Parvovirus B19 infection and Diamond-Blackfan anaemia

It is the purpose of the study to report the frequency of parvovirus in children with a diagnosis of Diamond-Blackfan anaemia and to discuss the possible aetiological role of parvovirus in Diamond-Blackfan anaemia. We found parvovirus DNA in 3 of 11 bone marrow smears. Giant pronormoblasts showed low sensitivity (33%) and poor specificity (75%). The presence of giant pronormoblasts was associated with a very high myeloid: erythroid ratio, and may not be specific for parvovirus infection, but a feature of severely suppressed erythropoiesis. The three parvovirus-positive patients were the only children who experienced a remission, and who are free of medication. The seven surviving parvovirus-negative patients are all currently on steroid treatment.     

Protein restriction in chronic renal failure

The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1 g/kg/day) or the control group. All children were followed up by the same paediatrician and dietitian. After a follow up period of three years there was no significant difference in glomerular filtration rate between children on a protein restricted diet and children of the control group. There was no significant difference in weight with respect to height and height SD score between the protein restricted and the control group. Compliance with the protein restricted diet, as indicated by the prospective diet diaries and the serum urea:creatinine ratio, was good. This study shows that children with chronic renal failure do not benefit from a protein restricted diet.     

Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels

BACKGROUND AND PURPOSE

Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K⁺ (mitoK_ATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca²⁺ homeostasis during PPC, particularly changes in Ca²⁺ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca²⁺ channels.

EXPERIMENTAL APPROACH

PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca²⁺ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the α_1c subunit of L-type channels in the cellular membrane were measured by Western blot.

KEY RESULTS

PPC was accompanied by a 50% reduction in α_1c subunit levels, and by a reversible fall in L-type current amplitude and Ca²⁺ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoK_ATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the α_1c subunit and Ca²⁺ channel function were prevented in part by the protease inhibitor leupeptin.

CONCLUSIONS AND IMPLICATIONS

PPC downregulated the α_1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca²⁺ channel, which in turn reduced Ca²⁺ influx, which may attenuate Ca²⁺ overload during reperfusion.     

Collection of pluripotential hematopoietic stem cells by cytapheresis

Successful complete hematopoietic reconstitution (CHR) using nonleukemic peripheral stem cells (PSC) after marrow ablation has been reported in animals but not man. Previous studies of cytapheresis products from humans, as a prelude to use for CHR, have documented the presence of committed myeloid (CFU-GM) and erythroid (BFU-E) precursors. We have examined mononuclear cell (MNC) products collected on the Fenwal CS3000 Blood Cell Separator for these plus the more primitive mixed (granulo-, erythro-, mono-, and megakaryocytic) cell colony-forming units (CFU-GEMM) and for various lymphocytic subpopulations (LSP). One to two-hour products contained 36 +/- 7 CFU- GEMM/10(6) MNC (mean +/- SE, n = 8) or 490 +/- 131/ml product. This compared favorably with blood (23 +/- .4/10(6) MNC or 46 +/- 8/ml, n = 14) and bone marrow (146 +/- 58/10(6) MNC, n = 12). Collection efficiency for E-rosette-positive cells approximated that for total lymphocytes and was variable for other LSP. Recovery of CFU-GEMM after freezing in 10% dimethylsulfoxide at a controlled rate and storage in liquid N2 was 54% +/- 8% (n = 8). Cytapheresis collection of large numbers of pluripotent hematopoietic precursors and demonstration of adequate recovery of these after cryopreservation, both previously unreported, are significant steps toward eventual CHR using nonleukemic PSC.     

Life Satisfaction and Subsequent Physical,Behavioral, and Psychosocial Health in Older Adults

Policy Points

• Several intergovernmental organizations (Organisation for Economic Co‐operation and Development, World Health Organization, United Nations) are urging countries to use well‐being indicators (e.g., life satisfaction) in addition to traditional economic indicators when making important policy decisions.
• As the number of governments implementing this new approach grows, so does the need to continue evaluating the health and well‐being outcomes we might observe from policies aimed at improving life satisfaction.
• The results of this study suggest that life satisfaction is a valuable target for policies aiming to enhance several indicators of psychosocial well‐being, health behaviors, and physical health outcomes.

ContextSeveral intergovernmental organizations (Organisation for Economic Co‐operation and Development, World Health Organization, United Nations) are urging countries to use well‐being indicators (e.g., life satisfaction) in addition to traditional economic indicators when making important policy decisions. As the number of governments implementing this new approach grows, so does the need to continue evaluating the health and well‐being outcomes we might observe from policies aimed at improving life satisfaction.MethodsWe evaluated whether positive change in life satisfaction (between t₀;2006/2008 and t₁;2010/2012) was associated with better outcomes on 35 indicators of physical, behavioral, and psychosocial health and well‐being (in t₂;2014/2016). Data were from 12,998 participants in the University of Michigan''s Health and Retirement Study—a prospective and nationally representative cohort of US adults over age 50.FindingsParticipants with the highest (versus lowest) life satisfaction had better subsequent outcomes on some physical health indicators (lower risk of pain, physical functioning limitations, and mortality; lower number of chronic conditions; and higher self‐rated health) and health behaviors (lower risk of sleep problems and more frequent physical activity), and nearly all psychosocial indicators (higher positive affect, optimism, purpose in life, mastery, health mastery, financial mastery, and likelihood of living with spouse/partner; and lower depression, depressive symptoms, hopelessness, negative affect, perceived constraints, and loneliness) over the 4‐year follow‐up period. However, life satisfaction was not subsequently associated with many specific health conditions (i.e., diabetes, hypertension, stroke, cancer, heart disease, lung disease, arthritis, overweight/obesity, or cognitive impairment), other health behaviors (i.e., binge drinking or smoking), or frequency of contact with children, family, or friends.ConclusionsThese results suggest that life satisfaction is a valuable target for policies aiming to enhance several indicators of psychosocial well‐being, health behaviors, and physical health outcomes.     

Erythropoietin production by the fetal liver in an adult environment

To gain insight into the mammalian liver to kidney erythropoietin (Ep) switch, we heterotopically transplanted livers from preswitch, switched, and postswitch fetal and newborn lambs into normal adult sheep. Recipients' serum Ep and circulating reticulocyte levels were serially determined until rejection of the graft and compared with identical samples from sham-operated control adult ewes. Transplantation of preswitch and switched fetal livers caused an impressive rise in recipients' serum Ep activity and provoked a corresponding increase in reticulocytosis. In contrast, Ep activity and reticulocyte counts did not change from preoperative levels in adult ewes transplanted with postswitch livers or in the sham-operated controls. The production of Ep by the preswitch fetal liver in the adult environment was not dependent on the presence or absence of host kidneys and was stimulated by anemic hypoxia. These results suggest that the fetal liver is capable of producing relatively large amounts of Ep activity, and the production of Ep can be maintained in the adult environment in the presence of functional adult kidneys. This argues against suppression of liver Ep production by renal Ep, or some other factor in the postnatal environment, and suggests that the liver to kidney switch of Ep production during ontogeny may represent a genetically determined event.     

The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis [see comments]

The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG- CSF in normal granulocyte donors are warranted.