Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett’s Esophagus

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H. pylori infection and genotyping in patients undergoing upper endoscopy at inner city hospitals

Kings County Hospital (KCH), and St. John's Episcopal Hospital (SJH) are inner-city hospitals in New York City serving predominantly minority populations. Staten Island University Hospital (SIUH) serves a predominantly middle-class Caucasian population. We examined H. pylori (HP) infection in patients undergoing upper endoscopy at these hospitals. Two gastric biopsies were obtained from each patient. One biopsy was examined by histology or the rapid urease test for the presence of HP. The other was subjected to analysis by PCR to detect HP DNA and to identify putative HP virulence factors. Of 200 subjects, 54% were African-American, 10% were Hispanic, and 36% were Caucasian. HP infection rates in African-American, Hispanic, and Caucasian patients were 43%, 20%, and 11%, respectively. Many of the African-American patients are recent immigrants from the Caribbean Islands. In these patients, an inverse relationship was observed between HP infection and the number of years living in the United States. Higher levels of HP infection were observed in patients with duodenitis and peptic ulcer disease. With respect to HP virulence factors, the vacA s1b and m1 alleles, as well as the iceA2 allele were the predominant alleles expressed in HP-positive samples obtained from African-Americans. The cagA gene was detected in 81% of HP-positive samples. However, CagA positivity was not related to any specific gastrointestinal disorder. Our findings indicate that among several ethnic groups served by three hospitals, African-American patients have the highest rate of HP infection. Moreover, in African-American patients undergoing endoscopy: (1) HP infection was inversely related to the number of years the patients have been living in the USA; (2) HP infection rates were higher in patients diagnosed with duodenitis and peptic ulcer disease versus other disorders; (3) expression of the CagA gene was not associated with any specific gastroduodenal disorder; and (4) there was little allelic heterogeneity with respect to VacA and IceA subtypes. These findings suggest that inner-city African-Americans are more likely to be infected with HP and suffer from more serious gastroduodenal disorders than other ethnic groups.     

Long-term outcome of rubber band ligation for symptomatic primary and recurrent internal hemorrhoids

PURPOSE: Rubber band ligation therapy for symptomatic hemorrhoidal disease has been used for many years and is a well-accepted treatment modality, but information on long-term outcome is limited. Our goals were to determine safety and long-term efficacy of this treatment.METHODS: A retrospective chart review of patients undergoing rubber band ligatures for symptomatic internal hemorrhoids in a single practice was conducted. Information on presenting symptoms, number of bands applied, response to therapy, complications encountered, length of follow-up, interval to recurrent symptoms when applicable, and subsequent therapy were documented. Supplemental information was obtained from telephone follow-up. Outcome was categorized as success or failure, in which success was defined as: permanent relief of symptoms for follow-up period; marked improvement in symptomatology with rare manifestation of bleeding (1/month); symptom relief for a limited period of time (100 days), and failure was defined as: modest improvement (decreased but not relief of symptoms); or no improvement in symptoms.RESULTS: A total of 805 patients underwent 2,114 rubber band ligatures. Most common presenting symptoms were bleeding in 731 patients (90.8 percent) and prolapsing in 382 patients (47.5 percent). The median number of bands placed was two (range, 1–17). The median time between bandings was 4.7 (range, 1.1–35.6) weeks. Median follow-up time was 1,204 (range, 14–9,571) days. Excluding 104 patients lost to follow-up (never returned after initial treatment), success was obtained in 70.5 percent (494/701) and failure in 29.5 percent (207/701) of patients. Success rates were similar for all degrees of hemorrhoids. Hemorrhoidal disease requiring the placement of four or more bands was associated with a trend in higher failure rates and greater need for subsequent hemorrhoidectomy. Complications per treatment series included bleeding (2.8 percent), thrombosed external hemorrhoids (1.5 percent), and bacteremia (0.09 percent). Higher bleeding rates were encountered with the use of acetylsalicylic acid/nonsteroidal anti-inflammatory drugs and warfarin. Time to recurrence was less with subsequent treatment courses. Treatment of recurrent symptoms with rubber band ligation resulted in success rates of 73.6, 61.4, and 65 percent for first, second, and third recurrences respectively. This resulted in a cumulative success rate of 80.2 percent for this method of treatment.CONCLUSIONS: Rubber band ligatures are safe and effective therapy for symptomatic internal hemorrhoids. It can be used to treat all degrees of hemorrhoids with similar effectiveness. The likelihood of success is lower if more than four bands are needed to eliminate symptoms. The use of acetylsalicylic acid/nonsteroidal anti-inflammatory drugs and warfarin is associated with higher bleeding rates. Rubber band ligatures for recurrence of symptoms is effective; however, time to recurrence is less with subsequent treatments.Read at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

Regional desensitization of beta-adrenergic receptor signaling in swine with chronic hibernating myocardium

