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Biomedical subjects

F Denis

Publications and source records attributed to F Denis.

At least 19 recordsLinked to original sources

Postoperative deep wound infection in adults after posterior lumbosacral spine fusion with instrumentation: incidence and management.

The authors reviewed 817 instrumented lumbosacral fusions in adults and found an incidence of 3.2% deep wound infections. The primary focus of this study was the management of these infections, with particular attention to whether the implants needed to be removed. A consulting infectious disease specialist indicated that an acute infection of a low back fusion wound could not be healed without removal of the metallic implants. This opinion was in contrast to the authors' daily experience and prompted this study. The authors identified and reviewed 817 cases of instrumented posterior lumbosacral arthrodeses in adults. A detailed analysis of any case with a deep wound infection was performed and yielded and infection rate of 3.2% (26 patients). Of these, 24 achieved a clean, closed wound without removal of instrumentation through a protocol of aggressive debridement and secondary closure. Instrumentation removal is not necessary to obtain a clean, closed wound using an aggressive approach with early diagnosis, vigorous debridement in the operative room under general anesthesia, delayed primary or secondary closure, and appropriate antibiotic coverage.

Acute Disease

Management of symptomatic lumbar pseudarthrosis with anteroposterior fusion. A functional and radiographic outcome study.

STUDY DESIGN: An independent retrospective review of 37 patients undergoing 39 anteroposterior lumbar fusions for lumbar pseudarthrosis repair between 1984 and 1990. OBJECTIVES: To evaluate radiographically and functionally the results of the combined anteroposterior fusion for the management of symptomatic lumbar pseudarthrosis, and to assess risk factors for functional failure after the procedure. SUMMARY OF BACKGROUND DATA: Most reported techniques of pseudarthrosis repair involve posterior fusion with no instrumentation, posterior fusion with instrumentation, or anterior fusion alone. The results of lumbar pseudarthrosis repair are poor. Fusion rates range from 30% to 70%, with only a 30% to 50% rate of functional success. METHODS: Thirty-nine procedures were assessed in 37 patients. The outcomes were assessed radiographically (solid fusion vs. pseudarthrosis) and functionally (success vs. failure). Radiographs were assessed at follow-up examination for consolidation of fusion anteriorly and posteriorly. Functional outcome was graded by using multiple instruments, including data from chart review and the follow-up outcome questionnaire. A functional failure score that took into account 10 items was developed. RESULTS: In this patient population (37 patients, 59% with a smoking history, 71% with compensation or legal claims), there was a 10% pseudarthrosis rate. Pseudarthrosis was defined when one or more levels were involved and when it occurred anteriorly and posteriorly. In 12 patients (35%), the outcome was rated as functional failure. The presence of one or more abnormal neurologic findings and significant narcotic use before surgery significantly increased the chance of a patient's outcome being functional failure. Workmen's Compensation or legal status before surgery also increased the chance of functional failure, though this correlation was not statistically significant. CONCLUSIONS: A combined anterior and posterior approach for the management of symptomatic lumbar pseudarthrosis is a viable alternative to posterior fusion alone. In fact, this procedure affords a higher fusion rate based on radiographic assessment. Functional failure rates may be decreased by using caution for those patients using narcotics regularly before surgery or in those with unexplained preoperative neurologic abnormal findings.

Adult

Prevalence of vancomycin-resistant enterococci in fecal samples from hospitalized patients and nonhospitalized controls in a cattle-rearing area of France.

Vancomycin-resistant enterococci (VRE) have emerged as nosocomial pathogens over the last decade, but little is known about their epidemiology. We report on the prevalence of VRE fecal colonization on the basis of a prospective study among patients hospitalized in a hematology intensive care unit and among nonhospitalized subjects living in the local community. A total of 243 rectal swabs from hematology patients and 169 stool samples from the control group were inoculated onto bile-esculin agar plates with and without 6 mg of vancomycin per liter and into an enrichment bile-esculin broth supplemented with 4 mg of vancomycin per liter. A total of 37% of the hospitalized patients and 11.8% of the subjects from the community were found to be VRE carriers. A total of 65 VRE strains were isolated: 12 (18.5%) E. faecium, 46 (70.7%) E. gallinarum, and 7 (10.8%) E. casseliflavus strains. No E. faecalis strains were detected. All the E. faecium strains were of the vanA genotype. Molecular typing by pulsed-field gel electrophoresis revealed a different pattern for each vanA VRE strain that originated from an individual subject. To our knowledge, this is the first study to be carried out in a cattle-rearing region of France. It reports a higher VRE prevalence than that reported in previous European or U.S. studies. A partial explanation is the use of an enrichment broth step which enabled detection of strains which would otherwise have been missed, but the fact that subjects and patients were recruited from a predominantly agricultural area where vancomycin-related antibiotics have recently been used in animal husbandry could also contribute to the high levels of VRE in patients and subjects alike.

