Hymenoptera venom allergy: time course of specific IgE concentrations during the first weeks after a sting.

Detection of IgE antibodies specific to honeybee or Vespula venoms is an important criterium firstly for the diagnosis of sensitization and secondly for the indication for a specific immunotherapy. Some authors recommend to postpone blood analysis after an insect sting for a certain time because circulating IgE antibodies might be consumed by the allergic reaction, which would result in a false-negative test outcome. We investigated IgE concentrations during the first weeks after an insect sting in 31 patients with an unequivocal history of an anaphylactic reaction after a honeybee (n = 13) or Vespula (n = 18) sting. Blood samples for analysis of specific IgE concentrations (CAP system, Pharmacia Diagnostics, Sweden) were collected within 2 weeks and 5+/-2 weeks after the insect sting. 12/13 patients with honeybee venom and 14/18 patients with Vespula venom sensitization had CAP classes 1 or higher within the first 2 weeks. Those 5 patients with CAP class 0 within the first 2 weeks had detectable IgE concentrations a few weeks later. We conclude that testing for specific IgE to hymenoptera venoms is in most cases useful even during the first 2 weeks after the hymenoptera sting. This allows early decisions on further diagnostic procedures and the therapeutic way to choose. Patients with no detectable IgE should, however, be retested after a few weeks.     

Fatal anaphylactic sting reaction in a patient with mastocytosis

We report on a 33-year-old female patient with indolent systemic mastocytosis and urticaria pigmentosa who died of an anaphylactic reaction after a yellow jacket sting. As she had no history of previous anaphylactic sting reaction, there was no testing performed in order to detect hymenoptera venom sensitization. But even if a sensitization had been diagnosed, no venom immunotherapy (VIT) would have been recommended. It is almost certain that VIT would have saved her life and it is most likely that VIT is indicated in some patients with mastocytosis with no history of anaphylactic sting reaction. However, no criteria have been established in order to allow a selection of mastocytosis patients eligible for such a 'prophylactic' VIT.     

Discontinuation of yellow jacket venom immunotherapy: Follow-up of 75 patients by means of deliberate sting challenge

Background: Venom immunotherapy is effective in preventing systemic reactions in patients with a history of an anaphylactic reaction to Hymenoptera stings. It is uncertain how long venom immunotherapy should be continued. Objective: We evaluated whether the duration of venom immunotherapy given to yellow jacket–sensitive patients related to the risk of an anaphylactic reaction to a later sting. Methods: Seventy-five yellow jacket–sensitive patients (29 male and 46 female) received a median number of three in-hospital sting challenges from a live insect in 3 subsequent years after discontinuation of venom immunotherapy. An anaphylactic reaction to one or more of the sting challenges was considered a relapse. We analyzed whether patients with and patients without a relapse differed in terms of gender, age, preimmunotherapy skin test data, preimmunotherapy level of venom-specific IgE, severity of the field-sting reaction that preceded immunotherapy, severity of the reaction to the sting challenge that preceded immunotherapy, adverse reactions to immunotherapy, changes in IgE and IgG₄ levels during immunotherapy, duration of immunotherapy, and presence of venom-specific IgE after cessation of therapy. Results: Venom immunotherapy was given for a median duration of 40 months (range, 7 to 120 months). Relapses were observed in six patients. In two of them, a rather severe anaphylactic reaction was observed after the second sting challenge. No relation was found between duration of venom immunotherapy and relapse risk. The relapse rate was higher among patients with high levels of specific IgE before and after immunotherapy. During therapy, the mean level of specific IgE decreased. This decline persisted in the 3 following years. No relapses of sting reactions were observed among patients without detectable specific IgE. Conclusion: Discontinuation of venom immunotherapy appears safe for patients with pretreatment IgE antibodies if these antibodies can no longer be detected during immunotherapy. For the remaining patients, a treatment period of 3 years may suffice. After discontinuation of immunotherapy, a clinical sting challenge can be considered to estimate the patient's current grade of hypersensitivity. (J Allergy Clin Immunol 1997;100:767-70.)     

