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Biomedical subjects

B Risberg

Publications and source records attributed to B Risberg.

At least 199 records · Page 11Linked to original sources

Lysosomal enzyme pattern in lung lymph and blood during E. coli sepsis in sheep.

Systemic release of lysosomal enzymes and local release in the pulmonary microcirculation from sequestrated and activated leucocytes could be an important factor in the development of the lung microvascular injury seen after septicaemia. The maximal activities of 11 lysosomal acid hydrolases (acid phosphatase, alpha- and beta-glucosidase, alpha- and beta-galactosidase, alpha-mannosidase, beta-acetylglucosaminidase, beta-glucuronidase, arylamidase and cathepsins B and C) were measured in serum and lung lymph from seven sheep before and after infusion of live E. coli bacteria. In the early phase of septicaemia (the first hour) the activities of eight enzymes were increased in serum and/or lung lymph (1.1 to 2X pre-infusion values). In the late phase, 3-4 h after sepsis, there were significantly elevated serum activities of beta-glucosidase (5.4X), alpha- and beta-galactosidases (2.7X, 1.5X), beta-acetylglucosaminidase (2.0X) arylamidase (1.2X) and cathespin B (1.7X). In lymph acid phosphatase (1.7X), alpha- and beta-glucosidases (1.6X, 6.4X), alpha- and beta-galactosidases (2.1X, 1.7X). Beta-acetylglucosaminidase (2.6X), and beta-glucuronidase (4.0X pre-infusion) were elevated. The findings of a heterogenicity of changes in serum and lymph activities, as well as the large molecular sizes of some of the enzymes with changed activities indicated to us that permeability changes were not major causes of increased lymph enzyme activities. The results could indicate a local release of enzymes either from sequestrated leucocytes or lung tissue due to local reactions in the lung or lung microvessels. The heterogenous changes in activities for the various lysosomal enzymes as found in the present study indicated that measurement of only one enzyme could be misleading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sepsis in sheep reduces pulmonary microvascular sieving capacity.

The changes in pulmonary microvascular permeability in sheep, after infusion of live Escherichia coli, were studied using estimations of the osmotic reflection coefficients (sigma) for total protein, albumin, immunoglobins (Ig) G and M and based on these estimations equivalent pore dimensions were calculated. A chronic lung lymph fistula was prepared in seven sheep. After a base-line period, left atrial pressure (Pla) was increased. E. coli (10(9) X kg body wt) were given after attaining filtration independent L/P values. The sigma's for the normal lung were calculated to 0.73 for total protein and to 0.65, 0.76, and 0.91 for albumin, IgG, and IgM, respectively. The equivalent pore radii were determined to 50 and 175 A with 35% of the filtration accounted for by the large pores. After bacterial infusion, the sigma's for total protein, albumin, IgG, and IgM decreased significantly from preseptic values to 0.58, 0.50, 0.64, and 0.83, respectively. After sepsis the small pores were 50 A and the large pores 200 A with 49% of total volume flow at maximum lymph flows occurring through the large pores. Assuming a constant small-pore population the large-pore number increased 32% after bacterial infusion. These results indicate that pulmonary microvascular permeability may have increased due to the sepsis.

Animals↗

Estimation of equivalent pore radii in pulmonary microvasculature after lung lymph fistula preparation.

The effect of lung lymph fistula preparation on pulmonary microvascular permeability was investigated in sheep. Acutely prepared animals (n = 9) were compared with animals with a chronic lung lymph fistula (n = 5). The osmotic reflection coefficients (sigma) for total protein, albumin, immunoglobins (Ig) G and M, and the equivalent pore dimensions were calculated. Data were achieved at maximal possible lymph flows (QL) following elevation of left atrial pressure. In sheep with a chronic lung lymph fistula sigma's for total protein, albumin, IgG, and IgM at maximal lymph flows were 0.76 +/- 0.01, 0.65 +/- 0.09, 0.79 +/- 0.03, and 0.91 +/- 0.01, respectively. In the acutely prepared group the minimum lymph-to-plasma protein concentration for total protein was 0.39 +/- 0.06, corresponding to a sigma of 0.61 +/- 0.01. The sigma for albumin, IgG, and IgM were 0.48 +/- 0.04, 0.64 +/- 0.02, and 0.87 +/- 0.01, respectively. The equivalent pore radii in the chronic group were determined to be 54 and 190 A with 29% of the filtration accounted for by large pores. In the acute group the small pores were 56 A and the large pores 175 A with 53% of total volume flow at maximum lymph flows occurring through the large pores. Assuming a constant small-pore population the large pore number increased 4.5 times after surgery. For total protein, IgG, and IgM, sigma's in the acutely prepared group were significantly lower than in the control group. These results thus indicate that surgical preparation of a lung lymph fistula in sheep may cause acute increases in pulmonary microvascular permeability.

