OBJECTIVE

Difficult or incomplete colonoscopes occasionally occur due to variable colonic anatomy and fixation. The aim of this study was to determine whether different types of colonoscopes used would affect the colonoscopic performance and sedation practice.

METHODS

Consecutive patients attending for health examination were randomized to examination with either the Olympus GIF-Q260 (OS) or Fujinon EC-450 (FS). The cecal intubation rate and time were evaluated. The dose for sedation was also compared.

RESULTS

Among 86 subjects, 44 were performed with the OS scope and 42 with the FS. Intubation time was quicker with the FS than OS (3.6±0.3 vs. 4.7±0.4min, p=0.024). The intubation rate was not statistically different between the OS and FS groups (p=ns). The total dose of sedation used was similar between OS and FS groups (p=ns). The intubation time correlated negatively with body weight (r=-0.28, p=0.01).

CONCLUSIONS

The FS colonoscope appears to provide additional advantage by improving the speed of cecal intubation without compromising the intubation rate or increasing sedation dose, although the two types of colonoscopes are equally efficient in colonoscopic performance.

OBJECTIVE

Megaloblastic anemia during infancy and early childhood often reflects a hereditary disorder of cobalamin's absorption, transport, or intracellular metabolism. There are 3 well defined autosomal recessive syndromes manifesting with megaloblastic anemia due to defects in cobalamin absorption or transport, namely congenital pernicious anemia, Imerslund-Grasbeck syndrome and Transcobalamin II deficiency. The genes responsible for the 3 disorders are gene intrinsic factor (GIF), MGA1 and TCN2, as well as the gene for Transcobalamin I, TCN1 are mapped or cloned, or both.

METHODS

We describe the clinical picture of 7 patients from 3 sibships, belong to one large inbred family who presented with megaloblastic anemia during infancy. The mode of inheritance follows an autosomal recessive pattern and the syndrome was completely reversed by parentral vitamin B12 therapy. The ascertainment of the family was carried out in 1998 in the Princess Rhama Children's Hospital, which is affiliated with Jordan University of Science and Technology, Jordan. We performed linkage analysis in this family for genes or regions involved in the above mentioned disorders.

RESULTS

The genes implicated in the etiology of the previously mentioned disorders were excluded from being responsible for the disorder in this family.

CONCLUSIONS

The exclusion of the involvement of GIF, MGA1, TCN1 and TCN2 in this family suggests that another gene and its product, involved in cobalamin absorption or transport, remains to be identified. A genome-wide search of the gene implicated in this family may give some insight on that gene, and its function.

Intrinsic factor deficiency (OMIM #261000, IFD) is a rare inherited disorder of vitamin B12 metabolism due to mutations in the gastric intrinsic factor (GIF) gene.We report three individuals from an Old Order Mennonite community who presented with B12 deficiency. Two cases are siblings born to consanguineous parents and the third case is not known to be closely related. The older male sib presented at 4 years with gastrointestinal symptoms, listlessness, and pallor. He had pancytopenia with megaloblastic anemia. Serum B12 was 61 (198-615 pmol/L). Methylmalonic aciduria was present. C3 was elevated on acylcarnitine profile. Homocysteine was high at 16.7 (5.0-12.0 umol/L). His asymptomatic female sibling was also found to have B12 deficiency. Genetic testing for methylmalonic aciduria (MMAA), transcobalamin deficiency (TCN2), and Imerslund-Gräsbeck syndrome (AMN) showed no mutation in both siblings. The third patient, a 34-year-old woman, had presented in infancy with a diagnosis of pernicious anemia. Mutation analysis of GIF revealed compound heterozygosity for a c.79+1G>A substitution and a c.973delG deletion in all three individuals. Oral or parenteral vitamin B12 has led to complete recovery of clinical parameters and vitamin B12 levels. Newborn screening samples on the siblings revealed normal methylcitrate, C3, and C3/C2 ratios thus indicating no disruption of propionic or methylmalonic acid metabolism.A high index of suspicion should be maintained if children present with megaloblastic anemia since GIF deficiency is a treatable disorder and newborn screening may not be able to detect this condition.

