Biomedical subjects
Publications and source records attributed to R J Adams.
We report successful treatment of paroxysmal dystonia (tonic seizures) in three patients with central demyelinating disease (CDD) using acetazolamide alone or in combination with carbamazepine. Acetazolamide is a useful alternative, or an adjunct, to carbamazepine in the treatment of paroxysmal dystonia in CDD.
Several photoreceptoral and neural models have been proposed to account for the development of human vision. To further evaluate those applicable to color vision, the present study examined 40 neonates' (mean age = 3.2 days) chromatic-achromatic discriminations in the mid-spectral region by using an habituation procedure and measures to minimize achromatic cues. Results indicated that newborns showed evidence of discriminating broad-band orange (lambda peak = 595 nm) but not yellow-green (lambda peak = 565 nm) lights from achromatic lights of varying luminance. Collectively, these and previous results imply that although newborns have at least dichromatic color vision, they possess relatively poor chromatic-achromatic discrimination in two spectral regions - in the short-wavelengths (including stimuli of 470-480 nm) and in the mid-wavelengths (including 565 nm). Although several hypotheses were considered, newborns' chromatic 'neutral zones' are best accounted for by models proposing that early color vision is limited by a general inefficiency of preneural (photoreceptoral and optical) mechanisms and/or by a selective immaturity of the SWS cones or the B/Y opponent channel.
Allochiria is the mislocation of sensory stimuli to the corresponding opposite half of the body or space. Obersteiner (1882) introduced the term allochiria (Greek allos = other + chiria = hand), and more than 20 authors employed it in this context over the next 25 years. Stewart (1894) described a related phenomenon in which stimuli are displaced to a different point on the same extremity. He noted that the displacements were different than allochiria and coined the term allachaesthesia (ie, allesthesia) (Greek allaché = elsewhere + aisthésis = perception). Despite this historical background, Jones (1907) redefined both terms in an attempt to increase diagnostic specificity and attributed allochiria to hysteria. Jones' reinterpretation does not appear to be justified historically, etymologically, or scientifically and has resulted in contradictory definitions of allochiria and allesthesia in present-day medical dictionaries and neurologic textbooks. We advocate a return to usage consistent with the original descriptions and word derivations.
Voltage-dependent calcium influx has been shown to regulate the differentiation of cultured amphibian spinal neurons. We have examined the transient elevation of intracellular calcium induced by depolarization, using calcium indicators and confocal microscopy with high temporal and spatial resolution. Rapid calcium elevations in both the nucleus and the cytosol are primarily due to calcium-dependent release of calcium from intracellular stores. Depletion of stores associated with the endoplasmic reticulum reduces all transients. Elevations diminish with neuronal maturation. Depletion of stores of intracellular calcium at early times affects neuronal differentiation in a manner similar to the prevention of influx. The results indicate that both influx and release are necessary to promote neuronal differentiation.
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We have developed a new test which can rapidly evaluate basic color vision in individual infants. The test consists of a series of large cards constructed with Munsell Hues. It uses a modified preferential looking procedure (FPL) and, to control brightness cues, incorporates a two-phase systematic variation of luminance. First, we evaluate an infant's ability to discriminate 9.5 by 16 degrees achromatic patches of varying luminance from a 26 by 65 degrees achromatic background of midrange luminance. In the second phase the test patch is chromatic and its luminance, relative to the background, is varied over a range of about 1.0 log cd/m2. The number of relative luminances chosen for each infant depends upon his/her performance in phase 1. Seventy 2- and 3-month-olds were tested with 4 broad-band chromatic patches, a red (dominant lambda = 660 nm), a yellow (dominant lambda = 580 nm), a green (dominant lambda = 520 nm), and a blue (dominant lambda = 475 nm). Results showed that 3-month-olds had little difficulty making any of the chromatic-achromatic discriminations but many 2-month-olds appeared to fail to discriminate the yellow and green from the background at relative luminances close to an adult brightness match. Most importantly, the test shows promise as a relatively simple, time-efficient, and portable tool for the assessment of early color vision.
Inoculation of simian immunodeficiency virus into cultures of primary rhesus monkey macrophages or CD4-bearing transformed T lymphocytes resulted in persistent infection, with minimal virus replication in the macrophages and extensive replication in the lymphocytes. However, uninfected T cells added to infected macrophages underwent rapid fusion and lysis and were almost completely eliminated without the production of virus particles. Lysis required direct contact between the T cells and the infected macrophages, which enabled binding between CD4 on the former and viral gp120 on the latter to occur. This process was blocked by soluble CD4 and dextran sulphate. Neutralizing antibodies in the serum of an infected macaque prevented cell fusion by preventing infection of the macrophages. However, these antibodies did not prevent fusion when added to previously infected macrophages. Infected macrophages were incorporated into the syncytia of lymphocytes and continued incorporation of new lymphocytes into the syncytia required infected macrophages to be metabolically active. One inference from these studies is that infected macrophages in vivo could help mediate the well known depletion of T4 cells in patients with AIDS.
