Analgesic effect of intravenous dexamethasone after volar plate surgery for distal radius fracture with brachial plexus block anaesthesia: a prospective, double-blind randomised clinical trial.

Rebound pain after brachial plexus block resolution and development of long-lasting pain are problems associated with volar plate fixation for distal radius fractures. The aim of this double-blind study was to evaluate the effect of a single prophylactic intravenous dose of dexamethasone in this setting. The primary endpoint was highest pain score during the first 24 hours after surgery. We included 51 adults of ASA physical status 1-2 due to undergo planned acute fixation of the radius. All received premedication with oral paracetamol and etoricoxib, and a pre-operative brachial plexus block with ropivacaine. Patients were randomly allocated into two groups: a dexamethasone group receiving 16 mg dexamethasone intravenously at start of surgery and a control group receiving 4 ml saline. After surgery, all patients received fixed doses of paracetamol, etoricoxib and oxycodone, with further oxycodone added as needed in the first 48 hours. Pain, analgesic consumption and daily function were registered at predefined times up to 1 year after surgery. Median (IQR [range]) worst pain score in the first 24 hours, as assessed by verbal numeric rating scale (0-10), was 4 (2-6 [0-7]) in the dexamethasone group compared with 8 (5-8 [2-10]) in the placebo group (p < 0.001). Average pain score, 2 (1-4 [0-5]) vs. 5 (3-6 [0-8]), p = 0.001 and rescue oxycodone consumption, 5 (0-10 [0-35]) mg vs. 10 (5-15 [0-50]) mg, p = 0.037), respectively, were both significantly lower in the dexamethasone group compared with control from 8 to 24 hours. Brachial plexus block duration was 69% longer in the dexamethasone group, 21.5 (19.1-23.4 [12.9-24.1]) hours vs. 12.7 (11.9-15.3 [7.4-26.6]) hours, p < 0.001. Two patients (9%) in the dexamethasone group compared with 12 (50%) in the placebo group experienced worst pain scores of 8-10 during the first 36 hours (p = 0.002). At 3 and 7 days postoperatively, there were no significant differences between groups for pain scores or opioid consumption. At 6 months, 27 patients (57%) reported pain at the site of surgery, with significantly higher average pain score (p = 0.024) in the placebo group. At 1 year, two patients in the dexamethasone group reported pain compared with 10 in the placebo group (p = 0.015), and worst pain score was significantly higher in the placebo group (p = 0.018). We conclude that intravenous dexamethasone improves early postoperative analgesia and may also improve clinical outcomes after 6 and 12 months.

Microcirculation and haemodynamics after infraclavicular brachial plexus block using adrenaline as an adjuvant to lidocaine: a randomised, double-blind, crossover study in healthy volunteers.

We evaluated the effect of adrenaline on human skin microcirculation (nutritive and sub-papillary) and systemic cardiovascular variables after it was added to lidocaine in infraclavicular brachial plexus blocks. Twelve healthy, non-smoking male volunteers were included, each attending two study sessions 2 weeks apart, and they were studied using a crossover design. In both sessions, they received an ultrasound-guided infraclavicular brachial plexus block in the non-dominant arm with 0.4 ml.kg-1 lidocaine, 15 mg.ml-1 with or without adrenaline 5 µg.ml-1 . Microcirculation was assessed by laser Doppler fluxmetry (sub-papillary blood flow), capillary video microscopy (nutritive blood flow) and continuous temperature measurements. Heart rate and arterial pressure were recorded continuously and non-invasively. Median (IQR [range]) sub-papillary blood flow increased substantially 30 min after the brachial plexus block, from 8.5 (4.4-13.5 [2.9-28.2]) to 162.7 (111.0-197.8 [9.5-206.7]) arbitrary units with adrenaline (p = 0.017), and from 6.9 (5.3-28.5 [1.8-42.1] to 133.7 (16.5-216.7 [1.0-445.0] arbitrary units without adrenaline (p = 0.036). Nutritive blood flow (functional capillary density, capillaries.mm-2 , measured at the dorsal side of the hand) decreased in the blocked extremity when adrenaline was used as adjuvant, from median (IQR [range]) 45 (36-52 [26-59]) to 38 (29-41 [26-42]), p = 0.028, whereas no significant change occurred without adrenaline. Median finger skin temperature (°C) increased by 44% (data pooled) with no significant differences between the groups. No significant changes were found in the systemic cardiovascular variables with or without adrenaline. We conclude that lidocaine infraclavicular brachial plexus blocks caused an increase in skin sub-papillary blood flow. The addition of adrenaline produced stronger and longer lasting blocks, but decreased the nutritive blood flow.

