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Biomedical subjects

Thomas Moore

Publications and source records attributed to Thomas Moore.

7 recordsLinked to original sources

Salvage treatment of histoplasmosis with posaconazole.

Six patients received salvage treatment with posaconazole oral suspension (800 mg/day in divided doses) for severe forms of histoplasmosis. One patient had pulmonary disease and 5 had disseminated disease. Previous antifungal therapy consisted of amphotericin B, itraconazole, fluconazole, or voriconazole. Posaconazole treatment duration for individual patients ranged from 6 weeks to 34 weeks. All patients had successful clinical outcomes with significant clinical improvements noted during the first month of therapy. Although the number of patients evaluated in this case series is small, the findings are encouraging and provide preliminary evidence that posaconazole may be a useful salvage treatment option for histoplasmosis involving a variety of infected tissues and organs.

Adolescent↗

Multidimensional proteomics of human serum using parallel chromatography of native constituents and microplate technology.

A versatile, multidimensional, and non-denaturing proteome separation procedure using microplate technology is presented, yielding a digitized image of proteome composition. In the first dimension, the sample under study is separated into 96 fractions by size exclusion chromatography (SEC). In the second dimension, the fractions of the first dimension are transferred by the liquid-handling device CyBi-Well (CyBio AG, Jena, Germany) to 96 parallel anion exchange chromatography columns. In this way the proteins are conserved in their native states and are distributed in 2400 liquid fractions with high recovery rates and sufficient reproducibility. The resulting fractions are subjected to protein quantitation and identification. Spectrophotometrical and immunological methods and enzyme activity measurements are used for quantitation. To identify proteins, the fractions are subjected to MALDI-MS, and their tryptic digests to both MALDI- and LC-ESI-MS/MS. All preparation steps except the first are applied in parallel to sets of multiples of 96 samples. The procedure may be refined by adding more separation steps and may be adapted to various protein amounts and to various proteomes. Moreover, the method offers the opportunity to investigate functional protein complexes. The method was applied to separate the normal human serum proteome. Within 255 fractions exhibiting the highest protein concentrations, 742 proteins were identified by LC-ESI-MS/MS peptide sequence tags.

Blood Proteins↗

Phase II, randomized, double-blind, multicenter study comparing the safety and pharmacokinetics of tefibazumab to placebo for treatment of Staphylococcus aureus bacteremia.

Tefibazumab (Aurexis), a humanized monoclonal antibody that binds to the surface-expressed adhesion protein clumping factor A, is under development as adjunctive therapy for serious Staphylococcus aureus infections. Sixty patients with documented S. aureus bacteremia (SAB) were randomized and received either tefibazumab at 20 mg/kg of body weight as a single infusion or a placebo in addition to an antibiotic(s). The primary objective of the study was determining safety and pharmacokinetics. An additional objective was to assess activity by a composite clinical end point (CCE). Baseline characteristics were evenly matched between groups. Seventy percent of infections were healthcare associated, and 57% had an SAB-related complication at baseline. There were no differences between the treatment groups in overall adverse clinical events or alterations in laboratory values. Two patients developed serious adverse events that were at least possibly related to tefibazumab; one hypersensitivity reaction was considered definitely related. The tefibazumab plasma half-life was 18 days. Mean plasma levels were <100 microg/ml by day 14. A CCE occurred in six patients (four placebo and two tefibazumab patients) and included five deaths (four placebo and one tefibazumab patient). Progression in the severity of sepsis occurred in four placebo and no tefibazumab patients. Tefibazumab was well tolerated, with a safety profile similar to those of other monoclonal antibodies. Additional trials are warranted to address the dosing range and efficacy of tefibazumab.

Adult↗

Prospective observational study to establish predictors of glyburide success in women with gestational diabetes mellitus.

