MR spectroscopy study of dichloroacetate treatment after ischemic stroke.

In a double-blind, placebo-controlled study, we used 1H MR spectroscopy to assess the effect of a single infusion of sodium dichloroacetate on lesion lactate 1 to 5 days after ischemic stroke. Apparent trends toward a reduction in lactate/N-acetyl compound ratios were seen at the higher drug doses employed, and in patients treated in the first 2 days following infarction. Use of spectroscopic measures as endpoints is feasible in acute stroke clinical trials.

A potential role for p15(Ink4b) and p57(Kip2) in liver development.

Hepatocytes undergo marked changes in proliferation during normal liver development. In order to elucidate the mechanism for these changes, we examined the ontogeny of expression for the known cyclin-dependent kinase inhibitors (CKIs), p15(Ink4b), p16(Ink4a), p18(Ink4c), p19(Ink4d), p21(Cip1), p27(Kip1) and p57(Kip2). All except p16(Ink4a) were expressed at some time between late gestation and adulthood. The mRNA and protein expression patterns for p15(Ink4b) and p57(Kip2) were consistent with a role for these CKIs in the regulation of hepatocyte proliferation. Specifically, p57(Kip2) may contribute to hepatocyte growth arrest that occurs in term fetuses, while p15(Ink4b) may contribute to the maintenance of adult hepatocytes in a quiescent state. These results assign a possible role to two CKIs not previously identified as involved in hepatocyte cell cycle control.

Magnetic source imaging and brain surgery: presurgical and intraoperative planning in 26 patients.

OBJECT: The availability of large-array biomagnetometers has led to advances in magnetoencephalography that permit scientists and clinicians to map selected brain functions onto magnetic resonance images. This merging of technologies is termed magnetic source (MS) imaging. The present study was undertaken to assess the role of MS imaging for the guidance of presurgical planning and intraoperative neurosurgical technique used in patients with intracranial mass lesions. METHODS: Twenty-six patients with intracranial mass lesions underwent a medical evaluation consisting of MS imaging, a clinical history, a neurological examination, and assessment with the Karnofsky Performance Scale. Magnetic source imaging was used to locate the somatosensory cortex in 25 patients, the visual cortex in six, and the auditory cortex in four. The distance between the lesion and the functional cortex was determined for each patient. Twenty-one patients underwent a neurosurgical procedure. As a surgical adjunct, a frameless stereotactic navigational system was used in 17 cases and a standard stereotactic apparatus in four cases. Because of the results of their MS imaging examination, two patients were not offered surgery, four underwent a stereotactic biopsy procedure, 10 were treated with a subtotal surgical resection, and seven were treated with complete surgical resection. One patient deteriorated before a procedure could be scheduled and, therefore, was not offered surgery, and two patients were offered surgery but declined. Three patients experienced surgery-related complications. CONCLUSIONS: Magnetic source imaging is an important noninvasive neurodiagnostic tool that provides critical information regarding the spatial relationship of a brain lesion to functional cortex. By providing this information, MS imaging facilitates a minimum-risk management strategy and helps guide operative neurosurgical technique in patients with intracranial mass lesions.

MRI morphometry of mamillary bodies, caudate nuclei, and prefrontal cortices after chemotherapy for childhood leukemia: multivariate models of early and late developing memory subsystems.

Neurotoxic intrathecal chemotherapy for childhood acute lymphoblastic leukemia (ALL) affects developing structures and functions of memory and learning subsystems selectively. Results show significant reductions in magnetic resonance imaging morphometry of mamillary bodies, components of the corticolimbic-diencephalic subsystem subserving functionally later developing, single-trial memory, nonsignificant changes in bilateral heads of the caudate nuclei, components of the corticostriatal subsystem subserving functionally earlier developing, multitrial learning, significant reductions in prefrontal cortical volume, visual and verbal single-trial memory deficits, and visuospatial, but not verbal, multitrial learning deficits. Multiple regression models provide evidence for partial dissociation and connectivity between the subsystems, and suggest that greater involvement of caudate may compensate for inefficient corticolimbic-diencephalic components.

Effect of head-down tilt on brain water distribution.

Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T2 magnetic resonance imaging. We obtained T2 images of sagittal slices from five subjects while they were supine and during -13 degrees HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.

Evidence for cerebellar-frontal subsystem changes in children treated with intrathecal chemotherapy for leukemia: enhanced data analysis using an effect size model.

