It is well known that diagnostic accuracy of the clinical cause of death has not improved despite advances in diagnostic techniques. We aimed to investigate the accuracy of the clinical cause of death compared with the autopsy cause of death and to see if the Coroner's autopsy can play a role in clinical audit. Our study population consisted of all autopsies where the deceased was hospitalised or resuscitated at the Accident and Emergency Unit of the University of Malaya Medical Centre before death, performed during the period July 1998 to June 2000. The cases were subdivided according to natural and unnatural causes of deaths. Natural deaths were further subdivided in relation to the main organ systems involved while unnatural deaths were subcategorised into trauma, poisoning and burns. The rate of agreement between clinical and autopsy cause of death was further compared with duration of survival in the hospital. Of 132 autopsies included in this study, 115 were Coroner's autopsies. 78% of cases showed agreement between clinical and autopsy cause of death. The agreement rate in Coroner's cases was 80.0%. For natural and unnatural causes, the agreement rate was 56.7% and 84.3% respectively. There were 6 cases (4.5%) where an initial accurate diagnosis might have altered the prognosis of the deceased. In general, the rate of agreement increased with duration of survival of patients. However, this was no longer observed after a survival of more than 28 days. Our findings agree with other similar studies. The diagnostic accuracy of cause of death has not improved despite the modernisation in medical technology. The autopsy still plays an important role in clinical audit and medical education.
The increasing prevalence of penicillin-resistant Streptococuus pneumoniae urges for fast and accurate susceptibility testing methods. This study evaluated the comparability of three commonly used techniques; disk diffusion, E-test and agar dilution, to detect penicillin susceptibility in clinical isolates of S. pneumoniae. Fifty pneumococcal isolates, obtained from patients at the University of Malaya Medical Centre, were selected to include both penicillin-susceptible strains and those that had decreased susceptibility (resistant and intermediate) to penicillin. The minimum inhibitory concentration (MIC) values of penicillin to serve as the reference was determined by the agar dilution method in which, based on the MIC breakpoints recommended by the National Committee for Clinical Laboratory Standards (NCCLS), 27 strains had decreased susceptibility to penicillin with 17 strains resistant and 10 intermediate. Comparing to the agar dilution method, oxacillin disk diffusion test detected all strains with decreased penicillin susceptibility as such while E-test showed a close agreement of susceptibility (92%) of the isolates to penicillin. This confirmed that oxacillin is a good screening test for S. pneumoniae isolates with decreased susceptibility to penicillin while E-test is very reliable for rapid and accurate detection of penicillin susceptibility.
A 2-year-old boy with underlying congenital cyanotic heart disease presented with seizures and fever and was found to have bilateral parietal cerebral abscesses. Drainage of the pus from the abscesses was done in stages; on the day of admission, four days after admission and 3 weeks after admission. Although the pus from the first drainage did not grow any organisms, the pus from the second drainage on the fourth day of admission yielded a mixed growth of Eikenella corrodens and Streptococcus milleri. Following the second drainage of pus, the child was noted to have mild weakness (grade 3/5) and increased tone in the left upper limb. Three weeks after admission, due to recurring fever, further neurological signs and findings of an enlarging right cerebral abscess on a repeat CT scan, a third drainage was carried out. However no growth was obtained from this specimen. This patient was managed both surgically and with appropriate antibiotics. Over the next four months, serial CT scans revealed gradual resolution of the abscesses with disappearance of the surrounding oedema. The child showed gradual recovery of his left sided weakness with resolution of tone and reflexes to normal.
Event reporting can provide data to study the failure points of an organization's work process. As part of the ongoing efforts to improve transfusion safety, a Medical Event Reporting System Transfusion Medicine, (MERS - TM) as designed by Kaplan et al was implemented in the Transfusion Medicine Unit of the University Malaya Medical Centre to provide a standardized means of organized data collection and analysis of transfusion errors, adverse events and near misses. An event reporting form was designed to detect, identify, classify and study the frequency and pattern of events occurring in the unit. Events detected were classified according to Eihdhoven Classification model (ECM) adopted for MERS - TM. Since our system reported all events, we called it Event Reporting System - Transfusion Medicine (ERS-TM). Data was collected and analyzed from the reporting forms for a period of five months from January 15th to June 15th 2002. The initial half of the period was a process of evaluation during which 118 events were reported, coded, analyzed and corrective measures adopted to prevent the recurrence of the same event. The latter half saw the reporting of 122 events following the adoption of corrective measures. There was a reduction in the occurrence of some events and an increase in others, which were mainly beyond the organization's control. A longer period of evaluation is necessary to identify the underlying contributory causes that can be useful to develop plans for corrective and preventive action and thereby reduce the rate of recurrence of errors through proper training and adoption of just culture.
