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Biomedical subjects

T Jensen

Publications and source records attributed to T Jensen.

At least 145 records · Page 8Linked to original sources

Clinical experiences with fusidic acid in cystic fibrosis patients.

A survey of Staphylococcus aureus lung infection in 243 patients with cystic fibrosis (CF) was conducted between 1986 and 1988. A total of 217 patients (89%) received 1605 courses of anti-staphylococcal therapy given during this period. The majority of courses comprised combined therapy with two anti-staphylococcal drugs. The combination of dicloxacillin and fusidic acid was employed most frequently. Some patients were given other anti-staphylococcal regimens, because of penicillin allergy (14 cases) or dyspeptic side effects with fusidic acid (21 patients). A small but significant increase in precipitins against S. aureus was observed during the study period. Bacterial resistance to the anti-staphylococcal drugs used remained at a low level (strains resistant to methicillin less than 0.1%, strains resistant to fusidic acid 1.2%). When the isolates were compared with 56,140 strains of S. aureus isolated from non-CF patients hospitalized in Denmark over the same period, no differences in phagetypes or in antibiotic resistance were seen, indicating that selection of strains and cross infection do not seem to be a major problem in CF patients.

Bacteriophage Typing↗

Increased hepatic efficacy of urea synthesis from alanine in insulin-dependent diabetes mellitus.

The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and in 18 patients with insulin-dependent diabetes mellitus (HbAlc = 8.4 +/- 1.0% (mean +/- SD)). Following an overnight fast alanine was infused at 2 mmol h-1 kg-1 body weight. The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water and intestinal hydrolysis. The functional hepatic nitrogen clearance, i.e. the relation of urea synthesis rate to blood alanine concentration, was calculated as the slope of linear regression of urea synthesis rates on blood alanine concentrations. Fasting glucagon concentrations were 85 +/- 26 ng l-1 in controls and 161 +/- 35 ng l-1 (P less than 0.01) in patients. The functional hepatic nitrogen clearances were 21.8 +/- 4.4 l h-1 in controls and 44.7 +/- 12.4 l h-1 (P less than 0.001) in patients. By multiple step-wise linear regression analysis the functional hepatic nitrogen clearance was found to correlate independently to fasting glucagon concentration, duration of diabetes, change in blood glucose and insulin following alanine infusion (r2 = 0.74). In a simple linear regression analysis the functional hepatic nitrogen clearance correlated strongly to fasting glucagon concentration (r2 = 0.54). In conclusion the kinetics of urea synthesis in insulin-dependent diabetes is changed in favour of increased conversion of alanine-N to urea-N at any blood amino acid concentration. The increased FHNC correlates strongly with hyperglucagonaemia.

Adult↗

Effects of octreotide on lipoproteins and endothelial function of type 1 (insulin-dependent) diabetic patients.

Hypersecretion of growth hormone (GH) is a characteristic feature of Type 1 diabetic patients. In healthy subjects growth hormone is able to induce an increase in endothelial cell proteins such as fibrinogen and von Willebrand factor. Plasma concentrations of such proteins, which are markers of cardiovascular risk, are elevated in diabetic patients with microalbuminuria, suggesting endothelial cell dysfunction. In a randomized prospective study we therefore evaluated the possible effects of 1 year's treatment with a somatostatin analogue, octreotide, on lipoproteins and on endothelial function in Type 1 diabetes mellitus. Seven patients were allocated to treatment with a continuous subcutaneous infusion of 400 micrograms octreotide per day. Seven patients served as a control group. During treatment a decrease in plasma LDL-cholesterol (2.62 (2.17-3.11) (median (range] vs 2.00 (1.89-2.96) mmol l-1, p less than 0.05) and serum apolipoprotein A-I (1.47 (1.25-1.60) vs 1.23 (1.13-1.90) g l-1, p less than 0.05) was observed in the treated group. Furthermore a probable reduction during treatment in plasma concentrations of von Willebrand factor (1.72 (0.84-3.04) vs 1.24 (0.94-1.82) U ml-1, p = 0.08) and fibrinogen (11.3 (7.3-25.3) vs 8.1 (7.5-11.8) mumol l-1, p = 0.06) was found, and after withdrawal of treatment an increase towards the initial levels was seen. The platelet count declined (326 (301-612) vs 217 (206-400) x 10(9) l-1, p less than 0.01) during octreotide treatment and remained depressed 2 months after withdrawal.

Adult↗

Nephrotoxicity of cyclosporin A in patients with newly diagnosed type 1 diabetes mellitus.

