Vasoactive substances in early dumping syndrome: effects of dumping provocation with and without octreotide

In patients after gastric surgery, early dumping symptoms can be provoked by oral glucose challenge. Octreotide effectively prevents the occurrence of dumping symptoms. We have studied plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP) concentrations in nine patients with early dumping, 10 surgical control subjects and nine healthy control subjects after an oral glucose challenge preceded by either placebo or 25 μg of octreotide subcutaneously (s.c.). In the dumping group, basal PRA was signifi-cantly ( P  < 0.01) higher (3.9 ± 0.6 μg L⁻¹ h⁻¹) than in either surgical or healthy control subjects (1.1 ± 0.3 μg L⁻¹ h⁻¹ and 1.1 ± 0.2 μg L⁻¹ h⁻¹ respectively) and showed a significant rise after glucose ingestion to 5.4 ± 0.9 μg L⁻¹ h⁻¹ that did not occur in control subjects. Aldosterone concentration showed a concomitant rise. In dumping patients, plasma ANP decreased after glucose ingestion from 31 ± 6 ng L⁻¹ to 21 ± 5 ng L⁻¹ ( P  < 0.05). This decrease did not occur in control subjects. Early dumping is associated with an activation of the renin–aldosterone axis and a decrease in plasma ANP, reflecting a hypovolaemic state. Octreotide prevents the occurrence of these changes.     

The promoting effect of epinephrine on lipopolysaccharide-induced interleukin-8 production in whole blood may be mediated by thromboxane A2

Summary.  Epinephrine is known to enhance lipopolysaccharide (LPS)-induced interleukin (IL)-8 secretion in a platelet dependent manner. To determine whether thromboxane A₂ (TxA₂; a product from activated platelets) is involved in this process, blood samples drawn either before or 2 h after oral administration of 440 mg acetylsalicylic acid (ASA) were stimulated with LPS (5 ng mL⁻¹) and different concentrations of epinephrine were added (0.1–100.0 µmol L⁻¹). ASA ingestion significantly (global P  < 0.05) reduced the enhancing effect of epinephrine on LPS-induced IL-8 release by 15–28%. To further explore whether TxA₂ may be involved in this process, a TxA₂ agonist (U46619) was added to whole blood together with LPS instead of epinephrine. U46619 mimicked the epinephrine effect: 20 ng mL⁻¹ U46619 enhanced LPS-induced IL-8 release by 39% ( P  < 0.05). Furthermore, preincubation of whole blood with 75 µmol L⁻¹ or 150 µmol L⁻¹ SQ29548, a TxA₂ receptor antagonist, completely blocked epinephrine's promoting effect on LPS-induced IL-8 release. Since thrombin-activated platelets have been reported to be important in the production of IL-8 in monocytes through the activation of monocytes by exposed RANTES in a P-selectin-dependent reaction, we suggest that the epinephrine effect is mediated by enhanced TxA₂ production and subsequent rise in the exposure of RANTES and P-selectin on the platelets of whole blood.     

The relationship of serum total sialic acid with serum acute phase proteins and lipoprotein (a) in patients with severe hypertriglyceridaemia

Abstract. Total serum sialic acid (TSA), recently shown to be a cardiovascular risk factor, was measured in 15 patients with severe hypertriglyceridaemia (fasting triglyceride > 2·3 mmol l^-1) and 15 age and sex matched normal control subjects.
To test the hypothesis that serum TSA is related in some way to serum acute phase proteins we also measured five acute phase proteins, namely alpha-1-antichymotrypsin (ACT), alpha-1-acid-glycoprotein (AGP), alpha-2-macroglobulin (AMG), C-reactive protein (CRP) and haptoglobin (HAP) in both groups.
Of note was the significantly elevated serum TSA in the severely hypertriglyceridaemic group as compared to normal subjects. Serum TSA being 71·9 ± 11·7 mg dl^-1 and 59·6 ± 10·2 mg dl^-1 respectively ( P < 0·01 Mann-Whitney test).
Serum CRP was significantly elevated in the type IV patients as compared to controls (6·4 ± 4·5 mg l^-1 vs. 3·3 ± 1·9 mg l^-1 P <0·05 Mann Whitney test) as was serum AMG (2·1 ± 0·89 g l^-1 vs. 1·5 ± 0·53 g l^-1 P < 0·05 Mann Whitney test).
There was no correlation between serum TSA and lipoprotein (a) in either the normal or severely hypertriglyceridaemic subjects. We suggest that serum TSA could in part be related to hypertriglyceridaemia and serum acute phase proteins but that its property as a cardiovascular risk factor is not related to serum lipoprotein (a) concentrations.     

