Types Of Vascular Lesions Research Articles

FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and plays an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. We and others have recently shown that FXR is also expressed in the vasculature, including endothelial cells and smooth muscle cells (SMC). However, the biological significance of FXR activation in SMC is still poorly understood. In this study, we examine the effect of FXR ligands on the angiotensin system in rat aortic SMC (RASMC), as angiotensin II (Ang II) signalling contributes to various types of vascular lesions by promoting cell growth of vascular SMC. Treatment of RASMC with a FXR ligand showed no obvious effect on the expression of angiotensinogen, Ang II type 1 receptor (AT1R) or type 4 receptor (AT4R) but led to a significant increase in the expression of type 2 receptor (AT2R). FXR ligand treatment also resulted in an inhibition of Ang II-mediated extracellular signal-regulated kinase (ERK) activation and growth proliferation. Promoter reporter gene and electrophoretic mobility-shift assays suggest that FXR upregulates AT2R expression at a transcriptional level. Upregulation of AT2R appears to play a role in the FXR-mediated inhibition of ERK activation via upregulation of Rous sarcoma oncogene (Src) homology domain-containing tyrosine phosphatase 1 (SHP-1) because FXR-mediated upregulation of SHP-1 can be blocked by an AT2R antagonist and FXR-mediated ERK inactivation was significantly attenuated via treatment with either an AT2R antagonist or a SHP-1 inhibitor. FXR in SMC may serve as a novel molecular target for modulating Ang II signalling in the vasculature.

Hippocampal volume is an independent predictor of cognitive performance in CADASIL

Recent evidence suggests that hippocampal changes are present in vascular cognitive impairment but their importance and relationship with ischaemic mechanisms remain controversial. To investigate these issues we performed MRI and cognitive assessment in a large cohort (n=144) of patients with CADASIL, a hereditary small vessel disease and model of pure vascular cognitive impairment. Dementia status was ascribed according to DSM-IV and global cognitive function assessed with the Minimental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Hippocampal volume (HV) correlated with age (r=−0.33, p<0.001), brain volume (r=0.39, p<0.001) and lacunar lesion volume (r=−0.23, p=0.008), but not white matter lesions or microhaemorrhages. HV was reduced in dementia (2272±333mm3 versus 2642±349mm3, p<0.001) in the whole cohort and the subgroup progressing to dementia before age 60. HV correlated with MMSE (r=0.30, p<0.001), MDRS (r=0.40, p<0.001) and in a multivariate model predicted cognition independent of typical vascular lesions and whole brain atrophy. These findings strengthen the view that hippocampal atrophy is an important pathway of cognitive impairment in vascular as well as degenerative disease.

Expression of the leptin receptor in different types of vascular lesions

Clinical and experimental evidence suggests that the adipokine leptin may be important for the development of cardiovascular complications associated with obesity, possibly through interaction with its receptor on vascular cells. In the present study, we systematically analysed expression of the leptin receptor in normal and diseased vascular specimens using immunohistochemistry, immunofluorescence and quantitative real time-PCR. In particular, human atherosclerotic plaques as well as experimental vascular lesions induced in hypercholesterolemic mice and minipigs, respectively, were examined. Our results demonstrate the presence of the leptin receptor in normal vessel wall segments as well as neointimal or atherosclerotic lesions. In the latter, ObR expressing cells were predominantly localised on the luminal border and within the subintima, and coexpression of von Willebrand factor, VEGF receptor-2 or VE cadherin identified them as endothelial cells. Moreover, CD14-positive monocytes/macrophages were strongly positive for the leptin receptor. In contrast, only few ObR-expressing smooth muscle cells could be detected in human atherosclerotic plaques. The findings of the present study thus support a possible action of leptin on the cardiovascular system by demonstrating expression of the leptin receptor in different types of vascular lesions.

