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Biomedical subjects

M Khurshid

Publications and source records attributed to M Khurshid.

At least 19 recordsLinked to original sources

Cardiac disease in beta-thalassaemia major: Is it reversible?

INTRODUCTION: The aim of this study was to evaluate the spectrum of cardiac involvement and its outcome in beta-thalassaemia major. METHODS: There were 75 patients with a mean age of 13.8 (+/- 5.5) years, of whom 33 were male and 42 were female. Clinical history, examination and laboratory investigations were assessed. Electrocardiograms, chest radiographs and echocardiograms were reviewed. RESULTS: 44 patients had cardiac involvement in the form of left ventricular systolic dysfunction in 17, diastolic dysfunction in 22, pericardial effusion in 12 and pulmonary hypertension in 12 patients. With intense chelation therapy and cardiac medications, the condition of 13 of 17 patients with systolic dysfunction, and four of 22 with diastolic dysfunction, improved. CONCLUSION: Cardiac disease is a common complication of siderotic disease in thalassaemia major and it can be prevented with regular chelation. This study has shown improved systolic function after regular chelation therapy.

Adolescent↗

Hematologic and cytogenetic findings in eleven chronic myelogenous leukemia patients treated with imatinib mesylate at a tertiary care hospital.

OBJECTIVE: To evaluate the response of Imatinib mesylate in patients with myeloid leukemia in chronic accelerated and blast phase. PATIENTS AND METHODS: Eleven patients with established diagnosis of chronic myeloid leukemia were treated with Imatinib mesylate. Adverse events were documented with regular follow ups. Hematological and cytogenetic responses were assessed according to established criteria. Patients with zero percent Philadelphia positive metaphases were labeled as complete cytogenetic response while patients with 1% to 35% Philadelphia positive metaphases were termed as partial responders. RESULTS: Of 11 cases there were 7 males and 4 females with a mean age of 39.5 years and median age 51 years (range 21-69). Male to female ratio was 7:4. Median follow-up was 34 weeks (range 8-78). Four patients were in blast crisis, 1 in accelerated phase and remaining six patients were in chronic phase. All patients achieved hematological response. Cytogenetic response was present in six patients, 3 were responders and the remaining were non responders. Two patients achieved complete cytogenetic response and one patient had partial cytogenetic response. Both patients with complete cytogenetic response relapsed in twelve weeks time. CONCLUSION: Imatinib mesylate is a drug with curative potential and can be used as a first line drug in the management of CML, however at present the cure rate is unknown.

Adult↗

Prevalence of hepatitis C virus in lymphoproliferative disorders.

OBJECTIVE: To study the prevalence of hepatitis C virus in lymphoproliferative disorders. METHODS: A case control prospective study was performed on 143 patients with lymphoproliferative disorders and 29 patients with non-hematological malignancies were taken as controls. All the patients in both groups were analyzed for various risk factors for infection with hepatitis C virus and were tested for the presence of hepatitis C virus antibody (anti HCV), cryoglobulins and rheumatoid factor antibody. Hepatitis C viremia was documented by detection of HCV RNA by polymerase chain reaction. RESULTS: There was no significant difference for risk factors for hepatitis C virus infection in both the groups except for the increase in number of surgical procedures being carried out in the control group. There was no significant difference in the presence of rheumatoid factor antibody in both the groups and cryoglobulins were not positive in any individual. Five percent patients with lymphoproliferative disorders and 3.4% with non-hematological malignancies were positive for anti HCV. HCV RNA was detected in 29.2% cases and 31.0% in controls. CONCLUSION: There was no association between hepatitis C virus infection and lymphoproliferative disorder in our population. However, further studies are required from this region to establish any causal relationship between hepatitis C virus infection and lymphoproliferative disorder.

Adolescent↗

Polycythemia vera and idiopathic erythrocytosis: comparison of clinical and laboratory parameters.

