Improving long-term adherence to sublingual immunotherapy. Results of a proactive patient-centered management planning.

SUMMARY: Background. Long-term adherence to sublingual immunotherapy (SLIT) results very poor in real-life studies. Effective actions are needed. Key point of any policy aimed to overcoming non-cost related barriers to medication long-term adherence is to actively support patients' needs and preferences starting from shared decisions making. Objective. To explore SLIT related viewpoints, needs and preferences of a homogeneous group of patients. To assess their priority order and to what extent each of them could affect SLIT adherence. To find a rational basis for a proactive action-plan to support patients' needs and preferences and assess results on SLIT long-term adherence. Patients and methods. Preferences and viewpoint of patients in treatment-related decisions and their health-related needs have been explored by structured, direct interview of 65 adult patient. The activities of the hospital outpatient clinic were rearranged to support needs and requests shared by all patients, and to allow tailored interventions integrating them into routine practice. Adherence to SLIT was studied on a different group of 129 patients aged 14 to 42 years and defined as number of patients who completed three years of therapy. Results. SLIT was completed by 98 patients (76%). Main cause of discontinuation for 31 remaining patients have been pregnancy (16%), change of work residence (19%), side-effects (10%), perceived inefficacy (26%), and non-compliance (29%). Conclusions. To improve adherence, it is necessary to investigate patient-related factors to find a common ground to take actions aimed to remove barriers to long-term SLIT-adherence that virtually can work for all patients, but flexible enough to allow patient-tailored interventions. The substantial differences on disease's perception between patients with only allergic rhinitis and those with asthma entail the necessity of differentiated approaches. Management strategy based on shared decision making followed by proactive and ongoing interventions to support patients' needs and preferences proves effective to ensure a good long-term adherence to SLIT in real-life.

Recommendations for the Use of Tryptase in the Diagnosis of Anaphylaxis and Clonal Mastcell Disorders.

Summary: Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the molecular characteristics of the enzyme and its biological effects, the genetic basis of its production and the release kinetics. Recommendations for the clinical use of tryptase measurement developed by a task force of Società Italiana di Patologia Clinica e Medicina di Laboratorio and Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri are given on the best procedure for a correct definition of the reference values in relation to the inter-individual variability and to the correct determination of tryptase in blood and other biological liquids, in the diagnosis of anaphylaxis (from drugs, food, insect sting, or idiophatic), death from anaphylaxis (post mortem assessment) and cutaneous or clonal mastcell disorders.

Anomalous cutaneous absorption of allergens as cause of skin prick testing adverse reactions in adult patients. Clinical and experimental evidence.

BACKGROUND: Paediatric age, active eczema and high number of allergens tested in poly-sensitized patients have been pinpointed as possible risk factors of systemic reactions by skin prick testing. As far as atopic eczema concerns, the higher penetration of the allergens into the skin because of the scraping or micro-injuries is an intuitive rationalization. Purpose of the present study is to provide documentary evidence that adverse reactions elicited by anomalous absorption of allergens can occur also in adult patients with apparently normal skin. METHODS: Report of some exemplifying clinical and experimental observations. Measuring the inoculum volume into impaired skin and its variability in relation to the variation of the chemical-physical characteristic of the solutions used for the tests by means of a method of direct assay based on the use of a gamma-camera. RESULTS: Localized impairments of the skin permeability can cause a significant increase in inoculum volume by prick-test. Critical amounts of allergens can be introduced into the skin because of the possibility of direct absorption, also without pricking, of allergy diagnostic solutions. The greater water content of the solutions used for prick-testing can significantly increase the inoculum volume. CONCLUSIONS: This study adds clinical and experimental evidences that localized impairments of permeability can occur in adult patients with apparently normal skin. Special precautions should be taken when a change of the drops' normal shape and cohesion is seen, because allergy prick-testing in such areas is potentially associated with increased risk of large local or systemic reactions.

Long-term adherence to sublingual therapy: literature review and suggestions for management strategies based on patients' needs and preferences.

