Biomedical subjects

M Saleh

Publications and source records attributed to M Saleh.

At least 37 records · Page 2Linked to original sources

PubMed2001

Fine wire frame arthrodesis for the salvage of severe ankle pathology.

Ankle arthrodesis is an accepted method of treatment for severe ankle pathology, but no single method of treatment is universally successful. Compression is usually applied across the ankle joint and maintained with either internal or external fixation; both are associated with complications such as infection, non-union and pain. We present our experience of 13 difficult cases managed by fine wire external frames, and describe the surgical technique used.A sound arthrodesis was achieved in 12 out of 13 cases, though one case required a repeat procedure, giving a union rate of 92% of cases or 86% of procedures. The mean period of fixation was 24 weeks (range 12-82), followed by a mean period of cast immobilisation of 7 weeks (range 0-10). Using Mazur's functional ankle score there were seven good results, four fair, one poor and one failure, which resulted in a below knee amputation. We believe this method represents a significant improvement on previously published results, but accept that it requires considerable experience and should not be considered for primary ankle arthrodesis. We would recommend its usage for the salvage of failed arthrodesis or severe fracture non-union, particularly in the presence of infection.

Adult↗

PubMed2001

The use of trans-articular and extra-articular external fixation for management of distal tibial intra-articular fractures.

Twenty-nine consecutive cases of distal tibial intra-articular fractures treated by trans-articular or extra-articular external fixation techniques have been reviewed. Eleven cases were treated initially with a trans-articular dynamic axial fixator. Of these seven were converted to an extra-articular SHF, for a combination of poor ankle motion and delayed healing of the metaphyseo-diaphyseal dissociation (MDD). Three of these cases (two patients) required bone grafting for delayed healing of the diaphyseal component of the fracture. Apart from one refracture through the MDD, no major complications were seen. No deep infections and no angular malalignments were noted. There were 11 pin track infections. Subjective assessment using short form-36 (SF-36) questionnaires, however, revealed significant differences compared to a normal population particularly in physical function and pain at a mean follow-up of 21 months. Using Bone's criteria for assessment of range of motion there were 62% excellent and good results, which dropped to 53% when fractures with a metaphyseo-diaphyseal extension were included. The use of minimally invasive techniques of internal fixation and stabilisation with a Sheffield hybrid frame in the management of distal tibial intra-articular fractures has minimal complications. Trans-articular external fixation is a good primary treatment for badly comminuted articular fractures with poor soft tissue condition. Conversion to extra-articular external fixation is recommended for slower healing fractures allowing ankle movement and early weight-bearing. The presence of a MDD dissociation lengthens the treatment time significantly, adds to the morbidity and affects final outcome.

Adult↗

PubMed2001

Management of non-unions with mono-lateral external fixation.

UNLABELLED: We reviewed a cohort of 107 patients (110 long bone segments) with fracture non-union, treated by mono-lateral external fixation in Sheffield between 1987 and 1996. There were 83 males and 24 females with a mean age of 36 years. Sixty-seven patients had high-energy injuries and there were 56 open fractures. There were 60 tibiae, 38 femora and the rest were upper limb long bones with a mean of 3.2 previous procedures. The mean duration of non-union was 23.4 months (range 3-123). There were 61 mono-focal procedures with 41 supported in neutralisation, 20 in compression and three in distraction. There were 49 bifocal procedures (33 compression distraction and 16 bone transport). Seventy-one segments required a bone graft. The success rate using the initial fixator was 90%. Seven patients required further fixation to achieve clinical and radiological union, bringing the healing rate to 95.5% (total n=105). There were five amputations, all in smokers and three of them were directly related to vascular failure. The mean hospital stay was 21 days and the mean number of operations per patients was 2.55. The mean time to bony union was 12.69 months (range 2.5-64). The mean length gain was 4.5 cm (range 1.5-12 cm), the mean angular correction achieved was 12 degree (range 2-39 degree). The bony and functional results were assessed at the end of treatment by system described by Paley and Catagni (JBJS 77A, 1995). CONCLUSIONS: Mono-lateral external fixation can provide stable fixation for the treatment of established non-unions. The fracture environment may be carefully controlled and angulation and length corrected simultaneously. Interestingly 11 out of 12 problem cases were in smokers.

Adolescent↗

PubMed2001

Bicondylar tibial plateau fractures managed with the Sheffield Hybrid Fixator. Biomechanical study and operative technique.

