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Biomedical subjects

R Keenan

Publications and source records attributed to R Keenan.

At least 37 records · Page 2Linked to original sources
PubMed1998

Future directions in esophageal cancer.

The incidence of esophageal cancer in the United States has been increasing in recent years. Since multimodality therapy for esophageal cancer has produced discouraging results, recent approaches have focused on molecular biological techniques, positron emission tomography, and minimally invasive surgery to improve pretreatment staging which will facilitate a more accurate assessment of new treatment. This article summarizes the results of studies investigating these approaches and outlines the strategy currently used at the University of Pittsburgh Medical Center.

DNA, Neoplasm↗
PubMed1997

Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine.

BACKGROUND: The purpose of this study was to correlate cytokine gene expression from bronchoalveolar lavage (BAL) cells and peripheral blood lymphocytes (PBL) with graft histology in recipients with persistent acute rejection treated with aerosolized cyclosporine (ACsA). METHODS: We measured mRNA for interleukin (IL) 6, interferon (IFN)-gamma, and IL-10 in recipients (1) without rejection (n=13), (2) with acute rejection that responded to pulsed methylprednisolone (n=7), and (3) with "refractory" acute rejection that failed to respond to conventional immunosuppression (n=17). In the latter group, ACsA was initiated. RESULTS: BAL cell IL-6 and IFN-gamma were highest in recipients with refractory rejection compared with recipients with steroid-responsive rejection and recipients with no rejection. Improvement in rejection histology occurred in 15 of 17 recipients who were treated with ACsA. IL-6 and IFN-gamma mRNA levels from BAL cells decreased during treatment with ACsA (median IL-6:actin ratio: before treatment, 0.40 vs. after treatment, 0.003, P=0.001; IFN-gamma:actin ratio: before treatment, 0.32 vs. after treatment, 0.04, P=0.001). PBL IL-6 and IFN-gamma mRNA expression also decreased during ACsA treatment after 180 days. Expression of IL-10 mRNA from BAL and PBL did not change during ACsA treatment (0.0 vs. 0.03 and 0.0 vs. 0.02, respectively). CONCLUSIONS: IL-6 and IFN-gamma mRNA expression from BAL cells was highest in those recipients with refractory histologic acute rejection. ACsA was associated with decreased IFN-gamma and IL-6 gene expression in BAL cells and PBL.

Acute Disease↗
PubMed1997

Minimally invasive surgical staging is superior to endoscopic ultrasound in detecting lymph node metastases in esophageal cancer.

OBJECTIVE: Endoscopic ultrasonography is frequently used to locally stage esophageal cancer, but few studies exist to validate its accuracy for lymph node metastases. Our objective was to compare endoscopic ultrasonography with video-assisted thoracoscopic and laparoscopic staging in evaluating lymph node metastases in esophageal cancer. METHODS: Twenty-six patients with potentially resectable esophageal cancer were identified by conventional imaging. Endoscopic ultrasonography was performed followed by laparoscopic and thoracoscopic staging, and locoregional staging was compared. RESULTS: In eight patients endoscopic ultrasonography indicated N0 disease, but laparoscopy and thoracoscopy documented N1 disease in six. In five of 26 (19%) obstruction prevented endoscopic ultrasonography; three had N1 by laparoscopy and thoracoscopy. Thirteen patients had N1 disease according to endoscopic ultrasonography, and 12 of 13 (92%) had N1 disease by laparoscopy and thoracoscopy. The sensitivity and specificity of endoscopic ultrasonography for nodal evaluation were 65% and 66%, respectively. Sensitivity decreased to 44% for lymph node metastases less than 1 cm. No instances of T4 disease were found by surgical staging when endoscopic ultrasonography indicated T3 disease. Endoscopic ultrasonography revealed no distant metastases in any patient, but in four of 26 (15%) laparoscopy identified liver metastases. CONCLUSIONS: The accuracy of endoscopic ultrasonography in the diagnosis of lymph node metastases in esophageal cancer was 65% and only 44% for lymph node metastases less than 1 cm diameter. Laparoscopy and thoracoscopy improved the accuracy of staging lymph node metastases in esophageal cancer and had the advantage of evaluating the thoracic and abdominal cavities for metastases.

Adenocarcinoma↗
PubMed1997

Determining if shared leadership is being practiced: evaluation methodology.

