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Biomedical subjects

R Aris

Publications and source records attributed to R Aris.

At least 19 recordsLinked to original sources
PubMed2006

Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial.

Everolimus is a proliferation signal inhibitor with immunosuppressive activity that may reduce the rate of progression of chronic rejection, bronchiolitis obliterans syndrome (BOS), after lung transplantation. In a randomized, double-blind clinical trial, 213 BOS-free maintenance patients received everolimus (3 mg/day) or azathioprine (AZA, 1-3 mg/kg/day) in combination with cyclosporine and corticosteroids. The prospectively defined primary endpoint was the incidence of efficacy failure (decline in FEV1 >15%[deltaFEV1 >15%], graft loss, death or loss to follow-up) at 12 months. Incidence of efficacy failure at 12 months was significantly lower in the everolimus group than AZA (21.8% vs. 33.9%; p = 0.046); at 24 months, rates of efficacy failure became similar between the groups. At 12 months, the everolimus group had significantly reduced incidences of deltaFEV1 >15%, deltaFEV1 >15% with BOS, and acute rejection. At 24 months, only incidence of acute rejection remained significantly less in the everolimus group. Treatment discontinuations (particularly due to adverse events), serious adverse events and high serum creatinine values were more common with everolimus. For the first time, a drug has demonstrated significant slowing of loss in lung function, suggesting that patients kept on prolonged maintenance treatment with everolimus may benefit from replacing AZA with everolimus 3 months after lung transplantation.

Adrenal Cortex Hormones↗
PubMed2002

Long term results of lung transplantation for cystic fibrosis.

OBJECTIVES: We reviewed our experience with lung transplant for cystic fibrosis (CF) over a 10-year period to identify factors influencing long-term survival. METHODS: One hundred and twenty-three patients with CF have undergone 131 lung transplant procedures at our institution; 114 have had bilateral sequential lung transplants (DLTX) and nine have had bilateral lower lobe transplants from living donors. Three patients had retransplant for acute graft failure, and five had late retransplant for bronchiolitis obliterans syndrome (BOS). Kaplan-Meier survival was calculated for the entire cohort and for subsets at higher risk of death to determine factors predicting a better outcome. RESULTS: Actuarial survival for the entire group of DLTX CF patients was 81% at 1 year, 59% at 5 years, and 38% at 10 years. Lobar transplant was associated with a poorer survival (37.5% at 1 and 5 years). Among DLTX patients, colonization with Burkholderia cepacia was present in 22 patients and was associated with poorer outcome (1- and 5-year survival 60 and 36% in B. cepacia patients vs. 86 and 64% in non-cepacia patients). DLTX patients younger than age 20 (n=22) had a similar survival to patients age 20 or older (n=90). Being on a ventilator at the time of transplant was not associated with poorer survival (n=8). BOS affects increasing numbers of survivors with time. Five CF patients have been retransplanted due to BOS with one operative death and 1-year survival of 60%. CONCLUSIONS: DLTX has acceptable long term survival in CF adults and children with end stage disease. CF patients colonized with B. cepacia have a worse outcome but transplantation is still warranted.

Adolescent↗
PubMed2000

Outpatient care of the cystic fibrosis patient after lung transplantation.

Lung transplantation has become an accepted treatment for respiratory failure due to cystic fibrosis (CF). Effective means of patient selection, surgical technique, immunosuppression, and post-transplant management permit survival as good as that of transplant patients with other diseases. The new lungs do not acquire the CF ion transport abnormalities but are subject to the usual post-transplant complications. CF problems in other organ systems persist and may be worsened by some of the immunosuppressive regimens. Prolonged survival increases the risk of age-related CF and other complications. Effective medical management requires expert knowledge of CF and lung transplantation and of how their problems interact, and good communications among the participating care teams.

Antibiotic Prophylaxis↗
PubMed1997

Recurrence of allergic bronchopulmonary aspergillosis in the posttransplant lungs of a cystic fibrosis patient.

Cystic fibrosis (CF) is an autosomal recessive disease of exocrine origin. Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic disorder caused by colonization of the airways with Aspergillus fumigatus. A fumigatus has been cultured from posttransplant lungs in CF patients. Colonization of posttransplant lung with Aspergillus is a recognized phenomenon. In this case report, however, we present a patient who developed ABPA both before and after lung transplant. This patient meets the criteria for ABPA based on serologic results. ABPA may be a complication in post-CF lung transplant patients and serologic analysis should be considered when eosinophilia and pulmonary infiltrates or decline in lung function occurs.

Adult↗
PubMed1996

Acute and chronic lung allograft rejection during pregnancy.

