Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema.

BACKGROUND AND OBJECTIVE: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of "vascular preconditioning" predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls. METHODS: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. RESULTS: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 µm), increased apical, internal, and external diameter (28 vs 22 µm; 22 vs 20 µm; and 81 vs 65 µm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. CONCLUSIONS: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema.

Component resolved diagnosis by recombinant allergens in patients with allergies to inhalants.

Molecular characterization of IgE reactivity of specific individual components of allergenic extracts is now possible due to the technology of recombinant allergens derived from studies of molecular biology of allergic pathology. The identification of the immunoreactivity to single allergenic components in allergic subjects allows to specifically define her/his allergic profile and obtain the so-termed Component Resolved Diagnosis (CRD). Molecular allergens can be classified into those that induce the respiratory allergic reactivity and those that identify the food-related allergic pathology. It is also essential to identify those molecular allergens whose immunoreactivity is able to connect the two clinical conditions: respiratory symptoms and food allergy symptoms. The present study was conducted on 50 patients with a clinical history of hypersensitivity to pollen and/or allergy and positivity to Skin Prick Test. The sera were analyzed in our laboratories and the panel of recombinant allergens was applied in the case of positivity of the specific IgE. Of the 50 patients enrolled, 31 were selected as positive to 4 main pan-allergen Bet v1, Par j2, Art v1 and Phl p1; among these, 14 subjects showed one allergen-specific IgE towards natural extracts of tested foods even in absence of clinical history. CRD allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in: a) resolving genuine vs cross-reactive sensitization in poly-sensitized patients, b) assessing, in selected cases, the risk of severe, systemic vs mild, local reactions in food allergy, and c) identifying patients and triggering allergens for specific immunotherapy (ITS). In light of our results, we believe that the transition from a diagnostic based on the use of allergenic extracts to another one based on the use of single allergenic molecules that is able to define the specific allergenic profile of each patient, seems to be able to revolutionize the allergy diagnosis.

Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema: From Bed to Bench.

BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.

Desensitization of two young patients with infantile-onset Pompe disease and severe reactions to alglucosidase alfa.

Pompe disease is a metabolic myopathy, due to deficiency of alpha glucosidase, with a wide clinical spectrum. Enzyme replacement therapy is the only available treatment to improve morbidity and mortality, especially in infantile-onset form. However, some patients experience infusion-associated reactions, which may restrict their access to this treatment. We report on two patients (respectively 12 and 3 months old) with infantile-onset Pompe disease and severe cardiomyopathy, that presented with severe reactions during infusion of enzyme replacement therapy and were successfully desensitized with a new individualized protocol. Our protocol, using microdilution and a premedication with antihistamines, corticosteroids, and tranexamic acid, seems safe and effective and it may allow the continuation of therapy in Pompe patients resulting in the reduction of morbidity and mortality related to this disease.

Pregnancy in women with Hereditary Angioedema due to C1-inhibitor deficiency: Results from the ITACA cohort study on outcome of mothers and children with in utero exposure to plasma-derived C1-inhibitor.

