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Biomedical subjects

P Gosling

Publications and source records attributed to P Gosling.

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

The cellular, immune, and metabolic response to trauma.

The major challenge in treatment of the multiple trauma victim has shifted from early and effective resuscitation to treatment of the host response to injury. Patients surviving for the first 24 h after major injury as a result of effective resuscitation remain at risk of progressive organ failure and death from what appears to be an uncontrolled inflammatory process. A septic cause is frequently not identifiable, yet the response is as if the patient were infected. While organ-supportive measures such as mechanical ventilation, extracorporeal membrane oxygenation, renal replacement therapies, and total parenteral nutrition help to maintain tissue substrate delivery and metabolite removal, these therapies eventually fail if the microvaculature ceases to function. As the soluble and cell-mediated pathways of the inflammatory response are now being unraveled, possible interventions designed to attenuate selected elements of the inflammatory pathways are being developed. These measures include antioxidants, enzyme inhibitors, pharmacological agents, antibodies both to soluble mediators and cell surface receptor antagonists. Most of these interventions are at the experimental stage and so far have only met with limited clinical success. A major problem with attenuation of the inflammatory response is the overlap of inflammatory pathways, such that modulation of one or two is unlikely to be of benefit in a patient with major injuries. In addition, the speed of these responses, once initiated, requires that therapies have to be administered very soon after injury to be effective. However, the tremendous increase in knowledge of the inflammatory response, and the increasing sophistication of laboratory science that can provide both assessment of mediators of inflammation and the patients' response to the inflammatory process allows early identification of patients at risk of post-trauma organ failure. Armed with this knowledge, treatment can be tailored to each patients' individual response to injury, and when definitive antiinflammatory regimes are available, patients who can benefit from this treatment can be identified rapidly.

Animals↗
PubMed1997

Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response?

OBJECTIVES: To identify a stable biochemical marker of disease severity in patients with intermittent claudication and to use these findings to assess the effect of therapeutic exercise training. DESIGN: Case-control study: prospective randomised-controlled trial of exercise training. MATERIALS AND METHODS: Plasma fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR) were measured in 67 claudicants and 15 controls. Twenty-two patients were randomised to supervised exercise training and 17 randomised to observation. Subjects were reviewed at 3, 6 and 12 months. RESULTS: The median (interquartile range) baseline fibrinogen was 3.7 g/l (3.3-4.25) in claudicants and 3.5 g/l (2.9-3.95) in controls (p = 0.045); CRP was 4.7 mg/l (2.2-9.0) and 2.1 mg/l (1.0-2.8), respectively (p < 0.0001); SAA was 72 mg/l (35-132) and 30 mg/l (20-89) (p = 0.0009). Claudicants showed an increased urinary ACR following treadmill exercise (Wilcoxon, p < 0.0001) with no change in controls. Exercise training reduced SAA at 6 months, CRP at 3 months and progressively attenuated the post-exercise increase in ACR. No similar changes were found in controls. CONCLUSIONS: Repetitive low-grade inflammatory events in claudicants lead to elevation of serum acute-phase proteins. Exercise training is associated with symptomatic improvement and reduction inflammatory markers. The concern that exercise has adverse systemic effects therefore seems to be unjustified.

Aged↗
PubMed1997

Prediction of posttraumatic adult respiratory distress syndrome by albumin excretion rate eight hours after admission.

BACKGROUND: Adult respiratory distress syndrome (ARDS) in trauma victims carries a mortality on the order of 50%. An early feature is an increased capillary permeability causing an extravasation of plasma proteins and water, leading to interstitial edema. In the kidney, the increase in microvascular permeability is manifested as increased albumin excretion detectable by sensitive immunoassay. METHODS: Forty seven trauma victims were studied for 5 days; 32 of them had Injury Severity Scores > 18. A diagnosis of ARDS was made on the recommendations of the American-European Consensus Conference on ARDS (1994). Eight patients developed ARDS, five developed pulmonary dysfunction, and the remainder showed no significant pulmonary abnormality. RESULTS: Using the near patient urine albumin immunoassay, albumin excretion rate (AER) was measured after admission. For patients with Injury Severity Score > 18, the median (95% confidence interval) AER 8 hours after admission was 63 (range, 40-99) microg per minute for those without impaired lung function and 339 (range, 162-454) microg per minute for those in the combined ARDS and pulmonary dysfunction group (Mann-Whitney test, p = 0.0004). The median AER was 51 (range, 27-98) microg per minute for patients with Injury Severity Score < 18. The positive predictive value for the development of ARDS or pulmonary dysfunction of AER > 130 microg per minute was 85%, with a negative predictive value of 95%. CONCLUSIONS: These data indicate that the capillary leak associated with the subsequent development of pulmonary dysfunction and ARDS can be detected within 8 hours of admission at the patient's bedside, thus providing a means of early identification of patients at greatest risk and allowing for early intervention.

Adolescent↗
PubMed1995

Thromboxane and neutrophil changes following intermittent claudication suggest ischaemia-reperfusion injury.