Wasp venom immunotherapy induces a shift from IL-4-producing towards interferon-gamma-producing CD4+ and CD8+ T lymphocytes

BACKGROUND: Venom immunotherapy (VIT) has proven to be very effective in hymenoptera venom anaphylaxis. However, the underlying immunoregulatory mechanisms of venom immunotherapy remain poorly understood. Recent studies measured the total amount of cytokine in culture supernatans, suggesting a shift in cytokine production from Th2 to a Th1 cytokine profile during VIT. We wanted to examine the contribution of specific T lymphocyte subpopulations, which is impossible using an extracellular method to determine cytokines in supernatants. OBJECTIVE: The present study was designed to evaluate the effect of VIT on the percentages of type 1 (IL-2, interferon-gamma (IFN-gamma)) and type 2 (IL-4) CD4+ and CD8+ T lymphocytes of patients with wasp venom anaphylaxis during immunotherapy. METHODS: Peripheral blood mononuclear cells of 20 individuals with a history of wasp sting anaphylaxis and a positive serum wasp venom specific IgE were isolated and in vitro stimulated with phorbol-12-myristate-13-acetate and ionomycin before VIT, at the end of a 5-day semirush VIT and at 6 months during VIT. Three-colour flow cytometric analysis was used for intracellular cytokine (IL-2, IFN-gamma, IL-4) detection in CD4+ (CD3+CD8-) T lymphocytes and CD8+ (CD3+CD8+) T lymphocytes. RESULTS: At the end of a 5-day semirush VIT, there was a significant decrease in percentage of IL-4-producing CD4+ and CD8+ T cells, compared with cytokine-producing cells before VIT (P = 0.0002 and 0.004). After 6 months of VIT, patients showed an increased number of IL-2-producing stimulated CD4+ and CD8+ lymphocytes compared with values before VIT (P = 0.002 and P = 0.0003). A higher amount of IFN-gamma-producing stimulated CD4+ and CD8+ cells was found after 6 months of VIT (P = 0.001 and P = 0.0006). There was no correlation between cytokine-producing cells and specific IgE for wasp. CONCLUSION: Venom immunotherapy induced a shift from IL-4-producing towards IFN-gamma-producing CD4+ as well as CD8+ T lymphocytes.     

Prevention and treatment of hymenoptera venom allergy: guidelines for clinical practice

Based on the knowledge of the living conditions and habitat of social Aculeatae a series of recommendations have been formulated which can potentially greatly minimize the risk of field re-sting. After a systemic sting reaction, patients should be referred to an allergy specialist for evaluation of their allergy, and if necessary venom immunotherapy (VIT). An emergency medical kit should be supplied, its use clearly demonstrated and repeatedly practised until perfected. This should be done under the supervision of a doctor or a trained nurse. Epinephrine by intramuscular injection is regarded as the treatment of choice for acute anaphylaxis. H1-antihistamines alone or in combination with corticosteroids may be effective in mild to moderate reactions confined to the skin and may support the value of treatment with epinephrine in full-blown anaphylaxis. Up to 75% of the patients with a history of systemic anaphylactic sting reaction develop systemic symptoms once again when re-stung. Venom immunotherapy is a highly effective treatment for individuals with a history of systemic reaction and who have specific IgE to venom allergens. The efficacy of VIT in yellow jacket venom allergic patients has been demonstrated also by assessing health-related quality of life. If both skin tests and serum venom specific IgE turn negative, VIT may be stopped after 3 years. After VIT lasting 3-5 years, most patients with mild to moderate anaphylactic symptoms remain protected following discontinuation of VIT even with positive skin tests. Longer term or lifelong treatment should be considered in high-risk patients. Because of the small but relevant risk of re-sting reactions, in these patients, emergency kits, including epinephrine auto-injectors, should be discussed with every patient when stopping VIT.     

