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Biomedical subjects

W Burger

Publications and source records attributed to W Burger.

At least 73 records · Page 4Linked to original sources

Right ventricular volumes determined by computerized thermodilution in ischaemic heart disease: effect of exercise and nitroglycerin.

In 29 patients with stable ischaemic heart disease, right heart catheterization was performed to assess the effect of exercise and nitroglycerin on right ventricular volumes, which were determined by a new computerized thermodilution system. The coefficient of variation for the determination of right ventricular ejection fraction averaged 11.0 +/- 6.2% (mean +/- standard deviation) at rest and 14.6 +/- 8.1% during exercise. End-diastolic volume index increased from 90 (65-127) ml/m2 [median (range)] at rest to 101 (81-130) ml/m2 (P less than or equal to 0.0001) during exercise. Nitroglycerin reduced this parameter at rest to 77 (44-121) ml/m2 (P less than or equal to 0.05), without affecting exercise values. Resting right ventricular ejection fraction (55 [44-64]%) was diminished by both exercise (to 52 [39-62]%, P less than or equal to 0.05) and nitroglycerin (to 53 [40-65]%, P less than or equal to 0.05). Additionally, nitroglycerin reduced the exercise induced decrease of right ventricular ejection fraction from -3 (-20-10)% to -1 (-15-14)% (P less than or equal to 0.01). Nitroglycerin diminished the left-to-right interventricular end-diastolic pressure gradient, which was estimated from the difference between pulmonary capillary wedge pressure and right atrial pressure, at rest from 6 (1-17) mmHg to 5 (2-14) mmHg (P less than or equal to 0.05) and during exercise from 17 (6-31) mmHg to 14 (1-33) mmHg (P less than or equal to 0.001). It is concluded, that both exercise and nitroglycerin cause significant changes in right ventricular volumes.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

[Therapy of diabetes mellitus in childhood and adolescence. Goals, evaluation criteria and results].

We report on the results of longterm treatment of 466 children and adolescents with Type I diabetes (IDDM) between 1980 to 1989. Of these, in, 1989, 240 patients, aged 1 to 20 years, were under continuous treatment, 168 (70%) with CT and 72 (30%) with ICT. For 112 of 466 patients (24%) the medians of all measured HBA1c values were calculated to be less than or equal to 7.7%, for 53% between 7.8 and 9.6%, and for 24% greater than or equal to 9.7%. The respective percentages for the ICT patients were found to be 32, 48, and 20%. Medical treatment was accompanied by the continuous offer of education and psychosocial support. In order to reduce the risks for secondary vascular complications, good glycemic control is important in particular during postpubertal years. Therefore children and adolescents need support to obtain both, the acceptance of their disease and the individual responsibility necessary to endure any intensified treatment regimen. Furthermore, the effects of any therapeutic approach should not be measured by glycated haemoglobin only, but in particular by the young subject's individual development and his gain in courage to go on.

Adolescent↗

Antiischemic and hemodynamic effects of intravenous isradipine, a new calcium antagonist, in coronary heart disease: a comparative double-blind cross-over study with nifedipine.

In a double-blind cross-over study, 10 patients with stable angina pectoris owing to coronary heart disease were investigated in supine position during rest and bicycle exercise for the effect of 0.4 mg of intravenous (i.v.) isradipine in comparison to 2 mg i.v. nifedipine on cardiac hemodynamics and myocardial ischemia. At rest, both drugs significantly decreased total peripheral resistance (TPR) and mean arterial blood pressure (MAP), whereas heart rate (HR) increased. The pressures and resistance of the pulmonary circulation remained uninfluenced at rest. During symptom limited-exercise, both medications reduced TPR despite an unchanged MAP. Mean pulmonary artery pressure decreased significantly after both medications, whereas right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) decreased significantly only after nifedipine. The improvement of mean ischemic ST-segment depression averaged 44 +/- 6% (mean +/- SEM, p less than or equal to 0.01) after nifedipine and 45 +/- 7% (p less than or equal to 0.01) after isradipine. The time until angina appeared increased after isradipine by 89 +/- 28% (p less than or equal to 0.05) and after nifedipine by 105 +/- 42% (p less than or equal to 0.01). Significant differences between the two medications appeared only for cardiac output (CO) at rest (p less than or equal to 0.05), during which state the increase after isradipine was higher than after nifedipine, and for exercise HR (p less than or equal to 0.01), during which state only nifedipine induced a significant increase in frequency. We conclude that at the chosen dosages the hemodynamic and antiischemic effects of isradipine are similar to the effects that occur after nifedipine.