OBJECTIVE

Juvenile megaloblastic anemia is a rare and often hereditary disorder of cobalamin absorption, transport or intracellular metabolism. Several syndromes present with megaloblastic anemia such as congenital megaloblastic anemia due to intrinsic factor defect and juvenile megaloblastic anemia with proteinuria due to defects in the cubilin or the amnionless protein.

METHODS

We identified a large kindred with juvenile megaloblastic anemia. Four genes, GIF, CUBN, TCN1, and TCN2, was previously excluded from being responsible for the syndrome of this family who was discovered in Irbid, Jordan, during the year 1999. At that time, the amnionless (AMN) gene was not yet known to implicate in megaloblastic anemia. In this study, we screened the AMN for mutations in the Ohio State University, Iowa, United States of America. In addition, follow-up testing was carried out in the University of Iowa in 2004.

RESULTS

We identified a homozygous splice site mutation in the patients. This mutation was previously detected in families from Turkey and Tunisia. It is suspected to be a founder mutation of Middle Eastern origin.

CONCLUSIONS

Molecular testing for this specific mutation in cases of Middle Eastern origin is a valuable tool for presymptomatic diagnosis, carrier identification and perhaps prenatal diagnosis.

Only very rarely do multiple parapapillary choledochoduodenal fistulas occur concurrently with ampullary carcinoma. The following presents just such a case, which occurred in a 51 year-old Japanese female hospitalized for epigastralgia. Gastrointestinal fiberscopy (GIF) showed abnormal swelling of Vater's papilla. She was diagnosed as having ampullary carcinoma and choledochoduodenal fistulas, as determined by hypotonic duodenography (HDG), endoscopic retrograde cholangiopancreatography (ERCP) and from the histopathology of the ampullary mucosal biopsy. Pancreatoduodenectomy was performed. We postulated that the multiple fistulas were formed on the longitudinal fold of Vater's papilla by an ampullary carcinoma, and that the fistulas played a major role in bile drainage. As a result, jaundice was not seen throughout the entire clinical course. We report on the mechanism of fistula formation, with a review of the recent literature.

Guided image filter (GIF) is a well-known local filter for its edge-preserving property and low computational complexity. Unfortunately, the GIF may suffer from halo artifacts, because the local linear model used in the GIF cannot represent the image well near some edges. In this paper, a gradient domain GIF is proposed by incorporating an explicit first-order edge-aware constraint. The edge-aware constraint makes edges be preserved better. To illustrate the efficiency of the proposed filter, the proposed gradient domain GIF is applied for single-image detail enhancement, tone mapping of high dynamic range images and image saliency detection. Both theoretical analysis and experimental results prove that the proposed gradient domain GIF can produce better resultant images, especially near the edges, where halos appear in the original GIF.

There are no current recommendations regarding the minimum technical specification for realtime telemedicine consultation in accident and emergency (A and E) practice. We assessed the effect of image resolution, compression, colour depth and display modality on perceived image quality and telediagnosis. Test sets of digitized radiographs and clinical images were subjected to a series of standardized manipulations and the resulting output files were evaluated by an expert panel using image scoring and receiver operating characteristic (ROC) analysis. For telemedicine in A and E work, the minimum technical specification should be regarded as images containing at least 250,000 pixels, compressed at up to JPEG 50 (or GIF for colour images) and displayed on a high-resolution computer monitor. These specifications resulted in average file sizes of 17 kByte for digital images and 9 kByte for radiographs.

Spleen cells from hyperimmunized mice infected with Toxoplasma gondii were cultured in vitro with Toxoplasma specific antigen. The supernatant produced from the cells were termed lymphokines (LKs). The LKs were divided into 4 major fractions, namely: LKs-I, LKs-II, LKs-III and LKs-IV, according to the elution pattern on Sephadex G-100 gel columns. Partially purified LKs contained 2 MIF peaks, namely: MIF-I in LKs-II fraction and MIF-II in LKs-IV fraction. In this study, Toxoplasma growth inhibitory factor (Toxo-GIF), which inhibits the multiplication of Toxoplasma within non-immune macrophages in vitro, was separated by the same method as MIF separation, i.e. Sephadex G-100 gel filtration. Toxo-GIF activity was present in the LKs-II fraction in which MIF-I was also detected with a calculated molecular weight of 30,000 to 40,000. This murine LKs inhibited Toxoplasma multiplication only in murine macrophages but not in guinea pig macrophages or canine monocytes. Cytotoxic substances against macrophages were observed in the LKs-IV fraction, however, no Toxo-GIF was present in this fraction which in addition contained MIF-II with a calculated molecular weight of 3,000 to 5,000.

