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Biomedical subjects

L Knudsen

Publications and source records attributed to L Knudsen.

At least 19 recordsLinked to original sources

Bedside coagulometry during intravenous heparin therapy after coronary angioplasty.

UNLABELLED: In order to assess the applicability of a bedside coagulometer for measurement of b-APTT, serial blood samples were obtained from 20 patients receiving intravenous heparin treatment following PTCA, and from 5 healthy volunteers. B-APTT was analysed bedside on the Hemochron coagulometer; p-APTT and p-heparin, measured as factor anti-Xa activity, were analysed ex-vivo in the laboratory. B-APTT values, determined by the Hemochron coagulometer, were closely correlated to p-heparin (r=0.83, p<0.001, SD=52 seconds (sec), n=89), and duplicate determinations of b-APTT on the Hemochron coagulometer showed an acceptable repeatability. However, an APTT ratio of 1.5-2.5 was not related to a therapeutic p-heparin level, neither as measured by the Hemochron device nor in the laboratory. BACKGROUND: When administering intravenous heparin during angioplasty procedures, a quick and reliable method for safe and effective monitoring of anticoagulation is necessary. OBJECTIVE: To assess the applicability of a bedside coagulometer, measuring the activated partial thromboplastin time (APTT) in patients receiving intravenous heparin treatment after percutaneous transluminal coronary angioplasty (PTCA). METHODS: In patients with stable angina pectoris, receiving intravenous heparin treatment following PTCA, serial blood samples were obtained by venipuncture and from the arterial sheath for analysis of whole blood APTT (b-APTT), and plasma heparin concentration (p-heparin). Additionally, in healthy volunteers blood samples were obtained after a single bolus injection of heparin. B-APTT was analysed bedside on the Hemochron coagulometer; p-APTT and p-heparin, measured as factor anti-Xa activity, were analysed ex-vivo in the laboratory using conventional analytical methods. RESULTS: In 20 patients a total of 94 venous and 69 arterial blood samples were analysed, and in five healthy volunteers analyses were performed in 20 venous blood samples. B-APTT values, determined by the Hemochron coagulometer, were closely correlated to p-heparin (r=0.83, p<0.001, SD=52 seconds (sec), n=89). An APTT ratio of 1.5-2.5 was not related to a therapeutic p-heparin level, however, neither when using APTT assessed by the Hemochron device nor APTT measured in the laboratory. Duplicate determinations of b-APTT on the Hemochron coagulometer showed an acceptable repeatability; the mean difference between duplicate measurements was 4 sec (coefficient of variation (c.v.)=6%, p<0.05, n=163). CONCLUSIONS: In patients receiving intravenous heparin after PTCA treatment, b-APTT values measured by the Hemochron method showed an acceptable repeatability and were significantly correlated to p-heparin.

Adult↗

[Self management of peroral anticoagulant therapy in patients with artificial heart valves].

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.

Adult↗

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health.

The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Biomarkers, Tumor↗

[Atraucan, a new needle for spinal analgesia].

One hundred and six consecutive patients, aged below 40 years, scheduled for surgery in the lower part of the body were chosen for this study. Patients were allocated randomly to have spinal analgesia with either a Sprotte 24G or an Atraucan 26G spinal needle. Incidences of insufficient blocks were higher after dural puncture with the Atraucan needle. Nineteen patients reported post dural puncture headache (PDPH) with a significantly higher proportion in the Atraucan group (two patients suffered mild (4%) and 14 severe (98%) PDPH) compared to the Sprotte group (three patients suffered mild (6%) PDPH. Eight patients (16%), all in the Atraucan group, required an epidural blood patch. Ease of needle insertion and number of puncture attempts were the same for both needles. We conclude that due to the high incidence of PDPH the Atraucan 26G spinal needle cannot be recommended for spinal analgesia in young patients.

Adult↗

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs.

It has not previously been clear whether cytogenetic biomarkers in healthy subjects will predict cancer. Earlier analyses of a Nordic and an Italian cohort indicated predictivity for chromosomal aberrations (CAS) but not for sister chromatid exchanges (SCES). A pooled analysis of the updated cohorts, forming a joint study base of 5271 subjects, will now be performed, allowing a more solid evaluation. The importance of potential effect modifiers, such as gender, age at testing, and time since testing, will be evaluated using Poisson regression models. Two other potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Biomarkers↗

Levels of prothrombin activation peptide F1+2 in patients with a bleeding tendency.

