A comparative in vitro evaluation of different therapeutic protocols for vascular graft infections.
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Biomedical subjects
Publications and source records attributed to P Fiorani.
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Radiolabelled autologous low density lipoprotein (LDL) has previously been used to study in vivo distribution and metabolism of native-LDL. Non-invasive imaging of atherosclerotic lesions using 99mTc-LDL was shown to be feasible in animal models and patients but the clinical utility remains to be assessed. Since recent reports suggest that oxidized LDL may play a major role in the pathogenesis of atherosclerosis, we developed a technique to oxidize autologous LDL and compared the biodistribution of oxidized-LDL with that of native-LDL in man. In addition, we evaluated the uptake in vivo of oxidized- and native-LDL by atherosclerotic plaques. LDL, obtained from human plasma was treated with various combinations of copper ions and H2O2 to induce oxidative modification by increasing the content of lipid peroxidation products and electrophoretic mobility. When LDL (0.3 mg/ml) was incubated with 100 microM Cu2+ and 500 microM H2O2 oxidation occurred rapidly within 1 h, and was labelled with 99mTc efficiently as native LDL. In vivo distribution studies revealed a faster plasma clearance of oxidized-LDL compared to native-LDL, and a higher uptake by the reticuloendothelial system. Tomographic scintigraphy of the neck in patients suffering from transient ischemic attacks, revealed accumulation of radiolabelled LDL preparations in the carotid artery affected by atherosclerotic lesions. We developed a technique to rapidly oxidize LDL using copper and H2O2. Biodistribution data demonstrate that oxidized-LDL is rapidly cleared from circulation, is taken up mostly by organs rich in macrophages, and can be detected at the level of carotid plaques.
OBJECTIVES: Studies comparing transcranial Doppler ultrasonography (TCD) with other intraoperative monitoring techniques for detecting clamping ischaemia during carotid endarterectomy under general anaesthesia suggest that a reduction of > two-thirds in the mean middle cerebral artery velocity (mMCAv) or a reduction of > 0.4 in the preclamping mMCAv: clamping mMCAv ratio warrants cerebral protection. Our aim was to study the relationship between mMCAvs and clamping ischaemia during carotid endarterectomy in awake patients. MATERIALS AND METHODS: In a consecutive series of 57 patients undergoing carotid endarterectomy under locoregional anaesthesia 51 were monitored by intraoperative TCD, continuous EEG, and neurologic awake testing. RESULTS: Five of the 51 (9.8%) patients had transient clamping ischaemia, which carotid shunting reversed. TCD showed that these five patients had significant lower mean mMCAvs than the other 46 patients, who had no deficits (1.8 +/- 1.1 cm/s vs. 26.2 +/- 8.5, p = 0.0003). Current TCD criteria indicated that four other patients (7.8%) should have been shunted. All four had significantly higher clamping mMCAvs than the five shunted patients (11.5 +/- 1.9 vs. 1.8 +/- 1.1, p = 0.0012). CONCLUSIONS: Intraoperative TCD detected cerebral ischaemia and yielded no false-negative. An mMCAv of 10 cm/s or less may indicate the risk of clamping ischaemia better than the higher threshold currently proposed. This would avoid unnecessary shunting due to false-positives.
Secondary aorto-enteric fistula is one of the most serious complications of abdominal aortic reconstruction. Conventional management includes removal of all infected prosthetic graft, oversewing of aortic stump and restoration of lower limbs blood flow by extraanatomic bypass grafting, reporting high rates of mortality, limb loss, and even infection of the extraanatomic grafts. Dissatisfied by these results, frequently, due to aortic stump blowout or extraanatomic by-pass reinfection, some authors attempted a more conservative approach with au in situ replacement by a new synthetic graft. The aim of this paper was to verify the role of in situ graft replacement. From December 1989, 8 patients with secondary aorto-enteric fistula underwent in situ PTFE graft replacement. One patient (12.5%) died perioperatively for acute myocardial infarction. No limb loss occurred. One patient died after 44 months from pulmonary neoplasia without signs of graft infection. The others are doing well at 34 months follow-up. The authors suggest that, in selected patients, in situ prosthetic graft replacement provides better early and late results than extranatomic bypass.
