A case of reformed coronoid process and mandibular angle after coronoidectomy and anglectomy for masticatory muscle tendon-aponeurosis hyperplasia

Masticatory muscle tendon-aponeurosis hyperplasia is a newly defined disease entity in Japan, in which limited mouth opening results from limited masticatory muscle extension caused by hyperplasia of the tendon and aponeurosis. Recently, we encountered a rare case of reformed bilateral coronoid process and mandibular angle after coronoidectomy and anglectomy. A 19-year-old female with gradually progressive trismus had been diagnosed with this disease. Under general anesthesia, she received coronoidotomy of the bilateral coronoid process and anglectomy. At 1 week postoperatively, trismus was improved. At 6 months postoperatively, panoramic imaging showed the initiation of bilateral reformed coronoid process and mandibular angle. At 3 years postoperatively, computed tomography (CT) and three-dimensional reconstructed CT (3D-CT) demonstrated reformed coronoid process and mandibular angle. However, the maximum mouth opening length was not decreased. She continued to perform mandibular condyle movement exercise every day. Panoramic imaging is a very useful examination for evaluating bone reformation after coronoidectomy and anglectomy for masticatory muscle tendon-aponeurosis hyperplasia. In particular, CT and 3D-CT demonstrated reformed coronoid process and mandibular angle. Postoperative mouth-opening training is an important prognostic factor to prevent the recurrence of trismus in this disease.     

Clinical and Immunological Characterization of ICF Syndrome in Japan

Objective

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare autosomal recessive primary immunodeficiency. Hypogammaglobulinemia is a major manifestation of ICF syndrome, but immunoglobulin replacement therapy does not seem to be effective for some ICF patients. Therefore, we aimed to reassess the immunological characteristics of this syndrome.

Methods

Eleven Japanese patients with ICF syndrome were enrolled. We performed whole-exome sequencing in four cases and homozygosity mapping using SNP analysis in two. We evaluated their clinical manifestations and immunological status.

Results

We newly diagnosed six ICF patients who had tentatively been diagnosed with common variable immunodeficiency. We identified two novel mutations in the DNMT3B gene and one novel mutation in the ZBTB24 gene. All patients showed low serum IgG and/or IgG₂ levels and were treated by periodic immunoglobulin replacement therapy. Three of the six patients showed worse results of the mitogen-induced lymphocyte proliferation test. Analyses of lymphocyte subpopulations revealed that CD19⁺CD27⁺ memory B cells were low in seven of nine patients, CD3⁺ T cells were low in three patients, CD4/8 ratio was inverted in five patients, CD31⁺ recent thymic emigrant cells were low in two patients, and CD19⁺ B cells were low in four patients compared with those in the normal controls. ICF2 patients showed lower proportions of CD19⁺ B cells and CD16⁺56⁺ NK cells and significantly higher proportions of CD3⁺ T cells than ICF1 patients. T cell receptor excision circles were undetectable in two patients. Despite being treated by immunoglobulin replacement therapy, three patients died of influenza virus, fatal viral infection with persistent Epstein–Barr virus infection, or JC virus infection. One of three dead patients showed normal intelligence with mild facial anomaly. Two patients presented with autoimmune or inflammatory manifestations. Infectious episodes decreased in three patients who were started on trimethoprim–sulfamethoxazole and/or antifungal drugs in addition to immunoglobulin replacement therapy. These patients might have suffered from T cell immunodeficiency.

Conclusion

These results indicate that patients with ICF syndrome have a phenotype of combined immunodeficiency. Thus, to achieve a better prognosis, these patients should be treated as having combined immunodeficiency in addition to receiving immunoglobulin replacement therapy.

     

K14‐EGFP‐miR‐31 transgenic mice have high susceptibility to chemical‐induced squamous cell tumorigenesis that is associating with Ku80 repression

Squamous cell carcinoma (SCC) occurring in the head and neck region and the esophagus causes tremendous cancer mortality around the world. miR‐31 is among the most eminently upregulated MicroRNAs in SCC, when it occurs in the head and neck region and the esophagus. We established miR‐31 transgenic mouse lines, in which miR‐31 is under the control of the K14 promoter. 4‐nitroquinoline 1‐oxide (4NQO) is a mutagen that causes double strand breaks. The transgenic mice exhibited a higher potential for tumor induction than wild‐type (Wt) mice of the tongue and esophagus after 4NQO treatment. After 4NQO treatment or irradiation, p‐γH2AX expression in squamous epithelium of transgenic mice was increased more than in Wt mice. Exogenous expression of miR‐31 was also found to be associated with the higher p‐γH2AX expression induced by 4NQO in human oral SCC (OSCC) cell lines. The repair genes PARP1 and Ku80 were validated as new targets of miR‐31 in human OSCC cell lines, and were found to be downregulated in the squamous epithelium of the tongue in transgenic mice. However, only the downregulation of Ku80 was essential for maintaining the high level of p‐γH2AX induced by 4NQO in OSCC cells. Inverse expression profiles for miR‐31 and Ku80 were noted in human OSCC tissue. Our study identifies the high sensitivity of K14‐EGFP‐miR‐31 transgenic mice to chemical carcinogen‐induced squamous cell tumorigenesis and shows that this seems to be associated with the downregulation of Ku80 and an impairment of repair activity in squamous cells, which are mediated by miR‐31.     

Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cyclin‐dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6–cyclin D1 complex controls the cell cycle transition from G₁ phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression.     

Using discrete-event simulation in strategic capacity planning for an outpatient physical therapy service

This study uses a simulation model as a tool for strategic capacity planning for an outpatient physical therapy clinic in Taipei, Taiwan. The clinic provides a wide range of physical treatments, with 6 full-time therapists in each session. We constructed a discrete-event simulation model to study the dynamics of patient mixes with realistic treatment plans, and to estimate the practical capacity of the physical therapy room. The changes in time-related and space-related performance measurements were used to evaluate the impact of various strategies on the capacity of the clinic. The simulation results confirmed that the clinic is extremely patient-oriented, with a bottleneck occurring at the traction units for Intermittent Pelvic Traction (IPT), with usage at 58.9 %. Sensitivity analysis showed that attending to more patients would significantly increase the number of patients staying for overtime sessions. We found that pooling the therapists produced beneficial results. The average waiting time per patient could be reduced by 45 % when we pooled 2 therapists. We found that treating up to 12 new patients per session had no significantly negative impact on returning patients. Moreover, we found that the average waiting time for new patients decreased if they were given priority over returning patients when called by the therapists.     

Lifestyle intervention might easily improve blood pressure in hypertensive men with the C genotype of angiotensin II type 2 receptor gene

BACKGROUND/OBJECTIVESRecent studies have reported an association of the angiotensin II type 2 receptor (AT2R) 3123Cytosine/Adenine (3123C/A) polymorphism with essential hypertension and cardiovascular diseases. The purpose of the study was to investigate whether the AT2R 3123C/A polymorphism affects blood pressure for free-living hypertensive men during a 5-month intervention period.SUBJECTS/METHODSThe subjects were free-living hypertensive Japanese men aged 40 to 75 years who agreed to intervention in the period from 2004 to 2011. Detection of the AT2R 3123C/A polymorphism was determined by polymerase chain reaction. The dietary intervention was designed to decrease salt level and to increase potassium level through cooking instructions and self-monitoring of the diet. The exercise session consisted of activities such as stretching, resistance training, and walking. Blood pressure, urinary sodium and potassium excretion, dietary and lifestyle data, and non-fasting venous blood sample were collected at baseline and after the intervention period.RESULTSThirty nine subjects were eligible for participation and the follow-up rate was 97.4%. The C allele proportion was 57.9%. AT2R 3123C/A polymorphism was X-chromosome-linked, therefore we analyzed the C and A genotypes. At baseline, no significant differences were observed between the genotype groups. After the intervention, there were no significant differences in lifestyle habit between the groups. Nevertheless, the estimated salt excretion (g/day) was significantly decreased only in the C genotype (13.0-10.3, P = 0.031). No significant change was observed in systolic blood pressure (SBP) (mmHg) in the A genotype, but a significant decrease was observed in the C genotype (150.0-141.5, P = 0.024).CONCLUSTIONSIn the C genotype, it might be easy to improve SBP through lifestyle intervention in free-living hypertensive Japanese men, however generalization could not be achieved by the small sample size.     

Effect of Switching Therapy to Pegaptanib in Eyes With the Persistent Cases of Exudative Age-Related Macular Degeneration

Purpose of this study was to evaluate the efficacy of switching to pegaptanib monotherapy for persistent cases of exudative age-related macular degeneration (AMD).Out of 296 eyes of 296 patients treated with ranibizumab or ranibizumab combined with photodynamic therapy (PDT), 50 eyes of 50 AMD patients were found to be resistant to these treatments. Over a 12-month period, intravitreal pegaptanib (IVP) 0.3 mg was administered at intervals of 6 weeks until the exudation disappeared prospectively. All patients were examined with the following tests: best-corrected visual acuity (BCVA) and central retinal thickness (CRT), determined at the initial visit, before the first IVP (baseline), and at 12 months. The factors responsible for achieving dry macula with IVP were examined statistically.The rate of persistent cases with intravitreal ranibizumab (IVR) and/or PDT was 17.0%. The mean number of IVPs administered was 5.4 (range, 2–9). Logarithm of the minimal angle of resolution BCVA at 12 months was stable or improved by ≥0.3 in 49 eyes (98.0%), with a significant improvement noted between the baseline and final BCVA (P = 0.01, paired t test). The CRT (mean ± standard deviation) was 446.9 ± 150.6 µm at the initial visit, 414.5 ± 146.5 µm at baseline, and 318.7 ± 99.0 µm at 12 months. There was a significant decrease in the mean CRT between the measurements at baseline and at 12 months after the first IVP (P = 0.002, Bonferroni correction). At 12 months, the exudative change was completely resolved in 27 eyes (54.0%) and reduced in 21 eyes (42.0%). The number of previous IVR treatments was significantly correlated with dry macula at 12 months.After switching therapy to pegaptanib in persistent cases of AMD, most patients maintained or improved their BCVA and exhibited a positive treatment response at 12 months.