OBJECTIVE: To evaluate the various clinical and laboratory parameters of Polycythemia vera and idiopathic erythrocytosis in order to differentiate between two entities at the Aga Khan University Hospital. METHODS: Twenty six patients of polycythemia vera and 34 patients of idiopathic erythrocytosis were analyzed with respect to clinical features and laboratory findings. RESULTS: Patients with idiopathic erythrocytosis were males with a mean age of 41 years and no splenomegaly. Patients with polycythemia were older males and females with splenomegaly, red cell count of mor than 6.5 million/cmm, haematocrit 55%, leucocytosis, thrombocytosis and low erythropoietin level. CONCLUSION: Based on the above-mentioned findings, we suggest that polycythemia vera and idiopathic erythrocytosis are separate entities and the diagnosis of these can be made on the basis of clinical and laboratory parameters.

Adult↗

Increased expression of HLA DR2 in acquired aplastic anemia and its impact on response to immunosuppressive therapy.

OBJECTIVE: To study the frequency of HLA DR2 status of patients with aplastic anemia and their response to immunosuppressive therapy at a tertiary care hospital. METHODS: Thirty eight consecutive patients of acquired aplastic anemia were evaluated with respect to demographic features, severity of HLA DR2 status and response outcome to immunosuppressive therapy. RESULTS: The mean age of the patients was 24.6 years + 16.4 with a male to female ratio of 2.8:1. Positivity of HLA DR2 was markedly high in acquired aplastic anemia patients. Twenty four (65%) out of 38 patients as compared to 45 (15%) of 300 healthy controls (p<0.0001) were positive for HLA DR2. Response to immunosuppressive therapy, which included antilymphocyte globulin, cyclosporin and methylprednisolone, was available in sixteen HLA DR2 positive patients and was found satisfactory in 12/16 (75%) patients. CONCLUSION: HLA DR2 was significantly higher in patients with acquired aplastic anemia and favourable response to immunosuppressive therapy was also associated with HLA DR2 positivity.

Adolescent↗

Pulmonary infiltrates during chemotherapy-induced febrile neutropenia: incidence, patterns and outcomes.

OBJECTIVE: To analyze the incidence, etiologies, radiographic patterns, and clinical outcomes of adult leukemics with prolonged febrile neutropenia and pneumonia. METHODS: A retrospective study was conducted at a tertiary care hospital. The medical records of adult patients with acute myeloid leukemia diagnosed between January 1989 and June 2000 and undergoing induction chemotherapy were included. Only the patients who presented with a pulmonary infiltrate, secondary leukemia (e.g., transformed chronic myeloid leukemia underlying myelodysplastic syndrome, or disease following alkylating agent therapy) were included and those developing infiltrates following consolidation chemotherapy were excluded. RESULTS: A total of 124 patients were admitted to the hospital with a diagnosis of AML during the study period. Thirty-one patients were excluded; 93 patients received induction chemotherapy and were included in the study analysis. The median age was 36 years (15 - 70 years); 58 males and 35 females. Sixty two percent patients received Cytosine Arabinoside (Ara-C), 17% received Etoposide, 11% received Ara-C and Mitoxantrone, and 6% received All-trans-retinoic Acid. The mean onset and duration of neutropenia were 5 and 15 days, respectively. Pulmonary infiltrates were identified during 45% of neutropenic episodes. A presumptive causative organism was isolated from 50% of patients with an infiltrate: Gram-positive bacteria were most common (47%) followed by Gram-negative bacilli (33%) and fungi (20%). Survival data were available for 88 patients; median disease free survival for the entire cohort was 7 months. Male sex (p=0.015), onset of neutropenia (p=0.02) and bilateral distribution of an infiltrate (p=0.03) were statistically significant predictors of early mortality. For patients with and without pneumonia, the median disease-free interval and overall survival were 2.5 and 4.6 months and 9 and 13 months (p=0.038 and p=0.095) respectively. CONCLUSION: Neutropenia occurred at a mean of 5.0 after initiation of induction chemotherapy. The majority of patients had bilateral pulmonary infiltrates. Male sex, onset of neutropenia and bilateral distribution of an infiltrate were found to be statistically significant predictors of early mortality.

Acute Disease↗

Frequency of hereditary thrombophilia: an AKUH experience.

