Serum interleukin-6 in relation to acute-phase reactants and survival in patients with renal cell carcinoma

Patients with malignancies often present with signs of inflammatory reactions such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Since interleukin-6 (IL-6) is a possible regulator of these reactions and has been proposed as a predictor of prognosis, the aim of the study was to analyse its clinical significance in patients with renal cell carcinoma. Serum samples were collected from 196 patients before any treatment. IL-6 was analysed by an enzyme-linked immunoassay and compared with tumour grade, stage, acute-phase reactants and survival. Patients with renal cell carcinoma had significantly higher IL-6 levels (mean 28.1 +/- 63.4 ng/l; median 8.3 ng/l) compared with controls (mean 1.7 +/- 2.6 ng/l; median 0.5 ng/l; P < 0.001). Serum IL-6 levels in patients with distant metastases were significantly higher than for patients with tumours confined to the kidney (P = 0.02). This difference was more pronounced when serum IL-6 levels in patients with poorly differentiated tumours were compared with well-differentiated tumours (P < 0.001). A significant correlation between the acute-phase reactants CRP, ESR and IL-6 levels was found. Survival time was significantly shorter (P = 0.001) for patients with IL-6 levels above the median serum level compared with patients with lower levels. Similar significant prognostic results were obtained in the group of patients with metastatic disease, but not in group of patients with stage I-III. Serum levels of IL-6 correlated to tumour stage, grade and acute-phase reactants. Increased levels were related to the presence of metastases and adverse survival. Serum IL-6 proved univariate prognostic information but this prognostic significance was lost using a multivariate analysis.     

Identification of glutathione S-transferase isozymes and gamma-glutamylcysteine synthetase as negative acute-phase proteins in rat liver

Because acute infection and inflammation affect drug metabolism and drug-metabolizing enzymes, the effect of the acute-phase response on the expression of glutathione S-transferase (GST) isoenzymes, glutathione synthesis, and several antioxidant enzymes was investigated. Hepatic expression of GST isozymes, positive and negative acute-phase reactants, and antioxidant enzymes were determined by Northern blotting and hybridization with gene-specific oligonucleotide probes after lipopolysaccharide treatment of rats. Lipopolysaccharide caused the expected acute-phase response as judged by the increased expression of positive and decreased expression of negative acute-phase proteins. The messenger RNA (mRNA) expression of the major hepatic rat GST isozymes A1, A2, A3, M1, and M2 was decreased 50% to 90%. Total hepatic GST activity toward 1-chloro-2,4-dinitrobenzene was also significantly decreased. mRNA expression of gamma-glutamylcysteine synthetase (GCS) large subunit and catalase was reduced by approximately 60%. GCS enzyme activity was also decreased, resulting in a 35% decrease in the hepatic content of reduced glutathione 4 days after lipopolysaccharide challenge. Mn-Superoxide dismutase expression was increased 13-fold, and thioredoxin level was elevated 3-fold after lipopolysaccharide challenge. The expression of all parameters determined returned to near control levels 7 days after treatment. Together, these data show that GSTs and GCS are negative acute-phase proteins and that decreased GCS activity results in a decrease in hepatic glutathione content. Thus, in addition to the phase I drug-metabolizing enzymes known to be decreased during the acute-phase response, some phase II enzymes involved in the elimination of xenobiotics and carcinogens are also decreased.     

Effect of flunixin meglumine on plasma prostanoid concentrations in horses with colic in the perioperative period

