[Hyperhomocysteinemia--a new risk factor for vascular diseases?].
Explore the source record for details and available documents.
Homocysteine↗
Biomedical subjects
B Israelsson
Publications and source records attributed to B Israelsson.
Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma.
The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma.
Adolescent↗
Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors.
Moderate hyperhomocysteinaemia is a frequent finding in atherothrombotic cerebrovascular disease. This study confirms and extends this observation. Hyperhomocysteinaemia was present in 57 of 142 survivors with stroke (40%) and in four of 66 controls (6%). Plasma homocysteine concentrations were increased not only in carotid artery disease or lucunar stroke but also in haemorrhagic or embolic strokes. Homocysteine values were unrelated to the presence of hypertension, smoking, or hypercholesterolaemia, or to the concentrations of blood glucose, glycosylated haemoglobin, and plasma fibrinogen. Multiple regression analysis of the patient data showed that about 40% of the variation in plasma homocysteine concentrations could be predicted by the values for the homocysteine metabolism cofactors, blood folate and plasma pyridoxal 5-phosphate and by renal function as reflected in the values for serum creatinine. In patients, urine excretion of homocysteine per unit creatinine was significantly increased and strongly correlated both to the plasma homocysteine concentration and to the values for blood folate, plasma pyridoxal 5-phosphate, and serum vitamin B12. We conclude that moderate hyperhomocysteinaemia is frequently present in cases of stroke, is independent of other stroke risk factors or the type of stroke, and is partly related to renal function and the concentrations of homocysteine metabolism cofactors.
Adult↗
Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status.
Homocysteine is a probably atherogenic amino acid, the fasting and post-methionine load serum concentrations of which have been reported to be much lower in premenopausal women than in men and postmenopausal women. This difference has been proposed to explain the reduced proneness of premenopausal women to vascular disease. We measured both free and total plasma homocysteine concentrations both fasting and post-methionine load, in 169 healthy subjects. Twelve subjects (7%) had distinctly abnormal plasma homocysteine values. Among the remaining 157 subjects, neither fasting nor post-load values of free or total homocysteine were lower in premenopausal women (n = 46) than in men of similar age (n = 41) or postmenopausal women (n = 37). Fasting but not post-load values were lower in postmenopausal women than in men of similar age (n = 33), and lower among the women as a whole (n = 83) than among the men (n = 74). In men, fasting values increased with age, and paralleled age-related decreases in the concentrations of homocysteine metabolism cofactors (serum vitamin B12, blood folate, and plasma pyridoxal 5-phosphate). Both in men and in women, fasting total plasma homocysteine values were significantly and negatively correlated to serum vitamin B12 and blood folate concentrations. Whether the small differences in plasma homocysteine values between the present men and women may be a contributory factor vis-à-vis their different proneness to vascular disease has yet to be settled.
Adult↗
Noninvasive quantification of atherosclerotic lesions. Reproducibility of ultrasonographic measurement of arterial wall thickness and plaque size.
A noninvasive method based on high-resolution B-mode ultrasonography and a computerized image-analyzing system were used for the quantification of early (thickening of the intima-media complex) and late (plaque) atherosclerosis in the carotid and the femoral artery. The difference between repeated measurements was assessed to estimate intraobserver and interobserver differences. The results were satisfactory, with a coefficient of variation for measurement of lumen diameter in the common carotid artery of 3.8 +/- 4.1% (r = 0.91) and for the femoral artery of 4.8 +/- 4.1% (r = 0.93). Corresponding figures for intima-media thickness in the common carotid artery and the femoral artery were 10.0 +/- 8.5% (r = 0.86) and 16.2 +/- 12.6% (r = 0.91), respectively. The coefficient of variation for measurements of maximal intima-media thickness at the site of the plaque was 14.6 +/- 10.5% (r = 0.88); for plaque base, 13.1 +/- 9.0% (r = 0.91); and for plaque area, 16.3 +/- 12.6% (r = 0.90). The method seems promising for the detection and quantification of early and late atherosclerotic lesions in the carotid and femoral arteries.
