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Biomedical subjects

W Kramer

Publications and source records attributed to W Kramer.

At least 181 records · Page 10Linked to original sources
PubMed1983

Myocardial perfusion and left ventricular performance during long and short haemodialysis in patients with coronary heart disease.

In seven patients with confirmed coronary heart disease and stable blood pressure control acetate haemodialysis improved left ventricular performance and exercise tolerance. Similar positive effects were obtained by a four hour dialysis (one litre fluid removal/hour) and a two hour dialysis (two litre fluid removal/hour). In this group of patients weight gain and overhydration between dialyses appears to be the major risk for myocardial perfusion and rapid weight reduction by acetate dialysis appears adequate therapy. One practical consequence from our study is to minimise fluid overload in coronary heart disease and we try to avoid iatrogenic induction of thirst by decreasing dialysate sodium from 140 mmol/litre to 125-135 mmol/litre. As far as myocardial risk factors are concerned it appears that it is more important to focus on interdialysis weight gains than on acute dialysis therapy.

Adult↗
PubMed1983

Ultrashort hemodiafiltration: efficiency and hemodynamic tolerance.

During hemodiafiltration, solutes are removed simultaneously by diffusion and convection. Increase of the fraction removed by diffusion, by using large surface area hemodiafilters, allows a further reduction of treatment time by hemodiafiltration. To assess the efficiency and biochemical safety of ultrashort treatment (mean duration 3 X 105 +/- 14 min/week) six patients (age 22-64) have been observed for six months. There were no differences in the clinical state or in the biochemical parameters compared to those found during the preceding hemodialysis period (3 X 240 min/week). In a second study, hemodynamic measurements in six individual patients aged 34-72 have been compared during a 90 min ultrashort hemodiafiltration (90 min) and during a 240 min hemodialysis. Circulatory stability was maintained during hemodiafiltration despite a rate of fluid removal that was 2.5 times that which occurred during hemodialysis. During both techniques there was a reduction of stroke volume and an adequate norepinephrine-induced rise of peripheral resistance. Plasma levels of vasopressin did not change during treatment. There were no differences in the frequency and quality of premature ventricular beats between the two treatments. The data from the two studies suggests that ultrashort hemodiafiltration (3 X 1.5-2 hr/week) provides biochemical safety as well as hemodynamic stability.

Adult↗
PubMed1982

Directed mutagenesis of DNA cloned in filamentous phage: influence of hemimethylated GATC sites on marker recovery from restriction fragments.

Gapped duplex DNA molecules of recombinant genomes of filamentous phage are constructed in vitro. Denatured restriction fragments covering (part of) the precisely constructed gap are hybridized to the gapped duplex DNA molecules to form ternary duplices. The two strands of the ternary duplex molecules carry different genetic markers within the region spanned by the restriction fragment leading to a one base pair mismatch or to an insertion loop of 93 nucleotides, respectively. The two strands also vary with respect to A-methylation in GATC sites. In cases of asymmetrical methylation, transfection of E. coli with these heteroduplex molecules leads to marker recoveries with a pronounced bias in favour of the marker encoded by the methylated strand. This effect at least partly explains the comparably low marker yields achieved in previous directed mutagenesis experiments using filamentous phage as the vector. The results suggest how these procedures can be optimized. Precise construction of a 93 bp insertion of 9.5% marker yield is described.

Base Composition↗
PubMed1982

Clinical pharmacology of bruceantin by radioimmunoassay.

During the phase I clinical trial of a new antitumor agent, bruceantin, the pharmacology was studied in 18 cancer patients. The drug was infused intravenously (IV) for 3 h at doses ranging from 1 to 3.6 mg/m2 per day for 5 days. The plasma drug disappearance curves were biphasic, with a fast initial half-life of less than 15 min. The second half-life (t1/2 beta) varied from 0.7 to 38 h among different patients and was not dose-related. The difference between the t1/2 beta on day 1 and that on day 5 was not significant. In patients with normal liver function, the mean plasma concentration at the end of infusion was 22 ng/ml, and the value of the area under the concentration X time curve (AUC) was 111 (ng/ml)h. In contrast, in patients with abnormal liver function the corresponding values were 115 ng/ml and 830 (ng/ml)h, respectively. In addition, these patients had a slower elimination half-life of 10.9 h and a decreased total clearance of 157 ml/min/m2, as compared with 2.6 h and 671 ml/min/m2, respectively, for the normal group. All these differences were statistically significant. Patients with abnormal liver function developed more severe toxicity, including fever, severe nausea, vomiting, and hypotension. Two patients with severe hepatic dysfunction received a reduced dose and developed no toxicity. These results demonstrated the importance of the effects of liver dysfunction on drug disposition and showed that the dosage should be reduced in patients with hepatic dysfunction.