We undertook a prospective study of consecutive patients to determine the frequency of elevated IgG and IgM anticardiolipin antibodies in transient ischemic attack and ischemic stroke and found elevated IgG antibodies in 8.2% (9 of 110) and IgM in 9.1% (10 of 110), only the former being significantly greater than in a healthy control population. We suggest that anticardiolipin screening be concentrated on the young.
Rhesus progenitor-enriched BM was exposed overnight to SIV and cultured in a limiting dilution assay where the potential for progenitor interaction with lymphocytes or macrophages was low. Virus was consistently isolated late in culture, detection being aided by coculture with CEM174 lymphoblasts. Although infected cells had reduced clonogenic activity, colonies were indistinguishable from those derived from uninfected BM with respect to proliferative potential, morphology, and longevity in culture. Primate immunodeficiency viruses, therefore, may infect immature BM populations, directly affecting hematopoietic activity.
The administration of volatile anesthetics to laboratory animals has been reported to alter brain 5-hydroxytryptamine (serotonin, 5-HT) homeostasis. To examine a potential anesthetic action that could account for these observations, the effect of enflurane on 5-HT accumulation by rat brain synaptosomes was examined. Established techniques were used to prepare synaptosomes and perform uptake assays using [3H]5-hydroxytryptamine as substrate. Exposure of the synaptosomes to enflurane resulted in a concentration-dependent inhibition of serotonin uptake; the apparent I50 was 1.4 +/- 0.3 mM enflurane. Maximum inhibition was observed between enflurane concentrations of 2.6 and 4.3 mM, which inhibited uptake between 62 and 70%. The inhibition was rapid and reversible, and kinetic analysis of the inhibition was consistent with competitive inhibition by enflurane of 5-HT uptake with an apparent KI of 1.61 +/- 0.07 mM. In summary, exposure of synaptosomes to clinically relevant concentrations of enflurane resulted in a rapid, concentration-dependent, and reversible inhibition of 5-HT accumulation. These observations could represent a molecular interaction contributing to the anesthetic properties of enflurane and other volatile anesthetics.
The effects of isoflurane on uptake of 5-hydroxytryptamine(serotonin; 5-HT) by rat brain synaptosomes and binding of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and ketanserin to 5-HT1A and 5-HT2 receptors were examined. Isoflurane caused a concentration-dependent decrease in synaptosomal 5-HT uptake that was kinetically defined as non-competitive; exposure to isoflurane decreased Vmax but had no effect on the apparent Km. Removal of the drug from the reaction mixture resulted in the return of 5-HT accumulation rates to control levels. Isoflurane inhibited 8-OH-DPAT binding to hippocampal membranes by up to 27 +/- 6% at 4.5 mM, but did not significantly affect ketanserin binding to 5-HT2 receptors. These findings suggest that presynaptic actions are more important than postsynaptic actions in the modulation of serotonergic neutrotransmission by isoflurane.
The activity of 5-hydroxytryptamine (serotonin; 5-HT) in the central nervous system modulates sleep, the perception of pain and other functions of the body which might possibly relate to mechanisms of general anesthetic action. While administration of anesthetics has inconsistent effects on the content of 5-HT in brain, in vivo, accumulated data suggest that anesthetic drugs alter 5-HT homeostasis in the central nervous system. In an effort to identify one possible site of anesthetic action, the effect of halothane on the uptake of 5-HT was studied in synaptosomes isolated from the brain of rat. Established techniques were used to prepare the synaptosomal fractions and measure high affinity transport of radiolabelled 5-HT. Halothane inhibited synaptosomal accumulation of 5HT in a concentration-dependent manner, but had little effect on the passive or spontaneous release of the accumulated 5-HT. Rates of uptake of 5HT were inhibited by 43% in the presence of 1 mM halothane and by 75% of control in the presence of 5 mM halothane; the apparent I50 for halothane was 1.0 +/- 0.1 mM and Lineweaver-Burk analysis indicated the inhibition to be competitive at concentrations around the I50.
We used an habituation procedure to explore newborns' ability to detect successive changes in luminance and based on those data, their ability to discriminate chromatic from achromatic stimuli. Newborns were very insensitive to successive changes in luminance: after habituating to a white square of given luminance, they showed no evidence of dishabituating when the luminance of the square increased or decreased by 0.37 log cd/m2, but dishabituated only to the next larger difference of 0.53 log cd/m2. Moreover, after newborns were habituated to a series of white squares that varied widely in luminance, they did not react when the luminance of the square was increased as much as 0.71 log cd/m2. In the color vision experiments, infants were habituated to a series of white squares of varying luminance and then tested with a chromatic square and with a white square of novel luminance. The size of the squares was also varied. The results showed that newborns discriminated 8 deg red (lambda peak = 650 nm) and 16 deg green (lambda peak = 540 nm) squares from white but required a larger stimulus (16 deg) to demonstrate the discrimination of yellow (lambda peak = 585 nm) from white. In addition, newborns showed no evidence of discriminating a 32 deg blue (lambda peak = 470 nm) square from white. Thus, although the results imply that newborns are at least dichromats, they also show that their color vision mechanisms are immature, particularly those operating in the blue and yellow spectral regions.
