Excellent results of a femoral press-fit stem cemented with a thin mantle: 116 hips followed for 11–18 years

We report the outcome of a femoral stem designed for press-fit insertion and cemented with a thin mantle. During the years 1986–1992 we performed 346 primary total hip replacements in 305 patients. Their mean age at the time of the surgery was 75 (range, 52–91 years). During the follow-up, 206 patients had died (227 hips) and 3 were lost. This left us with 96 patients (116 hips), who were followed for a mean of 13 years (range, 11–18 years). Stem survivorship according to Kaplan–Meier analysis indicated a total survival of 0.982 (confidence intervals, 0.952–1). The mechanical survival rate was 0.985 (confidence intervals, 0.955–1) at 17 years with one patient at risk. Fifty-nine (70%) of the surviving patients were very satisfied with the operated hip, 22 (26%) were satisfied, 2 (2.5%) were content, and 1 (1.5%) was dissatisfied. Then, the press-fit stem allowing minimal cement has a 17-year survival rate of 0.98.     

Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy- induced leucopenia

Abstract: Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1α and IL1β caused a similar increase in AML blast release of IL1RA, and addition of anti-ILl antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor α (TNFα), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony- stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1β and soluble TNFα receptors increased when the leucopenic patients developed complicating bacterial infections.     

The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10

Sepsis caused by gram-positive bacteria lacking lipopolysaccharide (LPS) has become a major and increasing cause of mortality in intensive-care units. We have recently demonstrated that the gram-positive-specific bacterial cell wall component lipoteichoic acid (LTA) stimulates the release of the proinflammatory cytokines in Kupffer cells in culture. In the present study, we have started to assess the signal transduction events by which LTA induces the production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 in rat Kupffer cells. LTA was found to trigger phosphorylation of mitogen-activated protein kinases (MAPK) (p38 MAPK and ERK 1/2) and protein kinase B (PKB). Compared to LPS, LTA was more potent in inducing PKB phosphorylation after 40 min, although we found that the cytokine responses were similar. For both bacterial molecules, blocking phosphatidylinositol 3-kinase (PI3-K; Ly294002) or Janus kinase 2 (JAK-2; AG490) particularly affected the induction of IL-6 and IL-10 release, whereas TNF-alpha levels were strongly reduced by inhibition of Src family tyrosine kinases (PP2). All three cytokines were reduced by inhibition of p38 MAPK (SB202190) or the broad-range tyrosine kinase inhibitor genistein, whereas IL-6 release was particularly blocked by inhibition of ERK 1/2 (PD98059). Divergences in the regulatory pathways controlling TNF-alpha, IL-10, and IL-6 production in Kupffer cells following LPS or LTA stimulation may create a basis for understanding how the balance between pro- and anti-inflammatory cytokines is regulated in the liver following infections by gram-positive or gram-negative bacteria.     

Regulation of tissue-degrading factors and in vitro invasiveness in progression of breast cancer cells

Hormone-independent growth and invasiveness represent phenotypic properties acquired during early progression of breast cancer. We compared human mammary adenocarcinoma cells, MCF-7, which are estrogen-dependent and poorly metastatic, with the estrogen-independent and highly metastatic subline, MCF7/LCC1, with regard to expression of tissue-degrading factors of the matrix metalloproteinase (MMP)-and urokinase (uPA)-dependent degradative pathways, as well as for their in vitro invasive properties. Both cell lines showed low constitutive mRNA expression of the MMP inhibitor TIMP-1. Baseline expression of TIMP-2 mRNA was also very low in MCF-7 cells, whereas the MCF7/LCC1 level was much higher (~10- fold). Furthermore, both cell lines revealed low constitutive capacity to migrate in an in vitro invasion assay. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nM) induced the mRNAs for TIMP-1 as well as for MMP-1, MMP-9, the uPA receptor, and the uPA inhibitor PAI-1, am ongst which only the responses of MMP-9 and PAI-1 were cell-specific. The mRNA levels of MMP-9 and PAI-1 were ~10-fold and ~15-fold higher in MCF7/LCC1 cells compared to MCF-7 cells. The secretion of immuno-reactive PAI-1 was considerably elevated (. 20-fold) in TPA-treated MCF7/LCC1 cells, whereas the TPA-dependent level of 92-kDa MMP-9 was only ~2-fold higher in MCF7/LCC1 cells than in MCF-7 cells. In both cell lines treatment with TPA was associated with an increase (~10-fold) in in vitro migration, which in the MCF7/LCC1 cells was significantly attenuated by a reconstituted basement membrane extract (Matrigel). These data suggest that TPA-responsive in vitro invasive properties that are probably associ-ated with PAI-1 expression may co-vary with progression from hormone-dependent to -independent breast cancer. © Rapid Science 1998     

