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D Gottlieb

Publications and source records attributed to D Gottlieb.

At least 19 recordsLinked to original sources
PubMed2007

Allogeneic bone marrow transplant for refractory mediastinal germ cell tumour: possible evidence of graft-versus-tumour effect.

Mediastinal germ cell tumours (GCT) carry a poor prognosis, particularly after relapse. We have reviewed the published reports of current treatments and describe a case with a cure after an allogeneic bone marrow transplant, which is not reported in the current published data. We believe that GCT may be susceptible to a graft-versus-tumour effect and suggest that patients with relapsed GCT be considered for allogeneic transplantation.

Adult↗
PubMed2006

Reduced-intensity allogeneic haemopoietic stem cell transplantation induces durable responses in patients with chronic B-lymphoproliferative disorders.

Thirty-six patients with chronic B-lymphoproliferative disorders (B-LPD) underwent reduced-intensity allogeneic transplantation (RIT) from HLA-identical related donors. Diagnoses included follicular (n=17), mantle cell (n=9) and small lymphocytic lymphoma (n=2), and chronic lymphocytic leukaemia (n=8). Median age at transplant was 51 years (range, 30-66) and time from diagnosis was 3.4 years (range, 0.3-9.5). At transplant, 28% were in CR, 36% were in PR and 36% were chemorefractory. Conditioning therapy included fludarabine and either cyclophosphamide (n=27) or melphalan (n=9). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin (CsA)/methotrexate (n=21), CsA/mycophenolate mofetil (n=13) or CsA alone (n=2). Eight patients died owing to acute GVHD (n=3), infection in association with chronic GVHD (n=4) and intra-abdominal bleeding (n=1). Treatment-related mortality was 8% at day 100, and 17 and 20% at one and two years, respectively. The cumulative incidence of grade II-IV acute GVHD was 58%, whereas limited and extensive chronic GVHD occurred in 25 and 56%, respectively. No patient has relapsed or progressed. At a median follow-up of 48 months, overall survival probability is 80% (95% CI, 67-93%). We confirm that RIT in chronic B-LPD can result in high and durable CR rates but with significant incidences of acute and chronic GVHD.

Adolescent↗
PubMed2006

Fresh PBSC harvests, but not BM, show temperature-related loss of CD34 viability during storage and transport.

BACKGROUND: The optimum conditions for storage and transport of freshly harvested HPC in the liquid state are uncertain. It is not specified in commonly applied standards for stem cell transplantation. We used a viable CD34 assay to determine the optimum temperature for maintaining progenitor cell viability in freshly harvested BM and PBSC. Our aim was to identify standardized conditions for storage and transport of marrow or peripheral blood products that would optimize CD34 recovery, leading to better transplant outcomes. METHODS: Samples were aseptically removed from 46 fresh HPC harvests (34 PBSC and 12 BM) and stored at refrigerated temperature (2-8 degrees C), room temperature (18-24 degrees C) and 37 degrees C for up to 72 h. Samples were analyzed for viable CD34+ cells/microL at 0, 24, 48 and 72 h. RESULTS: The mean viable CD34+ yield prior to storage was 7.7 x 10(6)/kg (range 0.7-30.3). The mean loss of viable CD34+ cells in HPC products at refrigerated temperature was 9.4%, 19.4% and 28% at 24, 48 and 72 h, respectively. In contrast, the mean loss of viable CD34+ cells at room temperature was 21.9%, 30.7% and 43.3% at 24, 48 and 72 h, respectively. No viable CD34+ cells remained after storage at 37 degrees C for 24 h. Only PBSC products and not BM showed temperature-related loss of CD34 viability. Greater loss of viable CD34+ cells was observed for allogeneic PBSC compared with autologous PBSC. DISCUSSION: These results demonstrate that the optimum temperature for maintaining the viability of CD34+ cells, during overnight storage and transport of freshly harvested HPC, is 2-8 degrees C. These findings will allow the development of standard guidelines for HPC storage and transport.

