Biomineralization is the process by which hydroxyapatite is deposited in the extracellular matrix. Physiological mineralization occurs in hard tissues, whereas pathological calcification occurs in soft tissues. The first step of mineralization is the formation of hydroxyapatite crystals within matrix vesicles that bud from the surface membrane of hypertrophic chondrocytes, osteoblasts, and odontoblasts. This is followed by propagation of hydroxyapatite into the extracellular matrix and its deposition between collagen fibrils. Extracellular inorganic pyrophosphate, provided by NPP1 and ANKH, inhibits hydroxyapatite formation. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes pyrophosphate and provides inorganic phosphate to promote mineralization. Inorganic pyrophosphate, pyridoxal phosphate, and phosphoethanolamine are thought to be the physiologic substrates of TNAP. These accumulate in the event of TNAP deficiency, e.g., in cases of hypophosphatasia. The gene encoding TNAP is mapped to chromosome 1, consists of 12 exons, and possesses regulatory motifs in the 5'-untranslated region. Inhibition of TNAP enzymatic activity suppresses TNAP mRNA expression and mineralization in vitro. Hypophosphatasia is an inherited systemic bone disease characterized by hypomineralization of hard tissues. The phenotype of hypophosphatasia is varied. To date, more than 200 mutations in the TNAP gene have been reported. Knockout mice mimic the phenotypes of severe hypophosphatasia. Among the mutations in the TNAP gene, c.1559delT is frequent in the Japanese population. This frameshift mutation results in the expression of an abnormally long protein that is degraded in cells. DNA-based prenatal diagnosis using chorionic villus sampling has been developed, but requires thorough genetic counseling. Although hypophosphatasia is untreatable at present, the recent success of enzyme replacement therapy offers promise. The problems presented by impaired mineralization in age-related chronic diseases, such as pathologic calcification and decreasing physiological mineralization are growing in importance. Strategies for preventing pathologic calcification using TNAP and NPP1 are in development. A nutrigenomic approach, based on the relationship between TNAP gene polymorphism and bone mineral density, is also discussed.

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Background: Several reports have validated the criteria for damage control surgery (DCS). However, although metabolic acidosis and body temperature can be measured quickly, tests for predicting the severity of coagulopathy require special laboratory equipment and take 15 to 30 minutes. Such delays could be life-threatening for patients requiring DCS. The aim of this study was to establish simplified and practical criteria to enable rapid decision-making regarding the need for DCS.
Methods: Thirty-four consecutive patients with unstable hemodynamics after initial fluid resuscitation who had undergone DCS for severe abdominal or pelvic injuries were retrospectively analyzed. The patients' characteristics, clinical courses, laboratory data, and outcomes were reviewed using the data contained in their medical records.
Results: The overall survival rate was 55.9% (survivors group: n=19; nonsurvivors group: n=15), which was similar to the calculated mean probability of survival (Ps=0.5671). At the start of surgery, the systolic blood pressure (SBP) was less than 90 mm Hg in all cases in which surgery failed, and the mean SBP in the nonsurvivors group (69.6 ± 14.8 mm Hg) was significantly lower than that in the survivors group (93.2 ± 22.9 mm Hg, p=0.006). Except in two cases, the value of the base excess in the nonsurvivors group was less than -7.5 mmol/L, and the mean base excess (-11.5 ± 5.3 mmol/L) in the nonsurvivors group was significantly less than that in the survivors group (-5.5 ± 4.9 mmol/L, p=0.008) at the start of surgery. The core temperature at the start of surgery was less than 35.5°C in all cases in the nonsurvivors group. On the basis of these results, three indicators (SBP less than 90 mm Hg, base excess less than -7.5 mmol/L, and core temperature less than 35.5°C at the start of surgery) were identified. The success rate of DCS in patients who possessed all three indicators (28.6% ) was significantly lower than that in patients who did not possess all three indicators (75.0%; p=0.014).
Conclusion: Our results indicate that surgeons should decide to perform DCS when only one or two criteria defined in this study are met and should not wait for all three criteria. Although our proposed criteria are not strict and may broaden the indications for DCS, leading to an increase in the number of DCS procedures, saving the lives of patients who have sustained severe torso trauma must be the priority; 'over-triage' may be acceptable in situations where an appropriate decision-making protocol has been followed.

