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Biomedical subjects

M Kirsch

Publications and source records attributed to M Kirsch.

At least 19 recordsLinked to original sources

B-type natriuretic peptide to assess haemodynamic status after cardiac surgery.

BACKGROUND: B-type natriuretic peptide (BNP) is the most powerful hormonal marker of left ventricular dysfunction and could be considered as an indicator of ventricular preload. The aim of this prospective study was to compare the respective value of BNP and cardiac filling pressures to assess the response to volume load after cardiac surgery. METHODS: Thirty-seven mechanically ventilated patients suffering from acute circulatory failure immediately after cardiac surgery, and equipped with a pulmonary-artery catheter were included. All haemodynamic measurements were taken before and after volume expansion using 500 ml of 4% modified fluid gelatin. RESULTS: Fifteen patients were volume responders (CI increase>or=15%) and 22 were non-responders. Right atrial pressure, pulmonary-artery occlusion pressure and BNP before volume loading were not significantly different between the responders and non-responders. BNP concentration before volume infusion significantly correlated to preoperative left ventricular ejection fraction, aortic cross-clamping time, serum creatinine, mean pulmonary arterial pressure and intensive care unit duration whereas no correlation was found with pulmonary-artery occlusion pressure or cardiac index. CONCLUSION: BNP level after cardiac surgery was influenced by many perioperative variables, limiting its usefulness as an indicator of cardiac preload or a predictor of volume responsiveness in this population.

Aged↗

Endovascular management of dural carotid-cavernous sinus fistulas in 141 patients.

INTRODUCTION: The purpose of this study was to evaluate the single-centre experience with transvenous coil treatment of dural carotid-cavernous sinus fistulas. METHODS: Between November 1991 and December 2005, a total of 141 patients (112 female) with dural carotid-cavernous sinus fistula underwent 161 transvenous treatment sessions. The patient files and angiograms were analysed retrospectively. Clinical signs and symptoms included chemosis (94%), exophthalmos (87%), cranial nerve palsy (54%), increased intraocular pressure (60%), diplopia (51%), and impaired vision (28%). Angiography revealed in addition cortical drainage in 34% of the patients. Partial arterial embolization was carried out in 23% of the patients. Transvenous treatment comprised in by far the majority of patients complete filling of the cavernous sinus and the adjacent segment of the superior and inferior ophthalmic vein with detachable coils. RESULTS: Complete interruption of the arteriovenous shunt was achieved in 81% of the patients. A minor residual shunt (without cortical or ocular drainage) remained in 13%, a significant residual shunt (with cortical or ocular drainage) remained in 4%, and the attempted treatment failed in 2%. There was a tendency for ocular pressure-related symptoms to resolve rapidly, while cranial nerve palsy and diplopia improved slowly (65%) or did not change (11%). The 39 patients with visual impairment recovered within the first 2 weeks after endovascular treatment. After complete interruption of the arteriovenous shunt, no recurrence was observed. CONCLUSION: The transvenous coil occlusion of the superior and inferior ophthalmic veins and the cavernous sinus of the symptomatic eye is a highly efficient and safe treatment in dural carotid-cavernous sinus fistulas. In the majority of patients a significant and permanent improvement in clinical signs and symptoms can be achieved.

Adult↗

[Endovascular occlusion of the basilar artery for the treatment of dissecting and dysplastic fusiform aneurysms].

Dissecting aneurysms of the basilar artery trunk frequently affect young adults. Fusiform shape and narrowing of the proximal parent artery are typical features. Changes in aneurysm size and geometry may be observed more rapidly than in atherosclerotic or dysplastic aneurysms. Dissecting aneurysms carry a significant risk of rupture. Thrombotic or embolic occlusion of small pontine branches may cause ischemic symptoms. Sufficiently large aneurysms compress the adjacent brainstem. The operative treatment of these aneurysms is associated with unacceptable risks. At least one posterior communicating artery with normal calibre together with the ipsilateral P1 segment needs to provide adequate collateral flow to the upper basilar artery to allow endovascular coil occlusion of the segment that is affected by the dissection and/or fusiform aneurysmal dilatation. Four illustrative cases of endovascular coil occlusion of the basilar artery for the treatment of fusiform aneurysms are presented and discussed.

