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1.  Blue Rubber Bleb Nevus Syndrome as a Cause of Lower Digestive Bleeding 
Case Reports in Surgery  2014;2014:683684.
Introduction. Blue rubber bleb nevus syndrome is a rare disorder that is characterized by multiple recurrent vascular malformations that involve the skin and the gastrointestinal tract. The disease can present chronic anemia and severe episodes of gastrointestinal bleeding. Case Report. A 41-year-old man was admitted with recurrent episodes of lower gastrointestinal bleeding and anemia that had worsened over the last 3 months. The physical examination showed soft, diffuse, compressible, bluish nodules on all of the skin surfaces of the body. A biopsy from one of these skin lesions allowed a histological diagnosis of cavernous hemangioma. He submitted to a colonoscopy, which showed hemorrhoids and a plane vascular lesion mainly located on the right colon with recent signs of bleeding; this lesion was treated by local excision and sclerosis. The pathological study of the colon specimens also reflected the presence of cavernous hemangioma. The cutaneous hemangiomas and the presence of colonic venous malformations were compatible with blue rubber bleb nevus syndrome. The patient presented a favorable follow-up with clinical control of the anemia and without relapse of the gastrointestinal bleeding two years after the procedure. Conclusion. Although rarely diagnosed, blue rubber bleb nevus syndrome may be responsible for lower digestive bleeding.
PMCID: PMC3932640  PMID: 24653853
2.  Taking Healthy Steps: rationale, design and baseline characteristics of a randomized trial of a pedometer-based internet-mediated walking program in veterans with chronic obstructive pulmonary disease 
Low levels of physical activity are common in patients with chronic obstructive pulmonary disease (COPD), and a sedentary lifestyle is associated with poor outcomes including increased mortality, frequent hospitalizations, and poor health-related quality of life. Internet-mediated physical activity interventions may increase physical activity and improve health outcomes in persons with COPD.
This manuscript describes the design and rationale of a randomized controlled trial that tests the effectiveness of Taking Healthy Steps, an Internet-mediated walking program for Veterans with COPD. Taking Healthy Steps includes an uploading pedometer, a website, and an online community. Eligible and consented patients wear a pedometer to obtain one week of baseline data and then are randomized on a 2:1 ratio to Taking Healthy Steps or to a wait list control. The intervention arm receives iterative step-count feedback; individualized step-count goals, motivational and informational messages, and access to an online community. Wait list controls are notified that they are enrolled, but that their intervention will start in one year; however, they keep the pedometer and have access to a static webpage.
Participants include 239 Veterans (mean age 66.7 years, 93.7% male) with 155 randomized to Taking Healthy Steps and 84 to the wait list control arm; rural-living (45.2%); ever-smokers (93.3%); and current smokers (25.1%). Baseline mean St. George’s Respiratory Questionnaire Total Score was 46.0; 30.5% reported severe dyspnea; and the average number of comorbid conditions was 4.9. Mean baseline daily step counts was 3497 (+/- 2220).
Veterans with COPD can be recruited to participate in an online walking program. We successfully recruited a cohort of older Veterans with a significant level of disability including Veterans who live in rural areas using a remote national recruitment strategy.
Trial registration
Clinical NCT01102777
PMCID: PMC3946238  PMID: 24491137
COPD; Chronic bronchitis; Emphysema; Quality of life; Exercise; Physical activity; Internet; Pedometer; Walking; Veterans
3.  Neuromyelitis Optica in Child: Diagnostic and Therapeutic Challenges 
Case Reports in Pediatrics  2013;2013:124929.
Neuromyelitis optica (NMO) is a rare syndrome of severe inflammatory demyelination of the central nervous system, causing attacks of optic neuritis and transverse myelitis. Although uncommon, attention should be given to the proper identification and management of the affected patients. We present a case of a 13-year-old girl with severe neuromyelitis optica. The patient's initial presentation consisted of encephalopathy and optic neuritis. Approximately 2 months later, coinciding with the weaning of steroid treatment, she presented with ascending paralysis and respiratory failure. She was seropositive for NMO-IgG. Treatment included intravenous immune globulin, steroids, plasmapheresis, and rituximab and was complemented with proper nutrition, vitamins, minerals, and intense rehabilitation. Two years after the initial presentation and one short relapse, the patient has made a remarkable recovery without neurologic deficit. This report underscores the difficulty in making the initial diagnosis, choosing the best treatment, and the need for more streamlined pediatric guidelines for diagnosis, treatment, and prevention of relapses of pediatric NMO.
