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PubMed2004

The characteristics of patients with atopic dermatitis demonstrating a positive reaction in a scratch test after 48 hours against house dust mite antigen.

The clinical characteristics of patients in whom an IgE-mediated reaction against house dust mite (HDM) antigens that contribute to the pathogenesis of atopic dermatitis (AD) remain unclear. This study attempted to elucidate the characteristics of patients who exhibit a positive reaction 48 hr or later against HDM in scratch tests. The reactions after epi-cutaneous application of the allergen to skin with prior scratching were observed for one week in sixteen AD patients showing positive immediate-type hypersensitivity reactions for HDM. Fifty percent of the patients demonstrated positive reactions at 48 hours after epi-cutaneous application of HDM. Significantly higher values were demonstrated in the group positive for HDM after 48 h in serum total IgE, specific IgE for Der f 1, and lactate dehydrogenase, peripheral eosinophil counts, eruption score, and the area of eruption than in the group negative for HDM after 48 h. Domestic exposure to Der f 1 was also higher in the group positive for HDM after 48 h than in the negative group. These results indicate that the patients in whom the HDM-induced reaction continuing more than 48 h and contributing to their real eczematous eruptions are characterized by considerably increased levels of specific IgE for HDM antigens, high disease activity in AD, and increased exposure to domestic HDM.

Adolescent↗

PubMed1987

Polycation binding to glomerular basement membrane. Effect of biochemical modification.

The polycation hexadimethrine (HDM) binds to anionic sites in the glomerular basement membrane (GBM) and causes heavy proteinuria when infused in vivo. An in vitro assay of 3H-HDM binding to isolated dog GBM was developed, to permit further analysis of the GBM components binding HDM. 3H-HDM binding to isolated GBM was saturable, reversible in dose-dependent fashion by competing polycations, and inhibited by increasing salt concentration and low pH. The pH dependence of binding suggested that most of the HDM binds to carboxyl groups rather than to the sulfate groups of proteoglycans. Removal of heparan sulfate by heparinase or purified heparatinase had no detectable effect on HDM binding. Treatment of GBM with neuraminidase, hyaluronidase, or chondroitinase reduced binding of HDM by a maximum of 20 to 38%. However, substitution of carboxyl anions with nonionizable glycine methyl ester residues resulted in complete elimination of HDM binding. Parallel results were obtained in studies of glomerular localization of cationized ferritin (CatF), pI 8.5. After carboxyl substitution, GBM did not bind CatF; heparinase-treated GBM bound CatF in a distribution not demonstrably different from normal. Cellulose acetate electrophoresis of glycosaminoglycan fractions prepared from treated GBM confirmed that carboxyl modification did not alter the content or charge of the heparan sulfate of GBM, but heparinase treatment removed at least 90% of heparan sulfate. The results indicate that carboxyl groups are quantitatively more important than heparan sulfate for binding of HDM in vitro. Since HDM causes proteinuria in vivo, carboxyl groups may be important for maintenance of normal permselectivity.

Animals↗

PubMed1984

Stainable glomerular basement membrane polyanions and renal hemodynamics during hexadimethrine-induced proteinuria.

To clarify the mechanism of hexadimethrine-induced proteinuria, we studied the changes in stainable glomerular basement membrane anions and renal hemodynamics during hexadimethrine (HDM) infusion. To determine whether glomerular anions were neutralized in vivo, animals infused with HDM received cationized ferritin intravenously, or their kidneys were perfused in situ with lysozyme. During its infusion, HDM bound heavily within the glomerular basement membrane, and binding of the cationic probes was virtually abolished. During recovery after HDM infusion, HDM deposits diminished and the binding of the cationic probes recovered to normal. The inverse correlation between HDM binding and binding of the cationic probes confirms that the glomerular binding of HDM is associated with neutralization or shielding of the glomerular basement membrane anions in vivo. Renal hemodynamic parameters and urinary protein excretion rate were measured before, during, and after infusion of HDM. Heavy proteinuria appeared during HDM infusion and persisted for 1 hour after its discontinuation. Although glomerular filtration rate, renal plasma flow, and urine flow rate decreased transiently at the onset of proteinuria, they returned to baseline levels before resolution of proteinuria. Filtration fraction never changed significantly. Thus, proteinuria cannot be attributed solely to renal hemodynamic factors. These results strengthen our hypothesis that HDM induces proteinuria as a consequence of its binding to and neutralization of glomerular basement membrane fixed anions.

