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P Gosling

Publications and source records attributed to P Gosling.

At least 19 recordsLinked to original sources
PubMed2006

Microalbuminuria: a marker of endothelial dysfunction in thermal injury.

INTRODUCTION: Systemic endothelial dysfunction (SED) and capillary leak occur following severe burn. SED can be assessed as low-level albuminuria (microalbuminuria) detectable only by sensitive immunoassay. This study compared the magnitude and duration of microalbuminuria with burn surface area and associated aggravating factors. METHODS: Serial urine specimens were collected from 2 to 36 h after injury from 43 adult burn patients with a mean total body surface area (TBSA) of 32% (range 15-68%) and during 44 episodes of wound manipulation within the same period. Urinary albumin was expressed as the albumin/creatinine ratio (ACR, normal <2.3 mg/mmol). RESULTS: Median ACR was highest 2h after injury (12.3 range 1.8-118 mg/mmol) returning to normal within 6 h. Full thickness burns (mean 17%) showed a significant association with ACR between 3 and 7h after burn. ACR was higher for up to 8 h in the presence of inhalation injury, alcohol intoxication or accelerant (p<0.05). ACR rose within 30 min of escharotomy or wound scrubbing (p<0.01). CONCLUSION: Severe burn produces variable SED which recurs with wound manipulation. Inhalation injury, alcohol intoxication and accelerant all showed a stronger association with SED than TBSA. Microalbuminuria provides a means of monitoring microvascular integrity during the early after injury period.

Adolescent↗
PubMed2005

The effects of hydroxyethyl starch compared with gelofusine on activated endothelium and the systemic inflammatory response following aortic aneurysm repair.

OBJECTIVE: To investigate the effect of HES, used as a plasma volume expander, on endothelial cell activation induced by ischaemia-reperfusion in humans. MATERIAL AND METHODS: Forty patients undergoing elective infrarenal aneurysm repair were randomised to receive either gelatine or hydroxyethyl starch solution as plasma expanders. The anaesthetic technique was standardised. All patients received the same crystalloid as per standard protocol. Urine samples and blood samples were collected at various times for assessment of microalbuminuria and von Willebrand factor (vWf) and CRP. RESULTS: The peak C-reactive protein was significantly lower in the patients treated with HES than those treated with gelofusine [142 mg/L (113,196 mg/L) vs 246 mg/L (189,291 mg/L) mg/L, P < 0.01, Mann-Whitney test]. The peak ACR was also significantly lower in the HES treated patients (9.3 mg/mmol vs 23.3 mg/mmol, P < 0.05). The plasma level of vWf was significantly higher in the gelofusine treated patients than those treated with HES [173.5 U/dl Vs 80.5 U/dl, P < 0.001, at 4 hr; 160 U/dl Vs 82.5 U/dl, P < 0.001, at 8 hr; 191 U/dl Vs 100.5 U/dl, P < 0.001, at 12 hr; 209 U/dl Vs 81.0 U/dl, P < 0.001, at 24 hr]. CONCLUSION: HES may damp down the systemic inflammatory response and reduce endothelial cell dysfunction.

Aged↗
PubMed2004

Chronic transcutaneous electrical stimulation of calf muscles improves functional capacity without inducing systemic inflammation in claudicants.

OBJECTIVES: To assess whether electrical stimulation of ischaemic calf muscles in claudicants causes a systemic inflammatory response and to evaluate effects of its chronic application on muscle function and walking ability. DESIGN: Prospective randomised controlled trial of calf muscle stimulation. MATERIALS AND METHODS: Stable claudicants were randomised to receive either active chronic low frequency (6 Hz) motor stimulation (n=15) or, as a control treatment, submotor transcutaneous electrical nerve (TENS) stimulation (n=15) of calf muscles in one leg, 3 x 20 min per day for four weeks. Leucocyte activation was quantified by changes in cell morphology, vascular permeability by urinary albumin:creatinine ratio (ACR), calf muscle function by isometric twitch contractions and walking ability by treadmill performance pre- and post-intervention. RESULTS: Acute active muscle stimulation activated leucocytes less (28% increase) than a standard treadmill test (81% increase) and did not increase ACR. Chronic calf muscle stimulation significantly increased pain-free walking distance by 35 m (95% CI 17, 52, P<0.001) and maximum walking distance by 39 m (95% CI 7, 70, P<0.05) while control treatment had no effect. Active stimulation prevented fatigue of calf muscles during isometric electrically evoked contractions by abolishing the slowing of relaxation that was responsible for loss of force. CONCLUSIONS: Chronic electrical muscle stimulation is an effective treatment for alleviating intermittent claudication which, by targeted activation of a small muscle mass, does not engender a significant systemic inflammatory response.

