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Biomedical subjects

T Egan

Publications and source records attributed to T Egan.

At least 19 recordsLinked to original sources

Tobacco and alcohol use in lung transplant candidates and recipients.

Tobacco and alcohol use among lung transplant candidates and recipients is unknown. Our first goal was to describe tobacco and alcohol use before and after lung transplant in patients with cystic fibrosis (CF) and other pulmonary diseases (non-CF). Our second goal was to determine whether demographic variables, depression, anxiety and social support predicted tobacco and alcohol use. Self-report data from transplant candidates and recipients, and transplant nurse coordinator ratings of post-transplant smoking and drinking were utilized. Data from two samples were analyzed. Sample 1 comprised 219 patients being evaluated for lung transplant, and sample 2 comprised 45 transplant recipients who were 1-7 yrs post-transplant. The results from analyzing sample 1 indicated that 72% of non-CF patients and 16% of CF patients had a history of smoking cigarettes, and the majority of patients in both groups had consumed alcohol in the past. For CF patients, past smoking was related to higher depression scores, and past drinking was related to higher education and lower social support. For non-CF patients, a history of smoking was associated with being Caucasian and older. For CF patients, a history of drinking was associated with being older and less depressed, and for non-CF patients a history of drinking was associated with higher education and lower social support. Post-transplant 100% of recipients reported abstinence from tobacco, and over 60% reported abstinence from alcohol. Transplant coordinator ratings corroborated that no transplant recipients were using tobacco products or consuming alcohol in an excessive or problematic manner. For both groups, consuming alcohol after transplant was related to lower levels of social support. In conclusion, lung recipients remain abstinent from tobacco, and although over 30% of patients consume alcohol after transplant, it is not at problematic levels. Smoking and drinking behaviors were related to demographic variables, depression, and low social support.

Adult↗

MALDI matrices for biomolecular analysis based on functionalized carbon nanomaterials.

When used in small molar ratios of matrix to analyte, derivatized fullerenes and single wall nanotubes are shown to be efficient matrices for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The mixing of an acidic functionalized fullerene with a solution of bioanalyte, depositing a dried droplet, and irradiating with a pulsed nitrogen laser yields protonated or cationized molecular ions. Derivatized fullerenes could offer several advantages over conventional MALDI matrices: a high analyte ionization efficiency, a small molar ratios (less than 1) of matrix/analyte, and a broader optical absorption spectrum, which should obviate specific wavelength lasers for MALDI acquisitions. The major disadvantage to the use of fullerenes is the isobaric interference between matrix and analyte ions; however, it is overcome by using MALDI-ion mobility time-of-flight (IM-oTOF) mass spectrometry to preseparate carbon cluster ions from bioanalyte ions prior to TOF mass analysis. However, an alternative to the dried droplet preparation of fullerene MALDI samples is the aerosolization of matrix-analyte solutions (or slurries) followed by impacting the aerosol onto a stainless surface. We also demonstrate that the fullerene matrices can be used to acquire spectra from rat brain tissue.

Amino Acid Sequence↗

Quality of life in patients awaiting lung transplant: cystic fibrosis versus other end-stage lung diseases.

The symptoms associated with chronic lung disease can impair quality of life and psychosocial functioning. The purpose of the present study was to provide a thorough baseline assessment of quality of life in patients with end-stage lung disease and being evaluated for transplant; and to assess potential differences in quality of life between patients with cystic fibrosis (CF) and those with other types of end-stage lung disease (e.g., chronic obstructive pulmonary disease (COPD), interstitial pulmonary fibrosis (IPF)). We evaluated 58 patients with CF and 52 patients with other types of end-stage lung disease who were recruited for this study during an assessment of their candidacy for lung transplant. Subjects completed a battery of questionnaires that assessed demographic factors (including work and educational status), the presence of psychological distress (anxiety and depression), availability of social support, coping styles, and physical functioning. Despite significant impairment in physical functioning in the areas of recreation, household activities, sleep, and ambulation, other indices of life quality suggested good adaptation in the majority of patients. Also, quality of life differed for patients with CF and for those with other types of end-stage lung disease. Patients with CF were more likely to be working, had lower levels of anxiety and higher levels of social support, and used more functional coping strategies than did patients with other end-stage lung disease. These results highlight the fact that patients with different types of lung disease may require different psychosocial services as they await transplant. These findings also raise the question of whether there is a difference in quality of life after transplant between patients with CF and those with other types of lung disease.

