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Biomedical subjects

A Thomas

Publications and source records attributed to A Thomas.

At least 19 recordsLinked to original sources

[Renal transplant: color duplex ultrasound and contrast-enhanced ultrasound in the evaluation of the early postoperative phase and surgical complications].

Contrast ultrasound is a promising and straightforward method that is superior to established sonographic techniques such as conventional B-mode scanning which is used for volume measurement and hematoma demonstration. Color Doppler is important for the evaluation of rejection, the detection of perfusion defects, and complete vascularization in the diagnostic evaluation of kidney grafts. Moreover, contrast US has the potential for tumor characterization in transplanted kidneys. A single examination by contrast ultrasound can answer a variety of questions with respect to the early postoperative phase and chronic damage. New applications of contrast US will arise from the further technical development of ultrasound equipment. The rapid technical advances seen in recent years have been followed by the introduction of new software tools for the analysis of raw datasets or the improved visualization of microbubbles at very low energy. Initial studies show that efficient and early diagnosis of rejection is possible. Surgical complications like perfusion defects or hematoma can also be identified.

Animals↗

Measurement of the Gerasimov-Drell-Hearn Integrand for 2H from 200 to 800 MeV.

A measurement of the helicity dependence of the total inclusive photoabsorption cross section on the deuteron was carried out at MAMI (Mainz) in the energy range 200<Egamma<800 MeV. The experiment used a 4pi detection system, a circularly polarized tagged photon beam and a frozen-spin target which provided longitudinally polarized deuterons. The contribution to the Gerasimov-Drell-Hearn sum rule for the deuteron determined from the data is 407+/-20(stat)+/-24(syst) mu b for 200<Egamma<800 MeV.

Journal Article↗

The effect of breathing an ambient low-density, hyperoxic gas on the perceived effort of breathing and maximal performance of exercise in well-trained athletes.

BACKGROUND: The role of the perception of breathing effort in the regulation of performance of maximal exercise remains unclear. AIMS: To determine whether the perceived effort of ventilation is altered through substituting a less dense gas for normal ambient air and whether this substitution affects performance of maximal incremental exercise in trained athletes. METHODS: Eight highly trained cyclists (mean SD) maximal oxygen consumption (VO(2)max) = 69.9 (7.9) (mlO(2)/kg/min) performed two randomised maximal tests in a hyperbaric chamber breathing ambient air composed of either 35% O(2)/65% N(2) (nitrox) or 35% O(2)/65% He (heliox). A ramp protocol was used in which power output was incremented at 0.5 W/s. The trials were separated by at least 48 h. The perceived effort of breathing was obtained via Borg Category Ratio Scales at 3-min intervals and at fatigue. Oxygen consumption (VO(2)) and minute ventilation (V(E)) were monitored continuously. RESULTS: Breathing heliox did not change the sensation of dyspnoea: there were no differences between trials for the Borg scales at any time point. Exercise performance was not different between the nitrox and heliox trials (peak power output = 451 (58) and 453 (56) W), nor was VO(2)max (4.96 (0.61) and 4.88 (0.65) l/min) or maximal V(E) (157 (24) and 163 (22) l/min). Between-trial variability in peak power output was less than either VO(2)max or maximal V(E). CONCLUSION: Breathing a less dense gas does not improve maximal performance of exercise or reduce the perception of breathing effort in highly trained athletes, although an attenuated submaximal tidal volume and V(E) with a concomitant reduction in VO(2) suggests an improved gas exchange and reduced O(2) cost of ventilation when breathing heliox.

Adult↗

Intraocular implants for extended drug delivery: therapeutic applications.

An overview of ocular implants with therapeutic application potentials is provided. Various types of implants can be used as slow release devices delivering locally the needed drug for an extended period of time. Thus, multiple periocular or intraocular injections of the drug can be circumvented and secondary complications minimized. The various compositions of polymers fulfilling specific delivery goals are described. Several of these implants are undergoing clinical trials while a few are already commercialized. Despite the paramount progress in design, safety and efficacy, the place of these implants in our clinical therapeutic arsenal remains limited. Miniaturization of the implants allowing for their direct injection without the need for a complicated surgery is a necessary development avenue. Particulate systems which can be engineered to target specifically certain cells or tissues are another promising alternative. For ocular diseases affecting the choroid and outer retina, transscleral or intrasscleral implants are gaining momentum.

