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Biomedical subjects

John Edwards

Publications and source records attributed to John Edwards.

At least 19 recordsLinked to original sources
PubMed2007

Is there a role for therapeutic lobectomy for emphysema?

OBJECTIVE: The feasibility of performing a standard lobectomy in patients with non-small cell lung cancer (NSCLC) and severe heterogeneous emphysema whose respiratory reserve is outside standard operability guidelines has been described [Edwards JG, Duthie DJR, Waller DA. Lobar volume reduction surgery: a method of increasing the lung cancer resection rate in patients with emphysema. Thorax 2001;56:791-5; Korst RJ, Ginsberg RJ, Ailawadi M, Bains MS, Downey RJ, Rusch V, Stover D. Lobectomy improves ventilatory function in selected patients with severe COPD. Ann Thorac Surg 1998;66:898-902; Carretta A, Zannini P, Puglisi A, Chiesa G, Vanzulli A, Bianchi A, Fumagalli A, Bianco S. Improvement in pulmonary function after lobectomy for non-small cell lung cancer in emphysematous patients. Eur J Cardiothorac Surg 1999;15(5):602-7]. Postoperative lung function was better than predicted, attributable to the therapeutic benefit of deflation of the hemithorax. Our aim was to determine whether the physiological benefits of this approach were superior to conventional non-anatomical lung volume reduction surgery (LVRS) in similar patients. METHODS: A retrospective review of a single surgeon's experience identified 34 consecutive patients who underwent upper lobectomy for completely resected stage I-II NSCLC, and who had severe heterogeneous emphysema of apical distribution with a predicted postoperative FEV1 of less than 40%. Their perioperative characteristics, postoperative spirometry and survival of these cases were compared to 46 similar patients who underwent unilateral upper lobe LVRS during the same period. RESULTS: Data expressed as median (range). LVRS patients were significantly younger (59 years [39-70] vs 67 years [48-79] p<0.001), with more severe airflow obstruction (FEV(1) %pred 24 [12-60] vs 44 [17-54] p<0.001) and more heterogenous disease ('Q' score 4 [0.5-11.5] vs 7 [1-13] p=0.001) than the lobectomy group. No significant difference was found in median survival (88 vs 53 months, p=0.06). Lobectomy patients had a shorter air leak duration (5 days [2-36] vs 9 days [1-40], p=0.02) and hospital stay (8 days [3-63] vs 13 days [6-90] p=0.01). A significant correlation was found between pre-operative Q score and percentage improvement in FEV1 (r=-0.33, p=0.02). CONCLUSIONS: Lobectomy for lung cancer in patients in severe heterogenous chronic obstructive pulmonary disease is associated with similar improvement in airflow obstruction as conventional LVRS, but is associated with a shorter postoperative course. Lobectomy may therefore offer a therapeutic alternative to conventional LVRS in a selected population.

Adult↗
PubMed2006

Preparing for the unthinkable: emergency preparedness for the hematopoietic cell transplant program.

Emergencies come at the most inopportune times. Some are totally unexpected, others come with short warnings. Although rare, an emergency comes with the potential to wreak disaster and pose serious risk to the services provided to hematopoietic cell transplant (HCT) patients. Yet, the consequences of an emergency can be mitigated by thinking the unthinkable and having a plan for emergency preparedness in place. Each HCT center should develop a plan containing steps of mitigation, preparedness, response and recovery. This report provides the framework for a HCT-specific emergency preparedness plan that can be used by individual centers to develop customized guidelines on preparing for, responding to, and recovering from an emergency.

Disaster Planning↗
PubMed2005

Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables. Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.

Adenocarcinoma↗
PubMed2005

A genetic-algorithm approach to simulating human immunodeficiency virus evolution reveals the strong impact of multiply infected cells and recombination.

It has been previously shown that the majority of human immunodeficiency virus type 1 (HIV-1)-infected splenocytes can harbour multiple, divergent proviruses with a copy number ranging from one to eight. This implies that, besides point mutations, recombination should be considered as an important mechanism in the evolution of HIV within an infected host. To explore in detail the possible contributions of multi-infection and recombination to HIV evolution, the effects of major microscopic parameters of HIV replication (i.e. the point-mutation rate, the crossover number, the recombination rate and the provirus copy number) on macroscopic characteristics (such as the Hamming distance and the abundance of n-point mutants) have been simulated in silico. Simulations predict that multiple provirus copies per infected cell and recombination act in synergy to speed up the development of sequence diversity. Point mutations can be fixed for some time without fitness selection. The time needed for the selection of multiple mutations with increased fitness is highly variable, supporting the view that stochastic processes may contribute substantially to the kinetics of HIV variation in vivo.

