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Biomedical subjects

A R Webb

Publications and source records attributed to A R Webb.

At least 37 records · Page 2Linked to original sources
PubMed1994

Intra-operative gut mucosal hypoperfusion is associated with increased post-operative complications and cost.

OBJECTIVES: To determine CO and gastric mucosal perfusion in patients during elective major surgery; to seek a relationship with subsequent outcome. DESIGN: Prospective descriptive study. SETTING: University hospital. PATIENTS: 51 patients undergoing elective major surgery of an anticipated duration of greater than 2 h who were at risk of developing gut mucosal hypoperfusion and postoperative organ failure. MEASUREMENTS AND RESULTS: CO was determined by oesophageal Doppler measurement of aortic blood flow. Gastric mucosal perfusion was determined by tonometric assessment of gastric mucosal pH (pHi). Blood pressure and urine flow were measured. At the end of surgery no patients were oliguric or hypotensive. Post-operatively morbidity, mortality, duration and cost of stay in the ITU and hospital were assessed. There were 32 patients with evidence of gastric mucosal ischaemia at the end of surgery (pHi < 7.32) despite maintenance of CO. This group of patients spent a mean of 4.7 (range 0-33) days in the ITU, 14 developed major complications (7 with multiple organ failure [MOF] and 6 died. In 19 patients gut mucosal perfusion was maintained during surgery (pHi > or = 7.32); these patients demonstrated an increase in CO of 48.4% (95% confidence interval 21.3 -75.6) and spent a mean of 1.0 (range 0-4) days in the ITU. Only one developed a major complication and none died. The total cost of post-operative care for the 51 patients was estimated at pounds 356650. Mean cost per patient in the low pHi group was significantly greater at pounds 8845 (range pounds 600--pounds 42,700) compared to pounds 3874 (range pounds 2,600--pounds 9,600) in the normal pHi group. The total.cost of post-operative care for the 7 patients who developed MOF was pounds 171,450 i.e. 48% of the total cost. CONCLUSION: A low gastric pHi measured during the intraoperative period in a group of patients undergoing major (mainly cardiovascular) surgery is associated with increased post-operative complications and cost.

Adult↗
PubMed1994

Low intramucosal pH is associated with failure to acidify the gastric lumen in response to pentagastrin.

OBJECTIVE: To determine if low gastric intramucosal pH is associated with impaired secretion of gastric acid after pentagastrin stimulation. DESIGN: Prospective study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: 20 patients requiring mechanical ventilation. INTERVENTIONS: All patients with a gastric luminal pH > 4 were given pentagastrin 6 micrograms/kg s.c. to stimulate gastric acid secretion and the response assessed by further measurements of gastric luminal pH. MEASUREMENTS AND RESULTS: Gastric intramucosal pH (pHi) and luminal pH (pHL) were measured. Patients were divided into two groups on the basis of a low or normal pHi (A value of 7.35 was taken as the lower limit of normal). Patients (n = 6) with normal pHi (7.40 +/- 0.05 [mean +/- SD]) and a luminal pH > 4 (5.65 +/- 1.25) all had a decrease in pHL in response to pentagastrin (decrease in pHL 4.02 +/- 1.52). Of the patients (n = 7) with low pHi (7.2 +/- 0.13) and a pHL > 4 (6.51 +/- 0.48) only one responded to pentagastrin (decrease in pHL for this group 0.93 +/- 1.86). Patients with a pHL < 4 (2.4 +/- 0.71) were not given pentagastrin (n = 7). CONCLUSION: Some critically ill patients with low gastric intramucosal pH appear to have an impaired ability to acidify the gastric lumen in response to pentagastrin.

Achlorhydria↗
PubMed1994

The effect of hydroxyethyl starch and other plasma volume substitutes on endothelial cell activation; an in vitro study.

OBJECTIVE: To study the effect of medium molecular weight hydroxyethyl starches on endothelial cell and neutrophil activation in vitro. SETTING: Laboratory analysis. METHODS: The effects of albumin and hydroxyethyl starch on the neutrophil adhesion molecule (CD11bCD18), with and without lipopolysaccharide stimulation, were studied in whole blood. E-selectin expression on human umbilical vein endothelial cells was stimulated with lipopolysaccharide alone and in the presence of either albumin or hydroxyethyl starch. The effect of albumin and hydroxyethyl starches on rapid endothelial cell activation was studied using von Willebrand factor release as a marker. MEASUREMENTS AND RESULTS: Hydroxyethyl starches but not albumin inhibited stimulated vWF release in a dose dependent manner. No effect was seen on endothelial E-selectin or neutrophil CD11bCD18 expression. CONCLUSIONS: these results suggest a possible beneficial role of hydroxyethyl starches in the inhibition of endothelial activation thus preventing neutrophil adhesion during sepsis syndrome.

