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Biomedical subjects

M Sieber

Publications and source records attributed to M Sieber.

At least 73 records · Page 4Linked to original sources

Hodgkin's disease. Treatment of intermediate stages.

Intermediate stage Hodgkin's disease (HD) is defined as nodal disease with certain clinical risk factors. Patients with intermediate stage HD qualify for a combination of chemo- and radiotherapy, since radiotherapy alone results in a high relapse rate. The precise definition of this group varies between trial groups. It is generally believed that such patients should receive 4-6 cycles of modern multidrug chemotherapy and in addition radiotherapy of the involved field or the extended field. With modern combination therapy, about 70-80% of the patients in this group can be cured. However, the combination of the number of chemotherapy cycles, the field sizes and the dosage of radiation within these fields are not clear. Current clinical studies try to reduce radiation dose and field without compromising treatment efficacy in order to reduce late toxicities.

Combined Modality Therapy↗

Epidemiology of eating behaviour and weight distribution in 14- to 19-year-old Swiss students.

A sample consisting of 1944 Swiss students of both sexes was investigated with regard to distribution over weight categories based on BMI age percentiles and eating behaviour (EAT-26) in relation to age, sex and socio-economic status (SES). In addition, the relationship between BMI and Eating Attitudes Test scores was analysed. More subjects than expected were found to be in the obese weight categories. No clear effect of age and sex on the distribution of the sample across the five BMI classes was observed. There was an inverse relationship between BMI and socio-economic status. On the EAT scale girls scored twice as high as boys. Age had no effect on the EAT scores in females, although it did in males. Socio-economic status and EAT scores were inversely associated. Three risk categories based on the EAT scores were described: EAT 0-9 = no risk (77.5% girls, 93.0% boys), EAT 10-19 = low risk (14.1% girls, 5.5% boys), and EAT > or = 20 = high risk (8.3% girls, 1.5% boys). With regard to both aspects, weight and eating behaviour, female students showed more disturbed eating behaviour and fewer instances of deviation from normal weight. In male subjects there were more deviations from normal weight than instances of disturbed eating behaviour.

Adolescent↗

Report of the workshop on clinical trials. GHSG. German Hodgkin Study Group.

During the Third International Symposium, a leading panel of experts in the field discussed the current most prominent problems in the treatment of Hodgkin's disease to give recommendations for future clinical trials. Within the workshop on clinical trials the following issues were addressed: 1. Which diagnostic procedures are state of the art and to what extent are they able to contribute to a so-called response-adapted treatment (RAT)? 2. What is the optimal dose and volume of radiotherapy in different stages? 3. What is the value of chemotherapy in early stages and is it restricted to a certain subgroup? 3. Have we achieved as much as we can in intermediate stages in terms of response with now focusing future efforts on reducing toxicity and improving quality of live? 5. Is high-dose chemotherapy (HDCT) the answer to the challenge of improving treatment results in advanced stages? 6. What is the optimal schedule and dose of HDCT and consecutive autologous bone marrow transplantation (ABMT)?

Clinical Trials as Topic↗

Applications of impedance spectroscopy in biochemistry and biophysics.

The present study is intended to demonstrate the application of impedance spectroscopy to two very different fields of biophysical research. The core component of our measuring setup is a self-constructed continuous wave impedance spectrometer together with special measuring chambers which are individually designed for the systems under investigation. We directed our attention towards: i) the investigation of solid supported lipid bilayers in general, especially systems which are suitable for protein reconstitution such as dimethyldioctadecylammonium bromide (DODAB) immobilized onto a gold electrode, precovered with a negatively charged monolayer of 3-mercaptopropionic acid. Impedance spectroscopy allows to study the stability, the thickness and the electrode coverage of those artificial membranes as well as the observation of ion transport mediated by ionophores like gramicidin D incorporated into a DODAB-bilayer. ii) The characterization of the passive electrical properties of epithelial and endothelial cell monolayers in general and especially the determination of their transepithelial (transendothelial) electrical resistances as a measure for epithelial barrier function. From impedance spectra, as reported here, we are able to follow the formation and modulation of cell layer permeability to small ions.

Animals↗

DNA binding specificity of the basic-helix-loop-helix protein MASH-1.

Despite the high degree of sequence similarity in their basic-helix-loop-helix (BHLH) domains, MASH-1 and MyoD are involved in different biological processes. In order to define possible differences between the DNA binding specificities of these two proteins, we investigated the DNA binding properties of MASH-1 by circular dichroism spectroscopy and by electrophoretic mobility shift assays (EMSA). Upon binding to DNA, the BHLH domain of MASH-1 underwent a conformational change from a mainly unfolded to a largely alpha-helical form, and surprisingly, this change was independent of the specific DNA sequence. The same conformational transition could be induced by the addition of 20% 2,2,2-trifluoroethanol. The apparent dissociation constants (KD) of the complexes of full-length MASH-1 with various oligonucleotides were determined from half-saturation points in EMSAs. MASH-1 bound as a dimer to DNA sequences containing an E-box with high affinity KD = 1.4-4.1 x 10(-14) M2). However, the specificity of DNA binding was low. The dissociation constant for the complex between MASH-1 and the highest affinity E-box sequence (KD = 1.4 x 10(-14) M2) was only a factor of 10 smaller than for completely unrelated DNA sequences (KD = approximately 1 x 10(-13) M2). The DNA binding specificity of MASH-1 was not significantly increased by the formation of an heterodimer with the ubiquitous E12 protein. MASH-1 and MyoD displayed similar binding site preferences, suggesting that their different target gene specificities cannot be explained solely by differential DNA binding. An explanation for these findings is provided on the basis of the known crystal structure of the BHLH domain of MyoD.

