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Biomedical subjects

P Stulz

Publications and source records attributed to P Stulz.

At least 19 recordsLinked to original sources

[Possibilities and limitations of surgical therapy in acute and chronic heart failure].

Five out of the many scenarios for surgical interventions in manifest or imminent heart failure that are of special importance for the practitioner as well as the attending physician are covered. In the context of acute heart failure, mechanical complications of infarction and acute aortic insufficiency in the course of infectious endocarditis are discussed. In a second part, heart failure in chronic regurgitation of the aortic valve and chronic ischemic heart disease are treated. Main attention is given to medical indication for surgical intervention.

Acute Disease

[Role of antibiotics in surgically treated active endocarditis].

In a retrospective study of 30 patients in whom a valve was replaced during active endocarditis, the role of the concomitant antimicrobial therapy was analyzed. In 75% of the patients with less than 1 week of adequate treatment before surgery, but only in 13% (p less than 0.001) with at least 1 week of therapy, could the microorganism be cultivated from the excised valve. Patients with bacteria on the valve had a 4-fold increased risk for prosthetic valve endocarditis and 2.7-fold more frequent paravalvular leakage. Therefore, in the absence of severe cardiac failure, the valve replacement should not be performed before the second week of therapy. Patients in whom microorganisms can be cultivated from the valve need a complete postoperative course of antimicrobial therapy.

Adult

Cell cultures from cryopreserved human lung tissue.

To assess gene induction in primary human fibroblasts, we have developed a method for cryopreservation of lung biopsies in liquid nitrogen. Fresh biopsies (n = 10) were chopped into 5 x 5 mm pieces and transferred into an ice-cold freezing medium. Biopsies were kept on ice for 15 min, followed by further cooling of the tissue to -70 degrees C. With this method, lung biopsies were preserved for more than 1 year before they were used for generating cell cultures. There was no significant difference in the biological responsiveness of fibroblasts generated from immediately cultured lung biopsies compared with those from cryopreserved tissue. The doubling rate of fibroblasts from fresh tissue was 23.6 +/- 1.1 hr; compared to 23.5 +/- 1.5 hr for fibroblasts generated from cryopreserved tissue. PDGF-BB enhanced de novo synthesis of DNA 100 times, in both the immediately cultured fibroblasts and those generated from cryopreserved biopsies. Macrophages, dendritic cells and endothelial cells could also be recovered from cryopreserved lung tissue. This method permits long-term storage of lung tissue and the possibility of establishing primary cell lines from the same tissue at later times without appreciable changes in their cellular biological characteristics.

Cell Cycle

Different effects of activated platelets in the right gastroepiploic and internal mammary arteries. Implications for coronary artery grafting.

The right gastroepiploic artery is increasingly utilized as an alternative coronary bypass conduit, although postoperative spasm can represent a problem. Platelet-vessel wall interactions are important determinants of graft function and patency. We studied the effects of activated platelets in porcine and human gastroepiploic and mammary arteries. Arterial rings were suspended in organ chambers for isometric tension recording. In the porcine and human gastroepiploic arteries with or without endothelium contracted with norepinephrine, activated platelets evoked only further and strong contraction. In contrast, in the porcine and human mammary arteries, endothelium-dependent relaxations to platelets mediated by nitric oxide were noted, particularly in rings preincubated with the thromboxane A2 receptor antagonist SQ-30741 and the 5-hydroxytryptamine (5HT2)-serotonergic receptor antagonist ketanserin. Although endothelium-dependent and endothelium-independent relaxation to bradykinin and the nitrovasodilator 3-morpholino sydnonimine were more pronounced in the gastroepiploic than in the mammary artery, norepinephrine, serotonin, and potassium chloride evoked much stronger contractions in the former than in the latter. Thus activated platelets induce pronounced contraction of the gastroepiploic artery that may contribute to postoperative spasm. The administration of antiplatelet drugs and vasodilators that prevent the effects of thromboxane A2 and serotonin may be beneficial for gastroepiploic graft function.