The two main challenges in the management of bicondylar tibial plateau fractures are: Firstly, the compromised skin and soft tissue envelope which invite a high rate of complications following attempted open reduction and dual plating. Secondly, poor bone quality and comminuted fracture patterns, which create difficulty in achieving stable fixation. Although dual plating is considered to be the best mechanical method of stabilizing these complex fractures, there remains concern regarding the high rate of complications associated with extensive soft tissue dissection, required for the insertion of these plates in an already compromised knee. The Sheffield Hybrid fixator (SHF) technique offers a solution to the two main problems of these difficult fractures by minimizing soft tissue dissection, since bone fragments are reduced and fixed percutaneously, and providing superior cancellous bone purchase with beam loading stabilization for comminuted fractures. Our biomechanical testing showed the SHF with four tensioned wires to be as strong as dual plating and able to provide adequate mechanical stability in the fixation of bicondylar tibial plateau fractures. This was confirmed clinically by a prospective review of the use of the SHF at our centre, for managing complex and high-energy tibial plateau fractures with a good final outcome and no cases of deep infection or septic arthritis.

Adolescent↗

PubMed2001

The Sheffield hybrid fixator--a clinical and biomechanical review.

The Sheffield hybrid fixator (SHF) was developed to complement and extend the use of current monolateral fixation systems. Unlike other hybrid designs, it relies on rings for the diaphyseal as well as the metaphyseal support. Since it is an all ring system it may be used to cross joints and perform progressive deformity and contracture correction. Unlike the Ilizarov system only one ring is required at each level and diaphyseal transfixation is avoided. Initial biomechanical testing has demonstrated similar mechanical characteristics to an all wire Ilizarov fixator, however, increased shear motion was noted due to the stiffness asymmetry between the segments controlled by wires and screws. The first 100 cases were reviewed with good patient compliance and satisfactory results. Minor component problems were identified and corrected during this period and no significant complications occurred. The device is recommended for a wide range of complex trauma and limb reconstruction uses.

Adult↗

PubMed2001

Fatigue testing median sternotomy closures.

OBJECTIVE: Sternal dehiscence is commonly due to wire cutting through bone. With a biological model, we measured the rate of cutting through bone, of standard steel wire closure, peristernal steel wire, figure-of-eight closure, polyester and sternal bands sternotomy closure techniques. METHODS: Polyester, figure-of-eight, peristernal and sternal band closures were tested against standard closure eight times using adjacent paired samples, to eliminate biological variables. Fatigue testing was performed by a computerized materials-testing machine, cycling between loads of 1 and 10 kg. The displacements at maximum and minimum loads were measured during each cycle. Cutting through, manifested by the displacement at the maximum load between the 1st and 150th cycles was measured. The percentage cut-through of each closure method versus standard closure was calculated. RESULTS: The differences in the displacement between each of the polyester (1.01 mm), figure-of-eight (0.52 mm), peristernal (0.72 mm) and sternal band (0.66 mm) groups versus standard closure (0.22, 0.22, 2.1, 3.2 mm) in the paired samples were statistically significant (Student's paired t-test; P<0.01). There were statistically significant differences in the percentage cut-through of polyester, figure-of-eight, peristernal and sternal bands (ANOVA, P<0.001), versus standard closure. CONCLUSIONS: In our sheep sternum model, we have quantified the differing rate of cutting through bone of five types of median sternotomy closure techniques. We have controlled for bone variables by testing each closure versus standard closure using paired adjacent bone samples. Peristernal and sternal band closure techniques are significantly superior to standard closure. The use of polyester and figure-of-eight closures requires caution.

Analysis of Variance↗

PubMed2001

Clearing of cells bearing the bcl-2 [t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy.

PURPOSE: Patients who were PCR-positive for B-cell leukemia-lymphoma 2 (bcl-2) gene rearrangement [t(14;18)] were evaluated for responses to rituximab alone or combined with CHOP. PATIENTS AND METHODS: Patients had relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (IWF: A-D). The single-agent trial used 375 mg/m2 weekly x 4; combination therapy included six cycles of CHOP and six 375 mg/m2 infusions of rituximab. Bcl-2 analyses of bone marrow (BM) and peripheral blood (PB) samples at base-line and following therapy were performed using a PCR assay. RESULTS: In the single-agent trial, of 70 patients whose peripheral blood (PB) was bcl-2 positive at baseline, 36 became bcl-2-negative, 13 remained positive, and 21 varied between positive and negative. The overall response rates (ORRs) were 72%, 31%, and 57%, respectively. Twelve of twenty-two patients with repeat bone marrow (BM) samples were bcl-2-negative three months post-treatment. Of 18 patients in the combination trial, 8 were bcl-2 positive in PB and/or BM. All of seven patients positive in PB at baseline and six of seven patients positive in BM were negative at the end of therapy; all patients responded to treatment (100% ORR). CONCLUSIONS: Rituximab, alone or combined with CHOP, eradicated bcl-2 positive cells from PB and BM in over half of the patients treated and was associated with a high overall clinical response rate. The impact on disease-free and overall survival awaits long-term follow up.

