Monocyte and Basophil Counts as Predictors of Neutrophil Count Recovery in Patients with Thiamazole-Induced Agranulocytosis.

Purpose: Thiamazole (MMI) is frequently used for the treatment of Graves' disease, but it occasionally induces agranulocytosis at the beginning of the treatment. To date, the predictive factors of recovery from MMI-induced agranulocytosis remain unclear. The primary aim of this study was to evaluate the predictive factor of the recovery time from MMI-induced agranulocytosis. Method: This was a retrospective cohort study performed in a university hospital and a thyroid hospital. We included 27 Japanese patients with Graves' disease with MMI-induced agranulocytosis diagnosed during follow-up. All patients were administrated recombinant human granulocyte colony-stimulating factor daily until they had a neutrophil count>1 000/µL, which was defined as recovery. The predictive factors associated with recovery time were estimated using multivariable regression analysis. Results: At the onset of agranulocytosis, the median administration period of MMI was 33 days, the average white blood cell count was 1 896/µL, and the median neutrophil count was 22/µL. The median recovery time was 4 days. Stepwise multivariate regression analysis identified the monocyte and basophil counts to be significant predictors of MMI-induced agranulocytosis. Conclusion: Patients with agranulocytosis and decreased monocyte and basophil counts at onset may recover late and require careful treatment.

Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts with HLA-A24-restricted ovarian cancer-specific CTLs.

Here, we describe an human leukocyte antigen (HLA)-A*24:02-restricted cytotoxic T-lymphocyte (CTL) clone, 1G3, established from naïve CD8(+) T-lymphocytes obtained from a healthy donor stimulated with HLA-modified TOV21G, an ovarian cancer cell line. The 1G3 clone responds not only to ovarian cancer cells in the context of HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive T-cell receptor recognition. Expression screening using a complementary DNA library constructed from TOV21G messenger RNA revealed that this alloreactivity was mediated through the nine-mer peptide VRTPYTMSY, derived from RNA-binding motif protein 4. To our knowledge, this study presents the first example of the allorecognition of an HLA-Cw molecule by HLA-A-restricted T-cells, thereby revealing a naturally processed epitope peptide. These findings provide the structural bases for the allorecognition of human T-cells. In addition, this study suggests that unexpected alloresponses occur in certain HLA combinations, and further study is needed to understand the mechanisms of alloreactivity for better prediction of alloresponses in clinical settings.

Constipation is not associated with colonic diverticula: a multicenter study in Japan.

BACKGROUND: The association of diverticula with bowel habits is unclear. We therefore analyzed the association between diverticula and bowel habits in over 1000 Japanese individuals. METHODS: Japanese subjects who underwent total colonoscopies at seven centers in Japan from June to September 2013 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale, and stool form was assessed using a part of the Bristol Scale and Rome ΙΙΙ criteria. Diverticula were diagnosed by colonoscopy with a transparent soft-short hood. KEY RESULTS: The study evaluated 1066 subjects, 648 males and 418 females (ratio, 1.55 : 1), of mean age 63.9 ± 13.0 years. After adjusting for age and sex, the presence of constipation was associated with a significantly reduced likelihood of diverticula (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52-0.93). When assessed according to the location of diverticula, the presence of constipation was associated with a significantly decreased likelihood of left-sided (OR = 0.39, 95% CI 0.16-0.93), but not right-sided (OR = 1.10, 95% CI 0.48-2.53), diverticula. Furthermore, stool form was unrelated with the presence or absence of diverticula. CONCLUSIONS & INFERENCES: The wide-spread hypothesis that constipation was associated with colonic diverticula was not supported. Rather, we found that the absence of diverticula was associated with constipation, suggesting the need to reassess the etiology of colonic diverticula.

Influence of sumatriptan on gastric accommodation and on antral contraction in healthy subjects assessed by ultrasonography.