Animals↗

DYX1C1 functions in neuronal migration in developing neocortex.

Rodent homologues of two candidate dyslexia susceptibility genes, Kiaa0319 and Dcdc2, have been shown to play roles in neuronal migration in developing cerebral neocortex. This functional role is consistent with the hypothesis that dyslexia susceptibility is increased by interference with normal neural development. In this study we report that in utero RNA interference against the rat homolog of another candidate dyslexia susceptibility gene, DYX1C1, disrupts neuronal migration in developing neocortex. The disruption of migration can be rescued by concurrent overexpression of DYX1C1, indicating that the impairment is not due to off-target effects. Transfection of C- and N-terminal truncations of DYX1C1 shows that the C-terminal TPR domains determine DYX1C1 intracellular localization to cytoplasm and nucleus. RNAi rescue experiments using truncated versions of DYX1C1 further indicate that the C-terminus of DYX1C1 is necessary and sufficient to DYX1C1's function in migration. In conclusion, DYX1C1, similar to two other candidate dyslexia susceptibility genes, functions in neuronal migration in rat neocortex.

Analysis of Variance↗

In vitro and in vivo pharmacology of synthetic olivetol- or resorcinol-derived cannabinoid receptor ligands.

BACKGROUND AND PURPOSE: We have previously reported the development of CB-25 and CB-52, two ligands of CB1 and CB2 cannabinoid receptors. We assessed here their functional activity. EXPERIMENTAL APPROACH: The effect of the two compounds on forskolin-induced cAMP formation in intact cells or GTP-gamma-S binding to cell membranes, and their action on nociception in vivo was determined. KEY RESULTS: CB-25 enhanced forskolin-induced cAMP formation in N18TG2 cells (EC50 approximately 20 nM, max. stimulation = 48%), behaving as an inverse CB1 agonist, but it stimulated GTP-gamma-S binding to mouse brain membranes, behaving as a partial CB1 agonist (EC50 =100 nM, max. stimulation = 48%). At human CB1 receptors, CB-25 inhibited cAMP formation in hCB1-CHO cells (EC50 = 1600 nM, max. inhibition = 68% of CP-55,940 effect). CB-52 inhibited forskolin-induced cAMP formation by N18TG2 cells (IC50 = 450 nM, max. inhibition = 40%) and hCB1-CHO cells (EC50 = 2600 nM, max. inhibition = 62% of CP-55,940 effect), and stimulated GTP-gamma-S binding to mouse brain membranes (EC50 = 11 nM, max. stimulation approximately 16%). Both CB-25 and CB-52 showed no activity in all assays of CB2-coupled functional activity and antagonized CP55940-induced stimulation of GTP-gamma-S binding to hCB2-CHO cell membranes. In vivo, both compounds, administered i.p., produced dose-dependent nociception in the plantar test carried out in healthy rats, and antagonised the anti-nociceptive effect of i.p. WIN55,212-2. In the formalin test in mice, however, the compounds counteracted both phases of formalin-induced nociception. CONCLUSIONS AND IMPLICATIONS: CB-25 and CB-52 behave in vitro mostly as CB1 partial agonists and CB2 neutral antagonists, whereas their activity in vivo might depend on the tonic activity of cannabinoid receptors.

Action Potentials↗

Visual hallucinations in Parkinson's disease: clues to separate origins.

