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Biomedical subjects

R M Huisman

Publications and source records attributed to R M Huisman.

At least 37 records · Page 2Linked to original sources

Phosphate binders do not reduce bioavailability of oral cefuroxime-axetil in patients on peritoneal dialysis treatment.

Cefuroxime is a second-generation cephalosporin that can be used for the treatment of peritoneal dialysis-related peritonitis. Cefuroxime-axetil is an orally available pro-drug of cefuroxime. The effect of concomitant use of a phosphate binder on the bioavailability of cefuroxime-axetil was studied in 7 continuous ambulatory peritoneal dialysis (CAPD) patients who had not recently suffered from peritonitis. On two occasions, we measured cefuroxime levels in plasma, peritoneal effluent, and urine for 24 h after the ingestion of 1 g of cefuroxime-axetil: once together with a phosphate binder (+PB) and once without (-PB). Peak plasma concentrations (Cmax) were +PB: 22.7 mg/L (15.3-32.6) (median and range) and -PB: 23.2 mg/L (18.9-27.4). The area under the curve (AUC) of the plasma levels was +PB: 364 mg h/L (247-530) and -PB: 368 mg h/L (296-438). The plasma elimination half-life (t1/2) was +PB: 13.9 h (11.5-14.6) and -PB: 13.8 h (12.2-15.4). Cefuroxime concentrations in the peritoneal effluent from the first exchange were 1.9 mg/L (0.5-6.2) (+PB) and 3.4 mg/L (2.1-4.7) (-PB). In the peritoneal effluent from the second up to the last exchange, the cefuroxime levels were stable at +PB: 5.0 mg/L (2.0-8.8) and -PB: 5.3 mg/L (1.8-7.5). The total amount of cefuroxime excreted into peritoneal effluent and urine was +PB: 82 mg (30-124), -PB: 100 mg (36-129). So Cmax, AUC, t1/2 and the total amount of excreted cefuroxime were not different. Therefore, the bioavailability of cefuroxime-axetil is not reduced by the use of a phosphate binder.

Administration, Oral↗

Differences in erythrocyte sodium transport between human plasma and artificial medium: the role and character of sodium efflux and influx stimulating plasma factors.

The main objective of this study was to further characterize the plasma factor(s) which stimulate sodium efflux from erythrocytes, which we reported previously. Dialysis of plasma against an artificial medium using membranes with varying molecular mass cut-off points revealed relative molecular mass(es) of the factor(s) of 100-1000 Da. The factor(s) could be absorbed on Dowex at pH 1.5 and Amberlite at pH 11.0, indicating 'Zwitterionic' character. They are hydrophilic and resistant to acid hydrolysis. These characteristics and direct measurements of contents made amino acids likely candidates for the efflux stimulating properties of the factor(s). Indeed, plasma amino acids added to artificial medium could abolish the sodium efflux difference between plasma and the artificial medium. The efflux stimulating effect of amino acids appeared not to be the result of sodium influx stimulation. A coincident finding was that plasma also contains dialyzable sodium influx stimulating factor(s) which are not amino acids.

Adult↗

Changes in renal function induced by ACE-inhibition in the conscious two-kidney, one-clip Goldblatt hypertensive dog.

In order to study why the diagnostic sensitivity of 123I-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of 125I-iothalamate and 131I-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 +/- 5 to 4 +/- 2 ml/min, p less than 0.05), ERPF (from 111 +/- 13 to 21 +/- 10 ml/min, p less than 0.05) and UV (from 0.86 +/- 0.15 to 0.075 +/- 0.045 ml/min, p less than 0.05), whereas RBF of the poststenotic kidney slightly increased (from 193 +/- 18 to 237 +/- 27 ml/min, p less than 0.05). The concentration of hippurate and thalamate in the blood remained remarkably constant while the excretion of the tracers by the poststenotic kidney diminished and renal retention of 123I-hippurate was seen on the renogram. In 2 dogs, the experiments were repeated during mannitol infusion. In that situation, there was a much smaller decrease of poststenotic UV and GFR whereas ERPF even showed a small increase comparable to the RBF changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

The mechanism and diagnostic value of angiotensin I converting enzyme inhibition renography.

