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Biomedical subjects

M A Thomas

Publications and source records attributed to M A Thomas.

At least 19 recordsLinked to original sources

Cerebral metabolites in HIV-infected children followed for 10 months with 1H-MRS.

BACKGROUND: Previous studies have shown that HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy (1H MRS), but the stability of these measurements over time has not been described in HIV-infected children. The authors recently reported a study of cerebral metabolites in 20 HIV-infected children (6 to 16 years of age); the current study followed 12 of these children (10.0 years +/- 3.7 years) and repeated the MR spectroscopy at 24.1 +/- 3.7 weeks and 42.2 +/- 3.5 weeks following the entry time with repeated neuropsychological testing. METHODS: 1H MR spectra were acquired at 1.5 T (GE Signa, PRESS localization, repetition time = 3,000 msec, echo time = 30 msec). Five brain regions were studied: right frontal white matter, left frontal white matter, right basal ganglia, right hippocampus, and midfrontal gray matter. The concentrations of N-acetylaspartate (NAA), choline (CHO), creatine (CR), and myo-inositol (mI) and the ratio of each metabolite to CR were determined. RESULTS: There were no changes in the metabolite concentrations or metabolite/CR ratios at the three time periods. Similarly, during this follow-up period, HIV-positive children showed no changes in clinical signs, HIV viral loads, CD4%, or CD4 counts, except for improved spatial memory with repeat testing. CONCLUSION: In a clinically and neurologically stable group of HIV-infected children, cerebral metabolites were stable over a 10-month time period, suggesting that it is possible to assess changes in cerebral metabolites as a measure of cerebral health, but longer follow-up in a larger sample is needed.

Adolescent↗

A review of troponin assay performance in Wales: can the same (method-dependent) decision limits be used in different sites?

An audit of troponin measurement protocols in use in Wales showed significant variations in practice with no consensus on analytical methods, or in the selection of a decision limit for the diagnosis of myocardial damage. Peer review data on assay imprecision at concentrations approaching the analytical limit of detection are lacking. The objective of the study was to establish clinically relevant precision profiles for the troponin methods used throughout Wales, which could be used to develop a standardized approach to the selection of a decision limit. A series of five pools of human serum spiked with troponin I-T complex were prepared and stored at -70 degrees C until dispatch. Five sets of each pool were dispatched to all Welsh laboratories and stored at -20 degrees C until analysis. The analysis protocol consisted of two replicates of each pool per batch, and two batches per day for five days (n=20). All the laboratories performed all the measurements in the same week. The lowest concentration providing a 10% coefficient of variation (CV) was 0.02 microg/L for the Roche method and 0.11 microg/L for the Beckman AccuTnI. The lowest concentrations that could be distinguishable from the 99th percentile reference limit were 0.02 microg/L for the Roche method and 0.07 microg/L for the Beckman AccuTnI. Current methods do not achieve the 10% CV at the 99th percentile reference limit proposed by the European Society of Cardiology. Use of the lowest concentration that can be reliably distinguished from the 99th percentile reference limit offers a novel alternative decision limit, which provides a slightly lower concentration than at the 10% CV but maintaining confidence in the assay that false-positive rates will be minimized.

Chemistry, Clinical↗

Recommended standards for biochemical markers of myocardial damage: All Wales Clinical Biochemistry Audit Group.

The effective use of cardiac-specific troponin estimations in the diagnosis of acute myocardial infarction (AMI) is clouded by the imprecise definition surrounding the decision limits. This has led to a wide variation of criteria for the diagnosis of myocardial infarction. A survey of troponin measurements in Welsh laboratories, undertaken in 2003 under the auspices of the All Wales Clinical Biochemistry Audit Group, revealed significant variations in laboratory and clinical practice. Extensive discussion and consultation led by a working group of clinical biochemists and cardiologists in Wales culminated in recommendations concerning the use of troponin assays to establish myocardial damage. The key recommendations are: Cardiac troponin (T or I) should be the first-line test for myocardial damage; Two samples should be collected, at admission and 12-24 h later. The first sample is used for 'rule in' purposes, but not to 'rule out' myocardial damage; Only one threshold (cut-off) value for troponin should be quoted on laboratory reports, values above which are indicative of myocardial damage. A study by the Wales External Quality Assurance Scheme (WEQAS) enabled the derivation of the recommended cut-off concentrations of troponin for defining myocardial damage, defined for each assay as the concentration that can be reliably distinguished, with a confidence interval of 99%, from the 99th percentile reference limit. These recommended standards provide a rationale for a uniform approach for troponin assays for patients with chest pain, working towards a standardized approach to the diagnosis and management of patients presenting with acute coronary syndromes.

Biomarkers↗

Ocular photodynamic therapy with verteporfin for choroidal neovascularization secondary to ocular histoplasmosis syndrome.