Adolescent

Alternative proteolytic processing of mouse mammary tumor virus superantigens.

Mouse mammary tumor viruses express a superantigen essential for their life cycle. It has been proposed that viral superantigens (vSags) require processing by prohormone convertases (PCs) for activity. We now observe, using a panel of mutant forms of potential PC cleavage sites and in vitro cleavage assays, that only the CS1 (position 68 to 71) and CS2 (position 169 to 172) sites are utilized by furin and PC5. Other members of the convertase family that are expressed in lymphocytes are not endowed with this activity. Furthermore, mutant forms of two different viral superantigens, vSag7 and vSag9, which completely abrogated in vitro processing by convertases, were efficient in functional presentation to responsive T-cell hybridomas. This effect was observed in both endogenous presentation and paracrine transfer of the vSag. Processing by convertases thus appears not to be essential for vSag function. Finally, we have identified the purified endosomal protease cathepsin L as another protease that is able to cleave convertase mutant vSag in vitro, yielding fragments similar to those detected in vivo, thus suggesting that proteases other than convertases are involved in the activation of vSags.

Alternative Splicing

[Human herpesviruses 6 and 7 (HHV-6 and HHV-7)].

Human herpesviruses 6 (HHV-6) and 7 (HHV-7) are world wide T lymphotropic viruses recently discovered. Their transmission is essentially by salivary route. Primary infections which occurred early in infancy, respectively during the first year of life for HHV-6 and in the second or third year for HHV-7, are followed by latency for life. HHV-7 is not actually associated with a disease. HHV-6 primary infection is often asymptomatic, if not it can induce exanthem subitum. HHV-6 reactivation can be symptomatic in immunodeficient subjects. The role of HHV-6 in the arising of lymphoproliferative or auto-immune diseases, discussed for a long time, is still to elucidate. HHV-6 infection is diagnosed by serodiagnosis in case of primary infection, but in the great number of cases, it would be realized by polymerases chain reaction.

Child, Preschool

The connecting peptide domain of pT alpha dictates weak association of the pre-T cell receptor with the TCR zeta subunit.

Signals delivered through the pre-TCR, a heterodimer of pT alpha and TCR beta chains, are crucial for the maturation and proliferation of immature alphabeta lineage thymocytes from the CD4- CD8- to the CD4+ CD8+ stage. To gain insight into the structural and functional properties of the pre-TCR, chimeric TCR alpha chains were generated by replacing domains of the alpha chain cytoplasmic, transmembrane and constant regions with homologous domains from the pT alpha chain. All chimeric TCR could be expressed stably at the cell surface and induce Ca2+ mobilization as well as phosphorylation of several protein substrates on tyrosine residues. However, chimeras wherein the connecting peptide of TCR alpha chain was substituted by the one from pT alpha, were weakly associated with the TCR zeta chain, showing that functional but not physical interactions were preserved in such chimeras. In contrast, introduction of the connecting peptide of TCR alpha in the pT alpha chain was insufficient to confer stable association with the TCR zeta chain. These results demonstrate that the inability of the pre-TCR to interact strongly with TCR zeta is attributable to amino acid residues present throughout the region comprised between the intrachain Cys and the transmembrane domain. It remains to be determined whether the weak physical interaction between the pre-TCR alphand the zeta2 homodimer prevents the activation of specific TCR zeta-dependent signaling pathways, and thus confers unique signaling properties upon the pre-TCR. In addition, this structural difference between the pT alpha/beta and alphabeta TCR might constitute a means to regulate the expression of these receptors at the surface of thymocytes, at different stages of their maturation.

Amino Acid Sequence

Evaluation of BC-3 and BCP-1 cell lines in immunofluorescence assay to detect HHV-8 antibodies in Kaposi's sarcoma, multiple myeloma and other groups.

