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Comparison of Sybr Green I, ELISA and conventional agarose gel-based PCR in the detection of infectious bursal disease virus

Hairul Aini H, Omar AR, Hair-Bejo M, Aini I

Microbiol Res, 2008;163(5):556-63.
PMID: 16971101

The current available molecular method to detect infectious bursal disease virus (IBDV) is by reverse transcriptase-polymerase chain reaction (RT-PCR). However, the conventional PCR is time consuming, prone to error and less sensitive. In this study, the performances of Sybr Green I real-time PCR, enzyme-linked immunosorbent assay (ELISA) and conventional agarose detection methods in detecting specific IBDV PCR products were compared. We found the real-time PCR was at least 10 times more sensitive than ELISA detection method with a detection limit of 0.25pg. The latter was also at least 10 times more sensitive than agarose gel electrophoresis detection method. The developed assay detects both very virulent and vaccine strains of IBDV but not other RNA viruses such as Newcastle disease virus and infectious bronchitis virus. Hence, Sybr Green I-based real-time PCR is a highly sensitive assay for the detection of IBDV.

Matched MeSH terms: Infectious bursal disease virus/genetics; Infectious bursal disease virus/isolation & purification*
Unilateral moyamoya disease with co-existing arteriovenous malformation

Nawawi O, Sinnasamy M, Ramli N

Br J Radiol, 2006 Jul;79(943):e12-5.
PMID: 16823046

A case of an intracerebral bleed in a young man with a rare combination of arteriovenous malformation (AVM) and unilateral moyamoya disease is presented. The location of the bleed in the left basal ganglia corresponded to the area supplied by the basal moyamoya vessels. The AVM which received supply from collateral moyamoya vessels as well as normal cerebral arteries was located in the ipsilateral parieto-occipital region posterior to the basal ganglia bleed. This is the first reported cerebral AVM co-existing with a unilateral moyamoya disease in the English literature. Unusual features of the case such as the unilaterality of the angiographic abnormalities, their coexistence and hypotheses as to their development are discussed.

Matched MeSH terms: Moyamoya Disease/complications*; Moyamoya Disease/radiography
Fulltext Deaths in children during an outbreak of hand, foot and mouth disease in Peninsular Malaysia--clinical and pathological characteristics

Shekhar K, Lye MS, Norlijah O, Ong F, Looi LM, Khuzaiah R, et al.

Med J Malaysia, 2005 Aug;60(3):297-304.
PMID: 16379183

From July through December 1997, 11 previously healthy children in Peninsular Malaysia succumbed to an illness clinically characterised by an acute severe refractory left-ventricular failure, following a brief prodromal illness, in the midst of an outbreak of hand, foot and mouth disease (HFMD), similar to the reported experience in Sarawak and Taiwan. Retrospective reviews of the clinical features and results of laboratory, pathological and virological investigations of cases were conducted. The median age of the 11 case-patients was 31 months (range, 13 to 49 months); 6 were males. A brief prodromal illness of 3 days (range, 2 to 5 days) was characterised by fever (axillary temperature > 38 degrees C) (100%), oral ulcers (72%), extremity rashes (45%) and significant vomiting (55%). Upon hospitalisation, 7 of 11 case-patients had features suggestive of cardiogenic shock, while 4 of 11 case-patients developed shock during hospitalisation as evidenced by marked sustained tachycardia (heart rate > or = 180 beats per minute), poor peripheral pulses and peripheral perfusion, mottled extremities, pulmonary oedema (haemorrhagic pulmonary secretions in 8 of 11 cases during tracheal intubation, often precipitated by conservative crystalloid boluses, and radiographic evidence of acute pulmonary oedema in 5 of 7 cases) and markedly impaired left ventricular function on echocardiographic examination (7 of 7 cases). Three of 4 case-patients had aseptic meningitis while one case-patient also had an acute flaccid paraparesis. Despite supportive therapy, death occurred within a median of 13.4 hours following hospitalization. Post-mortem findings (all 8 specimens examined) consistently demonstrated brain-stem encephalitis with foci of neuronal necrosis and micro-abscesses. None of the 11 specimens examined revealed histological evidence of myocarditis. Enterovirus 71 (EV71) was detected in 10 of 11 case-patients, many (7) from various sterile tissue sites (5 from central nervous tissues). No other viruses were isolated or identified. Clinical features and pathological studies closely paralleled the reported experience in Sarawak and Taiwan. The uniform necropsy findings of necrotizing brain-stem encephalitis coupled with essentially normal myocardial histology, in concert with the concurrent and consistent detection of EV71 points to a primary EV71 encephalitis; as yet unclear neurogenic mechanisms may account for the cardiovascular manifestations.