Seventy two endoscopies of the upper gastrointestinal tract and one hundred and fifteen colonoscopies were performed in children aged nine months to seventeen years. The experience gained with different types of endoscopes suggests that endoscopy of the upper gastrointestinal tract should be only performed with pediatric instruments. These are: GIF-P2(1) (max. outer diameter 9 mm) and TX-7(2) (max. outer diameter 10mm). For colonoscopy, the ideal pediatric instrument is not yet available. Sigmoidocoloscopes like the CFMB1 (length 1115 mm) and the F-91-S2 (length 650 mm) are suitable for older children.

Energy loss spectroscopic profiling is a way to acquire, in parallel, spectroscopic information across a linear feature of interest, using a Gatan imaging filter (GIF) fitted to a transmission electron microscope (TEM). This technique is capable of translating the high spatial resolution of a bright field image into a sampling of the spectral information with similar resolution. Here we evaluate the contributions of chromatic aberration and the various acquisition parameters to the spatial sampling resolution of the spectral information, and show that this can reach 0.5 nm, in a system not ordinarily capable of forming electron probes smaller than 2 nm. We use this high spatial sampling resolution to study the plasmon energy variation across amorphous carbon superlattices, in order to extract information about their structure and electronic properties. By modelling the interaction of the relativistic incident electrons with a dielectric layer sandwiched between outer layers, we show that, due to the screening of the interfaces and at increased collection angles, the plasmon energy in the sandwiched layer can still be identified for layer thicknesses down to 5 A. This allows us to measure the change in the well bandgap as a function of well width and to interpret it in terms of the changes in the sp2 -fractions due to the deposition method, as measured from the carbon K-edges, and in terms of quantum confinement of the well wavefunction by the adjacent barriers.

In the last two decades conventional linear methods for biosignal analysis have been substantially extended by non-stationary, non-linear, and complexity approaches. So far, complexity is usually assessed with regard to one single time scale, disregarding complex physiology organised on different time scales. This shortcoming was overcome and medically evaluated by information flow functions developed in our research group in collaboration with several theoretical, experimental, and clinical partners. In the present work, the information flow is introduced and typical information flow characteristics are demonstrated. The prognostic value of autonomic information flow (AIF), which reflects communication in the cardiovascular system, was shown in patients with multiple organ dysfunction syndrome and in patients with heart failure. Gait information flow (GIF), which reflects communication in the motor control system during walking, was introduced to discriminate between controls and elderly patients suffering from low back pain. The applications presented for the theoretically based approach of information flow confirm its value for the identification of complex physiological systems. The medical relevance has to be confirmed by comprehensive clinical studies. These information flow measures substantially extend the established linear and complexity measures in biosignal analysis.

The rapid growth of social media over the last decade soon convinced businesses including medical practices and academic medical centers to enter the social media fray-for profit, education, and expanding access. Launched in 2010, Pinterest (San Francisco, CA, USA) differed from many of the established social media platforms by presenting collection and curation features based on the sharing of images rather than text. Thus, Pinterest allows users to categorize website links using photos, GIFs, and videos, and catalog them for future consideration, saved on a virtual folder or "pinboard." Facebook, Twitter, and LinkedIn are text-heavy social media platforms that do not allow for significant curating activities. Instagram, the other of the two primary photo-oriented social media giants, was launched the same year as Pinterest. Owned by Facebook, Instagram caters to a more personal experience and mostly relies on mobile technology. Because Pinterest users are mainly focused on finding and collecting other users' content, Pinterest is thought to generate website traffic and is more conducive to use on larger screens. It further distinguishes itself by encouraging appreciation/learning over self-promotion and its range of categories exceeds that of other such sites. Some of the more visually oriented medical specialties (i.e., dermatology, plastic surgery, and radiology) have begun to consider what role, if any, the popular site Pinterest, with more than 250 million monthly users, might play in disseminating healthy messages, reaching patients, and contributing to medical education. We investigated how Pinterest could work for our radiology education mission and then decided to establish a presence on the site to ascertain if creating our own board would have any practical benefits.

