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Biomedical subjects

L Bindslev

Publications and source records attributed to L Bindslev.

At least 19 recordsLinked to original sources
PubMed2006

Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation.

PURPOSE: Stem cell therapy seems to be a new treatment option within cardiac diseases to improve myocardial perfusion and function. However, the delivery and traceability of the cells represent a problem. Radioactive labelling with 111In could be a method for tracking mesenchymal stem cells (MSCs). However, 111In could influence the viability and differentiation capacity of MSCs, which would limit its use. Therefore, the aim of this study was to evaluate the influence of 111In labelling in doses relevant for SPECT imaging in humans on the viability and differentiation capacity of human MSCs. METHODS AND RESULTS: Human MSCs isolated from bone marrow were incubated with 111In-tropolone (15-800 Bq/cell). The labelling efficiency was approximately 25% with 30 Bq/cell 111In. The MSC doubling time was 1.04+/-0.1 days and was not influenced by 111In within the range 15-260 Bq/cell. Using 30 Bq 111In/cell it was possible to label MSCs to a level relevant for clinical scintigraphic use. With this dose, 111In had no effect on characteristic surface and intracellular markers of cultured MSCs analysed both by flow cytometry and by real-time polymerase chain reaction. Further, the labelled MSCs differentiated towards endothelial cells and formed vascular structures. CONCLUSION: It is possible to label human MSCs with 111In for scintigraphic tracking of stem cells delivered to the heart in clinical trials without affecting the viability and differentiation capacity of the MSCs. This creates an important tool for the control of stem cell delivery and dose response in clinical cardiovascular trials.

Cell Differentiation↗
PubMed2005

Changes in circulating mesenchymal stem cells, stem cell homing factor, and vascular growth factors in patients with acute ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVE: To investigate the spontaneous occurrence of circulating mesenchymal stem cells (MSC) and angiogenic factors in patients with ST elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). DESIGN: In 20 patients with STEMI, blood samples were obtained on days 1, 3, 7, 14, 21, and 28 after the acute PCI. Fifteen patients with a normal coronary angiography formed a control group. MSC (CD45-/CD34-), plasma stromal derived factor 1 (SDF-1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2) were measured by multiparametric flow cytometry and enzyme linked immunosorbent assay (ELISA). RESULTS: Circulating CD45-/CD34- cells were significantly decreased on day 7 compared with day 3. Cell counts normalised one month after the acute onset of STEMI. The changes were mainly seen in patients with a large infarction. Plasma SDF-1 increased significantly from day 3 to day 28, and VEGF-A and FGF-2 increased significantly from day 7 to day 28. CONCLUSIONS: Spontaneous sequential fluctuations in MSC and the increase in vascular growth factor concentrations after STEMI suggest that the optimal time for additional stem cell therapy is three weeks after a myocardial infarction to obtain the maximum effects by stimulating endogenous growth factors on the delivered stem cells.

Angioplasty, Balloon, Coronary↗
PubMed2001

Risk factors for nosocomial intensive care infection: a long-term prospective analysis.

BACKGROUND: To identify risk factors for nosocomial infection in intensive care and to provide a basis for allocation of resources. METHODS: Long-term prospective incidence study of risk factors for nosocomial infection in the surgical-medical intensive care unit of a university hospital. RESULTS: A total of 2671 patients were admitted during four years, and 562 of 574 patients staying >48 h were observed during 4921 patient days (median length of stay 5 days, range 2-114). Of these, 196 (34%) patients had 364 nosocomial infections after median 8-10 days, an infection rate of 14/100 admissions. Infection prolonged length of stay 8-9 days and doubled the risk of death. The infections were 17% blood stream, 26% pneumonias, 34% wound, 10% urinary tract and 13% other infections. The incidence of bloodstream infection declined significantly during the study years, from 12% to 5%. In multiple regression analysis, the important variables for infection were central venous catheter, mechanical ventilation, pleural drainage and trauma with open fractures. High age, immunosuppression and infection on admission did not influence the risk of acquiring infection. Trauma patients constituted 24% of the study population. Trauma with open fractures increased the risk of infection more than twice (P=0.003), mainly due to wound infections. CONCLUSION: Trauma cases, with open fractures, were the patients most at risk of infection, despite low disease severity scores. Resources to prevent nosocomial infection should be allocated to these patients.

Adolescent↗
PubMed2001

Complementation of the Magnaporthe grisea deltacpkA mutation by the Blumeria graminis PKA-c gene: functional genetic analysis of an obligate plant pathogen.