Our paper discusses two experimental studies suggesting that Visual Hallucinations (VH) in Parkinson's Disease (PD) may have separate origins. The first is a prospective 8years study evaluating the appearance of VH, visual abnormalities assessed by Visual Evoked Potentials (VEPs) and REM sleep Behaviour Disorder (RBD), in 80 PD patients treated with l-Dopa and Dopaminoagonists (DA). In chronically treated, cognitively unimpaired, PD patients VH were statistically related (p=0.001) to RBD occurrence and high DA doses. Visual abnormalities were significantly reduced by l-Dopa or DA intake, and were statistically unrelated to VH. The second study involved PD patients placed in a Virtual Reality Environment, to decontextualize visual input. When motor symptoms worsened and VEP abnormalities developed patients consistently described hallucinatory dysperceptions of the virtual environment. The two studies therefore show that VH can occur in two seemingly distinct conditions, one is related to chronic treatment and to a sleep disorder frequently observed in PD, the other is probably related to a hypodopaminergic state. Our studies support a recently proposed integrative model of VH, and show that the neural circuits purported to explain VH must include the retinal dopaminergic system and the REM sleep regulatory system.

Antiparkinson Agents↗

The N-terminal 12 residue long peptide of HIV gp41 is the minimal peptide sufficient to induce significant T-cell-like membrane destabilization in vitro.

Here, we predicted the minimal N-terminal fragment of gp41 required to induce significant membrane destabilization using IMPALA. This algorithm is dedicated to predict peptide interaction with a membrane. We based our prediction of the minimal fusion peptide on the tilted peptide theory. This theory proposes that some protein fragments having a peculiar distribution of hydrophobicity adopt a tilted orientation at a hydrophobic/hydrophilic interface. As a result of this orientation, tilted peptides should disrupt the interface. We analysed in silico the membrane-interacting properties of gp41 N-terminal peptides of different length derived from the isolate BRU and from an alignment of 710 HIV strains available on the Los Alamos National Laboratory. Molecular modelling results indicated that the 12 residue long peptide should be the minimal fusion peptide. We then assayed lipid-mixing and leakage of T-cell-like liposomes with N-terminal peptides of different length as first challenge of our predictions. Experimental results confirmed that the 12 residue long peptide is necessary and sufficient to induce membrane destabilization to the same extent as the 23 residue long fusion peptide. In silico analysis of some fusion-incompetent mutants presented in the literature further revealed that they cannot insert into a modelled membrane correctly tilted. According to this work, the tilted peptide model appears to explain at least partly the membrane destabilization properties of HIV fusion peptide.

Algorithms↗

Lipid-destabilising properties of a peptide with structural plasticity.

The Chameleon peptide (Cham) is a peptide designed from two regions of the GB1 protein, one folded as an alpha-helix and the other as a beta structure. Depending on the environment, the Cham peptide adopts an alpha or a beta conformation when inserted in different locations of GB1. This environment dependence is also observed for tilted peptides. These short protein fragments, able to destabilise organised system, are mainly folded in beta structure in water and in alpha helix in a hydrophobic environment, like the lipid bilayer. In this paper, we tested whether the Cham peptide can be qualified as a tilted peptide. For this, we have compared the properties of Cham peptide (hydrophobicity, destabilising properties, conformation) to those of tilted peptides. The results suggest that Cham is a tilted peptide. Our study, together the presence of tilted fragments in transconformational proteins, suggests a relationship between tilted peptides and structural lability.

Hydrophobic and Hydrophilic Interactions↗

Low maternal vitamin B12 status is associated with intrauterine growth retardation in urban South Indians.

