Are clinical outcomes affected by laminoplasty method and K-line in patients with cervical ossification of posterior longitudinal ligament? A multicenter study.

BACKGROUND: Open-door laminoplasty (ODL) and French-door laminoplasty (FDL) are the main laminoplasty techniques used to treat cervical ossification of the posterior longitudinal ligament (C-OPLL). However, few studies have compared the outcomes of ODL and modified FDL (mFDL) for C-OPLL. We explored the differences in outcomes between ODL and mFDL for C-OPLL and analyzed the technical efficacy of each procedure in patients with K-line (+) or (-) C-OPLL. METHODS: From January 2010 to December 2015, 202 patients with K-line (+) or (-) C-OPLL were retrospectively recruited from 4 institutions. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA score recovery rate, operative time, blood loss, and complications. Univariate analysis and binary logistic regression models were adjusted for confounding factors. RESULTS: Two hundred patients (mFDL, n = 69; ODL, n = 131) with a median follow-up of 42 months (range 36-54 months) were included. The postoperative JOA score significantly improved in both groups (P < 0.05). After adjusting for confounding factors, there was a statistically significant difference in blood loss (≥ 300 mL) between the two groups (P = 0.005), but there was no significant difference in the postoperative JOA score (≥ 14) (P = 0.062), JOA score recovery rate (≥ 0.82) (P = 0.187), or operative time (≥ 90 min) (P = 0.925). C5 palsy tended to occur more often in the mFDL group, although the difference was not significant (P > 0.05). The stratified analysis of the K-line status showed more blood loss in K-line (+) patients who underwent mFDL, but there was no significant difference in the postoperative JOA score, JOA score recovery rate, or operative time between the ODL and mFDL groups. Additionally, there was no significant difference in blood loss, postoperative JOA score, JOA score recovery rate, or operative time among all patients with K-line (+) or (-) C-OPLL in both groups. CONCLUSIONS: Both ODL and mFDL are effective for patients with C-OPLL. However, more blood loss tends to occur during mFDL. This study showed no significant difference in the operative time or incidence of complications between the two techniques. The efficacy of ODL and mFDL was not affected by the K-line status (+ or -) in patients with C-OPLL.

The changing HIV-1 genetic characteristics and transmitted drug resistance among recently infected population in Yunnan, China.

Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991-1999 and 1994-1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994-1998 and 2001-2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

Long-Term Follow-Up Results following Elective Treatment of Unruptured Intracranial Aneurysms with the Pipeline Embolization Device.

BACKGROUND AND PURPOSE: Numerous reports of treatment of wide-neck aneurysms by flow diverters have been published; however, long-term outcomes remain uncertain. This article reports the imaging results of unruptured aneurysms treated electively with the Pipeline Embolization Device for up to 56 months and clinical results for up to 61 months. MATERIALS AND METHODS: One hundred nineteen aneurysms in 98 patients from 3 centers admitted between August 2009 and June 2011 were followed at 6-month, 1-year, and 2+-year postprocedural timeframes. Analyses on the effects of incorporated vessels, previous stent placement, aneurysm size, and morphology on aneurysm occlusion were performed. RESULTS: The 1- and 2+-year imaging follow-ups were performed, on average, 13 and 28 months postprocedure. At 2+-year follow-up, clinical data were 100% complete and imaging data were complete for 103/116 aneurysms (88.8%) with a 93.2% occlusion rate. From 0 to 6 months, TIA, minor stroke, and major stroke rates were 4.2%, 3.4%, and 0.8% respectively. After 6 months, 1 patient had a TIA of uncertain cause, with an overall Pipeline Embolization Device-related mortality rate of 0.8%. An incorporated vessel was significant for a delay in occlusion (P = .009) and nonocclusion at 6 months and 1 year, with a delayed mean time of occlusion from 9.1 months (95% CI, 7.1-11.1 months) to 16.7 months (95% CI, 11.4-22.0 months). Other factors were nonsignificant. CONCLUSIONS: The Pipeline Embolization Device demonstrates continued very high closure rates at 2+ years, with few delayed clinical adverse sequelae. The presence of an incorporated vessel in the wall of the aneurysm causes a delay in occlusion that approaches sidewall closure rates by 2 years.

Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma.