Aged↗
Elevated urinary excretion of beta-hexosaminidase in smokers.
The excretion of urinary beta-hexosaminidase in 203 apparently healthy males and females correlated significantly with their tobacco consumption (r = 0.26; p less than 0.001). Those who smoked more than 10 g tobacco per day excreted significantly more beta-hexosaminidase in urine than non-smokers, which indicates the presence of a low grade renal injury in smokers.
Creatinine↗
Influence of hydrolysis on plasma homocysteine determination in healthy subjects and patients with myocardial infarction.
After acid hydrolysis, mean plasma homocysteine concentrations, measured as homocysteine disulphides, of about 1000 and 40 mumol/l have recently been reported in 26 survivors of myocardial infarction and 26 matched control subjects, respectively. This finding contrasts sharply with those more than 50 times lower total homocysteine concentrations found by other research groups in non-hydrolysed plasma from survivors of myocardial infarction. Using the same hydrolysis conditions, we could not detect any homocysteine disulphides in plasma hydrolysates from 9 survivors of myocardial infarction and 10 healthy subjects, who had mean total homocysteine concentrations in non-hydrolysed plasma of 16.9 +/- 6.5 and 15.8 +/- 10.3 mumol/l, respectively. The chromatograms contained several peaks, probably representing peptides, which disappeared with more complete hydrolysis and which might have been misinterpreted as homocysteine disulphides in the reported study. Only after reduction of disulphides and by using a sulphydryl-selective extraction procedure were we able to determine mean homocysteine concentrations in hydrolysed plasma to be 26.2 +/- 7.9 mumol/l in the survivors of myocardial infarction and 24.5 +/- 12.2 mumol/l in the healthy reference subjects. Thus, we could not confirm that survivors of myocardial infarction have homocysteine concentrations that are many times higher than found in healthy subjects.
Adult↗
Atherosclerosis and acetaldehyde metabolism in blood.
Acetaldehyde elimination in blood homogenates and erythrocyte aldehyde dehydrogenase (ALDH) activity were studied in 64 patients operated before the age of 60 years because of symptomatic stenosis of aorta, iliac, or carotid arteries and in 38 healthy controls. The disappearance of acetaldehyde in blood homogenates was biphasic. Patients showed an enhanced elimination of acetaldehyde during the second phase (30-60 min), as compared to controls (T1/2 of acetaldehyde was 103 +/- 47 and 198 +/- 93 min, respectively, P less than 0.001). No correlation was found between ALDH activity and acetaldehyde elimination rate. Acetaldehyde elimination in blood homogenates and [14C]acetaldehyde binding to plasma proteins, hemoglobin, and erythrocyte membranes were studied in 10 patients with atherosclerotic disease and in 12 healthy controls. There was a significant correlation between unstable binding of [14C]acetaldehyde to plasma proteins and the half-life of acetaldehyde in the elimination test (p = 0.74, P less than 0.005). Fractionation of plasma proteins after incubation with [14C]acetaldehyde revealed no difference between patients and controls in the distribution of radioactivity. The binding of [14C]acetaldehyde to hemoglobin or erythrocyte membranes did not differ between patients and controls. These results indicate that patients with angiopathy and an enhanced acetaldehyde elimination in blood have reduced binding of acetaldehyde to plasma proteins. As unstable binding of acetaldehyde to proteins is known to involve free amino groups of amino acid residues, modification of these residues in atherosclerotic disease is conceivable.
Acetaldehyde↗
Sound quality and speech reception for prescribed hearing aid frequency responses.
Four different prescriptions of hearing aid insertion gain versus frequency were validated with a group of 26 moderately hearing-impaired, elderly hearing aid users. Three prescriptions were based on calculating the loudness and articulation index (AI) for aided speech, and ranged from a frequency response with moderate high-frequency emphasis, restoring normal loudness for speech peaks, to a response with the greatest high-frequency emphasis, maximizing the AI. The fourth prescription was a well-established formula of the half-gain type. The frequency responses were evaluated by paired comparison ratings of the pleasantness and intelligibility of speech in noise, and by speech identification tests in noise. The subjects rated the flattest response as significantly more pleasant than the other responses, and significantly more intelligible than the prescription with maximal high-frequency emphasis. There were no detectable differences in signal/noise ratios required for 50% speech identification. These results indicate that a prescription that restores normal loudness for speech peaks in each critical band is probably more easily accepted than either a procedure which is intended to make all speech bands equally loud, or a prescription which maximizes the AI.
