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Objective: Thyroid cancer has a disproportionately negative effect on quality of life (QOL) compared to malignancies with a worse prognosis. QOL of patients with indeterminate thyroid nodules has not been previously evaluated. We aimed to assess the impact of molecular test results on QOL of patients with indeterminate thyroid nodules. Methods: A short version of the Thyroid-Related Patient-Reported Outcome (ThyPro-39) assessed QOL of patients who underwent thyroid fine needle aspiration (FNA) biopsy throughout UCLA Health from May 2016 to June 2017. All patients with indeterminate biopsy results underwent molecular testing with either Afirma Gene Expression Classifier (GEC) or ThyroSeq v2 at the time of the initial biopsy. QOL associated with symptoms of goiter, anxiety, depression, and impaired daily life were analyzed. Results: Of 825 consented patients, 366 completed the assessment (44.4% response rate). FNA results included 76% benign, 7% malignant, and 17% indeterminate. There were no differences in QOL between patients with a benign FNA and patients with an indeterminate result with benign molecular testing. In patients with an indeterminate FNA, symptoms of goiter (20.5 vs. 10.4, P = 0.033) and depression (33.3 vs. 21.0, P = 0.026) were worse for patients with suspicious versus benign molecular test results; however, no significant differences were observed in anxiety or impaired daily life. Conclusions: A benign molecular test result may provide reassurance for patients with indeterminate thyroid nodules that the risk of malignancy is low. Long-term follow-up is necessary to determine if benign molecular test results maintain improved QOL.

Introduction Mild parkinsonian signs (MPS) are associated with morbidity. Identification of MPS progression markers may be vital for preventive management, yet has not been pursued. This study aimed to ascertain clinical/neuroimaging features predictive of MPS progression. Methods 205 participants in the Health ABC Study were included. MPS was defined using published guidelines. MPS progression was evaluated by determining UPDRS-III change between baseline and follow-up ≥2 years later. Standard brain MRI and DTI were obtained at baseline. Correlation coefficients between demographics, vascular risk factors, imaging markers, and UPDRS-III change were adjusted for follow-up time. Linear regression was used to adjust for possible confounders in the relationship between imaging markers and MPS progression. Results 30% of participants had baseline MPS. Demographics and risk factors did not differ significantly between participants with MPS (MPS+) and without MPS (MPS-). Mean follow-up time was 3.8±0.8 years. Older age, male gender, diabetes were associated with faster rate of UPDRS-III change in MPS- but not MPS+ participants. Among MPS- participants, the only imaging marker associated with faster UPDRS-III progression was higher gray matter mean diffusivity (MD), widespread in various cortico-subcortical bihemispheric regions, independent of age, gender, diabetes. No imaging features were associated with UPDRS-III change among MPS+ participants. Conclusions Lower gray matter integrity predicted MPS progression in those who did not have baseline MPS. Microstructural imaging may capture early changes related to MPS development, prior to macrostructural change. Any future management promoting gray matter preservation may inhibit MPS development.

Lithium (Li) carbonate has been established as a mood stabilizer and an efficacious treatment for bipolar disorder since its discovery by Dr. John Cade in 1948. Li interacts significantly with organ systems and endocrine pathways. One of the most challenging side effects of Li to manage is its effect on the parathyroid glands. Dysregulation of parathyroid signaling due to Li results in hypercalcemia due to increased vitamin D3 generation, increased calcium absorption from the gut, and bone resorption, occasionally resulting in concomitant hypercalciuria. However, hypercalciuria is not a definitive feature for hyperparathyroidism, and normal calcium excretion might be seen in these patients. Hypercalcemia may also result from volume contraction and decreased renal clearance, which are commonly seen in these patients. Anatomically the parathyroid abnormalities can present as single or multiglandular disease. We report 3 cases where the patients developed multiple side effects of Li therapy as well as hypercalcemia due to hyperparathyroidism. The literature is reviewed with regard to medical and surgical management of Li-associated hyperparathyroidism in the context of these 3 presented cases.

Entomopathogenic fungi show great promise as pesticides in terms of their relatively high target specificity, low non-target toxicity, and low residual effects in agricultural fields and the environment. However, they also frequently have characteristics that limit their use, especially concerning tolerances to temperature, ultraviolet radiation, or other abiotic factors. The devastating ectoparasite of honey bees, Varroa destructor, is susceptible to entomopathogenic fungi, but the relatively warm temperatures inside honey bee hives have prevented these fungi from becoming effective control measures. Using a combination of traditional selection and directed evolution techniques developed for this system, new strains of Metarhizium brunneum were created that survived, germinated, and grew better at bee hive temperatures (35 °C). Field tests with full-sized honey bee colonies confirmed that the new strain JH1078 is more virulent against Varroa mites and controls the pest comparable to current treatments. These results indicate that entomopathogenic fungi are evolutionarily labile and capable of playing a larger role in modern pest management practices.

Purpose Descriptions of large series of accessory atrioventricular pathway (AP) ablations in adults and adolescents have been limited to referral centers and published over 20 years ago. We aimed to characterize contemporary accessory AP distribution and features in a large community-based population that influence ablation outcomes. Methods Retrospective analysis of 289 patients (age 14–81) who underwent AP ablation from 2015–2019 was performed. Pathways were categorized into anteroseptal (AS), left freewall (LFW), posteroseptal (PS), and right freewall (RFW) locations. We analyzed patient and pathway features to identify factors associated with prolonged procedure time parameters. Results Initial ablation success rate was 94.7% with long-term success rate of 93.4% and median follow-up of 931 days. APs were in LFW (61.6%), PS (24.6%), RFW (9.6%), and AS (4.3%) locations. Procedure outcome was dependent on pathway location. Acute success was highest for LFW pathways (97.1%) with lowest case times (144 ± 68 minutes) and fluoroscopy times (15 ± 19 minutes). Longest procedure time parameters were seen with AS, left anterolateral, epicardial-coronary sinus, and right anterolateral pathway ablations. A novel ECG algorithm was developed to predicts AP locations and further guide procedure planning. Conclusion In this community-based population, majority of APs are located in the left freewall and posteroseptal region, with only retrograde conduction, and can be ablated using traditional approaches with short time parameters and high success. Using a novel ECG algorithm for pathway localization, we can predict cases with longer procedure times, higher fluoroscopy exposure, and lower acute and long-term success for manifest pathways.

