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Biomedical subjects

A C Windsor

Publications and source records attributed to A C Windsor.

At least 37 records · Page 2Linked to original sources
PubMed1995

Circulating ICAM-1 is increased in septic shock.

Adhesion molecules play a critical role in the interaction of circulating neutrophils with vascular endothelium during inflammation. Increased quantities of soluble, circulating intercellular adhesion molecule-1 (cICAM-1) are present in various inflammatory conditions. The purpose of this investigation was to measure cICAM-1 levels in septic adults, as well as to examine the relationship between this potential marker of endothelial-cell activation and the consequences of sepsis (i.e., multiple organ failure and death). Using a sandwich-type enzyme-linked immunosorbent assay (ELISA), we measured cICAM-1 in blood samples obtained within 12 h of admission to an intensive care unit (ICU) for sepsis and other conditions. We found cICAM-1 levels to be increased in 25 septic patients (1,259 +/- 159 ng/ml, mean +/- SEM) as compared with 12 healthy volunteers (355 +/- 41 ng/ml, p < 0.0001) and four ICU patients without systemic inflammatory response syndrome (SIRS) (585 +/- 76 ng/ml, p < 0.001). Twenty-five patients with SIRS but no evidence of causative infection also had elevated levels of cICAM-1 (937 +/- 144 ng/ml, p = 0.12 versus sepsis). Serial measurements over the first week of sepsis demonstrated persistent elevation in most patients. Day 1 cICAM-1 levels were higher (p = 0.017, ANOVA) in 16 patients with septic shock than in seven with severe sepsis and two with sepsis but without hypotension or hypoperfusion. There was a positive correlation (r = 0.50, p = 0.009) between Day-1 cICAM-1 measurements and severity of shock as determined by the presence of hypotension and vasopressor use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A dual-binding antibody to E- and L-selectin attenuates sepsis-induced lung injury.

Many studies indicate a pivotal role for neutrophil adhesion in sepsis-associated lung injury. Neutrophil adhesion to endothelium depends on activation and expression of selectin and integrin adhesion receptors. We studied the effects of pretreatment with a dual-binding porcine anti-E- and anti-L-selectin monoclonal antibody (EL-246) on a porcine model of sepsis-induced lung injury. Four groups were studied for 5 h. Group 1 (control animals) received intravenous saline only. Group 2 (septic) received a 1-h infusion of Pseudomonas aeruginosa. Group 3 (EL-246 pretreatment) received EL-246 (1 mg/kg) prior to Pseudomonas infusion. Group 4 (EL-246 controls) received EL-246 infusion only. Group 2 animals showed rapid, significant decline in arterial pH and oxygen tension whereas, in Group 3, physiologic deterioration was significantly attenuated. Bronchoalveolar lavage at 5 h showed a significant increase in neutrophil count and protein content in Group 2. Group 3, however, showed no significant differences in these parameters compared with control animals. Despite severe neutropenia, lung myeloperoxidase content at 5 h was significantly reduced in Group 3 compared with Group 2. There was no significant difference in pulmonary and systemic hemodynamics between Groups 2 and 3. Group 4 animals exhibited a transient neutropenia, but otherwise no other differences in measured parameters were found compared with Group 1 control animals. In conclusion, EL-246 significantly reduced neutrophil accumulation in lung and attenuated sepsis-induced lung injury, but failed to attenuate deranged pulmonary and systemic hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Delayed tumor necrosis factor alpha blockade attenuates pulmonary dysfunction and metabolic acidosis associated with experimental gram-negative sepsis.

