Adverse reactions associated with echinacea: the Australian experience.

BACKGROUND: Fifty percent of Australians use complementary and alternative medicines (other than vitamins) in any 12-month period, of which echinacea-containing products are increasingly popular. Recent reports have highlighted the risk of allergic reactions to complementary medicines in atopic patients. OBJECTIVE: To determine the characteristics of adverse reactions linked to use of the popular herbal remedy echinacea. METHODS: Five privately referred patients were evaluated by the authors in their office practice via skin prick testing (SPT) on the volar aspect of the forearm and radioallergosorbent test after adverse reactions to echinacea. As there was little published information on adverse reactions to echinacea, reports to the Australian Adverse Drug Reactions Advisory Committee were reviewed. Those suggestive of possible allergic reactions were evaluated in greater detail by anonymously surveying the healthcare professionals who had reported the cases and from one unreported case. Serum was collected for further analysis where possible. RESULTS: Five cases of adverse reactions to echinacea were personally evaluated by the authors. Two patients suffered anaphylaxis and a third had an acute asthma attack 10 minutes after their first ever dose of echinacea. The fourth patient suffered recurrent episodes of mild asthma each time echinacea was ingested, and the fifth developed a maculopapular rash within 2 days of ingestion which recurred when rechallenged. Three of the patients had positive SPT results. Three reported repeated spontaneous "challenges" and symptoms after further ingestion of echinacea. Fifty-one Australian adverse drug reports implicating echinacea were also reviewed. There were 26 cases suggestive of possible immunoglobulin E-mediated hypersensitivity (4 anaphylaxis, 12 acute asthma, 10 urticaria/angioedema). Of these 26 patients, age ranged from 2 to 58 years, 78% were female and >50% were known to be atopic. Four were hospitalized, 4 reacted after their first known exposure, and 1 patient suffered multiple progressive systemic reactions. Twenty percent of 100 atopic subjects who had never taken echinacea also had positive SPT results to this substance when tested by one of the authors in his office practice. CONCLUSION: Some atopic subjects have positive SPT results to echinacea in the absence of known exposure. Atopic subjects are also overrepresented in those experiencing reactions to echinacea. The possibility that cross-reactivity between echinacea and other environmental allergens may trigger allergic reactions in "echinacea-na?ve" subjects is supported by the Australian data. Given its widespread (and largely unsupervised) community use, even rare adverse events become inevitable. Atopic patients should be cautioned appropriately.     

Adverse reactions to nitrofurantoin in relation to cellular and humoral immune responses.

Eighteen patients showing hypersensitivity to nitrofurantoin with symptoms like sudden fever, malaise, cough, pleuritis, leucocytosis and sometimes eosinophilia were analysed for immune reactions, i.e. lymphocyte transformation and specific antibodies. In addition, thirty-three individuals treated with the drug but with no clinical signs of the described reactions were included as controls. The lymphocyte transformation test (LTT) was found positive in ten out of the eighteen sensitive patients while one to three out of fourteen tested control patients were positive, depending on test conditions. An incubation period of 4 days in culture medium supplemented with autologous serum gave stimulation to a greater extent than did isologous serum and/or incubation for 6 days. The antibody determinations, with the enzyme-linked immunosorbent assay (ELISA), showed no IgE antibodies to nitrofurantoin in any of the patients. In contrast, most of the hypersensitive and even the control patients had specific IgG antibodies. The mean value of the antibodies of the sensitive group was higher than of the control group, but considerable overlapping between the groups was noted. In adverse reactions to nitrofurantoin a positive LTT and/or a high antibody titre to the drug favours an allergic mechanism and contributes to a more reliable diagnosis.     

Adverse reactions to foods.

Allergic reactions to foods represent a prominent, actual and increasing problem in clinical medicine. Symptoms of food allergy comprise skin reactions (urticaria, angioedema, eczema) respiratory (bronchoconstriction, rhinitis), gastrointestinal (cramping, diarrhea) and cardiovascular symptoms with the maximal manifestation of anaphylactic shock. They can be elicited by minute amounts of allergens. The diagnosis of food allergy is done by history, skin test, in vitro allergy diagnosis and--if necessary--oral provocation tests, if possible placebo-controlled. Avoidance of respective allergens for the allergic patient, however, is often complicated or impossible due to deficits in declaration regulations in many countries. Increasing numbers of cases including fatalities, due to inadvertent intake of food allergens are reported. It is therefore necessary to improve declaration laws and develop methods for allergen detection in foods. Allergens can be detected by serological methods (enzyme immunoassays, in vitro basophil histamine release or in vivo skin test procedures in sensitized individuals). The problem of diagnosis of food allergy is further complicated by cross-reactivity between allergens in foods and aeroallergens (pollen, animal epithelia, latex etc.). Elicitors of pseudo-allergic reactions with similar clinical symptomatology comprise low-molecular-mass chemicals (preservatives, colorings, flavor substances etc.). For some of them (e.g. sulfites) detection assays are available. In some patients classic allergic contact eczema can be elicited systemically after oral intake of low-molecular-mass contact allergens such as nickel sulfate or flavorings such as vanillin in foods. The role of xenobiotic components in foods (e.g. pesticides) is not known at the moment. In order to improve the situation of the food allergic patient, research programs to elucidate the pathophysiology and improve allergen detection strategies have to be implemented together with reinforced declaration regulations on a quantitative basis.     