Rearrangement of the immunoglobulin heavy chain (IgH) gene has been used as a marker of lineage and clonality in the diagnosis of B lymphoproliferative disorders. A number of PCR-based techniques have been developed to overcome the disadvantages of Southern blotting, the standard technique in detecting IgH gene rearrangement. Using an established seminested PCR technique with consensus primers to the V and J regions of the IgH gene, we analysed DNA prepared from peripheral blood and/or bone marrow specimens from 30 cases of known B cell malignancies (16 chronic lymphocytic leukemia, 11 acute lymphoblastic leukemia and 3 Non-Hodgkin Lymphoma), 3 cases of T lymphoproliferative disease and 3 cases of reactive lymphocytosis diagnosed in Hospital UKM to detect rearranged IgH gene. We found that monoclonality as represented by the presence of rearranged IgH gene were demonstrated in all the 30 cases. The PCR findings showed 100% concordance with the Southern blot analysis results which also showed rearranged IgH bands in all the 30 cases. We also found that none of the cases of T lymphoproliferative diseases and reactive lymphocytosis showed presence of rearranged IgH band, suggesting that the amplification using the IgH primers is lineage-specific. In conclusion, we find the PCR a useful method to detect IgH gene rearrangement in peripheral blood and bone marrow specimen. Since the PCR results are comparable to that of the Southern blotting in demonstrating B cell monoclonality and owing to its many advantages we feel that it can replace the Southern blot technique for the diagnosis of B cell malignancies.
A 26-year-old Indian lady was admitted for lower abdominal pain, diarrhoea, vomiting, fever and cough. The initial diagnosis was that of peritonitis secondary to ruptured or perforated viscus with lobar pneumonia. On laparotomy, she was found to have necrotizing or Kikuchi's lymphadenitis of the abdominal lymph nodes. The initial two antinuclear antibody (ANA) results came back negative. She was diagnosed to have systemic lupus erythematosus (SLE) when the third sample for ANA came back positive and the double-stranded DNA (dsDNA) antibody test was homogenously positive. This case illustrates a need to be aware that necrotizing lymphadenitis can precede the onset of systemic lupus erythematosus.
Lymphoma is a relatively common group of neoplasms diagnosed in hospital practice. This study aims to elucidate the pattern of this disease encountered in a public service hospital of the Ministry of Health, Malaysia.
This study investigated the effects of a tocotrienol-rich fraction (TTRF) on the microscopic development of atherosclerosis and lipid peroxidation in the aorta of rabbits. Group 1 was fed a normal diet, group 2 received a 2% cholesterol diet and group 3 received a 2% cholesterol diet plus daily oral administration of the TTRF. After 10 weeks, the aortic content of malondialdehyde (MDA) was measured as an index of lipid peroxidation. The MDA was lowest in rabbits that received the TTRF compared to the groups that did not. The degree of intimal thickening was higher in the cholesterol-fed rabbits without the TTRF compared to the cholesterol-fed rabbits with TTRF (P<0.05). The continuity of the internal elastic lamina (IEL) was noted to be preserved in the cholesterol-fed rabbits with TTRF but appeared disrupted in the cholesterol-fed rabbits without the TTRF. The disrupted and fragmented IEL may have resulted from the injury caused by lipid peroxidation that contributed to the more extensive intimal thickening. We conclude that the antioxidant activities of the TTRF can reduce experimental atherosclerosis.
p53 is the most commonly mutated gene in human cancers. It encodes a 53 kilodalton protein with several evolutionarily conserved domains viz sequence-specific DNA binding, tetramerisation, SH3 molecule binding, C-terminal and N-terminal. Existing in the cell at a very low level and in a relatively inactive form, p53 protein is increased and activated during periods of cellular stress. Unlike other proteins, the increase in protein level and its activation result from modification of the protein rather than genetic transcriptional or translational upregulation. Normally, Mdm2 protein interacts with p53 protein and effectively targets it for ubiquitin proteolysis within an autoregulatory feedback loop. Phosphorylation at the N-terminus reduces p53 interaction with Mdm2 with a resultant increase in p53 protein level. Modification at the C and N termini via phosphorylation or acetylation upregulates binding to specific DNA targets increasing transcription of these downstream genes. The net effect of p53 protein increase and activation lies in arrest of the cell in cycle which allows time for repair of the incurred damage or apoptosis or death of the cell. Failure of these normal protective and adaptive mechanisms caused by mutation of the p53 gene with product of an abnormal protein, loss of p53 protein through interaction with and degradation by HPV E6 protein or overexpressed Mdm2 etc. permits DNA-damaged cells to continue replicating. Left unchecked, this frequently contributes to tumourigenesis. Various methods have been devised to screen for mutations of the p53 gene, still the most common source of failed p53 mechanism. These include immunohistochemical detection of mutated proteins or identification of altered electrophoretic mobility of mutated p53 sequences. Sequencing of the gene nonetheless remains the most accurate method for determination of mutation. Major advances have been made in p53 research but the most meaningful probably lies in the promising results achieved in tumour therapy where introduction of wild type p53 gene has resulted in regression of non-small-cell lung cancer (NSCLC). Many other notable developments in this field include description of p53 homologues, "gain of function" mutants, p53 polymorphisms, angiogenesis-inhibiting properties of wild type p53 protein etc.
