Publications by authors named "John Bacher"

Battery technology has attained a key position as an energy storage technology in decarbonization of energy systems. Lithium-ion batteries have become the dominant technology currently used in consumer appliances, electric vehicles (EVs), and industrial applications. However, lithium-ion batteries are not alike and can have different cathode chemistries which makes their recycling more complex.

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galactomannan antigenemia is an accepted tool for the diagnosis of invasive pulmonary aspergillosis (IPA) in neutropenic patients. Little is known, however, about the utility of this biomarker to assess the efficacy of antifungal therapies. The pharmacokinetics (PK) and pharmacodynamics (PD) of posaconazole in treatment and prophylaxis were investigated in the persistently neutropenic rabbit model of IPA at doses between 2 and 20 mg/kg per day.

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Hematogenous meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeability and low cerebrospinal fluid (CSF) concentrations, but is effective in treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized that AmB may achieve focally higher concentrations in infected CNS lesions.

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The removal of sulfidic species in tailings using froth flotation is a promising approach to prevent phenomena such as acid mine drainage. However, flotation requires the consumption of reagents and water that represent additional expenses. Despite the strong interest of scientists and industry alike on tailings remediation, there is no study on the minimization of resource consumption to promote the implementation of desulfurization with froth flotation.

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Biomedical translational research frequently incorporates collection of CSF from NHP, because CSF drug levels are used as a surrogate for CNS tissue penetration in pharmacokinetic and dynamic studies. Surgical placement of a CNS ventricular catheter reservoir for CSF collection is an intensive model to create and maintain and thus may not be feasible or practical for short-term studies. Furthermore, previous NHP lumbar port models require laminectomy for catheter placement.

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Purpose: To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints.

Materials And Methods: Rabbit Vx2 liver tumors were embolized with 100-300-μm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint.

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Purpose: To evaluate the effect of embolic diameter on achievement of hypoxia after embolization in an animal model of liver tumors.

Materials And Methods: Inoculation of VX2 tumors in the left liver lobe was performed successfully in 12 New Zealand white rabbits weighing 3.7 kg ± 0.

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Galactomannan and (1→3)-β-D-glucan are useful biomarkers of invasive pulmonary aspergillosis (IPA). However, the effects of immunosuppression on levels of galactomannan or (1→3)-β-D-glucan in IPA are not well understood or quantified. We therefore studied the simultaneous levels of galactomannan and (1→3)-β-D-glucan in two rabbit models of experimental IPA: (1) AraC-induced neutropenia in untreated (UC-AraC) and liposomal amphotericin B-treated (LAMB-AraC) rabbits; and (2) nonneutropenic cyclosporine-methylprednisolone immunosuppression in untreated (UC-CsA+M) and LAMB-treated (LAMB-CsA+M) rabbits.

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Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection.

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Aneurismal subarachnoid hemorrhage (SAH) is relatively rare form of hemorrhagic stroke, which produces significant social and medical challenges. As it affects people in their high productivity age and leaves 50 % of them dead and almost 70 % of survivors disabled, many of them severely, the reasons of such a dismal outcome have been intensively researched all over the world. Nevertheless, despite more than a half a century of clinical and scientific effort and dramatic improvement of surgical repair of aneurysms, the causes of poor outcome remain enigmatic.

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Pediatric diffuse intrinsic pontine gliomas are aggressive brainstem tumors that fail to respond to treatment. We hypothesize that the protective features of the pons may hinder chemotherapeutic agents from entering pontine tissue compared with cortical brain tissue. To test this hypothesis, we developed a unique nonhuman primate model using microdialysis, a continuous in vivo extracellular sampling technique, to compare drug exposure concurrently in pontine tissue, cortical tissue, CSF, and plasma after intravenous administration of chemotherapeutic agents.

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Members of the order Mucorales are emerging invasive molds that cause infections in immunocompromised patients. However, little is known about the relation between different species of Mucorales and their virulence in invasive pulmonary mucormycosis. Based upon our earlier epidemiological studies, we hypothesized that Cunninghamella bertholletiae would demonstrate increased virulence.

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We demonstrated that sodium gluconate was the factor causing false-positive galactomannan (GM) antigenemia of Plasma-Lyte hydration solution. Infusion of sodium gluconate-containing solution but not gluconate-free Plasma-Lyte resulted in positive serum GM antigenemia. Serum GM concentrations also correlated with the volume and in vitro concentrations of GM within gluconate-containing solutions of infused Plasma-Lyte.

