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Biomedical subjects

M C Bellamy

Publications and source records attributed to M C Bellamy.

At least 19 recordsLinked to original sources

Effect of perioperative steroids on renal function after liver transplantation.

Subclinical renal dysfunction is thought to occur as a systemic manifestation of ischaemia-reperfusion injury of other organs. Liver transplantation is associated with major ischaemia-reperfusion injury. Thirty-four patients undergoing elective liver transplantation were randomly allocated to receive either saline or 10 mg.kg(-1) methylprednisolone on induction of anaesthesia. Urine was taken for N-acetyl-beta-D-glucosaminidase, creatinine and other markers of tubular function. Serum chemistry was measured for 7 days. Creatinine concentration increased in the saline group but not in the methylprednisolone group (p < 0.0001), with the greatest difference on the third postoperative day (mean (SD) 164.8 (135.8) mumol.l(-1)vs 88.5 (39.4) mumol.l(-1), respectively). Similar changes were seen in postoperative alanine transferase (865 (739) U.l(-1)vs 517 (608) U.l(-1), respectively; p < 0.0001) on the second postoperative day. Both groups exhibited increases in markers of renal tubular dysfunction and of glomerular permeability. Patients in the saline group sustained more adverse events (8/17 (47%) vs 2/17 (12%); p = 0.02). The data confirm increased proximal tubular lysosomal turnover, consistent with an increased tubular protein load, following liver transplantation, and suggest that methylprednisolone protects against renal and hepatic dysfunction.

Acetylglucosaminidase↗

Tetanus in a subcutaneous drug abuser: ineffectiveness of intrathecal baclofen.

This report discusses the issues involved in the diagnosis and management of tetanus. A 29-year-old female with a history of illicit drug use presented with progressive tetany secondary to an abscess on her forearm from subcutaneous injections. She was managed in the intensive care unit for 29 days and was discharged to the ward. The main issue in her management was control of tetanic episodes interfering with ventilation and resistant to intrathecal baclofen. Other therapeutic strategies aimed at reducing spasms included magnesium, atracurium, pancuronium, midazolam, propofol and dantrolene. We conducted searches on Medline, PUBMED and the Cochrane Database of Systematic Reviews using the following terms: tetanus, treatment, therapy, drug abuse, magnesium, baclofen and human anti-tetanus immunoglobulin (hAIG). The current strategies involved in treating tetanus are discussed.

Adult↗

Interleukin 13 and inflammatory markers in human sepsis.

BACKGROUND: Interleukin (IL) 13 is an anti-inflammatory cytokine that reduces inflammatory cytokine production, and enhances monocyte survival and MHC class II and CD23 expression. The only report of IL-13 in human sepsis noted no increase in IL-13 concentration, in contrast to animal data. This study further examined the expression of IL-13 in relation to human sepsis. METHODS: In a prospective observational study of 31 patients (24 men) with sepsis or septic shock, high-sensitivity enzyme-linked immunoabsorbent assay (ELISA) was used to quantify levels of tumour necrosis factor (TNF) alpha on admission, and on days 1, 3, 5 and 7 thereafter. IL-13 and IL-2 were assayed by standard ELISA, and HLA-DR on CD14-positive monocytes was measured by flow cytometry. RESULTS: Twenty-three patients developed septic shock. Monocyte HLA-DR levels showed greater depression and a slower recovery in shocked than non-shocked patients. The serum IL-13 concentration was significantly higher in the shocked group from admission to day 3, but subsequently decreased to levels similar to those in the non-shocked group. IL-13 concentrations were higher in non-survivors. The TNF-alpha concentration was higher in those with septic shock than in those without. The TNF-alpha level correlated with IL-13 concentration (r(S) = 0.61, P = 0.002). The IL-13/TNF-alpha ratio was greater in patients with shock than those with sepsis only (P = 0.017). IL-2 was undetectable. CONCLUSION: In human sepsis and septic shock, IL-13 correlated with TNF-alpha expression, but its effect on HLA-DR class II molecules remains unclear.

Adult↗

Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding.

