Characteristics of cancer patients using homeopathy compared with those in conventional care: a cross-sectional study.

BACKGROUND: There are only few studies on cancer patients who are treated in complementary and alternative medicine clinics and comparing them with patients in conventional care. We will present the comparison of characteristics of two patient cohorts: one was treated in a homeopathic cancer care clinic and one was treated in a conventional oncology care (CC) outpatient clinic. PATIENTS AND METHODS: Six-hundred and forty-seven patients were included in this cross-sectional cohort study and had to fill in questionnaires [health-related quality of life (QoL) (Functional Assessment of Cancer Therapy-General Scale), depression and anxiety (Hospital Anxiety and Depression Scale), fatigue (Multidimensional Fatigue Inventory) and expectancies toward treatment]. Clinical data were extracted from medical records. This study presents the comparison of both cohorts. RESULTS: Patients in the homeopathy cohort are younger, better educated and more often employed than patients in the CC cohort. The most pronounced differences indicate longer disease histories and different diagnostic and clinical pretreatment variables. Despite the clinical differences, QoL as well as anxiety, depression and fatigue was similar in both the groups. CONCLUSIONS: Homeopathic treatment is sought by cancer patients at a different phase during the course of the disease, which has particular implications for research. However, expectancies toward the benefit of the treatment as well as QoL data are similar.

Cognitive deficits as long-term side-effects of adjuvant therapy in breast cancer patients: 'subjective' complaints and 'objective' neuropsychological test results.

OBJECTIVE: Various studies have demonstrated that neuropsychological deficits are potential side-effects of adjuvant therapy in breast cancer patients. To date, little is known about the long-term development of these deficits and their implications for patients' everyday life. METHODS: Within the framework of an intervention study, 90 breast cancer patients after adjuvant chemotherapy were examined at three measurement points. The focus of this article is on the cognitive status at the last measurement point (on average, 9 months after the end of oncological therapy) and, in particular, on the correlations between subjective self-appraisal and neuropsychological test results. RESULTS: Although the prevalence of neuropsychological deficits significantly decreased as time elapsed after the end of oncological therapy, 21% of our sample group still displayed indications of clinically relevant long-term cognitive deficits. A sub-group of severely affected patients showed specific deficits in verbal-semantic memory and judged their everyday cognitive performance as being extremely poor. CONCLUSION: The identification of verbal-semantic memory as a specific problem area has important implications on the planning of future studies with regard to both the examination of underlying pathophysiological mechanisms and the specific effects of these deficits on patients' self-appraisal.

Effects of specific neuropsychological training programs for breast cancer patients after adjuvant chemotherapy.

Neuropsychological deficits are among the negative side effects of adjuvant chemotherapy for breast cancer. We compared the effects of two types of neuropsychological interventions against a control group with no specific training in a total of 96 female in-patients undergoing oncological rehabilitation. Most results of a comprehensive neuropsychological test battery improved significantly during the patients' oncological rehabilitation in all three groups; we identified no specific intervention effects. We observed little overall correlation between the neuropsychological test results and the patients' own appraisals of their mental capacity. Clinically relevant neuropsychological deficits were still evident 6 months later in a small subgroup of patients.

Rehabilitation of therapy-related cognitive deficits in patients after hematopoietic stem cell transplantation.

Neuropsychological deficits are potential side effects of hematopoietic stem cell therapy (HSCT). Systematic data on the long-term course of and therapeutic options for these consequences are limited. One hundred fifty-seven patients were screened for cognitive deficits following HSCT for malignant diseases at an in-patient oncologic rehabilitation clinic. Patients showing evidence of impairment were randomly assigned to one of two training groups: individualized PC-supported training or neuropsychological group therapy. The control group consisted of patients who received no specific training. During in-patient rehabilitation, the results of a comprehensive neuropsychological test battery improved significantly in all three groups, and no specific intervention effects were identified. Neuropsychological deficits were still evident in a subgroup of patients 6 months later. Correlation between neuropsychological testing and patients' self-evaluation of cognitive functioning in daily life was generally low. Sustained attention and verbal-semantic memory played the main role for self-appraisal and in the designation as 'neuropsychologically impaired'. In conclusion, a substantial number of patients revealed evidence of cognitive deficits a long time after HSCT. There is a need for more studies and for the development of differentiated rehabilitative measures for such therapeutic consequences.

Sensitivity of leukemia cell lines to cytotoxic alkyl-lysophospholipids in relation to O-alkyl cleavage enzyme activities.

