PubMed Health⌕ Search

Biomedical subjects

M Bremer

Publications and source records attributed to M Bremer.

At least 19 recordsLinked to original sources

Reliability and validity of the pain observation scale for young children and the visual analogue scale in children with burns.

The aim of this study was to assess if the pain observation scale for young children (POCIS) and the visual analogue scale (VAS) are reliable and valid instruments to measure procedural and background pain in burned children aged 0-4 years. Burn care nurses (n=73) rated pain from 24 fragments of videotaped children during wound care procedures and during periods of rest using the POCIS and the VAS. Intraclass correlations were used to assess inter-rater and intra-rater reliability for the POCIS and the VAS. Internal consistency for POCIS was assessed by Cronbach's alpha. The POCIS has shown poor to moderate inter-rater reliability, moderate to good intra-rater reliability and an acceptable internal consistency. The VAS turned out to have poor inter-rater reliability and poor to moderate intra-rater reliability. Due to poor results of inter-rater reliability in both scales, construct validation is left undone until more acceptable results are obtained. Factors explaining the results are the large number of raters, the manner they were trained and a lack of variation between pain classes in video fragments. Although not all results were satisfying, an easy to use scale as POCIS has promising qualities and deserves further reliability research.

Adolescent↗

ATM polymorphisms as risk factors for prostate cancer development.

The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17-3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk.

Adult↗

[Spermatocytic seminoma. Report of 2 personal cases and review of the literature].

The spermatocytic seminoma is a distinct testicular neoplasm with a low tendency to metastasize. Two own cases with the diagnosis of a spermatocytic seminoma are presented. A third patient is described, where the initial diagnosis of a spermatocytic seminoma was retrospectively changed to classical seminoma after developing retroperitoneal relapse during surveillance. A literature review revealed distinct histopathological characteristics and a remarkably good prognosis for spermatocytic seminoma. With only one case of relapse confirmed in the literature, in these patients postoperative treatment can safely be omitted in favor of surveillance. In case of spermatocytic seminoma diagnosis should be confirmed by a second pathologist.

Adult↗

Spectrum of ATM gene mutations in a hospital-based series of unselected breast cancer patients.

Blood relatives of patients with the inherited disease ataxia telangiectasia (A-T) have an increased susceptibility for breast cancer. We therefore looked for sequence alterations of the ATM gene in a large hospital-based series of unselected breast cancer patients. The whole ATM coding sequence was analyzed in genomic DNA samples from a core group of 192 consecutive breast cancer cases to define the spectrum of ATM gene mutations. Common sequence alterations were then screened in the whole series of 1000 breast cancer patients and in 500 random individuals. In the core group, 21 distinct sequence alterations were identified throughout the ATM coding region, and 1 common splicing mutation was uncovered in intron 10. Almost half of the breast cancer patients (46%) were heterozygotes for 1 of 16 different amino acid substitutions, and three patients (1.6%) carried a truncating mutation. These data indicate that approximately 1 in 50 German breast cancer patients is heterozygous for an A-T-causing mutation. In our extended series, the most common A-T mutation 1066-6T-->G was disclosed in 7 of 1000 (0.7%) breast cancer patients. Transcript analyses indicated that the loss of exon 11 in the ATM mRNA was the pathogenic consequence of this splicing mutation, which produced a <10% of full-length ATM mRNA and ATM protein in a homozygous A-T patient. We also found an excess of rare missense substitutions in the breast cancer cohort compared with random individuals (7.9% versus 5.3% of alleles; odds ratio = 1.6; P < 0.01). One missense substitution, S707P in exon 15, was two times more frequent in breast cancer patients (odds ratio = 2.4; 95% confidence interval, 1.0-5.8) and five times more frequent in patients with bilateral disease than in random individuals (P < 0.001). We conclude that a large variety of distinct ATM mutations and variants exist among breast cancer patients, some of which can contribute to the etiology and progression of the malignancy. Screening for frequent A-T mutations such as the 1066-6-->G splice site substitution can be effective to prospectively identify A-T heterozygotes in an unselected cancer patient population.

Adenocarcinoma↗

Mutations of the BRCA1 and BRCA2 genes in patients with bilateral breast cancer.

