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Biomedical subjects

A Leth

Publications and source records attributed to A Leth.

At least 19 recordsLinked to original sources

[Intensive dietary advice for patients with severe hypercholesterolemia].

Screening in general practice revealed a total of 124 patients (71 men and 53 women) with severe hypercholesterolaemia, defined as serum cholesterol levels over the 95th percentile for sex and age. The average serum cholesterol was 9.3 mmol/l with a maximal value of 15.5 mmol/l. On the basis of a dietary history for 48 hours and a dietetic interview, a dietician undertook a dietary analysis with the help of a computer programme (DANKOST) before and after dietary alterations for one and three months. The aims were normal body weight, cholesterol intake of under 200 mg/day, ratio between saturated and unsaturated fat between 1.0 and 1.8 and a roughage content of 26-30 g/day. A total of 61 patients completed the recommended dietary alterations. Alcohol intake was significantly higher in men and constituted more than 8% of the energy intake in 43 patients. Serum cholesterol was reduced by a total of 15.3%, triglyceride by nearly 20% while high density lipoprotein remained unchanged. The maximal decrease in serum cholesterol was 43%. In patients who adhered to the dietary changes, the average decrease was over 20%. Patients with hypertension and patients with serum cholesterol levels greater than or equal to 9 mmol/l showed greater decreases than the group as a whole. On the basis of the dietary interview, it did not prove possible to predict which patients would stick to the dietary restrictions.

Adult

[Treatment of severe primary hypercholesterolemia with lovastatin (Mevacor). A new therapeutic principle].

An open clinical trial comprising 59 outpatients with severe hypercholesterolemia (including 35 patients with familial hypercholesterolaemia) and considerable predisposition to ischaemic cardiac disease revealed a dosage-related pronounced effect of lovastatin on serum cholesterol and subfractions of this. After dietary regulation for a period of four months, a decrease in serum cholesterol of 11.7% was observed and after further treatment for six months with lovastatin with an average dose of 59 mg per 24 hours, the serum cholesterol decreased with a total of 45% of original value. Low density lipoprotein (LDL)-cholesterol decreased 44% and high density lipoprotein (HDL)-cholesterol increased by over 21%. Serum triglyceride fell by 20%. The serum-cholesterol/HDL-cholesterol ratio was reduced from 8.8 to 4.9. Only slight and transient subjective side-effects were observed and none of the patients dropped out of the trial for this reason. One patient with recognized ischaemic heart disease died from myocardial infarction. A tendency towards increasing liver parameters and creatin kinase was observed in the group as a whole but was not significant.

Adult

[Recommendations for clinical-chemical departments: lipid-lipoprotein analysis].

The section for preventive cardiology within the Danish Society for Cardiology has established a lipid group with representatives from The Danish Society for Clinical Chemistry, The Danish Society for Internal Medicine, The Danish Society for Cardiology, The Danish Society of Hypertension, The Danish College of General Practitioners, and The Danish Paediatric Society. The lipid group has elaborated recommendations for clinical chemical departments regarding lipid and lipoprotein analyses. The group suggests that doctors ordering lipid and lipoprotein analyses are offered the following: S-Cholesterol (total), substance conc., (fPt)S-Triglycerides, substance conc., S-HDL-cholesterol, substance conc., and (fPt)S-LDL-cholesterol, substance conc. (calculated). It is recommended that the biological variation be minimized by sampling in a sitting position after a 15 minutes' rest and by basing the clinical decision on a minimum of 2-3 determinations with an interval of about one month. The analytical variations should be reduced to below 3% (calculated as the variation coefficient), and it is recommended that laboratories participate in external quality control systems at least four times annually by reporting at least two human reference materials with different concentrations. As the use of reference intervals dependent on age and sex, based on random samplings of the background population, are less informative, it is recommended to refer to cutoff values for the clinical decision. The following cutoff values are recommended: S-Cholesterol (total), substance conc.: 6 mmol/l, (fPt)S-Triglycerides, substance conc.; 2.5 mmol/l, S-HDL-cholesterol, substance conc.: 0.9 mmol/l (fPt)-LDL-cholesterol, substance conc. (calculated): 4.5 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemistry, Clinical

Diurnal monitoring of blood pressure and the renin-angiotensin system in hypertensive patients on long-term angiotensin converting enzyme inhibition.