Adult↗

PubMed2001

Assessment of Ilizarov correction of club-foot deformity using pedobarography. A preliminary report.

Relapsed congenital talipes equinovarus is difficult to assess and treat. Pedobarography provides dynamic measurement of the pressures under the foot, and may be used in the assessment of these patients both before and after operation. Our findings showed a statistically significant difference in the distribution of pressure across the foot after treatment by the Ilizarov technique.

Adolescent↗

PubMed2001

Fibula pseudarthrosis revisited treatment with Ilizarov apparatus: case report and review of the literature.

A case of isolated congenital fibula pseudarthrosis with progressive valgus ankle deformity is reported. Valgus deformity can be corrected early by Ilizarov apparatus. Bone grafting is an essential part of treatment for union of the pseudarthrosis site. Internal splinting may be helpful in preventing further valgus deformity by maintaining continuity of fibula. Age of presentation has an important bearing on the choice of treatment.

Ankle Joint↗

PubMed2000

A conformational change in PBX1A is necessary for its nuclear localization.

The fly homeodomain (HD) protein EXTRADENTICLE (EXD) is dependent on a second HD protein, HOMOTHORAX (HTH), for nuclear localization. We show here that in insect cells the mammalian homolog of EXD, PBX1A, shows a similar dependence on the HTH homologs MEIS1, 2, and 3 and the MEIS-like protein PREP1. Paradoxically, removal of residues N-terminal to the PBX1A HD abolishes interactions with MEIS/PREP but allows nuclear accumulation of PBX1A. We use deletion mapping and fusion to green fluorescent protein to map two cooperative nuclear localization signals (NLSs) in the PBX HD. The results of DNA-binding assays and pull-down experiments are consistent with a model whereby the PBX N-terminus binds to the HD and masks the two NLSs. In support of the model, a mutation in the PBX HD that disrupts contact with the N-terminus leads to constitutive nuclear localization. The HD mutation also increases sensitivity to protease digestion, consistent with a change in conformation. We propose that MEIS family proteins induce a conformational change in PBX that unmasks the NLS, leading to nuclear localization and increased DNA-binding activity. Consistent with this, PBX1 is nuclear only where Meis1 is expressed in the mouse limb bud.

Amino Acid Sequence↗

PubMed2000

Treatment of isolated complex distal femoral fractures by external fixation.

Thirteen patients with isolated distal femoral fractures were treated by external fixation. There were seven males and six females with an average age of 45 years. Four were Type A3 fractures, one Type C1, five Type C2 and three Type C3 fractures. Seven of these were open. In seven cases the articular surface was first reduced and fixed. The fixation was extended across the knee to supplement the distal fixation in six severe cases. The average follow up was 30 months. There was one non-union in the study with the average time to union in the other patients being six months. Using the Mize criteria for assessing clinical results we found that nine patients obtained a good to excellent score and four were classed as failures. The average range of movement of the knee in the study was 100 degrees. Apart from the single non-union all the fractures healed and there were no other serious complications. Considering the severity of the fractures we did not find any evidence to suggest that temporary fixation of the lateral soft tissues by fixator pins was detrimental. The results suggest that external fixation may be used to treat these difficult fractures without the risk of serious complications.

Adult↗

PubMed2000

The treatment of established intracranial tumors by in situ retroviral IFN-gamma transfer.

Current treatments for malignant gliomas are still largely ineffective in significantly improving prognosis. We have investigated the efficacy of treating established rat C6 glioma by in situ retroviral delivery of IFN-gamma cDNA. Ecotropic retrovirus packaging cells were transfected with a retroviral vector containing the mouse IFN-gamma gene. The IFN-gamma packaging cells were stereotactically implanted into established intracranial C6 glioma in immunocompetent Wistar rats, resulting in the eradication of these tumors. All IFN-gamma-treated rats survived to 92 days after C6 implantation (an arbitrary end point) compared with 14 days for controls. Analysis of these treated brains showed that the established C6 tumors had been completely eradicated by this time-point with brain morphology appearing normal. The IFN-gamma-mediated tumoricidal activity resulted from an apparent interplay of B and T cell components of the immune system, as well as the inhibition of tumor angiogenesis. This therapeutic strategy may provide an effective method of eradicating established intracranial tumors.

