Biomedical subjects

N A Klitgaard

Publications and source records attributed to N A Klitgaard.

At least 19 recordsLinked to original sources

PubMed2005

Drugs in injured drivers in Denmark.

As part of the project Impaired Motorists, Methods of Roadside Testing and Assessment for Licensing (IMMORTAL) under the European Commission's Transport RTD Programme of the 5th Framework Programme [I.M. Bernhoft, Drugs in accidents involved drivers in Denmark, D-R4.3 of the project Impaired Motorists, Methods Of Roadside Testing and Assessment for Licensing (IMMORTAL), , 2005], a study regarding drugs in accident-involved drivers was carried out in Denmark. The main objectives of this study were: (1) to collect and analyse samples from injured drivers for the presence of drugs; (2) to give an indication whether drugs may have contributed to traffic accidents; and (3) to get information on the drug-positive drivers and their drug use. This paper focuses on objective 1. Injured drivers who were treated in hospital were asked to give a saliva sample, a blood sample or both. The samples were screened for the following substances: opiates, amphetamines, methamphetamines, incl. MDMA (ecstasy), cannabinoids and metabolites, cocaine and metabolites and benzodiazepines. Screenings were carried out by means of Cozart Microplate EIA kit. Positive screenings were confirmation analysed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography/tandem mass spectrometry (LC/MS/MS). In total, 26 out of 330 patients were confirmed positive for one or more of the six drug groups. However, three patients were excluded from the survey for various reasons. Of the remaining 23 drug-positive patients 15 were found positive for one drug group, and in five of these cases alcohol was present in a concentration over the legal limit in Denmark (0.05%). The other eight patients were found positive for two drug groups, and in four of these cases, alcohol was also present in a concentration over the legal limit. Alcohol was found both in combinations with medicinal drugs, with illegal drugs and with both. Based on the saliva or blood concentrations, we estimate that there is a strong suspicion of impairment in 9 out of 23 cases, and in another six cases it was likely that the drivers were impaired.

Accidents, Traffic↗

PubMed2005

The long-term pharmacokinetics and safety of adding low-dose ritonavir to a nelfinavir 1,250 mg twice-daily regimen in HIV-infected patients.

OBJECTIVES: To evaluate the long-term pharmacokinetics and safety of adding ritonavir 100 mg twice-daily to a nelfinavir 1250 mg twice-daily regimen in HIV-infected patients. METHODS: This was a prospective, randomized, open-label, controlled 24-week study. Sixteen patients receiving a nelfinavir 1250 mg twice-daily regimen with plasma viral load <1000 HIV-1 RNA copies/mL were randomized to continue treatment or to have ritonavir 100 mg twice-daily added. Safety, including fasting lipid levels, was evaluated at weeks 4, 12 and 24. Patients who were randomized to have ritonavir added (n=9) participated in three 12-h pharmacokinetic evaluations at baseline, week 4 and week 24. RESULTS: Increases in median nelfinavir steady-state plasma concentrations at 12 h (C(12)) from 512 to 773 ng/mL [median difference 450 ng/mL; 95% confidence interval (CI) 116--1510 ng/mL] and in median active nelfinavir metabolite M 8 C(12) from 107 to 603 ng/mL (median difference 545 ng/mL; 95% CI 370--891) were seen after the addition of low-dose ritonavir (baseline to week 24). There were no differences between the nelfinavir or M 8 pharmacokinetic parameters at weeks 4 and 24. No significant changes or differences in the concentration of fasting total cholesterol, low-density lipoprotein (LDL) cholesterol or total triglycerides or in the occurrence of adverse events were observed within or between the two groups. CONCLUSIONS: Nelfinavir and especially M 8 concentrations are increased when low-dose ritonavir is added to a nelfinavir-containing regimen. The combination seems to be safe and the nelfinavir/ritonavir regimen could be an option in patients with low nelfinavir+M 8 concentrations.

Adult↗

PubMed2004

Pharmacokinetic interaction between rifampin and the combination of indinavir and low-dose ritonavir in HIV-infected patients.

Rifampin is an important drug in the treatment of tuberculosis, but administration of rifampin in combination with protease inhibitors is complicated because of drug-drug interactions. A prospective, controlled, multiple-dose study involving 6 HIV-infected patients receiving a combination of indinavir (800 mg) and ritonavir (100 mg) twice a day was performed to evaluate whether the inducing effect of rifampin on the drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 could be overcome by the inhibitory effect of ritonavir. Pharmacokinetic evaluations of steady-state concentrations of indinavir and ritonavir were performed before and after administration of rifampin (300 mg every day for 4 days). An 87% reduction (from 837 to 112 ng/mL) in median indinavir and a 94% reduction (from 431 to 27 ng/mL) in median ritonavir concentrations were seen 12 h after the last dose of rifampin was administered (P=.031). These results strongly indicate that the administration of rifampin with a combination of indinavir (800 mg) and ritonavir (100 mg) could lead to subtherapeutic concentrations of indinavir.

Adult↗

PubMed2003

Simultaneous quantitative determination of the HIV protease inhibitors indinavir, amprenavir, ritonavir, lopinavir, saquinavir, nelfinavir and the nelfinavir active metabolite M8 in plasma by liquid chromatography.

A simple HPLC method that quantitates all six currently available protease inhibitors and the nelfinavir active metabolite M8 in one assay is presented. A 500-microliter plasma sample was treated by liquid-liquid extraction with a mixture of heptane and ethyl acetate. After evaporation, the residue was redissolved in sodium dihydrogenphosphate and acetonitrile and washed twice with heptane. Chromatography was performed with an analytical C(18) column. Ultraviolet detection at 210 and 239 nm was used. The present method is associated with high accuracy and low imprecision in the concentration range of 25-5000 ng/ml of all six protease inhibitors and M8. This makes it suitable for monitoring purposes.

Case-Control Studies↗

PubMed2003

Systemic levels of cotinine and elastase, but not pulmonary function, are associated with the progression of small abdominal aortic aneurysms.

OBJECTIVE: to study whether smoking and impaired pulmonary function are associated with the expansion of abdominal aortic aneurysms (AAA). METHODS AND MATERIAL: seventy-nine men with small (3-5 cm), screen-detected AAA underwent a simple 5-step smoking history, measurement of the forced first second expiratory volume (FEV1), venepuncture and annual ultrasound scan for mean follow-up period of 3.5 years. RESULTS: all but one patient had a significantly reduced FEV1 (p<0.05, Mann-Whitney). The FEV1/expected FEV1 ratio (rFEV1) was not related to AAA expansion but was negatively correlated with P-elastase-alpha1-antitrypsin-complexes (P-Elastase). P-Elastase was positively correlated with smoking and S-cotinine. Smoking, S-cotinine, and P-elastase were positively correlated with the mean annual AAA expansion rate but not rFEV1. CONCLUSION: in general, patients with AAA have impaired pulmonary function. A simple five step smoking classification is as predictive of AAA-expansion as S-cotinine. Smoking may cause elastase secretion leading to pulmonary and aortic elastin degradation but the lack of association between AAA-expansion and rFEV1 suggest that other mechanisms are important.

Aged↗

PubMed2001

[Clozapine-induced toxic hepatitis].

A case of clozapine-induced toxic hepatitis in a 49-year old woman with schizophrenia is described. The daily clozapine dose was clinically titrated to 300 mg. Subsequently, the patient experienced lethargy and anorexia, and fever, eosinophilia, leucocytosis and abnormal liver parameters were found. The serum concentration of clozapine was 8595 nmol/l, and treatment was discontinued. After eight days, the condition stabilised, and low-dose clozapine treatment was successfully reinstituted with serum monitoring (TDM).

Chemical and Drug Induced Liver Injury↗

PubMed2001

Magnesium reduces insulin-stimulated glucose uptake and serum lipid concentrations in type 1 diabetes.

A magnesium (Mg) deficit has been described in patients with type 1 diabetes, and it has been related to the development of cardiovascular disease. We tested the hypothesis that type 1 diabetic patients have deficits in dietary Mg intake and that proper long-term (24 weeks) oral Mg supplementation would reduce cardiovascular risk factors. Therefore, the Mg status, dietary Mg intake, and the effect of Mg supplementation were evaluated in 10 type 1 diabetic patients and 5 control subjects. Muscle Mg content was decreased by 7% in the type 1 diabetic patients, and it increased by 5% after 24 weeks of oral MgO supplementation. Acute and chronic Mg supplementation decreased serum total cholesterol, serum low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B. Insulin-stimulated glucose uptake decreased by 35% after 24 weeks of oral MgO supplementation. Eight of 10 patients with type 1 diabetes had a daily intake of Mg below 90% of the recommended daily allowance. In conclusion, a Mg deficit was found in type 1 diabetic patients. The deficit might be due partly to a relatively Mg-deficient diet. Mg repletion was associated with a decrease in atherogenic lipid fractions and a reduced insulin-stimulated glucose uptake.

Adult↗

PubMed2001

Fluvoxamine inhibits the CYP2C9 catalyzed biotransformation of tolbutamide.

OBJECTIVE: Our objective was to examine the interaction between fluvoxamine and tolbutamide to confirm that fluvoxamine inhibits CYP2C9. METHODS: The study was carried out as an open, randomized, crossover design with 14 healthy participants. In period A, all volunteers took 500 mg of tolbutamide orally. In period B, the volunteers were randomly assigned to one of two groups. Each group took either 150 mg or 75 mg of fluvoxamine a day for 5 days (day -3 to day 2). The groups then took 500 mg of tolbutamide as a single dose (day 0). In both periods, blood and urine were sampled at regular intervals. Plasma was analyzed for tolbutamide, and urine was analyzed for tolbutamide and its two metabolites, 4-hydroxytolbutamide and carboxytolbutamide by means of HPLC. RESULTS: During treatment with fluvoxamine, there was a statistically significant decrease in the median of the total clearance of tolbutamide, from 845 mL/h to 688 mL/h, among the volunteers who received 75 mg/d. There was a reduction that reached borderline statistical significance in the group that received 150 mg/d of tolbutamide. The clearance by means of 4-hydroxytolbutamide and carboxytolbutamide was significantly reduced in both groups (ie, from 901 mL/h to 318 mL/h in the group that received 150 mg of tolbutamide per day and from 723 mL/h to 457 mL/h in the group that received 75 mg of tolbutamide per day). Thus there was a tendency toward a more pronounced inhibition of the 4-hydroxylation during treatment with 150 mg/d of fluvoxamine compared with 75 mg/d, but the difference was not statistically significant. CONCLUSION: Fluvoxamine is a moderate inhibitor of CYP2C9 in vivo.

Adult↗

PubMed2001

Specific effect of venlafaxine on single and repetitive experimental painful stimuli in humans.

BACKGROUND: Tricyclic antidepressants relieve neuropathic pain, and the analgesic properties of tricyclic antidepressants are substantiated in human experimental pain models. It has been speculated that drugs with a selective inhibition of presynaptic reuptake of both serotonin and noradrenaline could have an analgesic effect comparable to the analgesic effect of tricyclic antidepressants. OBJECTIVE: Our objective was to evaluate the analgesic effect of the serotonin-noradrenaline reuptake inhibitor venlafaxine in human experimental pain models. METHOD: The study was carried out as a randomized, placebo-controlled, double-blind, crossover experiment that included 16 healthy volunteers. A 37.5-mg dose of venlafaxine was given orally 4 times with 12-hour intervals, and pain tests were performed before and 3 hours after the second and fourth doses. Pain tests included the determination of pain detection and tolerance thresholds to pressure, pain detection and tolerance thresholds on single electrical transcutaneous stimulation of the sural nerve, pain temporal summation on repetitive electrical sural nerve stimulation, and pain experienced during the cold pressor test. RESULTS: Venlafaxine increased thresholds for pain tolerance after single electrical stimulation (P =.005) and pain summation (P =.01) on repetitive stimulation but did not alter the thresholds for pain detection after single electrical sural nerve stimulation. Venlafaxine did not alter pain experienced during the cold pressor test or increase the pressure pain thresholds. CONCLUSION: Venlafaxine increases the pain tolerance threshold to electrical sural nerve stimulation and the threshold at which pain increases (pain summation). The impact of venlafaxine on pain summation in this experimental pain model on repetitive stimulation may indicate a potential analgesic effect for clinical neuropathic pain.