Aged↗
PubMed2004

Randomized study comparing the effects of hydroxyethyl starch solution with Gelofusine on pulmonary function in patients undergoing abdominal aortic aneurysm surgery.

BACKGROUND: Restoring blood flow to ischaemic tissue can cause lung damage with pulmonary oedema. Hydroxyethyl starch (HES) solution, when used for volume replacement, may modify and reduce the degree of ischaemia-reperfusion injury. We compared the effects of HES solution with those of Gelofusine solution on pulmonary function, microvascular permeability and neutrophil activation in patients undergoing elective infrarenal abdominal aortic aneurysm surgery. METHODS: Forty patients were randomized into two groups. The anaesthetic technique was standardized. Lung function was assessed with the PO(2)/FI(O(2)) ratio, respiratory compliance, chest x-ray and a score for lung injury. Microvascular permeability was determined by measuring microalbuminuria. Neutrophil activation was determined by measurement of plasma elastase. RESULTS: Four hours after surgery, the median (quartile values) PO(2)/FI(O(2)) ratio was 40.3 (37.8, 53.1) kPa for the HES-treated patients compared with 33.9 (31.2, 40.9) kPa for the Gelofusine-treated patients (P<0.01, Mann-Whitney test). The respiratory compliance was 80 (73.5, 80) ml cm(-1) H(2)O in the HES-treated patients compared with 60.1 (50.8, 73.3) ml cm(-1) H(2)O in the Gelofusine-treated patients (P<0.01, Mann-Whitney test). The lung injury score 4 h after surgery was less for the patients treated with HES compared with the patients treated with Gelofusine (0.33 vs 0.71, P=0.01, Wilcoxon rank sum test). Mean (SD) plasma elastase was less in the HES-treated patients on the first postoperative day (1.96 (0.17) vs 2.08 (0.24), P<0.05). The log mean microalbuminuria was less in the HES-treated patients (0.41 vs 0.91 mg mmol(-1), P<0.05). This difference in microvascular permeability was associated with different volumes of colloid required to maintain stable cardiovascular measurements in the two groups of patients studied (3000 vs 3500 ml, P<0.01, Mann-Whitney test). CONCLUSION: Compared with Gelofusine, the perioperative pulmonary function of patients treated with HES after abdominal aortic aneurysm surgery was better.

Aged↗
PubMed2004

Urinary albumin excretion: a predictor of glomerular findings in adults with microscopic haematuria.

BACKGROUND: Microscopic haematuria without proteinuria is a common clinical finding. When urological causes are excluded, usual findings on renal biopsy are IgA nephropathy (which can progress to end-stage renal failure) or thin basement membrane nephropathy (which has an excellent prognosis). A non-invasive test to discriminate between the two would be useful. AIM: To examine the value of measurement of urinary albumin excretion in discriminating glomerular causes of microscopic haematuria in patients without proteinuria on urine dipstick tests. DESIGN: Single-centre retrospective cross-sectional observational study. METHODS: Adult patients who underwent renal biopsy for microscopic haematuria over a 6-year period from January 1994 were identified. Study entry required normal renal function, no proteinuria detected by dipstick, and urinary albumin excretion <300 mg/24 h. Patients with IgA nephropathy had follow-up for a mean of 58 months after biopsy. RESULTS: Of 169 patients fulfilling study criteria, 119 (70%) had normoalbuminuria (<30 mg/24 h); 52 (30%) had microalbuminuria (30-299 mg/24 h). Of those with normoalbuminuria, 106 (89%) had thin basement membrane nephropathy or no glomerular abnormality. Thirteen (11%) had IgA nephropathy, and of 12 of these followed-up for a mean 64 months, none developed overt, dipstick-positive proteinuria. In contrast, 24 (48%) of those with microalbuminuria had IgA nephropathy, and of 22 followed-up for a mean 55 months, five developed overt proteinuria. DISCUSSION: Urinary albumin excretion is an indicator of likely glomerular findings in microscopic haematuria, and may influence whether a renal biopsy is necessary.

Adult↗
PubMed2004

Modulation of the antibody response by Porphyromonas gingivalis and Fusobacterium nucleatum in a mouse model.

