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Biomedical subjects

S Hirt

Publications and source records attributed to S Hirt.

At least 19 recordsLinked to original sources
PubMed2006

[Mutation in factor II and factor V gene in patients with peripheral arterial occlusive disease].

Mutations in factor-V- and factor-II-genes are correlated with an increased risk for venous thrombosis according to the literature. The significance of the mutations in factor- II- and factor-V-genes for the development of the peripheral arterial occlusive disease is not known. Therefore, we investigated the presence of these mutations in 152 patients with documented peripheral arterial occlusive disease and 318 controls without peripheral arterial occlusive disease with polymerase chain reaction (PCR). There was no association between factor-II-mutation and peripheral arterial occlusive disease. The factor-V-mutation, however, was increased in patients with peripheral arterial occlusive disease double fold (12 positive cases in 318 controls, 12 positive cases in 152 patients with peripheral arterial occlusive disease). The significance level was reached (p = 0.05) in statistical analysis but the result did not fall below the significance level as necessary to reach statistical significance (odds ratio 2.19). Nevertheless, from these data we have to discuss a biological relevance of factor-V-mutation in the pathogenesis of peripheral arterial occlusive disease.

Arterial Occlusive Diseases↗
PubMed2005

Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX). In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n = 145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group). The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP-9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN. This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.

Adult↗
PubMed2003

[Extravertebral cement drainage with occlusion of the extradural venous plexus into the vena cava after vertebrobplasty. Case report and review of the literature].

This paper presents the case report of an 88 year old female who came to hospital suffering from a severe lower back pain. Ten days before, she had undergone a vertebroplasty with injection of cement into lumbar vertebra 3 because of an osteoporotic fracture. This treatment did not result in a reduction of the lower back pain, which was the main reason for the procedure. However, the patient claimed to have increasing pain radiating to her left leg. Furthermore, she suffered from numbness of her left leg. Clinical examination showed a lack of power in this leg according to hip flexion with a degree of 3/5. X-ray examinations showed paravertebral cement particles and led to the suspicion that the paravertebral cement had caused nerve root compression. MRI and CT myelography showed that the cement had drained into the intraspinal, extradural venous plexus (Batson's plexus). The plexus was filled out with cement between L2 and L5 on both sides. There was nearly no cement in the fractured vertebra L3, but cement had also run onto the paravertebral veins up to the vena cava, which was also involved. The cemented veins had led to a stenosis of the neuroforamina L2 and L3 on the left side. The result was compression of left L3 nerve root. After consulting with our vascular surgeons, we decided on a non-operative treatment. We prescribed a lumbar brace as external stabilisation and as an antithrombotic treatment we gave the patient weight adapted low molecular weight heparin.

Aged↗
PubMed2000

Computed chest tomography in an animal model for decompression sickness: radiologic, physiologic, and pathologic findings.

This study was conducted to investigate the early pulmonary effects of acute decompression in an animal model for human decompression sickness by CT and light microscopy. Ten test pigs were exposed to severe decompression stress in a chamber dive. Three pigs were kept at ambient pressure to serve as controls. Decompression stress was monitored by measurement of pulmonary artery pressure and arterial and venous Doppler recording of bubbles of inert gas. Chest CT was performed pre- and postdive and in addition the inflated lungs were examined after resection. Each lung was investigated by light microscopy. Hemodynamic data and bubble recordings reflected severe decompression stress in the ten test pigs. Computed tomography revealed large quantities of ectopic gas, predominantly intravascular, in three of ten pigs. These findings corresponded to maximum bubble counts in the Doppler study. The remaining test pigs showed lower bubble grades and no ectopic gas by CT. Sporadic interstitial edema was demonstrated in all animals--both test and control pigs--by CT of resected lungs and on histologic examination. A severe compression-decompression schedule can liberate large volumes of inert gas which are detectable by CT. Despite this severe decompression stress, which led to venous microembolism, CT and light microscopy did not demonstrate changes in lung structure related to the experimental dive. Increased extravascular lung water found in all animals may be due to infusion therapy.

Acute Disease↗
PubMed1999

Eosinophilic alveolitis in BAL after lung transplantation.