Adult↗

PubMed2001

Muscle sodium, potassium, and [(3)H]ouabain binding in identical twins, discordant for type 2 diabetes.

A reduced functional capacity of the sodium (Na), potassium (K) pump might reduce energy expenditure, inducing obesity and type 2 diabetes. Consequently, the Na and K content and [(3)H]ouabain binding capacity of skeletal muscle were measured in 10 monozygotic twin pairs discordant for type 2 diabetes and in 10 obese controls. Muscle [(3)H]ouabain binding capacity was reduced by approximately 20% in type 2 diabetes. Removing the genetic component by looking at differences within twin pairs, the difference in waist/hip ratio was associated with the difference in [(3)H]ouabain binding (r = -0.85; P < 0.002). Except for the type 2 diabetic twins in the basal state, both basal and insulin-stimulated energy expenditure were associated with the muscle K/Na ratio in the twins. In controls, the 2-h plasma glucose concentration during an oral glucose tolerance test was associated with the change in both muscle and plasma K induced by a euglycemic, hyperinsulinemic clamp. In conclusion, environmental factors related to the waist/hip ratio reduce the muscle [(3)H]ouabain binding capacity in type 2 diabetes. Without proving causality, the muscle K/Na ratio is associated with energy expenditure in individuals genetically predisposed to the development of type 2 diabetes.

Adult↗

PubMed2000

Hyperglycaemia enhances renal magnesium excretion in type 1 diabetic patients.

Magnesium depletion is a common feature of diabetes mellitus, apparently related to glycaemic control. The aim of the study was to investigate the isolated effect of hyperglycaemia upon renal magnesium excretion. Urinary magnesium excretion rates were measured in 10 patients with Type 1 diabetes mellitus on two different days with different levels of blood glucose concentration but equal plasma insulin concentration. On a hyperglycaemic day, an i.v. infusion of 20% glucose was started at the end of a euglycaemic baseline period, increasing blood glucose concentration from 5.3 mmol/L to 12.3 mmol/L. There was no major glucosuria. On the hyperglycaemic day the renal magnesium excretion and clearance were raised by a factor of 2.4 compared to the euglycaemic day. Plasma magnesium concentration decreased 3% during hyperglycaemia. In conclusion, blood glucose excursions influence magnesium homeostasis independently of insulin levels in Type 1 diabetic patients. This effect is primarily due to an increased renal magnesium clearance during hyperglycaemia.

Adult↗

PubMed2000

Saliva and serum concentration of lamotrigine in patients with epilepsy.

The authors examined the interindividual correlation between saliva and serum concentrations of lamotrigine (LTG) and the relationship between LTG concentration in saliva and the free LTG concentration in serum in 40 patients with epilepsy, aged 16 to 73 years, receiving stable doses of LTG and comedication. Saliva was collected before and after stimulation of salivary flow. The free LTG fraction was determined by equilibrium dialysis and ultrafiltration. Drug analysis was performed by high-performance liquid chromatography. The correlation between LTG daily dose and serum concentration was weak but significant (r = 0.47). There was high correlation between LTG concentration in serum and unstimulated (r = 0.85) or stimulated (r = 0.94) saliva, and between total LTG concentration in serum and the free LTG fraction as determined by ultrafiltration (r = 0.95) and equilibrium dialysis (r = 0.93). Lamotrigine concentration in stimulated saliva was significantly correlated to the free LTG fraction. Protein binding of LTG calculated from concentration in stimulated saliva, as determined by ultrafiltration and equilibrium dialysis, was 51.8% +/- 13.03%, 68.05% +/- 7.59%, and 58.72% +/- 7.68% (mean +/- standard deviation) respectively. The differences between the three methods were significant. The authors conclude that saliva sampling may be a useful alternative to blood tests for monitoring LTG treatment.

