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Biomedical subjects

P Shuttleworth

Publications and source records attributed to P Shuttleworth.

10 recordsLinked to original sources
PubMed2006

Pamidronate reduces bone loss after allogeneic stem cell transplantation.

BACKGROUND: Rapid bone loss occurs from the proximal femur after allogeneic stem cell transplantation (alloSCT). OBJECTIVE: The objective of the study was to evaluate effects of high-dose pamidronate therapy on bone loss (BMD) after alloSCT. DESIGN: This was a randomized, multicenter, open-label, 12-month prospective study of iv pamidronate (90 mg/month) beginning before conditioning vs. no pamidronate. All 116 patients also received calcitriol (0.25 microg/d) and calcium (1000 mg/d), which were continued for another year. MAIN OUTCOME MEASURES: Primary objectives were to compare changes in BMD 12 months after alloSCT at the femoral neck, lumbar spine, and total hip between the treatment arms and assess influences of glucocorticoid and cyclosporin therapy on these changes. RESULTS: Pamidronate reduced bone loss at the spine, femoral neck, and total hip by 5.6, 7.7, and 4.9% (all P < or = 0.003), respectively, at 12 months. However, BMD of the femoral neck and total hip was still 2.8 and 3.5% lower than baseline, respectively (P < 0.05) with pamidronate. Only differences at the total hip remained significant between the two groups at 24 months. Benefits were restricted to patients receiving an average daily prednisolone dose greater than 10 mg and cyclosporin therapy for more than 5 months within the first 6 months of alloSCT. CONCLUSIONS: Pamidronate markedly reduced but did not completely prevent postallogeneic bone marrow transplantation bone loss. BMD benefits were greatest in patients on higher doses of immunosuppressive therapy, but most were lost 12 months after stopping pamidronate. Studies of more potent bisphosphonates or anabolic therapy with PTH after alloSCT are warranted with the aim of durable maintenance of bone mass.

Adolescent↗
PubMed2005

Autografting followed by rituximab for chemosensitive mantle cell lymphoma: a pilot study and literature review.

Mantle cell lymphoma (MCL) is rarely cured with either conventional-dose chemotherapy or autografting. Recent evidence suggests that anti-CD20 monoclonal antibody therapy (rituximab) in combination with chemotherapy may improve the response rate. We report a pilot study of autografting using busulfan-melphalan conditioning followed by rituximab in 9 patients (median age 52 years) with chemosensitive MCL. Rituximab was given for 4 doses of 375 mg/m(2) between 4 and 10 weeks post-transplant. Three of 5 patients autografted after induction therapy remain alive in clinical and molecular complete remission at 33-50 months post-transplant. Only 1 of 4 patients autografted after relapse remains in complete remission. Two of the 3 patients with persistent marrow molecular positivity post-autograft became negative after rituximab therapy. Molecular negativity was first observed in 2 patients only after rituximab therapy. Overall, 2 patients have relapsed and the remaining 3 died of late-onset respiratory failure, probably reflecting infection and/or aggressive conditioning in an older patient population. These preliminary results, together with a review of the literature, suggest that the combination of autografting and rituximab may lead to durable molecular remissions in patients with chemosensitive MCL. Further studies are required to clarify whether the administration of rituximab: (1) is optimal pre- or post-autograft and (2) impacts on the incidence of infection and idiopathic pneumonitis in this context.

Antibodies, Monoclonal↗
PubMed2002

A phase I dose-escalation study of etoposide continuous infusion added to busulphan/cyclophosphamide as conditioning prior to autologous or allogeneic stem cell transplantation.

