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1.
Patient Prefer Adherence ; 10: 2163-2169, 2016.
Article in English | MEDLINE | ID: mdl-27822017

ABSTRACT

BACKGROUND: This study assessed treatment satisfaction of cystic fibrosis (CF) patients in a routine clinical setting for tobramycin inhalation powder (TIP), the first dry powder-inhaled antibiotic for Pseudomonas aeruginosa infection. METHODS: CF patients aged 6 years or older treated with at least one cycle of TIP completed a web survey on experience with TIP, including the Treatment Satisfaction Questionnaire for Medication (TSQM). Regression analysis determined the factors associated with TSQM global satisfaction. RESULTS: Eighty patients (mean age ± standard deviation: 24.4±9.4 years; 57.5% female; mean forced expiratory volume in 1 second ± standard deviation: 67.1%±27.3% predicted) completed the survey. The majority expressed satisfaction with TIP's administration time (100%), time to clean (97.1%), portability (97.1%), and ease of use (94.3%). Effectiveness was significantly associated with TSQM global satisfaction (regression R-squared: 0.54). CONCLUSION: Patient preferences for TIP were based on administration time and ease of use. Global satisfaction was related to greater patient-perceived effectiveness.

2.
J Inherit Metab Dis ; 38(3): 489-93, 2015 May.
Article in English | MEDLINE | ID: mdl-25070466

ABSTRACT

INTRODUCTION: Ketone formation is a normal response when hypoglycemia occurs. Since the majority of children with recurrent hypoglycemia cannot be diagnosed with a known endocrine or metabolic disorder on a critical sample, ketotic hypoglycemia has been described as the most common cause of low blood glucose concentrations in children. Critical samples, however, will miss the ketotic forms of glycogen storage disease (GSD), which present with elevated ketones, hypoglycemia, and normal hormonal concentrations. RESULTS: A total of 164 children (96 boys, 68 girls) were enrolled in the study. Prediction of pathogenicity of DNA changes using computer modeling confirmed pathology in 20 individuals [four GSD 0, two GSD VI, 12 GSD IX alpha, one GSD IX beta, one GSD IX gamma] (12%). Boys were most likely to have changes in the PHKA2 gene, consistent with GSD IX alpha, an X-linked disorder. CONCLUSIONS: Mutations in genes involved in glycogen synthesis and degradation were commonly found in children with idiopathic ketotic hypoglycemia. GSD IX is likely an unappreciated cause of ketotic hypoglycemia in children, while GSD 0 and VI are relatively uncommon. GSD IX alpha should particularly be considered in boys with unexplained hypoglycemia.


Subject(s)
Glycogen Storage Disease/genetics , Hypoglycemia/genetics , Ketosis/genetics , Child , Child, Preschool , Female , Humans , Infant , Male , Mutation , Sex Factors
3.
J Biomed Biotechnol ; 2011: 646257, 2011.
Article in English | MEDLINE | ID: mdl-21318173

ABSTRACT

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.


Subject(s)
Disease Models, Animal , Dog Diseases/genetics , Dog Diseases/metabolism , Glycogen Storage Disease Type I/genetics , Glycogen Storage Disease Type I/metabolism , Liver Diseases/genetics , Liver Diseases/metabolism , Animals , Clinical Trials as Topic , Dogs , Glycogen Storage Disease Type I/diagnosis , Glycogen Storage Disease Type I/pathology , Glycogen Storage Disease Type I/veterinary , Humans , Liver Diseases/veterinary
4.
J Inherit Metab Dis ; 33 Suppl 3: S151-7, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20386986

ABSTRACT

Patients with type Ia glycogen storage disease (GSD) have been surviving well into adulthood since continuous glucose therapy was introduced in the 1970s, and there have been many documented successful pregnancies in women with this condition. Historically, few individuals with type Ib GSD, however, survived into adulthood prior to the introduction of granulocyte colony stimulating factor (G-CSF) in the late 1980s. There are no previously published reports of pregnancies in GSD type Ib. In this case report we describe the course and management of five successful pregnancies in three patients with GSD type Ib. Patient 1 experienced an increase in glucose requirement in all three of her pregnancies, starting from the second trimester onwards. There were no major complications related to neutropenia except for oral ulcers. The infants did well, except for respiratory distress in two of them at birth. Patient 2 used cornstarch to maintain euglycemia, but precise dosing was not part of her regimen, and, hence, an increase in metabolic demands was difficult to demonstrate. She developed a renal calculus and urinary tract infection during her pregnancy and had chronic iron deficiency anemia but no neutropenia. The neonate did well after delivery. Patient 3 had poor follow-up during pregnancy. Increasing glucose requirements, worsening lipid profile, neutropenia associated with multiple infections, and anemia were noted. The newborn infant did well after delivery. In addition to the case reports, the challenges of the usage of G-CSF, the treatment of enterocolitis, and comparisons with the management of GSD Ia are discussed.