Pre-operative brachial plexus block compared with an identical block performed at the end of surgery: a prospective, double-blind, randomised clinical trial.

We evaluated whether pre-emptive analgesia with a pre-operative ultrasound-guided infraclavicular brachial plexus block resulted in better postoperative analgesia than an identical block performed postoperatively. Fifty-two patients undergoing fixation of a fractured radius were included. All patients received general anaesthesia with remifentanil and propofol. Patients were randomly allocated into two groups: a pre-operative block or a postoperative block with 0.5 ml.kg-1 ropivacaine 0.75%. After surgery, all patients received regular paracetamol plus opioids for breakthrough pain. Mean (SD) time to first rescue analgesic after emergence from general anaesthesia was 544 (217) min in the pre-operative block group compared with 343 (316) min in the postoperative block group (p = 0.015). Postoperative pain scores were higher and more patients required rescue analgesia during the first 4 h after surgery in the postoperative block group. There were no significant differences in plasma stress mediators between the groups. Analgesic consumption was lower at day seven in the pre-operative block group. Pain was described as very strong at block resolution in 27 (63%) patients and 26 (76%) had episodes of mild pain after 6 months. We conclude that a pre-operative ultrasound-guided infraclavicular brachial plexus block provides longer and better analgesia in the acute postoperative period compared with an identical postoperative block in patients undergoing surgery for fractured radius.

Hip fracture, mortality risk, and cause of death over two decades.

UNLABELLED: Men and women with hip fracture have higher short-term mortality. This study investigated mortality risk over two decades post-fracture; excess mortality remained high in women up to 10 years and in men up to 20 years. Cardiovascular disease (CVD) and pneumonia were leading causes of death with a long-term doubling of risk. INTRODUCTION: Hip fractures are associated with increased mortality, particularly short term. In this study with a two-decade follow-up, we examined mortality and cause of death compared to the background population. METHODS: We followed 1013 hip fracture patients and 2026 matched community controls for 22 years. Mortality, excess mortality, and cause of death were analyzed and stratified for age and sex. Hazard ratio (HR) was estimated by Cox regression. A competing risk model was fitted to estimate HR for common causes of death (CVD, cancer, pneumonia) in the short and long term (>1 year). RESULTS: For both sexes and at all ages, mortality was higher in hip fracture patients across the observation period with men losing most life years (p < 0.001). Mortality risk was higher for up to 15 years (women (risk ratio (RR) 1.9 [95 % confidence interval (CI) 1.7-2.1]); men (RR 2.8 [2.2-3.5])) and until end of follow-up ((RR 1.8 [1.6-2.0]); (RR 2.7 [2.1-3.3])). Excess mortality by time intervals, censored for the first year, was evident in women (<80 years, up to 10 years; >80 years, for 5 years) and in men <80 years throughout. CVD and pneumonia were predominant causes of death in men and women with an associated higher risk in all age groups. Pneumonia caused excess mortality in men over the entire observation period. CONCLUSION: In a remaining lifetime perspective, all-cause and excess mortality after hip fracture was higher even over two decades of follow-up. CVD and pneumonia reduce life expectancy for the remaining lifetime and highlights the need to further improve post-fracture management.

Risk factors for cardiovascular disease and future osteoarthritis-related arthroplasty: a population-based cohort study in men and women from Malmö, Sweden.

