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Karen Bartlett

Publications and source records attributed to Karen Bartlett.

8 recordsLinked to original sources

Assessing the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B following the administration of Abelcet and AmBisome in combination with caspofungin to rats infected with Aspergillus fumigatus.

The purpose of this study was to assess the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B (AmpB) following the administration of Abelcet and AmBisome alone and in combination with Caspofungin to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (2.1-2.5 x 10(7) colony forming units [CFU]) was injected via the jugular vein; 48 h later male albino Sprague-Dawley rats (350-400 g) were administered either a single intravenous (i.v.) dose of Abelcet (5 mg AmpB/kg; n = 6), AmBisome (5 mg AmpB/kg; n = 6), Caspofungin (3 mg/kg; n = 5), Abelcet (5 mg AmpB/kg) plus Caspofungin (3 mg/kg) (n = 6), AmBisome (5 mg AmpB/kg) plus Caspofungin (3 mg/kg) (n = 7), or physiologic saline (non-treated controls; n = 6) once daily for 4 days. Antifungal activity was assessed by organ CFU concentrations and plasma galactomannan levels. Plasma and tissue samples were taken from each animal for AmpB pharmacokinetic analysis and tissue distribution determinations. Abelcet treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 73% compared to non-treated controls. Ambisome treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 69% compared to non-treated controls. Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 80% compared to non-treated controls. Abelcet plus Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 81% compared to non-treated controls. Ambisome plus Caspofungin treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 98% compared to non-treated controls. Abelcet treatment significantly decreased plasma galactomannan levels by 50 and 75% 96 h following the initiation of treatment in the absence and presence of Caspofungin co-therapy, respectively. AmBisome treatment significantly decreased plasma galactomannan levels by 73 and 78% 96 h following the initiation of treatment in the absence and presence of Caspofungin co-therapy, respectively. Co-administration of Caspofungin with Abelcet and AmBisome did not significantly alter the plasma concentration-time profile, pharmacokinetic parameters, and tissue distribution of AmpB. Taken together, our findings suggest that an alternative mechanism, possibly at the cellular level rather than altered AmpB disposition, may be an explanation for the differences in organ CFU concentrations following Abelcet plus Caspofungin versus AmBisome plus Caspofungin administration.

Amphotericin B↗

History and results of the two inter-laboratory round robin endotoxin assay studies on cotton dust.

BACKGROUND: In the US cotton industry, airborne cotton dust levels are regulated, and other countries are moving to specify safety limits for airborne endotoxins. There is concern about potential respiratory health hazards associated with agricultural and other organic dusts. In laboratories, ranking which samples have high and low levels of endotoxin is usually in good agreement between laboratories. When different laboratories assay identical samples, the levels differ. The objective of this research was to evaluate the intra- and inter-laboratory variability for 13 laboratories measuring endotoxin in cotton dust. METHOD: Two inter-laboratory round robin endotoxin assay studies were conducted using cotton dust. In the first round robin, each laboratory used their normal in-house assay method and then used a common extraction protocol. In the second round robin, a common extraction protocol and endotoxin assay kit was used. RESULTS: The intra-laboratory results had small variations but inter-laboratory results had very high variations. The inter-laboratory results using a common extraction protocol showed reduced differences. Using the same extraction protocol and endotoxin assay kit, the intra-laboratory variation was small and inter-laboratory variation was reduced but not enough for inter-laboratory agreement. Most of the laboratories were able to discern between the high and low endotoxin concentration dusts. CONCLUSIONS: Standardization has reduced the differences in results between laboratories and possibly further standardization may bring closer inter-laboratory agreement.

Air Microbiology↗

Cotton dust and endotoxin levels in three Shanghai textile factories: a comparison of samplers.

The results of a field survey at three Shanghai textile factories were used to compare the performance of the Chinese dust sampler (CDS) with the standard American sampler, vertical elutriator (VE). Side-by-side samples using a CDS and a VE were collected in seven specific manufacturing processes, with additional area and personal samples collected with a modified Institute of Occupational Medicine (IOM) personal inhalable sampler. Filters were analyzed for mass and endotoxin concentration. The geometric mean (GM) of the samples collected by the CDS was 0.79 mg/m3 (geometric standard deviation [GSD] 1.9) compared with a GM of 0.31 mg/m3 (GSD 1.7) for the VE measurements. The correlation coefficient for the CDS and VE samples was 0.35. The CDS, a high-volume total dust area sampler, collects 2 to 10 times more dust than the VE, a size-selective method, depending on the manufacturing process. In spinning at Factory A, the VE and CDS measured concentrations of 0.15 mg/m3 and 1.62 mg/m3, respectively. Cotton dust concentration measurements collected by the IOM sampler demonstrated that personal exposure concentrations were significantly higher (GM 1.84 mg/m3, GSD 1.6) than fixed-position area samples (GM 0.68 mg/m3, GSD 1.9). The endotoxin concentration based on the VE samples was 366 EU/m3, with the highest levels found in the specific manufacturing process drawing (1871 EU/m3) and the lowest in spinning (43.5 EU/m3). The results of the field comparison were used to convert historic CDS data into comparable exposures and to assign retrospective exposures to subjects included in a case-cohort study of lung cancer among female textile workers in Shanghai.

Air Pollutants, Occupational↗

Assessing the antifungal activity and toxicity profile of amphotericin B lipid complex (ABLC; Abelcet) in combination with caspofungin in experimental systemic aspergillosis.

