Kaiser Ali

University of Toronto, Toronto, Ontario, Canada

Are you Kaiser Ali?

Claim your profile

Publications (28)

  • Source
    Full-text Dataset · Sep 2013
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Inherited bone marrow failure syndromes (IBMFSs) often have substantial phenotypic overlap, thus genotyping is often critical for establishing a diagnosis. To determine the genetic characteristics and mutation profiles of IBMFSs, a comprehensive population-based study that prospectively enrols all typical and atypical cases without bias is required. The Canadian Inherited Marrow Failure Study is such a study, and was used to extract clinical and genetic information for patients enrolled up to May 2010. Among the 259 primary patients with IBMFS enrolled in the study, the most prevalent categories were Diamond-Blackfan anaemia (44 patients), Fanconi anaemia (39) and Shwachman-Diamond syndrome (35). The estimated incidence of the primary IBMFSs was 64.5 per 10(6) births, with Fanconi anaemia having the highest incidence (11.4 cases per 10(6) births). A large number of patients (70) had haematological and non-haematological features that did not fulfil the diagnostic criteria of any specific IBMFS category. Disease-causing mutations were identified in 53.5% of the 142 patients tested, and in 16 different genes. Ten novel mutations in SBDS, RPL5, FANCA, FANCG, MPL and G6PT were identified. The most common mutations were nonsense (31 alleles) and splice site (28). Genetic heterogeneity of most IBMFSs was evident; however, the most commonly mutated gene was SBDS, followed by FANCA and RPS19. From this the largest published comprehensive cohort of IBMFSs, it can be concluded that recent advances have led to successful genotyping of about half of the patients. Establishing a genetic diagnosis is still challenging and there is a critical need to develop novel diagnostic tools.
    Full-text Article · Jun 2011 · Journal of Medical Genetics
  • Source
    S K Hashmi · C Allen · R Klaassen · [...] · Y Dror
    [Show abstract] [Hide abstract] ABSTRACT: Hashmi SK, Allen C, Klaassen R, Fernandez CV, Yanofsky R, Shereck E, Champagne J, Silva M, Lipton JH, Brossard J, Samson Y, Abish S, Steele M, Ali K, Dower N, Athale U, Jardine L, Hand JP, Beyene J, Dror Y. Comparative analysis of Shwachman-Diamond syndrome to other inherited bone marrow failure syndromes and genotype–phenotype correlation. Our knowledge of the phenotypes of inherited bone marrow failure syndromes (IBMFSs) derives from case reports or case series in which only one IBMFS was studied. However, the substantial phenotypic overlap necessitates comparative analysis between the IBMFSs. Shwachman–Diamond syndrome (SDS) is an IBMFS that the appreciation of what comprises its clinical phenotype is still evolving. In this analysis we used data on 125 patients from the Canadian Inherited Marrow Failure Study (CIMFS), which is a prospective multicenter population-based study. Thirty-four cases of SDS patients were analyzed and compared to other patients with the four most common IBMFSs on the CIMFS: Diamond Blackfan anemia, Fanconi anemia (FA), Kostmann/severe congenital neutropenia and dyskeratosis congenita (DC). The diagnosis of SDS, FA and DC was often delayed relative to symptoms onset; indicating a major need for improving tools to establish a rapid diagnosis. We identified multiple phenotypic differences between SDS and other IBMFSs, including several novel differences. SBDS biallelic mutations were less frequent than in previous reports (81%). Importantly, compared to patients with biallelic mutations, patients with wild type SBDS had more severe hematological disease but milder pancreatic disease. In conclusion, comprehensive study of the IBMFSs can provide useful comparative data between the disorders. SBDS-negative SDS patients may have more severe hematological failure and milder pancreatic disease.
