Topic Update

Volume 4, Issue 1, April 2009

TAI, Morris

Associate Consultant, Department of Pathology and Clinical Biochemistry, Queen Mary Hospital

Introduction

The prevalence of diabetes mellitus (DM) has been increasing in recent years and DM is now a global epidemic. Haemoglobin A1c (HbA1c) plays an important role in the management of DM as the vast majority of outcome  studies on diabetic complications are based on it. The most famous of such studies, which demonstrated the relationship of HbA1c to diabetic complications, are the Diabetes Control and Complications Trial (DCCT) & the United Kingdom Prospective Diabetes Study (UKPDS). HbA1c is formed via a posttranslational nonenzymatic attachment of glucose to haemoglobin in an irreversible fashion. In strict chemical terms, the molecular structure of HbA1c is β-N-(1-deoxy)-fructosyl-haemoglobin and it serves as an indicator of glycaemic control over the preceding 2- to 3- month period.

There are a great number of analytical methods used in the measurement of HbA1c. More than 20 methods were in clinical use as reported in the year 2004. The heterogeneity of methodology eventually generated concerns about comparability and usability of HbA1c, especially when patients’ data were to be compared with study results. The call for test standardization was therefore critical. Various standardization programmes have been carried out since the 1990s. The National Glycohaemoglobin Standardization Program (NGSP) and the International Federation of Clinical Chemistry (IFCC) are the two mostimportant international standardization programmes while local ones such as Japan Diabetes Society/Japanese Society for Clinical Chemistry (JDS/JSCC) and Mono-S have been adopted in Japan and Sweden respectively.

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Volume 3, Issue 3, December 2008

IP, Margaret

Professor, Department of Microbiology, The Chinese University of Hong Kong

Introduction - Global Concerns and Challenges

Throughout the world, healthcare professionals are concerned at the growing problem of antimicrobial resistance and the global emergence of multi-drug-resistant organisms (MDROs) in the health care setting and in the community. The use of penicillin in early 1940s on a wider scale, and the subsequent newly-introduced antimicrobials, was soon followed by the emergence of resistantmicrobes. Some of the seresistant organisms in relation to the introduction of antimicrobial agents are listed in Table 1. The prevalence of MDROs has increased dramatically worldwide during the last decades [1]. Most alarmingly are in infections caused by MDROs whereby resistance has developed for virtually all currently available drugs and no effective therapies are available. This is compromised by the lack of new discovery of potent classes of antimicrobials in recent time, with shortfalls in funding for the development of new drugs which often relies on interests andsupport from pharmaceutical industries.

In a wider context, this threat to treatment and control of infectious diseases ranges beyond that of common bacterial pathogens. Drug resistance to infectious agents causing tuberculosis, malaria, pandemics of HIV, and in fluenza including H5N1, is also increasingly recognized, affecting treatment and hampering their containment. Antimicrobial resistance makes infections more difficult to treat; prolongs duration and increases severity of illness. This lengthens the period of infectivity, enhances spread and poses the added challenge to infection control. In effect, this translates to increases in direct and indirect health care costs and a higher morbidity and mortality.

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Volume 3, Issue 2, August 2008

KWOK, SY Janette

Associate Consultant, Division of Transplantation and Immunogenetics, Department of Pathology and Clinical Biochemistry, Queen Mary Hospital, Hong Kong

Introduction

Immunogenetics is the study of the immune response in relation to genetic makeup. The immune system protects the vertebrates from all potential harmful infectious agents such as bacteria, virus, fungi and parasites. The growing understanding of the immune system has influenced diversified biomedical disciplines, and is playing a significant role in the study and treatment of many diseases such as cancer and autoimmune conditions.

The launch of immunogenetics could be traced back to the demonstration of Mendelian inheritance of the human ABO blood grouping in 1910. Major developments leading to the emergence of immunogenetics were accounted by the rediscovery of allograft reactions during the Second World War and the formulation of the immunological theory of a llograft reaction and the clonal selection hypothesis by Burnett in 1959.

The field of immunogenetics has exploded during the last 25 years, thus expanding the range of concepts with the potential to improve the field of medicine with regard to transplantation, immunotherapy and the study of immune polymorphisms. Immunogenetics has poised on the brink of a new era, driven by the development of new technologies and shaped by fundamental discoveries about the mech anisms that regulate interactions between the adaptive and innate immune systems. Technologies are developed to revolutionize genetic analysis and providing new strategies for elucidating the genetic mechanisms that influence immune responsiveness and autoimmunity.

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Volume 3, Issue 1, April 2008

BEH, SL Philip 

Associate Professor (Forensic Pathology), Department of Pathology, Li Ka Shing Faculty of Medicine The University of Hong Kong

The autopsyinterview is an anomaly which arose in Hong Kong at a time when the Coroner did not speak the local language and the police officer investigating the death had very little medical knowledge. The hospital anatomical pathologists and forensic pathologists were therefore delegated the task of obtaining medical information from the Cantonese speaking next-of-kin which may be related to the death and providing a written English summary for the Coroner. The legal authority on the decision to autopsy or to waive an autopsy had always rested with the Coroner. However, the practical decisions were effectively made by the pathologists based on the available me dical information or the lack of information. 

In the context of this background, the autopsy interview developed in Hong Kong. It was a relatively easy exercise for the pathologist. The next-of-kin of the deceased attended interviews with the pathologist in the presence of a police officer. The pathologist asked for medical history and details of the circumstances of the death. The next-of-kin in the 70’s and 80’s were told an autopsy was to be performed as it was a legal requirement. In the rare circum stances where a request was made to waive the autopsy, the pathologist had to be convinced of the existence of a probable cause of death. Where none was evident, the application for waiver was denied and the opportunity to make the written waiver application denied too. The autopsy was again duly ordered by the Coroner on the basis that if the pathologist was unable to provide a cause of death, the cause of death was unknown and had to be established.

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Volume 2, Issue 2, July 2007

Dr. CHEUK Wah

BSc(Hons), MBBS, FHKCPath, FRCPA, Associate Consultant, Department of Pathology, Queen Elizabeth Hospital 

Overview of conventional molecular techniques in lymphomas

The use of molecular techniques in hematolymphoid pathology started with cloning of the immunoglobulin and T cell receptor genes. [1] This is followed by the cloning of a number of translocation breakpoints in some common lymphoma types.[2-4] Assay of chromosomal breakpoints not only helps in confirming a clonal proliferation but also prov ides an indication of the type of lymphoma. The main application is to establish clonality or lineage of a lymphoid proliferation. 

Southern blot analysis was the standard technique in molecular studies. The advent of the polymerase chain reaction (PCR) provides an alternative technical approach to Southern blot analysis, allowing molecular studies to be performed in many diagnostic laboratories. PCR technique is technically simpler, has a much faster turnaround time, requires a much smaller quantity of clinical materials, and can be performed on archival, formalin-fixed, paraffin-embedded samples (Figure 1).[5] Advances in PCR techniques allow accurate quantitation of the template (real time PCR) and make it possible to use RNA as the starting material (revers transcriptase PCR).[6] Fluorescence in situ hybridization (FISH) utilizes oligonucleotide probes to localize specific chromosomal segment so that translocation can be visualized under the fluorescence microscope.[7] This “interphase cytogenetics” technique obvi ates the need of fresh specimen and cell culture and revolutionizes the traditional cytogenetics.[8] Although FISH may not be as sensitive as PCR-based methods, it is superior in detecting complex karyotypic abnormalities involving multiple fusion partners and has lower false negative rates in detection of chromosomal translocations in some lymphoma types.

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