Atypical teratoid rhabdoid tumor in the cavernous sinus of a toddler presenting with oculomotor nerve palsy

Introduction

Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant, and aggressive tumor of infancy. Although the prognosis of ATRT has been extremely poor, recently, the first prospective study for ATRT demonstrated improvement of prognosis. On the other hands, oculomotor nerve palsy is rare in children and the most frequent etiology is congenital. To our knowledge, only a few ATRT cases presenting with oculomotor nerve palsy have been reported, but ATRT originating from the cavernous sinus (CS) has not yet been reported.

Case report

An 18-month-old girl with right oculomotor nerve palsy was admitted, and a small mass in the right CS was detected with brain MRI. Although she received steroid pulse therapy and antimicrobial therapy, the mass continued to enlarge. One month after admission, the mass was partially resected and diagnosed as ATRT. Multimodal therapy including anthracycline-based chemotherapy, intrathecal therapy, and cranial irradiation was performed. Twenty-nine months after resection, she was alive without tumor relapse, but the oculomotor nerve palsy persisted.

Conclusion

This is the first reported case of ATRT located in the CS presenting with oculomotor nerve palsy. This case was successfully treated with partial removal of the tumor, a new chemotherapy regimen for ATRT and cranial X-ray irradiation.     

Urethra actively opens from the very beginning of micturition: A new concept of urethral function

Transvaginal or transrectal ultrasound was carried out in an adult female and a male volunteer during micturition. Although the male urethra was enclosed by the prostate, its construction and the function were almost identical to the female urethra. The anterior fibromuscular stroma was not a part of the prostate, but was a part of the urethral muscle. The urethra was surrounded by a thick single muscle unit, developed only on the anterior and lateral sides of the urethra. When the participant wished to urinate, the initial motion was not a bladder contraction, but an active opening of the urethral lumen by the muscle unit. The same unit closed the urethra when continence was kept. In conclusion, the main function of the urethra is thought to be not a closure, but an opening to control the entire micturition process, rather than the bladder being primarily responsible for the control of micturition.     

Delayed renal dysfunction after total body irradiation in pediatric malignancies

The purpose of this study was to retrospectively evaluate the incidence of delayed renal dysfunction after total body irradiation (TBI) in long-term survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and 2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for HSCT at Chiba University Hospital. Nine patients who survived for more than 5 years were enrolled in this study. No patient had any evidence of renal dysfunction prior to the transplant according to their baseline creatinine levels. The median age at the time of diagnosis was 6 years old (range: 1–17 years old). The follow-up period ranged from 79–170 months (median: 140 months). Renal dysfunction was assessed using the estimated glomerular filtration rate (eGFR). The TBI dose ranged from 8–12 Gy delivered in 3–6 fractions over 2–3 d. The patients were treated with linear accelerators in the supine position, and the radiation was delivered to isocentric right–left and left–right fields via the extended distance technique. The kidneys and the liver were not shielded except in one patient with a left adrenal neuroblastoma. No patient required hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The remaining patients did not demonstrate any eGFR deterioration. Only one patient developed hypertension. By evaluating the changes in eGFR, renal dysfunction among long-term survivors of TBI/HSCT could be detected. Our results suggested that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects renal function.     

Sociogeographic Variation in the Effects of Heat and Cold on Daily Mortality in Japan

Background

Ambient temperature affects mortality in susceptible populations, but regional differences in this association remain unclear in Japan. We conducted a time-series study to examine the variation in the effects of ambient temperature on daily mortality across Japan.

Methods

A total of 731 558 all-age non-accidental deaths in 6 cities during 2002–2007 were analyzed. The association between daily mortality and ambient temperature was examined using distributed lag nonlinear models with Poisson distribution. City-specific estimates were combined using random-effects meta-analysis. Bivariate random-effects meta-regressions were used to examine the moderating effect of city characteristics.

Results

The effect of heat generally persisted for 1 to 2 days. In warmer communities, the effect of cold weather lasted for approximately 1 week. The combined increases in mortality risk due to heat (99th vs 90th percentile of city-specific temperature) and cold (first vs 10th percentile) were 2.21% (95% CI, 1.38%–3.04%) and 3.47% (1.75%–5.21%), respectively. City-specific effects based on absolute temperature changes were more heterogeneous than estimates based on relative changes, which suggests some degree of acclimatization. Northern populations with a cool climate appeared acclimatized to low temperature but were still vulnerable to extreme cold weather. Population density, average income, cost of property rental, and number of nurses appeared to influence variation in heat effect across cities.

