Biomedical subjects
A Manoharan
Publications and source records attributed to A Manoharan.
Identification of a 'genuine' mammalian homolog of nematodal CED-4: is the hunt over or do we need better guns?
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Use of whole blood platelet lumi-aggregometry to optimize anti-platelet therapy in patients with chronic myeloproliferative disorders.
Twenty-seven patients with chronic myeloproliferative disorders and in vitro evidence of platelet hyperactivity on whole blood platelet lumi-aggregometry were commenced on anti-platelet therapy comprising aspirin, clopidogrel, and/or odorless garlic and the studies were repeated to assess the efficacy of the therapeutic agent(s). Only 8 patients showed clear evidence of anti-platelet effect while receiving the standard low-dose (100 mg/day) aspirin therapy. Thirteen patients required a higher dosage of aspirin and/or an additional anti-platelet agent to achieve therapeutic adequacy. Lumi-aggregometry also proved useful to optimize therapy in the 6 patients who received clopidogrel or odorless garlic because of aspirin intolerance.
The expansion of megakaryocyte progenitors from CD34+-enriched mobilized peripheral blood stem cells is inhibited by Flt3-L.
This study aimed to determine the optimal growth factor combination for expansion of megakaryocyte (Mk) progenitors with clonogenic potential from CD34+-enriched mobilized peripheral blood stem cells (PBSC). Mobilized PBSC were monocyte depleted and CD34+ enriched, then cultured with various combinations of interleukin-3 (IL-3), IL-6, IL-11, Flt3 ligand (Flt3-L), stem cell factor (SCF), granulocyte-macrophage colonystimulating factor (GM-CSF), and erythropoietin (EPO), using a 2(7-3) IV fractional factorial design. Expansion of Mk committed progenitors (CD41+) and primitive precursors (CD61+ CD34+) was determined using FACS and colony-forming assays. Amplification of Mk progenitor production was attributed to IL-3 (p < 0.002), SCF (p < 0.001), and GM-CSF (p < 0.05). Flt3-L inhibited the production of total CD61+ cells (p < 0.05), CD61+CD34+ cells (p < 0.03), and total CD41a+ cells (p < 0.01). Addition of Flt3-L to the optimum growth factor combination of megakaryocyte growth and development factor (MGDF), SCF, IL-3, and GM-CSF caused the greatest increase in total nucleated cells but reduced Mk progenitor expansion. There was also a 20% reduction in Mk+ colonies from cells expanded in the presence of Flt3-L. Factorial analysis identified the optimal combination of growth factors required to expand Mk precursors with clonogenic potential. The addition of Flt3-L to the optimal combination of MGDF, SCF, IL-3, and GM-CSF reduced both the fold expansion of Mk progenitors and Mk colony numbers.
Progressive hepatic lymphoma successfully treated with regional chemotherapy through a hepatic artery catheter.
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Plasmapheresis as a potential treatment option for amiodarone-induced thyrotoxicosis.
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Development and characterization of a novel immobilized microbial membrane for rapid determination of biochemical oxygen demand load in industrial waste-waters.
The rapid determination of waste-water quality of waste-water treatment plants in terms of pollutional strength, i.e. biochemical oxygen demand (BOD) is difficult or even impossible using the chemical determination method. The present study reports the determination of BOD within minutes using microbial BOD sensors, as compared to the 5-day determination using the conventional method. Multiple criteria establish the basis for the development of a BOD biosensor useful for rapid and reliable BOD estimation in industrial waste-waters. Of these, preparation of a suitable novel immobilized microbial membrane used in conjunction with an apt transducer is discussed. As a result, a microbial biosensor based on a formulated, synergistic, pre-tested microbial consortium has been developed for the measurement of BOD load of various industrial waste-waters. The sensor showed maximum response in terms of current difference, when a cell concentration of 2.25 x 10(10) CFU, harvested in their log phase of growth were utilized for microbial membrane construction. The sensor showed a stability of 180 days when the prepared membranes were stored at a temperature of 4 degrees C in 50 mM phosphate buffer of pH 6.8. The reusability of the immobilized membranes was up to 200 cycles without appreciable loss of their response characteristics. A linear relationship between the current change and a glucose-glutamic acid (GAA) concentration up to 60 mg l(-1) was observed (r=0.999). The lower detection limit was 1.0 mg l(-1) BOD. The sensor response was reproducible within +/-5% of the mean in a series of ten samples having 44 mg l(-1) BOD using standard a GGA solution. When used for the BOD estimation of industrial waste-waters, a relatively good agreement was found between the two methods, i.e. 5-day BOD and that measured by the developed microbial sensor.
Platelet dysfunction in myelodysplastic syndromes: a clinicopathological study.
Forty-eight patients with myelodysplastic syndromes and a platelet count greater than 80 x 10(9)/L were the subjects of a study of platelet function. A whole-blood platelet lumi-aggregometer was used for simultaneous measurement of platelet aggregation by the impedance method and of adenosine triphosphate-dense granule release. The results were correlated with skin bleeding time and episodes of clinical bleeding or thrombosis. Thirty-five patients had at least 1 abnormal result indicating platelet hypoactivity; 7 patients had mixed platelet hypoactivity and hyperactivity; and 4 patients had platelet hyperactivity. Only 2 patients had normal results. There was good correlation between platelet hypoactivity and prolonged skin bleeding time (P = .005); however, several patients with platelet hypoactivity had normal skin bleeding times. This finding suggested that whole-blood platelet aggregation studies may be more sensitive than bleeding time in identification of patients at risk of bleeding. Clinical hemorrhage was frequent (32 patients) in this cohort despite platelet counts greater than 100 x 10(9)/L. This finding indicated platelet hypofunction was clinically important. In contrast, only 2 of the 13 patients with thrombotic events had evidence of platelet hyperactivity, suggesting that other clinical factors are probably more important determinants of thrombosis. These observations confirm that platelet dysfunction is common in patients with myelodysplastic syndromes and suggest a useful role for routine whole-blood platelet aggregation studies to identify patients at risk of bleeding.
