Reference values for clinical chemistry tests during normal pregnancy.

OBJECTIVE: Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values. DESIGN: Longitudinal study of laboratory markers in normal pregnancies. SETTING: Uppsala University Hospital, Sweden. POPULATION: Healthy pregnant females. METHODS: We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7-17; week 17-24; week 24- 28; week 28-31; week 31-34; week 34-38; predelivery (0-2 weeks before delivery) and postpartum (> 6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. RESULTS: Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, gamma-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroid-stimulating hormone, urate and urea during these pregnancy periods. CONCLUSIONS: Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy.

Outcomes in Patients With Chest Pain Discharged After Evaluation Using a High-Sensitivity Troponin T Assay.

BACKGROUND: Most patients with chest pain are discharged from the emergency department (ED) with the diagnosis "unspecified chest pain." It is unknown if evaluation with a high-sensitivity troponin T (hsTnT) assay affects prognosis in this large population. OBJECTIVES: The aim was to investigate whether the introduction of an hsTnT assay is associated with reduced incidence of major adverse cardiac events (MACEs) and cardiovascular (CV) risk profile in patients with chest pain discharged from the ED. METHODS: The study included 65,696 patients with "unspecified chest pain" discharged from 16 Swedish hospital EDs between 2006 and 2013 in which an hsTnT assay was introduced as the clinical routine. Patients evaluated with a conventional and an hsTnT assay were compared regarding the occurrence of 30-day MACE and CV risk profile based on information from national registries. Patients directly discharged and those discharged after an initial admission were analyzed separately. RESULTS: Fewer directly discharged patients experienced a MACE when evaluated with an hsTnT compared with a conventional assay (0.6% vs. 0.9%; odds ratio [OR]: 0.7; 95% confidence interval [CI]: 0.57 to 0.83). In contrast, more patients discharged after an initial admission experienced a MACE when evaluated with an hsTnT (7.2% vs. 3.4%; OR: 2.18; 95% CI: 1.76 to 2.72). Admitted patients had a higher general CV risk profile when evaluated with hsTnT, whereas directly discharged patients had a lower general CV risk profile with the same test. CONCLUSIONS: Patients directly discharged from the ED with unspecified chest pain experienced fewer MACEs and had a better risk profile when evaluated with hsTnT. Our findings suggest that more true at-risk patients were identified and admitted. The implementation of hsTnT assays in Swedish hospitals has improved evaluations in the ED.

Treatment with combined oral contraceptives induces a rise in serum C-reactive protein in the absence of a general inflammatory response.

BACKGROUND: The role of inflammation in the pathogenesis of cardiovascular disease is well established. C-reactive protein (CRP) is the strongest independent predictor of myocardial infarction and stroke in women. Recent studies have indicated that CRP levels are raised during use of combined oral contraceptives (COCs). OBJECTIVES: The aim of the study was to investigate the effect of COCs on serum CRP levels and to indicate the underlying mechanisms of an expected increase. METHOD: In a prospective randomized cross over-study 35 women used two different preparations of COC, one second and one third generation. Serum levels of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), antibodies against oxidized LDL, insulin and insulin-like growth factor-I (IGF-I) along with insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 were analyzed before and during the two treatments. E-selectin, von Willebrand factor and factor VIII concentrations in plasma were also measured. RESULTS: A rise in serum CRP was observed during both treatments; the median level increased from 0.45 mg L(-1) at baseline to 1.48 mg L(-1) with second generation and to 2.02 mg L(-1) with third generation COC. The serum levels of SAA increased slightly during treatment with the third generation COC. IL-6 and TNFalpha were unaffected by treatment. Both preparations lowered IGF-I and raised IGFBP-1 and IGFBP-3 concentrations. CONCLUSION: The raised serum CRP concentration during treatment with COCs appears to be related to a direct effect on hepatocyte CRP synthesis and does not reflect IL-6 mediated inflammation, endothelial activation or induction of insulin resistance.

Serum S-100b protein as a prognostic marker in malignant cutaneous melanoma.

