Acetabular labral tears of the hip in women

Acetabular labral tears are a major cause of hip dysfunction in young patients and a primary precursor to hip osteoarthritis. In addition, labral disease more commonly occurs in women and can present with nonspecific symptoms. It is possible to diagnose, quantify, and treat labral tears before the onset of secondary joint deterioration. However, the diagnosis requires a high index of suspicion, special attention to subtle patterns of presentation, and timely consideration for imaging studies. Treatment options are still evolving and include a wide array of nonsurgical and surgical techniques. Treatment should also address secondary dysfunction that can be associated with hip pathology. An initial trial of conservative management is recommended and failure to progress is an indication for surgical consultation.     

A 22-plex chemiluminescent microarray for pneumococcal antibodies

We developed a chemiluminescent multiplexed microarray that simultaneously determines IgG antibody concentrations to 22 pneumococcal polysaccharide (PnPs) serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 23F, and 33F). We compared the microarray with an enzyme-linked immunosorbent assay (ELISA) for 9 of the 22 serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F, and 23F). Correlation coefficients (r2) for the comparison of the microarray with ELISA ranged from 0.91 to 0.97 for the 9 serotypes. The microarray detected more than 4-fold increases in antibody concentrations in serum samples from before and 1 month after administration of pneumococcal vaccine for all 22 serotypes tested. The mean interassay and intra-assay coefficients of variation for 12 serum samples for the 22 serotypes were 7.6% and 6.0%, respectively. Inhibition-of-binding studies showed more than 90% inhibition by homologous serotypes and, with few exceptions, less than 25% inhibition by heterologous serotypes. The microarray multiplexing technology is an attractive alternative to ELISA for antibody responses to 23-valent PnPs vaccines.     

Progressive supranuclear palsy: pathology and genetics

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian disorder associated with progressive axial rigidity, vertical gaze palsy, dysarthria and dysphagia. Neuropathologically, the subthalamic nucleus and brainstem, especially the midbrain tectum and the superior cerebellar peduncle, show atrophy. The substantia nigra shows loss of pigment corresponding to nigrostriatal dopaminergic degeneration. Microscopic findings include neuronal loss, gliosis and neurofibrillary tangles in basal ganglia, diencephalon and brainstem. Characteristic tau pathology is also found in glia. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT) and recent studies have suggested that this may result in the altered expression of specific tau protein isoforms. Imaging studies suggest that there may be sensitive and specific means to differentiate PSP from other parkinsonian disorders, but identification of a diagnostic biomarker is still elusive.     

Nosocomial outbreak of CTX-M-15-producing E. coli in Norway

Seven E. coli isolates expressing resistance to 3rd generation cephalosporins were recovered from blood (n=2), kidney and lung tissue (n=1), and urinary tract (n=4) samples from seven patients hospitalised or recently discharged from the Divisions of Geriatrics and Pulmonary Medicine, Central Hospital of Rogaland, between July and September 2004. All isolates expressed a typical ESBL-cefotaximase profile (cefotaxime MIC>ceftazidime MIC) with clavulanic acid synergy. A bla(CTX-M-15) genotype was confirmed in six strains that were coresistant to gentamicin, nitrofurantoin, trimethoprim-sulfamethoxazole and ciprofloxacin. A bla(CTX-M-3) genotype was detected in the last strain. XbaI-PFGE patterns of the six bla(CTX-M-15) isolates revealed a clonal relationship. Bla(CTX-M-15) strains were also positive for the ISEcp1-like insertion sequences that have been shown to be involved in the mobilization of bla(CTX-M.) Further analyses revealed two bla(CTX-M-15)-positive E. coli urinary isolates clonally related to the outbreak strain from two different patients at the same divisions in January and February 2004. These patients were later re-hospitalised and one had E. coli with an ESBL-cefotaximase profile in sputum and nasopharyngeal specimen during the outbreak period. Clinical evaluation suggests that the CTX-M-producing E. coli strains contributed to death in three patients due to delayed efficient antimicrobial therapy. The outbreak emphasises the epidemic potential of multiple-antibiotic-resistant CTX-M-15-producing E. coli also in a country with low antibiotic usage and low prevalence of antimicrobial resistance.     

Thymic stromal lymphopoietin augments the cytolytic activity of the human natural killer cell line NK-92

Culturing the human natural killer cell line NK-92 for 24 h in the presence of thymic stromal lymphopoietin (TSLP) potentiated its cytotoxic capacity against the erythroleukemia cell line K562. Longer incubation times did not augment the NK activity any further. No synergistic effects with respect to either proliferation or cytotoxicity were observed when TSLP was mixed with suboptimal concentrations of IL-2. FACS analysis of the NK-92 cells indicated expression of TSLPR but not the other component of the TSLP receptor complex, namely IL-7Ralpha. Some of the surface molecules known to be involved in NK cell-mediated cytotoxicity were also monitored. None of the receptors analyzed altered their expression to any major extent upon culture in TSLP or IL-2. However, a limited number of NK-92 cells were observed that had a rather low CD94/NKG2A expression, which increased upon stimulation with TSLP or IL-2.     

