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Biomedical subjects

P D Jensen

Publications and source records attributed to P D Jensen.

At least 19 recordsLinked to original sources
PubMed2006

Individual and joint actions of selenate and methylmercury on the development and survival of insect detritivore Megaselia scalaris (Diptera: Phoridae).

Despite the important roles played by insects in most ecosystems, surprisingly little is known about how anthropogenic pollutants or their mixtures interact to affect insect populations. The independent and joint actions of selenate and methylmercury on a ubiquitous insect detritivore, Megaselia scalaris (Loew), were determined in this study. Ovipositing females did not distinguish between untreated food sources and those contaminated with toxic concentrations of selenate, methylmercury, or both chemicals in combination. Even at the highest concentrations of pollutants, no negative effects were observed for the egg stage. However, larval survival was significantly decreased and development significantly prolonged by selenate and methylmercury individually at low or intermediate ecologically relevant treatment levels. Potentiation was strongly evident because mixtures containing concentrations as little as only 1% of the respective individual median lethal tolerances (LC(50)s) caused significantly more mortality and delayed larval development than would be expected from the responses selenate and methylmercury elicit individually. However, survival and pupal development was not affected at any rate tested. Female fecundity was significantly decreased by methylmercury but not by selenate or mixture treatments. The relative toxicity to M. scalaris of each of the individual and joint treatments was selenate (LC(50) = 260 microg/g) < methylmercury (LC(50) = 22 microg/g) < the mixture at approximately 5% of the LC(50) concentration of each of the components (12 microg/g selenate plus 1.0 microg/g methylmercury). The increased mortality and delayed larval development within sites contaminated by selenate, methylmercury, or combination of the two have substantial implications for the ecology, population dynamics, and sustainability of M. scalaris populations. If these results can be extrapolated to other arthropod detritivores, ecosystem food-web function may be substantially affected.

Animals↗
PubMed2001

Indirect evidence for the potential ability of magnetic resonance imaging to evaluate the myocardial iron content in patients with transfusional iron overload.

The purpose of this study was to evaluate the potential ability of magnetic resonance imaging (MRI) for evaluation of myocardial iron deposits. The applied MRI technique has earlier been validated for quantitative determination of the liver iron concentration. The method involves cardiac gating and may, therefore, also be used for simultaneous evaluation of myocardial iron. The tissue signal intensities were measured from spin echo images and the myocardium/muscle signal intensity ratio was determined. The SI ratio was converted to tissue iron concentration values based on a modified calibration curve from the liver model. The crucial steps of the method were optimized; i.e. recognition and selection of the myocardial slice for analysis and positioning of the regions of interest (ROIs) within the myocardium and the skeletal muscle. This made the myocardial MRI measurements sufficiently reproducible. We applied this method in 41 multiply transfused patients. Our data demonstrate significant positive linear relationships between different iron store parameters and the MRI-derived myocardial iron concentration, which was significantly related to the serum ferritin concentration (rho=0.62, P<0.0001) and to the MRI-determined liver iron concentration (rho=0.36, P=0.02). The myocardial MRI iron concentrations demonstrated also a significant positive correlation with the number of blood units given (rho=0.45, P=0.005) and the aminotransferase serum concentration (rho=0.54, P=0.0008). Our data represents indirect evidence for the ability of MRI techniques based on myocardium/muscle signal intensity ratio measurements to evaluate myocardial iron overload.

Adolescent↗
PubMed2001

Expression of CD2 and activation markers on blood T-helper cell subsets in patients with transfusional iron overload.

The aim of the present study was to investigate the relationship between different measures of iron status, and the expression of CD2, and the activation markers CD25, CD71, CD45RO, HLADR CD38 within the Th-cell subset in patients with progressive transfusional iron overload. We estimated the expression of the activation surface markers on the Th cells of peripheral blood by flow cytometry from 22 multiply transfused patients. The number of CD2 binding sites (BS) on Th cells was significantly higher in the patients (82 917 +/- 30 801) than in age-matched normal controls (41 145 +/- 6989, P < 0.0001). When investigating whether this difference could be due to the iron overload we found the number of CD2 BS closely related to the iron saturation of serum transferrin (TfS) (R2 = 0.78, P < 0.001). The relationship to the serum ferritin concentration and to the number of blood units given was weaker, but also significant (R2 = 0.22, P < 0.027, respectively, R2 = 0.21, P < 0.032). Also the fraction of mature memory Th cells which express CD45RO at a high level was directly related to the TfS (R2 = 0.57, P < 0.0001), while the expression of CD38 within the Th cell fraction was inversely related to the TfS (R2 = - 0.43, P = 0.009). The expression of HLA-DR (but not of CD25 and CD71) was also directly related to the TfS (R2 = 0.29, P = 0.01). Our results show a clear, statistical relationship between the iron status and the expression of surface markers within Th cells in multiply transfused patients.

