Biotests and biosensors in ecotoxicological risk assessment of field soils polluted with zinc, lead, and cadmium

The combined chemical and ecotoxicological hazard evaluation study was conducted on 60 smelter-influenced soils containing 1 to 13, 50 to 653, and 100 to 1,198 mg/kg of Cd, Pb, and Zn, respectively. For these soils (liquid-to-soil ratio = 10), water extractability of Zn, Cd, and Pb was less than 0.19% (median values). Acetic acid (0.11 M) extracted 23, 9.7, and 0.7% of Cd, Zn, and Pb, respectively. Although heavy metal concentrations in the studied soils were high, the toxic effects of water extracts were observed only in few samples and in few biotests (algae Selenastrum capricornutum and metal detector assay). For most of the aquatic test organisms (e.g., crustaceans, photobacteria), the bioavailable concentrations of metals in soil-water extracts were either subtoxic, or the adverse effects were compensated by soil nutrients, etc. However, analysis of the soils with recombinant Cd sensor Bacillus subtilis (pTOO24) showed that about 65% of these apparently subtoxic samples contained bioavailable Cd when analyzed in the suspension assay (detection limit 1.5 mg Cd/kg soil), indicating the desorption of Cd induced by direct contact of bacteria with soil particles. The median bioavailable fraction of Cd (1%) was 23-fold lower than the fraction extracted by acetic acid. The Pb-Cd sensor Staphylococcus aureus (pT0024) detected bioavailable Pb only in the suspensions of five of the most lead-polluted soils (>417 mg Pb/kg): the median bioavailability of Pb was 0.42%. Consequently, the hazard assessment relying on total metal levels in soils should be revised by critical comparison with data obtained from bioassays. Development and use of biosensors (excellent tools for mechanistic studies and signaling hazard already at subtoxic level) should be encouraged.     

Verwijdering van pyrogenen uit parenterale toedieningsvormen

Samenvatting Ter verwijdering van pyrogenen uit kleine hoeveelheden vloeistof bedoeld voor parenterale toediening (injecties, incidentele infusen) is gekeken naar vervanging van het losse asbest. Besproken wordt de apparatuur voor adsorptiefiltratie en ultrafiltratie; ultrafiltratie verdient ons inziens de voorkeur.

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Naar een bijvakonderzoek aan de subfaculteit Farmacie, Rijksuniversiteit Utrecht.     

Risk factors for fetal-to-maternal transfusion in Rh D-negative women--results of a prospective study on 942 pregnant women

AIMS: To investigate the incidence of severe fetal-to-maternal transfusion after delivery and to identify risk factors. MATERIAL AND METHODS: In a prospective study at the Department of Obstetrics, Charité, Campus Virchow-Klinikum, Berlin, Germany, we analyzed the incidence of severe fetal-to-maternal transfusion (>10 ml) and fetal-to-maternal hemorrhage (>25 ml) in Rh D-negative pregnant women after delivery of Rh D-positive infants. 942 women were included in the study and Kleihauer-Betke tests were performed. The results were compared to perinatal data. RESULTS: Fetal-to-maternal hemorrhage occurred in 13 cases out of 942 (incidence of 1.3%) and severe fetal-to-maternal transfusion in 61 cases (6.5%). In all of the cases with fetal-to-maternal hemorrhage, mothers were compatible with their infants in ABO-system. The incidence of fetal-to-maternal transfusion and its severe form was significantly higher in twin pregnancies (7/21 cases and 5/21 cases respectively, 33.3% and 23.8%) than in singleton pregnancies (22.5%, and 5.9%, P<0.001). All other factors, such as maternal age, parity, ethnicity, mode of delivery, presentation, duration of first and second stage of labor, CTG, or Apgar score were not associated with an increased risk of severe fetal-to-maternal transfusion. CONCLUSIONS: Twin pregnancy is the only independent risk factor for severe fetal-to-maternal transfusion. ABO-incompatibility between mother and infant seems to be protective against Rh D-alloimmunization.     

Objective measurement of hyperactivity, impulsivity, and inattention in children with hyperkinetic disorders before and after treatment with methylphenidate

PURPOSE: The purpose of this study was to investigate whether values of the respective parameters of the OPTAx test dependently differ due to the medication with methylphenidate (MPH) in children with hyperkinetic disorders (HD) suffering from hyperactivity, impulsivity, and attention deficits. METHODS: The OPTAx test is an infrared motion analysis to record the movement pattern during a continuous performance test. We tested 25 children between 6 and 12 years with HD (ICD-10: F90.0 or F90.1) before and after treatment with MPH. The parameters under investigation were activity (microevents and spatial scaling), impulsivity (errors of commission), and attentiveness (accuracy and variability). For statistical analysis a one-tailed matched pairs test (adj. p = 0.01) was conducted to discriminate differences found from those occurred at random. A post hoc partial correlation of absolute differences in the respective parameters and the daily dose of MPH (adj. for BMI) was performed if p < 0.01. RESULTS: Statistically significant results were found for microevents, spatial scaling, errors of commission, accuracy, and variability. The partial correlation showed significant results for microevents and variability. CONCLUSION: The mean pre-post changes found in all parameters investigated consistently correspond with benefits desired from medication with MPH in children with HD. Absolute differences in microevents and variability seem to depend on the daily dose of MPH after adjustment for BMI.     

