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1.
Atmos Chem Phys ; 24(2): 1025-1039, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38348019

ABSTRACT

Future African aerosol emissions, and therefore air pollution levels and health outcomes, are uncertain and understudied. Understanding the future health impacts of pollutant emissions from this region is crucial. Here, this research gap is addressed by studying the range in the future health impacts of aerosol emissions from Africa in the Shared Socioeconomic Pathway (SSP) scenarios, using the UK Earth System Model version 1 (UKESM1), along with human health concentration-response functions. The effects of Africa following a high-pollution aerosol pathway are studied relative to a low-pollution control, with experiments varying aerosol emissions from industry and biomass burning. Using present-day demographics, annual deaths within Africa attributable to ambient particulate matter are estimated to be lower by 150 000 (5th-95th confidence interval of 67 000-234 000) under stronger African aerosol mitigation by 2090, while those attributable to O3 are lower by 15 000 (5th-95th confidence interval of 9000-21 000). The particulate matter health benefits are realised predominantly within Africa, with the O3-driven benefits being more widespread - though still concentrated in Africa - due to the longer atmospheric lifetime of O3. These results demonstrate the important health co-benefits from future emission mitigation in Africa.

2.
Adv Mar Biol ; 87(1): 31-60, 2020.
Article in English | MEDLINE | ID: mdl-33293015

ABSTRACT

Changes in the size structure of coral populations have major consequences for population dynamics and community function, yet many coral reef monitoring projects do not record this critical feature. Consequently, our understanding of current and future trajectories in coral size structure, and the demographic processes underlying these changes, is still emerging. Here, we provide a conceptual summary of the benefits to be gained from more comprehensive attention to the size of coral colonies in reef monitoring projects, and we support our argument through the use of case-history examples and a simplified ecological model. We neither seek to review the available empirical data, or to rigorously explore causes and implications of changes in coral size, we seek to reveal the advantages to modifying ongoing programs to embrace the information inherent in changing coral colony size. Within this framework, we evaluate and forecast the mechanics and implications of changes in the population structure of corals that are transitioning from high to low abundance, and from large to small colonies, sometimes without striking effects on planar coral cover. Using two coral reef locations that have been sampled for coral size, we use demographic data to underscore the limitations of coral cover in understanding the causes and consequences of long-term declining coral size, and abundance. A stage-structured matrix model is used to evaluate the demographic causes of declining coral colony size and abundance, particularly with respect to the risks of extinction. The model revealed differential effects of mortality, growth and fecundity on coral size distributions. It also suggested that colony rarity and declining colony size in association with partial tissue mortality and chronic declines in fecundity, can lead to a demographic bottleneck with the potential to prolong the existence of coral populations when they are characterized by mostly very small colonies. Such bottlenecks could have ecological importance if they can delay extinction and provide time for human intervention to alleviate the environmental degradation driving reductions in coral abundance.


Subject(s)
Anthozoa , Coral Reefs , Animals , Population Dynamics
3.
Adv Ther ; 37(7): 3292-3298, 2020 07.
Article in English | MEDLINE | ID: mdl-32451950

ABSTRACT

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is the classic progressive fibrosing interstitial lung disease (ILD), but some patients with ILDs other than IPF also develop a progressive fibrosing phenotype (PF-ILD). Information on use and cost of healthcare resources in patients with PF-ILD is limited. METHODS: We used USA-based medical insurance claims (2014-2016) to assess use and cost of healthcare resources in PF-ILD. Patients with at least two ILD claims and at least one pulmonologist visit were considered to have ILD. Pulmonologist visit frequency was used as a proxy to identify PF-ILD (at least four visits in 2016, or at least three more visits in 2016 vs. 2014). RESULTS: Of 2517 patients with non-IPF ILD, 15% (n = 373) had PF-ILD. Mean annual medical costs associated with ILD claims were $35,364 in patients with non-IPF PF-ILD versus $20,211 in the non-IPF ILD population. In 2016, patients with non-IPF PF-ILD made more hospital ILD claims than patients with non-IPF ILD (10.5 vs. 4.7). CONCLUSIONS: These findings suggest higher disease severity and overall healthcare use for patients with a non-IPF ILD manifesting a progressive fibrosing phenotype (non-IPF PF-ILD).


