It has been almost two decades ago since the first AIDS case was reported in Malaysia. It has also been approximately eight years ago when the method of backcalculation was used to estimate the past HIV infection rate from the AIDS incidence data and an estimate of the incubation period distribution. This method is used because it makes use of the Malaysian AIDS incidence which is fairly reliable and reflects the trend of the epidemic as compared to the HIV infection rate recorded. The latest results generated show a slowdown in the increase of the number of estimated infected HIV+ cases in the late 1990s and this trend is supported by a slowdown in the increase of the number of AIDS cases recorded.
MeSH terms: Acquired Immunodeficiency Syndrome/epidemiology; Data Interpretation, Statistical; Humans; Malaysia/epidemiology; Models, Theoretical; Risk Factors; Time Factors; HIV Infections/epidemiology*; Incidence; Risk Assessment; Sentinel Surveillance*
Precision Radiotherapy at high doses require a fixed, referable target point. The frame system fulfills the required criteria by making the target point relocatable and fixed within a stereotactic space. Since December 2001, we have treated 28 central and peripheral nervous system lesions using either radiosurgery as a single high dose fraction or fractionated 3-dimensional conformal radiotherapy using a lower dose and a multi-leaf collimator. Various pathological lesions either benign or malignant were treated. Eighty six percent of our treated lesions showed growth restraint, preventing them from causing new symptoms with a median follow-up duration of 20.5 months. However, the true benefit from this technique would require a long-term follow-up to document the progress.
Congenital upper airway obstruction is a relatively rare but important cause of major respiratory problems in the neonatal period. Vocal cord paralysis is the second most common cause of congenital airway obstruction presenting with neonatal stridor. It is often the reason for the failure of neonates to wean from the respiratory support. A retrospective analysis of medical record review was conducted. There were seven paediatric patients diagnosed with bilateral vocal fold paralysis in the past three years, of which five were recently diagnosed. All patients underwent flexible with/without rigid bronchoscopes to confirm the diagnosis. This case series highlight our experience in managing the problem of bilateral vocal cord paralysis in the paediatric population, with particular emphasis on their clinical presentations, associated complications and both upper and lower airway abnormalities. The management options and outcome of these patients will also be discussed.
A patient with beta hCG-secreting germ cell carcinoma of the pineal and suprasellar regions presented with hydrocephalus, Parinaud's syndrome, hypopituitarism and polyuria. Central diabetes insipidus was strongly suspected although the water deprivation test was not diagnostic. The polyuria however, responded to ADH analogue when the hypothyroidism and hypocortisolism were treated. Pubertal development was evident and serum testosterone was normal despite the low FSH/LH, suggesting hCG stimulation of Leydig cells. This case illustrates that a beta hCG-germ cell tumour of the suprasellar region causing hypopituitarism can mask the presence of central diabetes insipidus and hypogonadotrophic hypogonadism.
MeSH terms: Adult; Humans; Hypogonadism/diagnosis*; Hypogonadism/pathology; Hypopituitarism/diagnosis*; Hypopituitarism/etiology; Male; Neoplasms, Germ Cell and Embryonal/complications; Neoplasms, Germ Cell and Embryonal/diagnosis*; Neoplasms, Germ Cell and Embryonal/pathology; Pineal Gland/pathology; Polyuria; Water Deprivation; Fatal Outcome; Diabetes Insipidus, Neurogenic/diagnosis*; Diabetes Insipidus, Neurogenic/pathology
A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.
Epiglottic cyst is usually asymptomatic and the commonest presentation is foreign body sensation in the throat. Treatment of epiglottic cysts depends on their size and on the clinical symptoms. Surgery is necessary for large ones. Various modalities of therapy include endoscopic excision, marsupialization and deroofing with or without a carbon dioxide laser. We report our experience of managing a case of a large epiglottic cyst with a carbon dioxide laser.
