Biomedical subjects

M Saleh

Publications and source records attributed to M Saleh.

At least 55 records · Page 3Linked to original sources

PubMed1999

Peri operative ultrasound guided needle localisation of amputation stump neuroma.

Ten patients with clinically suspected neuromas following amputation were submitted for ultrasound examination. Neuromas in seven of the ten patients were identified as the cause of pain with ultrasound guided infiltration of local anaesthetic. Pre operative localisation, using breast localisation wires allowed the neuromas to be surgically excised with reduced dissection. This small study demonstrates that ultrasound is an effective method for identifying and localising neuromas in amputation stumps. This leads to reduced dissection and may lead to a better outcome in these patients.

Adult↗

PubMed1999

A biomechanical study of median sternotomy closure techniques.

OBJECTIVE: Sternal dehiscence is a complication of median sternotomy incisions with high mortality and morbidity. Different techniques of sternal closure have been described. Rigid fixation of the sternum results in earlier union. We measured the rigidity of sternotomy fixation using a mechanical model in order to differentiate different techniques of sternal closure using their biomechanical characteristics. METHODS: We measured the force-displacement curves of six different fixation techniques using a metal sternal model using a computerized materials-testing machine. We tested straight wires (the most commonly used surgical technique), figure-of-8 wires, 'repair' technique (used when a wire breaks), Ethibond, Sterna-band and a 'multitwist' closure described for the first time. RESULTS: At 20 kg force, twisted wires used for sternotomy closures start to untwist. The most rigid closure was a multitwist closure that displaced only 0.37 mm at a force of 20 kg. Straight wires displaced 0.78 mm, figure-of-8 wires 1.20 mm, Sterna-band 1.37 mm, repair wires 5.08 mm, Ethibond 9.37 mm. The single factor Anova test for the rigidity of the different closures had P-values <0.0001. CONCLUSIONS: We applied a mathematical model to calculate chest wall forces during coughing, in order to determine the force placed upon a sternotomy closure. We conclude that severe coughing may cause wires to untwist. We discuss potential applications of different wire closures based on their characteristics.

Biomechanical Phenomena↗

PubMed1999

Psychological adjustment of children awaiting limb reconstruction treatment.

The psychological profiles of 53 children aged 6-17 years, with congenital and acquired limb abnormalities attending a limb reconstruction centre, were examined to determine the level of need for pretreatment psychological intervention. The profiles of two groups presenting for treatment--patients of short stature and those with other limb abnormalities--were compared with each other and with general population norms. Standardized questionnaires were administered to patients and their parents during pretreatment assessment visits to the clinic. There were few differences between the families taking part in this study and the general population norms, or between the scores of children with short stature and those with other limb abnormalities. These results may indicate that most children awaiting limb reconstructive surgery are not in need of psychological intervention other than the support routinely offered. The findings are discussed in terms of the biases which may be reflected in the referral process, possible protective effects of family environment factors and clinical support systems, and the impact of the timing of the assessments. Implications for future research are discussed.

Adaptation, Psychological↗

PubMed1999

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy.

PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. PATIENTS AND METHODS: Forty patients with low-grade or follicular B-cell non-Hodgkin's lymphoma received six infusions of Rituxan (375 mg/m2 per dose) in combination with six doses of CHOP chemotherapy. RESULTS: The overall response rate was 95% (38 of 40 patients). Twenty-two patients experienced a complete response (55%), 16 patients had a partial response (40%), and two patients, who received no treatment, were classified as nonresponders. Medians for duration of response and time to progression had not been reached after a median observation time of 29 + months. Twenty-eight of 38 assessable patients (74%) continued in remission during this median follow-up period. The most frequent adverse events attributable to CHOP were alopecia (38 patients), neutropenia (31 patients), and fever (23 patients). The most frequent events attributed to Rituxan were fever and chills, observed primarily with the first infusion. No quantifiable immune response to the chimeric antibody was detected. In a subset of 18 patients, the bcl-2 [t(14;18)] translocation was positive in eight patients; seven of these patients had complete remissions and converted to polymerase chain reaction (PCR) negativity by completion of therapy. CONCLUSION: This is the first report demonstrating the safety and efficacy of Rituxan anti-CD20 chimeric antibody in combination with standard-dose systemic chemotherapy in the treatment of indolent B-cell lymphoma. The clinical responses suggest an additive therapeutic benefit for the combination with no significant added toxicity. The conversion of bcl-2 from positive to negative by PCR in blood and/or marrow suggests possible clearing of minimal residual disease not previously demonstrated by CHOP chemotherapy alone.

