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Biomedical subjects

K Metsärinne

Publications and source records attributed to K Metsärinne.

29 records · Page 2Linked to original sources

Plasma level of atrial natriuretic peptide as an indicator of increased cardiac load in uremic patients.

Plasma levels of atrial natriuretic peptide (ANP) were measured by radioimmunoassay in 43 non-dialyzed uremic patients at rest and during maximal exercise to assess the possible relationship between plasma ANP levels and cardiac function, as judged by M-mode echocardiography and exercise tolerance. Patients with poor exercise capacity (exercise time less than 6 min) on dynamic exercise test had decreased left ventricular ejection fraction, increased left atrial diameter, and increased left ventricular mass index (LVMI), compared with patients with better exercise capacity (exercise time greater than 6 min). Plasma ANP was significantly higher in patients with poor exercise capacity and impaired cardiac function (202 pg/ml [95% confidence interval 119 to 284] at rest and 227 pg/ml [149 to 304] during exercise), compared with patients with better exercise capacity (75 pg/ml [50 to 102], p less than 0.005, and 123 pg/ml [80 to 167], p less than 0.05, respectively). Plasma ANP increased significantly (p less than 0.005) during exercise only in patients with better cardiac function. The best correlation among the variables studied was found between LVMI and plasma ANP concentration at rest (r = 0.56, p less than 0.001) and during exercise (r = 0.51, p less than 0.005), whereas neither blood pressure nor renal function showed any significant correlation with ANP levels. We conclude that plasma ANP levels are elevated in uremic patients with impaired cardiac function, correlating with increased LVMI. Plasma ANP determinations are useful in identifying increased cardiac load and consequent cardiac hypertrophy and dysfunction with known associations with increased cardiovascular mortality in patients with chronic renal failure.

Adult↗

Renin substrate in human amniotic fluid.

Purified human amniotic fluid renin substrate (RS) was compared to purified plasma RS. RS in plasma and amniotic fluid were similar in molecular weight, isoelectric point and immunological properties. Immunoreactivity of radio-iodinated amniotic fluid RS was lower than that of plasma RS. Measured by direct radioimmunoassay, RS-levels were only 10-22% of those obtained with indirect assay in 22 amniotic fluid samples. This difference suggests that amniotic fluid RS is less immunoreactive than plasma RS, possibly due to biochemical alteration or complex formation. No such difference in immunoreactivity was noticed in RS of decidual and placental cytosolic fraction.

Amniotic Fluid↗

No effect of short term angiotensin II infusion on plasma renin substrate levels in man.

We studied the effect of angiotensin II (A-II) infusion (4 ng/kg BW.min) on plasma renin substrate (RS) levels and PRA in five normal men during normal, diuretic-stimulated, and enalapril-interrupted function of the renin-angiotensin system. A-II infusion increased (15-25%) both systolic and diastolic blood pressure in the normal state and during angiotensin-converting enzyme inhibition, whereas the increase during diuretic-stimulated renin-angiotensin system function was less. The plasma RS concentration was measured by both direct and indirect RIA. The mean basal plasma RS levels, measured with direct assay, were 1516 +/- 150 (SE) in the normal state, 1566 +/- 150 after diuretic administration, and 1650 +/- 133 nmol/L after enalapril administration. The corresponding mean basal plasma RS levels measured with the indirect assay were 1073 +/- 100, 1031 +/- 57, and 902 +/- 78 nmol/L, respectively. Plasma RS levels did not change during or after the A-II infusions, whereas PRA decreased significantly in all experimental conditions. The results suggest that A-II exerts no direct stimulatory effect on hepatic release of RS. Thus, A-II appears not to be important in the short term regulation of plasma RS levels.

Adult↗

Increased levels of immunoreactive plasma renin substrate during infectious peritonitis in patients on continuous ambulatory peritoneal dialysis.

