Biomarker-specific biosensors revolutionise breast cancer diagnosis.

Breast cancer is the most common cancer among women across the globe. In order to treat breast cancer successfully, it is crucial to conduct a comprehensive assessment of the condition during its initial stages. Although mammogram screening has long been a common method of breast cancer screening, high rates of type I error and type II error results as well as radiation exposure have always been of concern. The outgrowth cancer mortality rate is primarily due to delayed diagnosis, which occurs most frequently in a metastatic III or IV stage, resulting in a poor prognosis after therapy. Traditional detection techniques require identifying carcinogenic properties of cells, such as DNA or RNA alterations, conformational changes and overexpression of certain proteins, and cell shape, which are referred to as biomarkers or analytes. These procedures are complex, long-drawn-out, and expensive. Biosensors have recently acquired appeal as low-cost, simple, and super sensitive detection methods for analysis. The biosensor approach requires the existence of biomarkers in the sample. Thus, the development of novel molecular markers for diverse forms of cancer is a rising complementary affair. These biosensor devices offer two major advantages: (1) a tiny amount of blood collected from the patient is sufficient for analysis, and (2) it could help clinicians swiftly select and decide on the best therapy routine for the individual. This review will include updates on prospective cancer markers and biosensors in cancer diagnosis, as well as the associated detection limitations, with a focus on biosensor development for marker detection.

Association of blood pressure with neurologic outcome at hospital discharge after pediatric cardiac arrest resuscitation.

BACKGROUND: Poor outcomes are associated with post cardiac arrest blood pressures <5th percentile for age. We aimed to study the relationship of mean arterial pressure (MAP) with favorable neurologic outcome following cardiac arrest and return of spontaneous circulation (ROSC). METHODS: This retrospective, multi-center, observational study analyzed data from the Pediatric Resuscitation Quality Collaborative (pediRES-Q). Children (<18 years) who achieved ROSC following index in-hospital or out-of-hospital cardiac arrest and survived ≥6 hours were included. Lowest documented MAP within the first 6 hours of ROSC was percentile adjusted for age and categorized into six groups - Group I: <5th, II: 5-24th, III: 25-49th, IV: 50-74th, V: 75-94th; and VI: 95-100th percentile. Primary outcome was favorable neurologic status at hospital discharge, defined as PCPC score 1, 2, or no change from pre-arrest baseline. Multivariable logistic regression was performed to analyze the association of MAP group with favorable outcome, controlling for illness category (surgical-cardiac), initial rhythm (shockable), arrest time (weekend or overnight), age, CPR duration, and clustering by site. RESULTS: 787 patients were included: median [Q1,Q3] age 17.9 [4.8,90.6] months; male 58%; OHCA 21%; shockable rhythm 13%; CPR duration 7 [3,16] min; favorable neurologic outcome 54%. Median lowest documented MAP percentile for the favorable outcome group was 13 [3,43] versus 8 [1,37] for the unfavorable group. The distribution of blood pressures by MAP group was I: 37%, II: 28%, III: 13%, IV: 11%, V: 7%, and VI: 4%. Compared with patients in Group I (<5%ile), Groups II, III, and IV had higher odds of favorable outcome (aOR, 1.84 [95% CI, 1.24, 2.73]; 2.20 [95% CI, 1.32, 3.68]; 1.90 [95% CI, 1.12, 3.25]). There was no association between Groups V or VI and favorable outcome (aOR, 1.44 [95% CI, 0.75, 2.80]; 1.11 [95% CI, 0.47, 2.59]). CONCLUSION: In the first 6-hours post-ROSC, a lowest documented MAP between the 5th-74th percentile for age was associated with favorable neurologic outcome compared to MAP <5th percentile for age.

Biomarkers and biosensors for early cancer diagnosis, monitoring and prognosis.

Cancers continue to be of major concern due to their serious global socioeconomic impact, apart from the continued increase in the incidence of various cancer types. A major challenge that this disease poses is due to the low "early detection" rates which limit the therapeutic outcomes for the affected individuals. Current research has highlighted the discovering biomarkers that help in early cancer detection and the development of technologies for the detection and quantification of such biomarkers. Biomarkers range from proteins to nucleic acids, and can be specific to a particular cancer type. Detection and quantification of such biomarkers at low levels from biological samples is being made possible by the advent of developing biosensors and by using biomedical engineering technologies such as tumor-on-a-chip models. Here, we present biomarkers that can be helpful for the early detection of breast, colorectal, esophageal, lung, liver, ovarian, and prostate cancer. In addition, we discuss the potential of circulating tumor cell DNA (ctDNA) as an early diagnostic marker. Finally, biosensors available for the detection of cancer biomarkers, which is a recent advancement in this area of research, are discussed.

