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Biomedical subjects

A W Lohse

Publications and source records attributed to A W Lohse.

At least 19 recordsLinked to original sources

Multiplex neuritis in a patient with autoimmune hepatitis: a case report.

A 37-year old woman presented with a 9-year history of hepatitis of unknown origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune hepatitis (AIH) was diagnosed on the basis of elevated aminotransferases, soluble liver antigen/liver pancreas (SLA/LP) autoantibodies and characteristic histology. Immunosuppressive therapy led to rapid normalization of aminotransferases. Two years later, the patient developed left sided hemisensory deficits under maintenance therapy of prednisolone and azathioprine (AZT). Later she developed right foot drop and paraesthesia in the ulnar innervation territory on both sides. Magnetic resonance imaging (MRI) and cerebral panangiography suggested cerebral vasculitis. Neurological investigation and electromyography disclosed multiplex neuritis (MN) probably due to vasculitis. Consistent with this diagnosis, autoantibodies to extractable nuclear antigens were detectable in serum. Immunosuppression was changed to oral 150 mg cyclophosphamide (CPM0) per day. Prednisolone was increased to 40 mg/d and then gradually tapered to 5 mg. Oral CPM was administered up to a total dose of 40 g and then substituted by 6 times of an intervall infusion therapy of CPM (600 mg/m(2)). Almost complete motoric remission was achieved after 3 mo of CPM. Sensibility remained reduced in the right peroneal innervation territory. Follow-up of cranial MRI provided stable findings without any new or progressive lesions. This is the first report of multiplex neuritis in a patient with autoimmune hepatitis.

Adult↗

Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95- and TRAIL receptor-mediated apoptosis and chemotherapy.

Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy, leading to a poor prognosis of advanced disease. Inhibitors of histone deacetylase (HDACi) induce re-differentiation in tumor cells and thereby re-establish sensitivity towards apoptotic stimuli. HDACi are entering the clinical stage of tumor treatment, and several substances are currently being tested in clinical trials to prove their efficacy in the treatment of leukemias and solid tumors. In this study, we investigated the impact of the HDACi valproic acid (VA) on TRAIL- and CD95-mediated apoptosis in hepatoma cells, as well as its sensitizing effect on a chemotherapeutic agent. Treatment of HepG2 cells with VA increased sensitivity to CD95-mediated apoptosis (4% apoptosis vs. 42%), and treatment with epirubicin (74% vs. 90% viability). Caspase-3 activity was significantly enhanced in cells treated with VA plus anti-CD95 antibodies compared to cells treated with antibodies alone. In parallel, VA strongly augmented the effect of TNF-related apoptosis-inducing ligand (TRAIL or Apo2 ligand) on HepG2 cells (10% vs. 58% apoptosis). VA induced down-regulation of cellular FLICE-inhibitory protein (c-FLIP/CASH, also known as Casper/iFLICE/FLAME-1/CLARP/MRIT/usurpin), providing a possible molecular mechanism underlying the increased sensitivity towards cell death-mediated apoptosis. HDAC inhibitors are a promising class for the treatment of leukemias. In addition, among other class members, VA deserves further evaluation as a treatment option for patients with advanced HCC.

Antineoplastic Combined Chemotherapy Protocols↗

[Therapeutic options for nonalcoholic fatty liver disease and steatohepatitis].

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as one of the most common causes of chronic liver damage in the western world. It is strongly associated with insulin resistance, obesity and other features of the metabolic syndrome. The entity NAFLD embraces a clinical spectrum from benign steatosis over steatohepatitis to hepatic cirrhosis with its complications liver failure and hepatocellular carcinoma. Treatment is currently based on prescriptive diet and physical exercise. A well-defined pharmacotherapy of NAFLD still remains to be established due to the lack of randomized, controlled trials. Yet, for several drugs such as Metformin and Thiazolidinediones, smaller trials report promising results.

Diet Therapy↗

[Liver and rheumatism].

There are multiple relations between rheumatic diseases and the liver, nevertheless the liver is extremely rare involved in rheumatic diseases. "Elevated liver enzymes" are quite often found in patients who are under the medication with immunosuppressive drugs or/and non-steroidal antirheumatics. The most frequent cause for "elevated liver enzymes" are toxic and allergic side effects of drugs; however, in rare cases it might be extremely helpful to examine, whether an independent liver disease exists. Underlying liver diseases which might be associated with the rheumatic disorder or exist accidentally may change the therapeutic management of the patient. If the liver disease present can cause the rheumatic disorder (e. g. virus-induced vasculitis, hemochromatosis), a specific hepatological therapy should precede the immunosuppression.