In the present study the significance of eicosanoids in the development of shock in horses on the basis of ileus has been investigated using the prostanoids thromboxane B2 (TXB2) and prostaglandine E2 (PGE2) as indicators. The prostanoid synthesis inhibitor flunixin meglumine was to be examined regarding its efficacy in the effective blockade of the synthesis of these mediators within the peri-operative timeframe as well as its effects on clinical signs and laboratory parameters. 21 horses suffering from ileus and ready for surgical intervention received an intravenous flunixin dosis of 1.1 mg/kg body weight immediately after the initial examination and prior to the surgical procedure. 20 colic horses receiving surgical treatment without application of the drug served as control group. Reference data concerning the approximate standard plasma levels of the prostanoids were determined in 10 healthy horses. Plasma levels of thromboxane B2 and prostaglandine E2 in all colic horses, treatment group as well as controls, initially proved to be significantly higher than the reference values in healthy horses. The untreated control group showed plasma levels highly exceeding the standards within the course of investigation. The application of flunixin meglumine resulted in an effective inhibition of the prostanoid synthesis. Post-operatively as well as within the whole period of investigation the plasma levels of PGE2 and TXB2 of the treated group were considerably lower than those of the control group. Flunixin meglumine had a favorable effect on several cardiovascular parameters. The experimental data concerning the effects of flunixin meglumine thus could be validated in a clinical setting, especially the effective inhibition of the cyclooxygenase enzyme system. The application of the prostanoid synthesis inhibitor flunixin meglumine can be judged as being effective in limiting shock progress in the peri-operative setting given reliable diagnosis.     

Induction of the acute-phase reaction increases heparin-binding proteins in plasma

We have previously demonstrated that the nonspecific binding of unfractionated heparin (UFH) to plasma proteins has a marked modulating effect on its anticoagulant activity. Since some heparin-binding proteins are also acute-phase-reactant proteins, we explored the possibility that the induction of the acute-phase response can increase the plasma concentrations of heparin-binding proteins. The recovery of a fixed amount of UFH or low-molecular-weight heparin (LMWH) added in vitro to rat plasma samples obtained at various time intervals after the administration of intravenous endotoxin or subcutaneous turpentine was compared with that of saline-treated control animals. The anti-factor Xa activity was measured in the plasma samples before and after the addition of a chemically modified low-affinity heparin (LAH) to displace the proportion of the added heparin that is reversibly bound to plasma proteins. Our results show that at 6 hours post-endotoxin and at 24 hours post-turpentine treatment, virtually no anti-factor Xa activity could be measured in the plasma samples, while the expected levels were obtained for control plasma. After the addition of LAH to displace protein-bound UFH, essentially the same anti-factor Xa levels were measured in the plasma from all three treatment groups. These results indicate that induction of the acute-phase reaction can dramatically increase the levels of heparin-binding proteins in rat plasma. In addition, we compared the anti-factor Xa recovery of UFH with that of an LMWH from the plasma of endotoxin- and saline-treated rats and demonstrated that LMWH binds less to plasma proteins than UFH, even in plasma in which the levels of heparin-binding proteins are markedly elevated. The recovery of a fixed amount of UFH added in vitro to human plasma from septic patients was also reduced, but not to the same extent as seen in rat plasma. Removal of candidate heparin-binding and acute-phase proteins by immunodepletion indicated that vitronectin plays an important role in the nonspecific binding of UFH in patient plasma.     

Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 +/- 3 years (mean +/- SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1 beta and IL-6 were found to be 15-fold higher on admission (122 +/- 9 pg mL-1 and 60 +/- 4 pg mL-1 respectively), whereas TNF-alpha was three-fold higher (102 +/- 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 +/- 1 mg L-1), whereas fibronectin levels were reduced (242 +/- 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-alpha serum level (127 +/- 7 vs. 86 +/- 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-alpha (-7.2 +/- 0.7 vs. -3.8 +/- 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 +/- 3.0 vs. -54.6 +/- 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 +/- 1.0 vs. 11.7 +/- 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.     

Abnormalities in oxygenation, coagulation, and fibrinolysis in colonic blood of horses with experimentally induced strangulation obstruction