The Hunter-8 Scale Prehospital Triage Workflow for Identification of Large Vessel Occlusion and Brain Haemorrhage.

OBJECTIVE: The Hunter-8 prehospital stroke scale predicts large vessel occlusion in hyperacute ischemic stroke patients (LVO) at hospital admission. We wished to test its performance in the hands of paramedics as part of a prehospital triage algorithm. We aimed to determine (a) the proportion of patients identified by the Hunter-8 algorithm, receiving reperfusion therapies, (b) whether a call to stroke team improved this, and (c) performance for LVO detection using an expanded LVO definition. METHODS: A prehospital workflow combining pre-morbid functional status, time from symptom onset, and the Hunter-8 scale was implemented from July 2019. A telephone call to the stroke team was prompted for potential treatment candidates. Classic LVO was defined as a proximal middle cerebral artery (MCA-M1), terminal internal carotid artery, or tandem occlusion. Extended LVO added proximal MCA-M2 and basilar occlusions. RESULTS: From July 2019 to April 2021, there were 363 Hunter-8 activations, 320 analyzed: 181 (56.6%) had confirmed ischemic strokes, 13 (4.1%) transient ischemic attack, 91 (28.5%) stroke mimics, and 35 (10.9%) intracranial hemorrhage. Fifty-two patients (16.3%) received reperfusion therapies, 35 with Hunter-8 ≥ 8. The stroke doctor changed the final destination for 76 patients (23.7%), and five received reperfusion therapies. The AUCs for classic and extended LVO were 0.73 (95% CI 0.66-0.79) and 0.72 (95% CI 0.65-0.77), respectively. CONCLUSION: The Hunter-8 workflow resulted in 28.7% of confirmed ischemic stroke patients receiving reperfusion therapies, with no secondary transfers to the comprehensive stroke center. The role of communication with stroke team needs to be further explored.

Diabetes in adults with intellectual disability: prevalence and associated demographic, lifestyle, independence and health factors.

BACKGROUND: As people with intellectual disabilities (ID) are now living longer, they are more at risk of developing non-communicable diseases, including type 2 diabetes mellitus. However, understanding of factors associated with diabetes for targeted management and prevention strategies is limited. This study aimed to investigate prevalence of diabetes in adults (aged ≥18 years) with ID and its relationship with demographic, lifestyle, independence and health factors. METHOD: This was a cross-sectional analysis of interview data from 1091 adults with ID from the Leicestershire Learning Disability Register from 1 January 2010 to 31 December 2016. Logistic regression models were used to identify factors associated with diabetes in the study population. RESULTS: The study population did not have healthy lifestyles: just under half reported having lower physical activity levels than people without ID of a similar age; one-quarter consumed fizzy drinks daily; and 20% consumed five or more fruit and/or vegetables per day. Prevalence of carer/self-reported diabetes was 7.3% (95% confidence interval 5.9-9.0). After adjustment, diabetes was positively associated with South Asian ethnicity (P = 0.03) and older age groups (P < 0.001). Diabetes was less common in people living with family members (P = 0.02). We did not find a relationship between any of the lifestyle, independence and health factors investigated. CONCLUSIONS: A significant proportion of people with ID are living with diabetes. Diabetes management and prevention strategies should be tailored to individuals' complex needs and include consideration of lifestyle choices. Such strategies may want to focus on adults of South Asian ethnicity and people living in residential homes where prevalence appears to be higher.

Characteristics and outcomes of patients with intellectual disability admitted to a specialist inpatient rehabilitation service.

Rehabilitation services for people with mental illnesses have been extensively researched. However, services with similar aims and specifications for patients with intellectual disabilities (IDs) have had little focus. This study describes the characteristics and outcomes of 21 patients admitted to a specialist ID rehabilitation service over an 8-year time frame. Rather that solely accepting 'step-down' referrals, some patients were referred from community settings. During the study, 20 patients were discharged, 80% to lower levels of service restriction, while 14.3% to higher levels. The study suggested that rehabilitation services have an important role within the wider service model for people with ID. Within the service studied, patients were referred from both higher and lower levels of restriction, suggesting the rehabilitation service 'bridged the gap' between inpatient and community settings, supporting the aim of caring for patients in the least restrictive setting for their needs.