BACKGROUND: Oral sumatriptan administration has been reported to delay gastric emptying after liquid meals. The aim of this study was to determine whether delayed gastric emptying is caused by enhanced gastric accommodation, impaired antral contractions, or both using ultrasonography. METHODS: Ten healthy volunteers were enrolled in this randomized two-way crossover study. After overnight fasting, the subjects received the liquid meal 60 min after ingesting a 50 mg sumatriptan tablet with 50 mL of water or 50 mL of water alone (control). The cross-sectional area of the proximal stomach was measured in a supine position after every 100 mL. The frequency and amplitude of the antral contractions were measured in a slightly backward sitting position. The intragastric distribution of the liquid meal was assessed by calculating the proximal stomach/distal stomach ratio (prox/distal ratio). KEY RESULTS: The cross-sectional area after drinking 100, 200, and 300 mL of the liquid meal (oral sumatriptan vs control) was 34.49 vs 15.11 cm(2) (P = 0.0051), 48.00 vs 30.61 cm(2) (P = 0.0166), and 58.67 vs 47.19 cm(2) (P = 0.0125), respectively. There was no significant difference in the amplitude of contractions, contraction cycle, motility index, and prox/distal ratio (97.15 vs 97.93%, P = 0.0745; 19.42 vs 19.5 s, P= 0.8590; and 887.58 vs 889.22, P = 0.5751; 9.75 vs 8.41, P = 0.8785; respectively). CONCLUSIONS & INFERENCES: Oral sumatriptan administration enhanced gastric accommodation after the ingestion of liquid nutrients, but had no significant effect on antral contractions or intragastric distribution in healthy subjects.

Clinical associations and risk factors for bleeding from colonic angiectasia: a case-controlled study.

AIM: A case-controlled study was performed to investigate the association of colonic angiectasia with other conditions and to identify risk factors for bleeding. METHOD: Information was collected from all patients who underwent colonoscopy at our hospital between January 2008 and December 2010. Data on 90 individuals with angiectasia [58 men; median age 69 (26-92) years] were compared with those of 180 individuals without angiectasia, matched for gender and age. RESULTS: Multivariate analysis showed that occult gastrointestinal bleeding [odds ratio (OR) 2.523; 95% confidence interval (CI) 1.238-5.142], liver cirrhosis (OR 13.195; 95% CI 3.502-49.711), chronic renal failure (OR 6.796; 95% CI 1.598-28.904) and valvular heart disease (OR 6.425; 95% CI 1.028-40.165) were identified as significant predictors of the presence of colonic angiectasia. Eight patients were diagnosed with bleeding from angiectasia. Cardiovascular disease (OR 22.047; 95% CI 1.063-457.345) and multiple angiectasias (P-value 0.0019) were identified as significant risk factors for active bleeding. Medication and a large size were not associated with an increased risk of bleeding. CONCLUSION: The presence of colonic angiectasia was associated with valvular heart disease, liver cirrhosis and chronic renal failure. Valvular heart disease and multiple lesions increased the risk of bleeding.

Body cavity fluid can induce epithelial and mesothelial differentiation from CD34 positive peripheral blood stem cells in vitro.