OBJECTIVE: To determine the frequency of various causes of hereditary thrombophilia at a referral laboratory and the age and gender distribution. METHODS: This is a descriptive study incorporating a retrospective analysis of requests for thrombophilia screening sent to Clinical laboratory, Aga Khan University Hospital from November 1995 to May 2002. Patients were screened for hereditary causes of thrombophilia including Protein C, Protein S, antithrombin III, Factor V Leiden and homocysteine. Frequency of each disorder; and age and sex distribution was determined. RESULTS: All the patients suspected clinically for thrombophilia were screened. Of the 2825 patients, 70 were diagnosed to have inheritance as a cause of thrombophilia with a frequency of 2.3% for protein C deficiency, 1.4% for protein S deficiency, 1.5% for antithrombin III deficiency, 14.2% for factor V leiden mutation and 2.0% for homocystenemia. CONCLUSION: All the causes of hereditary thrombophilia can be diagnosed by relatively simple laboratory methods, however because of the low frequency of these disorders the screening of general population is not indicated in the absence of clinical symptoms. More prospective studies are required to define the occurrence of these disorders and other causes of thrombosis.

Adolescent↗

Chromosomal abnormalities as a cause of recurrent abortions: a hospital experience.

OBJECTIVE: To analyze the chromosomal abnormalities in couples with history of recurrent abortions. DESIGN: Retrospective study. SETTING: Cytogenetic section, Department of Pathology at the Aga Khan University Hospital, Karachi, Pakistan. PATIENTS: Three hundred couples with history of recurrent abortions. MAIN OUTCOME MEASURE: Structural chromosomal abnormalities in carrier couples. RESULTS: G-banded chromosomes were analyzed from both partners of 300 couples who had had two or more spontaneous abortions. Sixteen (5.3%) couples showed a chromosomal aberration in one of the partners. Seven translocations, 5 inversions, 2 deletions and 2 sex chromosomal abnormalities were identified. There was an increase in structural aberations, which was not significantly different from that reported worldwide. CONCLUSION: Chromosomal analysis is advocated as a primary tool in the evaluation of couples with repetitive fetal wastage.

Abortion, Habitual↗

Outcome of adult acute lymphoblastic leukemia: a single center experience.

OBJECTIVE: To study the outcomes of adult patients with acute lymphoblastic leukemia. SETTING: Tertiary care hospital. STUDY DESIGN: Retrospective analysis. METHODS: Fifty eight adult patients (age >14 years) diagnosed as cases of acute lymphoblastic leukemia were studied with respect to their clinical, morphological and immunopathological features at presentation and their relationship with treatment outcomes. RESULTS: Forty five (77.5%) of the patients belonged to younger age group with male preponderance. The median age was 20 years and mean age was 25.1 years. Male to female ratio was 3:1. Common presenting signs were lymphadenopathy (17.2%), hepatomegaly (32.7%) and splenomegaly (62%). Laboratory features at presentation revealed: hemoglobin > or = 10 gm/dl in 18 (31%), WBC >50 x 10E9 / L in 18 (31%), LDH more than 1000 IU/L in 44 (75.8%) of patients. Morphology revealed that FAB L1 was seen in 21(37.2%) and L2 in 62 (32.7%). Immunophenotyping showed that 26 (61.9%) were early pre-B ALL, 6 (14.2%) were pre-B ALL and T-ALL were 10 (23.8%). Univariate analysis showed age more than 30 years, male gender, total leucocyte count >50 x 10(9)/L and hemoglobin more than 10 gm/dl to be risk factors for poor outcome. Multivariate analysis revealed age more than 30 years, male sex and total leucocyte count > 50 x 10(9)/L are independent risk factors for poor survival. Patients were treated according to the MRCUKX and XII adult protocols. Thirteen (22.4%) patients died during induction therapy secondary to sepsis and progressive disease whereas 42 (72.4%) patients achieved complete remission. Median survival was 18.6 months and 42% patients were alive at 5-years. CONCLUSION: Overall survival and disease free survival were comparable to those reported in literature. However, age more than 30 years, male gender and total leucocyte count >50 x 10(9)/L had an adverse impact on overall survival.

Adolescent↗

Use of intravenous anti-D in patients with refractory and relapsed immune thrombocytopenic purpura.

