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Biomedical subjects

B Risberg

Publications and source records attributed to B Risberg.

At least 109 records · Page 6Linked to original sources
PubMed1996

Localization of fibrinolytic activators and inhibitors in normal and atherosclerotic vessels.

UNLABELLED: Local fibrinolytic changes in atherosclerotic arteries have been suggested to influence plaque growth and promote mural thrombosis on ruptured or ulcerated plaques. Increased levels of plasminogen activator inhibitor (PAI-1) have been found in atherosclerotic arteries. In this study tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and PAI-1 were localized in arterial biopsies of healthy and atherosclerotic vessels by immunohistochemistry. The expression of fibrinolytic regulators was related to the distribution of endothelial cells (EC) and macrophages. RESULTS: t-PA was expressed in vasa vasorum. PAI-1 was positive in endothelial cells, in the media and in the adventitia. Increased expression of t-PA, u-PA and PAI-1 was found in atherosclerotic vessels. t-PA, u-PA, PAI-1 and macrophages were co-localized in plaques. These results support the concept that macrophages can be important in the local regulation of fibrinolysis in atherosclerotic vessels.

Adult↗
PubMed1995

Interferon-gamma modulates the fibrinolytic response in cultured human endothelial cells.

The fibrinolytic potential of the endothelial cells gives important antithrombotic properties to the vascular wall. Thrombosis is a frequent complication to atherosclerosis and other conditions where inflammatory mediators are present in the vascular wall. Inflammatory agents like lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF alpha) have been demonstrated to modulate the expression of fibrinolytic factors in cultured endothelial cells. In the present study the expression of tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) antigen in conditioned medium from cultured human umbilical vein (HUVEC) and human saphenous vein (HSVEC) endothelial cells was investigated under basal conditions and after stimulation with LPS, TNF alpha, interferon-gamma (IFN-gamma) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNF alpha increased the expression of PAI-1, u-PA and PAI-2 in HUVEC and HSVEC, while the t-PA response differed between the two cell types. The effects of TNF alpha were modulated by IFN-gamma but not by IL-6. The increased expression of u-PA after stimulation with TNF alpha was reduced by IFN-gamma. In contrast, TNF alpha-induced expression of PAI-2 was synergistically increased by addition of IFN-gamma. These effects of IFN-gamma represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction.

Adult↗
PubMed1995

The vaginal epithelium in the postmenopause--cytology, histology and pH as methods of assessment.

In the study of postmenopausal vaginal oestrogen deficiency, an objective assessment of the vaginal epithelium is necessary. The present study was undertaken to evaluate different methods for assessing the vaginal epithelium, during atrophic and mature conditions. The vaginal epithelium was assessed by clinical examination, pH and vaginal cytology, including morphometric analysis, before and after oestrogen treatment. Biopsies of the vaginal wall were studied using descriptive histology and immunohistochemistry methods. The antigen Ki-67, a sensitive marker of cell proliferation, was detected using the monoclonal antibody MIB1. When comparing pre- and post-treatment values from the methods, a shift towards mature values was observed, but the magnitude of the shift differed to a considerable extent. Vaginal cytology, expressed as mean maturation index (MI) shifted significantly from 94/6/0 to 0/65/35. Likewise, mean pH was significantly shifted from 6.2 to mean 4.5. The increased presence of Ki-67 positive cells could be demonstrated after oestrogen treatment, but the range of data was wide, which was also found for the thickness of the epithelium and the number of cell layers. For objective assessment of the vaginal epithelium maturation index and pH can be recommended.

Atrophy↗
PubMed1995

Transdermal hormonal replacement therapy with transdermal progestin every second month.

OBJECTIVES: Unopposed estrogen therapy may induce endometrial hyperplasia. To protect the endometrium, estrogen replacement therapy should be combined with a progestin in menopausal women with an intact uterus. The aim of this open non-comparative study was to evaluate the effects on bleeding control and endometrium of 'spacing-out' the 14-day progestin therapy to every second month during transdermal combined hormonal replacement therapy. METHODS: Sixty-eight healthy women, previously treated with sequential combined transdermal hormonal replacement therapy every month for 3 years, were treated for the following 2 years in cycles with 6 weeks of transdermal estradiol 50 micrograms/daily (Estraderm, Ciba-Geigy), followed by 2 weeks of combined norethisterone acetate 0.25 mg/day and 50 micrograms estradiol per day. RESULTS: Annual endometrial biopsies diagnosed hyperplasia in one woman during the second year whereas most biopsies showed a secretory endometrium. Vaginal ultrasound showed no correlation to either bleeding-pattern or histopathological diagnosis. Most women had a regular bleeding-pattern. CONCLUSIONS: Transdermal progestin every second month might be an alternative to regular monthly sequential hormonal replacement therapy.

