Homozygous V377I mutation causing mevalonate kinase.

Hyperimmunoglobulinaemia D syndrome (HIDS) is a rare autosomal recessive disorder caused by mutations in the mevalonate kinase (MVK) gene, located on chromosome 12. The most common mutation identified in MVK gene so far is V377I. Compound heterozygotes that include this variant may exhibit a more severe phenotype of the disease and homozygotes are rarely found in clinical practice probably they express a milder phenotype. HIDS is a chronic autoinflammatory disease characterised by recurrent febrile episodes, associated with lymphadenopathies, abdominal pain, rash and arthritis. These flares can be triggered by vaccination, minor trauma, surgery and stress.We report a case of a 2-year-old girl who had recurrent attacks of fever associated with cervical lymphadenopathy, macular erythematous skin rash, abdominal pain and aphthous ulcers in the mouth. The patient was found to excrete elevated amounts of urinary mevalonic acid and a homozygous V337I mutation in the MVK gene was identified.

Granulomatous Hepatitis Following Intra-Vesical Instillation of Bacillus Calmette-Guérin for Treatment of Bladder Cancer.

Intra-vesical instillation of bacillus Calmette-Guérin (BCG) is an important treatment modality of superficial bladder cancer. It is usually well tolerated, although some adverse reactions can occur. One possible yet rare complication is granulomatous hepatitis, that is thought to be caused either by BCG infection or a hypersensitivity reaction to the bacillus. We present a case of a 79-year-old apparently immunocompetent patient who developed granulomatous hepatitis a few months after BCG administration for bladder cancer immunotherapy. It is important to notice that acid-fast smears and cultures are often negative, and these should not exclude diagnosis nor delay treatment. Our case highlights the importance of clinical suspicion and prompt initiation of appropriate treatment.

Complicated EBV infection in a healthy child.

The Epstein-Barr virus (EBV) is highly prevalent throughout the population. Although in most cases, the infection has a good prognosis, it can cause severe complications. We report a case of a healthy child with a primary EBV infection that evolved with two rare complications. She first presented in the emergency room with fever and sore throat, and was diagnosed with tonsillitis and medicated with antibiotic. She returned 7 days later for fatigue, vomiting and abdominal pain. The examination revealed tonsillitis, swollen cervical lymph nodes and pain in the right hypochondrium. An abdominal ultrasound was performed, compatible with acute acalculous cholecystitis. She was admitted in the paediatric nursery and medicated with intravenous antibiotics. The EBV serology revealed primary infection. Two days later, she developed cardiogenic shock and had to be transferred to an intensive care unit under mechanical ventilation and inotropics. She was discharged 12 days later, keeping a moderate left ventricular dysfunction.

The Influence of Gender in The Prognostic Impact of Diabetes mellitus in acute Pulmonary Embolism.

Diabetes mellitus (DM) predicts ominous outcomes in acute pulmonary embolism (PE). The influence of gender on the prognostic impact of DM in PE is unknown. We did a retrospective analysis of a cohort of patients hospitalized with PE between 2006 and 2013. The exclusion criteria were age <18, non-pulmonary veins thromboembolism, recurrent PE, chronic thromboembolic pulmonary hypertension, no radiologic confirmation of PE, and active neoplasia. The primary endpoint was all-cause mortality. The follow-up was from diagnosis until October 2017. We assessed the prognostic impact of DM using a multivariate Cox regression analysis. The analysis was stratified according to gender. The interaction between gender and DM in the outcome of patients with PE was tested. We studied 577 PE patients (median age 65 years, 36.9% men, 19.8% diabetic). The genders were similar regarding the prevalence of DM, the extension and location of PE, and the thrombolytic therapy or brain natriuretic peptide (BNP) value. Diabetics presented higher all-cause mortality (Hazard ratio (HR) = 2.33 (95% confidence Interval (CI) 1.513.61)) when compared with non-diabetics. However, when analysis was stratified according to gender, DM was independently associated with a worse prognosis only in women (HR = 2.31 (95% CI 1.453.65)), while in men the HR was 1.10 (95% CI 0.592.04). The interaction between gender and DM was significant (p = 0.04). Gender influences the prognostic impact of DM in acute PE. Diabetic women with PE have twice the long-term mortality risk, while DM is not mortality-associated in men.