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Objectives: Chronic rhinosinusitis associated with asthma is often difficult to treat effectively with intranasal corticosteroids alone. Thus, the aim of this study was to evaluate the effectiveness of combination treatment with an intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in reducing the size of nasal polyps.
Methods: The subjects of this study were 20 patients with chronic rhinosinusitis associated with adult-onset asthma, which was being treated with inhaled corticosteroids. All patients were treated with intranasal fluticasone propionate, 200 μg/day, and montelukast, 10 mg/day, for 1 year. The size of nasal polyps and the score of sinus shadows were assessed with nasal endoscopy and computed tomography (CT), respectively, before and after treatment. The peripheral blood eosinophil counts were also evaluated before and after treatment.
Results: Nasal polyps were significantly smaller after both 6 months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The decrease in the shadow score was statistically significant after both 6 months (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in peripheral blood eosinophil counts were also seen after both 6 months (p<0.05) and 12 months of treatment (p<0.01). A significant correlation was found between the rate of change in the peripheral blood eosinophil count and that in the CT score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007).
Conclusion: Combined treatment with intranasal fluticasone propionate and montelukast, for at least 1 year, is effective for chronic rhinosinusitis associated with adult-onset asthma.

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We present a case of acute pancreatitis in a 14-year-old girl which fulfilled the diagnostic criteria of autoimmune pancreatitis (AIP) and responded to corticosteroid therapy. Imaging studies revealed that the main pancreatic duct was narrow in the head of the pancreas but had been dilated in the body at an earlier stage. The pancreatitis recurred twice when the prednisolone dose was reduced to 10 mg or less but responded each time to an increased dose and has been kept under control with low-dose prednisolone therapy for 3 years since onset. Repeated magnetic resonance cholangiopancreatography during steroid therapy revealed an improvement of the narrowing of the main pancreatic duct in the head and dilation of the duct in the body. AIP in younger patients has distinct clinical features, such as presentation with epigastralgia, back pain without jaundice, and elevated serum amylase levels. The serum level of IgG4 is rarely increased in young patients, indicating a different disease mechanism than for cases in elderly patients. Given the excellent response of this condition to steroid therapy, AIP should be considered even in young children and adolescents when the diagnosis of idiopathic pancreatitis is suggested.

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We report 2 cases of clitoromegaly, 1 in a patient with true hermaphroditism, and the other in a patient with adrenogenital syndrome. Both were treated surgically with reduction clitoroplasty. There are 3 different clitoroplasty procedures: clitorectomy, clitoral recession, and reduction clitoroplasty. Reduction clitoroplasty with preservation of the neurovascular bundle is considered superior in terms of formation of the external genitals and sensation. However, the disadvantages are that detachment of the neurovascular bundle from the clitoral shaft is difficult and that there is a high possibility of sensory and blood flow disorders in the clitoris. In an attempt to achieve safe and reliable surgical manipulation, we used a surgical microscope (OPMI 6-SDFC, Carl Zeiss Surgical GmbH, magnification ×8) to detach the neurovascular bundle from the clitoral shaft in our 2 patients. Our impression is that our efforts were extremely effective. Furthermore, our experience leads us to believe that the procedure for neurovascular bundle detachment required in reduction clitoroplasty is not particularly difficult if performed with a surgical microscope by a plastic surgeon who regularly performs microsurgery. Because the procedure can be performed simply and safely, we believe that reduction clitoroplasty with preservation of the neurovascular bundle is the best overall of the 3 clitoroplasty procedures.

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I previously described the case of a 19 year-old female with severe mental retardation, developmental retardation, microcephalus, short stature, bilateral microphthalmia, ptosis and blepharophimosis¹. Now, I present clinical descriptions of her half-siblings, who have a different father. Subtelomeric fluorescence in situ hybridization (FISH) analysis of the proband demonstrated 5q terminal trisomy and 14q terminal monosomy. I presume that her mother harbors a balanced translocation between the terminal of chromosome 5q and 14q. I suggest that familial cases of mental retardation and dysmorphic features should be screened for terminal chromosomal abnormalities by FISH or comparative genomic hybridization (CGH), even if G-banding analysis or high-resolution chromosome analysis is normal.

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