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Biomedical subjects

M Falkenberg

Publications and source records attributed to M Falkenberg.

At least 19 recordsLinked to original sources
PubMed2006

Remodeling of the thoracic aorta after stent grafting of type B dissection: a Swedish multicenter study.

AIM: Endovascular repair of complicated type B dissections has evolved as a promising alternative to open repair. Previous studies have indicated that continued false lumen flow is a predictor of continued aortic dilatation and risk of rupture during follow-up. This multicenter study was conducted to analyze the postoperative changes of the false lumen after endografting of complicated type B dissections. METHODS: All patients treated with endovascular stent grafts for thoracic type B dissections at 5 major Vascular Centers in Sweden were identified through local databases. Review of charts and all available pre- and postoperative CT scans were performed to identify demographics, indications for repair as well as postoperative changes of the aorta and false lumen. RESULTS: A total of 129 patients treated for type B dissections between 1994 and December 2005 were identified. Median radiological follow-up was 14 months. Fourteen patients died perioperatively leaving 115 patients available for analysis. Seventy-four of these had CT imaging of sufficient quality for morphological analysis. The vast majority of acute patients were treated for rupture or end-organ ischemia whereas most chronic patients were treated for asymptomatic aneurysms. In 80% of patients, the false lumen thrombosed along the stent graft but it remained perfused distal to the stent graft fixation in 50% of patients. Only 5% of patients presented with aortic enlargement of the stent grafted area when adequate proximal sealing was achieved. The distal, uncovered aorta displayed expansion in 16% of patients. CONCLUSIONS: The stent grafted thoracic aorta after type B dissection appears to be stabilized by covering the primary entry site with a stent graft in the majority of both acute and chronic dissections. The uncovered portion of the aorta distal to the stent graft, however, remains at risk of continuous dilatation. Stent grafting for complicated type B thoracic dissections seems to be a treatment option with reasonable morbidity and mortality even though the incidence of severe complications is still significant.

Adult↗
PubMed2001

[Check your waist circumference! Overweight, obesity and abdominal obesity risk factors of type 2 diabetes].

The object with the present study was to present prevalence data in a rural area in Sweden regarding overweight, obesity and abdominal obesity presented by waist circumference. The study was population-based in primary health care. The target group was aged 20 years or more. A total of 91% (n = 6,686) participated. 45% of men and 32% of women were overweight (BMI 25-29.9 kg/m2), 12% of men and 17% of women were obese (BMI > or = 30 kg/m2). The programme found among men 25.8% with a waist circumference 94-101.9 cm and 18.0% > or = 102 cm and among women 22.7% with 80.0-87.9 cm and 27.2% > or = 88 cm. The relative risk for type 2 diabetes increased with waist circumference. Making health care personnel and patients aware of overweight, obesity and abdominal obesity and the risk of associated diseases and encourage a healthy life style is urgent in time of an obesity epidemic.

Abdomen↗
PubMed2001

Effects of hyperbaric oxygen on expression of fibrinolytic factors of human endothelium in a simulated ischaemia/reperfusion situation.

BACKGROUND: Treatment with hyperbaric oxygen (HBO2) is controversial when treating disorders other than decompression sickness. Still, HBO2 is a treatment modality that has gained recognition in certain situations of ischaemia reperfusion. However, not much is known about its effect on the endothelial cells. Based on earlier studies, the hypothesis was that HBO2 treatment stimulates the release of fibrinolytic factors. The aim of the study was to investigate the effect of HBO2 treatment on cultured endothelial cells in a simulated ischaemia-reperfusion model. METHODS: To mimic the clinical situation during ischaemia reperfusion, endothelial cells were subjected to anoxia for 8 h, followed by reperfusion with either HBO2 or normobaric air for 1.5 h, and compared with an untreated control that was not exposed to anoxia. Components investigated were the fibrinolytic stimulator tissue plasminogen activator (t-PA), urokinase plasminogen activator (uPA) and the antagonist. plasminogen activator inhibitor type one (PAI-1). RESULTS: Immediately after 8 h of total anoxia and reoxygenation with HBO2 (for 1.5 h), the mean (SEM) concentrations of t-PA, PAI-1 and uPA were significantly increased compared to the other groups. The difference between the normobaric and control groups, measured at 1.5 h, 6 h and 24 h post-anoxia, persisted throughout the experiment. CONCLUSION: In this ischaemia-reperfusion model. HBO2 stimulates the release of fibrinolytic factors. These observations might be relevant in trauma care in preventing thromboses and/or microembolization following ischaemia-reperfusion.

