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Biomedical subjects

R J Adams

Publications and source records attributed to R J Adams.

At least 91 records · Page 5Linked to original sources

Visual acuity in infants and children with Down syndrome.

The authors used the Teller acuity cards to assess the visual acuity of 51 infants and children with Down syndrome aged between two months and 18 years. The success rate and test times were comparable to those reported for normally developing children. Even those subjects in the study who were free of ocular disorders and/or who were wearing optical correction during testing showed significantly poorer visual acuity than individuals without Down syndrome. The development of visual acuity in infants and children with Down syndrome lags behind that of age-matched peers without Down syndrome, especially after the age of six months. These findings are discussed in terms of the neurological and optical factors that might account for the deficits in visual acuity that were observed.

Adolescent↗

Transcranial Doppler correlation with angiography in detection of intracranial stenosis.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the use of velocity criteria applied to transcranial Doppler (TCD) signals in the detection of stenosis of the middle cerebral (MCA), distal vertebral, and basilar arteries. METHODS: Sixty-five patients who underwent both cerebral angiography and transcranial Doppler examinations in the workup of acute cerebral ischemia were reviewed. Angiography was performed a mean of 7 +/- 5 days (range, 1 to 28 days) after TCD. Interpretation of the angiogram was performed without input regarding the TCD findings. TCD interpretation was performed according to standard criteria. RESULTS: When we used a mean velocity (MV) cutoff of > or = 80 cm/s in the MCA as the criterion for stenosis, 10 of 12 stenoses of any degree were detected by TCD, with 11 of 87 false-positives. Nine of 12 MCA stem (M1) stenoses were detected when a cutoff of > or = 90 cm/s was used, with 7 of 87 false-positives. When we used an MV cutoff of > or = 70 cm/s as the criterion for > or = 50% stenosis of the vertebrobasilar system, 5 of 6 stenoses were detected, with 15 of 85 false-positives. The most important confounding factor was the presence of > or = 75% stenosis of the extracranial internal carotid artery, resulting in both false-positive (from collateral flow) and false-negative (decreased volume flow from the proximal stenosis without adequate collateral flow) errors in TCD interpretation. When patients with > or = 75% stenosis of the cervical internal carotid artery were excluded from analysis, a TCD MV cutoff of > or = 80 cm/s identified 9 of 10 M1 lesions with 7 of 61 false-positives, and an MV of > or = 70 cm/s identified 3 of 4 vertebrobasilar lesions causing > or = 50% stenosis with 7 of 56 false-positives. CONCLUSIONS: TCD may be an effective screening test for M1 stenosis when velocity criteria alone are used. TCD may less reliably detect intracranial vertebral and basilar artery stenosis.

Adult↗

Neuropsychological impairment in children with sickle cell anemia and cerebrovascular accidents.

Neuropsychological functioning of children with sickle cell anemia (HbSS) who have experienced a single stroke has not been extensively investigated. In this study, the neuropsychological functioning of 10 children with HbSS who were receiving transfusion therapy following stroke with no identifiable recurrence was examined. The patients were subgrouped into children with only left hemisphere stroke (LCI), N = 4, and those with only right hemisphere stroke (RCI), N = 6. Results indicated that these youngsters experienced significant impairments of cognitive functioning following stroke. It was found that the LCI and RCI children tended to perform more like adult stroke patients than what has been typically reported in children with infantile hemiplegia. These findings support the need for periodic neuropsychological evaluation following stroke in order to identify patterns of higher cortical dysfunction and assist in the development of appropriate rehabilitation and special education programs. Further, pediatricians, child neurologists, and psychologists who care for these children must act as strong advocates on their behalf in order to ensure that they receive appropriate rehabilitation and the special education services necessary for maximal recovery and future educational success.

Adolescent↗

Antigenic variation of molecularly cloned SIVmac239 during persistent infection in a rhesus macaque.

Eight rhesus macaques inoculated with molecularly cloned SIVmac239 developed viremia and virus-binding antibodies, but only one (macaque 2D) developed neutralizing antibodies to the virus. Viremia persisted in macaque 2D even in the presence of neutralizing antibodies. Neutralizing antibodies in the plasma collected from macaque 2D late in infection neutralized virus isolated early in infection. In contrast, these antibodies failed to neutralize the plasma viruses isolated after the appearance of neutralizing antibodies. Only antigenic variants were isolated from blood, spleen, and lymph nodes. Viruses isolated from other macaques that did not develop neutralizing antibodies were neutralized by 2D serum and were of the parental (SIVmac239) phenotype. The variant viruses maintained their strict tropism for lymphocytes, similar to the parental virus.