Animals↗

Lipid peroxidation is not a major factor involved in the edema formation in perfused lungs.

Perfusion of isolated rat lungs was previously found to induce edema formation, which was considered to be mediated by oxygen-free radicals as scavengers reduced the edema. In the present study we elaborated upon these findings by measuring products found by O2-radical generation. We measured reduced and oxidized glutathione as well as conjugated dienes as an estimate of lipid peroxidation. Amount of water was also measured. Perfusion with oxygenated dextran/Tyrode solution increased edema as compared to nonoxygenated dextran/Tyrode and to nonperfused control lungs. Induction of oxygen radical formation by addition of xanthine and xanthine oxidase to the nonoxygenated dextran/Tyrode perfusate significantly increased the amount of edema as measured by the percentage of water in the lung to 87.0% as compared to the control value of 78.2%. Addition of the radical scavenger superoxide dismutase and catalase to this perfusate prevented edema accumulation. Levels of conjugated dienes as well as those of reduced and oxidized glutathione in lung tissue were measured before the start of perfusion and after 5 and 30 min of perfusion. No significant changes were seen in any of these parameters, indicating that lipid peroxidation may not be a major factor contributing to the edema formation during perfusion of isolated lungs.

Animals↗

Preoperative irradiation in oral cavity carcinoma. A study with special reference to DNA pattern, histological response and prognosis.

The relation between DNA pattern and response to preoperative radiotherapy was studied in 51 patients with oral squamous cell carcinomas operated 4 weeks after irradiation. Small tumors (T1 and T2) showed more pronounced response to radiotherapy than larger ones (T3 and T4), as did DNA aneuploid tumors. Eight of 11 DNA aneuploid tumors showed no remaining tumor in the operation specimen, compared to 6 of 21 DNA polyploid and 2 of 19 DNA diploid tumors. None of 16 patients without demonstrable remaining cancer in the operation specimen had local recurrence. The presence of lymph node metastases was the most important prognostic factor.

Aneuploidy↗

Prognostic value of consecutive peripheral pressure registration after reconstructive peripheral arterial surgery.

A reliable predictive test as a guide in selection for arterial reconstruction vs. primary amputation would be of great value. An ideal test should also be simple and noninvasive. We evaluated prediction based on preoperative and early postoperative (repeatedly in the first week) measurements of ankle and toe pressure in relation to patency 6 months after reconstructive peripheral vascular surgery in 39 patients. Occlusion occurred within 6 months in ten patients. In eight of them the preoperative ankle-brachial pressure index (ABI) was less than 0.4, but seven other patients with ABI less than 0.4 had maintained patency. In six of the ten with occlusion the toe-brachial pressure index (TBI) was less than 0.1, but in three others with TBI less than 0.1 the grafts were patent. During the first postoperative week there was progressive rise in pressure indices, reaching statistical significance on day 6, though with greatest rise on day 1. Although preoperative ABI less than 0.4 and TBI less than 0.1 were associated with high occlusion risk, the specificity of these indices was too low for predictive value. The repeated measurements during postoperative week 1 added no useful information to that obtained on day 1.

Aged↗

Immunohistochemical localization of plasminogen activators in human saphenous veins.

Human saphenous veins were analyzed for presence of plasminogen activators (t-PA) in the endothelium of the vessel walls by immunohistochemical techniques. We used a polyclonal rabbit antihuman t-PA antibody, a monoclonal mouse-antihuman t-PA and a goat antibody to low molecular weight urokinase. To demonstrate presence of antigen we used FITC conjugated anti-IgG or the Biotin-Avidin technique. Both monoclonal and polyclonal anti-t-PA demonstrated positive fluorescence in the endothelial layer. Tests for urokinase were negative. The present study thus demonstrated that t-PA was present in the vascular endothelium. This is in accordance with data from earlier histochemical studies for detection of PA activity.

Endothelium↗

Low molecular weight heparin once daily compared with conventional low-dose heparin twice daily. A prospective double-blind multicentre trial on prevention of postoperative thrombosis.