Early restenosis represent the most important and more common failure after carotid endarterectomy. For this reason, after its first description made in 1976 by Stoney and String, it raised general interest among vascular surgeons. In spite of the efforts to clear the causes of this phenomenon, none of the numerous papers published in the literature has defined a specific cause determining restenosis. Nevertheless, at present, this hyperplastic response of the arterial wall to trauma after operation is generally considered benign because it is rarely responsible for new neurological symptoms or early internal carotid artery occlusion. This unanimous conviction has been achieved after years of instrumental and clinical postoperative follow-up performed all over the world. At the same time and probably for these reasons, recently, a new discussion has begun about the usefulness and cost-effectiveness of prolonged Duplex scanning postoperative surveillance of the endarterectomized carotid arteries. This new question raised our curiosity in verifying the validity of this new approach, so we reviewed accurately our laboratory follow-up registry and the data regarding onset, evolution and clinical outcome of early restenosis. These data associated with a meticulous review of the experience of other authors convinced us that the patients operated on, need, in most cases, a short even aggressive period of careful follow-up (generally the first six months).(ABSTRACT TRUNCATED AT 250 WORDS)
In patients with aortoiliac disease and a stenosis of one or two renal artery, renal hypertension is rarely the sole mechanism of the elevated blood pressure. The preservation of nephron mass being the aim of the renal revascularization, we firmly believe that only three tests are required for the operative decision: renal ultrasonography, nephroscintigraphy and global and selective aortography.
A full-length human DNA topoisomerase I complementary DNA clone was mutagenized in vitro and the mutagenized DNA was used to replace wild-type human TOP1 complementary DNA in YCpGAL1-hTOP1, a plasmid constructed for the expression of the human enzyme in yeast. A yeast strain devoid of yeast DNA topoisomerase I and permeable to the anticancer drug camptothecin was transformed with the plasmid pool. Assays of DNA topoisomerase I in lysates of camptothecin-resistant transformants identified one with nearly the same level of the enzyme as transformants of unmutagenized YCpGAL1-hTOP1, and a single mutation changing Gly363 to a cysteine was found in this mutant. The G363C mutant enzyme was overexpressed in yeast and partially purified. It differed significantly from wild-type human DNA topoisomerase I similarly expressed and purified: camptothecin-stimulated cleavage of DNA was observed with the wild-type but not the G363C enzyme, and the DNA relaxation activity of the mutant enzyme, unlike that of the wild-type enzyme, was not significantly stimulated by Mg(II). The positions of the G363C and other previously reported camptothecin resistance mutations in eukaryotic DNA topoisomerase I were discussed in terms of a model in which the active site is an interdomainal cleft.
A 5-year experience of 19 aortic graft infections is reviewed. Of these, 13 (68%) had a late onset (more than 4 months after graft implantation) and usually presented with anastomotic pseudo-aneurysm or thrombosis. The remaining six infections (32%) had an early onset and presented more often with surgical wound infection. Aorto-enteric fistulae and inguinal sinus tracts were observed in both early and late onset infections. Coagulase-negative staphylococci (all slime negative, oxacillin susceptible strains) were the prevalent pathogens in both groups of infections and were isolated in six (32%) patients. Next most commonly seen were Pseudomonas aeruginosa in four (21%) patients, Enterococcus spp. in three (16%) patients, Staphylococcus aureus in three (16%) patients, other bacteria in six (32%) patients. No organisms were isolated in three (16%) patients. Mortality and major amputation rates were 47.3% and 31.6%, respectively. The therapeutic procedures included total graft removal (15 patients), partial graft excision (two patients), partial graft excision followed by total graft removal (one patient) and local treatment without graft removal (one patient). Six patients recovered, including two who underwent total graft removal associated with a non-conventional 'in situ' graft replacement and one patient treated conservatively with local treatment and antibiotics. The three patients undergoing partial graft excision showed signs of active infection of the residual graft.
