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Biomedical subjects

I Bunce

Publications and source records attributed to I Bunce.

12 recordsLinked to original sources
PubMed1999

Safe mobilization of normal progenitors in advanced chronic myeloid leukemia with intensive chemotherapy and granulocyte-colony stimulating factor.

Twenty-one patients with advanced chronic myeloid leukemia (late chronic phase (n = 8), accelerated phase (n = 11) and blast crisis (n = 2)) were treated with idarubicin, cytarabine, and etoposide followed by G-CSF and subsequent collection of peripheral blood progenitor cells in the early recovery phase. Treatment was reasonably well tolerated with no deaths or intensive care admissions. Despite the advanced phase of disease and heavy pretreatment with cytotoxics and interferon-alfa, 11 of 21 patients (52%) achieved a cytogenetic response. Of the nine major cytogenetic responses (complete (n = 3) and partial (n = 6)), seven achieved adequate progenitor collections for consideration for autologous transplantation. The only predictor of response was disease duration (P = 0.02). With a median follow-up of 1171 days from treatment it appears unlikely that G-CSF contributed to disease progression. Survival post-IcE was predicted by disease stage (P = 0.0001). Intensive chemotherapy followed by G-CSF allowed adequate yields of predominantly Philadelphia chromosome negative progenitor cells to be obtained from one-third of patients with advanced CML.

Adult↗
PubMed1999

Efficacy, safety and tolerability of anagrelide in the treatment of essential thrombocythaemia.

BACKGROUND: Essential thrombocythaemia (ET) has an associated risk of thrombotic and haemorrhagic complications, which can be minimised by control of the platelet count. Anagrelide selectively lowers the platelet count, however, there is little Australasian experience with its use and scant data on symptom control. AIMS: To evaluate the efficacy of anagrelide for platelet reduction and symptom control in a broad cohort of patients with well-defined ET, and to determine the safety and tolerability in such a population. METHODS: Seventeen patients with ET and a platelet count > 600 x 10(9)/L were prospectively enrolled. The evaluable four males and 12 females with a median age of 58 years (range 14-79) included ten patients (63%) previously treated with two or more agents and 12 patients (75%) who had failed other therapies. The median follow-up was seven months (range 15 days to 36 months). RESULTS: Anagrelide, in an average dose of 1.9 mg/day, reduced the platelet count from a mean of 728 x 10(9)/L (95% CI 611-845 x 10(9)/L) to 412 x 10(9)/L (95% CI 319-504 x 10(9)/L) (p < 0.001) and maintained it at this level. Fourteen patients (88%) had a platelet reduction to < 600 x 10(9)/L. All symptomatic patients had improvement in symptoms attributable to thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in a total of three patients (19%), including one death from an intracerebral haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a median of 151 days. Side effects included palpitations, abdominal pain and cough. CONCLUSIONS: Anagrelide is efficacious and safe in ET, both for platelet and symptom control. Minor side effects are common, however, tend to occur early and resolve spontaneously in most cases.

Adolescent↗
PubMed1999

Long-term interferon-alpha 2A does not induce sustained hematologic remission in younger patients with essential thrombocythemia.

The ability of Interferon alpha (alpha-IFN) to alter the natural history of essential thrombocythemia (ET) and induce sustained hematologic remission would provide further impetus to consider this agent in younger patients with this disease and may influence the decision to commence treatment in asymptomatic patients. This study has failed to demonstrate any sustained hematologic remissions after cessation of long-term (2 years) alpha-IFN administration in a group of 34 female patients with a median age of 41 years (range 14-68) who were considered at intermediate to high risk of thrombotic complications. In the twenty-one patients completing two years of therapy, 13 (62%) had complete hematological responses (CHR; platelet count <400 x 10(9)/L), 7 (33%) partial hematological responses (PHR; platelet count 400-600 x 10(9)/L) and no thrombotic or hemorrhagic complications occurred. In all patients who discontinued alpha-IFN at 2 years, platelet counts rose above the normal range within 1-4 months and the majority required reinstitution of some form of therapy. The inability of long-term alpha-IFN to induce sustained, unmaintained hematologic remission argues strongly against any significant effect on the neoplastic clone at the doses used in this study. This study does, however, confirm the efficacy of long-term alpha-IFN in younger female patients with ET, a group not previously well represented in clinical trials of the agent.

Adolescent↗
PubMed1998

In vivo assessment of neovascularization of liver metastases using perfusion CT.

Neovascularization of tumours produces a high microvessel density. Although diagnostic imaging is unable to visualize microvessels directly, it is possible to demonstrate associated changes in tissue perfusion. The aim of this study was to use the quantitative functional information and high spatial resolution of perfusion computed tomography to study neovascularization of hepatic metastases. Perfusion CT was performed in 13 patients with hepatic metastases from various primary tumours. Arterial perfusion was measured in the metastasis; both arterial and portal perfusion were measured in a small rim of liver tissue immediately adjacent to the metastasis. Perfusion measurements were correlated against survival of the patient in nine cases. Arterial perfusion was increased above normal values, both in the metastasis (median: 0.62 ml min-1 ml-1; range: 0.26-3.05 ml min-1 ml-1) and in the adjacent liver (median: 0.51 ml min-1 ml-1; range: 0.14-1.60 ml min-1 ml-1). Portal perfusion of adjacent liver was highly variable (median: 0.30 ml min-1 ml-1; range: 0.05-1.85 ml min-1 ml-1). Arterial perfusion was positively correlated with portal perfusion within liver tissue adjacent to metastases (p < 0.05, r = 0.58), a reversal of the normal situation. Survival of the patient correlated with arterial perfusion within the metastasis (p < 0.05, r = 0.69) but more closely with arterial perfusion in the adjacent liver (p < 0.02, r = 0.78). In conclusion, alterations in perfusion within metastases and adjacent liver are in accordance with the histological features of neovascularization. Perfusion CT offers a method for studying neovascularization in the living patient and offers prognostic information.

