Laparoscopic inguinal hernia repair with extraperitoneal double-mesh technique.

Totally extraperitoneal laparoscopic hernia repair is an efficient but technically demanding procedure. As mechanisms of hernia recurrence may be related to these technical difficulties, we have modified a previously described double-mesh technique in an effort to simplify the procedure. Extraperitoneal laparoscopic hernia repairs were performed in 82 male and 17 female patients having inguinal, femoral, and recurrent bilateral hernias. A standard propylene mesh measuring 15 x 15 cm was cut into two pieces of 4 x 15 cm and 11 x 15 cm. The smaller mesh was placed over both inguinal rings without splitting. The larger mesh was then inserted over the first mesh and stapled to low-risk zones, reinforcing the large-vessel area and the nerve transition zone. The mean procedure duration was 60 minutes for unilateral and 100 minutes for bilateral hernia repair. Patients were discharged from the hospital within 48 hours. The mean postoperative follow-up was 22 months, with no recurrences, neuralgia, or bleeding complications. Over a 2-year period, this technique was found to be satisfactory without recurrences or significant complications. In our hands, this technique was easier to perform: it allows for a less than perfect positioning of the meshes and avoids most of the stapling to crucial zones.

MACROPHAGES FROM CROHN'S DISEASE PATIENTS EXHIBIT DEFICIENT REPAIR FUNCTIONS

AbstractBackground: Mucosal healing is becoming a major goal in the treatment of Crohn's disease. It has been previously reported that myeloid cells induce mucosal healing in a mouse model of acute colitis. The aim in this study is to investigate the pro-repair function of myeloid cells in healthy donors (HD) and Crohn's disease patients (CD).Methods: Peripheral blood mononuclear cells (PBMC) from HD and CD patients were isolated from blood samples and tested either directly or after differentiation ex-vivo into macrophages (Μφ). Intestinal macrophages (IMACs) were isolated from the bowel mucosa of patients undergoing intestinal surgical resections. Through an in vitro wound healing assay the repairing ability of these various human myeloid cells and the mechanisms responsible of wound healing were evaluated.Results: PBMC and myeloid CD14+ cells from HD and CD were not able to repair at any tested cell concentration. Μφ from HD and ulcerative colitis (UC) patients were able to induce wound healing and this capacity was partially mediated by Hepatocyte Growth Factor (HGF). Remarkably, CD Μφ were unable to promote wound healing and produced lower levels of HGF as compared to Μφ from HD or UC patients. In particular, Μφ from CD in active phase (ACD) exhibited the weakest repair function, but this defect was rescued if rh- GM-CSF was added during the differentiation of PBMCs. Interestingly, IMACs from HD promoted wound healing and produced HGF.Conclusion: We demonstrated that CD Μφ, unlike HD or UC Μφ, were defective in promoting wound healing, in particular if coming from an ACD. This deficient pro-repair function was related to a lower production of HGF. IMACs from HD colonic mucosa induced wound healing, confirming the results obtained with Μφ. Our results are in keeping with the current theory of CD as an innate immunodeficiency. In this context, Μφ may be responsible for the mucosal repair defects observed in CD patients and for the subsequent chronic activation of the adaptive immune response.

Repair of tracheomalacia with inflammatory defect and mediastinitis.

We describe a novel repair of an anterior inflammatory tracheal defect with mediastinitis, which occurred after external tracheal suspension of localized intrathoracic tracheomalacia. The malacic tracheal segment of 4-cm length containing the inflammatory tracheal defect was noncircumferentially resected. A temporary endotracheal silicone stent was introduced, and the trachea was closed by a pedicled pectoralis muscle flap reinforced with an embedded rib segment. Retrieval of the stent 5 months postoperatively resulted in a re-epithelialized, persistently stable, noncollapsible tracheal segment that showed the same diameter and configuration as the nonreconstructed part of the trachea.

Direct Fourier Tomographic Reconstruction Image-To-Image Filter

We present an open-source ITK implementation of a directFourier method for tomographic reconstruction, applicableto parallel-beam x-ray images. Direct Fourierreconstruction makes use of the central-slice theorem tobuild a polar 2D Fourier space from the 1D transformedprojections of the scanned object, that is resampled intoa Cartesian grid. Inverse 2D Fourier transform eventuallyyields the reconstructed image. Additionally, we providea complex wrapper to the BSplineInterpolateImageFunctionto overcome ITKâeuro?s current lack for image interpolatorsdealing with complex data types. A sample application ispresented and extensively illustrated on the Shepp-Loganhead phantom. We show that appropriate input zeropaddingand 2D-DFT oversampling rates together with radial cubicb-spline interpolation improve 2D-DFT interpolationquality and are efficient remedies to reducereconstruction artifacts.

