Corinne Fantz | Emory University (original) (raw)

Papers by Corinne Fantz

Research paper thumbnail of Assessment of the Diagnostic Accuracy of the TDx-FLM II to Predict Fetal Lung Maturity

Clinical Chemistry, 2002

Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and r... more Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and rapid assessment of markers of fetal lung maturity is critical to clinicians in deciding whether to deliver a preterm infant. Our objective was to determine the optimal diagnostic cutoff value for the TDx-FLM II assay (Abbott Laboratories) for predicting clinically significant RDS. Methods: Amniotic fluid TDx-FLM II data were collected retrospectively over 4 years. Women were included in the study if they had delivered within 72 h of TDx-FLM II testing and both the mother and infant charts could be reviewed. Women who had been treated with steroids and delivered unaffected infants were excluded from the analysis. The diagnosis of RDS was defined as infants who either were treated with surfactant and/or were placed on a ventilator and/or required continuous positive airway pressure for >1 day. Results: A total of 185 women met all entry criteria (15 RDS, 170 non-RDS). A cutoff value for...

Research paper thumbnail of Where Are the Preanalytical Stability Standards?

The Journal of Applied Laboratory Medicine, 2018

Research paper thumbnail of Cirrhosis Originally Diagnosed as Nonalcoholic Steatohepatitis

Research paper thumbnail of Effectiveness of barcoding for reducing patient specimen and laboratory testing identification errors: A Laboratory Medicine Best Practices systematic review and meta-analysis

Clinical Biochemistry, 2012

Research paper thumbnail of Falsely Increased hCG in Patients with High Leukocyte Counts

Research paper thumbnail of Falsely Decreased Human Chorionic Gonadotropin (hCG) Results Due to Increased Concentrations of the Free   Subunit and the   Core Fragment in Quantitative hCG Assays

Clinical Chemistry, 2010

BACKGROUND Earlier studies have shown that increased concentrations of certain human chorionic go... more BACKGROUND Earlier studies have shown that increased concentrations of certain human chorionic gonadotropin (hCG) variants can cause false-negative results in some qualitative hCG devices. The objective of this study was to determine if increased concentrations of hCGβ and hCGβ core fragment (hCGβcf) cause falsely decreased results on 9 commercially available quantitative hCG assays. METHODS Several concentrations of purified hCGβ and hCGβcf were added to 2 sets of 6 serum samples with and without a fixed concentration of intact hCG. We examined 9 widely used immunoassays to measure immunoreactive hCG. Falsely decreased results were defined as those in which the measured hCG concentration was ≤50% of expected. RESULTS High concentrations of hCGβ (≥240 000 pmol/L) produced falsely decreased hCG measurements in 2 assays known to detect this variant. Similarly, high concentrations of hCGβcf (≥63 000 pmol/L) produced falsely decreased hCG measurements in 3 assays that do not detect puri...

Research paper thumbnail of Strategies for Evaluating Critical Value Limits: Opportunities for Saving Time and Money Without Compromising Care

Research paper thumbnail of Strategies for Evaluating Critical Value Limits: Opportunities for Saving Time and Money Without Compromising Care

Research paper thumbnail of Teaching Laboratory Medicine to Medical Students: Implementation and Evaluation

Archives of Pathology & Laboratory Medicine, 2012

Laboratory medicine is an integral component of patient care. Approximately 60% to 70% of medical... more Laboratory medicine is an integral component of patient care. Approximately 60% to 70% of medical decisions are based on laboratory results. Physicians in specialties that order the tests are teaching medical students laboratory medicine and test use with minimal input from laboratory scientists who implement and maintain the quality control for those tests. To develop, implement, and evaluate a 1.5-day medical student clinical laboratory experience for fourth-year medical students in their last month of training. The experience was devised and directed by laboratory scientists and included a panel discussion, laboratory tours, case studies that focused on the goals and objectives recently published by the Academy of Clinical Laboratory Physicians and Scientists, and medical-student presentations highlighting salient points of the experience. The same knowledge quiz was administered at the beginning and end of the experience and 84 students took both quizzes. A score of 7 or more was obtained by 16 students (19%) on the initial quiz, whereas 34 (40%) obtained the same score on the final quiz; the improvement was found to be statistically significant (P = .002; t = 3.215), particularly in 3 out of the 10 questions administered. Although the assessment can only measure a small amount of knowledge recently acquired, the improvement observed by fourth-year medical students devoting a short period to learning laboratory medicine principles was encouraging. This medical student clinical laboratory experience format allowed teaching of a select group of laboratory medicine principles in 1.5 days to an entire medical school class.

