Background & Aims
An inadequately cleansed colon can lead to missed lesions, repeat procedures, increased cost, and complications from colonoscopy. Because obesity, with its known link to colorectal neoplasia, might be associated with inadequate bowel cleansing, we investigated the impact of increased body mass index (BMI) on quality of bowel preparation at colonoscopy.
All colonos-copy procedures performed at a tertiary referral center during a 4-month period were evaluated. Bowel preparation was assigned a unique composite outcome score that took into account a subjective bowel preparation score, earlier recommendation for follow-up colonoscopy as a result of inadequate bowel preparation, and the endoscopist's confidence in adequate evaluation of the colon. Univariate and multivariate logistic regression analyses were performed to identify the role of BMI in predicting an inadequate bowel preparation.
During the study period, 1588 patients (59.1% female; mean age, 57.4 ± 0.34 years) fulfilled inclusion criteria. An abnormal BMI (>25) was associated with an inadequate composite outcome score (P = .002). In multivariate logistic regression analyses, both BMI >25 (P = .04) and >30 (P = .006) were retained as independent predictors of inadequate bowel preparation. Each unit increase in BMI increased the likelihood of an inadequate composite outcome score by 2.1%. Additional independent predictors of inadequate preparation exponentially increased the likelihood of an inadequate composite outcome score; 7 additional risk factors identified 97.5% of over-weight patients with an inadequate composite outcome score.
Obesity is an independent predictor of inadequate bowel preparation at colonoscopy. The presence of additional risk factors further increases the likelihood of a poorly cleansed colon.
The resolution of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) attests to the important role of the gastrointestinal tract in glucose homeostasis. Previous studies in RYGB-treated rats have shown that the Roux limb displays hyperplasia and hypertrophy. Here, we report that the Roux limb of RYGB-treated rats exhibits reprogramming of intestinal glucose metabolism to meet its increased bioenergetic demands; glucose transporter-1 is up-regulated, basolateral glucose uptake is enhanced, aerobic glycolysis is augmented, and glucose is directed toward metabolic pathways that support tissue growth. We show that reprogramming of intestinal glucose metabolism is triggered by the exposure of the Roux limb to undigested nutrients. We demonstrate by positron emission tomography–computed tomography scanning and biodistribution analysis using 2-deoxy-2-[18F]fluoro-D-glucose that reprogramming of intestinal glucose metabolism renders the intestine a major tissue for glucose disposal, contributing to the improvement in glycemic control after RYGB.
Endoscopist fatigue potentially impacts colonoscopy. Fatigue is difficult to quantitate, but polyp detection rates between non-fatigued and fatigued time periods could represent a surrogate marker. We assessed whether timing variables impacted polyp detection rates at a busy tertiary care endoscopy suite.
Consecutive patients undergoing colonoscopy were retrospectively identified. Indications, clinical demographics, pre-procedural, and procedural variables were extracted from chart review; colonoscopy findings were determined from the procedure reports. Three separate timing variables were assessed as surrogate markers for endoscopist fatigue: morning vs. afternoon procedures, start times throughout the day, and queue position, a unique variable that takes into account the number of procedures performed before the colonoscopy of interest. Univariate and multivariate analyses were performed to determine whether timing variables and other clinical, pre-procedural, and procedural variables predicted polyp detection.
During the 4-month study period, 1,083 outpatient colonoscopy procedures (57.5±0.5 years, 59.5% female) were identified, performed by 28 endoscopists (mean 38.7 procedures/endoscopist), with a mean polyp detection rate of 0.851/colonoscopy. At least, one adenoma was detected in 297 procedures (27.4%). A 12.4% reduction in mean detected polyps was detected between morning and afternoon procedures (0.90±0.06 vs. 0.76±0.06, P = 0.15). Using start time on a continuous scale, however, each elapsed hour in the day was associated with a 4.6% reduction in polyp detection (P = 0.005). When queue position was assessed, a 5.4% reduction in polyp detection was noted with each increase in queue position (P = 0.016). These results remained significant when controlled for each individual endoscopist.
Polyp detection rates decline as time passes during an endoscopist’s schedule, potentially from endoscopist fatigue. Queue position may be a novel surrogate measure for operator fatigue.
