Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes.

BACKGROUND AND PURPOSE: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. METHODS: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. RESULTS: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. CONCLUSIONS: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.

Dynamic contrast-enhanced CT in suspected lung cancer: quantitative results.

OBJECTIVES: To examine whether dynamic contrast-enhanced CT (DCE-CT) could be used to characterise and safely distinguish between malignant and benign lung tumours in patients with suspected lung cancer. METHODS: Using a quantitative approach to DCE-CT, two separate sets of regions of interest (ROIs) in tissues were placed in each tumour: large ROIs over the entire tumour and small ROIs over the maximally perfused parts of the tumour. Using mathematical modelling techniques and dedicated perfusion software, this yielded a plethora of results. RESULTS: First, because of their non-normal distribution, DCE-CT measurements must be analysed using log scale data transformation. Second, there were highly significant differences between large ROI and small ROI measurements (p<0.001). Thus, the ROI method used in a given study should always be specified in advance. Third, neither quantitative parameters (blood flow and blood volume) nor semi-quantitative parameters (peak enhancement) could be used to distinguish between malignant and benign tumours. This was irrespective of the method of quantification used for large ROIs (0.13

Superior accuracy of model-based radiostereometric analysis for measurement of polyethylene wear: A phantom study.

OBJECTIVES: The accuracy and precision of two new methods of model-based radiostereometric analysis (RSA) were hypothesised to be superior to a plain radiograph method in the assessment of polyethylene (PE) wear. METHODS: A phantom device was constructed to simulate three-dimensional (3D) PE wear. Images were obtained consecutively for each simulated wear position for each modality. Three commercially available packages were evaluated: model-based RSA using laser-scanned cup models (MB-RSA), model-based RSA using computer-generated elementary geometrical shape models (EGS-RSA), and PolyWare. Precision (95% repeatability limits) and accuracy (Root Mean Square Errors) for two-dimensional (2D) and 3D wear measurements were assessed. RESULTS: The precision for 2D wear measures was 0.078 mm, 0.102 mm, and 0.076 mm for EGS-RSA, MB-RSA, and PolyWare, respectively. For the 3D wear measures the precision was 0.185 mm, 0.189 mm, and 0.244 mm for EGS-RSA, MB-RSA, and PolyWare respectively. Repeatability was similar for all methods within the same dimension, when compared between 2D and 3D (all p > 0.28). For the 2D RSA methods, accuracy was below 0.055 mm and at least 0.335 mm for PolyWare. For 3D measurements, accuracy was 0.1 mm, 0.2 mm, and 0.3 mm for EGS-RSA, MB-RSA and PolyWare respectively. PolyWare was less accurate compared with RSA methods (p = 0.036). No difference was observed between the RSA methods (p = 0.10). CONCLUSIONS: For all methods, precision and accuracy were better in 2D, with RSA methods being superior in accuracy. Although less accurate and precise, 3D RSA defines the clinically relevant wear pattern (multidirectional). PolyWare is a good and low-cost alternative to RSA, despite being less accurate and requiring a larger sample size.

Ultrasound and MRI measurements of joint cartilage in healthy children: a validation study.

PURPOSE: In juvenile idiopathic arthritis (JIA), proliferative changes in the synovium and synovial fluid accumulation are pathological findings responsible for damage to the cartilaginous tissue and periarticular bone, which are late radiographic findings in conventional radiography. Early detection of these joint changes would allow the clinicians to initiate relevant therapies as is essential for the long-term outcome of JIA. Ultrasonography (US) has shown great potential for this purpose but validation in a pediatric setting is needed. The objective of this study was to validate US measurements of cartilage thickness in target joints in healthy children by comparing them with MRI. MATERIALS AND METHODS: Twenty-five healthy Caucasian children (17 boys/ 8 girls), mean age 11.33 years, were examined with MRI (1.5 T, fat-suppressed T 1-weighted 3D sequences) and US (real-time Hitachi EUB 6500 CFM, B-mode 6 - 14 MHz linear transducer) in the right knee, ankle, wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. US was obtained according to the EULAR standard scans. RESULTS: All differences in cartilage thickness measurements between MRI and US were less than 0.5 millimeters. The coefficient of variation (CV) was found to be good (16 %) except for in the case of the wrist joint (20 %). CONCLUSION: We found a good level of agreement and no significant systematic joint size-related differences in cartilage thickness measurements between MRI and US. US appears to be a feasible method for evaluating cartilage thickness in JIA target joints, especially when age and sex-related references are defined.

