Association of abnormalities in electrocardiography and ultrasonic echocardiography with the occurrence of cardiovascular disease in patients with advanced chronic kidney disease.

BACKGROUND: In patients with chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) increases with disease progression. CVD screening tests in those with CKD were researched to determine whether abnormalities observed in electrocardiography (ECG) and ultrasonic echocardiography (UCG) were risk factors associated with the development of CVD. METHODS: This study included 604 patients with CKD G4 and G5, for whom both ECG and UCG were performed. They were divided into four groups: those without ECG- and UCG-indicated abnormalities (group A, n = 333), with only ECG abnormalities (group B, n = 106), with only UCG abnormalities (group C, n = 75), and with both ECG and UCG abnormalities (group D, n = 90). Multivariate analysis using Cox regression analysis of the occurrence of CVD was performed during a follow-up period. RESULTS: During the observation period, 124 patients had clinical events. Among them, 45 patients (13.5%) were in Group A, 25 patients (23.6%) in Group B, 19 patients (25.3%) in Group C, and 35 patients (38.9%) in Group D, respectively. CVD event occurrence was highest in Group D. The results of the multivariate analysis also showed that the CVD event rates were significantly higher in Group C (HR: 2.96, P = < .001) and D (HR: 4.22, P < .001) than in Group A. CONCLUSION: In patients with advanced CKD, there was a significant correlation of ECG and UCG abnormalities with CVD events. Additionally, those having both types of abnormalities may have a higher risk of coronary artery disease than other groups.

Comparison of two protocols for steroid pulse therapy in patients with IgA nephropathy: a retrospective observational study.

BACKGROUND: Steroid pulse (SP) therapy is one of the immunosuppressive therapies for immunoglobulin A nephropathy (IgAN). Although there are various protocols of SP therapy in IgAN, the intermittent SP (ISP) and consecutive SP (CSP) protocols are prevalently performed in clinical settings. However, there is a lack of evidence of comparisons of the effects on IgAN between these two protocols. METHODS: A total of 189 patients with IgAN who had received SP therapy were included in this study. They were divided into two groups according to the SP protocols into the intermittent SP (ISP) or consecutive SP (CSP) group as follows: ISP; three-times SP therapy in alternate months, CSP; three-times SP therapy in three consecutive weeks. Kidney function, remission of urinary findings, and side effects of SP therapy were compared between the two groups. The observational period was 12 months after the initiation of SP therapy. RESULTS: There was no significant difference in kidney function between the two groups during the observational period. The remission rate of proteinuria and hematuria at 12 months also did not significantly differ between the two groups. Furthermore, even after the adjustment of clinical characteristics using propensity score matching, the remission rate of proteinuria and hematuria at 12 months was similar between the two groups. At 2 months, the remission rate of proteinuria was significantly higher in the CSP group than in the ISP group. There were no critical side effects in both groups. CONCLUSION: The effects of SP therapy on IgAN were similar between the ISP and CSP group at 12 months although CSP therapy could remit proteinuria faster than ISP therapy.

Changes in blood pressure during treatment with the tyrosine kinase inhibitor lenvatinib.

BACKGROUND: Within the class of tyrosine kinase inhibitors (TKIs), which are used for the treatment of numerous advanced cancers, lenvatinib is associated with a higher prevalence of hypertension (HT) compared with other TKIs. In this study, we investigated the effect of lenvatinib on blood pressure (BP) and associated factors. METHODS: This single-centre, retrospective observational study included 25 consecutive patients treated with lenvatinib for unresectable hepatocellular carcinoma from April 2018 to December 2018 at the study institution. We assessed changes in BP using ambulatory BP monitoring, urinary sodium excretion, kidney function, use of antihypertensive agents and diuretics, and fluid retention following treatment initiation with lenvatinib. RESULTS: At 1 week after treatment initiation, the mean BP and the percentage of patients with riser pattern significantly increased compared with those at the baseline. Although there were no significant changes at 1 week, urinary sodium excretion (153.4 ± 51.7 and 112.5 ± 65.0 mEq/day at 1 and 3 weeks, respectively, P < 0.05) and estimated glomerular filtration rate significantly decreased and the number of patients with fluid retention increased at 3 weeks. Furthermore, patients with fluid retention had significantly higher BP or required more intensive BP treatment compared with those without fluid retention. CONCLUSIONS: Lenvatinib might lead to HT without fluid retention soon after the initiation of treatment, subsequently leading to a reduction in urinary sodium excretion, thereby contributing to a rise in BP by fluid retention.

