Prolactin is involved in the systemic inflammatory response in myocardial infarction.

Prolactin may contribute to an atherogenic phenotype. Furthermore, previous studies have shown that prolactin levels increase in situations of acute stress and inflammation. We therefore aimed to investigate the relationship between prolactin, acute stress and inflammation in patients with myocardial infarction. We performed a case-control study in 40 patients with myocardial infarction and 39 controls, aged 41-84 years. Blood for assessment of prolactin and high sensitive C-reactive protein (hsCRP) was drawn at inclusion, that is, during the acute phase of the event, and 2-3 weeks later. Unexpectedly, prolactin levels at inclusion did not differ between cases and controls (7.0 ng/ml and 6.0 ng/ml, respectively, p=0.28). 2-3 weeks later prolactin levels in cases had not decreased. However, univariate regression analysis indicated that hsCRP is associated with prolactin levels (regression coefficient ß 0.11; [95% CI 0.01; 0.21]; p=0.03) in cases during the acute phase of myocardial infarction. Our findings may suggest that prolactin is involved in the systemic inflammatory response, which takes place during myocardial infarction; however, this association may not be strong enough to induce higher prolactin levels in patients with myocardial infarction.

Procalcitonin as a potent marker of bacterial infection in febrile Afro-Caribbean patients at the emergency department.

Procalcitonin (PCT) has been shown to be of additional value in the work-up of a febrile patient. This study is the first to investigate the additional value of PCT in an Afro-Caribbean febrile population at the emergency department (ED) of a general hospital. Febrile patients were included at the ED. Prospective, blinded PCT measurements were performed in patients with a microbiologically or serologically confirmed diagnosis or a strongly suspected diagnosis on clinical grounds. PCT analysis was performed in 93 patients. PCT levels differentiated well between confirmed bacterial and confirmed viral infection (area under the curve [AUC] of 0.82, sensitivity 85%, specificity 69%, cut-off 0.24 ng/mL), between confirmed bacterial infection and non-infectious fever (AUC of 0.84, sensitivity 90%, specificity 71%, cut-off 0.21 ng/mL) and between all bacterial infections (confirmed and suspected) and non-infectious fever (AUC of 0.80, sensitivity 85%, specificity 71%, cut-off 0.21 ng/mL). C-reactive protein (CRP) levels were shown to be less accurate when comparing the same groups. This is the first study showing that, in a non-Caucasian febrile population at the ED, PCT is a more valuable marker of bacterial infection than CRP. These results may improve diagnostics and eventually decrease antibiotic prescriptions in resource-limited settings.

Soluble tissue factor is a candidate marker for progression of microvascular disease in patients with Type 2 diabetes.

OBJECTIVE: To determine the relationship between abnormalities in blood coagulation and prevalent or incident cardiovascular complications in Type 2 diabetes. DESIGN AND METHODS: Prospective cohort study of 128 patients with Type 2 diabetes in whom blood samples were collected at baseline and after 1 year of follow-up. All cardiovascular complications at baseline and follow-up were recorded. Forty-three healthy, age-matched subjects served as a control group. RESULTS: Logistic analysis revealed an independent relationship between soluble tissue factor (TF) and microvascular disease [per pg mL(-1) TF: Exp(B) = 1.008; CI(95%)1.002-1.014], or neurogenic disease [Exp(B) = 1.006; CI(95%)1.001-1.011]. The highest levels of soluble TF were observed in patients with microvascular and neurogenic disease (P < 0.001). Patients with Type 2 diabetes having a soluble TF concentration >300 pg mL(-1) are at a 15-fold higher risk for the presence of microvascular disease and at a 10-fold higher risk for the presence of neurogenic disease compared with the patients with concentrations below 100 pg mL(-1). Soluble TF was correlated with tissue type plasminogen activator, von Willebrand factor antigen, systolic blood pressure and age. Levels of F1' + 2, D-dimer, FVIII activity, t-PA and vWFag were not different among patients with micro-, macro- or neurogenic complications compared with patients without those complications. Forty-eight new micro-, macro- and/or neurogenic complications were diagnosed after 1 year follow-up. With the exception of higher F1 + 2 levels after 1 year all other markers remained unchanged. A trend toward higher soluble TF levels was observed in patients with new microvascular events (P = 0.056). CONCLUSIONS: Soluble TF is associated with existing microvascular and neurogenic complications in patients with Type 2 diabetes and is a candidate marker for progression of microvascular disease.

