Interrelations among plasma renin activity (PRA), aldosterone and cortisole levels, 0lood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P less than 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P less than 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.

Interrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamiens, plasma and blood volumes, exchangeable body sodium and blood pressure wwere studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r= greater than 0.34; p less than 0.05), with significant differences in mean values between young and elderly subjects (p less than 0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was no statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly ( + 50%; p less than 0.02), but not in young ( --10%) or middle-aged ( --8%) subjects. Blood pressure correlated with age ( r =0.35; p less than 0.05) or noradrenaline excretion rate ( r= 0.34) in the entire study population and with blood volume in the elderly ( r = 0.68), but not in the young or middle-aged study. Groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Further more, these data are conssitent with the possiblity that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.

We have studied the frequency of p53 mutations in genomic DNA extracted from peripheral blood or the spleen of 61 patients with hairy cell leukemia using PCR-SSCP and automated cycle sequencing. We identified exon 5-8 mutations in 17 cases, corresponding to a frequency of 28%. In four cases, mutations were localized in exon 5; one patient with atypical HCL had a mutation in exon 6 at the 3Ј boundary; five cases showed mutations in exon 7, while exon 8 was found to be mutated in seven cases. The mutations found could be divided into three major categories: structural (n = 9), inactivating (n = 6), and neutral (n = 2) mutations. None of the three transitions found occurred at CpG dinucleotides. The rate of p53 mutations found in this large cohort of HCL patients is unexpectedly high as in other non-Hodgkin lymphomas p53 mutations predict for poor treatment outcome. The character of the mutations we have found is entirely different from that described in other hematologic malignancies. Leukemia (2000) 14, 706-711.

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