Calcium Channel Blockers↗

Hemodynamic and antianginal effects during rest and exercise of intravenous isradipine, a new dihydropyridine calcium antagonist.

In an open randomized study, hemodynamic and antianginal effects of nifedipine and the new dihydropyridine derivative isradipine were compared in patients with stable, angiographically confirmed coronary heart disease. Right heart hemodynamics, systemic arterial blood pressure, ECG, and drug plasma concentrations were measured before medication at rest and exercise, after infusions of increasing doses at rest, and again after treatment at rest and exercise. A linear relationship between serum concentrations and cumulated dosages was obtained for both drugs. At rest, both drugs significantly increased cardiac output and heart rate. The reduction of arterial blood pressure was significantly greater after isradipine (systolic from 148 +/- 3 to 104 +/- 3 mmHg; diastolic from 90 +/- 4 to 58 +/- 2 mmHg) than after nifedipine (systolic 149 +/- 6 to 125 +/- 4 mmHg; diastolic 92 +/- 4 to 76 +/- 3 mmHg). The minimal effective plasma level of isradipine regarding blood pressure reduction was estimated at 5 ng/ml (nifedipine: 10-25 ng/ml). During exercise both medications significantly reduced mean pulmonary artery pressure (isradipine: 40 +/- 3 to 20 +/- 1 mmHg, nifedipine: 37 +/- 4 to 22 +/- 1 mmHg), pulmonary artery wedge pressure (isradipine: 23 +/- 3 to 10 +/- 1 mmHg, nifedipine 24 +/- 3 to 14 +/- 1 mmHg), and diastolic arterial pressure (isradipine: 103 +/- 3 to 73 +/- 4 mmHg, nifedipine: 99 +/- 3 to 91 +/- 2 mmHg), whereas systolic pressure was reduced by only isradipine (189 +/- 4 to 147 +/- 5 mmHg). Neither medication significantly changed electrocardiographic ST depression during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Long-term therapy following myocardial infarct with isosorbide dinitrate in a low and high dose].

The favorable response to nitrates in the case of coronary heart diseases is based on both reduction in left ventricular pre- and afterload and improvement in coronary flow. These effects were studied in the setting of a long-term ISDN therapy with reference to the prognosis of patients after myocardial infarction. Following acute treatment in the respective hospitals, 608 patients with myocardial infarctions were allocated to two double-blind treatment groups with different ISDN dosage levels (group 1 = 5 x 2.5 mg i.d.; group 2 = 5 x 40 mg i.d.) and followed up over a period of 2 years. No differences were found with regard to the end points sudden cardiac death, reinfraction, and indication for revascularization. There was, however, a more frequent additional administration of calciumantagonists to patients of the low-dose group (p less than 0.05), a more frequent drop-out due to the lack of beneficial therapeutic results, and a more exceptional drop-out due to side effects in patients treated with low doses of ISDN (n.s.). The absence of any significant difference with regard to the end points might be attributed to; 1) a loss of potency of high-dose ISDN and simultaneous ineffectiveness of low-dose ISDN; 2) an efficacy of low doses; 3) an absence of actual influence on the target parameters, and 4) an inadequate follow-up time period.

Coronary Circulation↗

Prevalence of coeliac disease in diabetic children and adolescents. A multicentre study.

Screening for coeliac disease (CD) with serum antigliadin antibodies (AGA) was performed in 1032 diabetic children and adolescents. In 8 children CD had been diagnosed before study entry. Of the remaining 1024 children, 33 had an elevated AGA titre in the first serum sample. On follow-up an elevated AGA titre was confirmed in only 17 of 31 patients. Nine of the repeatedly positive patients underwent jejunal biopsy, and CD was diagnosed in two asymptomatic patients; both were positive for IgG- and IgA-AGA. Among 10 AGA-positive patients in whom biopsies could not be performed, only 1 showed IgA-AGA and thus carried a high risk for CD. From our results we estimate a prevalence of CD in Swiss and German diabetic children between 1.1% and 1.3%. False-positive AGA titres occurred significantly more often in patients with diabetes duration of less than 1 year. AGA testing reached a specificity of 99% if performed at least 1 year after the onset of diabetes. Children suffering from both diabetes and CD showed a diabetes manifestation at a significantly younger age than non-coeliac patients, whereas CD tended to be diagnosed at a remarkably late age.

Adolescent↗

The internal dynamics of gene 32 protein-DNA complexes studied by quasi-elastic light scattering.

