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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 415 records · Page 23Linked to original sources

Gin-mediated site-specific recombination in bacteriophage Mu DNA: overproduction of the protein and inversion in vitro.

Inversion of the G segment in bacteriophage Mu DNA occurs by a site-specific recombination event and determines the host specificity of Mu phage particles produced. Inversion is mediated by a Mu function (Gin). The gin gene has been placed under control of the inducible lambda pL promoter and a synthetic Shine-Dalgarno linker upstream of the initiation codon. The Gin protein content in induced cells is boosted to 10% of total protein. Partially purified extracts from overproducing strains promote efficient inversion of the G DNA segment in vitro which is visualized by agarose gel electrophoresis of the substrate DNA after cutting with appropriate restriction endonucleases. The in vitro reaction requires Mg, a super-coiled DNA substrate and occurs in the absence of exogenous ATP. Inversion from the G(+) to the G(-) orientation is as efficient as the switch from G(-) to G(+).

Journal Article↗

Suppression of high-grade ventricular ectopic activity by antiarrhythmic drug treatment as a marker for survival in patients with chronic coronary artery disease.

In order to investigate the relationship between the ease of suppression of complex (frequent multiform, repetitive, and early) ventricular premature beats (VPBs) and subsequent survival, 50 consecutive patients with chronic coronary artery disease (CAD) were followed retrospectively during a mean observation period of 16 months. A total of 124 drug trials were performed using single or combined class I, II, and III antiarrhythmic drugs. Thirty-nine patients were considered "responders" (elimination of Lown classes greater than or equal to IVa and reduction of greater than 30 multiform VPBs to occasional unifocal VPBs during Holter monitoring), whereas in 11 patients VPBs could not be adequately suppressed ("nonresponders"). There were no significant differences in age and congestive heart failure in the two groups. There were three deaths (one sudden) in the 39 "responders" but five deaths (three sudden) in the 11 "nonresponders" (p less than 0.01 for all deaths, p less than 0.05 for sudden deaths). Cumulative probability of survival at 12 months was 0.93 for "responders" and 0.64 for "nonresponders" (p less than 0.005). Significant side effects necessitated drug withdrawal in four patients. Our data suggest that survival in patients with CAD is better when complex VPBs can be suppressed.

Adult↗

Inhibition of the thrombin-platelet reaction by hirudin.

The influence of hirudin on the thrombin-platelet reaction was studied by determination of thrombin-induced serotonin release from blood platelets. The dissociation constant for the thrombin-hirudin complex calculated from data obtained by measuring the platelet reaction (Ki 50 pmol/1) was in accordance with the value obtained by determination of fibrinogen clotting. Prevention of the effect of thrombin on platelets required the addition of hirudin in at least 10-fold molar excess. The release of serotonin could be immediately stopped by hirudin at any time when the special conditions for the reaction of thrombin with the tight-binding inhibitor and the receptors on the platelet surface were taken into account.

Blood Platelets↗

[Activation of the fibrinolytic system with dehydrochlormethyltestosterone].

4-Chloro-1-dehydro-methyltestosterone (2 mg/kg/die) administered to rats and rabbits for three months increased the spontaneous fibrinolytic activity of blood, the release of plasminogen activator stimulated by venous stasis, and the activator activity in the kidney. Its effect in animal experiments corresponded to that of the steroid stanozolol tested for comparison.

Animals↗

[3H]dihydroergocryptine binding to alpha-adrenoceptors in human femoral veins and arteries.