Use of beta-blockers during immunotherapy for Hymenoptera venom allergy

BACKGROUND: Beta-blockers may aggravate anaphylactic reactions and interfere with treatment. There is therefore concern about their use in patients who have a history of anaphylaxis or are on allergen immunotherapy. Immunotherapy is the best available treatment for prevention of life-threatening anaphylaxis to Hymenoptera stings, which is often observed in elderly patients who have cardiovascular disease and therefore are on beta-blocker treatment. OBJECTIVE: To analyze the risk of beta-blocker treatment during venom immunotherapy. METHODS: We screened all 1682 patients with Hymenoptera venom allergy seen during a period of 34 months for immunotherapy, cardiovascular disease, and treatment with beta-blockers. RESULTS: Of the 1389 patients in whom immunotherapy was recommended, 11.2% had cardiovascular disease, and 44 of these were on beta-blockers before immunotherapy. In 31 of those, the drug was replaced before starting treatment. In 3 with coronary heart disease and 1 with severe ventricular arrhythmia, the drug was continued throughout immunotherapy. In 9, it was reintroduced after reaching the maintenance dose. In an additional 12 patients, beta-blockers were newly started during immunotherapy. Of 25 patients on beta-blockers during immunotherapy, 3 (12%) developed allergic side effects, compared with 23 (16.7%) of 117 with cardiovascular disease but without beta-blockers. Systemic allergic symptoms after re-exposure by sting challenge or field sting were observed in 1 of 7 (14.3%) with and 4 of 29 (13.8%) without beta-blockade. No severe reactions to treatment or sting reexposure were observed in patients with beta-blockade. CONCLUSION: Combination of beta-blockers with venom immunotherapy may be indicated in heavily exposed patients with severe cardiovascular disease.     

Salt-Sensitive Hypertension Resulting From Nitric Oxide Synthase Inhibition is Associated with Loss of Regulation of Angiotensin II in the Rat

In the Dahl salt-sensitive hypertensive rat, a diet containing L-arginine, the natural substrate for nitric oxide synthase, abrogates the hypertension. We postulated that nitric oxide synthase inhibition might induce a salt-sensitive form of hypertension and that this salt sensitivity might be linked to a loss of the regulatory effect of sodium ingestion on angiotensin II (Ang II) and angiotensinogen. Male Wistar-Kyoto rats were randomised to a diet containing 0.008 %, 2.2 % or 4.4 % sodium chloride and to treatment with the NO synthase inhibitor L-NAME (10 mg kg(-1) day(-1)) in the drinking water, or drinking water alone (Controls) for 4 weeks. Blood pressure was measured by tail cuff plethysmography twice weekly. After 4 weeks, the rats were anaesthetised and truncal blood collected for determination of angiotensinogen, renin, angiotensin I (Ang I), Ang II and aldosterone concentrations as well as angiotensin-converting enzyme (ACE) activity. Systolic blood pressure increased with increasing dietary sodium intake in the L-NAME-treated rats (P < 0.05). Plasma renin and aldosterone concentrations decreased with increasing dietary sodium intake in both Control and L-NAME-treated rats. Ang I and ACE activity were unchanged by increasing dietary sodium intake. In contrast, the plasma concentration of Ang II and angiotensinogen increased with increasing dietary sodium (P < 0.05 and P < 0.005, respectively). Treatment with the Ang II receptor blocker, losartan, reversed the blood pressure increase. We conclude that treatment with L-NAME induces an increase in blood pressure that is at least in part salt sensitive. Further, the salt-sensitive component appears to be Ang II-dependent, as it was associated with increasing plasma Ang II levels and could be reversed by treatment with an Ang II receptor antagonist.     

