Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it i... more Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it is important to establish the superior immunosuppressive agent for the individual patient. In the present study, 121 patients, 61 randomly assigned to FK506- and 60 assigned to CsA-based immunosuppression, were analyzed according to the primary diagnosis for liver transplantation. One-year patient survival was similar in all groups. However, the incidence and severity of acute rejection within the 1st year after transplantation was significantly higher in patients transplanted due to HCV disease who were receiving FK506 (58.8%) compared with those patients receiving CsA (27.8%; p < or = 0.05). Furthermore, the incidence of moderate and severe neurotoxicity was significantly higher during the 1st month after LTX in patients transplanted owing to HCV disease treated with FK506 (35.3%) compared with those patients receiving CsA (16.7%; p < or = 0.05). Irrespective of the immunosuppress...
In a 58-year-old woman with erythropoietic protoporphyria, asymptomatic liver involvement had bee... more In a 58-year-old woman with erythropoietic protoporphyria, asymptomatic liver involvement had been diagnosed 12 years earlier. For more than 20 years the patient had been known to have symptomatic gallstones. A mild polyneuropathy of the lower limbs had been diagnosed several years ago. In December 1992, she presented with colicky upper abdominal pain, dyspepsia and mild jaundice. Diagnosis of beginning cholestasis in erythrohepatic protoporphyria and coincidental choledocholithiasis was made. A causal relation between choledocholithiasis and deterioration of liver function was assumed. Endoscopic extraction of the bile duct stones, however, could not prevent the development of terminal hepatic failure. Biochemically, an excessive protoporphyrinemia and coproporphyrinuria were found. Five weeks after presentation, the patient underwent orthotopic liver transplantation. Immediately after the operation she developed a severe axonal neuropathy with cranial nerve involvement. One year a...
Regional cerebral blood flow (rCBF) was evaluated quantitatively by 99mTc hexamethyl propyleneami... more Regional cerebral blood flow (rCBF) was evaluated quantitatively by 99mTc hexamethyl propyleneamine oxime and single photon emission CT (SPECT) during the interictal phase in 52 patients with focal epilepsy. The results were compared with those obtained by electroencephalography (EEG), CT, and magnetic resonance (MR) imaging. Twenty-four of the 52 patients had one area of local hypoperfusion whereas 7 patients showed an area of local hyperperfusion. In 20 of the 52 patients, both reduced and elevated rCBF values were found. One patient had a normal perfusion pattern. The SPECT findings correlated well with the foci shown by EEG, both with regard to the sides affected and the locations of the regions of altered perfusion. The MR images showed focal lesions in only approximately one-half of the patients examined, and CT in even fewer.
Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neuro... more Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neurotoxicity may be evoked by various perioperative factors or develop due to drug-specific toxicity of immunosuppression. We evaluated the incidence of neurotoxicity in 121 patients, 61 randomly assigned to FK506 and 60 to CsA-based immunosuppression. The incidence of moderate or severe neurotoxicity was markedly higher in patients treated with FK506 in the early postoperative period (21.3% vs. 11.7% in patients receiving CsA), after retransplantation (100% vs. 0% in patients receiving CsA), and late (8 of 10 patients; P &lt; or = 0.05 vs. CsA). Furthermore late neurotoxicity was highly associated with severe infections and MOFS, which had a lethal outcome in more than 50% of the patients. Patients who subsequently died developed neurologic symptoms in 67% of the cases. These patients also experienced moderate or severe neurotoxicity significantly more often in the early postoperative period compared with patients with a successful outcome (50% vs. 17.3%; P &lt; or = 0.01). However, various blood and serum parameters, including ALT, bilirubin, urea, creatinine and glucose, when analyzed alone or in multivariate fashion, also correlated significantly with the incidence and severity of early postoperative neurotoxicity, indicating that neurotoxicity following LTX may be caused by various factors and is not exclusively a drug-specific side effect of immunosuppression.
Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neuro... more Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neurotoxicity may be evoked by various perioperative factors or develop due to drug-specific toxicity of immunosuppression. We evaluated the incidence of neurotoxicity in 121 patients, 61 randomly assigned to FK506 and 60 to CsA-based immunosuppression. The incidence of moderate or severe neurotoxicity was markedly higher in patients treated with FK506 in the early postoperative period (21.3% vs. 11.7% in patients receiving CsA), after retransplantation (100% vs. 0% in patients receiving CsA), and late (8 of 10 patients; P &lt; or = 0.05 vs. CsA). Furthermore late neurotoxicity was highly associated with severe infections and MOFS, which had a lethal outcome in more than 50% of the patients. Patients who subsequently died developed neurologic symptoms in 67% of the cases. These patients also experienced moderate or severe neurotoxicity significantly more often in the early postoperative period compared with patients with a successful outcome (50% vs. 17.3%; P &lt; or = 0.01). However, various blood and serum parameters, including ALT, bilirubin, urea, creatinine and glucose, when analyzed alone or in multivariate fashion, also correlated significantly with the incidence and severity of early postoperative neurotoxicity, indicating that neurotoxicity following LTX may be caused by various factors and is not exclusively a drug-specific side effect of immunosuppression.
Single photon emission computed tomography (SPECT) examinations of regional cerebral blood flow (... more Single photon emission computed tomography (SPECT) examinations of regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were carried out in 23 patients with 19 subacute and 7 chronic cerebral infarctions. Corresponding magnetic resonance (MR) examinations (unenhanced and contrast enhanced scans) were done within a time interval of 2 days. Although all subacute lesions showed an increased rCBV, the rCBF could be either increased or decreased. Contrast enhancement in MR was associated with increased rCBV but not with increased rCBF. In all chronic lesions rCBV and rCBF were decreased and there was no contrast enhancement detectable in MR. The application of Gd-diethylenetriamine pentaacetic acid as contrast agent in MR demonstrates blood-brain barrier disruption as focal or gyral contrast enhancement in cerebral infarction. The SPECT examinations revealed an increased rCBV indicating a vasodilation or vasoparalysis. The rCBF was either increased or decreased depending on the collateral formation or recanalization of occluded vessels.
Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients wi... more Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with ...
Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it i... more Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it is important to establish the superior immunosuppressive agent for the individual patient. In the present study, 121 patients, 61 randomly assigned to FK506- and 60 assigned to CsA-based immunosuppression, were analyzed according to the primary diagnosis for liver transplantation. One-year patient survival was similar in all groups. However, the incidence and severity of acute rejection within the 1st year after transplantation was significantly higher in patients transplanted due to HCV disease who were receiving FK506 (58.8%) compared with those patients receiving CsA (27.8%; p < or = 0.05). Furthermore, the incidence of moderate and severe neurotoxicity was significantly higher during the 1st month after LTX in patients transplanted owing to HCV disease treated with FK506 (35.3%) compared with those patients receiving CsA (16.7%; p < or = 0.05). Irrespective of the immunosuppress...
In a 58-year-old woman with erythropoietic protoporphyria, asymptomatic liver involvement had bee... more In a 58-year-old woman with erythropoietic protoporphyria, asymptomatic liver involvement had been diagnosed 12 years earlier. For more than 20 years the patient had been known to have symptomatic gallstones. A mild polyneuropathy of the lower limbs had been diagnosed several years ago. In December 1992, she presented with colicky upper abdominal pain, dyspepsia and mild jaundice. Diagnosis of beginning cholestasis in erythrohepatic protoporphyria and coincidental choledocholithiasis was made. A causal relation between choledocholithiasis and deterioration of liver function was assumed. Endoscopic extraction of the bile duct stones, however, could not prevent the development of terminal hepatic failure. Biochemically, an excessive protoporphyrinemia and coproporphyrinuria were found. Five weeks after presentation, the patient underwent orthotopic liver transplantation. Immediately after the operation she developed a severe axonal neuropathy with cranial nerve involvement. One year a...