Increased serum concentrations of the carboxy-terminal cross-linked telopeptide of collagen type I in patients with Gram-negative septicaemia

The authors determined serum levels of the carboxy-terminal cross-linked telopeptide and the carboxy-terminal propeptide of type 1 collagen (ICTP and PICP) in 18 patients with Gramnegative septicaemia before (day 0) and 28 days after therapy and in 18 age- and sex-matched controls by radioimmunoassay. Elevated levels of ICTP were observed in septicaemic patients [median (range): 15 (7–49) μg L⁻¹ before therapy and 14 (6–45) μg L⁻¹ 28 days after therapy vs. 2.1 (1.4–4.3) μg L⁻¹ in normal subjects; P  < 0.01 for both], whereas PICP levels were not different between patients and controls [median (range): 119 (52–275) μg L⁻¹ (day 0) and 133 (79–288) μg L⁻¹ (day 28) vs. 91 (54–213) μg L⁻¹ in normal subjects, P  > 0.05 for all]. The findings suggest an increased production or release of ICTP in Gram-negative septicaemia, presumably owing to an alteration of extracellular matrix during septicaemia-related vascular inflammation.     

Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis

Objective:  To evaluate the influence of obesity on pharmacokinetics of amiodarone (AMD) using Non-Linear Mixed Effects Modelling ( nonmem ) in Japanese patients treated with oral therapy.
Method:  Serum concentrations of AMD were determined by high performance liquid chromatography. One hundred and fifty-one trough concentrations from 23 patients receiving repetitive oral AMD were collected. Body mass index (BMI) and body fat percentage were measured.
Results:  Estimates generated using nonmem indicated that the clearance of AMD was influenced by BMI, age and daily dosage of AMD. The final pharmacokinetic model was CL (L/h) = 0·16 · TBW · 0·53^AGE ≥ 65 · 0·78^BMI ≥ 25 · DD^0·51, V _d (L) = 10·2 · TBW, where CL is total body clearance, TBW is total body weight (kg), DD (mg/kg/day) is daily dosage of AMD, AGE (years) ≥65 = 1 for patient was 65 years old or over and 0 otherwise, BMI (kg/m²) ≥25 = 1 for patient was 25 kg/m² or over and 0 otherwise and V _d is apparent volume of distribution. The clearance of AMD decreased significantly by 22·3% with a BMI higher than 25 kg/m². The clearance of AMD also decreased significantly by 46·9% when patient age was more than 65 years.
Conclusion:  Population pharmacokinetic analysis confirms that obesity affects the pharmacokinetics of AMD.     

Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology

Background  Recent data suggest that tryptase, a mast cell enzyme, is expressed in neoplastic cells in myeloid leukaemias. In several of these patients, increased serum tryptase levels are detectable.
Materials and methods  We have determined serum tryptase levels in 914 patients with haematological malignancies, including myeloproliferative disorders ( n  = 156), myelodysplastic syndromes (MDS, n  = 241), acute myeloid leukaemia (AML, n  = 317), systemic mastocytosis (SM, n  = 81), non-Hodgkin's lymphoma ( n  = 59) and acute lymphoblastic leukaemia ( n  = 26). Moreover, tryptase was measured in 136 patients with non-neoplastic haematological disorders, 102 with non-haematological disorders and 164 healthy subjects.
Results  In healthy subjects, the median serum tryptase was 5·2 ng mL⁻¹. Elevated serum tryptase levels were found to cluster in myeloid neoplasm, whereas almost all patients with lymphoid neoplasms exhibited normal tryptase. Among myeloid neoplasms, elevated tryptase levels (> 15 ng mL⁻¹) were recorded in > 90% of patients with SM, 38% with AML, 34% with CML and 25% with MDS. The highest tryptase levels, often > 1000 ng mL⁻¹, were found in advanced SM and core-binding-factor leukaemias. In most patients with non-neoplastic haematological disorders and non-haematological disorders analysed in our study, tryptase levels were normal, the exception being a few patients with end-stage kidney disease and helminth infections, in whom a slightly elevated tryptase was found.
Conclusions  In summary, tryptase is a new diagnostic marker of myeloid neoplasms and a useful test in clinical haematology.     

