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Biomedical subjects

T Jensen

Publications and source records attributed to T Jensen.

At least 73 records · Page 4Linked to original sources
PubMed1997

No effect of unfractioned or low molecular weight heparin treatment on markers of vascular wall and hemostatic function in incipient diabetic nephropathy.

OBJECTIVE: The high risk for cardiovascular disease in IDDM patients with nephropathy may be mediated by abnormal function of the vascular wall. We investigated whether heparin was able to modulate markers of vascular wall and hemostatic function in patients with incipient nephropathy. RESEARCH DESIGN AND METHODS: Thirty-five IDDM patients with incipient nephropathy were randomized to treatment with placebo, unfractioned heparin, or low molecular weight heparin in a double-blind trial. The treatment was given as 1 h of conventional intravenous high-dose treatment and in a conventional subcutaneous low-dose regime for 3 months. Transcapillary escape rate of albumin and plasma levels of von Willebrand factor, fibrinogen, prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, tissue type plasminogen activator, tissue plasminogen activator inhibitor type 1, total cholesterol, HDL cholesterol, and triglycerides were measured before and after treatment. Of the patients, 31 completed the study. RESULTS: We found no significant effect of heparin on markers of vascular wall and hemostatic function by any of the treatments. CONCLUSIONS: Treatment with high- or low-dose heparin induced no modulation of markers of vascular wall or hemostatic function in IDDM patients with incipient diabetic nephropathy.

Adult↗
PubMed1997

Cryptococcosis in Denmark: an analysis of 28 cases in 1988-1993.

A total number of 31 events of systemic cryptococcal infection in 28 patients was identified in a nation-wide survey over 6 years from 1988 to the end of 1993. All medical records were reviewed, 24 of the patients were HIV-infected. Meningitis was diagnosed in 25 patients, and fungemia in 8 patients. The most frequent symptom was headache followed by fever. The median duration in days of fever, headache, and other neurological signs/symptoms before diagnosis was 12, 8 and 2 days, respectively, and, after diagnosis and start of treatments 7, 11 and 12 days, respectively. There was a significant correlation between the duration of headache and the duration of neurological signs/symptoms but not between headache and fever. More than 50% of the patients died within 5 months after the diagnosis. In 39% of the cases, the patients were orally treated with various antifungal drugs before the diagnosis. The rate of cryptococcosis (cumulative) in Danish AIDS patients was estimated to be 1.7%. The HIV-positive patients were, at the time of the cryptococcal diseases, profoundly immunocompromised, with a median CD4+ cell count of 18 (range: 0-78)/microliters. From 24 patients at least 1 isolate of Cryptococcus neoformans was typed, all being var. neoformans, identical with serotype A/D.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Double-homograft repair of truncus arteriosus with severe truncal valve dysfunction.

An infant with truncus arteriosus and severe dysfunction of the truncal valve including both stenosis and insufficiency successfully underwent primary repair. This included the insertion of two separate valved homograft conduits. Early outcome has been excellent and the patient is doing well after 6 months with only echocardiographic evidence of mild aortic valve regurgitation. Double-homograft repair is a realistic option in cases of truncus arteriosus with severe malformation of the truncal valve.

Echocardiography, Doppler↗
PubMed1996

Didecanoyl phosphatidylcholine is a superior substrate for assaying mammalian phospholipase D.

Phospholipase D (PLD) activity in crude or solubilized membranes from mammalian tissues is difficult to detect with the current assay techniques, unless a high radioactive concentration of substrate and/or long incubation times are employed. Generally, the enzyme has to be extracted and partially purified on one column before easy detection of activity. Furthermore, PLD activity in cultured cells can only be detected by the available assay techniques in the presence of guanosine 5'-[gamma-thio]-triphosphate (GTP[S]) and a cytosolic factor [usually ADP-ribosylation factor (Arf)]. In this paper we report that the use of didecanoyl phosphatidylcholine (C10-PC) in mammalian PLD assays considerably increases the detection limit. C10-PC was compared with the commonly used dipalmitoyl phosphatidylcholine (C16-PC) as a substrate for PLD activity from membranes of human neutrophils, human placenta and pig brain, and from placental cytosol. C10-PC was superior to C16-PC by a factor of 2-28 depending on assay conditions and tissue, and it allowed the detection of GTP[S]-and Arf-stimulated PLD activity without addition of phosphatidylinositol 4,5-bisphosphate.