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Diagnosis of invasive pulmonary aspergillosis (IPA) remains a major challenge to clinical microbiology laboratories. We developed rapid and sensitive quantitative PCR (qPCR) assays for genus- and species-specific identification of Aspergillus infections by use of TaqMan technology. In order to validate these assays and understand their potential diagnostic utility, we then performed a blinded study of bronchoalveolar lavage (BAL) fluid specimens from well-characterized models of IPA with the four medically important species.

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In this study we compared rat (n = 16) responses to euthanasia with either gradual-fill CO(2) or rapid induction argon gas by evaluating the animals' heart rate via radiotelemetry, behavior, and vocalizations. We also evaluated the histologic effects of the gases. Rats were placed in an open test chamber 24 h before the start of the experiment.

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Acute invasive pulmonary aspergillosis is a rapidly progressive and frequently lethal infection. Relatively little is known about early events in the pathogenesis and relationship between the cell wall biomarkers galactomannan and (1→3)-β-d-glucan. The consequences of delayed antifungal therapy are also poorly defined.

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Purpose: Cisplatin, carboplatin, and oxaliplatin are chemically reactive anticancer drugs with modest activity in brain tumors. Previously, we have demonstrated that drug exposure in cerebrospinal fluid (CSF) for these platinum analogs is <5% of the plasma ultrafiltrate (UF) drug exposure in nonhuman primates. Microdialysis is a minimally invasive in vivo method for sampling small molecules in the blood and tissue extracellular fluid (ECF).

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We studied the antifungal activity of anidulafungin (AFG) in combination with voriconazole (VRC) against experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits and further explored the in vitro and in vivo correlations by using Bliss independence drug interaction analysis. Treatment groups consisted of those receiving AFG at 5 (AFG5 group) and 10 (AFG10 group) mg/kg of body weight/day, VRC at 10 mg/kg every 8 h (VRC group), AFG5 plus VRC (AFG5+VRC group), and AFG10 plus VRC (AFG10+VRC group) and untreated controls. Survival throughout the study was 60% for the AFG5+VRC group, 50% for the VRC group, 27% for the AFG10+VRC group, 22% for the AFG5 group, 18% for the AFG10 group, and 0% for control rabbits (P < 0.

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Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are caused by organism-mediated tissue injury, vascular invasion, and hemorrhagic infarction. Ultrafast computed tomography (UFCT) scanning reproducibly measures these lesions in experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. The pulmonary lesion score from UFCT scanning is a useful outcome variable for measuring differences in efficacy of antifungal compounds alone and in combination, as well as the virulence of different strains and species of Aspergillus.

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We developed two real-time quantitative PCR (qPCR) assays, targeting the 28S rRNA gene, for the diagnosis of zygomycosis caused by the most common, clinically significant Zygomycetes. The amplicons of the first qPCR assay (qPCR-1) from Rhizopus, Mucor, and Rhizomucor species were distinguished through melt curve analysis. The second qPCR assay (qPCR-2) detected Cunninghamella species using a different primer/probe set.

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The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1-->3)-beta-D-glucan (beta-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.

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Background: Hematogenous Candida meningoencephalitis (HCME) is a relatively frequent manifestation of disseminated candidiasis in neonates and is associated with significant mortality and neurodevelopmental abnormalities. The outcome after antifungal therapy is often suboptimal, with few therapeutic options. Limited clinical data suggest that echinocandins may have role to play in the treatment of HCME.

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Background: Little is known about the pathogenesis of invasive pulmonary aspergillosis and the relationship between the kinetics of diagnostic markers and the outcome of antifungal therapy.

Methods: An in vitro model of the human alveolus, consisting of a bilayer of human alveolar epithelial and endothelial cells, was developed. An Aspergillus fumigatus strain expressing green fluorescent protein was used.

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Brain [2-(13)C]gamma-aminobutyric acid (GABA) signal derived from the glia-specific substrate [2-(13)C]acetate reflects the extent of the GABA-glutamine neurotransmitter cycling between GABAergic neurons and glial cells. We report, for the first time, in vivo quantification of the GABA-glutamine cycling flux. The GABA-glutamine cycling flux rate was determined to be 1.

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We investigated the compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to seven noninfected, catheterized rabbits received 1 mg of amphotericin B deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung tissue were obtained.

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