The effect of bitewing radiography on estimates of dental caries experience among children differs according to their disease experience.

BACKGROUND: Radiography is a regularly used and accepted adjunct to visual examination in the diagnosis of dental caries. It is assumed that not using radiographs can lead to underestimation of dental caries experience with most reports having involved studies of young adults or adolescents, and been focused on the permanent dentition. The aim of this study was to determine the relative contributions of bitewing radiography and clinical examination in the detection of dental caries in primary molars and to determine whether those contributions differ according to caries experience. METHODS: A cross-sectional study was conducted, involving examinations undertaken in dental clinics. Bitewing radiographs taken at the time of the clinical examination were developed and read later, with the data from those used at the analysis stage to adjust the caries diagnosis for the mesial, occlusal and distal surfaces of the primary molar teeth. Children's clinically determined dmfs score was used to allocate them to one of three caries experience groups (0 dmfs, 1-8 dmfs, or 9+ dmfs). RESULTS: Of the 501 three-to-eight-year-old children examined, nearly three-quarters were younger than six. Caries prevalence and mean dmfs after clinical examination alone and following radiographs were 63.1% and 4.6 (sd, 6.2), and 74.7% and 5.8 (sd, 6.5) respectively. Among children with a dmfs of 1-8, the number of lesions missed during the clinical examination was greater than the number of 106 (25.6%) in children with a dmfs of 9+. In the 185 children with no apparent caries at clinical examination, 124 lesions were detected radiographically, among 58 (46.8%) of those. CONCLUSIONS: Taking bitewing radiographs in young children is not without challenges or risks, and it must be undertaken with these in mind. Diagnostic yields from bitewing radiographs are greater for children with greater caries experience. The findings of this study further support the need to consider using bitewing radiographs in young children to enhance the management of lesions not detected by a simple visual examination alone. TRIAL REGISTRATION: ACTRN12614000844640 .

Measuring acute postoperative pain using the visual analog scale: the minimal clinically important difference and patient acceptable symptom state.

Background: The 100 mm visual analog scale (VAS) score is widely used to measure pain intensity after surgery. Despite this widespread use, it is unclear what constitutes the minimal clinically important difference (MCID); that is, what minimal change in score would indicate a meaningful change in a patient's pain status. Methods: We enrolled a sequential, unselected cohort of patients recovering from surgery and used a VAS to quantify pain intensity. We compared changes in the VAS with a global rating-of-change questionnaire using an anchor-based method and three distribution-based methods (0.3 sd , standard error of the measurement, and 5% range). We then averaged the change estimates to determine the MCID for the pain VAS. The patient acceptable symptom state (PASS) was defined as the 25th centile of the VAS corresponding to a positive patient response to having made a good recovery from surgery. Results: We enrolled 224 patients at the first postoperative visit, and 219 of these were available for a second interview. The VAS scores improved significantly between the first two interviews. Triangulation of distribution and anchor-based methods resulted in an MCID of 9.9 for the pain VAS, and a PASS of 33. Conclusions: Analgesic interventions that provide a change of 10 for the 100 mm pain VAS signify a clinically important improvement or deterioration, and a VAS of 33 or less signifies acceptable pain control (i.e. a responder), after surgery.

A randomised controlled trial of peri-operative pregabalin vs. placebo for video-assisted thoracoscopic surgery.

We allocated 52 participants to oral pregabalin 300 mg and 48 participants to placebo tablets before thoracoscopic surgery and for five postoperative days. The median (IQR [range]) cumulative pain scores at rest for nine postoperative months were 184 (94-274 [51-1454]) after pregabalin and 166 (66-266 [48-1628]) after placebo, p = 0.39. The corresponding scores on deep breathing were 468 (281-655 [87-2870]) and 347 (133-561 [52-3666]), respectively, p = 0.16. After three postoperative months, 29/100 participants had persistent surgical site pain, 19/52 after pregabalin and 10/48 after placebo, p = 0.12, of whom four and five, respectively, attended a pain management clinic, p = 0.24. The median (IQR [range]) morphine equivalent consumption six days after surgery was 273 (128-619 [39-2243]) mg after pregabalin and 319 (190-663 [47-2258]) mg after placebo, p = 0.35.

Serratia marcescens harbouring SME-type class A carbapenemases in Canada and the presence of blaSME on a novel genomic island, SmarGI1-1.

