Infection risk prevention following total knee arthroplasty.

INTRODUCTION: Implant infection is serious; prevention is mandatory, and requires assessment.The present study assessed the incidence of deep surgical-site infection (SSI) at 1 year following total knee arthroplasty (TKA) and adherence to skin preparation, antibiotic prophylaxis,screening and prevention in case of methicillin-resistant S. aureus (MRSA). HYPOTHESIS: Adherence to prevention measures reduces infection risk secondary to TKA. MATERIAL AND METHODS: A prospective study of the incidence of SSI following primary TKA was run from December 1st 2005 to December 31st 2006 in a continuous series of 364 operations in 359 patients, excluding cases of septic or aseptic revision. Each implant was followed up for 12 months. Adherence to practice was assessed by independent observers. Antibiotic prophylaxis was assessed; skin preparation was scored (out of 10); MRSA was systematically screened for, and preventive measures were assessed in positive cases. Median follow-up was 12 months.Patients with less than 11 months' FU were contacted by telephone. Median age was 72 years(range, 45-92 years). Eighty-seven percent of patients had ASA scores of 2; 14% were diabetic,and 42% obese. Mean surgery time was 70 min (range, 30-164 min). Among the implants, 81.5% were cemented. Eighty-six percent of operations had NNIS scores of 0. Infection risk linked to theater environment and teams was under control. RESULTS: Fourteen patients were lost to follow-up and excluded from analysis. The incidence of infection was 1.4% (n = 5/350) (95% CI [0.41-3.22]). Three of the infections were early (

HIV-1 drug-resistance patterns among patients on failing treatment in a large number of European countries.

BACKGROUND: Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy. METHODS: The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries. Genotypic resistance was interpreted using the ANRS algorithm. Phenotypic resistance was predicted using the Virco geno- to phenotype system. RESULTS: 80.7% of the sequences included at least one drug-resistance mutation. Mutations were found for NRTIs (73.5%), NNRTIs (48.5%), and protease inhibitors (35.8%). Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. Among NRTIs, resistance was most frequently predicted for lamivudine. About half of all sequences had reduced susceptibility for NNRTIs. Resistance to most boosted protease inhibitors was found in < 25%. No sequence had resistance to all currently available drugs. CONCLUSION: Levels of resistance among patients with therapy failure were high. The patterns of resistance reflect resistance to drugs available for a longer time. Fully suppressive regimens can be designed even for the most mutated HIV because boosted protease inhibitors have remained active against most circulating viruses and new drug classes have become available.

The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts.

BACKGROUND: The HIV-1 protease mutation I50 L causes atazanavir resistance but increases susceptibility to other PIs. Predicted phenotypic FC values were obtained from viral genotypes, using the virtual Phenotype-LM bioinformatics tool (powering vircoTYPE). OBJECTIVE: To evaluate I50 L's effect on susceptibility to 8 PIs, in a large genotype database. STUDY DESIGN: I50 L containing routine clinical isolate samples in Virco's genotype database were paired with samples having like patterns (or profiles) of IAS-USA-defined primary PI mutations, but lacking I50 L. Using vircoTYPE (version 4.1), the median predicted FC for each mutational profile was determined. I50 L-associated shifts in FC were evaluated using drug-specific CCOs. RESULTS: We selected 307 and 37098 samples with and without I50 L. These corresponded to 31 mutation patterns of > or =3 samples each. I50 L caused resistance to atazanavir in all 31 mutation contexts, but was associated with higher susceptibility for other PIs. The largest I50 L-associated shifts in median predicted FC were: 1.2 to 42.4 (atazanavir), 10.2 to 3.2 (amprenavir), 3.3 to 0.5 (darunavir), 13 to 0.5 (indinavir), 34.9 to 1.3 (lopinavir), 22.3 to 1.3 (nelfinavir), 5.2 to 0.3 (saquinavir) and 29.9 to 5.2 (tipranavir). CONCLUSIONS: The PI mutation I50 L causes clinically relevant resistance and increased susceptibility to atazanavir and other PIs respectively.

Prediction of HIV-1 drug susceptibility phenotype from the viral genotype using linear regression modeling.

