Effects of Both Japanese-Style Dietary Patterns and Nutrition on Falling Incidents among Community-Dwelling Elderly Individuals: A Cross-Sectional Study.

Approximately 20% of the community-dwelling Japanese elderly (≥65 years) experience falling annually, with injury frequency rising with age. Increased nursing home admission/hospitalization risk influences healthy aging and QOL. Nutrition for musculoskeletal health is necessary, though the relationship of falling with nutritional status in the elderly is largely unknown. We investigated falling incidents and nutritional status, including a Japanese-style diet in a community-dwelling cohort. Using a cross-sectional design, 186 subjects (median age 83.0 years, males/females 67/119) were analyzed. Oral and systemic health conditions were assessed. A brief-type self-administered diet history questionnaire (BDHQ) was given for nutritional status. Analysis of covariance (adjusted for gender, age, BMI, articular disease/osteoporosis history, present tooth number, educational level) and the Japanese-Mediterranean diet (jMD) score adapted for Japan were used. The jMD score and falling incidents were significantly associated, with point increases related to a significantly decreased falling risk of 28% (OR: 0.72; 95%CI: 0.57−0.91). Of the 13 jMD food components, fish, eggs, and potatoes had a significant relationship with reduced falling, while significant associations of intake of animal protein, potassium, magnesium, zinc, and cholesterol (p < 0.05) were also observed. The results suggest that the jMD dietary pattern is an important factor for the prevention of falling incidents in elderly individuals.

The role of epidermal growth factor-like domain-related abnormalities, protein S Tokushima, and anti-protein S autoantibodies in pregnancy loss.

BACKGROUND: Protein S (PS) deficiency and autoantibodies that bind to PS (anti-PS) have been described in patients with adverse pregnancy outcomes, including pregnancy loss. PS Tokushima is a congenital abnormality of the second epidermal growth factor (EGF)-like domain, and anti-PS has been reported to recognize EGF-like domains. OBJECTIVES: We evaluated the role of PS Tokushima and anti-PS in patients with pregnancy loss. METHODS: Patients with recurrent early pregnancy loss (n = 324; group A), those with one or more mid-to-late pregnancy loss (n = 196; group B), and infertile women having no pregnancy loss (n = 650; group C) were screened for PS type II deficiency and anti-PS. Patients who were diagnosed with PS type II deficiency underwent genetic analysis for the detection of PS Tokushima. RESULTS: The incidence of patients with PS Tokushima was 1.85 %, 5.10 %, and 1.23 % in groups A, B, and C, respectively. The incidence of patients with PS Tokushima was significantly higher in group B (p = 0.0027) than in group C. The incidence of patients with anti-PS was 20.1 %, 23.0 %, and 19.2 % in groups A, B, and C, respectively. The incidence of patients with anti-PS was significantly higher in groups A (p = 0.0229), B (p = 0.0071), and C (p = 0.0288) than in previously reported healthy nonpregnant women (7.1 %, 4/56). CONCLUSIONS: Our data suggest that PS Tokushima is associated with mid-to-late pregnancy loss, while anti-PS are associated with recurrent early pregnancy loss, mid-to-late pregnancy loss, and infertility.

Anti-Factor XII Autoantibodies in Patients with Recurrent Pregnancy Loss Recognize the Second Epidermal Growth Factor-Like Domain.

