Frank Vinholt Schiødt

Serum Gc-globulin in the early course of multiple trauma

OBJECTIVES In patients with multiple trauma, actin released from damaged cells may cause severe circulatory disturbance due to thrombi formation. The aim of this study was to evaluate serum concentrations of the actin scavenger, Gc-globulin, in relation to the severity of injury and outcome. DESIGN Prospective, longitudinal, observational study. SETTING Trauma center at a university hospital. PATIENTS Twelve patients with multiple trauma, consecutively included, according to defined criteria. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Serum Gc-globulin concentrations were measured at the time of admission and daily thereafter for 1 wk or until death. In all patients, the Gc-globulin concentration was significantly low (p < .0001), and the proportion of Gc-globulin bound to actin was already increased compared with normal values (p < .0001) by the time of hospital arrival. There was an inverse correlation between the mean concentration of serum Gc-globulin in the first week after trauma and the Injury Severity Score (r = -0.72, p < .05). Surviving patients had a significantly (p < .05) higher concentration of serum Gc-globulin in the first week after trauma compared with nonsurvivors. CONCLUSIONS Serum concentrations of Gc-globulin were significantly low in trauma patients. The reduction took place within 60 mins after injury. Because the normal half-life of Gc-globulin is almost 48 hrs, our observations suggest a marked consumption of Gc-globulin immediately after the trauma. This finding could be the first clinical evidence that Gc-globulin plays a role in the systemic inflammatory response syndrome after trauma. This result is supported by the finding that lack of Gc-globulin was related to nonsurvival and the severity of the trauma.

Reduced serum Gc-globulin concentrations in patients with fulminant hepatic failure : Association with multiple organ failure

OBJECTIVE To evaluate the association between admission serum concentrations of the actin-scavenger, Gc-globulin, and the subsequent development of multiple organ failure in patients with fulminant hepatic failure. DESIGN Retrospective study. SETTING A hepatologic intensive care unit. PATIENTS Seventy-nine patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Serum admission concentrations of both total and nonactin-complexed (free) Gc-globulin were determined. The development of cardiovascular failure, renal failure, pulmonary failure, intracranial hypertension, and infections were recorded in each patient. Both total and free Gc-globulin values were significantly lower in the patients, compared with normal controls. The Gc-globulin values were significantly reduced in patients who subsequently developed cardiovascular failure (p < .01), intracranial hypertension (p < .001), and infections (p < .001), compared with those patients who did not. No differences were found between patients with and without pulmonary or renal failure. Patients with total Gc-globulin values in the lowest quintile had on average 2.6 organ failures, whereas patients with Gc-globulin concentrations in the highest quintile had 0.9 organ failures. The corresponding figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1 organ failures, respectively. Both total and free Gc-globulin were inversely correlated to the number of organ failures (p < .005 in both cases). Patients with multiple organ failure (> or = 2 organ failures) had significantly reduced Gc-globulin values compared with patients without multiple organ failure (p < .0001). CONCLUSIONS In patients with fulminant hepatic failure, the lowest admission Gc-globulin concentrations were associated with the subsequent development of cardiovascular failure, intracranial hypertension, and infections. Lack of Gc-globulin correlated significantly with the development of multiple organ failure and may be pathogenetically involved in this condition.

The value of plasma acetaminophen half-life in antidote-treated acetaminophen overdosage

A plasma acetaminophen (INN, paracetamol) half‐life of more than 4 hours has been correlated with hepatotoxicity in acetaminophen overdosing not treated with an antidote. Acetaminophen half‐life has not been studied in patients receiving the antidote N‐acetylcysteine.

Haemodynamic changes after high-volume plasmapheresis in patients with chronic and acute liver failure

Objective: To evaluate the haemodynamic changes during treatment with highvolume plasmapheresis in patients with chronic liver failure compared to patients with acute liver failure. Methods: Haemodynamic measurements were performed with a Swan‐Ganz catheter and thermodilution technique. High‐volume plasmapheresis (mean plasma exchange of 8.6 litres) was performed in 11 patients with chronic and 16 patients with acute liver failure. Results: In patients with chronic liver failure, systemic vascular resistance index was unaltered: 1193 ± 494 dynscm‐5m2 before treatment versus 1180±399 dynscm‐5m2 after. Mean arterial pressure increased from 69±11 mmHg to 78±13 mmHg (P<0.05) and cardiac output increased from 8.1 ±2.4l/min to 8.9±2.4 l/min (P<0.05) during highvolume plasmapheresis. In patients with acute liver failure, systemic vascular resistance index increased from 1154±628 dyns cm‐5m2 to 1614±738dynscm‐5m2 (P<0.001). In this group mean arterial pressure increased from 78±16mmHg to 95±10mmHg (P< 0.001) and cardiac output decreased from 9.6±3.7l/min to 8.2±2.9 l/min (P<0.01). Conclusion: The hyperkinetic circulation in chronic and acute patients was differently affected by high‐volume plasmapheresis. We suggest that in chronic liver failure both portosystemic shunting and chronic peripheral vasodilation may contribute to the hyperkinetic syndrome, whereas in acute liver failure a humoral factor which can be removed by high‐volume plasmapheresis is a main contributor.