Animals↗

PubMed1996

Role of CD34+ cells in engraftment after high-dose melphalan in multiple myeloma patients given peripheral blood stem cell rescue.

During the period December 1992 to June 1995, 95 patients were treated with high-dose melphalan (HDM) with peripheral blood stem cell rescue (PBSCR). Sixty-five had received previous treatment and 28 had relapsed. Among patients who had relapsed 21/28 had received HDM previously including one who received HDM twice during the course of the study. Seventy-five patients were given HDM/PBSCR for the first time. Comparisons have been made between engraftment times for platelets and neutrophils among patients who received less than or greater than 2 x 10(6) CD34+ cells at rescue. Analyses have also been done to evaluate the effect of previous HDM on recovery. Mobilization of progenitor cells was done with granulocyte colony-stimulating factor (G-CSF). Patients received only PBSCR. No growth factors were given to the PBSCR recipients during the recovery period. The percentage of patients from whom the number of CD34+ cells mobilized was > 2 x 10(6)/kg was similar in patients who received HDM for the first time (23%) compared with those who had had it previously (19%). The yield of CD34+ cells correlated with the number of granulocyte-macrophage colony forming units (CFU-GM). Although the number of CD34+ cells infused was < 2 x 10(6)/kg in 77% of patients, all engrafted for neutrophils to > 0.5 x 10(9)/l. This was delayed in patients who had had previous HDM (P < 0.02). Platelet recovery to > 25, 50 and 100 x 10(9)/l was delayed in all patients who received < 2 x 10(6) CD34+ cells/kg infused (P < 0.02). In patients who had had previous HDM both neutrophil (P < 0.05) and platelet recovery (P < 0.007) were delayed compared with recovery in patients who had not had HDM. In patients who had had previous HDM and received < 2 x 10(6) CD34+ cells/kg infused only 3/17 regained platelets to > 100 x 10(9)/l compared with 3/4 who had > 2 x 10(6) CD34+ cells/kg infused (P < 0.05 Fisher's exact test). There was no evidence that low numbers of CD34+ cells in the PBSCR were associated with early death. The data show that previous treatment with HDM had adverse effects on the subsequent engraftment of platelets among patients given HDM/PBSCR. The data suggest that additional measures are needed to achieve platelet reconstitution in these heavily pre-treated patients.

Antigens, CD34↗

PubMed1989

Effects of a synthetic cationic polymer on sodium and potassium currents of frog nerve fibres.

(1) Voltage-clamped nerve fibres of the frog Rana esculenta were treated with the synthetic cationic polymer hexadimethrine bromide (HDM) [Polybrene]. (2) 1 microM HDM irreversibly reduced INa to about 65% of its original size. The time to peak remained almost unaffected, while the decaying phase of the currents (for pulse potentials less than -10 mV) became accelerated. The size of INa was hardly reduced further even with a 1,000-fold higher concentration of HDM. (3) The cationic polymer HDM was without effect on the voltage-dependence of activation and there was only a small shift (-4.5 mV) of the voltage dependence of steady-state inactivation. (4) Variation of [Ca2+] in the Ringer solution shifted the voltage-dependence of activation and of steady-state inactivation to the same extent before and after treatment with HDM. By contrast, 0.5 mM La3+ markedly decreased the Ca2+-induced shifts. (5) The decrease of the size of INa by increasing [Ca2+] was strongly reduced by HDM, as well as by the presence of La3+. (6) These results suggest, that HDM is bound irreversibly to Ca2+ and La3+ binding sites of the membrane that affect the size of INa. These sites are different from Ca2+ (or La3+) binding sites acting on the gating mechanism. (7) The potassium currents were also irreversibly reduced by HDM-treatment. This effect, however, was different for inward and outward currents; for inward currents the IK remaining was about 20% of its original size, while for outward currents IK was reduced only to about 65%. The time course of activation of IK was not affected by HDM-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2000

IL-4 production by PBMCs on stimulation with mite allergen is correlated with the level of serum IgE antibody against mite in children with bronchial asthma.

