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Biomedical subjects

U Martin

Publications and source records attributed to U Martin.

At least 55 records · Page 3Linked to original sources
PubMed2000

Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV).

The potential risk of viral transmission in the setting of xenotransplantation has gained major attention. Different porcine cell types have been shown to release retroviral particles, which are infectious for human cell lines in vitro. However, there are only a few data on whether PERV (pig endogenous retrovirus) is able to infect primary human cells. In this study we have analyzed endothelial cells, vascular fibroblasts, mesangial cells, mononuclear cells, hematopoetic stem cells and bone marrow stromal cells for PERV transmission. We now provide evidence for primary human endothelial cells, vascular fibroblasts, and mesangial cells to be susceptible to PERV transmission. PERV infection was productive in endothelial cells and mesangial cells. Our data confirm and extend former reports concerning the PERV infection of human cells. The PERV infection of different primary human cells represents further significant evidence for a viral risk during xenotransplantation. In this context, special attention should be directed towards productive infection of human endothelial cells: in the setting of xenotransplantation this cell type will have close contact with porcine cells and PERV particles.

Animals↗
PubMed2000

Infection of nonhuman primate cells by pig endogenous retrovirus.

The ongoing shortage of human donor organs for transplantation has catalyzed new interest in the application of pig organs (xenotransplantation). One of the biggest concerns about the transplantation of porcine grafts into humans is the transmission of pig endogenous retroviruses (PERV) to the recipients or even to other members of the community. Although nonhuman primate models are excellently suited to mimic clinical xenotransplantation settings, their value for risk assessment of PERV transmission at xenotransplantation is questionable since all of the primate cell lines tested so far have been found to be nonpermissive for PERV infection. Here we demonstrate that human, gorilla, and Papio hamadryas primary skin fibroblasts and also baboon B-cell lines are permissive for PERV infection. This suggests that a reevaluation of the suitability of the baboon model for risk assessment in xenotransplantation is critical at this point.

Animals↗
PubMed1999

[Prehospital thrombolysis with rt-PS. Reperfusion strategy in a time management concept of acute myocardial infarct].

PATIENTS AND METHOD: Prehospital thrombolysis was performed on 93 patients during a time period of 6 years (3/1992 to 9/1998) in an urban area. Thrombolysis with rt-PA (20 mg rt-PA bolus, 30 minute infusion with 30 mg rt-PA) could be started within 2 hours after the onset of symptoms in 67 patients (73.6%). RESULTS: The time gain from prehospital thrombolysis amounted to 38 +/- 14 minutes. Bleeding complications were not observed in the prehospital setting, but 2 patients suffered from intracerebral hemorrhage subsequently and died in the hospital. An aborted infarction (CKmax < 200 U/l and no new Q-waves) was observed in 18 patients (20%) and another 23 patients (25%) had a limitation of infarct size (CKmax < 500 U/l or no new Q-waves) despite obvious signs of myocardial ischemia in the first ECG. CONCLUSION: Our experience demonstrates a considerable time gain for prehospital thrombolysis even for an urban area. Accelerated rt-PA is a safe and comfortable thrombolysis regime.

Adult↗
PubMed1999

Is normal pregnancy atherogenic?

Serum cholesterol, triacylglycerols and low-density lipoprotein (LDL) subfractions were determined in 120 primagravid women during normal gestation (40 in each trimester) and in 20 non-pregnant age-matched controls. LDL subfractions were determined by PAGE, and an LDL score was calculated. The higher the score, the smaller the subfractions. The objective of the study was to determine the effects of the hyperlipidaemia, high oestrogen concentrations and insulin resistance known to exist in normal pregnancy on LDL subfraction formation. Pregnant women had an increased mean serum cholesterol concentration [5.78 (S.D. 1.09) mmol/l] in the first trimester compared with the non-pregnant controls [5.11 (0.77) mmol/l; P<0.01]. The serum cholesterol concentration increased progressively throughout gestation to a mean of 8.14 (1.39) mmol/l in the third trimester (P<0.001 compared with the second trimester). Triacylglycerol concentrations in the first trimester were similar to those of controls, and there was a non-significant increase by the second trimester to 1.32 (0.44) mmol/l. However, by the third trimester the mean triacylglycerol concentration had doubled [2.58 (0.98) mmol/l; P<0.001 compared with the first and second trimester]. During gestation the LDL score increased dramatically, from 1.17 (0.39) during the first trimester to 2.01 (0.37) in the second trimester (P<0.001) to 2.73 (0.48) in the third trimester (P<0.001 compared with the second trimester). Thus an atherogenic lipid profile develops during normal gestation. The significance of these changes remains unclear, but thay may have important implications for mother and foetus.

