Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 176
Filter
1.
J Dent Res ; 100(13): 1468-1474, 2021 12.
Article in English | MEDLINE | ID: mdl-34138663

ABSTRACT

Past research suggests there are systematic associations between oral health and chronic illness among older adults. Although causality has not yet been credibly established, periodontitis has been found to be associated with higher risk of both heart disease and stroke. We advance this literature by estimating the direct association between dental care use and systemic health using multiple waves of the 1992 to 2016 Health and Retirement Study. Through the inclusion of individual fixed effects in our regression models, we account for unobservable time-invariant characteristics of individuals that might otherwise bias estimates of the association between dental care use and health. We find statistically significant negative associations between dental care use and the number of health conditions, self-reported overall health, the incidence of heart disease, and the incidence of stroke. In particular, the use of dental care within the past 2 y is associated with a 2.7% reduction in the likelihood of being diagnosed with a heart condition and a reduction in the likelihood of a stroke diagnosis of between 5.3% and 11.6%. We also find large positive correlations between edentulism and the measures of chronic illness. Associations from models estimated separately for men and women are qualitatively similar to one another. These findings provide additional motivation for the consideration of a Medicare dental benefit.


Subject(s)
Medicare , Periodontitis , Aged , Dental Care , Female , Humans , Incidence , Male , Oral Health , United States/epidemiology
2.
Water Environ Res ; 90(4): 329-342, 2018 Apr 01.
Article in English | MEDLINE | ID: mdl-30188275

ABSTRACT

Hydrothermal Liquefaction (HTL) and Catalytic Hydrothermal Gasification (CHG) proof-of-concept bench-scale tests were performed to assess the potential of hydrothermal treatment for handling municipal wastewater sludge. HTL tests were conducted at 300 to 350 °C and 20 MPa on three different feeds: primary sludge, secondary sludge, and digested solids. Corresponding CHG tests were conducted at 350 °C and 20 MPa on the HTL aqueous phase output using a ruthenium-based catalyst. Biocrude yields ranged from 25 to 37%. Biocrude composition and quality were comparable to biocrudes generated from algae feeds. Subsequent hydrotreating of biocrude resulted in a product with comparable physical and chemical properties to crude oil. CHG product gas methane yields on a carbon basis ranged from 47 to 64%. Siloxane concentrations in the CHG product gas were below engine limits. The HTL-CHG process resulted in a chemical oxygen demand (COD) reduction of > 99.9% and a reduction in residual solids for disposal of 94 to 99%.


Subject(s)
Biofuels/analysis , Waste Disposal, Fluid/methods , Wastewater/chemistry , Sewage/chemistry , Water/chemistry
3.
J Ovarian Res ; 9(1): 39, 2016 Jun 29.
Article in English | MEDLINE | ID: mdl-27357284

ABSTRACT

BACKGROUND: Prenatal testosterone (T) excess from days 30-90 of gestation disrupts gonadotropin surge and ovarian follicular dynamics and induces insulin resistance and functional hyperandrogenism in sheep. T treatment from days 60-90 of gestation produces a milder phenotype, albeit with reduced fecundity. Using this milder phenotype, the aim of this study was to understand the relative postnatal contributions of androgen and insulin in mediating the prenatal T induced disruptions in ovarian follicular dynamics. METHODS: Four experimental groups were generated: 1) control (vehicle treatment), 2) prenatal T-treated (100 mg i.m. administration of T propionate twice weekly from days 60-90 of gestation), 3) prenatal T plus postnatal anti-androgen treated (daily oral dose of 15 mg/kg/day of flutamide beginning at 8 weeks of age) and 4) prenatal T and postnatal insulin sensitizer-treated (daily oral dose of 8 mg/day rosiglitazone beginning at 8 weeks of age). Follicular response to a controlled ovarian stimulation protocol was tested during their third breeding season. Main outcome measures included the determination of number and size of ovarian follicles and intrafollicular concentrations of steroids. RESULTS: At the end of the controlled ovarian stimulation, the number of follicles approaching ovulatory size (≥6 mm) were ~35 % lower in prenatal T-treated (6.5 ± 1.8) compared to controls (9.8 ± 2.0). Postnatal anti-androgen (10.3 ± 1.9), but not insulin sensitizer (5.0 ± 0.9), treatment prevented this decrease. Preovulatory sized follicles in the T group had lower intrafollicular T, androstenedione, and progesterone compared to that of the control group. Intrafollicular steroid disruption was partially reversed solely by postnatal insulin sensitizer treatment. CONCLUSIONS: These results demonstrate that the final preovulatory follicular growth and intrafollicular steroid milieu is impaired in prenatal T-treated females. The findings are consistent with the lower fertility rate reported earlier in these females. The finding that final follicle growth was fully rescued by postnatal anti-androgen treatment and intrafollicular steroid milieu partially by insulin sensitizer treatment suggest that both androgenic and insulin pathway disruptions contribute to the compromised follicular phenotype of prenatal T-treated females.