Effect of rush immunotherapy (RIT) on Hymenoptera allergy]

In our country approximately forty people die every year from anaphylaxis caused by hymenoptera stings. Between 1988 and 1996, 48 patients, who had experienced a systemic reaction to hymenoptera sting and were proved to have specific IgE antibodies to wasp, yellow or both (RAST score > or = 2), received rush immunotherapy (RIT) using venom extracts in our hospital. Fifteen patients had re-sting after RIT. Fourteen out of the 15 patients showed only local reaction to the hymenoptera re-sting and one patient had mild generalized symptoms. Although one patient showed mild generalized uriticaria during RIT, no adverse reaction occurred during and after RIT in the other subjects. Follow-up studies on the titers of serum total IgE antibodies and hymenoptera specific IgE and IgG4 antibodies revealed that total and specific IgE antibodies transiently increased one month after RIT and returned to their baseline values by 6 months after RIT, while specific IgG4 antibodies continued to gradually increase up to al least 3 years after RIT. These results demonstrates that RIT is effective in prevention of a systemic reaction to hymenoptera re-sting and an increase in the titer of hymenoptera specific IgG4 antibodies may at least partly explain the efficacy of RIT.     

Influence of total IgE levels on the severity of sting reactions in Hymenoptera venom allergy

BACKGROUND: Detection of specific IgE for Hymenoptera venoms and skin tests are well established diagnostic tools for the diagnosis of insect venom hypersensitivity. The aim of our study was to analyze the effect of total IgE levels on the outcome of generalized anaphylactic reactions after a Hymenoptera sting. METHODS: Two hundred and twenty patients allergic to bee, wasp, or European hornet venom were included in the study. Their specific and total IgE levels, serum tryptase levels, skin tests, and sting history were analyzed. RESULTS: In patients with mild reactions (grade I, generalized skin symptoms) we observed higher total IgE levels (248.0 kU/l) compared to patients with moderate reactions (grade II, moderate pulmonary, cardiovascular, or gastrointestinal symptoms; 75.2 kU/l) and severe reactions (grade III, bronchoconstriction, emesis, anaphylactic shock, or loss of consciousness; 56.5 kU/l; P < 0.001). Accordingly, 25% of the patients with low levels of total IgE (<50 kU/l), but no individual with total IgE levels >250 kU/l, developed loss of consciousness (P = 0.001). Additionally, specific IgE levels were related to total IgE levels: Specific IgE levels increased from 1.6 to 7.1 kU/l in patients with low (<50 kU/l) and high (>250 kU/l) total IgE levels, respectively (P < 0.001). Specific IgE levels correlated inversely to the clinical reaction grades, however, this trend was not statistically significant (P = 0.083). CONCLUSION: Patients with Hymenoptera venom allergy and high levels (>250 kU/l) of total IgE, predominantly develop grade I and grade II reactions and appear to be protected from grade III reactions. However, this hypothesis should be confirmed by extended studies with sting challenges.     

Bee venom allergy in beekeepers and their family members

PURPOSE OF REVIEW: To analyze prevalence of allergic sting reactions, including the clinical and diagnostic features as well as management options in a population heavily exposed to honeybee stings such as beekeepers and their family members. RECENT FINDINGS: The higher sting frequency is associated with an increased prevalence of allergic sting reactions. Major risk factors for allergic sting reactions in beekeepers are: fewer than 10 annual stings, an atopic constitution and symptoms of upper respiratory allergy during work in the beehive. Bee venom allergic beekeepers have higher levels of bee venom-specific IgG but lower skin sensitivity and bee venom-specific IgE than normally exposed bee venom allergic patients. Safety of bee venom immunotherapy is higher in beekeepers than in allergic controls, while efficacy of this treatment is similar in both groups. SUMMARY: Beekeepers and their family members are at an increased risk of severe sting anaphylaxis and therefore need especially careful instruction with regard to avoidance of re-exposure, emergency treatment and specific immunotherapy with bee venom.     

Clinical reactivity to insect stings

PURPOSE OF REVIEW: Allergy to insect stings remains a hazard worldwide and is the object of updated guidelines on management. This paper reviews the various clinical responses that may occur following an insect sting. RECENT FINDINGS: Although the general population is at slight risk, certain groups are more susceptible, including occasionally stung adult male agricultural workers, hobby honey beekeepers and family members of beekeepers. Individuals with systemic mastocytosis are especially reactive to stings. The body of evidence attesting to the marked beneficial effect that 3-5 years of venom immunotherapy has on the natural history of hymenoptera hypersensitivity is especially evident in children. Case reports indicate other consequences of hymenoptera sting, and these are discussed. SUMMARY: Hypersensitivity to insect stings is common and may be life threatening. Although most occur away from medical facilities, their diagnosis and management are important to a wide spectrum of health care professionals. Most reactions to stings are nonallergic manifestations of the venom's toxic effects, and present as erythema, pain and swelling about the sting site. Fire ants bite with their mandibles and pivot their head, inflicting multiple stings that usually result in a sterile pseudopustule at the site. Hypersensitivity responses to venom range from large local reactions (a late-phase response) to life-threatening anaphylaxis. Venom-specific immunotherapy is highly effective in the modification of subsequent reactions to hymenoptera stings, as is whole body extract for fire ant stings.     

High sensitivity of basophils predicts side-effects in venom immunotherapy

BACKGROUND: Systemic side-effects of venom immunotherapy (VIT) represent a considerable problem in the treatment of patients allergic to Hymenoptera venom. We examined the hypothesis whether basophil responsiveness might be connected with the adverse reactions to VIT. METHODS: Basophil surface expression of activation marker CD63 induced by different concentrations of honeybee and wasp venom (0.1 and 1 mug/ml) was measured by flow cytometry in 34 patients with history of systemic anaphylactic reactions to Hymenoptera sting just before rush honeybee or wasp VIT. RESULTS: Eleven of 34 patients had systemic anaphylactic reaction (Mueller grades I-III) and one patient a large local reaction to VIT. In those 12 patients, median percentage of activated basophils after stimulation with VIT-specific venom in concentration of 0.1 microg/ml was 99% (range: 17-195) of value reached with stimulation with 1 microg/ml. Side-effects occurred in all patients with 0.1/1 ratios over 92% (eight of 12). In contrast, in 22 patients with no side-effects, the median 0.1/1 ratio was 25% (range: 2-92). These concentration-dependent activation ratios were significantly different between the groups with and without side reactions (P < 0.0001). We also show significant positive correlation of the occurrence/clinical grade of the side-effects with individual ratios of CD63 basophil response (r = 0.73, P < 0.0001). CONCLUSION: The results suggest that increased basophil sensitivity to allergen-specific in vitro stimulation is significantly associated with major side-effects of VIT.     

Late-onset allergic reactions, including serum sickness, after insect stings

Allergic reactions after insect stings may have a delayed onset, differing from the usual immediate anaphylactic pattern. Ten patients, aged 6 to 78 years, had allergic reactions 1 to 2 weeks after an insect sting. Six patients had had multiple stings preceding the reaction. In two instances, immediate anaphylaxis also occurred. Four of the 10 patients had serum sickness-type reactions; two other patients had more severe anaphylactic symptoms, including throat edema. All patients in this group had venom-specific IgE; four of the 10 patients had serum venom-specific IgG. Eight patients subsequently received venom immunotherapy (VIT). There have been no reactions from seven re-stings. Five patients had generalized hives starting 6 to 24 hours after an insect sting. All patients in this group had venom-specific IgE; three patients have received VIT. Two other patients developed hives, one with throat edema 3 days after an insect sting. Both patients had high titers of serum venom-specific IgE; neither patient has received VIT, one patient because of extreme sensitivity. These observations suggest that after an insect sting, patients may develop delayed-onset allergic symptoms that range from typical anaphylaxis to serum sickness and are mediated by venom-specific IgE. VIT is recommended for patients with these reactions.     

Dysregulation of angiotensin II synthesis is associated with salt sensitivity in the spontaneous hypertensive rat

