Complications of intra-aortic balloon pump use: does the final position of the IABP tip matter?

We report results of a retrospective review of intra-aortic balloon pump (IABP) use in two Australasian centres and evaluate the effect of final IABP tip position on outcome. Indications for counterpulsation, patient demographics and in-hospital outcomes and complications were retrospectively collected. The chest X-ray reports provided the 'final' position of the IABP tip. The position was defined as acceptable (tip was seen just below the aortic arch, at T2-T5 vertebrae), malpositioned (tip > 5 cm below aortic arch or at T5-T6) or severely malpositioned (tip > 10 cm below aortic arch or at T7 or below).?Major complications were considered a composite of death secondary to IABP, major limb ischaemia, major IABP malfunction, balloon rupture or haemorrhage, severe renal dysfunction (rise in creatinine > 200 µmol/l), stroke and mesenteric ischaemia. Six hundred and forty-five cases were reviewed. The overall major complication rate was 26.2% and 24.3%. Severe renal impairment was the most common complication (16.6%), and second, severe catheter dysfunction (5.4%). ?Final IABP position was acceptable in 39.9%, malpositioned in 11.1%,?severely malpositioned in 6.7% and unavailable for 42.4%. Logistic regression analysis showed IABP tip malposition (compared with satisfactory position odds ratio=3.9 [95% confidence interval=2.0-7.6, P < 0.001] and severely malpositioned odds ratio=13.0 [95% confidence interval 5.3-31.7, P < 0.001]) was associated with major complications more than the presence of shock (odds ratio=3.8, confidence interval=2.1-6.8 P < 0.001). The acceptance of a less-than-ideal final position was highly predictive of morbidity directly related to IABP device therapy.

Immunization of mice with Plasmodium TCTP delays establishment of Plasmodium infection.

Translationally controlled tumour protein (TCTP) may play an important role in the establishment or maintenance of parasitemia in a malarial infection. In this study, the potential of TCTP as a malaria vaccine was investigated in two trials. In the initial vaccine trial, Plasmodium falciparum TCTP (PfTCTP) was expressed in Saccharomyces cerevisiae and used to immunize BALB/c mice. Following challenge with Plasmodium yoelii YM, parasitemia was significantly reduced during the early stages of infection. In the second vaccine trial, the TCTP from P. yoelii and P. berghei was expressed in Escherichia coli and used in several mouse malaria models. A significant reduction in parasitemia in the early stages of infection was observed in BALB/c mice challenged with P. yoelii YM. A significantly reduced parasitemia at each day leading up to a delayed and reduced peak parasitemia was also observed in BALB/c mice challenged with the nonlethal Plasmodium chabaudi (P.c.) chabaudi AS. These results suggest that TCTP has an important role for parasite establishment and may be important for pathogenesis.

Hypoxia-excited neurons in NTS send axonal projections to Kölliker-Fuse/parabrachial complex in dorsolateral pons.

Hypoxic respiratory and cardiovascular responses in mammals are mediated by peripheral chemoreceptor afferents which are relayed centrally via the solitary tract nucleus (NTS) in dorsomedial medulla to other cardiorespiratory-related brainstem regions such as ventrolateral medulla (VLM). Here, we test the hypothesis that peripheral chemoafferents could also be relayed directly to the Kölliker-Fuse/parabrachial complex in dorsolateral pons, an area traditionally thought to subserve pneumotaxic and cardiovascular regulation. Experiments were performed on adult Sprague-Dawley rats. Brainstem neurons with axons projecting to the dorsolateral pons were retrogradely labeled by microinjection with choleras toxin subunit B (CTB). Neurons involved in peripheral chemoreflex were identified by hypoxia-induced c-Fos expression. We found that double-labeled neurons (i.e. immunopositive to both CTB and c-Fos) were localized mostly in the commissural and medial subnuclei of NTS and to a lesser extent in the ventrolateral NTS subnucleus, VLM and ventrolateral pontine A5 region. Extracellular recordings from the commissural and medial NTS subnuclei revealed that some hypoxia-excited NTS neurons could be antidromically activated by electrical stimulations at the dorsolateral pons. These findings demonstrate that hypoxia-activated afferent inputs are relayed to the Kölliker-Fuse/parabrachial complex directly via the commissural and medial NTS and indirectly via the ventrolateral NTS subnucleus, VLM and A5 region. These pontine-projecting peripheral chemoafferent inputs may play an important role in the modulation of cardiorespiratory regulation by dorsolateral pons.