Mutations of the BRCA1 or BRCA2 genes have been shown to strongly predispose towards the development of contralateral breast cancer in patients from large multi-case families. In order to test the hypothesis that BRCA1 and BRCA2 mutations are more frequent in patients with bilateral breast cancer, we have investigated a hospital-based series of 75 consecutive patients with bilateral breast cancer and a comparison group of 75 patients with unilateral breast cancer, pairwise matched by age and family history, for mutations in the BRCA1 and BRCA2 genes. Five frameshift deletions (517delGT in BRCA1; 4772delA, 5946delCT, 6174delT and 8138del5 in BRCA2) were identified in patients with bilateral disease. No further mutations, apart from polymorphisms and 3 rare unclassified variants, were found after scanning the whole BRCA1 and BRCA2 coding sequence. Three pathogenic BRCA1 mutations (Cys61Gly, 3814del5, 5382insC) were identified in the group of patients with unilateral breast cancer. The frequencies of common BRCA1 and BRCA2 missense variants were not different between the 2 groups. In summary, we did not find a significantly increased prevalence of BRCA1 and BRCA2 mutations in a hospital-based cohort of German patients with bilateral breast cancer. We conclude that bilaterality of breast cancer on its own is not strongly associated with BRCA1 and BRCA2 mutations when adjusted for age and family history. The high frequency of bilateral disease in multi-case breast cancer families may be due to a familial aggregation of additional susceptibility factors modifying the penetrance of BRCA1 and BRCA2 mutations.

Adult↗

Nematic liquid crystals with a tetrafluoroethylene bridge in the mesogenic core structure.

A dramatic increase of the clearing temperatures of liquid crystals based on bis(cyclohexyl)ethane 1 by 50 to 70 K can be achieved by the perfluorination of the central ethylene link. Conformational analysis indicates that this effect is due to the increased rigidity of the mesogenic core structure and to the suppression of conformers with a bent shape. Materials based on bis(cylohexyl)tetrafluoroethane 2 might play a crucial role as materials for the next generation of active matrix LCDs with reduced power consumption.

Journal Article↗

[Bilateral breast carcinoma and local recurrence: prevalence of BRCA-1 and BRCA-2 gene mutations in an unselected patient sample].

BACKGROUND: Mutations of the BRCA 1/BRCA 2 genes strongly predispose towards the development of contralateral breast cancer. We therefore investigated a hospital-based series of patients with bilateral breast cancer and a comparison group of patients with unilateral breast cancer, pairwise matched by age and family history, for mutations of the BRCA 1/BRCA 2 genes. PATIENTS AND METHODS: Between 1995 and 2000 genomic DNA from blood samples of 75 patients with bilateral breast cancer, who received postoperative radiotherapy, was analyzed for mutations of all coding regions and flanking intron sequences of the BRCA 1/BRCA 2 genes by single strand conformation polymorphism analysis (SSCP) and sequencing of aberrant findings. The results were compared to 75 unilateral breast cancer patients who were screened for common mutations in the BRCA 1 and BRCA 2 genes. Treatment results of patients with bilateral disease were analyzed with regard to a possible carriership of a BRCA 1/BRCA 2 gene mutation. RESULTS: Five distinct frameshift deletions (one in BRCA 1, four in BRCA 2) were identified in six patients with bilateral breast cancer. Three of six carriers developed local relapse, whereas this was the case in only nine of 69 non-carriers. After radiotherapy local relapse occurred in five patients (five of 126 irradiated breasts or chest walls). Three of these patients (60%) were carriers of a pathogenic BRCA 1/BRCA 2 mutation. In the comparison group of patients with unilateral breast cancer three pathogenic BRCA 1 mutations were identified. CONCLUSIONS: We failed to confirm an increased prevalence of BRCA 1/BRCA 2 mutations in our hospital-based series of patients with bilateral breast cancer. However, local relapse, especially when occurring after radiotherapy, may be predictive for an underlying pathogenic BRCA 1 and BRCA 2 gene mutation in patients with bilateral breast cancer.

Adult↗

Spondylodiscitis in patients with spinal cord compression: a possible pitfall in radiation oncology.