OBJECTIVE: Primary culture of CD34 positive stem cells collected from human peripheral blood was performed with and without supplementation with concentrated ascitic fluid; morphological and immunocytochemical pictures of cultured cells were taken chronologically and compared. METHODS: CD34-positive stem cells collected from peripheral blood were cultured for 1, 24 and 48 hours. Concentrated ascitic fluid was added to the plates for the 24-and 48-hour cultures. For immunocytochemical studies, CD34, AE1/AE3, Ber-Ep4 (EA), EMA, EGFR, CD31, CA125 and D2-40 monoclonal antibodies were used. RESULTS: After culture, small round cells with naked nuclei began to enlarge and to exhibit various changes in the cytoplasm and nucleus. Supplementation with concentrated body cavity fluid enhanced these changes. CD34-positive cells with small round cell features were detected 1 hour after culture and these had no epithelial or mesothelial markers. After 24 hours, CD34-positive cells had disappeared and cells weakly positive for EGFR, EMA, CA125 and D2-40 were detected. Cells with strong and moderate positive reactions for EGFR, AE1/AE3, EA, EMA, D2-40 and CA125 were detected after 48 hours. Supplementation with concentrated body cavity fluid increased the intensity and number of positive cells for these markers compared with the control group. The positive reaction, not only for the epithelial markers such as EGFR and AE1/AE3, but also for mesothelial markers such as CA125 and D2-40, was found to be increased in small numbers of cells in direct proportion to the duration of the primary culture of the peripheral blood cells. CD31, characteristically expressed in endothelial cells, was negative in the cultured cells. CONCLUSION: Supplementation of peripheral blood CD34-positive stem cells with body cavity fluid in vitro enhanced their differentiation toward cells of an epithelial or mesothelial phenotype, concomitant with loss of immunoreactivity for CD34. It is assumed that the routine cytological observation of cells obtained from body cavity fluid might cause possible cytomorphological and immunophenotypical changes due to the action of the growth factors contained in the body cavity fluid.

Cold stress changes the concanavalin A-positive glycosylation pattern of proteins expressed in the basal parts of rice leaf sheaths.

Post-translational modifications such as glycosylation are important for changing the properties and functions of proteins. To analyze the importance of glycosylation during cold stress in rice, a proteomics approach was used. Proteins extracted from the basal part of rice leaf sheaths were separated by two-dimensional polyacrylamide gel electrophoresis, and subjected to lectin blot analysis using concanavalin A. From a total of 250 detected proteins, 22 reacted with the lectin, suggesting that they were N-glycosylated proteins. To determine how N-glycosylation of these proteins is affected by cold stress, rice seedlings were incubated at 5 degrees C for 48 h, and proteins extracted from the basal parts of leaf sheaths were analyzed by the lectin blot assay. Cold stress changed the reactivity toward the lectin for 12 of the 22 glycoproteins. The identity of the 12 proteins was determined by protein sequencing and mass spectrometry with the majority of these glycoproteins being categorized as involved in energy production. Furthermore, calreticulin, one of the 12 glycoproteins, was also phosphorylated as a result of cold stress. These results indicate that cold stress of the basal parts of rice leaf sheaths changes the glycosylation and phosphorylation profiles of calreticulin, a key protein that regulates the quality control of other proteins.

[Investigation of the local heating caused by a closed conducting loop at clinical MR imaging: Phantom study].

PURPOSE: Several reports have suggested that unusual thermal injuries in magnetic resonance (MR) imaging have occurred due to a closed conducting loop formed accidentally in a part of the patient's body. In this study, we investigated the relationship between the increases in temperature and several parameter settings for MR imaging by use of a human body-equivalent phantom. METHOD AND MATERIALS: A standard clinical 1.5T MR system (SIGNA HORIZON; GE) and a pelvic phased-array coil were used. The human body-equivalent phantom (agar, 0.9% saline, antiseptic) simulated a part of the pelvis and both femurs in a patient. A closed conducting loop could be reproduced when two ends of femurs contacted each other at a point, so that we could measure the temperature changes without and with a closed conducting loop. The temperature of the phantom was measured at the contact point of a closed conducting loop and the center of phantom by use of an optical fiber thermometer which was immune to the influences of radiofrequency (RF) and magnetic and electronic fields. We tested two imaging sequences of spin echo (SE) and fast spin echo (FSE) with 60 minutes of scanning time. In addition to the standard imaging sequences we measured temperature changes without the RF irradiation or gradient magnetic fields. The average temperature changes were recorded from five measurements which were repeated at intervals of more than one day. RESULTS: When the closed conducting loop was reproduced, the temperatures at the contact point significantly increased (p<0.001) compared with the temperatures at the center of phantom. The temperature changes at 60 minutes of scanning time were 7.0 and 8.1 degrees C by use of the SE and FSE, respectively. There were no significant temperature changes when the imaging was performed without the RF irradiation. CONCLUSION: Our result obtained by use of a human body-equivalent phantom demonstrated that local heating, which can lead to thermal injuries accidentally, could occur when a closed conducting loop was formed in part of the patient body. CLINICAL RELEVANCE/APPLICATION: Radiologists should be more careful about local heating which can occur in patients during clinical MR imaging by a closed conducting loop.

Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathy.

BACKGROUND: Neuronal intranuclear hyaline inclusion disease (NIHID), a rare neurodegenerative disease in which eosinophilic intranuclear inclusions develop mainly in neurons, has not yet been described to present as hereditary motor-sensory and autonomic neuropathy. METHODS: Patients in two NIHID families showing peripheral neuropathy were evaluated clinically, electrophysiologically, and histopathologically. RESULTS: In both families, patients had severe muscle atrophy and weakness in limbs, limb girdle, and face; sensory impairment in the distal limbs; dysphagia, episodic intestinal pseudoobstruction with vomiting attacks; and urinary and fecal incontinence. No patients developed symptoms suggesting CNS involvement. Electrophysiologic study showed the reduced motor and sensory nerve conduction velocities and amplitudes, and also extensive denervation potentials. In sural nerve specimens, numbers of myelinated and unmyelinated fibers were decreased. In two autopsy cases, eosinophilic intranuclear inclusions were widespread, particularly in sympathetic and myenteric ganglion neurons, dorsal root ganglion neurons, and spinal motor neurons. These neurons also were decreased in number. CONCLUSION: Patients with neuronal intranuclear hyaline inclusion disease (NIHID) can manifest symptoms limited to those of peripheral neuropathy. NIHID therefore is part of the differential diagnosis of hereditary motor-sensory neuropathy associated with autonomic symptoms. Intranuclear hyaline inclusions in Schwann cells and in the myenteric plexus may permit antemortem diagnosis of NIHID.

Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat.

AIMS/HYPOTHESIS: The spontaneously diabetic Torii (SDT) rat has recently been established as a model of type 2 human diabetes mellitus. Male SDT rats develop severe diabetic ocular complications. This study investigated the nature of the ocular complications in this model and addressed the question of whether the SDT rat is a good model of human proliferative diabetic retinopathy. METHODS: Male SDT rats aged 50 weeks were studied for a period of 8 months. Under deep anaesthesia, one eye of each animal was enucleated following perfusion with fluorescein dextran and a retinal flat mount was prepared to study vascular structure. The other eye was enucleated and investigated histologically by haematoxylin-eosin and azan staining and by immunohistochemistry using antibodies against vascular endothelium (Griffonia simplicifolia isolectin B4 antibody) and vascular endothelial growth factor (VEGF). RESULTS: From the vascular structure study, 17 of 32 rats (53%) showed proliferative retinopathy without vascular non-perfusion. The histological study revealed traction retinal folds in rats with proliferative retinopathy. Azan staining showed some proliferative matrix in rats with normal retinal structure and those with proliferative retinopathy compared with normoglycaemic controls. Staining with Griffonia simplicifolia isolectin B4 antibody showed no specific vascular changes in any of the rats, while VEGF staining revealed higher immunoreactivity in the retina of rats with normal retinal structure and those with proliferative retinopathy, but only low immunoreactivity in the control animals. CONCLUSIONS/INTERPRETATION: There appear to be differences between the SDT rat model of diabetic retinopathy and human proliferative diabetic retinopathy, as the SDT rat develops retinal neovascularisation without retinal ischaemia. This very unique display of ocular neovascularisation may be caused by increased expression of VEGF.

