The prevalence of diabetes is increasing worldwide. The World Health Organisation has estimated that there will be around 300 million diabetics by 2025. The largest increase will occur in Asia. The prevalence of type 2 diabetes is increasing due to a combination of factors: increasing lifespan, sedentary lifestyle, excessive intake of high energy foods, increasing prevalence of overweight/obese people. The Finnish Diabetes Prevention Study Group has clearly shown that changes in the lifestyle of both overweight men and women with impaired glucose tolerance can reduce the incidence of type 2 diabetes by 58%. This finding was confirmed by the Diabetes Prevention Programme which found that lifestyle intervention in individuals with impaired fasting glucose or impaired glucose tolerance reduced the risk of developing type 2 diabetes by 58%, whereas treatment with metformin reduced the risk of type 2 diabetes by only 31%. Both acarbose and troglitazone have also been shown to reduce the progression to diabetes in individuals who are at high risk of developing type 2 diabetes. Since the cure for diabetes remains some way off our concerted efforts should be directed at prevention of diabetes in order to curb the increasing prevalence of diabetes worldwide. Lifestyle changes are more beneficial than long term drug therapy in the prevention of diabetes and should be actively promoted.
A blocking test was incorporated into the commercial IDEIA Adenovirus test (DAKO Diagnostics Ltd., Cambridgeshire, UK) to detect false positive results when faecal specimens were tested for adenovirus antigen. Immune rabbit serum raised against pooled adenovirus particles from human faecal specimens, together with the pre-immune serum, was used. Assessment of positive showed that false positives were produced under two different conditions: when results were based on visual determination instead of a cut-off value determined from photometric reading, and when absorbance values were not immediately read at the end of the test. Under the optimum condition for reading and assessment of test results (immediate reading and photometric determination), 11% of 65 adenovirus-positive samples were checked by the blocking ELISA as false positives. The rest of the specimens showed blocking of positive absorbance values by 70 to 98%. ELISA was found to be more sensitive than immune electron microscopy on samples with lower antigen concentration.
First-void urine samples collected from sexually transmitted diseases (STD) clinic patients were examined by a nested polymerase chain reaction (PCR) and a commercial enzyme immunoassay (IDEIA Chlamydia) for the diagnosis of Chlamydia trachomatis urethritis or cervicitis. The primers for the PCR amplified a target in the major outer membrane protein (MOMP) gene in C trachomatis while the IDEIA detected genus-specific chlamydial lipopolysaccharide. Discrepant results were resolved by retesting urine specimens with a second (plasmid-based) PCR and taking urethral or endocervical swab results into consideration. For 231 men (chlamydial prevalence 20.4%), the sensitivity, specificity, positive and negative predictive values were 59.6%, 99.5%, 96.6% and 90.6% for urine IDEIA, 68.1%, 99.5%, 97% and 92.4% for urethral swab IDEIA and 97.9%, 99.5%, 97.9% and 99.5% for urine PCR. The corresponding rates for 66 women (chlamydial prevalence 54.6%) were 19.4%, 100%, 100% and 50.8% for urine IDEIA, 86.1%, 96.7%, 96.9% and 85.3% for endocervical swab IDEIA and 91.7%, 93.3%, 94.3% and 90.3% for urine PCR. Hence, in a high prevalence population, the urine IDEIA was a suitable alternative to the male urethral swab IDEIA but significantly less sensitive than the endocervical swab IDEIA. The urine PCR was, however, much more sensitive than the urine IDEIA for both men and women and could replace the endocervical swab IDEIA for the diagnosis of chlamydial cervicitis.
In vitro generated cloned full length dengue 2 virus untranslated regions (UTRs) were used in RNA gel mobility shift assays to examine cellular factors binding to the virus genomes. Cellular factors in lysates of Vero (monkey) and C6/36 (mosquito) cells bound specifically and non-specifically to the dengue 2 virus 3' UTR. Non-specific interaction with the 5' UTR, resulting in formation of at least 4 band shift complexes was noted with lysate of the C6/36 cells only. Pre-treating the cell lysates with proteinase K affected binding of cellular factors to the dengue 2 virus UTRs, suggesting that the cellular factors were proteins. These findings suggest that cellular proteins could interact with specific sites on the dengue virus genomes.