Sex chromosome evolution results in the disparity in gene content between heterogametic sex chromosomes and creates the need for dosage compensation to counteract the effects of gene dose imbalance of sex chromosomes in males and females. It is not known at which stage of sex chromosome evolution dosage compensation would evolve. We used global gene expression profiling in male and female papayas to assess gene expression patterns of sex-linked genes on the papaya sex chromosomes. By analyzing expression ratios of sex-linked genes to autosomal genes and sex-linked genes in males relative to females, our results showed that dosage compensation was regulated on a gene-by-gene level rather than whole sex-linked region in papaya. Seven genes on the papaya X chromosome exhibited dosage compensation. We further compared gene expression ratios in the two evolutionary strata. Y alleles in the older evolutionary stratum showed reduced expression compared to X alleles, while Y alleles in the younger evolutionary stratum showed elevated expression compared to X alleles. Reduced expression of Y alleles in the older evolutionary stratum might be caused by accumulation of deleterious mutations in regulatory regions or transposable element-mediated methylation spreading. Most X-hemizygous genes exhibited either no or very low expression, suggesting that gene silencing might play a role in maintaining transcriptional balance between females and males.

Assess the relationship between inhaled corticosteroid use (ICS) and weight (BMI) in pediatric patients with moderate-severe asthma. Assess if the number of emergency department (ED) visits correlates with overall BMI trajectory. Assess the trend of prescribing biologic therapy in pediatric patients with moderate-severe asthma and determine its relationship with weight (BMI).A retrospective chart review was performed on 93 pediatric patients with moderate-severe asthma to determine the relationship between ICS use and weight (BMI), biologic therapy and BMI, and number of ED visits and BMI trajectory. A mixed effects model was employed with the correlation between repeated measures accounted for through the random effects.There is a statistically significant increase of 0.369 kg/mThe potency of ICS use in pediatric patients with moderate-severe asthma affects BMI trajectory; the higher the dose, the greater the projected BMI increase per year. Initiation of biologic therapy decreased BMI trajectory over time. Lastly, those with frequent ED visits had a higher BMI trend. Future prospective studies are warranted that further evaluate the potential metabolic impacts of ICS and assess the effects of biologic therapy on BMI.

Background: Treatment options, together with guidelines, for pts with CLL have evolved and expanded with the introduction of novel agents. The informCLLTM registry is the largest US-based prospective, observational registry of pts who received treatment for CLL/SLL in the post-novel agent era. This prospective real-world registry is uniquely positioned to examine the impact of the dynamic treatment landscape, treatment practices, and outcomes in routine clinical setting. Here we present baseline characteristics, prognostic biomarker testing, and treatment patterns for the fully enrolled pt population. Methods: From Oct 2015 to June 2019, informCLL (PCYC-1134; NCT02582879) enrolled eligible pts with CLL/SLL who were ≥18 years (y), initiated FDA-approved treatment for CLL/SLL within ±45 days of enrollment and provided consent. Pts were classified into 5 groups based on treatment received at enrollment (index): ibrutinib (single agent or combination), chemoimmunotherapy (CIT), chemotherapy (CT), immunotherapy (IT), and other novel agents. Descriptive analyses are presented. Results: The registry fully enrolled with 1461 pts: 855 (59%) previously untreated and 606 (41%) relapsed/refractory (R/R) pts. Community-based practices enrolled 93% of pts. The median age was 71 y (33% ≥75 y), the majority were male (64%), and 88% had ECOG performance status of 0/1. For pts with staging performed at enrollment (n=852), 51% had Rai stage III/IV. Median (range) time from diagnosis to initial treatment on study was 18.6 months (mos, FISH testing was performed in 28% (n=415) of pts and was more frequent in previously untreated vs R/R pts (33% vs 21%). TP53 mutation testing was performed in 11% (n=162) of pts (previously untreated: 13%; R/R: 9%). IGHV mutational status testing was performed in 12% (n=171) of pts (previously untreated: 13%; R/R 10%). Of pts with prognostic biomarker testing, 24% (100/415) had del(17p), 27% (43/162) had TP53 mutation, and 71% (121/171) had unmutated IGHV. Prognostic biomarker testing by treatment group is shown in Figure 1. Table 1 shows the distribution of pts receiving different treatments on study. Across lines of therapy, the most common treatment was ibrutinib (46%); the majority (87%) started ibrutinib treatment at the recommended daily dose of 420 mg, and pts continuing ibrutinib therapy largely did not require dose modifications (75%). At 12 or 24 mos, 77% (307/401) and 68% (126/184) of pts continued on ibrutinib treatment, respectively. For pts who completed the most common CIT regimens (bendamustine + rituximab [BR] and fludarabine + cyclophosphamide + rituximab), 80% and 85%, respectively, received Conclusions: The informCLL registry provides an opportunity to prospectively assess CLL treatment patterns in the era of novel agents. The most common index treatment was ibrutinib and the majority of ibrutinib-treated pts remained on therapy at 2 y follow-up; CIT (primarily BR) was also used for one-third of patients. Prognostic biomarker testing rates were poor, especially for TP53 and IGHV mutational status. Data from informCLL also indicate a 'knowledge gap' in terms of prognostic marker testing and selection of therapies for pts with high-risk disease. Data from the now complete pt population and with continued follow up will allow for the ongoing evaluation of real-world treatment decisions and pt care that cannot be addressed by data from randomized clinical trials. Disclosures Mato: Janssen: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genentech: Consultancy, Research Funding; BeiGene: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; LOXO: Consultancy, Research Funding. Barrientos:Janssen: Honoraria; Oncternal Therapeutics: Research Funding; Sandoz: Consultancy; Gilead: Consultancy; Genentech: Consultancy; Bayer: Consultancy; AstraZeneca: Consultancy. Sharman:AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; BeiGene: Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding. Brander:BeiGene: Other, Research Funding; MEI Pharma: Other, Research Funding; DTRM: Other, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; ArQule: Consultancy, Other, Research Funding; Pfizer: Consultancy, Other; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; Ascentage: Other, Research Funding; Teva: Consultancy, Honoraria; Tolero: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Verastem: Consultancy, Honoraria, Other, Research Funding; NCCN: Other; Novartis: Consultancy, Other; NCCN: Other; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding. Kadish:Bluebird Bio: Current equity holder in publicly-traded company; Blueprint Medicines: Current equity holder in publicly-traded company; Teva Pharmaceutical: Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current equity holder in publicly-traded company; Editas Medicine: Current equity holder in publicly-traded company; Johnson & Johnson: Current equity holder in publicly-traded company; Sarepta Therapeutics: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company; Agios: Current equity holder in publicly-traded company; Celgene: Current equity holder in publicly-traded company, Speakers Bureau; Takeda: Speakers Bureau. Arango-Hisijara:Bristol-Myers Squibb: Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Upasani:AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment; Protagonist Therapeutics: Current Employment. Han:Johnson and Johnson: Current equity holder in publicly-traded company; Janssen: Current Employment, Other: Travel expenses. Huang:Janssen Scientific Affairs, LLC: Current Employment; Johnson & Johnson: Current equity holder in publicly-traded company. Iyengar:Express Scripts: Patents & Royalties; AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Ghosh:Karyopharm: Consultancy; Genmab: Consultancy, Speakers Bureau; SGN: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Celgene/Bristol-Myers Squibb: Speakers Bureau; AbbVie: Speakers Bureau; AstraZeneca: Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Roche/Genentech: Research Funding.