Lung transplantation has become a therapeutic option for patients with end stage lung disease. However, outcome after transplantation is complicated by episodes of rejection and infections. Bronchoalveolar lavage is a valuable tool in monitoring patients after transplantation, since it allows the detection of pathogens. A marker specifically indicating rejection from changes in BAL fluid has not been found yet. Especially changes in differential cell count, like lymphocytosis or an increase in polymorphnuclear granulocytes, are unspecific. The role of high eosinophil levels in BAL has not been elucidated yet. We analyzed 25 BAL samples and clinical data of 4 patients who underwent lung transplantation and presented with recurrent episodes of eosinophilic alveolitis in BAL. All patients demonstrated a deterioration of clinical condition, lung function, and blood gas analysis during times of eosinophilia in BAL, compared to previous examinations. In all cases, eosinophilia in BAL was accompanied by rejection. All patients were finally treated with high doses of steroids, resulting in improvement of all parameters. Eosinophilia was not associated with significant changes in the IL-5 concentration in BAL or the pattern of IL-5 expression in BAL cells. In conclusion, eosinophilic alveolitis may indicate acute rejection in patients after lung transplantation, if other causes of eosinophilia are excluded.

Bronchoalveolar Lavage Fluid↗
PubMed1999

Dantrolene sodium improves the force-frequency relationship and beta-adregenic responsiveness in failing human myocardium.

BACKGROUND: Failing human myocardium is characterized by a negative force-frequency relationship and impaired beta-adrenergic responsiveness which have been related to alterations of the intracellular Ca2+ homeostasis. Dantrolene sodium is a clinically used drug that modulates myocardial [Ca2+]i handling in animal models. This study investigated the effects of dantrolene sodium on intracellular Ca2+ handling and contractile function in failing human myocardium. METHODS AND RESULTS: Twenty-three muscle strips from human left ventricular trabeculae were obtained from patients undergoing heart transplantation for end-stage heart failure caused by idiopathic dilated cardiomyopathy (n = 15). Isometric contraction and intracellular Ca2+ transients (Ca2+ indicator: aequorin) were recorded simultaneously. The experiments were performed in three separate groups exposed to control condition (n = 8), addition of dantrolene (10 micromol/l; n = 8), or addition of verapamil (1 micromol/l; n = 7). Isoproterenol induced a moderate positive inotropic effect in the control group with a maximal increase of developed tension from 10.8 +/- 2.9 to 23.4 +/- 4.7 mN/mm2 and a parallel rise in peak systolic [Ca2+]i to a maximum of 1.36 +/- 0.20 micromol/l. Dantrolene significantly improved (10.2 +/- 3.8 to 32.4 +/- 0.9 mN/mm2) and verapamil blunted (8.3 +/- 2.8 to 17.1 +/- 4.3 mN/mm2) the inotropic response to isoproterenol. The diastolic and systolic [Ca2+]i during isoproterenol stimulation were slightly lower in the dantrolene group but significantly depressed in the verapamil group as compared to the control group. Similarly, analyses of force-frequency relationships revealed an improvement of developed tension in dantrolene-treated as compared to control preparations whereas the peak systolic [Ca2+]i was almost identical. CONCLUSION: Dantrolene improves the negative force-frequency relationship and beta-adrenergic responsiveness in failing human myocardium. These effects are not accompanied by an additional increase in intracellular [Ca2+]i but might be related to modifications of the diastolic [Ca2+]i homeostasis.

Adrenergic beta-Agonists↗
PubMed1999

Adhesion molecules in patients after lung transplantation.

Leukocyte adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and its ligands, are involved in inflammatory processes of the lung. For ICAM-1, differential expression during different kinds of complications after transplantation has been proposed. We analyzed the role of ICAM-1, CD18, CD11a, CD11b, and CD11c during episodes of rejection or infection in patients after lung transplantation and compared the results to episodes without apparent complication. A total of 98 bronchoalveolar lavage (BAL) samples and 90 serum samples were analyzed. ICAM-1, CD18, CD11a, CD11b, and CD11c expressions were detected immunocytochemically on alveolar macrophages. Soluble ICAM-1 was quantified in serum and BAL. In the control group, 49.8 +/- 18% of macrophages stained positive for CD11b. During rejection, the mean of cells showing CD11b on the surface was significantly higher (64.6 +/-11.4%) with no difference compared to episodes of infection (59.7 +/-22.7). All other epitopes were not expressed differently with regard to a normal clinical course or episodes of infection and rejections. In summary, assessment of ICAM-1 and corresponding ligands did not allow for a reliable discrimination between episodes of rejection or infection in lung transplantation.

