Indirect effect of IGF2 intron3 g.3072G>A mutation on prolificacy in sows.

A QTL located in the paternally expressed insulin-like growth factor 2 (IGF2) gene is known to increase muscle growth and reduce fat deposition in pigs. This makes the QTL in IGF2 a good marker for use in pig breeding programmes. However, care has to be taken as it is postulated that increased leanness and lowered fat deposition may have a negative effect on the prolificacy and longevity of sows. Selection of sire and dam lines for different alleles of the mutation in the paternally imprinted IGF2 gene could actually provide a solution to this problem. Therefore, in this study, the effect of the IGF2 QTL on prolificacy-related traits in sows was investigated. It was found that the paternal IGF2 wild-type allele was associated with higher reproduction performance in the sow. Moreover, it was also examined whether the difference in prolificacy in sows could be a consequence of differential IGF2 expression in the ovarian follicles of the sow or whether it is mainly a secondary effect caused by differences in fatness traits. Therefore, IGF2 expression was measured in follicles of different sizes from sows with different genotypes for the paternal IGF2 allele. It was observed that, however, while the size of the follicles was associated with follicular IGF2 expression level, the IGF2 genotype was not. It could be concluded that the difference in prolificacy of sows with a different paternal IGF2 genotype could be a secondary effect, resulting from differences in fat deposition.

Spinal cord stimulation for ischemic heart disease and peripheral vascular disease.

Ischemic disease (ID) is now an important indication for electrical neuromodulation (NM), particularly in chronic pain conditions. NM is defined as a therapeutic modality that aims to restore functions of the nervous system or modulate neural structures involved in the dysfunction of organ systems. One of the NM methods used is chronic electrical stimulation of the spinal cord (spinal cord stimulation: SCS). SCS in ID, as applied to ischemic heart disease (IHD) and peripheral vascular disease (PVD), started in Europe in the 1970s and 1980s, respectively. Patients with ID are eligible for SCS when they experience disabling pain, resulting from ischaemia. This pain should be considered therapeutically refractory to standard treatment intended to decrease metabolic demand or following revascularization procedures. Several studies have demonstrated the beneficial effect of SCS on IHD and PVD by improving the quality of life of this group of severely disabled patients, without adversely influencing mortality and morbidity. SCS used as additional treatment for IHD reduces angina pectoris (AP) in its frequency and intensity, increases exercise capacity, and does not seem to mask the warning signs of a myocardial infarction. Besides the analgesic effect, different studies have demonstrated an anti-ischemic effect, as expressed by different cardiac indices such as exercise duration, ambulatory ECG recording, coronary flow measurements, and PET scans. SCS can be considered as an alternative to open heart bypass grafting (CABG) for patients at high risk from surgical procedures. Moreover, SCS appears to be more efficacious than transcutaneous electrical nerve stimulation (TENS). The SCS implantation technique is relatively simple: implanting an epidural electrode under local anesthesia (supervised by the anesthesist) with the tip at T1, covering the painful area with paraesthesia by external stimulation (pulse width 210, rate 85 Hz), and connecting this electrode to a subcutaneously implanted pulse generator. In PVD the pain may manifest itself at rest or during walking (claudication), disabling the patient severely. Most of the patients suffer from atherosclerotic critical limb ischemia. All patients should be therapeutically refractory (medication and revascularization) to become eligible for SCS. Ulcers on the extremities should be minimal. In PVD the same implantation technique is used as in IHD except that the tip of the electrode is positioned at T10-11. In PVD the majority of the patients show significant reduction in pain and more than half of the patients show improvement of circulatory indices, as shown by Doppler, thermography, and oximetry studies. Limb salvage studies show variable results depending on the stage of the trophic changes. The underlying mechanisms of action of SCS in PVD require further elucidation.

[Intraoperative MRI in brain surgery]. / Intraoperatieve MRI bij hersenchirurgie.

Neuronavigation is a frequently used method in the planning of intracranial neurosurgical procedures. During surgery however, due to anatomical changes such as loss of cerebrospinal fluid, tumour resection and oedema, preoperative data become inaccurate. Updated data acquisition during the procedure using intraoperative MRI (iMRI) overcomes this problem, as it enables maximum tumour resection or accurate tumour biopsy, whilst minimizing the risk of damaging healthy brain tissue. The choice between low field and high field strength systems depends on the desired image quality and integration into the regular workflow. In spite of its high costs, iMRI surgery seems to be cost-effective, due to reduced length of hospital stay, reduced repeat resection, and reduced hospital charges. In the future, intraoperative imaging combined with virtual planning stations, is expected to play an important role in implementing robotization into neurosurgery.