Animals↗

Contrast sensitivity in 24- and 36-month-olds as assessed with the contrast sensitivity card procedure.

We used a new card procedure to evaluate binocular contrast sensitivity (CS) in 24- and 36-month-old children. The test consists of 40 large (50 by 28 cm) matteboard cards, each of which contains a sine wave grafting with 1 of 5 spatial frequencies (0.4, 0.8, 1.6, 3.2, and 4.8 cpd at 80 cm) and with 1 of 8 contrast levels [from 33% (CS = 3) to 0.4% (CS = 260)]. Estimates of subjects' CS to each spatial frequency were obtained with a modified forced-choice preferential looking (FPL) technique similar to that developed for the Teller Acuity Cards (TAC). All 36-month-olds and 74% of the 24-month-olds completed the entire procedure in an average of 12 min per child. For both groups, the shape of the mean constant sensitivity functions (CSF's) resembled the characteristic inverted U shown by normal adults, except that the toddlers' functions were shifted to lower contrasts and spatial frequencies. Combined with previous results, it appears that the CS cards hold promise as a time-efficient means of assessing CS in infants and young children, and may provide the prototype for a clinical tool to help detect early visual and neurological dysfunction.

Child, Preschool↗

Focal headache during balloon inflation in the vertebral and basilar arteries.

BACKGROUND AND PURPOSE: Headache may be seen in acute cerebrovascular disease. The significance of localized headache in association with vertebrobasilar disease has not been recognized. SUMMARY OF REPORT: We describe a patient with a cerebellar arteriovenous malformation who underwent intravascular balloon occlusion of the vertebral and basilar artery. He developed reproducible patterns of referred pain with balloon inflation at specific sites. CONCLUSIONS: Well localized head pain in the setting of acute stroke should alert physicians to the possibility of localized arterial injury. The pattern seen in this patient has been documented in experimental situations, and should be of use in the setting of acute stroke.

Basilar Artery↗

Increased immunoglobulin binding to cerebral endothelium in patients with antiphospholipid antibodies.

BACKGROUND AND PURPOSE: There is a strong link between antiphospholipid antibodies and stroke. The mechanism of action of antiphospholipid antibodies is unknown. Most theories of pathogenesis center around platelet or endothelial cell dysfunction. Our aim was to determine if there were immunoglobulins in the sera of patients with antiphospholipid antibodies that bind human brain microvascular endothelial cells. METHODS: We studied sera from three groups of subjects: patients with antiphospholipid antibodies and stroke (group 1), healthy control subjects (group 2), and patients with stroke but without antiphospholipid antibodies (group 3). We isolated human brain microvascular endothelial cells from temporal lobectomy specimens and used a cellular enzyme-linked immunosorbent assay (ELISA) to measure immunoglobulin binding to endothelial cells derived from human brain and from human umbilical vein. We used a chromium release assay to measure cytotoxicity. RESULTS: Patients with antiphospholipid antibodies and stroke had significantly higher immunoglobulin binding to human brain microvascular endothelial cells than subjects in the other groups ([ELISA index+standard deviation], 63 +/- 37 [group 1] versus 7 +/- 7 [group 2] versus 7 +/- 7 [group 3], P < .001). There was, however, poor correlation between binding to brain endothelial cells and binding to cardiolipin. The binding to brain microvascular cells was not specific to brain endothelium, as similar results were found in an ELISA using human umbilical vein cells. There was no evidence of complement-mediated brain endothelial cell cytotoxicity. CONCLUSIONS: Patients with stroke and antiphospholipid antibodies frequently have human brain microvascular endothelial-reactive antibodies in their serum. These antibodies are distinct from those to cardiolipin. We found no evidence that these antibodies are cytotoxic.

Adult↗

Coronary artery disease, myocardial infarction, and brain embolism.