The hormone sensitive lipase gene in familial combined hyperlipidemia and insulin resistance

Backround Insulin resistance in the most common familial dyslipidemia, familial combined hyperlipidemia (FCHL), could be due to variations in the hormone sensitive lipase (HSL) gene.
Materials and methods The coding region of the HSL gene was screened with the single strand conformation polymorphism analysis in probands of 27 FCHL families with 228 members. In addition, the C-60G promoter substitution of the HSL gene was determined by the restriction fragment length polymorphism analysis in these subjects.
Results No variants in the coding region of the HSL gene were found and the allele frequencies of the C-60G promoter substitution and the silent variant (G3138A) in the 3' untranslated region did not differ between 110 control subjects and 27 probands with FCHL. However, in control women the C-60G substitution was associated with high body mass index [30·6 ± 0·9 kg m⁻² (mean ± SD) in subjects with the C/G genotype and 24·8 ± 4·6 in subjects with the C/C genotype, P  = 0·012], and in control men with high rates of insulin-stimulated whole body glucose uptake (70·1 ± 14·7 vs. 56·7 ± 14·2 µmol kg⁻¹ min⁻¹, P  = 0·014). In 228 FCHL family members this substitution was associated with high low-density lipoprotein cholesterol levels in men (4·51 ± 1·12 vs. 5·17 ± 1·28 mmol L⁻¹, P  = 0·049), but not in women.
Conclusions The HSL gene is not a major gene for FCHL. However, the − 60G allele of this gene may affect body weight, insulin sensitivity and serum cholesterol levels.     

Structural study on immunoglobulin G solution after pasteurization with and without stabilizer

summary .  Pasteurization was investigated as a method of inactivating virus during the preparation of immunoglobulin for intravenous use. The effect of pH, protein concentration and the presence of protein stabilizers on the structure of immunoglobulin G (IgG) molecules during pasteurization was investigated using an immunoglobulin solution derived from a Cohn's fraction II preparation. Changes in the secondary and tertiary structure of IgG molecules as well as the degree of polymerization of protein were investigated using spectrophotometry, circular dichroism and size exclusion chromatography. Only slight changes in secondary and tertiary structure were observed after pasteurization in a 10 g L⁻¹ immunoglobulin solution at pH 4·5 and 5·5 in the absence of stabilizer and in a 50 g L⁻¹ immunoglobulin solution at pH 5·5 in the presence of glycine and sucrose or sorbitol. Concentrations of immunoglobulin solution below 20 g L⁻¹ were not denatured when pasteurized at pH 4·5 in the absence of stabilizers. High concentrations of immunoglobulin solution required stabilizers such as glycine and sorbitol or sucrose to prevent or reduce denaturation during pasteurization.     

CD31+/Annexin V+ microparticles in healthy offsprings of patients with coronary artery disease

Background  First-degree relatives of patients with premature coronary artery disease (CAD) develop endothelial dysfunction even in the case they are apparently healthy. In this study we wanted to clarify whether reduced blood levels of circulating endothelial progenitor cells (EPCs), an endogenous repair mechanism to replace dysfunctional endothelium, or elevated endothelial-derived microparticles (EMPs), an indicator and a mediator of increased endothelial cell damage/apoptosis, are an initial step in the pathogenesis of endothelial dysfunction in genetically predisposed subjects.
Materials and methods  Fifty-six healthy young men (aged 23 to 31 years) from a fire brigade were enrolled, of which 20 subjects had a positive family history (FH) for premature CAD. Subjects with or without a positive FH did not differ with respect to age, body mass index, risk factors and C-reactive protein. Endothelial function was assessed by hyperaemia-mediated relaxation of the brachial artery, blood levels of EPCs (VEGFR2⁺CD34⁺ cells) and number of EMPs (CD31^+(bright)/Annexin V⁺ particles) were analysed by flow cytometry.
Results  Hyperaemia-mediated relaxation of the brachial artery was similar in both groups, and the blood levels of EPCs were comparable. However, the number of EMPs were significantly increased in subjects with a positive FH compared to those with a negative FH (neg. FH: 55·31 ± 4·88 vs. pos. FH: 70·37 ± 6·32 particles µL⁻¹ platelet poor plasma; P  < 0·05). Number of EMPs correlate inversely with the FMD response.
Conclusions  These results suggest that increased plasma levels of EMPs may be an initial step in the development of endothelial dysfunction in genetically predisposed subjects.     