Sublingual immunotherapy (SLIT) is an at-home, self-administered, long-term therapy. As with other chronic diseases, patient adherence is a prerequisite for the success of SLIT. Its ease of intake and convenience should ensure adequate patient compliance; however, a recent post-marketing manufacturers' survey has shown a very high rate of discontinuation. The available literature on patient adherence to SLIT is reviewed in the present article. Great differences exist between controlled studies, which show a satisfactory adherence rate, and long-term real-life studies, which show poor compliance with SLIT. Remarkable divergence in the weight placed on different reasons for SLIT discontinuation is reported in the various studies. The main reasons for withdrawal are analysed and discussed. Data from placebo-controlled studies demonstrate that adherence depends less on the patient's perception of the inefficacy of therapy or other causes than on the patient's motivation, that is the patient's decision to participate in the trial and to meet the researcher's expectations. The enrolment of patients who agree to enter a blind, placebo-controlled trial is conceptually similar to a concordance process. Concordance is a consultation process that aims to establish a therapeutic alliance between the physician and patient and to bring about agreement on a therapeutic programme. Concordance is based on the patient's beliefs and needs and implies actions that support the patient's adherence. Suggestions are given for a SLIT management strategy based on the concordance process and designed to integrate the patient's viewpoints into treatment-related decisions and to meet patients' preferences and their health-system-related needs.

Risk assessment of immediate systemic reactions from skin tests with ß-lactam antibiotics.

BACKGROUND: Some clinical studies have demonstrated that skin tests for ß-lactam antibiotics may cause more adverse reactions than skin tests for common allergens. OBJECTIVE: To assess the risk of systemic reactions from penicillin skin testing, based on a pre-test categorization of patients, in order to establish an appropriate strategy for preempting and dealing with cases. METHODS: A case series of 175 patients with a suspected allergy to penicillin was reviewed, and patients were classified as having a low or high probability of allergic sensitization to penicillin, according to their clinical history. For every group, the rate and the increase in the relative risk (RRI) of systemic reactions by skin testing were calculated. The results were compared to those reported in the available literature. RESULTS: In our case series of 175 patients, 52 were classified as having a high probability of being allergic to penicillin, according to their clinical history. Five systemic reactions to skin testing were observed, and these were exclusively in this group (9.61%, RRI = 479). In agreement with the literature, patients with a high likelihood of penicillin allergy showed an increase of up to 10% in the occurrence of systemic reactions at skin testing; in patients who had had severe allergic reactions, this figure was up to 20%. CONCLUSIONS: The RRI of systemic reactions by skin testing is proportional to the pre-test probability of a true immediate hypersensitivity reaction to ß-lactam antibiotics. In the present case series, only patients with high pre-test probability were at risk, and this group should therefore be skin tested and monitored in a hospitalization regimen, where resuscitation staff and access to an emergency room are immediately available.

Food-specific IgG4 lack diagnostic value in adult patients with chronic urticaria and other suspected allergy skin symptoms.

BACKGROUND: Specific IgG4 dosing against food is proposed to the public by a lot of commercial laboratories as a reliable method to diagnose food intolerance. Actually, few data on IgG4 responses to foods in adults are available in the literature. In this study we evaluated the clinical utility of specific IgG4 dosing against food in adult patients with suspected food allergy/intolerance. METHODS: A case series of 73 adult patients with suspected food allergy and clinical manifestations of chronic urticaria or other allergy-supposed skin symptoms were tested for specific IgG4 against foods. An open food challenge was carried out for all IgG4-positive food. All positive open tests were controlled by double-blind placebo-controlled food challenge. RESULTS: Forty-five patients (62%) were IgG4 positive for a number of foods, mainly egg, milk, casein and wheat. None of the patients with IgG4-positive testing showed adverse reactions, neither immediate nor delayed, to the corresponding food. CONCLUSIONS: In adult patients, testing for specific IgG4 lacks clinical utility for the diagnosis of food allergy or intolerance. Dosing of IgG4 should not be part of the diagnosis and therapy of adult patients with allergy-like skin diseases.

Diagnosing systemic lupus erythematosus: new-generation immunoassays for measurement of anti-dsDNA antibodies are an effective alternative to the Farr technique and the Crithidia luciliae immunofluorescence test.