Background Factor XII (FXII) deficiency and autoantibodies that bind to FXII (anti-FXII) have been described in patients with adverse pregnancy outcomes, including recurrent pregnancy loss. It has been reported that FXII functions not only as a coagulation protein but also as a growth factor. Objectives We studied the association between anti-FXII and the epidermal growth factor (EGF) system in patients with recurrent pregnancy loss. Patients/Methods We used synthetic peptides that span the second EGF-like domain in the heavy chain of FXII (EGF2) in inhibition and direct binding studies to determine if anti-FXII antibodies recognize EGF2. Furthermore, we examined whether anti-FXII antibodies, which recognize EGF2, also recognize recombinant EGF and heparin-binding EGF-like growth factor (HB-EGF). Results Among 100 patients with recurrent pregnancy loss, the plasma of 23 patients (23.0%) recognized the synthetic peptide ASQ41, which covers EGF2. Among the 23 anti-ASQ41-positive patients, plasma samples from 13 patients (56.5%) recognized the 22-residue segment C-terminal half of ASQ41. Among the 23 anti-ASQ41-positive patients, the plasma of 17 patients (73.9%) recognized recombinant human EGF. Affinity-purified anti-FXII antibodies, which recognize ASQ41, also recognized recombinant EGF family proteins such as EGF and HB-EGF. Conclusions The autoantibodies in patients with recurrent pregnancy loss recognized the EGF2 domain in FXII and other proteins of the EGF family. Since proteins in the EGF family play an important role in normal pregnancy, autoantibody-associated disruption of the EGF system may cause pregnancy loss.

Antigenic binding sites of anti-protein S autoantibodies in patients with recurrent pregnancy loss.

BACKGROUND: Protein S (PS) deficiency is a risk factor for adverse pregnancy outcomes including recurrent pregnancy loss. Several studies have shown that the presence of anti-PS autoantibodies (anti-PS) leads to an acquired PS deficiency. Hence, an epitope mapping study was conducted to know the pathogenesis of anti-PS in patients with recurrent pregnancy loss. METHODS: PS was treated with thrombin to divide the protein into γ-carboxyglutamic acid (Gla) domain and Gla-domain free PS. For the preparation of fragments of epidermal growth factor (EGF)-like domains (EGF1-4), PS was subjected to proteolysis using lysyl endopeptidase. The epitopes were identified in immunoblot. Whether anti-PS recognized EGF family proteins in anti-PS-positive patients was also examined. RESULTS: Anti-PS recognized Gla-domain free PS, especially the three fragments of EGF-like domains, EGF1-2, EGF3-4, and EGF1-4. Anti-PS recognized recombinant human EGF. Anti-PS and polyclonal antibodies to recombinant human EGF recognized PS in the absence of Ca2+ but not in the presence of Ca2+. In competitive inhibition studies, polyclonal antibodies to recombinant mouse EGF blocked anti-PS binding to PS in a concentration-dependent manner. CONCLUSIONS: These results suggest that anti-PS in patients with recurrent pregnancy loss recognize EGF-like domains in PS. Interestingly, anti-PS also recognized EGF family proteins. Anti-PS in patients with recurrent pregnancy loss may be associated with not only thrombophilia but also the disruption of the EGF system.

Resolution of dopamine agonist-resistant hyperprolactinemia by hysterectomy: a case report.

Prolactin-producing uterine leiomyomas are very rare. Although hyperprolactinemia rapidly improves after removal of such leiomyomas, no preoperative diagnostic test has been established for prolactin-producing uterine leiomyomas. A 45-year-old Japanese woman, gravida 3 para 3, was referred to our hospital for further examination of hyperprolactinemia resistant to a dopamine agonist. A pituitary prolactinoma was undetectable by brain magnetic resonance imaging. A bromocriptine loading test revealed an increased serum prolactin concentration after loading. Examination for the detection of an ectopic prolactinoma revealed a 9.0 cm diameter uterine leiomyoma that had measured 6.6 cm in diameter about six months before the first visit to our hospital. The hyperprolactinemia rapidly improved after hysterectomy. A prolactin-producing uterine leiomyoma should be considered as a possible cause of hyperprolactinemia resistant to dopamine agonists. Responsiveness to dopamine agonists; deterioration of hyperprolactinemia may be diagnostic for prolactin-producing uterine leiomyomas, although further research is required.

Steroid Pulse Therapy for De Novo Minimal Change Disease During Pregnancy.