We report a case of a 65 year old Malay lady with long-standing diabetes mellitus, who presented to our institution with a one month history of worsening neck pain and progressive upper and lower limb weakness. She was stable despite severe hyponatraemia which was initially treated as syndrome of inappropriate anti-diuretic hormone (SIADH). This was consistent with her underlying illness which was concluded as cervical tuberculosis (TB) with spinal cord compression. She underwent decompression and bone grafting. Despite continuous treatment her serum sodium levels remained low. There were no other problems with her adrenals or thyroid. A water loading and hypertonic saline perfusion test was performed and supported the diagnosis of reset osmostat. Her serum sodium remained below the normal range and she was discharged well.
We report a case of an adult who presented with progressive swelling in the right eye with suggestive of intracranial lesion on imaging. Histopathological revealed a lacrimal gland malignant mixed tumour.
Intranasal haemangioma is quite rare. This tumor may be confused with other intranasal vascular tumor such as juvenile nasopharyngeal angiofibroma (JNA), glomus tumors as well as other tumor such as angiosarcoma and leiomyoma. Juvenile nasopharyngeal angiofibroma is the most common vascular tumor encountered in nasal cavity. A definitive histology diagnosis pre-operatively is difficult to be obtained as the biopsy may lead into severe uncontrolled bleeding. The final diagnosis very much depends on histology after the tumor excision. Complete surgical resection of the tumor is the standard approach. In this report we describe our surgical management in approaching intranasal haemangioma endoscopically and this pathology can be considered as one of differential diagnosis for unilateral nasal mass.
Underwater and Hyperbaric Medicine is a treatment modality gaining recognition in Malaysia. It uses the hyperbaric oxygen therapy (HBOT) approach where patients are placed in recompression chambers and subjected to oxygen therapy under pressure. In Malaysia it was introduced as early as the 1960's by the Royal Malaysian Navy to treat their divers for decompression illness (DCI), arterial gas embolism (AGE) and barotraumas. Other sectors in the armed forces, universities and private health centres began developing this approach too in the late 1990's, for similar purposes. In 1996, Underwater and Hyperbaric Medicine began gaining its popularity when the Institute of Underwater and Hyperbaric Medicine at the Armed Forces Hospital in Lumut started treating specific clinical diseases such as diabetic foot ulcers, osteomyelitis, and carbon monoxide poisoning and other diseases using HBOT. This paper discusses the development of this interesting treatment modality, giving a brief historical overview to its current development, as well as provides some thought for its future development in Malaysia.
Postpartum is a crucial period for a mother. During this period a mother is going through the physiological process of uterine involution and at the same time adapting to her new role in the family. Many postpartum complications occur during this period. Among the important obstetric morbidities are postpartum hemorrhage, pregnancy related hypertension, pulmonary embolism and puerperal sepsis. Common surgical complications are wound breakdown, breast abscess and urinary fecal incontinence. Medical conditions such as anemia, headache, backache, constipation and sexual problems may also be present. Unrecognized postpartum disorders can lead to physical discomfort, psychological distress and a poor quality of life for the mothers. Providing quality postnatal care including earlier identification of the problems (correction) and proper intervention will help the mother to achieve full recovery and restore her functional status back to the pre-pregnancy state sooner.
Sixteen low grade (LSIL), 22 high grade (HSIL) squamous intraepithelial lesions, 28 invasive (13 stage I and 15 stage II-IV) squamous cell carcinoma (SCC) and 15 benign cervices were immunohistochemically studied for involvement of Bcl-2 and Bax proteins in cervical carcinogenesis. 4-microm sections of the cases were immunostained for Bcl-2 (Clone 124: Dako) and Bax (Dako) and staining intensity was rated as 1 (light), 2 (moderate) and 3 (strong) and percentage cellular staining as 0 (negative), 1 (1-25%), 2 (26-50%), 3 (51-75%) and 4 (>75%) with score derived by multiplying staining intensity and percentage positivity. The cut-off value, indicating upregulated expression, was computed as >2 for Bcl-2 and >8 for Bax. Bcl-2 was upregulated (p < 0.05) in HSIL and Bax in SCC when compared with benign cervical squamous epithelium. Bcl-2 expression was confined to the lower third of the epithelium in the benign cervices and LSIL. In HSIL, expression reached the middle and upper thirds. 4 (30.8%) HSIL with upregulated Bcl-2 demonstrated intensification of staining around the basement membrane. SCCs showed "diffuse" (evenly distributed) or "basal" (intensified staining around the periphery of the invading tumour nests) expression of Bcl-2. Of the 5 SCCs with upregulated Bcl-2, 1 of 2 (50%) stage I and 3 (100%) stage II-IV tumours exhibited the "basal" pattern. Benign cervical squamous epithelium, LSIL, HSIL and SCC showed a generally diffuse Bax expression. Thus, Bcl-2 and Bax appeared to be upregulated at different stages of cervical carcinogenesis, Bcl-2 in HSIL and Bax after invasion. Intensification of staining of Bcl-2 at the basement membrane in some HSIL and SCC is interesting and may augur for increased aggressiveness.