Adaptation, Psychological↗

In vivo regulation of von willebrand factor synthesis: von Willebrand factor production in endothelial cells after lung transplantation between normal pigs and von Willebrand factor-deficient pigs.

To evaluate the regulation of plasma von Willebrand factor (vWF) and its in situ production by endothelial cells (ECs), 12 swine leukocyte antigen (SLA)-compatible left lung transplantations were performed. Normal lungs were transplanted into 10 pigs homozygous for von Willebrand disease and into 2 normal pigs. Additionally, 1 normal pig underwent pneumonectomy, and 1 SLA-incompatible lung transplantation between normal pigs was performed. None of the transplanted animals received immunosuppressive therapy. Plasma vWF level was evaluated by ELISA and multimeric pattern. EC vWF content was assessed by immunohistochemistry. Global hemostasis was assessed by standardized ear bleeding time. Six of 12 SLA-compatible lung transplantations and the incompatible transplantation were successful and were used for the study. The functions and the viability of ECs, reflected by their ability to produce vWF and normal multimeric plasma vWF pattern, were preserved in SLA-compatible and -incompatible lung transplantations. vWF production was preserved in ECs that initially synthesized it. EC constitutive and storage pathways are modulated differently according to transplantation compatibility and severity of rejection. In SLA-compatible lung transplantations without histological evidence of rejection, the production of vWF was preserved, whereas constitutive vWF secretion appeared to be altered in cases with minor histological signs of rejection. In pigs with von Willebrand disease that were transplanted with normal lungs without sign of rejection, plasma vWF was significantly increased in an amount expected from the estimated production of a normal lung. In the transplanted normal lung, there was no vWF overexpression by the ECs and no recruitment of ECs that initially did not express vWF. In SLA-incompatible transplantation, ECs were morphologically normal with increased and blurred vWF labeling, whereas plasma vWF levels remained normal, reflecting that EC activation is associated with an increased vWF production with probable diversion to storage pathway. This model depicts the changes of EC regulation of vWF secretion in pig lung transplants. However, this model cannot be directly extrapolated to human organ transplantation because animals did not receive any immunosuppressive therapy, which may be toxic to ECs.

Acute Disease↗

Nucleotide regulation of goblet cells in human airway epithelial explants: normal exocytosis in cystic fibrosis.

The regulation of mucin secretion by airway goblet cells is poorly understood and the receptor-based regulatory mechanisms have not been described in human airways. In the present study, we report that extracellular triphosphate nucleotides regulate the rate of granule release from goblet cells in both normal and cystic fibrosis (CF) airway epithelial explants. Explants isolated from nasal and tracheobronchial tissues were mounted in perfusion chambers and the secretory activity was assessed by videomicroscopic determination of degranulation in single goblet cells and by ELISA determination of mucins secreted into the mucosal perfusate. Baseline degranulation was measured at 0.05 degranulation events (DE)/min. In normal goblet cells, mucosal ATP (10(-4) M, n = 17) induced a biphasic secretory response comprising 29.1 +/- 4.9 DE during the first 5 min, with an initial rate of 118.2 +/- 10.2 DE/min. Mucosal UTP (10(-4) M, n = 9) induced a similar response to ATP (initial rate: 89.2 +/- 23.9 DE/min, 17.9 +/- 5.1 DE in 5 min), but mucosal 2-MeSATP was not an effective agonist (initial rate: 1.5 +/- 1.4 DE/min, 2.3 +/- 0.5 DE in 5 min). Determination of mucins by ELISA confirmed that both ATP and UTP induced similar secretory responses but that 2-MeSATP was not effective. In CF explants, mucosal UTP (10(-4) M, n = 6) induced similar responses to those observed in normal tissues (initial rate: 82.5 +/- 27.5 DE/min, 18.8 +/- 4.1 DE in 5 min). We conclude that human nasal and tracheobronchial goblet cells are stimulated by mucosal nucleotides, probably via a 5'-nucleotide receptor, and that this response is unaffected by CF.

