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1.
Physiol Res ; 70(3): 393-399, 2021 07 12.
Article in English | MEDLINE | ID: mdl-33982584

ABSTRACT

Decline in cardiac high-energy phosphate metabolism [phosphocreatine-to-ATP (PCr/ATP) ratio] and whole body metabolism increase the risk of heart failure and metabolic diseases. The aim of the present study was to assess the relationship between PCr/ATP ratio and measures of body metabolic function. A total of 35 healthy women (56+/-14.0 years of age) underwent cardiac 31P magnetic resonance spectroscopy to assess PCr/ATP ratio - an index of cardiac high-energy phosphate metabolism. Fasting and 2-hour glucose levels were assessed using oral glucose tolerance test. Indirect calorimetry was performed to determine oxygen consumption and resting metabolic rate. There were no significant relationships between PCr/ATP ratio and resting metabolic rate (r=-0.09, p=0.62), oxygen consumption (r=-0.11, p=0.54), fasting glucose levels (r=-0.31, p=0.07), and 2-hour plasma glucose (r=-0.10, p=0.58). Adjusted analysis for covariates including age, body mass index, fat mass, and physical activity, had no significant influence on the relationship between PCr/ATP ratio and body metabolism. In conclusion, the lack of relationship between cardiac PCr/ATP ratio, glucose control and metabolic rate may suggest that overall metabolic function does not influence cardiac high-energy phosphate metabolism.


Subject(s)
Adenosine Triphosphate/metabolism , Metabolism/physiology , Myocardium/metabolism , Phosphocreatine/metabolism , Adiposity , Adult , Aged , Aging , Blood Glucose/analysis , Body Mass Index , Exercise , Female , Humans , Middle Aged , Oxygen Consumption
2.
PLoS One ; 16(3): e0248204, 2021.
Article in English | MEDLINE | ID: mdl-33720946

ABSTRACT

Copper (Cu), iron (Fe), and zinc (Zn) are essential trace minerals for the reproduction, growth, and immunity of mammalian herbivore populations. We examined the relationships between Cu, Fe, and Zn in soils, common plants, and hepatic stores of two wild herbivores to assess the effects of weather, sex, and population density on the transfer of trace minerals from soils to mammals during the growing season. Soils, grasses, woody browse, hispid cotton rats (Sigmodon hispidus), and white-tailed deer (Odocoileus virginianus) were sampled across 19 sites. Concentrations of Cu, Fe, and Zn in grasses and browse species were not correlated with concentrations of those minerals in soils sampled from the same areas. Leaves of woody browse were higher in Cu, lower in Fe, and similar in Zn when compared with grasses. Available concentrations of soils were positively related to liver Cu and Zn in hispid cotton rats, which was consistent with the short lives and high productivity of these small mammals that rely on grass seed heads. Interactions between soil concentrations and weather also affected liver Cu and Fe in deer, which reflected the greater complexity of trophic transfers in large, long-lived, browsing herbivores. Population density was correlated with liver concentrations of Cu, Fe, and Zn in hispid cotton rats, and concentrations of Cu and Fe in deer. Liver Cu was < 5 mg/kg wet weight in at least 5% of animals at two of eight sites for hispid cotton rats and < 3.8 mg/kg wet weight in at least 5% of animals at three of 12 sites for deer, which could indicate regional limitation of Cu for populations of mammalian herbivores. Our data indicate that supplies of trace minerals may contribute to density dependence of herbivore populations. Local population density may therefore influence the prevalence of deficiency states and disease outbreak that exacerbate population cycles in wild mammals.


Subject(s)
Copper/metabolism , Deer/physiology , Iron/metabolism , Sigmodontinae/physiology , Zinc/metabolism , Animals , Copper/analysis , Female , Herbivory , Iron/analysis , Liver/chemistry , Liver/metabolism , Male , Seasons , Soil/chemistry , Trace Elements/analysis , Trace Elements/metabolism , Zinc/analysis
3.
BMC Pediatr ; 19(1): 131, 2019 04 25.
Article in English | MEDLINE | ID: mdl-31023296