BACKGROUND: Although IL-4, IL-13, and IFN-gamma are known to affect IgE synthesis, it remains unclear which one plays the most important role in in vivo IgE synthesis in atopic patients. OBJECTIVE: The aim of this study is to clarify the difference in importance among these cytokines in up-regulation of IgE synthesis in atopic patients. METHODS: We measured IL-4, IL-13, and IFN-gamma production by PBMCs on stimulation with house dust mite (HDM) in 23 children, 3 to 15 years old, with bronchial asthma (BA) and analyzed the correlation with HDM-specific IgE antibody levels expressed as HDM IgE radioallergosorbent test (RAST) results. RESULTS: The production of IL-4 and IL-13 by PBMCs on stimulation with HDM was significantly higher in children with BA than in nonatopic control subjects (IL-4, 752.9 +/- 365.9 vs 312.3 +/- 230.0 fg/mL, P <.001; IL-13, 21.9 pg/ml [<12.0-77.6] vs <12.0, P <.01). IL-4 production showed a close positive correlation with HDM IgE RAST (r = 0.71, P <.001), which was distinctly stronger than that between IL-13 production and HDM IgE RAST (r = 0.46, P <.05). IFN-gamma production was neither different between children with BA and nonatopic control subjects (7. 24 [1.54-33.90] pg/mL vs 11.2 [1.66-75.9] pg/mL) nor correlated with HDM IgE RAST levels. Essentially the same result was obtained by stimulation of PBMCs with a purified HDM major allergen Der f 1. CONCLUSION: IL-4 is likely to be the most important cytokine in up-regulation of in vivo IgE synthesis against HDM in children with BA.

Adolescent↗

PubMed1998

Association between Der p 1 concentration and peak expiratory flow rate in children with wheeze: a longitudinal analysis.

BACKGROUND: House dust mite (HDM) allergen exposure has been well documented as an environmental cause of airway hyperresponsiveness (AHR) and asthma symptoms. The relationship between asthma morbidity and exposure to low concentrations of HDM allergen suggests that there may be no safe exposure threshold to HDM allergen. OBJECTIVE: We aimed to investigate the associations between Der p 1 in bedding and lung function in 30 children with a history of wheezing in a longitudinal study. METHODS: After a cross-sectional study of school children, which included histamine challenge for AHR and skin testing for dust mite atopy, we made repeated measurements of HDM allergens in children with a history of wheeze over a 12-month period. These children also kept a daily asthma diary in which they recorded their peak expiratory flow rates (PEFRs). We used a repeated measures model to determine the association between PEFR and HDM allergen concentration. RESULTS: There was a significant association between PEFRs and HDM allergen concentration (beta-coefficient = -14.17, P = .0024) in children with HDM atopy. An association was not found in children without HDM atopy. CONCLUSIONS: These findings support the hypothesis that HDM allergens have an adverse effect on the lung function of children with wheeze and highlight the importance of maintaining low dust mite allergen levels throughout the year in the home environment of children sensitized to HDMs.

Allergens↗

PubMed1999

Sensitization to allergens of house-dust mite in adults with atopic dermatitis in a cold temperature region.

BACKGROUND: An IgE-mediated contact reaction to airborne allergens has been suggested as one important pathogenetic mechanism in atopic dermatitis (AD). The house-dust mite (HDM) might be a common allergen involved. In Scandinavia, sensitization to HDM has been rare, probably because of the cold, dry climate. However, recent studies indicate high levels of domestic mites and HDM allergen in 15-20% of homes in central and northern Sweden. METHODS: To evaluate the importance of the HDM in patients with AD in the Stockholm region, we screened 81 adult Stockholm residents with AD, for the prevalence and degree of sensitization to the HDM, according to specific IgE (RAST), skin prick test (SPT), and atopy patch test (APT). We also assessed the HDM exposure in their homes and correlated the results with clinical history, severity of the dermatitis, and type of residence during childhood and today. RESULTS: The sensitization rate to HDM was high (56% according to RAST, 24% according to SPT, and 47% according to APT), and 20% of the patients were exposed to HDM allergens in their beds. Mite exposure seemed to aggravate the dermatitis in highly sensitized patients. CONCLUSIONS: The results indicate that we have to take the HDM into account when discussing aggravating factors in adult patients with AD in the Stockholm region.

