Barnacle Allergy: Allergen Characterization and Cross-Reactivity with Mites

Background: Barnacles are a type of seafood with worldwide distribution and abundant along the shores of temperate seas. They are particularly appreciated and regularly consumed in Portugal as well as in Spain, France and South America, but barnacle allergy is a rare condition of which there is only one reference in the indexed literature. The molecular allergens and possible cross-reactivity phenomena implicated (namely with mites) have not been established. Objective: To demonstrate the IgE-mediated allergy to barnacle and to identify the proteins implicated as well as possible cross-reactivity phenomena with mites. Methods: We report the clinical and laboratory data of five patients with documented IgE-mediated allergy to barnacle. The diagnosis was based on a suggestive clinical history combined with positive skin prick tests (SPT) to barnacle – prick to prick method. Two barnacle extracts were prepared (raw and cooked barnacle) and sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and IgE-immunoblotting were performed. An immunoblotting inhibition assay with Dermatophagoides pteronyssinus was also done in order to evaluate cross-reactivity. Results: All patients had mite-related asthma and the allergic rhinoconjunctivitis; they all experienced mucocutaneous symptoms. All of them had positive SPT to barnacle, and the immunoblotting showed several allergenic fractions with a wide molecular weight range (19 – 94 kDa). The D. pteronyssinus extract inhibited several IgE-binding protein fractions in the barnacle extract. Conclusions: We describe five patients with IgE-mediated barnacle allergy. We also describe a group of IgEbinding+ proteins between 30 and 75 kDa as the allergenic fractions of this type of Crustacea. Cross-reactivity with D. pteronyssinus was demonstrated in two cases.

Candidemia in Acute Leukemia Patients

Fungal infections are an important cause of morbidity and mortality in patients with acute leukemia (AL). Candidemia, once rare, is now a common nosocomial infection because of the intensity of chemotherapy, prolonged neutropenia, administration of broad-spectrum antibiotics and use of central venous catheters (CVC). We retrospectively identified patients treated for AL from 6/86 to 6/95 who also had candidemia. We describe 28 patients (incidence 6.3%) with a median age of 39 years, 24 of whom were on remission induction and 4 on postremission chemotherapy. All patients had CVC and empiric antimicrobial therapy, 4 had been given prophylactic antifungal drugs, and 2 had parenteral nutrition. Neutropenia was profound (median leukocyte nadir 200/microliters, median duration 19 days). Candida was isolated in blood cultures 10 days (median) after the start of neutropenia. The clinical presentation included fever (100%), respiratory symptoms (71.4%), skin lesions (39.2%) and septic shock (17.8%). Amphotericin B was given to 17 patients and liposomal amphotericin to 5 patients. Infection resolved in 18 patients (64.2%). 10 of whom were in complete remission. Mortality from candidemia was 17.8% (5/28). In conclusion, fungal infections are responsible for death in a significant number of patients. In our series treatment success was related to its rapid onset and to the recovery of neutropenia.

Sirolimus-Induced Drug Fever in a Renal Transplant Patient: a Case Report

Herein we have described the case of a male renal transplant recipient who developed drug fever apparently related to sirolimus. He had been stable under an immunosuppressive regimen of tacrolimus and mycophenolate mofetil, but developed acute cellular rejection at 5 years after transplantation due to noncompliance. Renal biopsy showed marked interstitial fibrosis, and immunosuppression was switched from mycophenolate to sirolimus, maintaining low tacrolimus levels. One month later he was admitted to our hospital for investigation of intermittently high fever, fatigue, myalgias, and diarrhea. Physical examination was unremarkable and drug levels were not increased. Lactic dehydrogenase and C-reactive protein were increased. The blood cell count and chest radiographic findings were normal. After extensive cultures, he was started on broad-spectrum antibiotics. Inflammatory markers and fever worsened, but diarrhea resolved. All serologic and imaging tests excluded infection, immune-mediated diseases, and malignancy. After 12 days antibiotics were stopped as no clinical improvement was achieved. Drug fever was suspected; sirolimus was replaced by mycophenolate mofetil. Fever and other symptoms disappeared after 24 hours; inflammatory markers normalized in a few days. After 1 month the patient was in good health with stable renal function. Although infrequent, the recognition of drug fever as a potential side effect of sirolimus may avoid unnecessary invasive diagnostic procedures. Nevertheless, exclusion of other common causes of fever is essential.