ABSTRACT

BACKGROUND: Adolescents with DMD treated with chronic high dose GC therapy typically have profound pubertal delay. Testosterone, the main circulating androgen in men, promotes virilisation and growth with associated accrual of fat-free muscle mass and bone mineral content. Testosterone therapy is routinely used to mimic the normal stages of pubertal development in patients with hypogonadotrophic hypogonadism, androgen deficiency secondary to testicular disease and in constitutional delay of growth and puberty (CDGP). Improved life expectancy in DMD has meant that more adolescents are eligible for testosterone supplementation but there is little objective data regarding the impact of this treatment on muscle structure and function, bone integrity and overall well-being. METHODS: This is a single centre observational clinical trial (NCT02571205) that aims to follow the progress of 15 adolescents with Duchenne muscular dystrophy and delayed puberty as they are managed with incremental testosterone therapy to induce puberty. Subjects will all be treated with a steadily increasing dose of testosterone administered by injection every 4 weeks and data will be collected to help us determine the effectiveness and tolerability of the described treatment regimen. We will use the data to explore the effects of testosterone on pubertal development, growth, muscle strength and function, bone mineral density, body composition with a detailed record of any adverse events. We will also carry out interviews to explore the boys' views on the tolerability of the regimen. The study will last for 27 months in total for each participant. DISCUSSION: Our experience has indicated that testosterone treatment in adolescents with DMD is liked and well tolerated but we have not collected objective data on a specific treatment regimen and there is no current consensus. Testosterone supplementation is not part of the standard of care of pubertal delay in DMD but inclusion in future protocols may be appropriate depending on the results of this trial. TRIAL REGISTRATION: EudraCT Number: 2015-003195-68. Research Registry & References: Clinical trials.gov- NCT02571205 (registered 8/10/15).


Subject(s)
Glucocorticoids/adverse effects , Muscle Strength/drug effects , Muscular Dystrophy, Duchenne/drug therapy , Puberty, Delayed/drug therapy , Testosterone/administration & dosage , Adolescent , Body Composition/drug effects , Bone Density/drug effects , Child , Dose-Response Relationship, Drug , Drug Administration Schedule , Follow-Up Studies , Glucocorticoids/administration & dosage , Humans , Injections, Intramuscular , Male , Muscular Dystrophy, Duchenne/complications , Muscular Dystrophy, Duchenne/diagnosis , Patient Satisfaction , Prospective Studies , Treatment Outcome , United Kingdom
4.
Exp Gerontol ; 113: 80-85, 2018 11.
Article in English | MEDLINE | ID: mdl-30266472

ABSTRACT

INTRODUCTION: The loss of mitochondrial function and content have been implicated in sarcopenia although they have been little studied in the very old, the group in which sarcopenia is most common. In this pilot study, our aim was to determine if mitochondrial respiratory chain function and content are preserved among healthy 85-year-olds. METHODS: We recruited 19 participants (11 female) through their general practitioner and assessed their medical history, functional status and self-reported physical activity. We identified sarcopenia using grip strength, Timed Up-and-Go and bioimpedance analysis. We assessed mitochondrial respiratory chain function using phosphorous magnetic resonance spectroscopy, estimating τ1/2 PCr, the recovery half-time of phosphocreatine in the calf muscles following a bout of aerobic exercise. We performed a biopsy of the vastus lateralis muscle and assessed mitochondrial respiratory chain content by measuring levels of subunits of complex I and IV of the respiratory chain, expressed as Z-scores relative to that in young controls. RESULTS: Participants had a median (IQR) of 2 (1,3) long-term conditions, reported regular aerobic physical activity, and one participant (5.3%) had sarcopenia. Sixteen participants completed the magnetic resonance protocol and the mean (SD) τ1/2 PCr of 35.6 (11.3) seconds was in keeping with preserved mitochondrial function. Seven participants underwent muscle biopsy and the mean fibre Z-scores were -0.7 (0.7) and -0.2 (0.4) for complexes I and IV, respectively, suggesting preserved content of mitochondrial respiratory chain enzymes. CONCLUSION: Muscle mitochondrial respiratory chain function and content are preserved in a sample of active, well-functioning 85-year-olds, among whom sarcopenia was uncommon. The results from this study will help inform future work examining the association between muscle mitochondrial deficiency and sarcopenia.