BACKGROUND Nephrotic syndrome occurs very rarely, in only about 0.01%-0.02% of all pregnancies, and de novo minimal change disease during pregnancy is especially rare. Nephrotic syndrome and, especially, minimal change disease are highly responsive to steroids, and preterm labor may be avoidable if the maternal condition is improved with steroid therapy. Therefore, prompt diagnosis and proper management are critical to maternal and fetal outcome when severe proteinuria occurs during pregnancy. CASE REPORT A 30-year-old pregnant Japanese woman presented with systemic edema, oliguria, and severe proteinuria and hypoalbuminemia at 25 weeks of gestation, although she was normotensive. The patient had high urinary protein selectivity. Her illness was diagnosed as de novo nephrotic syndrome with high steroid responsiveness rather than pre-eclampsia. She began steroid pulse therapy the day after admission. Complete remission was confirmed after 3 weeks. The patient did not relapse during pregnancy and delivered a healthy male baby at 37 weeks of gestation. A renal biopsy at a relapse after delivery confirmed minimal change disease. CONCLUSIONS In pregnant women with de novo minimal change disease, serious maternal and/or fetal complications may occur if severe proteinuria and hypoalbuminemia are unabated for an extended time. Evaluation of urinary protein selectivity is noninvasive and useful for prediction of steroid responsiveness. Results of urinary protein selectivity can be obtained earlier than results of renal biopsy. Renal biopsy during pregnancy is not always necessary for initiation of steroid therapy. Rapid initiation of steroid pulse therapy may enable quicker achievement of remission and prevent serious perinatal complications.

Relationships among sense of coherence, oral health status, nutritional status and care need level of older adults according to path analysis.

AIM: Sense of coherence (SOC) is a measurement of ability of an individual to cope with psychological stress and remain in good health. The aim of the present study was to examine the relationships among SOC score, oral health status, nutritional status and care need level of older adults using path analysis. METHODS: We enrolled 53 older adults (17 men and 36 women) who were attending a day care service (mean age 80.4 ± 6.5 years). SOC was assessed using a 13-item, seven-scale instrument. Oral health status (number of present teeth, denture use) and nutritional status (assessed with Mini-Nutritional Assessment Short-Form) were also evaluated. Path analysis was used to examine the relationship of SOC with other related factors, including care need level. RESULTS: The mean SOC score was 57.0 ± 13.9. Mini-Nutritional Assessment Short-Form results showed that one participant (1.8%) was malnourished, 26 (49.1%) were at risk of malnutrition and 26 (49.1%) had normal nutritional status. Participants with high SOC scores showed a strong positive attitude, had a relatively large number of teeth, were in good nutritional condition and showed low care need levels. CONCLUSIONS: The present results showed that maintaining a high SOC level and good oral health help to reduce care need levels in older adults, and also prevent a worsening of their nutritional condition. Geriatr Gerontol Int 2017; 17: 2083-2088.

Study of local intracellular signals regulating axonal morphogenesis using a microfluidic device.

The establishment and maintenance of axonal patterning is crucial for neuronal function. To identify the molecular systems that operate locally to control axonal structure, it is important to manipulate molecular functions in restricted subcellular areas for a long period of time. Microfluidic devices can be powerful tools for such purposes. In this study, we demonstrate the application of a microfluidic device to clarify the function of local Ca2+ signals in axons. Membrane depolarization significantly induced axonal branch-extension in cultured cerebellar granule neurons (CGNs). Local application of nifedipine using a polydimethylsiloxane (PDMS)-based microfluidic device demonstrated that Ca2+ entry from the axonal region via L-type voltage-dependent calcium channels (L-VDCC) is required for branch extension. Furthermore, we developed a method for locally controlling protein levels by combining genetic techniques and use of a microfluidic culture system. A vector for enhanced green fluorescent protein (EGFP) fused to a destabilizing domain derived from E. coli dihydrofolate reductase (ecDHFR) is introduced in neurons by electroporation. By local application of the DHFR ligand, trimethoprim (TMP) using a microfluidic device, we were able to manipulate differentially the level of fusion protein between axons and somatodendrites. The present study revealed the effectiveness of microfluidic devices to address fundamental biological issues at subcellular levels, and the possibility of their development in combination with molecular techniques.

