Testing simultaneously different covariance block diagonal structures - the multi-sample case.

In this work a likelihood ratio test which allows to test simultaneously if, several covariance matrices are equal and block diagonal with different specific structures in the diagonal blocks, is developed. The distribution of the likelihood ratio statistic is studied and the expression of its hth null moment are derived. In order to make the test useful in practical terms, near-exact approximations are developed for the likelihood ratio statistic. A practical application to real data set together with numerical studies and simulations are provided in order illustrate the applicability of the test and also to assess the precision of the near-exact approximations developed.

The Effect of Inadequate Presample Blood Volume Withdrawal from Intravenous Catheter and Extension Sets on Measured Circulating L-Blood Lactate Concentration in Horses Receiving Lactated Ringer's Solution.

BACKGROUND: Circulating l-lactate concentration is commonly measured in hospitalized horses by sampling from indwelling intravenous (IV) catheters. However, there are no published evidence-based recommendations to prevent contamination by lactated Ringer's solution (LRS). HYPOTHESIS: Withdrawing 10 mL of blood from the LRS-containing extension set connected to the IV catheter before obtaining the sample for analysis should be adequate to obtain accurate measurement of blood lactate concentration (BLC). ANIMALS: Thirty-three adult hospitalized horses receiving constant rate infusion of LRS. METHODS: Immediately after disconnecting the LRS, 5 sequential 5 mL blood samples were obtained by aspiration from an extension set connected to an indwelling IV catheter, followed by 3 samples collected by direct venipuncture of the contralateral jugular vein. Samples were analyzed with 1 portable blood lactate analyzer. A linear mixed model was used to examine differences in lactate concentrations among samples collected from the catheter and by direct venipuncture. RESULTS: After considering differences in age, breed, sex, and reason for hospitalization, BLCs were higher (P < .001) in the first and second 5 mL samples collected through the extension set/catheter than in all other extension set/catheter samples or the direct venipuncture samples. The largest difference observed between the third and subsequent catheter or venipuncture samples was 0.34 mmol/L with an upper 95% CI of 1.12 mmol/L. CONCLUSIONS AND CLINICAL IMPORTANCE: Withdrawing 15 mL of blood from a LRS-containing extension set connected to an IV catheter (5.9 mL total volume capacity) before obtaining the sample for blood lactate analysis is suggested to optimize accuracy of BLC measurements.

Ciprofloxacin shows synergism with classical antifungals against Histoplasma capsulatum var. capsulatum and Coccidioides posadasii.

This study evaluated the in vitro interaction between ciprofloxacin (CIP) and classical antifungals against Histoplasma capsulatum var. capsulatum in mycelial (n = 16) and yeast-like forms (n = 9) and Coccidioides posadasii in mycelial form (n = 16). This research was conducted through broth microdilution and macrodilution, according to Clinical Laboratory Standards Institute. Inocula were prepared to obtain from 0.5 × 10(3) to 2.5 × 10(4) cfu ml(-1) for H. capsulatum and from 10(3) to 5 × 10(3) cfu ml(-1) for C. posadasii. Initially, minimum inhibitory concentration (MIC) for each drug alone was determined. Then, these MICs were used as the highest concentration for each drug during combination assays. The procedures were performed in duplicate. For all combination assays, MICs were defined as the lowest concentration capable of inhibiting 80% of visible fungal growth, when compared to the drug-free control. Drug interaction was evaluated by paired sample t-Student test. The obtained data showed a significant MIC reduction for most tested combinations of CIP with antifungals, except for that of CIP and voriconazole against yeast-like H. capsulatum. This study brings potential alternatives for the treatment of histoplasmosis and coccidioidomycosis, raising the possibility of using CIP as an adjuvant antifungal therapy, providing perspectives to delineate in vivo studies.

Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B.

The Cryptococcus neoformans species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole-trimethoprim (SMX/TMP) and sulfadiazine-pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of C. neoformans and C. gattii. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of C. neoformans (n = 15) and C. gattii (n = 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of Cryptococcus spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in C. neoformans and C. gattii planktonic cells. Our results highlight the antifungal potential of antifolate drugs.

Evaluation of renal and hepatic functions in dogs naturally infected by visceral leishmaniasis submitted to treatment with meglumine antimoniate.

The present study aimed to evaluate the renal and hepatic responses in eight dogs with visceral leishmaniasis submitted to treatment with meglumine antimoniate and to verify the occurrence of possible side effects. Urinalysis, hepatic and renal function tests were carried out in all animals at up to seven moments. After the end of a six-month observation period, all dogs were euthanized. Before the beginning of the experiment urinary and biochemical alterations were observed in four dogs due to the changes caused by the parasite itself. These alterations included the presence of renal cells, cylindruria, proteinuria, azotemia, hyperproteinemia and hypoalbuminemia. One dog died on the third day after treatment because an aggravation of the clinical picture, probably due to the medication. During the course of the study, an increase in hepatic enzymes was verified in two animals. Sixty days after the beginning of the treatment four dogs showed remission of clinical signs. The other three were asymptomatic with persistent biochemical alterations. From these, two presented recurrence of clinical signs about 150 days after the beginning of the treatment while in the other, hyperproteinemia persisted. Meglumine antimoniate was not efficient to treat dogs with severe renal dysfunction and the side effects observed were pain at the site of injection and the probable transient hepatotoxicity, evidenced by biochemical examinations, but without the presence of clinical signs.