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Granulosa and theca cell tumors of the ovary account for 2-3% of ovarian malignancies. This study includes 54 patients with the diagnosis of granulosa cell tumors of the ovary treated between 1953 and 1987. Median age at diagnosis was 57 (27-83) years. The lesions were staged according to FIGO. The number of patients in various stages was IA, 41; IB, 3; IC, 3; IIB, 6; and III, 1. Median tumor size, 11 cm; range, 0.5-30 cm. Post-menopausal bleeding was diagnosed in 48%, MHC in 37%, proliferative endometrium in 32%, and atypia of endometrial cells in 13% of the cases. Fifty patients were treated with primary surgery, 48 patients were treated with adjuvant external radiotherapy, and 3 patients received complementary chemotherapy. The survival rates in stage I were 94 and 88% after 5 and 10 years, respectively, and in stages II-III were 44% after 5 and 10 years. Overall survival was 90% at 5 years. The frequency of observed mitosis influenced the survival rate: with less or equal 4/10 HPF the survival was 100% in 5 years, with 5-9/10 HPF the survival was 80% in 5 years with a median survival time of 9 years, and with more or equal 10/10 HPF the longest survival was 4 years. At the end of the study, 45 patients (83%) are alive with no evidence of disease, 1 patient is alive with disease, 4 patients are dead of recurrent disease, and 4 patients are dead from intercurrent disease. Endometrial carcinoma was detected in 5 patients. The total survival is better than that with epithelial ovarian cancer as the hormonal symptoms make an early diagnosis possible. Stage for stage the survival is equal. There is an increased incidence of endometrial carcinoma and concomitant other malignancies. The mitotic rate is a well-defined parameter and influences the survival significantly and should be considered the most important prognostic factor at treatment planning.

In order to study interinstitutional reproducibility of flow cytometric DNA-analysis (DNA-FCM), frozen pieces from 30 consecutive breast carcinomas were analysed by 5 laboratories. Different instruments, preparation and DNA staining methods were used. A concordance in DNA-ploidy status was obtained in 26 of the 30 tumours. The discrepancy can mainly be explained by intratumoural DNA-heterogeneity since a complete agreement in ploidy status was obtained when four of the laboratories analysed the same cell suspension, where solid bits showed differing results. The sampling method seems therefore to be a crucial step for the results and needs further studies. As far as the estimation of S-phase fraction was concerned, one laboratory obtained significantly higher values compared to the other four. The correlation between the other four laboratories varied between r = 0.66-0.92.

Postoperative formation of adhesions is a common complication in abdominal surgery. The aim of the present study was to develop standardized experimental models for quantitative studies of the formation of adhesions in rats and rabbits. In rats the suturing of a peritoneal wound increased adhesion formation significantly compared to leaving it open, 77.9 +/- 4.8 and 5.3 +/- 2.8%, respectively (p < 0.001). The suturing technique, when comparing the interrupted and continuous method after 1 week, had no influence, 84.5 +/- 6.3% and 73.1 +/- 11.2%, respectively (p > 0.05). Different types of trauma resulted in differences in adhesion formation to noninjured parts in the abdominal cavity, adhesions in 17.5 and 2.5% of the animals, respectively (p < 0.05). In rabbits adhesions formed more frequently (p < 0.001) to visceral peritoneum (59.3 +/- 3.7%) than to the parietal one (22.3 +/- 1.6%) indicating a different propensity of tissues to have adhesions. These models enable detailed quantitative studies on experimental formation of adhesions.

The rat gastric mucosa, superfused with 0.1 N HCl, was investigated following 15 min of hemorrhagic shock and 30 min of retransfusion after pretreatment with ascorbate (1 mg/100 g b.w. or 5 mg/100 g b.w.). The size of the ischemic areas and the amount of mucosal bleeding using 51Cr labeling of red blood cells were assessed. Ischemic areas developed during shock. Following retransfusion, bleedings occurred at the border zones between ischemic and surrounding circulated areas. Ascorbate in both doses protected the gastric mucosa by reducing the amount of bleeding following 30 min of retransfusion as well as by reducing the area of ischemia 5 min after retransfusion.

