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J O'Byrne

Publications and source records attributed to J O'Byrne.

At least 19 recordsLinked to original sources
PubMed2006

BCP crystals increase prostacyclin production and upregulate the prostacyclin receptor in OA synovial fibroblasts: potential effects on mPGES1 and MMP-13.

OBJECTIVE: To investigate the potential involvement of prostacyclin in basic calcium phosphate (BCP) crystal-induced responses in osteoarthritic synovial fibroblasts (OASF). METHODS: OASF grown in culture were stimulated with BCP crystals. Prostacyclin production was measured by enzyme immunoassay. Expression of messenger RNA (mRNA) transcripts was assessed by real-time polymerase chain reaction (PCR). Expression of prostacyclin synthase (PGIS) and the prostacyclin (IP) receptor was measured. The effects of iloprost, a prostacyclin analogue, on expression of genes implicated in osteoarthritis such as microsomal prostaglandin E2 synthase 1 (mPGES1) and matrix metalloproteinases (MMPs) were also studied. FPT inhibitor II, a farnesyl transferase inhibitor, was used to antagonize iloprost-induced responses. RESULTS: BCP crystal stimulation led to a five-fold increase in prostacyclin production in OASF compared to untreated cells. This induction was attenuated by cyclooxygenase (COX)-2 and COX-1 inhibition at 4 and 32h, respectively. PGIS and IP receptor transcripts were constitutively expressed in OASF. BCP crystals upregulated IP receptor expression two-fold. While iloprost diminished BCP crystal-stimulated IP receptor upregulation, the inhibitory effect of iloprost was blocked by the farnesyl transferase inhibitor. In addition, iloprost upregulated mPGES1 and downregulated MMP-13 expression in BCP crystal-stimulated OASF, effects that were not influenced by the farnesyl transferase inhibitor. CONCLUSIONS: These data showed for the first time that BCP crystals can increase prostacyclin production and upregulate expression of the IP receptor in OASF. The potential of prostacyclin to influence BCP crystal-stimulated responses was supported by the effects of iloprost on the expression of the IP receptor, mPGES1 and MMP-13. These data demonstrate the potential involvement of prostacyclin in BCP crystal-associated osteoarthritis (OA) and suggest that inhibition of PG synthesis with non-steroidal anti-inflammatory drugs may have both deleterious and beneficial effects in BCP crystal-associated OA.

Calcium Phosphates↗
PubMed2004

Functional outcome of burst fractures of the first lumbar vertebra managed surgically and conservatively.

We retrospectively reviewed 31 neurologically intact patients with burst L1 fractures. We obtained a follow-up clinical evaluation after a mean of 43 (14-80) months from 26 patients--11 treated surgically and 15 managed non-surgically. Patients were assessed with regard to pain, employment status, recreational activities and overall satisfaction. At final follow-up of 15 patients managed non-surgically, six had little or no pain; 12 had returned to work with six declaring little or no restrictions, and eight had returned to the same level of recreational activity as prior to injury with seven declaring little or no restrictions. Of 11 patients treated surgically, four had little or no pain; seven had returned to work with three declaring little or no restrictions, three had returned to the same level of recreational activity as prior to injury and four declared little or no restrictions. There was no correlation found between vertebral collapse, kyphosis, retropulsion and clinical outcome. Patients who had non-operative management reported a good functional outcome. However, patients who required surgical stabilisation due to different fracture characteristics reported a poorer functional outcome.

Activities of Daily Living↗
PubMed2004

The natural history of the periacetabular fragment following Ganz osteotomy.

The vascularity of the acetabular free fragment in Ganz osteotomies has remained a concern. This study aims to assess the role of MR imaging in the postoperative evaluation of Ganz osteotomies. Twenty patients (19 females, 1 male), average age 24 years (range, 12-36 years), had sequential magnetic resonance imaging studies of the pelvis at 6 weeks and 6 months following Ganz osteotomies. Normal healing with no evidence of periosteotomy edema was seen in 17 patients at 6 weeks. Three patients showed evidence of reduced vascularity. In two of these, there were focal changes suggestive of subclinical ischemia. The other had gross signal changes in the osteotomy fragment suggestive of diffuse ischemia. The patients with focal changes were asymptomatic and had normal 6-month scans. The patient with diffuse changes complained of persistent groin pain, which resolved after 4 months. The 6-month scan showed some persistent vascular changes. The scan at 1 year showed complete resolution. The study suggests that Ganz osteotomy has minimal effect on the vascularity of the acetabular free fragment.

