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Biomedical subjects

A A Floreani

Publications and source records attributed to A A Floreani.

18 recordsLinked to original sources
PubMed1999

The role of cigarette smoke in the pathogenesis of asthma and as a trigger for acute symptoms.

Although it has been long believed that cigarette smoke is injurious to the lower respiratory tract, the exact early mechanisms and early events responsible for this injury remain unclear. Maternal smoking, particularly in utero, is clearly associated with an increased risk for the later development of childhood atopy and asthma. Smoking is known to increase the inflammatory burden of the lower respiratory tract through a number of related but separate mechanisms. These include the recruitment of increased numbers of inflammatory cells, alteration in cell subtypes, enhancement of some cellular functions, and proinflammatory mediator release. In addition, cigarette smoking in vitro and in animal models appears to promote neurogenic inflammation, increase oxidative stress and lead to the elevation of cysteinyl leukotrienes, all of which could potentially lead to an amplification of the airway inflammation already present in asthmatics. Greater and more consistent effort must be given to encourage the young asthmatic not to smoke. In addition, greater effort must be spent on smoking cessation, especially in pregnant women and young asthmatics.

Adult↗
PubMed1999

Protein kinase C activation is required for cigarette smoke-enhanced C5a-mediated release of interleukin-8 in human bronchial epithelial cells.

Complement-derived anaphylatoxin C5a is a glycopolypeptide important in the regulation of inflammation. Previously, we have shown that C5a receptors (C5aR) are constitutively expressed on human bronchial epithelial cells (HBECs) grown in culture. We have also shown that the expression of C5aR is increased upon exposure of HBECs to 5% cigarette smoke extract (CSE), and that this subtoxic dose of CSE significantly enhances C5a-stimulated interleukin (IL)-8 release. To determine the intracellular signaling pathway of CSE + C5a-mediated IL-8 release, we assayed protein kinase C (PKC) activity of HBECs after exposing the cells to CSE and/or C5a. No increase in PKC activity was observed when HBECs were treated with 50 nM C5a for various times. However, PKC activity was increased by 2- to 3-fold in HBECs stimulated with 5% CSE for 1 h, as compared with cells incubated with medium only. No additional increase in PKC was observed when HBECs were treated with CSE and C5a together. When HBECs were pretreated with the PKC-specific inhibitor calphostin C (1 microM), no CSE-mediated PKC activation was observed. We then correlated PKC activation with IL-8 release in the same cells. Although HBECs required stimulation by both CSE and C5a to release maximal levels of IL-8, preincubation of CSE-stimulated HBECs with calphostin C inhibited IL-8 release by CSE + C5a. These results suggest that PKC activation by CSE alone does not result in IL-8 release, but that CSE-stimulated PKC activation is required for C5a-mediated IL-8 release from HBECs.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Thoracic complications related to bone marrow transplantation.

Although progress has been made in the diagnosis and management of respiratory complications after BMT, such complications are still frequent and are a major cause of morbidity and mortality. The use of CMV-negative marrow and blood products, surveillance bronchoscopies, and prophylactic use of antivirals have significantly reduced the incidence of CMV pneumonia. DNA amplification techniques have allowed earlier detection of viral respiratory infections, and early detection of localized invasive aspergillosis can improve survival with lung resection and antifungal therapy. Finally, consideration for open lung biopsy should include the patient's degree of preoperative respiratory impairment, because this may relate to early postoperative survival.

Bone Marrow Transplantation↗
PubMed1998

Expression of receptors for C5a anaphylatoxin (CD88) on human bronchial epithelial cells: enhancement of C5a-mediated release of IL-8 upon exposure to cigarette smoke.

Results are presented that demonstrate a heightened responsiveness of human bronchial epithelial cells (HBECs) toward the complement-derived anaphylatoxin C5a when these cells are exposed to cigarette smoke. This C5a response is possible because we show at both the protein and mRNA levels that HBECs constitutively express receptors for C5a (C5aR, CD88). Control (untreated) HBECs responded to C5a (50 nM) by releasing the proinflammatory cytokine IL-8 at low but significant levels. However, exposure of HBECs to 5% cigarette smoke extract (CSE) for at least 15 min resulted in an increase in the ability of an anti-human C5aR Ab to bind to the cell surface. CSE-treated HBECs responded in a dose-dependent fashion to human recombinant C5a and to a conformationally biased decapeptide agonist of C5a (YSFKPMPLaR) by releasing IL-8. The levels of IL-8 released in response to C5a were significantly greater in CSE-treated HBECs than in control HBECs. Moreover, this C5a-mediated release of IL-8 from CSE-treated HBECs was significantly reduced in the presence of the anti-human C5aR Ab. These results indicate that HBECs constitutively express C5aRs and that exposure to environmental irritants such as cigarette smoke modulates the expression and responsiveness of these C5aRs toward the C5a-mediated release of IL-8.