Adult↗

Endovascular treatment of small intracranial aneurysms: three alternatives to coil occlusion.

INTRODUCTION: Small intracranial aneurysms with a fundus diameter of 2 - 3 mm may rupture and are therefore potential targets for an endovascular approach in treatment. Currently available coil technology is less than optimal for the treatment of aneurysms within this size range. Even the smallest coils are sometimes too large. If such a minute coil can be introduced into a small aneurysm, the hemodynamic effect and the induced thrombosis are frequently inadequate to occlude the aneurysm sufficiently from the parent artery circulation. METHODS: Three technical alternatives for the endovascular treatment of small intracranial aneurysms not suitable for coil occlusion are illustrated with the following three case descriptions. RESULTS: Stent grafts are usable for the intracranial internal carotid artery and for the V4 segment. The stiffness of the stent and the high expansion pressures are the two major drawbacks. Coaxial deployment of two or more self-expanding porous stents can result in sufficient redirection of the blood flow to induce aneurysmal thrombosis. Deployment of multiple stents, however, may require several treatment sessions in order to allow for the integration of the stents into the vessel wall from session to session. A regular microcatheter can block aneurysmal inflow in aneurysms with a very narrow neck. This allows the occlusion of the aneurysm with an appropriate amount of highly concentrated, rapidly polymerizing glue. Polymer emboli may result from excessive or rapid glue injection. CONCLUSION: The available coil technology has inherent limitations in the treatment of very small intracranial aneurysms. Liquid embolic agents and stent-based extrasaccular treatment strategies may provide solutions for these challenging lesions.

Adult↗

Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice.

BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability of 5-HT is the 5-HT transporter (5-HTT) expressed by platelets and pulmonary vascular cells; 5-HTT is responsible for 5-HT uptake and subsequent inactivation of the amine passing through the lung. Here we investigated whether 5-HTT-deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy. METHODS AND RESULTS: Cardiac endothelial cells expressed large amounts of 5-HTT in wild-type mice. 5-HTT deficiency appeared to be associated with marked interstitial, perivascular, and valvular fibrosis as evidenced by staining of cardiac collagen in 5-HTT-KO mice. Histological analysis provided evidence for valvulopathy characterized by valvular hyperplasia and prominent fibrosis at the attachment site and base of the leaflets. Echocardiography revealed an increase in left ventricular lumen diameter and a decrease in left ventricular diameter fractional shortening. Although 5-HT1B receptors mediated the 5-HT-induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT1B receptors showed the same cardiac alterations as 5-HTT-KO mice. CONCLUSIONS: The present results establish a link between 5-HTT and the development of cardiac fibrosis and valvulopathy in vivo. 5-HTT-KO mice represent an especially relevant model for studying the mechanisms by which 5-HT induces valvulopathy.

Animals↗

[rFVIIa administration in patient with a left ventricular assistance patient].

We report the case of a left ventricular mechanical assistance (Incor Berlinheart) in a woman that experienced a postoperative non-surgical haemorrhagic complication following a reconstructive pedicled omentoplasty for implanted materials infection. After massive substitutive therapy failure at reducing blood loss and because of an hypovolaemic shock, high dosage (70 microg/kg twice) of recombinant activated factor VII (r-VIIa) was administrated resulting in spectacular cessation of bleeding and haemodynamic restoration. Continuous repeated clinical evaluation, cardiac echography and electronic monitoring of the axial pump device characteristic did not reveal any thromboembolic accident. This observation brings some indirect arguments for safe rFVIIa treatment in this type of pathology with a high thromboembolic risk.

Aged↗

Preoperative devascularization of a circumferential osteogenic metastasis to the upper cervical spine by direct percutaneous needle puncture: a technical note.

