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Biomedical subjects

P Davenport

Publications and source records attributed to P Davenport.

At least 19 recordsLinked to original sources

Cytokine removal during continuous renal replacement therapy: an ex vivo comparison of convection and diffusion.

BACKGROUND AND OBJECTIVES: It is unknown whether cytokine adsorption to the membrane during continuous renal replacement therapy is affected by the technique. Such knowledge might affect the choice of technique in vivo. Accordingly, we conducted an ex vivo study to test whether continuous veno-venous hemofiltration (CVVH) or continuous veno-venous hemodialysis (CVVHD) affect cytokine adsorption differently. SETTING: Laboratory attached to the Intensive Care Unit of a tertiary hospital. DESIGN: Six healthy human volunteers donated blood, which was incubated with endotoxin. Control blood was left at room temperature, and treatment blood was recirculated for eight hours through closed circuits using polyacrylonitrile membranes (AN69). The effect of CVVH and CVVHD on cytokine removal from the circuits was compared. MEASUREMENTS: The concentrations of interleukins (IL)-1beta, 6, 8, 10 and TNF were measured in the control samples, pre-and post-filter and in the effluent at baseline and hourly thereafter. The clearances by adsorption, and filtration were calculated. RESULTS: Control cytokine concentrations remained the same or increased slightly. Adsorption was the major mechanism of removal for all cytokines with the exception of IL-1beta, but the effect was short-lived. Peak adsorption generally occurred at baseline before the start of CVVH and CVVHD, with clearances ranging from 43.7 ml/min (for IL-8) to 7.6 ml/min (for IL-10). The time-weighted average total clearances during CVVH were 23.3, 4.3, 3.8, -2.0, and 15 ml/min for IL-8, IL-1beta, TNF, IL-6, and IL-10 respectively. The corresponding clearances during CVVHD were 19.0, 10.7, 2.7, 2.4, and 0.3 ml/min. IL-10 clearances were greater during CVVH than CVVHD (p=0.03). Non adsorptive CVVH clearance of IL-1beta was greater than CVVHD clearance, but this advantage was outweighed by an increased tendency of the membrane to release IL-1beta into the circuit during HF. CONCLUSIONS: The technique of solute removal had only a minor effect on the magnitude of cytokine adsorption, and neither technique had the advantage for all the measured cytokines.

Adsorption↗

Super high flux hemofiltration: a new technique for cytokine removal.

OBJECTIVE: To test whether hemofiltration using a hemofilter with large pores (super high flux hemofiltration) achieves effective cytokine removal. DESIGN: : Ex vivo study. SETTING: Laboratory of an intensive care unit in a tertiary hospital. PATIENTS AND PARTICIPANTS: Five healthy volunteers. INTERVENTIONS: Blood was spiked with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore polyamide super high flux hemofilter (nominal cut-off point: 100 kDa). Hemofiltration was conducted at 1 l/h or 6 l/h of ultrafiltrate flow. Samples were taken from the arterial, venous and ultrafiltration sampling ports. MEASUREMENTS AND RESULTS: Sieving coefficients (SC) above 0.6 were achieved for interleukin (IL)-1beta, IL-6 and IL-10 and SCs above 0.3 were achieved for IL-8 and TNF-alpha at 1 l/h. SCs of all cytokines (except IL-1) were reduced when the ultrafiltration rate was increased from 1 l/h to 6 l/h ( p<0.01), but cytokine clearances still increased ( p<0.01). The highest SC for albumin was 0.1 at 1 l/h and fell to 0.01 at 6 l/h. No adsorption of cytokines and albumin was observed. CONCLUSION: High volume ultrafiltration using a super high flux filter achieved cytokine clearances comparable to, or greater than, those currently achieved for urea during standard continuous renal replacement therapy.

Albumins↗

Necrotising fasciitis in an infant with congenital insensitivity to pain syndrome.

We present a rare case of necrotising fasciitis in an infant with congenital insensitivity to pain syndrome. The aetiology, diagnosis and management of necrotising fasciitis in children are compared with those in adults. In contrast to adults, children affected by necrotising fasciitis are usually previously healthy and have no predisposing factors. Early diagnosis, intravenous antibiotics and aggressive surgical debridement are mandatory for an optimal outcome.

Amputation, Surgical↗

Cytokine removal with a large pore cellulose triacetate filter: an ex vivo study.

