[Clinico-diagnostic problems in heteroplastic dysembryomas of the mediastinum (HDM)].
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Through inhibition of purine de novo synthesis and enhancement of 6-mercaptopurine (6MP) bioavailability high-dose methotrexate (HDM) may increase the incorporation into DNA of 6-thioguanine nucleotides (6TGN), the cytoxic metabolites of 6MP. Thus, coadministration of 6MP could increase myelotoxicity following HDM. Twenty-one children with standard risk (SR) and 25 with intermediate risk (IR) acute lymphoblastic leukemia (ALL) were studied. During consolidation therapy they received either three courses of HDM at 2 week intervals without concurrent oral 6MP (SR-ALL) or four courses of HDM given at 2 week intervals with 25 mg/m2 of oral 6MP daily (IR-ALL). During the first year of maintenance with oral 6MP (75 mg/m2/day) and oral MTX (20 mg/m2/week) they all received five courses of HDM at 8 week intervals. In all cases, HDM consisted of 5,000 mg of MTX/m2 given over 24 h with intraspinal MTX and leucovorin rescue. Erythrocyte levels of 6TGN (E-6TGN) and methotrexate (E-MTX) were, on average, measured every second week during maintenance therapy. When SR consolidation (6MP: 0 mg), IR consolidation (6MP: 25 mg/m2), and SR/IR maintenance therapy (6MP: 75 mg/m2) were compared, white cell and absolute neutrophil count (ANC) nadir, lymphocyte count nadir, thrombocyte count nadir, and hemoglobin nadir after HDM decreased significantly with increasing doses of oral 6MP. Three percent of the HDM courses given without oral 6MP (SR consolidation) were followed by an ANC nadir <0.5 x 10(9)/l compared to 50% of the HDM courses given during SR/IR maintenance therapy. Similarly, only 13% of the HDM courses given as SR-ALL consolidation induced a thrombocyte count nadir <100 x 10(9)/l compared to 58% of the HDM courses given during maintenance therapy. The best-fit model to predict the ANC nadir following HDM during maintenance therapy included the dose of 6MP prior to HDM (beta = -0.017, P= 0.001), the average ANC level during maintenance therapy (beta = 0.82, P = 0.004), and E-6TGN (beta = -0.0029, P= 0.02). The best-fit model to predict the thrombocyte nadir following HDM during maintenance therapy included only mPLATE (beta = 0.0057, P = 0.046). In conclusion, the study indicates that reductions of the dose of concurrently given oral 6MP could be one way of reducing the risk of significant myelotoxicity following HDM during maintenance therapy of childhood ALL.
OBJECTIVES: The hemodynamic response to ss-blockers alone or with nitrates is highly predictive of efficacy in prevention of variceal bleeding. Hemodynamic monitoring (HDM) requires catheterization of the hepatic vein and measurement of the hepatic venous pressure gradient, the difference between wedged and free hepatic venous pressure. The aim of this study was to compare HDM with no HDM in patients considered for primary pharmacoprophylaxis of esophageal variceal bleeding. METHODS: A decision model was constructed to compare HDM with no HDM in cirrhotic patients with moderate to large esophageal varices. Patients intolerant to beta-blocker therapy would undergo endoscopic variceal ligation; those with an inadequate hemodynamic response (HDR) to beta-blocker therapy could have nitrates added before ligation was considered. Variceal bleeding was treated with ligation, with transjugular intrahepatic portosystemic shunt (TIPS) reserved for refractory bleeding. Probabilities of treatment responses as well as risks of bleeding and mortality were based on published literature. Only direct costs were considered during the 5-yr time horizon. Outcomes were cost in United States dollars, survival length in life-years, and proportions of patients who experienced variceal bleeding, TIPS insertion, and mortality from any cause. RESULTS: In the base case analysis, HDM was either cost-saving ($2,523 US dollars /life-year gained) or cost-effective (incremental cost-effectiveness ratio of $5,200 US dollars/life-year saved) compared with no HDM, depending on whether nitrates were added to beta-blocker therapy. HDM reduced variceal bleeding by nearly 60% and had a small effect on all-cause mortality. In the sensitivity analysis, HDM was sensitive to the time horizon, as it was not cost-effective for a time horizon of <22 months and was not cost-saving before 49 months. The cost-effectiveness of HDM was not sensitive to reasonable variation in the probability of HDR to beta-blocker therapy, risk of bleeding, risk reduction with pharmacotherapy, or to the costs of HDM, bleeding, ligation, or TIPS. Probabilistic sensitivity analysis indicated that HDM was more effective and less costly 100% and 57% of the time, respectively. CONCLUSIONS: Compared with the current standard of no HDM, measuring the hemodynamic response of primary pharmacoprophylaxis substantially reduces the number of bleeding episodes and is cost-effective or cost-saving over a wide range of sensitivity analyses. A randomized trial of HDM is needed to verify its efficacy in clinical practice.