Amino Acid Sequence↗

Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin's disease. German Hodgkins' Study Group (GHSG).

OBJECTIVE: It was the aim of this prospective randomized multicenter study to compare chemotherapy and radiotherapy as consolidation treatments in patients achieving complete remission (CR) after 6 cycles of doxorubicin-containing chemotherapy in advanced-stage Hodgkin's disease (HD). METHODS: A total of 288 previously untreated patients aged 18-60 years with stage IIIB or IV HD received induction chemotherapy with 3 X (COPP + ABVD). Patients achieving CR were eligible for randomisation to either 20 Gy radiotherapy to initially involved fields (RT-arm) or to an additional 1 X (Copp + ABVD) (CT-arm ). Patients with nodal PR were allocated to more intense radiotherapy (IRT-arm: 20 Gy IF, 40 Gy to persisting tumor). Four patients with persisting organ involvement after induction received salvage chemotherapy. RESULTS: Of 288 patients, 171 (59%) achieved CR after induction chemotherapy. Of these, 100 patients were successfully randomized to RT or CT. In the CT arm relapses were observed on 10 of 49 patients compared with 13 of 51 patients in the RT arm (p = n.s.). Fifty patients refused randomisation and for them a treatment was chosen, and 21 patients refused any further treatment. Of these 21 patients with no consolidation therapy, 9 relapsed, indicating an approximately 3-fold increased relapse risk compared with those receiving either of the consolidation therapies. No relapse was observed in initially involved lung or liver sites. Adverse prognostic factors for freedom from treatment failure and survival were low hemoglobin and large mediastinal mass at initial presentation. CONCLUSIONS: No statistically significant differences in treatment efficacy were detected between 20 Gy IF radiotherapy and 1X (COPP + ABVD) chemotherapy following CR after six cycles of alternating chemotherapy in patients with advanced-stage HD. However, limited observations in a non-randomized cohort indicate that patients without consolidation treatment of CR after 6 cycles of chemotherapy may have an elevated risk of relapse.

Adolescent↗

[Causal attributions and coping with illness by breast cancer patients: results of a longitudinal study].

The present 3-year longitudinal study investigated the relationship between causal attribution and coping mechanism. Data were collected in a group of 66 breast cancer patients by self-report questionnaires. Three issues were addressed: 1. How do the patients explain the cause of their illness? 2. Do the subjective causes change over the course of three years? 3. What kind of relationship can be found between the causal attributions and the coping mechanism of the patients? Results showed a predominance of psychological attribution. Only little statistical prove could be found for changes between the four ratings. Analysing the individual data of the patients however revealed changing perceptions for about half the patients. A relationship between psychological attribution and depressive coping and problem solving as well were found.

Adaptation, Psychological↗

[Sexual risk taking].

Unprotected vaginal and anal sex is the most important risk behavior. Prevention campaigns are more and more concentrated on heterosexuals because 71% of all HIV-infections worldwide are due to heterosexual contacts. The effects of different campaigns are discussed. The positive effect of HIV-test on risk reduction is not clearly demonstrated an negative effects (increased risk) after taking the test give rise to concerns. Risk reduction is the most practicable and realistic prevention strategy.

AIDS Serodiagnosis↗

[The adoption problem in treatment of a 15-year-old boy].

In a brief review of the literature, the typical psychological problems associated with adoption are summarized. There is a marked discrepancy between the positive prognosis for adoption seen in the prospective studies on the one hand and the often dubious outcome of clinical treatment on the other. Our case study suggests that the apparently ubiquitous "issue of adoption" needs other co-factors to become a "pathology of adoption". Clinical experience underlines the difficulty in and importance of finding an adequate therapeutic setting for severely disturbed adolescent adoptees: outpatient treatment is sometimes overtaxed by the tendency of the family to reject the adoptee and the noisy often dissocial behaviour of the adoptee, but an inpatient setting may repeat the trauma of separation, and often there is not a sufficient period of time for treatment. In this "therapeutic dilemma" where there is a high risk of personal relationships we see the need for a better connection between inpatient and outpatient treatment: The inpatient therapist should be able to continue treatment on an outpatient basis after the patient is discharged.

Adolescent↗

Anti-idiotype vaccine against Hodgkin's lymphoma: induction of B- and T-cell immunity across species barriers against CD30 antigen by murine monoclonal internal image antibodies.

