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Biomedical subjects

T Nelson

Publications and source records attributed to T Nelson.

At least 19 recordsLinked to original sources
PubMed2006

Prenatal detection of associated anomalies in fetuses diagnosed with cleft lip with or without cleft palate in utero.

OBJECTIVE: The aim of this study was to determine the prenatal detection rate of associated anomalies in fetuses with a suspected cleft lip with or without cleft palate. METHODS: Fetuses with a suspected cleft lip with or without cleft palate, determined by prenatal ultrasound, were prospectively enrolled. Additional anomalies suspected by ultrasound or genetic testing were recorded. Postnatal outcome was obtained. RESULTS: Forty-five fetuses with a cleft lip with or without cleft palate, diagnosed prenatally with either two-dimensional and/or three-dimensional ultrasound, were studied. Postnatal follow-up revealed that 16 (35.6%) of these 45 fetuses had an additional structural or syndromic abnormality. Of the 37 fetuses with prenatally determined 'isolated' cleft lip with or without cleft palate, eight (21.6%) had an additional malformation identified after delivery. CONCLUSION: In pregnancies complicated by a cleft lip with or without cleft palate, patients should be informed of the risks of associated anomalies, some of which may be undetected prenatally.

Abnormalities, Multiple↗
PubMed2005

Loss of the transcription factor p45 NF-E2 results in a developmental arrest of megakaryocyte differentiation and the onset of a high bone mass phenotype.

NF-E2 is a transcription factor required for megakaryocyte differentiation. The phenotype of mice deficient in p45 NF-E2 has been characterized by increased numbers of immature megakaryocytes and the absence of functional platelets. These mice also exhibited a high bone mass phenotype with up to a 6-fold increase in trabecular bone volume and a 3- to 5-fold increase in the bone formation rate. Our data indicated that both osteoblast and osteoclast numbers were increased in vivo with a 4- to 10-fold increase in osteoblast number/tissue area and approximately a 5-fold increase in osteoclast number/tissue area. Serum osteocalcin levels were also increased in NF-E2-deficient mice, corroborating the histomorphometric data and confirming that the osteoblasts were functional. Urinary cross-links levels were measured to confirm osteoclast activity. Interestingly, the increased bone was observed only in bony sites of hematopoiesis, and was not seen in flat bones such as calvariae. We showed that cells of the osteoblast lineage do not express NF-E2 mRNA. The increased bone phenotype was adoptively transferred into irradiated wild-type mice using spleen cells from NF-E2-deficient mice. These observations suggest that a megakaryocyte-osteoblast interaction occurs which is anabolic for bone.

Animals↗
PubMed2004

Does diagnosis determine delivery? The Islington study of older people's needs and health care costs.

BACKGROUND: Little is known about the factors associated with the receipt of care by older people. This study investigates the use. costs and factors associated with service usage among people aged 65 or older living in inner London. METHOD: A community-based survey, using questionnaires, examined psychiatric and physical morbidity, formal and informal care. The relationships between demographic, pathological features and the costs of health and social care were explored using multivariate regression. RESULTS: A total of 1085 people were interviewed at home of these 18% did not receive any service at all. The total cost of services per week for people with dementia was pound 109, with activity limitation pound 14 and with depression pound 12. The greatest effect of physical limitation was on the receipt of social care. Dementia had the strongest effect on receipt of social care services. Depression increased health care costs to a much greater degree than social care costs. Despite presenting to services, black elders received significantly less health care than other people with the same needs. Older people living alone were more likely to receive social care support and appeared less likely to use health services. CONCLUSIONS: Physical dependency significantly affects both health and social care costs. Increasing cognitive impairment mainly leads to increasing social care costs. Overall costs are increased by physical dependency, dementia, depression, subjective health problems, living alone and are negatively affected by being black.

Activities of Daily Living↗
PubMed2002

Detection of fenspiride and identification of in vivo metabolites in horse body fluids by capillary gas chromatography-mass spectrometry: administration, biotransformation and urinary excretion after a single oral dose.

