Prostanoids for intermittent claudication.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity in the general population. While numerous studies have established the efficacy of prostanoids in PAOD stages III and IV the question of the role of prostanoids as an alternative or additive treatment in patients suffering from claudicatio intermittens (PAOD II) has not yet been clearly answered. OBJECTIVES: The aim of this review was to evaluate effects of prostanoids in patients with intermittent claudication. SEARCH STRATEGY: Computerised searches of the Cochrane Peripheral Vascular Diseases Specialised Register (last searched April 2003), The Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1, 2003), MEDLINE and EMBASE were undertaken. In addition relevant journals were hand-searched. SELECTION CRITERIA: Randomized clinical trials describing the effects of prostanoids in the treatment of patients suffering from intermittent claudication have been considered for inclusion. DATA COLLECTION AND ANALYSIS: All reviewers assessed the quality of studies and extracted data unblinded. Statistical analysis including tests for heterogeneity and overall effect were performed by using MetaView of Review Manager 4.2. All numeric values are expressed as mean +/- Standard deviation (SD). MAIN RESULTS: Eighteen studies were included for analysis. A significant heterogeneity between the included studies was detected in most of the subgroup analysis. Five studies compared the effects of prostaglandin E1 (PGE1) versus placebo, and reported in their individual results significant increases in walking distances after the administration of PGE1. The attained increase in walking distances appears to be not merely a short-term effect because several studies reported that walking capacity remained increased even after termination of treatment. On the other hand, oral or intravenous prostacyclin did not increase the walking distances significantly. At least one adverse reaction was reported from 23.6% of the patients treated with prostacyclin (PGI2), and its analogues and from 13.7% of the patients treated with PGE1. REVIEWER'S CONCLUSIONS: Because of the heterogeneity between most of the included studies, we did not pool relevant parts of the data by meta-analysis. Based on the individual results of the published literature, patients with intermittent claudication seem to benefit from administration (intravenous or intra-arterial) of PGE1 by a significant improvement of their walking capacity. Further well-conducted randomized, double blinded trials, with a sufficient number of patients to provide statistical powerful information, should be performed to confirm the results of this review.

Influence of lipoprotein(a) on restenosis after femoropopliteal percutaneous transluminal angioplasty in Type 2 diabetic patients.

OBJECTIVE: The influence of vascular morphology and metabolic parameters including lipoprotein(a) (Lp(a)) on restenosis after peripheral angioplasty has been compared in Type 2 diabetes (DM) vs. non-diabetic patients (ND). RESEARCH DESIGN AND METHODS: The clinical course and risk profile of 132 (54 DM vs. 78 ND) patients with peripheral arterial occlusive disease (PAD) were observed prospectively following femoropopliteal angioplasty (PTA). Clinical examination, oscillometry, ankle brachial blood pressure index (ABI) and the toe systolic blood pressure index (TSPI) were used during follow-up. Duplex sonography and reangiography were also used to verify suspected restenosis or reocclusion. RESULTS: At the time of intervention patients with DM had a lower median Lp(a) of 9 vs. 15 mg/dl (P < 0.01) in patients without diabetes. Recurrence within 1 year after PTA occurred in 25 diabetic (= 46%, Lp(a) 12 mg/dl) and 30 non-diabetic (= 38%, Lp(a) 48 mg/dl) patients. DM patients with 1 year's patency had a median Lp(a) of 7 vs. 11 mg/dl in non-diabetic patients (P < 0.05). However, 12 months after angioplasty Lp(a) correlated negatively with the ABI (r = -0.44, P < 0.01) in diabetic and in non-diabetic patients (r = -0.20, P < 0.05). The probability of recurrence after PTA continuously increased with higher levels of Lp(a) in each subgroup of patients. CONCLUSIONS: Our data indicate that Lp(a) is generally lower in those with peripheral arterial occlusive disease and Type 2 diabetes than in non-diabetic individuals. The increased risk for restenosis with rising levels of Lp(a) is set at a lower Lp(a) in diabetes and may be more harmful for diabetic patients.

Prostanoids in the treatment of intermittent claudication--a meta-analysis.