Mast cell mediator tryptase levels after inhalation or intravenous administration of high doses pharmaceutically prepared heroin.

BACKGROUND: Opioids like morphine and heroin induce mast cell degranulation in vitro. The release of mast cell mediators like histamine and tryptase may lead to allergic symptoms. In this study it was investigated whether mast cell mediator release also occurs in vivo in addicted patients who participated in a heroin on medical prescription trial, and were under treatment with large doses of heroin in combination with methadone. METHOD: Plasma levels of tryptase, a specific marker for mast cell degranulation, were measured by immuno-assay at baseline and 60 min after heroin administration. Heroin was administered either by intravenous injection (11 subjects) or by inhalation (nine subjects). Single heroin doses varied from 200 to 450 mg. Besides tryptase, the plasma concentrations of heroin, its metabolite morphine and methadone were measured. RESULTS: After heroin injection, the mean tryptase plasma concentration increased dose dependently by on average 23.1% (95% CI 14.6-31.6%). After heroin inhalation, no tryptase release was observed. Heroin and morphine peak plasma concentrations were 3-5 times greater in heroin injectors than in inhalers. In heroin injectors, tryptase levels were related to morphine peak concentrations, but not to heroin concentrations. Tryptase plasma concentrations were not related to methadone levels. Mild allergic reactions were reported in five cases after intravenous heroin use, but not after inhalation. CONCLUSION: This study revealed that mast cell mediator tryptase concentrations increase after intravenous heroin injection in chronic opioid users, but not after heroin inhalation. This may be explained by the higher Cmax levels of metabolite morphine that were achieved after injection than after inhalation. Although statistical significance was reached, the degree of mast cell degranulation after intravenous injection of heroin was mild, and did not lead to clinically relevant side effects in this group of opioid-tolerant subjects.

Cerebrospinal fluid carcinoembryonic antigen in patients with metastatic and nonmetastatic neurological diseases.

Cerebrospinal fluid (CSF) carcinoembryonic antigen (CEA) values were determined in 200 patients suffering from various neurological diseases. We found no relationship between CEA levels and age or sex. A positive test was defined as an upper limit of at least 4.0 ng/mL of CEA. We found raised CSF CEA levels in patients with leptomeningeal spread from carcinoma, but not in patients with leptomeningeal metastases from lymphoma. We also found high values of CSF CEA in three of 21 patients with epidural metastases and in two of 28 patients with cerebral metastases from solid tumors. Comparison was made with the CSF levels of total protein, glucose, and lactate dehydrogenase. The sensitivity of the CSF CEA determination in patients for the presence of leptomeningeal involvement of cancer is 31% and the specificity is 90%.

The abnormal lipid spectrum in malignant obstructive jaundice in relation to endotoxin sensitivity and the result of preoperative biliary drainage.

