[Skin reactivity in the histamine-equivalent skin test in hypersensitivity to grass pollen]. / Reaktivnost koze i sistem "prik-test jednak histaminskom" kod preosetljivih na polene trava.

INTRODUCTION: Skin prick-test has been accepted as one of diagnostic criteria for atopic diseases. In accordance with the recommendations of the EAACI (European Academy of Allergy and Clinical Immunology), the Subcommittee for skin testing, allergen specific skin prick-test should be estimated in relation to positive control (histamine hydrochloride in the HEP system/histamine equivalent prick/) [1-4]. The purpose of this study was to establish a recording system of skin sensitivity to allergen by using HEP method in our patients. MATERIAL AND METHODS: The study was performed in 75 persons (49 females, 26 males, mean age 34.6 years) suffering from atopic diseases (hay fever, allergic asthma or rhinoconjunctivitis) and susceptible to one of pollen allergens. Skin prick tests were performed and recorded as said before [2-6]. We used a house standardized (Torlak Institute) allergen solution of 5000 AU/mL (pollen of Dactylis glomerata, Lolium perennae, Phleum pratense), 7500 AU/mL (Phleum pratense) and 10,000 AU/mL (Phleum pratense) and histamine-hydrochloride solution (1 mg/mL and 10 mg/mL). Total and allergen specific serum IgE was made before the study by ELISA immunoassay (Pharmacia, Uppsala, EIA RAST Phadesim) in all selected persons and results were recorded in Phadebas RAST unit given by the manufacturer. According to the serum concentration of specific IgE, patients were classified into groups (low susceptibility, intermediate sensitivity and highly susceptible persons). Skin reactions were recorded according to histamine skin sensitivity (as reaction equal or larger in diameter than histamine papule). Additionally, measured allergenic and histamine wheal were sorted and frequency of positive tests was calculated. Skin testing was performed with the approval of the Ethic Committee of our Centre and with the written patients' consent. For statistical analysis we used chi 2 test, regression analysis and Kolmogar-Smirnov nonparametric test. Results for the confidence of 95% (p < 0.05), were considered significant. RESULTS: In a group of 30 persons, susceptible to Phleum pratense pollen (Table 1, Graph 1 and 2), it was found that the number of positive tests was equally distributed among groups; it was dependent on the allergen concentrations, and was higher when using H1 (p < 0.01). When H10 was used as reference solution, only allergens of the highest concentration provided a significant number of positive tests (p < 0.01). There was no difference among groups of patients depending on the concentration of used histamine solution. In all 75 persons, we estimated skin-prick test performed by allergen solution of 5000 AU/mL and compared it with HI reaction. It was calculated that the most frequent histamine papule diameter was 3 mm and this value was farther used as the end-diameter in HEP system. Patients were classified in groups on the basis of serum IgE concentrations (RAST). The estimation of criterion positivity revealed the highest significance by using criterion Ap > Hp (p < 0.001). At the same time, if the criterion Ap > 2Hp was used we were sure that 99% of our patients were highly sensitive to allergen we tested. DISCUSSION: In the study it was established that allergen concentration of 5000 AU/mL and histamine solution of 1 mg/mL are sufficient to estimate skin-prick test in the HEP system. We found that the end diameter of histamine-papula was 3 mm. This finding suggests the good utility of HEP system. In addition, it has been proven that absolute value of papula diameter is not a critical parameter for the estimation of positivity or discrimation among patients regarding their susceptibility to allergen. By this system we found that criterion Ap > Hp, provides a significantly higher number of positive tests (p < 0.001). The recommended criterion Ap > Hp gives no discrimination among tested groups of patients, while using the criterion Ap > 2Hp we diagnosed highly susceptible persons (p < 0.01). (ABSTRACT TRUNCATED

[Total allergen-specific IgE antibodies in the serum and skin reactivity induced by a mixture of pollens in allergic individuals]. / Ukupna alergen-specificna IgE antitela u serumu i reakcija koze izazvana mesavinama polena kod preosetljivih osoba.