This article explores the use of a cognitive information-processing structure, mental models, to assess an organizational management change to shared leadership (SL). The purpose of this study was to describe the mental models of critical care nurses after the implementation of an SL management model. Scenarios based on daily clinical situations and measuring three SL concepts (empowerment, accountability, and partnership in decision making) were posed to critical care nurses in personal interviews. By using this evaluation methodology, nurse administrators can determine to what extent a new management change has been incorporated into daily nursing practice and in what areas to target further education and resources.

Critical Care↗
PubMed1996

Thoracoscopic laser bullectomy: a prospective study with three-month results.

One hundred forty-one patients were prospectively enrolled in a study of contact-tip laser bullectomy at four institutions. Ninety-one have had both preoperative and postoperative testing at 3 months. Nonsmoking patients with disabling dyspnea at less than 50 yards and with a forced expiratory volume in 1 second of 35% or less were enrolled. Testing included formal pulmonary function tests, arterial blood gasses, computed tomographic scans, ventilation/perfusion scans, echocardiograms, electrocardiograms, 6-minute walk testing, transdiaphragmatic pressures, and quality of life and dyspnea index questionnaires. A modest 16% improvement was noted in forced expiratory volume in 1 second (0.69 to 0.80 L), and there was a 29% improvement in 6-minute walk distances (655.2 to 846.3 feet). Oxygen use was completely discontinued in 16%. Risk factors for mortality included age, 6-minute walk distances, low diffusing capacity for carbon monoxide, high carbon dioxide tension, and high base excess. Minor improvement was judged from the dyspnea index and the Medical Outcome Study Short Form-36. Preoperative predictors of good outcome included heterogeneous disease, lack of carbon dioxide retention, and no emaciation (weight < 40 kg). Comparison of our results with those in the literature suggests that the improvement seen with the contact neodymium:yttrium-aluminum-garnet laser is not as good as that provided by the stapled techniques for volume reduction.

Acid-Base Imbalance↗
PubMed1994

Can immunohistological analysis of transbronchial biopsy specimens predict responder status in early acute rejection of lung allografts?

Acute cellular rejection (ACR) in the early posttransplant period is recognized as one predictor of the development of bronchiolitis obliterans in lung transplant recipients. Using an immunohistochemical panel of antibodies to CD3, L26, HLA-DR, collagenase IV, proliferating cell nuclear antigen (PCNA), KPI, and S100 antigens we analyzed cases of moderate ACR that did respond (n = 11) and that did not respond (n = 10) to bolus solumedrol therapy early in the postoperative period (< 100 days) to determine if we could identify predictors of histological response. Responders who had follow-up negative biopsies after therapy had biopsy specimens containing an average of 41.1% T cells (range, 15.1 to 69.8), 8.8% B cells (range, 0.6 to 20), 18.1% HLA-DR-positive cells (range, 3 to 29.6), 12.2% PCNA-positive cells (range, 2.7 to 22.6), 8.9% collagenase IV-positive cells (range, 0.7 to 20.9), and rare dendritic cells. Nonresponders who had follow-up biopsies that failed to show a significant change in rejection grade had biopsy specimens with the following average cell profiles: 35.8% T cells (range, 7 to 70.7), 21.6% B cells (range, 3.7 to 39.5), 14.2% HLA-DR-positive cells (range, 1.8 to 24.7), 11.4% PCNA-positive cells (range, 0.8 to 22), 12.6% collagenase IV-positive cells (range, 0.6 to 34.1), and occasional dendritic cells. Statistical analysis suggested that large numbers of B lymphocytes in early acute rejection predicts non-responsiveness to interventional immunosuppressive therapy and may indicate a significant role of humoral rejection in the behavior of early allograft rejection.

Antibodies, Monoclonal↗
PubMed1994

Mixed allogeneic chimerism in lung allograft recipients.

Microchimerism in lung allograft recipients was studied in the autopsies of nine female recipients of male lung grafts who had survived for more than 1 month after transplantation. Using a Y chromosome-specific probe tissues were studied for the presence of donor cells that had migrated beyond the graft itself. They were quantitated by cell counting to give absolute numbers of cells per organ volume. While donor cells were disseminated throughout the body, their numbers were small. These absolute numbers should be studied in a larger group of recipients to determine if they correlate with prognosis and the development of bronchiolitis obliterans.

Adult↗
PubMed1994

Amino acid losses in ileostomy fluid on a protein-free diet.

