Drug-induced anaphylaxis survey in Portuguese Allergy Departments.

BACKGROUND AND OBJECTIVE: Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal. METHODS: During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects. RESULTS: The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1.The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved. CONCLUSIONS: NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis.

Biological evaluation of alginate-based hydrogels, with antimicrobial features by Ce(III) incorporation, as vehicles for a bone substitute.

A novel hydrogel, based on an alginate/hyaluronate mixture and Ce(III) ions, with effective bioactive and antimicrobial ability was developed to be used as vehicle of a synthetic bone substitute producing an injectable substitute (IBS). Firstly, three different IBSs were prepared using three developed alginate-based hydrogels, the hydrogel Alg composed by alginate, the hydrogel Alg/Ch composed by an alginate/chitosan mixture and the hydrogel Alg/HA composed by an alginate/hyaluronate mixture. MG63 cells viability on the IBSs was evaluated, being observed a significantly higher cell viability on the Alg/HA_IBS at all time points, which indicates a better cell adaptation to the material, increasing their predisposition to produce extracellular matrix and thus allowing a better bone regeneration. Moreover, SEM analysis showed evident filopodia and a spreader shape of MG63 cells when seeded on Alg/HA_IBS. This way, based upon the in vitro results, the hydrogel Alg/HA was chosen to the in vivo study by subcutaneous implantation in an animal model, promoting a slight irritating tissue response and visible tissue repairing. The next step was to grant antimicrobial properties to the hydrogel that showed the best biological behavior by incorporation of Ce(III) ions into the Alg/HA, producing the hydrogel Alg/HA2. The antimicrobial activity of these hyaluronate-based hydrogels was evaluated against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans. Results showed that Ce(III) ions can significantly enhance the hydrogel antimicrobial ability without compromising the osteoconductivity improvement promoted by the vehicle association to the synthetic bone substitute.

Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva.

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.

Assessment of asthma control: clinical, functional and inflammatory aspects.

BACKGROUND: Asthma is a complex disease with numerous markers of severity/activity. Clinical assessment,functional parameters and inflammation biomarkers are the most used A correlation between them is difficult, as each one evaluates a particular aspect of the disease. OBJECTIVE AND METHODS: To explore the possible association between asthma control, pulmonary function and inflammation in patients with asthma, consecutive asthmatics underwent simultaneous spirometry (measurement of FEV1), exhaled nitric oxide (eNO) evaluation and Asthma Control Test (ACTTM) questionnaire. RESULTS: The study included 232 asthmatics (mean age: 37.48 years; 78.4%female): 43% had uncontrolled asthma (ACTTM < or = 19) with FEV1 mean values of 83.3% +/- 21.8; 48% partially controlled (ACTTM: 20-24) with FEV1 of 87.6% +/- 17; 9% complete control (ACTTM = 25) with FEV1 of 93.1 +/- 20.6. The relation ACTTM/FEV1 and ACTTM/FEF 25-75% was statistically significant (p = 0.001 and p = 0.034, respectively). Among patients with eNO < 35 ppb, 66% had FEV1 > 80% and 52% had ACTTM > 19. No association was found combining ACTTM/eNO or FEV1/eNO. A subgroup of 66 patients was evaluated twice. CONCLUSION: An association was found between ACTTM and spirometry, with higher ACTTM scores reflecting less bronchial obstruction. The authors advise a combined approach in asthma follow-up, involving clinical aspects, functional parameters and inflammation biomarkers, although in some circumstances ACT could be a valid instrument to be used alone to assess control.

Infective endocarditis in intravenous drug abusers: an update.

Infective endocarditis despite advances in diagnosis remains a common cause of hospitalization, with high morbidity and mortality rates. Through literature review it is possible to conclude that polymicrobial endocarditis occurs mainly in intravenous drug abusers with predominance in the right side of the heart, often with tricuspid valve involvement. This fact can be associated with the type of drug used by the patients; therefore, knowledge of the patient's history is critical for adjustment of the therapy. It is also important to emphasize that the most common combinations of organisms in polymicrobial infective endocarditis are: Staphylococcus aureus, Streptococcus pneumonia and Pseudomonas aeruginosa, as well as mixed cultures of Candida spp. and bacteria. A better understanding of the epidemiology and associated risk factors are required in order to develop an efficient therapy, although PE studies are difficult to perform due to the rarity of cases and lack of prospective cohorts.

Determining the negative predictive value of provocation tests with beta-lactams.