Interstitial lung disease (ILD) is a group of similar lung conditions with lung fibrosis, scarring, or inflammation of the lung tissue. Some patients with ILD also have worsening lung fibrosis, referred to as "progressive fibrosis" (PF-ILD). The most common type of PF-ILD is idiopathic pulmonary fibrosis (IPF), which has no known cause. Although much is known about IPF, there is limited information available on how often patients with ILDs other than IPF (non-IPF ILD) use healthcare, or the costs associated with the disease. This study used US medical insurance claims to gain further insights. The study examined data from over 2500 patients with non-IPF ILD, of which 15% had PF-ILD. Patients defined as having PF-ILD had higher yearly medical costs and used healthcare services more often than other patients with ILD. This study highlights the economic burden of non-IPF ILD with progressive fibrosis (non-IPF PF-ILD).


Subject(s)
Health Care Costs/statistics & numerical data , Idiopathic Pulmonary Fibrosis/economics , Idiopathic Pulmonary Fibrosis/physiopathology , Insurance Claim Review/statistics & numerical data , Lung Diseases, Interstitial/economics , Lung Diseases, Interstitial/physiopathology , Patient Acceptance of Health Care/statistics & numerical data , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Forecasting , Health Care Costs/trends , Humans , Idiopathic Pulmonary Fibrosis/epidemiology , Insurance Claim Review/trends , Lung Diseases, Interstitial/epidemiology , Male , Middle Aged , United States/epidemiology
4.
Nat Commun ; 11(1): 448, 2020 01 23.
Article in English | MEDLINE | ID: mdl-31974358

ABSTRACT

RNA polymerases (RNAPs) transcribe genes through a cycle of recruitment to promoter DNA, initiation, elongation, and termination. After termination, RNAP is thought to initiate the next round of transcription by detaching from DNA and rebinding a new promoter. Here we use single-molecule fluorescence microscopy to observe individual RNAP molecules after transcript release at a terminator. Following termination, RNAP almost always remains bound to DNA and sometimes exhibits one-dimensional sliding over thousands of basepairs. Unexpectedly, the DNA-bound RNAP often restarts transcription, usually in reverse direction, thus producing an antisense transcript. Furthermore, we report evidence of this secondary initiation in live cells, using genome-wide RNA sequencing. These findings reveal an alternative transcription cycle that allows RNAP to reinitiate without dissociating from DNA, which is likely to have important implications for gene regulation.


Subject(s)
DNA-Directed RNA Polymerases/genetics , Escherichia coli/enzymology , Transcription, Genetic , Adenosine Triphosphate/genetics , Cytidine Triphosphate/genetics , DNA/genetics , DNA/metabolism , DNA, Antisense/genetics , DNA-Directed RNA Polymerases/chemistry , DNA-Directed RNA Polymerases/metabolism , Escherichia coli/genetics , Microscopy, Fluorescence , Promoter Regions, Genetic , Single Molecule Imaging
5.
Curr Med Res Opin ; 35(11): 2015-2024, 2019 11.
Article in English | MEDLINE | ID: mdl-31328965

ABSTRACT

Objective: Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) develop a progressive fibrosing phenotype. We investigated the diagnosis and management of non-IPF ILDs using data from a survey of physicians and from US insurance claims. Methods: Pulmonologists, rheumatologists and internists in France, Germany, Italy, Japan, Spain, UK and US who had managed ≥10 patients with non-IPF ILDs in the past year, including those with progressive fibrosing ILDs, completed an online survey. Data on US insurance and prescription claims were obtained from a repository that aggregates data on claims routed from providers or pharmacies to payers. Results: In May-June 2017, 243 pulmonologists, 203 rheumatologists and 40 internists completed an online survey. Respondents estimated that 18-32% of patients diagnosed with non-IPF ILDs develop progressive fibrosis and that time from symptom onset to death in these patients was 61-80 months. Drug treatment was given to 50-75% of patients with non-IPF progressive fibrosing ILDs. Reasons for patients not being treated included that physicians considered patients to have mild or slowly progressing disease, or did not believe that available treatments are effective or well tolerated. Corticosteroids were the preferred first-line treatment for all types of non-IPF ILD. There was considerable heterogeneity in preferences for second- and third-line treatments. US insurance claims data from 3823 patients indicated that, in 2016, 50-75% of patients with ILDs received drug treatment (mostly corticosteroids) for their ILD. Conclusions: Physicians estimate that 18-32% of patients diagnosed with non-IPF ILDs develop a progressive fibrosing phenotype and that these patients experience significant delays in the diagnosis of ILD and the detection of progressive fibrosis. Between 25% and 50% of patients with progressive fibrosing ILDs do not receive drug therapy. There is an unmet need for effective and well tolerated treatments for progressive fibrosing ILDs.