BACKGROUND: We describe a comparative study of an immunofluorescence assay using inducible BC-3 and BCP-1 cell lines as sources of HHV-8 antigens. STUDY DESIGN: Detection of both antibodies to proteins expressed in lytic cycle and during latency in sera from HIV-infected patients with KS, HIV-positive patients without KS, normal blood donors, HIV-negative pregnant women and HIV-negative patients with multiple myeloma. Where possible, detection of antibody was associated with nested PCR detection of HHV-8 in peripheral mononuclear cell (PBMC) samples collected from AIDS-KS patients. RESULTS: Immunofluorescence was more intense with the BC-3 cell line than with BCP-1, thus facilitating examination under the microscope. HHV-8 antibodies were detected among 82.75% of AIDS-KS patients, in 27.3% of HIV-infected homosexual men, 2% of blood donors and in 2% of pregnant women. No HHV-8 antibodies were detected in serum samples from HIV-negative patients presenting multiple myeloma. HHV-8 DNA sequences were detected and confirmed by southern blot hybridization in five out of 17 (29.4%) PBMC samples from AIDS-KS patients. Titre of antibodies to proteins expressed in lytic cycle was much higher than the titre of antibodies to proteins expressed during latency. CONCLUSIONS: Both immunofluorescence assays were found useful and HHV-8 seroprevalence rates reported in previous studies were confirmed. In addition, results obtained using these assays tend to provide evidence for a lack of epidemiological association between HHV-8 infection and development of multiple myeloma.

Adult

Management of an unstable lumbar fracture with a laminar split.

This is a case report describing the injury sustained by a 36-year-old man injured in a motorcycle crash who sustained a fracture dislocation of L2 upon L3, associated with a split in the lamina of L3. His neurologic lesion was T12 ASIA B: with a motor score of 52 but with preservation of sensory function (sensory score 96) in most parts of his lower extremities. He also suffered a lower extremity fracture. Imaging of the spine is presented showing a multiplanar fracture associated with translation and with a defect in the lamina that may be seen in certain AO type B or type C fractures, that may entrap the lumbar spinal nerve roots. Discussants of this case comment on the classification and clinical significance of this fracture pattern. and present their operative approaches, both for management of this particular fracture pattern and for any associated dural tear. The issues of steroid use and the place of rehabilitation are also discussed.

Accidents, Traffic

Characterization of the chromosomal aac(6')-Iz gene of Stenotrophomonas maltophilia.

The aac(6')-Iz gene of Stenotrophomonas maltophilia BM2690 encoding an aminoglycoside 6'-N-acetyltransferase was characterized. The gene was identified as a coding sequence of 462 bp corresponding to a protein with a calculated mass of 16,506 Da, a value in good agreement with that of ca. 16,000 found by in vitro coupled transcription-translation. Analysis of the deduced amino acid sequence indicated that the protein was a member of the major subfamily of aminoglycoside 6'-N-acetyltransferases. The enzyme conferred resistance to amikacin but not to gentamicin, indicating that it was an AAC(6') of type I. The open reading frame upstream from the aac(6')-Iz gene was homologous to the fprA gene of Myxococcus xanthus (61% identity), which encodes a putative pyridoxine (pyridoxamine) 5'-phosphate oxidase. Pulsed-field gel electrophoresis of total DNA from BM2690 and S. maltophilia ATTC 13637 digested with XbaI, DraI, and SpeI followed by hybridization with rRNA and aac(6')-Iz-specific probes indicated that the gene was located in the chromosome. The aac(6')-Iz gene was detected by DNA-DNA hybridization in all 80 strains of S. maltophilia tested. The MICs of gentamicin against these strains of S. maltophilia were lower than those of amikacin, netilmicin, and tobramycin, indicating that production of AAC(6')-Iz contributes to aminoglycoside resistance in S. maltophilia.

Acetyltransferases

Complications associated with pedicle screws.

