Biomedical subjects
Publications and source records attributed to B Risberg.
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Welding fume contains various metals and pulmonary effects from their inhalation are largely unknown. We have studied the effects of exposure to welding fume in sheep. The animals were exposed to either a bolus dose of welding fume solution or to five weeks daily exposure. Lung physiology parameters were studied and biopsies taken. Magnetopneumography was used to register the longterm exposure. Acutely exposed animals had elevated pulmonary arterial pressure. Arterial oxygen tension was reduced after fume instillation. These animals had accumulation of iron (Fe), magnesium (Mg) and manganese (Mn) in the lungs. Mn was elevated 40 times. Longterm exposed sheep increased the iron oxide accumulation significantly in lungs as seen with the magnetopneumographic technique. Following long term exposure, Mn was the metal most heavily retained in the lungs. Metals like Mn, Fe and Mg retained in the lungs can possibly give negative health effects. Besides this, the metals could be used for quantitation of welding fume exposure.
In this study we have compared two different preparation methods for DNA flow cytometry on breast cancer. Tumour cell suspensions from 49 breast cancers were analysed on a Facscan flow cytometer. In seven of 49 cases, additional aneuploid peaks were found after enzyme/detergent treatment (E/D), not seen after the detergent (D) preparation. S-Phase fractions were significantly higher after D than after E/D preparation (mean values, 15 and 8%, respectively), although the correlation was high between the two methods. S-Phase fraction estimated after background correction diminished the differences between the two methods (mean values, 8 and 6%). Furthermore, the fraction of G2/M cells were generally greater with the D method. These differences can be explained by increased number of cell doublets and nuclear fragments after D compared to E/D preparation. This clearly shows that the preparation method influences the result of DNA flow cytometry on human breast cancers.
To study the effects of standardized mental stress (arithmetic and the Stroop color word test) on plasma coagulation and fibrinolysis, blood samples were obtained before, during, and after 20 minutes of mental stress from 10 healthy, non-smoking young males aged 22 to 30 years. Reactions were compared with those observed during physical exercise and infusion of adrenaline. Both von Willebrand factor antigen and factor VIII coagulant activity increased significantly in response to mental stress (95 +/- 28 vs 123 +/- 56%; p less than 0.05 and 125 +/- 54 vs 217 +/- 170%; p less than 0.05, respectively). There was also a significant increase of factor VII coagulant activity (86 +/- 31 vs 108 +/- 51%; p less than 0.05). Furthermore, mental stress caused an activation of the fibrinolytic system with an elevation of tissue plasminogen activator activity and tissue plasminogen activator antigen (0.80 +/- 0.48 vs 1.23 +/- 0.96 IU/ml; p = 0.076 and 4.38 +/- 1.87 vs 5.78 +/- 2.58 IU/ml; p less than 0.01). Fibrinogen concentration increased during stress (1.95 +/- 0.29 vs 2.11 +/- 0.27 g/l; p less than 0.05). Similar but more pronounced responses were observed during exercise and adrenaline infusion. Parallel to the increases in coagulation and fibrinolytic factors there were significant increases in heart rate, and systolic and diastolic blood pressure. It is concluded that mental stress has significant effects on plasma coagulation and fibrinolysis, and that it could thus affect important risk factors for cardiovascular disease.
Blood collected in different anticoagulant/antiplatelet agents (ETP, EDTA, citrate, citrate/citric acid pH 4.5 and CTAD) was compared with respect to determination of PAI-1 activity and PAI-1 antigen. beta TG and PF4 were analysed as markers of platelet release. Both the middle layer and the remaining layer of the plasma were studied. Moreover vWF:Ag, FVII:Ag, ECLT, t-PA:Ag, t-PA activity, APTT, VIII:C and VII:C were assayed in blood collected in citrate and CTAD. PAI-1 activity showed the same level in all citrate based anticoagulants and ETP and no increase was found in blood standing for 2 hours at room temperature. On the contrary quick handling was most important for determination of PAI-1 antigen. In tubes anticoagulated with citrate no significant increase was found if the sample was prepared within 1 hour. EDTA was not suitable as anticoagulant mixture. Tubes containing the antiplatelet mixture CTAD could be used for determination of PAI activity, PAI antigen, vWF:Ag, FVII:Ag, t-PA activity and APTT. For measurement of PAI-1 antigen quick handling of blood anticoagulated with antiplatelet mixtures are preferable, and plasma treated in that manner could also be used to assay some hemostasis parameters.
