Juan Carlos Martínez

Comparative Study of the Effects of Pyridoxine, Rifampin, and Renal Function on Hematological Adverse Events Induced by Linezolid

ABSTRACT Hematological disturbances that develop during linezolid treatment are a major concern when linezolid is administered for prolonged periods of time. The aim of this study was to evaluate the influences of pyridoxine, rifampin, and renal function on hematological adverse events. From January 2002 to April 2006, 52 patients received a long-term course of linezolid. Blood cell counts were monitored weekly. Thrombocytopenia was defined as a decrease to <75% of the baseline platelet count, and anemia was defined when the hemoglobin concentration decreased by ≥2 g/liter from the baseline value. Twenty-four patients received linezolid alone, and 28 patients received linezolid plus 200 mg of pyridoxine. The Kaplan-Meier survival method, followed by the log-rank test, was used to estimate the cumulative probability of adverse events, and Cox regression analysis was performed to evaluate the independent predictors of toxicity. The baseline characteristics of the patients in both groups were similar. The cumulative probability of thrombocytopenia and anemia in patients who received pyridoxine was not different from that in patients who did not receive it. Hematological adverse events were less frequent in patients taking rifampin and were more frequent in patients with renal failure. However; the Cox regression analysis showed that rifampin was the only independent predictor associated with a lower risk of thrombocytopenia (hazard ratio, 0.37; 95% confidence interval, 0.14 to 0.98; P = 0.045). In conclusion, pyridoxine did not prevent linezolid-related hematological adverse events, and the coadministration of rifampin was associated with a lower risk of thrombocytopenia.

Amiodarone and Miltefosine Act Synergistically against Leishmania mexicana and Can Induce Parasitological Cure in a Murine Model of Cutaneous Leishmaniasis

ABSTRACT Leishmaniasis is parasitic disease that is an important problem of public health worldwide. Intramuscularly administered glucantime and pentostam are the most common drugs used for treatment of this disease, but they have significant limitations due to toxicity and increasing resistance. A recent breakthrough has been the introduction of orally administered miltefosine for the treatment of visceral, cutaneous, and mucocutaneous leishmaniasis, but the relative high cost and concerns about teratogenicity have limited the use of this drug. Searching for alternative drugs, we previously demonstrated that the antiarrhythmic drug amiodarone is active against Leishmania mexicana promastigotes and intracellular amastigotes, acting via disruption of intracellular Ca2+ homeostasis (specifically at the mitochondrion and the acidocalcisomes of these parasites) and through inhibition of the parasites de novo sterol biosynthesis (X. Serrano-Martín, Y. García-Marchan, A. Fernandez, N. Rodriguez, H. Rojas, G. Visbal, and G. Benaim, Antimicrob. Agents Chemother. 53:1403-1410, 2009). In the present work, we found that miltefosine also disrupts the parasites intracellular Ca2+ homeostasis, in this case by inducing a large increase in intracellular Ca2+ levels, probably through the activation of a plasma membrane Ca2+ channel. We also investigated the in vitro and in vivo activities of amiodarone and miltefosine, used alone or in combination, on L. mexicana. It was found that the drug combination had synergistic effects on the proliferation of intracellular amastigotes growing inside macrophages and led 90% of parasitological cures in a murine model of leishmaniasis, as revealed by a PCR assay using a novel DNA sequence specific for L. mexicana.

Superatomic Boolean Algebras Constructed from Morasses

By using the notion of a simplified (a, 1)-morass, we construct a-thin-tall, a-thin-thick and, in a forcing extension, K-very thin-thick superatomic Boolean algebras for every infinite regular cardinal a.

Usefulness of 99mTc-ciprofloxacin scintigraphy in the diagnosis of prosthetic joint infections.

