In a randomized, double-blind, placebo-controlled study, we assessed the efficacy of an ACTH(4–9) analogue, Org 2766, in the prevention of cisplatin neuropathy in 55 women with ovarian cancer. The ...analogue was given subcutaneously in a dose of 0.25 mg (low dose) or 1 mg (high dose) per square meter of body-surface area before and after treatment with cisplatin and cyclophosphamide (75 and 750 mg per square meter every three weeks). The threshold of vibration perception was used as the principal measure of neurotoxicity.
After four cycles of chemotherapy, the mean (±SEM) threshold value for vibration perception in the placebo group increased from 0.67±0.12 to 1.61±0.43 μm of skin displacement (P<0.0001). In the high-dose treatment group, there was no increase in the threshold value after four cycles (from 0.54±0.12 to 0.50±0.06 μm). After six cycles of chemotherapy, the threshold value was 5.87±1.97 μm in the placebo group (more than an eightfold increase from base line), as compared with 0.88±0.17 μm (less than a twofold increase) in the high-dose treatment group (P<0.005). In the high-dose group, fewer neurologic signs and symptoms were recorded than in the placebo group. With the lower dose of the analogue, these protective effects were less prominent. No side effects were seen after treatment with Org 2766. The rates of clinical response to chemotherapy were similar in all groups.
These results suggest that Org 2766 can prevent or attenuate cisplatin neuropathy without adversely affecting the cytotoxic effect of the drug. (N Engl J Med 1990; 322:89–94.)
MELANOCORTINS (ACTH and α-melanocyte-stimulating hormone-like peptides) are known to affect the function of the nervous system in animals and humans.
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Evidence obtained from studies in animals suggests that these peptides exert a beneficial effect on mechanisms of peripheral-nerve repair.
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After peripheral-nerve crush injury, ACTH and a number of derived fragments (Fig. 1) have been reported to accelerate recovery and enhance nerve regeneration in rats at the histologic, electrophysiologic, and functional levels.
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Recovery was also enhanced after transection of the nerve.
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The mechanism of action is not known, but evidence suggests the presence of an α-melanocyte-stimulating hormone-like substance in degenerating
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or . . .
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric ...manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study.
After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out.
Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures.
Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.
In view of recent progressive insight in the diagnosis and treatment of leptomeningeal metastases of solid tumours, a new guideline has been designed on the initiative of the Dutch Association of ...NeuroOncology and the Netherlands Society of Neurology, with methodological support from the Dutch Institute for Healthcare Improvement (CBO). - There are no neurological symptoms or signs, nor MRI characteristics that are unique to leptomeningeal metastasis. However, clinical suspicion of leptomeningeal metastasis in a patient known to have cancer, in combination with specific MRI characteristics is sufficient to make the diagnosis. If MRI or CT results are negative or inconclusive cerebrospinal-fluid assessment should be conducted. - Management of care of patients with leptomeningeal metastasis without brain metastases can be based on a series of categories that have been developed using prognostic factors such as Karnofsky performance status, serious encephalopathy or neurological dysfunction, systemic disease, sensitivity of the tumour for chemotherapy or hormonal treatment - In the context of meaningful palliation, systemic treatment, if necessary in combination with radiotherapy to clinically relevant sites, is preferable to intrathecal chemotherapy. - Intrathecal chemotherapy combined with local radiotherapy is recommended if effective systemic treatment is not available, and if the tumour is potentially sensitive to methotrexate, cytarabine or thiotepa. The combination of intrathecal methotrexate and whole-brain radiotherapy should be avoided.
The determination of the in situ reduction levels of cytochromes b and c in growing bacteria is achieved by coupling a chemostat with a dual wavelength spectrophotometer. Visible light absorption ...spectra of cytochromes present in bacterial cells actively growing in a chemostat at a specific growth rate of 0.1 h-1 are recorded. This is accomplished by transporting the emitted light from the spectrophotometer via glass fibers to one side of the chemostat vessel and detecting the transmitted light via a photomultiplier at the other side. The vessel itself is enclosed in a dark box, which contains mirrors on the inside surfaces. The reduction levels of cytochromes b and c during steady state in chemostat cultures are expressed as percentage absorbance of fully reduced cytochromes in the alpha-region of the spectrum. Steady state spectra are recorded in N2-fixing, succinate-limited continuous cultures of Azorhizobium caulinodans at dissolved oxygen tensions in the range between 0.1 and 3.5% O2. Spectra of fully reduced cytochromes are obtained on the basis of spectra recorded after having reached anoxic conditions by sparging pure nitrogen gas through the culture. These spectra of cytochromes b and c reduced by endogenous substrates are corrected as to give the spectrum of fully reduced cytochromes. The respective contributions of cytochromes b and c to spectra in the alpha-region are estimated by deconvolution using best-fit analysis. Using this in situ technique it is observed that at each dissolved oxygen tension the reduction level of the cytochromes b is higher than that of the cytochromes c.
Investigations into inter-level relations in computer science, biology and psychology call for an empirical turn in the philosophy of mind. Rather than concentrate on a priori discussions of ...inter-level relations between "completed" sciences, a case is made for the actual study of the way inter-level relations grow out of the developing sciences. Thus, philosophical inquiries will be made more relevant to the sciences, and, more importantly, philosophical accounts of inter-level relations will be testable by confronting them with what really happens in science. Hence, close observation of the ever-changing reduction relations in the developing sciences, and revision of philosophical positions based on these empirical observations, may, in the long run, be more conducive to an adequate understanding of inter-level relations than a traditional a priori approach.
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Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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