Studies related to the in vivo biotransforrmation and urinary excretion of fenspiride hydrochloride in the horse are described. After oral administration, the drug is metabolised by both phase I functionalisation and phase II conjugation pathways. Following enzymatic deconjugation, fenspiride and its phase I metabolites were isolated from post-administration biofluids using bonded co-polymeric mixed mode solid-phase extraction cartridges to isolate the basic compounds. Following trimethylsilylation (TMS), the parent drug and metabolites were identified by capillary gas chromatography-mass spectrometry (GC-MS). Fenspiride (A) and seven metabolites (B-->G) arising from oxidation on both the aromatic and heterocyclic substructures were detected in urine. The positive ion electron ionisation mass spectra of the TMS derivatives of fenspiride and its metabolites provided useful information on its metabolism. Positive ion methane chemical ionisation-GC-MS of the derivatives provided both derivatised molecular mass and structural information. Unchanged fenspiride can be detected in post-administration plasma and urine samples for up to 24 h. Maximum urinary levels of 100-200 ng ml(-1) were observed between 3 and 5 h after administration. After enzymatic deconjugation, the major phenolic metabolite (G) can be detected in urine for up to 72 h. This metabolite is the analyte of choice in the GC-MS screening of post-race equine urine samples for detection of fenspiride use. However, a distinct difference was observed in the urinary excretion of this metabolite between the thoroughbred horses used in UK study and the quarterbred and standardbred horses used for the USA administrations.

Animals↗
PubMed2002

Novel skeletal muscle ryanodine receptor mutation in a large Brazilian family with malignant hyperthermia.

Malignant hyperthermia (MH) is an autosomal dominant disorder that predisposes susceptible individuals to a potentially life-threatening crisis when exposed to commonly used anesthetics. Mutations in the skeletal muscle calcium release channel, ryanodine receptor (RYR1) are associated with MH in over 50% of affected families. Linkage analysis of the RYR1 gene region at 19q13 was performed in a large Brazilian family and a distinct disease co-segregating haplotype was revealed in the majority of members with diagnosis of MH. Subsequent sequencing of RYR1 mutational hot spots revealed a nucleotide substitution of C to T at position 7062, causing a novel amino acid change from Arg2355 to Cys associated with MH in the family. Haplotype analysis of the RYR1 gene area at 19q13 in the family with multiple MH members is an important tool in identification of genetic cause underlying this disease.

Amino Acid Substitution↗
PubMed2001

Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.

BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.

Adult↗
PubMed2001

An association between plasma free protein s concentration and risk of coronary heart disease in middle-aged men.

Protein S is a vitamin K-dependent protein with anticoagulant properties. Case series have reported reduced plasma concentrations in patients with arterial thromboses, while other studies have reported increased levels in patients with coronary heart disease (CHD). The present study sought to clarify the relation between free protein S and risk of CHD. A prospective survey was conducted of 3000 men aged 50 to 61 years, free of clinical CHD at baseline. Free protein S was measured by commercial immunoassay. End-points recorded were sudden coronary death, first nonfatal and fatal myocardial infarction (MI), surgical intervention for symptomatic, angiographically demonstrated CHD, and all-causes mortality. Statistical analysis employed univariate incidence rate ratios followed by Cox proportional hazards regression. There were 168 CHD events recorded during 21,000 person-years of risk. Mean free protein S concentration was 6% higher in those who developed CHD than in the remainder, the crude hazard ratio (HR) for a one standard deviation (S.D.) increase in free protein S being 1.25 (95% CI, 1.08-1.25). Free protein S was associated with cholesterol concentration and other conventional CHD risk factors. In multivariate regression analysis, after adjustment for conventional CHD risk factors a 1 S.D. increase in free protein S was associated with a HR of 1.15 (0.98-1.35) for CHD, of borderline conventional statistical significance. This association of free protein S with risk of CHD may reflect effects of plaque-destabilising inflammatory activity on protein S levels.

Analysis of Variance↗
PubMed2001

Pavlovian conditioning-specific increases of the Ca2+- and GTP-binding protein, calexcitin in identified Hermissenda visual cells.

Hermissenda CNS, immunolabeled for the memory protein calexcitin showed significant immunostaining over background in the B-photoreceptor cells of the eye. The degree of staining correlated positively with the number of Pavlovian training events experienced by the animals and the degree of Pavlovian conditioning induced. The training regime consisted of exposing animals to light (conditioned stimulus, CS) paired with orbital rotation (unconditioned stimulus, US). In animals that exhibited the conditioned response, calexcitin immunolabeling was more intense than was found for naive (unconditioned) animals or animals given the CS and US in random sequence. Animals exposed to lead (maintained in 1.2 ppm lead acetate) at a dosage known to impair learning in children, showed reduced learning and less intense calexcitin staining whether the CS and US were paired or given randomly. However, the levels were still higher than that of naive animals. Immuno-electron microscopy indicated that the labeling was predominantly within calcium sequestering organelles such as the endoplasmic reticulum, and to lesser extent within mitochondria, and photopigments. The calexcitin density after a short-term memory (STM) regime was the same whether measured 5 minutes after conditioning (when STM was evidenced by foot contraction) or 90 minutes later when no recall was detected. The staining density was also similar to the levels found 5 minutes after long-term memory (LTM) conditioning. However, the LTM regime produced a greater calexcitin intensity at 90 minutes when the memory had been consolidated. This learning-specific increase in calexcitin is consistent with the previously implicated sequence of molecular events that are associated with progressively longer time domains of memory storage.

