Cerebrovascular disease: evaluation with transbrachial intraarterial digital subtraction angiography using a 4-F catheter

Three hundred sixty-one patients underwent intraarterial digital subtraction angiography for definite or probable occlusive vascular disease of the carotid arteries. Examinations were performed with 65-cm-long, 4-F aortic catheters. A transbrachial approach was used. Images were good or excellent in nearly all cases. No postprocedural neurologic deficits or hematomas occurred. Permanent pulse deficit occurred in two patients, and temporary deficit occurred in three patients, an improvement over the frequency found in previous transbrachial series using 6-8-F catheters. While these results establish the efficacy of this technique, they also indicate a possible greater relative safety in men than in women.     

Effects of recombinant soluble type I interleukin-1 receptor on human inflammatory responses to endotoxin

Effects of soluble recombinant human type I interleukin-1 receptor (sIL- 1RI) were evaluated in 18 volunteers given intravenous endotoxin and randomized to placebo (n = 6), low-dose (n = 6), or high-dose (n = 6) sIL-1RI. Soluble IL-1RI decreased IL-1 beta (P = .001), but decreased IL-1ra (P = .0001), and resulted in 10-fold and 43-fold dose-related increases in sIL-1RI-IL-1ra complexes compared with placebo (P < or = .001). High-dose sIL-1RI was associated with increased levels of immunoactive tumor necrosis factor-alpha (P = .02), IL-8 (P = .0001), and cell-associated IL-1 beta (P = .047). C-reactive protein levels were higher after sIL-1RI than placebo (P = .035). Soluble IL-1RI decreased the severity of chills (P = .03), but did not alter other symptoms, changes in temperature, systemic hemodynamic responses, or changes in leukocyte and platelet number. Thus, sIL-1RI had no discernable antiinflammatory effect following endotoxin administration due in part to low levels of circulating IL-1 beta and neutralization of IL-1ra inhibitory function. This latter interaction represents an indirect mechanism of agonist activity elicited by sIL-1RI and may contribute to increases in inflammatory mediators, limiting therapy with sIL-1RI during endotoxemia.     

Parathyroid hormone resistance and B cell lymphopenia in propionic acidemia

The mechanisms of hypocalcemia, recurrent infections and hypogammaglobulinemia associated with metabolic decompensation of propionic acidemia due to propionyl-CoA carboxylase deficiency have not been defined. A 7-week-old infant with this disorder presented with severe hypocalcemia and B cell lymphopenia during an episode of metabolic acidosis and hyperammonemia. Hypocalcemia (1.1 mmoll ¹) was associated with elevated serum intact parathyroid hormone (122 ng 1 ¹), hyperphosphatemia, hypophosphaturia and hypercalcuria, indicating parathyroid hormone resistance. B cell lymphopenia (20 cells μl^-1) was associated with transient neutropenia, anemia and subsequent hypogammaglobulinemia (IgG < 294mgdl^-1, IgM < 8mgdl^-1, IgA < 8mgdl ¹), while T cells were normal. Parathyroid hormone resistance and B cell lymphopenia resolved following treatment with hemodialysis, diet and carnitine. These complications may be due to interference with parathyroid hormone renal tubular action and B cell maturation/proliferation by accumulated organic acids.     

Psychological mechanisms of enhanced risk of addiction in children of alcoholics: a dual pathway?

The background and rationale of a recently started project of the Amsterdam Institute for Addiction Research are outlined. This project is aimed at the psychological mechanisms underlying an enhanced risk of (later) addiction in children of alcoholics and the relationship with childhood psychopathology. A dual pathway mechanism is proposed, in which the type of alcoholism of the parent plays a major role. The child of a multigenerational primary alcoholic parent may suffer from an inherited mild dysfunction of the prefrontal cortex, expressed in neuropsychological and personality characteristics similar to those of the alcoholic parent. These are impulsive, aggressive and reward-seeking behaviour, response perseveration and, in some children, related psychopathology such as conduct disorders. For a child of a secondary alcoholic parent, another mechanism is proposed. In these children, stress and social learning may lead to negative affectivity and repressive coping style, with emotional problems at a later age, and the risk of falling into the "circle of secondary alcoholism". In both pathways, alcohol-related expectancies are suggested to constitute a "final common pathway" between different risk factors and later alcohol abuse. Specific expectancies might be related to different pathways and to gender differences in later drinking patterns.     

Mechanism of transient adsorption of fibrinogen from plasma to solid surfaces: role of the contact and fibrinolytic systems

The transient detection of fibrinogen on surfaces has been described (Vroman effect) and high-mol-wt kininogen (HK) has been shown to play a role in this reaction. In this study, we attempted to identify the form of HK responsible for preventing detection of the fibrinogen initially adsorbed from plasma to various artificial surfaces and to determine if other plasma components were involved. We compared 125I-fibrinogen adsorption in the presence of normal plasma to plasma deficient in specific proteins. On all surfaces tested, we found that fibrinogen was displaced from the surface. The extent of displacement was greatly reduced, however, but not eliminated in HK-deficient plasma. Factor XII- deficient plasma also showed reduced fibrinogen displacement. These data indicate that HK can actually displace fibrinogen; however, factor XII, or a factor XII-mediated reaction also appears to be necessary for this displacement to occur. Furthermore, when normal plasma was first subjected to extensive contact activation by dextran sulfate, during which the HK was extensively degraded to components smaller than the light chain (as assessed by Western blotting), we observed greatly reduced displacement of fibrinogen. Extensive contact activation of Factor XI-deficient plasma failed to show low-mol-wt derivatives, however, and displacement of fibrinogen was similar to normal plasma that had not undergone extensive activation. These data indicate that HKa (active cofactor produced during contact activation by factor XIIa or kallikrein) is primarily responsible for displacing fibrinogen, and that HKi (inactive cofactor generated by factor XIa) cannot displace fibrinogen. The fibrinogen from all plasma samples looked similar by Western blot analysis, suggesting that fibrinogenolysis was not a component of the Vroman effect. In addition, experiments performed with plasma prechromatographed on lysine agarose showed that a lysine- agarose adsorbable protein may be minimally involved in fibrinogen desorption and a synergism may exist between HK and that protein.