PURPOSE: In patients presented for spinal irradiation it may be difficult to distinguish between malignant and benign lesions if only plain X-rays and computed tomography (CT)-scans are available. Spinal magnetic resonance imaging (MRI) can be of great diagnostic value. METHODS: From 11/1995 to 05/2000 447 patients were presented for spinal irradiation, 264 beyond regular operating hours. At presentation no spinal MRI was available in 170/447 and 132/264 patients. RESULTS: After spinal MRI, diagnosis was changed from vertebral metastases to spondylodiscitis in 10/170 and 8/132 patients. Six of these patients were already known as cancer patients. CONCLUSION: In patients presented for spinal irradiation spondylodiscitis is not very uncommon. If there is any doubt about metastatic disease as the cause for spinal cord compression a spinal MRI has to be demanded, even beyond regular operating hours.

Aged↗

Local anesthetics attenuate lysophosphatidic acid-induced priming in human neutrophils.

UNLABELLED: Lysophosphatidic acid (LPA) is an intercellular phospholipid mediator with a variety of actions that suggest a role in stimulating inflammatory responses. We therefore studied its actions on neutrophil (PMN) motility and respiratory burst. Because local anesthetics (LA) inhibit LPA signaling and attenuate PMN responses, we also investigated the effects of LA on these actions. Chemotaxis of human PMNs under agarose toward LPA (10(-10)-10(-3) M) was studied, with and without 1 h prior incubation in lidocaine (10(-9)-10(-4) M). Priming as well as activating effects of LPA on PMNs were measured using a cytochrome-c assay of superoxide anion (O2-) production. PMNs were incubated with lidocaine, tetracaine, or S-(-) ropivacaine (all at 10(-6)-10(-4) M) for 10 min or 1 h to assess interference with LPA signaling. LPA demonstrated chemoattractive effects towards human PMNs; this effect was concentration-dependently attenuated by lidocaine. LPA alone did not activate PMNs. However, it acted as a priming agent. LA in clinically relevant concentrations decreased (O2-) production induced by LPA/N-formylmethionine-leucyl-phenylanaline. LPA acts as a chemoattractant and priming agent; however, it does not activate PMNs. LA, in clinically relevant concentrations, attenuate chemotactic and metabolic responses as a result of LPA. These results may explain the antiinflammatory effect of local anesthestics. IMPLICATIONS: Lysophosphatidic acid (LPA) influences two functions of human neutrophils, migration and metabolic activity. It acted as a chemoattractant and a priming-but not activating-agent. Responses to LPA were attenuated by local anesthetics in clinically relevant concentrations.

Anesthetics, Local↗

Time of developing motor deficits before radiotherapy as a new and relevant prognostic factor in metastatic spinal cord compression: final results of a retrospective analysis.

The aim of this retrospective analysis was to determine the prognostic value of the time of developing motor deficits before radiotherapy (RT) and to confirm our preliminary results by achieving statistical significance. Of 529 patients receiving spinal irradiation (1994-1998) 131 fulfilled the selection criteria. Three groups were formed according to time of developing motor deficits: 1-7 days (n = 51), 8-14 days (40), >14 days (40). Motor function was graded before, 2 weeks and 3 months after RT. After 2 weeks, patients developing motor deficits for >14 days showed improvement more often than patients of the other groups (65 versus 32.5 and 4%, p < 0.001). After 3 months results were comparable (p < 0.001). A slower development of motor deficits predicts a better functional outcome. Time of developing motor deficits before RT is a relevant prognostic factor in metastatic spinal cord compression.

Adult↗

Prognostic significance of the time of developing motor deficits before radiation therapy in metastatic spinal cord compression: one-year results of a prospective trial.