Subject(s)
Glucose/administration & dosage , Glycogen Storage Disease Type I/therapy , Live Birth , Perinatal Care , Pregnancy Complications/therapy , Starch/administration & dosage , Adult , Biomarkers/blood , Blood Glucose/metabolism , Drug Administration Routes , Drug Administration Schedule , Female , Glycogen Storage Disease Type I/blood , Glycogen Storage Disease Type I/complications , Glycogen Storage Disease Type I/diagnosis , Glycogen Storage Disease Type I/genetics , Humans , Lipids/blood , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/diagnosis , Pregnancy Complications/genetics , Survivors , Time Factors , Treatment Outcome
5.
Hum Gene Ther ; 21(7): 903-10, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20163245

ABSTRACT

Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-alpha. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver.


Subject(s)
Dependovirus/genetics , Genetic Therapy , Genetic Vectors , Glycogen Storage Disease Type I/therapy , Animals , Disease Models, Animal , Dogs , Genetic Vectors/administration & dosage , Glycogen Storage Disease Type I/genetics , Humans
6.
J Pediatr ; 154(4): 588-91, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19101686

ABSTRACT

OBJECTIVE: To determine cardiovascular disease risk in a larger cohort of patients with glycogen storage disease (GSD) I through the use of noninvasive measures of arterial function and anatomy. STUDY DESIGN: Carotid intima media thickness (IMT), radial artery tonometry, and brachial artery reactivity were performed in 28 patients with GSD I (13F/15M, mean age 23 years) and 23 control subjects (19F/4M, mean age 23 years). RESULTS: The primary outcome measure, mean left distal IMT was greater in the GSD cohort (0.500+/-0.055 mm) than in the control group (0.457+/-0.039 mm) (P= .002, adjusted for age, sex, and body mass index). Mean augmentation index measured by radial artery tonometry was higher in the GSD cohort (16.4%+/-14.0%) than in the control group (2.4%+/-8.7%) (P< .001). No significant difference was observed between mean brachial artery reactivity in the GSD cohort (6.3%+/-4.9% change) versus control subjects (6.6%+/-5.1% change) (P= .46). CONCLUSIONS: GSD I is associated with arterial dysfunction evident by increased IMT and augmentation index. Patients with GSD I may be at increased risk for cardiovascular disease.


Subject(s)
Atherosclerosis/pathology , Endothelium, Vascular/pathology , Glycogen Storage Disease Type I/pathology , Adolescent , Adult , Atherosclerosis/epidemiology , Brachial Artery/pathology , Carotid Artery, Common/pathology , Case-Control Studies , Cohort Studies , Female , Florida/epidemiology , Glycogen Storage Disease Type I/epidemiology , Humans , Male , Manometry , Radial Artery/pathology , Risk , Tunica Intima/pathology
7.
Am J Clin Nutr ; 88(5): 1272-6, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18996862

ABSTRACT

BACKGROUND: Type I glycogen storage disease (GSD) is caused by a deficiency of glucose-6-phosphatase resulting in severe fasting hypoglycemia. OBJECTIVE: We compared the efficacy of a new modified starch with the currently used cornstarch therapy in patients with type Ia and Ib GSD. DESIGN: This was a randomized, 2-d, double-blinded, crossover pilot study comparing the commonly used uncooked cornstarch with the experimental starch in 12 subjects (6 GSDIa, 6 GSDIb) aged >or=13 y. At 2200, the subjects were given 100 g of digestible starch, and glucose and lactate were measured hourly until the subject's plasma glucose concentration reached 60 mg/dL or until the subject had fasted for 10 h. The order in which the products were tested was randomized in a blinded fashion. RESULTS: The matched-pair Gehan rank test for censored survival was used to compare the therapies. The experimental starch maintained blood glucose concentrations significantly longer than did the traditional therapy (P = 0.013) in the 2-sided analysis. Most of the benefit was found to be after glucose concentrations fell below 70 mg/dL. The currently used cornstarch resulted in higher peak glucose concentrations and a more rapid rate of fall than did the new starch. CONCLUSIONS: The experimental starch was superior to standard therapy in preventing hypoglycemia (