Research paper thumbnail of Thyroid Function during Pregnancy

Background: This Case Conference reviews the normal changes in thyroid activity that occur during... more Background: This Case Conference reviews the normal changes in thyroid activity that occur during pregnancy and the proper use of laboratory tests for the diagnosis of thyroid dysfunction in the pregnant patient. Case: A woman in the 18th week of pregnancy presented with tachycardia, increased blood pressure, severe vomiting, increased total and free thyroid hormone concentrations, a thyroid-stimulating hormone (TSH) concentration within the reference interval, and an increased human chorionic gonadotropin (hCG) ␤-subunit concentration. Issues: During pregnancy, normal thyroid activity undergoes significant changes, including a two-to threefold increase in thyroxine-binding globulin concentrations, a 30 -100% increase in total triiodothyronine and thyroxine concentrations, increased serum thyroglobulin, and increased renal iodide clearance. Furthermore, hCG has mild thyroid stimulating activity. Pregnancy produces an overall increase in thyroid activity, which allows the healthy individual to remain in a net euthyroid state. However, both hyper-and hypothyroidism can occur in pregnant patients. In addition, two pregnancy-specific conditions, hyperemesis gravidarum and gestational trophoblastic disease, can lead to clinical hyperthyroidism. The normal changes in thyroid activity and the association of pregnancy with conditions that can cause hyperthyroidism necessitates careful interpretation of thyroid function tests during pregnancy. Conclusion: Assessment of thyroid function during pregnancy should be done with a careful clinical evaluation of the patient's symptoms as well as measurement of TSH and free, not total, thyroid hormones. Measurement of thyroid autoantibodies may also be useful in selected cases to detect maternal Graves disease or Hashi-moto thyroiditis and to assess risk of fetal or neonatal consequences of maternal thyroid dysfunction.

Research paper thumbnail of Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and cranial nerves of a murine model of globoid cell leukodystrophy

Nmr in Biomedicine, 2009

Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of ... more Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactosylceramidase. In both human patients and the authentic murine Twitcher model, pathological findings include demyelination as well as axonal damage in both the central and peripheral nervous system. Diffusion tensor imaging (DTI) has emerged as a powerful noninvasive technique that is sensitive to these white matter disease processes. Increases in radial diffusivity (λ⟂) and decreases in axial diffusivity (λ∥) correlate with histopathological evidence of demyelination and axonal damage, respectively. Compared to age-matched, normal littermates, DTI of optic nerve and trigeminal nerve in end-stage Twitcher mice displayed a statistically significant increase in λ⟂ and decrease in λ∥, consistent with previously characterized demyelination and axonal damage in these regions. In the Twitcher spinal cord, a statistically significant decrease in λ∥ was identified in both the dorsal and ventrolateral white matter, relative to normal controls. These results were consistent with immunofluorescence evidence of axonal damage in these areas as detected by staining for nonphosphorylated neurofilaments (SMI32). Increase in λ⟂ in Twitcher spinal cord white matter relative to normal controls reached statistical significance in the dorsal columns and approached statistical significance in the ventrolateral region. Correlative reduced levels of myelin basic protein were detected by immunofluorescent staining in both these white matter regions in the Twitcher spinal cord. Fractional anisotropy, a nonspecific but sensitive indicator of white matter disease, was significantly reduced in the optic nerve, trigeminal nerve, and throughout the spinal cord white matter of Twitcher mice, relative to normal controls. This first reported application of spinal cord DTI in the setting of GLD holds potential as a noninvasive, quantitative assay of therapeutic efficacy in future treatment studies. Copyright © 2009 John Wiley & Sons, Ltd.

