Larger-scale feasibility trial of the families moving forward (FMF) connect mobile health intervention for caregivers raising children with fetal alcohol spectrum disorders.

Objective: Caregivers raising children with fetal alcohol spectrum disorders (FASD) have limited access to evidence-based supports. This single-arm feasibility trial assesses the Families Moving Forward (FMF) Connect app to determine readiness for a larger randomized controlled trial (RCT). Methods: Eligibility for this online trial included caregivers of children (ages 3-12) with FASD residing in the United States. Caregivers received FMF Connect for 12 weeks on their personal smartphones (iOS or Android). Pre- and post-assessments included child behavior, parenting and family functioning, and app quality; user experience interviews were conducted post-intervention. Usage and crashes were monitored. Study objectives assessed feasibility of the trial (recruitment, attrition, measure sensitivity), intervention (technical functionality, acceptability), and implementation (caregiver usage). Results: Recruitment strategies proved sufficient with 171 caregivers screened and 105 deemed eligible. Analyses identified a few predictive demographic and outcome variables related to attrition. Several study measures were sensitive to change. Additional trial and measurement improvements were identified. From a technological perspective, the FMF Connect app was functional; the Android prototype required more.

Adapting a measure of gross motor skills for individuals with CDKL5 deficiency disorder: A psychometric study.

PURPOSE: Validated measures capable of demonstrating meaningful interventional change in the CDKL5 deficiency disorder (CDD) are lacking. The study objective was to modify the Rett Syndrome Gross Motor Scale (RSGMS) and evaluate its psychometric properties for individuals with CDD. METHODS: Item and scoring categories of the RSGMS were modified. Caregivers registered with the International CDKL5 Clinical Research Network uploaded motor videos filmed at home to a protected server and completed a feedback questionnaire (n = 70). Rasch (n = 137), known groups (n = 109), and intra- and inter-rater reliability analyses (n = 50) were conducted. RESULTS: The age of individuals with CDD ranged from 1.5 to 34.1 years. The modified scale, Gross Motor-Complex Disability (GM-CD), comprised 17 items. There were no floor or ceiling effects and inter- and intra-rater reliability were good. Rasch analysis demonstrated that the items encompassed a large range of performance difficulty, although there was some item redundancy and some disordered categories. One item, Prone Head Position, was a poor fit. Caregiver-reported acceptability was positive. Scores differed by age and functional abilities. SUMMARY: GM-CD appears to be a suitable remotely administered measure and psychometrically sound for individuals with CDD. This study provides the foundation to propose the use of GM-CD in CDD clinical trials. Longitudinal evaluation is planned.

Outcomes and interventions in patients transported to hospital with ongoing CPR after out-of-hospital cardiac arrest - An observational study.

INTRODUCTION: The main objective was to present characteristics and outcome of patients without sustained field return of spontaneous circulation (ROSC) transported to hospital with ongoing cardiopulmonary resuscitation (CPR). Our secondary objectives were to investigate hospital-based interventions and the performance of the universal Termination of Resuscitation-rule (uTOR). METHODS: In this retrospective observational cohort study, out-of-hospital cardiac arrest (OHCA) patients arriving to the emergency department of a university hospital in Sweden during a six-year period (2010-2015) were identified using a prospectively recorded hospital-based registry. Additional data were retrieved from medical records and from the Swedish cardiopulmonary resuscitation registry. RESULTS: Among 409 patients transported with ongoing CPR, 7 survived to hospital discharge (1.7%). Hospital-based interventions against a suspected cause of arrest were attempted during ongoing resuscitation in 34 patients (8.3%), of whom 3 survived to hospital discharge. The remaining 4 survivors had spontaneous in-hospital ROSC. Survivors presented with either a shockable rhythm (n = 4) or pulseless electrical activity (n = 3). The uTOR identified non-survivors with a positive predictive value (PPV) of 98.4% and a specificity of 71.4% for termination. CONCLUSION: Survival after OHCA where sustained prehospital ROSC is not achieved is rare and available in-hospital interventions are rarely utilised. No patient with asystole as the first recorded rhythm survived. The uTOR identified non-survivors with a PPV of 98.4% but showed poor specificity.

Postoperative Cataract Endophthalmitis Masquerading as Hemorrhagic Occlusive Retinal Vasculitis (HORV): A Case Report.

