Treatment of chromoblastomycosis with itraconazole, cryosurgery, and a combination of both

Background Chromoblastomycosis is a subcutaneous mycosis, seen frequently in tropical areas, and caused by dematiaceous fungi. It produces nodulo-verrucous lesions in the arms and legs. There is no treatment of choice for this disease and sometimes a combination of chemotherapy and physical therapy is necessary. Methods The study included 12 patients diagnosed with chromoblastomycosis by means of fungal and histopathologic tests. The patients were assigned to three treatment groups: patients with small lesions, not greater than 15 cm² in area, were assigned to Group 1, in which the treatment consisted of itraconazole 300 mg/day, or to Group 2, in which the treatment consisted of one or more sessions of open-spray cryosurgery. Patients with large lesions were assigned to Group 3 and started treatment with itraconazole 300 mg/day, until a maximal reduction of lesions occurred, and then underwent one or several cryosurgery sessions. Clinical, fungal, and laboratory tests were performed in each group before, during, and at the completion of treatment. Results Positive cultures of Fonsecaea pedrosoi were obtained in 11 out of 12 patients. Two out of four patients in Groups 1 and 3 had a clinical and fungal cure and the remaining patients experienced significant improvement. All four patients included in Group 2 achieved a cure. No important side-effects were seen among the patients included in any of the two itraconazole groups, and only two out of eight patients reported gastric discomfort. The cryosurgery group reported only normal complications of the process, such as edema and pain; two out of eight patients had a superimposed infection. Conclusions The results of itraconazole and cryosurgery were good in cases with small lesions; antifungal therapy being more appropriate for flexion areas. The combination of itraconazole, to reduce the size of the lesions, with subsequent treatment of the remaining lesions with cryosurgery, represents a new alternative in the treatment of patients with large lesions. Both types of therapy are considered safe, with few side-effects.     

Opportunistic filamentous mycoses: aspergillosis, mucormycosis, phaeohyphomycosis and hyalohyphomycosis

Opportunistic filamentous mycoses are widely distributed all over the world. They are rarely observed in Europe but are common in developing countries. The most common are the aspergilloses (due to Aspergillus spp.) mostly in neutropenia and immunosuppression; the mucormycoses characterized by rapid progression in patients with diabetic ketoacidosis; the phaeohyphomycoses due to pigmented fungi causing either a mild superficial or a very serious deep disease and the hyalohyphomycoses due to hyaline filamentous fungi (Fusarium spp., Pseudallescheria spp., Scopulariopsis spp.). Cutaneous manifestations are usually secondary to dissemination from pulmonary or visceral disease; primary cases are less frequent and due to direct inoculation into the skin. We review epidemiological, clinical, diagnostic, and therapeutic data on the four most important opportunistic filamentous mycoses: aspergillosis, mucormycosis, phaeohyphomycosis and hyalohyphomycosis.     

Simultaneous low (1 Hz)- and high (10 Hz)-frequency bilateral transcranial magnetic stimulation in a patient with severe depression and crohn disease

ABSTRACT: We present a case report in which electroconvulsive therapy had a good effect for the treatment of depression in association with Crohn disease, but adverse effects limited its use. Repetitive transcranial magnetic stimulation was tried both in a conventional way (high frequency over the left dorsolateral prefrontal cortex) and in a bilateral sequential way (high frequency in the same region followed in the same session by low frequency on the right side). Finally, bilateral simultaneous stimulation (high frequency over the left and low frequency over the right side) was tried and resulted in a response similar to that of electroconvulsive therapy.     

Utility of helical computed tomography to evaluate the invasion of actinomycetoma; a report of 21 cases

BACKGROUND: Actinomycetoma is a chronic infection caused by several aerobic actinomycetes; it is a relatively frequent condition in tropical countries like Mexico. It is important to be aware of the extension and depth of the disease (bone and visceral) to make the prognosis and select treatment. OBJECTIVES: Our objective was to evaluate actinomycetomas using helical computed tomography (HCT) as well as its three-dimensional (3D) reconstruction. MATERIAL AND METHODS: Prospective study of clinically and microbiologically proven cases of actinomycetomas, all of them recently diagnosed and untreated or unresponsive to various treatments. All patients underwent simple and contrast HCT with various helical slices of the involved zones. Then three-dimensional reconstructions on the sagittal and coronal planes were made. RESULTS: Twenty-one patients with actinomycetomas were included, 19 males and two females, with a mean age of 35.5 years and mean duration of disease of 4.1 years. The disease was located in the lower limbs in 81%, and in the upper limbs and trunk in 19%. Twenty of the 21 cases were caused by Nocardia brasiliensis and one by Actinomadura madurae. In all patients the disease was localized to the skin and subcutaneous tissue; 76.2% had muscular involvement; 23.8% visceral involvement; 9.5% had bone involvement and 9.5% vascular involvement. The affected area was determined in each case. CONCLUSIONS: HCT provides precise information about the grade of invasion at diverse levels such as visceral, muscular and vascular systems, and the calculation of the affected area.     

Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein

The maturation of dendritic cells (DCs) allows these antigen-presenting cells to initiate immunity. We pursued this concept in situ by studying the adjuvant action of alpha-galactosylceramide (alphaGalCer) in mice. A single i.v. injection of glycolipid induced the full maturation of splenic DCs, beginning within 4 h. Maturation was manifest by marked increases in costimulator and major histocompatibility complex class II expression, interferon (IFN)-gamma production, and stimulation of the mixed leukocyte reaction. These changes were not induced directly by alphaGalCer but required natural killer T (NKT) cells acting independently of the MyD88 adaptor protein. To establish that DC maturation was responsible for the adjuvant role of alphaGalCer, mice were given alphaGalCer together with soluble or cell-associated ovalbumin antigen. Th1 type CD4+ and CD8+ T cell responses developed, and the mice became resistant to challenge with ovalbumin-expressing tumor. DCs from mice given ovalbumin plus adjuvant, but not the non-DCs, stimulated ovalbumin-specific proliferative responses and importantly, induced antigen-specific, IFN-gamma producing, CD4+ and CD8+ T cells upon transfer into naive animals. In the latter instance, immune priming did not require further exposure to ovalbumin, alphaGalCer, NKT, or NK cells. Therefore a single dose of alphaGalCer i.v. rapidly stimulates the full maturation of DCs in situ, and this accounts for the induction of combined Th1 CD4+ and CD8+ T cell immunity to a coadministered protein.     

Durability and clinical experience using a bovine pericardial prosthetic aortic valve

ObjectivesTo report the implant experience and long-term outcomes from a large tertiary care referral center on surgical aortic valve replacement (SAVR) with a contemporary stented pericardial bioprosthesis with anticalcification treatment.MethodsPatients underwent SAVR using the Trifecta valve at a single institution. Endpoints included procedural outcomes, adverse events, prosthesis–patient mismatch (PPM), long-term survival, and valve durability. Follow-up included 30-day, 6-month, and annual assessments. Treatment for structural valve deterioration (SVD) included surgical explant and valve-in-valve (V-in-V) transcatheter aortic valve implantation (TAVI).ResultsSAVR was performed in 1241 patients (median age, 73.5 ± 6.4 years; 54% male; median logistic EuroSCORE, 7.8) with concomitant procedures in 713 cases (57.5%). Intraprocedural mortality was 1.4%, and 30-day mortality was 6.0%. At hospital discharge, 68 patients (5.5%) had moderate PPM, and no patients had severe PPM. Adverse events included cardiac arrhythmias (44.7%, mostly atrial fibrillation), respiratory failure (22.9%), acute renal failure requiring temporary renal replacement therapy (12.9%), and low cardiac output syndrome (3.3%). Follow-up data were available over a total of 5469 patient-years (median duration of follow-up, 4.7 years). Freedom at 8 years from all-cause mortality, valve-related mortality, reoperation for SVD (redo SAVR or V-in-V TAVI), and endocarditis were 78.4%, 98.0%, 93.3%, and 96.5%, respectively. Of the 30 patients with SVD, 17 were treated by V-in-V TAVI and 13 underwent surgical explant.ConclusionsOutcomes from this large single-center cohort at increased surgical risk demonstrate excellent long-term durability of the Trifecta valve for SAVR and feasibility of treating SVD by V-in-V TAVI.     

Relation between calcium levels and adenosine deaminase activity in serum in pre- and postpartum of dairy cow

The transition period is marked by intense metabolic changes that defy calcium homeostasis, and compromise the immune capacity of dairy cows, what denotes interaction between metabolic status and immune activity. The adenosine deaminase (ADA) regulates adenosine levels; a molecule with anti-inflammatory properties that can act in reducing the production of pro-inflammatory cytokines and reactive oxygen species (ROS), which in exacerbated production is harmful to health. Therefore, the aim of this study was to evaluate the relationship between seric levels of calcium levels and ADA in prepartum and postpartum of dairy cows. To evaluate these variables, Holstein cows were subjected to blood collection in the transition period (days 20, 10, and 5 prepartum; and days 3, 7, 12, and 20 postpartum) and where we evaluated the serum levels of calcium and the ADA activity. An increase in the ADA activity was observed mean day 20 to day 10 postpartum (P < 0.001). Numerically, in other periods evaluated, ADA activity was higher when compared to day 20 prepartum. The serum calcium significantly reduced from 5 days prepartum, keeping smaller the day 20 prepartum until day 12 postpartum (P < 0.02). There was a negative correlation between serum calcium levels and ADA activity. The increase of ADA can be related to modulation of the inflammatory response that occurs during the transition period for cows.     

Analgesia de parto no neuroeixo: uma revisão da literatura

The use of analgesia techniques for labor has become increasingly frequent, with neuraxial techniques being the most commonly used and most effective. Labor pain entails a number of physiological consequences that may be negative for the mother and fetus, and therefore must be treated. This literature review was performed through a search in the PubMed database, from July to November 2016, and included articles in English or Portuguese, published between 2011 and 2016 or anteriorly, if relevant to the topic. The techniques were divided into the following topics: induction (epidural, combined epidural‐spinal, continuous spinal, and epidural with dural puncture) and maintenance of analgesia (continuous epidural infusion, patient‐controlled epidural analgesia, and intermittent epidural bolus). Epidural analgesia does not alter the incidence of cesarean sections or fetal prognosis, and maternal request is a sufficient indication for its initiation. The combined technique has the advantage of a faster onset of analgesia; however, patients are subject to a higher incidence of pruritus resulting from the intrathecal administration of opioids. Patient‐controlled analgesia seems to be an excellent technique, reducing the consumption of local anesthetics, the number of anesthesiologist interventions, and increasing maternal satisfaction.     

Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4-48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of alphaDEC-205:OVA to DCs in the steady state initially induced 4-7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with alphaDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic alphaCD40 antibody produced large amounts of interleukin 2 and interferon gamma, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.