Aged↗
Plasma homocysteine in venous thromboembolism.
Severe hyperhomocysteinemia due to inborn errors of methionine metabolism results in precocious development of arteriosclerosis and predisposition to venous and arterial thromboembolism. Although the findings of several studies have indicated that mild hyperhomocysteinemia is common in occlusive arterial disease, no similar studies have been made on venous thromboembolism. In this study of subjects under 50 years of age, we found no significant differences in the plasma homocysteine concentrations, either in the fasting state or after methionine loading, between 42 patients with venous thromboembolism and 42 healthy controls. Nonetheless, male patients manifested a tendency toward higher homocysteine concentrations than male controls; 6 patients (14%) versus 2 controls (5%) responded abnormally to methionine loading which might indicate heterozygosity for cystathionine synthase deficiency. Thus, further studies on plasma homocysteine in venous thromboembolism are warranted.
Adult↗
Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus.
The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3 mumols l-1; mean +/- SD, p less than 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6 mumols l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3 mumols l-1; n = 25), and the control subjects (11.0 +/- 3.4 mumols l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels greater than 115 mumols l-1 and/or an albumin:creatinine clearance ratio greater than or equal to 0.02 x 10(-3) (17.0 +/- 5.9 mumols l-1; n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5 mumols l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients.
Adult↗
Altered metabolism of acetaldehyde in blood is not a specific marker of diabetic macroangiopathy.
Previous studies have demonstrated altered acetaldehyde metabolism in diabetics with macroangiopathy. Elimination of acetaldehyde in blood homogenates was studied in 20 non-diabetic survivors of myocardial infarction and 22 healthy controls. The half-life of acetaldehyde was shorter in patients, than in controls (mean values 83 and 150 minutes, respectively, p less than 0.001). Thus, the presence of diabetes is not a prerequisite for altered acetaldehyde metabolism in angiopathy patients. Elimination of acetaldehyde proved to be an enzymatic process, as the elimination was virtually abolished in the presence of chloral hydrate, an inhibitor of aldehyde dehydrogenase. In a previous study, however, results of a more specific assay of aldehyde dehydrogenase showed no correlation to the half-life of acetaldehyde. A possible explanation of the rapid acetaldehyde elimination in angiopathy patients is a low capacity of blood proteins for acetaldehyde binding.
Acetaldehyde↗
The effect of excess daily methionine intake on plasma homocysteine after a methionine loading test in humans.
Impaired homocysteine metabolism might be a risk factor for vascular disease. Peroral methionine loading and post-load determination of methionine and homocysteine in plasma has frequently been used for identifying subjects with genetically impaired homocysteine metabolism. However, a methionine-rich diet induces a more efficient homocysteine catabolism in the rat, which suggests that humans on diets with differing methionine content might respond differently to the methionine loading test. To study this we performed methionine loading in six healthy subjects before and after 2 wk of excessive daily methionine intake (300% of normal). On each occasion plasma homocysteine and methionine were measured at several intervals post-load. However, neither the methionine clearance nor the post-load homocysteine concentrations were affected by excess methionine. We conclude that variations in the daily methionine intake will not influence the methionine loading test.
Adult↗
[Ventilator treatment at home--experiences with old and new methods].
Nocturnal ventilation in respiratory insufficiency due to neuromuscular disease and/or thoracic deformity leads to improvement in the quality of life and daytime arterial blood gases, and also in survival. Several methods for nocturnal ventilation are now available. In this paper we report our experiences of treatment with nocturnal ventilation with various methods in 26 patients in Gothenburg. We conclude that respiratory insufficiency due to neuromuscular disease and/or primary treatment for thoracic deformity should be nocturnal positive pressure ventilation via a nasal mask. If this treatment fails positive pressure ventilation should be administered via special mouth pieces or via tracheostoma.
