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Biomedical subjects

M Aurell

Publications and source records attributed to M Aurell.

At least 37 records · Page 2Linked to original sources
PubMed1997

PGE2 production after angiotensin-converting enzyme inhibition.

Using OKT3 monoclonal antibody driven T-lymphocyte proliferation, we investigated the effects of plasma 10, 20 and 30% in cell cultures on the proliferation ex vivo after exposure to captopril or enalapril taken orally by healthy volunteers. We also studied the effects of captopril, angiotensin II and bradykinin in vitro. We observed a plasma dependent dual effect of ACE inhibition both ex vivo and in vitro and of bradykinin in vitro being a stimulated proliferation at low (10% plasma) and a suppression of proliferation at high (30% plasma). The suppression was shown to be PGE2 mediated but the nature of the stimulatory signal is unknown. Proliferation was also suppressed by angiotensin II mediated by PGE2, but angiotensin II had no stimulatory effect. The results indicate that the effects of ACE inhibition on OKT3 mAb driven T-lymphocyte proliferation is plasma dependent, class specific for ACE inhibitors and mediated by both the ACE inhibitor itself and by bradykinin. Furthermore, it was shown that indomethacin in combination with an ACE inhibitor or bradykinin converted a suppressive response into proliferation indicating an immunostimulatory activity by indomethacin.

Adult↗
PubMed1996

Remikiren (Ro 42-5892)--an orally active renin inhibitor in essential hypertension. Effects on blood pressure and the renin-angiotensin-aldosterone system.

Remikiren (Ro 42-5892) is a new orally active renin inhibitor with high potency and specificity in vitro. In the present study, the drug was given in a short-term study in patients with essential hypertension, either as monotherapy or with added hydrochlorothiazide. Following a wash-out period of at least 3 weeks and then 8 days of single-blind placebo, 29 patients with essential hypertension were given remikiren 600 mg orally for 8 days. After 4 days of remikiren, hydrochlorothiazide 12.5 mg or 25 mg or placebo was added in double-blind fashion for the last 4 days. There were no significant changes in blood pressure in patients given remikiren alone. In patients given additional hydrochlorothiazide for 4 days, a marked reduction in blood pressure was observed. Remikiren effectively inhibited the plasma renin activity 24 h post-dose, whereas angiotensin II was reduced only during the first hours after drug administration. It is concluded that remikiren is orally effective. Its antihypertensive effect during short-term administration was not significant, but when given with a diuretic, a marked potentiation occurred. Further studies are needed to establish the long-term effects of remikiren alone and in combination therapy.

Antihypertensive Agents↗
PubMed1996

Renal function on and off lithium in patients treated with lithium for 15 years or more. A controlled, prospective lithium-withdrawal study.

BACKGROUND: Controversy remains over the magnitude and reversibility of reduced renal function in long-term lithium patients. METHODS: Thirteen patients with 18 years (range 15-24) on lithium discontinued the treatment, and were re-examined twice after 5 and 9 weeks (4-16) off lithium. They were compared to a non-lithium psychiatric control group, matched for age and sex. RESULTS: Glomerular filtration rate (GFR) tended to improve from 69 (39-96) to 74 (39-94) ml/min/1.73 m2 BSA, P = 0.057, which was not significantly different from 78 (61-106 ml/min per 1.73 m2 BSA in the controls. Reduced GFR was found in only two of the lithium patients off lithium, and in none of the controls. Maximal urinary concentrating capacity did not improve at all. It was 637 (130-875) mOsm/kg H2O in the lithium patients, which was lower than 856 (705-1.035) mOsm/kg H2O (P < 0.01) in the controls. Two of the lithium patients had isosthenuria. CONCLUSIONS: Lithium patients often have an irreversible, clinically important reduction of Umax, sometimes progressing to nephrogenic diabetes insipidus, while GFR is well preserved in most patients.

Adult↗
PubMed1996

Consensus on diuresis renography for investigating the dilated upper urinary tract. Radionuclides in Nephrourology Group. Consensus Committee on Diuresis Renography.

UNLABELLED: There is great variation in technique and interpretation of diuresis renography between different establishments. METHODS: To address this problem, an International Consensus Committee was appointed by the Ninth International Symposium on Radionuclides in Nephrourology in 1994. RESULTS: The final document was produced and addressed: objectives, equipment, data acquisition, choice of radiopharmaceutical, patient preparation, position, dosage of furosemide, timing of furosemide, role of bladder catheter, duration of study, pediatric considerations, evaluation of the furosemide response, interpretation, and conclusion. CONCLUSION: The report presents a standardized approach to diuresis renography that, if adopted, will improve reproducibility between centers, discourage unacceptable practice and stimulate further discussion between nuclear medicine and urology health care professionals who treat patients with dilated and obstructed upper urinary tracts.