Antineoplastic Agents, Phytogenic↗
PubMed1982

Hemodynamic and myocardial energetic changes induced by the new cardiotonic agent, AR-L 115, in patients with coronary artery disease.

AR-L 115 has been shown to improve left ventricular (LV) pump function in patients with advanced congestive cardiomyopathy by the intravenous and oral routes. Since AR-L 115 effects on myocardial oxygen consumption (MVO2) and coronary blood flow (CSF) are unknown, the hemodynamic, myocardial metabolic, and ECG responses to AR-L 115 (2 mg/kg bolus) were monitored at 9-, 14-, and 9-minute intervals in seven patients with coronary disease, exhibiting ischemia during pacing stress only. Maximal responses occurred at the fourteenth minute after AR-L 115. There were (average) increases in cardiac index by 30%, heart rate by 19%, CSF by 39%, MVO2 by 34%, and LV dp/dt max by 27%. There were (average) decreases in peak LV systolic pressure by 13%, LV end-diastolic pressure by 42%, systemic vascular resistance by 34%, and in coronary vascular resistance by 37%. All changes were significant (p less than 0.05). Myocardial lactate extraction, stroke work index, and stroke index remained unchanged (p greater than 0.05). The modest increase in MVO2 is possibly explained by the increase in contractility being partially offset by reductions in LV preload and afterload. AR-L 115-improved LV pump function was accompanied by moderate increases in MVO2 and CSF but without evidence of myocardial ischemia.

Cardiotonic Agents↗
PubMed1982

Bile-salt-binding polypeptides in plasma membranes of hepatocytes revealed by photoaffinity labelling.

1. Photoaffinity labelling of a subfraction of plasma membranes of rat liver, enriched with sinusoidal surfaces, with the sodium salts of (3 beta-azido-7 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid, (7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid and (11 xi-azido-12-oxo-3 alpha,7 alpha-dihydroxy- 5 beta-cholan-24-oyl)-2-amino[2-3H(N)]ethanesulfonic acid resulted with each derivative in a clear covalent incorporation of radioactivity into polypeptides with the apparent molecular weights of 67,000, 52,000, 48,000, 43,000 and about 20,000. 2. Photoaffinity labelling of a membrane subfraction predominantly composed of bile canalicular membranes by the photolabile derivatives of the conjugated bile salts also showed covalent incorporation of radioactivity into polypeptides of the same apparent molecular weights as with the subfraction enriched with the sinusoidal membranes. 3. The extent of photoaffinity labelling of the different membrane polypeptides is dependent upon the photolabile bile-salt derivative used. However, with each of the photolabile derivatives the relative ratio of the labelling of the different membrane polypeptides was similar for both membrane subfractions. Provided that the uptake as well as the secretion of bile salts by hepatocytes are carrier-mediated processes, this suggests the participation of the same polypeptides in both processes.

Affinity Labels↗
PubMed1982

[Efficacy of nicorandil (SG-75), a substance with nitro-properties and long-term effects in coronary patients: improvement of LV-function and wall motility without pacing-induced myocardial ischemia].

Following trials in Japan, Nicorandil (SG-75) has been introduced as a new antianginal drug with coronary dilatory properties. The effects of 20 mg SG-75 administered sublingually were studied in 9 patients with coronary artery disease and reproducible pacing-induced myocardial ischemia (MIS) (rise in left ventricular enddiastolic pressure, changes in ST-segment, and angina). Changes in heart rate, arterial pressure and angiographic left ventricular ejection parameters, contractility, parameters derived from left ventricular function (ejection fraction, cardiac index, stroke work index) and cardiac work (left ventricular stroke work index, left ventricular work), myocardial oxygen consumption, cardiac efficiency (LVeff), and regional wall motion (RWM) were investigated for the following hemodynamic phases: 7th and 14th minute after SG-75, the immediate postpacing phase without medication (PPP), and the postpacing phase under the influence of SG-75 (PPP + SG). In the 7th and 14th minute after SG-75 and in the absence of stress, there was no variation from control values (p less than 0.05). In the 15th and 16th minute after SG-75 (serum-level control), under pacing stress equivalent to that measured in the PPP, the MIS observed in the absence of medication did not now occur. Moreover, in the PPP + SG-75 phase the following mean parameter changes were noted: ejection fraction +21%, cardiac index +37%, left ventricular stroke work index +48%, left ventricular work +52%, and LVeff +60%; RWM also improved. Prophylaxis of ischemia and improved hemodynamics under the influence of SG-75 were probably due to a decrease in preload (left ventricular enddiastolic pressure -41%) and afterload (stroke volume ratio -29%). Similar changes might have been expected after nitroglycerin, if given under equivalent conditions. Since no harmful effects, either subjective or objective, were apparent during or after application of SG-75, this seems to be a promising drug for the antianginal therapy of the future.

