Assessment of bronchial obstruction and its reversibility by shape indexes of the flow‐volume loop in asthmatic children

Asthma assessment by spirometry is challenging in children as forced expiratory volume in 1 s (FEV1) is frequently normal at baseline. Bronchodilator (BD) reversibility testing may reinforce asthma diagnosis but FEV1 sensitivity in children is controversial. Ventilation inhomogeneity, an early sign of airway obstruction, is described by the upward concavity of the descending limb of the forced expiratory flow‐volume loop (FVL), not detected by FEV1. The aim was to test the sensitivity and specificity of FVL shape indexes as β‐angle and forced expiratory flow at 50% of the forced vital capacity (FEF50)/peak expiratory flow (PEF) ratio, to identify asthmatics from healthy children in comparison to “usual” spirometric parameters. Seventy‐two school‐aged asthmatic children and 29 controls were prospectively included. Children performed forced spirometry at baseline and after BD inhalation. Parameters were expressed at baseline as z‐scores and BD reversibility as percentage of change reported to baseline value (Δ%). Receiver operating characteristic curves were generated and sensitivity and specificity at respective thresholds reported. Asthmatics presented significantly smaller zβ‐angle, zFEF50/PEF and zFEV1 (p ≤ .04) and higher BD reversibility, significant for Δ%FEF50/PEF (p = .02) with no difference for Δ%FEV1. zβ‐angle and zFEF50/PEF exhibited better sensitivity (0.58, respectively 0.60) than zFEV1 (0.50), and similar specificity (0.72). Δ%β‐angle showed higher sensitivity compared to Δ%FEV1 (0.72 vs. 0.42), but low specificity (0.52 vs. 0.86). Quantitative and qualitative assessment of FVL by adding shape indexes to spirometry interpretation may improve the ability to detect an airway obstruction, FEV1 reflecting more proximal while shape indexes peripheral bronchial obstruction.     

Addition of etoposide to cyclophosphamide, doxorubicin, and vincristine for remission induction and survival in patients with small cell lung cancer

A total of 116 patients with small cell lung cancer were randomized to receive either: cyclophosphamide, 750 mg/m2, doxorubicin, 50 mg/m2, and vincristine, 2 mg iv (Regimen A), or the same drugs plus etoposide, 100 mg/m2 iv daily for 2 days (Regimen B) every 3 weeks. Complete responders received whole-brain radiation therapy. The overall response rates were 50% for Regimen A and 65% for Regimen B (P less than 0.05). The complete response rates were 18% for Regimen A and 44% for Regimen B (P less than 0.01). For patients with limited disease, the complete responders were 35% on Regimen A and 52% on Regimen B (P = 0.26); for those with extensive disease, the complete responders were 0% on Regimen A and 35% on Regimen B (P = 0.002). The median survival for complete responders was 17 months on Regimen A and 20 months on Regimen B. The difference is not statistically significant. Toxicity was tolerable for both groups; however, it was greater for the etoposide arm. We conclude that although etoposide improves the overall response rates in patients with small cell lung cancer, especially those with extensive disease, the addition of this drug does not lead to improved survival.     

Dead cells in melanoma tumors provide abundant antigen for targeted delivery of ionizing radiation by a mAb to melanin

Melanoma is a cancer with a rising incidence, and metastatic disease is almost always lethal. We investigated the feasibility of targeting melanin, an intracellular melanocyte pigment, to deliver cytotoxic radiation to human melanoma cells in vivo by using a melanin-binding mAb (6D2). Nude mice bearing MNT1 pigmented human melanoma tumors were treated with mAb 6D2 labeled with 1.5 mCi (1 Ci = 37 GBq) of the beta-emitter 188-Rhenium (188Re) and manifested inhibition of tumor growth and prolonged survival. mAb 6D2 bound tumor melanin and demonstrated no crossreactivity with normal melanized tissues in black mice. The mechanism of melanin targeting involved Ab binding to extracellular melanin released during tumor cell turnover or to dying cells with permeable membranes. In this approach, the cytotoxic radiation emanating from labeled Ab bound to melanin is presumably delivered by "crossfire" effect to the adjacent viable tumor cells. Our results establish the feasibility of targeting melanin released from dead melanoma cells in tumors with radiolabeled Abs to achieve a therapeutic effect. In contrast to conventional tumor antigens, melanin is insoluble, resistant to degradation, and can be expected to accumulate in targeted tissues, suggesting that the efficacy of therapy could increase with each subsequent treatment cycle.     

Hospital-acquired conditions after bariatric surgery: we can predict,but can we prevent?