Density, proportion, and dendritic coverage of retinal ganglion cells of the common marmoset (Callithrix jacchus jacchus).

We performed a quantitative analysis of M and P cell mosaics of the common-marmoset retina. Ganglion cells were labeled retrogradely from optic nerve deposits of Biocytin. The labeling was visualized using horseradish peroxidase (HRP) histochemistry and 3-3'diaminobenzidine as chromogen. M and P cells were morphologically similar to those found in Old- and New-World primates. Measurements were performed on well-stained cells from 4 retinas of different animals. We analyzed separate mosaics for inner and outer M and P cells at increasing distances from the fovea (2.5-9 mm of eccentricity) to estimate cell density, proportion, and dendritic coverage. M cell density decreased towards the retinal periphery in all quadrants. M cell density was higher in the nasal quadrant than in other retinal regions at similar eccentricities, reaching about 740 cells/mm(2) at 2.5 mm of temporal eccentricity, and representing 8-14% of all ganglion cells. P cell density increased from peripheral to more central regions, reaching about 5540 cells/mm(2) at 2.5 mm of temporal eccentricity. P cells represented a smaller proportion of all ganglion cells in the nasal quadrant than in other quadrants, and their numbers increased towards central retinal regions. The M cell coverage factor ranged from 5 to 12 and the P cell coverage factor ranged from 1 to 3 in the nasal quadrant and from 5 to 12 in the other quadrants. These results show that central and peripheral retinal regions differ in terms of cell class proportions and dendritic coverage, and their properties do not result from simply scaling down cell density. Therefore, differences in functional properties between central and peripheral vision should take these distinct regional retinal characteristics into account.

Density, proportion, and dendritic coverage of retinal ganglion cells of the common marmoset (Callithrix jacchus jacchus)

We performed a quantitative analysis of M and P cell mosaics of the common-marmoset retina. Ganglion cells were labeled retrogradely from optic nerve deposits of Biocytin. The labeling was visualized using horseradish peroxidase (HRP) histochemistry and 3-3'diaminobenzidine as chromogen. M and P cells were morphologically similar to those found in Old- and New-World primates. Measurements were performed on well-stained cells from 4 retinas of different animals. We analyzed separate mosaics for inner and outer M and P cells at increasing distances from the fovea (2.5-9 mm of eccentricity) to estimate cell density, proportion, and dendritic coverage. M cell density decreased towards the retinal periphery in all quadrants. M cell density was higher in the nasal quadrant than in other retinal regions at similar eccentricities, reaching about 740 cells/mm² at 2.5 mm of temporal eccentricity, and representing 8-14 percent of all ganglion cells. P cell density increased from peripheral to more central regions, reaching about 5540 cells/mm² at 2.5 mm of temporal eccentricity. P cells represented a smaller proportion of all ganglion cells in the nasal quadrant than in other quadrants, and their numbers increased towards central retinal regions. The M cell coverage factor ranged from 5 to 12 and the P cell coverage factor ranged from 1 to 3 in the nasal quadrant and from 5 to 12 in the other quadrants. These results show that central and peripheral retinal regions differ in terms of cell class proportions and dendritic coverage, and their properties do not result from simply scaling down cell density. Therefore, differences in functional properties between central and peripheral vision should take these distinct regional retinal characteristics into account.

Genotoxic effects of rotenone on cultured lymphocytes

Rotenone is a heterocyclic compound widely used as an insecticide, acaricide and piscicide. Its toxicity is mainly caused by the inhibition of mitochondrial respiratory processes and ATP production, resulting in the generation of reactive oxygen species. Reactive oxygen species can interact with DNA, RNA and proteins, leading to cell damage, followed by death. We used the Comet assay, and we analyzed chromosome aberrations, in order to evaluate the genotoxic and clastogenic effects of rotenone on the different phases of the cell cycle. Cultured human lymphocytes were treated with 1.0, 1.5 and 2.0 microg/mL rotenone during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle. Rotenone induced DNA damage and was clastogenic, but the clastogenicity was detected only with treatments conducted during the G1/S and S phases of the cell cycle. Rotenone also induced endoreduplication and polyploidy in treatments made during G1, while it significantly reduced the mitotic index in all phases of the cell cycle.