informCLL is the first United States-based registry of patients with chronic lymphocytic leukemia that initiated enrollment after approval of novel targeted agents. Prognostic/predictive testing rates and chronic lymphocytic leukemia treatment selection with availability of novel agents have not been previously investigated in clinical practice. Results from this interim analysis demonstrate that prognostic/predictive testing was infrequently used to guide treatment selection, potentially inhibiting beneficial outcomes for patients. Introduction: The therapeutic landscape for chronic lymphocytic leukemia (CLL) has significantly shifted with the approval of novel agents. Understanding current prognostic testing and treatment practices in this new era is critical. Beginning enrollment in 2015, informCLL is the first United States-based real-world, prospective, observational registry that initiated enrollment after approval of novel agents. Patients and Methods: Eligible patients were age ≥ 18 years, started CLL treatment within 30 days of enrollment, and provided consent. For this planned interim analysis, treatments were classified into 5 groups: ibrutinib, chemoimmunotherapy, chemotherapy, immunotherapy, and other novel agents. Results: Frequency of prognostic testing and treatment patterns are reported among 840 patients (459 previously untreated; 381 relapsed/refractory), enrolled largely (96%) from community practice settings. Testing for chromosomal abnormalities by fluorescence in situ hybridization, TP53 mutation, or IGHV mutation status occurred infrequently among all patients (31%, 11%, and 11%, respectively). Chemoimmunotherapy was the most common treatment in previously untreated patients (42%), whereas ibrutinib was the most common treatment among relapsed/ refractory patients (51%). Of patients who tested positive for del(17p) or TP53 mutation, 34% and 26% received chemoimmunotherapy, respectively. Among patients who did not have fluorescence in situ hybridization or TP53 mutation testing prior to enrollment, 33% and 32% received chemoimmunotherapy, respectively. Conclusion: Our findings indicate that prognostic testing rates were poor, and approximately one-third of high-risk patients (del[17p] and TP53) received chemoimmunotherapy, which is not aligned with current CLL treatment recommendations. This represents an opportunity to educate and alert health care professionals about the necessity of prognostic testing to guide optimal CLL treatment decisions.

Context Understanding clinical characteristics and treatment selection for elderly patients is essential in the era of novel agents. informCLL ( NCT02582879 , September 2015 initiation) is an ongoing, US-based, prospective, real-world observational registry of patients with CLL. Objective To characterize overall demographics of previously untreated elderly CLL patients and compare clinical factors and treatment choice of those aged 65-74 years (Group 1) versus ≥75 years (Group 2). Design/Patients An interim analysis (November 2018 data cut) of previously untreated patients from the informCLL registry who were aged ≥65 years and received single-agent ibrutinib, chemoimmunotherapy, or immunotherapy at enrollment. Association between age groups and treatment choice was assessed by multinomial logistic regression after adjusting for comprehensive demographic and clinical factors. Results Analysis included 449 elderly patients (Group 1: 238; Group 2: 211); median age was 74 years. Most patients were male (64.1%), white (92.4%), treated in community settings (94.9%), and Medicare/Medicaid-insured (88.4%). Median time from initial diagnosis to first treatment was 2.0 years. The majority had an Eastern Cooperative Oncology Group (ECOG) score ≤ 1 (87.1%) and Charlson Comorbidity Index (CCI) score ≤ 1 (62.0%). The most common comorbidities were hypertension (69.3%), other cardiovascular disorders (29.2%), non-CLL malignancies (26.3%), and connective tissue diseases (24.5%). Documented cytogenetic/molecular testing rates were low: TP53, 6.01%; IGHV, 5.35%; CLL FISH, 17.8%; any of the three, 18.7%. 202 (45.0%) patients received ibrutinib, 170 (37.9%) received chemoimmunotherapy, and 77 (17.1%) received immunotherapy. Group 2 (vs Group 1) had poorer performance status (ECOG scores ≥2, 12.9% vs 5.7%, p=0.01), more comorbidities (CCI scores ≥2, 45.5% vs 31.1%, p Conclusions Previously untreated real-world CLL patients aged ≥75 years (vs 65-74 years) had poorer performance status, more comorbidities, lower cytogenetic/molecular testing rates, and a higher likelihood of receiving ibrutinib versus chemoimmunotherapy as initial treatment.

