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Biomedical subjects

R Jaeger

Publications and source records attributed to R Jaeger.

At least 37 records · Page 2Linked to original sources
PubMed1994

Reduced sensitivity to beta-adrenoceptor stimulation and blockade in insulin dependent diabetic patients with hypoglycaemia unawareness.

Nine IDDM-patients with hypoglycaemia unawareness, seven IDDM-patients with hypoglycemia awareness and a control group of nine healthy persons were included in this study. The patients were recruited from the medical out-patients' department of the University Hospital of Tromsø. The pathophysiological changes which cause hypoglycaemia unawareness are today not clear. Reduced peripheral tissue sensitivity to catecholamines is suggested as one of several mechanisms which may contribute. For further investigation of beta-adrenergic sensitivity an isoprenaline/metoprolol sensitivity test was performed. Isoprenaline and metoprolol were administered intravenously, and the effects on heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma levels of adrenaline (ADR) and noradrenaline (NA) were measured. All subjects were given the same doses of isoprenaline (0.25-8 micrograms) and metoprolol (0.5-8 mg). Metoprolol was given together with the dose of isoprenaline which increased heart rate by 25 beats min-1. The dose/response curves of both isoprenaline/HR and metoprolol/HR were significantly shifted to the right in IDDM-patients with hypoglycaemia unawareness compared with controls and IDDM-patients with hypoglycaemia awareness (P < 0.05). Reduced sensitivity of isoprenaline stimulation has also been shown before, whereas reduced sensitivity of a blocking agent has not earlier been shown. These findings support the hypothesis of reduced beta-adrenergic sensitivity as one pathophysiological component in hypoglycaemia unawareness.

Adult↗
PubMed1993

Effect of serum and cell density on transmembrane distribution of cAMP and cGMP in transformed (C4-I) and non-transformed (WI-38) human cells.

The ratio between cGMP and cAMP in plasma/urine is elevated in several types of malignancies. The present in vitro study showed that the ratio between extracellular cGMP and cAMP increased during the proliferation of C4-I cells (derived from a carcinoma of the uterine cervix), whereas this ratio decreased in WI-38 cells (normal lung fibroblasts). These results can be explained by differences between the transformed and non-transformed cells in the cell-density-dependent transmembrane distribution and intracellular levels of cyclic nucleotides. In the serum-deprived cultures, no profound effects were seen on the cell-density-dependent biokinetics of cAMP and cGMP. In the absence of serum, growth of C4-I cells was markedly retarded, whereas WI-38 cells were unable to expand at all.

Cell Count↗
PubMed1993

Interactions of vinblastine and vincristine with methotrexate transport in isolated rat hepatocytes.

The accumulation of methotrexate (MTX) in the presence of vinblastine (VBL) and vincristine (VCR) was studied in isolated rat hepatocytes. In accordance with our recent study on vindesine (VDS), we found VBL and VCR to reduce net MTX accumulation significantly at 15 min after MTX addition. Drug concentrations of 100 microM VBL and 500 microM VCR led to 67% and 82% reductions in intracellular MTX, respectively. Since there was only a slight inhibition of MTX efflux by 100 microM VBL, the accumulation data demonstrate that the major effect of VBL is on MTX influx. Dixon-plot analyses are suggestive of competitive inhibition of the MTX influx, yielding inhibition constants (Ki values) of 55 microM for VBL and 110 microM for VCR. Since the Ki values correspond grossly to plasma levels obtained in humans shortly after the infusion of therapeutic doses of the vinca alkaloids studied herein, the interaction with MTX uptake could serve to diminish the toxicity of MTX to nonmalignant cells.

Animals↗
PubMed1993

Electrical stimulation of the sacral dermatomes in spinal cord injury: effect on rectal manometry and bowel emptying.

