Tako-tsubo-like cardiomyopathy after EpiPen administration.

Tako-tsubo-like cardiomyopathy is characterized by acute chest pain, electrocardiographic changes and increased cardiac enzymes in the absence of obstructive coronary vessel disease. We describe the development of tako-tsubo-like cardiomyopathy in an elderly woman after the use of an EpiPen for generalized urticaria and angioedema. As adrenaline may participate in the pathogenesis of this condition, the need for careful patient selection and education in the use of adrenaline self-injectors remains imperative.

Particulate masks and non-powdered gloves reduce latex allergen inhaled by healthcare workers.

BACKGROUND: Although allergy to latex is a well-characterized phenomenon, some hospitals continue to provide staff with powdered latex gloves as an option to low- or non-powdered gloves. OBJECTIVE: We aimed to measure the extent to which inhalation of latex particles could be reduced by the use of protective masks or by replacing powdered latex gloves with non-powdered latex gloves. METHODS: Twenty healthcare workers in a hospital setting wore nasal air samplers (NAS) and Institute of Occupational Medicine (IOM) samplers for four 20-min periods. Subjects wore powdered gloves, non-powdered gloves and no gloves during three sampling periods, and in the fourth, subjects applied an aerosol barrier face-mask or a particulate face-mask (N95) while wearing powdered gloves. All samples were stained for particles bearing Hev b 5 allergen by the Halogen assay. RESULTS: All subjects inhaled Hev b 5 bearing particles in all sampling periods. IOM samplers collected particles at 70% of the rate of NAS. The number of particles inhaled while wearing powdered gloves was 23.8-fold higher than when not wearing gloves and 9.7-fold higher than when wearing non-powdered latex gloves (P < 0.0001). Wearing an aerosol barrier mask did not significantly reduce the number of particles inhaled (P = 0.108), while use of particulate masks significantly reduced the number of particles inhaled by 17.4-fold (P = 0.003). CONCLUSIONS: Use of non-powdered gloves is the most effective method of reducing occupational aeroallergen exposure to latex arising from gloves. However, secondary protection using particulate masks is a valid alternative, and may be helpful for preventing respiratory sensitization.

Latex allergy: towards immunotherapy for health care workers.

Latex allergy is an important allergic disease for which safe and readily available immunotherapy is currently lacking. Despite advances in latex glove technology and reduction in allergen content, there remains a core of severely allergic health care workers (HCW), particularly with concominant food allergy, for whom allergen avoidance is insufficient. Current experience with immunotherapy using crude latex extracts has shown an unacceptable level of local and systemic side-effects. Latex allergens are extremely potent with a heightened capacity to cross-link effector cell-bound IgE and induce anaphylaxis. The predominant pattern of allergen reactivity among HCW is different from that among children with spina bifida, perhaps due to exposure to latex glove proteins, particularly via inhalation, rather than particle bound latex proteins present in urinary catheters. Recent studies using purified skin testing reagents have indicated that the most clinically important latex allergens amongst HCW are Hev b 5, 6 and 7. Elucidation of the molecular and cellular mechanisms of the immune response to these allergens is pivotal to facilitate the search for safer immunotherapy of latex allergy among HCW.

Specific monoclonal antibodies and human immunoglobulin E show that Hev b 5 is an abundant allergen in high protein powdered latex gloves.

