No child should suffer from vitamin K deficiency‐induced bleeding disorders

We encountered an 11‐day‐old male neonate with vitamin K deficiency‐induced intracranial hemorrhage, despite receiving oral vitamin K₂ (menaquinone‐4) prophylaxis according to Japanese guidelines. This case suggests that the current vitamin K deficiency‐bleeding prophylaxis programs cannot prevent bleeding completely. Better prophylaxis programs using both intramuscular and oral administration should be considered.     

Spinal cord stimulation for the treatment of pain and toe ulceration associated with systemic sclerosis: a case report

Systemic sclerosis is a complex disease characterized by extensive fibrosis, microvascular alterations, and additional sequelae. Microvascular alterations can cause painful ulcers and necrosis; however, conservative or surgical treatment is often challenging in terms of healing. The study aimed to describe a toe ulcer with systemic sclerosis and its’ successful treatment with spinal cord stimulation. An 83-year-old woman, who was diagnosed with systemic sclerosis over the past decade, was distressed by a non-healing toe ulcer for an extended period of time. The patient underwent spinal cord stimulation treatment with the expectation of pain relief and an improvement in microcirculatory insufficiency. Her pain scales and microcirculation improved, and the toe ulcer healed. Furthermore, the frequency of Raynaud’s symptoms was reduced, and the patient’s pain decreased. There was no recurrence of the ulcer and she no longer needed a cane for walking.     

Rhabdomyolysis Caused by Gefitinib Overdose

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are common therapeutic agents for EGFR mutation-positive advanced non-small-cell lung cancer. There has been no report of rhabdomyolysis caused by an overdose of EGFR-TKIs. We herein review the existing literature on the subject and report a rare case of rhabdomyolysis due to an overdose of gefitinib, an EGFR-TKI.     

Quantitative Evaluations of Posterior Staphylomas in Highly Myopic Eyes by Ultra-Widefield Optical Coherence Tomography

PurposeTo determine the shape of posterior staphylomas using ultra-widefield optical coherence tomographic (UWF-OCT) images and to identify the factors contributing to the shape and grade of the staphylomas in eyes with pathologic myopia.MethodsThis was an observational case series study. Highly myopic patients who were ≥40 years old with wide or narrow type of macular staphylomas were studied. High myopia was defined as a myopic refractive error (spherical equivalent) greater than −8.0 diopters (D) or an axial length (AL) > 26.5 mm. The maximum diameter and depth of the staphylomas were measured in the 12 radial scans of UWF-OCT images by ImageJ software and were compared between the two types of staphylomas.ResultsWe studied 197 eyes of 138 patients with a mean age of 64.7 ± 10.4 years and mean AL of 30.0 ± 1.9 mm. The AL was significantly longer in the eyes with the narrow type than the wide type of staphyloma (P = 0.036). Multiple regression analyses showed that age was significantly correlated with the maximum depth/maximum diameter ratio (wide type, P < 0.001; narrow type, P = 0.003) of both types of staphylomas. The AL was significantly correlated with the depth/diameter ratio of only the narrow type of staphylomas (P = 0.005).ConclusionsThe significant correlations of age and AL with the wide and narrow types of posterior staphylomas indicate that the factors for their formations may be distinctly different. Quantitative analyses of UWF-OCT images are helpful in determining the shape of the staphylomas.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

The effect of temperature on the mechanical aspects of rigor mortis in a liquid paraffin model

Rigor mortis is an important phenomenon to estimate the postmortem interval in forensic medicine. Rigor mortis is affected by temperature. We measured stiffness of rat muscles using a liquid paraffin model to monitor the mechanical aspects of rigor mortis at five temperatures (37, 25, 10, 5 and 0 °C). At 37, 25 and 10 °C, the progression of stiffness was slower in cooler conditions. At 5 and 0 °C, the muscle stiffness increased immediately after the muscles were soaked in cooled liquid paraffin and then muscles gradually became rigid without going through a relaxed state. This phenomenon suggests that it is important to be careful when estimating the postmortem interval in cold seasons.     

Experimental study of renal disorder caused by oxaliplatin in rat renal cortical slices