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Paraffin-embedded curettage material from 120 patients with stage I and II endometrial cancer were analyzed by flow cytometry. The follow-up time in all cases was at least 5 years or until death. It was possible to determine DNA ploidy in 111 cases and S-phase was also evaluated in 92/111 cases. DNA ploidy and S-phase were then compared with the FIGO grading and clinical outcome. DNA ploidy results showed that 11% of grade 1 tumors were aneuploid, 14% of grade 2, 42% of grade 3, and 85% of the cases of uterine papillary serous carcinoma (UPSC) were aneuploid. Patients with tumors that showed an S-phase fraction below 5% had a cumulative 5-year cancer mortality of 7% whereas 49% of the patients with tumors having S-phase fraction above 10% died of their cancer. The prognostic significance of DNA and S-phase correlated fairly well with the FIGO grading as determined by a pathologist with special interest in gynecologic oncology and the DNA parameters added prognostic information independent of the FIGO grading.
Adenoid cystic carcinoma (ACC) is a slow-growing tumor with a marked tendency for perineural and local invasion. The neoplasm occurs more frequently in the head and neck region and only 39 previously described cases of adenoid cystic carcinoma of Bartholin's gland are found in the world literature. Most authors advocate surgery as the primary treatment. Several cytostatic drugs have been tried but the results have been poor. The benefit of radiotherapy in the treatment of this type of tumor is not yet established. This is a report of five new cases all treated with surgery and postoperative radiotherapy. Three patients had histopathologically proven evidence of residual disease after surgery and were subsequently treated with radiotherapy. They are now living without evidence of disease after 28, 51, and 138 months.
Intracavitary irradiation was administered to 366 patients with endometrial carcinoma stage I by a high dose-rate afterloading method using 60Co sources (bulb technique). In 275 cases hysterectomy and bilateral salpingo-oophorectomy were performed 6 weeks later and in 91 cases dilation and curettage was used to verify tumor eradication. In 58% of the hysterectomy specimens no residual carcinoma was detected at the histopathologic evaluation. In the group treated with radiotherapy alone 74% showed no carcinoma remnants in the curettings 3 months after therapy. The effect of the fractionation dose was evaluated in relation to the outcome of the histopathologic examination. The proportion of specimens with no residual carcinoma increased from 27% for the 5 Gy per fraction group to 78% for the 10 Gy per fraction group. Recurrences were recorded in 13% in the hysterectomy group and in 29% in the group treated with radiotherapy alone. The 5-year corrected survival rate for the combination-treated group was 88% and for the group treated with radiotherapy alone 72%. If the dose per fraction is specified in the range of 5 to 8 Gy the high dose-rate afterloading technique seems safe with a tumor control rate and a frequency of radiation reactions comparable to the manual radium method.
Local trauma to the lungs induces a temporary permeability disturbance with reduction in the osmotic reflection coefficient of a sheep lung lymph model. Proteolytic enzymes may be involved in this microvascular injury. In the present study, we tested the hypothesis that pretreatment with methylprednisolone prevents activation of proteolytic systems after pulmonary trauma and that these systems are of etiological importance in the development of the pulmonary lesion. Central markers of proteolytic cascade systems were monitored in sheep subjected to local trauma to the lungs (lung lymph fistula preparation) with (n = 7) or without (n = 7) methylprednisolone (30 mg/kg) pretreatment. In control animals, reduced levels of prothrombin, antithrombin, kallikrein inhibitors, antiplasmin, and increased level of plasminogen activator inhibitor (PAI) indicated systemic activation of the coagulation, kallikrein-kinin, and fibrinolytic systems. These changes, except for PAI, were more pronounced in lung lymph. High levels of thromboxane A2 and 6-keto prostaglandin F1 alpha were found in lymph. In steroid-pretreated animals, the prostanoid response was attenuated, but all other variables were similar to control animals; thus, steroids did not prevent either local or systemic proteolytic enzyme activation caused by local trauma to the lung. The etiological role of this activation in the development of lung lesion has not yet been evaluated.