BACKGROUND: The beta-lactam allergic work-up is mostly standardized. However, the negative predictive value of drug provocation tests is not yet well established. METHOD: A historical-prospective multicentre cohort study was conducted in four centres (one in France, one in Portugal, two in Italy) to assess the negative predictive value of provocation tests with beta-lactams in patients initially tested for a suspicion of drug allergy/hypersensitivity. Patients were contacted at least 6 months after the work-up, between 2003 and 2007. A new allergic work-up was proposed to reacting patients. RESULTS: Among the 457 patients included, 365 (79.9%) were followed up (159 [79.1%] from France, 153 [82.7%] from Italy and 53 [74.6%] from Portugal). Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). CONCLUSION: Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups.

Acute lupus hemophagocytic syndrome: report of a case.

Hemophagocytic Syndrome is a clinical condition characterized by the activation of either macrophages or histiocytes with a prominent hemophagocytosis feature in the bone marrow and other reticuloendothelial systems. It leads to the phagocytosis of erythrocytes, leukocytes, platelets and their precursors. The presence of hemophagocytosis can be associated to infections, malignancies, autoimmune diseases, drugs and a variety of other medical conditions. We report a case of a previously healthy 36 year-old woman that developed hemophagocytosis at the same time that fulfilled diagnostic criteria for systemic lupus erythematosus. Lupus related hemophagocytic syndrome is a rare and potentially fatal entity. It offers significant differential diagnosis challenges and requires urgent therapeutic intervention. There are only few cases reported in the literature. However, much is still needed in order to better understand its causes, all the immunopathogenic mechanisms, as well as its clinical and therapeutic aspects.

Immediate hypersensitivity to penicillins with negative skin tests--the value of specific IgE.

The determination of specific IgE in patients with history of penicillins hypersensitivity is simple, safe and widely available. The positive and negative predictive values of this determination, however, are not yet established. In order to evaluate them, we performed specific IgE determination and diagnostic drug challenges in a group of 22 patients with a clear history of immediate penicillins hypersensitivity but negative skin tests. In this sample, the positive and negative predictive values were 29% and 87%, respectively. This seems to indicate that a positive specific IgE is not enough to confirm the diagnosis, and further study is necessary.

The role of non-invasive dynamic tests in the diagnosis of Cushing's syndrome.

OBJECTIVE: To evaluate the role of non-invasive dynamic tests in the diagnosis and differential diagnosis of Cushing's syndrome (CS). METHODS: We studied laboratory features of 74 patients with endogenous CS, subdivided as follows: 46 (62.1%) with Cushing's disease (CD), 21 (28.3%) with an adrenal tumor, and 7 (9.5%) with ectopic ACTH syndrome (EAS). RESULTS: In 100% of cases of CS we found serum cortisol levels greater than 1.8 microg/dl after low-dose dexamethasone suppression tests (LDDST), as well as elevation of midnight serum or salivary cortisol. However, urinary free cortisol was normal in 11.5% of patients. ACTH levels were suppressed in patients with adrenal tumors, normal or high in CD and invariably increased in EAS. After the 8-mg overnight dexamethasone suppression test (HDDST), serum cortisol suppression >50% was observed in 79.5% of cases of CD and in 28.6% of subjects with EAS, whereas cortisol suppression >80% was only found in CD. After stimulation with CRH or desmopressin an ACTH rise > or =35% occurred in 86.5% of individuals with CD and 14.3% of those with EAS, whereas an ACTH rise > or =50 achieved 100% specificity. Moreover, the combination of serum cortisol suppression >50% after HDDST and an ACTH increase > or =35% after the administration of CRH or desmopressin only occurred in CD. CONCLUSION: Our findings demonstrate that LDDST had 100% sensitivity for the diagnosis of CS and that HDDST and stimulation tests with CRH or desmopressin may be very useful for confirmation of CS etiology when analyzed together or when more stringent cut-offs are used.

A clinical report of bone regeneration in maxillofacial surgery using bonelike synthetic bone graft.

The objective of this study is to evaluate the osteoconductivity and bioactivity of the Bonelike graft in repairing surgical cystic bone defects. Bonelike is implanted in 11 patients, aged between 24 and 53 years with a mean age of 36 years, consisting of 5 men and 6 women. According to the standard follow up protocols, radiological examinations are performed and Bonelike/bone retrieved samples have been analyzed histologically using non-decalcified sections obtained perpendicular to bone length axis. Radiographic examination and histological results clearly demonstrate an extensive new bone formation apposed on Bonelike granules with a significant degree of maturation. These clinical applications in maxillary bone defects indicate perfect bone bonding between new bone formed and Bonelike granules, along with partial surface biodegradation. This quick and effective osteoconductive response from Bonelike may reduce the time needed to reconstruct the bone defected area of patients.