Research paper thumbnail of Retroviral Coexpression of Thymidylate Synthase and Dihydrofolate Reductase Confers Fluoropyrimidine and Antifolate Resistance

Biochemical and Biophysical Research Communications, 1998

myelosuppression has advanced to clinical trials (8-10). Retroviral gene transfer of dominant sel... more myelosuppression has advanced to clinical trials (8-10). Retroviral gene transfer of dominant selectable Second, drug resistance genes can function as domimarkers into hematopoietic cells can be used to select nant selectable markers and allow for the selection and genetically modified cells in vivo or to attenuate the expansion of genetically modified cells (1,6). In light of toxic effects of chemotherapeutic agents. We show that results from clinical trials which routinely show low retroviral gene transfer of thymidylate synthase (TS) level transduction of cells capable of hematopoietic reconfers resistance to TS directed anticancer agents constitution, in vivo or ex vivo selection and expansion and that co-expression of TS and dihydrofolate reducof genetically modified cells may be necessary for the tase (DHFR) confers resistance to TS and DHFR cytosuccessful application of gene therapy for hematopoitoxic agents. Retroviral vectors encoding Escherichia etic disorders (11-14).

Research paper thumbnail of VEGF disrupts the neonatal blood–brain barrier and increases life span after non-ablative BMT in a murine model of congenital neurodegeneration caused by a lysosomal enzyme deficiency

Experimental Neurology, 2004

The course of certain congenital neurodegenerative diseases like lysosomal storage diseases (LSDs... more The course of certain congenital neurodegenerative diseases like lysosomal storage diseases (LSDs) begins shortly after birth and can progress quickly. Ideally, therapeutic interventions for LSDs, which include bone marrow transplantation (BMT), recombinant enzyme replacement, or systemic viral-mediated gene therapy, should be initiated at birth. However, the blood -brain barrier (BBB) remains an obstacle to effective therapy even when these strategies are initiated at birth. We studied whether VEGF, an endothelial cell mitogen and permeability factor, can open the BBB in newborn mice for therapeutic purposes. Intravenous (IV) administration of VEGF at birth increased BBB permeability within 2 h. The increased permeability persisted for at least 24 h, became undetectable 48 h after injection, and was restricted to newborns. Systemic VEGF treatment before BMT or administration of recombinant lentivirus resulted in increased numbers of both donor cells and virus-transduced cells, respectively, in the recipient brain. Administration of VEGF before BMT in newborn mice with a neurodegenerative LSD, globoid-cell leukodystrophy, resulted in a significant increase in life span compared to affected animals that were injected with saline before BMT. D

Research paper thumbnail of Cirrhosis Originally Diagnosed as Nonalcoholic Steatohepatitis

Research paper thumbnail of AAV2/5 Vector Expressing Galactocerebrosidase Ameliorates CNS Disease in the Murine Model of Globoid-cell Leukodystrophy more Efficiently than AAV2

Molecular Therapy, 2005

Globoid-cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by ... more Globoid-cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by mutations in the galactosylceramidase (GALC) gene. Infantile GLD has a lethal course with severe cerebral demyelination that progresses to death by 2 years of age. In the current study twitcher mice, an authentic murine model of infantile GLD, were given intracranial injections of either recombinant adeno-associated virus serotype 2 encoding the murine Galc cDNA (AAV2-GALC) or the same genome pseudotyped with AAV5 capsid proteins (AAV2/5-GALC) on day 3 of age. The group injected intracranially with AAV2/5-GALC had approximately 25-fold greater than normal Galc levels in the brain, while AAV2-GALC-injected animals had 28% normal levels. The average life expectancy of twitcher mice (c38 days) was significantly ( P b 0.0001) increased to 48 and 52 days for the AAV2-GALC-and AAV2/5-GALC-treated groups, respectively. The AAV2/5-GALC group performed significantly better in a battery of behavioral tests compared to untreated, AAV2-GFPtreated, or AAV2-treated twitcher animals. This longitudinal study demonstrated that AAV2/5-GALC-mediated gene therapy resulted in higher levels of Galc expression and slowed the neurologic deterioration more completely than AAV2-GALC in the murine model of globoid-cell leukodystrophy. However, the clinical improvements, as assessed by behavioral tests and life span, were only modest.

