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Biomedical subjects

W Kramer

Publications and source records attributed to W Kramer.

At least 127 records · Page 7Linked to original sources

Analysis of the efficacy of the new cardiotonic agent TA-064.

TA-064 is a new cardiotonic agent which is also effective orally, according to investigations conducted in Japan. We analyzed computer-assisted alterations of pressure-volume relationships serially and of indirect myocardial oxygen consumption (MVO2) estimations on line during TA-064 influence in 16 patients with congestive cardiomyopathy: left ventricular function was moderately decreased in seven patients (group A) and drastically decreased in nine (group B). Results showed that TA-064, 8 micrograms/kg/min intravenously, exerted positive inotropic effects in both groups and induced mean maximal delta percentage changes at about 5 minutes of infusion as follows: left ventricular stroke work index +65% and +47%; dP/dtmax +61% and 59%; left ventricular efficiency +62% and 53%; MVO2 +31% and +11% (p less than 0.05). TA-064, 20 mg by mouth induced serum levels (group A = 23.8 +/- 12ng/ml and group B = 26.4 +/- 20 ng/ml) corresponding to the effects with dosages of 1 to 2 ng/kg/min intravenously (p greater than 0.05), thus implying that significant changes in left ventricular function require higher oral dosages. We conclude that TA-064 improves left ventricular function, primarily via a contractility increase, also in group B patients without toxic side effects. On-line indirect MVO2 assessment and analysis of serial pressure-volume relationships helped to provide a more complex definition of the mechanism and efficiency of the cardiotonic agent under study.

Administration, Oral

Progressive cardiac involvement by Fabry's disease despite successful renal allotransplantation.

Enzyme replacement by renal allotransplantation has been suggested as a specific mode of therapy for Fabry's disease. We report a case of Fabry's disease who developed symptoms and signs of heart failure despite successful renal transplantation 14 years ago. Echo- and angiocardiographic features resembled findings in patients with hypertrophic non-obstructive cardiomyopathy. Endomyocardial biopsy specimens demonstrated cardiac manifestation of Fabry's disease.

Biopsy

Dialysis-induced cardiac arrhythmias: fact or fiction? Importance of preexisting cardiac disease in the induction of arrhythmias during renal replacement therapy.

Frequency and grade of premature ventricular depolarizations were assessed in 10 patients on maintenance renal replacement therapy. All medication was withdrawn prior to the study. Each patient was treated sequentially by 8 different methods [acetate and bicarbonate hemodialysis (HD), hemofiltration, hemodiafiltration, ultrafiltration, use of 5 different membranes]. Despite marked changes in serum electrolyte concentrations there was no difference in frequency or grade of premature ventricular beats between the periods before, during, and after renal replacement therapy. Comparison of the 8 methods tested revealed no superiority of 1 method during the observation period of 192 h for each patient. In a second group of 8 patients with confirmed coronary artery disease, acetate HD had no effect on grade and frequency of ventricular arrhythmias, although arrhythmias occurred more often (p less than 0.05) and were more dangerous. We therefore conclude that the incidence of ventricular arrhythmias is primarily dependant on the presence of preexisting coronary artery disease and that HD or related methods do not increase the risk of ventricular ectopies in patients without digitalis medication.

Adult

[Acute post-traumatic cholecystitis. Caused by or following polytrauma?].

Traumatic acute cholecystitis is of secondary importance beside many other complications in the polytraumatised patient, since it is rarely diagnosed--possibly too rarely. Difficulties often arise because of a multitude of injuries, which are often life-threatening and which must be given top priority (3). Men are chiefly involved (4). In most cases, the condition is preceded by shock, but not necessarily by gallstones (10, 11). First pointers in literature were given by Mennenga (8). As early as 1939 he pointed out that blunt abdominal trauma may produce tears in the gallbladder and bile duct regions. Marre (7) described acute signs in the upper abdomen due to rupture of the bile duct. Genesis of post-traumatic acute cholecystitis is still unclarified. Apart from rupture or perforation of the gallbladder or bile ducts, it is mainly shock (4, 9, 12) which is considered to be an important causative factor.

Abdominal Injuries

The gapped duplex DNA approach to oligonucleotide-directed mutation construction.

A simple and efficient method is described to introduce structurally pre-determined mutations into recombinant genomes of filamentous phage M13. The method rests on gapped duplex DNA (gdDNA) molecules of the phage M13 genome as the key intermediate. In this gdDNA, the (+) and the (shorter) (-) strand carry different genetic markers in such a way, that a rigorous selection can be applied for phage carrying the markers of the (-) strand. For introduction of the mutation, a synthetic oligonucleotide with partial homology to a target site within the single stranded DNA region is annealed to the gdDNA. The oligonucleotide subsequently becomes part of the (-) strand by enzymatic DNA gap filling and sealing. This physical linkage is preserved at the genetic level after transfection of a recipient E.coli strain deficient in DNA mismatch correction, so that the synthetic marker can be selected from the phage progeny independent from its potential phenotype. It is demonstrated that by this method mutants can be constructed with marker yields in excess of 70%.

