Metastatic brain tumours in Northern Ireland: a retrospective review in a closed community with emphasis on short term quality of life

One hundred and nineteen consecutive patients with metastatic brain tumours who presented to the Provincial Neurosurgical Service in Northern Ireland were studied. The detection rate doubled after computerised tomography became available though the population in Northern Ireland over the years of study stayed relatively stable. Multiple tumours accounted for 38% while solitary tumours occurred mainly in the cerebellum or parietal lobe. Whereas 70% of patients presented with features of increased intracranial pressure and or lateralizing neurological signs, 20% had only vague symptoms. The primary site was lungs in a third of cases but in 33 cases (27.5%), the site of origin remained unknown. 42% of those 76 cases operated were adenocarcinoma. More than 80% of these patients in whom excision of the tumours were done, had a better quality of life at one month compared with improvement in only a third after biopsy.     

Inhibition of bleomycin-induced cellular DNA strand scission by 1,10-phenanthroline.

Inhibition by 1,10-phenanthroline of cellular DNA strand scission induced by the antitumor antibiotic bleomycin in Ehrlich ascites tumor cells was studied. DNA alkaline elution was performed on cells after 1-hr bleomycin treatments. Pretreatment for 24 hr with initial 1,10-phenanthroline concentrations of 0.2 nmol/10(5) cells, which depletes cells of ferritin iron by 80%, had no consistent effect on bleomycin strand breakage. However, simultaneous treatment with 3.1 nmol of 1,10-phenanthroline/10(5) cells and with bleomycin concentrations from 5 to 25 microM decreased both apparent double-stranded breaks and random breakage. When cells were treated with both 3.1 nmol of 1,10-phenanthroline/10(5) cells and 25 microM bleomycin, washed free of both drugs, and incubated at 35 degrees for 1 hr, the resulting breakage was equivalent to that found in cells treated with bleomycin only. When the combination treatment was extended to 4 hr, cell washing and reincubation resulted in increased strand scission, as compared with strand scission in cells treated with bleomycin only. Growth inhibition by bleomycin was not affected appreciably by temporary suppression of DNA strand breakage activity.     

Performance of risk indices for identifying low bone density in postmenopausal women

OBJECTIVE: To examine the ability of 4 published osteoporosis risk indices to identify women with low bone density. SUBJECTS AND METHODS: Subjects included postmenopausal women 45 years and older consecutively recruited from US clinics, women from general practice centers in The Netherlands (age range, 50-80 years), women in the Rotterdam Study (The Netherlands) 55 years and older, and women aged 55 to 81 years old screened for a clinical trial of alendronate. Bone mineral density (BMD) was measured at the femoral neck or lumbar spine; T scores represent the number of SDs below the mean for young healthy women. One risk index was calculated from age and weight; the other risk indices included up to 4 additional variables obtained by questionnaire. We calculated the sensitivity and specificity for identifying women with BMD T scores of -2.5 or less or -2.0 or less in the US clinic sample and created 3 risk categories, using each of the 4 indices. RESULTS: Data were available for 1102 women from the US clinic sample, 3374 women in the Rotterdam Study, 23,833 women screened for a clinical trial of alendronate, and 4204 women from general practice centers in The Netherlands. Specificity for identifying BMD T scores of -2.5 or less ranged from 37% to 58% (depending on risk index) when sensitivity was approximately 90%. The prevalence of osteoporosis (defined as T scores < or = -2.5) differed widely across the 3 risk categories, ranging from 2% to 4% for the low-risk category to 47% to 61% for the high-risk category in the US clinic sample. For spine BMD in the US clinic sample, the prevalence of T scores of -2.5 or less ranged from 7% (low risk) to 38% (high risk). The large differences in prevalence across risk categories were consistent across the other 3 samples of postmenopausal women in the United States and The Netherlands for all 4 risk indices. CONCLUSIONS: We recommend measuring BMD in women who are classified as having an increased risk of osteoporosis by using any of these risk indices because all 4 indices appear to predict low bone mass equally well. The Osteoporosis Self-assessment Tool index is easiest to calculate and therefore may be most useful in clinical practice.     