Zinc-finger, MYND-type containing 10 (ZMYND10), or more commonly called BLU, expression is frequently downregulated in nasopharyngeal carcinoma (NPC) and many other tumors due to promoter hypermethylation. Functional evidence shows that the BLU gene inhibits tumor growth in animal assays, but the detailed molecular mechanism responsible for this is still not well understood. In current studies, we find that 93.5% of early-stage primary NPC tumors show downregulated BLU expression. Using a PCR array, overexpression of the BLU gene was correlated to the angiogenesis network in NPC cells. Moreover, expression changes of the MMP family, VEGF and TSP1, were often detected in different stages of NPC, suggesting the possibility that BLU may be directly involved in the microenvironment and anti-angiogenic activity in NPC development. Compared with vector-alone control cells, BLU stable transfectants, derived from poorly-differentiated NPC HONE1 cells, suppress VEGF165, VEGF189 and TSP1 expression at both the RNA and protein levels, and significantly reduce the secreted VEGF protein in these cells, reflecting an unknown regulatory mechanism mediated by the BLU gene in NPC. Cells expressing BLU inhibited cellular invasion, migration and tube formation. These in vitro results were further confirmed by in vivo tumor suppression and a matrigel plug angiogenesis assay in nude mice. Tube-forming ability was clearly inhibited, when the BLU gene is expressed in these cells. Up to 70-90% of injected tumor cells expressing increased exogenous BLU underwent cell death in animal assays. Overexpressed BLU only inhibited VEGF165 expression in differentiated squamous NPC HK1 cells, but also showed an anti-angiogenic effect in the animal assay, revealing a complicated mechanism regulating angiogenesis and the microenvironment in different NPC cell lines. Results of these studies indicate that alteration of BLU gene expression influences anti-angiogenesis pathways and is important for the development of NPC.

SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

Visit-to-visit systolic blood pressure variability and outcomes in hemodialysis.

Visit-to-visit blood pressure variability (VTV-BPV) is an independent risk factor for cardiovascular events and death in the general population. We sought to determine the association of VTV-BPV with outcomes in patients on hemodialysis, using data from a National Institutes of Health-sponsored randomized trial (the HEMO study). We used the coefficient of variation (CV) and the average real variability in systolic blood pressure (SBP) as metrics of VTV-BPV. In all, 1844 out of 1846 randomized subjects had at least three visits with SBP measurements and were included in the analysis. Median follow-up was 2.5 years (interquartile range 1.3-4.3 years), during which time there were 869 deaths from any cause and 408 (adjudicated) cardiovascular deaths. The mean pre-dialysis SBP CV was 9.9 ± 4.6%. In unadjusted models, we found a 31% higher risk of death from any cause per 10% increase in VTV-BPV. This association was attenuated after multivariable adjustment but remained statistically significant. Similarly, we found a 28% higher risk of cardiovascular death per 10% increase in VTV-BPV, which was attenuated and no longer statistically significant in fully adjusted models. The associations among VTV-BPV, death and cardiovascular death were modified by baseline SBP. In a diverse, well-dialyzed cohort of patients on maintenance hemodialysis, VTV-BPV, assessed using metrics of variability in pre-dialysis SBP, was associated with a higher risk of all-cause mortality and a trend toward higher risk of cardiovascular mortality, particularly in patients with a lower baseline SBP.

Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma.

Fibulin-2 (FBLN2) has been identified as a candidate tumor-suppressor gene in nasopharyngeal carcinoma (NPC). Originally identified through a chromosome 3 NotI genomic microarray screen, it shows frequent deletion or methylation in NPC. FBLN2 is located on chromosome 3p25.1 and is associated with tumor development through its important interactions with the extracellular matrix (ECM) proteins. FBLN2 encodes two isoforms. The short isoform (FBLN2S) is expressed abundantly in normal tissues, but is dramatically downregulated in NPC, while the long isoform (FBLN2L) is either not detectable or is expressed only at low levels in both normal and tumor tissues. Reintroduction of this FBLN2S inhibited cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, in vivo studies in nude mice show its expression is associated with tumor and angiogenesis suppression. FBLN2-associated angiogenesis occurs via concomitant downregulation of vascular endothelial growth factor and matrix metalloproteinase 2. This study provides compelling evidence that FBLN2S has an important tumor-suppressive and anti-angiogenic role in NPC.

Leukogram abnormalities in gnotobiotic pigs infected with porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) is a single-stranded circular DNA virus that is the causative agent of porcine circovirus associated disease (PCVAD), a disease complex affecting swine around the world. Although this virus is believed to negatively affect the host's immune system, the mechanism by which PCV2 induces disease is not completely understood. This report describes a series of PCV2 experiments using the gnotobiotic pig model in which a relationship was demonstrated between abnormal leukograms and development of clinical disease in PCV2-infected pigs. When compared to control pigs the leukogram was characterized by a decrease in lymphocytes within 14 days post inoculation (dpi) followed by an increase in neutrophils 7-14 days later. No significant changes in the circulating monocyte, basophil, and eosinophil cell populations were detected. The combination of an absolute neutrophilia and lymphopenia produced a neutrophil/lymphocyte ratio that was predictive of clinical disease and was inversely correlated with the presence of neutralizing antibodies. Based on previous reports, the lymphopenia may be attributed to a direct cytolytic effect of the virus and could negatively affect the pig's immune response. The role of the neutrophilia in the pathogenesis of PCVAD in gnotobiotic pigs is unknown.