    Full-text Article · May 2011 · Clinical Genetics
  • Kaiser Ali · Todd Reichert · Daniel Gomez · [...] · Colleen Christensen
    [Show abstract] [Hide abstract] ABSTRACT: Mid-infrared spectromicroscopy studies on biological tissue sections require accurate identification of tumor-bearing areas in histology-stained and infrared-unstained tissue sections. Concordance was achieved as follows: paired stained and unstained thin (5 microm) human brain tumor cryosections mounted on slides were scanned with a Nikon Coolscan 4000 film scanner at 4000 dpi, edited with Adobe Photoshop CS2 software, and both digital images saved. A digital tractile grid, developed in our laboratory, was overlaid onto both images. Boundaries of tumor-containing areas in stained sections were identified by light microscopy, and a digital boundary map constructed. The map was transferred onto the unstained spectromicroscopy tissue image, and finally layered onto the gridded, equisized, spectromicroscope-generated overview image prior to Fourier transform infrared spectromicroscopy. Accurate identification of tumor-bearing areas, normal brain tissue and transitional zones allowed for meaningful interpretation of respective spectral patterns in detecting subtle differences within biochemical profiles. This is the first reported method of a standardized technique for ensuring concordance in mapping of malignant tumors by mid-infrared spectromicroscopy. This technique is applicable to all biological thin tissue sections, and serves to enhance accuracy of concordance between globar- and synchrotron-light generated infrared data with that obtained by conventional light microscopy.
    Article · Oct 2010 · Oncology Reports
  • Kaiser Ali · Yanjie Lu · Umashankar Das · [...] · Eric Pellerin
    [Show abstract] [Hide abstract] ABSTRACT: Glioblastoma multiforme (GBM) is one of the most malignant human tumors, with a uniformly poor outcome. One obstacle in curing malignant brain tumors is the limitation of conventional light microscopy in detecting microscopic residual tumor in biopsy samples from the perimeter of the surgically resected tumor. We further refined the identification of GBM tumor tissue at the sub-cellular level, utilising the technique of Synchrotron, sourced mid-infrared (mid-IR) spectromicroscopy. Paired, thin (5 microm) cryosections of snap-frozen human GBM tumor samples removed at elective surgery were mounted on glass slides (hematoxylin and eosin-stained tissue section) and calcium fluoride (CaF2) windows (unstained tissue section for transmission spectromicroscopy), respectively. Concordance of tumor bearing areas identified in the stained section with the unstained IR tissue section was confirmed by the pathologist of the study. Compared with molecular signatures obtained from normal control brain tissue, unique spectroscopic patterns were detected in GBM tumor samples from 6 patients. The identifying features of GBM were: i) high protein-to-lipid ratios (amide I+II/CH2 symmetric stretch; amide I+II/CH2+CH3 symmetric and asymmetric stretch), and ii) considerable enhancement of the intensities of characteristic peaks at 2,957 and 2,871 cm(-1) representing CH3 asymmetric and symmetric stretch, respectively. Spectral data sets were subjected to Ward's algorithm for assignment to similar groups, and then subjected to hierarchical cluster analysis (HCA) by means of false color digital maps. False color images of 5 clusters obtained by HCA identified dominant clusters corresponding to tumor tissue. Corroboration of these findings in a larger number of GBM may allow for more precise identification of these and other types of brain tumors.
