Sulfasalazine-induced Angioimmunoblastic lymphadenopathy developing in a patient with juvenile chronic arthritis

We describe a patient with juvenile chronic arthritis who developed reactive angioimmunoblastic lymphadenopathy, induced by sulfasalazine. Development of angioimmunoblastic lymphadenopathy although rare, is a very serious side effect of sulfasalazine treatment, and patients treated with this drug should be watched carefully. Received: 10 April 2000 / Accepted: 16 June 2000     

Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome

Membrane cofactor protein (MCP; CD46) is a widely expressed transmembrane complement regulator. Like factor H it inhibits complement activation by regulating C3b deposition on targets. Factor H mutations occur in 10-20% of patients with hemolytic uremic syndrome (HUS). We hypothesized that MCP mutations could predispose to HUS, and we sequenced MCP coding exons in affected individuals from 30 families. MCP mutations were detected in affected individuals of three families: a deletion of two amino acids (D237/S238) in family 1 (heterozygous) and a substitution, S206P, in families 2 (heterozygous) and 3 (homozygous). We evaluated protein expression and function in peripheral blood mononuclear cells from these individuals. An individual with the D237/S238 deletion had reduced MCP levels and approximately 50% C3b binding compared with normal controls. Individuals with the S206P change expressed normal quantities of protein, but demonstrated approximately 50% reduction in C3b binding in heterozygotes and complete lack of C3b binding in homozygotes. MCP expression and function was evaluated in transfectants reproducing these mutations. The deletion mutant was retained intracellularly. S206P protein was expressed on the cell surface but had a reduced ability to prevent complement activation, consistent with its reduced C3b binding and cofactor activity. This study presents further evidence that complement dysregulation predisposes to development of thrombotic microangiopathy and that screening patients for such defects could provide informed treatment strategies.     

Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample

Attention deficit hyperactivity disorder (ADHD) is a highly heritable and heterogeneous disorder, which usually becomes apparent during the first few years of childhood. Imbalance in dopamine neurotransmission has been suggested as a factor predisposing to ADHD. However, evidence has suggested an interaction between dopamine and serotonin systems in the pathophysiology of the disorder. Studies using selective agonists of the different 5-HT receptors microinjected into selected brain structures have shown a positive modulating effect on the functional activities of the mesotelencephalic dopaminergic system. This suggests that some of the genetic predisposition to ADHD might be due to DNA variation at serotonin system genes. In this study, we investigated polymorphisms in HTR(1B) and HTR(2A) (which encode the serotonin receptors 5-HT(1B) and 5-HT(2A) respectively) in a European ADHD sample. Using haplotype based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) analyses, we observed significant preferential transmission of the allele 861G of the HTR(1B) in the total sample (for HHRR; chi(2) = 7.4, P = 0.0065 and TDT; (chi(2) = 6.4, P = 0.014). Analysis of HTR(2A) failed to reveal evidence of association or linkage between the His452Tyr polymorphism and ADHD in the total sample. However, a significantly increased transmission of the allele 452His was observed in the Irish sample alone (chi(2) = 4.9, P = 0.026). These preliminary data suggest an important role for the serotonin system in the development of ADHD. Further studies, preferentially including different ethnic groups are required to substantiate these findings.     

Visual hallucinations induced by the combination of prolintane and diphenhydramine

The case of a young man is presented who developed visual hallucinations following two months of concomitant use of prolintane and diphenhydramine at therapeutic dosages. An increase in dopaminergic brain activity is proposed as the causal mechanism for hallucinations--whereas prolintane can induce the release of dopamine at the synaptic cleft, diphenhydramine can act inhibiting the reuptake of dopamine and inducing a potentiation of its effects. The psychiatric complications appearing two months after starting the use of both drugs could be attributed to a phenomenon of pharmacological kindling.     