UNLABELLED: The management of bleeding gastric varices has not been standardized. Although transjugular intrahepatic portosystemic shunt (TIPS) is used in most centers, endoscopic treatment with N-butyl-2-cyanoacrylate (cyanoacrylate) glue has recently been shown to be effective. Cost-effectiveness analyses of these methods are lacking. METHODS: We performed a retrospective review of patients with bleeding gastric varices treated either by TIPS or cyanoacrylate glue injection. Economic analysis was based on direct costs for a fixed financial year. The two groups were compared for a period of 6 months follow-up, to liver transplantation, or death for each patient. RESULTS: Between January, 1995 and December, 1999, 20 patients with bleeding gastric varices had TIPS; 23 patients had cyanoacrylate glue injection from January, 2000 to October, 2001. There were no significant differences between the two groups in patient characteristics, transfusion requirement, and gastric variceal anatomy. In the TIPS group, 15/20 patients had the procedure performed within 24 h of hemorrhage, and 90% of stent insertions were successful. Complications consisted of two cases of pulmonary edema, two cases of severe encephalopathy, and a 15% stenosis rate at 6 months. In the glue group, there were 3 +/- 1.5 endoscopies and 2 +/- 1 injections per patient, with a 96% initial hemostasis. There was one case of (glue) pulmonary embolism and one blocked front endoscope lens, which required repair. The initial rebleed rate was significantly lower in patients who had TIPS (15% vs 30%, p = 0.005). The inpatient stay was shorter in the glue group (13 +/- 1 vs 18 +/- 2 days, p = 0.05), but there was no difference in the overall mortality rate. The median cost within 6 months of initial gastric variceal bleeding was $4,138 US dollars ($3,009-$8,290 US dollars) for glue versus $11,906 US dollars ($8,200-$16,770 US dollars) for TIPS (p < 0.0001). CONCLUSION: In this comparable group of patients, cyanoacrylate glue injection was more cost effective than TIPS in the management of acute gastric variceal bleeding. A prospective, randomized trial would be required to confirm our analysis.

Acute Disease↗

Injury patterns associated with mortality following motorcycle crashes.

All patients involved in motorcycle crashes admitted to various hospitals in the Yorkshire region of UK between January 1993 and December 1999 were retrospectively reviewed to identify the factors that are likely to predict a reduced survival. Of the 1239 patients requiring hospital admission, 74 died. The probability of reduced survival was estimated by a logistic regression model using independent variables such as head injury, thoracic trauma, abdominal injury, spinal injury and pelvic fracture and a compound variable of pelvic fracture combined with a long bone fracture. The odds ratio for head injury was 0.349, chest injury 0.39, abdominal injury 0.42, and the compound variable (pelvis plus a long bone fracture) 0.576. The mean injury severity score (ISS) in the fatal group was 35.96 compared to 12.2 in the group that survived (P<0.01). There was a significant difference in the Glasgow coma scale (GCS) between patients wearing a helmet and those that did not wear any protective headgear (P=0.0007). Head injury followed by chest and abdominal trauma were found to predict a reduced survival rate. Use of helmets should continue to be compulsory. Chest and abdominal injuries should be diagnosed and treated early to reduce mortality.

Abdominal Injuries↗

Motorcycle injury and survival: improving outcomes.

The aim of this study was to examine all motorcycle accident injuries presenting in Yorkshire, United Kingdom, and to assess the impact of the introduction of a consultant-led trauma team on mortality, 1993-2000. Data were collected on 1239 patients. Factors independently associated with survival by logistic regression were: the presence of abdominal trauma (odds ratio 0.46, 95% confidence interval 0.31 to 0.68), the presence of chest trauma (OR 0.41, 0.29 to 0.6), the presence of head trauma (OR 0.36, 0.30 to 0.45), requirement of a blood transfusion in the emergency room (OR 0.88/unit of blood, 0.72 to 1.07), presence of the trauma team (OR 0.43, 0.16 to 1.03) and the number of years into the program (OR 1.34/year, 1.07 to 1.67). The single factor determining improved survival was the time into the study. This shows that treatment of motorcycle trauma has improved overall with time. We propose that the introduction of uniform treatment protocols and improvements in the general standard of care have had a great effect.

Accidents, Traffic↗

Functional iron deficiency, infection and systemic inflammatory response syndrome in critical illness.