Subject(s)
Electron Transport Complex I/metabolism , Mitochondria/metabolism , Muscle, Skeletal/physiology , Sarcopenia/physiopathology , Aged, 80 and over , Exercise , Female , Hand Strength , Humans , Magnetic Resonance Spectroscopy , Male , Muscle, Skeletal/pathology , Pilot Projects
5.
Diabet Med ; 33(12): 1723-1731, 2016 12.
Article in English | MEDLINE | ID: mdl-27589584

ABSTRACT

AIMS: To compare directly the impact of glucagon-like peptide-1 secretion on glucose metabolism in individuals with Type 2 diabetes listed for Roux-en-Y gastric bypass surgery, randomized to be studied before and 7 days after undergoing Roux-en-Y gastric bypass or after following a very-low-calorie diet. METHODS: A semi-solid meal test was used to investigate glucose, insulin and glucagon-like peptide-1 response. Insulin secretion in response to intravenous glucose and arginine stimulus was measured. Hepatic and pancreatic fat content was quantified using magnetic resonance imaging. RESULTS: The decrease in fat mass was almost identical in the Roux-en-Y gastric bypass and the very-low-calorie diet groups (3.0±0.3 and 3.0±0.7kg). The early rise in plasma glucose level and in acute insulin secretion were greater after Roux-en-Y gastric bypass than after a very-low-calorie diet; however, the early rise in glucagon-like peptide-1 was disproportionately greater (sevenfold) after Roux-en-Y gastric bypass than after a very-low-calorie diet. This did not translate into a greater improvement in fasting glucose level or area under the curve for glucose. The reduction in liver fat was greater after Roux-en-Y gastric bypass (29.8±3.7 vs 18.6±4.0%) and the relationships between weight loss and reduction in liver fat differed between the Roux-en-Y gastric bypass group and the very-low-calorie diet group. CONCLUSIONS: This study shows that gastroenterostomy increases the rate of nutrient absorption, bringing about a commensurately rapid rise in insulin level; however, there was no association with the large post-meal rise in glucagon-like peptide-1, and post-meal glucose homeostasis was similar in the Roux-en-Y gastric bypass and very-low-calorie diet groups. (Clinical trials registry number: ISRCTN11969319.).


Subject(s)
Caloric Restriction , Diabetes Mellitus, Type 2/therapy , Gastric Bypass , Glucagon-Like Peptide 1/metabolism , Adipose Tissue/metabolism , Adult , Aged , Amino Acids , Arginine/administration & dosage , Arginine/pharmacology , Blood Glucose/biosynthesis , Blood Glucose/metabolism , Body Composition , Chromium , Diabetes Mellitus, Type 2/metabolism , Female , Glucose/administration & dosage , Glucose/pharmacology , Glycated Hemoglobin/metabolism , Humans , Insulin/metabolism , Insulin Resistance/physiology , Insulin Secretion , Lipase/genetics , Liver/chemistry , Male , Membrane Proteins/genetics , Middle Aged , Nicotinic Acids , Pancreas/chemistry , Triglycerides/metabolism
7.
J Clin Pharm Ther ; 40(3): 299-303, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25893427

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: The Food and Drug Administration (FDA) instituted a risk evaluation mitigation strategy (REMS) for erythropoiesis-stimulating agent (ESA) use in patients with cancer in February 2010. Implementation of REMS was considered likely to reduce ESA use and increase red blood cell transfusions. We aimed to quantify ESA and transfusion use pre- and post-REMS. METHODS: A retrospective data analysis was conducted using the Medicare 5% Sample Database from 2008 through 2011. Patients were 66 years of age or older and had lung and/or breast cancers along with chemotherapy-induced anaemia. Patients initiated chemotherapy in pre-REMS and post-REMS periods (1Q2008 through 4Q2009 and 1Q2010 through 4Q2011, respectively). Logistic regression was used to evaluate differences in proportions of patients receiving ESAs and transfusions pre-REMS and post-REMS. RESULTS AND DISCUSSION: The pre-REMS group included 1526 patients and the post-REMS group included 1689 patients. ESA use in patients with lung cancer decreased 30·2% from pre- to post-REMS and 33·1% in patients with breast cancer. Both decreases were statistically significant. Transfusion rates increased 22·1% from the pre-REMS period to the pre-REMS period in patients with breast cancer (P < 0·0001), but there was no statistically significant change over time in patients with lung cancer. WHAT IS NEW AND CONCLUSION: Erythropoiesis-stimulating agent use decreased in patients with both lung and breast cancer (P < 0·0001), and transfusion rates increased significantly post-REMS in patients with breast cancer (P < 0·0001) but not in those with lung cancer.