Methyl-CpG-binding protein 2 is localized in the postsynaptic compartment: an immunochemical study of subcellular fractions.

Methyl-CpG-binding protein 2 is a characteristic member of the methyl-CpG-binding protein family of transcription regulators. In conjunction with Sin3, MeCP2 recruits class I histone deacetylases to methyl-CpG regions to suppress transcription. Rett syndrome, a disorder characterized by mental retardation and autistic features, is associated in a majority of cases with mutations within the coding region of the MeCP2 gene. Considering that defective MeCP2 has mainly been related to Rett syndrome and other neurologic manifestations, we examined methyl-CpG-binding protein 2 cellular and subcellular compartmentalization in normal brain by immunochemical methods. Methyl-CpG-binding protein 2 immunoreactivity is present mainly in neurons; while the few immunostained glia show label confined to nuclei, many neurons also show slight perikaryal staining. Using well-characterized tissue fractions, we found that methyl-CpG-binding protein 2 but not Sin3 is found in both nuclear and postsynaptic compartments. This novel extranuclear localization is not unique to methyl-CpG-binding protein 2, since it has been previously reported for other transcription regulators such as c-Fos. These findings support the concept that methyl-CpG-binding protein 2 may link synaptic activity and transcriptional regulation in neurons.

Src homology 2 domain-containing inositol 5' phosphatase is negatively associated with histamine release to human recombinant histamine-releasing factor in human basophils.

BACKGROUND: The human recombinant histamine-releasing factor (HrHRF) acts as a complete stimulus for histamine release and IL-4 secretion from a subpopulation of highly allergic donor basophils, termed IgE(+) basophils. Additionally, IgE(+) basophils release histamine to other secretogues, IL-3, and deuterium oxide. We hypothesized that IgE(+) basophils were hyperreleasable. OBJECTIVE: Deficiencies in early signal transduction events associated with Fc(epsilon)RI lead to a nonreleasable phenotype, whereas the Src homology 2 domain--containing inositol 5' phosphatase (SHIP) knockout mice have hyperreleasable mast cells. The purpose of this study was to ascertain whether a difference in intracellular signaling molecules could explain the hyperreleasable phenotype of human IgE(+) basophils. METHODS: Basophils were purified by means of double Percoll gradients and negative selection with magnetic beads. Cell lysates were Western blotted for the tyrosine kinases Lyn and Syk and the phosphatase SHIP. Additionally, histamine release to HrHRF was performed in addition to real-time RT-PCR to investigate mRNA for SHIP. RESULTS: We show a striking negative correlation between the amount of SHIP protein per cell equivalent, but not Lyn or Syk, and maximum histamine release to HrHRF. This deficiency of SHIP was observed in basophils, but not lymphocytes or monocytes, of these IgE(+) donors. Additionally, levels of mRNA for SHIP did not differ between IgE(+) and IgE(-) donor basophils, which is consistent with a posttranscriptional mechanism of protein regulation. SHIP and phosphatidylinositol 3-kinase reciprocally regulate phosphatidylinositol (3,4,5) triphosphate levels. We also demonstrated that Ly294002, the phosphatidylinositol 3 kinase inhibitor, prevented HrHRF-induced histamine release in IgE(+) donor basophils. CONCLUSION: Taken together, these data suggest that the hyperreleasability of IgE(+) donors is associated with low levels of SHIP and implicate SHIP as an additional regulator of secretion in human basophils.

Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo.

The Plasmodium falciparum translationally controlled tumor protein (TCTP) is a homolog of the mammalian histamine-releasing factor (HRF), which causes histamine release from human basophils and IL-8 secretion from eosinophils. Histamine, IL-8, and eosinophils have been reported to be elevated in patients with malaria. This study was undertaken to determine whether malarial TCTP is found in the plasma of malaria-infected patients and to determine whether it has HRF biologic activity. Malarial TCTP was found in lightly infected human volunteers and in heavily infected Malawian children, but not in uninfected patients. Recombinant malarial TCTP, like HRF, stimulated histamine release from basophils and IL-8 secretion from eosinophils in vitro. Whereas malarial TCTP was less active than HRF, the concentrations that were effective in vitro could be achievable in vivo. These data suggest that malarial TCTP, present in human plasma during a malarial illness, may affect host immune responses in vivo.