Adenosine Diphosphate

[Traumatic aortic rupture--an emergency indication?].

On the basis of a retrospective analysis that included 22 patients with traumatic rupture of the thoracic aorta, the appropriate time for surgical intervention will be evaluated. The patients were divided into two groups according to their clinical status at the time of surgery. Seven patients with unstable vital systems underwent immediate surgery; 5 out of 7 died intraoperatively. Because of either the surgeons decision or delayed diagnosis, 15 patients underwent surgical repair of the aorta after various time intervals; 3 of these expired late after the operation. These results indicate that the timing of surgical intervention in the stable covered aortic rupture with serious associated injuries should preferably be deferred until after the patients condition has stabilized.

Aorta, Thoracic

Allelic loss on the short arm of chromosome 11 in non-small-cell lung cancer.

Forty-eight samples of primary non-small-cell lung cancer (NSCLC) and normal tissue from the same patients were analyzed for allelic deletions on chromosome 11p. Five polymorphic loci were assessed to determine the incidence of 11p sequence deletions and to define hot-spots of deletions. Information was obtained from all patients in at least one locus. Our data show that the deletions observed were not randomly scattered over the short arm of chromosome 11. Rather, 2 hot-spots of deletions were observed: one in the area of the genes for catalase and beta-FSH corresponding to band 11p13, the other close to the IGF-II locus corresponding to band 11p15. A high incidence of loss of heterozygosity (LOH) was found with the probe for catalase (21/29), a locus flanking the centromeric region of the Wilms' tumor locus. Most of the samples exhibiting LOH of one or more of the alleles analyzed remained heterozygous for at least one other chromosome 11p allele. Furthermore, duplication of the intensity of the remaining allele was rarely observed. Our results indicate that LOH on the short arm of chromosome 11 is a common event in NSCLC and that the chromosomal region containing the Wilms' tumor locus is most commonly involved.

Alleles

Different interactions of platelets with arterial and venous coronary bypass vessels.

We studied the interaction of platelets with the wall of human internal mammary arteries and saphenous veins, suspended in organ chambers for measurement of isometric tension. Vessels were obtained during coronary bypass surgery and cut into 5 mm rings; in some the endothelium was chemically removed. Rings from several patients were randomly chosen for each experiment, and in each ring six concentrations of platelets (from healthy blood donors; 1-75 x 10(3)/microliters) were tested consecutively and concentration-response curves constructed; the areas under these curves were used for statistical comparisons. In rings of internal mammary artery contracted in response to noradrenaline, aggregating platelets induced endothelium-dependent relaxation which was prevented by apyrase (0.67 U/ml ADPase activity) and L-NG-monomethylarginine (1 mmol/l). By contrast, in saphenous vein rings contracted in response to noradrenaline, aggregating platelets induced only a further increase in tension. In quiescent vessels, the platelet-induced contraction did not occur in arteries with endothelium but that in veins was greater and facilitated by endothelium. Preincubation of platelets with aspirin (10 mumol/l) reduced the contraction in both vessels, but contraction was abolished only in the presence of both the thromboxane receptor antagonist SQ-30741 and the serotoninergic (5HT2) receptor antagonist ketanserin. These findings show that platelet-derived ADP causes release of nitric oxide by the endothelium of internal mammary artery but not of saphenous vein; thromboxane A2 and serotonin mediate contraction in vein but not artery with endothelium. These differences may contribute to differences in graft function and the clinical efficacy of antiplatelet drugs.

Apyrase

Decision-making aspects in the timing of surgical intervention in aortic rupture.