Sorting out the clinical consequences of ischemic lesions in brain aging: A clinicopathological approach

Background Vascular lesions are particularly common in the aged brain. However, it is still unclear whether all such lesions affect cognition. Objectives To better explore relationships between specific characteristics of vascular lesions (type, size and location) and cognitive status. Methods We performed a review of currently available neuroimaging and post-mortem studies taking into account several recent clinicopathological reports in elderly individuals with varying levels of cognitive impairment. Results New data reveals the significant impact of cortical microinfarcts on intellectual function, in contrast to focal cortical and white matter gliosis which are not significantly associated with cognitive status. Structural neuroimaging studies show inconsistent data regarding the cognitive consequences of WML. Neuropathological analyses reveal that both periventricular and subcortical demyelination are associated with cognitive status in the absence of macrovascular pathology. When lacunes are present, these microvascular lesions have no independent effect on intellectual impairment. The relationship between lacunes and cognition is highly dependent on localization. Basal ganglia and thalamic lacunes correlate with cognitive decline but not lacunes in the frontal, temporal and parietal deep white matter. Conclusion Recent studies suggest that some cases of dementia might be misclassified: 1. Cases with typical Alzheimer course and moderate lacunes in subcortical white matter should probably be considered pure Alzheimer's disease. 2. The presence of microscopic infarcts can markedly impact cognition but is not detectable by currently available neuroimaging techniques and the vascular component of such mixed cases may go undiagnosed. The development of urgently needed new criteria for vascular dementia should take into account the relative contribution of various types of vascular lesions that can impact cognitive function.

Transglutaminase-dependent RhoA Activation and Depletion by Serotonin in Vascular Smooth Muscle Cells

The small G protein RhoA plays a major role in several vascular processes and cardiovascular disorders. Here we analyze the mechanisms of RhoA regulation by serotonin (5-HT) in arterial smooth muscle. 5-HT (0.1-10 microM) induced activation of RhoA followed by RhoA depletion at 24-72 h. Inhibition of 5-HT1 receptors reduced the early phase of RhoA activation but had no effect on 5-HT-induced delayed RhoA activation and depletion, which were suppressed by the 5-HT transporter inhibitor fluoxetine and the transglutaminase inhibitor monodansylcadaverin and in type 2 transglutaminase-deficient smooth muscle cells. Coimmunoprecipitations demonstrated that 5-HT associated with RhoA both in vitro and in vivo. This association was calcium-dependent and inhibited by fluoxetine and monodansylcadaverin. 5-HT promotes the association of RhoA with the E3 ubiquitin ligase Smurf1, and 5-HT-induced RhoA depletion was inhibited by the proteasome inhibitor MG132 and the RhoA inhibitor Tat-C3. Simvastatin, the Rho kinase inhibitor Y-27632, small interfering RNA-mediated RhoA gene silencing, and long-term 5-HT stimulation induced Akt activation. In contrast, inhibition of 5-HT-mediated RhoA degradation by MG132 prevented 5-HT-induced Akt activation. Long-term 5-HT stimulation also led to the inhibition of the RhoA/Rho kinase component of arterial contraction. Our data provide evidence that 5-HT, internalized through the 5-HT transporter, is transamidated to RhoA by transglutaminase. Transamidation of RhoA leads to RhoA activation and enhanced proteasomal degradation, which in turn is responsible for Akt activation and contraction inhibition. The observation of transamidation of 5-HT to RhoA in pulmonary artery of hypoxic rats suggests that this process could participate in pulmonary artery remodeling and hypertension.

1992: Parodi, Montefiore, and the First Abdominal Aortic Aneurysm Stent Graft in the United States

In 1990 Juan C. Parodi performed the first endovascular abdominal aortic aneurysm (AAA) repair in Buenos Aires. Two years later, in 1992, Parodi and Claudio Schonholz visited Montefiore Medical Center in New York to perform with us the first endovascular AAA repair to be done in the United States. Since then the Montefiore/Einstein vascular group has performed 1522 endovascular grafts in 674 patients for many types of vascular lesions using a variety of both surgeon-made and industry-made devices. The purpose of the present article is to describe the events that surrounded the performance of the first seminal endovascular AAA repair at our institution on November 23, 1992.