Postweaning multisystemic wasting syndrome produced in gnotobiotic pigs following exposure to various amounts of porcine circovirus type 2a or type 2b.

In late 2005, a postweaning, high mortality syndrome spread rapidly through finishing barns in swine dense areas of the United States. Diagnostic investigations consistently detected porcine circovirus type 2 (PCV2) from diseased tissues. Subsequent genetic analysis revealed that the infectious agent was a PCV2 type termed "PCV2b". Prior to late 2004, only the PCV2a type, but not PCV2b, had been reported in North America. In this communication, we produce severe postweaning multisystemic wasting syndrome (PMWS) in gnotobiotic pigs using infectious PCV2a and PCV2b generated from DNA clones constructed from field isolates identified in the 2005 outbreak. Clinical signs exhibited by diseased pigs included anorexia, dyspnea and listlessness. Mortality was typically observed within 12h of onset of dyspnea. The most striking microscopic lesions in affected animals were severe hepatic necrosis and depletion of germinal centers in lymph nodes with associated abundant PCV2 viral antigen. Clinical signs and lesions observed in these studies were comparable to those reported in experiments with gnotobiotic pigs inoculated with a PCV2a isolate while concurrently receiving immune-stimulation or co-infection with porcine parvovirus or torque teno virus. The animals in these studies were confirmed to be free of detectable porcine parvovirus, porcine reproductive and respiratory syndrome virus, bovine viral diarrhea virus, swine hepatitis E virus, and aerobic and anaerobic bacteria. Seven out of 24 PCV2 inoculated pigs had a detectable congenital torque teno virus infection with no correlation to clinical disease. Thus, in these studies, both PCV2a and PCV2b isolates were singularly capable of inducing high mortality in the absence of any detectable infectious co-factor.

Porcine bocaviruses: genetic analysis and prevalence in Chinese swine population.

In members of the Bocavirus genus, that contain three open reading frames (ORFs) of the Parvovirinae subfamily, porcine bocaviruses (PoBoVs) exhibit the most genetic diversity. Based on the ORF2-encoded viral protein (VP1) classification, the six reported porcine bocaviruses were grouped into four species: PoBoV1 (porcine boca-like virus or PBoLV), PoBoV2 (porcine parvovirus 4 or PPV4), PoBoV3 (PBoV1/PBoV2) and PoBoV4 (6V/7V), with PoBoV3 and PoBoV4 each having two genotype viruses. All four PoBoV species were detected in the 166 samples collected in 2010 from swine herds located in ten provinces of China. The detection rates for PoBoV1-4 were 28·9%, 6·6%, 19·3% and 39·7%, respectively. The co-infection combinations involving these six porcine bocaviruses in the collected samples were very complex. Furthermore, mixed infections with viruses from other families (porcine reproductive and respiratory syndrome virus, classic swine fever virus and porcine circovirus type 2) were also detected.

Systolic blood pressure and mortality in prevalent haemodialysis patients in the HEMO study.

Previous studies of blood pressure and mortality in haemodialysis have yielded mixed results, perhaps due to confounding by comorbid conditions. We hypothesized that after improved accounting for confounding factors, higher systolic blood pressure (SBP) would be associated with higher all-cause mortality. We conducted a secondary analysis of data from the haemodialysis study, a randomized trial in prevalent haemodialysis patients. We used three proportional hazard models to determine the relative hazard at different levels of SBP: (1) Model-BL used baseline SBP; (2) Model-TV used SBP as a time-varying variable; and (3) Model-TV-Lag added a 3-month lag to Model-TV to de-emphasize changes in SBP associated with acute illness. In all the models, pre-dialysis SBP <120 mm Hg was associated with a higher risk of mortality compared with the referent group (140-159 mm Hg); higher pre-dialysis SBP was not associated with higher risk of mortality. In conclusion, we observed a robust association between lower pre-dialysis SBP and higher risk for all-cause and cardiovascular mortality in a well-characterized cohort of prevalent haemodialysis patients. Randomized clinical trials are needed to define optimal blood pressure targets in the haemodialysis population.

Serum alkaline phosphatase and mortality in hemodialysis patients.