Historical cottontail rabbit papillomavirus studies raised early indications of a mammalian DNA oncogenic virus. Today, molecular cloning recognises numerous animal and human papillomaviruses (HPVs) and the development of in vitro transformation assays has escalated oncological research in HPVs. Currently, their detection and typing in tissues is usually by Southern blotting, in-situ hybridization and polymerase chain reaction methods. The complete papillomavirus virion constitutes a protein coat (capsid) surrounding a circular, double-stranded DNA organised into coding and non-coding regions. 8 early (E1-E8) open reading frames (ORFs) and 2 late (L1, L2) ORFs have been identified in the coding region of all papillomaviruses. The early ORFs encode proteins which interact with the host genome to produce new viral DNA while late ORFs are activated only after viral DNA replication and encode for viral capsid proteins. All papillomaviruses are obligatory intranuclear organisms with specific tropism for keratinocytes. Three possible courses of events can follow papillomaviruses entry into cells: (1) viral DNA are maintained as intranuclear, extrachromosomal, circular DNA episomes, which replicates synchronously with the host cell, establishing a latent infection; (2) conversion from latent into productive infection with assembly of complete infective virions; (3) integration of viral DNA into host cellular genome, a phenomenon seen in HPV infections associated with malignant transformation. Human papillomaviruses (HPVs) essentially induce skin and mucosal epithelial lesions. Various skin warts are well known to be HPV-associated (HPVs 1, 2, 3, 7 and 10). Besides HPVs 3 and 10, HPVs 5, 8, 17 and 20 have been recovered from Epidermodysplasia verruciformis lesions. Anogenital condyloma acuminatum, strongly linked with HPVs 6 and 11 are probably sexually transmitted. The same HPVs, demonstrable in recurrent juvenile laryngeal papillomas, are probably transmitted by passage through an infected birth canal. HPVs described in uterine cervical lesions are generally categorized into those associated with high (16, 18), intermediate (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) and low (6, 11, 26, 40, 42, 43, 44, 53, 54, 55, 62, 66) risk of cervical squamous carcinoma. Cervical adenocarcinoma, clear cell carcinoma and small cell neuroendocrine carcinoma have also been linked to HPVs, especially HPV18. Other lesions reported to be HPV-associated are: papillomas, dysplasia and carcinomas in the nasal cavity (HPV 6, 11, 57); squamous papilloma, condyloma acuminatum, and verruca vulgaris of the oral cavity (HPV 6, 11), oral focal epithelial hyperplasia (HPV 13, 32); warty lip lesions (HPV 2): and conjunctival papillomas (HPV 6, 11).
The objective of this study was to ascertain the extent changes have occurred in the epidemiology of human rotavirus electropherotypes from the same location 7 to 8 years after an earlier study. Genomic RNA profiles of rotaviruses from diarrhoeic children admitted to the Kuala Lumpur Hospital from April to December 1996 were determined by polyacrylamide gel electrophoresis and silver staining. A total of 179 group A rotaviruses were detected from 870 children: 175 with legible staining of all RNA segments were classified into 14 distinct electropherotypes (10 and 4 with long and short migration patterns respectively). In addition, the results revealed: high predominance of long pattern electropherotypes (94% of the total electropherotypes); most long electropherotypes with RNA profiles which all 11 RNAs migrated separately (8 of 10 electropherotypes); all short electropherotypes had segments 2 and 3 that co-migrated; presence of a very numerically dominant electropherotype (75% of all electropherotypes); frequent co-circulation of the dominant electropherotype-present throughout the study period--with other electropherotypes present for limited periods; sequential temporal appearances by similar electropherotypes. These observations were similar to that of an earlier study conducted in 1988/89. Nevertheless, the dominant electropherotype in the present study was different and not among the electropherotypes detected in the earlier study.