    Article · Jul 2010 · International Journal of Molecular Medicine
  • Source
    Kaiser Ali · S Sutaryo · Ignatius Purwanto · [...] · Judy Nurse
    [Show abstract] [Hide abstract] ABSTRACT: In July 2001, a 'twinning' project was undertaken between University Gadjah Mada, Indonesia, and the Saskatchewan Cancer Agency, Canada to create a computerised Pediatric Cancer Registry at Sardjito Hospital, Yogyakarta city. To analyse information from the Yogyakarta Pediatric Cancer Registry (YPCR) in order to i) determine the prevalence of pediatric cancers in Yogyakarta Special Region and, ii) compare the demographics of pediatric malignancies in the Special Region (population: 3.3 million), with those of the Saskatchewan Cancer Registry in the province of Saskatchewan (population: 1 million). In May 2001, a computer dedicated to the YPCR was installed at Sardjito Hospital. Bilingual (English/Indonesian) data capture forms were developed for data extraction from hospital health records. Data items were then entered into a data base using the Statistical Package For Social Sciences (SPSS) program. Two projects were initiated: i) a prospective study from 2000-2009 of pediatric cancer cases from the YPCR, and ii) a comparison of demographics from both Cancer Registries during the time period 1996-2003. Comparative data were obtained for age, sex, diagnoses, and referral patterns. Results were analysed using the SPSS software program. i) In the 10 year prospective study, 1,124 pediatriccancer cases were accrued in the Yogyakarta Registry, the majority being in the age group 0-5 years. Male:female: 7:1. Leukemias were the most common diagnosis, followed by retinoblastoma and neuroblastoma. The majority of patients (68%) were referred from outside the catchment area of Yogyakarta Special Region. ii) In the 8 year archival comparative analysis, the most striking contrasts were a higher proportion of children with retinoblastoma and negligible numbers of pediatric brain tumors in the Yogyakarta Registry. This is the first published report of a computerised pediatric cancer registry in Indonesia. The differences in diagnostic frequencies noted above may, in part, be due to comparisons between the population-based Saskatchewan Cancer Registry versus the hospital-based Yogyakarta Pediatric Cancer Registry. The contrasts in demographics are multifactorial, and require further investigation.
    Full-text Article · Jan 2010 · Asian Pacific journal of cancer prevention: APJCP
  • Conference Paper · Apr 2009
  • Conference Paper · Apr 2009
  • Conference Paper · Apr 2009
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Unclassified inherited bone marrow failure syndromes are a heterogeneous group of genetic disorders that represent either new syndromes or atypical clinical courses of known inherited bone marrow failure syndromes. The relative prevalence of the unclassified inherited bone marrow failure syndromes and their characteristics and the clinical and economic challenges that they create have never been studied. We analyzed cases of inherited bone marrow failure syndrome in the Canadian Inherited Marrow Failure Registry that were deemed unclassifiable at study entry. From October 2001 to March 2006, 39 of the 162 patients enrolled in the Canadian Inherited Marrow Failure Registry were registered as having unclassified inherited bone marrow failure syndromes. These patients presented at a significantly older age (median: 9 months) than the patients with classified inherited bone marrow failure syndrome (median: 1 month) and had substantial variation in the clinical presentations. The hematologic phenotype, however, was similar to the classified inherited bone marrow failure syndromes and included single- or multiple-lineage cytopenia, severe aplastic anemia, myelodysplasia, and malignancy. Grouping patients according to the affected blood cell lineage(s) and to the presence of associated physical malformations was not always sufficient to characterize a condition, because affected members from several families fit into different phenotypic groups. Compared with the classified inherited bone marrow failure syndromes, the patients with unclassified inherited bone marrow failure syndromes had 3.2 more specific diagnostic tests at 4.5 times higher cost per evaluated patient to attempt to categorize their syndrome. At last follow-up, only 20% of the unclassified inherited bone marrow failure syndromes were ultimately diagnosed with a specific syndrome on the basis of the development of new clinical findings or positive genetic tests. Unclassified inherited bone marrow failure syndromes are relatively common among the inherited bone marrow failure syndromes and present a major diagnostic and therapeutic dilemma.
