Is the distal hyperplastic polyp a marker for proximal neoplasia?

CONTEXT: The current literature is unclear about the association between distal hyperplastic polyps and synchronous neoplasia (adenomatous polyps and cancer) in the proximal colon. OBJECTIVE: To estimate the prevalence of proximal neoplasia associated with distal hyperplastic polyps. DATA SOURCES: Database searches (medline and embase from 1966 to 2001) and manual search of the bibliographies of included and excluded studies, case reports, editorials, review articles, and textbooks of Gastroenterology. STUDY SELECTION: Studies describing the prevalence of proximal neoplasia in persons with distal hyperplastic polyps. DATA EXTRACTION: Demographics, clinical variables, study design, and prevalence of proximal neoplasia associated with various distal colorectal findings. DATA SYNTHESIS: Of 18 included studies, 12 involved asymptomatic individuals in which the pooled absolute risk of any proximal neoplasia associated with distal hyperplastic polyps was 25% (95% confidence interval [95% CI], 21% to 29%). In 4 studies where colonoscopy was performed irrespective of distal findings, the absolute risk was 21% (95% CI, 14% to 28%). The relative risk of finding any proximal neoplasia in persons with distal hyperplastic polyps was 1.3 (95% CI, 0.9 to 1.8) compared to those with no distal polyps. Among 6 studies of patients with symptoms or risk factors for neoplasia, the absolute risk of proximal neoplasia was 35% (95% CI, 32% to 39%) in persons with distal hyperplastic polyps. In 2 studies of screening colonoscopy, advanced proximal neoplasia (cancer, or a polyp with villous histology or severe dysplasia, or a tubular adenoma >/=1 cm) was present in 4% to 5% of persons with distal hyperplastic polyps, which was 1.5 to 2.6 times greater than in those with no distal polyps. CONCLUSIONS: In asymptomatic persons, a distal hyperplastic polyp is associated with a 21% to 25% risk for any proximal neoplasia and a 4% to 5% risk of advanced proximal neoplasia, and may justify examination of the proximal colon. Further study is needed to determine the risk of advanced proximal neoplasia associated with size and number of distal hyperplastic polyps.     

Prolonged Elevated Heart Rate is a Risk Factor for Adverse Cardiac Events and Poor Outcome after Subarachnoid Hemorrhage

Introduction

Sympathetic nervous system hyperactivity is common after subarachnoid hemorrhage (SAH). We sought to determine whether uncontrolled prolonged heart rate elevation is a risk factor for adverse cardiopulmonary events and poor outcome after SAH.

Methods

We prospectively studied 447 SAH patients between March 2006 and April 2012. Prior studies define prolonged elevated heart rate (PEHR) as heart rate >95 beats/min for >12 h. Major adverse cardiopulmonary events were documented according to the predefined criteria. Global outcome at 3 months was assessed with the modified Rankin Scale (mRS).

Results

175 (39 %) patients experienced PEHR. Nonwhite race/ethnicity, admission Hunt–Hess grade ≥4, elevated APACHE-2 physiological subscore, and modified Fisher score were significant admission predictors of PEHR, whereas documented pre-hospital beta-blocker use was protective. After controlling for admission Hunt–Hess grade, Cox regression using time-lagged covariates revealed that PEHR onset in the previous 48 h was associated with an increased hazard for delayed cerebral ischemia, myocardial injury, and pulmonary edema. PEHR was associated with 3-month poor outcome (mRS 4–6) after controlling for known predictors.

Conclusions

PEHR is associated with major adverse cardiopulmonary events and poor outcome after SAH. Further study is warranted to determine if early sympatholytic therapy targeted at sustained heart rate control can improve outcome after SAH.     