Development of a multi-component lifestyle intervention for preventing type 2 diabetes and cardiovascular risk factors in adults with intellectual disabilities.

Background: We report on the development of the 'STOP Diabetes' education programme, a multi-component lifestyle behaviour change intervention for the prevention of type 2 diabetes and cardiovascular risk factors in adults with intellectual disabilities (ID). Methods: We combined qualitative stakeholder interviews with evidence reviews to develop the intervention, guided by the MRC Framework and informed by intervention mapping and two existing diabetes prevention programmes. We conducted two pilot cycles drawing on additional stakeholder interviews to inform and refine the intervention. Results: The STOP Diabetes education programme employed a theoretical framework, using sound learning and behavioural principles and concrete kinaesthetic methods, to provide the grounding for innovative games and activities to promote health behaviour change in adults with ID. Qualitative data also suggested that two educators and one support person delivering a programme of one carer session followed by seven 2.5-h sessions over 7 weeks was acceptable to service users, carers and educators and appeared to benefit the participants. Conclusions: The STOP Diabetes education programme was successfully developed and is suitable for a definitive randomized controlled trial.

Comparison of rocuronium at two different doses and succinylcholine for endotracheal intubation in adult patients for elective surgeries.

BACKGROUND: The effects of rocuronium at two different doses, that is, 0.6 mg/kg (2 × ED95) and 0.9 mg/kg (3 × ED95), were compared with succinylcholine (2 mg/kg) when used for endotracheal intubation in adult patients for elective surgeries under general anesthesia. MATERIALS AND METHODS: Ninety patients were divided into three groups of 30 each. Groups A, B received injection rocuronium at 0.6 mg/kg, 0.9 mg/kg respectively and Group C received succinylcholine at 2 mg/kg. Onset of action of relaxant, intubation conditions, time taken to intubate and duration of action were compared. STATISTICAL ANALYSIS USED: To compare the statistical difference in the age, weight, height of the study subjects, onset of action of relaxant, intubation conditions, time taken to intubate, and duration of action analysis of variance and unpaired t-test were used. RESULTS: The onset time was considerably shorter with rocuronium 0.9 mg/kg than 0.6 mg/kg. The onset time of rocuronium 0.9 mg/kg was found to be significantly longer than succinylcholine 2 mg/kg. Time taken to intubate was shortest with succinylcholine 2 mg/kg. The time taken to intubate with the rocuronium 0.9 mg/kg was found to be comparable to that of rocuronium 0.6 mg/kg. Intubation score of rocuronium 0.9 mg/kg was the best (17.75), which was comparable with succinylcholine. However, the intubation score obtained with rocuronium 0.6 mg/kg was inferior. Duration of action was shortest with succinylcholine. The duration of action is prolonged when the dose of rocuronium is increased from 0.6 to 0.9 mg/kg. CONCLUSION: Rapid sequence induction of anesthesia with propofol and fentanyl, succinylcholine allowed a more rapid endotracheal intubation sequence and created superior intubation conditions than rocuronium. However, the technique of using a large dose of rocuronium to achieve perfect conditions for tracheal intubation may have application whenever succinylcholine is relatively contraindicated.

Subcarinal collection following mediastinoscopy: a normal post-procedural CT finding.

AIM: To determine the frequency with which a subcarinal collection is present at computed tomography (CT) following mediastinoscopy and to determine the CT features of the collection. MATERIALS AND METHODS: All patients who underwent uncomplicated mediastinoscopy during a 1-year period were retrospectively identified. This list was cross-referenced to determine those patients who also underwent CT within 15 days after the procedure. Each post-mediastinoscopy CT examination was assessed in consensus by three fellowship-trained thoracic radiologists for the presence of subcarinal abnormalities, which were also characterized in terms of their size and density. Additional CT findings were recorded, including tracheobronchial wall thickening, paratracheal collections, mediastinal fat stranding, and mediastinal air. RESULTS: The study cohort included 10 patients (seven men and three women) with mean age of 65 years (range 49-81 years). CT was performed a mean of 11 days following mediastinoscopy. The most common CT finding was an oval subcarinal collection in nine of 10 cases (size 1.1-3.2 cm). In all nine cases, the subcarinal collections were consistently lower in attenuation than the subcarinal lymph node in the same region on the pre-procedure CT examination. Other CT findings included anterior tracheobronchial wall thickening (n=7); paratracheal collection (n=6); mediastinal fat stranding (n=6); and mediastinal air in (n=4) cases. CONCLUSION: A subcarinal collection was identified in 90% of cases following mediastinoscopy. Its rapid development and characteristic appearance help to distinguish it from a lymph node.