Prevalence of occupational allergy in medical researchers exposed to laboratory animals.

Allergy to laboratory animals is a well known occupational hazard and remains a health concern for individuals in contact with lab animals. This study evaluates the prevalence of allergy symptoms among medical researchers exposed to laboratory animals. We analyzed data from a cross-sectional survey, involving subjects (n=169, 21-59 yr), working in Kochi Medical School, Japan. They were asked to fill out a questionnaire to evaluate symptoms related to contact with laboratory animals. The overall response rate was 86.2%. The prevalence of laboratory animal allergy was 17.6%. The symptoms most reported were allergic rhino-conjunctivitis and asthma. A small number of the subjects received education on the allergy issue and 62.5% of subjects with an allergy to laboratory animals claimed to have atopy. Protection from animal allergens should be a high priority for institutions using lab animals; providing continuous education to animal handlers would be meaningful to reduce and control exposure.

Senescent case of cholesterol ester storage disease that progressed to liver cirrhosis with a novel mutation (N250H) of lysosomal acid lipase gene.

The patient, a 69-year-old man, had a chief complaint of hepatomegaly. The liver was palpated four fingerbreadths below the costal margin, and the spleen was three fingerbreadths below the costal margin. There were no other abnormal findings. Laparoscopy showed that the liver resembled an orange-yellow crayon in appearance and was nodular. The pathological findings of the liver biopsy tissue were consistent with liver cirrhosis. Inside the fibrous septum was an apparent aggregation of enlarged macrophages that phagocytosed lipid components, as well as enlarged Kupffer cells that phagocytosed lipid droplets. Electron microscopy showed the lipid droplets to have a moth-eaten appearance. Using monocytes extracted from the peripheral blood, acid lipase activity was measured by fluorescence spectrometry using 4-methylumbelliferone palmitate as a substrate. This patient's human lysosomal acid lipase activity was 0.020 nM/min per 10(6) cells, corresponding to 5.9% of that in healthy subjects (0.332 ± 0.066 nM/min per 10(6) cells). Cholesterol ester storage disease was therefore diagnosed. The acid lipase A base sequence obtained from leukocytes by direct sequencing was compared with a library. This patient had a point mutation of N250H/N250H in exon 7, a novel gene abnormality that has not previously been reported.

Patient with eight metachronous gastrointestinal cancers thought to be hereditary nonpolyposis colorectal cancer (HNPCC).

An 81-year-old woman presented with a chief complaint of swelling of both lower legs. She had a history of surgery for cancers of the stomach, rectum and colon. Among her immediate family members, her son had colon and rectal cancers, and her sister had ovarian cancer. After close examination the patient was diagnosed with small intestine cancer and ascending colon cancer. Gene mutation analyses did not reveal any mutations in DNA mismatch repair genes, but MSH-2 protein expression was lost only in the cancer lesions. Here, we report this rare case of eight metachronous gastrointestinal cancers thought to be HNPCC.

Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK.