Relapse of the primary disease remains the predominant cause of death following bone marrow transplantation for high-risk haematological malignancies. Improved supportive care and patient selection have resulted significant improvements in toxicity with standard conditioning regimens. Further dose intensification to reduce the risk of relapse may therefore be feasible. We determined the maximal tolerated dose (MTD) of a 5-day continuous infusion (CI) of etoposide when added to oral busulphan 16 mg/kg and intravenous cyclophosphamide 120 mg/kg (Bu/Cy) as conditioning in 44 autograft and 18 allograft recipients at high risk of relapse. The major toxicity of escalating doses of etoposide was oral and gastro-intestinal mucositis, reflected by a statistically significant increase in the requirement for total parenteral nutrition in both autografts and allograft recipients. Time to neutrophil and platelet recovery, opiate analgesia requirements, and duration of hospitalization were not affected by etoposide dose escalation. The MTD in autograft recipients was 300 mg/m(2)/day (1500 mg/m(2) total dose), and 100 mg/m(2)/day (500 mg/m(2) total dose) for allograft recipients. Mucositis and hepatotoxicity were more frequent in allograft recipients, suggesting that methotrexate may have contributed to the lower tolerable dose in these patients. As a consequence, further dose escalation may not be possible in heavily pre-treated patients undergoing allogeneic transplantation. Conversely, high dose CI etoposide can be added with relative safety to Bu/Cy in autograft recipients.

Adolescent↗
PubMed1994

A comparative study of several antibiotic formulations using a design based on a combination of balanced incomplete blocks and Latin squares.

A practical application of an experimental design, suitable for the comparison of several treatments, and based on combining balanced incomplete blocks and Latin squares balanced for carryover effects, is presented in the context of comparing a number of paediatric antibiotic formulations for taste, smell and colour. The recommended designs originally suggested by Patterson, have the advantage of balanced incomplete blocks, in that a single trial may be used to compare a larger number of treatments than may reasonably be given to any individual subject. In addition, the incorporation of suitably chosen Latin squares allows for assessment of any effect of order of presentation of the treatments and for any simple first-order carryover effect of one treatment into the following treatment period. Inclusion of such effects in the overall analysis could result in the reduction of bias in the comparisons of the treatments.

Analysis of Variance↗
PubMed1984

Fresh frozen plasma: a solution to heparin resistance during cardiopulmonary bypass.

The reasons for the highly variable response of patients to heparin remain incompletely understood. Empirical maintenance of the activated clotting time (ACT) at levels of 400 to 480 seconds appears to be safe for cardiopulmonary bypass (CPB). For patients with ACT responses lower than predicted for initial heparin doses, titration with additional heparin has been customary. In 44 patients undergoing cardiopulmonary bypass, 20 patients were identified as having initial ACTs of 300 seconds or less after receiving 300 units per kilogram of heparin. In 11 of them, ACTs were titrated to 400 to 480 seconds with additional heparin. Nine were given 2 units of fresh frozen plasma shortly after institution of CPB. In this group, there was significant augmentation of the ACT immediately after infusion of plasma. No differences in total heparin dosages given during CPB were found between 24 control patients with initially acceptable ACTs and the group receiving fresh frozen plasma. In contrast, more heparin was necessary in the patients with a low ACT titrated with heparin alone. Data also indicated that protamine sulfate requirements were substantially lower after administration of plasma than were those in either the control or the heparin-titrated, low ACT group. Fresh frozen plasma appears to "normalize" the heparin-ACT dose-response curve in heparin-resistant patients and to lessen total heparin requirements during CPB.

Adult↗
PubMedDate not supplied

Cladribine followed by autologous stem-cell transplantation in progressive multiple sclerosis.

We studied the safety of autologous peripheral blood stem-cell transplantation (PBSCT) in four patients with progressive multiple sclerosis. Clinical and magnetic resonance imaging outcomes were secondary end-points. Cladribine administration preceded filgrastim-primed PBSC collection, aiming for lymphocyte depletion. Conditioning was with antithymocyte globulin and cyclophosphamide. The procedure was well tolerated, but without obvious clinical benefit. The study was terminated when other therapeutic options with lower morbidity became available.

Adult↗