Correlation of radiographic and endoscopic evaluation of gastrojejunal anastomosis after Roux-en-Y gastric bypass.

BACKGROUND: Anastomotic stenosis presents as one of the most common late complications in the postoperative period after bariatric surgery. It is often diagnosed by upper gastrointestinal series (UGIS) and/or upper endoscopy (UE). The aim of this study was to determine whether a correlation exists between the Gastrografin UGIS and UE findings in the determination of gastrojejunal anastomotic strictures after Roux-en-Y gastric bypass (RYGB). METHODS: Between July 2001 and October 2003, all medical records of patients who underwent RYGB at our institution were retrospectively reviewed. The medical records of patients who underwent UE because of symptoms suggestive of gastric outlet obstruction and those of patients who were initially evaluated by Gastrografin UGIS before UE were evaluated further. RESULTS: Of 535 morbidly obese patients who underwent RYGB, 52 (9.7%) had UE and were included in this study. The mean number of UEs performed per patient was 2.67. Of these 52 patients, 30 underwent Gastrografin UGIS before UE. The mean diameter of the anastomosis on the first UE was 5.97 mm and on Gastrografin UGIS was 6.83 mm. A good correlation was found between the Gastrografin UGIS and UE findings using Pearson's correlation coefficient (0.44, P = .02) and single linear regression analysis using the endoscopic diameter as the outcome and radiographic findings as the predictor (beta = 0.27, P = .025, 95% confidence interval 0.30-0.49). CONCLUSION: In our study, the Gastrografin UGIS findings correlated positively with the endoscopic gastrojejunal anastomosis findings in patients with anastomotic stricture who had undergone RYGB.     

Genetic testing for hearing loss: different motivations for the same outcome

Autism is a complex genetic disorder. Chromosome 15 is of particular interest in this disorder, because of previous reports of individuals with autism with chromosomal abnormalities in the 15q11-q13 region. Transmission disequilibrium between polymorphisms in this region and autism has been also been reported in some, but not all studies. Recently, a novel maternally expressed gene, ATP10C, was characterized and mapped to the chromosome 15q11-q13 region, 200 kb distal to UBE3A. It encodes a putative aminophospholipid translocase likely to be involved in the asymmetric distribution of proteins in the cell membrane. Preferential maternal expression has been demonstrated in fibroblasts and brain. Because of its physical location and imprinting pattern, ATP10C was considered to be a candidate gene for chromosome 15-associated autism. In an effort to find the genes responsible for autism in this chromosomal region, 1.5 kb of the 5' flanking region, as well as the coding and splicing regions of ATP10C, were screened for sequence variants. Several polymorphic markers including five nonsynonymous SNPs were identified. To investigate transmission disequilibrium between ATP10C and autism, a family-based association study was conducted for 14 markers in 115 autism trios. No significant transmission disequilibrium was found, suggesting ATP10C is unlikely to contribute strongly to susceptibility to autism in these families. However, due to limited power to detect genes of modest effect, the possible functional role of the nonsynonymous SNPs and the functional implications of the SNPs identified from 5' flanking region and intron 2 splicing region may be evaluated in further studies.     

Immune-deficient SCID and NOD/SCID mice models as functional assays for studying normal and malignant human hematopoiesis

 Many events and requirements of the developmental program of human hematopoietic stem cells have not yet been discovered. A major impediment has been the lack of an appropriate experimental system. At present the conditions for maintaining human stem cells in vitro are not fully known. As a result within a short period the small stem cell pool is lost due to differentiation, making it difficult to examine the correlation between these cells and their function in vivo. Most of our knowledge of hematopoietic stem cells is from animal models in which purified stem cell canididates are assayed based on their functional ability to rescue lethally conditioned recipients. The permanent correction of many genetic disorders of the hematopoietic system requires efficient methods for introducing genes into stem cells in vitro. However, progress has been hindered by the absence of preclinical models that assay the repopulating capacity of primitive human cells. In addition, the development of therapy for malignant diseases also requires assays to identify the target leukemic stem cells based on their ability to initiate the disease. The recent development of methods to transplant or implant both normal and leukemic cells into immune-deficient mice provides the foundation for human stem cell assays. These models assay the repopulating capacity of primitive human cells and provide an important approach to identify and characterize human stem cells, both normal and leukemic. This review focuses on the development of functional assays for normal and leukemic human stem cells and on the new insights that these models are beginning to provide on the organization of the human stem cell hierarchy. Received: 27 January 1997 / Accepted: 3 April 1997     

The Effect of Presleep Focal Attention Load on Subsequent Sleep Patterns

The hypothesis that a load on focal attention prior to sleep results in subsequent changes in sleep patterns was investigated. Eight females and 2 males slept in the laboratory for 4 nights: 2 adaptation nights, 1 experimental night preceded by a focal attention load, and 1 control night preceded by relaxed activity. On the experimental night, time in bed, total sleep time, and stage REM sleep were significantly longer than on the control night. The results support the hypothesis and suggest that attention during REM sleep has a unique character.     

Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells

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The associations between reflective ability and communication skills among medical students

ObjectivesAssess associations between medical students’ reflective ability demonstrated in written narratives, and communication skills demonstrated later in simulated-patient breaking bad news interactions.MethodsWe analyzed 66 medical students’ reflective ability, using ‘REFLECT’ rubric and four newly developed parameters: Noticing Explanations provided to patients, Noticing Emotions, Remoteness/Connectedness in their writing, and mentioning Self-Emotions. ‘BAS’ and ‘SPIKES’ questionnaires measured students’ communication skills. Spearman and Chi-square tests examined correlations among all variables. Multiple regressions examined associations between reflective ability and demographic variables with communication skills.ResultsSignificant positive correlations between students’ reflective ability, measured by REFLECT and three of the new parameters, and global communication skill scores. Reflective ability of Noticing Explanations in writing was associated with ability to tailoring information to patients’ needs and address emotions.ConclusionsHigh reflective ability may improve communication skills. Specifically, ability to notice explanations to patients may enhance later capability to tailor information to patients and address emotions empathically.Practice implicationsEncourage educational interventions enhancing reflective ability; specifically observation and detailed writing about how explanations are given to patients and patients’ reactions to them. This process may help students develop competency to share and tailor difficult information sensitively—a critical skill when communicating bad news.     

Isolation and Chimerization of a Highly Neutralizing Antibody Conferring Passive Protection against Lethal Bacillus anthracis Infection

Several studies have demonstrated that the passive transfer of protective antigen (PA)-neutralizing antibodies can protect animals against Bacillus anthracis infection. The standard protocol for the isolation of PA-neutralizing monoclonal antibodies is based upon a primary selection of the highest PA-binders by ELISA, and usually yields only few candidates antibodies. We demonstrated that by applying a PA-neutralization functionality-based screen as the primary criterion for positive clones, it was possible to isolate more than 100 PA-neutralizing antibodies, some of which exhibited no measurable anti-PA titers in ELISA. Among the large panel of neutralizing antibodies identified, mAb 29 demonstrated the most potent activity, and was therefore chimerized. The variable region genes of the mAb 29 were fused to human constant region genes, to form the chimeric 29 antibody (cAb 29). Guinea pigs were fully protected against infection by 40LD₅₀ B. anthracis spores following two separate administrations with 10 mg/kg of cAb 29: the first administration was given before the challenge, and a second dose was administered on day 4 following exposure. Moreover, animals that survived the challenge and developed endogenous PA-neutralizing antibodies with neutralizing titers above 100 were fully protected against repeat challenges with 40LD₅₀ of B. anthracis spores. The data presented here emphasize the importance of toxin neutralization-based screens for the efficient isolation of protective antibodies that were probably overlooked in the standard screening protocol. The protective activity of the chimeric cAb 29 demonstrated in this study suggest that it may serve as an effective immunotherapeutic agent against anthrax.     

The use of the hydrodynamic HBV animal model to study HBV biology and anti-viral therapy.

A simple reproducible and versatile small animal model for hepatitis B virus (HBV) infection is still unavailable. We have generated a simple transient liver-targeted transgenic mouse. Hydrodynamics tail vein injection of a head-to-tail dimer of adw HBV genome (pHBVadwHTD) into immunocompetent mice generated HBsAg and HBeAg expression in both serum and hepatocytes, followed by seroconversion. The injection of pHBVadwHTD into SCID mice generated prolonged HBsAg and HBeAg antigenemia and HBV viremia. Our results demonstrate that hydrodynamic injection of naked DNA could support the generation of HBV particles. We used this model for the assessment of anti-viral agents. Administration of our human monoclonal antibodies, HBV-Ab17(XTL) and HBV-Ab19(XTL), as well as Lamivudine (3TC) treatment suppressed HBV viremia. The model presented herein supports long and stable expression of HBV and will enable determination of various biological questions related to HBV life cycle, mutants and could enhance the development of anti-viral reagents.     

Iron dysregulation in Alzheimer's disease: multimodal brain permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents

Considering the multi-etiological character of Alzheimer's disease (AD), the current pharmacological approaches using drugs oriented towards a single molecular target possess limited ability to modify the course of the disease and thus, offer a partial benefit to the patient. In line with this concept, novel strategies include the use of a cocktail of several drugs and/or the development of a single molecule, possessing two or more active neuroprotective-neurorescue moieties that simultaneously manipulate multiple targets involved in AD pathology. A consistent observation in AD is a dysregulation of metal ions (Fe²⁺, Cu²⁺ and Zn²⁺) homeostasis and consequential induction of oxidative stress, associated with beta-amyloid aggregation and neurite plaque formation. In particular, iron has been demonstrated to modulate the Alzheimer's amyloid precursor holo-protein expression by a pathway similar to that of ferritin L-and H-mRNA translation through iron-responsive elements in their 5′UTRs. This review will discuss two separate scenarios concerning multiple therapy targets in AD, sharing in common the implementation of iron chelation activity: (i) novel multimodal brain-permeable iron chelating drugs, possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities; (ii) natural plant polyphenols (flavonoids), such as green tea epigallocatechin gallate (EGCG) and curcumin, reported to have access to the brain and to possess multifunctional activities, such as metal chelation-radical scavenging, anti-inflammation and neuroprotection.