OBJECTIVE: To measure arterial and venous blood gas, coagulation, and fibrinolysis variables in blood from isolated segments of control and ischemic large colons for the purpose of identifying variables for rapid, indirect assessment of colonic mucosal injury. DESIGN: Variables were determined at specific intervals during the 4-hour study (3 hours of ischemia and 1 hour of reperfusion). ANIMALS: Seven clinically normal horses between 2 and 15 years old. PROCEDURES: Horses underwent laparotomy and occlusion of the lumen and vasculature of the mid-portion of the pelvic flexure of the large colon. During ischemia of 1 randomly-chosen colonic segment, variables were measured to determine colonic mucosal damage and were compared with histologic scores of colonic biopsy specimens. RESULTS: Significant (P < 0.05) differences from control values were observed over time for venous pH, PCO2, PO2, oxygen saturation, oxygen content, arteriovenous oxygen difference, and lactate and glucose concentrations. Mean histologic scores of biopsy specimens obtained from ischemic colons were significantly (P < 0.05) greater (indicating greater damage) than those from control colons, and increased significantly (P < 0.05) with duration of ischemia. CONCLUSIONS: Venous lactate, oxygen saturation, and PO2 values were the most significant predictors of the severity of histologic damage within the ischemic colons (R2 = 0.661). CLINICAL RELEVANCE: Venous blood gas and lactate values in the large colon are good predictors of the amount of intestinal damage incurred during 3 hours of ischemia, and may be clinically useful for the rapid determination of colonic viability.     

Interaction of heparin with canine coagulation proteins: in vivo and in vitro studies

The effects of heparin on the coagulation profile and on specific factor activity in canine plasma have been examined both in vivo and in vitro. The results show that the prolongation of the partial thromboplastin time of plasma produced by heparin is, at least in part, the result of the interaction of heparin with the intrinsic Factors VIII, IX and XI and the inhibition of their procoagulant activity by heparin. A significant correlation was found between the partial thromboplastin time assay and the circulating heparin activity following intravenous administration of heparin to dogs. The results confirm the suitability of the partial thromboplastin time assay for monitoring heparin therapy in the dog.     

Ovarian torsion as a cause of colic in a neonatal foal

A 1-week-old Morgan filly was evaluated because of acute signs of abdominal pain of 7 hours' duration. On admission, physical examination findings were unremarkable; however, radiography of the abdomen revealed slight distention of the small intestine. Signs of abdominal discomfort were detected during several hours of observation. Abnormalities were not evident during gastroscopic evaluation. Therefore, exploratory laparotomy was performed. The only abnormal finding was infarction of the left ovary secondary to a 720 degrees torsion of the mesovarium. The vascular pedicle was ligated and the ovary was removed. Recovery from anesthesia and surgery was satisfactory, and the foal was discharged from the hospital 5 days after surgery. Two years later, it appeared to be clinically normal. Review of the recent veterinary literature failed to find reports of ovarian torsion as a cause of signs of abdominal pain in horses. Ovarian torsion should be considered as a differential diagnosis in fillies with acute signs of abdominal pain, especially when laparotomy fails to reveal abnormalities associated with the gastrointestinal tract.     

Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.     

Identification of acute-phase proteins (APP) in circulating immune complexes (CIC) in esophageal cancer patients'' sera

OBJECTIVES: We describe the attitude and views of general practitioners towards the menopause and hormone replacement therapy (HRT) in metropolitan Brisbane, Australia. METHODS: A total of 216 general practitioners were nominated by a random sample of urband-welling women aged 45-54 years who formed the Brisbane Women's health study. A 20-30 minute face-to-face questionnaire with the general practitioners was administered and analysed by demographic characteristics. RESULTS: There was a 93% response rate. Management of the menopause and HRT was routinely undertaken by general practitioners for their own patients. After deciding to initiate HRT, > 60% of general practitioners ordered five investigations or more. They may have confused the risk of thrombo-embolism from oestrogens used in the post-menopause with that for contraception. There were differences between male and female practitioners in some areas. Male general practitioners, in particular, reported more difficulty with tailoring and adjusting regimes. CONCLUSIONS: Specific areas for further education are explored to meet the educational needs of general practitioners.     

Pharmacokinetics of heparin and its pharmacodynamic effect on plasma lipoprotein lipase activity and coagulation in healthy horses

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity. Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 mumol of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.     