1. Renin substrate (RS) and certain serine protease inhibitors share structural homology. Previous studies have shown that RS may be an acute-phase protein. 2. This prospective study was carried out to monitor plasma RS and other components of the renin-angiotensin system and acute-phase proteins during infectious peritonitis in patients on continuous ambulatory peritoneal dialysis. 3. RS was measured by both an enzymatic assay and a direct radioimmunoassay. An enzymatic assay measures intact RS only, whereas a direct radioimmunoassay measures both intact RS, capable of releasing angiotensin I and des-(angiotensin I)-RS, the residue of RS after cleavage of angiotensin I. 4. RS determined by direct radioimmunoassay increased (P less than 0.001) during acute inflammation (peritonitis), whereas neither RS measured enzymatically nor plasma renin activity changed significantly. 5. Our observation points to RS being an acute-phase protein in man. 6. Serum angiotensin-converting enzyme was measured by both an enzymatic and an inhibitor-binding assay. Both assays showed decreased levels of angiotensin-converting enzyme during acute inflammation.

Acute-Phase Proteins↗

Effect of exercise on plasma renin substrate.

Effects of physical exercise on plasma renin substrate (RS) and plasma renin activity (PRA) levels were studied during short-term and prolonged exercise. Six healthy male volunteers performed a dynamic exercise test with exercise levels of 50, 100, 150, and 200 W for 4 min at each level. Measured with direct radioimmunoassay (RIA), which measures both intact RS and des-angiotensin I-RS (des-A I-RS), a significant increase in RS was seen during short-term exercise. RS measured with indirect (enzymatic) assay, which measures intact RS only, did not change, whereas PRA increased significantly. During prolonged exercise, a 75-km cross-country ski race, PRA increased more than two fold in ten healthy males participating in the study. Measured with direct RIA, RS increased by 22%, the corresponding increase in RS measured enzymatically was 10%. The increases in RS were not significant, however. It is concluded that the increased consumption of RS by rising PRA during exercise is counterbalanced by increased synthesis or release of RS by the liver or extrahepatic tissue. During prolonged exercise, liver production rate of RS apparently reaches a plateau which can be sustained for at least 7-8 h.

Angiotensinogen↗

Direct radio-immunoassay of renin substrate: effect of converting enzyme inhibition.

A direct radio-immunoassay (RIA) for renin substrate (RS) was compared to the enzymatic (indirect) assay, which measures intact RS only, whereas a direct assay measures both intact RS and des-angiotensin I-RS. In normal subjects, a significant, albeit weak, correlation between the methods was noticed. In hypertensive patients with different levels of plasma renin activity (PRA), RS concentration measured by both assays increased with increasing PRA, and for patients with PRA greater than 10 micrograms AI/l/h, the direct assay gave significantly higher RS values (55%), compared to the enzymatic assay. This indicates consumption of RS by increasing plasma renin and increasing production rate of RS with increasing PRA, of potential importance in the pathogenesis of hypertension. In 11 patients with renovascular hypertension, treatment with the angiotensin-converting enzyme (ACE) inhibitor, lisinopril, resulted in a significant increase in PRA, accompanied by a decrease in RS measured by the enzymatic assay. Lowered plasma RS concentration, by reduction of the velocity of the renin-RS reaction, will distort and invalidate results of PRA determination during treatment with ACE inhibitory compounds. No change in RS measured by direct RIA was noticed, however. The results suggest that ACE inhibition may not have an effect upon RS production and that its effect on plasma RS is limited to a reduction of intact RS measured by the enzymatic assay.

Angiotensin I↗

Plasma atrial natriuretic peptide in cardiac disease and during infusion in healthy volunteers.

Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) were low or undetectable in 8 healthy subjects and 9 control patients without cardiac disease, and raised in 17 patients with congestive heart failure (CHF). Highest concentrations were measured in patients with severe CHF. High plasma ANP levels were also found in 2 patients with paroxysmal supraventricular tachycardia and associated transient polyuria. Infusion of synthetic human alpha-ANP, 110-125 micrograms over 30 min, to 3 healthy males resulted in a 2.3-fold increase in natriuresis and diuresis but had no effect on kaliuresis. Plasma levels of renin activity, aldosterone, and antidiuretic hormone did not change significantly. ANP infusion gave plasma ANP levels of the same magnitude as those found in severe CHF; levels returned to baseline within 15 min of stopping the infusion. Thus ANP appears to be a circulating hormone in man, at least in severe CHF and supraventricular tachycardia.

Adult↗

Value of electron microscopy in kidney biopsy diagnosis.