Carcinoma↗
PubMed1996

High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.

Adult↗
PubMed1992

All-trans retinoic acid in the treatment of acute promyelocytic leukaemia.

All-trans-retinoic acid (ATRA) is known to induce differentiation of promyelocytes in vitro and also to induce remission of acute promyelocytic leukaemia in vivo. We treated 11 patients with poor prognosis acute promyelocytic leukaemia (APL) with ATRA and obtained seven complete and one partial remission. Remissions took one to three months to achieve and were associated with adverse effects including dry skin and bone pain. In eight patients the white cell count rose above 20 x 10(9)/L within the first ten days of retinoic acid treatment and this was associated with the development of pulmonary leukostasis in three patients which was fatal in one. Another two patients died of intracranial haemorrhage also within the first ten days. ATRA is a promising new agent in the induction therapy of this particular category of acute leukaemia.

Adult↗
PubMed1986

Platelet function in patients receiving enprostil.

The effect of 14 days of treatment with enprostil (35 micrograms twice daily) or ranitidine (150 mg twice daily) on platelet function in 21 patients with duodenal ulcer was evaluated in a double-bind, randomized, parallel study. Platelet function, as determined by the results of a coagulation screen, aggregation tests, and an assay for plasma beta-thromboglobulin levels, was assessed before and after 14 days of treatment. No effect on platelet function was observed with either drug in this group of patients.

Adult↗
PubMed1983

An immunoassay for human D dimer using monoclonal antibodies.

Monoclonal antibodies (MAb) were raised against human D dimer. The hybridomas were screened with a solid phase enzyme immunoassay against D dimer and fibrinogen degradation products. Among the panel of MAb identified, two distinct patterns emerged; the majority belonging to a panspecific class reacting against epitopes present on both D dimer and fibrinogen degradation product Dcate and a monospecific class reacting with determinants apparently present only on D dimer. A number of MAb were further characterised for their ability to specifically capture antigen in a solid phase enzyme immunoassay and assays were developed which have a sensitivity of 10 ng/ml for D dimer or crosslinked fibrin derivatives and may be suitable for detection of crosslinked derivatives in serum and plasma samples in a clinical situation.

Animals↗
PubMed1973

Interaction of angiotensin with disseminated intravascular coagulation: a possible mechanism in the genesis of acute renal failure.

Because of the importance of the renin-angiotensin system in renal homeostatic mechanisms, the effect of angiotensin administration upon disseminated intravascular coagulation has been studied in rabbits. An infusion of angiotensin II (0.1 mug/kg/min for 2 hours) produced neither histologic abnormalities in the kidneys nor an elevation of creatinine. After an infusion of thrombin (2.0 units/kg/min for 2 hours) only 3 of 10 rabbits, when sacrified 24 hours later, showed histologic lesions comprised of occasional fibrin thrombi and foci of tubular necrosis. Creatinine levels did not rise. In contrast, the combination of angiotensin and thrombin resulted in renal lesions in 12 of 14 animals. Four had frank cortical necrosis, while combinations of tubular necrosis, glomerular thrombosis and segmental glomerular infarction occurred in the others, together with elevated creatinine levels. Blockade of alpha-adrenoreceptors with phenoxybenzamine in 12 animals did not prevent either these histologic changes or creatinine elevation, showing that the effect of angiotensin was independent of alpha-adrenoreceptor stimulation. The synergistic interaction between angiotensin and disseminated intravascular coagulation was not explained by differences in the consumption of plasma fibrinogen but apparently was due to localization of fibrin thrombi within glomerular capillaries by the vasomotor actions of angiotensin, as has previously been shown to occur with alpha-adrenoreceptor simulation. Such a mechanism might contribute to renal glomerular deposition of fibrin in acute ischemic renal failure.

Acute Kidney Injury↗
PubMedDate not supplied

CT measurement of perfusion and permeability within lymphoma masses and its ability to assess grade, activity, and chemotherapeutic response.

PURPOSE: Structural CT criteria such as nodal size and appearance have a poor correlation with the grade and activity of a lymphoma mass. This study investigates the potential for functional CT perfusion and permeability measurements to assess lymphoma grade and activity. METHOD: Thirty-nine patients with proven lymphoma underwent 47 dynamic contrast-enhanced CT studies. Lymphoma grade was classified as low or intermediate/high. In seven patients who underwent repeated studies, measurements were correlated against change in disease activity in the intervening period. RESULTS: Median perfusion values were higher in active disease (0.55 vs. 0.37 ml/min/ml) and intermediate/high-grade lymphoma (0.56 vs. 0.46 ml/min/ml). Perfusion below 0.2 ml/min/ml implied inactive disease (p < 0.03), whereas > 0.5 ml/min/ml suggested intermediate/high-grade lymphoma (p = 0.11). Median values of permeability were little different between patient groups. Only perfusion fell when disease became inactive. CONCLUSION: Only CT perfusion measurements of nodes have potential for assessing lymphoma grade, activity, and treatment response.

Capillary Permeability↗