Acetabulum↗
PubMed2003

Anterior displacement correlates with neurological impairment in cervical facet dislocations.

We studied all patients with either unifacetal or bifacetal dislocations treated in our National Spinal Injuries Unit between January 1996 and December 2000. There were 25 cases, of which 13 were unifacetal and 12 bifacetal. Craniocervical traction was employed in 21 cases and closed reduction achieved in 11. Eighteen patients underwent surgical stabilisation. Traction weights of up to 36 kg were employed, but there was no relationship found between the level of dislocation and traction weight. Anterior translation was measured by a newly described method, and we found a statistically significant correlation between the neurological score on admission and the degree of anterior translation.

Adolescent↗
PubMed2003

Percutaneous cementoplasty of acetabular bony metastasis.

The development of malignant lesions in the acetabulum can lead to painful and disabling bone destruction. Lytic metastases of the acetabulum are frequent, causing pathologic fractures, pain and disability. The literature is sparse in relation to the exact indications and technique for this procedure. Percutaneous injection of methylmethacrylate or ethanol may provide marked pain relief or bone strengthening in patients, with malignant acetabular destruction, who are unable to tolerate surgery. Injection of methylmethacrylate is usually indicated when the weight-bearing part of the acetabulum is involved. The goals of treatment are pain relief and mechanical strengthening of the acetabulum. Radiography and computed tomography must be performed prior to therapeutic percutaneous injection to assess the location and extent of the lytic process, the presence of cortical destruction or fracture, and the presence of soft-tissue involvement. We report a case of a 39-year-old woman with a secondary acetabular lesion, which was treated successfully with percutaneous acetabular cementoplasty. We describe a novel technique used to inject cement into the lesion, allowing for greater cement volume and pressurisation within the lesion.

Acetabulum↗
PubMed2002

Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy.

In part A of this study, patients were randomised to cohorts receiving darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy.

Adult↗
PubMed2001

A dose-finding and safety study of novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia in patients receiving multicycle chemotherapy.

Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg(-1)wk(-1)) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose-response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg(-1)wk(-1)cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl(-1)respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing.

Adult↗
PubMed1998

Dose escalation study of carboplatin and cyclophosphamide with filgrastim support: a phase I study.

This clinical trial was designed to explore dose escalation of carboplatin and cyclophosphamide when supported with filgrastim. Twenty-seven patients who had advanced solid tumors received up to six cycles of treatment; a total of 92 cycles of chemotherapy were delivered. Two control groups received standard-dose carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2), with and without filgrastim. Subsequently, the doses of both carboplatin and cyclophosphamide were increased simultaneously by 50% of the standard dose in sequential cohorts. Doses of up to 2.5 times the standard dose were explored. A final dose of carboplatin, 600 mg/m2, and cyclophosphamide, 1,500 mg/m2, was tested in 4 patients. The duration of neutropenia was brief, even at the highest dose levels. The mean duration of grade 3 or 4 neutropenia was 5.8 days at standard dose without filgrastim and 5.4 days at 2.5 times standard dose with filgrastim. More severe neutropenia was more prolonged at higher doses but remained brief in duration. The mean duration of neutropenia of less than 100 x 10(6)/l was 0.4 days at standard dose without filgrastim and 1.3 days at 2.5 times standard dose. There was no evidence of cumulative neutropenia over repeated cycles of treatment. In contrast, thrombocytopenia was both dose limiting and cumulative. The mean duration of grade 3 or 4 thrombocytopenia was 1.6 days at standard dose and 9.6 days at 2.5 times standard dose. An average of 2.3 platelet transfusions per cycle of treatment was required at the highest dose. Thrombocytopenia was worse with repetitive cycles of therapy. The mean duration of grade 3 or 4 thrombocytopenia was 2.2 days after the first cycle of chemotherapy and 7.8 days after cycle four. The maximum tolerated dose, as defined prospectively, was not reached but further dose escalation was not thought to be warranted because of the severity of thrombocytopenia. When supported with filgrastim, carboplatin and cyclophosphamide can be administered safely with substantially increased dose and acceptable toxicity.

