Long term results of surgery versus continuous hyperfractionated accelerated radiotherapy (CHART) in patients aged >70 years with stage 1 non-small cell lung cancer.
Patients with T1N0 non-small cell lung cancer (NSCLC) are preferably treated by anatomic lobectomy. However, not all such patients are suitable for lobectomy due to their age or co-morbidity. Our aim was to determine the results obtained following lobectomy, wedge resection (WR) or continuous hyperfractionated accelerated radiotherapy (CHART) in patients aged >70 years.



Two hundred and fifteen consecutive patients aged >70 years, with pathologic stage 1 NSCLC in our unit between 1991 and 2001 were studied. Of these patients, 149 had a lobectomy, 47 had a WR and 19 had CHART. Follow-up was 100% complete.



Analysis demonstrated the WR and CHART patients to have reduced pulmonary function (FEV(1) 59% and 52%, respectively, of predicted vs. 76%, P<0.001) when compared to the lobectomy group but there were no differences among the groups with regard to mean age and histologic tumour type. There were no operative mortality among patients after WR; however, a 2.7% 30-day operative mortality among patients undergoing lobectomy (P=0.29). Kaplan-Meier survival curves at 1 and 5 years for patients undergoing WR, lobectomy and CHART was 98% and 74% vs. 97% and 68% vs. 80% and 39%, respectively (P=0.0484). The frequency of local/regional recurrence in the WR group (19.1%) was not significantly higher than in the lobectomy group (18.4%, P=0.38) when compared to the CHART group (27%, P=0.07).



Loco-regional recurrence and survival after WR and lobectomy in elderly patients with stage I NSCLC are comparable. Although the numbers are small, these data suggest that CHART is a reasonable treatment option for those who are not suitable candidates for surgery.

title: Beating-heart mitral valve surgery in patients with poor left ventricular function.
abstract: Mitral valve surgery in the presence of poor left ventricular (LV) function is associated with higher mortality. One surgeon's (S. K. N.) evolving practice of mitral valve surgery on the beating heart using normothermic cardiopulmonary bypass (CPB) in a cohort of patients is described.



Between July 2000 and December 2002, 23 patients (13 men, 10 women; mean age 68.6 +/- 4.8 years; range: 54-81 years) with mitral regurgitation and LV ejection fraction <30% undergoing isolated mitral valve repair (n = 4) or replacement (n = 19) were investigated. All patients received maximal drug therapy. Among patients, 17 were in NYHA class III, and six in class IV.



The mean duration of follow up was 17 +/- 14 months, and was complete for all survivors. The visual field of the on-pump beating heart was equal to that of conventional valvular surgery, and technical accuracy was not compromised. The mean ICU and hospital stays were 2.4 +/- 1.3 days and 8.9 +/- 2.6 days, respectively. Mean CPB time was 74.3 +/- 14.8 min. Thirty-day mortality was significantly lower (8.7%) when compared to mean Euroscore-predicted mortality for this high-risk group (16.9%; p <0.001). The medium-term one- and two-year survivals were 87% and 78%, respectively. Mean NYHA class was improved, from 3.6 +/- 0.5 preoperatively to 1.9 +/- 0.7 at follow up (p = 0.037).



On-pump, beating-heart mitral valve surgery is a good option in patients with poor LV function, and is advantageous as conditions for the heart are more physiological with a beating tonus than with cardioplegia.

title: Pulmonary adenocarcinoma is associated with poor long-term survival after surgical resection. Effect of allogeneic blood transfusion.
abstract: The significance of allogeneic blood transfusion in the prognosis of patients with nonsmall lung carcinoma (NSCLC) remains controversial. Reports have suggested that patients with adenocarcinoma have a worse prognosis from cancer than patients with squamous cell carcinoma (SCC), but this evidence is lacking in NSCLC. The objective of the current study was to elucidate the correlation between perioperative allogeneic blood transfusion and the prognosis in patients with adenocarcinoma and SCC.



