Impact of COPD on pulmonary complications and on long-term survival of patients undergoing surgery for NSCLC

PURPOSE: The purpose of our study was to determine the incidence of various types of postoperative pulmonary complications and to evaluate the impact of chronic obstructive pulmonary disease (COPD) on the long-term survival of patients with non-small cell lung cancer (NSCLC) undergoing pulmonary resection. METHODS: We performed a retrospective chart review of 244 patients who had undergone lung resection for NSCLC at Indiana University. COPD, defined as predicted forced expiratory volume in 1 s (FEV1)< or =70% and FEV1/FVC< or =70%, was determined based on preoperative pulmonary function testing in 78 of 244 patients (COPD group). The remaining 166 patients were classified as non-COPD. The incidence of postoperative complications, which included air leak of > or=10 days, atelectasis, pneumothorax, pneumonia, bronchopleural fistula, empyema, acute respiratory distress syndrome, mechanical ventilation of > or =7 days, and outpatient oxygen supplementation were compared between the two groups. Long-term survival and mortality due to respiratory failure were analyzed between the two groups using the Kaplan-Meier method and log rank test. RESULTS: All of the above-stated postoperative pulmonary complications occurred more frequently in the COPD than in the non-COPD patients (all P<0.01). The overall 5-year survival rate was 36.2% in the COPD and 41.2% in the non-COPD patients (P=0.1023). Five-year cancer related survival was 43.2% in the COPD and 47.7% in the non-COPD patients (P=0.357). There was no significant difference in survival among patients with different stages of lung cancer. However, the intercurrent survival, which is associated with non-cancer related death, was 60.1% in patients with COPD and 86.2% in patients without COPD at 5 years (P<0.0001). The major cause of non-cancer related death in the COPD group was respiratory failure (P=0.0008). CONCLUSION: The presence of COPD is an acceptable predictor of postoperative pulmonary complications in patients with NSCLC. COPD is also a significant risk factor for development of respiratory-related complications, which may explain the poor long-term survival in these patients.     

Efficacy of elevated body swing test in the early model of Parkinson's disease in rat

Animal models of Parkinson's disease (PD) with partial damage of the dopaminergic nigrostriatal system are very suitable for the development of neuroprotective and neurotrophic treatment strategies. Although drug-induced rotational behavior has conventionally been used for the analysis of lesioned animals, a pure behavioral test that can evaluate such animals in a drug-free state may better reflect a more natural response following lesion. In this study, an early model of PD was developed by intrastriatal injection of 12.5 microg of 6-hydroxydopamine (6-OHDA) into the left striatum. Apomorphine-induced rotational and drug-free elevated body swing behaviors were evaluated. The results of the rotational test revealed a very significant contralateral turning in the rats of the lesion group (L+V) compared with the sham-operated group (SH) (P<.0001). In addition, the results of elevated body swing test (EBST) showed a significant difference between the L+V and SH groups in the second (P<.01) and fourth weeks (P<.05) after surgery. Further analysis of correlation for the net number of rotations versus the net number of swings revealed a significant and positive correlation (r=.52) in the second week in the L+V group, but no such correlation was observed in the fourth week (r=.24). Taken together, it is concluded that despite a poor correlation at fourth week postlesion, EBST itself may be appropriate and sensitive for the evaluation of motor asymmetry in the unilateral model of early PD in rats.     

Incremental Hemodialysis: The University of California Irvine Experience

Incremental hemodialysis has been examined as a viable hemodialysis regimen for selected end‐stage renal disease (ESRD) patients. Preservation of residual kidney function (RKF) has been the driving impetus for this approach given its benefits upon the survival and quality of life of dialysis patients. While clinical practice guidelines recommend an incremental start of dialysis in peritoneal dialysis patients with substantial RKF, there remains little guidance with respect to incremental hemodialysis as an initial renal replacement therapy regimen. Indeed, several large population‐based studies suggest that incremental twice‐weekly vs. conventional thrice‐weekly hemodialysis has favorable impact upon RKF trajectory and survival among patients with adequate renal urea clearance and/or urine output. In this report, we describe a case series of 13 ambulatory incident ESRD patients enrolled in a university‐based center's Incremental Hemodialysis Program over the period of January 2015 to August 2016 and followed through December 2016. Among five patients who maintained a twice‐weekly hemodialysis schedule vs. eight patients who transitioned to thrice‐weekly hemodialysis, we describe and compare patients’ longitudinal case‐mix, laboratory, and dialysis treatment characteristics over time. The University of California Irvine Experience is the first systemically examined twice‐weekly hemodialysis practice in North America. While future studies are needed to refine the optimal approaches and the ideal patient population for implementation of incremental hemodialysis, our case‐series serves as a first report of this innovative management strategy among incident ESRD patients with substantial RKF, and a template for implementation of this regimen.     

Automatic CT-SPECT registration of livers treated with radioactive microspheres

We have developed an automated technique to accurately register the CT and SPECT scans of the liver of patients treated with radioactive microspheres for tumour targeting assessment. An anthropomorphic phantom was used to validate the accuracy of the registration algorithm. The phantom liver and three fiducial markers placed on its surface were filled with 99mTc. The phantom was scanned with CT and SPECT scanners in different positions. The liver volume was contoured on the CT scans from which a three-dimensional liver mask was created. By constraining the liver volume to the volume obtained from the CT scans, another liver mask was automatically created from the SPECT images. An adaptive simulated annealing algorithm was used to minimize the difference between the two volumes formed by the two sets of masks. The algorithm involved rigid transformation of the SPECT mask to reach the optimization goal. The accuracy of the algorithm was evaluated by the superposition of the fiducial markers on the CT and SPECT. The registered SPECT overlaid on the CT scan of the phantom showed congruence of the fiducial markers on CT and SPECT images within 1 mm. The technique was applied to a patient image set who received the microsphere infusion procedure. The registered CT and SPECT images of the patient showed that the majority of the activity was concentrated in the tumour, indicating a successful tumour targeting.     

