonary resection. The median OS interval of these patients was 33 months. The 1-, 3-, and 5-year OS rates were 100%, 80%, and 60%, respectively, for patients who underwent pulmonary metastasectomy and 100.0%, 42.8%, and 0%, respectively, for those who did not undergo the procedure. Our experience has shown that surgical resection may lengthen the survival time of patients who tolerate surgery.     

Fluorescence Detection of Malignant Liver Tumors using 5-Aminolevulinic Acid-Mediated Photodynamic Diagnosis: Principles,Technique, and Clinical Experience

Background

Photoactive drugs selectively accumulate in malignant tissue specimens and cause drug-induced fluorescence. Photodynamic diagnosis (PDD) and fluorescence can distinguish normal from malignant tissue.

Objective

Methods

From May 2012 to September 2013, a total of 70 patients underwent hepatic resections using 5-ALA-mediated PDD for liver tumors at our hospital.

Results

5-ALA fluorescence was detected in all hepatocellular carcinoma cases with serosa invasion. In liver metastasis from colorectal cancer cases with serosa invasion, 18 patients (85.7 %) were detected, and three patients (14.2 %) whose tumors showed complete response to neoadjuvant chemotherapy showed no fluorescence. Both superficial and deep malignant liver tumors were detected with 92.5 % sensitivity. Using 5-ALA-mediated PDD, tumors remaining at the cut surface and postoperative bile leakage were less frequent than in our previous hepatic resections using conventional white-light observation. Moreover, all malignant liver tumors were completely removed with a clear microscopic margin using 5-ALA, with a significant difference in resection margin width between 5-ALA-mediated PDD (6.7 ± 6.9 mm) and white-light observation (9.2 ± 7.0 mm; p = 0.0083).

Conclusions

With the detection of malignant liver tumors, residual tumor and bile leakage at the cut surface of the remnant liver were improved by PDD with 5-ALA. This procedure may provide greater sensitivity than the conventional procedure. Furthermore, 5-ALA-mediated PDD can ensure histological clearance regardless of the resection margin and preserve as much liver parenchyma as possible in patients with impaired liver function.