Three-Dimensional Power Doppler Sonography in the Diagnosis of Arteriovenous Malformation of the Uterus

Arteriovenous malformations (AVMS) are uncommon vascular lesions that may arise in the myometrial layer of the uterus, causing menometrorrhagia. 1 - 3 As reported previously, they are amenable to sonographic detection, 4 - 8 although Doppler ultrasound examinations are not always able to distinguish true AVMs from other types of vascular lesions of the uterus. X-ray angiography is commonly required to confirm the diagnosis and to establish the appropriate treatment.7-9 In this case, 3-dimensional (3D) power Doppler sonography was valuable in diagnosing a true AVM of the uterus.

Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis

To evaluate the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Behçet's disease (BD). Included were 118 consecutive Italian BD patients followed over a 3-year period (1997-1999) who satisfied the International Study Group criteria for BD. The control group consisted of 132 healthy Italian blood donors. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific restriction enzyme techniques for factor V Leiden and prothrombin gene G20210A polymorphisms. Vascular lesions were observed in 37 (31.4%) patients. The 2 most common lesions were subcutaneous thrombophlebitis (10.2%) and deep vein thrombosis (DVT) of the legs (22.8%). No significant demographic and clinical differences between patients with and without DVT were present. The distribution of allele and genotype frequencies of prothrombin gene G20210A and factor V Leiden polymorphisms did not differ significantly between BD patients and healthy controls. The frequencies of carriage rates of prothrombin gene G20210A and factor V Leiden polymorphisms in BD patients with and without DVT were similar. However, the frequency of 20210A allele was significantly higher in BD patients with ocular disease than in those without, particularly in the patients with posterior uveitis/retinal vasculitis. The frequency and types of vascular lesions in Italian BD patients were similar to those reported in studies from other countries. No association between factor V Leiden mutation and G20210A mutation in the 3'-untranslated region of the prothrombin gene with DVT was found. However, a prothrombin gene G20210A mutation may influence the development and severity of ocular involvement in BD.

Treatment of the vascular lesions of the face and neck using selective vascular photothermolysis with intense pulse light

Intense pulse light with a flash lamp has been a treatment modality for several years. The technology uses multiple filters capable of treating various types of vascular lesions. An advantage of this diverse machine is the ability to adjust wavelengths through different filters and modify pulse duration and pulse delay. This allows treatment of various vascular lesions of different size and depth. This retrospective study in 44 patients determined the long-term outcomes and efficacy of intense pulse light on vascular lesions of the face, including telangiectasias, rosacea, cavernous hemangioma, and port wine stains. We also evaluated the proportional clearance of the lesion, number of treatments to achieve optimal results, side effects, and patient satisfaction. Patients were followed for an average of 19 months and received an average of 2.9 treatments. In 52% of patients there was over 75% resolution of the lesions. A higher number of treatments resulted in better outcomes without any increase in the side effects. Overall 81% of the patients were totally satisfied with the treatment. Intense pulse light offers an easy and effective way of treating vascular lesions of the face and neck. It has minimal side effects and yields high patient satisfaction.

Chronic rejection with or without transplant vasculopathy.