The application of modern research tools has broadened our understanding of the chlamydiae and their role in disease. Chlamydial genome analysis showed the presence of genes for ATP and peptidoglycan synthesis, contradicting the common belief that chlamydiae lack the ability to produce these compounds. Phylogenetic tree analysis suggests that chlamydiae could have evolved from an intracellular existence in amoebae. Newly discovered obligate intracellular organisms with chlamydia-like life-cycles have been classified as chlamydiae by rRNA homology with existing chlamydial species. A proposed new classification adds three new families to the order Chlamydiales as well as creates two genera and nine species within the family Chlamydiaceae. Chlamydiae are incriminated in an increasingly large spectrum of diseases both in humans and in animals. The emergence of multi-drug resistant C. trachomatis strains forewarns therapeutic problems with this organism. While C. pneumoniae remains a significant respiratory pathogen, the role it plays in the pathogenesis of atherosclerosis and ischaemic heart disease awaits definition.
An eight-week-old infant presented with dyspnoea two months after an uneventful normal vaginal delivery. Radiologically, a sharply outlined radiolucent area surrounded by atelectasis was seen in the upper lobe of the left lung. A left upper lobectomy was performed with the clinical impression of congenital pulmonary emphysema. The resected specimen displayed multiple cysts 2 to 6 mm in diameter. Microscopically, intracystic papillary mesenchymal ingrowths lined by respiratory epithelium were present. Based on both the gross and microscopical features, a diagnosis of Fisher's variant of type II congenital cystic adenomatoid malformation (CAM) was made. The postoperative follow-up showed excellent recovery and normal development of the child.
Medico-legal problems experienced by histopathologists differ from those of other clinicians as they are rarely in direct contact with patients. Nevertheless, the pathologist owes a duty of care to the patient and is liable for medical negligence. In the absence of local guidelines, it is prudent to follow guidelines published by learned Colleges elsewhere. This is also true when delegating duties to non-pathologists, technical and other support staff. Errors in diagnosis and documentation pose the most common problems in histopathology. In this, liability also depends on many factors including the provision of adequate clinical information by clinicians and competence of laboratory staff. Clinicopathological discussions, participation in quality assurance programmes and adherence to standard operating procedures are important audit activities to minimize and detect errors as well as prevent grievous outcome to patients. Issues also arise over the retention of specimens and reports. In general, wet, formalin-fixed tissues should be kept until histopathological assessment is finalized and preferably after clinicopathological sessions, and even longer if there is potential litigation. Reports should be archival. Paraffin blocks should be kept for at least the lifetime of the patient, and histology slides for at least 10 years, to facilitate review and reassessment. Despite adverse publicity in the foreign press over the use of human organs and tissues for research and education, it is accepted that processed tissues can be used for research and educational purposes provided the patient's identity is kept confidential. Nevertheless, it would be prudent to revise consent forms for surgery and autopsies to include the possibility that tissues removed can be stored or used for research and education. Good medical practice in pathology encourages a willingness to consult colleagues when in doubt, but advises that the treating clinician be informed if histopathological material is referred away for a second opinion. The Telemedicine Act of Malaysia (1997) requires practitioners outside Malaysia providing diagnosis through telepathology to hold a certificate to practice telemedicine issued by the Malaysian Medical Council. It is likely that the medico-legal scene in histopathology will change in the coming years with the advent of other new ancillary investigative techniques.
This is a prospective study on accidents occurring in the Pathology laboratories of Hospital Ipoh over the 3-year period from January 1996 to October 1999. 15 mishaps were recorded. The location of the accidents were the histology (40%), microbiology (33%), haematology (20%) and cytology (7%) laboratories. No mishaps were reported from the clinical chemistry, blood bank and outpatient laboratories. Cuts by sharp objects were the most common injuries sustained (47%) followed by splashes and squirts by fluid such as blood or chemicals (27%). There was 1 case each of contact with biohazardous fluid, burn, allergy and accidental drinking of disinfectant. 67% of the accidents involved medical laboratory technicians, 20% involved attendants and the rest were medical officers and the junior laboratory technicians. Although the accidents reported appeared trivial, it is vital to document them and bring them to the attention of all concerned in the laboratory, in order to prevent major accidents and also because of medico-legal implications. The role of the Laboratory Safety Committee cannot be overemphasised. Modification of staff attitude is considered an important remedial goal.