Waves of highly infectious viruses sweeping through global honey bee populations have contributed to recent declines in honey bee health. Bees have been observed foraging on mushroom mycelium, suggesting that they may be deriving medicinal or nutritional value from fungi. Fungi are known to produce a wide array of chemicals with antimicrobial activity, including compounds active against bacteria, other fungi, or viruses. We tested extracts from the mycelium of multiple polypore fungal species known to have antiviral properties. Extracts from amadou (Fomes) and reishi (Ganoderma) fungi reduced the levels of honey bee deformed wing virus (DWV) and Lake Sinai virus (LSV) in a dose-dependent manner. In field trials, colonies fed Ganoderma resinaceum extract exhibited a 79-fold reduction in DWV and a 45,000-fold reduction in LSV compared to control colonies. These findings indicate honey bees may gain health benefits from fungi and their antimicrobial compounds.

Purpose: The link between childhood and adult obesity is becoming increasingly clear. Likewise, as a community of healthcare professionals, we have acknowledged the imminent threat of childhood obesity upon the future development of type 2 diabetes and cardiovascular diseases. However, we have not yet turned our attention towards adult-type oncogenesis. In the two counties that we serve, both with growing birth rates, childhood obesity is a significant burden, particularly affecting the young Hispanic population. Similarly, the Hispanic population disproportionately faces adult obesity and adult-type cancers. …

Great progress has been made in expanding our understanding of the natural history of movement disorders, leading to impressive advancements in their medical and surgical management. Movement disorders are a diverse group of diseases, varying widely in clinical characteristics and evolution. Some are monosymptomatic while others have associated motor and nonmotor features. Some are static while others follow a progressive course. This chapter will review common primary and secondary movement disorders: Parkinson disease and other forms of Parkinsonism, essential tremor and its differential diagnoses, dystonia and tic disorders. Herein, we will provide an overview of the clinical presentation and prognosis of the primary and secondary movement disorders most relevant to discussions of surgical candidacy.

At a time of resurgence in injection drug use and injection-attributable infections, needle stick injury (NSI) risk and its correlates among police remain understudied. In the context of occupational safety training, a convenience sample of 771 Baltimore city police officers responded to a self-administered survey. Domains included NSI experience, protective behaviors, and attitudes towards syringe exchange programs. Sixty officers (8%) reported lifetime NSI. Officers identifying as Latino or other race were almost three times more likely (aOR 2.58, 95% CI 1.12-5.96) to have experienced NSI compared to whites, after adjusting for potential confounders. Findings highlight disparate burdens of NSIs among officers of color, elevating risk of hepatitis, HIV, and trauma. Training, equipment, and other measures to improve occupational safety are critical to attracting and safeguarding police, especially minority officers.

Young women engaged in exotic dancing have a higher need for reproductive health services than women not in this profession, and many also use drugs or exchange sex for money or drugs. Few report receiving reproductive health services. We describe a public health, academic, and community partnership that provided reproductive health services on needle exchange mobile vans in the “red light district” in downtown Baltimore, Maryland. Women made 220 visits to the vans in the first 21 months of the program's operation, and 65% of these visits involved provision of contraception. Programmatic costs were feasible. Joint provision of needle exchange and reproductive health services targeting exotic dancers has the potential to reduce unintended pregnancies and link pregnant, substance-abusing women to reproductive care, and such programs should be implemented more widely.

A pediatric patient diagnosed initially with B-lymphoblastic leukemia (B-ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T-cell (CAR-T) therapy and hematopoietic stem cell transplant. A TCF3-ZNF384 fusion was identified at diagnosis, persisted through B-ALL relapse, and was also present in the AML relapse cell population. ZNF384-rearrangements define a molecular subtype of B-ALL characterized by a pro-B-cell immunophenotype; furthermore, ZNF384-rearrangements are prevalent in mixed-phenotype acute leukemias. Lineage switch following CAR-T therapy has been described in patients with KMT2A (mixed lineage leukemia) rearrangements, but not previously in any patient with ZNF384 fusion.

Background Transvenous lead extraction carries a risk of significant complications. Although intraoperative transesophageal echocardiography (TEE) is widely used to monitor cardiac performance and structures, its utility during transvenous lead extraction has not been well described. Objective This study evaluates the utility of TEE during transvenous lead extraction. Methods The records of 108 consecutive patients who underwent transvenous lead extraction with TEE guidance were reviewed. Results Transvenous extraction of 202 leads was attempted; complete extraction was achieved for 174 leads (86%) and partial extraction for 13 leads with clinically acceptable outcomes in 187 leads (93%). Mean age of the patients was 63 ± 21 (14-99) years and 37% were female. The average number of leads per patient was 1.9 (1-6). Mean implant duration was 71 ± 57 (1-360) months. Indications for extraction were pocket infection (53 patients), bacteremia (33), atrial J-lead fracture or recall (13), lead malfunction (8), and venous thrombosis (1). TEE identified critical findings that prompted emergency surgical intervention or converted transvenous lead extraction to surgical explantation in 6 patients (two cases with cardiac laceration, 3 cases of cardiac tamponade, and one case with a large vegetation and a patent foramen ovale). TEE eliminated the need for the premature termination of the procedure in 11 patients by excluding significant structural cardiac damage. Overall, TEE provided clinically useful information during transvenous lead extraction in 17 cases (16%). Conclusions TEE during transvenous lead extraction provides valuable real-time information that improves efficacy and safety.

Objectives. We piloted a monitoring mechanism to document police encounters around programs targeting people who inject drugs (PWID), and assessed their demographic predictors at 2 Baltimore, Maryland, needle exchange program (NEP) sites. Methods. In a brief survey, 308 clients quantified, characterized, and sited recent police encounters. Multivariate linear regression determined encounter predictors, and we used geocoordinate maps to illustrate clusters. Results. Within the past 6 months, clients reported a median of 3 stops near NEP sites (interquartile range [IQR] = 0–7.5) and a median of 1 arrest in any location (IQR = 0–2). Three respondents reported police referral to the NEP. Being younger (P = .009), being male (P = .033), and making frequent NEP visits (P = .02) were associated with reported police stops. Among clients reporting arrest or citation for syringe possession, Whites were significantly less likely than non-Whites to report being en route to or from an NEP (P Conclusions. Systematic surveillance of structural determinants of health for PWID proved feasible when integrated into service activities. Improved monitoring is critical to informing interventions to align policing with public health, especially among groups subject to disproportionate levels of drug law enforcement.