OBJECTIVE: To test the hypothesis that hemofiltration using a new large pore cellulose triacetate hemofilter can achieve effective ultrafiltration of cytokines. DESIGN: Ex-vivo study. SETTING: Laboratory of Intensive Care Unit in tertiary hospital. SUBJECTS: Six healthy volunteers. INTERVENTIONS: Blood from 6 volunteers was incubated for 4 hours with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore cellulose triacetate hemofilter (nominal cut-off point: 60 kilodaltons). Hemofiltration was conducted at 1 L/h or 6 L/h of ultrafiltrate (UF) flow at the start of extra-corporeal circulation, and after 2 and 4 hours. Samples were taken from the arterial, venous and UF sampling ports. MEASUREMENTS AND MAIN RESULTS: IL-Ibeta, IL-6, IL-8, IL-10, TNFalpha, and albumin were measured. Sieving coefficients (SC) above 0.6 were achieved for IL-Ibeta and IL-6 and SCs above 0.3 were achieved for IL-8 and TNF-alpha at 1 L/h. Sieving coefficients of all cytokines (except IL-10, p=0.22) were reduced when the ultrafiltration rate was increased from IL/h to 6 L/h (p<0.01), but the increase in ultrafiltration rate resulted in an overall increase in the clearance of all cytokines (p<0.001). The highest SC for albumin was 0.07 at 4 hours at 1 L/h, and fell to 0.01 at 6 L/h. The SCs for IL-8 fell at 4 hours (p<0.01), but the SCs for other cytokines did not change. No adsorption of cytokines and albumin was observed. CONCLUSION: High volume hemofiltration (HVHF) using a new large pore cellulose triacetate filter achieved cytokine clearances greater than those reported with currently available hemo filters.

Albumins↗

High-volume haemofiltration in human septic shock.

OBJECTIVE: To evaluate whether high volume haemofiltration improves haemodynamics and affects serum cytokine and complement concentrations in human septic shock. DESIGN AND SETTING: Randomized cross-over clinical trial in a tertiary intensive care unit. PATIENTS: Eleven patients with septic shock and multi-organ failure. INTERVENTIONS: Patients were assigned to either 8 h of high-volume haemofiltration (HVHF; 6 l/h) or 8 h of standard continuous veno-venous haemofiltration (CVVH; 1 l/h) in random order. MEASUREMENTS AND MAIN RESULTS: We measured changes in haemodynamic variables, dose of norepinephrine required to maintain a mean arterial pressure greater than 70 mmHg and plasma concentrations of complement anaphylatoxins and several cytokines. An 8-h period of HVHF was associated with a greater reduction in norepinephrine requirements than a similar period of CVVH (median reduction: 10.5 vs. 1.0 microg/min; p = 0.01; median percentage reduction: 68 vs. 7%; p = 0.02). Both therapies were associated with a temporary reduction (p < 0.01) in the plasma concentration of C3a, C5a, and interleukin 10 within 2 h of initiation. HVHF was associated with a greater reduction in the area under the curve for C3a and C5a (p < 0.01). The concentration of the measured soluble mediators in the ultrafiltrate was negligible. CONCLUSIONS: HVHF decreases vasopressor requirements in human septic shock and affects anaphylatoxin levels differently than standard CVVH.

APACHE↗

Inspiratory pressure threshold training for glottal airway limitation in laryngeal papilloma.

A single-subject design was used to determine if inspiratory pressure threshold training increases inspiratory muscle strength and reduces the sensation of dyspnea during exercise and speech. The subject was a 23-year-old female with congenital juvenile papilloma which has been in remission for 10 years. A 4-week inspiratory muscle training program was implemented using an inspiratory pressure threshold trainer. The pressure threshold of the trainer was set by the experimenter. The pressure threshold setting of the trainer was based on a percentage of the subject's maximum inspiratory pressure measured prior to training. The average range of the pressure threshold was 40 to 70 cmH2O. In order for inspiratory air to flow, the subject generated inspiratory pressure, independent of airflow rate. Maximum inspiratory pressure (MIP) was the dependent variable used as the index of inspiratory muscle strength. Exercise dyspnea was a dependent variable rated by the subject during a progressive treadmill test. Dyspnea associated with speech was rated following production of a comfortable and loud speech task. MIP increased by 57% following the training program with a 2-scale point reduction in the perception of dyspnea during exercise. Dyspnea during loud speech decreased from moderate to mild. The changes in dyspnea, both during exercise and speech, are directly related to inspiratory muscle strengthening. The results suggest that inspiratory muscle training may improve respiratory related function in patients with restrictive upper airway disorders.

Adult↗

Monitoring brain PO2, PCO2, and pH during graded levels of hypoxemia in rabbits.