We used the Teller Acuity Cards (TAC) to test 7 groups of 20 healthy infants and children ranging in age from 1 week to 36 months. We also tested 27 of these children at least twice within their first year. We had two primary goals: (1) to provide normative data on the development of visual acuity as assessed with the new version of the TAC (Vistech, Inc.) and (2) to investigate the predictive value of the TAC. The results from the cross-sectional samples show that our estimates of visual acuity are consistent with those reported by other researchers who used earlier versions of the TAC. The longitudinal data indicate that, on the average, an early estimate of visual acuity was not predictive of a later estimate, at least within the first year. The results are discussed in terms of the usefulness of the TAC for testing normal and clinical populations.
Data from this retrospective study indicate that a positive two-color T and/or B cell flow cytometric crossmatch (FCXM) is predictive of early renal allograft loss (less than 2 months) in cadaveric kidney donor recipients who had a negative crossmatch by the antihuman globulin complement-dependent cytotoxicity technique. Among 90 cadaveric kidney donor recipients (67 primary, 23 regrafts), 14 (8 primary, 6 regrafts) lost their renal allografts within 2 months, and 10 of the 14 were FCXM positive and HLA sensitized. The remaining 76 allografts survived beyond 2 months, 12 of which were FCXM-positive. Thus, the FCXM sensitivity rate for detecting early graft loss was 71%, and the specificity rate was 84%. Cadaveric graft-loss rates at 2 months were 33% for primary and 60% for FCXM-positive regrafts in contrast to 7% for primary and 0% for FCXM-negative regrafts. The difference in early graft loss between FCXM-positive and FCXM-negative recipients was statistically significant (P less than 0.0001). Subset analyses of FCXM-positive graft recipients indicate: (1) previous early graft loss contraindicates transplantation of an FXCM-positive regraft (P = 0.03); and (2) panel reactive antibody (PRA) less than or equal to 10% at crossmatch is not associated with early graft loss (P = 0.04). There was no significant difference in 1-year graft survival between primary and regrafts in either FCXM-negative recipients (85% vs. 77%, respectively) or FCXM-positive recipients (67% vs. 40%). All 12 of the FCXM-positive primary and regrafts that survived 2 months continued to function at 2 years. Stepwise logistic regression analysis of 5 independent predictor variables (FCXM status, gender, primary vs. regraft status, PRA level, and HLA mismatched antigens) indicated that the FCXM test was the best predictor of early graft loss. When FCXM results of the 90 cadaveric graft recipients were ranked in three groups, an FCXM channel shift of 29 or greater (third tertile) on a 1024 channel log scale was associated with a 7.0-fold (95% confidence interval 1.9-25.5) increased risk of early graft failure when compared to the first two tertiles. These data indicate that the FCXM offers an additional approach for identifying sensitized patients at risk of early renal allograft loss.
Ischemic stroke is a common and disabling complication of sickle cell disease (Hb SS). Most infarctions occur in the presence of intracranial stenotic lesions of the large vessels of the circle of Willis. Transcranial Doppler (TCD), by measuring flow velocity in these arterial segments, can detect focal stenosis on the basis of elevated flow velocity. We report the preliminary results of a prospective study to develop criteria for detection of stenotic lesions based on TCD and identification of patients with Hb SS at risk for stroke. Comparing the TCD findings from six patients with lesions demonstrated by angiography to those from 115 Hb SS children without stroke, we conclude: (a) middle cerebral (MCA), anterior cerebral (ACA), or internal carotid (ICA) artery mean velocities greater than 190 cm/s strongly suggest focal stenosis; (b) MCA or ACA mean velocities of 150 to 190 cm/s suggest abnormality but at present cannot be considered diagnostic of stenosis; (c) mean velocities up to 150 cm/s are possibly due to the effects of low hematocrit and/or young age, and cannot as yet be distinguished from velocity elevations due to vessel stenosis.
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Clinical and necropsy findings in 11 patients with sickle cell anemia (SS) indicate that intracranial hemorrhage (IH) is a delayed sequela of the same vasculopathy that causes cerebral infarction during childhood. Evidence of prior cerebral infarction during childhood included hemiparesis, seizures, an episode of coma, or mental retardation. Computerized tomography (CT) scans showed cerebral infarcts with lucent areas and dilated ventricles or cerebral atrophy. CT or magnetic resonance imaging (MRI) scans after the intracranial hemorrhage demonstrated intraventricular or intracerebral hemorrhages. Angiography or autopsy in seven patients showed widespread vascular occlusion and narrowing of arterial vessels. Moyamoya with internal carotid artery occlusion was identified in two cases. At the time of the IH, three patients were being treated with prophylactic transfusion regimens. We hypothesize that the central nervous system vasculopathy progresses over time and that arterial narrowing in both large and small vessels secondary to endothelial hyperplasia is followed by neovascularization and hemorrhage. Recognition of this pattern of delayed intracranial hemorrhage following cerebral infarction should encourage more intensive evaluation aimed at developing rational interventional therapy prior to a terminal intracranial hemorrhage.