In Vitro Effect of Sulfamethoxazole-Trimethoprim against Histoplasma capsulatum var. capsulatum

This study evaluated the in vitro effect of sulfamethoxazole-trimethoprim against Histoplasma capsulatum var. capsulatum isolated from HIV-positive patients. The drugs were tested by microdilution testing in accordance with the CLSI guidelines. All of the strains were inhibited by sulfamethoxazole-trimethoprim, with MIC ranges of 0.039 (sulfamethoxazole)/0.0078 (trimethoprim) mg/ml to 0.625/0.125 mg/ml for mycelial forms and 0.0025/0.0005 to 0.02/0.004 mg/ml for yeast-like forms. However, in vivo studies are necessary to evaluate the significance of these results.Histoplasmosis is an infection caused by the dimorphic fungus Histoplasma capsulatum. It is endemic in the Americas (3) and is currently one of the most important systemic infections in Brazil (6). In a retrospective study carried out in Ceará state (northeastern Brazil) from 1995 to 2004, 164 histoplasmosis cases were found in HIV-positive patients (4).The treatment of histoplasmosis depends on the infection''s severity and clinical manifestation, along with individual risk factors (9, 13). Because of the increase in histoplasmosis, particularly in HIV-positive patients, as well as the development of antifungal resistance associated with refractory and repeated infections (13), there is a need for seeking new therapeutic options for this mycosis. Therefore, this study aimed at testing the in vitro activity of sulfamethoxazole-trimethoprim (SMX-TMP) against H. capsulatum var. capsulatum strains isolated from AIDS patients.A total of 84 clinical strains of H. capsulatum isolated from two different biogeographic regions in Brazil were included in this study. Of them, 68 came from Ceará (northeastern semiarid region) and 16 from southeastern states (a subtropical region). The strains were obtained from the collection of the Specialized Medical Mycology Center of Ceará Federal University and were handled in our level 3 biosecurity laboratory.For each strain, a combined solution of SMX-TMP (Roche, Brazil) was used at a concentration range of 0.0025 mg/ml SMX/0.0005 mg/ml TMP and 20/4 mg/ml. The inocula were prepared as described by Li et al. (10), with some modifications. Briefly, H. capsulatum strains were cultured in the mycelial phase onto brain heart infusion (BHI) agar for 7 days at 28°C, and then 2 ml of sterile saline was added to each culture. The surfaces of the mycelia were harvested with a swab. To obtain yeast cells, isolates were cultured on agar BHI with sheep blood (10%) at 35°C and were maintained through weekly passages (7). The supernatant was read in a spectrophotometer at 530 nm, and the transmittance was adjusted to 90 to 95%. The suspensions then were diluted to obtain an inoculum of 0.5 × 10³ to 2.5 × 10⁴ CFU/ml, as demonstrated by quantitative colony counts on Sabouraud dextrose agar (10). Susceptibility tests were carried out as described by Nakai et al. (11), except that the readings were performed after 7 or 4 days for mycelial and yeast growth, respectively. For SMX-TMP, the MIC was defined as the lowest concentration at which no visible growth was observed (14). The differences in the MICs between northeastern and southeastern strains were evaluated by Student''s t test (P < 0.05). Susceptibility control tests were performed with amphotericin B (AMB) against 84 and 7 H. capsulatum strains in mycelial and yeast-like forms, respectively. SMX-TMP quality control was carried out with Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853.All H. capsulatum strains were inhibited by SMX-TMP, with MICs ranging from 0.039/0.0078 to 0.625/0.125 mg/ml for the mycelial forms and 0.0025/0.0005 to 0.02/0.004 mg/ml for the yeast-like forms. The SMX-TMP MICs for strains from northeastern Brazil presented geometric means of 0.1544 mg/ml for sulfamethoxazole and 0.0309 mg/ml for trimethoprim for the mycelial forms and 0.0141 mg/ml for sulfamethoxazole and 0.0028 mg/ml for trimethoprim for yeast-like forms. The geometric means for the strains from southeast Brazil were 0.1152 mg/ml for sulfamethoxazole and 0.0230 mg/ml for trimethoprim for the mycelial forms and 0.0079 mg/ml for sulfamethoxazole and 0.0016 mg/ml for trimethoprim for yeast-like forms (Table ​(Table11).

TABLE 1.

MICs of SMX/TMP against strains of H. capsulatum var. capsulatum in yeast-like and mycelial forms from northeastern and southeastern Brazil^a

Correlations between forced oscillation technique parameters and pulmonary densitovolumetry values in patients with acromegaly