Ultrasonography by emergency physicians in patients with suspected ureteral colic

We performed a prospective study of patients with suspected ureteral colic to evaluate the test characteristics of bedside renal ultrasonography (US) performed by emergency physicians (EPs) for detecting hydronephrosis, and to evaluate how US can be used to predict the likelihood of nephrolithiasis. Thirteen EPs performed US, recorded the presence of hydronephrosis, and made an assessment of the likelihood of nephrolithiasis. All patients underwent i.v. pyelography (IVP) or unenhanced helical computed tomography (CT). There were 126 patients in the study: 84 underwent IVP; 42 underwent helical CT. Test characteristics of bedside US for detecting hydronephrosis were: sensitivity 72%, specificity 73%, positive predictive value (PPV) 85%, negative predictive value (NPV) 54%, accuracy 72%. The PPV and NPV for the ability of the EP to predict nephrolithiasis after performing US were 86% and 75%, respectively. We conclude that bedside US performed by EPs may be used to detect hydronephrosis and help predict the presence of nephrolithiasis.     

Lipid metabolism in horses with hyperadrenocorticism

Lipid metabolism was studied in 21 horses with hyperadrenocorticism. To be included in the study, horses had to have histologic evidence of a pars intermedia adenoma found at necropsy (n = 9), a baseline ACTH concentration greater than 400 pg/ml (n = 6), or a plasma cortisol concentration 2 hours after i.v. administration of 25 IU of ACTH greater than 413 nmol/L (n = 16). Mean +/- SD baseline plasma cortisol concentration was 338 +/- 261 nmol/L (n = 20), mean +/- SD plasma insulin concentration was 97 +/- 54 microU/ml (n = 15), mean +/- SD plasma beta-hydroxybutyrate concentration was 1.8 +/- 1.2 mg/dl (n = 21), and mean +/- SD plasma nonesterified fatty acids concentration was 6.2 +/- 6.4 mg/dl (n = 21). None of the horses had hyperlipemia. Compared with clinically normal horses, horses with hyperadrenocorticism had increased lipolysis and increased ketogenesis. It was concluded that cortisol cannot be the sole factor contributing to insulin resistance in horses with hyperadrenocorticism.     

Association of vitamin K-dependent coagulation proteins and C4b binding protein with triglyceride-rich lipoproteins of human plasma

It has been proposed that females use the symmetry of secondary sexual traits to differentiate between potential mates. The vertical bars on male swordtail fish function as a signal that attracts females and deters rival males in one swordtail species. In addition, male courtship behaviour of most Xiphophorus species incorporates serial lateral presentations, which provide females with a clear opportunity to assess males for bilateral symmetry. We tested the hypothesis that X. cortezi females prefer males with a symmetrical bar number by determining whether females switched their preference between two males when we switched which male had a symmetrical number of bars. The ability to manipulate the bars without influencing other male traits allowed us to control for male characters correlated with bar symmetry that females might prefer. The degree of asymmetry in bar number we used was within the degree of asymmetry found for this trait in nature. Females switched their preference between a pair of males when we switched which male was symmetrical for bar number. We discuss the possibility that females prefer a symmetrical bar number as well as an alternative hypothesis. Copyright 1998 The Association for the Study of Animal Behaviour.     

Exercise studies in horses: 2. The cardiac response to exercise in normal horses and in horses with chronic obstructive pulmonary disease

The relationship of velocity (v) to heart rate (HR)and of kinetic energy (KE) to heart rate, were investigated in 6 normal horses and in 6 horses with chronic obstructive pulmonary, disease (COPD). Radiotelemetry was used to determine the heart rate while subjects were ridden on a 400m track. Velocity was measured by stop-watch between 2 markers 50 m apart at the end of the track. Kinetic energy was calculated from the formula KE =1/2 Mv2, where M = mass of horse, rider, saddle and bridle (KG) and V = velocity (metres per second). In all subjects, the relationship of velocity to heart rate was a linear one at each individual pace (i.e. walk, trot and gallop). There were however significant differences between the v/HR regression curves of each pace. These differences indicated that the increase in velocity per unit increase in heart rate was greater at the trot than at the walk, and greater at the gallop than at the trot. When data for all paces were combined, the relationship log v/log HR was a linear one. The above findings were also true of the relationship of kinetic energy to the heart rate. In horses, which reached maximal heart rate at a relatively low velocity, the v/HR curve became asymptotic. At comparable submaximal velocities, the heart rate of COPD subjects was approximately 20 beats per minute higher than that of normal subjects. This was also true when the term "kinetic energy per units mass" was substituted for velocity.     