Adolescent↗
PubMed1997

Randomized, blinded, placebo-controlled phase I trial of pegylated recombinant human megakaryocyte growth and development factor with filgrastim after dose-intensive chemotherapy in patients with advanced cancer.

Thrombocytopenia caused by chemotherapy is an important cause of morbidity and mortality in the treatment of malignant disease. Recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is a potent stimulator of megakaryocytopoiesis and prevents chemotherapy-induced thrombocytopenia in preclinical studies. We administered PEG-rHuMGDF with filgrastim after dose-intensive chemotherapy to 41 patients with advanced cancers to determine its safety and effects on hematologic recovery. Carboplatin 600 mg/m2 and cyclophosphamide 1,200 mg/m2 were administered to patients with advanced cancer. Patients were randomly assigned to receive blinded study drug, either PEG-rHuMGDF or placebo (3-to-1 ratio), commencing the day after chemotherapy. PEG-rHuMGDF was given at doses of 0.03, 0.1, 0.3, 1.0, 3.0, and 5.0 microg per kilogram body weight by daily subcutaneous injection for between 7 and 20 days. All patients received concurrent filgrastim 5 microg per kilogram body weight per day until neutrophil recovery. Fifteen patients had received PEG-rHuMGDF alone in a previous phase I study. Platelet function and peripheral blood progenitor cells (PBPC) were assessed. PEG-rHuMGDF enhanced platelet recovery in a dose-related manner when compared with placebo. The platelet nadir occurred earlier in patients given PEG-rHuMGDF (P = .002) but there was no difference in the depth of the nadir. Recovery to baseline platelet count was achieved significantly earlier following PEG-rHuMGDF administration compared with placebo (median, 17 days for PEG-rHuMGDF 0.3 to 5.0 microg/kg versus 22 days for placebo, P = .014). In addition, platelet recovery was faster in patients who had previously received PEG-rHuMGDF, suggesting that pretreatment might be beneficial. Platelet function did not change during or after administration of PEG-rHuMGDF. Levels of PBPC on day 15 after chemotherapy were significantly greater in patients administered PEG-rHuMGDF 0.3 to 5.0 microg/kg and filgrastim compared with those given placebo plus filgrastim. PEG-rHuMGDF was well tolerated at all doses. Two patients given PEG-rHuMGDF had a thrombotic episode. PEG-rHuMGDF accelerates platelet recovery after moderately dose-intensive carboplatin and cyclophosphamide, and is likely to be clinically useful in treatment of chemotherapy-induced thrombocytopenia. Because it enhances mobilization of PBPC by filgrastim, PEG-rHuMGDF might also allow more efficient collection of stem cells for autologous or allogeneic transplantation.

Adult↗
PubMed1997

Multilineage mobilization of peripheral blood progenitor cells in humans following administration of PEG-rHuMGDF.

The most important physiological regulator of megakaryocytopoiesis is the ligand for the c-mpl receptor (thrombopoietin/megakaryocyte growth and development factor, MGDF). We examined the effect of pegylated-recombinant human MGDF (PEG-rHuMGDF): patients received PEG-rHuMGDF at doses of 0.03, 0.1, 0.3 or 1.0 microg/kg/d or placebo for 10d maximum in a double-blinded randomized study. There was a dose-dependent elevation in circulating platelet counts but no alteration in erythrocyte or total leucocyte counts. The number of bone marrow megakaryocytes was increased approximately 2-fold. The frequency of bone marrow progenitor cells was not altered. In contrast, both to the bone marrow results and to published pre-clinical data, there was a dose-dependent mobilization into the blood of progenitor cells of multiple cell lineages. Increased levels of Meg-CFC (maximum increase 30-fold), day 7 and day 14 GM-CFC and BFU-E were demonstrated at doses of 0.3 and 1.0 microg/kg/d PEG-rHuMGDF. At 0.1 microg/kg/d, mobilization of Meg-CFC alone occurred in two-thirds of patients. Maximum blood levels of progenitor cells occurred at day 12. Thus, administration of PEG-rHuMGDF to humans resulted in mobilization of progenitor cells of multiple lineages despite its 'lineage-specific' activity on mature cell development.