To investigate the prevalence and clinical relevance of functional iron deficiency in the critically ill, we performed a prospective observational study in a university hospital general intensive care unit. We collected patient demographics, severity of illness data, haematological and biochemical variables in 51 consecutive admissions. We recorded episodes of culture-positive infection. Functional iron deficiency (FID), measured by red cell hypochromasia on flow cytometry, was present in 35% of patients at admission to intensive care. FID patients were of similar age, diagnosis, APACHE score, sequential organ failure assessment (SOFA) score, haemoglobin, serum B12, folate and ferritin to patients without FID. However, patients with FID had a prolonged intensive care stay compared with non-FID patients (P<0.001) and increased time to hospital discharge (P=0.09). Duration of intensive care stay correlated with severity of FID (r=0.33, P<0.02). Systemic inflammatory response syndrome (SIRS) was present for longer in those with FID (P<0.02). Overall mortality did not differ between groups. No difference was seen in the incidence of positive cultures between those with FID (9/18 patients) and those without FID (15/33 patients). FID was independently associated only with abnormal white blood cell count (WBC < 4 or > 11 x 10(9) x l(-1)) at admission to ICU, P=0.007, but not with positive cultures. There is a high prevalence of FID in intensive care, associated with an increased duration of stay and duration of SIRS. We have been unable to demonstrate a link with infection, either as a predisposing factor or as an acute response.

APACHE↗

Immediate IL-10 expression following major orthopaedic trauma: relationship to anti-inflammatory response and subsequent development of sepsis.

OBJECTIVE: To assess the relationship between IL-10 release and anti-inflammatory response following blunt trauma. DESIGN: Prospective longitudinal clinical study. SETTING: Departments of trauma and anaesthetics in a university teaching hospital. PATIENTS: Forty-eight adult patients with a mean injury severity score of 14.5 (range 9-57) were prospectively studied following blunt trauma. MEASUREMENTS AND RESULTS: Venous blood samples were collected on arrival and at 16 and 24 h, and at 3, 5, and 7 days. Peripheral blood mononuclear cell (HLA-DR) expression on CD14 + monocytes was quantified by flow cytometry and serum IL-10 was assayed by ELISA. Anti-inflammatory response was defined as monocyte HLA-DR expression of less than 30% of that seen in healthy controls. Serum IL-10 levels in trauma patients on arrival was significantly elevated, 70.0 [48.0-92.1, 95% confidence interval, (CI)] compared to the control group, 3 (0-5) (P < 0.0001), and monocyte HLA-DR expression was significantly lower, 14.2 (12.1-16.3, 95% CI), in patients versus 25.2 (22.4-28.1) in controls (P < 0.001). Patients with low HLA-DR expression (n = 14) had significantly higher serum IL-10 levels than those whose HLA-DR expression remained above 30% of the control value (n = 34), (P < 0.038). In patients who developed sepsis (n = 11), serum IL-10 levels were greater on admission, [143.7 (80.2-207.2) pg/ml(-1)], and remained elevated during the study period compared with non-complicated patients, [50.16 (33.5-66.8) pg/ml(-1)]. Immediate IL-10 (2 h following trauma) was negatively correlated with simultaneous HLA-DR expression, (r = -0.49, P = 0.0005). CONCLUSION: These findings support the view that IL-10 release regulates monocyte HLA-DR expression and may be related to an anti-inflammatory response and development of sepsis following trauma.

Adult↗

Pulmonary artery catheterization and mortality in critically ill patients.

Pulmonary artery catheters are widely used in intensive care, but evidence to support their widespread use in sparse. Some published data suggest that greater mortality is associated with use of these catheters. The largest study to date looked at > 5500 patients in several centres in America and found a greater 30 day mortality in those patients receiving a pulmonary artery catheter. We tested the hypothesis that, on our intensive care unit, mortality was greater for those patients receiving a pulmonary artery catheter. Using a propensity score to account for severity of illness, the odds ratio for mortality in those patients receiving a pulmonary artery catheter was 1.08 (95% confidence interval 0.87-1.33). We believe that continued use of the pulmonary artery catheter is safe; a large randomized controlled trial examining outcome is unlikely to provide an adequate answer.

APACHE↗

Ex vivo and in situ resection of inferior vena cava with hepatectomy for colorectal metastases.