Young women who undergo lung transplantation may regain normal fertility and become pregnant. Currently, little is known about the outcome of pregnancy after lung transplantation. We present a case of pregnancy after bilateral lung transplantation complicated by acute and chronic allograft rejection, resulting in irreversible loss of lung function.

Abortion, Therapeutic↗
PubMed1994

Lung epithelial lining fluid T cell subsets defined by distinct patterns of beta 7 and beta 1 integrin expression.

Integrins are heterodimeric cell-surface glycoproteins that mediate cell-cell and cell-matrix adhesion. We previously identified cDNA encoding a novel integrin beta subunit, beta 7, from bronchoalveolar lavage fluid (BALF) leukocytes. The beta 7 subunit protein is now known to associate with at least two integrin alpha subunits on lymphocytes. One beta 7 integrin, alpha 4 beta 7, mediates lymphocyte adhesion to endothelium and to fibronectin. The other known beta 7 integrin, alpha E beta 7, has recently been shown to mediate lymphocyte-epithelial cell adhesion in vitro. We used flow microfluorometry to analyze the expression of alpha 4 beta 7, alpha E beta 7, and other integrins on blood T cells and epithelial lining fluid T cells obtained from five healthy adult volunteers by bronchoalveolar lavage. alpha 4 beta 7 was the predominant beta 7 integrin on blood T cells, whereas alpha E beta 7 was predominant on BALF T cells. BALF T cells could be divided into alpha E beta 7- and alpha E beta 7+ subsets. Between 29 and 61% (mean 42%) of CD3+ T cells were alpha E beta 7+ alpha E beta 7 was more likely to be present on CD8+ T cells (mean 69% alpha E beta 7+) than on CD4+ T cells (mean 29% alpha E beta 7+). The alpha E beta 7- and alpha E beta 7+ BALF T cell subsets were also found to differ in their expression of other integrins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effects of nitric acid gas alone or in combination with ozone on healthy volunteers.

Nitric acid (HNO3) is the most prevalent acid air pollutant in the western United States and has the potential to cause adverse respiratory effects through both acidification and oxidation reactions. To study this potential, we measured physiologic (specific airway resistance, SRaw, FEV1, and FVC) and bronchoalveolar lavage (total and differential cell counts, LDH, fibronectin, and total protein) end points in a group of 10 healthy, athletic subjects who were exposed to 500 micrograms/m3 of HNO3 gas or filtered air for 4 h during moderate exercise (ventilatory rate, 40 L/min) and underwent bronchoscopy 18 h later. Under an identical protocol, 10 healthy subjects were exposed to 500 micrograms/m3 of HNO3 gas plus 0.20 ppm ozone (O3) or 0.20 ppm O3 alone to determine if HNO3 might enhance the toxicity of O3. In addition to bronchoalveolar lavage (BAL), we employed the techniques of isolated left mainstem bronchial lavage and bronchial biopsy to determine if proximal airway injury was caused by pollutant exposure and whether there was any correlation with the degree of distal lung injury as assessed by BAL. We found no significant differences in pulmonary function tests or in the cellular or biochemical constituents in either the BAL or the left mainstem lavage fluids between the HNO3 and the air exposures. Similarly, there were no differences in these end points between the HNO3/O3 and the O3 exposures. Furthermore, there were no significant differences in the bronchial biopsy specimens between the HNO3 and air exposures or between the HNO3/O3 and O3 exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The effects of sequential exposure to acidic fog and ozone on pulmonary function in exercising subjects.

In Southern California coastal regions, morning fog is often acidified by the presence of nitric acid (HNO3). Peak exposure to ozone (O3) usually occurs in the afternoon and evening, after the fog has dissipated. To determine whether fog containing HNO3 might enhance pulmonary responses to O3, we studied a group of healthy, athletic subjects selected for lung function sensitivity to O3. On 3 separate days, the subjects exercised for 2 h in atmospheres containing HNO3 fog (0.5 mg/ml), H2O fog, or clean, filtered air. After a 1-h break, they exercised for an additional 3 h in an atmosphere containing 0.20 ppm O3. Surprisingly, the mean O3-induced decrements in FEV1 and FVC were smaller after exercise in each fog-containing atmosphere than they were after exercise in clean, filtered air. The mean (+/- SEM) O3-induced decrements in FEV1 were 26.4 +/- 5.3% after air, 17.1 +/- 3.7% after H2O fog, and 18.0 +/- 4.3% after HNO3 fog, and in FVC they were 19.9 +/- 4.7% after air, 13.6 +/- 2.8% after H2O fog, and 13.6 +/- 4.2% after HNO3 fog.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Lack of bronchoconstrictor response to sulfuric acid aerosols and fogs.