The hydrodynamic properties of large homodisperse single stranded DNAs complexed with the helix destabilizing protein of phage T4, the product of gene 32 (GP32), have been measured. The results suggest a size of the binding site between 8 and 10 nucleotides/GP32 molecule, in reasonable agreement with earlier work on a complex between GP32 and single stranded 145 base DNA. From static light scattering experiments it is concluded that the persistence length of these complexes is about 30 nm, distinctly smaller than the generally accepted value for double stranded DNA. The quasi-elastic light scattering properties of the DNA-GP32 complexes were determined. The variation of the apparent translation diffusion coefficient Dapp with the scattering vector q was analyzed using the discrete ISMF and Rouse-Zimm models [S.C. Lin et al., Biopolymers 17 (1978) 425]. The model parameters that followed from the fit of Dapp versus q2 and from an extensive global analysis of the actually measured autocorrelation functions agreed with the notion that these DNA-protein complexes are indeed rather flexible. The continuous Soda model [K. Soda, Macromolecules 17 (1984) 2365] could successfully explain the variation of Dapp versus q2, assuming a persistence length of 30 nm and a base-base distance in the complex of 0.44 nm.

Bacteriophage lambda↗

Effects of 5 mg sublingual nitrendipine in patients with precapillary pulmonary hypertension due to pulmonary fibrosis.

In 10 patients with precapillary pulmonary hypertension due to pulmonary fibrosis, the arterial blood pressure, right heart hemodynamics, cardiac output, and arterial oxygen partial pressure were measured to evaluate the benefits of acute sublingual (5 mg) nitrendipine. Additionally, the effect of oxygen enriched air was compared to control. At rest, nitrendipine significantly diminished arterial blood pressure [102 +/- 3 to 93 +/- 3 mm Hg (mean +/- SEM)], right atrial pressure (5.7 +/- 0.9 to 3.4 +/- 0.8 mm Hg), mean pulmonary artery pressure (33.4 +/- 3.5 to 29.8 +/- 3.3 mm Hg), and pulmonary artery wedge pressure (13.0 +/- 2.0 to 6.8 +/- 0.8 mm Hg). During exercise, nitrendipine reduced mean pulmonary artery pressure (54.5 +/- 4.8 to 49.3 +/- 4.7 mm Hg) and right atrial pressure (9.3 +/- 1.3 to 6.8 +/- 1.4 mm Hg). A diminuation of arterial partial oxygen pressure did not occur at rest (63.2 +/- 3.8 mm Hg) or during exercise (50.9 +/- 5.1 mm Hg). Thus, nitrendipine causes a slight but significant improvement of right heart hemodynamics. The occurrence of arteriovenous intrapulmonary shunting due to vasodilatating effects of nitrendipine can be excluded. Also, nitrendipine can safely be used in combined arterial hypertension and pulmonary fibrosis.

Administration, Sublingual↗

Long-term monitoring of treatment with recombinant human growth hormone by serial determinations of type III procollagen-related antigens in serum.

Inasmuch as recombinant human growth hormone is now more generally available for the treatment of different types of short stature, there is a need for better short-term indicators of treatment success. In healthy children, serum concentrations of antigens related to the aminoterminal propeptide of type III procollagen (P-III-NP) closely follow the growth velocity curve. P-III-NP was measured longitudinally in 20 children with growth hormone deficiency during 6 months of human growth hormone substitution therapy. Two different radioimmunoassay systems were used; one recognizes predominantly the intact propeptide showing a lesser affinity to a smaller monomeric peptide (RIAgnost assay), while the other assay detects both forms equally (FAB assay). These results were compared to the growth response [median 5.6 (0.4 to 13.9) cm in 6 months] and to other established growth correlated parameters (somatomedin C, alkaline phosphatase). A relatively better growth response correlated significantly with high pretreatment P-III-NP (RIAgnost assay) values (r = 0.56) and delayed bone age (r = -0.70). A combination of these parameters in multiple regression analysis increased the cumulative prediction value to above 60% (r2 = 0.61). On the other hand, P-III-NP (FAB assay) values proved to be best in monitoring treatment, correlating with the individual growth rate during the first 3 months (r = 0.40; p less than 0.05), during the consecutive 3 months (r = 0.66; p less than 0.001), and during the total 6-month period (r = 0.46; p less than 0.05). All other parameters showed associations to growth only during some treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Interaction of (2,3)-methylenepenams with penicillin-binding proteins.