Murine monoclonal antibody HRS-4 (Ab1), which defines the cell-bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti-idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS-4 were shown to be anti-idiotypic Ab2 beta carrying the internal image of the CD30 antigen. These antibodies bound specifically to HRS-4 and effectively inhibited binding of HRS-4 to a CD30 antigen preparation at concentrations as low as 50 ng/ml. KLH-coupled Ab2 beta 14G9 and 9G10 induced in BALB/c mice and New Zealand white rabbits a specific polyclonal humoral response against the 120 kDa band of the CD30 antigen. Moreover, BALB/c mice immunized i.p. with KLH-coupled 14G9 and 9G10 exhibited a statistically significant (p less than 0.01) delayed-type hypersensitivity reaction against CD30 expressing Hodgkin-derived L540-cells. We conclude from these data that Ab2 beta 14G9 and 9G10, mimicking structures of the nominal CD30 antigen, are capable of inducing a CD30-specific T-cell- and B-cell-mediated immune response in mice and even across species barriers in rabbits. These CD30 anti-id antibodies may hold promise for use as vaccines against CD30-antigen-expressing lymphomas.

Animals↗

Direct and indirect conversion of bull evaluations for yield traits between countries.

Genetic evaluations of Holstein bulls from the US were matched with Canadian, Italian, Mexican, and Netherlands evaluations for the same bulls. Conversion equations for milk yield were computed by least squares, Goddard, and Wilmink methods. Accuracy was assessed by splitting data and applying equations developed from one subset to the other subset. Methods were judged by mean differences between actual and converted evaluations and standard deviation of that difference. Imperfection of conversions appeared to be due to inherent characteristics (variation and bias) of data rather than to inadequacy of conversion methodology. Least squares was slightly better than other methods but is not recommended by the International Bull Evaluation Service. The Goddard method was generally superior to the Wilmink method, but data often are not available for its application. A variation of the Goddard method was equal in accuracy to the Wilmink method. Daughter yield deviation as both dependent and independent variables was examined for only one data set and was little different from the Goddard method. Indirect equations were quite accurate for US to Mexico and US to the Netherlands but much less accurate for US to Italy conversion. Indirect conversions still would be useful until evaluations of bulls in common allow for direct conversions. For all three countries, a variation on indirect methodology was slightly superior to the usual indirect equations.

Animals↗

Coping strategies and course of disease of breast cancer patients. Results of a 3-year longitudinal study.

In a prospective 3-year longitudinal study investigating correlations between coping strategies and course of breast cancer a consecutive series of 107 patients were assessed for biological and psychosocial data. Data analysis indicated no significant correlations between coping strategies and course of cancer. On the other hand, biological parameters such as size of tumor and lymph node stage at time of surgery correlated significantly with the course of disease. It was concluded that the assessed indicators of coping are of little importance in regard to the course of the disease and less predictive compared with somatical parameters of breast cancer.

Adaptation, Psychological↗

[Reliability and validity of the Zurich Questionnaire of Coping with Illness].

The coping behavior of three groups of patients (N = 585) was assessed by a 45-item-questionnaire, a revised version of the Zurich Coping Questionnaire (ZKV) published earlier. The following three coping patterns resulted, established by factor analysis: ZKV-1: Depressive coping (Cronbach-alpha = .86), ZKV-2: Self-encouragement/distraction (.81) and ZKV-3: Problem tackling (.60). Retest-stability for the two scales 1 and 3 was high (r greater than .74, 12-month-interval). Concurrent and prognostic validity was assessed. The results indicate that the ZKV is a useful instrument for coping research, especially for the prognostic rating of the subsequent coping behavior.

Adaptation, Psychological↗

[Positive and negative consequences of voluntary HIV-antibodies test].

Clinical observations and empirical findings with regard to possible negative and positive consequences of the HIV-Antibody-Test are discussed. It was concluded that at the present time we should not recommend the test generally for all people, but rather suggest the way of test-counselling. Results of a pilot study demonstrate that during anonymous testing a conversation about the preceding risk behavior is possible with most of the testes. Recent discussions about aids with the partner or close friends had an important trigger function in their decision to ask for the HIV-Antibody-Test.

AIDS Serodiagnosis↗

[The significance of psychosocial factors for the course of breast cancer--results of a prospective follow-up study].

The meaning of psychosocial factors for the course of breast cancer--First results of a prospective research project. Studies investigating the meaning of psychosocial factors for the course of cancerous diseases have so far been contradictious. In this paper the basic datas and first results of a prospective research project on this topic covering 107 breast cancer patients are reported. Somatic datas such as stage of lymph-nodes, type of surgery and additional treatments (radiation therapy or chemotherapy), are less important for the coping process 6 months after primary treatment than the cognitive attitudes of the patients toward their disease. About 56 percent of the patients coped quite well with their disease, 44 percent showed difficulties. The group of patients whose somatic and psychosocial prognosis was judged rather unfavorably at the time of the first examination, showed the highest rate of recidivation and progredience in the follow-up of the first 12 months.

Adaptation, Psychological↗