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Biomedical subjects

R J Adams

Publications and source records attributed to R J Adams.

At least 19 recordsLinked to original sources

Human newborn color vision: measurement with chromatic stimuli varying in excitation purity.

Groups of newborn human infants (N = 180) were habituated to large 16 degrees achromatic ("white") lights of varying luminance (0.35 to 1.16 log cd/m2) and then tested for recovery of habituation to 16 degrees green (dominant lambda = 545 nm), yellow (dominant lambda = 585 nm) or red (dominant lambda = 650 nm) lights which varied in the level of excitation purity (range = 32 to 83%). Results showed that newborns discriminated the chromatic stimuli from white only when excitation purity values exceeded at least 41% for 545-nm green, 47% for 650-nm red, and 65% for 585-nm yellow, limits much higher than those for adults (<1%). Taken together with the results from previous experiments, these saturation discrimination data (with the exception of the yellow data), provide some support for an expanded MacAdam ellipse model of early color discrimination (Brown, 1993; Teller & Lindsey, 1993). This helps reinforce the current view that neonates' vision is based on general rather than selective immaturities or inefficiencies within the requisite optical, photoreceptoral and neural mechanisms.

Analysis of Variance

Stroke prevention trial in sickle cell anemia.

Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of > or = 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS.

Adolescent

Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators.

BACKGROUND AND PURPOSE: Medical and neurological complications after acute ischemic stroke may adversely impact outcome and in some cases may be preventable. Limited data exist regarding the frequency of such complications occurring in the first days after the ictus and the relationship of these complications to outcome. Our objective was to identify the types, severity, and frequency of medical and neurological complications following acute ischemic stroke and to determine their role in mortality and functional outcome. METHODS: Rates of serious (life-threatening) and nonserious medical and neurological complications and mortality were derived from the placebo limb of the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS) database (n=279). Complications were correlated with clinical outcome using logistic regression techniques. RESULTS: Of all patients, 95% had at least one complication. The most common serious medical complication was pneumonia (5%), and the most common serious neurological complication was new cerebral infarction or extension of the admission infarction (5%). The 3-month mortality was 14%; 51% of these deaths were attributed primarily to medical complications. Outcome was significantly worse in patients with serious medical complications, after adjustment for baseline imbalances, as measured by the Barthel Index (odds ratio [OR], 6.1; 95% confidence interval [CI], 2.5 to 15.1) and by the Glasgow Outcome Scale (OR, 11.6; 95% CI, 4.3 to 30.9). After death was discounted, serious medical complications were associated with severe disability at 3 months as determined by the Glasgow Outcome Scale (OR, 4.4; 95% CI, 1.3 to 14.8). CONCLUSIONS: Medical complications that follow ischemic stroke not only influence mortality but may influence functional outcome.

Aged

Oriented cell divisions and cellular morphogenesis in the zebrafish gastrula and neurula: a time-lapse analysis.

We have taken advantage of the optical transparency of zebrafish embryos to investigate the patterns of cell division, movement and shape during early stages of development of the central nervous system. The surface-most epiblast cells of gastrula and neurula stage embryos were imaged and analysed using a computer-based, time-lapse acquisition system attached to a differential interference contrast (DIC) microscope. We find that the onset of gastrulation is accompanied by major changes in cell behaviour. Cells collect into a cohesive sheet, apparently losing independent motility and integrating their behaviour to move coherently over the yolk in a direction that is the result of two influences: towards the vegetal pole in the movements of epiboly and towards the dorsal midline in convergent movements that strengthen throughout gastrulation. Coincidentally, the plane of cell division becomes aligned to the surface plane of the embryo and oriented in the anterior-posterior (AP) direction. These behaviours begin at the blastoderm margin and propagate in a gradient towards the animal pole. Later in gastrulation, cells undergo increasingly mediolateral-directed elongation and autonomous convergence movements towards the dorsal midline leading to an enormous extension of the neural axis. Around the equator and along the dorsal midline of the gastrula, persistent AP orientation of divisions suggests that a common mechanism may be involved but that neither oriented cell movements nor shape can account for this alignment. When the neural plate begins to differentiate, there is a gradual transition in the direction of cell division from AP to the mediolateral circumference (ML). ML divisions occur in both the ventral epidermis and dorsal neural plate. In the neural plate, ML becomes the predominant orientation of division during neural keel and nerve rod stages and, from late neural keel stage, divisions are concentrated at the dorsal midline and generate bilateral progeny (C. Papan and J. A. Campos-Ortega (1994) Roux's Arch. Dev. Biol. 203, 178-186). Coincidentally, cells on the ventral surface also orient their divisions in the ML direction, cleaving perpendicular to the direction in which they are elongated. The ML alignment of epidermal divisions is well correlated with cell shape but ML divisions within the neuroepithelium appear to be better correlated with changes in tissue morphology associated with neurulation.