Background: In women with Hereditary Angioedema (HAE) due to C1-inhibitor (C1INH) deficiency (C1INH-HAE), pregnancy counseling and treatment can be challenging. Despite the evidence of the immediate favorable outcome and safety of plasma-derived (pd)C1INH concentrate, there are no data regarding any difference among women who underwent or not pdC1INH during pregnancy or on children with in utero exposure to pdC1INH. The present interview study aimed at analyzing outcome of C1INH-HAE mothers and children according to pdC1INH-exposure during pregnancies. Methods: C1INH-HAE women who experienced at least 1 pregnancy were included from seven centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). The interview study retrospectively analyzed pregnancies who underwent (group 1) or not (group 2) pdC1INH. The overall goals of the study included immediate and long-term outcomes, in terms of outcomes in the time interval between pregnancy and survey. Results: A total of 168 pregnancies from 87 included women were analyzed. At term delivery (>37 gestation-week, GW) has been registered in 73.8% of cases, while spontaneous abortion (SA) occurred in 14.2% of cases with a mean GW 7 ± 2. The group 1 including pdC1INH-treated pregnancies comprised a third of the cohort (51/168, time interval 1.5 ± 10.4 yrs), while the group 2 represented 69.6% (117/168, time interval 32.8 ± 14 yrs). The same prevalence of SA occurred when comparing group 1 (11.7%) with group 2 (15.4%) with a similar GW at SA. The group 1 was older at the pregnancy time and younger at the interview than the group 2 (P < 0.01 for both); moreover, the group 1 showed a higher prevalence of cesarean delivery (P < 0.0001). The overall prevalence of obstetrical syndromes was similar between two groups: however, gestational diabetes was described only in pdC1INH-untreated pregnancies. In utero pdC1INH-exposed children (n = 45) did not show differences compared with unexposed ones (n = 99) in neonatal short-term outcomes. Conclusion: Through appropriate management and counseling, most of C1INH-HAE women undergo successful pregnancy and delivery. For pregnant C1INH-HAE women being treated with pdC1INH, our findings are reassuring and might lead to an improvement of both the knowledge about treatments and the experience of HAE itself.

Immunocompromised patients with HBsAg a determinant mutants: comparison of HBsAg diagnostic assays.

Hepatitis B surface antigen (HBsAg) is considered the best marker for the diagnosis of hepatitis B virus (HBV) infection. Mutations of the s gene involving amino acid substitutions within the a determinant could affect the sensitivity of diagnostic tests. In the present study, HBsAg mutants were detected in 3 immunocompromised patients, previously found to be HBsAg negative and anti-HBs positive. All patients had high levels of HBV-DNA, whereas HBsAg tests gave discordant results. Immunosuppression can cause viral reactivation of occult HBV infection in these patients and favour the selection of HBsAg a determinant mutants.

Thymoma-associated immunodeficiency: a syndrome characterized by severe alterations in NK, T and B-cells and progressive increase in naïve CD8+ T Cells.

Thymomas are rare tumours that sustain T-lymphopoiesis and trigger a variety of autoimmune diseases and immunodeficiencies, including a fatal hypogammaglobulinemia, namely Goods Syndrome (GS). Due to its rarity, GS has been poorly investigated and immunological features, as well as pathogenetic mechanisms underlying this syndrome, are unclear. We studied 30 thymoma patients by performing an immunological assessment, including immunophenotype and analysis of T cell repertoire (TCR). Development of GS was characterized by a progressive decrease in B, CD4 T and NK lymphocytes. These alterations paired with accumulation of CD8+CD45RA+ T cells that showed a polyclonal repertoire without expansions of specific clonotypes. GS is defined as hypogammaglobulinemia with thymoma. Here, we show for the first time that this syndrome is characterized by a severe loss of CD4+, NK and B cells. Furthermore, the accumulation of CD8+CD45RA+ T lymphocytes parallels these changes; this accumulation may have a role in determining the disease and can be used to monitor clinical stages of immunodeficiency in thymoma.

Left ventricular stroke work reserve as prognostic marker in severe heart failure.

AIM: We sought to determine whether an invasive approach based on Swan-Ganz catheterization, coupled with a pharmacologic stressor, might help stratify prognosis in patients with severe heart failure and uniformly depressed indices of cardiac function. METHODS: We studied 31 unselected consecutive patients with scalar doses of dobutamine (2.5-10 microg/kg/min) after baseline hemodynamic evaluation. Changes in stroke work index (SWI) from baseline to peak effect (stroke work reserve, SWR) were recorded, and patients classified as responders (SWR above the median) or non-responders to dobutamine (SWR below the median). One-year follow-up data were recorded. RESULTS: All patients completed the dobutamine challenge test without complications. Dobuta-mine increased SWI from 17+/-9 to 26+/-13 mg/ beat/m2 (P<0.0001 vs baseline), with a median increase of 6.4 g/beat/m2. Basal SWI was not related to stroke work reserve. The only predictor of response to dobutamine was a smaller left ventricular end-diastolic volume (135+/-28 vs 205+/-90 mL/m2; P=0.007). After 1 year, only 7 patients were alive, while 10 had successful transplantation. Transplant-free survival was 47% in responders vs 0% in non responders (P=0.007). At multivariate analysis, none of baseline hemodynamic parameters was predictive of survival. Only age and a SWR above the median were significant independent predictors of survival in this model. CONCLUSIONS: This study allows us to draw the following conclusions: 1) 1-year mortality in severe heart failure remains extremely high; 2) baseline hemodynamics dos not predict survival; 3) a positive response to dobutamine identifies a subgroup with significant lower mortality at 1 year; 4) this response is an independent predictor of survival and is more likely to occur in the presence of a less dilated left ventricle.