Adult↗
PubMed1999

Age-independent oxidative stress in elderly patients with non-insulin-dependent diabetes mellitus.

Impaired antioxidant defence is implicated in the development of cardiovascular complications in non-insulin-dependent diabetes (NIDDM). However, as many of these patients are elderly, observed changes in antioxidant status may be due to the patient's age rather than their disease. We sampled blood from 47 elderly NIDDM patients (21 male and 26 female; mean age +/- SD, 75.62 +/- 7.97 years), 66 young (30 male and 36 female; 24.52 +/- 4.72 years) and 58 healthy elderly volunteers (17 male and 41 female; 70.74 +/- 4.85 years), and measured the antioxidant glutathione, the marker for free-radical-damage lipid hydroperoxide products (LHP), vitamin E and total antioxidant capacity (TAC). There was a significant increase in LHP in the healthy elderly group compared with the young volunteers (3.14 +/- 1.5 vs. 2.14 +/- 1.38 mumol/l, p < 0.01). The values were much higher in NIDDM patients (7.02 +/- 2.29 mumol/l, p < 0.0001 vs. healthy elderly). There was a reduction in TAC in healthy elderly compared with the young (359.99 +/- 54.82 vs. 471.47 +/- 94.29 mumol/l trolox equivalents, p < 0.0001), but there was no further reduction in NIDDM patients. Similarly, glutathione was reduced to the same degree in healthy elderly and NIDDM patients (0.29 +/- 0.09, 0.30 +/- 0.11 vs. 0.54 +/- 0.19 mumol/l in young volunteers, p < 0.0001). Vitamin E concentrations were comparable in all groups (26.34 +/- 5.39 young volunteers, 31.50 +/- 8.23 healthy elderly and 30.98 +/- 9.03 mumol/l NIDDM patients), but after correction for serum cholesterol there was a significant reduction in the diabetic group compared with the young, but not with the elderly (5.54 +/- 1.55 vs. 6.67 +/- 1.86 vs. 6.31 +/- 1.85 (mumol/l)/(mmol/l), p < 0.01). We have demonstrated an age-dependent reduction in total antioxidant capacity and glutathione defence and an age-independent increase in LHP in elderly patients with NIDDM. Reduced concentrations of vitamin E were demonstrated in NIDDM patients compared with young, but not elderly, volunteers. Increased oxidative damage occurs independently of age in NIDDM patients despite comparable antioxidant defences in this age group.

Adult↗
PubMed1999

Anti-L-selectin antibody treatment of hemorrhagic-traumatic shock in baboons.

OBJECTIVES: The adhesion molecule L-selectin plays an important role in leukocyte-endothelium interactions, thereby contributing to inflammatory reactions. We tested the hypothesis that humanized anti-L-selectin antibodies reduce trauma-associated organ damage and mortality. DESIGN: Prospective, randomized experimental study. SETTING: Independent nonprofit research laboratory in a trauma hospital (Ludwig Boltzmann Institute) and a contract research institute (Biocon). SUBJECTS: Twenty-eight male baboons (Papio ursinus), 18 to 29 kg. INTERVENTIONS: Hemorrhagic-traumatic shock was created by complement activation with cobra venom factor, followed by withdrawal of blood to a mean arterial pressure of 35 to 45 mm Hg. Blood and lactated Ringer's solution were reinfused. Animals were randomized to receive either 2 mg/kg humanized anti-L-selectin antibody (HuDREG-55 [Ab]) or placebo (lactated Ringer's solution [LRS]). MEASUREMENTS AND MAIN RESULTS: Treatment with humanized anti-L-selectin antibody decreased mortality (Ab 21% vs. LRS 71%; p = .011) and improved survival time (p = .016). A trend toward reduced organ damage, especially in the adrenal glands (score 1.2 +/- 0.2 placebo vs. 1.0 +/- 0.1 antibody; p = .059) was seen, and at 24 hrs was accompanied by significantly increased mean arterial pressure (Ab 99 +/- 6 mm Hg vs. LRS 79 +/- 8 mm Hg; p = .023), cardiac output (Ab 3.4 +/- 0.2 L/min vs. LRS 2.4 +/- 0.3 L/min; p = .007), core temperature (p = .048), and improved perfusion, with less negative base excess (Ab 2.9 +/- 1.1 vs. LRS 2.1 +/- 1.7; p = .019) and a trend toward less lactate (p = .065). These improvements were accompanied by significantly (p = .006) decreased fluid requirements in the treatment group (Ab 11.7 +/- 2.5 mL/kg/hr vs. LRS 23.0 +/- 2.3 mL/kg/hr). There were also fewer circulating leukocytes (p = .042) in the treatment group at 24 hrs. CONCLUSION: Humanized anti-L-selectin antibody has beneficial effects on survival in a long-term in vivo model of hemorrhagic. traumatic shock.