PURPOSE: To evaluate whether S-100B protein in serum is an independent prognostic marker in malignant melanoma. MATERIALS AND METHODS: S-100B protein in serum was analyzed in 1,007 consecutive patients with histologically verified cutaneous malignant melanoma. At the time of blood sampling, 876 patients were in clinical stage I, 35 were in stage II, and 96 were in stage III. The serum concentrations of S-100B protein were measured by a luminescence immunoassay (LIA). RESULTS: The mean serum concentration of S-100B protein was significantly related to clinical stage, with the lowest level in stage I and the highest in stage III. In a multivariate analysis, S-100B protein levels in serum showed the strongest prognostic impact of the factors analyzed with respect to disease-specific survival in clinical stages II to III, followed by clinical stage. Serum S-100B protein was not a significant independent prognostic factor in clinical stage I, where tumor thickness showed the strongest relation to melanoma-specific survival, followed by ulceration and satellites. CONCLUSION: This investigation contains the largest material of patients so far analyzed with the new LIA assay of S-100B protein in serum and confirms that S-100B protein in serum is correlated with clinical stage and is an independent prognostic marker in clinical stages II and III.

Evolution of differential substrate specificities in Mu class glutathione transferases probed by DNA shuffling.

A library of variant enzymes was created by combined shuffling of the DNA encoding the human Mu class glutathione transferases GST M1-1 and GST M2-2. The parental GSTs are 84 % sequence identical at the protein level, but their specific activities with the substrates aminochrome and 2-cyano-1,3-dimethyl-1-nitrosoguanidine (cyanoDMNG) differ by more than 100-fold. Aminochrome is of particular interest as an oxidation product of dopamine and of possible significance in the etiology of Parkinson's disease, and cyanoDMNG is a model for genotoxic and potentially carcinogenic nitroso compounds. GST M2-2 has at least two orders of magnitude higher catalytic activity with both of the substrates than any of the other known GSTs, including GST M1-1. The DNA library of variant Mu class GST sequences contained "mosaic" structures composed of alternating segments of both parental sequences. All clones contained the 5'-end of a GST M1-1 clone optimized for high-level expression in Escherichia coli. The remainder of the sequences derived from segments of GST M2-2 and GST M1-1 DNA. All of the clones analyzed contained between two and seven distinct DNA segments. In addition, each clone contained an average of approximately one point mutation. None of the library clones analyzed was identical with either of the two parental structures. Variant GST sequences were expressed in E. coli, and their enzymatic activities with aminochrome, cyanoDMNG, and 1-chloro-2,4-dinitrobenzene (CDNB) were determined in bacterial lysates. Such screening of more than 70 clones demonstrated a continuous range of activities covering at least two orders of magnitude for each of the substrates. For a given clone, the activities with aminochrome and cyanoDMNG, in spite of their different chemistries, were clearly correlated, whereas no strong correlation was found with CDNB. This functional correlation suggests a common structural basis for the enzymatic mechanisms for conjugation of aminochrome and denitrosation of cyanoDMNG. From an evolutionary perspective, the results show that recombination of segments from homologous proteins gives rise to a large proportion of functionally competent proteins with a range of activities. The data support the proposal that natural evolution of protein functions may involve recombination of DNA segments followed by selection for advantageous functional properties of the resulting proteins. Clearly, the same approach can be utilized in the engineering of proteins displaying novel functions by in vitro evolution.

Hypoalbuminemia in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Hypoalbuminemic patients admitted to the hospital for community-acquired pneumonia have increased mortality and morbidity. The aim of this study was to investigate the reasons for hypoalbuminemia in these patients. METHODS: During a 12-month period, all patients aged 50 to 85 years (with the exception of immunocompromised patients) with community-acquired pneumonia who were admitted to the Department of Infectious Diseases at Danderyd Hospital, Stockholm, Sweden, were included in a prospective study. The population studied consisted of 97 patients with a mean age of 69.6 years. The patients' nutritional status, including weight, history of weight loss, body mass index, and triceps skinfold thickness, was assessed on admission, as well as at two follow-up visits 8 weeks and 6 months after discharge from the hospital. Blood samples were drawn on admission, during the time in the hospital, and at the follow-up visits. Laboratory tests performed included the following: plasma proteins, albumin, transthyretin and transferrin, alpha 1-antitrypsin, orosomucoid, haptoglobin, C-reactive protein, and interleukin-6. RESULTS: No correlation was found between the serum albumin levels and the nutritional measurements. The serum albumin levels correlated positively with the transthyretin and transferrin levels, and inversely with the acute-phase proteins. CONCLUSIONS: The inflammatory reaction is the main reason for depressed serum albumin levels in elderly patients with pneumonia. The study results do not support the use of nutritional supplementation to alter the clinical outcome in these patients.