Cells, Cultured↗
PubMed2001

Abnormal levels of urokinase plasminogen activator protein and tissue plasminogen activator activity in human aortic aneurysms.

OBJECTIVE: To measure the concentrations and activities of plasminogen activators and plasminogen activator inhibitors in human abdominal aneurysms. DESIGN: Laboratory study. SETTING: University hospital, Sweden. MATERIAL: Biopsy specimens from 12 abdominal aortic aneurysms and 8 normal aortas (controls). INTRERVENTIONS: Tissues were homogenised and eluted. The supernatants were assayed for antigens of tissue and urokinase plasminogen activator and plasminogen activator inhibitor 1 and 2. The activities of tissue plasminogen activator and plasminogen activator inhibitor-1 were assayed by ELISA. Frozen sections were immunostained for tissue and urokinase plasminogen activators and for plasminogen activator inhibitor-1. MAIN OUTCOME MEASURES: Concentrations and activities of these activators and inhibitors. RESULTS: The concentration of urokinase plasminogen activator antigen was higher in aneurysmal walls than in normal aortas; it was detected immunohistochemically in aneurysmal but not in normal aortas. The concentration (and the detection immunohistochemically) of tissue plasminogen activator was equal in aneurysmal and normal aortas, but its activity was reduced in the aneurysmal wall. Plasminogen activator inhibitor-1 did not differ significantly between the groups. CONCLUSIONS: Urokinase plasminogen activator may be responsible for the digestion of the media of the aorta and the development of an aneurysm. Reduced activity of tissue plasminogen activator may be responsible for thrombosis in the aneurysm.

Adult↗
PubMed2001

Rep-dependent initiation of adeno-associated virus type 2 DNA replication by a herpes simplex virus type 1 replication complex in a reconstituted system.

Productive infection by adeno-associated virus type 2 (AAV) requires coinfection with a helper virus, e.g., adenovirus or herpesviruses. In the case of adenovirus coinfection, the replication machinery of the host cell performs AAV DNA replication. In contrast, it has been proposed that the herpesvirus replication machinery might replicate AAV DNA. To investigate this question, we have attempted to reconstitute AAV DNA replication in vitro using purified herpes simplex virus type 1 (HSV-1) replication proteins. We show that the HSV-1 UL5, UL8, UL29, UL30, UL42, and UL52 gene products along with the AAV Rep68 protein are sufficient to initiate replication on duplex DNA containing the AAV origins of replication, resulting in products several hundred nucleotides in length. Initiation can occur also on templates containing only a Rep binding site and a terminal resolution site. We further demonstrate that initiation of DNA synthesis can take place with a subset of these factors: Rep68 and the UL29, UL30, and UL42 gene products. Since the HSV polymerase and its accessory factor (the products of the UL30 and UL42 genes) are unable to efficiently perform synthesis by strand displacement, it is likely that in addition to creating a hairpin primer, the AAV Rep protein also acts as a helicase for DNA synthesis. The single-strand DNA binding protein (the UL29 gene product) presumably prevents reannealing of complementary strands. These results suggest that AAV can use the HSV replication apparatus to replicate its DNA. In addition, they may provide a first step for the development of a fully reconstituted AAV replication assay.

DNA Helicases↗
PubMed2000

Leading and lagging strand DNA synthesis in vitro by a reconstituted herpes simplex virus type 1 replisome.

The synthesis of double-stranded DNA by a rolling circle mechanism was reconstituted in vitro with a replisome consisting of the DNA polymerase-UL42 complex and the heterotrimeric helicase-primase encoded by herpes simplex virus type 1. Okazaki fragments 3 kilobases in length and leading strands that may exceed 10 kilobases are produced. Lagging strand synthesis is stimulated by ribonucleoside triphosphates. DNA replication appears to be processive because it resists competition with an excess of (dT)(150)/(dA)(20). The single-strand DNA binding protein ICP8 is not required, and high concentrations of ICP8 can, in fact, inhibit lagging strand synthesis. The inhibition can, however, be overcome by the addition of an excess of the UL8 component of the helicase-primase. Rolling circle replication by the herpesvirus and bacteriophage T7 replisomes appears to proceed by a similar mechanism.