Administration, Cutaneous↗
PubMed1995

Transfemoral insertion of a bifurcated endovascular graft for aortic aneurysm repair: the first 22 patients.

The purpose of this study was to evaluate and optimize a system of transfemoral bifurcated graft insertion for endovascular repair of infrarenal aortic aneurysm. Grafts were inserted through bilateral femoral arteriotomies in 22 patients. Placement was guided by fluoroscopy. Results were assessed by completion angiography, with computed tomography scanning or duplex ultrasonography at 1, 3 and 6 months. The first 11 insertions were complicated by failed insertion in two cases, proximal leakage in one, graft limb thrombosis in five and wound infection in one. The second 11 insertions were complicated by retrograde leakage around the distal graft orifice in two patients. One of these was associated with aneurysm rupture, leading to the sole mortality of the series. There were no instances of graft migration or embolism. In conclusion, the lessons learned during the first 11 insertions were responsible for the improved results apparent in the second 11 insertions. When applied in properly selected patients, transfemoral insertion of a bifurcated graft is a reliable method of isolating an aortic aneurysm from the circulation.

Aortic Aneurysm, Abdominal↗
PubMed1995

Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower limb ischaemia: a prospective randomised controlled study.

OBJECTIVES: This study was designed to test the hypothesis that spinal cord stimulation (SCS) improves limb salvage in patients with inoperable severe leg ischaemia. DESIGN: Prospective randomised controlled study with 18 months follow-up. SETTING: Vascular surgical units in two university hospitals. MATERIALS: Atherosclerotic (n = 41) and diabetic (n = 10) patients having chronic leg ischaemia with rest pain and/or ischaemic ulcerations due to technically inoperable arterial occlusions. CHIEF OUTCOME MEASURES: Limb salvage and amount of tissue loss within 18 months, pain relief. MAIN RESULTS: Twenty-five patients were randomized to SCS and 26 to analgesic (control) treatment. Macrocirculatory parameters were not different in the two groups during follow-up. Long-term pain relief was observed only in the SCS group. At 18 months, limb salvage rates in the SCS and control groups were 62% and 45% (N.S.). Tissue loss was less (p = 0.05) in the SCS group. A subgroup analysis of patients without arterial hypertension showed a significantly lower amputation rate in the SCS vs the control group. CONCLUSIONS: SCS provided long-term pain relief but limb salvage at 18 months was not significantly improved by SCS in this rather small study. The results suggest that SCS may reduce amputation levels in patients with severe inoperable leg ischaemia and be most effective in patients without arterial hypertension.

Aged↗
PubMed1995

Colour Doppler ultrasound in diagnosing venous insufficiency. A comparison to descending phlebography.

OBJECTIVE: To evaluate the technique of ultrasound colour Doppler in diagnosing venous valvular incompetence in the lower leg. DESIGN: Prospective clinical study. SETTING: Department of clinical physiology. MATERIALS: 44 patients (56 legs) referred with a clinical diagnosis of deep venous insufficiency. CHIEF OUTCOME MEASURES: Colour Doppler and descending phlebography. MAIN RESULTS: Using phlebography as a "gold standard" the accuracy of the colour Doppler technique varied between 93% and 55% for the different veins. For the superficial and deep femoral veins, the popliteal vein and the long and short saphenous veins the accuracy was between 90% and 70%. The lowest correlation was found for the deep calf veins (55-66% accuracy). CONCLUSIONS: Colour Doppler was found to be a suitable technique for non-invasive investigation of patients with suspected venous insufficiency. Since the colour Doppler technique is non-invasive it is well suited for follow-up studies. Descending phlebography should be reserved as an adjunct technique in patients scheduled for valve reconstructive surgery.

Adolescent↗
PubMed1995

Oral ciprofloxacin versus intravenous cefuroxime as prophylaxis against postoperative infection in vascular surgery: a randomised double-blind, prospective multicentre study.

OBJECTIVES: To test the hypothesis that oral ciprofloxacin is equally effective as intravenous cefuroxime in preventing postoperative infectious complications in patients undergoing peripheral arterial surgery involving the groins. DESIGN: Prospective, randomised, double-blind multicentre study. MATERIALS: 580 patients undergoing arterial surgery involving the groins were randomised to ciprofloxacin (Ciproxin, Bayer) 750 mg x 2 p.o. or cefuroxime (Zinacef, Glaxo) 1.5 g x 3 i.v. given only on the day of surgery. The primary endpoint was wound/graft infection within 30 days postoperatively. Wound infection was defined as pus. RESULTS: The wound infection rate in the ciprofloxacin group was 9.2% (27 patients) and in the cefuroxime group 9.1% (26 patients) according to intention to treat. For correct treatment the corresponding numbers were 9.5% (23 patients) and 9.7% (22 patients), respectively. There were three graft infections (0.5%). The infection rate was 7.1% (31/433) in the absence and 14.9% (22/147) in the presence of distal ulcers (p < 0.05). S. allreus was the most common bacteria isolated. Forty percent of the wound infections were localised to the groins. By multivariate analysis presence of distal ulcer was the only factor of prognostic significance. CONCLUSIONS: The infection rate was similar in the two groups. Thus, oral administration of ciprofloxacin is an attractive, cost-effective and safe alternative to prophylaxis in vascular patients capable of taking oral medication on the day of surgery.