Coliphages

Different base/base mismatches are corrected with different efficiencies by the methyl-directed DNA mismatch-repair system of E. coli.

The efficiency of methyl-directed DNA mismatch-repair of E. coli acting in vivo on heteroduplex genomes of phage M13 was found to be strongly dependent on the nature of the base/base mismatch to be corrected. Three efficiency classes were characterized:high (T/G, C/A and G/G); intermediate (A/A); and low (G/A, A/G, T/T, C/C, C/T and T/C). Methyl-directed DNA mismatch repair was lost completely for any type of mismatch in strains carrying either mutL or mutS mutations. Data obtained with a mutH mutant suggest that this locus is involved in methyl-dependent DNA strand discrimination. A functional correlation is suggested between the differential repair efficiencies and the frequencies of the corresponding replication errors.

Base Composition

Identity of hepatic membrane transport systems for bile salts, phalloidin, and antamanide by photoaffinity labeling.

Phalloidin, a bicyclic heptapeptide, and antamanide, a monocyclic decapeptide from the poisonous mushroom Amanita phalloides, interact with bile-salt-binding polypeptides of the hepatocyte membrane, as demonstrated by photoaffinity labeling using the photolabile bile salt derivative 7,7,-azo-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid, either unconjugated or taurine conjugated. With the photolabile derivatives of phalloidin, N-delta-(4-[(1-azi-2,2,2-trifluoroethyl) benzoyl]-beta-alanyl)-delta-aminophalloin, (N epsilon-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]lys6)-anta manide, the same membrane polypeptides with apparent MrS of 54,000 and 48,000 were labeled as with the photolabile derivatives of unconjugated and conjugated bile salts. The presence of bile salts decreased markedly the extent of labeling of these phalloidin- and antamanide-binding polypeptides. These results indicate that hepatic uptake systems for bile salts, phallotoxins, and the cycloamanide antamanide are identical, thus explaining the organotropism of phallotoxins.

Affinity Labels

[Microsurgery of the kidney pelvis].

In an animal experiment, excellent results were obtained using both microsurgical mucosa and all-layer, single-knot polyglactin (8/0 Vicryl) suture of the ureter. These results motivated clinical use of this microsurgical operative technique on five infants (4-9 months of age) with stenosis of the pelvis outlet. Both the microsurgical and suture techniques are equally suitable for plastic surgery of the renal pelvis, particularly with small anatomical conditions. However, all-layer suture carried out with magnifying lenses seems to be the simpler method, as the 8/0 Vicryl suture used becomes completely epithelialized intraluminally within a short period of time.

Humans

[Effects of the new cardiotonic agent TA-064: serial computer-assisted analyses of pressure-volume relations and online myocardial 02 consumption].

UNLABELLED: According to investigations conducted in Japan, TA-064 is a new cardiotonic agent, which is also effective orally. We analyzed computer-assisted alterations of pressure-volume relations serially and of MVO2 online (Bretschneider) during TA-064 influence in 16 patients with congestive cardiomyopathy: LV-function of 7 patients was only moderately decreased (group A) and in 9 patients massively (group B). RESULTS: 1) TA-064, 8 micrograms/kg/min, i.v. had positive inotropic effects in both groups and induced mean maximal delta% changes at about the 5th minute of infusion as follows: LVSWI + 65% and 47%; DP/DTmax + 61% and 59%; LV-efficiency + 62% and 53%; MVO2 + 31% and + 11% (p less than 0.05). 2) TA-064, 20 mg p.o. induced serum levels (A: 23.8 +/- 12 and B: 26.4 +/- 20 ng/ml) corresponding to the effects with the dosages 1-2 micrograms/kg/min, i.v. (p greater than 0.05), thus implying that significant changes in LV-function require higher p.o. dosages. 3) TA-064 i.v. on the 6th day of exposure to the medication produced less LV-function improvement than on day 1 (p greater than 0.05). CONCLUSIONS: In both groups A and B TA-064 improves LV-function primarily via increased contractility, without toxic side effects. For a more complex definition of the efficiency and mechanism of cardiotonic agents, the validity and importance of using on-line MVO2 assessment and analysis of serial pressure-volume relations is stressed.

Adult

Influence of fluid removal rate during hemodialysis on left ventricular performance and exercise tolerance in patients with coronary artery disease.

