Neuroendocrine activation after myocardial infarction.
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Atrial Natriuretic Factor↗
Biomedical subjects
J Remes
Publications and source records attributed to J Remes.
Neurohormonal activation in patients with mild or moderately severe congestive heart failure and effects of ramipril. The Ramipril Trial Study Group.
OBJECTIVES: To describe neurohormonal activation in patients with mild or moderate heart failure and how it may be modified by treatment with ramipril. SETTING: Cardiology departments at 24 hospitals in Denmark, Finland, Norway, and Sweden. PATIENTS: 223 patients with mild or moderately severe congestive heart failure who were taking diuretics with or without digitalis. DESIGN: Randomised, double bind, multicentre, placebo controlled comparison of ramipril and placebo. Venous blood samples were drawn at rest, before blind treatment, and after 12 weeks of treatment with the study drug. A probability prediction score for mortality derived by stepwise linear discriminant from neurohormone data in the first cooperative north Scandinavian enalapril survival study (CONSENSUS I) was used to assess combined activity of the different neurohormonal systems. RESULTS: Plasma concentrations of atrial natriuretic peptide were raised at baseline but angiotensin II, aldosterone, and noradrenaline concentrations were within normal limits. There was, however, a wide interindividual variation. Plasma noradrenaline concentration and prediction score were higher among patients with class III congestive heart failure according to the New York Heart Association's classification than among patients with class II congestive heart failure (P < 0.05). There was a modest but significant inverse correlation between exercise duration at baseline and plasma noradrenaline concentration (r = -0.21, P = 0.0023), aldosterone concentration (r = -0.14, P = 0.04), and prediction score (r = -0.24, P = 0.0004). Prediction score at baseline was significantly higher among those who died (n = 10) than among survivors (P = 0.03). Angiotensin converting enzyme activity was suppressed and plasma concentrations of aldosterone and atrial natriuretic peptide were reduced after 12 weeks of treatment with ramipril compared with placebo. In patients with the most pronounced neurohormonal activation at baseline (highest third of noradrenaline concentration or prediction score), noradrenaline concentration and prediction score were significantly lower after 12 weeks of taking ramipril compared with placebo. Patients with a prediction score in the highest third at baseline had a higher heart rate than to those in the lowest third (P = 0.003). CONCLUSIONS: Neurohormonal activation is associated with the degree of symptoms and the severity of disease in mild or moderately severe congestive heart failure. Treatment with ramipril attenuates neurohormonal activation. This effect is most pronounced among patients with the highest circulating concentrations of neurohormones before the start of treatment.
Adult↗
Internalization of N-formyl peptide chemotactic receptor-ligand complex by human neutrophils. The role of the receptor's 2-kDa external domain and carbohydrates.
We treated human neutrophils with papain to remove the external 2-kDa domain and along with it the two oligosaccharide side chains of the N-formyl peptide chemotactic receptor and investigated what effect their absence has on the ligand-receptor complex internalization. After prelabeling of the cells with 125I-hexapeptide for 5 min at 22 degrees C, about 95% of the bound radioactivity was located on the cell surface. During the first 5-min incubation at 37 degrees C both the control and papain-treated cells internalized 73% of the receptor-ligand complexes suggesting that internalization is very rapid in human neutrophils and that removal of the external domain and the carbohydrates of the receptor does not affect the rate. However, the truncated receptor-ligand complexes were degraded at a faster rate because the radioactivity released into the medium was significantly higher and correspondingly the acid-resistant radioactivity significantly lower in the papain-treated neutrophils than in control cells already at 5 min and all subsequent time points. The radioactivity accumulated in the medium of the control and papain-treated neutrophils represented inactivated 125I-hexapeptide as less than 5% of it at 5, 30 and 120 min were capable of rebinding. No receptor recycling was detected in either cells. These results indicate that removal of the 2-kDa external domain and the carbohydrates of the N-formyl chemotactic receptors has little effect on the internalization rate of the receptor-ligand complexes but accelerates markedly their intracellular degradation.
Amino Acid Sequence↗
Incidence of heart failure in eastern Finland: a population-based surveillance study.