OBJECTIVE: To investigate the hypothesis that cardiovascular risk factors increase the likelihood of future osteoarthritis (OA)-related arthroplasty in adult men and women. METHODS: Baseline cohort data on cardiovascular risk factors [age, socio-economic class, family history, obesity, smoking, glucose, cholesterol, blood pressure, and early cardiovascular disease (CVD) history] were linked to clinical registers of OA-related arthroplasty data. The study included 8749 women and 14 821 men with up to a 30-year follow-up. RESULTS: In women, higher cardiovascular risk groups were more likely to have an OA outcome compared to the lowest risk quartile group (trend p < 0.001). The estimates were as follows: second quartile risk: rate ratio (RR) 2.15, 95% confidence interval (CI) 1.6-2.9, third quartile risk: 3.32 (2.5-4.5); and highest risk quartile: 3.47 (2.6-4.7). In men, higher cardiovascular risk groups were also more likely to have an OA outcome compared to the lowest risk quartile group (trend p = 0.001). The estimates were as follows: second quartile risk: RR 1.44, 95% CI 1.1-1.9; third quartile risk: 1.38 (1.1-1.8); and highest risk quartile: 1.67 (1.3-2.2). CONCLUSIONS: Our large cohort study with up to a 30-year follow-up period provides evidence to support the hypothesis of shared risk factors in CVD and OA, and the findings suggest an alternative aetiological process in the pathogenesis of OA.

The association between hyperglycemia and fracture risk in middle age. A prospective, population-based study of 22,444 men and 10,902 women.

AIMS: Type 1 diabetes mellitus is associated with increased fracture risk, whereas the risk associated with type 2 diabetes is less obvious. Elevated fasting blood glucose and high 2-h glucose during an oral glucose tolerance test indicate impaired glucose tolerance or diabetes. The associations among fasting blood glucose, 2-h glucose, and the risk of fracture were investigated. METHODS: The Malmö Preventive Project consists of 22,444 men (44+/-6.6 yr) and 10,902 women (50+/-7.4 yr), with a follow-up of 19 yr (+/-3.9) and 15 yr (+/-4.5) for incident fractures. Baseline assessment included multiple examinations and lifestyle information. A logistic regression model was used. Adjustments were made for age, body mass index (BMI), and smoking. RESULTS: Low-energy fractures were recorded in 1246 men and 1236 women. A 2-h glucose measurement between 4.3 and 6.2 mmol/liter in men (second and third quartile), and above 6.5 mmol/liter in women (third and fourth quartile), adjusted for age, BMI, and smoking, was significantly associated with a decreased risk of multiple fractures, in men [odds ratios (ORs) 0.57-0.71] and women (ORs 0.38-0.66). In women, a 2-h glucose measurement above 7.5 mmol/liter was associated with a decreased risk of osteoporotic fractures (OR 0.57, 95% confidence interval 0.44-0.74). CONCLUSIONS: In middle-aged men and women, elevated 2-h glucose levels were associated with decreased risks of multiple and osteoporotic fractures, independent of age, BMI, and smoking. A high 2-h glucose level is characterized by peripheral insulin resistance with a high insulin level. Our findings indirectly suggest a positive effect on bone from hyperglycemia.

Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women.

The incidence of fragility fractures begins to increase in middle age. We investigated prospectively risk factors for low-energy fractures in men and women, and specifically for forearm, proximal humerus, vertebral, and ankle fractures. The population-based Malmö Preventive Project consists of 22,444 men and 10,902 women, mean age 44 and 50 years, respectively, at inclusion. Baseline assessment included multiple examinations and lifestyle information. Mean follow-up was 19 and 15 years for men and women, respectively, regarding incident fractures. Fractures were ascertained from radiographic files. At least one low-energy fracture occurred in 1,262 men and 1,257 women. In men, the risk factors most strongly associated with low-energy fractures were diabetes [relative risk (RR) 2.38, confidence interval (CI) 95% 1.65-3.42] and hospitalization for mental health problems (RR 1.92, CI 95% 1.47-2.51). Factors associated with mental health and lifestyle significantly increased the fracture risk in most of the specific fracture groups: hospitalizations for mental health problems (RR 2.28-3.38), poor appetite (RR 3.05-3.43), sleep disturbances (RR 1.72-2.95), poor self-rated health (RR 1.80-1.83), and smoking (RR 1.70-2.72). In women, the risk factors most strongly associated with low-energy fractures were diabetes (RR 1.87, CI 95% 1.26-2.79) and previous fracture (RR 2.00, CI 95% 1.56-2.58). High body mass index (BMI) significantly increased the risk of proximal humerus and ankle fractures (RR 1.21-1.33) while, by contrast, lowering the risk of forearm fractures (RR 0.88, CI 95% 0.81-0.96). Risk factors for fracture in middle-aged men and women are similar but with gender differences for forearm, vertebral, proximal humerus, and hip fracture whereas risk factors for ankle fractures differ to a certain extent. The risk-factor pattern indicates a generally impaired health status, with mental health problems as a major contributor to fracture risk, particularly in men.