Cell Adhesion↗
PubMed1994

Phaeochromocytoma presenting as acute hyperamylasaemia and multiple organ failure.

Phaeochromocytoma may present in many different ways. We report an unusual presentation of phaeochromocytoma in a man with hyperamylasaemia and multiple organ failure thought to be due to acute relapsing pancreatitis. Abdominal ultrasound and computerised tomography (CT) examinations revealed a mass at the tail of the pancreas. Fine needle biopsy of the mass precipitated headache, intense vasoconstriction and labile blood pressure. He proceeded to laparotomy, at which an 8 x 9 cm mass was found to be replacing the left adrenal gland. Histological examination revealed a phaeochromocytoma. This case illustrates that hyperamylasaemia and multiple organ failure may be unusual presentations of phaeochromocytoma and may be unusual presentations of phaeochromocytoma and phaeochromocytoma should be considered in the differential diagnosis of a peripancreatic mass found by ultrasound or CT.

Acute Disease↗
PubMed1994

Epidermis and serum protect retinol but not retinyl esters from sunlight-induced photodegradation.

Sunlight-induced photodegradation of retinyl esters and retinol in human skin, blood and cultured keratinocytes was investigated. Using high-performance liquid chromatography with an extraction method that avoided saponification, the analysis of human foreskin (Caucasian) showed that levels of retinyl esters and retinol were approximately 3.5 and 5.0 times higher, respectively, in the epidermis than in the dermis. Upon irradiation by sunlight, a significant reduction in epidermal retinyl esters was observed in both summer and winter. However, epidermal retinol, dermal retinol and dermal retinyl esters did not show statistically significant reductions. When serum from volunteers who had taken a large dose of retinyl palmitate to elevate serum retinyl esters was exposed to sunlight, the retinyl esters in the serum rapidly disappeared after 10 min of exposure--similar to the photodegradation seen for retinyl palmitate in an organic solvent. While retinol in an organic solvent rapidly photodegraded similar to serum retinyl palmitate, serum retinol slowly declined upon sunlight irradiation. When cultured keratinocytes that took-up 3H-retinol and thereafter contained 3H-retinyl esters and 3H-retinol were exposed to sunlight, 80% of the 3H-retinyl esters disappeared upon sunlight irradiation whereas only about 20% of the 3H-retinol did so. These results suggest that the epidermis, serum and keratinocytes selectively protect retinol from sunlight-induced photodegradation. It is most likely that serum retinol-binding protein and cellular retinol-binding protein protect retinol, a vital epithelial growth factor, from photodegradation.

Blood↗
PubMed1993

The rational administration of colloids.

The safe administration of i.v. fluids is one of the most significant advances in the care of critically ill patients this century. However, despite advances in the monitoring of cardiovascular variables, the questions of what? when? and how much? remain areas of enormous controversy. Ironically as the choice of i.v. fluids becomes greater and the monitoring more sophisticated the controversy grows. This article will concentrate on the diagnosis of hypovolaemia, the consequences of hypovolaemia and the rational use of i.v. fluids, particularly colloids, to treat it.

Blood Volume↗
PubMed1993

Postoperative multiple organ dysfunction syndrome associated with gut mucosal hypoperfusion, increased neutrophil degranulation and C1-esterase inhibitor depletion.

We have examined the relationship between gut mucosal perfusion, as determined by gastric intramucosal pH (pHi), changes in plasma neutrophil elastase concentrations and components of the contact system during elective major surgery and related these findings to patient outcome. Of the 26 patients studied, 16 developed gut mucosal hypoperfusion (pHi < 7.32) by the end of surgery; four of these developed multiple organ dysfunction syndrome; three of these died. In this group there was a significant increase in neutrophil elastase (P < 0.005) and significant reductions in plasma components of the contact system from immediately before surgery to 24 h later. Ten patients maintained gut mucosal perfusion (pHi > or = 7.32); none of these developed life threatening complications. In this group there was no significant increase in neutrophil elastase and, although there were significant reductions in some plasma components of the contact system, concentrations of C1-esterase inhibitor (the main inhibitor of the contact system) were not significantly reduced. We conclude that gut mucosal hypoperfusion, neutrophil degranulation and activation of the contact system to the extent that C1-esterase inhibitor becomes depleted are associated with a poor outcome after major surgery.

Adult↗
PubMed1993

The role of endotoxin immunity, neutrophil degranulation and contact activation in the pathogenesis of post-operative organ dysfunction.