Actinic prurigo: clinical features and HLA associations in a Canadian Inuit population.

BACKGROUND: Actinic prurigo (AP) is an idiopathic familial photodermatitis. AP of the Inuit is rarely reported and poorly characterized. OBJECTIVE: Our purpose was to examine the clinical features and HLA associations of AP in an Inuit population. METHODS: Thirty-seven Inuit subjects with AP were administered a questionnaire and underwent a cutaneous examination. Other causes of photosensitivity were excluded. HLA class I typing was performed by polymerase chain reaction and sequence-specific primers and class II typing by polymerase chain reaction and sequence-specific oligonucleotide probes. RESULTS: Subjects were 81.1% female, 67.6% had a family history of photosensitivity, and all experienced seasonal variation. The average age at onset of photosensitivity was 29 years, and only 27% had a trend toward improvement in photosensitivity. Involvement of eyes and nonexposed skin was reported in 62.2% and 18.9% of subjects, respectively. Physical examination revealed involvement of the face (64.9%), lip (32.4%), ear (13.5%), and dorsal aspect of the hand (24.3%). HLA-DRB1*14 was present in 51.2% of subjects and 26.2% of controls (P =.022, odds ratio = 2.975). This is a previously unreported HLA association. CONCLUSION: AP in the Inuit is a seasonal, pruritic photodermatitis, often commencing in adulthood and worsening over time. A novel association with HLA-DRB1*14 has been discovered. Overall, this novel HLA association, the absence of HLA associations previously reported in non-Inuit populations, and clinical distinguishing features support the concept that AP in the Inuit may have a distinct immunopathogenic basis that translates into a different phenotype. It also raises the question of whether AP in the Inuit is a distinct photosensitivity disorder specific to this group that has been genetically isolated because of geographic and cultural seclusion.

Human recombinant histamine-releasing factor activates human eosinophils and the eosinophilic cell line, AML14-3D10.

The human recombinant histamine-releasing factor (HrHRF) was previously shown to induce histamine release from human basophils from a subset of donors. The ability of HrHRF to directly induce histamine release from only certain basophils was thought to involve interaction between HrHRF and a particular kind of IgE, termed IgE(+), on the surface of these cells. Recent studies disproved the hypothesis that the IgE molecule or its high-affinity receptor, FcepsilonRI, is involved in secretion of histamine and cytokines by basophils stimulated with HrHRF. Rather, data suggest that HrHRF is a cytokine that stimulates basophils by binding to a cell-surface structure other than the IgE molecule. This report describes the effects of HrHRF on another inflammatory cell type: eosinophils from mildly allergic donors. In purified eosinophils primed with granulocyte-macrophage colony-stimulating factor, both tumor necrosis factor alpha (TNF-alpha) and HrHRF induced increased secretion of interleukin (IL) 8. In addition, both HrHRF and IL-5 enhanced secretion of IL-8 stimulated by TNF-alpha. Secretion of IL-8 reached a plateau level in less than 24 hours, was inhibited by cycloheximide, and required the presence of HrHRF throughout the culture period. In some eosinophil preparations, HrHRF induced calcium mobilization that was inhibited by pertussis toxin. Additionally, HrHRF caused secretion of IL-8 from the human eosinophilic cell line, AML14-3D10, which does not possess the alpha chain of FcepsilonRI. These data provide evidence that HrHRF contributes to activation of eosinophils and thus suggest an additional role for HrHRF in the pathophysiologic mechanisms of allergic disease.

Dendritic cytoskeletal protein expression in mental retardation: an immunohistochemical study of the neocortex in Rett syndrome.

Many syndromes associated with mental retardation (MR) are characterized by cortical dendritic anomalies. Despite their morphological similarity, these changes appear to involve different stages of dendritic development. The neuronal cytoskeleton, which includes microfilaments, neurofilaments and microtubules, is essential for these developmental processes. Levels and phosphorylation of microtubule-associated proteins (MAPs), which stabilize microtubules, seem to determine different stages of dendritic formation with certain MAPs (e.g. MAP-2) appearing to mediate the effects of external modulators upon these processes. Early studies on neuronal cytoskeleton in MR, which have shown a selective reduction in MAP-2 expression, have focused on Rett syndrome (RS). Here, by a semiquantitative immunohistochemical analysis of the pericentral cortex, we examine the contribution of specific neuronal populations to these changes in cytoskeletal proteins. Decreased MAP-2 staining in RS was more marked in layers V-VI, while increased nonphosphorylated neurofilament immunoreactivity was found in layers II-III in RS. Age-related increases in dendritic MAP-2 immunoreactivity in layers V-VI were also absent in RS. The specificity of these cytoskeletal protein changes, their significance for RS pathogenesis and plasticity, as well as their implications for other MR-associated disorders, are also discussed.