Brain ischemia and hypoxia are of concern when they occur following traumatic brain injury because they frequently result in potentially preventable secondary brain damage. In this study, we examined the ability of an implantable catheter (Paratrend 7; Diametrics Medical, St. Paul, MN) to continuously measure brain tissue pH, PCO2, and PO2 during graded levels of hypoxia. Values obtained from this catheter were compared with simultaneous measurements of arterial and sagittal sinus blood. As expected, there was a good correlation between the changes in pH, PCO2, and PO2 in brain tissue and sagittal sinus blood. Brain tissue PO2 was numerically lower than sagittal sinus blood at all inspired levels of oxygen. These data suggest that the Paratrend 7 may be useful in monitoring brain tissue oxygen tension in patients at risk for regional cerebral ischemia and hypoxia.

Animals↗

Psychosocial status of women requesting breast reduction surgery as compared with a control group of large-breasted women.

The breast has special significance for women but unlike women seeking breast augmentation little research has been carried out on those seeking breast reduction. The few studies to date have not used well-recognized instruments nor appropriate controls. The present study compared 33 patients on a waiting list with 22 large-breasted controls using a semistructured questionnaire and well-validated instruments. Patients experienced greater physical and psychological difficulties but similar social difficulties as compared with the control group. Patients were also more anxious and depressed and had poorer self-esteem, body image, interpersonal functioning, and health status. This study confirms the high psychological morbidity of patients seeking breast reduction.

Adult↗

The evaluation of velopharyngeal function using flexible nasendoscopy.

Nasendoscopy is an essential tool in assessing the dynamic function and structure of the velopharyngeal sphincter during speech and swallowing. Flexible fibre-optic nasendoscopy has been used by the cleft palate team at Withington Hospital, Manchester since 1989. Seventy-six patients were referred between 1989 and 1994 for evaluation of velopharyngeal function during speech. Flexible nasendoscopic evaluation was attempted in 50 patients, and successfully carried out in 43 patients. The age range was four years to 77 years (mean 21 years). The patients were divided into two groups: Group 1 consisting of patients with cleft palate and Group 2 comprised of patients with non-overt cleft palate-related velopharyngeal dysfunction of various aetiologies; such as, submucous cleft, post-tonsillectomy, post-adenoidectomy, neurological and post-traumatic. Based on the findings on nasendoscopy, videofluoroscopy and clinical speech/voice analysis the following treatment options were recommended: 17 (40 per cent) for pharyngoplasty, five (11 per cent) for revision pharyngoplasty, 15 (35 per cent) for speech therapy, four for an obturator and one for tonsillectomy. Two previously undetected submucous clefts were diagnosed.

Adolescent↗

Tissue factor pathway inhibitor expression in atherosclerosis.

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF) -initiated coagulation and may play a role in regulating coagulation in atherosclerotic plaques. The expression of TFPI protein and mRNA was examined by immunohistology and in situ hybridization in normal human and rabbit arteries, in human carotid arteries with advanced atherosclerosis, and in atherosclerotic aortas from cholesterol-fed rabbits. In normal human and rabbit arteries, TFPI protein and mRNA were detected in the adventitial layer but were undetectable in the luminal endothelium. In the medial smooth muscle layer of rabbits, weak expression of TFPI mRNA, but not protein, was detected; in that of humans, neither TFPI mRNA nor protein was detectable. In atherosclerotic arteries, TFPI protein and mRNA were detected in three of six internal carotid plaques from patients undergoing endarterectomy, and mRNA alone was detected in one further specimen. TFPI protein was found in areas of the plaque where TF was abundant and colocalized with macrophages, suggesting that these cells are responsible for TFPI synthesis. TFPI protein and mRNA were also detected in fatty-streak lesions in 18 of 19 rabbits fed a high-cholesterol diet for periods between 4 and 16 weeks. In these macrophage-rich lesions, expression of TFPI protein and mRNA was most intense at the base of the plaques. These studies suggest that TFPI is expressed in the adventitial layer of large arteries and that in atherosclerotic vessels, TFPI is expressed by macrophages in focal areas throughout the plaque. Local production of TFPI may regulate procoagulant activity and thrombotic events within atherosclerotic plaques.

Aged↗

Interleukin-1 receptor antagonist: characterisation of its gene expression in rabbit tissues and large-scale expression in eucaryotic cells using a baculovirus expression system.

