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Background: We are investigating decellularized vein allograft as a scaffold to engineer a non-synthetic, small-diameter vascular graft. This study examines the in vivo behavior of this scaffolding after implantation into the arterial circulation., Materials and Methods: Canine animals underwent bilateral carotid interposition grafting using jugular vein implanted as either: 1) fresh autograft, 2) fresh allograft, or 3) decellularized allograft. Decellularization was achieved using sodium dodecyl sulfate. Grafts were examined with duplex ultrasound biweekly to determine luminal diameter, thrombosis, stenosis, or anastomotic breakdown. After perfusion fixation at 2 or 8 weeks, grafts underwent histological, morphometric, and immunohistochemical examination., Results: All animals survived without neurological or hemorrhagic complication. No deterioration of graft integrity (rupture, aneurysm) was observed in any group. Luminal narrowing was observed in both allograft groups, but secondary to different pathology. Fresh allografts had significant mononuclear cell infiltrate, intimal hyperplasia, and intramural hemorrhage consistent with rejection. Conversely, decellularized allografts had minimal evidence of rejection but instead had a compact fibrin layer formed along their lumen. This fibrin layer was absent in the peri-anastomotic regions where endothelium had migrated from the native artery. By 8 weeks, decellularized grafts had repopulated with cells staining positive for smooth muscle alpha-actin., Conclusions: After 8 weeks of arterial flow, decellularized vein allograft exhibits satisfactory strength, reduced antigenicity compared to fresh allograft, and supports cellular repopulation. These characteristics make it satisfactory for further tissue engineering; combined with luminal vascular cell seeding, it may prove useful as a small-diameter arterial bypass graft.

Aneurysm of the carotid artery following endarterectomy is a rare entity that historically has required reoperation. Endovascular deployment of a covered stent can theoretically exclude an aneurysm while minimizing the risks seen with reoperation. Herein, we review the scientific literature on this evolving technique and report an additional case involving successful treatment of an aneurysm that developed following remote endarterectomy.

Several studies have identified increased age as a risk factor for the development of cognitive impairment in human immunodeficiency virus (HIV)-infected subjects, but few have examined the potential synergistic effect of age and HIV serostatus on cognitive decline. The authors examined the possible combined effect of age and HIV serostatus on cognitive decline in 254 subjects stratified by age group and HIV status. After controlling for the effect of education, there were significant effects for serostatus and age group on overall cognitive impairment and a number of neuropsychological measures but no interaction effects. These data suggest that older seropositive individuals are not at an increased risk for HIV-related cognitive impairment when normal age-related cognitive changes are considered.

Objective: Residual subclavian vein stenosis after thoracic outlet decompression in patients with venous thoracic outlet syndrome is often treated with postoperative percutaneous angioplasty (PTA). However, interval recurrent thrombosis before postoperative angioplasty is performed can be a vexing problem. Therefore we initiated a prospective trial at 2 referral institutions to evaluate the safety and efficacy of combined thoracic outlet decompression with intraoperative PTA performed in 1 stage., Methods: Over 3 years 25 consecutive patients (16 women, 9 men; median age, 30 years) underwent treatment for venous thoracic outlet syndrome with a standard protocol at 2 institutions. Twenty-one patients (84%) underwent preoperative thrombolysis to treat axillosubclavian vein thrombosis. First-rib resection was performed through combined supraclavicular and infraclavicular incisions. Intraoperative venography and subclavian vein PTA were performed through a percutaneous basilic vein approach. Postoperative anticoagulation therapy was not used routinely. Venous duplex ultrasound scanning was performed postoperatively and at 1, 6, and 12 months., Results: Intraoperative venography enabled identification of residual subclavian vein stenosis in 16 patients (64%), and all underwent intraoperative PTA with 100% technical success. Postoperative duplex scans documented subclavian vein patency in 23 patients (92%). Complications included subclavian vein recurrent thrombosis in 2 patients (8%), and both underwent percutaneous mechanical thrombectomy, with restoration of patency in 1 patient. One-year primary and secondary patency rates were 92% and 96%, respectively, at life-table analysis., Conclusions: Residual subclavian vein stenosis after operative thoracic outlet decompression is common in patients with venous thoracic outlet syndrome. Combination treatment with surgical thoracic outlet decompression and intraoperative PTA is a safe and effective means for identifying and treating residual subclavian vein stenosis. Moreover, intraoperative PTA may reduce the incidence of postoperative recurrent thrombosis and eliminate the need for venous stent placement or open venous repair.