BACKGROUND: The safety and the effectiveness of pedicle-screw instrumentation in the spine have been questioned despite its use worldwide to enhance stabilization of the spine. This review was performed to answer questions about the technique of insertion and the nature and etiology of complications directly attributable to the screws. METHODS: We performed a retrospective review of all of the pedicle-screw procedures that were done by us from January 1, 1984, to December 31, 1993. We inserted 4790 screws during 915 operative procedures on 875 patients; 668 (76.3 percent) of the patients had a lumbosacral arthrodesis. The mean duration of follow-up was three years (range, two to five years). The accuracy of screw placement was assessed on intraoperative, immediate postoperative, and follow-up radiographs with use of a technique that was developed by one of us (F. D.); this technique has yet to be validated to determine the prevalence of various types of error. RESULTS: Of the 4790 screws, 4548 (94.9 percent) had been inserted within the pedicle and the vertebral body. One hundred and thirty-four (2.8 percent) of the screws had perforated the anterior cortex, and this was the most common type of perforation. One hundred and fifteen (2.4 percent) of the screws were associated with complications that could be ascribed to the use of pedicle screws. The most common problem was late-onset discomfort or pain related to a pseudarthrosis or perhaps to the screws; this problem was associated with 1102 (23.0 percent) of the screws, used in 222 (24.3 percent) of the procedures. The symptoms necessitated removal of the instrumentation with or without repair of the pseudarthrosis. A pseudarthrosis was found during forty-six (20.7 percent) of the 222 procedures. Irritation of a nerve root occurred after nine procedures (1.0 percent) and was caused by eleven screws (0.2 percent); it was more commonly caused by medially placed screws. Three patients had residual neurological weakness despite removal of the screws. Twenty-five screws (0.5 percent), used in twenty procedures (2.2 percent), broke. The screws that broke were of an early design. A pseudarthrosis was found in thirteen of twenty patients who had broken screws. Sixteen of the twenty patients had an exploration; three of them were found to have a solid fusion, and thirteen were found to have a pseudarthrosis. The remaining four patients had evidence of a solid fusion on radiographs and had no pain. CONCLUSIONS: There are few problems associated with the insertion of screws, provided that the surgeon is experienced and adheres to the principles and details of the operative technique. Our review revealed a low rate of postoperative complications related to pedicle screws. The problem of late-onset pain may be related to the implants or to the stiffness of the construct; however, it is difficult to accurately identify its exact etiology.

Adolescent

'Mass-murder' of ORFs from three regions of chromosome XI from Saccharomyces cerevisiae.

The complete sequence of the yeast Saccharomyces cerevisiae reveals the presence of many new genes, many of which are without homologs in databases. Characterisation of these genes by novel methods includes systematic deletion followed by phenotypic analysis of mutant strains. We have developed a hierarchical strategy for such a functional analysis of genes, in which the primary phenotypic screening is performed on groups of contiguous genes which are then reinvestigated down to the single gene level. This strategy is applied to the whole chromosome XI as part of EUROFAN (the EUROpean Functional ANalysis) program, and we present here our results on a group of 22 genes from this chromosome. This sample is representative of the results that are emerging for the whole chromosome. Out of the 22 genes deleted, three were shown to be essential, and another three genes confer a mutant growth phenotype to cells when deleted. All phenotypes have been complemented. These figures are in accordance with the previously published fraction of lethal and growth-defective deletions of single genes. We have found no synthetic phenotypes resulting from a combination of deleted genes and have always been able to attribute a mutant phenotype to a single gene.

Chromosomes

Coronal and sagittal balance in surgically treated adolescent idiopathic scoliosis with the King II curve pattern. A review of 67 consecutive cases having selective thoracic arthrodesis.