Animals↗

PubMed2000

Cell signaling switches HOX-PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases.

The Hoxb1 autoregulatory element comprises three HOX-PBX binding sites. Despite the presence of HOXB1 and PBX1, this enhancer fails to activate reporter gene expression in retinoic acid-treated P19 cell monolayers. Activation requires cell aggregation in addition to RA. This suggests that HOX-PBX complexes may repress transcription under some conditions. Consistent with this, multimerized HOX-PBX binding sites repress reporter gene expression in HEK293 cells. We provide a mechanistic basis for repressor function by demonstrating that a corepressor complex, including histone deacetylases (HDACs) 1 and 3, mSIN3B, and N-CoR/SMRT, interacts with PBX1A. We map a site of interaction with HDAC1 to the PBX1 N terminus and show that the PBX partner is required for repression by the HOX-PBX complex. Treatment with the deacetylase inhibitor trichostatin A not only relieves repression but also converts the HOX-PBX complex to a net activator of transcription. We show that this activation function is mediated by the recruitment of the coactivator CREB-binding protein by the HOX partner. Interestingly, HOX-PBX complexes are switched from transcriptional repressors to activators in response to protein kinase A signaling or cell aggregation. Together, our results suggest a model whereby the HOX-PBX complex can act as a repressor or activator of transcription via association with corepressors and coactivators. The model implies that cell signaling is a direct determinant of HOX-PBX function in the patterning of the animal embryo.

Acetyltransferases↗

PubMed2000

Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas.

PURPOSE: This multicenter phase II study evaluated the efficacy, dosimetry methodology, and safety of iodine-131 tositumomab in patients with chemotherapy-relapsed/refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients received a dosimetric dose that consisted of 450 mg of anti-B1 antibody followed by 35 mg (5 mCi) of iodine-131 tositumomab. Serial total-body gamma counts were then obtained to calculate the patient-specific millicurie activity required to deliver the therapeutic dose. A therapeutic dose of 75 cGy total-body dose (attenuated to 65 cGy in patients with platelet counts of 101,000 to 149,000 cells/mm(3)) was given 7 to 14 days after the dosimetric dose. RESULTS: Forty-five of 47 patients were treated with a single dosimetric and therapeutic dose. Twenty-seven patients (57%) had a response. The response rate was similar in patients with low-grade (57%) or transformed low-grade (60%) NHL. The median duration of response was 9.9 months. Fifteen patients (32%) achieved a complete response (CR; 10 CRs and five clinical CRs), including five patients (50%) with transformed low-grade NHL. The median duration of CR was 19.9 months, and six patients have an ongoing CR. Treatment was well tolerated, with the principal toxicity being hematologic. The most common nonhematologic toxicities that were considered to be possibly related to the treatment included mild to moderate fatigue (32%), nausea (30%), fever (26%), vomiting (15%), infection (13%), pruritus (13%), and rash (13%). Additionally, one patient developed human-antimouse antibodies. CONCLUSION: Iodine-131 tositumomab produced a high overall response rate, and approximately one third of patients had a CR despite having chemotherapy-relapsed or refractory low-grade or transformed low-grade NHL.

Adult↗

PubMed2000

The expression of vascular endothelial platelet endothelial cell adhesion molecule-1 is not regulated by IFN-gamma treatment of C6 tumors in vivo.

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a glycoprotein that is constitutively expressed on the surface of endothelial cells, leukocytes, platelets, monocytes and neutrophils. It has been proposed that PECAM-1 plays a role in transendothelial leukocyte trafficking. In vitro studies have suggested that interferon-gamma (IFN-gamma) may regulate PECAM-1 expression on endothelial cells. We have investigated the in vivo regulatory role of mouse IFN-gamma (mIFN-gamma) on the expression of PECAM-1 on vascular endothelial cells during tumor angiogenesis. In situ retroviral gene transfer was used to deliver mIFN-gamma into established subcutaneous tumors in athymic (nu/nu) mice. The biological activity of mIFN-gamma expressed intratumorally, was verified by i) a macrophage and granulocyte (predominantly neutrophil) infiltrate observed within C6 tumors following mIFN-gamma treatment; ii) an up-regulation of major histocompatibility complex (MHC) class I and II expression on the surface of tumor cells following mIFN-gamma treatment. Indirect immunohistochemical localisation of PECAM-1 expression was performed on control and mIFN-gamma-treated C6 tumor sections. The intensity and distribution of PECAM-1 expression on vascular endothelial cells in mIFN-gamma-treated tumors was similar to control tumors. Immunohistochemical staining of PECAM-1 was compared to factor VIII-related antigen in serial tumor sections. No differences were observed between the vascular endothelial cells expressing PECAM-1 and factor VIII in serial sections of control and mIFN-gamma-treated tumors. Therefore, in this in vivo C6 tumor model, IFN-gamma does not alter PECAM-1 expression on tumor-associated vascular endothelial cells.