Linear regression modeling on a database of HIV-1 genotypes and phenotypes was applied to predict the HIV-1 resistance phenotype from the viral genotype. In this approach, the phenotypic measurement is estimated as the weighted sum of the effects of individual mutations. Higher order interaction terms (mutation pairs) were included to account for synergistic and antagonistic effects between mutations. The most significant mutations and interactions identified by the linear regression models for 17 approved antiretroviral drugs are reported. Although linear regression modeling is a statistical data-driven technique focused on obtaining the best possible prediction, many of these mutations are also known resistance-associated mutations, indicating that the statistical models largely reflect well characterized biological phenomena. The performance of the models in predicting in vitro susceptibility phenotype and virologic response in treated patients is described. In addition to a high concordance with in vitro measured fold change, which was the primary aim of model design, the models per drug show good predictivity of therapy response for regimens including that drug, even in the absence of other clinically relevant factors such as background regimen.

Culture and immunological detection of Tropheryma whippelii from the duodenum of a patient with Whipple disease.

CONTEXT: Culture of Tropheryma whippelii has been established only once, in human fibroblast cell lines from a heart valve inoculum. Molecular-based diagnostic techniques, although highly sensitive, may be less specific. New diagnostic tools involving isolation of bacteria from contaminated intestinal biopsies and immunohistological detection need to be developed. OBJECTIVE: To describe a novel method for detection and culture of T whippelii strains. DESIGN, SETTING, AND SUBJECTS: Laboratory analysis of duodenal biopsy specimens from a patient with typical relapsing Whipple disease with intestinal involvement, performed Marseille, France, in March 2000. Biopsy specimens were decontaminated with antimicrobial agents and inoculated onto cell cultures. Mouse anti-T whippelii polyclonal antibodies were used to detect T whippelii in fixed specimens taken from the patient before and after relapse, compared with specimens from 10 controls. The genotype of the isolate was determined by amplification and sequencing of 2 DNA fragments (ITS and 23S rRNA). MAIN OUTCOME MEASURE: Isolation and genotyping of a new strain(s) of T whippelii from the case patient's biopsy specimens. RESULTS: A strain was grown from the case patient's intestinal specimen that has a genotype different from the first strain isolated. During 2 episodes of Whipple disease, T whippelii bacteria were detected by immunochemistry in the patient's duodenal biopsy specimens, but not in controls. CONCLUSIONS: A second strain of T whippelii has been isolated and a protocol for isolation from the intestine has been proven to be efficient. Immunodetection of T whippelii in intestinal biopsy specimens may provide a useful tool for the diagnosis and follow-up of patients with Whipple disease. Both techniques need further evaluation and confirmation.

Functional analysis of ZNF85 KRAB zinc finger protein, a member of the highly homologous ZNF91 family.

We previously identified the ZNF85 (HPF4) KRAB zinc finger gene, a member of the human ZNF91 family. Here, we show that the ZNF85 gene is highly expressed in normal adult testis, in seminomas, and in the NT2/D1 teratocarcinoma cell line. Immunocytochemical localization of a panel of beta-Gal/ZNF85 fusion proteins revealed that ZNF85 contains at least one nuclear localization signal located in the spacer region connecting the KRAB domain with the zinc finger repeats. Bacterially expressed ZNF85 zinc finger domain bound strongly and exclusively to DNA in vitro in a zinc-dependent manner. The KRAB(A) domain of the ZNF85 protein and of several other members of the ZNF91 family exhibited repressing activity when tested in Gal4 fusion protein assays. The repression was significantly enhanced by the addition of the KRAB (B) domain, whereas further addition of other conserved regions had no effect. The ZNF85 KRAB(A) and (B) domains in vitro bound several nuclear proteins that might constitute critical cofactors for repression.

Severe congenital hypopituitarism with low prolactin levels and age-dependent anterior pituitary hypoplasia: a clue to a PIT-1 mutation.

A 20-month-old boy presented with severe congenital growth hormone, thyrotropin, and prolactin deficiencies resulting from a de novo mutation of the PIT-1 gene. This form of congenital hypopituitarism should be suspected if pituitary anatomy is normal, especially if prolactin levels are low and, in boys, if the external genitalia are normal. Pituitary atrophy appears to be an age-dependent phenomenon in this condition.

Enhanced expression in seminoma of human zinc finger genes located on chromosome 19.

Six Krüppel-type zinc finger (ZF) genes were cloned from a seminoma cDNA library. One, ZFS-1, showed high sequence homology to the ZNF91 KRAB (Krüppel-associated box) ZF gene family and also the same chromosomal assignment. Interestingly, Northern blot analyses using ZFS-1 and ZNF91 revealed that multiple ZF genes on chromosome 19 were predominantly expressed in seminomas. In addition, the testis and the seminoma showed specific expression of 2.3 kb transcript. Our results suggest that ZF genes on chromosome 19 may be implicated in the development and/or growth of seminomas.