OBJECTIVE: To determine the response to i.v. anti-D and its comparison with splenectomy as second line therapy in refractory and relapsed cases of ITP, in the Aga Khan University Hospital, Karachi. METHODS: A total of 23 patients with chronic ITP were treated with either anti-D or splenectomy as second line treatment. The patients were assessed for time to achieve a response to second line treatment, duration of response and adverse events. RESULTS: There were 12 patients in the anti-D group and 11 in the splenectomy group. The mean platelet count at presentation was 9,000/cumm. The mean age was 8.9 years and 13.0 years and the male to female ratio was 1:1 and 1:1.2 in anti-D and splenectomy group respectively. 54.5% of the patient in the anti-D group responded compared to 81.8% in the splenectomy group. Median time to achieve a response was 7 days in the anti-D group and 1 day in the splenectomy group. Mean time to relapse was 87.8 days in the anti-D group and 55.4 days in the splenectomy group. No adverse events were recorded for any of the infusions of anti-D and none of the patients had more than 0.5 gm/dl fall in the hemoglobin level following anti-D infusion. CONCLUSION: It was thus concluded that Anti-D is a relatively safe, convenient and effective therapy for chronic ITP and can be used as a splenectomy sparing agent when treatment is clinically indicated.

Adolescent↗

Lack of benefit of granulocyte macrophage or granulocyte colony stimulating factor in patients with febrile neutropenia.

OBJECTIVES: To compare the clinical benefits of granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) plus standard supportive care to supportive care alone among cancer patients with febrile neutropenia. METHODS: Clinical data were collected retrospectively from 148 consecutive cancer patients with neutropenia and fever. Patients had hematologic (i.e., acute leukemias or lymphoproliferative disorders) or non-hematologic malignancies (i.e., solid tumors including carcinoma of breast, lung, or colon). Clinical variables analyzed included: age and sex; underlying malignancies; chemotherapy regimens; symptoms at time of presentation; duration of fever prior to study enrollment; days from chemotherapy until administration of GM-CSF or G-CSF; number of previous neutropenic episodes; duration of fever and day of defervescence; absolute neutrophil count on day of defervescence; duration of neutropenia; number and types of antibiotics used; day amphotericin B begun; number of culture-documented infective episodes involving bloodstream, lung, pleura, urinary tract, gastrointestinal tract, intravenous cannulae, or skin; types of antimicrobial isolates; cost of cytokine therapy; length of hospital stay and clinical outcome. RESULTS: The use of myeloid growth factors increased the number of circulating peripheral white blood cells, but no significant effect was noted in terms of duration of neutropenia or fever, number of culture-proven infections (except pneumonia; p < 0.04), length of hospital stay, or survival. CONCLUSION: In areas with limited health care resources, expensive treatment with GM-CSF or G-CSF should be reserved for patients with complicated febrile neutropenia where the expected risk of infection is high and the duration of neutropenia is prolonged, or those with documented infections that are refractory to antibiotic treatment.

Adult↗

Cancer patterns in Karachi division (1998-1999).

OBJECTIVE: A minimal cancer incidence data for Karachi, the largest city of Pakistan, is being presented here, for the years 1998-1999. The city has a population of 9,802,134; males 5,261,712 (52.6%) and females 4,540,422 (47.4%); census 1998. METHODOLOGY: A predominantly mixed (passive and active) registration system has evolved in Karachi, the data sources being the hospitals within the Karachi Division. The reported/retrieved cancer data sets at the Karachi Cancer Registry are checked, coded, computerised in an analytical format and analysed. RESULTS: The incident cancer cases registered in Karachi, during the 2-year period, 1st January 1998 to 31st December 1999 were analysed. The age-standardised incidence rate (ASR) of cancer, all sites was 132.4/100,000 for the males. Cancer of the lung 10.8%; ASR 17.3 was the most frequently recorded malignancy, followed by oral cavity 10.5%; ASR 13.2 and larynx 5.0%; ASR 7.4. The age-standardised incidence rate (ASR) of cancer, all sites was 133.0/100,000 in the females. Cancer of the breast, 32.0%; ASR 40.7 was the most frequently recorded malignancy, followed by oral cavity 8.1%; ASR 11.7 and gall bladder 3.6%; ASR 5.5. CONCLUSION: The present data has been calculated with an estimated 15-20% probable under ascertainment. Tobacco-associated cancers in Karachi were responsible for 38.3% of the tumours diagnosed amongst the males. Two principal cancers, breast and oral cavity were responsible for 40.1% of the cancers in females. A rare finding was the high incidence of gall bladder cancer in the females. At present it is difficult to determine whether this indicates a genuine high risk or a selection bias. A continuous process of cancer registration to study the trends in the incidence and an adequate cancer control program are possible and essential for Pakistan and can be based on the pattern being practiced in Karachi.

