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Biomedical subjects

D Carney

Publications and source records attributed to D Carney.

At least 19 recordsLinked to original sources
PubMed2000

Mycosis fungoides bullosa simulating pyoderma gangrenosum.

A patient with mycosis fungoides (MF) bullosa had a rapidly growing, painful necrotic mass on the left ankle which extended by peripheral bulla formation, clinically resembling pyoderma gangrenosum. Histopathology confirmed MF bullosa with both intraepidermal and subepidermal bulla formation.

Antineoplastic Agents, Phytogenic↗
PubMed2000

[Effects of thrombin peptides on wound healing and proliferation and migration of normal human epidermal keratinocyte (NHEK)].

OBJECTIVE: To define the effects of thrombin peptides on wound healing and NHEK proliferation and migration. METHODS: A wound model was made with four 1.5 cm circular full thickness dermal excisions on the back of each Sprague-Dawley rat. 0.1 microgram (40 microliter) TP508 was applied to each circular excisional wound in 9 rats, the other 9 received saline only. Wound area was calculated with JAVA Jandel and IMAGE PRO software. NHEK945 proliferation was assessed by MTT assay and direct cell count with a Coulter Counter. Cell migration was determined by 48-well Boyden Chamber. Cells migrated onto the lower surface of the filter were assessed by a Chemi Imager 4000 Image Analyzer and expressed as spot density. RESULTS: Wound area in rats treated with TP508 was 73.7% and 45.4% of saline control on day 7 and 14, respectively. NHEK945 proliferation was accelerated after adding thrombin and TP508. The spot density of migrated cells was 76.7 plus minus 13.8 in medium alone. After adding 1 microgram/ml of thrombin and 10 microgram/ml of TP508, the spot density was 104.4 plus minus 12.2 and 109.4 plus minus 14.6, respectively. CONCLUSION: Results of this study suggest that both thrombin and TP508 have significant actions on wound healing and NHEK proliferation and migration, which is important in wound repair.

Animals↗
PubMed1999

Multiple sequential insults cause post-pump syndrome.

BACKGROUND: We hypothesize that post-pump syndrome (PPS) following cardiopulmonary bypass (CPB) can be caused by multiple minor insults and that the mechanism of PPS is a priming and subsequent activation of polymorphonuclear (PMN) leukocytes. In this study extensive pathophysiologic and morphometric assessment was undertaken in a porcine model of sequential insult PPS. METHODS: Pigs were anesthetized, placed on a ventilator, instrumented for measurements of hemodynamic function, and separated into five groups: (1) Control (n = 4)--surgery only, (2) CPB (n = 4)--placed on femoral-femoral hypothermic (28 degrees C) bypass for 1 h, (3) LPS (n = 6)--underwent sham CPB followed by infusion of low dose endotoxin [E. coli lipopolysaccharide (LPS-1 microg/kg)], (4) Heparin + protamine + LPS (HP + LPS, n = 4)--were heparinized without CPB for 1 h, following which protamine and LPS were infused and (5) CPB + LPS (n = 8)--subjected to both CPB and LPS. RESULTS: Only CPB + LPS resulted in acute respiratory distress typical of PPS as indicated by a significant decrease in PaO2 and increase in intrapulmonary shunt fraction (p<0.05). CPB + LPS significantly increased tissue density and the number of sequestered monocytes and PMNs (p<0.05) above all other groups. Alveolar macrophages (AM) increased equally in all groups receiving LPS. CONCLUSIONS: CPB primes the inflammatory system causing pulmonary PMN sequestration without lung injury. Exposure to an otherwise benign dose of endotoxin results in activation of the sequestered PMNs causing PPS. This study confirms that PPS can be caused by multiple minor insults.

Animals↗
PubMed1999

Quality-of-life measurement in advanced cancer: assessing the individual.

PURPOSE: Despite the increasing importance of assessing quality of life (QoL) in patients with advanced cancer, relatively little is known about individual patient's perceptions of the issues contributing to their QoL. The Schedule for the Evaluation of Individual Quality of Life (SEIQoL) and the shorter SEIQoL-Direct Weighting (SEIQoL-DW) assess individualized QoL using a semistructured interview technique. Here we report findings from the first administration of the SEIQoL and SEIQoL-DW to patients with advanced incurable cancer. PATIENTS AND METHODS: QoL was assessed on a single occasion using the SEIQoL and SEIQoL-DW in 80 patients with advanced incurable cancer. RESULTS: All patients were able to complete the SEIQoL-DW, and 78% completed the SEIQoL. Of a possible score of 100, the median QoL global score was as follows: SEIQoL, 61 (range, 24 to 94); SEIQoL-DW, 60.5 (range, 6 to 95). Psychometric data for SEIQoL indicated very high levels of internal consistency (median r =.90) and internal validity (median R(2) = 0.88). Patients' judgments of their QoL were unique to the individual. Family concerns were almost universally rated as more important than health, the difference being significant when measured using the SEIQoL-DW (P =.002). CONCLUSION: Patients with advanced incurable cancer were very good judges of their QoL, and many patients rated their QoL as good. Judgments were highly individual, with very high levels of consistency and validity. The primacy given to health in many QoL questionnaires may be questioned in this population. The implications of these findings are discussed with regard to clinical assessment and advance directives.

Adult↗
PubMed1999

Systemic inflammation induced by cardiopulmonary bypass: a review of pathogenesis and treatment.