Elevated neopterin and beta 2-microglobulin levels in blood and cerebrospinal fluid occur early in HIV-1 infection.

Neopterin and beta 2-microglobulin (beta 2-M) concentrations in cerebrospinal fluid (CSF) and blood were measured in 56 individuals in various stages of HIV-1 infection. Elevated levels of neopterin as well as beta 2-M were found in the CSF of three patients with primary HIV-1 infection and also in subjects in the early stages of chronic HIV-1 infection, with the highest levels in HIV-1 isolation-positive people. There was a clear correlation between the concentrations of the two substances and the levels seemed to increase in parallel with progress of infection. A similar pattern was found in blood. Higher concentrations of neopterin and beta 2-M in CSF than in blood were found in patients with advanced dementia in particular. These findings indicate that the cellular immune system in the central nervous system (CNS) may be activated during the early stages of HIV-1 infection without concomitant overt neurological symptoms. The pathological processes in CNS and blood seem to develop in parallel rather than being restricted to one compartment.

Immunological changes in primary HIV-1 infection.

Homosexual men with symptomatic primary HIV-1 infection displayed a pronounced lymphopaenia with significantly depressed numbers of CD3+, CD4+ and CD8+ cells and B cells during the first week of illness. Subsequently, the CD8+ cell counts rose in parallel with numbers of CD3+ cells, atypical lymphocytes and activated (CD38+ and HLA-Dr+) cells to attain maximal levels about a month following onset of illness. In contrast CD4+ and B cell numbers remained low for an extended period of time. Early signs of a host response included a transient appearance of interferon-alpha in the blood and raised levels of neopterin and beta 2-microglobulin (beta 2-M). Neither CD4+/CD8+ cell ratio nor beta 2-M resumed completely normal values during a follow-up period of 2 years. These findings shed some light on pathogenetic events during early HIV-1 infection and suggest that the infection, following the acute symptomatic stage, usually enters a stage of chronic active rather than latent infection.

Structural determinants in domain II of human glutathione transferase M2-2 govern the characteristic activities with aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine, and 1,2-dichloro-4-nitrobenzene.

Two human Mu class glutathione transferases, hGST M1-1 and hGST M2-2, with high sequence identity (84%) exhibit a 100-fold difference in activities with the substrates aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine (cyanoDMNG), and 1,2-dichloro-4-nitrobenzene (DCNB), hGST M2-2 being more efficient. A sequence alignment with the rat Mu class GST M3-3, an enzyme also showing high activities with aminochrome and DCNB, demonstrated an identical structural cluster of residues 164-168 in the alpha6-helices of rGST M3-3 and hGST M2-2, a motif unique among known sequences of human, rat, and mouse Mu class GSTs. A putative electrostatic network Arg107-Asp161-Arg165-Glu164(-Gln167) was identified based on the published three-dimensional structure of hGST M2-2. Corresponding variant residues of hGSTM1-1 (Leu165, Asp164, and Arg167) as well as the active site residue Ser209 were targeted for point mutations, introducing hGST M2-2 residues to the framework of hGST M1-1, to improve the activities with substrates characteristic of hGST M2-2. In addition, chimeric enzymes composed of hGST M1-1 and hGST M2-2 sequences were analyzed. The activity with 1-chloro-2,4-dinitrobenzene (CDNB) was retained in all mutant enzymes, proving that they were catalytically competent, but none of the point mutations improved the activities with hGST M2-2 characteristic substrates. The chimeric enzymes showed that the structural determinants of these activities reside in domain II and that residue Arg165 in hGST M2-2 appears to be important for the reactions with cyanoDMNG and DCNB. A mutant, which contained all the hGST M2-2 residues of the putative electrostatic network, was still lacking one order of magnitude of the activities with the characteristic substrates of wild-type hGST M2-2. It was concluded that a limited set of point mutations is not sufficient, but that indirect secondary structural affects also contribute to the hGST M2-2 characteristic activities with aminochrome, cyanoDMNG, and DCNB.

Increased plasma fibrin gel porosity in patients with Type I diabetes during continuous subcutaneous insulin infusion.

