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M Sund

Publications and source records attributed to M Sund.

At least 37 records · Page 2Linked to original sources

Association between rheology and components of lipoproteins in human blood. Results from the MONICA project.

BACKGROUND: Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies. METHODS AND RESULTS: We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin. CONCLUSIONS: We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.

Adult↗

Comparison of once daily felodipine 10 mg ER and hydrochlorothiazide 25 mg in the treatment of mild to moderate hypertension.

The efficacy of extended release felodipine 10 mg (ER) o.d., a new dihydropyridine calcium antagonist, and 25 mg hydrochlorothiazide (HCTZ) o.d. have been compared in a randomized, double-blind, crossover trial in 28 mildly to moderately hypertensive subjects (supine diastolic blood pressure, BP, greater than or equal to 95 mm Hg and less than or equal to 110 mm Hg on three separate occasions). Both drugs significantly reduced systolic and diastolic BP in the sitting position felodipine from 157.1/93.8 mm Hg at baseline to 133/78.9 mm Hg 2.5 h after medication and to 138/82.7 mm Hg after 2 weeks of treatment, and HCTZ from 156/95.6 mm Hg to 147/88.4 mm Hg 2.5 h after medication and to 149/89.5 mm Hg also after 2 weeks. A decrease of the same magnitude in standing systolic and diastolic BP was observed after both treatment regimens with the exception of diastolic BP 2.5 h after dosing with HCTZ, which was not significantly lower. At all times (2.5 h and 2 weeks), the reduction in systolic and diastolic BP was greater after felodipine compared to HCTZ. Heart rate was significantly increased after felodipine in both the sitting and standing positions, and both 2.5 h following medication and after 2 weeks of treatment. The difference between the regimens was significant only 2.5 h after dosing. Overall, felodipine 10 mg ER o.d. was superior to 25 mg HCTZ o.d. in lowering BP.

Administration, Oral↗

Association between plasma viscosity and blood pressure. Results from the MONICA-project Augsburg.

The relationship between determinants of blood viscosity and blood pressure (BP) variables was studied in a large sample of a population aged 25 to 64 years. Plasma viscosity, hemoglobin, and total serum protein were examined. Systolic and diastolic BP and the prevalence of hypertension showed a crude positive association with plasma viscosity levels in both sexes. Age, body mass index, and total serum protein appeared to have a confounding effect on this relationship, whereas hemoglobin, smoking behavior, and alcohol consumption did not. A crude positive association was also found between total serum protein levels and the prevalence of hypertension in men and women; however, since total serum protein was treated as a covariable, no further analyses were carried out. In contrast to findings reported in the literature, hemoglobin levels were not correlated with BP variables in either sex. After adjusting for all confounders, a significant main effect of plasma viscosity still was found. However, the magnitude of the effect was not as large as for body mass index, a well-established risk variable for hypertension. These results indicate that BP is positively associated with plasma viscosity. Whether increased plasma viscosity in hypertension constitutes a primary or a secondary phenomenon remains to be answered. Since plasma viscosity is significantly associated with hypertension but any BP variable, increased levels of plasma proteins (particularly fibrinogen as the main determinant of plasma viscosity) may represent the cause for elevated plasma viscosity. This might contribute to persistently increased resistance to blood flow on the microcirculatory level in arterial hypertension.

Adult↗

Catecholamines and the renin-angiotensin-aldosterone system during treatment with felodipine ER or hydrochlorothiazide in essential hypertension.

The neurohumoral responses after 10 mg of felodipine extended release (ER), a new dihydropyridine calcium antagonist, and 25 mg of hydrochlorothiazide (HCTZ) were compared in a randomized, double-blind, crossover trial in 28 mild to moderate hypertensives. Antihypertensive drugs were gradually discontinued. Felodipine ER, 10 mg was given once daily for 2 weeks; after another washout period of 1 week, patients were switched to 25 mg of HCTZ once daily and vice versa. Blood pressure (BP) was measured at baseline, 2.5 h after medication, and after 2 weeks of treatment (24 h postdosing) using an oscillometric device. Felodipine ER and HCTZ both lowered BP effectively. However, felodipine ER was superior in reducing systolic and diastolic BP during the short term and medium term. Treatment with felodipine ER over 2 weeks increased sympathetic outflow as indicated by elevated plasma norepinephrine levels, whereas plasma epinephrine was mainly unaffected, as were plasma renin and aldosterone levels. On the other hand, 25 mg of HCTZ increased plasma renin and aldosterone, but left catecholamines unchanged. Despite persistent increased sympathetic activity, the reduction in BP in this study was more pronounced after felodipine ER as compared to HCTZ. The lack of a difference between heart rates under both medications after 2 weeks of treatment suggests a resetting of the baroreflex by felodipine ER and furthermore that the increased norepinephrine levels may not be clinically relevant, but demonstrate the maintained baroreflex activity. HCTZ, in doses as low as 25 mg, is still capable of stimulating the renin-angiotensin-aldosterone system.