Algorithms↗
PubMed2005

Computed tomographic colonography: prevalence, nature, and clinical significance of extracolonic findings in a community screening program.

OBJECTIVE: Colorectal neoplasia screening by computed tomographic colonography (CTC) may lead to the detection of incidental extracolonic findings. We report the prevalence and clinical significance of extracolonic pathology found within a community-based CTC screening program and the cost of clinical follow-up and further investigation of these findings. METHODS: A total of 432 asymptomatic subjects at an average risk of colorectal neoplasia, aged 50-69, had screening by CTC using a low radiation dose protocol. Axial images were prospectively examined for extracolonic lesions and those considered clinically relevant were followed up. All clinic visits and further investigations were tallied to calculate the incremental cost to the screening CTC. RESULTS: A total of 146 extracolonic lesions were detected in 118 (27.3%) subjects. Thirty-two (7.4%) subjects had clinically relevant extracolonic abnormalities and nine (2.1%) subjects may derive a clinical benefit from the detection of these lesions. A single CTC costed $171.12, and following up extracolonic findings resulted in an additional $24.37 (14.2%) per CTC. Limiting reporting to the aorta and kidneys would have reduced the number of subjects requiring follow-up to 14 (3.2%), and decreased the cost increment to 4.7% without detriment to clinical outcome. CONCLUSIONS: Extracolonic findings of screening CTC are common, but infrequent of clinical importance. The additional burden of following up these findings was modest and could have been further reduced if clear clinical and radiological criteria and pathways for their further investigation were defined.

Age Distribution↗
PubMed2005

Novel perspectives on mucormycosis: pathophysiology, presentation, and management.

Mucormycosis is a life-threatening fungal infection that occurs in immunocompromised patients. These infections are becoming increasingly common, yet survival remains very poor. A greater understanding of the pathogenesis of the disease may lead to future therapies. For example, it is now clear that iron metabolism plays a central role in regulating mucormycosis infections and that deferoxamine predisposes patients to mucormycosis by inappropriately supplying the fungus with iron. These findings raise the possibility that iron chelator therapy may be useful to treat the infection as long as the chelator does not inappropriately supply the fungus with iron. Recent data support the concept that high-dose liposomal amphotericin is the preferred monotherapy for mucormycosis. However, several novel therapeutic strategies are available. These options include combination therapy using lipid-based amphotericin with an echinocandin or with an azole (largely itraconazole or posaconazole) or with all three. The underlying principles of therapy for this disease remain rapid diagnosis, reversal of underlying predisposition, and urgent surgical debridement.

Antifungal Agents↗
PubMed2005

Molecular engineering approaches for DNA sequencing and analysis.

High-throughput DNA sequencing development for mutation screening and identification is essential to realize the goal of pharmacogenomics and personalized medicine, which will lead to a new era in clinical medicine and healthcare. Molecular engineering approaches to modify the building blocks of DNA by introducing functional groups for purification and detection has led to the development of high-throughput genetic analysis technologies. This review is focused on the following two DNA sequencing approaches. The first approach is based on the use of molecular affinity and mass spectrometry to perform quick and highly accurate mutation screening, heterozygote identification and insertion/deletion detection. The second approach is based on a sequencing-by-synthesis platform that has the potential for generating DNA sequencing data in a massive, parallel manner. The basic principles, fundamental challenges and methods of implementation of these exciting new technologies will be discussed.

Animals↗
PubMed2004

Cytosolic NADPH may regulate differences in basal Nox oxidase-derived superoxide generation in bovine coronary and pulmonary arteries.

Because systems controlled by basal NAD(P)H oxidase activity appear to contribute to differences in responses of endothelium-removed bovine coronary (BCA) and pulmonary (BPA) arteries to hypoxia, we characterized the Nox oxidases activities present in these vascular segments and how cytosolic NAD(P)H redox systems could be controlling oxidase activity. BPA generated approximately 60-80% more lucigenin (5 microM) chemiluminescence detectable superoxide than BCA. Apocynin (10 microM), a NAD(P)H oxidase inhibitor, and 6-aminonicotinamide (1 mM), a pentose phosphate inhibitor (PPP), both attenuated (approximately by 50-70%) superoxide detected in BPA and BCA. There was no significant difference in the expression of Nox2 or Nox4 mRNA or protein detected by Western blot analysis. NADPH and NADH increased superoxide in homogenates and isolated microsomal membrane fractions in a manner consistent with BPA and BCA having similar levels of oxidase activity. BPA had 4.2-fold higher levels of NADPH than BCA. The activity and protein levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting PPP enzyme generating cytosolic NADPH, were 1.5-fold higher in BPA than BCA. Thus BPA differ from BCA in that they have higher levels of G6PD activity, NADPH, and superoxide. Because both arteries have similar levels of Nox expression and activity, elevated levels of cytosolic NADPH may contribute to increased superoxide in BPA.