Ultrasonography in evaluation of Achilles and patella tendon thickness.

UNLABELLED: Despite the general acknowledgement that measurement of tendon thickness by ultrasonography (US) is an integral part of clinical examination of tendons in both symptomatic and asymptomatic athletes, there is no consensus on where and how the tendons should be measured. PURPOSE: This study aims to evaluate the Achilles and patellar tendons by ultrasonography with the intention of establishing a consensus for measuring the thickness of Achilles and patellar tendons in future studies. MATERIALS AND METHODS: This study includes three sub-studies, evaluating: 1. Achilles and patellar tendon thickness in relation to the distance from the attachment at the calcaneus or patella, 2. longitudinal versus transversal US scan for measurement of the tendon thickness by examining the tendons in both longitudinal and transversal scan planes twice by the same observer, and 3. differences in tendon thickness using three different US measurement methods, when measuring both the sagittal AP thickness and the "true" thickness (measured perpendicular to the greatest width) twice by the same observer. A total of 209 tendons were included. RESULTS: Normal Achilles tendons have the same thickness in the distal 5 cm-long section. Patellar tendons are more cone-shaped proximally. There is no significant difference between the longitudinal and transversal scan except when applied on abnormal patellar tendons. The tendon thickness and coefficient of variation is smaller when measuring the true thickness compared to the AP thickness. CONCLUSION: The true tendon thickness is less than the AP thickness, because the AP-thickness is dependent upon the rotation of the tendon. Moreover, the true thickness is a more precise measurement. In future measurements, the true thickness of tendons could be measured in either transversal or longitudinal scan. When measuring abnormal patellar tendons, however, it is necessary to apply a longitudinal scan as this is the only method allowing the examiner to record the distance from the point where the thickness is measured to the bony attachment. The measurement can thereby be repeated at exactly the same point during subsequent controls.

Efficacy of multimodal optimization of mobilization and nutrition in patients undergoing hip replacement: a randomized clinical trial.

BACKGROUND: The aim of this trial was to assess the effects of optimization of mobilization and nutrition on patients undergoing primary total hip replacement (THR). METHODS: Seventy-nine patients undergoing elective primary THR were recruited prospectively. After randomization, one group received optimized pre-operative information and enforced mobilization and nutrition, another group received conventional peri-operative care. Epidural anaesthesia and post-operative epidural analgesia with local anaesthetics and opioids were used in all cases. Outcome related to length of stay, complications, pain, mobilization, energy intake, and physical activities of daily living (PADL). RESULTS: Although mobilization and nutrition were highly significantly increased in the intervention group, the reduction in length of stay was moderate (7.0 vs. 8.0 days P = 0.019). We found no differences between groups in relation to complications or pain. In the intervention group, the median day of independence in PADL was the third post-operative day (2 : 6 day) and the fourth post-operative day (2 : 7 day) in the control group. The difference was not significant. CONCLUSION: Compared with conventional care, optimal and aggressive nutrition and mobilization resulted in a very moderate reduction in length of stay. There were no differences regarding pain, complications or time until independence in PADL.

Evidence that acute hyperinsulinaemia increases the cytokine content in essential organs after an endotoxin challenge in a porcine model.

BACKGROUND: Insulin has anti-inflammatory effects, as evaluated by its ability to reduce the plasma concentrations of cytokines. However, the inflammatory processing at the organ level is far less well established. The cytokine content in several organs after endotoxin (lipopolysaccharide, LPS) exposure and the effect of hyperinsulinaemia was examined. METHODS: Pigs (35-40 kg) were randomized into four groups, anaesthetized and mechanically ventilated for 570 min: group 1 (anaesthesia only; n = 10), group 2 (hyperinsulinaemic euglycaemic clamp, HEC; n = 9), group 3 (LPS; n = 10) and group 4 (LPS + HEC; n = 9). LPS was infused intravenously for 180 min (total dosage, 10 microg/kg). At the end of the study, i.e. 330 min after the termination of LPS or equivalent, cytokine mRNA and cytokine protein contents in the lungs, heart, liver, adipose tissue and spleen were measured. RESULTS: Hyperinsulinaemia led to increased interleukin-10 (IL-10) protein content in the heart and liver (by 40% and 28%, respectively) in comparison with normoinsulinaemic animals (P < 0.01 and P = 0.02, respectively), and increased tumour necrosis factor-alpha (TNF-alpha) protein content in the heart (P = 0.02). Animals exposed to LPS exhibited reduced TNF-alpha, IL-6 and IL-8 protein content in the heart (P = 0.02, P < 0.001 and P = 0.01, respectively). In the kidneys and adipose tissue, a particularly large cytokine protein content was observed. CONCLUSION: The findings strongly substantiate the role of insulin as an immune-modifying hormone at organ level during baseline and after an endotoxin challenge. Moreover, the kidneys and adipose tissue appear to be pivotal organs in terms of cytokine content shortly after endotoxin exposure, but the complexity remains to be clarified.