BACKGROUND: Following brain insult in early childhood, the later maturing neocerebellum and frontal lobes frequently show abnormalities. OBJECTIVE: To investigate the morphologic characteristics and function of a proposed cerebellar-frontal subsystem in children treated for acute lymphoblastic leukemia (ALL) with intrathecal methotrexate using quantitative magnetic resonance imaging, neuropsychological measures, nonlinear multiple regression analysis, and a statistical effect size model that augments interpretive validity of nonsignificant statistical findings, particularly from small sample size studies. DESIGN: Comparison and relationship of magnetic resonance imaging morphometry of cerebellar lobuli I-V and VI-VII and prefrontal cortices, and performance on 5 neuropsychological tests assessing visual-spatial attention, short-term memory, and visuomotor organization and coordination between childhood survivors of ALL and a matched control group. PARTICIPANTS: Ten childhood survivors of ALL treated between 1982 and 1989 with standard 3-year intrathecal chemotherapy, and matched control subjects. MAIN OUTCOME MEASURES: Morphometric results of cerebellar lobuli I-V and VI-VII and prefrontal cortices, and results of Trail-Making Tests, Rey-Osterreith Complex Figure Test, WISC-III Coding. RESULTS: Significant effect size model values for outcome measures in the ALL group support deficits in lobuli VI-VII and prefrontal cortices, and neuropsychological performance. Multiple regression analysis results were consistent with hypothesized involvement of a cerebellar-frontal brain subsystem. CONCLUSION: Treatment of children with ALL with intrathecal methotrexate before 5 years of age has structural and functional effects on the developing neocerebellar-frontal subsystem.

Low birth weight in urban Harare.

OBJECTIVES: 1. To measure the incidence of low birth weight from all institutional deliveries in a defined catchment area of urban Harare. 2. To estimate the relative proportions of preterm and small for gestational age (SGA). DESIGN: The study was descriptive and was conducted during the last three months of 1986. SETTING: The low risk maternity units in three high density suburbs, Highfield, Glen Norah and Glen View and the referral centre Harare Central Hospital. SUBJECTS: All babies born to women residing in the study areas in the maternity clinics and those transferred to the referral hospital were identified and weighed. MAIN OUTCOME MEASURES: For low birthweight babies gestation was estimated by the Dubowitz method and perinatal outcome was recorded. RESULTS: During the three month study period in 1986, 2,056 babies in total were born; 223 (10.8%) of which were low birthweight. Of these 65 (44%) were preterm and 55 (37%) were SGA. CONCLUSION: The findings show a lower percentage of low birthweight and SGA babies than in many developing countries but higher than the norm for developed countries. The study demonstrates a need for resources to prevent low birthweight delivery and improve care for low birthweight babies.

PIP: A 1986 descriptive study of all institutional deliveries in a defined catchment area of urban Harare, Zimbabwe, investigated the incidence of low birth weight (LBW, under 2500 grams), and the relative contributions of preterm and small-for-gestational-age (SGA, gestational age 37 weeks or above plus LBW) deliveries to LBW. Since most LBW statistics are based on deliveries from central hospitals that serve as referral centers for distant rural areas, they cannot be considered representative of a particular urban population. The high-density, low-income Harare suburbs of Highfield, Glen Norah, and Glen View were selected for the analysis. During the 3-month study period, there were 2056 registered births in the 3 communities. 1101 of these deliveries occurred at the 3 low-risk maternal clinics serving these areas and 955 took place, after referral, at the high-risk Harare Central Hospital. There were 223 LBW infants (10.8%), 50 of whom were delivered in the clinics and 173 in the referral hospital. All 17 infants weighing under 1000 grams were delivered at the hospital. 148 LBW infants (including 13 stillbirths, 6 early neonatal deaths, and 14 sets of twins) were selected for further study. 44% of these infants were preterm and 37% were SGA; the remainder were appropriate for gestational age. When the data were adjusted to conform with the Villa/Belizan categories, 5.3% were LBW/preterm and 5.5% were LBW/intrauterine growth retardation. Overall, the LBW pattern identified in this study falls between that of a developed and a developing country, which is presumably reflective of the high level of general development in Harare.

Proton magnetic resonance spectroscopy in patients with glial tumors: a multicenter study.

