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Biomedical subjects

A Salam

Publications and source records attributed to A Salam.

At least 37 records · Page 2Linked to original sources
PubMed2001

Radiological features of hepatocellular carcinoma in Southern Pakistan.

We describe the radiological features of 201 patients diagnosed as having hepatocellular carcinoma (HCC) in Southern Pakistan. The cases of biopsy-proven HCC were analysed retrospectively for years 1994-1998. Age, sex, underlying cirrhosis, hepatitis markers, and radiological description were recorded. The mean age was 56 years. There were 149 males and 52 females. 82% patients had underlying cirrhosis. The tumour size was measured in at least two dimensions, and the maximum mean tumour size at the time of diagnosis was 8.3 +/- 4.0 cm. Of the tumours 79.5% were more than 5 cm; 56% of primary HCC were multifocal; 51% involved the right lobe only; 15% involved the left lobe; 34% involved both lobes of liver. Portal vein thrombosis was detectable in 17%. There were no significant differences in the radiological patterns amongst patients who had hepatitis B virus related and hepatitis C virus-related HCC except for age.

Adult↗
PubMed2001

A survival analysis of metastatic breast cancer in Pakistani patients.

OBJECTIVE: To determine the overall survival of metastatic breast cancer in the Pakistani patients and compare it with published information. METHOD: The design was a retrospective analysis of metastatic breast cancer patients from breast cancer database. A total of 137 patient based information was available for review and analysis. RESULTS: An overall median survival of 2.83 years was noted in metastatic breast cancer patients. CONCLUSION: This survival figure in this study compares favorably to those published in the literature.

Adult↗
PubMed2001

Lack of correlation between alpha-fetoprotein and tumor size in hepatocellular carcinoma.

OBJECTIVE: To determine whether there was a correlation between tumor size and alpha feto-protein (alpha-FP) levels in hepatocellular carcinoma. SETTING: Retrospective study in tertiary referral center with specialist Oncology services in Southern Pakistan. SUBJECTS: Consecutive patients with biopsy-proven hepatocellular carcinoma diagnosed between January 1994 and June 1998. MAIN OUTCOME MEASURES: Correlation between alpha-FP levels and maximum tumor diameter. RESULTS: The mean tumor size was 8.3 +/- 4.2 cm. The mean alpha-FP level was 17,027 ng/ml. Twenty four percent patients had an alpha-FP level which was within the normal limits (< 10 ng/ml). There was no correlation between tumor size and alpha-FP levels (r = -0.155; p = 0.129). CONCLUSION: There was no correlation between the tumor size and alpha-FP levels.

Analysis of Variance↗
PubMed2000

Factors which predict unsuccessful mobilisation of peripheral blood progenitor cells following G-CSF alone in patients with non-Hodgkin's lymphoma.

INTRODUCTION: High-dose therapy with haematopoietic progenitor cell support has increasingly been utilised for patients with haematological malignancies. Peripheral blood is the stem cell source of choice, however, various mobilisation strategies are used by different centres. PATIENTS AND METHODS: Over a 2-year period, 52 patients with non-Hodgkin's lymphoma (median age 47 years, range 16-64 years) underwent peripheral blood progenitor cell mobilisation using G-CSF alone (16 microg/kg/day). The harvest was considered successful if > or =1 x 10(6) CD34(+) cells/kg were collected by leukapheresis. The histological subtypes of non-Hodgkin's lymphoma comprised: follicular (24 patients), diffuse large B-cell (14 patients), lymphoplasmacytoid (four patients), mantle cell (three patients), lymphoblastic lymphoma (one patient) and small lymphocytic lymphoma/chronic lymphocytic leukaemia (six patients). The median interval from diagnosis of non-Hodgkin's lymphoma to mobilisation was 27 months (range 2 months to 17 years). The median number of prior treatment episodes was 2 (range 1-5); 26 patients had received fludarabine alone or in combination. At the time of peripheral blood progenitor cell mobilisation, 20 patients were in 1st remission and 32 were in > or =2nd remission; 30 patients were in partial remission and 22 were in complete remission; the bone marrow was involved in nine patients. RESULTS: Peripheral blood progenitor cell mobilisation/harvest was unsuccessful in 19 out of 52 (37%) patients (mobilisation: 18, harvest: 1). The factors associated with unsuccessful mobilisation or harvest were: prior fludarabine therapy (P=0.002), bone marrow involvement at diagnosis (P=0.002), bone marrow involvement anytime prior to mobilisation (P=0.02), histological diagnosis of follicular, mantle cell, or lymphoplasmacytoid lymphoma, or small lymphocytic lymphoma/chronic lymphocytic leukaemia (P=0.03) and female gender (P=0.04). CONCLUSION: Although peripheral blood progenitor cells can be successfully mobilised and harvested from the majority of patients with non-Hodgkin's lymphoma after treatment with G-CSF alone, the latter is unsuccessful in approximately one-third of patients. These factors should be taken into account when patients are being considered for high-dose treatment.