Animals↗
PubMed1999

Current clinical use of reteplase for thrombolysis. A pharmacokinetic-pharmacodynamic perspective.

Clinical evaluation of a new thrombolytic agent should start with a dose that provides adequate efficacy and has an acceptably low bleeding risk; this results in a narrow therapeutic window at the upper end of the dose-response curve. Angiographic patency of the infarct-related artery is still the clinical surrogate end-point for mortality in phase II dose-ranging studies. There is experimental and clinical evidence that the area under the concentration-time curve (AUC) for plasminogenolytic activity of a thrombolytic agent is positively correlated with patency of the infarct-related artery. Dose-ranging studies of the novel recombinant plasminogen activator reteplase in healthy volunteers enabled computation of a linear regression curve by which a clinical starting dose could be calculated for an adapted target AUC that would be clinically effective. Pharmacokinetic analysis also revealed that the half-life of reteplase is 4 times longer than that of the reference thrombolytic alteplase, thus allowing bolus injection. The suggested single bolus starting dose of 10U was supported by results from studies in a canine model of coronary thrombolysis. The feedback of insufficiently high patency rates compared with the increased efficacy of front-loaded and accelerated alteplase demanded optimisation strategies for reteplase. Animal experiments suggested that a double bolus regimen of reteplase would be preferable to doubling the single bolus dose. Pharmacokinetic modelling suggested a time interval of 30 min between the 2 bolus injections. Selection of the tested double bolus regimens was conservative and empirical. First, the previously tested single bolus of 15U was divided to 10 + 5U; secondly, the second bolus dose was increased to 10U. This strategy proved to be successful. The current dosage recommendation for reteplase is a double bolus intravenous injection of 10 + 10U, each over 2 min, 30 min apart. This produces a reduction in mortality in patients with acute myocardial infarction that is equivalent to that produced by front-loaded and accelerated infusion of alteplase.

Animals↗
PubMed1999

[Porcine endogenous retroviruses (PERV): in vitro artifact or a big problem for xenotransplantation?].

The pig is the favorized donor species for clinical xenotransplantation. However, PATIENCE et al. could show, that porcine endogenous retroviruses (PERV), released by a porcine kidney cell line, are capable of infecting human cell lines in vitro. Based on this discovery there is an ongoing discussion concerning the risks of zoonosis combined with xenotranplantation, which culminated in the demand for a moratorium on clinical transplantation of porcine organs. Recent findings exclude the possibility of an artifact due to the use of an immortalized cell line: Release of infectious PERV was also shown for mitogenic stimulated primary porcine peripheral blood mononuclear cells and, even more important, for primary porcine endothelial cells. In contrast, none of the recent retrospective in vivo studies showed evidence for PERV transmission, neither in patients after transplantation of porcine pancreas islet cells or after extracorporal perfusion of porcine kidneys, nor in baboons after transplantation of porcine endothelial cells. Currently it is not known, whether impairments of the immunological responses against foreign pathogens, which are associated with different xenotransplantation strategies, could enable PERV in vivo infection. Only in vivo experiments, if possible in suitable subhuman primate models, offer the prospect for a final risk assessment.

Animals↗
PubMed1999

[The "Duisgurg model" of intensified control of nursing homes and homes for the aged by the Duisberg public health services in cooperation with the Duisburg social welfare offices].