Antirheumatic Agents↗

Prospective comparison of cardiopulmonary events during minilaparoscopy and colonoscopy under conscious sedation.

BACKGROUND AND STUDY AIMS: Cardiorespiratory parameters were examined throughout diagnostic minilaparoscopy procedures. The same parameters were analyzed during colonoscopy, and the data were compared. PATIENTS AND METHODS: Sixty-five consecutive unselected patients undergoing minilaparoscopy (group 1: ASA I, n = 34; group 2: ASA II/III, n = 31) and 61 consecutive unselected patients undergoing colonoscopy (group 3: ASA I, n = 31; group 4: ASA II/III, n = 30) were included. Oxygen saturation (Sao (2)), heart rate (HR) and mean arterial pressure (RRm) were measured continuously, and 12-lead electrocardiography (ECG) recordings were made at specific times during each procedure. RESULTS: Minor differences were observed, particularly after premedication, probably due to different dosage regimens and timing in the two examination techniques. After premedication, testing for differences from baseline values showed a minor decrease in Sao (2) and RRm in the minilaparoscopy groups in comparison with the colonoscopy groups (median Sao (2), group 1: 99.9 % +/- 0 vs. group 3 : 100 % -1, P = 0.0078; median RRm, group 1: 99.5 - 4 mm Hg vs. group 3 : 96 -16 mm Hg, P = 0.046, and median RRm, group 2 : 110 + 1 mm Hg vs. group 4 : 101 -13.5 mm Hg, P = 0.0007). HR increased in minilaparoscopy in comparison with colonoscopy (median HR: group 2 : 77 + 4 beats/min vs. group 4 : 75.5 +/- 0 beats/min; P = 0.01). Comparison of defined relevant pathological changes in Sao (2), RRm, HR, and ECG showed no significant differences. DISCUSSION: These data indicate that diagnostic minilaparoscopy under conscious sedation is only associated with limited risk in patients with compensated cardiopulmonary diseases. This is probably due to the low insufflation pressure used.

Blood Pressure↗

Minilaparoscopy in the diagnosis of peritoneal tumor spread: prospective controlled comparison with computed tomography.

BACKGROUND: Early diagnosis of peritoneal spread in malignant disease prevents unnecessary laparotomies. Minimally invasive laparoscopy with the patient under conscious sedation is a new, easily feasible diagnostic technique. This study compares prospective and controlled diagnostic minilaparoscopy with computed tomography (CT) scan for the diagnosis of peritoneal metastases. METHODS: In this study, 56 patients with malignant disease were prospectively investigated with diagnostic minilaparoscopy and CT scan. RESULTS: The study criteria were fulfilled by 54 patients. Minilaparoscopy detected peritoneal carcinosis in 28 of 54 cases, whereas CT detected the disease in 14 of 54 cases. For 36 patients, the diagnosis could be verified by histologic examination of peritoneal biopsies or laparotomy. In this group, minilaparoscopy detected peritoneal carcinosis in 25 of 36 cases, whereas CT detected the disease in 12 of 36 cases. CONCLUSIONS: Minilaparoscopy was more sensitive than CT in detecting peritoneal carcinosis (100% vs 47.8%; p < 0.01). Considering its low grade of invasiveness and superior sensitivity, minilaparoscopy should be regarded as the procedure of choice for the early detection of peritoneal carcinosis.

Adult↗

Preoperative imaging of hilar cholangiocarcinoma: surgical evaluation of standard practises.

UNLABELLED: It was the goal of this study to compare the results of the preoperative diagnostic workup (ERC, MRC, and PTC) with the tumor extent of the surgical specimen in patients with hilar cholangiocarcinoma (hilCC). PATIENTS AND METHODS: Between 9/97 and 12/2002 82 patients with hilCC were treated at our institution. In 59 patients tumor resection was feasible. Preoperative ERC, MRC and PTC - blinded for the idendity of the patients - were analysed retrospectively and compared with the surgical specimen. RESULTS: PTC resulted in significantly superior visualization of the bile ducts including the hilar lesion compared to ERC and MRC (p < 0.01). ERC, MRC and PTC were correct in predicting tumor extent in 29, 36 and 53 % of cases, respectively. The extent of the tumor was overestimated in 42 % (ERC), 41 % (MRC) and 31 % (PTC). Underestimation or wrong assessment or no decision at all occurred in 31, 23 and 16 %, respectively. In 20 patients results of all three diagnostic methods were available allowing a statistical comparison regarding the resection to be performed: PTC was superior to ERC (McNemar test:p < 0.01), but not to MRC. In the patients with overestimated tumor extent both the rate of curative resections and survival were similar to the other resected patients. DISCUSSION: In contrast to most reports in the literature, ERC and MRC were found to be of limited reliability regarding the assessment of tumor extent. PTC proved to be the most reliable approach. Overestimation of the tumor extent, which may lead to exclude the patient from potentially curative surgery, was the most common mistake in each diagnostic modality.