Prevalence of rhinitis and related-symptoms in schoolchildren from different cities in Brazil.

By using the standard written questionnaire (WQ), designed for the International Study of Asthma and Allergies in Childhood (ISAAC) we determined the prevalence of rhinitis and its related-symptoms, in Brazilian children and adolescents, living in different cities of the country. The WQ was answered by the parents of 11,403 children aged 6-7 years from five Brazilian cities: Porto Alegre (South, N = 2,846), São Paulo (Southeast, N = 3,005) Uberlândia (Southeast, N = 2,991), Itabira (Southeast, N = 1,151) and Recife (Northeast, N = 1,410). The WQ was also applied to 20,587 adolescents (13-14 years old) living in: Porto Alegre (South, N = 3,195), Curitiba (South, N = 3,004), São Paulo (Southeast, N = 3,008), Uberlândia (Southeast, N = 2,998), Itabira (Southeast, N = 2,134), Salvador (Northeast, N = 3,162) and Recife (Northeast, N = 3,086). The mean response rates were 75% and 95%, for the 6-7 year-old children and for the adolescents, respectively. The data was transcribed to a database (Epi-Info) and analyzed regarding the answers to questions of rhinitis module. The mean prevalence of rhinitis (affirmative response to question 2) was 26.6% and 34.2% in the groups of 6-7 and 13-14 year-old, respectively. Applying the criteria that evaluate the association between nasal and ocular symptoms (affirmative response to question 3) the mean prevalence of allergic rhinitis were 12.8% for the 6-7 year-old children and 18.0% for the adolescents. In conclusion, the prevalence of rhinitis and its related symptoms among children and adolescents living in different Brazilian cities was as high as the prevalence observed in other areas of the world.

Prevalence of rhinitis and related-symptoms in schoolchildren from different cities in Brazil

By using the standard written questionnaire (WQ), designed for the International Study of Asthma and Allergies in Childhood (ISAAC) we determined the prevalence of rhinitis and its related-symptoms, in Brazilian children and adolescents, living in different cities of the country. The WQ was answered by the parents of 11,403 children aged 6-7 years from five Brazilian cities: Porto Alegre (South, N = 2,846), São Paulo (Southeast, N = 3,005) Uberlândia (Southeast, N = 2,991), Itabira (Southeast, N = 1,151) and Recife (Northeast, N = 1,410). The WQ was also applied to 20,587 adolescents (13-14 years old) living in: Porto Alegre (South, N = 3,195), Curitiba (South, N = 3,004), São Paulo (Southeast, N = 3,008), Uberlândia (Southeast, N = 2,998), Itabira (Southeast, N = 2,134), Salvador (Northeast, N = 3,162) and Recife (Northeast, N = 3,086). The mean response rates were 75 % and 95 %, for the 6-7 year-old children and for the adolescents, respectively. The data was transcribed to a database (Epi-Info) and analyzed regarding the answers to questions of rhinitis module. The mean prevalence of rhinitis (affirmative response to question 2) was 26.6 % and 34.2 % in the groups of 6-7 and 13-14 year-old, respectively. Applying the criteria that evaluate the association between nasal and ocular symptoms (affirmative response to question 3) the mean prevalence of allergic rhinitis were 12.8 % for the 6-7 year-old children and 18.0 % for the adolescents. In conclusion, the prevalence of rhinitis and its related symptoms among children and adolescents living in different Brazilian cities was as high as the prevalence observed in other areas of the world (AU)

