Search PubMed⌕ Search

Biomedical subjects

N Jamal

Publications and source records attributed to N Jamal.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative assessment of breast density from digitized mammograms into Tabar's patterns.

We describe a semi-automated technique for the quantitative assessment of breast density from digitized mammograms in comparison with patterns suggested by Tabar. It was developed using the MATLAB-based graphical user interface applications. It is based on an interactive thresholding method, after a short automated method that shows the fibroglandular tissue area, breast area and breast density each time new thresholds are placed on the image. The breast density is taken as a percentage of the fibroglandular tissue to the breast tissue areas. It was tested in four different ways, namely by examining: (i) correlation of the quantitative assessment results with subjective classification, (ii) classification performance using the quantitative assessment technique, (iii) interobserver agreement and (iv) intraobserver agreement. The results of the quantitative assessment correlated well (r2 = 0.92) with the subjective Tabar patterns classified by the radiologist (correctly classified 83% of digitized mammograms). The average kappa coefficient for the agreement between the readers was 0.63. This indicated moderate agreement between the three observers in classifying breast density using the quantitative assessment technique. The kappa coefficient of 0.75 for intraobserver agreement reflected good agreement between two sets of readings. The technique may be useful as a supplement to the radiologist's assessment in classifying mammograms into Tabar's pattern associated with breast cancer risk.

Absorptiometry, Photon↗
PubMed2004

Bone marrow aspirates as part of routine donor assessment for allogeneic blood and marrow transplantation can reveal presence of occult hematological malignancies in otherwise asymptomatic individuals.

Pre transplant screening work-up of donors for allogeneic blood and marrow transplantation is essential in an effort to minimize risks to the recipient and protect the donor. At Princess Margaret Hospital, every potential donor is screened with a bone marrow aspirate. The case histories of three asymptomatic potential donors who presented within 1 year with normal complete blood counts, history and physical examination are presented. A 65-year-old male patient was diagnosed with smouldering multiple myeloma, a 72-year-old male patient with chronic lymphocytic leukemia and a 42-year-old male patient with myelodysplastic syndrome. Bone marrow examination led to the diagnosis in each one of these cases. Of note is that each of the potential donors was discovered to have the same disease as the transplant recipient. In vitro clonogenic hemopoietic progenitor assays were compared to those of 20 normal volunteers. Inferior growth of hemopoietic progenitor colonies in all three was noted. In conclusion, particularly in older donors and donors with potential for familial malignancies, more screening investigations including bone marrow aspiration may be reasonable to investigate for occult hematological malignancies prior to stem cell donation. Clonogenic assays can contribute to detect hemopoietic abnormalities pre transplant.

Adult↗
PubMed2003

A study of mean glandular dose during diagnostic mammography in Malaysia and some of the factors affecting it.

The primary objective of this study was to determine the mean glandular dose (MGD) during diagnostic mammography in Malaysia. The secondary objective was to evaluate some of the factors affecting MGD. A survey of standard MGD was performed, based upon quality control records for the period October 1999 to August 2001. This covered 30 mammography units from 9 manufacturers. MGD was also measured for a series of patients attending mammography examinations at three other mammography units. MGD per film was estimated from recorded radiographic factors, the compressed breast thickness (CBT) and X-ray unit calibration data. MGD per woman was calculated by summing the MGDs for all films, and averaging it over both breasts. 300 women drawn equally from three major ethnic groups, namely Malay, Chinese and Indian, took part in the study. The difference of MGD per woman between ethnic groups was tested for significance using non-parametric Kruskal-Wallis and median tests. The factors affecting MGD per woman were tested for significance using a multivariate analysis of variance. The MGD for the phantom was 1.23 mGy (range 0.22-2.39 mGy) while the mean patient based MGD per film was 1.54 mGy and 1.82 mGy for the craniocaudal and mediolateral oblique views, respectively. The mean MGD per woman was 3.37 mGy. It was also found that there is no significant difference in MGD per woman among the ethnic groups (p>0.05, Kruskal-Wallis test). However, on the multivariate test two factors, namely half value layer of the X-ray beam and (CBT), had a significant effect on MGD per woman (p<0.05). No significant relationships were seen between MGD per woman with respect to ethnicity, body mass index or age.

Adult↗
PubMed2002

Long-term medical outcomes and quality-of-life assessment of patients with chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow transplantation.