Placebo controlled utility and feasibility study of the H-reflex and flexor reflex in spastic children treated with intrathecal baclofen.

OBJECTIVE: To evaluate feasibility and utility of the soleus H-reflex and tibialis anterior flexor reflex (FR) in identifying spinal cord neuronal response to intrathecal baclofen (ITB) in children with severe spastic cerebral palsy. METHODS: During a randomized, double-blind, placebo-controlled dose-escalation test treatment, maximum H amplitude/maximum M amplitude (H/M ratio) and FR parameters were bilaterally recorded at baseline and 2-3 h after intrathecal bolus administration of placebo and increasing doses of baclofen until both an improvement in the individual treatment goal(s) and a one-point reduction on the Ashworth scale were observed. RESULTS: Electrophysiological data of 14 children were studied. The H-reflex was feasible in 13 children, the FR threshold area in 9 and the FR, elicited with supramaximal stimulation, in only one child. After ITB, the H/M ratio significantly decreased (left: 0.67+/-0.47 to 0.15+/-0.18, P=0.005; right: 0.55+/-0.32 to 0.14+/-0.19, P=0.002) without placebo effect. FR threshold area after ITB, only decreased significantly in children not taking oral baclofen (left: 146+/-53 to 41+/-54 mV ms, P=0.000; right: 156+/-80 to 66+/-48 mV ms, P=0.002). CONCLUSIONS: This is the first randomized, double-blind, placebo-controlled dose-escalation study in spastic children demonstrating the soleus H-reflex to be a feasible and objective measure to quantify the decreasing motoneuron excitability in response to ITB bolus administration. Only in children not taking oral baclofen, FR threshold area can also be used as an objective outcome measure, yet feasibility is limited. SIGNIFICANCE: We suggest introducing the H-reflex as the electrophysiological gold standard for the evaluation of the effect of ITB in spastic children.

The use of an indium111 DTPA flow study in the evaluation of a lumbar swelling in a girl with a baclofen pump.

OBJECTIVE: The aim of this study was to introduce a useful diagnostic method to evaluate baclofen pump system-related complications without disturbing the continuous delivery of intrathecal baclofen. METHODS: We present a case report on the use of an indium (111) diethylenetriaminepentaacetic acid (DTPA) flow study in the evaluation of a lumbar swelling in a 16-year-old girl with spastic cerebral palsy, treated with continuous intrathecal baclofen (CITB). RESULTS: Disconnection or damage of the catheter leading to leakage of baclofen into the lumbar swelling could be ruled out by the use of an indium (111) DTPA flow study. This is the first report to illustrate the implementation of an lndium (111) DTPA flow study without interrupting the infusion of CITB. CONCLUSION: An indium (111) DTPA flow study is a non-invasive, safe and patient friendly diagnostic method which can be of great help in the evaluation of pump- or catheter-related complications and does not need to interfere with the delivery of CITB.

Systematic review and meta-analysis of controlled trials assessing spinal cord stimulation for inoperable critical leg ischaemia.

BACKGROUND: Spinal cord stimulation (SCS) may have a place in the treatment of patients with inoperable chronic critical leg ischaemia. METHODS: A systematic review and meta-analysis was performed of all controlled studies comparing SCS in addition to any form of conservative treatment for inoperable chronic critical leg ischaemia. Main endpoints were limb salvage, pain relief and clinical situation. Systematic methodological appraisal and data extraction were performed by independent reviewers. RESULTS: Of the 18 reports found, nine trials, comprising 444 patients, matched the selection criteria. After pooling, limb salvage at 12 months appeared significantly greater in the SCS group (risk difference (RD) -0.13 (95 per cent confidence interval (c.i.) -0.04 to -0.22)). Significant pain relief occurred in both treatment groups, but patients who received SCS required significantly less analgesia and reached Fontaine stage 2 more often than those who did not have SCS (RD 0.33 (95 per cent c.i. 0.19 to 0.47)). Complications of SCS were problems of implantation (8.2 per cent), changes in stimulation requiring reintervention (14.8 per cent) and infection (2.9 per cent). CONCLUSION: The addition of SCS to standard conservative treatment improves limb salvage, ischaemic pain and the general clinical situation in patients with inoperable chronic critical leg ischaemia. These benefits should be weighed against the cost and the (minor) complications associated with the technique.