The aim of this study was to evaluate the diagnostic performance of four new enzyme immunoassays (EIAs) for anti-double-stranded-DNA (anti-dsDNA) antibodies, in comparison with the Farr assay and the Crithidia luciliae immunofluorescence test (CLIFT). To this purpose, sera from four patient groups were collected: 52 sera from patients with systemic lupus erythematosus (SLE); 28 from patients with other connective tissue diseases (CTD); 36 from patients with hepatitis C virus (HCV) infection; and 24 from those with acute viral infection. All sera were tested for anti-dsDNA antibodies by four EIA methods using a different antigenic DNA source [synthetic oligonucleotide (Method A), circular plasmid (Method B), recombinant (Method C), and purified extracted (Method D)], and by CLIFT and Farr assays. The diagnostic sensitivity of the assays was as follows: 84.6% (Method A), 73% (B), 82.7% (C), 84.6% (D), 55.8% (CLIFT), and 78.8% (Farr). Specificity was 82.9% (A), 97.7% (B), 96.5% (C), 94.3% (D), 96.5% (CLIFT), and 90.9% (Farr). From these data, we can conclude that the new-generation EIA methods evaluated in this study have higher sensitivity than the CLIFT and Farr assays and, with the exception of Method A, have specificity similar to the CLIFT and slightly higher than the Farr assay. These findings suggest that EIA tests may replace CLIFT as a screening test and the Farr assay as a specific test, for anti-dsDNA antibody detection.

Diagnostic accuracy of different immunological methods for the detection of antineuronal antibodies in paraneoplastic neurological syndromes.

The aim of this work was to evaluate the diagnostic accuracy of three different analytical methods for the detection of antineuronal antibodies and outline how they might be used to diagnose Paraneoplastic Neurological Syndromes (PNS) in a more effectively and rationally way. One hundred and four patients with neurological diseases were studied: 38 with paraneoplastic neurological disorder, 44 with other neurological diseases, and 22 with systemic autoimmune diseases and neurological disorders. 20 healthy subjects and 18 subjects with tumour without neurological disorders were also studied. Antineuronal antibodies were tested using three methods: Western blot (WB); Line-blot (LB); and indirect immunofluorescence (IIF) on primate cerebellum. The diagnostic sensitivity of the IIF, WB and LB methods was 28.9%, 26.3% and 36.8%, respectively, and their specificity was 95.2%, 97.1% and 98.1% respectively. The combined use of the three methods brought the sensitivity to 39.4%. The results of this study show that the methods used in clinical laboratories for the detection of antineuronal antibodies have good specificity. Among the three methods assessed, LB showed the highest diagnostic accuracy and also allowed for recognition of fine antibody specificities. According to these results we can suggest that LB should be used as the method of choice to search for paraneoplastic antibodies.

Long-term tolerability of etoricoxib in different types of NSAID-intolerant subjects.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are a frequent cause of hypersensitivity reactions, therefore, in clinical practice, it's important to find safe and effective substances. OBJECTIVE: To evaluate the tolerability of etoricoxib and its subsequent actual use and safety at home. METHODS: Etoricoxib tolerance was assessed by single-blind-placebo-controlled oral challenges and its subsequent use was checked by a standardized telephone call. The test was performed in 139 subjects (83 single NSAID reactors and 56 multiple NSAID reactors). RESULTS: The drug was not tolerated in 4 cases (2.8%) causing wheals on the face area in 3 single reactors and a severe generalised reaction occurring three hours after the intake of a therapeutic dose in a multiple reactor. The phone calls showed that 64 (52.8%) patients did not take etoricoxib, mostly due to the fear of adverse effects; in 5 cases (4.2%), the practitioner prescribed a different NSAIDs. Only 52 (43%) subjects took etoricoxib after oral challenges; all tolerated the drug but 2 single reactors, who reported a very mild labial oedema. CONCLUSION: Our study confirmed the good long-term tolerability of etoricoxib in patients with a history of hypersensitivity to other NSAIDs without differences between single and multiple reactors. Nonetheless, in NSAID-intolerant subjects this drug should be first challenged in specialised centres due to the risk ofsevere reactions.

