Physical stress as a model to study variations in ADAMTS-13 activity, von Willebrand factor level and platelet activation.
Explore the source record for details and available documents.
ADAM Proteins↗
Biomedical subjects
T Hilberg
Publications and source records attributed to T Hilberg.
Physical training increases isometric muscular strength and proprioceptive performance in haemophilic subjects.
Sufficient muscular strength and proprioception lessen the risk of joint damage, however, both are impaired in haemophilic subjects. The aim of the study was to investigate proprioceptive performance and isometric muscular strength before and after a specialized training in haemophilic subjects (H) compared with two groups of control subjects (C). Nine subjects with severe haemophilia A, and eight 'active' C (AC) without haemophilia took part in a physical training programme over a 6-month period. Eleven 'passive' C (PC) were requested to avoid any additional training during this period. Proprioceptive performance and isometric strength were determined before and after the training programme. The maximal isometric muscular strength in the legs, bilaterally measured by knee extensor (and leg press) was increased (P < 0.05) by 34% (29%) after training in the H and by 20% (28%) in the AC groups while remaining unchanged in the PC group. The performance in one-leg-stand tests after training was increased (P < 0.05) in the H and AC groups. An improvement of angle reproduction of 20 degrees and 40 degrees (P < 0.05) in the H compared with the PC groups was seen in the tests. Quantitative sensory testing by the tuning fork showed an increase (P < 0.05) in performance of both H and AC groups. The results of the present study confirm that specific sports therapy focused on proprioceptive function and accompanied by gentle strength training with low resistance and 20-25 repetitions is able to increase proprioceptive performance and muscular strength with a minimal stress to the joints. It is strongly recommended that specialized sports therapy be included as an integral component of the complete treatment regimen of haemophilic subjects.
Adolescent↗
Thrombin potential and thrombin generation after exhaustive exercise.
Exhaustive exercise leads to an activation of blood coagulation, but the implications of this activation are still unclear. The aim of this study was to investigate if a hypercoagulant stage exists after exhaustive treadmill- or cycle exercise; intrinsic and extrinsic endogenous thrombin potential (ETP) were measured by using the method of Hemker et al. Thirteen healthy male subjects underwent an exhaustive treadmill (TR) or cycle (CY) ergometer test and a control-day in random order. Blood samples were taken, repeatedly, after a 30 min rest, immediately before and after, and 1 h after exercise for measuring intrinsic and extrinsic total thrombin potential (TTPin, TTPex) (including free and alpha 2 -macroglobulin-bound thrombin) and endogenous thrombin potential (ETPin, ETPex), aPTT, PT, F1 + 2 and TAT. In comparison to the pre-value taken immediately before the exercise, the intrinsic TTP was significantly (p < 0.05) increased directly after exercise (TR-TTPin, + 11.6 %; CY-TTPin, + 11.5 %). In contrast, ETPin remained unchanged after both exercises. Additionally for TTPex and ETPex, no changes after exercise were detectable. aPTT was significantly (p < 0.05) shorter after exercise (TR-aPTT, - 16.2 %; CY-aPTT - 17.5 %), F1 + 2-concentrations were higher (p < 0.05) (TR-F1 + 2, + 21.2 %; CY-F1 + 2, + 9.8 %), but TAT remained unchanged. Differences between TR or CY could not be determined. These results show the expected shortening of aPTT and the increase of F1 + 2 indicating an activation of the coagulation system during exercise. However, the unchanged intrinsic and extrinsic ETP lead to the conclusion that in healthy young male subjects the potential for thrombin generation is insignificant, is directly counterbalanced by alpha 2-macroglobulin and is independent of the type of exhaustive exercise done.
Adult↗
Drug-related deaths in a department of internal medicine.