OBJECTIVES: An increasing prevalence since 2010 of Serratia marcescens harbouring the Ambler class A carbapenemase SME prompted us to further characterize these isolates. METHODS: Isolates harbouring bla(SME) were identified by PCR and sequencing. Phenotypic analysis for carbapenemase activity was carried out by a modified Hodge test and a modified Carba NP test. Antimicrobial susceptibilities were determined by Etest and Vitek 2. Typing was by PFGE of macrorestriction digests. Whole-genome sequencing of three isolates was carried out to characterize the genomic region harbouring the bla(SME)-type genes. RESULTS: All S. marcescens harbouring SME-type enzymes could be detected using a modified Carba NP test. Isolates harbouring bla(SME) were resistant to penicillins and carbapenems, but remained susceptible to third-generation cephalosporins, as well as fluoroquinolones and trimethoprim/sulfamethoxazole. Isolates exhibited diverse genetic backgrounds, though 57% of isolates were found in three clusters. Analysis of whole-genome sequence data from three isolates revealed that the bla(SME) gene occurred in a novel cryptic prophage genomic island, SmarGI1-1. CONCLUSIONS: There has been an increasing occurrence of S. marcescens harbouring bla(SME) in Canada since 2010. The bla(SME) gene was found on a genomic island, SmarGI1-1, that can be excised and circularized, which probably contributes to its dissemination amongst S. marcescens.

Complete sequences of a novel blaNDM-1-harbouring plasmid from Providencia rettgeri and an FII-type plasmid from Klebsiella pneumoniae identified in Canada.

OBJECTIVES: Emergence of plasmids harbouring bla(NDM-1) is a major public health concern due to their association with multidrug resistance and their potential mobility. METHODS: PCR was used to detect bla(NDM-1) from clinical isolates of Providencia rettgeri (PR) and Klebsiella pneumoniae (KP). Antimicrobial susceptibilities were determined using Vitek 2. The complete DNA sequence of two bla(NDM-1) plasmids (pPrY2001 and pKp11-42) was obtained using a 454-Genome Sequencer FLX. Contig assembly and gap closures were confirmed by PCR-based sequencing. Comparative analysis was done using BLASTn and BLASTp algorithms. RESULTS: Both clinical isolates were resistant to all ß-lactams, carbapenems, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole, and susceptible to tigecycline. Plasmid pPrY2001 (113 295 bp) was isolated from PR. It did not show significant homology to any known plasmid backbone and contained a truncated repA and novel repB. Two bla(NDM-1)-harbouring plasmids from Acinetobacter lwoffii (JQ001791 and JQ060896) shared 100% similarity to a 15 kb region that contained bla(NDM-1). pPrY2001 also contained a type II toxin/antitoxin system. pKp11-42 (146 695 bp) was isolated from KP. It contained multiple repA genes. The plasmid backbone had the highest homology to the IncFIIk plasmid type (51% coverage, 100% nucleotide identity). The bla(NDM-1) region was unique in that it was flanked upstream by IS3000 and downstream by a novel transposon designated Tn6229. pKp11-42 also contained a number of mutagenesis and plasmid stability proteins. CONCLUSIONS: pPrY2001 differed from all known plasmids due to its novel backbone and repB. pKp11-42 was similar to IncFIIk plasmids and contained a number of genes that aid in plasmid persistence.

Mutagenicity and tumorigenicity of the four enantiopure bay-region 3,4-diol-1,2-epoxide isomers of dibenz[a,h]anthracene.