The impairment in defecation function that comes as a result of spinal cord injury may have a significant negative impact upon quality of life. Electrical stimulation (ES) of the somatic nervous system has been used to elicit autonomic reflexes in animals, before and after spinal cord transection. To determine whether ES might be used to promote bowel emptying, seven persons with recent spinal cord injury (SCI) and seven control subjects were studied. Electrical stimulation of the second sacral dermatome was applied during rectal manometry in both groups, and ES was added to the bowel programs of SCI patients. A significant rise in the number of rectal pressure spikes was noted in both groups after application of ES (p < .002, f = 6.34). There was no significant differences between the SCI and control groups when measuring the amplitude of spike waves in the colon. No significant change was noted in the time required for SCI patients to initiate a bowel movement, or in the time required to complete bowel emptying. Electrical stimulation of the sacral dermatomes can result in a change in the bowel activity of the recto-sigmoid colon. To date, no clinical effect on bowel emptying has been demonstrated.

Colon↗
PubMed1993

Circulating platelet aggregates indicative of in vivo platelet activation in pulmonary hypertension.

The authors investigated the existence of circulating cellular aggregates in 12 patients with moderate to severe pulmonary hypertension, using scanning electron microscopy. Peripheral venous blood was collected in the presence of 11.5 mM buffered ethylenediaminetetraacetic acid, in order to disperse freshly formed disaggregable aggregates. Irreversible aggregates represented by platelet clusters and/or platelet attachment to either leukocytes or red cells were identified in 7 patients with pulmonary hypertension. Endogenous platelet activation was further confirmed by a significant increase in plasma levels of beta-thromboglobulin in comparison with controls (33.8 +/- 14.1 vs 22.7 +/- 11.5 ng/mL respectively, p < 0.025). The presence of irreversible aggregates in the blood stream strongly suggests that cell-cell interactions actually occur in vivo in these patients. If so, therapeutic measures aimed at preventing in situ thrombosis and its consequences may be beneficial in this disorder.

Adolescent↗
PubMed1992

Plasma protein binding of catecholamines, prazosin and propranolol in diabetes mellitus.

In the present study equilibrium dialysis has been used to determine the degree of protein binding of the catecholamines adrenaline and noradrenaline and the adrenergic receptor blockers, prazosin and propranolol in diabetics. The binding of the catecholamines in plasma from Type I and II diabetic patients was not significantly different from that of healthy subjects. The ratio of the bound and free catecholamine concentrations was correlated with the level of albumin (HSA). Significantly reduced protein binding of prazosin was observed in Type I and II diabetic subjects compared to healthy volunteers. The binding of propranolol was significantly reduced in Type I patients. The ratios between the bound and unbound concentrations of prazosin and propranolol were significantly correlated with the levels of alpha 1-acid glycoprotein (AAG). The results suggest that non-enzymatic glycosylation of plasma proteins may increase the unbound fraction of the adrenergic blockers prazosin and propranolol.

Adult↗
PubMed1992

Broth microdilution testing of Haemophilus influenzae with haemophilus test medium versus lysed horse blood broth. Canadian Haemophilus Study Group.

Broth microdilution testing of 702 community-acquired isolates of Haemophilus influenzae from across Canada was performed with both Mueller-Hinton broth supplemented with 3% lysed horse blood broth (LHB) (BBL Microbiology Systems, Cockeysville, Md.) and haemophilus test medium (HTM). The prevalence of beta-lactamase production was found to be 26% with no regional variation. MICs determined with LHB tended to be higher than those with HTM, but interpretive errors due to these differences were observed only rarely with trimethoprim-sulfamethoxazole (n = 5), cefaclor (n = 8), and cefamandole (n = 3). The interobserver variability in MIC determinations was found to be greater when LHB was used than when HTM was used. There was no difference in intraobserver variability between the two medium formulations. beta-Lactamase-positive isolates developed false resistance to amoxicillin-clavulanate 2 weeks after microdilution panels of both types of medium were stored at -20 degrees C but not when panels were stored at -70 degrees C. In conclusion, this study supports the use of HTM rather than LHB for sensitivity testing of H. influenzae because of its lower rate of interobserver variability and its ability to support the growth of these organisms, which is comparable to that of LHB.