OBJECTIVES: House dust mite (HDM) is a representative inhalant allergen that triggers allergic disease in childhood. The aim of this study is early detection of HDM-specific IgE antibody and prediction of the risk of a positive reaction to this antibody by in vitro parameters in infants with allergic manifestations. STUDY DESIGN: Levels of HDM IgE in a range below the standard cutoff point of 0.35 U/ml, serum concentrations of IgE, and specific IgE antibodies against egg white, cow milk, and soybeans were determined in 108 infants with allergic manifestations at 6 months of age, and these infants were monitored for conversion of HDM IgE to positive levels greater than 0.35 U/ml up to 5 years of age. The presence of active allergic disease at 5 years of age in relation to HDM-specific IgE was also examined. RESULTS: We were able to determine reliably the HDM IgE values between 0.23 and 0.35 U/ml, using a fluorescent enzyme immunoassay that measured the intensity of fluorescence. The HDM IgE levels increased, resulting in positive values, in 54 of 108 subjects during the first 5 years of life. In multiple regression analysis, an HDM IgE value between 0.23 and 0.35 U/ml, a high serum IgE level, and a positive reaction to specific IgE antibody against egg white in infants at 6 months of age proved to be significant predictors of the future positive reaction to HDM IgE (p = 0.0006, 0.0043, and 0.0001). In particular, the sensitivity and specificity of specific IgE antibody against egg white for the conversion of HDM IgE to positive values were the best among these indicators. Moreover, active allergic diseases were observed significantly more often in children with positive HDM IgE values than in children with negative HDM IgE values at 5 years of age (p < 0.001 for each). CONCLUSIONS: A determination of these predictors in infants at 6 months of age can be used for early detection of HDM IgE and would be valuable in a screening test for later allergic disease among infants with allergic manifestations.
BACKGROUND: House dust mites (HDM) are sensitive to humidity. Few studies have adequately examined the potential of dehumidification in reducing HDM numbers. OBJECTIVE: The study examined the effect of portable domestic dehumidifiers, and a behavioural programme to reduce humidity, on HDM counts and HDM allergen levels. METHODS: A randomized controlled trial was undertaken. A total of 76 homes were allocated to three groups that received a portable domestic dehumidifier, a behavioural programme, or no intervention. Humidity, temperature, HDM counts (trap and vacuum samples), HDM allergen, and other details of the home environment were measured on four occasions over a period of 1 year. Interventions and measurements were concerned predominantly with one bedroom. RESULTS: There was a reduction in relative humidity in the dehumidifier group, but not the behavioural group. A decline in HDM trap counts was observed for all three groups. Change scores did not indicate that the dehumidifier group had a greater decline than the other groups. A secondary analysis examining presence or absence of HDM showed a shift from households having HDM at baseline to households not having HDM in the final round for some trap measures. Change score analysis indicated that this shift was greater in the dehumidifier group compared with other groups. The dehumidifier group did not show a greater decline in HDM allergen than that seen in the other two groups. CONCLUSION: Neither the dehumidifier nor the behavioural intervention had a major effect on HDM counts or allergen levels. However, the study did have a number of limitations relating to size, timing of intervention, and running of the dehumidifiers. The secondary data analysis may indicate some effect of dehumidification, but clearly this effect was small. There is a need for more information on the effects of reducing ambient humidity on the distribution of HDM within their habitats.