BACKGROUND: Numerous studies have established the efficacy of prostanoids in PAD stages III and IV, but the role of prostanoids as an alternative or additive treatment in patients suffering from PAD II is less clear. To resolve this uncertainty we performed a meta-analysis of all randomised controlled studies analysing effects of prostanoids in patients suffering from intermittent claudication. METHODS: 96 studies have been screened by computerised searches of MEDLINE and EMBASE. Relevant studies were pooled in Cochrane's Review-manager 4.1. RESULTS: 19 studies were included for further analysis. Five studies could not be pooled for analysing walking distances, because standard deviations were not stated. Eight studies compared effects of any prostanoid i.v. vs. placebo. In total 557 patients (281/276) were included for analysis of painfree--walking distance (PFWD) and 519 patients (262/257) for analysis of maximum walking distance (MWD). Prostanoids compared to placebo significantly improved mean PFWD by 28% (7%-49%, P = 0.008) and mean MWD by 30% (11%-50%, P = 0.002). At least one adverse reaction was reported from 39.6% of the patients treated with prostacyclin and its analogues and from 13.7% of the patients treated with prostaglandin E1. CONCLUSION: Patients suffering from intermittent claudication benefit from administration of prostaglandin E1 by a significant improvement of their walking capacity.

The bridge graft: a new concept for infrapopliteal surgery.

BACKGROUND: The long-term results of ePTFE grafts are particularly poor in crural reconstructions. We report on a novel surgical technique, whereby both run-off and anastomotic mismatches are concomitantly addressed. PATIENTS AND METHODS: Short segments of vein grafts (5-15 cm in length) were used to bridge two crural artery segments. Subsequently, a femoro-distal ePTFE graft was anastomosed to the bridge graft. Venous valves were made incompetent to allow bi-directional flow. In a retrospective series of 45 patients with crural bridge grafts, 12 patients were in stage III and 33 in stage IV. In 18 patients the reconstruction was the first procedure and in the remaining 28 patients it was the first or second re-operation. RESULTS: The primary patency rate at 1, 2, 3 and 4 years was 53, 44, 35 and 26% respectively. The secondary patency rate was 67, 53, 49 and 39% respectively. The corresponding limb salvage rate was 70, 61, 56 and 45%. In a small subgroup of patients, in which the crural bridge was the first reconstructive procedure, the primary patency was 76 at 1 year and 64 at 4 years. CONCLUSION: convincing long-term crural bridge grafts should be considered in those patients who have more than one crural or pedal artery available for grafting and an insufficient length of saphenous vein.

Effects of transvenous regional guanethidine block in the treatment of critical finger ischemia.

The objective of this study was to determine the effects of transvenous regional guanethidine block in the treatment of patients with critical finger ischemia. Twenty-seven patients (17 collagen vascular disease, four thromboangiitis obliterans, three embolism, three atherothrombosis) presenting with ischemic rest pain and/or ulcerations of the fingers received a single block with 5 mg guanethidine injected in 60 mL into the clinically more affected hand under 30 minutes of arterial arrest. Marked hyperemia was induced in the treated upper limb, increases (p < 0.01) in finger blood flow, finger skin temperature, and laser Doppler flux were higher and longer lasting than in forearm blood flow, persisting for a whole month. Effects in patients with ischemic finger ulcers were less pronounced than in those without, yet statistically significant increases of all evaluated parameters were observed in these patients too. No effects were seen in the contralateral untreated upper limb or in systemic blood pressure. Subjective symptoms (reduction of rest pain, numbness, vasospastic attacks) were improved in 25/27 (92.6%) patients, ischemic rest pain disappeared in 20/27 (74.1%), and complete healing of finger tip ulcerations within 1 month was achieved in 10/12 (83.3%) affected patients. No side effects were observed. This described method combines good clinical efficacy with lack of undesirable side effects and can be repeated easily. Therefore, this technique is recommended for broader clinical use.

The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene.