ADP-Ribosylation Factors↗
PubMed1996

Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin dependent diabetes.

OBJECTIVE: To examine whether slightly elevated urinary albumin excretion precedes development of atherosclerotic vascular disease in patients with insulin dependent diabetes independently of conventional atherogenic risk factors and of diabetic nephropathy. DESIGN: Cohort study with 11 year follow up. SETTING: Diabetes centre in Denmark. SUBJECTS: 259 patients aged 19-51 with insulin dependent diabetes of 6-34 years' duration and without atherosclerotic vascular disease or diabetic nephropathy at baseline. MAIN OUTCOME MEASURES: Baseline variables: urinary albumin excretion, blood pressure, smoking habits, and serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor. END POINT: atherosclerotic vascular disease assessed by death certificates, mailed questionnaires, and hospital records. RESULTS: Thirty patients developed atherosclerotic vascular disease during follow up of 2457 person year. Elevated urinary albumin excretion was significantly predictive of atherosclerotic vascular disease (hazard ratio 1.06 (95% confidence interval 1.02 to 1.18) per 5 mg increase in 24 hour urinary albumin excretion, P = 0.002). Predictive effect was independent of age; sex; blood pressure; smoking; serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor; level of haemoglobin A(lc); insulin dose, duration of diabetes, and diabetic nephropathy (hazard ratio 1.04 (1.01 to 1.08) per 5 mg increase

Adolescent↗
PubMed1996

T cell recognition of Tn-glycosylated peptide antigens.

The mouse hemoglobin-derived decapeptide Hb (67-76), VITAFNEGLK, which binds well to Ek and is non-immunogenic in CBA/J mice, was O-glycosylated with the tumor-associated carbohydrate Tn (alpha-D-N-acetylgalactosamine, or alpha-D-GalNAc). Each of the ten positions in the peptide was substituted with serine or threonine having the Tn antigen attached. The complete set of Tn-glycosylated peptides were then studied for binding to Ek and for immunogenicity in CBA/J mice. All of those glycopeptides which had the Tn attached to serine or threonine at a position in the peptide where, according to the crystal structure determinations, the amino acid side chain was oriented downwards into the binding site of the major histocompatibility complex (MHC) molecule, completely lost their capacity for binding to Ek. This was the case for the glycopeptides with Tn attached at position 68 and 76, which are the major anchor residues and for those with Tn attached at position 71 and 73, which function as secondary anchor residues. Those glycopeptides which had Tn attached to serine or threonine at positions where the side chain pointed away from the binding site maintained their capacity for binding to Ek, except for those with Tn attached at position 70 and 74. Furthermore, some of the MHC-binding glycopeptides were immunogenic. In particular, this was the case for the glycopeptide with Tn attached to the central position 72 in the decapeptide. From previous studies, this is known to be the dominant T cell receptor contact residue of Hb (67-76). The results suggest that T cells may be capable of recognizing epitopes which are partially defined by a small glycan group.

Amino Acid Sequence↗
PubMed1996

Both alpha and beta chain polymorphisms determine the specificity of the disease-associated HLA-DQ2 molecules, with beta chain residues being most influential.