Regional cerebral blood flow (rCBF) was evaluated quantitatively by 99mTc hexamethyl propyleneami... more Regional cerebral blood flow (rCBF) was evaluated quantitatively by 99mTc hexamethyl propyleneamine oxime and single photon emission CT (SPECT) during the interictal phase in 52 patients with focal epilepsy. The results were compared with those obtained by electroencephalography (EEG), CT, and magnetic resonance (MR) imaging. Twenty-four of the 52 patients had one area of local hypoperfusion whereas 7 patients showed an area of local hyperperfusion. In 20 of the 52 patients, both reduced and elevated rCBF values were found. One patient had a normal perfusion pattern. The SPECT findings correlated well with the foci shown by EEG, both with regard to the sides affected and the locations of the regions of altered perfusion. The MR images showed focal lesions in only approximately one-half of the patients examined, and CT in even fewer.
Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neuro... more Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neurotoxicity may be evoked by various perioperative factors or develop due to drug-specific toxicity of immunosuppression. We evaluated the incidence of neurotoxicity in 121 patients, 61 randomly assigned to FK506 and 60 to CsA-based immunosuppression. The incidence of moderate or severe neurotoxicity was markedly higher in patients treated with FK506 in the early postoperative period (21.3% vs. 11.7% in patients receiving CsA), after retransplantation (100% vs. 0% in patients receiving CsA), and late (8 of 10 patients; P &lt; or = 0.05 vs. CsA). Furthermore late neurotoxicity was highly associated with severe infections and MOFS, which had a lethal outcome in more than 50% of the patients. Patients who subsequently died developed neurologic symptoms in 67% of the cases. These patients also experienced moderate or severe neurotoxicity significantly more often in the early postoperative period compared with patients with a successful outcome (50% vs. 17.3%; P &lt; or = 0.01). However, various blood and serum parameters, including ALT, bilirubin, urea, creatinine and glucose, when analyzed alone or in multivariate fashion, also correlated significantly with the incidence and severity of early postoperative neurotoxicity, indicating that neurotoxicity following LTX may be caused by various factors and is not exclusively a drug-specific side effect of immunosuppression.
Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neuro... more Neurotoxicity represents a serious complication following orthotopic liver transplantation. Neurotoxicity may be evoked by various perioperative factors or develop due to drug-specific toxicity of immunosuppression. We evaluated the incidence of neurotoxicity in 121 patients, 61 randomly assigned to FK506 and 60 to CsA-based immunosuppression. The incidence of moderate or severe neurotoxicity was markedly higher in patients treated with FK506 in the early postoperative period (21.3% vs. 11.7% in patients receiving CsA), after retransplantation (100% vs. 0% in patients receiving CsA), and late (8 of 10 patients; P &lt; or = 0.05 vs. CsA). Furthermore late neurotoxicity was highly associated with severe infections and MOFS, which had a lethal outcome in more than 50% of the patients. Patients who subsequently died developed neurologic symptoms in 67% of the cases. These patients also experienced moderate or severe neurotoxicity significantly more often in the early postoperative period compared with patients with a successful outcome (50% vs. 17.3%; P &lt; or = 0.01). However, various blood and serum parameters, including ALT, bilirubin, urea, creatinine and glucose, when analyzed alone or in multivariate fashion, also correlated significantly with the incidence and severity of early postoperative neurotoxicity, indicating that neurotoxicity following LTX may be caused by various factors and is not exclusively a drug-specific side effect of immunosuppression.
Single photon emission computed tomography (SPECT) examinations of regional cerebral blood flow (... more Single photon emission computed tomography (SPECT) examinations of regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) were carried out in 23 patients with 19 subacute and 7 chronic cerebral infarctions. Corresponding magnetic resonance (MR) examinations (unenhanced and contrast enhanced scans) were done within a time interval of 2 days. Although all subacute lesions showed an increased rCBV, the rCBF could be either increased or decreased. Contrast enhancement in MR was associated with increased rCBV but not with increased rCBF. In all chronic lesions rCBV and rCBF were decreased and there was no contrast enhancement detectable in MR. The application of Gd-diethylenetriamine pentaacetic acid as contrast agent in MR demonstrates blood-brain barrier disruption as focal or gyral contrast enhancement in cerebral infarction. The SPECT examinations revealed an increased rCBV indicating a vasodilation or vasoparalysis. The rCBF was either increased or decreased depending on the collateral formation or recanalization of occluded vessels.
Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients wi... more Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with ...
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Papers by Walter Christe