Obligate plant-pathogenic fungi have proved extremely difficult to characterize with molecular genetics because they cannot be cultured away from host plants and only can be manipulated experimentally in limited circumstances. Previously, in order to characterize signal transduction processes during infection-related development of the powdery mildew fungus Blumeria graminis (syn. Erysiphe graminis) f. sp. hordei, we described a gene similar to the catalytic subunit of cyclic AMP-dependent protein kinase A (here renamed Bka1). Functional characterization of this gene has been achieved by expression in a deltacpkA mutant of the nonobligate pathogen Magnaporthe grisea. This nonpathogenic M. grisea deltacpkA mutant displays delayed and incomplete appressorium development, suggesting a role for PKA-c in the signal transduction processes that control the maturation of infection cells. Transformation of the deltacpkA mutant with the mildew Bka1 open reading frame, controlled by the M. grisea MPG1 promoter, restored pathogenicity and appressorium maturation kinetics. The results provide, to our knowledge, the first functional genetic analysis of pathogenicity in an obligate pathogen and highlight the remarkable conservation of signaling components regulating infection-related development in pathogenic fungi.

Archaeal Proteins↗
PubMed2000

Evidence that the cAMP pathway controls emergence of both primary and appressorial germ tubes of barley powdery mildew.

Development of conidia of barley powdery mildew involves the formation of a primary germ tube (PGT), an appressorial germ tube (AGT), and an appressorium. Previously, it was found that cyclic AMP (cAMP) was involved in these developmental processes. Comparison of development on the host surface with two types of cellulose membrane revealed that frequency of PGT emergence was surface independent. On one type of cellulose, where the frequencies of both AGT and appressorial differentiation were similar to that on the host surface, cAMP levels and protein kinase A (PKA) activities had a biphasic pattern with peaks at 15 min and 4 h after inoculation (prior to PGT and AGT emergence, respectively). The effect of manipulating cAMP levels was tested on another type of cellulose membrane, which stimulated a lower degree of AGT and appressorial formation than the host surface. Cholera toxin and forskolin, activators of adenylyl cyclase, significantly increased PGT emergence, but cAMP did not. Cholera toxin, forskolin, and cAMP increased the frequency of AGT and appressorial formation, but in a time-dependent manner.

Cellulose↗
PubMed1999

Involvement of cAMP and protein kinase A in conidial differentiation by Erysiphe graminis f. sp. hordei.

Erysiphe graminis f. sp. hordei, the causal agent of barley powdery mildew, is an obligate biotroph. On arrival on the host, a primary germ tube (PGT) emerges from the conidium. An appressorial germ tube (AGT) then appears, forms an appressorium, and effects host penetration. Such developmental precision may be due to multiple, plant-derived signals and to endogenous tactile and chemical signals. The transduction mechanism remains obscure. The isolation of an expressed sequence tag (EST) homologue of the catalytic subunit of cyclic AMP (cAMP)-dependent protein kinase A (PKA) enabled the corresponding gene to be characterized and the transcript to be identified in conidia and in PGT and AGT stage spores. cAMP-dependent PKA activity was detected in ungerminated conidia. These data suggest that PKA and cAMP are involved in conidial development. To substantiate this we exploited the responses of developing conidia to various surfaces, including exposure to the host leaf (fully inductive to AGT formation), cellulose membrane (semi-inductive), and glass (non-inductive). Assessment of fungal development, following application of exogenous cAMP or cAMP analogues, revealed that, at different concentrations and on different surfaces, cAMP either promoted or inhibited conidial differentiation. Various PKA inhibitors were tested for their effect on PKA activity and conidial development. A negative correlation was established between PKA inhibition in vitro and fungal development in vivo. Taken collectively, these data suggest that PKA and cAMP play a role in conidial differentiation in this obligate, plant-pathogenic fungus.

Amino Acid Sequence↗
PubMed1998

Individual lung blood flow during unilateral hypoxia: effects of inhaled nitric oxide.