Animals

Long-term stroke risk in children with sickle cell disease screened with transcranial Doppler.

Stroke is an important complication of sickle cell disease. Stroke prediction is clinically important because it offers the possibility of primary prevention. In 1992, transcranial Doppler (TCD) evidence of elevated intracranial internal carotid or middle cerebral artery velocity was demonstrated to be associated strongly with an increased risk of ischemic stroke. This study extends the original study and includes 125 more children, longer follow-up, and intracranial hemorrhage in the stroke-risk model. Elevated time averaged mean maximum blood flow velocity, especially when velocity is 200 cm/sec or greater by TCD, was associated strongly with stroke risk. The cases not predicted by TCD point to the need for more information on the optimal timing of TCD surveillance for stroke risk.

Adolescent

Contrast sensitivity in infants and children with Down syndrome.

A new contrast sensitivity (CS) card test was used to estimate contrast sensitivity in 18 infants and children with Down syndrome (DS). The results showed that although the overall shape of the contrast sensitivity functions (CSFs) of the subjects with DS was the typical inverted-U, their CSFs were depressed in comparison to control subjects and this relative loss became larger with increasing spatial frequency. In addition, there was little improvement in CS with age and the mean CSF among children with DS (mean age = 7.3 years) was equivalent statistically to a group of 12-month-olds without DS. The Teller Acuity Cards (TAC) were also used to assess visual acuity in 17 of the 18 children in our sample. The results of these tests showed that their visual acuity (VA) was significantly lower than normal, but was consistent with that extrapolated from each subject's CSF. Taken together with previous anatomical and developmental findings, our results suggest that the deficits in spatial vision among children with DS is due primarily to restricted cortical development, and secondarily, to the additional accommodative and ocular conditions that are prevalent in this population.

Adolescent

Visual acuity in extremely low birth weight infants.

The increased viability of extremely low birth weight (ELBW) infants (those weighing less than 1,000 g) and the associated increased risk of visual impairment has highlighted the need for reliable indices of visual functioning for this population. By use of the Teller Acuity Cards, we assessed grating visual acuity in 26 survivors of extreme prematurity (corrected age, 2-42 mo) and found that although most scores were within the normal range, they were significantly lower than those of full-term infants of equivalent postconceptional age, especially after 9 months of age. Moreover, the number of complications in the neonatal period (especially bronchopulmonary dysplasia) and the Neonatal Medical Index classification were associated with below-average visual acuity in infancy and early childhood.

Birth Weight

Pathogenesis of ovine lentiviral encephalitis: derivation of a neurovirulent strain by in vivo passage.

The lentiviruses of sheep replicate almost exclusively in macrophages and cause chronic interstitial pneumonia, arthritis, and mastitis, but only rarely encephalitis. This study was undertaken to determine whether a non-neurovirulent field strain of ovine lentivirus isolated from joint fluid that replicated productively in lung and joint macrophages could be adapted to enter and replicate in the brain and cause encephalitis. The field isolate was passed seven times sequentially by intracerebral inoculation of sheep. The neuroadapted strain of virus caused severe encephalitis typical of visna in four of four sheep inoculated intracerebrally. The virus replicated to high titers in the brains of these animals and in cultured microglia. The inflammatory response in the brain was characterized by intense infiltrates of macrophages and CD8+ and CD4+ T cells. Many of the perivascular macrophages demonstrated TNF-alpha expression and there was upregulation of MHC Class II antigen expression on both inflammatory cells and endothelium. Inoculation of this neuroadapted virus into the bone marrow of three animals resulted in persistent infection and cell-associated viremia, but not encephalitis. Virus was not detected in brains from these animals, indicating that the virus was not neuroinvasive. These data suggest that neuroinvasiveness and neurovirulence are separate pathogenic determinants, both of which are required for the development of encephalitis during natural infection.