Matched MeSH terms: Hand, Foot and Mouth Disease/mortality*; Hand, Foot and Mouth Disease/pathology*
Characterization of Malaysian velogenic NDV strain AF2240-I genomic sequence: a comparative study

Murulitharan K, Yusoff K, Omar AR, Molouki A

Virus Genes, 2013 Jun;46(3):431-40.
PMID: 23306943 DOI: 10.1007/s11262-012-0874-y

Newcastle disease virus (NDV) strain AF2240 is a viscerotropic velogenic strain that is used as a vaccine challenge virus in Malaysia. The identification of the full length genome will be a crucial platform for further studies of this isolate. In this study, we fully sequenced the genome of a derivative of this strain named AF2240-I. The 15,192 nt long genome contains a 55-nt leader sequence at the 3' whereas the trailer region consists of 114 nt at the 5'. The intergenic sequences between the NP-P, P-M, M-F, F-HN, and HN-L genes comprise 1, 1, 1, 31, and 47 nt, respectively. The acknowledged cleavage site of fusion protein showed amino acid sequence of 112-R-R-Q-K-R-F-117, which corresponds to those of virulent NDV strains. Phylogenetic analysis of the whole virus genome shows that the strain AF2240-I belongs to genotype VIII and is more closely related to velogenic strains QH1, QH4, Fontana, Largo, and Italienas compared to other strains of NDV. Differences are noticed in the hemagglutinin-neuraminidase (HN) and matrix (M) gene between AF2240 and its derivative AF2240-I. This is the first report of a complete genome sequence of an NDV strain isolated in Malaysia.

Matched MeSH terms: Newcastle disease virus/genetics*; Newcastle disease virus/isolation & purification
Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene

Zain SM, Mohamed Z, Mahadeva S, Cheah PL, Rampal S, Chin KF, et al.

J Gastroenterol Hepatol, 2013 May;28(5):873-9.
PMID: 23278404 DOI: 10.1111/jgh.12104

Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD.

Matched MeSH terms: Disease Susceptibility*; Non-alcoholic Fatty Liver Disease
A hybrid neural network system for pattern classification tasks with missing features

Lim CP, Leong JH, Kuan MM

IEEE Trans Pattern Anal Mach Intell, 2005 Apr;27(4):648-53.
PMID: 15794170

A hybrid neural network comprising Fuzzy ARTMAP and Fuzzy C-Means Clustering is proposed for pattern classification with incomplete training and test data. Two benchmark problems and a real medical pattern classification task are employed to evaluate the effectiveness of the hybrid network. The results are analyzed and compared with those from other methods.

Matched MeSH terms: Acute Disease; Coronary Disease/diagnosis
Fulltext Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

Mamikutty N, Thent ZC, Haji Suhaimi F

Biomed Res Int, 2015;2015:895961.
PMID: 26273656 DOI: 10.1155/2015/895961

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD.
AIMS: In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis.
METHODS: The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph.
RESULTS: After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density.
CONCLUSION: We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.

Matched MeSH terms: Non-alcoholic Fatty Liver Disease/chemically induced*; Non-alcoholic Fatty Liver Disease/pathology*
Test-retest reliability of HeartQoL and its comparability to the MacNew heart disease health-related quality of life questionnaire

Lee WL, Chinna K, Bulgiba A, Abdullah KL, Abidin IZ, Höfer S

Qual Life Res, 2016 Feb;25(2):351-357.
PMID: 26254801 DOI: 10.1007/s11136-015-1097-1