OBJECTIVE: To ascertain the effect of delayed tumor necrosis factor alpha (TNF-alpha) on the evolution of systemic and pulmonary injury after the onset of sepsis. DESIGN: Prospective controlled trial. INTERVENTION: Anesthetized swine were made septic with a 1-hour infusion of live Pseudomonas aeruginosa, following which a treatment group received an infusion of anti-TNF-alpha monoclonal antibody (5 mg/kg). Control animals received 0.9% saline. RESULTS: Delayed anti-TNF-alpha treatment had no effect on septic pulmonary hypertension or decline in cardiac output. Late recovery in systemic arterial hypotension was associated with a reversal of arterial acidosis (P < .05 by t test and analysis of variance with Tukey's Studentized Range Test) compared with unprotected septic animals. Septic animals had a significant increase in mean (+/- SEM) plasma lactate levels at 5 hours compared with baseline values (3.8 +/- 0.7 vs 2 +/- 0.4, P < .05), but remained unchanged from baseline following anti-TNF-alpha treatment (1.5 +/- 0.1 vs 1.6 +/- 0.2, not significant). Characteristic septic neutropenia was dramatically reversed by anti-TNF-alpha treatment and was associated with downregulation (P < .05 by t test and analysis of variance) of polymorphonuclear neutrophil (PMN) leukocyte CD18 adhesion receptors and reduction (P < .05 by t test and analysis of variance) in lung PMN sequestration measured by myeloperoxidase activity. The mean (+/- SEM) decrease in bronchoalveolar lavage protein indicated an attenuated permeability injury in anti-TNF-alpha animals (septic animals at 5 hours compared with baseline value, 1044 +/- 270 vs 149 +/- 28 micrograms/mL; control animals at 5 hours compared with baseline value, 217 +/- 83 vs 129 +/- 19 micrograms/mL; P < .05 by t test and analysis of variance). CONCLUSIONS: These data show that delayed anti-TNF-alpha treatment reversed metabolic acidosis associated with sepsis. Furthermore, anti-TNF-alpha treatment reversed septic neutropenia, reduced PMN sequestration, and was associated with attenuated lung injury in a model of fulminant sepsis. This supports evidence of PMN-mediated tissue injury in sepsis and suggests mechanisms for potential therapeutic benefit of anti-TNF-alpha treatment in clinical practice.

Acidosis, Lactic↗
PubMed1994

Beneficial cardiopulmonary effects of pentoxifylline in experimental sepsis are lost once septic shock is established.

OBJECTIVE: To determine the effects of pretreatment and posttreatment with pentoxifylline in a porcine model of gram-negative sepsis. DESIGN: Nonrandomized controlled trial. STUDY SUBJECTS: Young Yorkshire swine. INTERVENTIONS: Six groups of ventilated swine were studied for 5 hours. Group 1 swine (control, n = 8) received saline solution only. Group 2 swine (sepsis, n = 8) received a 1-hour infusion of Pseudomonas aeruginosa. Groups 3, 4, and 5 swine received the P aeruginosa infusion and a 20 mg/kg bolus followed by a 6 mg/kg per hour infusion of pentoxifylline. Group 3 swine (n = 6) received pentoxifylline prior to the onset of sepsis; group 4 swine (n = 6) received pentoxifylline at 1 hour and group 5 swine (n = 4) at 2 hours after the onset of the P aeruginosa infusion. Group 6 swine (control pentoxifylline, n = 3) received pentoxifylline only. OUTCOME MEASURES: Hemodynamic variables, neutrophil counts and CD18 expression, tumor necrosis factor activity, and arterial blood gases were measured hourly. Bronchoalveolar lavage was performed at 0 and 5 hours to measure neutrophil and protein content. RESULTS: All variables remained unchanged in the control and control pentoxifylline groups. Both pretreatment and posttreatment with pentoxifylline significantly attenuated lung injury and improved arterial PaO2. The cardiac index was significantly improved by administration of pentoxifylline in groups 3 and 4. Administration of pentoxifylline to group 5 animals in established septic shock caused uncontrolled, fatal systemic hypotension in two of the four animals. Plasma tumor necrosis factor activity, blood polymorphonuclear leukocyte counts, and CD18 expression were unaffected by the administration of pentoxifylline. CONCLUSIONS: Pentoxifylline protects against pulmonary and systemic hemodynamic derangements in fulminant sepsis and protects against pulmonary dysfunction. Pentoxifylline has a "therapeutic window" when given in established sepsis; if administration is delayed until overt septic shock occurs, it may then have deleterious effects.

Animals↗
PubMed1994

Multi-agent therapy in the treatment of sepsis-induced microvascular injury.

