Biomedical subjects
Publications and source records attributed to Søren Møller.
Cyanide is a toxic compound which inhibits the cellular utilization of oxygen. A number of substances can give rise to cyanide intoxication, which in some cases may have a delayed onset. The symptoms are non-specific and reflect cellular hypoxia. Several strategies may be employed in the treatment. Hydroxycobalamine is an effective and non-toxic antidote. On the basis of a case story, the toxicology, symptoms and treatment of cyanide poisoning are discussed.
The size of the central and arterial blood volume (CBV) is essential in the understanding of fluid retention in cirrhosis. Previously, it has been reported decreased, normal, or increased, but no reports have analyzed CBV with respect to gender and lean body mass. The aim of the present study was by means of an optimized technique to reassess it in a large group of patients with cirrhosis compared with healthy controls and matched controls in relationship to their body dimensions and gender. Eighty-three patients with cirrhosis (male/female, 60:23), 67 patients without liver disease (male/female, 22:45), and 14 young healthy controls (male/female, 6:8) underwent a hemodynamic investigation with determination of cardiac output, central circulation time, and CBV determined according to kinetic principles. Related to gender, CBV was lower in male cirrhotics (1.48 +/- 0.30 liter) than in matched and young controls (1.68 +/- 0.33 and 1.72 +/- 0.33 liter, respectively; P < 0.05-0.01). No significant differences in CBV were seen between female cirrhotics and controls. Absolute and adjusted CBVs were lower in the females than in men with cirrhosis (P < 0.001), and men with cirrhosis had lower absolute and body weight-adjusted CBVs than matched controls (P < 0.01). Normalized values of CBV (%total blood volume) were significantly lower in patients with cirrhosis (25 +/- 4%) than in matched controls (31 +/- 7%) and young controls (28 +/- 4%; P < 0.02). CBV correlated significantly with anthropometrics, including lean body mass (r = 0.68-0.82; P < 0.0001). In conclusion, the CBV of patients with cirrhosis was lower than that of controls when adjusted for body dimensions and gender. There are significant gender differences, and signs of underfilling are more pronounced in male than in female patients. The results emphasize the importance of adjustments of blood volumes for anthropometrics and gender.
BACKGROUND/AIMS: The aim of the study was to investigate the effect of a standard albumin load on blood volume distribution, arterial compliance, and the renin-angiotensin-aldosterone system in patients with different degrees of cirrhosis. METHODS: 31 patients with cirrhosis (Child classes A/B/C=8/14/9) received an intravenous infusion of 40 g human serum albumin during a haemodynamic investigation. RESULTS: Whereas plasma- and blood volume increased by 23 and 15%, respectively (P<0.001), a significant increase in central blood volume was found only in class A patients (+8%, P<0.05), but not in class B or class C patients (+2.7%, not significant (n.s.)). In contrast, arterial compliance only increased significantly in class C patients (+18%, P<0.05), but not in class A or class B patients (+6%, n.s.). Plasma renin activity (PRA) decreased significantly in class C patients (-31%, P<0.05). When all patients were compared, the change in arterial compliance was inversely correlated to the change in PRA (r=-0.50, P<0.01). CONCLUSIONS: Although infusion of albumin does not expand the central blood volume in patients with advanced cirrhosis, the results indicate a significant improvement in the low effective arterial blood volume of such patients, which may be important in the prevention of circulatory dysfunction.
BACKGROUND/AIMS: Measurement of cardiac output in hyperkinetic patients with cirrhosis by Doppler echocardiography is increasingly reported, but has not been validated. We have compared simultaneous measurements of cardiac output by Doppler echocardiography (CO(d)) and by the indicator dilution technique (CO(I)). METHODS: Twelve patients with cirrhosis were studied. CO(d) was measured as the spatial mean velocity of the left ventricular outflow tract, multiplied by the cross-sectional area and the heart rate. CO(I) was determined by the standard indicator dilution technique after injection of 125I albumin and 99mTc albumin into the right atrium and subsequent sampling from the femoral artery. RESULTS: The mean CO(d) and CO(I) were similar (7.20 vs 7.15 l/min, NS). A highly significant correlation was present between CO(d) and CO(I) (r = 0.86, P < 0.0001; slope 0.91, Y(0) = 0.78 l/min). However, the mean squared difference between CO(d) and CO(I) was 2.3 (l/min)2. A Bland-Altman plot revealed no trend with the level of cardiac output. The standard deviation (0.79 vs 0.30 l/min, P < 0.01) and the coefficient of variation (10.5 vs 4.2%, P < 0.01) of duplicate measurements were significantly higher with the Doppler technique. CONCLUSION: Doppler measurements of cardiac output in groups of patients with cirrhosis are accurate with respect to the group mean, but marked disagreements of over- and underestimation were seen in individual patients. The reproducibility of the Doppler technique is acceptable, although not as good as that of the indicator dilution technique.
Locked nucleic acid (LNA) is a new class of bicyclic high affinity DNA analogs. LNA-containing oligonucleotides confer significantly increased affinity against their complementary DNA targets, increased mismatch discrimination (delta Tm) and allow full control of the melting point of the hybridization reaction. LNA chemistry is completely compatible with the traditional DNA phosphoramidite chemistry and therefore LNA-DNA mixmer oligonucleotides can be designed with complete freedom for optimal performance. These properties render LNA oligonucleotides very well suited for SNP genotyping and have enabled several approaches for enzyme-independent SNP genotyping based on allele-specific hybridization. In addition, allele-specific PCR assays relying on enzymatically-enhanced discrimination can be improved using LNA-modified oligonucleotides. The use of LNA transforms enzyme-independent genotyping approaches into experimentally simple, robust and cost-effective assays, which are highly suited for genotyping in clinical and industrial settings.
