Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

At least 37 records · Page 2Linked to original sources

PubMed2003

[The time-course of action of rapacuronium and mivacurium after early reversal following equally lasting relaxation].

This study was designed to compare the time course of action and the safety profile of Rapacuronium and Mivacurium in day case dental surgery. After Ethics Committee approval 61 healthy adult patients, scheduled for dental day case surgery, were randomised in an assessor-blinded manner to receive either 1.5 mg/kg Rapacuronium with and without 0.05 neostigmine 5 min later (19 patients each) or a total of 0.25 mg/kg Mivacurium (n = 16). Anaesthesia was induced using Propofol 2 - 5.1 mg/kg and Remifentanil 24 - 73 mcg/kg/h and maintained with Desflurane in N2O/O2 (2/1). Endotracheal intubation was performed when maximum blockade was achieved and scored by a blinded intubator. Neuromuscular block was monitored using the train-of-four response to supramaximal stimuli at the ulnar nerve every 15 seconds using acceleromyography (TOF Watch SX). Onset time, clinical duration (reappearance of the third twitch of a TOF-stimulation) and recovery to T4/T1 > 0.9 were recorded. Speed of recovery was evaluated by the time difference between reappearance of the third twitch and T4/T1 > 0.9. The intubating conditions at the time of maximum block revealed no statistically significant differences between the three groups. Changes in blood pressure, heart rate and airway pressure were not significant. Onset time in subjects who received Rapacuronium (99 +/- 29 s) was faster compared to the onset time in those who received Mivacurium (157 +/- 36 s). Also clinical duration was significantly shorter following Rapacuronium without reversal (12 +/- 4 min) as well as with reversal (9 +/- 1 min) compared with Mivacurium (21 +/- 5 min)). Patients treated with Rapacuronium and reversal recovered faster (14 +/- 8 min)) compared to the other two groups (Mivacurium: 20 +/- 6 min, Rapacuronium without reversal: 31 +/- 9 min). The fraction of clinical duration of the total duration was highest following Mivacurium (51 %) when compared with Rapacuronium/Neostigmine (43 %) and Rapacuronium (28 %).

Adolescent↗

PubMed2003

Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans.

Chromosome aberrations and sister chromatid exchanges (SCEs) were determined in standard peripheral lymphocyte metaphase preparations of 13 British Gulf War veterans, two veterans of the recent war in the Balkans and one veteran of both wars. All 16 volunteers suspect exposures to depleted uranium (DU) while deployed at the two different theatres of war in 1990 and later on. The Bremen laboratory control served as a reference in this study. Compared with this control there was a statistically significant increase in the frequency of dicentric chromosomes (dic) and centric ring chromosomes (cR) in the veterans' group. indicating a previous exposure to ionising radiation. The statistically significant overdispersion of die and cR indicates non-uniform irradiation as would be expected after non-uniform exposure and/or exposure to radiation with a high linear energy transfer (LET). The frequency of SCEs was decreased when compared with the laboratory control.

Adult↗

PubMed2002

[Biological markers in epidemiology: concepts, applications, perspectives (part I)].

The inclusion of biomarkers in epidemiological research provides new possibilities for exposure assessment and the study of early structural or functional changes and pre-clinical stages of diseases. At the same time issues of validity, reliability, and quality control as well as logistics require special attention. Usually epidemiological studies become more expensive with regard to time and cost. Interdisciplinary collaboration between epidemiology, basic research, and laboratory research is crucial. A prerequisite for this collaboration are agreements on definitions, methods and procedures. The definition of "biomarker" and a description of previous uses of biomarkers in epidemiological studies are presented in the first part of this paper. The second part addresses genetic markers and markers of individual sensitivity and susceptibility. We will end with a discussion about the possible future of biomarkers in epidemiology.

Biomarkers↗

PubMed2002

[Biological Markers in Epidemiology: Concepts, applications, Perspectives (Part II)].