Bile Duct Neoplasms↗

[Autoimmune liver disease: diagnosis and therapy].

Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and overlap syndromes of these three disease entities are regarded as autoimmune liver diseases. These conditions are important differential diagnoses of elevated liver function tests as about 10 % of liver transplantations in Europe and North America are for these indications. The diagnosis is often difficult but can be facilitated by sequential measurement of relevant autoantibodies, exclusion of other liver disease, ultrasound, ERCP and liver histology. In AIH immunosuppressive therapy has been shown to prevent or stop the development of cirrhosis and improve the prognosis of the patients decisively. In other autoimmune liver diseases this evidence is missing making individual therapeutic decisions necessary. Ursodesoxycholic acid (UDCA) seems to slow disease progression in particular in early stages of PBC.

Adult↗

[Diagnostic imaging of hilar cholangiocarcinoma: preoperative evaluation of ERC, MRC and PTC in comparison with histopathology].

PURPOSE: To compare the results of the preoperative workup consisting of endoscopic retrograde cholangiography (ERC), magnetic resonance cholangiography (MRC), and percutaneous resonance cholangiography (PTC) with the tumor extent of the surgical specimen in patients with hilar cholangiocarcinoma (hilCC). MATERIALS AND METHODS: Between 9/1997 and 12/2002, 59 patients with hilCC tumor underwent surgical resection. Preoperative ERC, MRC, and PTC were analyzed, blinded for the identity of the patient, and compared with the surgical specimen. For this retrospective analysis, 55 of the initial 59 ERCs, 39 of the initial 40 MRCs and 32 of the initial 38 PTCs were available. Most of the ERCs and MRCs had been performed at referring institutions by various investigators. In 20 patients, all three imaging modalities were available for direct comparison. RESULTS: The mean scores of the visualization of the bile ducts and tumor differ considerably for ERC, MRC and PTC, with PTC visualizing the bile ducts better than ERC (p < 0.001) and MRC (p = 0.019). The tumor classification according to Bismuth and Corlette was correctly predicted by ERC in 29 %, by MRC in 36 % and by PTC in 53 %. The tumor extent was overestimated in 40 % (ERC), 41 % (MRC) and 31 % (PTC) and underestimated in less than 10 % for all modalities. Twenty patients, who underwent all three imaging modalities, were included in an additional analysis for a direct comparison of ERC, MRC and PTC. PTC provided correct or acceptable information on tumor extent in 19 of 20 patients, MRC in 15 of 20 patients, and ERC in only 11 of 20 patients. The statistical analysis revealed a significant superiority of PTC to ERC (McNemar test: p < 0.01) but not to MRC (p = 0.22). DISCUSSION: The management of patients with hilar cholangiocarcinoma requires a high degree of expertise in diagnostic imaging techniques. Cholangiography should not only define the location but also visualize the uppermost extent of the tumor to determine resectability. In contrast to most reports in the literature, ERC and MRC were found to be of limited reliability regarding the assessment of the tumor extent. ERC may be more and more reserved for patients considered for nonsurgical intervention or palliation. PTC proved to be the most reliable approach. MRC represents a noninvasive diagnostic tool for the evaluation of malignant perihilar biliary obstructions, but should be performed at highest quality using state-of-the-art MRI techniques. The most common mistake of each diagnostic modality was an overestimated tumor extent, which may exclude patients from potentially curative surgery.

Aged↗

[Arterial back table pressure perfusion prevents ischemic biliary lesions after orthotopic liver transplantation].