Aged↗
Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment.
Severe homocysteinemia due to genetic defects either of pyridoxal 5-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) or of enzymes in vitamin B12 and folate metabolism is associated with very early-onset vascular disease. Therefore, we studied homocysteine metabolism in 72 patients presenting before the age of 55 years with occlusive arterial disease of cerebral, carotid, or aorto-iliac vessels. Twenty patients (28%) had basal homocysteinemia; and 26 patients (36%) had abnormal increases of plasma homocysteine after peroral methionine loading, which exceeded the highest value for 46 comparable controls and was within the range for 20 obligate heterozygotes for homocystinuria due to CBS deficiency. Basal plasma homocysteine content was strongly and negatively correlated to vitamin B12 and folate concentrations. Plasma PLP was depressed in most patients but there was no correlation between PLP and homocysteine values. In 20 patients, treatment with pyridoxine hydrochloride (240 mg/day) and folic acid (10 mg/day) reduced fasting homocysteine after 4 weeks by a mean of 53%, and methionine response by a mean of 39%. These data show that a substantial proportion of patients with early-onset vascular disease have impaired homocysteine metabolism, which may contribute to vascular disease, and that the impaired metabolism can be improved easily and without side effects.
Adult↗
Preferred hearing aid gain in everyday use after prescriptive fitting.
The insertion gain preferred by a group of 26 moderately hearing-impaired, elderly hearing-aid users was investigated in everyday listening situations. The subjects used monaural behind-the-ear aids, carefully fitted according to a prescription formula of the half-gain type, validated and used at National Acoustic Laboratories, Australia. The fitting was checked with real-ear measurements of insertion gain and reviewed at one or more follow-up sessions. The subjects were strictly instructed to try the recommended volume control setting before reporting which setting they preferred. The prescription significantly over-estimated preferred gain by about 7 dB. No correlation could be detected between prescribed versus preferred gain differences and the amount of previous hearing-aid use or the degree of subjective hearing problems.
Aged↗
Clinical trials with a programmable hearing aid set for various listening environments.
A conventional hearing aid has a frequency response that does not change much at normal listening levels. It is therefore unlikely that optimal speech intelligibility and optimal listening comfort can be obtained simultaneously, or in different listening environments. With a programmable hearing aid with multiple memories the listener can choose between a range of sound pictures, which increases the chance of finding a suitable frequency curve for each listening situation. The programmable hearing aid with eight separate settings stored in eight memories, was compared with personal hearing aids fitted according to the recommendations of the National Acoustic Laboratories (NAL) by 22 experienced hearing aid users. One memory of the programmable hearing aid was initially fitted according to the NAL recommendation. The other memories were programmed to give variations around that recommendation. One aim was to investigate whether the hearing-impaired user took advantage of different frequency responses to achieve listening improvements in acoustically different environments. Another aim was to evaluate the ergonomic and acoustical features of the programmable hearing aid, compared with other well fitted hearing aids. The evaluations were based on comparisons of the test hearing aid to the personal aid for each subject, looking at speech tests, direct paired comparison judgements, sound quality judgements and interviews. A majority of the subjects experienced substantial benefit from being able to use different frequency response curves in different environments. With the test hearing aid the subjects performed better in speech discrimination tests in noise.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Multi-programmable hearing aid.
A basic problem in hearing-aid fitting is the difficulty in finding one setting optimal to all listening situations that might occur. The objective was to develop a behind-the-ear hearing-aid with a very flexible analog signal processor which is digitally controlled, and a memory with logic, so that the hearing-impaired person can select from eight completely different fittings. To program and adjust this multi-programmable hearing-aid (called MemoryMate) a hearing evaluation and recommendation system (called Master-Fit) has been developed, based on an IBM PS/2 computer. This system offers the dispenser prescriptive fitting methods and performance of real ear measurements. It can be used to manage a client database. Preliminary results from a clinical study conducted in 1988 are presented. The paper also describes the uniqueness of this multi-programmable hearing aid as a powerful new research tool.
Aged↗