School Anxiety in Children and Adolescents with Chronic Pain.

Anxiety is highly prevalent in pediatric chronic pain. This comorbidity has been explained by the presence of shared mechanisms underlying the development and maintenance of chronic pain and anxiety. Accumulating evidence demonstrates that school is a significant source of anxiety among youth with chronic pain and that anxiety contributes to school-related functional impairment in this population. This article reviews the cooccurrence of pediatric chronic pain and anxiety, identifies unique sources of heightened school anxiety among youth with chronic pain, and describes current approaches for assessing anxiety in pediatric pain settings. Highlighted by this review is the absence of a comprehensive evidence-based approach for assessing school anxiety in pediatric chronic pain. Given the psychometric limitations inherent to gathering data from a single source, recommendations for advancing measurement methods are provided. Novel approaches may be needed to shed more light on the way in which school anxiety is experienced in pediatric chronic pain.

Human sperm DNA damage inhibition and antioxidant activity of T. arjuna bark: an in vitro study.

Complimentary or natural antioxidant type of alternative medicine is developed worldwide to treat male infertility. The aim of this study is to the extraction of T. arjuna bark and activity against human sperm DNA damage in asthenoteratospermic smoker's subjects-an in vitro study. All preliminary and antioxidant assays (DPPH, H2O2, and total antioxidant, reducing power activity) were done. T. arjuna bark metal analysis was done with AAS. On the other hand, patients were asked to fill a direct questionnaire about smoking history; 25 infertile smokers were identified as asthenoteratospermic; 34 fertile non-smokers (control) were assessed for semen parameters by CASA, seminal plasma Zinc analysis by AAS, DNA fragmentation by colorimetric method and semen genomic DNA damage inhibition by modified non-enzymatic salting out extraction method. Most of the antioxidants are highly present in the aqueous extract; meanwhile, the major content in this extract is zinc 16 µg/g (Ca = 0.5 µg/g; Se = 2.2 µg/g and Mg = 1.6 µg/g) along with FT-IR peaks which also confirmed the metal presence. The semen parameters in smokers that were noticed are low sperm count and morphological changes. Meanwhile, in the seminal plasma of smokers, zinc and DNA fragmentation results were positively correlated with sperm morphology (p < 0.001). Repaired DNA bands were noticed in the in vitro study of aqueous T. arjuna bark, in smokers' semen. T. arjuna bark will act as cryo protector as well as great zinc supplementary to maintain sperm motility and morphology in smokers.

Obesity impedes functional improvement in youth with chronic pain: An initial investigation.

BACKGROUND: Youth with chronic pain are at higher risk for obesity than the general population. In youth with chronic pain, obesity exacerbates pain-specific activity limitations, and in adults with chronic pain, obesity perpetuates a cycle of disability. The current study examined whether weight status predicts functional disability outcomes over time in youth with chronic pain. METHODS: Data were obtained from a retrospective chart review of patients who consented to participate in a longitudinal outcomes study. The Child Activity Limitations Questionnaire was used to assess functional disability at intake, 1-, and 3-month follow-up. Height and weight were measured at intake. A linear mixed model was used to test whether weight status and time predicted functional disability. Trend analysis with polynomial contrasts was used to test whether improvements in functional disability showed a linear trend over time. RESULTS: The linear mixed model analysis showed a main effect of weight, suggesting that youth with higher BMI demonstrated less improvement in functional disability over time. The trend analysis suggested that improvements in functional disability were consistent with a linear trend for both healthy weight and overweight participants, but not for obese participants. CONCLUSION: These findings demonstrate that obesity impedes improvement in functioning for youth with chronic pain. Despite multidisciplinary pain treatment, youth with comorbid chronic pain and obesity demonstrate greater functional disability at follow-up and little improvement over time. These results support the need for interventions specifically tailored to the unique challenges faced by youth with comorbid chronic pain and obesity. SIGNIFICANCE: This study shows that obesity impedes improvement in functioning for youth with chronic pain. On the basis of these findings, interventions should be tailored to the unique challenges of this population.

Development of non-invasive method for assessment of hepatic steatosis.

