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Biomedical subjects

H Pape

Publications and source records attributed to H Pape.

At least 55 records · Page 3Linked to original sources

Interleukin-6 (IL-6) in adjuvant arthritis of rats and its pharmacological modulation.

The levels of serum interleukin-6 (IL-6) were measured during the course of adjuvant arthritis (FAA) in male Lewis rats. In the course of the disease serum IL-6 levels increase with a clear correlation with morphologic disease signs. Additionally, the FAA-inducing antigen, heat-killed Mycobacterium tuberculosis, was found to be a strong inducer of IL-6 production by spleen cells in vitro. The effects of the anti-rheumatic drugs indometacin, dexamethasone, cyclophosphamide and cyclosporin A (CsA) on IL-6 levels during FAA were determined. Complete normalization of serum IL-6 levels was observed with dexamethasone, cyclophosphamide and CsA whereas indometacin only partly reduced serum IL-6 levels.

Animals↗

Radiotherapy of aggressive fibromatosis.

The long term results of 24 patients treated with postoperative irradiation for aggressive fibromatosis are presented. Tumour sites were the pelvis (8), chest wall (5), shoulder (5), extremities (4) and head and neck (2). Macroscopic complete resection (R1) was performed in 3 cases. 17 patients presented postoperatively with gross disease (R2), 8 of which were recurrent tumours. 4 patients with inoperable disease had biopsies only. Radiation doses ranged from 28 to 64 Gy at a fractionation of 5 x 2 or 4 x 2.5 Gy/week. 4 patients had external irradiation in combination with 192Ir implants, 2 were irradiated with implants alone. In the combined treatment group, external doses ranged from 28 to 52 Gy and additional interstitial doses from 35 to 50 Gy. 192Ir treatment alone was given with 45 and 57 Gy to the contour of the target volume. The 10 year recurrence free survival rate is 75%. A dose response relationship has been established in the dose range of 30-60 Gy revealing an expected 80% persistent tumour control rate at 60 Gy. A dose volume relationship however, could not be derived from our data. Moderate fibrosis without functional impairment developed in 5 patients (21%). These data support a policy of postoperative radiotherapy with 60 Gy in patients with incompletely excised or gross residual tumour following surgery.

Adolescent↗

The prognostic value of DNA content measured by image cytometry in soft tissue sarcomas.

Nuclear DNA content in soft tissue sarcoma was determined by image cytometry using archival, paraffin embedded material. In a retrospective study 138 specimens of 81 patients have been analysed. The ploidy level was correlated to clinical outcome regarding tumor volume and histological grading, the most important prognostic parameters. Ploidy has a significant prognostic value and correlates well with histological grading (p = 0.01). Tumour volume was found to be an independent prognostic factor (p = greater than 0.1) [chi 2 test]. The DNA content of the primary tumour and of multiple local recurrences remained similar.

Adolescent↗

[Attitude towards use of condoms among Norwegian adolescents].

The article discusses the relationship between attitudes towards condoms and the use of condoms among sexually active Norwegian adolescents. The data stem from a random survey of 3,000 Norwegian adolescents aged 17-19. The responsrate was 61.8%. In general, most adolescents were positive towards condoms, and condom users were more positive than non-users. A logistic regression analysis showed that the only statistically significant predictors of condom use were the attitudes 'condoms aren't necessary to me' and 'condoms are uncomfortable'. The results indicate that attitudes towards condoms bear some relation to condom use. But, the use of condoms is also governed by factors other than attitudes.

Adolescent↗

Deficiens, a homeotic gene involved in the control of flower morphogenesis in Antirrhinum majus: the protein shows homology to transcription factors.

