Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort.

Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. Participants were drawn from the Drakenstein Child Health Study (DCHS), an ongoing birth cohort study conducted in a peri-urban community in the Western Cape, South Africa. A total of 342 scans acquired from 237 children as neonates (N = 82 scans: 30 PAE; 52 controls) and at ages 2-3 (N = 121 scans: 27 PAE; 94 controls) and 6-7 years (N = 139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28 to 32 weeks' gestation. Linear mixed effects models with restricted maxium likelihood to accommodate missing data were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p = 0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p = 0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2-3 years of age, followed by a more tapered trajectory for the period from 2-3 to 6-7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.

Improved Myelination following Camp Leg Power, a Selective Motor Control Intervention for Children with Spastic Bilateral Cerebral Palsy: A Diffusion Tensor MRI Study.

BACKGROUND AND PURPOSE: Children with spastic cerebral palsy have motor deficits associated with periventricular leukomalacia indicating WM damage to the corticospinal tracts. We investigated whether practice of skilled lower extremity selective motor control movements would elicit neuroplasticity. MATERIALS AND METHODS: Twelve children with spastic bilateral cerebral palsy and periventricular leukomalacia born preterm (mean age, 11.5 years; age range, 7.3-16.6 years) participated in a lower extremity selective motor control intervention, Camp Leg Power. Activities promoted isolated joint movement including isokinetic knee exercises, ankle-controlled gaming, gait training, and sensorimotor activities (3 hours/day, 15 sessions, 1 month). DWI scans were collected pre- and postintervention. Tract-Based Spatial Statistics was used to analyze changes in fractional anisotropy, radial diffusivity, axial diffusivity, and mean diffusivity. RESULTS: Significantly reduced radial diffusivity (P < . 05) was found within corticospinal tract ROIs, including 28.4% of the left and 3.6% of the right posterior limb of the internal capsule and 14.1% of the left superior corona radiata. Reduced mean diffusivity was found within the same ROIs (13.3%, 11.6%, and 6.6%, respectively). Additionally, decreased radial diffusivity was observed in the left primary motor cortex. Additional WM tracts had decreased radial diffusivity and mean diffusivity, including the anterior limb of the internal capsule, external capsule, anterior corona radiata, and corpus callosum body and genu. CONCLUSIONS: Myelination of the corticospinal tracts improved following Camp Leg Power. Neighboring WM changes suggest recruitment of additional tracts involved in regulating neuroplasticity of the motor regions. Intensive practice of skilled lower extremity selective motor control movements promotes neuroplasticity in children with spastic bilateral cerebral palsy.

Nonparametric Bayesian Regression and Classification on Manifolds, With Applications to 3D Cochlear Shapes.

Advanced shape analysis studies such as regression and classification need to be performed on curved manifolds, where often, there is a lack of standard statistical formulations. To overcome these limitations, we introduce a novel machine-learning method on the shape space of curves that avoids direct inference on infinite-dimensional spaces and instead performs Bayesian inference with spherical Gaussian processes decomposition. As an application, we study the shape of the cochlear spiral-shaped cavity within the petrous part of the temporal bone. This problem is particularly challenging due to the relationship between shape and gender, especially in children. Experimental results for both synthetic and real data show improved performance compared to state-of-the-art methods.

Selective Motor Control is a Clinical Correlate of Brain Motor Tract Impairment in Children with Spastic Bilateral Cerebral Palsy.

BACKGROUND AND PURPOSE: Selective voluntary motor control is an important factor influencing gross motor function, interjoint coordination, and the outcome of hamstring-lengthening surgery in spastic cerebral palsy. Using DTI, we investigated whether selective voluntary motor control would show strong correlations with WM motor tract microstructure and whether selective voluntary motor control is more sensitive to global WM impairment than gross motor function. MATERIALS AND METHODS: Children with spastic bilateral cerebral palsy born preterm and typically developing children were recruited. The Selective Control Assessment of the Lower Extremity (SCALE) and Gross Motor Function Measure (GMFM) were assessed in participants with cerebral palsy. Participants underwent brain MR imaging to collect DWI data. Tract-Based Spatial Statistics was used to analyze the WM for between-group differences and correlations with SCALE and GMFM. ROI analyses compared motor regions. RESULTS: Twelve children with cerebral palsy (mean age, 11.5 years) and 12 typically developing children (mean age, 10.3 years) participated. Altered DTI outcomes were found throughout the whole brain for the cerebral palsy group. SCALE, developed to evaluate selective voluntary motor control in cerebral palsy, showed significant positive correlations with fractional anisotropy in more WM voxels throughout the whole brain and for motor regions, including the corticospinal tract and corpus callosum, compared with GMFM. A significant negative correlation between radial diffusivity and SCALE, but not GMFM, was found within the corpus callosum. CONCLUSIONS: SCALE was a more sensitive clinical correlate of motor and whole-brain WM tract impairment in children with spastic bilateral cerebral palsy, suggesting greater anisotropy and myelination in these regions for those with higher selective voluntary motor control.

Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex.

Electroconvulsive therapy (ECT) is a highly effective and rapidly acting treatment for severe depression. To understand the biological bases of therapeutic response, we examined variations in cortical thickness from magnetic resonance imaging (MRI) data in 29 patients scanned at three time points during an ECT treatment index series and in 29 controls at two time points. Changes in thickness across time and with symptom improvement were evaluated at high spatial resolution across the cortex and within discrete cortical regions of interest. Patients showed increased thickness over the course of ECT in the bilateral anterior cingulate cortex (ACC), inferior and superior temporal, parahippocampal, entorhinal and fusiform cortex and in distributed prefrontal areas. No changes across time occurred in controls. In temporal and fusiform regions showing significant ECT effects, thickness differed between patients and controls at baseline and change in thickness related to therapeutic response in patients. In the ACC, these relationships occurred in treatment responders only, and thickness measured soon after treatment initiation predicted the overall ECT response. ECT leads to widespread neuroplasticity in neocortical, limbic and paralimbic regions and changes relate to the extent of antidepressant response. Variations in ACC thickness, which discriminate treatment responders and predict response early in the course of ECT, may represent a biomarker of overall clinical outcome. Because post-mortem studies show focal reductions in glial density and neuronal size in patients with severe depression, ECT-related increases in thickness may be attributable to neuroplastic processes affecting the size and/or density of neurons and glia and their connections.

Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation.

Statistical shape analysis: clustering, learning, and testing.

Using a differential-geometric treatment of planar shapes, we present tools for: 1) hierarchical clustering of imaged objects according to the shapes of their boundaries, 2) learning of probability models for clusters of shapes, and 3) testing of newly observed shapes under competing probability models. Clustering at any level of hierarchy is performed using a mimimum variance type criterion criterion and a Markov process. Statistical means of clusters provide shapes to be clustered at the next higher level, thus building a hierarchy of shapes. Using finite-dimensional approximations of spaces tangent to the shape space at sample means, we (implicitly) impose probability models on the shape space, and results are illustrated via random sampling and classification (hypothesis testing). Together, hierarchical clustering and hypothesis testing provide an efficient framework for shape retrieval. Examples are presented using shapes and images from ETH, Surrey, and AMCOM databases.

False-positive serological tests in acute malaria.

A range of serological tests, including rapid plasma reagin (RPR), Widal test, enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV)-1 and -2, direct Coombs' test (DCT), and rheumatoid factor (RF) were performed in a well-characterised cohort of 100 patients with acute malaria (Plasmodium vivax infection: 31 patients; P. falciparum infection: 69 patients). Twenty-five healthy volunteers from a similar area were used as controls. Three patients from the severe P. falciparum group died, the remainder of the patients recovered completely. A large proportion of these patients showed false-positive serological reactions during the acute stage of infection, which became negative on re-testing, four weeks after recovery. In tropical countries such as India, where malaria is endemic, results of serological tests should be interpreted with caution in a patient with pyrexia of unknown origin (PUO).

Potential 166Ho radiopharmaceuticals for endovascular radionuclide therapy. II. Preparation and evaluation of 166Ho-DTPA.

166Ho, with its favourable radiation characteristics of t(1/2) 26.8 h and Ebeta 1.85 and 1.75 MeV, is proposed as a suitable choice for the endovascular radionuclide therapy (EVRT) technique of liquid filled, low pressure balloon angioplasty. 166Ho was produced by the (n,gamma) reaction on a natural Ho2O3 target. The specific activity obtained was approximately 100 mCi x mg(-1) when irradiated at a flux of 2 x 10(13) n x cm(-2) s(-1) for approximately 7 days, and the possible contaminant 166Ho(m) was not detected. 166Ho was easily complexed with diethylenetriaminepentaacetic acid (DTPA) at a ligand to metal molar ratio ([L]:[M]) of 1:1 at room temperature (22-23 degrees C) and a reaction time of a few minutes. The radiochemical purity was >99%, as determined by paper chromatography using a mixture of pyridine, ethanol and water (1:2:4) as solvent. The complex had good stability up to 72 h at 37 degrees C in a serum environment. In a study using Swiss mice > 85% of the injected dose was cleared into the urine within 30 min post-injection, with insignificant retention in any major tissues. The studies show that the 166Ho-DTPA complex could be an alternative to the more expensive and difficult to access 188Re based products for EVRT, and provide adequate uniform radiation dose for the arterial vessel wall under treatment.