Complement and fibrinolytic factors were measured in 9 infants undergoing hemofiltration immediately after cardiopulmonary bypass in an attempt to reduce activation of these systems. Plasma levels of C3a, C5a, and terminal complement complexes increased during bypass by 460%, 85%, and 745%. Plasma levels were reduced after hemofiltration in 8 of the 9 infants, and C3a and C5a fractions were recovered in the ultrafiltrate. The observed activation of the fibrinolytic system seemed to be unaltered by hemofiltration. Fibrinolytic factors were not filtered. Our study shows that increased concentrations of complement factors in the plasma after bypass in infants may be reduced by hemofiltration.

Tissue plasminogen activator (t-PA) is a marker of endothelial cell injury or activation. The release of t-PA from isolated rat hearts (Langendorff model) subjected to ischemia-reperfusion or reactive oxygen intermediates (ROI) generated by H2O2 was investigated. H2O2 (200 microM) increased t-PA activity in the coronary effluent to 305 +/- 84% of initial value (mean +/- SEM, p < 0.04 vs controls) at the end of a 10 min intervention. The hydroxyl radical scavenger thiourea (10 mM) only partially inhibited the increase (175 +/- 27%, p < 0.01 compared to controls). 20 min normothermic ischemia increased t-PA activity to 416 +/- 108% (p < 0.005 compared to controls) at the start of reperfusion. In conclusion, cardiac injury by ischemia-reperfusion or ROI increases release of t-PA.

The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric mucosal microcirculation and purine nucleotide metabolism were studied after hemorrhagic shock and retransfusion in rats. The number of perfused microvessels and the concentration of adenosine triphosphate, adenosine monophosphate, inosine monophosphate, inosine, hypoxanthine, xanthine, and uric acid were investigated in mucosal biopsy specimens after 15 or 45 min of hemorrhagic shock and after 15 min of shock followed by 30 min of retransfusion. During shock a dephosphorylation of nucleotides and a decrease in the number of perfused microvessels occurred, the more the longer the duration of the shock period. Retransfusion led to an additional reduction in the number of perfused microvessels, but there was a partial restoration of high-energy phosphate metabolites in those areas of the mucosa which maintained a blood flow. The results indicate that there is a renewal of energy stores in gastric mucosa after hemorrhagic shock and reperfusion, although parts of the vascular bed are not reperfused.

An earlier study of perfused rat lungs showed that leukocytes, given as bolus injections, seemed to become more or less permanently trapped in the pulmonary microvascular bed under erythrocyte-free perfusion. The aim of the present study was, therefore, to investigate the rheologic effects of erythrocytes on the leukocyte microcirculation of perfused rat lungs. Leukocyte and erythrocyte suspensions were given as bolus injections during cell-free, constant pressure perfusion of ventilated rat lungs. Leukocyte numbers were counted in samples of the venous effluent and flow resistance changes were computed from registrations of flow rate, arterial and venous pressures. The preparations showed a continuous efflux of leukocytes which had been trapped in the pulmonary microcirculation before the perfusion was started. A bolus infusion of erythrocytes (3 ml, hematocrit: 30%) caused a transient flow resistance increase during the passage of the erythrocyte bolus through the vascular bed. This initial peak was accompanied by an increased venous efflux of leukocytes and followed by a lower second peak, attributed to a redistribution of trapped leukocytes in the capillary bed. Infusions of mixed cell suspensions (20-30 x 10(6) leukocytes in 30% hematocrit) caused a transient resistance increase similar to that caused by erythrocytes and a sustained resistance increase, less persistent than that caused by leukocytes. The present data suggest that the infusion of erythrocytes caused a re-distribution and an increased efflux of leukocytes, pooled in the pulmonary microcirculation. The rheological effects of erythrocytes could, hypothetically, result from mechanical interactions with the leukocytes in the pulmonary microvessels.

The efficacy of transdermal norethisterone acetate in sequence with transdermal estradiol has been investigated in a multicenter study of 136 post-menopausal women to determine the incidence of endometrial hyperplasia, the effects on the vaginal cytology and the control of bleeding. Treatment consisted of 12 cycles of 4 weeks each (2 weeks estradiol 50 micrograms/day followed by 2 weeks of a new combined patch delivering norethisterone acetate 0.25 mg/day and estradiol 50 micrograms/day). Endometrial histology was assessed by two pathologists. Of the 136 pre-treatment biopsies 89% provided no material, an inadequate sample or an inactive (atrophic or non-secretory) endometrium. Of the post-treatment biopsies from 110 women who completed the study: 65% showed secretory, 3% proliferative and 24% inadequate material or inactive endometrium. Hyperplasia was found in two biopsies (2%); in one of these focal atypical hyperplasia was agreed by both pathologists, in another a hyperplastic endometrial polyp was diagnosed by one pathologist. The bleeding was regular in 80% of the 1195 cycles and irregular in 11%. No bleeding occurred in 9% of the cycles. Vaginal cytology showed a significant shift towards increased maturation during treatment.