Subject(s)
Ovarian Follicle/physiology , Steroids/biosynthesis , Testosterone/metabolism , Androgens/metabolism , Androgens/pharmacology , Animals , Estradiol/metabolism , Female , Ovarian Follicle/cytology , Ovarian Follicle/drug effects , Ovary/drug effects , Ovary/physiology , Pregnancy , Sheep , Testosterone/pharmacology
4.
Epilepsy Behav ; 42: 129-37, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25513768

ABSTRACT

OBJECTIVE: Cosmetic side effects (CSEs) such as weight gain and alopecia are common, undesirable effects associated with several AEDs. The objective of the study was to compare the CSE profiles in a large specialty practice-based sample of patients taking both older and newer AEDs. METHODS: As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 1903 adult patients (≥16years of age) newly started on an AED. Cosmetic side effects were determined by patient or physician report in the medical record and included acne, gingival hyperplasia, hair loss, hirsutism, and weight gain. We compared the overall rate of CSEs and intolerable CSEs (ICSEs-CSEs that led to dosage reduction or discontinuation) between different AEDs in both monotherapy and polytherapy. RESULTS: Overall, CSEs occurred in 110/1903 (5.8%) patients and led to intolerability in 70/1903 (3.7%) patients. Weight gain was the most commonly reported CSE (68/1903, 3.6%) and led to intolerability in 63 (3.3%) patients. Alopecia was the second most common patient-reported CSE (36/1903, 1.9%) and was intolerable in 33/1903 (1.7%) patients. Risk factors for CSEs included female sex (7.0% vs. 4.3% in males; p<0.05) and any prior CSE (37% vs. 2.9% in patients without prior CSE; p<0.001). Significantly more CSEs were attributed to valproic acid (59/270; 21.9%; p<0.001) and pregabalin (14/143; 9.8%; p<0.001) than to all other AEDs. Significantly less CSEs were attributed to levetiracetam (7/524; 1.3%; p=0.002). Weight gain was most frequently associated with valproic acid (35/270; 13.0%; p<0.001) and pregabalin (12/143; 8.4%; p<0.001). Hair loss was most commonly reported among patients taking valproic acid (24/270; 8.9%; p<0.001). Finally, gingival hyperplasia was most commonly reported in patients taking phenytoin (10/404; 2.5%; p<0.001). Cosmetic side effects leading to dosage change or discontinuation occurred most frequently with pregabalin and valproic acid compared with all other AEDs (13.3 and 5.6% vs. 2.3%; p<0.001). For patients who had been on an AED in monotherapy (n=677), CSEs and ICSEs were still more likely to be attributed to valproic acid (30.2% and 17.1%, respectively) than to any other AED (both p<0.001). SIGNIFICANCE: Weight gain and alopecia were the most common patient-reported CSEs in this study, and weight gain was the most likely cosmetic side effect to result in dosage adjustment or medication discontinuation. Particular attention should be paid to pregabalin, phenytoin, and valproic acid when considering cosmetic side effects. Female patients and patients who have had prior CSE(s) to AED(s) were more likely to report CSEs. Knowledge of specific CSE rates for each AED found in this study may be useful in clinical practice.


Subject(s)
Alopecia/chemically induced , Anticonvulsants/adverse effects , Epilepsy/drug therapy , Phenytoin/adverse effects , Valproic Acid/adverse effects , Weight Gain/drug effects , gamma-Aminobutyric Acid/analogs & derivatives , Acne Vulgaris/chemically induced , Adult , Female , Gingival Diseases/chemically induced , Hirsutism/chemically induced , Humans , Levetiracetam , Male , Middle Aged , Piracetam/adverse effects , Piracetam/analogs & derivatives , Pregabalin , Risk Factors , Sex Factors , gamma-Aminobutyric Acid/adverse effects
5.
Tissue Antigens ; 83(4): 273-85, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24641504