Activation of coagulation and fibrinolytic systems in patients with CLI is not normalized after surgical revascularisation.

OBJECTIVE: To study the activation of coagulation and fibrinolysis before, during and after surgical revascularisation in patients with critical limb ischemia (CLI). DESIGN: Prospective clinical study. MATERIALS AND METHODS: Forty patients with CLI underwent femoro-popliteal or femoro-distal reconstruction and were compared to a control-group. Measurements of prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) assessed activation of coagulation. Fibrinolysis was determined by tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and fibrin degradation product (D-dimer). The inflammatory mediators: Interleukin 2 receptor (IL-2-rec), Interleukin 6 (IL-6), Interleukin 10 (IL-10) and Monocyte chemoattractant protein 1 (MCP-1) was also analysed. RESULTS: Patients (in 35 of the 40 reconstruction was possible) were operated upon using either vein (n=23) or ePTFE (n=12) grafts. Patients with CLI had a preoperative prothrombotic state as indicated by high TAT-levels and also ongoing fibrinolysis with high levels of t-PA and D-dimer. After reperfusion an ongoing prothrombotic state for the first week was demonstrated. A significant as well as defective fibrinolysis was also seen with increased levels of tPA and D-dimer unopposed by PAI-1 after one week and also after 30 days. Increased levels of inflammatory mediators IL-6, IL-10 and MCP-1 was observed after reperfusion and normalised after 30 days. CONCLUSION: This study demonstrates significant disturbances of both the coagulation and fibrinolytic systems before, during and after revascularisation for CLI. This was accompanied by release of inflammatory mediators. A prothrombotic state and increased fibrinolysis were evident also 30 days after successful revascularisation.

Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer.

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.

Occurrence of neurotrophin receptors and transmitters in the developing Xenopus gut.

The ontogeny of gut innervation in the anuran amphibian Xenopus laevis was studied using immunohistochemistry on sections of whole larvae from NF stages 38-52. Immunoreactivity to acetylated tubulin confirmed the presence of nerve fibres as early as stages 38-39. Actin immunoreactivity was found at stage 41, indicating the presence of smooth muscle cells. Trk-like neurotrophin receptors were occasionally found in nerve fibres as soon as stages 38-39. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivities coexisted in nerves innervating the gut wall from stages 40-41, and nitric oxide synthase (NOS) from stage 42. Substance P/neurokinin A (SP/NKA) occurred at stage 42. In all these cases, the first fibres were observed in the oesophagus. Calcitonin gene-related peptide (CGRP) was first observed in nerves at stage 48. In general, VIP/PACAP and NOS innervation was denser than the tachykinin innervation. In conclusion, the development of nerve fibres in the Xenopus gut is probably dependent on neurotrophins that may act via Trk-like receptors and occur before the gut wall is fully organised morphologically. Feeding in Xenopus larvae starts at NF stage 45. The study demonstrates that several of the transmitters investigated are expressed in the gut innervation (and in endocrine cells) prior to this stage.

Technetium-99m labelling of glycosylated somatostatin-14.

This study presents a technetium-99m labelling method based on organometallic chemistry. It describes the simple mixing of a 99mTc(I)-carbonyl compound [99mTc(OH2)3(CO)3]+ with a histidine-tagged somatostatin-dextran (SMS-Dx-His) conjugate. Somatostatin and histidine was coupled to periodate activated dextran. The linkage was stabilised by reductive amination. The conjugate was then radiolabelled with 99mTc by using the 99mTc(CO)3 core. The labelling efficiency was 65-80% and the radiochemical purity > 95%. In the in vitro cysteine challenge, the result showed that 25% of the radiolabel was released after 1 h incubation at 37 degrees C (cysteine-conjugate at 1000:1 molar ratio). The radiolabelled SMS-Dx-His showed similar HPLC profile as the unlabelled conjugate. This labelling method, employing non reducing conditions, is useful for the labelling of peptides containing disulphide bonds. It should be possible to be used also for labelling with rhenium-188 for therapeutic applications.