Renal Pathology in Portuguese HIV-Infected Patients

HIV-infected patients may be affected by a variety of renal disorders. Portugal has a high incidence of HIV2 infection and a low prevalence of HIV-infected patients under dialysis treatment. The aim of this study was to characterise the type of renal disease in Portuguese HIV-infected patients and to determine if HIV2 infection is associated to renal pathology. Only 60 of the 5158 HIV-infected patients followed in our hospital underwent renal biopsy. Clinical and laboratory data and the type of renal disease were reviewed. Male gender was predominant (76.7%), as was Caucasian race (78.3%). Mean age was 37.9±10.6 years. The majority had criteria for AIDS, 66% were on combined antiretroviral therapy and 18.3% were on dialysis. The predominant lesions were immunecomplex glomerulonephritis (n=19), tubulointerstitial nephropathy (n=12), focal segmental glomerulosclerosis(n=11), followed by HIVAN (n=8). Other patterns(amyloidosis, vasculitis, minimal change lesion) were observed. Only three patients were HIV2 infected, and presented diabetic nephropathy, acute tubular necrosis and tubulointerstitial nephritis. No correlations between clinical findings and renal pathology were found. In conclusion, renal disease in HIV patients has a broad spectrum, and renal biopsy remains the gold standard for establishing the diagnosis and guide treatment. Renal disease is not frequent in HIV2-infected patients, and, when present, is probably not directly associated with HIV infection.

Environment and Health in Children Day Care Centres (ENVIRH) - Study Rationale and Protocol

Background: Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. Methods --- study design: This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children’s respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. Results: In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children’s health. A building ventilation model will also be developed. Discussion: This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC.

A Rare Abdomino-Pelvic Tumor: Paraganglioma

Paragangliomas are rare tumors, with a reported incidence of 2–8 per million. They are chromaffin cell tumors that develop from the neural crest cells and may be divided in tumors derived from the parasympathetic or sympathetic ganglia. We report a case a of a 32-year-old nulliparous woman, referred to our Infertility Clinic. Abdomino-pelvic ultrasound identified a large abdominopelvic tumor, without ovarian origin (both ovaries were identified and had normal morphology). Magnetic Resonance Imaging suggested a right adnexal multicystic, vascularized mass close to iliac vessels and questioning an ovarian origin. At exploratory laparotomy, a 10 cm encapsulated and vascularized mass was found beginning just below right renal artery and extending to the level of the broad ligament. This mass was totally excised and histopathology was consistent with Paraganglioma.

Efeito Conjunto da Exposição à Poluição do Ar e aos Ácaros do Pó Sobre as Vias Aéreas

Introdução: A asma é uma doença respiratória crónica, cujo agravamento pode estar associado a factores ambientais, entre os quais os relacionados com a qualidade do ar. Objectivo: O presente trabalho pretendeu avaliar o efeito da exposição individual a poluentes atmosféricos em termos de função respiratória, num grupo de crianças com história de sibilância, entrando em consideração com o grau de infestação de ácaros do pó doméstico. Métodos: Um grupo de 51 crianças com história de sibilância, seleccionadas através do questionário do estudo ISAAC, foi acompanhado prospectivamente num estudo com medidas repetidas, que envolveu avaliações médicas padronizadas que incluíram a realização de espirometria, avaliação da exposição aos ácaros do pó e cálculo do valor de exposição individual a uma variedade de poluentes do ar: PM10, O3, NO2, benzeno, tolueno, xileno, etilbenzeno e formaldeído. Resultados: Observou -se uma elevada percentagem de colchões com um grau de infestação de ácaros médio ou elevado. Com excepção dos valores de PM10, os valores de exposição aos poluentes do ar não alcançaram valores elevados. Na análise multivariável, tanto os poluentes (designadamente PM10, NO2, benzeno, tolueno e etilbenzeno) como o grau de infestação de ácaros do pó associaram -se a deterioração da função pulmonar. Conclusão: O presente trabalho vem reforçar o interesse da exposição aos poluentes do ar em crianças com história de sibilância, que à semelhança do que acontece com os ácaros do pó influenciam as vias aéreas.