Patients at risk of hyperperfusion syndrome after carotid endarterectomy are often severely hypertensive and have a high grade internal carotid artery stenosis with disordered autoregulation due to a loss of reserve capacity (RC). Cerebral RC can be studied by sophisticated and expensive technical devices (SPECT, PET). Recently it has been demonstrated that the transcranial Doppler (TCD) and acetazolamide provocation test can be used to assess RC. From September 1991 to January 1992, 36 patients were studied by the TCD and acetazolamide test prior to carotid endarterectomy to identify patients at high risk of the hyperperfusion syndrome. Preoperatively, the patients were studied by TCD at rest and after vasolidation with acetazolamide 1 g intravenously (i.v.). Mean blood flow velocity on the middle cerebral artery (MCAv) was recorded for the following 20 min at 5 min intervals. MCAv at rest was 49 +/- 17 cm/s. After acetzaolamide infusion in 33 patients (92%), the mean MCAv was 62 +/- 19 cm/s with an increase of 19 +/- 13 cm/s (normal RC). In three patients (8%), the mean MCAv was 43 +/- 22 cm/s with a decrease of -6 +/- 3 cm/s with respect to base values (reduction of RC). (t = 3.30; p = 0.0022). All these patients were hypertensive (BP > 180/100 mmHg) and had a carotid artery stenosis > 90%. Postoperatively, the three patients with reduction of RC complained of homolateral headache. TCD showed a mean MCAv of 67 +/- 17 cm/s, an increase compared to the preoperative rest values of 17 +/- 8 cm/s, the 33 patients with normal RC showed a mean change in MCAv -2 +/- 12 cm/s.(ABSTRACT TRUNCATED AT 250 WORDS)
Patients with severe bilateral carotid lesions (stenosis and contralateral internal carotid occlusion) are at high risk of having a stroke, and carotid endarterectomy has been proposed as the best treatment. In spite of improvements in surgical technique, this operation is still associated with significant perioperative complications (5-13%) which are frequently (up to 40%) correlated with intolerance to internal carotid artery clamping. For this reason, intraoperative cerebral monitoring able to accurately detect ischaemia during surgery would be useful. Reviewing our experience from the last 7 years in 74 patients operated on for stenosis and contralateral occlusion of the internal carotid artery, we found a 1.3% neurological morbidity and 1.3% mortality rate. Presenting symptoms included focal transient ischaemia attacks (TIAs) in 57 patients, stroke in 16 patients and two patients were asymptomatic. Half of these patients (37) were operated on under general anaesthesia with electroencephalogram (EEG) monitoring, stump pressure measurement and selective shunting. In this group, two patients (5.4%) sustained a postoperative stroke, one of which was fatal. The remaining 37 patients were operated on under local-regional anaesthesia with selective shunting on the basis of neurological deficit onset or loss of consciousness during the test clamp. There were no postoperative neurological complications in this group but one patient died of acute myocardial infarction on the 6th postoperative day. This experience suggests that it is possible to perform carotid endarterectomy in patients with severe bilateral lesions with a postoperative complication rate similar to that in patients with less complicated obstructive lesions if accurate intraoperative cerebral monitoring is used.
