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Biomedical subjects

H Riess

Publications and source records attributed to H Riess.

At least 73 records · Page 4Linked to original sources
PubMed1998

Mobilization of peripheral blood progenitor cells by disease-specific chemotherapy in patients with soft tissue sarcoma.

We investigated peripheral blood progenitor cell (PBPC) mobilization by disease-specific chemotherapy in patients with metastatic soft tissue sarcoma (STS). Nine patients, five females and four males, aged 12-51 years, pretreated by one to nine courses of cytotoxic chemotherapy, underwent STS-specific mobilization followed by G-CSF at 5 microg/kg/day. PBPC were collected by 19 conventional-volume aphereses (8-12 l) with one to four procedures in individual patients. Leukaphereses started on median day 15 (range 13-18) from the first day of mobilization chemotherapy at medians of 25.8 x 10(3) WBC/microl (6.8-46.9), 3.5 x 10(3) MNC/microl (1.1-8.8), 122 x 10(3) platelets/microl (72-293) and 30.7 CD34+ cells/microl (6.7-207.8). Cumulative harvests resulted in medians of 4.6 x 10(8) MNC/kg (3.0-6.4), 2.9 x 10(6) CD34+ cells/kg (1.1-11.1) and 12.0 x 10(4) CFU-GM/kg (2.0-37.8). Eight patients underwent high-dose chemotherapy (HDCT) followed by PBPC rescue. Seven patients recovered hematopoiesis at medians of 12 days (8-15) for ANC >0.5 x 10(3)/microl and 14 days (8-27) for platelets >20 x 10(3)/microl. One patient, who received 1.6 x 10(6) CD34+ cells/kg, exhibited delayed ANC recovery on day +37 and failed to recover platelets until hospital discharge on day +55. We conclude that in patients with metastatic STS, who are pretreated by standard chemotherapy, PBPC can be mobilized by a further course of STS-specific chemotherapy plus G-CSF. One to four conventional-volume aphereses result in PBPC autografts that can serve as hematopoietic rescue for patients scheduled for HDCT.

Adolescent↗
PubMed1998

Treatment options for clinically recognized disseminated intravascular coagulation.

Current concepts of etiology and pathophysiology resulting in disseminated intravascular coagulation (DIC) form the basis of treatment of this hemostatic disorder. Due to the heterogeneous triggering diseases and different kinds of DIC, clinical symptoms such as predominant bleeding, thromboembolic complications or organ failure, clinical experience together with the profile of laboratory test results and their development over time provide the basis for the individually tailored treatment strategy. The guiding principle of therapy is to identify and vigorously treat the underlying cause of DIC without delay. Treatment options to correct the hemostatic defect and to dampen the intravascular clotting/fibrinolytic process include transfusion of blood products, heparin, antithrombin III, and antifibrinolytic agents. The availability of new drugs such as activated protein C, tissue factor pathway inhibitor, hirudin, or synthetic serine protease inhibitors, and the upcoming trials investigating the role of these and older treatment options will help us to more clearly recommend therapy in DIC of different etiology.

Animals↗
PubMed1998

Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: a phase II clinical trial.

OBJECTIVE: A prospective phase II study was performed to determine the feasibility and efficacy in terms of response rate, resectability, and morbidity in patients with locally advanced rectal cancer who received preoperative regional hyperthermia combined with radiochemotherapy (HRCT). SUMMARY BACKGROUND DATA: Recent studies suggest that preoperative radiochemotherapy in locally advanced rectal cancer can induce downstaging, but after resection the incidence of local recurrences remains high. Hyperthermia (HT) may add tumoricidal effects and improve the efficacy of radiochemotherapy in a trimodal approach. PATIENTS AND METHODS: Thirty-seven patients with histologically proven rectal cancer and T3 or T4 lesions, as determined by endorectal ultrasound and computed tomography, entered the trial. 5-Fluorouracil (300-350 mg/m2) and leucovorin (50 mg) were administered on days 1 to 5 and 22 to 26. Regional HT using the SIGMA 60 applicator (BSD-2000) was given once a week before radiotherapy (45 Gy with 1.8-Gy fractions for 5 weeks). Surgery followed 4 to 6 weeks after completion of HRCT. RESULTS: Preoperative treatment was generally well tolerated, with 16% of patients developing grade III toxicity. No grade IV complications were observed. The overall resectability rate was 32 of 36 patients (89%), and 31 resection specimens had negative margins (R0). One patient refused surgery. In 5 patients (14%), the histopathologic report confirmed no evidence of residual tumor (pCR). A partial remission (PR) was observed in 17 patients (46%). The survival rate after 38 months was 86%. In none of the patients was local recurrence detected after R0(L), but five patients developed distant metastases. CONCLUSION: Preoperative HRCT is feasible and effective and may contribute to locoregional tumor control of advanced rectal cancer, which is to be proven in an ongoing phase III trial.