We hypothesized that the diversion of blood away from a hypoxic lung to the opposite oxygenated lung can be enhanced by inhaling nitric oxide (NO) into the oxygenated lung. We measured individual lung blood flow when 50 ppm NO was selectively inhaled to: a hyperoxic lung during contralateral hypoxia; a normoxic lung during bilateral normoxia; and a hyperoxic lung during bilateral hyperoxia. Twenty two patients with healthy lungs were studied during intravenous anaesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas elimination technique. Unilateral hypoxic (inspiratory oxygen fraction (FI,O2) 0.05) ventilation during contralateral hyperoxia reduced the perfusion of the hypoxic lung from a mean (SD) of 47 (9)% of cardiac output (Q'), to 30 (7)% (p<0.001) of Q'. NO inhalation to the hyperoxic lung increased its blood flow from 70 (7)% to 75 (6)% (p<0.05) of Q', and reduced the blood flow to the hypoxic lung to 25 (6)% (p<0.05). Unilateral NO inhalation during bilateral normoxia or hyperoxia had no effect on pulmonary blood flow distribution. Nitric oxide inhalation to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow if the opposite lung is hypoxic.

Administration, Inhalation↗
PubMed1997

Hypoxic pulmonary vasoconstriction in human lungs. A stimulus-response study.

BACKGROUND: A stimulus-response relation between alveolar oxygen tension and pulmonary vascular resistance has been observed in animals. This study investigated this relation in healthy human lungs. The distribution of pulmonary blood flow was measured during unilateral (1) graded hypoxia (fractional concentration of oxygen in inspired gas [FIO2] = 0.12, 0.08, and 0.05) and contralateral hyperoxia (FIO2 = 1.0; n = 6); (2) single-step hypoxia (FIO2 = 0.05) and contralateral hyperoxia (n = 5); and (3) normobaric hyperoxia and contralateral normoxia (FIO2 = 0.25; n = 6). METHODS: Seventeen patients with healthy lungs were studied during intravenous anesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas (sulfurhexafluoride) elimination technique. RESULTS: (1) Unilateral graded hypoxia reduced the perfusion of the hypoxic lung from a mean (+/-SD) of 52 (2)% of cardiac output (Q) during bilateral hyperoxia, to 47 (5)% (P > 0.05) 40 (3)% (P < 0.01), and 30 (8)% (P < 0.001) of Q, respectively. These progressive reductions in the perfusion of the hypoxic lung were all significantly different from each other. (2) Unilateral single-step hypoxia caused a blood flow diversion of the same magnitude as when the lung was previously ventilated with FiO2 of 0.12 and 0.08. The perfusion of the hypoxic lung was reduced from 46 (9)% of Q (bilateral hyperoxia) to 26 (4)% of Q (P < 0.01). (3) Unilateral hyperoxia did not significantly change the relative blood flow distribution between the two lungs or the pulmonary artery pressure. CONCLUSIONS: A stimulus-response relation between graded hypoxia and blood flow diversion defines hypoxic pulmonary vasoconstriction in the normal human lung. Hyperoxia has no significant effect on vascular resistance in the normal human lung.

Adolescent↗
PubMed1997

A retrospective analysis of nitric oxide inhalation in patients with severe acute lung injury in Sweden and Norway 1991-1994.

BACKGROUND: Patients with severe acute lung injury (ALI) have been treated compassionately on doctors' initiative with inhaled nitric oxide (INO) in Sweden and Norway since 1991. In 1994 the previously used technical grade nitric oxide was replaced by medical grade nitric oxide. METHODS: We have carried out a retrospective data collection on all identified adult patients treated with INO for >4 h during the period 1991-1994 focusing on safety aspects and patient outcome. We used the following exclusion criteria (1) Age <18 years, (2) Simultaneous treatment with extracorporeal removal of CO2 (3) NO inhalation period <4 h, (4) Incomplete or missing patient charts, (5) Use of INO in order to treat pulmonary hypertension following cardiac surgery, with little or no acute lung injury. RESULTS: Inclusion criteria were met by 56 out of 73 identified patients. Mean age was 48+/-19 years and the median duration of INO treatment was 102 h. PaO2/FIO2 ratio at start of treatment was 85 +/- 33 mm Hg with a lung injury score (LIS) of 3.2+/-0.8. The aetiology of the lung injury was pneumonia (n= 27), sepsis (n=12) and trauma (n=8). Survival to hospital discharge was 41% and survival after 180 d was 38%. Three serious adverse events were identified, two from technical failures of the INO delivery device and one withdrawal reaction necessitating slow weaning from INO. No methaemoglobin values >5% were reported during treatment. CONCLUSION: The overall mortality did not differ dramatically from historical controls with high mortality. Only a randomised study may determine whether INO as an adjunct to treatment alters the outcome in severe ALI. One cannot at present advocate the routine use of INO in patients with ALI outside such studies.