Human osteoblast response to silicon-substituted hydroxyapatite.

Human osteoblasts were cultured on hydroxyapatite (HA), 0.8 wt % silicon substituted hydroxyapatite (Si-HA) and 1.5 wt % Si-HA discs. The influence of these substrates on cell behaviour in vitro was assessed by measuring total protein in the cell lysate and the production of several phenotypic markers: collagen type I (COL I), alkaline phosphatase (ALP), osteocalcin (OC), and the formation of bone mineral. After 7 days, beta-glycerophosphate and physiological levels of hydrocortisone were added to the culture medium to stimulate cell differentiation and mineral production. There was a significantly higher production of ALP on 1.5 wt % Si-HA at day 7 following which, the addition of hydrocortisone promoted the differentiation of cells on the other two substrates. Hydrocortisone addition also decreased the production of OC. During the period, when hydrocortisone was present, no significant difference in behavior was seen between cells on Si-HA and HA; however, following removal of hydrocortisone, cells responded to 0.8 wt % Si-HA with a significant increase in protein production. Using fluorescence microscopy, nodular structures labeled with tetracycline were observed on the surface of all substrates after 21 days. These structures were deposited on areas of high cell density but were not related to the presence or level of silicon in the substrate. These results indicate that human osteoblasts are affected by the presence of silicon in the HA substrate and that the timing of these effects may be dependent upon the level of silicon substitution.

Differentiation of mononuclear precursors into osteoclasts on the surface of Si-substituted hydroxyapatite.

In healthy bone, resorption and synthesis are in perfect coordination. In previous studies we demonstrated that the incorporation of silicon into the hydroxyapatite (HA) lattice enhances the proliferation and differentiation of human osteoblasts. Therefore, the aim of this study was to demonstrate the effect of silicon-substituted HA (0.8 and 1.5 wt % Si-HA) on the differentiation of mononuclear cells into osteoclasts, using two different starting cultures, peripheral blood mononuclear cells (PBMC) and monocytes expressing the CD14 antigen (CD14+). Through this study, it was possible to demonstrate that Si-HA allows the differentiation of mononuclear cells into mature osteoclasts, independent of the starting culture, PBMC or CD14+. Most of the cells on the surface of the materials expressed osteoclastic markers: actin rings, several nuclei, positivity for tartrate-resistant acid phosphatase (TRAP), and vitronectin receptor. In the presence of osteoclasts, a higher release of calcium and phosphate into the medium from the 1.5 wt % Si-HA substrate was detected when compared to the HA substrate; therefore, these results indicate higher osteoclastic resorptive activity on the 1.5 wt % Si-HA surface. Si-HA can be resorbed by cellular mechanisms and have a stimulatory effect on osteoclasts, although the underlying mechanism is still poorly understood.

[Intradiploic encephalocele in an adult. A case report and review of the literature]. / Encéphalocèle intra-diploïque de l'adulte. A propos d'un cas et revue de la littérature.

We describe a rare case of parietal intradiploic encephalocele in a 51-year-old woman with no history of head trauma. The patient presented with a 1-month history of left hemiparesthesia. A hard indolent scalp lesion was palpable on examination in the right parietal area. Skull x-rays and cranial computed tomography examination demonstrated a lytic lesion that was consistent with a malignant osteolytic skull lesion. Magnetic resonance imaging of the head revealed an intradiploic cyst that included a round tissue mass contiguous with the parietal cortex. Surgery confirmed the diagnosis of encephalocele and the patient underwent surgical resection of the herniated brain, duraplasty, and cranioplasty. The presenting hemiparesthesia persisted at the 6-month follow-up. Encephaloceles of the cranial vault are a rare complication of skull fractures and rarely occur in adults. These lesions can be difficult to distinguish from congenital encephaloceles in patients with no history of head trauma. The pathogenesis, clinical and radiological nuances and the role of surgery are discussed.

Primary care physicians' ability to diagnose the most prevalent respiratory diseases.