Animals↗
PubMed2001

Stability of dopamine and epinephrine solutions up to 84 hours.

OBJECTIVES: The current practice of preparing fresh dopamine and epinephrine solutions every 24 hrs may lead to hemodynamic instability caused by the interruption of infusions with each change. We determined the stability of these catecholamines over an 84-hr period and whether stability was enhanced by dextrose-containing solutions. SETTING: Tertiary care teaching hospital. DESIGN: The stability of dopamine and epinephrine, each at three commonly used concentrations, was studied in three vehicles (10 gm/dl dextrose in water [D10W], 5 gm/dl dextrose in water [D5W], and 0.9% NaCl in water [NS]). To mimic clinical conditions, solutions were placed on syringe pumps infusing continuously into a closed system at ambient temperature for 84 hrs. MEASUREMENTS: Concentrations of dopamine in mg/ml and epinephrine in microg/ml were measured by high-performance liquid chromatography at 0, 24, 36, 48, 72, and 84 hrs. RESULTS: Dopamine and epinephrine concentrations did not change over the 84-hr period regardless of the vehicles in which the drugs were prepared. CONCLUSIONS: Clinically relevant concentrations of dopamine and epinephrine remain stable in dextrose- and saline-containing solutions for >or=84 hrs. These data suggest that solutions of these catecholamines may safely be used in clinical practice beyond the currently recommended 24 hrs.

Journal Article↗
PubMed2001

Specification of bundle sheath cell fates during maize leaf development: roles of lineage and positional information evaluated through analysis of the tangled1 mutant.

In leaves of the maize tangled1 (tan1) mutant, clusters of bundle sheath (BS)-like cells extend several cells distant from the veins, in association with the single layer of BS cells around the vein. We show that the BS-like cell clusters in tan1 leaves result from the continued division of cells in the procambial/BS cell lineage that do not divide further in wild-type leaves. The ectopic BS-like cells accumulate the BS marker NADP-dependent malic enzyme but not the mesophyll cell marker phosphoenolpyruvate carboxylase, and exhibit thickened walls, suggesting that they differentiate as C4-type BS cells. We propose that bundle sheath cell fate can be conferred on some derivatives of procambial cell divisions in a manner that is heritable through multiple cell divisions and is position-independent.

Cell Differentiation↗
PubMed2001

Three-dimensional ultrasonography and assessment of the first-trimester fetus.

We used transvaginal three-dimensional ultrasonography to assess the first-trimester fetus and compared the findings with contemporaneous two-dimensional ultrasonographic studies. Multiplanar three-dimensional ultrasonography provided good visualization of fetal anatomy and allowed fetal measurement and assessment of nuchal translucency thickness. Three-dimensional ultrasonography required significantly less time to perform and to interpret than two-dimensional ultrasonography. Three-dimensional ultrasonography is an effective means of assessing the first-trimester fetus and offers potential advantages over two-dimensional ultrasonography.

Anthropometry↗
PubMed2000

Intravenous iron dextran and erythropoietin use in pediatric hemodialysis patients.

Recombinant human erythropoietin (rHuEPO) is an effective treatment for the anemia of chronic renal failure. However, adequate availability of iron is necessary for an optimal response. We prospectively evaluated the effect of an intravenous iron protocol in a pediatric hemodialysis unit. Patients with either a serum ferritin less than 150 ng/ml or transferrin saturation (TSAT) less than 20% received intravenous iron dextran during ten consecutive dialysis sessions. The administration of rHuEPO was adjusted using a protocol designed to maintain patient hematocrit between 33% and 36%. Thirteen courses of intravenous iron were evaluated. Patients received 4 mg/kg of iron dextran (maximum of 100 mg) during each of ten consecutive dialysis sessions. In 12 cases there was a decrease in rHuEPO use 2 months after completing the course of intravenous iron. The mean rHuEPO dose decreased from 3,784 units to 2,115 units (P<0.005). Based on the criteria of response to intravenous iron, a percentage iron saturation of less than 20% had a high specificity for detecting iron deficiency. All patients who received a course of intravenous iron had a TSAT less than 20%. The measurement of serum ferritin was less useful in our patients.

Adolescent↗
PubMed1999

The CACC box and myocyte enhancer factor-2 sites within the myosin light chain 2 slow promoter cooperate in regulating nerve-specific transcription in skeletal muscle.