Chronic allograft nephropathy (CAN) is defined and graded in the Banff '97 scheme by the severity of interstitial fibrosis and tubular atrophy. It has been denoted that chronic rejection can be diagnosed if the typical vascular lesions are seen, consisting of fibrointimal thickening. We observed several patients who developed CAN without vascular changes or signs of cyclosporine toxicity. Therefore, we assessed the risk factor profiles of CAN with and without transplant vasculopathy. A cohort of 654 cadaveric renal transplants performed between 1983 and 1997 that functioned for more than 6 months was studied. Fifty-four transplants had CAN defined by a significant decline in renal function together with interstitial fibrosis and tubular atrophy without signs of cyclosporine nephrotoxicity or recurrent disease. Using the Banff chronic vascular (CV) score, 23 of 54 cases (43%) had a chronic vasculopathy score of 0 or 1 whereas 31 cases (57%) had a CV score of 2 or 3. Applying multivariate logistic regression, predictor variables of the two groups were compared with 231 transplants with a stable function for at least 5 yr. Graft histology was obtained at a mean of 2.4 and 2.9 yr after transplantation in the group with or without vasculopathy, respectively. Acute rejection episodes (AREs) after 3 months post-transplantation were the strongest risk factor for both forms of CAN, odds ratio (OR) 14.7 (6.0-36.0). CAN with vasculopathy was also associated with transplants performed in the 1980s, OR 4.95 (1.65-14.9) and with creatinine clearance at 6 months, OR 0.58 (0.44-0.75) per 10 mL/min increase. In contrast, young recipient age, OR 0.69 (0.47-0.99) per 10-yr increase, and the presence of panel reactive antibodies at the time of transplantation, OR 1.26 (1.08-1.47) per 10% increase, were independent risk factors for CAN without vasculopathy. After exclusion of cyclosporine toxicity or recurrent disease CAN occurred without moderate or severe transplant vasculopathy in 43% of the cases. The correlation with young recipient age, sensitization and late ARE suggest an immune pathogenesis, consistent with chronic rejection.

Development of a CT-based weighted rating scale for subcortical cerebrovascular disease sensitive to mild clinical symptoms

Objective: To devise and validate a CT-based visual rating scale sensitive to subcortical cerebrovascular disease (sCVD) in patients with cognitive impairment. Methods: Three types of vascular lesions were rated separately in 16 brain regions. A unique vascular score was computed weighing the regression coefficients of the three scores in linear models. Thereafter, subcortical vascular classes (SVC) of increasing severity (0–3) were created. Known-group and convergent validity of the SVC was tested in 122 cognitively impaired patients with MMSE of 18 and higher. These patients were grouped according to clinical diagnosis in degenerative, mixed, and vascular. Results: Intraclass correlation coefficients were between 0.86 and 0.94. The subcortical vascular score was 8.0±9.4 in the degenerative, 33.0±17.2 in the mixed, and 36.8±14.8 in the vascular patients ( p=0.0001). In particular, none of the degenerative patients had SVC=3, and only 14% had SVC=2. On the contrary, none of the mixed and vascular patients had SVC=0, while about 50% had SVC=3 in both groups. The prevalence of hypertension was increasing with increasing SVC ( p for trend=0.02). The performance on tasks evaluating balance, gait, and bradykinesia decreased with increasing SVC severity ( p for trend=0.006, 0.01, 0.001, respectively). Conclusion: The scale is a valid tool to estimate the vascular component in patients with cognitive impairment.

TNFα induces expression of transcription factors c-fos, Egr-1, and Ets-1 in vascular lesions through extracellular signal-regulated kinases 1/2

