Objective. To describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE).Methods. Cases of juvenile SLE-associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve.Results. The study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thromDr Pringe is recipient of an Alpha Scholarship from the European Union (contract no. AML/B7-311/970666/II-0246-FI).

Objectives: To differentiate onset of CNS involvement in primary hemophagocytic lymphohistiocytosis (HLH) from that of other CNS inflammatory diseases and to identify early symptoms linked to abnormal cognitive outcome.Methods: Forty-six children with primary HLH who had neurologic evaluation within 2 weeks and brain MRI within 6 months of diagnosis were included. Initial symptoms, CSF study, brain MRI, and neurologic outcome were assessed. Brain MRIs were compared with those of 44 children with acute disseminated encephalomyelitis (ADEM).Results: At disease onset, 29 children (63%) had neurologic symptoms and 7 (15%) had microcephaly. Twenty-three (50%) children had abnormal CSF study, but only 15 (33%) had abnormal brain MRI. The latter showed that patients with HLH, unlike patients with ADEM, had symmetric periventricular lesions, without thalamic and brainstem involvement and with infrequent hyposignal intensity on T1. At the end of follow-up (3.6 Ϯ 3.6 years), 17 of the 28 (61%) surviving patients had normal neurologic status, 5 (18%) had a severe neurologic outcome, and 6 (21%) had mild cognitive difficulties. Abnormal neurologic outcome was not influenced by age or type of genetic defect, but by the presence of neurologic symptoms, MRI lesions, or abnormal CSF study at onset. Early clinical and MRI symptoms may regress after treatment.Conclusion: Neurologic symptoms are frequent at the onset of primary HLH and are mostly associated with abnormal CSF findings, but with normal brain MRI. In cases of abnormal brain MRI, the observed lesions differ from those of ADEM. Neurology ® 2012;78:1150-1156 GLOSSARY ADEM ϭ acute disseminated encephalomyelitis; CHS ϭ Chediak-Higashi syndrome; CRF ϭ case report form; FHLH ϭ familial hemophagocytic lymphohistiocytosis; FLAIR ϭ fluid-attenuated inversion recovery; GS ϭ Griscelli syndrome; HLH ϭ hemophagocytic lymphohistiocytosis; HPS ϭ Hermansky-Pudlak syndrome; HSCT ϭ hematopoietic stem cell transplantation; MTX ϭ methotrexate; PID ϭ primary immunodeficiencies; SE ϭ spin-echo; WI ϭ weighted image; XLP ϭ X-linked lymphoproliferative syndrome.

Seventy-four patients with β-thalassemia major were studied to test the hypothesis that a deficiency of protein C (PC) and antithrombin III (AT III), both antithrombotic proteins, could contribute to the pathogenesis of CNS thromboembolic lesions. In 70 patients, PC levels were found to be significantly lower than normal, whereas AT III activity was found to be lower only in 41 patients. The lowest values of PC and AT III were found in older splenectomized patients, a low PC value only was found in chronic hepatitis patients. Prothrombin time and fibrinogen were found to be particularly abnormal in patients with chronic hepatitis and without spleen. A relatively poor correlation was observed between PC and AT III (p < 0.02). PC correlated with age (p < 0.001), transfusional iron (p < 0.001) and ferritin (p < 0.001). It also correlated with serum albumin (p < 0.001), prothrombin time (p < 0.001) and fibrinogen (p < 0.02) and with serum transaminases (GPT) (p < 0.001). The same indexes correlated less significantly with AT III activity. Nevertheless, only 2 of our patients had CNS thromboembolic complications. It is probable that low clotting factors, hyperfibrinolysis and thrombocytopenia (which are common in chronic liver disease) could have the opposite effect on hemostasis from that of low levels of anticoagulant proteins such as PC and AT III.

pK values have been determined, in 20% (by weight) dioxan, for aromatic monocarboxylic acids derived from naphthalene, l-methylnaphthalene, 1,s-dimethylnaphthalene, and acenaphthene. Both the pK values and the ultraviolet spectral data are in accord with the order of increasing steric effect: ethylene bridge < 1-methyl < 1,8-dimethyl.ACENAPHTHENE, l-methylnaphthalene, and 1,8-dimethylnaphthalene form a series in which the steric and electronic effects of the alkyl substituents are expected to fall into different sequences. Information on these substituent effects should be given by the dissociation constants of the derived carboxylic acids and we report thermodynamic pK values for the three acenaphthoic acids, the three 1,8-dirnethylnaphthoic acids, and l-methyl-2-, 4-methyl-2-, 4-methyl-l-, and 5-methyl-l-naphthoic acid. Relevant ultraviolet spectral data are also reported. EXPERIMENTALMicroanalyses were carried out by the Microanalytical Laboratory (Dr. A. D. Campbell) of the University of Otago.Methylnaphthoic Acids.-(a) 1-Methyl-2-naphthoic acid. To a stirred suspension of 2-dimethylaminomethyl-l-methylnaphthalene (5.0 g. ; b. p. 118-122"/1 mm.) in water (150 ml.) was added (3 hr.) finely powdered potassium permanganate (10.0 g.). The mixture was stirred for a further 2 hr. and the manganese dioxide formed was filtered off. Acidification of the filtrate afforded the required acid (2-1 g., 45%), m. p. 179-5-180".was used for the oxidation, lower yields of the acid were

Product distributions resulting from nitration of polymethylbenzenes in nitric acid-acetic anhydride mixtures have been determined by gas chromatography. Nitration of a methyl group occurs in all the substrates studied; such nitration occurs only at a methyl group para to the methyl most activated to ipso nitration. These results support the view that side chain nitration occurs through the diene intermediates which lead to ring acetoxylation.