BACKGROUND: Drug therapy is associated with adverse effects, and fatal adverse drug events (ADEs) have become major hospital problems. Our study assesses the incidence of fatal ADEs in a major medical department and identifies possible patient characteristics signifying fatal ADE risk. METHODS: During a 2-year period, a multidisciplinary study group examined all 732 patients who died--5.2% of the 13992 patients admitted to the Department of Internal Medicine, Central Hospital of Akershus, Nordbyhagen, Norway. Decisions about the presence or absence of fatal ADEs were based on aggregated clinical records, autopsy results, and findings from premortem and postmortem drug analyses. RESULTS: In 18.2% of the patients (133/732) (95% confidence interval, 15.4%-21.0%), deaths were classified as being directly (64 [48.1%] of 133) or indirectly (69 [51.9%] of 133) associated with 1 or more drugs (this equals 9.5 deaths per 1000 hospitalized patients). Those with fatal ADEs (cases) were older, had more diseases, and used more drugs than those without fatal ADEs (noncases). In 75 of the 133 patients with fatal ADEs, autopsy findings and/or drug analysis data were decisive for recognizing the ADEs; in 62 of the remaining 595 patients, similar data proved necessary to exclude the suspicion of a fatal ADE. Major culprit drugs were cardiovascular, antithrombotic, and sympathomimetic agents. CONCLUSIONS: Fatal ADEs represent a major hospital problem, especially in elderly patients with multiple diseases. A higher number of drugs administered was associated with a higher frequency of fatal ADEs, but whether a high number of drugs is an independent risk factor for fatal ADEs is unsettled. Autopsy results and the findings of premortem and postmortem drug analyses were important for recognizing and excluding suspected fatal ADEs.
Adolescent↗
Proprioception and isometric muscular strength in haemophilic subjects.
Haemophilia is characterized by intra-articular bleeding, often requiring immobilization, which may result in muscle atrophy and impaired proprioception. The aim of the study was to investigate differences in proprioceptive performance and isometric muscular strength of the lower limbs in haemophilic subjects compared with control subjects. Twelve subjects with severe haemophilia (11 haemophilia A; one haemophilia B) vs. 12 control subjects were matched for anthropometric data and tested for differences of proprioception (one-leg-stand, posturomed, angle-reproduction, and tuning fork tests) and isometric strength (leg press, knee extensor). The static proprioceptive performance of the haemophilic group, as measured by the one-leg-stand test (on hard or soft ground, with open or closed eyes; P < 0.05) was demonstrably impaired (by 41-363%). In contrast, the dynamic proprioceptive performance measured by the posturomed test did not show any difference between the groups. The local proprioceptive performance (angle-reproduction test) of the knee, (the most commonly affected joint in haemophiliacs) showed a trend to impaired function but was not distinctly different from that of controls. The quantitative sensory function (tuning fork) showed significant (P < 0.05) impairment of 9-10% in the haemophilic subjects. Additionally, the isometric muscular strength of the leg extensor was weaker (32-38%) in the haemophilic group when the limbs were tested individually as well as bilaterally (P < 0.05). In conclusion, the results suggest that global proprioceptive performance is impaired and that the isometric strength of the leg extensors is weaker in the haemophilic subjects. Therefore, specialized training for global proprioception would be helpful in order to compensate for proprioceptive deficits. This exercise regimen should also include safe strength-training for an optimal stabilization of the joints, but must be adapted to the individual needs and situations of the haemophilic subjects.p
Hemophilia A↗
Fatal adverse drug events: the paradox of drug treatment.
OBJECTIVE: Study patient characteristics, morbidity patterns and drug regimens associated with fatal adverse drug events (FADEs) amongst medical department inpatients. DESIGN: An observational, descriptive study using aggregated medical records, autopsies and pre and postmortem drug analyses. SETTING: A department of internal medicine at a Norwegian county hospital. SUBJECTS: All patients dying in the department over a 2-year period. RESULTS: The incidence of FADEs were 18.2% (133/732). Compared with non-FADE cases, FADE cases were older, used more drugs both on admission and at death, and had higher comorbidity (P < 0.001). Drugs suspected to cause or contribute to fatal outcome were mainly those used for treating chronic pulmonary diseases (terbutaline, theophylline), antithrombotic drugs (aspirin, warfarin, heparines) and drugs for treating coronary heart disease and heart failure (e.g. diuretics, nitrates, angiotensin converting enzymes (ACE) inhibitors, calcium channel blockers). Bronchodilatory drugs, antithrombotic drugs and cardiovascular drugs account for 26, 31 and 30 FADE cases, respectively. Patients dying from gastrointestinal diseases had the highest relative FADE occurrence (42%), cancer patients the lowest occurrence (4%). Serious drug-drug and drug-disease interactions were frequently suspected. Various degrees of inappropriateness in choice of drug, dosage or administration route were seen in 50% of FADE cases. CONCLUSIONS: This study shows a high incidence of FADEs associated with high age, high comorbidity and polypharmacy, and partly to inappropriate drug prescribing or use. Treatments frequently associated with FADEs were bronchodilatory treatment of patients with both chronic obstructive lung disease and coronary heart disease, vasodilatory treatment in patient with endstage heart failure and the combination of several antithrombotic drugs. A systematic strategy is needed to avoid unnecessary adverse drug events (ADEs).