The incidence of in-hospital stroke complicating acute myocardial infarction is approximately 1%. This rate is largely unaffected by thrombolytic therapy. Large myocardial infarctions, anterior wall involvement, prior stroke, and increasing age are risk factors for ischemic stroke. Left ventricular thrombi commonly occur with anterior wall infarctions. There is some evidence that anticoagulation reduces their incidence and uncontrolled studies suggest that anticoagulation may reduce the risk of embolization. Left ventricular aneurysms have a low rate of embolization and do not require systemic anticoagulation. Treatment of acute myocardial infarction with t-PA and anisoylated plasminogen streptokinase activator complex are associated with a higher risk of stroke than treatment with streptokinase; this excess risk is attributable to an increased rate of cerebral hemorrhages.

Brain↗

Pathogenesis of acute infection in rhesus macaques with a lymphocyte-tropic strain of simian immunodeficiency virus.

The simian immunodeficiency virus, SIVmac, causes disease affecting multiple organ systems in macaques similar to human immunodeficiency virus infection in humans. Molecularly cloned SIVmac with a strong lymphocyte tropism was used in pathogenesis experiments to correlate viral cell tropism with disease. In 5 animals, exhaustive analyses on viruses from tissues and identification of infected precursor cells were done at multiple times during infection to ensure the virus had not mutated into a macrophage-tropic variant. Viral replication was measured by infectivity, infectious center assays, and in situ hybridization. Lymphocytes produced most virus in tissues, indicating the virus maintained its cell tropism in vivo. Lymphocytes in bone marrow were latently infected and those in the spleen and lymph nodes were productively infected. The virus failed to replicate in the brain after intracerebral inoculation. SIVmac that maintained a strong tropism for lymphocytes and a corresponding poor tropism for macrophages can cause persistent infection and AIDS but not other diseases such as primary pneumonia and encephalitis in rhesus macaques.

Acute Disease↗

A new technique to measure contrast sensitivity in human infants.

We used a new time-efficient procedure to obtain binocular contrast sensitivity functions (CSFs) from 80 infants aged 1-, 3-, 6-, and 12-months-old. The test consisted of 5 sets of large (50 by 28 cm) cards constructed by mounting a 7.2 degrees circular sine wave grating with 1 of 5 spatial frequencies (0.3, 0.6, 1.2, 2.4, and 3.6 cpd at 60 cm) onto light gray matteboard. Each card also contained a second 7.2 degrees unpatterned patch of equal space-average luminance. Depending upon the set, the contrast within the gratings ranged from approximately 25 to 0.5%. To judge the subject's detection of each grating we used a rapid version of preferential looking (PL) similar to that developed for the Teller Acuity Cards. Results showed that compared to previous techniques, the card procedure allows one to estimate an infant's CSF much more simply, rapidly, and inexpensively.

Contrast Sensitivity↗

Tumour necrosis factor and interleukin 6 production during interaction between activated CD4+ lymphocytes and simian immunodeficiency virus-infected macrophages.

The mechanism for the gradual loss of CD4+ T lymphocytes and the development of the slowly progressive inflammatory/degenerative lesions that accompany human immunodeficiency virus infection are poorly understood. Using the Simian immunodeficiency virus (SIVmac) macaque model of AIDS, we found that persistently infected primary macrophages fuse with primary activated CD4+ lymphocytes and that this interaction results in production of tumour necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected macaque macrophages fuse with CEM174 cells (a human CD4+ cell line) and cause their lysis. In the present report, we have shown that TNF-alpha and IL-6 are also produced during the early stages of this interaction. Data from cocultivation of infected macrophages with several CD4+ T cell lines, including CEM174, suggested that the cytokines are produced by the T cells, and that cytokine production is restricted to those cells which not only express CD4, but are also capable of fusing with the infected macrophages. These data suggest that infected macrophages in vivo could fuse with and eliminate activated CD4+ lymphocytes and, during this interaction, release cytokines, which would contribute to the degenerative and inflammatory lesions characteristic of this disease.

Animals↗

Obstetrical medication and the newborn infant. II: The influence of meperidine (pethidine) on visual behaviour.

The visual fixation of two groups of healthy newborn infants was tested at a mean age of three days. Mothers of the infants in one group received a single dose of meperidine (pethidine) during labour and delivery; those in the second group received no medication. Unlike infants of mothers who received a single dose of alphaprodine hydrochloride in a previous study, there were no differences between the groups in the present study. Moreover, longer drug-to-delivery intervals did not appear to potentiate the effects of meperidine. A single dose of meperidine appears to have few effects on neonates' sensory functioning, which is contrary to other reports.

