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211.
Clinical pharmacology of deoxycoformycin 总被引:3,自引:0,他引:3
Deoxycoformycin (DCF) is an inhibitor of adenosine deaminase (ADA). Twenty-one courses of DCF were administered to 13 patients ranging in age from 15 to 78 yr. Eight patients had T-cell disorders, and five patients had non-T-cell malignancies. The i.v. bolus dose was escalated from 5 to 30 mg/sq m/day, and the duration of the courses ranged from 1 to 5 days. The DCF plasma half-life ranged from 4.9 to 6.2 hr and was independent of dose. The dose-limiting toxicities involved the central nervous system (CNS) and the kidneys. Other toxicities included bronchitis, decreases in hematocrit, arthralgias, and myalgias. Mortality was encountered in three patients. These toxic effects may have been secondary to the accumulation of the metabolites adenosine and deoxyadenosine. Deoxyadenosine and adenosine were both detectable in plasma (10(-6) M) and in urine (10(-3) M). Two partial remissions were observed: one in a patient with T-cell ALL and another in a patient with mycosis fungoides. Minimal responses characterized by either declines in peripheral blast counts or partial resolution of adenopathy were observed in five other patients. No responses were observed in six patients. These observations suggest that DCF is effective in the treatment of T-cell lymphoid malignancies. 相似文献
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PP Agrawal AK Bahadur PK Mohanta K Singh AK Rathi 《Journal of Medical Imaging and Radiation Oncology》2006,50(3):201-205
Nine patients with a histologically proven diagnosis of chordoma seen at the Department of Radiation Oncology, Maulana Azad Medical College and Lok Nayak Hospital between January 1999 and December 2004 were retrospectively reviewed with respect to age, sex, presentation, location of tumour, treatment, response, recurrence, metastasis and follow up. Chordoma constituted 0.07% of total cancer cases registered over 6 years. Out of nine patients, eight were males and one was female with median age at time of diagnosis 52 years (range 34–68 years). All had sacrococcygeal lesions except one who had a spheno‐occipital lesion. Seven patients had undergone either subtotal or gross total resection whereas only biopsy had been carried out in two of them. All patients received radiation therapy, seven in a postoperative setting and two for palliation. Follow‐up period ranged from 2 to 50 months. Four patients died – the first after fourth fraction of radiation, second after 10 days of treatment, third of progressive lesion in sphenoidal region despite resection and radiation and fourth of local recurrence in the sacrococcyx. One patient developed distant metastases in the lungs and subcutaneous tissue over the scalp along with local recurrence; he is still alive. Two patients are locally free of disease whereas the other two were lost to follow up. The present analysis was undertaken to review our institutional experience with an aim to provide a practical approach to these tumours. In this report, these cases are discussed and the published works have been reviewed for the optimal management of patients with chordoma. 相似文献
214.
Thomas Courret Thomas Tourdias Jean Papaxanthos Julien Labreuche Florent Gariel Jean-Sebastien Liegey Stephane Olindo Pauline Renou Jerome Berge Xavier Barreau Sharmila Sagnier Patrice Menegon Ludovic Lucas Pierre Briau Mathilde Poli Sabrina Debruxelles François Rouanet Vincent Dousset Igor Sibon Gaultier Marnat 《European journal of neurology》2023,30(2):380-388
215.
Adlaïde A Mohr Alba M Garcia-Serrano Joo PP Vieira Cecilia Skoug Henrik Davidsson Joo MN Duarte 《Journal of cerebral blood flow and metabolism》2021,41(7):1734
The hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders. While mouse models have been extensively employed for understanding the mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and high-sucrose diet (HFHSD) for seven days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner. 相似文献
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218.
Rudofsky G Tsioga M Reismann P Leowardi C Kopf S Grafe IA Nawroth PP Isermann B 《European journal of medical research》2011,16(8):375-380
Background
Postoperative hyperthyroidism occurs in approximately one third of patients following parathyroidectomy due to primary hyperparathyroidism (PHP), but has only rarely been described in secondary hyperparathyroidism (SHP). The frequency, course, and laboratory markers of postoperative hyperthyroidism in SHP remain unknown. Our purpose was to evaluate the frequency and the clinical course of postoperative hypcrthyroidism following surgery of SHP and to determine the diagnostic value of thyroglobulin in this setting.Material and Methods
A total of 40 patients undergoing parathyroidectomy because of SHP were included in this study. Thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fl4), and thyroglobulin (Tg) were determined one day before and on day 1, 3, 5, 10, and 40 after surgery. At each of these visits patients were clinically evaluated for signs or symptoms of hyperthyroidism.Results
Biochemical evidence of hyperthyroidism was evident in 77% of patients postoperatively despite of preoperatively normal serum levels. TSH dropped from 1.18 ± 0.06mU/L to 0.15 ± 0.07mU/L (p = 0.0015). Free triiodothyronine (fT3) and fT4 levels increased from 2.86 ± 0.02ng/L and 10.32 ± 0.13ng/L, respectively, to their maximum of 4.83 ± 0.17ng/L and 19.35 ± 0.58ng/L, respectively. Thyroglobulin levels rose from 3.8 ± 0.8ng/mL to 111.8 ± 45.3ng/mL (p < 0.001). At day 40 all thyroid related laboratory values were within normal range. Correlation analysis of postoperative values revealed significant correlations for lowest TSH (r = -0.32; p = 0.038), and highest fT3 (r = 0.55; p < 0.001) and fT4 levels (r = 0.67; p < 0.001) with Tg.Conclusion
Transient hyperthyroidism is frequent after parathyroidectomy for SHP with Tg being a suitable marker. Awareness of this self-limiting disorder is important to avoid inappropriate and potentially harmful treatment. 相似文献219.
E Grossini C Molinari PP Caimmi F Uberti G Vacca 《British journal of pharmacology》2009,156(2):250-261