Syndrome of myelofibrosis and osteosclerosis: a series of case reports and review of the literature.
Myelofibrosis (MF) is a chronic disorder characterized by bone marrow evidence of myeloid metaplasia associated with reactive fibrosis, angiogenesis, and osteosclerosis. We report serum biochemistry, noninvasive markers of bone turnover, tetracycline-labeled bone histomorphometry, and bone densitometry (DXA) data of four men presenting with newly diagnosed biopsy-proven MF and osteosclerosis. The mechanisms and putative growth factors responsible for this syndrome are examined.
Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia.
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Long-term remissions with weekly chlorambucil therapy in patients with intermediate-risk chronic lymphocytic leukaemia.
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Effect of pregnancy on isolated platelet factor 3 (PF3) defect.
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Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance.
AIMS: To determine whether various markers of bone turnover and/or plasma cytokines differ in patients with multiple myeloma (MM) compared with patients with monoclonal gammopathies of undetermined significance (MGUS). METHODS: We studied 22 MM patients and 18 MGUS patients presenting over an 18-month period and compared their data with those from 20 age- and sex-matched patients presenting with primary osteoporosis. According to the Salmon and Durie classification, there were eight patients with stage I, nine with stage II and five with stage III disease. All patients had densitometric evidence of osteoporosis and were classified according to bone marrow evidence of plasma cell dyscrasia. Measured variables included markers of bone formation and bone resorption, and plasma cytokines. RESULTS: Patients with MM and MGUS did not differ with respect to their mean age, male : female sex ratio, height, weight, serum calcium, 25-hydroxyvitamin D and parathyroid hormone concentrations. Patients with MM had significantly lower concentrations of haemoglobin (109 vs 135 g/L) and serum transforming growth factor (TGF)-beta (261 vs 348 pg/mL) than patients with MGUS, and higher concentrations of serum paraproteins (31.1 vs 7.4 g/L), beta2-microglobulin (3.5 vs 2.2 g/L), % plasma cell numbers (35.3 vs 2.1%) and urinary deoxypyridinoline excretion rates (u-DPYD; 7.7 vs 5.9 nmol/mmol creatinine; P < 0.05 for all comparisons). In multivariate analysis, the serum paraprotein (beta coefficient = -0.067; 95% confidence intervals (CI), -0.019 to -0.005; P = 0.0012), u-DPYD excretion rates (beta coefficient = -0.012; 95% CI, -0.113 to -0.02; P= 0.0058) and serum TGF-beta concentrations (beta coefficient = -0.002; 95% CI, -0.0002 to -0.02; P= 0.02) were the most important variables differentiating between MM and MGUS, after excluding lytic bone lesions, % plasma cell numbers and haemoglobin concentrations. CONCLUSIONS: The well-established criteria for diagnosing MM include the presence of lytic bone lesions, plasmacytosis, haemoglobin and paraprotein concentrations. The u-DPYD excretion rate, a sensitive non-invasive marker of bone resorption, may help in differentiating between MM and MGUS, as well as serving as a marker of underlying bone disease activity in these patients.
Population screening for HFE-associated haemochromatosis.
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Rapid assay for detection of chloramphenicol acetyl transferase in Haemophilus influenzae.
BACKGROUND & OBJECTIVES: Haemophilus influenzae causes a variety of life threatening infections in humans. Early detection of antimicrobial resistance is of importance in the treatment and management of infection. The modified Slack's method, a simple assay, has been evaluated in this study for the early detection of chloramphenicol resistance. METHODS: Fifty isolates of H. influenzae from invasive and non-invasive sites were included. Antimicrobial susceptibility testing was done by disc diffusion method and minimum inhibitory concentration (MIC) determination was performed for chloramphenicol only. Modified Slack's method was used to test for the production of chloramphenicol acetyl transferase (CAT). RESULTS: Invasive isolates showed higher degree of resistance to chloramphenicol (72%) compared to non-invasive ones (28%). One hundred per cent association was found between results of disc diffusion, MIC and CAT production amongst strains resistant to chloramphenicol. INTERPRETATION & CONCLUSION: The findings suggested that chloramphenicol still remains the drug of choice for treatment for non-invasive infection caused by H. influenzae. Modified Slack's method is a simple, rapid, inexpensive and reliable method for the detection of chloramphenicol resistance amongst H. influenzae.
Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.
AIM: To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis. METHODS: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital. RESULTS: With danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6-71.4; p = 0.02). Clinical recovery with danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2-16.7; p = 0.03). Overall clinical effectiveness of danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment. CONCLUSION: danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.
Gentle yet effective treatment for elderly patients with refractory or relapsing multiple myeloma.
Fourteen patients, aged 65-85 years, with refractory (11) or relapsing (3) multiple myeloma were treated with a "protracted-sequential" protocol comprising vincristine 1-2 mg or vindesine 3 mg/M(2) (max. 5 mg) IVI over 4 hr on D1, prednisolone 40-50 mg PO D1-14, and melphalan 2-4 mg PO or cyclophosphamide 50-100 mg PO D15-28; cycles were repeated at 4-6 weekly intervals. Treatment was continued for 12 months if the response was optimal or indefinitely if the response was suboptimal. Five patients responded optimally; their survival from the commencement of this protocol ranged from 30 to 120 months. The other nine patients achieved a partial response, their survival ranging from 4+ to 79 months. The treatment is simple, nontoxic, and as convenient as the "classic combination" of melphalan and prednisolone.