Radiation Engineering of Multifunctional Nanogels.

Nanogels combine the favourable properties of hydrogels with those of colloids. They can be soft and conformable, stimuli-responsive and highly permeable, and can expose a large surface with functional groups for conjugation to small and large molecules, and even macromolecules. They are among the very few systems that can be generated and used as aqueous dispersions. Nanogels are emerging materials for targeted drug delivery and bio-imaging, but they have also shown potential for water purification and in catalysis. The possibility of manufacturing nanogels with a simple process and at relatively low cost is a key criterion for their continued development and successful application. This paper highlights the most important structural features of nanogels related to their distinctive properties, and briefly presents the most common manufacturing strategies. It then focuses on synthetic approaches that are based on the irradiation of dilute aqueous polymer solutions using high-energy photons or electron beams. The reactions constituting the basis for nanogel formation and the approaches for controlling particle size and functionality are discussed in the context of a qualitative analysis of the kinetics of the various reactions.

Nailfold Videocapillaroscopy Findings in Bradykinin-Mediated Angioedema

Background: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) and acquired angioedema related to angiotensin-converting enzyme (ACE) inhibitors (ACEI-AAE) are types of bradykinin-mediated angioedema without wheals characterized by recurrent swelling episodes. Recent evidence suggests that a state of “vascular preconditioning” predisposes individuals to attacks, although no data are available on possible structural alterations of the vessels. Objective: This study aims to compare the features of nailfold capillaries to highlight possible structural anomalies between patients affected by C1-INH-HAE and controls and between patients with ACEI-AAE and hypertensive controls.Methods: We used nailfold videocapillaroscopy (NVC) to assess the following: apical, internal, and external diameter; loop length; intercapillary distance; and capillary density, distribution, and morphology. Plasma levels of vascular endothelial growth factor (VEGF) A, VEGF-C, angiopoietin (Ang) 1, and Ang2 were also measured. Results: Compared with healthy controls (n=28), C1-INH-HAE patients (n = 34) were characterized by significant structural alterations of the capillaries, such as greater intercapillary distance (216 vs 190 μm), increased apical, internal, and external diameter (28 vs 22 μm; 22 vs 20 μm; and 81 vs 65 μm, respectively), decreased density (4 vs 5 capillaries/mm2), more irregular capillary distribution, and more tortuous morphology. Apical diameter was enlarged in patients with ≥12 attacks per year. In ACEI-AAE patients, NVC showed no alterations with respect to hypertensive controls. NVC performed in 2 C1-INH-HAE patients during attacks showed no changes compared with the remission phase. Conclusions: We detected major structural capillary alterations in C1-INH-HAE patients, thus confirming the involvement of microcirculation in the pathogenesis of angioedema (AU)

