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Biomedical subjects

D Zenker

Publications and source records attributed to D Zenker.

16 recordsLinked to original sources
PubMed2003

Renal function and safety of heart transplant recipients switched to mycophenolate mofetil and low-dose cyclosporine.

BACKGROUND: We evaluated cyclosporine (CSA) dose reduction and mycophenolate mofetil (MMF) treatment versus maintained CSA dosage and azathioprine (AZA) in HTX regarding renal function and safety from CSA nephrotoxicity (creatinine > 1.7 mg/dL). METHODS: Fourteen recipients (group 1: 12 men, 2 women) with CSA-based immunosuppression (plus azathioprine and/or steroids) were started on 2000 mg MMF/d. Azathioprine was discontinued and CSA tapered to trough whole blood levels of 70 to 120 microg/L. Ten recipients (group 2: seven men, three women) were maintained on their CSA dosages. Creatinine clearance, serum creatinine, uric acid, urea nitrogen, and rejection were monitored. RESULTS: Mean age was 58 (range 44 to 69 years) and 48 years (range 24 to 61 years) in groups 1 and 2, respectively. In group 1 creatinine fell from 2.7 +/- 0.8 to 1.9 +/- 0.5 mg/dL (baseline vs control 2: P =.001); uric acid and urea nitrogen remained constant. CSA levels decreased from 173 +/- 56 to 110 +/- 33 microg/L (P =.02). In group 2 creatinine (2.4 +/- 0.7 vs 2.3 +/- 0.5 mg/dL), uric acid, urea nitrogen, and CSA levels remained constant. Comparison between groups showed higher creatinine clearance (50 +/- 18 vs 29 +/- 14 mL/min; group 1 vs group 2: P =.02), lower CSA levels (110 +/- 33 vs 161 +/- 35 microg/L; P <.001) and a trend toward lower serum creatinine (1.9 +/- 0.5 vs 2.3 +/- 0.5 mg/dL, P =.077). There were two rejections >/= 1B according to ISHLT in the study and four in the control group. Two deaths occurred in each group. CONCLUSIONS: Conversion from AZA to MMF after CSA reduction improves creatinine clearance in HTX recipients and reduces serum creatinine. No negative effect on patient safety was identified by rejection rate or survival.

Adult↗
PubMed2000

Polysorbate-80 coating enhances uptake of polybutylcyanoacrylate (PBCA)-nanoparticles by human and bovine primary brain capillary endothelial cells.

Certain drugs such as dalargin, loperamide or tubocurarine are not transported across the blood-brain barrier (BBB) and therefore exhibit no effects on the central nervous system. However, effects on the central nervous system can be observed when these drugs are loaded onto polybutylcyanoacrylate (PBCA)-nanoparticles and coated with polysorbate 80. The mechanism by which these complexed nanoparticles cross the BBB and exhibit their effects has not been elucidated. Cultured microvessel brain endothelial cells of human and bovine origin were used as an in vitro model for the BBB to gain further insight into the mechanism of uptake of nanoparticles. With cells from these species we were able to show that polysorbate 80-coated nanoparticles were taken up by brain endothelial cells much more rapidly and in significantly higher amounts (20-fold) than uncoated nanoparticles. The process of uptake was followed by fluorescence and confocal laser scanning microscopy. The results demonstrate that the nanoparticles are taken up by cells and that this uptake occurs via an endocytotic mechanism.

Animals↗
PubMed2000

Doppler-sonographic evidence of cerebral microembolism originating from a biventricular assist device.

The use of extracorporeal assist devices in heart failure is associated with the risk of thromboembolic complications [1]. Prove of thromboembolic material in the ventricles and tubes of the assist devices is difficult, and the clinical relevance of thrombotic material in the tubes is not clear. Here, we report on a patient with severe heart failure caused by endstage dilated cardiomyopathy who was bridged to transplantation using a biventricular assist device (BVAD). Five weeks after implantation, transcranial Doppler sonography (TCD) revealed high intensity transient signals (HITS) in basal cerebral arteries, suggesting continued cerebral microembolism. Apart from a correlation of these Doppler sonographic findings with neurological symptoms, macroscopic evidence of fibrin thrombi in the artificial ventricle, and post mortem confirmation of cerebral infarction could be proved.