The effect of septicemia on the elimination of hyaluronan (HA) from the lung interstitium was investigated in awake sheep with chronic lung lymph and thoracic duct fistulas. The result was compared with that after elevation of left atrial pressure (LAP). Lymph was sampled before and after a 20-min infusion of Escherichia coli (10(9) bacteria/kg body wt.), after elevation of LAP, or both. Infusion of E. coli caused an increased flux of HA in lung lymph and thoracic duct lymph. After an elevation of LAP, the HA flux in lung lymph was increased to a comparable extent. In animals subjected to an increase in LAP and subsequently to infusion of E. coli, no additive effect on HA flux was seen. The weight-average molecular weight of HA in lung lymph was increased both after sepsis and after elevation of LAP. The findings show that sepsis and elevated transvascular hydrostatic pressure result in increased mobilization of HA from the interstitium. This might partly explain the increased HA concentrations in plasma in clinical sepsis and may also lead to a change in the characteristics of the interstitial matrix in this condition.
Changes in pulmonary microvascular permeability in sheep, after oleic acid injection, were studied using estimations of the osmotic reflection coefficient (sigma d) for total protein, albumin, immunoglobulins (Ig) G and M and calculation of the equivalent small and large pores of the microvessels. A chronic lung fistula was prepared in eight sheep. After a base-line period, left atrial pressure (Pla) was increased. Oleic acid (0.05 mg/kg body wt) was injected after a filtration-independent state had been obtained, and the spontaneously ventilating animals were then followed for 2 h. The sigma d for the normal lung was 0.65 +/- 0.03, 0.59 +/- 0.02, 0.72 +/- 0.04, and 0.84 +/- 0.02 for total protein, albumin, IgG, and IgM, respectively. The equivalent pore radii were 54 and 225 A. After oleic acid infusion, arterial pressure and arterial O2 tension decreased and leukocytes and platelets were consumed. At the end of the experiment, sigma d's were 0.27 +/- 0.04, 0.24 +/- 0.07, 0.33 +/- 0.06, and 0.55 +/- 0.04 for total protein, albumin, IgG, and IgM, respectively. The equivalent pore radii were 54 and 275 A, and the number of large pores was increased by 195%. The results indicate that oleic acid produces an increased vascular permeability by increasing the size and the numbers of large pores of the pulmonary microvascular walls.
278 patients with either stage I or II endometrial carcinoma treated between January 1979 and January 1982 were reviewed, particularly as regards certain prognostic factors. Uterine papillary serous carcinoma (UPSC), FIGO grade 3, nuclear grade 3, and age were the major independent prognostic factors. UPSC was diagnosed in 8% of the patients. The cancer mortality in the non-UPSC group was 7%, vs. 41% in the UPSC group. In the latter group all the deaths occurred within 2 1/2 years. Poorly differentiated non-UPSC had the same cancer death rate as UPSC, but usually had a completely different histological pattern. There was no significant difference in survival between stage I and stage II when corrected for FIGO grade and nuclear grade.
Preoperative intracavitary irradiation was administered to 366 patients with endometrial carcinoma stage I by a high dose rate afterloading method using 60Co sources (bulb-technique). In 275 cases hysterectomy and bilateral salpingo-oophorectomy were performed 6 weeks later and in 91 cases dilation and curettage was used to verify tumor eradication. In 58% of the hysterectomy specimens no residual carcinoma was detected at the histopathologic evaluation. In the group treated with radiotherapy alone 74% showed no carcinoma remnants in the curettings 3 months after therapy. The effect of the fractionation dose was evaluated in relation to the outcome of the histopathologic examination of the hysterectomy and curettage specimens. The proportion of specimens with no residual carcinoma increased from 27% for the 5 Gy per fraction group to 78% for the 10 Gy per fraction group. Recurrences were recorded in 13% in the hysterectomy group and in 29% in the group treated with radiotherapy alone. The nuclear grade of the tumor and the age of the patient were the most important risk factors for tumor recurrence. The 5-year crude survival rate for the combination-treated group was 84% and for the group treated with radiotherapy alone 47%. The corresponding corrected survival rates were 88 and 72% respectively. Serious late radiation reactions were noted in 6.6%. The significant risk factors for radiation reactions were dose per fraction and the age of the patient.
