Takayasu arteritis developing during treatment of ulcerative colitis with infliximab

A 22-year-old female with ulcerative colitis that was successfully treated with infliximab (IFX), and remained stable following tapered discontinuation of prednisolone, developed anterior neck pain and elevation of C-reactive protein following her fourth administration of IFX. She was diagnosed with Takayasu arteritis (TA) based on neck ultrasound and computed tomography angiography. This is the first report describing the development of TA during treatment of UC with IFX.     

Population-based analysis of practices and costs of surveillance for colonic dysplasia in patients with primary sclerosing cholangitis and colitis

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and colitis are at risk of developing dysplasia and colorectal cancer (CRC). Consequently, annual surveillance colonoscopy with random biopsies is recommended. The aims of the present study were (1) to determine the incidence of dysplasia or CRC, (2) to assess surveillance practices, and (3) to assess the costs associated with surveillance of PSC patients. METHODS: A population-based study was conducted between 2000 and 2004 to identify all patients with a diagnosis of PSC using regional databases. Colonic histopathology reports of PSC patients with colitis were reviewed to determine the frequency of surveillance colonoscopies performed between 2000 and 2005, the number of biopsies retrieved, and the presence of CRC or dysplasia. The cost of annual surveillance colonoscopy with 33 random biopsies to detect 1 additional case of dysplasia was calculated from a local costs database. RESULTS: Forty-five PSC patients with ulcerative colitis or Crohn's disease were identified. Five patients (11.1%) were diagnosed with low-grade dysplasia (n = 2), dysplasia-associated lesion or mass (n = 2), or CRC (n = 1) during the 5-year follow-up period for an incidence rate of 3.1 events per 100 person-years (95% confidence interval: 1.0-7.2/100 person-years). Two of these lesions were detected through surveillance and 3 because of symptomatic presentation. Only 36% (56) of the expected number of surveillance colonoscopies were performed. The median number of biopsies collected was 27 (IQR: 19-33). The cost of surveillance to detect 1 additional case of dysplasia was USD 26,495. CONCLUSION: Despite a high rate of colorectal dysplasia or CRC among PSC patients, surveillance was suboptimal.     

EUS-guided angiography: a novel approach to diagnostic and therapeutic interventions in the vascular system

BACKGROUND: Indications for diagnostic and therapeutic procedures under EUS guidance continue to expand. OBJECTIVE: To assess the feasibility and safety of EUS-guided angiography in a live porcine model. SETTING: Five acute experiments under general anesthesia. DESIGN AND INTERVENTIONS: A linear echoendoscope was advanced into the stomach. Thoracic and abdominal aorta, celiac axis, superior mesenteric and splenic artery, splenic, portal, and hepatic veins were injected with contrast by using FNA needles under fluoroscopy. The animals were then killed for postmortem examination. MAIN OUTCOME MEASUREMENTS: Ability to achieve angiography without complications. RESULTS: All vessels were identified and punctured without technical difficulties. Injections of the large-caliber vessels resulted in a blush of contrast, whereas selective injection of the smaller vessels (splenic artery, hepatic veins) demonstrated clear vascular opacification. Injection of contrast was technically easiest with the 19-gauge FNA needle and most difficult with the 25-gauge needle. There were no changes in vital signs and hemodynamic parameters during vascular injection of any vessel. At necropsy, the 25-gauge FNA needle did not cause any visible vascular injury or bleeding. The 22-gauge needle left a visible puncture mark without active bleeding. In 1 of 5 pigs, the 19-gauge needle caused a localized vascular hematoma around large-caliber vessels and 150 mL of intra-abdominal blood. LIMITATION: Technical challenges remain to achieve an adequate flow rate of contrast for prolonged visualization of large vessels. CONCLUSION: EUS-guided angiography is technically easy and safe and has potential for a wide array of diagnostic and therapeutic vascular interventions.     