An inherent limitation to the study of in vivo animal models of lymphedema is the potential inaccuracy or unreliability of existing methods for the quantification of edema volume as a surrogate functional measure of lymphatic transport capacity. Circumference-based techniques have been proposed and validated as a suitable alternative to volume displacement measurements in human clinical studies; accordingly, we have elaborated a new application of this approach that can be applied to small animal studies.Acute postsurgical lymphedema was created experimentally in the murine tail. Both normal and lymphedematous murine tails were examined. Tail volume was quantitated both by water displacement and by a digital photographic technique. In selected mice, after sacrificed on postsurgical day 7, a 6 cm segment was resected from the midportion of the tail and cauterized to create a closed space. Known incremental volumes of saline (20-100 microL) were injected for subsequent digital photographic volumetry.The coefficients of variation for volume assessment by water displacement and by digital imaging were 0.08+/-0.09 and 0.01+/-0.009, respectively. The two techniques were poorly correlated: while serial water displacement analysis yielded highly variable measurements within the same tail, concurrent digital imaging of the tail circumference was quite reproducible. Furthermore, after parenteral injection of known incremental volumes of saline, the correlation between the injectate volumes and the digitally measured increases in volume was high, both in the normal and the lymphedematous tail.In the murine tail, when compared to water displacement volumetry, digital photography yields highly reproducible data. We can conclude that the lack of correlation between the two methods, with the relatively flat slope of the linear regression relationship, reflects inherent inaccuracies of the water displacement method.

Myotonic dystrophy (DM) is an autosomal dominant multisystem disorder, caused by expansion of a CTG trinucleotide repeat in the 3′ untranslated region of the myotonic dystrophy protein kinase gene (DMPK) on chromosome 19q13. Cardiac involvement in DM includes conduction abnormalities and functional deficits. Three hypotheses of molecular mechanisms for DM pathophysiology are; first, partial loss of myotonic dystrophy protein kinase (DMPK); second, decreased transcription of a neighboring homeodomain-encoding gene, Six5 (or DMAHP), and third, transdominant effects of the RNA and regulation of splicing associated with expression of expanded CUG repeats. However, the precise pathogenetic mechanism remains unresolved. We previously reported that dosage of Dm15, the mouse homologue of DMPK, strongly associates with the cardiac conduction abnormalities. For further distinction of the molecular mechanisms underlying the cardiac phenotype of DM, in the present study, we characterized the cardiac conduction findings of mice with targeted disruption of Six5 gene. Six5 heterozygous mice (adult and young) and their age matched wild type littermates were studied using in vivo electrophysiologic techniques, echocardiography, heart rate variability and exercise tolerance testing. No PR prolongation was detected, however, prolonged QRS duration and delayed infraHisian conduction were significant in adult Six5 heterozygous mice. By echocardiography, left ventricular (LV) end-diastolic dimension was enlarged in adult Six5 heterozygous mice, although neither fractioning shortening nor LV wall thickness showed significant differences. Six5 loss may partly contribute to conduction abnormalities in myotonic dystrophy, particularly infraHisian conduction delay, one of the initial phenotypes of adult-onset cardiac conduction abnormalities in DM patients.

Dissipation of Functional Bundle Branch Block. Introduction: Linking-related anterograde functional bundle branch block during supraventricular tachycardia (SVT) is due to repetitive concealed retrograde conduction of impulses from the contralateral bundle branch and can be eliminated by a critically timed premature ventricular beat (PVB). We assessed the electrophysiologic characteristics of PVB-induced dissipation of functional bundle branch block during SVT. Methods and Results: During SVT with functional bundle branch block, PVB was delivered from the right ventricular apex, scanning the tachycardia cycle length (CL) with 10-msec decrements in the coupling interval in 14 patients (3 AV nodal reentrant tachycardia and 11 orthodromic AV reciprocating tachycardia). Dissipation was achieved in group 1: functional right bundle branch block (RBBB) in 4, functional left bundle branch block (LBBB) in 4, and both functional RBBB and LBBB in 1 with a dissipation zone occupying 4% to 13% (mean 8.5%) of the tachycardia CL. The outer limits were 22 ± 16 msec and 68 ± 14 msec < tachycardia CL; the inner limits were 56 ± 18 msec and 90 ± 24 msec < tachycardia CL for RBBB and LBBB, respectively (both P < 0.05). Dissipation could not be achieved in group 2 (4 RBBB and 1 LBBB) due to CL-dependent bundle branch block and/or local ventricular refractoriness. Conclusion: During SVT, functional bundle branch block due to “linking” often can be dissipated by timely PVB delivered from the right ventricular apex within a narrow zone of the tachycardia CL. Our findings suggest that the dissipation zone is affected by the pattern of functional bundle branch block relative to the site of PVB delivery.

Objective: To determine whether specially devised catheters could be used to place radiofrequency (RF) linear lesions quickly and efficiently for termination and/or prevention of atrial fibrillation (AF).

Myotonic dystrophy (DM) is an autosomal dominant disorder characterized by skeletal muscle wasting, myotonia, cardiac arrhythmia, hyperinsulinaemia, mental retardation and ocular cataracts1. The genetic defect in DM is a CTG repeat expansion located in the 3′ untranslated region of DMPK and 5′ of a homeodomain-encoding gene, SIX5 (formerly DMAHP; refs 2–5). There are three mechanisms by which CTG expansion can result in DM. First, repeat expansion may alter the processing or transport of the mutant DMPK mRNA and consequently reduce DMPK levels6. Second, CTG expansion may establish a region of heterochromatin 3′ of the repeat sequence and decrease SIX5 transcription7,8,9. Third, toxic effects of the repeat expansion may be intrinsic to the repeated elements at the level of DNA or RNA (refs 10,11). Previous studies have demonstrated that a dose-dependent loss of Dm15 (the mouse DMPK homologue) in mice produces a partial DM phenotype characterized by decreased development of skeletal muscle force and cardiac conduction disorders12,13,14,15. To test the role of Six5 loss in DM, we have analysed a strain of mice in which Six5 was deleted. Our results demonstrate that the rate and severity of cataract formation is inversely related to Six5 dosage and is temporally progressive. Six5+/− and Six5−/− mice show increased steady-state levels of the Na+/K+-ATPase α-1 subunit and decreased Dm15 mRNA levels. Thus, altered ion homeostasis within the lens may contribute to cataract formation. As ocular cataracts are a characteristic feature of DM, these results demonstrate that decreased SIX5 transcription is important in the aetiology of DM. Our data support the hypothesis that DM is a contiguous gene syndrome associated with the partial loss of both DMPK and SIX5.