BACKGROUND: Alkaline phosphatase is typically considered as an innocent by-stander, but emerging data suggest that alkaline phosphatase might play a pathogenic role in vascular calcification and thus contribute to increased mortality in hemodialysis patients. STUDY DESIGN: Longitudinal analyses of the existing HEMO Study database. SETTING AND PARTICIPANTS: 1,827 HEMO Study participants. PREDICTOR: Serum alkaline phosphatase level. OUTCOME AND MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: Based on the median serum alkaline phosphatase of 97 IU/l, participants were divided into low (< 97 IU/l) and high (> or = 97 IU/l) serum alkaline phosphatase groups. The lower serum alkaline phosphatase group was associated with older age, male gender, non-black race and shorter dialysis years as well as higher serum calcium, higher serum calcium-phosphorus product and lower parathyroid hormone levels. Mean serum liver enzyme values were in the normal range in both groups, but the high alkaline phosphatase group had slightly higher values. In a multivariate time-dependent Cox model using baseline and follow-up values of serum alkaline phosphatase levels, adjusted for demographics, HEMO Study groups, comorbidity, bone metabolism parameters and liver enzymes, each doubling of serum alkaline phosphatase was significantly associated with increased hazard of all-cause (hazard ratio 1.44, 95% CI 1.30 - 1.59) and cardiovascular mortality (hazard ratio 1.35, 95% CI 1.16 - 1.57). LIMITATIONS: Nonstandardized measurements of alkaline phosphatase. CONCLUSIONS: Serum alkaline phosphatase is associated with increased mortality in hemodialysis patients, independent of bone metabolism parameters and liver enzymes. Alkaline phosphatase might be a potential therapeutic target in hemodialysis patients.

Improving general practitioners' interviewing skills in managing patients with depression and anxiety: a randomized controlled clinical trial.

BACKGROUND: Studies regarding the effectiveness of CME programmes on physicians' behaviour and communication skills showed inconsistent results. Few randomized controlled trials have been conducted in Asia. METHODS: To evaluate the effectiveness of a 4 2-hour education programme to improve GP interviewing behaviours, 16 general practitioners were randomized to the intervention and control groups, respectively. Physicians assigned to the intervention group received 8 hours of training emphasizing interviewing behaviours in the diagnosis and treatment of depression and generalized anxiety disorders (GDS). Those assigned to the control group did not receive any training until the completion of study. Standardized patients were used to evaluate the performance of physicians. Two consultations before and after enrolling in the education programme were videotaped. Independent evaluations of consultations were made by a trained clinical psychologist and a social worker blinded to the study status of physicians. The rating schedule for the videotapes was based on the tasks listed on the Calgary Cambridge Observation Guide. RESULTS: The change of score between the intervention and control physicians was significantly different in 'active listening and facilitating patients' response' (p = 0.011) with the intervention physicians having improvement of score. For 'non-verbals', 'understanding patient's perspective' and 'negotiating mutual plan of action', positive change of score in the intervention physicians were seen when compared to that of the control, although the difference did not reach statistical significance (p = 0.06, p = 0.05, p = 0.06, respectively). However, for 'opening', 'structuring the consultation', 'explanation and planning' and 'closure', there were no statistical significant differences between control and intervention group. CONCLUSIONS: Our results showed that only certain communication skills, such as active listening and facilitating patient's response, can be taught in the management of depression and generalized anxiety disorder (GAD) in Chinese primary care physicians.

Homologous recombination plays minor role in excision of unit-length viral genomes from head-to-tail direct tandem repeats of porcine circovirus during DNA replication in Escherichia coli.

In this report, we confirmed previous work that a theta-replicating bacterial plasmid containing 1.75 copies of genomic porcine circovirus (PCV) DNA in head-to-tail tandem (HTT) [a partial copy of PCV type 1 (PCV1), a complete copy of PCV type 2 (PCV2) and two origins of DNA replication (Ori)] yielded three different double-stranded DNA species when transformed into Escherichia coli: the input construct (U), the unit-length PCV1/PCV2 genome with a composite Ori lacking the plasmid vector (Q(RC)) and the remaining left-over 0.75 copy PCV1/PCV2 genome with a different composite Ori inserted in the plasmid vector (L(RC)). Replication of U was presumably via the theta-like replication mechanism utilizing the colicin E1 Ori, while derivation of L(RC) and Q(RC) was via the rolling-circle replication (RCR) copy-release mechanism and required the presence of two PCV Oris and the virus-encoded Rep protein. Essentially, excision of a unit-length PCV1/PCV2 genome (Q(RC)) via RCR from U yielded L(RC). Furthermore, we examined whether homologous recombination may also result in excision of a different type of unit-length PCV genome (Q(H)) from identical HTT constructs to generate L(H). Whereas the generation of L(RC) is Rep-protein-dependent, the generation of L(H) is Rep-protein-independent. Accordingly, the L(RC) and Q(RC) molecules derived from RCR possess different characteristics from the L(H) and Q(H) molecules generated via homologous recombination. In one of the studies in which both L(RC) and L(H) were generated simultaneously from the same HTT construct, out of 69 samples analyzed, 66 were derived via RCR and 3 were derived via homologous recombination. Thus, in comparison with RCR, homologous recombination plays a minor role in the excision of unit-length PCV genomes from HTT constructs in Escherichia coli.