Adolescent↗

PubMed2001

Effectiveness of occlusive bedding in the treatment of atopic dermatitis--a placebo-controlled trial of 12 months' duration.

BACKGROUND: Several studies on avoidance of house-dust-mite (HDM) and cat allergens have been carried out, most of them in asthmatic patients and only a few in patients with atopic dermatitis (AD). No study so far has focused on which subgroup of AD patients benefits from avoidance measures. METHODS: Forty adult patients with AD completed the 12-month avoidance study. They were divided into an active treatment (n = 22) and a placebo (n = 18) group. Active treatment comprised use of polyurethane-coated cotton encasings for bedding, and placebo use of cotton covers. Patients came for regular checkups during the 12-month period, when eczema severity was assessed and blood samples were analyzed for total IgE, HDM- and cat-specific IgE and soluble CD30 (sCD30) in serum. Dust samples were collected from mattresses before treatment and after 3, 6, and 12 months, and analyzed for content of HDM and cat allergen. RESULTS: Eczema severity decreased significantly in both groups (P < 0.001), with a more pronounced decrease in patients with active covers. The HDM exposure decreased significantly in the active treatment group (P < 0.001), and the levels of HDM-specific IgE were reduced (P<0.05). Exposure to cat allergens was unchanged in the active treatment group but decreased, albeit not significantly (P=0.19), in the placebo group. sCD30 levels were significantly reduced in both groups (P<0.001). Patients not sensitized to HDM allergens benefited from the bedcovers as much as sensitized patients. CONCLUSIONS: Occlusive bedding significantly reduced HDM exposure in bed (P<0.001) and eczema severity, and sCD30 levels decreased significantly (P<0.001). Patients not sensitized to HDM and not exposed to HDM allergens benefited equally from use of the bedcovers, a result which could be due to a reduction of other important allergens, superantigens, or irritants in bed. We therefore recommend the use of bedcovers as part of treatment for AD.

Adult↗

PubMed1997

Seasonal differences in airway hyperresponsiveness in asthmatic patients: relationship with allergen exposure and sensitization to house dust mites.

BACKGROUND: The degree of airway hyperresponsiveness in allergic asthmatic patients may be influenced by changes in environmental exposure to inhalant allergens. OBJECTIVE: This study investigates the relationship between seasonal changes in exposure to house dust mite (HDM) allergens and non-specific airway hyperresponsiveness in asthmatic patients with multiple sensitizations to inhaled allergens. METHODS: In 43 asthmatic patients sensitized to several inhalant allergens, lung function (FEV1), airway hyperresponsiveness (PC20 histamine), serum total IgE, house dust mite (HDM) specific IgE and number of peripheral blood eosinophils were measured during autumn 1990 (September-November) and spring 1991 (March-May). During each season, floor dust samples were collected twice from living- and bedrooms and the concentration of the HDM allergens Der p 1 and Der p 2 determined. RESULTS: More severe airway hyperresponsiveness (lower PC20 histamine) during autumn was only found in patients sensitized to HDM (n = 32; autumn: 2.05 mg/mL, spring: 4.51 mg/mL (geometric means), P < 0.01), whereas in patients not sensitized to HDM (n = 11) similar values were observed in both seasons (3.44 and 4.52 mg/mL, respectively, P = 0.56). More severe airway hyperresponsiveness of HDM sensitized patients in autumn was significantly associated with higher Der p 1 concentrations in floor dust. Aside from airway hyperresponsiveness, seasonal changes in serum total IgE and number of peripheral blood eosinophils were seen in patients sensitized to HDM. CONCLUSIONS: In allergic asthmatic patients, airway hyperresponsiveness may increase during autumn, depending on sensitization to HDM and an increase of exposure to HDM allergen.