The gene expression of rabbit interleukin-1 receptor antagonist (RbIL-lra) was examined in rabbit tissues. RNA was isolated from heart, lung, kidney, muscle, liver, spleen, brain, and peripheral blood monocytes (PBMs), and RbIL-lra mRNA was identified as a single species by Northern analysis using a RbIL-lra probe. RbIL-lra was abundantly expressed in lung, brain, heart, and liver, expressed at low levels in spleen, and undetectable in kidney and unstimulated PBMs. Expression of large scale recombinant production of RbIL-lra was achieved by subcloning the cDNA into a baculovirus expression vector. Recombination of this vector was completed with the BacPAK6 baculovirus genome. The recombinant virus, containing the RbIL-lra cDNA, was used to infect Spodoptera frugiperda (Sf21) insect cells in a spinner flask system and in monolayers in cell culture flasks. Recombinant rabbit IL-lra (rRbIL-lra) was secreted into the culture medium in this system at very high levels (35 mg/l). The protein was identified by reducing SDS-PAGE electrophoresis, was variably glycosylated and had a molecular weight between 19-25 kDa. It was then purified by size exclusion HPLC on a Du Pont Gf-250 column. The rRbIL-lra was demonstrated to be functionally active by inhibiting recombinant human IL-1 alpha in a mouse thymocyte proliferation assay. 20 ng/ml (6.7 U/ml) of rRbIL-lra inhibited 95% of the activity of 2 ng/ml IL-1 alpha.

Animals↗

Interleukin-8 production by macrophages from atheromatous plaques.

Interleukin-8 (IL-8) is a chemotactic peptide produced by macrophages that may be involved in the recruitment of inflammatory cells into atherosclerotic plaques. In vitro, IL-8 production by macrophages isolated from carotid plaques (1240 +/- 510 pg.10(5) cells-1.24h-1, mean +/- SEM, n = 6) and noncarotid plaques (4312 +/- 1588 pg.10(5) cells-1.24 h-1, n = 9) was significantly greater than IL-8 production by blood monocytes isolated from the same patients (526 +/- 278 pg.10(5) cells-1.24 h-1, n = 6, P < .05 and 726 +/- 384 pg.10(5) cells-1.24 h-1, n = 9, P < .01, respectively). IL-8 produced by atherosclerotic macrophages was demonstrated to be biologically active in a neutrophil chemotaxis assay. IL-8 mRNA was detectable in plaque macrophages and blood monocytes from these patients, but blood monocytes from normal donors did not exhibit detectable IL-8 mRNA. IL-8 mRNA was localized in macrophage-rich areas of atherosclerotic plaques by in situ hybridization. These studies demonstrate that macrophages from atherosclerotic plaques show an enhanced capacity to produce IL-8 compared with normal and patient blood monocytes and that macrophages are a major site of IL-8 mRNA production in atherosclerotic plaques. These results provide further evidence for a proinflammatory role for macrophages in atherosclerosis.

Aged↗

Three-dimensional magnetic resonance imaging evaluation of pediatric tracheobronchial tree.

Magnetic resonance imaging (MRI) of the airway has recently emerged as a diagnostic tool for evaluating tracheobronchial obstruction in pediatric patients. Computer-assisted reconstructions of transaxial images have enabled three-dimensional reconstructions of the airway to be manipulated in any plane and visualized in relation to adjacent anatomical structures. Eight patients in whom magnetic resonance imaging was used to diagnose a variety of airway obstructive lesions are presented. A protocol for the evaluation of pediatric tracheobronchial obstruction is presented, with the role of three dimensionally reconstructed MR imaging emphasized.

Airway Obstruction↗

Atheromatous plaque macrophages produce plasminogen activator inhibitor type-1 and stimulate its production by endothelial cells and vascular smooth muscle cells.

The capacity of macrophages to influence directly and indirectly fibrinolytic processes in atherosclerosis was studied using macrophages isolated from atherosclerotic plaques of patients undergoing surgical repair of distal aortic and femoral arteries. These cells were characterized by their morphology, adherence, esterase positivity, and expression of CD14 antigen. Production of plasminogen activator inhibitor type-1 (PAI-1) by plaque macrophages (6.7 +/- 2.7 ng/10(5) cells/24 hours [mean +/- SEM]) was significantly greater than PAI-1 production by blood monocytes isolated simultaneously from the same patients (1.8 +/- 1.5 ng/10(5) cells/24 hours). Production of tissue type plasminogen activator and urokinase type was not augmented compared to blood monocytes. Conditioned medium from cultured plaque macrophages significantly increased production of PAI-1 by endothelial cells (85 +/- 11% above basal) and vascular smooth muscle cells (25 +/- 10%) in vitro. This response was significantly greater than the response to monocyte-conditioned medium (endothelial cells 38 +/- 11%, vascular smooth muscle cells 2.5 +/- 2.0%). Stimulation of endothelial cell PAI-1 production by macrophage-conditioned medium was partially inhibitable by a monoclonal antibody to transforming growth factor-beta. Tissue type plasminogen activator production by endothelial cells and vascular smooth muscle cells was not affected by plaque macrophage- or monocyte-conditioned medium. Urokinase type plasminogen activator production by endothelial cells and vascular smooth muscle cells was undetectable in control medium and was augmented to similar levels in response to plaque macrophage- and monocyte-conditioned media. These results demonstrate upregulation of PAI-1 production by macrophages in atheromatous plaques and the capacity of soluble products from plaque macrophages to upregulate PAI-1 production by endothelial cells and vascular smooth muscle cells in vitro. These data suggest that macrophages in atherosclerotic plaques may inhibit thrombolysis both directly and indirectly by effects of their soluble products on endothelial cells and vascular smooth muscle cells.