Bronchi↗

Influence of intraalveolar oxygen concentration on lung preservation in a rabbit model.

We previously reported the use of an inexpensive screening model for lung preservation involving ventilation and perfusion of excised rabbit lungs after their preservation. We now have extended this model by perfusing the preserved lung in cross circulation with an anesthetized rabbit to permit stable reperfusion of the preserved lungs for 60 minutes. With this model we compared the results of lung preservation with the lungs inflated with nitrogen, room air, or 100% oxygen during 24 hours of hypothermic storage. Four groups of animals were studied: group 1, excision and immediate evaluation; group 2, inflation with room air and storage for 24 hours at 10 degrees C; group 3, same as group 2, with 100% oxygen for inflation during storage; group 4, same as group 2, with 100% nitrogen for inflation during storage. Assessment of the ex vivo perfused lung consisted of (1) blood gas analysis of inflow and outflow blood at 10-minute intervals; (2) continuous pulmonary artery and airway pressure monitoring; (3) measurement of pulmonary venous oxygen tension after 1 hour of reperfusion, with inflow oxygen tension adjusted to 15 mm Hg; (4) wet/dry weight ratio. We conclude that the paracorporeal circuit does not, in itself, cause lung injury over a 1-hour period; lungs preserved with nitrogen inflation rapidly became edematous and failed to function on reperfusion. Preservation with 100% oxygen inflation appears superior to inflation with room air.

Animals↗

Acute occupational exposure to antineoplastic agents.

Antineoplastic agents may exhibit effects not only in patients therapeutically exposed, but also in health workers who prepare and administer these drugs. Concern to date has focused on long-term health consequences, including adverse reproductive outcomes, altered immunity, and increased cancer risk. The burgeoning use of these drugs for non-malignant illnesses has enlarged the health worker population at risk beyond oncology personnel to include professionals in immunology, rheumatology, nephrology, and dermatology. We report here two cases of hospital workers who experienced acute adverse health effects resulting from occupational exposure to antineoplastic drugs. We believe such acute events are under-reported, and that they demonstrate the need for physician awareness regarding their management.

Adult↗

Determination of ionised calcium by ion selective electrode is not independent of albumin concentration.

The relationship of ionised calcium measurement to changes in serum total protein and albumin were studied both in vivo and in vitro. During venostasis serum ionised calcium was determined in 10 control subjects using an Orion SS20 analyser. A slight but significant increase in ionised calcium occurred only after prolonged venostasis (15 min), when gross changes in total protein and albumin were seen. The effect of albumin concentration on serum ionised calcium was studied in vitro by the dialysis technique of Payne. The increase in ionised calcium in 40 sera was 0.0198 mmol/l per 10 g albumin change. We conclude that albumin-related variation in serum ionised calcium determination required such gross changes that correction is rarely necessary in clinical practice. When gross albumin alteration occurs, the appropriate correction for the analyser used should be determined and applied.

Adult↗

Experimental en bloc double-lung transplantation.

A technique of en bloc double-lung transplantation through a median sternotomy has been developed. Hypothermic circulatory arrest was used after surface cooling in 7 puppies (mean weight, 3.1 kg; range, 1.5 to 4.1 kg). A double lung block, consisting of the two lungs, distal trachea, the main pulmonary artery, and a large cuff of left atrium, was removed from weight-matched donors. After the arrest of the circulation by inflow occlusion, bilateral pneumonectomies were performed in the recipient. The donor double-lung block was then implanted with anastomoses at the distal trachea, the posterior left atrium, and the main pulmonary artery. All animals were successfully rewarmed and had excellent hemodynamic function and gas exchange for periods of up to 24 hours. If primate experiments with long-term survival confirm these initial results, this procedure may have a role in the treatment of patients with end-stage respiratory disease but acceptable cardiac function.

Animals↗

Sleep in Pierre Robin syndrome.

