Search PubMed⌕ Search

Biomedical subjects

E Hiller

Publications and source records attributed to E Hiller.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Multi-organ involvement in recurrent Moschcowitz disease. Splenectomy as ultima ratio in a therapeutic dilemma?].

BACKGROUND: The symptoms primarily described in Morbus Moschcowitz included thrombocytopenic purpura and hemolytic anemia. In addition it presents with a variety of clinical manifestations depending on the organs involved (i.e. neurological, renal, gastrointestinal, cardiac involvement). It is a rare disease and the pathogenesis still remains unclear. The efficacy of derived therapeutical concepts can hardly be assessed in controlled trials. CONCLUSION: Currently the main option seems to be plasma therapy. In non-responders surgical procedures (splenectomy) may be of benefit to the patient.

Female↗
PubMed1998

Changes in platelet membrane glycoproteins before bone marrow transplantation and after engraftment--a pilot study.

Thrombotic complications are observed in patients undergoing bone marrow transplantation despite thrombocytopenia and impaired coagulation due to liver function disturbances. Endothelial cell damage which is involved in the pathogenesis of major transplant related complications like graft-versus-host disease, veno-occlusive disease, sepsis or microangiopathy may be a contributing factor. Little is known about platelet function in bone marrow transplant recipients. In order to study functional alterations in circulating platelets we investigated unstimulated and ADP-stimulated platelets of 10 bone marrow transplant recipients ex vivo by flow cytometry in a pilot study using a panel of monoclonal antibodies to characterize changes in membrane glycoproteins. Samples were collected before and during conditioning and at three timepoints after engraftment. 10 healthy volunteers served as controls. Platelets of bone marrow transplant recipients showed partly a significant, higher expression of surface bound fibrinogen, activated fibrinogen receptor, and glycoprotein Ib as compared to controls. P-selectin, a marker of platelet degranulation was significantly elevated after ADP-induced stimulation at all timepoints compared to controls. Only marginal differences were found for GP IIb/IIIa surface expression. The data point to an increased platelet activation state in bone marrow transplant recipients which might contribute to the thrombotic phenomena observed in these patients.

Adenosine Diphosphate↗
PubMed1998

Laparoscopic splenectomy for idiopathic thrombocytopenic purpura. A 1-year follow-up study.

BACKGROUND: Laparoscopic splenectomy is a novel approach for the treatment of idiopathic thrombocytopenic purpura (ITP) in patients requiring surgical intervention. This technique was used for treatment in 16 consecutive patients. Follow-up was initiated at a median of 13.5 months after surgery to determine whether or not laparoscopic splenectomy is a safe and successful procedure that should be used in all patients requiring splenectomy for ITP. METHODS: Sixteen patients underwent laparoscopic splenectomy for ITP between May 1994 and September 1996. They were evaluated prospectively prior to surgery, immediately following surgery, at discharge, and at 13.5 months following surgery (n = 14) to determine the short- and long-term results of the procedure. RESULTS: Mean operation time was 123.4 +/- 12.1 min, and there were no significant intra- or postoperative complications. Mean intraoperative blood loss was 437.5 +/- 73.5 ml. Autologous blood transfusion was necessary in one patient (6.3%). Mean organ weight was 202.2 +/- 47.3 g. Mean postoperative hospital stay was 4.6 +/- 0. 4 days. Before discharge, mean platelet count rose by 100.7%. At follow-up (13.5 months postoperatively), it was 77.7% above preoperative values. No additional surgery was necessary in any of the patients undergoing laparoscopic splenectomy, and hematologic success was achieved in 12 patients (85.7%). CONCLUSIONS: Our results clearly indicate that laparoscopic splenectomy is a safe and successful procedure in patients suffering from ITP. It offers the well-known advantages of minimal invasive surgery as well as the surgical effectiveness of the open approach. This surgical technique should therefore be considered in all patients requiring splenectomy for the treatment of ITP.

