We have reviewed the management of pregnant women presenting with acute myeloblastic leukaemia (AML) at the London Hospital since 1972. Six women in the second or third trimester were diagnosed with ...AML over this period. One woman had termination of pregnancy at presentation in the second trimester. Three of the remaining five patients achieved complete remission following chemotherapy during pregnancy. Delivery was achieved by the vaginal route in three and by caesarean section in one patient. All were livebirths but one infant had Down's syndrome. Median maternal survival was 16 months (range 0-44 months). Long-term survival was achieved for both mother and infant in only one case. Longer maternal survival was seen in patients treated in the period 1980-1985. Increased survival appears to be related to the introduction of more aggressive chemotherapy schedules and improved supportive care.
This investigation compared the predictions of two models describing the integration of reinforcement and punishment effects in operant choice. Deluty's (1976) competitive‐suppression model ...(conceptually related to two‐factor punishment theories) and de Villiers' (1980) direct‐suppression model (conceptually related to one‐factor punishment theories) have been tested previously in nonhumans but not at the individual level in humans. Mouse clicking by college students was maintained in a two‐alternative concurrent schedule of variable‐interval money reinforcement. Punishment consisted of variable‐interval money losses. Experiment 1 verified that money loss was an effective punisher in this context. Experiment 2 consisted of qualitative model comparisons similar to those used in previous studies involving nonhumans. Following a no‐punishment baseline, punishment was superimposed upon both response alternatives. Under schedule values for which the direct‐suppression model, but not the competitive‐suppression model, predicted distinct shifts from baseline performance, or vice versa, 12 of 14 individual‐subject functions, generated by 7 subjects, supported the direct‐suppression model. When the punishment models were converted to the form of the generalized matching law, least‐squares linear regression fits for a direct‐suppression model were superior to those of a competitive‐suppression model for 6 of 7 subjects. In Experiment 3, a more thorough quantitative test of the modified models, fits for a direct‐suppression model were superior in 11 of 13 cases. These results correspond well to those of investigations conducted with nonhumans and provide the first individual‐subject evidence that a direct‐suppression model, evaluated both qualitatively and quantitatively, describes human punishment better than a competitive‐suppression model. We discuss implications for developing better punishment models and future investigations of punishment in human choice.
Objectives: To compare long‐term care (LTC) residents with and without multiple sclerosis (MS); to compare admission status of pain, physical disability, pressure ulcers, depression, and cognitive ...performance in LTC residents with and without MS; and to examine the impact of MS and pain on outcomes 90 and 180 days after LTC admission.
Design: Retrospective analysis of a large data set.
Setting: LTC facilities in Missouri.
Participants: Residents admitted to non‐hospital‐based LTC facilities.
Measurements: Minimum Data Set/Resident Assessment Instrument, Version 2.0; Activities of Daily Living Scale; Cognitive Performance Scale.
Results: Residents with and without MS had similar pain prevalence and intensity after admission, with daily pain more frequent in residents with MS (P=.03). On admission, residents with MS had more physical disability (P<.001) and a greater prevalence of pressure ulcers (P=.004) and depression (P<.001) than residents without MS. In all LTC residents, initial pain status was associated with physical disability (P<.001), pressure ulcers (P<.001), depression (P<.001), and cognitive performance (P<.001) 90 and 180 days after admission. A diagnosis of MS was associated with physical disability (P<.001) 90 and 180 days after admission and pressure ulcer development 180 days after admission (P=.02).
Conclusion: Residents with MS were more physically disabled and had more frequent pain and a higher prevalence of pressure ulcers and depression on admission than residents without MS. Pain, or lack thereof, in residents with and without MS on admission may warn of problems that could occur within 6 months after admission to a LTC facility.
Lactational exposure to mercury in experimental models Newland, M. Christopher; Paletz, Elliott M.; Reed, Miranda N.
Neurotoxicology (Park Forest South),
2009, 2009-1-00, 20090101, Letnik:
30, Številka:
1
Journal Article
Recenzirano
The extent to which there is methylmercury exposure via breast milk is important in animal models of human developmental exposures. The concentration of organic and inorganic mercury in breast milk ...reflects the concentration in plasma, from which milk derives. Accordingly, much mercury in milk is inorganic and poorly absorbed. The concentration of organic MeHg in milk is many times lower than that seen in blood. Because of these factors, lactational exposure is very small compared with prenatal exposure. In studies in which MeHg was present throughout gestation the near-weaning pups may have consumed mercury directly from the feed or water. Experimentalists should ensure that near-weanling rodents cannot consume MeHg directly.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), gamma interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) can regulate monocyte maturation and activation. Using the human ...monocytoid cell line U937, we have shown that these agents increase surface tumor necrosis factor (TNF) expression without directly affecting TNF release. GM-CSF and IFN-gamma combined with 1,25(OH)2D3 increased cellular TNF secretion to levels not seen with these agents alone. Ability to express and secrete TNF in part depended on degree of monocytic maturation. The combination of 1,25(OH)2D3 and GM-CSF, however, facilitated lipopolysaccharide (LPS)-mediated release of surface TNF from U937 cells, an effect that was temporally independent of maximal maturation. 1,25(OH)2D3 plus IFN-gamma was less effective than 1,25(OH)2D3 plus GM-CSF at facilitating TNF secretion. We postulate that 1,25(OH)2D3 and GM-CSF are required together to prime a specific mechanism, probably a protease, which cleaves TNF from the surface of monocytic cells. This protease, once primed, can be activated by a secondary stimulus such as LPS.