Nuclear morphometry was performed on the diagnostic biopsy in 65 cases of non-mucinous ovarian carcinoma (FIGO stage IIB-IV) and its prognostic value regarding patient survival after the second-look operation was compared to that of morphology and clinical observations. In a univariate Cox survival analysis four morphometric factors were found to be significant predictors of survival (the standard deviations (SD) of the nuclear area, perimeter, largest perpendicular axis, and largest axis). Age, the size of residual tumor after the primary operation, and a combined variable describing the status at the second-look operation and also the result of tumor reduction were significant clinical variables. None of the morphologic variables proved to be significant. In the multivariate Cox analysis the SD of the largest perpendicular nuclear axis gave independent prognostic information together with either the size of residual tumor after the primary laparotomy (P = 0.00004) or the second-look variable (P < 0.00001). When the SD of the largest perpendicular nuclear axis and the second-look variables were included in the model the size of residual tumor after the primary operation added no further prognostic information. We conclude that nuclear morphometry is a simple, easily implemented and cheap quantitative method which gives objective and valuable prognostic information regarding survival in advanced ovarian cancer.

The Kensey dynamic angioplasty catheter is an instrument for mechanical intravascular atherectomy using a rotating cam to recanalize occluded arteries. Twelve dynamic angioplasties were performed in 11 patients. The procedure was followed by an additional balloon dilatation in all cases. A technical success, i.e., a restored lumen, was recorded in 7 patients but only 4 had a functional improvement. No distal embolization or other serious complication occurred. This preliminary report shows that the therapeutic potential with this technique must be further investigated.

To study the effect of sex hormones on the hemostatic responses to stress, blood samples were collected before, during, and after 20 min of mental stress from 9 healthy, non-smoking female volunteers, examined in the follicular and luteal phase. Mental stress caused significant increases in heart rate, blood pressure, and plasma catecholamines. In addition, analysis of variance indicated significant changes of leukocyte count, hematocrit, fibrinogen, von Willebrand factor antigen, t-PA activity and antigen in response to the stress test. However, in contrast to a male group previously investigated, there were no significant changes in factor VII coagulant activity in either menstrual phase. Overall the responses were more pronounced in the luteal as compared to the follicular phase. The findings support the concept that both gender and physiological variations in female sex hormones may modulate hemostatic responses to psychosocial stress.

Intravital fluorescence microscopy and morphometry were used to study the microcirculation in the rat gastric mucosa during and after hemorrhagic shock. Under control conditions the circulation appeared homogeneous and unaffected by superfusion with 0.1 N HCl. During hemorrhagic shock, scattered areas of the mucosa lost circulation. Morphometry showed that the number of perfused mucosal vessels decreased significantly in the abluminal part of the mucosa both in perfused and ischemic areas, the reduction being most pronounced in the ischemic areas, where the number of perfused luminal vessels also decreased significantly. During reperfusion, bleedings occurred from the mucosa. A key finding was that the bleedings always had their origin at the border zone between ischemic and perfused areas. After hemorrhagic shock adenosine triphosphate and energy charge levels dropped significantly in both perfused and ischemic areas but with significantly lower levels in the ischemic areas. The hypoxanthine levels increased in both perfused and ischemic areas. The experiments show that local mucosal ischemia and accelerated nucleotide degradation are of pathogenetic importance in the development of stress ulcers after hemorrhagic shock. The border zone between circulated and ischemic areas seems to be an area of special interest.

The local effect of operative trauma on the fibrinolytic system was studied in ten patients undergoing total hip replacement. Catheters were inserted in the femoral veins on both sides and blood was sampled from these catheters perioperatively. The following fibrinolytic variables were analysed in plasma and related to the different steps of surgery: tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI-1) activity. During surgery PAI-1 activity and t-PA antigen in the operated limb were significantly increased compared with preoperative values. There was a significant difference in PAI-1 activity and t-PA antigen between the operated and the non-operated limbs during surgery and within one hour postoperatively. During fixation of the femoral implant there was a significant difference between the operated and the non-operated limbs in t-PA activity. Thus the regional fibrinolytic response to trauma was dissociated from the response in the non-operated limb. The clinical relevance of the observed alterations in regional fibrinolysis, as related to thrombogenic mechanisms after hip surgery, remains to be elucidated.