Migration, proliferation and differentiation of vascular smooth muscle cells (VSMC) and macrophages are important pathological responses that contribute to the development and progression of vascular lesions. Cytokines such as TNFα are present at sites of vascular injury and regulate a variety of cellular functions of inflammatory cells and VSMC. Cell migration, proliferation and differentiation require de novo gene transcription resulting from extracellular signals being transduced to the nucleus, where multiple genes are regulated to participate in lesion formation. In VSMC and macrophages, TNFα induces activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2), which transmit signals from the cytosol to the nucleus. Potential nuclear targets of TNFα-activated ERK 1/2 include the transcription factors Ets-1, Egr-1, and c-fos, which are known to regulate cellular growth, differentiation, and migration. The aim of this study was to investigate the expression of the transcription factors Ets-1, Egr-1 and c-fos in different types of vascular lesions, their regulation by TNFα and the role of ERK 1/2 in these signaling events. Atherosclerotic lesions from fructose-fed LDL-receptor deficient mice and neointimal lesions from rat aortae 2 weeks post balloon injury demonstrated the presence and colocalization of TNFα, phosphorylated and activated ERK 1/2, and transcription factors Ets-1, Egr-1 and c-fos. Neointimal lesions consisted primarily of VSMC, whereas atherosclerotic lesions predominantly contained macrophages. In cultured rat aortic VSMC, TNFα (100 U/ml) stimulated a rapid and transient expression of Ets-1, Egr-1 and c-fos with a maximal induction 1 h after stimulation. In cultured RAW 264.7 mouse macrophages, TNFα similarly induced the expression of Ets-1, Egr-1, and c-fos. Induction of these transcription factors was mediated via ERK 1/2 activation, since the ERK 1/2-pathway inhibitor PD98059 (10–30 μM) significantly inhibited their TNFα-induced expression. TNFα induced ERK 1/2 activation in both cell types. These findings underscore the importance of the ERK 1/2 pathway in the expression of TNFα-regulated transcription factors, which may participate in different forms of vascular lesion formation.

Human blood platelet gC1qR/p33.

Platelets are involved in the development of many types of vascular lesions. In addition to their role in primary hemostasis, they participate in inflammatory processes that may contribute to the development of thrombosis, atherosclerosis and vasculitis. In this regard, we have been interested in platelet interactions with the complement subcomponent C1q. C1q has been shown to modulate platelet interactions with collagen and immune complexes, and has been identified at sites of vascular injury and inflammation, as well as in atherosclerotic lesions. Platelets express a variety of C1q binding sites, including gC1qR/p33 (gC1qR), a multifunctional, multicompartment cellular protein. Here we focus on the structure and function of platelet gC1qR and its emerging role in modulating platelet function at sites of vascular injury and inflammation.

Renovascular disease and hypertension in children with neurofibromatosis.

Neurofibromatosis type 1 (NF1) is associated with vascular lesions, such as renal artery stenosis, and secondary hypertension. The real prevalence is largely unknown, particularly in children. We observed 27 patients with NF1, mean age 12.8 years (range 4.2-24 years), for 2-10 years to assess the association of NF1 with vascular abnormalities and secondary hypertension. Patients were studied with angiography, 24-h blood pressure monitoring, a captopril test, and Doppler ultrasonography of aorta and renal arteries. The prevalence of hypertension was 18.5%; 61.5% of patients studied with angiography had vascular lesions, half of whom were apparently normotensive. However, they had abnormal 24-h blood pressure monitoring, which was a first sign of poor blood pressure control. Those patients with severe hypertension (11.1%) were successfully treated with percutaneous transluminal angioplasty (PTA); stenosis recurred in 2 of 3 patients after a 2-year follow-up period, and was responsive to drugs. We conclude that hypertension is a frequent complication of NF1 in pediatric patients, it is usually secondary to typical vascular lesions, and requires careful follow-up. Ambulatory blood pressure monitoring (24-h) is a sensitive method for detecting initial alterations of the blood pressure pattern. PTA may be an effective treatment in this condition.

Spontaneous improvement in reduced vasodilatory capacity in major cerebral arterial occlusive disease.

Reduced vasodilatory capacity resulting from occlusive lesions of the major cerebral arteries may return to normal without surgical revascularisation. We aimed to determine prospectively the frequency and predictors of recovery of impaired haemodynamics as demonstrated by acetazolamide (ACZ) reactivity on single-photon emission computed tomography (SPECT). Vasoreactivity was measured by (123)I-IMP SPECT with an ACZ challenge, in 37 medically treated patients with unilateral occlusive disease of the internal carotid or middle cerebral artery at an interval of 1-2 years. Each ACZ challenge test was analysed semiquantitatively by calculating the degree of increase in cerebral blood flow (CBF) asymmetry after ACZ administration (DeltaAI). Vasodilatory capacity was abnormal initially in 20 patients (65 %); eight of whom (40 %) exhibited spontaneous normalisation on follow-up. Although the baseline characteristics did not differ significantly between patients with or without increase in reactivity, logistic regression analysis revealed that the initial DeltaAI (P < 0.05) and the type of vascular lesion (stenosis or occlusion) (P < 0.05) correlated significantly with a return towards normal of reduced ACZ reactivity. Spontaneous improvement of impaired vasodilatory capacity may not be a rare phenomenon. We found that mild reduction in the initial ACZ reactivity and a stenosis, but not complete occlusion, were independent factors contributing to normalisation of impaired cerebral haemodynamics.