Animals

Metaphase spindles rotate in the neuroepithelium of rat cerebral cortex.

Time-lapse confocal microscopy has been used to image cells in mitosis at the apical surface of neuroepithelium from the rat cerebral cortex during the period of neurogenesis. Staining with vital chromatin dyes reveals that mitotic spindles that are aligned parallel to the surface of the tissue are highly motile, rotating within the plane of the epithelium throughout metaphase, and come to rest only as anaphase begins. Spindles may make several complete turns, parallel to the epithelium, but only rarely tumble into an orientation perpendicular to the epithelial sheet. Analysis shows that spindles do not rotate randomly; rather, they spend most of their time aligned parallel or antiparallel to the direction in which they will later enter anaphase and undergo cell division. This conclusion is strongly supported by statistical analyses of the data. Stereotyped movements of this kind show that the direction of division is determined early in mitosis. This suggests the existence of intracellular and perhaps intercellular signals that define the polarity of the cell both in the apico-basal direction and within the plane of the epithelium. Such mechanisms may be important for maintaining the structure of the epithelium and cell-cell communication during development and may also provide a mechanism for the precise distribution of cytoplasmic determinants that might influence the fate of the daughter cells at a time when neuronal fate is being determined.

Animals

Infant peripheral vision: the development of monocular visual acuity in the first 3 months of postnatal life.

Quantitative data on the early morphological development of the human retina show that the peripheral region is relatively more mature than the central region. These results have stimulated researchers to compare the development of visual functions in the central and peripheral regions of the visual field. Here, we used preferential looking to evaluate 1-, 2- and 3-month-old infants' central and peripheral (10 degrees and 30 degrees) monocular visual acuity. There were three findings: (i) both central and peripheral acuities were poor at 1 month, improved over the age range tested, but were still about 3 octaves worse than adults' acuity; (ii) at all ages monocular acuity decreased with increasing eccentricity; (iii) 2- and 3-month-olds showed higher acuity for gratings in the temporal than in the nasal visual field at 30 degrees. The implications of these results for issues in visual development are discussed.

Adult

Monocular contrast sensitivity in 3- to 36-month-old human infants.

A recently developed psychophysical "card" technique was used to evaluate monocular contrast sensitivity in ninety 3-, 6-, 12-, 24-, and 36-month-old human infants. Results showed that for 3-, 6-, 24-, and 36-month-olds, monocular contrast sensitivity functions were very similar to binocular contrast sensitivity functions estimated in a previous experiment. However, at 12-months, monocular contrast sensitivity functions were significantly lower (about 1 octave) than binocular contrast sensitivity functions, a trend also observed in developmental studies of visual acuity. This asymmetry suggests that the neural substrate underlying the development of monocular and binocular spatial vision undergoes different rates of development, at least during the months surrounding the end of the first postnatal year.

Aging

Stroke in children and young adults.

This selective review of stroke in children and young adults addresses: (1) stroke in sickle cell disease, particularly the prognostic use of transcranial Doppler, (2) oral contraceptives as a stroke risk factor, (3) stroke in pregnancy, and (4) the prognosis of ischemic stroke in young adults. Factors relevant to the primary prevention and outcome of stroke are emphasized.

Adolescent

Further exploration of human neonatal chromatic-achromatic discrimination.