OBJECTIVE: To describe the surgical techniques and early results of inferior vena cava (IVC) resection in patients with advanced liver tumors. SUMMARY BACKGROUND DATA: Involvement of the IVC by hepatic tumors, although rare, is considered inoperable by standard resection techniques. Concomitant hepatic and IVC resection is required to achieve adequate tumor clearance. METHODS: Between February 1995 and February 1999, 158 patients underwent hepatic resection for colorectal metastases in the authors' unit. Eight patients, aged 42 to 80 years (mean 62 years), with hepatic metastases from colorectal cancer underwent concomitant resection of the IVC and four to six hepatic segments. Resections were carried out under total hepatic vascular exclusion in four patients and ex vivo in four patients. Between 30 degrees and 360 degrees of the retrohepatic IVC was resected and replaced with an autogenous vein patch (n = 1), a ringed Gore-Tex tube graft (n = 2), a Dacron tube graft (n = 1), or a patch (n = 3) or was repaired by primary suturing (n = 1). RESULTS: There were two early deaths from multiple organ failure. One patient survived 30 months after ex vivo resection but died of renal cell carcinoma, and another died with recurrent disease at 9 months. The remaining four patients remained alive 5 to 12 months after surgery, with no hepatic failure or venous obstruction; tumor recurrence was present in two. Nonthrombotic occlusion of the neocava occurred in one patient and was stented successfully. CONCLUSIONS: Although concomitant hepatic and IVC resection is associated with a considerable surgical risk, this aggressive surgical approach offers hope for patients with hepatic tumors involving the IVC, who would otherwise have a dismal prognosis. This procedure can be performed under total hepatic vascular exclusion, with or without venovenous bypass, and by ex vivo bench resection.

Adenocarcinoma↗

Interleukin-10 release and monocyte human leukocyte antigen-DR expression during femoral nailing.

This study determined the effect of femoral nailing on the expression of monocyte Class II antigens and interleukin-10 release and sought to differentiate any differences in the release of these elements of immune reactivity in patients undergoing reamed and unreamed nailing. Thirty-two patients presenting with an acute femoral fracture were studied. In 15 patients, the femoral fracture was stabilized with a reamed technique and in 17 patients with an unreamed technique. Venous blood samples were taken at presentation, at anesthetic induction, immediately after nail insertion, and subsequently at 1, 4, and 24 hours and at 3, 5, and 7 days after surgery. Serum interleukin-10 was measured by an enzyme-linked immunosorbent assay, and monocyte human leukocyte antigen-DR expression was quantified by flow cytometry. Serum interleukin-10 release and human leukocyte antigen-DR expression on monocytes showed a clear response to the nailing procedure. The group of patients undergoing a reamed femoral nailing procedure showed significantly higher interleukin-10 release and a significant depression in the expression of human leukocyte antigen-DR on monocytes compared with those whose nail had been inserted unreamed. One patient in the reamed femoral nailing group died of adult respiratory distress syndrome 3 days after injury. Reamed intramedullary nailing appears to be associated with greater impairment of immune reactivity than is the unreamed nailing technique.

Adolescent↗

Laser Doppler flowmetry is useful in the clinical management of small bowel transplantation. The Liver Transplant Group.

OBJECTIVE: Laser Doppler flowmetry (LDF) has been used as a research tool to measure splanchnic perfusion. In this report, we aim to demonstrate the clinical value of this technique in perioperative monitoring of transplanted small bowel. METHODS: A 24 year old man underwent small bowel transplantation using a previously described technique. Microvascular blood flow in the transplanted bowel was measured using an LDF splanchnic probe. Postoperatively this was applied to the stoma facilitating direct measurements of graft mucosal flow. Measurements (perfusion units (PU)) were documented prior to implantation, post-reperfusion, postoperatively, during graft ischaemia, and in response to therapeutic interventions (dopexamine and phenylephrine infusions). RESULTS: Prior to transplantation, biological zero was established. Flow at five, 15, and 60 minutes after reperfusion was 74 (1.9) PU, 87.5 (3.3) PU, and 141.5 (2.5) PU, respectively. Postoperative mucosal flow was 141.6 (2.9) PU. Subsequent LDF measurement detected absence of flow even though clinical signs suggested only moderate reduction. This was confirmed on surgical re-exploration and facilitated prompt resection of a non-viable segment. Fluid and dopexamine administration resulted in a dose dependent improvement in flow, independent of blood pressure. Addition of phenylephrine increased total mucosal flow and unmasked a cyclical component. CONCLUSION: This case demonstrates the clinical value of LDF as an "alarm" to indicate graft perfusion failure and as a monitor for therapeutic interventions. Phenylephrine and dopexamine may both be of value in improving mucosal flow in the transplanted small bowel.

Adrenergic alpha-Agonists↗

Monocyte human leukocyte antigen-DR expression correlates with intrapulmonary shunting after major trauma.