Adolescent↗

PubMed1998

Comparison between the in vitro cytokine production of mononuclear cells of young asthmatics with and without immunotherapy (IT)

BACKGROUND: The underlying mechanisms of immunotherapy (IT) are still unknown but may be related to modifications of cytokine production of T lymphocytes. OBJECTIVE: In this study we determined the in vitro allergen-induced production of IL-2, IL-4, IL-5, IL-12 and IFNgamma of peripheral blood mononuclear cells (PBMC) of eight young asthmatics, aged 15+/-2 years, receiving IT (IT group) and of eight comparable asthmatics, aged 13+/-3.5 years, who never received IT (non-IT group). METHODS: All patients suffered from perennial asthma and were allergic to house dust mite (HDM). They were selected if they showed a positive stimulation index (SI) of PBMC after in vitro incubation with HDM (i.e. SI > 2). Cells were incubated with and without HDM (10 microg/mL) during 24 h, 48 h and 7 days. Cytokines were determined in the supernatant at the three time points and are expressed as median values in pg/mL. RESULTS: In the IT group the secretion of IL-2 was lower compared with the non-IT group after 7 days incubation of PBMC with HDM (0 vs 33.2, P = 0.008). In both groups maximal secretion of IL-2 was observed after 48 h. In the non-IT group a high value of IL-2 persisted after 7 days, whereas in the IT group a significant decline of IL-2 occurred after 7 days. Although IL-4 secretion was low in all subjects, more patients of the non-IT group showed detectable IL-4 in the HDM cultures after 24 h and 48 h, although the difference was not statistically significant (P = 0.08 and P = 0.28, respectively). Furthermore, IL-4 secretion was lower in the HDM cultures after 24 h in the IT group (1.75 vs 4.1, P = 0.011) and 48 h (2.2 vs 4.1, P=0.035). IL-5 secretion was lower in the HDM cultures after 24h (12.4 vs 47.6, P = 0.035) and 48 h (26.8 vs 135, P = 0.046) in the IT group than in the non-IT group. After 7 days of incubation with HDM there was no difference between the groups. There was no difference between both groups in secretion of IFNgamma and IL-12. CONCLUSIONS: These results show a difference in vitro cytokine secretion of PBMC of asthmatics receiving IT compared with asthmatics who never received IT. PBMC of patients receiving IT secrete less IL-2 and IL-5 after in vitro incubation with HDM and show a tendency to secrete less IL-4. The efficacy of IT may be attributed to a modified cytokine secretion of PBMC.

Allergens↗

PubMed2001

Interaction of cigarette smoke and house dust mite allergens on inflammatory mediator release from primary cultures of human bronchial epithelial cells.

Several studies have shown that exposure to cigarette smoke and/or house dust mite (HDM) can lead to increased airway inflammation in susceptible individuals. The underlying mechanisms, however, are not defined. To investigate the interaction between cigarette smoke and HDM allergen on mediator release from primary cultures of human bronchial epithelial cells. Confluent human bronchial epithelial cell cultures were exposed to cigarette smoke in the absence or presence of HDM allergen and investigated for the release of IL-8, IL-1beta, and sICAM-1. Damage to the epithelial cells themselves was assessed by release of 51Cr. On separate occasions, we investigated the effect of PTL11028, a highly potent and selective Der p1 inhibitor, on HDM allergen-induced release of IL-8, following activation of HDM allergen by incubation with cysteine. The effect of cigarette smoke exposure on the stability of these released mediators in prepared solutions in the absence/presence of reduced glutathione was also studied. Both HDM allergens and short-term (20 min) cigarette smoke exposure led to a significantly increased release of IL-8, IL-1beta and sICAM-1 from the epithelial cell cultures. Longer exposure (1-6 h) to cigarette smoke led to a dramatic decrease in the amount of these mediators detected in the culture medium. Whilst incubation of epithelial cultures with HDM allergen did not cause any significant change in the release of 51Cr from pre-loaded cells, cigarette smoke on its own led to a marked, exposure and incubation-time dependent increase in the release of 51Cr. Incubation with HDM allergen led to a significant, dose and time-dependent increase in the release of IL-8, which was further enhanced when the allergen extract was pre-activated with cysteine. This effect was completely abrogated by PTL11028, a novel Der p1 inhibitor. Prepared solutions of various concentrations of IL-8, IL-1beta and sICAM-1 exposed to cigarette smoke demonstrated a dramatic exposure time-dependent decrease in the detectable amount of these mediators, an effect which was abrogated by GSH. HDM-induced airway inflammation may include Der p-mediated release of inflammatory mediators from epithelial cells. Additionally, short-term cigarette smoke exposure may induce airway inflammation by release of inflammatory mediators from these cells, an effect which may be potentiated by Der p allergens. Longer term cigarette smoke exposure may cause damage to epithelial cells and changes in the structure of inflammatory mediators.

