Site of entry of kininase II into renal tubular fluid.

The stop-flow technique was used to determine the site of entry of kininase II into tubular fluid in dogs. Stop-flow patterns were constructed for kininase II, p-aminohippurate, sodium, and potassium. The proximal tubule was localized by the peak of p-aminohippurate concentration and the distal tubule by the minimum sodium concentration. In the stop-flow pattern for kininase II, three peaks (a, b, and c) were observed. A main peak (a), located 2.25 +/- 0.45 ml distal to the p-aminohippurate peak (p less than 0.01) and 3.75 +/- 0.31 ml proximal to the minimum sodium concentration (p less than 0.001), was observed in all experiments. Peak c, located 2.6 +/- 0.4 ml (p less than 0.01) proximal to the p-aminohippurate peak, was observed in five dogs. Peak b appeared in five dogs and was always located 2.0 ml distal to the minimum sodium concentration. This peak was coincident with the potassium peak. Only two of eight experiments showed all three peaks. These results showed that the major kininase II entry into the tubular fluid is near the p-aminohippurate peak and that distal entry occurred in 63% of the dogs.

Kinin receptors mediating the effect of bradykinin on gastric acid secretion.

Kinins, and bradykinin in particular, can affect electrolyte transport in different segments of the intestine, thus being able to stimulate chloride secretion. Since the stomach is the main chloride secretory unit in the gastrointestinal tract, we have investigated the effect of bradykinin on acid secretion in the isolated frog (Rana catesbeiana) gastric mucosa. Bradykinin [2 x 10(-8) to 2 x 10(-6) M] and des-Arg9-bradykinin [2 x 10(-9) to 2 x 10(-7) M] were able to stimulate acid secretion in a dose-dependent manner. The bradykinin [2 x 10(-7) M] and des-Arg9-bradykinin (2 x 10(-8) M]-induced acid secretion was unaffected by Thi5,8,D-Phe7-bradykinin [2 x 10(-7) to 2 x 10(-5) M], a B2-kinin receptor antagonist. Interestingly, the B1-kinin receptor antagonist, des-Arg9-(Leu8)-bradykinin [2 x 10(-7) to 2 x 10(-5) M] blocked both bradykinin- and des-Arg9-bradykinin-stimulated acid secretion. Although the kininase I inhibitor, D-L-mercapto-methyl-3-guanidino-ethyl-propanoic acid [2 x 10(-6) and 2 x 10(-5) M] had no effect on des-Arg9-bradykinin-induced acid secretion, it inhibited the response to bradykinin. We conclude that bradykinin requires, at least in part, hydrolysis to des-Arg9-bradykinin to increase gastric acid secretion and that its effect is mediated by B1-kinin receptors.

Effects of purified scorpion toxin (tityustoxin) on gastric secretion in the rat.

An i.v. bolus injection of a purified scorpion toxin (tityustoxin, TsTX) in urethane anesthetized rats induced a dramatic increase in volume, acid and pepsin output of gastric juice and a significant decrease in its pH. The maximal stimulatory effects of TsTX on gastric secretion were obtained with a dose of 0.25 mg/kg acting for 60 min. Hexamethonium did not prevent the gastric secretion evoked by TsTX, whereas atropine or cimetidine abolished partially or totally the toxin effects. Acute bilateral cervical or abdominal vagotomy did not prevent the effects of TsTX on gastric secretion, but chronic abdominal vagotomy abolished the toxin effects. Chronic antrectomy diminished the effect of TsTX on gastric secretion. In the pylorus-ligated group of rats, the gastric secretion evoked by TsTX was not different from that observed in the pylorus-intact group. It is concluded that the changes in gastric volume, acid output, pH and pepsin output induced by TsTX in the rat are due to the release of chemical mediators from postganglionic autonomic nerve fibers which would act through muscarinic and H2-receptors stimulation.

A comparison of new nonsedating and classical antihistamines in the treatment of primary acquired cold urticaria (ACU).