Research paper thumbnail of The analytical specificity of human chorionic gonadotropin assays determined using WHO International Reference Reagents

Clinica Chimica Acta, 2010

Background: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with consi... more Background: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with considerable molecular heterogeneity. There is uncertainty regarding which hCG variants are detected by different hCG assays. The analytical specificity of 8 hCG assays was investigated. Methods: WHO International Reference Reagents for hCG, nicked hCG (hCGn), beta subunit (hCGβ), nicked beta subunit (hCGβn), and beta core fragment (hCGβcf) were individually added to hCG-free human serum. Specimens were analyzed with 8 commercially available hCG assays. Equimolar detection of hCG variants was defined as a recovery of 90-110%. Results: All assays detected hCG and hCGn with mean recoveries of 98.3 and 94.6%, respectively. Seven assays detected hCGβ (mean recovery 103.8%) but with high variation, and equimolar detection was observed only in four. The mean recovery of hCGβn was 85.5% but was highly variable with only two assays showing equimolar detection. With a mean recovery of 53.4%, two assays detected hCGβcf and both underestimated it considerably. Information provided by the assay manufacturer regarding hCG variant analytical specificity was inadequate or unclear in 75% of the assays. Conclusions: hCG assays vary considerably in their ability to detect different hCG variants. Manufacturers of hCG assays should clearly indicate the hCG variant specificity of their reagent systems.

Research paper thumbnail of Assessment of the Diagnostic Accuracy of the TDx-FLM II to Predict Fetal Lung Maturity

Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and r... more Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and rapid assessment of markers of fetal lung maturity is critical to clinicians in deciding whether to deliver a preterm infant. Our objective was to determine the optimal diagnostic cutoff value for the TDx-FLM II assay (Abbott Laboratories) for predicting clinically significant RDS. Methods: Amniotic fluid TDx-FLM II data were collected retrospectively over 4 years. Women were included in the study if they had delivered within 72 h of TDx-FLM II testing and both the mother and infant charts could be reviewed. Women who had been treated with steroids and delivered unaffected infants were excluded from the analysis. The diagnosis of RDS was defined as infants who either were treated with surfactant and/or were placed on a ventilator and/or required continuous positive airway pressure for >1 day. Results: A total of 185 women met all entry criteria (15 RDS, 170 non-RDS). A cutoff value for a mature result of >45 mg/g gave a sensitivity of 100% (95% confidence interval, 82-100%) and a specificity of 90% (95% confidence interval, 78 -89%). Conclusions: The TDx-FLM II appears to predict clinically significant RDS when a cutoff of >45 mg/g is used for mature results. Further studies will be required to confirm these findings.

Research paper thumbnail of Use of Serum FSH to Identify Perimenopausal Women with Pituitary hCG

Clinical Chemistry, 2008

BACKGROUND: Human chorionic gonadotropin (hCG) tests are performed on many female patients before... more BACKGROUND: Human chorionic gonadotropin (hCG) tests are performed on many female patients before performing medical procedures or administering medications that may harm a fetus. hCG of pituitary origin has been shown to increase with age. Therefore, mild increases in serum hCG in an older patient can be of pituitary origin and does not necessarily indicate pregnancy. The inability to rule out pregnancy in perimenopausal women can create clinical confusion and may delay needed therapies. Our objective was to determine the diagnostic utility of serum follicle-stimulating hormone (FSH) concentrations to rule out hCG of placental origin in perimenopausal women with a low concentration of serum hCG (5.0 -14.0 IU/L).

Research paper thumbnail of Patient Misidentifications Caused By Errors in Standard Barcode Technology

Clinical Chemistry, 2010

BACKGROUND: Bar code technology has decreased transcription errors in many healthcare application... more BACKGROUND: Bar code technology has decreased transcription errors in many healthcare applications. However, we have found that linear bar code identification methods are not failsafe. In this study, we sought to identify the sources of bar code decoding errors that generated incorrect patient identifiers when bar codes were scanned for point-of-care glucose testing and to develop solutions to prevent their occurrence.