Adolescent↗
PubMed2000

High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up.

PURPOSE: To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements. PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti-B-cell antibodies and complement. RESULTS: Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P =.04) and three or fewer treatment episodes before HDT (HR, 0.03; P =.001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P <.001) and death (HR, 0.25; P =.02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome. CONCLUSION: Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.

Adult↗
PubMed2000

Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies.

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P =.009) and older age (P =.02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P =.05 and.07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

Adolescent↗
PubMed1999

Marked mitigation of transplant vascular sclerosis in FasLgld (CD95L) mutant recipients. The role of alloantibodies in the development of chronic rejection.

BACKGROUND: In the acute rejection of allografts, the interaction between Fas (CD95) and its ligand (FasL; CD95L) has been shown to be involved in mediating apoptotic cell death. The role, however, of these molecules in the pathogenesis of transplant vascular sclerosis is as yet undetermined. The present study was therefore designed to address this issue. MATERIAL: C3H/HEJ FasLgld (FasL-; H2k) spontaneously mutant mice were used either as donors or recipients of aortic allografts; wild-type C57B1/6 (B6; H2b) were used as corresponding recipients or donors (n=6/group), respectively. Controls included aortas transplanted across appropriate allogeneic and syngeneic strain combinations. For histopathological evaluations, the grafts were harvested at day 40 after transplantation, at which time, splenocytes and sera were also obtained for mixed leukocyte reaction and complement-mediated microcytotoxicity assays, respectively. RESULTS: Similar to aortas obtained from allogeneic controls, allografts harvested from FasL- -->B6 recipients had morphological evidence of chronic rejection characterized by circumferential intimal thickening with partial disruption of the elastic membranes. Correspondingly, heightened antidonor cellular reactivity was also witnessed in these recipients. On the contrary, B6 allografts harvested from the majority of C3H-->FasL- recipients exhibited marked preservation of aortic morphology. Although these recipients had diminished antidonor cellular proliferation, the titers of alloantibodies were markedly elevated. CONCLUSION: The presence of FasL-expressing functional cytotoxic T cells is required for the pathogenesis of transplant vascular sclerosis. The significant reduction and/or absence of chronic rejection with the concomitant retention of antidonor humoral response in C3H FasL- recipients of B6 aortas prompt us to suggest that perhaps posttransplantation vasculopathy is initiated by cell-mediated cytotoxicity with its perpetuation facilitated by alloantibodies.

Animals↗
PubMed1999

The clinical pattern of HER-2/neu oncogene overexpressing breast cancer in Pakistani patients at initial presentation: an analysis of HER-2/neu positive versus negative disease--a preliminary report.

BACKGROUND: HER 2/new oncogene is an important prognostic marker in Breast Cancer and has implications in therapy planning. OBJECTIVE: To describe the clinical features of HER 2/new positive and negative Breast Cancer in the Pakistani patient population and note clinical differences between the two groups if any. DESIGN: A retrospective analysis of Breast Cancer cases at the Aga Khan University, Hospital. METHOD: Immunochemical staining on formation fixed paraffin embedded tissue using oxidase antiperoxidase method. A total of 152 Breast cancer tissue samples were tested for HER-2/neu gene presence. Of these 43 (39%) samples tested positive and 109 (61%) tested negative. A comparison of the two groups revealed that only a few factors tested for either significance or borderline statistical significance between the two groups. These factors included the estrogen receptor status and the number of lymph nodes involved in the axilla. The progesterone receptor status was of borderline significance. CONCLUSION: Given the large number of factors tested it appears that there is no consistent defining feature which helps to separate HER-2/neu positive versus HER-2/neu negative cases with Breast Cancer.

Adult↗
PubMed1998

Use of the polymerase chain reaction and direct sequencing analysis to detect cells with the t(14;18) in autologous bone marrow from patients with follicular lymphoma, before and after in vitro treatment.

Between August 1993 and February 1994, 25 patients with follicular or transformed follicular lymphoma had bone marrow harvested at St Bartholomew's Hospital (SBH) with a view to proceeding to high-dose treatment comprising: cyclophosphamide 60 mg/kg x 2 and total body irradiation, 200 cGy x 6, supported by autologous bone marrow transplantation (ABMT). The marrow mononuclear cell fraction was treated in vitro with four anti-B cell antibodies and baby rabbit complement. The aim of this study was to determine whether in vitro treatment of the marrow could remove morphologically undetectable lymphoma cells. PCR analysis for the t(14;18) was used to determine the presence or absence of lymphoma. At the time of the bone marrow harvest, 21/25 bone marrow samples were positive for the t(14;18), in 15/22 patients, the rearrangement could also be demonstrated in peripheral blood. After in vitro treatment, 18/21 samples (86%) remained 'PCR positive'. Sequence analysis of the t(14;18) PCR products was performed on the latter and on lymph node biopsy material taken at diagnosis from 12 patients. The same t(14;18) sequences were found in the bone marrow harvest samples as in the patients' original biopsies. These results suggest that this form of in vitro treatment does not completely eradicate the t(14;18) bearing clone. New and better methods need to be developed.