    Full-text Article · Aug 2008 · PEDIATRICS
  • Lara J Spagrud · Carl L von Baeyer · Kaiser Ali · [...] · Jan Mitchell
    [Show abstract] [Hide abstract] ABSTRACT: This study examined pain and distress from needles in children undergoing blood sampling as a function of adult-child interaction and type of venous access (i.e., central external venous lines, internalized ports, or peripheral access via venipuncture). Participants were 55 pediatric oncology patients, aged 3-18 years, who were undergoing routine blood work. Pain ratings were obtained using the Faces Pain Scale-Revised (FPS-R) and conversation during the procedure was audio taped for coding using the Child-Adult Medical Procedure Interaction Scale-Revised (CAMPIS-R). Children's ratings of pain using the FPS-R were similar in the port (M=2.57/10, standard deviation [SD]=3.46) and peripheral (M=2.56/10, SD=3.24) groups, despite the fact that most children with internal ports were given a topical anesthetic. Similarly, there were no differences between port and peripheral groups in rates of child coping or distress, or parent and nurse observations of child pain. As would be expected, external line access was not associated with pain or distress, even among very young children, suggesting that they appropriately understood the pain rating scale. Results of the transcribed CAMPIS-R data indicate that the influences in adult-child interaction are bidirectional. Support was found for the well-established positive relationship between child distress and adult reassurance and empathy. Implications for intervention and selection of central venous access devices are discussed.
    Article · May 2008 · Journal of pain and symptom management
  • Kaiser Ali · Yanjie Lu · Colleen Christensen · [...] · Rajendra K Sharma
    [Show abstract] [Hide abstract] ABSTRACT: Limitations of conventional light microscopy in pathological diagnosis of brain tumors include subjective bias in interpretation and discordance of nomenclature. A study using mid-infrared (IR) spectromicroscopy was undertaken to determine whether meningiomas, a group of brain tumors prone to recurrence, could be identified by the unique spectral 'fingerprints' of their chemical composition. Paired, thin (5-microm) cryosections of snap-frozen human meningioma tumor samples removed at elective surgery were mounted on glass (hematoxylin and eosin-stained tissue section) and infrared (unstained tissue section) reflectance slides, respectively. Concordance of the tumor-bearing areas identified in the stained section by a pathologist with the unstained IR tissue section was ensured using a novel digital grid and tumor-mapping system developed in our laboratory. Compared with the normal control, tumor samples from four meningioma patients revealed a marked decrease in bands associated with unsaturated fatty acids, particularly in the bands at 3010, 2920, 2850, and 1735 cm(-1). Spectral datasets were subjected to hierarchical cluster analyses (HCA) using Ward's algorithm for comparison and grouping of similar data groups, and were converted into color-coded digital maps for matching spectra with their respective clusters. False color images of 5 and 6 clusters obtained by HCA identified dominant clusters corresponding to tumor tissue. Corroboration of these findings in a larger number of meningiomas may allow for more precise identification of these and other types of brain tumors.
    Article · Apr 2008 · International Journal of Molecular Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background In boys with hemophilia, there is a risk ofhemorrhage resulting from circumcision. There has been nostandardised management in Indonesia. We report our experiencewith 4 hemophiliac boys who underwent circumcision at Dr.Sardjito General Hospital, Yogyakarta, in south-central Java.Objective To develop a safe, practical and accessible method toprevent bleeding in boys with hemophilia undergoing circumcisionin Indonesia.Methods Written informed consent was obtained from parentsrequesting the procedure. All boys had mild Hemophilia A (VIII:C level >7.8 U/ml) diagnosed at a median age of 4.4 years (range0.75–9 years). Median age at time of circumcision was 7.5 years(range 0.8–12 years).Results There were no intraoperative or post-circumcisionbleeding problem encountered in any of the patients, who weredischarged from hospital three days post-surgery. On follow upeight days and 12 days post-circumcision, they remained free ofcomplications.Conclusion Circumcision can be safely performed in boys withmild Hemophilia A following adequate pre-operative planningand prophylactic therapy. A standardised protocol for theYogyakarta Bleeding Disorders Program. evolving from thisexperience, is being planned.