Adult↗

PubMed1999

Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer.

PURPOSE: BMS-182248-1 (BR96-doxorubicin immunoconjugate) is a chimeric human/mouse monoclonal antibody linked to approximately eight doxorubicin molecules. The antibody is directed against the Lewis-Y antigen, which is expressed on 75% of all breast cancers but is limited in expression on normal tissues. Preclinical xenograft models demonstrated significant antitumor activity, including cures. A randomized phase II design was chosen to estimate the activity of the BR96-doxorubicin conjugate in metastatic breast cancer in a study population with confirmed sensitivity to single-agent doxorubicin. PATIENTS AND METHODS: Patients with measurable metastatic breast cancer and immunohistochemical evidence of Lewis-Y expression on their tumor received either BR96-doxorubicin conjugate 700 mg/m2 IV over 24 hours or doxorubicin 60 mg/m2 every 3 weeks. Patients were stratified on the basis of prior doxorubicin exposure, visceral disease, and institution. Cross-over to the opposite treatment arm was allowed with progressive or persistently stable disease. RESULTS: Twenty-three patients who had received a median of one prior chemotherapy regimen were assessable. There was one partial response (7%) in 14 patients receiving the BR96-doxorubicin conjugate and one complete response and three partial responses (44%) in nine assessable patients receiving doxorubicin. No patient experienced a clinically significant hypersensitivity reaction. The toxicities were significantly different between the two treatment groups, with the BR96-doxorubicin conjugate group having limited hematologic toxicity, whereas gastrointestinal toxicities, including marked serum amylase and lipase elevations, nausea, and vomiting with gastritis, were prominent. CONCLUSION: The BR96-doxorubicin immunoconjugate has limited clinical antitumor activity in metastatic breast cancer. The gastrointestinal toxicities likely represent binding of the agent to normal tissues expressing the target antigen and may have compromised the delivery of the immunoconjugate to the tumor sites.

Adult↗

PubMed1999

Limb reconstruction after high energy trauma.

Limb reconstruction techniques rely on stable external fixation to provide early limb function after major long bone injury. Bone may be generated by callus distraction techniques and internal techniques of moving bone segments used to fill bone defects. Soft tissue defects may be treated by acute shortening, although skin defects will also close spontaneously during bone transport as the leading edge of bone is covered with granulation tissue. External fixation is also used to cross joints permitting rest and repair of the joint. Hinges placed within the bars of the fixation frame may be used to correct deformities in the bone and soft tissue contractures using closed distraction techniques. These techniques are appropriate to metaphyseal fractures and diaphyseal fractures with bone loss. A major advantage is the lack of donor site morbidity, associated with skin flaps and large bone grafts. Acceptance of these techniques is growing whilst the methodology continues to improve. In more complicated cases, specialist training and dedicated hospital units with multidisciplinary support is desirable.

External Fixators↗

PubMed1999

Vascular complications of osteotomies in limb reconstruction.

Osteotomies are commonly carried out in orthopaedic surgery, particularly in limb reconstruction. Complications are uncommon provided that sufficient care is taken and a sound technique used. We describe three cases of formation of false aneurysm after osteotomy, with acute, delayed and asymptomatic onset. The diagnosis was supported by ultrasound investigation, and confirmed by angiography. Embolisation with coils was a successful method of treatment. We recommend a safe method of osteotomy with good bone exposure and adequate soft-tissue protection.

Adolescent↗

PubMed1998

Index finger lengthening by gradual distraction and bone grafting.

We present the case of an 18-year-old woman with a shortened right index finger. The digit was stabilized and lengthened a total of 18 mm by external fixation and iliac bone grafting. A distal interphalangeal fixed flexion deformity of 60 degrees was corrected with external fixation and intermedullary wiring.

Adolescent↗

PubMed1998

Mother's milk protein profile, a possible biomarker for human exposure to persistent insecticides.