Subject(s)
Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/therapy , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/therapy , Disease Progression , Humans , Phenotype
6.
Biol Bull ; 237(3): 283-291, 2019 12.
Article in English | MEDLINE | ID: mdl-31922904

ABSTRACT

Failed invasions can be a key component for understanding and controlling introduced populations because understanding mechanisms behind failures can improve effective controls. In 2000, the non-native sea anemone Sagartia elegans was first found in Salem, Massachusetts, and it recolonized each summer. No individuals of S. elegans have been found after 2010, despite intensive search efforts. A mismatch between the species' thermal tolerance and winter water temperature is the most likely mechanism for this failed invasion. In both laboratory- and field-based temperature growth studies, S. elegans began regressing at 11 °C, stopped asexually reproducing at 9 °C, and died by 4 °C. These temperatures are above the average winter sea surface temperature in the Gulf of Maine, therefore suggesting that S. elegans requires a warm-water refuge. Another potential contributor to the disappearance of S. elegans is low genetic diversity as a result of establishment of only females (likely clones) and no males.


Subject(s)
Sea Anemones , Animals , Female , Massachusetts , Seasons , Temperature
7.
PLoS One ; 12(11): e0188263, 2017.
Article in English | MEDLINE | ID: mdl-29161292

ABSTRACT

The ability to recognize individuals and track growth over time is crucial to population dynamics research as well as studies of animal behavior. Invertebrates are particularly difficult to track as they often molt, have regenerative capabilities, or lack hard parts to attach markers. We tested, in laboratory and field studies, a new way of marking sea anemones (order Actiniaria) by injection of three vital stains (i.e., neutral red, methylene blue, and fluorescein). Neutral red and methylene blue did not affect growth or survival, but fluorescein was lethal at high concentrations. Marked individuals could be identified up to seven months after injection with neutral red, six weeks with methylene blue, and three days with low concentrations of fluorescein. Neutral red could be used for long-term monitoring of growth and survival in the field, and in combination with methylene blue could be used to mark individuals in distinguishable patterns for short-term studies such as examining predator-prey interactions, movement of individuals, and recruitment survival.


Subject(s)
Fluorescein/pharmacology , Methylene Blue/pharmacology , Neutral Red/pharmacology , Sea Anemones/physiology , Staining and Labeling/methods , Animals , Behavior, Animal/physiology , Invertebrates/physiology , Population Dynamics
8.
Nucleic Acids Res ; 44(11): 5378-89, 2016 06 20.
Article in English | MEDLINE | ID: mdl-27025650

ABSTRACT

The NusA protein is a universally conserved bacterial transcription elongation factor that binds RNA polymerase (RNAP). When functioning independently, NusA enhances intrinsic termination. Paradoxically, NusA stimulates the function of the N and Q antiterminator proteins of bacteriophage λ. The mechanistic basis for NusA's functional plasticity is poorly understood. Here we uncover an effect of nascent RNA length on the ability of NusA to collaborate with Q. Ordinarily, Q engages RNAP during early elongation when it is paused at a specific site just downstream of the phage late-gene promoter. NusA facilitates this engagement process and both proteins remain associated with the transcription elongation complex (TEC) as it escapes the pause and transcribes the late genes. We show that the λ-related phage 82 Q protein (82Q) can also engage RNAP that is paused at a promoter-distal position and thus contains a nascent RNA longer than that associated with the natively positioned TEC. However, the effect of NusA in this context is antagonistic rather than stimulatory. Moreover, cleaving the long RNA associated with the promoter-distal TEC restores NusA's stimulatory effect. Our findings reveal a critical role for nascent RNA in modulating NusA's effect on 82Q-mediated antitermination, with implications for understanding NusA's functional plasticity.