Adolescent↗
PubMed1999

Dissociation of the effects of forskolin and dibutyryl cAMP on force of contraction and phospholamban phosphorylation in human heart failure.

Forskolin and dibutyryl cyclic adenosine monophosphate (cAMP) stimulate force of contraction independent of beta-adrenoceptor stimulation. We studied their effects on force of contraction and phosphorylation of regulatory proteins in isolated electrically driven trabeculae carneae from failing human ventricles. The phosphorylation state of the regulatory protein phospholamban was studied because its phosphorylation usually faithfully follows contractility. For comparison, the phosphorylation state of the inhibitory subunit of troponin was studied. The phosphorylation state was inferred from in vitro phosphorylation of homogenates with cAMP-dependent protein kinase in the presence of radioactive gamma[32P]ATP Proteins were separated by electrophoresis, and radioactivity in the proteins of interest was quantified. The maximal positive inotropic effects occurred at 30 microM forskolin and were attenuated in comparison with the maximal effects to dibutyryl cAMP (1 mM). Both forskolin and dibutyryl cAMP enhanced phospholamban phosphorylation. However, phospholamban phosphorylation in intact trabeculae treated with 30 microM forskolin and 1 mM dibutyryl cAMP was comparable. It is suggested that phospholamban phosphorylation can be dissociated from inotropy at least in isolated trabeculae from failing human hearts.

Adolescent↗
PubMed1998

Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle.

BACKGROUND: The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. METHODS AND RESULTS: We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7% versus 26.4+/-5.3%, P=0.001) and open probability within active sweeps (7.36+/-1.51% versus 3.18+/-1.33%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure. CONCLUSIONS: Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Platelet-derived interleukin-1 induces cytokine production, but not proliferation of human vascular smooth muscle cells.

During vascular injury, such as observed in atherosclerosis, restenosis, vasculitides, transplantation, or sepsis, vascular smooth muscle cells (SMC) can be exposed to platelets or platelet products. Under these conditions proliferation or cytokine production of SMC stimulated by platelets or platelet products may contribute to regulation of vascular pathogenesis. Thus, we investigated interleukin-6 (IL-6) and IL-8 production as well as proliferation of SMC in response to platelets or platelet lysates. Platelets not already preactivated by thrombin induced IL-6 (10- to 50-fold) or IL-8 production of unstimulated SMC in a cell number dependent fashion. Preactivation of platelets with thrombin potently increased the platelet-mediated IL-6 (50- to 1,000-fold) and IL-8 production of SMC. Hirudin specifically inhibited the activation of platelets with thrombin. Isolated platelets cultured in the absence of SMC did not contain detectable IL-6 or IL-8. Prestimulation (4 hours) of SMC with pathophysiologically relevant substances (lipopolysaccharide [LPS], tumor necrosis factor-alpha [TNF-alpha], or IL-1alpha) further increased the platelet-induced cytokine production. The platelet-derived SMC stimulatory activity was IL-1, since IL-1 receptor antagonist (IL-1-Ra) inhibited the platelet-induced cytokine production of SMC. Anti-platelet-derived growth factor (PDGF)-antibody did not further reduce this activity. Thrombin itself stimulated expression of IL-6 and IL-8 to some degree and induced IL-6 production of SMC synergistically with IL-1. Platelets also induced proliferation of SMC, however, anti-PDGF antibodies, rather than IL-1-Ra blocked this response. These data show that platelet-derived IL-1 stimulates cytokine production of vascular smooth muscle cells, indicating that platelet-derived IL-1 may contribute to regulation of local pathogenesis in the vessel wall by activation of the cytokine regulatory network.

Antibodies, Monoclonal↗
PubMed1998

Preserved Frank-Starling mechanism in human end stage heart failure.

