Internal Risk Factors for Low Back Pain in Pole Vaulters and Decathletes: A Prospective Study.

BACKGROUND: Pole vaulters and decathletes frequently experience several types of injuries to their lower back, often resulting in mechanical low back pain (LBP). However, the risk factors for the occurrence of LBP in these athletes have not been defined. PURPOSE: To determine the physical factors that relate to LBP occurrence for collegiate pole vaulters and decathletes. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: We observed 31 pole vaulters and decathletes for 1 year. At the start of the observation period, isokinetic flexion and extension muscle strength of the knee and hip joints were recorded along with active and passive range of motion (ROM) and muscle tightness. Participants were then divided into 2 groups using the median value of each measurement: those below the median (low group) and those above the median (high group). The log-rank test was used to compare LBP occurrence between the low group and high group for all measurements. Multivariate regression analyses were thereafter applied using the Cox proportional hazards regression. RESULTS: Log-rank tests revealed a statistically significant change in the survival curve for the occurrence of LBP in the participants with chronic LBP (P = .037), the low group for hip flexion peak torque per body weight on the non-takeoff leg (P = .047), and the low group for passive hip flexion angle on both legs (takeoff leg: P = .034; non-takeoff leg: P = .023). In addition, log-rank tests revealed a statistically significant change in the survival curve for the occurrence of LBP in the low group for passive hip extension angle on the takeoff leg only for the participants without chronic LBP (P = .014). CONCLUSION: It may be necessary to acquire sufficient ROM and hip flexion to prevent LBP occurrence in pole vaulters and decathletes.

Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium.

The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at ≥20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H.

Japanese pediatric guideline for the treatment and management of bronchial asthma 2012.

A new version of the Japanese pediatric guideline for the treatment and management of bronchial asthma was published in Japanese at the end of 2011. The guideline sets the pragmatic goal for clinicians treating childhood asthma as maintaining a "well-controlled level" for an extended period in which the child patient can lead a trouble-free daily life, not forgetting the ultimate goal of obtaining remission and/or cure. Important factors in the attainment of the pragmatic goal are: (i) appropriate use of anti-inflammatory drugs; (ii) elimination of environmental risk factors; and (iii) educational and enlightening activities for the patient and caregivers regarding adequate asthma management in daily life. The well-controlled level refers to a symptom-free state in which no transient coughs, wheezing, dyspnea or other symptoms associated with bronchial asthma are present, even for a short period of time. As was the case in the previous versions of the guideline, asthmatic children younger than 2 years of age are defined as infantile asthma patients. Special attention is paid to these patients in the new guideline: they often have rapid exacerbation and easily present chronic asthmatic conditions after the disease is established.

Analysis of long-term stored plasma samples for investigation into the pathophysiology of vibration-induced white finger: preliminary results.

Blood samples were collected 25 yr ago from hand-arm vibration syndrome patients with vibration-induced white finge/VWF (VWF+ group) and without it (VWF- group), and healthy controls (n=12 in each group), and stored at -80 °C. The subjects provided venous blood twice: at baseline, and after cold exposure at 7 °C for 25 min. Blood specimens were analyzed for plasma endothelin-1 (ET-1) by an enzyme-linked immunosorbent assay. Baseline concentration of plasma ET-1 was found to be significantly larger in the VWF- group than the control group, whereas no such difference was observed for the VWF+ group. However, the %change was larger in the VWF+ group (107.73 ± 30.49%) than the other two groups, and more subjects in the VWF+ group showed the maximum increase in ET-1 than the other two groups. In conclusion, ET-1 appears to have a role in the pathophysiology of VWF.

Neurogenic airway microvascular leakage induced by toluene inhalation in rats.