A G20210A transition in the prothrombin gene is a common risk factor of venous thrombosis. The risk of recurrent venous thromboembolism in carriers of the 20210A allele is unknown and guidelines for secondary thromboprophylaxis in these patients are not available. In a prospective multicenter trial, 492 patients with a history of objectively documented venous thromboembolism were followed for a mean observation time of 24+/-16 months after discontinuation of oral anticoagulants. Forty-two patients (8.5%) were carriers of the 20210A allele. Three of the 42 patients with the G20210A mutation (7%) and 54 of 450 patients without the mutation (12%) experienced recurrent venous thrombosis. At 24 months, the probability of recurrence was 8% (95% CI 0-16.7) in patients with the mutation and was 12.2% (95% CI 8.8-15.6) in patients without the mutation. In conclusion, the risk of early recurrent venous thromboembolism is not higher in patients with the G20210A mutation than in those without the mutation. Therefore, long-term secondary thromboprophylaxis with oral anticoagulants in heterozygous carriers of the 20210A allele is not justified.

Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism.

Hyperhomocysteinemia is a risk factor of venous thromboembolism. The risk of recurrence in patients with hyperhomocysteinemia is unknown, and the optimal therapy for these patients after acute venous thromboembolism is uncertain. In a multicenter study, 264 patients with an objectively documented single episode of idiopathic venous thromboembolism were prospectively followed after discontinuation of oral anticoagulants. Patients were classified as hyperhomocysteinemic if their homocysteine levels exceeded the 95th percentile of the controls. The outcome events studied were objectively confirmed deep-vein thrombosis and/or pulmonary embolism. Homocysteine levels were elevated in 66 patients (25%) and normal in 198 patients (75%). Recurrent venous thromboembolism occurred in 12 of 66 patients with hyperhomocysteinemia (18.2%) and in 16 of 198 patients without hyperhomocysteinemia (8.1%). The cumulative probability of recurrence 24 months after discontinuation of oral anticoagulants was 19.2 percent (95 percent confidence interval 8.7-27) in patients with hyperhomocysteinemia and was 6.3 percent (95 percent confidence interval 2.4-10.1; p = 0.001) in those without hyperhomocysteinemia. The relative risk of recurrent thrombosis was higher in patients with hyperhomocysteinemia [RR 2.7 (1.3-5.8), p = 0.009]. Patients with hyperhomocysteinemia are at high risk of recurrent venous thromboembolism. The high prevalence of hyperhomocysteinemia in thrombosis patients together with the increased risk of recurrence warrants extended patient screening. The impact on the risk of recurrence of prolonged anticoagulation, supplementation of folate and vitamin B12, or both have to be investigated.

Color duplex sonography guided stent placement in a stenosis of the superficial femoral artery. A case report.

We report the first case of a successful stent placement under color coded ultrasound guidance alone in the superficial femoral artery of a 73-year-old woman suffering from intermittent calf claudication following restenosis after an uncomplicated angioplasty five months previously. Because of a hemodynamically residual stenosis after three attempts at dilatation, a percutaneous transluminal angioplasty and stent insertion were performed under the sole guidance of color coded ultrasound. The intervention was performed without complication and at the six-month follow-up examination, the patient was symptom-free and the stent was morphologically intact and hemodynamically functional. This case shows that successful stent placement under ultrasonic guidance alone, without fluoroscopic control is possible, provided that there is adequate sonographic visualization.

Clinical studies and thrombin generation in patients homozygous or heterozygous for the G20210A mutation in the prothrombin gene.

A genetic variation in the prothrombin gene, the G-->A transition at nucleotide 20210, is a risk factor for venous thrombosis in heterozygotes and is associated with increased prothrombin activity. The homozygous phenotype and the extent of thrombin generation in heterozygous and homozygous subjects are unknown. We investigated a family that included 2 homozygous and 5 heterozygous carriers of the 20210 A allele. The homozygous propositus and his presumably heterozygous father suffered from deep-vein thrombosis. His presumably heterozygous mother and his homozygous sister had recurrent phlebitis at a young age. The remaining 5 affected family members are still asymptomatic. We studied thrombin generation in the family and in 22 unrelated carriers of the 20210 A allele by measuring (1) prothrombin fragment F1+2 (F1+2) as an index of ongoing thrombin generation and (2) the endogenous thrombin potential (ETP) as an index of the possible thrombin-forming capacity. Their F1+2 levels were not different from those of age-matched controls, and thus, ongoing hemostatic system activation was not detectable. A significantly increased ETP was found in the heterozygous carriers of the 20210A allele compared with the controls (527.8+/-114.9 versus 387+/-50.1 nmol/L x min, P<0.0001). In the 2 homozygotes, the ETP was almost twice (639 and 751 nmol/L x min, respectively) as high as in the controls. We conclude that homozygosity for the G20210A mutation in the prothrombin gene is associated with a severe, albeit more benign, thrombotic diathesis compared with homozygosity for deficiencies of antithrombin, protein C, or protein S. In carriers of the 20210 A allele, the pathomechanisms leading to thrombosis should be sought in the higher amounts of thrombin that may be formed once thrombin generation is triggered, rather than in ongoing thrombin generation in vivo.