Numerous recent publications point to significant improvements in haemostasis in the bleeding patient suffering from haemophilia with inhibitors when a recombinant activated factor VII (rFVIIa) molecule is administered in high doses. In theory, activated factor VII (FVIIa) is believed to initiate haemostasis through its physiological interaction with tissue factor at sites of cellular injury, whereby factor X (FX) activation and, in consequence, thrombin formation is amplified. There has been speculation, however, whether high circulating FVII procoagulant (FVII:C) levels may induce systemic coagulation activation. The present retrospective investigation was undertaken to study, ex vivo, the influence of treatment with rFVIIa as assessed by the sensitive marker of prothrombin conversion, prothrombin fragment F1+2, in plasma samples. Study subjects consisted of: seven people suffering from thrombocytopenia participating in a study of the influence of rFVIIa on the bleeding time, in whom serial plasma samples had been collected before and subsequently at 10, 60 and 180 min after infusion of rFVIIa; four haemophilia A patients with inhibitors to FVIII undergoing surgery; two haemophilia A patients with inhibitors treated with rFVIIa for minor bleedings on 16 occasions in whom plasma samples had been collected before and 10-15 min after rFVIIa infusion; and two FVII-deficient patients undergoing treatment with rFVIIa. A group of seven haemophilia A patients with no signs of inhibitors subjected to a pharmacokinetic study of a plasma-derived FVIII concentrate served as controls. In the group of thrombocytopenic patients our results showed a mean increase in F1+2 following doses of 50 microg/kg body weight and 100 microg/kg body weight of rFVIIa of 1.1 and 1.4 nmol/l, respectively, with a gradual increase over time, but there was no significant correlation between FVII:C and the corresponding values of F1+2. During and after haemophilic inhibitor surgery, a mean increase in F1+2 of 1.44 nmol/l (range 0.6-3.2 nmol/l) was found, whereas 16 matched samples collected during treatment for minor bleedings showed a mean increase in F1+2 of 0.10 nmol/l (range -0.12 to 0.20 nmol/l). In FVII-deficient individuals, the mean rise in F1+2 was <0.10 nmol/l. In the control group, the mean elevation of F1+2 was 0.13 nmol/l (range -0.5 to 0.7 nmol/l). Hence, our results show that only discrete changes in F1+2 follow administration of rFVIIa.

Adult↗

[Total parathyroidectomy and autotransplantation of parathyroid tissue. Functional assessment of the autograft 5-10 years after surgery with the help of local ischemic blockade].

The aim of the present study was to assess the long-term function of autotransplanted parathyroid tissue. From the medical records of a consecutive series of 21 patients we found that during the time of follow-up (79 months) one patient developed parathyroid graft dependent recurrent hyperparathyroidism (HPT) and one patient suffered from hypoparathyroidism. Nine of the patients were available for measurements of the plasma concentrations of intact parathyroid hormone (iPTH) at rest and during a shortlasting ischaemic blockade of the autotransplant. In eight patients, the ischaemic blockade reduced the concentration of iPTH with on average 62% as compared to baseline values. In one patient, the autotransplant had been resected and as expected, iPTH did not change during ischaemic blockade. Our results indicate that total parathyroidectomy with autotransplantation provides a rational alternative to the surgical treatment of secondary HPT and that the ischaemic blockade manoeuvre seems suitable for assessment of the function of parathyroid autotransplants.

Adult↗

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.

Administration, Oral↗

Clinical evaluation of Duraflo II heparin treated extracorporeal circulation circuits (2nd version). The European Working Group on heparin coated extracorporeal circulation circuits.

OBJECTIVES: To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out. METHODS: In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II). RESULTS: Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (> 24 h) was significantly lower when they received heparin treated circuits versus controls. CONCLUSION: These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.

Adult↗

Self management of oral anticoagulant therapy after heart valve replacement.