Each enantiomer of the diastereomeric pair of bay-region dibenz[a,h]anthracene 3,4-diol-1,2-epoxides in which the benzylic 4-hydroxyl group and epoxide oxygen are either cis (isomer 1) or trans (isomer 2) were evaluated for mutagenic activity. In strains TA 98 and TA 100 of Salmonella typhimurium, the diol epoxide with (1S,2R,3S,4R) absolute configuration [(-)-diol epoxide-1] had the highest mutagenic activity. In Chinese hamster V-79 cells, the diol epoxide with (1R,2S,3S,4R) absolute configuration [(+)-diol epoxide-2] had the highest mutagenic activity. The (1R,2S,3R,4S) diol epoxide [(+)-diol epoxide-1] also had appreciable activity, whereas the other two bay-region diol epoxide enantiomers had very low activity. In tumor studies, the (1R,2S,3S,4R) enantiomer was the only diol epoxide isomer tested that had strong activity as a tumor initiator on mouse skin and in causing lung and liver tumors when injected into newborn mice. This stereoisomer was about one-third as active as the parent hydrocarbon, dibenz[a,h]anthracene as a tumor initiator on mouse skin; it was several-fold more active than dibenz[a,h]anthracene as a lung and liver carcinogen when injected into newborn mice. (-)-(3R,4R)-3ß,4α-dihydroxy-3,4-dihydro-dibenz[a,h]anthracene [(-)-3,4-dihydrodiol] was slightly more active than dibenz[a,h]anthracene as a tumor initiator on mouse skin, whereas (+)-(3S,4S)-3α,4ß-dihydroxy-3,4-dihydro-dibenz[a,h]anthracene [(+)-3,4-dihydrodiol] had only very weak activity. The present investigation and previous studies with the corresponding four possible enantiopure bay-region diol epoxide enantiomers/diastereomers of benzo[a]pyrene, benz[a]anthracene, chrysene, benzo[c]phenanthrene, dibenz[c,h]acridine, dibenz[a,h]acridine and dibenz[a,h]anthracene indicate that the bay-region diol epoxide enantiomer with [R,S,S,R] absolute stereochemistry has high tumorigenic activity on mouse skin and in newborn mice.

The VanE operon in Enterococcus faecalis N00-410 is found on a putative integrative and conjugative element, Tn6202.

OBJECTIVES: To date no complete genetic structure of acquired DNA harbouring a d-Ala-d-Ser operon in an Enterococcus is known. We wished to characterize the acquired DNA harbouring the vanE operon located in the Enterococcus faecalis N00-410 chromosome. METHODS: Whole genome sequencing of E. faecalis N00-410 was conducted by massively parallel sequencing. Two sequence contigs harbouring the vanE region were linked by PCR and the acquired DNA harbouring the vanE operon was completely characterized. Excision/integration of the region was determined by PCR and transfer attempted by conjugation. RESULTS: The regions flanking the vanE operon were analysed and a total of 42 open reading frames were identified in a region flanked by inverted terminal and direct repeats (Tn6202). Tn6202 could be excised from the chromosome, circularized and the target site rejoined, but transfer could not be demonstrated. CONCLUSIONS: The vanE operon was found on the putative integrative and conjugative element Tn6202 in the E. faecalis N00-410 chromosome. This represents the first characterization of acquired DNA harbouring a D-Ala-D-Ser operon.

A case report of Lemierre's Syndrome associated with dental sepsis.

INTRODUCTION: Lemierre's syndrome is a potentially fatal condition characterised by spread of an oropharyngeal infection, resulting in thrombosis of the internal jugular vein. This leads to septicaemia and possible metastatic abscesses. CASE PRESENTATION: We discuss the case of a previously healthy 17-year-old male who developed Lemierre's syndrome following dental sepsis. He presented with bilateral submandibular and submental swelling extending into the neck and chest. His management included a tracheostomy; incision and drainage of the abscesses; drainage of a pleural effusion and prolonged anticoagulant therapy. CONCLUSION: The incidence of Lemierre's disease appears to be increasing and early diagnosis is essential. A high index of suspicion is needed in cases of oropharyngeal infection followed by fever, tender swelling of the neck and dysphagia - especially in young patients.

Carbapenem-resistant Gram-negative bacilli in Canada 2009-10: results from the Canadian Nosocomial Infection Surveillance Program (CNISP).

OBJECTIVES: To investigate the occurrence and molecular mechanisms associated with carbapenemases in carbapenem-resistant Gram-negative isolates from Canadian cases. METHODS: Twenty hospital sites across Canada submitted isolates for a 1 year period starting 1 September 2009. All Enterobacteriaceae with MICs ≥ 2 mg/L and Acinetobacter baumannii and Pseudomonas aeruginosa with MICs ≥ 16 mg/L of carbapenems were submitted to the National Microbiology Laboratory (NML) where carbapenem MICs were confirmed by Etest and isolates were characterized by PCR for carbapenemase genes, antimicrobial susceptibilities, PFGE and plasmid isolation. RESULTS: A total of 444 isolates (298 P. aeruginosa, 134 Enterobacteriaceae and 12 A. baumannii) were submitted to the NML of which 274 (61.7%; 206 P. aeruginosa, 59 Enterobacteriaceae and 9 A. baumannii) met the inclusion criteria as determined by Etest. Carbapenemase genes were identified in 30 isolates: bla(GES-5) (n = 3; P. aeruginosa), bla(KPC-3) (n = 7; Enterobacteriaceae), bla(NDM-1) (n = 2; Enterobacteriaceae), bla(VIM-2) and bla(VIM-4) (n = 8; P. aeruginosa) bla(SME-2) (n = 1; Enterobacteriaceae) and bla(OXA-23) (n = m9; A. baumannii). PFGE identified a cluster in each of Enterobacteriaceae, P. aeruginosa and A. baumannii corresponding to isolates harbouring carbapenemase genes. Three KPC plasmid patterns (IncN and FllA) were identified where indistinguishable plasmid patterns were identified in unrelated clinical isolates. CONCLUSIONS: Carbapenemases were rare at the time of this study. Dissemination of carbapenemases was due to both dominant clones and common plasmid backbones.