Purpose: Current strategies to create small-diameter vascular grafts involve seeding biocompatible, compliant scaffolds with autologous vascular cells. Our purpose was to study the composition and strength of decellularized vein to determine its potential as a vascular tissue-engineering scaffold., Methods: Intact human greater saphenous vein specimens were decellularized by using sodium dodecyl sulfate (SDS). Residual cellular and extracellular matrix composition was studied with light and electron microscopy as well as immunohistochemistry. Burst and suture-holding strength was measured in vitro by insufflation and pull-through techniques. To assess initial handling and durability of decellularized vein in vivo, a canine model was developed wherein decellularized canine jugular veins were implanted as carotid interposition grafts in recipient animals. After two weeks of arterial perfusion, these grafts were studied with duplex imaging and histologic methods., Results: Human saphenous vein decellularized by using SDS was devoid of endothelial cells and >94% of the cells resident within the vein wall. Collagen morphology appeared unchanged, and elastin staining decreased only slightly. Basement membrane collagen type IV remained intact. Compared with fresh vein, decellularized vein had similar in vitro burst (2480 +/- 460 mm Hg vs 2380 +/- 620 mm Hg; P >.05) and suture-holding (185 +/- 30 gm vs 178 +/- 66 gm; P >.05) strength. Decellularized canine vein functioned well in vivo without dilation, anastomotic complication, or rupture over 2 weeks of arterial perfusion., Conclusions: Vein rendered acellular with SDS has well-preserved extracellular matrix, basement membrane structure, and strength sufficient for vascular grafting. These properties suggest proof of concept for its use as a scaffold for further vascular tissue engineering., Clinical Relevance: The following research examines the creation of a new small-diameter bypass graft. It is clinically relevant to patients who need distal arterial bypass, coronary artery bypass, or hemodialysis access, but who do not have adequate autologous vein for their surgeries. Future investigations will involve further tissue engineering of this vascular scaffold (eg, autologous endothelial seeding of its lumen) and testing the clinical usefulness of the completed graft.

The effect of marijuana use on cognitive function is controversial. Although marijuana use is common in HIV-infected individuals for recreational and medicinal purposes, there have been no studies of the impact of marijuana on cognitive function in these subjects. Marijuana also has known immunologic effects, which increases the relevance in HIV-infected patients. We examined the interaction of HIV disease-stage and marijuana use in 282 subjects, stratified by disease stage and frequency of marijuana use. After controlling for the effects of depression, anxiety, and alcohol use, a significant interaction was observed on an overall measure of cognitive impairment. The effect of marijuana use was greatest in subjects with symptomatic HIV infection. Further inspection suggested that this effect was due primarily to performance on memory tasks. These data suggest that although there is minimal impact of marijuana on uninfected individuals or those at early stages of HIV infection, there is a synergistic effect of HIV and marijuana use in patients with advanced HIV disease. This is consistent with other data suggesting that the subtle effects of some conditions may become more manifest in the setting of immunocompromise.

Dicopper-[18]ane-N6 complex functions as a broad spectrum receptor for phosphate monoesters.

Previous studies have demonstrated an impact of stress on immune function, and recent studies have suggested an adverse effect of stress on the brain. However, no previous study has examined the impact of stress on cognitive function. This article examines the relationship between stress and cognitive function in 82 HIV-negative subjects and 251 HIV-positive subjects. Subjects completed a comprehensive neuropsychological examination, measures of anxiety and depression, and a measure of stressful life events. After controlling for the impact of anxiety, depression, age, and education, stressful life events were related to cognitive impairment only among the HIV-positive subjects. The data were interpreted in the context of previous studies that have demonstrated an adverse effect of stress on the brain and suggest that this adverse impact may be expressed in the setting of a compromised immune system. Furthermore, this analysis suggests several implications for patient management.