Purpose: To report a case of postoperative cataract bacterial endophthalmitis masquerading as hemorrhagic occlusive retinal vasculitis (HORV).Case Report: A 69-year-old female presents following uncomplicated cataract surgery of her right eye with new onset floaters, aching pain, decreased visual acuity, increased intraocular pressure, deep anterior chamber reaction, vitritis, and retinal vascular sheathing with diffuse blot hemorrhages. The majority of these clinical symptoms are commonly seen in bacterial endophthalmitis with exception to the retinal findings, which point to possible diagnosis of HORV, a recently described, largely untreatable phenomena associated with intracameral vancomycin use during surgery. After careful investigation and examination, our patient was successfully treated with pars plana vitrectomy and intravitreal antibiotics.Conclusion: This case report describes the unusual case of a postoperative bacterial endophthalmitis presenting with characteristic signs of HORV, a largely untreatable, exceedingly rare phenomena that commonly results in poor visual acuity.

Root and Stem Rot of Begonia Caused by Phytopythium helicoides in Virginia.

In the summer of 2011, severe root and stem rot of begonia (Begonia × semperflorens-cultorum cv. Vodka Dark Red) was observed during a field trial. Seventy-eight percent of the plants had symptoms included foliar blight, blackened and rotting roots, rotting stems, and collapsing crown, often leading to plant death. Isolation from the diseased plant roots consistently recovered a Pythium-like species and 41 isolates were subcultured for identification. These isolates produced very similar single-strand conformation polymorphism (SSCP) fingerprints (2), which were distinct from those of other oomycete pathogens known to attack begonia (1). These isolates produced proliferous, ovoid to globose, terminal, and papillate sporangia which were 30.6 to 45.4 µm (av. 38.7 µm) in length and 20.5 to 35.4 µm (av. 28.2 µm) in width. Oogonia were produced in single culture grown in clarified V8 juice agar. These smooth-walled oogonia were mostly aplerotic and 28.9 to 36.8 µm (av. 33.1 µm) in diameter. Each contained a single oospore with a diameter of 23.7 to 34.4 µm (av. 26.9 µm). Single to multiple antheridia were attached lengthwise to each oogonium. These morphological characteristics match the description of Phytopythium helicoides (= Pythium helicoides) (3). The identity of these isolates was confirmed by sequencing the rDNA internal transcribed spacer (ITS) 1 and 2 regions. ITS sequence of the representative isolate 55C7 (GenBank Accession No. KC907734) had 97 to 99% homology with P. helicoides sequences in GenBank. Two isolates, 55C7 and 56A7, were tested for pathogenicity to begonia in the summer of 2012. Twelve plants per isolate were inoculated by injecting ground P. helicoides-colonized rice grains into the root soil using a long-neck funnel. Sterile rice grains were used on control plants. Aboveground symptoms including foliar blight, stem rot, and collapsing crown were observed 7 days after inoculation and the disease progressed for additional 6 weeks. At 7 weeks, all inoculated plants showed different symptom levels. Four and 10 plants inoculated with 55C7 and 56A7, respectively, were already dead. Begonia roots showed severe symptoms including blackening, stunted growth, and rotting. Seven of 12 control plants also had notable symptoms due to cross contamination. Isolates recovered from all symptomatic plants had identical SSCP fingerprints to those of isolates 55C7 and 56A7. To our knowledge, this is the first report of P. helicoides attacking begonia plants. The avenue of this pathogen entering the 2011 field trial remains unknown. The field trial in 2011 and pathogenicity test in 2012 indicate that this pathogen is potentially destructive to begonia. Additional research is warranted to identify the origin and dissemination of this pathogen to mitigate the risk to begonia production. References: (1) C. X. Hong et al. Plant Dis. 92: 1201, 2008. (2) P. Kong et al. FEMS Microbiol. Lett. 240:229, 2003. (3) A. J. van der Plaats-Niterink. Monograph of the Genus Pythium. Centraalbureau voor Schimmelcultures, Baarn, the Netherlands, 1981.

Host Specificity and Variations in Aggressiveness of North Carolina Isolates of Phytophthora cryptogea and P. drechsleri in Greenhouse Ornamental Plants.

Three isolates of Phytophthora cryptogea and three isolates of P. drechsleri were evaluated for host specificity and variations in aggressiveness on eight floriculture crops commonly grown in North Carolina. Plants were monitored for the development of foliar symptoms stemming from root rot caused by Phytophthora. No isolates of P. cryptogea or P. drechsleri had the same host range, though all P. cryptogea isolates caused foliar symptoms on gerbera daisy and annual stock, and all P. drechsleri isolates incited disease on osteospermum. No African marigold plants developed foliar symptoms of Phytophthora root rot. All P. cryptogea isolates caused foliar symptoms on at least three tested plant species. Isolates of P. drechsleri varied from highly specific and only causing disease on a single host species to relatively nonspecific and causing foliar symptoms on the majority of host plants. This is the first report of host specificity of ornamental isolates of P. drechsleri, and several of the tested plants are not reported hosts of P. drechsleri. Differences in isolate aggressiveness were found and depended on plant species; overall, isolates of P. drechsleri were more aggressive than P. cryptogea isolates. Isolations from nonsymptomatic inoculated plants suggest that these Phytophthora spp. could be moved between growers or from growers to consumers on nonsymptomatic infected ornamentals.

Diversity and Mefenoxam Sensitivity of Phytophthora spp. Associated with the Ornamental Horticulture Industry in the Southeastern United States.

Phytophthora isolates associated with ornamental plants or recovered from irrigation water in six states in the southeastern United States (Georgia, North Carolina, South Carolina, Tennessee, Texas, and Virginia) were identified and screened for sensitivity to mefenoxam. Isolates from forest and suburban streams in Georgia and Virginia were included for comparison. A new in vitro assay, utilizing 48-well tissue culture plates, was used to screen for mefenoxam sensitivity; this assay allowed high throughput of isolates and used less material than the traditional petri plate assay. In total, 1,483 Phytophthora isolates were evaluated, and 27 species were identified with Phytophthora nicotianae, P. hydropathica, and P. gonapodyides, the most abundant species associated with plants, irrigation water, and streams, respectively. Only 6% of isolates associated with plants and 9% from irrigation water were insensitive to mefenoxam at 100 µg a.i./ml. Approximately 78% of insensitive isolates associated with plants were P. nicotianae, and most of these (67%) came from herbaceous annual plants. Most of the insensitive isolates recovered from irrigation water were P. gonapodyides, P. hydropathica, P. megasperma, and P. pini, and 83% of the insensitive isolates from streams were P. gonapodyides. Overall, this study suggests that mefenoxam should continue to be a valuable tool in the management of Phytophthora diseases affecting ornamental plants in the southeastern United States.

Micro-duplications of 1q32.1 associated with neurodevelopmental delay.

Distal partial trisomies involving the region 1q32 have been associated with dysmorphic features and developmental delay [1-11]. To further define the critical region for developmental delay and to investigate the genotype-phenotype association of 1q trisomy syndrome, we report two patients with much smaller (3 Mb and 3.5 Mb in size) trisomic regions on 1q32.1. The two micro-duplications largely overlap and both patients exhibited cognitive and motor delays. Case 1 is a 5-year-old boy with global developmental delay, behavioral problems, pervasive developmental disorder not otherwise specified (PDD-NOS), staring spells, headaches, and paresthesias. Case 2 is a 14-year-old girl with seizures, cognitive and motor difficulties, and minor dysmorphic features. These two cases suggest that 1q32.1 region on distal arm of 1q and genes involved are critical to cognitive and motor development in a gene dosage sensitive manner and that other neurological features are variable within this syndrome.

Phylogenetic history of Phytophthora cryptogea and P. drechsleri isolates from floriculture crops in North Carolina greenhouses.

The evolutionary history of Phytophthora cryptogea and P. drechsleri isolates previously collected from floriculture crops in North Carolina commercial greenhouses was explored with coalescent- and parsimony-based analyses. Initially, 68 isolates representing 13 location-host groups were sequenced at multiple loci. Sequences of all isolates within a group were identical. A subset of isolates were selected, cloned to resolve heterozygous sites, and analyzed with SNAP Workbench. The internal transcribed spacer (ITS) region of the ribosomal DNA and cytochrome oxidase II gene genealogies were congruent and indicated that P. cryptogea and P. drechsleri are sister species diverged from a common ancestor with no evidence of gene flow. In contrast, genealogies inferred from ß-tubulin (ß-tub) and translation elongation factor 1α (EF-1α) genes were in conflict with these loci. Coalescent analysis based on a nonrecombining partition in ß-tub and EF-1α showed an initial (older) split between P. cryptogea and P. drechsleri, with a later (recent) event separating the remaining P. cryptogea haplotypes from P. drechsleri. A parsimony-based minimal ancestral recombination graph inferred recombination between P. cryptogea and P. drechsleri isolates in the ITS region and ß-tub, suggesting genetic exchange between species. Also, putative recombination between A1 and A2 mating types of P. cryptogea suggests that sexual reproduction has occurred in the history of these P. cryptogea isolates.