PURPOSE: Benchmark analysis of patients with chronic myeloid leukemia (CML) alive for more than 10 years after allogeneic bone marrow transplantation (BMT) including data on disease status, bone marrow reserve, long-term complications, and quality of life (QOL). PATIENTS AND METHODS: Eighty-nine patients (46 in first chronic phase, 43 in advanced phase) received an allogeneic BMT for CML during the study period. Medical outcomes and QOL of patients were analyzed retrospectively. RESULTS: Twenty-eight (31.5%) of 89 patients were alive at 10 years and included in this analysis. Thirteen (46.4%) of 28 long-term survivors never relapsed. Fifteen patients relapsed between 0.5 and 16 years after transplantation. Ten patients showed a hematologic relapse and received salvage treatment. Five patients showed transient low levels of BCR-ABL-positive cells by Southern blot with no subsequent hematologic relapse. One of the 28 patients died in blast crisis at 12 years. The most frequent long-term complications were chronic graft-versus-host disease, osteoporosis, and cataracts. Frequency of clonogenic progenitors remained persistently decreased. QOL assessment yielded lower scores in physical performance as compared with an age-matched normative population, whereas social functioning was equivalent. A high degree of satisfaction was noted with interpersonal relationships. CONCLUSION: Patients with CML surviving their BMT long term do well in terms of medical outcomes. A constant rate of relapse was noted, with a high salvage rate of affected patients, suggesting the need for lifelong monitoring. QOL is perceived as good, particularly as related to social functioning; however, it is inferior to a normative population with regard to physical performance.

Adult↗
PubMed2001

Prostate cancer cells induce osteoblast differentiation through a Cbfa1-dependent pathway.

Metastases from prostatic adenocarcinoma (prostate cancer) are characterized by their predilection for bone and typical osteoblastic features. An in vitro model of bone metastases from prostate cancer was developed using a bicompartment coculture system of mouse osteoblasts and human prostate cancer cells. In this model, the bone-derived prostate cancer cell lines MDA PCa 2a and MDA PCa 2b induced a specific and reproducible increase in osteoblast proliferation. Moreover, these cells were able to induce osteoblast differentiation, as assessed by increased alkaline phosphatase activity, Osteocalcin expression, and calcified matrix formation. This osteoblastic reaction was confirmed in vivo by intrafemoral injection of MDA PCa 2b cells into severe combined immunodeficiency disease mice. In contrast, the highly undifferentiated, bone-derived human prostate cancer cell line PC3 did not produce an osteoblastic reaction in vitro and induced osteolytic lesions in vivo. The osteoblast differentiation induced by MDA PCa 2b cells was associated with up-regulation of the osteoblast-specific transcriptor factor Cbfa1. Moreover, treatment of osteoblasts with conditioned medium obtained from MDA PCa 2b cells resulted in up-regulation of Cbfa1 and Osteocalcin expression. In support of the differentiation studies, a microarray analysis showed that primary mouse osteoblasts grown in the presence of MDA PCa 2b cells showed a shift in the pattern of gene expression with an increase in mRNA-encoding Procollagen type I and Osteopontin and a decrease in mRNA-encoding proteins associated with myoblast differentiation, namely myoglobin and myosin light-chain 2. Taken together, these findings suggest that the bone-derived prostate cancer cells MDA PCa 2a and MDA PCa 2b promote differentiation of osteoblast precursors to an osteoblastic phenotype through a Cbfa1-dependent pathway. These results also established that soluble factors produced by prostate cancer cells can induce expression of osteoblast-specific genes. This in vitro model provides a valuable system to isolate molecules secreted by prostate cancer cells that favor osteoblast differentiation. Moreover, it allows to screen for therapeutic agents blocking the osteoblast response to prostate cancer.

Animals↗
PubMed2001

Measurement of dose to the contralateral breast during radiation therapy for breast cancer: reduction by the use of superflab.

The effect of radiation in regard to breast carcinogenesis is well studied and analysed from data from atomic bomb survivors, patients treated for acute mastitis and tuberculosis patients monitored by fluoroscopy. Therefore the radiation received by the untreated breast during breast irradiation of the other breast, is of concern to clinicians. Using thermoluminescence dosimeters, we have measured the dose received by contraleteral breast of six patients during radiation therapy. Most of the dose received will be from the collimator scatter and leakage. We investigated the effect of an absorber, superflab, in reducing the skin dose to contralateral breast. With the overlaying of a cm superflab on the breast, the skin (surface) dose could be reduced by 40-75% of its original value. This is an effective and practical method of reducing significantly the dose to contralateral breast during breast conservation therapy. Superflab can be made conveniently at low cost.

Breast Neoplasms↗
PubMed1999

Comparative testing of peripheral blood and bone marrow for BCR-ABL transcripts in patients post allogeneic bone marrow transplantation and during interferon treatment for chronic myeloid leukemia.