Pharmacologic regulation of histamine release by the human recombinant histamine-releasing factor.

BACKGROUND: The recently cloned human recombinant IgE-dependent histamine releasing factor (HrHRF) was initially thought to stimulate histamine release from human basophils from a subpopulation of allergic donors by interacting with the IgE molecules on the surface of these cells. Additional data suggest that HrHRF exerts its biologic effects by binding to a distinct cell surface structure and not to IgE. OBJECTIVE: To address the hypothesis that the HrHRF signaling pathway is distinct from the classical high-affinity IgE receptor (FcepsilonRI) pathway, we used pharmacologic agents known to affect basophil histamine release. METHODS: In this report we compared the effect of staurosporine, Bis II, Gö 6976, rottlerin, and pertussis toxin on histamine release from human basophils mediated by the following stimuli: HrHRF, polyclonal human anti-IgE antibody, and antigen, as well as the IgE-independent stimulus, FMLP. RESULTS: None of these modulators, except rottlerin, could differentiate histamine release induced by anti-IgE or antigen from that induced by HrHRF. Rottlerin enhanced HrHRF-mediated histamine release and dose dependently blocked FMLP-mediated release without affecting basophil activation by either anti-IgE or antigen. CONCLUSION: These data suggest a unique signaling pathway for HrHRF and thus strengthen the hypothesis that HrHRF binds to a specific receptor other than IgE.

The human recombinant histamine releasing factor: functional evidence that it does not bind to the IgE molecule.

BACKGROUND: We have previously shown that the human recombinant histamine releasing factor (HrHRF) caused histamine release from a subset of basophils from donors with allergy, and this release seemed to be dependent on the presence of a certain type of IgE, termed IgE+. IgE molecules that did not support HrHRF-induced histamine release were termed IgE-. However, subsequently we demonstrated that HrHRF primes anti-IgE-antibody-induced histamine release from all basophils, irrespective of the type of IgE on the cell surface. OBJECTIVE: Because these data suggested that HrHRF does not exert its biologic effects by binding to IgE, but rather that it interacted with a surface receptor on the basophil, we wanted to obtain functional evidence that HrHRF did or did not bind to the IgE molecule. METHODS: The rat basophilic leukemia cell line (RBL-SX38), which has been transfected to express a functional human FcepsilonRI (alpha-, beta-, and gamma-chains of the receptor) in addition to the normal rat FcepsilonRI, was used. The presence of the human FcepsilonRI receptor enables these cells to be sensitized with human IgE. Cells were passively sensitized with 1000 ng/mL human IgE+ or 1000 ng/mL human IgE- for 60 minutes at 37 degrees C. Unsensitized cells served as a control. After the cells were washed, 1 x l0(5) cells were stimulated in the presence of 1 mmol/L Ca2+ with 0.1 microg/mL anti-IgE, 40 microg/mL HrHRF, or 40 microg/mL mouse recombinant HRF (MrHRF), which has 96% homology to HrHRF. RESULTS: Mean anti-IgE-induced histamine release was 33% +/- 15%, and there was no difference between IgE+ sensitization (32% +/- 12%) and IgE- sensitization (34% +/- 18%). However, in contrast to human basophil experiments, neither HrHRF (0% +/- 0%) nor MrHRF (3% +/- 5%) caused histamine release in RBL cells sensitized with IgE+. In addition, priming the transfected RBL-SX38 cells or the parental cell line, RBL-2H3 cells, with HrHRF or MrHRF did not increase anti-IgE-induced histamine release. CONCLUSION: The results indicate that HrHRF does not bind to IgE, either IgE+ or IgE-. Therefore it appears likely that rHRF signals through its own specific receptor, which is not expressed or functional on RBL-SX38 or RBL-2H3 cells, but which seems to be expressed on basophils of atopic and nonatopic donors.