We previously reported on an altered immune-endocrine feedback loop via the hypothalamo-pituitary-adrenal (HPA) axis in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. These animals are deficient in plasma corticosterone increase after antigenic challenge or application of cytokine-containing conditioned medium of mitogen-stimulated spleen cells (CM). To investigate whether the impaired ability to respond to cytokines with glucocorticoid-increasing factor (GIF) activity, e.g. interleukin 1 (IL 1), is restricted to OS chickens as a model for an organ-specific autoimmune disease, we extended our experiments to another autoimmune-prone animal strain, the chickens of the University of California at Davis line 200 (UCD-200). These animals develop an inherited inflammatory fibrotic disease that closely resembles human progressive systemic sclerosis (scleroderma). Application of GIF-containing CM to UCD-200 chickens leads to a transient increase in glucocorticoid serum levels within 1-2 hours comparable to that of controls. But, while corticosterone levels in the latter returned to normal baseline levels after 4 hours, they were still elevated in autoimmune chickens. Although the peak of the glucocorticoid hormone serum concentrations was equal to that of controls, UCD-200 had to secrete twice as much adrenocorticotropic hormone to achieve this corticosterone serum level due to an apparent hyporesponsiveness of the adrenal gland to this secretagogue. The altered cytokine-induced glucocorticoid secretion is found in early as well as in chronic, sclerotic stages of the disease. Cellular alterations in the peripheral blood of UCD-200 chickens during the prolonged elevated corticosterone section, i.e. between 2-4 hours after CM application, are characterized by a significant decrease in the percentage of CD4+ and CD8+ cells. Furthermore, a significant increase in B cells up to 24 hours with a maximum after 1 hour was found. The proliferative response to the mitogen concanavalin A of peripheral mononuclear cells was inversely correlated to the serum corticosterone level, showing a permanent decrease of 80-90% after 1-4 hours in autoimmune animals. This functional alteration in UCD-200 was accompanied by an 80% decrease in serum interleukin 2 (sIL 2) activity 4 hours after CM application. Twenty-four hours later an eight-fold increase in sIL 2 rebound activity was found, indicating that the inhibitory effect of corticosterone in UCD-200 chickens is not long-lasting.

A factor which is responsible for the growth inhibitory properties of certain mouse sera and related to NK-activity, has been studied. The factor was isolated from hybrid B6D2F1 (C57Bl/6 x DBA/2) serum, which is histo-compatible with the mouse tumour (B16 melanoma) used and has high NK-activity. Growth inhibitory activity was measured in an in vitro assay. It was independent of complement activation. The responsive factor was isolated and characterized by ion exchange chromatography. Concanavalin A affinity chromatography, gel filtration and iso-electric focusing. It appears to be a protein and had been labelled growth-inhibitory factor (GIF). It has a molecular weight of 230 000-260 000 daltons and an iso-electric point in the pH range 4.6-5.0. It was not retained on Concanavalin A columns.

We examined the protective effect of growth inhibitory factor (GIF) against zinc-induced neuronal death in rat hippocampal neurons. In an in vitro cell culture system, 300 microM Zn(2+) readily induced death of hippocampal neuronal cells, which was characterized by massive necrosis and a minor degree of apoptosis. Neither the addition of recombinant GIF nor Rab3A alone could rescue these cells from death. However, the combination of GIF with Rab3A could significantly enhance the survival of the hippocampal neurons. This result was supported by both Annexin -V FITC/propidium dual staining and chromosomal DNA analysis. These findings suggest that GIF may inhibit Zn(2+)-induced neuronal death via its interaction with Rab3A.

