Subjects with a shortened activated partial thromboplastin time show increased in-hospital mortality associated with elevated D-dimer, C-reactive protein and glucose levels.

BACKGROUND: Shortened activated partial thromboplastin time (aPTT) values are associated with enhanced coagulation activation. However, the clinical relevance of shortened aPTTs is not well defined. The aim of this study was to determine the in-hospital mortality rate in subjects with shortened aPTTs and the effects of polymorphism in plasminogen activator inhibitor (PAI)-, t-PA- and factor XIII gene on the coagulation status. D-dimer, C-reactive protein (CRP) and glucose, markers that have been related with increased mortality, were tested. RESULTS: We found that a shortened aPTT on admission was associated with an increased risk of in-hospital mortality (OR=2.6, 95% CI: 2.1-3.5). Non-survivors with short aPTTs had significantly higher plasma D-dimer, CRP and glucose levels compared with survivors. Subjects homozygous for PAI-1 5G and t-PA I alleles showed higher plasma D-dimer levels compared with 4G/4G PAI-1 (p=0.02) and D/D t-PA (p=0.001) homozygotes, respectively. CONCLUSIONS: These results suggest that PAI-1 4G/5G and t-PA I/D polymorphisms determine plasma D-dimer levels in patients with shortened aPTT values. Preliminary results show that, among patients with short aPTTs, homozygosity for the hyperfibrinolytic PAI-1 5G or tPA I alleles are at increased risk of in-hospital mortality compared with 4G/4G PAI-1 and D/D tPA homozygotes (OR=2.6, 95% CI: 1.3-5.5 and OR=5.5, 95% CI: 1.3-24.5, respectively).

Iron deficiency anaemia in hospitalised patients: value of various laboratory parameters. Differentiation between IDA and ACD.

BACKGROUND: for the diagnostic evaluation of microcytic or normocytic anaemia in a heterogeneous group of patients, the value of newer parameters, such as zinc protoporphyrin (ZPP), plasma transferrin receptor (PtrfR) and PtrfR/ferritin ratio is not clear. We have performed a prospective study to determine the predictive value of these parameters and ferritin, for diagnosing iron deficiency anaemia (IDA). METHODS: sixty-two patients with Hb<8.2 (men) or <7.0 (women) and mean cell volume (MCV)<96 fl were included. Exclusion criteria were: known haematological disease, pregnancy, bone marrow suppression or iron therapy within the previous 7 days. Bone marrow examination was used as a golden standard to discriminate between IDA and non-IDA. RESULTS: twenty-four patients had depleted iron stores. We found that the reticulocyte response on iron supplementation correlated well with the iron-status of the bone marrow. Univariate analysis showed that ferritin, PtrfR/ferritin ratio, ZPP and PtrfR have significant predictive values for differentiating IDA from non-IDA. Interestingly, multivariate analysis revealed that ferritin was the only significant, independent predictor of IDA, with a cut-off point of 32 microg/l (sensitivity 79.2%, specificity 96.9%). CONCLUSIONS: the low sensitivity and specificity of ZPP, PtrfR and PtrfR/ferritin ratio render them insufficient to be used as a single 'best' test for the identification IDA in a non-selected group of anaemic patients and do not even add to the prediction if the value of ferritin is known.

Diagnosing alcoholism in high-risk drinking drivers: comparing different diagnostic procedures with estimated prevalence of hazardous alcohol use.

In several European countries, drivers under influence (DUI), suspected of an alcohol use disorder (AUD, 'alcoholism') are referred for diagnostic examination. The accuracy of diagnostic procedures used in diagnosing AUD in the DUI population is unknown. The aim of this study was to compare three prevalence estimates of AUD based on a structured clinical interview (SCID), a restrictive diagnostic procedure (RDP) and usual clinical diagnostic procedure (CDP), with a prevalence estimate based on sensitivity and specificity data of biological markers of excessive use of alcohol in non-judicial samples. The latter unbiased estimate provides an external yardstick against which the biased patient-based prevalence estimates in this special sample can be evaluated. The unbiased estimate derived from sensitivity and specificity data resulted in a prevalence estimate of excessive use of alcohol between 74 and 82%, which is much higher than the three diagnostic procedures. SCID identified maximally 5% of alcoholics found with the unbiased estimate. RDP identified > or =31% of the unbiased estimate, while CDP identified > or =60% of the unbiased estimate. The high chance of false positive diagnosis, however, makes CDP unacceptable in the legal context of AUD diagnosis in DUI populations.