BACKGROUND: Hev b 5 is a major latex allergen recognized predominantly by latex-allergic health care workers (HCWs). Recombinant Hev b 5 (rHev b 5) was previously expressed as a fusion protein with maltose binding protein (MBP), itself an immunogenic molecule; therefore non-fusion rHev b 5 is desirable. Moreover, standardized immunological assays for the detection of Hev b 5 are currently lacking and may have important implications for both allergen avoidance and diagnosis in latex allergy. OBJECTIVES: To generate and use Hev b 5-specific mAbs to determine the relative abundance of Hev b 5 in different latex extracts, correlating this with the IgE reactivity of latex-allergic HCWs and to produce non-fusion rHev b 5. METHODS: For the production of mAbs, mice were immunized with rHev b 5/MBP fusion protein and mAbs selected with rHev b 5/MBP but not MBP reactivity. The mAb reactivity was compared with polyclonal IgE from latex-allergic HCWs using direct and inhibition ELISA and immunoblot assays. Recombinant Hev b 5 was expressed and purified in the pPROEX-HTa bacterial expression system. RESULTS: Four Hev b 5-specific mAbs were produced. Immunoblotting and ELISA using the mAbs indicate abundant Hev b 5 in high protein powdered latex glove extracts as compared with crude latex sap extracts. High quality surgical gloves with no detectable protein have no detectable Hev b 5. Inhibition ELISAs using serum IgE from latex-allergic HCWs and Hev b 5-specific mAbs gave strong correlation. Non-fusion recombinant Hev b 5 was successfully expressed and purified, showing reactivity with both the Hev b 5-specific mAbs and serum IgE of latex-allergic HCWs. CONCLUSION: Hev b 5-specific mAbs and human IgE from latex-allergic HCWs demonstrate the greater content of Hev b 5 in high protein powdered glove extracts. This may explain the observed higher frequency of sensitization to this allergen in HCWs.

Human T-cell epitopes of the latex allergen Hev b 5 in health care workers.

BACKGROUND: Latex allergy affects health care workers as a high-risk cohort. Hev b 5 is a major latex allergen reacting with serum IgE from 92% of latex-allergic health care workers. Because CD4(+) T-cell recognition is central to the specific immune response to allergens, identification of dominant T-cell epitopes is important for the development of specific immunotherapy for latex allergy. OBJECTIVE: Our purpose was to map T-cell epitopes of Hev b 5 in health care workers. METHODS: Six latex-allergic health care workers (grade 3 to 4 enzyme allergosorbent test score) were studied. Peripheral blood latex specific 3-week T-cell lines were generated and screened for proliferative response to overlapping 20-mer peptides of Hev b 5. Supernatants collected at 48 hours were analyzed by ELISA for IL-5 and IFN-gamma. RESULTS: Dot immunoblotting with use of recombinant Hev b 5/maltose-binding protein indicated serum-specific IgE in 5 of 6 patients. T-cell reactivity to one or more Hev b 5 peptides was identified in these 5 donors, but not in the sixth. Hev b 5 (46-65) induced T-cell proliferation in all 5 donors. Hev b 5 (109-128) stimulated T cells from 3 of these patients. Proliferative responses were accompanied by substantial IL-5 secretion and minimal IFN-gamma, indicating a T(H)2-predominant cytokine profile. CONCLUSIONS: Five of 6 latex-allergic patients demonstrated T-cell responsiveness to Hev b 5 consistent with a major T-cell reactive latex allergen. Two T-cell immunodominant regions of Hev b 5 were identified, and reactivity to these sites was associated with strong IL-5 but minimal IFN-gamma production.

Changes in the maternal and fetal renin-angiotensin systems in response to angiotensin II type 1 receptor blockade and angiotensin-converting enzyme inhibition in pregnant sheep during late gestation.

The effects of maternal administration of either an angiotensin II type 1 (AT1) receptor antagonist (GR138950) or an angiotensin-converting enzyme (ACE) inhibitor (captopril) on the renin-angiotensin system (RAS) were investigated in chronically catheterized ewes and their fetuses during late gestation. From 127 +/- 1 days of gestation until parturition at 145 +/- 2 days, each ewe received daily i.v. injections of GR138950 (3 mg kg-1, n = 10 animals) or captopril (3 mg kg-1, n = 6) or an equivalent volume of vehicle solution (0.9% NaCl, n = 10). On the first day of treatment, plasma renin concentrations in the pregnant ewe increased within 2 h of administration of either GR138950 (median change followed by lower and upper quartiles (25%, 75%): +38.3 ng ml-1 h-1 (15.6, 80.7); P < 0.05) or captopril (+22.1 ng ml-1 h-1 (19.2, 28.8); P < 0.05). Maternal plasma concentrations of angiotensin II (AII) also increased by 871 pg ml-1 (555, 1340; P < 0.05) in the GR138950-treated ewes. In the fetuses of both groups of drug-treated animals, an increase in plasma renin concentration was observed within 2 h of maternal treatment with either GR138950 (+11.6 ng ml-1 h-1 (1.2, 18.6); P < 0.05) or captopril (+59.3 ng ml-1 h-1 (41.7, 74.6); P < 0.05). These short-term changes in circulating renin and AII concentrations observed in the pregnant ewe were sustained after 1 week of GR138950 administration. In addition, 1 week of GR138950 treatment decreased plasma angiotensinogen (Ao) concentrations in both the ewe (-0.36 microgram ml-1 (-0.58, -0.16); P < 0.05) and the fetus (-0.43 microgram ml-1 (-0.59, -0.09); P < 0.05). A long-term reduction in maternal plasma AII, and an increase in fetal plasma renin concentration, were associated with 1 week of captopril administration. Neither drug had any consistent effect on plasma ACTH or cortisol concentrations in the pregnant ewe or fetus. These findings show that, during ovine pregnancy, antagonism of maternal AII activity, either by blockade of the AT1 receptor or by inhibition of AII synthesis, induces changes in the circulating components of the RAS in the mother and fetus. In both the pregnant ewe and fetus, the RAS is shown to be activated by suppression of AII activity.

