A case of Castleman's disease complicated with nephrotic syndrome due to glomerulopathy mimicking membranoproliferative glomerulonephritis

Castleman's disease is a rare atypical lymphoproliferative disorder. Renal manifestations, such as proteinuria, hematuria, and renal dysfunction, are common in Castleman's disease; however, a nephrotic syndrome rarely occurs. We have encountered an unusual case of Castleman's disease of the plasma cell type characterized by nephrotic syndrome because of glomerulopathy mimicking membranoproliferative glomerulonephritis. Our patient showed higher levels of circulating cytokines (interleukin-6/vascular endothelial cell-derived growth factor), the glomerular lesions not associated with immunocomplex deposition, and the resolution of nephrotic syndrome after successful corticosteroids therapy resulting in a decline in cytokines levels, thereby implicating a cytokine-induced glomerular cell injury/activation as a possible cause of the glomerular pathological changes in this case.     

Effects of Cellulose Supplementation on Fecal Consistency and Fecal Weight

We investigated the effects of cellulose supplementation on fecal consistency and fecal weight. About 26 women were classified into two groups-normal defecation and constipation groups. All subjects ate the following meals during the experiment: ordinary meals (first week), experimental meals (second week), and experimental meals mixed with 4 g (third week) and 8 g (fourth week) cellulose. The experimental meal contained 16.7 g fiber. Fecal weights, fecal water content, fecal consistency, and defecation frequency were measured during the experimental period. As a result, in the normal defecation group, the mean fecal weight was 222.9 g day(-1) in the first week, and thereafter decreased. Although 20/24 g of fiber intake in the third/fourth week increased the fecal weight to over 150 g, the fecal consistency was still lower than the optimal consistency of around 300 g cm(-2). However, these changes were not observed in the constipated group.     

A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

Mirror visual feedback can induce motor learning in patients with callosal disconnection

Mirror therapy using mirror visual feedback (MVF) has been applied to the stroke rehabilitation of hemiparesis. One possible mechanism of mirror therapy is the functional interhemispheric connectivity between sensorimotor areas via corpus callosum. To test this hypothesis, we investigated the MVF-induced motor learning in 2 patients with callosal disconnection. Callosal connection in patients was evaluated by clinical measures and the interhemispheric inhibition (IHI) using transcranial magnetic stimulation. Both patients suffered from somatosensory cognitive disconnection, and one showed the loss of IHI. Motor training with MVF significantly improved the motor behavior of both patients. Extending our previous study, the results of callosal patients suggested that the visual feedback through a mirror might play the crucial important role for the improvement of motor performance, rather than interhemispheric interaction via corpus callosum.     

Molecular and immunological developments in placentas

Cytotrophoblasts differentiate in two directions during early placentation: syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). STBs face maternal immune cells in placentas, and EVTs, which invade the decidua and uterine myometrium, face the cells in the uterus. This situation, in which trophoblasts come into contact with maternal immune cells, is known as the maternal-fetal interface. Despite fetuses and fetus-derived trophoblast cells being of the semi-allogeneic conceptus, fetuses and placentas are not rejected by the maternal immune system because of maternal-fetal tolerance. The acquired tolerance develops during normal placentation, resulting in normal fetal development in humans. In this review, we introduce placental development from the viewpoint of molecular biology. In addition, we discuss how the disruption of placental development could lead to complications in pregnancy, such as hypertensive disorder of pregnancy, fetal growth restriction, or miscarriage.     

Evaluation of the relationship between linezolid exposure and hyponatremia

IntroductionAims of this study were (a) to assess the development ratio of hyponatremia during treatment with linezolid and (b) to evaluate the relationship between the risk of hyponatremia and linezolid exposure and patient background.MethodClinical data including linezolid serum concentrations and serum sodium values were collected at Toyama University Hospital and Kyorin University Hospital. Data from 89 patients were used for the analysis, and a nadir serum sodium level ≤130 mmol/L during the treatment with linezolid was defined as hyponatremia. Mann-Whitney's U test was used to evaluate the effects of the area under the time-concentration curve (AUC) of linezolid at the nadir sodium level, clinical characteristics (e.g. laboratory data), and baseline serum sodium levels on the development of hyponatremia.ResultsThe hyponatremia was occurred in 21 of 89 patients (23.6%). Data are compared for baseline and nadir serum sodium levels of patients with and without hyponatremia. In both groups, nadir serum sodium levels were significantly different from those of the baseline values (P < 0.05). The values of AUC_0-12, accumulated AUC, baseline serum sodium levels and age were significantly different between patients with and without hyponatremia (P < 0.05).ConclusionsLinezolid exposure, age, and baseline sodium levels were detected as the risk factors for linezolid-related hyponatremia. Our findings suggest that regular monitoring of serum sodium levels is desirable during treatment with linezolid, especially for the elderly and patients with low serum sodium levels before the start of linezolid administration.     

Analysis of risk factors for multidrug-resistant pathogens and appropriate treatment indications for pneumonia in children with neurologic impairment

IntroductionThe features of pneumonia in children with neurologic impairment (NI) resemble those of healthcare-associated pneumonia is defined as pneumonia occurring in the community associated with healthcare risk factors. There are currently no guidelines for the treatment of pneumonia in children with NI. Here, we assessed whether the guidelines applicable for treating pneumonia in adults could be applied to children with NI.MethodsBetween 2008 and 2019, we enrolled children with NI who developed pneumonia and were treated in the pediatric ward of Kawasaki Medical School Hospital. We evaluated patient characteristics, the frequency of isolation of multidrug-resistant (MDR) pathogens, and clinical outcomes.ResultsMDR pathogens were more frequently isolated from patients receiving tube feeding (TF) and/or with tracheostomy than from patients without these risk factors. Other risk factors, including a history of antibiotic therapy and methicillin-resistant Staphylococcus aureus isolation, recent hospitalization, residence in a nursing home or extended care facility, and low-dose, long-term macrolide therapy, did not significantly affect the frequency of MDR pathogen isolation. In patients receiving TF and/or with tracheostomy, treatment success was achieved in all cases treated with broad-spectrum antibiotics and 72.2% of cases treated with non-broad-spectrum antibiotics (P = 0.007). Conversely, among patients without these risk factors, no such difference was observed.ConclusionsOur findings indicate that the guideline to select antibiotics for treating pneumonia in children with NI should be simpler and more useful than the current guidelines for adult pneumonia, based on risk factor assessment for MDR pathogens.