Developing a population-based registry for patients with paraproteinemias or multiple myeloma.

The development of a population-based registry on paraproteinemia and multiple myeloma is described. A unique feature of this registry is the multidisciplinary approach to obtain and collect new cases. Clinical chemists, internists, hematologists, and pathologists could all enter patients. All patients newly diagnosed in the mid-western part of The Netherlands (1.7 million inhabitants in 1992) with a paraproteinemia or multiple myeloma in 1991, 1992, and 1993 were included. The project was composed of a registry of clinical and laboratory data extracted from the patient's records, storage of 1 ml serum at diagnosis, and a yearly follow-up. A total of 1832 entries was received, of which 83% met the inclusion criteria. Comparison of this database with the Regional Cancer Registry showed that the paraprotein registry was successful as far as registration of myeloma patients was concerned. We conclude that the multidisciplinary approach used in this paraprotein registry is feasible and has resulted in a unique collection of patients for studying potential pre-malignant conditions such as paraproteinemia.

Development of a "Myeloma Risk Score" using a population-based registry on paraproteinemia and myeloma.

Diagnostic systems for monoclonal gammopathies use bone marrow and X-ray examinations to exclude multiple myeloma (MM). Data from a population-based registry of unselected patients with paraproteinemia indicate that these tests are often done only when MM is suspected. We used 441 randomly selected patients to develop a simple four point "Myeloma Risk Score" based on two readily available laboratory tests. One point was given for paraprotein concentration > or = 10 g/l, one point for IgG and IgA, and two points for IgD and light chains only. A score of 0 or 1 indicated a low risk for MM, with scores of 2 and 3 signifying high risks. Sensitivity, specificity, positive and negative predictive value (PV) for the Myeloma Risk Score in the training sample were 92%, 88%, 79%, and 96% respectively. Extrapolating these results to a larger cohort showed that 90% of patients with a monoclonal gammopathy could be classified correctly as having MM or a non-myeloma condition. The Myeloma Risk Score can identify patients with a paraproteinemia at risk for MM, and who are therefore candidates for bone marrow and X-ray examination.

A population-based registry on paraproteinaemia in The Netherlands. Comprehensive Cancer Centre West, Leiden, The Netherlands.

Patients with monoclonal gammopathies comprise a heterogenous group. The few studies on incidence and follow-up are single-centre-based and may reflect referral bias. To avoid this, all patients (n=1275) in midwestern Netherlands with a newly discovered paraproteinaemia in 1991, 1992 and 1993 were included in a population-based registry and divided into four major diagnostic groups: multiple myeloma and plasmacytoma (n=230, 18%), other haematological diseases (n=141, 11%), paraprotein-related internal diseases (n=191, 15%) and monoclonal gammopathy of undetermined significance (MGUS, n=713, 56%). To avoid a possibly erroneous diagnosis, patients who were classified as having MGUS but who did not undergo confirmatory bone marrow examination were included in a separate group 'provisional MGUS' (n=524, 41%), whereas patients who did were classified as having 'definite MGUS' (n=189, 15%). The 'provisional MGUS' patients were relatively older and had more often a poor performance status, but differences between this and the 'definite MGUS' group were otherwise small. Patients complaining of general malaise more often had a full work-up of their paraproteinaemia. Bone pain, hypercalcaemia, high total protein, and high ESR occurred predominantly in the myeloma group, whereas fever or infection was less often seen in these patients. This registry of patients with paraproteinaemias provided valuable data related to all different diseases associated with paraproteinaemia.

Serum neural cell adhesion molecule differentiates multiple myeloma from paraproteinemias due to other causes.

Serum neural cell adhesion molecule (NCAM) has been described as a prognostic marker in multiple myeloma (MM). Both C-reactive protein (CRP) and beta 2-microglobulin (beta 2M) are established prognostic markers in MM. We tested the diagnostic value of these markers in 212 serum samples of patients with paraproteinemia registered prospectively in a population-based registry. Sixty patients had MM and 152 had other monoclonal gammopathies (hematologic diseases [48], paraneoplastic disease [35], autoimmune disease [15], and monoclonal gammopathy of undetermined significance [56]). CRP and beta 2M had wide and overlapping ranges in all diagnostic categories. However, serum neural cell adhesion molecule (NCAM) was low (< 20 U/mL) in all but 4 of 152 nonmyeloma cases and high (> or = 20 U/mL) in 31 (52%) of the 60 MM cases. Two patients with non-Hodgkin's lymphoma, 1 with chronic lymphatic leukemia, and 1 with autoimmune disease had serum NCAM values between 20 and 30 U/mL. In a discriminant analysis in which serum NCAM, CRP, beta 2M, paraprotein type and concentration, hemoglobin, leukocyte and thrombocyte counts, creatinine, corrected calcium, lactate dehydrogenase, and alkaline phosphatase were included, paraprotein type and concentration and serum NCAM turned out to be the best combination of parameters predicting whether a patient had MM, with 89% of cases being correctly classified. Even without bone marrow and x-ray examinations, serum NCAM, in combination with paraprotein type and concentration, can differentiate between MM and nonmyeloma patients.

