Deaths from hemolytic disease of the newborn.
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Biomedical subjects
Publications and source records attributed to P Flanagan.
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A prospective longitudinal study assessed the effects of intraventricular hemorrhage (IVH) and socioeconomic status on the perceptual, cognitive, and neurologic status of preterm infants at 5 years of age. The preterm group consisted of infants with no IVH, grade I to II IVH, and grade III to IV IVH; a control group of normal term infants was also studied. Outcome was evaluated at 3, 4, and 5 years of age. Twenty-four percent of infants with grade III to IV IVH had abnormal neurologic diagnoses at 5 years of age. Correlations of predictor variables including IVH status, latency of visual evoked response, days of hospitalization, and socioeconomic status with 5-year neurologic outcome indicated that IVH status and visual evoked response at 1, 2, and 3 years continued to have an effect on neurologic outcome, but socioeconomic status and days of hospitalization did not; socioeconomic status did have a significant effect on the McCarthy cognitive scores but not on the perceptual scores at 5 years. Multiple regression analyses revealed that duration of hospitalization (reflecting neonatal morbidity), visual evoked response, and socioeconomic status all have independent effects on the cognitive index, whereas only duration of hospitalization has an independent effect on the perceptual index. These data support the concept that a complex interaction of biologic and environmental risk factors determines the degree of recovery from IVH by high-risk preterm infants.
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Interleukin 2 (IL-2) has been demonstrated to generate lymphokine-activated killer (LAK) cells from normal human peripheral blood lymphocytes (PBL). Such LAK cells have demonstrated lytic activities on certain tumor cell targets including melanoma, renal carcinoma, and other tumor targets. B lymphoblastoid cell lines such as Raji cells are routinely employed to assess functional LAK cell activity. In our studies we have assessed the effect of various cytokines that affect lymphocyte cell growth and differentiation, including rIL-2, interleukin 4 (rIL-4), interleukin 6 (rIL-6), interferon alpha and gamma (rIFN-alpha and -gamma) and tumor necrosis factors alpha and beta (rTNF-alpha, rTNF-beta), for their ability to generate functional LAK cell activity. Our data confirm that rIFN-alpha and -gamma singularly are capable of inducing LAK cell activity (55 +/- 21 and 40 +/- 10, respectively, in comparison to rIL-2 at 1000 units/ml) whereas rIL-4, rIL-6, BCGF, rTNF-alpha, or rTNF-beta failed to generate the functional LAK cell activity from human PBL. Interferon alpha, itself capable of generating LAK cell activity, was augmentative in its effect with rIL-2 for the generation of functional LAK cell activity. Conversely, rIL-4 inhibited LAK cell activity induced by either rIL-2 alone or the combination of rIL-2 and rIFN-alpha. Furthermore, the increased effects of rIFN-alpha with rIL-2 on LAK cell activity are partly abrogated by as much as 30 or 52% by delaying the addition of either rIL-2 or rIFN-alpha, respectively, for more than 24 h. These results suggest a regulatory role for certain cytokines on LAK cell functions.
Since gastric acid is an important luminal factor in the absorption of non-heme iron, the effect of omeprazole on the absorption of iron in a rat model was studied. Iron absorption studies were performed on rats on a normal diet (N = 42) and rats fed an iron-deficient diet (N = 43) for three weeks. Rats were orally dosed with 40 mumol/kg of omeprazole or placebo daily for two days prior to iron absorption studies. Rats were orally dosed with 1 mmol of ferrous chloride, ferric chloride or food iron (dietary suspension) containing 11 micrograms of iron and labeled with 1 microCi of 59Fe. Omeprazole-treated rats on the normal diet had no significant reduction in the absorption of ferric, ferrous, or food iron. In the rats on the iron-deficient diet, the absorption of ferrous iron decreased from 76 +/- 7.5% (mean +/- SE) in control rats to 38 +/- 8.5% in the omeprazole-treated rats (P less than 0.003) and the absorption of food iron decreased from 65 +/- 7.5% in control rats to 37 +/- 6.5% in the omeprazole-treated rats (P less than 0.016). There was no significant reduction in the absorption of ferric iron. Omeprazole therapy is unlikely to be associated with significant iron malabsorption in normal patients but may reduce iron absorption in pathological states associated with increased iron absorption such as iron deficiency.