The aims of this study were to evaluate the forced oscillation technique (FOT) andpulmonary densitovolumetry in acromegalic patients and to examine the correlationsbetween these findings. In this cross-sectional study, 29 non-smoking acromegalicpatients and 17 paired controls were subjected to the FOT and quantification of lungvolume using multidetector computed tomography (Q-MDCT). Compared with the controls,the acromegalic patients had a higher value for resonance frequency [15.3 (10.9-19.7)vs 11.4 (9.05-17.6) Hz, P=0.023] and a lower value for meanreactance [0.32 (0.21-0.64) vs 0.49 (0.34-0.96) cmH₂O/L/s², P=0.005]. In inspiratory Q-MDCT, the acromegalicpatients had higher percentages of total lung volume (TLV) for nonaerated and poorlyaerated areas [0.42% (0.30-0.51%) vs 0.25% (0.20-0.32%), P=0.039 and3.25% (2.48-3.46%) vs 1.70% (1.45-2.15%), P=0.001, respectively].Furthermore, the acromegalic patients had higher values for total lung mass in bothinspiratory and expiratory Q-MDCT [821 (635-923) vs 696 (599-769) g,P=0.021 and 844 (650-945) vs 637 (536-736) g, P=0.009,respectively]. In inspiratory Q-MDCT, TLV showed significant correlations with allFOT parameters. The TLV of hyperaerated areas showed significant correlations withintercept resistance (r_s=−0.602, P<0.001) and mean resistance(r_s=−0.580, P<0.001). These data showed that acromegalic patientshave increased amounts of lung tissue as well as nonaerated and poorly aerated areas.Functionally, there was a loss of homogeneity of the respiratory system. Moreover,there were correlations between the structural and functional findings of therespiratory system, consistent with the pathophysiology of the disease.     

Tranexamic acid in Neurosurgery: a controversy indication—review

Neurosurgical Review - Tranexamic acid (TXA) is one of the measures indicated to reduce bleeding and the need for volume replacement. However, data on risks and benefits are controversial. This...     

Management of prolactinomas in Brazil: an electronic survey

Dopamine agonists are the treatment of choice for prolactinomas. However, there are still controversies concerning dose, treatment duration and criteria for drug withdrawal in different clinical situations. The aim of this study was to assess diagnostic and therapeutic approaches to prolactinomas among members of the Brazilian Society of Endocrinology and Metabolism (SBEM). SBEM members answered a questionnaire sent by e-mail that included 18 questions related to controversial issues about the management of prolactinomas. Among SBEM members, 721 (approximately 24% of total) answered the questionnaire. Concerning the diagnosis, 38% of the respondents stated that prolactin levels < 100 ng/ml would exclude the presence of a prolactinoma. Most of them favored the screening for macroprolactin in asymptomatic individuals instead of a routine screening (74% vs. 26%). Regarding the treatment, 70% of the respondents chose cabergoline as the drug of choice to treat macroprolactinomas whereas similar proportions advised cabergoline or bromocriptine as the best treatment for microprolactinomas (52% vs. 48%). Only 20% and 34% of respondents favored treatment withdrawal 2–3 years after prolactin normalization in patients with macroprolactinomas and microprolactinomas, respectively. In case of pregnancy, only 58 and 70% of respondents advocated discontinuation of treatment with dopamine agonists in patients with macroprolactinomas and microprolactinomas, respectively. Finally, only 36% would allow breast-feeding without restriction, 44% would restrict it to patients with microprolactinomas and 20% would not recommend it for women with prolactinomas There are several points of disagreement among SBEM members regarding the management of prolactinomas.     

Effects of Risperidone on Cytokine Profile in Drug-Na?ve First-Episode Psychosis

Background:

There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder.

Methods:

The aim of this study is to compare cytokine levels (IL-2, IL-10, IL-4, IL-6, IFN-γ, TNF-α, and IL-17) in drug-naïve FEP patients both before and after treatment with risperidone for 10 weeks, and to investigate possible associations between cytokine levels and clinical responses to treatment and presence of depressive symptoms. It this study, we included 55 drug-naïve FEP patients who had repeated measurements of cytokine levels and 57 healthy controls.

Results:

We found that FEP patients had significantly higher IL-6, IL-10 and TNF-α levels than healthy controls. After risperidone treatment, these three cytokines and additionally IL-4 decreased significantly. No significant difference was found between the post-treatment cytokine levels in FEP patients and in healthy controls, suggesting that these alterations in cytokine profiles are a state marker of FEP. No significant association was found between risperidone-induced changes in cytokines and the clinical response to treatment or the presence of depression. There was a significant inverse association between the risperidone-induced changes in IL-10 and the negative symptoms.

Conclusions:

In conclusion, our results show a specific cytokine profile in FEP patients (monocytic and regulatory T-cell activation) and suggest immunoregulatory effects of risperidone treatment, characterized by suppressant effects on monocytic, Th2, and T-regulatory functions.     

Internal auditory canal hypoplasia associated with bilateral vestibulocochlear nerve aplasia and deviant facial nerve course: A case report and MRI findings

The evaluation of internal auditory canals and cochlea has gained significant importance due to the increasing number of cochlear implantations worldwide. This region’s anatomical study is essential for cochlear implant surgery using magnetic resonance imaging as the method of choice. We report a case of a 6-year-old male patient diagnosed with a rare bilateral malformation of the internal auditory canals associated with an aberrant course of the facial nerve and vestibulocochlear nerve aplasia. This report raises the importance of identifying this rare malformation for appropriate management and reinforces awareness of possible complications.