Aged↗

PubMed1998

Accuracy and precision of access recirculation measurements by the hemodynamic recirculation monitor.

The hemodynamic monitor (HDM) is a device that uses magnetic principles to accurately measure access recirculation during hemodialysis. The measurement is based on differential conductivity between arterial and venous blood flow rates in the dialysis blood tubing sets. One milliliter of hypertonic saline is injected into the venous line of the blood tubing set as a conductivity "tracer." As the tracer enters the patient, the presence of access recirculation causes a percentage of the hypertonic saline to recirculate into the arterial line and is detected and quantified by the HDM; the percentage of access recirculation is calculated in under 1 minute. Clinical studies were performed in two centers on 106 patients with various forms of blood access (eg, arteriovenous fistulae, Gore-tex grafts [WL Gore and Associates, Flagstaff, AZ], Permcaths [Quinton Instrument Co, Bothell, WA], subclavian catheters). Access recirculation was detected under routine dialysis conditions in only 13 patients. In the remaining cases, attempts at inducing access recirculation were made by reversing the arterial and venous lines and/or increasing the blood pump to its maximum sustainable rate for a given patient. A 15-minute protocol was then instituted. Three blood samples (arterial, venous, and "peripheral" [stop-flow technique]) were first obtained to determine urea measurements and for subsequent calculation of access recirculation; immediately afterward, an HDM recirculation measurement was recorded to allow correlation of urea and HDM access recirculation results (accuracy). Two further HDM access recirculation measurements were made to analyze the precision or repeatability of the HDM test. This protocol was attempted up to three times in each patient on different dialysis days. Two hundred fifty-nine studies were made, and a strong linear correlation was obtained between urea and HDM results (r = 0.94, slope 0.95) over a range of access recirculation (5% to 60%) demonstrating accuracy. Repeated HDM access recirculation results showed a characteristic SD of 1.8% over the whole range of values, demonstrating a precision superior to the 6% expected using the urea method. When zero access recirculation was indicated by the HDM, "ground truth" tests were performed by injecting 1 mL of hypertonic saline (HS) into one injection port of the blood tubing set then 0.1 mL of HS into the other to simulate 10% access recirculation; the mean results were 9.96%+/-1.59% (+/-SD; n = 93), confirming the accuracy of the method.

Arteriovenous Shunt, Surgical↗

PubMed2002

Polyclonal and allergen-induced cytokine responses in adults with asthma: resolution of asthma is associated with normalization of IFN-gamma responses.

BACKGROUND: Atopic disease is associated with skewing of immune responses away from a T(H)1 toward a T(H)2 profile. Previous studies have implicated this cytokine imbalance in the development of disease. However, it is not known whether normalization of this imbalance is conversely associated with disease resolution. OBJECTIVE: To further delineate the role of reduced T(H)1 and increased T(H)2 cytokine production in the pathogenesis of atopic disease and to determine whether disease resolution is associated with alteration of cytokine profiles, we investigated cytokine responses in a cohort of adult patients with asthma followed from childhood. METHODS: A cohort of wheezy children and control subjects aged 7 to 10 years were recruited from 1964 to 1967. Subjects were reevaluated every 7 years to monitor the outcome of childhood asthma. At the 42-year follow-up, 89 subjects from this cohort were evaluated for mitogen and house dust mite (HDM)-induced T(H)1 (IFN-gamma) and T(H)2 (IL-4, IL-5, and IL-13) cytokine responses. Cytokine responses were compared in patients with ongoing asthma, patients with resolved asthma, and control subjects. RESULTS: Patients with severe ongoing asthma had significantly reduced HDM-induced IFN-gamma production compared with that of control subjects and patients with resolved asthma. In contrast, HDM-induced IFN-gamma production in patients with resolved asthma was equivalent to that seen in control subjects. Patients with ongoing and resolved asthma produced significantly higher levels of IL-5 in response to HDM compared with that seen in control subjects, with levels being equivalent in patients with active and resolved asthma. HDM-induced IL-13 production was significantly increased in the patients with resolved asthma when compared with that seen in the control subjects. PHA-induced cytokine responses did not parallel HDM-induced responses. CONCLUSION: Patients with persistent and severe atopic asthma have a reduced HDM-induced T(H)1 response, whereas those with resolved asthma do not. This suggests that reduced HDM-induced IFN-gamma production might be an important factor contributing to ongoing severe asthma and that normalization of allergen-induced T(H)1 responses might be important for disease resolution. The finding that all subjects with a history of asthma displayed increased HDM-induced T(H)2 (IL-5 and IL-13) cytokine responses, irrespective of the presence or absence of asthma, suggests that increased T(H)2 responses reflect the presence of the atopic state per se rather than being specifically linked to asthma.