Adult↗
PubMed2006

Outpatient fractionated ifosfamide, carboplatin and etoposide as salvage therapy in relapsed and refractory non-Hodgkin's and Hodgkin's lymphoma.

We have treated 75 transplant-eligible patients with relapsed or refractory lymphoma using an outpatient-based fractionated regimen of ifosfamide, carboplatin and etoposide (ICE) for both salvage and stem cell mobilisation. Patients included DLBC (n = 33), follicular (n = 23), NK/T-cell (n = 3), mantle cell (n = 3) and Hodgkin's lymphoma (n = 13). Cycles of outpatient ICE were given every 21 days and consisted of: ifosfamide 5000 mg/m(2) i.v. fractionated into three equally divided doses and infused over 2-3 h on days 1-3, carboplatin (mg dose = 5 x AUC) i.v. over 1 h on day 1; and etoposide 100 mg/m(2) i.v. daily on days 1-3, plus filgrastim 5 microg/kg/day. Most patients with indolent lymphoma also received rituximab. The median age of patients was 52 years (range 26-69 years). Patients received a mean of 2.8 cycles of ICE. Non-haematological toxicities included grade 1/2 CNS toxicity in four patients, cardiac toxicity in two, reversible renal impairment and haematuria in one each. Haematological toxicity included grades III/IV thrombocytopenia and neutropenia with at least one cycle of ICE in 71% and 72% of patients, respectively. The median time to PBSC harvest was 14 days (range 10-20 days), while the median CD34(+) cell yield was 4.8 x 10(6)/kg (range 2.3-37.8). Five patients (7%) failed to mobilise PBSCs. The overall response rate to ICE was 89%, comprising 29% who achieved a CR and 60% who achieved a PR; for DLBCL, the overall response rate was 85% including 36% who achieved a CR and 49% who exhibited a PR. At a median follow-up of 24 months, the Kaplan-Meier estimates of the overall and event-free survival for all patients were 65% and 42%, respectively. For patients with DLBCL overall and event-free survival figures were 51% and 35%, respectively, at a median follow-up of 14 months. These data confirm the efficacy and tolerability of outpatient fractionated ICE as both a salvage and mobilisation regimen in relapsed/refractory lymphoma.

Adolescent↗
PubMed2003

Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease.

We have treated 38 transplant-eligible patients with relapsed/refractory non-Hodgkin's lymphoma and Hodgkin's disease using an outpatient-based regimen of ifosfamide, carboplatin and etoposide (ICE) for both salvage and peripheral blood stem cell mobilisation. Patients included relapsed or refractory diffuse large B-cell lymphoma (n = 17), follicular lymphoma (n = II), T-cell lymphoma (n = 2), mantle cell lymphoma (n = 2) and Hodgkin's disease (n = 6). Seven patients with diffuse large B-cell lymphoma and three patients with follicular lymphoma (26%) were considered chemorefractory. Cycles of ICE therapy were administered every 21 days as an outpatient and consisted of ifosfamide 5000 mg/m2 intravenously (i.v.) fractionated into three equally divided doses over 3 days, carboplatin [mg dose = 5 x area under the curve (AUC)] i.v. on day 1 and etoposide 100 mg/m2- i.v. daily for 3 days. Subsequently. granulocyte colony-stimulating factor (G-CSF)5 microg/kg subcutaneously (s.c.) was administered daily from day +5. Of the I I follicular lymphoma patients, 10 also received rituximab with ICE therapy. Median age of patients was 52 years (range 30-65). Patients received a mean of 2.6 cycles (range 1-4) of ICE. There were no toxic deaths and no significant non-haematological toxicities secondary to ICE therapy. Grade IV thrombocytopenia and grade IV neutropenia with at least one cycle of ICE were seen in 47% and 53% of patients, respectively. Median time to peripheral blood stem cell (PBSC) harvest was 14 days (range 10-20). while the median CD34+ cell yield was 5.2 x 10(6) cells/kg(range 2.3 x 10(6)-27.2 x 10(6)). Only one of the ICE-responders failed to mobilise PBSCs. The overall response rate to ICE was 87%. comprising 14 patients (37%) who achieved a complete response (CR) and 19 (50%) who achieved a partial response (PR). A total of 30 patients have undergone autologous stem cell transplantation(SCT) while two follicular lymphoma patients have received a non-myeloablative allogeneic SCT. Follow-up is short: however, the Kaplan-Meier estimate of the proportion of patients alive and event-free at a median follow-up of 11 months is 80% and 59%, respectively. Event-free survival for patients who achieved a CR after ICE and transplantation is 88% versus 45% for those who achieved a PR. These data confirm the efficacy and tolerability of fractionated ICE chemotherapy as both a salvage and mobilisation regimen that can be readily delivered in an outpatient setting.