Alphaprodine↗

Neutralizing antibodies modulate replication of simian immunodeficiency virus SIVmac in primary macaque macrophages.

Cultured macaque macrophages are permissive for the replication of SIVmac251, and inoculation with virus is followed by the production of viral p27. Neutralizing macaque polyclonal and murine monoclonal antibodies preincubated with the virus prevented infection but did not prevent cytopathic virus replication when added more than 3 days after inoculation with virus. However, application of the neutralizing antibodies to macrophages 24 h after inoculation with virus resulted in sustained, low-level production of viral antigen. Cell lysates and individual macrophages from treated cultures contained less viral protein by Western blot (immunoblot) and immunocytochemistry than untreated controls. In situ hybridization and polymerase chain reaction procedures for detecting and estimating relative amounts of viral RNA and DNA showed that both viral nucleic acids failed to increase beyond the levels obtained before the addition of neutralizing antibodies. The data suggest that macrophages may need to be infected with a minimum threshold of virus particles in order to reach their full potential for virus replication and that their exposure to neutralizing antibodies prior to reaching this threshold resulted in limited virus replication.

Animals↗

Ovine lentivirus is macrophagetropic and does not replicate productively in T lymphocytes.

The lentiviruses of sheep, goats, and horses cause chronic multiorgan disease in which macrophages are highly permissive for viral replication. Monocytes, which mature into macrophages, are thought to be latently infected with lentivirus, but the extent to which other leukocytes are infected is unknown. Dendritic cells have not been studied separately from monocytes and T-cell subsets have not been examined in previous attempts to identify infected cells in peripheral blood mononuclear cells (PBMC). We found no evidence of T-cell tropism using an animal-passaged, pathogenic ovine lentivirus. Phytohemagglutinin-stimulated infectious PBMC produced 20-fold less virus than differentiated macrophages, and cocultivation of infectious PBMC with fresh, uninfected phytohemagglutinin blasts did not facilitate virus replication. Furthermore, central lymph cells, the best in vivo source of purified lymphocytes, lacked virus and did not yield virus upon in vitro cultivation. In contrast, cultivated blood-derived macrophages were highly permissive for viral replication. To identify the latently infected PBMC, PBMC from infected sheep were selectively depleted of monocytes and B cells by passage over nylon wool and then of nonadherent cells bearing CD4, CD8, T19, gamma delta T-cell receptor, CD45RA, or major histocompatibility complex class II antigens by panning. Removal of adherent monocytes and B cells or of adherent cells and the three major T-cell subsets (CD4+, CD8+, T19+) did not decrease the infectivity of PBMC. The richest sources of infected cells in fresh PBMC were CD45RA+ and major histocompatibility complex class II+ nonadherent cells, which are three characteristics of dendritic cells. Thus, the dendritic cell, and not the monocyte or the CD4+ cell, is probably the predominant infected cell type in blood.

Animals↗

Transcranial Doppler correlation with cerebral angiography in sickle cell disease.

BACKGROUND AND PURPOSE: Cerebral infarction in sickle cell disease is associated with arterial narrowing or occlusions of intracranial arteries. Primary stroke prevention would be feasible if a noninvasive screening test could be developed to detect intracranial disease in patients before symptoms develop. METHODS: To determine the sensitivity and specificity of transcranial Doppler in detecting significant (greater than or equal to 50% lumen diameter reduction) intracranial arterial lesions, we compared transcranial Doppler and cerebral angiography in a primarily young, symptomatic group of 33 patients (18 males and 15 females) with sickle cell disease. RESULTS: From a total of 34 examinations, transcranial Doppler detected significant abnormalities in 26 of 29 (sensitivity 90%, specificity 100%). Five were normal by both techniques. The transorbital examination detected abnormalities in two patients whose studies were otherwise unremarkable. CONCLUSIONS: Transcranial Doppler is sensitive and specific for the detection of arterial vasculopathy of sickle cell disease. Screening should include a transorbital examination of the distal internal carotid artery as well as examination using the transtemporal approach.

Adolescent↗