Eighty-six infiltrating ductal carcinoma of breast were studied by the standard avidin-biotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, for oestrogen receptor (ER) protein and c-erbB-2 oncoprotein expression. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. 21% tumours were ER positive while 44% were c-erbB-2 positive. Of ER positive tumours, 33.3% were c-erbB-2 positive whereas the c-erbB-2 positivity rate was much higher (47.1%) in ER negative tumours. Only 16% of c-erbB-2 positive tumours were ER positive while 25% of c-erbB-2 negative tumours were ER positive. This negative relationship between ER and c-erbB-2 expression was statistically significant (Mc Nemar's test, p < 0.005). The ER positivity rate did not vary significantly with histological grade. However, c-erbB-2 overexpression was significantly more prevalent in grade III tumours compared with grade I and II tumours (Chi-square test, p < 0.005). Since the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor (EGFR) gene, we expect that c-erbB-2 oncoprotein would share functional similarities with EGFR leading to both loss of oestrogen receptor and poor prognosis in breast cancer. Its overexpression can be expected to relate to more aggressive tumour proliferation and may explain its correlation with high histological grade, a known indicator of aggressive cancer behaviour. As there is no indication that ER protein activity contributes to advancement in histological grade, it would appear that cellular dedifferentiation precedes ER loss during malignant transformation. It has been mooted that ER positive breast cancers which also show c-erbB-2 oncoprotein overexpression have a poorer response to hormonal therapy. The use of this parameter in the routine assessment of breast cancer patients may identify subsets of patients for more aggressive therapy.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by increased B cell activity and depressed T cell function. However, the contribution of the immunoregulatory system to its pathogenesis is still unclear. The recent development in the production of monoclonal antibodies and the availability of bench-top flow cytometers have allowed rapid quantitation of peripheral blood lymphocyte subsets. We analysed the distribution of the lymphocyte subsets in 24 patients with active SLE and 18 with inactive SLE. The distribution of immunoregulatory cells in 72 normal volunteers was used as control. Statistical analysis showed that there were significant differences between both the SLE groups and the normal controls, for total lymphocytes, T cells, B cells, T helper cells, T suppressor cells, T helper/suppressor ratio and natural killer cells. There was a significant difference for T helper cells between active and inactive SLE. T helper cells levels were found to be low in inactive SLE and lower in active SLE. It appears that treatment-induced remissions did not restore the levels of immunoregulatory cells to normal. Thus, T helper cell levels reflect disease activity and longitudinal assays of T helper cells may serve as an indicator of disease reactivation.
Thirty-eight cases of lupus nephritis, all satisfying the American Rheumatism Association criteria for diagnosis of systemic lupus erythematosus (SLE), with renal involvement and biopsy were immunohistochemically studied for the expression of HLA-DR (DAKO: HLA-DR/alpha, TAL.1B5), one of the three known families belonging to the class II major histocompatibility complex (MHC), using a standard streptavidin-biotin-peroxidase method. 20 nephrectomies performed for renal trauma and tumours constituted the normal controls. Of the lupus nephritis cases, 34 were females and 4 males. Ethnically, 20 were Chinese, 13 Malay, 4 Indian and 1 of indigenous origin. Their ages ranged from 16 to 59 years (mean of 31 years). Histologically, 23 expressed World Health Organisation (WHO) class IV (diffuse proliferative), 10 WHO class V (diffuse membranous), 4 WHO class II (pure mesangiopathy) and 1 WHO class III (segmental and focal proliferative) nephritis. Activity scores ranged between 5 to 19 (mean = 8.6) and chronicity scored between 2 to 7 (mean = 3.2) on a standard scoring system. Similar to other studies, HLA-DR was expressed in the glomerular capillaries and peritubular capillaries of all and mesangium, tubules (proximal, distal and collecting), veins and arterioles of some normal controls. Interestingly, HLA-DR expression was noted in the arteries of 25% of the normal controls, a finding hitherto not reported. The frequency of lupus nephritis cases expressing HLA-DR in the various anatomical components did not differ significantly from the normal controls except that HLA-DR expression in arteries and arterioles was seen at a significantly increased frequency (p < 0.01) in lupus nephritis. This increased expression did not correlate with the WHO class, activity or chronicity scores. It therefore appears that MHC class II shows increased expression in the arterial system of lupus nephritis kidneys. The significance of this is unclear but could be related to heightened (gamma-interferon activation which may be a de novo phenomenon or result of T cell proliferation and activation in SLE.
