Johan Thörne

Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease Effects of pyridoxine and folic acid treatment☆

Severe homocysteinemia due to genetic defects either of pyridoxal 5-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) or of enzymes in vitamin B12 and folate metabolism is associated with very early-onset vascular disease. Therefore, we studied homocysteine metabolism in 72 patients presenting before the age of 55 years with occlusive arterial disease of cerebral, carotid, or aorto-iliac vessels. Twenty patients (28%) had basal homocysteinemia; and 26 patients (36%) had abnormal increases of plasma homocysteine after peroral methionine loading, which exceeded the highest value for 46 comparable controls and was within the range for 20 obligate heterozygotes for homocystinuria due to CBS deficiency. Basal plasma homocysteine content was strongly and negatively correlated to vitamin B12 and folate concentrations. Plasma PLP was depressed in most patients but there was no correlation between PLP and homocysteine values. In 20 patients, treatment with pyridoxine hydrochloride (240 mg/day) and folic acid (10 mg/day) reduced fasting homocysteine after 4 weeks by a mean of 53%, and methionine response by a mean of 39%. These data show that a substantial proportion of patients with early-onset vascular disease have impaired homocysteine metabolism, which may contribute to vascular disease, and that the impaired metabolism can be improved easily and without side effects.

Abdominal aortic aneurysm with perianeurysmal fibrosis: Experience from 11 Swedish vascular centers ☆ ☆☆

Case records of 2026 patients operated on because of abdominal aortic aneurysms from 11 Swedish Vascular Centers were reviewed and revealed 98 cases (4.8%) of inflammatory abdominal aortic aneurysm. Also included in this case-control study was an analysis of a randomized group of 82 patients from the same centers who had noninflammatory abdominal aortic aneurysms. Four inflammatory aneurysms were ruptured, compared with 16 in the noninflammatory group (p less than 0.01). A higher proportion of patients with inflammatory abdominal aortic aneurysms had symptoms that led to radiographic investigations. The median erythrocyte sedimentation rate was 39 mm versus 19 mm (26% of patients with inflammatory abdominal aortic aneurysms had erythrocyte sedimentation rates greater than 50 mm; p less than 0.001), and the serum creatinine level was increased in 27 and 8 patients (p less than 0.01) in the inflammatory and noninflammatory groups, respectively. Preoperative investigations revealed ureteral obstruction in 19 patients with inflammatory abdominal aortic aneurysms, of whom 12 had preoperative nephrostomy or ureteral catheter placement. At operation, 20 additional patients exhibited fibrosis around one or both ureters. Although ureterolysis was performed in 19 patients, preoperative and postoperative creatinine levels did not differ between these patients and the conservatively treated ones. Duration of surgery (215 vs 218 minutes), intraoperative blood loss (2085 vs 2400 ml) and complications did not differ significantly between the groups. Overall operative (30-day) mortality was equal (11% vs 12%) but was increased for patients undergoing elective surgery for inflammatory abdominal aortic aneurysms (9% vs 0%; p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging and MR angiography of endoluminally treated abdominal aortic aneurysms.

OBJECTIVES To evaluate magnetic resonance imaging (MRI) with gadolinium-based contrast medium-enhanced MR angiography (MRA) for the follow-up of endoluminally treated abdominal aortic aneurysms. DESIGN MRI/MRA, angiography and computed tomography (CT) were performed 1 month after endoluminal stent-graft placement. MRI/MRA was repeated at 6 and 12 months and angiography and CT were added to confirm unexpected findings. MATERIALS Fifteen male patients with endoluminally treated abdominal aortic aneurysms. METHODS MRI with MRA, spiral CT with transverse images and angiography were performed. RESULTS MRI/MRA demonstrated changes of stent-graft morphology, aortic neck- and aneurysmal diameter, stent-graft blood flow, stent-graft leakage, blood flow in lumbar arteries, intra-aneurysmal thrombus, periaortic inflammation and vertebral body infarction. For most of these features MRI/MRA provided more information than angiography and/or CT. MRI was the only method demonstrating thrombus reorganisation and vertebral body infarction. CONCLUSIONS MRI with MRA provides the relevant information needed for follow-up of endoluminally treated abdominal aortic aneurysms (AAA). This may be the method of choice because of its use of contrast media with very low nephrotoxicity, lack of ionising radiation and non-invasiveness.