Adolescent↗
PubMed1996

Report of the Radionuclides in Nephrourology Committee on renal clearance.

The need for simple and accurate methods to measure renal function is self-evident. This need increases as techniques for intervention become available. The demand for evaluation of individual kidney function has increased with its role in the diagnosis and follow-up of unilateral renal disease and in decision making for conservative or surgical treatment based on residual renal function. The role of nuclear medicine in this area has been inhibited by confusion about conflicting methodologies. This report is meant to provide guidance to those centers that would like to initiate clearance procedures but have difficulty in choosing appropriate methodology.

Glomerular Filtration Rate↗
PubMed1995

Treatment of renovascular hypertension: one year results of renal angioplasty.

During the ten year period from 1981 to 1991, percutaneous transluminal renal angioplasty (PTRA) was performed in 180 renal arteries in 137 patients, where the underlying renovascular disease was fibromuscular dysplasia (FMD) in 30 patients (22%) and arteriosclerotic vascular disease (AVD) in 107 (78%). A preinterventional work-up and a re-evaluation of the patients after one year was designed for the assessment of the clinical, functional and technical outcome. Successful technical dilatation was achieved in 97% of procedures with FMD patients and in 82% of procedures with AVD patients. A beneficial effect on the blood pressure and the renal function was registered in both groups. The overall cure and improvement rate for hypertension was 86% in the FMD group and 64% in the AVD group after one year's follow-up. A significant gain in the total renal function was registered in both groups, the average increase in glomerular filtration rate being 13% (P < 0.001) for the FMD group and 11% (P < 0.001) for the AVD group one year after PTRA. Renal function was improved or unchanged in 89% of FMD patients and 74% of AVD patients. The improvement in renal function was made by the revascularized kidney. Renal vein renin investigation predicted the clinical outcome with an excellent diagnostic accuracy as no renin negative patient became normotensive, and renin positive patients, who did not turn normotensive, were in almost 90% of the cases affected by technical failure or restenosis/contralateral stenosis. Thus, the sensitivity of renal vein renin investigation was 95% and the specificity 75%. The outcome for patients with hypertension and renal insufficiency was considerably poorer than for the whole group of patients, with only a 20% success rate for hypertension, but 50% in this group had increased or unchanged GFR after intervention. The angiographic one-year follow-up revealed a recurrence rate of 6.7% for FMD and 15.1% for AVD. For the entire series of patients, the incidence of major complications was 5.4%, including one indirect fatality, while the incidence of minor complications was 5%. In conclusion, PTRA will cure or improve blood pressure in most patients with renovascular hypertension, and it preserves and even improves renal function in these patients. Complications and recurrence are in fact not very common and PTRA appears be the best first approach in all but ostial lesions for treatment of renovascular hypertension.

Angioplasty, Balloon↗
PubMed1994

Abnormalities in the renin-angiotensin-aldosterone system in normotensive subjects with a positive family history of hypertension.

Non-hypertensive men with a positive family history of hypertension in two generations (N = 16) were compared with weight-matched (N = 13) and lean (N = 12) control groups with a negative family history of hypertension with respect to the activity of the renin-angiotensin-aldosterone system at baseline and during an oral glucose tolerance test. Blood pressure was measured phonographically after 30 min of semirecumbent rest and the oral glucose tolerance test was performed after a 10-h overnight fast with 100 g of glucose given orally. Blood samples were drawn from a peripheral catheter at baseline, 30 and 120 min after the glucose challenge. Systolic and diastolic blood pressures did not differ between subjects with a positive or a negative family history of hypertension. At baseline, blood glucose and plasma insulin were similar in the three groups while the group with a positive family history of hypertension had a significantly lower plasma renin activity (PRA) (0.85 +/- 0.09 compared with the weight-matched but not with the lean control group (1.36 +/- 0.13 and 1.06 +/- 0.15 ng AI.ml-1.h-1; p < 0.01 and NS, respectively). The PRA increased significantly after the glucose challenge in all groups (p < 0.01), while the plasma aldosterone concentration decreased after 30 min and then showed an increase at 120 min. The PRA response was less pronounced in the group with a positive family history of hypertension compared with the weight-matched and lean control groups (p < 0.05 and p < 0.01, respectively). Serum potassium did not change significantly in either group after the glucose challenge. Urinary sodium excretion was similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Renovascular resistance in primary hypertension: experimental variations detected by means of Doppler ultrasound.