Normal development of the cerebral cortex requires long-range migration of cortical neurons from proliferative regions deep in the brain. Lissencephaly ("smooth brain," from "lissos," meaning smooth, and "encephalos," meaning brain) is a severe developmental disorder in which neuronal migration is impaired, leading to a thickened cerebral cortex whose normally folded contour is simplified and smooth. Two identified lissencephaly genes do not account for all known cases, and additional lissencephaly syndromes have been described. An autosomal recessive form of lissencephaly (LCH) associated with severe abnormalities of the cerebellum, hippocampus and brainstem maps to chromosome 7q22, and is associated with two independent mutations in the human gene encoding reelin (RELN). The mutations disrupt splicing of RELN cDNA, resulting in low or undetectable amounts of reelin protein. LCH parallels the reeler mouse mutant (Reln(rl)), in which Reln mutations cause cerebellar hypoplasia, abnormal cerebral cortical neuronal migration and abnormal axonal connectivity. RELN encodes a large (388 kD) secreted protein that acts on migrating cortical neurons by binding to the very low density lipoprotein receptor (VLDLR), the apolipoprotein E receptor 2 (ApoER2; refs 9-11 ), alpha3beta1 integrin and protocadherins. Although reelin was previously thought to function exclusively in brain, some humans with RELN mutations show abnormal neuromuscular connectivity and congenital lymphoedema, suggesting previously unsuspected functions for reelin in and outside of the brain.

We describe a sibship of three males, including monozygous twins, with cerebral and cerebellar malformations and congenital lymphedema. The parents of these children are related, being half second cousins. The clinical, radiologic and histopathologic features do not fit a previously recognized pattern. We feel this sibship represents a syndrome that has not been previously described, though it closely resembles the Walker Warburg syndrome.

A new method has been developed to evaluate the relative thrombogenicity of vascular catheters. The technique provides a means to quantitatively differentiate between catheters made from different polymeric materials. Autologous In-111 labeled platelets were infused into a dog model and catheters were then inserted into the external jugular vein of the dog. The neck region was scanned using gamma camera imaging. Comparisons between catheter materials were made using computer generated uptake slopes during the first 40 min of the scan. In addition to scintigraphy, visual assessment of thrombus deposition, thrombus weight, platelet deposition, and scanning electron microscopy were used to validate the technique. Poly(vinyl chloride), polyurethane, heparinized polyurethane, and silicone catheter materials were tested. It was found that heparinized polyurethane was the least thrombogenic of all materials evaluated.

Images of 7 patients with primary amyloidosis revealed organomegaly with regions of decreased tracer accumulation due to infiltration and replacement of normal tissue by the amyloid complex. These scintigraphic changes in the clinical setting of multisystem disease should suggest amyloidosis as a possible diagnosis.

The authors studied changes in indices of thyroid function prospectively in a group of 11 patients given amitriptyline to treat depression. The drug caused no significant alteration in these indices, but scores on the Hamilton Depression Rating Scale improved significantly. In another group of subjects with depression, the stimulation of growth hormone secretion by L-dopa was unaffected by amitriptyline therapy.

Marked physiological reactivity to challenging mental tasks has been associated with elevated risk for, as well as the presence of, coronary heart disease. However, little systematic enquiry into the reliability and quantification of such exaggerated reactivity has emerged. Subjects were 32 male, managerial employees, ranging in age from 22 to 56 yr, who satisfied the following criteria: no history or current signs of heart disease, presence of Type A behavior pattern as revealed by the Structured Interview, and an increase during an initial psychosocial stress testing of at least 25% over baseline in at least three out of five psychophysiological indices. Heart rate, systolic blood pressure, diastolic blood pressure, plasma epinephrine and plasma norepinephrine levels were monitored while challenging mental tasks were performed in three sessions (screening, pretraining and posttraining) spaced several weeks apart. Psychophysiological reactivity during the tasks emerged as a consistent trait. For all five measures, change scores from baseline during the screening session were significantly correlated with change scores during the pretraining session. Moreover, the magnitude of the change scores were similar in the screening and pretraining sessions. Analysis of cross correlations within and between indices provided little support for the use of data transformations such as residual scores or analysis of covariance. Finally, on four out of five measures, the challenging tasks were found to be comparable in the degree of reactivity elicited. These findings suggest that, for selected Type A men, exaggerated psychophysiological reactivity occurs reliably when monitored with multiple indices, appears insensitive to mere passage of time, and can be uniformly elicited by a variety of tasks.