Visual channels are defined psychophysically; stimuli that interact share information in the same channel, and those that do not interact are processed in different channels. Channels are often investigated by means of adaptation to one stimulus, testing contrast threshold elevation with one (or more) others. Much recent work has tested the tuning of channels for orientation and spatial frequency, using simple line gratings. This study examined the pattern-specificity of such adaptation, testing the hypothesis that the fundamental operators of the Lie Transformation Group Theory of Neuropsychology (LTG/NP) define psychophysical channels. In Experiment I the three basic pattern pairs of LTG/NP were used as adaptation and test stimuli in a conventional contrast threshold-elevation experiment. Threshold elevation was pattern-specific, thus supporting the hypothesis. In subsequent experiments various 'fractured' patterns, and patterns generated by combinations of Lie operators were used both for adaptation and test. The results were mixed; some supported the original hypothesis, but many did not. Relations between local contour orientations in adaptation and test patterns could explain some results, but not all. The hypothesis that adaptation occurs to the oriented spatial-frequency components of the test patterns, on the other hand, gave a good fit to the data. It is concluded that there is pattern-specificity in contrast threshold elevation, but it is a form of specificity that can be explained without recourse to a model of geometrical pattern processing, at least for the simple patterns used here.
Simultaneous, oppositely tilted, aftereffects were obtained for pairs of equiluminant gratings (e.g. magenta/cyan vs purple/greenish-yellow) and pairs of equiluminant and luminant gratings (e.g. magenta/cyan vs dark-grey/light-grey, or purple/greenish-yellow vs dark-grey/light-grey). Maximum aftereffects occurred for gratings whose colours were modulated along the principle axes of the colour space of Krauskopf, Williams and Heeley (1982): an axis of short-wavelength cone activation (B-cone axis), the difference between long- and medium-wavelength cone activation (R-G cone axis), and an axis of a contrast ratio of long-, medium- and short-wavelength cone activation (R + G + B cone axis). The results indicate that selectivity for orientation occurs independently in at least two chromatic channels and one achromatic channel.
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During a period of 14 months in 1985 and 1986, infection with Mycobacterium avium-intracellulare (MAI) complex was diagnosed in 10 of 76 patients with Human Immunodeficiency Virus (HIV)-associated infection. In eight of the 10 patients, the infection was disseminated. All eight patients were anaemic. A bone marrow aspirate and/or trephine biopsy performed in six of them revealed evidence of red cell hypoplasia. MAI was cultured from all six samples of bone marrow. The strains of MAI isolated were resistant to conventional antituberculous drugs but were susceptible in vitro to ansamycin, ethionamide and cycloserine. None of the eight patients responded clinically to antituberculous therapy. The eight anaemic patients had pronounced constitutional symptoms. We suggest that severe anaemia and constitutional symptoms in patients with HIV-associated disease should prompt a search for evidence of disseminated MAI infection.
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Two conditioning regimens for bone marrow transplantation for patients with acute lymphoblastic leukaemia were compared. Both regimens (VVRAPID and VVRAPID-X) incorporated the same cytotoxic chemotherapy but differed in the radiation dose; VVRAPID employed a single fraction of 10.5 Gy and VVRAPID-X employed 10.5 Gy followed 4 days later by a further dose of 2.5 Gy. The 13-Gy split-fraction schedule was well tolerated with no significant increase in infection or requirement for blood products. An increase in gastrointestinal toxicity occurred but responded to increased oral anti-diarrhoeal agents. Overall survival and relapse rates did not differ significantly between the two groups. There was a trend for the 13-Gy schedule to reduce the graft failure rate following T cell-depleted bone marrow transplants.
The Tn3 resolvase requires that the two recombination (res) sites be aligned as direct repeats on the same molecule for efficient recombination to occur. To test whether resolvase must contact the DNA between res sites as predicted by tracking models, we have determined the sensitivity of recombination to protein diffusion blockades. Recombination between two res sites is unaffected either by lac repressor or bacteriophage T7 RNA polymerase being bound between them. Yet recombination is inhibited by lac repressor if the res site is bounded by a lac operator on both sides. We demonstrate that lac repressor will bind to more than one DNA site under the conditions used to assay recombination. This result suggests that lac repressor can inhibit resolvase by forming a DNA loop that isolates a res site topologically. These results do not support a tracking model for resolvase but suggest that the structure and topology of the DNA substrate is important in the formation of a synapse between res sites.
The Cell-Dyn 1000 is a new eight parameter fully automatic cell counter. This was evaluated following the ICSH guidelines. Scientific evaluation was generally satisfactory, largely conforming to the manufacturer's specifications. A number of potential microbiological safety hazards were noted; many could be overcome by minor modifications. Throughput and start-up/close-down times were acceptable. However, the reliability of the tested machine was felt to be less than satisfactory although this may be corrected by further minor machine modifications.
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