Adult↗
PubMed2001

The influence of social support and perceived control on handicap and quality of life after stroke.

It has been suggested that external factors, such as perceived control of life and social support, influence the interactions of impairment, disability and handicap in the WHO model. Therefore, we assessed the effect of these two factors on the relationships between disability, handicap and quality of life in patients recovering from stroke. One hundred individuals, retrospectively and randomly selected from participants in an inpatient stroke rehabilitation program, were tested one year after discharge, using the Functional Independence Measure, the London Handicap Scale, the Life Satisfaction Assessment, the Tel-Aviv Social Support Instrument, and the Perceived Stress Scale. Impairment, disability, handicap and quality of life after stroke correlated positively and significantly with each other. Significant moderation of the influence that disability exerts on handicap was affected by perception of control, and by the influence of handicap over quality of life by social support. Thus, external factors can cause inconsistent interactions between components of the WHO model. Patient outcome may be improved if such factors are considered.

Aged↗
PubMed2001

Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia.

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.

Acute Disease↗
PubMed2001

A telephone-linked computer system for COPD care.

The current revolution in communications technology provides an opportunity for novel approaches to management of medical illness. As economic imperatives lead to a progressive reduction in the time that health-care providers spend with their patients, computerized, telephone-linked communication systems offer an inexpensive, widely available alternative with which patients and providers can maintain contact. Such systems may be particularly useful for providing ongoing monitoring and education of patients with chronic illnesses such as COPD. In this article, we describe the general application of telephone-linked communication systems in the health-care setting. We then present in detail one such system, which provides telephone-linked care for COPD (TLC-COPD). The operation of the system is described, as are its theoretical underpinnings in social learning theory. A randomized clinical trial currently is being performed to study the effects of the TLC-COPD system. The rationale for expected improvements in disease control and quality of life, and for a reduction in acute health-care utilization, is discussed.

Algorithms↗
PubMed2000

Ascorbic acid in idiopathic recurrent calcium urolithiasis in humans--does it have an abettor role in oxalate, and calcium oxalate crystallization?

The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is not clear. We evaluated ASC in blood and urine of fasting male patients with idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller subgroups, we also evaluated their response to exogenous ASC [either intravenous or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test meal. The influence of ASC on calcium oxalate crystallization, the morphology of crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine incubation on urinary oxalate at these pHs, without and with addition of ASC, were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from fasting patients remained unchanged, but the slope of the regression line of urinary ASC versus urinary oxalate was steeper than in the controls; the plasma ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the ASC-supplemented meal caused an increase in the integrated plasma oxalate in the normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were increased, but urinary glycolate was unchanged. In the controls, oral ASC did not affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal growth. In control urine calcium oxalate dihydrate and calcium oxalate monohydrate develops, while in ICU urine only the former crystal type develops. In vitro oxalate neoformation from ASC did not occur. It was concluded that (1) under normal conditions an abettor role of ASC for renal stones is not recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of exogenous ASC is exhibited, and that this is most likely unrelated to an initial increase in oxalate biosynthesis, and (3) ASC appears to modulate directly calcium oxalate crystallization in ICU, although the true mode of action is still not known.