Adolescent↗
PubMed1997

Plasminogen activator inhibitor-1 confirms the diagnosis of hepatic veno-occlusive disease in patients with hyperbilirubinemia after bone marrow transplantation.

Hepatic veno-occlusive disease (VOD) is a frequent and severe complication after bone marrow transplantation (BMT). We previously have described plasminogen activator inhibitor-1 (PAI-1) as a possible marker of VOD. To confirm the significance of this finding, we now determined PAI-1 levels in 31 of 186 consecutive patients undergoing BMT who developed hyperbilirubinemia greater than 3 mg/dL for various reasons. Diagnoses were made by clinical criteria and confirmed by biopsy in 23 of 31 patients. They included VOD (n = 7), acute graft-versus-host disease (GVHD) of the liver (n = 7), and other hepatic injury (n = 17). PAI-1 (mean +/- SD) was significantly (P < .001) elevated in patients with VOD (321.6 +/- 161.2 ng/mL) as compared with patients with GVHD (22.8 +/- 8.4 ng/mL) or other hepatic damage (32.8 +/- 30.8 ng/mL) at the timepoint of bilirubin increase. At the peak bilirubin concentration, the corresponding PAI-1 levels were 426.1 +/- 230.0 ng/mL in patients with VOD, 41.0 +/- 20.6 ng/ mL in patients with GVHD, and 44.6 +/- 32.9 ng/mL in patients with other hepatic injury (P < .001 VOD v GVHD/other hepatic injury). Our results underline the relevance of PAI-1 in the differential diagnosis of hyperbilirubinemia after BMT and its significance as a sensitive and specific marker of severe VOD.

Adult↗
PubMed1997

Laboratory markers of veno-occlusive disease in the course of bone marrow and subsequent liver transplantation.

Plasminogen activator inhibitor 1 (PAI-1) and amino-propeptide of type III procollagen (PIIINP) have been described as markers of hepatic veno-occlusive disease (VOD) after bone marrow transplantation (BMT). We determined these parameters in two patients undergoing BMT and subsequent liver transplantation due to VOD. Previously normal PAI-1 levels (maximum 30.0 ng/ml in patient 1, 23.7 ng/ml in patient 2) were elevated for the first time in both patients at the time of clinically diagnosed VOD on days 40 and 20, respectively (patient 1: 317.5 ng/ml; patient 2: 317.2 ng/ml). Levels remained elevated until liver transplantation was performed on days 79 and 41, respectively. Baseline levels (day -8) of aminopropeptide of type III collagen (patient 1: 4.44 microg/l; patient 2: 8.1 microg/l) peaked at the time of BMT in both patients (155.0 microg/l and 108.3 microg/l). After an intermittent decrease at the time of discharge on day 32, a second elevation was observed in patient 1 when she was readmitted and presented with typical signs of VOD on day 40. In patient 2, PIIINP levels remained high until VOD was diagnosed (day 20) and liver transplantation was performed. After liver transplantation, PAI-1 levels normalized in both patients and PIIINP levels declined. Both patients died due to infectious complications and multiorgan failure on days 141 and 101, respectively. Whereas the early rise of PIIINP did not correlate with the clinical onset of VOD, the results emphasise the relevance of PAI-1 for diagnosing VOD.

Acute Disease↗
PubMed1997

Endothelial cell markers in bone marrow transplant recipients with and without acute graft-versus-host disease.

