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Biomedical subjects

R J Adams

Publications and source records attributed to R J Adams.

At least 55 records · Page 3Linked to original sources

Sterilization and disinfection in general practice in Northern Ireland.

In view of the recent trend towards more minor surgery being carried out in general practice we decided to conduct a postal survey to assess the level of knowledge of sterilization and disinfection and the use of benchtop sterilizers in general practice in Northern Ireland. The survey, of all 366 practices in the Province, was carried out in January/March 1998. One hundred and eleven (30%) completed questionnaires were returned. All practices performed at least one of a range of procedures requiring sterilization or disinfection, e.g., minor surgery 95%, cervical smear taking 98%, syringing of ears 98%. Only 76% of practices had a benchtop sterilizer and 39% did not have access to a sterile supply department (SSD); 32% of the latter had no desire to utilize such a service. Only 25% and 34% correctly identified the Medical Devices Agency (MDA) definitions of sterilization and disinfection respectively. The MDA Device Bulletin on benchtop sterilizers had been read by only 26% of respondents. There was an 86% interest in attending a workshop on sterilization and disinfection. The concepts and practice of sterilization and disinfection appear not to be clearly understood. We conclude that resources must be identified to provide appropriate education in this important area for primary care staff.

Ambulatory Surgical Procedures↗

Measles virus infection in rhesus macaques: altered immune responses and comparison of the virulence of six different virus strains.

Measles remains a major cause of childhood mortality, with questions about virus virulence and pathogenesis still requiring answers. Rhesus macaques were infected with 5 different culture-adapted strains of measles virus, including 2 from patients with progressive vaccine-induced disease, and a sixth nonculture-adapted strain, Bilthoven. All caused infection detectable by reverse transcriptase-polymerase chain reaction and induction of antibody. Chicago-1 and Bilthoven induced viremias detectable by leukocyte cocultivation. Bilthoven induced Koplik's spots, conjunctivitis, and rash. Lymphopenia and depressed interleukin (IL)-2 production were followed by monocytosis and eosinophilia. All monkeys, including 41 involved in a primate facility outbreak, showed suppressed responses to phytohemagglutinin. As the rash resolved production of IL-2, IL-1beta, tumor necrosis factor-alpha, IL-6, and IL-5 mRNA increased. Monkeys are useful for studies of measles immunopathogenesis, but virus strains must be carefully chosen. Increased virulence of vaccine strains isolated from immunocompromised infants with fatal infections was not evident.

Animals↗

High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis.

AIDS dementia and encephalitis are complications of AIDS occurring most frequently in patients who are immunosuppressed. The simian immunodeficiency virus (SIV) model used in this study was designed to reproducibly induce AIDS in macaques in order to examine the effects of a neurovirulent virus in this context. Pigtailed macaques (Macaca nemestrina) were coinoculated with an immunosuppressive virus (SIV/DeltaB670) and a neurovirulent molecularly cloned virus (SIV/17E-Fr), and more than 90% of the animals developed moderate to severe encephalitis within 6 months of inoculation. Viral load in plasma and cerebrospinal fluid (CSF) was examined longitudinally to onset of AIDS, and viral load was measured in brain tissue at necropsy to examine the relationship of systemic and central nervous system (CNS) viral replication to the development of encephalitis. In all animals, plasma viral load peaked at 10 to 14 days postinfection and remained high throughout infection with no correlation found between plasma viremia and SIV encephalitis. In contrast, persistent high levels of CSF viral RNA after the acute phase of infection correlated with the development of encephalitis. Although high levels of viral RNA were found in the CSF of all macaques (six of six) during the acute phase, this high level was maintained only in macaques developing SIV encephalitis (five of six). Furthermore, the level of both viral RNA and antigen in the brain correlated with the severity of the CNS lesions. The single animal in this group that did not have CNS lesions had no detectable viral RNA in any of the regions of the brain. The results substantiate the use of CSF viral load measurements in the postacute phase of SIV infection as a marker for encephalitis and CNS viral replication.

Animals↗

Alterations in blood-brain barrier glucose transport in SIV-infected macaques.

The neurological manifestations of HIV infection may be in part due to alterations in the blood-brain barrier. These may be caused by structural changes in the barrier or may consist of subtle metabolic or biochemical disturbances in barrier function. In the CNS, the family of glucose transporter proteins plays a key role in controlling movement of glucose across cell membranes. The 55 kDa isoform of glucose transporter 1 (GLUT1) regulates import of glucose from blood to brain across the endothelial cells of the blood-brain barrier (BBB), whereas the 45 kDa form of GLUT1 predominantly regulates nonvascular glial glucose uptake. In this study, expression of 55 and 45 kDa forms of GLUT1 in different regions of the brain from 18 SIV-infected macaques was measured by quantitative immunoblot and then compared with the severity of SIV encephalitis to determine whether neurologic disease is related to altered glucose metabolism at the BBB and in brain parenchyma. An inverse relationship was found between severity of SIV encephalitis and expression of the endothelial 55 kDa isoform of GLUT1 at the BBB in cortical grey matter, caudate nucleus, and cerebellum. A similar relationship also was found for the glial 45 kDa GLUT1 isoform in cortical grey matter. In addition, a significant increase in 55 kDa GLUT1 expression was found in caudate nucleus during the early stages of infection. In the brains of macaques with moderate to severe encephalitis, 55 kDa GLUT1 expression had declined to pre-infection levels. These GLUT1 alterations at the BBB and in glial cells may reflect severe disturbances in the CNS microenvironment that contribute to CNS dysfunction.