Adult↗
Fatal overdose of zopiclone in an elderly woman with bronchogenic carcinoma.
The death of a 72-year-old woman with respiratory debilitation due to bronchogenic carcinoma is described. She overdosed herself with probably 200 to 350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood, was found to be 1.9 mg/L (4.8 micromol/L). This level is higher than many other zopiclone fatalities reported. We report a case where only zopiclone was detected.
Aged↗
Changes in blood coagulation and fibrinolysis associated with maximal exercise and physical conditioning in women taking low dose oral contraceptives.
Blood coagulation parameters (thromboplastin time. PT; activated partial thromboplastin time, aPTT; fibrinogen; antithrombin III, ATIII; von Willebrand factor-concentration, vWF; factor VIII-activity, FVIII) and fibrinolytic parameters (plasminogen; (alpha-antiplasmin; euglobulin-lysis-time, Elt; tissue plasminogenactivator-antigen, tPA-antigen; plasminogenactivator-1-antigen, PAI-1-antigen) were evaluated in 34 women on low-dose oral contraceptives (OC) twice at intervals of 12 weeks each time before and after maximal exercise. During the 12 weeks, 24 women took part in an aerobic conditioning program and 10 women were requested to avoid any kind of sports activity for this period. Blood samples were taken before training and before and after maximal treadmill exercise. This procedure was repeated after the training program. After maximal exercise we found a significant reduction of aPTT and PT (increase in %), a decrease in ATIII, vWF, fibrinogen, plasminogen and alpha2-antiplasmin but an increase in fibrinolytic activity (all p<0.05). Maximal exercise is associated with an increase in blood coagulation and fibrinolysis also in women taking OC. After the physical conditioning program an increase in fibrinolytic activity at rest was noted in the training group. Opposed to that the fibrinolytic activity at rest decreased in the control group after abstinence of sports activity over this period (p<0.05, MANOVA).
Adult↗
[Serotonergic syndrome. Serotonergic syndrome caused by paroxetine].
Explore the source record for details and available documents.
Antidepressive Agents, Second-Generation↗
Fatal combined intoxication with new antidepressants. Human cases and an experimental study of postmortem moclobemide redistribution.
Three cases are presented in which death was caused by suicidal intoxication with moclobemide in combination with a selective serotonin reuptake inhibitor. Both antidepressant drug types are considered to be relatively safe with regard to lethal overdose. However, the combination may cause the serotonin syndrome, a condition with a high mortality rate. In one of the cases, there was clinical information consistent with the serotonin syndrome, in the two other cases, there was no information of the clinical course. Postmortem redistribution of the selective monoamine oxidase inhibitor moclobemide was investigated in a rat model. Postmortem concentrations in blood from the vena cava and the heart were found to be in good accordance with antemortem concentrations. Postmortem concentrations in vitreous humour and various tissues were also measured. The apparent volume of distribution was calculated to be 0.95 +/- 0.10 l/kg, which is in the same range as that reported in man.
Adult↗
Clinical sciences and orthopaedics: case report homozygous APC resistance in an elite athlete.
We report the case of a 31 year old female elite athlete. During a routine check-up including a search for hereditary hemostatic risk factors for thrombosis, resistance to activated protein C was detected. Molecular analysis of the factor V gene revealed homozygosity for the factor V Leiden mutation. This is the first documented case of an elite athlete who is a homozygous carrier of factor V Leiden. Elite athletes may be exposed to several circumstantial thrombogenic risk factors and, therefore, special preventive measures in carriers of a congenital risk factor such as APC resistance are indicated. Essential measures are early anticoagulation during periods of immobilisation e.g. after sports-related injuries, a single dose of low-molecular-weight heparin specially for individuals with several thrombotic risk factors and/or leg muscle exercises for long-distance (air) travels and avoiding haemoconcentration with a sufficient oral fluid intake.
