An update on Behçet''s disease

Behçet's disease (Adamantiades‐Behçet's disease, ABD) is a multisystemic inflammatory disease, the pathogenesis of which is still a mystery. Many questions are still to be answered and the available diverse data need to be brought together to be compared and analysed. There is at least consensus on the effect of possible, but currently unknown, environmental triggering factor(s) against a background of genetic susceptibility. The possible aetiological factors form a broad spectrum, with infectious agents being the most probable ones. Whatever the stimulus is, the target tissue seems to be the small blood vessels, with various consequences of either vasculitis and/or thrombosis in many organ systems. The endothelium seems to be the primary target in this disease; however, it may just be the subject of the bizarre behaviour of the immune system. The diverse existing data could be interpreted in favour of either explanation. A similar confusion exists about the thrombotic tendency in Adamantiades‐Behçet's disease, in terms of whether a primary hypercoagulability is present or whether it is secondary to inflammation. Recent interesting immunological data promise a way out of the existing dilemma. These findings will be outlined within the context of possible hypotheses and attention will be paid to further investigations that are needed.     

Circadian variation of plasma catecholamines in young and old men: relation to rapid eye movement and slow wave sleep.

Young and old healthy subjects with indwelling venous cannulae were found to undergo significant diurnal variations in plasma catecholamine levels. Both norepinephrine and epinephrine levels peaked in late morning and reached lowest values at night during sleep. Catecholamine levels were similar during slow wave and rapid eye movement sleep. While epinephrine levels were unaffected by age, norepinephrine levels were greater in older subjects by 28% during the day (at 1100 h; P less than 0.01) and by 75% at night (between 2200--0900 h; P less than 0.01). Older subjects slept less well; they had 90% less stage 4 sleep, 27% less rapid eye movement sleep, and twice as much wakefulness at night (P less than 0.05). These findings raise the possibility that this well known age effect on sleep may be related to increased sympathetic nervous system activity.     

Beta-adrenergic regulation of insulin secretion: evidence of tissue heterogeneity of beta-adrenergic responsiveness in the elderly.

Aging is associated with reduced beta-adrenergic receptor (beta-AR) function in several tissues. If this age effect on beta-ARs also applies to the pancreatic B-cell, it would result in relatively unopposed alpha-adrenergic inhibition of insulin secretion with adrenergic stimulation during stress states. This study compared insulin secretory responses to beta-AR stimulation (multiple IV doses of isoproterenol) with cardiac and circulating mononuclear lymphocyte (MNL) beta-AR responses in 9 healthy, non-obese young subjects, and 9 healthy, non-obese old subjects. We found no age-related decrease in the relationship between isoproterenol dose and insulin response. In contrast, the old subjects had significantly reduced heart rate responses to isoproterenol and generally lower MNL beta-AR function. We conclude that pancreatic B-cell beta-AR mediated function is not impaired in the elderly, suggesting that heterogeneity of tissue beta-AR mediated function exists in this population. Diminished pancreatic islet beta-AR mediated function does not appear to be a mechanism that predisposes healthy older individuals to the development of stress hyperglycemia.     

Prostaglandin E2 metabolite levels during diabetic ketoacidosis

Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.