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Biomedical subjects

M Probst

Publications and source records attributed to M Probst.

At least 55 records · Page 3Linked to original sources

Body composition in female anorexia nervosa patients.

For the first time, body composition has been studied in a very large sample of female anorexia nervosa patients (n 200) using two methods: anthropometry (skinfold thickness) and densitometry (underwater weighing). The concurrent validity of both methods appeared to be good (r 0.84). Although the mean percentage of body fat (13.5) in our sample corresponds with most of the previous reports, the range (4.3-24.8) is great. Our study shows that BMI is not a good measure of fatness. Age and duration of illness were not related to body fat. Percentage fat was found to be different (t 2.76, P < 0.01) according to the diagnostic subtype of anorexia nervosa: restricters (12.9) v. bingers and/or purgers (14.7).

Adipose Tissue↗

Linomide and interleukin-2 in patients with advanced renal cell carcinoma.

Quinoline-3-carboxamide (Linomide) is a novel, synthetic immunomodulator acting via immunologic and non-immunologic mechanisms. It has shown efficacy against various malignancies, experimental autoimmune encephalomyelitis, and septic shock in animal models and has been investigated for clinical use in minimal residual myeloid leukemia with promising results. Interleukin-2 has shown considerable efficacy in palliative anti-tumor-treatment of advanced renal cell cancer, revealing remission rates of up to 40% in combination therapy regimens. Linomide is reported to exhibit synergistic effects with interleukin-2. Here we report on a clinical phase I/II study examining tolerance and efficacy of a combination therapy schedule of SQ interleukin-2 and PO Linomide in advanced renal cell cancer. Seventeen patients received 10 IU/m2 interleukin-2 per week for 8 weeks, resting interleukin-2 for another 8 weeks. In week 5 they started 5 mg Linomide daily, continued with 10 mg from week 7 to 16. No objective remissions were observed. Among 15 patients evaluable for response, 10 (66.7%) were progredient during the study. Three patients died during the observation period, including two not evaluable for response. Median survival was 4.0 months, median progression-free survival 2.5 months with a Kaplan-Meier estimate of 3.63 months. Fever, reduced general condition, nausea/vomiting, dyspnea, anorexia, chills and hypotension were the most common side effects, reaching WHO grade 3 in 6 and grade 4 in 2 cases. In summary, Linomide in combination with interleukin-2 provides no advantages in efficacy or toxicity over other therapy regimens employing interleukin-2.

Adjuvants, Immunologic↗

[A new technique for implantation of venous port systems].

A new method of implantation of venous port systems is described. The advantage is very safe placement of the catheter with an intra-atrial ECG lead. A special transducer system allows control of the catheter tip.

Catheterization, Central Venous↗

Exposure to vinblastine modulates beta 1 integrin expression and in vitro binding to extracellular matrix molecules in a human renal carcinoma cell line.

Solitary stroma-invading tumor cells expressing the ATP-binding cassette transporter P-glycoprotein have been reported to be associated with a significantly higher incidence of vessel invasion and lymph node metastases. In contrast to P-gp-mediated multidrug resistance (MDR) which has become well characterized over the last decade, little is known about further morphological and functional alterations in drug-resistant tumor cells. Binding of malignant cells to components of the extracellular matrix mediated by beta 1 integrins has been suggested to play a substantial role in the metastatic cascade. We studied alterations of beta 1 integrin expression and in vitro adhesiveness to extracellular matrix proteins of the human renal carcinoma line Caki-1 in comparison to the vinblastine resistant sublines Caki-1/V1 and Caki-1/V10 (cultured in the presence of 1 ng/ml and 10 ng/ml vinblastine, respectively). Both VLA-1 and VLA-2 receptors were acquired by the Caki-1/V10 subline, whereas untreated and Caki-1/VI cells lacked surface expression of these antigens. VLA-6 was found to be decreased in the vinblastine-resistant sublines. Attachment of drug-resistant Caki-1/V1 and Caki-1/V10 cells to collagen type I was significantly increased when compared to parental cells (p < or = 0.005). Significant differences in the attachment to type IV collagen were observed between Caki-1/V10 and untreated cells (p < or = 0.045). Both Caki-1/V1 and Caki-1/ V10 cells exhibited increased adhesion to fibronectin when compared to cells of the untreated line (p < or = 0.04). Whether an aberrant expression of beta 1 integrin receptors in resistant cells in combination with altered tumor cell adhesiveness is caused by MDR induction or whether it is an epiphenomenon of cytotoxic stress is unknown. Future studies will be needed to characterize the clinical relevance of MDR-associated changes in tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Biochemotherapy of advanced metastatic renal-cell carcinoma: results of the combination of interleukin-2, alpha-interferon, 5-fluorouracil, vinblastine, and 13-cis-retinoic acid.