Animals↗

PubMed1999

Effect of in situ retroviral interleukin-4 transfer on established intracranial tumors.

BACKGROUND: Current therapies for malignant gliomas remain largely ineffective. We have previously demonstrated that interleukin 4 (IL-4) exhibits antitumorigenic activity in athymic nude mice by promoting both eosinophil infiltration and inhibition of tumor angiogenesis (formation of new blood vessels). In this study, we investigated treatment of established rat C6 cell gliomas by retroviral delivery of IL-4 in situ. METHODS: Tumors grown subcutaneously in athymic nude mice or implanted intracranially in immunocompetent Wistar rats were implanted with ecotropic retrovirus (i.e., will replicate only in cells of closely related species) packaging cells (RPCs) that were transfected with a retroviral vector encoding mouse IL-4 (1C5 cells) or a control vector (SV cells). For the demonstration of the long-term effects of such treatment, C6 cells were also implanted into the contralateral hemisphere of the brains of rats previously treated with 1C5 RPCs. Tumor volume measurements and immunohistochemical analyses were performed. RESULTS: Implantation of 1C5 RPCs into subcutaneous C6 cell tumors resulted in tumor growth arrest that was associated with eosinophil infiltration and inhibition of angiogenesis. When 1C5 RPCs were stereotactically implanted into established intracranial tumors in rats, tumor volumes were dramatically smaller than in control animals (approximately 1.8 mm3 versus 70-80 mm3, respectively) 7 days after treatment. All 1C5 RPC-treated rats survived to 106 days after C6 cell implantation (99 days after treatment; an arbitrary end point), whereas control rats had to be killed 14 days after C6 cell implantation because of extensive tumor growth. Histologic analysis demonstrated that treated tumors were completely eradicated, and immunohistochemical analysis revealed an inhibition of tumor angiogenesis and infiltration by CD8+ cells and macrophages. C6 cells implanted contralaterally into the brains of long-term-surviving rats treated with 1C5 RPCs were also rapidly and completely rejected. CONCLUSIONS: Implantation of packaging cells producing IL-4 retrovirus leads to rapid eradication of rat C6 cell gliomas and provides sustained protection against further intracranial challenge.

Animals↗

PubMed1999

Multinucleated giant cells in fine-needle aspiration of thyroid nodules: their diagnostic significance.

Multinucleated giant cells (MNGCs) are reported in many thyroid lesions. This study examines whether their quantity and quality can help in the differential diagnosis. All fine-needle aspirations (FNAs) of the thyroid with a "significant" number of MNGCs were reviewed from 1995 -1998. There were 23 cases (<1% of thyroid FNAs): 8 papillary carcinomas (PC), 4 subacute thyroiditis (ST), 3 granulomas, 7 adenomatous goiters (AG), and one Hurthle-cell adenoma (HA). MNGCs with dense cytoplasm were seen exclusively in PC, ST, and granulomas. They had angulated shapes. They were most numerous, largest, and with the highest number of nuclei in ST and granulomas. MNGCs with foamy cytoplasm were seen in AG and HA and 80% of the other cases (PC, ST, and granulomas). In PC, rare MNGCs had intranuclear inclusions and grooves. The accompanying cell population was characteristic of each disease. The quantity and quality of MNGCs in thyroid FNA may be helpful in narrowing the differential diagnosis. Diagn. Cytopathol. 1999;21:307-312.

Adenoma↗

PubMed1999

An open fracture of the ulna with bone loss, treated by bone transport.

We report a Gustilo and Anderson IIIc fracture of the ulna with 8 cm of bone loss which was reconstructed primarily by the technique of external fixation and bone transport. Five operations were performed over a period of 14 months (treatment index = 52.5 days/cm). A satisfactory functional result was achieved, demonstrating the efficacy of this technique for difficult forearm reconstructions and comparing favourably with other methods of managing large bone and soft tissue defects.

Adult↗