Heart failure is a frequent disorder, but there is little population-based data available on its incidence. We have studied the incidence of heart failure in 45-74-year-old inhabitants in four rural communities in eastern Finland (total population 37,600; 11,000 45-74 years of age). The aim was to identify all patients in whom symptoms had started and in whom a diagnosis of heart failure had been established during a 2-year study period. General physicians, working in community health centres in the study area, referred all their patients with suspected heart failure to the study. A register of drug reimbursement, hospital discharge and other health care registers were used to identify patients who had not been referred. The Boston criteria were used to verify the diagnosis. One hundred and thirteen subjects (51 men and 62 women) were enrolled, of whom 51 (38 men and 13 women) had definite heart failure. Age-adjusted incidence rate of heart failure (per 1000 . year-1) was 4.0 in men and 1.0 in women, and the incidence rates increased with age in both sexes. Coronary heart disease or hypertension was evident in 41 (80%) cases. The striking difference in the incidence rates between men and women is probably explained by the excessive occurrence of coronary heart disease among men in eastern Finland.
Age Factors↗
Relationship between hyperglycaemia and aerobic power in men with newly diagnosed type 2 (non insulin-dependent) diabetes.
The aim of the study described here was to evaluate aerobic function during exercise and its determinants in middle-aged men with newly diagnosed Type 2 (non insulin-dependent) diabetes. Using breath-by-breath technique, we measured O2 uptake at anaerobic (ventilatory) threshold and at peak exercise in a group of diabetic men (n = 19; fasting blood glucose 8.6 +/- 0.7 mmol l-1, mean +/- SEM) without any disease or medication that could have had an influence on exercise performance, and compared the results to those observed in non-diabetic healthy control men (n = 18). There were no differences in physical activity or smoking habits between the groups. Oxygen uptake was lower in the diabetic men than in the control men both at anaerobic threshold (15.0 +/- 0.8 vs. 18.8 +/- 1.0 ml min-1 kg-1, P < 0.01) and at peak exercise (25.3 +/- 1.5 vs. 31.1 +/- 1.4 ml min-1 kg-1, P < 0.01). In the diabetic men peak O2 uptake showed an inverse linear correlation with age (r = -0.71, P < or = 0.001), fasting blood glucose (r = -0.49, P < 0.05) and glucose response in an oral glucose tolerance test (r = -0.43, P < 0.05). In addition, long-term smoking was associated with impaired peak O2 uptake. In a stepwise multiple regression procedure 75% of the total variance of peak O2 uptake in the diabetic men was explained by age, post-load blood glucose response and smoking history. Thus, in addition to ageing and smoking, hyperglycaemia is correlated with impaired aerobic power in men with newly diagnosed Type 2 diabetes.
Adult↗
Covalent cross-linking of radiolabeled N-formylated hexapeptide to its specific receptor on rat and human neutrophils: evidence for a ligand induced complex formation.
The structure of the rat and human neutrophil receptor for N-formylated chemotactic peptides was characterized using 125I-labeled N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys hexapeptide as a ligand and an affinity cross-linking technique. 125I-hexapeptide bound to purified rat peritoneal neutrophils was time, temperature and pH-dependent. The average receptor number per cell was about 67,000 and dissociation constant (Kd) 0.41 nM. Formyl-MLLP, fMLP, fNLP, were 750%, 15%, 8.6% respectively and Boc-MLP, Boc-NLP, and MLP 0.6% as potent as the hexapeptide in inhibiting the binding of 125I-hexapeptide to rat neutrophils. The same correlation was found between these peptides in their potency to induce chemotaxis. This indicates that the rat neutrophil chemotactic receptor is like human receptor also a highly stereoselective and requires a N-formylated ligand for high affinity binding. Affinity cross-linking of 125I-hexapeptide to rat and human neutrophil chemotactic receptor with glutaraldehyde revealed on SDS-PAGE a 85-kDa and 62-kDa major complex and a 170-kDa and 120-kDa minor complex, respectively. The 120-kDa complex was absent in human neutrophils if the cells were treated with glutaraldehyde prior to cross-linking of 125I-hexapeptide to its receptor. Likewise, the larger complex was absent if neutrophils were exposed to heterologous ligand (C5a) prior to glutaraldehyde treatment and cross-linking of 125I-hexapeptide to its specific receptor. These results demonstrate that the rat neutrophils possess a functional high-affinity receptor for N-formylated chemotactic peptides and that the size of the monomeric receptor is 85-kDa and about 23-kDa larger than that of the human receptor. Upon homologous ligand binding the receptor seems to form a larger complex.