OBJECTIVE: The goal of the present study was to examine the ability of failing myocardium to respond to enhanced preload with an increase in force development. METHODS: The effect of various preload conditions (2.5-15 mN) on force development was studied in right ventricular trabeculae carneae from explanted human failing hearts with ischemic cardiomyopathy (ICM, n = 5, 42 preparations) or idiopathic dilated cardiomyopathy (DCM, n = 9, 77 preparations). To determine the severity of cardiac impairment we measured the positive inotropic effect of beta-adrenoceptor stimulation and calcium (ISO/Ca2+ ratio) and the expression of atrial natriuretic peptide (ANP) mRNA in all hearts. RESULTS: (1) Force of contraction increased with stepwise augmentation of preload (length at 2.5 mN preload to length of maximal force development) from 3.7 +/- 0.5 (ICM) and 2.7 +/- 0.4 (DCM) to 8.3 +/- 0.9 and 6.5 +/- 0.8 mN/mm2, respectively (p < 0.05). (2) The ISO/Ca2+ ratio was 0.40 +/- 0.04 (ICM) and 0.35 +/- 0.03 (DCM), respectively. (3) ANP mRNA was expressed in all preparations, albeit at greatly varying levels (ICM 22.5 +/- 6.1 and DCM 18.7 +/- 4.7 normalized arbitrary units). (4) Contraction experiments performed in left ventricular tissue (n = 3, 32 preparations) essentially confirmed the results. CONCLUSION: The Frank-Starling mechanism is preserved in terminally failing human hearts irrespective of the underlying etiology. We found no relation between the severity of cardiac impairment as assessed by either ANP expression or the ISO/Ca2+ ratio and the ability of failing human myocardium to respond to enhanced preload with an increase in force development.

Adrenergic beta-Agonists↗
PubMed1998

Single-channel properties of L-type calcium channels from failing human ventricle.

OBJECTIVE: The aim of our study was to analyse the single-channel properties of L-type calcium channels from failing human heart and to compare them to the respective animal data. Furthermore, we intended to evaluate the feasibility of future single-channel studies on the role of calcium channels in the pathophysiology of heart failure. METHODS: Single L-type calcium channels were recorded in ventricular myocytes from explanted failing human heart, using the cell-attached configuration of the patch-clamp technique. RESULTS: One or more successful registrations of calcium channels could be obtained in 11 of 19 cell isolations. Determination of single-channel conductance yielded a mean value of 16.6 +/- 1.2 pS (70 mM Ba2+ as the charge carrier) under control conditions and 23.7 +/- 2.8 pS in presence of the calcium-channel agonist FPL 64176. The rapid gating process could be described by a C<-->C<-->O gating scheme. Slow gating analysis revealed a highly significant clustering of active and non-active sweeps. CONCLUSION: Single-channel measurements of L-type calcium channels in human failing ventricle are feasible and reproducible despite the varying patient characteristics. Their channel properties are qualitatively comparable to those found in other mammals. Whether there are quantitative differences due to the underlying heart failure can be elucidated in further studies.

Adult↗
PubMed1997

Detection of diastolic dysfunction: acoustic quantification (AQ) in comparison to Doppler echocardiography.

OBJECTIVES: To evaluate the potential of acoustic quantification (AQ) in detection of diastolic dysfunction in comparison to Doppler analysis, we investigated, as a model of restrictive filling pattern, nonrejecting heart transplant recipients early postoperatively. BACKGROUND: AQ, an ultrasonic backscatter imaging system, enables instantaneous calculation of cavity areas and thus provides a new approach to diastolic function. METHODS: Of 27 pts who have undergone heart transplantation, echocardiography has been performed at the day of biopsy. During a time course of 8 weeks echocardiographic data have been analysed at 3 different time points (early, mid and late) in 16 nonrejecting pts. Indexes of the area-change waveform and its 1. derivative (dA/dt) obtained by AQ were opposed to usual Doppler indexes. RESULTS: In comparing data of the early and late time point of investigation, significant changes of early diastolic filling were detectable by AQ as well as by Doppler: End-diastolic areas have increased (p < 0.001), while peak filling rate (p < 0.0001), slope of area change during rapid filling (p < 0.001) and amount of relative area change during rapid filling (p < 0.001) have decreased. Complementary, Doppler derived pressure half-time (p < 0.0001) and isovolumic relaxation time (p < 0.0001) have increased while the peak early filling velocity (p < 0.0001) and its time velocity integral (p < 0.001) have decreased. CONCLUSION: An initial restrictive filling pattern has improved 8 weeks postoperatively. Since multiple indexes, obtained from the area change waveforms, in particular the for end-diastolic area normalized peak filling rate, seem to be highly sensitive in detecting changes of diastolic function, AQ may play an important complementary role in non-invasive evaluation of restrictive filling pattern.

Adult↗
PubMed1996

Positive inotropic effects of the calcium sensitizer CGP 48506 in failing human myocardium.

