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Biomedical subjects

P Hillyer

Publications and source records attributed to P Hillyer.

8 recordsLinked to original sources
PubMed2003

Chemokines, chemokine receptors and adhesion molecules on different human endothelia: discriminating the tissue-specific functions that affect leucocyte migration.

The selective accumulation of different leucocyte populations during inflammation is regulated by adhesion molecules and chemokines expressed by vascular endothelium. This study examined how chemokine production and the expression of adhesion molecules and chemokine receptors vary between endothelia from different vascular beds. Human saphenous vein endothelium was compared with lung and dermal microvascular endothelia and with umbilical vein endothelium and a bone-marrow endothelial cell line. All endothelia produced CCL2 and CXCL8 constitutively, whereas CXCL10 and CCL5 were only secreted after tumour necrosis factor (TNF)-alpha or interferon (IFN)-gamma stimulation. In combination with TNF-alpha, IFN-gamma suppressed CXCL8 but enhanced CCL5 and CXCL10, whereas transforming growth factor (TGF)-beta reduced secretion of all chemokines. Basal chemokine secretion was higher from umbilical vein than other endothelial cells. Chemokine receptors, CXCR1, CXCR3 and CCR3, were present on all endothelia but highest on saphenous vein. CCR4, CCR5, CCR6, CXCR2, CXCR4 and CXCR5 were also detected at variable levels on different endothelia. The variation between endothelia in chemokine secretion was much greater than the variations in adhesion molecules, both on resting cells and following cytokine stimulation. These results indicate that it is the tissue-specific variations in endothelial chemokine secretion rather than variations in adhesion molecules that can explain the different patterns of inflammation and leucocyte traffic seen in non-lymphoid tissues.

Bone Marrow↗
PubMed2000

Noninflammatory phagocytosis of monosodium urate monohydrate crystals by mouse macrophages. Implications for the control of joint inflammation in gout.

OBJECTIVE: We have hypothesized that the process of monocyte to macrophage differentiation may alter the inflammatory response of mononuclear phagocytes to the uptake of monosodium urate monohydrate (MSU) crystals. METHODS: Eight mouse monocyte/macrophage cell lines were arranged in increasing order of differentiation, as judged by expression of the macrophage markers F4/80 and BM 8 and by phagocytic capacity. Secretion of tumor necrosis factor alpha (TNFalpha) in response to MSU was measured by enzyme-linked immunosorbent assay. RESULTS: The panel of monocyte/macrophage cell lines revealed a close linkage between the state of differentiation and the capacity of the cells to ingest MSU crystals. TNFalpha production, however, was not linked to phagocytic ability. Peak TNFalpha levels were synthesized by cells at an intermediate state of differentiation (3.2-14.1 ng/ml), whereas mature macrophages, which efficiently phagocytosed crystals, did not secrete TNFalpha. Mature cell lines produced TNFalpha when stimulated with zymosan (5.9-6.2 ng/ml), but this was abolished by coincubation with MSU crystals. Suppression of the zymosan response was not due to apoptosis or steric hindrance by MSU crystals. Culture supernatants from mature macrophages did not stimulate endothelial cell activation, in contrast to MSU-treated cells at an earlier stage of differentiation, which stimulated intercellular adhesion molecule 1 expression on sEND endothelioma cells through the release of TNFalpha (inhibited 80.6% by anti-TNFa). CONCLUSION: We demonstrated that phagocytosis and TNFalpha production are distinct events in the response of mononuclear phagocytes to urate crystals, and these events can be distinguished at the level of macrophage differentiation. The noninflammatory removal of urate crystals by mature macrophages defines a new pathway that may be important in controlling the development of acute gout in patients with hyperuricemia.

Animals↗
PubMed1998

Integrilin prevents prolonged bleeding times after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass reduces platelet number and function, increases postoperative bleeding time, and is the major, unsolved cause of nonsurgical bleeding after open heart operations. Temporary inhibition of platelet function during cardiopulmonary bypass (platelet anesthesia) protects platelets and reduces postoperative bleeding time and bleeding. METHODS: Integrilin, a short-acting, reversible platelet glycoprotein IIb/IIIa inhibitor was studied in 28 baboons that had 60 minutes of normothermic cardiopulmonary bypass using peripheral cannulas. A control group, two groups that received different doses of Integrilin, and a group that received a combination of Integrilin and low-dose Iloprost were studied. Blood samples for platelet count, aggregation to adenosine diphosphate, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, and fibrinopeptide A were obtained at seven time points. Template bleeding times were measured before and at five intervals after cardiopulmonary bypass. RESULTS: Both doses of Integrilin and the combination of Integrilin and Iloprost significantly protected platelet number, inhibited the response to adenosine diphosphate, and reduced postoperative bleeding times, but they did not reduce beta-thromboglobulin release except in the high-dose Integrilin group. Thrombin formation and activity were qualitatively, but not significantly, reduced in all treatment groups. Bleeding times were not significantly different from baseline at the time protamine was given in the combination group and 60 minutes after protamine administration in all treatment groups. CONCLUSIONS: Integrilin alone or in combination with Iloprost significantly reduces platelet activation during cardiopulmonary bypass and produces normal or near-normal bleeding times at the time protamine is given.