BACKGROUND: There is considerable evidence that T cells may play an important role in asthma. The purpose of this study was to determine whether the responsiveness of T lymphocytes to mite allergen stimulation in vitro is a determinant of bronchial response to house dust mite (HDM) allergen challenge in subjects who are allergic to HDM. METHODS: Peripheral blood was taken from seven healthy nonatopic subjects and 23 subjects with positive skin test reactions to HDM. Of the subjects in the latter group, 16 had an asthmatic reaction on inhalation challenge with HDM extract (HDM-responders), whereas the remaining seven had a negative reaction (HDM allergic). The proportion of subsets of T lymphocytes and their activation and the amount of IL-2, IL-4, IL-5, and interferon-gamma released in the supernatants with and without stimulation with the HDM extract were determined. RESULTS: Without stimulation, the proportions of subsets of T lymphocytes and their activation were similar between groups. When stimulated with the HDM allergen, the proportion of CD4+CD25+ cells from HDM responders was significantly higher than those in the control group. Comparison within groups of cell cultures with and without stimulation with the mite allergen showed that the proportion of CD4+, CD4+CD25+, CD4+/CD8+, and CD3+HLADR+ cells were significantly increased in HDM responders with stimulation; there was a trend for CD4+CD25+ cells to be increased in the HDM-allergic subjects; no increase in any T-lymphocyte subsets was found in the control subjects. The release of IL-5 was significantly greater in HDM responsers than in the other two groups. The severity of the immediate asthmatic reaction was significantly associated with the degree of nonallergic bronchial hyperresponsiveness and the amount of IL-5 released but not with the level of specific IgE to the mite allergen or subsets of T lymphocytes with and without stimulation. CONCLUSION: The findings suggest that responsiveness of T lymphocytes to allergen challenge in vitro may play a role in determining the bronchial response to the allergen in vivo.
Although the level of house dust mite (HDM)-specific lymphocyte proliferation is high in infants with atopic dermatitis (AD), the level of HDM-specific IgE antibody (HDM-IgE-RAST) is usually very low or negative. To elucidate the cause of the deficient HDM-specific IgE antibody formation in infants with AD, we examined the profile of IL-4 and IFN-gamma production by HDM-stimulated PBMCs. The amount of IL-4 production was higher in infants with AD and in children with AD (3 to 15 years) than in the nonatopic control subjects. Although the amount of IFN-gamma production in children with AD was lower than that found in nonatopic children, it was higher in infants with AD than in nonatopic infants. This result suggests that HDM-specific helper T lymphocytes in infants with AD have not yet differentiated into TH2 but rather stayed at the stage of TH0. The level of IgE-RAST for egg white (EW) is already elevated in infants with AD. The amount of IL-4 produced by EW-stimulated PBMCs was comparable to that produced by HDM-stimulated PBMCs in infants with AD. However, the amount of IFN-gamma produced by EW-stimulated PBMCs was distinctly lower than that produced by HDM-stimulated PBMCs in infants with AD. Although there was no correlation between the amount of IL-4 production by HDM-stimulated PBMCs and the level of HDM-IgE-RAST in infants with AD, the amount of IL-4 production by EW-stimulated PBMCs was closely correlated with the level of EW-IgE-RAST. These results suggest that it is not the lack of IL-4 but rather a relative increase in IFN-gamma production by HDM-specific helper T lymphocytes that causes the deficiency of HDM-specific IgE-antibody synthesis in infants with AD.
In areas with low house dust mite (HDM) allergen exposure, both mite sensitization and asthma prevalence are low. In most other areas, HDM allergen exposure is higher than the threshold for sensitization. In this setting, is HDM allergen exposure a factor which is causally related to the development of asthma in HDM-sensitive individuals? To answer this question, the cumulative prevalence of asthma was evaluated in a group of 157 schoolchildren, aged 10 and 11 yrs, who were allergic to HDM allergen, and compared it with HDM allergen exposure and atopic status, using univariate and multivariate analysis. HDM allergen levels were measured in mattress dust using an enzyme-linked immunosorbent assay (ELISA) method. Of mattress dust samples, 94% had an HDM allergen level >2 microg x g dust(-1). Atopy was evaluated by means of skin prick tests using five common allergens. Among the predictive variables studied by means of univariate analysis, only the number of positive skin tests and male sex correlated with asthma prevalence, but not HDM allergen exposure. Logistic regression analysis also demonstrated that the number of positive skin tests correlated with asthma prevalence (odds ratio (OR)=1.38, p=0.05), whereas the OR for HDM allergen exposure was 1.0. This survey suggests that, in a geographical area with high HDM allergen exposure, asthma prevalence is not linked with HDM allergen levels.