To investigate endothelial cell alterations in BMT recipients developing acute graft-versus-host disease (aGVHD) we determined levels of the endothelial cell markers von Willebrand factor (VWF) and thrombomodulin (TM) in 57 patients undergoing BMT. Before conditioning VWF and TM levels did not differ significantly between transplant recipients who later developed no or mild (grade I) aGVHD (group A, allogeneic n = 22, autologous n = 7; VWF 136.0 +/- 44.1%; TM 29.5 +/- 18.0 ng/ml), and those with moderate or severe (grade II or III) aGVHD (group B, n = 28; VWF 142.2 +/- 37.6%; TM 35.2 +/- 20.1 ng/ml). A first significant rise of both VWF and TM level was noted after conditioning (day 0) both in group A (VWF 197.0 +/- 113.3%; P < 0.001; TM 39.3 +/- 23.3 ng/ml; P < 0.01) as well as in group B (VWF 201.7 +/- 53.3%; P < 0.0001; TM 43.5 +/- 23.5 ng/ml; P < 0.05). Subgroup analysis of autografted patients revealed no significant increase after conditioning in these patients. At the time of engraftment and onset of aGVHD (day 21), when VWF and TM levels within the groups were significantly elevated as compared with baseline (day -8) levels, group B patients (62.7 +/- 38.5 ng/ml) had significantly higher (P < 0.01) TM levels than patients of group A (37.4 +/- 19.6 ng/ml). This significant elevation also persisted at the end of the investigational period (day 28; group B: 56.0 +/- 37.6 ng/ml; group A: 38.2 +/- 23.7 ng/ml; P < 0.01). An elevation of endothelial cell markers is found in the course of BMT, particularly after conditioning and at the time of engraftment. This increase is pronounced in patients with aGVHD suggesting not only epithelial cell but also endothelial cell injury during aGVHD.

Acute Disease↗
PubMed1997

Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin's disease.

PURPOSE: To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field (IF/BF) and noninvolved extended-field (EF/IF) sites in patients with intermediate-stage Hodgkin's disease (HD). MATERIALS AND METHODS: HD patients in stage I to IIIA with a large mediastinal mass, E stage, or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by EF irradiation in two successive trials (HD1 and HD5). In the HD1 trial (1983 to 1988), 146 patients who responded to chemotherapy were randomized to receive 20 Gy (70 patients) or 40 Gy (76 patients) of EF irradiation in all fields outside bulky disease sites. A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 (1988 to 1993) were treated with 30 Gy. Bulky disease always received 40 Gy. RESULTS: Freedom-from-treatment-failure (FFTF) and survival (SV) curves showed no differences between the 20-, 30-, and 40-Gy groups. However, acute toxicities were more frequent in the 40-Gy arm. Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites (n = 5) or had an extranodal relapse (n = 9) or both (n = 4). After 5 years, the cumulative risk for relapse in bulky sites is 10%, despite 40 Gy of radiation. CONCLUSION: Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD. Relapse patterns indicate that patients destined to relapse need more systemic, rather than local, treatment. Based on our data, we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy.

Adolescent↗
PubMed1996

Protein C, protein S and antithrombin III levels in the course of bone marrow and subsequent liver transplantation due to veno-occlusive disease.

Veno-occlusive disease (VOD) of the liver is one of the most frequent fatal complications after bone marrow transplantation (BMT). A decrease of natural anticoagulants, in particular protein C (PC), has been assumed to be involved in the pathogenesis of the disease. We determined PC and antithrombin III (AT III) levels in two patients undergoing BMT and subsequent liver transplantation due to VOD. Additionally, in one of the patients protein S (PS) levels were also measured. Normal baseline (day-8) PC levels (86 and 89%) were markedly reduced in both patients at the time of VOD manifestation on day 20 and 40, respectively (26 and 31%). PS levels lay within the normal range from day-8 (before myeloablative chemotherapy) until one week after clinical onset of VOD when substitution therapy with fresh frozen plasma (FFP) was initiated. AT III levels decreased moderately during the second and third posttransplant week, but were normal in the patient with a late clinical manifestation of VOD. In both patients PC and PS levels lay within the normal range after liver transplantation which was performed on day 41 and 79, respectively. AT III was substituted several times. Both patients died due to infectious complications on day 141 and 101, respectively. The data confirm previous reports that a decrease of PC is observed in BMT recipients and can be associated with hepatic vein occlusion. Whereas the relevance of AT III is uncertain, PS does not seem to be involved in the pathogenesis of VOD. Liver transplantation lead to normalization of PC levels, but its significance remains to be discussed in terms of ethical justifiability, medical feasibility and costs.