Personality disorders in offenders with intellectual disability: a comparison of clinical, forensic and outcome variables and implications for service provision.

AIM: To establish any differences between patients with and without a diagnosis of personality disorders, being treated in a secure inpatient service for offenders with intellectual disability (ID) in the UK. METHOD: A cohort study involving a selected population of people with ID and offending behaviours. Results The study included a total of 138 patients, treated over a 6 year period - 77 with a dissocial or emotionally unstable personality disorder and 61 without. Women were more likely to be in the personality disorder group. Both groups had high prevalence of abuse with no significant differences. Depressive disorders and substance abuse were more common in the personality disorder group, while epilepsy and autistic spectrum disorders were more common in the non-personality disorder group. Rather than differences, what was more striking was the rate and range of these comorbidities across both groups. Although past histories of violence and institutional aggression were no different, compulsory detention under criminal sections and restriction orders were more common in the personality disorder group. There were no differences in treatment outcomes. CONCLUSIONS: Although about half of patients detained in secure units for offenders with ID have a personality disorder, there were more similarities than differences between this group and the rest. While good treatment outcomes supported the case for specialised secure treatment units for people with ID, the case for establishing a more specialised ID-personality disorder unit was less convincing. There is also a need to explore whether there are alternative diagnostic models that can delineate better the group with personality difficulties in this population.

Satellite-tagged transcribing sequences in Bubalus bubalis genome undergo programmed modulation in meiocytes: possible implications for transcriptional inactivation.

We cloned and sequenced a 1378 bp BamHI satellite DNA fraction from the water buffalo Bubalus bubalis and have studied its expression in different tissues. The GC-rich sequences of the resultant contig pDS5 crosshybridize only with bovid DNA and are not conserved evolutionarily. Typing of buffalo genomic DNA using pDS5 with several restriction enzymes revealed multilocus monomorphic bands. Similar typing of cattle, buffalo, goat, sheep, and gaur genomic DNA revealed variations in copy number and allele length giving rise to species-specific band patterns. Expression study of pDS5 in bubaline samples by RNA slot-blot, Northern blot, and RT-PCR showed various levels of signal in all the somatic tissues and germline cells except heart. A GenBank database search revealed homology of pDS5 sequences in the 5' region from nt 1-1261 with collagen gene. An AluI typing analysis of DNA from bubaline semen samples showed consistent loss of two bands. The presence of corresponding bands in somatic tissues suggests a sequence modulation within the pDS5 array in meiocytes during spermatogenesis, which is restored in the somatic cells after fertilization. Modulation of the satellite-tagged transcribing sequence in the meiocytes may be a mechanism of its inactivation.

Monocyte adhesion to human vein grafts: a marker for occult intraoperative injury?

OBJECTIVE: Monocyte adhesion to the vessel wall is believed to be an important initiating event in atherosclerosis and intimal hyperplasia. We hypothesized that occult intraoperative vein injury induces an immediate increase in monocyte adhesion that may be critical to the development of vein graft disease. METHODS: Vein segments were obtained from patients (n = 23) undergoing lower extremity bypass. The initial segment (V1, n = 17) was excised immediately at the time of conduit harvest. A second segment (V2, n = 23) was obtained from the distal conduit just before performing the distal anastomosis. Segments were incubated with radiolabeled THP-1 cells (monocytoid cell line) for 1 hour at 37 degrees C, then rinsed and solubilized for determination of bound radioactivity. In a subset of grafts (n = 4), THP-1 cells were preincubated with monoclonal antibody (mAB) 7E3 (which binds to the monocyte integrin Mac-1 at its fibrinogen [Fg]-binding site) or control (mAB 14E11). Fg deposition and endothelial coverage were evaluated by immunohistochemistry (n = 10). Statistical analysis was performed using the paired t test and analysis of variance. Follow-up graft patency data were obtained and correlated with adhesion values using an exact test (StatXact, Cytel Software, Cambridge, Mass). RESULTS: Monocyte adhesion was significantly increased after surgical manipulation (V1, 2400 +/- 770 versus V2, 7343 +/- 1555 cells/cm(2); P <.02). Fg deposition was abundant in V2 sections and not seen in V1. Monocyte adhesion to V2 segments was significantly reduced (58% of control, P <.01) by 7E3 treatment. Graft follow-up was complete with a mean interval of 11 months. Higher V2 adhesion values were associated with occluded grafts (P =.07). The median value for the six occluded grafts was 6234 cells/cm(2) versus 3892 cells/cm(2) for the 17 patent grafts. CONCLUSIONS: Monocyte adhesion to the vein wall is immediately increased after surgical manipulation and is inhibited by mAB 7E3. Early monocyte adhesion to vein grafts is likely to involve interactions between Mac-1 and Fg. Heightened levels of monocyte adhesion at implantation may be a marker for subsequent vein graft failure.