Risk and predictors of dyssynchrony cardiomyopathy in left bundle branch block with preserved left ventricular ejection fraction

BackgroundLeft bundle branch block (LBBB) and left ventricular (LV) dyssynchrony likely contribute to progressive systolic dysfunction. The evaluation of newly recognized LBBB includes screening for structural heart abnormalities and coronary artery disease (CAD). In patients whose LV ejection fraction (EF) is preserved during initial testing, the incidence of subsequent cardiomyopathy is not firmly established.HypothesisThe risk of developing LV systolic dysfunction among LBBB patients with preserved LVEF is high enough to warrant serial imaging.MethodsWe screened records of 1000 consecutive patients with LBBB from our ECG database and identified subjects with an initially preserved LVEF (≥45%) without clinically relevant CAD or other cause for cardiomyopathy. Baseline imaging, clinical data, and follow‐up imaging were recorded to determine the risk of subsequent LV systolic dysfunction (LVEF ≤40%).Results(Data are mean + SD) 784 subjects were excluded, the majority for CAD or depressed LVEF upon initial imaging. Of the remaining 216, 37 (17%) developed a decline in LVEF(≤40%) over a mean follow‐up of 55 ± 31 months; 94% of these patients had a baseline LVEF≤60% and LV end systolic diameter (ESD) ≥ 2.9 cm indicating that these measures may be useful to define which patients warrant longitudinal follow‐up. The negative predictive value of a LVEF>60% and LVESD <2.9 cm was 98%.ConclusionsSeventeen percent of patients with LBBB and initial preserved LVEF develop dyssynchrony cardiomyopathy. We believe the risk of developing dyssynchrony cardiomyopathy is high enough to warrant serial assessment of LV systolic function in this high‐risk population.     

Atrial synchronous left ventricular only pacing with VDD pacemaker system – A cost effective alternative to conventional cardiac resynchronization therapy

Introduction

Atrial synchronous left ventricular (LV) only pacing using two leads and VDD pacemaker could be a cost effective alternative to conventional cardiac resynchronization therapy (CRT).

Methods

We implanted right atrial (RA) and LV leads with VDD pulse generator (LV only pacing) in five carefully screened heart failure patients who could not afford conventional CRT. All had NYHA class III/IV symptoms despite maximal guideline directed medical therapy. The sensed atrioventricular delay was programmed to pre-excite the LV and achieve fusion beat. Response to treatment was assessed at 6 months.

Results

Four patients were males. The mean age was 58 ± 12 years. At follow up, there was improvement in electrocardiographic, and echocardiographic parameters: Mean QRS duration decreased from 174 ± 17 msec to 128 ± 10.9 msec (p = 0.009), LV end-diastolic diameter decreased from 73.2 ± 12 mm to 65.8 ± 9.6 mm (p = 0.026), LV end-systolic diameter decreased from 65 ± 12 mm to 54 ± 10 mm (p = 0.020). There was a trend towards reduction of LV end-systolic and end-diastolic volumes. LV ejection fraction improved from 25 ± 6% to 34 ± 6% (p = 0.013) and left atrial dimension reduced from 44 ± 4 mm to 39 ± 5 mm (p = 0.045). All patients improved clinically.

Conclusion

RA-LV pacing using VDD pacemaker is a safe and effective technique of CRT. This may be a cost effective alternative to conventional CRT for patients in developing countries.     

Silencing of a metaphase I-specific gene results in a phenotype similar to that of the Pairing homeologous 1 (Ph1) gene mutations