Preparation of 99mTc-ethylene dicysteine (99mTc-EC) by transchelation using 99mTc-glucoheptonate (99mTc-GHA) and its evaluation for renal function studies.

The complexation of ethylene dicysteine (EC) with 99mTc needs to be carried out at pH 12 to achieve a high radiochemical yield. However, the preparation of the kit at high pH poses difficulties and requires very stringent preparation conditions, as stannous tin, one of the main ingredients in the kit, is unstable at high pH. Hence, an alternative method, involving the transchelation preparation of 99mTc-EC using 99mTc-glucoheptonate (99mTc-GHA) prepared at pH 6.5, was attempted, prompted by the reported success of the preparation of 99mTc-sestamibi (99mTc-MIBI) by this method. The preparation of 99mTc-EC by this method first involved the formation of 99mTc-GHA by the addition of sodium pertechnetate-99mTc to the Sn-GHA kit vial at pH 6.5. 99mTc-EC was formed by the addition of reconstituted EC solution at pH approximately 12 to the preformed 99mTc-GHA. The reaction was allowed to proceed both at room temperature and on a boiling water bath. The pH of the final product was adjusted to pH approximately 7 with 0.5 M phosphate buffer at pH 4-5, without affecting the quality of the product. The urinary excretion of 99mTc-EC prepared by transchelation, tested in mice, was similar to that of directly prepared 99mTc-EC, indicating that the final product prepared by the two methods was the same. The clinical evaluation of the product formulated by the new procedure showed satisfactory findings, comparable with the reports in the literature.

Transfusion transmitted diseases in haemophilics from western India.

BACKGROUND & OBJECTIVES: Transfusion related human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections have been a major cause for morbidity and mortality in the haemophilic population in the west. The prevalence of these markers of transfusion transmitted viral diseases in severe and moderate haemophilia patients was studied. METHODS: The seropositivity for these viral markers was evaluated in 400 haemophilics (323 severe and 77 moderate) in a 5-year survey starting from 1995. First 188 of these patients were also tested for HCV. Serological tests for HIV, HBsAg and HCV were done by third generation ELISA; positive samples were also confirmed by Western blot. RESULTS: Fifteen of the 400 patients were found to be HIV positive (3.8%), 24/400 were HBsAg positive (6%) and 45/188 (23.9%) were positive for HCV (28 for both non-structural and core antigen, 13 for core only and 4 for non-structural antigen only). The lowest age of HIV positivity was 12 yr and that of HCV positivity was 8 yr. INTERPRETATION & CONCLUSION: The above study shows a reduction in blood product related HIV transmission in severe and moderately affected haemophilics but more stringent policy for blood product usage, universal hepatitis C screening, hepatitis B vaccination and continuous awareness programmes for medical staff, general public and patients is needed to reduce the incidence of these diseases in haemophilics.

Preparation and evaluation of samarium (III) phosphate [(153)Sm] colloid (SMPC) for possible therapeutic use.

A simple method of preparation of a new therapeutic colloid, samarium(III) phosphate-(153)Sm (SMPC), is reported involving the reaction of carrier-added (153)SmCl(3) with phosphoric acid. Recovery of the colloid was accomplished by dialysis leading to purification and a radiochemical (RC) yield of more than 90%. The RC purity of purified colloid formulated in isotonic phosphate buffer was more than 99% as assessed by paper chromatography. The product retained its RC purity throughout the period of stability study of 7 days. Complete retention of radioactivity instilled in the rabbit knee joint was observed over the study period of 6 days, with radioactivity in the blood being indistinguishable from the natural background activity. Ninety-six percent of colloidal particles were in the size range of 0.3-2 microm. The promising results demonstrated warrant further studies on SMPC for assessing the suitability for therapy.

Viral infections in newborns through exchange transfusion.