Helodermin (HDM) belongs to the vasoactive intestinal polypeptide (VIP) family of polypeptides. Degradation of HDM in the tracheal tissue isolated from a guinea-pig and by an isolated enkephalinase was studied and compared with the degradation of VIP. The tracheal relaxing activity of VIP was potentiated by enkephalinase inhibitors, thiorphan and phosphoramidon, while the activity of HDM was not potentiated. On the other hand, bestatin, an aminopeptidase inhibitor, and captopril, an angiotensin converting enzyme inhibitor, did not influence the activity of VIP and HDM. The data suggests that the degradation of VIP but not HDM in the trachea was done by enkephalinase. Enkephalinase was then purified from the lung and the striatum membrane fraction through a DEAE-cellulose column, chromatofocusing column and hydroxyapatite column. The purified enkephalinase from the lung hydrolyzed VIP but not HDM. HDM and VIP were, however, hydrolyzed by the striatum enkephalinase. There was only a partial degradation of HDM by the striatum enkephalinase and the hydrolysis rate of HDM was slower than that of VIP. The degradation of VIP and HDM was inhibited by thiorphan. In conclusion, we found that VIP but not HDM was degraded by enkephalinase present in the respiratory system such as the trachea and the lung. Furthermore, enkephalinase, which hydrolyses HDM, was present in the brain.
House dust mite (Hdm) infestation used to be rare in Stockholm, but Hdm-sensitized children are now frequently observed, which probably indicates an increased infestation rate. This study was performed to elucidate determinants of Hdm sensitization in children living in the area. In a case-control study, 53 Hdm-sensitized children (cases), a group of non-Hdm-sensitized atopic children (N = 54), and a group of nonallergic neighborhood children (N = 53) were included. Mattress dust was analyzed with ELISA for content of Hdm allergens. Indoor humidity and temperature were measured, and questionnaire data were collected. Asthma was significantly more common in the Hdm-sensitized group than in the atopic control group. Hdm allergens were found in 40%, 19%, and 23% of the dust samples of the case group, atopic group, and neighborhood control groups, respectively. Only 15% of the dust samples of the Hdm-sensitized children contained Hdm allergens above the recommended threshold levels of sensitization of 2000 ng/gm of dust. Inadequate ventilation, which partly appeared to be a consequence of energy saving, appeared to be a risk factor for Hdm sensitization. This result may apply also to other temperate regions and suggests that the problem is preventable.
Because house dust mite (HDM)-specific IgE antibody (IgE-RAST) is usually not detectable in infants with atopic dermatitis (AD), HDM has not been regarded as the cause of infantile AD. The level of HDM-specific lymphocyte proliferation (expressed as stimulation index measured by flow cytometry [SIF]), however, was found to be markedly elevated in AD infants. This suggests that the sensitization of T cells to HDM extract occurs even in infancy. Moreover, the level of HDM-SIF is correlated closely with the severity of infantile AD, suggesting that HDM is a major cause of this disease not only in adults and children but also in infants. Although the level of HDM-SIF did not correlate with the level of HDM-specific IgE-RAST in infants with AD, it did intimately correlate with the absolute number of peripheral blood eosinophils. Because T lymphocytes are known to secrete some cytokines, such as IL-5, that enhance the proliferation of eosinophils, we measured the IL-5 production by peripheral blood mononuclear cells in infants with AD on stimulation with HDM extract. The amount of IL-5 production is significantly higher in infants with AD, as well as in children with AD, than that found in nonatopic control subjects. Moreover, the level of IL-5 production is correlated closely with the level of HDM-SIF in infants with AD. Taken together, these results suggest that HDMs play an important role in the development of infantile AD by inducing IL-5 production from HDM-specific T lymphocytes.