Cyclo-oxygenase inhibition (with ibuprofen) combined with histamine (H1, H2) receptor antagonism (with diphenhydramine and cimetidine) attenuates microvascular leak injury in sepsis syndromes. Ibuprofen reduces microvascular injury by limiting oxygen radical production by neutrophils. Histamine is known to inhibit this oxygen radical production, an effect antagonized by cimetidine. In the present study neutrophils isolated from pigs made septic with Pseudomonas organisms exhibited a significant (P < 0.05) increase in the production of the oxygen radicals, superoxide anion (O2-, 133 per cent) and hypochlorous acid (HOCl, 38 per cent). Ibuprofen used alone attenuated this sepsis-stimulated overproduction. Addition of the antihistamines cimetidine and diphenhydramine produced a significant increase in oxygen radical production (P < 0.05), by 122 per cent (O2-) and 47 per cent (HOCl), equivalent to that in untreated septic animals. This coincided with a significant deterioration in pulmonary compliance (P < 0.05) compared with that found in control animals and those treated with ibuprofen alone, and a significant accumulation of extravascular lung water (P < 0.05) at 240 and 300 min versus baseline. Histamine receptor antagonism may inadvertently enhance microvascular injury in sepsis.

Animals↗
PubMed1994

Outbreak of infection with penicillin-resistant Streptococcus pneumoniae in a hospital for the elderly.

A penicillin- and trimethoprim-resistant strain of Streptococcus pneumoniae serotype 9 was isolated from sputum, pleural effusion fluid or blood collected from 10 patients with lower respiratory tract infection on three separate wards in a hospital for the elderly over a 3-week period in February, 1993. Eight of the 10 infections were hospital-acquired. Following the cessation of new admissions to wards with infected patients, and a change of antibiotic policy for the treatment of lower respiratory tract infections, there were no new isolates. The outbreak probably resulted from failure to promptly identify, and manage appropriately infection in the index case.

Aged↗
PubMed1994

Differential activation of alveolar, pulmonary arterial, and systemic arterial neutrophils demonstrates the existence of distinct neutrophil subpopulations in experimental sepsis.

Neutrophils (PMNs) are considered key cellular mediators of sepsis induced acute lung injury. PMN activation is manifest by increased beta 2 integrin expression and enhanced superoxide radical (O2-) generation. What is unclear is at which anatomical sites PMNs are activated and at which sites they release O2- and mediate lung injury. In this study we compared alveolar (ALV), systemic arterial (SA), and pulmonary arterial (PA) PMNs CD18 receptor expression, measured by fluorescent immunophenotyping and, O2- generation, measured by reduction of ferricytochrome C, in septic swine. Swine were anesthetized and ventilated, and given a 1-h infusion of live Pseudomonas aeruginosa. PA, SA, and ALV PMNs were isolated at 0 and 5 h. ALV PMNs O2- was reduced compared to SA blood PMNs O2- at 5 h, (AIV 5 h 23.6 +/- 3 vs. SA 0 h 34.3 +/- 5, p < .05). SA PMNs O2- generation was also significantly reduced compared to PA PMNs at 5 h (PA 5 h 21 +/- 2.5 vs. SA 5 h 16.9 +/- 2.6, p < .05). Alv PMNs expressed significantly greater CD18 receptor levels than SA blood PMNs at 5 h (AIV PMNs 5 h, 76 +/- 6 vs. SA PMNs 5 h 51 +/- 3, p < .05), however, PA PMNs CD18 receptor levels were not significantly different from SA PMNs levels at 5 h. These data corroborate a dissociation between two PMN functions in sepsis. O2- generation was reduced across the lung and following migration. However, alveolar PMNs had significantly upregulated CD18 expression compared to PMNs in PA and SA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Ultrasound scanning of the acute abdomen by surgeons in training.

Ultrasound is widely used in the investigation of abdominal symptoms. Its increasing popularity may lead to pressure on radiological services, diagnostic delay and prolonged hospital stay. Immediate imaging performed by radiologists can contribute useful information in acute emergencies. This study assessed the accuracy and value of abdominal ultrasonography when carried out by admitting surgeons. Three surgical registrars were first instructed for two half days by a consultant radiologist. Patients with acute symptoms were scanned at the time of initial presentation using an Aloka SSD-620 scanner with 3.5 and 5 MHz probes. A total of 205 scans was performed--124 of the upper and 81 of the lower abdomen. Immediate ultrasound provided information that contributed to the establishment or refutal of a diagnosis in 138 patients (67.3%), predominantly by confirming or excluding hepatobiliary disease, tubo-ovarian pathology or aortic aneurysms and in blunt abdominal trauma. The diagnosis was altered in a small proportion (7.8%). Scanning proved unhelpful in 62 patients and misleading in five. Findings concurred with those of a radiologist in 86% of the 139 patients subsequently scanned. Abdominal ultrasound is a useful tool in the hands of surgeons dealing with emergencies and may occasionally provide vital information. If access to radiological facilities is delayed, ultrasound by the admitting surgeon could lead to improved patient management and cost savings.