BACKGROUND: Patients with Type 1 diabetes have a tighter plasma fibrin gel structure, to which impaired glycemic control might contribute. Improved glycemic control can be achieved with continuous subcutaneous insulin infusion (CSII). OBJECTIVES: The aim of the present study was to investigate the effect of CSII on plasma fibrin gel properties and circulating markers of inflammatory activity in patients with Type 1 diabetes. PATIENTS AND METHODS: Twenty-eight patients were investigated before and after 4-6 months' treatment with CSII. Fibrin gel structure formed in vitro from plasma samples was investigated by liquid permeation of hydrated fibrin gel networks. P-fibrinogen was analyzed by a syneresis method. Comparisons were made between patients with improved (> 0.5%) and unchanged (< 0.5%) glucosylated hemoglobin (HbA1c) during CSII. RESULTS: Eighteen patients showed improved and 10 patients unchanged HbA1c during CSII. P-fibrinogen, high sensitive C-reactive protein and serum amyloid A-antigen were not significantly changed, while fibrin gel permeability (Ks) and fiber mass-length ratio ( micro ) increased in both groups (P < 0.02). P-insulin and triglycerides decreased (P < 0.05) in both groups, while reductions of total cholesterol and intercellular adhesion molecule-1 were seen only in patients with improved HbA(1c) (P < 0.05). Absolute changes in Ks were inversely correlated to changes in plasma fibrinogen (r = 0.50; P < 0.01) and in LDL-cholesterol (r = 0.46; P < 0.05). CONCLUSIONS: Treatment with CSII in patients with Type 1 diabetes is associated with increased plasma fibrin gel porosity. Slight attenuation of the inflammatory activity was also observed. The changes in fibrin gel porosity seem to be mainly mediated by changes in plasma fibrinogen and blood lipids, and are probably secondary to improved insulin sensitivity.

Quantitation of C-reactive protein in cerebrospinal fluid and serum by zone immunoelectrophoresis assay (ZIA).

The zone immunoelectrophoresis assay (ZIA) for C-reactive protein (CRP) determinations is easy to perform and requires only small amount of antiserum, e.g., 25-100 and 0.5-1.0 microliter anti-CRP antibody/20 serum and CSF samples, respectively. For quantitating CSF-CRP the immunoprecipitates formed were stained using alkaline phosphatase-conjugated secondary antibodies and the lowest standard concentration used was 30 micrograms/l. The immunoprecipitates formed when measuring CRP in serum were stained by Coomasie brilliant blue R250 with a detection limit of about 300 micrograms/l. CRP was determined in cerebrospinal fluid in 27 patients with bacterial meningitis (range less than 0.03-23.0 mg/l) and in 25 patients with viral meningitis (range less than 0.03-0.23 mg/l). CRP was quantitated in 52 sera by both the CRP ZIA method (y) and by electroimmunoassay (x). The correlation coefficient was r = 0.992 with the regression line y = 1.024 x + 0.855.

On the quantitative structure-activity relationships of meta-substituted (S)-phenylpiperidines, a class of preferential dopamine D2 autoreceptor ligands: modeling of dopamine synthesis and release in vivo by means of partial least squares regression.

The quantitative structure-activity relationship between physicochemical properties and effects on dopamine (DA) synthesis and release in the rat brain, in a series of meta-substituted (S)-phenylpiperidines, has been investigated by means of partial least squares regression (PLS). The effect on DA synthesis caused by the drugs, in both non-pretreated and reserpine-pretreated rats, was assessed by measurements of tissue levels of L-DOPA accumulated in the striatum following treatment with a decarboxylase inhibitor. Assessment of effects on DA release was performed by analysis of perfusates collected from implanted microdialysis probes. The numerical characterization of the variation in physicochemical features of the phenylpiperidines used in the regression modeling was accomplished by using common tabulated aromatic and aliphatic substituent constants in combination with a set of property descriptors derived from molecular mechanics and semiempirical calculations. It was found that the biochemical responses could be accurately predicted by the regression models based on these molecular feature measures. The molecular features exerting influence on DA synthesis were found to be markedly different from those influencing DA release. This finding is discussed in terms of the possible existence of a dopamine receptor-mediated DA release-controlling mechanism, which may not involve the synthesis regulating DA D2 autoreceptor. Some findings regarding the impact of the piperidine N substituent on agonist properties of the drugs are reported. The regression models were also used for guidance in the search for a phenylpiperidine with a lower intrinsic activity, at the DA D2 type autoreceptor, than the partial DA agonist preclamol (3).

Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H-benz[e]indole ring system. 1. Effects of substituents in the aromatic system on serotonin and dopamine receptor subtypes.

A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but many of the compounds displayed higher affinities for 5-HT1D alpha than for 5-HT1D beta receptors.

Plasma levels of von Willebrand factor and fibronectin as markers of persisting endothelial damage in preeclampsia.

OBJECTIVE: To evaluate the levels of von Willebrand factor and fibronectin as markers for the severity of endothelial cell injury in preeclampsia. METHODS: In 63 pregnant women with preeclampsia, the plasma levels of von Willebrand factor and fibronectin were measured as soon as symptoms were detected, at 5 weeks postpartum, and after lactation. They were also compared with levels in 29 normotensive pregnant women. The von Willebrand factor was measured by enzyme-linked immunoassay and fibronectin was measured using an automated immunonephelometric method. RESULTS: In preeclampsia, the levels of von Willebrand factor and fibronectin were higher than in normal pregnancy samples drawn in the second and third trimesters. The levels of fibronectin were still elevated at 5 weeks postpartum in women with severe preeclampsia. Four patients with severe preeclampsia who were studied frequently had high levels of von Willebrand factor 5 weeks postpartum. CONCLUSIONS: The increased maternal plasma levels of von Willebrand factor and fibronectin indicate that endothelial stimulation is present during preeclampsia. The high fibronectin values found even 5 weeks after delivery, at least in patients with severe preeclampsia, may indicate an ongoing vascular disease with increased risk for preeclampsia in subsequent pregnancies.

Release of S100B during coronary artery bypass grafting is reduced by off-pump surgery.

BACKGROUND: S100B, a plasma marker of brain injury, was compared after coronary artery bypass grafting with and without cardiopulmonary bypass (CPB). METHODS: Fourteen patients with off-pump operations and 18 patients with CPB were compared. Seven patients in the off-pump group underwent a minithoracotomy and received only an arterial graft, whereas 7 patients underwent sternotomy and received both an arterial and one or two vein grafts. S100B was measured in arterial plasma using an immunoassay with enhanced sensitivity. RESULTS: S100B before the operation was 0.03 microg/L. At wound closure, S100B in patients of the off-pump and CPB groups reached a maximum level of 0.22 +/- 0.07 and 2.4 +/- 1.5 microg/L, respectively (p < 0.001). No strokes occurred. Patients without CPB receiving arterial and vein grafts released slightly more S100B (p < 0.05) than patients with only arterial grafting. In patients undergoing CPB, S100B increased slightly before aortic cannulation (p < 0.001), to the same level as the maximum reached for the non-CPB group. CONCLUSIONS: Coronary artery bypass grafting with CPB caused a 10-fold greater increase in S100B than off-pump grafting. S100B release after off-pump sternotomy with vein grafting was slightly greater than in arterial grafting through a minithoracotomy.

The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass.

BACKGROUND: An increase of S100beta in serum during cardiopulmonary bypass (CPB) has been interpreted as a sign of brain injury. Cardiotomy suction may cause fat embolization, and its role in the S100beta increase was examined. METHODS: Twenty coronary artery operation patients were randomly assigned to two groups, 10 with suction during CPB to cardiotomy reservoir (CR), 10 to cell saving device (CS). S100beta was measured (immunoassay) in blood from the patients and from cell saving device after processing. In 7 additional patients S100beta was measured in the cell saving device before processing and directly from the wound at sternotomy. RESULTS: Before anesthesia, serum S100beta was 0.03+/-0.06 microg/L. At the end of CPB it was 2.47+/-1.31 microg/L and 0.44+/-0.27 microg/L (CR vs CS; p < 0.001). S100beta was 33+/-12 microg/L in CS reservoir and 42+/-18 microg/L in blood from the wound. CONCLUSIONS: Most serum S100beta after CPB with cardiotomy suction may be of extracerebral origin. S100beta after CPB with cell saving device was the same as after off-pump operation. The interpretation that an increase in S100beta during CPB in patients reflects cerebral injury must be questioned.

Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources.

