Search PubMed⌕ Search

Biomedical subjects

L Knudsen

Publications and source records attributed to L Knudsen.

At least 19 recordsLinked to original sources
PubMed2006

Toll-like receptors mediate proliferation and survival of multiple myeloma cells.

Multiple myeloma (MM) is an incurable B-cell malignancy characterized by accumulation of malignant plasma cells in bone marrow (BM) and recurrent or persistent infections. Toll-like receptors (TLRs) are essential in the host defense against infections and today 10 human TLRs (TLR1-TLR10) and one TLR-homolog (RP105) have been characterized. B cells express several TLRs (mainly TLR1, 6, 7, 9, 10 and RP105) and TLR-initiated responses in B cells include proliferation, anti-apoptosis effect and plasma cell (PC) differentiation. The present study was designed to analyze the role of TLRs in MM. We show that frequent expressions of TLRs were detected in cell lines from MM patients (minimum six TLRs in each). In comparison, only few TLRs (mainly TLR1 and or RP105) were found expressed in PCs from BM of healthy donors. In addition, TLR-specific ligands induce increased proliferation and survival of the MM cell lines, partially due to an autocrine interleukin-6 production. Importantly, we demonstrate that also PC from MM patients proliferates in response to TLR-specific ligands. In conclusion, TLR-ligands may contribute to increased growth and survival of MM cells in MM patients.

Cell Line, Tumor↗
PubMed2005

Improvement of glucose tolerance in type 2 diabetic patients: traditional vs. modern insulin regimens (results from the Austrian Biaspart Study).

OBJECTIVE: Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet. The aim of the present study was to investigate whether meal-related (breakfast, lunch, dinner) application of biphasic insulin aspart 30 (BIAsp 30) provides better glycaemic control than administration of biphasic human insulin 30 (BHI 30) twice per day. RESEARCH DESIGN AND METHODS: In a multi-centre, randomized, open-label parallel trial, a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks. HbA1c and glycemic exposure parameters were measured at predefined intervals. RESULTS: The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08% (p = 0.6419). Analysing the 7-point blood-glucose (BG) profiles, significant differences in BG levels were observed after lunch (156 vs. 176 mg/dl, p = 0.0289), before dinner (142 vs. 166 mg/dl p = 0.006) and after dinner (154 vs. 182 mg/dl p = 0.002) in favour of BIAsp 30 insulin. Prandial BG increment was lower in the BIAsp 30 group at breakfast (p = 0.057) and lunch (p < 0.0005). No difference was found regarding safety parameters in the two treatment groups. CONCLUSIONS: This study demonstrates that meal-related BIAsp 30-insulin maintains postprandial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients.

Adult↗
PubMed2004

Treatment of a transdiaphragmatic fistula with an endobronchial-blocking catheter.

We report a case of a bronchosubphrenic fistula in a 59-year-old female following hemicolectomy complicated by fecal peritonitis. The patient needed intubation and positive-pressure ventilation, which caused a massive air leak. The fistula was treated using an endobronchial blocking catheter in combination with antibiotic treatment and drainage.

Abscess↗
PubMed2003

Retrospective exposure assessment and quality control in an international multi-centre case-control study.

The paper presents the exposure assessment method and quality control procedure used in an international, multi-centre case-control study within a joint Nordic and Italian cohort. This study was conducted to evaluate whether occupational exposure to carcinogens influenced the predictivity of high frequency of chromosomal aberrations (CA) in peripheral lymphocytes for increased cancer risk. Occupational hygienists assessed exposures in each participating country: Denmark, Finland, Italy, Norway and Sweden. The exposure status to a carcinogen or a clastogen was coded in the cohort according to the original CA studies at the time of CA testing, but not for the whole work life. An independent occupational hygienist coordinated harmonization of the assessment criteria and the quality control procedure. The reliability of the exposure assessments was calculated as deviation from the majority of the assessors, as Cohen's kappa and as overall proportion of the agreements. The reassessment of the exposures changed the exposure statuses significantly, when compared with the original cohort. Harmonization of the exposure criteria increased the conformity of the assessments. The prevalence of exposure was higher among the original assessors (the assessor from the same country as the subject) than the average prevalence assessed by the other four in the quality control round. The original assessors classified more job situations as exposed than the others. Several reasons for this are plausible: real country-specific differences, differences in information available to the home assessor and the others and misunderstandings or difficulties in translation of information. To ensure the consistency of exposure assessments in international retrospective case-control studies it is important to have a well-planned study protocol. Due to country-specific environments a hygienist from each participating country is necessary. A quality control study is recommended, to be performed as described, combined with round-table meetings to minimize information bias between the assessors.

Carcinogens↗
PubMed2001

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↗
PubMed1998

[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↗
PubMed1998

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↗
PubMed1998

[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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

[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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