Research paper thumbnail of Low Plasma Fibrinogen Levels with the Clauss Method during Anticoagulation with Bivalirudin

Research paper thumbnail of Assessment of the Diagnostic Accuracy of the TDx-FLM II to Predict Fetal Lung Maturity

Clinical Chemistry, 2002

Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and r... more Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and rapid assessment of markers of fetal lung maturity is critical to clinicians in deciding whether to deliver a preterm infant. Our objective was to determine the optimal diagnostic cutoff value for the TDx-FLM II assay (Abbott Laboratories) for predicting clinically significant RDS. Methods: Amniotic fluid TDx-FLM II data were collected retrospectively over 4 years. Women were included in the study if they had delivered within 72 h of TDx-FLM II testing and both the mother and infant charts could be reviewed. Women who had been treated with steroids and delivered unaffected infants were excluded from the analysis. The diagnosis of RDS was defined as infants who either were treated with surfactant and/or were placed on a ventilator and/or required continuous positive airway pressure for >1 day. Results: A total of 185 women met all entry criteria (15 RDS, 170 non-RDS). A cutoff value for...

Research paper thumbnail of Where Are the Preanalytical Stability Standards?

The Journal of Applied Laboratory Medicine, 2018

Research paper thumbnail of Cirrhosis Originally Diagnosed as Nonalcoholic Steatohepatitis

Research paper thumbnail of Effectiveness of barcoding for reducing patient specimen and laboratory testing identification errors: A Laboratory Medicine Best Practices systematic review and meta-analysis

Clinical Biochemistry, 2012

Research paper thumbnail of Falsely Increased hCG in Patients with High Leukocyte Counts

Research paper thumbnail of Falsely Decreased Human Chorionic Gonadotropin (hCG) Results Due to Increased Concentrations of the Free   Subunit and the   Core Fragment in Quantitative hCG Assays

Clinical Chemistry, 2010

BACKGROUND Earlier studies have shown that increased concentrations of certain human chorionic go... more BACKGROUND Earlier studies have shown that increased concentrations of certain human chorionic gonadotropin (hCG) variants can cause false-negative results in some qualitative hCG devices. The objective of this study was to determine if increased concentrations of hCGβ and hCGβ core fragment (hCGβcf) cause falsely decreased results on 9 commercially available quantitative hCG assays. METHODS Several concentrations of purified hCGβ and hCGβcf were added to 2 sets of 6 serum samples with and without a fixed concentration of intact hCG. We examined 9 widely used immunoassays to measure immunoreactive hCG. Falsely decreased results were defined as those in which the measured hCG concentration was ≤50% of expected. RESULTS High concentrations of hCGβ (≥240 000 pmol/L) produced falsely decreased hCG measurements in 2 assays known to detect this variant. Similarly, high concentrations of hCGβcf (≥63 000 pmol/L) produced falsely decreased hCG measurements in 3 assays that do not detect puri...

Research paper thumbnail of Strategies for Evaluating Critical Value Limits: Opportunities for Saving Time and Money Without Compromising Care

Research paper thumbnail of Strategies for Evaluating Critical Value Limits: Opportunities for Saving Time and Money Without Compromising Care

Research paper thumbnail of Teaching Laboratory Medicine to Medical Students: Implementation and Evaluation

Archives of Pathology & Laboratory Medicine, 2012

Laboratory medicine is an integral component of patient care. Approximately 60% to 70% of medical... more Laboratory medicine is an integral component of patient care. Approximately 60% to 70% of medical decisions are based on laboratory results. Physicians in specialties that order the tests are teaching medical students laboratory medicine and test use with minimal input from laboratory scientists who implement and maintain the quality control for those tests. To develop, implement, and evaluate a 1.5-day medical student clinical laboratory experience for fourth-year medical students in their last month of training. The experience was devised and directed by laboratory scientists and included a panel discussion, laboratory tours, case studies that focused on the goals and objectives recently published by the Academy of Clinical Laboratory Physicians and Scientists, and medical-student presentations highlighting salient points of the experience. The same knowledge quiz was administered at the beginning and end of the experience and 84 students took both quizzes. A score of 7 or more was obtained by 16 students (19%) on the initial quiz, whereas 34 (40%) obtained the same score on the final quiz; the improvement was found to be statistically significant (P = .002; t = 3.215), particularly in 3 out of the 10 questions administered. Although the assessment can only measure a small amount of knowledge recently acquired, the improvement observed by fourth-year medical students devoting a short period to learning laboratory medicine principles was encouraging. This medical student clinical laboratory experience format allowed teaching of a select group of laboratory medicine principles in 1.5 days to an entire medical school class.

