Niels Trolle Andersen

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. J. Magn. Reson. Imaging 2001;14:383–390.

Subclinical Coronary and Aortic Atherosclerosis Detected by Magnetic Resonance Imaging in Type 1 Diabetes With and Without Diabetic Nephropathy

Background— Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. Methods and Results— In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7±0.3 versus 1.3±0.2 mm; P<0.001) and maximum right coronary artery wall thickness (2.2±0.5 versus 1.6±0.3 mm; P<0.001), was greater in subjects with nephropathy. The prevalence of thoracic (3% versus 0%; P=0.28) and abdominal aortic plaque (22% versus 16%; P=0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. Conclusions— In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.

Prophylactic Training in Asymptomatic Soccer Players With Ultrasonographic Abnormalities in Achilles and Patellar Tendons The Danish Super League Study

Background A recent study published in The American Journal of Sports Medicine showed that asymptomatic soccer players with an increased risk of developing Achilles and patellar tendon injuries within the next 12 months can be identified with use of ultrasonography. Hypothesis Prophylactic eccentric training and stretching can reduce both the frequency of asymptomatic ultrasonographic changes in Achilles and patellar tendons in soccer players and the risk of these asymptomatic intratendinous changes becoming symptomatic. Study Design Randomized controlled trial; Level of evidence, 1. Methods Two hundred and nine Danish professional soccer players from the best national league (Super League) were followed over 12 months with use of ultrasonography and injury registration. Half the teams were randomized to an intervention group with prophylactic eccentric training and stretching of the Achilles and patellar tendons during the soccer season. Results The eccentric training and stretching did not reduce the injury risk, and, contrary to all expectations, the injury risk during the season was increased in players with abnormal patellar tendons at the beginning of the study in January. Eccentric training and stretching in players with normal patellar tendons significantly reduced the proportion of players with ultrasonographic changes in the patellar tendons at the end of the season (risk difference [RD] = 12%; 95% confidence interval [CI], 2%–22%; P = .02), but the training had no effect on the Achilles tendons (RD = 1%; 95% CI, −7% to 9%; P = .75). The presence of preseason ultrasonographic abnormalities in the tendons significantly increased the risk of developing tendon symptoms during the season (relative risk = 1.9; 95% CI, 1.2–3.1; P = .009). Conclusions This study demonstrates that with the use of ultrasonography, tendon changes in soccer players can be diagnosed before they become symptomatic. The prophylactic eccentric training and stretching program reduces the risk of developing ultrasonographic abnormalities in the patellar tendons but has no positive effects on the risk of injury. On the contrary, in asymptomatic players with ultrasonographically abnormal patellar tendons, prophylactic eccentric training and stretching increased the injury risk.

Acute hyperinsulinemia restrains endotoxin-induced systemic inflammatory response: An experimental study in a porcine model

BackgroundIntensive insulin therapy in critically ill patients reduces morbidity and mortality. The current study elucidates whether acute hyperinsulinemia per se could attenuate the systemic cytokine response and improve neutrophil function during endotoxin (lipopolysaccharide)-induced systemic inflammation in a porcine model. MethodsPigs were anesthetized, mechanically ventilated, randomized into four groups, and followed for 570 min: group 1 (anesthesia solely, n = 10), group 2 (hyperinsulinemic euglycemic clamp [HEC], n = 9), group 3 (lipopolysaccharide, n = 10), group 4 (lipopolysaccharide–HEC, n = 9). Groups 3 and 4 were given a 180-min infusion of lipopolysaccharide (total, 10 &mgr;g/kg). Groups 2 and 4 were clamped (p-glucose: 5 mm/l, insulin 0.6 mU · kg−1 · min−1) throughout the study period. Changes in pulmonary and hemodynamic function, circulating cytokines, free fatty acids, glucagon, and neutrophil chemotaxis were monitored. ResultsTumor necrosis factor &agr; and interleukin 6 were significantly reduced in the lipopolysaccharide–HEC group compared with the lipopolysaccharide group (both P = 0.04). In the lipopolysaccharide–HEC group, the glucagon response was diminished compared with the lipopolysaccharide group (P < 0.05). Serum free fatty acid concentrations were decreased in animals exposed to HEC. Animals receiving lipopolysaccharide showed an increase in pulmonary pressure (P < 0.001), but otherwise, there were no major changes in pulmonary or hemodynamic function. Neutrophil function was impaired after lipopolysaccharide administration. ConclusionHyperinsulinemia concomitant with normoglycemia reduces plasma concentrations of tumor necrosis factor &agr; and the catabolic hormone glucagon in lipopolysaccharide-induced systemic inflammation in pigs. The finding strongly supports the role of insulin as an antiinflammatory hormone. Whether the effect to some extent operates via a reduced free fatty acid concentration is unsettled.

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.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.