Twenty-one consecutive patients with traumatic rupture of the thoracic aorta were treated at the University Hospital of Basel, Switzerland. The patients were divided into two groups according to their clinical status at the time of surgery. Six patients with unstable vital functions underwent immediate surgery (group 1), while 15 patients were operated upon semi-urgently because of delayed diagnosis or electively (group 2). Five of 6 patients undergoing immediate repair in group 1 died intraoperatively, 3 of 15 patients with deferred surgery expired postoperatively after a period of 6 weeks to 3 months. All 13 survivors underwent follow-up for 10 months to 20 years. NMR imaging of the aorta in 12 patients revealed neither pseudoaneurysms nor stenosis at the anastomoses. The results indicate that the timing of the surgical intervention in stable contained aortic rupture with serious associated injuries should preferably be deferred until after stabilization of the clinical status.

Adolescent

Unusual localisation of a pulmonary hamartoma.

Hamartomas of the lung are usually located within the pulmonary tissue and sometimes within the bronchus. In this paper the rare case of a pedunculated epipleural hamartoma causing site-dependent chest pain is presented.

Female

Different activation of the endothelial L-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein.

The endothelium releases substances controlling vascular tone and platelet function. We investigated mediators of endothelium-dependent responses in human internal mammary arteries and saphenous veins. The inhibitor of nitric oxide formation, NG-monomethyl L-arginine, enhanced the sensitivity to norepinephrine (fivefold) and evoked more pronounced endothelium-dependent contractions in internal mammary arteries (19 +/- 6% of 100 mM KCl) than in saphenous veins (2 +/- 1%; p less than 0.005). In internal mammary arteries, NG-monomethyl L-arginine, but not indomethacin, markedly reduced endothelium-dependent relaxations to acetylcholine (from 95 +/- 2% to 39 +/- 7%; p less than 0.005) and prevented those to histamine (78 +/- 6% to 4 +/- 3%; p less than 0.005). In saphenous veins, endothelium-dependent relaxations to acetylcholine were weak (24 +/- 11%), while nitric oxide caused comparable relaxations (85 +/- 3%) as in internal mammary arteries (80 +/- 5%; NS). NG-Monomethyl L-arginine prevented the relaxations to acetylcholine and unmasked endothelium-dependent contractions (30 +/- 10%). Indomethacin and the thromboxane synthetase inhibitor CGS-13080 augmented relaxations of saphenous veins to acetylcholine from 24 +/- 11% to 46 +/- 9% (p less than 0.05). Histamine-evoked contractions were converted to endothelium-dependent relaxations by indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ-30741 (38 +/- 3% and 40 +/- 6%; p less than 0.05) but not CGS-13080. Thus, 1) nitric oxide mediates endothelium-dependent relaxations in human arteries and veins; 2) internal mammary arteries release more nitric oxide than do saphenous veins, and 3) in saphenous veins, the effects of nitric oxide are reduced by endothelium-derived contracting factors originating from the cyclooxygenase pathway.

Acetylcholine

[Traumatic ruptures of the thoracic aorta].

The authors present a group of 22 patients admitted for traumatic rupture of the thoracic aorta between 1969 and 1989. Most of them were polytraumatized patients (mean ISS 45). The majority of the injured patients possibly died before arriving at hospital. Amongst the other patients, there was a local tamponade of the hemorrhage. The risk of rupture of the patients arriving alive at the hospital is consequently restricted. The mortality of the patients operated in shock is high (3/4). The authors recommend to operate these lesions in delayed emergency.

Adult

Prevention of aortocoronary vein bypass graft occlusion: which antithrombotic treatment and for how long?

The effects of 50 mg aspirin combined with 400 mg dipyridamole were compared with those of standard anticoagulant therapy, in the prevention of aortocoronary vein bypass graft occlusion. Early graft occlusion in 249 patients, with 749 distal vein graft anastomoses, were angiographically assessed 11.5 +/- 2 days after surgery and were almost equal in both treatment groups. In half of the patients in each group, active treatment was replaced by placebo after 3 months. Repeat angiography after 1 year (360 +/- 24 days) showed that more new late graft occlusions occurred in patients with only 3 months active medication (either regimen). The incidence of major complications was significantly higher in patients treated with anticoagulants, with minor side-effects more common in the antiplatelet group. Thus, this antiplatelet drug regimen was as effective as standard anticoagulant therapy in the prevention of early and late bypass graft occlusion, but carried a significantly lower risk of severe complications. In addition, as replacement of active treatment by placebo after 3 months resulted in significantly more graft occlusions, antithrombotic treatment should be continued for at least one year after coronary artery bypass graft surgery.