Adult↗
PubMed1999

Hypercoagulability in a patient with hypodysfibrinogenemia: implications for clinical management.

Dysfibrinogenemia accounts for approximately 0.7% of thrombophilia in patients with venous thromboembolic disease. In 20% of these patients, plasma thrombophilic dysfibrinogen is below 1.0 mg/ml, defining hypodysfibrinogenemia. We describe a young female patient, in whom hypodysfibrinogenemia was the cause of several severe thromboembolic events which occurred even under oral anticoagulation monitored by a standard prothrombin time (PT) test. In this patient, the standard PT test according to Quick underestimated the plasma coagulability in vivo, presumably due to the low levels of dysfunctional fibrinogen as the substrate of the thromboplastin reagent. A PT test supplemented with bovine plasma fibrinogen (Thrombotest) revealed lower fibrinogen-independent international normalized ratio (INR) values in the proposita on oral anticoagulation compared to a control group with eufibrinogenemia. Monitoring therapy with the fibrinogen-independent Thrombotest secured safe anticoagulation in this patient. We suggest to consider PT tests with exogenous fibrinogen (e.g. Thrombotest) to monitor oral anticoagulation in the rare thrombophilic patients with hypodysfibrinogenemia.

Adult↗
PubMed1999

Coronary artery bypass procedures in septuagenarians are justified. Short and long-term results.

BACKGROUND: Elective coronary artery bypass surgery can be performed with low operative mortality. There is a controversial discussion whether short-term and long-term results of CABG justify this procedure in elderly patients. METHODS: To add to this discussion, we evaluated retrospectively, the clinical profile, operative technique, short- and long-term results of 1127 patients over 70 years of age who underwent myocardial revascularization between January 1985 and December 1996. RESULTS: Mean age of the cohort was 73.9 years and it rose continuously. In 1996, septuagenarians represented 21.5% of our coronary patients, in comparison to 6.4% in 1985. Analysis of risk factors showed an increasing prevalence of renal failure, obesity, hyperuricemia and a history of smoking. Preoperatively, 87% of our patients were in NYHA-class III or IV, and thus operated to relieve severe symptoms. The percentage of emergent operations decreased over the observed period by 10.3%. The internal mammary artery was used with rising frequency (44.8% in 1985-1992 vs 61.5% in 1993-1996). The number of simultaneous valve replacements increased, too. Postoperatively, we noted a rising incidence of respiratory failure (17.1%) and neurological disorders (13.7%). On the other hand, the need for intra-aortic balloon pumping and hemofiltration declined by 6.6% and 2.9%, respectively. Perioperative mortality (< or =24 hrs) was 3.65%, hospital mortality (< or =30 days) was 9.64%. The actuarial survival (standard error) at 1 year was 82% (+/-4.3%), and 65.7% (+/-3.8%) at 5 years. CONCLUSIONS: Our data suggest that coronary artery bypass grafting can be performed in septuagenarians at an acceptable risk. Since the large majority of patients improve symptomatically, surgery is a recommendable option for a growing number of elderly patients suffering from severe angina.

Aged↗
PubMed1998

Inhibition of endothelial receptor expression and of T-cell ligand activity by mycophenolate mofetil.