Brachytherapy for prophylaxis of restenosis after long-segment femoropopliteal angioplasty: pilot study.

PURPOSE: To evaluate in a pilot study the feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA) without stent implantation in a group of patients with a high risk of restenosis. MATERIALS AND METHODS: Ten patients (six women, four men; mean age, 68 years) with long-segment (mean length, 16 cm; range, 9-22 cm) restenosis underwent PTA followed by endovascular irradiation with high-dose-rate afterloading of an iridium-192 rod. A dose of 12 Gy was targeted to the inner intimal layer of the vessel. Follow-up examinations until 12 months after PTA included measurement of the ankle-brachial index, color duplex ultrasonography (US) with calculation of the peak velocity ratio, and intraarterial angiography when recurrence was suspected. RESULTS: Irradiation was technically feasible in all patients without complications. In six patients, the dilated and irradiated segment remained widely patent at color US, with corresponding excellent hemodynamic and clinical results after 12 months. In four patients, clinical and laboratory findings indicated recurrence and arteriography demonstrated restenosis with a diameter reduction of 60%, 70%, 80%, or 90%. CONCLUSION: Considering the negative selection of patients with a high risk of restenosis, the results of our pilot study are promising concerning the possibility of reduction of restenosis by means of endovascular brachytherapy after long-segment femoropopliteal PTA without stent implantation. The value of this approach should now be determined definitively in randomized trials.

Prothrombin fragment F1+2 is not predictive for recurrent venous thromboembolism.

It would be important to estimate in advance the risk of recurrent thrombosis. Deficiencies of antithrombin, protein C or protein S, or resistance to activated protein C are associated with a biochemically detectable prethrombotic state. It is thus far unknown whether in patients with a history of thromboembolism but without a defined clotting abnormality a heightened coagulation activation is detectable. We investigated the value of prothrombin fragment F1+2 (F1+2) as a predictor of recurrent venous thromboembolism. Furthermore, we compared the F1+2 levels of thrombosis patients without a defined clotting defect to those of Factor V Leiden patients with a history of venous thrombosis and to those of healthy controls. 180 patients without a defined clotting abnormality and 73 patients with Factor V Leiden were prospectively followed after discontinuation of oral anticoagulants for venous thrombosis and F1+2 was measured at regular intervals. Recurrent venous thromboembolism occurred in 23 (9%) of the 253 patients. Before or at several time points after oral anticoagulants, no significant difference in F1+2 levels was found in patients with and without recurrent thrombosis. F1+2 levels at 3 weeks and prior to recurrence were not significantly different in both patient groups. Over a one-year observation period, F1+2 levels of both patients with and without Factor V Leiden were higher than those of the controls. No difference in F1+2 was seen between patients with and without Factor V Leiden. We conclude that monitoring of F1+2 is not suitable for identification of individuals at risk of recurrent venous thrombosis. Permanent hemostatic system activation is detectable both in patients with a defined abnormality of the clotting system and in patients in whom a particular defect has not (yet) been identified.

Ultrasound guided compression therapy in 134 patients with iatrogenic pseudo-aneurysms: advantage of routine duplex ultrasound control of the puncture site following transfemoral catheterization.

