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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

Diurnal changes and reproducibility of corrected sinus node recovery time.

Corrected sinus node recovery time (CSRT) has been found unreliable in identifying all cases of sick sinus syndrome. Since other factors than sinus node dysfunction might add to the pathologic significance of the CSRT, we assessed it in 15 patients (nine group I patients with "prolonged" CSRT max = 3,196 + 2,740 msec and six group II patients with "short" CSRT max = 367 + 79 msec) at 0800, 1100, 1400, 1700, 2000, and 2300 hours with atrial overdrive stimulation rates (AST) of 90, 110, 140, 170, and 200 bpm on three consecutive days using a loop-mounted stable atrial electrode. Only with AST greater than or equal to 140 beats per minute (bpm) did all CSRTI values prove prolonged (greater than or equal to 560 msec). CSRTI values at corresponding time intervals were reproducible with AST greater than or equal to 140 bpm (day 1 vs 2 vs 3, P greater than .05), but not at AST 90 bpm and 110 bpm (P less than .05); CSRTII results, however, varied from day to day (less than .05) due to less scatter of single results. CSRTI results increased progressively with AST 90, 110, and 140 bpm from 301 + 256 msec by 60% for each pacing rate up to 785 + 848 msec. With AST greater than or equal to 140 bpm, the pattern of CSRT changes was inconsistent; this was also reflected by the distribution of the mean maxima of CSRTI: For 0800 hours at AST 140 bpm = 822 + 937 msec; for 1100 hours at AST 200 bpm = 824 + 1446 msec; for 1400 hours at AST 140 bpm = 780 + 814 msec; for 1700 hours at AST 170 bpm = 1,099 + 1,008 msec; for 2000 hours at AST 200 bpm = 1,156 + 1,280 msec; and for 2300 hours at AST 170 bpm = 1,021 + 1,102 msec. We conclude therefore that the optimal diagnostic yield for sick sinus syndrome testing is influenced by the time of the day and the AST used for CSRT testing.

Adult↗
PubMed1983

Effects of AR-L 115 BS (Sulmazol), a new cardiotonic agent, in coronary artery disease: improved ventricular wall motion, increased pump function and abolition of pacing-induced ischemia.

AR-L 115 BS (Sulmazol) is a new noncatechol, nonglycosidic cardiotonic agent. In 17 patients with significant coronary artery disease, the influence of AR-L 115 BS on hemodynamics and regional wall motion was investigated under the following conditions: 1) control, 2) the immediate postpacing period without medication, and 3) the postpacing period under the peak influence of AR-L 115 BS, 2 mg/kg intravenously. During the postpacing phase without medication, all patients developed ischemia (angina, ST segment alterations, increase of mean left ventricular end-diastolic pressure from 13 to 30 mm Hg), left ventricular pump function diminished and overall regional wall motion showed a tendency to decrease (p greater than 0.05). However, during the postpacing period with AR-L 115 BS medication, ischemia was abolished (no angina; mean left ventricular end-diastolic pressure decreased to 13 mm Hg; hemodynamic variables returned to control levels and left ventricular pump function showed some improvement while overall regional wall motion showed tendencies to improve. A comparison of alterations of hemodynamics and regional wall motion during the postpacing phase without medication with those under the influence of AR-L 115 BS shows that overall left ventricular pump function and regional wall motion improved while angina and an increase in left ventricular end-diastolic pressure were prevented. It is concluded that AR-L 115 BS improves left ventricular pump function and regional wall motion in coronary artery disease without inducing ischemia, probably by means of a reduction in extravascular resistance.

Angina Pectoris↗
PubMed1983

Macrophage-activating factors from different T cell clones induce distinct macrophage functions.

The data reported in this paper are the first demonstration that different T cell clones (PC-AKR-CI 96, clone 96; PK 7.1.2 E8, clone 7.1.2 E8) secrete different macrophage-activating factors (MAF) that induce distinct macrophage activities. Incubation of resident murine macrophages with MAF 7.1.2 E8 increased RNA, protein, and glycoprotein synthesis, hexosemonophosphate shunt (HMPS) activity, release of oxygen metabolites (O-2, H2O2), pinocytosis, phagocytosis, and tumor cytostasis, whereas no effect on prostaglandin E (PGE) release, schistosomula killing, and tumor cytolysis could be observed. In contrast, MAF 96 increased glycoprotein synthesis, HMPS activity, release of oxygen metabolites and PGE, schistosomula killing, and tumor cytostasis and cytolysis, whereas RNA and protein synthesis and pinocytosis were decreased and phagocytosis remained unaffected. Thus, MAF from both T cell clones share some macrophage-activating properties but differ in others. Most importantly, both MAF could be differentiated serologically by a rabbit anti-lymphokine antiserum that selectively inhibited MAF 96 but not MAF 7.1.2 E8 activity. At optimal concentrations, MAF 96 and 7.1.2 E8 were active in the absence of lipopolysaccharide (LPS) whereas LPS enhanced the activity of suboptimal doses of MAF 96 but not of MAF 7.1.2 E8. These data are discussed with respect to the possibility that the functional dichotomy of T cell clones might reflect different activities of normal T cell subpopulations.

Animals↗
PubMed1983

Photolabile derivatives of bile salts. Synthesis and suitability for photoaffinity labeling.

In an approach to the identification of bile salt-binding carriers, the photoactivable bile acid derivatives A) 3 beta-azido, 7 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oic acid, B) 7,7-azo-3 alpha,12 alpha-dihydroxy-5 beta-cholan-24-oic acid, and C) 11 xi-azido-12-oxo-3 alpha,7 alpha-dihydroxy-5 beta-cholan-24-oic acid were synthesized in unconjugated and taurine-conjugated form. Photolysis of the 3 beta-azido derivatives was studied using a light source with a maximum emission at 300 nm and established a half-life time of 18.5 min. The photochemistry of the 7,7-azo derivatives was investigated using light with a maximum at 350 nm and had a half-life time of 2.2 min. The 11 xi-azido-12-oxo derivatives were photolyzed with light having a maximum at 300 nm resulting in a half-life time of 8.5 min. The suitability of the 7,7-azo derivatives for photoaffinity labeling was demonstrated by photolyses in 14C-labeled methanol and acetonitrile. The generated carbene reacted with the solvents under covalent bond formation of 6 to 12%. The efficiency of all synthesized photolabile derivatives for photoaffinity labeling of bile salt binding proteins was demonstrated.

Affinity Labels↗
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↗