ADP-ribosyl Cyclase↗
PubMed1999

Relevance of in vitro leukaemia cell survival to short- and long term clinical outcome in AML.

In ninety-three cases of newly diagnosed acute myeloid leukaemia (AML) we investigated the importance to short- and long term clinical outcome of the in vitro short term leukaemia cell survival as measured by a 4-day MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)-assay. In 67 patients treated by intravenous remission induction therapy we found that patients who after the first induction cycle or after induction therapy overall achieved a complete remission (CR) had leukaemia cells with significantly lower in vitro cell survival ability than cells of non-responders (p = 0.02 and 0.06, respectively). These relations remained statistically significant in subsequent multivariate analyses. Likewise, a favourable effect of low in vitro leukaemia cell survival on overall survival of the patients was detected in the (largest) subgroup of adult patients treated uniformly by the same remission induction regimen as well as in all patients. However, in the 44 patients, who achieved CR, the in vitro leukaemia cell survival did not show significance to remission duration or time to first relapse. Furthermore, the leukaemia cell survival (MTT-assay) did not to correlate with the Bcl-2 expression level (quantitative flow cytometry) of the leukaemia cells (r = 0.18, n = 34, p = 0.32). In addition, in a cell line model employing the growth factor dependent MO7 human AML cell line, growth factor withdrawal was associated with rapid onset of cellular apoptosis as evaluated by morphology, occurrence of a subG1 peak in DNA histograms, and loss of cellular activity in the MTT-assay. In contrast, a more moderate decline in Bcl-2 expression and gradual loss of ability to exclude the trypan blue dye was seen in the leukaemia cells in response to growth factor withdrawal. We conclude, that the MTT-assay provides a simple and sensitive method for measuring in vitro cell survival. The differences in leukaemia cell survival seen in AML may well be clinically relevant and may help to provide a better understanding of clinical drug resistance.

Acute Disease↗
PubMed1998

[Quantification of iron level in the liver by MR imaging in patients treated for transfusion siderosis].

Patients with chronic blood transfusion requirements develop progressive iron overload, which is followed by organ damage in severe cases. Chemical determination of the liver iron concentration in liver biopsies is still regarded as the gold-standard for a precise determination of the degree of iron overload, but cannot be performed just for determination of the liver iron concentration alone due to the possible harmful side effects due to percutaneous liver biopsies. We have therefore validated a non-invasive MRI-technique based on the calculation of the ratio between the signal intensity (SIR) of the liver and skeletal muscle. We found a good correlation between the chemically determined liver iron concentration and the corresponding SIR-values (r2 = 0.98, p < 0.0001) low inter-day variation (2.9 +/- 2.7 mumol Fe/g) indicating that our non-invasive method is applicable for the determination of the liver iron concentration and may also be used for monitoring the efficacy of iron chelation by repeated measurements.

Biopsy↗
PubMed1997

Cardiac function during iron chelation therapy in adult non-thalassaemic patients with transfusional iron overload.

It is well-documented that iron chelation by desferrioxamine protects/improves the cardiac function in blood transfusion-dependent children suffering from beta-thalassaemia. In patients who do not become dependent upon blood transfusion until adulthood (ANT-patients), iron chelation by desferrioxamine may affect the cardiac function in unknown ways, presumably because age-related changes in the heart may cause iron chelation to affect the cardiac function in different ways. We therefore followed the left ventricular ejection fraction (LVEF) by multigated radionuclide angiography in 16 iron-loaded ANT-patients during iron chelation alone and after increasing the efficacy of chelation by vitamin C supplementation. During 12 months of iron chelation the mean LVEF fell significantly from 63.3% to 58.0% (p=0.04). Individual changes in LVEF did not correlate significantly with age but with the pretreatment liver iron concentration. After initiation of vitamin C supplementation, the mean LVEF increased from 55.9% to 65.3% (p=0.01). Our data suggest that in ANT-patients prolonged desferrioxamine treatment without vitamin C supplementation may be associated with reduced LVEF, whereas vitamin C supplementation seems to benefit the cardiac function. Similar findings have not been described in beta-thalassaemia and may hence be specific for ANT-patients. However, our findings have to be confirmed by controlled studies.

Adolescent↗
PubMed1996

The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload.

Long-term follow-up data are presented on changes in peripheral blood counts and Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron chelation treatment with desferrioxamine for up to 60 months. The erythroid marrow activity was indirectly evaluated by repeated determinations of the serum transferrin receptor concentration. The efficacy of iron chelation was evaluated by repeated quantitative determination of the liver iron concentration by magnetic resonance imaging. Reduction in the Hb requirement ( > or = 50%) was seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was highly effective showed improvement of erythropoietic output accompanied by an increase in the serum transferrin receptor concentration. It is concluded that reduction in cytopenia in MDS patients may be accomplished by treatment with desferrioxamine, if the iron chelation is efficient and the patients are treated for a sufficiently long period of time. Exactly how treatment with desferrioxamine works remains a challenge for further investigation.