Evaluation of developmentally hypomineralised enamel after surface pretreatment with Papacarie Duo gel and different etching modes: an in vitro SEM and AFM study.

PURPOSE: This study aimed at investigating the surface morphology and nanotopography of normal enamel (NE) and developmentally hypomineralised enamel (HE) when subjected to various pretreatment protocols under scanning electron microscopy (SEM) and atomic force microscopy (AFM). METHODS: Sixteen NE, 16 creamy/white (CW) HE and 16 yellow/brown (YB) HE specimens sectioned from extracted hypomineralised first permanent molars (FPMs) were included in this study. They were randomly distributed into 12 experimental groups (n = 4). Each group involved the following: (1) deproteinisation with Papacarie Duo® gel or no deproteinisation, and (2) the use of Scotchbond™ Universal Adhesive (Scotchbond) in self-etch (SE) mode or 37% phosphoric acid etchant. Subsequently, the surface morphology and nanotopography of pretreated enamel specimens were evaluated under SEM and AFM, respectively. RESULTS: SEM observation showed that deproteinisation with Papacarie Duo® gel before phosphoric acid etching led to favourable etching patterns. This was consistent across all groups irrespective of the type of enamel specimen and the severity of hypomineralisation. In contrast, AFM results identified three factors that influenced surface parameters: (1) type of enamel specimen, (2) severity of hypomineralisation and (3) etching mode. YB HE recorded higher surface roughness values than CW HE and NE when subjected to the same pretreatment protocol. Deproteinisation and the application of Scotchbond in SE mode led to minimal topographic changes; however, acid etching was associated with an increase in surface roughness. CONCLUSION: Deproteinisation with Papacarie Duo® gel followed by acid etching contributed to improved etching patterns on HE.

Plasmid comparison and molecular analysis of Klebsiella pneumoniae harbouring bla(KPC) from New York City and Toronto.

OBJECTIVES: This study examined Klebsiella pneumoniae clinical isolates and their bla(KPC) plasmids to determine potential relatedness of the isolates and their plasmids harbouring carbapenem resistance mechanisms. METHODS: K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae from New York City (NYC) (n = 19) and Toronto (n = 2) were typed by PFGE and multilocus sequence typing (MLST). bla(KPC)-harbouring plasmids were transformed into Escherichia coli DH10B(TM), restricted using EcoRI and analysed for bla content and replicon (rep) type. Susceptibility profiles for clinical and transformed strains were determined by automated microbroth dilution using CLSI breakpoints. Outer membrane protein (OMP) genes were analysed by sequencing of ompk35 and ompk36. RESULTS: PFGE analysis identified 17 related strains (≥ 80% similarity; 11 KPC-2, 6 KPC-3) where ST258 was the dominant clonal type. All clinical isolates contained both bla(SHV) and bla(TEM-1) and, with the exception of one isolate, were multidrug resistant (MDR). Transformed KPC plasmids (n = 21) carried TEM-1 (n = 18) and were MDR (n = 5). Three plasmid clusters, repFIIA (n = 10), repR (n = 3) and an unknown type (n = 3), were observed. repFllA plasmids were observed from both NYC and Toronto strains. OMP gene analysis revealed premature stop codons in ompk35 and numerous deletions and insertions in ompk36. CONCLUSIONS: The dissemination of bla(KPC) is due both to carriage of similar KPC-harbouring plasmids within genetically distinct K. pneumoniae and to clonal spread of K. pneumoniae with unrelated KPC plasmids.