PMCID: PMC3874358  PMID: 24392237
4.  Gender Differences in Symptoms and Care Delivery for Chronic Obstructive Pulmonary Disease 
Journal of Women's Health  2012;21(12):1267-1274.
Morbidity and mortality for women with chronic obstructive pulmonary disease (COPD) are increasing, and little is known about gender differences in perception of COPD care.
Surveys were administered to a convenience sample of COPD patients to evaluate perceptions about symptoms, barriers to care, and sources of information about COPD.
Data on 295 female and 273 male participants were analyzed. With similar frequencies, women and men reported dyspnea and rated their health as poor/very poor. Although more women than men reported annual household income <$30,000, no significant gender differences in frequency of health insurance, physician visits, or ever having had spirometry were detected. In adjusted models (1) women were more likely to report COPD diagnostic delay (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.13-2.45, p=0.01), although anxiety (OR 1.83, 95% CI 1.10-3.06, p=0.02) and history of exacerbations (OR 1.60, 95% CI 1.08-2.37, p=0.01) were also significant predictors, (2) female gender was associated with difficulty reaching one's physician (OR 2.54, 95% CI 1.33-4.86, p=0.004), as was prior history of exacerbations (OR 2.25, 95% CI 1.21-4.20, p=0.01), and (3) female gender (OR 2.15, 95% CI 1.10-4.21, p=0.02) was the only significant predictor for finding time spent with their physician as insufficient.
Significant gender-related differences in the perception of COPD healthcare delivery exist, revealing an opportunity to better understand what influences these attitudes and to improve care for both men and women.
PMCID: PMC3518541  PMID: 23210491
5.  Oximetry Signal Processing Identifies REM Sleep-Related Vulnerability Trait in Asthmatic Children 
Sleep Disorders  2013;2013:406157.
Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA. Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n = 134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance level P ≤ 0.05). Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, (2) the maximal % of SaO2 desaturation during REM, but not during NREM, was significantly higher in asthmatic children, and (3) multivariate analysis revealed that the association between asthma and REM-related maximal % SaO2 desaturation was independent of demographic variables. Conclusion. These results demonstrate that children with asthma have a REM-related vulnerability trait that impacts oxygenation independently of OSA. Further research is needed to delineate the REM sleep neurobiological mechanisms that modulate the phenotypical expression of nocturnal asthma in children.
PMCID: PMC3832976  PMID: 24288619
6.  Relationship between Quantitative CT Metrics and Health Status and Bode in COPD 
Thorax  2012;67(5):399-406.
The value of quantitative computed tomography (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. We hypothesized that QCT-defined emphysema and airway abnormalities relate to St. George's Respiratory Questionnaire (SGRQ) and BODE.
1,200 COPDGene subjects meeting GOLD criteria for COPD with QCT analysis were included. Total lung emphysema was measured using density mask technique with a -950 HU threshold. An automated program measured mean wall thickness (WT), wall area percent (WA%) and pi10 in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.
In separate models predicting SGRQ score, a one unit standard deviation (SD) increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p<0.001). The comparable increase in SGRQ for a one unit SD increase in percent emphysema in these models was relatively weaker, significant only in the pi10 model (for percent emphysema, 1.45 points higher, p=0.01). In separate models predicting BODE, a one unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07 fold increase, p<0.001; for WA%, 1.20 fold increase, p<0.001; for pi10, 1.16 fold increase, p<0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26 fold increase, p<0.001).
Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.
PMCID: PMC3719874  PMID: 22514236
Imaging; COPD; emphysema
7.  Gene Silencing Activity of siRNA Molecules Containing Phosphorodithioate Substitutions 
ACS Chemical Biology  2012;7(7):1214-1220.