Using a triiodothyronine withdrawal method to produce a hypothyroid state in 38 patients with prior thyroidectomies for differentiated thyroid cancer, 56 H-TSH and T4 levels were measured prior to metastatic survey scans performed with 131I. All the T4 levels were below normal and 55 of the 56 H-TSH levels were elevated. No qualitative differences could be observed in the eight patients who had scans performed after bovine TSH injections and later after triiodothyronine withdrawal. Triiodothyronine withdrawal does induce high endogenous TSH levels and under normal circumstances bovine TSH injections are not required for metastatic scans in patients with thyroid cancer.

Noninvasive myocardial imaging with potassium-43 and rubidium-81 has been used successfully to identify areas of infarction and exercise-induced ischemia as regions of decreased radioactivity. The image defects observed are believed to be due to a decreased radionuclide uptake in regions of myocardial scar or to heterogeneous myocardial accumulation of tracer as a result of regional ischemia. Of 27 patients with left bundle branch block studied with noninvasive imaging at rest and during exercise, 25 manifested at rest reduced radioactivity in the region of the interventricular septum. This pattern is similar to that seen in patients with anteroseptal myocardial infarction. Sixteen of the 27 patients underwent diagnostic coronary arteriography and left ventriculography. Only five of these patients had evidence of either previous infarction or significant obstructive coronary artery disease as assessed with clinical or angiographic criteria, or both. Although the image defect was routinely demonstrated at rest in patients with left bundle branch block, this defect was generally normalized or less distinct with exercise in patients with no anatomic heart disease. In contrast, a larger, more distinct or new image defect with exercise correctly identified the presence of significant obstructive coronary artery disease in patients with left bundle branch block. In the clinical application of noninvasive myocardial imaging, these image defects observed at rest can lead to the false pasitive radionuclide interpretation of anteroseptal myocardial infarction.

A patient with acute sarcoidosis is described who presented with pleurisy and bilateral pleural effusions, but no other abnormalities on examination or chest X-ray. This presentation of sarcoidosis is unusual and is discussed.

Metabolites of vitamin D were measured in plasma from 83 patients with idiopathic infantile hypercalcaemia syndrome who were mentally handicapped but had normal calcium values at the time of the study. No significant difference was detected in the mean plasma concentrations of 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D3, or 25,26-dihydroxyvitamin D3 between patients and age matched controls. The mean plasma concentration of 25-hydroxyvitamin D3 was significantly lower in patients than controls but this may be a secondary phenomenon related to less sunlight exposure. In addition, two hypercalcaemic patients with this syndrome were studied during the first year of life, and were found to have normal concentrations of vitamin D metabolites. These findings do not support a role for abnormal vitamin D metabolism in the pathogenesis of this syndrome.

Seventy six children with documented Fanconi-type idiopathic infantile hypercalcaemia were studied and compared with 41 with the Williams-Beuren syndrome. Clinical comparison showed, as expected, very close similarities but also considerable differences, particularly in the severity of feeding problems and the degree of failure to thrive. The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom (1 per 47 000 total live births). Long term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%), and obesity (50%) may be added complications. In one child, hypercalcaemia recurred during adolescence but this seems to be excessively rare. More detailed investigation before treatment is required to discover the aetiology of hypercalcaemia in this condition.

Forty three children aged 6 to 16 years with a documented history of idiopathic infantile hypercalcaemia were assessed on a variety of cognitive and behavioural measures. No relation was found between the age at which hypercalcaemia was diagnosed and subsequent full scale intelligence quotients (IQ) and reading or spelling abilities. Verbal IQ was, however, significantly higher than performance IQ, which had an inverse relation with age at diagnosis. Furthermore, scores for deviant behaviour were found to correlate with age at diagnosis. Thus the characteristic psychological profile of this syndrome may be in part a function of hypercalcaemia during infancy.

Chlorpropamide was found to be an effective antidiuretic agent in vasopressin-sensitive diabetes insipidus. Full clinical use of this action is limited by the frequent occurrence of hypoglycemia on higher doses. This complication can be avoided, however, by restricting the dose and by employing combination therapy with hydrochlorothiazide.