Toluene is a representative airborne occupational and domestic pollutant that causes eye and respiratory tract irritation. We investigated whether a single inhalation of toluene elicits microvascular leakage in the rat airway. We also evaluated the effects of CP-99,994, a tachykinin NK(1) receptor antagonist, and ketotifen, a histamine H1 receptor antagonist with mast cell-stabilizing properties, on the airway response. The content of Evans blue dye that extravasated into the tissues was measured as an index of plasma leakage. Toluene (18-450 ppm, 10 min) concentration-dependently induced dye leakage into the trachea and main bronchi of anesthetized and mechanically ventilated rats. Toluene at concentrations of ≥ 50 and ≥ 30 ppm caused significant responses in the trachea and main bronchi, respectively, which both peaked after exposure to 135 ppm toluene for 10 min. This response was abolished by CP-99,994 (5 mg/kg i.v.), but not by ketotifen (1mg/kg i.v.). Nebulized phosphoramidon (1 mM, 1 min), a neutral endopeptidase 24.11 inhibitor, significantly enhanced the response induced by toluene (135 ppm, 10 min) compared with nebulized 0.9% saline (1 min). These results show that toluene can rapidly increase airway plasma leakage that is predominantly mediated by tachykinins endogenously released from airway sensory nerves. However, mast cell activation might not be important in this airway response.

The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children.

BACKGROUND: Cow's milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, α-lactalbumin and ß-lactoglobulin in cow's milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness. METHODS: Eighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n = 61) or non-CMA (n = 22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP®. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized). RESULTS: The CMA group had significantly higher levels of milk-, casein- and ß-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kUA/L corresponding to 100% specificity. All but one of the CMA children aged > 5 years had casein-sIgE levels > 6.6 kUA/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children. CONCLUSIONS: High levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.

Proliferation of sensory C-fibers and subsequent neurogenic inflammation in rat airway induced by inhaled lipopolysaccharide.

Lipopolysaccharide (LPS) is associated with the development and exacerbation of airway inflammation. Increases in innervation of sensory C-fibers and tachykinin receptors, which mainly involve overproduction of neurotrophins such as nerve growth factor (NGF), may enhance neurogenic inflammation. Expression of NGF and its receptors in rat lungs is known to decline with age. We examined whether inhaled LPS causes proliferation of sensory C-fibers, increased expression of tachykinin receptors and subsequent enhancement of neurogenic inflammation in the airways of preweaning rats. Wistar male rats aged 2 weeks inhaled aerosolized LPS derived from Escherichia coli (0.1mg/ml) for 30 min. Evans blue dye leakage into the trachea induced by gaseous formaldehyde or intravenous capsaicin was measured as an index of tachykinin NK1 receptor-mediated vascular permeability. Expression of substance P-immunoreactive nerves, tachykinin NK1 receptors, tumor necrosis factor (TNF)-α and NGF in the trachea was also assessed immunohistochemically. Neurogenic plasma leakage in the trachea increased significantly between 7 and 21 days after LPS inhalation. Expression of TNF-α, NGF, substance P-immunoreactive nerves and tachykinin NK1 receptors was enhanced, peaking at 28 h, 7 days, 14 days and 14 days after LPS inhalation, respectively. Pretreatment with infliximab, a blocking antibody for TNF-α, almost completely abolished the airway changes seen after LPS inhalation. In conclusion, inhaled LPS increased innervation of sensory C-fibers and expression of tachykinin NK1 receptors in the airway, probably resulting in enhancement of neurogenic airway inflammation. These airway responses may be caused by overproduction of neurotrophins including NGF, mainly through a TNF-α-mediated pathway.

Staphylococcal enterotoxin B causes proliferation of sensory C-fibers and subsequent enhancement of neurogenic inflammation in rat skin.

BACKGROUND: Staphylococcal enterotoxin B (SEB) may be associated with the exacerbation of atopic dermatitis. We investigated whether SEB causes proliferation of sensory C-fibers and subsequent enhancement of plasma leakage induced by sensorineural stimulation in rat skin. METHODS: SEB was applied intracutaneously to the abdomen of preweaning and adult rats. Evans blue dye leakage into the skin induced by topical 10% formalin was measured as an index of neurogenic skin vascular permeability. Local expression of substance P, tachykinin NK1 receptors, and nerve growth factor was assessed immunohistochemically. In addition, we assessed the effects of topical tacrolimus on these skin responses induced by SEB. RESULTS: Increased neurogenic skin plasma leakage was seen 7 days after SEB treatment in 2 different age groups. Innervation of substance P-immunoreactive nerves and expression of tachykinin NK1 receptors and nerve growth factor were also promoted by SEB, peaking at 7 days, 7 days, and 56 h after SEB treatment, respectively. Tacrolimus markedly inhibited these skin changes. CONCLUSIONS: SEB increased the innervation of sensory C-fibers and tachykinin NK1 receptors in rat skin, probably because of upregulated production of neurotrophins, including nerve growth factor, leading to enhancement of neurogenic skin inflammation. T cell activation induced by SEB may initiate these changes.

Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury.

BACKGROUND/AIMS: It remains elusive whether there is a crosstalk between Smad and mitogen-activated protein kinases (MAPKs) and whether it regulates cyclosporine A (CyA)-induced apoptosis in renal proximal tubular cells (RPTCs). METHODS: The effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western blotting or immunofluorescence) and apoptosis (determined by Hoechst 33258 staining) was examined in HK-2 cells. RESULTS: CyA induced apoptosis at 24 h and nuclear translocation of phosphorylated (p)-Smad2/3 at 3 h, which was continued till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till 24 h, and of p-p38MAPK at 1-6 h, which returned to control level at 12 h. CyA did not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190, deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth factor (EGF) activated ERK and p38MAPK but not JNK. EGF-induced activation of MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. CONCLUSION: Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates apoptosis in CyA-induced RPTC injury.

[Analysis of the risk factors to persistent milk allergy].

BACKGROUND: We have evaluated the prognosis of milk allergy and the related factors. METHODS: Patients with milk allergy (n=60) who had initially visited our hospital before 2 years old were recruited for the chart review. The ability of milk intake (> 30 ml) at the age of 5 years and the related clinical factors were evaluated. RESULTS: There were 33 patients (55%) who remained allergic to milk (allergic group) and 27 patients (45%) who could consume at least 30 ml of milk (small amount of milk intake group) by the age of 5 years. The small amount of milk intake group had a history of isolated skin symptoms after ingestion of milk more frequently than the allergic group. On the other hands, the allergic group experienced significantly higher rate of respiratory and gastrointestinal symptoms. Milk-specific IgE antibodies were examined repeatedly in each patient, and the IgE titers were significantly decreased by age in the small amount of milk intake group. In the allergic group, however, the maximum milk-specific IgE titers in each patient were significantly higher than those in the small amount of milk intake group, and after significant increase from the age of 0 to 1 years, the IgE titers did not decrease until the age of 3 years. CONCLUSIONS: Respiratory and gastrointestinal symptoms followed by milk intake and persistent high milk-specific IgE titers were associated with persistent milk allergy.

Alteration in airway microvascular leakage induced by sensorineural stimulation in rats exposed to inhaled formaldehyde.

Inhaled formaldehyde can rapidly produce microvascular leakage in the airway through stimulation of tachykinin NK1 receptors by tachykinins released from sensory nerves. Tachykinin NK1 receptors are known to be internalized in the cytoplasm after being stimulated, thus leading to transient attenuation of their action. We investigated time changes in airway microvascular leakage during formaldehyde inhalation for 45 min, and whether pre-inhalation of formaldehyde (5 ppm, 30 min) decreases the responses induced by subsequent inhaled formaldehyde (5 ppm, 15 min), intravenous capsaicin (75 µg/kg) and intravenous substance P (10 µg/kg) in rat airway. Evans blue dye content extravasated into the tissues was measured as an index of plasma leakage. Formaldehyde rapidly produced dye leakage in the airway, a response that ended within 15 min after the start of formaldehyde inhalation. Pre-inhalation of formaldehyde markedly decreased the responses induced by formaldehyde and capsaicin, but not substance P. However, dye leakage induced by formaldehyde was significantly enhanced by formaldehyde inhalation 20 h earlier. Our results suggest that tachyphylaxis in neurogenic airway microvascular leakage seen after formaldehyde inhalation may be due to impairment of tachykinin release from sensory nerves or decreases in tachykinins within sensory nerves. However, desensitization of tachykinin NK1 receptors was unlikely to be important in the tachyphylactic response.

[Health effects of formaldehyde, as an indoor air pollutant].

Formaldehyde is an important chemical used widely by industry in numerous household products. Therefore, when room ventilation is inadequate, formaldehyde may stagnate in rooms and adversely affect the health of inhabitants. Exposure to formaldehyde in living space has been found to be associated with asthma and 'sick house syndrome' (health disturbances induced by chemical contaminants in domestic environments). In addition, formaldehyde exposure among medical students and teachers who dissect cadavers in the gross anatomy laboratory likely causes a health problem. Avoidance of formaldehyde exposure can reduce the incidence and severity of ill-health conditions, although the ability of low concentrations of formaldehyde to trigger mechanisms contributing to them is still debated. Setting appropriate exposure limits for formaldehyde as an indoor environmental pollutant requires further quantitative and predictive evaluation of its health effects.