The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B lipid complex (ABLC; Abelcet) following co-administration of Caspofungin to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (1.3-2.3 x 10(7) colony forming units [CFU]) was injected via the jugular vein; 48 h later male albino Sprague-Dawley rats (350-400 g) were administered either a single intravenous (i.v.) dose of Fungizone(R) (1 mg AmpB/kg), ABLC (1 or 5 mg AmpB/kg), or an equivalent volume of normal saline (NS) (vehicle control) once daily for 4 days. Rats were further randomized into groups to receive 3 mg/kg Caspofungin or physiologic saline i.v. once daily for 4 days. To assess antifungal activity, brain, lung, heart, liver, spleen, and kidney sections were homogenized with NS (2 mL; 1 g of each tissue/mL) and a 0.1-mL aliquot was spread plated onto a Sabouraud dextrose agar plate. The plates were incubated for 48 h at 37 degrees C, at which time the numbers of CFU were determined and corrected for tissue weight. To assess renal and hepatic toxicity, serum creatinine and aspartate aminotransferase levels were determined. Fungizone and ABLC at a dosing regimen of 1 mg/kg i.v. once daily for four consecutive days and Caspofungin at a dosing regimen of 3 mg/kg i.v. once daily for four consecutive days had similar effectiveness in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to non-treated controls. A combination of ABLC (1 mg/kg i.v. x 4 days) and Caspofungin (3 mg/kg i.v. x 4 days) significantly decreased the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to Caspofungin alone and non-treated controls. ABLC at a dosing regiment of 5 mg/kg i.v. once daily for four consecutive days was more effective in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to Fungizone or ABLC alone at 1 mg/kg and Caspofungin alone at 3 mg/kg. However, a combination of ABLC (5 mg/kg i.v. x 4 days) and Caspofungin (3 mg/kg i.v. x 4 days) was not more effective than ABLC at 5 mg/kg or the combination of ABLC at 1 mg/kg and Caspofungin 3 mg/kg in reducing the total number of Aspergillus fumigatus CFUs compared to controls. Except for non-treated infected control rats, none of the treatment groups tested displayed a greater than 50% increase in serum creatinine concentrations from baseline. In addition, only ABLC at a dosing regimen of 1 mg/kg i.v. once daily for four consecutive days displayed a greater than 50% increase in AST concentration from baseline. Taken together, these findings suggest that ABLC at 5 mg/kg once daily x 4 days appears to be the best therapeutic choice in this animal model.

Amphotericin B↗

Heat-treated Fungizone retains amphotericin B antifungal activity without renal toxicity in rats infected with Aspergillus fumigatus.

PURPOSE: The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus. METHODS: Infected rats were administered FZ and HFZ at a dosing regimen of 1 mg/kg i.v. once daily for 4 consecutive days. Following administration the number of colony forming units (CFUs) of Aspergillus fumigatus in different organs and serum creatinine concentrations were determined. RESULTS: FZ and HFZ had similar overall effectiveness in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to controls. Except for the serum creatinine concentrations reported in the nontreated infected control rats, none of the treatment groups tested displayed a greater than 50% increase in serum creatinine. CONCLUSIONS: Taken together, these findings suggest that HFZ at 1 mg/kg once daily x 4 days appears to be as effective as FZ as an antifungal agent without renal toxicity.

Amphotericin B↗

Effect of heat-treated amphotericin B on renal and fungal cytotoxicity.

The purpose of this investigation was to determine the cytotoxicity of amphotericin B (AMB; trade name Fungizone [FZ]) following the administration of FZ and a heat-treated form of FZ (HFZ) to LLC-PK(1) pig kidney cells and Cryptococcus neoformans var. gattii cells. HFZ was significantly less toxic to kidney cells than FZ at all concentrations tested. For both FZ and HFZ, the concentration range which resulted in a 50% reduction of the growth of fungal cells was 0.125 to 1 mg/ml. These findings suggest that heat treatment decreases AMB's renal cytotoxicity without modifying its antifungal activity.

Amphotericin B↗

Second inter-laboratory study comparing endotoxin assay results from cotton dust.

Previously, a large two-part inter-laboratory round robin endotoxin assay study was completed. This first study showed that when cotton dust samples, which are practically identical, are assayed for endotoxin that the intra- laboratory results had a very small variation while intra-laboratory results of the sample had a very high variation. In the first part of the study, each laboratory followed its own in-house assay protocol; but in the second part of the study, when the extraction protocol was standardized, the inter-laboratory results showed a lower variation, which suggested that with further standardization, further reduction of differences between laboratories might be achieved in order that results between laboratories would become more comparable. The results stimulated interest in extending the study to include cotton dust with two levels of endotoxin, standardization of the extraction protocol, and using the same assay kit from the same production lot. The results of this second round robin endotoxin assay study indicate that differences between laboratories are still high, but most of the laboratories could discern the cotton dusts with the different levels of endotoxin.

Chemistry Techniques, Analytical↗

Canada: an external quality review process--the Wellspring model.

Wellspring is a group of cancer support centers in Ontario, Canada. The centers provide information, support, and coping-skills programs for people with cancer and their families. To ascertain that all centers provide the same high quality of programs, the board at Wellspring established a panel of external oncology experts and asked them to establish a process to review program quality in each center. This article outlines the process undertaken to provide quality improvement in a nonprofit charitable organization.

Accreditation↗