Antecedentes: Tanto el angioedema hereditario con deficiencia de inhibidor del C1 (C1-INH-HAE) como el angioedema adquiridorelacionado con los inhibidores de la ECA (ACEI-AAE), son dos tipos de angioedema mediados por bradicinina que cursan con episodiosde inflamación recurrente sin acompañarse de habones. Existe evidencia de la existencia de un estado de "preacondicionamiento vascular"que predispone a estos pacientes a los ataques, pero no hay datos disponibles sobre las posibles alteraciones estructurales de los vasos.Objetivo: Este estudio tiene como objetivo el evaluar las características de los capilares de la base ungueal para identificar posiblesanomalías estructurales en los pacientes afectados por C1-INH-HAE en comparación con la población sana, y en los pacientes con ACEIAAE en comparación con controles con hipertensión arterial.Métodos: Mediante videocapilaroscopia de la base ungueal (NVC), se evaluaron: los diámetros apical, interno y externo, la longitud delasa, la distancia intercapilar, la densidad capilar, su distribución y su morfología. También se midieron los niveles plasmáticos del factorde crecimiento endotelial vascular (VEGF)-A, VEGF-C, angiopoyetina (Ang)1 y Ang2.Resultados: En los pacientes con C1-INH-HAE (n = 34) se observaron alteraciones estructurales de los capilares significativas, en comparacióncon los controles sanos (n = 28): mayor distancia intercapilar (216 frente a 190 µm), aumento del diámetro apical, interno y externo(28 frente a 22 µm; 22 frente a 20 µm; y 81 frente a 65 µm, respectivamente), disminución de la densidad (4 frente a 5 capilares/mm2),distribución capilar más irregular y una morfología más tortuosa. El diámetro apical fue mayor en aquellos pacientes con ≥12 ataques/año. En los pacientes con ACEI-AAE, las NVC no mostraron alteraciones al ser comparadas con las de los controles hipertensos. Las NVC realizadas en dos pacientes ...(AU)

Angiotensin-converting enzyme inhibitor-associated angioedema: from bed to bench

BACKGROUND: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. OBJECTIVE: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE

ANTECEDENTES: El angioedema asociado al consumo de inhibidores de la enzima convertidora de angiotensina (IECA-AAE) ocurre en el 0,1%-0,7% de los pacientes tratados con IECA. Aunque se sugiere que los ataques de angioedema son el resultado de una mayor permeabilidad vascular, la patogénesis de este proceso no está plenamente esclarecida. OBJETIVO: En este trabajo se estudiaron los parámetros clínicos, genéticos y de laboratorio de pacientes con IECA-AAE, así como el papel de los factores de crecimiento endotelial vascular A y C (VEGF-A y VEGF-C), las angiopoyetinas 1 y 2 (Ang1/Ang2) y la fosfolipasa secretora A2 (sPLA2). MÉTODOS: Se recogieron datos clínicos y de laboratorio de pacientes con IECA-AAE procedentes de dos centros de referencia en angioedema. Se utilizaron pacientes control, que incluyeron a voluntarios sanos y a pacientes tratados con IECA sin angioedema, para comparar las concentraciones de los parámetros de laboratorio. Finalmente, se realizó un análisis genético en un subconjunto de pacientes para detectar mutaciones en los genes SERPING1, ANGPT1, PLG y F12. RESULTADOS: Se diagnosticaron a 51 pacientes (57% hombres) con IECA-AAE. El tiempo promedio para el inicio de los síntomas desde el comienzo del tratamiento con IECA fue de 3 años (rango de 30 días a 20 años). Los lugares más comúnmente afectados fueron: labios (74,5%), lengua (51,9%) y cara (41,2%). El cambio de IECA a ARA-II no se asoció con un mayor riesgo de angioedema en pacientes con antecedentes de IECA-AAE. Los niveles plasmáticos de VEGF-A, VEGF-C y sPLA2 fueron más altos en pacientes con IECA-AAE que en los controles. No se detectaron cambios en las concentraciones de Ang1/Ang2, ni se detectaron mutaciones en los genes analizados. CONCLUSIONES: Nuestros datos sugieren que los ARA-II pueden ser una alternativa terapéutica segura en pacientes con IECA-AAE. El aumento de las concentraciones de VEGF-A, VEGF-C y sPLA2 en pacientes con ACEI-AAE sugiere un posible papel de estos mediadores en la patogénesis de esta enfermedad

Efficacy of subcutaneous immunoglobulins in primary immunodeficiency with Crohn's-like phenotype: report of a case.