Targeting platelet aggregation: CD39 gene transfer augments nucleoside triphosphate diphosphohydrolase activity in injured rabbit arteries.

BACKGROUND: CD39, the major endothelial nucleoside triphosphate diphosphohydrolase (NTPDase), plays an important role in local thromboregulation. We hypothesized that balloon injury (BI) leads to an acute reduction in arterial NTPDase activity that could be restored by a targeted gene delivery strategy. METHODS: Recombinant adenoviral vectors containing human CD39 (Ad-CD39) or beta-galactosidase (Ad-LacZ) were used. Endothelial (ECs) and smooth muscle cells (SMCs) were infected in vitro and NTPDase activity measured. New Zealand white rabbits (N = 28) underwent bilateral iliofemoral artery balloon injury, followed by incubation with Ad-CD39, Ad-LacZ, or vehicle. Explanted vessels were analyzed for NTPDase activity and localization of CD39 expression by immunohistochemistry. Deposition of fluorescent-labeled platelets was studied 3 days after injury and vector treatment. RESULTS: In vitro, Ad-CD39 infection resulted in a greater than 40-fold increase in adenosine diphosphatase activity in ECs and a 3-fold increase in SMCs. In vivo, CD39 transgene expression localized to the luminal aspect of Ad-CD39--treated vessels. BI resulted in an acute reduction in vessel wall NTPDase activity (P <.05). Ad-CD39 augmented NTPDase activity when compared with vehicle or Ad-LacZ (P <.05). Platelet deposition on the injured arterial surface was modest and not different between Ad-CD39-- and Ad-LacZ--treated vessels. CONCLUSIONS: BI decreases native NTPDase activity, which can be augmented by adenovirus-mediated gene transfer of CD39. Further studies are required to determine whether targeted delivery of CD39 could convey thromboprotective properties to an injured vessel.

Monocyte adhesion to balloon-injured arteries: the influence of endothelial cell seeding.

OBJECTIVE: Deendothelialization of injuries of the artery disrupts normal vascular homeostasis, affecting both the structural integrity of the blood vessel wall, as well as the interaction of the arterial surface with blood components such as platelets, leukocytes, and circulating proteins. Leukocyte and, in particular, monocyte recruitment to damaged vessels has been implicated in the pathogenesis of intimal hyperplasia. We hypothesize that reendothelialization is an important modulator of monocyte adhesion to healing arterial surfaces. METHODS: New Zealand white rabbits (n = 20) were subjected to bilateral iliofemoral artery balloon injury. Cultured, autologous venous endothelial cells (ECs) were immediately seeded onto one vessel, whereas the contralateral artery received medium alone, to accelerate endothelial relining. Vessels were harvested (5-9 days after injury) for analysis of permeability (Evans Blue dye exclusion), endothelial coverage (anti-CD31 immunohistochemistry), monocyte adhesion (ex vivo binding of 51Na2CrO4-labeled monocytic THP-1 cells), and monocyte recruitment (RAM-11 immunohistochemistry). RESULTS: Improved EC coverage was evidenced by positive staining for CD31 in the seeded vessels. Vessel wall permeability was markedly reduced in EC-seeded arteries (29% +/- 10% vs 99% +/- 0% surface Evans blue staining, P <.005), consistent with restoration of a functional endothelial barrier. EC seeding significantly reduced ex vivo THP-1 binding to vessels explanted at a mean of 8 days after injury (45,170 +/- 8939 vs 85,994 +/- 16,500 cells/cm2, P <.05). However, RAM-11 staining revealed no significant difference in overall macrophage accumulation between seeded and control vessels 1 week after injury (111 +/- 22 vs 95 +/- 14 cells/section, P =.36). CONCLUSIONS: Immediate seeding of a balloon-injured rabbit artery with cultured ECs results in accelerated restoration of the endothelial lining. At 1 week, barrier function is improved, and the seeded vessel surface is less adhesive to activated monocytes ex vivo, as compared with injured controls. Nonetheless, EC-seeded and nonseeded arteries demonstrate similar total macrophage accumulation over 1 week. These data suggest that after mechanical arterial injury, endothelial coverage may be one important variable influencing leukocyte adhesion.

