Current state and effectiveness of abdominal ultrasonography in complete medical screening

Purpose The current state and effectiveness of abdominal ultrasonography (US) were investigated by reviewing statistical data for US of the kidney as part of complete medical screenings conducted at our institution between April 1994 and March 2004. Methods Among 4339 individuals with US findings, computed tomography (CT) was performed on 129 individuals at our institution. Among these individuals, US findings and CT diagnoses were compared and analyzed. Results US findings indicated renal tumors in 73 of the 129 subjects, and the breakdown of CT diagnoses for these 73 individuals was as follows: no lesion, n = 45 (61.6%); simple renal cyst, n = 13 (17.8%); complicated renal cyst, n = 5 (6.8%); suspected malignant tumor, n = 5 (6.8%); renal angiomyolipoma, n = 2 (2.7%); pelvic dilatation, n = 1 (1.4%); granuloma, n = 1 (1.4%); teratoma, n = 1 (1.4%). Magnetic resonance imaging (MRI) was performed on 4 of the 5 subjects with suspected malignant tumor, and surgery was performed in all 4 cases with suspected kidney cancer. Kidney cancer was histopathologically confirmed in 2 patients, resulting in a detection rate of 0.046% for kidney cancer by US as part of a complete medical screening. In the 2 patients with kidney cancer, differentiating cystic renal cell cancer from a renal cyst was not possible based on US findings alone in 1 patient, and no thorough examinations were performed in the 3 years leading up to surgery. Conclusions These results suggest that additional US and thorough examinations are necessary if a lesion cannot be confirmed as a simple renal cyst on initial US. Furthermore, to improve the skill levels of healthcare professionals who perform and interpret US, a feedback system should be established where data related to complete medical screenings are available to the personnel involved.     

Acute oral selenium intoxication with ten times the lethal dose resulting in deep gastric ulcer

A 48-year-old woman presented after taking 2000 mg of selenium dioxide, corresponding to 10 times the experimental lethal dose in animals. She presented with mildly altered consciousness and hematemesis. Endoscopy revealed mucosal damage throughout the oral cavity, esophagus, and stomach. There was no evidence of perforation. After intubation and gastric lavage, hemodialysis was performed. The patient was discharged uneventfully on the 16(th) day. This case highlights a very rare acute selenium intoxication. Serum and urinary selenium levels and serum glutathione peroxidase activities during the patient's course were followed, as well as the mucosal corrosive damage caused by the selenium.     

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy

Background

The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis.

Methods

The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy.

Results

The median observation period was 70.4 (IQR 20.9–101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m²/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%.

Conclusions

This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

     

The prevalence of scapular malalignment in elementally school aged baseball player and its association to shoulder disorder

Background

Various shoulder disorders have been reported to be associated with scapulothoracic joint dysfunction in adult overhead athletes. However, little is known about the prevalence of scapular malalignment and its relationship to shoulder injuries in skeletally immature baseball players.The purpose of the current study was to investigate the prevalence of scapular malalignment in elementary school-aged baseball players, as well as its association with shoulder disorder.

Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline–alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na⁺-Cl⁻ cotransporter (NCC) and Na⁺-K⁺-2Cl⁻ cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.e., NaCl diuresis and vasodilation). In this study, we developed a new ELISA-based screening system to find novel SPAK inhibitors and screened >20,000 small-molecule compounds. Furthermore, we used a drug repositioning strategy to identify existing drugs that inhibit SPAK activity. As a result, we discovered one small-molecule compound (Stock 1S-14279) and an antiparasitic agent (Closantel) that inhibited SPAK-regulated phosphorylation and activation of NCC and NKCC1 in vitro and in mice. Notably, these compounds had structural similarity and inhibited SPAK in an ATP-insensitive manner. We propose that the two compounds found in this study may have great potential as novel antihypertensive drugs.