BACKGROUND: Biliary obstruction changes the spectrum of lipoproteins, which are now known to bind and neutralize endotoxin. Postoperative septic complications related to an increased susceptibility to endotoxin occur frequently in patients with obstructive jaundice. The effect of preoperative biliary drainage on changes in the lipoprotein spectrum and its relation to endotoxin sensitivity was studied. METHODS: Abnormalities in the lipoprotein spectrum were assessed in 15 patients with malignant obstructive jaundice before and 3 weeks after endoscopic biliary drainage. Changes in endotoxin responsiveness were assessed by using endotoxin-neutralizing reagents (anti-CD14 monoclonal antibody, polymyxin B, and recombinant bactericidal permeability increasing protein) to block cytokine production in whole blood cell cultures that were stimulated by cholestatic plasma taken before and after drainage. RESULTS: Drainage normalized very-low-density, low-density, and high-density lipoprotein cholesterol fractions from, respectively, 43% to 19%, 50% to 65%, and 6% to 16% (P <.01). Ex vivo stimulation of whole blood with predrainage cholestatic plasma was 20-fold higher (P <.001) than with postdrainage plasma. Blocking the endotoxin response during the stimulation with predrainage cholestatic plasma with anti-CD14 monoclonal antibody, polymyxin B or recombinant bactericidal permeability increasing protein resulted in attenuation of the inflammatory response, reducing tumor necrosis factor-alpha levels at least 5-fold. CONCLUSIONS: Preoperative biliary drainage normalizes the changed lipid profile and the endotoxin-stimulating capacity of cholestatic plasma, and this signifies a change in sensitivity to endotoxin.

Erythrocyte transketolase, a new semi-automated method.

This paper describes a method to determine transketolase activity in erythrocytes, with or without addition of thiamine-pyrophosphate, by quantitating the formation of glucose-6-phosphate forming during the incubation of hemolysed blood with ribose-5-phosphate. Glucose-6-phosphate is determined enzymatically, after deproteinisation of the sample, using a centrifugal fast analyser. The proposed method gave a correlation of r = 0.89 with an accepted colorimetric method. Reference values for blood are in the range 32--101 U/l.

Cerebrospinal fluid lactate dehydrogenase activities in patients with central nervous system metastases.

Lactate dehydrogenase activities were determined in CSF from 350 patients suffering from various neurological diseases. Reference values were established as 0-26 U/l. Slight elevations of CSF LDH activities were observed in patients with the following disorders: brain metastasis and spinal epidural metastasis from solid carcinomas, primary central nervous system tumours, cerebrovascular accident, polyneuropathy and head injury. Marked elevations were observed incidentally in patients in these groups and in a considerable number of patients with bacterial meningitis and with leptomeningeal spread from solid or haematologic malignancies. When other diagnostic information is available for the proper estimation of the pre-test likelihood of disease, CSF LDH activities exceeding 50 U/l are suggestive for meningeal carcinomatosis.

Improved extraction procedure for determination of bile acids in faeces.

A simplified extraction procedure for bile acids from wet faeces, using methanol/hydrochloric acid is described. Extracts were analyzed by gas-liquid chromatography, thin-layer chromatography and an enzymatic assay, with 3 alpha-hydroxysteroid dehydrogenase. Recoveries of some stable bile acids, added to faeces, were studied; extraction efficiency was also investigated with a procedure using radioactive labelled bile acids given orally to patients. Resin treatment of faecal extracts, because of the sometimes hard colour of the extracts, resulted in a slightly lower recovery as determined by the enzymatic method. Recoveries were higher, using the proposed extraction procedure, than those obtained with extracts prepared by the standard procedure of Grundy et al [6].

Tumour markers in the cerebrospinal fluid of patients with central nervous system metastases from extracranial malignancies.

We have assessed the diagnostic value of the determination of cerebrospinal fluid lactate dehydrogenase, carcinoembryonic antigen, beta 2-microglobulin, beta-glucuronidase and total protein, using linear discriminant analysis, in detecting central nervous system metastases from extracranial malignancies. We conclude that, using these tests, it is impossible to differentiate between control individuals and patients with brain or epidural metastases. Leptomeningeal dissemination from either solid tumours or non-Hodgkin lymphoma could be differentiated from control individuals and patients with brain or epidural metastases. In this differentiation it is essential that bacterial, fungal or tuberculous meningitis be excluded from the differential diagnosis by other diagnostic procedures. The combination of beta-glucuronidase and beta 2-microglobulin provides almost the same diagnostic information as the combination of all parameters.