Subject(s)
Bacterial Proteins/metabolism , RNA/genetics , RNA/metabolism , Transcription Termination, Genetic , Transcriptional Elongation Factors/metabolism , Bacterial Proteins/chemistry , Binding, Competitive , Models, Biological , Promoter Regions, Genetic , Protein Binding , Transcriptional Elongation Factors/chemistry , Viral Regulatory and Accessory Proteins/chemistry , Viral Regulatory and Accessory Proteins/metabolism
9.
Proc Natl Acad Sci U S A ; 113(3): 602-7, 2016 Jan 19.
Article in English | MEDLINE | ID: mdl-26733675

ABSTRACT

Production of a messenger RNA proceeds through sequential stages of transcription initiation and transcript elongation and termination. During each of these stages, RNA polymerase (RNAP) function is regulated by RNAP-associated protein factors. In bacteria, RNAP-associated σ factors are strictly required for promoter recognition and have historically been regarded as dedicated initiation factors. However, the primary σ factor in Escherichia coli, σ(70), can remain associated with RNAP during the transition from initiation to elongation, influencing events that occur after initiation. Quantitative studies on the extent of σ(70) retention have been limited to complexes halted during early elongation. Here, we used multiwavelength single-molecule fluorescence-colocalization microscopy to observe the σ(70)-RNAP complex during initiation from the λ PR' promoter and throughout the elongation of a long (>2,000-nt) transcript. Our results provide direct measurements of the fraction of actively transcribing complexes with bound σ(70) and the kinetics of σ(70) release from actively transcribing complexes. σ(70) release from mature elongation complexes was slow (0.0038 s(-1)); a substantial subpopulation of elongation complexes retained σ(70) throughout transcript elongation, and this fraction depended on the sequence of the initially transcribed region. We also show that elongation complexes containing σ(70) manifest enhanced recognition of a promoter-like pause element positioned hundreds of nucleotides downstream of the promoter. Together, the results provide a quantitative framework for understanding the postinitiation roles of σ(70) during transcription.


Subject(s)
DNA-Directed RNA Polymerases/metabolism , Escherichia coli/enzymology , Escherichia coli/genetics , Sigma Factor/metabolism , Transcription, Genetic , Base Sequence , Gene Expression Regulation, Bacterial , Kinetics , Lasers , Molecular Sequence Data , Nucleotides/metabolism , Photobleaching , RNA, Messenger/genetics , RNA, Messenger/metabolism , Templates, Genetic , Time Factors , Transcription Elongation, Genetic
10.
Elife ; 42015 Sep 15.
Article in English | MEDLINE | ID: mdl-26371553

ABSTRACT

The σ subunit of bacterial RNA polymerase (RNAP) confers on the enzyme the ability to initiate promoter-specific transcription. Although σ factors are generally classified as initiation factors, σ can also remain associated with, and modulate the behavior of, RNAP during elongation. Here we establish that the primary σ factor in Escherichia coli, σ(70), can function as an elongation factor in vivo by loading directly onto the transcription elongation complex (TEC) in trans. We demonstrate that σ(70) can bind in trans to TECs that emanate from either a σ(70)-dependent promoter or a promoter that is controlled by an alternative σ factor. We further demonstrate that binding of σ(70) to the TEC in trans can have a particularly large impact on the dynamics of transcription elongation during stationary phase. Our findings establish a mechanism whereby the primary σ factor can exert direct effects on the composition of the entire transcriptome, not just that portion that is produced under the control of σ(70)-dependent promoters.


Subject(s)
DNA-Directed RNA Polymerases/metabolism , Escherichia coli/physiology , Gene Expression , Sigma Factor/metabolism , Transcription Elongation, Genetic
12.
Pain ; 154(11): 2249-2261, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23748119

ABSTRACT

Neuropathic pain (NP) is often refractory to pharmacologic and noninterventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group, the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central poststroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: 1) epidural injections for herpes zoster; 2) steroid injections for radiculopathy; 3) SCS for FBSS; and 4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor radiofrequency lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials, long-term studies, and head-to-head comparisons among different interventional and noninterventional treatments.