Familial hypercholesterolaemia (FH) and Familial defective apolipoprotein B100 (FDB) are autosomal dominant inherited diseases of lipid metabolism caused by mutations in the low density lipoprotein (LDL) receptor and apolipoprotein B 100 genes. FH is clinically characterised by elevated concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), presence of xanthomata and premature atherosclerosis. Both conditions are associated with coronary artery disease but may be clinically indistinguishable. Seventy-two (72) FH patients were diagnosed based on the Simon Broome's criteria. Mutational screening was performed by polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE). Positive mutations were subjected to DNA sequencing for confirmation of the mutation. We successfully amplified all exons in the LDL receptor and apo B100 genes. DGGE was performed in all exons of the LDL receptor (except for exons 4-3', 18 and promoter region) and apo B100 genes. We have identified four different mutations in the LDL receptor gene but no mutation was detected in the apo B 100 gene. The apo B100 gene mutation was not detected on DGGE screening as sequencing was not performed for negative cases on DGGE technique. To our knowledge, the C234S mutation (exon 5) is a novel mutation worldwide. The D69N mutation (exon 3) has been reported locally while the R385W (exon 9) and R716G (exon 15) mutations have not been reported locally. However, only 4 mutations have been identified among 14/72 patients (19.4%) in 39 FH families. Specificity (1-false positive) of this technique was 44.7% based on the fact that 42/76 (55.3%) samples with band shifts showed normal DNA sequencing results. A more sensitive method needs to be addressed in future studies in order to fully characterise the LDLR and apo B100 genes such as denaturing high performance liquid chromatography. In conclusion, we have developed the DNA analysis for FH patients using PCR-DGGE technique. DNA analysis plays an important role to characterise the type of mutations and forms an adjunct to clinical diagnosis.
MeSH terms: Adolescent; Adult; Aged; Base Sequence; Child; Child, Preschool; DNA Mutational Analysis; Female; Genetic Testing/methods*; Humans; Hyperlipoproteinemia Type II/genetics*; Male; Middle Aged; Mutation; Receptors, LDL/genetics*; Sensitivity and Specificity; Electrophoresis, Gel, Two-Dimensional/methods*; Polymerase Chain Reaction; DNA Primers; Apolipoprotein B-100/genetics*
The molecular basis of variable phenotypes in P-thalassaemia patients with identical genotypes has been associated with co-inheritance of alpha-thalassaemia and persistence of HbF production in adult life. The Xmn I restriction site at -158 position of the Ggamma-gene is associated with increased expression of the Ggamma-globin gene and higher production of HbF This study aims to determine the frequency of the digammaferent genotypes of the Ggamma Xmn I polymorphism in P-thalassaemia patients in two ethnic groups in Malaysia. Molecular characterisation and frequency of the Ggamma Xmn I polymorphism were studied in fifty-eight Chinese and forty-nine beta-thalassaemia Malay patients by Xmn I digestion after DNA amplification of a 650 bp sequence. The in-house developed technique did not require further purification or concentration of amplified DNA before restriction enzyme digestion. The cheaper Seakem LE agarose was used instead of Nusieve agarose and distinct well separated bands were observed. Genotyping showed that the most frequent genotype observed in the Malaysian Chinese was homozygosity for the absence of the Xmn I site (-/-) (89.7%). In the Malays, heterozygosity of the Xmn I site (+/-) was most common (63.3%). Homozygosity for the Xmn I site (+/+) was absent in the Chinese, but was confirmed in 8.2% of the Malays. The ratio of the (+) allele (presence of the Xmn I site) to the (-) allele (absence of the Xmn I site)) was higher in the Malays (0.66) compared to the Chinese (0.05). The (+/-) and (+/+) genotypes are more commonly observed in the Malays than the Chinese in Malaysia.