Rufinamide for the treatment of epileptic spasms.

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of rufinamide for treatment of epileptic spasms. METHODS: We retrospectively reviewed patients treated with rufinamide for epileptic spasms from January 2009 to March 2010. Age, presence of hypsarrhythmia, change in seizure frequency following rufinamide initiation, and side effects were assessed. Patients who had a ≥ 50% reduction in spasm frequency were considered responders. RESULTS: Of all 107 children treated with rufinamide during the study period, 38 (36%) had epileptic spasms. Median patient age was 7 years (range: 17 months to 23). One patient had hypsarrhythmia at the time of treatment with rufinamide, and 9 other patients had a history of hypsarrhythmia. Median starting dose of rufinamide was 9 mg/kg/day (range: 2-18) and median final treatment dose was 39 mg/kg/day (range: 8-92). All patients were receiving concurrent antiepileptic drug therapy, with the median number of antiepileptic drugs being 3 (range: 2-6). Median duration of follow-up since starting rufinamide was 171 days (range: 10-408). Responder rate was 53%. Median reduction in spasm frequency was 50% (interquartile range=-56 to 85%, P<0.05). Two patients (5%) achieved a >99% reduction in spasms. Rufinamide was discontinued in 7 of 38 patients (18%) because of lack of efficacy, worsening seizures, or other side effects. Minor side effects were reported in 14 of 38 patients (37%). CONCLUSIONS: Rufinamide appears to be a well-tolerated and efficacious adjunctive therapeutic option for children with epileptic spasms. A prospective study is warranted to validate our observations.

Characterization of Phytophthora spp. on Floriculture Crops in North Carolina.

Isolates of Phytophthora in floriculture crops were collected from North Carolina commercial greenhouse facilities in 2007 and 2008, identified, and characterized for mating type and mefenoxam sensitivity. In all, 163 isolates from 13 host species at 11 locations were identified primarily as Phytophthora nicotianae (59%), P. drechsleri (23%), P. cryptogea (9%), and P. tropicalis (4%). Multiple Phytophthora spp. were found at five locations. DNA sequencing was more reliable for differentiating P. cryptogea and P. drechsleri. Only the A1 mating type of P. drechsleri was collected; however, both mating types of P. nicotianae, P. cryptogea, and P. tropicalis were found. Overall, 66% of Phytophthora isolates were resistant or intermediate in resistance to mefenoxam at 1 µg a.i./ml. Three groups of P. drechsleri isolates had effective concentration of mefenoxam providing 50% growth inhibition (EC50) estimates over 700 µg a.i./ml. EC50 estimates for P. nicotianae ranged from 246 to 435 µg a.i./ml. Isolates of P. nicotianae exhibited phenotypic heterogeneity at several locations, suggesting multiple separate introductions to the facilities. In contrast, P. nicotianae and P. drechsleri isolates from two locations were phenotypically identical to a previous survey, suggesting that the facilities have Phytophthora spp. established onsite.

Frequent musculoskeletal symptoms and reduced health-related quality of life among industrial workers.

The high percentage of musculoskeletal symptoms (MSS) found in studies of general populations and various occupational groups underlines the need to distinguish between severely and mildly affected individuals. To investigate associations between MSS and quality of life, we examined the frequency of MSS on a five-point scale, health-related quality of life (SF-36) and sickness absence among 5654 workers in the aluminium industry. High frequencies of MSS from all body parts were related to lower scores on the SF-36 and increased sickness absence. This relationship was strongest for MSS from the lower back. Workers who reported low back MSS 'very often' had a mean role--physical score equivalent to that of the 15th percentile of the general population. These results show that workers who reported MSS often or very often were severely affected, and this scale can therefore be used to distinguish individuals at high risk for reduced health-related quality of life and sickness absence.

Pulmonary resection for multi-drug resistant tuberculosis.

