Clenched-fist injury complicated by methicillin-resistant Staphylococcus aureus

Hand infections are a common sequela of clenched-fist injuries. The majority of these infections are due to Staphylococcus and Streptococcus species. Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly being isolated in Canadian health care facilities. In addition, MRSA now needs to be considered in community acquired hand infections that fail to respond to common empiric therapy. A 51-year-old man with MRSA due to a hand injury was treated successfully with vancomycin. The prevalence, mechanism of resistance and treatment of MRSA are briefly reviewed.     

Technique and early clinical results of endoscopic variceal ligation (EVL)

Summary Endoscopic variceal ligation (EVL) is a new technique designed to be used instead of sclerotherapy. Small elastic O rings ligate varices resulting in their strangulation and eradication. During a 12-month period, EVL was employed in 53 consecutive patients, of whom 36 (68%) had alcoholic cirrhosis 17 were Child-Pugh class A, 22 class B, and 14 class C. Varices were graded from I to IV and repeat treatments were given at 1–2 week intervals until the varices were eliminated. At follow-up ranging from 6–18 months (mean 11.5), 217 EVL treatment sessions had been performed. Of the 13 patients (24%) who died during the study, 11 died during the index hospitalization. Active bleeding was controlled in 19 of 21 patients (90%). Of 40 survivors 13 patients (33%) had 1–2 (mean 1.4) recurrent variceal bleeds while 34 patients had repeat EVL treatment. Elimination of distal varices was achieved in 26 and 7 had reduction of varices from grade III–IV to grade I–II or less. Eradication required a mean of 4.4 EVL sessions in Child's A and B patients and 7.0 sessions in Child's C patients (P<0.025). No significant treatment-related complications were observed. EVL appears to control active bleeding, is associated with a low incidence of non-bleeding complications, and may be used as an alternative to sclerotherapy.     

Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks,chromosomal instability,and reduced life span in mice

The Brca2 tumor-suppressor gene contributes to genomic stability, at least in part by a role in homologous recombinational repair. BRCA2 protein is presumed to function in homologous recombination through interactions with RAD51. Both exons 11 and 27 of Brca2 code for domains that interact with RAD51; exon 11 encodes eight BRC motifs, whereas exon 27 encodes a single, distinct interaction domain. Deletion of all RAD51-interacting domains causes embryonic lethality in mice. A less severe phenotype is seen with BRAC2 truncations that preserve some, but not all, of the BRC motifs. These mice can survive beyond weaning, but are runted and infertile, and die very young from cancer. Cells from such mice show hypersensitivity to some genotoxic agents and chromosomal instability. Here, we have analyzed mice and cells with a deletion of only the RAD51-interacting region encoded by exon 27. Mice homozygous for this mutation (called brca2(lex1)) have a shorter life span than that of control littermates, possibly because of early onsets of cancer and sepsis. No other phenotype was observed in these animals; therefore, the brca2(lex1) mutation is less severe than truncations that delete some BRC motifs. However, at the cellular level, the brca2(lex1) mutation causes reduced viability, hypersensitivity to the DNA interstrand crosslinking agent mitomycin C, and gross chromosomal instability, much like more severe truncations. Thus, the extreme carboxy-terminal region encoded by exon 27 is important for BRCA2 function, probably because it is required for a fully functional interaction between BRCA2 and RAD51.     

Exploring and embracing complexity in a distance-learning curriculum for physicians.

The recent pressures on clinical medicine such as the attention to medical error and the challenges of interdisciplinary care have also exerted pressure on health professions education. Educators must now gauge how to redesign education systems to adapt quickly to these disruptions. Sometimes disruptions can be self-inflicted, such as the VA National Quality Scholars Fellowship's decision to use interactive video (IV) as its primary medium for delivering the curriculum to its six sites around the nation. The authors describe how this disruption to their education system helped to fashion a learning environment that is adaptable. Along the journey from a classroom-based curriculum to an IV-based curriculum, the authors and others involved in the program learned the basic tenets of IV sessions, redefined the roles of the teachers and learners, and discovered an IV environment that functions as a complex adaptive learning system. This distance-learning curriculum can be a model for other health professions education, since it starts with simple rules, changes from within, has a tolerance for unpredictability, and continually moves forward and transforms itself despite tension.     