The acute respiratory distress syndrome (ARDS) is a severe alteration in lung structure and function that develops secondary to a traumatic stimulus. When ARDS develops following cardiopulmonary bypass (CPB) it is know as postpump syndrome (PPS). ARDS can be caused by a single massive insult ("hit"); however, sequential minor insults ("hits") are more common clinically. The concept of multiple sequential insults causing ARDS has been termed the "two-hit" model of ARDS. The purpose of this article is to summarize our studies testing the hypothesis that PPS is caused by multiple sequential insults. To confirm our hypothesis, we developed a porcine model of "two-hit" PPS. Our model was composed of sequential benign insults, with CPB as the "first hit" and low dose of endotoxin as the "second-hit." It is our hypothesis that the mechanism of PPS is CPB-induced priming of polymorphonuclear leukocytes (PMNs) ("first-hit") with subsequent PMN activation by a second insult ("second-hit") such as endotoxin. Our model confirms this clinically relevant postulate, and we provide strategies to disrupt the inflammatory cascade leading to PPS.

Cardiopulmonary Bypass↗
PubMed1998

Expression of multidrug resistance-associated protein (MRP) in brain microvessel endothelial cells.

Multidrug resistance-associated protein (MRP) is a recently identified drug efflux transport system that actively transports organic acids and selected glucuronide or glutathione conjugates out of the cell. The current study presents, for the first time, both functional and biochemical data demonstrating the presence of MRP in the brain microvessel endothelial cells that form the blood-brain barrier (BBB). Using known MRP inhibitors, such as indomethacin and probenecid, fluorescein accumulation in primary cultured bovine brain microvessel endothelial cell (BBMEC) monolayers was significantly enhanced compared to control. The specificity of the MRP inhibitors on cellular fluorescein accumulation was confirmed using both MRP positive (Panc-1) and MRP negative (KBv) cell lines. Furthermore, western blot analysis using a specific antibody for MRP (MRPm6) and RT-PCR studies using a complementary sequence probe for human MRP demonstrate the expression of MRP in BBMEC. Previous studies have demonstrated the significance of the P-glycoprotein drug efflux transporter in the BBB. Given its function as a drug efflux transport system, it is anticipated that MRP in the BBB will also have an important role in limiting the exposure of the brain to many endogenous and exogenous compounds, including both toxic and therapeutic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Molecular biology of lung cancer.

Lung cancer is a major cause of mortality worldwide and the overall survival rate has not improved significantly in the past 20 years. Of the more than 150,000 new cases of lung cancer diagnosed in Europe every year, less than 10% of patients can be cured and enjoy long-term survival. The role of tobacco smoking as a cause of lung cancer has been conclusively established. Early diagnosis of lung cancer, based on conventional screening procedures using sputum cytology and chest radiography, has been so far unable to decrease lung cancer mortality. We discuss here the possibility that novel, more specific molecular markers, beside providing new understanding of the process of lung carcinogenesis, may also constitute new tools for early diagnosis allowing for screening of high-risk individuals, determination of prognosis, and identification of innovative treatments.

Chromosome Deletion↗
PubMed1998

Aerosolized surfactant improves pulmonary function in endotoxin-induced lung injury.

Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 microgram/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 +/- 19 mm Hg; LPS = 74 +/- 19 mm Hg, p < 0.05) while venous admixture (Q S/Q T) increased in these groups (LPS + PEEP = 43.3 +/- 3.9%; LPS = 47.7 +/- 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO2 (142 +/- 20 mm Hg) and rise in Q S/Q T (15.1 +/- 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 +/- 0.2 cells/6,400 micrometer2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 +/- 0.1 cells/6,400 micrometer2). LPS + PEEP + Sf (2.3 +/- 0.2 cells/6,400 micrometer2) significantly decreased while LPS + PEEP significantly increased (4.0 +/- 0.2 cells/6,400 micrometer2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.

Aerosols↗
PubMed1997

Primary hepatic lymphoma in a man with chronic hepatitis C.

We report the case of a middle-aged man who presented de novo with abdominal pain and hepatomegaly and was found to have positive serology for hepatitis C and subsequently a primary hepatic lymphoma. An increased incidence of primary hepatocellular cancer is well characterized in both cirrhotic and non-cirrhotic cases of chronic hepatitis C. The relationship between chronic hepatitis C and primary hepatic lymphoma remains obscure. It has been established that hepatitis C can sustain the clonal B-cell expansion that occurs in associated cryoglobulinaemia, and hepatitis C RNA has been detected within extrahepatic lymphoma tissue. Viral aetiologies for lymphoma are well characterized, such as Epstein-Barr virus (EBV) and human T-cell leukaemia virus (HTLV) I and II. Existing models of chronic infection causing lymphoma within the gastrointestinal tract include that of Helicobacter pylori and mucosa-associated lymphoid tumour of the stomach. Given the relatively low frequency of occurrence it may be prudent to perform a retrospective analysis on past cases of primary hepatic lymphoma in order to determine whether or not hepatitis C was present.

Antibodies, Neoplasm↗
PubMed1996

NCI-Navy Medical Oncology Branch cell line data base.

The cell line data base described in this paper includes both clinical information about the patients from whom the cell lines were derived and information about the in vitro analyses performed of the cell lines. The cell line data base has evolved as a part of a systematic effort by a research group at the NCI since 1976 to generate human cell lines as biological tools to study cancer and other diseases. The cell lines were generated from clinical specimens obtained as part of a series of Institutional Review Board-approved clinical protocols. The preponderance of the data is on lung cancer cell lines, though a broad range of other cancers are represented. A bank of over 300 human cell lines including cancer cell and in some instances autologous B-lymphoblastoid cells from the NCI-VA and NCI-Navy Medical Oncology Branch are reposited at the American Type Culture Collection. The cell lines are available for the research community. The entire data base is available on the American Type Culture Collection Web Site (WWW:http:@www.atcc.org/).

Biological Specimen Banks↗