In late 1998, a novel paramyxovirus named Nipah virus, emerged in Malaysia, causing fatal disease in domestic pigs and humans with substantial economic loss to the local pig industry. Pteropid fruitbats have since been identified as a natural reservoir host. Over the last two decades, the forest habitat of these bats in Southeast Asia has been substantially reduced by deforestation for pulpwood and industrial plantation. In 1997/1998, slash-and-burn deforestation resulted in the formation of a severe haze that blanketed much of Southeast Asia in the months directly preceding the Nipah virus disease outbreak. This was exacerbated by a drought driven by the severe 1997-1998 El Niño Southern Oscillation (ENSO) event. We present data suggesting that this series of events led to a reduction in the availability of flowering and fruiting forest trees for foraging by fruitbats and culminated in unprecedented encroachment of fruitbats into cultivated fruit orchards in 1997/1998. These anthropogenic events, coupled with the location of piggeries in orchards and the design of pigsties allowed transmission of a novel paramyxovirus from its reservoir host to the domestic pig and ultimately to the human population.
A 21-year-old lady was admitted with a one year history of painless swelling in the neck. The clinical features and radiological findings suggested a thyroglossal duct cyst. Histology of the excised duct cyst showed papillary carcinoma. Ultrasound examination of the thyroid gland was normal. The patient is on regular follow-up and is well two years following surgery.
The purpose of this study is to determine the efficiency of blood utilization for elective surgery at the University of Malaya Medical Centre (UMMC). A similar study conducted six years earlier in the same unit resulted in the introduction and implementation in December 1997 of the local Maximum Surgical Blood Order Schedule (MSBOS) and the Group Screen and Hold (GSH) procedure instead of a full crossmatch. This paper compares the findings of the current study with that conducted earlier.
Mucinous carcinoma of the lung, also known as colloid carcinoma, is an uncommon tumour that is rarely encountered in fine needle aspiration (FNA) cytological practice. A 64-year-old Chinese male presenting with blood stained sputum and hoarseness of voice was discovered to have a 3 cm sized mass in the left lung. Neither bronchial washings nor transthoracic FNA yielded positive results at this stage. Six months later the patient returned to the hospital with a larger tumour and mediastinal lymphadenopathy. Transbronchial lymph node FNA, reported as negative for malignancy showed normal, hyperplastic and mildly atypical bronchial epithelial cells as well as a few single cells and extracellular mucin. Transthoracic FNA of the lung lesion performed under computed tomographic guidance showed characteristic cytological features of this tumour, establishing the diagnosis.
Malignant melanoma involving the gastrointestinal tract is diagnosed antemortem in only a small percentage of patients with the disease. Presenting symptoms are often non-specific, causing a diagnostic problem. The vast majority of such melanomas are metastatic from a cutaneous primary, however there is evidence that the tumour can arise de novo in the gastrointestinal system. We report a 74-year-old man with malignant melanoma with an unusual presentation simulating a symptomatic gastric ulcer. He presented with epigastric pain, haematemesis and melaena. Explorative laparotomy revealed a large ulcerated tumour with several pigmented satellite nodules in the proximal stomach, multiple ileal nodules and widespread nodal and liver metastases. Proximal gastrectomy and limited small bowel resection was performed. Histology revealed the tumour to be composed of nests of epithelioid cells with melanin pigment. The tumour cells showed immunohistochemical positivity for S100 protein and HMB45 antibodies. This report emphasizes that melanoma should be a diagnostic consideration in patients with gastric ulcer.
An in-house prepared M. furfur antigen was used to carry out a seroprevalence study in an urban population in Malaysia by indirect immunofluorescence assay. Of the 800 serum samples from all ages screened, 738 samples were positive for M. furfur specific IgG, giving an overall seropositive rate of 92.3%. There was no significant difference in the seropositive rates among the different gender group and races. However, there was a statistical significant difference in the seropositive rate among different age groups with a lower rate (73%) for the age group 5 years old and below, which increased rapidly to 99% for the 16 to 20 years old age group but declined slightly for the oldest age group. The degree of seropositivity, which semi-quantitatively reflect the anti-M. furfur specific IgG titre, did not show any significant difference among the gender and racial groups. On the other hand, there was a significant difference in the degree of seropositivity among the various age groups, with the 16 to 20 years old age group having the highest antibody titre and the extreme of age groups having the lower antibody titre.