A series of (2,3)-methylenepenams were examined with respect to binding to essential penicillin-binding proteins (PBPs) in Escherichia coli and Staphylococcus aureus. The compounds were also examined with respect to their interaction with Streptomyces strain R61 DD-carboxypeptidase. The alpha isomer of (2,3)-methylene penicillin G bound to PBP 3 of E. coli and other enterobacteria at 0.1 to 10 micrograms/ml. The beta isomer bound to PBP 3 at 100 micrograms/ml. Either isomer bound to PBPs 1b and 2 of E. coli only at 100 micrograms/ml. The alpha, but not the beta, isomer also bound to PBP 2 of S. aureus at 0.1 micrograms/ml. Binding studies with radiolabeled compounds indicated the binding to be covalent and revealed no additional binding proteins. (2,3)-Methylenepenams active against E. coli bound to PBP 3 and induced filamentation. The compounds also inhibited Streptomyces strain R61 DD-carboxypeptidase with apparent 50% inhibitory concentrations as low as 10(-7) M. The two (2,3)-methylene penicillin G isomers bound to the enzyme covalently, most likely at the same site as penicillin G since partial proteolysis after binding radiolabeled compounds produced similar peptide patterns. The bound beta isomer was released with a half-time similar to that of penicillin G (70 min at 30 degrees C), while the alpha isomer was released with a longer half-time (13 h at 30 degrees C). With either isomer, the major release product was phenylacetylglycine, suggesting C-5-C-6 cleavage.

Bacterial Proteins↗

Compartmentation and functional mechanisms in myocardial failure and myocardial infarction.

Changes in compartmentation and specific mechanism in acute myocardial failure due to global ischemia and in regional myocardial ischemia in dog hearts are described. Ischemic failure was produced by periodic arrest of flow to supported heart preparations perfused with a fluorocarbon (FC-43). Sarcolemmal vesicles (SL) prepared from ischemic failing heart preparations exhibited diminished Ca++ binding and phosphorylation. TA-064, a beta-1-agonist partially abolished the reduction in Ca++ binding and phosphorylation of SL vesicles. The addition of cyclic-AMP (cAMP) and of protein kinase (PK) increased phosphorylation of SL vesicles obtained from non failing heart preparations. Combination of cAMP and of PK had the greatest effect. In contrast to myocardial failure, myocardial infarction is known to produce a large variety of specific disturbances in intermediary cardiac metabolism. Apparently in ischemic failing heart preparations, Ca++ binding and phosphorylation by SL are deficient. The results with TA-064 and isoproterenol suggest that phosphorylation of SL may play a role in the positive inotropic effect of beta-1-agonists.

Adenosine Triphosphate↗

Prevalence and development of retinopathy in children and adolescents with type 1 (insulin-dependent) diabetes mellitus. A longitudinal study.

In 231 subjects with Type 1 diabetes mellitus aged 17.6 +/- 4.0 years, with a diabetes duration of 8.5 +/- 4.9 years at the end of the study, the prevalence and the development of retinopathy during a period of 5 years were studied. All patients were examined between one and six times both by ophthalmoscopy and fluorescein angiography. A total of 626 fluorescein angiographies were evaluated. By the end of the study, 109 out of 231 patients (47%) had developed retinal changes, half of which were classified as minimal (less than 5 microaneurysms). Thirty-eight patients (35% of those affected) had background (n = 28) or proliferative (n = 10) retinopathy. In subjects less than 15 years of age and diabetic for less than 5 years, retinal lesions were rare. With increasing age and duration of diabetes, both the prevalence and severity of retinal changes increased markedly. Life-table analysis was used to calculate the median individual risk for the development of early retinal changes, which was 9.1 years of diabetes duration. This risk differed in sub-groups with different ages at onset of diabetes, i.e. 12.1, 8.9 and 6.6 years (p less than 0.0001), with diabetes starting below 4, between 5 and 9, and after 10 years of age respectively. After 18 years of diabetes, every patient demonstrated at least incipient structural changes. Fluorescein angiography allowed the detection of retinopathy, on average, four years earlier than with ophthalmoscopy. The median interval between the 'onset' of retinopathy, as indicated by a few microaneurysms, and background retinopathy was 5 years.

Actuarial Analysis↗

Risk factors for the development of retinopathy in children and adolescents with type 1 (insulin-dependent) diabetes mellitus.