OBJECTIVE: To assess the maternal sociodemographic, anthropometric, dietary and micronutrient status in apparently healthy pregnant women in order to determine their associations with intrauterine growth retardation (IUGR). DESIGN: Prospective observational study. SETTING: Bangalore City, India. SUBJECTS: A total of 478 women were recruited at 12.9+/-3.3 weeks of gestation and followed up at the first, second and third trimesters of pregnancy and at delivery. The dropout rate was 8.5%. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Birth weight was measured at hospital delivery. RESULTS: The mean birth weight was 2.85+/-0.45 kg. In all, 28.6% of newborns were IUGR. There was a strong inverse relationship between maternal educational level and risk of IUGR. A low body weight at baseline was also associated with a high risk of IUGR. Compared with women in the highest quartile for second trimester weight gain, those in the lowest quartile had a significantly higher adjusted odds ratio (AOR: 3.98; 95% CI: 1.83, 8.65) for IUGR. Women in the lowest tertile for serum vitamin B(12) concentration during each of the three trimesters of pregnancy had significantly higher risk of IUGR (AOR: 5.98, 9.28 and 2.81 for trimesters 1-3, respectively). CONCLUSIONS: The present study demonstrates associations between educational status, maternal weight and gestational weight gain with IUGR. Importantly, in a subsample, there were strong associations of vitamin B(12) status with IUGR, suggesting that better socioeconomic conditions, improved nutritional status and early detection of vitamin B(12) deficiency in pregnancy combined with appropriate interventions are likely to play an important role in reducing IUGR.

Adolescent↗

Real-time elastography--an advanced method of ultrasound: First results in 108 patients with breast lesions.

OBJECTIVES: To evaluate whether real-time elastography, a new, non-invasive method for the diagnosis of breast cancer, improves the differentiation and characterization of benign and malignant breast lesions. METHODS: Real-time elastography was carried out in 108 potential breast tumor patients with cytologically or histologically confirmed focal breast lesions (59 benign, 49 malignant; median age, 53.9 years; range, 16-84 years). Tumor and healthy tissue were differentiated by measurement of elasticity based on the correlation between tissue properties and elasticity modulus. Evaluation was performed using the three-dimensional (3D) finite element method, in which the information is color-coded and superimposed on the B-mode ultrasound image. A second observer evaluated the elastography images, in order to improve the objectivity of the method. The results of B-mode scan and elastography were compared with those of histology and previous sonographic findings. Sensitivities and specificities were calculated, taking histology as the gold standard. RESULTS: B-mode ultrasound had a sensitivity of 91.8% and a specificity of 78%, compared with sensitivities of 77.6% and 79.6% and specificities of 91.5% and 84.7%, respectively, for the two observers evaluating elastography. Agreement between B-mode ultrasound and elastography was good, yielding a weighted kappa of 0.67. CONCLUSIONS: Our initial clinical results suggest that real-time elastography improves the specificity of breast lesion diagnosis and is a promising new approach for the diagnosis of breast cancer. Elastography provides additional information for differentiating malignant BI-RADS (breast imaging reporting and data system) category IV lesions.

Adolescent↗

Magnesium restores altered aquaporin-4 immunoreactivity following traumatic brain injury to a pre-injury state.

Magnesium reduces edema following traumatic brain injury (TBI), although the associated mechanisms are unknown. Recent studies suggest that edema formation after TBI may be related to alterations in aquaporin-4 (AQP4) channels. In this study, we characterize the effects of magnesium administration on AQP4 immunoreactivity following TBI. Male Sprague-Dawley rats were injured by impact-acceleration diffuse TBI and a subgroup was administered 30 mg/kg magnesium sulphate 30 minutes after injury. Animals were fixed by perfusion 5 hours later, which corresponded to the time of maximum edema formation according to previous studies. One half of the brain was cut using a Vibratome and the other half blocked in paraffin wax. Wax and Vibratome sections were immunostained for detection of AQP4 by light and electron microscopy, respectively. In untreated animals, AQP4 immunoreactivity was increased in the subependymal inner glia limitans and the subpial outer glia limitans, and decreased in perivascular astrocytic processes in the cerebrum and brain stem. In contrast, animals treated with magnesium sulphate had AQP4 profiles similar to normal and sham control animals. We conclude that magnesium decreases brain edema formation after TBI, possibly by restoring the polarized state of astrocytes and by down-regulation of AQP4 channels in astrocytes.

Animals↗

[A new method for standardized diagnosis following renal transplantation. Ultrasound with contrast enhancement].