PURPOSE: To evaluate the use of ocular photodynamic therapy (OPT) with verteporfin in patients with choroidal neovascularization (CNV) from ocular histoplasmosis syndrome (OHS) and to compare these results with those for a natural history group. METHODS: A retrospective chart review was performed to identify cases of CNV secondary to OHS treated with OPT. Complete data were available for 38 of 41 eligible eyes. Data regarding the following variables were abstracted from the patient charts: demographic characteristics, previous surgery, angiographic features, number and timing of treatments with OPT, follow-up time, and visual acuity. The visual acuity results of eyes receiving photodynamic therapy were compared with those for a natural history cohort. RESULTS: On average, OHS patients who received treatment developed 0.88 line of visual improvement. Visual acuity improved or stayed the same in 69% (22 of 32) of eyes, improved by > or = 2 lines in 44% (14 of 32), and improved by > or = 4 lines in 22% (7 of 32). Patients who received OPT were 2.07 times more likely to have improved or constant vision than were those in the natural history group as described in one retrospective series (odds ratio = 2.07; 95% confidence interval, 0.78-5.56; P = 0.162). Thirty-eight percent (12 of 32) of eyes had undergone submacular surgery for CNV before any OPT. CONCLUSIONS: Ocular photodynamic therapy with verteporfin may be beneficial in patients with CNV secondary to OHS, even in the setting of previous submacular surgery.

Adolescent↗

Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression.

The epithelial Na(+) channel (ENaC) plays an essential role in the regulation of whole body Na(+) balance and blood pressure. The cell surface expression of this channel, a complex of three subunits (alpha, beta and gamma ENaC), has been shown to be regulated by hormones such as aldosterone and vasopressin and by intracellular signaling, including ubiquitylation and/or phosphorylation. However, the molecular mechanisms involving phosphorylation in the regulation of ENaC are unclear. Here we show by expression studies in Xenopus laevis oocytes that the aldosterone-induced Sgk1 kinase interacts with the ubiquitin protein ligase Nedd4-2 in a PY motif-dependent manner and phosphorylates Nedd4-2 on Ser444 and, to a lesser extent, Ser338. Such phosphorylation reduces the interaction between Nedd4-2 and ENaC, leading to elevated ENaC cell surface expression. These data show that phosphorylation of an enzyme involved in the ubiquitylation cascade (Nedd4-2) controls cell surface density of ENaC and propose a paradigm for the control of ion channels. Moreover, they suggest a novel and complete signaling cascade for aldosterone-dependent regulation of ENaC.

Amino Acid Sequence↗

Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) was used to assess neurochemical brain changes across the menstrual cycle in five women with premenstrual dysphoric disorder (PMDD) and six control subjects. Women with PMDD and control subjects were scanned on days 8 and 26 within one menstrual cycle (i.e. at times of complete absence and height of PMDD symptoms, respectively). The point resolved spectroscopic sequence (PRESS) was used to localize a voxel of 8 ml in the medial frontal gray matter and in the occipito-parietal white matter. The ratio of N-acetyl-aspartate to creatine in the region of the medial prefrontal cortex and the cingulate gyrus declined significantly from the follicular to the luteal phase in both groups of subjects. The menstrual phase-dependent significant increase in the ratio of choline to creatine was observed in the parietal white matter. The myo-inositol/creatine ratio exhibited a trend toward higher levels in the PMDD patients in the luteal phase of the menstrual cycle. Differences between PMDD and control subjects were not statistically significant. Menstrual cycle phase-dependent changes in ovarian hormonal concentrations may influence the neurochemistry of brain activity in premenopausal women.

Adolescent↗

Volume-localized two-dimensional correlated magnetic resonance spectroscopy of human breast cancer.

A localized 2D correlation spectroscopic sequence (L-COSY) was implemented and applied in human breast cancer in vivo to evaluate the water to fat (both saturated and unsaturated) ratios and also to identify choline. Being in agreement with the conventional 1D magnetic resonance spectroscopy (MRS) results, elevated water to lipids ratios were found in breast cancers and choline was observed only in a few cancer patients.

Adult↗

Localized two-dimensional shift correlated MR spectroscopy of human brain.