The novel immunosuppressive drug mycophenolate mofetil (CellCept, MMF) blocks DNA-synthesis by the inhibition of the enzyme inosine monophosphate dehydrogenase (IMDH). IMDH is also involved in the synthesis of adhesion receptors which are known to play an important role in the regulation of cell-cell contacts. Therefore, application of MMF might lead to a reduction of cellular infiltrates in the course of transplant rejection. To evaluate the therapeutic value of MMF, we investigated to what extent MMF blocks T-lymphocyte infiltration in vitro with regard to (a) adhesion to endothelial cells, (b) horizontal migration along these cells and (c) penetration through the endothelial cells. The results demonstrated a strong inhibition of both CD4+ and CD8+ T-cell adhesion and penetration by MMF. The ID50 value for CD4+ T-cell adhesion was calculated to be 0.03 microM and the ID50 value for CD4+ T-cell penetration 1.21 microM. MMF did not significantly influence the horizontal migration of T-lymphocytes along the human vascular endothelial cell (HUVEC) borders. FACS-analysis revealed a diminished E-selectin and P-selectin expression on endothelial cell membranes in the presence of MMF. Although MMF did not interfere with the synthesis of T-cell adhesion ligands, the binding activity of lymphocytic leucocyte function associated antigen 1 (LFA-1), very late antigen 4 (VLA-4) and PSGL-1 (P-selectin glycoprotein ligand 1) to immobilized intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin was impaired. Moreover, MMF prevented VLA-4 and PSGL-1 receptor accumulation on the membranes of T-cell pseudopodia. It can be concluded that MMF possesses potent infiltration blocking properties. MMF evoked down-regulation of specific endothelial membrane molecules and the loss of protein localization in the lymphocyte protrusions might be predominantly responsible for the observed blockade of cell adhesion and penetration.

CD4-Positive T-Lymphocytes↗
PubMed1998

Resection for CMV ileitis in a patient supported by a left-ventricular assist device.

We describe a patient requiring a HeartMate 1000 IP left-ventricular assist device (LVAD) due to cardiogenic shock. After prolonged gastrointestinal bleeding without identifying the source of bleeding technetium scintigraphy pointed to the right lower abdomen. The patient underwent a laparotomy and inflamed ileum was resected. Pathologic examination revealed cytomegalovirus ileitis. This was treated with ganciclovir and acyclovir. The patient is now (14 months later) awaiting heart transplantation since she could not be weaned from LVAD. The diagnostic and management problems are discussed as well as the relevance for future transplantation.

Adult↗
PubMed1998

Anterior ischemic optic neuropathy: a complication after extracorporal circulation.

INTRODUCTION: Anterior ischemic optic neuropathy (AION) describes a defect of the optic nerve leading to irreversible loss of vision in most cases. Pathophysiology of this disease is manifold and has been discussed as a posthemorrhagic complication as well as a neurological complication after operations with cardiopulmonary bypass. METHODS: On the basis of two cases, the clinical picture is described in relation to the available literature. Preoperative risk factors, operative data, cardiopulmonary-bypass, postoperative complications and clinical symptoms are discussed together with ophthalmologic findings in order to elucidate the pathophysiology of this process. RESULTS: There is no reliable and effective treatment of anterior ischemic optic neuropathy. Neither corticosteroids, osmotic diuretics, hemodilution nor surgical decompression of the optic nerve have proved successful. Hence, measures to avoid ischemic optic neuropathy have priority. The following risk factors were determined: History of glaucoma or other ophthalmological problems, prolonged cardiopulmonary bypass-time and myocardial ischemia, general oedema during cardiopulmonary bypass, excessive hemodilution with low hemoglobin and hematocrit, hypo- or hypertension, systemic hypothermia, need for vasoactive medication. CONCLUSIONS: Influenced by a variety of factors, pathophysiological microvascular changes provoke anterior ischemic neuropathy with sudden painless loss of vision, irreversible in most cases. Since therapeutic trials have failed, prevention of possible causes is the only way to avoid this rare but severe complication of cardiac surgery.

Adrenal Cortex Hormones↗
PubMed1997

Vascular complications related to intraaortic balloon counterpulsation: an analysis of ten years experience.

