Salt intake causes B-type natriuretic peptide elevation independently of blood pressure elevation in the general population without hypertension and heart disease

Excessive salt intake causes hypertension and cardiovascular diseases (CVDs). B-type natriuretic peptide (BNP) is synthesized and released from the ventricle, and is a surrogate marker reflecting various CVDs. Moreover, when a slight BNP elevation is shown, it leads to a poor prognosis in the general population. However, the relationship between salt intake and BNP levels in the general population remains unclear, especially in those without hypertension and heart diseases.In this study, we recruited 1404 participants without hypertension and electrocardiogram abnormalities, who received regular annual health check-ups in Japan. Plasma BNP levels were measured, and daily salt intake levels were evaluated using urinary samples. In addition, some clinical parameters were obtained, and the data were cross-sectionally analyzed.The median of plasma BNP levels was 10.50 pg/mL, and daily salt intake was 8.50 ± 1.85 g. When dividing participants into quartiles according to daily salt intake, those with the highest daily salt intake revealed the highest plasma BNP levels. Plasma BNP levels were significantly and positively associated with daily salt intake. Moreover, multiple linear regression analyses revealed that plasma BNP levels showed a significant positive association with daily salt intake levels after adjustments.Plasma BNP levels were significantly and positively associated with daily salt intake after adjustment in the general population. Plasma BNP levels may be a surrogate marker reflecting salt-induced heart diseases.     

Endoscopic transpapillary bile duct biopsy with the combination of intraductal ultrasonography in the diagnosis of biliary strictures

BACKGROUND: When endoscopic retrograde cholangiopancreatography (ERCP) guided bile duct biopsy fails to demonstrate malignancy, it remains unclear how to manage patients with presumably malignant strictures. AIMS: To evaluate the value of intraductal ultrasonography (IDUS) when bile duct biopsy is negative. METHODS: Sixty two patients with strictures of the bile duct were studied prospectively. During ERCP, IDUS was performed using an ultrasonic probe (diameter 2.0 mm; frequency 20 MHz). Following IDUS, a bile duct biopsy was performed using forceps (diameter 1.8 mm). The IDUS images of the tumour were classified as polypoid lesions, localised wall thickening, intraductal sessile tumours, sessile tumour outside of the bile duct, or absence of apparent lesion. The bile duct wall structures at the site of the tumour as well as the maximum diameter of the tumour were also analysed. The IDUS findings were compared with the histological findings or clinical course. RESULTS: When the IDUS images showed a polypoid lesion (n=19), localised wall thickening (n=8), intraductal sessile tumour (n=13), and sessile tumour outside of the bile duct (n = 20), the sensitivities of the biopsy were 80%, 50%, 92%, and 53%, respectively. Multiple regression analysis showed that the presence of sessile tumour (intraductal or outside of the bile duct: p<0.05), tumour size greater than 10.0 mm (p<0.001), and interrupted wall structure (p<0.05) were independent variables that predicted malignancy. CONCLUSION: When biopsy fails to demonstrate evidence of malignancy, the presence of sessile tumour (intraductal or outside of the bile duct), tumour size greater than 10.0 mm, and interrupted wall structure on IDUS images are factors that can predict malignancy.     

A case of endocapillary proliferative glomerulonephritis with macrophages phagocytosing monoclonal immunoglobulin lambda light chain

Multiple myeloma (MM) is a plasma‐cell neoplasm that can cause renal disorders. Renal lesions in MM can present with a very rare pathological manifestation involving a specific monoclonal immunoglobulin (Ig). We report the case of a 33‐year‐old woman who had edema, fatigue, elevated serum creatinine levels, hypoalbuminemia, and hypercholesterolemia. She had persistent hematuria and proteinuria lasting 3 years. Serum protein electrophoresis showed an M‐spike, and serum immunofixation demonstrated the presence of monoclonal IgG λ. She had proteinuria in the nephrotic range, and a monoclonal λ fragment was present on urine immunofixation. Renal biopsy showed proliferative glomerulonephritis with λ light chain and C3c deposition and inflammatory cell infiltration with CD68. Macrophage lysosomes contained λ light chains, suggesting their partial phagocytosis. She was diagnosed with symptomatic MM and was treated with bortezomib and dexamethasone and an autologous peripheral stem cell transplant conditioned with intravenous melphalan. She achieved a partial response with decreased serum monoclonal protein and improved renal function. This case may be categorized as a monoclonal gammopathy‐associated proliferative glomerulonephritis. The biopsy finding of partially phagocytosed Ig λ light chains by macrophages is very rare; this pathological condition is similar to crystal‐storing histiocytosis.     