Prevention of catheter-related blood stream infection

PURPOSE OF REVIEW: Catheter-related blood stream infections are a morbid complication of central venous catheters. This review will highlight a comprehensive approach demonstrated to prevent catheter-related blood stream infections. RECENT FINDINGS: Elements of prevention important to inserting a central venous catheter include proper hand hygiene, use of full barrier precautions, appropriate skin preparation with 2% chlorhexidine, and using the subclavian vein as the preferred anatomic site. Rigorous attention needs to be given to dressing care, and there should be daily assessment of the need for central venous catheters, with prompt removal as soon as is practicable. Healthcare workers should be educated routinely on methods to prevent catheter-related blood stream infections. If rates remain higher than benchmark levels despite proper bedside practice, antiseptic or antibiotic-impregnated catheters can also prevent infections effectively. A recent program utilizing these practices in 103 ICUs in Michigan resulted in a 66% decrease in infection rates. SUMMARY: There is increasing recognition that a comprehensive strategy to prevent catheter-related blood stream infections can prevent most infections, if not all. This suggests that thousands of infections can potentially be averted if the simple practices outlined herein are followed.     

Evaluation of the posttraumatic growth inventory after severe burn injury in Western Australia: clinical implications for use

Purpose: Posttraumatic growth (PTG) is “the subjective experience of positive psychological change reported as a result of the struggle with trauma”. Very few studies have explored PTG after burn injury. The Posttraumatic Growth Inventory (PTGI) is a 21-item questionnaire which assesses five domains in which PTG has been found. First, the aim of this study was to assess how PTG presented after a severe burn, and second, whether it could be measured by the PTGI in Australian burn survivors.

Methods: A mixed method approach was used. Seventeen patients who had a severe burn injury at least 2 years previously were interviewed and completed the PTGI. The interviews were analyzed, then compared to the PTGI responses.

Results: PTG in burn survivors had similarities to PTG arising from other trauma. Burn-specific context such as heat intolerance and functional problems influenced the type of changes made. Barriers to PTG in relationships were related to guilt burden and visible scarring.

Conclusion: PTG presents similarly after burn to other trauma types, but has other features to consider when devising intervention strategies. The PTGI is a 5-min screening tool that adequately identifies the presence or absence of PTG in burn survivors in Western Australia, and can guide intervention.

• Implications for rehabilitation:

• The Posttraumatic Growth Inventory is a 5-min screening tool that adequately identifies the degree of PTG in burn survivors in Western Australia.

• It is a quick and easy tool to use to identify the need for clinical intervention.

• It will also evaluate the effectiveness of strategies designed to target PTG.

• A mean score of 2.5 can be used as a threshold to guide intervention strategy.

     

Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation Recipients

The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150?IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk, .16; 95% confidence interval, .1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350?IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P?=?.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV <350?IU/mL and those who started at CMV >350?IU/mL (44% versus 57%; P?=?.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P?=?.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR], .26; 95% confidence interval [CI], .1-.8; P?=?.02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P?<.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150?IU/mL is associated with a >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350?IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.     

Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model

We recently demonstrated that electroporation enhances transfection in a mouse wound-healing model. Keratinocyte growth factor (KGF) is an inducer of epithelial cell proliferation and differentiation and has been shown to be under expressed in the wounds of diabetic individuals. We hypothesized that KGF delivered into an excisional wound via naked DNA injection with subsequent electroporation would be a novel and potentially effective method to enhance wound closure in a diabetic mouse model. ELISA assays confirmed production of KGF protein in cultured mouse cells and RT-PCR assays confirmed KGF mRNA in skin samples taken from mice. In all, 32 genetically diabetic mice were given two identical excisional wounds of their dorsum and split into two groups with one group receiving KGF DNA injection and electroporation with the other group receiving no treatment. Over 90% of wounds healed in the presence of KGF and electroporation versus 40% in the untreated group by day 12. Histological analysis of the wounds demonstrated that untreated wounds contained microulcers with thin or incomplete epithelium with unresolved inflammation as compared to treated wounds where intact and mature epithelium was observed. Taken together these findings suggest that a single injection of KGF DNA encoded on a plasmid coupled with electroporation improves and accelerates wound closure in a delayed wound-healing model.     

Genetic Association of Nonsynonymous Variants of the IL23R with Familial and Sporadic Inflammatory Bowel Disease in Women

Purpose To replicate the association of IL23R R381Q (rs11209026) with inflammatory bowel disease (IBD), examine the effect of the two nonsynonymous variations, Q3H and L310P, on IBD, and to study gender distribution of these variants in IBD patients. Results IL23R R381Q was associated with Crohn’s disease (CD) (P = 0.010), but not with ulcerative colitis (UC); L310P was associated with UC (P = 0.004), but not with CD; no association was observed for Q3H with CD or UC. A female-specific association of R381Q with CD (P = 0.041), and of L310P with UC (P = 0.008) was observed. Conclusion We replicated the association of IL23R R381Q with CD but not UC, and we observed an association of L310P with UC, but not CD, in a central Pennsylvania population. Further analysis of the distribution of IL23R variants revealed that these effects were largely female-specific. The results suggest that IL23R R381Q confers protection against CD and that L310P confers protection against UC in females.