The efficacy of the new nonsedating antihistamines loratadine and cetirizine was compared in a randomized, single-blind, crossover, controlled study with that of the classical antihistamines cyproheptadine and ketotifen in seven patients with primary acquired cold urticaria (ACU). The patients received each of the four drugs for 14 consecutive days with a 7-day interval between drugs. We evaluated clinical symptomatology, adverse effects, minimum time of cold contact stimulation required to induce an immediate coalescent wheal (CSTT), and inhibition of histamine-induced wheal response. Both loratadine and cetirizine showed suppression of symptoms with infrequent adverse effects. Important side-effects were observed in patients receiving cyproheptadine. Improvement in CSTT was statistically significant for all drugs compared with baseline values, without differences among them. The histamine-induced skin test was significantly inhibited by all antihistamines. Wheal reductions were 34.6% for loratadine and 50.9% for cetirizine. This study suggests that both loratadine and cetirizine may be effective in the treatment of primary ACU.

Short-term treatment of asthma with budesonide versus placebo.

The effects of the topical steroid budesonide on bronchial hyperreactivity were evaluated in a patient group (A, n = 17) and a placebo-controlled patient group (B, n = 11). Group A was given budesonide 400 micrograms/12 h for 4 weeks and 200 micrograms/12 h for four more weeks. The drug proved efficient in controlling asthma clinically and improving the spirometric parameters: FVC (p < 0.05), FEF50 (p < 0.05) and FEV1 (p < 0.01). Bronchial hyperreactivity (PD20) decreased moderately in the treatment group (p < 0.1). On the contrary, basal spirometry and PD20 worsened in the control group. Some patients in group A showed peripheric eosinophilia (2/15) or in secretions (9/15), which persisted in one patient at end of treatment. Budesonide was effective in the clinical and spirometric control of asthma. We conclude that for a better assessment of the treatment of bronchial hyperreactivity with budesonide, the drug must be administered for a longer period of time. The differences between this study and previous ones is that the improvement in PD20 can be explained by the different characteristics of the patients selected for this study.

Booster responses in the study of allergic reactions to beta-lactam antibiotics.

The observation of negative skin and challenge tests to beta-lactams in some patients with prior histories of reactions to these antibiotics led us to develop a protocol ("booster study") which systematically included the performance of skin and challenge tests to beta-lactams ten to thirty days after the study to confirm the negative results. From a total of 430 patients who came to our outpatient clinic because of a reaction to a beta-lactam or unknown antibiotic, 249 completed the study. Out of the patients who completed the second phase, or "booster study," the results were positive in the first phase, or conventional study in 42 patients, and negative in 207. The booster study was negative in 197 patients (95 percent) and positive in ten patients (5 percent). Skin tests were positive in 5 of them (penicilloyl-polylysine: 5; benzylpenicillin: 3; amoxicillin: 2; minor determinant mixture: 1), and 5 patients developed an allergic reaction after rechallenge (benzylpenicillin: 4; amoxicillin: 1). One patient with both negative skin tests and amoxicillin oral challenge in the booster study developed an immediate generalized urticaria with the oral intake of amoxicillin one month later at home; skin tests became positive at that moment. The negative results in the first phase of the study and the development of positive results in the second phase could be due to the existence of an immunological amnestic reaction or to sensitization after reexposure to beta-lactams in the diagnostic procedures.

[Eosinophilic gastritis: its spontaneous resolution]. / Gastritis eosinofílica: resolución espontánea.

A 34-year-old man presented with acute epigastric pain. Laboratory studies disclosed a total eosinophil count 7.7 x 10(9)/l. The pathological diagnosis was eosinophilic gastritis. There was a spontaneous resolution, and no treatment was required. Investigations for allergic disorders gave negative results.

A stop flow analysis of the effects of intrarenal infusion of bradykinin.