Adenocarcinoma↗
PubMed1998

[Effectiveness of preoperative radio-chemo-thermotherapy with respect to thermometry in locally advanced rectal carcinoma].

Additional hyperthermia is able to intensify the effect of radio-chemotherapy in locally advanced rectal cancer. The datas represents favourable locally effect, if the necessary parameters of thermometry are achieved. We could demonstrate a correlation between temperatures and downstaging of the primary tumor. Consequently, aim of further developments is to optimize hyperthermia technology.

Combined Modality Therapy↗
PubMed1997

[A phase-I/II study on the local hyperthermia of cervical N2/N3 lymph node metastases].

BACKGROUND: Patients with advanced lymph node metastases from head and neck tumors at stage N2/N3 (i.e. UICC IV) present a difficult therapeutic problem. Despite combined radio-chemotherapy and hyperfractionated and/or accelerated fractionation regimens, local control of these tumors remains unsatisfactory. For this reason, the value of local radio wave/microwave hyperthermia was examined for this patient group in a phase I/II study.

Adult↗
PubMed1997

Leukocyte depletion and storage of single-donor platelet concentrates.

BACKGROUND AND OBJECTIVES: Because of widespread use of leukocyte reduction in platelet concentrates (PCs) and the need to store such concentrates, we investigated the effects of leukocyte depletion on the quality of stored PCs. MATERIALS AND METHODS: Ten double-sized PCs were divided into 2 equal units which were tested simultaneously. One half was stored for 5 days after filtration through a polyester filter, the other one was stored unfiltered. RESULTS: The volume of the 10 "oversized' PCs was 483 +/- 40 ml (mean +/- standard deviation) and they contained 5.9 +/- 1.5 x 10(11) platelets and 80 +/- 23 x 10(6) leukocytes. Filtration significantly reduced the leukocyte concentration (168 +/- 56/microliter before, 6 +/- 4 /microliter after filtration) and leukocyte count (39.9 +/- 11.3 x 10(6) vs. 1.3 +/- 0.9 x 10(6); p < 0.0005). Filtration caused a platelet loss of 16%, the platelet count decreasing not significantly from 2.91 +/- 0.75 x 10(11) to 2.40 +/- 0.94 x 10(11) (p = 0.26). After 5 days of storage all parameters of platelet function (platelet aggregation to several stimuli, hypotonic shock reaction [HSR] and platelet retraction), mean platelet volume, and pH and pCO2 showed no advantage for PCs filtered prior to storage compared to PCs stored unfiltered. Moreover, platelet aggregation on day 5 using 4 agonists at 10 concentrations showed worse results in 4 assays in prestorage filtered PCs (collagen [4 micrograms/ml: p < 0.05, ADP [0.2 mM]: p < 0.05, ADP [0.3 mM]: p < 0.05, thrombin [0.6 E/ml]: p < 0.05). But there is no convincing trend in all aggregation tests, and HSR, presumably the most useful parameter, was not different or day 5. CONCLUSIONS: There is no advantage in terms of improved quality for prestorage leuko-depletion of PCs. Taking into account the obvious disadvantages of filtration, such as platelet loss and increasing costs per transfusion, we conclude that pre- or post-storage filtration of single-donor PCs should be done only for patients who have a clear indication for the transfusion of leukocyte-poor blood products.

Blood Donors↗
PubMed1997

Global and extended coagulation monitoring during extracorporeal lung assist with heparin-coated systems in ARDS patients.

Heparin-coated systems for extracorporeal lung-assist (ECLA) were developed to reduce hemorrhagic risk by lowering the systemic heparinization, monitored by global tests, e.g. activated coagulation time (ACT) and activated partial thromboplastin time (APTT). Since this strategy gives no insight into procoagulant states, five ARDS patients receiving ECLA with heparin-coated systems were investivated for changes in coagulation using both global and extended tests. During ECLA onset the APTT and ACT were within or near normal ranges, platelets decreased 76.5% within 48 h, fibrinogen decreased 28.7%, thrombin-antithrombin-III complexes were elevated before ECLA (53 micrograms/L), but demonstrated an additional peak (238 micrograms/L), plasminogen-activator-inhibitor-1 increased 12-fold, and the C1-inhibitor dropped 14.1%. In conclusion, after the onset of ECLA from a previous prethrombotic state, the precoagulant, anticoagulant, fibrinolytic and complement systems were activated in a similar way to that reported for non-heparinized systems with high-dose heparin. This was however only monitored by an extended test panel which was unable to predict thromboembolic events during ECLA.

Adult↗
PubMed1997

Allele-specific PCR amplification of factor V Leiden to identify patients at risk for thromboembolism.