Adult↗

Effects of felodipine ER and hydrochlorothiazide on blood rheology in essential hypertension--a randomized, double-blind, crossover study.

The haemorheological effects of felodipine extended release (ER), a new dihydropyridine calcium antagonist, were compared with hydrochlorothiazide (HCTZ) in 28 mild to moderate hypertensives (18 men and 10 women, aged 30-70 years) in a randomized, double-blind, crossover trial. Antihypertensive drugs were gradually discontinued. Felodipine Er, 10 mg, was given once daily for 2 weeks, and after another wash-out period of 1 week, patients were switched to 25 mg HCTZ, once daily, and vice versa. Whole blood viscosity (BV) at three different shear stresses, haematocrit (Hct), plasma viscosity (PV), red blood cell (RBC) aggregation, RBC deformability, and fibrinogen were measured under standardized conditions 2.5 h after medication, and after 2 week of treatment (24 h post-dosing). Felodipine ER improved BV acutely, but not during treatment over a 2-week period. By contrast, HCTZ did not affect BV, but decreased RBC deformability 2.5 h after medication intake. After 2 weeks of treatment, the negative effect on RBC deformability had increased slightly. Furthermore, fibrinogen and PV were significantly elevated at this stage. In summary, felodipine ER did not improve blood rheology over a 2-week treatment period in this study. HCTZ exhibited marginal but significant negative effects on fibrinogen, PV and indices of RBC deformability, but not on RBC aggregation.

Adult↗

A dose-response analysis of ethylnitrosourea-induced recessive specific-locus mutations in treated spermatogonia of the mouse.

A dose-response analysis was carried out with 2 independent data sets available for ethylnitrosourea-induced specific-locus mutations in spermatogonia of the mouse. It was assumed that the occurrence of mutation is binomially distributed and maximum-likelihood procedures were employed to determine the appropriateness of 4 alternative models, Linear, Linear-Quadratic, Power, and Threshold, in describing the dependence of the binomial parameter on dose. For both data sets, the Threshold model yielded a far superior fit and the threshold dose was estimated to be between 34 and 39 mg/kg. These results are supported by the relatively inefficient response of ethylnitrosourea at lower doses in inducing DNA adducts. Relevant specific-locus mutation results in the mouse for low-dose fractionated treatment as well as the recovery of mutation mosaics indicate the threshold model to be an oversimplification. Rather than a threshold dose below which 100% of the induced DNA adducts are repaired, we propose that some DNA adducts which may eventually be fixed as a mutation persist through a number of repair-competent cell divisions and do not interfere with normal cell function nor do they induce a repair response before being eventually fixed as a mutation. We interpret the thresholded response for ethylnitrosourea-induced specific-locus mutations to be due to a saturable repair process which at lower doses results in ethylnitrosourea being less efficient in inducing mutation. Once this repair process is saturated, a clear dose-related increase in the mutation rate is observed.

Animals↗

Hemodynamic effects of alinidine (ST 567) at rest and during exercise in patients with chronic congestive heart failure.

Selective inhibition of sinus node function offers the possibility to decrease heart rate and reduce myocardial oxygen consumption in patients with impaired cardiac function, if myocardial contractility is not further attenuated. To study the influence of a specific sinus node inhibitor on myocardial function, alinidine was given to 10 patients with chronic congestive heart failure and stable sinus rhythm. Radionuclide ventriculography was used to monitor left ventricular function at rest and during a standardized exercise protocol. After a bolus injection of 45 mg of alinidine followed by infusion of 10 mg/hr, radionuclide studies were repeated 1.5 and 3 hours later. The results show that left ventricular ejection fraction, stroke volume, and end-diastolic volume index were essentially unchanged, whereas cardiac index decreased by 10% at rest and during exercise. Heart rate decreased markedly by 14% at rest and by 13% during exercise. Systolic blood pressure was reduced by 6% at rest and by 14% during exercise. As a result of the marked decrease of these two parameters, a pronounced effect was seen on rate-pressure product with a 19% decrease at rest and a 24% decrease during exercise. No significant side effects were observed. Alinidine might be given to patients with chronic congestive heart failure and sinus rhythm in doses up to 45 mg without exerting a clinically relevant negative inotropic effect. Therefore it may represent an alternative to other drugs when a decrease in heart rate is desired to reduce myocardial oxygen consumption.