Research paper thumbnail of Thyroid Function during Pregnancy

Background: This Case Conference reviews the normal changes in thyroid activity that occur during... more Background: This Case Conference reviews the normal changes in thyroid activity that occur during pregnancy and the proper use of laboratory tests for the diagnosis of thyroid dysfunction in the pregnant patient. Case: A woman in the 18th week of pregnancy presented with tachycardia, increased blood pressure, severe vomiting, increased total and free thyroid hormone concentrations, a thyroid-stimulating hormone (TSH) concentration within the reference interval, and an increased human chorionic gonadotropin (hCG) ␤-subunit concentration. Issues: During pregnancy, normal thyroid activity undergoes significant changes, including a two-to threefold increase in thyroxine-binding globulin concentrations, a 30 -100% increase in total triiodothyronine and thyroxine concentrations, increased serum thyroglobulin, and increased renal iodide clearance. Furthermore, hCG has mild thyroid stimulating activity. Pregnancy produces an overall increase in thyroid activity, which allows the healthy individual to remain in a net euthyroid state. However, both hyper-and hypothyroidism can occur in pregnant patients. In addition, two pregnancy-specific conditions, hyperemesis gravidarum and gestational trophoblastic disease, can lead to clinical hyperthyroidism. The normal changes in thyroid activity and the association of pregnancy with conditions that can cause hyperthyroidism necessitates careful interpretation of thyroid function tests during pregnancy. Conclusion: Assessment of thyroid function during pregnancy should be done with a careful clinical evaluation of the patient's symptoms as well as measurement of TSH and free, not total, thyroid hormones. Measurement of thyroid autoantibodies may also be useful in selected cases to detect maternal Graves disease or Hashi-moto thyroiditis and to assess risk of fetal or neonatal consequences of maternal thyroid dysfunction.

Research paper thumbnail of Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and cranial nerves of a murine model of globoid cell leukodystrophy

Nmr in Biomedicine, 2009

Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of ... more Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactosylceramidase. In both human patients and the authentic murine Twitcher model, pathological findings include demyelination as well as axonal damage in both the central and peripheral nervous system. Diffusion tensor imaging (DTI) has emerged as a powerful noninvasive technique that is sensitive to these white matter disease processes. Increases in radial diffusivity (λ⟂) and decreases in axial diffusivity (λ∥) correlate with histopathological evidence of demyelination and axonal damage, respectively. Compared to age-matched, normal littermates, DTI of optic nerve and trigeminal nerve in end-stage Twitcher mice displayed a statistically significant increase in λ⟂ and decrease in λ∥, consistent with previously characterized demyelination and axonal damage in these regions. In the Twitcher spinal cord, a statistically significant decrease in λ∥ was identified in both the dorsal and ventrolateral white matter, relative to normal controls. These results were consistent with immunofluorescence evidence of axonal damage in these areas as detected by staining for nonphosphorylated neurofilaments (SMI32). Increase in λ⟂ in Twitcher spinal cord white matter relative to normal controls reached statistical significance in the dorsal columns and approached statistical significance in the ventrolateral region. Correlative reduced levels of myelin basic protein were detected by immunofluorescent staining in both these white matter regions in the Twitcher spinal cord. Fractional anisotropy, a nonspecific but sensitive indicator of white matter disease, was significantly reduced in the optic nerve, trigeminal nerve, and throughout the spinal cord white matter of Twitcher mice, relative to normal controls. This first reported application of spinal cord DTI in the setting of GLD holds potential as a noninvasive, quantitative assay of therapeutic efficacy in future treatment studies. Copyright © 2009 John Wiley & Sons, Ltd.