Inflammatory response during hyperglycemia and hyperinsulinemia in a porcine endotoxemic model: the contribution of essential organs.

BACKGROUND: During euglycemia acute hyperinsulinemia diminishes the cytokine response to endotoxin [Lipopolysaccharide (LPS)] exposure. In this study we elucidated whether acute hyperglycemia and hyperinsulinemia modify the cytokine content in several organs during LPS challenge in a porcine model. METHODS: Pigs (35-40 kg) were randomized to either normoglycemia (group 1, n = 8) or hyperglycemia and hyperinsulinemia (group 2, n = 8), anesthetized and mechanically ventilated. Both groups received a 180-min intravenous infusion of LPS (total 10 microg kg(-1)). Groups 1 and 2 were clamped at plasma glucose concentrations of 5 mM and 15 mM, respectively. Group 1 maintained a baseline insulin level while the hyperglycemic group exhibited increased insulin levels. RESULTS: Circulating cytokines, cytokine mRNA and cytokine protein content were examined in the heart, liver, kidneys, lungs, spleen, adipose and muscle tissue. After LPS exposure, in both groups vast and equal plasma cytokines were elicited by approximately 70-5000-fold. A 10-fold higher level of IL-10, IL-6 and TNF-alpha protein was found in kidney tissue compared to the other organs together with a 3-10-fold increase of TNF-alpha in adipose tissue. However, cytokine mRNAs as well as organ function were without statistical difference between the groups. CONCLUSION: Endotoxemia elicited a pronounced cytokine response in both plasma and at organ level. The kidneys and adipose tissue showed the highest cytokine protein content. Acute hyperglycemia apparently counteracts the well-established anti-inflammatory effects of insulin on the inflammatory response in a LPS challenged porcine model. Whether the observation can be extrapolated to more long-term stress-exposure remains to be clarified.

Nasal patency is related to dust exposure in woodworkers.

OBJECTIVES: A cross sectional study of 54 furniture factories and three control factories was conducted to investigate the relation between subjective and objective nasal obstruction and exposure to wood dust. METHODS: Acoustic rhinometry was performed on 161 woodworkers and 19 controls. For each person, four measuring rounds were performed: before work, after 4 hours of work, and after 7 hours of work before and after decongestion. Before the first and third measuring round, each person rated the current feeling of nasal obstruction in the left and right nostril separately, using a visual analogue scale. Personal passive dust measurements were performed on 140 woodworkers. RESULTS: The mean (SD) of equivalent inhalable dust was relatively low, 1.17 (0.62) mg/m(3), range 0.17-3.44 mg/m(3). The exposure was divided into four levels: controls, low exposure, medium exposure, and high exposure. For the two highest concentrations of exposure, a significant increase in congestion--decreased nasal cavity volume and cross sectional areas--was found after 4 and 7 hours of work, compared with before work. Multivariate linear regression analysis showed positive correlations between concentration of dust and change in mucosal swelling. A significant increase in self rated nasal obstruction was found after work compared with before work for the two highest exposure groups. No correlation between objective nasal variables and self rated nasal obstruction was found. CONCLUSION: Exposure to wood dust was related in a dose dependent manner to acute nasal obstruction measured by acoustic rhinometry and self reported obstruction, but no correlation was found between measured and self reported obstruction.

Impact of bulk cardiac motion on right coronary MR angiography and vessel wall imaging.