The effect of angiotensin converting enzyme (ACE) inhibition on the sensitivity of radionuclide renography in the diagnosis of a unilateral renal artery stenosis was tested both in a conscious dog model and in the human situation. ACE inhibition (10 mg enalaprilic acid, intravenously) markedly improved the sensitivity of [123I]hippuran renography in 10 renovascular hypertensive dogs with a mild to moderate unilateral renal artery stenosis from 50 to 100%. This improved sensitivity was due to an ACE-inhibition-induced delayed tracer handling at the stenotic side without an appreciable change in the renographic curve at the contralateral side. A similar phenomenon was observed in 15 hypertensive patients with an angiographically proved unilateral renal artery stenosis. Both [123I]hippuran and 99mTc-diethylenetriaminepentaacetic acid (DTPA) handling was delayed on the stenotic side after oral enalapril treatment. However, only a moderate increase in sensitivity was observed comparing control renograms to ACE-inhibition renograms: from 87 to 93% for hippuran, and from 60 to 86% for DTPA. Eight of these 15 patients underwent either surgery or angioplasty resulting in a successful correction of the stenosis. Hypertension was more or less cured in five patients. Each of these patients had shown an ACE-inhibition-induced change in the renogram at the stenotic side, suggesting that such a response may predict the curability of the hypertension. However, of the three patients that showed no blood pressure change upon successful revascularization, two showed a positive ACE-inhibition renogram. In conclusion, in an ideal setting as obtained in animal experiments, ACE inhibition improves the sensitivity of renographic studies to 100%. However, its value in the clinical setting needs more standardization.

Animals↗

Human plasma contains low molecular weight factors which stimulate active sodium transport in erythrocytes.

The aim of this study was to establish whether differences in sodium efflux rate constants (ke) in human erythrocytes occur when artificial media are compared with plasma. Using a 22Na tracer method, a mean total ke of 0.49 +/- 0.10 h-1 and significantly (p less than 0.05) lower ke values in Hanks' solution (0.43 +/- 0.08 h-1) and Basic Salt Solution (0.37 +/- 0.07 h-1) were observed. Exhaustive dialysis of plasma against Hanks' solution over a membrane with relative molecular mass cut-off of 1000 Da resulted in a decrease of the plasma total ke value to that measured in Hanks' solution. After equilibrium dialysis of plasma against Hanks' solution a decrease of total ke was found in plasma and an increase of the ke in Hanks' solution was measured. The data suggest the presence of an excess of dialyzable, active sodium transport stimulating plasma factor(s) with relative molecular mass below 1000 Da.

Adult↗

A new constrictor device for external induction of a long-term stable and irreversible renal artery stenosis in the dog.

A new externally adjustable constrictor device for renal artery stenosis in the dog is described. The constrictor combines hydraulic and mechanical characteristics, and is connected to the exterior of the animal by a thin catheter. Applying hydraulic pressure via the catheter causes the plunger in the device to compress the renal artery to any desired degree of stenosis. A mechanical catch prevents backward movement of the plunger, thus ensuring a stable, irreversible renal artery constriction. This constrictor was implanted in 13 dogs, together with an electromagnetic blood flow sensor around a renal artery. In twelve dogs the constriction procedure was performed 3-12 weeks after implantation, and in all 12 cases the intended degree of stenosis [defined as percentage renal blood flow reduction (RBF)] was achieved within a range of 10%. In 5 dogs the long-term stability of the stenosis was studied and the RBF reduction appeared to be stable up to at least 6 weeks after constriction. In conclusion, the presented constrictor device is easily externally adjustable, and allows induction of a stable renal artery stenosis of various degrees in the conscious dog.