OBJECTIVES: It has been postulated that ischaemia-reperfusion occurs in intermittent claudication resulting in neutrophil activation and release of soluble mediators, increasing systemic vascular permeability and enhancing atherogenesis. METHODS: We measured neutrophil deformability, plasma thromboxane levels, and urinary microalbumin excretion in 30 male claudicants, and 10 age- and sex-matched controls, before and after exercise to maximum walking distance. Blood was taken from an antecubital vein. RESULTS: There was an increase in urinary microalbumin excretion after exercise in claudicants. Statistically significant increases in the median and 90th percentile transit times (markers of neutrophil deformability) for isolated neutrophils from blood drawn 5 min after exercise in the claudicants were observed with no change in control subjects. Plasma thromboxane concentrations in claudicants increased within 10 min post-exercise. Plasma concentrations in controls were significantly lower throughout the study period. In the claudicant group, a positive correlation between the percentage change in the median transit time for neutrophils, and the percentage change in plasma thromboxane at 60 min post-exercise was found. CONCLUSIONS: The results lend further support to the concept of ischaemia-reperfusion events in patients with intermittent claudication, leading to a systemic increase in vascular permeability as a result of endothelial injury or dysfunction (a crucial step in atherogenesis), associated with thromboxane production and neutrophil activation. We suggest that the above changes may contribute to the increased mortality seen in such patients.

Adult↗
PubMed1994

Microproteinuria predicts the severity of systemic effects of reperfusion injury following infrarenal aortic aneurysm surgery.

Noncardiogenic pulmonary dysfunction can be demonstrated in all patients following elective aortic aneurysm repair and is a cause of postoperative morbidity. Aortic clamping and reperfusion initiate a systemic inflammatory response producing endothelial damage and increases in vascular permeability. In the lung this is manifest as pulmonary edema and in the kidney as detectable increases in urinary protein excretion (microproteinuria). Immunoassay of low-level protein excretion appears to provide an index of the systemic effects of local reperfusion injury and may allow early prediction of complications such as pulmonary edema. Hourly urinary albumin and IgG excretion was measured in 40 patients undergoing infrarenal aortic aneurysm repair and expressed as ratios to urinary creatinine (albumin/creatinine ratio [ACR] and IgG/creatinine ratio [IgGCR]). These were compared to clinical outcome. Pulmonary dysfunction was assessed according to PaO2:FiO2 ratios and chest radiography. Within 180 minutes of beginning surgery all patients had significant increases in ACR and IgGCR. Ten patients who manifested respiratory dysfunction had significantly higher ACRs at 4 hours (median 84.8, 95% confidence intervals, range 47.7 to 136) than patients who made uneventful recoveries (median 16.6, 95% confidence intervals, range 7.9 to 31.7). IgGCR increases paralleled that of ACRs. Differences persisted for 24 hours. Urinary protein excretion rises rapidly during aortic surgery. The degree of increase appears to predict development of pulmonary dysfunction. This simple test may provide a rational basis for evaluation of therapeutic modalities to limit reperfusion injury in these patients.

Aged↗
PubMed1994

Pharmacological reduction of the systemically damaging effects of local ischaemia.

Many patients with intermittent claudication are encouraged to exercise. However, transient exercise-induced muscle ischaemia results in systemic vascular endothelial injury associated with increased vascular permeability manifest as an increase in urinary albumin excretion. Repetitive systemic vascular endothelial injury leads to accelerated atherogenesis and may explain the high cardiovascular mortality rate of claudicants. Oxpentifylline, a haemorheological agent, has recently been shown to prevent vascular endothelial injury in animal models. A double-blind, placebo-controlled, cross-over trial was undertaken to determine the effect of oxpentifylline on exercise-induced systemic vascular endothelial injury in 20 claudicants. Urinary albumin, expressed as a creatinine ratio (ACR), was measured before and 1 and 2 hours after standardised exercise following 1 week treatment with either active drug or placebo. Oxpentifylline reduced the median (range) 1 hour post exercise increase in ACR from 0.35 (-0.46-12.72) to 0.02 (-6.00-14.10) mg/mmol. (p = 0.030, z = 2.2 Wilcoxon rank sign test). These results confirm that local ischaemia is associated with a potentially deleterious systemic effect and that it may be possible to attenuate this pharmacologically. The clinical significance of this is yet to be determined.

Aged↗
PubMed1994

Microalbumin excretion in patients with positive exercise electrocardiogram tests.

Thirty-three subjects underwent exercise electrocardiogram testing, 20 had a history of myocardial infarction and 13 were age-matched volunteers. Exercise electrocardiograms were positive in 15 subjects, negative in 12 and anomalous in six. Urinary microalbumin excretion was measured at rest, 30 and 60 min after exercise. Urinary microalbumin excretion was expressed as the albumin-creatinine ratio in mg.mmol-1. In the positive exercise electrocardiogram group median albumin-creatinine ratio increased from 1.0 mg.mmol-1 (95% CI 0.94-1.49) at rest to 2.0 mg.mmol-1 (95% CI 1.51-3.94) 30 min after exercise, whilst in the negative electrocardiogram group median resting and 30 min post exercise albumin-creatinine ratio values of 0.85 (95% CI 0.53-1.32) and 1.80 (95% CI 0.63-2.32) mg.mmol-1 respectively were not significantly different. These results suggest that exercise-induced myocardial ischaemia is associated with increased urinary microalbumin excretion.