The management of ear disease: guidelines for Aboriginal health care programs.

Middle ear disease represents a continuing burden of illness for children of circumpolar regions. Uncertainty in management has been shown to create a barrier to timely and adequate treatment. Consistent intervention strategies were sought for the management of middle ear disease in children of the central Canadian Arctic. The current literature was reviewed using MEDLINE. A consensus document was established in consultation with specialists in community medicine, infectious disease, otolaryngology, pediatrics, and community-based care providers. Definitive recommendations and supportive algorithms have been established for management of middle ear disease in Inuit children.

HrHRF: function and regulation.

Since basophils appear to play a fundamental role in the maintenance of allergic inflammation, the factors involved in basophil activation have become a focus of investigation in many laboratories. From this interest, the field of histamine-releasing factors (HRFs) has evolved. Our laboratory reported that a factor was present in late-phase skin blister fluids that caused basophil histamine release. It was hypothesized that basophil degranulation in these donors was mediated by the interaction of these HRFs with a certain kind of IgE, and upon experimentation a functional heterogeneity of the IgE molecule was uncovered. We designated the IgE from HRF responders as IgE+; the remaining IgE molecules designated were IgE-. Initially, it was thought that HrHRF might exert its activity by directly interacting with IgE+; however, a number of recent experiments have questioned this hypothesis. Observations suggest, in part, that HrHRF mediates biological activities on inflammatory cells by binding to a specific receptor rather than to the IgE molecule and/or the FcepsilonRI. In parallel with the search for an HrHRF receptor, a number of experiments have been performed to determine whether mediator release by this protein proceeds via a signal transduction pathway other than the one triggered by classic IgE-dependent stimuli such as anti-IgE antibody or antigen. Although further characterization is ongoing, the evidence thus far is consistent with the concept that HRF may be an important regulator of the cellular inflammation involved in the pathophysiology of allergy.

Regional and rural-urban differences in obesity in Canada. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To describe regional and rural-urban differences in weight and weight loss patterns in Canadian adults. DESIGN: Population-based, cross-sectional surveys. SETTING: Nine Canadian provinces (excluding Nova Scotia) from 1986 to 1992. PARTICIPANTS: A probability sample of 27,120 men and women aged 18 to 74 years was selected using the health insurance registration files in each province. Anthropometry was performed on 18,043 participants (67%). OUTCOME MEASURES: Region of Canada (Atlantic, central, western); rural or urban residence (rural if participant resided in a community whose population was < 10,000, urban if population > or = 10,000); body mass index (BMI, kg/m2); percentage of participants trying to lose weight; reasons for trying to lose weight; level of leisure-time physical activity. RESULTS: Overall, mean BMI values in rural men (26.1 kg/m2) and women (25.3 kg/m2) were not significantly different from urban counterparts (25.7 kg/m2 and 24.8 kg/m2, respectively). Similarly, obesity (BMI > or = 27 kg/m2) was as prevalent in rural men (37%) and women (30%) as in urban participants (34% and 28%, respectively). However, a difference was observed in western Canada where 41% of rural and 34% of urban men were obese (odds ratio [OR], adjusted for age and education = 1.29; 95% confidence interval [CI] 1.06, 1.57), as were 35% of rural and 25% of urban women (OR, adjusted for age and education = 1.47; 95% CI 1.17, 1.84). Among men in western Canada, the rural-urban differences were greatest in the 25-64 year age group, whereas in women the differences were present at all ages. Overall, in Canada, urban men (26%) are more likely than rural men (23%) to be trying to lose weight; the reverse was true for women (39% and 42%, respectively). CONCLUSION: Considerable regional and rural-urban differences are seen in the patterns of weight and weight loss in Canada. A fuller understanding of the underlying behavioural determinants of these differences is needed. On the basis of such an understanding, effective programs to promote healthy weights for individuals and communities in these areas might be developed.