Administration, Oral↗
PubMed1995

NBT reactivity correlates to the distribution of PMNs between rat pulmonary and systemic circulation.

The rat systemic and pulmonary vascular transit times of radiolabeled polymorphonuclear granulocytes (experimental population referred to as "Polys") and mononuclear leukocytes (experimental population referred to as "Monos") (111In) in relation to those of erythrocytes (51Cr) were measured under physiological conditions. Results were also expressed as "circulating" pool and "marginated" pool of the two leukocyte fractions, and it was investigated whether the degree of spontaneous granulocyte activation, measured with the nitro blue tetrazolium (NBT) reduction test, was of importance for the retention of Polys in the lungs. The measured mean vascular transit was similar for Monos and Polys and several times slower than that of the erythrocytes in the pulmonary (17.4 times) and the systemic (4.1 times) vascular beds. The percentage of NBT-positive cells was < 10% in most animals, indicating a low level of spontaneous granulocyte activation. Increasing levels of NBT-positive cells correlated with a redistribution of granulocytes from the systemic marginated cell pool to the pulmonary marginated cell pool. Microscopic evaluation of sections from embedded lung tissue biopsies, obtained after intravital staining of the leukocytes, confirmed the isotope data on pulmonary transit.

Animals↗
PubMed1995

Ascorbate preserves gastric mucosal metabolism and microcirculation after hemorrhagic shock and retransfusion in rats.

The gastric mucosal microcirculation and purine nucleotide metabolism were studied in rats after hemorrhagic shock and retransfusion. The mucosal surface density of perfused vessels (SDPV) and the mucosal levels of ATP, ADP, AMP, IMP, hypoxanthine and uric acid were measured following 15 min of hemorrhagic shock and 10 and 30 min after retransfusion, and the effects of pretreatment with allopurinol or ascorbate were studied. During shock there was a dephosphorylation of nucleotides and a decline in the SDPV. Retransfusion led to an additional reduction in the SDPV, but a complete restoration of preshock nucleotide levels 30 min after retransfusion. Allopurinol accelerated early rephosphorylation of nucleotides without effects upon SDPV while ascorbate completely preserved the mucosal level of energy-rich nucleotides 15 min after hemorrhagic shock and increased SDPV during early reperfusion. The results showed that there was a renewal of energy stores in gastric mucosa after hemorrhagic shock and retransfusion although parts of the vascular bed were not reperfused. The mucosal energy depletion after 15 min of hemorrhagic shock and part of the mucosal vessel injury after retransfusion were prevented by pretreatment with ascorbate.

Allopurinol↗
PubMed1995

Ki-67 immunostaining of endometrial biopsies with special reference to hormone replacement therapy.

BACKGROUND: The purpose of this investigation was to evaluate the Ki-67 immunostaining method on formalin-fixed, paraffin-embedded endometrium and to use the method on endometrial biopsies from 30 postmenopausal women treated with 2 mg estradiol and different doses of natural micronized progesterone (50, 100 or 200 mg). METHODS: Two technicians prepared the immunostaining of slides from each of 12 endometrial specimens and 3 different observers estimated the Ki-67 immunostaining. One observer estimated all the slides 3 times on different occasions. The percentage of immunopositive nuclei in glandular epithelium was evaluated. RESULTS: The dominating component of variation for this method was between observers, with a median standard deviation of 20%. A total median variation including all components rendered a standard deviation of 23%. No significant effects of different technicians, preparations, or from the same observer on different occasions were found. In the major part of the biopsies from women on hormone replacement therapy (HRT), only 0-10% of the glandular epithelium was Ki-67 stained. CONCLUSION: Ki-67 immunostaining is an adequate technique to use when evaluating the effects of HRT on the endometrium. The main source of variation is between observers and not the technique of preparing the slides.

Biopsy↗
PubMed1995

p53 and Rb immunostaining in locally advanced bladder cancer: relation to prognostic variables and predictive value for the local response to radical radiotherapy.