In order to characterise subtypes of alpha-adrenoceptors in human vascular tissue, radioligand binding studies with [3H]dihydroergocryptine were carried out in human femoral veins and arteries. Binding of [3H]dihydroergocryptine to venous and arterial membranes was rapid and reversible reaching steady state within 4-6 min at 25 degrees C. [3H]Dihydroergocryptine was displaced from its receptor site on vascular membranes by unlabelled alpha-adrenoceptor agonists and antagonists in a concentration-dependent manner. Yohimbine and guanfacine which possess high affinity for alpha 2-adrenoceptors were more effective in competing for [3H]dihydroergocryptine binding sites in veins than in arteries. Prazosin and phenylephrine with high affinity for alpha 1-adrenoceptors were more effective displacers in arteries than in veins. The results suggest that the alpha-adrenoceptor population differs between human femoral veins and arteries. In veins, predominantly alpha 2-adrenoceptors are present, whereas in arteries the adrenoceptor of the alpha 1 type prevails. The results show that the uneven distribution of alpha 1- and alpha 2-adrenoceptors as has been found in animal experiments and pharmacological investigations with human vessels could also be demonstrated by binding studies with [3H]dihydroergocryptine in human femoral arteries and veins.

Adrenergic alpha-Agonists↗

Clinical evaluation of the St. Jude Medical heart valve prosthesis. A two-year follow-up of 150 patients.

To evaluate the clinical performance of the St Jude Medical bileaflet heart valve prosthesis, we followed 150 consecutive patients (95 male and 55 female patients, mean age 54 years, range 1 to 74 years) for an average of 24 months. These included 74 patients with aortic, 56 patients with mitral, and 20 patients with multiple valve replacement. During the 2 year follow-up, there were a total of four perioperative and seven late deaths, two of which were prosthesis related. Reoperation was necessary in four patients, because of paravalvular leaks in two patients with mitral and one patient with aortic prostheses and because of leaflet dislodgment in one patient with a mitral prosthesis, a postoperative complication that has not been reported previously. The thromboembolic rate per 100 patient-years was 2.6 in aortic and 2.9 in mitral valve replacement, the symptoms being reversible in all patients. All patients were receiving anticoagulant therapy. A total of four complications of anticoagulant therapy (three minor and one fatal) were observed. Significant hemolysis was observed in none of the patients. In patients with dyspnea, the New York Heart Association functional classification was 2.7 +/- 0.8 preoperatively versus 1.3 +/- 0.6 postoperatively. In patients with angina, it was 2.6 +/- 0.6 preoperatively versus 1.03 +/- 0.2 postoperatively. Noninvasive Doppler measurements revealed excellent flow characteristics, values being close to those obtained in natural valves (mean +/- standard deviation of maximal flow velocity: 1.5 +/- 0.5 versus 0.9 +/- 0.1 m/sec in the aortic position; 1.1 +/- 0.3 versus 0.8 +/- 0.3 m/sec in the mitral position).

Adolescent↗

Animal experiments on the enhancement of fibrinolytic potential by anabolic steroids.

In animal experiments the anabolic steroids 4-chloro-17 beta-hydroxy-17-methylandrosta-1,4-dien-3-one and 4-chloro-11 beta-hydroxy-17-methylandrosta-1,4-dien-3-one were tested for their ability to enhance fibrinolysis in comparison to stanozolol. After daily administration of 2 mg/kg for 12 weeks the anabolic steroids were found to enhance spontaneous fibrinolytic activity of blood, fibrinolytic capacity and tissue plasminogen activator activity in the kidneys of rats and rabbits. Concomitantly, the AT III activity of blood increased.

Animals↗

[Thrombin-stimulated release of serotonin from blood platelets].