Bronchial Asthma in Children: Clinical and Epidemiologic Approach in Different Portuguese Speaking Countries

BACKGROUND: Geographical differences in asthma prevalence are currently accepted, but evidence is sparse due to the lack of multicentre studies using the same protocol. OBJECTIVES: To compare the prevalence of asthma and atopy among schoolchildren from Portuguese speaking countries (ISAAC and Portuguese Study) and evaluate some environmental variables, such as house dust mite exposure. MATERIAL AND METHODS: Significant random samples of schoolchildren studied with standard validated methods--questionnaires, skin prick tests, methacholine bronchial challenge tests; dust bed sampling for analysis of mite antigens. RESULTS: In the ISAAC study, in the 13-14 year-old age group, statistical significant differences were found, with higher wheezing prevalence in Brazil than in Portugal (two-fold). In the Portuguese Study, atopy prevalence ranged between 6.0 and 11.9% in Sal and S. Vicente (Cape Verde), up to 48.6 and 54.1% in Macau and Madeira. Active asthma had the higher values in Madeira (14.6%), and the lower in Macau (1.3%). Cape Verde had intermediate asthma prevalence (10.6 and 7.0%). The bronchial challenge test was positive in 25, 66 and 70% of asthmatic children from Sal, S. Vicente and Madeira respectively. Significant HDM antigen concentrations (Der p1) were found in Cape Verde and Madeira. CONCLUSIONS: There are significant variations in asthma and atopy prevalence between these pediatric populations. The reasons remain under discussion, but genetics linked to race, seem to play a central role, modulated by environmental and lifestyle variables.

Nursing Home-Acquired Pneumonia Presenting at the Emergency Department

Nursing home-acquired pneumonia (NHAP) is one of the most common infections arising amongst nursing home residents, and its incidence is expected to increase as population ages. The NHAP recommendation for empiric broad-spectrum antibiotic therapy, arising from the concept of healthcare-associated pneumonia, has been challenged by recent studies reporting low rates of multidrug-resistant (MDR) bacteria. This single center study analyzes the results of NHAP patients admitted through the Emergency Department (ED) at a tertiary center during the year 2010. There were 116 cases, male gender corresponded to 34.5 % of patients and median age was 84 years old (IQR 77-90). Comorbidities were present in 69.8 % of cases and 48.3 % of patients had used healthcare services during the previous 90 days. In-hospital mortality rate was 46.6 % and median length-of-stay was 9 days. Severity assessment at the Emergency Department provided CURB65 index score and respective mortality (%) results: zero: n = 0; one: n = 7 (0 %); two: n = 18 (38.9 %); three: n = 26 (38.5 %); four: n = 30 (53.3 %); and five; n = 22 (68.2 %); and sepsis n = 50 (34.0 %), severe sepsis n = 43 (48.8 %) and septic shock n = 22 (72.7 %). Significant risk factors for in-hospital mortality in multivariate analysis were polypnea (p = 0.001), age ≥ 75 years (p = 0.02), and severe sepsis or shock (p = 0.03) at the ED. Microbiological testing in 78.4 % of cases was positive in 15.4 % (n = 15): methicillin-resistant Staphylococcus aureus (26.7 %), Pseudomonas aeruginosa (20.0 %), S. pneumoniae (13.3 %), Escherichia coli (13.3 %), others (26.7 %); the rate of MDR bacteria was 53.3 %. This study reveals high rates of mortality and MDR bacteria among NHAP hospital admissions supporting the use of empirical broad-spectrum antibiotic therapy in these patients.