The first part of this paper outlined terms and definitions in the context of the application of biological markers in epidemiological studies. Cardiovascular epidemiology served as an example for their historical development. The second part focusses on DNA-based biomarkers, practical and methodological dimensions of the use of biomarkers in analytic epidemiological studies as well as requirements in respect of validity and quality assurance. Most genetic polymorphisms have no impact on health. However, some can be used as biomarkers for individual sensitvity to exposures and susceptibility for specific diseases. The Human Genome Project has brought about a quantum leap in the development of genetic markers. The practical implications cannot presently be assessed with certainty. However, present and future research programmes of gene-environment interactions depend on "traditional" epidemiological study designs, methods, and concepts. Ethical principles and data protection requirements apply equally to genetic and molecular epidemiology as do the "Guidelines for Good Epidemiological Practice".

Biomarkers↗

PubMed2002

High resolution emission spectra of TL materials.

High resolution emission spectra of several TL materials, that are commonly used in dosimetry, were measured using a low cost fibre optic spectrometer containing a 2048 pixel CCD array. The spectra were taken from 177 to 890 nm with a wavelength resolution of 1.3 nm. This allowed for line width discrimination and the resolution of transitions that have not been seen so far. For rare earth doped materials like CaF2:Tm (TLD-300) and CaF2:Dy (TLD-200) the spectral lines were compared to the energy levels measured by Dieke and Crosswhite leading to the identification of most of the transition lines.

Aluminum Oxide↗

PubMed2002

Estimation of x ray overexposure in a childhood leukaemia cluster by means of chromosome aberration analysis.

Only multiple X ray diagnostics could be identified as a common risk factor in a leukaemia cluster that appeared between 1985-1989 in the municipality of Sittensen in northern Germany. In order to judge if the effect could be explained by irradiation dose, estimates were done in two of the leukaemia cases and seven former patients of a practice where some of the leukaemia cases had been treated for orthopaedic reasons. The methods used for the reconstruction of doses were physical simulation and biological dosimetry by dicentric chromosomes in peripheral lymphocytes. Compared to the Bremen laboratory control the mean frequency of dicentric chromosomes in the lymphocytes of the seven volunteers was significantly elevated. An overexposure of about 12-fold could be derived compared to state of the art X raying. At least two cases of the leukaemia cluster in Sittensen can therefore be correlated to an overexposure by diagnostic X rays.

Acute Disease↗

PubMed2001

Specific secretion of gel-forming mucins and TFF peptides in HT-29 cells of mucin-secreting phenotype.

Trefoil factor family (TFF) peptides are typical secretory products of mucin-producing cells, e.g. of the gastrointestinal tract. Here, the expression and secretion of mucins and TFF peptides was studied in the HT-29 cell line throughout cellular growth and differentiation in relation to a mucin-secreting (HT-29 MTX) or an enterocyte-like (HT-29 G(-)) phenotype. mRNAs of several MUC and TFF genes were expressed in both cell subpopulations. However, for most MUC and TFF genes, the expression appeared strongly induced with the differentiation into the mucin-secreting phenotype. On the other hand, TFF2 was specifically expressed in the mucin-secreting HT-29 MTX cells. The differentiation of HT-29 MTX cells into the mucin-secreting phenotype was characterised by secretion of the gel-forming mucins MUC2, MUC5AC, and MUC5B, however, according to a different pattern in the course of differentiation. A significant amount of TFF1 and TFF3 was secreted after differentiation, also according to a different pattern, whereas TFF2 was only faintly detected. Secretagogues, known to induce the secretion of mucus, increased the secretion of all three TFF peptides. In contrast, neither a secretory mucin nor a TFF peptide was found in the culture medium of HT-29 G(-) cells. Overlay assays indicated that HT-29 MTX mucins bound to secretory peptides of HT-29 MTX cells with relative molecular mass similar to TFF peptides. TFF1 and TFF3 were specifically localised in the mucus layer of HT-29 MTX cells by confocal microscopy. Finally, the secretion of TFF peptides and mucins appears as a co-ordinated process which only occurs after differentiation into goblet cell-like phenotype.

Cell Differentiation↗

PubMed2001

The novel ependymin related gene UCC1 is highly expressed in colorectal tumor cells.

