Multicentric Castleman disease in an HHV-8-infected child born to consanguineous parents

Childhood multicentric Castleman disease (MCD) is a rare and unexplained lymphoproliferative disorder. We report a human herpesvirus-8 (HHV-8)-infected child, born to consanguineous Comorian parents, who displayed isolated MCD in the absence of any known immunodeficiency. We also systematically review the clinical features of the 32 children previously reported with isolated and unexplained MCD. The characteristics of this patient and the geographic areas of origin of most previous cases suggest that pediatric MCD is associated with HHV-8 infection. Moreover, as previously suggested for Kaposi sarcoma, MCD in childhood may result from inborn errors of immunity to HHV-8 infection.     

Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections

Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to specific human papillomaviruses, the betapapillomaviruses. These EV-HPVs cause warts and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most, but not all, patients with autosomal recessive EV. We found that 2 young adult siblings presenting with T cell deficiency and various infectious diseases, including persistent EV-HPV infections, were homozygous for a mutation creating a stop codon in the ras homolog gene family member H (RHOH) gene. RHOH encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells. Patients' circulating T cells contained predominantly effector memory T cells, which displayed impaired TCR signaling. Additionally, very few circulating T cells expressed the β7 integrin subunit, which homes T cells to specific tissues. Similarly, Rhoh-null mice exhibited a severe overall T cell defect and abnormally small numbers of circulating β7-positive cells. Expression of the WT, but not of the mutated RHOH, allele in Rhoh-/- hematopoietic stem cells corrected the T cell lymphopenia in mice after bone marrow transplantation. We conclude that RHOH deficiency leads to T cell defects and persistent EV-HPV infections, suggesting that T cells play a role in the pathogenesis of chronic EV-HPV infections.     

Further study on the specificity and incidence of neutralizing antibodies to interferon (IFN) in relapsing remitting multiple sclerosis patients treated with IFN beta-1a or IFN beta-1b.

The development of neutralizing antibodies (NAbs) to interferon (IFN) is a common phenomenon of IFN beta therapy for relapsing-remitting multiple sclerosis (RRMS) patients. Here we examine the specificity of NAbs developed during therapy for RRMS with recombinant interferon (rIFN) beta-1a or rIFN beta-1b, and study the effect of switching from rIFN beta-1a to rIFN beta-1b on the incidence and specificity of NAbs. The relative ability to neutralize rIFN beta-1a and beta-1b was assayed in sera positive for NAbs derived from RRMS patients treated with either rIFN beta-1a (N=9) or rIFN beta-1b (N=16), while the incidence and specificity of NAbs to IFN beta developed during therapy were studied in 50 RRMS patients who were treated for two years with rIFN beta-1a followed by a further year either switching to rIFN beta-1b (N=34) or continuing treatment with rIFN beta-1a (N=16). The results show that all positive sera, independent of the source, may recognize both forms of rIFN beta and that a further year of treatment does not significantly affect the incidence and specificity of the NAbs developed during the first two years of treatment even if treatment is switched to a different type of IFN beta. The data then suggests that it is unlikely that the administration of rIFN beta-1b to anti-rIFN beta-1a NAbs-positive patients can overcome the inhibitory effect exerted by the serum antibodies (and vice versa), and that a further period of treatment with IFN beta-1b in patients previously treated with rIFN beta-1a does not significantly change the pattern of antibody response to IFN beta.     

Expert systems for medical consultation.

After reviewing some of the elements that permit a clearer understanding of what characterizes the "expert systems" approach, representation of medical concepts, symbolic manipulation rather than numeric calculation, causal reasoning, etc., this paper will try to deal with some of the most noteworthy developments in medical decision aid, teaching, research, before discussing some problems raised by the evaluation of expert systems in medicine.     

Comparison of cerebral angiography and transcranial Doppler sonography in acute stroke

We compared digital intra-arterial angiography and transcranial Doppler sonography in acute cerebral ischemia as part of a wider study on a continuous series of 48 patients with acute focal cerebral ischemia in the carotid territory, observed within 4 hours of the onset of symptoms. The most significant Doppler findings of the middle cerebral artery included no detection of the artery when occlusion of the carotid siphon or the middle cerebral artery at its origin was shown by angiography and reduced flow velocities and asymmetry (symptomatic less than asymptomatic) when the occlusion was located in the terminal tract of the middle cerebral artery mainstem or in numerous terminal branches. Higher flow velocities in the anterior cerebral artery or posterior cerebral artery, mostly in the symptomatic hemisphere, often accompanied middle cerebral artery pathology, probably indicating collateral compensatory pathways.     

Superior orbital fissure syndrome. Review of 130 cases.

Superior orbital fissure syndrome is a symptomatologic complex, consisting of retroorbital pain, paralysis of extraocular muscles, impairment of first trigeminal branches and frequent involvement of the optic nerve. From a review of 130 published cases including two personal observations, it appears that the clinical subdivisions and the several eponymic differentiations of this syndrome are unjustified on the basis of etiologic, therapeutic and prognostic elements. Only the presence--or absence--of optic signs may allow to hold the clinically useful distinction between the often 'benign' superior orbital fissure syndrome without optic nerve involvement, and the orbital apex syndrome where orbital exploration may be recommended. This review concludes that repeated neurosurgical and neuroradiologic investigations--with the exceptions of carotid angiography and orbital phlebography--can be avoided in such cases.