Cerebrospinal fluid beta-glucuronidase activities in patients with central nervous system metastases.

beta-Glucuronidase activities were determined in cerebrospinal fluid from 249 patients suffering from various neurological diseases. Reference values were established as 9-27 mU/l. Marked elevations of cerebrospinal beta-glucuronidase activities were observed in patients with bacterial and carcinomatous meningitis. Slight elevations of cerebrospinal beta-glucuronidase activities were observed in epidural and parenchymal metastases from solid tumours. Comparison was made with the determination of total protein, glucose and lactate dehydrogenase in cerebrospinal fluid. Cerebrospinal beta-glucuronidase activity appeared the most useful test in monitoring patients at risk in developing meningeal metastases from solid primary tumours.

Gentamicin assay: comparison of an adapted EMIT method and an RIA method.

The EMIT technique for gentamicin assay adapted to the Centrifichem-300 system was compared with an established RIA procedure. EMIT results correlated very well with the results obtained by the RIA method (r = 0.976, N = 48). For the adapted EMIT assay, the interassay coefficient of variation was 4-8% and for the RIA method 6-14%. Several possible interfering agents were investigated, of which only carbenicillin showed interference in both assays. Our data indicate that the EMIT technique exhibits adequate precision and accuracy for routine gentamicin determinations.

Diagnosis of leptomeningeal metastasis.

Forty-one cases of leptomeningeal metastases from solid and hematological tumours were studied clinically and pathologically. Neurological symptoms and signs, cerebrospinal fluid characteristics and radiographic appearance were reviewed. The role of the biochemical markers, computer tomography scans of the brain and myelography in the diagnosis of patients with leptomeningeal metastasis were determined. The subject of the study was an investigation of the value of various diagnostic procedures to increase the accuracy of the diagnosis leptomeningeal metastasis.

High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study.

BACKGROUND: Thyroid hormone affects the coagulation system, but its effect on clinical disease is not clear. We determined the associations of levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase antibodies (antiTPO) with levels of coagulation factors and the risk of venous thrombosis. METHODS: In a large population based case-control study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study) on the etiology of venous thrombosis, we determined the levels of FT4, TSH, antiTPO, factor FII, FVII, FVIII, FIX, FX, von Willebrand factor (VWF), antithrombin, protein C, protein S and fibrinogen in 2177 cases and 2826 controls. RESULTS: High levels of FT4 were associated with increased concentrations of procoagulant factors, and not with levels of anticoagulant factors. High levels of FT4 were also associated with the risk of venous thrombosis, up to an odds ratio (OR) of 2.2 (95% confidence interval [CI] 1.0-4.6) for levels above 24.4 pm relative to FT4 levels between 15.5 and 18.9 pm. In 11 cases and one control, clinical hyperthyroidism had been diagnosed within a year of the thrombotic event, leading to an OR of 17.0 (95% CI 2.2-133.0) for thrombosis. The ORs approached unity after adjustment for FVIII and VWF, which suggests that the effect was mediated by these factors. Low TSH levels were also, but less evidently, associated with thrombosis, whereas there was no association between antiTPO and venous thrombosis risk. CONCLUSIONS: High levels of FT4 increase the concentrations of the procoagulant proteins FVIII, FIX, fibrinogen, and VWF, and by this mechanism increase the risk of venous thrombosis.

Alterations in coagulation and fibrinolysis after levothyroxine exposure in healthy volunteers: a controlled randomized crossover study.