Obesity in Canada: a descriptive analysis. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To describe the distribution of body fat, prevalence of obesity, and knowledge of cardiovascular disease in Canadian adults. DESIGN: Population-based, cross-sectional surveys. SETTING: Ten Canadian provinces between 1986 and 1992. PARTICIPANTS: A probability sample of 29,855 men and women aged 18 to 74 years was selected using health insurance registration files in each province. Anthropometry was performed on 19,841 (66%) of these adults. OUTCOME MEASURES: Body mass index (BMI); waist circumference; ratio of waist to hip circumference; knowledge of causes of heart disease. RESULTS: The overall prevalence of obesity (BMI > or = 27 kg/m2) increased with age and was greater in men (35%) than in women (27%). Abdominal obesity was also higher in men and increased with both age and BMI. Canadians with lower levels of education had a higher prevalence of obesity, which appeared at a young age. Canadians in Atlantic Canada mentioned lack of exercise, poor diet and smoking as causes of heart disease less frequently than those living in central or western Canada. CONCLUSIONS: Obesity continues to be common among Canadian adults. Policy and programs to promote healthy body weights must be intensified and directed at specific sociodemographic groups.

Recombinant histamine-releasing factor enhances IgE-dependent IL-4 and IL-13 secretion by human basophils.

Human recombinant histamine-releasing factor (HrHRF) is known to directly stimulate histamine release and IL-4 secretion from basophils of selected atopic donors in a reaction requiring the expression of a particular type of IgE, referred to as IgE+. In this study, HrHRF is shown to affect the IgE-mediated release of IL-4, IL-13, and histamine from basophils not normally releasing to this protein (i.e, those expressing IgE-). Priming with several different concentrations of HrHRF for 15 min enhanced basophil secretion of IL-4 and histamine after 4 h in a dose-dependent fashion following activation with anti-IgE Ab (10 ng/ml). This effect of HrHRF priming also occurred in cultures activated with 1 or 100 ng/ml of anti-IgE Ab. The secretion of IL-13 protein was enhanced similarly by HrHRF priming in cultures stimulated for 16 to 20 h with anti-IgE Ab. There were, however, no apparent changes in the secretion of histamine or cytokine by basophils primed with HrHRF and activated with the IgE-independent secretogogue, FMLP. These findings suggest that HrHRF modifies the response of basophils for IgE-dependent secretion by binding to a specific receptor, broadening the possible role of this protein in chronic allergic inflammation.

Self-determination in terminal care. A comparison of GP and community members' responses.

OBJECTIVES: To examine health practitioner and community concerns, priorities and preferred options regarding patient self-determination in terminal care. METHOD: A postal questionnaire was sent to 229 general practitioners in two areas of Queensland (Brisbane and Wide Bay) and to 1100 community members throughout Queensland. Questions covered a range of end of life decision making issues, including where people wish to die, the use of advance directives and proxy decision makers, and possible barriers to such options. RESULTS: GPs and community members held very different opinions on most issues: community members were divided between home, hospital and hospice as a preferred place to die, while GPs strongly favoured home as their preferred place to die. Both groups supported the use of advance directives and proxies, but differed significantly with respect to barriers preventing the use of such options. CONCLUSION: Clarifying differences in perceptions and preferred options between the two groups on end of life decision making should not only improve communication and interactions between GPs and their patients but also allow both groups to become full participants in current policy and practice debates on end of life decisions.

Regulation of IgE-dependent IL-4 generation by human basophils treated with glucocorticoids.

Glucocorticoids are widely used in the therapeutic intervention of allergic diseases, affecting the function of a variety of proinflammatory cell types that participate in these disorders. These drugs have been shown to inhibit the release of histamine by human basophils, but not by mast cells, in a reaction requiring 8 to 24 h. To address whether the generation of IL-4 by basophils is similarly affected, we investigated the actions of glucocorticoids on the in vitro release of this cytokine induced by anti-IgE Ab or by the human recombinant histamine-releasing factor. The ability of basophils to generate IL-4 was immediately affected, with secretion of this protein being inhibited >50% with <1-h preexposure to steroid. However, the release of histamine in these cultures was inhibited only after 24-h preincubation, suggesting that the mechanisms controlling the release of this mediator differ significantly from those regulating cytokine secretion. A rank order of potency of the steroids tested for inhibition of IL-4 protein was as follows: triamcinolone > dexamethasone > betamethasone > hydrocortisone. The sex steroids, testosterone and estrogen, showed no effect on basophil secretion. Experiments using reverse transcription-PCR indicate that glucocorticoids inhibit IL-4 generation in basophils on the level of transcription. These studies suggest that the success of glucocorticoids in the treatment of allergic conditions is due in part to their ability to inhibit both mediator release and cytokine secretion by basophils.