Deficiens (defA+) is a homeotic gene involved in the genetic control of Antirrhinum majus flower development. Mutation of this gene (defA-1) causes homeotic transformation of petals into sepals and of stamina into carpels in flowers displaying the 'globifera' phenotype, as shown by cross sections and scanning electronmicroscopy of developing flowers. A cDNA derived from the wild type defA+ gene has been cloned by differential screening of a subtracted 'flower specific' cDNA library. The identity of this cDNA with the defA+ gene product has been confirmed by utilizing the somatic and germinal instability of defA-1 mutants. According to Northern blot analyses the defA+ gene is expressed in flowers but not in leaves, and its expression is nearly constant during all stages of flower development. The 1.1 kb long mRNA has a 681 bp long open reading frame that can code for a putative protein of 227 amino acids (mol. wt 26.2 kd). At its N-terminus the DEF A protein reveals homology to a conserved domain of the regulatory proteins SRF (activating c-fos) in mammals and GRM/PRTF (regulating mating type) in yeast. We discuss the structure and the possible function of the DEF A protein in the control of floral organogenesis.

Amino Acid Sequence↗

The inheritance of the piebald spotting pattern and its variation in Holstein-Friesian cattle and in Landseer-Newfoundland dogs.

The black and white spotting patterns of Landseer dogs are divided into qualitatively recognizable phenotypic classes. Breeding data were obtained from the Swiss Dog Stud Book (SHSB) and from breeders' recent records. A plausible interpretation assumed qualitative inheritance of the generally accepted piebald spotting gene sp1 with at least two modifiers, s2 and s3. The modifier genes are regarded as minor spotting genes and may be responsible for white markings in the related Newfoundland breed which has been cross-bred with Landseers. The proposed scheme of polygenic inheritance can also be applied to the piebald spotting pattern of Holstein-Friesian cattle, using breeding data from literature.

Animals↗

[The therapy of acute radiogenic epitheliolysis with a dressing of hydrocolloids and polymers (Biofilm). A report on clinical experience].

Acute skin lesions following radiotherapy are uncomfortable and unacceptable side effects. They are observed predominantly after high surface doses as in conventional roentgen or electron beam therapy. To accelerate the wound healing we tested a bandage consisting of hydrocolloids and polymers, which is permeable for gas and water. Handling, compatibility and effectiveness of this plaster were tested in this study. According to the RTOG scoring system 19 irradiated fields with grade II to IV lesions were treated. Densitometric measurements of verification films with and without Biofilm showed no energy absorption. The bandage was comfortable for the patients and easy to handle.

Acute Disease↗

Long term results of neutron- and neutron-boost irradiation of soft tissue sarcomas.

The five-year follow-up results of 221 patients treated with neutrons or a neutron-boost at the West German Tumour Centre, Essen, are presented. 94 patients with gross tumour were treated with neutrons alone. 127 patients without gross tumour left behind post surgery were irradiated using a "mixed beam" schedule. The disease-free survival rate at five years is 62.6% for T1-, 71.5% for T2- and 28.7% for T3-tumours (p = 0.016). Significant differences were also found for various grades, i.e. 73.3% for G1-, 47.7% for G2- (p = 0.035) and 22.4% for G3-tumours (p = 0.024). Patients without microscopic tumour residue fared best with a survival rate of 86.6%, followed by patients with microscopic tumour (65.5%; p = 0.042) and patients with gross tumour (25.5%; p = 0.003) left behind. A functional limb was preserved in 86% of the patients with extremity lesions. The local control rate of patients with gross tumour was 76.5% compared with 53% in previous photon series. This finding underlines the potential biological advantage of neutrons in these tumours. Serious side effects ranged from 28% in the patients treated with neutrons for large volumes to 7% in patients treated with a neutron boost.

Evaluation Studies as Topic↗

The role of neutrons in the treatment of soft tissue sarcomas.