How much specific is the association between hymenoptera venom allergy and mastocytosis?

BACKGROUND: The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs. METHODS: Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations. RESULTS: A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder. CONCLUSION: The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.

Comparison of different diagnostic products for skin prick testing.

BACKGROUND: Different in vivo methods are used to quantify the amount of allergens in products for skin prick testing. It is unclear how this impacts on the correct diagnosis of allergies. AIM OF THE STUDY: We compared the allergenic potency of three commercial extracts for skin prick testing and evaluated batch-to-batch differences within each product. METHODS: Patients with a mono-sensitization (specific IgE level > 0,70 KU/L, ImmunoCAP, Phadia) to Phleum pratense (N=21), Parietaria judaica (N=20) or Dermatophagoides pteronyssinus (N=28) were evaluated by standard skin prick testing and with the end-point dilution technique using commercial products from Stallergenes (A) (Antony, France), Lofarma Allergeni (B) (Milan, Italy) and ALK Abellò (C) (Hoersholm, Denmark). Results were expressed as mean areas of the wheal (cut-off for positive reactions: 7 mm2). RESULTS: With standard prick testing, the following differences in wheal areas were found: Phleum, C higher than B (p=0.0454); Parietaria, C higher than A (p=0.094); Dermatophagoides, C higher than A (p=0.021). With limiting dilution testing, the following differences in dilutions yielding positive skin prick tests were found: Phleum, C and B higher than A (p=0.0391 and 0.0039, respectively); Dermatophagoides, C higher than A and B (p=0.0010 and 0.0156, respectively). In the batch-to-batch comparison, mean differences between wheal areas of compared undiluted solutions did not significantly differ in any allergen tested, although in single cases large differences were observed. At the 1 to 64 dilution, agreement was significant only with Dermatophagoides from Manufacturer C (p= 0.262). At the 1 to 16 dilution, agreement was significant with Phleum from Manufacturer C (p=0.0116) and with Dermatophagoides from Manufacturer B and C (p=0.0239 and 0.0001, respectively). At the 1 to 4 dilution agreement was significant with Dermatophagoides from the three considered Manufacturers (p=0.0189, 0.0052 and 0.0077, respectively) and with Phleum from Manufacturer B and C (p=0.0336 and 0.0113, respectively). CONCLUSION: There are significant differences among commercially available diagnostic products for skin prick testing.

Standardization of skin tests for diagnosis and prevention of hypersensitivity reactions to oxaliplatin.

BACKGROUND: Platinum salts can cause allergic sensitization. Recently, hypersensitivity reactions to oxaliplatin, the most recent platinum coordination complex introduced into clinical practice, have been reported. OBJECTIVE: To validate and standardize skin tests to diagnose and possibly prevent hypersensitivity reactions to oxaliplatin. The secondary aims were to confirm IgE-mediated pathogenesis of the clinical manifestations and to evaluate skin tests to predict patients at risk of hypersensitivity reactions to oxaliplatin. METHODS: We performed skin tests at increasing concentrations of oxaliplatin on 15 patients never exposed to platinum salts, on 10 patients treated with oxaliplatin without any adverse reactions, and on 4 patients who had shown hypersensitivity reactions to the drug. Moreover we performed skin tests on 8 additional patients starting before the 5th dose and following a course of chemotherapy. RESULTS: A positive skin reaction to the prick test at a concentration of 1 mg/ml was seen in 1 patient with hypersensitivity reactions. The intradermal test was positive in all the patients with hypersensitivity reactions at a concentration of 0.1 mg/ml. It was negative in the 15 nonexposed subjects, and in the 10 patients who had been exposed to oxaliplatin without hypersensitivity reactions. The skin test administered to patients before chemotherapy was positive in one case. CONCLUSION: A skin prick test at a concentration of 1 mg/ml and, in the case of a negative response, an intradermal test at the optimal concentration of 0.1 mg/ml should be used, starting from the 5th course of therapy, to diagnose and prevent hypersensitivity reactions to oxaliplatin.

