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Biomedical subjects

R A Sharp

Publications and source records attributed to R A Sharp.

At least 19 recordsLinked to original sources
PubMed1998

Autologous transplantation in chronic myeloid leukaemia using peripheral blood stem cells.

Forty-three patients with chronic myeloid leukaemia in first chronic phase were recruited to study intensive chemotherapy (idarubicin plus cytarabine; IdAC) followed by collection of peripheral blood stem cells (PBSC) in the recovery phase. PBSC autografting was performed on 32 patients. One patient died during mobilization and three died following autograft. All procedural deaths occurred in patients who received IdAc more than a year from diagnosis. Nine further patients died, eight following progression of CML. 72% of transplanted patients showed a major cytogenetic response but most cases have returned to Philadelphia-positive haemopoiesis. 62% of autografted patients remain alive (median survival from diagnosis 52 months). Four of the 11 patients who did not receive a transplant remain in chronic phase.

Adult↗
PubMed1998

Sequential malt lymphomas of the stomach, small intestine, and gall bladder.

Low grade lymphomas of mucosa associated lymphoid tissue (MALT) are indolent neoplasms that, although tending to remain localised for many years, may spread to other mucosal sites. A 53 year old woman treated by total gastrectomy for low grade MALT lymphoma of the stomach developed a recurrence in the small bowel 18 years later, and a further recurrence involving the gall bladder after three years in complete clinical remission after chemotherapy. In situ hybridisation showed that the small intestine and gall bladder recurrences had the same pattern of light chain restriction. Tumour from all three sites was shown to be derived from a single clone by the demonstration of an identical immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction. The case illustrates the propensity of MALT lymphomas to "home" to mucosal sites and gives an insight into their behavior over an extended follow up.

Female↗
PubMed1997

Treatment of chronic myeloid leukaemia in first chronic phase with idarubicin and cytarabine: mobilization of Philadelphia-negative peripheral blood stem cells.

Peripheral blood stem cell (PBSC) mobilization using idarubicin and cytarabine was investigated in 40 patients with chronic myeloid leukaemia in first chronic phase (CML CP1). Disease contamination was evaluated in harvests from 41/44 (93%) mobilization episodes. Using cytogenetics, 22/37 (59%) showed a complete or major response; Southern blot analysis demonstrated a complete or major response in 9/17 (53%). No harvests were RT-PCR negative. In the 41 evaluable episodes, more complete or major responses were seen when PBSC mobilization occurred within 24 months [17/23 (74%) versus 6/18 (33%); P = 0.02] and within 12 months of diagnosis [10/11 (91%) versus 13/30 (43%); P = 0.018]. 20 patients underwent PBSC transplantation and 18/20 successfully engrafted. Post-transplant cytogenetic analysis was available on 15 cases, of whom five achieved a major cytogenetic response at 1-3 months, with five partial cytogenetic remissions. Two of 40 patients died during mobilization therapy (5%) and three of 20 after the transplant (15%). Overall mortality was high at five of 40 patients, and the procedural mortality was 20%. This study demonstrates that Ph-negative PBSCs can be mobilized in a significant proportion of patients with CML CP1, with the best results observed within a year of diagnosis. These cells can subsequently be used for autologous transplantation, however, the impact on long-term survival requires longer follow-up, and potential benefits may be compromised by the high mortality.

Adult↗
PubMed1997

Peripheral blood progenitor cell mobilisation in patients with multiple myeloma following oral idarubicin and dexamethasone (Z-Dex) induction therapy.

Difficulties associated with current intensive induction regimens for multiple myeloma and uncertainty as to how to achieve optimal peripheral blood progenitor cell mobilisation (PBPC) prompted this study of an oral induction regimen, Z-Dex (oral idarubicin and dexamethasone) followed by PBPC mobilisation using four different regimens. Thirty-patients received Z-Dex (median age 56 years, range 46-66 years) including 24 patients with previously untreated disease. The overall response rate was 75% with a CR rate of 16.7% and PR rate of 75.7% in patients with previously untreated disease. We compared four mobilisation regimens: low-dose (LD) cyclophosphamide, high-dose (HD) cyclophosphamide, cis-platin/VP16 and cis-platin, Ara-C and dexamethasone (DHAP). Failure to mobilise optimal numbers of PBPCs (>1.0 x 10(6) CD34+ cells/kg and >20 x 10(4) CFU-GM/kg) was seen in two patients who received LD cyclophosphamide, in two patients who received HD cyclophosphamide and three patients who received cis-platin/VP16. No patient failed to mobilise adequate numbers of PBPCs following DHAP. In previously untreated patients, DHAP mobilised significantly more PBPC than LD cyclophosphamide (P=0.02), HD cyclophosphamide (P=0.0015) and cis-platin/VP16 (P=0.021). This study demonstrates the efficacy of Z-Dex in inducing tumour responses in patients with multiple myeloma without limiting PBPC mobilisation in subsequent dose-intensive schedules. Furthermore, we also demonstrate that DHAP is superior to cyclophosphamide (low- and high-dose) and cis-platin/VP16 in mobilising PBPCs and demonstrated a degree of tumour control.

Administration, Oral↗
PubMed1996

A phase I/II trial of Z-Dex (oral idarubicin and dexamethasone), an oral equivalent of VAD, as initial therapy at diagnosis or progression in multiple myeloma.