BACKGROUND: Severe injury is often complicated by the development of sepsis and the adult respiratory distress syndrome. Since the outcome from severe injury also correlates with changes in monocyte human leukocyte antigen (HLA)-DR expression in such patients, the present study aimed to determine whether or not there was a relationship between monocyte HLA-DR expression and indicators of early pulmonary dysfunction. METHODS: Monocyte HLA-DR expression and serum interleukin (IL)-6 were measured on admission and then again on days 1, 3, 5, and 7 after major injury in 29 patients admitted for the management of trauma with an injury severity score of 9 or more. Noninvasive intrapulmonary shunt measurement was also performed in all these patients within 6 hours of emergency surgery in all patients. RESULTS: Monocyte HLA-DR followed the characteristic suppression followed by recovery in those who followed an uncomplicated course but progressively declined in those who suffered septic complications. The degree of intrapulmonary shunting observed 6 hours after injury in the patients who developed sepsis was significantly higher than that in the uncomplicated group. Peak monocyte HLA-DR expression during the recovery phase correlated inversely with the degree of intrapulmonary shunting. CONCLUSIONS: The degree of intrapulmonary shunting observed following severe trauma correlates with the failure of circulating monocytes to re-express HLA-DR antigen, and this may provide some insights into the early events that result in the adult respiratory distress syndrome after major injury.

Adult↗

Extravascular lung water and acute respiratory distress syndrome--oxygenation and outcome.

We studied eleven consecutive patients to assess the influence of extravascular lung water on clinical outcome. All patients were mechanically ventilated using a standardized protocol. Inspired oxygen concentration was adjusted to an initial target PaO2 of greater than 8.0 kPa (60.8 mmHg). All patients received inhaled nitric oxide (NO) at a concentration of 20 ppm. Extravascular lung water index (EVLWI) was measured by a dual indicator technique (COLD Z-021 monitoring system, Pulsion, Munich, Germany). Patients were managed with fluids and inotropes according to a standard protocol. Median age was 45 (range 27-60) years, mean APACHE II score on admission 31 (range 17-36), duration of mechanical ventilation 15 (range 6-28) days, mean admission Murray lung injury score 2.5 (range 2-3) and admission EVLWI 20.8 (range 8.7 to 54.7) ml.kg-1. The only variables independently predictive of PaO2/FiO2 ratio were serum albumin (B = 1.7 +/- 1.61) and EVLWI (B = -2.1 +/- 0.47), r2 = 0.33, P < 0.0001. In severe ARDS, (PaO2/FiO2 < 150 mmHg), mean EVLWI was 24.4 (22.4 to 26.4, 95% confidence intervals) ml.kg-1 compared with 15.1 (12.2 to 18.0) ml.kg-1 during moderate ARDS (P < 0.001). Serum albumin likewise differed, 29.4 (27.6 to 31.2) vs 35.1 (31.8 to 38.4) g.l-1, P < 0.005. PAOP was higher during periods of poor oxygenation, 12.7 (11.9 to 13.5) vs 9.3 (7.9 to 10.7) mmHg, P < 0.001. The four survivors had greater initial EVLWI than non-survivors, 31 (24.1 to 37.9) vs 20.7 (16.0 to 25.4) ml.kg-1, P = 0.034 and showed a greater reduction in lung water, 15.2 (9.3 to 21.1) vs 5.4 (2.1 to 8.7) ml.kg-1, P = 0.013.

APACHE↗

Stimulation of the inflammatory system by reamed and unreamed nailing of femoral fractures. An analysis of the second hit.

It has been suggested that reamed intramedullary nailing of the femur should be avoided in some patients with multiple injuries. We have studied prospectively the effect of femoral reaming on the inflammatory process as implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). We studied changes in the levels of serum interleukin-6 (IL-6) (proinflammatory cytokine), neutrophil CD11b (C3) receptor expression (activated neutrophil adhesion molecule), serum soluble intracellular adhesion molecule (s-ICAM-1), serum soluble E-selectin (the soluble products of endothelial adhesion molecules) and plasma elastase (neutrophil protease) in a series of patients with femoral fractures treated by nailing. We have also compared reamed nailing with unreamed nailing. We found that the levels of serum IL-6 and elastase rose significantly during the nailing procedure indicating a measurable 'second hit'. There was no clear response in leukocyte activation and no difference in the release of endothelial adhesion molecule markers. There was no significant difference between groups treated by reamed and unreamed nailing. Although clinically unremarkable, the one patient who died from ARDS was shown to be hyperstimulated after injury and again after nailing, suggesting the importance of an excessive inflammatory reaction in the pathogenesis of these serious problems. Our findings have shown that there is a second hit associated with femoral nailing and suggest that the degree of the inflammatory reaction may be important in the pathogenesis of ARDS and MOF.

Adolescent↗