Adult↗
PubMed1997

Presence of intrinsic B lymphocyte tolerance in mixed but not in complete semiallogeneic bone marrow chimeras.

The existence of intrinsic B lymphocyte transplantation tolerance was investigated in murine semiallogeneic complete and mixed bone marrow chimeras. Complete chimeras (CC), which were obtained by infusing 20x10(6) C57BL/10 (P1) bone marrow (BM) cells into irradiated (10.5 Gy) (C57BL/10xBALB/c) F1 recipients, were repopulated for 100% with P1 lymphohematopoietic cells. In mixed chimeras (MC), which were obtained by injection of 15 x 10(6) P1 together with 5 x 10(6) F1 BM cells, between 15% and 40% of F1 lymphohematopoietic cells persisted after BM transplantation. Neither MC nor CC were able to develop significant T cell immunity (mixed lymphocyte reaction) or B cell immunity (IgG alloantibodies) against the mismatched host antigens (BALB/c), despite repetitive immunizations. However, after immunization with third-party cells (C3H), the IgG alloantibodies raised cross-reacted with the host-type (BALB/c) antigens in the CC but not in the MC. This suggested that intrinsic B lymphocyte tolerance for host antigens had occurred in MC but not in CC. This was further evidenced in transfer experiments using lethally irradiated C57BL/10 mice reconstituted with purified control C57BL/10 T lymphocytes together with purified C57BL/10 B lymphocytes isolated from CC or MC. Only the recipients reconstituted with B lymphocytes from CC, and not those from MC, produced anti-BALB/c IgG alloantibodies after immunization. These results show that intrinsic B lymphocyte tolerance can be achieved after transplantation and that this depends on the presence of lymphohemopoietic cells expressing the tolerogens.

Animals↗
PubMed1996

Graft-versus-host reactivity and graft-versus-leukemia effect in murine allogeneic bone marrow chimeras conditioned with total body irradiation or total lymphoid irradiation.

To investigate whether graft-versus-host reactivity (GVHR) and the graft-versus-leukemia (GVL) effect can be differentiated, C3H-->AKR mixed bone marrow (BM) chimeras were prepared using two different conditioning regimens. Total body irradiation (TBI) chimeras were induced by infusing 5 x 1O(6) T cell depleted syngeneic AKR BM cells together with 15 x 1O(6) non T cell depleted allogeneic C3H BM cells 1 day after a single fraction of 10.5 Gy TBI. Total lymphoid irradiation (TLI) chimeras were prepared by injecting only 15 x 10(6) non T cell depleted C3H BM cells after 10 daily fractions of 2 Gy TLI Both groups of chimeras were healthy, without clinical or histological signs of graft-versus-host disease (GVHD). In both groups, clonal deletion of antihost-reactive donor type T lymphocytes was found. Whereas TBI chimeras did resist rejection by host type splenocytes injected 2 months after transplantation, TLI chimeras did not. As the latter phenomenon is believed to reflect remaining GVHR, TLI chimeras did have a lower remaining GVHD capacity than TBI chimeras. Nevertheless, TLI chimeras survived significantly longer after host type leukemia challenge (injection of 6 x 10(6) AKR lymphoma cells). The better survival of the TLI chimeras was not due to the radiation regimen, because TLI or TBI conditioned syngeneic AKR-->AKR BM recipients did succumb equally rapidly after AKR lymphoma injection. Donor type (CM) lymphokine-activated killer cell activity, however, was higher in TLI chimeras and may explain the better GVL activity in TLI mice. This model thus illustrates that GVHD and GVL effects can be dissociated and are differentially influenced by the conditioning regimen used for BM transplantation.

Animals↗
PubMed1995

Why treatment centres failed to prevent cholera deaths among Rwandan refugees in Goma, Zaire.