Patients with CML post allogeneic BMT or during treatment with Interferon were monitored in bone marrow and peripheral blood for BCR-ABL transcripts by RT-PCR and in the majority of cases also by Southern blotting. Bone marrow and peripheral blood samples were obtained simultaneously and tested by RT-PCR with the objective to determine the usefulness to follow CML patients by testing peripheral blood rather than bone marrow samples. For the purpose of this study we have considered the test results obtained from bone marrow samples as the standard. A total of 111 CML patients were examined who underwent either an allogeneic BMT (n=91) or were treated with Interferon (n=20) amounting to a total of 163 assessments for BCR-ABL. Concordance of results was observed in 153 samples (93.9%). 10 samples showed discordance. Seven of these were subjected to repeat testing by RT-PCR. The previously obtained discordant results were confirmed. The sensitivity of peripheral blood assays was calculated to be 96.2% with a specificity of 89.5%. RT-PCR results restricted to Southern blot negative patients showed concordance of bone marrow and peripheral blood in 91.1% of tested samples with a sensitivity of 92.7% and a specificity of 88.6%. The subset of patients in which Southern blot testing was not available showed concordance at a similar level. Complete concordance was seen in all patients that were found to be positive by Southern blotting. We conclude from this study that peripheral blood testing for BCR-ABL transcripts by RT-PCR is a test with high sensitivity and specificity and may potentially replace bone marrow testing. This approach will probably result in a high level of acceptance by patients and may permit more frequent monitoring.

Blotting, Southern↗
PubMed1998

Clinical and economic analysis of allogeneic peripheral blood progenitor cell transplants: a Canadian perspective.

Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 microg/kg/day) (group 1) and 20 mobilized with 10 microg/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 x 10(6) CD34+/kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34,643 vs $37,354) but the mean overall cost for both groups was similar at 100 days ($46,334 vs $46,083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT.

Bone Marrow Transplantation↗
PubMed1996

Normal and leukemic SCID-repopulating cells (SRC) coexist in the bone marrow and peripheral blood from CML patients in chronic phase, whereas leukemic SRC are detected in blast crisis.

Progress in understanding the abnormal regulation of hematopoiesis in chronic myelogenous leukemia (CML) would be facilitated if neoplastic cells, at all stages of the disease, could be studied in an animal model. In this report, we show that irradiated severe combined immunodeficient (SCID) mice can be transplanted with both normal (Philadelphia chromosome [Ph]-negative) and neoplastic (Ph+) cells from CML patients with either chronic or blast phase disease. Mice transplanted with peripheral blood (PB) or bone marrow (BM) cells from 9 of 12 chronic phase CML patients were well engrafted with human cells including multilineage colony-forming progenitors and CD34+ cells for at least 90 days posttransplantation. Repeated posttransplant injections of cytokines did not enhance the number of engrafted human cells. Interestingly, approximately 70% of the human progenitors found in the engrafted SCID BM were Ph-, suggesting that the growth of primitive normal cells is favored in this in vivo transplant model. A similar number of normal cells were found in mice transplanted with either PB or BM cells, suggesting that elevated numbers of primitive normal cells are present in CML PB. When cells from patients with CML in either myeloid or lymphoid blast crisis were transplanted into SCID mice, the BM of these mice was more rapidly repopulated and to a higher level than that observed with transplants of chronic phase cells. Moreover, all human colony-forming progenitors present in the BM of mice transplanted with blast crisis cells were Ph+, and the majority of cells showed the same morphological features of the blast crisis cells originally transplanted. These experiments provide a starting point for the creation of an animal model of CML and establish the feasibility of using this model for the future characterization of transplantable CML stem cells during disease progression.

Animals↗
PubMed1994

Spontaneous remission of polycythemia vera: clinical and cell culture characteristics.

A 20-year-old woman presented with polycythemia vera and was treated with phlebotomy alone for eleven years, following which all clinical manifestations of the disease disappeared. The clinical remission with normal physical findings and normal peripheral blood counts has persisted for a further 11 years. Erythroid colony culture results have paralleled the clinical state. Initial bone marrow cultures revealed spontaneous growth of erythroid burst-forming units (BFU-E). Subsequent cultures of peripheral blood cells throughout most of the period of spontaneous clinical remission have revealed little or no spontaneous growth of BFU-E. This suggests a suppression of the abnormal stem cell clone during the period of remission.

Adult↗
PubMed1994

Determination of IL6, IL1, and IL4 in the plasma of patients with multiple myeloma.

Interleukin 6 (IL6) plasma levels were measured in 63 patients with multiple myeloma and 8 individuals with benign monoclonal gammopathy. 15 of these 71 samples showed by an enzyme linked immunosorbent assay (ELISA) detectable levels that ranged from 5 to 107 pg of IL6/ml. The IL6 levels of patients with multiple myeloma did not differ significantly from those of normal individuals (N = 25, range 5-27 pg IL6/ml) (Student's t-test, p = 0.295). The samples were negative for IL4; 3 were found positive for IL1 beta. A correlation between IL6, IL4 and IL1 beta levels and disease status was not observed for this group of patients.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Allogeneic bone marrow transplantation from a related donor undergoing long-term immunosuppressive and cytotoxic therapy.