Resistance to activated protein C is the most common hereditary cause of thrombophilia and is significantly linked to factor V Leiden. We designed primers in order to identify factor V Leiden by allele-specific PCR amplification. Amplification specificity for factor V was ensured by a 3' primer located at the intron 9/exon 10 border of the gene. One sense and two antisense primers were used in two separate primer mixes specific for factor V ARG506 (wild-type) or factor V GLN506 (factor V Leiden). In each PCR reaction a pair of primers amplifying a fragment of the human growth hormone gene was included as an internal positive amplification control. The presence or absence of specific PCR amplification allowed definite allele assignment without the need for any postamplification specificity step. The internal positive control primers indicate a successful PCR amplification, allowing the assignment of homozygosity. In a prospective study 126 patients with thromboembolic events were analyzed using this technique and PCR-RFLP. The concordance between these methods was 100%. In 27 patients a heterozygous factor V GLN506 mutation was detected, whereas 1 patient with recurrent thromboembolism was homozygous. No false-positive or false-negative results were observed in the homozygous as well as heterozygous samples. Additionally, in 15 samples identified to carry the point mutation by allele-specific PCR amplification, automatic sequencing has confirmed the heterozygous or homozygous point mutation. Due to its time- and cost-saving features allele-specific amplification should be considered for screening of factor V Leiden.

Alleles↗
PubMed1996

Clinical experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors.

Anticancer drugs reversibly bound to magnetic fluids (ferrofluids) could be concentrated in locally advanced tumors by magnetic fields that are arranged at the tumor surface outside of the organism. If certain requirements are met, systemic toxicity might be minimized, and local tumor efficacy might be increased. We have conducted a Phase I clinical trial using this approach in patients with advanced and unsuccessfully pretreated cancers or sarcomas. Nine such patients received two treatment courses, 3 patients received one course, and 2 patients received three courses of magnetic drug targeting consisting of the infusion of epirubicin in increasing doses (from 5 to 100 mg/m2) that had been chemically bound to a magnetic fluid and the application of magnetic fields to the tumors for 60-120 min. In 2 of 14 patients, the same dose of epirubicin not bound to a magnetic fluid was administered systemically 3 weeks after drug targeting for intraindividual comparisons. Magnetic drug targeting with epirubicin was well tolerated. In one case, a planned second treatment was withdrawn, because of an episode of chills 130 min after infusion of the magnetic drug. Two patients received a third treatment because of good responses after the first two therapies. Based on magnetic resonance tomographic techniques, pharmacokinetics, and the histological detection of magnetites, it was shown that the ferrofluid could be successfully directed to the tumors in about one-half of the patients. Organ toxicity did not increase with the treatment, but epirubicin-associated toxicity appeared at doses greater than 50 mg/m2. Although treatment with magnetic drug targeting seems safe, improvements are necessary to make it more effective and independent of patient- or disease-related problems. A study design to compare conventional treatments with the new treatment form within one patient seems crucial to eliminate interindividual differences.

Adolescent↗
PubMed1996

Preclinical experiences with magnetic drug targeting: tolerance and efficacy.

Although site-specific direction of drugs within an organism would benefit patients with many diseases, active drug targeting is clinically not yet possible. To overcome some of the problems associated with active drug targeting, we have developed a magnetic fluid to which drugs, cytokines, and other molecules can be chemically bound to enable those agents to be directed within an organism by high-energy magnetic fields. In the first part of this study, various concentrations of the magnetic fluid were tested in rats and immunosuppressed nude mice with regard to subjective and objective tolerance. In the second part, the same parameters were evaluated after administration of the ferrofluid to which epirubicin (4'-epidoxorubicin) was chemically bound. Finally, two forms of therapy with the magnetic fluid were tested: tumor treatment by mechanical occlusion with the ferrofluid in high concentrations; and magnetic drug targeting, using small amounts of the ferrofluid as a vehicle to concentrate epirubicin locally in tumors. As a result, the ferrofluid did not cause major laboratory abnormalities; there was no LD50. With very high concentrations of the ferrofluid, animals showed lethargy for 1-2 days. There were no intolerances with the epirubicin-bound ferrofluid as well. Both forms of treatment led to complete tumor responses in an experimental human kidney as well as in a xenotransplanted colon carcinoma model. Thus, the magnetic fluid is a safe agent, which can be used in different ways for local forms of cancer treatment in conjunction with high-energy magnetic fields.

Animals↗
PubMed1996

Local hyperthermia of N2/N3 cervical lymph node metastases: correlationof technical/thermal parameters and response.