OBJECTIVE: To establish parameters associated with therapeutic success in gestational diabetics treated with glyburide. STUDY DESIGN: A total of 69 gestational diabetics who failed dietary therapy were treated with glyburide. Inadequate glycemic control on maximum dose glyburide (10 mg b.i.d.) was considered treatment failure. The glyburide failure rate was calculated and factors that might predict success with glyburide were analyzed between the success and failure groups using chi(2) or Student'st-tests. RESULTS: The glyburide failure rate was 18.8%. Gestational age at glyburide initiation (p<0.01), pretreatment fasting blood sugars (p<0.001), and 1-hour postprandial values (p<0.001) were the only statistically significant factors between the two groups. Glyburide success was predicted if dietary failure occurred after 30 weeks, or fasting blood sugars were <110 mg/dl and 1-hour postprandials were <140 mg/dl (sensitivity 98%, specificity 65%). CONCLUSION: Gestational diabetics who fail dietary therapy after 30 weeks gestation or have fasting blood sugars <110 mg/dl and 1-hour postprandials <140 mg/dl do well on glyburide therapy.

Adult↗

An improved method for checking HTS/uHTS liquid-handling systems.

An efficient method is presented to determine precision and accuracy of multichannel liquid-handling systems under conditions near to application. The method consists of gravimetrical determination of accuracy and optical determination of precision based on the dilution of absorbing and fluorescent dye solutions in microplates. Mean delivery volume per well can be determined with precision better than a 0.04% coefficient of variation (CV). Optical signal precision, CV(S), is improved by multiwavelength measurements. Precision of absorbance measurement yields a better resolution than precision of fluorescence measurement (0.3% and 1.5%, respectively), indicating that absorbance measurements should be preferred. From CV(S), an upper bound of the precision of the volumes delivered is derived. Method performance is demonstrated with the dispenser CyBi-Drop and the pipettor CyBi-Well using different ejection principles; with commonly used fluids; with 96-, 384-, and 1536-well microplates; and with photometric and fluorometric indicators. Precision of the volumes delivered, as obtained with optimized methods, all plate formats, and both devices, is better than 2% CV with 2 microL set volume and about 1% CV with higher set volumes.

Calibration↗

Prenatal evaluation of facial clefts with two-dimensional and adjunctive three-dimensional ultrasonography: a prospective trial.

OBJECTIVE: The purpose of this study was to compare the prenatal diagnostic capabilities of two-dimensional ultrasonography versus adjunctive three-dimensional ultrasonography for fetal cleft lip and palate. STUDY DESIGN: Fetuses that were suspected of a facial cleft were then examined sequentially with two-dimensional ultrasonography then with a targeted scan of the fetal face with three-dimensional ultrasonography. The images were coded as cleft, no cleft, or equivocal for lip and palate. Postnatal outcome follow-up was obtained. RESULTS: Fifty-three of 57 fetuses had outcome results available. The diagnostic accuracy (true positive + true negative) of adjunct three-dimensional ultrasonography versus two-dimensional ultrasonography alone were improved for cleft lip (100% [53/53 fetuses] vs 91% [48/53 fetuses], P <.05) and cleft palate (89% [47/53 fetuses] vs 57% [30/53 fetuses], P <.05) CONCLUSION: There is significant improvement in diagnostic accuracy with two-dimensional ultrasonography with adjunctive three-dimensional ultrasonography compared with two-dimensional ultrasonography alone for the prenatal evaluation of facial clefts.

Cleft Lip↗

Supracondylar femur fracture fixation: mechanical comparison of the 95 degrees condylar side plate and screw versus 95 degrees angled blade plate.

The best way to stabilize supracondylar femur fractures remains debatable. Previous studies have compared internal fixation to intramedullary fixation, but none have compared the stiffness characteristics and strength of the 95 degrees angled blade plate (ABP) with the 95 degrees condylar side plate and screw (DCS). 14 synthetic femora were cut in half and the proximal pole of the distal fragment was made secure. A 1 cm gap was made parallel to the femoral condylar weight-bearing surface to create an extraarticular supracondylar femur fracture (OTA 33-A3). 7 femora were stabilized with an ABP and 7 with a DCS. Using an MTS compression/torsion servohydraulic testing machine, each femur was tested in 7 modes of loading: (1) axial compression; (2) anterior compression; (3) posterior compression; (4) medial compression; (5) lateral compression; (6) torsion in external rotation; and (7) torsion in internal rotation. The stiffness of the construct in each mode, the "maximum load in axial compression", and the fatigue characteristics in axial compression were measured. The DCS showed a statistically significant greater stiffness in axial compression and average maximal load than the ABP. The fatigue tests revealed no evidence of permanent deformation or loosening of either construct.

Biomechanical Phenomena↗