Skin puncture test is fast and precise method for revealing IgE-mediated allergen hypersensitivity. In the diagnosis of pollinosis and other atrophic diseases, expensive tests for revealing the allergen-specific IgE antibodies in the serum are frequently inaccessible. The subject of our investigation was how and if the skin test with mixture of pollen could replace the expensive in-vitro method in diagnostic procedure. In 41 patients with pollinosis were performed skin tests by the mixture of pollen of grass, weeds and trees (produced by Torlak Institute, Belgrade) and determined the concentration of overall and allergen-specific IgE serum (EIA, enzyme immuno-assay, Pharmacia Uppsala; RAST Phadesim, multidisk, Pharmacia). Obtained results pointed out that the sex of investigated subjects did not influence the size of skin reaction in case when the pollen mixture (grass, weed or trees) was used. With high significance rate was established that in skin puncture test, just the size of the reaction, defined by 5 mm papule or larger, indicated the hypersensitive person. We consider that this can be taken as the diagnostic criterion and replace in-vitro method for determination of allergen-specific IgE antibodies in serum. Also, overall IgE of serum positively correlated (p < 0.05) with the size of skin reaction only in the persons with extremely high concentrations (RAST class 4) allergen-specific IgE antibodies in serum.

[Significance of monitoring histamine serum levels, cryoglobulins and complement titers during cold tests in patients with cold allergy and Raynaud's phenomenon]. / Znacaj pracenja vrednosti histaminemije, krioglobulina i titra komplementa u toku testa hladjenja u pacijenata sa alergijom na hladnocu i Raynaud fenomenom.

The aim of our investigations is to evaluate blood histamine, complement titer and cryoglobulins before and after cold stimulation (extremity water immersion test) in patients with cold urticaria and Raynaud phenomenon. In our investigations patients were put into five groups according to the following diagnoses: cold urticaria (40 patients), chronic urticaria (15 patients), Urticaria-Vasculitis Syndrome (15 patients), Raynauds Disease (16 patients), and Raynauds phenomenon (15 patients). The investigations demonstrated that the test was always positive in cold urticaria and that a high percentage of patients had a rise in blood histamine. This was found in 50% of the patients while cryoglobulins were found in one third of the patients. Consequently they can be grouped in secondary cold urticarias. A number of patients with chronic urticaria and Urticaria-Vasculitis Syndrome gave a positive history of cold sensitivity. Positive tests were accompanied by a rise in histamine, although (less frequently) there was a decrease in the complement titer and the occurence of cryoglobulins. Raynauds Disease was accompanied by a positive test in 94% of the patients, while patients with Raynauds Phenomenon (whose etiology was Thoracic Outlet Syndrome) had a negative test (60% of the patients). Significant changes were not found in the remaining groups. Positive tests were accompanied by abnormal values of cryoglobulins and of complement titer as well as an increase in histamine. The rise in histamine was not significant in Raynauds Phenomenon, while one patient had a decrease in the complement titer and the appearance of cryoglobulins.

[Atopy and drug allergy]. / Odnos atopije i alergije na lekove.

UNLABELLED: The aim of our study is to show possible correlation between atopy and drug allergy, and the clinical manifestations of drug allergy that may have predictive value. There were 150 patients with positive history of drug allergy, ages 18-73 years. Cutaneous anr/or dose provocative testing was done, depending on the drug. Drug allergy was found in 58 patients (40%). There were 18 patients (12%) with atopic diathesis of which 9 (50%) were found to have drug allergy. Of 17 patients diagnosed as anaphylaxis, 13 (76%) had drug allergy, penicillin being the most common offending drug (7 parients). Of 75 patients diagnosed as urticaria, drug allergy was prouded in 36 (47%) patients. Positive drug allergy was found as follows (percentage wise): trimetoprim-sulfometoksazol 46% (13 tested, 6 positive); penicillin 35,8% (54 tested, 19 positive); noraminophenazone 31% (22 tested, 6 positive); muscle relaxants and general anaesthetics 26% (23 tested, 6 single positive). CONCLUSIONS: Athophy is not predisposing factor for drug allergy; 60% of patients did not have drug allergy although stated in medical documents; anaphylaxis has the highest predictive value, followed by urticardia and fixed drug eruption (when trimetoprim-sulfometoxasol is concerned).

[Effect of ranitidine on the pharmacokinetics of theophylline in patients with obstructive pulmonary disease]. / Moguci uticaj ranitidina na farmakokinetiku teofilina u bolesnika sa opstruktivnim bolestima pluca.

Investigations were performed on 20 patients with mild and moderately severe forms of bronchiale asthma or chronic obstructive bronchitis. Theophylline for oral use (sustained release form) and Ranitidine (second generation H2-blocker) were used in the first group of patients (7 females and 3 males, average age 37.9). Dosage of theophylline from patients sera was monitored at 3, 6 and 12 hours, beginning with the initial morning dose. The second group of patients (9 females and 1 male, average age 46.3) were on Ranitidine therapy, along with 250 mg intravenous theophylline-ethylene-diamine. Fractionated dosage of theophylline was done within 12 hours. Pharmacokinetic parameters were calculated according to the concentration of theophylline in the sera of patients in the second group. Significant differences were not found by statistical analysis (T-test) in the pharmacokinetic parameters of theophylline although significantly higher concentrations of theophylline were found in the sera of patients in the first group. This indicated that there are individual differences on the metabolism of theophylline drugs with concomitant use of Ranitidine.

