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Biomedical subjects

D Pedersen

Publications and source records attributed to D Pedersen.

At least 19 recordsLinked to original sources

Prognostic indicators for malignant tumours of the parotid gland.

The best treatment of malignant parotid tumours still remains to be defined, and a better knowledge about the tumour features that predict the treatment result is needed. The histological classification of parotid tumours may present difficulties on account of their great morphological diversity. In a series of 152 patients with a malignant tumour of the parotid gland, the prognostic factors and treatment results were investigated over a 25-year period. Treatment consisted of surgery, radiation therapy or a combination (49%, 13% and 38% respectively). Crude 5-year survival was 50% with significant differences related to stage (stage I, 65%; stage II, 50%; stage III, 21%; and stage IV, 9%). With respect to histopathology, the adenoid cystic carcinomas and the acinic cell carcinomas had the best prognosis (76% and 67% 5-year crude survival and 53% and 67% 10-year crude survival respectively). There was a significant difference in crude survival between well/intermediate and poorly differentiated tumours (P = 0.007). In a Cox hazard regression analysis including 136 patients and using death from cancer as the end-point, the following parameters were independent prognostic predictors: T-classification (P = 0.002), M-classification (P < 0.0001), N-classification (N+versus N0) (P = 0.005), local invasion (P = 0.003) and histological differentiation of the tumour (P = 0.03). The TNM system is a good predictor of treatment outcome for malignant parotid tumours. The use of a combination of clinical and histological factors will assist the design of treatment strategies for parotid gland tumours.

Adolescent↗

Increased peak contact stress after incongruent reduction of transverse acetabular fractures: a cadaveric model.

BACKGROUND: The objective of this study was to determine the peak contact pressure with varying degrees of articular cartilage step-off in a transtectal acetabular fracture model. METHODS: Five fresh frozen cadaveric hip joints were potted in a custom loading fixture. The five specimens were then tested at loads of 445 N (newton) (100 lb) and 1,335 N (300 lb) intact and after a transverse osteotomy at step-off levels from 0 to 5 mm in 1-mm increments. RESULTS: Articular cartilage step-off of greater than 1 mm led to significantly increased contact stress at the loaded acetabular articular surface. Mean peak pressure measured at 1,335 N of loading in all intact specimens before the osteotomy was approximately 10 MPa. Peak pressure after a transverse acetabular fracture did not change when the fracture was perfectly reduced. At 1 mm of step-off, the peak pressure increased by approximately 20% but was not statistically significant. With step-off of > 2 mm or greater, the peak pressure increase was approximately 50% and was statistically significant. CONCLUSION: On the basis of our study, transverse acetabular fractures with greater than 1 mm of displacement can lead to significant increase in peak pressure at the articular surface.

Acetabulum↗

Genetic control of natural variation in Arabidopsis glucosinolate accumulation.

Glucosinolates are biologically active secondary metabolites of the Brassicaceae and related plant families that influence plant/insect interactions. Specific glucosinolates can act as feeding deterrents or stimulants, depending upon the insect species. Hence, natural selection might favor the presence of diverse glucosinolate profiles within a given species. We determined quantitative and qualitative variation in glucosinolates in the leaves and seeds of 39 Arabidopsis ecotypes. We identified 34 different glucosinolates, of which the majority are chain-elongated compounds derived from methionine. Polymorphism at only five loci was sufficient to generate 14 qualitatitvely different leaf glucosinolate profiles. Thus, there appears to be a modular genetic system regulating glucosinolate profiles in Arabidopsis. This system allows the rapid generation of new glucosinolate combinations in response to changing herbivory or other selective pressures. In addition to the qualitative variation in glucosinolate profiles, we found a nearly 20-fold difference in the quantity of total aliphatic glucosinolates and were able to identify a single locus that controls nearly three-quarters of this variation.

Arabidopsis↗

Occupational exposure to carcinogens in the European Union.

OBJECTIVES: To construct a computer assisted information system for the estimation of the numbers of workers exposed to established and suspected human carcinogens in the member states of the European Union (EU). METHODS: A database called CAREX (carcinogen exposure) was designed to provide selected exposure data and documented estimates of the number of workers exposed to carcinogens by country, carcinogen, and industry. CAREX includes data on agents evaluated by the International Agency for Research on Cancer (IARC) (all agents in groups 1 and 2A as of February 1995, and selected agents in group 2B) and on ionising radiation, displayed across the 55 industrial classes. The 1990-3 occupational exposure was estimated in two phases. Firstly, estimates were generated by the CAREX system on the basis of national labour force data and exposure prevalence estimates from two reference countries (Finland and the United States) which had the most comprehensive data available on exposures to these agents. For selected countries, these estimates were then refined by national experts in view of the perceived exposure patterns in their own countries compared with those of the reference countries. RESULTS: About 32 million workers (23% of those employed) in the EU were exposed to agents covered by CAREX. At least 22 million workers were exposed to IARC group 1 carcinogens. The exposed workers had altogether 42 million exposures (1.3 mean exposures for each exposed worker). The most common exposures were solar radiation (9.1 million workers exposed at least 75% of working time), environmental tobacco smoke (7.5 million workers exposed at least 75% of working time), crystalline silica (3.2 million exposed), diesel exhaust (3.0 million), radon (2.7 million), and wood dust (2.6 million). CONCLUSION: These preliminary estimates indicate that in the early 1990s, a substantial proportion of workers in the EU were exposed to carcinogens.

Carcinogens↗

Is your HMO too stingy?

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Health Maintenance Organizations↗

The molecular basis of quantitative genetic variation in central and secondary metabolism in Arabidopsis.

To find the genes controlling quantitative variation, we need model systems where functional information on physiology, development, and gene regulation can guide evolutionary inferences. We mapped quantitative trait loci (QTLs) influencing quantitative levels of enzyme activity in primary and secondary metabolism in Arabidopsis. All 10 enzymes showed highly significant quantitative genetic variation. Strong positive genetic correlations were found among activity levels of 5 glycolytic enzymes, PGI, PGM, GPD, FBP, and G6P, suggesting that enzymes with closely related metabolic functions are coregulated. Significant QTLs were found influencing activity of most enzymes. Some enzyme activity QTLs mapped very close to known enzyme-encoding loci (e.g., hexokinase, PGI, and PGM). A hexokinase QTL is attributable to cis-acting regulatory variation at the AtHXK1 locus or a closely linked regulatory locus, rather than polypeptide sequence differences. We also found a QTL on chromosome IV that may be a joint regulator of GPD, PGI, and G6P activity. In addition, a QTL affecting PGM activity maps within 700 kb of the PGM-encoding locus. This QTL is predicted to alter starch biosynthesis by 3.4%, corresponding with theoretical models, suggesting that QTLs reflect pleiotropic effects of mutant alleles.

Analysis of Variance↗

The relevance of anthropology for tropical public health: a historical perspective.

Despite the fact that tropical diseases have long been linked to human behaviour and local cultures, the written record of anthropologists involved in the study of tropical disease is relatively recent. In this article, the authors review how anthropologists have shifted their focus from the ecological modeling of disease transmission to the more recent cultural-epidemiological and historical approaches. The list of authors reviewed does not pretend to be exhaustive but rather is intended to reveal the co-existence of multiple paradigms in explaining the emergence of tropical disease within cultures.

Anthropology, Cultural↗

Beyond TPH: health-based evaluation of petroleum hydrocarbon exposures.

The term "total petroleum hydrocarbons" (TPH) is a widely used, but loosely defined, parameter quantified by a number of different methodologies for expressing the aggregate amount of petroleum hydrocarbon compounds (PHCs) in a sample. Because of the shortcomings associated with comparing data from different methods, and the difficulty of assessing potential toxicities of complex mixtures of hydrocarbons, a new approach at more fully and explicitly defining the PHC composition of samples and predicting human noncancer health risks from those exposures has been developed. This new approach is the subject of this paper. This method can be used to perform site-specific risk assessments or to develop health-based cleanup standards for petroleum hydrocarbons. The technique divides the broad chemical classes of PHC (i.e., saturated versus unsaturated) into subgroups of compounds based on numbers of carbon atoms in the compounds within each subgroup. The mass of compounds in each subgroup is then translated into discrete estimates of health risk for specified exposure scenarios. The subgroups were identified from qualitative and quantitative changes in the nature of noncancer toxicities recorded in the literature. For saturated compounds, toxicity changes as carbon chain length increases (measured by numbers of carbon atoms). A "reference compound" was chosen for each range of compounds, usually because its toxicity was relatively well characterized. A published oral reference dose (RfD) was identified for these compounds, or in the absence of a published value, an oral dose-response value was developed from available toxicity information. For saturated PHCs (alkanes, cycloalkanes, and isoalkanes) the subgroups' reference compounds and assigned toxicity value used are C5 to C8 (n-hexane, 0.06 mg/kg/day); C9 to C18 (n-nonane, 0.6 mg/kg/day); and C19 to C32 (eicosane, 6.0 mg/kg/day). For unsaturated compounds (aromatics), one reference RfD was identified for all compounds: C9 through C32 (pyrene, 0.03 mg/kg/day). Dependent upon the analytical technique used for separation of compounds, the unsaturated alkenes may be grouped and subsequently quantified with either the saturate or unsaturate groups. The implications of possible association with either group and contributions to risk estimates are probably not significant. Alkenes make up a small fraction of most fuel products, and they bear structural similarity to the alkanes and are not particularly toxicologically active. If grouped analytically with the aromatics the alkene contribution to toxicity estimates would likely be minor and not be an underestimate of its true toxicity. The mass of PHC in each segment of a chromatogram is quantified and converted to a medium-specific concentration which is then entered into standard medium intake equations to arrive at a daily dose of PHC. This dose is then used with the toxicity value identified for the particular segment of the chromatogram to derive a hazard quotient. The quotients can then be summed across fractions to yield a total hazard index. The noncancer health risks from the aromatics benzene, toluene, and xylenes are evaluated separately using standard risk assessment techniques.

Alkanes↗

Disease ecology at a crossroads: man-made environments, human rights and perpetual development utopias.

There is a growing body of critical literature on health, development and environmental sustainability in a world of finite resources and overburdened ecosystems. The ethics of progress and perpetual development in pursuit of unlimited economic growth and ever-expanding markets are no longer viable, given the constraints imposed on the life-support systems of the biosphere and a finite resource base, which poses the most serious threat to life on Earth. Despite increasing evidence of the linkages between economic growth and environmental deterioration and a rhetoric expressed in a growing body of laws, regulations, accords and global "agendas" at the national and international level, there are all too few success stories in reversing or even slowing down the current trends of ecosystem degradation and decreasing cultural and biological diversity. On the contrary, there is evidence that environmental stress and deterioration are increasing, and the impact on the mental, physical and social health and well-being of populations is more significant now than in any previous time in history. The fragmentation of countries, the rise of nationalism and ethnic conflict, the decimation of indigenous nations and human rights abuses are often closely interrelated with environmental degradation and development initiatives. This paper reviews some of the concepts and underlying values of the main "models" developed by health and social scientists for interpreting this reality, with the aim of stimulating debate that could lead to the adoption of a larger and more comprehensive framework for analysing the interactions between human health, development and environmental change.

Cultural Evolution↗

Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group.

PURPOSE: To test for possible correlations between dose of single-drug epirubicin and efficacy/toxicity in postmenopausal women with metastatic breast cancer. The study also included analysis of a correlation between pharmacokinetic and pharmacodynamic parameters. PATIENTS AND METHODS: Two hundred eighty-seven women were randomized to receive either 40, 60, 90, or 135 mg/m2 of epirubicin intravenously (IV) every 3 weeks. Treatment consisted of first-line cytotoxic therapy for metastatic disease. In patients with early progressive disease after either 40 or 60 mg/m2, dose escalation to 135 mg/m2 was performed. A full pharmacokinetic analysis was performed in 78 patients. RESULTS: Among 263 eligible patients, an increase in response rate and time to progression was found with an increase in dose from 40 to 90 mg/m2, while no increase in efficacy was found from 90 to 135 mg/m2. Multivariate analysis, using the Cox proportional hazards model with time to progression as the end point, confirmed that epirubicin dose more than 60 mg/m2 was an independent prognostic covariate. Furthermore, a significant association was established between randomized dose and both hematologic and nonhematologic toxicity. No association between pharmacokinetic parameters and efficacy parameters was demonstrated. On the other hand, a significant correlation between pharmacokinetic parameters and both hematologic and nonhematologic toxicity was found. CONCLUSION: An increase in dose of epirubicin from 40 to 90 mg/m2 is accompanied by increased efficacy. Further increases in dose do not yield increased efficacy. A positive correlation between epirubicin dose and toxicity, as well as a correlation between pharmacokinetic parameters and toxicity, was also established.

Adult↗

Is there a radiobiologic basis for improving the treatment of advanced stage cervical cancer?

The success of radiotherapy in eradicating the primary tumor in patients with locally advanced cervical cancer is limited by normal tissue tolerance. Systematic recording of morbidity and treatment parameters is therefore very important for radiobiologic treatment optimization and clinical decision making. There is substantial evidence that fractionation schedules employing large doses per fraction lead to a loss of therapeutic ratio. A similar argument could be used for high-dose-rate (HDR) brachytherapy that should also be administered in small dose fractions. However, HDR brachytherapy might convey some advantage to physical dose distribution that should be weighed against the radiobiologic advantages of low-dose-rate (LDR) continuous irradiation. Increasing overall treatment time reduces local control probability, whereas a shorter overall treatment time by accelerated fractionation may improve the therapeutic ratio, at least in fast-growing tumors. Hypoxia and reduced oxygen delivery are associated with poor radiation response. Anemia should be compensated, if necessary. The role of hypoxic modification needs to be further explored. In the future, the therapeutic ratio may also be improved by the use of chemical and biologic response modifiers. Tumors are heterogeneous with respect to intrinsic radiosensitivity, proliferation parameters, and extent of hypoxia. Until a detailed prognostic profile can be obtained for each patient, optimal curative radiotherapy must aim for a sufficient dose, short overall treatment time, hypoxic modification, and LDR or low dose per fraction.

Brachytherapy↗

Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study.

A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

Aged↗

Prognostic value of pretreatment factors in patients with locally advanced carcinoma of the uterine cervix treated by radiotherapy alone.

The prognostic effect of pretreatment patient- and tumor characteristics, and the influence of radiotherapy schedule on local control, distant metastases, and crude survival were analyzed in 424 consecutive patients with FIGO stage IIB (n = 137), IIIA (n = 10), IIIB (n = 211) and IVA (n = 66) cancer of the uterine cervix. All patients were given radiotherapy alone. From 1974 and through 1977, the external and intracavitary combined radiotherapy was given continuously in 4 to 6 weeks. From 1978 and through 1983, the treatment policy was changed to split-course radiotherapy by introducing planned pauses, resulting in an overall treatment time of 10 to 12 weeks. The results were estimated by univariate actuarial- and Cox multivariate regression analyses. Multivariate analysis showed that significant adverse variables for local control were large lateral tumor diameter, young age, low hemoglobin at time of admission, many pregnancies, split-course strategy, and high FIGO stage. Risk of metastases increased with decreasing hemoglobin, increasing malignancy grade and split-course treatment. Poor survival probability were related to large lateral tumor diameter, high malignancy grade and FIGO stage, low hemoglobin, split-course therapy, and adeno/adenosquamous tumor type.

Actuarial Analysis↗