We conducted a phase I/II clinical trial evaluating the sequential outpatient combination of S.C. recombinant human interleukin-2 (rIL-2; given at 10 MIU/m2 b.i.d. on days 3-5 weeks 1 and 4 and at 5 MIU/m2 on days 1, 3, and 5 of weeks 2 and 3), s.c. recombinant human alpha-interferon (rIFN-alpha; given at 6 MIU/m2 on day 1 of weeks 1 and 4 and on days 1, 3, and 5 of weeks 2 and 3 and at 9 MIU/m2 on days 1, 3, and 5 of weeks 5-8), i.v. bolus 5-fluorouracil (5-FU; given at 1,000 mg/m2 once weekly during weeks 5-8), and i.v. bolus vinblastine (given at 6 mg/m2 once weekly during weeks 5 and 8) in conjunction with p.o. 13-cis-retinoic acid (13-C-RA; given at 35 mg/m2 daily during weeks 1-8). Therapy was always given in the outpatient setting. Grade 3 constitutional symptoms (malaise, chills, fevers, anorexia) were observed in 4%-8% of treatment cycles and required a 50% reduction in the doses of rIL-2 and rIFN-alpha. None of the patients experienced major 5-FU-related toxicities such as severe diarrhea and/or stomatitis; up to 20% of patients developed vinblastine-associated peripheral polyneuropathy, which was reversible after the cessation of therapy. 13-cis-Retinoic acid produced no significant side effect; no toxic death occurred. Among 24 patients with progressive metastatic disease, there were 4 complete remissions (lung, lymph nodes) and 6 partial remissions (lung, pleura, liver, lymph nodes, and peritoneal carcinosis), for an overall objective response rate of 42% (95% confidence interval, 22%-63%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Body size estimation in eating disorder patients: testing the video distortion method on a life-size screen.

The video distortion method on a life-size screen is a new method for studying eating disordered patients' estimations of their own body width. Testing this method in female patients (53 with anorexia nervosa, 38 with bulimia nervosa) and 36 normal females, yielded high to very high reliability scores (consistency and test-retest stability). A careful analysis of the 'just noticeable difference' showed that a 5% deviation from the undistorted image should be considered as within the range of accuracy. Taking this into account, anorectic patients appear to score below, above, as well as within the normal range. Bulimia nervosa patients are either accurate in their body estimations or overestimate their body width. All control Ss are correct in their estimations. With this method no significant differences were found between the anorectic patients and the controls. Bulimics differ significantly from anorectics and controls on their optative responses (i.e. what they wanted to look like) and their affective responses (i.e. what they felt they looked like).

Adolescent↗

Body size estimation in obese children: a controlled study with the video distortion method.

OBJECTIVE: To investigate the reliability of the video distortion method in obese children and compare their body image with the body perception of non-obese peers. DESIGN: A standardized series of body size estimations: cognitive (what subjects 'think' they look like), affective (what they 'feel' they look like), and optative (what they 'wish' to look like). SUBJECTS: Fourty-one obese children (16 boys and 25 girls, average 12 years old) and 42 age-matched control subjects. MEASUREMENTS: Comparison of percentages of deviation from the accurate body image. RESULTS: The method was shown to be sufficiently reliable in young subjects. Compared with controls, obese children were more accurate in estimating their real body width, but desired to reduce their body size by about 25%. CONCLUSION: The video distortion method can be used as a reliable instrument to assess body perception in obese children.

Adolescent↗

Body size estimation and body dissatisfaction in eating disorder patients and normal controls.