The purpose of this study was to investigate the impact of in-plane coronary artery motion on coronary magnetic resonance angiography (MRA) and coronary MR vessel wall imaging. Free-breathing, navigator-gated, 3D-segmented k-space turbo field echo ((TFE)/echo-planar imaging (EPI)) coronary MRA and 2D fast spin-echo coronary vessel wall imaging of the right coronary artery (RCA) were performed in 15 healthy adult subjects. Images were acquired at two different diastolic time periods in each subject: 1) during a subject-specific diastasis period (in-plane velocity <4 cm/second) identified from analysis of in-plane coronary artery motion, and 2) using a diastolic trigger delay based on a previously implemented heart-rate-dependent empirical formula. RCA vessel wall imaging was only feasible with subject-specific middiastolic acquisition, while the coronary wall could not be identified with the heart-rate-dependent formula. For coronary MRA, RCA border definition was improved by 13% (P < 0.001) with the use of subject-specific trigger delay (vs. heart-rate-dependent delay). Subject-specific middiastolic image acquisition improves 3D TFE/EPI coronary MRA, and is critical for RCA vessel wall imaging.

The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure.

INTRODUCTION: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal models which reflect the disease process. MATERIAL AND RESULTS: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In both groups, histomorphometry revealed markedly increased muscularity of the intra-acinar pulmonary arteries. Circulating levels of endothelin were normal in the shunted animals, and elevated in those with ligation of the left pulmonary artery. CONCLUSION: In neonatal porcine models of pulmonary vascular disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascular disease in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations.

Self-management of oral anticoagulant therapy for mechanical heart valve patients.

OBJECTIVE: Self-management of oral anticoagulant therapy (OAT) has shown good results on a short-term basis. We hypothesize that self-management of OAT provides a better quality of treatment than conventional management also on a long-term basis. The aim of this study was to assess the quality of self-management of OAT in patients with mechanical heart valve prostheses on a 4-year perspective in a prospective, non-randomized study. DESIGN: Twenty-four patients with mechanical heart valves and on self-managed OAT were followed for up to 4 years. A matched, retrospectively selected group of conventionally managed heart valve patients (control group) was used as reference. RESULTS: The median observation time was 1175 days (range: 174-1428 days). The self-managed patients were within therapeutic INR target range for a mean of 78.0% (range: 36.1%-93.9%) of the time compared with 61.0% (range 37.4%-2.9%) for the control group. CONCLUSION: Self-management of OAT is a feasible and safe concept for selected patients with mechanical heart valve prostheses also on a long-term basis. It provides at least as good and most likely better quality of anticoagulant therapy than conventional management assessed by time within the therapeutic International Normalized Ratio (INR) target range.

Three-dimensional echocardiography with tissue harmonic imaging shows excellent reproducibility in assessment of left ventricular volumes.

We studied the reproducibility of repeated measurements of left ventricular (LV) volumes by 2-dimensional (biplane method of disks) and 3-dimensional echocardiography (coaxial scanning) with tissue harmonic imaging. Ten healthy subjects underwent estimation of LV volumes by transthoracic echocardiography twice within 1 week by 2 different operators to investigate interexamination and operator variance. In addition, the analysis of LV volume was done manually by 2 observers to assess both interobserver and intraobserver variances. With 3D echocardiography, observer variation had the greatest impact on variance. Operator variability showed important contributions to total variance with the use of 2D echocardiography. The reproducibility of 3D echocardiography and tissue harmonic imaging is excellent and comparable to magnetic resonance imaging techniques; 3D echocardiography therefore should provide a powerful tool for noninvasive LV volume estimation.

Cardiopulmonary bypass elicits a pro- and anti-inflammatory cytokine response and impaired neutrophil chemotaxis in neonatal pigs.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and organ dysfunction, especially in children. Plasma concentration of inflammatory markers are increased in response to the trauma of cardiac surgery and CPB. The aim of the present study was to investigate whether the CPB procedure in itself elicits increased levels of inflammatory markers in neonatal pigs. METHODS: The inflammatory response was measured in piglets undergoing sternotomy alone (sham group, n=13) or sternotomy and CPB (n=14). Inflammatory mediators were measured at baseline and at fixed time-points during and after CPB. IL-8, IL-10 and TNF-alpha levels and C-reactive protein (CRP) concentrations were measured in plasma samples. Polymorphonuclear neutrophils (PMN) chemotaxis was measured ex vivo, and CD-18 expression using an immunofluorescence technique. RESULTS: Immediately after the CPB procedure increased IL-8 levels were found in the CPB group, but not in sham operated animals (P=0.005). Simultaneously, a marked IL-10 response was measured in the CPB group. Concurrently, PMN chemotaxis decreased in CPB animals but not in the sham group (P=0.04). CD-18 expression and CRP levels were not significantly different between groups and TNF-alpha showed no changes in either group. The chemotactic response did not correlate with plasma IL-8 or IL-10, nor with CD-18 expression. CONCLUSION: The CPB procedure elicited a systemic inflammatory response in terms of significantly elevated plasma levels of IL-8 and IL-10. Furthermore, a temporary and simultaneous decrease in PMN chemotaxis was observed immediately after CPB.