Gut mucosal hypoperfusion is associated with a poor outcome following major surgery but the pathogenetic mechanisms remain poorly understood. We have examined the relationship between gut mucosal hypoperfusion, endotoxin core antibodies (EndoCAb), neutrophil elastase alpha-1 antitrypsin complexes (NE) and components of the contact system during elective major surgery. Of the 26 patients studied 16 developed gut mucosal hypoperfusion (pHi < 7.32) by the end of surgery; of these four developed multiple organ failure (MOF) and three subsequently died. In this group there was a significant rise in NE (P < 0.005) and significant reductions in components of the contact system (factor XII, antithrombin III, prekallikrein and C1-inhibitor; P < 0.001) from immediately before surgery to 24 h later. Ten patients maintained gut mucosal perfusion (pHi > or = 7.32); none of these developed life threatening complications. In this group there was no significant increase in NE and, although there were significant reductions in some components of the contact system (P < 0.01), levels of C1-INH were not reduced. All patients demonstrated a significant reduction in both IgG and IgM EndoCAbs (P < or = 0.005) indicating exposure to endotoxin. However, the group that maintained gut mucosal perfusion had significantly higher IgG EndoCAb levels at baseline and 24 h (P < or = 0.005). These data suggest that all patients were exposed to endotoxin and that high levels of anti-endotoxin antibodies may contribute to the prevention of endotoxin-induced contact activation, neutrophil degranulation and gut mucosal hypoperfusion occurring during major surgery and thus reduce the likelihood of the development of post-operative MOF.

Adult↗
PubMed1992

A narrow range, medium molecular weight pentastarch reduces structural organ damage in a hyperdynamic porcine model of sepsis.

OBJECTIVE: to compare diafiltered 6% pentastarch (Pentafraction--PDP, MWn 120,000 and MWw 280,000) and native pentastarch (Pentaspan--PSP, MWn 63,000 and MWw 264,000 dalton) in a porcine model of faecal peritonitis. DESIGN: Randomised prospective study in 12 adolescent pigs. INTERVENTIONS: Prior to infection the study solution was infused to increase Qt by 25%. Thereafter adjustments in infusion rate were made (up to 1 l/h) in an attempt to maintain Qt at 25% above baseline values. MEASUREMENTS AND RESULTS: Animals were sacrificed at 8 h. Tissue was excised from the right lobe of liver and from the right lung and fixed for later electron microscopy and digital morphometric analysis. Patent sinusoidal lumen was significantly greater in group PDP compared to PSP (11.3% +/- 2.3% of liver tissue versus 4.8% +/- 1.1%, p < 0.05) and this was accounted for by a significantly lower proportion of sinusoidal lumen occluded with white cells (2.1% +/- 0.6% versus 6.6% +/- 1.9%, p < 0.05). Similarly, patent capillary represented a significantly higher proportion of lung tissue for group PDP versus PSP (26.2% +/- 1.9% versus 18.5% +/- 2.7%, p < 0.05). The arithmetic mean alveolar capillary barrier thickness was significantly greater in group PSP than in group PDP (4.3 +/- 0.3 microns versus 2.5 +/- 0.3 microns, p < 0.01). CONCLUSIONS: The molecular weight profile of Pentafraction was associated with less structural organ damage including less tissue oedema and less white cell occlusion.

Biopsy↗
PubMed1992

An evaluation of the heat and moisture exchange performance of four ventilator circuit filters.

OBJECTIVE: To compare the heat and moisture exchange efficiency of 4 commonly used ventilator circuit filters--DAR Hygroster (DHS), DAR Hygobac (DHC), Pall Ultipor BB50 (PUBC) and Intersurgical filtatherm (IFT). DESIGN: Prospective randomized study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS AND PARTICIPANTS: 80 patients requiring post-operative mechanical ventilation were entered into the study. A total of 40 patients were studied after 1 h and 40 after 24 h. Due to technical errors 6 of the 1 h studies and 2 of the 24 h studies were excluded from analysis. INTERVENTIONS: Mean wet and dry ceramic-platinum thermal probes were inserted in the inspiratory side of a device which separated inspiratory and expiratory gas flows on the patient side of the ventilator circuit filter. Humidification efficiency was calculated with reference to these wet and dry bulb temperatures. Tracheal temperature was measured by a similar thermal probe in the tracheal tube. MEASUREMENTS AND RESULTS: Absolute humidity was greatest in group DHS (30.4 +/- 3.5 versus 22.9 +/- 1.5 mg/l at 1 h and 27.3 +/- 3.5 versus 20.7 +/- 2.4 mg/l at 24 h). The differences in absolute humidity reached statistical significance as follows: p = 0.0001 for DHS versus all others at 1 h and for DHS and DHC versus PUBC and IFT at 24 h. CONCLUSION: Better humidification capabilities were obtained with groups DHS and DHC than PUBC and IFT.