The contribution of losses via the gastrointestinal tract to maintenance amino acid requirements was assessed by collecting the ileostomy fluid of volunteers given a protein-free diet for 5 d. The subjects were eight adult men and women with terminal ileum ileostomies after ulcerative colitis. Four consecutive 24-h collections of both digesta and urine were made. On the last 2 d an antibiotic was given that suppressed microbial activity in the digesta and slightly reduced ileostomy outflow. Mean daily amino acid excretion in ileostomy fluid ranged from 32 mg/d for methionine to approximately 330 mg/d for aspartate and glutamate. These losses were compared with current international estimates of amino acid requirements. For most essential amino acids gastrointestinal losses accounted for 14-33% of daily maintenance requirements but for threonine the contribution was 61%.

Amino Acids↗
PubMed1994

Isolated glycerol kinase deficiency in a neonate.

Glycerol kinase deficiency occurs either as a relatively benign isolated enzyme deficiency, or as part of a syndrome resulting from a microdeletion in the p21 region of the X chromosome associated with congenital adrenal hypoplasia and/or Duchenne muscular dystrophy. Developmental delay is a consistent feature of the microdeletion syndrome but not of the isolated enzyme defect. We report a case of isolated glycerol kinase deficiency in a neonate presenting with hypotonia, apnea, mild developmental delay, and glyceroluria, without evidence of adrenal insufficiency or myopathy. A mild communicating hydrocephalus was noted on magnetic resonance imaging brain scan. It is important, therefore, to exclude glyceroluria in infants being investigated for apnea and hypotonia.

Apnea↗
PubMed1994

Efficacy of rapamycin, RS-61443 and cyclophosphamide in the prolongation of survival of discordant pig to rabbit cardiac xenografts.

OBJECTIVE: To evaluate the efficacy of two new immunosuppressive drugs, RS-61443 and rapamycin, alone and in combination with cyclophosphamide in the prolongation of heterotopic cardiac xenograft survival in a discordant neonatal pig to rabbit model. DESIGN: Animals were randomly assigned to receive rapamycin intravenously (1.0 mg/kg/day) or RS-61443 subcutaneously (160 mg/kg/day) commencing five days before surgery until rejection occurred. Cyclophosphamide, 20 mg/kg/day, was administered from one day prior to surgery. Combination of the above drugs (rapamycin 1.0 mg/kg/day and RS-61443 80 mg/kg/day) with and without treatment with cyclophosphamide was also evaluated. Trough blood concentrations of rapamycin and mycophenolic acid as well as rabbit antiporcine endothelial cell antibodies (immunoglobulin [Ig]M) were measured every second day from the commencement of drug therapy. RESULTS: The mean +/- SD survival time in control animals was 7.98 +/- 13.85 h (n = 11), with the majority of animals (n = 6) rejecting their grafts in less than 1 h. Rapamycin (11.5 +/- 9.5 h), RS-61443 (9.8 +/- 6.1 h), cyclophosphamide (17.9 +/- 16 h) alone, or the three drugs in combination (16.6 +/- 9.1 h) resulted in a trend to increase graft survival, which did not reach significance. In contrast, rapamycin and RS-61443 in combination (24.3 +/- 11.9 h) significantly (P < 0.05) prolonged graft survival. No significant (P > 0.05) decrease in rabbit antiporcine endothelial cell IgM concentrations was observed in all drug-treated groups; however, considerable variation was noted within each group. No relationship was found between trough concentrations of rapamycin and mycophenolic acid and xenograft survival or with a decrease in antibody concentrations. CONCLUSION: The data suggest that treatment modalities, in addition to the above drugs, is required for prolonged survival in cardiac xenografts in the discordant animal model used here.

Animals↗
PubMed1993

Single-dose pharmacokinetics of the new immunosuppressant RS-61443 in the rabbit.

The pharmacokinetics of mycophenolic acid (MPA) were investigated in six New Zealand white rabbits following (i.v.) and (s.c.) administration of RS-61443. Plasma concentrations of MPA were analyzed by high-performance liquid chromatography (HPLC). Model-dependent and -independent parameters were calculated. Mycophenolic acid is rapidly cleared with a terminal half-life of approximately 1.0 h. The volume of distribution subsequent to i.v. administration indicates minimal distribution into tissues. The mean residence time and volume of distribution were greater for the s.c. as compared to the i.v. route of administration. The insignificant difference in the area under the curve between the two dosage routes infers that the bioavailability of RS-61443-derived MPA by the former route of administration is comparable to the latter. Trough concentrations at the doses administered are below the detection limit of the HPLC procedure. The implications of these findings in relation to the therapeutic monitoring of the drug are discussed.