Renal function was studied in 18 patients with Type 1 diabetes mellitus. All were participating in the Canadian-European randomized placebo-controlled cyclosporin trial in newly diagnosed Type 1 diabetic patients, nine being randomized to placebo, and nine to cyclosporin A. During treatment for 12 to 18 months, cyclosporin A caused significant reductions in the glomerular filtration rate (before drug withdrawal, cyclosporin 97 +/- 18 vs placebo 125 +/- 16 ml min-1 1.73-m-2, p less than 0.05), renal plasma flow (454 +/- 83 vs 536 +/- 70 ml min-1 1.73-m-2, p less than 0.05), and lithium clearance (17 +/- 3 vs 28 +/- 5 ml min-1 1.73-m-2, p less than 0.05). The fractional proximal reabsorption was increased (0.82 +/- 0.03 vs 0.78 +/- 0.03, p less than 0.05), and the fractional distal sodium reabsorption reduced (0.88 +/- 0.03 vs 0.94 +/- 0.02, p less than 0.05). These results are in accordance with the hypothesis that the nephrotoxic effect of cyclosporin A results from a preferential constriction of afferent glomerular vessels. One year after withdrawal of the drug, all variables were similar in the two groups, except for blood glucose control which was worse in the cyclosporin A treated group. When corrected for differences in blood glucose control it appeared that in three out of nine patients glomerular filtration rate had not completely returned to the reference range of the placebo group. We conclude that the nephrotoxic side-effects of cyclosporin A treatment for 1 year are reversible. There are, however, signs of minor and perhaps chronic renal injury.

Adult↗

Immunoglobulin A and immunoglobulin G antibody responses to alginates from Pseudomonas aeruginosa in patients with cystic fibrosis.

Patients with cystic fibrosis have a high prevalence of mucoid, alginate-producing Pseudomonas aeruginosa that causes chronic infection of the mucosal surface of the lungs. We developed enzyme-linked immunosorbent assays (ELISAs) for determination in serum of immunoglobulin A (IgA) and IgG antibodies to alginate purified from P. aeruginosa and an ELISA for detection of IgA antibodies to a polyvalent P. aeruginosa standard antigen. Absorption experiments indicated that the assays were antigen and antibody specific and had analytical variations that ranged from 7 to 19%. Serum samples from 207 patients with cystic fibrosis, 100 healthy children, and 94 healthy adults were examined. The patients responded to P. aeruginosa infection with early IgA and IgG antibody responses that were significantly higher than in controls and noncolonized patients. Analysis of paired serum samples showed that infected patients had an increase in specific IgG and IgA antibodies that was significantly higher than in noncolonized patients. The serological data were analyzed for correlation with clinical condition; poor lung function was significantly associated with increased levels of IgA and IgG antibodies to P. aeruginosa alginate and to the standard antigen and with a relative excess of IgA antibodies to the standard antigen compared with IgA antibodies to P. aeruginosa alginate. The assays showed high predictive values if positive, but a negative test did not exclude infection, and the ELISAs should not be used for diagnostic purposes. Mucoid strains were present initially in the sputa of 28 of 54 infected patients with paired serum samples. These patients had a significant increase in anti-alginate antibodies, but it was not different from the increase seen in patients infected only with nonmucoid strains. Therefore, alginate may also be produced in vivo by nonmucoid P. aeruginosa. The study showed that early formation of IgA and IgG antibodies to P. aeruginosa alginate did not prevent development of chronic infection and that P. aeruginosa-specific IgA antibodies correlate with poor lung function.

Adolescent↗

Relationship between blood pressure and urinary albumin excretion in development of microalbuminuria.

Two hundred nine consecutive normotensive insulin-dependent diabetic (IDDM) patients were followed prospectively from November 1982 to January 1988. Patient urinary albumin excretion rate (UAE) had to be normal (less than 30 mg/24 h) on at least two occasions before inclusion in the study. Patients were aged 18-50 yr with a duration of diabetes of 10-30 yr. UAE was measured every 4 mo, and supine blood pressure was measured annually. Two hundred five patients completed the study. Five years later, 15 patients had developed persistent microalbuminuria with median UAE greater than 30 mg/24 h for at least 2 yr (group 2), and 190 patients stayed normoalbuminuric (group 1). Although within normal range, initial UAE was significantly elevated in group 2 compared with group 1 (mean 19 mg/24 h [range 15-23 mg/24 h] vs. 11 mg/24 h [10-12], 95% confidence interval [CI], P less than 0.001). Initially, there was no difference in blood pressure between group 2 (mean systolic 122 mmHg [117-127], diastolic 80 mmHg [76-84]) and group 1 (mean 126 mmHg [124-128], 79 mmHg [78-80], 95% CI), and a significant increase in diastolic blood pressure could first be detected during the 3rd yr of persistent microalbuminuria (mean systolic 132 mmHg [124-140], diastolic 85 mmHg [81-89] vs. 128 mmHg [126-130], 79 mmHg [78-80], P less than 0.05). Initial hemoglobin A1c was significantly elevated in group 2 compared with group 1 (9.6% [8.8-10.4] vs. 8.5% [8.3-8.7], P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Partial normalization by dietary cod-liver oil of increased microvascular albumin leakage in patients with insulin-dependent diabetes and albuminuria.