Conclusions

We noted clear regional variation in temperature-related increases in mortality risk, which should be considered when planning preventive measures.Key words: heat, cold, mortality, time-series, distributed lag     

Cellular and molecular mechanisms underlying NOD2 risk-associated polymorphisms in Crohn's disease

The discovery that polymorphisms in the NOD2 (nucleotide-binding oligomerization domain containing 2) gene are associated with a greatly increased risk for the development of Crohn's disease has provided a means to achieve a deeper understanding of the dysregulation of mucosal immune responses to the commensal intestinal organisms that is thought to underlie this disease. NOD2 is a NOD-like receptor (NLR) family member that senses and responds to bacterial wall peptides; thus, the most widely held view of the relation of the NOD2 polymorphisms with Crohn's disease is that these polymorphisms lead to deficient immune responses to gut bacteria, and these, in turn, lead to quantitative or qualitative changes in the bacterial population in the gut lumen or lamina propria that cause inflammation at this site. Initially, this view was based mainly on the observation that defective NOD2 function can result in reduced α-defensin production by intestinal Paneth cells and that such impairment leads to loss of host defense against gut bacteria. In this review, we reconsider this possibility and marshal evidence that it is not in fact likely to be a prime element of Crohn's disease causation. More recently, evidence has been accumulating that the NOD2 dysfunction leads to Crohn's inflammation by inducing changes in the gut microbiome that influence immune effector or regulatory function. We review the strengths and weaknesses of this emerging hypothesis. Finally, we consider the possibility that NOD2 dysfunction can lead to inflammation because of a second and somewhat overlooked aspect of its function, that as an immunoregulator of innate immune responses. In particular, we review the body of evidence that NOD2 stimulation activates a cross-tolerance response that downregulates and thus prevents excessive TLR responses that cause Crohn's inflammation.     

ClpB chaperone passively threads soluble denatured proteins through its central pore

ClpB disaggregase forms a ring‐shaped hexamer that threads substrate proteins through the central pore using energy from ATP. The ClpB protomer consists of an N‐terminal domain, a middle domain, and two AAA+ modules. These two AAA+ modules bind and hydrolyze ATP and construct the core of the hexameric ring. Here, we investigated the roles of the two AAA+ modules in substrate threading. BAP is an engineered ClpB that can bind ClpP proteolytic chamber; substrates threaded by BAP are degraded by ClpP. We combined BAP with conserved motif mutations in two AAA+ modules and measured the steady‐state rates of threading of soluble denatured proteins by these mutants over a range of substrate concentrations. By fitting the data to the Michaelis‐Menten equation, k_cat and K_m values were determined. We found that the kinetic parameters of the substrate threading correlate with the type of mutation introduced rather than the ATPase activity of the mutant. Moreover, some mutants having no or marginal ATPase activity could thread denatured proteins significantly. These results indicate that ClpB can passively thread soluble denatured proteins.     

Paracorporeal ventricular assist device as a bridge to transplant candidacy in the era of implantable continuous-flow ventricular assist device

Ventricular assist devices (VADs) have long been used as bridge to transplant therapy (BTT). Nipro-Toyobo paracorporeal pulsatile-flow VAD (nt-VAD) was the only device available until April 2011, when implantable continuous-flow VADs (cf-VADs) became available. Although cf-VADs are central to BTT, nt-VAD remains a necessary option. We aimed to clarify the role of nt-VAD in an era of increasing cf-VAD use. We retrospectively reviewed patients who underwent VAD implantation at the National Cerebral and Cardiovascular Center from May 2011 to March 2013. Characteristics were compared between the nt-VAD and cf-VAD groups. Twenty-nine patients (mean age 37.7 ± 11.1 years, 23 males) underwent VAD implantation. Fifteen patients initially received nt-VADs, although 4 were converted to cf-VADs. Of these 15 patients, 3 were too small for cf-VADs and 2 needed bilateral ventricular support. The remaining 10 patients received nt-VADs (7 patients at INTERMACS level 1 and 3 at level 2). The nt-VAD group patients had significantly more preoperative mechanical circulatory support and were in a more critical condition before VAD implantation than the cf-VAD group. The 2-year survival rate was not significantly different. Despite the critical conditions of nt-VAD patients, their overall survival is not statistically inferior to that of cf-VAD patients. nt-VAD is a good option as a BTC for the patient with urgent and critical condition.     

Metabolic and cardiovascular responses during voluntary pedaling exercise with electrical muscle stimulation

Purpose

We aimed to test the effect of additional electrical muscle stimulation (EMS) during moderate-intensity voluntary pedaling exercise on metabolic and cardiovascular responses.

Methods

Eleven healthy male subjects performed moderate-intensity pedaling exercise at a constant workload (80 % of ventilatory threshold) for 20 min while EMS was applied to thigh muscles from 5 to 10 min and from 15 to 20 min during the exercise.

Results

A significantly higher oxygen uptake (VO₂), heart rate, and respiratory gas exchange ratio were observed during the exercise periods with EMS despite the constant workload. These changes were accompanied by an elevated blood lactate concentration, suggesting the existence of additional fast-twitch motor unit (MU) recruitment during the exercise with EMS.

Conclusion

Our data suggest that the use of intermittent EMS during a constant load exercise mimics the high-intensity interval training, possibly due to additional fast-twitch MU recruitment and co-contractions of the quadriceps and hamstrings muscles, leading to higher anaerobic metabolism and a lower mechanical efficiency.