Animals↗

Angiotensin converting enzyme inhibition induces alterations to hippuran renography despite unchanged ipsilateral renal blood flow in conscious two-kidney, one clip Goldblatt hypertensive dogs.

We performed experiments in the two-kidney, one clip Goldblatt hypertensive dog to see whether angiotensin converting enzyme (ACE) inhibition could improve the sensitivity of hippurate renography in detecting renal artery stenosis. Ten dogs on a sodium-restricted diet were studied before and after induction of a renal artery stenosis. In the absence of renal artery stenosis nine dogs showed normal renograms before ACE inhibition, and one was false positive. During ACE inhibition all 10 renograms were normal. With a renal artery stenosis 50% of the renograms were false negative, whereas a 100% sensitivity was reached during ACE inhibition. The alterations induced by the ACE inhibition on the renograms were not related to changes in renal blood flow. In conclusion, ACE inhibition markedly improved the sensitivity of hippurate renography in the two-kidney, one clip dog.

Angiotensin-Converting Enzyme Inhibitors↗

Angiotensin converting enzyme inhibition improves diagnostic procedures for renovascular hypertension in dogs.

In renovascular hypertension adaptive mechanisms in the poststenotic kidney are a probable cause of the 20 to 25% false-negative findings during rapid sequence urography or [123I]o-iodohippurate renography. We blocked the renin-angiotensin system in an effort to increase the yield of these diagnostic procedures. Chronically instrumented, salt-depleted conscious dogs were used in which a light (n = 5), moderate (n = 4), or severe (n = 2) renal artery stenosis was induced. Before stenosis 10 of the dogs showed no left-right differences with either diagnostic procedure, and angiotensin converting enzyme (ACE) inhibition did not change this result. Two to 3 weeks after induction of a renal artery stenosis, all dogs showed signs of renovascular hypertension. However, only 50% of the renograms and 22% of the urograms showed differences between the two kidneys indicative of the presence of stenosis. After ACE inhibition, all previously negative test results became positive (abnormal) and previously existing left-right differences became more evidence. Electromagnetically measured renal blood flow on the stenotic side did not change during ACE inhibition (146 +/- 13 vs 145 +/- 21 ml/min), whereas contralateral blood flow showed a distinct increase (207 +/- 18 vs 282 +/- 20 ml/min, p less than 0.01). In conclusion, ACE inhibition markedly improves the sensitivity of rapid sequence urography and hippurate renography in the diagnosis of renovascular hypertension in the two-kidney, one clip Goldblatt hypertensive dog. The effects of ACE inhibition on the handling of the different tracers do not appear to be related to its effects on renal blood flow or systemic blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗

Nephrotic syndrome preceding Hodgkin's disease by 42 months.

A 52-year-old man developed minimal change nephrotic syndrome which responded only partially to prednisolone. The addition of cyclophosphamide resulted in a complete remission. During a second episode of nephrotic syndrome prednisolone and cyclophosphamide only gave a partial remission. During a third episode, 42 months after the initial presentation, Hodgkin's disease clinical stage IA was diagnosed. Mantle field radiation therapy was given after which proteinuria gradually decreased to zero in the course of 17 months. The patient has remained free of disease until now (15 months).

Cyclophosphamide↗

Pharmacological zero for electromagnetic renal blood flow measurement.

Measurement of blood flow in chronically instrumented laboratory animals using electromagnetic flow probes depends on a reference "zero flow" value. The latter is usually obtained by mechanical vessel occlusion. We tested an alternative method: a bolus of angiotensin II was injected in the abdominal aorta resulting in an immediate decrease of renal blood flow. Diastolic blood flow at this stage appeared to be identical to the zero level obtained by mechanical occlusion. Thus, pharmacological interruption of renal blood flow may serve as a zero reference in the dog.

Angiotensin II↗