We compared the peptide binding specificity of three HLA-DQ molecules; HLA-DQ(alpha1(*)0501, beta1(*)0201), HLA-DQ(alpha1(*)0201, beta1(*)0202), and HLA-DQ(alpha1(*)0501, beta1(*)0301). The first of these molecules confers susceptibility to celiac disease and insulin-dependent diabetes mellitus, while the two latter molecules, which share either the alpha chain or the nearly identical beta chain with HLA-DQ(alpha1(*)0501, beta1(*)0201), do not predispose to these disorders. The binding of peptides was detected in biochemical binding assays as inhibition of binding of radiolabeled indicator peptides to affinity-purified HLA-DQ molecules. Binding experiments with several peptides demonstrated a clear difference in peptide binding specificity between the three HLA-DQ molecules. Further, single amino acid substitution analyses indicated that the HLA-DQ molecules have different peptide binding motifs. The experimental data were corroborated by computer modelling analysis. Our data suggest that the three HLA-DQ molecules prefer large hydrophobic residues in P1 of peptides with subtle differences in side-chain preferences. HLA-DQ(alpha1(*)0501, beta1(*)0201) and HLA-DQ(alpha1(*)0201, beta1(*)0202) both prefer large hydrophobic residues in P9, whereas HLA-DQ(alpha1(*)0501, beta1(*)0301) prefers much smaller residues in this position. HLA-DQ(alpha1(*)0501, beta1(*)0201) and HLA-DQ(alpha1(*)0201, beta1(*)0202), in contrast to HLA-DQ(alpha1(*)0501, beta1(*)0301), prefer negatively charged residues in P4 and P7. A less prominent P6 pocket also appears to differ between the three HLA-DQ molecules. Our results indicate that polymorphic residues of both the alpha and the beta chain determine the peptide binding specificity of HLA-DQ(alpha1(*)0501, beta1(*)0201), but that the beta chain polymorphisms appears to play the most important role. The information on peptide residues which are advantageous and deleterious for binding to these HLA-DQ molecules may make possible the prediction of characteristic features of peptide that bind to HLA-DQ(alpha1(*)0501, beta1(*)0201) and precipitate celiac disease.

Amino Acid Sequence↗
PubMed1996

A simplified whole blood enzyme-linked immunosorbent assay (ProTrac II) for tacrolimus (FK506) using proteolytic extraction in place of organic solvents.

Tacrolimus (FK506) is a macrolide antibiotic with potent immunosuppressive properties. FK506 is 10- to 100-fold more potent than cyclosporin A in preventing organ rejection and in toxicity. Extreme inter- and intrapatient variability and lack of correlation between drug dosage and drug blood levels necessitate consistent and reliable therapeutic drug monitoring. Previous methods for monitoring drug levels have been lengthy and labor intensive and have required organic solvents for sample extraction. We have developed a manual enzyme-linked immunosorbent assay (ProTrac II ELISA) that employs standardized reagents and a nonorganic solvent extraction and yields good assay sensitivity and precision. The calculated mean sensitivity of the assay was 0.18 ng/ml. Interassay precision ranged from 6.3% to 13.1% (coefficient of variation) for FK506 in whole blood (concentration range, 1.0-25.0 ng/ml). Recovery of the drug from spiked EDTA whole blood was 91-98% over the same concentration range. Mean recovery of the drug from clinical samples spiked with kit standards was 99.5%. Dilutions of high-concentration spiked EDTA whole blood samples and high-concentration samples from patients exhibited linearity of observed versus expected values (y = 0.86x - 1.15; r = 0.99). Comparison of ProTrac II with the INCSTAR ProTrac FK506 ELISA by paired Student's t test showed no statistical difference between the methods (p = 0.46). Comparison of ProTrac II ELISA to the IMx microparticle enzyme immunoassay (MEIA) by linear regression resulted in a line with a slope of 1.22 (r = 0.91). Analysis by t test resulted in a p value < 0.001, indicating that the absolute values obtained in these assays are significantly different. The mean (+/-SD) difference in the absolute values was 4.2 +/- 2.6 ng/ml, with the MEIA values consistently higher. These results indicate that ProTrac II is a sensitive, precise ELISA for the determination of tacrolimus in whole blood; it can be performed in < 4 h.