Animals↗

Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography.

BACKGROUND: Blood transfusions prevent recurrent stroke in children with sickle cell anemia, but the value of transfusions in preventing a first stroke is unknown. We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then randomly assigned them to receive standard care or transfusions to prevent a first stroke. METHODS: To enter the study, children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher. The patients were randomly assigned to receive standard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration. The incidence of stroke (cerebral infarction or intracranial hemorrhage) was compared between the two groups. RESULTS: A total of 130 children (mean [+/-SD] age, 8.3+/-3.3 years) were enrolled; 63 were randomly assigned to receive transfusions and 67 to receive standard care. At base line, the transfusion group had a slightly lower mean hemoglobin concentration (7.2 vs. 7.6 g per deciliter, P=0.001) and hematocrit (20.4 vs. 21.7 percent, P=0.002). Ten patients dropped out of the transfusion group, and two patients crossed over from the standard-care group to the transfusion group. There were 10 cerebral infarctions and 1 intracerebral hematoma in the standard-care group, as compared with 1 infarction in the transfusion group -- a 92 percent difference in the risk of stroke (P<0.001). This result led to the early termination of the trial. CONCLUSIONS: Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography.

Adolescent↗

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↗

Pathogenesis of simian immunodeficiency virus pneumonia: an immunopathological response to virus.

Although many human immunodeficiency virus-infected individuals develop lymphocytic interstitial pneumonia, the roles of host and viral factors in the pathogenesis of pneumonia are not well defined. Human immunodeficiency virus-infected children with lymphocytic interstitial pneumonia have human immunodeficiency virus-specific cytotoxic T cells in pulmonary infiltrates, increased survival time, and a reduced incidence of opportunistic infections, suggesting that lymphocytic interstitial pneumonia may reflect an effective antiviral immune response. In this study, 20 macaques were inoculated with related macrophage-tropic simian immunodeficiency viruses and examined for pulmonary lesions and virus gene expression. Ten macaques developed moderate to severe pneumonia characterized by perivascular, peribronchial, and interstitial infiltrates of lymphocytes and macrophages. Large numbers of pulmonary cytotoxic lymphocytes were demonstrated in macaques with moderate to severe pneumonia (P < 0.05) by immunostaining for TIA-1. There was no difference in viral load between macaques with moderate to severe pneumonia and those with mild to no pulmonary lesions. In five macaques inoculated with the same virus swarm, there was a significant (P < 0.05) inverse correlation between the percentage decline in CD4+ T-cell counts and the severity of pulmonary lesions. Pulmonary infiltrates of cytotoxic lymphocytes, the lack of correlation between severity of pulmonary lesions and virus gene expression, and the inverse relationship between pneumonia and inmune status suggest that simian immunodeficiency virus pneumonia may represent an immunopathological response to macrophage-tropic virus.

Animals↗

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↗

A modified card procedure for measuring human infant color vision.

To improve test efficiency, we modified our previously introduced contrast/color card test by including a patterned test stimulus and reducing the number of stimuli in both experimental phases. Compared with the prototype, completion rate improved substantially (79 vs. 37%) but test time decreased only modestly (19 vs. 21 min). Achromatic contrast discrimination improved threefold (mean, 0.06 vs. 0.20 log units), but the percentage of 2-month-old infants who discriminated (from gray) 660-nm red (86 vs. 80%) and 580-nm yellow (52 vs. 55%) was consistent. In addition, 48% discriminated 574-nm yellow-green. Moreover, because 88% of infants' failures included the respective adult brightness/luminance match, a small range of relative luminances is adequate for testing infant color vision.

Color Perception↗

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↗

Measuring individual differences in change with multidimensional Rasch models.

Item response models have been developed to explore change measurement, including those proposed by Fischer and his colleagues (e.g., Fischer & Pazer, 1991; Fischer & Ponocny, 1994), Andersen (1985) and Embretson (1991). In this article, we propose another multidimensional Rasch model, the multidimensional random coefficient multinomial logit (MRCML) model (Adams, Wilson, & Wang, 1997). All these models are briefly reviewed and compared. The MRCML can be applied to not only polytomous items but also investigation of variations in item difficulties. Based on variations in difficulties across occasions and items, five kinds of models are proposed. Some simulation studies were conducted to examine parameter recovery of the MRCML model under various testing situations. All the parameters were recovered very well. A real data set was analyzed to show applications of the MRCML to measuring individual differences in change.

Australia↗

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↗