Ultrasound (US) imaging is an important diagnostic tool following renal transplantation. Unfortunately, due to the heterogeneity of the recipients and their multimorbidity, imaging procedures in the early phase after kidney transplantation are difficult and of limited use. We performed a study to evaluate the use of a contrast enhancer for US examination as a standardized method in the follow-up of kidney transplant recipients.The study included 40 recipients: 32 were examined on the 5th to 7th day following transplantation and 8 patients at the time when clinically suspicious findings occurred (acute rejection, tumor, acute tubular necrosis). Following the intravenous application of the contrast medium, pictures were taken during the arterial and parenchymatous phase and compared with conventional B-mode and power Doppler pictures of the same visual plane. Three examiners assessed different parameters of the transplant organ (max. vascularized area, suspected hematomas, tumors, rejection, acute tubular necrosis). Findings were confirmed by histological results of a biopsy if rejection, tumor, or acute tubular necrosis were suspected. Application of ultrasound contrast medium significantly increased visualization of the vascularized kidney area. Also, US findings in the follow-up after acute rejection therapy corresponded with the clinical course; 19 hematomas could be detected with contrast medium compared to only 9 without. With contrast medium a perfusion deficit was detectable in three patients compared to one patient with power Doppler US. Also, US contrast medium helped to detect tumor vascularization in two patients in whom conventional sonography suspected no abnormality. Ultrasound contrast medium enhancement is a reproducible, reliable, and easy to apply method which is superior to conventional sonography in the follow-up after kidney transplantation. This method is also helpful to detect and control acute rejections and to better visualize hematomas, deficits of perfusion, and tumors.

Adolescent↗

Anthropometry and body composition of south Indian babies at birth.

OBJECTIVES: To assess the consequences on body composition of increasing birth weight in Indian babies in relation to reported values in Western babies, and to assess the relationship between maternal and neonatal anthropometry and body composition. DESIGN: Prospective observational study. SETTING: Bangalore City, India. SUBJECTS: A total of 712 women were recruited at 12.5+/-3.1 weeks of gestation (mean+/-standard deviation, SD) and followed up until delivery; 14.5% were lost to follow-up. Maternal body weight, height, mid upper-arm circumference and skinfold thicknesses were measured at recruitment. Weight and body composition of the baby (skinfold thicknesses, mid upper-arm circumference, derived arm fat index and arm muscle index; AFI and AMI, respectively) were measured at birth in hospital. RESULTS: The mean+/-SD birth weight of all newborns was 2.80+/-0.44 kg. Birth weight was significantly related to the triceps and subscapular skinfold thickness of the baby. In a small number of babies with large birth weight for gestational age, there was a relatively higher normalised AFI relative to AMI than for babies with lower or appropriate birth weight for gestational age. Maternal height and fat-free mass were significantly associated with the baby's length at birth. CONCLUSIONS: Skinfold thicknesses in Indian babies were similar to those reported in a Western population with comparable birth weights, and the relationship of AFI to birth weight appeared to be steeper in Indian babies. Thus, measures to increase birth weight in Indian babies should take into account possible adverse consequences on body composition. There were no significant relationships between maternal anthropometry and body composition at birth on multivariate analysis, except for sum of the baby's skinfold thicknesses and maternal fat-free mass (P<0.02).

Adolescent↗

[Signal loss in magnetic resonance imaging caused by intraoral anchored dental magnetic materials].