Haemodynamic responses to an angiotensin II receptor antagonist (GR 117289) in maternal and fetal sheep.

An AT1-specific angiotensin II receptor antagonist (GR117289; 1 mg/kg I.V. bolus) was administered daily to ten chronically catheterized, normotensive ewes during late pregnancy (from 126 +/- 1 days) until parturition (139 +/- 1 days); five control animals received an equivalent volume of vehicle solution. Following drug administration, mean maternal blood pressure decreased from 87 +/- 1 mmHg to a minimum of 79 +/- 1 mmHg at 0.5 h (P < 0.05; n = 10) and remained low for 4-6 h without any concomitant change in fetal blood pressure or maternal and fetal heart rates. In animals fitted with flow probes, uterine blood flow decreased from 443 +/- 21 to 363 +/- 27 ml/min at 0.5 h post-drug (P < 0.05; n = 6); this change was positively correlated with the reduction in maternal blood pressure. The mean decrements in uterine and umbilical blood flows measured by steady-state infusion of tritiated water were -611 +/- 171 ml/min at 4-6 h (P < 0.05; n = 5) and -71 +/- 19 ml/min at 0.5-1 h (P < 0.05; n = 5), respectively. Significant reductions (P < 0.05; n = 10) in fetal arterial oxygen tension (-1.6 +/- 0.4 mmHg), saturation (-6.6 +/- 1.6%) and content (-0.3 +/- 0.1 mumol/ml) were evident at 0.5 h post-drug and were maintained for 6-12 h. Umbilical oxygen delivery decreased at 0.5-1 h following drug administration (P < 0.01; n = 5), but was unaccompanied by any significant change in fetal oxygen consumption. Chronic decreases in daily fetal pH and blood oxygen content occurred in GR117289-treated ewes. There were no significant differences in gestational length or neonatal outcome between vehicle- and GR117289-treated groups of ewes with single fetuses.

Teratogenicity of three substituted 4-biphenyls in the rat as a result of the chemical breakdown and possible metabolism of a thromboxane A2-receptor blocker.

AH23848 is a potent thromboxane A2-receptor blocker inhibiting platelet aggregation in vitro and in vivo. Oral administration to pregnant rats during days 7-16 of pregnancy, at doses of 0, 10, 45, or 200 mg/kg twice daily, resulted in dose-related maternal, embryonic, and fetal toxicity. The most notable observation was herniation of the diaphragm occurring in 1.5 and 100.0% of fetuses at the 45 and 200 mg/kg doses, respectively, when examined at term. A further study at 150 mg/kg twice daily during days 7-16, 7-11, or 12-16 of pregnancy revealed incidences of diaphragmatic hernia up to 42%. Herniation varied from small areas of eventration of membranous diaphragm to fetuses with apparent total absence of the diaphragm. The positions of the hernias in the diaphragm, following dosing over varying periods of organogenesis, reflected the chronology of diaphragm formation in the rat. The teratology of AH23848 was unrelated to its thromboxane A2-receptor blocker properties but was related to a chemical breakdown product, 4-biphenylmethanol. Some substituted biphenyl compounds appear to be specific teratogens in the rat, with their effects targeted at the developing diaphragm. A possible mechanism of herniation is the interference with muscularisation of the membranous diaphragm, resulting in weakness and perforation.