Adolescent↗
PubMed1996

Serum procollagen III peptide concentration in iron overload.

Patients with severe iron overload may develop hepatic fibrosis due to iron toxicity. Unfortunately, the follow-up of the fibrogenic activity during treatment by histological examination of tissue biopsies carries potential side effects, and may therefore not be justified ethically. Recently, the serum concentration of procollagen type III peptide (S-PIIINP) has been shown to be a valid serum marker of the activity of collagen metabolism in conditions with hepatic fibrosis unrelated to iron overload. In order to evaluate the potential usefulness of this test in patients with fibrosis due to iron overload, we investigated the relationship between the PIIINP serum concentration and the size of iron overload in 18 patients with hereditary haemochromatosis (HH) and in 14 patients with transfusional iron overload. A close correlation was found between S-ferritin and S-PIIINP (r = 0.73, p < 0.0001). Follow-up of 6 patients during iron depletion treatment revealed a normalization of the serum aminotransferase concentration before normalization of S-PIIINP was found. This may indicate that excess iron directly induces an increase in fibrogenesis rather than the increased fibrogenesis is secondary to hepatocellular injury caused by iron excess. Thus, serial measurements S-PIIINP may be useful in follow-up of the fibrogenic process due to iron overload.

Biomarkers↗
PubMed1995

[Erythropoiesis in myelodysplastic syndrome detected by multiparameter flow cytometry].

By staining human bone marrow cells with a monoclonal antibody reacting with surface antigens on erythroid precursor cells (AS-E1) and with propidium iodide reacting with nuclear DNA, we have evaluated the proliferative activity of erythropoiesis in patients with myelodysplastic syndromes using flow cytometric analysis. Comparing 36 patients (13 RA/RAS, 13 RAEB, 10 RAEB-t) with seven normal controls, significant differences in both the percentage of erythroid precursor cells and the fraction of these cells in the S or S-G2M-phase of the DNA cell cycle between the four groups were found. Since neither the percentage of erythroid precursor cells nor their fraction in S or S-G2M phase alone was found to characterize their proliferative activity, we calculated the proliferative fractions of the erythroid cells, i.e. the number of the erythroid precursor cells in S or S-G2M related to all bone marrow cells in S or S-G2M phase. Applying these parameters, we found significantly increased proliferative fractions of erythroid precursor cells in the RA/RAS patients compared to the normal controls (p-0.03 and 0.002 respectively), as well as a highly significant decrease with disease progression.

Cross-Sectional Studies↗
PubMed1995

Translocation (1;16) identified by chromosome painting, and PRimed IN Situ-labeling (PRINS). Report of two cases and review of the cytogenetic literature.

We used the molecular cytogenetic in situ techniques chromosome painting and PRimed IN Situ labeling (PRINS) to elaborate the cytogenetic observations in two cases of the rare aberration der(16)t(1;16), which occurs in a wide variation of hematologic and nonhematologic malignancies [1-3]. Review of the literature showed that, in contrast to the chromosome 1 breakpoint, the breakpoint on chromosome 16 is associated with diagnosis as well as patient age.

Adult↗
PubMed1995

Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients.

The ability to quantitate transfusional iron overload is crucial for determining the need for and the efficacy of chelation therapy in patients with long-standing transfusion-dependent anaemias. We evaluated the usefulness of some indirect measures of iron overload in estimating the iron concentration in the liver--the most important iron storage organ--in 26 non-chelated adult non-thalassaemic patients. Liver iron concentration was determined non-invasively by magnetic resonance imaging (MRI). The standard error of the estimated liver iron concentration was 80 mumol Fe/g dried liver tissue when using the number of transfused blood units, and 93 mumol Fe/g when using a serum ferritin assay. Follow-up in 11 patients (12-48 months) revealed that serum ferritin is a poor measure of the liver iron concentration during iron chelation. However, this discrepancy was individually different and seemed to be dependent on the erythropoietic marrow activity. By monitoring the liver iron concentration by MRI, we compared the efficacy of chelation with desferrioxamine given either by subcutaneous continuous infusions or by bolus injections. Depletion of liver iron stores could be achieved efficiently by both regimens.

Adolescent↗
PubMed1994

Population pharmacokinetics of vancomycin in neonates.