Platelet transfusions are indicated in a wide variety of clinical conditions especially those with thrombocytopenia. However, without proper clinical practice guidelines, inappropriate transfusions are bound to happen. To ascertain the provision of a quality and appropriate practice of platelet transfusions, an audit study was carried out over a period of one month at the Paediatric Institute, Kuala Lumpur Hospital. A prospective audit was performed during that period whilst a retrospective collection of data was carried out for the previous month for comparison. Based on a set of criteria agreed upon by the audit committee, it was found that in 18.5% (22 of 119) of the cases, the indications for platelet transfusions were inappropriate. The audit committee concluded that there is a need for a more detailed clinical practice guideline for local use to reduce or lower the incidence of inappropriate transfusions of platelets.
A chromatographic immunoassay cholera antigen detection kit, the Cholera Spot test, was evaluated. The test was found to be specific with a sensitivity of 10(6) cfu/ml for the direct detection of V. cholerae in simulated stool specimens and 10 cfu/ml in simulated cotton-tipped swab specimens after overnight incubation in alkaline peptone water. This enables early recognition of cholera cases and their contacts so that prevention and control measures can be promptly instituted.
The duty of confidentiality in the normal doctor-patient relationship is well recognized. However, the duty of confidentiality between the pathologist who performs the autopsy and the requesting authorities and the next-of-kin is not as clearly spelt out. This article discusses the problems faced by the pathologist with regards to hospital and medico-legal autopsies in Malaysia. A proposed ethical guideline is included on how to deal with peculiar issues regarding confidentiality and the pathologist.
All deaths due to unnatural causes and deaths that are believed to be due to natural causes but where the medical cause of death is not certain or known are subjected to an inquest. The objective of an inquest is to ascertain facts pertaining to the death. This is achieved by inquiry and at the conclusion of the inquest a verdict is arrived as to whether the death was due to a natural, accidental, suicidal or a homicidal cause. An inquest is not a trial. There is no complainant or defendant and at the conclusion of the inquest no judgment is passed. The inquest system exists in all parts of the world. In the English legal system, the person who conducts an inquest is called a Coroner. In Scotland, he is called a Procurator Fiscal. The United States of America use the Medical Examiner system. Most continental European countries and their former colonies follow the Code Napoleon. A postmortem examination may become necessary in certain deaths that come up for inquests. In these situations the authority which conducts the inquest will order a doctor to perform a postmortem examination (medico-legal autopsy). To perform a medico-legal autopsy, consent from the relatives of the deceased is not required. In an unexpected sudden death, only a doctor after a postmortem examination may be able to determine the cause of death. However, it is often wrongly assumed that the objective of a postmortem examination is only to ascertain the cause of death. This article deals with the purpose of the inquest and roles of the medico-legal autopsy.
Primary mucoepidermoid carcinoma (MEC) of thyroid is an uncommon tumour and reports on its' cytology are consequently scanty. A 46-year-old male presented with a thyroid nodule of nine months duration. Fine needle aspiration (FNA) cytology of the nodule showed features of a malignant tumor that was different from the usual types of thyroid carcinoma. Monolayers and syncytial clusters of round and spindle tumour cells with large vesicular nuclei and single macronucleoli were present. A diagnosis of carcinoma was given with the comment that this was unlike any of the usual types of thyroid cancer and that a metastatic malignancy should be ruled out. The cytological picture of MEC may not always be distinctive enough for accurate tumour typing. Nevertheless the cytological features are usually sufficiently different to rule out all of the usual types of thyroid carcinoma. This distinction may be important from the point of view of differing prognosis in MEC of thyroid (as compared to differentiated thyroid cancers) and the need to exclude a metastatic carcinoma, especially from a primary in one of the salivary glands.