Management of hardware infections following deep brain stimulation.

OBJECTIVE: To report our experience on hardware-related infections following deep brain stimulation (DBS). METHODS: The present article presents the retrospective clinical notes review of gained in a two-centre, single-surgeon study experience of 108 consecutive DBS cases between 1996 and 2002. In all patients the minimum follow-up was six months. One hundred and eight patients received an intracerebral electrode implantation and 106 underwent internalization. RESULTS: In total 178 electrodes were implanted with a mean follow-up of 42.6 months and a cumulative follow-up of 367.7 patient-years. Four patients (3.8%) developed an infection related to the DBS-hardware and all were initially treated with antibiotics. Two patients eventually required additional surgical treatment. CONCLUSION: Infections due to DBS-hardware can result in considerable levels of morbidity. In certain cases antibiotic therapy may be adequate. In others, surgical intervention to externalise the electrodes may be necessary. In our experience, there was never a need to remove the electrodes.

Treatment of cerebellar hematoma in The Netherlands. A questionnaire survey.

A questionnaire was sent to Dutch neurosurgeons and neurologists in order to assess current management strategies for cerebellar hematoma. Seven patients were presented, using as determinants: size of hematoma, coma score, interval to clinical deterioration, hydrocephalus, comorbidity, anticoagulant treatment and age. Neurological management options were: no treatment, monitoring or referral for neurosurgery. Neurosurgical options were: no treatment, monitoring, hematoma evacuation, and/or external ventricular drainage. Ninety-seven of 161 (60%) neurologists, and 58 of 85 neurosurgeons (68%) responded. Only 20 respondents (13%) made use of a local guideline. Overall agreement was perfect in 1 case and moderate to high in the others, but chance-adjusted agreement (kappa) between pairs of neurologists and neurosurgeons who were matched for referral center was not statistically significant except in 1 case, a deeply comatose patient with a 4-cm hematoma. In an alert, slightly ataxic patient with a large (4.5-cm) hematoma, 84 neurologists (88%) decided not to refer the patient. The estimated time for transfer between centers was of no influence on this decision. We conclude that the management of cerebrellar hematoma can be improved upon by encouraging the use of local guidelines, and by promoting early referral to a center with neurosurgical facilities.

The results of spinal cord stimulation in critical limb ischaemia: a review.

OBJECTIVES: to determine which patients with unreconstructible critical limb ischaemia (CLI) might benefit from spinal cord stimulation (SCS). METHODS: literature review. RESULTS: limb salvage in patients with an intermediate transcutaneous oxygen pressure (TcpO2) was not significantly higher with SCS (76%) than with conservative therapy (p=0.08). However, a limb salvage of 88% was achieved with SCS if the difference between the supine and sitting TcpO2 baseline values (DeltaTcpO2) was > or =15 mmHg. A rise in TcpO2 after trial stimulation of at least 15% resulted in a limb salvage of 77% at 18 months (p<0.01). CONCLUSION: randomised studies show no benefit of SCS over conservative therapy in patients with non-reconstructible CLI. However, data from experimental and non-randomised studies suggest this may be due to sub-optimal patient selection for SCS. Further trials are needed to identify subgroups who may benefit from SCS.

Pain and quality of life in patients with critical limb ischaemia: results of a randomized controlled multicentre study on the effect of spinal cord stimulation. ESES study group.