Generation and characterization of sodium-dicarboxylate cotransporter-deficient mice.

The sodium-dependent dicarboxylate cotransporter (NaDC1) has a proposed function of reabsorbing various Krebs cycle intermediates in the kidney and the small intestine. Since Krebs cycle intermediates have been suggested to be important for renal cell survival and recovery after hypoxia and reoxygenation, the transporter may play a role in the recovery of the kidney. Additionally, mutations in the transporter homolog in Drosophila led to fly longevity which was thought to be similar to that induced by caloric restriction (CR). To clarify the role of the sodium dicarboxylate cotransporter in vivo we generated cotransporter-deficient mice. These knockout mice excreted significantly higher amounts of various Krebs cycle intermediates in their urine; thus confirming the proposed function to reabsorb these metabolic intermediates in the kidney. No other phenotypic change was identified in these mice, however. Transporter deficiency did not affect renal function under normal physiological conditions, nor did it have an effect on renal damage and recovery from ischemic injury. Additionally, the absence of the transporter did not lead to metabolic or physiological changes associated with CR. Our results suggest that although the sodium dicarboxylate cotransporter is involved in regulating levels of various Krebs cycle intermediates in the kidney, impaired uptake of these intermediates does not significantly affect renal function under normal or ischemic stress.

Detection of two porcine circovirus type 2 genotypic groups in United States swine herds.

In late 2005, sporadic cases of an acute onset disease of high mortality were observed in 10- to 16-week-old growing pigs among several swine herds of the United States. Tissues from the affected pigs in Kansas, Iowa, and North Carolina were examined, and porcine circovirus type 2 (PCV2) was detected consistently among these tissues. Phylogenetically, PCV2 can be divided into two major genotypic groups, PCV2-group 1 and PCV2-group 2. Whereas PCV2-group 1 isolates were detected in all the diseased animals, only two of the diseased animals harbored PCV2-group 2 isolates. This observation is important because PCV2-group 1 isolates had never been reported in the United States before (GenBank as of May 16, 2006), and they are closely related to the PCV2-group 1 isolates that have been described in Europe and Asia, previously. Our analysis revealed that each genotypic group contains a distinct stretch of nucleotide or amino acid sequence that may serve as a signature motif for PCV2-group 1 or PCV2-group 2 isolates.

Efficacy of local dipyridamole therapy in a porcine model of arteriovenous graft stenosis.

Perivascular delivery of antiproliferative drugs has been proposed as an approach to prevent neointimal hyperplasia associated with hemodialysis polytetrafluoroethylene (PTFE) grafts. We examined this approach to deliver dipyridamole in a porcine graft model. PTFE grafts were implanted between the carotid artery and external jugular vein bilaterally in pigs. During the surgery or 1 week post-graft placement, dipyridamole (0.26-52 mg) alone or incorporated in microspheres was mixed with an injectable polymeric gel and applied to the graft-arterial and graft-venous anastomoses on one side, whereas the contralateral control graft received no treatment. Three or four weeks after operation, the grafts and adjacent vessels were explanted en bloc and cross-sections of the anastomoses were examined histologically. The degree of neointimal hyperplasia was quantified by planimetry. In separate experiments, dipyridamole was extracted from the explanted tissues and assayed by spectrofluorometry. The normalized median hyperplasia areas of the treated and control graft-venous anastomoses were 0.45 (25th-75th percentile, 0.30-0.86) and 0.24 (0.21-0.30), respectively (N=7; P=0.08). The median hyperplasia areas of the treated and control graft-arterial anastomoses were 0.12 (0.07-0.39) and 0.11 (0.09-0.13), respectively (N=7; P=0.31). The dipyridamole levels in the vascular walls around the anastomoses were at or above the in vitro inhibitory concentrations for approximately 3 weeks. These results suggest that the local perivascular sustained delivery of dipyridamole, even at high dosages, was ineffective in inhibiting neointimal hyperplasia associated with PTFE grafts in a porcine model.