Subject(s)
Anemia/drug therapy , Antineoplastic Agents/adverse effects , Erythrocyte Transfusion/statistics & numerical data , Hematinics/administration & dosage , Aged , Aged, 80 and over , Anemia/chemically induced , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Female , Hematinics/adverse effects , Humans , Logistic Models , Lung Neoplasms/drug therapy , Male , Retrospective Studies , Risk Assessment/methods , Risk Management/methods , United States , United States Food and Drug Administration
8.
Langmuir ; 30(6): 1566-72, 2014 Feb 18.
Article in English | MEDLINE | ID: mdl-24471906

ABSTRACT

Accurate interfacial tension data for fluid systems such as hydrocarbons and water is essential to many applications such as reservoir oil and gas recovery predictions. Conventional interfacial tension measurement techniques typically use optical images to analyze droplet shapes but require that the continuous-phase fluid be optically transparent and that the fluids are not refractive index matched. Magnetic resonance images obtain contrast between fluids using other mechanisms such as magnetic relaxation weighting, so systems that are impossible to measure with optical methods may be analyzed. In this article, we present high-field (9.4 T) MRI images of various droplets analyzed with axisymmetric drop shape analysis. The resultant interfacial tension data show good agreement with literature data. The method is subsequently demonstrated using both opaque continuous phases and refractive-index-matched fluids. We conclude with a brief consideration of the potential to extrapolate the methodology to lower magnetic fields (0.3 T), featuring more accessible hardware; although droplet imaging is possible, resolution and stability do not currently permit accurate interfacial tension measurements.


Subject(s)
Magnetic Resonance Imaging/methods , Surface Tension , Alkanes/chemistry , Glycerol/chemistry , Heptanes/chemistry , Hexanes/chemistry , Octanols/chemistry , Refractometry , Water/chemistry
9.
J Intern Med ; 271(3): 264-70, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21793948

ABSTRACT

OBJECTIVES: Impaired cardiac function has been confirmed in patients with chronic fatigue syndrome (CFS). Magnetic resonance cardiac tagging is a novel technique that assesses myocardial wall function in vivo. We hypothesized that patients with CFS may have impaired development and release of myocardial torsion and strain. METHODS: Cardiac morphology and function were assessed using magnetic resonance imaging and cardiac tagging methodology in 12 CFS patients (Fukuda) and 10 matched controls. RESULTS: Compared to controls, the CFS group had substantially reduced left ventricular mass (reduced by 23%), end-diastolic volume (30%), stroke volume (29%) and cardiac output (25%). Residual torsion at 150% of the end-systolic time was found to be significantly higher in the patients with CFS (5.3 ± 1.6°) compared to the control group (1.7 ± 0.7°, P = 0.0001). End-diastolic volume index correlated negatively with both torsion-to-endocardial-strain ratio (TSR) (r = -0.65, P = 0.02) and the residual torsion at 150% end-systolic time (r = -0.76, P = 0.004), so decreased end-diastolic volume is associated with raised TSR and torsion persisting longer into diastole. Reduced end-diastolic volume index also correlated significantly with increased radial thickening (r = -0.65, P = 0.03) and impaired diastolic function represented by the ratio of early to late ventricular filling velocity (E/A ratio, r = 0.71, P = 0.009) and early filling percentage (r = 0.73, P = 0.008). CONCLUSION: Patients with CFS have markedly reduced cardiac mass and blood pool volumes, particularly end-diastolic volume: this results in significant impairments in stroke volume and cardiac output compared to controls. The CFS group appeared to have a delay in the release of torsion.