Folate, homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) 677C → T variant, and the risk of myocardial infarction in young women: effect of female hormones on homocysteine levels

Summary.  In young women data are limited about the association between myocardial infarction (MI) and hyperhomocysteinemia, low folate or methylenetetrahydrofolate reductase ( MTHFR ) genotypes. The effect of oral contraceptive (OC) use on plasma homocysteine levels is not clear. We assessed the association between hyperhomocysteinemia, low folate, MTHFR 677TT mutation and risk of MI, and we investigated the effect of OC use on homocysteine levels in controls. In 181 patients with a first MI and 601 controls 18–49 years of age from a population-based case–control study, non-fasting blood samples were available. The homozygote mutant allele (TT) was detected in 12% of the patients and in 10% of controls. The odds ratio (OR) for MI in TT patients compared with the wild-type (CC) controls was 1.3 [95% confidence interval (CI) 0.8, 2.3]. For all MTHFR genotypes combined, the OR for MI in the lowest quartile of folate (<5.4 nmol L⁻¹) compared with the highest quartile (>10.4 nmol L⁻¹) was 3.0 (95% CI 1.7, 5.1). A 2-fold increased risk of MI was found in women with the TT genotype who had folate levels below the median of 7.4 nmol L⁻¹ compared with CC genotype and folate levels above the median (OR = 2.0; 95% CI 1.0, 3.7). Mean homocysteine levels were 12.2 µmol L⁻¹ in OC users and 12.3 µmol L⁻¹ in non-users. Only at the 97.5 percentile (cut-off 21.0 µmol L⁻¹) was the adjusted OR for higher vs. lower homocysteine levels increased by 2.8-fold (95% CI 1.2, 6.8). Low folate is a risk factor for MI, particularly in women with the MTHFR 677TT genotype. Homocysteine levels were not influenced by OC use.     

Mesangial medium with IgA1 from IgA nephropathy inhibits nephrin expression in mouse podocytes

Background  IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA1, and podocyte injury plays an important role in glomerulosclerosis of the disease. Our previous study indicated that medium of mesangial cells co-incubated with aggregated IgA1 (aIgA1), isolated from IgAN patients, down-regulated nephrin expression. Yet the mechanism remains unclear.
Materials and methods  Podocytes were incubated with a medium of mesangial cells co-incubated with aIgA1, which was isolated from IgAN patients, and enalaprilat (10⁻⁵ M), valsartan (10⁻⁵ M) and anti-mouse tumour necrosis factor-α antibody (50 ng mL⁻¹) separately. Nephrin expression in podocytes was measured by real-time polymerase chain reaction and Western blot analysis.
Results  The level of angiotensinogen and angiotensin-converting enzyme mRNAs in podocytes, as well as angiotensin, was also increased by a medium of mesangial cells co-incubated with aIgA1 from IgAN patients( P  <   0·05). Enalaprilat or valsartan partly improved nephrin expression when compared with that by podocytes exposed to the mesangial medium ( P  <   0·05), while the nephrin expression of podocytes with enalaprilat or valsartan was lower than that of podocytes exposed to medium of mesangial cells stimulated by aIgA1 from healthy control ( P  <   0·05). However, anti-mouse tumour necrosis factor-α antibody did not show any improvement in nephrin expression.
Conclusion  Our findings implicate that local renin angiotensin system activation in podocytes is partly involved in down-regulation of nephrin by mesangial medium in IgA nephropathy.     