(1) Salt sensitive hypertension, which occurs as a result of treatment with nitric oxide synthase inhibitors, is associated with a loss of the usual down-regulatory effect of dietary sodium on angiotensin II (Ang II) synthesis. In the spontaneous hypertensive rat (SHR), which suffers a relative NO deficiency, the hypertension is in part salt sensitive. We sought to determine therefore whether the salt sensitive component to the hypertension was associated with a loss of the regulatory effect of dietary sodium on Ang II synthesis. (2) Male SHR were placed on low, intermediate or high salt diets for 4 weeks and their blood pressure recorded. After 4 weeks, blood was collected for determination of renin, angiotensinogen, Ang I, Ang II and aldosterone concentrations, as well as ACE activity. (3) The increase in systolic blood pressure in rats on the high salt diet was significantly greater than in those on the low (P < 0.005) and intermediate salt diets (P < 0.0005). Plasma renin and aldosterone concentrations and ACE activity decreased with increasing dietary sodium. However, the concentrations of Ang II and angiotensinogen both increased in the rats on the high salt diet (Ang II: P < 0.05; angiotensinogen: P < 0.05). (4) We conclude that the hypertension in the SHR is in part salt sensitive and that this salt sensitive component is associated with a loss of the normal down-regulatory effect of dietary sodium on Ang II and angiotensinogen synthesis.     

Possible circadian variation of serum mast cell tryptase concentration

BACKGROUND: A temporarily elevated level of serum mast cell tryptase (ST) indicates mast cell activation and occurs in systemic anaphylactic reactions (SAR). We measured ST following a sting challenge in vespid venom-allergic patients treated with venom immunotherapy (VIT) and in healthy controls, respectively. AIM OF THE STUDY: To assess changes of ST over time in vespid venom-allergic patients at the occasion of a re-sting and in healthy controls. METHODS: A sting challenge was performed in 20 patients on vespid VIT to monitor efficacy of VIT. ST was measured between 9.00 and 10.00 a.m. (baseline). Sting challenge was performed at 2.00 p.m., and ST was determined again 20 min, 90 min and 18 h later. Measurements at corresponding times of the day were done in nine healthy controls. RESULTS: One patient developed a mild SAR to the sting challenge which was associated with a temporary increase of ST. In the other 19 patients who tolerated the sting challenge without SAR ST decreased significantly by 18.0% (median, range 8.3-36.7%). Twenty minutes after the sting when compared with baseline levels (P < 0.001), a significant decrease of ST was still present after 90 min (median 13.7%) (P < 0.001), but not after 18 h (P = 0.57). A comparably significant temporary decline was found in controls. CONCLUSIONS: The temporary decline of ST in patients and in controls suggests a circadian variation of ST concentration. A normal diurnal pattern of ST concentration after sting challenge is associated with successful treatment.     

Studies on the activity of the renin-angiotensin-aldosterone system (RAAS) in patients with cirrhosis of the liver

Summary Plasma renin activity (PRA), plasma renin concentration (PRC), angiotensinogen, angiotensin II (AT II) and plasma aldosterone were determined by radioimmunoassay in 77 patients with cirrhosis of the liver [group I: with ascites, untreated (n=23); group II: patients with ascites during treatment (n=32); group III: after removal of fluids, but under further spironolactone therapy (n=10); group IV: untreated subjects without ascites (n=12)]. With the exception of decreased angiotensinogen values in all groups ranging between 39% (group IV) and 73% (group III) no significant changes of the other parameters of the RAAS were found in untreated patients. A highly significant increase of PRA, PRC, AT II and plasma aldosterone was observed in treated cirrhotics with (group II) or without (group III) ascites. In the total series of patients AT II was closely related to PRA, PRC and aldosterone emphasizing again the predominant role of AT II to stimulate aldosterone secretion. Plasma sodium was inversely correlated to PRA, PRC, AT II and aldosterone, but no relationship was detected between these parameters of the RAAS and plasma potassium.Our results indicate that hyperaldosteronism in cirrhosis appears unlikely to be the major determinant of avid renal sodium retention and ascites formation. An increased activity of the RAAS is most often initiated by therapeutic factors and/or markedly altered electrolyte metabolism. Therefore, basal conditions of the patients to be studied must be well defined to exclude any artificially induced stimulation of the RAAS.     

Evaluation of bee sting allergy by skin tests and serum antibody assays.