This is a report on the joint cooperative control of nursing and old-age homes by the Public Health and Social Welfare Offices in Duisburg, Germany. A total of 40 of such homes were inspected and checked jointly by the physician and pharmacist of the local Public Health Office within a one-year period while collecting data on the intensity and quality of care in these homes. A total of 3883 inmates were covered. These data included, inter alia, information on the intensity of care, prevalence of urinary and fecal incontinence, feeding by means of percutaneous endoscopic gastrostomy, prevalence of bedridden patients and of cases of pressure sores. The data conveyed information on the overall situation (frequencies for all the Duisburg nursing and old-age homes) on the one hand, and for each individual home on the basis of its particular data on the other hand. It became evident that two-thirds of all the inmates of nursing homes were classified as belonging to nursing stages II and III. Urinary incontinence was present in 63 per cent of the cases, fecal incontinence in 43 per cent, whereas 32 per cent were severely confused. Of a total of 447 permanently bedridden patients (11.5 per cent of all the inmates) 131 had pressure sores or necroses of the heels (3.37 per cent of the total population). More than one-half of the pressure sores had been acquired by the patients during their hospital stay, i.e. before their referral to a home, whereas 56 inmates developed their pressure sores in the homes concerned.

Aged↗
PubMed1998

Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells.

BACKGROUND: The risk of interspecies transmission of retroviruses during xenotransplantation is suggested by reports of pig endogenous retrovirus (PERV) released from porcine cell lines productively infecting human cell lines in vitro and of infectious PERV being released from pig peripheral blood mononuclear cells after mitogenic stimulation. Endothelial cells are the main interface between a xenograft and the recipient's leucocytes and tissues. METHODS: We have analysed pig primary aortic endothelial cells (PAEC) together with other transplantation-relevant porcine cells and tissues for expression of PERV mRNA. Release of virus particles by PAEC was monitored by reverse transcriptase (RT) activity in the medium of cultured PAEC. Infectivity for human cells was tested by co-cultivation of irradiated PAEC with the human embryonal kidney cell line HEK293 and looking for virus release from the human cells. FINDINGS: PAECs, hepatocytes, lung, and skin from a variety of pig strains and breeds expressed PERV mRNA. PAEC released infectious particles. Co-cultivation of PAEC and HEK293 led to productive infection of the human cells and expression of PERV types A and B. INTERPRETATION: Release of infectious virus from PAEC occurred without mitogenic stimulation, suggesting a serious risk of retrovirus transfer after xenotransplantation.

Animals↗
PubMed1998

Porcine endogenous retrovirus (PERV) was not transmitted from transplanted porcine endothelial cells to baboons in vivo.

The discussion about the clinical risk of zoonoses in xenotransplantation has recently culminated in the demand for a moratorium on clinical organ transplantation using pig donors. The basis for this discussion was a recent report showing a possible trans-species transmission of pig endogenous retrovirus (PERV) by in vitro transfer to human cell lines. At present, it remains unclear if this could also happen in vivo or in the setting of xenotransplantation. Potential in vivo transfer of PERV after xenotransplantation was investigated in an experimental pig-to-baboon cell transplantation model. Baboons were immunosuppressed with high-dose cyclophosphamide (total 45-150 mg/kg) and transplanted with primary porcine aortic endothelial cells (PAEC). Tissue samples (skin, lymph nodes, lung) and peripheral blood leukocytes of 15 baboons, taken about 12-24 months after transplantation of PAEC, were then analyzed by PCR and showed no PERV infection. PERV expression in PAEC was also analyzed: PERV mRNA and reverse transcriptase in the culture supernatant could be detected. In spite of the release of retroviral particles from cultured PAEC, transplantation of these cells into baboon recipients did not result in virus transmission, not even under heavy immunosuppression.

Animals↗
PubMed1998

Non-pharmacological modification of cardiac risk factors: part 3. Smoking cessation and alcohol consumption.

Smoking cessation (SC) is probably the single most important risk factor modification for both primary and secondary prevention of cardiovascular disease. Interventions to stop smoking are highly cost effective. SC produces reductions in mortality and morbidity that generally outweigh any increase in risk due to weight gain, unless the gain is so great that it is accompanied by adverse changes in blood pressure, lipid profile or glucose tolerance. There is clear evidence that SC improves the lipid profile, decreases thrombotic tendency, reduces vascular endothelial damage and improves insulin sensitivity. Epidemiological studies consistently demonstrate a reduced risk of developing coronary heart disease (CHD) with moderate alcohol consumption (showing protection at < or = 2 drinks per day), but an increased risk at higher alcohol consumption levels. Potential mediators of these cardioprotective effects include an increase in high-density cholesterol (HDL-C), decreased clotting propensity, enhanced insulin sensitivity and glucose tolerance, and a possible lowering of blood pressure at low consumption levels in women. Alcohol consumption may not, however, compensate for the large increase in risk produced by smoking. Whereas moderate alcohol consumption slightly reduces the risk of death between the ages of 35 and 69 years, cigarette smoking approximately doubles the risk.

Adult↗