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Biomedical subjects

R W Jansen

Publications and source records attributed to R W Jansen.

At least 37 records · Page 2Linked to original sources

Validation of multifrequency bioelectrical impedance analysis in monitoring fluid balance in healthy elderly subjects.

BACKGROUND: Multifrequency Bioelectrical Impedance Analysis (MFBIA) is a novel method to assess body composition in elderly subjects. However, it is unclear whether MFBIA can detect changes in body water compartments in elders. We aimed to determine the within-subject variability of MFBIA and the responsiveness to a diuretic intervention in aged subjects with a stable fluid balance. METHODS: We selected 12 healthy active elderly subjects (5 male, 7 female) with a mean age of 75 years. Total body water and extracellular fluid (ECF) were measured by deuterium oxide- and potassium bromide-dilution techniques. Within-subject variability in total body MFBIA was assessed by performing four measurements at 1, 5, 50, and 100 kHz within a 2-month period. Subsequently, responsiveness of MFBIA to the ECF loss caused by oral administration of 40 mg of furosemide was determined. RESULTS: Within-subject variability in MFBIA at 1, 5, 50, and 100 kHz expressed as standard deviations was 21, 19, 14, and 14 Ohm (omega), respectively. Furosemide caused a mean weight loss of 1.8 +/- 0.6 kg, which resulted in significant increases in impedance of 57 +/- 24 omega at 1 kHz and 37 +/- 12 omega at 100 kHz (p < .001). The responsiveness of MFBIA for the diuretic intervention was best at 5 kHz (responsiveness index = 1.98). CONCLUSIONS: Within-subject variability of MFBIA was small in healthy elderly subjects with stable fluid balance. Responsiveness of MFBIA to 9% furosemide-induced ECF loss was excellent. These data support the necessity for further clinical assessment of the value of MFBIA in monitoring fluid balance in geriatric patients.

Aged↗

Validation of multi-frequency bioelectrical impedance analysis in detecting changes in fluid balance of geriatric patients.

OBJECTIVES: Multi-Frequency Bioelectrical Impedance Analysis (MFBIA) is a quick, simple, and inexpensive method to assess body fluid compartments. This study aimed at determining the validity of MFBIA in detecting clinically relevant changes of fluid balance in geriatric patients. DESIGN: A prospective, observational study. SETTING: The 22-bed Geriatric Department of the University Hospital Nijmegen. PARTICIPANTS: Hospitalized patients were eligible if they did not have a pacemaker, were not suffering from terminal illnesses, and did not have psychogeriatric diseases likely to interfere with capacity to consent or comply. During a 16-months period, 218 patients were admitted, of whom 78 patients were eligible and 53 consented to participate. MEASUREMENTS: Each subject's fluid balance was diagnosed twice a week as dehydrated, overhydrated, or euvolemic, based on standardized physical examination, laboratory tests, and weight evaluation. Changes in fluid balance were quantified by measuring total body water (TBW) and extracellular fluid (ECF) applying deuterium- and bromide-dilution techniques. Impedance at 1, 5, 50, and 100 kHz and body weight were measured daily. Sensitivity and Guyatt's responsiveness indexes of MFBIA in detecting dehydration and overhydration were determined. RESULTS: In total, 1071 MFBIA measurements were performed, during which 14 transitions from dehydration to euvolemia and 13 transitions from overhydration to euvolemia were monitored. Rehydration of dehydrated patients caused an increase in TBW and ECF of 3.4 +/- 1.8 L and 1.9 +/- 1.9 L, respectively, which resulted in significant decreases in impedance of 133 +/- 67 omega at 1 kHz and 93 +/- 61 omega at 100 kHz (P = .001). Treatment of overhydrated patients caused a TBW and ECF loss of 3.8 +/- 4.2 L and 3.1 +/- 3.8 L, respectively, which resulted in significant increases in impedance of 104 +/- 72 omega at 1 kHz and 81 +/- 68 omega at 100 kHz (P < .001). Sensitivity of a single MFBIA in diagnosing dehydration and overhydration was 14% and 17%, respectively. Responsiveness indexes of weighing and MFBIA for dehydration and overhydration were similar at all frequencies and greater than one. CONCLUSION: The sensitivity of a single impedance measurement in detecting dehydration and overhydration was low. However, responsiveness of serial measurements to intra-individual changes in fluid balance was good. Therefore, this noninvasive technique may be used in clinical practice to improve monitoring fluid balance in geriatric patients, especially when daily weighing is difficult.