ABSTRACT

S5D-SRCRB is a novel mouse secretory glycoprotein belonging to the ancient and highly conserved scavenger receptor cysteine-rich superfamily of protein receptors. Available evidence indicates that S5D-SRCRB interacts with conserved microbial cell wall components, as well as with some endogenous proteins, and presents a restricted tissue expression pattern. This study further analyzes the expression of S5D-SRCRB along the mouse urogenital tract. Immunohistochemical staining for S5D-SRCRB was observed in spermatocytes from seminiferous tubules and in the epithelial surface from urethra and bladder, as well as in kidney tubules, mainly from medulla and papilla. Double stainings showed that S5D-SRCRB is expressed in both principal (P) and intercalated (IC) cells from renal collecting ducts (CD). By using an in vitro cell model of IC cell differentiation, preferential expression of S5D-SRCRB was observed in the apical border of terminally differentiated IC. Colocalization of S5D-SRCRB with galectin-3 (Gal-3) was also observed in kidney and bladder, but not in testis, supporting concurrent biochemical studies demonstrating the carbohydrate-dependent interaction of Gal-3 and S5D-SRCRB. Furthermore, upregulation of S5D-SRCRB expression was observed in in vitro and in vivo models of bacterial aggression, reinforcing the emerging view that CD, and specially IC, are important players in innate defense of the urinary tract against infection. Taken together, the results indicate that S5D-SRCRB is an integral component of the urogenital tract involved in innate immune functions.


Subject(s)
Gene Expression Regulation/immunology , Immunity, Innate , Scavenger Receptors, Class B/immunology , Urethra/immunology , Urinary Bladder/immunology , Animals , Mice , Mice, Inbred BALB C , Reproductive Tract Infections/immunology , Reproductive Tract Infections/metabolism , Scavenger Receptors, Class B/biosynthesis , Urethra/metabolism , Urinary Bladder/metabolism , Urinary Tract Infections/immunology , Urinary Tract Infections/metabolism
6.
Rev Sci Instrum ; 84(10): 105112, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24182168

ABSTRACT

As the production, distribution, and storage of renewable energy based fuels usually are performed under high pressures and as there is a lack of in situ high pressure gas analysis instruments on the market, the aim of this work was to develop a method for in situ high pressure gas analysis of biogas and hydrogen containing gas mixtures. The analysis is based on in situ measurements of optical, thermo physical, and electromagnetic properties in gas mixtures with newly developed high pressure sensors. This article depicts the calculation of compositions from the measured properties, which is carried out iteratively by using highly accurate equations of state for gas mixtures. The validation of the method consisted of the generation and measurement of several mixtures, of which three are presented herein: a first mixture of 64.9 mol. % methane, 17.1 mol. % carbon dioxide, 9 mol. % helium, and 9 mol. % ethane at 323 K and 423 K in a pressure range from 2.5 MPa to 17 MPa; a second mixture of 93.0 mol. % methane, 4.0 mol. % propane, 2.0 mol. % carbon dioxide, and 1.0 mol. % nitrogen at 303 K, 313 K, and 323 K in a pressure range from 1.2 MPa to 3 MPa; and a third mixture of 64.9 mol. % methane, 30.1 mol. % carbon dioxide, and 5.0 mol. % nitrogen at 303 K, 313 K, and 323 K in a pressure range from 2.5 MPa to 4 MPa. The analysis of the tested gas mixtures showed that with measured density, velocity of sound, and relative permittivity the composition can be determined with deviations below 1.9 mol. %, in most cases even below 1 mol. %. Comparing the calculated compositions with the generated gas mixture, the deviations were in the range of the combined uncertainty of measurement and property models.

7.
Endocrinology ; 154(5): 1731-42, 2013 May.
Article in English | MEDLINE | ID: mdl-23525243

ABSTRACT

Prenatal T excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested whether increases in visceral adiposity, adipocyte size, and total free fatty acids underlie the insulin resistance seen in prenatal T-treated female sheep. At approximately 16 months of age, insulin resistance and adipose tissue partitioning were determined via hyperinsulinemic euglycemic clamp and computed tomography, respectively, in control and prenatal T-treated females. Three months later, adipocyte size and free fatty acid composition were determined. Results revealed that at the postpubertal time points tested, insulin sensitivity was increased, visceral adiposity and adipocyte size in both the sc and the visceral compartments were reduced, and circulating palmitic acid was increased in prenatal T-treated females relative to controls. In parallel studies, 20-month-old prenatal T-treated females tended to have increased basal insulin to glucose ratio. Relative to earlier findings of reduced insulin sensitivity of prenatal T-treated females during early life and adulthood, these findings of increased insulin sensitivity and reduced adiposity postpubertally are suggestive of a period of developmental adaptation. The disruption observed in free fatty acid metabolism a few months later correspond to a time point when the insulin sensitivity indices of prenatal T-treated animals appear to shift toward insulin resistance. In summary, current findings of improved insulin sensitivity and reduced visceral adiposity in postpubertal prenatal T-treated sheep relative to our earlier findings of reduced insulin sensitivity during early postnatal life and adulthood are indicative of a period of developmental adaptation.