The Impact of Pediatrician Supply on Child Health Outcomes: Longitudinal Evidence from Japan.

OBJECTIVE: To investigate the effect of pediatrician supply on under-5 mortality over the period 2000-2010. DATA SOURCES: Multiple publicly available data sources were used. STUDY DESIGN: Japan's 366 "Secondary Tier of Medical Care Units" (STMCU) were used as study units. To evaluate the association between under-5 mortality and pediatrician supply, we explored time and area fixed-effects Poisson regression model. The following factors were introduced into the models as time-varying controls: (1) number of physicians other than pediatricians per total population except for under-5-year-old population, and (2) income per total population by year and STMCU. Extensive sensitivity analyses were conducted to assess robustness of results. PRINCIPAL FINDINGS: Pediatrician density was inversely associated with under-5 mortality. We estimated that a unit increase in pediatrician density was associated with a 7 percent (95 percent CI: 2-12 percent) reduction in the child mortality rate after adjustment for all other variables. The results were consistent and robust across all specifications tested. CONCLUSIONS: The results suggest that increasing human health resources can have positive effects on child health, even in settings where child mortality of less than 5 per 1,000 has been achieved.

Autoantibodies to Factor XII and Kininogen-Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation.

PROBLEM: Numerous studies have suggested that factor XII (FXII) deficiency, autoantibodies to FXII (anti-FXII), and antiphosphatidylethanolamine antibodies (aPE) are associated with recurrent pregnancy loss (RPL). aPE in RPL patients recognize the LDC27 peptide of kininogen domain 3. Anti-FXII in RPL patients recognizes the heavy chain of FXII, especially the amino-terminal sequences IPP30 peptide. Previous studies suggested that LDC27 and IPP30 are the responsible sites competing for the same binding site on platelets and inhibiting augmentation of thrombin-induced platelet aggregation. Our aim was to study the influence of antibodies to LDC27 and IPP30 on platelet aggregation. METHODS OF STUDY: In fifteen healthy volunteers, platelet aggregation induced by γ-thrombin in the presence or absence of antibodies to LDC27 and IPP30 was measured. Sixteen RPL patients who were positive for anti-FXII were measured for spontaneous small platelet aggregate (SSPA) formation. RESULTS AND CONCLUSIONS: Antibodies to LDC27 and IPP30 markedly increased aggregation of normal platelets stimulated by γ-thrombin. Augmentation of SSPA formation was more frequent in the patients with RPL who were positive for anti-FXII than in the control group (P = 0.003). This study strongly supports the hypothesis that aPE and anti-FXII may cause RPL due to disruption of the normal antithrombotic effects of kininogens and FXII.

Correlation between pediatrician supply and public health in Japan as evidenced by vaccination coverage in 2010: secondary data analysis.

BACKGROUND: In industrialized countries, assessment of the causal effect of physician supply on population health has yielded mixed results. Since the scope of child vaccination is an indicator of preventive health service utilization, this study investigates the correlation between vaccination coverage and pediatrician supply as a reflection of overall pediatric health during a time of increasing pediatrician numbers in Japan. METHODS: Cross-sectional data were collected from publicly available sources for 2010. Dependent variables were vaccination coverage for measles and diphtheria, pertussis, and tetanus (DPT) by region. The primary predictor of interest was number of pediatricians per 10,000-child population (pediatrician density) at the municipality level. Multivariate logistic regression models were used to estimate associations of interest, conditional on a large range of demographic and infrastructure-related factors as covariates, including non-pediatric physician density, total population, per capita income, occupation, unemployment rate, prevalence of single motherhood, number of hospital beds per capita, length of roads, crime rate, accident rate, and metropolitan area code as urban/rural status. The percentage of the population who completed college-level education or higher in 2010 was included in the model as a proxy for education level. RESULTS: Pediatrician density was positively and significantly associated with vaccination coverage for both vaccine series. On average, each unit of pediatrician density increased odds by 1.012 for measles (95% confidence interval, 1.010-1.015) and 1.019 for DPT (95% confidence interval, 1.016-1.022). CONCLUSIONS: Policies increasing pediatrician supply contribute to improved preventive healthcare services utilization, such as immunizations, and presumably improved child health status in Japan.