Early stage disc degeneration does not have an appreciable affect on stiffness and load transfer following vertebroplasty and kyphoplasty.

Vertebroplasty and kyphoplasty have been reported to alter the mechanical behavior of the treated and adjacent-level segments, and have been suggested to increase the risk for adjacent-level fractures. The intervertebral disc (IVD) plays an important role in the mechanical behavior of vertebral motion segments. Comparisons between normal and degenerative IVD motion segments following cement augmentation have yet to be reported. A microstructural finite element model of a degenerative IVD motion segment was constructed from micro-CT images. Microdamage within the vertebral body trabecular structure was used to simulate a slightly (I = 83.5% of intact stiffness), moderately (II = 57.8% of intact stiffness), and severely (III = 16.0% of intact stiffness) damaged motion segment. Six variable geometry single-segment cement repair strategies (models A-F) were studied at each damage level (I-III). IVD and bone stresses, and motion segment stiffness, were compared with the intact and baseline damage models (untreated), as well as, previous findings using normal IVD models with the same repair strategies. Overall, small differences were observed in motion segment stiffness and average stresses between the degenerative and normal disc repair models. We did however observe a reduction in endplate bulge and a redistribution in the microstructural tissue level stresses across both endplates and in the treated segment following early stage IVD degeneration. The cement augmentation strategy placing bone cement along the periphery of the vertebra (model E) proved to be the most advantageous in treating the degenerative IVD models by showing larger reductions in the average bone stresses (vertebral and endplate) as compared to the normal IVD models. Furthermore, only this repair strategy, and the complete cement fill strategy (model F), were able to restore the slightly damaged (I) motion segment stiffness above pre-damaged (intact) levels. Early stage IVD degeneration does not have an appreciable effect in motion segment stiffness and average stresses in the treated and adjacent-level segments following vertebroplasty and kyphoplasty. Placing bone cement in the periphery of the damaged vertebra in a degenerative IVD motion segment, minimizes load transfer, and may reduce the likelihood of adjacent-level fractures.

Revision anterior cruciate ligament reconstruction with quadriceps tendon-patellar bone autograft.

PURPOSE: To evaluate the cause of recurrent pathologic instability after anterior cruciate ligament (ACL) surgery and the effectiveness of revision reconstruction using a quadriceps tendon autograft using a 2-incision technique. TYPE OF STUDY: Retrospective follow-up study. METHODS: Between 1999 and 2001, 31 patients underwent ACL revision reconstruction because of recurrent pathologic instability during sports or daily activities. Twenty-eight patients were reviewed after a mean follow-up of 4.2 years (range, 3.3 to 5.6 years). The mean age at revision surgery was 27 years (range, 18 to 41 years). The average time from primary procedure to revision surgery was 26 months (range, 9 to 45 months). A clinical, functional, and radiographic evaluation was performed. Also magnetic resonance imaging (MRI) or computed tomography (CT) scanning was performed. The International Knee Documentation Committee (IKDC), Lysholm, and Tegner scales were used. A KT-1000 arthrometer measurement (MEDmetric, San Diego, CA) by an experienced physician was made. RESULTS: Of the failures, 79% had radiographic evidence of malposition of their tunnels. In only 6 cases (21%) was the radiologic anatomy of tunnel placement judged to be correct on both the femoral and tibial side. The MRI or CT showed, in 6 cases, a too-centrally placed femoral tunnel. After revision surgery, the position of tunnels was corrected. A significant improvement of Lachman and pivot-shift phenomenon was observed. In particular, 17 patients had a negative Lachman test, and 11 patients had a grade I Lachman with a firm end point. Preoperatively, the pivot-shift test was positive in all cases, and at last follow-up in 7 patients (25%) a grade 1+ was found. Postoperatively, KT-1000 testing showed a mean manual maximum translation of 8.6 mm (SD, 2.34) for the affected knee; 97% of patients had a maximum manual side-to-side translation <5 mm. At the final postoperative evaluation, 26 patients (93%) graded their knees as normal or nearly normal according to the IKDC score. The mean Lysholm score was 93.6 (SD, 8.77) and the mean Tegner activity score was 6.1 (SD, 1.37). No patient required further revision. Five patients (18%) complained of hypersensitive scars from the reconstructive surgery that made kneeling difficult. CONCLUSIONS: There were satisfactory results after ACL revision surgery using quadriceps tendon and a 2-incision technique at a minimum 3 years' follow-up; 93% of patients returned to sports activities. LEVEL OF EVIDENCE: Level IV, case series, no control group.

DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.

The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to ∼50% of the variation in both age at menarche and menopause, but to date the known genes explain <15% of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 × 10(-9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.

Method for retinal gene repair in neonatal mouse.