Animals↗
PubMed1993

Blood distribution of rapamycin.

Rapamycin (RAPA) is a potent new immunosuppressive drug. Although blood concentration monitoring of RAPA is being performed in preclinical and clinical trials, little is known regarding the blood distribution of the drug. Such information would have an impact on the medium used for analysis of the drug. The distribution of RAPA was investigated by spiking human whole blood having an initial temperature of either 4 degrees C or 22 degrees C with a constant amount of 3H-RAPA and increasing amounts of RAPA to a final concentration of 5-100 micrograms/L. The drug concentration spans the range seen when immunosuppressive doses of the drug are administered. This was followed by incubation of the blood at 37 degrees C for 0 to 60 min before separation of cells. The dpm in the resulting plasma and RBC fractions was determined by scintillation counting. The plasma to formed blood elements and plasma to whole blood ratios were 0.05 +/- 0.051 and 0.09 +/- 0.016, respectively (mean +/- SD, n = 50). The distribution did not exhibit any temperature or concentration dependence. The proportion of the drug among cellular components was as follows (mean % distribution +/- SD); RBC 94.5 +/- 4.9%; plasma 3.1 +/- 2.5%; lymphocytes 1.01 +/- 1.02%; and granulocytes 1.0 +/- 0.88%. The free or unbound fraction of RAPA over the plasma concentration range of 5-100 micrograms/L as determined by ultracentrifugation was 2.5 +/- 0.2%. The drug was found to be associated primarily with nonlipoprotein fractions in plasma. The results suggest from an analytical perspective that whole blood as compared with plasma would be the most suitable medium for analysis due to the higher concentrations found in the former.

Erythrocytes↗
PubMed1992

Smokeless tobacco abstinence effects and nicotine gum dose.

There were two experiments on abstinence from smokeless tobacco. The purpose of the first experiment was to determine abstinence effects from smokeless tobacco. The purpose of the second experiment was to examine the effects of different doses of nicotine gum on smokeless tobacco abstinence effects. The subjects were male Copenhagen smokeless tobacco users who underwent 3 days of baseline measurement while continuing to use smokeless tobacco ad libitum, and 5 days of the experimental condition. In the first experiment, the subjects were assigned randomly to one of two groups and compared: continuous smokeless tobacco users (n = 10), and deprivation plus no nicotine gum (n = 10). In the second experiment, subjects were assigned randomly and in a double-blind fashion to one of three groups and compared: (1) deprivation plus 0 mg nicotine gum (n = 20); (2) deprivation plus 2 mg nicotine gum (n = 20); and (3) deprivation plus 4 mg nicotine gum (n = 20). The first experiment showed significant increases upon abstinence for the following variables: (1) craving; (2) difficulty concentrating; (3) restlessness; (4) excessive hunger; (5) eating; (6) reaction time; (7) variability of reaction time and (8) total withdrawal scores for both the self-rated and the observer-rated forms. The second experiment showed that nicotine gum failed to significantly reduce smokeless tobacco abstinence effects, although those with high cotinine levels may receive some benefit from nicotine gum.

Adult↗
PubMed1991

Situational factors and patterns associated with smokeless tobacco use.

Situational factors and topographic features associated with smokeless tobacco use were examined. Male smokeless tobacco users (N = 30) were asked to record the time, activity, and internal states associated with each dip of tobacco use over the course of 10 days. Additionally, these subjects were asked to record the activity and internal state they were experiencing every hour for a 15-hr waking period to obtain baseline rates of these events. Serum and saliva samples were obtained to measure cotinine concentrations. The activities significantly associated with smokeless tobacco use included after a meal, while driving, and while watching television. The internal states associated with smokeless tobacco use were feeling relaxed and depressed. Factor analysis of the events showed factors which are different from those found among cigarette smokers. Examination of the topographic measures of smokeless tobacco use showed that the total dip duration per day was 283.5 min, with a range of 79.7-757.1 min. This measure, along with duration of dipping time (time from onset to offset of smokeless tobacco use during the day), may be the best predictors of nicotine exposure.

Adult↗