Notable intrafamilial phenotypic variability in a kindred with familial adenomatous polyposis and an APC mutation in exon 9

BACKGROUND: The phenotypic spectrum of familial adenomatous polyposis (FAP) varies from the classic appearance of hundreds of adenomatous colonic polyps in the young adult and early onset colorectal cancer, to the occurrence of sparse adenomas in the older adult, "attenuated" FAP, due to mutations at the 5' or 3' ends of the APC gene. AIMS: To investigate marked intrafamilial phenotypic variation occurring in a family with an APC gene mutation in exon 9. PATIENTS: An extended kindred of 22 people of whom 16 had colorectal neoplasia and/or were APC mutation carriers. RESULTS: Phenotypic manifestation varied from classic FAP to a complete lack of clinical or endoscopic, or bioptic disease in five people in three different generations. This occurred in four of them over two generations, in spite of having a confirmed 11 bp insertion causing a frame shift and stop codon (363) in exon 9 of the APC gene. CONCLUSIONS: At present, it is assumed that in this family there is alternative splicing of the APC gene, and/or unidentified modifying genetic factors. The family illustrates the importance of genetic testing in evaluating carrier status and not just clinical examination. This clinical observation also high- lights the dilemma in recognising the possible contribution of low penetrance germline APC mutations to what has been considered "sporadic" colorectal neoplasia.     

Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using matched and simulated controls: 5-year survival

Background/Aims: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for“prioritisation”, favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis.Methods: We compared the survival of 169 transplantedpatients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients.Results: The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58–74%) vs 52% (44–60; p=0.03) in the matched group and 54% (51–57; p=0.01) in the simulated controls. Transplantation was associated with survival (relative RISK=1.51; p=0.02), independently of risk score (risk=2.07; p<0.001), indication, period of inclusion, centre experience, and alcohol abstinence. Patients with severe disease (Pugh C11–15) benefited most in terms of 5-year survival: 58% (44–72) vs 31% (17–45; p=0.008) in the matched and 35% (30–40; p<0.001) in the simulated control groups. For patients at lower risk there was no significant difference.Conclusions: Liver transplantation increases the 5-year survival of patients with severe alcoholic cirrhosis. In patients at lower risk, efficacy of transplantation should be confirmed by longer follow-up or by randomised trial.     

Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding

BACKGROUND: Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring. METHODS: We undertook a pooled analysis of 7329 patients with nonvalvular atrial fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target international normalized ratio, 2.0-3.0). We determined annual risk of bleeding (any, major), case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment. RESULTS: Annual incidence of any bleeding was 31.75% with ximelagatran and 38.82% with warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0-23.1; P<.001). Annual incidence of major bleeding was 2.01% with ximelagatran and 2.68% with warfarin (relative risk reduction, 25.1%; 95% CI, 3.2-42.1; P = .03). Case-fatality rate of bleeding was comparable in ximelagatran- and warfarin-treated patients (8.16% vs 8.09%; P = .98). Cumulative incidence of major bleeding was higher with warfarin than ximelagatran after 24 months of treatment (4.7% vs 3.7%; P = .04). Anatomic sites of bleeding were comparable with both treatments. Risk factors for bleeding with ximelagatran were as follows (hazard ratios and 95% CIs in parentheses): diabetes mellitus (1.81; 1.19-2.77; P = .006), previous stroke or transient ischemic attack (1.78; 1.16-2.73; P = .008), age 75 years or greater (1.70; 1.33-2.18; P<.001), and aspirin use (1.68; 1.08-2.59; P = .02). Risk factors for bleeding in warfarin-treated patients were previous liver disease (4.88; 1.55-15.39; P = .007); aspirin use (2.41; 1.69-3.43; P<.001); and age 75 years or greater (1.26; 1.03-1.52; P = .02). CONCLUSIONS: Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation. Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.     

Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence

Mutations in ABCA4, which encodes a photoreceptor specific ATP-binding cassette transporter (ABCR), cause autosomal recessive forms of human blindness due to retinal degeneration (RD) including Stargardt disease. The exact disease sequence leading to photoreceptor and vision loss in ABCA4-RD is not known. Extrapolation from murine and in vitro studies predicts that two of the earliest pathophysiological features resulting from disturbed ABCR function in man would be slowed kinetics of the retinoid cycle and accelerated deposition of lipofuscin in the retinal pigment epithelium (RPE). To determine the human pathogenetic sequence, we studied surrogate measures of retinoid cycle kinetics, lipofuscin accumulation, and rod and cone photoreceptor and RPE loss in ABCA4-RD patients with a wide spectrum of disease severities. There were different extents of photoreceptor/RPE loss and lipofuscin accumulation in different regions of the retina. Slowing of retinoid cycle kinetics was not present in all patients; when present, it was not homogeneous across the retina; and the extent of slowing correlated well with the degree of degeneration. The orderly relationship between these phenotypic features permitted the development of a model of disease sequence in ABCA4-RD. The model predicted lipofuscin accumulation as a key and early component of the disease expression in man, as in mice. In man, however, abnormal slowing of the rod and cone retinoid cycle occurs at later stages of the disease sequence. Knowledge of the human ABCA4 disease sequence will be critical for defining rates of progression, selecting appropriate patients and retinal locations for future therapy, and choosing appropriate treatment outcomes.     

PCR analysis of egyptian respiratory adenovirus isolates, including identification of species, serotypes, and coinfections

Eighty-eight adenovirus (Ad) isolates and associated clinical data were collected from walk-in patients with influenza-like illness in Egypt during routine influenza surveillance from 1999 through 2002. Respiratory Ad distributions are geographically variable, and serotype prevalence has not been previously characterized in this region. Serotype identity is clinically relevant because it predicts vaccine efficacy and correlates strongly with both clinical presentation and epidemiological pattern. Species and serotype identities were determined using several well-validated multiplex PCR protocols culled from the literature and supplemented with a few novel primer sets designed to identify rare types. The isolates included common species B1 serotypes (Ad3 and Ad7), common species C serotypes (Ad1, Ad2, and Ad5), the less common species B2 serotype Ad11, and three isolates of the rare species B1 serotype Ad16. Two isolates that appear to be variant Ad16 were also identified. Fifteen coinfections of multiple adenoviral types, primarily AdB/AdC and Ad3/Ad7 dual infections, were detected. The majority of these were verified using redundant PCR tests targeted at multiple genes. PCR is able to resolve coinfections, in contrast to traditional serum neutralization tests. PCR is also comparatively rapid and requires very little equipment. Application of the method allowed an inclusive determination of the serotypes found in the Egyptian respiratory sample set and demonstrated that coinfections are common and may play a previously unrecognized role in adenovirus pathogenesis, evolution, and epidemiology. In particular, coinfections may influence adenoviral evolution, as interserotypic recombination has been identified as a source of emerging strains.     

Number magnitude potentiates action judgements

Motor actions can be simulated and generated through the perception of objects and their characteristics. Such functional characteristics of objects with given action capabilities are called affordances. Here we report an interaction between the perception of affordances and the processing of numerical magnitude, and we show that the numerical information calibrates the judgement of action even when no actual action is required. In Experiment 1, participants had to judge whether they would be able to grasp a rod lengthways between their thumb and index finger. The presentation of the rod was preceded by a number or a non-numerical symbol. When a small number preceded the rod, participants overestimated their grasp; conversely, when a large number preceded the rods, they underestimated their grasp. In Experiment 2, participants were requested to judge if two successive rods had the same length, a judgement that did not involve any grasping. The numerical primes had no effect on this judgement, showing that the magnitude/affordance interaction was not due to a simple perceptual effect. Finally, Experiment 3 showed that the interaction was not present with a non-numerical ordered sequence, thereby eliminating sequence order as a potentially confounding variable.