The human leukemia cell lines K562, HL60, and Raji and the mouse leukemia cell line L1210 showed a differential susceptibility to the action of the alkyl-lysophospholipid (ALP) 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3). After 48 hours, the 50% growth-inhibition doses (ID50) of ET-18-OCH3 were found to be 0.78 microgram/ml (HL60), 1.53 microgram/ml (Raji), 4.41 micrograms/ml (K562), and 5.05 micrograms/ml (L1210), as determined by [3H]thymidine incorporation. At the same time, cell viability was determined by trypan blue exclusion and revealed median lethal doses (LD50) of 3.5 micrograms/ml (HL60), 15 micrograms/ml (Raji), 24 micrograms/ml (L1210), and 38 micrograms/ml (K562). Since O-alkyl cleavage enzyme previously was suggested as being important in the detoxification of cytotoxic ALPs, the enzyme activity was compared with the susceptibility to ET-18-OCH3 in the distinct cell lines. In comparison to an approximate sevenfold to elevenfold (ID50 and LD50, respectively) difference in the susceptibility of the above leukemia cell lines to ET-18-OCH3, no significant difference in the specific activities (0.13-0.21 nmol/min/mg) of the O-alkyl cleavage enzyme was found in the above leukemia cell lines. Therefore, the differential sensitivity of the above lines investigated cannot be explained by differences in O-alkyl cleavage enzyme activity. Experiments with radiolabeled ET-18-OCH3 in Raji cells suggest, rather, a critical role for phospholipases C and/or D in ALP metabolism.

Crystal structure of bovine beta-trypsin at 1.5 A resolution in a crystal form with low molecular packing density. Active site geometry, ion pairs and solvent structure.

The crystal structure of bovine pancreatic beta-trypsin (BPT) has been determined from a novel orthorhombic crystal form which contains substantially more solvent (filling 57% of the volume of the unit cell) than previously determined orthorhombic (44%) and trigonal (37%) BPT structures. The native and benzamidine-inhibited crystal structures of BPT in ammonium sulphate at pH 5.3 have been determined for the new form by molecular replacement techniques. The structures have been refined at 1.5 A resolution with final R-values of 16.7% and 16.9%, respectively. Comparison with the previously refined old orthorhombic forms shows that the overall conformation of the protein backbone is highly conserved. A great number of previously undefined side-chains have been located in density. At the C terminus an extra ion pair involving lysines 87 and 107 has been revealed. A far more detailed picture of the ordered solvent structure has been derived. Thirty water clusters have been identified. A large water network extends from the calcium binding site to the activation area and the autolysis loop. There is evidence for a water channel reaching from the depth of the specificity pocket to the nearby protein surface which might be involved in the displacement of water molecules upon substrate binding. A sulphate anion which forms hydrogen bonds to the active site residues His57, Ser195 and Gly193 was for the first time positioned in clearly defined electron density. Interaction with the sulphate ion may explain the increase in the pKa value of His57 at high sulphate concentrations which was observed by nuclear magnetic resonance studies of a bacterial serine protease both in crystalline form and in solution. Thus, a His-Ser hydrogen bond will not exist in solvents containing sulphate at low pH (up to at least 6.8) where the imidazole of His57 is protonated. The new crystal form is of considerable interest for substrate binding studies. Wide solvent channels should allow diffusion of large substrates (comparable in size to, e.g. pancreatic trypsin inhibitor) into the enzyme crystal. The active site is accessible; intermolecular contact areas are further remote from the active site than in the old orthorhombic form.

Cognitive dysfunction and subjective complaints of cancer patients. a cross-sectional study in a cancer rehabilitation centre.

Although the neurotoxicity of many anticancer therapies is well documented, the impact of cancer treatment on cognitive functioning has been studied less frequently. The present study examines deficits in cognitive functioning and their correlation with medical data as well as with psychosocial variables. A standardised neuropsychological test battery and several questionnaires were administered to a random sample of 119 patients. 24% of our patients fulfilled our criterion for cognitive impairment. There were no significant associations between the results of the neuropsychological testing and the current affective status or self-reports of attentional deficits in daily life. Cognitive impairment occurs in a clinically relevant percentage of cancer patients and cannot be explained exclusively due to depression or anxiety. Since subjective and objective cognitive impairment data showed little correlation, neuropsychological evaluation should not only be based on subjectively-reported complaints, but also on objective measurements.

IFN-gamma receptors on human tumor cells: relationship between receptor ligand interactions and induction of IFN-gamma response.

Scatchard analysis of 125I-IFN-gamma binding on fresh lymphoid and myeloid tumor cells derived from 34 leukemia patients and on normal cells obtained from 14 healthy individuals revealed similar high affinity binding with a mean Kd of around 2 X 10(-11) M in 14/14 normal and 30/34 malignant cells, but large quantitative differences in the receptor number of malignant cells with a range of 300 to 12,000 receptors/cell. In contrast, normal lymphoid and myeloid cells expressed consistantly low numbers of receptors with a mean of 300 and 1,000 receptors/cell, respectively. Kinetic studies of IFN-gamma binding in relation to induction of HLA-DR antigens in established cell lines revealed the existence of close correlations between the quantity of receptor ligand interaction and induction of IFN-gamma response, indicating that at limiting IFN-gamma concentrations the height of response is controlled by the number of expressed membrane receptors. In the light of the observed quantitative differences in IFN-gamma receptors on various tumors, this finding may have implications for the definition of therapeutically effective IFN-gamma doses.