Composition-property relationships for an experimental composite nerve guidance conduit: evaluating cytotoxicity and initial tensile strength.

The objective of this work was to examine the main (individual), combined (interaction) and second-order (quadratic) effects of: (i) poly(D,L-lactide-co-glycolide) (PLGA), (ii) F127, and (iii) a zinc-silicate based bioactive glass, on the cytotoxicity and ultimate tensile strength of an experimental nerve guidance conduit (NGC). The experimental plan was carried out according to a Box-Behnken design matrix. The effects of each compositional factor were quantified using response surface methodology (RSM) techniques. Linear and quadratic polynomial equations were developed to examine cytotoxicity (after incubation at 3, 7 and 28 days) and initial ultimate tensile strength (UTS(0)). Multiple regression analyses showed that the developed models yielded a good prediction for each response examined. It was observed that the beneficial effects of PLGA and bioactive glass on controlling cytotoxicity appeared greater than that of F127. Furthermore, the experimental conduits (with the exception of CNGC-I and CNGC-K) generally showed superior cytocompatibility when compared with the comparable literature for the clinically used nerve guidance conduit Neurolac(®). In this investigation, optimal compositions for cell viability were obtained for the following composition: PLGA = 18.89 wt%/F127 = 0.52 wt%/glass = 12.71 wt%. The optimization of composition with respect to ultimate tensile strength was also established (desired UTS(0) being based on the properties of the control device Neurolac(®) whose UTS is c.20 MPa). The desired UTS(0) of ≤ 20 MPa was found for the composition: PLGA = 18.63 wt%/F127 = 0.77 wt%/glass = 5.54 wt%. A UTS(0) ≤ 30 MPa was recorded for the composition: PLGA = 18.34 wt%/F127 = 0.62 wt%/glass = 9.83 wt%, such tensile strengths are comparable to, reported values for Neurolac(®). Examination of the composition-property relationships with respect to combining cell viability and UTS(0) indicated preferred compositions in the range 17.97-19.90 wt% PLGA, 0.16-1.13 wt% F127 and between 5.54 and ≤ 20 wt% glass. This research demonstrates the value of a design of experiments approach for the design of novel nerve guidance conduits, and shows that the materials examined may have potential for the repair of peripheral nerve discontinuities.

Hypoglycemia after accidental pediatric sulfonylurea ingestions.

BACKGROUND: Because the prevalence of type 2 diabetes increases annually, there has been an increase in pediatric exposures to sulfonylureas. These medications are associated with delayed and often prolonged hypoglycemia. As such, most authorities but not all recommend admission for all pediatric patients with an accidental sulfonylurea ingestion. METHODS: This study is a retrospective chart review of all pediatric patients with sulfonylurea exposures admitted for 9 years at an urban, pediatric teaching hospital. The incidence and characteristics of the hypoglycemia were recorded and analyzed. RESULTS: During this time span, 93 patients with accidental sulfonylurea exposures were admitted, with a median age of 1.83 years. Glyburide and glipizide accounted for most sulfonylureas. Hypoglycemia (blood glucose level <50 mg/dL) developed in 25 (58.1%) of 43 patients who ingested glipizide, compared with 10 (25.6%) of 39 patients who ingested glyburide. The overall incidence of hypoglycemia was 44%. Hypoglycemia was more likely to occur with glipizide ingestion than glyburide (odds ratio, 3.89 [95% confidence interval, 1.51-9.98]). No patient with a known time of ingestion developed hypoglycemia after 13 hours. CONCLUSIONS: Hypoglycemia is common after accidental sulfonylurea exposures. The results of this study support mandatory admission to a monitored setting for at least 16 hours, with frequent glucose determinations.

Atrial fibrillation: an approach to diagnosis and management in the emergency department.

Atrial fibrillation is the most common dysrhythmia encountered in the emergency department. In patients aged >65 years, the incidence approaches 10%, and the number of patients with atrial fibrillation is expected to almost double in the next 30 years. Atrial fibrillation and its associated comorbidities also carry significant healthcare cost. Electrocardiogram findings may be subtle at times, but prompt diagnosis is needed to maximize good outcomes, especially when patients are cardiovascularly compromised. This review includes evidence-based recommendations on rate versus rhythm control, discusses pharmacologic versus electrical cardioversion, evaluates thromboembolic risk, and provides options for anticoagulation.

A Primary Care Randomized Controlled Trial of Hall and Conventional Restorative Techniques.