Subject(s)
Adiposity/drug effects , Embryonic Development/drug effects , Embryonic Development/physiology , Fatty Acids, Nonesterified/metabolism , Insulin Resistance , Prenatal Exposure Delayed Effects , Testosterone/pharmacology , Animals , Female , Insulin Resistance/physiology , Metabolome/drug effects , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Sex Factors , Sexual Maturation/drug effects , Sexual Maturation/physiology , Sheep/embryology , Sheep/growth & development , Sheep/metabolism , Sheep/physiology
8.
Rev Sci Instrum ; 80(3): 033505, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19334920

ABSTRACT

A video camera system is described as that measures the spatial distribution of visible line emission emitted from the main scrape-off layer (SOL) of plasmas in the DIII-D tokamak. A wide-angle lens installed on an equatorial port and an in-vessel mirror, which intercepts part of the lens' view, provide simultaneous tangential views of the SOL on the low-field and high-field sides of the plasma's equatorial plane. Tomographic reconstruction techniques are used to calculate the two-dimensional (2D) poloidal profiles from the raw data, and one-dimensional (1D) poloidal profiles simulating chordal views of other optical diagnostics from the 2D profiles. The 2D profiles can be compared with SOL plasma simulations; the 1D profiles with measurements from spectroscopic diagnostics. Sample results are presented, which elucidate carbon transport in plasmas with toroidally uniform injection of methane and argon transport in disruption mitigation experiments with massive gas jet injection.

9.
Circulation ; 118(3): 258-67, 2008 Jul 15.
Article in English | MEDLINE | ID: mdl-18574047

ABSTRACT

BACKGROUND: Platelets are the key to thrombus formation and play a role in the development of atherosclerosis. Noninvasive imaging of activated platelets would be of great clinical interest. Here, we evaluate the ability of a magnetic resonance imaging (MRI) contrast agent consisting of microparticles of iron oxide (MPIOs) and a single-chain antibody targeting ligand-induced binding sites (LIBS) on activated glycoprotein IIb/IIIa to image carotid artery thrombi and atherosclerotic plaques. METHODS AND RESULTS: Anti-LIBS antibody or control antibody was conjugated to 1-microm MPIOs (LIBS MPIO/control MPIO). Nonocclusive mural thrombi were induced in mice with 6% ferric chloride. MRI (at 9.4 T) was performed once before and repeatedly in 12-minute-long sequences after LIBS MPIO/control MPIO injection. After 36 minutes, a significant signal void, corresponding to MPIO accumulation, was observed with LIBS MPIOs but not control MPIOs (P<0.05). After thrombolysis, in LIBS MPIO-injected mice, the signal void subsided, indicating successful thrombolysis. On histology, the MPIO content of the thrombus, as well as thrombus size, correlated significantly with LIBS MPIO-induced signal void (both P<0.01). After ex vivo incubation of symptomatic human carotid plaques, MRI and histology confirmed binding to areas of platelet adhesion/aggregation for LIBS MPIOs but not for control MPIOs. CONCLUSIONS: LIBS MPIOs allow in vivo MRI of activated platelets with excellent contrast properties and monitoring of thrombolytic therapy. Furthermore, activated platelets were detected on the surface of symptomatic human carotid plaques by ex vivo MRI. This approach represents a novel noninvasive technique allowing the detection and quantification of platelet-containing thrombi.