Subject(s)
Blood Glucose/metabolism , Fasting/blood , Glycogen Storage Disease Type I/diet therapy , Hypoglycemia/prevention & control , Starch/metabolism , Starch/pharmacology , Adolescent , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Glycogen Storage Disease Type I/blood , Glycogen Storage Disease Type I/metabolism , Humans , Male , Pilot Projects , Safety
8.
Inflamm Bowel Dis ; 12(12): 1101-6, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17119383

ABSTRACT

BACKGROUND: Anemia in patients with Crohn's disease (CD) is a common problem of multifactorial origin, including blood loss, malabsorption of iron, and anemia of inflammation. Anemia of inflammation is caused by the effects of inflammatory cytokines [predominantly interleukin-6 (IL-6)] on iron transport in enterocytes and macrophages. We sought to elucidate alterations in iron absorption in pediatric patients with active and inactive CD. METHODS: Nineteen subjects with CD (8 female, 11 male patients) were recruited between April 2003 and June 2004. After an overnight fast, serum iron and hemoglobin levels, serum markers of inflammation [IL-6, C-reactive protein (CRP), and erythrocyte sedimentation rate], and a urine sample for hepcidin assay were obtained at 8 am. Ferrous sulfate (1 mg/kg) was administered orally, followed by determination of serum iron concentrations hourly for 4 hours after the ingestion of iron. An area under the curve for iron absorption was calculated for each patient data set. RESULTS: There was a strong inverse correlation between the area under the curve and IL-6 (P = 0.002) and area under the curve and CRP levels (P = 0.04). Similarly, the difference between baseline and 2-hour serum iron level (Delta[Fe]2hr) correlated with IL-6 (P = 0.008) and CRP (P = 0.045). When cutoff values for IL-6 (>5 pg/mL) and CRP (>1.0 mg/dL) were used, urine hepcidin levels also positively correlated with IL-6 and CRP levels (P = 0.003 and 0.007, respectively). CONCLUSIONS: Subjects with active CD have impaired oral iron absorption and elevated IL-6 levels compared with subjects with inactive disease. These findings suggest that oral iron may be of limited benefit to these patients. Future study is needed to define the molecular basis for impaired iron absorption.


Subject(s)
Crohn Disease/metabolism , Crohn Disease/pathology , Intestinal Absorption/physiology , Iron/metabolism , Malabsorption Syndromes/pathology , Adolescent , Adult , Biomarkers/analysis , Child , Cytokines/blood , Demography , Female , Humans , Inflammation/metabolism , Iron/blood , Male
9.
Mol Genet Metab ; 87(4): 284-8, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16337419

ABSTRACT

The glycogen storage diseases comprise several inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. In contrast to the classic hepatic glycogen storage diseases that are characterized by fasting hypoglycemia and hepatomegaly, the liver is not enlarged in GSD0. Patients with GSD0 typically have fasting ketotic hypoglycemia without prominent muscle symptoms. Most children are cognitively and developmentally normal. Short stature and osteopenia are common features, but other long-term complications, common in other types of GSD, have not been reported in GSD0. Until recently, the definitive diagnosis of GSD0 depended on the demonstration of decreased hepatic glycogen on a liver biopsy. The need for an invasive procedure may be one reason that this condition has been infrequently diagnosed. Mutation analysis of the GYS2 gene (12p12.2) is a non-invasive method for making this diagnosis in patients suspected to have this disorder. This mini-review discusses the pathophysiology of this disorder, use of mutation analysis to diagnose GSD0, and the clinical characteristics of all reported cases of GSD0.


Subject(s)
Glycogen Storage Disease/diagnosis , Glycogen Synthase/deficiency , Hypoglycemia/diagnosis , Ketosis/diagnosis , Liver/enzymology , Child , Child, Preschool , Glycogen Storage Disease/genetics , Glycogen Storage Disease/therapy , Humans , Hypoglycemia/genetics , Hypoglycemia/therapy , Isoenzymes/deficiency , Ketosis/genetics , Ketosis/therapy
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