Preprocedure sera of thirty one neonates requiring exchange transfusion were tested for serological markers of HBV, HCV, CMV, HIV and LFT. All the babies were investigated for these parameters one week and two months after transfusion to evaluate the risk of transmission of viral infection. Serological markers for these viral infections were also studied in the mothers and donors' blood to establish the route of infection. Donors' blood used for transfusion was pretested for HBsAg, VDRL and anti-HIV. HBsAg was detected one week post exchange in one baby and two months post exchange in two babies. Exchange transfusion was implicated in two of them, where one donor had HBsAg and the other anti-HBc. Vertical transmission accounted for the remaining one. Out of these HbsAg positive cases, one showed evidence of recently acquired CMV infection. Vertical transmission of anti-HCV was observed in one case. None of the neonates, mothers and donors were positive for anti-HIV. In view of probable serious consequences of HBV and HCV infections, blood used for exchange transfusion ought to be screened for anti-HBc and anti-HCV, besides routine HBsAg, VDRL and anti-HIV screening.

Autoantibodies, immunoglobulins, complement and circulating immune complexes in acute malaria.

BACKGROUND: Malaria caused by Plasmodium vivax and Plasmodium falciparum is common in the Indian subcontinent. Studies conducted elsewhere have suggested that malarial infection causes intense immunostimulation. We screened patients with malarial infection for autoantibodies and measured the immunoglobulin, circulating immune complex and complement levels to determine the extent of immunological alterations in these patients. METHODS: One hundred adults with acute malarial infection confirmed by examination of the peripheral blood smear and 25 age- and sex-matched controls were studied. An autoantibody screen and serum immunoglobulin complement (C3 and C4) and circulating immune complex levels were measured at the time of admission and 4 weeks after they became afebrile. A direct Coomb's test was also done. RESULTS: Anti-ssDNA, anti-dsDNA and rheumatoid factor were positive at the time of admission in 51, 30 and 38 patients respectively. None of the controls were positive for these autoantibodies except for one who was positive for rheumatoid factor. The IgM, IgG and IgA levels were raised in 16, 25 and 36 patients respectively. Circulating immune complex levels were raised in 32 patients and complement C3 and C4 were low in 8 and 31 patients. Follow up studies at 4 weeks in 19 patients showed that the autoantibodies were negative. However, the immunoglobulin, C4 and circulating immune complex levels remained elevated. Six per cent of patients had a positive direct Coomb's test with reticulocytosis at the time of presentation. CONCLUSION: Acute malarial infection can cause false-positive results for anti-ssDNA, anti-dsDNA and rheumatoid factor and may also cause a rise in the serum immunoglobulin, complement and circulating immune complex levels.

A new stain for pollen fertility studies.

The juice from the berries of Cocculus hirsutum was extracted and used for pollen fertility studies in various crops. Two stains were prepared: P.H. Ramanjini (PHR) stain and modified PHR stain. The modified PHR stain contains lactic acid and produces the best staining differentiation. The intensity of the staining was dependent on the thickness of the pollen cell walls, hence PHR stain is recommended for thick walled pollen grains and the modified PHR stain for pollen with relatively thin walls. The preparation of both the stains are very simple, quick and inexpensive.

Ultrasound guided therapeutic catheters: recent developments and clinical results.

The increasing use of intravascular ultrasound technology by clinicians is providing detailed and immediate information about the results of interventions, and this is stimulating the development of new catheters that use ultrasound imaging to control therapy in real time. Cold and thermal balloon angioplasty, atherectomy, embolectomy, laser ablation and rotational recanalization are a few of the interesting capabilities now being added to ultrasound catheters. We report on the development and characteristics of some of these devices and attempt to assess their potential to precisely direct therapy.

Prevalence of HBsAg carriers among some tribes of Madhya Pradesh.

Prevalence of HBsAg was determined in 1314 sera obtained from 11 different tribal populations of five districts of Madhya Pradesh. Reversed passive haemagglutination assay was used for screening showed a HBsAg carrier rate of 2.99 to 21.54 per cent among the various tribes. Significant regional variation was also observed.

Incidence of hepatitis B (Australia) antigen among three communities in malarial Western Maharashtra, India.

The incidence of hepatitis B surface antigen (HBs Ag, Australia antigen) has been determined in three communities residing in an endemic malarial region in Western Maharashtra. A high incidence (5.92%) is found in the Marathas, a socially well-placed community, as compared to Nava-Buddhas (2.62%) and scheduled castes (1.63%) which are socially low-placed communities. A higher incidence (8.91%) among the Maratha females is a surprising observation as the males have been shown to be predominant among HBs Ag carriers in most world populations. A positive association of HBs Ag and the anthropometric traits, skinfold thickness of biceps and triceps, has been observed in the present study. The results demonstrate that other factor(s) (e.g. immunological) besides malarial infection may be involved in the maintenance of a high HBs Ag frequency in Western Maharashtra.