Common variable immune deficiency (CVID) is the most frequent primary immunodeficiency in adults. In CVID, the prevalence of gastrointestinal manifestations ranges between 2 and 50% with a complication-related morbidity second only to that of the respiratory tract. In some cases, clinical and endoscopic features are undistinguishable from those of inflammatory bowel disease (IBD). We describe the case of a 28-year-old man in which a diagnosis of Crohn's disease was firstly suspected. Subsequently, a diagnosis of Crohn's-like disease in a patient with CVID was made and a replacement therapy with human normal immunoglobulin intravenously was started. Unfortunately, serum IgG levels remained below 2.0 g/l in pre-infusional controls with persistence of gastrointestinal symptoms and malnutrition despite anti-inflammatory therapy (mesalazine, corticosteroids). Then, the patient began treatment with human normal immunoglobulins administered subcutaneously. The follow-up visits showed a progressive increase in serum IgG. Moreover, the patient reported improvement of gastrointestinal symptoms with reduction of diarrhoea, and laboratory tests showed a progressive and significant improvement. We confirm that therapy with subcutaneously administered immunoglobulins is safe and effective. In addition, our observations indicate that, for patients with CVID and enteropathic complications, replacement therapy with subcutaneous IgG may be the treatment of choice.

Treatment of mastocytosis: pharmacologic basis and current concepts.

Mastocytosis is a rare, heterogeneous disorder characterized by a marked increase in mast cell density in various tissues. Mast cells from different human tissues are heterogeneous. So far, there is no cure for systemic mastocytosis. Conventional therapy is based on agents that antagonize mediators released from mast cells, drugs that inhibit the release of mediators and agents that modulate mast cell proliferation. This pharmacologic approach is satisfactory in the majority of patients with indolent mastocytosis. At the beginning of the new millennium, the therapy of severe forms of aggressive mastocytosis remains a challenge for students of this intriguing disorder.

Cytarabine release from alpha, beta-poly (N-hydroxyethyl)-DL-aspartamide matrices cross-linked through gamma-radiation.

alpha, beta-Poly (N-hydroxyethyl)-DL-aspartamide solutions were cross-linked through gamma-radiation and the systems obtained were tested as matrices for drug sustained release, using cytarabine as model drug. We performed the characterization of the cross-linked polymer, both drug-loaded and unloaded. through water swelling measurements, scanning electron microscopy and X-ray analysis. Finally, we investigated the in vitro release behaviour of cytarabine.

Antiinflammatory effects of oxatomide.

There is increasing evidence that histamine may have wider proinflammatory and immunomodulatory activities than previously reported. It may influence several functions of lymphocytes, monocytes, basophils and macrophages, modulating the release of inflammatory mediators and cytokines. These observations have aroused interest in the pharmacology and clinical applications of histamine H1 receptor antagonists and have led to the identification of novel antiinflammatory properties for this class of drugs. Oxatomide, initially characterized as an H1 antagonist, inhibits the secretion of several mediators of inflammation from human basophils and mast cells. In vitro oxatomide inhibits the release of both preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C4 and prostaglandin D2). The inhibitory effect is not restricted to basophils and mast cells but is also evident on other inflammatory cells such as the neutrophils. In this cell, oxatomide inhibits arachidonic acid mobilization, and leukotriene B4 and platelet-activating factor synthesis, presumably by reducing the activity of cytosolic phospholipase A2. These observations extend the pharmacological activities of oxatomide beyond H1 receptor antagonism and suggest that this drug influences a variety of biochemical events in human inflammatory cells. These antiinflammatory activities help to explain its beneficial effect in various allergic and inflammatory disorders, including urticaria, allergic rhinitis and bronchial asthma.

Abciximab in rescue coronary angioplasty after full-dose tissue-type plasminogen activator.