Biodistribution, blood half-life, and receptor binding of a somatostatin-dextran conjugate.

Derivatives of somatostatin (sms) are attracting increasing interest as part of the treatment of several cancer diseases expressing sms receptors (srs). Radiolabeled sms analogs can additionally be used for systemic radiotherapy and for diagnostic investigations. Glycosylated sms-14 (sms-dextran70) was characterized regarding in vitro srs binding, biodistribution, and blood half-life in mice. Rat brain cortex membranes (expressing srs 2) were used for the srs binding study. Tyr3-Octreotide was used as positive control. The binding data were analyzed by competition curve analysis. In the biodistribution study, the Bolton-Hunter reagent was used for the radioiodination of sms-dextran70. Organs and blood were collected at different time-points and the percentage of the injected dose per gram of tissue (%ID/g) was calculated. The conjugate was administered subcutaneously (sc). The sms-dextran70 showed high srs binding affinity (i.e., in the same nanomolar range as the reference ligand Tyr3-octreotide (IC50 approximately 2.5 nM). The blood half-life was approx 27 h after reaching maximum blood concentration 24 h postinjection. Because of the molecular weight of the conjugate (i.e., approx 75,000) being above the kidney threshold for dextran (i.e., 50,000), the digestion and excretion is assumed to be mainly through the hepatobiliary system. Increased uptake was seen in the adrenals, which are receptor-positive organs. Some accumulation was seen in the stomach, indicating certain deiodination of the conjugate label. The sms-dextran70 showed promising properties and its clinical relevance is currently being evaluated in clinical phase I-II studies.

Intravesical administration of EGF- dextran conjugates in patients with superficial bladder cancer.

OBJECTIVES: Overexpression of the epidermal growth factor receptor (EGFR) has been reported in bladder cancer and is a potential target for therapy with radionuclides. In this study, we investigated the binding of EGF-dextran-(99m)Tc to the EGFR. The aim of this study was to determine if intravesically administered EGF-dextran conjungate selectively accumulated in the tumor tissue and to correlate the uptake to tumor characteristics. METHODS: Eight patients received the conjugate intravesically for about 30 min followed by bladder irrigation and then transurethral resection. Radioactivity of the biopsy specimens from normal urothelium and tumor areas was measured in a gamma counter. RESULTS: Five patients received EGF-dextran-(99m)Tc, three received dextran-(99m)Tc and one received only (99m)Tc. The 5 patients who received the complete conjugate had a mean ratio of radioactivity between tumor and normal urothelium of 664:1 (range: 2.4-1,710). The dextran-(99m)Tc showed a slightly increased ratio and (99m)Tc did not bind at all. CONCLUSION: The results are encouraging and further studies are warranted to investigate if EGF-dextran could be effective as intravesical therapy, either conjugated with cystostatic drugs or labeled with suitable radionuclides.

Radiolabeling of dextran with rhenium-188.

This study describes a method for the radiolabeling of dextran with rhenium-188 (188Re). In nuclear oncology 188Re is very useful for therapeutic applications. Its nuclear characteristics allow radiotherapy and in situ monitoring of tumor uptake as well as dosimetry calculations. Consequently new compounds with this radiolabel are of general interest. Dextran was oxidized with sodium periodate yielding reactive aldehyde groups and subsequently reacted with cysteine. The linkage was stabilized by reducing the Schiff bases with sodium cyanoborohydride. The conjugate was then radiolabeled with 188Re by using 188Re-gluconate as the transchelator, labeling the free thiols. Synthesis and radiolabeling were done in the absence of oxygen. The labeling efficiency was 60-70% and the radiochemical purity > 95%. The in vitro stability study, using "cysteine challenge" demonstrated that 50% of the radiolabel was transcomplexed to the 100 mM cysteine solution (after 1 h incubation at 37 degrees C). However, at physiologic conditions and presence of an antioxidant good stability was achieved. The 188Re labeled dextran presented in this study provides a template with therapeutic and diagnostic potential in nuclear oncology, either alone for local treatment or as a backbone in a tumor specific conjugate for systemic treatment.

