The Case of Pregnant Women with Bioprosthetic Valve Replacement Suggested by My Canadian Pharmacy

valve prosthesisPregnancy in women with mechanical valve prosthesis is dangerous mainly because of problems originating from oral anticoagulants. Warfarin derivatives, necessary for thromboembolism prevention and avoidance of maternal mortality, have a teratogenic and hemorrhagic effect upon the fetus reflected in a high fetal mortality. Avoidance of oral anticoagulants should result in a normal or nearly normal course of pregnancy in women with prosthetic cardiac valves.

Twenty female subjects with bioprosthetic valve replacement were treated with aspirin as the only antithrombotic drug. This is the largest series of pregnant women with bioprostheses reported in the literature.

Continue reading “The Case of Pregnant Women with Bioprosthetic Valve Replacement Suggested by My Canadian Pharmacy”

Regulatory T Cells in Allergy and Asthma: Targets for Intervention

Targets for InterventionBased on the studies reported here, it is clear that targeting of a number of cell-surface molecules and soluble mediators may be beneficial in asthma. DCs activated with TSLP are involved in the generation of Tr1s in the thymus, but Th2 cells in the periphery. Improved understanding of the signals that drive this divergent pathway may identify novel molecules as targets for intervention either alone, or in combination with TSLP. Signaling of tolerogenic DCs to naive T cells can lead to the development of IL-10-secreting Tr1-like regulatory cells. TGF-P is crucial in the development of CD4 + CD25+ Treg and induces expression of the master regulatory transcription factor Fox p3. While TGF-P has profibrotic characteristics that may compromise its use as a therapeutic, a combination of TGF-P and IL-10 may enhance regulatory function while reducing associated fibrosis. IL-6 is an archetypal proinflammatory cytokine that is able to enhance allergic airway disease and suppress the generation of Treg. Blockade of the IL-6 pathway has already been achieved in other clinical disorders and may prompt studies to evaluate this form of intervention in asthma.44 TSLP induces expression of the Th2 chemokines TARC and MDC, which drive recruitment of Th2 T cells to sites of allergic inflammation. Inhibitors of CC che-mokine receptor 4, the receptor for these molecules, are already being developed for the treatment of asthma.

Continue reading “Regulatory T Cells in Allergy and Asthma: Targets for Intervention”

Canadian Health&Care Mall Observes Defective Regulation in Allergic Diseases and Asthma

autoantigens Compromised regulation may provide an explanation for hyperreactivity to allergens and autoantigens. A number of studies have investigated the possibility that allergen-specific Treg function is defective in individuals with allergic diseases about which you may learn more on Canadian Health&Care Mall via (Fig 2). CD4+CD25+ T cells from grass pollen-allergic individuals were less able to suppress proliferative responses and IL-5 production by CD4+CD25-negative T cells. Moreover, suppression by CD4+CD25+ T cells was further compromised during the pollen season, suggesting that increased allergen dose in vivo may provide a strong enough stimulus to override Treg-mediated suppression.

Other similar studies have also found evidence of defective regulation but with some caveats. For example, CD4+CD25+ T-cell function from birch pollen-allergic subjects and nonallergic control subjects was compared in and out of season. While both groups had equivalent suppression of allergen-induced proliferation and similar suppression of IFN-7, suppression of Th2 responses appeared to be compromised in allergic subjects, as both CD4+CD25+ and CD4+CD25-negative T cells made IL-5 and IL-13 to birch pollen. The findings are consistent with the observation40 that Th2 thymocyte clones were more resistant to regulation by either CD4+CD25+ or CD8+CD25+ regulatory human thymocytes than were Th1 thymocyte clones.

Continue reading “Canadian Health&Care Mall Observes Defective Regulation in Allergic Diseases and Asthma”

Regulatory T Cells in Allergy and Asthma: Allergen-Specific Responses in Nonallergic Individuals

airway hyperresponsivenessCytokine production by allergen-specific T cells is crucial in establishing and maintaining the tolerant or inflammatory context of allergen recognition, Production of Th2 cytokines is associated with allergic diseases including asthma. The nonallergic phenotype has historically been associated either with a failure to recognize the allergen (immunologic ignorance) or the expression of a “protective” Th1 cytokine profile. Indeed, Th1 cytokine profiles have been reported in nonallergic individuals in response to allergen. However, Th1 responses to allergens would be expected to give rise to inflammatory responses such as delayed-type hypersensitivity reactions, which is not generally the case. Thus, allergic individuals respond to allergen with an inflammatory Th2 response, whereas nonallergic individuals appear to make an immune response that is associated with Th1 cytokines but is noninflammatory.