Bone sialoprotein-induced reparative dentinogenesis in the pulp of rat’s molar

Bone sialoprotein (BSP), an osteogenic protein (OP), mixed with a carrier, was implanted in the pulp of rat first upper molars (OP group). Cavities were prepared with dental burs and pulp perforation was carried out by pressure with the tip of a steel probe. After 8, 14, and 30 days, the rats were killed and the pulps of the OP group were compared with (1) a sham group (S group), (2) a group where the carrier was implanted alone (C group), and (3) capping with calcium hydroxide (Ca group). After 8 days, a few inflammatory cells were seen, mostly located at the pulp surface near the perforation. In the Ca group, a dentin bridge started to form, in contrast to the other groups. After 15 days, globular structures were seen in the pulps of the S and C groups. A reparative osteodentin bridge isolated the pulp from the cavity in the Ca group. Variable reactions were seen in the OP group, with some evidence of cell and matrix alignments or plugs of osteodentin in continuity with an inner layer of reparative dentin. After 30 days, irregular osteodentin formation was observed in the pulps of the S and C groups, with a tendency for globular structures to merge, but with interglobular spaces filled by pulp remnants. In the Ca group, osteodentin was observed in the mesial part of the pulp chamber. In the BSP-implanted group, the osteogenic protein stimulated the formation of a homogeneous dentin-like deposit occupying most of the mesial part of the pulp. Apparently, BSP stimulates the differentiation of cells which secrete an organized extracellular matrix more efficiently than any other capping material used so far. Altogether, the results reported here support that bone sialoprotein displays novel bioactive properties and is capable of stimulating in 1 month’s time the development of a thick reparative dentinal tissue in the pulp, occluding the perforation and filling the mesial third of the pulp chamber. Received: 13 October 1999 / Accepted: 6 December 1999     

Cholelithiasis in cervico-oculo-acoustic (Wildervanck's) syndrome

An unusual case of cholelithiasis in an 18–month-old boy with cervico-oculo-acoustic (Wildervanck's) syndrome is presented. Our patient had Duane's retraction syndrome, Klippel-Feil anomaly and congenital deafness. To our knowledge this is the first case in which a probable association between cholelithiasis and Wildervanck's syndrome has been recorded. On the other hand, the presence of mutual malformations and anomalies such as scoliosis, ventricular septal defect, ectopic kidney, hydrocephalus, hypoplastic thumb and growth retardation seems to suggest that Wildervanck's syndrome is a clinical variant of Klippel-Feil sequence.     

Magnetic resonance imaging and contrast CT of the lumbar spine. Comparison of diagnostic methods and correlation with surgical findings

Thirty-two patients with suspected lumbar disc herniation were studied with magnetic resonance imaging (MRI) and contrast computed tomography (CT). One hundred disc levels were evaluated. Twenty-five patients underwent surgery on 31 discs, allowing anatomic confirmation of the diagnosis. Surgical findings supported the MRI diagnosis at 28 of 31 levels (90.3% accuracy), whereas the CT diagnosis correctly reflected only 24 of 31 levels (77.4% accuracy). Discrepancy between MRI and CT interpretation occurred at ten levels that were surgically explored. Computed tomography (CT) was incorrect at seven levels, and MRI was in error at three levels. The sensitivity of MRI was 91.7%, compared with 83.3% for CT, and the MRI specificity of 100% was superior to 71.4% for CT. This study demonstrates the clinical superiority of surface coil MRI over contrast CT in the evaluation of lumbar disc herniation. Surface coil MRI can be used as the initial diagnostic procedure for a suspected herniated lumbar disc, using invasive contrast studies and CT, if required, to clarify an equivocal MRI finding.     

Autosomal dominant periodic fever with AA amyloidosis: tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Turkish family

We investigated the presence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a Turkish family with recurrent fever and systemic reactive (AA) amyloidosis. A missense mutation in exon 3 of the TNFRSF1A gene, resulting in an amino acid substitution Phe60Leu (F60L) was found in the proband and his father. These are the first confirmed TRAPS cases in the Turkish population. This family highlights the importance of onsidering all the causes of inherited fevers and performing thorough clinical and genetic investigations to secure a diagnosis, even in populations in which familial Mediterranean fever (FMF) is highly prevalent.