To discuss the role of bilateral adrenalectomy in Cushing syndrome, as illustrated in a case of severe hypercortisolism that was unresponsive to combination agent medical therapy.We report the clinical, laboratory, imaging, and pathologic findings in a patient with ectopic Cushing syndrome attributable to an adrenocorticotropic hormone (ACTH)-secreting neuroblastoma. In addition, we provide a literature review regarding olfactory neuroblastoma and discuss current and emerging therapeutic options for Cushing syndrome.A 59-year-old man presented with nasal congestion and neck swelling and was noted to have hypokalemia, hypertension, and hyperglycemia. A nasal biopsy demonstrated a poorly differentiated carcinoma with neuroendocrine features. He was subsequently diagnosed as having ACTH-dependent Cushing syndrome, but despite high-dose combination medical therapy, his condition rapidly deteriorated. Urgent bilateral adrenalectomy provided rapid control of the hypercortisolism, and the patient was later able to undergo an uncomplicated total macroscopic resection of his locally metastatic primary tumor.This report describes the challenges in the diagnosis and management of ACTH-dependent Cushing syndrome and highlights the important role that bilateral adrenalectomy can still have in patients with severe hypercortisolism causing life-threatening complications.

Evaluation of the efficacy of molecular treatment strategies for lymphatic vascular insufficiency requires a suitable preclinical animal model. Ideally, the model should closely replicate the untreated human disease in its pathogenesis and pathological expression.We have undertaken a study of the time course of the development and resolution of acquired, experimental lymphedema and of its responses to vascular endothelial growth factor (VEGF)-C lymphangiogenesis in the mouse tail model.We provoked post-surgical lymphedema in the mouse tail model and assessed the effects of exogenously administered human recombinant VEGF-C. Quantitative assessment of immune traffic function was performed through sequential in vivo bioluminescent imaging.In untreated lymphedema, tail edema was sustained until day 21. Exogenous administration of human recombinant VEGF-C produced a significant decrease in volume. Untreated lymphedema in the mouse tail model was characterized by the presence of dilated cutaneous lymphatics, marked acute inflammatory changes, and hypercellularity; VEGF-C produced a substantial reversion to the normal pattern, with notable regression in the size and number of cutaneous lymphatic vessels that express lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1). In vivo imaging confirmed the presence of an impairment of immune traffic in lymphedema that was ameliorated after VEGF-C administration.The post-surgical murine tail model of lymphedema closely simulates attributes of human lymphedema and provides the requisite sensitivity to detect therapeutically induced functional and structural alterations. It can, therefore, be used as an investigative platform to assess mechanisms of disease and its responses to candidate therapies, such as therapeutic lymphangiogenesis.

Background Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. Methods and Findings We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. Conclusions We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency., Editors' Summary Background. Lymphedema is the term used to describe the swelling that can occur after surgery, especially after axillary lymph node dissection for breast cancer, when the lymph vessels that carry protein-rich interstitial fluid from the tissues to the heart are damaged. Lymphedema can be extremely unpleasant and is very hard to treat; treatments that are currently used include those aimed to help massage the flow of lymph back to the chest. Lymphedema seems to be more than just accumulation of lymph, however, as changes also occur in the tissue surrounding the damaged lymph vessels. Currently, very little is known at the most basic level about what exactly these changes are, although they appear to be similar to an inflammatory process. One way of studying such a disease process in humans is to make an animal model that mimics the human condition and study the changes that occur there. For lymphedema, such a model can be made in the mouse tail by cutting lymph vessels there. Why Was This Study Done? The authors wanted to look closely at what happens in the tissues surrounding damaged lymph vessels to try to understand better what these changes are. They also wanted to study the movement of the cells that are normally carried in the lymph. What Did the Researchers Do and Find? The mouse model that the authors developed closely simulates the characteristics of human acquired lymphedema. In the mouse tails that had had their lymph vessels damaged, the authors were able to show that the tails were swollen compared with those of normal animals and of animals that hadhad sham (pretend) surgery. In the animals with lymphedema, many small lymph vessels were seen, as the lymph was unable to flow away normally. The area affected by the lymphedema had the appearance often seen in inflamed tissue, and analysis of genes from the same area to see how active, or “expressed,” they were showed changes that are often seen in, for example, acute inflammation and wound healing. The authors also showed that when these animals were injected with immune cells marked with a light marker, they were less able to remove the cells from the circulation. What Do These Findings Mean? These results show that the response to lymph stagnation is complex, but looks similar to that seen in acute inflammation. These results and this model may be useful in suggesting, and at a later date perhaps testing, treatments for lymphedema. One difference, however, between this mouse model and the condition in humans is that whereas lymphedema in humans is a rather chronic condition, here the researchers were only able to look at the changes over a short period of time. In a related Perspective article, Peter Carmeliet and colleagues further discuss the clinical relevance of these findings ( http://dx.doi.org/10.1371/journal.pmed.0030264). Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030254. • The National Cancer Institute has information for patients and health professionals on lymphedema • Cancerbackup is a United Kingdom cancer information service with information on many aspects of cancer, including lymphedema • The Lymphatic Research Foundation Description has information on lymphatic system research, Rockson and colleagues characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging, histopathological examination, and transcriptional profiling.