We carried out an assessment of pain and quality of life of patients with critical limb ischaemia during the follow-up of a multicentre randomized trial in more detail than previously reported. In a multicentre clinical trial 120 patients were randomized between medical treatment and medical treatment plus spinal cord stimulation. Patients were selected on the basis of clinical symptoms and macrocirculatory data as described in the European consensus document on critical limb ischaemia. Data were collected at intake and then 1, 3, 6, 12 and 18 months later. Primary outcome measures were limb salvage, pain relief and quality of life. Patient and limb survival was estimated with the Kaplan-Meier method. Pain was evaluated using the visual analogue scale (VAS), the McGill pain questionnaire, the pain score of the Nottingham Health Profile (NHP) and the use of analgesics. Quality of life was evaluated using the NHP, the EuroQol and mobility subscore of the Sickness Impact Profile. The 2-year limb survival was 52% for SCS treatment and 46% for standard treatment (p =0.47). Pain relief was considerable in both treatment strategies (p<0.005) with no significant differences between the strategies. The improvement occurred within the first few months and remained stable during further follow-up. Patients with SCS used fewer non-narcotic and narcotic drugs (p<0.001 at t=1 and t=3, p<0.002 at t=6). The overall scores of quality of life improved significantly (p<0.05), with no difference in score between treatments. The subscores of mobility and energy of the NHP in non-amputated patients was significantly better in the SCS group (p<0.005). Amputation had a negative effect on mobility, resulting in a difficult rehabilitation but relieved pain substantially (p<0. 05). In contrast to the existing literature, the randomized trial revealed no major difference in overall pain and quality of life assessment between treatment groups. The effect on energy and mobility was significantly better in patients treated with SCS, who also used substantially fewer analgesics.

Technical data and complications of spinal cord stimulation: data from a randomized trial on critical limb ischemia.

This study was done to evaluate the effect of spinal cord stimulation (SCS) on critical limb ischemia and to report technical problems and complications. One hundred and twenty patients with critical limb ischemia were eligible for randomization between medical treatment and medical treatment plus SCS. Sixty received a spinal cord stimulator (Itrel II; Medtronic, Minneapolis, Minn., USA). Primary outcome measures were limb salvage and pain relief. The mean pain reduction in both treatment groups was 50% (from 5 to 2.5 on the visual analog scale). The 2-year limb survival was 52% (SCS) versus 46% (standard treatment; p = 0.47). The number of patients undergoing major amputations in the SCS group with intermediate TcpO2 values was half of that in the standard group (14 vs. 28; 24 vs. 48%; p = 0.17). Implantation was successful in 51 patients. Technical problems such as loss of stimulation due to lead displacement occurred in 13 patients (22%), local infection at the site of implantation occurred in 3 patients (5%), resulting in a total complication rate of 27%. Premature depletion of the battery occurred within 2 years in 3 patients (5%). There were no lead fractures, epidural infections, hematoma or cerebrospinal fluid leakage. Training of physicians and better reliability of the hardware should reduce the frequency of technical problems. Lead displacement remains the major technical problem. The search for prognostic factors of limb salvage is important. One microcirculatory measurement (TcpO2) seems to have a prognostic value, which remains to be described more precisely.

Microcirculatory investigations to determine the effect of spinal cord stimulation for critical leg ischemia: the Dutch multicenter randomized controlled trial.

PURPOSE: Patients with non-reconstructable critical limb ischemia generally undergo medical treatment only to prevent or postpone amputation. There is some evidence that spinal cord stimulation (SCS) stimulates ischemic wound healing. Thus, this could benefit limb survival through improved skin perfusion. We investigated the effect of SCS versus conservative treatment on skin microcirculation in relation to treatment outcome in patients with non-reconstructable critical limb ischemia. METHODS: Standard medical treatment plus SCS was compared with only standard medical treatment in a multicenter randomized controlled trial comprised of 120 patients with surgically non-reconstructable chronic rest pain or ulceration. We investigated skin microcirculation by means of capillary microscopy, laser Doppler perfusion, and transcutaneous oxygen measurements in the foot. The microcirculatory status just before treatment was classified in three categories (poor, intermediate, and good) and was related to limb survival after a minimum follow-up period of 18 months. RESULTS: Clinical parameters, peripheral blood pressures, and limb survival rates showed no significant differences between the SCS and standard groups during the follow-up period. In both treatment groups, amputation frequency after 18 months was high in patients with an initially poor microcirculatory skin perfusion (SCS 80% vs standard treatment 71%; NS) and low in those with a good skin perfusion (29% vs 11 %, respectively; NS). In patients with an intermediate skin microcirculation amputation, frequency was twice as low in patients additionally treated with SCS as in the standard treatment group (48% vs 24%; P =.08). In these patients, microcirculatory reactive hyperemia during the follow-up period reduced in the standard group but not in the SCS group (P <.01). CONCLUSION: Selection on the basis of the initial microcirculatory skin perfusion identifies patients in whom SCS can improve local skin perfusion and limb survival.

Prediction of imminent amputation in patients with non-reconstructible leg ischemia by means of microcirculatory investigations.