Normal cells differ from malignant tumor cells in the transcription levels of many different genes. Two colorectal tumor cell lines were compared with a normal colorectal cell line by differential display reverse transcription PCR to screen for tumor cell specific differentially transcribed genes. By this strategy the upregulation of a novel gene was detected designated as 'upregulated in colorectal cancer gene-1' (UCC1). The UCC1 gene transcript level is increased in cultured tumor cells and in two out of three analyzed colorectal tumor tissue specimens compared to normal cultured cells and to corresponding normal tissue samples. Remarkably, the UCC1 protein shows significant sequence similarity to the highly divergent piscine glycoproteins termed ependymins which are synthesized by leptomeningeal fibroblasts and secreted into the cerebrospinal fluid.

Amino Acid Sequence↗

PubMed2001

Irradiation of histiocytosis X confined to the oral mucosa.

BACKGROUND: Histiocytosis X is a rare granulomatous disease and it is still under debate as to whether this disease has to be counted among malignant tumors or benign immunologic lesions. The typical localization is confined to the bone. In rare cases histiocytosis X may be localized in the oropharyngeal mucosa. PATIENTS AND METHODS: We report about a case of a 75-year-old woman presenting with histiocytosis X lesions solely located in the oral cavity. A total dose of 19.5 Gy was administered without any side effects. RESULTS: Two weeks after completion of irradiation a rapid regression of mucosal ulcerations and improvement of symptoms occurred. In a follow-up of 24 months the patient is still in complete remission observed. CONCLUSION: Review of the literature revealed only casuistic reports about solitary lesions of histiocytosis X without bone involvement in the adulthood. External beam radiotherapy with total doses between 10 and 20 Gy seems to be effective for local control of this disease.

Aged↗

PubMed2001

[TFF peptides. New mucus-associated secretory products of the conjunctiva].

The molecular architecture of the human ocular mucus is not yet completely understood. Recently, TFF peptides (formerly known as trefoil factors or P-domain peptides) could be identified as new constituents of this delicate mucus. Members of the TFF-peptide family are typical secretory products of mucous epithelia and three are known in humans and designated as TFF1, TFF2 and TFF3. They enhance cell migratory processes (motogenic effect), they show anti-apoptotic effects and are inflammatory modulators Both TFF1 and TFF3 expression could be monitored by the reverse transcription-polymerase chain reaction (RT-PCR) in the human conjunctiva; in contrast, TFF2 transcripts were not detectable. Using immunohistochemistry, TFF1 and TFF3 peptides were found in varying concentrations solely in secretory vesicles of conjunctival goblet cells. This localisation matches precisely that of the secretory mucin MUC5AC. Thus, conjunctival TFF1 and TFF3 have to be considered as typical mucin-associated peptides probably modulating the rheological properties of the ocular mucus and the tear fluid. Future investigations are in progress to elucidate the role of TFF-peptides during pathological conditions of the eye as well as their diagnostic and therapeutic potential.

Conjunctiva↗

PubMed2001

Loss of heterozygosity at 11p15 and p53 alterations in malignant gliomas.

PURPOSE: Malignant gliomas are the most frequent primary brain tumors. Recent studies defined several genetic markers, which might characterize molecular-biological subsets of glioblastomas with prognostic implications. In the later steps of tumor-progression, deletions on chromosome 11p15 and mutations of the tumor suppressor gene p53 were determined for different malignancies. To elucidate the involvement of 11p15 deletions in the tumorigenesis of malignant gliomas, we analyzed a series of 50 glioblastomas for loss of heterozygosity (LOH). METHODS: Paired tissue and blood samples from 50 patients with glioblastoma multiforme were included. Microsatellite markers located on 11p15.1-11p15.5 were used for LOH analysis. Additionally, mutation analysis of the tumor suppressor gene p53 was performed, which might correlate with favorable survival in glioblastomas. RESULTS: The region 11p15.4-5 was deleted heterozygously in 28% of cases representing 15 cM. Twenty-six glioblastomas did not show allelic loss for any locus. Our data revealed close association of LOH 11p15 with p53 mutations, and survival analysis showed a trend indicating better prognosis in glioblastomas characterized by LOH 11p15. CONCLUSION: In the tumorigenesis of malignant gliomas, p53 mutations and 11p15 deletions seem to indicate a genetic subset of tumors with favorable prognostic value.