Chemically synthesized small interfering RNAs (siRNAs) have been widely used to identify gene function and hold great potential in providing a new class of therapeutics. Chemical modifications are desired for therapeutic applications to improve siRNA efficacy. Appropriately protected ribonucleoside-3′-yl S-[β-(benzoylmercapto)ethyl] pyrrolidinothiophosphoramidite monomers were prepared for the synthesis of siRNA containing phosphorodithioate (PS2) substitutions in which the two non-bridging oxygen atoms are replaced by sulfur atoms. A series of siRNAs containing PS2 substitutions have been strategically designed, synthesized and evaluated for their gene silencing activities. These PS2-siRNA duplexes exhibit an A-form helical structure similar to unmodified siRNA. The effect of PS2 substitutions on gene silencing activity is position-dependent, with certain PS2-siRNAs showing significantly higher activity than unmodified siRNA. The relative gene silencing activities of siRNAs containing either PS2 or phosphoromonothioate (PS) linkages at identical positions are variable and depend on the sites of modification. 5′-Phosphorylation of PS2-siRNAs has little or no effect on gene silencing activity. Incorporation of PS2 substitutions into siRNA duplexes increases their serum stability. These results offer preliminary evidence of the potential value of PS2 modified siRNAs.
PMCID: PMC3401229  PMID: 22512638
8.  Rearrangements of 2.5 Kilobases of Noncoding DNA from the Drosophila even-skipped Locus Define Predictive Rules of Genomic cis-Regulatory Logic 
PLoS Genetics  2013;9(2):e1003243.
Rearrangements of about 2.5 kilobases of regulatory DNA located 5′ of the transcription start site of the Drosophila even-skipped locus generate large-scale changes in the expression of even-skipped stripes 2, 3, and 7. The most radical effects are generated by juxtaposing the minimal stripe enhancers MSE2 and MSE3 for stripes 2 and 3 with and without small “spacer” segments less than 360 bp in length. We placed these fusion constructs in a targeted transformation site and obtained quantitative expression data for these transformants together with their controlling transcription factors at cellular resolution. These data demonstrated that the rearrangements can alter expression levels in stripe 2 and the 2–3 interstripe by a factor of more than 10. We reasoned that this behavior would place tight constraints on possible rules of genomic cis-regulatory logic. To find these constraints, we confronted our new expression data together with previously obtained data on other constructs with a computational model. The model contained representations of thermodynamic protein–DNA interactions including steric interference and cooperative binding, short-range repression, direct repression, activation, and coactivation. The model was highly constrained by the training data, which it described within the limits of experimental error. The model, so constrained, was able to correctly predict expression patterns driven by enhancers for other Drosophila genes; even-skipped enhancers not included in the training set; stripe 2, 3, and 7 enhancers from various Drosophilid and Sepsid species; and long segments of even-skipped regulatory DNA that contain multiple enhancers. The model further demonstrated that elevated expression driven by a fusion of MSE2 and MSE3 was a consequence of the recruitment of a portion of MSE3 to become a functional component of MSE2, demonstrating that cis-regulatory “elements” are not elementary objects.
Author Summary
Metazoan genes, including those of humans, contain large noncoding regions that are required for viability. Sequence variations in these regions are statistically associated with human disease, but the mechanisms underlying these associations are not well understood. These regions regulate transcription and are frequently larger than the gene's transcript by an order of magnitude. In this paper we attempt to elucidate the regulatory code of these noncoding segments of DNA by means of quantitative spatially resolved gene expression data and a computational model. The expression data comes from the early embryo of the fruit fly Drosophila melanogaster. We chose a family of DNA constructs to analyze that drive very different patterns of expression when very small changes in DNA sequence are made, reasoning that this sensitivity would reveal important properties of the regulatory code. The model reproduced the training data with precision greater than the expected accuracy of the training data itself. It was able to correctly predict from DNA sequence the expression of 44 segments of DNA from many genes and species.
PMCID: PMC3585115  PMID: 23468638
9.  Gallbladder-associated ectopic liver: A rare finding during a laparoscopic cholecystectomy 
Ectopic hepatic tissue is due to an uncommon failure of embryological liver development that is rarely described in the world medical literature. The incidence of ectopic liver (EL) has been reported to be anywhere from 0.24% to 0.47% as diagnosed at laparotomy or laparoscopy. We describe a case of EL adherent to the gallbladder, removed at laparoscopic cholecystectomy.