DNA↗
PubMed2000

Local oxygen content in the skin is increased in chronic venous incompetence.

In skin lesions of chronic venous incompetence (CVI) transcutaneous oxygen pressure (tcpO(2)) at the ankle is often reduced. However, in some CVI patients the tcpO(2) during suprasystolic occlusion remains significantly higher than in healthy subjects. The aim of the present study was to investigate which kind of CVI patients develop this phenomenon and whether the higher tcpO(2) during occlusion is caused by a smaller oxygen consumption of the skin or by an increased local oxygen content. The oxygen consumption of the skin was measured by the pO(2) decrease (DeltatcpO(2)/Deltat) after stopping the arterial oxygen supply when the hemoglobin was saturated by oxygen inhalation, i.e., at tcpO(2) values above 120-130 mmHg. By multiplying the tcpO(2) with the mean oxygen solubility coefficient of the skin the content of physically dissolved oxygen is obtained. The decrease of tcpO(2) in the 55- to 45-mmHg range indicates the consumption of oxygen physically dissolved and chemically bound to hemoglobin. It gave a parameter for estimating the local hemoglobin content of the skin. These values and the minimal tcpO(2) after a 5-min arterial occlusion were measured in 14 healthy subjects, in 13 patients with varicose veins, but no skin lesions, in 10 patients with CVI lesions like white atrophy and lipodermatosclerosis and in 16 CVI patients with open venous ulcers. During suprasystolic occlusion tcpO(2) at the ankle remained significantly higher in CVI patients with skin lesions than in the healthy control subjects (25.6 +/- 18.9 versus 8.0 +/- 7.0 mmHg). The steepness of the tcpO(2) decrease caused by cutaneous oxygen consumption in healthy subjects was not significantly different from the CVI patients. In contrast, the decrease of tcpO(2) at the ankle between 55 and 45 mmHg was 1.9 +/- 2.0 mmHg/s in the control group and 0.7 +/- 0.5 mmHg/s in the group with open venous ulcers. These results indicate a higher hemoglobin content in the skin of the CVI patients than in healthy subjects. Obviously, the hemoglobin bound oxygen content in the skin of CVI patients is increased. Thus, a lack of oxygen is unlikely to be the primary reason for the development of skin lesions in CVI.

Administration, Inhalation↗
PubMed1999

Antiviral activity of south Brazilian medicinal plant extracts.

Brazilian plants are potential sources of useful edible and medicinal plants. Hydromethanolic extracts prepared from 54 medicinal plants used in folk medicine to treat infections were screened for antiviral properties against five different viruses (HSV-1, HSV-2, poliovirus type 2, adenovirus type 2 and VSV). Fifty-two percent of the plant extracts exhibited antiviral against one or more tested viruses. More specifically, 42.6% showed activity against HSV-1 (herpes simplex virus type 1), 42.6% against HSV-2 (herpes simplex virus type 2), 26% against poliovirus and 24% against VSV (vesicular stomatitis virus). None of the extracts was active against adenovirus. Trixis praestans (Vell.) Cabr. and Cunila spicata Benth. extracts were further characterized for antiviral activity.

Animals↗
PubMed1999

Steps towards the prevention of obesity and associated complications.

The problem of obesity is often not recognised. For example, the prevalence of obesity in Sweden is estimated to be 10%, but a study of a county of 414358 inhabitants and the records from 41 primary healthcare centres found that only 949 (3.1%) of patients were registered as obese. This is alarming, since overweight and obesity can be easily identified and the prevention and treatment of obesity is crucial in order to prevent type 2 diabetes. A screening programme in Kisa, a district of southern Sweden, found that 45% of men and 32% of women were overweight (BMI 25-30 kg/m2), while 12% of men and 17% of women were obese (BMI >30 kg/m2). Among people without diagnosed diabetes, a family history of obesity emerged in 1384 subjects; 707 were overweight or obese (BMI >25 kg/m2), with 270 of these having abdominal obesity. Of 212 of these patients who agreed to an oral glucose tolerance test, 16 were found to have type 2 diabetes and 70 impaired glucose tolerance. It is vital that primary healthcare teams become more active in developing co-ordinated programmes of identification, registration and long-term management of overweight and obese people.

Diabetes Mellitus, Type 2↗
PubMed1999

Treatment with hyperbaric oxygen affects endothelial cell fibrinolysis.

OBJECTIVE: To investigate the effect of hyperbaric oxygen treatment (HBO) on the thrombolytic properties of endothelial cells. SETTING: University hospital, Sweden. INTERVENTIONS: Human endothelial cells were derived from saphenous veins, and exposed to oxygen in a compression chamber at 2.5 atmospheres absolute (ATA, =250kPa). Cells exposed to 2.5 ATA with a gas mixture similar to air (HB Air), and unpressurised air-exposed cells served as controls. MAIN OUTCOME MEASURES: Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). RESULTS: Immediately after treatment there was a significant increase in t-PA protein in the medium in cultures treated with HBO compared with HB Air (p = 0.015, n = 6), and untreated controls (p = 0.015, n = 6). The PAI-1 concentration in media was also higher in the HBO-treated group compared with HB Air (p = 0.004, n = 6) and untreated controls (p = 0.004, n = 6). Six hours after treatment there was still a significant increase in PAI-1 in the HBO-treated group compared with untreated controls (p = 0.007, n = 6), but not with the pressure control. t-PA concentrations were similar. Specific mRNA for t-PA and PAI-1 was detectable immediately after treatment and six hours later in all experimental groups as assessed by reverse transcriptase polymerase chain reaction (RT-PCR). HBO increased the gene expression for both t-PA and PAI-1. CONCLUSIONS: HBO affects endothelial cell function and its fibrinolytic response. These findings may have clinical relevance in hyperbaric medicine and trauma care.

Adult↗
PubMed1998

The herpes simplex virus type 1 helicase-primase. Analysis of helicase activity.

The rate of unwinding of duplex DNA by the herpes simplex virus type 1 (HSV-1)-encoded helicase-primase (primosome) was determined by measuring the rate of appearance of single strands from a circular duplex DNA containing a 40-nucleotide 5' single-stranded tail, i.e. a preformed replication fork, in the presence of the HSV-1 single strand DNA-binding protein, infected cell protein 8 (ICP8). With this substrate, the rate at low ionic strength was highly sensitive to Mg2+ concentration. The Mg2+ dependence was a reflection of both the requirement for ICP8 for helicase activity and the ability of ICP8 to reverse the helicase reaction as a consequence of its capacity to anneal homologous single strands at Mg2+ concentrations in excess of 3 mM. The rate of unwinding of duplex DNA by the HSV-1 primosome was also determined indirectly by measuring the rate of leading strand synthesis with a preformed replication fork as template in the presence of the T7 DNA polymerase. The value of 60-65 base pairs unwound/s by both methods is consistent with the rate of 50 base pairs/s estimated for the rate of fork movement in vivo during replication of pseudorabies virus, another herpesvirus. Interaction with the helicase-primase did not increase its helicase activity.

Base Sequence↗
PubMed1998

Heterogeneous distribution of macrophages, tumour necrosis factor alpha, tissue factor and fibrinolytic regulators in atherosclerotic vessels.

OBJECTIVE: To assess the representativity of small vascular samples with regard to the expression of six important factors in atherosclerotic vessels. MATERIALS: Circumferential frozen sections of iliac and femoral arteries (n = 9) from patients undergoing reconstructive bypass surgery. METHODS: Immunohistochemistry with antibodies against macrophages (CD68), tumour necrosis factor alpha, tissue factor, tissue plasminogen activator, urokinase plasminogen activator and plasminogen activator inhibitor type 1. The distribution of these antigens was characterised by computer assisted image analysis. Antigen positive area in randomly chosen samples of varying size was compared with antigen positive area in the whole vessel transections. RESULTS: Marked heterogeneity was found with respect to the expression of these factors in atherosclerotic vessels. The representativity of samples was highly dependent on the size of the samples. PAI-1 was more evenly expressed compared to the other antigens. CONCLUSIONS: Estimates of the expression of these factors based on small samples from atherosclerotic arteries are unreliable.

Antigens, CD↗