In trabeculae carneae from failing human myocardium, CGP 48506 increased the force of contraction, which reached 310 +/- 41% of predrug values at 100 mumol/l. Its stereoisomer CGP 48508 did not affect the force of contraction (100 mumol/l). The positive inotropic effect of CGP 48506 was not sensitive to 10 mumol/l carbachol. The positive inotropic effect of CGP 48506 was accompanied by increases in time to peak tension and time of relaxation amounting to 175 +/- 4% and 205 +/- 15% of control, respectively, at 100 mumol/l. CGP 48506 but not CGP 48508 sensitized skinned trabeculae from failing human myocardium to calcium with an EC50 value of 10 mumol/l. However, CGP 48506 and CGP 48508 (up to 300 mumol/l) did not affect the activity of PDE isoenzymes I to IV from failing human myocardium. CGP 48506 is the first inotropic agent with calcium-sensitizing properties in the human heart that has been found to be devoid of inhibitory activity on human cardiac PDE isoenzymes.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Prevention of graft infection by bonding of gentamycin to Dacron prostheses.

To increase the efficacy of perioperative antibiotic prophylaxis in vascular surgery an experimental study including topical application of the gentamicin derivative EMD 46/217 and fibrin sealant as antibiotic carrier to Dacron prostheses was initiated. In vitro treatment of Dacron with gentamicin and fibrin was followed by constant antibiotic release for 3 weeks. In a subsequent animal study Dacron grafts were implanted in the aorta of 10 pigs after direct contamination with Staphylococcus aureus solution. One graft was pretreated with the antibiotic/fibrin compound, a second with the antibiotic alone. Grafts 3 (no pretreatment) and 4 (fibrin alone) served as controls. After 1 week the grafts and their corresponding implantation sites were excised for measurement of antibiotic content and for culture. The antibiotic content of grafts with the antibiotic/fibrin compound was 25.0 +/- 7.2 micrograms/gm wet weight, whereas Dacron pretreated with the antibiotic alone contained no measurable drug amounts except for one specimen (0.5 microgram/gm) (antibiotic/fibrin vs antibiotic, p less than .0005). The corresponding implantation sites to antibiotic/fibrin grafts contained 1.07 +/- 0.54 microgram/gm antibiotic, whereas in only 2/10 implantation sites of antibiotic grafts low antibiotic levels were found (0.05 and 0.2 microgram/gm) (antibiotic/fibrin vs antibiotic, p less than 0.005). All control grafts and 9/10 antibiotic grafts were infected. By contrast, only five were contaminated, and 5 of 10 remained sterile after culture (antibiotic/fibrin vs antibiotic, p less than 0.05). This finding correlates with the antibiotic content in the Dacron. It is concluded that pretreatment of prosthetic Dacron grafts with the antibiotic/fibrin compound results in binding of sufficient amounts of antibiotic for at least 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Increased messenger RNA level of the inhibitory G protein alpha subunit Gi alpha-2 in human end-stage heart failure.

In human heart failure the positive inotropic and cAMP-elevating effects of both beta-adrenoceptor agonists and phosphodiesterase inhibitors are diminished. This has been explained at least in part by an increase in the inhibitory signal-transducing G protein (Gi) and unchanged stimulatory G protein (Gs). In the present study we determined the mRNA expression pattern of the alpha subunits of Gi-1, Gi-2, Gi-3, and Gs in myocardial tissue samples of patients undergoing heart transplantation. Northern blot analysis of total RNA extracted from left ventricles with 32P-labeled cDNAs demonstrated expression of Gi alpha-2, Gi alpha-3, and Gs alpha mRNA. In contrast, Gi alpha-1 mRNA was not detectable. To investigate whether the increased ratio of Gi/Gs might be due to altered gene expression, we compared mRNA levels of Gi alpha-2, Gi alpha-3, and Gs alpha in left ventricular myocardium from failing hearts with idiopathic dilated cardiomyopathy (n = 8) and ischemic cardiomyopathy (n = 6) and from nonfailing hearts from transplant donors (n = 8). Compared with nonfailing control hearts, the Gi alpha-2 mRNA was increased by 75 +/- 26% (p less than 0.05) in idiopathic dilated cardiomyopathy hearts and 90 +/- 26% (p less than 0.05) in ischemic cardiomyopathy hearts. Gi alpha-3 and Gs alpha mRNA levels were similar in the three groups. The results suggest that as in other mammalian species, Gi alpha-2 and Gi alpha-3 mRNA are the predominant Gi alpha mRNA subtypes in human ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