Subject(s)
Drug Monitoring/methods , Ferric Compounds , Magnetic Resonance Imaging , Platelet Activation , Thrombolytic Therapy , Thrombosis/diagnosis , Animals , Atherosclerosis/diagnosis , Binding Sites , Carotid Artery Diseases/diagnosis , Contrast Media , Humans , In Vitro Techniques , Ligands , Male , Mice , Mice, Inbred C57BL , Particle Size , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Thrombosis/blood , Thrombosis/drug therapy
10.
Neurology ; 69(1): 32-41, 2007 Jul 03.
Article in English | MEDLINE | ID: mdl-17538034

ABSTRACT

OBJECTIVE: To characterize deficits in nonverbal recognition memory and functional brain changes associated with these deficits in Alzheimer disease (AD). METHODS: Using O-15 PET, we studied 11 patients with AD and 17 cognitively intact elders during the combined encoding and retrieval periods of a nonverbal recognition task. Both task conditions involved recognition of line drawings of abstract shapes. In both conditions, subjects were first presented a list of shapes as study items, and then a list as test items, containing items from the study list and foils. In the titrated demand condition, the shape study list size (SLS) was adjusted prior to imaging so that each subject performed at approximately 75% recognition accuracy; difficulty during PET scanning in this condition was approximately matched across subjects. A control task was used in which SLS = 1 shape. RESULTS: During performance of the titrated demand condition, SLS averaged 4.55 (+/-1.86) shapes for patients with AD and 7.53 (+/-4.81) for healthy elderly subjects (p = 0.031). However, both groups of subjects were closely matched on performance in the titrated demand condition during PET scanning with 72.17% (+/-7.98%) correct for patients with AD and 72.25% (+/-7.03%) for elders (p = 0.979). PET results demonstrated that patients with AD showed greater mean differences between the titrated demand condition and control in areas including the left fusiform and inferior frontal regions (Brodmann areas 19 and 45). CONCLUSIONS: Relative fusiform and inferior frontal differences may reflect the Alzheimer disease (AD) patients' compensatory engagement of alternate brain regions. The strategy used by patients with AD is likely to be a general mechanism of compensation, rather than task-specific.


Subject(s)
Alzheimer Disease/psychology , Brain Mapping , Frontal Lobe/physiopathology , Hippocampus/physiopathology , Memory Disorders/psychology , Pattern Recognition, Visual , Positron-Emission Tomography , Temporal Lobe/physiopathology , Adaptation, Physiological , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/drug therapy , Alzheimer Disease/physiopathology , Cerebrovascular Circulation , Cholinesterase Inhibitors/therapeutic use , Donepezil , Female , Frontal Lobe/diagnostic imaging , Hippocampus/diagnostic imaging , Humans , Indans/therapeutic use , Magnetic Resonance Imaging , Male , Memory Disorders/diagnostic imaging , Memory Disorders/drug therapy , Memory Disorders/etiology , Memory Disorders/physiopathology , Middle Aged , Neuropsychological Tests , Nootropic Agents/therapeutic use , Oxygen Radioisotopes , Pattern Recognition, Visual/physiology , Phenylcarbamates/therapeutic use , Piperidines/therapeutic use , Radiopharmaceuticals , Rivastigmine , Temporal Lobe/diagnostic imaging
11.
Exp Clin Endocrinol Diabetes ; 114(9): 527-32, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17115351

ABSTRACT

AIM: To compare the efficacy and safety of two analog insulins as starting regimens in insulin-naïve Type 2 diabetes patients. METHODS: In this randomized, open-label parallel study, twice-daily biphasic insulin aspart 30 (30% soluble and 70% protaminated insulin aspart; BIAsp 30) plus metformin (met) was compared with once-daily insulin glargine (glarg) plus glimepiride (glim) in 255 insulin-naïve patients (131 male; mean+/-SD age, 61.2+/-9.1 years). Mean baseline HbA (1c) (+/-SD) was 9.2+/-1.4% and 8.9+/-1.3% for BIAsp 30 plus met ( N=128) and glarg plus glim ( N=127), respectively ( P=0.0747). Primary endpoint was the difference in absolute change in HbA (1c) between groups after 26 weeks of treatment. RESULTS: HbA (1c) change was significantly greater in the BIAsp 30 plus met group than the glarg plus glim group (between-group difference: -0.5% (95% CI: -0.8; -0.2); P=0.0002). Mean prandial plasma glucose increment was significantly lower for BIAsp 30 plus met compared with glarg plus glim: 1.4+/-1.4 mmol/l vs. 2.2+/-1.8 mmol/l; P=0.0002. During the maintenance phase (weeks 6-26), one major hypoglycemic episode occurred in each group; 20.3% and 9% of patients experienced minor hypoglycemic episodes in the BIAsp 30 plus met and glarg plus glim groups, respectively ( P=0.0124). At end-of-trial, mean daily insulin doses were 0.40 U/kg BIAsp 30 and 0.39 U/kg glarg. Glarg plus glim-treated patients experienced significant weight gain of 1.5 kg (95% CI: 0.84; 2.19; P<0.0001). Weight change with BIAsp 30 plus met of +0.7 kg was not statistically significant (95% CI: -0.07; 1.42; P=0.0762). CONCLUSIONS: Starting insulin in Type 2 diabetes patients with twice-daily BIAsp 30 plus met can reduce HbA (1c) and mean prandial plasma glucose increment to a greater extent than once-daily glarg plus glim.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Insulin/analogs & derivatives , Metformin/administration & dosage , Sulfonylurea Compounds/administration & dosage , Aged , Biphasic Insulins , Blood Glucose/analysis , Body Weight/drug effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/epidemiology , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Insulin/administration & dosage , Insulin/adverse effects , Insulin Aspart , Insulin Glargine , Insulin, Isophane , Insulin, Long-Acting , Male , Metformin/adverse effects , Middle Aged , Sulfonylurea Compounds/adverse effects , Treatment Outcome
12.
Int J Clin Pharmacol Ther ; 42(1): 23-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14756383