Newborn (n = 140) and 1-month-old (n = 120) human infants were habituated to achromatic ("white") squares of varying luminance (.35 to 1.16 log cd/m2) and then tested for recovery of habituation with chromatic stimuli from particular spectral locations. Results showed that newborns appear to discriminate 32 degrees yellow-green (dominant lambda = 565 nm) from white, but not 16 degrees or 32 degrees blue (450 nm), 16 degrees blue-green (493 nm), 16 degrees or 32 degrees yellow-green (572 nm), or 16 degrees purple from white. Performance of 1-month-olds was marginally better than that of newborns. Combined with our previous results with the habituation method, these data imply that newborns show little ability to make any chromatic-achromatic discriminations when stimulus size is smaller than 8 degrees, and that even with very large stimuli (e.g. 32 degrees) performance is relatively poor in the blue and yellow-green spectral regions. Although several models were considered, these limitations in the short- and mid-wavelength regions may best be accounted for by the argument that young infants possess general rather than selective immaturities or inefficiencies within their chromatic mechanisms.

Child Development

Development of chromatic discrimination in early infancy.

Combining a habituation-recovery paradigm with procedures to minimize brightness cues, we evaluated 1-3-month-olds' ability to discriminate among broadband mid- and long-wavelength stimuli. One-month olds showed evidence of discriminating a red (dominant lambda = 650 nm) from green (dominant lambda = 545 nm) but failed to discriminate either of these from a yellow (dominant lambda = 585 nm). At 2 months, infants showed evidence of discriminating 545-nm green from 585-nm yellow, but only at 3 months do they appear to discriminate 650-nm red from the yellow. Consistent with previous work, these data imply that chromatic discrimination emerges slowly over the first three postnatal months. Moreover, the developmental pattern is consistent with the notion that early human vision is limited by general rather than selective immaturities within the requisite retinal and neural mechanisms.

Color Perception

Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions.

OBJECTIVE: To determine the effect of a transfusion program on risk of stroke recurrence in children with sickle cell disease. DESIGN: The clinical course and experience with transfusion therapy at eight centers were reviewed for subjects whose initial stroke occurred after January 1988. RESULTS: Sixty subjects were observed for 191.7 patient-years. Eight had a single recurrent stroke (two intracranial hemorrhages and six infarctions) for a prevalence of 13.3%, or one recurrence for each 24 patient-years of observation. Thirteen subjects had 15 transient neurologic events; two of these had subsequent strokes, but the overall risk was similar for those who did and those did not have transient events. Hemoglobin S levels were greater than the desired maximum of 30% at the time of 7 of 16 transient events and five of six recurrent infarctions. The stroke recurrence rate was similar to those in previous reports of children receiving long-term transfusion therapy but significantly less than that reported for children who did not receive transfusions (p < 0.001). CONCLUSIONS: We conclude that maintenance of hemoglobin S at a level less than 30% appears to be effective in reducing the rate of recurrent infarction but does not prevent transient neurologic events. Transient neurologic events are common but do not appear to be related to recurrent stroke.

Adolescent

Bile acid dysfunction after clam enterocystoplasty.

OBJECTIVE: To determine if the bowel dysfunction that develops in approximately 12% of patients after a clam enterocystoplasty is due to disruption of the enterohepatic circulation of bile acids. PATIENTS AND METHODS: Fourteen symptomatic patients (mean age 36 years, range 21-65) who had undergone clam enterocystoplasty were investigated by bowel frequency charts, hydrogen breath tests of expired air and the retention of radioactive 75Se-labelled homocholic acid-taurine (SeHCAT), a synthetic bile acid. Patients with abnormal results were commenced on anion-exchange resins and the symptoms evaluated 6 weeks later. RESULTS: The interruption of bile acid circulation, as estimated by SeHCAT, occurred in most of the patients studied and was due to surgical resection of the terminal ileum. All hydrogen breath tests were normal, excluding bacterial overgrowth as a cause of diarrhoea. Bowel frequency correlated well with the percentage of SeHCAT retained. Anion-exchange resins were successful in relieving the symptoms if patients complied well with the treatment. CONCLUSIONS: After clam enterocystoplasty, some patients have bowel dysfunction caused by the interruption of the enterohepatic circulation of bile acids. These patients can be identified using bowel frequency charts and treated by anion-exchange resins.

Adult