Studies suggest that active regulation is an essential element in maintaining noninflammatory peripheral tolerance to allergens in healthy individuals. Blood T cells were stimulated with aeroallergens and/or food allergens and subsequently selected on the basis of allergen-induced cytokine production. The profile of allergen-specific interferon (IFN)-^ (Th1 marker), IL-4 (Th2 marker), and IL-10 (antiinflammatory cytokine and marker [Tr1] of a population of regulatory T cells [Treg]) production differed between allergic and nonallergic subjects, with the ratio of cell numbers secreting these three cytokines determining the development of a healthy or allergic immune response. Thus, lowTr1 numbers and high Th2 cell numbers resulted in an allergic response, whereas in nonallergic individuals a mixed Th1/Th2 response was associated with a strong IL-10 response.14 Similarly, T-cell clones derived from children persistently allergic to cow milk produced Th2 cytokines (IL-4, IL-13), whereas allergic control subjects without cow milk allergy (but allergic to another food) produced a mixed Th1/Th2 response associated with markedly elevated IL-10 levels. Continue reading “Regulatory T Cells in Allergy and Asthma: Allergen-Specific Responses in Nonallergic Individuals”

Disscusion of Myocardial Dysfunction and Hemolytic Anemia in a Patient with Mycoplasma pneumoniae Infection

Myocardial involvementMyocardial involvement associated with infection with Mycoplasma pneumoniae was first reported by Rosner and associates, who described an 18-year-old patient who developed complete atrioventricular block during an upper-respiratory-tract illness. This patient had a change in the complement-fixation test consistent with recent infection with Mycoplasma, but levels of cold agglutinins and serum cardiac enzymes were normal. In a series of 18 patients with asymptomatic myocarditis associated with viral-like illnesses reported by Lewis et al, two patients had serologically proven infection with Mycoplasma. The myocarditis in these two patients was manifested only by abnormalities of the ST-T wave on the ECG and occurred concurrently with respiratory symptoms.

The cold-agglutinin hemolytic anemia associated with infections with Mycoplasma pneumoniae characteristically occurs in the second and third weeks of the illness, with the appearance of cold agglutinins in significant titers (> 1:512). The cold agglutinins are IgM antibodies with anti-I erythrocyte antigen specificity and have a high thermal maximum in those patients who develop hemolytic anemia. El Khatib and Lemer recently reported serologically proven infection with Mycoplasma in a patient with asymptomatic myoperi-carditis and hemolytic anemia associated with a markedly elevated titer of cold agglutinins. Of significant note is the fact that the myocarditis and hemolytic anemia occurred simultaneously on the 22nd day of illness, after resolution of an acute pneumonitis. At no time was the patients anemia severe enough to warrant transfusion. Continue reading “Disscusion of Myocardial Dysfunction and Hemolytic Anemia in a Patient with Mycoplasma pneumoniae Infection”

Myocardial Dysfunction and Hemolytic Anemia in a Patient with Mycoplasma pneumoniae Infection

Mycoplasma pneumoniaeMycoplasma pneumoniae is a common respiratory pathogen that may be associated with a variety of other complications, including erythema multiforme, meningitis, peripheral neuropathy, and hemolytic anemia. Myocarditis has also been previously described in association with infection with this organism, but the manifestations have been minor, both in the electrocardiographic change (nonspecific abnormalities of the ST-T wave) and in signs of cardiac dysfunction. In this communication, we present a patient who developed signs and symptoms of myocarditis during the course of infection withMycoplasma pneumoniae associated with severe hemolytic anemia.

Case Report

A 49-year-old white woman was hospitalized for evaluation of increasing shortness of breath, a cough productive of moderate amounts of yellowish-brown sputum, and fever of four days’ duration. There was no prior history of cardiac disease. Continue reading “Myocardial Dysfunction and Hemolytic Anemia in a Patient with Mycoplasma pneumoniae Infection”

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