In this study comparing 41 eating disorder patients and 34 female controls, the video distortion technique was used to test the accuracy of body size estimation and to assess the ideal body image. No difference was found in the estimation of actual body sizes, although the accuracy of estimation was quite variable in both bulimics and anorexics. With regard to the ideal body image, significant differences were found: All bulimics and 92.6% of the controls wished to be thinner versus 42.9% of the anorexics (23.8% wished to be larger). Looking at subjective body experience, as measured with a self-report questionnaire (Body Attitudes Test), body dissatisfaction appeared to be negatively correlated with the ideal body image but not with the estimation of actual body sizes.

Adult↗

Detection of clonal T-cell populations in gastrointestinal lymphomas by analysis of cRNA conformational polymorphisms of rearranged T-cell-receptor-gamma genes.

Analysis of complementary RNA molecules of junctional regions of rearranged T-cell-receptor-gamma genes show a pattern of conformational polymorphisms which is specific for an individual lymphocytic clone. In a blinded study we analysed formalin-fixed, paraffin-embedded histological specimens from gastrointestinal lymphomas and control tissues (lymphomas: pleomorphic T-cell 10, anaplastic large cell [Ki1+] 9, centroblastic 5, immunocytoma 1, B-CLL 2, Hodgkin's 2, centroblastic-centrocytic 1, MALT [mucosa associated lymphoid tissue] 1, T-cell acute lymphoblastic leukaemia 1, non-lymphoid or polyclonal lymphoid tissues 5). Junctional regions of rearranged TCR-gamma genes were amplified by the polymerase chain reaction and the products were transcribed into cRNA. Conformational patterns of cRNA molecules were analysed by polyacrylamide gel electrophoresis. 13/20 T-lineage lymphomas and the T-cell acute lymphocytic leukaemia displayed a distinct cRNA band pattern, all B-lineage lymphomas and the non-lymphoid control tissues were negative. Only one case of nasopharyngeal (lymphoepithelial, Schmincke-Regaud) carcinoma showed a faint cRNA banding pattern. This novel and non-radioactive assay allows for the rapid detection and molecular characterization of clonal lymphoid populations in minute histological biopsy specimens.

Base Sequence↗

Acute cholestatic hepatitis and the sudden rise of the pacing threshold 5 weeks after VVI-pacemaker implantation.

The patient we describe developed a cholestatic hepatitis and an unusual threshold elevation of about 425%, coincidently, 5 weeks after pacemaker implantation. Lead dislocation, myocardial infarction or metabolic disorder could be excluded as a reason for the pacemaker complication. Neither a biliary obstruction nor an infection of the liver could be found to explain the liver injury. Most probably, both disorders were caused by propafenone (450 mg day-1), withdrawal of the drug resulted in normalization of elevated enzyme and threshold levels.

Acute Disease↗

Molecular detection and characterization of clonal cell populations in acute lymphocytic leukemia by analysis of conformational polymorphisms of cRNA molecules of rearranged T-cell-receptor-gamma and immunoglobulin heavy-chain genes.

Junctional regions of rearranged T-cell-receptor-gamma (TCR) and immunoglobulin heavy-chain (IgH) genes represent an idiotypic DNA sequence for an individual lymphocytic cell, and any clone or clonal disease developing from this cell. In this study, a novel methodology for detection and characterization of clone specific DNA sequences in patients with acute lymphocytic leukemia (ALL) was developed. Junctional regions of rearranged TCR-gamma IgH genes in specimens of bone marrow aspirates of patients with ALL (precursor-B-ALL ten, T-ALL two, null-ALL one; ALL not classified one), of a patient with lymphoid blast crisis of chronic myeloid leukemia, of a B-cell chronic lymphocytic leukemia, and in DNA from peripheral blood mononuclear cells of ten healthy volunteers were amplified by polymerase chain reaction (PCR). The PCR products were transcribed into complementary RNA (cRNA). Conformational polymorphisms of cRNA molecules were analyzed by non-denaturing polyacrylamide gel electrophoresis. A specific cRNA banding pattern for rearranged TCR-gamma or IgH genes was observed in all patients with lymphocytic leukemia. In contrast, analysis of DNA from healthy volunteers yielded a smear of confluent polymorphisms representing multiple different cRNA molecules. In two patients with precursor-B-ALL, cRNA banding patterns of junctional regions of rearranged TCR-gamma genes were analyzed in sequential bone marrow aspirates. The banding patterns disappeared after chemotherapy and achievement of blast clearance. This novel and rapid molecular assay offers several advantages as compared to Southern blot analyses and previous PCR based methodologies for the detection of clonal lymphocytic populations. With this methodology, studies on the clonal evolution of lymphoproliferative disorders (e.g. the prognostic significance of the emergence of additional clones) can be performed more easily than with any other traditional molecular method.