Human milk fat globule antigen 1 (HMFG1) expression in prostatic carcinoma and immunotargeting with a radiolabelled monoclonal anti-HMFG1 antibody.

BACKGROUND: Prostatic cancer is the leading cause of death in Swedish men. Approximately 50% have disseminated disease at diagnosis. Radiolabelled antibodies could possibly be a treatment modality for disseminated prostatic cancer, so that in this study the expression of the human milk fat globulin 1 (HMFG1) antigen in prostate cancer was examined. MATERIALS AND METHODS: An immunohistochemistry technique with a murine monoclonal antibody was used, as well as the human prostate cancer cell line DU-145, which expresses this cell surface antigen. TUR specimens from patients with prostate cancer were also examined. RESULTS: Eighteen out of 22 (82%) patients exhibited an HMFG1-positive tumour. An inhomogenity in the immunostaining could occasionally be seen, with smaller apparently negative areas. The immunolocalisation properties of the antibody were investigated using a radiolabelled antibody injection into nude mice bearing heterotransplants of the DU-145 cell line. The highest accumulation of the antibody was seen in the tumour tissue and the liver. CONCLUSION: The results obtained form a basis for further investigations with the goal of using the antibodies for staging and therapy for prostate cancer.

Gadolinium-enhanced magnetic resonance angiography, digital subtraction angiography and duplex of the iliac arteries compared with intra-arterial pressure gradient measurements.

PURPOSE: to compare gadolinium-enhanced magnetic resonance angiography (Gd-MRA), digital subtraction angiography (DSA) and duplex of the iliac arteries with intra-arterial pressure gradient measurement as the reference method. MATERIALS AND METHODS: Gd-MRA, DSA and duplex examinations of the iliac arteries were performed in 30 patients (60 arteries) with lower-limb arterial occlusive disease. In 29 arteries, pressure measurements were made (n=25) or the artery was found to be occluded on catheterisation (n=4). An aortofemoral peak systolic pressure gradient of 20 mmHg or more was regarded as haemodynamically significant. Stenoses with a diameter reduction of 50% or more on MRA or DSA, or an increase in peak systolic velocity greater than 150% (duplex) were considered significant. MRA examinations were evaluated by means of maximum intensity projections (MRA-MIP) and using source images and curved multiplanar reconstruction (MRA-MPR). RESULTS: the sensitivity (specificity) for a significant iliac artery stenosis were 81% (75%) for MRA-MIP, 76% (75%) for MRA-MPR, 86% (88%) for DSA, and 72% (88%) for duplex. CONCLUSION: with intra-arterial pressure measurements as the reference method, similar results were achieved with Gd-MRA, DSA and duplex concerning the detection of haemodynamically significant iliac artery stenoses. The use of source images and multiplanar reconstructions resulted in higher accuracy for the detection of occlusions.

Hemorheologic variables in critical limb ischemia before and after infrainguinal reconstruction.

PURPOSE: Plasma and whole blood viscosity are elevated in patients with intermittent claudication. The objectives of this study were to investigate whether critical limb ischemia influences hemorheologic variables and whether the rheologic variables in blood from the affected limb differ from the general circulation. We also intended to study whether successful infrainguinal reconstruction improved hemorheologic variables. METHODS: Ten consecutive patients with critical limb ischemia (CLI) underwent arterial reconstruction, one patient with profundaplasty and nine patients with bypass procedures. Venous blood was sampled from the antecubital vein (arm) and the femoral vein (leg) of the affected limb 1 day before and 1 month after surgery. Ten control subjects (matched according to age, sex, diabetic status, and renal insufficiency) were also sampled. Whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency, and erythrocyte fluidity (the latter variable describing the deformability of the erythrocytes) were measured by means of rotational viscometry. Erythrocyte volume fraction was also determined. Fibrinogen was measured in the patients with CLI. RESULTS: Erythrocyte fluidity, blood viscosity, and erythrocyte volume fraction were lower in patients with CLI than in control subjects (P <.01, P <.01, and P <.05, respectively). No major differences between cubital and femoral vein blood were seen before or after the operation in patients with CLI or in control subjects. Successful revascularization did not influence the hemorheologic variables, except for a decrease in blood viscosity in femoral vein blood (P <.05). CONCLUSION: Hemorheologic properties was impaired in patients with CLI. Because no differences were seen between the systemic and local circulation and because no major improvement occurred 1 month after arterial reconstruction, other mechanisms besides local tissue ischemia may play a role.