Ankle brachial pressure index usefulness as predictor factor for coronary heart disease in diabetic patients.

Ankle brachial pressure index (ABPI) is a non-invasive marker of atherosclerosis, helpful to identify subjects at high-risk for coronary heart disease (CHD) among large populations with cardiovascular disease (CVD) risk factors. The diagnostic role of ABPI has been also recognized in patients with diabetes. In the present study, the role of an ABPI score < 0.90 in predicting CHD has been evaluated in a large series of patients with Type 2 diabetes mellitus and compared to other known CVD risk factors. Nine hundred and sixty-nine (mean age was 66.1 yr) consecutive patients with Type 2 diabetes mellitus were evaluated. The patients were followed-up for 18.3+/-5.2 months (range 12- 24) and all events of CHD, defined as myocardial infarction, unstable and resting angina or coronary atherosclerosis at the instrumental investigation (at the coronary angiography and/or perfusion stress testing) were recorded. A rate of 17.5% of CHD events were recorded in diabetic population during the follow-up period. The relative risk of CHD was significantly increased for male patients [odds ratio (OR): 1.6; 95% confidence interval (CI): 1.1-2.2], patients with age > or = 66 yr (OR: 1.8; 95% CI: 1.3-2.5), body mass index (BMI) > 30 (OR: 1.5; 95% CI: 1.1-2.1), waist circumference > 88 cm for females and 102 cm for males (OR: 1.5; 95% CI: 1.0-2.1), proteinuria > or = 30 microg per min (OR: 1.6; 95% CI: 1.1-2.3), LDL-cholesterol > or = 100 mg/dl (OR: 2.1; 95% CI: 1.5-3.0), glycated hemoglobin > 7% (OR: 1.6; 95% CI: 1.1-2.3), insulin therapy (OR: 1.9; 95% CI: 1.3-2.9), and ABPI < 0.90 (OR: 3.7; 95% CI: 2.2- 6.2). BMI was higher in patients with ABPI < 0.90 than in those with ABPI > or = 0.90 (p<0.05). At the multivariate analysis, ABPI < 0.90 was the best factor independently associated with CHD (p<0.001). APBI < 0.90 is strongly associated to CHD in Type 2 diabetic patients. We recommend to use ABPI in diabetic patients and to carefully monitor diabetic subjects with an ABPI lower than 0.90.

Priming-like effect and successful desensitization after anaphylactic shock by latex sublingual immunotherapy.

The present report deals with some unusual events observed restarting allergy vaccine in a case of anaphylactic shock which occurred giving the maximum scheduled dose (25 drops) of rush sublingual immunotherapy (SLIT) to latex. Restarting SLIT by usual (not rush) scheme we observed long-lasting fall of reactivity threshold. The maximum tolerable dose was reduced to 2 drops, a dose fivefold smaller than the one well tolerated during previous rush phase (10 drops). We have excluded a possible nocebo effect and proved that the reduced tolerance was real by double blind placebo-controlled challenge test. We have considered this effect in some ways similar to priming effect. SLIT was continued with two drops every day. After about twenty months we could demostrate a significant reduction of skin reactivity by end-point technique and an improved response to the controlled exposition to latex by use-tests. In the same time the tolerance to vaccine was improved to three drops. The better safety profile allowed us to restart and continue with SLIT also in the reported case of anaphlicatic shock by latex vaccine and, after about two years, to induce valuable hyposensitization. Latex SLIT is confirmed as a safe and effective method.

A prospective study of 1038 pregnancies on the predictive value of anti-annexin V antibodies for fetal loss.