PURPOSE: To investigate prospectively the prognostic value of the time of developing motor deficits before radiation therapy (RT) for post-treatment functional outcome in metastatic spinal cord compression. METHODS AND MATERIALS: From November 1998 until October 1999, 57 patients were included. Two subgroups were formed according to the time of developing motor deficits before RT: 1-14 days (n = 29) and > 14 days (n = 28). Therapeutic effect on motor function was evaluated by an 8-point scale directly, 6, 12, and 24 weeks after RT. Patients with rapid deterioration of motor function within 48 h before RT (n = 14) were evaluated separately. RESULTS: Directly after RT, 26/28 patients (93%) of the group developing motor deficits > 14 days showed improvement of motor function, in comparison to 3/29 patients (10%) of the group 1-14 days (p < 0.001). Deterioration rates were 0% (> 14 days) and 45% (1-14 days). In patients with rapid deterioration of motor function within 48 h before RT, prognosis was poor (improvement 0%, no change 43%, deterioration 57%). Results were comparable 6, 12, and 24 weeks after RT. CONCLUSION: A slower development of motor deficits before RT predicts a better post-treatment functional outcome. In patients with rapid deterioration of motor function within 48 h before RT, prognosis was extraordinarily poor. These results support the findings of our preceding retrospective analysis.

Adult↗

Which electron count rules are needed for four-center three-dimensional aromaticity?

A series of charged and neutral four-center n-electron (4c-ne, n = 1-4) molecules based on the adamantane framework, but which include combinations of boron, nitrogen, and phosphorus atoms at bridgehead positions, were studied computationally at the B3LYP/6-31G* level of density functional theory (DFT). The three-dimensional aromaticity, observed earlier for the 1,3,5,7-bisdehydroadamantane dication (1), is found to be general for 4c-2e electron systems. The degree of electron delocalization, evaluated by energetic, geometric, and various magnetic criteria, is quite independent of the molecular symmetry (point groups vary from Td to Cs), the degeneracy of the orbitals, the molecular charges, and the nature of the atoms participating in the delocalized bonding. Although the multiple positive (e.g., in 1 and some of the heteroatom systems) and multiple negative charges are strongly repulsive, the rigid adamantane frameworks help hold the bridgehead atoms within bonding distances with the fewer available electrons. The corresponding 4c-1e doublets are approximately half as aromatic as the 4c-2e singlets based on the same criteria. However, the three-electron systems may either adopt distorted but still four-center delocalized structures, or alternative 3c-2e two-dimensional arrangements in which the fourth bridgehead atom is more distant. There is no need to derive special rules for each point group for 4c-ne systems. Although the three-dimensional stabilization is computed to be quite appreciable, ranging between 10 and 50 kcalmol(-1), this delocalization energy is generally not sufficient to overcome distortion due to strain in higher homologues of 1 and in analogous noncage systems. Among the various 4c-2e homoadamantanedehydro dications studied, only the 1,8-dehydrohomoadamandiyl-3,6-dication forms a three-dimensional aromatic system.

Journal Article↗

Palliative radiotherapy of malignant melanoma with reactor fission neutron therapy (RENT): a prospective study.

To study the efficacy and safety of relatively low-dosed reactor fission neutron therapy (RENT) at the research reactor of the Technical University Munich, we treated 33 superficial lesions of 20 patients with advanced malignant melanoma by neutron beam alone (n = 22), mixed neutron/electron beam (n = 5), or by neutron beam after incomplete surgery (n = 6). Median tumor volume was 17.0 cm3. Median dose for neutron beam alone was 8.0 Gy and for mixed beam 3.0 Gy n + 45.3 Gy e-. Local tumor response, local control time, survival and treatment related toxicity were followed prospectively over a time period of 52 months. Overall response rate (CR;PR) after neutron beam alone and mixed beam therapy was 64% (CR: 36%) and 100% (CR: 60%), respectively. Observed differences between complete (CR) and incomplete (PR, NC) responding lesions were as follows: median tumor volume: 2.0 vs. 51.5 cm3, local control time: 13.3 vs. 3.7 months, median survival: 19.8 vs. 9.0 months. No severe acute or late sequelae could be observed. In conclusion, low-dosed RENT is an effective and well tolerated palliative treatment of superficial malignant melanoma utilizing the biologic advantage of diminished cellular repair capacity. Because melanoma lesions of small size (< or = 6 cm3) tend to respond completely, neutron beam should be performed at an early stage.

Adult↗

New drugs for BNCT: an experimental approach.