Amoxicillin↗
PubMed1990

An automated method for the determination of nortriptyline and its isomeric 10-hydroxylated metabolites in plasma by high pressure liquid chromatography.

A high pressure liquid chromatography assay for determination of the tricyclic antidepressant nortriptyline (NT) and its two major metabolites, Z- and E-10-Hydroxy-NT, in plasma is described. Sample preparation included addition of internal standard and a single step extraction procedure. Run time was approximately 14 min. with a LC-18. 5 mu 250 x 4.6 mm column, a mobile phase consisting of aqueous ammonium: methanol: acetonitrile (0.8:6.2:93, v/v), and flow of 1.3 ml/min. NT, Z- and E-10-OH-NT, amitriptyline, Z- and E-10-OH-AT and the internal standard desipramine, were adequately separated within this time span. In our laboratory, the assay has been employed mainly for pharmacokinetic and toxicologic studies in experimental animals at relatively high concentrations.

Animals↗
PubMed1990

Comparative in vitro activities of several new fluoroquinolones and beta-lactam antimicrobial agents against community isolates of Streptococcus pneumoniae.

The in vitro susceptibilities of 551 community isolates of Streptococcus pneumoniae from the Canadian province of Ontario to several new fluoroquinolones and beta-lactam antimicrobial agents were determined by a broth microdilution technique. Eight (1.5%) of these isolates were moderately susceptible (MICs, greater than or equal to 0.12 and less than or equal to 1.0 microgram/ml) to penicillin; none was resistant. Temafloxacin, ciprofloxacin, and ofloxacin (MICs for 90% of strains tested, between 1 and 2 micrograms/ml) were the most active fluoroquinolones tested, and BMY-28100 (MIC for 90% of strains tested, 0.25 microgram/ml) was the most active of the new beta-lactams tested.

4-Quinolones↗
PubMed1989

Binding of prazosin and propranolol at variable alpha 1-acid glycoprotein and albumin concentrations.

1. The effect of variable alpha 1-acid glycoprotein (AAG) and albumin (HSA) concentrations on the binding of prazosin and propranolol was assessed in plasma after surgery and in mixtures of AAG/HSA with concentrations mimicking those found in vivo. 2. On the pre-operative day the binding of prazosin and propranolol was 94.8% and 89.0%, respectively and 97.3% and 93.2%, respectively, 5 days after surgery. 3. In solutions containing mixtures of highly purified AAG and HSA representing the pre-operative state, 88.6% and 83.9% binding of prazosin and propranolol was observed, whereas for solutions mimicking post-operative plasma, the equivalent values were 94.6% and 91.4%, respectively. 4. The ratios between bound and unbound concentrations of both drugs were closely correlated to the concentrations of AAG, but not to the concentrations of HSA. 5. The present study demonstrates that AAG is responsible for the binding variability of prazosin and propranolol in plasma from post-operative patients.

Aged↗
PubMed1989

Binding of prazosin to alpha 1-acid glycoprotein and albumin: effect of protein purity and concentrations.

Prazosin is extensively bound in human serum/plasma. In the present study a bound fraction of 93-95% was observed at 37 degrees for therapeutic drug concentrations. Both alpha 1-acid glycoprotein (AAG) and albumin (HSA) are established as transport proteins for prazosin, but their individual contribution to the extent and variability of protein binding in serum/plasma is unclear. The present study showed that AAG possesses one binding site per molecule with high affinity (Kd approximately 0.8 microM) for prazosin. HSA, essentially globulin-free, bound prazosin with lower affinity (Kd approximately 30 microM) with an average of 0.3 binding sites per molecule. However, less purified HSA, containing globulins, exhibited apparently higher affinity (Kd approximately 8 microM), but lower binding capacity (0.07 sites per molecule) for prazosin. In mixtures of highly purified proteins, the concentrations of AAG, and not HSA, determined the extent and variability of prazosin binding.