Subject(s)
Neuralgia/therapy , Pain Management/standards , Complex Regional Pain Syndromes/physiopathology , Complex Regional Pain Syndromes/therapy , Failed Back Surgery Syndrome/complications , Failed Back Surgery Syndrome/physiopathology , Failed Back Surgery Syndrome/therapy , Humans , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/physiopathology , Peripheral Nervous System Diseases/therapy , Radiculopathy/complications , Radiculopathy/physiopathology , Radiculopathy/therapy , Randomized Controlled Trials as Topic , Trigeminal Neuralgia/physiopathology , Trigeminal Neuralgia/therapy
13.
Mayo Clin Proc ; 85(3 Suppl): S15-25, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20194144

ABSTRACT

The efficacy of drugs for neuropathic pain has been established in randomized controlled trials that have excluded patients with comorbid conditions and those taking complex medications. However, patients with neuropathic pain frequently present with complex histories, making direct application of this evidence problematic. Treatment of neuropathic pain needs to be individualized according to the cause of the pain, concomitant diseases, medications, and other individual factors. Tricyclic antidepressants (TCAs), gabapentinoids, selective noradrenergic reuptake inhibitors, and topical lidocaine are the first-line choices; if needed, combination therapy may be used. When a new drug is added, screening for potential drug interactions is recommended. The TCAs have anticholinergic adverse effects and may cause orthostatic hypotension. They should be avoided or used cautiously in patients with cardiac conduction disturbances or arrhythmias. Patients who lack cytochrome P450 2D6 isoenzyme activity are prone to adverse effects of TCAs and venlafaxine and have a weaker analgesic response to tramadol. A combination of several serotoninergic drugs may lead to serotonin syndrome. Risk of gastrointestinal tract bleeding is increased in patients taking selective serotonin reuptake inhibitors or venlafaxine, especially when combined with nonsteroidal anti-inflammatory drugs. Dose adjustment may be needed in patients with renal or hepatic impairment. Depending on the drug, the dose is reduced or the dosage interval lengthened. Slow titration and careful follow-up are needed. No drug is absolutely safe during pregnancy and lactation. Particular care must be exercised during the first trimester when drug dose should be as low as possible. Individual weighing of benefits and risks should guide therapeutic decisions.


Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Antidepressive Agents/therapeutic use , Neuralgia/drug therapy , Neuralgia/epidemiology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Analgesics, Non-Narcotic/adverse effects , Analgesics, Non-Narcotic/pharmacology , Antidepressive Agents/adverse effects , Antidepressive Agents/pharmacology , Antidepressive Agents, Tricyclic/adverse effects , Antidepressive Agents, Tricyclic/pharmacology , Antidepressive Agents, Tricyclic/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Comorbidity , Drug Interactions , Drug Therapy, Combination , Female , Gastrointestinal Hemorrhage/epidemiology , Gastrointestinal Hemorrhage/etiology , Humans , Kidney Diseases/drug therapy , Kidney Diseases/epidemiology , Liver Diseases/drug therapy , Liver Diseases/epidemiology , Male , Neuralgia/prevention & control , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/epidemiology , Randomized Controlled Trials as Topic , Risk Factors , Serotonin Syndrome/epidemiology , Serotonin Syndrome/etiology , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/pharmacology
14.
Mayo Clin Proc ; 85(3 Suppl): S3-14, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20194146

ABSTRACT

The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel alpha(2)-delta ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.