[Guillain-Barré syndrome complicating cytomegalovirus infection in an immunocompetent adult]. / Syndrome de Guillain-Barré compliquant une infection à cytomégalovirus chez un adulte immunocompétent.

Guillain-Barré syndrome is a rare complication of cytomegalovirus infection in the healthy adult. We report a new case with good spontaneous outcome. Cytomegalovirus has been recognized in about 15% of Guillain-Barré syndromes. Clinical and biological presentation, and outcome are common and prognosis is often good. Etiopathogenic mechanism is unclear.

Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells.

KRAB zinc-finger proteins (KRAB-ZFPs) constitute a large subfamily of ZFPs of the Krüppel C2H2 type. KRAB (Krüppel-associated box) is an evolutionarily conserved protein domain found N-terminally with respect to the finger repeats. We report here the characterization of a particular subgroup of highly related human KRAB-ZFPs. ZNF91 is one representative of this subgroup and contains 35 contiguous finger repeats at its C-terminus. Three mRNA isoforms with sequence identity to ZNF91 were isolated by the polymerase chain reaction. These encode proteins with a KRAB domain present, partially deleted or absent. Five genomic fragments were characterized, each encoding part of a gene: the ZNF91 gene or one of four distinct, related KRAB-ZFP genes. All exhibit a common exon/intron organization with the variant zinc finger repeats organized in a single exon and the KRAB domain encoded by two separate exons. This positioning of introns supports the hypothesis that the mRNA isoforms encoding polypeptides with variability in the KRAB domain could arise by alternative splicing. By in situ chromosomal mapping studies and by analysis of fragments from a human genomic yeast artificial chromosome library containing KRAB-ZFP genes, we show that these genes occur in clusters; in particular, a gene complex containing over 40 genes has been identified in chromosomal region 19p12-p13.1. These ZNF91-related genes probably arose late during evolution since no homologous genes are detected in the mouse and rat genomes. Although the transcription of members of this KRAB-ZFP gene subgroup is detectable in all human tissues, their expression is significantly higher in human T lymphoid cells.

Efficacy, safety and tolerance of parenteral piperacillin/tazobactam in the treatment of patients with lower respiratory tract infections.

An open, non-comparative multicentre study was conducted at 36 sites in six countries to test the efficacy and safety of piperacillin/tazobactam in the therapy of lower respiratory tract infections. Piperacillin 4 g and tazobactam 500 mg were administered intravenously every 8 h for a minimum of five days. Two hundred and thirty patients were enrolled: 133 were evaluable for clinical efficacy and 106 for bacteriological efficacy. The clinical response was favourable in 96% of evaluable patients and the bacterial eradication rate was 93%. Nine patients (4%) had severe adverse events related to piperacillin/tazobactam and requiring discontinuation of therapy. In this study piperacillin/tazobactam was an effective and safe drug in the treatment of hospitalized patients with lower respiratory tract infection caused by sensitive organisms.

The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins.

We have previously shown that the human genome includes hundreds of genes coding for putative factors related to the Krüppel zinc-finger protein, which regulates Drosophila segmentation. We report herein that about one-third of these genes code for proteins that share a very conserved region of about 75 amino acids in their N-terminal nonfinger portion. Homologous regions are found in a number of previously described finger proteins, including mouse Zfp-1 and Xenopus Xfin. We named this region the Krüppel-associated box (KRAB). This domain has the potential to form two amphipathic alpha-helices. Southern blot analysis of "zoo" blots suggests that the Krüppel-associated box is highly conserved during evolution. Northern blot analysis shows that these genes are expressed in most adult tissues and are down-regulated during in vitro terminal differentiation of human myeloid cells.

[A case of Whipple's disease with ankylosing spondylarthritis treated with trimethoprim-sulfamethoxazole]. / Un cas de maladie de Whipple avec spondylarthrite ankylosante traité par triméthoprime-sulfaméthoxazole.

We report the case of a patient, suffering from Whipple's disease and HLA B27 positive ankylosing spondylitis with syndesmophytes and erosive discopathy. Since spinal radiographic aspects of spondylitis due to Whipple's disease are unusual, we are debating on their relation. We, then, took an interest in the treatment given to this patient: trimethoprim-sulfamethoxazole which would now appear to be the best antibiotic for Whipple's disease.