A 37-year-old female was admitted for elective cholecystectomy having had an episode of acute cholecystitis provoked by gallstones. During the procedure, a 30 mm × 10 mm × 5 mm section of EL tissue attached to the anterior wall of the gallbladder was identified and removed by en-bloc excision during laparoscopic cholecystectomy. Histological examination confirmed the absence of malignant degeneration of the hepatic tissue. The patient recovered well postoperatively and was discharged the day after the operation. She was well when seen six months later.
EL has been reported in several sites, such as the gallbladder, gastrohepatic ligament, adrenal glands, esophagus, and thoracic cavity. EL is often clinically silent and discovered incidentally during abdominal surgical procedures or autopsies. Because patients with ectopic liver may suffer complications such as torsion, peritoneal bleeding, fatty change, and evolution to cirrhosis or malignant degeneration to hepatocellular carcinoma, any ectopic liver tissue needs to be correctly identified and removed.
Despite the rare occurrence of EL, it should be recognized and removed by the surgeon to prevent a higher risk of complications and malignant transformation.
PMCID: PMC3604663  PMID: 23399516
Ectopic liver; Choristoma; Liver heterotopia; Laparoscopic
10.  Trends in the prevalence of antipsychotic drug use among patients with Alzheimer's disease and other dementias including those treated with antidementia drugs in the community in the UK: a cohort study 
BMJ Open  2013;3(1):e002080.
To investigate the pattern and trends of use of antipsychotics, antidepressants, hypnotics and anxiolytics in Alzheimer's disease and other dementias and in patients treated with antidementia medications.
Cohort study with dementia patients formed in the UK Clinical Practice Research Datalink. Participants Patients with incident dementia, between 1995 and 2011 and a reference non-dementia cohort matched on age, gender and date of dementia diagnosis. Two subcohorts included new users of acetylcholinesterase inhibitors (AChEIs) and memantine. The study endpoint was use of antipsychotics, antidepressants, hypnotics and anxiolytics up to 10 years before and 4 years after dementia diagnosis, and for up to 5 years before and 1 year after first use of AChEI or memantine.
50 349 patients with incident dementia diagnosis and 50 349 matched controls, 10 794 first-time users of AChEI and 669 of memantine. The mean prevalence of antipsychotic use from 1995 to 2011 on diagnosis of dementia was 12.5%, decreasing from 19.9% in 1995 to 7.4% in 2011. There was an increase in antidepressant use (10.7–26.3%) and a small increase in anxiolytic use. The matched cohort showed a lower use of antipsychotics and anxiolytics but a rise in antidepressants (5.9–13.4%). Both groups showed a decrease in hypnotic use. 10.6% of AChEI and 26.3% of memantine users were prescribed antipsychotics, 34.1% and 26.3% antidepressants, 13.2% and 4.1% anxiolytics and 18.4% and 8.3% hypnotics. The slopes for monthly use of antipsychotics were positive in the year leading up to AChEI and memantine use; after treatment initiation the slope for AChEI users continued to increase but at a reduced rate whereas antipsychotic use declined for memantine users.
The marked reduction in antipsychotic use in dementia is to be welcomed while there was a steady increase in antidepressant use. There was a decline in antipsychotic use after the initiation of memantine.
PMCID: PMC3549220  PMID: 23299113
11.  Abdominal Adiposity Correlates with Adenotonsillectomy Outcome in Obese Adolescents with Severe Obstructive Sleep Apnea 
Pulmonary Medicine  2012;2012:351037.
Background. Obese adolescents with Obstructive Sleep Apnea (OSA) have a unique pathophysiology that combines adenotonsillar hypertrophy and increased visceral fat distribution. We hypothesized that in this population waist circumference (WC), as a clinical marker of abdominal fat distribution, correlates with the likelihood of response to AT. Methods. We conducted a retrospective cohort study of obese adolescents (BMI ≥ 97th percentile) that underwent AT for therapy of severe OSA (n = 21). We contrasted WC and covariates in a group of subjects that had complete resolution of severe OSA after AT (n = 7) with those obtained in subjects with residual OSA after AT (n = 14). Multivariate linear and logistic models were built to control possible confounders. Results. WC correlated negatively with a positive AT response in young adolescents and the percentage of improvement in obstructive apnea-hypopnea index (OAHI) after AT (P ≤ 0.01). Extended multivariate analysis demonstrated that the link between WC and AT response was independent of demographic variables, OSA severity, clinical upper airway assessment, obesity severity (BMI), and neck circumference (NC). Conclusion. The results suggest that in obese adolescents, abdominal fat distribution determined by WC may be a useful clinical predictor for residual OSA after AT.