Validation of sick leave measures: self-reported sick leave and sickness benefit data from a Danish national register compared to multiple workplace-registered sick leave spells in a Danish municipality

BackgroundPrevious validation studies of sick leave measures have focused on self-reports. Register-based sick leave data are considered to be valid; however methodological problems may be associated with such data. A Danish national register on sickness benefit (DREAM) has been widely used in sick leave research. On the basis of sick leave records from 3,554 and 2,311 eldercare workers in 14 different workplaces, the aim of this study was to: 1) validate registered sickness benefit data from DREAM against workplace-registered sick leave spells of at least 15 days; 2) validate self-reported sick leave days during one year against workplace-registered sick leave.MethodsAgreement between workplace-registered sick leave and DREAM-registered sickness benefit was reported as sensitivities, specificities and positive predictive values. A receiver-operating characteristic curve and a Bland-Altman plot were used to study the concordance with sick leave duration of the first spell. By means of an analysis of agreement between self-reported and workplace-registered sick leave sensitivity and specificity was calculated. Ninety-five percent confidence intervals (95% CI) were used.ResultsThe probability that registered DREAM data on sickness benefit agrees with workplace-registered sick leave of at least 15 days was 96.7% (95% CI: 95.6-97.6). Specificity was close to 100% (95% CI: 98.3-100). The registered DREAM data on sickness benefit overestimated the duration of sick leave spells by an average of 1.4 (SD: 3.9) weeks. Separate analysis on pregnancy-related sick leave revealed a maximum sensitivity of 20% (95% CI: 4.3-48.1).The sensitivity of self-reporting at least one or at least 56 sick leave day/s was 94.5 (95% CI: 93.4 – 95.5) % and 58.5 (95% CI: 51.1 – 65.6) % respectively. The corresponding specificities were 85.3 (95% CI: 81.4 – 88.6) % and 98.9 (95% CI: 98.3 – 99.3) %.ConclusionsThe DREAM register offered valid measures of sick leave spells of at least 15 days among eldercare employees. Pregnancy-related sick leave should be excluded in studies planning to use DREAM data on sickness benefit. Self-reported sick leave became more imprecise when number of absence days increased, but the sensitivity and specificity were acceptable for lengths not exceeding one week.

The effect of pretreating morselized allograft bone with rhBMP-2 and/or pamidronate on the fixation of porous Ti and HA-coated implants.

BMPs stimulate new bone formation, but may also accelerate bone resorption. We added rhBMP-2 and pamidronate to morselized bone allograft packed around uncemented HA-coated and non-coated porous Ti implants in sixteen dogs. Each dog received four implants where the allograft was added (1) nothing, (2) BMP, (3) BP, and (4) BMP+BP. After four weeks, the untreated control implants had better mechanical fixation than all other treatment groups. The rhBMP-2-treated group had abundant formation of new bone on and around the implant. However, almost all allografts were resorbed, rendering the implant mechanically unstable. In the pamidronate-treated group the allograft was preserved, but the implants were covered by fibrous tissue and there was almost no new bone formation. This was also the case for the combined BMP+BP group, although fibrous tissue was absent on these implants. The HA-coated implants had more than twice as good mechanical fixation and improved osseointegration compared to the corresponding Ti implants. RhBMP-2 raised the total metabolic turnover of bone within the allograft with a net negative result on implant fixation. Pamidronate virtually blocked bone metabolism, also when combined with rhBMP-2. The results warrant a conservative approach and emphasize the importance of identifying a therapeutic window for these substances prior to clinical use.

Ultrasonographic Measurements of Joint Cartilage Thickness in Healthy Children: Age- and Sex-Related Standard Reference Values

Objective. Loss of joint cartilage may be an early feature of chronic inflammatory joint diseases like juvenile idiopathic arthritis (JIA). Conventional radiography usually detects only late changes such as joint space narrowing and bone erosion rather than early inflammatory changes. Joint cartilage is easily visualized with high-frequency ultrasonography (US), but age- and gender-related normal standard reference values should be established before US measurement of cartilage thickness becomes standard procedure in the clinic. Methods. A cross-sectional study of bilateral grey-scale US cartilage thickness of the knee, ankle, wrist, and second metacarpophalangeal (MCP) and second proximal interphalangeal (PIP) joints was performed in 394 (215 boys/179 girls) healthy Danish Caucasian children aged between 7 and 16 years. Results. Cartilage thickness differed significantly between sexes (p < 0.001 for all joints), boys having thicker cartilage than girls. Cartilage thickness clearly decreased with increasing age in both sexes. A formula for calculating sex-specific cartilage thickness at different ages in childhood is suggested. No difference between the right and left side of the investigated joints was observed. Conclusion. Using US, we established age- and sex-related normal reference intervals for cartilage thickness of the knee, ankle, wrist, and MCP and PIP joints in 7- to 16-year-old children, and designed a formula for calculating hyaline cartilage thickness in all age groups throughout childhood.

Human response to varying concentrations of toluene

SummaryThirty 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 < 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 < 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.

The Central Limit Theorem and the Law of Iterated Logarithm for Empirical Processes under Local Conditions

SummaryA CLT and a LIL are proved under weak-L2 Gaussian bracketing conditions (weaker than the usual ones). These results have wide applicability and in particular provide an improvement of the Jain-Marcus central limit theorem for C(S)-valued random variables.