Successive immunization of mice with Fusobacterium nucleatum and Porphyromonas gingivalis has been shown to modulate the specific serum IgG responses to these organisms. The aim of this study was to investigate these antibody responses further by examining the IgG subclasses induced as well as the opsonizing properties of the specific antibodies. Serum samples from BALB/c mice immunized with F. nucleatum (gp1-F), P. gingivalis (gp2-P), P. gingivalis followed by F. nucleatum (gp3-PF) F. nucleatum followed by P. gingivalis (gp4-FP) or saline alone (gp5-S) were examined for specific IgG1 (Th2) and IgG2a (Th1) antibody levels using an ELISA and the opsonizing properties measured using a neutrophil chemiluminescence assay. While IgG1 and IgG2a subclasses were induced in all immunized groups, there was a tendency towards an IgG1 response in mice immunized with P. gingivalis alone, while immunization with F. nucleatum followed by P. gingivalis induced significantly higher anti-P. gingivalis IgG2a levels than IgG1. The maximum light output due to neutrophil phagocytosis of P. gingivalis occurred at 10 min using nonopsonized bacteria. Chemiluminescence was reduced using serum-opsonized P. gingivalis and, in particular, sera from P. gingivalis-immunized mice (gp2-P), with maximum responses occurring at 40 min. In contrast, phagocytosis of immune serum-opsonized F. nucleatum demonstrated peak light output at 10 min, while that of F. nucleatum opsonized with sera from saline injected mice (gp5-S) and control nonopsonized bacteria showed peak responses at 40 min. The lowest phagocytic response occurred using gp4-FP serum-opsonized F. nucleatum. In conclusion, the results of the present study have demonstrated a systemic Th1/Th2 response in mice immunized with P. gingivalis and/or F. nucleatum with a trend towards a Th2 response in P. gingivalis-immunized mice and a significantly increased anti-P. gingivalis IgG2a (Th1) response in mice immunized with F. nucleatum prior to P. gingivalis. Further, the inhibition of neutrophil phagocytosis of immune serum-opsonized P. gingivalis was modulated by the presence of anti-F. nucleatum antibodies, while anti-P. gingivalis antibodies induced an inhibitory effect on the phagocytic response to F. nucleatum.

Animals↗
PubMed2003

Salt of the earth or a drop in the ocean? A pathophysiological approach to fluid resuscitation.

The evolved endocrine response after injury leads to sodium, chloride, and water retention at a time when large volumes of sodium containing fluids are given to maintain the circulation and preserve tissue oxygenation. Sodium, chloride, and water are also retained because of increased systemic vascular permeability to plasma proteins, especially albumin, which sequesters fluid in the interstitial space and causes oedema. Excessive fluid and electrolyte retention and interstitial oedema are associated with the systemic inflammatory response syndrome and multiple organ dysfunction, and failure. This review attempts an overview of these processes and addresses the question, "Can manipulation of fluid resuscitation influence the inflammatory response to injury and organ function". Results of randomised controlled prospective clinical studies suggest that limiting the sodium and chloride input and optimal use of synthetic colloids, which are well retained in the vascular space, can reduce the inflammatory response to injury and improve organ function.

Capillary Permeability↗
PubMed2002

Splanchnic oxygenation in patients undergoing abdominal aortic aneurysm repair and volume expansion with eloHAES.

BACKGROUND: Gastric intramucosal pH (pHi), a surrogate marker of splanchnic oxygenation, falls following abdominal aortic aneurysm surgery. AIM: To investigate the effects of volume expansion with hydroxyethyl starch (eloHAES) on splanchnic perfusion compared to another colloid such as gelofusine. PATIENTS AND METHODS: Twenty-two consecutive patients undergoing AAA repair were randomised to receive either eloHAES or gelofusine as plasma expanders. Tissue oxygenation was monitored (10 gelofusine and 12 eloHAES) indirectly by measuring pHi using a nasogastric tonometer. RESULTS: Compared to the eloHAES group, the fall in pHi was significantly greater in the gelofusine group at clamp release (7.29 vs 7.33, P=0.003) and at 4 h following clamp release (7.29 vs 7.33, P=0.03). There was a good inverse correlation between the lowest pHi and the peak serum interleukin-6 (r(s)= -0.47, P=0.03). By multivariate analysis, the only factor that influenced the pHi was the type of colloid used (F=5.54, P=0.005). The eloHAES treated patients required significantly less colloid on the first postoperative day (3175 +/- 175 vs 4065 +/- 269 ml, P=0.01). CONCLUSION: In patients undergoing abdominal aortic aneurysm repair, plasma expansion with eloHAES improves microvascular perfusion and splanchnic oxygenation.