Ion exchange tumor targeting: a new approach.

Connective tissues are distinguished by the types, concentrations, and organizations of material in the extracellular matrix. Many physiological functions are determined largely by the nature and organization of the extracellular components. The components are characterized by their content and distribution of charged, mostly anionic groups. The distinct roles played by the charges are sometimes modeled by analogy to the transport theory of ion exchange resins. The intent of this study was to investigate whether the properties of the tumor matrix could be used for selective, charge-dependent accumulation of charge-modified dextran. Ten patients with diagnosed superficial urinary bladder carcinoma were included in the study. They received intravesical instillations of technetium-99m-labeled charge-modified dextran derivatives (approximately 0.1-1 mg; approximately 50 MBq in saline; 30-min incubation). After treatment and resection, samples were taken from normal and diseased tissue. The result clearly demonstrated a charge-dependent difference in the quotient of radioactive uptake in tumor tissue: normal tissue. Instillations of cationic dextran yielded a high quotient, up to 3000. Normal tissue had background activity. Anionic dextran yielded a low quotient, 1.8-2, with increased background (i.e. uptake in normal tissue). Neutral dextran gave a quotient of up to 90. No radioactivity could be detected in blood. The tumors in this study apparently displayed cation-exchanging properties. We will continue this investigation and determine whether this is a general property of bladder carcinomas and whether other carcinomas display ion exchange properties. If this is the case, the finding could have important implications for the local treatment of several cancers.

Coagulation and fibrinolysis after open infrarenal abdominal aortic aneurysm repair in a long-term perspective.

In patients with abdominal aortic aneurysms (AAA) the coagulation and fibrinolytic systems have been found to be activated preoperatively. Does the increased activity of the coagulation and fibrinolytic systems persist after AAA surgery in a long-term perspective? Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), tissue plasminogen activator (tPA), human plasminogen activator inhibitor type 1, and human cross-linked fibrin degradation product (D-dimer) were analysed in 18 patients after open AAA surgery (postop-AAA). The median time between surgery and blood sampling was 19 months (range, 5-37 months). Comparisons were made with both preoperative values of 23 patients with AAA (preop-AAA) as well as 20 age-matched healthy controls (AMC). F1+2, TAT, and D-dimer in preop-AAA were significantly higher compared to AMC (p<0.001). In post-op AAA patients these parameters were significantly lower compared to preop-AAA (p<0.05 for F1+2 and TAT, p<0.001 for D-dimer). However, TAT and D-dimer levels were still higher in postop-AAA than in AMC (p<0.01 for both). The activity of the coagulation and fibrinolytic systems seems to decrease after AAA surgery. However, the activity is still higher than in healthy AMC. A possible explanation may be that the thrombogenicity is lower in a vascular graft than in an aneurysmal sac but still higher than in a nonaneurysmal aorta.

Ischaemia and reperfusion during open abdominal aortic aneurysm surgery induce extensive thrombin generation and activity.

OBJECTIVES: does open surgery for abdominal aortic aneurysm (AAA) influence coagulation? METHODS: in 23 patients operated on for AAA, cubital blood was sampled pre-, intra- and postoperatively. Femoral blood was also sampled intraoperatively. RESULTS: preoperatively, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and soluble fibrin (SF) were elevated in AAA patients. During aortic clamping all parameters increased significantly in cubital blood (p<0.01) as well as in femoral blood (p<0.001) and after aortic declamping F1+2 and TAT increased further. F1+2, TAT and SF were significantly higher in femoral than cubital blood. Postoperatively F1+2 and TAT returned to preoperative values, while SF still had a significantly higher level than preoperatively (p<0.001). Blood loss showed co-variation with F1+2 increase in femoral blood after aortic declamping (p<0.05). CONCLUSIONS: these data indicate that the coagulation system was strongly activated by the occurrence of an AAA. During AAA surgery a further extensive activation was seen. The activity was still high, but on decline, one week postoperatively. Ischaemia and reperfusion of the lower part of the body were the major stimuli for thrombin generation and activity.