INTRODUCTION: Ischemic biliary lesions are a threatening complication following orthotopic liver transplantation. Their exact pathophysiological mechanism is unknown so far, but insufficient perfusion of biliary arterial vessels might be responsible for the development of these lesions. This might be changed by improved perfusion techniques. We performed a controlled study of cases since February 2000. MATERIALS AND METHODS: We used arterial back table pressure perfusion to achieve reliable perfusion of the capillary system of the biliary tract, which may be impaired by the high viscosity of University of Wisconsin solution. In this study, 190 orthotopic liver transplantations performed between September 1997 and July 2002 were investigated with regard to ischemic biliary lesions. RESULTS: One hundred thirty-one grafts were preserved by in situ standard perfusion including portal perfusion,whereas additional arterial back table pressure perfusion was performed in 59 cases. Donor-related factors, recipient age, indications for transplantation, transplantation techniques, and ischemia times were comparable between groups. Twenty-one (16%) of the patients in the standard perfusion group and only one of the those receiving arterial back table pressure perfusion developed ischemic biliary lesions. This difference was highly significant (P=0.004). Maximal aspartate aminotransferase and alanine aminotransferase levels in the first 3 days were significantly lower in the arterial back table pressure perfusion group (P>0.05). CONCLUSION: Arterial back table pressure perfusion is an easy and reliable method for preventing ischemic biliary lesions in orthotopic liver transplantation. It should, therefore, be the standard technique in liver procurement.

Adenosine↗

The role of monocyte chemoattractant protein-1 in orthotopic liver transplantation.

Hepatic ischemia reperfusion injury as well as acute graft rejection (RE) after orthotopic liver transplantation (OLT) are associated with leukocyte invasion of the graft. Local synthesis of chemokines is a key reaction in the recruitment and activation of inflammatory leukocytes and consequent liver damage. In this paper we describe the role of monocyte chemoattractant protein (MCP)-1 (CCL2) in human OLT. We investigated the serum CC-chemokine levels for MCP-1 by specific ELISAs after OLT in 105 human liver allografts between September 1997 and January 2001. One hour after reperfusion we saw a significant (t test) increase of MCP-1 in peripheral blood (92.5 +/- 85.8 pg/mL to 774.2 +/- 319.6 pg/mL, 8.3-fold, P <.0001), hepatic venous blood (92.5 +/- 85.8 pg/mL to 866.7 +/- 376.1 pg/mL, 9.3-fold, P <.0001), and portal venous blood (92.5 +/- 85.8 pg/mL to 792.9 +/- 408.0 pg/mL, 8.5-fold, P < 0.0001) during hepatic ischemia reperfusion injury. An analysis of the correlation (Spearman's test, rs) between the expression of MCP-1 and the AST (rs 0.555, P <.025) and ALT (rs 0.852, P <.0001) showed a significant linear correlation. During RE a significant (t test) increase of MCP-1 (125.5 +/- 95.6 pg/mL to 188.5 +/- 124.6 pg/mL, 3.86-fold, P <.0001) was demonstrated. The successful treatment of the RE led again to a decline to lower base levels. Hepatic ischemia reperfusion syndrome as well as RE after OLT are characterized by typical patterns of CCL-2 overexpression. This finding proposes a new noninvasive, early diagnostic test after OLT.

Acute Disease↗

Minilaparoscopy in the diagnosis of cirrhosis: superiority in patients with Child-Pugh A and macronodular disease.

BACKGROUND AND STUDY AIMS: The diagnosis of cirrhosis has prognostic and therapeutic implications, but early forms are difficult to diagnose. Laparoscopy with histology has been reported to be superior to histology alone, but is often considered to be too invasive. This study aimed to assess whether minilaparoscopy offers similarly high sensitivity coupled with only minor invasiveness. PATIENTS AND METHODS: Minilaparoscopy with biopsy was performed in 226 consecutive patients with chronic liver disease. Cirrhosis was diagnosed macroscopically primarily on the basis of nodularity in a nontumorous liver. A histological diagnosis using the modified Knodell score was made without knowledge of the macroscopic assessment. RESULTS: Biopsies from 22 patients were inadequate for histological assessment, and 16 of these were considered to be cirrhotic from macroscopic observation. Out of 204 liver biopsies, 94 (46 %) were macroscopically identified as cirrhotic; 68/204 (33 %) showed stage 5 or 6 fibrosis (incomplete or complete cirrhosis). Histological understaging occurred mainly in patients who were otherwise diagnosed as having early Child-Pugh A cirrhosis, macroscopically incomplete cirrhosis and macronodular cirrhosis; 4/204 (2 %) of patients with cirrhosis histologically were understaged macroscopically. CONCLUSIONS: Macroscopic evaluation during minilaparoscopy increases the sensitivity of detection of liver cirrhosis, compared with biopsy alone, by more than 30 %. Because of its minimal invasiveness, minilaparoscopy combined with biopsy is recommended as a superior method for the staging of chronic liver disease.