A meta-analysis of cerebrovascular disease and hyperhomocysteinaemia.

Hyperhomocysteinaemia has been identified as a risk factor for stroke and cerebrovascular disease in several studies. To evaluate the evidence we performed a meta-analysis. We found 21 studies searching Medline from 1966-July 1999 using the key words homocysteine, homocystine and cerebrovascular disease or stroke combined with a search of Embase, Science Citation Index and Biological Abstract. In 17 of these studies the populations were comparable. The studies were divided into two groups, cross-sectional studies and longitudinal studies where a pre-insult plasma or serum total homocysteine was used. The reports on 8 cross-sectional and 4 longitudinal studies gave data on the mean and standard deviations of plasma or serum homocysteine for both cases and controls, and these studies were included in the meta-analysis. The results of the 5 excluded studies all pointed to a positive relationship between hyperhomocysteinaemia and cerebrovascular disease. For each study, the expected fractions of the cases with total homocysteine higher than the 95-percentile for the controls were calculated, using the means and standard deviations, assuming a log-normal distribution, and the odds-ratios for disease with total homocysteine above the 95-percentile were computed. The overall weighted odds-ratio for disease with a concentration of homocysteine in plasma or serum above the 95-percentile (95% confidence interval) for the cross-sectional studies was 4.12 (2.94-5.77), for the longitudinal studies 3.74 (2.53-5.54), and for all 12 studies 3.97 (3.07-5.12). In conclusion, the results support the case for a strong relation between hyperhomocysteinaemia and cerebrovascular disease.

Chordal force distribution determines systolic mitral leaflet configuration and severity of functional mitral regurgitation.

OBJECTIVES: The purpose of this study was to investigate the impact of the chordae tendineae force distribution on systolic mitral leaflet geometry and mitral valve competence in vitro. BACKGROUND: Functional mitral regurgitation is caused by changes in several elements of the valve apparatus. Interaction among these have to comply with the chordal force distribution defined by the chordal coapting forces (F(c)) created by the transmitral pressure difference, which close the leaflets and the chordal tethering forces (FT) pulling the leaflets apart. METHODS: Porcine mitral valves (n = 5) were mounted in a left ventricular model where leading edge chordal forces measured by dedicated miniature force transducers were controlled by changing left ventricular pressure and papillary muscle position. Chordae geometry and occlusional leaflet area (OLA) needed to cover the leaflet orifice for a given leaflet configuration were determined by two-dimensional echo and reconstructed three-dimensionally. Occlusional leaflet area was used as expression for incomplete leaflet coaptation. Regurgitant fraction (RF) was measured with an electromagnetic flowmeter. RESULTS: Mixed procedure statistics revealed a linear correlation between the sum of the chordal net forces, sigma[Fc - FT]S, and OLA with regression coefficient (minimum - maximum) beta = -115 to -65 [mm2/N]; p < 0.001 and RF (beta = -0.06 to -0.01 [%/N]; p < 0.001). Increasing FT by papillary muscle malalignment restricted leaflet mobility, resulting in a tented leaflet configuration due to an apical and posterior shift of the coaptation line. Anterior leaflet coapting forces increased due to mitral leaflet remodeling, which generated a nonuniform regurgitant orifice area. CONCLUSIONS: Altered chordal force distribution caused functional mitral regurgitation based on tented leaflet configuration as observed clinically.

[Self management of peroral anticoagulant therapy in patients with artificial heart valves]. / Selvstyring af peroral antikoagulationsbehandling hos patienter med kunstige hjerteklapper.

Twenty-one heart valve operated patients (age 19-70 years) were trained in self-managed oral anticoagulant therapy using a home coagulometer (CoaguChek). Twenty patients accomplished between eight and 29 (median 24) months of self management and were fully capable of self management after 30 weeks of training. No patients experienced major bleeds or thrombo-embolic events. A control group of 20 patients from our department was matched, retrospectively, to the study group. The self-managing patients were within the therapeutic INR range 78% of the study period compared to 54% for the control patients. All self-managing patients had their median INR-value within the therapeutic range, versus only 14 in the control group. Self-management of oral anticoagulant therapy seems feasible for selected patients.