Evaluating the effect of Japan's 2004 postgraduate training programme on the spatial distribution of physicians.

BACKGROUND: In 2004, the Japanese government permitted medical graduates for the first time to choose their training location directly through a national matching system. While the reform has had a major impact on physicians' placement, research on the impact of the new system on physician distribution in Japan has been limited. In this study, we sought to examine the determinants of physicians' practice location choice, as well as factors influencing their geographic distribution before and after the launch of Japan's 2004 postgraduate medical training programme. METHODS: We analyzed secondary data. The dependent variable was the change in physician supply at the secondary tier of medical care in Japan, a level which is roughly comparable to a Hospital Service Area in the US. Physicians were categorized into two groups according to the institutions where they practiced; specifically, hospitals and clinics. We considered the following predictors of physician supply: ratio of physicians per 1,000 population (physician density), age-adjusted mortality, as well as measures of residential quality. Ordinary least-squares regression models were used to estimate the associations. A coefficient equality test was performed to examine differences in predictors before and after 2004. RESULTS: Baseline physician density showed a positive association with the change in physician supply after the launch of the 2004 programme (P-value < .001), whereas no such effect was found before 2004. Urban locations were inversely associated with the change in physician supply before 2004 (P-value = .026), whereas a positive association was found after 2004 (P-value < .001). Urban location and area-level socioeconomic status were positively correlated with the change in hospital physician supply after 2004 (P-values < .001 for urban centre, and .025 for area-level socioeconomic status), even though in the period prior to the 2004 training scheme, urban location was inversely associated with the change in physician supply (P-value = .015) and area-level socioeconomic status was not correlated. CONCLUSION: Following the introduction of the 2004 postgraduate training programme, physicians in Japan were more likely to move to areas with already high physician density and urban locations. These changes worsened regional inequality in physician supply, particularly hospital doctors.

Validation of predictive equations for resting energy expenditure in Japanese pediatric Crohn's disease patients: preliminary study.

BACKGROUND: Predictive equations are often used to estimate resting energy expenditure (REE). Determining the appropriate equation for different patient types, however, remains inconclusive, as in the case of Japanese children with Crohn's disease (CD). The aim of this study was to identify an appropriate predictive equation for measuring REE in Japanese children with CD. METHODS: Twelve Japanese children with CD managed at the National Center for Child Health and Development in Tokyo, Japan, were studied. REE (kcal/day) was measured using indirect calorimetry. The predictive equations used were the Japanese Dietary Reference Intakes (2010), the Schofield equation, the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) equation and the Cunningham equation. Difference between predicted and measured REE was analyzed on Bland-Altman plot. RESULTS: Japanese Dietary Reference Intakes (2010) had the smallest difference between predicted and measured REE. Weight was the primary predictor of REE on multiple regression analysis. As well, Japanese Dietary Reference Intakes (2010) had the highest ratio of weight to predicted REE (98.5%). CONCLUSIONS: Of the four equations, Japanese Dietary Reference Intakes (2010) appeared to be the most practical and accurate predictive equation for REE in Japanese children with CD.

Pediatricians' practice location choice-Evaluating the effect of Japan's 2004 postgraduate training program on the spatial distribution of pediatricians.