Drug Monitoring↗
PubMed1996

Clinical manifestations and molecular epidemiology of five cases of diarrhoea in children associated with Vibrio metschnikovii in Arequipa, Peru.

In April 1994, Vibrio metschnikovii was isolated from five infants with watery diarrhoea in Arequipa, Peru, as part of a passive cholera surveillance system. The children ranged in age from 11 to 20 months and had acute diarrhoea, with two cases showing moderate dehydration. Two children also had traces of blood in liquid stool. The children were seen at two different hospitals, and no evidence of a common source of infection was found. No additional V. metschnikovii isolates were identified in the remaining surveillance period that covered the rest of 1994 and 1995. However, stool samples were not screened for enteric pathogens other than vibrios. V. metschnikovii strains isolated from stool samples produced opaque and translucent colonies on agar plates, suggesting capsular material. All isolates were resistant to ampicillin, erythromycin and streptomycin. Plasmid analysis revealed a common 200-kb plasmid in isolates from all cases and an additional 2.7-kb plasmid in three of the isolates. Ribotyping of each isolate after restriction with BglI and HindIII endonucleases demonstrated identical ribotyping patterns. The cases reported suggest that V. metschnikovii may be associated with diarrhoea in man by mechanisms so far unknown.

Acute Disease↗
PubMed1996

Human blood-feeding rates among sympatric sibling species of Anopheles quadrimaculatus mosquitoes in northern Florida.

We compared rates of feeding on human hosts for blood-engorged female Anopheles quadrimaculatus species A, B and C1 collected from daytime resting sites in Manatee Springs State Park, Levy County, Florida during 1992-1993. Quick-blot DNA probes were used to identify mosquito taxa and also the presence of human blood in the mosquito gut. In collections from a campground area, human blood-feeding rates differed significantly among mosquito species (10.7% [19 of 177], 0%, [0 of 62], and 1.2%, [4 of 327]), respectively for species A, B and C1). In collections from a woodland site (1 km from the campground), 1.5% (2 of 129) of the species B females had fed on humans, whereas none of 19 species A or 159 species C1 females had done so. Of the three species in this study area, species A appears the most likely to be a biting pest of humans and a vector of human malaria.

Animals↗
PubMed1996

Insulin secretion and insulin sensitivity in people with impaired glucose tolerance.

To assess the roles of pancreatic beta-cell (beta-cell) dysfunction and insulin resistance in the pathogenesis of non-insulin dependent diabetes mellitus, we used euglycaemic hyperinsulinaemic and hyperglycaemic clamps to compare insulin secretion and insulin sensitivity in Caucasian individuals of European ancestry with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Both groups were carefully matched for age, gender, obesity and body fat distribution. During the hyperglycaemic clamps, IGT had significantly lower first phase (650 +/- 60 vs 992 +/- 92 pmol l-1, p = 0.001) and second phase (231 +/- 24 vs 326 +/- 21 pmol l-1, p < 0.001) plasma insulin responses while their insulin sensitivity index (0.126 +/- 0.012 mumol kg-1 pM-1) was not significantly different from that of NGT (0.144 +/- 0.012 mumol kg-1 min-1 pM-1), p = 0.69). Similarly, during the euglycaemic hyperinsulinaemic clamps, the insulin sensitivity index of the IGT (0.076 +/- 0.005 mumol kg-1 min-1 pM-1) was not significantly different from that of the NGT (0.086 +/- 0.007 mumol kg-1 min-1 pM-1), p = 0.28. We conclude that since beta-cell dysfunction is already evident in people with impaired glucose tolerance but insulin resistance is not, impaired insulin secretion is most likely the primary genetic factor predisposing to the development of non-insulin dependent diabetes mellitus in Caucasians of European ancestry.

Blood Glucose↗
PubMed1996

Magnetic resonance imaging of blood velocity distribution around St. Jude medical aortic valves in patients.