Admission level of Gc-globulin predicts outcome after multiple trauma

BACKGROUND Actin is the dominating protein in mammalian cells. Release of excessive amounts of actin into the circulation may result in a condition resembling multiple organ failure. The purpose of this study was to determine if admission levels of Gc-globulin can predict survival after multiple trauma. Also, we wanted to compare the predictive ability of Gc-globulin with that of the TRISS-Like scoring system. METHODS Fifty-seven patients with a median ISS 18 (16-75) were included. All patients had a blood sample taken median 42 min after the injury (19-110 min). Serum Gc-globulin was measured by rocket immunoelectrophoresis. RESULTS On admission, all patients had significantly reduced levels of Gc-globulin compared with normal controls. Gc-globulin was significantly higher in the group of survivors (n = 41), compared with non-survivors (n = 16). Median 237 mg/l vs. 188 mg/l (P < 0.01). The predictive ability of Gc-globulin regarding death was similar to that of TRISS-Like with positive predictive values of 69%, a negative predictive value of 84%, a sensitivity of 56% and a specificity of 90%. CONCLUSIONS The predictive value of Gc-globulin regarding survival was similar to that of an established scoring system. Gc-globulin, alone or in combination with other parameters, may serve as a routine tool for early identification of patients at risk after severe injury, increasing the possibility of early intervention.

Primary (AL) amyloidosis with gastrointestinal involvement

Objective. Immunoglobulin light-chain (AL) amyloidosis is a rare disease that can affect several organs. The aim of this study was to characterize patients with gastrointestinal manifestations of AL amyloidosis, in terms of symptoms, biochemistry, and outcome. Material and methods. Retrospectively, patients with AL amyloidosis admitted for evaluation of malabsorption in a Department of Gastroenterology between January 2000 and December 2006 were identified. Results. A total of 11 patients (4 F, age 60 years, median (range) 50–69) were included in the study. Gastrointestinal amyloidosis was histologically verified in all patients. All patients had gastrointestinal symptoms, 8 of them prior to establishment of diagnosis. Median (range) delay from initial symptoms to diagnosis was 7 (0–24) months. The most prominent symptom was weight loss (n=10) averaging 7 (0–25) kg, followed by diarrhea (n=5). Steatorrhea (2 mild, 1 moderate, 1 severe) was found in 4 of 7 patients examined. At presentation, 9 patients had hypoalbuminemia and 6 patients had anemia. Three patients were treated with home parenteral nutrition. Five patients received conventional chemotherapy (oral melphalan and prednisone) and 5 patients underwent high-dose melphalan and autologous stem-cell transplantation. Five patients died within the observation period, at a median of 10 (3–36) months after the diagnosis was established. Non-survivors tended to have lower albumin levels on admission and more involvement of other organs compared to survivors. Conclusions. Most patients with gastrointestinal AL amyloidosis experience weight loss and all have signs of malabsorption. Despite treatment the prognosis is grave.

Prediction of hepatic encephalopathy in paracetamol overdose : A prospective and validated study

BACKGROUND Paracetamol overdose may cause hepatic encephalopathy (HE). This condition demands specialized care and, in some instances, liver transplantation evaluation. No model is available for predicting HE. We aimed to set up and validate a model for predicting the occurrence of HE in paracetamol overdose. METHODS Prospectively, 161 patients with single-dose paracetamol overdose and no HE (defined as hepatic coma grade II or more) on admission were studied during a 26-month period. Patients admitted during the first 13-month period constituted a learning set to construct a model to predict the occurrence of HE. Patients admitted in the second 13-month period constituted the validation set. Serial biochemical variables (measured twice daily), the time line after the overdose, and demographic data were used for univariate testing, and significant factors were assessed in various multiple logistic regression analyses. RESULTS Thirty-two patients (20%), 15 in the first period and 17 in the second, developed HE grade II. The best model (the highest chi-square) for HE included: log10 (hours from overdose to antidote treatment), log10 (plasma coagulation factors on admission), and platelet count hours from overdose (chi-square = 41.2, P < 0.00001). In the validation set 88% (confidence interval (CI), 64%-99%) of the patients who developed HE were correctly predicted by the constructed model, whereas 90% (CI, 79%-96%) of the patients in the non-HE group were correctly predicted. CONCLUSIONS The constructed model for predicting HE in paracetamol overdose proved sensitive and accurate in the validation set and should be valuable for transferring high-risk patients to a liver intensive care unit/transplantation facility.

Circulating mannan-binding lectin, M-, L-, H-ficolin and collectin-liver-1 levels in patients with acute liver failure.

The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan‐binding lectin (MBL), M‐, L‐, and H‐ficolin and collectin‐liver‐1 (CL‐L1), which are predominantly synthesized in the liver. We aimed to study lectin levels in ALF patients and associations with clinical outcome.