The recent article by Schwartz et al. addresses the intersection of two important public health issues: opiate substitution therapy and fatal heroin overdose.1 In the United States, drug overdose is responsible for more than 36 000 deaths annually2 and is the leading cause of death among illicit drug users. Baltimore, Maryland, has one of the highest per capita heroin addiction rates in the nation, with an estimated prevalence of heroin use in 10% of the population.3 Schwartz et al. conducted a 15-year ecological analysis in Baltimore and found that increases in buprenorphine and methadone treatment with concurrent decreases in overdose deaths, controlling for heroin purity. Along with previous research,4 this study demonstrates the far-reaching benefits of opiate agonist treatment. In Baltimore, an estimated 34% of 68 000 drug users were in drug treatment in 2011, with heroin being the primary drug of abuse.5 The magnitude of out-of-treatment drug users in Baltimore and in the United States underscores the need for overdose prevention efforts targeting this population. Furthermore, out-of-treatment, long-term injection drug users (IDUs) are at greatest risk for overdose.6,7 As Schwartz et al. noted, periods of abstinence resulting from recent incarceration or drug treatment are chief overdose risk factors, given associated decreases in tolerance.8,9 These facts speak to the importance of overdose prevention among active IDUs. Capital City Care, a medical marijuana dispensary, is shown in Washington, DC, on April 15, 2013, prior to the store's opening. Three years after Washington, DC, legalized medical marijuana, three stores are set to open, allowing patients with HIV/AIDS, ... As of 2012, there were an estimated 188 overdose prevention education and naloxone distribution programs (OPEND) in the United States.2 OPEND programs train peer drug users how to prevent overdoses and administer naloxone in the event of an overdose. Naloxone is a short-acting opiate antagonist that reverses the effects of respiratory depression commonly caused by opiate overdose.7 Since 2004, Baltimore’s OPEND program, Staying Alive, has reached 35 000 individuals including an estimated 10 000 IDUs, 1200 medical and drug treatment providers, and 8500 jail inmates. Staying Alive has distributed 4000 vials of naloxone, and 250 reversals have been reported. Between 2003 and 2009 (half of the study period examined in Schwartz et al.), Staying Alive distributed 1263 naloxone vials and 196 reversals were reported. We commend Schwartz et al. for their study, which highlighted important public health programs that appear to reduce overdose mortality. We believe that both OPEND and increased availability of opiate substitution therapy have contributed to decreases in overdose mortality in Baltimore. We think that both are necessary for a holistic approach to the issue of overdose.

Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia, Leydig cell hyperproliferation and increased follicle stimulating hormone (FSH) levels. DM1 results from a CTG expansion that causes transcriptional silencing of the flanking SIX5 allele. Loss of Six5 results in male sterility and a progressive decrease in testicular mass with age. We demonstrate a strict requirement of Six5 for both spermatogenic cell survival and spermiogenesis. Leydig cell hyperproliferation and increased intra-testicular testosterone levels are observed in the Six5-/- mice. Although increased FSH levels are observed in the Six5+/- and Six5-/- mice, serum testosterone levels and intra-testicular inhibin alpha and inhibin beta B levels are not altered in the Six5 mutant animals when compared with controls. Significantly, steady-state c-Kit levels are reduced in the Six5-/- testis. Thus, decreased c-Kit levels could contribute to the elevated spermatogenic cell apoptosis and Leydig cell hyperproliferation in the Six5-/- mice. The results support the hypothesis that the reduced SIX5 levels contribute to the male reproductive defects in DM1.

Myotonic dystrophy1 (DM1) is an autosomal dominant, multi-system disorder resulting from a CTG repeat expansion located in the 3' untranslated region of DMPK and immediately in the 5' of SIX5. Skeletal muscle, heart and smooth muscle are prominently affected in DM1. Endocrine abnormalities, gonadal atrophy, brain, skin, skeletal, immune and respiratory defects are also features of the disorder. Both DMPK and SIX5 levels are decreased in DM1 patients. Importantly, expression of mutant mRNAs encoding expanded CUG repeats has been shown to alter the activity of CUG repeat binding proteins in DM1. Mouse models have demonstrated that decreased levels of Dmpk, Six5 and the expression of expanded CUG repeats independently contribute to the development of DM1 pathology. However, an important gap in these studies is a lack of clear understanding of the expression pattern of Dmpk. We demonstrate that Dmpk mRNA is expressed in a range of adult mouse tissues that show pathology in DM1 including skeletal muscle, heart, smooth muscle, bone, testis, pituitary, brain, eye, skin, thymus and lung. Thus DMPK loss or CUG repeat expansion could contribute to DM1 pathology to these tissues. Dmpk mRNA is not detected in the ovary, pancreas or kidney. Significantly, Dmpk mRNA is expressed in the intestinal epithelium, cartilage and liver, which have not been reported to show consistent abnormalities in Dmpk(-/-) mice or in transgenic animals expressing CUG repeats. Taken together these data suggest that Dmpk loss or CUG repeat expression per se may not be sufficient to initiate pathology and are consistent with the hypothesis that coexpression of specific CUG repeat binding proteins with the mutant Dmpk mRNA or deregulation of genes such as Six5 that flank the CTG repeat tract may be necessary for DM1 to manifest.

s / Drug and Alcohol Dependence 140 (2014) e86–e168 e135 Contraception continuation among female exotic dancers seeking mobile reproductive health services concurrent with syringe exchange Caitlin E. Martin1, Mishka Terplan2, J. Han3, P. Chaulk4, C. Serio-Chapman3 1 Johns Hopkins Schools of Medicine and Public Health, Baltimore, MD, United States 2 Departments of Obstetrics, Gynecology, and Reproductive Sciences & Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, United States 3 Community Risk Reduction Services, Baltimore City Health Department, Baltimore, MD, United States 4 Bureau of HIV/STD Services, Baltimore City Health Department, Baltimore, MD, United States Aims: Female exotic dancers are an understudied population with a high prevalence of drug and alcohol use, risk factors for transactional sex and inconsistent condom use. In 2009, the Baltimore City Health Department expanded their mobile syringe exchange program to include reproductive health services in the “Red Light” district. The objective of this study was to describe depot medroxyprogesterone acetate (Depo-Provera) continuation patterns among female exotic dancers seeking these mobile health services. Methods: We performed a retrospective analysis of 75 clients who initiated Depo-Provera at a mobile health clinic attached to a syringe exchange from November 2009 to August 2012. Demographics, Depo-Provera uptake and continuation over 12 months were assessedby chart review. Characteristics between clientswho continued Depo-Provera at 3 months and those who did not were compared using chi-square and t-tests. Results: Seventy-two percent (N=52) of clients were African American, and 62% (N=42) were 24 years or younger. At 3 months, 36% (N=25) continued Depo-Provera. Clients who were Caucasian (p=0.03) and received other reproductive health services (p