BACKGROUND AND AIMS OF THE STUDY: Complications after replacement of diseased heart valves with mechanical prostheses may be related to fluid dynamic disturbances. Magnetic resonance velocity mapping may allow quantitative, non-invasive, serial assessment of the blood velocity distribution around prosthetic heart valves in patients. MATERIAL AND METHODS: Velocity mapping was performed in six patients with aortic St. Jude Medical valves. Axial velocity components were measured at three positions near the valve and correlated with earlier in vitro results and with earlier invasive measurements. RESULTS: The velocity profiles downstream of the valve prostheses reflected the valve design and thus confirmed previous findings. In the one diameter downstream position blood flow velocities accelerated initially through the lateral orifices of the valve. Later in the acceleration phase the velocity profile became skewed and the antegrade velocity components increased in the part of the vessel corresponding to the central slit of the valve. Retrograde velocities occurred in part of the lateral orifice regions. CONCLUSIONS: MR velocity mapping provides valuable information on velocity fields around prosthetic bileaflet aortic valves. The velocity fields from the present study disclose qualitative similarity to those previously obtained. The present study, however, suggests a more skewed velocity profile than predicted from former studies. More extensive studies on larger patient groups should be performed, also with other valve types in order to establish a bank of reference data.

Adult↗
PubMed1995

[Acute schistosomiasis (Katayama fever)].

Acute schistosomiasis (Katayama fever) may present with a broad spectrum of symptoms three to six weeks after primary infection by Schistosoma (S) mansoni, S. japonicum or, more rarely, S. haematobium. The acute phase of schistosomiasis is frequently confused with other feverish diseases. It occurs almost exclusively in nonimmune visitors to endemic areas. We describe seven cases of acute S. mansoni infection. The pathogenesis, clinical features, diagnosis and treatment are briefly discussed. Katayama fever should be considered in patients returning from endemic areas with fever and eosinophilia. Clinically normal, but potentially exposed travel companions should be examined as well. Early diagnosis and treatment may be important in preventing the infection's serious sequelae of the infection.

Acute Disease↗
PubMed1995

Aspects of haemostatic function in healthy subjects with microalbuminuria--a potential atherosclerotic risk factor.

Microalbuminuria, i.e., slightly elevated urinary albumin excretion rate (UAER), notifies increased risk for atherosclerotic disease and may reflect an early generalized vascular abnormality in healthy subjects. This study was designed in order to examine whether such abnormality is associated with a shift of the haemostatic balance in prothrombotic direction. The following haemostatic factors were measured in two representative groups of clinically healthy subjects, 28 with microalbuminuria (UAER of 6.6-150 micrograms/min) and 60 age- and sex-matched controls with normoalbuminuria (UAER < 6.6 micrograms/min): Coagulation factors: blood platelet count and mean volume, plasma Factor VII antigen concentration and coagulant activity, and plasma concentrations of prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, fibrinogen, and fibrinopeptide A; fibrinolytic and endothelial factors: plasma concentrations of tissue plasminogen activator antigen and plasminogen activator inhibitor type 1 antigen; and endothelial factor: plasma von Willebrand factor antigen concentration. The fibrinolytic and endothelial factors were measured both before and after 10 minutes of venous occlusion of the arm. None of the haemostatic factors were significantly altered in the microalbuminuric group. Plasma fibrinogen concentration tended to be elevated but not statistically significant ((mean (95% C.I.) 7.8 (7.2-8.3) vs. 7.2 (6.9-7.5) mumol/l; p < 0.1). Neither did any of the haemostatic factors correlate with UAER in regression analyses. It is concluded that the haemostatic balance is unaltered in healthy subjects with microalbuminuria. It is unlikely that a prothrombotic state is present as an intermedial factor early in a causal chain between microalbuminuria and atherosclerotic vascular disease.

Adult↗
PubMed1995

Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus.

We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU unfractionated heparin, or 2000 anti-Xa IU low-molecular-weight heparin. Unfractionated and low-molecular-weight heparin induced a significant reduction in urinary albumin excretion (p = 0.04 and p = 0.004). The mechanism and clinical relevance is unknown but deserve further attention.