Cardiac involvement in acute thrombotic thrombocytopenic purpura: association with troponin T and IgG antibodies to ADAMTS 13

Summary.  Introduction: Evidence for cardiac involvement in thrombotic thrombocytopenic purpura (TTP) is uncommonly described. Methodology: We retrospectively reviewed 41 patients assessing troponin T as a marker for cardiac involvement in acute TTP with clinical symptoms, electrocardiograms (ECG) and echocardiograms. A histopathological review of five patients who died of acute TTP was also undertaken. Results: In 54% (22/41) of patients, troponin T was ≥ 0.05μg L⁻¹ (normal range 0–0.01 μg L⁻¹). Half (12/22) had cardiac symptoms and 8/22 with a raised troponin T reported chest pain. ECG changes were present in 62% of patients with a raised troponin T. Median anti-ADAMTS 13 IgG antibody was significantly higher ( P  = 0.018) in patients with troponin T ≥ 0.05 μg L⁻¹ (58.5% (range 17–162%), compared with patients with troponin T < 0.05 μg L⁻¹ (35%, range 9–134%). Patients who died had higher troponin T levels (median 0.305 μg L⁻¹) and raised anti-ADAMTS 13 IgG (median 66.5%). On admission, there were no deaths in those with troponin T ≤ 0.04μg L⁻¹. Histology confirmed widespread myocardial microvascular thrombi. Conclusion: Clinical symptoms, ECG changes and echocardiograms are poor predictors of cardiac disease in acute TTP. Troponin T is specific for cardiac muscle and a sensitive marker of myocardial damage. In TTP patients, raised levels (≥ 0.05 μg L⁻¹) signify myocardial necrosis associated with microvascular thrombi. Mortality and acute morbidity was associated with higher admission troponin T and raised IgG antibody (> 67%) to ADAMTS 13.     

P38An Acute Hemolytic Transfusion Reaction Due to Anti-Wra Antibodies.

The Wr^a antigen is found on the red blood cells of approximately 1 : 1000 caucasians. Anti-Wr^a antibodies have been reported to be present in 1 : 25 to 1 : 100 healthy blood donors and an even higher proportion of hospital patients. Wr^a incompatibilty might therefore be expected to occur in approximately one in 50,000 blood transfusions. Reports of hemolytic transfusion reactions (HTR) and hemolytic disease of the newborn (HDN) due to anti-Wr^a are however rare. We report an acute HTR due to anti- Wr^a in a 58 year old male with MDS associated with rigors, shortness of breath and a significant rise in serum bilirubin from 16 μmol L⁻¹ pre-transfusion to 110 μmol L⁻¹ immediately afterwards. This was accompanied by the appearance of bilirubin and urobilinogen in his urine and a fall in haemoglobin of nearly 2 g dL⁻¹ following the transfusion. Anti- Wr^a was the only antibody implicated. Wr^a antigen expressing reference panel cells and the unit being transfused during the gave 2–3+ reactions by IAT against the recipient's plasma. The donation typed as positive with Wr^a antisera. The recipient typed as Wr^a antigen negative. The reaction resulted in the patient being admitted to hospital for 2 days. The increasing use of electronic issue may result in more frequent reports of reactions due to anti-Wr^a as commonly used screening cells do not express this antigen.     

Coagulation factor XII (FXII) activity, activated FXII, distribution of FXII C46T gene polymorphism and coronary risk

Summary.  Background:  Whether factor XII (FXII) activity, its 46C>T polymorphism and activated FXII (FXIIa) are associated with coronary heart disease (CHD) remains to be determined. Methods:  FXII, FXIIa and the FXII 46C>T polymorphism were determined in a hospital-based cohort of 2615 patients undergoing coronary angiography. Results:  Fifty-seven per cent of the participants were identified as wild-type (46CC), 38% as heterozygous (46CT) and 5% as homozygous (46TT) for FXII 46C>T. FXII and FXIIa levels were significantly lower in carriers of the T-allele: 132 (97–151) U dL⁻¹ FXII in 46CC, 87 (77–99) U dL⁻¹ FXII in 46CT and 53 (42–67) U dL⁻¹ FXII in 46TT carriers ( P  <   0.001), and 2.8 (2.3–3.5) μg L⁻¹ FXIIa in CC, 2.1 (1.6–2.6) μg L⁻¹ FXIIa in CT and 1.2 (0.9–1.5) μg L⁻¹ FXIIa in TT carriers ( P  <   0.001; medians, lower and upper quartiles). Patients with stable CHD ( n  =   935), a history of myocardial infarction ( n  =   785) or who were suffering from acute coronary syndromes (ACS; n  =   323) had significantly lower FXII levels than controls ( n  =   572). The differences remained statistically significant after adjustments for age, sex, diabetes mellitus, smoking, hypercholesterolemia and hypertension. Significantly reduced FXIIa levels in ACS patients lost significance once adjusted for covariates. FXII genotype was not associated with any clinical phenotype. Conclusion:  Lower FXII activity represents an independent risk for CHD and ACS. This is not the case for FXIIa levels or the FXII 46C>T variation.     