Acute vascular rejection: a clinical and morphological study.

We analyzed one special type of acute vascular rejection (AVR), defined as fibrous thickening of the arterial intimal layer that leads to early renal failure. Twenty-one patients who presented this histological pattern were studied among 339 transplanted over 4 years. Patients were separated into two groups. Thirteen patients have restained their kidneys (Group A, 61.9%) and 8 have lost their grafts (Group B, 38%). Diagnosis was made on average 430. POD in GA and at 49 degrees POD in GB on the 43rd postoperative day in group A and on the 49th postoperative day in group B (NS). In group A, mean serum creatinine is 2.2 mg/dl and follow-up time is 29 months. Oliguria was much more frequent in group B (75% versus 15.3%, P = 0.01). These patients were submitted to 91 renal biopsies always because of non-function. Typical vascular lesions began at arcuate arteries and progressed, as seen in sequential biopsies, to interlobular arteries and arterioles. When only arcuate arteries were affected, 22.5% of renal losses were seen, but when arcuate plus interlobular arteries were compromised, 72.2% of patients lost their kidneys (P = 0.006). We did not identify any difference in immunofluorescent staining from biopsies with or without vascular rejection, or between groups A and B. We concluded that about 2.3% of our patients lost their kidneys because of this kind of AVR, diagnosed near the 43rd postoperative day. The only clinical predictive sign of poor reversibility was oliguria. The attack on arcuate plus interlobular arteries meant a poor prognosis. Immunofluorescent staining did not have a prognostic value.

Acute vascular rejection: a clinical and morphological study

Abstract We analyzed one special type of acute vascular rejection (AVR), defined as fibrous thickening of the arterial intimal layer that leads to early renal failure. Twenty-one patients who presented this histological pattern were studied among 339 transplanted over 4 years. Patients were separated into two groups. Thirteen patients have restained their kidneys (Group A, 61.9 %) and 8 have lost their grafts (Group B, 38 %). Diagnosis was made on average 430. POD in GA and at 49° POD in GB on the 43rd postoperative day in group A and on the 49th postoperative day in group B (NS). In group A, mean serum creatinine is 2.2 mg/dl and follow-up time is 29 months. Oliguria was much more frequent in group B (75% versus 15.3%, P= 0.01). These patients were submitted to 91 renal biopsies always because of non-function. Typical vascular lesions began at arcuate arteries and progressed, as seen in sequential biopsies, to interlobular arteries and arterioles. When only arcuate arteries were affected, 22.5 % of renal losses were seen, but when arcuate plus interlobular arteries were compromised, 72.2 % of patients lost their kidneys (P= 0.006). We did not identify any difference in immunofluorescent staining from biopsies with or without vascular rejection, or between groups A and B. We concluded that about 2.3 % of our patients lost their kidneys because of this kind of AVR, diagnosed near the 43rd postoperative day. The only clinical predictive sign of poor reversibility was oliguria. The attack on arcuate plus interlobular arteries meant a poor prognosis. Immunofluorescent staining did not have a prognostic value.

Radiation-induced bile duct injury: a vanishing cause of obstructive jaundice?

