To delineate the physiological effects of aging on basal levels and temporal patterns of neuroendocrine secretions, the 24-h profiles of cortisol, thyroid-stimulating hormone (TSH), melatonin, prolactin, and growth hormone (GH) levels were simultaneously obtained at frequent intervals in eight healthy, active elderly men, age 67-84 yr and in eight young male adults, age 20-27 yr. The study was preceded by an extended period of habituation to laboratory conditions, and sleep was polygraphically recorded. Mean cortisol levels in the elderly were normal, but the amplitude of the circadian rhythm was reduced. Circulating levels of daytime and nighttime levels of both TSH and GH were greatly diminished in old age. In contrast, prolactin and melatonin concentrations were decreased during the nighttime only. The circadian rises of cortisol, TSH, and melatonin occurred 1-1.5 h earlier in elderly subjects, and the distribution of rapid-eye-movement stages during sleep was similarly advanced, suggesting that circadian timekeeping is modified during normal senescence. Despite perturbations of sleep, sleep-related release of GH and prolactin occurred in all elderly men. Age-related decreases in hormonal levels were associated with a decrease in the amplitude, but not the frequency, of secretory pulses. These findings demonstrate that the normal process of aging involves alterations in the central mechanisms controlling the temporal organization of endocrine release in addition to a reduction of secretory outputs.

There is no standard therapy for elderly patients with high-riskIn contrast, in several clinical studies with high-dose DAC an myelodysplastic syndrome (MDS). The treatment options of antileukaemic effect was seen with myelosuppression as the low-dose Ara-C and haematopoietic growth factors are disapmain toxic effect. [16][17][18] We conducted a phase II study with pointing in regard to response rate or response duration. We low-dose DAC to study the effectiveness of this drug in MDS Twenty-nine elderly patients with progressive MDS (17 male,Myelotoxicity is its major adverse effect.12 female) who could not be entered in protocols for more Keywords: myelodysplastic syndrome; 5-Aza-2Ј-deoxycytidine;intensive chemotherapy due to their age and/or substantial elderly; continuous infusion; low-dose therapy comorbidity were entered in this study. All patients showed bad prognostic features such as high blast cell count in the bone marrow, anemia, thrombocytopenia or cytogenetic Introduction abnormalities related to a bad prognosis. 7,8 Table 1 shows the characteristics of the patients. The median age was 72 years The myelodysplastic syndromes (MDS) consist of a hetero-(range 58-82 years). The following myelodysplastic subtypes geneous group of clonal haemopathies characterized by matuwere included: RA four, RARS two, RAEB 11, RAEB-T nine, ration defects resulting in ineffective haematopoiesis and so CMML one, secondary (sAML) two patients. The last two in various combinations of anemia, leucopenia and thrompatients were known to have progressive MDS but at entry to bocytopenia.1,2 MDS frequently occur in elderly patients and the study their bone marrow revealed 30-40% of blasts, thus some of the cases are secondary or related to long-term bone they were scored as sAML. All patients but one (No. 25) were marrow damage after radiation or chemotherapy.3,4 Several blood and/or platelet transfusion-dependent. In 20 patients a studies delineating the course and the prognosis of MDS more or less severe comorbidity was present not affecting showed a poor median survival especially in patients with renal and/or hepatic function. CMML, RAEB and RAEB-T. 5,6 A high blast cell count, the grade of (pan)cytopenia and some of the karyotypic abnormalities associated with MDS predict such a poor outcome. 7,8 Therapy The treatment of MDS remains a challenge for the clinician, especially in elderly patients, because no currently available 5-Aza-2′-deoxycytidine (DAC) was a gift from Pharmachemie, therapy has been shown to be generally effective.Haarlem, The Netherlands. In the first 21 patients DAC was 5-Aza-2′-deoxycytidine (DAC) is a pyrimidine analogue that given by continuous infusion for 72 h starting with a dose of inhibits DNA methylation.9 It has been proposed that the inhi-50 mg/m 2 /24 h. Courses were repeated every 6 weeks when bition of DNA methylation by deoxycytidine analogues is no serious clinical problems other than (pan)cytopenia were responsible for gene activation and so to the induction of cell present. No dose redu...

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Both ageing and vitamin C (VC) deficiency result in immune defect. Since low serum and tissue levels of VC are found in the elderly, we have in a placebo-controlled study, tested the effect of VC supplements (500 mg/day i.m. for 1 month) on various immune parameters. Indeed, VC enhances the proliferative response of T lymphocytes in vitro, and the tuberculin skin hypersensitivity in vivo. Neither the serum concentrations of IgA, IgG and IgM, nor the proportion of E-rosette-forming cells were modified. No significant change was observed in the placebo-treated group.

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