PMCID: PMC3518792  PMID: 23251797
12.  Diospyrobezoar as a Cause of Small Bowel Obstruction 
Case Reports in Gastroenterology  2012;6(3):596-603.
Phytobezoar, a concretion of indigestible fibers derived from ingested vegetables and fruits, is the most common type of bezoar. Diospyrobezoar is a subtype of phytobezoar formed after excessive intake of persimmons (Diospyros kaki). We report the case of a diabetic man with a 5-day history of abdominal pain after massive ingestion of persimmons who developed signs of complicated small bowel obstruction. The patient had a previous history of Billroth II hemigastrectomy associated with truncal vagotomy to treat a chronic duodenal ulcer 14 years earlier. Since intestinal obstruction was suspected, he underwent emergency laparotomy that revealed an ileal obstruction with small bowel perforation and local peritonitis due to a phytobezoar that was impacted 15 cm above the ileocecal valve. After segmental intestinal resection, the patient had a good recovery and was discharged on the 6th postoperative day. This report provides evidence that diospyrobezoar should be considered as a possible cause of small bowel obstruction in patients who have previously undergone gastric surgery.
PMCID: PMC3529578  PMID: 23271989
Bezoars; Diospyros kaki; Persimmon; Intestinal obstruction; Operative surgical procedure
13.  The freetext matching algorithm: a computer program to extract diagnoses and causes of death from unstructured text in electronic health records 
Electronic health records are invaluable for medical research, but much information is stored as free text rather than in a coded form. For example, in the UK General Practice Research Database (GPRD), causes of death and test results are sometimes recorded only in free text. Free text can be difficult to use for research if it requires time-consuming manual review. Our aim was to develop an automated method for extracting coded information from free text in electronic patient records.
We reviewed the electronic patient records in GPRD of a random sample of 3310 patients who died in 2001, to identify the cause of death. We developed a computer program called the Freetext Matching Algorithm (FMA) to map diagnoses in text to the Read Clinical Terminology. The program uses lookup tables of synonyms and phrase patterns to identify diagnoses, dates and selected test results. We tested it on two random samples of free text from GPRD (1000 texts associated with death in 2001, and 1000 general texts from cases and controls in a coronary artery disease study), comparing the output to the U.S. National Library of Medicine’s MetaMap program and the gold standard of manual review.
Among 3310 patients registered in the GPRD who died in 2001, the cause of death was recorded in coded form in 38.1% of patients, and in the free text alone in 19.4%. On the 1000 texts associated with death, FMA coded 683 of the 735 positive diagnoses, with precision (positive predictive value) 98.4% (95% confidence interval (CI) 97.2, 99.2) and recall (sensitivity) 92.9% (95% CI 90.8, 94.7). On the general sample, FMA detected 346 of the 447 positive diagnoses, with precision 91.5% (95% CI 88.3, 94.1) and recall 77.4% (95% CI 73.2, 81.2), which was similar to MetaMap.
We have developed an algorithm to extract coded information from free text in GP records with good precision. It may facilitate research using free text in electronic patient records, particularly for extracting the cause of death.
PMCID: PMC3483188  PMID: 22870911
14.  Volvulus of the Sigmoid Colon during Pregnancy: A Case Report 
Colonic obstruction due to sigmoid colon volvulus during pregnancy is a rare but complication with significant maternal and fetal mortality. We describe a case of sigmoid volvulus in a patient with 33 weeks of gestation that developed complete necrosis of the left colon. Case. 27-year-old woman was admitted with 3 days of abdominal distention, vomit, and the stoppage of the passage of gases and feces. She was admitted with poor clinical conditions with septic shock, acute respiratory distress syndrome, and signs of diffuse peritonitis. Abdominal radiography showed severe dilation of the colon with horseshoe signal suggesting a sigmoid volvulus, pneumoperitoneum and we could not we could not identify fetal heartbeats. With a diagnosis of complicate sigmoid volvulus she was underwent to the laparotomy where we found necrosis of all descending colon due to double twist volvulus of the sigmoid. We performed a colectomy with a confection of a proximal colostomy, and closing of the rectal stump. Due to an uncontrollable uterine bleeding during cesarean due, it was required a hysterectomy. The patient had an uneventful postoperative course thereafter and was discharged on a regular diet on the 15th postoperative day.