Subject(s)
Cardiac Output/physiology , Fatigue Syndrome, Chronic/diagnosis , Magnetic Resonance Imaging, Cine/methods , Ventricular Dysfunction/diagnosis , Ventricular Function/physiology , Adult , Case-Control Studies , Fatigue Syndrome, Chronic/physiopathology , Female , Humans , Magnetic Resonance Imaging, Cine/standards , Middle Aged , Predictive Value of Tests , Statistics as Topic , Torsion, Mechanical , Ventricular Dysfunction/physiopathology
10.
Diabetologia ; 54(10): 2506-14, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21656330

ABSTRACT

AIMS/HYPOTHESIS: Type 2 diabetes is regarded as inevitably progressive, with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake. METHODS: Eleven people with type 2 diabetes (49.5 ± 2.5 years, BMI 33.6 ± 1.2 kg/m(2), nine male and two female) were studied before and after 1, 4 and 8 weeks of a 2.5 MJ (600 kcal)/day diet. Basal hepatic glucose output, hepatic and peripheral insulin sensitivity and beta cell function were measured. Pancreas and liver triacylglycerol content was measured using three-point Dixon magnetic resonance imaging. An age-, sex- and weight-matched group of eight non-diabetic participants was studied. RESULTS: After 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003). Insulin suppression of hepatic glucose output improved from 43 ± 4% to 74 ± 5% (p = 0.003 vs baseline; controls 68 ± 5%). Hepatic triacylglycerol content fell from 12.8 ± 2.4% in the diabetic group to 2.9 ± 0.2% by week 8 (p = 0.003). The first-phase insulin response increased during the study period (0.19 ± 0.02 to 0.46 ± 0.07 nmol min(-1) m(-2); p < 0.001) and approached control values (0.62 ± 0.15 nmol min(-1) m(-2); p = 0.42). Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min(-1) m(-2)). Pancreatic triacylglycerol decreased from 8.0 ± 1.6% to 6.2 ± 1.1% (p = 0.03). CONCLUSIONS/INTERPRETATION: Normalisation of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone. This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.


Subject(s)
Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/physiopathology , Insulin-Secreting Cells/physiology , Liver/metabolism , Pancreas/metabolism , Triglycerides/metabolism , Adult , Aged , Blood Glucose/metabolism , Body Composition/physiology , Body Weight/physiology , Diabetes Mellitus, Type 2/metabolism , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged
11.
Neurology ; 76(4): 346-53, 2011 Jan 25.
Article in English | MEDLINE | ID: mdl-21263136

ABSTRACT

OBJECTIVE: There are currently no effective treatments to halt the muscle breakdown in Duchenne muscular dystrophy (DMD), although genetic-based clinical trials are being piloted. Most of these trials have as an endpoint the restoration of dystrophin in muscle fibers, hence requiring sufficiently well-preserved muscle of recruited patients. The choice of the muscles to be studied and the role of noninvasive methods to assess muscle preservation therefore require further evaluation. METHODS: We studied the degree of muscle involvement in the lower leg muscles of 34 patients with DMD >8 years, using muscle MRI. In a subgroup of 15 patients we correlated the muscle MRI findings with the histology of open extensor digitorum brevis (EDB) muscle biopsies. Muscle MRI involvement was assigned using a scale 0-4 (normal-severe). RESULTS: In all patients we documented a gradient of involvement of the lower leg muscles: the posterior compartment (gastrocnemius > soleus) was most severely affected; the anterior compartment (tibialis anterior/posterior, popliteus, extensor digitorum longus) least affected. Muscle MRI showed EDB involvement that correlated with the patient's age (p = 0.055). We show a correlation between the MRI and EDB histopathologic changes, with MRI 3-4 grades associated with a more severe fibro-adipose tissue replacement. The EDB was sufficiently preserved for bulk and signal intensity in 18/22 wheelchair users aged 10-16.6 years. CONCLUSION: This study provides a detailed correlation between muscle histology and MRI changes in DMD and demonstrates the value of this imaging technique as a reliable tool for the selection of muscles in patients recruited into clinical trials.