Practicability of patient self-testing of oral anticoagulant therapy by the international normalized ratio (INR) using a portable whole blood monitor. A pilot investigation.

The prophylactic efficacy of long-term oral anticoagulant treatment (OAT) has been demonstrated in a number of clinical conditions with increased tendency to thromboembolism, and the number of individuals subjected to OAT in the industrialised world has increased substantially in recent years. Since this therapy requires considerable resources from both the health care system and the patients, the feasibility of patients' self-monitoring and self-management of OAT has been investigated (1,2,3). The anticipated advantages of this approach include improved convenience and compliance for the patient, who may increase his apprehension for managing the treatment. In addition, self-testing allows for more frequent control compared to the conventional out-patient approach. Importantly, a prerequisite for conceiving a safe and operational concept for patient self-management (PSM) is the availability of a portable INR monitoring system with an accuracy, precision, reproducibility, and long-term reliability comparable to standard coagulometric equipment. The purpose of the present study was to evaluate the feasibility of a commercially available INR-monitor. CoaguChek, for patient self-testing, through a step-wise investigation of the performance characteristics of the equipment in the laboratory, in command of the patient, and during self-testing and self-adjustment of treatment at home. Laboratory INR values were used as reference.

Human response to varying concentrations of toluene.

Thirty two males and 39 females aged 31-50 were exposed for 7 h to one of the three following conditions: (1) Clean air, (2) constant exposure to 100 ppm toluene, or (3) a varying exposure with the same time-weighted average, but with peaks of 300 ppm every 30 min. During exposure the subjects exercised in three 15-min periods with a load of 50 to 100 W. Exposure to toluene caused significant (P less than 0.05) complaints about poor air quality, altered temperature and noise perception, increased irritation in the nose and the lower airways, feeling of intoxication, and there were tendencies (P less than 0.1) towards irritation in the throat, headache and dizziness. In the four performance tests there was a tendency towards a lower score in a vigilance test while no effect of toluene exposure was seen in a peg board test, a five choice serial reaction test, or a colour test, indicating only minimal if any effect on the psychomotor or visual performance. There was no difference in the acute effects caused by the exposure containing peak concentrations and by the constant exposure.

Toluene metabolism during exposure to varying concentrations combined with exercise.

The urinary excretion of hippuric acid (HA) and ortho-cresol (O-cr) in man was measured in two studies of 7-h exposure to toluene in a climate chamber, either constant concentration of 100 ppm or varying concentrations containing peaks of 300 ppm but with a time-weighted average of 100 ppm. In Study A, four males were exposed to clean air and to constant and varying concentrations of toluene in combination with rest and with 100 W exercise in 140 min. Exercise increased end exposure excretion rate of HA and O-cr by 47 and 114%, respectively. After exposure, all excess HA was excreted within 4 h, while O-cr was eliminated with a half life of about 3 h. Alveolar air concentration of toluene varied between 21 and 31 ppm during constant exposure and between 13 and 57 ppm during varying exposure, but no difference in mean alveolar toluene concentration or in metabolite excretion was seen between the exposure schedules. In Study B, 32 males and 39 females aged between 31 and 50 years were exposed once to either clean air, constant or varying concentrations of toluene. Background excretion rate of HA was 0.97 +/- 0.75 mg/min (1.25 +/- 1.05 g/g creatinine) and rose to 3.74 +/- 1.40 mg/min (3.90 +/- 1.85 g/g cr) during the last 3 h of exposure to 100 ppm toluene. The corresponding figures for O-cr were 0.05 +/- 0.05 micrograms/min (0.08 +/- 0.14 mg/g cr), and 2.04 +/- 0.84 micrograms/min (2.05 +/- 1.18 mg/g cr). The individual creatinine excretion rate was considerably influenced by sex, body weight and smoking habits, thus influencing the metabolite concentration standardised in relation to creatinine. It is concluded that both metabolites are estimates of toluene exposure. O-cr is more specific than HA, but the individual variation in excretion of both metabolites is large, and when implementing either of them as biological exposure indices, the influence of sex, body size, age as well as consumption of tobacco and alcohol has to be considered.