We have performed a retrospective review of our experience with the intraaortic balloon counterpulsation pump (IABP) during the last decade, to identify aspects of risk factors, complications, and management that affect peripheral vascular morbidity and mortality. Data from 472 patients who had the IABP inserted during the ten-year period from December 1985 to December 1995 were retrospectively reviewed. Risk factors, implantation techniques, complications, and significant variables were evaluated. One hundred forty-five vascular complications needed surgical therapy in 116 patients. Mean age was 62.2 +/- 12.9 years. There were 84 (72.5%) men and 32 (27.5%) women. Mortality rate was 28.3% (n = 181). The mortality for patients with ischemic vascular complications was significantly higher than in patients who did not suffer any vascular complication (59.6% vs 30.1%, p = 0.0001). Complications included acute limb arterial occlusion in 99 cases (68.3%), compartment syndrome in 27 (18.6%), groin hematoma in 15 (10.3%), and persistent lymph fistula in 4 (2.8%). Of these, 97 (76.9%) occurred during IABP therapy and 29 (23.1%) after IABP explantation. Thromboembolectomy was required for 61 (42.2%) of the ischemic limbs. Associated procedures were 24 (16.5%) profundaplasties, 10 (7%) infrainguinal bypasses (5 (3.4%) femoropopliteal supragenicular, 3 (2.2%) femoropopliteal infragenicular, and 2 (1.4%) infrapopliteal), 26 (17.9%) fasciotomies, and 5 (3.4%) amputations. A history of peripheral vascular disease (31 patients [43.6%] with vs 95 [23.6%] without, p < 0.05) and the presence of diabetes mellitus (70 patients [49.2%] with vs 56 [16.9%] without) increased the risk of limb ischemia significantly. Female sex, insertion of IABP by percutaneous technique, and direct removal with groin compression were associated with higher ischemic complication rates, the differences however were not significant. Itis concluded that 1. Limb ischemia remains the primary complication after IABP insertion; 2. Femoral artery thromboembolectomy is usually sufficient for revascularisation; 3. Adequate implantation and surgical explantation techniques are essential to reduce the IABP-related morbidity; 4. Identification of subclinical disease may aid in the management of subsequent acute limb ischemia; 5. The presence of peripheral vascular disease and diabetes mellitus are associated with higher ischemic complication rates.

Aged↗
PubMed1997

Urodilatin (INN:ularitide) as a new drug for the therapy of acute renal failure following cardiac surgery.

1. Acute renal failure is a severe complication following major cardiac surgery. 2. The effects of urodilatin were evaluated in a randomized, double-blind trial in patients suffering from incipient acute renal failure following cardiac surgery. 3. In the urodilatin group (n = 7) acute renal failure was reverted, whereas in the placebo group (n = 7) six patients had to be haemofiltered or haemodialysed (P < 0.005). 4. Urodilatin induced a rapid onset of diuresis in contrast to placebo-treated patients, who remained oliguric. 5. In the placebo group four of seven patients died while still on haemodialysis (mortality rate 57.1%) during a postoperative follow-up period of 60 days, while all patients treated with urodilatin survived. 6. On the basis of these results it would appear that urodilatin is an effective drug for the treatment of incipient oliguric acute renal failure following cardiac surgery and for avoiding haemodialysis/haemofiltration.

Acute Kidney Injury↗
PubMed1996

Acute renal failure following cardiac surgery is reverted by administration of Urodilatin (INN: Ularitide).

Acute renal failure (ARF) is a serious complication following cardiac surgery. This first controlled study was undertaken to verify, if Urodilatin (URO) infusion can revert incipient oliguric ARF after cardiac surgery. We conducted a randomized, double blind trial comparing 7 URO (20 ng/kg/min) with 7 placebo patients. Inclusion criterion was oliguria/anuria (< 0.5 ml/kg/hour) refractory to conventional treatment including administration of dopamine and furosemide. No patient in the URO treated group, but 6 patients in the placebo group had to be hemofiltered or hemodialyzed (p < 0.005) during the 7 day treatment period. In the URO group all 7 patients demonstrated a rapid recovery of diuresis after 2 - 8 hours of treatment that persisted throughout the treatment period. In contrast, placebo treated patients remained oliguric. Serum creatinine (SC) decreased in URO treated patients. No adverse effects were observed during URO administration. After termination of URO, 2 patients underwent hemodialysis for elevated blood urea nitrogen (BUN) values. In the postoperative follow-up period of 60 days, 4 out of 7 placebo treated patients died while still on hemodialysis. In contrast, all URO patients survived. URO is an effective drug to reverse oliguric ARF following cardiac surgery. Prolonged renal failure and renal replacement therapy can be avoided.