Adult↗
PubMed1996

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation.

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.

Cohort Studies↗
PubMed1996

Tendon shift in hallux valgus: observations at MR imaging.

OBJECTIVE: This study was undertaken to demonstrate a shift in tendon alignment at the first metatarsophalangeal joint in patients with hallux valgus by means of magnetic resonance imaging. DESIGN: Ten normal feet and 20 feet with the hallux valgus deformity conforming to conventional clinical and radiographic criteria were prospectively studied using magnetic resonance imaging. Correlation was made between tendon position at the first metatarsophalangeal joint and the severity of the hallux valgus deformity. RESULTS: There is a significant shift in tendon position at the first metatarsophalangeal joint of patients with hallux valgus. The insertion of the abductor hallucis tendon is markedly plantarward and the flexor and extensor tendons bowstring at the first metatarsophalangeal joint compared with patients without the deformity. The severity of the tendon shift correlates with the hallux valgus angle and clinical severity of the hallux valgus deformity in each case. CONCLUSION: Patients with hallux valgus have a significant tendon shift at the first metatarsophalangeal joint which appears to contribute to development of the deformity.

Case-Control Studies↗
PubMed1994

Computed tomography of the retroperitoneum in patients with femoral neuropathy.

The authors illustrate the value of computed tomography (CT) of the retroperitoneum in patients presenting with femoral nerve signs. They describe 28 such patients, examined at a tertiary-care hospital between June 1990 and January 1993, in whom CT of the retroperitoneum contributed significantly to the diagnosis. The patients, 19 males and 9 females, ranged in age from 11 to 81 years. CT showed disease of the psoas compartment in 17 cases; the condition was due to a malignant lesion in 9 cases and was secondary to infection in 5 and to other causes in 3. Disease of the iliacus compartment was shown in 11 cases; it was due to a malignant lesion in 6 cases and was secondary to hemorrhage in 2, to infection in 1 and to a bursa in 1. The diagnostic features of the diseases encountered are discussed, and the importance of performing CT early is stressed.

Adolescent↗
PubMed1993

Radiographic features that enable assessment of first metatarsal rotation: the role of pronation in hallux valgus.

This study describes a method of detecting first metatarsal pronation on the basis of the movement of the inferior tuberosity of the base of 20 cadaveric first metatarsals at 0 degrees, 10 degrees, 20 degrees and 30 degrees pronation. On pronation, the inferior tuberosity of the base of the first metatarsal moved lateral to the mid-line axis. At 10 degrees, the tuberosity pointed to the junction of the inner third and outer two-thirds of a line between the midpoint and lateral tubercle of the base. At 20 degrees, it pointed to the junction of the inner two-thirds and outer third of that line. At 30 degrees, it pointed to the outer margin of the lateral third. Using these features, the amount of first metatarsal pronation in 100 consecutive weight-bearing views of feet was recorded and plotted against the corresponding intermetatarsal angles in those feet. Four of 43 patients with an intermetatarsal angle of less than 9 degrees had pronation greater than 10 degrees, 48 of 57 patients with an intermetatarsal angle greater than 9 degrees had pronation greater than 10 degrees (P < 0.001). As intermetatarsal angles increase, the amount of first metatarsal pronation increases (r = 0.69). Pronation and varus deviation of the first metatarsal are linked; both alter the tendon balance maintaining proximal phalanx alignment and lead to the development of hallux valgus.

Hallux Valgus↗