Breast Neoplasms↗

Acute myeloid leukemia in children in Pakistan: an audit.

OBJECTIVE: To see the clinical features and treatment of children with Acute Myeloid Leukemia (AML) in Pakistan. SETTING: Tertiary referral at a specialist Hematology/Oncology center. METHODS: Retrospective, chart-based review of children (less than 14 years) admitted to the hospital with a diagnosis of AML between January 1987 and August 1997. RESULTS: A total of 23 patients were admitted. There were 18 males and 5 females. The mean age was 8 +/- 5 years. M3 was the commonest morphological subtype (43%). Twenty-two percent of the patients presented with hyperleucocytosis (TLC > 100 x 10(9)/L) and 95% with an elevated LDH (> 548 IU/L). Pneumonia at presentation was seen in 29%. Of 23 patients 14 were evaluable for responses. Six patients died early (43%); 3 before starting the chemotherapy and 3 during the induction chemotherapy, 8/11 (73%) patients entered remission. The median survival was 9 months. CONCLUSION: The pediatric patients with acute myeloid leukemia present with advanced disease. There is a high early death rate (within 28 days of diagnosis). The long-term outcome was inferior to that reported in the literature.

Acute Disease↗

Long-term outcomes of acute myeloid leukemia in adults in Pakistan.

OBJECTIVE: To describe the long-term outcomes of Acute Myeloid Leukemia (AML) and to study clinicopathological features at presentation, morphological subtypes and remission rates. METHODS: Demographic information, response to therapy and survival of patients (>14 years of age) admitted between January 1988 to August 1996 with acute myeloid leukaemia was retrieved and analysed. RESULTS: Seventy-four patients were admitted with a diagnosis of AML during the study period. There were 43 males and 31 females. Age ranged between 15 and 70 years with a mean age of 38 years. The most common presenting feature was fever (67.5%) and the morphological subtype according to French-American-British Group (FAB) criteria was M4. Fifty-five patients received treatment and were evaluable for response and outcomes. Thirty-six (65.4%) patients had complete remission. Sixteen (29.1%) died during the first 28 days after starting induction chemotherapy. The median survival was 11 months. Six (11%) patients (4 females, 2 males) are surviving beyond 4 years (long-term survivors). CONCLUSION: Our study suggests that the long-term outcomes of adults with AML are comparable to what has been reported in the literature for patients who do not receive bone marrow transplants.

Adolescent↗

Flow cytometric analysis of childhood leukemias.

OBJECTIVE: To collect demographic data for childhood (less than 15 years) leukemias in Karachi, describe the accuracy of the cell surface markers routinely used in the flow cytometric analysis of leukemic cells and arrive at an ideal panel of antibodies for analyzing leukemic samples. MATERIALS AND METHODS: Data from 62 consecutive cases of childhood leukemias referred to the Department of Pathology, Aga Khan University Hospital, (AKUH) between January 1995 and December 1998 was analyzed using Epi Info Version 6. Flow cytometry on all samples was performed using standard protocols. RESULTS: The mean age of patients was 8.2 years and 49 (79%) were males. Fifty (81%) had acute lymphoblastic leukemias of which 50% were CD10 positive and 24% CD10 negative Pre-B cell leukemias. Among all Pre B cell All 98% were positive for CD19, 96% for CD22, 89% for HLA-DR and 67% for CD10. Of the 10 AML cases, 100% were positive for CD33, 90% for CD13, 80% for CD19 and 70% for HLA-DR. CONCLUSION: The mean age in this study population was significantly higher and percentage of CD10 positive Pre-B All is lower than that in the West. Both these factors might be responsible for the poorer prognosis of these patients. It is not possible to specify a minimum or maximum panel of antibodies that should be used for phenotyping all cases of childhood leukemias. A certain degree or redundancy is essential in any panel of antibodies used for flow cytometry of leukemias.

Acute Disease↗