The temporal blood pressure course and the diurnal profile of the renin-angiotensin system were examined in 13 patients with essential hypertension receiving hydrochlorothiazide and enalapril once daily. Blood samples were taken and blood pressure was measured before the habitual morning dose of hydrochlorothiazide and enalapril (at 8.00 a.m.) and at seven time points over the next 24 h. During the period of maximal effect of enalapril (from 11.00 a.m. to 2.00 p.m.), the increase in plasma renin concentration ranged from no change to an 800% increase. A negative correlation was observed between an increase in plasma renin and a decrease in immunoreactive plasma angiotensin II concentration (Spearman rank-order correlation coefficient = 0.83). Notably, the greatest changes in plasma renin and angiotensin II concentrations after enalapril were seen in those patients whose blood pressure fell most during the day. We conclude that hypertensive patients on long-term therapy with enalapril once daily vary widely in their between-dose biochemical response to the drug, and that there is a significant association between the responsiveness of the plasma renin-angiotensin system and the effect on 24 h blood pressure.

Angiotensin-Converting Enzyme Inhibitors

Normal renal tubular response to changes of sodium intake in hypertensive man.

In a comparative study the influence of changes in dietary sodium intake on blood pressure, renal function, extracellular fluid volume, the renin-angiotensin-aldosterone system and plasma concentrations of arginine vasopressin, atrial natriuretic factor and cyclic guanosine monophosphate (GMP) was investigated in 12 patients with essential hypertension and in 10 normotensive controls. The subjects were studied after 4 days on a low (50 mmol/day), medium (180 mmol/day) or high (380 mmol/day) sodium intake. Renal sodium handling was assessed by simultaneous measurements of 51Cr-ethylenediaminetetraacetic acid (EDTA), lithium and sodium clearances. Identical values for the extracellular fluid volume, glomerular filtration rate and proximal and distal tubular resorption rates of sodium and water were found in the hypertensive patients and the controls at all three levels of sodium intake. In both groups, raising the sodium intake from low to high significantly increased 51Cr-EDTA and lithium clearance (an indirect measure of end-proximal fluid delivery), with intermediate values for the medium-sodium diet. The estimated values of fractional proximal and distal sodium resorption decreased when sodium intake was raised; the absolute proximal sodium resorption rate did not change, whereas the absolute distal sodium resorption rate as well as the extracellular fluid volume and sodium clearance increased. Blood pressure and the heart rate were unaffected by sodium intake. In both hypertensives and controls, plasma concentrations of active renin, angiotensin II and aldosterone decreased with increasing sodium intake, arginine vasopressin did not change, and atrial natriuretic factor and cyclic GMP increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Changed cyclic guanosine monophosphate atrial natriuretic factor relationship in hypertensive man.

Plasma concentrations of atrial natriuretic factor (ANF) and cyclic guanosine monophosphate (cGMP) were measured in 10 patients with essential hypertension and 10 normotensive controls on the fifth day of a low (50 mmol/day), a medium (180 mmol/day) and a high (380 mmol/day) dietary sodium intake. Plasma ANF and cGMP concentrations were less on the low than on the high sodium intake. Values for ANF on the medium sodium intake were intermediate. In normotensive subjects cGMP concentrations did not differ significantly on the low and the medium sodium intake. As compared with the controls plasma concentrations of cGMP were significantly increased in hypertensive patients on all three levels of sodium intake, while ANF concentrations were identical in the two groups. Since cGMP is a second messenger to ANF the data suggest an increased cellular response to ANF in patients with essential hypertension.

Adult

Iliac crest biopsy in longitudinal therapeutic trials of osteoporosis.

Changes in tetracycline-labelled iliac crest biopsies taken before and after 1 year of treatment with nandrolone decanoate + calcium, 17 beta-estradiol + norethisterone acetate + calcium or placebo were compared with changes in plasma bone Gla protein (pBGP), serum alkaline phosphatase (sAP), whole body retention (WBR) of Technetium-99m-diphosphonate [( 99mTc]DP) and bone mineral content (BMC) of the forearm. Based on a comparison between biopsy and noninvasive results, as well as on evaluation of the variation in the groups, certain guidelines for the use of bone histomorphometry in longitudinal therapeutic trials are suggested. It is proposed that bone biopsy is not used to monitor changes in amount of bone and that evaluation of changes in biopsy evaluated bone turnover is only attempted when the groups are large.

Aged

Bone turnover in spinal osteoporosis.

We have investigated biochemical indices of bone formation and bone resorption: serum alkaline phosphatase (sAP) plasma bone Gla protein (pBGP), fasting urinary hydroxyproline corrected for creatinine (FuHP/Cr), and fasting urinary calcium corrected for creatinine (FuCa/Cr) in 43 postmenopausal women with spinal fractures. Furthermore, histomorphometric indices of bone resorption and bone formation, as well as whole body retention (WBR) of 99m-technetium-diphosphonate (99mTc-DP), were determined. The results are compared to pre- and postmenopausal normal subjects. The results showed that indices of bone formation were mutually correlated except for sAP vs. WBR. sAP, WBR, and pBGP increased with age. sAP and WBR were not different between osteoporotics and age-matched controls, while pBGP and probably histological indices of bone formation were lower in osteoporotics than in age-matched controls. pBGP--and to a lesser extent sAP--were significantly correlated with all histological parameters reflecting bone formation. Finally, biochemical indices of bone resorption were high in osteoporotic patients and poorly correlated with histological bone resorption. The discrepancy between biochemical markers of bone formation may be related to the low sensitivity of sAP and WBR. Conversely, pBGP, sAP, and WBR may reflect different aspects of osteoblastic activity and bone mineralization. Finally, our data suggest that bone turnover increases with aging and that osteoporotic patients have higher bone resorption and probably lower bone formation than age-matched controls.