STUDY DESIGN: A retrospective study by an independent observer of a consecutive series of 67 cases of adolescent idiopathic scoliosis presenting with a King II curve pattern. OBJECTIVES: To demonstrate the validity of a selective thoracic fusion as a treatment of King II curves with special attention to immediate postoperative and long-term trunk balance in the coronal and sagittal planes. SUMMARY OF THE BACKGROUND DATA: The literature has been fairly controversial in terms of the recommended treatment of King II curve patterns in adolescent idiopathic scoliosis. The main confusion appears to be whether the thoracic curve alone or both curves should be instrumented and fused. METHODS: Sixty-seven patients were identified as having had a selective posterior thoracic spine fusion with instrumentation between 1961 and 1994. None of these cases had a fusion of the lumbar spine. Preoperative radiographs were analyzed for determination of the appropriate fusion level using the criteria of the stable and neutral vertebra. Follow-up radiographs were evaluated for balance in the coronal and sagittal planes using the central sacral line on posteroanterior radiograph and the C7 sacral promontory line on lateral film. RESULTS: At 2-year or greater follow-up, the unfused lumbar curve remained equal to or less than the corrected thoracic curve in 63 patients (94%). No patient required extension of fusion. Frontal plane balance analysis showed that 47 of the 67 patients had the T1 plumb line within 2 cm of the midline for an average decompensation of 8.7 mm. In no patient was the loss of balance greater than 3.8 cm. Sagittal plane balance analysis showed that only one patient had inferior junctional kyphosis greater than 10 degrees. This did not require extension of fusion. There were no cases of superior junctional kyphosis. CONCLUSIONS: The concept of selective thoracic fusion in the King II curve pattern appears to be valid. These findings suggest that arthrodesis of the lumbar spine can be avoided when this pattern is properly diagnosed and appropriately treated. Proper identification of the stable and neutral vertebra and of the appropriate level of fusion are important to achieve good postoperative balance. Successful preservation of lumbar motion segments is important to long-term satisfactory outcome in adolescent idiopathic scoliosis.

Adolescent

Highly biased CDR3 usage in restricted sets of beta chain variable regions during viral superantigen 9 response.

Superantigens encoded by the mouse mammary tumor virus can stimulate a large proportion of T cells through interaction with germline-encoded regions of the T cell receptor beta chain like the hypervariable region 4 (HV4) loop. However, several lines of evidence suggest that somatically generated determinants in the CDR3 region might influence superantigen responses. We stimulated T cells from donors differing at the BV6S7 allele with vSAG9 to assess the nature and structure of the T cell receptor in amplified T cells and to evaluate the contribution of non-HV4 elements in vSAG recognition. This report demonstrates that vSAG9 stimulation caused the expansion of TCR BV6-expressing T cells, although to varying degrees depending on the BV6 subfamily. The BV6S7 subfamily was preferentially expanded in all donors, but in donors homozygous for the BV6S7*2 allele, a significant number of BV6S5 T cells were amplified and showed a highly biased beta chain junctional region (BJ) and CDR3 usage. As CDR3 regions are involved in major histocompatibility complex (MHC)-peptide interaction, such a selection is highly suggestive of an intimate MHC-TCR interaction and would imply that the topology of the MHC-vSAG-TCR complex is similar to the one occurring during conventional antigen recognition.

Amino Acid Sequence

The role of caspases in T cell development and the control of immune responses.

Apoptosis is responsible for the removal of potentially autoreactive or useless T cells during thymic selection and activated T cells in the periphery. Specific families of receptors, kinases, transcription factors, and cysteine proteases, termed caspases, are involved in the apoptotic cascade leading to proteolysis of specific substrates and to morphological changes associated with programmed cell death. Although common members of the apoptotic cascade are shared between different cell types, it appears that cell-specific factors can influence the response to a given apoptotic stimuli. Characterization and understanding of the basic mechanisms involved in the different pathways protecting or leading to cell death may provide novel ways to control inappropriate apoptosis involved in several diseases.

Animals

Intrafamilial clustering and 4-year follow-up of asymptomatic human T-cell leukaemia virus type I (HTLV-I) infection in Benin (West Africa).

BACKGROUND: Few data exist concerning familial human T-cell leukaemia virus type I (HTLV-I) carrier states and transmission in African countries. Two previous surveys performed in Benin in 1989 and 1990 using a three-level cluster sampling method allowed us to identify HTLV-I positive subjects. The evolution of HTLV-I within the families of these subjects is described over a 4-year period, 1991-1995. METHODS: Since 1991, 37 HTLV-I seropositive subjects, six subjects with indeterminate Western-Blot pattern, and their relatives have been followed up once a year clinically and biologically. RESULTS: Twenty-three mothers in the study group gave birth to 27 children between 1991 and 1995. Among the 13 infants born to the 12 seropositive mothers, two seroconverted before their second birthday. One adult woman whose husband was seropositive developed seropositivity 4 years after marriage. In March 1992, a family case-control study (proband study) was conducted. A seroprevalence of 27.5% was found among 138 relatives of 32 infected subjects and 1.4% among 142 relatives of 32 control subjects. CONCLUSIONS: There is clearly an intrafamilial clustering of HTLV-I in Benin. The annual incidence density of HTLV-I in this cohort is estimated at 6 per thousand.

Adolescent