Subject(s)
Analgesics/therapeutic use , Antidepressive Agents/therapeutic use , Evidence-Based Medicine , Neuralgia/drug therapy , Acetamides/therapeutic use , Amines/therapeutic use , Analgesics, Opioid/therapeutic use , Anesthetics, Local/therapeutic use , Cyclohexanecarboxylic Acids/therapeutic use , Gabapentin , Humans , Lacosamide , Neuralgia/prevention & control , Practice Guidelines as Topic , Pregabalin , Randomized Controlled Trials as Topic , Selective Serotonin Reuptake Inhibitors/therapeutic use , gamma-Aminobutyric Acid/analogs & derivatives , gamma-Aminobutyric Acid/therapeutic use
15.
Am J Gastroenterol ; 104(2): 310-7, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19174783

ABSTRACT

OBJECTIVES: Dysplasia in a Barrett's esophagus (BE) is associated with an increased risk for developing esophageal adenocarcinoma. Ablation using the HALO system has shown promise for the treatment of BE with dysplasia. The objective of this study was to assess the safety and efficacy of a stepwise regimen of circumferential and focal ablation using the HALO system for the treatment of BE with dysplasia. METHODS: BE patients with low-grade dysplasia (LGD) or high-grade dysplasia (HGD) were enrolled. Primary circumferential ablation was followed every 3 months by further circumferential ablation or focal ablation until complete endoscopic eradication of BE was achieved. At 3- or 6-month intervals, depending on baseline grade, targeted and four quadrant random biopsies were obtained to assess the histological response to ablation. A complete response (CR) is defined as all biopsies negative for intestinal metaplasia (IM) (CR-IM) or dysplasia (CR-D) at last available follow-up. RESULTS: A total of 63 patients were treated (57 men; median age 71 years; median BE length 5 cm), with worst grade of dysplasia being LGD (n=39) and HGD (n=24). Follow-up is available for 62 patients (median 24 months). Overall, CR-IM is 79% and CR-D is 89%. For the LGD cohort, CR-IM is 87% and CR-D is 95%. For the HGD cohort, CR-IM is 67% and CR-D is 79%. CONCLUSIONS: Stepwise circumferential and focal ablation of BE containing dysplasia appears to be a safe and effective intervention, achieving a CR for dysplasia in 95% and 79% of LGD and HGD patients, respectively.


Subject(s)
Barrett Esophagus/pathology , Barrett Esophagus/surgery , Catheter Ablation/instrumentation , Endoscopy , Adult , Aged , Equipment Design , Female , Follow-Up Studies , Humans , Male , Metaplasia , Middle Aged , Mucous Membrane/pathology , Prospective Studies , Treatment Outcome
16.
Am J Gastroenterol ; 103(7): 1657-62, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18564119

ABSTRACT

BACKGROUND: The optimal interval of imaging studies for surveillance of incidental pancreatic cystic neoplasms is not known. OBJECTIVE: A retrospective analysis of longitudinal medical records of patients with pancreatic cystic neoplasms was performed to examine the natural history of incidentally detected cystic pancreatic neoplasms with respect to the development of significant growth and to identify predictors of such growth. RESULTS: After excluding patients with small (<10 mm) cysts (N = 144) and inadequate clinical follow-up of less than 6 months (N = 79) and those with a clinical diagnosis of pancreatic pseudocysts, serous cystadenoma, main duct intraductal papillary mucinous neoplasm (N = 29), and neuroendocrine tumor (N = 3), in total, 166 cysts in 150 patients were available for analysis. The working diagnoses on these cysts (based on clinical, radiological features, aspiration cytology, cyst fluid analysis, and surgical pathology data when available) were mucinous cystic neoplasm in 117 and branch-type intraductal papillary mucinous neoplasm in 49. The mean standard error (SE) initial size of these cysts was 2 (0.1) cm. Over a median period of follow-up of 32 (IQR [inter-quartile range] 19-48) months, 89% of all the cysts did not show significant growth during the follow-up. In a multivariate Cox proportional hazards model, the initial size of the cystic lesion was an independent predictor of significant growth during follow-up (relative risk 1.28, 95% confidence interval [CI] 1.08-1.61, P= 0.01); the only other significant variable was the presence of intracystic or mural nodule (relative risk 38.6, 95% CI 2.3-654, P= 0.01). CONCLUSION: Most incidentally detected cystic neoplasms of the pancreas did not have significant growth during follow-up. Such growth is unlikely to occur before 2 yr of the baseline evaluation, and we suggest that the optimal imaging interval during follow-up of these patients should be at 2 yr from the baseline evaluation, particularly in cystic lesions 3.0 cm or less in size and without intracystic or mural nodules.