Sulfuric acid (H2SO4) is the most common acid air pollutant in the United States and is thought to have adverse respiratory effects. Sulfuric acid exists in polluted air as a dissolved solute in both small (haze) and large (fog) particles. Previous work in our laboratory has failed to demonstrate bronchoconstriction after near ambient, large-particle H2SO4 exposure in subjects with asthma. However, other investigators have found slight but significant changes in lung function following inhalation of small-particle or small-particle, low-relative-humidity (RH) H2SO4 aerosols, leading us to hypothesize that particle size and/or RH may be important variables in acid aerosol exposure. We initially studied the effects of resting inhalation of large-particle (volume median diameter, VMD, approximately equal to 6 microns) and small-particle (VMD approximately equal to 0.4 microns) aerosols with an H2SO4 concentration of 3 mg/m3 through a mouthpiece and found no effect on specific airway resistance (SRaw) or symptom scores. In a second mouthpiece study designed to compare high-RH (100%), large-particle (VMD approximately equal to 6 microns) and low-RH (less than 10%), small-particle (VMD approximately equal to 0.3 microns) aerosols with an H2SO4 concentration of 3 mg/m3, we again found no effect of either aerosol. We then examined the effects of small-particle aerosols inhaled in dry air during moderate exercise. Although breathing low-RH air during exercise provoked increases in SRaw in almost all subjects, this could not be attributed to H2SO4 since low-RH saline aerosol produced a similar result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Acid fog-induced bronchoconstriction. The role of hydroxymethanesulfonic acid.

Hydroxymethanesulfonate (HMSA), the bisulfite (HSO3-) adduct of formaldehyde (CH2O), is a common constituent of California acid fogs. HMSA, most stable in a fog pH range of 3 to 5, dissociates at 6.6, the pH of the fluid lining human airways. The dissociation of inhaled HMSA should theoretically generate sulfur dioxide and CH2O, both of which have bronchoconstrictor potential. Thus, we hypothesized that HMSA may have a specific bronchoconstrictor effect independent of its strength as an acid. To determine whether HMSA has such an effect, 19 subjects with mild to moderate asthma were studied using two different protocols. Initially, a mouthpiece study was performed in which 9 subjects, on 2 separate days, inhaled five aerosols containing either sequentially increasing concentrations (0, 30, 100, 300, and 1000 microM) of HMSA in 50 microM sulfuric acid (H2SO4) or 50 microM H2SO4 alone. The subjects inhaled each aerosol for 3 min during tidal breathing at rest. Specific airway resistance (SRaw) was measured before and after each 3-min exposure. There were no significant differences in the mean changes in SRaw among the various aerosol exposures. To confirm this lack of bronchoconstrictor effect of HMSA, we then performed a chamber study in which 10 freely breathing, intermittently exercising subjects were exposed to fog containing either 1 mM HMSA in 5 mM H2SO4 or 5 mM H2SO4 alone for 1 h. SRaw was measured before, during, and at the end of the 1-h exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1982

Effects of cell motility and chemotaxis on microbial population growth.

A mathematical model is developed to elucidate the effects of biophysical transport processes (nutrient diffusion, cell motility, and chemotaxis) along with biochemical reaction processes (cell growth and death, nutrient uptake) upon steady-state bacterial population growth in a finite one-dimensional region. The particular situation considered is that of growth limitation by a nutrient diffusing from an adjacent phase not accessible to the bacteria. It is demonstrated that the cell motility and chemotaxis properties can have great influence on steady-state population size. In fact, motility effects can be as significant as growth kinetic effects, in a manner analogous to diffusion- and reaction-limited regimes in chemically reacting systems. In particular, the following conclusions can be drawn from our analysis for bacterial populations growing at steady-state in a confined, unmixed region: (a) Random motility may lead to decreased population density; (b) chemotaxis can allow increased population density if the chemotactic response is large enough; (c) a species with superior motility properties can outgrow a species with superior growth kinetic properties; (d) motility effects become greater as the size of the confined growth region increases; and (e) motility effects are diminished by significant mass-transfer limitation of the nutrient from the adjacent source phase. The relationships of these results for populations to previous conclusions for individual cells is discussed, and implications for microbial competition are suggested.

Bacterial Physiological Phenomena↗
PubMed1972

Asymmetries generated by diffusion and reaction, and their bearing on active transport through membranes.

A model is presented that suggests that a natural, stable asymmetry may arise on either side of a membrane, even when the bulk conditions on either side of the membrane are the same and the two faces of the membrane are indistinguishable. Equations are derived on the assumption of Michaelis-Menten kinetics with substrate inhibition to describe the properties of such a model membrane.

Biological Transport, Active↗