BACKGROUND: Elevated levels of serum S100B after coronary artery bypass grafting may arise from extracerebral contamination. Serum S100B content was analyzed in several tissues, and the two dimers S100A1-B and S100BB were analyzed separately in blood. METHODS: Serum, shed blood, marrow, fat, and muscle were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass using suction either to the cardiotomy reservoir (group 1, n = 10) or to a cell-saving device (group 2, n = 10), or operated on off-pump (group 3, n = 10). RESULTS: Serum S100B was sixfold higher in group 1 than in groups 2 and 3, which were identical. The same ratio between S100A1-B and S100BB was found in all groups. When compared with serum, S100B was 10(2) to 10(4) times higher in marrow, fat, muscle tissue, and shed blood. CONCLUSIONS: Separate analysis of S100A1-B and S100BB did not distinguish between S100B of cerebral and extracerebral origin. The concept that S100B only originates in astroglial and Schwann cells is wrong. Fat, muscle, and marrow in mediastinal blood contain high levels of S100B. Cardiopulmonary bypass caused no increase in S100B.

Acute dopaminergic influence on plasma adrenaline levels in the rat.

This study was aimed at in vivo characterisation of the possible role of dopamine receptors in the modulation of adrenaline release from the adrenal medulla in rats. Quinpirole (0.3, 1 and 3 mg/kg s.c., 30 min), an agonist at dopamine D2-like receptors induced a statistically significant increase not only in adrenal dopamine but also in plasma and heart adrenaline levels. The effects of the lowest dose of quinpirole were blocked by domperidone (5 mg/kg s.c., 150 min). Implantation of catheters followed by blood sampling appeared to be a stressful procedure, inducing itself an elevation of adrenal dopamine and of heart adrenaline by 100 and 250%, respectively. To explore the possibility of determining the plasma levels of adrenaline without blood sampling, regression modelling was performed by means of partial least squares regression (PLS) using treatment and levels of heart adrenaline and adrenal dopamine as predictor variables. The selected variables were found to be good predictors of plasma adrenaline levels. Accordingly, the increase in adrenal dopamine and heart adrenaline levels following administration of the dopamine autoreceptor agonist, talipexole, and the classical non-selective dopamine receptor agonist, apomorphine, were interpreted as indicators of the increased adrenomedullary adrenaline release. Neither of the dopamine D2 receptor antagonists used, i.e. domperidone, supposed to have only peripheral effects, nor raclopride, had significant effects on adrenal dopamine and heart adrenaline. Our results support the presence of peripherally located dopamine D2-like receptors, capable of acutely stimulating not only the synthesis of catecholamines, but also the release of adrenaline from adrenals in the conscious rat.

High serum S100B levels for trauma patients without head injuries.

OBJECTIVE: Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS: A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS: The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION: Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.

Insulin lispro therapy in pregnancies complicated by type 1 diabetes mellitus.

OBJECTIVE: To compare the efficacy and safety of preprandial administration of rapid-acting lispro analogue with regular short-acting insulin to pregnant women with type 1 diabetes. STUDY DESIGN: Open randomised multicentre study. Women were treated with multiple insulin injections aiming at normoglycaemia. Blood glucose was determined six times daily, HbA(1c) every 4 weeks. Diurnal profiles of blood glucose were analysed at gestational week 14 and during the study period at weeks 21, 28 and 34. PARTICIPANTS: 33 pregnant women with type 1 DM were randomised to treatment with lispro insulin (n=16) or regular insulin (n=17). RESULTS: Blood glucose was significantly lower (P<0.01) after breakfast in the lispro group, while there were no significant group differences in glycemic control during the rest of the day. Severe hypoglycaemia occurred in two patients in the regular group but biochemical hypoglycaemia (blood glucose <3.0 mmol/l) was more frequent in the lispro than in the regular group (5.5 vs. 3.9%, respectively). HbA(1c) values at inclusion were 6.5 and 6.6% in the lispro and regular group respectively. HbA(1c) values declined during the study period and were similar in both groups. There was no perinatal mortality. Complications during pregnancy, route of delivery and foetal outcome did not differ between the groups. Retinopathy progressed in both groups, one patient in the regular group developed proliferative retinopathy. CONCLUSION: The results suggest that it is possible to achieve at least as adequate glycemic control with lispro as with regular insulin therapy in type 1 diabetic pregnancies.