PURPOSE: To measure the maximum extent of the signal loss areas in the center of the susceptibility artifacts generated by ferromagnetic dental magnet attachments using three different sequences in the 1.5 and 3.0 Tesla MRI. MATERIALS AND METHODS: Five different pieces of standard dental magnet attachments with volumes of 6.5 to 31.4 mm(3) were used: a NdFeB magnet with an open magnetic field, a NdFeB magnet with a closed magnetic field, a SmCo magnet with an open magnetic field, a stainless steel keeper (AUM-20) and a PdCo piece. The attachments were placed between two cylindrical phantoms and examined in 1.5 and 3.0 Tesla MRI using gradient echo and T1- and T2-weighted spin echoes. We measured the maximum extent of the generated signal loss areas parallel and perpendicular to the direction of B (O). RESULTS: In gradient echoes the artifacts were substantially larger and symmetrically adjusted around the object. The areas with total signal loss were mushroom-like with a maximum extent of 7.4 to 9.7 cm parallel to the direction of B (O) and 6.7 to 7.4 cm perpendicular to B (O). In spin echoes the signal loss areas were obviously smaller, but not centered. The maximum values ranged between 4.9 and 7.2 cm (parallel B (O)) and 3.6 and 7.0 cm (perpendicular B (O)). The different ferromagnetic attachments had no clinically relevant influence on the signal loss neither in 1.5 T nor 3.0 T MRI. CONCLUSIONS: Ferromagnetic materials used in dentistry are not intraorally standardized. To ensure, that the area of interest is not affected by the described artifacts, the maximum extent of the signal loss area should be assumed: a radius of up to 7 cm in 1.5 and 3.0 T MRI by T1 and T2 sequences, and a radius of up to 10 cm in T2* sequences. To decide whether magnet attachments have to be removed before MR imaging, physicians should consider both the intact retention of the keepers and the safety distance between the ferromagnetic objects and the area of interest.

Artifacts↗

[Characterization of sonographically detected breast lesions using three-dimensional data sets].

PURPOSE: The diagnostic value of 3D ultrasound (US) was evaluated in comparison to 2D US on the basis of a set of pre-defined criteria for breast lesions. The individual criteria were correlated with the histological findings and they were ranked according to their significance for lesion characterization in both 3D US and 2D US. MATERIALS AND METHODS: A total of 92 breast lesions were examined of which 61 were malignant and 31 were benign, as confirmed by histology of core biopsy specimens (Aplio 80, Toshiba, Otawara, Japan). The 2D and 3D data sets were stored digitally. The vascular tree was stored separately using 3D fusion. In addition, a power Doppler (PD) examination was performed. A total of 644 individual images were evaluated by two independent readers. The lesions were evaluated using established criteria (BI-RADS classification). For statistical evaluation, the individual US measurements were classified according to the following two groups: those suggesting malignant lesions and those suggestive of benign lesions. Pearsons's chi-square test was performed for both groups. The 2D and 3D techniques were compared directly using kappa (kappa) statistics. Odds ratios (OR) were determined for the purpose of weighting the individual criteria. The sensitivities and specificities of 2D and 3D US were calculated. RESULTS: The diagnostic value of 3D US was comparable to that of 2D US, with only slight differences observed for specific measurements. Analysis of 2D US data indicated that there was a strong correlation between malignant tumor growth and two specific 2D criteria: lesion margin and effect of the lesion on adjacent breast tissue (r (2) = 0.632, p < 0.001). Analysis of 3D images indicated that the significant measurements for tumor malignancy were shape and lesion margin in sagittal, transverse (r (2) = 0741, p < 0.001), and frontal views (r (2) = 0.592, p < 0.001) as well as retraction and lesion demarcation in the frontal views (r (2) = 0.649, p < 0.001). The comparison of 2D and 3D yielded primarily moderate (kappa = 0.412) to good (kappa = 0.789) agreement between the individual criteria. Crucial criteria for lesion characterization were the effect of the lesion on adjacent breast tissue (OR 47.8 [16.0-143.3]) in 2D US and the lesion margin (OR 36.4 [15.3-86.6]) and the 3 additional criteria of the frontal plane (OR 21.9-32.9) in 3D US. The two US techniques had comparable sensitivities (2D/3D 95-97 %/92-95 %) and specificities (2D/3D 54-58 %/61-67 %). The reconstructed 3D view of the vascular tree was subjectively considered to be helpful by both readers. A higher degree of vascularization was observed with 3D US. CONCLUSIONS: The diagnostic role of 3D ultrasound in the diagnostic evaluation of breast cancer is comparable to that of 2D US. Our findings illustrate the significance of the evaluation of frontal views in lesion characterization.

Adult↗