Retrospective studies have demonstrated that anti-annexin V (anti-AnxV) antibodies are linked to miscarriage. Their predictive value is, however, unknown. We have carried out a prospective study to evaluate the relationship between anti-AnxV antibodies and the pregnancy outcome. A serum sample was taken from 1038 consecutive healthy women at the beginning of pregnancy. IgG and IgM anti-AnxV antibodies were measured by an ELISA method. The cutoff value was set at 5 units for both IgG and IgM. Out of 1038 women, 116 (11.4%) had a miscarriage by the 22nd week; 10 were lost to follow-up, 10 had an induced abortion, 6 had a preterm delivery, and 896 carried their pregnancy through to term. An adverse outcome of the pregnancy proved to be directly related to the number of previous miscarriages (P = .008) and the age of the woman (P = .002). IgG and IgM anti-AnxV were present in 25% and 27% of the women who miscarried, and in 23% and 28% of those who gave birth (mean antibody concentration IgG, 4.2 vs. 4.4 U/mL; IgM, 3.7 vs. 3.5 U/mL). IgG and IgM anticardiolipin and anti-beta(2)GPI, together with antinuclear, antithyroperoxidase, and antithyroglobulin antibodies, were also measured in the 116 sera of the women with miscarriage and in an equal number of women who gave birth. Their positivity or level proved not to be useful in discriminating between the risk of miscarriage and term delivery. This large-scale prospective study demonstrates that the presence of IgG and IgM anti-AnxV antibodies, when measured in healthy women, does not give a positive predictive lead towards the possibility of a miscarriage, and it is not useful in evaluating the risk of miscarriage at the beginning of pregnancy.

Accuracy of semiquantitative immunoenzymatic methods in quantitation of anti-topoisomerase I (Scl-70) antibodies.

Reports of a possible correlation between anti-Scl-70 antibody concentration and clinical manifestations in systemic sclerosis patients have recently appeared in the scientific literature. The goal of our study was to evaluate, by means of a multicenter study, the analytical reliability of immunoassay systems in the quantitative measurement of Scl-70 antibodies. Three blind samples (H, M, L) at different anti-Scl-70 antibody concentrations, and a low concentration antibody serum (LPC) used as a common calibrator, were sent three times in a 6-month time span to 39 Italian clinical laboratories. Each laboratory was asked to calculate dosages following the enzyme-linked immunosorbent assay (ELISA) method they used and report the optical density values of each sample (ODs), of the cutoff serum provided by the manufacturer of the kit used (ODco) and of LPC (ODLPC). The overall analytical imprecision (between methods and between laboratories) of the three different determinations of the values respectively expressed in ODs, ODs/ODco and ODs/ODLPCratio was 47.1, 52.8 and 34.0% for sample H, 56.2, 47.4% and 34% for sample M and 84.6, 86.0 and 86.6% for sample L. The average intra-method analytical imprecision was, respectively, 20.7, 29.8 and 18.6% for sample H, 24.6, 26.5 and 19.3% for sample M, and 30.6, 28.1 and 20.2% for sample L. The commercial ELISA methods currently used to determine the presence of anti-Scl-70 autoantibodies show considerable differences in the quantitative determination. The best results for reproducibility analyses have been obtained when the values were expressed as a ratio between the ODs of the sample and of the common calibrator (ODs/ODLPC). Forward-looking clinical studies that can clarify the usefulness of quantitative determination of anti-Scl-70 antibodies in the monitoring of diffuse scleroderma patients can be performed only when standard serum with a known antibody concentration and calibration curves for quantitative ELISA measurements are made available.

Cysteine-induced enhancement of lipid peroxidation in substantia nigra: comparative effect with exogenous administration of reduced glutathione.

It is generally accepted that reactive oxygen species have a major role in the mediation of cell damage and that free sulphydryl (SH) groups are vital in cellular defence against endogenous or exogenous oxidants. Modification of cellular oxidant/antioxidant balance has been involved in the neuropathogenesis of several diseases, e.g., stroke, Parkinson's disease, Alzheimer's disease and physiological ageing. An increasingly important area of antioxidant defence is based on sulphydryl chemistry, owing to the role of SH groups in the function of macromolecular structures such as enzymes and cellular membranes. Thiols, however, may themselves generate deleterious free radicals, and thionyl radicals, which have been demonstrated to originate in biological systems through enzymatic reactions of different peroxidases, by reacting with molecular oxygen or hydrogen peroxide are able to promote reactions of oxidatives stress. In the present study we provide experimental evidence suggesting a selective effect of cysteine in promoting reactions of oxidative stress in the brain areas of substantia nigra and septum, but not in other areas. In contrast, exogenous administration of reduced glutathione led to a significant decrease of lipoperoxidation in the brain areas of cortex and hippocampus, associated to selective changes in the endogenous pool of thiols.