BACKGROUND: Rescue angioplasty is a complex procedure because of frequent reocclusions secondary to a paradoxical pro-thrombotic effect brought about by thrombolytic therapy. Administration of abciximab may improve procedural results but its utilization in this setting is limited by the potential hemorrhagic risk. Very few data on this approach are currently available in the medical literature. METHODS: After failed full-dose tissue-type plasminogen activator (tPA), 30 patients (23 males, 7 females, mean age 64 +/- 13 years) referred for rescue angioplasty received abciximab (0.25 mg/kg bolus + 0.125 mcg/kg/min x 12 hour infusion) (Abc+ group). The procedural results, hemorrhagic complications and in-hospital outcome observed in these patients were compared to those of 35 patients submitted to rescue angioplasty in the same time period (1997-1999) who did not receive abciximab (Abc- group). RESULTS: In the Abc+ group, 11 patients (37%) were in Killip class 3-4, 14 (47%) had multivessel disease, and 4 (13%) had previous bypass surgery. In all Abc+ patients, factors suggestive of procedural failure were present (i.e. saphenous vein graft occlusion, intraluminal thrombus, dissection, reocclusion, slow flow). The periprocedural heparin dose was 5,000 IU in Abc+ and 100 IU/kg in Abc-patients (range 5,000-10,000 IU). The procedure was successful in 29 Abc+ (97%) and in 34 Abc- patients (97%). A hemoglobin drop > 5 g occurred in 3 Abc+ (10%) and in 4 Abc- patients (11%) with a similar incidence of blood transfusion in the two groups. In all these cases, significant bleeding occurred at the vascular access site. There were 2 in-hospital deaths in Abc+ and 1 in Abc- patients. CONCLUSIONS. Selected patients undergoing rescue angioplasty may be treated with abciximab without an undue increase in hemorrhagic complications. Larger studies are needed to confirm the feasibility of this approach and to assess its potential benefits.

[Biochemical monitoring of the insufficient systemic perfusion in bronchiolitis]. / Monitoraggio biochimico di deficit di perfusione sistemica nella bronchiolite.

Biochemical monitoring was performed on 113 sucklings affected with bronchiolitis in order to evaluate early onset of insufficient systemic perfusion. Values of haematic lactate, GPT and CPK levels in the serum, partial tension of haematic gases were evaluated on first day of hospitalization. Haemogasanalytic monitoring made it possible to differentiate two groups of infants: 21 patients with hypoxemia and 92 patients with normoxemia. Monitoring of lactatemia, CPK and GPT activity evidenced following values: hyperlactemia (66.6%), increased CPK levels (47.6%), increased GPT levels (14.2%) in the group of infants with hypoxemia. Hyperlactemia (55.4%), increased CPK levels (62%), increased GPT levels (19.5%) in the group of patients with normoxemia. These findings show no significant difference between the two groups and frequent occurrence of tissular hypoxia attributable to insufficient systemic perfusion. Moreover the results of such biochemical monitoring permit precise indication about appropriate treatment.

Angiogenesis, lymphangiogenesis and atopic dermatitis.

Angiogenesis and morphological and functional alterations of microvessels are hallmark features of chronic inflammatory disorders, including certain skin diseases. Vascular endothelial growth factors (VEGFs) are key regulators of blood vessel growth. The VEGF family includes VEGF-A, -B, -C, -D and placental growth factor. VEGF-A and -B are the most important proangiogenic factors, while VEGF-C and -D primarily regulate lymphangiogenesis. Angiopoietins are promoters of neovascularization by interacting with Tie-1 and Tie-2 receptors present on endothelial cells. High levels of VEGF-A have been detected in skin tissue of atopic dermatitis (AD) patients and correlate with disease activity. The vascular changes in the skin of AD patients appear to be linked to the inflammatory process. Effector cells of skin inflammation (human mast cells, basophils, eosinophils, macrophages, lymphocytes, etc.) are major sources of a vast array of angiogenic and lymphangiogenic factors. The role of lymphangiogenesis in AD is largely unknown.