Japanese pediatric guidelines for the treatment and management of bronchial asthma 2008.

Abstract The fourth version of the Japanese Pediatric Guidelines for the Treatment and Management of Bronchial Asthma 2008 (JPGL 2008) was published by the Japanese Society of Pediatric Allergy and Clinical Immunology in December 2008. In JPGL 2008, the recommendations were revised on the basis of the JPGL 2005. The JPGL 2008 is different to the Global Initiative for Asthma guideline in that it contains the following items: a classification system of asthma severity; recommendations for long-term management organized by age; a special mention of infantile asthma; and an emphasis on prevention and early intervention. Here we show a summary of the JPGL 2008 revising our previous report concerning JPGL 2005.

Development of mechanisms associated with neurogenic-mediated skin inflammation during the growth of rats.

Neurogenic-mediated inflammation may be associated with several inflammatory skin diseases including atopic dermatitis. However, age-dependent differences in neurogenic-mediated skin responses are not fully understood. We compared skin plasma leakage in rats aged 2 and 8 wk, which was induced by topical capsaicin, topical formalin, and intracutaneous substance P, whose effects are mediated via tachykinin NK1 receptors. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. Capsaicin, formalin, and substance P caused a skin response in a dose-dependent manner in both age groups. However, the skin response was much greater in adults than in pups. In addition, the localization of sensory C-fibers and tachykinin NK1 receptors in the skin was investigated by immunofluorescent staining with antisubstance P and antitachykinin NK1 receptor antibodies, respectively. Substance P-immunoreactive nerves were detected throughout the dermis and tachykinin NK1 receptors were mainly detected in blood vessel walls in the dermis in both age groups. However, they were more sparsely distributed in pups. In conclusion, the weak neurogenic-mediated skin inflammation in pups is probably because of immature neural mechanisms associated with skin inflammation such as reduced innervation of sensory C-fibers and low expression of tachykinin NK1 receptors.

Tacrolimus hydrate ointment inhibits skin plasma extravasation in rats induced by topical m-xylene but not capsaicin.

Tacrolimus ointment is used to treat various chronic inflammatory skin diseases. However, the effect of this ointment on acute neurogenic inflammation in the skin remains to be fully elucidated. Topical capsaicin and m-xylene produce tachykinin release from sensory nerves in the skin, resulting in skin plasma leakage. We investigated the effect of tacrolimus ointment (0.1%) on skin microvascular leakage induced by topical capsaicin (10 mM) and m-xylene (neat), and intracutaneous compound 48/80 (c48/80) (10 microg/ml, 50 microl/site) in two groups of rats pretreated with excessive capsaicin or its vehicle. The amount of leaked Evans blue dye reflected skin plasma leakage. Capsaicin, m-xylene or c48/80 was applied to the shaved abdomens of rats 8 h after topical application of tacrolimus ointment or its base. Desensitization with capsaicin reduced the skin response to capsaicin and m-xylene by 100% and 65%, respectively, but not to c48/80. Tacrolimus ointment significantly inhibited the skin response induced by m-xylene and c48/80, regardless of pretreatment with capsaicin. However, topical tacrolimus did not influence the skin response induced by capsaicin. We also evaluated whether topical capsaicin and m-xylene, and intracutaneous c48/80 cause mast cell degranulation in skin treated with tacrolimus. Mast cell degranulation was microscopically assessed. Topical tacrolimus only significantly suppressed degranulation induced by m-xylene and c48/80. Our data shows that tacrolimus ointment partially inhibits plasma leakage and mast cell degranulation in rat skin induced by m-xylene and c48/80 but not capsaicin, suggesting that the inhibitory effect is not associated with a reduction in neurogenic-mediated mechanisms.

Allergic bronchopulmonary aspergillosis in a 2-year-old asthmatic boy with immune dysregulation, polyendocrinopathy, enteropathy, X-linked.