BACKGROUND: The following study was designed to evaluate the effectiveness and safety of ultrasound guided compression therapy (UGCT) of iatrogenic postcatheterization pseudo-aneurysms (PA) on the one hand and to justify the usefulness of the routine colour duplex control of the puncture site following transfemoral catheterization, on the other hand. MATERIAL AND METHODS: During the study period 142 patients with (PA) following transfemoral catheterization were identified by means of colour duplex examination Eighty of these 142 patients were identified during a routine colour duplex control of the puncture site the day after PTA/angiography because of peripheral arterial occlusive disease (PAOD) [group A]; the remaining 62 patients with symptomatic groins were referred from other departments [group B]. RESULTS: In 8 patients of group B UGCT was considered to be contra-indicated, they were primarily treated by surgical repair of the PA. A total of 134 patients (group A 80 patients, group B 54 patients) underwent an UGCT. In total the success rate of UGCT was in group A 100% and in group B 78%. 12/54 patients (all group B) with failure of UGCT underwent a secondary surgical repair of the PA. Within group B there was a negative correlation between delay of diagnosis/UGCT and success (p < 0.04), whereas the size of the sheath did not influence the outcome of the UGCT (p = 0.3). CONCLUSION: Our study confirms the effectiveness and safety of UGCT. Routine colour duplex control of the puncture site the day following the removal of the sheath after percutaneous catheterization and UGCT of PAs without delay can increase the success rate of UGCT and minimize the need for surgical repair of PAs.

Value of color duplex sonography for evaluation of tibioperoneal arteries in patients with femoropopliteal obstruction: a prospective comparison with anterograde intraarterial digital subtraction angiography.

PURPOSE: This study investigated the accuracy of color duplex sonography (CDS) compared with anterograde intraarterial digital subtraction angiography in the evaluation of the tibioperoneal arteries in patients with peripheral arterial occlusive disease. METHODS: Fifty consecutive patients with femoropopliteal obstruction were examined immediately before planned percutaneous transluminal angioplasty. All CDS examinations were performed by one observer; the angiograms were interpreted independently by two readers (A1, A2). We compared agreement concerning judgement of the dominant crural artery (suitable for an eventual femorocrural bypass operation) and judgement of the severity of arterial lesions. RESULTS: Concerning judgement of the dominant artery, the interobserver agreement between the two readers of the angiograms was better (kappa value, 0.76) than the agreement between CDS versus A1 (0.61) and CDS versus A2 (0.56). However, the differences were not statistically significant. The results were independent (no significant differences in the kappa values) of the following criteria: presence of diabetes; clinical stage of peripheral arterial occlusive disease; kind of femoropopliteal obstruction; and status of the popliteal artery. Concerning the evaluation of the severity of arterial lesions, the kappa values were significantly higher (p < 0.05) for A1 versus A2 (posterior tibial, 0.87; anterior tibial, 0.79; peroneal, 0.52) than for CDS versus A1 (0.51; 0.46; 0.07) and CDS versus A2 (0.35; 0.38; -0.05). The sensitivity of CDS (vs A1 as reference) for detecting a hemodynamically relevant arterial lesion (stenosis or occlusion) was 100% in the posterior tibial artery, 78% in the anterior tibial artery, and 92% in the peroneal artery. CONCLUSION: Compared with intraarterial anterograde digital subtraction angiography, the value of CDS-with its currently used technology-for evaluation of the dominant lower leg artery suitable for an eventual femorocrural bypass operation in patients who have femoropopliteal obstruction is limited. It cannot replace an accurate preoperative angiogram for the routine clinical practice, and its use should be restricted to special cases (such as patients with a history of severe allergic reaction to contrast media or of severely impaired kidney function). CDS is also limited in the accurate judgement of the morphologic features of the runoff arteries in their full length in patients with peripheral arterial occlusive disease.

The risk of recurrent venous thromboembolism in patients with and without factor V Leiden.