Cord Colitis Syndrome (CCS) is a recently described diarrheal illness of uncertain pathogenesis that affects recipients of umbilical cord blood transplant (CBT) and is associated with negative cultures. CCS exhibits a peculiar histopathological appearance, as it commonly manifests as granulomatous inflammation involving the upper and lower gastrointestinal tract, with features of chronicity in the colon. Importantly, the treatment for CCS differs from that of acute Graft-versus-Host Disease (GvHD), which is commonly in the clinical differential diagnosis: CCS responds to antibiotic treatment, while acute GvHD responds to immunosuppression. We describe here the case of a 36-year-old woman with a history of acute myeloid leukemia who developed refractory diarrhea following CBT. Endoscopic biopsies of the stomach and colon revealed granulomatous inflammation, consisting of scattered ill-defined aggregates of epithelioid histiocytes, with associated mild neutrophilic inflammation and mildly increased epithelial cell apoptosis. In the colon, the granulomatous inflammation was associated with surface epithelial injury (including surface erosions) and contained occasional multinucleated epithelioid giant cells. Paneth cell metaplasia was present in the distal colon, but crypt architecture was preserved and there was no basal lymphoplasmacytosis. Special stains and immunohistochemical stains for infectious organisms were negative. A diagnosis of CCS was made, and the patient promptly responded to treatment with ciprofloxacin and metronidazole. We present this case to raise awareness of this newly described entity among pathologists, in order to facilitate its timely diagnosis and treatment.
cord colitis syndrome; graft-versus-host disease; granulomatous gastritis; granulomatous colitis; umbilical cord blood transplant
Pharynx is a common site of malignancy in the head and neck region. This study presents a series of 94 cases of pharyngeal malignancy conducted at Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand in the Department of Otorhinolaryngology for a period of one year (2009–2010). Mean age at presentation was 56.8 years (age range 18–100 years). Male:Female ratio was 8.4:1.0. Maximum patients belonged to lower socio-economic status as per Kuppuswamy’s classification (2003). Majority of them were farmer (38.2%) by occupation and belonged to rural areas. 90.4% patients had history of tobacco smoking. Dysphagia was the commonest chief complaint. The most common subsite was oropharynx (51.0%) followed by hypopharynx (45.7%). Ulceroproliferative growth was the most common clinical finding. Histopathologically, squamous cell carcinoma (94.6%) was the commonest. CECT was the commonest and most useful radiological investigation done to see the extent of the disease.
Oropharynx malignancy; Pharynx malignancy; Nasopharynx; Hypopharynx malignancy
Coagulopathy in acute promyelocytic leukemia (APL) is a very complex disorder and is believed to result from interplay of various factors. Usually patients present with bleeding tendencies which can be life threatening. However, a few present with thromboses. Here, we report a young male with APL who presented with ischemic stroke in young.
Vascular anomalies are a heterogeneous group of congenital blood vessel disorders more typically referred to as birthmarks. Subcategorized into vascular tumors and malformations, each anomaly is characterized by specific morphology, pathophysiology, clinical behavior, and management approach. Hemangiomas are the most common vascular tumors. Lymphatic, capillary, venous, and arteriovenous malformations make up the majority of vascular malformations. Arteriovenous malformation of the head and neck is a rare vascular anomaly but when present is persistent and progressive in nature and can represent a lethal benign disease. Here we present a case report of a 25-year-old male patient with arteriovenous malformation involving the base of tongue.
Hematopoietic stem cell transplantation (HSCT) is a definite cure for many hematological diseases. With the increasing indications for HSCT and its relatively low cost in Indian subcontinent, an increasing number of patients are opting for this procedure. We retrospectively analyzed the cost of one hundred sixty two HSCTs done at our center in the last three years. The median cost of autologous transplant was USD, $ 12,500 (range $ 10,331–39,367) and the median cost of allogeneic transplant was $ 17,914 (range $ 10,832–44,701). The cost of HSCT is cheaper here compared to that in developed countries and success rates are nearly equivalent. The major factors contributing to the cost are related to the complications post-transplant mainly infections and graft versus host disease, which are also the reasons for the increased stay in the hospital.
Aminoglycoside (AMG)-induced renal toxicity is well-known and may manifest with non-oliguric renal failure or renal tubular dysfunction like Fanconi-like syndrome, Barter syndrome-like syndrome or distal renal tubular acidosis (RTA). These phenomena have been described with Gentamycin and Amikacin though rarely with Kanamycin. We present two cases of pulmonary tuberculosis that were treated with Kanamycin and during the course of treatment, developed severe recalcitrant hypocalcemia along with hypomagnesemia.
Hypocalcemia; hypomagnesemia; kanamycin; multidrug-resistant tuberculosis
Indoleamine 2,3 dioxygenase 1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn’s disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine.
Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. Montreal classification was used for disease phenotyping. Disease severity was categorized by physician’s global assessment. Serum tryptophan and kynurenine were measured by high pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks.
25 CD patients and 11 controls were enrolled. 8 CD patients had serum collected at two different time points and levels of disease activity. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened.
IDO1 expression in Crohn’s disease is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve a reasonable objective marker of gut mucosal immune activation and surrogate for Crohn’s Disease activity.
Indoleamine 2,3 dioxygenase; tryptophan; Crohn; Biomarker
Mucositis is a known complication following use of chemotherapy, but fatal mucositis is unusual and management of such cases may be challenging. Pathologically there is denudation of mucosa of gastrointestinal tract. Severe cases can develop ileus and even perforation of bowel wall. We report here a case of multiple myeloma who developed World Health Organization grade 4 gut mucositis following the use of high dose melphalan with the expulsion of “intestine-like” material.
Gastrointestinal mucositis; Chemotherapy
The lateral horn (LH) of the insect brain is thought to play several important roles in olfaction including maintaining the sparseness of responses to odors by means of feed-forward inhibition, and encoding preferences for innately meaningful odors. Yet, relatively little is known of the structure and function of LH neurons (LHNs) making it difficult to evaluate these ideas. Here we surveyed more than 250 LHNs in locusts using intracellular recordings to characterize their responses to sensory stimuli, dye-fills to characterize their morphologies, and immunostaining to characterize their neurotransmitters. We found a great diversity of LHNs, suggesting this area may play multiple roles. Yet, surprisingly, we found no evidence to support a role for these neurons in the feed-forward inhibition proposed to mediate olfactory response sparsening; instead, it appears that another mechanism, feed-back inhibition from the giant GABAergic neuron (GGN), serves this function. Further, all LHNs we observed responded to all odors we tested, making it unlikely these LHNs serve as labeled-lines mediating specific behavioral responses to specific odors. Our results rather point to three other possible roles of LHNs: extracting general stimulus features such as odor intensity; mediating bilateral integration of sensory information; and integrating multimodal sensory stimuli.
The National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) Enterprise Information System (DAIDS-ES) is a web-based system that supports NIAID in the scientific, strategic, and tactical management of its global clinical research programs for HIV/AIDS vaccines, prevention, and therapeutics. Different from most commercial clinical trials information systems, which are typically protocol-driven, the DAIDS-ES was built to exchange information with those types of systems and integrate it in ways that help scientific program directors lead the research effort and keep pace with the complex and ever-changing global HIV/AIDS pandemic. Whereas commercially available clinical trials support systems are not usually disease-focused, DAIDS-ES was specifically designed to capture and incorporate unique scientific, demographic, and logistical aspects of HIV/AIDS treatment, prevention, and vaccine research in order to provide a rich source of information to guide informed decision-making. Sharing data across its internal components and with external systems, using defined vocabularies, open standards and flexible interfaces, the DAIDS-ES enables NIAID, its global collaborators and stakeholders, access to timely, quality information about NIAID-supported clinical trials which is utilized to: (1) analyze the research portfolio, assess capacity, identify opportunities, and avoid redundancies; (2) help support study safety, quality, ethics, and regulatory compliance; (3) conduct evidence-based policy analysis and business process re-engineering for improved efficiency. This report summarizes how the DAIDS-ES was conceptualized, how it differs from typical clinical trial support systems, the rationale for key design choices, and examples of how it is being used to advance the efficiency and effectiveness of NIAID's HIV/AIDS clinical research programs.
Clinical trials management; medical informatics; enterprise architecture; web services; NIH, clinical research informatics
Insects can learn, allowing them great flexibility for locating seasonal food sources and avoiding wily predators. Because insects are relatively simple and accessible to manipulation, they provide good experimental preparations for exploring mechanisms underlying sensory coding and memory. Here we review how the intertwining of memory with computation enables the coding, decoding, and storage of sensory experience at various stages of the insect olfactory system. Individual parts of this system are capable of multiplexing memories at different timescales, and conversely, memory on a given timescale can be distributed across different parts of the circuit. Our sampling of the olfactory system emphasizes the diversity of memories, and the importance of understanding these memories in the context of computations performed by different parts of a sensory system.
To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN).
This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease.
Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks).
Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.
Acute retinal necrosis; Herpetic retinitis; Acyclovir; Valacyclovir
Most proteomics studies attempt to maximize the number of peptide identifications and subsequently infer proteins containing two or more peptides as reliable protein identifications. In this study, we evaluate the effect of this “two-peptide” rule on protein identifications, using multiple search tools and data sets. Contrary to the intuition, the “two-peptide” rule reduces the number of protein identifications in the target database more significantly than in the decoy database and results in increased false discovery rates, compared to the case when single-hit proteins are not discarded. We therefore recommend that the “two-peptide” rule should be abandoned, and instead, protein identifications should be subject to the estimation of error rates, as is the case with peptide identifications. We further extend the generating function approach (originally proposed for evaluating matches between a peptide and a single spectrum) to evaluating matches between a protein and an entire spectral data set.
two-peptide rule; false discovery rate; mass spectrometry; peptide identification; protein identification; decoy database; false positives
The target-decoy approach (TDA) has done the field of proteomics a great service by filling in the need to estimate the false discovery rates (FDR) of peptide identifications. While TDA is often viewed as a universal solution to the problem of FDR evaluation, we argue that the time has come to critically re-examine TDA and to acknowledge not only its merits but also its demerits. We demonstrate that some popular MS/MS search tools are not TDA-compliant and that it is easy to develop a non-TDA compliant tool that outperforms all TDA-compliant tools. Since the distinction between TDA-compliant and non-TDA compliant tools remains elusive, we are concerned about a possible proliferation of non-TDA-compliant tools in the future (developed with the best intentions). We are also concerned that estimation of the FDR by TDA awkwardly depends on a virtual coin toss and argue that it is important to take the coin toss factor out of our estimation of the FDR. Since computing FDR via TDA suffers from various restrictions, we argue that TDA is not needed when accurate p-values of individual Peptide-Spectrum Matches are available.
Computational proteomics; Target-decoy approach; False discovery rate; False positive rate; Database search; Decoy database; P-value
While trypsin remains the most commonly used protease in mass spectrometry, other proteases may be employed for increasing peptide-coverage or generating overlapping peptides. Knowledge of the accurate specificity rules of these proteases is helpful for database search tools to detect peptides, and becomes crucial when label-free mass spectrometry is used to discover in vivo proteolytic cleavages. Since in vivo cleavages are inferred by subtracting digestion-induced cleavages from all observed cleavages, it is important to ensure that the specificity rule used to identify digestion-induced cleavages are broad enough to capture even minor cleavages produced in digestion, to avoid erroneously identifying them as in vivo cleavages. In this study, we describe MS-Proteolysis, a software tool for identifying putative sites of in vivo proteolytic cleavage using label-free mass spectrometry. The tool is used in conjunction with digestion by trypsin and three other proteases, whose specificity rules are revised and extended before inferring proteolytic cleavages. Finally, we show that comparative analysis of multiple proteases can be used to detect putative in vivo proteolytic sites on a proteome-wide scale.
mass spectrometry; label-free; protease specificity; trypsin; V8 protease; CNBr; chymotrypsin; proteolysis
Diverse neuropeptides participate in cell–cell communication to coordinate neuronal and endocrine regulation of physiological processes in health and disease. Neuropeptides are short peptides ranging in length from ~3 to 40 amino acid residues that are involved in biological functions of pain, stress, obesity, hypertension, mental disorders, cancer, and numerous health conditions. The unique neuropeptide sequences define their specific biological actions. Significantly, this review article discusses how the neuropeptide field is at the crest of expanding knowledge gained from mass-spectrometry-based neuropeptidomic studies, combined with proteomic analyses for understanding the biosynthesis of neuropeptidomes. The ongoing expansion in neuropeptide diversity lies in the unbiased and global mass-spectrometry-based approaches for identification and quantitation of peptides. Current mass spectrometry technology allows definition of neuropeptide amino acid sequence structures, profiling of multiple neuropeptides in normal and disease conditions, and quantitative peptide measures in biomarker applications to monitor therapeutic drug efficacies. Complementary proteomic studies of neuropeptide secretory vesicles provide valuable insight into the protein processes utilized for neuropeptide production, storage, and secretion. Furthermore, ongoing research in developing new computational tools will facilitate advancements in mass-spectrometry-based identification of small peptides. Knowledge of the entire repertoire of neuropeptides that regulate physiological systems will provide novel insight into regulatory mechanisms in health, disease, and therapeutics.
bioinformatics; cell–cell communication; mass spectrometry; neuropeptides; neuropeptidomics; proteomics; secretory vesicle
Research on anger attacks has been mostly limited to depression, and only a few studies have focused on anger attacks in obsessive compulsive disorder.