Aged↗
PubMed1991

The effects of dobutamine, dopexamine and fluid on hepatic histological responses to porcine faecal peritonitis.

We studied the effects of two catecholamines with differing receptor profiles on hepatic blood flow and hepatic structure in a porcine model of faecal peritonitis. We treated animals with dopexamine (group Dp) or dobutamine (group Db) and fluid, or fluid alone as a control, to achieve a 25% increase in Qt from baseline values. After the induction of faecal peritonitis the increased Qt was maintained throughout the 8 h study period by adjustment of the fluid infusion rate. The dose of catecholamines remained constant. Hepatic blood flow was correspondingly maintained at above baseline values throughout the study. Post-mortem liver biopsy specimens were analysed from experimental animals and 5 sham animals who had not been instrumented or infected. In experimental animals there was a reduction in sinusoidal patency between sham and group Dp (76% of total sinusoid vs 51%, p less than 0.05) and group Dp and control (51% vs 33%, p less than 0.05) or groups Dp and Db (51% vs 34%, p less than 0.05) animals. This was accounted for by an increase in sinusoidal leukocytes and endothelial swelling. In addition to the changes noted above there was marked hepatocellular destruction in group Db. We conclude that maintenance of organ blood flow does not guarantee structural integrity in the sepsis syndrome and hepatocellular damage was greater in group Db than group Dp or control.

Adrenergic Agonists↗
PubMed1991

Advantages of a narrow-range, medium molecular weight hydroxyethyl starch for volume maintenance in a porcine model of fecal peritonitis.

OBJECTIVE: To compare the effectiveness of two hydroxyethyl starch solutions of different molecular weight ranges for volume maintenance in a porcine model of fecal peritonitis. DESIGN: Randomized prospective trial. SETTING: Laboratory investigation. SUBJECTS: Adolescent female pigs weighing approximately 30 kg. INTERVENTIONS: We compared diafiltered 6% pentastarch with 6% high molecular weight hetastarch for volume maintenance in a porcine model of fecal peritonitis. The number average molecular weight of pentastarch is higher than hetastarch, although the weight average molecular weight is lower, i.e., a narrow range of medium weight molecules. The infusion rate of each agent was adjusted to maintain baseline arterial Hct for less than or equal to 7 hr after instrumentation and induction of fecal peritonitis. MAIN OUTCOME MEASUREMENTS: The volume of fluid required to maintain arterial Hct was compared along with comparisons of hemodynamic and histologic responses associated with the two agents. RESULTS: Significantly less pentastarch was required to prevent hemoconcentration than hetastarch (109 +/- 22.8 vs. 150 +/- 10.3 mL/kg; p less than .05) while hemodynamics, colloid osmotic pressure, and oxygen transport responses were similar. Capillary patency was greater (21.99 +/- 3.68 vs. 10.09 +/- 1.17%; p less than .05) and mean alveolar capillary barrier thickness was less (2.36 +/- 0.13 vs. 3.06 +/- 0.17 microns; p less than .05) with pentastarch than with hetastarch, as judged by electron microscopy. CONCLUSIONS: These data suggest that pentastarch is better retained in the circulation in capillary leak syndromes compared with hetastarch.

Animals↗
PubMed1991

Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.

OBJECTIVES: To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. SETTING: Medical school laboratory. SUBJECTS: Healthy volunteers. INTERVENTIONS: Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. MEASUREMENTS AND MAIN RESULTS: Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. CONCLUSIONS: Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.

Adrenergic beta-Antagonists↗
PubMed1990

An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston.

We investigated the vitamin D status of a Caucasian elderly population in a long-term-care facility in Boston. Comparison was made with a group of free-living elderly people. The sunlight exposure of residents was monitored and its effect on the serum concentrations of 25-hydroxyvitamin D [25(OH)D] was compared with contributions from diet and multivitamins. Seasonal changes in serum 25(OH)D concentrations caused by sunlight exposure were greatest in the free-living subjects and declined in magnitude as the mobility of the volunteers decreased. Diet failed to provide an adequate amount of vitamin D for volunteers who had minimal outdoor activity. Use of a multivitamin supplement containing 10 micrograms (400 IU) vitamin D maintained serum 25(OH)D concentrations greater than 37.5 nmol/L.

Activities of Daily Living↗