In July, 1994, in one of the worst cholera outbreaks in recent times, an estimated 12,000 Rwandan refugees died in Goma in eastern Zaire. The Vibrio cholerae strains were resistant to tetracycline and doxycycline, the commonly used drugs for cholera treatment. Despite the efforts of international organisations, which provided medical relief by establishing treatment centres in Goma, mortality from the disease was much higher than expected. In the area of Muganga camp, which had the largest concentration of refugees and where most of the medical aid organisations were active, the highest reported case-fatality ratio for a single day was 48%. The slow rate of rehydration, inadequate use of oral rehydration therapy, use of inappropriate intravenous fluids, and inadequate experience of health workers in management of severe cholera are thought to be some of the factors associated with the failure to prevent so many deaths during the epidemic. In one of the temporary treatment centres with the worst case-fatality record, our team showed that improvement of these factors could increase the odds of survival of cholera patients even in a disaster setting.

Ambulatory Care Facilities↗
PubMed1995

Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support in patients with haematological malignancy.

BACKGROUND: Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support is increasingly being used in patients with haematological malignancy considered to be at high risk for recurrence. The results of this approach, in comparison with the previous experience at St. Bartholomew's Hospital (SBH) using autologous bone marrow transplantation form the basis of this report. PATIENTS AND METHODS: 42 patients (age range 18-63 years, median 42 years), deemed to have a poor prognosis with conventional therapy received myelo-ablative therapy with PBPC support. Diagnoses comprised: non-Hodgkin's lymphoma (NHL): 16 patients, Hodgkin's disease (HD): 9, Multiple Myeloma (MM): 12, and solid tumours (ST): 5. PBPC were mobilised using adriamycin: 35 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 orally, days 1-5, followed by G-CSF: 5 micrograms/kg, subcutaneously, for a median of 7 days (range 6-9 days). RESULTS: A total of 67 PBPC collections were performed, 1 being 'sufficient' (i.e. mononuclear cells > or = 1.5 x 10(8)/kg and CD34+ cells > or = 1 x 10(6)/kg) in 21 of the 42 patients. The median time to haematological recovery following reinfusion of PBPC was 13 days for both neutrophils > 0.5 x 10(9)/l and platelets > 20 x 10(9)/l (ranges: 8-27, and 8-48 days, respectively) which is significantly shorter than for patients in the historical control group. Supportive care requirements were also significantly reduced, as was the duration of hospital stay i.e., median 19 days (range 12-73 days) compared with 29 days (range 9-180 days). CONCLUSION: These results confirm rapid blood count recovery following myelo-ablative therapy with PBPC support and the feasibility of this approach.

Adolescent↗
PubMed1995

Induction of CD80 expression in low-grade B cell lymphoma--a potential immunotherapeutic target.

The CD80 antigen (B7) is expressed on activated B lymphocytes. It is thought to be important in eliciting a T cell response via its ligands CD28 and CTLA-4 when antigen is presented in the presence of the MHC-1 peptide. Low-grade B cell lymphomas analysed by flow cytometry express CD80 very poorly. However, when grown in vitro using the IL-4/anti-CD40 stromal cell culture system, following depletion of T and IgD-bearing cells, a monoclonal B cell expansion occurs. Cells harvested at days 10-13 express the antigen strongly, regardless of the histological subtype of lymphoma. Further investigation of CD80-mediated immune functions may be possible using this system as a basis for testing immunotherapy.

B7-1 Antigen↗
PubMed1994

Clonal deletion and clonal anergy in allogeneic bone marrow chimeras prepared with TBI or TLI.

The evolution of Vbeta6-expressing C3H (H2k, Thy 1.2, Mls a-) lymphocytes was investigated in C3H recipients mice pretreated with total body irradiation (TBI) or total lymphoid irradiation (TLI) and infusion of AKR (H2k, Thy 1.1, Mls a+) cells. After TBI (9.5 Gy) all Vbeta6+ Thy 1.2 (C3H) cells, which are capable of reacting against the Mls a antigen that like expressed by AKR mice, were deleted in the thymus and the periphery in stable bone marrow (BM) chimeras obtained by infusion of 5 x 10(6) T-cell-depleted (TCD) AKR BM cells. When, in the opposite combination, 30 x 10(6) C3H spleen cells were infused into TBI-treated AKR cells, all animals developed graft-versus-host disease (GVHD) with no clonal deletion and in contrast, showed an increase in Vbeta6+ C3H cells. After injection of 30 x 10(6) AKR BM cells into TLI-treated C3H mice no C3H cells were detected in the thymus and only a small percentage in the periphery. Within these C3H cells Vbeta6+ cells were only partially deleted and anergized as they did not respond in vitro after stimulation with Mls a+ AKR cells or anti-Vbeta6 mAb. Cells suppressing anti-Mls a-reacting C3H cells were not found. After injection of 15 x 10(6) AKR cells more C3H cells were found in the thymus, but only a minority of Vbeta6+ cells persisted in the periphery of these animals. In conclusion in TBI-prepared chimeras only clonal deletion occurred, whereas in TLI-prepared chimeras both clonal deletion and anergy occurred in maintaining tolerance.

Animals↗