Indeterminate colitis: the real story

PURPOSE: Up to one in five patients undergoing surgery for ulcerative colitis will have ambiguous histology, with features of both ulcerative colitis and Crohn's disease, and are categorized as having indeterminate colitis. We hypothesized that functional outcomes in indeterminate colitis patients undergoing ileal pouch-anal anastomosis are comparable with those of ulcerative colitis patients undergoing ileal pouch-anal anastomosis. METHODS: Physician-conducted interviews of 120 consecutive ileal pouch-anal anastomosis patients with a preoperative diagnosis of ulcerative colitis were reviewed, with a mean follow-up of 54 months. All colectomy specimens were reviewed by a single pathologist. Any changes in histologic diagnosis from ulcerative colitis to indeterminate colitis or Crohn's disease, frequency of postoperative complications, pouch function, and long-term postoperative medication usage were recorded. RESULTS: Although postoperative fistulas were more common in indeterminate colitis than ulcerative colitis (26 vs. 10 percent; P = 0.02, chi-squared), no indeterminate colitis patient required a permanent ileostomy as compared with six ulcerative colitis patients. Long-term functional results were similar. Overall, two-thirds of patients developed pouchitis. Ulcerative colitis and Crohn's disease patients were more likely to have had >3 episodes of pouchitis (58 and 72 percent) compared with indeterminate colitis patients (29 percent; P = 0.006, chi-squared). A greater number of Crohn's disease patients required maintenance oral antibiotic therapy (64 percent) to achieve satisfactory functional results compared with both indeterminate colitis and ulcerative colitis patients (20 and 28 percent; P = 0.014, chi-squared). CONCLUSIONS: Although ileal pouch-anal anastomosis patients with indeterminate colitis have more postoperative fistulas, long-term function is equal to that of ulcerative colitis patients and better than Crohn's disease patients. Ileal pouch-anal anastomosis should be offered to patients with indeterminate colitis and those with severe colitis in whom clear differentiation between indeterminate colitis and ulcerative colitis cannot be made.     

Biatrial multisite mapping of atrial premature complexes triggering onset of atrial fibrillation

Pulmonary veins are considered to be the most common origin of the focal activity that triggers the onset of atrial fibrillation (AF). However, little is known about the importance of ectopic activity located outside the pulmonary veins. This study included 45 patients (8 women and 37 men, mean age 55 ± 12 years) with paroxysmal (n = 25) and persistent (n = 20) AF in whom multisite mapping of the right and left atria was performed using a 64-electrode basket catheter (n = 21) or a noncontact mapping system (n = 24). Spontaneous or orciprenaline-induced atrial premature complexes (APCs) were mapped. In all, 94 AF onsets from 38 distinct foci in 30 patients were observed and analyzed. Of these foci, 20 (53%) were located in pulmonary veins and 18 (47%) were located outside the pulmonary veins in other parts of the atria. In 22 patients (73%), AF was reproducibly induced by APCs from a single focus (59 episodes). In 8 patients (27%), AF originated from 2 distinct foci (35 episodes). Additionally, 20 of 30 patients (67%) who developed AF had APCs in different locations not inducing AF. APCs inducing AF had shorter coupling intervals than APCs not inducing AF (307 ± 54 vs 409 ± 76 ms, p <0.001). This study showed that 47% of ectopic foci triggering the onset of AF were located outside the pulmonary veins in extravenous parts of the left atrium and the right atrium, and 27% of patients had AF onsets of bifocal origin. These data challenge the current opinion that extrapulmonary foci play a minor role in inducing AF.     

Phagocytosis and production of reactive oxygen species by peripheral blood phagocytes in patients with different stages of alcohol-induced liver disease: effect of acute exposure to low ethanol concentrations

BACKGROUND: In rodents, the development of alcoholic liver disease (ALD) after chronic alcohol feeding was shown to depend on the activity of enzymes that are necessary for production of reactive oxygen species (ROS) in phagocytes. The aim of this study was to determine the formation of ROS by resting and challenged phagocytes of patients with different stages of ALD in the presence of ethanol concentrations commonly found in the blood of alcohol abusers. PATIENTS AND METHODS: The release of ROS and the phagocytosis of bacteria by neutrophils and monocytes obtained from 60 patients, who were categorized in three groups due to the severity of ALD, were compared to that of 28 healthy controls. ROS release by these phagocytes was measured after challenging with endotoxin and the addition of ethanol (22 and 44 mM). RESULTS: Resting neutrophils but not monocytes from patients with severe stages of ALD produced significantly more ROS than those of healthy controls. Basal values of ROS production from neutrophils correlated closely to markers of the severity of ALD. ROS formation was depressed dose-dependently by ethanol in the healthy controls but not in alcohol abusers. CONCLUSIONS: Changes in the ROS metabolism of phagocytes found in this study might contribute to both the development of ALD and the impaired immune response occurring in patients with severe ALD.     