Importance of standardization of hemoglobin A1c in the analysis of factors that predict hemoglobin A1c levels in non-diabetic residents of three distinct areas of Japan

We performed a statistical analysis to elucidate effects of standardized measurement of hemoglobin A1c (HbA1c) on analysis of factors that affect HbA1c values. Subjects were participants in the Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases, and a total of 1789 men and 3150 women in three distinct areas who did not have overt diabetes (HbA1c> or =6.1% or prior diagnosis) were analyzed. A different method of HbA1c assay was used in each area: high-performance liquid chromatography in one area and a different immunochemical method in each of the other two areas. Then, calibration of HbA1c was performed using two HbA1c standards (5.5 and 10.5%) provided by the Japan Diabetes Society. Analysis of co-variance was performed separately in men and women. When raw HbA1c data were used as the outcome, 'area', which represents differences in assay systems, lifestyles, etc. had a significant effect on HbA1c levels. When calibrated HbA1c data were used, however, 'area' was no longer a significant factor. In the latter analysis, age and BMI were the principal contributors to HbA1c, and parental history of diabetes had a weak effect in women. Thus, standardization of HbA1c reduced the difference between assay systems, and uncovered two common factors to determine HbA1c levels.     

Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.     

Cycling probe technology to quantify and discriminate between wild-type varicella-zoster virus and Oka vaccine strains

Rapid differentiation between wild-type varicella zoster virus (VZV) and Oka-vaccine (vOka) strains is important for monitoring side reactions of varicella vaccination. To develop a high-throughput molecular diagnostic method for the differentiation of wild-type VZV and vOka strains based on cycling probe technology. The primers were designed to amplify common sequences spanning a single nucleotide polymorphism (SNP) in gene 62 of VZV. DNA–RNA chimeric probes (cycling probes) were designed to detect the SNP at nucleotide 105705. The cycling probe real-time PCR assays for VZV wild-type and vOka strains specifically amplified plasmids containing target sequences that ranged between 10 and 1 × 10⁶ copies per reaction. The inter- and intra-assay coefficients of variation were less than 5%. After initial validation studies, the clinical reliability of this method was evaluated using 38 swab samples that were collected from patients suspected of being zoster. Compared to the loop mediated isothermal amplification method, which is defined as the gold standard, cycling probe real-time PCR was highly sensitive and specific. The cycling probe real-time PCR technology is a reliable tool for differentiating between wild-type VZV and vOka strains in clinical samples.     

Evaluation of Malignant Breast Lesions Using High-resolution Readout-segmented Diffusion-weighted Echo-planar Imaging: Comparison with Pathology

Purpose:We aimed to investigate the performance of high resolution-diffusion-weighted imaging (HR-DWI) using readout-segmented echo-planar imaging in visualizing malignant breast lesions and evaluating their extent, using pathology as a reference.Methods:This retrospective study included patients who underwent HR-DWI with surgically confirmed malignant breast lesions. Two radiologists blinded to the final diagnosis evaluated HR-DWI independently and identified the lesions, measuring their maximum diameters. Another radiologist confirmed if those lesions were identical to the pathology. The maximum diameters of the lesions between HR-DWI and pathology were compared, and their correlations were calculated using Spearman’s correlation coefficient. Apparent diffusion coefficient (ADC) values of the lesions were measured.Results:Ninety-five mass/64 non-mass lesions were pathologically confirmed in 104 females. Both radiologists detected the same 93 mass lesions (97.9%). Spearman’s correlation coefficient for mass lesions were 0.89 and 0.90 (P < 0.0001 and 0001) for the two radiologists, respectively. The size differences within 10 mm were 90.3% (84/93) and 94.6% (88/93) respectively. One radiologist detected 35 non-mass lesions (54.7%) and another radiologist detected 32 non-mass lesions (50.0%), of which 28 lesions were confirmed as identical. Spearman’s correlation coefficient for non-mass lesions were 0.59 and 0.22 (P = 0.0002 and 0.22), respectively. The mean ADC value of mass lesions and non-mass lesions were 0.80 and 0.89 × 10⁻³ mm²/s, respectively.Conclusion:Using HR-DWI, malignant mass lesions were depicted with excellent agreement with the pathological evaluation. Approximately half of the non-mass lesions could not be identified, suggesting a current limitation of HR-DWI.     

Peripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant

IntroductionAminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their correct tRNAs. Bi-allelic truncating variants in the AIMP1 gene have been associated with hypomyelinating leukodystrophy-3 (HLD3; MIM 260600), which is characterized by hypomyelination, microcephaly, seizures and decreased life expectancy. Although peripheral nerve involvement has been assumed for HLD3, no compelling evidence is available to date.Case reportThe case was a first-born Filipino male. He showed profound developmental delay, failure to thrive, and spasticity in his limbs. At three months of age he developed refractory epilepsy. Serial magnetic resonance imaging (MRIs) showed profound myelination delay and progressive cerebral atrophy. He showed abnormal nerve conduction studies. Genetic testing revealed a homozygous pathogenic variant in the AIMP1 gene (NM_004757.3: c.115C > T: p.Gln39*). The parents were heterozygous for the same variant.ConclusionHere, we report a patient with a homozygous nonsense AIMP1 variant showing peripheral neuropathy as well as HLD3. Our case suggests that AIMP1 plays a pivotal role in the peripheral nerve as well as the central nervous system.