In a randomized, prospective, double-blind multicentre trial, the effect of conventional low-dose heparin 5000 units twice daily, was compared with that of a low molecular weight heparin fragment (4000-5000) 5000 anti-factor Xa units once daily. Four hundred and thirty-two patients fulfilled the inclusion criteria and were analysed for development of deep vein thrombosis (125I-labelled fibrinogen test) and haemorrhagic complications. Thrombosis occurred in a 4.3 per cent of patients in the low-dose heparin group and in 6.4 per cent of patients in the heparin fragment group, a difference which is not significant. There was a significant delay in the onset of thrombosis in the heparin fragment group. Mortality did not differ between the groups, nor did peroperative blood loss or transfusion requirements or infectious complications. Haemorrhagic complications occurred significantly more often in the fragment group (11.6 per cent) than in the conventional heparin group (4.6 per cent). Patients in the heparin fragment group experienced local pain following the subcutaneous injection significantly less often.

Adult↗

A comparison of static cytofluorometry and flow cytometry for the estimation of ploidy and DNA replication in human breast cancer.

332 primary invasive breast carcinomas were analysed by static cytofluorometry and flow cytometry. The ploidy distributions were similar, and 54% of the tumors were judged DNA aneuploid by both methods. The coefficient of variation of the G0-G1 peaks ranged from 2.0 to 8% with both techniques, but the mean was somewhat lower with flow cytometry--4.1%, compared to 4.9% for the static measurements. The proportion of S-phase cells was possible to estimate from 80% of the flow histograms and 70% of the static histograms. S-phase was not estimated from the static histograms if less than 150 tumor cells were measured. With 160 tumors S-phase was measured by both methods. The range was 0 to 27% with the static measurements and 0.7 to 25% with flow cytometry. Corresponding mean values were 7.6% and 8.2%, which are similar to thymidine labeling index results with breast cancers reported in some studies. A close correlation was obtained (r = 0.927) comparing S-phase fractions estimated from aneuploid tumors with flow cytometry and static cytofluorometry if more than 200 cells were measured with the latter. The proportion of S-phase cells was significantly lower for the diploid tumors. We conclude that both techniques can be useful for the estimation of DNA ploidy and replication in human breast cancer.

Aneuploidy↗

Extravascular lung water measurement in septic sheep.

Sheep were prepared with a chronic lung lymph fistula and studied unanesthetized following septicemia by infusion of live Escherichia coli 10(9) ml/kg bw or injection of oleic acid 0.05 ml/kg bw. Extravascular lung water (EVTV) was measured with thermal-dye technique and compared to gravimetrically measured lung water (EVWV). Septic sheep had increased pulmonary artery pressure, reduced mean arterial blood pressure and reduced cardiac output. In control animals there was a correlation between EVTV-EVWV of r = 0.70. In animals given oleic acid lungs were macroscopically edematous and the correlation was r = 0.93. In septic sheep, however, no correlation could be found between EVTV and EVWV (r = -0.25). The thermal-dye technique was found to give erroneously high values. This finding could probably be due to erythrostasis and leukocyte plugging with uneven perfusion and prolonged transit times due to reduced cardiac output.

Animals↗

DNA-measurements on formalin-fixed, paraffin-embedded squamous cell carcinomas from different ENT-regions.

DNA measurements were performed on formalin-fixed, paraffin-embedded squamous cell carcinomas, using the method of Hedley et al. Ultrasonication was sometimes necessary after enzymatic disintegration to dispose of residual cytoplasm. The isolated nuclei were stained with Hoechst 33258. DNA measurements were performed using a rapid system for static fluorometry (FLUORA-programme). The method proved to be highly accurate. The mean CV of the stem cell peaks from different tumours was 5.3. There was no difference between material less or more than 5 years old (mean CVs 5.2 and 5.5 respectively). RNase treatment had no effect and was therefore not considered necessary. The proliferative activity was calculated by computer assuming a rectilinear distribution of S-phase cells. Because routinely paraffin-embedded material can be used, DNA analysis can be performed on tumour material where the clinical outcome is known, in order to evaluate certain DNA variables.

Carcinoma, Squamous Cell↗

DNA measurement--an objective predictor of response to irradiation? A review of 24 squamous cell carcinomas of the oral cavity.

DNA measurements on biopsy material from 24 squamous cell carcinomas of the oral cavity given preoperative radiotherapy indicate that DNA aneuploid tumours respond better to radiotherapy than do diploid and polyploid tumours. The mean S-phase value was higher (16.1%) for 8 tumours that were eradicated by preoperative radiotherapy than for 13 that did not respond (8.1%). These factors correlated better with the response than did histological and clinical (T) classifications. DNA-ploidy and S-phase estimation can complement the histological diagnosis, and may prove valuable when planning treatment.