Rubella virus antigen in lymphocytes of patients with angioimmunoblastic lymphadenopathy (AIL).

Lymph node sections from 14 patients with angioimmunoblastic lymphadenopathy (AIL) were incubated with fluorescein-labeled specific antiserum against rubella virus antigen. In lymphoid cells from 11 patients intracytoplasmic rubella antigen was demonstrated. The results support the idea of a persistent virus infection in AIL.

Intra-arterial perfusion therapy with 5-fluorouracil in patients with metastatic colorectal carcinoma and intractable pelvic pain.

In a phase-II trial, 18 patients with intractable pelvic and perineal pain caused by local recurrent and/or metastatic colorectal carcinoma resistant to combinations of analgesics, systemic cytostatic chemotherapy and/or radiation were treated with intra-arterial perfusion therapy using 15-30 mg 5-FU/kg body wt./day for 1-5 days. Of 18 patients, ten achieved complete pain relief for 3-32 weeks (mean, 15.7 weeks); after the perfusion therapy eight used less than 50% of the amount of analgesics required before treatment; one patient had only a minor response; two patients were treated unsuccessfully. Side effects were mild and controllable. One patient died subsequent to arterial embolism in the leg where the catheter was placed; pelvic perfusion therefore appears risky in patients with severe arteriosclerosis.

Accuracy in Laue X-ray diffraction analysis of protein structures.

The accuracy in protein structure analysis based on Laue X-ray diffraction has been investigated for the example of two orthorhombic structures of bovine pancreatic trypsin (BPT). The precision in the Laue structure factors and the contrast in electron-density maps were used as criteria. A comparison with the results of previous analyses based on conventional crystal rotation methods showed that high resolution around 1.4 A may be reached with both monochromatic and polychromatic techniques. Electron-density maps exhibited significantly lower contrast when calculated on the basis of Laue structure amplitudes, due to inefficient exploration of reciprocal space at low resolution by the Laue method even in the case of a broad bandwidth and inclusion of exposures from several different crystal orientations. Laue data were recorded on photographic film and processed using the program LAUEMAD [Bartunik & Borchert (1989). Acta Cryst. A45, 718-726]. The empirically derived wavelength scaling factors based on a comparison of equivalent reflection intensities were in good agreement with theoretical estimates over a broad wavelength range. One BPT structure was refined on the basis of Laue structure amplitudes (current R factor 24% at 1.8 A resolution).

[Pharmaceutical comparability of different therapeutic Echinacea preperations]. / Zur pharmazeutischen Vergleichbarkeit von therapeutisch verwendeten Echinacea-Präparaten.

Cichoric acid and Dodeca 2E, 4E, 8Z, 10E/Z-tetraenoic acid isobutylamide (alkamides 8, 9) are described as immunomodulating active components of Echinacea. We quantified both substances in 25 Echinacea-containing remedies customary in trade. Concerning both active components, we found highly concentrated remedies as well as remedies without any detectable cichoric acid or alkamides. The concentration of both active components varied extremely depending on the type of remedy (homeopathic mother tincture, pressed juice, tablets, spagyric tincture), on the Echinacea-species (Echinacea angustifolia, Echinacea pallida, Echinacea purpurea) and on the part of the plant (root, herb, whole plant). Moreover, we found large differences between comparable drugs of different manufacturers and between different charges of the same remedy. We recommend that preclinical and clinical studies with Echinacea-containing drugs should always include the quantification of the potentially active components. We are convinced, that in the long term this will help to clarify how the different active components contribute to the immunomodulating effect of Echinacea.

[What is the benefit of oncological rehabilitation programs for cancer patients in palliative care?]. / Was können onkologische Rehabilitationsstrategien für Tumorpatienten in palliativen Erkrankungssituationen leisten?

Medical and psychosocial rehabilitation of cancer patients is deeply integrated into the German health system. In contrast to the majority of other European countries and the United States of America, rehabilitation is mainly done as inpatient care and only rarely in outpatient units. In curative treated cancer patients the main goals of rehabilitation include recovery from physical impairments, adaptation to functional disabilities and improvement of psychosocial functioning, including the ability to go back to work. In palliative cancer patients the improvement of health adjusted quality of life, the avoidance of permanent supportive care and the social integration are the major goals. Cancer rehabilitation needs an interdisciplinary strategy between medical, psychooncologic, physiotherapeutical and educational professionals. To attain a benefit for the individual cancer patient as well as for the medical system it is important to clearly define the rehabilitation needs and design a most individual rehabilitation program adjusted to the personal needs of the patient. A systematic quality management since 1995 of German rehabilitation clinics and rehabilitation programs did significantly improve this part of the professional health system. However it is necessary to add more outpatient units for cancer rehabilitation to reach more flexibility and satisfy the demand of patients for more home located support.