Animals↗
PubMed1989

Evaluation of a user-operated patient-side blood gas and chemistry monitor in children undergoing cardiac surgery.

A study was performed to evaluate a user-operated patient-side blood gas and chemistry monitor (GEM-STAT, Mallinckrodt Sensor Systems, Ann Arbor, MI) for the first time in a group of infants and children with congenital heart disease undergoing cardiac surgery. Paired blood samples from 18 patients were analyzed by the test instrument and by standard clinical laboratory instruments. One failure of the test instrument, malfunction of a cartridge, occurred during the evaluation. The integrated and external quality control functions gave readings within the manufacturer's tolerance. The differences between the measurements obtained using the GEM-STAT and the standard laboratory instruments for five of the six variables are summarized as follows (mean +/- SD, units of measure, number of samples): pH (-0.017 +/- 0.02, 132), PaCO2 (-1.90 +/- 3.3 mm Hg, 130), hematocrit (-1.3 +/- 2.3%, 129), potassium (-0.17 +/- 0.20 mmol, 112) and sodium (-2.0 +/- 3.3 mmol, 112). The mean difference in the measurements of PaO2 in the clinically important range defined by the upper quality control limit for oxygen tension of 172 mm Hg for the GEM-STAT is: (-0.20 +/- 7.26 mm Hg, 51). The mean difference between the measurements for PaO2s below the lowest quality control point (60 mm Hg) was (-2.3 +/- 5.5 mm Hg, 30). The values for all variables obtained from the GEM-STAT during the trial period, with the exception of the PaO2 less than 60 mm Hg, showed good correlation with the laboratory over the clinically useful range.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Chemical Analysis↗
PubMed1980

External stent for repair of secondary tracheomalacia.

Tracheomalacia was created in anesthetized piglets by submucosal resection of 3 to 5 tracheal cartilages. Measurements of airway pressure and flow showed that expiratory airway resistance is maximal at low lung volumes and is significantly increased by creation of the malacic segment. Cervical flexion increases expiratory airway resistance, whereas hyperextension of the neck reduces resistance toward normal. External stenting of the malacic segment reduces expiratory airway resistance, and the combination of external stenting and hyperextension restores airway resistance to normal except at low lung volume. Two patients with secondary tracheomalacia required tracheostomy and could not be decannulated after the indication for the tracheostomy was corrected. Both were successfully decannulated after external stenting of the malacic segment with rib grafts. Postoperative measurements of expiratory pulmonary resistance show a marked decrease from preoperative measurements. External stenting of symptomatic tracheomalacia reduces expiratory airway resistance by supporting and stretching the malacic segment and is preferable to prolonged internal stenting or tracheal resection.

Airway Resistance↗
PubMed1978

Relationship between platelet count and cardiotomy suction return.

A simple, inexpensive, accurate method of measuring the amount of blood returned by the cardiotomy suction system was devised and calibrated. Preoperative and postoperative platelet counts were obtained in 76 patients with congenital heart disease in whom the amount of cardiotomy suction return was measured. The mean percentage of total perfusate returned by the cardiotomy suction system was 8.9%. Both postoperative platelet count and the percentage change between preoperative and postoperative platelet counts correlated with the amount of blood returned by the cardiotomy suction system, time on bypass, and the percentage of total perfusate aspirated by the system.

Adolescent↗
PubMedDate not supplied

Use of the spiral coil membrane oxygenator during open heart surgery in infants and children.

The spiral coil membrane oxygenator was used without an arterial line filter during short term total cardiopulmonary bypass in 50 infants and children. The compact oxygenator proved to be efficient and reliable, was easy to operate in a simple perfusion circuit, has a high flow rate to priming volume ratio and eliminated gaseous emboli. During perfusion, platelet counts and fibrinogen concentrations descreased 51 and 31% respectively. Coagulation studies in eight infants less than 15 kilograms perfused with the membrane oxygenator system did not differ from those in 7 infants perfused by a bubble oxygenator system.

Adolescent↗