OBJECTIVES: Mycobacterium tuberculosis continues to be a major cause of morbidity and mortality throughout the world. Complacency by the medical profession and by patients has caused a new strain of Mycobacterium tuberculosis to emerge that is highly resistant to current antibiotics. The possibility of a new worldwide epidemic of drug-resistant Mycobacterium tuberculosis is of concern. Optimal therapy for patients infected with multi-drug resistant tuberculosis often requires surgical intervention to eradicate the infection. We report on our experience with pulmonary resection for multi-drug resistant tuberculosis. METHODS: During a 17-year period, 172 patients underwent 180 pulmonary resections. All patients had multi-drug resistant tuberculosis and had a minimum of 3 months of medical therapy before surgery. Muscle flaps were frequently used to avoid residual space and bronchial stump problems. RESULTS: During the study period, 98 lobectomies and 82 pneumonectomies were performed. Eight patients underwent multiple procedures. Operative mortality was 3.3% (6/180). Three patients died of respiratory failure, 2 patients died of a cerebrovascular accident, and 1 patient had a myocardial infarction. Late mortality was 6.8% (11/166). Significant morbidity was 12% (20/166). One half (91) of the patients had positive sputum at the time of surgery. After the operation, the sputum remained positive in only 4 (2%) patients. Mean length of follow-up was 7.6 years (range 4-204 months). CONCLUSIONS: Surgery remains an important adjunct to medical therapy for the treatment of multi-drug resistant Mycobacterium tuberculosis. In the setting of localized disease, persistent sputum positivity, or patient intolerance of medical therapy, pulmonary resection should be undertaken. Pulmonary resection for multi-drug resistant tuberculosis can be performed with acceptable operative morbidity and mortality.

Concordance of the toxicity of pharmaceuticals in humans and in animals.

This report summarizes the results of a multinational pharmaceutical company survey and the outcome of an International Life Sciences Institute (ILSI) Workshop (April 1999), which served to better understand concordance of the toxicity of pharmaceuticals observed in humans with that observed in experimental animals. The Workshop included representatives from academia, the multinational pharmaceutical industry, and international regulatory scientists. The main aim of this project was to examine the strengths and weaknesses of animal studies to predict human toxicity (HT). The database was developed from a survey which covered only those compounds where HTs were identified during clinical development of new pharmaceuticals, determining whether animal toxicity studies identified concordant target organ toxicities in humans. Data collected included codified compounds, therapeutic category, the HT organ system affected, and the species and duration of studies in which the corresponding HT was either first identified or not observed. This survey includes input from 12 pharmaceutical companies with data compiled from 150 compounds with 221 HT events reported. Multiple HTs were reported in 47 cases. The results showed the true positive HT concordance rate of 71% for rodent and nonrodent species, with nonrodents alone being predictive for 63% of HTs and rodents alone for 43%. The highest incidence of overall concordance was seen in hematological, gastrointestinal, and cardiovascular HTs, and the least was seen in cutaneous HT. Where animal models, in one or more species, identified concordant HT, 94% were first observed in studies of 1 month or less in duration. These survey results support the value of in vivo toxicology studies to predict for many significant HTs associated with pharmaceuticals and have helped to identify HT categories that may benefit from improved methods.

Prevalence of musculoskeletal symptoms among aluminium workers.

The aim of this study was to determine the prevalence of musculoskeletal symptoms (MSS) in workers in the aluminium industry, and to test the relationship with work by using the duration of employment as a measure of exposure. A total of 5654 workers (92%) answered a questionnaire. Operators, who were more exposed to physically demanding work, showed a greater incidence of MSS than did office workers. Among operators, the duration of employment was significantly correlated with MSS in nine out of ten areas of the body, when adjusted by multiple regression analyses for age, gender, height, weight, smoking and physical activity. Among office workers this relationship was weaker and was significant only for neck and lower back areas. The higher prevalence of MSS among operators and the association between their duration of employment and MSS suggests that a higher risk of MSS is related to the working environment.

Use of transgenic animals for carcinogenicity testing: considerations and implications for risk assessment.

Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA-/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.

Prenatal cocaine and neuromotor outcome at four months: effect of duration of exposure.

The effect of prenatal cocaine exposure on the motor development of full-term infants was examined in a prospective study, controlling for maternal characteristics and exposure to other substances. Intrauterine cocaine exposure was determined at birth by maternal self-report and was verified by hair analysis. At 4 months, 120 cocaine-exposed (COC) and 186 non-cocaine-exposed (NON-COC) infants were assessed by blinded examiners using a standard evaluation of neuromotor function, the Movement Assessment of Infants (MAI). Relative to NON-COC infants, COC infants had significantly higher full-scale MAI total risk scores after adjusting for covariates (p = .05). Infants exposed through the third trimester of pregnancy (n = 48) had higher MAI scores for both total risk (p = .02) and Volitional Movement (p = .01), and when compared with infants exposed only within the first two trimesters (n = 72), they had significantly more deficits in Volitional Movement (p = .03). Although MAI scores for the majority of exposed infants were within the normal range, infants exposed through the third trimester were at significantly increased risk for motor dysfunction (relative risk = 1.6; 95% confidence interval = 1.1, 2.8). Intrauterine cocaine exposure had an adverse effect on infant motor development after the neonatal period; this association was related to the timing and duration of gestational exposure. Further study is needed to evaluate the long-term clinical implications of neuromotor abnormalities in prenatally exposed infants.

