Excellent medium-term survival of an all-inside tensionable knotted suture device justifies repair of most meniscal tears encountered during reconstructive knee ligament surgery.

PURPOSE: All-inside meniscal repair devices have evolved to allow surgeons to undertake complex repairs in a timely and efficient manner. This is advantageous in active patients, where meniscus preservation is critical in preserving joint function and stability. The aim of the study was to evaluate the failure rate of all-inside meniscal repair performed in patients undergoing reconstructive ligament surgery using a particular meniscal repair device. METHODS: Patients were identified using a single-site prospectively maintained patient registry. Primary outcome was failure, defined as return to surgery with documented failure of repair. Complication rates and functional scores were also recorded. Patients in whom meniscal repair failure was identified were further assessed, to identify any common features. RESULTS: Over an 8-year period, 323 patients underwent meniscal repair at the time of ligament reconstruction, compared to 244 meniscectomies. Of these, 286 patients underwent repair using an all-inside suture device. One-hundred and twenty-seven repairs were to the medial meniscus only, 124 were lateral, and in 35 patients both menisci were repaired. Follow-up was to a median of 51.5 months. There were 31 (9.7%) failures reported at a median of 22 months post-operatively (IQR 13.5-41.5). Medial repair failures were seen more frequently than lateral (13.6% versus 5.6% OR 2.62 95% CI 1.17-5.88 p = 0.022). Failure of ACL reconstruction was associated with meniscal repair failure (OR 5.83 95% CI 1.55-21.95 p = 0.0039). Multi-ligament reconstruction was undertaken in 70/286 patients receiving meniscal repair and was not associated with failure (OR 1.3 95% CI 0.57-2.98 p = 0.51). Mode number of all-inside sutures used was 3 in both medial and lateral repairs (Range 1-9 lateral; 1-7 medial). CONCLUSIONS: All-inside repair is a safe and versatile technique which can be used in the majority of meniscal tears encountered during ligament reconstruction with excellent mid-term success. Failure is seen more commonly in medial sided repairs and with failure of ACL reconstruction. LEVEL OF EVIDENCE: IV.

Functions of the Magnaporthe oryzae Flb3p and Flb4p transcription factors in the regulation of conidiation.

The Magnaporthe oryzae genes FLB3 and FLB4, orthologues of the Aspergillus nidulans regulators of conidiation FlbC and FlbD, were inactivated. These genes encode C2H2 zinc finger and Myb-like transcription factors, respectively, in A. nidulans. Analysis of the resultant mutants demonstrated that FLB4 is essential for spore formation and that strains lacking this gene are fluffy in their colony morphology due to an inability to complete conidiophore formation. Meanwhile, FLB3 is required for normal levels of aerial mycelium formation. We identified genes dependent on both transcription factors using microarray analysis. This analysis revealed that the transcription of several genes encoding proteins implicated in sporulation in Magnaporthe oryzae and other filamentous fungi are affected by FLB3 or FLB4 inactivation. Furthermore, the microarray analysis indicates that Flb3p may effectively reprogramme the cell metabolically by repressing transcription of genes encoding biosynthetic enzymes and inducing transcription of genes encoding catabolic enzymes. Additionally, qRT-PCR was employed and showed that FLB3 and FLB4 transcripts are enriched in synchronously sporulating cultures, as were the transcripts of other genes that are necessary for normal conidiation, consistent with a role for their gene products in this process.

Biotinylation and characterization of Cryptococcus neoformans cell surface proteins.