Although studied extensively since 1958, the molecular mode of action of the Pairing homeologous 1 (Ph1) gene is still unknown. In polyploid wheat, the diploid-like chromosome pairing is principally controlled by the Ph1 gene via preventing homeologous chromosome pairing (HECP). Here, we report a candidate Ph1 gene (C-Ph1) present in the Ph1 locus, transient as well as stable silencing of which resulted in a phenotype characteristic of the Ph1 gene mutants, including HECP, multivalent formation, and disrupted chromosome alignment on the metaphase I (MI) plate. Despite a highly conserved DNA sequence, the C-Ph1 gene homeologues showed a dramatically different structure and expression pattern, with only the 5B copy showing MI-specific expression, further supporting our claim for the Ph1 gene. In agreement with the previous reports about the Ph1 gene, the predicted protein of the 5A copy of the C-Ph1 gene is truncated, and thus perhaps less effective. The 5D copy is expressed around the onset of meiosis; thus, it may function during the earlier stages of chromosome pairing. Along with alternate splicing, the predicted protein of the 5B copy is different from the protein of the other two copies because of an insertion. These structural and expression differences among the homeologues concurred with the previous observations about Ph1 gene function. Stable RNAi silencing of the wheat gene in Arabidopsis showed multivalents and centromere clustering during meiosis I.The Pairing homeologous 1 (Ph1) gene was discovered in 1958 based on the observation that plants lacking wheat chromosome 5B exhibit homeologous pairing (1, 2). Lack of the gene results in multivalents during metaphase I (MI) of meiosis, resulting in partial sterility. Conversely, six doses of the gene in the triisosomic line of chromosome 5BL resulted in interlocking of the bivalents and reduced chiasmata frequency even among homologs, along with rare multivalents (3). Several other genes promoting or suppressing homeologous chromosome pairing (HECP) have also been reported (4, 5), although their effect is difficult to measure in the presence of the Ph1 gene (6). Ph1-like genes were also reported in other sexually propagating polyploids, including Avena sativa, Festuca arundinacea, Brassica napus, Gossypium hirsutum, and Gossypium barbadense, as well as in some diploids, including Lolium perenne, Lolium multiflorum, and Lolium rigidum (7–11).Ph1 gene mutants in tetraploid (ph1c) (12, 13) and hexaploid (ph1b) (14) wheat were shown to be interstitial deletions involving an ∼0.84-μm region and an ∼1.05-μm region around the gene, respectively (15, 16) (SI Appendix, Fig. S1). Physical mapping localized the gene to an ∼2.5-Mb chromosomal region referred to as “Ph1 gene region,” bracketed by the distal breakpoint of ph1c deletion on the distal end and the breakpoint of deletion line 5BL-1 on the proximal end (16) (SI Appendix, Fig. S1). Various marker enrichment efforts identified nine markers for the region (17). Detailed microsynteny analyses and comparative mapping identified a 450-kb region of rice chromosome 9 (17). The corresponding rice region contained 91 genes. The major objective of the present study is to identify the gene(s) responsible for the Ph1 gene-like function using the available mapping information.     

Neonatal Gastric Perforations: Are They Really Spontaneous?

Case Report

We report a case of 4-day-old male infant who developed rapid abdominal distension with progression to shock. Abdominal radiography showed free gas under diaphragm for which emergency laparotomy was done revealing a perforation in the greater curvature of the stomach that was sutured after excising surrounding ischemic stomach wall.     

Copolymers of bipyridinium and metal (Zn & Ni) porphyrin derivatives; theoretical insights and electrochemical activity towards CO2

This study reports the electropolymerization of novel keto functionalized octaethyl metal porphyrins (Zn²⁺ and Ni²⁺) in the presence of 4,4′-bipyridine (4,4′-bpy) as a bridging nucleophile. The polymer films were characterized by electrochemical, spectroscopic (UV-Vis, XPS, FT-IR and Raman spectroscopy) and imaging (AFM and SEM) techniques. The absorption and electronic spectra confirm the presence of both porphyrin and 4,4′-bipyridine units in the film. The surface morphology reveals homogeneous film deposition with average roughness values of approx. 8 nm. The theoretical studies performed offered insights into the interplay of different metal centres (Zn²⁺ and Ni²⁺) and the keto functionality of the porphyrin unit in the formation of copolymer films. The electrochemical interaction of polymer films with CO₂ suggests a reversible trap and release of CO₂ with low energy barriers for both the polymers.

Electropolymerization of keto functionalized porphyrins and 4,4′-bipyridine.