Poor responses to tyrosine kinase inhibitors in a child with precursor B‐cell acute lymphoblastic leukemia with SNX2‐ABL1 chimeric transcript

In addition to BCR, various rare fusion partners for the ABL1 gene have been reported in leukemia. We have identified the fusion gene SNX2‐ABL1 in a pediatric case of acute lymphoblastic leukemia (ALL), which has only once previously been reported in an adult patient. Cytogenetic analysis detected this fusion gene arising from a t(5;9)(q22;q34) translocation. ALL cells carrying a SNX2‐ABL1 fusion exhibited a BCR‐ABL1+ ALL‐like gene expression profile. The patient poorly responded to dasatinib but partially responded to imatinib. Treatment using tyrosine kinase inhibitors requires further investigation to optimize the genotype‐based treatment stratification for patients with SNX2‐ABL1 fusion.     

Clinical anatomy of the subserous layer: An amalgamation of gross and clinical anatomy

The 1998 edition of Terminologia Anatomica introduced some currently used clinical anatomical terms for the pelvic connective tissue or subserous layer. These innovations persuaded the present author to consider a format in which the clinical anatomical terms could be reconciled with those of gross anatomy and incorporated into a single anatomical glossary without contradiction or ambiguity. Specific studies on the subserous layer were undertaken on 79 Japanese women who had undergone surgery for uterine cervical cancer, and on 26 female cadavers that were dissected, 17 being formalin‐fixed and 9 fresh. The results were as follows: (a) the subserous layer could be segmentalized by surgical dissection in the perpendicular, horizontal and sagittal planes; (b) the segmentalized subserous layer corresponded to 12 cubes, or ligaments, of minimal dimension that enabled the pelvic organs to be extirpated; (c) each ligament had a three‐dimensional (3D) structure comprising craniocaudal, mediolateral, and dorsoventral directions vis‐á‐vis the pelvic axis; (d) these 3D‐structured ligaments were encoded morphologically in order of decreasing length; and (e) using these codes, all the surgical procedures for 19th century to present‐day radical hysterectomy could be expressed symbolically. The establishment of clinical anatomical terms, represented symbolically through coding as demonstrated in this article, could provide common ground for amalgamating clinical anatomy with gross anatomy. Consequently, terms in clinical anatomy and gross anatomy could be reconciled and compiled into a single anatomical glossary. Clin. Anat. 29:508–515, 2016. © 2015 Wiley Periodicals, Inc.     

Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster‐associated pain including post‐herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2–3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3–4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.     

Mutations in the fifth immunoglobulin-like domain of kit are common and potentially sensitive to imatinib mesylate in feline mast cell tumours

The purpose of the current study was to investigate the mutation status of KIT in feline mast cell tumours (MCTs) and to examine the effects of tyrosine kinase inhibition on the phosphorylation of mutant kit in vitro and in clinical cases of cats. Sequence analysis of KIT identified mutations in 42/62 MCTs (67·7%). The vast majority of the mutations were distributed in exons 8 and 9, both of which encode the fifth immunoglobulin-like domain (IgD) of kit. All five types of kit with a mutation in the fifth IgD were then expressed in 293 cells and examined for phosphorylation status. The mutant kit proteins showed ligand-independent phosphorylation. The tyrosine kinase inhibitor imatinib mesylate suppressed the phosphorylation of these mutant kit proteins in transfectant cells. In a clinical study of 10 cats with MCTs, beneficial response to imatinib mesylate was observed in 7/8 cats that had a mutation in the fifth IgD of kit in tumour cells. Mutations in the fifth IgD of kit thus appear to be common and potentially sensitive to imatinib mesylate in feline MCTs. These data provide an in vivo model for paediatric mastocytosis where mutations in the fifth IgD of kit also occur.     

Enamel remineralization effect of a dentifrice containing calcium sodium phosphosilicate: an optical coherence tomography observation

Objective: The purpose of this study was to examine the effects of a dentifrice containing 5% calcium sodium phosphosilicate (CSP) on the remineralization of the enamel using optical coherence tomography (OCT).

Materials and methods: Bovine incisors were sliced and shaped in a rectangular form. One group of five specimens was treated with undersaturated 0.1 M lactic acid buffer solution (pH 4.75) for 10?min and then placed in artificial saliva (pH 7.0) (De group). Other specimens were stored in solutions of toothpaste containing CSP for 10?min, followed by 10-min immersion in the lactic acid buffer solution twice a day before storage in artificial saliva (CSP group). An additional group was stored in only artificial saliva (control group). OCT imaging on the selected location of the enamel surface was performed. The peak intensity and width at 1/e² were recorded in each of the six areas on the sample and averaged, and the sample size of each group was six. The integrated value in units (dB?×?μm) was calculated in the area of peak intensity. The data for each group was subjected to one-way repeated-measures ANOVA and Tukey HSD tests (α?=?0.05).