Thromboprophylaxis with oral anticoagulants up to six months is established in patients after a first venous thromboembolic event (VTE). The risk of recurrent VTE is still considerable thereafter, and it is uncertain whether some patients might benefit from extended anti-coagulation. We performed a prospective, multicenter trial (4 thrombosis centers) and evaluated in 380 patients with a first or recurrent VTE (patients with a deficiency of antithrombin, protein C, protein S or plasminogen; cancer; or an antiphospholipid antibody syndrome were excluded) the risk of recurrence after discontinuation of secondary thromboprophylaxis with oral anticoagulants. It was the aim of the study to evaluate whether patients, with factor V Leiden are at an increased risk of recurrent VTE. 112 (29.5%) patients were carriers of factor V Leiden (26.9% heterozygous, 2.6% homozygous). After a median observation time of 19.3 months the overall recurrence rate of VTE was 9.9%. Recurrent deep vein thrombosis and/or pulmonary embolism occurred in 26 of 268 patients without factor V Leiden (9.7%) and in 10 of 112 patients with factor V Leiden (8.9%). The probability of recurrent VTE two years after discontinuation of oral anticoagulants was 12.4% (95% CI 7.8-17) in patients without factor V Leiden and was 10.6% (95% CI 3.8-17.4) in carriers of the mutation. This difference was statistically not significant. Patients with factor V Leiden are not at a higher risk of recurrent VTE within two years after discontinuation of oral anticoagulants than patients without factor V Leiden. Balancing the risk of recurrent VTE and bleeding from oral anticoagulants, patients with factor V Leiden are not likely to benefit from oral anticoagulant therapy extended beyond six months.

Thromboembolic complications in a patient with heparin-induced thrombocytopenia (HIT) showing cross-reactivity to a low molecular weight heparin-treatment with Org 10172 (Lomoparan).

Heparin-induced thrombocytopenia is an immuno-mediated life-threatening side effect of heparin therapy which poses difficulties in diagnosis and major therapeutic problems. Heparin must be instantly discontinued. We describe the case of a 60-year-old male patient with type II heparin-induced thrombocytopenia, complicated by progressive deep venous thrombosis and pulmonary embolism. He failed to improve when therapy was continued with a low molecular weight heparin (Fragmin) and high doses of intravenous immunoglobulins were administered. The test for heparin-dependent platelet aggregation was positive for unfractionated heparin and low molecular weight heparin, but negative for the heparinoid Org 10172. During subsequent anticoagulant therapy with Org 10172 for seven days the number of platelets increased rapidly and the patient recovered. Nine months later Org 10172 was used again in this patient for thrombosis prophylaxis without any adverse effects. In patients with heparin-induced thrombocytopenia requiring immediately acting anticoagulant therapy, Org 10172 can be considered as an effective alternative drug to unfractionated and low molecular weight heparins.

Levels of prothrombin fragment F1+2 in patients with hyperhomocysteinemia and a history of venous thromboembolism.

Increased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment F1+2 (F1+2) was determined in the patient's plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher F1+2 levels than patients without H-HC (mean 0.52 +/- 0.49 nmol/l, median 0.4, range 0.2-2.8, versus 0.36 +/- 0.2 nmol/l, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3, 6, 9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher F1+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either F1+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated F1+2 level(s) followed by recurrent VTE. No statistical significant difference in the F1+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.

Elevated lipoprotein(a) and increased incidence of restenosis after femoropopliteal PTA. Rationale for the higher risk of recurrence in females?

It has been shown that the incidence of recurrent stenosis following successful percutaneous transluminal coronary angioplasty (PTCA) is correlated with serum Lipoprotein(a) [Lp(a)] levels. The aim of the present study was to examine the influence of Lp(a) on restenosis after primary successful femoropopliteal PTA. One hundred and thirty nine consecutive patients with peripheral arterial occlusive disease (PAOD) and successful femoropopliteal PTA were studied. Follow-up included clinical examination and non-invasive laboratory testing (pulse volume recordings, ankle-brachial arterial pressure measurement) in every patient before and after 1, 3, 6 and 12 months following intervention. Duplex sonography was performed 1 year after PTA. Suspicion of restenosis (> or = 50% diameter reduction) was verified by angiography. Lp(a) was determined using ELISA technique (mg/dl). Twelve months after successful PTA no restenosis was found in 82 patients (59%: group A). The one-year recurrence rate of 41% (group B) was due to significant restenosis in 35 patients (25%) and reocclusion in 22 patients (16%). The corresponding mean values +/- S.E.M. for Lp(a) were as follows: group A, 28 +/- 5.3; group B 59 +/- 11 (P < 0.01). Women showed a higher frequency of recurrences (55%) versus men (30%, P < 0.01) also corresponding with a high Lp(a) level (51.8 +/- 8 versus 32.7 +/- 5; P < 0.05). Furthermore Lp(a) aggravated the well known increased risk for recurrence in multiple stenoses or occlusions of > or = 5 cm in length. There were no significant differences between groups A and B with respect to age, diabetes, hyperlipidaemia, obesity and cigarette smoking. The results support the view that Lp(a) is an independent risk factor for recurrence after PTA in the femoropopliteal area. It might also be a causal basis for the higher incidence of recurrences in female PAOD patients.