Aged↗
PubMed1982

[Mechanism and effects of the cardiotonic AR-L 115 BS in coronary heart disease: improved ventricular function and regional wall motility without angina pectoris].

UNLABELLED: The use of new cardiotonic drugs, such as AR-L 115 BS (ARL), in patients with coronary artery disease (CAD) might be limited by their aggravating myocardial ischemia (MIS). Accordingly, we investigated ARL's (2 mg/kg BW i.v.) hemodynamics, myocardial oxygen consumption (MVO2) and regional wall motion (RWM) in 30 patients with CAD presenting with pacing-induced MIS (angina, rise of LVEDP, lactate production). ARL improved LV-pump function in 13 group-1 patients (average increases: cardiac index by +25%; LV-work by +17%; dp/dtmax by +30%; coronary sinus flow by +39%), while there was a decrease in preload (LVEDP by -44%) and afterload (AOMP by -9%) and cardiac efficiency by -25%. Such ARL-effects required a rise of MVO2 by +41% but did not induce MIS. These beneficial results were corroborated by significant hemodynamic improvements also in 17 group-2 patients when comparing the non-medicated immediate post-pacing period (PPP) with MIS versus the ARL-medicated PPP (= PPP + ARL) without MIS, where RWM improved by an overall average of 26 +/- 11% in the phase PPP + ARL. CONCLUSION: In CAD ARL improves hemodynamics and RWM. The mechanism is pre- and afterload reduction, increase in contractility, MVO2 and CSF without MIS being induced.

Cardiotonic Agents↗
PubMed1981

Splintless microsurgical anastomosis of the ureter in the dog.

In an experimental study in dogs, four different techniques of microsurgical anastomosis using Vicryl 8-0, have been compared: 1. Interrupted submucosal sutures; 2. Continuous submucosal sutures; 3. Full thickness interrupted sutures; 4. Full thickness continuous sutures. Intravenous urography and electron microscopic studies three months post operatively showed that ureteric stricture had occurred in only 2 cases out of 24. Microsurgical techniques are recommended for ureteric anastomoses.

Animals↗
PubMed1981

A new non-glycoside, non-adrenergic cardiotonic agent AR-L 115 BS. Hemodynamic proof of its efficacy after both i.v. and oral administration.

In 11 patients with New York Heart Association (NYHA) functional class III-IV symptoms we monitored the effect of 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4.5-b]pyridine (AR-L 115 BS). Heart rate (HR), pulmonary arterial mean pressure (PAM), aortic systolic pressure (AoSP) and thermodilution cardiac output (CO) were measured before and up to 25 min after a bolus of AR-L 115 BS, 3 mg/kg body weight, i.v. The oral effect of AR-L 115, 200 mg, 3 times daily, was monitored in 18 patients with congestive cardiomyopathy (CC) over a period of 4 days. AR-L 115 BS is also orally active and thus is a very promising inotropic agent for the treatment of chronic heart failure in man.

Administration, Oral↗
PubMed1981

[Hemodynamics and metabolic-energetic expenses of the influence of AR-L115 in patients with coronary artery disease (author's transl)].

AR-L115 has been shown to substantially improve myocardial pump function in patients (pts) with advanced congestive cardiomyopathy by i.v. and by p.o.-route. Since AR-L115 effects on myocardial oxygen consumption (MVO2) and coronary blood flow (CSF) are unknown, the hemodynamic myocardial metabolic and ECG-responses to AR-L115 (2 mg/kg BW bolus) were monitored at the 9, 14 and 19-min interval in 7 patients coronary 3-vessel disease, exhibiting ischemia during pacing stress only. Maximal responses occurred at the 14th min after AR-L115. THere were (average) increases in cardiac index by 30%, in heart rate by 19%, in CSF by 39%, in MVO2 by 34%, and in dp/dt max by 27%. There were (average) decreases in peak systolic pressure by 13%, in PCW by 30%, in LVEDP by 42%, in systemic vascular resistance by 34%, and in coronary vascular resistance by 37%. All changes were significant (p less than 0.05). Unchanged (p greater than 0.05) remained myocardial lactate extraction, stroke work index, and stroke-index. The only moderate increase in MVO2 is possibly explained in that the increase in contractility was a least partially offset by the reductions in pre- and after load. The AR-L115-induced improved pump function was accompanied by moderate increases in MVO2 and CSF, but without evidence of myocardial ischemia.