Amino Acid Sequence↗
Validity of clinical diagnosis of heart failure in primary health care.
Validity of heart failure (HF) diagnosis was studied in 88 patients (37 men and 51 women), aged 45-74 (mean 61) years, in whom HF diagnosis had been newly made by primary health care physicians. Boston criteria for HF and a supplementary classification, based on information from clinical examinations and a 6-month follow-up, were used to define HF diagnosis as 'definite', 'possible' or 'unlikely'. Twenty-eight (32%) patients (21 men and seven women) had 'definite' HF and 46 (52%) (28 men and 18 women) had either 'definite' or 'possible' HF by both classifications. In 30 (34%) patients (six men and 24 women) HF diagnosis was 'unlikely' by both classifications. In conclusion, false-positive diagnosis of HF was common in primary health care, and HF diagnosis was more difficult in women than in men. Obesity, unrecognized symptomatic myocardial ischaemia without HF and pulmonary diseases were the most important conditions leading to false-positive HF diagnosis.
Aged↗
Neuroendocrine activity in untreated heart failure.
Neuroendocrine activity was studied in 60 consecutive untreated patients with dyspnoea and a clinical suspicion of heart failure. On the basis of the so-called Boston clinical criteria the diagnosis of heart failure was regarded as unlikely in 26 patients, possible in 15 patients, and definite in 19 patients. These groups were studied before any drug treatment was started and were compared with a control group of 69 healthy individuals. Plasma atrial natriuretic peptide concentration was clearly raised in patients with definite heart failure and slightly raised in patients with possible heart failure. Plasma adrenaline concentration was somewhat raised in patients with definite or possible heart failure, whereas plasma noradrenaline concentration was raised only in patients with definite heart failure. Plasma renin activity was not increased in any of the patient groups and plasma aldosterone concentration was slightly increased only in patients with definite heart failure. In the total patient series there were significant correlations between plasma atrial natriuretic peptide concentration and markers of the severity of left ventricular dysfunction. There was some evidence of neuroendocrine activation in untreated heart failure: plasma concentrations of atrial natriuretic peptide and catecholamines were increased but the renin-angiotensin-aldosterone system showed little or no activation.
Aged↗
Usefulness of M-mode echocardiography in the diagnosis of heart failure.
The utility of M-mode echocardiography in the diagnosis of heart failure (HF) was evaluated in a study of 70 patients with suspected HF (26 men and 44 women) and 63 control persons (26 men and 37 women), all aged 45-74 years. The patients were classified according to the certainty of HF diagnosis using the Boston criteria: 27 patients were defined as 'unlikely' to have HF, 19 as having 'possible' HF, and 24 as having 'definite' HF. In calculations of the sensitivities and specificities for echocardiographic variables in detecting 'definite' HF, the 95% confidence limits in the control group were used as cut-off point values. Sensitivities thus attained were 91% for mitral valve E point-septal separation (EPSS), 73% for left ventricular (LV) fractional shortening (FS), and 64% for peak rate of increase of LV diameter (PLR), respectively, and the specificities were 73, 88, and 78%, respectively. When EPSS, FS and PLR were all normal, the likelihood of 'definite' HF was as low as 7%. We conclude that M-mode echocardiography is actually a useful method in the diagnostic evaluation of patients with suspected HF, and it is more reliable in excluding than confirming the presence of HF.
Aged↗
Effect of enalapril on plasma atrial natriuretic peptide in late recovery phase of acute myocardial infarction.