BACKGROUND: House dust mite (HDM) Dermatophagoides pteronyssinus is the most important source of indoor allergens that cause allergic diseases in Taiwan. We prepared purified HDM allergens (Der p 1, Der p 2 and Der p 5) to detect allergen-specific immunoglobulin (Ig) E responsiveness among a large number of test subjects. The robust genetic typing system for HLA class II genes also facilitated the study on association of HLA and allergic response toward HDM. OBJECTIVE: This study intended to investigate the association between HLA class II alleles and the IgE responsiveness to the major allergens from HDM, D. pteronyssinus. METHODS: Two hundred and forty-eight subjects were selected for HLA association study. Plasma HDM allergen (Der p 1, Der p 2, Der p 5) -specific IgE and Der p 2-specific IgG antibodies were detected by ELISA, while HLA class II -DRB1, -DQA1, -DQB1, -DPB1 genetic polymorphism was determined by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization (PCR/SSOPH). Statistical comparison of the allelic distribution of each HLA class II genes among the individuals with/without HDM allergen-specific IgE and IgG antibodies were performed. RESULTS: There was no significant association between HLA DRB1, DQB1, DQA1 alleles and HDM-specific IgE responsiveness noted. Only DRB1*0803 and the linked DQA1*0103 alleles showed positive association with Der p 5-specific IgE responsiveness. However, we found that HLA-DPB1*1301 predisposed subjects to IgE responsiveness to HDM Der p 5. HLA DPB1*0501 was weakly associated with the IgE responsiveness to HDM Der p 1 and Der p 5. There was a strong negative association between the HLA-DPB1*0201 allele with IgE responsiveness to Der p 1 (OR: 0.30, P </= 0.0001, P </= 0.0007, Pc </= 0.010). CONCLUSION: We clearly observed the association between HLA DPB1 alleles and specific IgE responsiveness to HDM major allergens. The molecular mechanism of HLA-DPB1*0201 involvement in protecting subjects from HDM-specific IgE responsiveness awaits further investigation.
BACKGROUND: Higher house dust mite (HDM) allergen exposure during infancy has been associated with increased HDM sensitization. Infant bedding has been associated with the accumulation of varying levels of HDM. Prospective data on the relationship between infant bedding and the development of HDM sensitization has not been previously examined. OBJECTIVES: To determine if particular types of bedding used in infancy are associated with increased risk of house dust mite sensitization in childhood. METHODS: A population-based sample (n = 498) of children born in 1988 or 1989, and who were resident in Northern Tasmania in 1997, participated in this study. These children were part of a birth cohort study (1988-95), the Tasmanian Infant Health Survey. Data on infant underbedding and mattresses was available on 460 and 457 children, respectively. The main outcome measure was HDM sensitization defined as a skin prick test (SPT) reaction of 3 mm or more to the allergens of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. RESULTS: The use of either sheepskin underbedding or plastic mattress covers in infancy was associated with an increased risk of sensitization to HDM allergens at age 8 years. The adjusted risk ratio (RR) for sensitization to HDM with sheepskin in infancy was 2.27 (95% CI: 1.14, 4.55), P = 0.020. The adjusted RR for sensitization to HDM with the use of plastic mattress covers in infancy was 2.06 (95% CI: 1.22, 3.51), P = 0.007. The use of a foam mattress in infancy was not related to subsequent HDM sensitization. CONCLUSION: Infant's bedding plays a role in the development of HDM sensitization in childhood. Intervention studies to examine mite allergen levels and the role of underbedding on the development of HDM sensitization are required.