The incidence of deep vein thrombosis (DVT) and pulmonary embolism was studied prospectively in patients undergoing elective total hip replacement. 96 patients were randomly allocated to receive either low molecular weight heparin (LMWH) or unfractionated heparin (UFH). All patients had bilateral phlebography and pulmonary perfusion/ventilation scintigraphy 10-12 days after surgery. The following fibrinolytic variables were analysed in plasma and related to thromboembolism: tissue plasminogen activator (t-PA) activity, t-PA antigen (t-PA Ag), plasminogen activator inhibitor (PAI-1) activity and PAI-1 antigen (PAI-1 Ag). No significant difference was found, regarding the fibrinolytic response to surgery, between patients treated with LMWH and UFH. The level of PAI-1 activity was significantly increased before operation in patients developing DVT as compared to non-DVT patients (p less than 0.03). Immediately after surgery and in the morning the first postoperative day the levels of PAI-1 activity, PAI-1 Ag and t-PA Ag were positively correlated to thromboembolism. PAI-1 activity was the only preoperative fibrinolytic variable correlated to thromboembolism.

In a prospective, randomized, double-blind study, the efficacy and safety of a low-molecular-weight heparin were compared with those of unfractionated sodium heparin (standard heparin) in 136 patients who had elective total hip replacement. The patients received subcutaneous injection of either 5000 international units of low-molecular-weight heparin once daily or 5000 international units of standard heparin three times a day. Treatment with low-molecular-weight heparin began twelve hours before the operation, and treatment with standard heparin began two hours preoperatively; both regimens were continued for ten days. Twelve days postoperatively, bilateral ascending phlebography was performed in 122 patients, sixty-three in the treatment group that received low-molecular-weight heparin and fifty-nine in the treatment group that received standard heparin. Pulmonary scintigraphy was performed in 127 patients. Deep-vein thrombosis was diagnosed in forty-four patients: nineteen (30 per cent) of the sixty-three who received low-molecular-weight heparin and twenty-five (42 per cent) of the fifty-nine who received standard heparin. All but four patients, two from each treatment group, were asymptomatic. The difference in the total rate of thrombosis in the two groups was not significant (p = 0.189). However, thrombosis occurred in the thigh in only six (10 per cent) of the patients who received low-molecular-weight heparin but in eighteen (31 per cent) of those who received standard heparin, a significant difference (p = 0.011). Pulmonary embolism was detected in twenty-seven patients: eight (12.3 per cent) of those who received low-molecular-weight heparin and nineteen (30.6 per cent) of those who received standard heparin. Only three patients had clinical signs of embolism. Pulmonary embolism was significantly more frequent in the group that received standard heparin (p = 0.016). Total loss of blood and the total amount of blood that was transfused were significantly reduced in the patients who received low-molecular-weight heparin compared with those who received standard heparin. Prophylaxis was not discontinued because of hemorrhage in any patient. The efficacy of low-molecular-weight heparin was superior to that of standard heparin in the prevention of femoral thrombosis and pulmonary embolism, although the over-all incidence of deep-vein thrombosis was not statistically different.(ABSTRACT TRUNCATED AT 400 WORDS)

This review encompasses a description of the main pathophysiological events leading to disseminated intravascular coagulation (DIC). Emphasis has been put on microcirculatory disturbances and endothelial dysfunction. The normal hemostatic functions of the vascular endothelium are described. The close connection between endothelium and superimposed immuno-modulators is stressed as is the interrelation between the proteolytic cascade systems in the blood. The importance of differentiating local and systemic events is discussed. Organ dysfunction in multiple organ failure (MOF) is exemplified by pulmonary insufficiency in the adult respiratory distress syndrome (ARDS). Essential laboratory tests of DIC are described as are the cornerstones of treatment.

This article describes the formation of oxygen radicals and their biological effects, especially in relation to lung injury. Various recent experimental data are reviewed. The relationships between hydrostatic effects and permeability effects in producing injury and edema are stressed. Means of prevention and problems related to extrapolation to clinical situations are focused.