Background

Centers for Medicare and Medicaid Services initiated a non-payment policy for certain hospital-acquired conditions (HACs) in 2008. This study aimed to determine the rate of the three most common HACs (surgical site infection (SSI), urinary tract infection (UTI), and venous thromboembolism (VTE)) among bariatric surgery patients. Additionally, the association of HACs with patient factors and the effect of HACs on post-operative outcomes were investigated.

Methods

Patients over 18 years with a body mass index (BMI) ≥35 who underwent bariatric surgery were identified using the American College of Surgeons’ National Surgical Quality Improvement Program (ACS-NSQIP) database (2005–2012). Patients were grouped into two categories: HAC versus no HAC patients and baseline characteristics and outcomes, including 30-day mortality, reoperation, and mean length of stay (LOS) were compared. Multivariable logistic regression analysis was performed to identify the risk factors for developing a HAC.

Results

98,553 patients were identified, 2,809 (2.9 %) developed at least one HACs. SSI was the most common HAC (1.8 %), followed by UTI (0.7 %) and VTE (0.4 %). The rate of these HACs significantly decreased from 4.6 % in 2005–2006 to 2.5 % in 2012 (p < 0.001). Laparoscopic gastric banding was associated with the lowest rates of HAC (1.3 %) and open gastric bypass with the highest (8.0 %). HAC patients had significantly higher rates of in-hospital mortality (0.8 vs. 0.1 %, p < 0.001) and LOS (3.9 vs. 2.1 days, p < 0.001). On adjusted analysis, open GBP patients had 5.36-fold higher odds of developing a HAC. Interestingly, the presence of a resident surgeon 7–11 years post graduation was associated with significantly increased odds of HACs (1.86, 1.50–2.31, p < 0.001).

Conclusion

Our data demonstrate a strong correlation between these three HACs following bariatric surgery and factors intrinsic to the bariatric patient population. This calls into question the non-payment policy for inherent patient factors on which they cannot have impact. These findings are important to help inform health care policy decisions regarding access to care for bariatric surgery patients.     

Structure and function of gustatory neurons in the nucleus of the solitary tract: II. Relationships between neuronal morphology and physiology

This study employed intracellular recording and labeling techniques to examine potential relationships between the physiology and morphology of brainstem gustatory neurons. When we considered the neuronal response to the four “prototypic” tastants, we were able to demonstrate a positive correlation between breadth of responsiveness and the number of dendritic branch points. An analysis of the response to eight tastants also revealed an association between dendritic spine density and the breadth of responsiveness, with more narrowly tuned neurons exhibiting more spines. Interestingly, a neuron's “best response” was a relatively poor predictor of neuronal morphology. When we focused on those neurons that responded to only one tastant, however, a number of potentially important relationships became apparent. We found that the cells that only responded to quinine were smaller than the neurons that only responded to NaCl, HCl, or sucrose. The HCl-only neurons, however, were more widespread in the rostrocaudal dimension than the neurons that only responded to NaCl. A number of additional structure-function relationships were identified when we examined the neuronal response to selected tastants. We found that neurons that responded to sucrose but not quinine, as well as neurons that responded to quinine but not sucrose, were more widespread in the mediolateral dimension than neurons that responded to both sucrose and quinine. We also discovered that the neurons that responded to NaCl, but not to NH₄Cl or KCl, were larger than neurons that responded to all three salts. We believe that these results support the hypothesis that there are relationships between the structure and function of gustatory neurons in the nucleus of the solitary tract, with the data highlighting the importance of three themes: 1) the relationship between dendritic specializations and tuning, 2) the relationship between dendritic arbor orientation and response properties, and 3) the potential importance of stimulus-specific neurons. © 1996 Wiley-Liss, Inc.     

Selective localization and regulated release of calcitonin gene-related peptide from dense-core vesicles in engineered PC12 cells

Introduction of the gene for calcitonin into the neuroendocrine PC12 cell line resulted in the expression of the neuronal-specific splice product, calcitonin gene-related peptide (CGRP). Expression of this neuropeptide did not require treatment of the PC12 cells with NGF. By all available criteria, including biochemical, immunological, and morphological analysis, we have determined that the CGRP in stably transfected PC12 cells is sorted selectively into the large, dense-core catecholamine-containing secretory vesicles. Conversely, the CGRP is excluded from the small, synaptophysin-rich vesicles present in the same cells. Stimulation conditions that trigger the release of catecholamines cause a parallel burst in the release of CGRP. In all these respects, the engineered PC12 cells process the foreign CGRP in a manner similar to that seen in spinal motor neurons in vivo. These results indicate that this small (37 amino acids) peptide contains sorting information sufficient for targeting to large, dense-core vesicles in heterologous cells, placing very narrow constraints on the possible location of sorting signals. In addition, this CGRP-expressing cell line opens the possibility of studying the physiological role of CGRP in the establishment and maintenance of neuromuscular contacts. © 1996 Wiley-Liss, Inc.