The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide (GIP) in man

Abstract. The pharmacokinetics of porcine glucose-dependent insulinotropic polypeptide were investigated in six healthy volunteers. At the maximum infusion dose (0·5 pmol kg^-1 min^-1) a plateau concentration of 115 ± 5·0 pmol/l plasma was obtained. On discontinuation of the infusion, the half-time of disappearance was calculated to be 20·3 ± 1·2 min. The metabolic clearance rate was 2·6 ± 0·1 ml kg^-1 min^-1 and the apparent space of distribution was 75·8 ± 5·7 ml kg^-1. Blood glucose, pancreatic and gastrointestinal hormones remained at basal concentrations throughout. No side effects were noted by any of the subjects studied.     

Tumour-specific induction of immune complexes: DCP-IgM in hepatocellular carcinoma

Background   In the sera of liver, colorectal and prostate cancer patients, several biomarkers may be detected as IgM immune complexes. To determine whether the presence of immune complexes was correlated to an increase of IgMs, we measured the IgM content in the sera of patients with hepatocellular carcinoma (HCC) and cirrhosis, and evaluated the occurrence of des-gamma-carboxy prothrombin (DCP) as immune complexes ( DCP-IgM ) compared to the levels of DCP and alpha-fetoprotein (AFP).
Patients and methods   Serum samples from 31 patients with cirrhosis, 33 untreated HCC patients diagnosed by ultrasound, computed tomography and/or magnetic resonance and confirmed by histopathology, when indicated, and 30 healthy controls were analysed. Concentrations of IgM and DCP-IgM were determined by ELISAs.
Results   Circulating IgM in patients with HCC (median level = 1·79 mg mL⁻¹) and cirrhosis (1·09 mg mL⁻¹) were not significantly different ( P  = 0·1376) while DCP-IgM were significantly higher in HCC patients (median level = 2171·2 AU mL⁻¹) than in those with cirrhosis (1152 AU mL⁻¹, P  = 0·0047). No correlation was found between DCP-IgM and IgM in HCC ( r  = 0·227) and cirrhosis patients ( r  = 0·475). DPC-IgM was positive in 55% (18/33) of HCC patients and in 26% (8/31) of cirrhosis patients compared to 39% and 26% for DCP and 48% and 13% for AFP. DCP-IgM, DCP and AFP tests had 100% specificity in healthy controls.
Conclusions   DCP-IgM in HCC patients was not associated with an increase in IgM concentration. DCP-IgM was more frequently detected in HCC patients than DCP and AFP, strengthening the diagnostic role of IgM immune complexes for liver cancer.     

The presence of antiphospholipid antibodies is not related to increased levels of annexin A5 in plasma

Summary.  Annexin A5 has been proposed to be important for shielding of negatively charged phospholipids from blood, thereby preventing the binding of clotting factors. It has been suggested that antiphospholipid antibodies can disrupt the binding of annexin A5 from negatively phospholipid-containing surfaces, resulting in uncontrolled coagulation. If this hypothesis is correct, than the plasma levels of annexin A5 will be increased in patients with antiphospholipid antibodies. Therefore, we have measured plasma levels of annexin A5 of 175 patients with systemic lupus erythematosus (SLE), of which 104 had antiphospholipid antibodies and 23 patients had primary antiphospholipid syndrome. The annexin A5 levels were compared with the annexin A5 plasma levels measured in 23 patients with diabetes mellitus type 2 and 35 healthy volunteers. We found a significant increase of annexin A5 plasma levels in patients with SLE (median 6.7 ng mL⁻¹) and primary antiphospholipid syndrome (median 7.1 ng mL⁻¹) as compared to patients with diabetes mellitus type 2 (median 3.3 ng mL⁻¹) and healthy volunteers (median 3.9 ng mL⁻¹). However, no correlation was found with the presence of antiphospholipid antibodies or with a history of thromboembolic complications. Based on these observations, we conclude that displacement of annexin A5 from cellular surfaces by antiphospholipid antibodies is not a common mechanism in patients with antiphospholipid antibodies.     