OBJECTIVES: To explore determinants of change in pediatrician supply in Japan, and examine impacts of a 2004 reform of postgraduate medical education on pediatricians' practice location choice. METHODS: Data were compiled from secondary data sources. The dependent variable was the change in the number of pediatricians at the municipality ("secondary tier of medical care" [STM]) level. To analyze the determinants of pediatrician location choices, we considered the following predictors: initial ratio of pediatricians per 1000 children under five years of age (pediatrician density) and under-5 mortality as measures of local area need, as well as measures of residential quality. Ordinary least-squares regression models were used to estimate the associations. A coefficient equality test was performed to examine differences in predictors before and after 2004. Basic comparisons of pediatrician coverage in the top and bottom 10% of STMs were conducted to assess inequality in pediatrician supply. RESULTS: Increased supply was inversely associated with baseline pediatrician density both in the pre-period and post-period. Estimated impact of pediatrician density declined over time (P = 0.026), while opposite trends were observed for measures of residential quality. More specifically, urban centers and the SES composite index were positively associated with pediatrician supply for the post-period, but no such associations were found for the pre-period. Inequality in pediatrician distribution increased substantially after the reform, with the best-served 10% of communities benefitting from five times the pediatrician coverage compared to the least-served 10%. CONCLUSIONS: Residential quality increasingly became a function of location preference rather than public health needs after the reform. New placement schemes should be developed to achieve more equity in access to pediatric care.

The impact of Japan's 2004 postgraduate training program on intra-prefectural distribution of pediatricians in Japan.

OBJECTIVE: Inequity in physician distribution poses a challenge to many health systems. In Japan, a new postgraduate training program for all new medical graduates was introduced in 2004, and researchers have argued that this program has increased inequalities in physician distribution. We examined the trends in the geographic distribution of pediatricians as well as all physicians from 1996 to 2010 to identify the impact of the launch of the new training program. METHODS: The Gini coefficient was calculated using municipalities as the study unit within each prefecture to assess whether there were significant changes in the intra-prefectural distribution of all physicians and pediatricians before and after the launch of the new training program. The effect of the new program was quantified by estimating the difference in the slope in the time trend of the Gini coefficients before and after 2004 using a linear change-point regression design. We categorized 47 prefectures in Japan into two groups: 1) predominantly urban and 2) others by the definition from OECD to conduct stratified analyses by urban-rural status. RESULTS: The trends in physician distribution worsened after 2004 for all physicians (p value<.0001) and pediatricians (p value = 0.0057). For all physicians, the trends worsened after 2004 both in predominantly urban prefectures (p value = 0.0012) and others (p value<0.0001), whereas, for pediatricians, the distribution worsened in others (p value = 0.0343), but not in predominantly urban prefectures (p value =0.0584). CONCLUSION: The intra-prefectural distribution of physicians worsened after the launch of the new training program, which may reflect the impact of the new postgraduate program. In pediatrics, changes in the Gini trend differed significantly before and after the launch of the new training program in others, but not in predominantly urban prefectures. Further observation is needed to explore how this difference in trends affects the health status of the child population.

Relationship between prevalence of childhood obesity in 17-year-olds and socioeconomic and environmental factors: prefecture-level analysis in Japan.

To investigate the association between childhood obesity and neighborhood-level socio-economic and environmental factors in Japan. The prevalence of childhood obesity in 2008 was obtained from annual reports of the School Health Survey. The following 12 factors were publicly available: income per person, ratio of people completing up to college or university education, population density, total length of roads per square kilometer, number relative to the population of food and drink stores, restaurants, large-scale retail stores, convenience stores, passenger cars, traffic accidents, criminal offenses, and death by accidents. The ratio of people completing up to college or university education was inversely associated with obesity in boys and girls. No association was found between obesity and the other factors examined. An inverse association was shown between educational level and childhood obesity in both boys and girls. Further studies integrating associations between childhood obesity and neighborhood-level factors are needed.

Does fever phobia cross borders? The case of Japan.