Activities of Daily Living↗

Diuretic usage and withdrawal patterns in a Dutch geriatric patient population.

OBJECTIVES: To describe diuretic usage and withdrawal patterns in a population of very old geriatric patients and to evaluate the long-term probability of remaining free from diuretic therapy after withdrawal. DESIGN: Retrospective analysis of medical records and 1-year follow-up study. SETTING: University Hospital Nijmegen and Rijnstate Hospital Arnhem, a non-academic teaching hospital, The Netherlands. PARTICIPANTS: All 1547 patients, aged 75 years or older, visiting geriatric medicine departments in the two hospitals for the first time in the years 1990 through 1993. MEASUREMENTS: Data on medical history, physical examinations, and medication use were obtained from medical records. Diuretic withdrawal and motivation was recorded as reported. Record review indicating diuretic withdrawal prompted a 1-year follow-up investigation and collection of additional updated information from family care and/or nursing-home physicians. RESULTS: A total of 593 three patients (38.3%) were using diuretics. Use of diuretics increased with age from 33.6% in patients aged 75 to 79 years to 47.4% in patients aged 90 years or older (P < .05). Diuretics were withdrawn in 218 patients (36.8%), in 101 patients because of doubts about the initial or persistent indication for diuretic use and in 91 patients because of adverse effects. No reasons for withdrawal were reported in 26 patients. Withdrawal of diuretics was attempted more often in cases of diuretic prescriptions for unknown reasons (51.2%) or ankle edema without heart failure (45.0%) than when prescriptions were for heart failure (28.5%) or hypertension (35.4%). The overall probability of remaining free of diuretic therapy for 1 year was 0.41. Success of diuretic withdrawal was significantly less when congestive heart failure was the initial indication for prescription (probability 0.24). We did not find other clinical parameters related to the success of withdrawal. CONCLUSIONS: Our study demonstrates that diuretic therapy can be withdrawn for at least a 1-year period in a substantial number of very old geriatric patients receiving these medications, regardless of the initial indications for prescription. However, withdrawal is performed without application of uniform criteria. Future prospective studies should be directed at developing clear guidelines for diuretic withdrawal in order to facilitate identification of eligible patients and to further improve the success of withdrawal attempts.

Age Factors↗

Intraindividual reproducibility of postprandial and orthostatic blood pressure changes in older nursing-home patients: relationship with chronic use of cardiovascular medications.

OBJECTIVES: Although postprandial and orthostatic hypotension are commonly observed in nursing home residents, their reproducibility, relationship to each other, and association with chronic use of cardiovascular medications are poorly understood. DESIGN: We examined blood pressure (BP) and heart rate (HR) before and after postural change, and before and after a 419-kcal meal in 22 nursing home residents (mean age 89 +/- 5 (SD) years), each on two occasions, to determine reproducibility changes. These studies were repeated in 17 residents, with and without previous administration of cardiovascular medications, in random order. SETTING: Hebrew Rehabilitation Center for the Aged, an academic long-term care facility. RESULTS: Systolic BP declined an average (+/- SE) of 16 +/- 4 mm Hg and 12 +/- 4 mm Hg during the first and second meal studies, respectively. Mean intra-class correlation of postprandial systolic BP values during the two studies was 0.88 (95% CI 0.85-0.97). Systolic BP increased significantly during the first posture test to a maximum of 8 +/- 6 mm Hg at 6 minutes. There was no significant difference over time in postural systolic BP between the two tests. Repeated postural studies showed a mean intra-class correlation of 0.72 (95% CI 0.62-0.92) for changes in systolic BP. Cardiovascular medications had no additional effect on postprandial or orthostatic BP and HR changes. During the first studies, 10 subjects had postprandial hypotension, and three subjects had orthostatic hypotension, but only two of 22 subjects had both. CONCLUSIONS: Patterns of systolic BP response to meals or postural change are reproducible. BP responses to meals and postural change seem to be unaffected by potentially hypotensive medications in chronic users. Postprandial hypotension is distinct from orthostatic hypotension, occurring more commonly than orthostatic hypotension and infrequently together in the same patients.