Biological responses differ considerably between endovascular and conventional aortic aneurysm surgery

OBJECTIVES To determine the inflammatory responses in endovascular abdominal aortic aneurysm (AAA) repair and their relation to clinical findings. DESIGN Prospective non-randomised study. SETTING University Hospital, Department of Surgery. PATIENTS AND METHODS Seven patients treated with an endoluminal procedure (AAA-E) and seven patients undergoing conventional surgery (AAA-C) were included. Inflammatory parameters were assessed by measurements of the cytokines interleukin (IL)-1 beta, IL-6, IL-8 and Tumour Necrosis Factor-alpha (TNF-alpha); analyses of complement proteins C1q, C4, C3, C5a and Terminal Complement Complexes (TCC); haematologic parameters and determination of C-reactive protein (CRP). RESULTS In six of seven patients in the AAA-E group blood pressure decreases were recorded during introduction of the device. IL-6 and CRP levels were found to be significantly higher in AAA-C patients compared to the AAA-E group. On the other hand, high TNF-alpha levels were recorded in the AAA-E group. Less consumption of the complement proteins C1q, C4 and C3 was observed in AAA-E compared to AAA-C patients. Increased C5a levels were recorded in the AAA-C group, whereas only slight fluctuations were noticed in the AAA-E group. TCC levels were unchanged in both groups. CONCLUSION Endovascular aortic aneurysm repair induced a significant inflammatory response, mainly involving TNF-alpha and differing from the findings during open AAA repair. These inflammatory responses were probably related to blood pressure decreases during the procedures. On the other hand, conventional repair induced responses related to the more extensive surgical trauma and reperfusion injury.

Factors related to outcome of neuroischemic/ischemic foot ulcer in diabetic patients

OBJECTIVES Peripheral vascular disease (PVD) is an important limiting factor for healing in neuroischemic or ischemic diabetic foot ulcer. The purpose of this study was to identify factors related to healing in patients with diabetes with foot ulcers and severe PVD. METHODS Patients with diabetes with a foot ulcer, consecutively presenting at a multidisciplinary foot center with a systolic toe pressure <45 mm Hg or an ankle pressure <80 mm Hg were prospectively included, followed according to a preset program, and with the exception of specified exclusions, subjected to angiography offered vascular intervention when applicable. All patients had continuous follow-up until healing or death irrespective of the type of vascular intervention. RESULTS One thousand one hundred fifty-one patients were included. Eighty-two percent had a toe pressure <45 mm Hg and 49% had an ankle pressure <80 mm Hg. Eight hundred one patients (70%) underwent an angiography. Out of these, 63% had vascular intervention, either percutaneous transluminal angioplasty (PTA; 39%) or reconstructive surgery (24%). Nine percent of the patients had one or more complications after angiography. PTA was multisegmental in 46% and to the crural arteries in 46%. Reconstructive surgery was distal in 51%. Age (P < .001), renal function impairment (P = .005), congestive heart failure (P = .01), number and type of ulcer (P < .001), and severity of PVD (P = .003) affected the outcome of ulcers. PTA and reconstructive vascular surgery increased the probability of healing without amputation (odds ratio [OR], 1.77 and 2.05, respectively). CONCLUSION Probability of ulcer healing is strongly related to comorbidity, extent of tissue involvement, and severity of PVD in patients with diabetes with severe PVD.

Surgical treatment versus thrombolysis in acute arterial occlusion: A randomised controlled study

Thrombolytic treatment has been tried in various forms for acute limb ischaemia with varying degrees of success but is also often accompanied by bleeding problems. The present investigation compares the effect of surgical thrombectomy (TE) and thrombolysis (TL) using recombinant tissue plasminogen activator (rt-PA). Twenty patients with a need for intervention owing to ischaemia lasting more than 24 h but less than 14 days were included. Patients randomised to TE were operated under epidural anaesthesia and patients in the TL group received 30 mg rt-PA during a 3 h period through a catheter placed into the thrombus and advanced as lysis was achieved. Thrombectomy resulted in an immediate restitution of blood flow in six out of nine cases, in three cases a bypass procedure was performed, and one of these failed with a resultant amputation. Thrombolysis gave a good primary result in six cases which lasted in four of them. Three had a subsequent percutaneous transluminal angioplasty. Partial lysis was seen in two cases and a further two failed. Five went to surgery with three bypass and two fogarty procedures being necessary. There was no hospital mortality and there were no bleeding complications due to the rt-PA treatment in this series. In 19 out of 20 patients the circulation was re-established. Appropriate handling of acute ischaemic conditions implies the use of both thrombolysis and appropriate surgical procedures, including distal bypass grafts.