BACKGROUND: Several hemostatic abnormalities have been reported in hyperthyroidism, but the overall effect of thyroid hormone excess on coagulation and fibrinolysis is unclear. OBJECTIVE: Our aim was to assess whether the use of supraphysiological doses of levothyroxine leads to coagulation activation and inhibition of fibrinolysis. PATIENTS AND METHODS: Healthy volunteers were randomized to receive levothyroxine or no medication for 14 days with a washout period of at least 28 days in a crossover design. To study the effects of different degrees of thyroid hormone excess, 16 participants received levothyroxine in a dose of 0.3 mg per day, and 12 received levothyroxine 0.45 or 0.6 mg per day depending on body weight. Several variables of coagulation and fibrinolysis were measured. RESULTS: Levels of von Willebrand factor activity (VWF:RiCo) and antigen (VWF:Ag), factor (F) VIII, plasminogen activator inhibitor-1 (PAI-1) and clot-lysis time were slightly higher after levothyroxine 0.3 mg per day than after the control situation, but only levels of VWF showed a significant increase from baseline. After levothyroxine 0.45 or 0.6 mg per day, levels of fibrinogen increased by 17%, VWF activity by 24%, VWF antigen by 26%, FVIII by 19%, FIX by 14%, FX by 7%, PAI-1 by 116% and clot-lysis time by 14%, and activated partial thromboplastin time decreased by 3%; all were significant changes compared with the control situation. We did not observe clear evidence of coagulation activation. CONCLUSIONS: Our data suggest that thyroid hormone excess increases coagulation factor levels and inhibits fibrinolysis in a dose-dependent fashion. This implies an increased risk of venous thrombosis during hyperthyroidism.

Conductometric titration of hydrochloric acid in gastric juice.

We describe a procedure for the determination of hydrochloric acid concentration in gastric juice by means of a conductometric titration of the 50-fold diluted sample with an aqueous ammonia solution. The conductometric method of endpoint indication leads to a definite location of the equivalence point in the titration of hydrochloric acid. The proposed method is simple and accurate and shows a good correlation with an accepted method for the measurement of gastric acidity.

Direct kinetic method for the determination of phosphate.

Serum phosphate can be measured accurately, precisely and economically using an initial rate spectrophotometric procedure. This procedure measures the formation of the unreduced phosphomolybdate heteropolyacid complex at 334 nm. The concentration of polyvinylpyrrolidone Mr = 40,000 has been optimised to allow the determination of serum inorganic phosphate on a discrete analyser, the Eppendorf Epos. Possible interference due to hyperlipaemia, high bilirubin or high protein content of the serum samples is discussed.

Interferences in current methods for measurements of creatinine.

We measured the interference of carbonyl compounds, drugs, and other substances in human serum on the determination of creatinine by the two-point, fixed-time kinetic modification of the Jaffé reaction as well as by four enzymatic methods. We added known concentrations of the interfering substances to a solution of creatinine in water. For bilirubin, we used both pooled normal sera with added bilirubin and icteric patient sera. The magnitude of interferences varies widely from method to method. Carbonyl compounds, dopamine, cephalosporines, and bilirubin interfere with the Jaffé reaction. Bilirubin, creatine, dopamine, ascorbic acid, and sarcosine interfere with the enzymatic methods. We conclude that the elimination of interferences in the determination of creatinine has still not been achieved.

Clinical implications of differences between two recommended procedures for determination of aspartate aminotransferase.

We compared two officially recommended methods for determination of aspartate aminotransferase (EC 2.6.1.1): that of the International Federation of Clinical Chemistry (IFCC) and that of the Deutsche Gesellschaft für Klinische Chemie (DGKC). We used automated enzyme analyzers, initiating the reactions with 2-oxoglutarate. Normal values, 10-30 U/L (IFCC) and 7-18 U/L (DGKC), were apparently insensitive to intra-individual variations. Samples obtained from patients with heart disease showed a markedly different amount of activation with pyridoxal phosphate as compared with samples from other patient categories. Ratios for aspartate aminotransferase/alanine aminotransferase, as used in the differentiation of liver disease, can still be used with either method for determination of aspartate aminotransferase.