In vitro assessment of motility and proliferation of human osteogenic cells on different isolated extracellular matrix components compared with enamel matrix derivative by continuous single-cell observation

OBJECTIVES: The composition of the extracellular matrix (ECM) plays a substantial role in bone remodelling, fracture healing and osseointegration of dental implants by regulating proliferation, migration and finally differentiation of osteogenic cell populations. Emdogain, a composition of an enamel matrix derivative (EMD), has been introduced as a potential candidate to promote tissue regeneration. We investigated whether EMD could serve as a potential promoter of cell proliferation and motility as a dynamic cell response and compared the results with the ubiquitous single ECM components type I collagen and laminin. MATERIAL AND METHODS: In the investigation presented, we used a continuous observation method for the analysis of migratory and proliferative patterns of individual cells. We analyzed the response of four osteoblastic cell lines to specific extracellular ligands (type I collagen, laminin and EMD) over a period of 24 h compared with untreated glass surface and bovine serum albumin (BSA) as control groups. RESULTS: Type I collagen and laminin promoted cell motility significantly compared with the control groups and, in part, compared with EMD as well. The analysis of all 451 investigated cells revealed the following mean values for cell motiliy: untreated glass (n=99): 5.46+/-2.74 microm/h, BSA (n=89): 6.35+/-2.43 microm/h, type I collagen (n=108): 8.77+/-3.42 microm/h, laminin (n=74): 9.89+/-5.10 microm/h and EMD (n=81): 7.92+/-3.35 microm/h. Proliferation rates on the different surfaces were heterogenous for all investigated cell lines and varied from 0% to 50% within 24 h without a correlation to cell motility. CONCLUSION: In our study, EMD promotes cell motility better than the control groups. The two investigated single ECM components type I collagen and laminin promoted cell motility superior to EMD. This supports the hypothesis that EMD promotes a less mobile but more differentiated osteogenic phenotype.     

Postautologous stem cell transplantation engraftment syndrome: Improved treatment and outcomes

Postautologous stem cell transplantation (ASCT) engraftment syndrome (ES) is a well-known clinical complication; however, many aspects remain largely controversial. In this retrospective study, we reviewed records of 156 ASCTs done over 2 years in our institution. Our results show that 45 (34 multiple myeloma/amyloidosis and 11 lymphoma) of 156 adult patients (29%) were diagnosed with ES. Patients with ES were significantly more likely to have fever, rash, and diarrhea upon engraftment. Risk factors for ES included shorter time from diagnosis to ASCT (P = .029), and lower number of pretransplant treatment regimens (0.012). Post-ASCT, patients with ES had significantly lower absolute lymphocyte count on first engraftment day (P = .014). Most ES patients received treatment with steroids. Initial dose of prednisone/methylprednisolone was 2 mg/kg (n = 34), 1 mg/kg (n = 7), while four patients received 1000 mg IV with median length of therapy 7.5 days. One ES patient with inadequate steroid therapy died of ES complications, while another developed respiratory failure requiring intubation but had full recovery with steroids treatment. In conclusion, patients with shorter time from diagnosis to ASCT and with less prior therapy are more likely to develop ES. Overall survival of ES patients has improved with greater awareness of the diagnosis and earlier use of steroids.     

Male Inmate Profiles and Their Biological Correlates

Objective:

Borderline and antisocial personality disorders (PDs) share common clinical features (impulsivity, aggressiveness, substance use disorders [SUDs], and suicidal behaviours) that are greatly overrepresented in prison populations. These disorders have been associated biologically with testosterone and cortisol levels. However, the associations are ambiguous and the subject of controversy, perhaps because these heterogeneous disorders have been addressed as unitary constructs. A consideration of profiles of people, rather than of exclusive diagnoses, might yield clearer relationships.

Methods:

In our study, multiple correspondence analysis and cluster analysis were employed to identify subgroups among 545 newly convicted inmates. The groups were then compared in terms of clinical features and biological markers, including levels of cortisol, testosterone, estradiol, progesterone, and sulfoconjugated dehydroepiandrosterone (DHEA-S).

Results:

Four clusters with differing psychiatric, criminal, and biological profiles emerged. Clinically, one group had intermediate scores for each of the tested clinical features. Another group comprised people with little comorbidity. Two others displayed severe impulsivity, PD, and SUD. Biologically, cortisol levels were lowest in the last 2 groups and highest in the group with less comorbidity. In keeping with previous findings reported in the literature, testosterone was higher in a younger population with severe psychiatric symptoms. However, some apparently comparable behavioural outcomes were found to be related to distinct biological profiles. No differences were observed for estradiol, progesterone, or DHEA-S levels.

Conclusions:

The results not only confirm the importance of biological markers in the study of personality features but also demonstrate the need to consider the role of comorbidities and steroid coregulation.     

Relation between contractile reserve and prognosis in patients with coronary artery disease and a depressed ejection fraction.