Adult↗

PubMed2001

Dual symptomatic and exudative nasal responses are not characteristics of perennial allergic rhinitis.

Acute and late phase (dual) symptomatic responses after allergen challenge commonly occur in allergic asthma. The aim of the present study was to explore the occurrence of allergen challenge-induced biphasic responses in patients with chronic perennial allergic rhinitis living in an area with high house dust mite (HDM) exposure. Fifteen patients with perennial rhinitis and evident allergy to HDM participated. Nasal challenges with HDM and sham were performed on separate days in a crossover design. Nasal symptoms, forced expiratory volume in 1 s (FEV1) and orally exhaled nitric oxide were recorded every hour for up to 8 h after each challenge. Alpha2-macroglobulin and eosinophil cationic protein (ECP) were analysed in hourly nasal lavages, and nasal histamine provocations were carried out after 8 h. HDM, but not sham, caused an immediate increase in nasal symptoms which gradually abated over the 8-h period. No reoccurrence of nasal late phase symptoms was seen. HDM, but not sham, induced an early increase in alpha2-macroglobulin and ECP levels: both indices remained elevated for up to 3 h after challenge. HDM challenge evoked hyper-responsiveness to histamine expressed as increased nasal symptoms (p < 0.05; HDM vs sham). No differences in exhaled nitric oxide or FEV1 were demonstrated at any one time point between the HDM- and sham-challenged days. It is concluded that nasal symptomatic and exudative late phase responses may not be a general feature, even in subjects with perennial rhinitis challenged with high, symptom-provoking, doses of HDM allergen.

Adolescent↗

PubMed1993

Randomized comparison of the antiemetic efficacy of a serotonin type 3 receptor antagonist (MDL 72,222) with a high-dose metoclopramide regimen.

This pilot randomized study compared MDL 72,222, a highly selective 5-HT3 receptor antagonist, with a high-dose metoclopramide regimen (HDM) for chemotherapy-induced nausea and vomiting. MDL 72,222 was given in 20 mg intravenous doses 30 minutes before chemotherapy, as well as 2, 6, and 12 hours after chemotherapy infusion. The HDM was composed of diphenhydramine 50 mg i.v., metoclopramide 2 mg/kg i.v., and lorazepam 0.04 mg/kg i.v. administered 30 minutes before chemotherapy and 2, 4, 6, and 8 hours after chemotherapy. Patients were randomized to either MDL 72,222 (n = 12) or the HDM (n = 12) and were matched for age, weight, Karnofsky performance status, and chemotherapy. More patients in the MDL 72,222 group had received prior cisplatin. The MDL 72,222 group and the HDM group received a mean cisplatin dose of 66 mg/m2 and 62 mg/m2, respectively. Patients were observed for retching and/or emesis for 24 hours and completed a visual analog scale (VAS) for nausea. Six MDL 72,222 and five HDM patients had no vomiting. One MDL 72,222 and two HDM patients had one episode of emesis within 24 hours of chemotherapy. The median number of emetic episodes in the first 24 hours was 0.5 for MDL 72,222 and 1.0 for HDM patients. HDM patients were frequently asleep and were not awakened for evaluation of nausea with the VAS; 58% (70 of 120) of the HDM (mean score: 19.1 mm) and 14% (17 of 119) of the MDL 72,222 (mean score: 17.1) patients could not have VAS scores obtained (X2 = 50.74, p < 0.001). MDL 72,222 had similar efficacy with less sedation, and further trials are warranted.