OBJECTIVE: To gauge the influence of renovascular resistance changes on blood flow velocity pulsatility in kidneys of hypertensive patients by means of the ultrasonic colour and pulsed-wave Doppler method, since we have previously shown in normotensive subjects that the blood flow velocity pulsatility in renal interlobar arteries varies with changes in renovascular resistance. METHODS: In six male patients with primary hypertension, renal blood flow velocity profiles were investigated by means of duplex ultrasound. Single-kidney renovascular resistance was assessed by measurements of split renal function (gamma-camera renography), renal plasma flow (steady-state para-aminohippurate clearance) and cuff blood pressure. The pulsatility index of the blood flow velocity spectrum in the renal interlobar artery and renovascular resistance were measured either at rest, during infusion of angiotensin II, or after angiotensin converting enzyme inhibition. RESULTS: A significant correlation existed between pulsatility index and renovascular resistance (r = 0.50, P < 0.002), which did not improve after correction for the blood pressure pulsatility. Changes of pulsatility index were more closely related (r = 0.64, P < 0.001) to the corresponding changes in renovascular resistance. CONCLUSIONS: With the two-dimensional image-guided colour and pulsed-wave Doppler method it is possible to assess semiquantitatively small intra-individual changes in renovascular resistance in hypertensive patients by means of pulsatility index measurements. Pharmacologically induced alterations in renovascular haemodynamics may therefore be evaluated with this technique.

Angiotensin II↗
PubMed1994

Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium.

The renal risks associated with long-term lithium treatment are a growing concern. We have therefore studied renal function by means of glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of 215 patients with more than 15 years of lithium treatment in nine psychiatric clinics. Data on psychiatric and somatic diseases, hospital admissions, cumulative lithium doses, and other psychotropic treatments were extracted from the medical records. The patients were investigated according to a standardized protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test. Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21% of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in 12%. Umax but not GFR was inversely correlated to the cumulative lithium dose. Kidney function was more reduced in patients on lithium combined with psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst was a complaint of 53% of the patients, predominantly those with additional psychotropics. We conclude that kidney damage is common in patients on long-term lithium treatment and that both glomerular and tubular function are affected.

Adult↗
PubMed1993

Urea kinetics during hemodialysis measured by microdialysis--a novel technique.

A microdialysis technique has been developed for estimation of concentrations of low molecular size compounds in the interstitial fluid in vivo. With this technique urea kinetics in the interstitial fluid and plasma were studied in ten patients during and after hemodialysis. There was a close correspondence between urea measurements in plasma and interstitium during hemodialysis. Urea rebound occurred in plasma during two hours after dialysis (15.8 +/- 6.5% in the first hour and 11.8 +/- 5.9% in the second hour). The urea rebound in the interstitium was delayed about 60 minutes after that of plasma (2.8 +/- 8% and 14.1 +/- 7.8% in the first and second hours, respectively) and continued for up to four hours after dialysis. The relationship between plasma urea rebound and the efficiency of hemodialysis and ultrafiltration volume was studied in 17 patients. Results showed a close relation between the fractional urea removal during dialysis and the plasma urea rebound. The contribution of de novo urea genesis to the rebound was estimated from the interdialytic increase in plasma urea concentrations, and was 17 to 24% of the plasma urea rebound during two hours postdialysis. The initial plasma urea rebound could in part result from urea influx to plasma from the enterohepatic recirculation of urea nitrogen. Plasma urea rebound should be taken into account for determination of the amount of dialysis delivered during hemodialysis.

Adult↗
PubMed1993

Renal and systemic sympathetic counterregulation in response to vasodilators in renovascular hypertension.

1. Twenty-two patients with renovascular hypertension and significant lateralization of renin secretion were investigated with respect to arterial and renal venous plasma noradrenaline and dopamine concentrations before and 30 min after two different blood pressure-lowering procedures (enalaprilat or dihydralazine intravenously). 2. In one group of patients (n = 10) blood pressure reduction by 7.5 mg of dihydralazine caused stimulation of the renin-angiotensin system and increased heart rate (P < 0.01) as well as arterial and renal venous plasma noradrenaline and dopamine concentrations (P < 0.01 for both). The elevation of the plasma dopamine concentration was more pronounced than that of noradrenaline, yielding increased dopamine/noradrenaline ratios both peripherally (P < 0.05) and in the renal veins (P < 0.05). 3. In the second group of patients (n = 12) a comparable reduction in blood pressure elicited by 1.25 mg of enalaprilat was not accompanied by alterations in heart rate or in noradrenaline or dopamine levels in arterial plasma or renal venous plasma from either kidney. 4. Thus, inhibition of angiotensin-converting enzyme does not elicit the expected sympathetic counter-regulatory response to blood pressure reduction; the mechanism(s) involved remains to be clarified.