PURPOSE: We investigated the usefulness of skin microcirculatory investigations to predict imminent major amputation in patients with non-reconstructible critical limb ischemia. METHODS: One hundred eleven patients with non-reconstructible chronic rest pain or small ulcers and an ankle blood pressure of 50 mm Hg or less or an ankle-to-brachial pressure index of 0.35 or less were included. Nailfold capillary microscopy (CM; big toe, sitting), transcutaneous oxygen pressure (TcpO2; forefoot, supine; 44 degrees C), and laser Doppler perfusion measurements (LD; pulp of big toe, supine) were performed at rest and during reactive hyperemia. Patients were classified according to their skin microcirculatory status just before the start of the treatment in three groups: those with a "good," "intermediate," or "poor" microcirculation, according to a combination of predefined cutoff values (Poor: capillary density less than 20/mm2, absent reactive hyperemia in CM and LD, TcpO2 less than 10 mm Hg; good: capillary density of 20/mm2 or more, present reactive hyperemia in CM and LD, TcpO 2 of 30 mm Hg or more). Subsequently, patients received maximum conservative therapy from the surgeon, who was unaware of the microcirculatory results. After a follow-up period of as long as 36 months, limb survival and disposing factors were analyzed and compared with the initial microcirculatory status. RESULTS: Cox regression analysis showed a significant prognostic value of the microcirculatory classification (hazard ratio = 0.28, P <.0001), but not of the Fontaine stage, ankle blood pressure, or the presence of diabetes mellitus for the occurrence of an amputation. Positive and negative predictive values were 73% and 67%, respectively. The cumulative limb survival at 6 and 12 months was 42% and 17% in the poor microcirculatory group, 80% and 63% in the intermediate microcirculatory group, and 88% and 88% in the good microcirculatory group ( P <.0001, log-rank). CONCLUSION: Microcirculatory screening and classification is useful in detecting non-reconstructible critical ischemia that requires amputation, which is not detectable by means of the clinical stage or blood pressure parameters. Most of the poor patient group will require amputation. In the intermediate and good groups, nonsurgical treatment appears sufficient for limb salvage.

Spinal-cord stimulation in critical limb ischaemia: a randomised trial. ESES Study Group.

BACKGROUND: For patients with critical limb ischaemia, spinal-cord stimulation has been advocated for the treatment of ischaemic pain and the prevention of amputation. We compared the efficacy of the addition of spinal-cord stimulation to best medical treatment in a randomised controlled trial. METHODS: 120 patients with critical limb ischaemia not suitable for vascular reconstruction were randomly assigned either spinal-cord stimulation in addition to best medical treatment or best medical treatment alone. Primary outcomes were mortality and amputation. The primary endpoint was limb survival at 2 years. FINDINGS: The mean (SD) age of the patients was 72.6 years (10.3). Median (IQR) follow-up was 605 days (244-1171). 40 (67%) of 60 patients in the spinal-cord-stimulator group and 41 (68%) of 60 patients in the standard group were alive at the end of the study, (p=0.96). There were 25 major amputations in the spinal-cord-stimulator group and 29 in the standard group, (p=0.47). The hazard ratio for survival at 2 years without major amputation in the spinal-cord stimulation group compared with the standard group was 0.96 (95% CI 0.61-1.51). INTERPRETATION: Spinal-cord-stimulation in addition to best medical care does not prevent amputation in patients with critical limb ischaemia.

Theoretical performance and clinical evaluation of transverse tripolar spinal cord stimulation.

A new type of spinal cord stimulation electrode, providing contact combinations with a transverse orientation, is presented. Electrodes were implanted in the cervical area (C4-C5) of two chronic pain patients and the stimulation results were subsequently simulated with a computer model consisting of a volume conductor model and active nerve fiber models. For various contact combinations a good match was obtained between the modeling results and the measurement data with respect to load resistance (less than 20% difference), perception thresholds (16% difference), asymmetry of paresthesia (significant correlation) and paresthesia distributions (weak correlation). The transversally oriented combinations provided the possibility to select either a preferential dorsal column stimulation, a preferential dorsal root stimulation or a mixed stimulation. The (a)symmetry of paresthesia could largely be affected in a predictable way by the selection of contact combinations as well. The transverse tripolar combination was shown to give a higher selectivity of paresthesia than monopolar and longitudinal dipolar combinations, at the cost of an increased current (more than twice).

Intracranial chondrosarcoma: review of the literature and report of 15 cases.