A 12 week randomised, double blind, placebo controlled study on the effect of enalapril (5-20 mg daily) on the concentration of plasma atrial natriuretic peptide level and activity of the sympathetic nervous system and renin angiotensin system was done on 27 patients who had suffered an uncomplicated acute myocardial infarction two to six months earlier. None of our patients needed drug treatment for heart failure, but their exercise capacity was markedly limited. Plasma neurohormone concentrations at baseline and after 12 weeks of treatment were also compared with those of healthy controls. Concentrations of plasma atrial natriuretic peptide concentrations remained high throughout the study in those patients on beta-blockers. Enalapril treatment had no definite effect on the concentrations of plasma atrial natriuretic peptide or other neurohormone.
Aldosterone↗
Cardiopulmonary exercise testing has limited value in diagnosing heart failure.
Usefulness of cardiopulmonary exercise testing in the diagnosis of heart failure was evaluated in a study of 59 patients with clinically suspected heart failure (22 men and 37 women) and 75 healthy control persons (34 men and 41 women), aged 45-74 years. Patients were classified according to certainty of the diagnosis by the Boston criteria: 27 patients were "unlikely" to have heart failure (group I), 19 had "possible" (group II) and 13 had "definite" heart failure (group III). Oxygen consumption at peak exercise and at the appearance of the ventilatory threshold was lower in group III than in the control group (15.6 +/- 1.5 versus 26.0 +/- 0.8 ml/min/kg, p less than 0.001 and 11.8 +/- 1.5 versus 18.0 +/- 0.4 ml/min/kg, p less than 0.001, respectively). However, the distribution of oxygen consumption values was wide in both the control and patient groups, and considerable overlapping of values between study groups was observed. Thus, cardiopulmonary exercise testing appeared to be of limited value in the diagnosis of heart failure.
Aged↗
Evaluation of heart size and pulmonary vasculature. Conventional chest roentgenography and image intensifier photofluorography compared.
Inter- and intraobserver variation and diagnostic accuracy in estimation of heart size and pulmonary vasculature were evaluated for conventional film-screen technique and image intensifier photofluorography. Interpretation of 218 p.a. and lateral chest films by both imaging techniques was performed independently by 4 readers. Heart size relative to body surface area measured from the plain chest films was used as the reference in cardiac size determination. Overall diagnostic accuracies of conventional radiography and image intensifier photofluorography for cardiomegaly were close to each other, 0.70 vs 0.68, respectively. Specificity of film-screen radiography was better than that of photofluorography (0.92 vs 0.84, p less than 0.05). Interobserver agreement was poor both in assessment of the heart size and pulmonary vasculature (range of kappa coefficients 0.18-0.59) while the intraobserver consistency (kappa coefficients 0.60-0.85) was good to excellent. The results suggest a limited usefulness of visual assessment of heart size and pulmonary vasculature in chest roentgenographs.
Aged↗
Clinical outcome and left ventricular function 23 years after acute coxsackie virus myopericarditis.
The clinical outcome of 18 patients, who presented with a Coxsackie virus myopericarditis in 1965, was evaluated 23 years later. Five patients had died, two of them had had heart failure. Thirteen patients and 23 healthy control subjects underwent exercise testing with gas exchange analysis. Left ventricular (LV) peak filling rate (PFR) was estimated by digitized M-mode echocardiography. Left ventricular ejection fraction was measured at rest and during exercise by radionuclide angiography. All patients were free of cardiac symptoms. Their clinical examination and the chest X-ray were normal. Peak oxygen consumption was not decreased in the patient group compared with the control group. PFR was significantly lower in the patient group than in the control group, 10.2 +/- 0.4 vs 13.2 +/- 0.4 cm s-1, P less than 0.001 (mean +/- SEM). LV ejection fraction was normal at rest in all patients (58 +/- 1%). An abnormal LV ejection fraction response to exercise was observed in two patients. Our data indicate that long-term prognosis after acute Coxsackie virus myopericarditis is good in a majority of patients.
Acute Disease↗
Enalapril in chronic heart failure, a double-blind placebo-controlled study.