Clinical and Genetic Characterization of Portuguese Patients with Pseudohypoparathyroidism Type Ib

Patients with pseudohypoparathyroidism type Ib (PHP-Ib) present hypocalcemia and hyperphosphatemia, as a consequence of a resistance to PTH action, through its G-protein-coupled receptor, in the renal tubules. This resistance results from tissue-specific silencing of the G-protein alpha-subunit (G(s)α), due to imprinting disruption of its encoding locus--GNAS. In familial PHP-Ib, maternally inherited deletions at the STX16 gene are associated to a regional GNAS methylation defect. In sporadic PHP-Ib, broad methylation changes at GNAS arise from unknown genetic causes. In this study, we describe the clinical presentation of PHP-Ib in four Portuguese patients (two of whom were siblings), and provide further insight for the management of patients with this disease. The diagnosis of PHP-Ib was made after detection of GNAS imprinting defects in each of the cases. In the siblings, a regional GNAS methylation change resulted from a known 3.0 kb STX16 deletion. In the other two patients, the broad methylation defects at GNAS, which were absent in their relatives, resulted from genetic alterations that remain to be identified. We report the first clinical and genetic study of Portuguese patients with PHP-Ib. The genetic identification of a hereditary form of this rare disease allowed an early diagnosis, and may prevent hypocalcemia-related complications.

Regulatory Cells, Cytokine Pattern and Clinical Risk Factors for Asthma in Infants and Young Children with Recurrent Wheeze

Several risk factors for asthma have been identified in infants and young children with recurrent wheeze. However, published literature has reported contradictory findings regarding the underlying immunological mechanisms. OBJECTIVES: This study was designed to assess and compare the immunological status during the first 2 years in steroid-naive young children with >or= three episodes of physician-confirmed wheeze (n=50), with and without clinical risk factors for developing subsequent asthma (i.e. parental asthma or a personal history of eczema and/or two of the following: wheezing without colds, a personal history of allergic rhinitis and peripheral blood eosinophilia >4%), with age-matched healthy controls (n=30). METHODS: Peripheral blood CD4(+)CD25(+) and CD4(+)CD25(high) T cells and their cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), GITR and Foxp3 expression were analysed by flow cytometry. Cytokine (IFN-gamma, TGF-beta and IL-10), CTLA-4 and Foxp3 mRNA expression were evaluated (real-time PCR) after peripheral blood mononuclear cell stimulation with phorbol 12-myristate 13-acetate (PMA) (24 h) and house dust mite (HDM) extracts (7th day). RESULTS: Flow cytometry results showed a significant reduction in the absolute number of CD4(+)CD25(high) and the absolute and percentage numbers of CD4(+)CD25(+)CTLA-4(+) in wheezy children compared with healthy controls. Wheezy children at a high risk of developing asthma had a significantly lower absolute number of CD4(+)CD25(+) (P=0.01) and CD4(+)CD25(high) (P=0.04), compared with those at a low risk. After PMA stimulation, CTLA-4 (P=0.03) and Foxp3 (P=0.02) expression was diminished in wheezy children compared with the healthy children. After HDM stimulation, CTLA-4 (P=0.03) and IFN-gamma (P=0.04) expression was diminished in wheezy children compared with healthy children. High-risk children had lower expression of IFN-gamma (P=0.03) compared with low-risk and healthy children and lower expression of CTLA-4 (P=0.01) compared with healthy children. CONCLUSIONS: Although our findings suggest that some immunological parameters are impaired in children with recurrent wheeze, particularly with a high risk for asthma, further studies are needed in order to assess their potential as surrogate predictor factors for asthma in early life.