OBJECTIVE: Patients with mechanical heart valves require lifelong oral anticoagulant treatment which entails frequent blood sampling and dosage adjustment. The purpose of this study was to investigate the feasibility of letting heart valve operated patients manage blood specimen analysis and dosage adjustment themselves. METHODS: A total of 21 patients were enrolled in the study and followed for at least 9 months postoperatively. Immediately after the heart valve operation they were trained in operating a CoaguChek international normal ratio (INR) monitor to analyze capillary whole blood samples. Subsequently training in dosage adjustment was accomplished and all patients were considered fully capable of self management after 30 weeks. In the training period, parallel laboratory INR measurements were made at 3-4 week intervals for reference. A control group of 20 patients was matched, respectively, to the study group. The INR target range was 2.0-3.0. RESULTS: Out of the 21 study patients 19 continued self management beyond 9 months. The median INR value obtained with the monitor was within therapeutic target range for all study patients and only 15 out of 20 control patients were within this range. The mean systematic deviation between laboratory and CoaguChek INR was 7.8% but each patient had a constant characteristic deviation from -11 to +21%. The study patients were within therapeutic target range 77% of the time compared with 53% for the control patients. CONCLUSIONS: Self management of oral anticoagulation is feasible for selected patients and constitutes a significant service improvement compared with conventional management. The CoaguChek monitor seems sufficiently accurate and reliable for self testing and the treatment quality is comparable or even better than conventional management. Assessment of the rate of bleeding and thrombo-embolic events shall be settled in studies comprising larger number of patients.

Administration, Oral↗

Middle cerebral artery blood velocity during rowing.

Dynamic exercise increases the transcranial Doppler determined mean blood velocity in basal cerebral arteries corresponding to the cortical representation of the active limb(s) and independent of the concomitant rise in the mean arterial pressure. In 12 rowers we evaluated the middle cerebral artery blood velocity response to ergometer rowing when regulation of the cerebral perfusion is challenged by stroke synchronous fluctuation in arterial pressure. Rowing increased mean cerebral blood velocity (57 +/- 3 to 67 +/- 5 cm s-1; mean +/- SE) and mean arterial (86 +/- 6 to 97 +/- 6 mmHg) and central venous pressures (0 +/- 2 to 8 +/- 2 mmHg; P < 0.05). The force on the oar triggered an averaging procedure that demonstrated stroke synchronous sinusoidal oscillations in the cerebral velocity with a 12 +/- 2% amplitude upon the average exercise value. During the catch phase of the stroke, the mean velocity increased to a peak of 88 +/- 7 cm s-1 and it was in phase with the highest mean arterial pressure (125 +/- 14 mmHg), while the central venous pressure was highest after the stroke (20 +/- 3 mmHg). The results suggest that during rowing cerebral perfusion is influenced significantly by the rapid fluctuations in the perfusion pressure.

Adult↗

Evaluation of bactericidal activity and lag of regrowth (postantibiotic effect) of five antiseptics on nine bacterial pathogens.

Lag of regrowth or postantibiotic effect (PAE) relates to suppression of bacterial regrowth following short exposure to an antimicrobial agent. A delay in regrowth has not yet been studied for antiseptics to any great extent. We therefore examined and compared the lag of regrowth and the bactericidal activity of five antiseptics (chloramine T, chlorhexidine, povidone-iodine, phenoxyethanol and mandelic-lactic acid) against nine bacterial pathogens. Delay in regrowth was determined by application of two concentration-time schedules: a test concentration at the MBC with a contact time of 1 h or using fixed suboptimum concentration of each antiseptic for 2 min (optimum concentrations sterilized the culture, impeding assessment of regrowth) followed by a neutralization-dilution step and subsequent viable counting to follow bacterial regrowth. Each antiseptic displayed a different spectrum of activity in terms of MIC or MBC, bactericidal effect and lag of regrowth. The delay in regrowth varied from 0 to 5.7 h with only a few discrepancies between the two treatment schedules. Mandelic-lactic acid and chloramine T induced a significantly longer lag as compared with the other agents, whereas phenoxyethanol produced the shortest lag values. No significant correlation between the killing rate and the lag of regrowth could be demonstrated. Information on bactericidal activity, as well as lag of regrowth, could be a useful screening method for the efficacy of antiseptics. Moreover, data on lag of regrowth could contribute to the choice of antiseptic and guide in determining the optimum interval between repeated applications of antiseptics.

Anti-Infective Agents, Local↗

Monitoring thrombin generation with prothrombin fragment 1.2 assay during cardiopulmonary bypass surgery.