    Article · May 2007 · Paediatrica Indonesiana
  • Source
    David Anderson · Kaiser Ali · Victor Blanchette · [...] · Gail Rock
    [Show abstract] [Hide abstract] ABSTRACT: Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for hematologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 18 hematologic conditions and formulate recommendations on IVIG use for each. A panel of 13 clinical experts and 1 expert in practice guideline development met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 3 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to hematologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Specific recommendations for routine use of IVIG were made for 7 conditions including acquired red cell aplasia; acquired hypogammaglobulinemia (secondary to malignancy); fetal-neonatal alloimmune thrombocytopenia; hemolytic disease of the newborn; HIV-associated thrombocytopenia; idiopathic thrombocytopenic purpura; and posttransfusion purpura. Intravenous immune globulin was not recommended for use, except under certain life-threatening circumstances, for 8 conditions including acquired hemophilia; acquired von Willebrand disease; autoimmune hemolytic anemia; autoimmune neutropenia; hemolytic transfusion reaction; hemolytic transfusion reaction associated with sickle cell disease; hemolytic uremic syndrome/thrombotic thrombocytopenic purpura; and viral-associated hemophagocytic syndrome. Intravenous immune globulin was not recommended for 2 conditions (aplastic anemia and hematopoietic stem cell transplantation) and was contraindicated for 1 condition (heparin-induced thrombocytopenia). For most hematologic conditions reviewed by the expert panel, routine use of IVIG was not recommended. Development and dissemination of evidence-based guidelines may help to facilitate appropriate use of IVIG.
    Full-text Article · Apr 2007 · Transfusion Medicine Reviews
  • Mark Belletrutti · Kaiser Ali · Dorothy Barnard · [...] · John Wu
    [Show abstract] [Hide abstract] ABSTRACT: Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10-year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP. Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2+/-4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up. The results from this study are consistent with published reports.
    Article · Mar 2007 · Journal of Pediatric Hematology/Oncology
  • Source
    J.M. Steele · L Sung · R Klaassen · [...] · Y Dror
    [Show abstract] [Hide abstract] ABSTRACT: Inherited bone marrow failure syndromes (IMFSs) are genetic disorders characterized by defective single-lineage or multi-lineage hematopoiesis. IMFS patients are at risk for severe cytopenias, development of marrow cytogenetic abnormalities (MCA), myelodysplasia (MDS), and malignancy. The rate of disease progression and proportion of patients at risk for these complications is currently unclear. We examined recently diagnosed IMFS patients to determine distribution of diagnoses, disease progression and development of significant outcomes. The CIMFR is a prospective multi-center study established in 2001 to register all IMFS patients in Canada. Analysis was restricted to patients diagnosed after November 30, 1997. Summary statistics were used to depict the study population while survival was described using the Kaplan-Meier method. 74 CIMFR patients were considered recently diagnosed. Median age at diagnosis was 2.7 years (range, birth to 40.6). Annual follow-up data were available for 53 (72%) patients. The five most prevalent diagnoses were Fanconi anemia (FA), Shwachman-Diamond syndrome (SDS), Diamond-Blackfan anemia (DBA), dyskeratosis congenita (DKC), and Kostmann's neutropenia (KS). Eighteen (24%) patients were unclassifiable. Twenty-eight (53%) follow-up patients had disease progression as indicated by new or worsening cytopenias, new marrow changes, or initiation of transfusion support and/or medical therapy. Fourteen (19%) fulfilled minimal diagnostic criteria for myelodysplasia. Eleven patients had hematopoietic stem cell transplantation (HSCT) by first follow-up. Five patients have died. Survival at 36 months is 89.8 +/- 5.7%. IMFS patients are often diagnosed at a young age. The relative distribution of diagnoses is similar to previous reviews of published cases; however, 25% of patients are currently unclassifiable. Disease progression has occurred in approximately 50% of follow-up patients. Early mortality is noted. Continued prospective observation of these patients is warranted.