Breed relationships facilitate fine-mapping studies: a 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds

The features of modern dog breeds that increase the ease of mapping common diseases, such as reduced heterogeneity and extensive linkage disequilibrium, may also increase the difficulty associated with fine mapping and identifying causative mutations. One way to address this problem is by combining data from multiple breeds segregating the same trait after initial linkage has been determined. The multibreed approach increases the number of potentially informative recombination events and reduces the size of the critical haplotype by taking advantage of shortened linkage disequilibrium distances found across breeds. In order to identify breeds that likely share a trait inherited from the same ancestral source, we have used cluster analysis to divide 132 breeds of dog into five primary breed groups. We then use the multibreed approach to fine-map Collie eye anomaly (cea), a complex disorder of ocular development that was initially mapped to a 3.9-cM region on canine chromosome 37. Combined genotypes from affected individuals from four breeds of a single breed group significantly narrowed the candidate gene region to a 103-kb interval spanning only four genes. Sequence analysis revealed that all affected dogs share a homozygous deletion of 7.8 kb in the NHEJ1 gene. This intronic deletion spans a highly conserved binding domain to which several developmentally important proteins bind. This work both establishes that the primary cea mutation arose as a single disease allele in a common ancestor of herding breeds as well as highlights the value of comparative population analysis for refining regions of linkage.     

Detection of a de novo interstitial 2q microdeletion by CGH microarray analysis in a patient with limb malformations, microcephaly and mental retardation

We describe the cytogenetic diagnosis using BAC- and oligonucleotide microarrays of a 16-year-old Laotian-American female, who first presented at 2 1/2 years of age with microcephaly, developmental retardation, and skeletal abnormalities of the upper limb including mild syndactyly of the second and third and the third and fourth fingers, short middle phalanges and clinodactyly of the fifth digit at the distal interphalangel joint on both hands, and symphalangism of the metacarpal-phalangeal joints of the second and fifth digits bilaterally. Her lower limbs displayed symphalangism of the metatarsal-phalangeal joint of the second, third, and fourth digits on both feet, with fusion of the middle and distal phalanges of the second and fifth digits and hallux valgus bilaterally. G-banded chromosomal study at age 4 was normal. However, comparative genomic hybridization at age 15 with the Spectral Genomics 1 Mb Hu BAC array platform indicated a microdeletion involving two BAC clones, RP11-451F14 --> RP11-12N7 at 2q31.1. The maximal deletion on initial analysis comprised the HOXD cluster, which is implicated in limb development. Fluorescence in situ hybridization (FISH) using the RP11-451F14 probe confirmed the deletion. Both parents were negative for the deletion. Additional FISH using BAC RP11-387A1, covering the HOXD cluster, limited the maximal deletion to approximately 2.518 Mb, and excluded involvement of the HOXD cluster. The Agilent 44K and 244K platforms demonstrated a deletion of approximately 2,011,000 bp, which did not include the HOXD cluster. The malformations in our patient may be caused by deletion of a regulatory element far upstream of the HOXD cluster.     

Immune responses to borrelial VlsE IR6 peptide variants

Laboratory confirmation of Lyme borreliosis (LB) relies mainly on the demonstration of anti-borrelial antibodies. In recent studies, a novel VlsE protein IR₆ peptide-based assay has been introduced. Our aim was to evaluate the IR₆ peptides from three Borrelia burgdorferi sensu lato genospecies in the serodiagnosis of European and North American patients. Five VlsE protein IR₆ peptide variants representing sequences from B. burgdorferi sensu stricto, B. garinii, and B. afzelii were used as antigens in both IgG and IgM enzyme-linked immunosorbent assays (ELISA). Serum antibodies of 187 patients at different stages of LB from Europe and the United States were evaluated for serodiagnosis. For comparison samples were tested with one of the commercial IR₆ ELISAs. Three B. afzelii IR₆ variant peptides revealed antibodies that were concordant with each other. B. burgdorferi sensu stricto peptide antibodies mostly paralleled B. afzelii peptide antibodies, and positive values were also obtained in the majority of European sera. For several sera, B. garinii IR₆ peptide antibodies were discordant to B. afzelii peptide antibodies. The commercial IR₆ peptide antibody assay (C6 ELISA) results correlated better with B. burgdorferi sensu stricto IR₆ than with B. garinii IR₆ peptide IgG results, especially in sera from patients with facial palsy. Thus, antibody specificity to IR₆ peptides may vary according to the infecting Borrelia species. In some manifestations of the disease, C6 ELISA may not cover all LB cases. Evidently, the methodological aspects in ELISA design for peptide antibody measurements are important as well as the amino acids sequence of the antigen.