Objective: To examine the association between the serum lipoprotein (a) concentration and subsequent coronary heart disease., Design: Prospective case-control study based on a six year follow up of a general population sample of men aged 50 at baseline in 1983-4. Serum samples were frozen at the time of the baseline examination and kept at -70 degrees C for six years, after which the lipoprotein (a) concentrations in the samples were measured in cases and controls., Setting: City of Gothenburg, Sweden., Subjects: 26 Men, from a general population sample of 776 men, who had sustained a myocardial infarction or died of coronary heart disease during the six years and 109 randomly selected controls from the same sample who had remained free of myocardial infarction. In neither cases nor controls was there a history of myocardial infarction at baseline., Main Outcome Measures: Proportion of myocardial infarction or deaths from coronary heart disease, or both, in relation to the serum lipoprotein (a) concentration., Results: Men who suffered coronary heart disease had significantly higher serum lipoprotein (a) concentrations than controls (mean difference 105 mg/l; 95% confidence interval 18 to 192 mg/l). Men with the highest fifth of serum lipoprotein (a) concentrations (cut off point 365 mg/l) suffered a coronary heart disease rate which was more than twice that of men with the lowest four fifths of concentrations. Logistic regression analysis showed the serum lipoprotein (a) concentration to be significantly associated with coronary heart disease independently of other risk factors., Conclusion: The serum lipoprotein (a) concentration in middle aged men is an independent risk factor for subsequent myocardial infarction or death from coronary heart disease.

Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHR), is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor -1 (PAI-1) were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAI-1 levels correlated positively with glucose and insulin levels. PAI-1 was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI-1 levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity.

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.

In a retrospective analysis of 106 cases of endometrial carcinoma stages I-IV (FIGO), the prognostic value of DNA ploidy and nuclear morphometry of tumor cells was evaluated and compared with that of conventional clinical and histopathologic parameters. Paraffin-embedded tumor tissue from the original curettage specimens was used. A flow cytometric technique was employed to distinguish diploid from aneuploid tumors. It was not possible to estimate S-phase rates by this method. Eight different nucleus-related morphometric parameters were computed from representative tumor regions on the original slides. All histologic specimens were reviewed by on the pathologist and graded according to FIGO; nuclear grade was determined separately. Tumor stage, depth of myometrial infiltration, and nuclear grade were the most important prognostic factors with regard to tumor-related survival. DNA ploidy and nuclear morphometry did not add significant prognostic information that could be used to distinguish high-risk and low-risk populations with endometrial carcinomas. The simple nuclear grading system should be further evaluated in prospective studies and compared with DNA analysis and nuclear morphometry performed on fresh-frozen tissue.

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 the present communication venoscopy using a flexible choledochoscope is advocated after thrombectomy of the iliac veins. In 10 patients operated upon for occlusive thrombi in the pelvic veins, venoscopy was used to assess the status of the vein. The procedure was conveniently performed using a regular flexible choledochoscope. Venoscopy gave detailed information of the veins and lead to altered therapy in seven of the 10 patients. Venoscopy is recommended for intra-operative control during surgical thrombectomy and the use of a choledochoscope can simplify this procedure.

Vascular prostheses in humans do not endothelialize spontaneously. In the present study we explored the feasibility of seeding autologous endothelial cells into prostheses implanted in patients undergoing reconstruction of the infrarenal aorta. In 22 patients one limb of an aortic Dacron bifurcation prosthesis was seeded with autologous endothelial cells harvested from the distal portion of the saphenous vein. The other limb was sham-seeded with culture medium only. The effect of seeding was studied by use of indium 111 radiolabeled platelets and external gamma camera scanning at 1, 4, and 12 months after surgery. No complications ascribable to the seeding procedure were seen. During the first year after surgery a gradual decrease in platelet accumulation occurred over the whole vascular prosthesis. At all time points studied the seeded graft limbs exhibited significantly less deposition of radiolabeled platelets than did control limbs. The observed difference in platelet accumulation on autologous endothelial seeding-treated graft segments merits further investigation of this technique in humans.