OBJECTIVES: Heart Quality of Life (HeartQoL) is a new "hybrid" developed from the MacNew and two condition-specific questionnaires measuring health-related quality of life (HRQoL) in patients with ischemic heart disease (IHD). This study investigates test-retest reliability of HeartQoL (English version) according to international criteria (e.g., COSMIN, GRRAS). Findings on HeartQoL are compared to the published data on MacNew in view that both serve as the core IHD-specific HRQoL instrument.
METHODS: Out of 105 patients with IHD, 76 completed self-administration of HeartQoL at the clinic followed by at home within a 2-week interval. In retest, patients responded using non-interview methods (phone messaging, email, fax, and post). Phone interviewing was reserved for non-respondents to reminder.
RESULTS: Reliability of HeartQoL was good (intraclass correlation coefficients = 0.78-0.82), was supported in the Bland-Altman plot, and was comparable to five studies on MacNew of similar retest interval (MacNew-English = 0.70-0.75; translated MacNew = 0.72-0.91). Applicability of its standard error of measurement (0.20-0.25) and smallest detectable change (0.55-0.70) will depend on availability of normative data in future.
CONCLUSION: The reliability of HeartQoL is comparable to its parent instrument, the MacNew. The HeartQoL is a potentially reliable core IHD-specific HRQoL instrument in measuring group change.

Matched MeSH terms: Coronary Artery Disease/psychology*; Coronary Artery Disease/therapy
Relation of Dietary Glycemic Index and Glycemic Load to Coronary Artery Calcium in Asymptomatic Korean Adults

Choi Y, Chang Y, Ryu S, Cho J, Kim MK, Ahn Y, et al.

Am J Cardiol, 2015 Aug 15;116(4):520-6.
PMID: 26073677 DOI: 10.1016/j.amjcard.2015.05.005

The relation between glycemic index, glycemic load, and subclinical coronary atherosclerosis is unknown. The aim of the study was to evaluate the associations between energy-adjusted glycemic index, glycemic load, and coronary artery calcium (CAC). This study was cross-sectional analysis of 28,429 asymptomatic Korean men and women (mean age 41.4 years) without a history of diabetes or cardiovascular disease. All participants underwent a health screening examination between March 2011 and April 2013, and dietary intake over the preceding year was estimated using a validated food frequency questionnaire. Cardiac computed tomography was used for CAC scoring. The prevalence of detectable CAC (CAC score >0) was 12.4%. In multivariable-adjusted models, the CAC score ratios (95% confidence intervals) comparing the highest to the lowest quintile of glycemic index and glycemic load were 1.74 (1.08 to 2.81; p trend = 0.03) and 3.04 (1.43 to 6.46; p trend = 0.005), respectively. These associations did not differ by clinical subgroups, including the participants at low cardiovascular risk. In conclusion, these findings suggest that high dietary glycemic index and glycemic load were associated with a greater prevalence and degree of CAC, with glycemic load having a stronger association.

Matched MeSH terms: Coronary Artery Disease/diagnosis; Coronary Artery Disease/epidemiology*
The pattern of lymphoma in east Malaysian patients as experienced in the University Hospital, Kuala Lumpur

Chai SP, Peh SC, Kim LH, Lim MY, Gudum HR

Malays J Pathol, 1999 Jun;21(1):45-50.
PMID: 10879278

Lymphoma is a highly heterogeneous group of malignant disease. This study aimed to elucidate the pattern of lymphoma in the East Malaysian patient population. 107 cases of confirmed lymphomas from East Malaysian biopsy material were retrieved from the files of the Department of Pathology, University of Malaya, in the 3-year period between 1981 to 1983. With the use of a panel of lymphoid antibodies, the disease was sub-classified using the Rye classification for Hodgkin's lymphoma (HL) and the REAL classification for non-Hodgkin's lymphoma (NHL). All of the cases were tested for the presence of the Epstein-Barr virus by EBER-ISH. There were 11 (10.3%) HL, 80 (74.7%) B-NHL and 16 (15%) T-NHL. The HL:NHL ratio was 1:9. The most common tumour in children was Burkitt's lymphoma 7/13 (53.8%). In the adult group, there were 72/94 (76.6%) B-NHL ¿diffuse large cell type 51 (of which 2 were CD30+), Burkitt's lymphoma 8, follicular lymphoma 5, low grade MALT 2, mantle cell type 1 and not otherwise specified due to poor morphology 5¿, 13/94 (13.8%) T-NHL and 9/94 (9.6%) HL. Of the 9 adult HL, the most common subtype was nodular sclerosis (6, 66.7%). The EBER positive rate in classical HL, T-NHL, BL and B-NHL were 33.3%, 56.3%, 60.0% and 3.1% respectively. In conclusion, the spectrum of lymphoma seen in East Malaysia was rather similar to West Malaysia except for the very low prevalence of peripheral T-cell lymphoma (PTCL) in Sarawak (3.3%).