MeSH terms: Humans; Malaysia/ethnology; Polymorphism, Genetic*; Deoxyribonucleases, Type II Site-Specific/genetics*; Polymerase Chain Reaction/methods*; beta-Thalassemia/genetics*; Asian Continental Ancestry Group
Hearing loss is a common sensory deficit in humans. The hearing loss may be conductive, sensorineural, or mixed, syndromic or nonsyndromic, prelingual or postlingual. Due to the complexity of the hearing mechanism, it is not surprising that several hundred genes might be involved in causing hereditary hearing loss. There are at least 82 chromosomal loci that have been identified so far which are associated with the most common type of deafness--non-syndromic deafness. However, there are still many more which remained to be discovered. Here, we report the mapping of a locus for autosomal recessive, non-syndromic deafness in a family in Malaysia. The investigated family (AC) consists of three generations--parents who are deceased, nine affected and seven unaffected children and grandchildren. The deafness was deduced to be inherited in an autosomal recessive manner with 70% penetrance. Recombination frequencies were assumed to be equal for both males and females. Using two-point lod score analysis (MLINK), a maximum lod score of 2.48 at 0% recombinant (Z = 2.48, theta = 0%) was obtained for the interval D14S63-D14S74. The haplotype analysis defined a 14.38 centiMorgan critical region around marker D14S258 on chromosome 14q23.2-q24.3. There are 16 candidate genes identified with positive expression in human cochlear and each has great potential of being the deaf gene responsible in causing non-syndromic hereditary hearing loss in this particular family. Hopefully, by understanding the role of genetics in deafness, early interventional strategies can be undertaken to improve the life of the deaf community.
This study reports the results of mutation detection of tumour suppressor genes, p53 and RB2/p130 genes in Malaysian nasopharyngeal carcinoma (NPC) studied by PCR-CSGE analysis and direct DNA sequencing method. Frequent sites of mutation in both genes (exons 5-8 of p53 and exons 19-21 of RB2/p130) were examined. Thirty-six NPC blood samples and three NPC cell lines were investigated for the presence of mutations. No mutation of p53 and RB2/p130 genes was identified in any of the blood samples. Nonetheless, there was an identical G-->4 C nucleotide change at codon 280 of p53 gene in all the cell lines. A larger study that includes biopsy tissues should be carried out to provide a more in-depth look into the pathogenesis of NPC in Malaysia.
MeSH terms: DNA Mutational Analysis; Humans; Malaysia; Nasopharyngeal Neoplasms/genetics*; Electrophoresis, Gel, Two-Dimensional; Polymerase Chain Reaction; Tumor Suppressor Protein p53/genetics*; Point Mutation; Retinoblastoma-Like Protein p130/genetics*
Catheterization of the umbilical artery has been a useful aid in the management of sick neonates for the past few decades. However, it is associated with various complications. Reported studies strongly suggest a significant role of intravascular catheterization in the development of aortic thrombi. Increase in thrombosis of large vessels is believed to be related to mechanical injury in the catheterized vessels, which provide direct exposure of blood to tissue factor (TF), the primary cellular initiator of the extrinsic coagulation pathway. This study was conducted to determine the levels of plasma TF, tissue factor pathway inhibitor (TFPI) and D-dimer (DD) in infants with umbilical arterial catheter (UAC)-associated thrombosis. Quantification of TF was carried out using an in-house sandwich ELISA, whereas TFPI and DD levels were measured with commercial immunoassay kits. Infants with UAC inserted were found to have significantly higher levels of plasma TF (p < 0.001) than baseline levels. However, there were no significantly elevated levels of TFPI or DD. Infants with UAC-associated thrombosis demonstrated a greater increase of TF level (median: 414.5 pg/mL; range: -76.0, 6667.0) than infants without UAC-associated thrombosis (105.0 pg/mL; -976.0, 9480.0; p = 0.009) following UAC insertion. Our findings indicate that quantification and monitoring of TF levels could predict thrombus formation in infants with indwelling UAC. Following umbilical arterial catheterisation, infants with an approximately 3-fold rise in plasma TF levels were most at risk of developing abdominal aorta thrombosis as confirmed by real-time abdominal ultrasonography.