Adult↗
PubMed1997

Experimental treatments for asthma.

There has been increased recognition of the importance of inflammatory cells and their products in the pathogenesis of asthma. From this recognition has evolved a number of new approaches to treat the various components of the asthmatic inflammatory response. Nonselective anti-inflammatory agents such as cyclosporine and gold appear to decrease symptoms and allow a steroid-sparing effect in many cases, though side effects from cyclosporine often necessitate dose reduction. Novel oral compounds as the 5-lipoxygenase inhibitors have been effective in controlling asthma symptoms triggered by various stimuli, and the cysteinyl leukotriene receptor antagonists have shown promise in this regard as well. Neurokinin antagonists, inhaled loop diuretics, and lidocaine may play significant roles in asthma therapy through inhibition of neurogenic inflammation and possibly mast cell function. Inhibition of mast cell products by existing drugs such as heparin or the development of specific inhibitors of mast cell tryptase may also be effective agents, as are selective phosphodiesterase inhibitors, which appear to have anti-inflammatory properties. Finally, specific cytokine antagonists, agonists, inhibitors of T-cell function, selective inducible nitric oxide synthase inhibitors, and even gene-directed strategies may provide not only insights into the pathogenesis of asthma but also novel therapeutic approaches to treat the inflammation in this disease.

Administration, Inhalation↗
PubMed1996

Measurement of exhaled nitric oxide by three different techniques.

The purpose of the study was to compare exhaled nitric oxide (NO) determined by three techniques. Ninety-one subjects performed a slow vital capacity maneuver: (1) through the mouth directly into a NO chemiluminescence analyzer (peak oral NO), (2) through the mouth into a collection bag (mean oral NO), and (3) through the nose into a collection bag (mean nasal NO). Peak oral NO was higher in patients with asthma (n = 18, 174.2 +/- 27.0 ppb), but lower in smokers (n = 36, 39.6 +/- 4.8 ppb) compared with nonsmoking control subjects (n = 23, 105.5 +/- 8.4 ppb, p < 0.05 both comparisons). Mean oral NO levels were significantly lower than peak oral NO levels (p < 0.05), but still higher in patients with asthma in comparison with nonsmoking healthy control subjects and asymptomatic smokers (27.2 +/- 3.5 versus 14.5 +/- 1.1 and 7.3 +/- 0.7 ppb, respectively, p < 0.05). In contrast, there was no significant difference in mean nasal NO levels between the three groups. Peak oral NO and mean oral NO levels correlated (r = 0.772, p < 0.0001). Determination of exhaled oral NO levels is qualitatively independent of the technique used, but nasal exhalation may affect NO determination in conditions associated with airway inflammation.

Adult↗
PubMed1996

Cardiopulmonary function and autologous bone marrow transplantation: results and predictive value for respiratory failure and mortality. The University of Nebraska Medical Center Bone Marrow Transplantation Pulmonary Study Group.

Cardiopulmonary complications are a major cause of morbidity and mortality in patients undergoing high-dose therapy with stem cell transplant support. Since exercise tolerance testing (ETT) assesses the cardiopulmonary reserve of an individual, we hypothesized that ETT performed prior to transplant would predict respiratory failure and mortality and would be a superior predictor over resting cardiopulmonary function tests. We performed a retrospective study of 191 lymphoma patients who underwent ETT prior to transplant between 1 June 1990 and 31 December 1992 and compared the results of ETT with resting pulmonary function tests (PFT) and resting cardiac ejection fraction (EF). ETT revealed that cardiac, pulmonary and combined cardiopulmonary limitation were observed in 31, 20 and 16% of the patients, respectively, with a gas diffusion-type limitation being the most common exercise limitation. Resting PFT were abnormal in 58% of patients with a diffusion defect being the most common abnormality. Low EF was observed in 6.8% of patients. Twelve patients eventually required mechanical ventilation post-transplant with only the resting diffusion PFT predictive of this complication. There were five early deaths that were attributable to respiratory failure and neither resting nor ETT studies were predictive of these deaths. ETT and EF performed prior to transplant in lymphoma patients undergoing autologous transplant do not predict for either respiratory failure or short-term mortality. Our findings may be due to the rather low incidence of respiratory failure (6.3%) and low early mortality from cardiopulmonary complications (2.6%) seen in our patient population.

Adolescent↗
PubMed1995

Combined occurrence of chyloperitoneum and chylothorax after retroperitoneal surgery.

Chyloperitoneum is a rare complication of abdominal or retroperitoneal surgery, and the combined occurrence of chylothorax and chyloperitoneum has been reported in only a few cases. We describe a case of this complication, which became clinically apparent 20 days after a Warren shunt operation. The large chylous effusion compromised breathing and required chest tube drainage, pleurodesis, medium chain triglyceride (MCT) diet, and, later, total parenteral nutrition (TPN). The patient made a full recovery on TPN for 5 weeks.