Adolescent↗

[Coping in patients after liver transplantation with regard to their membership in a self-group].

BACKGROUND: Within the past 15 years, liver transplantation has proven itself to be the treatment of choice among patients with terminal liver disease. The one-year survival rate is about 80 %; after 8 years 61 % of the patients are still alive. The present study investigates the influence of active or depressive coping on the physical and mental quality of life in two different groups of patients after liver transplantation. METHODS: Members (n = 65) and non-members (n = 20) of a German self-help group were asked to fill out a postal survey. Patients were included if their liver transplantation was conducted 6 to 36 months ago. The health-related quality of life was surveyed using the SF-36 and coping strategies were investigated with the Freiburg questionnaire on coping with illness. RESULTS: All patients had a good physical and mental quality of life compared with a German normative sample. Members of the self-help group showed substantially higher active coping with illness (p < 0.0001), but only depressive coping correlates (negatively) with physical as well as with mental health-related quality of life (r between -0.24 and -0.68). This was true for both groups investigated. CONCLUSION: Based on an overall good health-related quality of life, depressive coping as well as aspects of the social environment contribute considerably in determining the well-being and quality of life in patients after liver transplantation.

Adaptation, Psychological↗

Minilaparoscopy-guided spleen biopsy in systemic disease with splenomegaly of unknown origin.

With the advent of a minimally invasive laparoscopy technique, the advantages of diagnostic laparoscopy are being rediscovered. We report here on four patients with systemic disease of unknown origin and splenomegaly, in whom minilaparoscopy-guided splenic biopsy yielded a definitive diagnosis. Four patients with unclear systemic disease were studied using diagnostic minilaparoscopy and guided spleen biopsy, after failure of diagnostic work-up. Minilaparoscopic spleen biopsy revealed the diagnosis of a B-cell non-Hodgkin's lymphoma in two cases. In one patient, who had a history of Still's disease, the spleen biopsy showed granulocytic infiltration in the spleen typical of an acute episode of Still's disease. One patient with a known immunodeficiency syndrome (stage C III) showed multiple hypodense lesions in the spleen. Biopsy allowed a diagnosis of mycobacterial infection, with identification of Mycobacterium tuberculosis. No major complications occurred in any of the four cases; post-biopsy bleeding was observed in three of the four, but was easily managed by argon plasma coagulation or application of fibrin glue, or both. We recommend the use of spleen biopsy as a diagnostic tool in splenopathy of unknown origin if previous diagnostic methods have failed to yield a definitive diagnosis.

Acquired Immunodeficiency Syndrome↗

Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics.

BACKGROUND: Antibodies to soluble liver antigen/liver pancreas (SLA/LP) are specific markers of autoimmune hepatitis. Their target antigen has recently been cloned. AIMS: To establish standardised immunoassays using the recombinant antigen, and to assess the frequency and significance of seropositivity in patients from different countries. METHODS: An enzyme linked immunoassay was developed using purified recombinant antigen and validated by testing sera from 200 healthy blood donors and 1026 patients with various liver and non-liver diseases. The assay was then applied to 454 sera from 419 patients with autoimmune hepatitis from different countries. All sera were also tested by inhibition immunoassay and western blot. RESULTS: Antibodies were reliably detected by the recombinant immunoassay and occurred exclusively in patients with autoimmune liver disease. Twenty three of 149 patients from the USA (15%), 23/132 from Brazil (17%), 21/108 from Germany (19%), and 2/30 from Japan (7%) were seropositive. Clinical features at presentation were similar between seropositive and seronegative patients. However, relapse after corticosteroid withdrawal or during maintenance therapy occurred more commonly in seropositive patients. CONCLUSIONS: Antibodies to SLA/LP can be reliably detected by these standardised immunoassays based on recombinant antigen. Antibodies to SLA/LP occur with similar frequencies in different geographical regions, races, and age groups, and are of exquisite diagnostic specificity. Whether SLA/LP positive patients represent a clinically distinct subgroup remains to be determined; relapse during treatment reduction appeared to be more common in the SLA/LP group.

Adolescent↗