We report the case of a patient with acute myeloid leukemia in second remission who received an allogeneic bone marrow transplant from an immunosuppressed HLA-identical sibling donor. The donor was receiving prednisone, azathioprine and cyclosporine for a cadaveric renal allograft. Bone marrow growth in culture from the donor was normal. Engraftment was within normal limits. Moderate acute graft-versus-host disease (GVHD) developed. We suggest that transplants from immunosuppressed donors are feasible and that this does not preclude the development of GVHD.

Antineoplastic Agents↗
PubMed1993

Cell culture assessment of hematopoietic progenitors in bone marrow transplantation.

A number of cell culture techniques are now available to evaluate clonogenic hematopoietic progenitors as well as cell populations that represent an interactive network of cells with regulatory capabilities. Although clonogenic cells in allografts do not appear to be correlated with the time to recovery, they seem to predict their time to engraftment in autografts. However, these cell populations are likely to be only surrogate measurements because a reduction by various purging techniques does not seem to alter the ability of autografts to reestablishing hematopoiesis. Currently, it is not known whether or not these differences may relate to differences in the preparative regimens, graft-versus-host disease prophylaxis, or other differences in the management, such as administration of high concentrations of various antiviral agents. It is also now possible to measure growth factor production following the transplant procedure and to correlate the availability of endogenous factors and recovery after a transplant. Under normal conditions, the activity levels appear to return to normal values within 20-30 days, whereas in patients with late engraftment one may observe prolonged elevation of growth factors. If confirmed, this would suggest that in bone marrow transplants a delayed return is more related to reduced progenitor cells rather than a deficiency of growth factors.

Bone Marrow Transplantation↗
PubMed1993

Clonogenic hematopoietic progenitors and endogenous cytokine production in allogeneic bone marrow transplantation.

The suboptimal return of hematopoietic precursors after bone marrow transplantation is suggestive of a limited bone marrow reserve in recipients of allografts. The problem does not appear to lie in the ability to produce some of the well-known hematopoietic growth factors such as G-CSF or activities considered to stimulate megakaryocytopoiesis. The persistence of factor production in patients with slow returning counts is suggestive of either a defect in the repopulating cells or in the function of the microenvironment that is not reflected in the production of factors that can be measured in the plasma. A defect in the graft may be overcome by altering the composition of engrafting cells. As seen in autologous transplants the addition of peripheral blood stem cells may be effective in reducing the period to engraftment. Putative defects in the microenvironment have to be addressed by further studies. Exogenously added stroma related factors such as kit ligand or IL-11 may be effective in correcting the deficiency.

Bone Marrow Transplantation↗
PubMed1993

Differential sensitivity of human myeloma cell lines and normal bone marrow colony forming cells to a recombinant diphtheria toxin-interleukin 6 fusion protein.

The cytotoxicity of a recombinant interleukin 6 (IL-6)-diphtheria toxin (DT) fusion protein towards human myeloma cell lines was investigated. DAB389-IL-6 inhibited protein synthesis and methylcellulose colony formation by U266 myeloma cells. In the clonogenic assay, the fusion protein approached the level of cytotoxicity achieved by native DT. The specificity of killing by DAB389-IL-6 was demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL-6. The effect of DAB389-IL-6 on colony formation by six OCI-My cell lines was assessed. Similar to U266 cells, colony growth by the OCI-My 5 and -My 2 cell lines was inhibited in a simple dose dependent manner. However, a biphasic effect was observed for the IL-6 dependent OCI-My 4 cells; DAB389-IL-6 stimulated colony formation at low (< or = 10(-11) M) concentrations, yet was inhibitory at higher doses. Three other cell lines whose growth was not altered by IL-6 were relatively unaffected by DAB389-IL-6, despite their sensitivity to native DT. Flow cytometric analysis for IL-6 receptor expression using phycoerythrin-conjugated IL-6 demonstrated specific binding sites on both DAB389-IL-6 sensitive and certain insensitive cell lines, suggesting that other factors in addition to the expression of IL-6 receptors are involved in killing by the fusion toxin. Despite evidence for a role of IL-6 in myeloid cell development, normal bone marrow was insensitive to the IL-6 fusion toxin. In cultures containing both normal bone marrow and U266 cells DAB389-IL-6 effectively inhibited the growth of U266 myeloma colonies but had little effect on normal bone marrow erythroid, granulocyte and mixed erythroid/granulocyte colony growth. From these experiments we conclude that DAB389-IL-6 is specifically cytotoxic towards a subset of IL-6-responsive human myeloma cell lines and may be useful, in some cases, in the selective elimination of tumour cells from mixed populations of normal and malignant cells.

Cells, Cultured↗