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1.  Incidence of symptomatic brain metastasis following radical radiotherapy for non-small cell lung cancer: is there a role for prophylactic cranial irradiation? 
The British Journal of Radiology  2012;85(1020):1546-1550.
Brain metastases following radical radiotherapy for non-small cell lung cancer (NSCLC) are a recognised phenomenon; however, the incidence of symptomatic brain metastasis is currently unknown. The aim of the study was to identify the number of patients, staged in accordance with National Institute for Health and Clinical Excellence (NICE) guidance, who developed symptomatic brain metastasis following radical radiotherapy. There are two aims: to evaluate NICE guidance; and to provide vital information on the likely benefit of prophylactic cranial irradiation (PCI) in reducing neurological symptoms from brain metastasis.
A retrospective review of 455 patients with NSCLC who had undergone radical radiotherapy in 2009 and 2010 was performed. Computer-based systems were used to identify patient and tumour demographics, the staging procedures performed and whether brain imaging had identified brain metastasis in the follow-up period.
The total number of patients with brain metastasis within 6 months was 3.7%. The proportion of brain metastasis within 6 months in Stage I, II and III NSCLC throughout both years was 2.8%, 1.0% and 5.7%, respectively. Within the follow-up period (median 16 months, range 6–30 months), the total number of patients who developed symptomatic brain metastasis was 7.9%.
Patients staged in accordance with NICE guidance, of whom only 7.7% underwent brain staging, have a minimal incidence of brain metastasis following radical radiotherapy. The number of patients developing symptoms from brain metastasis following radical radiotherapy may be less than the morbidity caused by PCI.
Advances in knowledge
This finding supports the NICE guidance and brings into question the potential benefit of PCI.
PMCID: PMC3611712  PMID: 22993386
2.  Genetic regulation of the ramA locus and its expression in clinical isolates of Klebsiella pneumoniae 
Tigecycline resistance has been attributed to ramA overexpression and subsequent acrA upregulation. The ramA locus, originally identified in Klebsiella pneumoniae, has homologues in Enterobacter and Salmonella spp. In this study, we identify in silico that the ramR binding site is also present in Citrobacter spp. and that Enterobacter, Citrobacter and Klebsiella spp. share key regulatory elements in the control of the romA–ramA locus. RACE (rapid amplification of cDNA ends) mapping indicated that there are two promoters from which romA–ramA expression can be regulated in K. pneumoniae. Correspondingly, electrophoretic binding studies clearly showed that purified RamA and RamR proteins bind to both of these promoters. Hence, there appear to be two RamR binding sites within the Klebsiella romA–ramA locus. Like MarA, RamA binds the promoter region, implying that it might be subject to autoregulation. We have identified changes within ramR in geographically distinct clinical isolates of K. pneumoniae. Intriguingly, levels of romA and ramA expression were not uniformly affected by changes within the ramR gene, thereby supporting the dual promoter finding. Furthermore, a subset of strains sustained no changes within the ramR gene but which still overexpressed the romA–ramA genes, strongly suggesting that a secondary regulator may control ramA expression.
PMCID: PMC3117140  PMID: 21514798
Klebsiella pneumoniae; romA; ramA; ramR; acrA; Tigecycline
3.  Diagnosis of tuberculosis in children: increased need for better methods. 
Emerging Infectious Diseases  1995;1(4):115-123.
In the last decade tuberculosis (TB) has reemerged as a major worldwide public health hazard with increasing incidence among adults and children. Although cases among children represent a small percentage of all TB cases, infected children are a reservoir from which many adult cases will arise. TB diagnosis in children usually follows discovery of a case in an adult, and relies on tuberculin skin testing, chest radiograph, and clinical signs and symptoms. However, clinical symptoms are nonspecific, skin testing and chest radiographs can be difficult to interpret, and routine laboratory tests are not helpful. Although more rapid and sensitive laboratory testing, which takes into account recent advances in molecular biology, immunology, and chromatography, is being developed, the results for children have been disappointing. Better techniques would especially benefit children and infants in whom early diagnosis is imperative for preventing progressive TB.
PMCID: PMC2626885  PMID: 8903180
4.  Two macroprolactinomas presenting with neurological signs. 
Macroprolactinomas commonly cause pressure effects on immediate parasellar structures, in particular on the optic chiasm to cause visual field defects. Pressure on more distant brain structures is rarely reported. We describe two massive prolactinomas presenting with neurological signs, including signs of hemiparesis which, to our knowledge, has not been reported previously.
PMCID: PMC1295113  PMID: 7769587
5.  Hepatoblastoma in an Adult with Biliary Obstruction and Associated Portal Venous Thrombosis 
HPB Surgery  1995;9(1):47-49.
We present a case of adult hepatoblastoma. This young female presented with severe acute cholangitis. Preoperative diagnosis was common bile duct (CBD) obstruction with portal vein thrombosis. On exploration she had a tumor mass in the CBD. The unusual features of this case are discussed in this report.
PMCID: PMC2443761  PMID: 8857454
6.  Retroviral integrase domains: DNA binding and the recognition of LTR sequences. 
Nucleic Acids Research  1991;19(4):851-860.
Integration of retroviral DNA into the host chromosome requires a virus-encoded integrase (IN). IN recognizes, cuts and then joins specific viral DNA sequences (LTR ends) to essentially random sites in host DNA. We have used computer-assisted protein alignments and mutagenesis in an attempt to localize these functions within the avian retroviral IN protein. A comparison of the deduced amino acid sequences for 80 retroviral/retrotransposon IN proteins reveals strong conservation of an HHCC N-terminal 'Zn finger'-like domain, and a central D(35)E region which exhibits striking similarities with sequences deduced for bacterial IS elements. We demonstrate that the HHCC region is not required for DNA binding, but contributes to specific recognition of viral LTRs in the cutting and joining reactions. Deletions which extend into the D(35)E region destroy the ability of IN to bind DNA. Thus, we propose that the D(35)E region may specify a DNA-binding/cutting domain that is conserved throughout evolution in enzymes with similar functions.
PMCID: PMC333721  PMID: 1850126

Results 1-6 (6)