The effects of bradykinin (Bk) on renal function were investigated in the in situ dog kidney by means of the stop-flow method. Bradykinin, when injected into the renal artery of the dog, reduced the proximal reabsorption of sodium and water and decreased the secretion of p-aminohippuric acid (PAH). Because filtration was stopped during the experiments, there was no alteration of the peritubular colloid osmotic pressure, and geometric changes of the tubules were minimized. This enabled us to conclude that Bk decreased the transport efficiency of sodium and PAH. The demonstration of the inhibitory effects of Bk on PAH secretion suggests that the inhibition of acid secretion is dependent not only upon the increase in medullary blood flow, but also upon a reduction of the cortical clearance of PAH.

Urticaria from erythromycin.

We report an adverse cutaneous reaction (urticaria) due to erythromycin. A positive skin prick and leukocyte histamine release tests, as well as a positive single-blind, placebo controlled oral challenge to erythromycin, strongly suggest an IgE mediated hypersensitivity mechanism.

Egg protein sensitization in patients with bird feather allergy.

We have studied the hypersensitivity to hen's egg protein and chicken meat in 25 adults with a previous diagnosis of bronchial asthma and rhinoconjunctivitis due to bird feather sensitization. Seventeen of the 25 reported good tolerance to the ingestion of egg and chicken meat. The skin tests were negative to both antigens in 15 of them, and positive for egg in two. All 17 patients had negative RAST to chicken meat and egg protein. The remaining eight patients had intolerance to egg, and three of them also to chicken meat ingestion; in seven of the eight cases allergic to egg, the alimentary intolerance began after the clinical symptoms of bird feather sensitization. In all eight cases the skin tests were positive to egg yolk, and in five of them also to egg white and chicken meat. These patients evidenced specific serum IgE antibodies to egg yolk, four of them to egg white, and seven to chicken meat. These results demonstrate the high frequency (32%) of the association of sensitization to egg proteins, particularly egg yolk, in a selected population of patients with known allergy to bird feathers, thus suggesting that in some patients feather sensitization could trigger or somehow facilitate the later sensitization to egg yolk proteins.

Acute volaemic changes modify the gastroduodenal resistance to the flow of saline in anaesthetized dogs.

The effect of acute and sequential volaemic changes on the gastroduodenal flow of saline was assessed in 23 anaesthetized dogs following two different experimental protocols. Hypervolaemia, by i.v. infusion of saline, induced a gradual decrease on gastroduodenal flow which amounted to 76% below control values (P less than 0.001) when volaemic expansion attained 5% of body weight. This effect was volume dependent (17% increase on gastroduodenal flow per volume of infused saline equivalent to 0.5% of body weight, P less than 0.001), lasted for at least 90 minutes after infusion was completed and was also obtained by expanding previously bled animals. Hypovolaemia due to bleeding was followed by an increase on gastroduodenal flow of about 88% above control values (P less than 0.05) when haemorrhage was equal to 3% of body weight. This effect was also volume dependent (23% increase on gastroduodenal flow per volume of blood shed equivalent to a 0.5% of body weight, P less than 0.01) and was reversed after blood volume was restored. These modifications in the resistance of the gastroduodenal segment to the flow of liquid due to acute volaemic changes suggest that the extracellular fluid volume modulates the contractile activity of the gastroduodenal portion of the gut possibly to set a gastroduodenal handling of liquid adequate to cope with volaemic imbalances.

Analysis of cross-reactivity between sunflower pollen and other pollens of the Compositae family.

The sera of 20 patients with Compositae pollen allergy were investigated for the presence of IgE antibodies reacting against sunflower pollen by means of RAST and immunoblotting studies. Thirteen IgE-binding bands were detected with molecular weights ranging from 14.4 to 94 kd. Two of these bands, with molecular weights of 24 and 25 kd, contained major allergens that reacted strongly with 100% (24 kd) and 95% (25 kd) of the sera, respectively. Cross-reactivity between sunflower and other Compositae pollens (mugwort, marguerite, dandelion, golden rod, and short ragweed) was revealed by RAST and immunoblotting inhibition experiments. Mugwort pollen exhibited the greatest degree of allergenic homology (cross-reactivity) with sunflower pollen, whereas at the other end of the spectrum, short ragweed showed less cross-reactive epitopes.

[Latex sensitization in 28 patients]. / Sensibilización a látex en 28 pacientes.

We present a review of 28 cases of sensitization to latex. Skin prick test for latex was performed in subjects suspected of having allergy to latex and many fruits. Recently, many publications have evidenced the importance of sensitization to latex. There are well documented cases of intraoperatory anaphylaxis. Frequently, this happens to children with congenital urologic malformations, spina bifida or myelomeningocele, who undergo numerous surgical operations and vesical catheterizations. Latex-induced allergy also affects health professionals, since they are continuously in contact with latex-derived materials. There are other studies that relate latex-induced allergy to several fruit allergies (mainly chestnuts, bananas and avocados). In recent literature some discrepancy exists about the reliability of the prick test and the sensibility of in vitro diagnostic methods. We analyze 28 cases of latex sensitization from our clinic, comparing the most severe cases with the remaining subjects. Atopia antecedents were present in 82%, sub-clinical sensitization in 10 cases, urticaria/angioderma in 5, anaphylaxis in 9, and contact dermatitis in 4. Women were majority, with 22 cases versus 6 males. In patients with latex-induced anaphylaxis, the significantly most frequent feature was previous professional exposure to latex (p = 0.004). Specific IgE was measured by radioallergosorbent test (RAST), finding the highest values in the most severe clinical cases (p=0.0016), comparable to the results of the prick test, which still is the best diagnostic method. In our experience, banana and chestnut-induced allergies were the allergies most frequently associated to latex-induced allergy. There were no adverse reactions in any patient after the prick test.

Sulfite-induced urticaria.

Metabisulfite sensitivity is being described with growing frequency. Sulfites are used in food, drinks, and drugs. Adverse reactions to apparently nontoxic doses have been described. Exposure of sensitive persons to sulfites has produced asthma, and occasionally other adverse reactions in nonasthmatic patients. We present a case of urticaria induced by metabisulfites. During the previous 2 years the patient had suffered episodes of urticaria and angioedema limited to the face, neck, upper thorax, and dysphonia without asthma after the ingestion of food and drinks containing sulfites. Oral challenge with 25 mg of potassium metabisulfite elicited urticaria on the face and neck, nasal itching, rhinorrhea, and dysphonia. Prick and intradermal tests were negative. Two further challenges with the same doses were also positive. One of these was controlled with placebo, 30 minutes after oral administration of 400 mg sodium cromolyn; the second was carried out 90 minutes after oral administration of 5000 micrograms cyanocobalamin. We have been unable to identify a pathogenic mechanism.

Sensitization to Olea europaea: geographical differences and discrepancies.

Thirty eight patients from two geographical areas of Spain, with great differences in Olea europaea pollen counts were studied to investigate their in vivo and in vitro immune response to this pollen as a consequence of their different environmental allergen exposure. They were distributed in two groups (13 from Madrid, and 25 from Jaén). Skin sensitivity was assessed by a prick-test dose-response bioassay using serial dilutions of a biologically standardized allergen extract of O. europaea. Serological immune response was evaluated measuring specific antibody levels (IgE, IgG, IgG1 and IgG4). The patients from Jaén, who have a higher exposure to olive pollen, had higher levels of specific antibodies but significantly smaller wheal sizes than a similar patient population form the Madrid area, where olive pollen is not so copious. There is a great discrepancy between the results of skin prick tests (low cutaneous reactivity associated with high allergenic environmental load) and the levels of specific IgE to the olive pollen. While the level of specific antibodies increases with the allergenic load, the capacity to release mediators seems to be decreased, at least in the skin. Further studies are needed to evaluate if these findings also occur in other target organs with appropriate challenge tests (conjunctival, nasal and bronchial). This pattern should be studied with other allergens in large patient populations.