Abdomen, Acute↗
PubMed1993

Role of the neutrophil in adult respiratory distress syndrome.

Adult respiratory distress syndrome (ARDS) remains a significant cause of morbidity and mortality in surgical practice. Despite the continued advance of surgical technique and therapy, the mainstay of treatment of ARDS remains supportive. In the past decade cytokines have been found to be primary chemical mediators of the host response to inflammatory disease. The polymorphonuclear leucocyte has also emerged as a possible cellular mediator of the end-organ damage that characterizes these inflammatory processes. The role of the neutrophil as the primary cellular mediator of alveolar capillary membrane injury in ARDS remains controversial. This article reviews the relevant current literature and considers the implications of the prevailing evidence on future management of this syndrome.

Cell Movement↗
PubMed1993

Long-term circulatory access via a peripheral implantable port.

The use of a novel indwelling central venous catheter system is described which combines the safety of peripheral venous catheter placement with a novel electromagnetic locator device for guidance of the catheter tip into the correct position. This locator system obviates the need for radiological screening or chest radiography for checking catheter placement. Fifty-one patients were studied prospectively and all were successfully cannulated. An infection rate of 0.29 per 1000 catheter-days was seen with a mean system life of 220 (range 15-510) days. The new port has a lower infection rate than other commonly used systems and eliminates complications such as pneumothorax and puncture of major arteries.

Adult↗
PubMed1993

Acute lung injury: what have we learned from animal models?

In 1950, Carl John Wiggers, philosopher and physiologist, wrote, "Reactions to definite types of stimulation may be observed or recorded, and concealed phenomena may be revealed by the use of apparatus that transforms them into forms that are recognizable by human senses. But complete understanding of physiological reactions often necessitates extensive operative procedures and sometimes the ultimate sacrifice of life. For this reason experimentation on animals is indispensable." Acute lung injury is still a significant cause of death in the developed world, and modern pharmacology and intensive care have failed to alter the clinical course of this complex condition. In the past decade, there was an explosion in understanding of the pathophysiology of acute lung injury, and with this has come the development of a new generation of agents that may provide a tool with which to combat this disorder. Use of animal model systems led to this greater understanding and is currently at the heart of evaluating the new therapeutic agents. This review briefly addresses the contribution animal model systems have made to what appear to be a watershed in attempts to obviate the effects of this mortal condition.

Acute Disease↗
PubMed1993

Combined ibuprofen and monoclonal antibody to tumor necrosis factor-alpha attenuate hemodynamic dysfunction and sepsis-induced acute lung injury.

A number of key mediators are implicated in the pathophysiology of sepsis. In previous studies of a septic porcine model, ibuprofen pretreatment prevented the early but not the late rise in pulmonary vascular resistance index (PVRI) and the early but not the late fall in arterial PO2 (PaO2), whereas monoclonal antibody to tumor necrosis factor alpha (anti-TNF alpha) prevented the late but not the early rise in PVRI and the late but not the early fall in PaO2. This study examined the impact of pretreatment with combined ibuprofen and anti-TNF-alpha on the course of sepsis and acute lung injury (ALI) in pigs. Three groups were studied for 5 hours. Groups I (n = 9) and II (n = 5) received a 1-hour infusion of Pseudomonas aeruginosa. Group II received ibuprofen (12.5 mg/kg) and anti-TNF-alpha (5 mg/kg) before P. aeruginosa, and a further bolus of ibuprofen at 120 minutes. Group III (n = 11) received sterile saline. Group I demonstrated a significant (p < 0.05) rise in plasma TNF-alpha that was abolished in group II. The SVRI in group II did not change significantly from baseline through the study and the SVRI rose sharply in group I following onset of the infusion of P. aeruginosa, as did PVRI. There was no significant change in PVRI from baseline in group II, except for the final 60 minutes; PVRI in group II was significantly less than in group I throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation.