Cost effectiveness of interventions for lateral epicondylitis: results from a randomised controlled trial in primary care

OBJECTIVE: Lateral epicondylitis is a common complaint, with an annual incidence between 1% and 3% in the general population. The Dutch College of General Practitioners in The Netherlands has issued guidelines that recommend a wait-and-see policy. However, these guidelines are not evidence based. DESIGN AND SETTING: This paper presents the results of an economic evaluation in conjunction with a randomised controlled trial to evaluate the effects of three interventions in primary care for patients with lateral epicondylitis. PATIENTS AND INTERVENTIONS: Patients with pain at the lateral side of the elbow were randomised to one of three interventions: a wait-and-see policy, corticosteroid injections or physiotherapy. MAIN OUTCOME MEASURES AND RESULTS: Clinical outcomes included general improvement, pain during the day, elbow disability and QOL. The economic evaluation was conducted from a societal perspective. Direct and indirect costs (in 1999 values) were measured by means of cost diaries over a period of 12 months. Differences in mean costs between groups were evaluated by applying non-parametric bootstrap techniques. The mean total costs per patient for corticosteroid injections were euro430, compared with euro631 for the wait-and-see policy and euro921 for physiotherapy. After 12 months, the success rate in the physiotherapy group (91%) was significantly higher than in the injection group (69%), but only slightly higher than in the wait-and-see group (83%). The differences in costs and effects showed no dominance for any of the three groups. The incremental cost-utility ratios were (approximately): euro7000 per utility gain for the wait-and-see policy versus corticosteroid injections; euro12000 per utility gain for physiotherapy versus corticosteroid injections, and euro34500 for physiotherapy versus the wait-and-see policy. CONCLUSIONS: The results of this economic evaluation provided no reason to update or amend the Dutch guidelines for GPs, which recommend a wait-and-see policy for patients with lateral epicondylitis.     

Progression of diabetic nephropathy

BACKGROUND: Diabetic nephropathy is a major cause of renal failure. The decline in glomerular filtration rate (GFR) is highly variable, ranging from 2 to 20, with a median of 12 mL/min/year. The risk factors of losing filtration power (progression promoters) have not been clearly identified. Furthermore, information on optimal arterial blood pressure, glycemic control, and cholesterol levels are lacking. METHODS: We measured GFR with (51)Cr-EDTA plasma clearance technique, blood pressure, albuminuria, glycosylated hemoglobin A1c, and serum cholesterol every year for seven years (range 3 to 14 years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy recruited consecutively during 1983 through 1997. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria> 200 microg/min, presence of diabetic retinopathy, and no evidence of other kidney or renal tract disease. In total, 271 patients received antihypertensive treatment at the end of the observation period. RESULTS: Mean arterial blood pressure was 102 +/- 0.4 (SE) mm Hg. The average decline in GFR was 4.0 +/- 0.2 mL/min/year and even lower (1.9 +/- 0.5 mL/min/year) in the 30 persistently normotensive patients, none of whom had ever received antihypertensive treatment (P < 0.01). A multiple linear regression analysis revealed a significant positive correlation between the decline in GFR and mean arterial blood pressure, albuminuria, glycosylated hemoglobin A(1c), and serum cholesterol during follow-up (R(adj)(2) = 0.29, P < or = 0.001). No threshold level for blood pressure, glycosylated hemoglobin A(1c), or serum cholesterol was demonstrated. A two-hit model with mean arterial blood pressure and glycosylated hemoglobin A(1c) below and above the median values (102 mm Hg and 9.2%, respectively) revealed a rate of decline in GFR of only 1.5 mL/min/year in the lowest stratum compared with 6.1 mL/min/year in the highest stratum (P < 0.001). CONCLUSIONS: The prognosis of diabetic nephropathy has improved during the past decades, predominantly because of effective antihypertensive treatment. Genuine normotensive patients have a slow progression of nephropathy. Several modifiable variables have been identified as progression promoters.     

Conservative treatments for tennis elbow do subgroups of patients respond differently?

OBJECTIVES: To determine if subgroups of patients with tennis elbow respond differently in treatment. METHODS: This study used individual patient data (n = 383) from two randomized controlled trials that investigated a wait-and-see policy, corticosteroid injections and physiotherapy. Common outcome measures were: pain severity, global improvement, severity assessed by a blinded assessor, elbow disability and pain free grip strength. Subgroup analyses for previous history of elbow pain, baseline pain severity, duration of the current episode and employment status were performed at 6 and 52 weeks. RESULTS: Patients' age, previous elbow symptoms and baseline pain severity were similar between trials, but other characteristics differed between trial populations. Based on individual patient data from both trials, we found that corticosteroid injections were statistically and clinically superior at 6 weeks, but significantly worse at 52 weeks compared with both wait-and-see and physiotherapy. Subgroup effects were scarce and small. Patients with higher baseline pain score showed less benefit on pain outcomes between physiotherapy and a wait-and-see policy at 6 weeks. It also appeared that non-manual workers who had an injection were the only work subgroup to follow the general trend that injections were significantly worse than a wait-and-see policy on global improvement at 52 weeks. CONCLUSION: The treatment outcomes were largely similar between trials and not different between most subgroups studied. In tennis elbow, it would appear that patient characteristics play only a small role in predicting treatment outcomes, which supports the generalizability of individual trial results.     

Reduced transcapillary escape of albumin during acute blood pressure-lowering in Type 1 (insulin-dependent) diabetic patients with nephropathy

Summary The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected ¹²⁵I-labelled human serum albumin), and urinary albumin excretion rate (radial immuno-diffusion). The study was performed twice within 2 weeks, with the patients receiving an intravenous injection of either clonidine (225 g) or saline (0.154 mmol/l). The clonidine injection induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p<0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p<0.01), albuminuria diminished from 1434 to 815 g/min (p<0.01), and plasma volume raised slightly from 2916 to 2995ml (p<0.05). Our findings demonstrate that the enhanced albumin passage through the wall of the microvasculature characteristically found in long-term Type 1 diabetic patients with clinical microangiopathy is pressure-dependent to a large extent. This may be due to elevated hydrostatic pressure in the microcirculation.