Two-hundred twenty-one patients with soft tissue sarcoma were treated from 1978 to 1983. Treatment was nonrandomized and consisted of neutron irradiation in 94 cases with gross tumor. Treatment was nonrandomized and consisted of neutron boost irradiation after photon-irradiation or electron-irradiation in 127 cases with no gross tumor after surgery. Patient distribution according to UICC (1978) criteria was 15, 100, and 106 of T1, T2, and T3 respectively. Distribution by pathologic grade was 54, 107, and 60 for Grade 1, Grade 2, and Grade 3 tumors. Distribution by tumor residuum after surgery was 23 cases without microscopic disease (R0), 104 with microscopic disease (R1), and 94 with gross residuum (R2) or nonoperative disease. Five-year follow-up reveals a significant difference (P = 0.024) in disease-free survival (DFS) for T1 (60%), T2 (71%), and T3 (29%, P = 0.016) tumors. Similarly, there are significant DFS differences among G 1 (74%), G 2 (48%, P = 0.035), and G 3 lesions (22%, P = 0.024). The impact of tumor bulk or residuum on DFS after operation is significant when comparing R0 (87%) and R1 (65%) disease (P = 0.042). The 5-year survival of patients who had gross residuum (R2) after surgery was significantly worse (26%, P = 0.003). Ninety percent of patients failed treatment locally and distally within 2 years. The late morbidity rate was 27% for neutron and 7% for neutron-boost irradiation. In our series and reported photon data, local control rates for tumors 5 to 10 cm with neutrons were 76% and 53%, respectively. Low energy (d(14) + Be) neutrons are considered beneficial in the postoperative treatment of well-differentiated soft tissue sarcomas where gross tumor remains. Neutron-boost irradiation is of potential benefit in the treatment after operation of T2-3, and G 1-2 tumors if there is microscopic residual tumor.

Adult↗

[Combined radiotherapy with cis- or carboplatin in advanced head and neck tumors].

This report reviews the treatment results of 111 patients with stage T3-4, N0-3, M0, biopsy proven squamous cell carcinoma of the oropharynx and oral cavity. All patients were treated by primary irradiation with 1.8 to 2 Gy per day for five days a week up to a target volume dose of 39.6 or 40 Gy. Simultaneously 20 mg/m2 cisplatin was given under hyperhydration and mannitol diuresis on days 1 to 5. In case of partial tumour regression radiotherapy was continued up to 70 Gy with another course of cisplatin. In case of minor response surgery was interposed followed by subsequent irradiation with 30 Gy and a second course of cisplatin. 67% of the patients showed an initial complete tumour involution and 27% a partial response. The five year actuarial survival rate with a minimum follow-up of two years is 47.6%. More than 96% of the long term survivors showed a complete response after the end of treatment. The results demonstrate that concomitant radiation and chemotherapy with cisplatin is a highly effective treatment in advanced head and neck carcinoma with tolerable toxicity. Carboplatin (CBDCA) is a second generation platinum analog and has shown comparable antitumour activity but less nephro- and neurotoxicity than cisplatin in head and neck cancer. In order to determine the feasibility and efficacy of simultaneous application of CBDCA and radiotherapy a phase I-II study is going on. Between September 1987 and March 1988 30 patients with advanced squamous carcinoma of the head and neck (T3-4, N0-3) have entered this trial. Patients were separated into three groups which received 60 mg/m2. 70 mg/m2 and 80 mg/m2 CBDCA from days 1 to 5 and 28 to 32. Radiotherapy was administered up to a target absorbed dose of 70 Gy. 5 X 2 Gy/week in shrinking field technique. The group which received 80 mg/m2 CBDCA reached the myelotoxicity limit so that subsequent patients were treated with 70 mg/m2. Among 30 patients who completed the treatment, 22 showed a complete (CR) and eight a partial remission (PR). Despite the short follow-up period the preliminary results appear to be comparable with those achieved after combined radiotherapy and cis-DDP application without any limitations for patients with renal or cardiovascular disorders.

Antineoplastic Agents↗

[Use of contrast media in MR tomography of soft tissue sarcomas. Follow-up studies after multimodal therapy].

The value of MRI was evaluated retrospectively in 32 patients with clinically confirmed soft tissue sarcomata. The results were compared with the clinical findings and with computed tomographic scans. All patients were examined for recurrent residual tumor, the majority after surgery, radiotherapy and/or chemotherapy. Regardless of the tumor site, MR was superior to CT or at least equivalent. The normal postoperative anatomy was well delineated. Discrimination of recurrent or residual masses from post-treatment fibrosis was good. Bone destruction, especially tumor-induced cortical erosion, was better defined with CT. MRI is an appealing modality for the diagnostic work-up and for the follow-up following treatment of thoracic and abdominal sarcomata in children. The use of Gd-DTPA meant T2-weighted image sequences of the chest and abdomen were unnecessary.