Administration, Oral↗
PubMed2000

Geographic heterogeneity of cellular characteristics of acute myeloid leukemia: a comparative study of Australian and Japanese adult cases.

We assessed a large number of adults (368 from Australia and 494 from Japan) with de novo acute myeloid leukemia (AML) to define the biological differences between the two populations. In this study, AML was classified using the French-American-British (FAB) criteria into seven groups (M1-M7). M2 was more common in Japan than in Australia, whereas M4 occurred more frequently in Australia than in Japan. Other FAB subtypes were evenly distributed. Cytogenetically, Japanese M2 displayed a higher frequency of t(8;21) than Australian (33.1% vs 15.3%, P < 0.05). The t(15;17), inv/del(16), 11q23 aberrations and 5/7/8 abnormalities were seen at similar frequencies. Immunophenotypically, Japanese M4/M5 more frequently displayed CD13 and CD14 than Australian, whereas the stem cell markers, CD34 and HLA-DR were observed at a relatively higher rate in Australian M3 than in Japanese M3. The B cell antigen, CD19 was more frequently seen in Japanese M2 than in Australian M2, but found more often in Australian M5 than in Japanese M5. In both populations, a close relationship was observed between the expression of CD19 and t(8;21). These findings suggest different biological characteristics of AML between the two populations, the main differences being generated by a higher frequency of t(8;21) chromosomal abnormality in Japanese AML. Leukemia(2000) 14, 163-168.

Acute Disease↗
PubMed2000

On the direct Fourier method for computer tomography.

The paper considers the direct Fourier methods (DFM's) for reconstructing an image from its given X-ray projections. The main purpose here is to use concepts from numerical analysis to estimate the errors in the methods. We also suggest an alternative to the interpolations involved in the DFM's and estimate the number of terms involved. Realizing that one of the main reasons for the degradation of the quality of the reconstruction is the Gibbs phenomenon, we suggest a way to overcome this difficulty and give numerical evidence of its efficacy.

Algorithms↗
PubMed2000

Like a terrorist.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1999

The DPL1 gene is involved in mediating the response to nutrient deprivation in Saccharomyces cerevisiae.

Sphingosine-1-phosphate is a sphingolipid metabolite involved in the regulation of cell proliferation in mammalian cells. The major route of sphingosine-1-phosphate degradation is through cleavage at the C, bond by sphingosine phosphate lyase. The recent identification of the first dihydrosphingosine/sphingosine phosphate lyase gene in Saccharomyces cerevisiae establishes that phosphorylated sphingoid base metabolism is conserved throughout evolution. The dpl1delta deletion mutant, which accumulates endogenous phosphorylated sphingoid bases, exhibits unregulated proliferation upon approach to stationary phase. The increased proliferation rate during respiratory growth was associated with failure to appropriately recruit cells into the G1 phase of the cell cycle. Several genes were found to be overexpressed or prematurely expressed during nutrient deprivation in the dpl1delta strain, including glucose-repressible genes and G1 cyclins. These studies implicate a role for DPL1 and phosphorylated sphingoid bases in the regulation of global responses to nutrient deprivation in yeast.

Aldehyde-Lyases↗
PubMed1999

Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallization in urine: observations in patients with recurrent idiopathic calcium urolithiasis.