BACKGROUND: Undue parental fear of fever in children was termed "fever phobia" by Schmitt following a survey in the USA in 1980. In 2000, Crocetti et al. conducted the same survey and concluded that fever phobia existed even 20 years later. In this study, we explore differences in fever phobia between these two US populations and a Japanese sample, and determine whether parents of a single child or those whose child was previously hospitalized or had a febrile seizure report greater anxiety about fever. METHODS: A questionnaire was distributed to parents of children who visited a pediatric outpatient clinic in Juntendo University Nerima Hospital between 19 and 30 November 2007. RESULTS: Data was obtained from 211 parents who agreed to participate in the study. Compared with much smaller proportions reported in the two previous studies, 62% of caregivers considered a temperature below 37.8°C to be a fever, although less than half of parents reported that they were "very worried" about fever. Over 90% identified doctors and nurses as their primary information source. In contrast to 7% of parents in the US studies, almost no parents reported that temperatures could rise to or above 43.3°C if fever was left untreated; however, 63% of parents stated that they would visit a hospital. CONCLUSIONS: Fever phobia exists on both sides of the border, and while caregivers in Japan appear to have a more accurate understanding of fever, they are more likely to rely on health-care professionals to manage the condition.

Does the pediatricians' work setting or years of experience influence febrile seizure education?

INTRODUCTION: A febrile seizure is a benign condition. However, for parents, witnessing their child's FS can cause excessive anxiety. It is therefore important for pediatricians to provide appropriate information in order to reduce anxiety. In this study, we analyze whether work setting and years of experience influence the explanations given to caregivers. METHODS: Questionnaires were mailed to members of the Japan Pediatric Society, Tokyo Chapter (n=1 870). The Mantel-Haenszel test was used for dichotomous variables. Differences for continuous variables were evaluated at 95% confidence intervals. RESULTS: A total of 482 pediatricians participated. There were no significant differences in responses to any questions according to work setting. Responders with less than 20 years of experience reported a higher prevalence of febrile seizures than those in the more experienced group. Compared to the experienced group, more responders with less than 20 years of experience stated that they would administer antiepileptic prophylaxis and advise parents not to use antipyretics, and indicated that they did not know the FS treatment guidelines. CONCLUSION: The findings suggest the importance of promoting a better understanding of FS among less-experienced pediatricians and encouraging adherence to the guidelines to maintain a consistent level of support for parents and caregivers.

Immunohistochemical analysis of pyloric gland adenomas using a series of Mucin 2, Mucin 5AC, Mucin 6, CD10, Ki67 and p53.

A pyloric gland adenoma (PGA) of the stomach was first described in a book chapter in 1976 by Kurt Elster and has been rarely reported in the literature. We expanded the current immunohistochemical data of these adenomas in a detailed series to further analyse the immunhistochemical status of PGA. From 60 patients with PGA with and without adenocarcinomas of the gastrointestinal tract, an immunhistochemical panel of Mucin 2, Mucin 5AC, Mucin 6, CD10, Ki67 and p53 was used to define the expression of these markers. All PGA were positive for Mucin 6 (deep mucoid glands), which they express over the whole lesion up to the surface. Mucin 5AC expression varies from case to case. A transition from gastric to intestinal differentiation can be observed focally as depicted by Mucin 2 and CD10 in 65% of the cases. The gastric corpus mucosa of elderly patients with either Helicobacter pylori gastritis or autoimmune gastritis is highly affected. Almost 47% of all PGA already underwent malignant transformation into adenocarcinoma. Significant immunohistochemical differences could be detected between PGA with and without adenocarcinoma regarding ki67 and p53. The diagnosis of PGA can be confirmed immunohistochemically by staining against apomucin 6 and apomucin 5AC. Focal intestinal differentiation supports the hypothesis that gastric adenocarcinomas can initially develop from carcinomas of the gastric type and transform into intestinal type later on. The high frequency of malignant transformation of PGA underlines its high potential for invasive malignancy.