Epilepsy and EEG findings in 18 males with fragile X syndrome.

Of the 24 males identified as having fragile X syndrome in the Northeast Essex screening programme, 25% had epilepsy. Epilepsy in individuals with fragile X syndrome is known to follow a benign course with seizures disappearing before the age of 20. However, half of our sample with a history of epilepsy continued to have seizures after the age of 20. We reviewed the EEG reports of 18 of the 24 individuals (aged between 13 and 63 years) including all six individuals with epilepsy. We had 32 EEG recordings from 18 subjects, with nine people having more than one recording at different points. The EEG showed a definite improvement in only five individuals. Three individuals who had serial recordings (one with epilepsy) showed no significant changes over time and the EEG of one subject with epilepsy deteriorated. The most common abnormal EEG findings were rhythmic theta activity (50%) and a slowing of background activity (28%). There were no characteristic features in the sleep EEGs performed on four subjects. The possible implications of these preliminary findings are discussed.

Corneal endothelial cell density and morphology in normal Indian eyes.

PURPOSE: To describe corneal endothelial cell density and morphology in the Indian population and to compare endothelial cell characteristics in the Indian population with data available in literature for American and Japanese populations. METHODS: Specular microscopy and corneal pachymetry were performed in both eyes of 537 normal Indian volunteers, aged 20-87 years. Parameters studied included endothelial cell density, cell area, coefficient of variation (CV) in cell area and hexagonality. RESULTS: Mean endothelial cell density in the study population was 2,525 +/- 337 cells/mm2. There was a statistically significant decrease in endothelial cell density with age (p < 0.001, correlation -0.387) and the rate of cell loss was 0.3% per year. There was also a statistically significant increase in mean cell area (p < 0.001, correlation 0.362) and CV (p = 0.02, correlation 0.096), and decrease in percentage of hexagonal cells (p = 0.01, correlation -0.127) with increasing age. There was no significant difference in these parameters between fellow eyes of subjects. In all age groups, the mean endothelial cell density was significantly lower than values reported previously in the Japanese population. The values were less than those described in the American population, but the differences were statistically significant only in the 20-30 and 41-50 year age groups. CONCLUSION: Normative data for the endothelium in the Indian population are reported. Endothelial cell density in Indian eyes is less than the values described in the Japanese and American populations.

Gene delivery to in situ veins: differential effects of adenovirus and adeno-associated viral vectors.

PURPOSE: Gene transfer offers the potential to modify vein graft biology at the time of surgical implantation. Efficiency of gene delivery, stability of expression, and host responses are critical parameters for candidate vectors. We compared the effects of intraluminal exposure with adenovirus (AD) and adeno-associated virus (AAV) vectors on transgene expression and monocyte adhesion (MA) in treated vein segments. METHODS: Adult New Zealand white rabbits (N = 51) were anesthetized, and the jugular veins were cannulated bilaterally. Veins were gently distended with either vector (2.10(8) to 1.10(10) infective particles/mL) or vehicle (control) for 30 minutes, after which venous flow was restored. AD and AAV vectors encoding for the marker genes beta-galactosidase (LacZ) and green fluorescent protein (GFP) were used. Vessels were explanted 2 to 40 days postinfection for analysis of gene expression (X-gal staining, reverse transcriptase-polymerase chain reaction), MA, and immunohistochemistry. Ex vivo adhesion assays used (51)Cr-labeled THP-1 cells. Statistical significance was tested by using analysis of variance with a P value less than.05. RESULTS: All animals survived, and all treated veins were patent at sacrifice. Intraluminal exposure to AD at a titer of 1.10(9) resulted in near complete transduction of the endothelium at 2 days, with no detectable expression by day 14. At an equal titer of infectious particles, transgene expression was markedly less for AAV at 2 to 7 days, but improved at 2 weeks and persisted to 40 days. MA was significantly increased 2 days after AD exposure (2.7-fold vs control, *P <.002); AAV treatment had no discernible effect on MA. CONCLUSION: AD-mediated gene transfer to vein segments resulted in robust, transient gene expression that disappeared after 2 weeks. In comparison, AAV-mediated gene delivery was less efficient, but resulted in delayed onset, persistent expression beyond 30 days. AD exposure induced an early increase in MA to the vein surface that was not seen with AAV treatment. Current generations of both AD and AAV vectors have significant, albeit different, limitations for vascular gene therapy.