Previous experiments showed that activity of the -800-base pair MLC2slow promoter was 75-fold higher in the innervated soleus (SOL) compared with the noninnervated SOL muscles. Using in vivo DNA injection of MLC2slow promoter-luciferase constructs, the aim of this project was to identify regulatory sites and potential transcription factors important for slow nerve-dependent gene expression. Three sites within the proximal promoter (myocyte enhancer factor-2 (MEF2), E-box, and CACC box) were individually mutated, and the effect on luciferase expression was determined. There was no change in luciferase expression in the SOL and extensor digitorum longus (EDL) muscles when the E-box was mutated. In contrast, the MEF2 mutation resulted in a 30-fold decrease in expression in the innervated SOL muscles (10.3 versus 0.36 normalized relative light units (RLUs)). Transactivation of the MLC2slow promoter by overexpressing MEF2 was only seen in the innervated SOL (676,340 versus 2,225,957 RLUs; p < 0.01) with no effect in noninnervated SOL or EDL muscles. These findings suggest that the active MLC2slow promoter is sensitive to MEF2 levels, but MEF2 levels alone do not determine nerve-dependent expression. Mutation of the CACC box resulted in a significant up-regulation in the EDL muscles (0.23 versus 4.08 normalized RLUs). With the CACC box mutated, overexpression of MEF2 was sufficient to transactivate the MLC2slow promoter in noninnervated SOL muscles (27,536 versus 1, 605,797 RLUs). Results from electrophoretic mobility shift and supershift assays confirm MEF2 protein binding to the MEF2 site and demonstrate specific binding to the CACC sequence. These results suggest a model for nerve-dependent regulation of the MLC2slow promoter in which derepression occurs through the CACC box followed by quantitative expression through enhanced MEF2 activation.

Animals↗
PubMed1999

ROUGH SHEATH2: a Myb protein that represses knox homeobox genes in maize lateral organ primordia.

The regulation of members of the knotted1-like homeobox (knox) gene family is required for the normal initiation and development of lateral organs. The maize rough sheath2 (rs2) gene, which encodes a Myb-domain protein, is expressed in lateral organ primordia and their initials. Mutations in the rs2 gene permit ectopic expression of knox genes in leaf and floral primordia, causing a variety of developmental defects. Ectopic KNOX protein accumulation in rs2 mutants occurs in a subset of the normal rs2-expressing cells. This variegated accumulation of KNOX proteins in rs2 mutants suggests that rs2 represses knox expression through epigenetic means.

Amino Acid Sequence↗
PubMed1999

Genetic regulation of vascular tissue patterning in Arabidopsis.

Plants transport water and nutrients through a complex vascular network comprised of interconnected, specialized cell types organized in discrete bundles. To identify genetic determinants of vascular tissue patterning, we conducted a screen for mutants with altered vascular bundle organization in Arabidopsis cotyledons. Mutations in two genes, CVP1 and CVP2 (for cotyledon vascular pattern), specifically disrupt the normal pattern of vascular bundles in cotyledons, mature leaves, and inflorescence stems. The spatial distribution of the procambium, the precursor to mature vascular tissue, is altered in cvp1 and cvp2 embryos, suggesting that CVP1 and CVP2 act at a very early step in vascular patterning. Similarly, in developing stems of cvp1 and leaves of cvp2, the pattern of vascular differentiation is defective, but the maturation of individual vascular cells appears to be normal. There are no discernible alterations in cell morphology in cvp2 mutants. In contrast, cvp1 mutants are defective in directional orientation of the provascular strand, resulting in a failure to establish uniformly aligned vascular cells, and they also show a reduction in vascular cell elongation. Neither cvp1 nor cvp2 mutants displayed altered auxin perception, biosynthesis, or transport, suggesting that auxin metabolism is not generally affected in these mutants.

Arabidopsis↗
PubMed1999

Real-time three-dimensional fetal echocardiography: initial feasibility study.

Real-time three-dimensional echocardiography acquires data as a volume rather than as a series of planar images, thereby obviating cardiac or respiratory gating and limiting artifacts generated by random motion. This study was undertaken to evaluate the feasibility of using real-time three-dimensional echocardiography to evaluate fetal cardiac anatomy and function. Ten human fetuses were evaluated in utero, four of whom had congenital heart disease. Freehand transabdominal scanning was performed on each pregnant woman using a real-time three-dimensional echocardiography system. Four volume clips at 20 volumes/s of duration 1.5 s each were obtained on each fetal heart and stored for off-line analysis. Data were displayed immediately as a series of four simultaneous planes, with the ability for the observer to manipulate the position of each plane within the acquired volume data set. Cardiac motion could be slowed, stopped, or viewed at its original speed. Most structures and views, as well as cardiac function, could be visualized consistently. Abnormal structures could be detected readily. Off-line analysis was rapid and easy. We conclude that fetal real-time three-dimensional echocardiography is a feasible, facile, and rapid new technique.

Echocardiography, Three-Dimensional↗