The scabies mite Sarcoptes scabiei and the Dermatophagoides house dust mites (HDM) are related phylogenetically and are the sources of several cross-reactive antigens. The purpose of this study was to investigate the immune response to S. scabiei and HDM in scabietic patients. Skin test sensitivity and serum IgE to both S. scabiei and HDM were determined for patients who had or previously had confirmed ordinary scabies. A retrospective group included nine subjects who had received successful treatment three weeks to one year prior to the study. A prospective group included 16 subjects with active scabies. Allergic histories were obtained, serum was collected, and skin prick tests (SPTs) were performed at enrollment for all and periodically over the next 12 months for the prospective patients. None of the individuals in either group reported a known sensitivity to HDM. Six of the nine retrospective patients were SPT positive to both S. scabiei and HDM and two of these showed circulating IgE specific for these antigens. At diagnosis, 13 of 16 patients with active scabies were SPT positive to S. scabiei and 12 of these were also SPT and/or radioallergosorbent test positive to HDM. Six patients had circulating IgE directed at both S. scabiei and HDM antigens while one subject had IgE to S. scabiei only and another had IgE directed at HDM only. Twelve of the 15 subjects tested also showed IgE and/or IgG binding to one or more bands on Western blots of an S. scabiei-specific protein fraction. This study indicated that approximately half of the patients with active scabies had S. scabiei- and HDM-specific circulating IgE while most patients cured of scabies lacked S. scabiei- and HDM-specific serum IgE. The data also suggested that antibodies to S. scabiei in scabietic patients also recognize HDM; however, some antibodies were directed at scabies-specific antigens.
BACKGROUND: Modified allergen extracts (allergoids) with reduced IgE-binding capacity are successfully used in immunotherapy of atopic allergy. Their reduced T-cell stimulatory capacity is less well studied and is a subject of the present study. METHODS: We compared the ability of native house dust mite extract (Dermatophagoides pteronyssinus; HDM) and the glutaraldehyde-modified allergoid (HDM-GA) to induce the proliferation and cytokine production by fresh PBMC and by DC-stimulated polyclonal Th cells and HDM-specific Th cell clones. RESULTS: Freshly isolated T cells showed a partially reduced responsiveness to HDM-GA, differentially pronounced in different donors. HDM-specific Th cell clones prepared from three donors showed either a complete loss of reactivity to HDM-GA, or completely preserved responsiveness. The frequency of nonreactive clones was donor-dependent (2/3, 3/10 and 1/10). GA modification of HDM did not interfere with the cytokine production profile of HDM-specific T cell clones. CONCLUSIONS: The reduced stimulatory potential of HDM-GA results mainly from a loss of certain Th cell epitopes, rather than impaired allergen uptake and presentation, or induction of suppressive factors. Varying frequencies of allergoid-nonreactive HDM-specific Th cells may result in differential responses of individual patients to immunotherapy.
BACKGROUND: Allergen-specific IgE antibodies have been considered to play an important role in the pathogenesis of atopic asthma. However, studies on allergen-specific IgE antibodies in airway secretion from asthmatic patients are very rare compared with those in serum. OBJECTIVES: The present study was undertaken to determine whether induced sputum might provide a useful method for analysing allergen-specific IgE antibodies in airway secretions from asthmatic patients. METHODS: Specific IgE antibodies to house dust mite (HDM) antigen were measured in induced sputum from 10 HDM-sensitive asthmatic patients and 12 non-allergic controls by enzyme-linked immunosorbent assay. HDM-specific IgE was regarded as positive when the absorbance value was higher than mean + 2SD of controls. Their antigen-binding characteristics were determined by immunoblot analysis. RESULTS: HDM-specific IgE was positive in induced sputum from seven of 10 HDM-sensitive asthmatics. The IgE binding to HDM antigen could be inhibited by fluid phase HDM antigen in a dose-dependent manner, not by mugwort antigen. Treatment of induced sputum with dithiothreitol decreased the antigen-specific bindings, and increased the non-specific bindings on the measurement of HDM-specific IgE. These effects were significant in a concentration of dithiothreitol greater than 0.05%. Immunoblot analysis revealed that HDM-specific IgE antibodies in induced sputum recognized the HDM antigens with molecular weights of 42, 34, 32, 25 and 14 kDa. These antigen binding characteristics were similar to those in serum. CONCLUSION: We conclude that analysis of induced sputum is a useful non-invasive method for studying allergen-specific IgE antibodies in airway secretion from asthmatic patients.