Although radiotherapy has been recognized for decades as a potential source of injury of various parts of the gastrointestinal tract, it remains a rare cause of bile duct stricture. The paper by Cherqui et al. (1), which appears in another section of this issue, illustrates two additional cases of bile duct stricture occurring in the long term after upper abdominal radiation therapy for lymphoma. Characteristics of these cases include the occurrence of symptoms of bililary obstruction after a 10-year symptom-free period and also the importance of echoendoscopy for diagnosis. The fact that bile duct injury became symptomatic after as long as 10 years remains somewhat unusual, since experiments performed in dogs with intraoperative irradiation have shown that complications began to manitest as early as 6 weeks after the procedure. However, in this model, the time elapsed between treatment and symptoms was clearly dose dependent. Animals receiving 4500 fads became jaundiced after 6 weeks, while those treated with 2000 rads remained asymptomatic for up to 8 months (2). In humans, doses in the range of 4000-5000 rads were found responsible for symptomatic biliary stricture after 8 to 30 months (3). Whether such damage is facilitated by previous or concomitant chemotherapy is not well known. In the reported cases symptoms occurred after 10 years, but whether they were preceded by asymptomatic biochemical cholestasis is not known. The pathogenesis of irradiation injury to tubular viscera is not well known. However, common features of those lesions include progressive obliterative vasculitis, various degrees of epithelial atrophy and/or ulcerative changes and fibrosis (2~,). The fact that ischemia plays a major role in the pathogenesis of the lesions is supported by the higher incidence of gastrointestinal irradiation injury in patients with decreased cardiac output, hypertension, diabetes and arteriosclerosis (4). This pathogenetic mechanism also explains why in general, lesions are more prone to develop in regions with reduced arterial supply such as those located in terminal vascular beds. When the common bile duct is involved, the region of reduced vascular supply is located between the territories of the cystic vessels which originate from the right hepatic artery and those vascularized by the pancreatico-duodenal arcade. It is thus not surprising that in some cases, the middle segment of the bile duct exhibits more severe damage than the other parts of the biliary tree. This is, however, likely to be influenced by the wide interindividual variability in vascular mapping. From a pathological point of view, reported cases of bile-duct-induced irradiation injury showed vascular changes including intimal arteriolar thickening responsible for lumen narrowing and also dense inflammatory fibrosis replacing the muscular layer and inducing variable degrees of stenosis. Vascular changes are a well-known effect of irradiation and have been extensively studied in the therapy of different types of vascular lesions. They mainly affect small caliber venous or arterial vessels and generally spare large vascular channels such as the aorta, the portal vein and the vena cava. In contrast, in small venous branches such as the hepatic sinusoids and hepatic venules, irradiation may be responsible for endothelitis and thrombosis which may eventually lead to veno-occlusive disease (5,6). The pathogenesis of arteriolar intimal thickening in radiation injury is not well known but probably plays a significant role in ischemia and also in the pathogenesis of epithelial

Cerebral Infarcts and Seizures in the Neonate

A retrospective analysis was performed on 54 infants who suffered perinatal hypoxic-ischemic insults and came to autopsy, in an attempt to assess the association of cerebral infarcts with seizures. Fifty infants had several types of cerebrovascular lesions, including intraventricular hemorrhage (32 cases), periventricular leukomalacia (24), ischemic neuronal necrosis (18), pontosubicular necrosis (12), cerebral infarct (9), and cerebellar hemorrhage (7). Of these infants, nine had electroencephalographic seizures. Among a variety of cerebrovascular lesions, cerebral infarcts represented the single lesion most highly correlated with seizures. The incidence of seizures in infants with cerebral infarcts (44%) was significantly higher than with other types of vascular lesions.

Anatomic study of a particular type of vascular lesion associated with tibial fractures.

Proximal tibiofibular dislocations are rare lesions, especially as they may pass unnoticed when associated with tibial fractures. Anatomically, there is bony and ligamentous predisposition to upward and backward dislocation of the proximal tibiofibular joint which is promoted by the shortening of the lower limb accompanying a tibial fracture. We report 3 tibial fractures associated with acute ischemia due to proximal tibiofibular dislocation, an association never previously described. This lesion and its mechanism were studied anatomically.