Nitric oxide inhalation decreases pulmonary platelet and neutrophil sequestration during extracorporeal circulation in the pig

OBJECTIVE The inhibiting effect of nitric oxide on the aggregation and adhesion of neutrophils and platelets has been well documented in vitro. In vivo evidence, however, is more scant. In this study, we studied the effects of inhaled nitric oxide on pulmonary cellular sequestration in our sham hemodialysis model. Accumulation of neutrophils and platelets in the lungs has been shown to be an early event in this model. DESIGN Prospective, randomized, controlled study. SETTING Animal laboratory at a university medical center. SUBJECTS Twenty-six anesthetized, mechanically ventilated pigs. INTERVENTIONS 111Indium-oxine was used to selectively label neutrophils or platelets and the activity over the lungs was followed dynamically with a gamma camera. Sham hemodialysis, using a cuprophan hollow-fiber dialyzer, was instituted via catheters in the femoral vessels. The animals were divided into two main groups: a) the nitric oxide recipient group (n = 12, with platelets labeled in seven animals and neutrophils labeled in five animals); and b) the control group (n = 14, with platelets labeled in seven animals and neutrophils labeled in seven animals). The animals in the former group were given 50 parts per million of nitric oxide in the inspiratory gas from the beginning of dialysis and for 30 mins onward. MEASUREMENTS AND MAIN RESULTS Inhalation of nitric oxide attenuated the increase in activity over the lungs in both the neutrophil and platelet groups during sham hemodialysis. In addition, an inhibiting effect on the increase in pulmonary pressure was noted. CONCLUSION Apart from the effects of nitric oxide on central hemodynamics in this model, the scintigraphic findings indicate an in vivo effect of nitric oxide on the accumulation of platelets and neutrophils in the lungs, probably due to inhibition of the adhesion and/or aggregation of these cells.

Outcome of Ischemic Foot Ulcer in Diabetic Patients Who Had no Invasive Vascular Intervention

OBJECTIVE/BACKGROUND There is limited information regarding outcome in patients not available for revascularisation. Our aim was to identify factors related to ulcer healing in diabetic patients with severe peripheral arterial disease who were not available for revascularisation. METHODS Diabetic patients with a foot ulcer, consecutively presenting at a multidisciplinary foot centre with systolic toe pressure <45 mmHg or an ankle pressure <80 mmHg were prospectively included. Patients who received revascularisation were excluded. All patients had continuous follow-up until healing or death. RESULTS Out of 602 patients (median age: 76 years) included in this study, 50% healed either primarily (76%) or with a minor amputation (24%). Seventeen percent of patients healed after major amputation and 33% died unhealed. By regression analysis, rest pain, impaired renal function, ischemic heart disease, cerebral vascular disease, extent of tissue destruction, and ankle pressure >50 mmHg affected the outcome of the ulcers. CONCLUSION Diabetic patients with ischemic foot ulcers not available for revascularisations are not excluded from healing without major amputation. Factors strongly related to outcome were co-morbidity, severity of peripheral arterial disease, and extent of tissue destruction. Our findings reinforce the need for a classification system considering these factors at decision-making for vascular intervention.

Immune response to collagen impregnated Dacron double velour grafts for aortic and aorto-femoral reconstructions

This study presents 20 patients, randomised to receive either a collagen-treated or an ordinary Dacron graft for aortic reconstructions, and the results of a skin-prick test, blood parameters and ELISA for anti-collagen antibodies as well as NMR pictures during a 6 week follow-up period. Forty per cent (4/11) of those receiving a collagen impregnated graft had a significantly increased titre of antibodies and NMR revealed in two out of 11 patients either a slightly increased amount of fluid or fibrosis around the graft, both collagen impregnated. No differences were found between the graft groups concerning body temperature and leucocyte or platelet counts. The skin-prick test for collagen was negative in all cases.

Elastic properties of the lung and the chest wall in young and adult healthy pigs

Understanding of the elastic pressure/volume (Pel/V) curve is still limited in health and disease. The aim of the present study was to elucidate the Pel/V curve and elastance of the respiratory system (ERS) lung (EL) and chest wall (ECW) in healthy pigs. Six young (20.8 kg) and seven adult (58.9 kg), anaesthetized, paralysed and ventilated pigs were studied. Pel/V curves were recorded at zero end-expiratory pressure (ZEEP) and at positive end-expiratory pressure (PEEP) up to 40 cmH2O with a computer controlled ventilator during an insufflation at a low, constant flow. Pel/V curves of the respiratory system showed a complex pattern in both young and adult pigs. During the insufflation, ERS decreased, increased, fell, and increased again. A second Pel/V curve recorded immediately after the first one showed lower elastance and only one early fall in ERS. ECW fell over the initial segment and was then nearly stable. Difference between 1st and 2nd curves reflected changes in EL caused by recruitment during the 1st insufflation. At PEEP, such signs of collapse and recruitment were reduced. A strong tendency to lung collapse contributes to a complex pattern of elastic pressure/volume curves. At low volumes and distending pressures the chest wall contributes significantly to changes in respiratory system elastance.