In a double-blind crossover study, we compared the effects of eight weeks of dietary supplementation with cod-liver oil with the effects of supplementation with olive oil on endothelial permeability, blood pressure, and plasma lipid levels in 18 patients with insulin-dependent diabetes mellitus and albuminuria. When the patients received the cod-liver-oil supplement, the mean (+/- SEM) transcapillary escape rate of albumin (as compared with the base-line rate) decreased from 8.7 +/- 0.5 to 6.9 +/- 0.6 percent per hour (P less than 0.01), and the blood pressure decreased from 146 +/- 4/90 +/- 2 mm Hg to 139 +/- 4/85 +/- 2 mm Hg (P less than 0.05). There was no correlation, however, between cod-liver oil's effect on the transcapillary escape rate of albumin and its effect on blood pressure. There was no change from base line after the patients received the olive-oil supplement. During dietary supplementation with cod-liver oil, the plasma concentration of high-density lipoprotein cholesterol increased and the concentrations of very-low-density lipoprotein cholesterol and triglycerides decreased (P less than 0.05 for all comparisons), but the level of low-density lipoprotein cholesterol did not change. In contrast, during supplementation with olive oil, the concentration of low-density lipoprotein cholesterol decreased and the levels of very-low-density lipoprotein cholesterol and triglyceride increased (P less than 0.05 for all comparisons), but there was no change in the level of high-density lipoprotein. No changes were observed in the glomerular filtration rate, degree of albuminuria, insulin requirement, glycosylated hemoglobin level, or blood glucose level during supplementation with either oil. We conclude that dietary supplementation with cod-liver oil lowers the elevated transcapillary escape rate of albumin characteristic of patients with insulin-dependent diabetes and albuminuria, independently of its effect on blood pressure--perhaps by decreasing vascular permeability. We did not find any effect of cod-liver oil on urinary albumin excretion.

Adult↗

[Reduction of mortality in acute myocardial infarction with streptokinase and aspirin therapy. Results of ISIS-2].

This investigation includes 17,187 patients in 417 hospitals in 16 countries admitted within 24 hours of the commencement of symptoms of acute myocardial infarction (AMI). The patients were allotted at random to the following treatments 1) intravenous infusion of 1.5 million International Units streptokinase (SK) during one hour, 2) 160 mg acetyl salicylic acid (ASA) daily for 30 days, 3) both SK and ASA and 4) placebo treatment only. The five-week cardiovascular mortality was reduced by 25% following infusion of streptokinase from 12.0% to 9.2% and by 23% during ASA treatment from 11.8% to 9.4%. The combination of SK and ASA resulted in 42% reduction in the cardiovascular mortality after five weeks compared with the placebo. The effect of SK was greatest if treatment was instituted within six hours but effects were obtained after all of the first 24 hours. The preliminary results show that the reduction in mortality obtained by both SK and ASA appears to continue during the subsequent one to two years. SK treatment resulted in haemorrhage requiring treatment in 0.5% as compared with 0.2% in the placebo group, more cases of proved cerebral haemorrhage, 0.1% as compared with 0.0%, but fewer cases of cerebral apoplexy, 0.7% as compared with 0.8%. It is concluded that thrombolysis with SK combined with prophylaxis of repeated thrombosis with ASA is the indicated treatment in cases of AMI and less than 6-24 hours duration.

Aged↗

Features of endothelial dysfunction in early diabetic nephropathy.

The release of tissue plasminogen activator (tPA) by vascular endothelial cells during exercise was studied in forty men with insulin-dependent diabetes. Three groups, matched for age and diabetes duration, were defined as: group I (n = 19), normal urinary albumin excretion (less than 30 mg/24 h); group II (n = 11), incipient diabetic nephropathy (30-300 mg albumin excreted per 24 h); and group III (n = 10), clinical diabetic nephropathy (more than 300 mg albumin excreted per 24 h). Nine non-diabetic men served as controls. The rise in tPA antigen with exercise was similar in the controls and group I but significantly smaller in groups II and III (p less than 0.01). The albumin transcapillary escape rate was significantly higher in groups II and III than in group I and normal controls (p less than 0.01). The basal plasma level of von Willebrand factor was higher in groups III (p less than 0.01) and II (difference not significant, p = 0.06) than in group I and normal controls. These findings suggest that insulin-dependent diabetic patients with only slightly raised urinary albumin excretion have general endothelial cell dysfunction or damage. It is not yet clear whether these changes are important in the pathogenesis of thrombosis and atherosclerosis in these patients.

Adolescent↗