[Proteinuria in dermal vasculitis (incidence, degree and possible mechanisms of onset)]. / Proteinurija u dermalnim vasculitisima (ucestalost, stepen i moguci mehanizmi nastanka).

The paper comprises 63 patients with diagnosed vasculitis of the skin who had abnormal findings in the urine. Thirteen of these patients had positive skin findings and abnormal findings in the urine, with concomitant attacks of dyspnea as seen in bronchial asthma. These patients account for 20% of the entire group, while there was an incidence of 37% of systemic manifestations. Skin findings: 45% had a maculopapular rash, 36% had urticarial findings, 13% had urticaria and angioedema and 6% had angioedema alone. Nonspecific biologic syndrome of evolution was statistically significant while no significant changes were found in the number of white blood cells and eosinophils. The degree of proteinuria ranged from 0.1 g/L to 1.16 g/L. Most patients with proteinuria above 0.25 g/L had microhematuria. Slightly over 50% of the patients had signs of complement activation by the alternative pathway, along with the presence of cryoglobulins. Increased histamine in the serum was found in over 50% of the patients although the values of histamine did not correlate with the degree of proteinuria. Proteinuria was not detected in patients with very high values of histamine (and without signs of vasculitis), which indicates that histamine itself responsible for changes in the glomeruli. There is a possibility that local tissue hyperhistaminemia is responsible for the increased permeability of the basal membrane of the glomeruli. According to the obtained results, the etiology of proteinuria and microhematuria should be pursued in the pathogenesis of vasculitis as signs of complement activation indicate. Other possible causes for proteinuria were excluded. The proteinuria was selective, benign according to its course and degree, occurred concomitantly with skin findings and was absent during remission of the disease.

[Laboratory study of patients with endemic nephropathy]. / Prilog laboratorijskim ispitivanjima bolesnika sa endemskom nefropatijom.

The introduction deals with the main characteristics of two representatives of high risk pregnancies: diabetes mellitus and EPH gestoses. Particular interest was shown in risks that may occur in pregnant diabetics, with which they must be acquainted. Some theories are given on the pathogenesis of EPH gestoses. The aim of our investigation was to determine the concentration at which immunoglobulins G, M and A pass in cord blood, amniotic fluid and urine, and whether there is a significant difference between control group and among pregnant diabetics or those with EPH gestoses. The investigation was performed by the nephelometric technique on the Immunochemistry Analyzer. Each group consisted of 20 women, with a total of 60. Immunoglobulins A, M and G were determined in the mothers' sera, cord blood or amniotic fluid. IgG was obtained in urine in measurable concentrations. A significant increase of IgG was found in the urine of pregnant diabetics. IgM was significantly increased in the sera of diabetic mothers. IgA was significantly increased in pregnant diabetics, while both high risk pregnancy groups had an increased IgA in cord blood. The values of IgA in amniotic fluid were decreased in the EPH gestoses group in comparison to the group of diabetics. The authors find these variations interesting and feel they should be followed in other high risk pregnancy groups.

[The effect of ranitidine on theophylline pharmacokinetics in patients with obstructive lung disease]. / Uticaj ranitidina na farmakokinetiku teofilina u bolesnika sa opstrukcionim bolestima pluca.

The study was performed in 20 patients with mild and moderately severe forms of bronchial asthma or chronic obstructive bronchitis. Theophylline for oral use (sustained release form) and ranitidine was used in the first group of patients (7 females and 3 males, mean years of age 37.9). Dosage of theophylline from patients' sera was monitored prior and at 3, 6, and 12 hours beginning with the initial morning dose. The second group of patients (9 females and 1 male, mean age 46.3 years) were on ranitidine therapy along with 250 mg intravenous theophylline-ethylene-diamine. Fractionated dosage of theophylline was made within 12 hours. Pharmacokinetic parameters were calculated according to the concentration of theophylline in the sera of patients in the second group. In the sera of patients in the first group significantly higher concentrations of theophylline were found at 3 and 6 hour of the initial morning dose (p less than 0.05). In the second group a significant difference was not registered for the assessed pharmacokinetic parameters. This investigation indicates that there are individual differences of the metabolism of theophylline drugs with concommitant use of ranitidine.