The electrophoretic protein profile and residue levels of selected persistent insecticides were investigated in 160 mother's milk samples representing 20 different locations in Egypt. Nine major protein bands were detected in all of the samples. These protein bands were designated as lactoferrin, albumin, SIgA heavy chain, casein I, casein II, SIgA light chain, casein III, lysozyme and alpha-lactalbumin. Residue levels of DDT and its metabolites as well as lindane and its other hexachlorocyclohexane isomers were determined using electron capture gas chromatography and confirmed by gas chromatography/mass spectrometric analysis. Samples containing relatively higher residue levels of the DDT group (DDT, DDE and DDD) showed significant effects on the levels of lysozyme and alpha-lactalbumin bands relative to samples with low or no residue levels. On the other hand, the casein subunits were mostly affected by the residue levels of hexachlorocyclohexane isomers (alpha, beta, gamma and delta isomers). The two patterns showed characteristic dose response correlation suggesting that the protein profile of human milk may serve as a quick biomarker for exposure to persistent insecticides.

Albumins↗

PubMed1998

Early irreversible osteonecrosis versus transient lesions of the femoral condyles: prognostic value of subchondral bone and marrow changes on MR imaging.

OBJECTIVE: The purpose of this study was to determine the MR imaging features that enable differentiation between early irreversible osteonecrosis and transient lesions in nontraumatic lesions of the femoral condyle having the "bone marrow edema" pattern on MR imaging. MATERIALS AND METHODS: We reviewed 23 nontraumatic painful lesions of the femoral condyle in 23 patients (12 men and 11 women; mean age, 62 years). All patients had undergone radiography of the knee with findings that were normal or inconclusive. Also, all patients underwent MR imaging that revealed the bone marrow edema pattern in a condyle. Lesions observed after trauma, surgery, or glucocorticoid medication, or with epiphyseal collapse or degenerative joint disease on initial plain radiographs, were excluded from this study. Of the 23 lesions, 14 showed complete resolution (and were designated as transient epiphyseal lesions). The remaining nine lesions were irreversible and, on follow-up radiographic and MR imaging studies, evolved to collapsed osteonecrosis (and were designated as early osteonecrosis). The presence and size of the subchondral features observed by two radiologists on initial MR studies were compared for both irreversible and transient epiphyseal lesions. RESULTS: Initial MR imaging characteristics indicative of an early irreversible osteonecrosis included a subchondral area of low signal intensity on T2-weighted images with a thickness of more than 4 mm (sensitivity, 100% and 100%; specificity, 82% and 74% for the two observers) or a length of more than 14 mm (sensitivity, 89% and 88%; specificity, 93% and 87% for the two observers), focal epiphyseal contour depressions, and lines of low signal intensity located deep in the affected condyle. The extent of edema was similar for both transient epiphyseal lesions and early osteonecrosis. CONCLUSION: Careful assessment of MR imaging changes occurring in the subchondral area can enable confident differentiation between transient epiphyseal lesions and early irreversible osteonecrosis of the femoral condyle.

Bone Marrow↗

PubMed1998

Assessment of 99Tcm-tetrofosmin lung uptake: a modified method to avoid the contribution from high chest wall activity.

Evaluation of lung uptake during routine 99Tcm-tetrofosmin myocardial SPET (single photon emission tomography) studies may be hindered by substantial chest muscle uptake, particularly post-exercise. This study investigated this proposal and analysed the various components of chest activity that may add to the real lung uptake. Exercise SPET studies were performed on normal subjects using 99Tcm-tetrofosmin and compared with the results of 99Tcm-sestamibi and 201Tl studies. The chest to heart count ratio (CHR) was calculated from the anterior SPET projection and further subclassified into lung, anterior chest and posterior chest to heart ratios (LHR, AHR, PHR) from the left anterior oblique (LAO) projection. On post-exercise images, the 99Tcm-tetrofosmin CHR was significantly higher than that of 201Tl and 99Tcm-sestamibi. Both the 99Tcm-tetrofosmin AHR and PHR were higher than those of 201Tl and 99Tcm-sestamibi. However, the LHR was similar for all three radiopharmaceuticals. In contrast, the rest 99Tcm-tetrofosmin images differed little from the 201Tl and 99Tcm-sestamibi ones. Thus, 99Tcm-tetrofosmin lung uptake post-exercise should be interpreted with caution, as chest muscle uptake is higher than normal. A more accurate evaluation of 99Tcm-tetrofosmin lung uptake is achieved from the LAO projection, where the contribution from chest muscle counts is much less than in the routinely used anterior projection.

Adult↗

PubMed1997

The paracrine role of tumour-derived mIL-4 on tumour-associated endothelium.