Kidney biopsy reports given during 2003 were collected from the authors' pathology database. A total of 111 biopsies were performed. Five tumor samples were not studied with electron microscopy (EM). Of the remaining 106 biopsies, 85 were studied with EM. EM was not performed in 10/24 transplant biopsies, or in 11/82 cases of suspected primary kidney disease. The role of EM was evaluated by grouping the samples in 3 categories: (1) EM was essential for diagnosis, (2) EM contributed to the interpretation and cleared uncertainties, and (3) EM had no influence on the diagnostic process. In transplant biopsies EM influenced the final diagnosis in 86% of cases (category 2). In biopsies performed for primary kidney disease EM was essential for diagnosis in 18.3% clearly contributed in 53.5%, and had no influence on the final diagnosis in 28.2% of cases. The study suggests that the importance of EM has not decreased during the last few years. Because only about 25% of the EM reports did not have any influence on the diagnostic process, it is recommended that kidney biopsy protocols should include EM in all biopsy cases, or at least tissue should be reserved for EM studies of all cases. Because of the influence of EM on the diagnostic process the need for EM in pathology training should be emphasized.

Adult↗

Ochronosis: a report of a case and a review of literature.

A patient with alkaptonuria and ochronotic pigment deposited in articular cartilage and sclerae clinically manifested a serious osteoarthritis of the peripheral and axial joints and synchondrosis, typically involved in long lasting cases of this hereditary defect of homogentisic acid oxidase. This is the first patient with this disorder reported, where a non-cemented total knee prosthesis (PCAR) was applied on both knees. This was possible due to the good quality of the bone stock, which did not seem to be impaired by ochronosis. Our patient had no cardiac symptoms or murmurs, but had a slight calcification in the annulus of aorta observed with echocardiography, a useful new method for screening this disease manifestation. A third new aspect reported is the immunopathology of the synovial tissue. Small pieces of torn-off cartilage were seen embedded in the synovial stroma. This was associated with a slight hyperplasia of the C3bi-receptor positive and proline hydroxylase positive type A and B synovial lining cells. Perivenular infiltrates contained CD2 positive T lymphocytes, mostly belonging to the CD4 subset, and some C3bi-receptor positive monocytes. Activated CD25 positive and immunoglobulin light chain positive T and B lymphocytes were absent or few. Because modern medicine has much to offer to those suffering from this ancient inborn error of metabolism in the form of new specific diagnostic methods and new surgical modes of treatment, such as endoprosthesis surgery and cardiac valve replacement, we also present a literature overview of this interesting condition.

Dioxygenases↗

Increased plasma angiotensinogen in cardiac transplantation patients.

OBJECTIVES: Interleukin 6 (IL-6) stimulates the production of angiotensinogen (renin substrate, RS), an acute phase reactant and the precursor of the potent vasoconstrictor angiotensin II. This study assesses the effect of cardiac transplantation on plasma levels of angiotensinogen and interleukin 6. METHODS: Effects of cardiac transplantation on plasma levels of renin substrate and IL-6 were studied in twelve patients with NYHA IV end-stage heart failure. Renin substrate, IL-6, plasma renin activity, C-reactive protein and serum amyloid A were determined 1 day before cardiac transplantation, and 1 day, 1 week, 4 weeks and 12 weeks postoperatively. Renin substrate was measured by both direct and indirect radioimmunoassay. An indirect assay measures intact renin substrate only, capable of releasing angiotensin I, while a direct assay measures both intact renin substrate and des-angiotensin I-renin substrate, the residue of renin substrate after cleavage of angiotensin I. RESULTS: Plasma renin substrate and IL-6 increased significantly on day 1 as compared with preoperative levels. Plasma renin substrate increased (measured by direct and indirect assay) by 64 and 50%, respectively, IL-6 levels by 43%. Plasma IL-6 returned to preoperative (normal) levels by 4-12 weeks. Plasma renin substrate levels remained elevated for the follow-up period of 12 weeks. The direct assay always gave higher values than the indirect assay, presumably due to consumption of renin substrate by renin. Consequently, a negative correlation between plasma renin activity and renin substrate measured with indirect assay was observed. CONCLUSIONS: Our findings suggest that cardiac transplantation brings about an acute phase reaction, mediated partly by IL-6, with increased synthesis of acute phase proteins like renin substrate. This may result in increased angiotensin II levels. Considering the trophic effects of angiotensin II on vascular tissue, increased production of renin substrate may contribute to the development of proliferative cardiovascular changes in heart transplant recipients.

Adolescent↗