Albuminuria↗
PubMed1994

Generalized vascular permeability and pulmonary function in patients following serious trauma.

It has been suggested that the adult respiratory distress syndrome (ARDS) is a manifestation of a generalized vascular permeability defect. Low-level urinary albumin excretion reflects changes in systemic vascular permeability in a variety of acute inflammatory conditions including trauma. To test the hypothesis that impaired pulmonary function is associated with increased systemic vascular permeability, 44 trauma patients with Injury Severity Scores (ISS) ranging from 9 to 75 were studied over 3 days. Urinary albumin was measured from admission and expressed as the albumin/creatinine ratio (ACR). In 24 mechanically ventilated patients mean inspired oxygen/fraction (FIO2) and mean arterial oxygen tension (PO2) were used to calculate the PO2/FIO2 ratio. For each study day patients were divided into group I, mean FIO2 > 0.5; group II, mean FIO2 < 0.5; and group III, those breathing spontaneously. During the first posttrauma period the log ACR and the PO2/FIO2 ratio were inversely related (r = -0.712; p < 0.001), and the log ACR predicted PO2/FIO2 independent of ISS (p = 0.001). The log mean ACR (SD) for groups I and III were 34.0 (5.6) and 8.7 (2.9) mg/mmol, respectively (Mann Whitney p = 0.013). Following trauma, pulmonary dysfunction is associated with increased vascular permeability in remote organs.

Adolescent↗
PubMed1994

Fresh haemolysis interferes with blocked p-nitrophenylmaltoheptaoside amylase methods.

Two commercial amylase methods which employ p-nitrophenol derivatives of blocked maltoheptaosides suffer from negative interference due to fresh haemolysate. Specimen storage at room temperature, or pre-incubation at 37 degrees C or 57 degrees C removes the effect. Incubation of amylase reagent at 37 degrees C with fresh haemolysate where the final haemoglobin concentration was 0.011 g/L, showed a rapid fall in absorption around 414 nm which became stable after 150 min. Since p-nitrophenol, the product of the amylase reaction, is measured at 405 nm it is concluded that the negative interference from fresh haemolysis is due to the transitory fall in absorption around 405 nm. It is recommended that amylase measurements using this technique, particularly those performed as an emergency, should not be done on haemolysed specimens.

Amylases↗
PubMed1993

Intermittent claudication incites systemic neutrophil activation and increased vascular permeability.

Reperfusion following severe ischaemia incites a systemic response involving neutrophil activation and vascular injury. Recent work suggests that intermittent claudication may also be capable of inducing similar changes, reversible by revascularization. This observation may have implications for the treatment of claudication and explain the high associated cardiovascular mortality. This hypothesis was investigated using an in vivo model. Rats underwent repeated hindlimb stimulation after common iliac artery ligation. Intravital fluorescence microscopy was used to observe postcapillary venules of the tibialis anterior muscle in the hindlimb. This revealed a bilateral increase in leucocyte-endothelial adhesion and vascular permeability to albumin after unilateral subtotal ischaemia and muscle stimulation, associated with increased urinary albumin excretion. These results provide further evidence supporting the association of intermittent claudication with potentially deleterious systemic manifestations.

Animals↗
PubMed1992

Serum c-reactive protein in patients with serious trauma.

Daily serum c-reactive protein (CRP) concentration was monitored in 98 patients (26 female) admitted to the Major Injuries Unit (MIU) at Birmingham Accident Hospital following serious trauma. The mean (SD) increase in CRP concentration for 79 survivors and 19 non-survivors between days 1 and 2 after trauma were 69.5 (74.6) and 111.8 (59.0) mg/l/24 h, respectively (P = < 0.001). By day 4 after trauma the mean serum CRP concentrations for survivors and non-survivors were 150.9 (76.9) and 233.4 (100.8) mg/l (P < 0.001), respectively. Injury severity data were available for 50 patients. The mean (range) injury severity score was 25.2 (4-50), Glasgow coma scale 10.4 (3-15), revised trauma score 6.5 (3.39-7.8) and predicted survival 0.78 (0.02-0.99). Univariate regression analysis of serum CRP on days 1-5 after injury against revised trauma score and injury severity score, revealed an inverse correlation between day 1 serum CRP and Glasgow Coma Score (r = -0.306, P < 0.05), but no correlation with injury severity score or predicted survival on any of the study days. The lack of correlation between serum CRP and injury severity or predicted survival, and the strong association with actual survival, suggests that the acute inflammatory response to serious trauma and subsequent complications, is an important determinant of outcome.

Adolescent↗