The effect of hemodialysis (HD) on left ventricular (LV) function and exercise tolerance were measured at rest and during exercise using gated equilibrium radionuclide ventriculography in seven patients with confirmed coronary artery disease (CAD). To separate the effects of fluid removal rate on LV function in CAD, we investigated the same patients with identical overall volume loss of 4 liters during two different treatment times (4 hr and 2 hr). HD significantly increased resting LV ejection fraction (EF) from 55.7 +/- 8% to 64.7 +/- 8% (P less than 0.01) during the 4 hr HD and from 58.1 +/- 9 to 68.1 +/- 10 (P less than 0.05) during the 2 hr HD. Indicating ischemia, EF decreased at pre- and postdialysis peak exercise without differences between both treatments. HD also resulted in an improved segmental wall motion score. Exercise duration as well as S-T segment depression and angina score improved during HD, whereas heart rate, blood pressure and double product remained unchanged. We conclude that HD improves global and regional resting LV function and exercise tolerance in patients with CAD. The degree of interdialytic hydration and not the degree of fluid removal per time affects LV performance in CAD. Since LV function is the major prognostic factor in CAD, those patients require volume restriction and/or shorter interdialytic phases.

Adult

[Complete revascularization surgery in patients with coronary disease with severely reduced left ventricular function. Discrepancies in the evaluation of results].

Clinical data, function and compliance of left ventricle as well as regional wall motion were analysed in 17 patients with preoperatively limited left-ventricular function and signs of myocardial ischaemia after complete revascularisation surgery. Recatheterisation after 5.2 months on average after surgery showed improvement by one NYHA class, an increase of mean left-ventricular enddiastolic pressure, which was interpreted as "improved status of ischaemia", a decrease of left-ventricular compliance by 30%, of enddiastolic volume by 14% and of endsystolic volume by 20% (P less than 0.05). Loss of function occurred in 3 out of 92 bypasses. Up to the time of reporting, 22.4 months postoperatively, all patients have survived in a relatively satisfactory clinical state. All parameters of left-ventricular function as well as regional wall motion showed a tendency for improvement after surgery in the majority of patients. However, pre- and postoperative mean values were not significantly different (P greater than 0.05). Thus, despite clearcut improvement of clinical state and "ischaemia index", improvement of left-ventricular function and regional wall motion are not consistently demonstrable. The reasons of this discrepancy cannot be ascertained by this investigation. The quality of the surgical intervention and the sensitivity of parameter assessment cannot be held responsible.

Blood Pressure

Inhibition of bile salt transport in brush-border membrane vesicles from rat small intestine by photoaffinity labeling.

The uptake of photolabile bile acid derivative, (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24 oyl)-2-aminoethanesulfonate (7,7-azo-TC), was investigated in rat ileal brush-border membrane vesicles. The uptake of 7,7-azo-TC showed a transient vesicle to medium ratio greater than one in the presence of a Na+ gradient. The Na+-dependent uptake of 7,7-azo-TC was inhibited by taurocholate and vice versa. 130 microM 7,7-azo-TC inhibited Na+-dependent taurocholate uptake by 50%. The degree of inhibitory power on taurocholate uptake was taurodeoxycholate greater than cholate greater than 7,7-azo-TC. Photoaffinity labeling of membrane vesicles with 7,7-azo-TC irreversibly inhibited Na+-dependent taurocholate and D-glucose transport but not Na+-dependent L-alanine transport. Kinetic and photoaffinity labeling experiments indicate that this representative photoaffinity probe interacts with the ileal Na+, bile salt cotransporter and may be used to identify polypeptide components of this transport system.

Affinity Labels

Bile salt-binding polypeptides in brush-border membrane vesicles from rat small intestine revealed by photoaffinity labeling.

Photoaffinity labeling of small intestinal brush-border membrane vesicles with photolabile bile salt derivatives was performed to identify bile salt-binding polypeptides in these membranes. The derivatives used in this study were the sodium salts of 7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid, 3 beta-azido-7 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-oic acid, their respective taurine conjugates, and (11 xi-azido-12-oxo-3 alpha, 7 alpha-dihydroxy-5 beta-cholan-24-oyl)-2-aminoethanesulfonic acid. With ileal brush-border membrane vesicles, photoaffinity labeling resulted in the identification of 5 polypeptides with apparent molecular weights of 125,000, 99,000, 83,000, 67,000, and 43,000. The extent of labeling depended on the photolabile derivative employed. In jejunal brush-border membrane vesicles, polypeptides with apparent molecular weights of 125,000, 94,000, 83,000, 67,000, and 43,000 were labeled. The results indicate that the binding polypeptides involved in bile salt transport in ileal brush-border membrane vesicles are 1) similar with one exception to those concerned with bile salt transport in jejunal brush-border membranes, and 2) markedly different from those previously shown to be concerned with bile salt transport in plasma membranes of hepatocytes.

Affinity Labels

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