BACKGROUND: There are few reports on the ability of primary care physicians (PCPs) to diagnose acute and chronic respiratory diseases. We assessed the agreement between PCPs and pulmonologists in diagnosing pulmonary tuberculosis (TB), chronic obstructive pulmonary disease (COPD), asthma and acute respiratory infections (ARI). SETTING: Metropolitan Region of Belo Horizonte, State of Minas Gerais, Brazil. METHODS: PCPs filled out a symptom-based questionnaire for adult patients presenting with respiratory symptoms. Their diagnoses were compared to those of three pulmonologists who reviewed the data independently without seeing the patients. Agreement between PCP decisions and those of the pulmonologists was assessed. RESULTS: Among a total of 554 patients, 60 PCPs correctly diagnosed 42.4% as having ARI, 17.3% asthma, 15.7% COPD and 12.4% suspected TB. Agreement between the PCPs and the pulmonologists was as follows: 0.53 for asthma (95%CI 0.45-0.60), 0.53 (95%CI 0.46-0.60) for ARI, 0.45 (95%CI 0.34-0.57) for TB and 0.40 (95%CI 0.29-0.50) for COPD. CONCLUSION: Only reasonable to moderate agreement was found between PCPs and pulmonologists in diagnosing the most prevalent respiratory conditions. This result emphasises the need to adopt measures and provide tools to improve the diagnostic skills of PCPs for patients presenting with respiratory symptoms.

[Imaging in acute toxic encephalopathy]. / Imagerie des encephalopathies toxiques aigues.

Neuroimaging, particularly MR imaging, plays a major role for the diagnosis of many acute toxic encephalopathies. Toxic disorders are related to drugs (immunosuppressive agents, chemotherapeutic agents, anti-epileptic drugs, heroin...), to metals (lead, manganese, mercury...), and to industrial and environmental chemicals (solvent, carbon monoxide...). MR imaging with diffusion and perfusion imaging provides information regarding brain lesions induced by the toxic agents (vasogenic edema, cytotoxic edema, infarction, hemorrhage, demyelination...).

Retrospective study of a pioneer antenatal screening program with 8,477 pregnant women in Brazil.

PURPOSE OF INVESTIGATION: To analyze the results of a statewide screening program inaugurated in 2002 in Mato Grosso do Sul, METHODS: Retrospective audit of the screening results of 8,477 pregnant women for 11 diseases in 19 tests. Local health centers of the Brazilian Unified System of Health/State Program of Pregnant Protection (SUS/PEPG) and central reference processing laboratories, both in and out of state were involved. Pregnant women were referred to the program by medical staff principally at local health centers, between November 2002 and February 2003. Primary screening with filter-paper blood samples was carried out with positives being resampled and sera appropriately tested. RESULTS: The detailed test results are given below; the most frequent diseases serodiagnosed were hepatitis B, syphilis, HIV and Chagas' disease. One case of maternal phenylketonouria (PKU) was encountered. CONCLUSION: The diagnosis of 11 diseases of importance for mothers and their offspring provides an epidemiological profile of Brazil, but must be matched by opportunities to elaborate new control strategies and improve health care during pregnancy.

[Osteochondromas of the spine. A diagnosis to consider in spinal cord compression syndromes]. / Osteocondromas da coluna vertebral. Um diagnóstico a considerar nas sindromes de compressão medular.

The authors reviewed 312 cases of solitary and multiple osteochondromas seen in SARAH Hospital for the Locomotor System during a period of 13 years-from 1982 to 1994. They selected six cases of patients with osteochondromas of the spine, corresponding to 1.92% of the total number of diagnosed cases of this entity. The selected cases were submitted to roentgenographic examination that comprised plain roentgenograms, myelography, computerized tomography and, in one of them, magnetic resonance imaging. They were submitted to decompressive surgical procedures (including laminectomy) with exeresis of the lesions and posterior histopathological examination which confirmed the initial diagnostic hypothesis. This study also includes a review of the possible mechanisms implicated in the pathogenesis of the disease.

[Spinal cord schwannoma: case report]. / Schwannoma intramedular. Relato de caso.

The intramedullary localization of schwannomas is rare, corresponding to 0.3% of all intraspinal tumors. The authors report the case of a 52-year-old white female patient that presented with symptoms of spinal compression by the presence of an intramedullary schwannoma at the level C4-C6. There were no symptoms of neurofibromatosis, entity frequently related to the lesion. The magnetic resonance imaging examination and the per-operatory biopsy were decisive factors in planning and executing the treatment, by establishing the characteristics, location and diagnosis of the lesion. Its delimitation and posterior location have facilitated total surgical exeresis. The transoperatively histopathologic examination allowed adequate surgical procedure. The Schwann cell is not found normally in the central nervous system and its presence in this site has been subject of many theories exposed in this paper, which proposes comprehensive review of the clinical aspects, imaging diagnosis, pathology, differential diagnosis and treatment of schwannomas. It is probable that, with the advances verified in the available diagnostic methods, a greater number of these lesions may be diagnosed in the future.