Direct percutaneous needle puncture (DPNP) for presurgical devascularization of head and neck as well as skull base tumours is an established, yet not widespread method. We present a case of a large and highly vascularized metastasis with partial destruction of the first two cervical vertebrae and encasement of the spinal cord that was successfully treated by DPNP for preoperative devascularization after an attempted endovascular embolization had failed. The lesion was safely and effectively devascularized, which facilitated the surgical removal. The case presented illustrates the technique and furthermore demonstrates its value.

Aged↗

Reconstructive treatment of dural arteriovenous fistulas of the transverse and sigmoid sinus: transvenous angioplasty and stent deployment.

Various techniques for the endovascular treatment of dural arteriovenous fistulas (dAVFs) of the transverse and sigmoid sinus have recently evolved. Transvenous coil occlusion of the involved segment and transarterial embolization of the feeding arteries with liquid agents are the commonest treatments utilized. However, with respect to venous hypertension as the probable pathogenic cause of this disorder, a nonocclusive or remodeling technique might be preferable. We will present a series involving four patients, treated with transvenous angioplasty and stent deployment as a definitive treatment of dAVFs of the transverse and sigmoid sinus. This method was used as a primary treatment or as an adjunct to previous noncurative transarterial n-butyl cyanoacrylate and particle embolization. In three of the four cases, complete occlusion of the fistula was achieved with confirmation of occlusion seen on follow-up angiographical studies. In one case a negligible and nonsymptomatic remnant of the fistula fed by the tentorial artery was left untreated. From our experience, we conclude that transvenous stent deployment is an alternative to traditional concepts. Additionally, the pathological theory of dAVFs in this region located in venous pouches of the sinus wall is supported by the fact that they can be occluded by mechanical compression during angioplasty and subsequently maintained by a stent.

Adult↗

Parameters affecting the display of antibodies on phage.

Despite the fact that a multitude of antibody phage display libraries has been built, systematic comparisons of critical design parameters are rare. Here we analysed the impact of various factors on the performance of the phage display system. First, we compared several vector designs for the display of Fab fragments of antibodies. Bicistronic as well as monocistronic expression of the antibody/pIII operon and vectors using fd-pIII as well as LC-pIII fusions were tested. Further, we evaluated the influence of glucose on the promoter induction. We compared monovalent versus oligovalent display of the antibody fragments and we used antibody fragments with different folding efficiency to assess the influence of the individual antibody sequences on the performance of the system. Finally, both phage display efficiency and yield of soluble Fab fragments were analysed. The significant differences found for phage yield, display of Fabs on the phage and expression of soluble Fabs suggest to use a bicistronic vector with an fd-fragment-pIII fusion for the construction of future Fab phage display libraries.

Animals↗

[Blood activation during long-term mechanical circulatory support].

Mechanical circulatory support has become an approved treatment option for patients with cardiogenic shock or end-stage heart failure. However, recipients of heart assist devices are prone to high incidences of bleeding, thrombo-embolic and infectious complications. The occurrence of these complications is favoured by systemic alterations of coagulation and fibrinolysis, inflammation and immune responses. Several studies have evaluated these pathophysiological changes in patients undergoing long term circulatory support with pulsatile devices. However, the systemic consequences of the more recently introduced rotary blood pumps remain largely unknown. The present review focuses on the systemic consequences of long term circulatory support with pulsatile and non-pulsatile devices.

Assisted Circulation↗

[No detectable nephrotoxic side effect using a dimer, non-ionic contrast media in cerebral perfusion computed tomography in case of suspected brain ischemia].