B-Lymphocytes↗

Conformational polymorphisms of cRNA of T-cell-receptor genes as a clone-specific molecular marker for cutaneous lymphoma.

A novel molecular assay for the detection and characterization of monoclonal lymphoid populations in clinical specimens was developed. The assay is based on the principle that upon non-denaturing polyacrylamide gel electrophoresis RNA molecules separate into several metastable conformational forms. These conformational polymorphisms strictly depend on the nucleotide sequence of the individual molecule. Using DNA from formalin-fixed, paraffin-embedded tissue of patients with mycosis fungoides, highly variable junctional sequences of rearranged T-cell receptor gamma genes were amplified by polymerase chain reaction. Subsequently, the polymerase chain reactions products were transcribed into complementary RNA and analyzed by non-denaturing polyacrylamide gel electrophoresis. In clinical specimens with a monoclonal lymphoid population, a clone-specific pattern of bands was identified representing conformational polymorphisms of cRNA molecules of rearranged T-cell receptor gamma genes of the predominant lymphoid clone. Three biopsies from one patient taken from different sites of the body over 3 years yielded an identical pattern of bands. This methodology provides a novel and rapid tool for the molecular identification and characterization of clonal lymphoid populations in clinical specimens. It is likely to be of special value for studies on the clonal evolution of lymphoid disorders of the skin.

Base Sequence↗

32P-postlabelling studies on the DNA adducts of the food mutagens/carcinogens IQ and PhIP--adduct formation in a chemical system, and by rat and human metabolism.

The DNA adducts of the food mutagens/carcinogens IQ and PhIP were studied by means of 32P-postlabelling techniques. Adducts were generated in vitro and in vivo by three techniques: by photolysis of azido-IQ and azido-PhIP in the presence of dGp, calf-thymus DNA or Salmonella; by administration of IQ and PhIP to rats; and by incubation of cultured COS-1 cells with IQ. These cells expressed the human cytochromes P450 1A1 or P450 1A2 and/or the human N-acetyltransferases NAT1 or NAT2. The data demonstrate that, in the photolytic, rat and human systems, a common IQ metabolite and a common PhIP metabolite are formed together with common sets of IQ adducts and PhIP adducts. The data obtained in the human system show that N-hydroxy-IQ, formed by cytochrome P450, binds poorly to DNA, whereas more efficient binding occurs in the presence of NAT1 and most efficient binding in presence of NAT2. This indicates an O-acetyltransferase activity of human NAT1 and NAT2 and formation of N-acetoxy-IQ as an intermediate and immediate precursor of the ultimate arylnitrenium ion. The effect of the polymorphic NAT2 suggests a critical role for the human acetylation polymorphism in the DNA-binding of IQ in humans and in its genotoxic implications.

Animals↗

Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA-tests in healthy human volunteers.

The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele. In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs. Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted. Overall, the DNA analysis result matched the in vivo phenotype in 97.5% of individuals.

Acetylation↗

Body image assessment in anorexia nervosa patients and university students by means of video distortion: a reliability study.

It is well known that anorexia nervosa is characterized by a disturbed body image. The video distortion method is one of the many methods to systematically study the perceptual aspect of this body image. Using a distorted image of her own appearance, the subject is asked to reconstruct the 'exact' measures of her body and to indicate her ideal image. The reliability of this method has been assessed in a study involving 67 anorexic patients and 105 female university students. Test--retest results within the same session and over a one-week interval were sufficiently constant. Nonetheless, for both anorexics and controls, significant differences were found between estimates with a narrowed (thin) image initially and those with a widened (fat) image initially. Both groups underestimate their body measures and only significantly differ on estimates of their ideal image, with anorexics clearly less underestimating their ideal image than students.

Adult↗