Adult

One year antihypertensive treatment with enalapril once daily: clinical and biochemical effects.

The purpose of the study was to evaluate the antihypertensive effect of enalapril administered once daily (q.d.), and to assess the effectiveness of enalapril in achieving sustained blockade of the renin-angiotensin system. The study population comprised 15 patients with uncomplicated, moderate essential hypertension whose blood pressure (BP) was not adequately controlled on hydrochlorothiazide (HCTZ) monotherapy. Enalapril 10-40 mg q.d. produced a significant fall in supine and erect BP (24 h after enalapril) that persisted during 1 year of combination therapy with HCTZ and enalapril. Blood pressure 6 h after enalapril was significantly lower than BP measured 24 h after enalapril, and occasionally at hypotensive levels. Plasma angiotensin II concentration fell significantly after enalapril with reciprocal increases in the plasma concentrations of renin and angiotensin I. The blockade of the renin-angiotensin system was maintained throughout the study. Bradykinin could not be detected in venous blood at any time during the study. We conclude that combination therapy with HCTZ and enalapril once daily is a rational, simple, and effective treatment in patients with moderate essential hypertension.

Adult

Effects of combined therapy with amiloride and hydrochlorothiazide on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in hypertensive patients.

After a run-in period of 8 weeks on a regimen of hydrochlorothiazide (HCT, median dosage 75 mg/day), patients with essential hypertension were randomly allocated to continued hydrochlorothiazide therapy (Group I) or additional treatment with amiloride (Group II, median dosage 15 mg/day, or 5 mg per 25 mg hydrochlorothiazide) for the following 12 weeks. Thereafter all the patients were changed to treatment with a fixed combination tablet containing 5 mg amiloride and 50 mg hydrochlorothiazide (Moduretic), keeping the thiazide dosage unchanged for an additional 12 weeks. In Group I patients there was no change in plasma potassium, total body potassium content or the renin-angiotensin-aldosterone system during the 12 weeks on HCT. When the treatment was changed to Moduretic, significant increases were found of 10% in plasma potassium and 3% in total body potassium content. No important stimulation of the renin-angiotensin-aldosterone system was found. In Group II patients addition of an average of 15 mg amiloride to the hydrochlorothiazide treatment led to significant increases in plasma potassium and total body potassium content of approximately 15% and 4%, respectively. There was also a significant increase in the plasma concentrations of renin, angiotensin II and aldosterone. Reducing the average dose of amiloride to 7.5 mg/day by use of Moduretic did not lead to decrease in plasma potassium or total body potassium content. Plasma concentrations of renin, angiotensin II, and aldosterone were decreased, but the individual changes varied markedly and no significant overall change was found.

Adult

Converting enzyme inhibition in mild and moderate essential hypertension. II.

In 24 patients with mild/moderate essential hypertension, we studied the effects of captopril with/without hydrochlorothiazide (Htz) on blood pressure, the renin-angiotensin system, blood bradykinin concentration (BBK), plasma volume, exchangeable sodium and glomerular filtration. Daily captopril doses of 75 and 150 mg were equally effective in reducing the blood pressure. Addition of Htz caused further blood pressure reductions. Nineteen patients attained a diastolic blood pressure less than or equal to 90 mmHg. Angiotensin converting enzyme inhibition with captopril led to a fall in plasma concentrations of angiotensin II (PAII) and renin substrate, and an increase in plasma concentrations of renin and angiotensin I. Patients starting with Htz had a higher PAII and subsequently a larger fall in blood pressure on captopril than untreated patients. BBK remained unchanged, indicating that the hypotensive action of captopril does not involve an accumulation of circulating kinin. Body fluid volumes and renal function were not affected by the various treatment regimens.

Adult

Treatment of renovascular hypertension by unilateral nephrectomy. A follow-up study in patients above 60 years of age.

The long term results of surgical intervention in 26 elderly patients with renovascular hypertension are presented. All patients were above 60 years of age at the day of operation. The majority of the patients had atherosclerotic renovascular disease with only one case of fibromuscular dysplasia. Several patients had severe extrarenal atherosclerotic disease. The diagnosis of renovascular hypertension was based upon the results of isotope renography, renal arteriography and renal vein catheterization. All patients underwent unilateral nephrectomy. Notably, no deaths or complications occurred in relation to surgery. At the follow-up study, blood pressure was lowered and the requirement for antihypertensive drugs reduced in 86% of the patients. We conclude that unilateral nephrectomy in elderly high risk patients with renovascular hypertension is a safe and efficient procedure.