We studied 55 subjects who had had anaphylactic reactions to bee stings within the previous 3 years. 38 out of 54 tested had IgE antibody to honey bee venom (HBV) as measured by radioallergosorbent test (RAST). On skin testing, 30 out of 34 had a positive test to HBV. Of these, 26 had a positive RAST. A positive skin test to HBV at high dilution or else a high anti-HBV RAST score appeared to identify those who, in a 6-month follow-up period, were at risk of developing further anaphylaxis following bee stings or immunotherapy. Of the two tests, RAST appeared to be the less sensitive. Measurements of IgG antibody to phospholipase A were seldom available for the period immediately preceding an anaphylactic episode and proved to be a poor means of predicting the liability to bee sting anaphylaxis in subsequent months.     

Augmented intrarenal and urinary angiotensinogen in hypertension and chronic kidney disease

Activated intrarenal renin–angiotensin system plays a cardinal role in the pathogenesis of hypertension and chronic kidney disease. Angiotensinogen is the only known substrate for renin, which is the rate-limiting enzyme of the renin–angiotensin system. Because the levels of angiotensinogen are close to the Michaelis–Menten constant values for renin, angiotensinogen levels as well as renin levels can control the renin–angiotensin system activity, and thus, upregulation of angiotensinogen leads to an increase in the angiotensin II levels and ultimately increases blood pressure. Recent studies using experimental animal models have documented the involvement of angiotensinogen in the intrarenal renin–angiotensin system activation and development of hypertension. Enhanced intrarenal angiotensinogen mRNA and/or protein levels were observed in experimental models of hypertension and chronic kidney disease, supporting the important roles of angiotensinogen in the development and the progression of hypertension and chronic kidney disease. Urinary excretion rates of angiotensinogen provide a specific index of the intrarenal renin–angiotensin system status in angiotensin II-infused rats. Also, a direct quantitative method has been developed recently to measure urinary angiotensinogen using human angiotensinogen enzyme-linked immunosorbent assay. These data prompted us to measure urinary angiotensinogen in patients with hypertension and chronic kidney disease, and investigate correlations with clinical parameters. This short article will focus on the role of the augmented intrarenal angiotensinogen in the pathophysiology of hypertension and chronic kidney disease. In addition, the potential of urinary angiotensinogen as a novel biomarker of the intrarenal renin–angiotensin system status in hypertension and chronic kidney disease will be also discussed.     

Clinical features of acute anaphylaxis in patients admitted to a university hospital: an 11-year retrospective review (1985-1996).

BACKGROUND: Although anaphylaxis is considered a life-threatening event, there is a lack of information on the clinical characteristics at presentation, both in adults and in children. OBJECTIVE: To describe in a nonselected population the clinical characteristics and the treatments of acute anaphylaxis triggered by different agents. METHODS: This is a retrospective review of the clinical features of 113 episodes of acute anaphylaxis resulting in admission to a university hospital. Initially, the 107 patients visited the emergency room and were then admitted to the hospital. RESULTS: Most anaphylactic events (63%) occurred at home. The most frequent symptoms involved the respiratory system (78%) and the skin (90%). Drugs, especially nonsteroidal anti-inflammatory drugs and antibiotics, were the most frequent cause of anaphylaxis in adults (49%). Patients with drug-induced anaphylaxis were older and more often had cardiovascular symptoms (hypotension and tachycardia) (P = 0.0064). Hymenoptera venom was the second most frequent cause of anaphylaxis (29%). Most of the patients with hymenoptera venom anaphylaxis were male (80%) and more frequently they had no history of atopy (P = 0.012). In food-induced anaphylaxis, the cardiovascular system was less likely to be involved (P < 0.05) (39%). Seafood seems to be frequently involved in food-induced anaphylaxis in our area. Specific immunotherapy-induced anaphylaxis occurred more often in younger patients (P = 0.032). Epinephrine seems to be underused in Italy (only 15% of patients received it), especially for respiratory symptoms. CONCLUSIONS: Anaphylaxis triggered by different agents may have different clinical presentations and may occur in different types of patients. In Italy, the inadequate use of epinephrine for anaphylaxis treatment needs to be publicized to both physicians and the general population.