Steatosis is a critical feature of liver disease and is considered to play a pivotal role in the progression of nonalcoholic fatty liver disease, as well as being a surrogate marker of metabolic syndrome. The purpose of this study was to develop a non-invasive diagnostic method for assessment of liver steatosis. It is well known that ultrasonic velocity depends on materials and temperature. For example, the ultrasonic velocity in water is 1530m/s at 37°C and 1534m/s at 39°C, while that in fat is 1412m/s at 37°C and 1402m/s at 39°C. On this basis, we thought that the percentage of fat in hepatic steatosis could be assessed by detecting changes of ultrasonic in the liver, caused by warming. In order to confirm the effectiveness of this method, we obtained the ultrasonic velocity changes of tissue phantom including lard oil and the liver of living rabbit by ultrasonic warming, and then succeeded in 2-D imaging of ultrasonic velocity changes of the phantom and the liver of living rabbit. We named this the ultrasonic velocity-change method. The experimental results show the possibility that hepatic steatosis could be characterized using our novel, non-invasive method.

Regional myocardial perfusion under exchange transfusion with liposomal hemoglobin: in vivo and in vitro studies using rat hearts.

The purpose of this study was to test the hypothesis that exchange transfusion with liposomal hemoglobin (LH) reduces the microheterogeneity of regional myocardial flows while sustaining cardiac function. Neo Red Cell mixed with albumin was used as the LH solution, in which the LH volume fraction was 17 approximately 18% and hemoglobin density was nearly two-thirds smaller than in rat blood. Regional myocardial flows in left ventricular free walls were measured by tracer digitalradiography (100-mum resolution) in anesthetized rats with or without 50% blood-LH exchange transfusion. Within-layer flow distributions showed lower heterogeneity with (n = 8) than without (n = 8) LH transfusion. No extravasation of hemoglobin was confirmed by 3,3-diaminobenzidin staining (n = 2). Carotid flow increased by 68% due to LH transfusion, whereas arterial pressure and heart rate remained unchanged. On the other hand, cross-circulated rat hearts (n = 7) were used to evaluate the effects of 50% blood-LH exchange on coronary flow and tone preservation under 300-beats/min pacing and 100-mmHg perfusion pressure. Blood-LH exchange caused a 71% increase of coronary flow and 10% decrease of percent flow increase during hyperemia after 30-s flow interruption. Myocardial O(2) supply and consumption increased by 9% and 10%, respectively, whereas myocardial O(2) extraction remained unchanged. The large increases of in vivo carotid flow and coronary flow in cross-circulated hearts due to LH coperfusion could be explained by the reduction of apparent flow viscosity. These results suggest that under LH coperfusion, the microheterogeneity of myocardial flows decreases with increased coronary flow while fairly preserving coronary tone and cardiac function.

Anti-Ma2 antibody related paraneoplastic limbic/brain stem encephalitis associated with breast cancer expressing Ma1, Ma2, and Ma3 mRNAs.

A 69 year old woman presented with cognitive impairment and supranuclear gaze palsy caused by paraneoplastic limbic/brain stem encephalitis associated with atypical medullary breast carcinoma. The cerebrospinal fluid from the patient harboured an anti-neuronal cell antibody against Ma2 antigen, but not against Ma1 or Ma3 antigen. Despite the antibody being restricted to the Ma2 antigen, the patient's cancer tissue expressed Ma1, Ma2, and Ma3 mRNAs. These results, and the expression of Ma2 mRNA in an atypical medullar breast carcinoma in another patient without paraneoplastic encephalitis, indicate that the induction of anti-Ma2 antibody depends on host immunoreponsiveness and not on the presence of the antigen itself in the cancer.

Efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI in Japanese patients with moderately persistent asthma.

OBJECTIVE: The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI. METHODOLOGY: Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials. RESULTS: At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated. CONCLUSION: Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.

A double-blind, placebo-controlled steroid-sparing study with budesonide Turbuhaler in Japanese oral steroid-dependent asthma patients. Japanese Pulmicort Turbuhaler study group.

OBJECTIVE: The aim of this study was to evaluate the oral steroid-sparing capacity of budesonide Turbuhaler. METHODOLOGY: One hundred and thirteen oral steroid-dependent patients were treated for 6 months with placebo or budesonide 800 microg or 1600 microg daily. Every second week the oral steroid dose was reduced if asthma control permitted. RESULTS: The reductions in oral steroid doses were 9, 35 and 60% in the placebo and budesonide 800 microg and 1600 microg groups, respectively. Oral steroid treatment could be discontinued in 4% (placebo), 15% (800 microg) and 23% (1600 microg). Mean peak expiratory flow values increased by 21 and 24 L/min in the budesonide groups but decreased by 6 L/min in the placebo group. Asthma attack, activity and sleep scores remained unchanged showing maintained efficacy. Plasma cortisol levels increased and an adrenocorticotropic hormone test showed improved adrenocortical response in both budesonide groups, indicating improved safety. Adverse drug reactions were infrequent and mild in all study groups. CONCLUSION: Budesonide Turbuhaler, 800 microg and 1600 microg daily, resulted in a significant reduction in oral steroid usage in steroid-dependent patients. The effect was achieved with maintained asthma control together with improvements in lung and adrenal functions.