ABSTRACT

AIM: The primary objective of this interaction study was to confirm preclinical data suggesting that moxifloxacin is not metabolized by CYP 450 isozymes. Itraconazole, a strong CYP 3A4 inhibitor, was used as comedication. METHODS: Twelve healthy male subjects were enrolled in this randomized study using 400 mg of oral moxifloxacin (MXF) administered alone and on the 7th day of a 9-day treatment regimen with itraconazole (ITR) 200 mg p.o., o.d. In addition to the assessment of safety and tolerability, non-compartmental pharmacokinetics of moxifloxacin, itraconazole and their respective metabolites were analyzed using plasma concentrations obtained using HPLC. RESULTS: All treatment regimens were safe and well-tolerated. No interaction with itraconazole was observed for moxifloxacin (relative bioavailability: 111.6% (90% CI 106.5 to 117.0%), C(max) ratio: 103.7% (84.8-126.9%) and its sulfometabolite (Ml) (AUC ratio: 107.7% (95.6, 121.4%), C(max) ratio: 105.8% (89.9-124.5%)). There was a 30% decrease in AUC with M2 moxifloxacin metabolite (glucuronide) accompanied by an approximately 54% increase in renal excretion, which may be due to changes in phase 2 metabolism and/or transport mechanisms altered by itraconazole. Exposure (AUC) to itraconazole and its hydroxymetabolite were marginally altered by moxifloxacin (AUC +5% for itraconazole and -5% for hydroxy-itraconazole (OH-ITR)) indicating the absence of a clinically relevant influence of moxifloxacin on itraconazole. Mean peak concentrations in plasma (C(max)) were reduced for ITR and OH-ITR by approximately 14% and 18%, respectively, when administered concomitantly with moxifloxacin. This was attributed to the sensitivity of itraconazole absorption to changes in gastric physiology (pH, gastric transit, administration after fasting) and was deemed as clinically irrelevant. CONCLUSION: Results of this study indicate that moxifloxacin is not a substrate for CYP 450 3A4 isozymes confirming previous preclinical in vitro data. Moxifloxacin can therefore be safely coadministered with CYP 3A4 inhibitors without the need for dose adjustment. No clinically relevant changes in the pharmacokinetics of itraconazole were observed during the study.


Subject(s)
Administration, Oral , Aza Compounds/pharmacokinetics , Drug Administration Schedule , Drug Therapy, Combination , Itraconazole/analogs & derivatives , Itraconazole/pharmacokinetics , Quinolines/pharmacokinetics , Adolescent , Adult , Aza Compounds/administration & dosage , Aza Compounds/metabolism , Biological Availability , Cross-Over Studies , Fasting , Fluoroquinolones , Germany , Humans , Itraconazole/administration & dosage , Itraconazole/metabolism , Male , Moxifloxacin , Quinolines/administration & dosage , Quinolines/metabolism
14.
Adv Space Res ; 32(1): 41-6, 2003.
Article in English | MEDLINE | ID: mdl-14727661

ABSTRACT

The risks to aircrew health posed by prolonged exposure to low levels of ionizing radiation at aircraft altitudes have recently received renewed attention. Civil and military aircraft currently on the drawing board are expected to operate at higher altitudes (>12 km) and fly longer ranges than do existing aircraft, thereby exposing their crews to higher levels of ionizing radiation, for longer periods of time. We are currently carrying out dosimetric measurements of the ionizing radiation environment at approximately 20 km altitude using portable Si detectors aboard NASA's two ER-2 high altitude research aircraft. The instruments, Liulin-4J, have been extensively calibrated at several particle accelerators. With these instruments, we can measure not only absorbed dose, but also variation of the absorbed dose as a function of time. We report radiation dose measurements as function of time, altitude, and latitude for several ER-2 missions.