Carcinoma, Squamous Cell↗

Early activation of humoral proteolytic systems in patients with multiple trauma.

Coagulation, fibrinolytic, kallikrein, and complement systems were studied in 20 patients with multiple trauma. Three of four patients with a trauma score less than 10 on hospital arrival died, compared to one of 16 with a score over 10. Five patients developed disseminated intravascular coagulation. Signs of activated cascade systems were evident in most patients on hospital arrival. Changes were not related to trauma score, but patients with an arterial pressure below 110 mm Hg had significantly lower levels of antithrombin III and alpha 2-antiplasmin than those with higher BP. This study confirms that the cascade systems are activated very soon after multiple trauma.

Adolescent↗

Prospective double-blind comparison between Fragmin and conventional low-dose heparin: thromboprophylactic effect and bleeding complications.

In a randomized, prospective, double-blind multicenter trial, the effect of low-dose conventional heparin (5,000 IU/12 h) was compared to a low molecular weight (LMW) heparin fragment (5,000 antifactor Xa U/24 h). 432 patients 40 years or older undergoing elective abdominal surgery were included, 382 correctly treated. 45% had malignant diseases. The groups did not differ in risk factors. Analysis was made both on the basis of intention to treat and correct prophylaxis. No difference in results between these 2 groups was seen. Deep vein thrombosis (125I-fibrinogen) occurred in 4.3% of the low-dose heparin group and in 6.4 of the LMW heparin group. There was a significant delay in the onset of deep vein thrombosis in the LMW heparin group. Mortality, peroperative blood loss, transfusions or infectious complications did not differ. Hemorrhagic complications occurred significantly more often in the LMW heparin group (11.6%) than in the low-dose heparin group (4.6%). Significantly fewer patients experienced local injection pain in the LMW heparin group. APTT and AT III were similar in both groups, but anti-Xa activity was significantly higher in the LMW heparin group. Single daily LMW heparin injection reduced the frequency of deep vein thrombosis to the same level as low-dose heparin twice daily. The dose or administration interval of LMW heparin in this study caused significantly more bleeding complications.

Aged↗

The pulmonary microvascular response to infusion of live Escherichia coli in sheep with acutely or chronically prepared lung lymph fistula.

The effects of infusion of live Escherichia coli bacteria in awake sheep with a chronic lung lymph fistula (n = 15) were compared to anesthetized animals (n = 7) receiving the same septic insult after surgical trauma including bilateral thoracotomies for lung lymph cannulation (acute group). During preseptic baseline conditions, pulmonary arterial pressure (Ppa) and central venous pressure (Pcv) were increased and leukocytes decreased in the newly operated animals compared to the sheep with a chronic lung lymph fistula. After i.v. infusion of live E. coli 10(9) X kg-1 b.w. over 20 min, arterial pressure (Psa), cardiac output (Qt), leukocytes, and partial pressure of arterial oxygen (PaO2) decreased in both groups. Ppa peaked after 15 min at 37.2 +/- 2.5 in the chronic and 33.4 +/- 3.3 mm Hg in the acute group. In the chronic group, Ppa remained elevated but not in the acute group during the rest of experiment. Lung lymph flow (QL) increased significantly in both groups during the initial high Ppa, but it increased to a higher level in the chronic group. After 150 min, QL did not differ between the groups but remained elevated over baseline. Lymph-to-plasma concentration ratio (L/P) for total protein decreased in the chronic group during the initial high QL. This decrease was not seen in the acute group that had a significantly higher L/P between 30 and 120 min after sepsis. The high QL with unchanged L/P compared to baseline indicated increased permeability in the pulmonary microvessels in both groups but the changes in permeability, hemodynamics, or respiratory parameters after sepsis were not aggravated by the surgical trauma.

Acute Disease↗

Endothelial surface ultrastructure following hypoxia and hyperoxia.

Effects of hypoxia and hyperoxia on the ultrastructure of aortic endothelial cells were studied in rats. Rats were subjected to FIO2 0.05, 0.06 or 0.1 for various period times. Hypoxia was followed by nuclei protrusion, appearance of holes through the luminal membranes of individual cells. Some cells showed signs of partial of total disintegration. Hyperoxia (FIO2 = 1.0) were followed by slight morphological changes notable after 8 hours but most pronounced after 24 hours. The present study corroborated previous studies in that both hypoxia and hyperoxia can alter endothelial integrity.

Animals↗