Activation of coagulation and fibrinolysis in patients with abdominal true aortic aneurysm associated with disseminated intravascular coagulation

Two cases of abdominal true aortic aneurysm (AAA) associated with disseminated intravascular coagulation (DIC) were reported. Case 1 was an 81-year-old male who was admitted because of hematoma on the left leg and in whom was found by MRI an aortic aneurysm of 14 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia, hypofibrinogenemia and increased level of FDP. DIC was well controlled by surgical repair of the aneurysm after the administration of a small dose of heparin. Case 2 was a 60-year-old male who was admitted because of lumbago and hematoemesis and in whom was found by CT and echography an aortic aneurysm of 5.5 cm in diameter. Coagulation studies indicated DIC by revealing thrombocytopenia and an increased level of FDP. On the 2nd hospital day, he suddenly died due to the rupture of the aortic aneurysm. In most of 9 cases with AAA without DIC, plasma levels of thrombin-antithrombin III complex, plasmin-alpha 2 plasmin inhibitor complex and FDP-D dimer were also elevated. These findings indicate that the coagulation and fibrinolysis systems were generally activated in patients with AAA, and that DIC tends to occur in patients with a giant aortic aneurysm or an impending ruptured aneurysm.     

Reliability of using results of abdominal fluid analysis to determine treatment and predict lesion type and outcome for horses with colic: 218 cases (1991-1994)

OBJECTIVE: To assess clinical utility of abdominal fluid analysis in predicting outcome, lesion type, and whether medical or surgical treatment is indicated for horses with colic. DESIGN: Retrospective study. ANIMALS: 218 horses > 1 year old. PROCEDURE: Horses were classified on the basis of age, site of lesion, lesion type (nonstrangulating vs strangulating), type of treatment (medical vs surgical), and outcome (survival vs nonsurvival). Sensitivity and specificity of using age and results of abdominal fluid analysis, individually and in combination, to predict lesion type, type of treatment, and outcome were determined. RESULTS: Most single variables evaluated were found to have low sensitivity, specificity, and predictive value for determining lesion type, whether medical or surgical treatment was indicated, and outcome. When evaluated in series, abdominal fluid color and specific gravity had a high positive predictive value for lesion type, and patient age and abdominal fluid color had a high positive predictive value for outcome. CLINICAL IMPLICATIONS: Results of abdominal fluid analysis cannot be used alone to accurately predict lesion type, whether medical or surgical treatment is needed, or outcome for horses with colic.     

Infantile colic as maternal reason of consulting a pediatrician: characteristics of mother and child

About 10-20% of infants under four months of age suffer from infantile colic (IC), an excessive screaming behaviour caused by multiple factors. WESSELS et al. (1954) definition is that babies in usually good health and nutritional condition are screaming/whining more than three hours daily, more than three days weekly for no apparent reasons. The question is whether/in what way daily routines of infants concerned differ from normal infants. Mothers of colicky infants (n = 25) and mothers in a control group (n = 25) record characteristics of the mother/child relationship, their assumptions why the child is screaming, care and attention they provide and babies' reactions. For seven days the mothers kept a diary about the babies' behaviour and worked on questionnaires concerning social support received, depressant effects and exhaustion. Interviews about the extent of care provided as well as personal thoughts and emotions were conducted. The "colic group" formed two subgroups: one fulfilling Wessels criteria (Wessel-Koliker; WK), the other more conforming with the "control group" babies though mothers complained about screaming (Non-Wessel-Koliker; NWK). "Colic group"-babies received more attention and care (compared to the "control group" babies), attempts to calm them down frequently failed and mothers in this group reacted less promptly to their babies' screaming. "NWK-group"-mothers strongly tend to attribute the babies' screaming to "meteorism" or "discontent". No differences existed between groups concerning social support, depressant effects and exhaustion. There is a risk that the colic may negatively influence the mother/child interaction beyond three months.