It is generally believed that a mechanical signal initiates a cascade of biological events leading to coordinated cardiac remodeling. 14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. To evaluate the molecular mechanism underlying swimming stress-induced cardiac remodeling, we examined the role of 14-3-3 protein and MAPK pathway by pharmacological and genetic means using transgenic mice with cardiac-specific expression of dominant-negative (DN) mutants of 14-3-3 (DN 14-3-3/TG) and p38alpha/beta MAPK (DNp38alpha and DNp38beta) mice. p38 MAPK activation was earlier, more marked, and longer in the myocardium of the TG group compared with that of the nontransgenic (NTG) group after swimming stress, whereas JNK activation was detected on day 5 and decreased afterward. In contrast, ERK1/2 was not activated after swimming stress in either group. Cardiomyocyte apoptosis, cardiac hypertrophy, and fibrosis were greatly increased in the TG group compared with those in the NTG group. Moreover, we found a significant correlation between p38 MAPK activation and apoptosis in the TG group. Furthermore, DN 14-3-3 hearts showed enhanced atrial natriuretic peptide expression. In contrast, DNp38alpha and DNp38beta mice exhibited reduced mortality and increased resistance to cardiac remodeling after 28 days of swimming stress compared with TG and NTG mice. Besides, treatment with a p38 MAPK inhibitor, FR-167653, resulted in regression of cardiac hypertrophy and fibrosis and improvement in the survival rate in the TG group. These results indicate for the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in left ventricular remodeling associated with swimming stress.

Randomized controlled study of 3 different types of hemoclips for hemostasis of bleeding canine acute gastric ulcers.

BACKGROUND: Mechanical closure of bleeding vessels is clinically appealing, and several types of hemoclips are now marketed for endoscopic hemostasis of nonvariceal lesions. No comparative data have been reported on ease of clip placement, hemostasis efficacy, or clip retention rates on bleeding ulcers. OBJECTIVE: To compare 3 different types of hemoclips for hemostasis of bleeding ulcers. DESIGN: Randomized controlled study. SUBJECTS: Seven adult dogs with prehepatic portal hypertension were heparinized, and acute gastric ulcers were made with jumbo biopsy forceps. Animals had oral proton pump inhibitors daily and weekly endoscopies to quantitate clip retention and ulcer healing. INTERVENTIONS: Bleeding ulcers were randomized in pairs (2 for each treatment/dog) to endoscopic hemoclip treatment or control. MAIN OUTCOME MEASUREMENTS: Initial times and success of deployment, hemostasis efficacy, clip retention rates, and ulcer healing during endoscopic follow-ups. RESULTS: There was no difference in initial hemostasis rates of hemoclips, and no major complications occurred. Ulcer healing times were faster (Resolution Clip [RC] or TriClip [TC]) or similar (QuickClip2 [QC]) to controls. Clip retention at 1 week was significantly less with TC and, at 3 to 7 weeks, was significantly higher with RC. CONCLUSIONS: (1) For the 3 hemoclip devices, initial hemostasis rates were 100%, but all devices required similar learning time to place clips successfully. (2) Short-term retention rates of TC were significantly less than QC or RC. (3) Long-term clip retention was significantly higher with RC. (4) All 3 hemoclips were safe, and none interfered with ulcer healing.

Randomized double-blind studies of polysaccharide gel compared with glue and other agents for hemostasis of large veins and bleeding canine esophageal or gastric varices.

BACKGROUND: The safety and efficacy of poly-N-acetyl glucosamine (p-GlcNAc) gels were compared with standard agents in three different dog studies to assess abdominal venous collaterals, bleeding esophageal varices, and bleeding gastric varices. METHODS: Adult dogs with prehepatic portal hypertension and large abdominal venous collaterals, esophageal varices, or gastric varices were studied. RESULTS: Significantly higher sclerosis rates were seen with F2 or F4 p-GlcNAc gels and standard sclerosants. F2 and F4 gels had high rates of permanent hemostasis, low rates of secondary ulceration, and significant reductions in esophageal and gastric variceal size. These results were either equivalent to or significantly better than the most commonly used gastric varix hemostatic agent (glue) or other sclerosing agents. CONCLUSION: F2 and F4 poly-N-acetyl glucosamine gels are promising therapeutic agents for venous and variceal hemostasis.