A double-blind, placebo-controlled dose-response study with budesonide Turbuhaler in Japanese asthma patients. Japanese Pulmicort Turbuhaler study group.

OBJECTIVE: The aim of this study was to investigate the dose-response for inhaled budesonide via Turbuhaler in Japanese patients with mild to moderate asthma. METHODOLOGY: Inhaled budesonide 100 microg, 200 microg, 400 microg or placebo was administered twice daily via Turbuhaler for 6 weeks, to 267 adult Japanese patients (mean age 51 years) with mild-to-moderate, non-steroid-dependent bronchial asthma, in a double-blind, placebo-controlled, randomized, parallel group study. The patients had to be symptomatic for more than 3 days/week and have an average morning peak expiratory flow (PEF) 50-80% of predicted normal value. RESULTS: The response to budesonide was rapid, all treatments showing a significant improvement in morning PEF after 1 week (P<0.05). During week 6, mean improvements of 15, 45, 53 and 71 L/min were observed for the placebo, 200 microg, 400 microg and 800 microg budesonide groups, respectively. Compared with placebo all improvements in the budesonide groups were statistically significant and a significant dose-response was demonstrated (P<0.001). The difference between the 200 microg and 800 microg doses was significant. Also, for several secondary efficacy variables (e.g. evening PEF, symptom score, treatment score, daily activity score and sleep score) significant dose-responses were shown. Other variables included the investigators' assessments of improvement and usefulness. They also showed statistically significant dose-response relationships and confirmed the rapid onset of action. Budesonide was well tolerated at all tested doses, with a low incidence of adverse events, all of which were minor in severity. CONCLUSIONS: Budesonide Turbuhaler in the doses 100 microg to 400 microg twice daily was effective, well tolerated and showed a rapid onset of action in patients with mild-to-moderate asthma. Dose-response was demonstrated for several variables of clinical efficacy.

[Hospitalization reduction by an asthma tele-medicine system].

We examined an effectiveness of a new asthma telemedicine system in reducing hospitalizations using a multi-site randomized control study. In this program, a nurse under physician supervision monitors the patient's airway status at home and provides instructions to individuals via the telephone, helping them manage exacerbations as well as reinforcing proper use of a zone-controlled management plan. Patients with a high risk for hospitalization were screened based on the numbers of emergency room visits and hospitalizations found in a previous study and randomly assigned to either the telemedicine or control group. After a six-month study period, an 83% reduction in hospitalization was demonstrated in the telemedicine group versus the control group, with a P value of 0.01. Improvement of peak expiratory flow and symptoms were also shown in the study group. We conclude that the key success factors in home asthma management for poorly controlled asthma patients are early detection of exacerbations through daily peak flow monitoring, compliance with prescribed daily prophylactic anti-inflammatory steroid medications, and immediate action as specified by a zone-controlled action plan upon the first signs of deterioration.

A diffuse alveolar hemorrhage in a human T-lymphotropic virus type I carrier with acute cerebellar ataxia and interstitial pneumonitis: an autopsy case report.

A 76-year-old HTLV-I-positive male with acute cerebellar ataxia was suffering from dyspnea on exertion. Chest CT suggested interstitial pneumonitis. Methylprednisolone pulse therapy improved his symptoms and chest CT findings. Twelve months after discharge, when the prednisolone dose was tapered to 5 mg every other day, his lung lesion recurred. The lesion responded initially to steroid therapy. However, hypoxemia intractable to steroid pulse therapy developed and the patient died of respiratory failure. The autopsy revealed diffuse alveolar hemorrhage with no finding of vasculitis. This is the first case report of diffuse alveolar hemorrhage in an HTLV-I carrier.

Nuclear factor kappa B mediates interleukin-8 production in eosinophils.