Activated Protein C Resistance↗
The extent of postmortem drug redistribution in a rat model.
The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.
Animals↗
Postmortem drug redistribution--human cases related to results in experimental animals.
Femoral blood is widely accepted as the most reliable postmortem specimen for drug analysis in forensic toxicology. There is considerable evidence that the drug concentrations in peripheral blood samples are closer to the antemortem level than the concentration in cardiac blood. In the present study drug concentrations measured in postmortem femoral and/or heart blood samples from eight cases were compared with the concentration found in serum samples from the same subject collected antemortem or perimortem. The drugs involved were amitriptyline, nortriptyline, imipramine, verapamil and chloroquine. Two additional cases with very early postmortem blood samples, as well as femoral blood samples from later autopsy, involved amphetamine and tetrahydrocannabinol. The results from the human cases were compared with results from rat experiments on similar drugs. The samples were analyzed by high performance liquid or gas chromatography. The cases with tricyclic antidepressants had a median postmortern femoral blood to antemortem serum drug concentration ratio of 3.3, the 95% reference range being from 1.1 to 6.0 (pooled data). Large variations of the ratios were seen. The extremes noted were a postmortem femoral blood to antemortem serum drug concentration ratio of 0.9 in a case with nortriptyline and 49 in the case with chloroquine. The low ratio in the former case could be due to attempted resuscitation, while the high ratio in the latter case is probably due to the extremely high apparent volume of distribution and a high blood to plasma concentration ratio for chloroquine. Accordingly, it is dubious whether the drug concentration found in femoral blood at autopsy can be accepted as being representative for the antemortem level. The results obtained from the human cases in the present study were generally in reasonable agreement with previous rat experiments, confirming that the animal studies when interpreted carefully, are indicative of the changes observed in man as well as a previous study in pigs. Studies on drug concentrations in pigs are not necessarily more representative for the findings in humans than experiments with a smaller animal like the rat. The postmortem concentration changes observed for tetrahydrocannabinol in man were found to be unpredictable, while in the accompanying experimental rat study there was a significant postmortem decrease in the tetrahydrocannabinol blood concentration measured in blood from the inferior vena cava. In special cases where the diagnosis of overdose is to be used as judicial evidence, a single sample of blood may prove insufficient. In such cases, analyses of several samples of blood and tissue will increase the possibility of reaching a correct conclusion, but reference values on drug concentrations in tissues are often missing.
Adolescent↗
APC resistance in an elite female athlete.
In a routine checkup the family history of an elite female mogul skier was found to contain an unusually high number of thrombotic incidents. This prompted us to do diagnostic thrombophilia studies, which revealed a resistance to activated protein C, a heterozygous factor V Leiden disorder. This is the first documented case of APC resistance in an elite female athlete. Since high performance sports are known to carry an increased risk of thrombogenesis, measures to avoid thrombosis or a thromboembolic event must be initiated in case of known APC resistance. Suitable measures are early anticoagulation during periods of immobilization, a single dose of low molecular weight heparin, leg muscle exercises for long distance flights, and avoidance of hemoconcentration with a sufficient oral fluid intake.
Adult↗
Postmortem amitriptyline pharmacokinetics in pigs after oral and intravenous routes of administration.