The authors represent a cooperative group of 15 institutions that examined the feasibility of using metabolic features observed in vivo with 1H-magnetic resonance (MR) spectroscopy to characterize brain tumors of the glial type. The institutions provided blinded, centralized MR spectroscopy data processing long with independent central review of MR spectroscopy voxel placement, composition and contamination by brain, histopathological typing using current World Health Organization criteria, and clinical data. Proton 1H-MR spectroscopy was performed using a spin-echo technique to obtain spectra from 8-cc voxels in the tumor and when feasible in the contralateral brain. Eighty-six cases were assessable, 41 of which had contralateral brain spectra. Glial tumors had significantly elevated intensities of choline signals, decreased intensities of creatine signals, and decreased intensities of N-acetylaspartate compared to brain. Choline signal intensities were highest in astrocytomas and anaplastic astrocytomas, and creatine signal intensities were lowest in glioblastomas. However, whether expressed relative to brain or as intratumoral ratios, these metabolic characteristics exhibited large variations within each subtype of glial tumor. The resulting overlaps precluded diagnostic accuracy in the distinction of low-and high-grade tumors. Although the extent of contamination of the 1H-MR spectroscopy voxel by brain had a marked effect on metabolite concentrations and ratios, selection of cases with minimal contamination did not reduce these overlaps. Thus, each type and grade of tumor is a metabolically hetero-geneous group. Lactate occurred infrequently and in all grades. Mobile lipids, on the other hand, occurred in 41% of high-grade tumors with higher mean amounts found in glioblastomas. This result, coupled with the recent demonstration that intratumoral mobile lipids correlate with microscopic tumor cell necrosis, leads to the hypothesis that mobile lipids observed in vivo in 1H-MR spectroscopy may correlate independently with prognosis of individual patients.

Comparison of primary motor cortex localization using functional magnetic resonance imaging and magnetoencephalography.

The primary goal of the study was to compare estimates of motor cortex localization from functional magnetic resonance imaging (FMRI) and magnetoencephalography (MEG). Thirteen normal volunteers were studied using both methods. FMRI was performed on a clinical 1.5 T system using gradient-echo acquisitions and basic t-test processing. MEG primary motor field was characterized by a single dipole model. Comparisons between the location of the best-fitting MEG dipole and the FMRI activation results were made using both fixed regions-of-interest weighted averaging and clustering analysis to reduce the observed FMRI activations to a single representative location. Both FMRI and MEG identified expected anatomic regions of primary motor activity and there was overall agreement to within 10 mm between these two functional imaging modalities. Given the observed agreement between these two techniques, it does not appear that the proposed artifactual mechanisms of local bulk motions or large-vessel sensitivity will seriously preclude the clinical utility of FMRI for preoperative localization of sensorimotor cortex.

Haemolytic uraemic syndrome following Shigella dysenteriae type 1 outbreak in Zimbabwe: a clinical experience.

Shigella dysenteriae type 1 related dysentery outbreak in Zimbabwe at the end of 1992 has been associated with an increase in the frequency of haemolytic uraemic syndrome (HUS). In order to document this new clinical experience a retrospective study was undertaken to document clinical and laboratory features, treatment and outcome of children with HUS. During the period January 1993 to June 1994, 96 children with HUS were seen at the referral hospitals in Harare. Severe and prolonged anaemia was a common feature and 80 pc of the children were given blood transfusions. Severe anaemia (HB < 6g/dl) was however, present in 50 pc of the children prior to death. Leucocytosis (white blood cell count > 20 x 10(9)/L) was present in 87 pc of the children on admission and there was no association between the level of leucocytosis and anuria. Anuria was present in 37 (39 pc) and was associated with a mortality of 68 pc. Peritoneal dialysis was performed in 26 (27 pc) patients. Major neurological complications were seen in a third of the children. Thirty eight children died, an overall case fatality rate (CFR) of 40 pc. Earlier recognition, prompt and comprehensive supportive therapy may improve the immediate survival in children with HUS in Zimbabwe.

Mapping function in the human brain with magnetoencephalography, anatomical magnetic resonance imaging, and functional magnetic resonance imaging.

Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuro-imaging methods.

1H MR spectroscopy in patients with metastatic brain tumors: a multicenter study.