Transient mutism, pathological laughter and cerebellar ataxia after primary varicella-zoster virus infection.

Acute postinfectious cerebellitis is characterised by inflammatory involvement of the cerebellum and consequent cerebellar dysfunction, usually presenting a benign and self-limited course. Common symptoms described in the literature include ataxia, peripheral facial paralysis, aphasia, spinal dysfunction and eventually hydrocephalus. We describe a rare presentation of acute cerebellitis after varicella, in a 6-year-old child, who presented with ataxia, dysmetria, mutism and pathological laughter.

Canine leishmaniosis. Modulation of macrophage/lymphocyte interactions by L. infantum.

Canine leishmaniosis, caused by Leishmania infantum, is a systemic disease with variable clinical signs and a progressive evolution. This disease is characterized by impaired T cell-mediated immune response, which has been associated with disease chronicity and high mortality. Protective immunity against leishmaniosis is thought to be mediated by T cell and cytokine production. The T cell activation requires a primary signal delivered by the major histocompatibility complex (MHC) molecules present on the surface of antigen presenting cells, and a non-specific signal generated by co-stimulatory molecules. To characterize canine immune responses in the presence of L. infantum parasites or their antigens, in vitro cell cultures of canine macrophages and lymphocytes were established, and the macrophages presenting MHC class II molecules were evaluated as well as the expression of IL-12 and CD80-86 co-stimulatory molecules and nitric oxide production. The results showed for the first time the up-regulation of MHC class II molecules on the surface in canine peripheral blood monocyte-derived macrophages during L. infantum infection in the presence of lymphocytes. In addition, a lack of co-stimulatory expression and a reduced release of nitric oxide were observed, suggesting a loss of T cell function and consequently an inactivation of the macrophage oxidative burst which, in turn, favors the survival of Leishmania. These results constitute a new contribution for the understanding of the interactions between L. infantum and the canine immune system.

Development of advanced image analysis techniques for the in situ characterization of multiphase dispersions occurring in bioreactors.

Fermentation bioprocesses typically involve two liquid phases (i.e. water and organic compounds) and one gas phase (air), together with suspended solids (i.e. biomass), which are the components to be dispersed. Characterization of multiphase dispersions is required as it determines mass transfer efficiency and bioreactor homogeneity. It is also needed for the appropriate design of contacting equipment, helping in establishing optimum operational conditions. This work describes the development of image analysis based techniques with advantages (in terms of data acquisition and processing), for the characterization of oil drops and bubble diameters in complex simulated fermentation broths. The system consists of fully digital acquisition of in situ images obtained from the inside of a mixing tank using a CCD camera synchronized with a stroboscopic light source, which are processed with a versatile commercial software. To improve the automation of particle recognition and counting, the Hough transform (HT) was used, so bubbles and oil drops were automatically detected and the processing time was reduced by 55% without losing accuracy with respect to a fully manual analysis. The system has been used for the detailed characterization of a number of operational conditions, including oil content, biomass morphology, presence of surfactants (such as proteins) and viscosity of the aqueous phase.

Effect of topical application of fibronectin in duodenal wound healing in rats

Fibronectin (FN), a large family of plasma and extracellular matrix glycoproteins, plays an important role in wound healing. PURPOSE: To evaluate the effect of fibronectin on the healing of sutured duodenal wounds, correlating with the serum and tissue level of the substance. METHODS: An experimental study was done in 30 adult Wistar rats divided into two group. In the control group (n=15) a duodenal suture was treated with saline solution 0,9 percent and in the test group the duodenal wounds were treated with 1 percent FN. The duodenal wound healing process was studied in the 5th, 7tn and 10th postoperative days, by histological sections stained by hematoxylin-eosin, Masson trichromic and immunohistochemical reaction for FN. A digital histological grading system was used to obtain a score for each group and to observe the healing process. RESULTS: the FN was present in the several layers of the duodenum and the cellular and plasmatic FN increased with the evolution of healing. In the test group the FN enhanced the wound healing within 5, 7 and 10 days after injury, when compared with the control group. CONCLUSION: The topical use of FN in duodenal sutured wounds in rats enhances healing by stimulating the appearence of fibroblasts into the wound site and development of granulation tissue. This acceleration of the repair process may have an important application in the healing of duodenal wounds.