The nuclear DNA contents of tumor cells in 73 patients with endocrine gastrointestinal tumors, 19 patients with endocrine pancreatic tumors (EPT) and 54 patients with malignant carcinoid tumors were determined before and after treatment. The DNA profiles were divided into diploid and aneuploid. In untreated patients, 9 out of 10 (90%) primary EPT and all 9 primary malignant carcinoid tumors (100%) were diploid. Tumor cell imprints from liver metastases of patients with untreated EPT showed aneuploidy in 5 of 11 cases, but only in 7 out of 46 DNA records from patients with untreated carcinoid liver metastases. DNA alteration from diploid to aneuploid profiles occurred in 2 patients with endocrine pancreatic tumors who had received chemotherapy. A change from diploid to aneuploid records was also seen in 7/23 (30%) carcinoid tumors after treatment. The DNA patterns before and after treatment did not show any correlation with survival or treatment response.
Twenty-nine patients were operated on with the Charnley hip prosthesis. All the patients were given dextran 70 as thrombosis prophylaxis. Deep vein thrombosis (DVT) was diagnosed in 10 patients with the radioactive fibrinogen uptake test and phlebography. Variables of coagulation and fibrinolysis were studied before and after surgery. Tissue plasminogen activator (t-PA) activity in the plasma without venous occlusion decreased postoperatively, but there was no correlation with DVT. The t-PA activity in venous occlusion plasma was not reduced after surgery. Plasminogen activator inhibitor (PAI-1) levels were raised immediately postoperatively. There was a significant correlation between preoperative PAI-1 activity and development of postoperative DVT (P less than 0.05). Patients developing DVT had higher levels of PAI-1 postoperatively than patients not developing DVT. A defective fibrinolytic system, as defined by high PAI-1 activity, thus predisposed to postoperative DVT.
Surgical preparation of a lung lymph fistula in sheep was previously shown to induce temporary permeability disturbance of pulmonary microvessels. Flow and composition of lung lymph were compared in 19 sheep with acute, and 16 with chronic lymph fistula. Lymph and plasma were analyzed regarding activities of prothrombin, antithrombin III, prekallikrein, kallikrein, functional kallikrein inhibitors and 11 acid hydrolases of lysosomal origin. Levels of prothrombin and antithrombin III fell postoperatively in plasma and reached even lower values in lymph, indicating systemic activation of the coagulation system as well as local activation in the lung. The studied components of the plasma-kallikrein system were unchanged. Lysosomal enzymes were released in lung lymph, reflecting cell injury in the lung. Local activation of proteolytic enzyme systems thus occurs in the lung after trauma. Analysis of organ-specific lymph (= interstitial fluid) may contribute to better understanding of the pathophysiology of trauma.
The first section of this review describes the hemostatic balance as it is regulated at the blood-tissue interface. Endothelial cells have a nonthrombogenic surface during resting conditions. In diseased states, such as trauma or infection, the endothelial cells become perturbated and the anticoagulant activity is transformed into a procoagulant activity. Recent data have demonstrated that endothelial cells have surface receptors and the capacity for initiating coagulation and propagating the coagulation cascade. The second part of this review discusses the role of the fibrinolytic system in thromboembolism. Defects in the system have been found to be pathogenetic factors in postoperative deep vein thrombosis. Several studies have indicated that this surgical sequela does not occur in patients with an active fibrinolytic system. These results suggest that screening patients for fibrinolytic abnormalities may identify those persons at high risk for the development of postoperative deep vein thrombosis.