The effects of magnesium (Mg) and citrate on the metastable limit of calcium oxalate (CaOx) solubility (synonym: tolerable oxalate TO) were examined in artificial urine and in postprandial urine of male patients with idiopathic calcium urolithiasis (ICU). In artificial urine increasing pH, Mg and citrate elevate TO, decrease CaOx supersaturation only marginally, but elevate considerably free citrate; the effect of Mg alone was small in comparison with citrate alone, and the effects of both substances appeared additive. In ICU patients, matched for sex, age and CaOx supersaturation to non-stone-forming controls, TO was decreased (mean values 0.33 vs. 0.52 mM/l in controls, P < 0.05). Additional significant (P < 0.05) differences were found between ICU and controls: the former exhibited increased CaOx crystal growth, decreased crystal agglomeration time, a more acidic urinary pH, increased concentrations of free calcium and free Mg, and decreased free oxalate and free citrate. After ingestion of a urine-acidifying test meal, or this meal supplemented with either neutral Mg citrate or Mg-alkali citrate, by three groups of male ICU patients, matched for age and CaOx supersaturation, only the last-named preparation evoked an increase in TO and a decrease in crystal diameter, while the normally occurring pH decline from fasting urine was virtually abolished, and the ratios urinary Mg/citrate and calcium/citrate tended towards low values. In contrast, Mg citrate increased crystal agglomeration time, while changes in the other parameters were only insignificant. The crystals formed in urine were CaOx di- and monohydrate (by electron microscopy), and energy dispersive X-ray analysis showed calcium peaks exclusively. However, chemical analysis of crystals verified the presence not only of oxalate and calcium, but also of Mg, phosphate, citrate, and urate; moreover, these crystal constituents seemed to be influenced by Mg citrate and Mg-alkali citrate in different ways. It was concluded that (1) Mg and citrate are effectors of TO in artificial and natural urine; (2) in ICU, low TO and other disturbed CaOx crystallization parameters appear related to the prevailing low urinary pH and low free citrate; (3) Mg-alkali citrate inhibits CaOx crystallization, probably via actions of the citrate, but not the Mg. Because of the eminent role of Mg in human health and ICU, further studies on crystallization after oral intake of Mg in the form of citrate are warranted.

Calcium Oxalate↗
PubMed1998

VLA-4 is involved in the engraftment of the human pre-B acute lymphoblastic leukaemia cell line NALM-6 in SCID mice.

Attachment of human pre-B leukaemic cells to human or murine bone marrow stromal cells in vitro is largely mediated by the beta1 integrin VLA-4 binding to VCAM-1. Cells subsequently migrate within the stroma, a process also involving VLA-4. A variant of the pre-B acute lymphoblastic leukaemia cell line NALM-6, designated 4A1, lacking expression of VLA-4, was generated by radiation-induced mutagenesis followed by several rounds of negative selection with immunomagnetic beads, fluorescence activated cell sorting and clonal expansion. In vitro assays using 4A1 cells showed reduced binding to, and migration under, the murine stromal line M2-10B4. Sublethally irradiated mice (n=19) with severe combined immunodeficiency were injected intravenously with NALM-6 cells. Animals developed signs of leukaemia with hind-limb paralysis at a median of 30 d (95% confidence interval 28-30). Although there were no gross abnormal findings at autopsy, histological analysis revealed extensive marrow replacement and focal liver infiltration with leukaemic blasts, which were confirmed to be of human origin by flow cytometry. 12 mice were injected with a similar number of cells from the VLA-4-negative variant cell line 4A1. Six mice developed signs of leukaemia after 43-74d, with the remaining six being free of signs of disease after > 100d (P<0.001). Mice in this group with leukaemia had a lower incidence of hind-limb paralysis and less leukaemic infiltration in the marrow, but in some cases had large tumour nodules elsewhere. After a single 500 microg intraperitoneal injection of anti-murine VCAM-1 monoclonal antibody (MK2.7), five additional mice were injected with an identical number of wild-type (VLA-4+) NALM-6. All animals developed signs of leukaemia after a similar period to those injected with wild-type NALM-6 only. These results demonstrate that the beta1 integrin VLA-4 is involved in the engraftment of the pre-B-cell leukaemic cell line NALM-6 in SCID mice, although the interaction with VCAM-1 is unlikely to be the sole explanation.

Animals↗