Postextrasystolic potentiation (PESP) and 1-epinephrine infusion have previously been shown by the ventriculographic technique to augment left ventricular wall motion in patients with coronary artery disease. The present study relates the magnitude of this augmentation to short-term prognosis in 56 patients with coronary artery disease and a factor already identified with reduced life expectancy, i.e., an abnormal ejection fraction (EF less than .50). Forty-two patients received PESP and 14 1-epinephrine infusion. Based on severity of symptoms and technical suitability, 37 were treated surgically and 19 medically. Mean follwo-up times were 11.7 and 14.3 months, respectively. The mean increase in EF induced by PESP or 1-epinephrine infusion was significantly greater in patients who subsequently had good results from either surgical or medical therapy than in those who died or had progressive cardiac deterioration. In addition, those patients with an increase in EF of .10 or greater had a statistically greater chance of doing well than patients with less augmentation. Evaluation of change in ejection fraction after inotropic stimulation in patients with depressed ejection fractions is helpful in identifying those patients with greatest contractile reserve and hence better short-term prognosis with eigher medical or surgical therapy. Because of its ease of performance and greater enhancement of contractility, PESP is preferred to 1-epinephrine infusion as the inotropic stimulus of choice.     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Decomposition of a mixture of signals in a model of the olfactory bulb.

We describe models for the olfactory bulb which perform separation and decomposition of mixed odor inputs from different sources. The odors are unknown to the system; hence this is an analog and extension of the engineering problem of blind separation of signals. The separation process makes use of the different temporal fluctuations of the input odors which occur under natural conditions. We discuss two possibilities, one relying on a specific architecture connecting modules with the same sensory inputs and the other assuming that the modules (e.g., glomeruli) have different receptive fields in odor space. We compare the implications of these models for the testing of mixed odors from a single source.     

“I don’t need my patients’ opinion to withdraw treatment”: patient preferences at the end-of-life and physician attitudes towards advance directives in England and France

This paper presents the results of a qualitative interview study exploring English and French physicians’ moral perspectives and attitudes towards end-of-life decisions when patients lack capacity to make decisions for themselves. The paper aims to examine the importance physicians from different contexts accord to patient preferences and to explore the (potential) role of advance directives (ADs) in each context. The interviews focus on (1) problems that emerge when deciding to withdraw/-hold life-sustaining treatment from both conscious and unconscious patients; (2) decision-making procedures and the participation of proxies/relatives; (3) previous experience with ADs and views on their usefulness; and (4) perspectives on ways in which the decision-making processes in question might be improved. The analysis reveals differences in the way patient preferences are taken into consideration and shows how these differences influence the reasons physicians in each country invoke to justify their reluctance to adhering to ADs. Identifying cultural differences that complicate efforts to develop the practical implementation of ADs can help to inform national policies governing ADs and to better adapt them to practice.     

Bedeutung der Tumorstammzellhypothese für das Verständnis des Ovarialkarzinoms

Background

Despite complex surgical and systemic therapies epithelial ovarian cancer has a poor prognosis. A small quantity of tumorigenic cells termed cancer stem cells (CSC) are responsible for the development of chemoresistance and high rates of recurrence.

Objectives

This review presents the CSC hypothesis and describes methods of identification and enrichment of CSCs as well as approaches for the therapeutic use of these findings.

Material and methods

A systematic literature review based on PubMed and Web of Science was carried out.

Results

The CSC model is based on a hierarchical structure of tumors with few CSCs and variably differentiated tumor cells constituting the tumor bulk. Only the CSCs possess tumorigenic potential. Other essential functional characteristics of CSCs are their potential for self-renewal and their ability to differentiate into further cell types. The CSCs are structurally characterized by different surface markers and changes in certain signaling pathways. Currently there are phase I and II studies in progress investigating specific influences on CSCs.

Conclusion

Various clinical characteristics of the course of disease in ovarian cancer are aptly represented by the tumor stem cell model. In spite of precisely defined functional characteristics of CSCs, surface markers and signaling pathways show individual differences and vary between tumor entities. This complicates identification and enrichment. Current experimental findings in various approaches and even first clinical studies raise hopes for a personalized cancer therapy targeting CSCs.     

Prevention of indwelling central venous catheter sepsis

In an attempt to decrease the incidence of central venous catheter sepsis in children with cancer, we conducted a study to evaluate the benefit of adding broad-spectrum antibiotics to the catheter “flush solution.” In a prospective, placebo-controlled, double-blinded, randomized trial, 69 children with different types of malignancies were studied. The central venous catheters in these children were flushed with either the standard solution (normal saline + 100 U/ml of heparin) or the study solution (25 μg/ml of both amikacin and vancomycin added to the standard solution). At the conclusion of the study, 64 children with a total of 67 indwelling central venous lines were assessable. The total catheter days on study were 20,700 days, with a median of 323 catheter days per patient. We documented 10 events of catheter-related infections (0.49 events/1,000 catheter days at risk). Five of these events were catheter-related sepsis (0.24 sepses/1,000 catheter days): two were fungal and three were bacterial. Due to the low incidence of catheter-related sepsis in this study, no statement regarding the prophylactic use of antibiotics could be made. The extremely low rate of catheter-related sepsis reported herein may be retrospectively attributed to continuous staff education regarding aseptic techniques in handling these catheters. Staff education is essential, and probably the most effective factor in preventing catheter-related sepsis. © 1996 Wiley-Liss, Inc.