Adult↗

PubMedDate not supplied

Estimation of hemodialysis access blood flow rates by a urea method is a poor predictor of access outcome.

Blood flow in peripheral arteriovenous fistulae and grafts as used for hemodialysis access can be derived from simultaneous measurements of 1) the amount of access recirculation (AR) induced by reversing the dialysis blood lines, and 2) the dialyzer blood flow rate (Qb). The hemodynamic monitor (HDM) uses magnetic principles to measure AR. The measurement is based on differential conductivity between arterial (A) and venous (V) blood flows in the dialysis blood tubing sets after the injection of hypertonic saline into the V line as a conductivity tracer. Access blood flow rates (Qa) derived from AR measurements by the HDM are predictive of access outcome. The measurement of AR is traditionally done from the comparison of urea levels simultaneously taken from the A and V blood lines and from the systemic circulation. Thus, the urea method can also be used to estimate access blood flow rates. The purpose of this study was to determine whether urea based Qa values are also predictive of outcome. Forty-one patients with arteriovenous fistulae (n = 25) or Gore-Tex grafts (n = 16) were studied by a standard protocol. The protocol involved temporarily reversing the A and V lines, taking three blood samples for urea estimation, performing an HDM recirculation test, and recording Qb as per the machine blood pump setting. The data allowed calculation of Qa by the HDM (Qa [HDM]) and urea (Qa [urea]) methods. Qa (HDM) was 1,177 +/- 887 ml/min (mean +/- standard deviation) and Qa (urea) 964 +/- 793 ml/min, a statistically significant difference (paired t-test p < 0.001). There was a significant linear correlation between the results (r = 0.94, p < 0.0001), but the regression equation also showed that Qa (urea) values were less than Qa (HDM). The influence of the Qa value on access outcome was determined after an 8 month follow-up. Nine of the 41 accesses were lost to clotting. Chi-square and discriminate analyses showed that Qa (HDM) significantly (p = 0.005) predicted access outcome, whereas Qa (urea) did not (p = 0.164). The specificity of a low Qa (HDM) in predicting access clotting was 0.78, compared with 0.62 for Qa (urea). The data show that although Qa can be estimated by the urea method, the finding of a low Qa (urea) is a poor predictor of access outcome and may lead to cost ineffective investigations.

Arteriovenous Shunt, Surgical↗

PubMed1998

Cross-reactivity between terrestrial snails (Helix species) and house-dust mite (Dermatophagoides pteronyssinus). I. In vivo study.

Clinical reports have suggested an unusual frequency in the number of patients with food allergy to snails who are also allergic to the house-dust mite (HDM). As allergy to HDM is one of the most frequent sensitizations in atopic patients of Western countries, evaluation of the relevance of the concomitant sensitization to Dermatophagoides pteronyssinus and to snails is an important consideration. To evaluate the responsibility of different snail components and of snail mites for inducing in vivo hypersensitivity in patients allergic to HDM, the in vivo reactivity of patients with clinical symptoms after ingestion of snails was assessed by skin prick tests with extracts and hemolymph from four different Helix species snails, and extracts from the snail parasitic mite, Riccardoella limacum. In addition, to obtain epidemiologic data on cosensitization to HDM and snails in allergic patients, the frequency of snail sensitization and its relationship to HDM sensitization were determined in a population of 169 allergic children. All patients allergic to snails had positive skin prick tests to the snail extracts and none to R. limacum extract. The number of positive skin reactions did not significantly differ whatever the species, snail part, or heating procedure used. The strongest reactions were obtained with Helix pomatia (Burgundy snail). Among the 169 prospectively tested children, 38 had a positive prick test to snail extracts; 79% of the snail-sensitized children had sensitization to HDM; and 31% of the children allergic to HDM were found to be sensitized to snails. These results show that snail components, and not the mite R. limacum, were responsible for the in vivo hypersensitivity. These snail components reacting in vivo are present in different parts of snails, including the hemolymph. One-third of the children allergic to HDM were sensitized to snails without any previous ingestion of snails: this observation suggests that HDM was the sensitizing agent and that the cross-reaction could be clinically relevant in countries where eating snails is common.

Adolescent↗