OBJECTIVE: To determine population pharmacokinetic parameters of vancomycin in neonates. METHODS: This was a retrospective design, with prospective validation. Two hundred ten sequential neonates were evaluated at the neonatal intensive care units of Minneapolis Children's Medical Center and Children's Hospital of St. Paul. Five hundred twenty serum concentrations from 192 patients were included. A mean +/- SD gestational age of 29.5 +/- 5.1 weeks, postnatal age of 16.5 +/- 19.6 days, and dosing weight of 1492 +/- 1053 gm described the population. Thirty additional patients were studied for validation. Dosing, serum concentrations, and 28 covariates were collected. Data were evaluated with NONMEM. Forward selection and backward elimination regression identified significant covariates. One- and two-compartment population pharmacokinetic parameters and predictive performance of the models were measured. RESULTS: Two-compartment final regression equations were as follows: Clearance (CL) = 0.0590 L/kg/hr (multiplied by 0.460 if exposed to dopamine and 0.643 if gestational age was < or = 32 weeks), central volume (VC) = 0.440 L/kg, intercompartmental clearance (Q) = 0.0313 L/hr/kg, and steady-state volume of distribution (Vss) = 0.764 L/kg. Interindividual variability was 40.6% for CL, 54.1% for Vss, and 16.8% for VC. Residual variability was 3.3 micrograms/ml. One-compartment final regression equations were: CL = 0.0626 L/kg/hr (multiplied by 0.455 if exposed to dopamine and 0.656 if gestational age was < or = 32 weeks), and Vd = 0.496 L/kg. Differences in relative performance were insignificant by use of one- or two-compartment parameters. CONCLUSIONS: Gestational age < or = 32 weeks and concurrent use of dopamine were significant factors in prediction of vancomycin clearance. alpha Half-lives of 2.8 to 3.7 hours and beta half-lives of 13.4 to 33.7 hours suggest that some individuals in this neonatal population have considerably longer half-lives than those previously reported.

Cohort Studies↗
PubMed1994

Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging.

We investigated the clinical usefulness of a standard magnetic resonance imaging (MRI) system for non-invasive determination of the liver iron concentration in 38 patients with iron overload and 15 normal controls by measurement of the signal intensity ratio between liver and skeletal muscle (SIR). However, SIR was found dependent on the applied repetition time (TR) of the MRI system, which led us to investigate this relationship in autopsy material of liver and muscle tissue specimens with various iron content. Based on these results, adjustment of SIR measurements to a constant value of TR was achieved. By use of this technique we found a close correlation between MRI and chemically determined liver iron concentration (r2 = 0.98) as well as the serum ferritin concentration (r2 = 0.86). The reproducibility was sufficiently good for the use of MRI in the follow-up of iron reductive treatment. The use of iron store parameters in serum was found insufficient as indicators of endpoint for venesection therapy, if 20 mumol Fe/g dry weight was applied as the upper reference limit of the liver iron concentration. It is concluded that MRI based on SIR measurements offers a precise and reproducible non-invasive method for the determination and follow-up of iron overload within a wide range of liver iron concentrations. Our findings may increase the clinical use of MRI in haematological patients with iron overload.

Bloodletting↗
PubMed1994

The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin.

The concentration of carbohydrate-deficient transferrin in serum (CDT) has been used as a reliable indicator of recent alcohol consumption. We have investigated the utility of this laboratory test in 20 patients with hereditary haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver transaminases, gamma-glutamyl transpeptidase, iron, transferrin and assessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phlebotomies. In all 11 patients intensive but not maintenance iron removal was associated with an increase in serum CDT, in three patients even to levels above the reference range. The mean serum CDT increased from 8.5 (SD 2.2) U/l to 16.6 (SD 7.2) U/l (P < 0.001). Iron mobilization from the liver was found particularly responsible for the increase in serum CDT. Independent of this finding we found a significant semi-logarithmic correlation (r = -0.77, P = 0.009) between the MRI determined liver iron concentration and serum CDT in the patients not on iron depletion. Our findings indicate that the utility of serum CDT as a measure of alcohol consumption in patients with HH may be compromised, especially during intensive iron depletion.

Adult↗
PubMed1993

Heart transplantation in a case of juvenile hereditary haemochromatosis followed up by MRI and endomyocardial biopsies.

Cardiac involvement in hereditary haemochromatosis (HH) is a poor prognostic sign and is the main cause of death in the juvenile form. The treatment of choice is iron removal therapy by phlebotomy, but treatment by iron chelation (desferrioxamine) has been recommended in cases with severe cardiac symptoms. We describe here the first case of juvenile HH undergoing heart transplantation, which became necessary despite intensive iron removal therapy by phlebotomy and treatment by desferrioxamine. Throughout the course the myocardial iron content was monitored by endomyocardial biopsies and by magnetic resonance imaging (MRI). At the last follow-up, 18 months after transplantation, the myocardial iron content in the transplanted heart was still within reference ranges by biochemical determination and MRI and the patient's condition was completely satisfactory. In conclusion, heart transplantation should be considered in cases of severe juvenile HH. In the follow-up of these patients MRI may be a useful supplement.

Adult↗