New kinds of boron-containing drugs were developed and tested in several murine tumor models. The boron-containing ether lipid B-Et-11-OMe was injected in mammary carcinoma (AT17) and osteosarcoma (OTS-64) bearing mice. Furthermore boron-substituted ferrocenium derivatives were tested. Two were excessively toxic; the third could be investigated. Boron accumulation and time-dependent biodistribution were determined using alpha-particle sensitive films and inductively coupled plasma-atomic emission pectrometry (ICP-AES) and -mass spectrometry (ICP-MS) of tumors, organs and tissues. Additionally, a new method of boron detection by NMR is in preparation.

Animals↗

Metastatic spinal cord compression. Influence of time between onset of motoric deficits and start of irradiation on therapeutic effect.

BACKGROUND: In a retrospective analysis we investigated the prognostic significance of the interval between first appearance of motoric deficits and the beginning of radiation therapy (RT) with regard to posttreatment motoric function. MATERIAL AND METHODS: Data of more than 400 consecutive patients being irradiated at our department between 1994 and 1997 because of vertebral metastases were reviewed. Ninety-six patients fulfilled selection criteria including motoric deficits, no preceding surgical or radiotherapeutic treatment of the spine, minimum total dose of 24 Gy referred to spinal cord, and additional treatment with dexamethasone. Two subgroups with a similar number of patients for better comparability were formed according to the time of developing motoric deficits: 1 to 13 days (49 patients) and > or = 14 days (47 patients). Effect of irradiation on motoric function was evaluated 2 weeks and about 3 months after radiotherapy. Patients with severe deterioration of motoric function within 48 hours before radiation therapy (31 patients) were looked at separately. RESULTS: Two weeks after radiotherapy 42/47 patients (89%) developing motoric deficits > or = 14 days showed improvement of motoric function in comparison to 6/49 patients (12%) of the other group. Deterioration occurred in 1/47 patients (2%) of the first and in 24/49 patients (49%) of the latter group. In case of severe deterioration of motoric function within 48 hours before radiation therapy only 2/31 patients (6%) showed improvement, but 20/31 (65%) deterioration. About 3 months after radiotherapy comparable results were observed. Median survival time was 4 months. CONCLUSION: A slower development of motoric deficits before beginning of radiotherapy means a better therapeutic effect and a more favorable functional outcome after treatment. The prognosis is extraordinarily poor if severe deterioration of motoric function occurs within 48 hours before radiotherapy.

Humans↗

Effectiveness of hypofractionated radiotherapy in painful bone metastases. Two prospective studies with 1 x 4 Gy and 4 x 4 Gy.

BACKGROUND: Although effectiveness of fractionated radiotherapy for painful bone metastases is well documented, there are unanswered questions regarding the adequacy of low-dose short radiation schedules for long-term pain control which give maximum benefit in patients with a short life expectancy. PATIENTS AND METHODS: Two consecutive non-randomized prospective follow-up studies were performed at a single institution to analyze pain response and duration of response in patients with a variety of primary tumors. Included were only patients with symptomatic nonvertebral bone metastases and without impending pathologic fracture. Forty-five patients received 1 x 4 Gy to 50 different sites (group I) while 86 patients received 4 x 4 Gy to 96 sites (group II). Pain relief to irradiation was evaluated according to patient interviews using a 4-point categorical scale. Follow-up was performed 7 and 90 days after radiotherapy. RESULTS: Pain relief after 4 x 4 Gy was significantly superior to 1 x 4 Gy with pain control rates being 86.5% vs 48% at day 7 (after end of treatment) and 80% vs 55% at day 90, respectively. A subgroup analysis of patients treated with 4 x 4 Gy demonstrated a more favorable outcome for breast cancer patients in comparison to patients with other primaries concerning pain relief (96% vs 81%), pain control after 90 days (93% vs 72%), median time to pain progression (9 vs 3 months), and median overall survival (14 vs 5.5 months). CONCLUSIONS: In this study 4 x 4 Gy proved to be clearly superior to 1 x 4 Gy in relieving pain from symptomatic nonvertebral bone metastases without impending pathologic fracture. Even if radiotherapy with 1 single fraction seems to be applicable in specific cases doses higher than 4 Gy should be chosen. In breast cancer patients pain control seems to be better compared to other primaries.

Aged↗