The effect of orgasm on prostate-specific antigen.

To identify the effect of orgasm on serum prostate-specific antigen (PSA) levels, a prospective trial before and after orgasm was performed in 14 healthy colleagues aged 32-62 years (mean, 44.4 years) with no evidence of prostatic disease. PSA determinations were performed on serum samples obtained before and after orgasm. Significant changes in PSA levels after orgasm were found (P = 0.002, analysis of variance). We conclude that the impact of orgasm on PSA levels should be taken into account when the latter are used for the detection of prostatic disease.

Recognition and prevention of two cases of erroneous haemocytometry counts due to platelet and white blood cell aggregation. The use of acid citrate dextrose as an auxiliary anticoagulant.

Two cases of anticoagulant-induced platelet-white blood cell aggregation are described, which resulted in erroneous haemocytometry counts. Aggregation was avoided by the use of acid citrate dextrose (ACD) as an auxiliary anticoagulant, thus enabling quantification of platelets and white blood cells.

Recognition and prevention of pseudothrombocytopenia and concomitant pseudoleukocytosis.

Unrecognized anticoagulant-induced platelet (PLT) aggregation, leading to pseudothrombocytopenia and concomitant pseudoleukocytosis, can have serious clinical consequences. It can be readily recognized by inspecting conventional blood smears or the white blood cell histograms generated by modern blood cell counters. Blood specimens from twenty patients with known EDTA-induced platelet aggregation were consecutively drawn into three other anticoagulants (using Vacutainer tubes) and processed in a three-part differential Coulter Counter S Plus IV. PLT aggregation is shown to be generally induced by Li-heparin but much less frequently by citrate solutions. Prevention is almost invariably achieved by acid citrate dextrose (ACD). To that end approximately 2.5 mL of sterile ACD was aseptically injected beforehand through the stoppers of plain 5 mL Vacutainer tubes without breaking the vacuum. After blood drawing, correction for dilution was made by comparing hemoglobin values in EDTA and ACD.

Pediatric reference values for calcium, magnesium and inorganic phosphorus in serum obtained from Bhattacharya plots for data from unselected patients.

Pediatric reference values for total calcium, magnesium and inorganic phosphorus are given. The values were determined by using Bhattacharya plots for unselected data. The reference values for calcium (from 8320 values from patients) and magnesium (from 1231 values from patients) show only minor dependence on age. Reference values for ages up to 20 years for calcium were 2.14-2.64 mmol/l and for magnesium 0.57-1.12 mmol/l. However, for inorganic phosphorus (3349 values from patients) a gradual decrease in concentration occurred throughout childhood from 1.56-2.29 mmol/l (less than 1 year) to 1.03-1.78 mmol/l (greater than 15 years).

Technetium radiopharmaceuticals: chemical characterization and tissue distribution of Tc-glucoheptonate using Tc-99m and carrier Tc-99.

The chemical structure of the kidney- and brain-imaging agent Tc-99m glucoheptonate has been established using the Tc-99 isotope. In a comparative study between Tc-99 and Tc-99m glucoheptonates, chromatographic, electrophoretic, and tissue distribution studies showed identical compounds in 0.9% NaCl. Optimal conditions for the formation of the Tc-99 glucoheptonate complex were investigated by uv and visible spectroscopy. The oxidation state of Tc-99 in the compound is V, measured by Sn2+ titration. The complex contains a Tc = O core and two glucoheptonate ligands (oxobis(glucoheptonato)technetate(V) anion (net charge: -1) in aqueous solution). NMR studies demonstrated two five-membered glucoheptonate rings, bidentate bound to Tc by the oxygens of the end carboxyl group and the adjacent hydroxyl group. The compound is stabilized by interaction between Tc-99 and one of the hydroxyloxygens of glucoheptonate at the vacant coordination site trans to the Tc = O core. Experiments with the reducing agent NaBH4 demonstrated the absence of Sn (II or IV) in the complex and a biological behavior independent of the reducing agent used.