Subject(s)
Aircraft/instrumentation , Altitude , Cosmic Radiation , Occupational Exposure , Radiation Monitoring/instrumentation , Humans , Models, Theoretical , Radiation Dosage , Radiometry , Silicon , United States , United States National Aeronautics and Space Administration
17.
Neurology ; 57(11): 2083-8, 2001 Dec 11.
Article in English | MEDLINE | ID: mdl-11739830

ABSTRACT

OBJECTIVE: To assess the effects of levodopa on resting-state brain metabolism in PD. BACKGROUND: In previous studies the authors used [18F] fluorodeoxyglucose (FDG) and PET to quantify regional metabolic abnormalities in PD. They found that this disease is characterized reproducibly by a specific abnormal PD-related pattern (PDRP). In this study the authors used IV levodopa infusion to quantify the effects of dopamine replacement on regional metabolism and PDRP network activity. They tested the hypothesis that clinical response to dopaminergic therapy correlates with these metabolic changes. METHODS: The authors used FDG/PET to measure resting-state regional brain metabolism in seven patients with PD (age, 59.4 +/- 4.2 years; Hoehn and Yahr stage, 1.9 +/- 0.7, mean +/- SD); subjects were scanned both off levodopa and during an individually titrated constant-rate IV levodopa infusion. The authors used statistical parametric mapping to identify significant changes in regional brain metabolism that occurred with this intervention. They also quantified levodopa-induced changes in PDRP expression. Metabolic changes with levodopa correlated with clinical improvement as measured by changes in Unified PD Rating Scale (UPDRS) motor scores. RESULTS: Levodopa infusion improved UPDRS motor ratings (30.6% +/- 12.0%, p < 0.002) and significantly decreased regional glucose metabolism in the left putamen, right thalamus, bilateral cerebellum, and left primary motor cortex (p < 0.001). Changes in pallidal metabolism correlated significantly with clinical improvement in UPDRS motor ratings (p < 0.01). Levodopa infusion also resulted in a significant (p = 0.01) decline in PDRP expression. The changes in PDRP activity mediated by levodopa correlated significantly with clinical improvement in UPDRS motor ratings (r = -0.78, p < 0.04). CONCLUSION: Levodopa reduces brain metabolism in the putamen, thalamus, and cerebellum in patients with PD. Additionally, levodopa reduces PD-related pattern activity, and the degree of network suppression correlates with clinical improvement. The response to dopaminergic therapy in Patients with PD may be determined by the modulation of cortico-striato-pallido-thalamocortical pathways.


Subject(s)
Energy Metabolism/drug effects , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Tomography, Emission-Computed , Aged , Blood Glucose/metabolism , Brain/diagnostic imaging , Brain/drug effects , Brain Mapping , Female , Fluorodeoxyglucose F18 , Humans , Levodopa/adverse effects , Male , Middle Aged , Neurologic Examination/drug effects , Parkinson Disease/diagnostic imaging , Reference Values
18.
J Nucl Med ; 42(11): 1591-5, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11696626

ABSTRACT

UNLABELLED: The identification of discrete patterns of altered functional brain circuitry in preclinical Huntington's disease (HD) gene carriers is important to understanding the pathophysiology of this disorder and could be useful as a biologic disease marker. The purpose of this study was to use PET imaging of regional cerebral glucose metabolism to identify abnormal networks of brain regions that are specifically related to the preclinical phase of HD. METHODS: Eighteen presymptomatic HD gene carriers, 13 early-stage HD patients, and 8 age-matched gene-negative relatives were scanned using PET with [(18)F]FDG to quantify regional glucose utilization. A network modeling strategy was applied to the FDG PET data to identify disease-related regional metabolic covariance patterns in the preclinical HD cohort. The outcome measures were the region weights defining the metabolic topography of the HD gene carriers and the subject scores quantifying the expression of the pattern in individual subjects. RESULTS: Network analysis of the presymptomatic carriers and the gene-negative control subjects revealed a significant metabolic covariance pattern characterized by caudate and putamenal hypometabolism but also included mediotemporal metabolic reductions as well as relative metabolic increases in the occipital cortex. Subject scores for this pattern were abnormally elevated in the preclinical group compared with those of the control group (P < 0.005) and in the early symptomatic group compared with those of the presymptomatic group (P < 0.005). CONCLUSION: These findings show that FDG PET with network analysis can be used to identify specific patterns of abnormal brain function in preclinical HD. The presence of discrete patterns of metabolic abnormality in preclinical HD carriers may provide a useful means of quantifying the rate of disease progression during the earliest phases of this illness.