Chemotherapy-induced peripheral neuropathy in cancer patients: a four-arm randomized trial on the effectiveness of electroacupuncture.

Purpose. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting side effect of cytostatic drugs. Since there are no proven therapeutic procedures against CIPN, we were interested to define the role of electroacupuncture (EA) from which preliminary data showed promising results. Methods. In a randomized trial with a group sequential adaptive design in patients with CIPN, we compared EA (LV3, SP9, GB41, GB34, LI4, LI11, SI3, and HT3; n = 14) with hydroelectric baths (HB, n = 14), vitamin B1/B6 capsules (300/300 mg daily; VitB, n = 15), and placebo capsules (n = 17). The statistical power in this trial was primarily calculated for proving EA only, so results of HB and VitB are pilot data. Results. CIPN complaints improved by 0.8 ± 1.2 (EA), 1.7 ± 1.7 (HB), 1.6 ± 2.0 (VitB), and 1.3 ± 1.3 points (placebo) on a 10-point numeric rating scale without significant difference between treatment groups or placebo. In addition no significant differences in sensory nerve conduction studies or quality of life (EORTC QLQ-C30) were found. Conclusions. The used EA concept, HB, and VitB were not superior to placebo. Since, contrary to our results, studies with different acupuncture concepts showed a positive effect on CIPN, the effect of acupuncture on CIPN remains unclear. Further randomized, placebo controlled studies seem necessary. This trial is registered with DRKS00004448.

[Process quality in oncologic rehabilitation. Viewpoint of the Professional Committee of Rehabilitation, After-care and Social Medicine of the German Cancer Society]. / Zur Prozessqualität in der onkologischen Rehabilitation. Die Sichtweise der Arbeitsgemeinschaft für Rehabilitation, Nachsorge und Sozialmedizin in der Deutschen Krebsgesellschaft (ARNS).

The article concerns itself with the issue of process quality in inpatient institutions for oncological rehabilitation and expresses the viewpoint of the German Cancer Society's Section for Rehabilitation, Aftercare and Social Medicine (ARNS). Standards for the organization of patients' access to the rehabilitation clinic, for the design of oncological-rehabilitational diagnostics, for the formation of therapeutic strategies and the rehabilitative services offered will be described.

Cancer-related fatigue in patients attending oncological rehabilitation programs: prevalence, patterns and predictors.

BACKGROUND: Fatigue is one of the most frequent symptoms in cancer patients. It is the aim of medical and psychosocial rehabilitation programs to reduce physical impairments and psychosocial distress. There are no reliable data on the prevalence or the pattern of fatigue in patients attending such rehabilitation programs. We therefore initiated a cross-sectional study to evaluate this phenomenon. PATIENTS AND METHODS: Using the EORTC QLQ-C30, HADS and MFI questionnaires in 144 patients with different malignant diseases the incidence, patterns and necessity of treatment of fatigue were evaluated. RESULTS: One third of the patients were diagnosed with breast cancer, 27% with gastrointestinal cancers and 20% suffered from haematologic/lymphatic diseases. There was a good correlation between fatigue levels in the 3 instruments used. 22% of all patients showed significant symptoms of fatigue. The univariate analysis did not reflect any significant differences in severity of fatigue with respect to diagnosis, haemoglobin levels, medical and therapeutic history or sociodemographic data. However, using cluster analysis we could identify 3 groups of patients that differ significantly in fatigue and quality-of-life measurements. CONCLUSION: We conclude from our data that fatigue is an important phenomenon in cancer patients who attend medical and psychosocial rehabilitation programs. This has an impact on the ability and degree to reintegrate these patients into everyday life.

[Mitomycin C and high-dosage medroxyprogesterone acetate in the therapy of metastasizing breast cancer. Results of a phase II study of the Workshop for Internal Oncology of the German Cancer Association]. / Mitomycin C und hochdosiertes Medroxyprogesteronacetat in der Therapie des metastasierenden Mammakarzinoms Ergebnisse einer Phase-II-Studie der AIO.

Combination therapy of mitomycin C 40 mg/m2 and medroxyprogesterone acetate 1.500 mg/day in patients with refractory metastatic breast cancer was tested within a phase II trial of the AIO. The overall response was 50% with 2 complete and 12 partial remissions. This combination therapy was tolerated well and hematologic toxicity was less than expected. More often pulmonary and renal toxicity appeared. This combination schedule seems to be useful even in patients with pretreated metastatic breast cancer. Hematologic, pulmonary and renal functions have to be observed.