Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

The value of a pantaloon cast test in surgical decision making for chronic low back pain patients: a systematic review of the literature supplemented with a prospective cohort study

The results of lumbar fusion in chronic low back pain (LBP) patients vary considerably, and there is a need for proper patient selection. Lumbosacral orthoses have been widely used to predict outcome, however, with little scientific support. The aim of the present study was to determine the value of a pantaloon cast test in selecting chronic LBP patients for lumbar fusion or conservative management. First, a systematic review of the literature was carried out in which two independent reviewers identified studies in Medline, Cochrane and Current Contents databases. Three papers met the selection criteria. In the only study with a control group, a significantly better outcome after fusion compared to conservative treatment was found in patients who reported significant pain relief while in a cast (i.e. a positive cast test). The results of lumbar fusion, however, were not significantly different for patients with a positive and those with a negative cast test. In addition to the review, a clinical cohort study of 257 LBP patients, who had been allocated to either lumbar fusion or conservative management by a temporary external transpedicular fixation trial, was performed. Prior to allocation, all had undergone a pantaloon cast test. Patients with no history of prior spine surgery and with a positive pantaloon cast test had a better outcome after lumbar fusion than those treated conservatively (P = 0.002, χ ² test). In patients with previous spine operations the outcomes were poor and the test was of no value. From the literature and the present patient cohort, it was concluded that only in chronic LBP patients without prior spine surgery, a pantaloon cast test with substantial pain relief suggests a favorable outcome of lumbar fusion compared to conservative management. The test has no value in patients who have had previous spine surgery.     

Nodular lymphocyte-predominant Hodgkin’s lymphoma

Lymphocyte-predominant Hodgkin’s lymphoma (LPHL) differs in histologic and clinical presentation from classical Hodgkin’s lymphoma (cHL). Treatment of LPHL patients using standard Hodgkin’s lymphoma protocols leads to complete remission in more than 95% of patients. Survival and freedom from treatment failure are substantially worse in advanced-stage patients than for early-stage patients. Thus, patients in advanced stages and those in early stages with unfavorable risk factors should be treated similar to those with cHL. In contrast, patients with early-stage LPHL without risk factors might be sufficiently treated with reduced-intensity programs having less severe adverse effects. As a result, treatment of early LPHL is rather heterogeneous, including radiotherapy using extended-fleld technique, involved-fleld radiotherapy (IF-RT), combined-modality treatment, and, more recently, monoclonal antibodies. Watch-and-wait strategy plays an important role in pediatric oncology, to avoid adverse effects associated with therapy. IF-RT seems to be emerging as a treatment of choice for patients with stage IA LPHL; most larger study groups, such as the German Hodgkin Study Group and the European Organisation for Research and Treatment of Cancer, have adopted IF-RT as the treatment of choice for these patients.     

Modern wound dressings: Making and properties. II. Wound dressings containing immobilized proteolytic enzymes (a review)

Published data devoted to making and characterization of the properties of polymeric wound dressings with proteolytic action are reviewed. These data are indicative of individual dependence of the physicochemical properties, activity, and stability of each particular enzyme on the type of polymer matrix and the method of immobilization. In order to obtain wound dressings, which are active in physiological medium and retain their activity upon sterilization, it is necessary to optimize the composition and characteristics of a polymer matrix and the enzyme included into its structure. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 8, pp. 24–28, August, 2006.     

A Survey of Plants Used as Wild Vegetables in Four Districts of Botswana

A survey of plants used as wild vegetables was conducted in four districts of Botswana in August and September 2005. The objective was to determine which wild plants were used as vegetables in the study area, and to document their cooking and preservation methods. Fourteen species representing seven families were mentioned as wild vegetables. In addition, six species from four families had other uses in traditional medicine. The implications of the documented processing methods on the retention of nutrients in the vegetables are discussed.     

BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry.

In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-) (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-Abl specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph(+) CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant Ph(+) cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells.     

Quantifying physical activity in daily life with questionnaires and motion sensors in COPD.

Accurate assessment of the amount and intensity of physical activity in daily life is considered very important due to the close relationship between physical activity level, health, disability and mortality. For this reason, assessment of physical activity in daily life has gained interest in recent years, especially in sedentary populations, such as patients with chronic obstructive pulmonary disease (COPD). The present article aims to compare and discuss the two kinds of instruments more commonly used to quantify the amount of physical activity performed by COPD patients in daily life: subjective methods (questionnaires, diaries) and motion sensors (electronic or mechanical methods). Their characteristics are summarised and evidence of their validity, reliability and sensitivity is discussed, when available. Subjective methods have practical value mainly in providing the patients' view on their performance in activities of daily living and functional status. However, care must be taken when using subjective methods to accurately quantify the amount of daily physical activity performed. More accurate information is likely to be available with motion sensors rather than questionnaires. The selection of which motion sensor to use for quantification of physical activity in daily life should depend mainly on the purpose of its use.     

Anxiety in medically III patients

Anxiety disorders and anxiety symptoms are highly prevalent in the general population and more so in the medically ill. They have a number of negative consequences for these patients and may worsen the outcome of the medical illness and increase health care utilization. In the evaluation of these patients, it is of paramount importance to identify the etiology of the anxiety and, in particular, to differentiate primary from secondary anxiety. Management includes medications (especially benzodiazepines and selective serotonin reuptake inhibitors) and psychotherapy (particularly cognitive-behavioral therapy).