Edwardsiella tarda has recently been described as a member of the family Enterobacteriaceae. The genus Edwardsiella contains three species; E. hoshinae, E. ictaluri and E. tarda. Edwardsiella tarda is the only species which has been recognised as pathogenic to humans, especially in those with an underlying disease. The most common presentation is watery diarrhoea. Extra intestinal infections have been reported infrequently. Humans seem to be infected or colonised with Edwardsiella through ingestion or inoculation of a wound. This report is of a patient with multiple liver abscesses due to E. tarda who later developed bacterial peritonitis and septicaemic shock.
Intense myelofibrosis is rarely associated with de novo acute myeloid leukaemia (AML) except in acute megakaryoblastic leukaemia (AML-M7) where there is diffuse marrow fibrosis as a consequence of proliferation of neoplastic myeloid cells. AML associated with significant myelofibrosis developing both de novo or secondary to primary (idiopathic) myelofibrosis is characterised by a fulminant course and extremely poor prognosis, primarily due to treatment-resistant disease. The prognostic value of degree of marrow fibrosis in de novo AML has been poorly investigated. We describe a case of extensive myelofibrosis associated with acute erythroblastic leukaemia (AML-M6) that responded to induction therapy of the leukaemia.
Hepatocellular carcinoma (HCC) is among the ten most common cancers in Malaysian males. As cellular proliferation is an important feature of malignant transformation, we studied the proliferation pattern of normal and benign perineoplastic liver versus hepatocellular carcinoma in an attempt to further understand the tumour transformation process. 39 HCC (21 with accompanying and 18 without cirrhosis) histologically diagnosed at the Department of Pathology, University of Malaya Medical Centre between January 1992 and December 2003 were immunohistochemically studied using a monoclonal antibody to PCNA (Clone PC10: Dako). 20 livers from cases who had succumbed to traumatic injuries served as normal liver controls (NL). PCNA labeling index (PCNA-LI) was determined by counting the number of immunopositive cells in 1000 contiguous HCC, benign cirrhotic perineoplastic liver (BLC), benign perineoplastic non-cirrhotic (BLNC) and NL cells and conversion to a percentage. The PCNA-LI was also expressed as Ojanguren et al's grades. PCNA was expressed in 10% NL, 38.9% BLNC, 76.2% BLC and 71.8% HCC with BLNC, BLC and HCC showing significantly increased (p < 0.05) number of cases which expressed PCNA compared with NL. The number of BLC which expressed PCNA was also significantly increased compared with BLNC. PCNA-LI ranged from 0-2.0% (mean = 0.2%) in NL, 0-2.0% (mean = 0.3%) in BLNC, 0-3.6% (mean = 0.7%) in BLC and 0-53.8% (mean = 7.6%) in HCC with PCNA-LI significantly increased (p < 0.05) only in HCC compared with BLC, BLNC and NL. Accordingly, all NL, BLC and BLNC showed minimal (<5% cells being immunopositive) immunoreactivity on Ojanguren et al's grading system and only HCC demonstrated immunoreactivity which ranged up to grade 3 (75% of cells). From this study, there appears to be a generally increasing trend of proliferative activity from NL to BLNC to BLC and HCC. Nonetheless, BLNC and BLC, like NL, retained low PCNA-LI and only HCC had a significantly increased PCNA-LI compared with the benign categories. This is probably related to the malignant nature of HCC and may reflect the uncontrolled proliferation of the neoplastic hepatocytes.