The objective of this study was to characterize the autonomic effects of 2 interventions, head-up tilt and isoproterenol infusion, which alter autonomic balance by different mechanisms but produce the same RR intervals. We compared the effect of head-up tilt with the effect of isoproterenol on autonomic balance as measured by power spectral analysis of RR variability. Fifteen normal subjects had baseline measurements and then underwent head-up tilt. After return to baseline supine values, isoproterenol was infused at a rate of 1 microgram/min (low-dose isoproterenol), which was then increased to 2.1 +/- 0.5 microgram/min (high-dose isoproterenol). All subjects underwent a second tilt during high-dose isoproterenol, and 9 subjects completed this second tilt study. During the experiment, normal RR intervals were recorded and 5-minute segments were used to calculate power spectra. High-frequency (HF) power (0.15 to 0.40 Hz) was used as a measure of vagal activity. The effects of head-up tilt were compared with the effects of low-dose isoproterenol. Despite nearly identical mean RR intervals (784 ms with tilt vs 792 ms with low-dose isoproterenol, p = NS), there was significantly (p0.05) less HF power during head-up tilt in the drug-free state (172 ms2) than during low-dose isoproterenol in the supine position (307 ms2). A second head-up tilt was performed during the infusion of high-dose isoproterenol. During high-dose isoproterenol, tilt caused a decrease in RR intervals (from 573 to 491 ms; p0.01) and a decrease in HF power (from 68 to 28 ms2; p0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Young women engaged in exotic dancing have a higher need for reproductive health services than women not in this profession, and many also use drugs or exchange sex for money or drugs. Few report receiving reproductive health services. We describe a public health, academic, and community partnership that provided reproductive health services on needle exchange mobile vans in the “red light district” in downtown Baltimore, Maryland. Women made 220 visits to the vans in the first 21 months of the program’s operation, and 65% of these visits involved provision of contraception. Programmatic costs were feasible. Joint provision of needle exchange and reproductive health services targeting exotic dancers has the potential to reduce unintended pregnancies and link pregnant, substance-abusing women to reproductive care, and such programs should be implemented more widely. (Am J Public Health. 2012;102:1833–1836. doi:10.2105/AJPH.2012.300842)

A cinevideodensitometric method for measuring the dimensions of small vessels by computer analysis of digitized cineangiograms was developed and validated in radiographic phantom models. With this method, which is based on full-width-at-half-maximum analysis of videodensitometric profile curves, the diameters of contrast-filled plexiglass cylinders ranging from 1.78 mm to 4.14 mm in diameter were measured to within 2% mean error. The theoretical basis for this method of cinevideodensitometric analysis is provided.

The accuracy and reproducibility of caliper and cinevideodensitometric measurements of coronary stenotic dimensions were compared in radiographic phantom models and in coronary arteriograms of 28 patients undergoing coronary angioplasty. Projected, single-plane coronary cine frames were analyzed by a computer-assisted videodensitometric method, which measures stenotic cross-sectional area without assumptions about lesion geometry. The accuracy (2.4%) and precision (+/- 1.9%) of cinevideodensitometry for measuring percent area stenosis in Plexiglas models of eccentric stenotic lesions was superior to the accuracy (24.7%) and precision (+/- 5.4%) of caliper measurements. Interobserver variability was significantly (p less than 0.05) better for cinevideodensitometric (r = 0.98; SEE = 6.4%) than for caliper measurements (r = 0.87; SEE = 13.1%). After angioplasty, percent diameter stenosis measured by calipers fell from 70 +/- 12% to 30 +/- 15%. Mean percent area reduction measured by cinevideodensitometry fell from 89.1 +/- 8% to 40.1 +/- 22% and stenotic area increased five-fold, from 0.59 +/- 0.5 to 3.47 +/- 1.6 mm2. Pre and post PTCA gradients did not correlate with lesion dimensions. Cinevideodensitometric measurements of absolute stenotic dimensions were more reproducible than relative measurements expressed as a percentage, due to the tapered caliber of normal arterial segments. Thus, cinevideodensitometric measurements were more accurate and reproducible than caliper measurements. The angiographic effects of coronary angioplasty are best measured by cinevideodensitometry, because residual lesions post PTCA are often eccentric, have indistinct margins, and are better characterized by changes in area than by changes in diameter.

Progression of coronary artery stenosis was measured using a quantitative, computer-assisted cinevideodensitometric method in 144 arterial segments in 44 subjects undergoing coronary arteriography on two separate occasions at least 6 months apart. Projected coronary arteriograms were digitized into 512 X 512 pixel mode and percent stenosis was calculated by comparing background-corrected videodensitometric values over stenotic and normal segments. Subjects underwent repeat coronary arteriography because of worsening symptoms of angina or heart failure; subjects with renal failure, coronary artery bypass grafts or cardiac transplant were excluded. Clinical variables determined at the time of the first arteriogram included age, sex, serum cholesterol, systolic blood pressure and presence or absence of cigarette smoking, diabetes mellitus and left ventricular hypertrophy. The mean interval between arteriograms was 29.3 months. Overall progression of coronary stenosis was observed in 40 of the 44 subjects; the mean progression at 24 months was 39% (90% confidence interval, 33 to 45%) and at 36 months was 48% (40 to 56%). The degree of overall progression was related to the length of time between arteriograms (F = 5.81, p less than 0.05) and to serum cholesterol level (F = 4.37, p less than 0.05). These data indicate that using an accurate, quantitative method, it is possible to measure progression of coronary artery atherosclerosis within 2 to 3 years of the initial arteriogram. Serum cholesterol appears to be an important determinant of disease progression.