Acute Disease↗
PubMed1996

Hemostatic parameters in sepsis patients treated with anti-TNF alpha-monoclonal antibodies.

Tumor necrosis factor-alpha (TNF alpha) is a central mediator in the pathogenesis of sepsis. It also interferes with the hemostatic system and exerts and a net procoagulant effect. Since TNF alpha may contribute to thrombotic complications in sepsis patients, we determined markers of thrombin activation, parameters of the fibrinolytic system (D-dimer, tissue plasminogen activator antigen (tPA) urinary type plasminogen activator antigen (uPA), plasminogen activator inhibitor antigen (PAI-1) and von Willebrand factor antigen (vWF) in 30 patients with sepsis or septic shock. All patients were treated with standard therapy, but 14 patients were treated additionally with an anti-TNF alpha monoclonal antibody (MAK 195F); 16 patients served as historical controls. No significant effect of the antibody on the parameters of the hemostatic system could be determined. Our data speak against a modulation of coagulation or the fibrinolytic system by the monoclonal anti-TNF alpha antibody MAK 195F in this cohort of sepsis patients.

Adult↗
PubMed1995

Diagnostic accuracy of ultrasound and computed tomography in the staging of Hodgkin's disease. Verification by laparotomy in 100 cases.

BACKGROUND: A staging laparotomy still is considered the gold standard to detect occult abdominal involvement in Hodgkin's disease. Computed tomography and ultrasound are routinely available for diagnostic imaging. To the authors' knowledge, the exact contribution of ultrasound for the staging of Hodgkin's disease has not been reported in a large series of patients before this study. METHODS: The diagnostic accuracy of abdominal ultrasound was compared with that of computed tomography and laparotomy in 100 patients with biopsy-proven Hodgkin's disease. Liver, spleen, paraaortic, and iliac lymph nodes were evaluated separately. RESULTS: Seventeen patients had a higher disease stage after surgery (17%). Considering only patients without known abdominal disease (supradiaphragmatic involvement), 14/79 (18%) had a positive staging laparotomy. Ultrasound had superior sensitivity for detecting splenic involvement with Hodgkin's disease (sensitivity, 63% compared with 37% for computed tomography). The specificity of both methods for detecting splenic disease was identical (99% vs. 96%). Inhomogeneities of structure or small nodular infiltrates were detected preferentially by ultrasound. Hepatic involvement also was visualized better by ultrasound than by computed tomography. Lymph nodes at the splenic hilus were recognized by both methods with identical sensitivity (64% vs. 62%). Paraaortic and iliac lymph nodes were recognized with greater sensitivity by computed tomography than by ultrasound (sensitivity, 93% and 100% vs. 77% and 67%, respectively). CONCLUSIONS: These results indicate that ultrasound and computed tomography each have their weaknesses and strengths and therefore should be combined, if possible. Ultrasound is the fastest and least invasive method and has particular accuracy for detecting splenic involvement, whereas computed tomography is more accurate in detecting involvement of paraaortic or iliac lymph node. If cost is important in the staging of Hodgkin's disease and if computed tomography is considered the standard, patients whose results are negative by computed tomography should be examined by ultrasound, focusing on splenic texture and size. Even in the era of combined modality treatment, surgical staging may be necessary to detect occult abdominal disease in a certain number of cases.

Abdominal Neoplasms↗
PubMed1995

[Second malignancy in patients with Hodgkin disease in full remission. Interim results].