Gene correction at the site of the mutation in the chromosome is the absolute way to really cure a genetic disease. The oligonucleotide (ODN)-mediated gene repair technology uses an ODN perfectly complementary to the genomic sequence except for a mismatch at the base that is mutated. The endogenous repair machinery of the targeted cell then mediates substitution of the desired base in the gene, resulting in a completely normal sequence. Theoretically, it avoids potential gene silencing or random integration associated with common viral gene augmentation approaches and allows an intact regulation of expression of the therapeutic protein. The eye is a particularly attractive target for gene repair because of its unique features (small organ, easily accessible, low diffusion into systemic circulation). Moreover therapeutic effects on visual impairment could be obtained with modest levels of repair. This chapter describes in details the optimized method to target active ODNs to the nuclei of photoreceptors in neonatal mouse using (1) an electric current application at the eye surface (saline transpalpebral iontophoresis), (2) combined with an intravitreous injection of ODNs, as well as the experimental methods for (3) the dissection of adult neural retinas, (4) their immuno-labelling, and (5) flat-mounting for direct observation of photoreceptor survival, a relevant criteria of treatment outcomes for retinal degeneration.

A tailored approach for the treatment of indirect inguinal hernia in adults--an old problem revisited.

A patent processus vaginalis peritonei (PPV) presents typically as an indirect hernia with an intact inguinal canal floor during childhood. Little is known however about PPV in adults and its best treatment. A cohort study included all consecutive patients admitted for ambulatory open hernia repair. In patients with a PPV, demographics, hernia characteristics, and outcome were prospectively assessed. Annulorrhaphy was the treatment of choice in patients with an internal inguinal ring diameter of < 30 mm. Between 1998 and 2006, 92 PPVs (two bilateral) were diagnosed in 676 open hernia repairs (incidence of 14%). Eighty nine of the 90 patients were males, the median age was 34 years (range: 17-85). A PPV was right-sided in 67% and partially obliterated in 66%. Forty-one patients had an annulorrhaphy and 51 patients had a tension-free mesh repair. The median operation time was significantly shorter in the annulorrhaphy group (38 vs. 48 min, P <.0001). In a median follow-up period of 56 months (27-128), both groups did not differ concerning recurrence (1/41 vs. 2/51), chronic pain (3/41 vs. 4/51), and hypoesthesia (5/41 vs. 9/51). There was however a clear trend to less neuropathic symptoms in favor of annulorrhaphy (0/41 vs. 5/51, P < 0.066). PPV occurs in 14% of adults undergoing hernia repair. In selected patients, annulorrhaphy takes less time and is associated with equally low recurrence but less potential for neuropathic symptoms.

An EORTC phase I itudy of bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer.

The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still a reference regimen in advanced colorectal cancer; however, the addition of new biologic compounds represents a significant way forward. Bortezomib is an inhibitor of proteasome, a multicatalytic enzyme complex that degrades several intracellular proteins. In this study, escalating doses of Bortezomib were administered along with the standard FOLFOX-4 doses, in order to evaluate the dose-limiting toxicity (DLT), toxicity profile and activity of the combination. Patients with advanced colorectal cancer, unpretreated for metastatic disease, were enroled in the study. Bortezomib starting dose was 1.3mg/m(2), which was to be escalated in the subsequent steps according to the toxicities observed after first cycle. Exploratory pharmacogenetics research was conducted by analysing the association between clinical outcomes and polymorphisms in candidate genes for response to each of the used drugs. Correlation between tumour marker changes and response was also investigated. One mg/m(2) (DL-1) was defined as being the maximum tolerated dose since only 1 DLT was observed in 6 patients. The main toxicities were haematologic, neuropathy, diarrhoea and fatigue. Amongst 13 evaluable patients, five had a partial response, five had a stable disease and three patients progressed. Two patients are long-term survivors after a combined chemosurgical approach. Further trials of the current combination may be justified.

Transolecranon anterior fracture dislocation.

Between January 1996 and July 2003, 93 consecutive patients operated on with a diagnosis of olecranon fractures were identified from our trauma unit files. Fourteen transolecranon fracture-dislocations were found after a retrospective X-radiographic evaluation. Eight patients were women and six were men, with a mean age of 54 years. There were 4 noncomminuted olecranon fractures, treated with K-wires and single tension-band wiring. The remaining 10 fractures were complex fractures, treated in 3 cases with multiple K-wires and single tension-band wiring, in 2 by use of one-third tubular plates, in 1 with a 3.5-mm dynamic compression plate, and in the remaining 4 with 3.5-mm reconstruction plates. Ligament repair was not performed in any case. Three patients needed reoperation because of early failure of primary fixation. Patients were reviewed at a mean follow-up of 3.6 years. Two reported difficulties in daily activities, none with any symptoms of elbow instability. According to the Broberg and Morrey score, 4 patients had excellent results, 6 had good results, 2 had fair results, and 2 had poor results. Four patients showed signs of degenerative arthritis on the radiographs obtained at follow-up. We conclude that transolecranon fracture-dislocation is an underreported and misdiagnosed injury. Various fixation techniques can restore the anatomic relationships and contour of the trochlear notch; the imperative goal is to obtain a good stable primary fixation and allow early active mobilization.