Subject(s)
Muscle, Skeletal/pathology , Muscular Dystrophy, Duchenne/pathology , Adolescent , Child , Foot , Humans , Leg , Magnetic Resonance Imaging , Male , Muscle, Skeletal/physiopathology , Muscular Dystrophy, Duchenne/physiopathology
12.
J Intern Med ; 267(4): 394-401, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20433583

ABSTRACT

OBJECTIVES: To examine muscle acid handling following exercise in chronic fatigue syndrome (CFS/ME) and the relationship with autonomic dysfunction. DESIGN: Observational study. SETTING: Regional fatigue service. SUBJECTS & INTERVENTIONS: Chronic fatigue syndrome (n = 16) and age and sex matched normal controls (n = 8) underwent phosphorus magnetic resonance spectroscopy (MRS) to evaluate pH handling during exercise. Subjects performed plantar flexion at fixed 35% load maximum voluntary contraction. Heart rate variability was performed during 10 min supine rest using digital photophlethysmography as a measure of autonomic function. RESULTS: Compared to normal controls, the CFS/ME group had significant suppression of proton efflux both immediately postexercise (CFS: 1.1 +/- 0.5 mmol L(-1) min(-1) vs. normal: 3.6 +/- 1.5 mmol L(-1) min(-1), P < 0.001) and maximally (CFS: 2.7 +/- 3.4 mmol L(-1) min(-1) vs. control: 3.8 +/- 1.6 mmol L(-1) min(-1), P < 0.05). Furthermore, the time taken to reach maximum proton efflux was significantly prolonged in patients (CFS: 25.6 +/- 36.1 s vs. normal: 3.8 +/- 5.2 s, P < 0.05). In controls the rate of maximum proton efflux showed a strong inverse correlation with nadir muscle pH following exercise (r(2) = 0.6; P < 0.01). In CFS patients, in contrast, this significant normal relationship was lost (r(2) = 0.003; P = ns). In normal individuals, the maximum proton efflux following exercise were closely correlated with total heart rate variability (r(2) = 0.7; P = 0.007) this relationship was lost in CFS/ME patients (r(2) < 0.001; P = ns). CONCLUSION: Patients with CFS/ME have abnormalities in recovery of intramuscular pH following standardised exercise degree of which is related to autonomic dysfunction. This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.


Subject(s)
Fatigue Syndrome, Chronic/metabolism , Muscle, Skeletal/metabolism , Blood Pressure/physiology , Case-Control Studies , Energy Metabolism , Fatigue Syndrome, Chronic/physiopathology , Heart Rate/physiology , Humans , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy/methods , Muscle Contraction/physiology , Phosphorus , Physical Exertion/physiology , Time Factors
13.
Clin Genet ; 74(1): 82-7, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18537981

ABSTRACT

Primary congenital glaucoma (PCG) is a genetically heterogeneous disorder of autosomal recessive inheritance, with mutations in the cytochrome P450 1B1 (CYP1B1) gene detected in an average of approximately 50% of cases worldwide. The Roma/Gypsies are considered to be a rare example of a single founder CYP1B1 mutation, E387K (identified in the Slovak Roma), accounting for 100% of disease alleles. Contrary to this concept, unusual genetic heterogeneity was revealed in this study of 21 Gypsy PCG patients from Bulgaria and 715 controls from the general Gypsy population. In our small sample of affected subjects, we identified five different CYP1B1 mutations - four known (E229K, R368H, E387K and R390C) and one novel and potentially pathogenic (F445I), which together accounted for approximately 30% of disease alleles. E387K was rare in both the patient and the control group, indicating that its high frequency in the Slovak Roma is the product of local founder effect not representative of the overall molecular pattern of PCG in the Gypsy population. Data on other Mendelian disorders and on the population genetics of the Gypsies suggest that a true founder mutation is likely to exist and has remained undetected. Our analysis of another candidate gene, MYOC, and the GLC3B and GLC3C loci did not provide support for their involvement. The molecular basis of PCG in the Gypsies is thus unresolved, and diagnostic analyses should be extended beyond the E387K mutation.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Glaucoma/ethnology , Glaucoma/genetics , Roma/genetics , Aryl Hydrocarbon Hydroxylases , Case-Control Studies , Cytochrome P-450 CYP1B1 , Founder Effect , Glaucoma/congenital , Humans , Mutation
14.
Br J Radiol ; 81(967): 583-6, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18443015

