A convenient synthesis of [11C]paraquat and other [N‐methyl‐11C]bisquaternary ammonium compounds

[¹¹C]Paraquat was synthesized by the reaction of [¹¹C]methyl triflate with the mono‐triflate salt of 1‐methyl‐[4,4′]bipyridinyl. The product was selectively separated from the precursor by a microcolumn of Chelex 100 ion exchange resin. The method was applied to the synthesis of a variety of [N‐methyl‐¹¹C]bisquaternary ammonium compounds. This is the first reported use of a chelating cation exchange resin for the selective purification of organic dications. Copyright © 2002 John Wiley & Sons, Ltd.     

Positron emission tomography for the early postsurgical evaluation of pediatric brain tumors

Object The object was to study the value of postoperative positron emission tomography (PET) to assess the extension of brain tumor resection.Methods Twenty children operated on for total resection of a glial tumor (18 low-grade, 2 anaplastic) presented a signal on postoperative magnetic resonance (MR) images raising the question of a possible tumor residue. PET was performed early (¹⁸F-Fluoro-deoxyglucose in 1, ¹¹C-methionine in 16, both in 3) to further characterize the nature of the abnormal MR signal in order to consider second-look surgery. An increased tracer uptake found in 14 children led to reoperation on 11 of them, confirming the tumor histologically. No ¹¹C-methionine uptake led to a conservative attitude in 6 children in whom MR imaging follow-up showed no tumor progression.Conclusions The early postoperative PET, especially with ¹¹C-methionine, appears to be a valid basis for complementary therapeutic decisions, especially second-look surgery, in glial tumors for which a radical resection is a key factor for prognosis.     

Increased basal ganglia volumes in velo-cardio-facial syndrome (deletion 22q11.2).

BACKGROUND: This study evaluated differences in caudate volumes in subjects with velo-cardio-facial syndrome due to a 22q11.2 (22qDS) deletion. Because psychosis is observed in 30% of adult subjects with 22qDS, this neurogenetic disorder could represent a putative model for a genetically mediated subtype of schizophrenia.METHODS: Caudate volumes were measured on high-resolution magnetic resonance images in 30 children and adolescents with 22qDS and 30 gender- and age-matched normal comparison subjects.RESULTS: Caudate head volumes were increased in the 22qDS group independent of neuroleptic medications. Subjects with 22qDS also displayed an abnormal pattern of asymmetry in the anterior caudate, with left side greater than right.CONCLUSIONS: Alterations in the basal ganglia circuitry have been implicated in learning, cognitive, and behavioral problems in children and therefore could be involved in the expression of the neurobehavioral phenotype expressed by subjects with 22qDS. Abnormal caudate volume is a neurodevelopmental feature shared with schizophrenia, further establishing 22qDS as a potential neurodevelopmental model for this disorder.     

Analysis of the variability of CMV strains in the RL11D domain of the RL11 multigene family

Human cytomegalovirus (CMV) contains one of the largest genomes within the herpesvirus family and includes 12 multigene families. One of these is the RL11 family, whose members encode a characteristic domain, called RL11D. In the present study, the sequence variability of RL11D within the UL1, UL4, UL6, UL7, and UL10 genes of the RL11 family was investigated. For this purpose, these genes were analyzed in 70 clinical isolates obtained from urine, bronchoalveolar lavage, and blood of different patients. Substantial genetic variability among the clinical isolates was observed in all five genes analyzed. Based on phylogenetic analysis of variations in RL11D, the clinical isolates could be classified into three genotypes for UL1, 7, and 10 and, four genotypes for UL4 and 6. Further analysis showed statistically significant linkages between the following pairs of genes: UL6/UL7, UL4/UL7, UL1/UL4, and UL4/UL6. The data show that CMV strains exhibit a high interstrain variability in the RL11D domain of various RL11 family genes. Sequence variations, however, can be clearly grouped into a limited number of distinct genotypes. The genetic linkages found probably reflect a low frequency of recombination between genes that are arranged in close proximity on the viral genome.     