Subject(s)
Pancreatic Cyst/diagnosis , Pancreatic Neoplasms/diagnosis , Aged , Disease Progression , Female , Humans , Incidental Findings , Male , Pancreatic Cyst/pathology , Pancreatic Neoplasms/pathology , Proportional Hazards Models , Retrospective Studies , Time Factors
17.
Gastrointest Endosc ; 68(2): 231-6, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18533150

ABSTRACT

BACKGROUND: Gastric antral vascular ectasia (GAVE) is characterized by mucosal and submucosal vascular ectasia causing recurrent GI hemorrhage. Treatment of GAVE with endoscopic thermal therapy (ETT) requires multiple sessions for destruction of vascular ectasia and control of bleeding. Endoscopic band ligation (EBL) has become the standard treatment of varices because it effectively obliterates the submucosal plexus of esophageal varices with an acceptably low rate of complications. Additionally, EBL has been used for control of bleeding from other GI vascular lesions. In patients with GAVE and recurrent GI hemorrhage, EBL may offer an alternative to ETT for treatment of large areas of diseased mucosa and submucosa. OBJECTIVE: Our purpose was to compare EBL (n = 9) with ETT (n = 13) for the treatment of bleeding from GAVE. DESIGN: Observational comparative study. PATIENTS: Patients with gastric antral vascular ectasia with occult or overt bleeding. SETTING: Mayo Clinic Arizona, a multispecialty academic medical center. INTERVENTION: EBL or ETT with argon plasma coagulation or electrocautery. MAIN OUTCOME AND MEASUREMENTS: Number of treatments to cessation of bleeding and posttreatment hemoglobin, hospitalization, and transfusion requirement. RESULTS: There were no significant differences in the demographics, clinical presentation, associated portal hypertension, or mean hemoglobin values or the mean number of transfusions or hospitalizations between the 2 groups before treatment. Four patients in the EBL group had failed prior ETT. Compared with ETT, in exploratory statistical testing EBL had a significantly higher rate of bleeding cessation (67% vs 23%, P = .04), fewer treatment sessions required for cessation of bleeding (1.9 vs 4.7, P = .05), a greater increase in hemoglobin values (2.8 g/dL vs 0.9 g/dL, P = .05), a greater decrease in transfusion requirements (-12.7 vs -5.2, P = .02), and a greater decrease in hospital admissions (-2.6 vs -0.5, P = .02) during the follow-up period. Analysis of covariance showed significantly superior efficacy of EBL for cessation of bleeding, postprocedure transfusion, and hospitalization. One patient in the EBL group had postprocedure emesis and 1 in the ETT group had immediate post procedure bleeding. All patients in the EBL group had complete mucosal healing with minimal residual GAVE at follow-up endoscopy failed post-EBL. CONCLUSIONS: Our initial experience suggests that EBL is superior to ETT for the management of GAVE. EBL required fewer treatment sessions for control of bleeding, had higher rates for cessation of bleeding, had a reduction in hospitalizations and transfusion requirements, and allowed for a significant increase in hemoglobin values.


Subject(s)
Electrocoagulation/methods , Gastric Antral Vascular Ectasia/complications , Gastrointestinal Hemorrhage/surgery , Gastroscopy/methods , Academic Medical Centers , Aged , Aged, 80 and over , Cohort Studies , Electrocoagulation/adverse effects , Female , Follow-Up Studies , Gastric Antral Vascular Ectasia/diagnosis , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/mortality , Gastroscopy/adverse effects , Hemostasis, Endoscopic/adverse effects , Hemostasis, Endoscopic/methods , Humans , Ligation/adverse effects , Ligation/methods , Male , Middle Aged , Probability , Retrospective Studies , Risk Assessment , Sensitivity and Specificity , Survival Rate , Treatment Outcome
18.
Am J Gastroenterol ; 103(3): 745-52, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18028510

ABSTRACT

Gastrointestinal endoscopy is an evolving field kindled by technologic advances, scientific discoveries, and the innovative minds of endoscopists. The development and subsequent applications of overtubes in gastrointestinal endoscopy mirror this larger evolution. In this article, we review the development, applications, and complications associated with overtubes in gastrointestinal endoscopy.