Dialysis↗
PubMed1988

Interactions with the protein binding of 7-hydroxy-methotrexate in human serum in vitro.

7-Hydroxy-methotrexate (7-OH-MTX), the major extracellular methotrexate (MTX) metabolite, is 90-95% bound in human serum, with albumin (HSA) as the major binding protein. Reports of an interaction with concomitantly administered non-steroidal antiinflammatory drugs (NSAIDs) during MTX therapy led us to investigate whether these compounds could reduce the binding of 7-OH-MTX in vitro. Equilibrium dialysis experiments demonstrated that naproxen and indomethacin concentration dependently reduced the binding of 1 microM 7-OH-MTX. After ingestion of 1000 mg naproxen, per cent unbound 7-OH-MTX in sera from volunteers increased 2-3-fold in vitro, positively correlated to naproxen concentrations (P less than 0.00015). In addition, etacrynic acid, bilirubin, sulphamethizole and acetylsalicylic acid displaced 7-OH-MTX from its binding protein(s) in a competitive manner. The data suggest that 7-OH-MTX interacts with several exogenous and endogenous substances associated with HSA in human serum. Displacement of 7-OH-MTX from HSA may contribute to the interaction between NSAIDs and MTX.

Adult↗
PubMed1988

Catecholamine binding and concentrations in acute phase plasma after surgery.

The present study was undertaken to decide whether the bound fractions and/or total concentrations of catecholamines were determinative for the variability of biologically active concentrations in human plasma. The binding and concentrations of noradrenaline (NA) and adrenalin (Adr) were determined in acute phase plasma after major hip surgery in five subjects. The bound fractions before surgery were 23.0% and 18.4% for NA and Adr, respectively. The binding of catecholamines increased in the post-operative period. Five days after surgery the binding of NA and Adr was 30.9% and 24.0%, respectively. The surgical trauma induced an acute phase reaction in plasma with a decrease of albumin (HSA) concentrations whereas the concentrations of alpha-1 acid glycoprotein (AAG) increased. The catecholamine concentrations showed a considerable inter- and intraindividual variability. However, the present work shows that the variability of the biologically active catecholamine concentrations is mainly dependent on the total plasma concentrations and not the plasma protein binding.

Acute-Phase Reaction↗
PubMed1988

Pharmacokinetics of 7-hydroxy-methotrexate and methotrexate in the rat.

To investigate the pharmacokinetics of the active metabolite of methotrexate (MTX), 7-hydroxy-methotrexate (7-OH-MTX), 1 mg/kg of the compound was administered as single intravenous bolus injections to 6 unanaesthetized rats. For comparison, 1 mg/kg of the parent drug MTX was given to the same number of animals. Venous blood samples were drawn at intervals for a total of 120 min., and thereafter the rats were sacrificed and tissue samples were obtained from the brain, lungs, liver, kidneys, testes, fat, and muscle. Pharmacokinetics of 7-OH-MTX and MTX were biphasic, with a significantly (P less than 0.05) smaller central compartment of distribution (Vc) and a longer second phase half-life (t1/2(beta)) for 7-OH-MTX. MTX tissue concentrations exceeded those of 7-OH-MTX in all tissues examined. The highest 7-OH-MTX concentrations were found in renal tissue. It is implied that 7-OH-MTX is less extensively distributed than the parent compound.

Animals↗
PubMed1988

Falls. Prevention and management in the institutional setting.

Falls are more common among nursing home than community dwelling elderly and more often result in serious injury among the nursing home population. This article reviews the epidemiology of falls in the long-term care setting, identifies risk factors associated with falling in the nursing home, and discusses possible interventions for those at high risk of falling.

Accident Prevention↗