Adult↗
PubMed1995

Nonstandard and potential future therapies for asthma.

This article provides a broad outline of selected areas that offer promise for novel therapy in asthma. Special attention is given to pharmacologic approaches to asthma and to the kinds of investigation that are required to establish these therapies, recognizing that their development may require approaches different from those used for the development of drugs designed to symptomatically treat asthma.

Asthma↗
PubMed1994

Smoking reduction: an alternative approach for smokers who cannot quit.

Cigarette smoking is the foremost cause of death in the United States and is a major health problem worldwide. Clearly, the best way to eliminate the risk of smoking-related diseases, is to quit smoking. Smoking cessation has immediate and long-term benefits and substantially reduces the risk of many smoking-related diseases. Unfortunately, quitting smoking is rarely easy. For those smokers who cannot or do not wish to quit, reduction in their total smoking may represent a potential health benefit. Reduction in total smoking can, theoretically, be achieved by: 1) reducing the number of cigarettes smoked daily; and/or 2) switching to a low tar/low nicotine cigarette. Smokers, however, tend to self-adjust nicotine to maintain relatively constant levels. Reduction in tar/nicotine content or number of cigarettes, therefore, may not produce health benefits. Smoking reduction with alternative nicotine delivery, however, may represent an alternative option for smokers who cannot, or do not, wish to quit.

Humans↗
PubMed1994

In vivo assessment of airway inflammation.

Chronic obstructive pulmonary disease (COPD) and asthma are chronic inflammatory diseases which cause considerable morbidity and mortality. A number of in vivo methods have been developed to assess airway inflammation both to study mechanistic factors leading to airway inflammation as well as to assess disease activity. These have included non-invasive tests such as pulmonary function testing, bronchial provacation testing and nuclear medicine scans. Bronchoalveolar lavage and bronchoscopic derived biopsies of the airways have provided information regarding cell populations and inflammatory mediators involved in the pathogenesis of chronic airway and lung inflammation. Induced sputum may become a less invasive means to sample the lower respiratory tract in patients with these disorders.

Asthma↗
PubMed1993

Bovine bronchial epithelial cells metabolize L-arginine to L-citrulline: possible role of nitric oxide synthase.

The conversion of L-arginine to L-citrulline is catalyzed by nitric oxide synthase (NOS), and results in the release of nitric oxide (NO). We hypothesized that bronchial epithelial cells metabolize L-arginine to L-citrulline. We found that cell lysates obtained from unstimulated, cultured bovine bronchial epithelial cells (BBECs) converted L-[3H]arginine to L-[3H]citrulline. This conversion was attenuated by three competitive NOS inhibitors and modulated by lipopolysaccharide and cigarette smoke extract (p < 0.01, all comparisons). These data demonstrate that BBECs metabolize L-arginine to L-citrulline and implicate a role for the L-arginine:NOS biosynthetic pathway in modulating airway responses.

Amino Acid Oxidoreductases↗
PubMed1993

General vs local anesthesia. Effect on bronchoalveolar lavage findings.

Bronchoalveolar lavage (BAL) can be performed with the patient undergoing either local or general anesthesia (GA). This study investigates whether the type of anesthesia affects BAL fluid and cell recovery. Eighty patients, were selected for study. Fluid recoveries were significantly less in the GA group for both the bronchial and alveolar lavages. The differences were confirmed for BAL fluid recovery in a subsequent group of 120 unselected patients. Bronchoscope size did not appear to affect recovery, nor did anesthesia time; BAL fluid recovery from patients with respiratory failure who were intubated and mechanically ventilated was similar to that in the GA group, suggesting that lower recovery rates may be due to mechanical ventilation. The BAL fluid cell counts were related to fluid recovery, but airway neutrophils represented a higher percentage of BAL lavage fluid cells in the GA lavages, independent of differences in the volume of lavage fluid recovered.

Adult↗
PubMed1992

Pulmonary complications of transplantation.

Improved immunosuppressive regimens, advances in surgical proficiency and techniques, and improved supportive medical care have translated into dramatic increases in graft survival in organ transplantation and in patient outcome in bone marrow transplantation. Though effective immunosuppression has also led to an increase in infectious complications, several recent advances, including the development of effective surveillance protocols and antiviral therapy and the use of prophylactic antibiotics, appear to have made a significant positive impact on the management of infections and survival of transplant recipients. In addition, a clearer understanding of noninfectious pulmonary complications, such as bronchiolitis obliterans, and continued improvement in techniques for evaluating a host of posttransplant pulmonary disorders will likely further enhance posttransplant therapy and survival.

Bronchiolitis Obliterans↗
PubMed1989

Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury.

The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

Animals↗