Adult

Tricuspid valve endocarditis in the drug addict: a reconstructive approach ("vegetectomy").

This report describes the case of a 24-year-old female heroin addict with large tricuspid valve vegetation, recurrent septic pulmonary emboli, and renal failure, due to immune-complex nephritis. The clinical course was initially complicated by acute hepatitis A. Because of recurrent emboli and persistent fever despite adequate antibiotic therapy she underwent excision of the vegetation ("vegetectomy") and tricuspid valvuloplasty. She was well at follow-up 12 months later with trivial tricuspid regurgitation shown by doppler-echocardiography. Kidney and liver function were normal. Right-heart endocarditis in drug addiction and therapeutic approaches are discussed. In selected cases "vegetectomy" and valvuloplasty offer a promising therapeutic alternative.

Adult

Heart valve replacement with the Björk-Shiley and St Jude Medical prostheses: a randomized comparison in 178 patients.

In 178 patients, a randomized prospective comparison between the 60 degrees spherical disc Björk-Shiley (BS) and the St Jude Medical (SJM) heart valve prostheses was performed. Four-week perioperative mortality was zero in the BS (n = 84) and 4.3% in the SJM group (n = 94). During a mean (+/- SD) follow-up of 52 +/- 20 months or 778 patient-years, late cardiac mortality per year was 2.4% in the BS and 2.2% in the SJM group. The yearly thromboembolic rates were 1.4% in the BS and 2.0% in the SJM group. There was no mechanical valve failure or haemolytic anaemia. Paravalvular leaks and major bleeding complications occurred at low rates in both groups (1.1% and 2.2% per year in BS; 0.7% and 1.7% per year in SJM). Functional results were similarly good with 96% of patients with BS valves and 95% of patients with SJM prostheses being in NYHA classes I and II, respectively. We conclude that heart valve replacement with mechanical prostheses can be performed with equally good results using either the Björk-Shiley spherical disc valve or the St Jude Medical bileaflet prosthesis.

Aged

Different mobilization of calcium in endothelin-1-induced contractions in human arteries and veins: effects of calcium antagonists.

We studied the role of extra- and intracellular Ca2+ in endothelin-1-induced contractions of the isolated human internal mammary artery and vein. Veins were more sensitive to the peptide than arteries (concentration shift:3.2-fold; n = 4-10, p less than 0.05). The Ca2+ antagonists darodipine, verapamil, and diltiazem (10(-7)-10(-6) M) did not prevent the response to endothelin-1 in both vessels. In contrast, darodipine (10(-8)-10(-6) M), added after the contraction had developed, partially reversed the response in the artery (26 +/- 7%) and particularly in the vein (67 +/- 5%; n = 4, p less than 0.005 compared to the artery). Removal of extracellular Ca2+ reduced the contractions to endothelin-1 (10(-8) M) in the artery (control: 89 +/- 4% of 100 mM KCl; Ca2(+)-free: 68 +/- 4% n = 4-6, p less than 0.01), but not in the vein except at low concentrations (10(-9) M) of the peptide. After removal of intracellular Ca2+ with caffeine in the artery, endothelin-1 still evoked a contraction (17 +/- 3%, n = 3; p less than 0.005 vs. control), while in the vein the response was abolished. Thus, mobilization of Ca2+ during endothelin-1-induced contractions differs in the human internal mammary artery and vein. In the artery, the contraction depends on extracellular Ca2+, intracellular caffeine-sensitive Ca2+ stores, and a caffeine-insensitive component, while in veins, mobilization of intracellular Ca2+ is most important. Ca2+ antagonists do not prevent, but partially reverse, endothelin-1-induced contractions indicating that voltage-operated Ca2+ channels do not initiate but contribute to the maintenance of the response.