    Full-text Article · Dec 2006 · Pediatric Blood & Cancer
  • Yanjie Lu · Ponniah Selvakumar · Kaiser Ali · [...] · Rajendra K Sharma
    [Show abstract] [Hide abstract] ABSTRACT: N-myristoylation is a process of covalent irreversible protein modification that promotes association of proteins with membranes. Based on our previous findings of elevated N-myristoyltransferase (NMT) activity in colonic epithelial neoplasms that appears at an early stage in colonic carcinogenesis, together with elevated NMT expression in human colorectal and gallbladder carcinomas, we investigated NMT activity and protein expression of NMT1 and NMT2 in human brain tumors and documented elevated NMT activity and higher protein expressions. For the first time, we have demonstrated that NMT has the potential to be used as a marker of human brain tumors. However, further studies with larger number of patients are required to establish its role as a complementary diagnostic tool. This finding has significant implications for further understanding of biological mechanisms involved in tumorigenesis, as well as for diagnosis and therapy of human brain tumors.
    Article · Feb 2005 · Neurochemical Research
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: High-dose factor prophylaxis, defined as the infusion of 25-40 factor (F) VIII International Units (IU) kg bodyweight (bw)(-1)> or = x 3 per week, started at age 1-2 years of life in boys with severe haemophilia A prevents the development of significant bleed-related arthropathy. However, programmes of prophylaxis are very expensive and venous access is a challenge. To ascertain patterns of prophylaxis in Canada during the period of a global shortage of recombinant FVIII concentrate a survey was conducted in 2001. The response rate was 83% and the survey identified 247 inhibitor-negative haemophilia A cases receiving prophylaxis, defined as the regular administration of FVIII at least once weekly, from 14 Canadian haemophilia treatment centres. The median age of the group identified was 13 years (range: 1-65) and 95% of cases had severe haemophilia A defined by a circulating factor level of <1%. The median FVIII infusion dose was 26 (range: 16-33) IU kg(-1); infusions were administered > or = x 3 per week in 67% of cases. High-dose factor prophylaxis was used most frequently in boys <5 years of age (23 of 28 cases, 82%) as compared with 56% (56 of 100), 66% (40 of 61) and 62% (36 of 58) of males ages 5-12, 13-18 and >18 years. Prophylaxis accounted for 50% of the annual Canadian FVIII consumption and was a major driving force in the 10% increase (=19.3 million FVIII IU) in the FVIII consumption in Canada in the 4-year period 1999-2003. Given the economic implications of increased use of prophylaxis prospective studies are warranted to better define optimal prophylaxis regimens in the haemophilia A population.
    Full-text Article · Nov 2004 · Haemophilia
  • Article · Apr 2004 · Journal of Pain
  • [Show abstract] [Hide abstract] ABSTRACT: The outcome for children with deep vein thrombosis (DVT) and pulmonary embolism (PE) is unknown. An understanding of morbidity and mortality of DVT/PE is crucial to the development of rational treatment protocols. The Canadian Childhood Thrombophilia Registry has followed 405 children aged 1 mo to 18 y with DVT/PE for a mean of 2.86 y (range, 2 wk to 6 y) to assess outcome. The all-cause mortality was 65 of 405 children (16%). Mortality directly attributable to DVT/PE occurred in nine children (2.2%), all of whom had central venous line-associated thrombosis. Morbidity was substantial, with 33 children (8.1%) having recurrent thrombosis, and 50 children (12.4%) having postphlebitic syndrome. Recurrent thrombosis and postphlebitic syndrome were more common in older children, although deaths occurred equally in all age groups. The incidence of recurrent thrombosis and postphlebitic syndrome are likely underestimated because of difficulties in diagnosis, especially in younger children. The significant mortality and morbidity found in our study supports the need for international multicenter randomized clinical trials to determine optimal prophylactic and therapeutic treatment for children with DVT/PE.
    Article · Jul 2000 · Pediatric Research