Brain Neoplasms↗

PubMed2001

Synthesis and localization of the mucin-associated TFF-peptides in the human uterus.

TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and are thought to influence the rheological properties of mucous gels. Here, the localization of these peptides in the human uterus was investigated. An analysis of TFF-peptides mRNA by the polymerase chain reaction revealed TFF3 mainly in the endocervix and smaller amounts in the endometrium. TFF1 and TFF2 mRNA was detectable occasionally in the endocervix and very rarely in the endometrium. Western blot analysis detected only TFF3 in tissue extracts of the endocervix and as a constituent of human cervical mucus. Immunofluorescence localized TFF3 in the surface epithelium of the endocervix and in gland-like structures of the cervical epithelium.

Blotting, Western↗

PubMed2001

Ultrastructural co-localization of TFF3-peptide and oxytocin in the neural lobe of the porcine pituitary.

TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory products of many mucous epithelial cells. TFF3 is also synthesized in oxytocinergic neurons in the paraventricular and supraoptic nuclei of the human hypothalamus. Here, TFF3 and oxytocin are shown to be co-localized within the same secretory vesicles in the neural (posterior) lobe of the procine pituitary by means of immunoelectron microscopy. Relatively large amounts of TFF3, but not TFF1 and TFF2, are present in the neural lobe of the porcine pituitary, where it is probably released into the bloodstream.

Animals↗

PubMed2001

[Treatment of cancer pain with opioid analgesics in outpatients 1993 and 1996. Results of a population based evaluation].

UNLABELLED: Pertinent guidelines recommend opioid-type analgesics for management of severe pain. However, in the past, opioids were prescribed for only a minority of these patients. In this representative study we examined the prevalence of cancer patients with and without opioid prescription in their final year of life in 1993 and 1996 in Bremen, Northern Germany. METHODS: Complete four-months-samples of patients with cancer in Bremen were abstracted from the death certificates of 1993 and 1996. For the final years of these patients information on opioid-type prescriptions were recorded using the duplicates kept in the pharmacies. To assure data privacy the matching was performed in a cryptographic computer program installed on laptop computers. RESULTS: A total 489 (453) prescriptions could be matched to 435 (421) deceased patients with cancer in 1993 (1996) in 92% of all pharmacies in Bremen. In 1996, 20% of the patients with cancer received at least one prescription, including 14.5% who received opioids for eight weeks or longer. Average morphine-equivalent for each treated patient was 3712 mg (median=462 mg). There was no trend in prescription prevalence and the proportion of prescribing medical practices. The proportion of patients who received opioids for longer periods increased 4%. However, among the treated patients the average morphine-equivalent increased 23%. CONCLUSION: The prescription prevalence of opioids remains low among cancer patients in their final year of life. However, our study provides some evidence for positive developments with respect to prescription times and dosage between 1993 and 1996. These changes are likely due to a limited subgroup of practioners.

Ambulatory Care↗

PubMed2001

[Epidemiology, social medicine, environmental medicine--a plea for a difficult but necessary integration].

The origins of environmental medicine date back more than 2000 years. The increasing incidence of environmental disease together with successful research into their etiology and pathogenesis have caused an impetus for this discipline in quantitative terms. A growing interest of patients, but also of politicians and parts of the industry in actual or suspected environmental risk factors for health have given rise to controversies--rendering the development of a rational, quality-oriented environmental medicine difficult, if not impossible. Given these controversies surrounding environmental health issues formal demarcations between the traditional disciplines (environmental) epidemiology, social medicine, occupational medicine, and environmental medicine become obsolete. Instead, a common agenda with respect to research, quality assurance, risk communication, and prevention as well as patient counselling and policy advising calls for a conceptual and institutional integration of these disciplines.

Environmental Medicine↗

PubMed2001

[Breast cancer mortality in women in the Schleswig-Holstein district 1981 to 1995].