PMCID: PMC3335546  PMID: 22567527
15.  Tricholithobezoar Causing Gastric Perforation 
A bezoar is an intraluminal mass formed by the accumulation of undigested material in the gastrointestinal tract. Trichobezoar is a rare condition seen almost exclusively in young women with trichotillomania and trichotillophagia. When not recognized, the trichobezoar continues to grow, which increases the risk of severe complications such as gastric ulceration and even perforation. Formation of a gallstone within the trichobezoar (tricholithobezoar) is an event that has not yet been described. We report the case of a 22-year-old woman admitted to the emergency room with signals and symptoms of an epigastric mass and perforative acute abdomen. Radiological study revealed bilateral pneumoperitoneum. Personal history revealed depressive syndrome, trichotillomania and trichophagia. With a diagnosis of visceral perforation, an urgent exploratory laparotomy was performed. This confirmed the diagnosis of gastric perforation due to a large trichobezoar with the formation of a gastrolith that was removed by anterior gastrotomy. Biochemical study of the gastric stone revealed that it was composed of bile salts. There were no complications. The patient was discharged on the 5th postoperative day and was referred for psychiatric treatment.
PMCID: PMC3290022  PMID: 22379468
Bezoar; Trichobezoar; Hair balls; Trichotillomania; Lithiasis; Emotional disturbance; Therapy
16.  Glomus Tumor of the Stomach: A Rare Cause of Upper Gastrointestinal Bleeding 
Case Reports in Surgery  2011;2011:371082.
Introduction. Glomus tumors (GTs) are benign neoplasm originating from the glomus body, commonly described in subungual region. The involvement abdominal is rare. Our aim is to describe a case of glomus tumor of the stomach that presented upper gastrointestinal bleeding. A 34-year-old woman was admitted with upper gastrointestinal bleeding and underwent an upper endoscopy that showed bleeding arising from an ulcerated lesion, treated by sclerosis therapy. A new endoscopy confirmed a submucosal lesion in upper portion of the stomach. During the laparotomy, a tumor at the upper anterior wall of gastric body was found and resected by a vertical gastrectomy. The pathological exam revealed hyperplastic smooth muscle fibers of the muscularis propria of the stomach wall, surrounded by hyaline stroma. The immunohistochemistry panel was positive for smooth muscle actin and type IV collagen, with low rate of mitosis studied by Ki-67 which allowed the final diagnosis of a gastric glomus tumor. Discussion. The majority of intraperitoneal glomus tumors occur in the stomach, and it is phenotypically similar to those localized in peripheral sites. Gastric GT generally is a benign tumor although it can be malignant and have the potential to metastasize. Conclusion. Even though gastric glomus tumor is rarely described, it should be considered as a possible cause of a major upper gastrointestinal bleeding.
PMCID: PMC3350055  PMID: 22606576
19.  Jejunal Diverticular Perforation due to Enterolith 
Case Reports in Gastroenterology  2011;5(2):445-451.
Jejunal diverticulosis is a rare entity with variable clinical and anatomical presentations. Although there is no consensus on the management of asymptomatic jejunal diverticular disease, some complications are potentially life-threatening and require early surgical treatment. Small bowel perforation secondary to jejunal diverticulitis by enteroliths is rare. The aim of this study was to report a case of small intestinal perforation caused by a large jejunal enterolith. An 86-year-old woman was admitted with signs of diffuse peritonitis. After initial fluid recovery the patient underwent emergency laparotomy. The surgery showed that she had small bowel diverticular disease, mainly localized in the proximal jejunum. The peritonitis was due to intestinal perforation caused by an enterolith 12 cm in length, localized inside one of these diverticula. The intestinal segment containing the perforated diverticulum with the enterolith was removed and an end-to-end anastomosis was done to reconstruct the intestinal transit. The patient recovered well and was discharged from hospital on the 5th postoperative day. There were no signs of abdominal pain 1 year after the surgical procedure. Although jejunal diverticular disease with its complications, such as formation of enteroliths, is difficult to suspect in patients with peritonitis, it should be considered as a possible source of abdominal infection in the elderly patient when more common diagnoses have been excluded.