Interleukin-4 (IL-4) has been demonstrated to possess anti-tumourigenic properties in vivo which is initially attributed to the infiltration of eosinophils proposed to occur by IL-4 binding to its receptors on endothelial cells, thereby mediating eosinophil adhesion. We have investigated whether the binding of IL-4 to receptors on endothelial cells could elicit other biological responses which may also play a role in tumour inhibition, such as angiogenesis. We have demonstrated that mouse IL-4 (mIL-4) down-regulates the expression of one of the receptors for VEGF, VEGF-R2, on endothelial cells in vitro. By generating stable transfectants of C6 glioma cells that express mIL-4 under a tetracycline-responsive promoter system, we were able to apply tight regulatory control of mIL-4 expression in vivo. Subcutaneous implantation of mIL-4/C6 cell lines in nu/nu mice revealed that tumour growth is inhibited by mIL-4 expression. mIL-4-expressing tumours were demonstrated to have a reduced level of vascularisation compared with controls, in addition to a high degree of eosinophil infiltration. Our results suggest that mIL-4 has bimodal biological roles in potentiating tumour inhibition in athymic mice: the suppression of angiogenesis and the augmentation of the host local immune response.

Animals↗

PubMed1997

A retroviral vector that allows efficient co-expression of two genes and the versatility of alternate selection markers.

pZIG(hGCSFR) is a retroviral vector that can co-express two genes and also provides alternative selection markers. This retroviral vector has been constructed to incorporate an internal ribosome entry site (IRES) element to co-express two exogenous genes in mammalian cells. Two marker/selection genes have been cloned into the vector that not only allow the efficiency of co-expression to be quantified but also provide versatility of selection criteria. A cDNA encoding the hGCSFR (signaling deficient) was cloned as the 5' cistron, and a gene encoding a neomycin-resistance and beta-galactosidase (beta geo) fusion protein was cloned as the 3' cistron. The two marker genes cloned in this retroviral vector allow the selection and isolation of mammalian cells following either transient (by fluorescence-activating cell sorting analysis of hGCSFR-positive cells) or stable (neomycin resistance) infection with the certainty that over 93% of clones will co-express both genes. This novel vector offers a versatile retroviral vector that can be potentially used in a wide range of gene therapy applications as the gene of interest can be coexpressed with either of the marker genes depending on whether the retroviral infection is to be performed in vitro, in vivo, or ex vivo.

3T3 Cells↗

PubMed1997

A novel gene therapy strategy for elimination of prostate carcinoma cells from human bone marrow.

We report a novel means to purge bone marrow of a specific subset of prostate carcinoma cells based on transductional and genetic selectivity. Using both adenovirus-polylysine-DNA complexes and E1A/B-deleted replication-deficient adenoviruses, we have demonstrated a transductional preference of these vectors for the prostate carcinoma cell lines DU 145, LNCaP, and PC-3 over primary human bone marrow cells and the leukemia cell line KG-1. We have also shown a genetic selectivity of an anti-erbB-2 intracellular single-chain antibody (sFv) encoding adenovirus, Ad21, for the erbB-2-positive prostate carcinoma cell lines DU 145 and LNCaP. Delivery of Ad21 resulted in cytotoxicity to the DU 145 and LNCaP, but not PC-3, cell lines and reduced the clonogenic capacity of DU 145 cells cultured alone or mixed with various ratios of irradiated human bone marrow. Finally, quantitative, competitive reverse transcription polymerase chain reaction (QC-RT-PCR) analysis demonstrated that Ad21 could effectively reduce DU 145 and erbB-2-positive primary prostate tumor contamination in bone marrow cultures. Delivery of Ad21 had no effect on the ability of progenitor cells to form colonies. These results suggest that an anti-erbB-2 sFv-encoding adenoviral vector is efficacious for removal of erbB-2-positive prostate carcinoma cells from human bone marrow, and demonstrates a novel method for ex vivo genetic purge of malignant cells from bone marrow for autologous bone marrow transplantation (ABMT) therapy.

Adenoviridae↗

PubMed1997

Fracture of the tibial diaphysis treated by external fixation and the axial alignment grid: a single surgeon's experience.

The results of tibial fracture fixation for 50 unstable closed and open fractures, using the dynamic axial fixator (DAF) and the limb axial alignment grid have been assessed both clinically and radiologically. Each patient has been carefully followed up in a dedicated clinic and each procedure was conducted or directly supervised by the senior author. All patients achieved union, although 16 per cent required a further procedure such as bone grafting or fibula osteotomy to secure this and a further 6 per cent were revised to intramedullary nails. There was a malunion rate of 16 per cent, but no patients requested further treatment for functional problems. The incidence of pin-site infection was 10.4 per cent, each patient taking responsibility for their own pin-site care. There were no deep infections. The results achieved in this series compare favourably with those of other treatment modalities for this fracture, which may often be difficult to manage. Given the stringent adherence to the important principles of fixator application and well supervised follow-up which are practised on this unit, we believe that the results as presented here may well represent the limit achievable with this device. Furthermore, the authors would recommend that the technique remains an important option in tibial fracture management, particularly for the unstable closed and open fractures.