Contractile reserve during submaximal beta-adrenergic stimulation is attenuated in patients and swine with hibernating myocardium. We tested the hypothesis that this arises as a regional adaptive response in beta-adrenergic adenylyl cyclase coupling. Pigs (n=8) were studied 3 months after instrumentation with a left anterior descending artery (LAD) stenosis when flow (LAD, 0.7+/-0.2 versus 1.2+/-0.1 mL/min per gram in normal remote; P<0.05) and wall thickening (LAD, 15.5 [corrected]+/-3.2% versus 40.0+/-5.5% in remote; P<0.05) were reduced in the absence of infarction. Whereas basal cAMP production was normal (LAD, 87+/-18 versus 91+/-19 pmol/mg per minute; P=NS), responses to isoproterenol were blunted (LAD, 83+/-6 versus 146+/-25 pmol/mg per minute in remote; P<0.05). beta-receptor density and subtype were unchanged, but there was a reduction in the number of high-affinity binding sites (LAD, 40+/-4% versus 53+/-7% in normal remote; P<0.05). The Gialpha2/Gsalpha ratio increased (LAD, 1.8+/-0.3 versus 0.99+/-0.3 in remote myocardium; P<0.05), although GppNHp-stimulated cAMP production was equivocally reduced. Forskolin responses were unchanged and similar to shams. These data indicate regional attenuation of beta-receptor adenylyl cyclase signaling in hibernating myocardium. This blunts the local contractile response to beta-adrenergic stimulation and may serve to protect against a myocardial supply/demand imbalance when external determinants of myocardial workload increase during sympathetic activation.     

Maximum urine concentrating ability in children with Hb SC disease: effects of hydroxyurea

Studies in adults with Hb SC disease suggested that hydroxyurea reduced hemolysis and increased red cell hydration. Because increased hydration should diminish the polymerization tendency of Hb S we hypothesized that hydroxyurea might repair the urine concentration defect of HbSC disease. Eight Hb SC disease patients, aged 10 to 17 years, were given hydroxyurea daily. Maximal urine concentrating ability following overnight fasting and after subcutaneous arginine vasopressin (dDAVP), blood counts, and cell volumes were observed for 12-15 months. All patients had impaired urine concentrating ability prior to hydroxyurea treatment and failed to increase their ability to concentrate urine following treatment (maximum urine concentration after an overnight fast and dDAVP, 520-530 mOsm). Mean corpuscular volume (MCV) and reticulocyte MCV increased after administration of hydroxyurea, and the reticulocyte count and ratio of red cell hemoglobin to reticulocyte hemoglobin fell but there was little change in PCV. Hb F increased substantially in 2 patients but showed little change in the remaining patients. There was no evidence that hydroxyurea was associated with increased urine concentrating ability in children with Hb SC disease. These results may reflect irreversible renal medullary damage prior to beginning treatment or insufficient intensity or duration of treatment.     

Mitral regurgitation in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: prognostic significance and relation to ventricular size and function.

AIMS: Mitral regurgitation (MR) confers independent risk in patients with acute myocardial infarction. We utilized data from the VALsartan In Acute myocardial iNfarcTion echo study to relate baseline MR to left ventricular (LV) size, shape, and function, and to assess the relationship between baseline MR and progression of MR and cardiovascular (CV) outcomes. METHODS AND RESULTS: We studied 496 patients with heart failure (HF) and/or systolic dysfunction after MI who underwent echocardiography at a median of 5 days after MI. MR severity, quantified as the regurgitant jet area/left atrial area ratio, was assessed at baseline, one and 20 months post-MI and related to LV size, shape, function, and clinical outcomes. Increased MR at baseline was associated with larger LV end-diastolic and end-systolic volumes, increased sphericity index, and reduced ejection fraction (P trend < 0.001). Moderate-severe MR was an independent predictor of total mortality [adjusted hazard ratio (HR) 2.4 (1.1-5.3)], CV mortality [adjusted HR 2.7 (1.2-6.1)], hospitalization for HF [adjusted HR 2.5 (1.1-5.5)], or death or HF hospitalization [adjusted HR 2.5 (1.4-4.6)]. Patients with progression of MR during the first post-MI month were substantially more likely to die or develop HF (adjusted HR per increased MR grade 3.0, 95% CI 1.8-4.9). Progression of MR over 20 months in survivors was associated with increased hospitalizations for HF (P < 0.001). CONCLUSION: Following high-risk myocardial infarction, baseline mitral regurgitant severity is associated with larger LV volumes and worse LV function. Both baseline MR severity and progression of MR are associated with an increased likelihood of adverse outcomes.     

Neuroarchitecture and neuroanatomy of the Drosophila central complex: A GAL4‐based dissection of protocerebral bridge neurons and circuits

Insects exhibit an elaborate repertoire of behaviors in response to environmental stimuli. The central complex plays a key role in combining various modalities of sensory information with an insect's internal state and past experience to select appropriate responses. Progress has been made in understanding the broad spectrum of outputs from the central complex neuropils and circuits involved in numerous behaviors. Many resident neurons have also been identified. However, the specific roles of these intricate structures and the functional connections between them remain largely obscure. Significant gains rely on obtaining a comprehensive catalog of the neurons and associated GAL4 lines that arborize within these brain regions, and on mapping neuronal pathways connecting these structures. To this end, small populations of neurons in the Drosophila melanogaster central complex were stochastically labeled using the multicolor flip‐out technique and a catalog was created of the neurons, their morphologies, trajectories, relative arrangements, and corresponding GAL4 lines. This report focuses on one structure of the central complex, the protocerebral bridge, and identifies just 17 morphologically distinct cell types that arborize in this structure. This work also provides new insights into the anatomical structure of the four components of the central complex and its accessory neuropils. Most strikingly, we found that the protocerebral bridge contains 18 glomeruli, not 16, as previously believed. Revised wiring diagrams that take into account this updated architectural design are presented. This updated map of the Drosophila central complex will facilitate a deeper behavioral and physiological dissection of this sophisticated set of structures. J. Comp. Neurol. 523:997–1037, 2015. © 2014 Wiley Periodicals, Inc.