<Emphasis Type="Italic">SMAD4</Emphasis> - Molecular gladiator of the TGF-β signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to <Emphasis Type="Italic">KRAS</Emphasis>proto-oncogene

Background  

The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype.     

Necrotizing haemorrhagic pneumonia proves fatal in an immunocompetent child due to Panton–Valentine Leucocidin, toxic shock syndrome toxins 1 and 2 and enterotoxin C-producing Staphylococcus aureus

Panton–Valentine leucocidin (PVL) toxin-producing strains of Staphylococcus aureus ( S. aureus ) are associated with skin abscesses and furunculosis, with necrotizing pneumonia being a relatively rare problem. Here, we describe a fatal case of necrotizing pneumonia in a 14-year-old child who presented initially with sore throat and pyrexia. He deteriorated rapidly, developing hypotension, multiple organ failure and purpura fulminans. S. aureus was isolated from the tracheal aspirate, which was found to be positive for PVL, toxic shock syndrome toxins (TSST) 1 and 2 and staphylococcal enterotoxin C (SEC). It was postulated that purpura fulminans and toxic shock syndrome were a result of the abovementioned exotoxins.
Conclusion: This case highlights the emergence of PVL-positive community-acquired S. aureus infection and association of purpura fulminans with superantigens. Practitioners should be aware of this illness in order to initiate appropriate treatment.     

An update on the management of Wilms' tumour.

AIMS: To review the management of Wilms' tumour. METHODS: A search of the literature was performed using the PubMed database (1966 to May 2006) with the search terms 'Wilms' and either 'tumour/tumor' or 'cancer' or 'carcinoma'. This was augmented by manual searches of publications. FINDINGS: The success of clinical trials in Wilms' tumour patients over the past 30 years has led to an overall survival of 85% and the introduction of less aggressive chemotherapeutic regimes for patients. Large randomised controlled trials have been published on the management of Wilms' tumour by various collaborative groups, including the National Wilms' Tumour Study Group (NWTSG) in North America and the Société Internationale d'Oncologie Pédiatrique (SIOP) plus the United Kingdom Children's Cancer Study Group (UKCCSG) in Europe. CONCLUSIONS: Controversy exists as to the best approach to the management of these children with regard to neoadjuvant chemotherapy. Challenges remain in the identification of histological and molecular risk factors for the stratification of treatment intensity.     

Comparative activities of doripenem versus isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp. with characterized beta-lactamases

Doripenem (S-4661), a new parenteral carbapenem, was tested against over 250 clinical isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp., selected or derived for their beta-lactamase expression characteristics. Imipenem, meropenem, and ertapenem were tested as comparators, along with cephalosporins and piperacillin-tazobactam, by using National Committee for Clinical Laboratory Standards agar dilution methodology. Doripenem MICs were from 0.03 to 0.25 microg/ml for Klebsiella isolates, irrespective of the presence of extended-spectrum beta-lactamases (ESBLs) or plasmid-mediated AmpC or hyperproduced K1 beta-lactamase. Similarly, MICs of doripenem for both AmpC-inducible and -derepressed Enterobacter isolates were 0.06 to 0.5 microg/ml. ESBL production did not raise the MICs of doripenem for Escherichia coli transconjugants, and studies with known expression mutants confirmed that neither inducible nor depressed AmpC beta-lactamase expression was protective in Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, or Morganella morganii. In all of these respects, doripenem resembled meropenem and imipenem, whereas the MICs of ertapenem were raised (but still < or =1 microg/ml) for many ESBL-producing klebsiellas and AmpC-derepressed E. cloacae and C. freundii strains. Resistance to all carbapenems, including doripenem (MICs of mostly 16 to 64 microg/ml, compared with 0.25 to 1 microg/ml for typical strains), was seen in Acinetobacter isolates with metallo-beta-lactamases or OXA-carbapenemases. Isolates of Klebsiella and Serratia spp. with IMP, KPC, and SME beta-lactamases also were resistant to doripenem (MICs, 8 to >64 microg/ml) and to other carbapenems, although the continued apparent susceptibility (MICs, < or =0.5 microg/ml) of E. coli derivatives with cloned IMP-1 and NMC-A beta-lactamases suggested that carbapenem resistance might require other factors besides the enzymes.     

Ten-year trends in traumatic injury mechanisms and outcomes: A trauma registry analysis

Background

The Oklahoma Trauma Registry (OTR) collects data from all state-licensed acute care hospitals. This study investigates trends and outcomes of trauma in Oklahoma using OTR.