Materials and Methods:
In a cross-sectional study all new obsessive compulsive disorder patients aged 20-60 years attending an outpatient clinic were assessed using the anger attack questionnaire, irritability, depression and anxiety scale (for the direction of the aggressive behavior) and quality of life (QOL).
The sample consisted of 42 consecutive subjects with obsessive compulsive disorder, out of which 21 (50%) had anger attacks. The obsessive compulsive disorder subjects with and without anger attacks did not show significant differences in terms of sociodemographic variables, duration of illness, treatment, and family history. However, subjects with anger attacks had significantly higher prevalence of panic attacks and comorbid depression. Significantly more subjects with anger attacks exhibited aggressive acts toward spouse, parents, children, and other relatives in the form of yelling and threatening to hurt, trying to hurt, and threatening to leave. However, the two groups did not differ significantly in terms of QOL, except for the psychological domain being worse in the subjects with anger attacks.
Anger attacks are present in half of the patients with obsessive compulsive disorder, and they correlate with the presence of comorbid depression.
Anger attacks; obsessive compulsive disorder; depression
Management of anterior skull base tumors is complex due to the anatomic detail of the region and the variety of tumors that occur in this area. Currently, the “gold standard” for surgery is the anterior craniofacial approach. Craniofacial resection represents a major advance in the surgical treatment of tumors of the paranasal sinuses involving anterior skull base. It allows wide exposure of the complex anatomical structures at the base of skull permitting monobloc tumor resection. This study presents a series of 18 patients with anterior skull base tumors, treated by a team of head-neck surgeons and neurosurgeons. The series included 15 malignant tumors of the nose and paranasal sinuses and 3 extensive benign lesions. All tumors were resected by a combined bi-frontal craniotomy and rhinotomy. The skull base was closed with a pediculated pericranial flap and a split-thickness free skin graft underneath. There were no postoperative problems of wound infection, cerebrospinal fluid-leakage or meningitis. Recurrent tumor growth or systemic metastasis occurred in 3 out of 15 patients with malignant tumors, 6 months to 2 years postoperatively. Craniofacial resection was thus found to give excellent results with low morbidity in malignant lesions and can also be adapted for benign tumors of anterior skull base.
Craniofacial approach; Anterior skull base tumor
Unicystic ameloblastoma refers to those cystic lesions that show clinical, radiographic or gross features of a jaw cyst but on histologic examination show a typical ameloblastomatous epithelium lining the cyst cavity, with or without luminal and/or mural tumor proliferation unicystic ameloblastoma is a less encountered variant of the ameloblastoma and believed to be less aggressive. As this tumor shows considerable similarities with dentigerous cysts, both clinically and radiographically the biologic behaviour of this tumor group was reviewed. Moreover, recurrence of unicystic ameloblastoma may be long delayed and a long-term post-operative follow up is essential for proper management of these patients. Here we are presenting a case of unicystic ameloblastoma in a 18 year old female patient.
Luminal proliferation; stellate reticulum; unicystic ameloblastoma
Managing hematological disorders in a tropical country presents several unique diagnostic and management problems. Apart from the disease process, we need to be aware of infections that can exacerbate or mimic serious hematological problems. We present here a series of five patients with pre-existing hematological diseases who were infected by dengue virus. These cases highlight the need to keep a strong suspicion of common endemic diseases in tropical countries before considering extensive workup for the basic hematological disease. There was no mortality and all patients recovered without any significant impact on their pre-existing hematological condition inspite of their low baseline blood counts. There was no excessive bleeding, prolonged stay in the hospital or relapse of underlying hematological disease in these patients and the only major concern was the increased anxiety among both the patient and treating physician regarding the relapse/progression of pre-existing hematological disease.