Flattening the quality of life curve? A prospective person-centred study from Norway amid COVID-19

Quality of Life Research - We examined multidimensional, heterogeneous reactions to the COVID-19 pandemic and associated measures to provide further insights into the developmental processes of...     

In vitro effect of r-verapamil on acute myelogenous leukemia blast cells: studies of cytokine secretion and cytokine-dependent blast proliferation

The in vitro effect of the dextroisomer r-verapamil on blast cells derived from patients with acute myelogenous leukemia (AML) was studied. R-verapamil caused a dose-dependent inhibition of AML blast proliferation in the presence of stem-cell factor, leukemia inhibitory factor, interleukin 4, interleukin 6, and interleukin 10 when these cytokines were tested both alone and in different combinations. R-verapamil also inhibited the growth of clonogenic AML blast cells. The antiproliferative effect was not specific for AML blast cells, because r-verapamil also inhibited cytokine-dependent proliferation of blast cells derived from patients with acute lymphoblastic leukemia. The inhibitory effects of r-verapamil and anti-IL1 serum were additive, suggesting that the antiproliferative effect of r-verapamil does not depend solely on inhibition of IL1-mediated effects. Although r-verapamil inhibited spontaneous AML blast proliferation, for a majority of patients it caused only minimal, if any, inhibition of spontaneous cytokine secretion (IL1, IL1, TNF, IL6) by AML blast cells. Thus, although inhibition of IL1 effects may contribute in certain patients to the antiproliferative effect of r-verapamil, mechanisms other than IL1 inhibition seem to be more important in mediating the effects of r-verapamil.Abbreviations ALL Acute lymphocytic leukemia - AML acute myelogenous leukemia - cpm counts per minute - ELISA enzyme-linked immunosorbent assay - G-CSF granulocyte colony-stimulating factor - GM-CSF granulocyte-macrophage colony-stimulating factor - IL interleukin - IF leukemia inhibitory factor - PBMC peripheral blood mononuclear cells - RR relative response - SCF stem cell factor - TNF tumor necrosis factor      

The prevalence of respiratory symptoms and asthma among school children in three different areas of Norway

The role of exposure to ambient air pollution has been a topic of interest as a potential risk factor for respiratory symptoms and asthma. We expected that the prevalence rates would vary in Norway between the capital, Oslo, the mountainous area Hallingdal and the industrial area Odda. Surveys were conducted in school children, aged 6-16 years, in; Oslo (n=2577), Hallingdal (n=1177) and Odda (n=831). The parent-reported prevalence of wheeze in past year was almost similar in Oslo (13. 1 (95% CI 11. 7-14. 5)) and Upper Hallingdal (14. 2 (13. 1–15. 3)), but lower in Odda (9. 0 (7. 0–11. 0)). The findings for severe respiratory symptoms were almost equal. The age patters within each area differed. The risk of wheeze ever (p < 0.001) and wheeze in past year (p=0.04) decreased with increasing age in Odda, while there was an increase in the risk of exercise induced wheeze in Oslo (p=0.02) and Hallingdal (p < 0.001). The lifetime prevalence of asthma was lowest in Odda (5. 4 (3. 8–7. 0)) compared to Oslo (9. 4 (8. 2–10. 6)) and Hallingdal (8. 5 (6. 8–10. 2)). There was a positive association between physical activity and wheeze in past year. The results do not support the hypothesis that respiratory morbidity is more common in urban than rural areas, age and physical activity can influence the prevalence rates of respiratory symptoms in school children.