Acute Kidney Injury↗
PubMed1996

[Intraoperative acute aortic obstructive embolism].

UNLABELLED: We report a case of acute embolic obstruction of the aorta in a 36-year-old patient undergoing coronary artery bypass surgery. After declamping of the aorta at the end of extracorporeal circulation, blood pressure measured in the femoral artery dropped to 10-20 mmHg. Neither clinical signs of arterial hypotension nor a dysfunction of the arterial line could be observed. Cannulation of the left radial artery revealed a normal systemic blood pressure. After the end of surgery, pale and pulseless lower extremities were observed, suggesting arterial obstruction. A 6 X 3 cm embolus occluding the aortic bifurcation could be extracted with a Fogarty catheter; its origin was presumably an aneurysmatic area of the left ventricle. Surgical manipulation had mobilised the mural thrombus, which caused Leriche's syndrome after aortic declamping and defibrillation of the heart. CONCLUSION: In case of sudden alterations of lower extremity perfusion, anaesthetists and surgeons should consider the rare complication of acute embolic obstruction of the aorta originating from intracardiac thrombotic material. Routine monitoring with transoesophageal echocardiography should thus be considered in patients at risk for intracardiac thrombus formation.

Acute Disease↗
PubMed1992

[Vigilance disorders in intensive care patients. The central anticholinergic syndrome as a differential diagnosis of a brain stem lesion].

Four days after implantation of a biventricular assist device (Berlin heart) the 39-year-old patient showed a sudden loss of vigilance and tetraplegia. Clinical skills and neurophysiological states indicated a serious lesion of the brain stem. After a test application of Physostigmine 2 days later, the neurological deficits improved dramatically. The case demonstrates that neurological deficits can also be caused by or combined with an acute anticholinergic syndrome. The application of Physostigmine allows disorders caused by brain lesions to be differentiated from transitory syndromes.

Adult↗
PubMed1984

Guaran effect on rat intestinal absorption. A perfusion study.

Among the components of dietary fiber, the soluble polysaccharides, primarily guaran and pectin, have been found to impair intestinal absorption. Little is known, however, about the mechanism of this effect. The direct action of guaran on small intestinal absorption was evaluated by a single-pass perfusion technique. Guaran in the perfusate (1-7 g/L) inhibited small intestinal absorption of actively transported compounds, such as alpha-methyl-D-glucoside, cycloleucine, and taurocholate, and also of the passively permeating solutes 2-deoxy-D-glucose and urea. Viscosity-related inhibition by guaran was found to depend on the rate of perfusion and was only detectable at perfusion rates below 0.4-0.5 ml/min. Higher perfusion rates abolished and even reversed the inhibitory effect. The observed alterations of absorption rates caused by guaran were completely reversible after switching to a guaran-free perfusate. The concentration-dependent absorption of D-glucose and alpha-methyl-D-glucoside at perfusion rates of 0.4 and 0.2 ml/min, respectively, revealed an increase in the transport constant and essentially unaltered maximal transport capacity in the presence of guaran. Additionally, net water absorption changed to secretion upon addition of guaran. When pectin and carrageenan were used in solutions of comparable viscosity, their effect was similar to that of guaran. The results suggest a general mechanism by which soluble, viscosity-enhancing polysaccharides influence the intestinal absorption of nutrients. The most likely explanation appears to be an increase in the unstirred layer resistance to diffusion. Under our experimental conditions, this occurred at low perfusion rates, but was increasingly counteracted by raising the rate of perfusion.

Animals↗