Adolescent↗

PubMed1999

Correlation between serial changes in left-sided heart chambers and atrial natriuretic peptide and N-terminal pro atrial natriuretic peptide after a first myocardial infarction. An echocardiographic study.

Dilatation of the left ventricle predicts morbidity and mortality after acute myocardial infarction. We compared serial echocardiographic examinations of the left atrium and ventricle with measurements of plasma atrial natriuretic peptide (ANP) and plasma N-terminal pro atrial natriuretic peptide (NT-proANP) in 22 patients during the first 6 months following a first myocardial infarction. ANP, but not NT-proANP, was found to be significantly correlated to the diastolic/systolic size of the left atrium (r = 0.58/0.60) and the systolic size of the left ventricle (r = 0.43) in the acute phase 2-4 days after infarction. At 10-12 days after the infarction, we found a significant correlation between all sizes of the left-sided chambers and ANP, whereas NT-proANP only correlated with the left atrial sizes. Three months after the infarction, all sizes of the left-sided chambers correlated with both ANP and NT-proANP, with the exception of a non-significant correlation between NT-proANP and the left atrial diastolic size. After 6 months only the area of the diastolic and systolic left atrium correlated with plasma ANP and only the systolic size of the left atrium correlated with NT-proANP. The percentage change in the size of the left atrium, but not the left ventricle, correlated significantly with the percentage change in both ANP (r = 0.57) and NT-proANP (r = 0.70). We conclude that the distension of the left atrium rather than the dilatation of the left ventricle is related to the concentration of ANP and NT-proANP after an acute myocardial infarction.

Adult↗

PubMed1999

Effect of moderate improvement in metabolic control on magnesium and lipid concentrations in patients with type 1 diabetes.

OBJECTIVE: To evaluate the effect of clinically obtainable improvements in metabolic control in patients with type 1 diabetes on biochemical cardiovascular risk factors. RESEARCH DESIGN AND METHODS: Blood and 24-h urinary samples were obtained from 49 patients with type 1 diabetes before and after a run-in period and after 3 months of intervention, with frequent adjustment of insulin dosage according to measured blood glucose concentrations. RESULTS: The intervention caused a mean insulin dosage increment of 10%, a 20% decrease in fasting plasma glucose concentration, a 10% decrease in albumin corrected serum fructosamine, and a somewhat lesser decrease in HbAlc.A 14% decrease in the renal excretion of magnesium (Mg) was observed, but without a change in average serum Mg concentration. Serum HDL cholesterol increased 4%, and serum triglycerides decreased 10% as an average. Looking at individual patients, the decrease in serum triglycerides correlated with both the change in serum total Mg concentration and with the increase in insulin dosage. Using the change in serum total Mg concentration and in insulin dosage as independent variables in a multiple regression analysis, the coefficient of correlation with the decrease in serum triglycerides was 0.52. CONCLUSIONS: Moderate but clinically obtainable improvement of metabolic control in patients with type 1 diabetes seems to reduce the loss of Mg, increase serum HDL cholesterol, and decrease serum triglycerides. The decrease in serum triglycerides was associated with the change in serum total Mg concentration. These reductions in Mg loss and serum triglycerides might reduce the risk of developing cardiovascular disease in patients with type 1 diabetes.

Adolescent↗

PubMed1998

Methodological aspects of measuring human skeletal muscle electrolyte content and ouabain binding capacity.