Matched MeSH terms: Hodgkin Disease/epidemiology; Hodgkin Disease/virology
Detection of Legionella pneumophila antigens in patients' sera using monoclonal antibodies

Normaznah Y, Saniah K, Noor Rain A, Norazah A, Azizah MR, Sabiha P

Malays J Pathol, 1998 Dec;20(2):95-8.
PMID: 10879269

Three monoclonal antibodies (McAb) were produced against soluble antigens of Legionella pneumophila serogroup 1 which was cultured on BCYE agar. The McAbs were all of the IgM isotype. The McAbs were used in the McAb-based ELISA for detection of circulating L. pneumophila antigens in 186 sera collected from patients with symptoms and signs suggestive of atypical pneumonia. The normal reference optical (OD) density value of each of the McAbs was determined using 44 sera collected from healthy blood donors. The antigen positivity rates for the McAbs 1C7.2B, 2B2.10F and 2B2.11E were 11.3%, 7.7% and 22.2% respectively. Antigen positivity of the McAb 2B2.10F was significantly higher in the younger age group (p < 0.05). There is no significant association between the antigen positivity with age and sex for all the McAbs. There was no cross-reaction demonstrated between the McAbs with other bacterial antigens.

Matched MeSH terms: Legionnaires' Disease/diagnosis; Legionnaires' Disease/immunology*
Cardiovascular epidemiology in the Asia-Pacific region

Khor GL

Asia Pac J Clin Nutr, 2001;10(2):76-80.
PMID: 11710361

By 2020, non-communicable diseases including cardiovascular diseases (CVD) are expected to account for seven out of every 10 deaths in the developing countries compared with less than half this value today. As a proportion of total deaths from all-causes, CVD in the Asia Pacific region ranges from less than 20% in countries such as Thailand, Philippines and Indonesia to 20-30% in urban China, Hong Kong, Japan, Korea and Malaysia. Countries such as New Zealand, Australia and Singapore have relatively high rates that exceed 30-35%. The latter countries also rank high for coronary heart disease (CHD) mortality rate (more than 150 deaths per 100,000). In contrast, death from cerebrovascular disease is higher among East Asian countries including Japan, China and Taiwan (more than 100 per 100,000). It is worth noting that a number of countries in the region with high proportions of deaths from CVD have undergone marked declining rates in recent decades. For example, in Australia, between 1986 and 1996, mortality from CHD in men and women aged 30-69 years declined by 46 and 51%, respectively. In Japan. stroke mortality dropped from a high level of 150 per 100,000 during the 1920s-1940s to the present level of approximately 100 per 100,000. Nonetheless, CVD mortality rate is reportedly on the rise in several countries in the region, including urban China, Malaysia, Korea and Taiwan. In China, CVD mortality increased as a proportion of total deaths from 12.8% in 1957 to 35.8% in 1990. The region is undergoing a rapid pace of urbanization, industrialization and major technological and lifestyle changes. Thus, monitoring the impact of these changes on cardiovascular risks is essential to enable the implementation of appropriate strategies towards countering the rise of CVD mortality.

Matched MeSH terms: Coronary Disease/mortality; Coronary Disease/epidemiology
From the Centers for Disease Control and Prevention. Update: outbreak of acute febrile illness among athletes participating in Eco-Challenge-Sabah 2000--Borneo, Malaysia, 2000

JAMA, 2001 Feb 14;285(6):728-30.
PMID: 11236770
Matched MeSH terms: Acute Disease; Disease Outbreaks*
Nipah virus--a potential agent of bioterrorism?

Lam SK

Antiviral Res, 2003 Jan;57(1-2):113-9.
PMID: 12615307

Nipah virus, a newly emerging deadly paramyxovirus isolated during a large outbreak of viral encephalitis in Malaysia, has many of the physical attributes to serve as a potential agent of bioterrorism. The outbreak caused widespread panic and fear because of its high mortality and the inability to control the disease initially. There were considerable social disruptions and tremendous economic loss to an important pig-rearing industry. This highly virulent virus, believed to be introduced into pig farms by fruit bats, spread easily among pigs and was transmitted to humans who came into close contact with infected animals. From pigs, the virus was also transmitted to other animals such as dogs, cats, and horses. The Nipah virus has the potential to be considered an agent of bioterrorism.