The study group comprised 329 consecutive patients (172 men and 157 women) with a mean age of 67 years who underwent lung resection between 1996 and 2003 in 1 unit. The clinicopathologic and survival data were compared between 62 patients (42.7%) with adenocarcinoma and 58 patients (48.3%) with SCC who received a perioperative blood transfusion and 83 patients (57.3 %) with adenocarcinoma and 126 patients (61.3%) with SCC who did not.



The overall surgical mortality rate was 3.9% (13 deaths). The median surgical blood loss was 380 mL (range, 125-4500 mL). The mean blood transfusion received was 1.9 U (range, 0-8 U). The overall actuarial 1, 3, and 5-year survival rates in the adenocarcinoma and SCC groups were 82.3%, 49.6%, and 19.4% and 87.9%, 71.7%, and 32.7%, respectively (P = 0.021). Multivariate analysis demonstrated that the factors that appeared to be independent prognostic factors in both groups were T-classification (P < 0.001), lymph node metastasis (P < 0.001), and postoperative complications (P = 0.029). Perioperative blood transfusion was not an independent prognostic indicator in either group.



The current study demonstrated that long-term survival in patients with adenocarcinoma of the lung was significantly worse compared with patients with SCC, but was independent of allogeneic perioperative blood transfusion. The results reaffirmed the importance of tumor invasion and lymph node involvement in the overall poor prognosis of these patients.

title: Histone-like protein HU from Deinococcus radiodurans binds preferentially to four-way DNA junctions.
abstract: The histone-like protein HU from Escherichia coli is involved in DNA compaction and in processes such as DNA repair and recombination. Its participation in these events is reflected in its ability to bend DNA and in its preferred binding to DNA junctions and DNA with single-strand breaks. Deinococcus radiodurans is unique in its ability to reconstitute its genome from double strand breaks incurred after exposure to ionizing radiation. Using electrophoretic mobility shift assays (EMSA), we show that D.radiodurans HU (DrHU) binds preferentially only to DNA junctions, with half-maximal saturation of 18 nM. In distinct contrast to E.coli HU, DrHU does not exhibit a marked preference for DNA with nicks or gaps compared to perfect duplex DNA, nor is it able to mediate circularization of linear duplex DNA. These unexpected properties identify DrHU as the first member of the HU protein family not to serve an architectural role and point to its potential participation in DNA recombination events. Our data also point to a mechanism whereby differential target site selection by HU proteins is achieved and suggest that the substrate specificity of HU proteins should be expected to vary as a consequence of their individual capacity for inducing the required DNA bend.

title: Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal.
abstract: The DNA binding subunit of the transcription factor NF-kappa B, p50, has been cloned. p50 appears to be synthesized as a larger protein that is then processed to its functional size. Sequence analysis reveals remarkable homology for over 300 amino acids at the amino-terminal end to the oncogene v-rel, its cellular homolog c-rel, and the Drosophila maternal effect gene dorsal. This establishes NF-kappa B as a member of the rel family of proteins, all of which display nuclear-cytosolic translocation. Protein sequence from the p65 polypeptide has established that it is not encoded in the same mRNA as p50. However, p65 appears homologous to c-rel, suggesting that c-rel may form heterodimers with p50 and rel may include a homodimerization motif.

title: Hypertrophic cardiomyopathy with preexcitation: insights from noninvasive electrocardiographic imaging (ECGI) and catheter mapping.
abstract: Hypertrophic Cardiomyopathy and Preexcitation.



Fasciculoventricular pathway has been described as an unusual variant of preexcitation. Electrocardiographic imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization.



We present a case of an 18-year-old male with hypertrophic cardiomyopathy (HCM) and an electrocardiogram (ECG)-based diagnosis of Wolff-Parkinson-White (WPW) syndrome, who underwent a noninvasive ECGI study to image ventricular activation, followed by an electrophysiology study (EPS). The ECGI electroanatomic isochrone map showed early activation of the epicardial aspect of the atrioventricular (A-V) groove and an aberrant posterior-base-to-apex progression of activation in the left ventricular (LV) epicardium. The EPS showed a likely fasciculoventricular pathway (FVP) without any inducible tachycardia.