ObjectiveTo evaluate the usefulness of 99mTc-ciprofloxacin scintigraphy (CFS) in patients with hip or knee arthroplasty and suspected infection. MethodsForty patients (26 women, 14 men) with a mean age of 66±10 years and local pain in the hip (21), knee (16), or shoulder (three) prosthesis were recruited. CFS was performed at 1, 4, and 24 h after intravenous injection of 370 MBq. Anterior and posterior views centered on the affected joint were performed in all patients. A routine bone scan, 99mTc-hexamethylpropyleneamine oxime leukocyte scan, and 99mTc-colloid scan [leukocyte scintigraphy–bone marrow scintigraphy (LS–MS)] were performed. Final diagnosis of infection was confirmed by positive microbiological analysis or macroscopic evidence of purulent material. ResultsDiagnosis of arthroplasty infection was established in 16 out 40 cases: coagulase-negative staphylococci (nine), Staphylococcus aureus (three), Enterococcus (one), and macroscopic infection in the remaining three cases. CFS imaging showed the 24-h image to be the best acquisition time-point. The sensitivity, specificity, negative predictive value, and positive predictive value for LS–MS were 75, 92, 86, and 85%, whereas for CFS at 24 h these figures were 88, 71, 67, and 89%. The sensitivity and specificity for LS–MS and for CFS at 24 h for hip were (74, 90, and 88, 85%) and for knee (83, 90 and 100, 50%). ConclusionCFS can be useful in the diagnosis of arthroplasty infection of the hip as a substitute for LS–MS. It is recommended that CFS images be obtained 24 h after injection. The lack of specificity of CFS makes this technique inadequate for knee prostheses in this series.

A consistency result on thin-very tall Boolean algebras

It was proved by Baumgartner and Shelah that Con (ZFC)→Con (ZFC + “there is a superatomic Boolean algebra of width ω and height ω2”). In this paper we improve Baumgartner-Shelah’s theorem, showing that Con (ZFC)→Con (ZFC+“for every α<ω3 there is a superatomic Boolean algebra of width ω and height α”).

A consistency result on thin-tall superatomic Boolean algebras

We probe that if κ is an infinite cardinal with κ <κ =κ, then there is a cardinal-preserving notion of forcing that forces the existence of a κ-thin-tall superatomic Boolean algebra. Consistency for specific κ, like ω 1 , then follows as a corollary

Superatomic Boolean algebras constructed from strongly unbounded functions

Using Koszmiders strongly unbounded functions, we show the following consistency result: Suppose that κ, λ are infinite cardinals such that κ++ + ≤ λ, κ<κ = κ and 2κ = κ+, and η is an ordinal with κ+ ≤ η < κ++ and cf(η) = κ+. Then, in some cardinal-preserving generic extension there is a superatomic Boolean algebra such that , for every α < η and (i.e., there is a locally compact scattered space with cardinal sequence 〈κ〉η⌢〈λ〉). Especially, and can be cardinal sequences of superatomic Boolean algebras.

On cardinal sequences of scattered spaces

Abstract It was proved by Dow and Simon that there are 2 ω 1 (as many as possible) pairwise nonhomeomorphic compact, T 2 , scattered spaces of height ω 1 and width ω. In this paper, we prove that if α is an ordinal with ω 1 ⩽ α ω 2 and θ = 〈 κ ξ : ξ α 〉 is a sequence of cardinals such that either κ ξ = ω or κ ξ = ω 1 for every ξ α , then there are 2 ω 1 pairwise nonhomeomorphic compact, T 2 , scattered spaces whose cardinal sequence is θ.

On uncountable cardinal sequences for superatomic Boolean algebras

The countable sequences of cardinals which arise as cardinal sequences of superatomic Boolean algebras were characterized by La Grange on the basis of ZFC set theory. However, no similar characterization is available for uncountable cardinal sequences. In this paper we prove the following two consistency results:(1)Ifθ = 〈κα :α <ω1〉 is a sequence of infinite cardinals, then there is a cardinal-preserving notion of forcing that changes cardinal exponentiation and forces the existence of a superatomic Boolean algebraB such that θ is the cardinal sequence ofB.(2)Ifκ is an uncountable cardinal such thatκ<κ =κ andθ = 〈κα :α <κ+〉 is a cardinal sequence such thatκα ≥κ for everyα <κ+ andκα =κ for everyα <κ+ such that cf(α)<κ, then there is a cardinal-preserving notion of forcing that changes cardinal exponentiation and forces the existence of a superatomic Boolean algebraB such that θ is the cardinal sequence ofB.

A consistency result on cardinal sequences of scattered Boolean spaces

We prove that if GCH holds and τ = 〈κα : α < η 〉 is a sequence of infinite cardinals such that κα ≥ |η | for each α < η, then there is a cardinal-preserving partial order that forces the existence of a scattered Boolean space whose cardinal sequence is τ. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)