The available data in the literature (177 cases), two current clinical patients, and cases which occurred in The Netherlands (13) were reviewed concerning the clinical presentation, pathological features, radiological data, and treatment options of chondrosarcoma of the cranial base. The mean age of patients was 37 years, the male/female ratio 1:1.1. The most frequent complaints were diplopia with oculomotor disorders (51%), headache (31%), and decreased hearing, dizziness, and tinnitus with statoacusticus dysfunction (21%). The mean duration of symptoms before diagnosis was 27 months. The chondrosarcomas were located in the petrosal bone in 37% (47 cases), in the occipital bone and clivus in 23% (30 cases), in the sphenoid bone in 20% (25 cases) and to a lesser extent in frontal, ethmoidal, and parietal bones (14%). In 6% (eight cases) the primary location was in dural tissue. Radiological examinations showed bone destruction and variable calcification (CT), involvement of neuronal and vascular structures (MRI), and mostly hypovascularity on angiography. On histological examination 51% of tumours were classified as grade I, 11% grade II, 30% mesenchymal, and 8% myxoid. The mesenchymal type was the most malignant as illustrated by a strong tendency to intradural and cerebral growth and possibly occurrence in younger age groups. The treatment of choice until recently was surgery because of the critical location and local aggressive nature. Regrowth of tumour after surgery occurred in 53% of the patients (average after 32 months). Charged particle irradiation gave a five year survival of 83-94% and a local control rate of 78%-91%. Both in surgery and radiotherapy there is treatment related morbidity and mortality that should be considered when offering these therapies. Recent promising results imply that charged particle radiotherapy, in combination with surgery, may be the therapeutical choice of the future.

An evaluation of ultrasound and nuclear magnetic resonance spectroscopy to measure in vivo intramuscular fat content of longissimus muscle of pigs.

Intramuscular fat content (IMF) of longissimus muscle of pigs growing from approximately 20 to 100 kg was measured in vivo using biopsies after complete or localized anaesthesia, ultrasound and 1H nuclear magnetic resonance (NMR) technology. Three lines of pigs, with 60 animals each, were available. Biopsies were taken from the same pigs at 20, 60, and 100 kg, and fat was extracted for gravimetric determination. At 20 kg, ultrasound images were collected, and in vivo 1H NMR spectroscopy was applied. A-mode ultrasound measurements were collected at 60 and 100 kg. The overall mean value of IMF was 1.60 +/- .56% at 20 kg, 1.53 +/- .50% at 60 kg, and 1.71 +/- .60% at 100 kg. Interactions between lines and body weight were observed. No statistically significant differences were found between methods at 20 kg. No significant correlations were found between the A-mode ultrasound measurements and the mean values of the gravimetric measurements. No visible pain or infections were observed in relation to the collection of a single biopsy. The ultrasound method in combination with image analysis is advantageous from the labor point of view and will also improve welfare of pigs in case of repeated sampling. However, further research is necessary to make the technology sufficiently reliable. A correlation between IMF and backfat thickness was not found.

Design issues of a randomised controlled clinical trial on spinal cord stimulation in critical limb ischaemia. ESES Study Group.

OBJECTIVES: Review of the design of a clinical study to evaluate of the efficacy of epidural spinal cord electrical stimulation (ESES) as compared to best medical treatment in patients with nonreconstructible critical limb ischaemia. DESIGN: Randomised controlled clinical trial of pragmatic type, which will be analysed according to the intention-to-treat principle. The treatment strategies are ESES, in addition to best medical treatment, and best medical treatment alone. Patients are followed-up for at least 18 months. SETTING: The ESES-trial is an ongoing multicentre trial in 17 hospitals in The Netherlands. PATIENTS: Patients with critical limb ischaemia, nonsuitable for either primary intervention or reintervention after failing reconstructions. CHIEF OUTCOME MEASURES: Limb survival, patient survival, quality of life and cost-effectiveness. MAIN RESULTS: From November 1991 until May 1994 120 patients had been enrolled. Using life-table analysis, at one year 76% of these randomised patients were alive: 41% without amputation and 35% with amputation. Quality of life of the trial patients was low, even compared to other severely ill patient groups, such as liver and heart transplant candidates. CONCLUSIONS: Considering the high incidence of death and amputation, 18 months of follow-up seems adequate to detect a clinically relevant outcome improvement from ESES-treatment, if present. We hope to present the results of this study at the end of 1995.