BACKGROUND: Recent reports indicate that in response to various stimuli, eosinophils produce a variety of cytokines (e.g. IL-8) which play pivotal roles in allergic inflammation. In that regard, the transcription factor, nuclear factor, Kappa B (NF-kappaB), is an important activator of tumor-necrosis-factor-alpha (TNF-alpha)-induced IL-8 gene expression in monocytes, lymphocytes and neutrophils. We therefore investigated the role played by NF-kappaB in cytokine production induced by stimulation of eosinophils with the proinflammatory cytokines, granulocyte-monocyte colony-stimulating factor (GM-CSF) and TNF-alpha. METHODS: Peripheral blood samples were obtained from human subjects with slight to moderate eosinophilia. NF-kappaB activation elicited by exposing cells to GM-CSF and/or TNF-alpha was investigated using immunohistochemistry and gel shift assays. To functionally assess the effects of NF-kappaB translocation, IL-8 production was also examined using an enzyme-linked immunosorbent assay. RESULTS: Stimulation of eosinophils with GM-CSF + TNF-alpha induced significant increases in the synthesis and secretion of IL-8 which were associated with translocation of NF-kappaB p50 into the nucleus. The binding of NF-kappaB to the DNA was verified by the gel shift assays. IL-8 production was significantly inhibited by N-acetyl-L-cysteine, FK506 and MG-132, inhibitors of NF-kappaB activation and translocation. CONCLUSION: On the basis of our findings, we conclude that activation and translocation of NF-kappaB plays a crucial role in the signal-transduction pathway leading to the synthesis and release of IL-8 by eosinophils.

Diesel exhaust particulate induces airway hyperresponsiveness in a murine model: essential role of GM-CSF.

BACKGROUND: Inhaled pollutants were recently shown to be responsible for an increased incidence of airway allergic diseases, including asthma. A common feature of all forms of asthma is airway hyperresponsiveness. OBJECTIVE: Our purpose was to elucidate the effects of diesel exhaust particulate (DEP), one of the most prevalent inhaled pollutants, on airway responsiveness. METHODS: A/J and C57Bl/6 mice were used; the former are genetically predisposed to be hyperresponsive to acetylcholine, whereas the latter are not. DEP was administered intranasally for 2 weeks, after which pulmonary function was analyzed by whole-body plethysmography. RESULTS: Intranasal administration of DEP increased airway responsiveness to acetylcholine in both A/J and C57Bl/6 mice and induced displacement of ciliated epithelial cells by mucus-secreting Clara cells. The effect was mediated by M(3) muscarinic receptors. Acetylcholine-evoked bronchial constriction was reversed by administration of terbutaline, a beta(2)-adrenergic antagonist, which is also characteristic of human asthma. Intranasal administration of antibody raised against GM-CSF abolished DEP-evoked increases in airway responsiveness and Clara cell hyperplasia. The antibody raised against IL-4 also inhibited DEP-evoked increases in airway responsiveness. However, it was to a lesser extent compared with antibody against GM-CSF. In addition, DEP stimulated GM-CSF messenger RNA expression in the lung. CONCLUSION: DEP induces airway hyperresponsiveness by stimulating GM-CSF synthesis.

[Baroreflex function in patients with Binswanger's encephalopathy].

To analyze the baroreflex function in Binswanger's encephalopathy, we performed head-up tilting (HUT) in three steps (20 degrees, 40 degrees, and 60 degrees for 5 min.) and evaluated changes in blood pressure, heart rate, plasma noradrenaline (NA) and plasma arginine vasopressin (AVP) in 15 patients with Binswanger's encephalopathy (mean age; 70.1 +/- 5.6 years), 10 patients with lacunar infarction (mean age; 72.3 +/- 6.3 years) and eight normal controls (mean age; 69.0 +/- 4.3 years). In the patients with Binswanger's encephalopathy, the resting blood pressure was higher than that in the other two groups and the blood pressure decreased by more than 20 mmHg in five cases and by 15 mmHg in one case after HUT. In all groups, the heart rates and NA increased significantly after HUT, but the AVP levels were not significantly increased after HUT in the patients with Binswanger's encephalopathy. In conclusion, central baroreceptor pathways involved in the function of AVP release, brainstem-hypothalamic pathways are impaired in Binswanger's encephalopathy.

[Vasculo-Behcet's disease with fatal massive hemoptysis].

A 39-year-old man was admitted to our hospital because of hemoptysis. A chest X-ray film on admission showed a patchy shadow in the left lower lung field. Computed tomography revealed nodular opacities in the left pulmonary artery. The patient had history of oral ulcers, erythema nodosum, pustular lesions, and genital ulcers. Furthermore, the needle reaction was positive. Our diagnosis was an incomplete type of Behcet's disease. A radionuclide-venography and lung-perfusion study disclosed deep-vein thrombosis. Combined therapy with prednisolone, colchicine, and indomethacin farnesil was initiated, but the patient died of massive hemoptysis. Pathological examination revealed a ruptured aneurysm in the bronchus segmentalis apacalis and thrombotic angitis in the inferior vena cava. Behcet's disease is rarely a cause of hemoptysis. However, the prevalence of hemoptysis due to pulmonary vasculitis in patients with Behcet's disease has been reported to be 5 to 10% which is not so rare. Because of the poor prognosis, we want to emphasize Behcet's disease as a cause of hemoptysis.