La prevalencia de rinitis y de sus síntomas en niños y adolescentes brasileños, que viven en diferentes ciudades, fue determinada por el cuestionario escrito (CE), desarrollado por el International Study of Asthma and Allergies in Children (ISAAC). El CE fue respondido por los padres de 11.403 niños con edad entre los 6-7 años, en cinco ciudades brasileñas: Porto Alegre (Sur, N = 2.846), São Paulo (Sudeste, N = 3.005), Uberlândia (Sudeste, N = 2991), Itabira (Sudeste, N = 1.151) e Recife (Nordeste, N = 1.410).En la faja de edad de 13-14 años el CE fue respondido por 20.587 adolescentes que vivían en: Porto Alegre (Sur, N = 3.195), Curitiba (Sur, N = 3.004), São Paulo (Sudeste, N = 3.008), Uberlândia (Sudeste, N = 2.998), Itabira (Sudeste, N = 2.134), Salvador (Nordeste, N = 3.162) e Recife (Nordeste, N = 3.086).La tasa media de respuestas fue un 75 por ciento para los niños menores y un 95 por ciento para los adolescentes. Los datos fueron transcriptos a una base de datos (Epi-info) y el análisis estadístico fue sobre el modulo rinitis del CE ISAAC. La prevalencia media de rinitis (sí a la pregunta 2) fue 26,6 por ciento y 34,2 por ciento en los grupos de 6-7 y 13-14 años respectivamente. Utilizándose el criterio que evalúa la asociación entre síntomas nasales y oculares (sí a la cuestión 3), la prevalencia media de rinitis alérgica fue de un 12,8 por ciento para los niños de 6-7 años y de un 18,0 por ciento para los adolescentes. En conclusión, la prevalencia de rinitis y síntomas relacionados en niños y adolescentes que viven en diferentes ciudades brasileñas fue tan elevada como la que se ha observado en otras partes del mundo (AU)

A controlled trial of an environmental tobacco smoke reduction intervention in low-income children with asthma.

STUDY OBJECTIVES: To determine the effectiveness of a cotinine-feedback, behaviorally based education intervention in reducing environmental tobacco smoke (ETS) exposure and health-care utilization of children with asthma. DESIGN: Randomized controlled trial of educational intervention vs usual care. SETTING: The pediatric pulmonary service of a regional pediatric hospital. PARTICIPANTS: ETS-exposed, Medicaid/Medi-Cal-eligible, predominantly minority children who were 3 to 12 years old and who were seen for asthma in the hospital's emergency, inpatient, and outpatient services departments (n = 87). INTERVENTION: Three nurse-led sessions employing behavior-changing strategies and basic asthma education and that incorporated repeated feedback on the child's urinary cotinine level. MEASUREMENTS: The primary measurements were the urinary cotinine/creatinine ratio (CCR) and the number of acute asthma medical visits. The secondary measurements were number of hospitalizations, smoking restrictions in home, amount smoked, reported exposures of children, and asthma control. RESULTS: The intervention was associated with a significantly lower odds ratio (OR) for more than one acute asthma medical visit in the follow-up year, after adjusting for baseline visits (total visits, 87; OR, 0.32; p = 0.03), and a comparably sized but nonsignificant OR for one or more hospitalization (OR, 0.34; p = 0.14). The follow-up CCR measurement and the determination of whether smoking was prohibited inside the home strongly favored the intervention group (n = 51) (mean difference in CCR adjusted for baseline, -0.38; p = 0.26; n = 51) (60; OR [for proportion of subjects prohibiting smoking], 0.24; p = 0.11; n = 60). CONCLUSIONS: This intervention significantly reduced asthma health-care utilization in ETS-exposed, low-income, minority children. Effects sizes for urine cotinine and proportion prohibiting smoking were moderate to large but not statistically significant, possibly the result of reduced precision due to the loss of patients to active follow-up. Improving ETS reduction interventions and understanding their mechanism of action on asthma outcomes requires further controlled trials that measure ETS exposure and behavioral and disease outcomes concurrently.