Pregnant adolescents in chemical dependency treatment. Description and outcomes.

This study examines the treatment, maternal and infant outcomes of pregnant adolescents (16-19 years) enrolled in an adult perinatal chemical dependency treatment program. Twenty-one adolescent subjects were compared to 323 adult women (mean age, 27.4 years) after enrollment into a randomized treatment trial consisting of intensive outpatient or short-term residential conditions. The results show a similar treatment retention rate. Adolescents differed from adult women on marital status, drugs of choice (alcohol, marijuana vs. opiates and cocaine) and method of administration, with no injection drug users in the adolescent cohort. Tobacco use was high (> 85%) in both groups. Obstetric, maternal, and infant outcomes to 1 year were comparable. Older adolescents who are chemically dependent and pregnant have treatment needs similar to adult women and can benefit from programs designed to treat older women. Recruitment difficulties for adolescents in need of treatment is discussed.

PIP: This study describes a sample of 21 pregnant women aged 16-19 years in treatment for substance abuse through the MOMS Project in Seattle, Washington, during 1991-94 who were followed for at least 90 days after the beginning of treatment with regard to a number of variables. The treatment, maternal, and infant outcomes of these pregnant adolescents enrolled in an adult perinatal chemical dependency treatment program are compared with like outcomes for 323 randomized adults of mean age 27.4 years in the program. The randomized treatment trial involved either intensive outpatient or short-term residential conditions. 27% of adolescents and 32% of adults remained in treatment for longer than 90 days, a statistically nonsignificant difference. The adolescents did, however, differ from adult women on marital status, preferred drugs, and the method of drug administration, with no IV drug users among the adolescents. A larger proportion of the adolescents drank alcohol compared to the adults. More than 85% of the women in both groups smoked cigarettes. Obstetric, maternal, and infant outcomes to 1 year were comparable. These findings demonstrate that older adolescents who are chemically dependent and pregnant have treatment needs similar to adult women and can benefit from programs designed to treat older women.

The role of infection in atherosclerosis and coronary artery disease: a new therapeutic target.

There is growing evidence that inflammatory processes may be involved in the development of atherosclerosis and its complications. Viral and bacterial pathogens have been implicated as possible causative factors in the pathogenesis of coronary artery disease (CAD) and restenosis after angioplasty. Antibiotic trials are now in progress to examine whether treatment of infection can prevent the complications of CAD. Atherosclerosis, the primary pathologic process in coronary artery disease (CAD), carotid artery disease, abdominal aortic aneurysm, and peripheral vascular disease, is no longer considered to be an obscure, slowly progressive, degenerative disease. Indeed, recent molecular studies on the atherosclerotic plaque have shown that the initiation, progression, and acute sequelae of atherosclerosis can be explained in part by a low-grade inflammatory process. Studies show that mediators of inflammation can be found at all stages of the life cycle of the atherosclerotic plaque. These include activated macrophages and lymphocytes, cytokines, growth factors, matrix degenerating proteinases, and tissue factor. It is hypothesized that risk factors such as hypertension, smoking, or elevated levels of low-density lipoprotein (LDL) cholesterol result in injury to the endothelial cell of the artery, and this injury initiates the inflammatory process. However, many patients with vascular disease do not have these established risk factors, and this observation has galvanized efforts to find new risk factors. Because inflammation is now considered to be an operative paradigm for atherosclerosis, it is not a major leap to the hypothesis that infectious agents, such as viral or bacterial, may play a role. Certainly this is not a new concept, and with the recent discovery that peptic ulcer disease, heretofore considered a disease of excess acid and reduced mucosal resistance, is caused by the ubiquitous bacterium Helicobacter pylori, interest in finding an infectious etiology for atherosclerosis has increased. Accordingly, the purpose of this discussion is to review in a historical manner the evidence that infectious agents-including herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), Enterovirus (adenovirus, Coxsackie virus), Chlamydia pneumoniae, and H. pylori-may play a role in atherosclerosis and its manifestations, especially as they relate to CAD.