The aim of the study was to evaluate the use of freeze-dried and dissected small muscle biopsy specimens ("dry") for the determination of human muscle electrolyte content and ouabain binding capacity, compared with an easier method, without this freeze-drying step ("wet"). Freeze-drying and dissection of muscle biopsy specimens reduced the variation in the determination of muscle potassium and magnesium content. The total coefficient of variation was 8.6% in the dry determination of muscle potassium content and 13.5% in the wet determination (P < 0.05). In the determination of muscle magnesium content, the total coefficient of variation was 7.4% in the dry determination and 13.7% when determined wet (P < 0.005). Muscle sodium content had a very large coefficient of variation, independent of the method used. The content of dry solids was too high in biopsies which were incubated in Tris-vanadate buffer (31.9%), compared to biopsies which were not incubated in Tris-vanadate buffer (24.9%, P < 0.001). Hereby, the measured ouabain binding capacity became too high when measured wet. In conclusion, muscle electrolyte content and ouabain binding capacity should be determined after drying and microdissection of the biopsies, because this method confers the least variation and the highest accuracy.

Aged↗

PubMed1998

Multiple anomalies, hypokalaemic paralysis and partial symptomatic relief by terbutaline.

In this paper a follow-up is presented of a case report initially described by Andersen in 1971. The patient presented with a syndrome including elements of familial periodic paralysis with hypokalaemia, long QT syndrome, ventricular ectopy, myopathy with fibre-type disproportion and dysmorphic features resembling Treacher Collins' syndrome. The main symptom was hypokalaemic paralysis. The episodes were accompanied by a lowered intracellular potassium content and an increase in intracellular sodium. Treatment with terbutaline, a Na/K-ATPase-stimulating drug, resulted in attack-free periods of approximately 9 months, after which the attacks reoccurred. The patient suffered severe attacks whenever treatment with terbutaline was stopped. The patient experienced two attacks of respiratory arrest, the second being fatal.

Abnormalities, Multiple↗

PubMed1996

[Bartter's syndrome. A condition with chronic hypokalemia].

Bartter's syndrome (BS) is a disease with severe hypokalaemia due to renal potassium wasting. The potassium loss is due to lesions at different sites within the renale tubule. Additional features include metabolic alkalosis, excess renal production of prostaglandins, hyperreninaemia, hyperaldosteronism and impaired pressor responses to exogenous angiotensin II. These secondary features are the result of renal potassium wasting. Symptoms are due to potassium deficiency, but many adult patients feel well despite marked hypokalaemia. The hypocalciuric variant of BS is called Gitelman's syndrome. These patients have a more benign course. The diagnosis of BS is one of exclusion, mainly of surreptitious vomiting, diuretic or laxative abuse. The primary treatment is potassium supplementation often in combination with potassium-sparing diuretics, prostaglandin inhibitors or ACE-inhibitors. With coexisting magnesium deficiency, magnesium supplementation might be effective.

Adult↗

PubMed1995

Biological variation of serum and urinary magnesium in apparently healthy males.

The biological variations of serum (S-) magnesium and urinary (U-) magnesium concentrations and excretions have been investigated. Serum samples, 24-h and fasting urinary samples were collected from each of 60 supposedly healthy male volunteers. In addition, 12 volunteers collected additional samples 7 and 112 days after the initial sample. The reference interval for S-magnesium was 0.765-0.997 mmol l-1. The biological variation for S-magnesium was 3.2% within subjects and 7.4% between subjects. This indicated an index of indivduality of 0.5, which means that significant changes in S-magnesium can occur within the limits of the reference interval, and that serial determinations of S-magnesium might prove useful as an indicator of changes in whole body magnesium status. It is, on the other hand, unlikely that a single determination of S-magnesium can be used in assessing whole-body magnesium status in the individual. The reference interval for the 24-h U-magnesium excretion, corrected for surface area, was 1.306-4.762 mumol min-1 1.73 m-2. The 24-h U-magnesium excretion exhibited a biological within-subject variation of 36% and a between-subject variation of 26%. The 24-h U-magnesium excretion did not correlate with S-magnesium, and only slightly (r = 0.58) with the fasting U-magnesium/creatinine concentration. This, and the very large coefficients of variation, make it unlikely that the renal magnesium excretion can be used as a measure of whole body magnesium status, or that changes in the renal magnesium excretion can be used as a measure of changes in whole body magnesium status.

Adult↗