Paraganglioma is a rare tumor in the upper respiratory tract. More than 30 paragangliomas have been reported arising in the larynx but only a few in the trachea. The organoid arrangements of the cell nests reproduce the classic 'Zellballen' of the normal gland. Neurosecretory granules can be seen at electron microscopy. Angiography may be a valuable diagnostic adjunct. Malignant degeneration may occur. The 44-year-old woman reported had a dumbbell-shaped tumor involving the subglottic larynx but with its largest portion outside the larynx and within the left lobe of the thyroid gland. The tumor may very well have arisen from the inferior laryngeal paraganglia. An important differential diagnosis is hemangiopericytoma, which was the preoperative diagnosis in this case. A laryngectomy including the left lobe of the thyroid gland was performed and there is no sign of local recurrence or metastases 7 years after operation.

Tissue fibrinolysis in the stomach and intestine of the rat was studied with a histochemical technique. After perfusion of blood vessels to reduce the influence of circulating plasminogen activator and inhibitor fibrinlysis was localized mainly to submucosal arteries and to the serosa of the gastrointestinal tract. This is opposite to previous observations, in which tissue fibrinolysis in the gastrointestinal tract was suggested to be mainly localized to veins. A method for semiquantitative analysis of tissue fibrolysis in the rat stomach is described.

Intravenous injection of a tumour cell suspension in rats induced an early tendency to increased fibrinolysis followed by a temporarily, significantly decreased fibrinolytic activity in lung vessels. These reactions were similar to those previously found after a large trauma and might reflect the vascular reaction to thrombotic material trapped in the lung microcirculation.

Nuclear enlargement in hyperfunctioning thyroid lesions which has been found in earlier cytophotometric studies is also one of the criteria in the subjective histological estimation of thyroid function. Histopathological assessment is, however, often unreliable. In the present study stage scanning cytophotometric measurements in Feulgen-stained tissue sections were used to determine the nuclear changes encountered in non-toxic and toxic nodular goitre, and in toxic diffuse goitre. To ensure optimal selection of specimens for measurements autoradiography was used. Specimens of toxic diffuse goitre invariably had enlarged nuclei, but no difference was found between nodules in nontoxic and toxic nodular goitre. In fact, the same nuclear area was found in hot nodules, warm nodules and perinodular tissue in non-toxic nodular goitre, and in hot nodules in toxic nodular goitre. Thus there are lesions with clear-cut clinical, biochemical, and autoradiographic hyperfunction that do not have enlarged nuclei. Against this background it is possible that the nuclear enlargement present in toxic diffuse goitre reflects the disorder in itself and not the hyperfunctioning state. Hyperdiploid cell nuclei were found in all cases of toxic diffuse goitre and in a higher percentage than in the other lesions. It was not possible to distinguish nontoxic and toxic nodular goitre on this basis.

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.

Gastric mucosal lesions were induced in rats by pyloric ligature and intragastric instillation of hydrochloric acid. Within 4 h all rats developed focal mucosal lesions. Early regeneration was observed 72 h after release of the pyloric ligature and replacement of the hydrochloric acid by a phosphate buffer. A significantly increased gastric mucosal fibrinolytic activity was found 4 h after pylorus ligation. The submucosal vascular fibrinolysis remained unchanged. Following release of the pyloric ligature the increased mucosal fibrinolysis returned to normal values after 72 h. Intravenous administration of tranexamic acid significantly decreased the mucosal and vascular fibrinolytic activity without influencing the formation of induced gastric lesions. Increased mucosal fibrinolysis is probably not involved in the development of mucosal lesions.

Oxygen consumption was compared in confluent cultures of endothelial cells from human umbilical cord veins, rat pulmonary arteries, and bovine aortas. A microrespirometric method utilizing oxygenated hemoglobin as oxygen supply and indicator of respiration was used. Respiratory rate was equal in human and murine cells (2.0 X 10(-6) and 2.2 X 10(-6) microliters O2/cell/hour respectively), compared on a cell-to-cell basis, while respiratory rate of the bovine endothelium was significantly lower (0.4 X 10(-6) microliters O2/cell/hour) (P less than .001).

Gastric ulcerations were induced in rats by pyloric ligature and instillation of 1.0 N HCl. After four hours all rats had developed ulcerations. Increased release of plasminogen activators from the mucosa during these conditions has previously been demonstrated. In the present study we investigated the role of fibrinolysis inhibition versus H2-receptor blockade on the gastric bleeding. Tranexamic acid - a synthetic inhibitor of the fibrinolytic system - was found to significantly (p less than 0.01) reduce blood loss into the gastric juice by 30% measured by 51Cr labelled red blood cells; cimetidine did not reduce the gastric haemorrhage under the experimental conditions used. Both treatment regimes significantly (p less than 0.02) reduced the secretion of gastric juice. These results indicate a contribution of the fibrinolytic system in gastric bleeding from experimentally induced gastric ulcerations.