The use of D-dimer testing and Wells score in patients with high probability for acute pulmonary embolism

Rationale, aims and objective  To investigate if a combination of Wells pre-test probability score and D-dimer testing could be used as a safe base for making clinical decisions on further investigations for patients with intermediate to high risks of pulmonary embolism (PE).
Methods  One hundred and twenty patients with signs or symptoms of acute PE were investigated with pulmonary angiography (PA) or contrast enhanced computed tomography of the pulmonary arteries (CTPA), D-dimer testing (Tinaquant^®) and clinical scoring using the Wells pre-test probability score during their first 48 hours at the hospital. Patients were recruited consecutively from emergency departments at two teaching hospitals.
Results  The cut-off value of 0.5 mg L⁻¹ in D-dimer analysis is proved adequate with a negative predictive value (NPV) of 92% in this group of patients with intermediate to high risks. The combination of D-dimer testing and Wells score increases the NPV to 94%. The specificities of both tests were low.
Conclusion  D-dimer and Wells pre-test probability scores are safe to rule out acute PE even in patients with at least an intermediate risk of PE, but the specificity is low. D-dimer testing had a higher NPV than Wells score and the combination improved the algorithm further. The cut-off level for a high risk of PE measured with the Wells score was four and it seems reasonable to use that cut-off level in future algorithms. In addition, both PA and CTPA can present false positive and negative results difficult to interpret.     

Protoporphyrinogen oxidase and porphobilinogen deaminase in variegate porphyria

Abstract. Two enzymes of the haem biosynthetic pathway were investigated in patients with variegate porphyria. Protoporphyrinogen oxidase in cultures of Epstein-Barr virus transformed lymphoblasts from twenty-seven patients showed a mean maximal velocity ( V _max) of 0·39 ± 0·08⁺ nmol of protoporphyrin mg protein^-1 h^-1, a 52% reduction ( P < 0·001) from a non-porphyric control group (0·82 ± 0·10). K _m values (1·00 ± 0·27 μ M) did not differ significantly ( P > 0·05) from control values in any of the patients. The mean V _max of porphobilinogen deaminase in the cultures was 1·50 ± 0·18 nmol of uroporphyrin mg protein^-1 min^-1, a 24% reduction ( P < 0·001) from controls (1·94 ± 0·14). Mean porphobilinogen deaminase activity in the erythrocytes of twenty-one patients with variegate porphyria was 8·37 ± 1·99 nmol of uroporphyrin 1 erythrocytes^-1 s^-1, a 28% reduction ( P < 0·001) from normal (11·98 ± 2·11). The reduced activities of these two enzymes comply with the expression of variegate porphyria during its quiescent and acute phases.     

Venous compliance and the venodilatory effect of nitroglycerin in insulin-dependent diabetic patients with and without (incipient) nephropathy

Abstract. The venous system plays a pivotal role in volume and blood pressure homeostasis. We tested the hypothesis that the visco-elastic properties of the peripheral venous system are reduced in patients with (incipient) diabetic nephropathy. Twenty-two normotensive patients with long-term insulin-dependent diabetes mellitus (IDDM), 11 without and 11 with (incipient) nephropathy (eight microalbuminuria and three proteinuria, serum creatinine below 100 μmol l^-1), and 14 healthy age/sex matched controls were studied. Forearm venous compliance (VENCOMP) was determined using strain gauge plethysmography and direct intravenous pressure measurements. Furthermore, the venodilatory effect of 0·4 mg sublingual nitroglycerin (NTG) was studied. In comparison with healthy controls, VENCOMP was decreased in patients without and with (incipient) nephropathy, without any differences between the two diabetic groups: 0·059 (0·052–0·066), 0·044 (0·038–0·059) and 0·049 (0·046–0·058) ml 100 ml^-1 mmHg^-1, respectively (medians and interquartile ranges) ( P <0·05). No differences in the increase of forearm volume after NTG were observed: 0·34 (0·11–0·51), 0·37 (0·19–0·50) and 0·39 (0·20–0·55) ml 100 ml^-1, respectively. In conclusion, the visco-elastic properties of the peripheral venous system are reduced in patients with long-term IDDM. This reduction is not related to the presence of nephropathy. No major differences were observed in NTG-induced venodilation between diabetic patients and healthy subjects.