Adolescent↗
PubMed1993

Effects of long-term antihypertensive treatment and aging on renal function and albumin excretion in primary hypertension.

The effects on renal function and urinary albumin excretion of 7 years of antihypertensive treatment compared to the effects of normal aging were studied in a random sample of 40 men with newly diagnosed primary hypertension and in 17 normotensive men of the same age, respectively. The hypertensives were treated with metoprolol either as monotherapy (n = 21) or combined with hydrochlorothiazide or hydralazine. Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; para-aminohippurate clearance), renal vascular resistance (RVR), and the 24 h urinary albumin excretion were determined. GFR was significantly reduced from 104 +/- 15 mL/min (mean +/- SD) to 86 +/- 20 mL/min (P < .001) in the hypertensive group, but the reduction was not significantly greater than in the normotensive group. As judged from the study of a subgroup of the hypertensives, most of the decrease in GFR occurred early as an immediate drug-induced, functionally explained decrease. The changes in RBF and RVR after 7 years of treatment did not differ significantly from those due to normal aging. RVR remained higher and RBF remained lower in the hypertensives than in the normotensives. The urinary albumin excretion in the hypertensives was significantly reduced after 7 years but remained higher than in the normotensives. In conclusion, the changes in renal function and hemodynamics seen after long-term treatment with metoprolol in primary hypertension were not significantly different from the changes caused by normal aging in normotensives.

Aging↗
PubMed1993

Reliability of ACE inhibitor-enhanced 99Tcm-DTPA gamma camera renography in the detection of renovascular hypertension.

Twenty consecutive patients with renovascular hypertension, proven by cure or improvement of hypertension at 1-year follow-up after percutaneous transluminal angioplasty or surgical repair, were studied before intervention by means of gamma camera renography with 99Tcm-diethylenetriaminepentaacetic acid (99Tcm-DTPA) at baseline and after angiotensin-converting enzyme (ACE) inhibition. Sixteen patients underwent bilateral renal vein catheterization for measurement of renal vein renin release and extraction ratios of para-amino-hippurate (PAH) and 51Cr-EDTA before and after acute ACE inhibition. With the limit for a significant change in relative side distribution of 5% or more after ACE inhibition on gamma camera renography 13 patients responded (Group 1), while seven patients (Group 2) had unchanged side distribution. Glomerular filtration rate (GFR), measured with 99Tcm-DTPA, in the affected kidney decreased in Group 1 from 26 +/- 16 ml min-1 to 11 +/- 12 ml min1 (P < 0.0005), while GFR was unchanged in the affected kidney in Group 2, 26 +/- 13 ml min-1 versus 29 +/- 13 ml min-1. Extraction ratios of PAH and 51Cr-EDTA for the affected kidney in Group 1 decreased from 80 +/- 18 to 73 +/- 21% (P < 0.05) and from 16 +/- 5 to 7 +/- 5% (P < 0.005), respectively, while in Group 2 the PAH extraction ratio was not significantly changed, 86 +/- 5 versus 81 +/- 14%, but the 51Cr-EDTA extraction ratio for the affected kidney also decreased from 16 +/- 3 to 8 +/- 4% (P < 0.005). All patients had lateralization of renal vein renin to the affected kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Apolipoprotein-B-containing lipoproteins and the progression of renal insufficiency.

Hyperlipidemia is associated with accelerated glomerular sclerosis in experimental renal insufficiency. To investigate whether the dyslipoproteinemia seen in human renal failure also influences the future course of renal insufficiency, we have correlated plasma levels of lipids and apolipoproteins at start of follow-up with the subsequent change in renal function in 34 adult patients with chronic renal disease. Nineteen patients had primary renal disease, and 15 patients had diabetic nephropathy. Except for antihypertensive therapy no specific treatment to modify the progression of the disease was given during the follow-up. The rate of progression was determined by repeated measurements of the glomerular filtration rate (GFR). The time of follow-up ranged from 12 to 91 months with an average of 39.7 +/- 16.7 months. The mean initial GFR was 34.7 +/- 13.9 ml/min x 1.73 m2 body surface area and the average decline in renal function was -0.27 +/- 0.26 ml/min/month. The entry levels of triglycerides (TG; p = 0.04), very-low-density lipoprotein cholesterol (p = 0.03), apolipoprotein-B (ApoB; p = 0.008) and systolic blood pressure (SBP; p = 0.04) were significantly correlated with the rate of progression. Among lipoprotein variables, ApoB showed the strongest correlation with the decline in GFR. Patients with a progressive course of their disease also tended to have initially higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (NS), whereas the initial plasma concentration of high-density lipoprotein cholesterol did not show an association with the progression of renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