Aged↗

(-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (524W91) inhibits hepatitis B virus replication in primary human hepatocytes.

The anti-hepatitis B virus (HBV) activity of (-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (524W91) in cultures of primary human hepatocytes was examined. 524W91 was anabolized to the active 5'-triphosphate in these cells. HBV replication was equally inhibited in cultures incubated with 524W91 when the drug was added 24 h preinfection, at infection, or 24 h postinfection. 524W91 inhibited HBV replication by 50% at less than 20 nM in human hepatocytes.

Antiviral Agents↗

Postprandial hypotension in elderly patients with unexplained syncope.

BACKGROUND: Syncope in older patients may be caused by a variety of disorders, including hypotension, but frequently remains unexplained. Postprandial hypotension is a common disorder of blood pressure regulation in the elderly. OBJECTIVE: To determine the pathogenic mechanisms and potential role of postprandial hypotension in elderly patients with otherwise unexplained syncope. METHODS: We studied 16 elderly patients with unexplained syncope and nine elderly controls. Blood pressure, heart rate, forearm vascular resistance, plasma norepinephrine level, and cardiac and splanchnic blood volumes were measured before and after a 1680-kJ meal. RESULTS: Eight elderly patients with syncope had postprandial hypotension, with a decline in supine mean arterial blood pressure of 17 +/- 2 mm Hg after a meal (P < .001). The blood pressure remained unchanged after the meal in the other patients with syncope and the controls. In patients with postprandial hypotension, systemic vascular resistance fell after the meal, while it remained unchanged in the other groups. Heart rate and plasma norepinephrine level increased to a similar extent in all three groups. Forearm vascular resistance increased only in the control subjects. Splanchnic blood volume increased by 26% (P < .01) in patients with syncope who had postprandial hypotension and by 22% (P < .01) in control subjects. Splanchnic blood volume remained unchanged in the patients with syncope without postprandial hypotension. CONCLUSIONS: Postprandial hypotension may be an important causative factor in elderly patients with unexplained syncope. The evaluation of syncope in elderly patients should therefore include blood pressure measurements surrounding a meal. Elderly patients with syncope who have postprandial hypotension fail to maintain systemic vascular resistance, probably because of splanchnic blood pooling without a compensatory increase in peripheral vascular resistance.

Aged↗

Postprandial hypotension: epidemiology, pathophysiology, and clinical management.

OBJECTIVE: To show the clinical relevance of postprandial hypotension and to review its pathophysiology and management. DATA SOURCES: Articles on postprandial hypotension were identified through MEDLINE and bibliographies of relevant articles. STUDY SELECTION: All articles and case reports describing meal-related hypotension in the elderly and in patients with autonomic failure. DATA SYNTHESIS: Postprandial hypotension, defined as a decrease in systolic blood pressure of 20 mm Hg or more, may result in syncope, falls, dizziness, weakness, angina pectoris, and stroke. Postprandial hypotension is distinct from and probably more common than orthostatic hypotension. Because meal-related hypotension is particularly common in older hypertensive patients, it has important implications for the evaluation and management of hypertension. The mechanism of postprandial hypotension is not fully understood. Possible contributors include inadequate sympathetic nervous system compensation for meal-induced splanchnic blood pooling; impairments in baroreflex function; inadequate postprandial increases in cardiac output; and impaired peripheral vasoconstriction, insulin-induced vasodilation, and release of vasodilatory gastrointestinal peptides. Although caffeine is often recommended as treatment for postprandial hypotension, available data do not support its use. Octreotide, a somatostatin analog, has been shown to be effective, but it is expensive and must be given parenterally. CONCLUSION: All physicians caring for elderly patients should be aware of the hypotensive effects of food intake and should consider postprandial hypotension in the evaluation of syncope, falls, dizziness, and other cerebral ischemic symptoms.