In our preceding paper, the prevalence and development of retinopathy in 231 Type 1 diabetic children and adolescents were reported to be associated with the duration of diabetes and its age at onset. This paper analyses the relationships between the development of retinopathy and the following factors: age, sex, puberty, blood pressure, insulin dosage, HLA antigens, long-term glycaemic control, and serum cholesterol and triglycerides. All these variables were longitudinally evaluated in a cohort of 322 insulin-dependent patients aged 16.2 +/- 4.9 years with diabetes for 7.4 +/- 5.2 years, including those 231 subjects whose eyes were examined once or repeatedly by ophthalmoscopy and fluorescein angiography. Long-term glycaemic control from the onset of diabetes to the retinal examination was assessed by both an arbitrary score comprising different parameters and by mean values of glycosylated haemoglobin, and was categorised as good, fair, and poor. With life-table analysis, the overall median individual risk for developing early retinal changes (9.1 years) was found to be significantly influenced by glycaemic control. Minimal lesions developed earlier (8.0 years) with poor control, but later with fair (10.5 years) and good glycaemic control (12.5 years) (p less than 0.01). Mean HbA1 values below 10% delayed the onset of both incipient (10.8 years) and background retinopathy (16.6 years), while values above 10% advanced it (8.0 and 11.8 years respectively) (p less than 0.05 and less than 0.008). By multivariate regression and stepwise discrimination analyses, only 4 out of 14 variables were found to exert significant independent influences on the development of retinopathy: diabetes duration, long-term glycaemic control, serum triglycerides and age.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Annual progression of retinopathy in conventionally treated children and adolescents with type I diabetes mellitus.

In a cohort of 268 type I diabetic patients, aged 19.6 +/- 4.1 years (Mean +/- 1 SD), with a diabetes duration of 10.4 +/- 4.9 years, treated by the same team, using the same conventional treatment regime during the total observation period, the progression rate of early retinopathy within the first two decades of diabetes was deduced from observed transitions of the retinal status from one stage of retinopathy (as defined by fluorescein angiography) to a higher one (Malone et al., 1977) within one year. A total number of 83 such events were evaluated. After a gradual development of earliest changes within the fifth year of diabetes, the median annual rate of progression was found to be 12-13%, independent of the previous duration of diabetes and the actual retinal state.

Adolescent↗

Effect of intact endothelium against platelet-induced coronary artery spasm in isolated rabbit hearts.

Effects of collagen-activated washed rabbit platelets on coronary arteries with and without intact endothelium were studied in a supported rabbit heart preparation using a perfluorocarbon (FC-43) as perfusate. The vascular diameter of obtuse marginal coronary arteries was determined by means of gated color arteriography (injection of patent blue dye). Endothelial denudation of the obtuse marginal artery was accomplished by scraping the lumen with a roughened plastic tubing. Injection of washed platelets (10 ml with about 500,000 platelets/microliters) not treated with collagen failed to constrict coronary arteries either with intact or denuded endothelium. In contrast, injection of platelet suspension immediately after activation with collagen caused vasoconstriction of denuded obtuse marginal coronary arteries in 10 of 14 cases. In 6 preparations occlusion was complete, lasting up to 16 minutes. In arteries with intact endothelium, no coronary vasoconstriction occurred. In hearts with coronary artery spasm, total coronary vascular resistance increased significantly. This study furnishes additional evidence that endothelial lesions are a contributory factor for large coronary artery spasm and that endothelial cells possess a protective function against vasoconstrictor substances released from aggregating platelets.

Animals↗

A model for the study of coronary spasm induced changes in cardiac metabolism.

A model is described which permits the study of localized and generalized arterial spasm in the intact working perfused rabbit heart with a perfluorochemical (FC-43) as perfusate. Coronary arteries were visualized by intraatrial injection of Patent Blue Dye with gated photography. Localized spasm resulted from topical spray of histamine (40 mumols) on the epicardial surface overlying an obtuse marginal artery. Before and following topical administration of histamine, regional coronary flow was determined using radioisotope-labeled microspheres. Generalized arterial spasm was initiated by intraatrial injection of histamine (10 mumols). After topical administration, abtuse marginal artery diameter decreased by 57%; large vessel resistance rose 32 fold; 20% rise of total coronary resistance resulted in a slight reduction of total coronary flow (16%). Heart rate, cardiac output, dP/dtmax and myocardial oxygen consumption did not change. However, regional coronary flow in the myocardium supplied by the affected artery diminished 21% resulting in ischemic changes in redox pairs. After intraatrial injection of histamine, changes were more pronounced. Obtuse marginal artery diameter declined by 88% resulting in 3300-fold rise of large vessel resistance. Total coronary resistance increased 150%, coronary flow and cardiac output diminished (56% and 24%). Both heart rate and dP/dtmax increased (16% and 17%). Generalized coronary spasm after intraatrial histamine injection resulted in severe metabolic effects: Myocardial oxygen consumption (-48%); ATP (-29%); creatine phosphate (-34%); redox ratios, alpha-glycerophosphate/dihydroxyacetone phosphate and lactate/pyruvate, increased by 449% and 114%, respectively. The findings illustrate that localized and generalized coronary spasm can be produced and quantitated in a working heart model.

Animals↗