[The significance of hypoplasia of the circle of Willis in patients with Binswanger-type cerebrovascular disease].

We evaluated the correlation between hypoplasia of the circle of Willis detected by MR angiography and ischemia of the white matter in patients with Binswanger-type cerebrovascular disease. We defined P1 hypoplasia as the condition in which the posterior cerebral artery at P1 protein was narrower than the posterior communicating artery, and A1 hypoplasia as that in which the ratio of the one anterior cerebral artery to the other at A1 portion was 1:2 or less. Of 68 patients with this disease. 33 (48.5%) had P1 hypoplasia and 23 (30.9%) had A1 hypoplasia. These incidences were significantly higher than those of patients with lacunar infarction (138 cases), where P1 and A1 hypoplasia were 29.0% and 18.1% respectively. P1 hypoplasia tended to be found more frequently in patients with lacunar infarction having advanced periventricular hyperintensity than in those having mild one. The large intracranial vessels, as seen by MR angiography, were less stenotic, and the serum concentration of apolipoprotein A-I was higher and B/A-I was lower in hypoplasia cases suffering from Binswanger-type cerebrovascular disease than in non-hypoplasia cases. In summary, hypoplasia of the circle of Willis was considered to precipitate the onset or progression of this disease without any relationship to arteriosclerosis.

[The usefulness of carotid artery ultrasonography in patients with Binswanger's encephalopathy].

Carotid artery ultrasonography (B-mode and Duplex method) was conducted in 49 cases of Binswanger's encephalopathy (group B) to compare with 189 cases of lacunar infarction (group L). With B-mode method, there was no significant difference in the amount of plaque between group B and group L, but the inner diameter of the common carotid artery was greater in group B. Using Duplex method, we measured maximum systolic flow velocity (Max), minimum diastolic flow velocity (Min) and time velocity integral (TVI). We found that those data were consistently lower in group B than in group L, with a correlation to the severity of mental impairment. The decrease in Max in group B, which has diffuse arteriosclerosis, indicates a decline in cardiac function, while the decrease in Min indicates an increase of intracranial small vessel resistance. The lower TVI in group B is thought to reflect a loss of velocity in cerebrovascular circulation due to the decrease in Max and Min. Carotid artery ultrasonography thus proved useful in evaluating the pathogenesis and progression of the disease.

[A familial case of postural reflex disorder presenting high intensity area mainly in the globus pallidus on T1-weighted cerebral MRI without clear liver damage].

A 56-year-old woman was admitted because of chronic postural reflex disorder. A cerebral MRI revealed symmetrical high intensity area mainly in the globus pallidus on T1-weighted image. The symptom became manifested as gait disturbance from the age of 2 and gradually progressed. Her condition has, however, remained stable since the age of 26. The only sign of parkinsonism was akinesia. There was clear retropulsion but cerebellar ataxia was minimal, and dystonia was negligible. She had no dementia. Her parents were cousins and similar symptoms and high intensity area were found in one of her sisters. Routine liver function tests were normal, with only ICG elevated. Serum copper and ceruloplasmin were normal. A hereditary factor was suspected. There are no similar cases reported in the literature, thus we thought it worth reporting.

[Clinical significance of orthostatic blood pressure decline in patients with Binswanger-type infarction].

We analysed the blood pressure change in 40 patients with Binswanger-type infarction after 10 minutes of 90 degrees head-up tilting to clarify the clinical significance of orthostatic blood pressure decline observed in this disease. We investigated the correlation of orthostatic decline in systolic blood pressure to dementia, gait disturbance and nocturnal decrease in 24-hour variation of systolic blood pressure. Orthostatic blood pressure decline in patients with this disease was significantly marked in comparison with that in 50 patients with lacunar infarction, especially in the males. This blood pressure decline was significant in patients with dementia and moderate or severe gait disturbance, compared with those without such symptoms. There was no difference in orthostatic change between patients suffering from this disease with non-dementia and mild or absent gait disturbance and those with only lacunar infarction. Orthostatic blood pressure decline was found to be correlated significantly with the disorder of nocturnal blood pressure decrease. It is suggested that the decline of blood pressure on standing is a parameter indicating the progression of this disease.