The mechanism of platelet activation by thrombin was investigated using suspensions of human platelets. The assumption that the thrombin-platelet reaction shows characteristics of an agonist-receptor interaction was corroborated by an analysis of the relation between thrombin concentration and yield of 14C-serotonin secretion. However, silent thrombin binding sites that decrease the free thrombin concentration interfere with this interaction. When the influence of these binding sites is eliminated by a decrease in platelet concentration or by saturation with DIP-thrombin the concentration-response relationship can be interpreted by the adsorption isotherm of Langmuir. The binding sites interfering with the thrombin receptor interaction are identical with the high affinity binding sites of platelets. For the yield of secretion the velocity of thrombin addition is important. The platelet reaction decreases by slowing the rate of thrombin addition. In comparison with the reaction occurring at 37 degrees C, in that occurring at 0 degree C only the rate but not the yield of receptor stimulation is diminished. The results are in accordance with the assumption that the yield of platelet activation is determined by the equilibrium binding of thrombin. It is suggested that at 37 degrees C the processes of thrombin binding to the receptor, of receptor modification and of cellular response are immediately coupled with one another and that the rate-limiting step is the binding of thrombin to the receptor.

Blood Platelets↗

[Atypical and ischemic chest pain more than a year after aortocoronary bypass].

215 consecutive patients were followed up for more than a year (22 +/- 9 months) after aortocoronary bypass. Recurrence of ischaemic (anginal) and atypical chest pain was assessed: 54% of all patients were completely without pain postoperatively, 76% free of angina and 93% improved by at least one NYHA class. The frequency of severe atypical chest pain was similar pre- and postoperatively (11% and 13%, respectively), but nearly double that of postoperatively severe angina (13% vs 7%, P less than 0.05). Limiting atypical chest pains in patients with pre-operative atypical chest pain was much more frequent postoperatively than in patients who pre-operatively had only angina (30% vs 11%, P less than 0.005). These two patient groups did not differ with respect to age, sex, degree of vessels disease, exercise-induced ischaemia or number and patency of bypasses. Thus, exercise-limiting atypical chest pain can influence the surgical results in up to 30% of patients with pre-operative atypical chest pain (with or without typical angina).

Adult↗

[Are swimming and sauna hazardous in the rehabilitation of heart patients?].

The incidence of cardiac arrhythmias and ischemic episodes (I) during swimming and sauna as compared to other types of physical exercise was studied in 18 patients with coronary disease and in 18 controls without heart disease (mean age 46 and 48 years respectively). Maximum achieved heart rates during swimming and sauna were lower by at least 10% than those achieved during bicycle ergometry. Angina and/or ST segment displacement greater than or equal to 1 mm and frequent (greater than 1/min), multiform or repetitive VPB's occurred more frequently in coronary patients than in controls (I: 50 vs 11%, VPB's: 72 vs 28%, both p less than 0.005). VPB's were observed in 13/18 coronary patients, 6 of whom had these VPB's during swimming or sauna. Repetitive VPB's did not occur during swimming, but occurred during sauna in 2 coronary patients in whom they were also present during rest and walking. Ischemic episodes were noted in 9/18 coronary patients in 5 of whom they occurred during swimming. No ischemias were noted during sauna. It is concluded that swimming and sauna may safely be recommended during rehabilitation of coronary patients provided a submaximal exercise test and possibly a 24-h Holter ECG are performed on entry to exclude patients at risk.

Adult↗

Evaluation of systolic murmurs by Doppler ultrasonography.

Non-invasive continuous and pulsed wave Doppler ultrasonography was performed in 102 consecutive patients with clinically ill defined systolic murmurs to differentiate between flow murmurs, mitral regurgitation, aortic stenosis, and ventricular septal defect, as well as to assess the severity of aortic stenosis. Diagnoses with the Doppler method were based on velocity, direction, and duration of flow signals and were subsequently verified by cardiac catheterisation in all patients. Multiple evaluations were made in 31 patients. Sensitivity and specificity were 0.87 and 0.77 in mitral regurgitation, 0.9 and 1.0 in aortic stenosis, and 1.0 and 1.0 in ventricular septal defect. In 67 patients the estimation of severity of aortic stenosis using the Doppler technique to calculate aortic pressure gradients from maximum flow velocity was significantly correlated with that determined at catheterisation. It is concluded that Doppler ultrasonography is a highly useful technique for the non-invasive evaluation of clinically ill defined systolic murmurs.

Adult↗