PMCID: PMC3180661  PMID: 21960947
Diverticulum; Intestines; Lithiasis; Intestinal perforation; Diverticulitis
20.  Ceramic microparticles and capsules via microfluidic processing of a preceramic polymer 
Journal of the Royal Society Interface  2010;7(Suppl 4):S461-S473.
We have developed a robust technique to fabricate monodispersed solid and porous ceramic particles and capsules from single and double emulsion drops composed of silsesquioxane preceramic polymer. A microcapillary microfluidic device was used to generate the monodispersed drops. In this device, two round capillaries are aligned facing each other inside a square capillary. Three fluids are needed to generate the double emulsions. The inner fluid, which flows through the input capillary, and the middle fluid, which flows through the void space between the square and inner fluid capillaries, form a coaxial co-flow in a direction that is opposite to the flow of the outer fluid. As the three fluids are forced through the exit capillary, the inner and middle fluids break into monodispersed double emulsion drops in a single-step process, at rates of up to 2000 drops s−1. Once the drops are generated, the silsesquioxane is cross-linked in solution and the cross-linked particles are dried and pyrolysed in an inert atmosphere to form oxycarbide glass particles. Particles with diameters ranging from 30 to 180 µm, shell thicknesses ranging from 10 to 50 µm and shell pore diameters ranging from 1 to 10 µm were easily prepared by changing fluid flow rates, device dimensions and fluid composition. The produced particles and capsules can be used in their polymeric state or pyrolysed to ceramic. This technique can be extended to other preceramic polymers and can be used to generate unique core–shell multimaterial particles.
PMCID: PMC2943890  PMID: 20484226
ceramic; microfluidic; capsule
21.  Ileal Intussusception Caused by Vanek's Tumor: A Case Report 
Case Reports in Gastroenterology  2011;5(1):110-116.
Inflammatory fibroid polyps (Vanek's tumor) are rare benign localized lesions originating in the submucosa of the gastrointestinal tract. Intussusceptions due to inflammatory fibroid polyps are uncommon; moreover, ileo-ileal intussusception with small bowel necrosis and perforation has rarely been reported. We report a 56-year-old woman who was admitted two days after complaints of nausea and vomiting. Abdominal examination revealed distension, signs of gastrointestinal perforation and clanging intestinal sounds. The patient underwent a emergency laparotomy which found a 17-cm invaginated mid-ileal segment with necrosis, perforation and fecal peritonitis. The ileal segment was resected and single-layer end-to-end anastomosis was performed. Histopathological analysis showed an ulcerative lesion with variable cellularity, formed by spindle cells with small number of mitosis and an abundant inflammatory infiltrate comprising mainly eosinophils. Immunohistochemistry confirmed the diagnosis of ileal Vanek's tumor. Although inflammatory fibroid polyps are seen very rarely in adults, they are among the probable diagnoses that should be considered in obstructive tumors of the small bowel causing intussusception with intestinal necrosis and perforation.
PMCID: PMC3078240  PMID: 21503167
Intestinal polyps; Polyps; Ileal neoplasm; Intussusception; Intestinal obstruction; Intestinal perforation; Immunohistochemistry
22.  Revisiting the Hetero-Fertilization Phenomenon in Maize 
PLoS ONE  2011;6(1):e16101.