Effect of detailed fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congenital heart disease.

BACKGROUND: Cardiac abnormalities are frequently not detected by routine ultrasound screening examinations. Although detailed fetal echocardiography is more sensitive in detection of congenital heart disease, it is used only for high-risk cases. The main aim of this study was to assess the prenatal detection of congenital heart disease by detailed fetal echocardiography in an unselected, consecutive group of pregnant women. METHODS: Between Jan 1, 1993, and Sept 30, 1994, all women who attended our antenatal-care unit were routinely offered a detailed fetal echocardiography examination at 18-28 weeks' gestation. 3085 consecutive women were screened: 2181 were screening cases with no known risk factor for congenital heart disease; 540 had maternal risk factors for congenital heart disease, such as a family history or coexisting maternal disease; 364 had sonographically detected abnormalities. The examination included the four-chamber view, outflow-tract scan, and colour-flow mapping; doppler and M-mode investigations were also done when appropriate. FINDINGS: 46 cases of congenital heart disease were detected prenatally by echocardiography-15 in the group with no risk factors, three in the group with maternal risk factors, and 28 in the group with sonographic abnormalities. Postnatal assessments found six further cases of congenital heart disease that had not been detected prenatally, but these were all minor cases. There were no false-positive diagnoses (sensitivity 85.5%, specificity 100%). The incidence of congenital heart disease in screening cases with no risk factors and in those with maternal risk factors was low (6.9% per 1000, 5.6 per 1000) and similar to the expected overall incidence of 8.0 per 1000 livebirths in the general population. In the group with sonographic abnormalities congenital heart disease was found significantly more often (79.9 per 1000). INTERPRETATION: Inclusion of detailed fetal echocardiography as a screening examination has a substantial effect on detection of congenital heart disease since a major proportion of prenatally detectable cases occur in a low-risk population.

Tissue concentration of clindamycin and gentamicin near ischaemic ulcers with transvenous injection in Bier's arterial arrest.

BACKGROUND: In the treatment of patients with inflamed ischaemic ulcers in peripheral arterial occlusive disease, high tissue concentrations of antibiotics (TCA) are important. With local transvenous pressure injection in Biers' arterial arrest (TVA-Bier) higher TCAs are assumed to be obtained but they have not been measured. METHODS: Two groups of 16 patients each with ischaemic foot ulcers were studied. In one group, patients received a mean of 284 (SD 116) mg gentamicin and in the other, 1200 mg clindamycin. The antibiotics were given intravenously, intra-arterially, and by TVA-Bier in a randomised order at intervals of 48 hours. Biopsy samples were taken from the edge of the ulcers 20 minutes and 3 hours after TVA-Bier, and 1 hour and 3 hours after intravenous and intra-arterial injection. At the same times blood samples were taken. FINDINGS: TCAs of gentamicin and clindamycin with TVA-Bier were significantly higher compared with intravenous or intra-arterial injection. Median TCA-enhancing factor of clindamycin achieved by TVA-Bier at 20 min 1 hour was 18.3 and 14.1 versus intravenous and intra-arterial infusion, respectively, and at 3 hours 7.3 and 5.6, respectively. The median TCA-enhancing factor for gentamicin by TVA-Bier versus intravenous and intra-arterial application was, at 1 hour 20 min, 9.4 and 9.7, respectively, and at 3 hours 1.2 and 1.7, respectively. INTERPRETATION: Higher TCAs could be achieved with TVA-Bier than with intravenous or intra-arterial infusion. TCAs were lower when using gentamicin and higher with clindamycin.