Aged↗

The Victorian population projection framework.

"The Victorian Department of the Treasury has responsibility for preparation of demographic forecasts for use by state government departments and agencies. This paper provides a detailed description of the projection system and models developed by Treasury to produce population and household forecasts for the state, statistical divisions and Statistical Local Areas of Victoria [Australia]. Particular emphasis is given to use of a 'tops down' approach to integrate projections at different geographic levels, methods of reconciling forecasts of household growth with land supply and techniques used to project the inter-SLA migration flows in a multi-regional cohort-component framework."

Agriculture↗

Leucocyte numbers and quality: their effect on viscosity.

Leucocyte suspension viscosity was measured using cells from a number of leukaemias. Samples from individuals with acute myelomonocytic and myeloid leukaemias, and chronic myelogenous and chronic lymphatic leukaemias were examined for their viscosity and flow properties. Leucocytes were suspended in native plasma and the effect of variable leucocyte numbers in the ranges seen in some leukaemias (100-600 x 10(9)/l) examined at different shear stresses. The effect of MCV was also determined in relation to viscosity. The results showed an increasing order of viscosity from the leucocytes of chronic lymphatic leukaemia through chronic myelogenous and acute myeloid leukaemia to the acute myelomonocytic variety. This bears some relation to the mean corpuscular volume, but confirms the fact that at high numbers of cells, patients with acute myelomonocytic, and to a lesser extent the myeloid leukaemias, are at considerable risk of blood hyperviscosity.

Blood Viscosity↗

Twelve years' experience of computer-aided diagnosis in a district general hospital.

This paper describes experience in a modern district general hospital with a small desktop system for computer-aided diagnosis of acute abdominal pain, over a 12-year period involving 5512 cases. When compared with a baseline year (1973) in which unaided performance was monitored, during an initial study period (1974-76) the diagnostic accuracy of junior staff rose by between 10 and 15%. This higher performance level was then maintained for a decade (1976-86) despite changes in staff. The perforation rate among appendicitis cases fell from 27% to 12.5%, accompanied by a smaller fall in negative laparotomy rates. The saving in surgical bednights devoted to acute abdominal pain was approximately 15%, and the notional cost of resources saved during the first 6 years of operation was 120,000 pounds. Other hospitals have shown--in the short term--benefits similar to those obtained at Airedale District General Hospital. The long-term benefits of the system at Airedale reinforce the conclusions of the earlier short-term trials that a comparable system should probably be offered to all DGHs in the UK, not as an exercise in 'artificial intelligence' but as an effective continuing stimulus to good clinical practice.

Abdominal Pain↗

Treatment of metastatic melanoma by 24-hour DTIC infusions and hemibody irradiation.

Forty-three patients with widely metastatic melanoma were studied. Visceral metastases were present in 79% of the patient group, including five patients with brain metastases. No patients were excluded because of "early death," etc., from analysis. All 43 patients received 24-hour DTIC infusions. Dosages for individual patients ranged from 350 mg/M2 to 2.5 g/M2, a maximum of 6 courses being given. A total of 155 courses was administered. Hemibody irradiation (HBI) was delivered after 1 or 3 courses of DTIC to the area of maximum disease in 23 patients. Fourteen of the 43 patients responded to DTIC chemotherapy (with one complete response), a response rate of 33%. Seven of the chemotherapy responders also responded in other sites to subsequent HBI, a response rate of 30% (7/23). No patient responded to HBI and not to DTIC. Median survival was 4 months (range, 1-15), and nine patients are still alive at 3 to 15 months. Toxicity was generally mild, although there was one possible treatment-related death. Further exploration of DTIC infusion chemotherapy and HBI would be of interest.

Adult↗