Tumor necrosis factor (TNF alpha), both by direct action and by trafficking cells of the immune system, is implicated in cardiopulmonary derangements and PMN-mediated microvascular injury associated with gram-negative sepsis. We examined the effects of pretreatment with a monoclonal antibody to TNF alpha on PMN function, hemodynamic derangements, and alveolar capillary membrane damage in a septic porcine model. Anti-TNF alpha profoundly improved hemodynamic consequences in this model. Reduction in PMN CD11/18 receptor expression, lung myeloperoxidase activity, and attenuation of peripheral neutropenia (all P < 0.05) indicate that pretreatment significantly reduced lung sequestration of PMNs seen in septic controls. In contrast, PMN oxygen radical (O2-) generation was not significantly different from unprotected septic animals. Despite the presence of circulating PMNs primed for O2- burst, alveolar capillary membrane damage, assessed by bronchoalveolar lavage protein content and arterial PO2 was markedly attenuated in the treatment group (P < 0.05). We conclude that anti-TNF alpha suppresses systemic hemodynamic actions of TNF alpha. Further, it prevents upregulation of PMN adhesion receptors inhibiting PMN/endothelial cell interaction. This prevents formation of a "microenvironment," protected from circulating oxidant scavengers, into which sepsis-activated PMNs release their toxic products. Pretreatment with anti-TNF alpha monoclonal antibody thus affords global protection in porcine Gram-negative sepsis.

Animals↗
PubMed1992

Cerebellar ataxia in the elderly.

In a retrospective study of 624 elderly patients referred with falls and gait disorders, 45 patients were found to have ataxia. Cerebrovascular diseases were the most common underlying cause of ataxia (15 patients, 37%). Nine patients had hereditary/degenerative cerebellar ataxia. History suggesting alcohol as an underlying cause was established in two patients with cerebellar ataxia. Three patients had normal pressure hydrocephalus and their condition improved remarkably after surgery. No definite cause was found in five patients. Cranial computed tomography (CT) showed cerebral atrophy in 16 patients and in three patients there was evidence of atrophy of the cerebellar vermis. Four patients had femoral neck fractures and three patients had other fractures. In a 5-year follow-up five patients died with bronchopneumonia (11% mortality) and patients with dementia showed rapid deterioration. All patients were referred to the day hospital for rehabilitation. The best treatment outcome was achieved in patients who had a single cerebrovascular accident with no cognitive impairment and in those whose ataxia was secondary to medication. Fourteen patients (44%) moved to residential care while 27 (66%) continued to live in their homes with community support. We concluded that there is no evidence of increased mortality in the elderly patients with cerebellar ataxia. CT scan is mainly helpful in diagnosing specific diseases such as tumours or hydrocephalus. A significant proportion of elderly patients with ataxia may have reversible or treatable conditions and can pursue an independent life.

Aged↗
PubMed1983

Bacteraemia in a geriatric unit.

A retrospective study was made of 50 consecutive cases of bacteraemia treated in a geriatric unit. The mortality rate was 24%, the highest incidence occurring amongst the cases of hospital-acquired bacteraemia where only 1 of 7 cases survived the infection. Pyrexia, acute confusion, and falls were the commonest presenting symptoms. The most frequently identified tissue sources for the bacteraemia were the genito-urinary tract (24%) and the lungs (22%). In 20% of cases the source of infection was unidentified.

Aged↗
PubMed1975

The relationship between low leucocyte ascorbic-acid levels and tyrosine metabolism in the elderly.

Twenty-seven elderly men aged 69-94 years had tyrosine tolerance tests measured before and after receiving ascorbic acid 1 g daily for four days. There was a significant rise in the fasting and half-hourly mean plasma tyrosine levels after ascorbic acid administration in those subjects with an initial leucocyte ascorbic-acid level (LAA) below 15 micrograms/10(8) w.c.c. The peak of the tyrosine tolerance curve was also advanced following administration of ascorbic acid in those subjects with an initial LAA below 15 micrograms/10(8) w.c.c. A further ten elderly men aged 73-89 years had simultaneous measurements of the circadian rhythms of LAA, plasma cortisol and plasma tyrosine levels before and after receiving ascorbic acid 1 g daily for four days. All ten subjects showed a peak LAA level at 5 p.m. when saturated with vitamin C but there was no significant correlation between plasma cortisol changes and plasma tyrosine changes. Possible explanations for the results are discussed.

Aged↗