Eight patients (aged 8 to 22 years) with the Pierre Robin syndrome underwent sleep studies. Seven demonstrated significant although minor degrees of increased sleep disturbances and apneas, and less time spent in the rapid-eye-movement (REM) stage of sleep. One patient who had previously undergone mandibular corrective surgery had major sleep abnormalities (central apnea index of 81.7 although an obstructive sleep apnea index of only 1.9). The patients had small mandibles, as demonstrated by lateral cephalometric roentgenography, and mildly increased right ventricular diastolic dimensions, as shown by M-mode echocardiography. Snoring was present in all of these patients and in 13 of 22 patients questioned from our Pierre Robin clinic. We conclude that minor abnormalities in sleep, mandibular size, and right ventricular size persist well into adolescence in the majority of patients with Pierre Robin syndrome. These appear to be clinically insignificant; however, a small percentage of such patients may continue to have major sleep disturbances.

Adolescent↗

Sampling for airborne fluorouracil in a hospital drug preparation area.

Fluorouracil content was studied in air samples from a hospital pharmacy work area where a vertical laminar-airflow biological safety cabinet (BSC) vented into the work area was used for the preparation of antineoplastic drugs. The BSC was run 24 hours per day and used approximately 6 hours per day. During one 56-hour period and one 95-hour period, a portable pump delivering room air at 2 L/min was positioned 12 inches outside the BSC. Fluorouracil content in extracts from 0.5-micron Teflon filters housed in the pump was assayed by high-performance liquid chromatography. The assay's lower limit of fluorouracil detection was 0.2 ng/cu m air. In the 56-hour sampling period and the 96-hour sampling periods, 25.4 g and 25 g, respectively, of fluorouracil were prepared. No fluorouracil was detectable in the filter extracts. Use of an appropriate biological safety cabinet in conjunction with good aseptic technique and the recommended procedures for safe handling of antineoplastic drugs may reduce the potential for dispersal of drug into the pharmacy workroom environment.

Air Pollutants, Occupational↗

Combination therapy with diltiazem and propranolol: precipitation of congestive heart failure.

Although congestive heart failure has been reported with the combination of a beta blocker and either verapamil or nifedipine, it has not previously been reported for combination therapy that includes diltiazem. The following case documents the occurrence of clinical congestive failure in a patient with baseline left ventricular dysfunction and severe angina pectoris. Although the patients had tolerated propranolol therapy for years without difficulty, and high-dose diltiazem monotherapy with an excellent clinical response, the combination of diltiazem and propranolol resulted in the development of congestive heart failure. Thus, although generally well tolerated, given the suitable scenario of reduced left ventricular function, the combination of diltiazem and a beta blocker may adversely affect left ventricular performance.

Angina Pectoris↗

Methodological aspects of analysing human breast cancer cell lines by NMR spectroscopy.

In an attempt to identify the factors which might affect the measurement of water proton relaxation times in cultured cells, we have begun a long-term study of two human breast cancer cell lines, MDA-MB-231 and MDA-MB-435s. We tested growth rates and cell cycle distribution as intrinsic properties of the cells as well as methodological steps which might affect the measurement of T1 and T2. A detailed examination of the growth rates of the two cell lines, easily recognized as slow (231) and fast (435s) in culture, revealed that this attribute is difficult to correlate precisely with T1s or T2s. The reason is that the relaxation times are necessarily measured at one point in time while the growth rates are a summation of ongoing processes occurring over hours. Cell cycle distribution, on the other hand, can be measured simultaneously with the relaxation times by using cells quick-frozen from the same suspension. By this method, cell cycle distribution appears to be reflected through an effect on T1s. For example, cell pellets distributed 72:15:14 in G0G1:S:G2M has longer T1s (p less than 0.01) than those distributed 43:34:23 in G0G1:S:G2M. Regarding methodological factors, trypsin appeared to lower water content and T2s in the 231 cell line. Drift in the cell cycle distribution after sample preparation did not become significant until after 2 hours in the NMR tube. It was important to standardize the force and duration of centrifugation of the cell pellets to minimize the contribution of the suspending medium without affecting cell viability. We conclude that, given careful control of methodological factors, differences in T1 may reflect metabolic differences as demonstrated by T1 differences in cell pellets showing divergent cell cycle distribution.

Breast Neoplasms↗