PURPOSE: Patients with advanced head and neck carcinomas, primarily nonresectable as well as recurrent cases, were treated in multimodality regimens with radiotherapy, chemotherapy, and local hyperthermia. Commercially available microwave and radiowave applicators were used in 50 patients with N2/N3 cervical lymph node metastases during more than 250 heat treatments. To assess technical suitability, the achieved power densities and thermal parameters were tested for correlation with anatomical and geometrical factors. To assess effectiveness, the response was compared with derived parameters of the achieved temperature distributions. METHODS AND MATERIALS: The temperature measurement points (in thermometry catheters) documented by computerized tomography are labeled according to tissue depth, shielding by osseous structures, and location in relation to the external applicators. Relative and absolute specific absorption rates (SAR) and cooling coefficients are extracted from the temperature-time curves. Time-averaged temperature-position curves are evaluated to obtain index temperatures (T90, T50, T20), minimum/maximum tumor temperatures, cumulative minutes T90 > or = 43 degrees C, and 43 degrees C-equivalent min T90. Radiation dose, treatment time, and chemotherapy regiment are also considered. A response parameter is defined using the pre- and posttherapeutic tumor volumes. A multivariate variance analysis is performed for the dependent variables power density, thermal parameters, and response. RESULTS: A significant correlation exists between power density and absorption, presence of a fat layer, and applicator illumination. The maximum depth is 5 cm, where SAR of >= 10 mW/g are registered. Achieved temperatures at individual measurement points are dependent on the SAR, and to a lesser extent, the perfusion-dependent cooling coefficients, but the index temperature T90 is only significantly related to intratumorally achieved SAR. The thermal gradient (T20-T50) and temperature peak (T20) are significantly influenced by the tumor volume. The response is directly related to the index temperature T90, equivalent minute T90 43 degrees C, and cumulative minutes T90 > or = 40.5 degrees C, and inversely related to the tumor volume. CONCLUSIONS: Local hyperthermia using microwave and radiowave applicators in the head and neck region is a tolerable and clinically practical supplementary therapy used as part of multimodal regimens, and has already been proven to be effective. However, the analyses also demonstrated the limits of currently available technology, and confirm the need for continued methodical research.

Adult↗
PubMed1996

Hyperthermia in the multimodal therapy of advanced rectal carcinomas.

The synergistic effects of hyperthermia (raising temperatures to 40 degrees C and above) when combined with radiotherapy and cytotoxic drugs and a modulation of immunological phenomena have been demonstrated in the laboratory. Pre-clinical data relating to hyperthermia are summed up, along with their implications for clinical application. Controlled studies of local and regional hyperthermia have been performed during recent years, and these show us that the adjunction of hyperthermia provides at least an improvement of local control compared with radiotherapy alone. Current clinical results are summarized. Therapy systems based on radiowave irradiation have been commercially available for regional hyperthermia of the pelvis since the mid 1980s. This technology allows us to perform sufficiently tolerable and effective regional hyperthermia on rectal carcinomas. Used as part of curative preoperative and postoperative multimodal therapeutic strategies, hyperthermia can lead to improvement in local control (resectability, down-staging, progression-free time, recurrence rate), at least for certain risk groups. The preoperative radio-chemo-thermotherapy of advanced primary and recurring rectal carcinoma, uT3/4, was tested in a phase-I/II study of 20 patients. Therapy procedure, acute toxicity, thermal parameters, and response are described and discussed for this patient group. The regimen proved to be sufficiently tolerable, and complications did not occur. Tumor resection was performed on 14 of the 20 patients; 13 of the procedures were R0-resections and one was an R2 resection. In 64% of the resected rectal carcinomas, histopathological down-staging of the pretherapeutic endosonographical stadium was achieved; in three of the patients, despite continued non-resectability, local control has now been maintained for more than 12 months. In two patients with nonresectable rectal carcinomas, local progress was seen during the neoadjuvant combination therapy.

Clinical Trials as Topic↗
PubMed1996

Chemotherapy for patients with adenocarcinoma of the pancreas.

Adenocarcinomas of the pancreas are diagnosed at an advanced, non-curable stage in most patients. In addition to local relapse or progression, distant metastases determine the poor prognosis, resulting in a median survival of less than 6 months in most studies of patients with locally advanced or metastatic pancreatic cancer. None of the cytotoxic drugs available show impressive activity in treatment of this disease. Therefore, chemotherapy is not recommended in pancreatic cancer. In selected cases, 5-fluorouracil-based therapy - with or without simultaneous radiation - may result in tumor responses. With a once-a-week outpatient protocol of folinic acid and 5-fluorouracil, we observed a progression-free period from 15 to 42 weeks in nine of 19 patients treated without any serious adverse effects, confirming reports of the weak, but well-tolerated activity of this combination. To alter the prognosis for patients with advanced adenocarcinomas of the pancreas, new drugs with more activity have to be developed and tested in well-designed trials.

Adenocarcinoma↗