Aged↗

Is increased plasma viscosity a risk factor for high blood pressure?

Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two-stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty-four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cholesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and demonstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be answered from cross-sectional data. However, even if plasma hyperviscosity represents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account.

Adult↗

Noninvasive detection of anterior wall asynergies by cardiokymography compared to electrocardiography.

In order to determine the value of cardiokymography in detecting left ventricular (LV) anterior wall asynergies, 80 consecutive patients had a cardiokymogram (CKG) and an electrocardiogram (ECG) on the day prior to coronary angiography. Technically adequate CKGs were obtained in 72 patients (67 men and 5 women, mean age 53 +/- 6.5 years). For validation of regional contraction abnormalities, quantitative LV angiography was used. Stepwise linear discriminant analysis was applied to investigate the diagnostic power of CKG. Sensitivity of the CKG for LV anterior wall asynergy was 67.9% (ECG: 39.6%) and specificity was 68.4% (ECG: 94.7%) on the basis of 1 SD of the mean values of the radial axis shortening of a control group. For 2 SD, the sensitivity was 65.6% (ECG: 56.3%) and the specificity 47.5% (ECG: 90%). By combined testing, the specificity increased to 98.3%, whereas the sensitivity dropped to 26.9%. The improvement of the post-test likelihood for a positive ECG by a positive CKG is especially pronounced in the intermediate prevalence range, whereas for a negative ECG the post-test likelihood can be further decreased by a negative CKG in the intermediate and high prevalence range. The ECG as a single test seems to be the more appropriate noninvasive method for detecting LV anterior wall asynergies; however, the combined use of both ECG and CKG may considerably improve the diagnostic accuracy.

Cineangiography↗

Working classification of chronic myeloproliferative disorders based on histological, haematological, and clinical findings.

Bone marrow biopsies of 850 patients with chronic myeloproliferative disorders were taken at initial diagnosis; and 169 sequential biopsies over periods of one to 188 months. Three micron sections of all biopsies were evaluated semiquantitatively with reference to the proliferating cell lines, anomalies of megakaryocytes, and fibrosis or osteosclerosis. Correlations between initial histological findings, clinical, haematological, and survival data were analysed statistically. The predominant cell lines distinguished the classical entities of polycythaemia vera, primary thrombocythaemia, and chronic myeloid leukaemia and correlated with their different prognoses, while megakaryocytes characterised subgroups that were prone to fibrotic or blastic transformation. Based on the initial histological, clinical, and haematological data analysed a working classification of chronic myeloproliferative disorders was proposed that permits recognition of both typical and atypical cases of chronic myeloproliferative disorders.

Adolescent↗

Mutational changes of quantitative morphological traits in the convict cichlid (Cichlasoma nigrofasciatum Guenther) after irradiation of parental spermatogonia and oogonia with different doses of X-rays.

10 continuous and 6 discrete variables of body dimensions as well as 16 proportions calculated from them were determined in postirradiation F1 convict cichlid fish (Cichlasoma nigrofasciatum) which were derived from spermatogonia and oogonia both exposed to either 0 (controls), 250, 500, 750, 1000, or 2000 R of X-rays. While no interactions with sex or radiation dose were found, clear dosage effects and some sex effects occurred. The highest response for almost all quantitative traits examined as well as for variants of coloration or of vertebral aberrations appeared after 250 R to both parental germ cells. The lowest effectiveness was observed for almost all characters under investigation after 0 and 500 R. Accordingly, the largest difference between the 6 different treatment groups was found between 250 and 500 R, followed by 250 and 0, 250 and 1000, and 250 and 750 R to parental gonia. The present finding on the alterations of quantitative morphological traits completely corresponds to the changes of intraspecific aggressiveness as found for the same individual fish in a previous study thus confirming the complete congruence of the mutational response of quantitative morphological characters with that of behavioral traits to ionizing radiation.

Animals↗

[Quality assurance and quality control of blood pressure measurements. Experiences with the Munich blood pressure study].

More than 12 000 blood pressure measurements were taken in the Munich Blood Pressure Study (MBS). The reliability of these blood pressure measurements is reported. After consideration of possibilities for systematic and random measurement errors we present methods used in the MBS to control and assess the quality of the blood pressure readings over a long period of time: measures for standardizing the recording conditions and procedures; training and testing of the field staff using audio tape-recording and simultaneous measurements with a double stethoscope; analysis of inter- and intraobserver-variation relative to that of reference measurements; analysis of observer preferences for certain terminal digits. With the application of these methods one can indeed successfully reduce observer variability to a tolerable amount even over a considerable period of time.