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is caused by impaired function of CD4(+)CD25(+) regulatory T cells that play an important role in controlling exaggerated Th2 responses. The pathogenesis of allergic bronchopulmonary aspergillosis (ABPA) appears to be closely associated with the Th2 response. We report the first case of ABPA in a 2-year-old asthmatic boy with IPEX, this being an unusually young age for the development of ABPA.

[Improved capability of a revised test kit, FASTKIT ELISA version II (Egg), to detect heated proteins of egg white but not egg yolk].

BACKGROUND: A kit, FASTKIT ELISA version II (Egg) (Nippon Meat Packers) is an enzyme-linked immunosorbent assay kit for detecting hen's egg proteins in foodstuffs. This kit is an enhanced version of FASTKIT ELISA (Egg) with a greater efficiency in terms of extraction of egg proteins from heated foodstuffs. However, the property of this kit remains to be fully elucidated. METHODS: Using this new kit, we measured the amount of egg proteins in unheated or heated (140 degrees C or 180 degrees C, 20 min) homemade cookies containing whole egg, egg white or egg yolk. RESULTS: The capability for detection of unheated or heated (140 degrees C or 180 degrees C) whole egg proteins was similar. In addition, there was no significant difference in the detectability between heated (140 degrees C) whole egg and egg white proteins. However, unheated or heated (140 degrees C or 180 degrees C) egg yolk proteins were not sufficiently measured by this kit. CONCLUSION: Our data suggest that this new kit is significantly improved for detection of heated egg white proteins as compared to that of old version, but not sufficient for detection of egg yolk proteins.

Differential effects of topically applied formalin and aromatic compounds on neurogenic-mediated microvascular leakage in rat skin.

Various volatile organic compounds (VOCs) act as a causative agent of skin inflammation. We investigated the effect of topical application of several VOCs and formalin on microvascular leakage in rat skin. We tested capsaicin, which is a reagent that specifically causes the skin response via endogenously released tachykinins. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. After shaving the abdomen, we applied formalin, m-xylene, toluene, styrene, benzene, ethylbenzene, acetone, diethyl ether, hexane, heptane, cyclohexane and capsaicin to the skin. At 40min after application, skin samples were collected. Among all of the VOCs tested, all of the aromatic compounds significantly produced skin microvascular leakage that was similar to formalin and capsaicin. We also investigated the skin responses seen after the intravenous administration of CP-99,994 (1.5 or 5mg/kg), which is a tachykinin NK1 receptor antagonist, ketotifen (1 or 3mg/kg), which is a histamine H1 receptor antagonist that stabilizes the mast cells, and the topical application of capsazepine (22.5 or 50mM), which is the transient receptor potential vanilloid 1 (TRPV1) antagonist. The response induced by formalin and capsaicin was completely inhibited by CP-99,994. On the other hand, the antagonist partially reduced the response induced by m-xylene, toluene and styrene by 39%, 50% and 46%, respectively. Capsazepine and ketotifen did not alter the response induced by formalin or any of the aromatic compounds. Like capsaicin, formalin and the aromatic compounds at least partially caused skin microvascular leakage, which was due to tachykinin NK1 receptor activation related to the release of tachykinins from the sensory nerve endings. However, it is unlikely that mast cells and TRPV1 play an important role in the skin response.

[Open food challenge with milk, egg white and wheat].

BACKGROUND: A method for open food challenge test to determine food allergy has not been established in an evidence-based manner. METHODS: We conducted an analysis of 438 open food challenges of raw milk (n=133, mean age 2.7+/-1.9 years), boiled egg white (n=216, 2.8+/-2.1 years) or udon noodles (n=89, 2.7+/-1.7 years) for the patients aged 1 year or more. Doses were increased (trace amounts, 1 g, 2 g, 5 g, 10 g, 20-30 g) every 20 minutes. RESULTS: In total, 151 (38.5%) of food challenges were positive. The positive rates of milk, egg and wheat challenges were 35.8%, 42.4% and 33.3%, respectively. Of these, 76.2%, 32.5%, 27.8% and 0.7% had, respectively, skin, respiratory, gastrointestinal and cardiovascular symptoms. Although the prevalence of positive challenge increased with level of specific IgE, it did not correlate with the threshold amount of positive food challenge or the severity of symptoms. Among the challenge positive patients, 10.6% required injection of antihistamines, corticosteroids or adrenalines for the treatment of the symptoms. CONCLUSIONS: This challenge protocol seemed to be appropriate and safe.