Cardiac Pacing, Artificial↗
PubMed1980

The effect of increasing doses of ingested glucose on insulin and gastric inhibitory polypeptide (GIP) concentrations in man.

Gastric inhibitory polypeptide (GIP) is insulinotropic in vivo and in vitro. It is released following glucose ingestion and is a leading candidate as a mediator of the enteroinsular axis. To investigate the GIP response to increasing amounts of oral glucose, and its relationship to glucose levels and insulin secretion, fourteen normal volunteers ingested 25, 50 and 75 g of glucose at random with 5-7 days between each test. Serum insulin, glucose and GIP concentrations were measured and total integrated incremental responses were determined. Peak mean responses to glucose, insulin and GIP occurred at 30 min following each glucose ingestion. There were no significant differences in glucose concentrations at any interval with the varying glucose doses. Mean peripheral insulin concentrations were significantly increased after 50 or 75 g of glucose as compared with the 25 g dose (P less than 0.02). Mean GIP concentrations were significantly greater (P less than 0.03) between 15 and 180 min with both the 50 and 75 g glucose stimulus. Total integrated areas under the response curves for glucose, insulin and GIP showed a graded increase in circulating insulin and GIP (P less than 0.01) as the amount of ingested glucose was increased from 25 to 75 g. These findings show that increasing doses of glucose stimulated greater levels of GIP and insulin and further support the insulinotropic properties of endogenous GIP in man.

Administration, Oral↗
PubMed1980

Induction of prostaglandin E release from macrophages by colchicine.

Rat peritoneal macrophages released high amounts of prostaglandin E (PGE) when treated in vitro with 10(-7) to 10(-4) M colchicine. PGE production occurred after a lag period of 4 hr and proceeded at a constant rate for more than 24 hr. Lymphocytes could not be stimulated to PGE release by colchicine. Disaggregation of microtubules appeared to be an essential event, since lumicolchicine was inactive and addition of heavy water (D2O) abolished colchicine-induced PGE formation. Cytochalasin B (5 microgram/ ml) did not interfere with PGE production by colchicine during the initial 12 hr, but thereafter it gave rise to an activity capable of degrading or converting newly synthesized PGE. Although details of the mechanisms by which colchicine in association with disrupted microtubules may induce PGE release remain unclear, these observations suggest that components of the cytoskeleton may efficiently influence the biosynthesis of prostaglandins.

Animals↗
PubMed1980

[Echo parameters of chronic aortic regurgitation (author's transl)].

Staging and timing of aortic-valve replacement, with respect to long-term prognosis is crucial in patients with isolated chronic aortic regurgitation (AR). To compare angiographic and M-mode echocardiographic parameters we echoed 39 patients one day before cardiac catheterisation: The angiography was used to divide the collective into four grades (G I-G IV). End-diastolic volume (EDV), stroke volume (SV) and regurgitant volume (RV) were used as echo parameters of the left ventricular volume, ejection fraction (EF) and circumferential fiber shortening (VCF) as parameters of left ventricular function. AR of G II and G III could be differentiated by an increase of EDV from 145 +/- 28.2 to 304 +/- 33.5 ml (p < 0.001), whereas EDV in G I-G II were similar to normal and G IV was similar to G III. EF and VCF were able to differentiate G III and G IV by a decrease from 67 +/- 8% to 54 +/- 7% (p < 0.001) and 1.01 +/- 0.24 to 0.88 +/- 0.31 (p < 0.01) respectively. Thus echo measurements predicted AR greater than G II from an increase of the EDV by more than 110% and a regurgitant volume of more than 3 1/min. G III and G IV could be differentiated by EF und VCF. These quantitative echo parameters were highly sensitive (92%) and specific (96%) whereas all other M-mode echo signs (oscillations of the mitral valve leaflet and interventricular septum, amplitude of oscillations, aortic root diameter, diastolic separation of the cusps) could be used only as qualitative indices, some with high specificity. Echocardiography allows a non-invasive assessment of the severity of AR based on parameters of left ventricular volume and function and thereby assist the accurate timing of aortic valve replacement.

Adult↗