Subject(s)
Endoscopes, Gastrointestinal , Endoscopy, Gastrointestinal/methods , Endoscopes, Gastrointestinal/adverse effects , Endoscopy, Gastrointestinal/adverse effects , Foreign Bodies/diagnosis , Foreign Bodies/therapy , Gastrointestinal Tract , Humans
19.
BMC Gastroenterol ; 7: 19, 2007 Jun 08.
Article in English | MEDLINE | ID: mdl-17559669

ABSTRACT

BACKGROUND: Many factors impacting cecal intubation rates have been examined in detail; however, little information exists regarding the effect of the timing of the procedure. We sought to examine any difference in cecal intubation rates between morning and afternoon colonoscopies and identify factors contributing to a discrepancy. METHODS: Retrospective, single-center study comparing cecal intubation rates for colonoscopies performed in the morning (begun prior to 12 noon) and colonoscopies performed in the afternoon (begun after 12 noon) over an approximately 12 month period. Univariate and multivariate analyses were performed evaluating patient demographics, procedure indication(s), endoscopist, bowel preparation type and quality, and participation by a gastroenterology fellow. RESULTS: 6087 colonoscopies were evaluated in this study. Colonoscopies (n = 3729) performed in the morning were compared to colonoscopies performed in the afternoon (n = 2358). The crude completion rate to the cecum was 95.0% in the morning group while the completion rate to the cecum was 93.6% of the afternoon exams (p = 0.02). The morning colonoscopies had better bowel preparation quality (p < 0.001). The multivariate analyses demonstrated that gender, age, and bowel preparation quality impacted completion rates. After correcting for these factors, there was no significant difference in completion rates in the morning versus afternoon. CONCLUSION: Uncorrected cecal intubation rates were lower in the afternoon compared to the morning in outpatients undergoing colonoscopy. Bowel preparation quality was worse in the afternoon compared with the morning. Efforts at improving afternoon bowel preparation may improve the outcome of afternoon colonoscopies.


Subject(s)
Appointments and Schedules , Colonoscopy/methods , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cecum , Enema/methods , Female , Humans , Intubation, Gastrointestinal , Logistic Models , Male , Middle Aged , Polyethylene Glycols/therapeutic use , Sex Factors , Time Factors , Treatment Failure
20.
Pharmacotherapy ; 26(12): 1802-5, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17125441

ABSTRACT

A 61-year-old Caucasian woman was transported to the emergency department after intentionally ingesting several different prescription drugs. She had been found by her husband in an unconscious state with empty bottles of extended-release venlafaxine, extended-release nifedipine, sertraline, and atorvastatin. She was intubated in the emergency department and transferred to the intensive care unit. After 36 hours in the intensive care unit, she was stabilized and brought to a general medical ward. She later developed profound recurrent hypotension with systolic blood pressures ranging from 40-70 mm Hg and diastolic blood pressures of 0-40 mm Hg. She was readmitted to the intensive care unit, where a computed tomography scan revealed a mass in her stomach. A gastroenterology consultation was obtained, and an esophagogastroduodenoscopy (EGD) was performed, during which a large drug bezoar was discovered and removed. The drugs were identified as extended-release nifedipine with a few granules of extended-release venlafaxine. Unfortunately, the patient died 3 days after the EGD from multisystem organ failure related to the overdose. Clinicians who encounter drug overdoses should be aware of the possibility of drug bezoar formation and should consider endoscopic removal as a potential treatment option.


Subject(s)
Bezoars/etiology , Calcium Channel Blockers/poisoning , Nifedipine/poisoning , Stomach , Anticholesteremic Agents/administration & dosage , Antidepressive Agents/administration & dosage , Atorvastatin , Bezoars/diagnostic imaging , Calcium Channel Blockers/administration & dosage , Cyclohexanols/administration & dosage , Delayed-Action Preparations , Drug Overdose , Endoscopy, Digestive System , Fatal Outcome , Female , Heptanoic Acids/administration & dosage , Humans , Middle Aged , Nifedipine/administration & dosage , Pyrroles/administration & dosage , Radiography , Sertraline/administration & dosage , Stomach/diagnostic imaging , Venlafaxine Hydrochloride
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