OBJECTIVES: To investigate treatment outcomes of different restorative techniques undertaken by dental therapists for primary molar carious lesions in a sample of children in New Zealand primary care. METHODS: This was a randomized controlled trial with children aged 3 to 8 y in New Zealand's Whanganui region. Children meeting inclusion criteria were randomly allocated to treatment with either the Hall technique (HT), in which a stainless-steel crown (SSC) is placed without any carious tissue removal or tooth preparation, or a non-Hall conventional restorative approach (NHT), including tooth preparation with selective carious tissue removal; this included SSC, amalgam, composite, or glass ionomer cement (GIC) restorations. Restorative outcomes after 12 and 24 mo were categorized as success, minor failure, or major failure. RESULTS: Of the 295 eligible children, 149 and 146 were allocated to the HT and NHT groups, respectively, with a total of 570 carious primary molars treated by 13 dental therapists. The participant follow-up rates at 12 and 24 mo were 95% and 91%. SSCs were the most commonly used restoration in the NHT group (60%), followed by GIC (28%). SSCs were the most successful restorations regardless of whether they were placed with the HT or NHT, with success rates of 89% and 92% at 12 mo and 85% and 86% at 24 mo. In the NHT group, the treatment material was a predictor of minor failure at 12 and 24 mo, with significantly more failures with GICs. CONCLUSIONS: SSCs placed by dental therapists are a highly successful restoration for the primary dentition, regardless of whether they are placed with the HT or conventionally. The high failure rate of glass ionomer restorations means that they cannot be recommended for widespread use in New Zealand primary care (Australian New Zealand Clinical Trials Registry, ACTRN12614000844640). KNOWLEDGE TRANSFER STATEMENT: The findings of this study can be used by policy makers and clinicians when deciding on which materials and which approach to use to maximize success and to minimize retreatment rates when providing restorative treatment for carious primary molars in children's primary oral health care. Results also suggest that undertaking research in the primary care setting may enhance translation of new knowledge and techniques into clinicians' hands.

Gender-based Barriers to the Advancement of Women in Academic Emergency Medicine: A Multi-Institutional Survey Study.

INTRODUCTION: Leadership positions occupied by women within academic emergency medicine have remained stagnant despite increasing numbers of women with faculty appointments. We distributed a multi-institutional survey to women faculty and residents to evaluate categorical characteristics contributing to success and differences between the two groups. METHODS: An institutional review board-approved electronic survey was distributed to women faculty and residents at eight institutions and were completed anonymously. We created survey questions to assess multiple categories: determination; resiliency; career support and obstacles; career aspiration; and gender discrimination. Most questions used a Likert five-point scale. Responses for each question and category were averaged and deemed significant if the average was greater than or equal to 4 in the affirmative, or less than or equal to 2 in the negative. We calculated proportions for binary questions. RESULTS: The overall response rate was 55.23% (95/172). The faculty response rate was 54.1% (59/109) and residents' response rate was 57.1% (36/63). Significant levels of resiliency were reported, with a mean score of 4.02. Childbearing and rearing were not significant barriers overall but were more commonly reported as barriers for faculty over residents (P <0.001). Obstacles reported included a lack of confidence during work-related negotiations and insufficient research experience. Notably, 68.4% (65/95) of respondents experienced gender discrimination and 9.5% (9/95) reported at least one encounter of sexual assault by a colleague or supervisor during their career. CONCLUSION: Targeted interventions to promote female leadership in academic emergency medicine include coaching on negotiation skills, improved resources and mentorship to support research, and enforcement of safe work environments. Female emergency physician resiliency is high and not a barrier to career advancement.

Histidine-rich glycoprotein inhibits the antiproliferative effect of heparin on smooth muscle cells.

Histidine-rich glycoprotein (HRGP), an alpha-glycoprotein in human plasma that is also present in platelets and macrophages, binds heparin with high affinity and neutralizes its anticoagulant activity. We now report that HRGP specifically inhibits the antiproliferative effect of heparin on arterial smooth muscle cells while other heparinoid-binding proteins do not influence mitogenesis. The multicellular inflammatory response to endothelial injury characterized, in part, by the influx of platelets and macrophages, may be associated with HRGP release into the arterial microenvironment. This release of HRGP may allow smooth muscle cell proliferation and atherogenesis by inhibiting the action of endothelial cell-derived heparinoid substances.