A 32-year-old pregnant lady presented with a rapidly enlarging right breast mass. A fine needle aspiration was suggestive of a malignant phylloides tumour. However histopathological examination after mastectomy revealed a moderately differentiated angiosarcoma. The histopathological and cytological features of this rare tumour together with the diagnostic pitfalls are discussed.
Suicide is one of the ten leading causes of death in the world, accounting for more than 400,000 deaths annually. The pattern of suicide and the incidence of suicide vary from country to country. Cultural, religious and social values play some role in suicide. Compared to the West and some of the countries in the Asian region the incidence of suicide is low in Malaysia. A three-year retrospective study of all the autopsies performed at the University Hospital, Kuala Lumpur was analysed and the cases that were definitely determined as suicides were further studied. 48.8% of all suicides were ethnic Indians though Indians formed only 8% of the Malaysian population. 38.1% of suicides were Chinese who formed 26% of the population while only 3.6% were Malays, who formed 59% of the population. The preferred methods of suicide were poisoning and hanging. The majority were in the age group 20-40 yr. The study may have missed some cases that would have been wrongly concluded as accidental deaths and a few others where the police would have released the bodies without postmortem examinations.
Lymph node excision biopsy is commonly carried out for the investigation of lymphadenopathy. The objective of this study is to elucidate the pattern of nodal pathology seen in a private pathology practice. A total of 137 nodal biopsies for primary investigation of nodal enlargement were retrieved from the files in a private diagnostic pathology laboratory in the year 1997. Lymph nodes excised for cancer staging were excluded from this study. The histology was reviewed based on H&E stained sections, and with additional histochemical and immunoperoxidase stains when deemed necessary. Cases of malignant lymphomas were sub-classified with the aid of further immunophenotyping using a panel of monoclonal and polyclonal lymphoid antibodies. One case was excluded from this study due to inadequate tissue for further assessment. There were 58 males and 78 females, giving a ratio of 1:1.3 in the remaining 136 cases. They consisted of 13 Malays (M), 108 Chinese (C), 14 Indians (I) and 1 other ethnic group (O). The ratio of M:C:I:O was 1:8.3:1.1:0.1. The majority of the cases were in the age range of 20 to 50 years. The pathology consisted of 17 (12.5%) malignant lymphomas [6 Hodgkin's lymphoma, 11 non-Hodgkin's lymphoma], 35 (25.7%) metastatic carcinomas, 45 (33.1%) reactive hyperplasia, 19 (13.9%) tuberculosis, 11 (8.2%) Kikuchi's disease and 9 (6.6%) others (Castleman's disease 2, cat scratch disease 2, Kimura's disease 1, sarcoidosis 1, non-specific lymphadenitis 3). All categories of nodal disease showed approximately similar ratio of ethnic and gender distribution as above, except for Kikuchi's disease, for which 100% of the patients were female. The most common site of biopsy was from the head and neck region, particularly the cervical group of nodes. The most common nodal pathology seen in the private laboratory was reactive hyperplasia, followed by metastatic carcinoma. Malignant lymphoma constituted only 12.5% of the cases.
An 86-year-old man presented with a painless, pea-sized growth over the left angle of his jaw, which had been gradually enlarging over two years. A clinical diagnosis of pilar cyst was made. Histopathological examination of the mass revealed a malignant proliferating trichilemmal tumour. During follow-up 4 months later, a palpable small upper jugular lymph node was noted at the left side of the neck. Biopsy revealed a metastatic malignant trichilemmal tumour. This case illustrates a rare malignant tumour which is a challenge to clinical diagnosis.