ABSTRACT

MR sialography using heavily T(2) weighted projection techniques relies upon saliva for image contrast, and the visualization of normal ducts is often limited. Methods used to increase the volume of intraductal saliva during imaging in order to improve duct visualization have not been previously evaluated. The effect of a sialogogue and passive ductal occlusion on the ability to visualize the main and intraglandular salivary gland ducts during MR sialography was investigated. Three-dimensional (3D) T(2) weighted MR sialograms were obtained from 12 healthy volunteers with and without the combined use of a sialogogue and passive ductal occlusion pad adjacent to the parotid duct orifice on one side. Two radiologists (in consensus) subjectively evaluated ductal visualization and image artefacts on the resulting blinded maximum intensity projections. The results demonstrate that main duct visualization was significantly improved (p<0.00001) by this technique, with no significant change seen in image artefacts. Although an improvement in intraglandular duct visualization was noted, this was not statistically significant (p = 0.05). Thus, the use of a sialogogue and passive ductal occlusion improves visualization of the main parotid duct in volunteers undergoing MR sialography. Further optimization and evaluation of this approach should lead to improvements in the MR sialography examination of patients.


Subject(s)
Magnetic Resonance Imaging/methods , Parotid Gland/anatomy & histology , Salivary Ducts/anatomy & histology , Sialography/methods , Adult , Artifacts , Constriction , Female , Humans , Male , Middle Aged , Pilot Projects
15.
Br J Radiol ; 79(945): 712-5, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16940371

ABSTRACT

Low carbohydrate diets are currently fashionable for inducing weight loss, but the metabolic effects at organ level are not well understood, especially the effect on liver fat storage. Such studies require serial hepatic fat measurements, for which liver biopsy is impractical. In 10 healthy volunteers we demonstrate the use of rapid (total 2 min acquisition time, 10 min magnet room time), non-invasive, quantitative MRI to serially measure hepatic fat changes induced by following a low carbohydrate diet for 10 days. A significant (p<0.01) reduction in hepatic fat after 3 days of dieting was observed in 5 subjects. All subjects demonstrated significant (p<0.01) reductions in hepatic fat by day 10. A strong correlation (kappa = 0.81) existed between the initial fat content and the percentage fat content reduction in the first 3 days of the diet. All subjects lost weight (average 1.7 kg at day 3 and 3.0 kg at day 10), but this was not correlated with hepatic fat loss after 3 days or 10 days of dieting. The results presented illustrate the potential value of MR hepatic fat quantification in longitudinal studies of hepatic fat content.


Subject(s)
Adipose Tissue/anatomy & histology , Diet, Carbohydrate-Restricted , Liver/anatomy & histology , Adult , Body Mass Index , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Weight Loss
16.
NMR Biomed ; 19(2): 231-5, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16538673

ABSTRACT

Percutaneous liver biopsy is the current gold standard for the diagnosis and assessment of hepatic fibrosis: it is an uncomfortable procedure with associated risks of infection and internal bleeding. Diffusion-weighted MRI may be important as a non-invasive measure of the grade of hepatic fibrosis, owing to the morphological and physiological changes in hepatic tissues as fibrosis develops. The factors that influence hepatic diffusion measurements are complex and are thought to include hepatic perfusion. This study assesses whether hepatic diffusion measurements are influenced by hepatic perfusion changes as this could be an important variable when investigating the relationship between diffusion measurements and grade of hepatic fibrosis. Hepatic apparent diffusion coefficients (ADCs) were measured in 10 healthy volunteers after an 8-h fast and 1-h after a standard meal (which increases portal vein flow and hepatic sinusoidal perfusion) using a breath-hold technique at b-values of 750, 500 and 200 s/mm(2). ADC measurements using b = 750 and 500 s/mm(2) in the posterior right lobe were unaffected by the perfusion changes (P = 0.15 and 0.14, respectively) whereas the results from the anterior right lobe significantly increased post-prandially (P = 0.03 and 0.008, respectively): inter-subject variability was low ( approximately 5%) for these b-values. Portal perfusion had a significant effect in both the posterior and anterior segments of the right lobe when using a b-value of 200 s/mm(2) (P = 0.01 and 0.00001 respectively): inter-subject variability was found to be high ( approximately 25%). The most reproducible measurements of the ADC can be made in the posterior right lobe and the effect of perfusion is minimised at the higher b-values (b = 500 and 750 s/mm(2)).