Blood Pressure Determination↗

Chronic myeloproliferative disorders (CMPD).

The wide clinical range of CMPD can be understood as leukaemia of pluripotent stem cells according to the pathogenic concepts reviewed above. Blastic metamorphoses of CMPD are regressions to a more primitive level of cellular differentiation. The predominant proliferative cell line characterizes the classical entities of PV, PT and CML, and their different prognoses. Pure erythrocytic and megakaryocytic proliferations are more compatible with sustained physiologic bone marrow functions than granulocytic proliferations. The combinations of granulocytic and megakaryocytic growth are especially prone to develop MF/OMS, in which participation of immune reactions, of granulocytic and of platelet factors is probable. An etiologic role for ineffective thrombocytopoiesis is supported by experimental as well as by histologic evidence. Myelofibrosis and osteomyelosclerosis may have similar causes, but develop independently. The prevalence of the female sex among thrombocythaemic patients was proven statistically also for the increase of giant type megakaryocytes in the form of clusters in the bone marrow, and for longer median survival of females in CMPD, especially when there is megakaryocytosis in the bone marrow. It is assumed that females may be better protected against the detrimentous effects of abnormal platelet production. An arbitrary classification according to haematologic and histologic criteria was applied to PV, PT and CML, and groups with typical and atypical haematologic and histologic signs were distinguished. The latter cannot be separated from each other by their various haematologic manifestations, but by histology and their different propensity to progress into more immature and/or fibrotic stages. Three major groups are characterized by histology: mixed granulocytic-megakaryocytic myelosis with giant megakaryocytic clusters, a similar variant with diffuse distribution of giant megakaryocytes, and immature and/or pleomorphic megakaryocytic myelosis. Transitions from each of these groups have been observed as well as transitions from each of the typical CMPD-entities into these less typical forms. CML, frequently accompanied by dwarf-megakaryocytes, often develops into pleomorphic megakaryocytic or blastic myelosis. Blastic dedifferentiation and myelofibrosis manifest themselves as closely related end stages, to which principally all groups proceed after a longer or shorter period of time, modified by the proliferating cell lines in each group. Clinical, experimental and histologic evidence of this natural history has been reviewed, with special emphasis on the re-evaluation of technically optimal bone marrow biopsies of untreated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Bone marrow histology in hairy cell leukemia. Identification of subtypes and their prognostic significance.

Bone marrow biopsy specimens taken on initial investigation of 134 patients with hairy cell leukemia (HCL) were processed into plastic, and sections cut at 3 microns were used for histologic and histomorphometric evaluation. Twenty-four clinical, 10 histologic, and four histomorphometric variables were tested for their prognostic significance. Bone marrow involvement was found in all cases, and on the basis of their morphology, the hairy cells were divided into three types: ovoid (47%), convoluted (37%), and indented (16%); this classification proved to be highly significant in the test statistics, with median survivals for the three groups of 56, 12, and 5 months, respectively. The characteristic nuclear features of the three types also were identified in smears of peripheral blood, in sections of spleen, and by electron microscopy. In addition, significant differences were found when the patients were grouped according to the tumor cell mass (volume %) in the biopsy sections, with median survivals of 55, 21, and 8 months noted for less than 20 vol%, 20-50 vol%, and greater than 50 vol%, respectively. Other factors with prognostic relevance were cytoplasmic inclusion bodies in the hairy cells (HC) and a number of clinical variables, including initial values of Hb and ESR, and platelets and monocytes in the peripheral blood. These results confirm that the bone marrow always is involved in HCL and its histology is diagnostic; that HCL may be classified according to the predominant neoplastic cell type; and that the patients may be staged on the basis of the tumor cell burden in the bone marrow biopsy.

Adult↗

Bone marrow histology in myeloma: its importance in diagnosis, prognosis, classification and staging.

A study has been made of 420 bone marrow biopsies from patients with multiple myeloma (220), idiopathic monoclonal gammapathy (50), reactive plasmacytosis (42) and solitary plasmacytoma (22). Histology and immunohistological parameters were more reliable than cytology in distinguishing a reactive from a neoplastic plasmacytosis. Histological variables were correlated with the clinical features of the patients to determine the factors which were of value in predicting prognosis. Plasma cell maturity and the extent of infiltration in the biopsy by myeloma cells proved to be highly significant in predicting the duration of survival. On the basis of these criteria multiple myeloma was classified into two types: plasmacytic of low-grade malignancy and plasmablastic of high-grade malignancy; and into three stages which accurately reflected the progression of the disease. We conclude that a bone biopsy provides useful information for the diagnosis, classification and staging of patients with multiple myeloma.

Bone Marrow↗