Synthesis of a nitrogen analogue of salacinol and its alpha-glucosidase inhibitory activity.

A nitrogen analogue 4 of the naturally occurring sulfonium ion salacinol (1), a potent alpha-glucosidase inhibitor isolated from the Ayruvedic medicine Salacia reticulata, was synthesized and its inhibitory activity against alpha-glucosidase tested. Substitution of the sulfur atom in 1 with a nitrogen reduced the activity considerably. The solid-state stereostructure of the related compound (5) was determined on the basis of single crystal X-ray measurement.

International Study of Asthma and Allergies in Childhood (ISAAC): prevalence of asthma and asthma-related symptoms among Brazilian schoolchildren.

We have studied the prevalence of asthma and its symptoms using a standard written questionnaire (WQ) designed for the International Study of Asthma and Allergies in Children (ISAAC). The WQ (questions 1 through 8 related to asthma) was applied to 13,604 children aged 6-7 years from six Brazilian cities: Porto Alegre (South, N = 2,976), Curitiba (South, N = 1,664), São Paulo (Southeast, N = 3,005), Uberlândia (Southeast, N = 3,002), Itabira (Southeast, N = 1,551) and Recife (Northeast, N = 1,406). At the age of 13-14 years the WQ was applied to 20,554 schoolchildren living in Porto Alegre (South, N = 3,198), Curitiba (South, N = 3,008), São Paulo (Southeast, N = 3,008), Uberlândia (Southeast, N = 3,001), Itabira (Southeast, N = 2,134), Salvador (Northeast, N = 3,119) and Recife (Northeast, N = 3,086). The parents of the younger children answered the WQ, whereas the adolescents answered the questionnaire themselves. The response rates were 72% and 93% for the 6-7-year-old children and for the 13-14-year-old children, respectively. There was a slight predominance of male children in the population studied. In the group of 6-7-year-olds, the prevalence of physician diagnosed asthma was 7.3% for boys and 4.9% for girls: in the group of 13-14-year-olds the rates were 9.8% and 10.2%, respectively. Asthma severity was similar for both age groups, and wheezing following exercise was more frequent among the adolescents. In keeping with studies from other parts of the world, comparison between reported symptoms and diagnosed asthma revealed a significantly lower frequency of diagnosed asthma, suggesting that in the study population, asthma is underdiagnosed.

Fibroblast growth factor-2 decreases hyperoxia-induced photoreceptor cell death in mice.

Fibroblast growth factor-2 (FGF2) has neurotrophic effects in vitro and in vivo. It has been demonstrated to decrease photoreceptor cell death in rats exposed to constant light and in rats with an inherited defect in retinal pigmented epithelium (RPE) phagocytosis, but the effects of intravitreous injections of FGF2 in mice are equivocal. In this study, we used transgenic mice with increased expression of FGF2 in photoreceptors (rhodopsin promoter/FGF2 transgenics) to investigate the effects of sustained increased expression of FGF2 in mice with various types of photoreceptor degeneration, including rd mice that are homozygous for mutated phosphodiesterase beta subunit, Q344ter mice that undergo photoreceptor degeneration because of expression of mutated rhodopsin, and mice exposed to 75% oxygen for 1 or 2 weeks. At P21, the outer nuclear layer was markedly reduced in rd mice or Q344ter mice regardless of whether they inherited the rhodopsin promoter/FGF2 transgene. However, after 2 weeks of exposure to 75% oxygen, outer nuclear layer thickness was significantly reduced in littermate control mice compared to FGF2 transgenic mice (P = 0.0001). These data indicate that increased expression of FGF2 in photoreceptors protects them from hyperoxia-induced damage, but does not decrease cell death related to expression of mutated proteins involved in the phototransduction pathway. This suggests that FGF2 protects photoreceptors from oxidative damage, which may play a role in complex genetic diseases such as age-related macular degeneration.