Matched MeSH terms: Disease Outbreaks*; Disease Reservoirs
Why is acute leukemia more common in males? A possible sex-determined risk linked to the ABO blood group genes

Jackson N, Menon BS, Zarina W, Zawawi N, Naing NN

Ann Hematol, 1999 May;78(5):233-6.
PMID: 10391104

Acute leukemia is more common in males at almost every age, and this fact remains unexplained. A study was carried out in northeast peninsular Malaysia, where the population is predominantly Malay, to examine whether there was a difference in ABO blood group distribution between males and females with acute leukemia (AL). The ABO blood groups of 109 male and 79 female patients with AL (98 ALL, 90 AML) were compared with those of 1019 controls. In the control population, 39.7% were group O. Among males with AL, 39.4% were group O, whereas among females with AL, the proportion was 24.1% (p=0.03). The same trend to a lower proportion of group O among females was seen if the group was divided into adult/pediatric or lymphoblastic/myeloblastic groups, though these differences were not statistically significant. If these findings can be confirmed, they suggest the presence of a "sex-responsive" gene near to the ABO gene locus on chromosome 9, which relatively protects group O women against AL, at least in our population. The existence of such a gene might also partly explain why acute leukemia, and possibly other childhood cancers, are more common in males.

Matched MeSH terms: Genetic Predisposition to Disease/genetics; Genetic Predisposition to Disease/epidemiology
Fulltext Genetic causes of familial hypercholesterolaemia in a Malaysian population

Khoo KL, Van Acker P, Tan H, Deslypere JP

Med J Malaysia, 2000 Dec;55(4):409-18.
PMID: 11221151

A total of 86 unrelated Malaysian patients with familial hypercholesterolaemia (FH) were studied for mutations in their low-density lipoprotein receptor (LDL-R) gene. Amongst them, 23 had a LDL-R gene mutation, while none having an Apolipoprotein B-3500 (Apo B-3500) mutation. Patients with the LDL-R gene defect appeared to have a higher level of low-density lipoprotein cholesterol (LDL-C), an increased incidence of xanthomas and coronary heart disease (CHD), but no relationships were found between the type of LDL-R gene mutations and their lipid levels or clinical signs of CHD. In contrast to Western data, our findings seemed to indicate a predominance of mutations in the ligand binding domain and an absence of Apo B-3500 gene mutation. The latter finding may offer a genetic basis as to why Asian patients with familial hypercholesterolaemia have lower LDL-C levels and less premature CHD than their Western counterparts.

Matched MeSH terms: Coronary Disease/etiology; Coronary Disease/epidemiology
Genetic diversity of enterovirus 71 isolated from cases of hand, foot and mouth disease in Yokohama City between 1982 and 2000

Munemura T, Saikusa M, Kawakami C, Shimizu H, Oseto M, Hagiwara A, et al.

Arch Virol, 2003 Feb;148(2):253-63.
PMID: 12556991

Enterovirus 71 (EV71) is known as one of the major causative agents of hand, foot and mouse disease (HFMD) and is also associated with neurological manifestations such as aseptic meningitis, polio-like paralysis and encephalitis. Recently, large HFMD outbreaks, involving severe neurological complications, have been experienced in Malaysia, Taiwan and some other countries in the Western-Pacific region. To investigate the genetic diversity of EV71 isolates in a single community in Japan, nucleotide sequences of the VP4 region of 52 EV71 isolates in Yokohama City from 1982 to 2000 were determined and the phylogenetic relationship was compared with other referential EV71 strains in Japan and in the world. There were two major genotypes of EV71 in Yokohama City through the 1980's and 1990's. Six EV71 isolates in the early 1980's in Yokohama City were closely related to those from HFMD outbreaks in Japan and from outbreaks of polio-like paralysis in Europe in the 1970's. During recent HFMD outbreaks in 1997 and 2000, two distinct genotypes of EV71 were co-circulating in Yokohama City as in HFMD outbreaks in Malaysia and Taiwan. However, the genetic diversity of EV71 in Yokohama City was not directly correlated with the severity of HFMD. The results confirmed the circulation of two distinct genotypes of EV71 over the past 20 years in Japan.