AIMS: To develop a novel procedure for isolating and characterizing cryptococcal cell-surface proteins using biotinylation, fluorescein isothiocyanate (FITC)-streptavidin, flow cytometry and associated ligand-receptor analysis, confocal microscopy and electrophoretic separation. METHODS AND RESULTS: Cell proteins of both acapsulate and encapsulated Cryptococcus neoformans cells were labelled using sulfo-NHS-biotin which, in turn, was complexed with FITC-streptavidin. Resulting cell population fluorescence supported visualization of cell-surface protein distribution by confocal microscopy, as well as evaluation of protein exposure by flow cytometry and the calculation of the ligand-binding determinants EC(50), F(max) and H(n). Biotinylation of cell-surface proteins also supported their isolation by affinity chromatography and characterization by SDS/PAGE. Ligand-binding determinants, such as EC(50) values, indicated that acapsulate and stationary phase cells have greatest affinity for biotin. F(max) values demonstrated greatest protein exposure among stationary phase cells; in turn, encapsulated cells expose more protein than acapsulate counterparts. H(n) values of below unity potentially confirm the complex multi-receptor nature of biotin binding to cryptococcal cell surfaces under investigation. Fluorescence visualization showed marked but localized fluorescence indicative of protein exposure around sites of cell division. In turn, biotinylation of cell-surface proteins and their release under reducing conditions demonstrated at least two noncovalently linked proteinaceous entities, of 43 and 57 kDa, exposed on acapsulate cryptococcal cell walls. CONCLUSIONS: A novel method for identifying, in situ, cell-surface proteins exposed by C. neoformans was established. This novel technique was successfully implemented using both acapsulate and encapsulated C. neoformans cells, both were found to have dynamic and markedly localized protein distribution around sites of cell division and associated cell wall trauma. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel procedure, employing a versatile combination of flow cytometry, ligand-receptor analysis, confocal microscopy and biotinylation, supported the characterization and isolation of cryptococcal cell-surface proteins.

The results of immediate re-repair of zone 1 and 2 primary flexor tendon repairs which rupture.

This study reports the outcome of immediate re-repair of primary flexor tendon repairs in zones 1 and 2 of the fingers which had ruptured. Between June 1989 and May 2003, a total of 62 fingers in 61 patients presented with ruptured flexor tendon repairs within 48 hours from rupture. Immediate re-repair and rehabilitation was carried out in 44 fingers (71%) in 43 (70%) patients. Thirty-six patients completed the 8-week therapy programme after re-repair in 37 fingers. Nine (24%) had excellent, 10 (27%) good, 5 (14%) fair and 13 (35%) had poor results when assessed by the original Strickland method. Five fingers in five patients ruptured the re-repair. Poor results and second ruptures were particularly common after re-repair of ruptured tendon repairs in the little finger. In the light of these findings, a policy for dealing with ruptured primary flexor tendon repairs in the fingers is suggested.

Immediate repair and early mobilization of the extensor pollicis longus tendon in zones 1 to 4.

We present the results of repair and early mobilization of 100 extensor pollicis longus (EPL) tendon injuries in zones 1 to 4 in 100 patients using a dynamic outrigger splint which controlled metacarpophalangeal joint movements but allowed free movement of the interphalangeal joint. Eighty-two were complete divisions of the tendon and 18 were 80% to 99% tendon divisions. Analysis of measurements obtained routinely at 8 weeks showed 81% excellent and good results using the TAM system. There were 90% excellent and good results in the 72 patients, who were followed-up and received therapy for 12 weeks. Except on the rare occasion when the repair rupture, loss of thumb extension was not a common functional problem, but scar tethering of the repaired tendon could result in loss of thumb flexion. While loss of metacarpophalangeal joint flexion appeared to have little functional importance, loss of interphalangeal joint flexion and slowing of the movements of this joint could cause functional problems. When interphalangeal joint hyperextension is present before the injury, it is frequently lost but this generally goes unnoticed by the patients. The problems of analysing the EPL injury using the methods of assessment available are discussed.

A comparison of dynamic extension splinting and controlled active mobilization of complete divisions of extensor tendons in zones 5 and 6.

We present a prospective randomized trial of two groups of 50 patients each having complete zone 5 and 6 extensor tendon injuries. These were rehabilitated by the use of either a dynamic outrigger splint or a palmar blocking splint. The results were analysed using the Miller and TAM assessments. Good and excellent results were achieved in 95 and 98% of cases following dynamic outrigger mobilization and 93 and 95% of cases using palmar blocking splint mobilization, using the Miller and TAM assessments respectively. There was no statistical difference in the results obtained between the two groups. Therefore, we prefer the latter technique which is simple, cheap, more convenient and requires less therapy time.