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BACKGROUND/AIMS: Previous investigations have shown a prolonged QT interval in some patients with cirrhosis. The aim of this study was to investigate the relation between electrical and mechanical systole in patients with different degrees of severity of cirrhosis. METHODS: Forty-eight patients with cirrhosis and portal hypertension, studied during a haemodynamic investigation, were compared to 17 controls. RESULTS: A prolonged QTc (above 0.440 s(1/2)) was found in 37% of the cirrhotic patients vs. 5.9% in the controls (P=0.03), and there was a correlation to liver dysfunction (P<0.02). A direct relation between QT and time of mechanical systole (tS) was observed in controls (r=0.58, P<0.01), and cirrhotic patients (r=0.44, P<0.002). In patients with a prolonged QTc interval, the difference between electrical and mechanical systole time was substantially longer than in patients with a normal QTc interval (0.078 vs. 0.031 s, P<0.005). The QT values were related to markers of hyperdynamic circulation (r=-0.48 to 0.56, P<0.05-0.001). CONCLUSIONS; Prolonged repolarization, as evidenced by prolonged QTc, is related to both impaired liver function and systemic circulatory dysfunction. In addition these patients have alterations in the cardiac excitation-contraction relation with compromised association between electrical and mechanical function.
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BACKGROUND: Different diagnostic examinations have been applied in the management of patients with suspected intestinal ischaemia. In some centres, invasive determination of a meal-induced increase in splanchnic blood flow is used in the diagnostic process and in the selection of patients for surgery. However, no studies have evaluated the impact of splanchnic blood flow determination on therapy in such patients. OBJECTIVE: The aim of the present study was therefore to analyse the outcome of splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia. METHODS: Seventy-three consecutive patients with suspected intestinal ischaemia were included during a 5-year period. Splanchnic blood flow was determined at baseline and after a standardized meal. The patients were classified into three groups according to the level of meal-induced increase in splanchnic blood flow: A, normal response (splanchnic blood flow > or = 200 ml/min); B, possible abnormal response (splanchnic blood flow 51-199 ml/min); and C, definitive abnormal response (splanchnic blood flow < or = 50 ml/min). Where surgery took place, the type of operation was noted. RESULTS: Forty patients had a normal meal-induced response, 23 patients had a possible abnormal response and 10 patients had a definitive abnormal response, which gave evidence of chronic intestinal ischaemia. In the total patient population, the increase in splanchnic blood flow was significantly correlated to an increase in hepatic oxygen uptake (r = 0.38, P < 0.002) and to body weight (r = 0.36, P < 0.01). A total of seven patients (10%) underwent successful revascularization. CONCLUSIONS: Ten of the patients with suspected chronic intestinal ischaemia had abnormal meal-induced splanchnic blood flow and 30% of these patients underwent angioplasty. Future studies are needed to validate the determination of splanchnic blood flow in relation to splanchnic angiography and other imaging modalities in patients with chronic intestinal ischaemia.
Glucagon-like peptide 1 (GLP-1) is a potent anti-hyperglycemic hormone currently under investigation for its therapeutic potential. However, due to rapid degradation by dipeptidyl peptidase IV (DPP IV), which limits its metabolic stability and eliminates its insulinotropic activity, it has been impossible to assess its true efficacy in vivo. In chloralose-anesthetized pigs given valine-pyrrolidide (to block endogenous DPP IV activity), the independent effects of GLP-1-(7-36) amide on glucose and insulin responses to intravenous glucose were assessed, and the metabolite generated by DPP IV, GLP-1-(9-36) amide, was investigated for any ability to influence these responses. GLP-1-(7-36) amide enhanced insulin secretion (P < 0.03 vs. vehicle), but GLP-1-(9-36) amide was without effect, either alone or when coinfused with GLP-1-(7-36) amide. In contrast, GLP-1-(9-36) amide did affect glucose responses (P < 0.03). Glucose excursions were greater after saline (121 +/- 17 mmol x l(-1) x min) than after GLP-1-(9-36) amide (73 +/- 19 mmol x l(-1) x min; P < 0.05), GLP-1-(7-36) amide (62 +/- 13 mmol x l(-1) x min; P < 0.02) or GLP-1-(7-36) amide + GLP-1-(9-36) amide (50 +/-13 mmol x l(-1) x min; P < 0.005). Glucose elimination rates were faster after GLP-1-(7-36) amide + (9-36) amide (10.3 +/- 1.2%/min) than after GLP-1-(7-36) amide (7.0 +/- 0.9%/min; P < 0.04), GLP-1-(9-36) amide (6.8 +/- 1.0%/min; P < 0.03), or saline (5.4 +/- 1.2%/min; P < 0.005). Glucagon concentrations were unaffected. These results demonstrate that GLP-1-(9-36) amide neither stimulates insulin secretion nor antagonizes the insulinotropic effect of GLP-1-(7-36) amide in vivo. Moreover, the metabolite itself possesses anti-hyperglycemic effects, supporting the hypothesis that selective DPP IV action is important in glucose homeostasis.