Matched MeSH terms: Hand, Foot and Mouth Disease/epidemiology; Hand, Foot and Mouth Disease/virology*
Fulltext Vitamins, selenium, iron, and coronary heart disease risk in Indians, Malays, and Chinese in Singapore

Hughes K, Ong CN

J Epidemiol Community Health, 1998 Mar;52(3):181-5.
PMID: 9616423

STUDY OBJECTIVE: To examine the hypothesis that the higher rates of coronary heart disease (CHD) in Indians (South Asians) compared with Malays and Chinese is partly because of differences in antioxidants (vitamins A, C, and E, and selenium) and pro-oxidants (iron).
DESIGN: Cross sectional study of the general population.
SETTING: Singapore.
PARTICIPANTS: Random sample of 941 persons aged 30 to 69 years.
MAIN RESULTS: There were moderate correlations between vitamin A and vitamin E, and between these vitamins and selenium. Mean plasma vitamins A and E were similar by ethnic group. Vitamin A concentration for Indians were (men 0.66 and women 0.51 mg/l), Malays (men 0.67 and women 0.54 mg/l), and Chinese (men 0.68 and women 0.52 mg/l). Vitamin E concentrations for Indians were (men 12.9 and women 12.8 mg/l), Malays (men 13.6 and women 13.3 mg/l), and Chinese (men 12.6 and women 12.6 mg/l). In contrast, mean plasma vitamin C concentrations were lower in Indians (men 5.7 and women 6.9 mg/l) and Malays (men 5.1 and women 6.4 mg/l) than Chinese (men 6.3 and women 8.4 mg/l). Mean serum selenium was lower in Indians (men 117 and women 115 micrograms/l) than Malays (men 122 and women 122 micrograms/l) and Chinese (men 126 and women 119 micrograms/l). Mean serum ferritin was much lower in Indians (men 132 and women 50 micrograms/l) than Malays (men 175 and women 85 micrograms/l) and Chinese (men 236 and women 92 micrograms/l).
MAIN CONCLUSIONS: Lower vitamin C and selenium in Indians, particularly in combination, could play a part in their increased risk of CHD. Vitamins A and E, and ferritin (iron) have no such role. Lower vitamin C in Indians and Malays is probably because of its destruction by more prolonged cooking. In Indians, lower selenium is probably because of a lower dietary intake and the much lower ferritin to a lower dietary intake of iron and its binding by phytates.

Matched MeSH terms: Coronary Disease/ethnology; Coronary Disease/etiology*
Insulin-like growth factor-binding protein-3 (IGFBP-3) but not insulin-like growth factor-I (IGF-I) remains elevated in euthyroid TSH-suppressed Graves' disease

Wan Nazaimoon WM, Khalid BA

Horm. Metab. Res., 1998 Apr;30(4):213-6.
PMID: 9623636 DOI: 10.1055/s-2007-978868

Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.

Matched MeSH terms: Graves Disease/blood; Graves Disease/physiopathology*
Microcalcification clustering parameters in breast disease: a morphometric analysis of radiographs of excision specimens

Ng KH, Looi LM, Bradley DA

Br J Radiol, 1996 Apr;69(820):326-34.
PMID: 8665132

X-ray microradiography of surgically excised breast specimens offers the possibility of morphological characterization of calcifications. When combined with digital imaging techniques there exists added potential for obtaining valuable basic quantitative morphometric information regarding differences between microcalcifications in tissues exhibiting evidence of fibrocystic change, benign and malignant tumours. A total of 157 excised breast specimens from 84 patients were microradiographed using a Softex Super Soft X-ray unit and Kodak AA high resolution industrial film. A Quantimet 570C image analysis system was used to digitize and analyse the microradiographs. Of the 157 microradiographs, 51 (from 30 patients) revealed microcalcification clusters. The existence of significant differences between the three identified categories of tissue were indicated by clustering parameters. These included the number of particles per cluster, area of clusters, maximum distance to nearest neighbour, and geometric mean distance to nearest neighbour. The distribution pattern index (DPI), another of the clustering parameters used in this study, has been observed to be a particularly powerful discriminator. The value for fibrocystic change was found to be significantly smaller (0.514) than that for benign tumour (0.796) whilst that for benign tumour was observed to be significantly larger than that for malignant tumour (0.604) at a p-value of less than 0.05 (Kruskal-Wallis one-way analysis of variance).

Matched MeSH terms: Fibrocystic Breast Disease/complications; Fibrocystic Breast Disease/radiography*

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