The association between known prognostic variables and altered immunostaining for the nuclear proteins retinoblastoma (Rb) and p53 was studied in a homogeneous series of locally advanced bladder cancer. The predictive value of this immunostaining for the local response to intended radical radiotherapy was investigated. Among 262 patients treated with intended radical radiotherapy between 1967 and 1986, a total of 154 patients were evaluable with respect to local response to treatment. The paraffin-embedded specimen from the tumour prior to irradiation was immunostained with the monoclonal antibodies PMG3-245 for Rb and 1801 for p53 nuclear proteins after heating in a microwave oven for 40 min at 650 W. An altered expression of Rb and p53 was observed in 18 and 42% of the tumours, respectively. p53 overexpression was associated with higher tumour grade. However, the results of the p53 and Rb immunostaining procedures had no predictive value for tumor response to radiation treatment, local control or cancer-specific mortality.

Adult↗
PubMed1995

Complex intracellular signal transduction regulates tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) synthesis in cultured human umbilical vein endothelium.

Endothelial cells are central in fibrinolysis because of their high production of both activators (t-PA, uPA) and inhibitors (PAI-1). The t-PA and PAI-1 synthesis could be regulated by signals transduction at several cellular levels. The purpose of this in vitro study, on cultured endothelial cells, was to explore the receptor/second messenger regulation of the t-PA and PAI-1 synthesis. Quiescent confluent human umbilical vein endothelial cells, cultured in passage 1, were exposed to different test substances. Samples from the conditioned medium were collected after 16 and 24 h and analysed for t-PA and PAI-1 antigen. All data presented were related to the data from control dishes (= 100%), in the same experiment. The results from the present study (mean +/- 95% confidence interval) demonstrated the following. (1) Forskolin, with a documented direct cAMP-inducing effect, decreased the basal PAI-1 production to 61 +/- 15%, and Na-nitroprusside, with a documented cGMP-inducing effect, increased the basal PAI-1 production to 141 +/- 38% without affecting the basal t-PA production. The surface receptor agonists isoprenalin or ephedrine, which indirectly affect adenylate cyclase, had no effect on t-PA or PAI-1 production. (2) Phorbolester (PMA), which directly activates proteinkinase C (PKC), increased the basal t-PA and PAI-1 production to 350 +/- 71%, and 163 +/- 35% respectively. (3) Thrombin, but not endothelin-1 (ET-1), increased the basal t-PA and PAI-1 production to 195 +/- 34% and 136 +/- 18%, respectively, indicating an PKC-mediated thrombin effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1995

A comparative study of three low-molecular weight heparins (LMWH) and unfractionated heparin (UH) in healthy volunteers.

The levels of anti-IIa and anti-Xa activity, as reported in laboratory and clinical studies on low molecular weight heparin (LMWH) preparations, show a high degree of variability. This variation has been proposed as correlated to the variation in incidence of postoperative deep vein thrombosis (DVT) (8-30%) in different LMWH studies on comparable populations undergoing elective hip surgery. The aim of this study was to compare the ex vivo potency of Clexane (enoxaparin), Fragmin (dalteparin) and Logiparin (tinzaparin), applying the concept of bioequivalence, although unknown which activity/activities are best correlated to efficacy. Unfractionated heparin (UH) was included in the study as a reference drug. The drugs were studied with a cross-over technique in 12 healthy subjects and given subcutaneously in the doses recommended for orthopedic surgery. Blood samples were drawn each hour up to 10 h and at 12 h after administration. Anti-Xa and anti-IIa activities were measured using chromogenic substrate methods. The anti-Xa peak activity (Cmax) and the area under the curve (AUC) were highest for Clexane and Fragmin and lower for Logiparin and UH. Clexane and Fragmin were considered bioequivalent in anti-Xa activity. Regarding anti-IIa activity, no bioequivalence was found between the products. Fragmin was clearly different, with Cmax and AUC approximately twice as high as the other drugs. Whether the demonstrated differences in anti-Xa and anti-II activities are of any clinical significance remains unclear and can only be established by comparative clinical studies.

Adult↗
PubMed1995

Leukocyte margination during hemorrhagic shock correlates to preshock margination and is reduced by fucoidin.

Systemic and pulmonary circulation kinetics for 51Cr-erythrocytes and 111In-leukocytes were measured in rats during experimental hemorrhagic shock and normotension with or without pretreatment with the antirolling agent fucoidin. Leukocyte margination was expressed as transit factors (white blood cell transit time/red blood cell transit time) for polymorphonuclear and mononuclear cells. There was an increased pooling of leukocytes in the pulmonary and systemic vascular beds during shock with a maximum after 60 min when the transit factors had increased 2.90-3.72 times in the pulmonary vascular bed and 2.00-3.52 times in the systemic vascular bed for mononuclear and polymorphonuclear cells, respectively. High preshock pooling levels lead to a more pronounced increase in pooling during shock. Pretreatment with fucoidin significantly reduced the pooling increase in the systemic vascular bed. Granulocyte oxidative activity (nitro blue tetrazolium test) invariably increased during shock and was not affected by fucoidin.

Animals↗