Citations

Abstract One hundred and ninety patients with Clostridium difficile toxin-associated colitis (CTAC) or pseudomembranous colitis (PMC) were identified, from microbiology records, disease index and proctoscopy service records, and studied retrospectively. CTAC was associated with cephalosporin antibiotic administration in 70 per cent of the patients. CTAC developed postoperatively in 108 patients after all types of surgery with no preponderance for abdominal surgery. Identification of cytotoxin in stool samples was the primary diagnostic test in 81 per cent of patients but cytotoxin was isolated in 98 per cent of all patients. Pseudomembranes visible on proctoscopy established the diagnosis in 19 per cent of patients and were more commonly seen in severe colitis (71 per cent) than in mild colitis (23 per cent). CTAC responded similarly to oral vancomycin and metronidazole with a relapse rate of 20–23 per cent, respectively. With its association with cephalosporin administration, CTAC is likely to occur with increasing frequency in surgical practice. Oral metronidazole is an effective, cheap, alternative to vancomycin therapy.

Abstract Pretreatment cytogenetics is a known predictor of outcome in hematologic malignancies. However, its usefulness in adult acute lymphoblastic leukemia (ALL) is generally limited to the presence of the Philadelphia (Ph) chromosome because of the low incidence of other recurrent abnormalities. We present centrally reviewed cytogenetic data from 1522 adult patients enrolled on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. The incidence and clinical associations for more than 20 specific chromosomal abnormalities are presented. Patients with a Ph chromosome, t(4;11)(q21;q23), t(8;14)(q24.1;q32), complex karyotype (5 or more chromosomal abnormalities), or low hypodiploidy/near triploidy (Ho-Tr) all had inferior rates of event-free and overall survival when compared with other patients. In contrast, patients with high hyperdiploidy or a del(9p) had a significantly improved outcome. Multivariate analysis demonstrated that the prognostic relevance of t(8;14), complex karyotype, and Ho-Tr was independent of sex, age, white cell count, and T-cell status among Ph-negative patients. The observation that Ho-Tr and, for the first time, karyotype complexity confer an increased risk of treatment failure demonstrates that cytogenetic subgroups other than the Ph chromosome can and should be used to risk stratify adults with ALL in future trials.

OBJECTIVE. We examined the effect of activity-enhancing screen devices on children's energy expenditure compared with performing the same activities while seated. Our hypothesis was that energy expenditure would be significantly greater when children played activity-promoting video games, compared with sedentary video games. METHODS. Energy expenditure was measured for 25 children aged 8 to 12 years, 15 of whom were lean, while they were watching television seated, playing a traditional video game seated, watching television while walking on a treadmill at 1.5 miles per hour, and playing activity-promoting video games. RESULTS. Watching television and playing video games while seated increased energy expenditure by 20 ± 13% and 22 ± 12% above resting values, respectively. When subjects were walking on the treadmill and watching television, energy expenditure increased by 138 ± 40% over resting values. For the activity-promoting video games, energy expenditure increased by 108 ± 40% with the EyeToy (Sony Computer Entertainment) and by 172 ± 68% with Dance Dance Revolution Ultramix 2 (Konami Digital Entertainment). CONCLUSIONS. Energy expenditure more than doubles when sedentary screen time is converted to active screen time. Such interventions might be considered for obesity prevention and treatment.

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer’s disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders.

Chromosomal integration enables human immunodeficiency virus (HIV) to establish a permanent reservoir that can be therapeutically suppressed but not eradicated. Participation of cellular proteins in this obligate replication step is poorly understood. We used intensified RNA interference and dominant-negative protein approaches to show that the cellular transcriptional coactivator lens epithelium–derived growth factor (LEDGF)/p75 (p75) is an essential HIV integration cofactor. The mechanism requires both linkages of a molecular tether that p75 forms between integrase and chromatin. Fractionally minute levels of endogenous p75 are sufficient to enable integration, showing that cellular factors that engage HIV after entry may elude identification in less intensive knockdowns. Perturbing the p75-integrase interaction may have therapeutic potential.

MRP1 (multidrug resistance protein 1) couples ATP binding/hydrolysis at its two non-equivalent NBDs (nucleotide-binding domains) with solute transport. Some of the NBD1 mutants, such as W653C, decreased affinity for ATP at the mutated site, but increased the rate of ATP-dependent solute transport. In contrast, other NBD1 mutants, such as K684L, had decreased ATP binding and rate of solute transport. We now report that mutations of the Walker A lysine residue, K684L and K1333L, significantly alter the tertiary structure of the protein. Due to elimination of the positively charged group and conformational alterations, the K684L mutation greatly decreases the affinity for ATP at the mutated NBD1 and affects ATP binding at the unmutated NBD2. Although K684L-mutated NBD1 can bind ATP at higher concentrations, the bound nucleotide at that site is not efficiently hydrolysed. All these alterations result in decreased ATP-dependent solute transport to approx. 40% of the wild-type. In contrast, the K1333L mutation affects ATP binding and hydrolysis at the mutated NBD2 only, leading to decreased ATP-dependent solute transport to approx. 11% of the wild-type. Consistent with their relative transport activities, the amount of vincristine accumulated in cells is in the order of K1333L≥CFTR (cystic fibrosis transmembrane conductance regulator)>K684L⋙wild-type MRP1. Although these mutants retain partial solute transport activities, the cells expressing them are not multidrug-resistant owing to inefficient export of the anticancer drugs by these mutants. This indicates that even partial inhibition of transport activity of MRP1 can reverse the multidrug resistance caused by this drug transporter.