Research paper thumbnail of Retroviral Coexpression of Thymidylate Synthase and Dihydrofolate Reductase Confers Fluoropyrimidine and Antifolate Resistance

Biochemical and Biophysical Research Communications, 1998

myelosuppression has advanced to clinical trials (8-10). Retroviral gene transfer of dominant sel... more myelosuppression has advanced to clinical trials (8-10). Retroviral gene transfer of dominant selectable Second, drug resistance genes can function as domimarkers into hematopoietic cells can be used to select nant selectable markers and allow for the selection and genetically modified cells in vivo or to attenuate the expansion of genetically modified cells (1,6). In light of toxic effects of chemotherapeutic agents. We show that results from clinical trials which routinely show low retroviral gene transfer of thymidylate synthase (TS) level transduction of cells capable of hematopoietic reconfers resistance to TS directed anticancer agents constitution, in vivo or ex vivo selection and expansion and that co-expression of TS and dihydrofolate reducof genetically modified cells may be necessary for the tase (DHFR) confers resistance to TS and DHFR cytosuccessful application of gene therapy for hematopoitoxic agents. Retroviral vectors encoding Escherichia etic disorders (11-14).

Research paper thumbnail of VEGF disrupts the neonatal blood–brain barrier and increases life span after non-ablative BMT in a murine model of congenital neurodegeneration caused by a lysosomal enzyme deficiency

Experimental Neurology, 2004

The course of certain congenital neurodegenerative diseases like lysosomal storage diseases (LSDs... more The course of certain congenital neurodegenerative diseases like lysosomal storage diseases (LSDs) begins shortly after birth and can progress quickly. Ideally, therapeutic interventions for LSDs, which include bone marrow transplantation (BMT), recombinant enzyme replacement, or systemic viral-mediated gene therapy, should be initiated at birth. However, the blood -brain barrier (BBB) remains an obstacle to effective therapy even when these strategies are initiated at birth. We studied whether VEGF, an endothelial cell mitogen and permeability factor, can open the BBB in newborn mice for therapeutic purposes. Intravenous (IV) administration of VEGF at birth increased BBB permeability within 2 h. The increased permeability persisted for at least 24 h, became undetectable 48 h after injection, and was restricted to newborns. Systemic VEGF treatment before BMT or administration of recombinant lentivirus resulted in increased numbers of both donor cells and virus-transduced cells, respectively, in the recipient brain. Administration of VEGF before BMT in newborn mice with a neurodegenerative LSD, globoid-cell leukodystrophy, resulted in a significant increase in life span compared to affected animals that were injected with saline before BMT. D

Research paper thumbnail of Cirrhosis Originally Diagnosed as Nonalcoholic Steatohepatitis

Research paper thumbnail of AAV2/5 Vector Expressing Galactocerebrosidase Ameliorates CNS Disease in the Murine Model of Globoid-cell Leukodystrophy more Efficiently than AAV2

Molecular Therapy, 2005

Globoid-cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by ... more Globoid-cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by mutations in the galactosylceramidase (GALC) gene. Infantile GLD has a lethal course with severe cerebral demyelination that progresses to death by 2 years of age. In the current study twitcher mice, an authentic murine model of infantile GLD, were given intracranial injections of either recombinant adeno-associated virus serotype 2 encoding the murine Galc cDNA (AAV2-GALC) or the same genome pseudotyped with AAV5 capsid proteins (AAV2/5-GALC) on day 3 of age. The group injected intracranially with AAV2/5-GALC had approximately 25-fold greater than normal Galc levels in the brain, while AAV2-GALC-injected animals had 28% normal levels. The average life expectancy of twitcher mice (c38 days) was significantly ( P b 0.0001) increased to 48 and 52 days for the AAV2-GALC-and AAV2/5-GALC-treated groups, respectively. The AAV2/5-GALC group performed significantly better in a battery of behavioral tests compared to untreated, AAV2-GFPtreated, or AAV2-treated twitcher animals. This longitudinal study demonstrated that AAV2/5-GALC-mediated gene therapy resulted in higher levels of Galc expression and slowed the neurologic deterioration more completely than AAV2-GALC in the murine model of globoid-cell leukodystrophy. However, the clinical improvements, as assessed by behavioral tests and life span, were only modest.

