Acute GVHD (aGVHD) is a major cause of morbidity and mortality after unrelated BMT (UBMT). Our purpose was to analyze the role of extracorporeal photochemotherapy (ECP) in controlling grade II-IV aGVHD in children given UBMT. Of 41 consecutive children, 31 developed grade II-IV aGVHD after UBMT: 16 had a good response to steroids (GR group), whereas 15 underwent ECP (ECP group) within 100 days of UBMT. Eligibility criteria for starting ECP were steroid resistance, dependence or viral reactivations. Criteria for judging response to aGVHD treatment were that the resolution of all signs were considered a complete response (CR), at least a 50% improvement was classified as a partial response (PR) and stable or progressive disease was judged as no response (NR). On completing ECP, the CR rate was 73%, whereas the GR group had a CR rate of 56% by day 100. The 2-year overall survival and progression-free survival rates were 57 and 67% in the GR group vs 85 and 87% in the ECP group. Our data seem to suggest that ECP may improve outcome in patients after UBMT. These findings need to be confirmed in a larger population.

ATHEROSCLEROSISBRITTsIHI 507 thrombogenic concept of atheroma. It is suggested that more detailed studies of the small lipid-containing arterial lesions in animals and of the comparatively rare cases of atherothrombosis might lead to a better understanding of essentially similar lesions in man. Fig. 1; 92% of the patients were men. The age of onset of the occlusive process is of prognostic importance, and in our patients the incidence of amputation increased sharply in disease beginning in the later decades of life (Fig. 2). Survival Rate.-During the period of observation 88 patients died. The overall mortality rate was 21%, with an average survival of eight years below the age of 50 and of four years above that age. Atherosclerosis is a generalized disease, and it is not surprising that coronary occlusion accounted for 40% of the deaths. The incidence of fatal cerebrovascular accidents (11%) was, however, lower than in other series.Associated Diseases.-Hypertension (systolic B.P. over 180 mm. Hg) was present in 114 (28%/o) patients. It is of interest to note that the limb-amputation rate in these patients was only 5% as compared with the overall incidence of 10%. Coronary disease, as evidenced clinically by angina of effort, was present in 71 (17%) patients. This latter figure is surprisingly low, as is also the incidence of diabetics, who numbered only 18 (4.50/ ).

We measured soluble intercellular adhesion molecule-1 (sICAM-1) in the serum and cerebrospinal fluid (CSF) of 35 clinically active relapsing-remitting (RR) multiple sclerosis (MS) patients who underwent both lumbar puncture and gadopentetate dimeglumine (Gd-DTPA)-enhanced MRI within an interval of 1 week, and of 30 neurological controls of whom 17 had noninflammatory neurologic diseases (NIND), 8 bacterial meningitis (BM), and 5 AIDS dementia complex (ADC). Thirteen of the MS patients assumed corticosteroids at the time of the study. While sICAM-1 serum levels were highest in the BM group (p < 0.005), untreated MS patients showed levels higher (p < 0.05) than treated MS and NIND, but similar to ADC. Moreover, the untreated MS group had CSF/serum sICAM-1:CSF/serum albumin (sICAM-1 index) values higher than the treated group (p < 0.01), NIND (p < 0.005), and BM (p < 0.05); high sICAM-1 index was found also in ADC. Untreated MS patients with one or more Gd-DTPA-enhancing MRI lesions (Gd-positive) had higher mean values of CSF/serum albumin ratio (QAlbumin) and CSF mononuclear cells compared to patients without such lesions (Gd-negative). In the untreated Gd-negative patients, sICAM-1 serum levels were higher (p < 0.05) than those in Gd-positive patients. In the latter group, there were positive correlations between the number of CSF mononuclear cells and both IgG (p < 0.01) and sICAM-1 indices (p < 0.05), between QAlbumin and QsICAM-1 (p < 0.005) and between Qalbumin and the Expanded Disability Status Scale score (p = 0.05). There were no significant correlations in the Gd-negative group. These results suggest that sICAM-1 index can be a better marker of intrathecal sICAM-1 synthesis than CSF levels and provide additional insights, in vivo, into the blood-brain barrier mechanisms underlying MRI Gd-enhancement in clinically active RR MS.

In this study, we evaluated the effect of a 2 -adrenoceptor activation on catecholamine release from the adrenal medulla of pre-hypertensive (6-week-old) and hypertensive (16-week-old) spontaneously hypertensive rats (SHR) and of agematched normotensive control Wistar Kyoto (WKY) rats. Catecholamine overflow from isolated adrenal medullae was evoked by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) in the absence and presence of the a 2 -adrenoceptor agonist medetomidine (MED). The spontaneous outflow of adrenaline was similar between age-matched SHR and WKY rats. However, the spontaneous outflow of noradrenaline was significantly lower in SHR compared with agematched WKY rats. DMPP (0.1-3 mM) increased the outflow of noradrenaline and adrenaline in a concentration-dependent manner. The E max values for adrenaline overflow were similar between strains, but the E max values for noradrenaline overflow were significantly lower in SHR. The EC 50 values for noradrenaline and adrenaline overflow were significantly higher in SHR compared with age-matched WKY rats. MED (0.1-300 nM) reduced the DMPP-evoked overflow (DMPP 500 lM) of noradrenaline and adrenaline in a concentration-dependent manner and was capable of totally inhibiting this effect. The inhibitory action of MED was similar between age-matched SHR and WKY rats. In the adrenals, the a 2A -and a 2B -adrenoceptor subtypes had the highest mRNA expression levels; the a 2C -adrenoceptor subtype had the lowest mRNA expression levels. The mRNA levels for the three subtypes were similar between strains. In conclusion, in SHR during the development of hypertension, adrenal a 2 -adrenoceptor inhibitory function is conserved, accompanied by reduced noradrenaline release and unchanged adrenaline release. a 2 -Adrenoceptors are important target molecules for endogenous catecholamines and exogenous pharmacological agents. a 2 -Adrenoceptors consist of three genetically distinct subtypes, a 2A , a 2B and a 2C [1]. Presynaptic a 2 -adrenoceptors play a critical role in regulating noradrenaline release from sympathetic nerve terminals by a negative feedback mechanism [2,3]. Moreover, a 2 -adrenoceptors are solely responsible for autocrine feedback inhibition of noradrenaline and adrenaline secretion from the adrenal medulla [4][5][6][7].Increased activity of the sympathetic nervous system (SNS) accompanied by increased noradrenaline spillover has been implicated in the pathogenesis of essential hypertension in humans [8][9][10] and in an animal model of this disorder, the spontaneous hypertensive rat (SHR) [11,12]. Impairment of presynaptic a 2 -adrenoceptors by a reduced expression of the a 2A -adrenoceptor subtype has been associated with the increased noradrenaline release that is associated with the hypertensive phenotype in SHR [13,14].The adrenal medulla in combination with the SNS also plays a role in the epigenesis of hypertension in SHR. Hypertension and left ventricular hypertrophy were absent only in sympathectomized SHR tha...

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