A two-dimensional (2D) chemical shift correlated MR spectroscopic (COSY) sequence integrated into a new volume localization technique (90 degrees -180 degrees -90 degrees ) is proposed for whole-body MR spectroscopy (MRS). Using the product operator formalism, a theoretical calculation of the volume localization as well as the coherence transfer efficiencies in 2D MRS is presented. Phantom model solutions were used to test and optimize the efficiency of the proposed sequence. A combination of different MRI transmit/receive RF coils was used: a head MRI coil and a 3" surface coil receive combined with a body coil transmit. The J cross-peaks due to N-acetyl aspartate (NAA), glutamate/glutamine (Glx), myo-inositol (mI), creatine (Cr), choline (Ch), aspartate (Asp), gamma-aminobutyrate (GABA), taurine (Tau), glutathione (GSH), threonine (Thr), and macromolecules (MM) were identified. The cross-peak intensities excited by the proposed 2D sequence were asymmetric with respect to the diagonal peaks. Localized COSY (L-COSY) spectra of cerebral prefrontal and occipital gray/white matter regions in 15 healthy controls are presented. Magn Reson Med 46:58-67, 2001.

Adult↗

Limited macular translocation for the management of subfoveal retinal pigment epithelial loss after submacular surgery.

PURPOSE: To report a case of subfoveal retinal pigment epithelial (retinal pigment epithelium) loss after submacular surgery managed successfully by limited macular translocation. METHODS: Case report. RESULTS: A 28-year-old woman presented with a visual acuity of 20/100 caused by subfoveal choroidal neovas-cularization secondary to ocular histoplasmosis syndrome. Submacular resection of the choroidal neovascularization was complicated by inadvertent retinal pigment epithelium loss from beneath the foveal center. She underwent limited macular translocation 5 days after the initial surgery and had successful displacement of the fovea to an area inferior to the retinal pigment epithelium defect. Her visual acuity was 20/60 4 months postoperatively. CONCLUSION: This report demonstrates the feasibility of using limited macular translocation for the management of eyes with central retinal pigment epithelium defect after submacular surgery and extends the clinical indications for limited macular translocation.

Adult↗

Macular translocation: unifying concepts, terminology, and classification.

PURPOSE: To describe some unifying concepts, terminology, and classification of macular translocation so as to facilitate communication within the scientific community. METHODS: A panel of ophthalmologists with expertise in macular translocation reviewed available data and developed some unifying concepts, terminology, and classification of macular translocation. RESULTS: Macular translocation may be defined as any surgery that has a primary goal of relocating the central neurosensory retina or fovea intraoperatively or postoperatively specifically for the management of macular disease. It may be classified according to the size of the retinotomy and, where applicable, the technique of chorioscleral shortening used. The direction of macular translocation is denoted by the movement of the neurosensory macula relative to the underlying tissues. Effective macular translocation may be defined as successful intraoperative or postoperative relocation of the fovea overlying a subfoveal lesion to an area outside the border of the lesion. The concepts of minimum desired translocation and median postoperative foveal displacement can give some useful idea of the likelihood of effective macular translocation before surgery. CONCLUSIONS: Use of a common standardized terminology for macular translocation will facilitate communication within the scientific community and enhance further research in this area. However, the definitions, terms, classification, and concepts concerning macular translocation are likely to continue to evolve as macular translocation undergoes further modifications and refinements.

Humans↗

An evaluation of the performance of blood gas analysis in the UK using tonometered haemolysate material.

WEQAS is one of the largest and the most rapidly expanding national EQA Schemes in the UK with over 500 participants. Since April 1995, the Scheme has distributed a tonometered protein-based aqueous material for blood gas analytes (H(+), pCO2, pO2), electrolytes, glucose and lactate. Current performance of the new generation of blood gas analysers show marked bias between analysers which a number of manufacturers have attributed to a "matrix" effect. This study was undertaken to investigate the "true" analytical performance of these analysers utilising a tonometered haemolysate blood product with oxygen saturation kinetics identical to that of fresh blood. One hundred laboratories that represented the major analyzers used in the UK were selected to participate in the study. Participants were asked to analyse the samples within 1 week of tonometry of the material. Performance data, expressed as interlaboratory variation, was compared with concentration matched data from the same group using the aqueous material. Significant improvement in instrument Bias was observed for the AVL Omni and iStat analysers for pO2). Surprisingly, there was also an improvement in bias for the electrolyte parameters on the IL synthesis. However, a significant positive bias was observed for the AVL Opti for Potassium and for the Nova analyzer for glucose using this material. Similar performance was observed for the co-oximetry, parametres for fresh and lyophilised material for the majority of analyzers.

Blood Gas Analysis↗

Decreased anterior cingulate myo-inositol/creatine spectroscopy resonance with lithium treatment in children with bipolar disorder.

