Refractory increased intracranial pressure in severe traumatic brain injury: barbiturate coma and bispectral index monitoring

Patients with severe traumatic brain injury resulting in increased intracranial pressure refractory to first-tier interventions challenge the critical care team. After exhausting these initial interventions, critical care practitioners may utilize barbiturate-induced coma in an attempt to reduce the intracranial pressure. Titrating appropriate levels of barbiturate is imperative. Underdosing the drug may fail to control the intracranial pressure, whereas overdosing may lead to untoward effects such as hypotension and cardiac compromise. Monitoring for a therapeutic level of barbiturate coma includes targeting drug levels and using continuous electroencephalogram monitoring, considered the gold standard. New technology, the Bispectral Index monitor, utilizes electroencephalogram principles to monitor the level of sedation and hypnosis in the critical care environment. This technology is now being considered for targeting appropriate levels of barbiturate coma.     

A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection

The toll-like receptor 2 (TLR2) has gained importance as a major mammalian receptor for lipoproteins derived from the cell wall of a variety of bacteria, such as Borrelia burgdorferi, Treponema pallidum, and Mycoplasma fermentans. We were interested in identifying mutations in the TLR2 gene that might prove to be associated with altered susceptibility to septic shock. We performed a mutation screen of the TLR2 gene using single-stranded conformational polymorphism in 110 normal, healthy study subjects and detected an Arg753Gln mutation in three individuals. No other missense mutations were detected in the TLR2 open reading frame. Functional studies demonstrate that the Arg753Gln polymorphism, in comparison to the wild-type TLR2 gene, is significantly less responsive to bacterial peptides derived from B. burgdorferi and T. pallidum. In a septic shock population, the Arg753Gln TLR2 polymorphism occurred in 2 out of 91 septic patients. More importantly, both of the subjects with the TLR2 Arg753Gln polymorphism had staphylococcal infections. These findings suggest that a mutation in the TLR2 gene may predispose individuals to life-threatening bacterial infections.     

Recurrent trisomy 21: four cases in three generations

Recurrent trisomy 21: four cases in three generations.While gonadal mosaicism can lead to recurrence of trisomy 21 (T21) for a single couple, the recurrence of free T21 in multiple members of a single pedigree has rarely been reported. We present an unusual pedigree with four cases of Down syndrome (DS) with free T21 were born to four separate women related through three generations of one family. The mothers were aged 18, 21, 29, and approximately 30 years at the time of the births. Using microsatellite markers, we excluded most of chromosome 21, excepting two small regions within 21q11.1 and 21q22.3, as being shared among the mothers of the DS children. However, two members of the pedigree, including one DS mother with a normal G-banded karyotype, carried supernumerary alleles at markers 2503J9TG, D21S369, and D21S215, which span the region from 21pter to 21q11.1. Fluorescence in situ hybridization using a centromeric probe hybridizing to chromosomes 13 and 21 did not reveal a novel location, ruling out a cryptic centromeric translocation between chromosome 21 and any chromosome other than chromosome 13. The level of meiotic recombination on chromosome 21 was unusually high in this family as well. We hypothesize that a cryptic rearrangement within the highly repetitive region of 21q11.1 is present in this family, disrupting pairing and leading to an increased risk of non-disjunction of chromosome 21 in this family.     

Characterization and Comparison of the Human and Mouse GLC1A Glaucoma Genes

The GLC1A gene (which encodes the protein myocilin) has been associated with the development of primary open angle glaucoma. Bacterial artificial chromosomes containing the human GLC1A gene and its mouse ortholog were subcloned and sequenced to reveal the genomic structure of the genes. Comparison of the coding sequences of the human and mouse GLC1A genes revealed a high degree of amino acid homology (82%) and the presence of several conserved motifs in the predicted GLC1A proteins. The expression of GLC1A was examined by Northern blot analysis of RNA from adult human tissues. GLC1A expression was observed in 17 of 23 tissues tested, suggesting a wider range of expression than was recognized previously. The comparison of the human and mouse GLC1A genes suggests that the mouse may be a useful model organism in studying the molecular pathophysiology of glaucoma.     

Prenatally detected trisomy 20 mosaicism

BACKGROUND: Trisomy 20 is one of the more common mosaic trisomies detected on amniocentesis and presents with a normal outcome in over 90% of reported cases. Trisomic cells are almost never confirmed in newborn blood and are only rarely found in other fetal or placental samples. Nonetheless, some abnormal outcomes have been reported, including unexplained fetal demise, intrauterine growth restriction, and multiple congenital anomalies. Because of the lack of molecular studies on such cases, it is unknown whether the origin of trisomy or presence of uniparental disomy (UPD) could have some influence on outcome. METHODS: We present data on six cases of trisomy mosaicism, two detected by chorionic villous sampling (CVS) and four by amniocentesis (AF), submitted to our laboratory for molecular studies. RESULTS AND CONCLUSIONS: A meiotic origin of the trisomy could be confirmed in only one of these cases. In addition, uniparental disomy was excluded in all four cases for which parents were available for testing. The four cases with low levels of trisomy in amniotic fluid (0%, 10%, 11%, and 12%) were associated with a normal outcome. The remaining two cases of trisomy 20 had high levels of trisomy in amniotic fluid (96% and 58%) and had abnormal outcomes (developmental delay in one and stillbirth with IUGR and severe oligohydramnios in the other). Including previously published cases, there is a clear association with the level of trisomy and outcome, with only 4% abnormal outcomes when <40% trisomic cells were detected. Higher levels of trisomy were also observed in male fetuses as compared to female fetuses (p = 0.01); however, there were no sex differences in frequency of abnormal outcomes.     

Sclerosing inflammatory pseudotumor of the eye

We report the clinical course and pathologic findings in a case of intraocular sclerosing inflammatory pseudotumor in a 21-year-old man. The patient initially had a unilateral right interstitial keratitis, scleritis, uveitis, ciliary body mass, and retinal detachment. Scleral and vitreous biopsy specimens revealed an inflammatory process. The eye was eventually enucleated despite therapy with high doses of prednisone and ciprofloxacin hydrochloride. Histologic examination of the globe showed nongranulomatous, acute (neutrophils) and chronic (lymphocytes and histiocytes) inflammation with proliferation of fibrous tissue within the vitreous cavity, uvea, sclera, and contiguous orbital fibroadipose tissue. The contralateral eye later developed a similar mass that resolved following aggressive and prolonged immunosuppressive therapy with retention of 20/16 visual acuity.