Aged

Converting enzyme inhibition in mild and moderate essential hypertension. I. Acute effects on blood pressure, the renin-angiotensin system and blood bradykinin after a single dose of captopril.

The acute effects of 25 mg captopril on blood pressure, heart rate, components of the renin-angiotensin system and blood concentration of bradykinin were followed in a single-blind placebo study of untreated (group A, n = 15) and thiazide-treated (group B, n = 13) patients with mild or moderate essential hypertension. A drug-related fall in blood pressure was seen in both groups. The blood pressure reduction was more marked in group B than in group A. Heart rate remained unchanged. Plasma concentrations of angiotensin II decreased significantly with concurrent increases in plasma concentrations of renin and angiotensin I, indicating the in vivo inhibition of converting enzyme. Blood concentrations of bradykinin showed no systemic changes. The magnitude of blood pressure reduction was correlated both with the pretreatment levels and the concurrent decreases in plasma angiotensin II. Inhibition of angiotensin II formation can explain a large part of the acute hypotensive pharmacological action of captopril. Other vasoactive systems may be involved. The kallikrein-kinin system does not appear to participate as indicated by the unchanged concentrations of kinin in blood.

Adult

Progressive muscular dystrophy in Denmark. Natural history, prevalence and incidence.

Prevalence of progressive muscular dystrophy in 1965 and incidence in Denmark for the period 1965 to 1975 was studied by collection of data from hospital departments, nursery homes and general practitioners. This material was supplemented with information from death certificates and disablement pension records. Total patient group included 445 patients with progressive muscular dystrophy alive January 1st 1965. Prevalence was 69.4 per 10(6) male inhabitants in the Duchenne type, whereas the prevalences in the limb-girdle and facioscapulohumeral types were 36.5 and 18.6 per 10(6) inhabitants, respectively. Incidence was 222 per 10(6) male newborns in the Duchenne type, 66 and 26 per 10(6) newborns for the limb-girdle and the facioscapulohumeral types, respectively. Figures for the Duchenne type are in agreement with previous results. Both prevalence and incidence rates for the limb-girdle and the facioscapulohumeral types exceed published figures by a factor 3 to 6. These high Danish rates seem to reflect the true prevalence and incidence in the less serious types of progressive muscular dystrophy, probably because the Danish health system with free medical care and easy access to specialized hospital departments makes it possible to identify all cases of progressive muscular dystrophy.

Adolescent

Changes in blood pressure, fluid volumes and glomerular filtration rate during long-term treatment with prizidilol, an antihypertensive drug with combined vasodilatator and beta-adrenoceptor blocking actions.

The long term effects on blood pressure, body fluid volumes, glomerular filtration rate and plasma renin concentration were studied in 11 patients with essential hypertension during treatment with prizidilol, which is an antihypertensive compound with combined vasodilatator and beta-adrenoceptor blocking actions. After the patients had been treated for four weeks with placebo, the active treatment was given for 12 weeks. Prizidilol reduced both supine and erect blood pressure by 26/14 mmHg (p less than 0.01) and 24/16 mmHg (p less than 0.01) respectively, without inducing significant changes in heart rate. Plasma volume increased significantly by eight percent (p less than 0.02), whereas the increase in extracellular fluid volume was insignificant. Glomerular filtration rate decreased by 4 ml/min./1.73 m2 (p less than 0.02). Plasma renin concentration was unchanged. Prizidilol was tolerated well, but six patients developed oedema and gained weight, which necessitated addition of diuretics in three patients.

Adrenergic beta-Antagonists

The renin-angiotensin system during converting enzyme inhibition with captopril in patients with severe treatment-resistant hypertension.

The effect of captopril on blood pressure (BP) and various components of the renin-angiotensin system was assessed in ten severely hypertensive patients. Captopril acutely reduced the BP with a maximum decrease of 23% at 90-120 min. Maintenance treatment with captopril alone could not control the BP in any of the patients. Addition of hydrochlorothiazide markedly reduced the BP, while supplementation with propranolol caused no consistent changes. Three patients attained a supine diastolic blood pressure (SDBP) less than or equal to 90 mmHg. Only two patients had a fall in SDBP less than 10 mmHg. One patient stopped because of taste disturbances. Monitoring the renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased levels of angiotensin I and renin, indicating the inhibition of converting enzyme activity. Plasma concentration of renin substrate decreased significantly. This observation has important implications for the methodology of renin assays. Captopril is an effective alternative in the treatment of hypertensive patients not readily controlled with conventional therapy.

Adult