While FVP has been described before, this is the first report of detailed quantitative three-dimensional characterization of electrical activation sequence of a heart with this type of preexcitation, using a novel noninvasive imaging modality (ECGI). In spite of abnormal ventricular activation, the EPS demonstrated that the FVP is not capable of supporting reentrant supraventricular tachycardia or rapidly conducted atrial fibrillation.

title: Natalizumab for active Crohn's disease.
abstract: In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by alpha4 integrins.



We conducted a double-blind, placebo-controlled trial of the alpha4 integrin-specific humanized monoclonal antibody natalizumab in 248 patients with moderate-to-severe Crohn's disease. Patients were randomly assigned to receive one of four treatments: two infusions of placebo; one infusion of 3 mg of natalizumab per kilogram of body weight, followed by placebo; two infusions of 3 mg of natalizumab per kilogram; or two infusions of 6 mg of natalizumab per kilogram. Infusions were given four weeks apart. Outcomes included changes in scores for the Crohn's Disease Activity Index (higher scores indicate more severe disease), the health-related quality of life, and C-reactive protein levels.



The group given two infusions of 6 mg of natalizumab per kilogram did not have a significantly higher rate of clinical remission (defined by a score of less than 150 on the Crohn's Disease Activity Index) than the placebo group at week 6 (the prospectively defined primary end point in the efficacy analysis). However, both groups that received two infusions of natalizumab had higher remission rates than the placebo group at multiple time points. Natalizumab also produced a significant improvement in response rates (defined by a reduction of at least 70 points in the score on the Crohn's Disease Activity Index). The highest remission rate was 44 percent and the highest response rate was 71 percent (at week 6 in the group given two infusions of 3 mg per kilogram). Overall, the two infusions of 6 mg of natalizumab per kilogram and of 3 mg per kilogram had similar effects. The quality of life improved in all natalizumab groups; C-reactive protein levels improved in groups receiving two infusions of natalizumab. The rates of adverse events were similar in all four groups.



Treatment with the selective adhesion-molecule inhibitor natalizumab increased the rates of clinical remission and response, improved the quality of life and C-reactive protein levels, and was well tolerated in patients with active Crohn's disease.

title: Correlation of macular thickness and posterior hyaloid change following bevacizumab and triamcinolone in diffuse diabetic macular edema in middle-aged patients
abstract: To compare changes in posterior vitreous detachment (PVD) following intravitreal injection of bevacizumab and triamcinolone in diffuse diabetic macular edema in middle-aged type 2 diabetes patients and to correlate this change with change in central macular thickness (CMT).  Fifteen consecutive patients treated by intravitreal bevacizumab (group A) and ten patients treated by intravitreal triamcinolone (group B). Institutional study carried out by retrospective analysis of patient registers including serial optical coherence tomography (OCT) images at baseline, and after 1 and 4 months. A central macular thickness (CMT) and vitreomacular relationship was noted on OCT. PVD was graded on a linear scale (0–4). Change in grade of PVD was correlated with change in CMT at each follow-up. At month 4, the decrease in mean CMT from baseline was 51.2 μ (P = 0.000) and 45 μ (P = 0.022) in group A and group B, respectively, with no significant difference between the two groups (P = 0.874). A change in grades of PVD from baseline to month 4 was significant in both group A (P = 0.001) and group B (P = 0.004) with no significant difference between the two groups (P = 0.906). A significant correlation between change in PVD and reduction of CMT was observed in group A (P = 0.011) but not in group B (P = 0.315). Both bevacizumab and triamcinolone caused a significant reduction in macular thickness and a significant change in grade of PVD. Change in PVD played an influential role in the reduction of macular thickness following bevacizumab.