UNLABELLED: Despite high plasma levels of heparin during cardiopulmonary bypass surgery, activation of the coagulation system has been reported. We hypothesize that the coagulation system activity most appropriately could be assessed by molecular markers of thrombin generation. The aim of the present study was to describe the changes in thrombin generation during CPB, using prothrombin fragment F1 + 2 (F1.2) as an indicator and evaluate different blood sampling regimens for interpretation of the F1.2 measurements. Twenty patients, operated under extracorporeal circulation with coronary artery bypass grafting (CABG), comprised the study material. The heparin levels were maintained above 2.5 IU/ml throughout the bypass procedure and the functional AT-III level was kept above 0.5 U/ml. Despite of this anticipated inactivation of the coagulation system, the concentrations of F1.2 and FpA increased throughout CPB, particularly after release of the aortic crossclamp. F1.2 and FpA correlated significantly (R = 0.69). No statistically significant correlation was found between F1.2 formation rate and age, bodyweight, baseline ACT, ACT after 200 IU heparin/kg, average heparin concentration during CPB or average AT-III level during CPB. CONCLUSIONS: Thrombin formation seems to be a continuous process during CPB despite adequate heparinization. The pattern of thrombin generation can be assessed most appropriately in terms of F1.2 generation rate. Extraordinary high levels of F1.2 were seen after release of the aortic crossclamp, indicating that the periods before and after aortic crossclamping should be evaluated separately.

Adult↗

A study of cognitive functions in young Parkinsonian patients.

The purpose of the study was to evaluate the neuropsychological performance of younger Parkinson's disease (PD) patients compared to healthy controls. A group of young optimally treated PD patients younger than 56 years was pair-matched with a group of healthy controls for age, social class and the two WAIS subtests "vocabulary" and "similarities". As a group, the PD patients were satisfactory in verbal logical intelligence, but evaluation of neuropsychological tests showed difficulties in short memory span, constructional function and logical visual sequential cognition. Young PD patients have some cognitive impairment for which they are able to compensate for a time because of preserved intelligence. More attention should be paid to possible problems in their jobs and social life.

Adult↗

Five to 10 years follow-up after total parathyroidectomy and autotransplantation of parathyroid tissue: evaluation of parathyroid function by use of ischaemic blockade manoeuvre.

The aim of the present study was to assess the long-term function of autotransplanted parathyroid tissue in patients with chronic renal disease. We examined the medical records of a consecutive series of 21 patients with chronic renal failure, who had undergone total parathyroidectomy with autotransplantation. During the time of follow-up, on average 79 months, one patient developed graft-dependent recurrent hyperparathyroidism and one patient suffered from persistent hypoparathyroidism. Nine of the patients were available for a clinical study. In these patients we measured the plasma concentration of intact PTH in blood from the arm contralateral to the graft-bearing arm at rest and during a short-lasting ischaemic blockade of the graft site from the circulating blood. At rest all nine patients had parathyroid hormone (PTH) values within the normal range. The ischaemic blockade produced a marked reduction in the plasma concentration of intact PTH in eight of the patients indicating well functioning autografts. Prior to the examination the patient with recurrent hyperparathyroidism had undergone resection of the autograft. In this patient, ischaemia of the former graft site did not cause any change in the concentration of PTH indicating normally functioning residual parathyroid tissue in the neck. Thus, the ischaemic blockade manoeuvre seems suitable for the assessment of autografted parathyroid tissue. Our results indicate that total parathyroidectomy with autotransplantation provides a rational alternative to the surgical treatment of secondary hyperparathyroidism.

Adult↗

Regional differences exist in elastic wall properties in the ureter.

According to classical mechanical theory, the passive elastic properties of a distensible tube are important for the resistance to flow. The aim was to study luminal dimensions under pressure loading and the tension-strain distribution of the ureter in anaesthetized pigs by means of impedance planimetry. Stepwise inflation of an intraluminal balloon in which the cross-sectional area (CSA) and pressure were measured provided the distension stimulus in the ureteropelvine junction, in the midureter and in the intramural part of the ureter at the ureterovesical junction. The circumferential tension-strain distributions were computed from steady state values of these measurements. The CSA always reached equilibrium within the two-minute distension period. The steady state pressure-CSA curves were nonlinear and differed between the three measuring points (p < 0.001). The most pronounced difference was found between the ureteropelvine junction and the two other measuring points. At the lowest applied pressure of 1 kPa the steady state CSA was 15.4 +/- 1.1, 16.6 +/- 1.1, and 19.9 +/- 19.9 mm2 in the intramural part, middle part and ureteropelvine junction, respectively. At the maximum pressure the figures were 41.9 +/- 2.9, 47.0 +/- 2.7, and 73.1 +/- 8.2 mm2 for the three locations, respectively. The circumferential tension-strain distributions were nonlinear with an exponential-like behaviour. The tension-strain curve obtained from the ureteropelvine junction was translated to the right compared to the curves obtained from the two other measuring points (p < 0.05) indicating that the ureteropelvine junction was more compliant than the two other locations.

Analysis of Variance↗