We designed an oral equivalent regime to mimic VAD and its hybrids, using idarubicin and dexamethasone (Z-Dex) given in four cycles to induce cytoreduction prior to dose intensification in multiple myeloma cases. 20 patients (de novo n = 15, replaced VAD n = 2, relapsed n = 2, and resistant n = 1), 13 males and seven females with a median age of 54 years (range 40-65 years) received Z-Dex therapy. The overall response rate was 70% (14/20), with one patient (5%) achieving complete remission (CR). The response rate for previously untreated patients was 80% (12/15), with a CR rate of 6.7% (1/15). Both patients who received Z-Dex in place of VAD continued to respond. Myelosuppression was seen in 14/20 patients (70%); 4/20 (20%) developing severe neutropenia with one death from neutropenic sepsis. Gastrointestinal toxicity and alopecia were infrequently reported. Satisfactory responses can be obtained using an oral regime equivalent to VAD with tolerable toxicity and morbidity.

Administration, Oral↗
PubMed1996

An evaluation of the fit of porcelain inlays.

The effect of die spacer usage and three different porcelain build up techniques on inlay fit were investigated by impression wash methods and image analysis of sectioned replicas. All inlays were produced on machined cavities. Data from the impression wash technique indicated a mean misfit value of just over 100 microns. Image analysis showed a smaller mean misfit of 40-60 microns. In general, the use of die spacer resulted in a poorer fit and there were no significant differences between methods of porcelain application detected by either method.

Analysis of Variance↗
PubMed1991

Multiple myeloma and chronic myelomonocytic leukaemia developing in a patient with autoimmune disease.

A 64-year-old lady with a personal and family history of autoimmune disease developed chronic myelomonocytic leukaemia and multiple myeloma simultaneously. Her sister died of acute myelomonocytic leukaemia, but showed no evidence of autoimmune disease. It is possible that chronic immunological stimulation, perhaps by an autoantigen, may predispose toward malignant transformation in both plasma cell and monocyte series. However, the present observations raise the alternative possibility of a primary disorder of monocytes that predisposes toward both autoimmune disease and a clonal disorder of plasma cells.

Autoimmune Diseases↗
PubMed1990

Anti-tuberculous drugs and sideroblastic anaemia.

Two cases of sideroblastic anaemia associated with antituberculous therapy are reported. The first, in whom there was a constitutional chromosomal abnormality and peripheral neuropathy, recovered on withdrawal of isoniazid and pyridoxine treatment. The other, who had been given a four-drug combination including isoniazid and pyrazinamide and recovered on the withdrawal of isoniazid alone, highlights the increasing likelihood of this complication in patients treated for tuberculosis, since this drug combination has regained popularity in recent years.

Adult↗
PubMed1989

The differential diagnosis of polycythaemia--a bone marrow study (the bone marrow in polycythaemia).

Bone marrow sections from posterior iliac crest aspiration and/or trephine specimens have been examined in 39 patients with true polycythaemia, along with a variety of other clinical and laboratory data. The emphasis has been on objective assessment of cellularity and megakaryocyte concentration in a prospective four year study. In patients with untreated primary polycythaemia mean cellularity was 87.0% and 86.4% for aspirate and trephine specimens compared with 55.5% and 48.7% for secondary cases and 48.3% and 45.5% for controls. Eighty per cent of primary polycythemia patients had moderate to marked megakaryocytic hyperplasia. We conclude that, in the presence of an elevated red cell volume, marrow cellularity of greater than 75%, particularly when accompanied by megakaryocytic hyperplasia, of iliac crest aspirate or trephine specimens is sufficient per se to establish a diagnosis of polycythaemia rubra vera.

Bone Marrow Cells↗
PubMed1987

t(3;5)(q21;q31) in a myelodysplastic syndrome.

Cytogenetic analysis from the bone marrow of a patient with a myelodysplastic syndrome revealed the balanced translocation t(3;5)(q21;q31). Although this translocation has recently been described in six cases of AML, this is the first such observation in a preleukaemic syndrome. Subsequent evolution into RAEB and AML(M2) was noted without the acquisition of additional cytogenetic changes and complete remission achieved with conventional cytotoxic chemotherapy. The relationships with other acquired abnormalities of chromosomes 3 and 5 in MDS/AML are discussed.

Adult↗
PubMed1987

Unresponsiveness to skin testing with bacterial antigens in patients with haemophilia A not apparently infected with human immunodeficiency virus (HIV).

Unresponsiveness to skin testing with PPD and tetanus toxoid was commonly seen in patients with haemophilia A but not infected with human immunodeficiency virus but was uncommon in controls. Vaccination history indicated that the unresponsive patients had not been immunised in childhood. Other tests of immune competence (skin tests with other antigens, lymphocyte stimulation with mitogens and antigens, and viral serology) showed that the haemophilia A patients had an adequate response to pathogens to which they had been exposed. Five of 12 such patients had a mild T4 lymphopenia, and this may have been related to parenteral administration of large quantities of protein.

Adolescent↗
PubMed1987

Polymyositis complicating staphylococcal septicaemia.

Inflammatory polymyositis can be precipitated by acute febrile illness of viral origin, but similar association with pyogenic bacterial illness is not recognised. We describe two cases in which recovery from staphylococcal septicaemia was complicated by a widespread inflammatory myopathy.

Female↗
PubMed1985

Purification and radioimmunoassays for superoxide dismutases in the mouse: tissue concentrations in different strains.

Both murine cuprozinc and manganosuperoxide dismutases were purified to electrophoretic homogeneity from liver; the former (dimer) had a sp. act. of 2600 U/mg and a subunit mol. wt. of 17,000, the latter (tetramer) 2300 U/mg and mol. wt. 23,000. Heterologous radioimmunoassays had sensitivities of 3.1 ng/ml for the former enzyme and 2.5 ng/ml for the latter, and were appicable across murine genetic lines (Balb/c, ob/ob, db/db). Islets had the lowest concentrations of both enzymes among the tissues studied, and this could explain their vulnerability to free-radical damage.

Animals↗