This project was designed to compare differences in brain proton spectra between children and adolescents with bipolar disorder (BPD) and gender and age-matched normal controls, and to measure changes in myo-inositol levels following lithium therapy, utilizing in vivo proton magnetic resonance spectroscopy (1H MRS). A single voxel (2x2x2 cm3) was placed in brain anterior cingulate cortex for acquisition of the 1H spectra at baseline and after acute (7 days) lithium administration in 11 children (mean age 11.4 years) diagnosed with BPD, and in 11 normal controls. Acute lithium treatment was associated with a significant reduction in the myo-inositol/creatine ratio. This decrement was also significant in lithium-responders when analyzed separate from non-responders. Compared to normal controls, BPD subjects showed a trend towards a higher myo-inositol/creatine during the manic phase. These preliminary data provide evidence that a significant reduction in anterior cingulate myo-inositol magnetic resonance may occur after lithium treatment, especially among responders. Follow-up studies involving a larger sample may allow us to confirm whether changes in myo-inositol associated with acute lithium therapy persist in long-term clinical response of patients with and without lithium compliance.

Adolescent↗

Vascular function of the peripheral circulation in patients with nephrosis.

BACKGROUND: Nephrotic syndrome is associated with abnormal lipoprotein metabolism and increased risk of coronary heart disease. Endothelial dysfunction, an early phase of atherogenesis that manifests as impaired flow-mediated dilation (FMD) of the peripheral circulation, may link these associations. METHODS: We examined endothelial function of the brachial artery and forearm resistance arteries in 15 patients with nephrosis (NP), 15 patients with primary hyperlipidemia (HL) alone, and 15 normolipidemic, nonproteinuric subjects (NC) matched for age, sex, and weight. The NP and HL groups had similar serum cholesterol and triglyceride concentrations. Post-ischemic FMD (endothelium-dependent) and glyceryl trinitrate-mediated dilation (GTNMD; endothelium-independent) of the brachial artery were studied using ultrasonography and computerized edge detection software. Postischemic forearm blood flow was also measured using plethysmography. RESULTS: Postischemic FMD of the brachial artery was significantly lower in the NP and HL groups compared with NC group (mean +/- SE): NP 4.91 +/- 0.8%, HL 4.53 +/- 0.6%, NC 8.45 +/- 0.5% (P < 0.001). There were no significant differences among the groups in baseline diameter and GTNMD of the brachial artery, nor in maximal forearm blood flow and flow debt repayment of the forearm microcirculation. Significant differences in FMD among the groups were principally related to differences in serum low-density lipoprotein cholesterol. CONCLUSIONS: Patients with NP have abnormal endothelium-dependent but preserved endothelium-independent dilation of the brachial artery following an ischemic stimulus. Postischemic forearm microcirculatory function is unimpaired. Dyslipoproteinemia is probably the principal cause of endothelial dysfunction of conduit arteries in patients with NP and the basis for their increased risk of cardiovascular disease.

Adult↗

Racial and economic demographics of couples seeking infertility treatment.

OBJECTIVE: We characterized new infertility patients on the basis of race and economic factors. STUDY DESIGN: A retrospective chart review was performed of all patients seeking infertility evaluation from 1998 to 1999 at two infertility centers in Cincinnati, Ohio. Patients were categorized by race (white, black, or other). Statistics were analyzed by chi2 and logistic regression. RESULTS: Of 756 patients, 85.2% were white, 10.2% were black, and 4.4% were other. Infertility diagnoses were placed into the following 7 categories: ovarian, salpingitis, surgical sterilization, male factor, endometriosis, unexplained, and other. Black women had significantly more salpingitis than did nonblack women (P <.001) regardless of insurance status. However, surgical sterilization was more prevalent in patients without insurance regardless of race (P <.001). CONCLUSIONS: Our findings are consistent with previous studies showing that black women have more risk factors for salpingitis. Surgical sterilization risk factors were concordant with those of the National Center for Health Statistics.

Black or African American↗

Molecular phylogenetic analysis of evolutionary trends in stonefly wing structure and locomotor behavior.

Insects in the order Plecoptera (stoneflies) use a form of two-dimensional aerodynamic locomotion called surface skimming to move across water surfaces. Because their weight is supported by water, skimmers can achieve effective aerodynamic locomotion even with small wings and weak flight muscles. These mechanical features stimulated the hypothesis that surface skimming may have been an intermediate stage in the evolution of insect flight, which has perhaps been retained in certain modern stoneflies. Here we present a phylogeny of Plecoptera based on nucleotide sequence data from the small subunit rRNA (18S) gene. By mapping locomotor behavior and wing structural data onto the phylogeny, we distinguish between the competing hypotheses that skimming is a retained ancestral trait or, alternatively, a relatively recent loss of flight. Our results show that basal stoneflies are surface skimmers, and that various forms of surface skimming are distributed widely across the plecopteran phylogeny. Stonefly wings show evolutionary trends in the number of cross veins and the thickness of the cuticle of the longitudinal veins that are consistent with elaboration and diversification of flight-related traits. These data support the hypothesis that the first stoneflies were surface skimmers, and that wing structures important for aerial flight have become elaborated and more diverse during the radiation of modern stoneflies.

Animals↗