Prenatal diagnosis of mosaicism for 11q terminal deletion

The phenotype of 11q terminal deletion also known as Jacobsen syndrome is a clinically well known entity whose diagnosis in infancy and childhood is based on clinical examination, hematological and cytogenetic findings. Hematological features in Jacobsen syndrome are very similar to those reported in Paris–Trousseau syndrome (PTS) which is also associated with11q terminal deletion. Karyotype analysis shows a variable terminal deletion from 11q23 sub-band extending to the telomere. Most often in patients with Jacobsen syndrome, this chromosomal deletion is present in all metaphases. We report on the identification of a distal 11q deletion in mosaic (20% of deleted cells) in a fetus ascertained after amniocentesis for maternal serum screening test indicative for Down syndrome. The present case is the third prenatal diagnosis of a mosaic for a distal 11q deletion with the lowest mosaicism rate. The 2D-ultrasound examination and cord blood hematological studies were useful to estimate the prognosis at term, considering the contribution of the mosaicism rate to the phenotypic variability in Jacobsen syndrome. The identification of mosaicism for distal 11q deletion is a very rare event in prenatal diagnosis. This case illustrates the complexity in genetic counselling for prenatally ascertained partial monosomy 11qter in mosaic.     

The cellular Mre11 protein interferes with adenovirus E4 mutant DNA replication

Adenovirus type 5 (Ad5) relocalizes and degrades the host DNA repair protein Mre11, and efficiently initiates viral DNA replication. Mre11 associates with Ad E4 mutant DNA replication centers and is important for concatenating viral genomes. We have investigated the role of Mre11 in the E4 mutant DNA replication defect. RNAi-mediated knockdown of Mre11 dramatically rescues E4 mutant DNA replication in cells that do or do not concatenate viral genomes, suggesting that Mre11 inhibits DNA replication independent of genome concatenation. The mediator of DNA damage checkpoint 1 (Mdc1) protein is involved in recruiting and sustaining Mre11 at sites of DNA damage following ionizing radiation. We observe foci formation by Mdc1 in response to viral infection, indicating that this damage response protein is activated. However, knockdown of Mdc1 does not prevent Mre11 from localizing at viral DNA replication foci or rescue E4 mutant DNA replication. Our results are consistent with a model in which Mre11 interferes with DNA replication when it is localized at viral DNA replication foci.     

Etiological theories and treatments for chronic back pain. I. Somatic models and interventions

This is the first part of an extended review of the etiology and treatment of chronic back pain (CBP). This paper will address the pathophysiology of CBP, the somatic conceptualizations that have been developed, and the treatment modalities that have been employed to alleviate the symptoms. The adequacy of the different models and treatments will be critically examined. The second paper in this set will examine psychological models and interventions. Common problems to both somatic and psychological approaches will be discussed at the close of the second paper.     

Recurrent hypocalcemic tetany, generalized seizures and increased bronchopulmonary infections in an 18-year-old patient

Zusammenfassung Ein 18-j?hriger Patient wurde wegen eines generalisierten Anfalls station?r eingewiesen. In der Vorgeschichte traten seit der Kindheit rezidivierende hypokalz?mische Tetanien und insgesamt 3 generalisierte Anf?lle auf. Ebenfalls waren anamnestisch geh?ufte Atemwegsinfektionen eruierbar. Auff?llig waren pathologische Befunde des Kalziumhaushaltes mit einer Hypokalz?mie und einem Hypoparathyreoidismus sowie ein gest?rtes zellul?res Immunsystem mit einer selektiven Verminderung sowie einem Funktionsdefizit der T-Helferzellen. Unter der Verdachtsdiagnose eines kombinierten famili?ren Fehlbildungssyndroms der Nebenschilddrüsen und des Thymus wurde eine Fluoreszenz-in-situ-Hybridisierung durchgeführt, in der eine heterozygote Mikrodeletion im Bereich des Chromosoms 22q11 gesichert werden konnte. Als Diagnose wurde ein DiGeorge-Syndrom erhoben, das eine der m?glichen klinischen Manifestation im Rahmen eines Chromosom-22q11-Deletionssyndroms darstellt. Es handelt sich um eine angeborene Fehlbildungsst?rung der 3. und 4. Schlundtasche, bei der Patienten mit abortiven Formen das Erwachsenenalter erreichen k?nnen. Unter einer dauerhaften Kalzium- und Vitamin-D-Substitutionstherapie blieb der Patient bei normalisierten Kalziumwerten beschwerde- und anfallsfrei.