Acridines↗
PubMed2003

Changes in NO bioavailability regulate cardiac O2 consumption: control by intramitochondrial SOD2 and intracellular myoglobin.

The aim of this study was to investigate the significance of two intracellular scavengers of nitric oxide (NO): 1) superoxide dismutase (SOD) (SOD2) to scavenge intramitochondrial superoxide anion, and 2) cytosolic myoglobin (Mb) in the regulation of tissue O2 consumption. O2 consumption was measured in vitro using a Clark-type O2 electrode. SOD heterozygous mice (SODHZ) (n = 13) and SOD wild-type (SODWT) (n = 5) mice were used. Bradykinin (BK, 10-4 mol/l) reduced O2 consumption by 15% +/- 1 in hearts of SODHZ mice, which was significantly different from SODWT (reduced by 24 +/- 0.4%). Tiron significantly increased the inhibition of O2 consumption by BK in male mice from 15 +/- 1% (n = 13) to 29 +/- 1.2% (n = 4) at 10-4 mol/l concentration (P < 0.05). The effect of carbachol was similar to BK. S-nitroso-N-acetyl penicillamine (SNAP, 10-4 mol/l) reduced O2 consumption by 39 +/- 1.3% in hearts of SODHZ mice, which was not significantly different from SODWT. But at 10-7 mol/l, SNAP caused significantly less inhibition of O2 consumption in SODHZ mice. Mb knockout (MbKO; Mb wild-type n = 6) and (MbWT) mice (n = 6) were also used. Kidney cortex was studied as the negative control because it does not contain Mb. BK (10-4 mol/l) reduced O2 consumption by 32 +/- 2, 29 +/- 1, and 26 +/- 1% in the heart, skeletal muscle, and kidney of MbKO mice, which was also not significantly different from MbWT. SNAP (10-4 mol/l) reduced O2 consumption by 39 +/- 3, 42 +/- 4, and 46 +/- 2% in the heart, skeletal muscle, and kidney of MbKO mice, which was also not significantly different from MbWT. NG-nitro-l-arginine methyl ester (P < 0.05) inhibited the reduction in O2 consumption induced by BK in the MbKO mouse heart (15 +/- 1%), skeletal muscle (17 +/- 1%), and kidney (17 +/- 1%) as in the MbWT mice. These results suggest that the role of Mb as an intracellular NO scavenger is small, and the increase in mitochondrial superoxide in SODHZ mice may cause a decrease NO bioavailability and alter the control of myocardial O2 consumption by NO.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2003

Is there a role for pre-operative contrast-enhanced magnetic resonance imaging for radical surgery in malignant pleural mesothelioma?

OBJECTIVE: To assess the use of contrast-enhanced magnetic resonance imaging (CEMRI) in addition to computed tomography in the pre-operative assessment of patients for radical surgery in malignant pleural mesothelioma. METHODS: Over a 45-month period, 51 of 76 patients assessed (69 men and seven women), underwent extra-pleural pneumonectomy or radical pleurectomy/decortication. Post-operative pathological stage was correlated with radiological staging, with particular emphasis on tumour resectability. RESULTS: Seventeen (22%) patients were found on CEMRI to have unresectable, but histologically unconfirmed disease, not previously seen on CT. Fifty-one (67%) patients proceeded to radical surgery, but pathological nodal data were incomplete in three, so excluding these patients from further analyses. The median pre-operative interval after CEMRI was 17 days. Two patients were found to have unexpectedly extensive disease at thoracotomy, thus the sensitivity of CEMRI for prediction of resectability was 97%. Using the International Mesothelioma Interest Group system, tumour stage was correctly predicted by CEMRI in 48% of patients, but understaged in 50% of cases, largely due to the underestimation of pericardial involvement, but this did not affect resectability and had no significant effect on prognosis. Nodal stage was correctly identified in 60% of patients. CEMRI was successful in predicting pathological tumour stage T3 or less (sensitivity of 85%; specificity of 100%), but less so in identifying tumour stage T2 or less (sensitivity of 23%; specificity of 96%) or N2 nodal disease (sensitivity 66%; specificity 73%). CONCLUSIONS: CEMRI is most useful in the differentiation of T3 and T4 disease and may be unnecessary at earlier stages. Its multiplanar tumour localisation abilities are of value in the assessment of resectability. It is unlikely to contribute significantly to nodal staging, but it remains a valuable adjunct in the selection of patients for radical surgery.

Adult↗