Herpes zoster as an immune restoration disease in AIDS patients during therapy including protease inhibitors

A prospective study to evaluate the incidence of herpes zoster (HZ) as an immune restoration disease in patients with AIDS during highly active antiretroviral therapy (HAART) was conducted in a series of 115 patients diagnosed with AIDS initiated on HAART between 1 January 2000 and 31 July 2001. Of these, a single dermatomal HZ episode occurred in 14 (12%) patients within one and 15 months of HAART (median eight months). The HZ patients were similar to the non-HZ patients in age, sex, and HIV transmission risk factor, but had a more advanced disease. Compared with the baseline values, the viral loads significantly (P<0.01) decreased, while the mean CD4+ T-cell counts increased by almost four-fold (P<0.01) in both groups at the time of the HZ episode (or equivalent in non-HZ), but remained below 400/mL in the HZ patients. HZ during HAART is an immunopathological consequence of the improvement of the host immuneresponse, correlating with the beginning of immune restoration.     

Reversal of granulocyte adherence to nylon fibers using local anesthetic agents: possible application to filtration leukapheresis

The effects of the cationic anesthetic agents tetracaine and lidocaine on granulocyte function, morphology, and adherence to nylon fibers were studied in an attempt to improve current methods of granulocyte collection by filtration leukapheresis (FL). When dissolved in acid- citrate-dextrose (ACD) plasma, these drugs significantly increased granulocyte elution from the fibers in a dose-related fashion. Granulocytes exposed to tetracaine and lidocaine remained more than 95% viable, retained normal bactericidal capacity after the drugs were washed from the cells, and had preserved membrane integrity, as evidenced by the normal ultrastructural appearance of tetracaine- exposed cells and an absence of leakage of lysozyme or lactic dehydrogenase. Granulocytes eluted with the anesthetic agents were rounded in shape with a reduction in the number of filopodial cytoplasmic projections and a relative absence of cytoplasmic vacuolization when compared to granulocytes eluted with ACD plasma alone. Dose-related inhibition of phagocytosis and adherence, which was largely reversible after washing the granulocytes, was noted. Greater than 95% of the lidocaine could be removed from the eluate with a single centrifugation and resuspension, indicating that granulocytes prepared by FL with anesthetic-enhanced elution could be potentially transfusable.     

Carotid artery disease: Stenting versus endarterectomy

Atherosclerotic carotid artery stenosis is a major cause of disabling stroke or death. Although carotid endarterectomy (CEA) is currently considered to be the standard of care for patients with a severe symptomatic stenosis and selected patients with an asymptomatic carotid stenosis, carotid angioplasty and stenting (CAS) is increasingly being used as an alternative treatment modality. This article briefly summarizes the current trial data on CEA and CAS. More importantly, potential risk factors for CEA and CAS are reviewed and the complementary role of these techniques in the management of the individual patient is discussed.     

Neutrophil activation and production of reactive oxygen species in pre-eclampsia

OBJECTIVE: To investigate neutrophil NADPH oxidase activation and subsequent production of reactive oxygen species (ROS) in pre-eclampsia. DESIGN: Baseline values and the activated response of neutrophils upon stimulation of the NADPH oxidase with the agonists was measured. Neutrophils from 17 third-trimester pre-eclamptic and 17 age- and gestation-matched normal pregnant women were examined. METHODS: Neutrophil ROS production was measured by both lucigenin- and luminol-derived chemiluminescence. The abundance of the various phox proteins was examined using Western blotting techniques. Lucigenin-derived ROS generation was significantly increased in neutrophils isolated from women with pre-eclampsia compared with normotensive controls in the case of both agonists [n-formyl-met-leu-phe (fMLP): pre-eclamptic 2.071 +/- 0.336 relative light units seconds (RLU.s) and normotensive 1.141 +/- 0.249 RLU.s, P = 0.035; phorbol-12-myristate-13-acetate (PMA): pre-eclamptic 34.954 +/- 2.634 RLU.s and normotensive 17.208 +/- 3.325 RLU.s, P = 0.0001]. Luminol-derived ROS generation was also significantly increased in the neutrophils isolated from the women with pre-eclampsia compared with the normotensive controls in the case of both agonists (fMLP: pre-eclamptic 1.955 +/- 0.316 RLU.s and normotensive 1.058 +/- 0.191 RLU.s, P = 0.023; PMA: pre-eclamptic 4.108 +/- 0.351 RLU.s and normotensive 3.073 +/- 0.332 RLU.s, P = 0.042). There were no differences between the relative abundance of the phox proteins in the two groups. CONCLUSIONS: Neutrophils isolated from women with pre-eclampsia during the third trimester showed increased sensitivity to agonist stimulation and produced significantly more ROS than age-matched normotensive controls. This was not due to an increased abundance of any of the phox proteins. Increased ROS production in pre-eclampsia may highlight a role for neutrophils in the oxidative stress and associated endothelial dysfunction that are characteristic of the condition.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.