Results: The changes in integrated values of each group were different. A slight but significant increase in the integrated value was observed in the control group, whereas a slight but significant decrease in the value was observed the De group. Integrated values increased in the CSP group.

Conclusions: Remineralization occurred upon immersion in the toothpaste containing CSP.     

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.     

Google Home: smart speaker as environmental control unit

Environmental Control Units (ECU) are devices or a system that allows a person to control appliances in their home or work environment. Such system can be utilized by clients with physical and/or functional disability to enhance their ability to control their environment, to promote independence and improve their quality of life. Over the last several years, there have been an emergence of several inexpensive, commercially-available, voice activated smart speakers into the market such as Google Home and Amazon Echo. These smart speakers are equipped with far field microphone that supports voice recognition, and allows for complete hand-free operation for various purposes, including for playing music, for information retrieval, and most importantly, for environmental control. Clients with disability could utilize these features to turn the unit into a simple ECU that is completely voice activated and wirelessly connected to appliances. Smart speakers, with their ease of setup, low cost and versatility, may be a more affordable and accessible alternative to the traditional ECU.

• Implications for Rehabilitation

• Environmental Control Units (ECU) enable independence for physically and functionally disabled clients, and reduce burden and frequency of demands on carers.

• Traditional ECU can be costly and may require clients to learn specialized skills to use.

• Smart speakers have the potential to be used as a new-age ECU by overcoming these barriers, and can be used by a wider range of clients.

     

The exploration of population pharmacokinetic model for meropenem in augmented renal clearance and investigation of optimum setting of dose

In recent years, augmented renal clearance (ARC), in which renal function is excessively enhanced, has been reported, and its influence on β-lactam antibiotics has been investigated. In this study, we aimed to determine the optimum population pharmacokinetic model of meropenem in patients with sepsis with ARC, and evaluated dosing regimens based on renal function. Seventeen subjects (6 with ARC and 11 without) were enrolled in this study. Predicted meropenem concentrations were evaluated for bias and precision using the Bland–Altman method. To examine the dosing regimen, Monte Carlo simulation was performed to calculate the cumulative fraction of response (CFR). In patients with ARC, the bias (average of the predicted value and measured value residuals) of models constructed by Crandon et al. (2011), Roberts et al. (2009), and Jaruratanasirikul et al. (2015) were 5.96 μg/mL, 10.91 μg/mL, and 4.41 μg/mL, respectively. Following 2 g meropenem every 8 h (180 min infusion), CFR ≥ 90%, a criterion of success for empirical therapy, was achieved, even with creatinine clearance of 130–250 mL/min. For patients with sepsis and ARC, the model of Jaruratanasirikul et al. showed the highest degree of accuracy and precision and confirmed the efficacy of the meropenem dosing regimen in this patient population.     

Influences of environmental noise level and respiration rate on the accuracy of acoustic respiration rate monitoring

We tested the hypothesis that the environmental noise generated by a forced-air warming system reduces the monitoring accuracy of acoustic respiration rate (RRa). Noise levels were adjusted to 45–55, 56–65, 66–75, and 76–85 dB. Healthy participants breathed at set respiration rates (RRset) of 6, 12, and 30/min. Under each noise level at each RRset, the respiration rates by manual counting (RRm) and RRa were recorded. Any appearance of the alarm display on the RRa monitor was also recorded. Each RRm of all participants agreed with each RRset at each noise level. At 45–55 dB noise, the RRa of 13, 17, and 17 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of 14, 17, and 16 participants at 56–65 dB noise, agreed with RRset of 6, 12, and 30/min, respectively. At 66–75 dB noise, the RRa of 9, 15, and 16 participants agreed with RRset of 6, 12, and 30/min, respectively. The RRa of one, nine, and nine participants at 76–85 dB noise agreed with RRset of 6, 12, and 30/min, respectively, which was significantly less than the other noise levels (P?<?0.05). Overall, 72.9% of alarm displays highlighted incorrect values of RRa. In a noisy situation involving the operation of a forced-air warming system, the acoustic respiration monitoring should be used carefully especially in patients with a low respiration rate.