Morphometry in skin-test methodological studies--validation of the point-counting technique for precise area determination.

BACKGROUND: The methods for delimiting and measuring cutaneous responses can significantly influence the result of skin tests. For this reason, when skin tests are used for purposes of clinical research, the use of computerized methods is recommended to reduce the measurement error of traditional methods. In the present study we evaluated the degree of precision and accuracy of the point counting technique, employed in morphometry for measuring plane images. METHODS: The degree of precision and accuracy of the point counting technique were studied using a panel of geometric figures (circles and ellipses) of scalar size and some series of wheals and flares of various sizes, from very small dimensions to greater and irregularly-shaped ones, which can represent the different degrees of intensity of cutaneous responses. The efficiency of the method was compared with the efficiency of the traditional one based on the measurement of diameters. RESULTS: Under the various experimental conditions the average measurement error by the point counting technique was contained within the limit of 8%, with a variation coefficient of about 7%. Unlike the traditional method based on the length of diameters, the point counting technique proves to be very precise and accurate to estimate both areas of small dimensions and very large and irregularly-shaped ones. CONCLUSIONS: The point counting method proved to be reliable and to possess a satisfactory degree of accuracy and precision in the measurement of cutaneous responses of any type. When computerized programmes are not available, the point counting technique can advantageously be used for purposes of clinical research and for methodological studies on prick test procedures.

[Modifications induced on thrombin and plasmin activity by voluntary interruption of pregnancy]. / Modificazioni indotte dall'interruzione volontaria di gravidanza sull'attivazione trombinica e plasminica.

Pregnancy is characterized by plasmatic variations of coagulative factors' concentration and by different haemostatic-fibrinolytic balance. At present it is possible, with EIA methods, to measure fibrinogen (FgDP) and fibrin (FbDP) degradation products with precision and accuracy, as direct indexes of fibrinolysis and the thrombin-antithrombin III complex (TAT) as indirect index of thrombophilia. We have considered the course of those indexes in 61 pregnant women within the tenth week of gestation, before and after voluntary pregnancy interruption (VPI) resulted without complications. The results don't show any peculiar variation of the examined parameters between the pregnant women before VPI and a control group. Comparing the basal data with those obtained three hours after VPI, all indexes are increased, particularly FbDP. After 24 hours the concentration of FgDP, FbDP and TDP decreased in comparison with the three hours control drawing, nevertheless staying higher than the values obtained in the basal drawing. The evolution of FDP and of TAT, in our study, points out that, in the first weeks of pregnancy, the haemostatic-fibrinolytic balance does not differ significantly from the physiological balance. Three hours after VPI fibrinolytic mechanisms prevail as regards the fibrinogenolytic ones. TAT increases after 3 hours and returns to the rules after 24 hours, proposing itself as an indirect index of thrombinic activation and as a direct index of antithrombinic activity.

[What is the best treatment in massive pulmonary embolism: anticoagulants, thrombolytics or surgical embolectomy?]. / Quale trattamento per l'embolia polmonare massiva: gli anticoagulanti, i trombolitici o l'embolectomia chirurgica?

The aim of this work was to identify the best treatment available for massive pulmonary thromboembolism which still remains a frequent and sometimes lethal complication for surgical and non-surgical patients. The Authors underline the difficulties of diagnosis and the need for therapy at the earliest possible stage. At present, clinical management involves the use of: anticoagulants, thrombolytic agents and surgical embolectomy. In conclusion, the authors state that pulmonary thromboembolism, even when massive, has been transformed into a medically interesting pathology which can be cured using heparin and thrombolytic agents. However, surgical treatment is mandatory when patients reveal adverse effects to drug therapy, when medical therapy is insuccessful, or when patients are seriously ill with recurrent cardiac arrest.