In the early treatment of the patients with cerebrovascular insufficiency due to internal carotid artery stenosis, the presence of a cerebral infarct and especially the blood brain barrier breaking (BBB) are considered by many as a contraindication to early reperfusion by carotid endarterectomy (CEA). Generally, it has been recommended to differ the operation at least for 4-6 weeks because of the high risk to convert an ischemic infarct into an hemorrhagic one. On the other hand, because unfavorable natural history has been reported as for the progressing unstable neurological deficit as for the minor recent strokes, respectively by Millikan and Dosik, it seem to be justified a more aggressive management with the aim of: 1) eliminating the stenosis as embolic source of emboli; 2) obtaining early brain reperfusion to increase the probability of good recovery. Some previous experiences reported in the literature demonstrated satisfactory results of early reperfusion even in presence of BBB. The Authors present 4 cases of early CEA in patients with BBB. After the CT scan the patients have been submitted preoperatively to non invasive tests (duplex scanning and transcranial Doppler sonography) to assess the presence of the internal carotid artery stenosis and the viability of the intracranial cerebral arteries with special regard to the middle cerebral artery. All the patients underwent CEA in loco-regional anesthesia and particularly systemic blood pressure was carefully monitored and any hypertensive status was early corrected by prompt antihypertensive therapy (i.v. nitrates and or calcium blocking agents).(ABSTRACT TRUNCATED AT 250 WORDS)
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PURPOSE: To reduce the rates of morbidity and mortality in aortic graft infection, a new diagnostic approach is needed to help identify low-grade stages, specifically when there are minimal or no clinical signs of overt infection. The aim of this study was to evaluate the role of technetium 99m--hexametazime white blood cell scanning (99mTc scanning) in detecting aortic graft infection, particularly in the low-grade stages. METHODS AND RESULTS: Thirty-seven patients with suspected aortic graft infection were categorized into three groups according to their signs and symptoms on readmission. Ten patients (group A) had advanced graft infections that were correctly diagnosed by use of computed tomography (CT) scanning and 99mTc scanning and confirmed by intraoperative findings and culture results. Eighteen patients (group B) had nonspecific signs and symptoms of graft infection. Patients only underwent CT and 99mTc scanning for graft infection after standard clinical work-ups failed to reveal disease processes that accounted for the clinical symptoms. In this group of patients 99mTc scanning identified four cases of low-grade graft infection, which was confirmed by intraoperative findings and graft cultures. None of these four cases was confirmed by results of CT scanning. On an average 18-month follow-up in patients who did not undergo surgery graft infections developed. Nine patients (group C) had anastomotic aneurysms; CT scanning and 99mTc scanning correctly diagnosed five patients as being infected. The result of 99mTc scanning was false-positive in one patient. CONCLUSIONS: The diagnostic accuracy of 99mTc scanning in patients who did not have specific signs of graft infection (groups B and C) was 100% for sensitivity, 94.4% for specificity, 90% for the positive predictive value, and 100% for the negative predictive value. 99mTc scanning seems to be a useful diagnostic technique for detecting aortic graft infection, particularly in low-grade stages.
BACKGROUND: Inflammatory aneurysms of the abdominal aorta constitute an anatomoclinical entity characterised by prominent thickening and fibrosis of the aneurysmal wall, extending to the adjoining structures. Etiology, pathogenesis and relation with atherosclerosis still remain controversial. METHODS: Sixteen consecutive patients undergoing surgery for inflammatory aneurysm of the abdominal aorta between March 1987 and December 1990 were studied (Group I); as a control, a series of 16 consecutive patients operated on in the same period for atherosclerotic aneurysm of the abdominal aorta was selected (Group II). As far as clinical history and symptoms are concerned, the comparison between the two groups revealed significant differences only for hydronephrosis (exclusively present in Group I, p < 0.05) and abdominal pain (more frequent in Group I, p < 0.01). The microscopic study of the aneurysmal wall was performed by scoring its histological features (atherosclerotic lesions, medial and adventitial fibrosis, inflammatory infiltrates and lymphatic stasis) from 1+ to 3+. RESULTS: As regards the microscopical features, atherosclerotic lesions were present in all the examined cases, whereas periadventitial fibrosis appeared in all the aneurysms of Group I and in none of Group II; the comparison between the two groups revealed further significant differences for extensive intimal calcification (exclusively present in Group II, p < 0.05), fibrous replacement of the tunica media (more thorough in Group I, p < 0.02), and the extent of inflammatory infiltrates (more prominent in Group I, p < 0.05). CONCLUSIONS: From the scarcity of pathognomonic features in both case-history and clinical presentation, the constant coexistence of prominent atherosclerotic lesions, and the progressive trend of the pathologic features, inflammatory aneurysms may be inferred to be a variant of atherosclerotic ones, characterised by a particular prominence of inflammation and fibrosis. The frequent occurrence of dilation of both periaortic lymphatic vessels and lymph node sinuses, even in "incipient" aneurysms, supports the hypothesis that it may be the lymphatic stasis which determines periaortic fibrosis. Finally, atherosclerotic components passing into periaortic fibrosis and eliciting granulomatous reaction were observed in two Group I cases featuring prominent "inflammatory" symptoms; such a finding favours the hypothesis that an immune reaction against some components of the atherosclerotic plaque may lead to the pronounced inflammatory response that is peculiar of inflammatory aneurysms.