PURPOSE: In suspected brain ischemia, the perfusion cerebral computed tomography (cCT) should be performed with the lowest amount of contrast media to avoid a contrast media induced nephropathy (CIN) even if the patient already is in renal failure. We were interested to find the best parameters for this examination. MATERIAL AND METHODS: From February 2000 to March 2003, 138 patients (58 females, 80 males, mean age 66.8 years) underwent cCT-perfusion immediately after the admission to our stroke unit. Of these patients, 62% (n = 86) had normal renal function and 38% (n = 52) renal failure (up to 381 micromol/l basic serum creatinine). We varied volume (20-80 ml), flow (5 vs. 7.2 ml/s) and concentration (270 vs. 320 ml/mg iodine) of a dimer, non-ionic contrast media (Visipaque) to establish 5 groups. So we got patients receiving 6 g, 12 g, 16 g, 19 g and 25 g of iodine. After generating the perfusion maps, two radiologists reviewed the quality of the maps and scored it (1-5). We measured the serum creatinine before contrast application and at follow up cCT (days 3 and 7). RESULTS: The quality of the maps increases with increasing amount of iodine. However, the diagnostic result was not significantly better using more than about 16 g of iodine (e. g., 60 ml--7.2 ml/s--270 mg/ml) in cCT-perfusion studies. Only one patient had a pathologic increase in serum creatinine (day 1: 93; day 4: 146 micromol/l) but died at day 5 because of massive co-morbidity and septic pneumonia. No CIN occurred even in the patient group with pre-existent renal failure. CONCLUSIONS: About 60 ml contrast media and a moderate flow rate of about 7 ml/s ensure good results in perfusion-cCT, even if the patients have poor blood circulation or arteriosclerosis. The use of a dimer, non-ionic contrast media (range of 6-25 g iodine) seems to minimize the risk of CIN in the daily routine.

Aged↗

NAD(H) enhances the Cu(II)-mediated inactivation of lactate dehydrogenase by increasing the accessibility of sulfhydryl groups.

Copper ions are known to inactivate a variety of enzymes, and lactate dehydrogenase (LDH) is exceptionally sensitive to the presence of this metal. We now found that NADH strongly enhances the Cu(II)-mediated loss of LDH activity. Surprisingly, NADH was not oxidized in this process and also NAD+ promoted the Cu(II)-dependent inactivation of LDH. Catalase only partly protected the enzyme, whereas hypoxia even enhanced LDH inactivation. NAD(H) accelerated sulfhydryl (SH) group oxidation of LDH by 5,5-dithio-bis(2-nitrobenzoic acid) (DTNB), and, vice versa, LDH-mediated Cu(II) reduction. LDH activity was preserved by thiol donators and pyruvate and partially preserved by lactate and oxamate. Our results suggest that reactive oxygen species (ROS) are of minor importance for the inactivation of LDH induced by Cu(II)/NADH. We propose that conformational changes of the enzymes' active sites induced by NAD(H)-binding increase the accessibility of active sites' cysteine residues to Cu(II) thereby accelerating their oxidation and, consequently, loss of catalytic activity.

Animals↗

FISH studies on the telomeric regions of the T-cell acute lymphoblastic leukemia cell line CCRF-CEM.

So far, the problem of an influence of translocations on the telomeres of the involved chromosomes has not been addressed yet in human cells. Therefore, the telomeres of a karyotypically rather well characterized T-cell acute lymphoblastic leukemia (T-ALL) cell line (CCRF-CEM) with several marker chromosomes were examined using peptide nucleic acid (PNA) telomere FISH probes to compare the telomere length of these markers with that of the chromosome arms of their origin. In addition, chromosome libraries, centromeric probes, and subtelomeric DNA probes were used to further define the marker chromosomes. Two markers could be newly defined and a concise karyotype of the cell line could be obtained by these detailed examinations: 42-47,X,-X,del(5) (q35?),t(5;15)(q14;q13.2),t(8;9)(p11;p24),del(9)(:p13-->qter)/inv(9)(pter-->p12::q21-->p12::q21-->qter),+13,+20,+der(22)(p+ [HSR?])[cp]. The relative telomere length of all chromosomes showed considerable interchromosomal, intercellular, and inter-passage variation. However, it could be shown, that in four different passages of the examined cell line the observed differences between relative telomere lengths of the markers and the chromosomes of their origin, with two exceptions (short arms of del/inv9 and der22), were not significant. On the other hand, because of its mentioned variability, telomere length alone is not sufficient to reliably define the derivation of markers.