Adult↗
PubMed1995

Procoagulant activity and intimal dysfunction in IDDM.

The biological activity of thrombin and coagulation factor Xa was assessed in 62 insulin-dependent diabetic patients. A group of non-diabetic subjects of comparable age and urinary albumin excretion rate (< 30 mg/24 h) served as control subjects (group 1, n = 14). The patients were divided into three groups according to urinary albumin excretion rate. In group 2, albumin excretion rate was less than 30 mg/24 h (n = 17), in group 3 albumin excretion rate was in the range 30-300 mg/24 h (n = 20) and in group 4 albumin excretion rate was greater than 300 mg/24 h (n = 25). Compared to non-diabetic control subjects an increase in the biological activity of factor Xa was observed in all groups of diabetic patients (prothrombin fragment 1 + 2 levels were 1.14 +/- 0.38 nmol/l in group 2, p < 0.005; 1.06 +/- 0.45 nmol/l in group 3, p < 0.05 and 1.03 +/- 0.31 nmol/l in group 4, p < 0.05 vs 0.75 +/- 0.34 nmol/l in group 1). No difference in the level of antithrombin III was seen between the groups. We reconfirmed the presence of intimal dysfunction in diabetic nephropathy demonstrated by elevated transcapillary escape rate of albumin in group 4 compared with group 2 (8.9 +/- 2.0% vs 7.0 +/- 1.9%, p < 0.05). An overall positive correlation between transcapillary escape rate and prothrombin fragment 1 + 2 was found (r = 0.36, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Serum sialic acid concentration is elevated in IDDM especially in early diabetic nephropathy.

OBJECTIVES: Elevated serum sialic acid concentration is a strong predictor of cardiovascular mortality in non-diabetic subjects. Because patients with insulin-dependent diabetes mellitus (IDDM) and albuminuria have a highly increased cardiovascular morbidity and mortality, we hypothesized that IDDM patients with albuminuria would have an increased concentration of serum sialic acid. DESIGN: Cross-sectional study. SETTING: Outpatient clinic at Steno Diabetes Centre, Gentofte, Denmark. SUBJECTS: Twenty-six non-diabetic controls and 74 IDDM patients with normoalbuminuria (urinary albumin excretion [UAE] < 30 mg 24 h-1; n = 37), incipient nephropathy (UAE 30-300 mg 24 h-1; n = 20) and clinical nephropathy (UAE > 300 mg 24 h-1; n = 17), matched for sex, age and body mass index (BMI). MAIN OUTCOME MEASURES: Serum sialic acid concentration, concurrent fasting blood glucose, glycated haemoglobin (HbA1c), serum creatinine, plasma fibrinogen and erythrocyte sedimentation rate. RESULTS: Normoalbuminuric patients had a higher serum sialic acid concentration (mmol L-1) than non-diabetic controls (1.83 +/- 0.24 vs. 1.67 +/- 0.26; P < 0.02). Serum sialic acid concentration was further increased in patients with incipient nephropathy (2.02 +/- 0.37; P < 0.03) and in patients with clinical nephropathy (2.13 +/- 0.33; P < 0.002) compared with normoalbuminuric IDDM patients. Serum sialic acid correlated strongly with plasma fibrinogen (r = 0.78; P < 0.0001) and erythrocyte sedimentation rate (r = 0.62; P < 0.0001). In a multiple regression analysis including UAE, retinopathy status, fasting blood glucose, HbA1c, mean blood pressure, serum creatinine, age, BMI, duration and smoking. UAE and fasting blood glucose were the independent variables which correlated significantly with serum sialic acid concentration (P < 0.0001 and P < 0.05, respectively). CONCLUSION: Serum sialic acid is elevated in IDDM especially in albuminuric patients. Whether elevated serum sialic acid is predictive for early diabetic nephropathy and cardiovascular disease in IDDM has to be shown in the future.

Adult↗