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Liver Circulation/physiology , Liver/blood supply , Liver/physiology , Perfusion/methods , Portal System/physiology , Adult , Blood Flow Velocity , Female , Humans , Male
17.
J Colloid Interface Sci ; 296(2): 700-9, 2006 Apr 15.
Article in English | MEDLINE | ID: mdl-16257005

ABSTRACT

The migration of emulsion droplets under shear flow remains a largely unexplored area of study, despite the existence of an extensive literature on the analogous problem of solid particle migration. A novel methodology is presented to track the shear-induced migration of emulsion droplets based on magnetic resonance imaging (MRI). The work is in three parts: first, single droplets of one Newtonian fluid are suspended in a second Newtonian fluid (water in silicone oil (PDMS)) and are tracked as they migrate within a Couette cell; second, the migration of emulsion droplets in Poiseuille flow is considered; third, water-in-silicone oil emulsions are sheared in a Couette cell. The effect of (a) rotational speed of the Couette, (b) the continuous phase viscosity, and (c) the droplet phase concentration are considered. The equilibrium extent of migration and rate of migration increase with rotational speed for two different emulsion systems and increased continuous phase viscosity, leads to a greater equilibrium extent of migration. The relationship between the droplet phase concentration and migration is however complex. These results for semi-concentrated emulsion systems and wide-gap Couette cells are not well described by existing models of emulsion droplet migration.

18.
J Magn Reson ; 176(1): 71-8, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15978855

ABSTRACT

Pulsed field gradient (PFG) nuclear magnetic resonance (NMR) is well established as a tool for determining emulsion droplet-size distributions via measurement of restricted self-diffusion. Most measurements made to date have not been spatially resolved, but have measured an average size distribution for a certain volume of emulsion. This paper demonstrates a rapid method of performing spatially resolved, restricted diffusion measurements, which enables emulsion droplet sizing to be spatially resolved as a function of radius in cylindrical geometries or pipes. This is achieved by the use of an Abel transform. The technique is demonstrated in various annular systems containing two emulsions, with different droplet-size distributions, and/or a pure fluid. It is also shown that by modifying the pulse sequence by the inclusion of flow-compensating magnetic field gradients, the technique can measure spatially resolved droplet-size distributions in flowing emulsions, with potential applications in spatially resolved on-line droplet-size analysis.

19.
J Magn Reson ; 171(1): 118-23, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15504689

ABSTRACT

In this paper we describe a new extension to the RARE rapid imaging technique--ROTACOR--which compensates for constant sample rotational motion by rotating the direction of the gradient coordinate system (read and phase directions) between each refocusing RF pulse and therefore between each acquisition of a line of k-space in the read direction. In the laboratory frame this corresponds to an irregularly sampled k-space raster; for a sample rotating at the predefined rotation rate this will correspond to the sampling of a rectilinear k-space raster. This technique is applied to two rotating systems. First, to demonstrate the technique, a rotating mixing paddle in water is imaged using conventional RARE and then using the ROTACOR sequence, demonstrating the improvement of image quality produced by ROTACOR. Second, ROTACOR is used to image the deformation of water droplets in silicone oil, being sheared in a wide-gap Couette cell. Accurate imaging of the droplet shape as a function of shear rate, permits determination of the interfacial tension between the two fluids concerned; the results compare favourably with reported literature values.

20.
J Colloid Interface Sci ; 275(1): 165-71, 2004 Jul 01.
Article in English | MEDLINE | ID: mdl-15158394

ABSTRACT

Various nuclear magnetic resonance (NMR) techniques were used to monitor the freezing behaviour of suspended 2-mm-diameter drops. The drops were composed of hydrocarbon oils emulsified in either water or water/sucrose mixtures. As such they were good model systems for the study of spray freezing, sharing structural similarities with potential products such as ice cream. In particular, simple 1H NMR spectroscopy was used to monitor and individually quantify the freezing or solidification behaviour of the various constituent species of the drops. In addition, the effect of freezing on the emulsion droplet size distribution (and hence emulsion stability) was also measured based on NMR self-diffusion measurements. The effect of freeze/thaw cycling was also similarly studied. The nucleation temperature of the emulsion droplets was found to depend on the emulsion droplet size distribution: the smaller the droplets, the lower the nucleation temperature. Emulsion droplet sizing indicated that oil-in-sucrose-solution emulsions were more stable, showing minimal coalescence, whereas oil-in-water emulsions showed significant coalescence during freezing and freeze/thaw cycling.

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