Cell Line, Tumor↗

Tumor necrosis factor alpha and glutathione interplay in chronic heart failure.

The pro-inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), in concert with neurohormones, contributes to chronic heart failure (CHF) progression. This implies that TNF a antagonism may constitute an important target for CHF therapy. However, clinical trials in CHF patients using compounds that trap TNF alpha, comprising infliximab, an antibody directed to TNF alpha, and etanercept, a soluble recombinant receptor of TNF alpha, gave disappointing results bringing back to light the dual, short-term beneficial and long-term harmful effect of TNF alpha. This review focuses on the dual, concentration- and time-related effects of TNF alpha, the yin and yang action of TNF alpha in cardiac ischemia/reperfusion and contraction. Importantly, the harmful effects of TNF a are related to glutathione deficiency, a common hallmark to several other chronic inflammatory diseases. Recently, in rat models of CHF, oral administration of the glutathione precursor, N-acetylcysteine (NAC), was shown to hinder pathways of TNF alpha harmful signalling and to rescue cardiac structure and function. These results suggest that glutathione deficiency in association with TNF alpha activation may play a role in the pathophysiology of CHF and that NAC may represent a potential therapy in CHF.

Acetylcysteine↗

Coil treatment of a fusiform upper basilar trunk aneurysm with a combination of "kissing" neuroform stents, TriSpan-, 3D- and fibered coils, and permanent implantation of the microguidewires.

Endovascular coil occlusion of fusiform intracranial aneurysms without sacrifice of the parent artery can be technically challenging. Bridging of wide aneurysm necks with stents is common practice for side-wall aneurysms but is less frequently used for bifurcation aneurysms. We describe the technical aspects of the successful coil occlusion of a fusiform aneurysm of the upper basilar trunk, with preservation of the parent vessel. The procedure comprised the following steps: (a) stenting of the left V1- and proximal V2 segments; (b) simultaneous deployment of two Neuroform stents from both P1 segments down to the basilar artery ("kissing" stents) (c) using a TriSpan device to hold (d) three-dimensional electrolytically detachable coils in place and (e) filling the aneurysmal lumen mainly with fibered electrolytically detachable coils; and finally (f) cutting the extracorporeal part of both microguidewires below the skin level in both groins, leaving the microguidewires as they were used for the deployment of the stents in place, thus reaching from both P2 segments down to the basilar artery and further proximally.

Basilar Artery↗

[Percutaneous thermoablation of lung metastases. Indication, performance, initial results, and imaging findings].

Not unlike thermoablation of liver metastases, thermoablation of metastases to the lungs is gaining clinical interest. Radiofrequency ablation and laser-induced interstitial thermotherapy are both used clinically. Initially it was suspected that percutaneous treatment of lung metastases would result in a rate of pneumothoraces and tissue reactions which would not be clinically acceptable. However, this did not prove true. Fear of pneumothoraces however did lead to the desire for an applicator with a maximally reduced diameter. While clinical results are not yet available, technical success rates of laser-induced interstitial thermotherapy of lung metastases are promising. The percentage of pneumothoraces does not differ significantly from that seen in diagnostic procedures. Large metastases may be treated by simultaneous use of multiple applicators or by repositioning of an applicator (pullback technique). Surgical experience is still guiding us in deciding which primaries' metastases may be successfully treated percutaneously. The literature indicates that lung metastases from colorectal primaries are especially suited. Radiotherapy is only an alternative method in cases of lung metastases if they cause symptoms (such as pain because of thorax infiltration or difficulty in breathing because of bronchial lesion). Due to the risk of radiation-induced pneumonia general radiotherapy is not to be recommended. The possibility of stereotactic ray treatment is being considered, but because breathing shifts the metastases it is not yet feasible. Therefore, percutaneous thermoablation could be used as a minimally invasive, rather riskless therapeutic option for a relatively high percentage of inoperable lung metastases.

Catheter Ablation↗