IntroductionNeonates with critical congenital heart disease (CHD) exhibit a high prevalence of white matter injury (WMI). Recent work in neonates with hypoplastic left heart syndrome has shown that a ...longer wait from birth to surgery was associated with lower cerebral tissue oxygen saturations (StO2) on the morning of surgery and an increased risk for postoperative white matter injury (WMI). Understanding the daily preoperative changes in cerebral physiology during this vulnerable period may lead to new therapeutic algorithms aimed at prevention of WMI.MethodsTerm neonates with critical CHD were recruited for this study. Frequency domain diffuse optical spectroscopy was employed to noninvasively quantify StO2. Daily StO2 measurements were made from day of recruitment until the day of surgery.ResultsWe studied 37 neonates with critical CHD. Operations were performed at 1-8 days of life. Non-elective reasons for timing of surgery resulted only in earlier surgery in this cohort. The subjects were placed in 2 groups depending on if they had a normal arch (N=20) or obstructed arch (N=17). In a linear mixed-effects model, StO2 decreased as a function of time from birth but was not specific to diagnostic group.ConclusionsObserved longitudinal daily decline in StO2 from birth until surgery supports our earlier findings and extends them to other groups of CHD. These results suggest that reported increases in risk for WMI with time-to-surgery could be due to mismatched oxygen delivery to metabolic demand. Therapeutic interventions such as increasing cerebral blood flow or decreasing cerebral oxygen demand may be considered when earlier surgery is not possible.
IntroductionWe have previously reported that earlier stage I palliation (S1P) is protective against White Matter Injury (WMI) for term infants with hypoplastic left heart syndrome (HLHS). The present ...study compares clinical outcomes from the acute hospitalization between neonates who had early (≤ 4 days) versus late surgery (> 4 days).HypothesisEarlier S1P intervention is associated with greater post-operative complications rates.MethodsA retrospective chart review was performed on all neonates with HLHS or variants who underwent S1P at a single institution between 10/2008 - 03/2013. Excluded were a preterm (<37 weeks gestation), left-ventricle physiology, prior operations and international referral. Anthropometric data, pre- post- and intra-operative factors, post-operative complications, and both intensive care unit (ICU) and hospital length of stay were evaluated for differences between early vs. late surgery. Analysis was performed excluding patients who had either early, or late surgery for non-elective diagnoses.ResultsA total of 145 infants, 114 (73 with early surgery, 41 late) met inclusion criteria. The mean day of surgery was 4.2 days (early 2.7±0.1 days, late 6.9±3.7 days). There were no significant differences between the groups’ post-operative complications or operative factors (see Table 1). In addition exclusion of patients with non-elective change to their surgical date did not change results significantly. Neonates who had earlier surgery had significantly longer post-operative ICU stay (median 9 days vs. median 13 days, p = 0.02).ConclusionEarly surgery for neonates with HLHS was not associated with either protection against or greater risk for post-operative complications. Neonates who have earlier surgery have a longer initial post-operative ICU stay, but total ICU and hospital stay was not different than that for infants with surgery after day four.
The monocytic U937 cell line, though immature, has many properties in common with mature monocytes. We have studied the antigenic expression and activity of tissue factor (TF) in the cytosol and on ...the surface of U937 cells after exposure to GM-CSF and endotoxin (LPS). Following exposure to LPS, both TF phenotype and procoagulant activity (PCA) increased linearly, with peak expression and activity after 18 hours of stimulation. Total PCA (tPCA) increased as early as 6 hours, unlike surface PCA (sPCA) which peaked at 18 hours. A linear correlation was observed between surface TF and both sPCA and tPCA. Incubation of cells with rHuGM-CSF did not effect phenotypic markers of monocyte maturation and had no significant effect on TF expression or PCA. However, cells activated with LPS after rHuGM-CSF priming, demonstrated accelerated expression of TF and PCA, with TF expression peaking at 6 hours and PCA at 2 hours. No increase in the absolute levels of TF were seen after priming with GM-CSF. We conclude that GM-CSF accelerates, but does not increase the magnitude of, the procoagulant response of monocytic cells to endotoxin. We propose that the initial accelerated PCA induction by LPS after rHu-GM-CSF priming, was due to conformational changes in TF and was not due to de novo synthesis of TF protein.
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