Familial recurrence of anorectal malformations (ARMs) has been reported in single institution case series and in two population-based studies. Here, we investigate the familial aggregation of ARMs using well-established, unbiased methods in a population genealogy of Utah. Study subjects included 255 ARM cases identified from among the two largest healthcare providers in Utah with linked genealogy data using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. The genealogical index of familiality (GIF) statistic, which compares the average pair-wise relatedness of cases to sets of matched controls, was used to test excess familial clustering. We also estimated relative risks (RRs) for ARM and associated phenotypes in relatives of cases adjusting for age-, sex-, and birthplace. Significant excess familial clustering was observed for all ARM subjects (GIF p < 1e-3). Significant RR estimates for ARM (RR = 15.6, p = 3.3e-6), and for almost all co-morbid birth defects previously associated with ARM, were observed among first-degree relatives of ARM case subjects. This genealogically-based population survey of familial aggregation of ARMs confirms the presence of a heritable component to ARMs and provides unbiased risk estimates to relatives of cases, which may have clinical utility.

In its third year of existence, the French Phage Network (Phages.fr) is pursuing its expansion. With more than 25 groups, mostly based in France, working on the various aspects of phage research, the network has increased its visibility, interactivity, and activity. The third meeting of the Phages.fr network, held on November 2017 at the Gif-sur-Yvette Centre National de la Recherche Scientifique (CNRS) campus, was a great opportunity for many young scientists to present their work and interact with more senior scientists, amongst which several were invited from abroad. Here we provide a summary of the work presented at this occasion during the oral presentations and poster sessions.

Otolithic receptors are stimulated by gravitoinertial force (GIF) acting on the otoconia resulting in deflections of the hair bundles of otolithic receptor hair cells. The GIF is the sum of gravitational force and the inertial force due to linear acceleration. The usual clinical and experimental tests of otolith function have used GIFs (roll tilts re gravity or linear accelerations) as test stimuli. However, the opposite polarization of receptors across each otolithic macula is puzzling since a GIF directed across the otolith macula will excite receptors on one side of the line of polarity reversal (LPR at the striola) and simultaneously act to silence receptors on the opposite side of the LPR. It would seem the two neural signals from the one otolith macula should cancel. In fact, Uchino showed that instead of canceling, the simultaneous stimulation of the oppositely polarized hair cells enhances the otolithic response to GIF-both in the saccular macula and the utricular macula. For the utricular system there is also commissural inhibitory interaction between the utricular maculae in each ear. The results are that the one GIF stimulus will cause direct excitation of utricular receptors in the activated sector in one ear as well as indirect excitation resulting from the disfacilitation of utricular receptors in the corresponding sector on the opposite labyrinth. There are effectively two complementary parallel otolithic afferent systems-the sustained system concerned with signaling low frequency GIF stimuli such as roll head tilts and the transient system which is activated by sound and vibration. Clinical tests of the sustained otolith system-such as ocular counterrolling to roll-tilt or tests using linear translation-do not show unilateral otolithic loss reliably, whereas tests of transient otolith function [vestibular evoked myogenic potentials (VEMPs) to brief sound and vibration stimuli] do show unilateral otolithic loss. The opposing sectors of the maculae also explain the results of galvanic vestibular stimulation (GVS) where bilateral mastoid galvanic stimulation causes ocular torsion position similar to the otolithic response to GIF. However, GVS stimulates canal afferents as well as otolithic afferents so the eye movement response is complex.

Keywords: otolith; saccular; utricular; vemp; vestibular.

Small bowel biopsy is a difficult procedure in infants and children, and the authors describe a new technique. The Quinton multipurpose suction biopsy instrument is incorporated into an Olympus GIF-P2 fiberoptic endoscope to allow positioning of the biopsy capsule under direct visual control. Fourteen children, 2 months to 4 years of age, have been biopsied, and tissue was successfully obtained in 20 of 21 procedures. Nine of 21 endoscopic examinations of duodenal mucosa were abnormal and gave additional diagnostic information.