Background Oxaliplatin is a newly developed antitumor platinum complex that is known to have low nephrotoxicity. The inhibitory effects of oxaliplatin on several tubular functions were compared with those of cisplatin and carboplatin, using a renal cortical slice system.Methods and results Rat renal cortical slices were incubated with 0.25mM to 2.0mM of oxaliplatin, cisplatin, on carboplatin at 37°C for 120min. Para-amino hippuric acid (PAH) accumulation, gluconeogenesis, and ATP content in the rat renal slices were determined. PAH accumulation was not inhibited by carboplatin, but it was signific-antly inhibited by oxaliplatin and cisplatin. Inhibition of PAH accumulation by cisplatin was greater than that by oxaliplatin. Gluconeogenesis was not decreased by carboplatin, but it was suppressed by oxaliplatin and cisplatin in a dose-dependent manner. The decrease in gluconeogenesis induced by oxaliplatin was significantly greater than that induced by cisplatin. ATP content in the renal slices was decreased by oxaliplatin, cisplatin, and carboplatin to almost the same extent. As an in vivo experiment, 21.6mmole/kg of oxaliplatin, cisplatin, or carboplatin was injected into rats; then blood urea nitrogen (BUN) and serum creatinine were determined on day 4. Significantly elevated levels of BUN and serum creatinine were observed only in the rats injected with cisplatin.Conclusions Oxaliplatin did not cause nephrotoxicity in the in vivo study; however, the nephrotoxic pattern of oxaliplatin observed in the renal cortical-slice system resembled that of cisplatin. The reason why oxaliplatin is less nephrotoxic than cisplatin in vivo could not be fully elucidated in the present experiment using the renal cortical-slice system.     

Advanced Glycation End Products (AGEs), but not High Glucose, Inhibit the Osteoblastic Differentiation of Mouse Stromal ST2 Cells Through the Suppression of Osterix Expression, and Inhibit Cell Growth and Increasing Cell Apoptosis

Diabetes mellitus is known to be associated with osteoporotic fractures through a decrease in osteoblastic bone formation rather than an increase in osteoclastic bone resorption. However, its precise mechanism is unknown, and we examined whether or not high glucose or advanced glycation end products (AGEs), which play key roles in the pathogenesis and complications of diabetes, would affect the osteoblastic differentiation, growth, and apoptosis of mouse stromal ST2 cells. Ten to 200?μg/mL AGE2 or AGE3 alone dose-dependently inhibited the mineralization. AGE2 or AGE3 alone (200?μg/mL) significantly inhibited alkaline phosphatase (ALP) activities as well as the mineralization of the cells (p?相似文献   

Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: importance of decreased renal parathyroid hormone sensitivity

BACKGROUND: We hypothesized that impaired peripheral sensitivity to parathyroid hormone (PTH) may play a role in reelevation of PTH after successful operation for primary hyperparathyroidism (pHPT). METHODS: Factors affecting reelevation of PTH were determined in 90 patients who underwent parathyroidectomy for pHPT. PTH/nephrogenous cyclic adenosine monophosphate ratio, as an index of renal resistance to PTH, was examined in relation to factors shown to influence reelevation of PTH. RESULTS: Serum PTH levels were elevated above the upper limit of normal in 23 patients (26%) at 1 week and in 39 patients (43%) at 1 month after parathyroidectomy. These 39 normocalcemic patients with elevated serum PTH at 1 month after parathyroidectomy had a higher preoperative serum level of PTH and lower serum phosphate and 25-hydroxyvitamin D (25OHD) concentrations than those with normal PTH (n = 59). Elevated PTH and low 25OHD were shown by multivariate analysis to be significant predictors of reelevation of PTH. Renal resistance to PTH was higher in patients with vitamin D deficiency or renal insufficiency than in patients with normal serum vitamin D concentrations or normal renal function, and it increased according to increases in levels of PTH. CONCLUSIONS: The mechanism of PTH reelevation in patients with pHPT after successful parathyroidectomy appears to be renal resistance to PTH.     

Identification of physical and psychosocial problems associated with diabetic nephropathy using the International Classification of Functioning,Disability and Health Core Set for Diabetes Mellitus

Background

We previously demonstrated validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus (ICF-CS for DM) in patients with diabetic nephropathy (DMN). The objective of the present study was to identify differences in experience of physical and psychosocial problems between DMN patients with and without hemodialysis (HD), and diabetes patients without nephropathy using the ICF-CS for DM.

Methods

A total of 302 diabetes outpatients (men, 68 %; mean age, 62 years) were interviewed using four components of the ICF-CS for DM including “Body functions”, “Body structures”, “Activities and participation”, and “Environmental factors”.

Results

The mean number of categories in which difficulty was experienced in the four components was significantly greater in DMN patients with HD followed by DMN patients without HD, and diabetes patients without nephropathy (23.9 vs. 18.0 vs. 13.1, respectively). Multivariate logistic regression models revealed that, compared with diabetes patients without nephropathy, diabetes patients with nephropathy were more likely to have difficulty with physical problems and social activities and participation. Among DMN patients, dialysis patients were found to have larger numbers of problems, and face difficulty with employment status after adjusting for sex, age, type, and duration of diabetes.

Conclusion

The results of this study using the ICF-CS for DM identified the areas for improvement among physical and psychosocial problems in DMN patients with and without HD in contrast to diabetes patients without nephropathy.