3D reconstruction and comparison of shapes of DNA minicircles observed by cryo-electron microscopy.

We use cryo-electron microscopy to compare 3D shapes of 158 bp long DNA minicircles that differ only in the sequence within an 18 bp block containing either a TATA box or a catabolite activator protein binding site. We present a sorting algorithm that correlates the reconstructed shapes and groups them into distinct categories. We conclude that the presence of the TATA box sequence, which is believed to be easily bent, does not significantly affect the observed shapes.

Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep.

Previous studies support resorbable biocomposites made of poly(L-lactic acid) (PLA) and beta-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used beta-TCP bone substitute (ChronOS, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point.

Free conjunctival autologous graft for bleb repair and bleb reduction after trabeculectomy and nonpenetrating filtering surgery.

PURPOSE: To describe methods and outcomes of excisional revision of a filtering bleb (bleb revision) using free conjunctival autologous graft either for bleb repair or for bleb reduction after trabeculectomy and deep sclerectomy with an implant. METHODS: Retrospective medical records were reviewed for a consecutive non-comparative case series comprising patients who underwent excisional revision of a filtering bleb between May 1998-January 2001. Excisional revision using free conjunctival autologous graft (bleb revision) was performed either for bleb repair, to treat early and late leaks and hypotony with maculopathy, or for bleb reduction, to improve ocular pain, discomfort, burning, foreign body sensation, tearing, and fluctuations of visual acuity. The revision consisted of bleb excision and free conjunctival autologous graft. The bleb histopathology was analyzed in patients who underwent bleb repair. RESULTS: Sixteen patients were included in the study, consisting of nine patients who had a trabeculectomy and seven patients who had a deep sclerectomy with an implant. Bleb revision was necessary in 14 patients due to leaking filtering bleb (bleb repair), and in 2 patients due to bleb dysesthesia (bleb reduction). After a follow-up of 15.1 +/- 8.4 months, the mean intraocular pressure (IOP) rose from 7.8 +/- 6.3 mm Hg to 14.3 +/- 6.5 mm Hg, and the visual acuity from 0.4 +/- 0.3 to 0.7 +/- 0.3, with a P value of 0.008 and 0.03, respectively. The complete success rate at 32 months, according to the Kaplan-Meier survival curve, was 38.3%, and the qualified success rate was 83.3%. Four patients (25%) required additional suturing for persistent bleb leak. To control IOP, antiglaucoma medical therapy was needed for six patients (37.5%) and repeated glaucoma surgery was needed for one patient. CONCLUSION: Free conjunctival autologous graft is a safe and successful procedure for bleb repair and bleb reduction. However, patients should be aware of the postoperative possibility of requiring medical or surgical intervention for IOP control after revision.

Neutron structure of type-III antifreeze protein allows the reconstruction of AFP-ice interface.

Antifreeze proteins (AFPs) inhibit ice growth at sub-zero temperatures. The prototypical type-III AFPs have been extensively studied, notably by X-ray crystallography, solid-state and solution NMR, and mutagenesis, leading to the identification of a compound ice-binding surface (IBS) composed of two adjacent ice-binding sections, each which binds to particular lattice planes of ice crystals, poisoning their growth. This surface, including many hydrophobic and some hydrophilic residues, has been extensively used to model the interaction of AFP with ice. Experimentally observed water molecules facing the IBS have been used in an attempt to validate these models. However, these trials have been hindered by the limited capability of X-ray crystallography to reliably identify all water molecules of the hydration layer. Due to the strong diffraction signal from both the oxygen and deuterium atoms, neutron diffraction provides a more effective way to determine the water molecule positions (as D(2) O). Here we report the successful structure determination at 293 K of fully perdeuterated type-III AFP by joint X-ray and neutron diffraction providing a very detailed description of the protein and its solvent structure. X-ray data were collected to a resolution of 1.05 Å, and neutron Laue data to a resolution of 1.85 Å with a "radically small" crystal volume of 0.13 mm(3). The identification of a tetrahedral water cluster in nuclear scattering density maps has allowed the reconstruction of the IBS-bound ice crystal primary prismatic face. Analysis of the interactions between the IBS and the bound ice crystal primary prismatic face indicates the role of the hydrophobic residues, which are found to bind inside the holes of the ice surface, thus explaining the specificity of AFPs for ice versus water.