Research paper thumbnail of The analytical specificity of human chorionic gonadotropin assays determined using WHO International Reference Reagents

Clinica Chimica Acta, 2010

Background: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with consi... more Background: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with considerable molecular heterogeneity. There is uncertainty regarding which hCG variants are detected by different hCG assays. The analytical specificity of 8 hCG assays was investigated. Methods: WHO International Reference Reagents for hCG, nicked hCG (hCGn), beta subunit (hCGβ), nicked beta subunit (hCGβn), and beta core fragment (hCGβcf) were individually added to hCG-free human serum. Specimens were analyzed with 8 commercially available hCG assays. Equimolar detection of hCG variants was defined as a recovery of 90-110%. Results: All assays detected hCG and hCGn with mean recoveries of 98.3 and 94.6%, respectively. Seven assays detected hCGβ (mean recovery 103.8%) but with high variation, and equimolar detection was observed only in four. The mean recovery of hCGβn was 85.5% but was highly variable with only two assays showing equimolar detection. With a mean recovery of 53.4%, two assays detected hCGβcf and both underestimated it considerably. Information provided by the assay manufacturer regarding hCG variant analytical specificity was inadequate or unclear in 75% of the assays. Conclusions: hCG assays vary considerably in their ability to detect different hCG variants. Manufacturers of hCG assays should clearly indicate the hCG variant specificity of their reagent systems.

Research paper thumbnail of Assessment of the Diagnostic Accuracy of the TDx-FLM II to Predict Fetal Lung Maturity

Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and r... more Background: Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and rapid assessment of markers of fetal lung maturity is critical to clinicians in deciding whether to deliver a preterm infant. Our objective was to determine the optimal diagnostic cutoff value for the TDx-FLM II assay (Abbott Laboratories) for predicting clinically significant RDS. Methods: Amniotic fluid TDx-FLM II data were collected retrospectively over 4 years. Women were included in the study if they had delivered within 72 h of TDx-FLM II testing and both the mother and infant charts could be reviewed. Women who had been treated with steroids and delivered unaffected infants were excluded from the analysis. The diagnosis of RDS was defined as infants who either were treated with surfactant and/or were placed on a ventilator and/or required continuous positive airway pressure for >1 day. Results: A total of 185 women met all entry criteria (15 RDS, 170 non-RDS). A cutoff value for a mature result of >45 mg/g gave a sensitivity of 100% (95% confidence interval, 82-100%) and a specificity of 90% (95% confidence interval, 78 -89%). Conclusions: The TDx-FLM II appears to predict clinically significant RDS when a cutoff of >45 mg/g is used for mature results. Further studies will be required to confirm these findings.

Research paper thumbnail of Use of Serum FSH to Identify Perimenopausal Women with Pituitary hCG

Clinical Chemistry, 2008

BACKGROUND: Human chorionic gonadotropin (hCG) tests are performed on many female patients before... more BACKGROUND: Human chorionic gonadotropin (hCG) tests are performed on many female patients before performing medical procedures or administering medications that may harm a fetus. hCG of pituitary origin has been shown to increase with age. Therefore, mild increases in serum hCG in an older patient can be of pituitary origin and does not necessarily indicate pregnancy. The inability to rule out pregnancy in perimenopausal women can create clinical confusion and may delay needed therapies. Our objective was to determine the diagnostic utility of serum follicle-stimulating hormone (FSH) concentrations to rule out hCG of placental origin in perimenopausal women with a low concentration of serum hCG (5.0 -14.0 IU/L).

Research paper thumbnail of Patient Misidentifications Caused By Errors in Standard Barcode Technology

Clinical Chemistry, 2010

BACKGROUND: Bar code technology has decreased transcription errors in many healthcare application... more BACKGROUND: Bar code technology has decreased transcription errors in many healthcare applications. However, we have found that linear bar code identification methods are not failsafe. In this study, we sought to identify the sources of bar code decoding errors that generated incorrect patient identifiers when bar codes were scanned for point-of-care glucose testing and to develop solutions to prevent their occurrence.

Research paper thumbnail of Low Plasma Fibrinogen Levels with the Clauss Method during Anticoagulation with Bivalirudin