Glycosylation-inhibiting factor (GIF) is a 13-kDa cytokine secreted from T cells. Administration of bioactive recombinant GIF inhibits IgG1 and IgE Ab responses in vivo. Treatment of B cells with the cytokine reduces the secretion of IgG1 and IgE induced by LPS and IL-4. To examine the effect on cognate T-B interaction, GIF was added to low-density B cells from MD4 transgenic (Tg) mice, which express B cell receptor specific for hen egg lysozyme (HEL). The B cells were subsequently pulsed with HEL-OVA conjugate and cultured with OVA-specific naive CD4 T cells from DO11.10 Tg mice. Treatment of Ag-presenting B cells with GIF reduced expansion and IL-2 secretion of naive T cells and rendered them hyporesponsive to antigenic restimulation, resulting in 50--95% reduction of IL-4 and IFN-gamma secretion upon restimulation with Ag. GIF dramatically inhibited Th effector generation when it was added to B cells before pulsing with HEL-OVA, whereas it showed little to no effect when added after B cells were pulsed with Ag. GIF was more effective when B cells from MD4 Tg mice were pulsed with HEL-OVA than when they were pulsed with OVA. This cytokine did not affect Th effector generation when B cells or irradiated splenocytes pulsed with OVA(323--339) peptide stimulated naive DO11.10 T cells. Confocal microscopy revealed that GIF inhibited internalization of HEL by B cells from MD4 Tg mice. Therefore, the cytokine may regulate early steps of Ag presentation involving B cell receptors to diminish Th effector generation from naive CD4 T cells.

This study was to compare the suitability and precision of xerographic and computer-assisted methods for bite mark investigations. Eleven subjects were asked to bite on their forearm and the bite marks were photographically recorded. Alginate impressions of the subjects' dentition were taken and their casts were made using dental stone. The overlays generated by xerographic method were obtained by photocopying the subjects' casts and the incisal edge outlines were then transferred on a transparent sheet. The bite mark images were imported into Adobe Photoshop® software and printed to life-size. The bite mark analyses using xerographically generated overlays were done by comparing an overlay to the corresponding printed bite mark images manually. In computer-assisted method, the subjects' casts were scanned into Adobe Photoshop®. The bite mark analyses using computer-assisted overlay generation were done by matching an overlay and the corresponding bite mark images digitally using Adobe Photoshop®. Another comparison method was superimposing the cast images with corresponding bite mark images employing the Adobe Photoshop® CS6 and GIF-Animator©. A score with a range of 0-3 was given during analysis to each precision-determining criterion and the score was increased with better matching. The Kruskal Wallis H test showed significant difference between the three sets of data (H=18.761, p<0.05). In conclusion, bite mark analysis using the computer-assisted animated-superimposition method was the most accurate, followed by the computer-assisted overlay generation and lastly the xerographic method. The superior precision contributed by digital method is discernible despite the human skin being a poor recording medium of bite marks.

In order to capture and identify key molecules that regulate the release of Ca(2+) from the sarcoplasmic reticulum (SR) of skeletal muscle, we designed specific photoaffinity probes based on the structural modification of dantrolene. Thus, GIF-0082 and GIF-0276 possessing azido- and trifluoromethyldiazirinyl-benzyl groups, respectively, at the hydantoin moiety were found to have a highly selective inhibitory effect on physiological Ca(2+) release (PCR) without affecting Ca(2+)-induced Ca(2+) release (CICR). Successful realization of the sharp discrimination between PCR and CICR has led to the creation of [(125)I]GIF-0082 and [(125)I]GIF-0276, which were synthesized by substituting a stannyl group with (125)I in the corresponding phenylstannane precursors.

Glyoxylic acid-induced monoamine fluorescence (GIF) was used to map the distribution of catecholamine-containing cell bodies and terminals in the rat nucleus tractus solitarius (NTS) and dorsal medulla. In addition, the relative vascularity of the NTS was quantified by examination of tissue perfused with Pontamine sky blue. The GIF-reactive cell bodies within the NTS complex were caudal to the rostral pole of the area postrema and are therefore considered to be the A2 cell body group as defined by Dahlström and Fuxe. The A2 cell body group was composed of 900 (890 +/- 43, n = 3) small to medium sized neurons (15-25 micron diameter) located on the dorsal and lateral edges of the dorsal motor nucleus of the vagus. GIF terminal density was found to be most dense in the medial portion of the NTS as compared to the lateral or midline portions of the NTS, dorsal motor nucleus of the vagus, or hypoglossal nucleus. Quantitative blood vessel analysis revealed that the NTS is significantly less vascularized than the surrounding nucleus gracilius, central gray, or dorsal motor nucleus of the vagus. A full serial section analysis of NTS, stained either for GIF cell bodies, terminals or blood vessels, has been obtained; this detailed presentation of catecholamine-containing profiles and blood vessels in the dorsal medulla may facilitate future studies aimed at examining central control of autonomic function.