The aetiology of acute rupture of flexor tendon repairs in zones 1 and 2 of the fingers during early mobilization.

Five hundred and eight patients with 840 acute complete flexor tendon injuries in 605 fingers in zones 1 and 2 underwent surgery and postoperative mobilization in a controlled or early active motion (active flexion-active extension) regimen over a period of 7.5 years. Sixty-eight patients with 79 finger flexor divisions who did not complete the rehabilitation programme were excluded. Of the 440 patients with 728 complete tendon divisions in 526 fingers included in the study, 23 patients ruptured 28 tendon repair(s) in 23 fingers, an overall rupture rate of 4%. One hundred and twenty-nine fingers with zone 1 injuries had a rupture rate of 5%. Three hundred and ninety-seven fingers with zone 2 injuries had a rupture rate of 4%. This study analyses the 23 patients with flexor tendon rupture(s) to identify causative factors. In approximately half of these patients, tendon rupture followed acts of stupidity. The implications of this are discussed. There was no significant relationship between tendon rupture and the age or sex of the patients, smoking or delay between injury and tendon repair and there was no particular prevalence of zone 2C level injuries among the fingers in which tendon rupture occurred.

The rôle of thymidine phosphorylase/PD-ECGF in cancer chemotherapy: a chemical perspective.

The angiogenic growth factor thymidine phosphorylase/PD-ECGF has been identified as a potential target in the development of anti-cancer drugs. This review firstly discusses the biological rôle of TP/PD-ECGF and its importance in the activation of 5-fluorouracil and its prodrugs. The chemistry and chemotherapeutic potential of TP/PD-ECGF inhibitors are also discussed.

The essential schizosaccharomyces pombe cdc23 DNA replication gene shares structural and functional homology with the Saccharomyces cerevisiae DNA43 (MCM10) gene.

The fission yeast cdc23 gene is required for correct DNA replication: cdc23 mutants show reduced rates of DNA synthesis and become elongated after cell-cycle arrest. We have cloned the Schizosaccharomyces pombe cdc23 gene by complementation of the temperature-sensitive phenotype of cdc23-M36 and confirmed the identity of the gene by integrative mapping. Analysis of the DNA sequence reveals that cdc23 can encode a protein of 593 amino acids (Mr=67 kDa) with 22% overall identity and many structural homologies with the product of the Saccharomyces cerevisiae DNA43 (MCM10) gene which is required for correct initiation of DNA synthesis at chromosomal origins of replication. Construction of a cdc23 null allele has established that the cdc23 gene is essential for viability, with cdc23 deletion mutant spores germinating but undergoing arrest with undivided nuclei in the first or second cell cycle. The S. pombe cdc23 gene on an expression plasmid is able to complement the S. cerevisiae dna43-1 mutant. These structural and functional homologies between two distantly related species suggest that cdc23 and DNA43 may represent genes for a conserved essential eukaryotic DNA replication function.

The rupture rate of acute flexor tendon repairs mobilized by the controlled active motion regimen.

A series of 233 patients with complete divisions of flexor tendons in zones 1 and 2 underwent operation following emergency admission over a period of 3.5 years. These included 203 patients with 317 divided tendons in 224 fingers injuries in zones 1 and 2 and 30 patients with 30 complete divisions of the flexor pollicis longus tendon in zones 1 and 2. All of these patients were mobilized post-operatively in a controlled active motion regimen. 13 (5.8%) fingers and five (16.6%) thumbs suffered tendon rupture during the post-operative period. Patients treated during the last year of the study were followed prospectively for a minimum period of 3 months; ten of the 16 (62.5%) fingers with zone 1 repairs, 50 of the 63 (79.4%) fingers with zone 2 repairs, all three (100%) FPL divisions in zone 1 and three of four (75%) FPL divisions in zone 2 had good and excellent results on assessment by the original Strickland criteria (Strickland and Glogovac, 1980). These results confirm the safety of this regimen as an alternative to other regimens of post-operative flexor tendon repair mobilization in zone 1 and 2 finger injuries. However, in the unmodified form used in this series, this regimen has too high a rupture rate for FPL mobilization.