Age Factors↗

A model and diagnostic measures for response time series on tests of concentration: historical background, conceptual framework, and some applications.

Based upon classical hypotheses about accumulating mental fatigue and distraction and its effect on response times, put forward in late 19th and early 20th century papers, a mathematical model is proposed for response times on tests of speed and concentration. The model assumes the random occurrence of very short distractions during information processing. It explains fluctuation and the increasing trend in response times on successive equivalent task units and leads to some simple diagnostic RT measures of speed and concentration as alternatives to the mean RT. A review is given of several experimental applications of the model, with subjects with and without concentration problems, using cancellation and digit addition tasks. The results demonstrate the potential usefulness of the model and the diagnostic measures derived from it. As predicted by the model, prolonged task performance yields an increasing trend in RT mean and variance that can be strongly reduced by giving very short resting periods very frequently, and to a lesser extent also by task alternation, but not by simply motivating the subjects to concentrate. Some practical implications for the administration and scoring of tests of speed and concentration are discussed, as well as limitations of the present results and the complementary relation of our approach to popular ones such as "stage analysis."

Adult↗

Haemodynamic and neurohumoral effects of caffeine in elderly patients with symptomatic postprandial hypotension: a double-blind, randomized, placebo-controlled study.

1. The aim of this study was to determine the effects of caffeine on haemodynamic and neurohumoral responses to meal ingestion in elderly patients with a history of symptomatic postprandial hypotension. 2. Postprandial hypotension is a common disorder of blood pressure regulation in the elderly, associated with falls and syncope. The pathophysiological mechanism is thought to be related to impaired vascular compensation for splanchnic blood pooling after a meal. Since caffeine inhibits vasodilatory adenosine receptors in the splanchnic circulation, we postulated that caffeine would reduce splanchnic blood pooling and prevent the development of postprandial hypotension. 3. We conducted a randomized, double-blind, placebo-controlled, cross-over study in nine elderly patients [age 76 +/- 9 (SD) years] with histories of symptomatic postprandial hypotension. Standardized 1674kJ liquid meals with 250 mg of caffeine or placebo were given on two occasions, at least 1 week apart. Blood pressure, heart rate, forearm vascular resistance (by venous occlusion plethysmography), and plasma caffeine and catecholamine levels were measured. Cardiac and splanchnic blood volume were determined by radionuclide scans. 4. By 30 min after both caffeine and placebo meal studies, supine mean arterial blood pressure fell significantly (P = 0.006) by 31 +/- 7 and 19 +/- 6 mmHg, respectively (mean +/- SEM, between group difference was not significant). Heart rate, cardiac output and splanchnic blood volume increased significantly, but to a similar extent, after caffeine and placebo. Forearm vascular resistance was unchanged after both meals. 5. Oral caffeine given with a meal does not reduce splanchnic blood pooling nor prevent postprandial hypotension in symptomatic elderly patients.

Aged↗

Inhibition of hepatitis B virus in tissue culture by alpha interferon.

Alpha-n1 interferon (Wellferon), alpha-2a interferon (Roferon), and alpha-2b interferon (Intron-A) inhibited accumulation of intracellular replicative forms of hepatitis B virus (HBV) in chronic producer cells by inhibiting accumulation of RNase-resistant HBV RNA. In contrast, the nucleoside analog FTC (cis-5-fluoro-1- [2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine) inhibited the accumulation of HBV DNA.

Cell Line↗

Evaluation of the potent anti-hepatitis B virus agent (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in a novel in vivo model.

A murine model was developed to investigate the in vivo activity of anti-hepatitis B virus (HBV) agents. Mice with subcutaneous tumors of HBV-producing 2.2.15 cells showed reductions in levels of HBV in serum and in intracellular levels of HBV when the mice were orally dosed with (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC). No effects on tumor size or alpha-fetoprotein levels were observed. FTC can selectively inhibit HBV replication at nontoxic doses.

Animals↗

Hepatic and intrahepatic targeting of an anti-inflammatory agent with human serum albumin and neoglycoproteins as carrier molecules.