Adolescent↗

[Results of whole lung irradiation and chemotherapy in comparison with partial lung irradiation in metastasizing, undifferentiated soft tissue sarcomas].

The poor prognosis of patients with unresectable pulmonary metastases of soft tissue sarcoma is well known. In order to evaluate the beneficial effect of radiotherapy, we have treated 44 patients with pulmonary metastases of grade 3 soft tissue sarcoma from 1980 to 1986. In 36 patients the treatment volume was restricted to the single metastases up to a dose of 50 to 60 (9 to 10 Gy/week). The survival rate at one year was 18% and at two years 6%. Eight patients were treated with a combined regimen, consisting of cisplatin and ifosfamide with simultaneous whole lung irradiation. Irradiation was performed with 8 or 16 MV photons at a hyperfractionation of 2 x 0.8 Gy/day (8 Gy/week). After a dose of 12 Gy, the single metastases were boosted up to 50 to 60 Gy, with a second course of chemotherapy. In six of eight patients complete remissions were achieved, one patient showed a partial remission. The survival rate at 27 months was 50%. The patients with partial remission died from pulmonary progression at 23 months. One patient died after twelve months from a loco-regional recurrence in the tonsillar fossa without evidence of pulmonary disease. Side effects included alopecia and moderate bone marrow suppression approximately twelve days after each chemotherapy cycle. Pulmonary fibrosis was observed only at the high dose volume without impairment of respiratory function. From these observations the conclusion is drawn that whole lung irradiation simultaneously with cisplatin and ifosfamide chemotherapy provides good palliative results without relevant morbidity in patients with high grade unresectable pulmonary metastases of soft tissue sarcomas.

Adult↗

Studies on the biosynthesis of the alpha-glucosidase inhibitor acarbose: valienamine, a m-C7N unit not derived from the shikimate pathway.

Feeding experiments with Actinoplanes sp. SN223/29 showed that 3-amino-5-hydroxy-[7-13C]benzoic acid is not incorporated into acarbose (I). The valienamine moiety of I is thus not derived in the same way, from the shikimate pathway, as the m-C7N units in the ansamycin, mitomycin and ansamitocin antibiotics. Feeding experiments with [U-13C3]-glycerol followed by analysis of I by multiple quantum NMR spectroscopy support this conclusion and point to formation of the valienamine moiety by cyclization of a heptulose phosphate which arises from a triose phosphate via successive transfer of two 2-carbon fragments by transketolase, as proposed by Pape and co-workers.

Acarbose↗

[Value of radiotherapy in the interdisciplinary therapeutic treatment concept of rectal cancer].

Postoperative radiotherapy reduces the local recurrence rate of rectal carcinoma. However, the recurrence free interval and survival time are not influenced. Postoperative radio- and chemotherapy reduce the local recurrence rate as well and prolongs the recurrence free interval. The survival rate is not significantly improved. Combined pre- and postoperative radiotherapy are presently being evaluated in prospective randomised trials. The actual results demonstrate a reduced local recurrence rate, a prolongation of the recurrence free interval and an improved survival time. Because of the relatively small numbers of patients in the different treatment groups a final evaluation is not yet possible.

Clinical Trials as Topic↗

Biosynthesis of the macrolide antibiotic chlorothricin: basic building blocks.

The biosynthesis of chlorothricin (I), a macrolide antibiotic isolated from Streptomyces antibioticus Tü 99, has been studied by feeding experiments with 14C- and 3H-labeled precursors. Acetate and propionate, but not methionine and mevalonate, were incorporated into the macrocylic aglycone of the antibiotic. Glucose and the various carbon atoms of tyrosine, except the carboxyl carbon, also contributed label to the aglycone. Glucose also seems to be a specific precursor of the 2-deoxyrhamnose moiety, probably via a process involving a hydrogen shift from C-4 to C-6 of the hexose. The substituted 6-methylsalicylic acid moiety seems to be derived from acetate and one O-methyl group provided by methionine; shikimic acid is not incorporated.

Acetates↗