Human immunodeficiency virus-1 specific and natural cellular immunity in HIV seronegative subjects with multiple sexual exposures to virus.

The probability of HIV infection by sexual contact, although it varies greatly, appears to be lower than that of infection by other routes of exposure. The aim of this study was to evaluate immunological determinants involved in protection against HIV infection in subjects with multiple and repeated sexual exposures to the virus. Twenty-two subjects were studied for CD8+ cell anti-HIV suppression activity and serum neutralizing activity against the HIV strain of their own partners, beta-chemokine production, and natural killer cell activity. CD8+ cell anti-HIV activity and neutralizing activity of sera were found in 13 (76%) and 12 (70.5%) out of 17 HIV-1 negative subjects, respectively. Six individuals had a relevant immune response against HIV: three subjects with a high CD8+ cell antiviral suppression activity and three individuals with sera neutralizing activity titer >1:10. These last three subjects had the highest beta-chemokine levels, a very prolonged period of multiple sexual intercourse (>6 years) and a seropositive partner with a high viral load. A partial reduction of neutralizing activity titer was observed when pre-incubating the sera with anti-beta-chemokine neutralizing antibodies. A spontaneous natural killer cell activity was suppressed in the majority of HIV-1 negative subjects with sexual exposure in comparison with normal individuals. The protection from sexual HIV transmission appears to be the result of a network of different humoral and cellular factors.     

Reciprocal antagonism between ACTH1-24 and beta-endorphin in rats

ACTH1-24 and beta-endorphin simultaneously injected at 5-10 microgram dose into the lateral ventricle, reciprocally suppress most of their respective behavioural effects (stretching-yawning syndrome, sexual excitement and hyperalgesia for ACTH1-24 and catalepsy and analgesia for beta-endorphin). The results obtained support the hypothesis that ACTH1-24 and beta-endorphin might interact antagonistically at CNS level.     

ACTH(1-24)的应用研究进展

失血性休克是临床上最常见的休克类型。促肾上腺皮质激素(adrenocorticotrphin,ACTH)的N端24肽[ACTH(1-24)]通过迷走神经抗炎通路的激活能快速、高效地发挥抗休克作用,并能降低休克的炎性连锁反应及显著减轻休克后器官的损伤和功能障碍,这将为新型药物的开发和急性失血性休克的治疗开辟新的领域。     

Adverse reactions to food additives.

OBJECTIVES: To summarize the literature related to the classification of food additives and their reported adverse reactions and to provide a practical approach for evaluation of patients suspected of having such reactions. DATA SOURCES: Information was derived from selected reviews and original articles published in peer-reviewed journals and from authoritative textbook chapters, supplemented by the clinical experience of the authors. STUDY SELECTION: Priority was given to studies that used blinded, placebo-controlled oral challenges to confirm adverse reactions to food additives. In addition, selected, appropriately evaluated case reports are included. RESULTS: A large number of food additives are widely used in the food industry. Adverse reactions to additives seem to be rare but are likely underdiagnosed in part due to a low index of suspicion. Numerous symptoms have been attributed to food additive exposure, but the cause-and-effect relationship has not been well demonstrated in all. CONCLUSIONS: Reactions to food additives should be suspected in patients who report symptoms to multiple unrelated foods or to a certain food when commercially prepared but not when homemade and the allergy evaluation rules out a role for food protein. It is also prudent to investigate food additives in patients considered to have idiopathic reactions. There is a minor role for skin testing or in vitro testing. Oral challenge testing with common additives, preferably preceded by a trial of an additive-free diet, is the definitive procedure for detecting the offending agent. Once the specific additive is identified, management is basically avoidance of all its forms.     

Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens

The aim of the study was to investigate whether adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ^® Phleum, ALK‐Abelló) are related to the different patterns of sensitization of patients to grass allergens. A total of 192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4‐week updosing with five injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association between the number of grass allergens that sensitized the patients and the total number of ADRs (P = 0.004) occurred locally (P = 0.003) and systemically (P = 0.01). Sensitization to Phl p1 + Phl p5 or Phl p1 + Phl p5 + Phl p12 was significantly associated with a higher frequency of local or systemic reactions (P = 0.001, both). Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy.     

Adverse cutaneous reactions due to macrolides.

Macrolides, which are widely prescribed and seldom produce hypersensitivity reactions, are considered to be safe drugs. We present five patients with generalized skin reactions due to erythromycin and/or spiramycin, proved by oral challenge tests. One patient showed reactions to both erythromycin and spiramycin. All skin prick and patch tests and histamine release tests with both macrolides were negative.     

Role of specific cytotoxic lymphocytes in cellular immunity against murine cytomegalovirus.

Cytotoxic lymphocytes were generated in vitro against murine cytomegalovirus (MCMV)-infected cells by incubation with ultraviolet light-irradiated, infected fibroblasts. When passively transferred, they reduced virus titers in spleens of mice 1 day after infection with MCMV. Protection was abrogated by anti-theta serum and complement. Spleen cells from mice infected for 6 to 14 days protected mice better than cells from mice after infection for 1, 3, or 30 days. Protection by in vitro- and in vivo-generated cells was H-2K or H-2D restricted. Specific cytotoxic T lymphocytes are therefore present and operative during acute MCMV infection. However, MCMV infection inhibited the development of primary cytotoxic response against ectromelia virus. It also suppressed the ability of lymphocytes from mice with established memory for ectromelia to develop secondary cytotoxic cells in vitro, and it inhibited the development of memory cells for the cytotoxic response to ectromelia virus. In view of these data and the inability of animals recovering from MCMV infection to eliminate all infected cells, the cytotoxic response to MCMV may be qualitatively or quantitatively deficient.     

Effects of acute central and peripheral ACTH1-24 administration on lordosis behavior

The role of adrenocorticotropic hormone (ACTH) in the control of the lordosis reflex of female rats was investigated. Experiment 1 examined the effects of ACTH^1–24 infused into the ventricular system of the brain. ACTH treatment lowered the performance of both ovariectomized (ovx) and adrenalectomized-ovariectomized (adx-ovx) extrogen-primed females. ACTH-treated females also showed evidence of spontaneous stretching, yawning, and grooming. Experiment 2 examined the effects of ACTH^1–24 administered subcutaneously. Here ACTH elevated performance of ovx but not adx-ovx estrogen-primed females. There was no evidence of spontaneous stretching, yawning, and grooming movements in females given peripheral ACTH. In both experiments, untreated adx-ovx females showed a higher level of lordosis than untreated ovx females. These results suggest that the central effect of acute ACTH elevation differs from the peripheral effect, and that the peripheral effect is probably mediated by the adrenal.     

Transfer of specific immunity with RNA.

The term "immune RNA" (iRNA), as presently used, refers not to a characterized species of RNA but to phenol extracts of lymphocytes from immunized animals, which have the capacity to transfer a variety of immune products or activities. These include synthesis of specific antibody, development of specific cellular (delayed) hypersensitivity, and production of immunoglobulin allotypic or idiotypic specificities. Recent evidence that iRNA might be used as a specific therapeutic agent to induce immunity to tumors has stimulated an increased interest in this area of research. The purpose of this article is to review the current status of studies on iRNA.     

乙型肝炎患者特异性细胞免疫功能检测的初步研究

目的 通过酶联免疫斑点法检测乙型肝炎（乙肝）患者特异性细胞免疫功能，初步研究各型乙肝患者特异性细胞免疫功能的差异。方法 选择急、慢性乙肝、肝炎肝硬化（乙型）、乙肝病毒（HBV）既往感染，接种乙肝疫苗后血清乙肝病毒学标志中仅表面抗体阳性及未接种过乙肝疫苗、未感染过HBV、血清HBV标志全部阴性者共6组研究对象，每组4例，采用酶联免疫斑点法（ELISPOT）检测其外周血单个核细胞中γ-干扰索分泌细胞的数量。结果 急性乙肝患者、慢性乙肝患者及急性乙肝患者、肝炎肝硬化患者外周血单个核细胞γ-干扰素分泌细胞数量明显不同（P=0．0209及P=0．0211）。结论 通过ELISPOT检测乙肝患者外周血单个核细胞γ-干扰索分泌细胞的数量可以了解乙肝患者特异性细胞免疫功能。急性乙肝患者特异性细胞免疫功能明显强于慢性乙肝患者及肝炎肝硬化患者。