Adolescent↗

PubMed1997

Acute carpal tunnel syndrome as a complication of oral anticoagulant therapy.

Acute carpal tunnel syndrome is well recognized in patients with haemophilia and conservative management with factor replacement and temporary splinting is recommended. There have, however, been very few reported cases of acute carpal tunnel syndrome as a complication of oral anticoagulant therapy. We describe such a case in a patient on long-term warfarin anticoagulation, drawing attention to particular features of the history and clinical findings. In contrast to previous reports, we recommend prompt decompression under local anaesthesia and continuation of the anticoagulant therapy.

Anticoagulants↗

PubMed1997

Interleukin-2 fusion protein: an investigational therapy for interleukin-2 receptor expressing malignancies.

DAB389IL-2 is an interleukin-2 receptor (IL-2R) specific fusion protein with a molecular weight of 58 kD containing the enzymatic and translocation domains of diphtheria toxin (DT) and human IL-2. This fusion protein is able to direct the cytocidal action of the DT enzymatic region only to cells which bear the IL-2R. The human IL-2R exists in three forms: low, intermediate and high affinity. The high-affinity form is believed to be the biologically relevant form on mature, activated T-lymphocytes, B-lymphocytes and monocytes. DAB389IL-2 is able to bind selectively to the high-affinity IL-2R in a concentration-dependent manner, and once bound is internalised via receptor-mediated endocytosis. Upon acidification of the formed vesicle, the enzymatic portion of the fusion protein is believed to pass into the cytosol where it ultimately inhibits protein synthesis by inactivation of elongation factor-2, resulting in cell death. The constitutive expression of the IL-2R on certain leukaemic and lymphomatous cells of T and B cell origin has been reported to occur in patients with chronic lymphocytic leukaemia, cutaneous T cell lymphoma (CTCL), Hodgkin's disease and non-Hodgkin's lymphomas (NHLs). A multicentre DAB389IL-2 dose-escalation study of patients with IL-2R expressing lymphomas has been conducted. A 10-fold range of doses were evaluated on a five-daily dose schedule. Patients received up to six courses, with an additional two courses permitted for patients with partial responses that appeared to be still improving after six courses. Most adverse experiences were transient and mild. Preliminary assessment of response indicated five complete responses (CR, duration ongoing at 20, 11, 7, 5 and 4 months) and seven partial responses (PR, duration 3-20 months) in the 35 patients with CTCL. One CR (duration > 20 months) in a patient with NHL (Lennett's lymphoma) and two PR (duration 9 and 2 months) in 17 patients with B-cell NHL have been observed. Based on the mode of action of DAB389IL-2, its safety profile, and the patient responses associated with the phase I/II clinical trials, a phase III programme in CTCL patients has been initiated and plans for additional trials in NHL patients are targeted for 1996.

Antineoplastic Agents↗

PubMed1997

Intravenous infusions of nifedipine: an alternative for the prevention of hypertension in eye surgery under local anesthesia.

In order to control critical rises of blood pressure during the peri-operative period in elderly hypertensive patients, the effectiveness of a continuous intravenous infusion of nifedipine was studied. In a double blind study, patients (n = 60) who underwent eye surgery under local anesthesia were divided randomly into three groups. Patients who were found to have 200 > SBP > 160 and 120 > DBP > 90 mmHg as the previous day of surgery, as well as patients who did not receive any anti-hypertensive treatment regimen during the last week before surgery, were selected. Five min before performing local anesthesia, a continuous infusion of nifedipine at two different rates of 0.65 mg/h and 1.25 mg/h, was administered in groups A and B respectively, whereas group C received a placebo. SBP, DBP and HR were recorded every 5 min. for an hour. Statistically significant differences among the profiles of the three groups were found. The control group had a higher SBP/DBP. None of the groups, showed significant changes in HR. In conclusion, the intravenous infusion of nifedipine in a dose 1.25 mg/h, seems to control the hypertensive phases of blood pressure, without dropping to any unduly low level, risking undesirable side effects in elderly hypertensive patients during perioperative period.

Aged↗