Among 345 patients with Hodgkin's disease (HD) in full remission and followed for a mean of 7.2 years (11 months-26 years) since the initial diagnosis, 33 were found to have a second malignancy. The cumulative incidence after 10 years was 13.5%, after 15 years 21%. Non-Hodgkin lymphoma was the most frequent (n = 7), followed by bronchial carcinoma (n = 5) and acute myeloid leukaemia (n = 3). There was a definitely increased risk in elder patients (P < 0.001) and in those who had had a splenectomy. There was no demonstrable effect of type of therapy, primary stage and frequency of recurrence. It is concluded that patients with Hodgkin's disease should have life-long oncological follow-up. This preliminary study is being extended into a multicentre investigation of a larger number of patients.

Adult↗
PubMed1995

Levels of the terminal complement complex, C3a-desArg and C1-inhibitor in adult patients with capillary leak syndrome following bone marrow transplantation.

Capillary leak syndrome (CLS) is a severe complication after bone marrow transplantation (BMT). To investigate whether there is a pathogenetic role of the complement system, we monitored the levels of the terminal complement complex C5b-9 (TCC) and C3a-desArg as indicators of an activation of the complement system and the inhibitor of the classical pathway of the complement cascade, C1 inhibitor (C1-INH), in 48 bone marrow transplant recipients from 1 week before to 5 weeks after transplantation. Capillary leak syndrome developed in 7 out of 48 patients between days 1 and 12 after BMT. Complement activation as indicated by TCC levels was more pronounced in patients with CLS (n = 7) from day -8 to +28 (p < 0.05; day -1) and the elevation of TCC levels lasted longer in CLS patients (peak day 21) than in patients without this complication (peak day 7). Mean C3a-desArg levels were highest in patients with CLS reaching a peak at day 7. During the early posttransplant period a significant elevation of C1-INH levels (p < 0.01 and p < 0.05 respectively) compared with baseline levels (day -8) was found in patients with and without CLS, which was more pronounced in those patients with CLS (p < 0.05). Although we could not observe an absolute C1-INH deficiency as compared to healthy individuals our data support the presence of a relative deficiency of the inhibitor which might explain the reported beneficial effects of C1-INH substitution in BMT related CLS.

Adult↗
PubMed1995

Bone marrow involvement in Hodgkin's disease: an analysis of 135 consecutive cases. German Hodgkin's Lymphoma Study Group.

PURPOSE: To describe the incidence of primary bone marrow involvement (BMI) in Hodgkin's disease (HD) and its correlation with clinical and laboratory features present at diagnosis, and to evaluate the prognostic relevance of BMI. PATIENTS AND METHODS: Between 1983 and 1991, 2,307 patients with HD were treated according to two trial generations (HD1-3 and HD4-6) of the German Hodgkin's Lymphoma Study Group (GHSG). RESULTS: One hundred thirty-five cases of primary BMI were observed. The incidence of BMI was 4.8% in the HD4-6 study generation, which included all stages. Among stage IV patients, 32% had BMI. Among those with BMI, other organs were also involved in 33%. Among all patients, the presence of BMI was significantly associated with B symptoms, lymph nodes on both sides of the diaphragm, mixed cellularity histologic subtype, leukocytopenia, anemia, thrombocytopenia, lactate dehydrogenase (LDH) level more than 400 U/L, and erythrocyte sedimentation rate (ESR) more than 40 mm/h. BMI was negatively correlated with a large mediastinal tumor (3.7% v 20.0% in non-BMI cases). Eighty-seven of 108 (81%) assessable patients with BMI achieved a complete remission (CR). This compares favorably with the overall CR rate in all stage IIIB/IV patients. Among stage IV patients, BMI has no prognostic relevance with regard to freedom from treatment failure and overall survival. Twenty-one patients with BMI relapsed after having achieved a CR. Only five of these (24%) again had a positive bone marrow biopsy. CONCLUSION: The prognosis of patients with BMI is not worse than the prognosis of other advanced-stage HD patients. BMI alone does not define a special high-risk group in which a different treatment approach is indicated.

Adult↗