Sequence analysis of an isolate from a fatal human infection of Australian bat lyssavirus

Australian bat lyssavirus (ABLV), which occurs in pteropid and insectivorous bat populations, causes a rabies-like encephalitis in infected humans. We report the first complete sequence of an ABLV isolate obtained from a human who developed symptoms 27 months after being bitten by an infected flying fox. This isolate is the smallest lyssavirus to be sequenced, with a size of 11,918 nucleotides. Analyses of previously unsequenced regions and the complete genome confirm its close relationship with classical rabies viruses. In addition, a leucine zipper-like motif, not present in the other lyssaviruses, was found in the conserved domain I of the polymerase protein. This is the first report of a lyssavirus to vary in an 11-nucleotide, strictly conserved, complementary terminal sequence. This region is thought to encode important cis-acting regulatory signals; ABLV variation indicates a greater degree of flexibility than was thought for lyssaviruses in this region. A comparison of the pteropid and insectivorous isolates of ABLV indicates considerable differences between the two viruses. If the divergence of the two occurred on the Australian mainland, ABLV may have been endemic to Australia well before European colonisation.     

Systematic interindividual differences in neurobehavioral impairment from sleep loss: evidence of trait-like differential vulnerability

OBJECTIVES: To investigate interindividual differences in neurobehavioral deficits during sleep deprivation, and to establish to what extent the neurobehavioral responses to sleep loss are a function of sleep history versus trait-like differential vulnerability. DESIGN: Individuals were exposed to sleep deprivation on 3 separate occasions in order to determine the stability of interindividual differences in neurobehavioral impairment. SETTING: The sleep-deprivation experiments were conducted under standardized laboratory conditions with continuous monitoring of wakefulness. Each subject underwent a laboratory-adaptation session before entering the sleep-deprivation phase of the study. PARTICIPANTS: A total of 21 healthy adults (aged 21-38 years) completed the experiment. INTERVENTIONS: Subjects came to the laboratory 3 times at intervals of at least 2 weeks. During each laboratory session, they underwent neurobehavioral testing every 2 hours during 36 hours of total sleep deprivation, which was preceded by baseline sleep and followed by recovery sleep. In the week prior to each sleep-deprivation session and on the baseline night in the laboratory, subjects were required to either restrict their sleep to 6 hours per day (prior sleep restriction condition) or to extend their time in bed to 12 hours per day (prior sleep extension condition), so as to experimentally manipulate sleep history (in randomized counterbalanced order). RESULTS: There was strong evidence that interindividual differences in neurobehavioral deficits during sleep deprivation were systematic and trait-like. The magnitude of interindividual variability was substantial relative to the magnitude of the effect of prior sleep restriction (which on average involved a reduction of 4.1 hours sleep per day, compared to prior sleep extension, for 7 days). Overall, interindividual differences were not explained by subjects' baseline functioning or a variety of other potential predictors. Interindividual variability clustered on 3 distinct neurobehavioral dimensions: self-evaluation of sleepiness, fatigue, and mood; cognitive processing capability; and behavioral alertness as measured by sustained attention performance. CONCLUSIONS: Neurobehavioral deficits from sleep loss varied significantly among individuals and were stable within individuals. Interindividual differences in neurobehavioral responses to sleep deprivation were not merely a consequence of variations in sleep history. Rather, they involved trait-like differential vulnerability to impairment from sleep loss, for which neurobiologic correlates have yet to be discovered.     

Calorie restriction extends yeast life span by lowering the level of NADH

Calorie restriction (CR) extends life span in a wide variety of species. Previously, we showed that calorie restriction increases the replicative life span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase. Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR.