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  • 1
    Electronic Resource
    Electronic Resource
    Isotopic variation as an index of sulphur pollution in lakes around Sudbury, Ontario (1978)
    [s.l.] : Nature Publishing Group
    Nature 273 (1978), S. 223-224 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The INCO nickel smelter stack at Copper Cliff, near Sudbury, is about 380 m tall and emits approximately 35,000 tons of SO2 daily5, or roughly 20% of all the SO2 emitted annually in Canada6. The plume from the stack usually rises to about 1,000 m after emission and occasionally travels for hundreds ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/273223a0
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  • 2
    Electronic Resource
    Electronic Resource
    Metal concentrations in chironomids in relation to the geochemical characteristics of surficial sediments (1991)
    Springer
    Archives of environmental contamination and toxicology 21 (1991), S. 202-211 
    Details
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract Concentrations of Fe, Mn, Al, Zn, Cu, and Cd were determined in Chironomidae (Diptera) sampled from three locations in six lakes ranging in pH from 5.0 to 6.5. Results of a two-way ANOVA with sample location and lake as the two co-factors showed that, in general, chironomid larvae metal concentrations were lake and sample site dependent (P〈0.05). To determine if differences in chironomid larval metal concentrations among the six lakes could be related to the geochemistry of the sediments, specifically concentrations of: organic matter, reducible Fe (Fe oxides), easily reducible Mn (Mn oxides) and metal (Fe, Mn, Al, Zn, Cu and Cd) associated with either the easily reducible, reducible and alkaline extract (organic) components of the sediment, a partial correlation analysis was employed. Chironomid Mn, Al, and Fe concentrations correlated positively with total sediment Mn, Al, and Fe concentrations, respectively, and negatively with organic matter; chironomid Zn and Cu concentrations correlated positively with an easily reducible measure of sediment Zn and Cu concentrations and negatively with sediment concentrations of reducible Fe. No combination of sediment geochemical variables significantly correlated with chironomid Cd concentrations. These results support the hypothesized action of reducible Fe (Fe oxides) modifying Zn and Cu accumulation by chironomids. In contrast, sediment organic matter rather than reducible Fe modifies Mn, Al, and Fe accumulation in chironomids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01055338
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  • 3
    Electronic Resource
    Electronic Resource
    The role of bisphosphonates in the treatment of bone metastases — the U.S. experience (1996)
    Springer
    Supportive care in cancer 4 (1996), S. 213-217 
    Details
    ISSN: 1433-7339
    Keywords: Bisphosphonates ; Aredia ; Bone metastases ; Pain ; Skeleton-related events
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Frequent complications of bone metastases include pain, pathologic fracture, hypercalcemia and spinal cord compression. Lytic bone metastases result from excessive activation of osteoclasts by tumor-produced cytokines. Aredia (pamidronate) is a potent bisphosphonate that inhibits osteoclast activation. In two dose-seeking phase I trials in patients with breast cancer and prostate cancer, repeated intravenous infusion of Aredia was shown to be safe and effective in reducing bone resorption and pain. In a randomized phase III trial of 377 patients with multiple myeloma, Aredia was administered in a dosage of 90 mg i.v. every 4 weeks. Compared with placebo, treatment with Aredia was associated with a significant decrease in bone pain and in the incidence and time to development of all skeleton-related events. Data from two phase III breast cancer trials each involving 300 patients are now being analyzed. The newer bisphosphonates can safely be used together with standard anticancer therapy to provide effective palliation of symptoms caused by lytic bone metastases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01682343
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  • 4
    Electronic Resource
    Electronic Resource
    Phase I trial of recombinant platelet factor 4 (rPF4) in patients with advanced colorectal carcinoma (1996)
    Springer
    Investigational new drugs 14 (1996), S. 387-389 
    Details
    ISSN: 1573-0646
    Keywords: platelet factor 4 (rPF4) ; angiogenesis inhibitor ; colorectal carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Background: Recombinant platelet factor 4 (rPF4) is a naturally occurring protein found in platelet alpha granules that can inhibit angiogenesis. Methods: In this Phase I trial, 9 patients with metastatic colorectal cancer who had failed 5-FU treatment received rPF4 at doses ranging from 0.3 to 3.0 mg/kg via 30-minute infusion. Three additional patients were treated with the 3 mg/kg dose over a 6-hour period of infusion. Results: The only toxicity encountered was mild leg twitching in 2/3 patients treated with the 6-hour infusion. One patient with a history of phlebitis developed a lower extremity deep venous thrombosis after the first dose of rPF4. A mild rise in fibrinogen level was noted in several patients. Of the 11 evaluable patients, there were no clinical responses to treatment. Conclusions: rPF4 is well tolerated at the doses and schedules tested. No clinical responses were observed. Prolonged infusion schedules should be investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00180815
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  • 5
    Electronic Resource
    Electronic Resource
    The management of hypercalcemia of malignancy (1995)
    Springer
    Supportive care in cancer 3 (1995), S. 123-129 
    Details
    ISSN: 1433-7339
    Keywords: Hypercalcemia of malignancy ; PTH-rP ; Bisphosphonates ; Osteoclast inhibition ; Bone metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hypercalcemia (HCM) occurs in 10–15% of all malignancies, predominantly in patients with solid tumors. This metabolic complication leads to significant morbidity and impairment of quality of life. Recent insights into the pathophysiology of HCM include an understanding of the role of parathyroid-hormone-related peptide and several cytokines secreted by tumors. The osteoclast plays a central role as the final common pathway through which these hormones and cytokines act to cause bone lysis. These findings have led to the development of new treatment strategies. Foremost among these has been the introduction of agents such as the newer bisphosphonates and gallium nitrate, which are potent inhibitors of osteoclast-mediated bone resorption. The clinician can now choose from an array of therapeutic approaches based on a consideration of the mechanisms of action, individual clinical circumstances, efficacy, toxicities and costs of available agents. In addition to their use in the management of HCM, non-toxic drugs that effectively inhibit osteoclast function, such as the bisphosphonates, are playing an emerging role in the palliative treatment of the more common clinical problems of painful lytic bone metastases and osteoporosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00365852
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  • 6
    Electronic Resource
    Electronic Resource
    Concentrations and distribution of Fe, Zn and Cu in tissues of the white sucker (Catostomus commersoni) in relation to elevated levels of metals and low pH (1989)
    Springer
    Hydrobiologia 176-177 (1989), S. 349-354 
    Details
    ISSN: 1573-5117
    Keywords: metal concentrations ; sediments ; fish ; pH ; Fe ; Cu ; Zn ; white sucker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract This study examines whether the process of lake acidification influences the accumulation of Fe, Zn and Cu in the tissues of the white sucker (Catostomus commersoni). Concentrations of Fe, Zn and Cu were measured in the liver, kidney and muscle of white sucker sampled from 4 acidic (pH range 4.8–5.3), 1 slightly acidic (pH = 5.8) and 3 circumneutral (pH = 6.3, 6.4) lakes located in south-central Ontario, Canada. Pearson product-moment correlation coefficients were used to determine relationships between average elemental concentrations in the 3 tissues and both sediment and water metal concentrations plus lake pH, DOC and alkalinity. Despite the 1000-fold difference in H+ concentration among the 8 study lakes, tissue concentrations of Fe, Zn and Cu did not correlate with lake pH. Average Fe, Zn and Cu tissue concentrations did not correlate with metal concentrations in lake water. Only Zn concentrations in the liver and muscle were correlated with Zn concentrations in the sediment (r = 0.83 and r = 0.88, P 〈 0.05). Iron and Cu were regulated by the white sucker over a wide range of lake pH and metal concentrations in both the water and sediment. In contrast, Zn tissue concentrations were correlated with sediment Zn concentrations, the latter are thought to result from Zn inputs of anthropogenic origin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00026569
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  • 7
    Electronic Resource
    Electronic Resource
    Uptake and tissue distribution of manganese in the white sucker (Catostomus commersoni) under conditions of low pH (1986)
    Springer
    Hydrobiologia 133 (1986), S. 117-125 
    Details
    ISSN: 1573-5117
    Keywords: lake acidification ; white sucker ; manganese ; lake sediments ; benthos ; redox conditions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Concentrations of manganese were determined in the liver, kidney, muscle and bone of white suckers (Catostomus commersoni) from five acid (pH 〈 5.8), and two circumneutral lakes in south-central Ontario. Manganese tissue concentrations were greater in fish captured from the most acidified lakes with the greatest concentrations of dissolved manganese. These fish had increased concentrations of manganese in the liver, as indicated by a comparison of liver:kidney manganese concentration ratios among the seven fish populations. Tissue concentrations of manganese from all populations either were negatively correlated (P 〈 0.05) or remained constant with fish size indicating homeostatic regulation of this metal. Manganese concentrations of the benthic fauna were positively correlated to sediment concentrations (R=0.30). Lake sediment manganese concentrations were significantly correlated to maximum lake depth (R=0.80, P 〈 0.03), with the concentrations in the top 0–1 cm dependent on the redox conditions in the seven lakes. Based on the seven lakes studied, manganese concentrations in the benthic-feeding white sucker correlated better with dissolved manganese, than with either the concentrations in food or surficial sediments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00031861
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  • 8
    Electronic Resource
    Electronic Resource
    Growth responses of yellow perch,Perca flavescens (Mitchill), to lake acidification in the La Cloche Mountain Lakes of Ontario (1980)
    Springer
    Environmental biology of fishes 5 (1980), S. 97-108 
    Details
    ISSN: 1573-5133
    Keywords: Acid precipitation ; Acid stress ; Growth rates ; Recruitment ; Stress indicator ; Water quality monitoring ; Fish mortality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Synopsis Acidification of the lakes of the La Cloche Mountains, Ontario, has reduced population densities of the yellow perch. Yellow perch of age groups 1 to 3 responded with increased rates of growth. Yellow perch of age groups 4 to 9 responded with reduced rates of growth. On the basis of these findings it is suggested that the growth rate of yellow perch may serve as a valuable indicator of environmental stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02391617
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacologic suppression of estrogens with aminoglutethimide as treatment of advanced breast carcinoma (1982)
    Springer
    Breast cancer research and treatment 2 (1982), S. 375-383 
    Details
    ISSN: 1573-7217
    Keywords: adrenal secretion rates ; aminoglutethimide ; antiestrogens ; aromatase inhibitors ; breast cancer ; estrogen receptor ; hormone ablation ; medical adrenalectomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent studies suggest that estrogens are the predominant hormones required for the growth of hormonedependent breast cancers in women. Traditional methods of lowering estrogens as treatment of breast cancer involve surgical removal of the ovaries, adrenals, or pituitary. Newer investigative strategies utilize blockade of estrogen action with antiestrogens or inhibition of estrogen synthesis. As reviewed previously, a regimen for pharmacologic suppression of estrogen production was developed which utilizes the aromatase/steroidogenesis inhibitor aminoglutethimide (AG) and replacement hydrocortisone (HC). The current paper updates recent mechanistic, clinical, and hormonal data regarding AG. The preservation of plasma androstenedione levels concomitant with marked estrone and estradiol suppression suggests that AG lowers estrogen production predominantly by blocking aromatization. The mechanism for sustained androstenedione production in the face of suppressed ketosteroids, glucocorticoids, and mineralocorticoids during AG administration was evaluated in dogs fitted with arteriovenous adrenal cannulae. Inhibition of the adrenal secretion of androstenedione with preservation of peripheral plasma levels of this steroid suggests stimulation ofextra-adrenal 3β-ol-dehydrogenase,Δ 5-Δ 4-isomerase activity by AG. Clinical studies revealed a 32% objective response rate to AG/HC in unselected patients and a 52% response in women with estrogen receptor positive tumors. Randomized trials indicated similar response rates to AG/HC vs hypophysectomy (AG/HC 47% vs Hypox 21%,p = NS), surgical adrenalectomy (AG/HC 52% vs surgical adrenalectomy 43%,p = NS) and antiestrogen therapy (AG/HC 36% vs tamoxifen 38%,p = NS). Cross-over data revealed that 50% of 94 patients initially responding to tamoxifen later experienced an objective regression to AG/HC. Only 25% of 93 tamoxifen nonresponders benefited later from AG/HC. Trends indicate that bone metastases may respond better to AG/HC (33%) than to tamoxifen (15%). Use of a computer-based data matrix allowed determination of whether patients escape from AG/HC induced estrogen and androgen suppression at the time of disease relapse. No trends towards escape from estrogen inhibition were apparent. However, in the objective responders to AG/HC, the weak androgens dehydroepiandrosterone-sulfate (DHEA-S) and androstenedione appeared to increase prior to disease relapse. DHEA-S but not androstenedione levels remained lower in the objective responders than in nonresponders at all phases of AG/HC therapy. Thus, the estrogens, but not androgens, remain constant during all phases of AG/HC treatment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01805879
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  • 10
    Electronic Resource
    Electronic Resource
    Aromatase inhibitor development for treatment of breast cancer (1995)
    Springer
    Breast cancer research and treatment 33 (1995), S. 19-26 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; aromatase ; estradiol ; hormonal therapy ; CGS 20267
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Inhibition of estrogen production provides effective therapy for patients with hormone-dependent breast cancer. The source of estrogens in premenopausal women is predominantly the ovary, but after the menopause, estradiol is synthesized in peripheral tissues through the aromatization of androgens to estrogens. Uptake from plasma is the primary mechanism for maintenance of estradiol concentrations in breast cancer tissue in premenopausal women, whereas several steps may be operant in postmenopausal women. These include enzymatic synthesis of estradiol via sulfatase, aromatase, and 17β-hydroxysteroid dehydrogenase in the tumor itself. Aromatization of androgens secreted by the adrenal to estrogens in peripheral tissues and transport to the tumor via circulation in the plasma provides another means of maintaining breast tumor estradiol levels in postmenopausal women. These various sources contribute to the high tissue estrogen levels measured in breast tumor tissue. To effectively suppress tissue concentrations of estrogens and circulating estradiol in postmenopausal patients, various aromatase inhibitors have been developed recently. These include steroidal inhibitors such as 4-hydroxy-androstenedione as well as non-steroidal compounds with imidazole and triazole structures. The most potent of these, CGS 20267, is reported to suppress levels of active estrogens (i.e., estrone, estrone sulfatase, and estradiol) by more than 95%. This compound can suppress both serum and 24-hrurine estrogens to a greater extent than produced by the second generation inhibitor, CGS 16949A. CGS 20267 is highly specific since it does not affect cortisol and aldosterone serum levels during ACTH stimulation tests nor sodium and potassium balance in 24-hr urine samples. These data suggest that CGS 20267 can be expected to bring improved response rates in the treatment of metastatic hormone-dependent breast cancer without substantial side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00666067
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