In a cooperative study involving six clinical MR centers, localized 1H MR spectroscopy was used to characterize untreated metastatic brain tumors (40 cases, 45 lesions). Cubic volumes (3.4 or 8 cm3) filled for more than 50% by metastatic brain tissue were examined by single-voxel double spin echo MRS, by using chemical shift selective imaging (CHESS) pulses for water suppression and TE = 135 ms. Choline (Cho), creatine (Cr) and N-acetyl aspartate (NAA) levels in brain metastases of mammary carcinoma (n = 13), lung cancer (n = 11) and melanoma (n = 10) were similar. Metastasis NAA/Cho signal intensity ratio varied between 0.00 and 1.17, compared with 2.68 +/- 0.56 (SD) in lobus occipitalis and 1.94 +/- 0.63 in corpus nuclei caudati region (P < 0.0001, both). 1H MR spectroscopy, although not suited to recognize the primary tumor of metastases, could serve as a clinical test for excluding (metastatic) tumor as cause of solitary focal brain disorders that are hard to diagnose with current imaging methods.

Neuromagnetic mapping of brain function.

Magnetic source imaging, a technique that combines magnetoencephalography (MEG) and magnetic resonance (MR) imaging, was used to localize the somatosensory and auditory cortex in seven healthy subjects. Functional neuromagnetic data were obtained with a 37-channel biomagnetometer. Structural MR imaging data were obtained with a 1.5-T superconducting imager. Coordinates used in defining MEG and MR imaging space were reconciled to produce magnetic source images that displayed the putative locations of somatosensory and auditory activity in relation to brain anatomy. Sources of somatosensory activity were typically localized to the postcentral gyrus; sources of auditory activity were localized to the superior temporal plane. Extension of these results to patients with tumors (or other disorders) that distort normal brain anatomy has the potential to make noninvasive magnetic source imaging examinations clinically useful in guiding neurosurgical interventional procedures.

Noninvasive preoperative cortical localization by magnetic source imaging.

The authors successfully used magnetoencephalography and MR data to localize the sensorimotor cortex in two patients prior to neurosurgery; preoperative localization influenced surgical management.

Purification, immunochemical characterization, and immunohistochemical localization of rat hepatic aryl sulfotransferase IV.

Aryl sulfotransferases catalyze the formation of sulfuric acid esters from a diverse group of endogenous and xenobiotic organic chemicals. The isoenzyme of aryl sulfotransferase in livers of male Sprague-Dawley rats that exhibits the most varied substrate specificity is aryl sulfotransferase IV. A new method for the purification to homogeneity of aryl sulfotransferase IV was developed that, when compared with previously described procedures, provided a greater than 10-fold increase in total yield of enzyme/g of tissue. Homogeneous aryl sulfotransferase IV was used to prepare polyclonal antibodies in male New Zealand White rabbits. Results of immunochemical analyses demonstrated that these antibodies reacted with only a single protein in rat hepatic 100,000 x g supernatant fractions and, further, that the immunoreactive protein had the isoelectric point and subunit molecular mass characteristic of aryl sulfotransferase IV. Immunohistochemical analyses demonstrated that aryl sulfotransferase IV is present in hepatocytes throughout the liver, although centrilobular cells contain a significantly greater (p less than 0.01) amount of aryl sulfotransferase IV than do either midzonal or periportal cells, in which similar levels of the enzyme are found.

Differentiation of adolescent activity participation.

The sex typing or lack of it among 133 adolescent activities was investigated. Twenty-seven percent (32) of the activities on an Adolescent Activity Questionnaire showed very clear participation differences for male and female adolescents (11 to 18 years old). The initial two factors extracted in a principal components factor analysis were easily interpreted as feminine and masculine activities. Discriminant function analysis of 15 items from the first three factors yielded an 8-item function on the basis of which every sample member was correctly classified as male or female. Masculine activities included more sports-related activities and activities dealing with mechanics and building, whereas feminine activities were domestic in nature and included more sedentary activities (e.g., reading, writing in diaries).

Klebsiella pneumoniae osteomyelitis: demonstration by three-phase radionuclide bone imaging.

The Klebsiella pneumoniae bacillus is a rare cause of acute hematogenous osteomyelitis of long bones. Bony involvement usually develops from a bacteremia associated with a Klebsiella pulmonary or urinary tract infection. Diabetes mellitus, alcoholism, or cirrhosis are predisposing conditions to the development of this form of osteomyelitis. A case report follows in which two sites of Klebsiella osteomyelitis were demonstrated by three-phase bone imaging in a patient with both diabetes and alcoholism.