Subject(s)
Fluorodeoxyglucose F18 , Huntington Disease/diagnostic imaging , Huntington Disease/metabolism , Radiopharmaceuticals , Adult , Brain/diagnostic imaging , Brain Chemistry/genetics , Brain Mapping , Female , Glucose/metabolism , Heterozygote , Humans , Huntington Disease/genetics , Male , Tomography, Emission-Computed
19.
Ann Neurol ; 50(4): 514-20, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11601502

ABSTRACT

We studied 6 advanced-stage Parkinson's disease patients with [18F] fluorodeoxyglucose/positron emission tomography before and 3 months after unilateral ablation of the subthalamic nucleus performed with microelectrode mapping. Operative changes in glucose metabolism were assessed by comparing baseline and postoperative scans. We also quantified operative changes in the activity of an abnormal Parkinson's disease-related metabolic network that we had identified in previous [18F] fluorodeoxyglucose/positron emission tomography studies. Following unilateral subthalamic nucleus ablation, a highly significant reduction in glucose utilization was present in the midbrain ipsilateral to the lesion site, most pronounced in the vicinity of the substantia nigra pars reticularis. Significant metabolic reductions were also present in the ipsilateral internal globus pallidus, ventral thalamus, and pons. Operative changes in Parkinson's disease network activity differed significantly for the lesioned and unlesioned hemispheres. In the lesioned hemisphere, network activity declined significantly following surgery, but was unaltered in the contralateral, unlesioned hemisphere. These results suggest that subthalamotomy reduces basal ganglia output through internal globus pallidus/substantia nigra pars reticularis and also influences downstream neural activity in the pons and ventral thalamus. This procedure also reduces the activity of abnormal Parkinson's disease-related metabolic brain networks, suggesting a widespread modulation of motor circuitry.


Subject(s)
Glucose/metabolism , Parkinson Disease/metabolism , Parkinson Disease/surgery , Subthalamic Nucleus/surgery , Adult , Cerebellar Nuclei/metabolism , Female , Fluorodeoxyglucose F18 , Globus Pallidus/metabolism , Humans , Male , Middle Aged , Parkinson Disease/diagnostic imaging , Pons/metabolism , Radiopharmaceuticals , Thalamus/metabolism , Tomography, Emission-Computed , Treatment Outcome
20.
J Am Dent Assoc ; 132(8): 1137-45, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11575023

ABSTRACT

BACKGROUND: Health insurance coverage has been shown to relate positively with the use of dental services. The purpose of the authors' study was to describe the level of dental coverage among U.S. children and to assess the impact of dental coverage on children's use of dental services and expenditures for dental care. METHODS: The focus of these analyses is on dental care coverage, use and expenditures for U.S. children during 1996. National estimates are provided for the population with dental coverage, the population with a dental visit, and mean total expenditure for each of several socioeconomic and demographic categories during 1996 using data from the Medical Expenditure Panel Survey. RESULTS: Fifty-two percent of children younger than 18 years of age had private dental coverage during 1996. Approximately 56 percent of children in families with a poverty status level of 133 percent of the federal poverty level or below were covered by Medicaid during 1996. Fifty-six percent of children with private coverage had made at least one dental visit, compared with 28 percent of noncovered children. Twenty-eight percent of children covered by Medicaid had made at least one dental visit compared with 19 percent of noncovered children. CONCLUSION: Medicaid dental coverage seems to have had a lesser effect on the likelihood of a child's having a dental visit than had private coverage. Improving oral health for poorer children may depend partly on improving the design of Medicaid dental coverage programs. PRACTICE IMPLICATIONS: By understanding these analyses, practitioners, advocates and policymakers will be better positioned to provide care, improve access and better meet the needs of all American children.


Subject(s)
Dental Care for Children/statistics & numerical data , Health Expenditures , Insurance Coverage , Insurance, Health , Adolescent , Child , Child, Preschool , Dental Care for Children/economics , Educational Status , Female , Health Services Accessibility , Health Status , Humans , Income , Infant , Infant, Newborn , Insurance, Dental/economics , Insurance, Health/economics , Male , Medicaid/economics , Oral Health , Poverty , Rural Population , Social Class , United States , Urban Population
SELECTION OF CITATIONS
SEARCH DETAIL
...