Caffeine

Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm?

Endothelin-1 is an endothelium-derived vasoconstrictor peptide. Its circulating levels are below those known to evoke direct vascular effects. To study whether low concentrations of endothelin-1 potentiate the effects of other vasoconstrictor hormones, we suspended isolated human internal mammary and left anterior descending coronary artery rings in organ chambers for isometric tension recording. In mammary artery rings, the contractions to norepinephrine (3 x 10(-8) M) were potentiated by threshold (3 x 10(-10) M) and low concentrations (10(-9) M) of endothelin-1 (96 +/- 35% and 149 +/- 58% increase from control; p less than 0.01 and 0.001; n = 6). The inhibitor of endothelial nitric oxide formation L-NG-monomethyl arginine did not affect the potentiating effects of the peptide. The calcium antagonist darodipine (10(-7) M) prevented the potentiation of the response to norepinephrine evoked by endothelin-1. Similarly, contractions to serotonin (10(-7) or 3 x 10(-8) M) were amplified by endothelin-1 (3 x 10(-10) M) in the mammary (30 +/- 9%) and in the coronary arteries (59 +/- 25%). Endothelin-1 (10(-9) M) further potentiated the response (57 +/- 23% in mammary and 87 +/- 26% in coronary arteries; p less than 0.05; n = 7 and 3). The sensitivity of mammary arteries to calcium chloride was markedly enhanced in the presence of endothelin-1 (3 x 10(-10) M; concentration shift, eightfold; p less than 0.01; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries

Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins.

Endothelin-1 is a 21-amino acid endothelial vasoconstrictor peptide that may be the physiological antagonist of endothelium-derived relaxing factor (EDRF). Endothelin-1 (10(-11)-3 x 10(-7) M) evoked potent contractions of isolated internal mammary arteries, internal mammary veins, and saphenous veins, which were enhanced in internal mammary veins as compared with internal mammary arteries (concentration shift, 6.3-fold; p less than 0.05) but not in the saphenous veins. Endothelial removal augmented the response to the peptide (at 3 x 10(-7) M) in internal mammary arteries (p less than 0.05) but not in veins. In the artery, EDRF released by acetylcholine or bradykinin reversed endothelin-1-induced contractions; in saphenous veins, both agonists were much less effective compared with the artery and veins contracted with norepinephrine (p less than 0.005-0.01). This inhibition of endothelium-dependent relaxations in veins occurred at half-maximal contractions but was most prominent at maximal contractions to the peptide. Nitric oxide similarly inhibited contractions to endothelin-1 and norepinephrine in internal mammary arteries, whereas in veins that were contracted with endothelin-1 but not with norepinephrine, the relaxations were blunted (p less than 0.005). The nitric oxide donor SIN-1 and sodium nitroprusside induced complete relaxations of internal mammary arteries but were less effective in veins contracted with endothelin-1 (p less than 0.005). Thus, in normal human arteries, EDRF inhibits endothelin-1-induced contractions, whereas the peptide specifically attenuates the effects of EDRF and nitrovasodilators in veins. This may be important in pathological conditions associated with increased levels of endothelin-1 and in veins used as coronary bypass grafts.

Acetylcholine

[Diagnostic value of CK-MB for the determination of perioperative infarct in coronary artery bypass operation].

To assess the diagnostic value of CK-MB determinations after CABG surgery to detect or exclude perioperative myocardial infarction, 228 consecutive patients were studied with serial ECGs, as well as pre- and postoperative left heart catheterization and thallium-201-scintigraphy. CK-MB values above or below 100 U/l had a sensitivity and specificity of 73% each. There was a linear correlation between CK-MB values and total ischemic time. Thus, an increasing amount of myocardium is lost with each additional minute of ischemia despite today's methods of myocardial protection. Due to its low diagnostic accuracy CK-MB seems not to be very helpful for the diagnosis of perioperative myocardial infarction.

Adult