The present descriptive study evaluates breast cancer mortality among women in the northernmost German Federal State of Schleswig-Holstein over the period from 1981 to 1995 based on data provided by the Schleswig-Holstein State Office for Statistics. Starting from the results of the second Cancer Atlas for the Federal Republic of Germany [11], covering the period 1976-1980, breast cancer mortality rates rose sharply until the beginning of our investigation. A moderate rise in breast-cancer mortality in Schleswig-Holstein continued until the third period under investigation (1987-1989), while after that time breast cancer mortality decreased again towards the end of the investigation period. In Schleswig-Holstein as a whole, the mortality rate increased by approximately 12% during the last 20 years. When reviewing age-specific breast-cancer mortality for each rural district ('Kreis') or, respectively, for each self-administrative town (kreisfreie Stadt), different patterns were observed, particularly among younger women. In the 40- to 44-year and 45- to 49-year age group a rise in breast cancer mortality was observed in several, but not all districts. Mortality patterns do not tend to be representative for breast cancer incidence because mortality reflects only a small proportion of the women actually suffering from breast cancer. The standardised incidence of breast cancer in Germany--calculated on the basis of data provided by the Saarland cancer registry--is currently over 60/100,000 and is thus 2-3 times the mortality rate. However, presently it is not possible to evaluate the breast cancer incidence (Schleswig-Holstein) because the first population-based cancer registration was initiated only in 1999. In contrast to other German Federal States, notification of all cancer cases is compulsory in Schleswig-Holstein. A valid analysis of breast cancer incidence should be possible in 5-10 years conditional on a registration rate of at least 90%. Further investigations into the causes of breast cancer should be carried out to test specific hypotheses on exposure to risk factors, including nutrition and life style to clarify the regional differences observed in this study.

Adult↗

PubMed2001

"Host factors"--evolution of concepts of individual sensitivity and susceptibility.

The detection of a rapidly increasing number of genetic polymorphisms in xenogen-metabolizing enzymes, of hereditary as well as acquired individual differences in DNA repair, and of the close associations between central nervous structures, the endocrine, and the immune system provides a challenge to develop an evidence-based, comprehensive model of susceptibility. Reviewing the evolution of respective approaches from 400 B.C. until today, this article proposes a conceptional framework that integrates the diverse, and sometimes puzzling contributions from all different fields of life science.

Biological Evolution↗

PubMed2001

An application of the challenge assay in boat builders exposed to low levels of styrene--a feasibility study of a possible biomarker for acquired susceptibility.

Sensitivity to carcinogens and susceptibility for malignant diseases may be related to genetic predisposition, e.g. polymorphisms in toxicant-metabolizing enzymes or DNA repair deficiencies. The latter may also be acquired by exposure to substances that interfere with DNA repair processes. Application of the challenge assay to an exposed population may allow scientists to study the interference of DNA repair as an acquired susceptibility phenomenon. The assay was therefore used in a feasibility study to evaluate its application. A group of 14 workers exposed to low levels of styrene (mean < 100 mg/m3 styrene in air; 35 micrograms/l styrene in blood) and a reference of seven controls were investigated for structural chromosomal aberrations using FISH. The rate of exchange-type aberrations per 100 metaphases was 0.14 (95% CI, 0.05-0.31) in controls and 0.22 (95% CI, 0.13-0.36) in exposed workers. The difference is not statistically significant. Interaction with DNA repair was measured in the 14 workers and 2 historical controls using the challenge assay. Exchange-type aberrations per 100 metaphases after X-ray challenge of 1.66 Gy were 13.26 (10.53-16.50) and 16.19 (15.00-17.40) for the controls and exposed, respectively. The difference is statistically significant (p < 0.038). Among the exposed group, the challenge response was also significantly correlated with the cumulative lifetime exposure to styrene (R2 = 0.3996; p < 0.015) but not with the current exposure as measured in blood (R2 = 0.0226; p = 0.700). The challenge responses in the short-term and long-term exposed subgroups were 15.55 (14.23-16.96) and 17.90 (15.64-20.39), respectively, based on sample sizes of 5 and 9, respectively. The difference was not significant. Hence, data from our study are consistent with the hypothesis that long-term exposure to styrene can interfere with DNA repair activities. The lack of statistically significant differences in some of the data may be due to the small sample size and a possible confounding by age in our investigation. Additional data from our ongoing study should clarify this uncertainty.

Adult↗