An Accurate Confirmation of Human Immunodeficiency Virus Type 1 (HIV-1) and 2 (HIV-2) Infections with a Dot blot assay Using Recombinant p24, gp41, gp120 and gp36 Antigens

An immunoblot assay using four recombinant proteins corresponding to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) gene products was developed to confirm the presence of antibodies to HIV-1 and 2 in sera reactive in screening ELISAs. Serum samples for testing were obtained from healthy seronegative blood donors and from different categories of HIV-infected individuals (asymptomatic HIV-infected, and AIDS). A positive reaction was defined as reactivity against gag (p24) and at least one other env (either gp41 or gp120) HIV gene products; negative result was defined as no reaction with any antigen; and indeterminate result was defined as reactivity with gag (p24) or with env (gp41 or gp120) alone. None of the 180 serum samples from healthy seronegative blood donors gave a positive result, and only 4 of these samples (2.2%) gave indeterminate results. The recombinant HIV Dot blotting assay identified seropositive individuals with a high degree of accuracy; none of the 125 HIV-seropositive subjects had a negative test result. Reactivity with these antigens, demonstrated 100% sensitivity and specificity in distinguishing seronegative from seropositive sera. All seronegative and seropositive samples were tested both with the commercially available ELISA and by Western blot. The recombinant in-house HIV Dot blot assay accurately identified more seropositive and seronegative samples and had fewer indeterminate results than did commercial Western blot (as interpreted by CDC criteria).     

Activation of human mast cells through stem cell factor receptor (KIT) is associated with expression of bcl-2

BACKGROUND: Mast cells (MCs) are multifunctional effector cells of the immune system. These cells originate from pluripotent hemopoietic progenitors. In contrast to basophils and other leukocytes, MCs exhibit a remarkably long life span (years) in vivo. Although a role for stem cell factor (SCF) and SCF receptor (KIT) in long-term survival of MCs has been proposed, the underlying biochemical mechanisms remain unknown. MATERIALS AND METHODS: We have examined expression of 'survival-related' molecules of the bcl-2 family including bcl-2 and bcl-x(L), in primary human MCs and the human MC line HMC-1. Primary MCs were isolated from dispersed lung tissue by cell sorting using an antibody against KIT. mRNA expression was analyzed by RT-PCR and Northern blotting. Results: As assessed by RT-PCR, purified unstimulated lung MCs (>98% pure) exhibited KIT- and bcl-x(L) mRNA, but did not express bcl-2 mRNA. However, exposure of lung MCS to SCF (100 ng/ml) for 8 h resulted in expression of bcl-2 mRNA. Corresponding results were obtained by immunocytochemistry. In fact, exposure of MC to SCF resulted in expression of the bcl-2 protein whereas unstimulated MCs displayed only the bcl-x(L) protein without expressing the bcl-2 protein. The human MC leukemia cell line HMC-1, which contains a mutated and intrinsically activated SCF receptor, showed constitutive expression of both bcl-2 and bcl-x(L) at the mRNA and protein level. CONCLUSION: Our data show that human MCs can express members of the bcl-2 family. It is hypothesized that bcl-x(L) plays a role in KIT-independent growth of MCs, whereas bcl-2 may be involved in KIT-dependent functions of MCs.     

Dielectric and viscometric behaviour of poly(dibenzyl itaconate) as a function of temperature

The dielectric and viscometric behaviour of poly(dibenzyl itaconate) ( 1 ) in 1,4-dioxane is studied as a function of temperature. The dipole moments at 25°C and at 33°C are determined by measuring the dielectric constant as a function of polymer concentration at fixed temperature. Also, the variation of the dielectric constant for a fixed concentration is determined at several temperatures in the temperature range between 15 and 39°C. The dipole moment is by 10% higher at 33°C than at 25°C, and the variation of the dielectric constant with temperature shows a stepwise increase between 25°C and 30°C. Viscosity measurements demonstrate an anomalous behaviour of 1 in 1, 4-dioxane at approximately the same range of temperatures. At ca. 25°C the value of the Huggins constant drops to practically zero. By measuring samples with different molecular weights the unperturbed dimensions, interaction parameter, and Mark-Houwink-Kuhn-Sakurada exponent are obtained. All of these parameters exhibit a discontinuity at ca. 25°C. The variations in the dielectric and viscometric behaviour with temperature are attributed to a conformational change of the macromolecules of 1 in 1, 4-dioxane.     

Transthoracic needle biopsy in the diagnosis of large-cell neuroendocrine carcinoma of the lung

To determine the effect of cytological diagnosis, fine-needle aspiration and brush cytology on lung tumors and core-needle biopsy, we retrospectively reviewed 11 cases of large-cell neuroendocrine carcinoma (LCNEC) found in our archives between the years 1997 and 2004. The preoperative cytological diagnosis of LCNEC is challenging because of the broad histologic similarity to other neuroendocrine tumors of the lung. The original cytologic diagnosis was LCNEC in nine of the cases while the remaining two were misdiagnosed as small-cell lung carcinoma. Smears were composed of clusters of intermediate-size cells with amphophylic cytoplasm, some with large nuclei and prominent nucleoli. In two of the cases there was discordance between the cytological findings and the immunohistochemical results. The cytological findings were correlated with histopathological observations.