The authors report their experience from 1985 to 1988 with 75 consecutive patients affected by bilateral carotid artery stenosis in whom only one side was surgically treated and the other had a minor (15-45%) asymptomatic carotid stenosis. These patients have been followed for a period ranging from 10 to 50 months (mean follow-up 21 months) by clinical examinations and non-invasive investigations (Doppler CW, Duplex scanner). The non-invasive evaluation included assessment of haemodynamic data and characterisation of plaque morphology (regular vs. irregular or ulcerated surface, homogeneous vs. heterogeneous plaque). During follow-up eight patients died: two (2.6%) from acute myocardial infarction, four from stroke (5.3%), and two (2.6%) from other causes. Twenty-five patients (33.3%) had neurological symptoms related to the unoperated side: and four suffered stroke (5.3%). Twenty-one patients had TIAs (28%) related to the observed side. During follow-up five out of 29 (17.2%) homogeneous and 20 out of 46 (43.4%) heterogeneous plaques progressed (p less than 0.01). With regard to the surface characteristics, nine out of 25 regular plaques progressed and only three patients (12%) had neurological events; 19 out of 34 (55.9%) irregular plaques showed a progression and 14 caused neurological symptoms. Fourteen ulcerated plaques (87.5%) progressed (p less than 0.01). Our experience suggests that the basic trend in the follow-up of patients with bilateral carotid artery disease, is that the contralateral unoperated lesion may evolve and become symptomatic. These symptoms are generally TIAs but five patients (4.3%) suffered from strokes related to the unoperated side, all without warning TIAs.
Inflammatory abdominal aortic aneurysms are characterized by dense perianeurysmal fibrosis involving the adjacent organs. Attempts to isolate the aneurysm can lead to operative injuries of these structures, thus increasing the rates of complications and mortality. In the last 12 years 45 patients with inflammatory abdominal aortic aneurysms underwent aneurysm resection at the Department of Vascular Surgery of the University of Rome. The aneurysm was resected through a standard, midline transperitoneal approach in 39 patients, through a thoracophrenolaparotomy in two patients, and through a left-flank extraperitoneal approach in the last four patients. The extraperitoneal approach simplified aneurysm dissection and aortic clamping with no cases of postoperative morbidity or death. In addition, we reviewed the CT scan findings of 12 patients surgically treated for inflammatory abdominal aortic aneurysm. The amount of fibrosis in the anterior wall of the aneurysm was greater than in the left posterolateral aspect (p = 0.008). We conclude that the left-flank extraperitoneal approach is the most anatomically advantageous route for repair of inflammatory abdominal aortic aneurysm.
A study was carried out on headache after carotid endarterectomy. A specific type of headache, similar in its characteristics to "cluster headache", occurred on the operative side in 30% of 54 patients, whereas no such headache occurred after extra-intracranial bypass or peripheral vascular surgery. This postoperative headache was not spontaneously reported by 56% of patients unless they were specifically asked about it. Pharmacological pupillary testing performed in 37 patients revealed that a decreased oculosympathetic activity (with or without adrenoceptor supersensitivity) was constantly associated with post-endarterectomy headache. Although this same abnormality was also observed in 54% of the patients without headache, a statistically significant (p less than 0.01) higher prevalence of decreased oculosympathetic responses was found in the patients with headache. The results suggest that damage to the sympathetic plexus due to the surgical procedure is involved in the development of postoperative "cluster-like" headache.