In this study we have evaluated the postmortem pharmacokinetics of amitriptyline (Ami) and metabolites in pigs after oral and intravenous administration, and the results are compared with previous studies in rats and humans. In addition a meticulous investigation of blood and tissue concentrations after postmortem intravenous infusion of Ami was undertaken. Of a total of 9 over-night fasted pigs, 3 were given 25 mg/Kg Ami orally, and another 3 pigs received an intravenous infusion lasting 1 h of 3.3 mg/Kg Ami prior to death. The final 3 pigs were sacrificed and then given the intravenous infusion after death. After approximately 5 h at room temperature, all carcasses were subsequently stored at 4-5 degrees C. Postmortem blood samples were collected at 0.25, 1, 2, 4, 8, 24, 48, and 96 h through an indwelling intracardial needle. Postmortem examination with blood and tissue sampling was performed 96 h after death. Analysis was carried out by high performance liquid chromatography with ultraviolet detection. Postmortem blood samples from the heart of the orally dosed animals revealed large and variable concentration increases of 99(30-243)% for Ami and 96(52-429)% for the main metabolite 10-OH-Ami at 96 h. In the intravenously infused live pigs heart blood Ami increased by 55(33-69)% and 10-OH-Ami increased by 232(76-240)%. Blood from the atria had significantly higher Ami concentrations than blood from both ventricles in the animals dosed while alive, and the drug concentration in femoral blood was higher than in heart blood (p < 0.01). In the orally dosed pigs the left lobe of the liver had significantly higher Ami levels than the right lobe. Tissue/blood Ami concentration ratios were generally lower than previously reported in rats and approximating the levels reported in humans. The animals infused intravenously after death demonstrated high drug levels in blood samples from central vessels, heart, lungs as well as cerebrospinal fluid and vitreous humour. This implies that the presence of a lethal concentration of a drug in just one sample of heart blood can prove worthless in a case where agonal drug infusion may have occurred.
Administration, Oral↗
[Drugs as a cause of death. A prospective quality assurance project in a department of medicine].
This study is part of a prospective quality assurance project in a Norwegian county hospital. The major aims of the study were to estimate the number of drug-related deaths; assess whether these were recognized by the clinicians, and (if not) discuss why the clinicians had difficulties in recognizing drug-related deaths. A panel of two internists, one pathologist, one pharmacologist and one pharmacist evaluated all inpatients deaths over a six-month period. Among 3,082 hospitalized patients, 169 died. Of these deaths, 20 were classified as probably (nine) or possibility (11) drug-related. Only two of the deaths were recognized as such by the clinicians in the ward. The reasons for the clinicians failure to recognize adverse drug reactions include frequent presence of multiple diseases, polypharmacy and inadequate guidelines on how to look for adverse reactions to drugs. A two-year survey aimed at studying these aspects in depth is in progress.
Adrenergic beta-Agonists↗
[Frequency, reporting and classification of drug-related deaths].
In order to reach an estimate of drug-related deaths, the Adverse Drug Reaction Committee/the Norwegian Medicines Control Authority obtained access to data from the Department of Internal Medicine in a Norwegian county hospital. The criteria for classifying possible/probable cause of drug-related deaths were assessed. 6.5 deaths per 1,000 hospitalized persons were found to be probably or possibly drug-related. This figure far exceeds the numbers reported in the literature (0.9-4.4 per 1,000 hospitalized). Only two cases were detected by the clinician, one of which was reported to the Adverse Drug Reaction Committee via the spontaneous reporting system. The current criteria for assessing drug-related causes of death appear to be inadequate.
Adult↗
Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution.
An experimental rat model was used to study postmortem redistribution of amitriptyline (AMI). Two hours after a subcutaneous injection with 20 mg of amitriptyline, the rats (n = 40) were anaesthetized and blood samples were drawn from the femoral vein and the heart. The rats were then sacrificed by CO2 and left at room temperature for either 0.1, 1, 2, 5, 24, 48, or 96 h. Postmortem blood samples from the heart and the inferior vena cava, and tissue samples from the lungs, heart, liver, right kidney, thigh muscle, the wall of the abdominal vena cava and brain were analyzed by high performance liquid chromatography. A significant increase was observed within 2 h postmortem in heart blood and later also in blood from the inferior vena cava. At 96 h postmortem the concentration increase was 4.4 +/- 0.5-fold (P < 0.01) and 3.0 +/- 1.1-fold (P < 0.05) as compared to the antemortem values observed in heart blood and blood from the inferior vena cava, respectively (mean +/- SEM). In the lungs there was a fall in the concentration of AMI from 148 +/- 16.7 mumol/kg at 0.1 h to 49.1 +/- 7.8 mumol/kg at 96 h postmortem (P < 0.01). In the vessel wall of the abdominal vena cava there was also a significant fall in drug concentration, while in heart muscle and liver an increase in drug concentration was observed. In animals where the lungs were removed agonally (n = 7), the drug concentration in heart blood had increased significantly less at 2 h postmortem.(ABSTRACT TRUNCATED AT 250 WORDS)
Amitriptyline↗