The efficacy of enalapril, a new angiotensin-converting enzyme inhibitor, was investigated in a double-blind placebo-controlled study in 24 patients with chronic heart failure. The patients belonging to NYHA functional class II-IV and treated with digoxin and diuretics were randomized to enalapril (12 patients) or placebo (12 patients) treatment for a 12-week period. Assessments were carried out at baseline and at 4 and 12 weeks during the treatment period. Complete data could be obtained on 10 patients receiving enalapril and on 11 patients receiving placebo. NYHA functional class improved by at least one class in 6 of 10 patients in the enalapril group, but only in 1 of 11 patients in the placebo group (chi 2 = 6.54; p less than 0.05). Duration of bicycle ergometer exercise increased significantly in the enalapril group from 8.8 +/- 3.4 to 11.3 +/- 4.2 (4 weeks) and to 11.2 +/- 3.6 min (12 weeks; p less than 0.05 for both), whereas it remained unchanged in the placebo group. Left ventricular ejection fraction by radionuclide ventriculography in the enalapril group increased significantly (baseline: 33.5 +/- 19.9%, 4 weeks: 40.0 +/- 20.0% (p less than 0.001), 12 weeks: 39.6 +/- 20.1% (p less than 0.01], whereas in the placebo group it did not change significantly from the baseline of 48.8 +/- 16.7%. The results indicate that enalapril induces a sustained relief of symptoms and improves exercise capacity in patients with heart failure. This subjective improvement appears to be accompanied by an increase in ejection fraction.
Adult↗
Plasma catecholamines in Finnish sauna.
Plasma catecholamines were measured by a modified single-isotope radioenzymic assay in five healthy medical students during and after a Finnish sauna bath with or without previous beta-blockade. The plasma noradrenaline rose more than twofold after 10 min in the hot room (100 degrees C) while the plasma adrenaline content exhibited smaller increases. The plasma noradrenaline concentration remained elevated or further increased after 5 min in a cool swimming pool (22 degrees C) whereas the exposure to cool water restored the plasma adrenaline concentration to resting values. Plasma noradrenaline, but not adrenaline, was still markedly elevated after a rest period of 15 min after the cool pool. Oxprenolol (40 mg) given 30 min before the sauna did not alter the plasma catecholamine pattern although it effectively lowered the heart rate before, during, and after the exposure to the heat stress.
Adult↗
Residual marrow damage: possible explanation for idiosyncrasy to chloramphenicol.
The effect of oral administration of chloramphenicol was studied in normal mice and mice having residual marrow damage. In the concentration used the drug had no detectable effect on the marrow of normal mice but caused a progressive fall in the numbers of pluripotential stem cells and granulocytic progenitor cells in mice bearing residual marrow damage. However, cells taken from such mice were no more sensitive than normal cells to the in vitro action of chloramphenicol. The results suggest that unrecognized residual marrow damage can be an aetiological factor in marrow failure due to drug idiosyncrasy.
Anemia, Aplastic↗
A controlled trial of androgen therapy in experimental chronic hypoplastic marrow failure.
A controlled trial of an androgen, 17-nortestosterone decanoate, was carried out to test its effect as therapy in an experimental model of chronic hypoplastic marrow failure. No effect was detected.
Anemia, Aplastic↗
Five years of surgical experience with peritoneal dialysis.
In this study, we evaluate retrospectively five years experience with the Swann Neck Missouri DC catheters. Sixty three catheters are placed in 51 patients. The total observation period is 695.6 months and the average time is 13.6 months per patient. The last 21 catheters are coiled type. Infectious complications remain the most worrisome problem in peritoneal dialysis. Exit site infections are seen in 24%, tunnel infections in 8%, peritonitis in 38% and abdominal hernias in 16% of the patients. The results in our series (peritonitis every 29.0 patient-months) are in accordance with data from the literature. The combination of a good surgical technique and an efficient postoperative attendance have reduced this frequency. In the situation of a tunnel infection, surgical removal remains the treatment of choice. To prevent an exit site infection, the entry port must be well nursed and protected. A coexisting abdominal hernia can be repaired during the implantation procedure. Fourty six peritoneal dialysis catheters have been removed. Transplantation and death are the main reasons (59%).
Adolescent↗