The anti-inflammatory agent naproxen (Nap) was covalently coupled to human serum albumin (HSA) and to the neoglycoproteins, galactose and mannose terminated HSA, to deliver this drug selectively to different cell types of the liver. Disposition of Nap20-HSA was studied in rats and compared to that of equivalent doses of mixtures of uncoupled drug and protein. The liver to kidney ratios of the drug (L/K-Nap) and the protein (L/K-prot.) were increased, indicating an improved delivery of both protein and drug to the target site. After injection of 10 micrograms Nap20-HSA the L/K-prot. was increased 15.0 +/- 0.21-fold as measured 1 hr after injection. Even after injection of 5 mg of the conjugate, the L/K-prot. was enhanced 5.6 +/- 0.34-fold and the L/K-Nap 4.6 +/- 0.23-fold as measured 1 hr after injection. Immunohistochemical staining of liver slices revealed that the endothelial cells were the main sites for hepatic uptake. Further pharmacokinetic studies of Nap20-HSA in isolated perfused rat livers showed a saturable uptake process (Vmax = 2.46 micrograms/min/10.0 g liver and Km = 4.27 x 10(-6) M). The uptake in the liver could be inhibited by various polyanionic probes, indicating the major involvement of a scavenger receptor system in the internalization mechanism of Nap20-HSA. This endothelial uptake via the scavenger receptor system is likely to be related to the increased negative charge of the Nap-albumin conjugate as was revealed by anion exchange chromatography. Studies in the intact organ and in purified liver lysosomal lysates indicate that after internalization of Nap20-HSA the conjugate is proteolytically degraded leading to the formation of the lysine conjugate of Nap. This amino acid conjugate of Nap was shown in a previous study by us to be equipotent to Nap itself with regard to prostaglandin-E2 synthesis inhibition. A pronounced altered intrahepatic distribution was observed when Nap was coupled to lactosaminated and mannosylated HSA (Lact-HSA and Man-HSA, respectively). Coupling of Nap to Lact27-HSA and Man10-HSA resulted in a major shift in intrahepatic distribution from endothelial cells to the hepatocytes and Kupffer cells, respectively. We conclude that conjugation of Nap to HSA itself results in a selective delivery to endothelial cells and that the local proteolysis of the conjugate produces an active catabolite. Selective delivery to other cell types of the liver can be achieved by attaching naproxen to neoglycoproteins with an appropriate type and number of sugar groups.

Animals↗

Reproducibility of the finger cooling test.

A finger cooling test is used to objectify Raynaud's phenomenon and to assess its severity. For this purpose, finger skin temperature (FST) and laser Doppler flux (LDF) are measured on the fingertips before and during cooling of the hand (16 degrees water bath for 5 min) and a subsequent recovery period (20 min). To study reproducibility, this test was performed twice within 3 months in 34 healthy subjects and in 56 Raynaud patients. Three test parameters were used in the analysis: the baseline value, the value after 12 min of recovery, and the mean level during recovery. We determined the limits of agreement (mean differences between the first and the second test +/- 2SD) and the coefficients of variation. No systematic differences between the first and the second test were found. Outside temperature did not influence FST or LDF. FST was shown to have a better reproducibility than LDF. For the baseline value in the total group the coefficient of variation was 3.3% for FST and, rather high, 21.6% for LDF. The limits of agreement for the baseline value in the total group were -4.8 to 4.2 degrees for FST and -25.2 to 22.2 arbitrary units for LDF. In conclusion, the applied cooling test has limited value in individual cases, but can be useful when comparing large groups in pathophysiologic or therapeutic studies.

Adult↗

Pharmacokinetic analysis and cellular distribution of the anti-HIV compound succinylated human serum albumin (Suc-HSA) in vivo and in the isolated perfused rat liver.