Administration, Inhalation↗
PubMed1996

Surface heparinization of central venous catheters reduces microbial colonization in vitro and in vivo: results from a prospective, randomized trial.

OBJECTIVE: To evaluate in vitro and in vivo the efficacy of covalent end point-attached heparin to single-lumen polyurethane central venous catheters in reducing microbial adherence and colonization. DESIGN: In vitro study: A controlled bench study. In vivo study: A prospective, randomized, double-blind, clinical trial. SETTING: Intensive care unit in a 1200-bed teaching hospital. INTERVENTIONS: In vitro study: Adhesion of 17 radiolabeled clinical isolates of Staphylococci to catheters was examined in vitro. In vivo study: The outcome of heparinized and control catheters was compared in vivo in patients receiving long-term parenteral nutrition. Fifty-five adult patients were prospectively, blindly randomized to heparinized or control central venous catheters. The catheters, removed on clinical grounds, were analyzed with semiquantitative and quantitative cultures. Blood cultures were done at catheter removal. MEASUREMENTS AND MAIN RESULTS: In vitro study: Coagulase-negative Staphylococci adhered less in vitro to heparinized catheters than to control catheters (p < .05). In vivo study: Among 32 central venous catheters, or patients who completed the study, catheter-associated bacteremia or fungemia was observed in five patients in the control group (n = 19) and in no patient with a heparinized catheter (n = 13) (p = .047). Four of 13 catheters in the heparin group were colonized compared with 14 of 19 in the control group (p = .03). Coagulase-negative Staphylococci were the most frequent microorganisms in both groups. The numbers of organisms found on colonized catheters were larger in the control group than in the heparin group. CONCLUSIONS: Covalent end point surface heparinization appears to have a great impact on both in vitro and in vivo bacterial colonization of central venous catheters. Such heparinization can be a practical and economical approach to the prevention of catheter-associated bacteremia or fungemia.

Adult↗
PubMed1991

Extracorporeal carbon dioxide removal performed with surface-heparinized equipment in patients with ARDS.

To avoid the drawbacks of systemic anticoagulation during prolonged extracorporeal circulation in patients with adult respiratory distress syndrome (ARDS) a heparinization technique has been developed by which partially degraded heparin can be covalently end-point attached to the surface of the equipment constituting the extracorporeal circuit (Carmeda Bio-Active Surface, CBAS) thereby localizing the anticoagulatory effect. Since 1986 we have used extracorporeal circuits and membrane lungs coated with the CBAS for extracorporeal lung assistance (ECLA) in 14 patients suffering from ARDS. The patients were on ECLA for 3 to 55 days with a survival rate of 43%. Our experience so far is that by using equipment coated with CBAS it is possible to perform long-term extracorporeal circulation with a minimum of intravenously administered heparin, thus avoiding the risk of major coagulation defects.

Adult↗
PubMed1987

Hypoxia-induced pulmonary vasoconstriction in the human lung. The effect of isoflurane anesthesia.

The influence of isoflurane on hypoxic pulmonary vasoconstriction (HPV) was studied in eight subjects prior to elective surgery. The lungs were ventilated separately with a double-lumen endobronchial catheter. After oxygen ventilation of both lungs for 30 min during intravenous barbiturate anesthesia, the test lung was rendered hypoxic by ventilation with 8% O2 in nitrogen. The control lung was ventilated continuously with 100% O2. Isoflurane was added to the inspired gas, so that end-tidal concentrations of 1% and 1.5% were obtained. Cardiac output (QT) was determined by thermodilution, and the distribution of blood flow between the lungs was assessed from the excretion of a continuously infused, poorly soluble gas (SF6). The hypoxic challenge during intravenous anesthesia resulted in a reduction in the fractional perfusion of the test lung from 54% to 41% of QT. Mean pulmonary arterial pressure increased by 46%, and pulmonary vascular resistance (PVR) of the test lung more than doubled. Arterial oxygen tension fell from 375 mmHg (50 kPa) to 101 mmHg (13.5 kPa). Adding isoflurane to the inhalation gas, first at a concentration of 1%, then 1.5%, caused no further significant change in the distribution of pulmonary blood flow, although six of the eight subjects showed a small increase in test lung blood flow at isoflurane 1.5%. There was no change in PVR or in any other circulatory variable. Arterial blood gases remained essentially unaltered. When the hypoxic challenge was discontinued, all variables returned to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