Development of a seed DNA-based genotyping system for marker-assisted selection (MAS) has provided a novel opportunity for understanding aberrant reproductive phenomena such as hetero-fertilization (HF) by observing the mismatch of endosperm and leaf genotypes in monocot species. In contrast to conventional approaches using specific morphological markers, this approach can be used for any population derived from diverse parental genotypes. A large-scale experiment was implemented using seven F2 populations and four three-way cross populations, each with 534 to 1024 individuals. The frequency of HF within these populations ranged from 0.14% to 3.12%, with an average of 1.46%. The highest frequency of HF in both types of population was contributed by the pollen gametes. Using three-way crosses allowed, for the first time, detection of the HF contributed by maternal gametes, albeit at very low frequency (0.14%–0.65%). Four HF events identified from each of two F2 populations were tested and confirmed using 1032 single nucleotide polymorphic markers. This analysis indicated that only 50% of polymorphic markers can detect a known HF event, and thus the real HF frequency can be inferred by doubling the estimate obtained from using only one polymorphic marker. As expected, 99% of the HF events can be detected by using seven independent markers in combination. Although seed DNA-based analysis may wrongly predict plant genotypes due to the mismatch of endosperm and leaf DNA caused by HF, the relatively low HF frequencies revealed with diverse germplasm in this study indicates that the effect on the accuracy of MAS is limited. In addition, comparative endosperm and leaf DNA analysis of specific genetic stocks could be useful for revealing the relationships among various aberrant fertilization phenomena including haploidy and apomixis.
PMCID: PMC3023713  PMID: 21283522
23.  Surgical cryoablation as an option for small renal masses in patients who are not ideal partial nephrectomy candidates: intermediate-term outcomes 
There has been increasing interest in surveillance and ablative techniques for small renal masses (SRM), given the increasing number being diagnosed at smaller sizes. Of the currently available ablative techniques, radiofrequency ablation and cryoablation have been the popular ones. We describe our intermediate-term outcomes with using cryoablation for SRM in patients who were not ideal candidates for partial nephrectomy.
Materials and methods:
Nineteen patients treated with cryoablation were included. Patients with renal lesions <4 cm were considered for cryoablation, and all patients were treated between 2002 and 2007. Access was either laparoscopic (transperitoneal) or via open surgical techniques. From 2002 to 2004, the CryoCare System (Endocare, Inc., Irvine, CA) was used, with probe sizes ranging from 3 to 5 mm. Before 2004, the SeedNet system (Galil Medical, Arden Hills, MN) was used, with 17-gauge (1.47 mm) IceRod cryoneedles. Recurrence-free survival (RFS) and overall survival (OS) were calculated using Kaplan Meier methodology.
The mean age was 56.7 years. The mean tumour size was 2.6 cm (range 1.2–4.0 cm). There were no intraoperative or postoperative complications in the 19 patients. One patient has been lost to follow-up; mean follow up was 41.6 months (range 7–84 months) in the cohort. Recurrence, defined as either increase in size of lesion or enhancement on follow-up imaging, was seen in 4 patients. There was 1 non-cancer specific death, and 1 cancer specific death.
The 4-year RFS rate and OS rate were 83.6% and 94.1%, respectively, in patients with SRM who were unsuitable for partial nephrectomy.
PMCID: PMC2997831  PMID: 21191499
24.  Primary mucinous cystadenocarcinoma of the pelvic retroperitoneum in a male 
Primary mucinous cystadenocarcinoma of the retroperitoneum is an extremely rare malignancy with only 2 male patients reported in the literature. We describe an unusual case presenting as a pelvic mass in a male with previous pan-proctocolectomy and end ileostomy for Crohn’s disease and review the available literature.
PMCID: PMC3038378  PMID: 21749814
25.  A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients 
Nephrology Dialysis Transplantation  2010;26(5):1599-1607.
Background. Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in non-dialysis-dependent chronic kidney disease (ND-CKD) patients. Current intravenous iron agents cannot be administered in a single high dose because of adverse effects. Ferric carboxymaltose, a non-dextran parenteral iron preparation, can be rapidly administered in high doses.
Methods. This open-label trial randomized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m2, haemoglobin ≤ 11 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL, and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min (with up to two additional doses of 500 mg at 2-week intervals) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days.
Results. In the modified intent-to-treat population, the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4% with ferric carboxymaltose and 34.7% with oral iron (P < 0.001). At Day 42, mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL (P = 0.005), mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL (P < 0.001) and mean increase in transferrin saturation was 13.6 ± 11.9% vs 6.1 ± 8.1% (P < 0.001). Treatment-related adverse events were significantly fewer with ferric carboxymaltose than with oral iron (2.7% and 26.2%, respectively; P < 0.0001).
Conclusions. We conclude that 1000 mg ferric carboxymaltose can be rapidly administered, is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients.
PMCID: PMC3084440  PMID: 20929915
anaemia; CKD; ferritin; intravenous iron; transferrin saturation

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