The effects on the fibrinolytic system after a single s.c. bolus injection (at 9 a.m.) of either 5000 IU conventional heparin or 5000 anti-Xa U of a fractionated low molecular weight heparin (Fragmin, KabiVitrum, Sweden) were investigated in 9 healthy volunteers. The effects were compared to those of an injection of normal saline in 6 volunteers. Samples for biochemical analyses were taken regularily during 6 hours after drug or placebo administration. In the coagulation system the following parameters were measured: Activated partial thromboplastin time (APTT), anti-Xa activity, thrombin time and fibrinogen. The fibrinolytic system was monitored by analysing: plasminogen, alpha 2-antiplasmin, fibrin(ogen) degradation products (FDP), euglobulin clot lysis time (ECLT), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI) activity. Injection of the 2 drugs was followed by elevations in APTT and anti-Xa activity, and were more pronounced for Fragmin than heparin. The fibrinolytic system exhibited a diurnal variation with decreasing PAI activity and increasing t-PA activity during the day. Volunteers receiving normal saline (placebo) showed a similar pattern. The results were unrelated to heparin. It is concluded from this study that neither heparin nor Fragmin had any significant effect on the fibrinolytic parameters when measured after a single s.c. bolus injection since the observed variations were within the diurnal range.

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.

The cascade systems - the coagulation, fibrinolytic, kallikrein-kinin and complement systems - are all activated after trauma. These systems are involved in the post-traumatic pulmonary reaction. The complexity with which all the systems are intimately related is stressed. The specific role of the different systems in the development of post-traumatic pulmonary insufficiency remains to be evaluated.

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.

A new incision for retroperitoneal approach to the abdominal aorta is described. The incision extends from alongside the rectus abdominis muscle across the costal arch over the 7-8th intercostal space. In the upper part only the skin and muscles are divided, allowing wide opening of the incision. The approach is muscle-sparing, since fibers of the transverse abdominal muscle are incised only in the upper part. It permits a good approach even for high aortic reconstruction.

Tissue fibrinolysis in the rat stomach and transverse colon was studied after X-ray irradiation of the abdomen. Tissue biopsies were examined on unheated fibrin plates and with a histochemical technique modified from Todd. A significantly increased fibrinolytic activity was found in the mucosa of the stomach and colon 3 days after irradiation, while fibrinolysis localized to submucosal vessels was unchanged. Mucosal fibrinolysis in the stomach was significantly inhibited by intragastric administration of tranexamic acid.

In a randomized prospective trial, the efficacy of low molecular weight heparin (LMWH) (Fragmin) and dextran 70 (Macrodex) in preventing deep vein thrombosis (DVT) in the legs was evaluated in 98 consecutive patients undergoing elective total hip replacement. The patients were randomly allocated to receive either 2500 anti-factor Xa units LMWH twice daily for 7 days, with the first dose given 2 h before surgery; or 500 ml dextran 70 twice during the day of operation, followed by a single infusion of 500 ml on the first and again on the third postoperative day. DVT was assessed by 125I-fibrinogen test for 2 weeks postoperatively, a positive test being followed by phlebography. DVT developed in 22 (45 per cent) of 49 patients receiving dextran 70 and in 10 (20 per cent) of 49 patients in the LMWH group (P less than 0.01). LMWH was thus statistically significantly better than dextran 70 in preventing DVT in the legs. It was not firmly established whether this benefit was also valid in the high ileofemoral region. Two patients with non-fatal pulmonary embolism were found in each group. Per- and postoperative blood loss and blood transfusion requirements were significantly lower in the LMWH group.

The technique for transposition of infrarenal segments from the abdominal aorta and the caval vein, respectively, was described and morfological changes characterized. The vessel walls in the transposed caval segments became "arterialized" 1 month after the operation due to increased connective tissue in the media. Fibrin depositions were found on the intimal layer. The transposed aortic segments had no morfological changes. The described model was found to be a simple and valuable method for vascular research in small animals.

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.