Aged↗
PubMed2001

Early post-traumatic acute respiratory distress syndrome and albumin excretion rate: a prospective evaluation of a 'point-of care' predictive test.

All patients sustaining major trauma exhibit increased capillary permeability, manifested as micro-albuminuria. Urinary albumin excretion rate (AER) measured on intensive care units (ICU) can predict early post-traumatic acute respiratory distress syndrome (ARDS). This prospective study sought to evaluate AER as a practical predictive test for early ARDS. Staff at the participating centres were trained in the use of the Behring Turbitimer and the concept of AER as a predictor of early post-traumatic ARDS. AER was measured every 2 h for the first 24 h, on 54 adult blunt trauma admissions (ISS>/=18). A diagnosis of early acute lung injury (ALI) or ARDS was made using the American-European Consensus Conference criteria. Eleven patients developed ARDS, ten developed ALI, and 23 had no pulmonary dysfunction. The AER was significantly greater in those who developed ARDS 8 and 18 h after admission. The positive predictive value of the test was 64% at 8 h, the negative predictive power 73%. The test was performed most consistently in the middle 10 h of the study period. If intervention had been based on the 8 h data point result, 75% patients who had the test performed and later developed ARDS would have had intervention appropriately. In principle, testing for AER as a predictor of post-traumatic ARDS on ICU is feasible, however, this study has underlined the challenges of introducing new concepts into the ICU environment.

Albuminuria↗
PubMed2000

Microalbuminuria following anaphylaxis with general anaesthesia.

Microalbuminuria is increasingly recognized as a marker of pathologies that cause acute systemic capillary leak. We report a case of an anaphylactic reaction to general anaesthesia involving cardiac arrest. In this case the urinary excretion of albumin following resuscitation suggests that severe anaphylaxis is another condition for which microalbuminuria is a sensitive monitor.

Adolescent↗
PubMed1999

Randomized trial of hydroxyethyl starch versus gelatine for trauma resuscitation.

BACKGROUND: Previous studies have demonstrated the rapid increase in systemic capillary permeability after blunt trauma and its association with poor outcome. There are theoretical advantages in resuscitation with colloid fluids, which are well retained in the vascular compartment during times of capillary leak. The aim of this study was to compare the effects of posttrauma resuscitation with hydroxyethyl starch (HES) (molecular mass, 250 kDa) or gelatine (molecular mass, 30 kDa), the hypothesis being that HES would reduce capillary leak. METHODS: Forty-five patients suffering blunt trauma were randomized on admission to receive either gelatine (Gelofusine) (n = 21) or HES (Pentaspan) (n = 24) for the first 24 hours, after which the choice of fluid was at the discretion of the clinician. The mean Injury Severity Score for the HES and gelatine groups were 20.0 (range, 9-41) and 18.1 (range, 9-32), respectively (p = 0.43). Capillary permeability was assessed by urine albumin excretion rate for the first 24 hours. For 5 days the daily mean P(O2)/F(IO2) ratio, serum C-reactive protein, hemoglobin, white cell and platelet counts, prothrombin, and activated partial thromboplastin time were recorded. RESULTS: Capillary permeability was lower in HES-treated patients during the first 24 hours. Log mean (95% confidence interval) albumin excretion rate for gelatine and HES groups at 6 hours were 117.5 (84.9) and 46.8 (24.3) microg/min (p = 0.011), at 12 hours were 54.9 (30.0) and 17.2 (7.6) microg/min (p = 0.001), and at 24 hours were 50.5 (23.4) and 23.6 (16.3) microg/min (p = 0.030), respectively. The mean (95% confidence interval) P(O2)/F(IO2) ratio for the HES and gelatine groups 48 hours after admission were 324 (44) and 267 (43) mm Hg, respectively (p = 0.03). The mean (95% confidence interval) serum C-reactive protein in the HES and gelatine groups 24 hours after admission were 72.4 (19.2) and 105.7 (30.1) mg/L, respectively (p = 0.03). There were no significant differences in any of the hematologic parameters during the first 48 hours. CONCLUSION: The results suggest that compared with gelatine, resuscitation with HES reduces posttrauma capillary leak.

Adolescent↗