After intravenous injection of a low dose (25 micrograms/kg) in rats, the anti HIV-1 compound succinylated human serum albumin (Suc-HSA) is taken up mainly in the liver and spleen and is proteolytically degraded. Ten minutes after injection of 125I-Suc-HSA, 72 and 14% of the dose were found in the liver and spleen, respectively. With immunohistochemistry we demonstrated that in both organs, Suc-HSA was specifically endocytosed in endothelial cells. In the isolated perfused rat liver preparation, liver uptake was shown to be saturable, with a Km of 2.9 10(-8) M and a Vmax of 2.4 micrograms/min/100 g body weight. The apparent Km and Vmax in vivo were 2.2 10(-7) M and 10.3 micrograms/min/100 g, respectively. Uptake in liver and spleen was inhibited by preadministration of an excess of formaldehyde-treated albumin and with polyinosinic acid, indicating the involvement of the scavenger receptor, as anticipated for such polyanionic compounds. Suc-HSA is not absorbed intact from the colon and the ileum. After injecting (i.v.) rats with a high dose of Suc-HSA (10 mg/kg), the elimination t1/2 was 3 hr, and therefore, sustained plasma levels above the concentration needed for in vitro anti-HIV-1 activity can be achieved.

Animals↗

High-capacity in vitro assessment of anti-hepatitis B virus compound selectivity by a virion-specific polymerase chain reaction assay.

An integrated assessment system specific for hepatitis B virus (HBV) Dane particle DNA was developed to examine the activity of potential anti-HBV compounds in chronic HBV-producing HepG2-derived 2.2.15 cells. Cell culture, immunoaffinity purification, polymerase chain reaction, and hybrid-capture detection were performed in the microtiter format to facilitate increased throughput by automation. The high sensitivity afforded by the assay provided quantitative detection of less than 0.5 fg of extracellular HBV DNA from 25 microliters of cell culture supernatants, and drug-induced reductions in HBV titers greater than 100-fold were easily measured. Fluorometric determination of total cellular DNA from the same 96-well proliferating cell cultures allowed simultaneous evaluation of inhibition of cell growth, thus providing the ability to assess the overall selectivities of candidate compounds in a single experiment. The potent activities of three anti-HBV compounds, the (+) and (-) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxythiolane-5-yl]cytosine (FTC) and D-carbocyclic-2'-deoxyguanosine (CDG), were confirmed by this method. (-)-FTC was more active than its (+) enantiomer (50% inhibitory concentrations, 0.033 +/- 0.006 and 0.723 +/- 0.160 microM [standard error of the mean; SEM], respectively), while both enantiomers demonstrated a lack of cytotoxicity at 200 microM. CDG was more potent (50% inhibitory concentration, 0.0063 +/- 0.0007 microM [SEM]) but was also significantly more toxic, inhibiting cell growth by 50% at 32 +/- 6 microM (SEM). These results demonstrate the usefulness of this immunoaffinity-based, quantitative polymerase chain reaction system as a high-capacity in vitro tool for assessment of anti-HBV compound selectivity.

Antibody Specificity↗

Coupling of the antiviral drug ara-AMP to lactosaminated albumin leads to specific uptake in rat and human hepatocytes.

We covalently coupled 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) to the carrier molecule lactosaminated human serum albumin using a water-soluble carbodiimide with a two-step conjugation method (pH 4.5 and pH 7.5) instead of the commonly used single-step conjugation at pH 7.5. This resulted in a predominantly monomeric conjugate (lac27-HSA-ara-AMP9). The conjugate was stable in buffer (pH 7.4) and blood plasma. After in vivo injection, the carrier and the monomeric conjugate were subjected to selective endocytosis in rat hepatocytes, as shown on immunohistochemical study and cell-separation techniques using 125I-labeled material. In competition experiments with other ligands for the asialoglycoprotein receptor N-acetylgalactosamine and asialofetuin, we showed that both lactosaminated human serum albumin and lac27-HSA-ara-AMP9 are subject to endocytosis by this receptor system. Although the coupling of ara-AMP significantly increased the net negative charge of the conjugate compared with the native carrier, liver uptake was not affected by coadministration of an excess of succinylated human serum albumin (suc-HSA), a negatively charged ligand for the scavenger receptor. Incubation studies with purified rat liver lysosomes showed that in this acidic and proteolytic environment, mainly ara-AMP and, to a much lesser extent, ara-A itself were released from the carrier. After injection into the rat in vivo and in isolated perfused rat liver, no free ara-AMP or 9-B-D-arabinofuranosyladenine (ara-A) could be detected in plasma and perfusate, respectively, indicating proper retention of the virally active components in hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